PMID- 17719265 TI - Role of phages in the pathogenesis of Burkholderia, or 'Where are the toxin genes in Burkholderia phages?'. AB - Most bacteria of the genus Burkholderia are soil- and rhizosphere-associated, and rhizosphere associated, noted for their metabolic plasticity in the utilization of a wide range of organic compounds as carbon sources. Many Burkholderia species are also opportunistic human and plant pathogens, and the distinction between environmental, plant, and human pathogens is not always clear. Burkholderia phages are not uncommon and multiple cryptic prophages are identifiable in the sequenced Burkholderia genomes. Phages have played a crucial role in the transmission of virulence factors among many important pathogens; however, the data do not yet support a significant correlation between phages and pathogenicity in the Burkholderia. This may be due to the role of Burkholderia as a 'versaphile' such that selection is occurring in several niches, including as a pathogen and in the context of environmental survival. PMID- 17719266 TI - Hypervariation and phase variation in the bacteriophage 'resistome'. AB - Most bacteria encode proteins for defence against infection by bacteriophages. The mechanisms that bring about phage defence are extremely diverse, suggesting frequent independent evolution of novel processes. Phage defence determinants are often plasmid or phage-encoded and many that are chromosomal show evidence of lateral transfer. Recent studies on restriction-modification (R-M) systems show that these genes are amongst the most rapidly evolving. Some bacteria have contingency genes that encode alternative target specificity determinants for Type I or Type III R-M systems, thus expanding the range of phages against which the host population is immune. The most counter-intuitive observation, however, is the prevalence of phase variation in many restriction systems, but recent arguments suggest that switching off expression of R-M systems can aid phage defence. PMID- 17719268 TI - Multiwavelength spectrophotometric determination of acidity constants of some azo dyes. AB - A multiwavelength spectrophotometric titration method was applied to study the acidity constants of some azo dyes in water. The UV-vis absorption spectra of azo dye solutions were recorded in the course of their pH-metric titration with a standard base solution. The protolytic equilibrium constants, spectral profiles, concentration diagrams and also the number of components have been calculated. The quantitative effects of the substituents on the acidity of the studied azo dyes were investigated by the linear free energy relationship (LFER) using Hammet sigma constant (sigma) and field and resonance effects of Kamlet and Taft (f and Re, respectively). PMID- 17719267 TI - Dimorphism and virulence in fungi. AB - The signature feature of systemic dimorphic fungi - a family of six primary fungal pathogens of humans - is a temperature-induced phase transition. These fungi grow as a mold in soil at ambient temperature and convert to yeast after infectious spores are inhaled into the lungs of a mammalian host. Seminal work 20 years ago established that a temperature-induced phase transition from mold to yeast is required for virulence. Several yeast-phase specific genes, identified one-by-one and studied by reverse genetics, have revealed mechanisms by which the phase transition promotes disease pathogenesis. Transcriptional profiling of microarrays built with genomic elements of Histoplasma capsulatum and ESTs of Paracoccidioides brasiliensis that represent partial genomes has identified 500 genes and 328 genes, respectively, that are differentially expressed upon the phase transition. The genomes of most of the dimorphic fungi are now in varying stages of being sequenced. The creation of additional microarrays and the application of new reverse genetic tools promise fresh insight into genes and mechanisms that regulate pathogenesis and morphogenesis. The use of insertional mutagenesis by Agrobacterium has uncovered a hybrid histidine kinase that regulates dimorphism and pathogenicity in Blastomyces dermatitidis and H. capsulatum. Two-component signaling appears to be a common strategy for model and pathogenic fungi to sense and respond to environmental stresses. PMID- 17719269 TI - Study on the binding of luteolin to bovine serum albumin. AB - Binding of luteolin (LU) to bovine serum albumin (BSA) was investigated at 298, 308 and 318K at pH 7.4 using spectrophotometric techniques such as fluorescence emission, circular dichroism (CD). The data obtained from fluorescence quenching experiments showed that LU was bound to BSA and binding constants and the number of binding sites (n approximately 1) were obtained. The thermodynamic parameters DeltaH(0), DeltaS(0), DeltaG(0) at different temperatures were calculated. They indicated that both hydrophobic forces and hydrogen bonds are the major interactions between LU and BSA. A value of 3.12nm for the average distance r between LU (acceptor) and tryptophan residue (Trp) of BSA (donor) was derived from the fluorescence resonance energy transfer. The effects of some common metal ions on the binding are also considered. Besides, the interaction of BSA with LU led to a change in the conformation of BSA. PMID- 17719270 TI - Brain magnetic resonance imaging abnormalities in patients with heart failure. AB - BACKGROUND: Although heart failure (HF) is a common cardiovascular disorder, to date little research has been conducted into possible associations between HF and structural abnormalities of the brain. AIMS: To determine the frequency and pattern of magnetic resonance imaging (MRI) abnormalities in outpatients with chronic HF, and to identify any demographic and clinical correlates. METHODS: Brain MRI scans were compared between a sample of 58 HF patients, 48 controls diagnosed with cardiovascular disease uncomplicated by HF (cardiac controls) and 42 healthy controls. Deep, periventricular and total white matter hyperintensities (WMH), lacunar and cortical infarcts, global and medial temporal lobe atrophy (MTA) were investigated. RESULTS: Compared to cardiac and healthy controls, HF patients had significantly more WMH, lacunar infarcts and MTA, whereas cardiac controls only had more MTA, compared to healthy controls. Age and left ventricular ejection fraction (LVEF) were independently associated with total WMH. Age and systolic hypotension were associated with MTA in HF patients and cardiac controls. CONCLUSION: Our results suggest that cardiac dysfunction contributes independently to the development of cerebral MRI abnormalities in patients with HF. Age and low LVEF are the principal predictors of cerebral WMH in patients with HF and in cardiac controls. PMID- 17719271 TI - LV systolic impairment in patients with asymptomatic coronary heart disease and type 1 diabetes is related to coronary atherosclerosis, glycaemic control and advanced glycation endproducts. AB - AIMS: To evaluate whether heart failure in type 1 diabetes is linked to poor glycaemic control, coronary atherosclerosis or advanced glycation endproducts (AGEs). METHODS: Twenty six patients with type 1 diabetes (mean duration 32+/-5 years), and 16 age matched controls were recruited. Mean HbA(1c) through 18 years (HbA(1c)18), serum levels of AGEs and coronary atherosclerotic burden (CAB) were determined by IVUS. Peak tissue velocities and strain by tissue Doppler imaging were measured in 12 LV regions as an evaluation of LV function. RESULTS: Systolic tissue velocity was inversely correlated to CAB (r=0.53, p<0.01), to HbA(1c)18 (r=0.46, p<0.05) and to the duration of diabetes (r=0.46, p<0.05). Systolic strain was inversely correlated to HbA(1c)18 (r=0.45, p<0.05), to duration of diabetes (r=0.41, p<0.05), and tended to correlate with AGEs (r=0.37, p=0.07). In multiple regression analyses, CAB and HbA(1c)18 were significant independent predictors for systolic velocity, while AGEs and duration of diabetes were significant predictors of systolic strain. CONCLUSION: LV systolic function was impaired by increasing coronary atherosclerosis and worsening of glycaemic control. AGEs might be another mechanism for the increased risk of heart failure in type 1 diabetes. PMID- 17719272 TI - Reactive oxygen species in the paraventricular nucleus mediate the cardiac sympathetic afferent reflex in chronic heart failure rats. AB - The aim of this study was to determine whether reactive oxygen species (ROS) in the paraventricular nucleus (PVN) mediate both the cardiac sympathetic afferent reflex (CSAR) and angiotensin II-induced CSAR enhancement in chronic heart failure (CHF) rats. CSAR was evaluated from the responses of renal sympathetic nerve activity (RSNA) to epicardial application of bradykinin. In both CHF and sham-operated rats, PVN microinjection of the superoxide anion scavengers tempol or tiron almost abolished the CSAR, but the superoxide dismutase inhibitor DETC potentiated the CSAR. PVN pretreatment with tempol or tiron abolished, whereas DETC augmented, the angiotensin II-induced CSAR enhancement. In CHF rats, superoxide anion and malondialdehyde (MDA) levels in the PVN were increased, but were normalized by the AT(1) receptor antagonist losartan. PVN microinjection of tempol decreased superoxide anion and MDA levels, but epicardial application of bradykinin or PVN microinjection of angiotensin II increased superoxide anion and MDA to higher levels in CHF rats than in sham-operated rats. These results indicate that ROS in the PVN mediates the CSAR and the effect of angiotensin II in the PVN on the CSAR in both CHF and sham-operated rats. Increased ROS in the PVN are involved in the enhanced CSAR in CHF. PMID- 17719273 TI - Relation between dose of loop diuretics and outcomes in a heart failure population: results of the ESCAPE trial. AB - BACKGROUND: We examined the relation of maximal in-hospital diuretic dose to weight loss, changes in renal function, and mortality in hospitalised heart failure (HF) patients. METHODS: In ESCAPE, 395 patients received diuretics in hospital. Weight was measured at baseline, discharge, and every other day before discharge. Weight loss was defined as the difference between baseline and last in hospital weight. Mortality was assessed using a log-logistic model with non-zero background. RESULTS: Median weight loss: 2.8 kg (0.7, 6.1); mean: 3.7 kg (22% of values <0). Weight loss and maximum in-hospital dose were correlated (p=0.0007). Baseline weight, length of stay, and baseline brain natriuretic peptide were significant predictors of weight loss. After adjusting for these, dose was not a significant predictor of weight loss. A strong relation between dose and mortality was seen (p=0.003), especially at >300 mg/day. Dose remained a significant predictor of mortality after adjusting for baseline variables that significantly predicted mortality. Correlation between maximal dose and creatinine level change was not significant (r=0.043; p=0.412) CONCLUSIONS: High diuretic doses during HF hospitalisation are associated with increased mortality and poor 6-month outcome. PMID- 17719274 TI - Mechanisms of dendritic cell-based vaccination against infection. AB - Due to their unique capacity to initiate and regulate adaptive immune responses, dendritic cells (DC) represent the most potent antigen-presenting cells of the immune system. Immature DC reside in peripheral tissues, where they sample and process antigens and efficiently sense a large variety of signals from the surrounding environment. Toll-like receptors (TLR) expressed by DC play a critical role in the detection of invading pathogens as well as in triggering the subsequent immune responses. The differential expression of TLR by different DC subsets may correlate with the induction of different patterns of adaptive immune responses. The rapidly expanding and fundamental knowledge of DC biology furthers promising perspectives for the development of vaccination strategies in different fields. For example, the immunotherapeutic potential of antigen-pulsed DC for the treatment of cancer has been confirmed in a number of experimental tumour models. Furthermore, DC have been shown to serve as natural adjuvants in different models of infectious diseases, mediating protection against various types of pathogens. Using murine leishmaniasis as an example, we have demonstrated that DC, once properly conditioned ex vivo, mediate complete and durable protection against infection. Critical parameters determining the efficiency of DC-based vaccination against microbial pathogens include the origin of DC, the choice of antigen to be used for DC loading, the route of immunization and the state of DC maturation and activation. In the present review, we discuss the necessity to define the mechanisms responsible for the immunostimulatory capacity of DC in vivo, in order to exploit their full potential as vaccination tools. PMID- 17719275 TI - Salmonella type III-mediated heterologous antigen delivery: a versatile oral vaccination strategy to induce cellular immunity against infectious agents and tumors. AB - Salmonella type III secretion system (T3SS)-mediated translocation can be used for efficient delivery of heterologous antigens to the cytosol of antigen presenting cells leading to prominent CD8 T-cell priming in orally immunized mice. The time point and duration of hybrid protein translocation during the Salmonella infection cycle can be modulated by employing various type III carrier molecules. The p60 protein of Listeria monocytogenes was used as model antigen to construct chimeric SspH2/p60. SspH2 is a "Salmonella pathogenicity island 2" (SPI2) protein that is known to be translocated by Salmonella during intracellular survival and replication in macrophages. This SPI2 carrier molecule is sufficient to induce a concomitant p60-specific CD4 and CD8 T-cell response in Salmonella-vaccinated mice. Moreover, T3SS-mediated antigen delivery results in an efficient priming of central and effector memory CD8 T cells in spleens of these animals. This vaccination strategy can also be employed to efficiently protect mice from an aggressive fibrosarcoma transfected with p60 in a prophylactic setting. PMID- 17719276 TI - Half-truths and selective memory: Interferon gamma, CD4(+) T cells and protective memory against tuberculosis. AB - Efforts to develop a new, more effective vaccine for tuberculosis have been hampered by a lack of understanding of what constitutes a protective memory immune response. While interferon gamma production by CD4(+) T cells after vaccination is commonly used as a surrogate of protective memory immunity, its use in this regard appears to have little predictive value. We argue that this is due to the different requirements for interferon gamma-mediated protection in the primary response versus the memory recall response. In this review, we present evidence that suggests memory CD4(+) T cells can protect against tuberculosis in the absence of interferon gamma, and discuss potential mechanisms that may be involved such as IL-17 and regulatory T cells. A comprehensive understanding of the requirements for protective memory immunity to tuberculosis is essential for the development of an effective vaccine. PMID- 17719277 TI - Genome analysis shows a common evolutionary origin for the dominant strains of Mycobacterium tuberculosis in a UK South Asian community. AB - We have investigated the Mycobacterium tuberculosis strain types present in the South Asian population of the UK, in which tuberculosis is particularly prevalent. In contrast to the widespread Beijing strains which have the variable number tandem repeats (VNTR) profile 42435, isolates with the VNTR profile 42235, jointly with 02335 or 42234 profiles, appear more frequently in tuberculosis patients of South Asian ethnic origin (SA-strains) in the UK than in any other ethnic group. Using microarray-based comparative genomics to distinguish total or partially deleted genes, we found that three of the common deleted regions in the SA-strains were identical to some deleted genes in the strain CH, which caused an outbreak among South Asian patients in Leicester in 2001 but were different from genomic deletions found in Beijing/W strains. Analysis of some of the deleted regions revealed differences in comparison to the strain CH including the polymorphism in some of the PE/PPE and Esat-6 genes, which may be responsible for the diversity of antigenic variation or differences in the activation of the host immune response. Interrupted genes or the replacement by insertion elements was confirmed in some of the deleted genomic regions. Our results are consistent with the hypothesis that the SA-strains may present common features, implying a common origin for this group of strains. PMID- 17719278 TI - Purification and isolation of corticosteroidogenic cells from head kidney of rainbow trout (Oncorhynchus mykiss) for testing cell-specific effects of a pesticide. AB - The teleost head kidneys contain corticosteroidogenic cells, chromaffin cells, lymphoid cells, and melanomacrophages. We have developed and validated a method using a Percoll density gradient and differential staining for 3beta hydroxysteroid dehydrogenase (3beta-HSD) to prepare fractions enriched with specific head kidney cell types. The proportion of steroidogenic cells to other cells in the head kidney was 1:8000 in rainbow trout, Oncorhynchus mykiss. To test the hypothesis that steroidogenic cells are more vulnerable to a pesticide than other cell types in the head kidney, head kidney cells were separated by a Percoll gradient and the steroidogenic cell-enriched fractions and lymphoid cell enriched fractions were exposed to the pesticide endosulfan in vitro, and their functional integrity and viability were assessed. The effective concentration of the pesticide (EC50, concentration that inhibits 50% of the secretory response to ACTH) in the mixed head kidney cell preparation was similar to the EC50 in the fraction enriched with steroidogenic cells, but differences in viability were detected. The Percoll method for isolation of different cell types from the head kidney facilitated a study of cell-specific effects of a pesticide. PMID- 17719279 TI - Validation of the Italian version of the Cystic Fibrosis Quality of Life Questionnaire (CFQoL), a disease specific measure for adults and adolescents with cystic fibrosis. AB - BACKGROUND: Disease specific, health-related quality of life (HRQoL) measurement is important in cystic fibrosis (CF). This work aimed to translate the original English Cystic Fibrosis Quality of Life Questionnaire (CFQoL) into Italian, evaluate the linguistic translation and to psychometrically evaluate the Italian version of the CFQoL. METHODS: The linguistic translation followed the international guidelines of forward and backward translation. Psychometric evaluation of the Italian CFQoL involved the assessment of construct validity, internal reliability, concurrent validity, known groups validity and test-retest reliability. RESULTS: The instrument was acceptable to adolescents and adults with CF and demonstrated robust psychometric properties. Principle components analysis indicated that the factorial structure was essentially similar to the original, and the internal reliability of each domain was good (Cronbach alpha coefficients 0.73 to 0.91). Appropriate domains of the CFQoL and SF-36 correlated well indicating good concurrent validity (r=0.68-0.80). Consistent with theoretical expectations some domains were able to discriminate between disease severity groups. Test-retest reliability, assessed by intraclass correlation coefficients, was found to be excellent (ICC 0.83 to 0.98). CONCLUSIONS: The Italian CFQoL is a valid and reliable measure. Its use in individual patient monitoring and research should complement traditional clinical outcome measures. PMID- 17719280 TI - Simultaneous determination of seven nitroimidazole residues in meat by using HPLC UV detection with solid-phase extraction. AB - A method was developed for the determination of the seven nitroimidazoles including metronidazole (MNZ), ronidazole (RNZ), dimetridazole (DMZ), tinidazole (TNZ), ornidazole (ONZ), secnidazole (SNZ) and the common metabolite of RNZ and hydroxydimetridazole (DMOHZ) in poultry and pork muscles by high-performance liquid chromatography (HPLC) with ultraviolet detection (UV). After extraction with ethyl acetate and evaporation, the nitroimidazoles were redissolved in ethyl acetate and purified using strong cation exchange (SCX) solid-phase extraction (SPE) column. The HPLC separation was carried through on a C(18) bonded silica column with a deionized water-methanol-acetonitrile mobile phase using a gradient elution procedure. The limit of detection of all the seven nitroimidazoles was 0.2 microg/kg. The recoveries of the seven nitroimidazoles for chicken, pork and bacon samples spiked with 1-20 microg/kg were in the range of 71.4-99.5%. The linearity is satisfactory with a correlation coefficient of >0.998 at concentrations ranging from 0.7 to 60 microg/kg. The relative standard deviations of 10 measurements for spiked chicken, pork and bacon samples at the concentration of 1 and 20 microg/kg were in the range of 6.2-13.9% and 4.0-8.7%, respectively. The intra-day precision (n=5) for nitroimidazoles residues in chicken spiked at 20 microg/kg is 6.9%, and the inter-day precision for 5 days (n=25) is 11%. The method is capable of identifying nitroimidazole residues at > or =0.7 microg/kg levels and was applied in the determination of nitroimidazole residues in meat sample. PMID- 17719281 TI - Is there any hope for angiotensin-converting enzyme inhibitors in atrial fibrillation? PMID- 17719282 TI - Perioperative use of cardiac medical therapy among patients undergoing coronary artery bypass graft surgery: a systematic review. AB - BACKGROUND: The use of perioperative cardiac medical therapy among patients undergoing coronary artery bypass graft surgery (CABG) has not been closely examined. OBJECTIVES: The objective of this study was to systematically review the medical literature examining the effects of perioperative cardiac medical therapy on clinical outcomes among patients undergoing CABG. METHODS: Using the Medline database and online clinical trial databases, we reviewed all randomized controlled trials (RCTs) and observational studies examining the effect of perioperative angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, antilipid agents (including statins), aspirin, beta-blockers, and calcium-channel blockers on clinical outcomes. RESULTS: Our review identified 27 studies (6 RCTs, 21 observational studies), involving >700,000 patients, that examined the impact of perioperative medical therapy on clinical outcomes after CABG. Although studies provide conflicting results, the literature suggests that perioperative aspirin use may decrease inhospital mortality and myocardial infarction, whereas perioperative angiotensin-converting enzyme inhibitor use does not appear to be beneficial. Perioperative statin use reduces all-cause mortality at 30 days and cardiac death at 60 days and 1 year post-CABG but does not appear to reduce myocardial infarction or congestive heart failure rates. Multiple studies have demonstrated that pre- and postoperative beta-blockers are associated with a decrease in atrial fibrillation. In addition, beta-blockers may reduce inhospital and 30-day mortality, although these results are not consistent across all studies. Calcium-channel blockers do not appear to improve inhospital or 30-day mortality. No studies examined the perioperative use of angiotensin II receptor blockers or nonstatin antilipid agents among CABG patients. CONCLUSIONS: The perioperative use of cardiac medical therapy among CABG patients remains understudied. Given their proven benefits among patients with cardiovascular disease and their potential to improve outcomes among CABG patients, further studies, particularly large RCTs, are needed. PMID- 17719283 TI - Stress echocardiography, stress single-photon-emission computed tomography and electron beam computed tomography for the assessment of coronary artery disease: a meta-analysis of diagnostic performance. AB - BACKGROUND: Many studies have been published on the diagnostic performance of noninvasive tests for the assessment of coronary artery disease. The objective of the present study was to compare the published literature on the diagnostic performance of stress echocardiography, stress single-photon-emission computed tomography (SPECT), and electron beam computed tomography (EBCT). METHODS: Meta analytic studies on the diagnostic performance of imaging tests for coronary artery disease were searched in the Cochrane Library, PubMed, and bibliographies of selected articles. Sensitivities, specificities, and diagnostic odds ratios of the source studies were calculated per modality. Taking into account differences between studies, a random effects summary receiver operating characteristic analysis was performed. RESULTS: We analyzed the data of 351 patient series, which were reported in 11 meta-analyses. The sensitivity of EBCT was significantly higher than that of stress SPECT, which had a significantly higher sensitivity than stress echocardiography (respectively, 93.1% [95% confidence interval, 90.7-95.6], 88.1 [95% confidence interval, 86.6-89.6], and 79.1% [95% confidence interval, 77.6-80.5]). The specificity of stress echocardiography was significantly higher than that of stress SPECT, which had a significantly higher specificity than EBCT (respectively, 87.1% [95% confidence interval, 85.7-88.5], 73.0% [95% confidence interval, 69.1-76.9], and 54.5% [95% confidence interval, 45.3-63.8]). The diagnostic odds ratios did not differ significantly between the 3 modalities, which resulted in one underlying summary receiver operating characteristic curve. CONCLUSIONS: This study suggests that there are no significant differences in the overall diagnostic performance between stress echocardiography, stress SPECT, and EBCT for the diagnosis of coronary artery disease. However, differences exist in sensitivity and specificity estimates, which may make each modality useful in different settings. PMID- 17719284 TI - Cognitive influences on self-care decision making in persons with heart failure. AB - BACKGROUND: Despite advances in management, heart failure is associated with high rates of hospitalization, poor quality of life, and early death. Education intended to improve patients' abilities to care for themselves is an integral component of disease management programs. True self-care requires that patients make decisions about symptoms, but the cognitive deficits documented in 30% to 50% of the heart failure population may make daily decision making challenging. After describing heart failure self-care as a naturalistic decision making process, we explore cognitive deficits known to exist in persons with heart failure. Problems in heart failure self-care are analyzed in relation to neural alterations associated with heart failure. As a neural process, decision making has been traced to regions of the prefrontal cortex, the same areas that are affected by ischemia, infarction, and hypoxemia in heart failure. Resulting deficits in memory, attention, and executive function may impair the perception and interpretation of early symptoms and reasoning and, thereby, delay early treatment implementation. CONCLUSIONS: There is compelling evidence that the neural processes critical to decision making are located in the same structures that are affected by heart failure. Because self-care requires the cognitive ability to learn, perceive, interpret, and respond, research is needed to discern how neural deficits affects these abilities, decision-making, and self-care behaviors. PMID- 17719285 TI - A randomized comparison of sirolimus-eluting stent implantation with zotarolimus eluting stent implantation for the treatment of total coronary occlusions: rationale and design of the PRImary Stenting of Occluded Native coronary arteries III (PRISON III) study. AB - Primary intracoronary drug-eluting stent placement after the successful crossing of total coronary occlusions decreases restenosis rate at long-term follow-up compared with bare-metal stent implantation. The PRISON II trial was the first randomized study to show the safety and efficacy of sirolimus-eluting stents in patients with totally occluded native coronary arteries. The sirolimus-eluting stent is superior to the bare-metal stent in treating patients with total coronary occlusions, with significant reduction in angiographic binary in-stent and in-segment restenosis resulting in significantly reduced need for target lesion and target vessel revascularization. Whether sirolimus-eluting stents are superior to other drug-eluting stents in total coronary occlusions is unknown. In this prospective, randomized trial, sirolimus-eluting stent implantation will be compared with zotarolimus-eluting stent implantation for the treatment of total coronary occlusions. A total of 300 patients will be followed for up to 5 years with angiographic follow-up at 8 months. Quantitative coronary analysis will be performed by an independent core laboratory. The primary end point will be in segment late luminal loss at 8 months angiographic follow-up. PMID- 17719286 TI - Left ventricular remodeling and change of systolic function after closure of patent ductus arteriosus in adults: device and surgical closure. AB - BACKGROUND: Left ventricular (LV) remodeling and predictors of LV systolic function late after closure of patent ductus arteriosus (PDA) in adults remain to be clearly demonstrated. METHODS: In 45 patients with PDA, including 28 patients who received successful occlusion using the Amplatzer device (AD group) (AGA, Golden Valley, MN) and 17 patients who received surgical closure (OP group), echocardiography studies were performed before closure and 1 day (AD group) or within 7 days (OP group) after closure, and then were repeated at > or = 6 months (17 +/- 13 months). RESULTS: In both groups, LV ejection fraction (EF) and end diastolic volume index were significantly decreased immediately after closure, whereas end-systolic volume index did not change. During the long-term follow-up period, end-systolic as well as end-diastolic volume indices decreased significantly in both groups and LV EF recovered compared to the immediate postclosure state. However, LV EF remained low compared to the preclosure state. Five patients (11.1%) including 3 patients in the AD group and 2 patients in the OP group showed persistent late LV systolic dysfunction (EF <50%). In stepwise, multiple logistic regression analysis, preclosure EF was the only independent predictor of late normal postclosure EF (odds ratio, 1.230; 95% CI, 1.054-1.434; P = .008). Receiver operating characteristic curve analysis showed that preclosure EF > or = 62% had a sensitivity of 72% and a specificity of 83% for predicting late normal LV EF after closure. CONCLUSIONS: Left ventricular EF remains low late after PDA closure compared with preclosure state in adults. Preclosure LV EF is the best index to predict late postclosure LV EF. PMID- 17719287 TI - Strong and independent prognostic value of peak circulatory power in adults with congenital heart disease. AB - BACKGROUND: The identification of patients with adult congenital heart disease (ACHD) who are at higher risk of death is challenging. Peak circulatory power (CircP; expressed as peak exercise oxygen uptake multiplied for peak mean arterial blood pressure) is a strong predictor of death in adults with acquired heart disease. We sought to establish the distribution and the prognostic value of peak CircP across a wide spectrum of patients with ACHD. METHODS: Four hundred thirty-two consecutive patients with ACHD of varying diagnosis underwent cardiopulmonary exercise testing at a single laboratory between 1996 and 2005. Patient age was 32 +/- 10 years. RESULTS: A gradual variation in peak CircP was found across the spectrum of congenital heart defects (P < .0001 at analysis of variance). Reduced peak CircP values were associated with the presence of heart failure symptoms (P < .0001), absence of sinus rhythm (P = .010), and use of antiarrhythmic medications (P = .0013). At a follow-up of 4.4 +/- 2.4 years, 23 patients (5.3%) had died. Peak CircP was a strong predictor of mortality when univariate analysis was used and the strongest independent predictor of mortality among exercise parameters. A peak CircP < or = 1476 mm Hg mlO2 min(-1) kg(-2) was associated with a 15.4-fold increase in the 4-year risk of death. CONCLUSIONS: Peak CircP is abnormal across the spectrum of ACHD. Peak CircP appears as the strongest predictor of adverse outcome in ACHD. PMID- 17719288 TI - Impact of ramipril on the incidence of atrial fibrillation: results of the Heart Outcomes Prevention Evaluation study. AB - OBJECTIVES: We evaluated the effect of angiotensin-converting enzyme (ACE) inhibitor ramipril on the incidence of atrial fibrillation (AF) in patients enrolled in the Heart Outcomes Prevention Evaluation trial. BACKGROUND: Atrial fibrillation is the most common arrhythmia affecting the general population and is associated with increased morbidity and mortality. Retrospective secondary analyses of some of the large trials of ACE inhibitors have suggested that ACE inhibitors may prevent AF. METHODS: We evaluated the occurrence of AF by reviewing the electrocardiogram tracings at entry, at 2 years, and at the end of the study, as well as hospitalizations among 8335 high-risk participants from the Heart Outcomes Prevention Evaluation study, > or = 55 years, without known heart failure or left ventricular (LV) systolic dysfunction and followed for a median period of 4.5 years. We compared the impact of ramipril and matched placebo on occurrence of AF. The results were compared to similar trials. RESULTS: Over the 4.5 years follow-up, the incidence of new AF was low (2.1%, 177/8335), and ramipril did not significantly reduce the rate of new AF compared with placebo (86/4291 [2.0%] vs 91/4044 [2.2%]) with an odds ratio of 0.92 (95% confidence interval, 0.68-1.24; P = .57). These results added to the previous ACE inhibitor trials (excluding trials in patients with LV dysfunction) showed no significant reduction in new AF among patients treated with these agents (1088/20,930 [5.0%] vs 1343/22,878 [5.9%]; relative risk, 0.92; 95% confidence interval, 0.80-1.05). CONCLUSION: Although the incidence of AF was low, treatment with ramipril in this population without known LV systolic dysfunction did not significantly reduce this dysrhythmia. PMID- 17719289 TI - Implications of family history of myocardial infarction in young women. AB - BACKGROUND: Family history of premature myocardial infarction (FHMI) may be a useful marker of cardiovascular disease (CVD) risk in young subjects, but comparisons of its implications for CVD risk factor burden, prevalent atherosclerosis, and risk awareness between young men and women have not been reported. METHODS: We analyzed data from 2404 young subjects with ages 30 to 50 in the Dallas Heart Study, which is a population-based study. Family history of premature MI was defined as a first-degree relative with myocardial infarction (MI) before age 50 (men) or 55 (women). Coronary artery calcification was measured by computed tomography scan, and perceived lifetime risk of MI was assessed by questionnaire. Analyses were sex-stratified. RESULTS: Women with versus without FHMI had an increased composite risk factor burden (> or = 2 CVD risk factors, 49.1% vs 39.1%; P < .001), an association not seen in men (P = .6). Family history of premature MI was independently associated with coronary artery calcification among women (adjusted odds ratio, 2.0; 95% confidence interval, 1.0 4.1) but not among men (adjusted odds ratio, 1.7; 95% confidence interval, 0.9 3.2). A higher proportion of subjects with FHMI versus no FHMI perceived their lifetime risk of MI to be at > or = average in women (59.7% vs 47.4%; P < .001) and men (75.0% vs 48.3%; P = .004), with the increment greatest among men (P interaction = .02). CONCLUSIONS: Despite a stronger association with CVD risk factors and atherosclerosis prevalence with FHMI among young women compared with men, young women with FHMI demonstrated less CVD risk awareness and worse lifestyle choices. Family history of premature MI may be an especially useful risk assessment tool in young women, and greater efforts are needed to promote CVD risk awareness among young women with FHMI. PMID- 17719290 TI - Heart rate recovery is more strongly associated with the metabolic syndrome, waist circumference, and insulin sensitivity in women than in men among the elderly in the general population. AB - BACKGROUND: Low heart rate recovery (HRR) at exercise test and the metabolic syndrome (MetS) are both predictors of cardiovascular morbidity and mortality. We studied in 75-year-old women and men, representative of the general population, the relationship between (1) HRR and the MetS, (2) HRR and the individual components of the MetS, and (3) HRR and insulin sensitivity. METHODS: A cross sectional study of randomly selected 75-year-olds from a general population was performed (191 women and 194 men). The MetS was defined according to the National Cholesterol Education Program criteria. Heart rate was measured as beats per minute immediately after exercise and at 4 minutes into recovery. RESULTS: Heart rate recovery (median and interquartile range, beat/min) was 48 (37-58) for women and 49 (38-58) for men. Thirty-seven percent of the women and 25% of the men had the MetS. Heart rate recovery was 52 (42-61) for women with the MetS and 42 (31 49) for those without. The corresponding values for men was 50 (39-61) and 47 (35 54); the difference between individuals with and without the MetS was significant for women (P < .001) but not for men (P = .084). The following significant correlation coefficients between HRR and MetS components were found: for women, waist circumference (-0.43, P < .001), high-density lipoprotein cholesterol (0.37, P < .001), insulin sensitivity (-0.37, P < .001), fasting plasma glucose ( 0.30, P < .001), and triglycerides (-0.24, P = .001); for men, triglycerides ( 0.20, P = .005). The sex disparity in the strength of correlation reached statistical significance for insulin sensitivity (P < .001) and waist circumference (P = .042). CONCLUSION: Among 75-year-olds, the MetS and related components are more strongly correlated to HRR in women than in men. PMID- 17719291 TI - The association between guideline-based treatment instructions at the point of discharge and lower 1-year mortality in Medicare patients after acute myocardial infarction: the American College of Cardiology's Guidelines Applied in Practice (GAP) initiative in Michigan. AB - BACKGROUND: The American College of Cardiology's Guidelines Applied in Practice (GAP) initiative for acute myocardial infarction (AMI) has been shown to increase the use of guideline-based therapies and improve outcomes in patients with AMI. It is unknown whether hospitals that are more successful in using the standard discharge contract--a key component of GAP that emphasizes guideline-based medications, lifestyle modification, and follow-up planning--experience a proportionally greater improvement in patient outcomes. METHODS: Medicare patients treated for AMI in all 33 participating GAP hospitals in Michigan were enrolled. We aggregated the hospitals into 3 tertiles based on the rates of discharge contract use: 0% to 8.4% (tertile 1), >8.4% to 38.0% (tertile 2), and >38.0% to 61.1% (tertile 3). We analyzed 1-year follow-up mortality both pre- and post-GAP and compared the mortality decline post-GAP with discharge contract use according to tertile. RESULTS: There were 1368 patients in the baseline (pre-GAP) cohort and 1489 patients in the post-GAP cohort. After GAP implementation, mortality at 1 year decreased by 1.2% (P = .71), 1.2% (P = .68), and 6.0% (P = .03) for tertiles 1, 2, and 3, respectively. After multivariate adjustment, discharge contract use was significantly associated with decreased 1-year mortality in tertile 2 (odds ratio 0.43, 95% CI 0.22-0.84) and tertile 3 (odds ratio 0.45, 95% CI 0.27-0.75). CONCLUSIONS: Increased hospital utilization of the standard discharge contract as part of the GAP program is associated with decreased 1-year mortality in Medicare patient populations with AMI. Hospital efforts to promote adherence to guideline-based care tools such as the discharge contract used in GAP may result in mortality reductions for their patient populations at 1 year. PMID- 17719292 TI - Unrecognized glycometabolic disturbance as measured by hemoglobin A1c is associated with a poor outcome after acute myocardial infarction. AB - BACKGROUND: Glycated hemoglobin A1c (HbA1c) is a measure of the average blood glucose levels over 2 months and is minimally affected by acute hyperglycemia often observed in myocardial infarction (MI). In a large population of high-risk patients with MI, we examined the prognostic impact of HbA1c in patients with and without a history of diabetes. METHODS: In the OPTIMAAL trial, patients with MI complicated with heart failure were randomized to losartan or captopril. Of the 2841 patients who had HbA1c measured at randomization, 495 (17%) reported a history of diabetes. The remaining patients without diabetes history were stratified into 3 categories according to HbA1c level: HbA1c, <4.9% (n = 1642); HbA1c, 4.9% to 5.1% (n = 432); and HbA1c, >5.1% (n = 272). Mean follow-up time was 2.5 years. RESULTS: Mortality rate during follow-up was 18% in patients with a history of diabetes. Increasing HbA1c levels were associated with higher mortality rate among patients without diabetes history (13% in patients with HbA1c <4.9%, 17% in patients with HbA1c 4.9%-5.1%, 22% in patients with HbA1c >5.1%). Among patients with no prior history of diabetes, a 1% absolute increase in HbA1c level at baseline resulted in a 24% increase in mortality, whereas the level of HbA1c had no impact on mortality among the patients with well-known diabetes (multivariate analyses). CONCLUSIONS: In this high-risk MI population, HbA1c level was a potent predictor of mortality in patients without previously known diabetes. PMID- 17719293 TI - Advance directives in the cardiac care unit. AB - BACKGROUND: Despite effective therapies, mortality for many cardiovascular diseases remains higher than for many cancers and is difficult to predict. Guidelines recommend discussing advance directives (AD), including living wills and durable powers of attorney, with heart failure patients. The Patient Self Determination Act mandates such discussions with all hospitalized patients. Little data are available on AD prevalence in patients with serious cardiac disease. METHODS: Patients admitted to a cardiac care unit (CCU) were surveyed regarding demographics, medical history, prevalence of AD, and interest in obtaining more information about AD. Histories of life-threatening cardiac diagnoses were tabulated. Prevalence of AD and interest in obtaining more information about AD were obtained via chart review from patients on an oncology (ONC) floor at the same hospital. RESULTS: One hundred twelve CCU (average age 58 +/- 16 years, 47 women) and 105 ONC (average age 58 +/- 14 years, 32 women) patients were enrolled. Prevalence of AD was not different between CCU and ONC patients (26% vs 31%, P = .37). Among CCU patients with prior hospitalizations but no AD, 21 of 64 did not recall being asked about AD. Cardiac care unit patients with heart failure and pulmonary hypertension were more likely to report being asked about AD in the past (39 of 54, P = .03 and 7 of 9, P = .008, respectively), but only heart failure patients were more likely to want more information about AD (P = .005). Of patients without AD, 83% from CCU and 18% from ONC wanted more information on AD (P < .001). CONCLUSIONS: Prevalence of AD in the CCU was low, and many patients did not recall prior AD discussions. The CCU patients without AD were more likely to want information about AD than the ONC patients. A renewed emphasis on AD discussions with cardiovascular patients is needed and would be welcomed. Advance directives should be emphasized in cardiovascular training programs. PMID- 17719294 TI - Impact of diagnosis and sex on long-term prognosis in acute coronary syndromes. AB - BACKGROUND: There is limited information on long-term outcome in patients surviving the acute phase of an acute coronary syndrome (ACS). As yet, the effects of the type of syndrome and sex on mortality and morbidity in the long run have not been well described. METHODS: We studied 1618 patients <80 years old with ACS and alive 30 days after hospitalization in a coronary care unit. The patients were followed for 5 years. They were divided into 4 groups according to the type of ACS (ST-segment elevation myocardial infarction [STEMI], non-STEMI, unstable angina pectoris high risk, and unstable angina pectoris low risk). RESULTS: There was no significant sex difference in unadjusted 5-year mortality (P = .20). After adjustment for age, the hazard ratio with the corresponding 95% CI for a higher late 5-year mortality in women in relation to men was 0.89 (0.70 1.13, P = .34). Women were hospitalized for heart failure significantly more frequently during follow-up, a significance that disappeared after adjustment for age. Non-STEMI was associated with a significantly higher long-term mortality than STEMI, before but not after adjustment for covariates (hazard ratio [95% CI] 1.02 [0.75-1.37], P = .92). Of these, age, ST depression on admission, and early revascularization with percutaneous coronary intervention appeared to be of particular importance. Non-STEMI had a significantly higher rate of acute/subacute revascularization during follow-up, even after adjustment for age. CONCLUSIONS: Before, but not after, adjustment for covariates, a diagnosis of non STEMI was associated with a poorer prognosis than other types of ACS. Small sex differences in long-term outcome in survivors of ACS were found. PMID- 17719295 TI - Inpatient and follow-up cardiology care and mortality for acute coronary syndrome patients in the Veterans Health Administration. AB - BACKGROUND: The impact of inpatient and follow-up cardiology care on patient outcomes after acute coronary syndrome (ACS) hospital discharge is unknown. METHODS: This was a retrospective cohort study of all patients with ACS discharged from Veterans Health Administration facilities from 2003 to 2004. Patients were stratified into 2 categories of cardiology care: (1) inpatient and follow-up cardiology care within 60 days after discharge and (2) other levels of cardiology care (inpatient only, outpatient only, and neither inpatient nor outpatient). Multivariable regression assessed the association between inpatient and follow-up cardiology care with all-cause mortality, adjusting for demographics, comorbidities, hospital presentation and treatment variables, and clustering by site. RESULTS: Of 4933 patients with ACS, the majority (71.6%) had inpatient and follow-up cardiology care. Patients with inpatient and follow-up cardiology care were more likely to have prior coronary disease and diabetes and to present with myocardial infarction (vs unstable angina). All-cause mortality was lower for patients with inpatient and follow-up cardiology care (18.8% vs 22.1%, P = .009). In multivariable analysis, patients with inpatient and follow up cardiology care remained at lower mortality risk (hazard ratio 0.73, 95% CI 0.62-0.87) compared with patients with other levels of cardiology care. The findings were consistent when cardiology follow-up was defined as 30 or 90 days after hospital discharge. CONCLUSIONS: Patients with inpatient and follow-up cardiology care have lower mortality risk after ACS. Future studies should identify mediators of this potential benefit and determine if interventions enhancing continuity of care in general, and continuity of subspecialty care in particular, after ACS will improve patient outcomes. PMID- 17719296 TI - Effects of recombinant human erythropoietin on antiplatelet action of aspirin and clopidogrel in healthy subjects: results of a double-blind, placebo-controlled randomized trial. AB - BACKGROUND: Recombinant human erythropoietin (rHuEpo) reduces myocardial injury in experimental ischemia and has been proposed as a cardioprotective agent for potential use in acute coronary syndromes. Its safety profile in clinical acute ischemic settings is uncertain because rHuEpo has been reported to increase platelet reactivity and the risk of thromboembolism in some disease populations. Whether prothrombotic effects of rHuEpo mitigate the effects of antiplatelet agents used in acute coronary syndrome patients is unknown. METHODS: Recombinant human erythropoietin 100, 200, 400 U/kg, or placebo was given intravenously once daily for 3 consecutive days in a double-blind randomized trial in 96 healthy subjects. A single oral dose of aspirin 325 mg or clopidogrel 300 mg was given immediately after the last dose of study drug. Bleeding time and in vitro high shear stress platelet function assays (PFA)-100 were determined before; 5 hours; and 1, 5, and 7 days after aspirin or clopidogrel. RESULTS: Recombinant human erythropoietin at doses of 100 and 200 U/kg did not alter bleeding time or PFA 100 closure times at any time point when compared with placebo. Recombinant human erythropoietin at a dose of 400 U/kg significantly blunted the post-aspirin increase in bleeding time when compared with placebo (P = .03) but did not alter post-clopidogrel bleeding times nor PFA closure times. The 400-U/kg dose did not change hematocrit but did significantly increase the platelet count at 5 days after study drug administration when compared with placebo (P = .014). CONCLUSION: Short-term rHuEpo at doses up to 200 U/kg did not mitigate the effects of administration of aspirin or clopidogrel on either in vivo or in vitro measures of platelet function in healthy subjects. The 400-U/kg dose attenuated the effects of aspirin on bleeding time and increased the platelet count. Studies of the effects of rHuEpo on platelet function in patients with coronary artery disease are warranted to further characterize dose/safety profile. PMID- 17719297 TI - Association between C-reactive protein level and peripheral arterial disease among US adults without cardiovascular disease, diabetes, or hypertension. AB - BACKGROUND: Inflammatory processes are implicated in the development and progression of atherosclerotic cardiovascular disease (CVD). C-reactive protein (CRP), a specific marker of inflammation, has been found to be related to CVD and subclinical atherosclerosis, including peripheral arterial disease (PAD). However, it is not entirely clear whether CRP levels are related to subclinical CVD independent of traditional risk factors, including diabetes and hypertension. We examined the association between CRP levels and PAD among US adults free of CVD, diabetes, and hypertension. METHODS: Cross-sectional study was performed among 1611 National Health and Nutrition Examination Survey 1999-2002 participants aged > or = 40 years and without CVD, diabetes, or hypertension. Main outcome of interest was PAD defined as ankle-brachial index < 0.9. RESULTS: Higher CRP levels were positively associated with PAD, independent of smoking, waist circumference, body mass index, blood pressure, glycosylated hemoglobin, serum total cholesterol, and other confounders. Multivariable odds ratio (95% CI) comparing quartile 4 of CRP (> 0.54 mg/dL) to quartile 1 (< 0.09 mg/dL) was 6.38 (1.77-22.96); P trend = .005. This association persisted in separate analysis in men and women. Furthermore, the results were consistent in subgroup analyses by categories of age, education, smoking, and body mass index. In nonparametric models, the positive association between CRP and PAD seemed to be present across the full range of CRP without any apparent threshold. CONCLUSIONS: Higher CRP levels are associated with PAD among US adults free of CVD, diabetes, and hypertension. These results suggest that inflammatory mechanisms related to atherosclerosis may be operative even among clinically healthy adults. PMID- 17719298 TI - Differences in cardiac stress testing by sex and race among Medicare beneficiaries. AB - BACKGROUND: Although there is a wide literature demonstrating sex and race differences in the receipt of invasive cardiac tests and treatments, much less is known about the influence of such characteristics on receipt of a stress test, the first event in the diagnostic/treatment cascade for many patients. We explored the influence of patient characteristics on receipt of a stress test, with special attention to sex and race. METHODS: We performed a nested case control study of Medicare beneficiaries who were aged 66 years and older during 1999-2001 and were free of cardiac diagnoses and procedures for at least 1 year. Cases were recipients of a stress test. RESULTS: Cases were younger, less likely to be female or black, but more likely to live in high-income, highly educated, and urban areas than controls. Nonblack men were more likely to receive a stress test than women and black men, controlling for age, area characteristics, and clinical characteristics (odds ratio for nonblack men compared with black women 1.71). These results were not explained by physician visit frequency. CONCLUSIONS: Efforts at minimizing disparities in cardiac care must attend to what is, for many patients, the entry into the cardiac care system: the stress test. Our findings suggest that simple "access," as measured by physician visit frequency, is not a rate-limiting factor. PMID- 17719299 TI - Left ventricular opacification for the diagnosis of coronary artery disease with stress echocardiography: an angiographic study of incremental benefit and cost effectiveness. AB - BACKGROUND: Left ventricular opacification (LVO) improves image quality at stress echocardiography (SE). We examined whether routine use of LVO adds incremental benefit and is cost-effective for diagnosis of coronary artery disease (CAD). METHODS: Contrast pharmacologic and/or exercise SE was performed in 135 patients (81 men; 56 +/- 10 years) undergoing coronary angiography. Observers sequentially interpreted first standard, then LVO images; a positive SE was defined by resting or inducible wall motion abnormality in > or = 2 segments. Coronary artery disease (75 patients, 119 territories) was defined as > 50% stenosis. Three cost effectiveness models were studied, and a sensitivity analysis was performed. RESULTS: Left ventricular opacification increased the sensitivity of SE (80%-91%; P = .03), including single-vessel CAD (65%-87%; P = .04), with no significant change in specificity (72%-77%; P = NS). Left ventricular opacification was of benefit to 14% of patients, unrelated to resting image quality. Use of LVO in all patients added 59% to the cost of the procedure (P < .001), at a cost of $1069 per additional correct diagnosis. In a cost-effectiveness model based on cardiac outcomes after SE, LVO resulted in an increase in total cost of $1069. A 3.7% improvement in sensitivity resulted in a negative cost to identify CAD, but even 15% to 20% improvements in specificity failed to balance the cost of contrast for exclusion of CAD. CONCLUSIONS: Left ventricular opacification adds significant incremental diagnostic benefit to standard SE, especially single-vessel CAD. Despite improved sensitivity, the use of contrast in all patients was not cost effective when analyzed with a model based on previously published patient outcomes. PMID- 17719300 TI - Evaluation of coronary artery bypass grafts and native coronary arteries using 64 slice multidetector computed tomography. AB - BACKGROUND: The conventional use of 16-slice multidetector computed tomography (MDCT) remains somewhat limited for evaluating stenoses in vein graft distal anastomotic sites and in coronary arteries. We investigated the diagnostic accuracy of 64-slice MDCT for assessment of both grafts and coronary arteries in patients with coronary artery bypass grafts. METHOD: The study group included 54 consecutive patients. One patient had to be excluded from the study because of arrhythmia. The remaining 53 patients with coronary artery bypass grafts underwent both 64-slice MDCT angiography and invasive coronary angiography. The MDCTs were analyzed for presence of significant stenosis (>50%) or occlusion in grafts and coronary arteries. The results were compared with those of invasive coronary angiography. RESULTS: Overall, 138 of 146 (94.5%) grafts including distal anastomoses were evaluable with MDCT. Evaluability of arterial grafts, venous grafts, distal runoff arteries, and nongrafted arteries was 90.3%, 98.6%, 84.0%, and 97.3%, respectively. After censoring nonevaluable grafts or arteries and considering them to be positive, the sensitivity to detect significant stenosis or occlusion in arterial grafts was 100% and specificity was 91.4%. In venous graft, sensitivity was 100% and specificity was 98.1%. In distal runoff arteries, sensitivity to detect significant stenoses was 83.3% and specificity was 80.2%. In nongrafted arteries, sensitivity was 100% and specificity was 87.5%. CONCLUSIONS: Sixty-four-slice MDCT showed improved ability to assess bypass grafts and coronary arteries. However, there were still difficulties in assessment of distal runoff arteries in which relatively low diagnostic accuracy was observed that might limit clinical implementation of MDCT. PMID- 17719301 TI - Echocardiographic characteristics of professional tennis players at the Roland Garros French Open. AB - BACKGROUND: Intensive sport may induce cardiac modifications. No recent study has been performed in elite tennis players. The aim of this cross-sectional study was to analyze the cardiac characteristics in a population of professional tennis players. METHODS: During the 2004 French Open Tennis Tournament, we offered complete echocardiographic screening to all professional tennis players. The study population consisted of 160 subjects: 80 tennis players (50 men and 30 women) and age- and sex-matched control groups (n = 80). RESULTS: Indexed left ventricular mass was significantly higher in tennis players (P < .0001). Left ventricular hypertrophy was present in 18 male (36%) and 6 female (20%) tennis players versus 2 men (4%) and no woman in the control groups (P < .0001 and P = .02, respectively). All indexed right and left atrial measurements were significantly higher in tennis players (P < .003). The incidence of left and right atrial dilation was significantly higher in tennis players (P < or = .0001). Indexed right atrial area and left atrial volume were significantly higher in baseline players as compared with offensive players and to control groups (P < .0001), whereas there was no significant difference in left ventricular mass according to the style of play (P > .75). No significant between group difference was observed in Doppler data. CONCLUSIONS: In the present study, professional tennis players presented significant cardiac differences, as compared to a control group, with moderate left ventricular hypertrophy, bilateral atrial dilation, and normal systolic and diastolic functions. Atrial dilation is related to the style of play (baseline or offensive) and should be considered as physiological in tennis players. PMID- 17719302 TI - Mobile cardiac catheterization laboratories increase use of cardiac care in women and African Americans. AB - BACKGROUND: Women and minorities traditionally have shown less use of diagnostic cardiac catheterization. We sought to determine whether mobile cardiac catheterization laboratories may increase the use of catheterization among women and minorities by bringing the technology to remote communities. METHODS: We collected data on consecutive patients undergoing cardiac catheterization at mobile laboratories located at 15 community hospitals in North Carolina and Virginia from 1994 to 2005. These data were compared with those from similar consecutive outpatients at the Duke University Medical Center (Durham, NC) cardiac catheterization laboratory over the same period. Logistic regression modeling techniques were used to determine which patient factors were associated with the decision to use a particular facility. RESULTS: Women comprised 48% of the patients undergoing cardiac catheterization via mobile laboratory versus 42% of those patients receiving outpatient catheterization at the medical center laboratory (P < .001). All racial minorities combined (African American, Hispanic, Native American, Asian, and other) made up 27% of the mobile laboratory population undergoing catheterization versus 21% of the medical center outpatients who underwent the procedure (P < .001). Most minorities were African American. The most important predictor of patients receiving catheterization via a mobile laboratory rather than at the medical center catheterization laboratory was distance to the nearest mobile facility. Within a home-to-mobile laboratory range of approximately 35 miles, the odds of being treated at a mobile laboratory increased greatly the closer the patient lived to the facility. CONCLUSIONS: The strongest predictor of mobile laboratory use was the patient's proximity to the mobile facility. When compared with a traditional tertiary referral outpatient hospital setting, a greater percentage of women and African Americans received cardiac catheterization at mobile laboratories. The availability of mobile laboratories may increase the use of cardiac procedures among women and African Americans. PMID- 17719303 TI - Sodium bicarbonate, N-acetylcysteine, and saline for prevention of radiocontrast induced nephropathy. A comparison of 3 regimens for protecting contrast-induced nephropathy in patients undergoing coronary procedures. A single-center prospective controlled trial. AB - BACKGROUND: Several protective therapies have been developed to prevent contrast induced nephropathy (CIN). We aimed to investigate the efficacy of sodium bicarbonate by comparing 2 other regimens, including combination of N acetylcysteine (NAC) plus sodium chloride and sodium chloride alone, to prevent CIN in patients undergoing cardiovascular procedures. METHODS: We prospectively enrolled 264 patients who were scheduled for cardiovascular procedures and had a baseline creatinine level >1.2 mg/dL. The patients were assigned 1 of 3 prophylactic regimens: infusion of sodium bicarbonate, sodium chloride, sodium chloride plus oral NAC (600 mg bid). Contrast-induced nephropathy was defined as an increase in serum creatinine level >25% or 0.5 mg/dL after 48 hours. RESULTS: There were no significant differences among groups regarding baseline demographic properties and nephropathy risk factors. The change in creatinine clearance was significantly better in the sodium bicarbonate group than other 2 groups (P = .007). The incidence of CIN was significantly lower in the sodium bicarbonate group (4.5%) compared with sodium chloride alone (13.6%, P = .036) and tended to be lower than in the combination group (12.5%, P = .059). After adjusting the Mehran nephropathy risk score, the risk of CIN significantly reduced with sodium bicarbonate compared with sodium chloride alone (adjusted risk ratio 0.29, P = .043). CONCLUSIONS: Hydration with sodium bicarbonate provides better protection against CIN than the sodium chloride infusion does alone. Combination therapy of NAC plus sodium chloride did not offer additional benefit over hydration with sodium chloride alone. PMID- 17719304 TI - A comparison of mortality, myocardial infarction, and repeated revascularization for sirolimus-eluting and paclitaxel-eluting coronary stents. AB - BACKGROUND: Drug-eluting stents are now used in most percutaneous coronary interventions. There are only 2 approved devices: sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). Only a few population-based studies have compared their patient outcomes. METHODS: All New York State patients undergoing SES or PES in nonfederal hospitals in the state between April 1 and December 31, 2004, except those with a previous revascularization, left main coronary artery disease, or a recent myocardial infarction (MI) or shock (4867 patients with PES and 6914 with SES) were followed up through the end of 2005. We compared SES and PES with respect to inhospital and 18-month mortality, 18-month mortality/MI, and subsequent target vessel and target lesion revascularization (TVR and TLR) after adjusting for differences in patient risk factors. RESULTS: By 18 months after receiving a PES, 4.0% of the patients died compared with 4.1% for SES patients, 5.9% of PES patients experienced mortality/MI compared with 6.3% of SES patients, 6.8% of the PES patients had a subsequent TVR within 18 months compared with 7.8% for SES patients, and 4.5% of the PES patients had a subsequent TLR within 18 months compared with 5.3% for SES patients. The respective adjusted hazards ratios (PES/SES) for these adverse outcomes were 1.02 (95% CI 0.82-1.26, P = .86), 0.94 (95% CI 0.78-1.13, P = .52), 0.89 (95% CI 0.75-1.06, P = .20), and 0.86 (95% CI 0.70-1.05, P = .14). CONCLUSIONS: Patients receiving PES and SES do not have significantly different 18-month mortality, mortality/MI, subsequent TVR, or subsequent TLR rates. PMID- 17719305 TI - Intensity of lipid-lowering therapy and low-density lipoprotein cholesterol goal attainment among the elderly before and after the 2004 National Cholesterol Education Program Adult Treatment Panel III update. AB - BACKGROUND: In 2004, the Coordinating Committee of the National Cholesterol Education Program issued an update to the Adult Treatment Panel III guidelines on cholesterol management (the Update). Our objectives were to compare the proportion of elderly patients receiving intensive or minimal-guideline lipid lowering therapy and the proportions meeting low-density lipoprotein cholesterol (LDL-C) goals before and after the update. METHODS: We used dispense records from Kaiser Permanente Northwest (Portland, OR) to identify elderly patients who received statin therapy in 2003 (n = 14425) and 2005 (n = 19422) and laboratory records to assess LDL-C goal attainment. RESULTS: Among new statin initiators, 85.4% of very-high-risk patients received minimal-guideline therapy in 2005, compared with 65.3% (P < .0001) in 2003. Of all new initiators, <1% received very aggressive therapy in either year (0.4% vs 0.3%, P = .315). Overall, 77.7% and 59.0% of ongoing users in 2005 and 2003, respectively, received minimal-guideline therapy (P < .0001). Low-density lipoprotein cholesterol goal attainment did not differ between 2003 and 2005 continuing statin users. Among very-high-risk patients who initiated statin treatment, a significantly greater proportion of patients in 2005 versus 2003 attained the optional goal of <70 mg/dL (45.5% vs 34.4% P = .014). However, there was no significant difference in the proportion attaining <100 mg/dL (77.8% vs 81.8%, P = .281). CONCLUSION: After the Update, more elderly patients were receiving intensive or minimal-guideline statin therapy. Low-density lipoprotein cholesterol goal attainment was isolated and appeared to occur by shifting already well-controlled patients to lower LDL-C levels. Although these findings may translate into less overall coronary heart disease risk, more aggressive lipid-lowering therapy would likely further reduce risk. PMID- 17719306 TI - Land versus water exercise in patients with coronary artery disease: effects on body composition, blood lipids, and physical fitness. AB - BACKGROUND: We examined the effects of combined resistance and aerobic training on land versus combined resistance and aerobic training in water in patients with coronary artery disease. METHODS: Thirty-four patients were randomly assigned to land exercise (LE, n = 12), water exercise (WE, n = 12), and control (n = 10) groups. The LE group trained 4 times per week, twice with aerobic exercise and twice with resistance training. The WE program included aquatic aerobic activities 2 times per week and resistance exercise at the same frequency carried out in water. The duration of the training programs was 4 months. Body composition measurements, blood lipids, exercise stress testing, and muscular strength were obtained at the beginning and at the end of the training period. RESULTS: After 4 months of training, analysis of covariance revealed that body weight and sum of skinfolds were lower for WE and LE groups than for the control group. Patients who trained in water improved exercise time (+11.7% vs +8.1%) and maximum strength (+12.8% vs +12.9%) in a similar manner compared to the patients who trained on land. Total cholesterol (WE -4.4%, LE -3.3%) and triglycerides (WE -10.2%, LE -11.8%) decreased significantly for both exercise groups but not for the control group. CONCLUSIONS: Exercise programs that combine resistance and aerobic exercise performed either on land or in water can both improve exercise tolerance and muscular strength in patients with coronary artery disease. Furthermore, both programs induce similar favorable adaptations on total cholesterol, triglycerides, and body composition. PMID- 17719307 TI - Connexin37 (GJA4) genotype predicts survival after an acute coronary syndrome. AB - BACKGROUND: GJA4 1019 C > T, MMP3 -1171delA, and SERPINE1 -668delG genotypes have been associated with the risk of incident myocardial infarction. We tested the hypothesis that these genotypes would predict long-term mortality after an acute coronary syndrome (ACS). METHODS: We assembled a prospective cohort study on 726 patients with ACS admitted between March 2000 and October 2001. Kaplan-Meier estimates and Cox proportional hazards models of 3-year mortality adjusted for age, race, ACS type, prior heart failure, diabetes, and revascularization were used to compare groups. RESULTS: The GJA4 1019 C > T genotype was significantly related to mortality over 3 years (8.3% vs 14%, for the C/C vs T allele carriers; P = .02), with an adjusted hazard ratio of 1.7 (95% confidence interval 1.05-2.8, P = .03). This finding was consistent in both men and women (hazard ratio = 1.9 and 1.7, respectively) with no significant sex interaction (P = .8). The MMP3 1171delA and SERPINE1 -668delG genotypes were not significantly related to mortality in the overall population (all P > .4). CONCLUSIONS: GJA4 1019 C > T genotype predicted risk of death after an ACS, whereas the MMP3 and SERPINE1 genotypes did not. The GJA4 1019 C > T polymorphism may warrant integration into comprehensive risk stratification algorithms for patients with ACS. PMID- 17719308 TI - Prevalence and prognosis of left ventricular systolic dysfunction in asymptomatic diabetic patients without known coronary artery disease referred for stress single-photon emission computed tomography and assessment of left ventricular function. AB - BACKGROUND: The prevalence and prognosis of reduced left ventricular ejection fraction (LVEF) in asymptomatic diabetic patients without known coronary artery disease (CAD) are not known. METHODS: We examined 1046 asymptomatic diabetic patients (age 60 +/- 13 years, 69% male) without known CAD referred to a tertiary referral center for stress single-photon emission computed tomography (SPECT) and assessment of LVEF. Patients were stratified according to the presence of normal LVEF (> or = 50%), mildly reduced LVEF (35%-49%), or moderately/severely reduced LVEF (< 35%). Single-photon emission computed tomographic images were classified as low, intermediate, or high risk based on the summed stress score (normal = 56). The mean follow-up was 5.3 +/- 3.3 years. RESULTS: The prevalence of reduced LVEF was 16.7% (n = 175, mean LVEF 40.0% +/- 7.7%). This group was older (63 +/- 11 vs 59 +/- 14 years, P = .005), had more peripheral arterial disease (45% vs 29%, P < .001), and had a higher prevalence of electrocardiographic Q waves (21% vs 9%, P < .001) than the group without reduced LVEF. Mean summed stress (44.8 +/ 9.8 vs 51.7 +/- 6.3, P < .001), summed reversibility (4.7 +/- 5.0 vs 2.9 +/- 4.5, P < .001), and summed rest scores (49.4 +/- 7.2 vs 54.6 +/- 3.1, P < .001) were significantly more abnormal in the reduced LVEF group. High-risk summed stress score was significantly more common in the reduced LVEF group (46% vs 16%, P < .001). Survival was significantly lower in patients with any reduction in LVEF compared with those without reduced LVEF (10-year survival, 29% vs 57%, P < .0001). By multivariate analysis, reduced LVEF was independently associated with increased mortality (adjusted chi2 = 6.26, P = .01). CONCLUSIONS: In this population of asymptomatic diabetic patients without known CAD referred for stress SPECT, 1 in 6 patients had reduced LVEF. Most of these patients have intermediate-/high-risk SPECT scans. The annual mortality rates of the groups with and without reduced LVEF were 7% and 4%, respectively. PMID- 17719309 TI - Sex differences in basal hemodynamics and left ventricular function in humans with and without heart failure. AB - BACKGROUND: Women with systolic heart failure (HF) demonstrate better survival than men. Whether sex differences occur in hemodynamics or measures of left ventricular (LV) function is not well understood. METHODS: We retrospectively analyzed a cohort who underwent evaluation by right heart catheterization +/- micromanometer-tipped catheterization of the LV. Two groups, defined at the time of catheterization, were studied: normal LV (NLV) function or HF (LV ejection fraction <35%, New York Heart Association II-III symptoms). For each female, we identified 2 male controls matched for age and LV ejection fraction in the HF group. RESULTS: In the NLV group, we matched 73 men (56 +/- 10 years) to 39 women (56 +/- 10 years). In the HF group, we matched 71 men (57 +/- 10 years) to 36 women (57 +/- 10 years). In the NLV group, women had higher heart rate and lower right atrial pressure, mean pulmonary artery pressure, and pulmonary capillary wedge pressure. Left ventricular peak systolic pressure was higher, and LV end diastolic pressure was lower in women. In the HF group, no sex differences were observed in any hemodynamic measurement. In both groups, no sex differences were observed in isovolumic contractility or relaxation. CONCLUSIONS: Sex differences in hemodynamics are observed in patients with NLV function but not with HF. The intrinsic or extrinsic factors responsible for sex differences observed in patients with NLV function may be eclipsed by the HF disease state or its treatment. PMID- 17719310 TI - Association between toll-like receptor 8 expression and adverse clinical outcomes in patients with enterovirus-associated dilated cardiomyopathy. AB - BACKGROUND: In recent reports, human toll-like receptor (TLR) 8 mediates the antiviral response by recognizing single-stranded RNA. The inflammatory response against enteroviral (EV) RNA replication may play an important role in dilated cardiomyopathy (DCM). The purpose of this study was to determine whether TLR8 was expressed with EV replication in patients with enterovirus-associated DCM. METHODS: Reverse transcriptase-polymerase chain reaction analysis was performed to screen the detection of myocardial EV RNA in 198 consecutive patients with DCM. Seventy-two EV RNA-positive patients with DCM and 20 control samples constituted the study population of the present study. Levels of TLR8 and myeloid differentiation factor (MyD) 88 adaptor protein mRNA and EV RNA (plus- and minus strand RNAs) were measured by real-time RT-PCR. Immunohistochemistry was performed to identify the cellular source of these molecules. RESULTS: Toll-like receptor 8 and MyD88 mRNA levels were higher in patients with DCM than in controls (P < .001). Immunostainings of TLR8, MyD88, and EV protein showed localization of these proteins in cardiac myocytes in patients with DCM. After a mean follow-up of 426 days, clinical outcomes (development of heart failure n = 11, cardiac death n = 3) were associated with increased levels of TLR8 and MyD88 (P < .05). Multivariate analysis showed that TLR8 (relative risk 3.2, 95% CI 1.6 6.2) was a strong predictor of heart failure and cardiac death after adjustment for baseline characteristics. CONCLUSION: Toll-like receptor 8 and MyD88 expressions may be involved in the immune response to EV replication in enterovirus-associated DCM. In addition, TLR8 may provide important prognostic information in patients with enterovirus-associated DCM. PMID- 17719311 TI - The effects of beta-blockers in patients with stable chronic heart failure. Predictors of left ventricular ejection fraction improvement and impact on prognosis. AB - BACKGROUND: Previous studies, with limited number of patients, have tried to determine the predictors of left ventricular ejection fraction (LVEF) improvement after beta-blockade. No study has demonstrated that LVEF improvement was an independent predictor of cardiac survival. METHODS: The aims of the study were to determine in a large group of patients with stable chronic heart failure associated with reduced LVEF the predictors of LVEF improvement (difference in LVEF [deltaLVEF], ie, the value after beta-blockade minus the value before beta blockade) after beta-blockade and to analyze prognostic impact of deltaLVEF. Three hundred fourteen consecutive patients underwent an echocardiogram, a radionuclide angiogram, and a maximum cardiopulmonary exercise test before and 3 months after maximal tolerated doses of beta-blockers have been reached. RESULTS: After beta-blockade, LVEF improved from 30% +/- 11% to 40% +/- 13%. In the whole population, independent predictors of deltaLVEF were nonischemic etiology, baseline LVEF (negative correlation), and baseline heart rate (positive correlation). In ischemic patients, independent predictors of deltaLVEF were absence of history of myocardial infarction, baseline heart rate, and baseline LVEF; whereas in nonischemic patients, independent predictors were baseline LVEF and baseline QRS width (negative correlation). After 1082 days of follow-up, there were 53 cardiovascular deaths and 2 urgent transplantations. Left ventricular ejection fraction improvement (defined as an absolute increase in LVEF > 5%) was an independent predictor of cardiac survival. Patients who had an LVEF < or = 45% after beta-blockade with a deltaLVEF < or = 5% represented a high risk subgroup. CONCLUSIONS: In patients with chronic heart failure, predictors of LVEF improvement after beta-blockade were different according to etiology. Left ventricular ejection fraction improvement was an independent predictor of cardiac survival. PMID- 17719312 TI - Perindopril preventive treatment on mortality in Duchenne muscular dystrophy: 10 years' follow-up. AB - BACKGROUND: Duchenne muscular dystrophy (DMD), an X-linked disorder due to lack of dystrophin, is associated with muscle weakness and myocardial dysfunction. Although preliminary data support the efficacy of angiotensin-converting enzyme inhibitors on left ventricular (LV) function, our aim was to examine the long term impact of a preventive treatment with perindopril on mortality in children with DMD. METHODS: Patients with DMD between the ages of 9.5 and 13 years presenting with normal LV ejection fraction were included in this prospective study. They were randomly assigned for 3 years to perindopril, 2 to 4 mg (group 1), or placebo (group 2) in a double-blind protocol, followed by open-label treatment with perindopril for up to 10 years. Survival rate at 10 years in each group is reported. RESULTS: There were 28 patients assigned to group 1 and 29 to group 2. Baseline characteristics were similar in both groups. At the end of the 10 years' follow-up period, survival status was available for all included patients: 26 (92.9%) of 28 patients in group 1 were alive at 10 years versus 19 (65.5%) of 29 in group 2 (P = .02). Kaplan-Meier cumulative survival was significantly lower in group 2 than in group 1 (P = .013). CONCLUSION: Early initiation of treatment with perindopril is associated with a lower mortality in patients with DMD with normal LV ejection fraction at study entry. PMID- 17719313 TI - Beneficial effects of trimetazidine treatment on exercise tolerance and B-type natriuretic peptide and troponin T plasma levels in patients with stable ischemic cardiomyopathy. AB - BACKGROUND: In patients with ischemic cardiomyopathy, mortality rate and quality of life are unsatisfactory. We investigated the effects of the metabolic agent trimetazidine (TMZ) on exercise tolerance and prognostic markers B-type natriuretic peptide (BNP) and cardiac troponin T (cTnT) plasma levels. METHODS: Fifty patients with ischemic cardiomyopathy were randomized either to receive TMZ (20 mg, TID) in addition to their conventional treatment (TMZ group, n = 25) or to continue their usual drug therapy (control group, n = 25) for 6 months. Patients were evaluated at baseline, at 1 month, and at 6 months (echocardiography and 6-minute walking test). At enrollment and at the end of follow-up, blood testing was performed for determination of BNP and cTnT plasma levels. RESULTS: After 6 months, no significant New York Heart Association class changes occurred in all patients (P = NS). In the TMZ group, a significant increase of exercise tolerance (P < .01) was detected, whereas left ventricular ejection fraction was unchanged (28% +/- 4%, 29% +/- 5%, and 32% +/- 5% at baseline, at 1 month, and at 6 months, respectively; P = NS). In the TMZ group, BNP was significantly reduced (6 months, 135 +/- 22 vs 252 +/- 44 pg/mL; P < .001), whereas it was significantly increased in controls (6 months, 288 +/- 46 vs 239 +/- 59 pg/mL; P < .02); cTnT significantly (P < .001) reduced during TMZ treatment, whereas it was unchanged in the control group. CONCLUSIONS: Six-month TMZ treatment improves exercise tolerance and reduces plasma levels of BNP and cTnT in patients with compensated ischemic cardiomyopathy. PMID- 17719314 TI - Safety and efficacy of Atorvastatin-induced very low-density lipoprotein cholesterol levels in Patients with coronary heart disease (a post hoc analysis of the treating to new targets [TNT] study). AB - High-dose statin therapy has been demonstrated to provide incremental benefit when low-density lipoprotein (LDL) cholesterol concentrations are lowered well below recommended target levels. This secondary analysis of the Treating to New Targets (TNT) study was conducted to investigate whether the attainment of very low LDL cholesterol levels was associated with a further reduction in major cardiovascular events compared with higher LDL cholesterol concentrations and whether any incremental benefit was achieved without additional safety risk. Patients with coronary heart disease and LDL cholesterol levels <130 mg/dl (3.4 mmol/L) were randomized to therapy with atorvastatin 10 mg/day (n = 5,006) or 80 mg/day (n = 4,995). The primary end point was the occurrence of a first major cardiovascular event. Clinical outcomes and safety data were compared across on treatment LDL cholesterol quintiles. There was a highly significant reduction in the rate of major cardiovascular events with descending achieved levels of on treatment LDL cholesterol (p <0.0001 for trend across LDL cholesterol). Analysis of individual components of the primary end point demonstrated similar results. Death from any cause and from noncardiovascular causes was lowest in patients with the lowest on-treatment LDL cholesterol levels. Cardiovascular deaths were also reduced with lower levels of on-treatment LDL cholesterol. There were no clinically important differences in adverse event rates across quintiles. Specifically, no increase in muscle complaints, suicide, hemorrhagic stroke, or cancer deaths was observed at the lowest LDL cholesterol levels. In conclusion, the present analysis adds support to the concept that for patients with established atherosclerotic cardiovascular disease, a further risk reduction without sacrifice of safety can be achieved by reducing LDL cholesterol to very low levels. PMID- 17719315 TI - Relation of C-reactive protein and new-onset atrial fibrillation in patients with acute myocardial infarction. AB - Recent studies have implicated systemic inflammation in the genesis and maintenance of atrial fibrillation (AF). A robust inflammatory response is an integral component of the response to tissue injury during acute myocardial infarction (AMI). However, there is no information concerning the association between inflammation and AF in patients with AMI. We studied 1,209 patients admitted for AMI. C-reactive protein (CRP) was measured by a high-sensitivity assay within 12 to 24 hours after symptom onset. The relation between CRP and new onset AF occurring during the hospital course and at 1 year was analyzed using multivariable logistic regression and Cox models, respectively. New-onset AF during hospitalization occurred in 6.5%, 10.4%, and 17.1% of patients in the first, second and third CRP tertiles, respectively (p trend <0.0001). In a multivariable logistic regression, adjusting for clinical variables and ejection fraction, compared with patients in the first CRP tertile, the odds ratios for AF were 1.5 (95% confidence interval 0.9 to 2.5, p = 0.15) and 2.0 (95% confidence interval 1.2 to 3.3, p = 0.008) in patients in the second and third CRP tertiles, respectively (p for trend = 0.007). In a Cox multivariate analysis, CRP remained an independent predictor of new-onset AF at 1 year. In conclusion, in a large cohort of patients with AMI, there was a graded positive association between increased CRP and new-onset AF. Inflammation may contribute to the development of AF in the setting of AMI. PMID- 17719316 TI - Serial changes in von Willebrand factor-cleaving protease (ADAMTS13) and prognosis after acute myocardial infarction. AB - Von Willebrand factor (VWF), a cofactor in platelet adhesion and aggregation, increases hemostasis and thrombosis. Recently, a metalloprotease that cleaves VWF multimers has been identified, namely ADAMTS13. The aim of this study was to investigate the relation between serial changes in plasma VWF and ADAMTS13 and the prognosis after acute myocardial infarction (AMI). We measured serial changes of plasma VWF and ADAMTS13 antigen levels in 92 patients with AMI and 40 control subjects. VWF levels were significantly higher in patients with AMI compared with controls (p <0.01) on admission, peaked 3 days after admission, and remained high for 14 days. In contrast, on admission, ADAMTS13 levels were significantly lower in patients with AMI compared with controls (p <0.0001), with minimum antigen levels reached after 3 days, and remained lower for 14 days. The ratio of VWF/ADAMTS13 antigen levels was higher in patients with AMI compared with controls throughout the time course. Cox hazards analysis revealed that the early increase of VWF and VWF/ADAMTS13 ratio levels and the early decrease of ADAMTS13 levels were significant predictors of future thrombotic events during the 1-year follow-up period. Kaplan-Meier analysis demonstrated that patients with major decreases of ADAMTS13 levels and high increases of VWF/ADAMTS13 levels had significantly greater probabilities for development of thrombotic events (p = 0.0104 and 0.0209, respectively). In conclusion, these findings suggest that monitoring the changes of VWF and ADAMTS13 antigen levels in the early phase might be valuable for predicting and preventing thrombosis during 1-year follow up in patients with AMI. PMID- 17719317 TI - Usefulness of detectable levels of troponin, below the 99th percentile of the normal range, as a clue to the presence of underlying coronary artery disease. AB - The aim of the study was to evaluate whether markers of myocardial injury and ischemia are helpful in detecting coronary artery disease (CAD) in patients with stable angina. Venous blood was obtained before and after a bicycle exercise test in 47 outpatients with suspected CAD for measurement of cardiac troponin I (cTnI), heart-type fatty acid binding protein, and glycogen phosphorylase BB. Patients with a coronary artery stenosis >/=70% in diameter (n = 33) were compared with patients with coronary narrowing <50% (controls, n = 14). None of the markers increased after bicycle exercise testing. cTnI measured before and after exercise was higher in the CAD group than in controls (p <0.001). The area under the curve for diagnosis was greater when the cTnI value was detectable than with stress testing alone. In conclusion, baseline cTnI was of value in detecting CAD and also during follow-up in predicting the need for further revascularization. PMID- 17719318 TI - Meta-analysis of published reports on the effect of statin treatment before percutaneous coronary intervention on periprocedural myonecrosis. AB - Myonecrosis, manifested by an increase in cardiac markers, may occur in up to 50% of patients undergoing elective percutaneous coronary intervention (PCI). The degree of periprocedural myonecrosis, measured by the peak creatine kinase-MB fraction, has been associated with incidence of adverse clinical outcomes. Therefore, strategies to decrease myonecrosis may translate into a decrease in mortality. We evaluated the efficacy of statin pretreatment in decreasing the incidence of myonecrosis after PCI on the basis of results of published studies. A systematic search of the PubMed database from its inception to October 2006 and from the references of identified studies was performed. Only studies with concurrent control groups were included. Information on baseline characteristics of included patients and clinical outcomes was independently extracted by 2 investigators. A random effects model was used to pool odds ratios of the incidence of periprocedural myonecrosis in statin-treated patients versus controls. A total of 9 trials was included in the analysis, 2 randomized trials (n = 604) and 7 retrospective cohort studies (n = 4,751), which assessed the impact of statin pretreatment on periprocedural myonecrosis. During this period, 196 of 2,149 patients (9%) in the statin-treated group compared with 455 of 2,602 (17.5%) in the control group (odds ratio 0.45, 95% confidence interval 0.33 to 0.62, p <0.01) developed myonecrosis. In conclusion, based on existing evidence, routine pretreatment with statins may decrease the risk of postprocedure myonecrosis. Large randomized controlled trials addressing the dose, duration, and type of statin on periprocedural myonecrosis are necessary before recommending routine use of statins to prevent myonecrosis in the elective PCI setting. PMID- 17719319 TI - Predictors of in-stent restenosis and patient outcome after percutaneous coronary intervention in patients with diabetes mellitus. AB - Diabetics have a significantly higher incidence of major adverse cardiac events (MACEs) and in-stent restenosis (ISR) than nondiabetics after percutaneous coronary intervention (PCI). Predictors of MACEs and ISR are uncertain in diabetics. In recent studies, microalbuminuria and proliferative retinopathy have been believed to relate to progressive coronary atherosclerosis. We retrospectively studied 191 consecutive patients (mean age 65 +/- 9 years) with diabetes who underwent PCI to determine predictors of ISR and MACEs (defined as cumulative incidence of myocardial infarction, revascularization, or death from cardiovascular cause), with special reference to microalbuminuria and proliferative retinopathy. Of 191 patients, 106 (56%) had a follow-up coronary angiogram at 16 +/- 2 months. Of these 106 patients, 66 (62%) developed ISR. In the multivariate model, microalbuminuria or proliferative retinopathy did not achieve significant association with ISR. Serum high-density lipoprotein cholesterol levels were significantly associated with a lower incidence of ISR (odds ratio [OR] 0.928, 95% confidence interval [CI] 0.876 to 0.983, p = 0.011) and MACEs (OR 0.96, 95% CI 0.931 to 1.000, p = 0.048). Use of drug-eluting stents also had a negative association with ISR (OR 0.171, 95% CI 0.05 to 0.585, p = 0.004). Renal insufficiency was associated with higher MACEs (OR 3.19, 95% CI 1.45 to 7.031, p = 0.0039). In conclusion, serum high-density lipoprotein cholesterol levels were inversely associated with ISR or MACEs. PMID- 17719320 TI - Comparison of usefulness of sodium bicarbonate versus sodium chloride to prevent contrast-induced nephropathy in patients undergoing an emergent coronary procedure. AB - In the case of an emergency coronary procedure where the risk of contrast-induced nephropathy is especially high, there are few reliable methods to attenuate renal injury. We examined the efficacy of sodium bicarbonate for the prevention of contrast-induced nephropathy in patients undergoing an emergency coronary procedure. We enrolled 59 patients who were scheduled to undergo an emergency coronary angiography or intervention. These patients were randomized to receive a 154-mEq/L infusion of sodium bicarbonate (n = 30) or sodium chloride (n = 29), as a bolus of 3 ml/kg/hour for 1 hour before the administration of contrast, followed by an infusion of 1 ml/kg/hour for 6 hours during and after the procedure. In the sodium bicarbonate group, serum creatinine concentration remained unchanged within 2 days of contrast administration (1.31 +/- 0.52 to 1.31 +/- 0.59 mg/dl), whereas it increased in the sodium chloride group (1.32 +/- 0.65 to 1.52 +/- 0.92 mg/dl, p = 0.01). The incidence of contrast-induced nephropathy (an increase >0.5 mg/dl or >25% in serum creatinine concentration within 2 days of contrast) was significantly lower in the sodium bicarbonate group than in the sodium chloride group (7% vs 35%, p = 0.01, risk ratio 0.19, 95% confidence interval 0.046 to 0.80). In conclusion, hydration with sodium bicarbonate is more effective than with sodium chloride for the prevention of contrast-induced nephropathy in patients undergoing an emergency coronary procedure. PMID- 17719321 TI - Usefulness of prehospital triage in patients with cardiogenic shock complicating ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. AB - We investigated the impact of ambulance-based prehospital triage on treatment delay and all-cause mortality (in hospital and long term) in patients with ST elevation myocardial infarction (STEMI) complicated by cardiogenic shock referred for primary percutaneous coronary intervention in a prospectively collected registry. During the study period (January 2003 to December 2005), a total of 121 patients was referred for primary percutaneous coronary intervention at our intervention laboratory through 2 main triage groups: (1) after prehospital, ambulance-telemedicine-based triage (42 patients) and (2) by more conventional routes (79 patients) represented by the institutional S. Orsola-Malpighi hospital emergency department triage (44 patients) and spoke hospital triage (35 patients). Total ischemic time was shorter in the prehospital triage (142 minutes, range 106 to 187, vs 212 minutes, range 150 to 366, p = 0.003). Patients with prehospital triage showed a lower rate (29% vs 54%, p = 0.01) of severely depressed (/=30 days after primary percutaneous coronary intervention and had LV ejection fractions 1.3 (n = 68). Patients with CFR 1.3. CFR was significantly correlated with the LV ejection fraction at 4 weeks (r = 0.50, p <0.0001) and LV end-diastolic volume at 4 weeks (r = -0.43, p <0.0001). Kaplan-Meier survival analysis showed a higher incidence of adverse cardiac events in patients with CFR 2.5-mm DES (Cypher or Taxus) under intravascular ultrasound guidance without postdilation, using 3 implantation strategies, were studied: (1) direct stenting without predilation (n = 145), (2) predilation with a conventional semi-compliant balloon (n = 117), and (3) predilation with the AngioSculpt balloon (n = 37). Stent expansion was defined as the ratio of intravascular ultrasound-measured minimum stent diameter and minimum stent area to the manufacturer's predicted stent diameter and area. These ratios were larger after AngioSculpt predilation, and a greater percentage of stents had final minimum stent areas >5.0 mm(2) (another commonly accepted criterion of adequate DES expansion). Lesion morphology, stent and lesion length, and reference vessel size did not affect DES expansion. In conclusion, in this observational, nonrandomized study, pretreatment with the AngioSculpt balloon enhanced stent expansion and minimized the difference between predicted and achieved stent dimensions. PMID- 17719326 TI - Detailed intravascular ultrasound analysis of Zotarolimus-eluting phosphorylcholine-coated cobalt-chromium alloy stent in de novo coronary lesions (results from the ENDEAVOR II trial). AB - Zotarolimus-eluting phosphorylcholine-coated cobalt-chromium alloy Driver stents (ZES) demonstrated significant reductions in target lesion revascularization rate with few apparent adverse events compared with bare metal stents (BMS; uncoated Driver stents) in a prospective, multicenter, double-blind, randomized controlled trial in de novo coronary lesions. The aim of this study was to examine detailed vascular responses to ZES compared with BMS using serial intravascular ultrasound analysis. A total of 343 patients (ZES n = 178, BMS n = 165) were enrolled in this formal, prespecified intravascular ultrasound substudy of the Randomized Controlled Trial to Evaluate the Safety and Efficacy of the Medtronic AVE Zotarolimus-Eluting Driver Coronary Stent in de Novo Native Coronary Artery Lesions (ENDEAVOR II), a prospective, multicenter, double-blind, randomized controlled trial to compare ZES and BMS in de novo native coronary artery lesions. Quantitative and qualitative intravascular ultrasound analyses were performed postprocedurally and at 8-month follow-up in stented and reference segments. ZES showed significantly less neointima, with a larger lumen than BMS at 8 months (percentage neointimal volume 17.6 +/- 10.1% vs 29.4 +/- 17.2%, p <0.0001; maximum percentage neointimal area 32.9 +/- 13.0% vs 47.6 +/- 18.6%, p <0.0001; minimum luminal area 4.9 +/- 1.6 vs 4.0 +/- 1.7 mm(2), p <0.0001) and no unfavorable edge effect. In the 18-mm single stents, ZES showed evenly inhibited neointima compared with BMS. Neither persistent stent-edge dissection nor late acquired incomplete stent apposition was observed in either group. In conclusion, ZES showed evenly inhibited neointima with no apparent adverse vascular response in stented and reference segments at 8 months compared with BMS. PMID- 17719327 TI - Effect of glucagon-like peptide-1 (GLP-1) on glycemic control and left ventricular function in patients undergoing coronary artery bypass grafting. AB - Increasing evidence suggests that tight glycemic control improves clinical outcomes after coronary artery bypass grafting (CABG). However, the risk for hypoglycemia with insulin often results in less aggressive glycemic control. Glucagon-like peptide-1 (GLP-1) is a naturally occurring peptide whose insulinotropic effects are predicated on the glucose concentration, minimizing the risk for hypoglycemia. This study was conducted to examine whether perioperative treatment with GLP-1 would affect glycemic control and improve hemodynamic recovery after CABG. Twenty patients with coronary heart disease and preserved left ventricular function who were scheduled to undergo CABG were randomized to receive standard therapy at the discretion of the surgeon or treatment with GLP-1 (1.5 pmol/kg/min) as a continuous infusion beginning 12 hours before CABG and continuing for 48 hours. Perioperative hemodynamics, the left ventricular ejection fraction, plasma glucose, and requirements for insulin drips and inotropic support were monitored. There were no differences between groups in the preoperative, postoperative, or 7-day left ventricular ejection fraction (GLP-1 61 +/- 4%, control 59 +/- 3%) or cardiac index at 18 hours (GLP-1 3.0 +/- 0.2 L/min/m(2), control 3.3 +/- 0.4 L/min/m(2)). However, the control group required greater use of inotropic and vasoactive infusions during the 48 hours after the operation to achieve the same hemodynamic result. There were also more frequent arrhythmias requiring antiarrhythmic agents in the control group. GLP-1 resulted in better glycemic control in the pre- and perioperative periods (GLP-1 95 +/- 3 mg/dl, control 140 +/- 10 mg/dl, p /=160 mg/dl (n = 76; 17%). Overall, CAC was observed in 190 men (40%). The prevalence of CAC >0 was lowest in MS-negative men with LDL cholesterol <130 (35%) or 130 to 159 mg/dl (34%) and highest in MS-positive men with LDL cholesterol >/=160 mg/dl (80%). MS-positive men with LDL cholesterol of 130 to 159 mg/dl had CAC prevalence similar to that of MS-negative men with LDL cholesterol >/=160 mg/dl (54% vs 57%, respectively). This relation persisted with additional adjustment for age, smoking status, and cholesterol-lowering medication. In logistic regression analyses, the odds ratio for CAC >0 was highest in MS-positive men combined with high LDL cholesterol. In conclusion, these results suggest that the risk of CAC in asymptomatic men with moderate or high LDL cholesterol is magnified in persons with MS. PMID- 17719331 TI - Comparison of the prognostic significance of the electrocardiographic QRS/T angles in predicting incident coronary heart disease and total mortality (from the atherosclerosis risk in communities study). AB - Spatial QRS/T angle and spatial T-wave axis were shown to be strong independent predictors of incident coronary heart disease (CHD) and total mortality, but they are not routinely available. We evaluated whether frontal plane QRS/T angle, easily obtained as the difference between frontal plane axes of QRS and T, provides a suitable substitute for spatial QRS/T angle as a risk predictor. Our study consisted of 13,973 participants from the ARIC Study. Outcome variables were incident CHD and total mortality during a median follow-up of 14 years. Electrocardiographic variables were categorized as abnormal (>/=95th percentile), borderline (>/=75th and <95th percentile), and normal (<75th percentile) separately for men and women. Cox regression was used to assess the effect of electrocardiographic variables on risk of each outcome. The normal category was considered the reference cell. With adjustment for demographic and clinical characteristics, both QRS/T angles were approximately equally strong predictors of total mortality with >50% increased risk. Spatial QRS/T angle was a stronger predictor of incident CHD in women, with a 114% increased risk, but it was not significantly associated with risk of incident CHD in men. Similarly, frontal plane QRS/T angle was statistically significant for only women with a 74% increased risk of incident CHD. In conclusion, frontal plane QRS/T angle as an easily derived risk measure is a suitable clinical substitute for spatial QRS/T angle for risk prediction. PMID- 17719332 TI - Long-term prognostic value of p-wave characteristics for the development of atrial fibrillation in subjects aged 55 to 74 years at baseline. AB - Atrial fibrillation (AF) is the most prevalent arrhythmia in the elderly, associated with high mortality and morbidity rates. Changes in electrocardiographic P waves were associated with AF in patient series, but the long-term prognostic value of P-wave characteristics in the development of AF was not shown. The aim was to evaluate P-wave duration and morphologic characteristics as potential independent risk markers for the long-term development of AF in the general population. A nested case-control design was adopted in subjects aged 55 to 74 years and apparently healthy at baseline. Baseline P-wave items of 40 patients who developed AF within the 10-year period were compared retrospectively with those of 120 matched controls. Broad maximum P waves (>/=120 ms) at baseline were observed in 70% of patients with AF and 41% of controls (p = 0.002). Maximum P-wave duration proved to be a significant risk marker independent of blood pressure, body mass index, and other electrocardiographic findings. However, this association seems overruled by the predictive value of morphologic changes defined as notched or deflected P waves (p = 0.0002). The joint occurrence of longer duration in combination with morphologic changes in the P wave proved a very important risk indicator for the development of AF over 10 years, with an adjusted odds ratio of 13.4 (95% confidence interval 3.3 to 46.6). In conclusion, enhanced clinical appreciation of P-wave items on the standard electrocardiogram at rest, preferably evaluated in all 12 leads, may help identify a group at high risk of the development of AF at an early stage. PMID- 17719333 TI - Effect of hemoglobin levels on cardiovascular outcomes in patients with isolated systolic hypertension and left ventricular hypertrophy (from the LIFE study). AB - The optimal hemoglobin level in patients with hypertension or heart failure is not yet defined. The aim of the present investigation was to examine the relation of hemoglobin with cardiovascular outcomes in high-risk patients with isolated systolic hypertension (ISH) and left ventricular hypertrophy (LVH). In 1,326 patients with ISH in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study, hemoglobin and cardiovascular outcomes were examined using Cox proportional hazard models. Baseline hemoglobin was negatively related to rate of cardiovascular death (hazard ratio 0.81 per 1 g/dl, 95% confidence interval [CI] 0.67 to 0.98, p = 0.032) after adjusting for baseline Framingham risk score, LVH, treatment, and estimated glomerular filtration rate. Hemoglobin decreased slightly during the study and the decrease was more pronounced in the losartan group (13.9 +/- 1.3 to 13.6 +/- 1.4 g/dl) than in the atenolol group (13.9 +/- 1.2 to 13.8 +/- 1.4 g/dl). Hemoglobin as a time-varying covariate was negatively associated with rate of cardiovascular death (hazard ratio 0.75, 95% CI 0.63 to 0.90, p <0.001) and stroke (hazard ratio 0.84, 95% CI 0.72 to 0.99, p = 0.040) after adjusting for baseline Framingham risk score, LVH, treatment, and estimated glomerular filtration rate. In conclusion, in this high-risk population with ISH and LVH, lower hemoglobin at baseline was associated with higher probability of cardiovascular death, and decrease in hemoglobin over time was associated with higher probability of cardiovascular death or stroke; this effect was attenuated by treatment with losartan. PMID- 17719334 TI - Diagnostic usefulness and prognostic implications of the mitral E/E' ratio in patients with heart failure and severe secondary mitral regurgitation. AB - In patients with chronic heart failure (CHF) and severe secondary mitral regurgitation (MR), the diagnostic usefulness and prognostic impact of tissue Doppler imaging (TDI) is unknown. This prospective study enrolled 370 patients with stable CHF. Severe secondary MR, defined as effective regurgitant orifice area >/=0.20 cm(2), was present in 92 patients (25%). Echo measurements comprised left ventricular volumes, ejection fraction, mitral E/A ratio, deceleration time, and TDI-derived mitral annular velocities (e.g., S', E', A', E/E'). During a follow-up of 790 +/- 450 days, all-cause mortality and rehospitalization data were analyzed. Patients with or without MR did not differ with respect to age or ejection fraction, but patients with MR were in a poorer New York Heart Association functional class and had a higher mitral E/E' ratio. During follow up, 70 patients (18%) died and 134 patients (36%) were rehospitalized for worsening heart failure. Mortality rate was significantly higher in patients with versus without severe MR (33% vs 14%, p <0.001). In the MR group, the mitral E/E' ratio independently predicted all-cause mortality and was also significantly associated with rehospitalization for worsening heart failure. In patients with MR with an E/E' ratio >13.5, outcome was markedly worse compared with patients with an E/E' ratio 26 ml/m(2) or presence of left ventricular hypertrophy or significant valvular heart disease. Data were obtained in 132 patients (96%) over a mean follow-up period of 26 +/- 7 months during which 19 (14%) developed major cardiac events (14 deaths and 5 HF admissions). Univariate predictors for major cardiac event were age (p = 0.05), male gender (p = 0.007), presence of clinical signs of HF (p = 0.02), NT-pro-BNP level >/=50 pmol/L (p <0.001), abnormal electrocardiogram (p = 0.02), and abnormal echocardiogram (p = 0.004). However, the only independent predictors were male gender (odds ratio 3.09, 95% confidence interval 1.01 to 9.46, p = 0.05), NT-pro-BNP level >/=50 pmol/L (odds ratio 5.78, 95% confidence interval 1.63 to 20.5, p = 0.007), and abnormal echocardiogram (odds ratio 11.1, 95% confidence interval 1.43 to 85.6, p = 0.02). In conclusion, NT-pro-BNP and abnormal echocardiogram provided independent information for predicting adverse outcome in patients with suspected HF referred from the community. PMID- 17719337 TI - Risk factors and predictors of Torsade de pointes ventricular tachycardia in patients with left ventricular systolic dysfunction receiving Dofetilide. AB - The purpose of this study was to identify risk factors of Torsade de pointes (TdP) ventricular tachycardia in patients medicated with a class III antiarrhythmic drug (dofetilide) and left ventricular systolic dysfunction with heart failure (HF) or recent myocardial infarction (MI). The 2 Danish Investigations of Arrhythmia and Mortality on Dofetilide (DIAMOND) studies enrolled patients with HF (DIAMOND-HF) or MI (DIAMOND-MI) and left ventricular systolic dysfunction. The present analysis includes only patients treated solely with dofetilide. The incidence of TdP was 2.1% (32 of 1,511). Twenty-five of the incidences occurred in the DIAMOND-HF study and 7 cases in the DIAMOND-MI study (p = 0.0015). TdP was more frequent in women than in men (47% vs 28%, p = 0.02). Risk factors for developing TdP were female gender (odds ratio 2.2, 95% confidence interval [CI] 1.0 to 5.0), MI within 8 weeks (odds ratio 0.3, 95% CI 0.1 to 0.7), being in New York Heart Association class III or IV (odds ratio 3.2, 95% CI 1.2 to 8.6), and baseline QTc duration (odds ratio 1.14, 95% CI 1.00 to 1.30) per 10 ms. Women with chronic HF, QTc duration >400 ms. and New York Heart Association class III or IV had a risk of TdP of 10%, whereas no TdP episodes were observed in patients with QTc duration <400 ms. In conclusion, severity of HF, female gender, and QTc duration make it possible to identify patients with a high risk of early TdP when treated with dofetilide. Patients with recent MI less often had TdP compared with patients with chronic HF. PMID- 17719338 TI - Effect of a single 20-mg tablet of Atorvastatin on brachial artery blood flow in normolipidemic male smokers versus nonsmokers. AB - This study evaluated the acute effect of statin administration in smokers. We conducted a prospective study to determine the acute effect (24 hours) of single dose atorvastatin (20 mg) on brachial artery endothelial function using vascular ultrasonography (flow-mediated vasodilation [FMD]) and blood flow in normolipidemic smokers (10 men, 42 +/- 9 years of age) and healthy nonsmokers (10 men, 39 +/- 7 years of age). Atorvastatin increased brachial artery percent FMD in smokers from 4.1 +/- 1.4% to 5.7 +/- 1.7% (p <0.0005), whereas we found no significant change after atorvastatin in nonsmokers (from 5.8 +/- 1.2% to 5.9 +/- 1.2%, p = NS). The velocity time integral also showed a significant increase as percent FMD in smokers 24 hours after taking atorvastatin (from 19 +/- 11 to 25 +/- 12 cm, p <0.05), whereas no significant change occurred in nonsmokers (from 18 +/- 9 to 19 +/- 10 cm, p = NS). Baseline brachial artery diameter significantly dilated in smokers after taking atorvastatin compared with before taking atorvastatin (from 4.23 +/- 0.5 to 4.35 +/- 0.4 mm, p <0.05), but did not change in nonsmokers (from 4.26 +/- 0.6 to 4.31 +/- 0.6 mm, p = NS). In conclusion, single-dose atorvastatin restores endothelial function and increases brachial artery blood flow in normolipidemic men smokers within 24 hours. These findings suggest early benefits of statin therapy on endothelial function in smokers. PMID- 17719339 TI - Frequency and cause of cardiac troponin T elevation in chronic hemodialysis patients from study of cardiovascular magnetic resonance. AB - Cardiac troponin T level predicts a gradient risk for death in patients using hemodialysis. We used cardiovascular magnetic resonance (CMR) to determine whether an asymptomatic increase of troponin T in patients using hemodialysis is associated with subclinical myocardial infarction (MI). Twenty-six patients using long-term hemodialysis (49 +/- 12 years of age, 19 men, 8 diabetics) with left ventricular (LV) ejection fraction >40% and no known coronary artery disease were selected based on a low-risk troponin T level /=0.07 ng/ml (median 0.15, interquartile range 0.09 to 0.19, n = 13). All underwent CMR imaging for LV mass and for MI by late gadolinium enhancement. Between high- and low-risk patients using hemodialysis, there were no differences in age, gender, ethnicity, or diabetes mellitus. Of the high-risk patients, 3 (23%, 95% confidence interval [CI] 5 to 54) had MI by late gadolinium enhancement versus 0 (0%, 95% CI 0 to 25) low-risk patients (p = 0.22). A diffuse, midwall late gadolinium enhancement pattern was seen in 1 high-risk patient (8%) versus 0 low risk patient (0%, 95% CI 0 to 25, p = 0.97). Height-adjusted LV mass and LV hypertrophy were not significantly different between high-risk (62 +/- 26 g/m(2.7), LV hypertrophy, n = 7, 54%) and low-risk (54 +/- 20 g/m(2.7), LV hypertrophy, n = 5, 39%) patients (p = 0.37 for LV mass, p = 0.69 for LV hypertrophy). In conclusion, MI detected by CMR is present in few patients on hemodialysis with high troponin T levels and absent in the setting of very low troponin T levels, suggesting that additional myocardial pathologies cause increased troponin T in patients using hemodialysis. PMID- 17719340 TI - Heart rate variability and heart rate turbulence in patients with type 2 diabetes mellitus with versus without cardiac autonomic neuropathy. AB - Cardiac autonomic neuropathy (CAN) is an important complication of diabetes mellitus (DM) and confers an increased cardiovascular risk. The aim of this study was to disclose the place of heart rate (HR) variability and HR turbulence for the detection of CAN in patients with type 2 DM and no obvious heart disease. Ninety patients who were <75 years old and had type 2 DM for >/=2 years were studied. CAN was diagnosed with a battery of cardiovascular reflex tests and the degree of neuropathic involvement was graded by the Ewing score. Time-domain HR variability and HR turbulence parameters were assessed on 24-hour digital Holter recordings. Thirty-five patients were found to have CAN. The clinical characteristics of patients with and without CAN were similar, except that the mean duration of DM and the number of patients using insulin were significantly increased in the group with CAN. All time-domain HR variability parameters were significantly lower in the group with CAN. Of the 2 HR turbulence parameters studied, turbulence onset was similar but turbulence slope was significantly lower in the group with CAN. The Ewing score significantly correlated negatively with all HR variability parameters and turbulence slope, and among all, turbulence slope was the most strongly correlated (r = -0.617, p <0.01). Receiver operating characteristics analysis revealed a sensitivity of 97% and a specificity of 71% at a turbulence slope cut-off value of 3.32 for the detection of CAN. In conclusion, time-domain HR variability and HR turbulence parameters, except turbulence, onset were found to be significantly depressed in patients with type 2 DM and CAN. Decreases in all these parameters were found to correlate significantly with degree of neuropathic involvement. The most strongly correlated parameter, turbulence slope, was found to be highly sensitive and specific for the detection of CAN at a cut-off value of 3.32. PMID- 17719341 TI - Quantitative estimation of left atrial linear dimension on a transthoracic echocardiogram using an electrocardiographic formulaic assessment. AB - A proportionate and incremental association between left atrial (LA) dilatation on a transthoracic echocardiogram (TTE) and increasing severity in abnormal atrial depolarization can be described by the regression formula: LA dimension in parasternal long-axis view (in millimeters) = 2.47 + 0.29 [P-wave duration (in milliseconds)]. However, prospective testing of this formula for LA quantification with comparison to other TTE indexes is lacking. We prospectively obtained 12-lead electrocardiograms for 72 consecutive patients before individual, nonemergent TTE assessment. P waves were assessed independently to the nearest 10 ms for application of the formula with a Bland-Altman plot. P-wave durations were obtained specifically from lead II and also from any lead that yielded the widest measurement. There was a strong formulaic correlation with LA measurement by TTE (p <0.00000001; r = 0.662), irrespective of electrocardiographic lead used. However, as the measurement difference increased between that in any lead and lead II, correlation strength increased. Correlation was not significantly affected by commonly measured electrocardiographic and TTE indexes, such as, PR interval, QRS complex, and left ventricular end-diastolic as well as systolic dimensions, after adjustment for these variables. Moreover, when the P-wave axis remained within the normal range, the correlation strength increased. The Bland-Altman plot also showed good agreement of LA dimension assessment between formulaic estimation and TTE measurement. In conclusion, there is good agreement and correlation between formulaic estimation and that of TTE for measurement of LA linear dimension. The LA regression formula is an indirect asset that could perhaps supplement LA quantification on TTE in certain circumstances. PMID- 17719342 TI - Postprandial hyperglycemia/hyperlipidemia (postprandial dysmetabolism) is a cardiovascular risk factor. AB - Epidemiologic data indicate that a postprandial state characterized by abnormally increased levels of glucose and lipids (also referred to as postprandial dysmetabolism) is an independent predictor of future cardiovascular events, even in nondiabetic subjects. The cardiovascular toxicity of postprandial dysmetabolism is mediated by oxidant stress, which is directly proportional to the increase in glucose after a meal. This transient increase in free radicals acutely triggers inflammation, endothelial dysfunction, hypercoagulability, sympathetic hyperactivity, and a cascade of other atherogenic changes. The postprandial dysmetabolism hypothesis has been bolstered by interventional studies that have demonstrated that blunting the postprandial spikes in glucose and lipids improves inflammation and endothelial function immediately. Early randomized controlled trials indicate that reducing postprandial dysmetabolism appears to significantly slow atherosclerotic progression and may improve cardiovascular prognosis. In conclusion, postprandial dysmetabolism appears to be an important proximate cause of adverse cardiovascular events. Addressing this fundamental and largely unrecognized condition will require specific screening and treatment strategies. Diet, exercise, and various pharmacologic agents can improve postprandial dysmetabolism. Using these strategies may help improve the prognosis for patients with diabetes mellitus and/or coronary heart disease. PMID- 17719343 TI - Patent foramen ovale closure devices: thoughts from the circulatory device advisory panel. PMID- 17719344 TI - A new perspective on nonprescription statins: an opportunity for patient education and involvement. AB - Education of the public and encouragement of patients' involvement in their own health care have been repeatedly proved effective means of increasing health awareness, promoting lifestyle modifications, and improving early disease detection in a variety of clinical scenarios. Despite substantial efforts from different public and private organizations to educate the population on cardiovascular risk, coronary heart disease remains the leading cause of death in the United States, and its prevalence continues to grow. Therefore, alternative approaches with the potential to elicit a meaningful impact in the community deserve consideration. A nonprescription statin program could provide consumers with a tool of proved benefit in cardiovascular risk prevention. The magnitude of the target population (millions of subjects with intermediate to high risk), as well as the safety and efficacy profile of lovastatin 20 mg, support the consideration of this drug for "over-the-counter" availability. Moreover, a nonprescription statin program could represent a unique opportunity not only to enhance patients' involvement in primary prevention but also to reinforce the education of the public and to encourage interaction with health care providers. The success of such a program will undoubtedly require precise labeling of the risks and benefits of the therapy, as well as active support and participation from major medical organizations. In conclusion, nonprescription statin availability, through enhanced unique patients' involvement, offers the potential for enormous public health benefit. PMID- 17719345 TI - Reexamining the New York Heart association functional classification of heart failure. PMID- 17719346 TI - Comment on massing report on premature ventricular complexes and coronary artery disease: historical reflection. PMID- 17719348 TI - Pharmacologic approaches to restenosis prevention. AB - Despite significant advances in technology and technique, coronary restenosis remains the primary limitation of percutaneous transluminal coronary angioplasty (PTCA). Among patients undergoing PTCA, between 20% and 50% of patients who do not receive a stent and 10%-30% of those who do receive a stent develop restenosis within 6 months of the procedure. Drug-eluting stents, which release high local concentrations of antiproliferative or immunosuppressive agents directly into the vessel wall at the site of the lesion, have dramatically reduced the incidence of restenosis in patients undergoing PTCA. However, even with drug-eluting stents, a significant percentage of higher-risk patients develop in-stent restenosis. These data suggest that a role remains for effective, well-tolerated systemic pharmacologic therapies to further reduce the rate of restenosis. To date, the majority of systemic agents tested for restenosis prevention have failed to show significant benefit. Only 2 agents, probucol and cilostazol, have consistently demonstrated efficacy in preventing restenosis. In addition, the investigational agent AGI-1067 has demonstrated promising efficacy in early clinical trials. Together with drug-eluting stents, these therapies may for the first time reduce the rate of restenosis to near zero, even in high-risk patients, such as individuals with diabetes mellitus. PMID- 17719349 TI - Understanding the drug-eluting stent trials. AB - The advent of intravascular stenting dramatically reduced the incidence of restenosis among patients undergoing percutaneous transluminal coronary angioplasty. However, a substantial percentage of patients, particularly those with risk factors such as diabetes mellitus or complicated lesions, remain at risk for restenosis. Drug-eluting stents overcome this problem by releasing bioactive agents from a polymeric coating directly into the vessel wall, inhibiting the cellular mechanisms of restenosis while avoiding systemic toxicity. Recent data indicate that local targeting of the proliferative process with drug-eluting stents dramatically reduces the risk for restenosis, even among high-risk patients. A range of bioactive coatings are currently available or in late clinical trials. Both sirolimus- and paclitaxel-eluting stents have demonstrated efficacy in a broad range of patient types; early data from clinical trials of second-generation stent coatings, such as everolimus and ABT-578 (zotarolimus), suggest that these agents are also effective in preventing restenosis. This article reviews the pathophysiology of in-stent restenosis and surveys recent key clinical trials of drug-eluting stents. PMID- 17719350 TI - Applying drug-eluting stents in clinical practice. AB - The use of percutaneous coronary interventions has resulted in significant improvement in patient care; however, the risk for restenosis remains a major limitation. Drug-eluting stents represent an impressive breakthrough in the evolution of interventional cardiology, but it is important to understand the limits to their added benefit. Safety of the procedure must continue to be the first consideration, and technique must not be compromised to accommodate new technology. PMID- 17719351 TI - The pathophysiology and burden of restenosis. AB - The introduction of percutaneous transluminal coronary angioplasty (PTCA) revolutionized the surgical treatment of coronary artery disease. However, despite increased surgical experience and technical breakthroughs, restenosis occurs in 30%-50% of patients undergoing simple balloon angioplasty and in 10% 30% of patients who receive an intravascular stent. Animal and human data indicate that restenosis is a response to injury incurred during PTCA. The need for reintervention in a high percentage of patients due to restenosis remains an important limitation to the long-term success of PTCA. Stenting reduces initial elastic recoil and limits negative arterial remodeling; however, bare-metal stents may promote intimal hyperplasia by eliciting an immune and proliferative response. Consistent with these data, clinical studies suggest that drug-eluting stents, coated with anti-inflammatory or antiproliferative agents, reduce the risk for restenosis. Stenting represents a considerable cost burden. Treatment strategy should focus on selective use of expensive drug-eluting stents in populations where they have been found to be more clinically effective than bare metal stents--patients who are at high risk for restenosis or who develop restenosis with bare-metal stents. Recent studies suggest that the pharmacologic management of restenosis is now feasible. Together, the judicious use of stents and oral pharmacotherapy promise to reduce the risk for restenosis, even among high-risk patients. PMID- 17719352 TI - [Risk stratification of acute coronary syndromes]. AB - In acute coronary syndromes, risk stratification is essential, particularly in those without ST-elevation, and is based upon clinical and biological markers. Among them, recent and repeated anginal attacks, ST-segment modifications on admission electrocardiogram, and increased markers of myonecrosis (particularly increased troponine levels) are strong predictors of untoward outcome. These variables can be used to construct risk scores, among which the TIMI and GRACE scores are the most widely used. These scores may prove helpful to define the optimal diagnostic and therapeutic management of the patients. PMID- 17719353 TI - [Epidemiology of acute coronary syndrome in Europe]. AB - Epidemiological data concerning acute coronary syndromes in Europe are based on national registries, studies by the European Society of Cardiology within the framework of the EuroHeart Survey and on the study of European population sub groups in large international cohorts. In this article, recently published studies will be reviewed, and the principal developments in different countries as well as the characteristics and particularities of the most recent epidemiological data will be highlighted. In Europe, the presentation of acute coronary syndromes (ACS) has evolved considerably over the last ten years. This evolution is characterized by a reduction in the proportion of acute coronary syndromes with ST-segment elevation (STEMI) and by ageing populations. PMID- 17719354 TI - [Management coronary syndrome in the acute phase]. AB - The clinical benefit of the combination of aspirin plus clopidogrel over aspirin alone to prevent recurrent events after acute coronary syndrome is obviously a key step of the past few years in the management of coronary artery disease. The extended benefit of this combination among patients undergoing stent implantation is another key message for clinician. The consistent benefit of the dual oral antiplatelet therapy in all clinical trials is reassuring for clinicians. However, all well designed clinical trials generate new hypothesis and unsolved clinical issues. The loading dose of clopidogrel and whether we should monitor the biological response to clopidogrel in order to improve its clinical benefit are the next clinical challenges for clinicians dealing with acute coronary syndromes. Providing adequate answers to these relevant clinical issues should improve the clinical benefit of clopidogrel. All these important points are discussed in the following manuscript. PMID- 17719355 TI - [Long-term management of post acute coronary syndrome with oral antiplatelet therapy]. AB - Cardiovascular disease is the primary cause of early death and morbidity in the industrialized world and is becoming a growing problem in many developing countries. Coagulation inhibitors play a major role in the management of the acute phase of ACS whether in association with reperfusion strategies or not. Currently, and in accordance with the results of major randomised studies, for medium and long-term management, the association of Clopidogrel and aspirin is the treatment of choice. However, despite the recognised benefits of this therapeutic strategy and above all the recommendations of learned societies, which have placed this bi-therapy in class I, according to national and international registries it is still underused. Moreover, all of these registries have confirmed, in the real world, the negative impact of not prescribing this antiplatelet therapy on morbidity and mortality after both ST and non-ST elevation acute coronary syndrome. which shows the difficulty of applying to everyday clinical practice the results of major randomised cohorts. PMID- 17719356 TI - [Epidemiology of acute coronary syndrome in France]. AB - Coronary artery disease remains a major cause of death in France. Epidemiology of acute coronary syndromes (ACS) encompasses the study of trends of mortality, incidence and case fatality. Methodology includes data from populational and hospital registries of ACS. Incidence and mortality rates of ACS are significantly higher in the North than in the South of France. Significant improvement of ACS mortality and hospital case fatality were registered from 1997 to 2002. However, a slow down in ACS incidence rates was shown during the same period and particularly in the South of France. Sudden death continues to be a major health concern due to problems of prevention. Pre-hospital management is also a major source of health inequalities and this merits further analysis of those disparities. Recent data have shown large improvement in acute coronary care but the relatively high rates of ACS incidence stress the need to promote primary prevention and the screening of minor atherosclerosis lesions. PMID- 17719357 TI - Social determinants of women's mental health. PMID- 17719358 TI - Comparison of four common stressors across the breast cancer trajectory. AB - OBJECTIVE: Studies of cancer stressors have typically assessed a limited number of factors using cross-sectional designs. There is little information about aspects of cancer that patients consider most stressful at different points along the disease trajectory. METHODS: Seventy-two breast cancer patients rated the degrees to which they experienced each of four common cancer concerns as stressful during the preceding month at 3, 7, 11, and 15 months, and at 6 years after diagnosis. Stressors included fear of the future; physical limitations; pain; and problems with family or friends due to cancer. RESULTS: Overall, the cancer concerns were rated as not especially stressful, with the exception of fear of the future which was the most stressful of the four concerns on all measurement occasions. Although fear of the future decreased from 3 to 7 months following diagnosis, it remained elevated at all of other time points. Physical limitations and pain were reported to induce equivalent levels of stress and their intensities decreased over time. However, there was a resurgence of the stressfulness of physical limitations and pain at the 6-year follow-up point when women experienced a second cancer during the long-term follow-up period. At all measurement occasions, breast cancer survivors reported very low levels of concern in relation to family and friends. CONCLUSION: Breast cancer can be stressful for years after diagnosis for some women and especially for those who experience a second cancer. Fear of the future is the most pressing target for psychosocial interventions. PMID- 17719359 TI - Stress history and breast cancer recurrence. AB - BACKGROUND: There is mixed evidence regarding the possible association between a history of stressful or traumatic life events and more rapid breast cancer progression. METHOD: Retrospective reports of past experiences of traumatic life events were assessed among 94 women with metastatic or recurrent breast cancer. A traumatic event assessment was conducted using the event-screening question from the posttraumatic stress disorder (PTSD) module of the Structured Clinical Interview for the DSM-IV-TR (SCID; 2002). Each reported event was judged by two independent raters to determine whether it met DSM-IV-TR PTSD A1 criteria for a traumatic event. Those events that did not meet such criteria were designated "stressful events." RESULTS: Nearly 42% of the women in the sample were judged to have experienced one or more traumatic events; 28.7% reported only stressful events. A Kruskal-Wallis test found significant differences in disease-free interval among the three groups [chi2 (2, N=94)=6.09, P<.05]. Planned comparisons revealed a significantly longer disease-free interval among women who had reported no traumatic or stressful life events (median=62 months) compared to those who had experienced one or more stressful or traumatic life events (combined median=31 months). CONCLUSIONS: A history of stressful or traumatic life events may reduce host resistance to tumor growth. These findings are consistent with a possible long-lasting effect of previous life stress on stress response systems such as the hypothalamic-pituitary-adrenal (HPA) axis. PMID- 17719360 TI - Do single and partnered women with gynecologic cancer differ in types and intensities of illness- and treatment-related psychosocial concerns? A pilot study. AB - OBJECTIVE: We compared the psychosocial and psychosexual concerns of single and partnered women with gynecologic cancer, since relationship status and psychosocial context are known to affect sexuality, a life domain commonly affected by this cancer. METHOD: A cross-sectional convenience sample of 49 women (68% response), with ovarian (n=31), endometrial (n=12), and cervical (n=6) cancer, responded to a 72-item self-report Cancer Concerns Questionnaire and additional psychosocial questionnaires. RESULTS: Single (n=13) and partnered women (n=36) similarly reported prognosis as their highest concern, but single women (26% of the sample) reported that communication with the treatment team, treatment side effects, and prognosis were of greater salience to them than did partnered women. The latter group had greater sexuality and partner relationship concerns. CONCLUSION: These preliminary findings suggest that relationship status, whether partnered or single, influences current psychosocial concerns among women with gynecologic cancer, despite similar levels of illness- and treatment-related intrusions on important life domains. PMID- 17719361 TI - Does dispositional optimism predict psychological responses to counseling for familial breast cancer? AB - OBJECTIVE: The present study sought to assess the ability of dispositional optimism to predict the psychological responses of women with a family history of breast cancer who had been referred to counseling for familial breast cancer. METHODS: Women completed questionnaires prior to (n=735), immediately after (n=655), and 9 months after (n=545) attending counseling. Breast cancer risk status was assessed and communicated to the women in the clinics. RESULTS: Dispositional optimism was found to predict lower levels of anxiety and breast cancer worries immediately following counseling as well as lower levels of anxiety and perceived risk at 9-month follow-up, controlling for corresponding baseline scores. In addition, risk status moderated the optimism-perceived risk relationship, such that optimism was only predictive of lower risk perceptions among women at high risk. CONCLUSIONS: Low levels of dispositional optimism may be considered to be a risk factor for adverse reactions to high breast cancer risk information. The implications of the findings for the clinical management of such reactions are discussed. PMID- 17719362 TI - Relationships with clinical staff after a diagnosis of breast cancer are associated with patients' experience of care and abuse in childhood. AB - OBJECTIVE: Patients experiencing the crisis of the diagnosis and treatment of breast cancer need to form trusting and supportive relationships with clinical staff. However, adverse childhood experiences damage the ability to form supportive relationships as adults. We tested the prediction that women recalling childhood abuse and lack of parental care would experience poorer support from clinical staff caring for them around the time of diagnosis and surgical treatment of breast cancer. METHODS: Two to 4 days after surgery, women with primary breast cancer (N=355) self-reported: childhood sexual, physical, and emotional abuse and parental care; perceived social support; support experienced from the surgeon and breast and ward nurses; and current emotional distress. Logistic regression analyses and covariance structure modeling tested the dependence of perceived professional support on childhood abuse and care and on current social support, controlling for emotional distress and age. RESULTS: Women who reported feeling fully supported by clinical staff were more likely to recall no abuse and good parental care. The influence of parental care, but not abuse, was explained by its association with experiencing good social support generally, which was itself associated with feeling fully supported by clinical staff. These relationships were independent of current emotional distress. CONCLUSION: Patients' ability to feel fully supported by clinical staff reflects not only how much support staff make available but also patients' experience of close relationships in childhood. We suggest that, whereas lack of parental care compromises adult supportive relationships in general, abuse specifically reduces support from clinical staff. PMID- 17719363 TI - Correlates of depressive symptoms among women undergoing the menopausal transition. AB - OBJECTIVE: Studies indicate that approximately 25% of women undergoing the menopausal transition experience depressive symptoms. The purpose of this study was to examine whether menopausal status was associated with the experiencing of depression among midlife women, to assess which demographic and health habit characteristics were associated with depressive symptoms experienced during the menopausal transition, and to analyze the associations between hormone levels and depressive symptoms. METHODS: Data from a community-based sample of 634 women aged 45 to 54 years were analyzed. Each participant completed a questionnaire and provided a blood sample that was used to measure estrogen and androgen concentrations by enzyme-linked immunosorbent assay. Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression Scale (CES-D). RESULTS: Approximately 25% of the women in the study were experiencing depressive symptoms (CES-D >or=16). The data showed that being a current smoker, having little/no regular physical activity, being in poor health, and reporting a greater number of menopausal symptoms were independently and significantly associated with depressive symptoms. Menopausal status and the measured hormone levels were not significant independent correlates of depressive symptoms. CONCLUSIONS: These findings confirm the relatively high prevalence of depressive symptoms among midlife women and suggest that certain demographic, health habit, and menopausal symptom characteristics may be more important correlates of depressive symptoms in midlife than menopausal status and hormone levels. PMID- 17719364 TI - Hysterectomy and loss of fertility: implications for women's mental health. AB - OBJECTIVE: The objective of this study was to assess the percentage of women scheduled for hysterectomy who would have liked to have had a child or more children and associated factors. METHODS: The study sample included 1140 premenopausal women having hysterectomy for benign indications who were interviewed before and after their surgery over the course of a 2-year follow-up period. The main outcome measures for this study were desire for a (or another) child measured preoperatively; concurrent measures of psychological distress, including anxiety, depression, anger, and confusion, and seeking of professional help for emotional problems; and psychological distress measured 12 and 24 months postoperatively. RESULTS: Of the sample, 10.5% (n=120) answered yes to the question, "Before you were told you needed a hysterectomy, would you have wanted a (or another) child?" As compared with those who did not, those who desired a (another) child were younger; more likely to be nulliparous; waited longer before having surgery; were more likely to have an indication of endometriosis; had higher levels of depression, anxiety, anger, and confusion; and were more than twice as likely to have seen a mental health professional for anxiety or depression in the 3 months before their surgery. These differences in psychological distress persisted over the course of the 2-year follow-up period. CONCLUSIONS: The issue of loss of fertility should be discussed candidly with women considering hysterectomy, and those who express ambivalence, sadness, or regret at the loss of future childbearing options may benefit from further exploration of fertility-sparing treatments. PMID- 17719365 TI - Psychometric evaluation of health-related quality of life measures in women after different types of delivery. AB - OBJECTIVE: We examined the psychometric properties of three internationally established measures for health-related quality of life (HRQoL) in women after vaginal delivery (VD), elective cesarean section (CS), and emergency CS and the relationship of HRQoL scores with blood loss after delivery. METHODS: This is a prospective longitudinal study. One hundred forty-one consecutive patients (71 after VD, 36 after elective CS, and 34 after emergency CS) were enrolled in two university hospitals and one general hospital from June 2003 to March 2004. Women completed the Multidimensional Fatigue Inventory (MFI) and the EQ-5D classification of own health between 12 and 24 h after VD or between 24 and 48 h after CS. Subsequent assessments, additionally including the Short Form 36 (SF 36), were made 1, 3, and 6 weeks after delivery. We analyzed feasibility (response, completion time, reported difficulties, item nonresponse), reliability (Cronbach's alpha), discriminative validity between groups by type of delivery, and responsiveness over time (Wilcoxon's signed rank tests and effect sizes). RESULTS: The MFI, SF-36, and EQ-5D proved to be highly feasible and reliable (alpha>.7 for all scales of MFI and SF-36). The measures were able to discriminate between groups by mode of delivery and to detect moderate recovery in physical and small recovery in mental status over time in the first 6 weeks after delivery. The suboptimal total questionnaire response of 60% after 6 weeks was attributable to low response among women of non-Dutch ethnic origin. The significant correlation between Hb level and mean physical HRQoL scores found at T=0 disappeared 1 week postpartum. CONCLUSION: The combination of MFI, SF-36, and EQ-5D showed good psychometric performance and is a good choice to measure HRQoL after delivery in scientific studies. Development of a shorter set is needed for use in routine clinical practice. PMID- 17719366 TI - The influence of medical and psychological interventions on women's distress after miscarriage. AB - OBJECTIVE: The aim of this study was to examine the impact of medical and psychological interventions on women's distress after early miscarriage. METHODS: This was a prospective study of women attending for a routine scan at 10-14 weeks of gestation and found to have a missed miscarriage. An intervention group of 66 women had medical investigations to ascertain the cause of miscarriage, and at 5 weeks after the scan, they all had a medical consultation to discuss the results of the investigations. These 66 women were randomly allocated into a group which received further psychological counselling (MPC, n=33), and a group which received no psychological counselling (MC, n=33). They were compared to a control group of 61 women who received no specific postmiscarriage counselling. All participants completed preintervention and postintervention measures and 4-month follow-up questionnaires. RESULTS: The scores on the outcome variables decreased significantly with time for all three groups. In group MPC, compared to controls, there was a significantly greater decrease over time in the levels of grief, self blame, and worry and, compared to MC group, a significantly greater decrease in grief and worry. In group MC, compared to controls, there was a significantly greater decrease in self-blame. In the MC and MPC groups, those with an identified cause of the miscarriage had significantly lower levels of anxiety and self-blame over time than those with a nonidentified cause. CONCLUSIONS: Psychological counselling, in addition to medical investigations and consultation, is beneficial in reducing women's distress after miscarriage. However, absence of an identifiable cause of miscarriage led to the maintenance of the initial anxiety levels, which should have otherwise decreased with time. PMID- 17719367 TI - Ethnicity, psychosocial risk, and perinatal depression--a comparative study among inner-city women in the United Kingdom. AB - OBJECTIVE: The objective of this study was to explore the relationships between psychosocial risk, ethnicity, and prevalence of depressive symptoms in the perinatal period. A comparative study among a cohort of Black Caribbean and White British women was undertaken. METHODS: A predominantly inner-city sample (N=301) was recruited at a large teaching hospital and at community antenatal clinics in the north of England. Women were screened for depressive symptoms in the last trimester of their pregnancy and 6 weeks their delivery with the Edinburgh Postnatal Depression Scale (EPDS). RESULTS: Black Caribbean women reported higher levels of psychosocial risk for perinatal depression compared with their White British counterparts. They were more socially and socioeconomically deprived. To elaborate, the Black Caribbean women were more likely to live in the most deprived areas of the city (P=.002), to live on benefits (P=.014), and to be lone parents (P<.0001). However, despite higher levels of deprivation and other known risks for perinatal depression, Black Caribbeans were not more likely than White British women to score above the threshold on the EPDS (cutoff point, 12/13). CONCLUSIONS: During and after pregnancy, approximately a quarter of the Black Caribbean women in this study recorded symptom scores suggestive of clinically significant morbidity. These findings are not reflected in clinical practice, suggesting that there may be substantial levels of undetected and untreated perinatal depression among this ethnic group. This has potentially serious implications not only for the mental health and well-being of individual women but also for their families. PMID- 17719368 TI - Eating disorders symptoms in pregnancy: a longitudinal study of women with recent and past eating disorders and obesity. AB - OBJECTIVE: To determine the impact of pregnancy on eating disorders (ED) symptoms using data from a large prospective, community-based cohort study. METHODS: Women (12,254) were classified according to whether they had a recent or past history of ED, were obese before pregnancy, or constituted part of the general population control group. We evaluated self-induced vomiting (SIV), laxative use, exercise behavior, and appraisals about weight gain during pregnancy, as well as dieting, and shape and weight concern before and during pregnancy. RESULTS: Women with a recent episode of ED dieted, used laxatives, reported SIV, and exercised more than other groups during pregnancy. They were also more likely to report ED cognitions in pregnancy and their weight and shape concern scores remained high during pregnancy. Women with past ED were also more likely than controls to have some ED behaviors and/or concerns about weight gain during pregnancy. CONCLUSIONS: Women with a recent ED continued to have some ED symptoms in pregnancy, albeit fewer compared to before pregnancy. Although at a lower level, women with a past history of ED also had ED symptoms in pregnancy. Screening for ED symptoms during pregnancy may provide a useful opportunity for engagement in treatment and to reduce behaviors that might be detrimental to the foetus. PMID- 17719369 TI - Diagnosis and management of enophthalmos. AB - Enophthalmos is a relatively frequent and misdiagnosed clinical sign in orbital diseases. The knowledge of the different etiologies of enophthalmos and its adequate management are important, because in some cases, it could be the first sign revealing a life-threatening disease. This article provides a comprehensive review of the pathophysiology, evaluation, and management of enophthalmos. The main etiologies, such as trauma, chronic maxillary atelectasis (silent sinus syndrome), breast cancer metastasis, and orbital varix, will be discussed. Its objective is to enable the reader to recognize, assess, and treat the spectrum of disorders causing enophthalmos. PMID- 17719370 TI - Intraocular lens power calculation in children. AB - With improving surgical technique and equipment, the acceptable age for placing an intraocular lens in infants and children is becoming younger. The tools for predicting intraocular lens power have not necessarily kept up, as current theoretical and regression intraocular lens power prediction formulas are largely based on adult eyes at axial lengths, anterior chamber depth, and keratometric values much different than those seen in infants. In addition, the adult eye has matured and is no longer growing, whereas the eyes of infants and children may continue to note changes in axial length, keratometric values, and possibly optical characteristics. Another source of error in intraocular lens power selection that is more likely to occur in pediatric patients than in adult patients is inaccuracy in measurement of axial length or keratometric power. A review of current tools and considerations for intraocular lens power prediction in infants and children is presented. PMID- 17719371 TI - Transplantation of ex vivo cultured limbal epithelial stem cells: a review of techniques and clinical results. AB - Ex vivo cultured limbal epithelial stem cells have been used successfully to treat corneal limbal stem cell deficiency. We identified 17 reports of the application of this novel cell-based therapy in humans. In addition we identified four reports of the use of culture oral mucosal epithelial cells to treat limbal stem cell deficiency. We examined these reports to discern the success rate, complication rate, visual outcome, whether there is an optimal technique and which patients are the most likely to benefit. We also discuss the different culture methods employed and the regulations governing cell banks that are providing this service. We found that the techniques used to cultivate and transplant cells varied, but that no individual method was clearly superior. The reported success rate is similar across all studies for both allografts and autografts. The clinical indications for this treatment are not clearly defined as indicated by the variety of disorders treated. Follow-up is limited and the long-term success rate is yet to be established. Nonetheless, we conclude that there is sufficient evidence to support the continued use and refinement of this procedure as a treatment for corneal stem cell deficiency. PMID- 17719372 TI - Triamcinolone acetonide in ocular therapeutics. AB - Triamcinolone acetonide has been effectively used in ocular therapeutics for over 50 years. Its use has increased dramatically in recent years for periocular and intraocular treatment of retinal vasculature disease and uveitis. This comprehensive review discusses the pharmacokinetics of triamcinolone acetonide and summarizes its uses in a number of diseases, both intraocular and extraocular. It discusses side effects and their management. Finally, it discusses the controversy over its use. PMID- 17719373 TI - Red lesions of the iris, choroid, and skin secondary to metastatic carcinoma of the thyroid: a review. AB - An 83-year-old man was seen with a history of bilateral progressive loss of vision of 1 month's duration. On examination, there was a reddish, nodular lesion adjacent to the right side of the nose. Slit-lamp examination revealed a reddish iris mass in the left eye. Ophthalmoscopic examination revealed two orange choroidal lesions in the right eye and a large subretinal hemorrhage in the posterior pole with a central reddish vascular lesion in the left eye. An excisional biopsy of the skin lesion was performed. A diagnosis of metastatic follicular thyroid carcinoma was made according to the histopathologic findings and immunohistochemistry. The patient had no known history of thyroid malignancy and a metastatic survey revealed widespread metastasis. The patient had a total thyroidectomy followed by two series of radioactive iodine ablation. The iris lesion completely resolved and the choroidal lesions in the right eye showed partial regression during the follow-up period. Ocular and skin metastasis secondary to thyroid carcinoma is uncommon. In a review of English literature we found reports of 12 clinically well-documented cases of choroidal metastasis and two cases of iris metastasis. Our case and review of the previous cases reveal that reddish/orange color is a commonly observed feature of the uveal metastasis of thyroid carcinoma. Although ocular and skin metastases from thyroid carcinoma are rare, this possibility should be considered in the differential diagnosis of reddish-colored iris and choroidal masses as well as reddish nodular lesions of the scalp, face, and neck. PMID- 17719374 TI - Optic neuritis in evolution. AB - A case of progressive optic neuropathy in a woman with a history of breast cancer is presented. Differential diagnoses including optic neuritis, infiltrative optic neuropathy, carcinomatous meningitis, and toxic optic neuropathies are discussed. Risk factors for metastatic brain lesions are also discussed. PMID- 17719375 TI - Trachoma surveys 2000-2005: results, recent advances in methodology, and factors affecting the determination of prevalence. AB - With the advent of VISION 2020 and GET 2020 inaugurated by the World Health Organization, it is timely to provide an update of the methodology employed in trachoma surveys, given that a significant number of individuals in many undeveloped and developing countries still suffer from this ophthalmic disease. The advent of Trachoma Rapid Assessment and Asymmetrical Sampling Rapid Trachoma Assessment has enabled faster identification of trachoma-endemic areas, though population-based surveys are still required prior to intervention. Research into factors affecting prevalence determination has shown that mobility, clustering, and seasonality should all be taken into account regarding survey design. In addition, recent advances in laboratory testing have given us new insight into trachoma infection patterns and a better understanding of the disease course. In this review, we examine advances in survey methodology and the results of trachoma surveys since 1999, and other issues relevant to the determination of trachoma prevalence. Based on recent findings, we recommend that pooled nucleic acid amplification testing be used to augment clinical assessment in areas where trachoma prevalence is greater than 20%. Further, we suggest that trachoma follicular and trachoma follicular or trachoma intense, as markers of the disease, be reported separately. PMID- 17719376 TI - Treatment of Co-existent occult choroidal neovascular membrane and macular hole. AB - The co-existence of a macular hole and a choroidal neovascular membrane can represent a diagnostic and therapeutic dilemma. In this noncomparative case report, we report on a patient with co-existent macular hole and choroidal neovascular membrane. The patient initially was found to have an occult choroidal neovascular membrane. The patient was not treated and the vision remained stable for almost 1 year until the patient noted further visual decline. The patient was treated with intravitreal pegaptanib and the patient's vision remained stable for 6 months. However, on follow-up the patient presented with visual decline and a full thickness macular hole was confirmed by optical coherence tomography (OCT). The patient underwent repair and vision improved with closure of the macular hole. The occult choroidal neovascular membrane remained stable with no evidence of disease progression. Fundus photos, intravenous fluorescein angiograms, and OCT were obtained before and after therapy and confirmed the diagnosis. This report highlights how the detection of co-existent macular hole and choroidal neovascular membrane may require OCT scanning. When treatment is entertained, therapy should be directed first toward the neovascular complex and then to repair the macular hole. PMID- 17719377 TI - More research is needed to support the association of AMD and stroke age-related macular degeneration and risk for stroke, by TY Wong, R Klein, C Sun, P Mitchell, D Couper, H Lai, LD Hubbard, and AR Sharrett, atherosclerosis risk in communities study. Ann Intern Med 145:98-107, 2006. PMID- 17719378 TI - Obesity surgery and hypovitaminosis A. PMID- 17719382 TI - Journal of oral and maxillofacial surgery: news you must use. PMID- 17719379 TI - Charles Bonnet, his life, and his syndrome. PMID- 17719383 TI - Exuberant foreign body giant cell reaction to a teflon/proplast temporomandibular joint implant: report of a case. PMID- 17719384 TI - Age as a risk factor for third molar surgery complications. AB - PURPOSE: The purpose of this study was to estimate the frequency of complications after third molar (M3) surgery, with age as the primary risk factor. PATIENTS AND METHODS: This was a prospective cohort study of a sample of subjects having at least 1 M3 extracted as part of the American Association of Oral and Maxillofacial Surgeons' Age-Related Third Molar Study. The predictor variables were categorized as demographic, health status, anatomic, and pathological. The outcome variable was overall complications, including both intraoperative and postoperative complications. Appropriate univariate and bivariate statistics were computed. A multiple logistic regression model was used to evaluate the simultaneous effects of multiple covariates. RESULTS: The study sample was comprised of 4,004 subjects having a total of 8,748 M3s removed. The mean age was 39.8 +/- 13.6 years, with 245 subjects (6.1%) age 25 and younger. Approximately half of the subjects were female. The overall complication rate was 19%. In bivariate analyses, age above 25 years, gender, American Society of Anesthesiologists classification, number of preoperatively identified risk factors for complication, impaction level of M3, evidence of periodontal disease, preoperative infection, and evidence of any pathology associated with M3 were associated with complications (P 25 years) appears to be associated with a higher complication rate for M3 extractions. PMID- 17719385 TI - Facial fracture repair in the traumatic brain injury patient. AB - PURPOSE: To review the surgical complications of patients who had facial fractures repairs in the setting of a traumatic brain injury (TBI). PATIENTS AND METHODS: A review of all individuals admitted with the diagnosis of TBI based on an evaluation by the neurotrauma service who also underwent facial fracture repair was performed. More than 600 charts were reviewed and 99 patients met study criteria. Univariate and mulitvariate logistic regression model analysis were performed comparing the complication rate in the immediate postoperative period to the patients' age, gender, mechanism of injury, zone of facial injury, preoperative Glasgow Coma score, presence of multisystem injury, mechanism of TBI and treatment, length of time from injury to surgical repair and length of surgical procedure. RESULTS: Of the 99 individuals studied, there was an 11% complication rate (8 minor, 3 major) in the immediate postoperative period. After univariate analysis, the length of time from injury to surgical repair, zone 1 facial injury and low Glasgow Coma score were all factors associated with increased complications. Multivariate logistic regression model analysis revealed that the odds of a patient sustaining a postoperative complication was 1.298 as the hour of procedure increased by 1 hour (95% CI, 1.065-1.582) and was 1.152 as the days of repair increased by 1 day (95% CI, 1.030-1.288). CONCLUSIONS: The overall complication rate of facial fracture repair in the TBI patient was 11%. A prolonged surgical procedure and delay in surgical repair were associated with higher complication rates as identified by multivariate logistical regression analysis. PMID- 17719386 TI - Severe third molar complications including death-lessons from 100 cases requiring hospitalization. AB - PURPOSE: In this study we investigated patients that were hospitalized due to third molar (M3) complications. Specifically we analyzed frequency, age distribution, and outcome with respect to the M3 clinical status. PATIENTS AND METHODS: We set up a prospective cohort study and included 100 subjects admitted for management of acute M3-associated complications. The clinical status of the M3 was defined as 1) prophylactic M3 removal, 2) therapeutic (nonelective) M3 removal, or 3) M3 present at the time of admission. Outcome variables were clinical infection markers (C-reactive protein, leukocyte counts) and economic parameters (treatment costs, length of hospital stay, and days of disability). Nonparametric tests were used for comparison of subpopulations (surgical vs nonsurgical, prophylaxis-related vs nonprophylaxis-related). RESULTS: One third of the 100 patients were age 40 or older. Overall 80 severe infections, 11 mandibular fractures, 3 nerve injuries, 5 tooth/root luxations, and 1 postoperative hemorrhage were noticed. Twenty-seven complications resulted from prophylactic surgery, 44 from nonelective removal, and 29 from pericoronitis. Postoperatively, a 77-year-old male patient hospitalized with nonelective removal sustained fatal myocardial infarction. Treatment costs were 260,086 euro (mean 2,608 euro/case); total days of disability were 1,534. The postsurgical complications showed higher C-reactive protein values compared with pericoronitis induced complications. CONCLUSIONS: Within the catchment area of our institution, the majority of complications requiring hospitalization resulted from diseased third molars or their removal. Side effects of observational strategies such as the shifting of complications to higher ages deserve future attention. PMID- 17719387 TI - Neurosensory disturbance of the inferior alveolar nerve after bilateral sagittal split osteotomy: a systematic review. AB - PURPOSE: The evaluation of neurosensory disturbance of the inferior alveolar nerve (IAN) can be performed by purely subjective, relatively objective, or purely objective methods. The aim of this study was to provide a systematic review of the incidence of inferior alveolar nerve sensory disturbance after bilateral sagittal split osteotomy, as well as the frequency of recovery of sensory function using objective methods of evaluation only. MATERIALS AND METHODS: Searches were conducted employing MEDLINE, Scirus, and the Cochrane Central Register of Controlled Trials (CENTRAL). Seven studies were included in this review. RESULTS: This systematic review has shown that the frequency of nerve impairment evaluated by subjective methods was higher than that indicated by studies adopting objective methods at each time of follow-up considered. In particular at the seventh postoperative day the frequency obtained using the objective methods was 63.3% while that obtained with subjective methods was 83%. At 1 year follow-up a frequency of sensory impairment of 12.8% was obtained using objective methods and a frequency of 18.4% when subjective methods were used. The data were analysed using the index of inter-rater reliability (Cohen's Kappa) with the degree of nerve damage evaluated by objective methods considered the "gold standard." The value of Cohen's Kappa at 1 week follow-up is 0.53; at 1 year follow-up it increased to 0.90. CONCLUSIONS: On the basis of these results, objective methods provide the most sensitive diagnostic tests at early controls within 3 months of the operation. At later control points the sensitivity increases and the inter-rater reliability is satisfactory. PMID- 17719388 TI - Ten years of descending necrotizing mediastinitis: management of 23 cases. AB - PURPOSE: Through a 10-year retrospective study, we report our experience in the management of descending necrotizing mediastinitis (DNM), a rare and often lethal complication of odontogenic and oropharyngeal infections. PATIENTS AND METHODS: We reassessed 23 patients between the ages of 16 and 69 years (mean, 49 years) seen between 1996 and 2005, with DNM secondary to odontogenic abscess or phlegmon in 9 cases or secondary to peritonsillar abscess in 14 cases. In this study, 48% of the patients had immune system disorders, mainly diabetes mellitus (6 patients). The diagnosis of DNM was confirmed by cervicothoracic computed tomography. RESULTS: Eight patients underwent a bilateral collar cervicotomy, and 15 underwent a combined cervicothoracic approach. Five, 2, 1, and 1 patients underwent surgery 2, 3, 4, and 5 times, respectively. Seven patients died as a result of septic shock and multiorgan failure, for a mortality rate of 30.4%. Four of those who died had a compromised immune system. CONCLUSION: The relatively high mortality rate seen in this study shows that, in addition to early diagnosis and aggressive treatment, it is important to give greater attention to and be more medically and surgically aggressive in the management of patients whose immune system is compromised in any way. PMID- 17719389 TI - Characterization of 3 oral squamous cell carcinoma cell lines with different invasion and/or metastatic potentials. AB - PURPOSE: Proteolytic enzymes may confer specific types of invasion and metastasis in patients with oral squamous cell carcinoma (OSCC). The purpose of this study was to determine if OSCC that invades adjacent bone has different proteolytic enzyme expression profiles than OSCC that metastasizes to lymph nodes or distant organs. Three OSCC cell lines, BHY, HSC-3, and HN, with known behavior regarding bone invasion and lymph node and distant metastatic profiles, were evaluated. The characteristics of a control, human normal nasal epithelial cell line (HNEC), and BHY, HSC-3 and HN were evaluated with regard to their expression of the matrix metalloproteinases and cathepsins. MATERIALS AND METHODS: Expressions of proteolytic enzymes including matrix metalloproteinase, MMP-1, MMP-2, MMP-3, MMP 9, extracellular matrix metalloproteinase inducer (EMMPRIN), cathepsin B, and cathepsin L were compared using immunocytochemistry and flow cytometry in 3 OSCC cell lines and HNEC. The cell morphologies of these 4 cell lines were compared using transmission electron microscopy (TEM). RESULTS: All OSCC cell lines showed higher expression of all the proteolytic proteins when compared with HNEC, except the HSC-3 cell line showed no difference in the expression of MMP-9. There was no detectable difference at the expression level of MMP-1, MMP-2, MMP-3, cathepsin B, and cathepsin L in any of the OSCC cell lines. However, MMP-9 and EMMPRIN levels were higher in the BHY cell line. According to electron microscopy, the cells of the HSC-3 cell line were the smallest and least differentiated among the 3 OSCC cell lines. The BHY cell line was the most highly differentiated showing interdigitation and numerous cell junctions. CONCLUSIONS: MMPs play an important role in the invasion and metastasis of oral cancer. MMP-9 might play a more important role than MMP-2 during invasion. Increased expression of MMP-1, MMP-9, and EMMPRIN proteins might be involved in invasion of OSCC to adjacent bone, as they are necessary for the collagen matrix degradation. Increased expression of MMP-3, cathepsin B and L in OSCC might be associated with both invasion and a high incidence of metastasis. PMID- 17719390 TI - Evaluation of autologous platelet-poor plasma gel as a hemostatic adjunct after posterior iliac crest bone harvest. AB - PURPOSE: To evaluate the hemostatic efficacy of autologous platelet-poor plasma (PPP) gel following posterior iliac crest bone graft harvesting for oral and maxillofacial reconstruction. PATIENTS AND METHODS: This was a prospective study of 24 consecutive patients involving 26 posterior iliac crest bone harvests that had bone wax and either 1-gram of bovine microfibrillar collagen or 20 mL of autologous PPP, activated as a gel, used as adjunct hemostatic agents. Compression bulb suction drain was placed into the graft site and drain output recorded every 8 hours for 64 hours. Cost analysis was also undertaken between the 2 methods. Statistical significance between means of each group was determined by Student's t test and found significant for P < .05. RESULTS: There were no statistically significant differences in average drain output between the PPP and MFC groups for each 8-hour interval. There was no statically significant difference in average total drain output between the PPP and MFC groups over the entire 64 hour period. Additionally, unlike the addition of MFC, the addition of PPP added no additional costs to the procedure. CONCLUSION: PPP gel, when compared with bovine microfibrillar collagen, is an effective and inexpensive adjunct in hemostasis following posterior iliac crest bone harvest. PMID- 17719391 TI - The oral and systemic impact of third molar periodontal pathology. AB - PURPOSE: Analyze in pregnant subjects the relationship between third molar periodontal pathology, and subjects' overall periodontal status. Assess also, the associations between postpartum periodontal status by jaw and a systemic impact, preterm birth, or elevated serum C-reactive protein (CRP). PATIENTS AND METHODS: Data were from an IRB-approved study, Oral Conditions and Pregnancy. In this clinical study, full-mouth periodontal examinations including third molars were conducted at greater than 24 weeks of pregnancy and again within 72 hours of delivery. For our analyses, mean periodontal probing depth (PD) by visible tooth and by jaw were calculated at enrollment and postpartum. Subjects were categorized by 3 broad levels of periodontal health, considered the primary outcome variable. The primary predictor variable for levels of periodontal health was the presence or absence of visible third molars. Mean periodontal probing depth in the mandible or maxilla at term was considered an indicator of a possible risk of systemic exposure, increasing the odds of preterm birth, less than 37 weeks gestation, or elevated serum CRP levels. Chi-square and t tests were used to determine statistical significance, .05. Significant predictor variables were included in multivariable models. Unconditional logistic multivariate models were used to derive odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Data from examinations at enrollment and postpartum were available for 1,020 and 891 subjects, respectively. Visible third molars were detected in 405 subjects at enrollment and in 360 subjects at term. No subjects had third molars removed during the study. At enrollment and postpartum, subjects with visible third molars were significantly more likely to have moderate/severe periodontal disease, 23.5% versus 8.5%, and 18.3 versus 9.4%, respectively. Mean PD was significantly greater for maxillary and mandibular molars than for more anterior teeth, P < .01. In both jaws, mean PD tended to be progressively greater from first to third molars. No differences were found in mean PD by jaw. In subjects with visible third molars, adjusting for the severity of mandibular periodontal disease, the level of maxillary periodontal disease was significantly associated with preterm birth, P < .01, OR 2.6 (95% CI 1.1-6.8), or the upper quartile of serum CRP at term, at least 23.0 mg/L postpartum, P = .05, OR 2.5 (95% CI 1.2-5.1). CONCLUSIONS: Subjects' detected levels of periodontal disease were greater at enrollment and postpartum if visible third molars were detected. PMID- 17719392 TI - Application of intermaxillary fixation screws in maxillofacial trauma. AB - PURPOSE: The use of intermaxillary fixation (IMF) in the treatment of maxillofacial trauma represents the cornerstone of fracture reduction and immobilization. Many modalities of IMF have been described; recently IMF screws have been introduced into clinical practice, however, hardware failure can occur. We performed a retrospective study evaluating hardware-associated complications for self-drilling/tapping IMF screws. MATERIALS AND METHODS: A retrospective study on 49 patients requiring IMF was performed. The diagnosis, duration of IMF, screw site, use of elastic or wire fixation, and associated complications were recorded. IMF screws were used to adjunct open reduction techniques, for definitive closed reduction, or fracture prevention following dentoalveolar surgery. Follow-up examinations were performed until fracture healing was complete (6 to 8 weeks). RESULTS: A single adverse event occurred in 19 patients (39%) while 4 patients (8%) had more than 1 complication. The most common event was screw loosening; 29% of patients had at least 1 screw dislodged in the treatment period. Of the total number of screws placed (229), 15 (6.5%) became loose, and were equally distributed among the mandible and maxilla. The remaining complications noted were root fracture, 4% (2 of 49); loosened wires, 6% (3 of 49); screw shear, 2% (1 of 49); malocclusion, 2% (1 of 49); and ingested hardware, 2% (1 of 49). CONCLUSIONS: Overall the IMF self-drilling/tapping screws have been shown to be a useful modality to establish maxillomandibular fixation. It is a safe, and time-sparing technique; however, it is not without limitations or potential consequences which the surgeon must be aware of in order to provide safe and effective treatment. PMID- 17719393 TI - Endoscopic intraoral plating of orbital floor fractures. AB - PURPOSE: This article describes a new endoscopic approach for orbital floor fractures, reduction, and fixation and reports the clinical results. PATIENTS AND METHODS: Ten patients who sustained either a comminuted or trap door orbital floor fracture were treated in 2 medical centers following the same surgical protocol. The indications for orbital reconstruction were limited eye movement, diplopia, and significant enophthalmos. The new approach is discussed in detail. RESULTS: All patients healed uneventfully. No major complications were noted in the postoperative period, and good functional and esthetic results were obtained. CONCLUSIONS: Our results demonstrate that endoscopic intraoral plating is a safe and effective procedure for treating orbital floor fractures. PMID- 17719394 TI - Use of straight and curved 3-dimensional titanium miniplates for fracture fixation at the mandibular angle. AB - PURPOSE: The aim of this follow-up study was to evaluate the clinical usefulness of a new type of 3-dimensional (3D) miniplate for open reduction and monocortical fixation of mandibular angle fractures. PATIENTS AND METHODS: In 20 consecutive patients, noncomminuted mandibular angle fractures were treated with open reduction and fixation using a 2 mm 3D miniplate system in a transoral approach. All patients were systematically monitored until 6 months postoperatively. Among the outcome parameters recorded were infection, hardware failure, wound dehiscence, and sensory disturbance of the inferior alveolar nerve. RESULTS: The mean operation time from incision to wound closure was 65 minutes. Two patients had a mucosal wound dehiscence with no consequences. None developed an infection requiring a plate removal. All but 2 patients had normal sensory function 3 months after surgery. Plate fracture occurred in one patient in whom a preceding surgical removal of the third molar had been the reason for the mandibular fracture. In the absence of clinical symptoms, the patient declined plate removal. On final follow-up, fracture healing was considered clinically complete in all patients. CONCLUSIONS: The 3D plating system described here is suitable for fixation of simple mandibular angle fractures and is an easy-to-use alternative to conventional miniplates. The system may be contraindicated in patients in whom insufficient interfragmentary bone contact causes minor stability of the fracture. PMID- 17719395 TI - The value of a diagnostic setup for full fixed maxillary implant prosthetics. AB - The concept of prosthesis-directed implant-supported restoration is well accepted. The implementation of this principle for patients requesting full fixed implant-supported maxillary prosthetics has not been thoroughly described. We present a technique for the evaluation and preprosthetic surgical management of patients who are edentulous in the maxilla and wish to have fixed implant supported crown and bridge prosthetics. PMID- 17719397 TI - Use of a resorbable nut system for simultaneous implant insertion and maxillary sinus floor elevation. PMID- 17719396 TI - Measurement of anterior loop length for the mandibular canal and diameter of the mandibular incisive canal to avoid nerve damage when installing endosseous implants in the interforaminal region. AB - PURPOSE: To measure the anterior loop length (ALL) for the mandibular canal and diameter of the mandibular incisive canal at various points to ascertain the mesial distance from the mental foramen at which it is safe to install endosseous implants in the most distal area of the interforaminal region. PATIENTS AND METHODS: Using 38 cadavers (75 hemimandibles), the ALL and the diameter of the incisive canal at its origin and at 1 mm intervals up to 5 mm mesially from the origin were measured using operative calipers. RESULTS: Measured data are expressed as minimum, maximum, and mean +/- standard deviation. ALL was 0.0, 6.0, and 1.5 +/- 1.4 mm, the diameter of the incisive canal was 1.0, 6.6, and 3.1 +/- 1.2 mm at the origin, 0.6, 5.8, and 2.6 +/- 1.1 mm at 1 mm, 0.5, 5.7, and 2.2 +/- 1.0 mm at 2 mm, 0.5, 6.0, and 2.0 +/- 1.0 mm at 3 mm, 0.5, 5.0, and 1.8 +/- 0.8 mm at 4 mm, and 0.5, 4.9, and 1.7 +/- 0.8 mm at 5 mm mesially. CONCLUSION: The above results showed that because there may be large variations in the ALL and the diameter of the incisive canal, one should not assume that a fixed distance mesially from the mental foramen will be safe. Intraoperative examination of vital structures is indispensable for the safe installation of implants in the interforaminal area of the mandible. Not only the ALL but also the diameter of the incisive canal should be investigated on a case-by-case basis to determine the appropriate location for each individual. PMID- 17719398 TI - Novel use of nasal suction during the maxillary sinus lift procedure. PMID- 17719399 TI - Cutaneous cryotherapy in maxillofacial surgery. PMID- 17719400 TI - Prevention of wrong-site tooth extraction: clinical guidelines. AB - Wrong-site tooth extraction can be defined as the extraction of a tooth other than the one intended by the referring dentist. This adverse event continues to be one of the major reasons for filing malpractice claims against oral and maxillofacial surgeons. Most cases of wrong-site tooth extractions are preventable and can be minimized by the development of an educational program, an informative, unambiguous referral form, a pre-operative check list, and incorporation of the Universal Protocol for Preventing Wrong Site, Wrong Procedure, Wrong Person Surgery into daily clinical practice. PMID- 17719401 TI - Ameloblastic carcinoma (primary type) isolated to the anterior maxilla: case report with review of the literature. PMID- 17719402 TI - Modified sagittal split ramus osteotomy for malpositioned mandibular foramina with prognathia. PMID- 17719403 TI - Pseudoaneurysm of a branch of the maxillary artery following mandibular sagittal split ramus osteotomy: case report and review of the literature. PMID- 17719404 TI - Dentinogenic ghost cell tumors. PMID- 17719405 TI - Odontogenic ghost cell carcinoma in the maxilla: a case report and literature review. PMID- 17719406 TI - Surgical management of maxillofacial uremic osteodystrophy: a case report. PMID- 17719408 TI - Giant benign chondroid syringoma of the cheek: case report and review of the literature. PMID- 17719407 TI - Rare benign tumors of the mandibular condyle: report of 2 cases and literature review. PMID- 17719409 TI - Modified osteotome for inferior border sagittal split osteotomy. PMID- 17719410 TI - New protocol for 1-stage treatment of temporomandibular joint ankylosis using surgical navigation. PMID- 17719411 TI - Use of a transbuccal technique for marginal mandibulectomy: a novel approach. PMID- 17719412 TI - Vector guidance splint for internal maxillary distraction. PMID- 17719413 TI - Open tracheotomy using a novel device. PMID- 17719414 TI - Biodegradable screw fixation in maxillofacial distraction osteogenesis. PMID- 17719415 TI - Transport distraction osteogenesis of a dentoalveolar segment in the posterior mandible: a technical note. PMID- 17719416 TI - Arterial stents for access and protection of the parotid and submandibular ducts during sialoendoscopy. PMID- 17719417 TI - Composite skin-muscle-mucosal flap based on the superior labial artery for lower lip reconstruction. PMID- 17719418 TI - An easy method for predictable osteotomies in the vascularized fibula flap for mandibular reconstruction. PMID- 17719419 TI - Modification of the anterior mandibular osteotomy for genioglossus advancement with hyoid suspension for obstructive sleep apnea. PMID- 17719420 TI - X-ray-based volumetric imaging of foreign bodies: a comparison of computed tomography and digital volume tomography. PMID- 17719421 TI - Obstructive parotid ductal disease: intraoral management. PMID- 17719422 TI - Human patient simulator for training oral and maxillofacial surgery residents in general anesthesia and airway management. PMID- 17719423 TI - Staging bisphosphonate-related osteonecrosis of the jaw should include early stages of disease. PMID- 17719424 TI - Implant surgery and a plunging ranula. PMID- 17719425 TI - ? PMID- 17719426 TI - ? PMID- 17719427 TI - ? PMID- 17719428 TI - ? PMID- 17719429 TI - ? PMID- 17719430 TI - ? PMID- 17719431 TI - ? PMID- 17719433 TI - ? PMID- 17719432 TI - ? PMID- 17719467 TI - Surgical myectomy versus alcohol septal ablation for obstructive hypertrophic cardiomyopathy. Will there ever be a randomized trial? AB - Dynamic left ventricular outflow tract obstruction is an important pathophysiologic feature of hypertrophic cardiomyopathy (HCM) and a predictor of clinical deterioration and cardiovascular mortality. Patients with marked obstruction and severe limiting symptoms refractory to maximum medical management are considered candidates for invasive septal reduction therapy, which includes surgical myectomy and alcohol septal ablation (ASA). Availability of both surgical myectomy and ASA has polarized the cardiovascular community concerning the most appropriate implementation of these two interventions. The ensuing controversy of whether myectomy and ASA are truly equivalent options has resulted in calls for a prospective randomized trial. However, upon analysis, such a myectomy versus ASA trial, adequately powered to compare the key issue of long term outcome, poses a myriad of practical problems that seem virtually insurmountable. Therefore, it is appropriate to revisit this evolving debate at this time, identify the unique obstacles to a randomized study design, and achieve some clarity concerning the most realistic clinical strategies for symptomatic patients with HCM and outflow obstruction. PMID- 17719466 TI - Resting heart rate in cardiovascular disease. AB - The importance of resting heart rate (HR) as a prognostic factor and potential therapeutic target is not yet generally accepted. Recent large epidemiologic studies have confirmed earlier studies that showed resting HR to be an independent predictor of cardiovascular and all-cause mortality in men and women with and without diagnosed cardiovascular disease. Clinical trial data suggest that HR reduction itself is an important mechanism of benefit of beta-blockers and other heart-rate lowering drugs used after acute myocardial infarction, in chronic heart failure, and in stable angina pectoris. Pathophysiological studies indicate that a relatively high HR has direct detrimental effects on the progression of coronary atherosclerosis, on the occurrence of myocardial ischemia and ventricular arrhythmias, and on left ventricular function. Studies have found a continuous increase in risk with HR above 60 beats/min. Although it may be difficult to define an optimal HR for a given individual, it seems desirable to maintain resting HR substantially below the traditionally defined tachycardia threshold of 90 or 100 beats/min. These findings suggest that the potential role of HR and its modulation should be considered in future cardiovascular guidance documents. PMID- 17719468 TI - Beneficial effects of valsartan in asymptomatic individuals with vascular or cardiac abnormalities: the DETECTIV Pilot Study. AB - OBJECTIVES: We studied the efficacy of valsartan (Val) to slow cardiovascular disease progression in asymptomatic high-risk prehypertensive or hypertensive patients with blood pressure (BP) controlled to <140/90 mm Hg and with evidence for functional or structural alterations in the cardiovascular system. BACKGROUND: Identifying individuals with early markers for cardiovascular disease raises the possibility for pharmacotherapy to slow progression and delay or prevent future morbid events. METHODS: Seventy-six subjects with a Rasmussen Disease Score (RDS) of 6 or higher were randomized double-blind to receive placebo (Plac) or Val 160 mg once daily for 6 months followed by 6 months of single-blind Val in both groups. A panel of 10 tests, including large and small artery elasticity, resting and treadmill exercise BP, carotid intimal-media thickness, retinal vascular photography, micro-albuminuria, electrocardiography, echocardiography, and plasma B-type natriuretic peptide, was performed at baseline and after 6 and 12 months of treatment. Each test result was scored as normal (0), borderline (1), or abnormal (2), and the total RDS was calculated by adding all the scores of the individual tests. RESULTS: Valsartan significantly reduced the RDS after 6 months versus Plac (p < 0.03) and at 12 months (either 12 or 6 months of Val, p < 0.0001). The major contribution in risk score reduction was due to an increase in small artery elasticity and a decrease in BP, and after 12 months there was a reduction in left ventricular mass index (p < 0.03). CONCLUSIONS: Valsartan can slow progression and/or reverse early cardiovascular disease in asymptomatic high-risk patients with prehypertension or BP controlled to <140/90 mm Hg. PMID- 17719469 TI - Hypertension in the young: preventing the evolution of disease versus prevention of clinical events. PMID- 17719470 TI - Metabolic syndrome increases operative mortality in patients undergoing coronary artery bypass grafting surgery. AB - OBJECTIVES: The aim of this study was to determine the impact of the metabolic syndrome (MS) on operative mortality after a coronary artery bypass grafting surgery (CABG). BACKGROUND: Diabetes and obesity are highly prevalent among patients undergoing CABG. However, it remains unclear whether these factors have a significant impact on operative mortality after this procedure. We hypothesized that the metabolic abnormalities associated with MS could negatively influence the operative outcome of CABG surgery. METHODS: We retrospectively analyzed the data of 5,304 consecutive patients who underwent an isolated CABG procedure between 2000 and 2004. Of these 5,304 patients, 2,411 (46%) patients met the National Cholesterol Education Program-Adult Treatment Panel III criteria for MS. The primary end point was operative mortality. RESULTS: The operative mortality after CABG surgery was 2.4% in patients with MS and 0.9% in patients without MS (p < 0.0001). The MS was a strong independent predictor of operative mortality (relative risk 3.04 [95% confidence interval (CI) 1.73 to 5.32], p = 0.0001). After adjusting for other risk factors, the risk of mortality was increased 2.69 fold (95% CI 1.43 to 5.06; p = 0.002) in patients with MS and diabetes and 2.36 fold (95% CI 1.26 to 4.41; p = 0.007) in patients with MS and no diabetes, whereas it was not significantly increased in the patients with diabetes and no MS. CONCLUSIONS: This is the first study to report that MS is a highly prevalent and powerful risk factor for operative mortality in patients undergoing a CABG surgery. Thus, interventions that could contribute to reduce the prevalence of MS in patients with coronary artery disease or that could acutely modify the metabolic perturbations of MS at the time of CABG might substantially improve survival in these patients. PMID- 17719471 TI - Ezetimibe and simvastatin reduce inflammation, disease activity, and aortic stiffness and improve endothelial function in rheumatoid arthritis. AB - OBJECTIVES: The aim of this study was to investigate the effect of simvastatin and ezetimibe on inflammation, disease activity, endothelial dysfunction, and arterial stiffness in a cohort of rheumatoid arthritis (RA) patients. BACKGROUND: Rheumatoid arthritis is a chronic inflammatory condition associated with increased cardiovascular risk. Statins reduce inflammation and disease activity in RA patients, but whether this is due to pleiotropism or cholesterol lowering per se is unclear. METHODS: Twenty patients received 20 mg simvastatin or 10 mg ezetimibe each for 6 weeks in a randomized double-blind crossover study. Disease activity, blood pressure, aortic pulse wave velocity (PWV), brachial artery flow mediated dilation (FMD), and serum inflammatory markers were measured before and after each treatment. RESULTS: Both ezetimibe and simvastatin significantly reduced total cholesterol (-0.62 +/- 0.55 mmol/l and -1.28 +/- 0.49 mmol/l, respectively; p < 0.001), low-density lipoprotein cholesterol (-0.55 +/- 0.55 mmol/l and -1.28 +/- 0.49 mmol/l; p < 0.0001), and C-reactive protein (-5.35 +/- 9.25 mg/l and -5.05 +/- 6.30 mg/l; p < 0.001). Concomitantly, Disease Activity Score (-0.55 +/- 1.01 and -0.67 +/- 0.91; p = 0.002), aortic PWV (-0.69 +/- 1.15 m/s and -0.71 +/- 0.71 m/s; p = 0.001), and FMD (1.37 +/- 1.17% and 2.51 +/- 2.13%; p = 0.001) were significantly improved by both drugs. CONCLUSIONS: This study demonstrates that both ezetimibe and simvastatin reduce disease activity and inflammatory markers to a similar extent in patients with RA. Therapy is also associated with a concomitant reduction in aortic PWV and improvement in endothelial function. This suggests that cholesterol lowering per se has anti inflammatory effects and improves vascular function in RA. PMID- 17719472 TI - Identification of a potential cardiac antifibrotic mechanism of torasemide in patients with chronic heart failure. AB - OBJECTIVES: This study sought to investigate whether torasemide inhibits the enzyme involved in the myocardial extracellular generation of collagen type I molecules (i.e., procollagen type I carboxy-terminal proteinase [PCP]). BACKGROUND: Torasemide has been reported to reduce myocardial fibrosis in patients with chronic heart failure (HF). METHODS: Chronic HF patients received either 10 to 20 mg/day oral torasemide (n = 11) or 20 to 40 mg/day oral furosemide (n = 11) in addition to their standard HF therapy. At baseline and after 8 months from randomization, right septal endomyocardial biopsies were obtained to analyze the expression of PCP by Western blot and the deposition of collagen fibers (collagen volume fraction [CVF]) with an automated image analysis system. The carboxy-terminal propeptide of procollagen type I (PICP) released as a result of the action of PCP on procollagen type I was measured in serum by radioimmunoassay. RESULTS: The ratio of PCP active form to PCP zymogen, an index of PCP activation, decreased (p < 0.05) in torasemide-treated patients and remained unchanged in furosemide-treated patients. A reduction (p < 0.01) in both CVF and PICP was observed in torasemide-treated but not in furosemide-treated patients. Changes in PCP activation were positively correlated (p < 0.001) with changes in CVF and changes in PICP in patients receiving torasemide. CONCLUSIONS: These findings suggest the hypothesis that the ability of torasemide to reduce myocardial fibrosis in chronic HF patients is related to a decreased PCP activation. Further studies are required to ascertain whether PCP may represent a new target for antifibrotic strategies in chronic HF. PMID- 17719473 TI - Remote magnetic navigation: human experience in pulmonary vein ablation. AB - OBJECTIVES: We aimed at assessing the feasibility and efficacy of remote magnetic navigation (MN) and ablation in patients with atrial fibrillation (AF). BACKGROUND: This novel MN system could facilitate standardization of the procedures, reducing the importance of the operator skill. METHODS: After becoming familiar with the system in 48 previous patients, 45 consecutive patients with AF were considered for ablation using the Niobe II remote magnetic system (Stereotaxis, St. Louis, Missouri) in a stepwise approach: circumferential pulmonary vein ablation (CPVA), pulmonary vein antrum isolation (PVAI), and, if failed, PVAI using the conventional approach. Remote navigation was done using the coordinate or the wand approach. Ablation end point was electrical disconnection of the pulmonary veins (PVs). RESULTS: Using the coordinate approach, the target location was reached in only 60% of the sites, whereas by using the wand approach 100% of the sites could be reached. After step 2 ablation, only 1 PV in 4 patients (8%) could be electrically isolated. Charring on the ablation catheter tip was seen in 15 (33%) of the cases. In 23 patients, all PVs were isolated with the conventional thermocool catheter, and in 22 patients only the right PVs were isolated with the conventional catheter. After a mean follow-up period of 11 +/- 2 months, recurrence was seen in 5 patients (22%) with complete PVAI and in 20 patients (90%) with incomplete PVAI. CONCLUSIONS: Remote navigation using a magnetic system is a feasible technique. With the present catheter technology, effective lesions cannot be achieved in most cases. This appears to impact the cure rate of AF patients. PMID- 17719474 TI - Is pulmonary vein antrum isolation a critical determinant of recurrent arrhythmias after ablation of atrial fibrillation? PMID- 17719475 TI - First human demonstration of cardiac stimulation with transcutaneous ultrasound energy delivery: implications for wireless pacing with implantable devices. AB - OBJECTIVES: The purpose of this study was to evaluate the feasibility and safety of a novel technology that uses energy transfer from an ultrasound transmitter to achieve cardiac stimulation without the use of a pacing lead in humans. BACKGROUND: To overcome the limitations of pacemaker leads, a new technology enabling stimulation without the use of a lead is desirable. METHODS: A steerable bipolar electrophysiology catheter incorporating a receiver electrode into the tip and circuitry to convert ultrasound energy to electrical energy was inserted transvenously into the heart. An ultrasound transmitting transducer was placed on the chest wall with ultrasound gel. Ultrasound energy was amplitude-adjusted and transmitted at 313 to 385 kHz. The output waveform of the receiver electrode was monitored while the transmitter was moved on the chest wall to target the receiver. The ultrasound transmission amplitude was limited to a mechanical index of 1.9, the maximum allowed for ultrasound imaging systems. Ultrasound-mediated pacing with minimum voltage but consistent capture was obtained for 12 s. RESULTS: Twenty-four patients (48 +/- 12 years) were tested during or after completion of clinical electrophysiology procedures. A total of 80 pacing sites were tested (mean 3.3 sites/patient): 12 right atrial, 35 right ventricular, and 33 left ventricular (31 endocardial) sites. The transmit-to-receive distance was 11.3 +/- 3.2 cm (range 5.3 to 22.5 cm). Ultrasound-mediated pacing was achieved at all 80 test sites, with consistent capture at 77 sites. The mechanical index during pacing was 0.5 +/- 0.3 (range 0.1 to 1.5). The mean ultrasound-mediated capture threshold was 1.01 +/- 0.64 V. There was no adverse event related to ultrasound pacing. No patient experienced discomfort during pacing. CONCLUSIONS: The feasibility and safety of pacing usng ultrasound energy has been shown acutely. PMID- 17719476 TI - Preferential conduction across the ventricular outflow septum in ventricular arrhythmias originating from the aortic sinus cusp. AB - OBJECTIVES: The purpose of this study was to examine the relationship between the origin and breakout site of idiopathic ventricular tachycardia (VT) or premature ventricular contractions (PVCs) originating from the myocardium around the ventricular outflow tract. BACKGROUND: The myocardial network around the ventricular outflow tract is not well known. METHODS: We studied 70 patients with idiopathic VT (n = 23) or PVCs (n = 47) with a left bundle branch block and inferior QRS axis morphology. Electroanatomical mapping was performed in both the right ventricular outflow tract (RVOT) and aortic sinus cusp (ASC) during VT or PVCs. RESULTS: The earliest ventricular activation (EVA) was recorded in the RVOT in 55 patients (group R) and in the ASC in 15 (group A). In all group R patients, the closest pace map and successful ablation were achieved at the EVA site. Although a successful ablation was achieved at the EVA site in all group A patients, the closest pace map was obtained at the EVA site in 8 and RVOT in 7 (with an excellent pace map in 4). The stimulus to QRS interval was 0 ms during pacing from the RVOT and 36 +/- 8 ms from the ASC. The distance between the EVA and perfect pace map sites in those 4 patients was 11.9 +/- 3.0 mm. CONCLUSIONS: Ventricular arrhythmias originating from the ASC often show preferential conduction to the RVOT, which may render pace mapping or some algorithms using the electrocardiographic characteristics less reliable. In some of those cases, an insulated myocardial fiber across the ventricular outflow septum may exist. PMID- 17719477 TI - (18)Fluorodeoxyglucose positron emission tomography imaging of atherosclerotic plaque inflammation is highly reproducible: implications for atherosclerosis therapy trials. AB - OBJECTIVES: This study tested the near-term reproducibility of (18)fluorodeoxyglucose positron emission tomography (FDG-PET) imaging of atherosclerosis. BACKGROUND: It is known that FDG-PET can measure inflammation within the aorta, carotid, and vertebral arteries with histologic validation in humans and animal models of disease. By tracking changes in inflammation over time, PET could be used as a surrogate marker of antiatheroma drug efficacy. However, the short-term variability and reproducibility of the technique are unknown. METHODS: We imaged the carotid arteries and aorta in 11 subjects with FDG-PET/computed tomography twice, 14 days apart. We assessed interobserver and intraobserver agreement and interscan variability. RESULTS: Interscan plaque FDG variability over 2 weeks was very low; intraclass correlation coefficients (ICC) ranged between 0.79 and 0.92. Interobserver agreement was high across all territories imaged except aortic arch (ICC values from 0.90 to 0.97, arch 0.71). Intraobserver agreement was high, with ICC values between 0.93 and 0.98. CONCLUSIONS: Spontaneous change in plaque FDG uptake is low over 2 weeks, with favorable inter- and intraobserver agreement. Power calculations suggest that drug studies using FDG-PET imaging would require few subjects compared with other imaging modalities. This study strengthens the case for FDG-PET as a noninvasive plaque imaging technique. PMID- 17719479 TI - High-septal pacing reduces ventricular electrical remodeling and proarrhythmia in chronic atrioventricular block dogs. AB - OBJECTIVES: This study was designed to analyze the relevance of ventricular activation patterns for ventricular electrical remodeling after atrioventricular (AV) block in dogs. BACKGROUND: Bradycardia is thought to be the main contributor to ventricular electrical remodeling after complete AV block. However, an altered ventricular activation pattern or AV dyssynchrony may also contribute. METHODS: For 4 weeks, AV block dogs were either paced from the high-ventricular septum near the His bundle at lowest captured rate (n = 9, high-septal pacing [HSP]) or kept at idioventricular rate without controlled activation (n = 14, chronic AV block [CAVB]). Multiple electrocardiographic and electrophysiological parameters were measured under anesthesia at 0 and 4 weeks. Proarrhythmia was tested at 4 weeks by I(Kr) block (25 mug/kg dofetilide intravenous). RESULTS: At 0 weeks, the 2 groups were comparable, whereas after 4 weeks of similar bradycardia, QT duration at unpaced conditions had increased from 300 +/- 5 to 395 +/- 18 ms in CAVB (+32 +/- 6%) and from 307 +/- 8 ms to 357 +/- 11 ms in HSP (+17 +/- 4%; p < 0.05). Frequency dependency of repolarization was less steep in HSP compared to CAVB dogs after 4 weeks remodeling. Beat-to-beat variability of repolarization, a proarrhythmic parameter, increased only in CAVB from 0 to 4 weeks. Torsades de pointes arrhythmias were induced at 4 weeks in 44% HSP versus 78% CAVB dogs (p = 0.17). Cumulative duration of arrhythmias per inducible dog was 87 +/- 36 s in CAVB and 30 +/- 21 s in HSP (p < 0.05). CONCLUSIONS: High-septal pacing reduces the magnitude of ventricular electrical remodeling and proarrhythmia in AV block dogs, suggesting a larger role for altered ventricular activation pattern in the generation of ventricular electrical remodeling than previously assumed. PMID- 17719478 TI - Elevated levels of inflammation, d-dimer, and homocysteine are associated with adverse calf muscle characteristics and reduced calf strength in peripheral arterial disease. AB - OBJECTIVES: This study determined whether increased levels of inflammatory blood markers, D-dimer, and homocysteine were associated with smaller calf skeletal muscle area, increased calf muscle percent fat, reduced calf muscle density, and poorer calf strength in persons with lower extremity peripheral arterial disease (PAD). BACKGROUND: Elevated levels of inflammatory markers and D-dimer are associated with greater functional impairment and functional decline in persons with PAD. Mechanisms of these associations are unknown. METHODS: Participants were 423 persons with PAD. Calf muscle area, percent fat, and density were measured with computed tomography. Physical activity levels were measured objectively over 7 days with the Caltrac (Muscle Dynamics Fitness Network, Inc., Rocklin, California) vertical accelerometer. Isometric plantarflexion strength was measured. Analyses were adjusted for age, gender, race, comorbidities, the ankle-brachial index, and other potential confounders. RESULTS: Higher levels of D-dimer (p = 0.014), C-reactive protein (CRP) (p = 0.002), interleukin (IL)-6 (p < 0.001), and soluble vascular cellular adhesion molecule (sVCAM)-1 (p = 0.008) were associated with smaller calf muscle area. Higher sVCAM-1 (p = 0.004) and IL 6 (p = 0.017) were associated with higher calf muscle percent fat. Higher D-dimer (p < 0.001), sVCAM-1 (p < 0.001), and homocysteine (p = 0.014) were associated with lower calf muscle density. These associations were generally unchanged after additional adjustment for physical activity. Higher sVCAM-1 (p = 0.013) was associated with lower calf strength. CONCLUSIONS: These data show, for the first time, that higher levels of inflammation, D-dimer, and homocysteine are associated with more adverse calf muscle characteristics in persons with PAD. These associations may contribute to previously established associations between elevated biomarkers and functional impairment and functional decline in PAD. PMID- 17719480 TI - WATCHMAN for stroke prevention: an out-of-date procedure. PMID- 17719483 TI - Deadly dengue: new vaccines promise to tackle this escalating global menace. PMID- 17719482 TI - Regional differences in African Americans' high risk for stroke: the remarkable burden of stroke for Southern African Americans. AB - PURPOSE: The stroke mortality rate for African Americans aged 45 to 64 years is 3 to 4 times higher than for whites of the same age, with a decreasing black-to white mortality ratio with increasing age. There is also a "STROKE BELT" with higher stroke mortality in the southeastern United States. This study assesses if there are also geographic variations in the magnitude of the excess stroke mortality for African Americans. METHODS: The age- and sex-specific black-to white mortality ratio was calculated for each of 26 states with a sufficient African American population for stable estimates. The southern excess was calculated as the percentage excess of southern over nonsouthern rates. RESULTS: Across age and sex strata, the black-to-white stroke mortality ratio was consistently higher for southern states, with an average black-to-white stroke mortality ratio that ranged from 6% to 21% higher among southern states than in nonsouthern states. CONCLUSIONS: The increase in stroke mortality rates for African Americans in southern states is even larger than expected. That southern states that are not part of the "STROKE BELT" (Virginia and Florida) also have an elevated black-to-white mortality ratio suggests the mechanism of higher risk for African Americans may be independent of the causes contributing to "STROKE BELT." PMID- 17719484 TI - Cooperativity in glycan-protein interactions. AB - Using FGF-2 HSGAGs as a model, de Paz and colleagues [1] have demonstrated the importance of multivalency in cooperative glycan-protein interactions to achieve specificity. PMID- 17719485 TI - Foundations for directed alkaloid biosynthesis. AB - In this issue of Chemistry & Biology, Bernhardt and coworkers [1] assay the functional plasticity of strictosidine synthase, a gateway enzyme in the biosynthetic pathways of monoterpene indole alklaloids, and the downstream operability of the products of strictosidine synthase variants in the larger context of the plant biosynthetic pathways. PMID- 17719486 TI - Site-specific oxidative stress induction. AB - In this issue of Chemistry & Biology, Kelly and colleagues describe the development of two novel ROS-generating compounds [1] that specifically localize in the nucleus or mitochondrion. Their application reveals that nuclei and mitochondria respond differently to oxidative stress, in terms of gene expression and survival pathway activation. PMID- 17719487 TI - Potentiation of fibroblast growth factor activity by synthetic heparin oligosaccharide glycodendrimers. AB - Heparin is a highly sulfated polysaccharide that regulates a variety of cellular processes by interaction with a host of proteins. We report the preparation of synthetic heparin oligosaccharide glycodendrimers and their use as heparin mimetics to regulate heparin-protein interactions. The multivalent display of sugar epitopes mimics the naturally occurring glycans found on cell surfaces and enhances their binding capacity. Binding of the heparin dendrimers to basic fibroblast growth factor (FGF-2) was analyzed using heparin microarray experiments and surface plasmon resonance measurements on gold chips. Heparin coated dendrimers bind FGF-2 significantly more effectively than monovalent heparin oligosaccharides. Dendrimer 1, which displays multiple copies of the sulfated hexasaccharide (GlcNSO(3)[6-OSO(3)]-IdoA[2-OSO(3)])3, was employed to promote FGF-2-mediated mitogen-activated kinase activation, demonstrating the utility of glycodendrimers to modulate heparin-protein interactions. PMID- 17719488 TI - Rapid identification of enzyme variants for reengineered alkaloid biosynthesis in periwinkle. AB - Monoterpene indole alkaloids from Catharanthus roseus (Madagascar periwinkle), such as the anticancer agents vinblastine and vincristine, have important pharmacological activities. Metabolic engineering of alkaloid biosynthesis can provide an efficient and environmentally friendly route to analogs of these synthetically challenging and pharmaceutically valuable natural products. However, the narrow substrate scope of strictosidine synthase, the enzyme at the entry point of the pathway, limits a pathway engineering approach. We demonstrate that with a different expression system and screening method it is possible to rapidly identify strictosidine synthase variants that accept tryptamine analogs not turned over by the wild-type enzyme. The variants are used in stereoselective synthesis of beta-carboline analogs and are assessed for biosynthetic competence within the terpene indole alkaloid pathway. These results present an opportunity to explore metabolic engineering of "unnatural" product production in the plant periwinkle. PMID- 17719489 TI - A tylosin ketoreductase reveals how chirality is determined in polyketides. AB - Because it controls the majority of polyketide stereocenters, the ketoreductase (KR) is a central target in engineering polyketide synthases (PKSs). To elucidate the mechanisms of stereocontrol, the structure of KR from the first module of the tylosin PKS was determined. A comparison with a recently solved erythromycin KR that operates on the same substrate explains why their products have opposite alpha-substituent chiralities. The structure reveals how polyketides are guided into the active site by key residues in different KR types. There are four types of reductase-competent KRs, each capable of fixing a unique combination of alpha substituent and beta-hydroxyl group chiralities, as well as two types of reductase-incompetent KRs that control alpha-substituent chirality alone. A protocol to assign how a module will enforce substituent chirality based on its sequence is presented. PMID- 17719490 TI - Structural engineering of pMHC reagents for T cell vaccines and diagnostics. AB - MHC class I peptide complexes (pMHC) are routinely used to enumerate T cell populations and are currently being evaluated as vaccines to tumors and specific pathogens. Herein, we describe the structures of three generations of single chain pMHC progressively designed for the optimal presentation of covalently associated epitopes. Our ultimate design employs a versatile disulfide trap between an invariant MHC residue and a short C-terminal peptide extension. This general strategy is nondisruptive of native pMHC conformation and T cell receptor engagement. Indeed, cell-surface-expressed MHC complexes with disulfide-trapped epitopes are refractory to peptide exchange, suggesting they will make safe and effective vaccines. Furthermore, we find that disulfide-trap stabilized, recombinant pMHC reagents reliably detect polyclonal CD8 T cell populations as proficiently as conventional reagents and are thus well suited to monitor or modulate immune responses during pathogenesis. PMID- 17719491 TI - Deconvolution of the cellular oxidative stress response with organelle-specific Peptide conjugates. AB - Oxidative stress is a deleterious force that must be combated relentlessly by aerobic organisms and is known to underlie many human diseases including atherosclerosis, Parkinson's disease, and Alzheimer's disease. Information available about the oxidative stress response has come primarily from studies using reactive oxygen species (ROS) with ill-defined locations within the cell. Thus, existing models do not account for possible differences between stress originating within particular regions of the cell. Here, oxidative stress is studied at the subcellular level using ROS-generating compounds localizing within two different organelles: the nucleus and the mitochondrion. Differences in cytotoxicity, gene expression, and survival pathway activation are detected as a function of the subcellular origin of oxidative stress, indicating that independent mechanisms are used to cope with oxidative stress arising in different cellular compartments. These comparative studies, enabled by the development of organelle-specific oxidants, examine the cellular responses to site-specific oxidative stress with heightened precision. PMID- 17719492 TI - Structural and mechanistic analysis of protein interactions in module 3 of the 6 deoxyerythronolide B synthase. AB - We report the 2.6 A X-ray crystal structure of a 190 kDa homodimeric fragment from module 3 of the 6-deoxyerthronolide B synthase covalently bound to the inhibitor cerulenin. The structure shows two well-organized interdomain linker regions in addition to the full-length ketosynthase (KS) and acyltransferase (AT) domains. Analysis of the substrate-binding site of the KS domain suggests that a loop region at the homodimer interface influences KS substrate specificity. We also describe a model for the interaction of the catalytic domains with the acyl carrier protein (ACP) domain. The ACP is proposed to dock within a deep cleft between the KS and AT domains, with interactions that span both the KS homodimer and AT domain. In conjunction with other recent data, our results provide atomic resolution pictures of several catalytically relevant protein interactions in this remarkable family of modular megasynthases. PMID- 17719494 TI - Improved mutasynthetic approaches for the production of modified aminocoumarin antibiotics. AB - This study reports improved mutasynthetic approaches for the production of aminocoumarin antibiotics. Previously, the mutasynthetic production of aminocoumarins with differently substituted benzoyl moieties was limited by the substrate specificity of the amide synthetase CloL. We expressed two amide synthetases with different substrate specificity, CouL and SimL, in appropriately engineered producer strains. After feeding of precursor analogs that were not accepted by CloL, but by SimL or CouL, a range of aminocoumarins, unattainable in our previous experiments, was produced and isolated in preparative amounts. Further, we developed a two-stage mutasynthesis procedure for the production of hybrid antibiotics that showed the substitution pattern of novobiocin in the aminocoumarin moiety and that of clorobiocin in the deoxysugar moiety. The substitution pattern of the benzoyl moiety was determined by external addition of an appropriate precursor. Twenty-five aminocoumarin compounds were prepared by these methods, and their structures were elucidated with mass and 1H-NMR spectroscopy. PMID- 17719493 TI - Interrogating the molecular basis for multiple macrolactone ring formation by the pikromycin polyketide synthase. AB - The pikromycin polyketide synthase (PKS) is unique in its ability to generate both 12 and 14 membered ring macrolactones. As such, dissection of the molecular basis for controlling metabolic diversity in this system remains an important objective for understanding modular PKS function and expanding chemical diversity. Here, we describe a series of experiments designed to probe the importance of the protein-protein interaction that occurs between the final two monomodules, PikAIII (module 5) and PikAIV (module 6), for the production of the 12 membered ring macrolactone 10-deoxymethynolide. The results obtained from these in vitro studies demonstrate that PikAIII and PikAIV generate the 12 membered ring macrocycle most efficiently when engaged in their native protein protein interaction. Accordingly, the data are consistent with PikAIV adopting an alternative conformation that enables the terminal thioesterase domain to directly off-load the PikAIII-bound hexaketide intermediate for macrocyclization. PMID- 17719506 TI - Fostering innovative use of disaster supplies. PMID- 17719507 TI - START triage: does it work? AB - BACKGROUND: A mass casualty incident (MCI) demands rapid and efficient triage of victims. The Simple Triage and Rapid Treatment (START) protocol has been proposed to identify salvageable victims from those with imminent mortality. This study evaluates the efficacy of START triage to predict likelihood of mortality of an MCI trauma victim. METHODS: Trauma patients were randomly selected using the trauma database at a local Level II trauma center. Survival was defined as a discharge from the hospital with the primary endpoint being death. For respiratory rate <30, pulse <100, and Glasgow Coma Scale score >14, one point was given to the victim for each category. Persons who did not meet these criteria were given a score of zero. The scores were then tabulated and analyzed with respect to the primary endpoint. RESULTS: Of the 355 persons analyzed, 341 (96%) survived and 14 (3.9%) were categorized as deceased. For patients with a tabulated score /=2, the PPV and NPV were 0.08 and 0.99, respectively. DISCUSSION: Of the total victims, 75.77% with a respiratory rate <30, palpable radial pulse, and intact mental status survived. The deceased victims with tabulated scores of 1, 2, and 3 had mortalities of 50%, 28%, and 21%, respectively. The trend toward lower tabulated scores in the deceased victims suggests efficacy with START triage. PMID- 17719508 TI - Organization-based incident management: developing a disaster volunteer role on a university campus. AB - BACKGROUND: Catastrophic events are an ongoing part of life, affecting society both locally and globally. Recruitment, development, and retention of volunteers who offer their knowledge and skills in the event of a disaster are essential to ensuring a functional workforce during catastrophes. These opportunities also address the inherent need for individuals to feel necessary and useful in times of crisis. Universities are a particularly important setting for voluntary action, given that they are based in communities and have access to resources and capabilities to bring to bear on an emergency situation. METHODS: The purpose of the study was to discern how one large private organization might participate and respond in the case of a large scale disaster. Using a 2-phase random sample survey, 337 unique respondents (5.7%) out of a sample of 6000 replied to the survey. RESULTS: These data indicate that volunteers in a private organization are willing to assist in disasters and have skills that can be useful in disaster mitigation. DISCUSSION: Much is to be learned related to the deployment of volunteers during disaster. These findings suggest that volunteers can and will help and that disaster preparedness drills are a logical next step for university based volunteers. PMID- 17719510 TI - Establishing a prophylactic drug dispensing clinic: the University of Rhode Island model. AB - The purpose of this guide is to assist community and university planners in developing and implementing a medication Point of Dispensing plan and conducting a Point of Dispensing drill. Key planning strategies addressed include community assessment, resource coordination, community partnerships, physical plant considerations, and multifunction considerations that will assist community planners to better prepare for bioterrorism or naturally occurring infectious disease events. PMID- 17719509 TI - Assessment of physician preparedness and response capacity to bioterrorism or other public health emergency events in a major metropolitan area. AB - BACKGROUND: The role of physicians in the detection, reporting, and response to infectious disease outbreaks, anomalous biologic events, or other public health emergencies is critical to the community's safety. OBJECTIVE/METHOD: In an effort to assess the level of preparedness of local physicians to respond to such events, the City of Fort Worth Public Health Department, the Fort Worth/Tarrant County Health Authority, and the Tarrant County Medical Society collaborated in designing and administering a cross-sectional study in spring 2006. RESULTS: The results serve as a baseline of the local clinical community's preparedness, with 91% of local physicians reporting their knowledge as "fair-poor," 80% desiring more information, and 83% favoring more training opportunities. CONCLUSION: Information obtained through this assessment is used to help cultivate educational interventions that will enhance the participation, integration, and mobilization of clinicians in the event of a community emergency. PMID- 17719511 TI - Predictors of long-acting opioid use and oral versus transdermal route among older Medicaid beneficiaries. AB - BACKGROUND: The availability of long-acting (LA) opioid medications represents an advance in the treatment of persistent pain, raising the question of what factors predict receipt of this newer treatment approach. OBJECTIVE: This study sought to determine which factors predict use of LA opioid medications and which factors predict use of transdermal versus oral options in an older population. METHODS: A retrospective analysis was conducted of Medicaid claims from May 1999 to April 2002 for older (aged >60 years) Kansas Medicaid beneficiaries receiving opioid medications equivalent to >or=600 mg of morphine per month. Demographic data, diagnoses, and medication use were derived from Medicaid claims data provided by the Kansas Department of Social and Rehabilitative Services to Dr. Shireman for a larger project. Bivariate analyses and multivariable models were used to determine which clinical and demographic factors predicted LA opioid use in general and which factors were associated with transdermal fentanyl (TDF) use in particular. RESULTS: The study population was mostly women, and more than one third were aged >85 years. Of the 766 claims, those patients taking LA opioids (n = 352) received oral sustained-release morphine, oral controlled-release oxycodone, or the TDF patch, with or without concomitant short-acting (SA) opioids. All others received SA opioids only (n = 414). In multivariate analysis, LA opioid use was more common among nursing home residents (adjusted odds ratio [AOR] = 1.45; 95% CI, 1.04-2.02) and persons under hospice care (AOR = 2.10; 95% CI, 1.19-3.73), with malignancy also bordering on a statistically significant association (AOR = 1.63; 95% CI, 1.00-2.66). Age, sex, race/ethnicity, and urban/nonurban residence were not associated with LA opioid use. Among those taking LA opioids, TDF use was more likely with older age (AOR = 2.89; 95% CI, 1.44-5.81 for aged >or=85 years vs aged 60-75 years), nursing home residence (AOR = 2.51; 95% CI, 1.46-4.49), dementia (AOR = 2.77; 95% CI, 1.03-7.48), malignancy (AOR = 3.03; 95% CI, 1.25-7.34), and nonwhite race (AOR = 2.72; 95% CI, 1.18 6.28), and less likely with chronic obstructive pulmonary disease (AOR = 0.47; 95% CI, 0.26-0.88), in adjusted analysis. CONCLUSIONS: Demographic and clinical predictors of TDF use differed from predictors of any LA opioid use among these older Medicaid beneficiaries. Qualitative research methods are needed to better understand what factors influence selection of opioid medications for older patients in nursing homes and community settings. PMID- 17719512 TI - Medication adherence and health care costs with the introduction of latanoprost therapy for glaucoma in a Medicare managed care population. AB - BACKGROUND: Latanoprost, a prostaglandin inhibitor, is increasingly being used in the therapeutic management of glaucoma. However, there is scant literature examining the cost and outcome ramifications of latanoprost. OBJECTIVES: This study examined the medication use behavior (medication-related persistence and adherence rates) and costs associated with the introduction of latanoprost therapy in a treatment-naive older population (aged >or=65 years) enrolled in Medicare. METHODS: The study employed a retrospective observational cohort design and used administrative claims data from a Medicare health maintenance organization (HMO), which offered complete coverage to enrollees, including prescription benefits. The case group consisted of patients with glaucoma who began latanoprost therapy. The control group consisted of enrollees with glaucoma who started any therapy other than latanoprost. Both groups were followed up for 1 year before and after initiation of therapy. Bivariate and multivariate techniques incorporating health care utilization in the year before the start of new therapy were used to determine the study outcomes. RESULTS: The case group comprised 101 patients (mean age, 77.60 years), while the control group included 168 patients (mean age, 77.59 years). There were no significant differences across the 2 groups with respect to age, sex, general health scores on the 12 item Short-Form Health Survey, severity of comorbidity, or the proportion of respondents with perception of worsened health. Introduction of latanoprost therapy was associated with higher medication persistence (hazard ratio, 0.90; 95% CI, 0.68-0.98) and adherence rates (mean [SD], 0.51 [0.26] vs 0.40 [0.25]; P < 0.001) compared with patients starting other glaucoma medication. Furthermore, there were no additional increases in total health care costs in the entire population associated with the introduction of latanoprost therapy, after adjusting for group and time effects, as well as other confounders (mean [SD], $4718.24 [$8982.92] vs $4046.55 [$6505.39]). CONCLUSIONS: Latanoprost therapy offered improved medication use behavior in these older adults enrolled in a Medicare HMO. There were no significant additional increases in overall health care costs as a result of introduction of latanoprost therapy, after adjusting for group and time effects, as well as other baseline confounders in this study cohort. PMID- 17719513 TI - Assessment of tolerability in elderly patients: changing to lamotrigine therapy. AB - BACKGROUND: Of all age groups, adults older than 75 years have the highest risk of seizures, especially partial seizures. In the past, physicians commonly used phenytoin, carbamazepine, and valproic acid as antiepileptic drugs (AEDs) in the elderly. However, these AEDs have potential adverse effects and drug interactions that may make them less desirable than newer AEDs for this age group. OBJECTIVES: The primary objective of this study was to assess the effects of changing the AED regimen to lamotrigine (LTG) in elderly patients (aged >or=60 years) who were initially unsatisfied with their drug regimen because of adverse effects or continuing seizures. These patients comprised a subgroup from a multicenter, open label trial of partial-seizure patients who switched to LTG. Other objectives included assessing the change in quality of life in patients taking LTG as adjunctive therapy and as monotherapy, and evaluating the efficacy of LTG for seizures when used as adjunctive treatment and as monotherapy. METHODS: The study involved 2 phases: LTG was first added to the regimen, and then patients could change to LTG monotherapy. Tolerability, the primary end point, was assessed using the Liverpool Adverse Experience Profile (AEP). Secondary end points included quality of life, as measured with the Quality of Life in Epilepsy-31 inventory, investigator global assessment, patient's self-rated satisfaction with treatment, and Profile of Mood States. The proportion of patients who completed each phase with at least a 50% reduction in seizures from baseline and the proportion of patients remaining seizure free throughout each phase were also determined. RESULTS: Sixty-two patients aged >or=60 years (mean [SD]age, 71.3 [7.6] years; 31 men, 31 women) were enrolled. After adding LTG, older patients reported fewer adverse effects, improved mood, better quality of life, and fewer seizures. Changing to LTG as monotherapy produced further improvement in all measurements. For the primary end point, mean improvement in AEP scores from baseline was 2.3 at the end of the adjunctive therapy phase (P = 0.027) and 5.7 by the end of the monotherapy phase (P < 0.005). In addition, there was a mean improvement of 2.0 in the AEP score from the adjunctive therapy to the monotherapy phase. CONCLUSIONS: For older patients with seizures who were unhappy with their AED regimen because of adverse effects, continuing seizures, or both, adding LTG to the drug regimen was associated with improved tolerability and effectiveness, and switching to LTG monotherapy was associated with further improvement. PMID- 17719514 TI - Use of wet nebulized inhaled respiratory medications under criteria-based reimbursement guidelines in a publicly funded Seniors' Pharmacare Program in Nova Scotia, Canada. AB - BACKGROUND: During the 1999/2000 fiscal year, approximately 19% of beneficiaries in the Nova Scotia Seniors' Pharmacare Program (NSSPP), a publicly funded drug insurance program in Nova Scotia, Canada, received inhaled respiratory medications by wet nebulization. The cost was estimated at more than Can $2 million annually. On August 1, 2000, the NSSPP initiated new criteria-based reimbursement guidelines for wet nebulized respiratory medications, requiring prior authorization. OBJECTIVE: Within the NSSPP, we examined approved reimbursement requests to determine demographic characteristics of those who accessed wet nebulized therapy through exception criteria, compare these factors between those who accessed wet nebulized therapy within the exception criteria and those who fell outside the criteria, identify indications for use of wet nebulization, and determine patterns of wet nebulization use. METHODS: Two hundred approved requests, received between August 1, 2000, and April 30, 2001, were randomly selected and reviewed for indications and patterns of use. RESULTS: Of 200 requests reviewed, 28 were excluded due to coverage in another Pharmacare program (Community Services). Of the 172 requests reviewed, 27% were for nursing home or other residential care facility residents. Indications and patterns of use differed only by place of residence (P<0.001). The majority of indications (72%) fell within outlined reimbursement criteria, with the most frequently cited indication (56%) being inability to use portable inhalers due to cognitive or physical disability. Almost one third (28%) of exception requests were approved for other reasons (31% of these were for short-term use [ie, <3 months] secondary to an acute respiratory infection or for palliative care; 69% continued to access wet nebulization because of a preference or a perception of greater effectiveness). Examination of patterns of use demonstrated that 36% of beneficiaries, primarily community dwelling (P < 0.001), were using wet nebulized therapy and portable inhalers concurrently. CONCLUSIONS: The majority of approved requests for wet nebulization criteria fell within the established reimbursement guidelines. Many approvals outside of guidelines were clinically valid. Approval of requests outside the criteria highlights the need for flexibility in the claims administrative and adjudication system to respond to unique circumstances not covered by established criteria. However, concurrent use of wet nebulization and portable inhalers by some beneficiaries suggests suboptimal use of portable inhalers, the need for portable inhalers for patients using wet nebulization when they leave their residence, and the need for more patient education. PMID- 17719515 TI - Prophylaxis for opioid-induced constipation in elderly long-term care residents: a cross-sectional study of Medicare beneficiaries. AB - BACKGROUND: Opioid analgesics are effective therapeutic agents for malignant and nonmalignant pain, but their use is often compromised by unwanted adverse effects on the central nervous system and gastrointestinal (GI) tract. These adverse effects include sedation, respiratory depression, nausea and vomiting, reduction in biliary and pancreatic secretions, decreased GI motility, increased GI transit time, and subsequent constipation. OBJECTIVE: The goal of this study was to determine national estimates of laxative use, with and without concurrent opioids, in the long-term care (LTC) population and to determine factors associated with laxative underuse among elderly LTC residents receiving opioids. METHODS: This cross-sectional study was conducted in LTC facilities in the United States. Medicare beneficiaries participating in the Medicare Current Beneficiary Survey (MCBS) aged >or=65 years residing at least 1 month in a nursing home or assisted living facility in 2001 were considered eligible. Monthly and annual measures of laxative and opioid use were developed to estimate prevalence of drug use in the LTC population. Multivariable logistic regression was used to determine factors associated with the use of laxatives. RESULTS: Among our sample of 867 MCBS beneficiaries (mean [SD]age, 85.0 [7.7] years), 281 (32%) received at least 1 opioid at some time during 2001. Of these 281 patients, 186 (66%) were administered at least 1 laxative at any time of the year. We found that the mean monthly prevalence of concurrent opioid and laxative use was 55% (476/867). There was a low prevalence of as-needed laxative and opioid use; 96% of resident-months were identified as scheduled bowel regimen administrations, and 89% of resident months with opioid use had >or=3 opioid administrations. The results of the multivariable analysis showed that white, female, and currently married patients spend 227% (P < 0.007), 52% (p < 0.008), and 39% (P < 0.02), respectively, more months with at least 1 administration of a laxative and an opioid than their counterpart nonwhite, male, unmarried patients, Comorbidities were not associated with laxative prophylaxis. CONCLUSION: Although laxatives are widely recommended in patients taking opioids, only 66% of elderly LTC residents in this study received this standard of care. PMID- 17719516 TI - A retrospective study of the association between megestrol acetate administration and mortality among nursing home residents with clinically significant weight loss. AB - BACKGROUND: Megestrol acetate (MA) is a progestin widely used to treat weight loss and cachexia in patients suffering from AIDS or cancer. Although MA is also frequently prescribed for similarly malnourished elderly individuals, the efficacy and morbidity of MA treatment in this patient population remain unclear. OBJECTIVE: The goal of this study was to examine the effects of MA therapy on weight and overall mortality in elderly nursing home residents. METHODS: This was a case-control cohort study of 17,328 nursing home residents admitted to Beverly Healthcare nursing home between January 1, 2000, and December 31, 2003, who had lost either 5% of total body weight within 3 months or 10% of total body weight within 6 months. Residents within this weight loss group who received MA therapy- within 30 days of their weight loss documentation--were matched (1:2) with non-MA treated residents with respect to age, sex, race, weight, and first notation of weight loss. Residents were further matched by propensity score for activities of daily living, cognitive functioning, number of medications taken during the 7 days before data entry, clinical condition (unstable, acute episode of a recurrent problem, end-stage disease), cancer diagnosis, and human immunodeficiency virus diagnosis. RESULTS: A total of 709 patients (mean [SD]age, 84.1 [9.7]years; 70.9% female) who received MA therapy were matched with 1418 non MA-treated patients (mean [SD] age, 84.2 [9.0] years; 70.9% female). Of the 709 MA patients, 281 (39.6%) were alive and in the nursing home at last follow-up, 149 (21.0%) were alive and discharged to another facility or to home, and 279 (39.4%) died in the nursing home. For the controls, 651 (45.9%) were alive and in the nursing home, 308 (21.7%) were discharged to another facility or to home, and 459 (32.4%) died in the nursing home. The median survival of MA-treated residents (23.9 months; 95% CI, 20.2-27.5) was significantly less than untreated residents (31.2 months; 95% CI, 27.8-35.9) (P < 0.001). Median weight and median of weight differences were unchanged after 6 months of treatment with MA compared with matched controls. CONCLUSIONS: MA treatment of elderly nursing home residents with significant weight loss was associated with a significant increase in all cause mortality without a significant increase in weight. Randomized, prospective studies of the use of MA in elderly nursing home residents are necessary to more fully evaluate morbidity and mortality associated with this therapy. PMID- 17719517 TI - Sex differences in inappropriate prescribing among elderly veterans. AB - BACKGROUND: Previous studies have suggested that older women may be more likely than older men to receive potentially inappropriate prescriptions. A better understanding of sex differences in inappropriate prescribing can help inform the development of effective interventions. OBJECTIVE: This study was conducted to assess sex differences in rates of inappropriate prescribing before and after accounting for potentially appropriate indications and to examine sex differences in predictors of inappropriate drug use. METHODS: This was a retrospective cohort study of administrative data from the national Veterans Health Administration (VA). Participants were veterans aged >or=65 years who had >or=1 patient visit at VA outpatient facilities in fiscal year 1999 (FY99) and 2000 (FY00). The main outcome measure was the diagnosis-adjusted prevalence of 33 potentially inappropriate medications as judged by the Beers criteria in FY00: overall, by individual drug, and in 3 categories grouped by potential indication ("always avoid," "rarely appropriate," and "some indications"). RESULTS: The study population included 965,756 patients (946,641 men and 19,115 women). Women were more likely than men to receive inappropriate medications overall and in all 3 categories, even after accounting for diagnoses that may have justified the prescription. Women were more likely to receive 16 of the 33 medications (analgesics, psychotropic drugs, and anticholinergic agents), and men were more likely to receive 3 of the 33. After controlling for sociodemographic characteristics, number of medications, and care characteristics, women remained more likely to receive inappropriate drugs. Receipt of geriatric care was equally protective for men and women, although only a small proportion received this care. Psychiatric comorbidity was associated with inappropriate prescribing for men but not for women. CONCLUSIONS: Analgesic, psychotropic, and anticholinergic medications that should be avoided contributed to higher rates of inappropriate drug use among older women than among older men. Targeted efforts to avoid these medications in older women may help reduce overall rates of inappropriate prescribing. Sex-stratified reporting of quality indicators that assess inappropriate prescribing among community-dwelling elders would help monitor the effectiveness of improvement efforts. PMID- 17719518 TI - Dextromethorphan-induced near-fatal suicide attempt in a slow metabolizer at cytochrome P450 2D6. AB - BACKGROUND: Dextromethorphan (DXM) is a common ingredient in several prescriptions and over-the-counter cough preparations. Its metabolism in humans includes hepatic O- and N-demethylation to form dextrorphan and 3 methoxymorphinan, respectively, followed by conjugation. The active metabolite dextrorphan is a noncompetitive N-methyl-D-aspartate receptor antagonist that has been linked with psychosis, especially in rapid metabolizers at cytochrome P450 (CYP) 2D6. CASE SUMMARY: The patient was a 66-year-old married, retired Portuguese American male, with no prior psychiatric history. He presented to the emergency department following a brief psychotic episode leading to a near-fatal suicide attempt after ingesting an excessive quantity of DXM. The patient had started by ingesting 3 tablespoons (45 mL) of cough syrup per day (total, 1575 mg/d) instead of the prescribed 3 teaspoons (15 mL). In the days preceding the admission, his frequency of use had increased substantially (up to 6 times per day). During the treatment of this episode, he was initially started on sertraline 50 mg/d, which was discontinued within 48 hours, given the lack of depressive symptoms, and risperidone was initiated at 1 mg BID. The medication was discontinued after several months, and the patient completely recovered. Possible medical and psychiatric etiologies related to this brief psychotic episode in a geriatric patient are also discussed. CONCLUSIONS: Caution should be exercised in prescribing DXM to geriatric patients, as they may be more susceptible to the drug's adverse effects because of increased clearance time. It appears that dose may play a greater role in causing psychosis, rather than the rate of metabolism, as evident in our patient who, contrary to the more often described scenario, was a slow metabolizer at CYP2D6. PMID- 17719520 TI - Rasagiline as a therapy for Parkinson's disease (PD). PMID- 17719533 TI - microRNAs: a safeguard against turmoil? AB - Emerging data suggest that microRNAs (miRNAs) are instrumental in a variety of stress responses in addition to their more recognized role in development. Surprisingly, miRNAs, which normally suppress expression of target transcripts, may become activators of expression during stress. This might be partially explained by new interactions of miRNA/Argonaute complexes with RNA-binding proteins that relocate from different subcellular compartments during stress. PMID- 17719534 TI - The long and short of fatty acid synthesis. AB - The multienzyme complex that synthesizes very long chain fatty acids is embedded in the membrane of the endoplasmic reticulum. In this issue, Denic and Weissman (2007) describe the reconstitution of this complex in liposomes and reveal how elongase proteins (Elops) determine the final length of the fatty acyl CoA chain. PMID- 17719535 TI - Innate immune response triggers lupus-like autoimmune disease. AB - Autoimmune disease is typically defined as an aberrant response of lymphocytes to self antigens that ultimately leads to tissue damage. Reporting in Immunity, Green et al. (2007) now show that mice lacking alpha-mannosidase II develop an autoimmune disease similar to lupus. Remarkably, this illness is precipitated by an innate immune response to altered self glycans that mimic molecular patterns found on pathogens. PMID- 17719536 TI - The VEGF family, the inside story. AB - The role of paracrine signaling by vascular endothelial growth factor (VEGF) in the formation and maintenance of blood vessels has been studied extensively. In this issue, Lee et al. (2007) report unexpected results showing that endogenous VEGF produced by endothelial cells is also crucial for vascular homeostasis. PMID- 17719537 TI - Should I stay or should I go: Wnt signals at the synapse. AB - Several extracellular factors, including Wnt proteins, have been reported to induce synapse formation. In this issue, Klassen and Shen (2007) report that Wnt proteins can also act as antisynaptogenic signals to prevent synapse formation in certain parts of the worm Caenorhabditis elegans. The differential response of axon populations to local Wnt proteins may contribute to the patterning of synaptic connections. PMID- 17719538 TI - Living with p53, dying of p53. AB - The p53 tumor suppressor protein acts as a major defense against cancer. Among its most distinctive features is the ability to elicit both apoptotic death and cell cycle arrest. In this issue of Cell, Das et al. (2007) and Tanaka et al. (2007) provide new insights into the mechanisms that dictate the life and death decisions of p53. PMID- 17719539 TI - Modeling tissue morphogenesis and cancer in 3D. AB - Three-dimensional (3D) in vitro models span the gap between two-dimensional cell cultures and whole-animal systems. By mimicking features of the in vivo environment and taking advantage of the same tools used to study cells in traditional cell culture, 3D models provide unique perspectives on the behavior of stem cells, developing tissues and organs, and tumors. These models may help to accelerate translational research in cancer biology and tissue engineering. PMID- 17719540 TI - A bacterial effector targets Mad2L2, an APC inhibitor, to modulate host cell cycling. AB - The gut epithelium self-renews every several days, providing an important innate defense system that limits bacterial colonization. Nevertheless, many bacterial pathogens, including Shigella, efficiently colonize the intestinal epithelium. Here, we show that the Shigella effector IpaB, when delivered into epithelial cells, causes cell-cycle arrest by targeting Mad2L2, an anaphase-promoting complex/cyclosome (APC) inhibitor. Cyclin B1 ubiquitination assays revealed that APC undergoes unscheduled activation due to IpaB interaction with the APC inhibitor Mad2L2. Synchronized HeLa cells infected with Shigella failed to accumulate Cyclin B1, Cdc20, and Plk1, causing cell-cycle arrest at the G2/M phase in an IpaB/Mad2L2-dependent manner. IpaB/Mad2L2-dependent cell-cycle arrest by Shigella infection was also demonstrated in rabbit intestinal crypt progenitors, and the IpaB-mediated arrest contributed to efficient colonization of the host cells. These results strongly indicate that Shigella employ special tactics to influence epithelial renewal in order to promote bacterial colonization of intestinal epithelium. PMID- 17719541 TI - Hzf Determines cell survival upon genotoxic stress by modulating p53 transactivation. AB - A critical unresolved issue about the genotoxic stress response is how the resulting activation of the p53 tumor suppressor can lead either to cell-cycle arrest and DNA repair or to apoptosis. We show here that hematopoietic zinc finger (Hzf), a zinc-finger-containing p53 target gene, modulates p53 transactivation functions in an autoregulatory feedback loop. Hzf is induced by p53 and binds to its DNA-binding domain, resulting in preferential transactivation of proarrest p53 target genes over its proapoptotic target genes. Thus, p53 activation results in cell-cycle arrest in Hzf wild-type MEFs, while in Hzf(-/-) MEFs, apoptosis is induced. Exposure of Hzf null mice to ionizing radiation resulted in enhanced apoptosis in several organs, as compared to in wild-type mice. These findings provide novel insights into the regulation of p53 transactivation function and suggest that Hzf functions as a key player in regulating cell fate decisions in response to genotoxic stress. PMID- 17719542 TI - hCAS/CSE1L associates with chromatin and regulates expression of select p53 target genes. AB - The p53 tumor suppressor protein regulates many genes that can determine different cellular outcomes such as growth arrest or cell death. Promoter selective transactivation by p53, although critical for the different cellular outcomes, is not well understood. We report here that the human cellular apoptosis susceptibility protein (hCAS/CSE1L) associates with a subset of p53 target promoters, including PIG3, in a p53-autonomous manner. Downregulation of hCAS/CSE1L decreases transcription from those p53 target promoters to which it preferentially binds and reduces apoptosis. In addition, hCAS/CSE1L silencing leads to increased methylation of histone H3 lysine 27 within the PIG3 gene. hCAS/CSE1L was previously shown to function as a nucleo-cytoplasmic transport factor, as does its closely related yeast homologue Cse1, which can also associate with chromatin and serve as a barrier protein that prevents spreading of heterochromatin. Thus, human CAS/CSE1L can bind select genes with significant functional consequences for p53-mediated transcription and determine cellular outcome. PMID- 17719543 TI - Autoinhibition of the HECT-type ubiquitin ligase Smurf2 through its C2 domain. AB - Ubiquitination of proteins is an abundant modification that controls numerous cellular processes. Many Ubiquitin (Ub) protein ligases (E3s) target both their substrates and themselves for degradation. However, the mechanisms regulating their catalytic activity are largely unknown. The C2-WW-HECT-domain E3 Smurf2 downregulates transforming growth factor-beta (TGF-beta) signaling by targeting itself, the adaptor protein Smad7, and TGF-beta receptor kinases for degradation. Here, we demonstrate that an intramolecular interaction between the C2 and HECT domains inhibits Smurf2 activity, stabilizes Smurf2 levels in cells, and similarly inhibits certain other C2-WW-HECT-domain E3s. Using NMR analysis the C2 domain was shown to bind in the vicinity of the catalytic cysteine, where it interferes with Ub thioester formation. The HECT-binding domain of Smad7, which activates Smurf2, antagonizes this inhibitory interaction. Thus, interactions between C2 and HECT domains autoinhibit a subset of HECT-type E3s to protect them and their substrates from futile degradation in cells. PMID- 17719544 TI - A molecular caliper mechanism for determining very long-chain fatty acid length. AB - Very long-chain fatty acids (VLCFAs) are essential lipids whose functional diversity is enabled by variation in their chain length. The full VLCFA biosynthetic machinery and how this machinery generates structural diversity remain elusive. Proteoliposomes reconstituted here from purified membrane components-an elongase protein (Elop), a novel dehydratase, and two reductases catalyzed repeated rounds of two-carbon addition that elongated shorter FAs into VLCFAs whose length was dictated by the specific Elop homolog present. Mutational analysis revealed that the Elop active site faces the cytosol, whereas VLCFA length is determined by a lysine near the luminal end of an Elop transmembrane helix. By stepping the lysine residue along one face of the helix toward the cytosol, we engineered novel synthases with correspondingly shorter VLCFA outputs. Thus the distance between the active site and the lysine residue determines chain length. Our results uncover a mutationally adjustable, caliper like mechanism that generates the repertoire of cellular VLCFAs. PMID- 17719545 TI - Cep97 and CP110 suppress a cilia assembly program. AB - Mammalian centrioles play a dynamic role in centrosome function, but they also have the capacity to nucleate the assembly of cilia. Although controls must exist to specify these different fates, the key regulators remain largely undefined. We have purified complexes associated with CP110, a protein that plays an essential role in centrosome duplication and cytokinesis, and have identified a previously uncharacterized protein, Cep97, that recruits CP110 to centrosomes. Depletion of Cep97 or expression of dominant-negative mutants results in CP110 disappearance from centrosomes, spindle defects, and polyploidy. Remarkably, loss of Cep97 or CP110 promotes primary cilia formation in growing cells, and enforced expression of CP110 in quiescent cells suppresses their ability to assemble cilia, suggesting that Cep97 and CP110 collaborate to inhibit a ciliogenesis program. Identification of Cep97 and other genes involved in regulation of cilia assembly may accelerate our understanding of human ciliary diseases, including renal disease and retinal degeneration. PMID- 17719546 TI - Autocrine VEGF signaling is required for vascular homeostasis. AB - Vascular endothelial growth factor (VEGF) is essential for developmental and pathological angiogenesis. Here we show that in the absence of any pathological insult, autocrine VEGF is required for the homeostasis of blood vessels in the adult. Genetic deletion of vegf specifically in the endothelial lineage leads to progressive endothelial degeneration and sudden death in 55% of mutant mice by 25 weeks of age. The phenotype is manifested without detectable changes in the total levels of VEGF mRNA or protein, indicating that paracrine VEGF could not compensate for the absence of endothelial VEGF. Furthermore, wild-type, but not VEGF null, endothelial cells showed phosphorylation of VEGFR2 in the absence of exogenous VEGF. Activation of the receptor in wild-type cells was suppressed by small molecule antagonists but not by extracellular blockade of VEGF. These results reveal a cell-autonomous VEGF signaling pathway that holds significance for vascular homeostasis but is dispensable for the angiogenic cascade. PMID- 17719547 TI - Wnt signaling positions neuromuscular connectivity by inhibiting synapse formation in C. elegans. AB - Nervous system function is mediated by a precisely patterned network of synaptic connections. While several cell-adhesion and secreted molecules promote the assembly of synapses, the contribution of signals that negatively regulate synaptogenesis is not well understood. We examined synapse formation in the Caenorhabditis elegans motor neuron DA9, whose presynapses are restricted to a specific segment of its axon. We report that the Wnt lin-44 localizes the Wnt receptor lin-17/Frizzled (Fz) to a subdomain of the DA9 axon that is devoid of presynaptic specializations. When this signaling pathway, composed of the Wnts lin-44 and egl-20, lin-17/Frizzled and dsh-1/Dishevelled, is compromised, synapses develop ectopically in this subdomain. Conversely, overexpression of LIN 44 in cells adjacent to DA9 is sufficient to expand LIN-17 localization within the DA9 axon, thereby inhibiting presynaptic assembly. These results suggest that morphogenetic signals can spatially regulate the patterning of synaptic connections by subdividing an axon into discrete domains. PMID- 17719548 TI - Growing dendrites and axons differ in their reliance on the secretory pathway. AB - Little is known about how the distinct architectures of dendrites and axons are established. From a genetic screen, we isolated dendritic arbor reduction (dar) mutants with reduced dendritic arbors but normal axons of Drosophila neurons. We identified dar2, dar3, and dar6 genes as the homologs of Sec23, Sar1, and Rab1 of the secretory pathway. In both Drosophila and rodent neurons, defects in Sar1 expression preferentially affected dendritic growth, revealing evolutionarily conserved difference between dendritic and axonal development in the sensitivity to limiting membrane supply from the secretory pathway. Whereas limiting ER-to Golgi transport resulted in decreased membrane supply from soma to dendrites, membrane supply to axons remained sustained. We also show that dendritic growth is contributed by Golgi outposts, which are found predominantly in dendrites. The distinct dependence between dendritic and axonal growth on the secretory pathway helps to establish different morphology of dendrites and axons. PMID- 17719549 TI - Intrinsic circadian clock of the mammalian retina: importance for retinal processing of visual information. AB - Circadian clocks are widely distributed in mammalian tissues, but little is known about the physiological functions of clocks outside the suprachiasmatic nucleus of the brain. The retina has an intrinsic circadian clock, but its importance for vision is unknown. Here we show that mice lacking Bmal1, a gene required for clock function, had abnormal retinal transcriptional responses to light and defective inner retinal electrical responses to light, but normal photoreceptor responses to light and retinas that appeared structurally normal by light and electron microscopy. We generated mice with a retina-specific genetic deletion of Bmal1, and they had defects of retinal visual physiology essentially identical to those of mice lacking Bmal1 in all tissues and lacked a circadian rhythm of inner retinal electrical responses to light. Our findings indicate that the intrinsic circadian clock of the retina regulates retinal visual processing in vivo. PMID- 17719550 TI - Rac-GAP alpha-chimerin regulates motor-circuit formation as a key mediator of EphrinB3/EphA4 forward signaling. AB - The ephrin/Eph system plays a central role in neuronal circuit formation; however, its downstream effectors are poorly understood. Here we show that alpha chimerin Rac GTPase-activating protein mediates ephrinB3/EphA4 forward signaling. We discovered a spontaneous mouse mutation, miffy (mfy), which results in a rabbit-like hopping gait, impaired corticospinal axon guidance, and abnormal spinal central pattern generators. Using positional cloning, transgene rescue, and gene targeting, we demonstrated that loss of alpha-chimerin leads to mfy phenotypes similar to those of EphA4(-/-) and ephrinB3(-/-) mice. alpha-chimerin interacts with EphA4 and, in response to ephrinB3/EphA4 signaling, inactivates Rac, which is a positive regulator of process outgrowth. Moreover, downregulation of alpha-chimerin suppresses ephrinB3-induced growth cone collapse in cultured neurons. Our findings indicate that ephrinB3/EphA4 signaling prevents growth cone extension in motor circuit formation via alpha-chimerin-induced inactivation of Rac. They also highlight the role of a Rho family GTPase-activating protein as a key mediator of ephrin/Eph signaling. PMID- 17719551 TI - SnapShot: small RNA-mediated epigenetic modifications. PMID- 17719552 TI - L1 effects on the processing of inflected nouns in L2. AB - This study investigated the effect of L1 on the recognition of L2 Swedish inflected nouns. Two groups of late L2 learners with typologically very different native languages, Hungarian (agglutinative) and Chinese (isolating), participated in a visual lexical decision experiment. The target words were matched inflected vs. monomorphemic nouns from three frequency levels. The Hungarian group showed a morphological processing cost (longer reaction times for the inflected words) for low and medium frequency words but not for high frequency words, suggesting morphological decomposition of low and medium frequency Swedish inflected nouns. In contrast, for the Chinese group the reaction times of the inflected vs. monomorphemic words were similar at all frequency levels, indicating full-form processing of all the inflected nouns. This cross-language difference suggests that L1 can exert an effect on the morphological processing in L2. The application of full-form processing for the Swedish inflected nouns in the Chinese group might reflect strategy transfer from their isolating native language to Swedish. PMID- 17719553 TI - Helminth infections and risk factor analysis among residents in Eryuan county, Yunnan province, China. AB - Whilst infections with soil-transmitted helminths are common across China, the public-health significance of Schistosoma japonicum and food-borne helminths is more focalized. Only few studies have investigated the local epidemiology of helminth infections in rural China, including risk factor analysis. We collected stool and blood samples from 3220 individuals, aged 5-88 years, from 35 randomly selected villages in Eryuan county, Yunnan province, China. Stool samples were subjected to the Kato-Katz technique and examined for helminth eggs. Blood samples were tested for Trichinella spp., S. japonicum and cysticerci-specific antibodies. Data on individual and family-level risk factors were collected using questionnaires. The prevalence of Ascaris lumbricoides, Taenia spp., Trichuris trichiura and hookworms was 15.4%, 3.5%, 1.7% and 0.3%, respectively. The seroprevalence of Trichinella spp. was 58.8% and that of cysticercosis 18.5%. The egg positivity rate of S. japonicum in the 13 known endemic villages was 2.7%, and the corresponding seroprevalence was 49.5%. We observed a strong spatial heterogeneity in the families' economic status. S. japonicum infections were more prevalent among the Han than Bai nationality (odds ratio (OR)=3.77, 95% confidence interval (CI)=1.97-7.23) and tobacco growers (OR=3.66, 95% CI=1.77 7.60) and was only found at elevations below 2150 m above sea level. A. lumbricoides and Taenia spp. infections were more prevalent at altitudes above 2150 m when compared to lower settings (OR=1.51, 95% CI=1.24-1.84 and OR=5.32, 95% CI=3.42-8.28, respectively). The opposite was found for T. trichiura (OR=0.31, 95% CI=0.14-0.70). Our findings can guide the design and spatial targeting of control interventions against helminth infections in Eryuan county. PMID- 17719554 TI - Improved mathematical model for estimating H+ influx and H+ efflux in plant vacuolar vesicles acidified by ATPase or pyrophosphatase. AB - To adapt to environmental changes, plant cells very likely possess a biochemical system, using vacuoles, for maintaining cytoplasmic pH homeostasis. A simple approach is to estimate the active H(+) influx and H(+) efflux of isolated vacuolar vesicles, although there is no good mathematical model to describe H(+) flux. To establish a new quantitative model, vacuolar vesicles were isolated from hypocotyls of mung bean (Vigna radiata L.), and pyrophosphate (PPi)- or ATP dependent acidification was monitored using acridine orange. The change of pH inside the vesicles (pH(in)) was calculated using a pH calibration curve relating fluorescence quenching with DeltapH. After formation of a steady state DeltapH, passive H(+) efflux was monitored after terminating pumping with ethylenediaminetetraacetate, and the relative H(+) permeability coefficient (p(H+)) was calculated. The H(+) efflux simulated using the p(H+) corresponded to the H(+) efflux determined experimentally. H(+) influx was then calculated by subtracting the predicted H(+) efflux from the experimental net H(+) influx. H(+) influx into vesicles driven by H(+)-PPase or H(+)-ATPase decreased exponentially as the intravesicular pH(in) decreased, suggesting modulation of pumping by DeltapH, pH(in), or both. Finally, the PPi- or ATP-dependent H(+) accumulation determined experimentally was closely simulated by the predicted H(+) influx and H(+) efflux. The ability to predict H(+) flux under different conditions provides a powerful tool for studying pH homeostasis. PMID- 17719555 TI - Ergonomic design of beverage can lift tabs based on numerical evaluations of fingertip discomfort. AB - This paper introduces finite element analyses to evaluate numerically and objectively the feelings in the fingertip when opening aluminum beverage cans, in order to design the shape of the tab. Experiments of indenting vertically the fingertip pulp by a probe and by tabs of aluminum beverage can ends have allowed us to observe force responses and feelings in the fingertip. It was found that a typical force-displacement curve may be simplified as a combination of three curves with different gradients. Participants feel a touch at Curve 1 of the force-displacement curve, then feel a pressure and their pulse at Curve 2, finally feel discomfort followed by a pain in the fingertip at Curve 3. Finite element analyses have been performed to simulate indenting the tab with the fingertip vertically to confirm that the simulation results agree well with the experimental observations. Finally, numerical simulations of the finger pulling up the tab of the can end has also been performed and discomfort in the fingertip has been related to the maximum value of the contact stress of the finger model. Comparisons of three designs of tab ring shape showed that the tab with a larger contact area with finger is better. PMID- 17719557 TI - Fluid dynamics of gingiva and gingival health in children with end stage renal failure. AB - OBJECTIVES: Impaired homeostasis and fluid balance are important physiopathological alterations in patients with chronic renal failure which may adversely affect the fluid dynamics and health status of tissues and organs. There are insufficient data about this phenomenon in periodontal tissues. The aim of this study was to evaluate the fluid dynamics of gingiva in children with end stage renal failure (ESRF), correlating this entity with gingival health in the same patient group. DESIGN: Fifteen paediatric ESRF patients undergoing peritoneal dialysis (test group) and 15 systemically healthy children (control group) who were without periodontitis participated in the study. Fluid dynamics of gingiva were assessed via the gingival crevicular fluid (GCF) volume and tissue osmotic pressure (GOP) levels in the groups. GCF volume was measured using a Periotron 8000, whereas GOP was measured using a digital osmometer. Silness and Loe Plaque index (PI) and, Loe and Silness gingival index (GI) scores were utilized to determine the gingival health status in the study population. RESULTS: There were increases in the GCF volume and GOP of the test group compared to those of the control group (p<0.01). The PI and GI scores were higher in the test group than in the control group (p<0.01). Strong and positive correlations were found between GI and GCF volume, GI and GOP and, GCF volume and GOP in both groups (p<0.01). CONCLUSIONS: Our findings suggest that the fluid dynamics of gingiva may alter in children with ESRF, and this phenomenon may consequently affect the gingival health of these patients. PMID- 17719556 TI - Protein folding in confined and crowded environments. AB - Confinement and crowding are two major factors that can potentially impact protein folding in cellular environments. Theories based on considerations of excluded volumes predict disparate effects on protein folding stability for confinement and crowding: confinement can stabilize proteins by over 10k(B)T but crowding has a very modest effect on stability. On the other hand, confinement and crowding are both predicted to favor conformations of the unfolded state which are compact, and consequently may increase the folding rate. These predictions are largely borne out by experimental studies of protein folding under confined and crowded conditions in the test tube. Protein folding in cellular environments is further complicated by interactions with surrounding surfaces and other factors. Concerted theoretical modeling and test-tube and in vivo experiments promise to elucidate the complexity of protein folding in cellular environments. PMID- 17719558 TI - Bringing order to a complex molecular machine: the assembly of the bacterial flagella. AB - The bacterial flagellum is an example of elegance in molecular engineering. Flagella dependent motility is a widespread and evolutionarily ancient trait. Diverse bacterial species have evolved unique structural adaptations enabling them to migrate in their environmental niche. Variability exists in the number, location and configuration of flagella, and reflects unique adaptations of the microorganism. The most detailed analysis of flagellar morphogenesis and structure has focused on Escherichia coli and Salmonella enterica. The appendage assembles sequentially from the inner to the outer-most structures. Additionally the temporal order of gene expression correlates with the assembly order of encoded proteins into the final structure. The bacterial flagellar apparatus includes an essential basal body complex that comprises the export machinery required for assembly of the hook and flagellar filament. A review outlining the current understanding of the protein interactions that make up this remarkable structure will be presented, and the associated temporal genetic regulation will be briefly discussed. PMID- 17719559 TI - Attention focusing versus distraction during exposure in dental phobia. AB - A survey of the discrepant findings regarding the effects of attention focusing and distraction on exposure suggested that subjective measures of anxiety and avoidance respond better to the latter condition, and heart rate (HR) reaction responds to the former. To test this hypothesis, 63 dental phobics were recruited who had not visited a dentist for a mean of 6.6 (1.5-25) years. Participants received a 1-h exposure session with either attention focusing or distraction. Subjective anxiety and HR to phobia-related pictures were assessed before and after the treatment session and again after 1 week. Avoidance was recorded in terms of adherence to the dental treatment schedule in the following 6 months. Contrary to expectation, state anxiety showed a greater decrease in the attention focusing than the distraction condition after 1 week. Both treatment conditions were similarly effective with regard to HR and avoidance. HR habituated in both groups after exposure and 73% of followed-up patients adhered to the dental treatment schedule. Comparison of the present with previous results suggests that the differences between attentional conditions tend to be more pronounced during shorter exposure sessions than were employed in the present study. PMID- 17719560 TI - Bone morphogenetic protein. AB - Bone morphogenetic proteins (BMPs) are multi-functional growth factors belonging to the transforming growth factor-beta superfamily. It has been demonstrated that BMPs had been involved in the regulation of cell proliferation, survival, differentiation and apoptosis. However, their hallmark ability is that play a pivotal role in inducing bone, cartilage, ligament, and tendon formation at both heterotopic and orthotopic sites. In this review, we mainly concentrate on BMP structure, function, molecular signaling and potential medical application. PMID- 17719561 TI - Effect of ghrelin on human endothelial cells apoptosis induced by high glucose. AB - Endothelial dysfunction is thought to be a major cause of vascular complications in diabetes. Our research shows that ghrelin attenuates high glucose-induced apoptosis in cultured human umbilical vein endothelial cells (ECV-304). Exposure to glucose (33.3mM) for 72 h caused a significant increase in apoptosis, as evaluated by TUNEL and flow cytometry, but pretreatment of ghrelin (10(-7)M) eliminated high glucose-induced apoptosis in ECV-304. Ghrelin also prevented the induction of caspase-3 activation, in cells incubated with glucose (33.3 mM). Exposure of cells to ghrelin (10(-7)M) caused rapid activation of Akt. PI3K inhibitor, LY294002 attenuated ghrelin's inhibitory effect on caspase-3 activity. Ghrelin protected endothelial cells from high glucose by inhibiting reactive oxygen species (ROS) generation. Results of our study indicate that ghrelin inhibits both high glucose-induced apoptosis via PI3K/Akt pathway and ROS production in ECV-304. This peptide may have potential in preventing diabetic complications, especially in obese patients. PMID- 17719562 TI - KLF4 regulates the expression of interleukin-10 in RAW264.7 macrophages. AB - Kruppel-like factor 4 (KLF4) is an evolutionarily conserved zinc finger containing transcription factor. In the current study, RAW264.7 murine macrophages were treated with Escherichia coli lipopolysaccharide (LPS) to determine the expression of KLF4. A full-length cDNA or antisense oligonucleotides of KLF4 was transfected into RAW264.7 macrophages, and the expression and release of IL-10 were analyzed by RT-PCR and ELISA. The transcription and DNA binding activities of KLF4 to the IL-10 promoter were detected by the luciferase reporter and electrophoretic mobility shift assays. The results showed that treatment of RAW264.7 macrophages with LPS resulted in a dose- and time-dependent increase in KLF4 protein levels; KLF4 overexpression increased the expression of IL-10, while KLF4 inhibition decreased the expression of IL-10. The overexpression of KLF4 promoted the transcription and DNA binding activities of KLF4 to the IL-10 promoter. These results indicate that KLF4 plays an important role in regulating the expression of IL-10. PMID- 17719563 TI - YS 51, 1-(beta-naphtylmethyl)-6,7-dihydroxy-1,2,3,4,-tetrahydroisoquinoline, protects endothelial cells against hydrogen peroxide-induced injury via carbon monoxide derived from heme oxygenase-1. AB - Oxidative stress plays an important role in the pathophysiology of several vascular diseases such as atherosclerosis, and great attention has been placed on the protective role of heme oxygenase-1 (HO-1) for vasculature against oxidant induced injury. We tested whether the protective effects of YS 51, 1-(beta naphtyl-methyl)-6,7-dihydroxy-1,2,3,4,-tetrahydroisoquinoline, against hydrogen peroxide (H2O2)-induced cell injury is associated with HO-1 activity in bovine aortic endothelial cells (BAEC). YS 51 increased HO-1 expression and activity in concentration-dependent manners (10-100 microM) and time-dependent manners (1, 3, 6, 18 h), which were correlated well with its protective effect against H2O2 induced injury. Zinc protoporphyrin IX (ZnPP IX), a HO inhibitor, significantly inhibited the effect of YS 51 (50 microM). In contrast, [Ru(CO)3(Cl)2]2 (CORM-2, a CO releasing molecule) but not bilirubin protected against H2O2-induced injury. Oxyhemoglobin (HbO2) used as a CO scavenger significantly inhibited the protective effect of both YS 51 and CORM-2. Furthermore, both YS 51 and CORM-2 significantly reduced H2O2-induced intracellular reactive oxygen species (ROS) production; however, this was counteracted by ZnPP IX, HbO2 and deferoxamine. We found evidence for the involvement of PI3/Akt kinase and ERK1/2 pathways in HO-1 induction by YS-51. Taken together, we conclude that CO is, at least, responsible for the YS 51-mediated protective action of endothelial cells against oxidant stress via HO-1 gene induction, involving the activation of the PI3/Akt and ERK1/2 kinase pathways. Thus, YS 51 may be useful in oxidative stress-induced vascular disorders. PMID- 17719564 TI - Phosphodiesterase isozymes involved in regulation of HCO3- secretion in isolated mouse duodenum in vitro. AB - We examined the effects of various isozyme-selective PDE inhibitors on HCO(3)(-) secretion in the mouse duodenum in vitro and investigated which type(s) of phosphodiesterase (PDE) isozymes are involved in the response to PGE(2) and NO. The duodenal mucosa of male DDY mice was stripped of the muscle layer and mounted on an Ussing chamber, and HCO(3)(-) secretion was measured at pH 7.0 by a pH-stat method using 2mM HCl. Both PGE(2) and NOR-3 (NO donor) increased HCO(3)(-) secretion in the mouse duodenum in vitro, and the response to PGE(2) was inhibited by both EP3 and EP4 antagonists but not EP1 antagonist, while that to NOR-3 was inhibited by methylene blue. IBMX, a nonselective PDE inhibitor, significantly increased basal HCO(3)(-) secretion and potentiated the responses to both PGE(2) and NOR-3. Likewise, vinpocetine (PDE1 inhibitor) and cilostamide (PDE3 inhibitor) also increased the basal secretion at high doses and potentiated the HCO(3)(-) response to PGE(2) at doses that had no effect by themselves on the basal secretion. By contrast, the HCO(3)(-) stimulatory action of NOR-3 was significantly potentiated by vinpocetine but not cilostamide. Inhibitors of other PDE subtypes had no effect on the HCO(3)(-) secretion under basal or stimulated conditions. Both PDE1 and PDE3 mRNAs were expressed in the duodenal mucosa. These results suggested that PDE1 and PDE3 are involved in the regulation of duodenal HCO(3)(-) secretion and that the response to PGE(2) is associated with both PDE1 and PDE3, while the response to NO is mainly modulated by PDE1. PMID- 17719565 TI - N-acetylcysteine reduces extinction responding and induces enduring reductions in cue- and heroin-induced drug-seeking. AB - BACKGROUND: Previous studies show that the acute administration of N acetylcysteine (NAC) inhibits the desire for cocaine in addicts and cocaine seeking in animals. METHODS: Rats were trained to self-administer heroin, and the reinstatement model of drug seeking was used to determine whether chronic NAC treatment inhibited heroin-seeking. RESULTS: Daily NAC administration inhibited cue- and heroin-induced seeking. Moreover, repeated NAC administration during extinction training reduced extinction-responding and inhibited cue- and heroin induced reinstatement for up to 40 days after discontinuing daily NAC injection. CONCLUSIONS: These data show that daily NAC inhibits heroin-induced reinstatement and produces an enduring reduction in cue- and heroin-induced drug seeking for over 1 month after the last injection of NAC. Both the inhibitory effect of NAC on the reinstatement of heroin-seeking and the ability of NAC to reduce extinction-responding support clinical evaluation of repeated NAC administration to decrease in drug-seeking in heroin addicts. PMID- 17719566 TI - A functional magnetic resonance imaging investigation of uncertainty in adolescents with anxiety disorders. AB - BACKGROUND: Pediatric anxiety disorders, although highly prevalent, are understudied with little known about their pathophysiology. Intolerance of uncertainty (IU) is a trait associated with worry, a key characteristic of these disorders. Neural responses to uncertainty in healthy subjects involve the same frontal-limbic circuits that are hyper-responsive in pediatric anxiety. As such, the present study examines the relationship between IU and neural responses to uncertainty in anxious adolescents. METHODS: Sixteen adolescents (ages 13-17) diagnosed with generalized anxiety disorder and/or social phobia (ANX) and 13 non anxious control subjects completed a decision-making task while functional magnetic resonance imaging scans were acquired. RESULTS: The ANX group endorsed greater task-related anxiety and less certainty than control subjects on a post task questionnaire. Compared with control subjects, the ANX group did not demonstrate hyper-responsivity of brain regions as hypothesized. Across groups, IU was positively correlated with activity in several frontal and limbic regions. Further analyses identified subgroups within the ANX group: those with high IU activated frontal/limbic regions, whereas those with low IU and less anxiety during the task deactivated the same regions in response to uncertainty. CONCLUSIONS: Results substantiate the hypothesized link between IU and neural responses to uncertainty in some adolescents with anxiety disorders. Our findings, if replicated, suggest that trait measures, such as IU, can significantly improve our understanding of the neurobiological basis of pediatric anxiety disorders. PMID- 17719567 TI - Altered emotional interference processing in affective and cognitive-control brain circuitry in major depression. AB - BACKGROUND: Major depression is characterized by a negativity bias: an enhanced responsiveness to, and memory for, affectively negative stimuli. However, it is not yet clear whether this bias represents 1) impaired top-down cognitive control over affective responses, potentially linked to deficits in dorsolateral prefrontal cortex function; or 2) enhanced bottom-up responses to affectively laden stimuli that dysregulate cognitive control mechanisms, potentially linked to deficits in amygdala and anterior cingulate function. METHODS: We used an attentional interference task using emotional distracters to test for top-down versus bottom-up dysfunction in the interaction of cognitive-control circuitry and emotion-processing circuitry. A total of 27 patients with major depression and 24 control participants was tested. Event-related functional magnetic resonance imaging was carried out as participants directly attended to, or attempted to ignore, fear-related stimuli. RESULTS: Compared with control subjects, patients with depression showed an enhanced amygdala response to unattended fear-related stimuli (relative to unattended neutral). By contrast, control participants showed increased activity in right dorsolateral prefrontal cortex (Brodmann areas 46/9) when ignoring fear stimuli (relative to neutral), which the patients with depression did not show. In addition, the depressed participants failed to show evidence of error-related cognitive adjustments (increased activity in bilateral dorsolateral prefrontal cortex on posterror trials), but the control group did show them. CONCLUSIONS: These results suggest multiple sources of dysregulation in emotional and cognitive control circuitry in depression, implicating both top-down and bottom-up dysfunction. PMID- 17719569 TI - Role of Pterocarpus santalinus against mitochondrial dysfunction and membrane lipid changes induced by ulcerogens in rat gastric mucosa. AB - Free radicals produced by ulcerogenic agents affect the TCA cycle enzymes located in the outer membrane of the mitochondria. Upon induction with ulcerogens, peroxidation of membrane lipids bring about alterations in the mitochondrial enzyme activity. This indicates an increase in the permeability levels of the mitochondrial membrane. The ability of PSE to scavenge the reactive oxygen species results in restoration of activities of TCA cycle enzymes. NSAIDs interfere with the mitochondrial beta-oxidation of fatty acids in vitro and in vivo, resulting in uncoupling of mitochondrial oxidative phosphorylation process. This usually results in diminished cellular ATP production. The recovery of gastric mucosal barrier function through maintenance of energy metabolism results in maintenance of ATP levels, as observed in this study upon treatment with PSE. Membrane integrity altered by peroxidation is known to have a modified fatty acid composition, a disruption of permeability, a decrease in electrical resistance, and increase in flip-flopping between monolayers and inactivated cross-linked proteins. The severe depletion of arachidonic acid in ulcer induced groups was prevented upon treatment with PSE. The acid inhibitory property of the herbal extract enables the maintenance of GL activity upon treatment with PSE. The ability to prevent membrane peroxidation has been traced to the presence of active constituents in the PSE. In essence, PSE has been found to prevent mitochondrial dysfunction, provide mitochondrial cell integrity, through the maintenance of lipid bilayer by its ability to provide a hydrophobic character to the gastric mucosa, further indicating its ability to reverse the action of NSAIDs and mast cell degranulators in gastric mucosa. PMID- 17719568 TI - Subtractive hybridisation screen identifies genes regulated by glucose deprivation in human neuroblastoma cells. AB - Glucose is the major source of energy for the brain and inadequate glucose supply causes damage of neuronal cells. In this study we employed the human neuroblastoma cell line SH-SY5Y, as an in vitro model for neuronal cells, to identify genes regulated by glucose deprivation. Using subtractive hybridisation screen, validated by Northern analysis, we identify for the first time specific targets of the glucopenic response. These genes are involved in key cellular process including gene transcription, protein synthesis, mitochondrial metabolism, neuronal development, neuroprotection and neuronal apoptosis. Our findings suggest that the fate of neuronal cells undergoing glucose starvation relies on complex gene interactions. Modulation of the expression of these genes in vivo will enable determination of the precise role of each gene and possibly identify key elements and potential therapeutic targets of the glucopenic response. PMID- 17719570 TI - Your divided attention, please! The maintenance of multiple attentional control sets over distinct regions in space. AB - When non-informative peripheral cues precede a target defined by a specific feature, cues that share the critical feature will capture attention while cues that do not will be effectively ignored. We tested whether different attentional control sets can be simultaneously maintained over distinct regions of space. Participants were instructed to respond only to specific colored targets at specific locations. Most trials included non-predictive cues whose location and/or color were either congruent or incongruent with the spatial and/or color properties of the impending target. We observed contingent capture only for cues that were consistent with the attentional control set applied to that region of space. This is the first demonstration that separate attentional control sets can be simultaneously maintained at distinct spatial locations, with implications for the flexibility of endogenous control over automatic attentional orienting. PMID- 17719571 TI - Isothermal volume contours generated in a freezing gel by embedded cryo-needles with applications to cryo-surgery. AB - Three-dimensional numerical simulations of multi-cryo-needle surgery were performed with cryo-needle temperature variations taken from matched experimental data. The transient temperatures and frozen volumes generated by simultaneously operating up to three 1.47 mm OD cryo-needles embedded in a phase-changing gel simulating the properties of biological tissues, were studied. In all cases studied, the volumes enclosed by the "lethal", -40 degrees C isotherm, achieved most of their final size in the first few minutes of operation, thus obviating the need for long application times. After 30 min of application of the one-, two or three-cryo-needles, the ablation ratio attained 3%, 3-6% and 3-8%, respectively, depending on cryo-needle placement configurations. Synergistic effects of using multi-cryo-needles were reflected in the increased expansion of both the radial and axial locations of the isothermal contours. Within each number of cryo-needles used, however, the differences in these locations were rather small, and, as a general rule, tended to somewhat decrease with increasing the placement "density" of the cryo-needles. For each two- and three-cryo-needle application, there is a certain combination of placement configuration and application time that would produce the largest, temperature-specific, volume. As a general guideline, multiple cryo-needles should not be placed too close to each other in order to enhance their synergistic effect. Results of this study should be useful in the design of cryo-needle placement and operation protocols and in understanding the limitations of the freezing-ablation process. PMID- 17719572 TI - Dual function of Sox1 in telencephalic progenitor cells. AB - The transcription factor, Sox1 has been implicated in the maintenance of neural progenitor cell status, but accumulating evidence suggests that this is only part of its function. This study examined the role of Sox1 expression in proliferation, lineage commitment, and differentiation by telencephalic neural progenitor cells in vitro and in vivo, and further clarified the pattern of Sox1 expression in postnatal and adult mouse brain. Telencephalic neural progenitor cells isolated from Sox1 null embryos formed neurospheres normally, but were specifically deficient in neuronal differentiation. Conversely, overexpression of Sox1 in the embryonic telencephalon in vivo both expanded the progenitor pool and biased neural progenitor cells towards neuronal lineage commitment. Sox1 mRNA and protein were found to be persistently expressed in the postnatal and adult brain in both differentiated and neurogenic regions. Importantly, in differentiated regions Sox1 co-labeled only with neuronal markers. These observations, coupled with previous studies, suggest that Sox1 expression by early embryonic progenitor cells initially helps to maintain the cells in cell cycle, but that continued expression subsequently promotes neuronal lineage commitment. PMID- 17719573 TI - Effects of cyclooxygenase (COX) inhibition on memory impairment and hippocampal damage in the early period of cerebral hypoperfusion in rats. AB - Chronic cerebral hypoperfusion is related to neurological disorders and contributes to a cognitive decline. Its experimental model in rats is permanent, bilateral common carotid artery occlusion. The cyclooxygenase (COX) system plays a pivotal role in the evolution of ischemic brain damage. Several COX inhibitors have proved to be neuroprotective in stroke models. We set out to characterize the effects of COX inhibitors in rats with permanent cerebral hypoperfusion. Some of the animals were exposed to two-vessel occlusion (n=72), while the others served as sham-operated controls (n=54). This was followed by a 3-day post treatment with the nonselective COX inhibitor indomethacin (3 mg/kg) or with the selective COX-2 inhibitor NS-398 (15 mg/kg) or with the solvent. Some groups of the animals were sacrificed after 3 days, while the remainder were tested in the Morris watermaze for 5 days, and were sacrificed after 2 weeks. Neurons in the hippocampus were subjected to immunocytochemical labeling with cresyl violet, the dendrites with microtubule-associated protein-2, astrocytes with glial fibrillary acidic protein and microglia activation with OX-42 antibody. Two-vessel occlusion induced a learning impairment, mild neuronal damage, marked dendritic injury and moderate astrocytic reaction in the hippocampus. NS-398, but not indomethacin improved the survival rate and abolished the learning disability. However, both drugs increased the proportion of animals displaying neuronal damage. Glial markers revealed a time-dependent elevation in both the sham and the two-vessel occluded group, and were unaffected by the treatments. In summary, NS-398 prevented the hypoperfusion-induced memory impairment, but not by protecting the hippocampal neurons. PMID- 17719574 TI - The regulatory or phosphorylation domain of p120 catenin controls E-cadherin dynamics at the plasma membrane. AB - In contrast to growth factor-stimulated tyrosine phosphorylation of p120, its relatively constitutive serine/threonine phosphorylation is not well understood. Here we examined the role of serine/threonine phosphorylation of p120 in cadherin function. Expression of cadherins in cadherin-null cells converted them to an epithelial phenotype, induced p120 phosphorylation and localized it to sites of cell contact. Detergent solubility and immunofluorescence confirmed that phosphorylated p120 was at the plasma membrane. E-cadherin constructs incapable of traveling to the plasma membrane did not induce serine/threonine phosphorylation of p120, nor did cadherins constructs incapable of binding p120. However, an E-cadherin cytoplasmic domain construct artificially targeted to the plasma membrane did induce serine/threonine phosphorylation of p120, suggesting phosphorylation occurs independently of signals from cadherin dimerization and trafficking through the ER/Golgi. Solubility assays following calcium switch showed that p120 isoform 3A was more effective at stabilizing E-cadherin at the plasma membrane relative to isoform 4A. Since the major phosphorylation domain of p120 is included in isoform 3A but not 4A, we tested p120 mutated in the known phosphorylation sites in this domain and found that it was even less effective at stabilizing E-cadherin. These data suggest that serine/threonine phosphorylation of p120 influences the dynamics of E-cadherin in junctions. PMID- 17719576 TI - Antibody array characterization of inflammatory mediators in allergic and normal tears in the open and closed eye environments. AB - To evaluate the use of stationary phase protein array technology for tear analysis and to characterize the distribution of inflammatory mediators in normal and allergic tears in the open and closed eye states. Microcapillary tube collected Open (OTF) and closed eye tear fluid (CTF) samples from normals (N), from individuals with various active chronic ocular and other allergies (CA), as well as from an individual subsequent to unilateral induction of an acute allergic conjunctivitis were assayed using membrane arrays that were optimized to allow the detection of GM-CSF, ILs-1 alpha, 1 beta, 2-10, 12-13, INF gamma, MCP-1 and TNFalpha in clinical size samples. The protocol of a micro-well plate array specific for ILs-2, 4, 5, 8, 10, 12, 13, TNFalpha and INF gamma was modified to minimize the impact of tear matrix effects. This was used to carry out parallel analysis on selected samples. By optimizing the protocol as well as the composition of a membrane array it proved possible to significantly increase the signal-to-noise ratio and sensitivity of assay allowing for the detection of some inflammatory mediators into the sub-picogram range. This provided sufficient sensitivity to allow the assay of clinically obtainable size samples. Analysis revealed that OTF from most Ns contained a high level of IL-8 and faint signals if any for the other probed proteins. In contrast, OTF samples from most CA individuals with and without ocular symptoms exhibited to varying degrees detectable levels of most of the other probed entities. The difference between normal and pathological tears and the levels of signals became far more pronounced in the CTF compared to the OTF samples. Use of the micro-well plate assay kit without modification revealed two tear matrix effects that profoundly impact the ability to obtain meaningful ELISA data. Modifying the assay protocol reduces but does not eliminate these artifacts making it possible to approximate the concentration of many of the probed entities. The obtained data is consistent using both methodologies revealing elevated levels of IL-8 and other cytokines in approximately 60% of the OTF samples from the CA population. Other than a modest increase in IL-8, no change could be observed in the profile of OTF after induction of an acute allergic reaction. PMID- 17719575 TI - Promoter-independent regulation of vimentin expression in mammary epithelial cells by val(12)ras and TGFbeta. AB - The 1,029 series of mammary epithelial cell lines (D6, GP+E, r3 and r3T) are progressively more transformed: the latter two by val(12)ras. These cell lines respond to TGFbeta by undergoing early events of epithelial-mesenchymal transition (EMT), including morphological changes and redistribution of E cadherin. Tumors formed by r3T cells in the choroid of the eye express vimentin, a late marker of EMT, possibly in response to TGFbeta. In vitro, vimentin expression is induced in all the cell lines by TGFbeta treatment, whereas cytokeratin expression is only slightly affected. Surprisingly, ras transformation results in a 10-fold suppression of vimentin expression. Neither suppression of vimentin by ras transformation nor induction by TGFbeta is mediated by the vimentin promoter in r3T cells. In transient transfection assays, several human vimentin promoter constructs are more active in the low-expressing r3T cell line than in the vimentin-expressing mesenchymal cell line NIH3T3. In the r3T cells, there is no effect of TGFbeta treatment for 9 days on the activity of either promoter. Azacytidine treatment does not affect vimentin expression in either NIH3T3 or r3T, suggesting that promoter methylation is not the mechanism of suppression by ras. Finally, the half-life of the vimentin mRNA is similar in both the r3T cells and NIH3T3 cells. We conclude that the suppression of vimentin expression by ras, and the relief of this suppression by TGFbeta, occurs in a promoter-independent fashion, possibly through sequences in the first or second intron. PMID- 17719578 TI - Leishmania chagasi: cytotoxic effect of infected macrophages on parenchymal liver cells. AB - Leishmania (Leishmania) chagasi, the ethiological agent of New World visceral leishmaniasis, causes morphological and functional injury to the liver. To investigate the role of macrophage-released leishmanicidal factors in hepatocyte damage, we used a co-culture model of hepatocytes and L. chagasi promastigote infected peritoneal macrophages obtained from C57BL/6 or BALB/c mice. C57BL/6 macrophages killed intracellular parasites more efficiently than BALB/c macrophages, leading to higher number of intracellular amastigotes in the BALB/c culture during the entire course of infection. Early TNF-alpha production led to macrophages activation resulting in parasite growth control. Hepatic transaminases and lactate dehydrogenase were present at high levels in the supernatants of both co-cultures; concurrently, parasites were eliminated from infected macrophages. Nitric oxide production was higher in C57BL/6 co-cultures than in BALB/c co-cultures. Inhibitors of the oxidative burst and secreted proteinases protected hepatocytes against toxicity, and treatment with an inducible nitric oxide synthase inhibitor fully impeded the enzyme release. Our data suggest that the intracellular cytotoxic effects elicited by macrophages for parasite destruction are directly associated with hepatocyte damage, and that nitric oxide plays a pivotal role in this phenomenon. PMID- 17719577 TI - Transduced Schwann cells promote axon growth and myelination after spinal cord injury. AB - We sought to directly compare growth and myelination of local and supraspinal axons by implanting into the injured spinal cord Schwann cells (SCs) transduced ex vivo with adenoviral (AdV) or lentiviral (LV) vectors encoding a bifunctional neurotrophin molecule (D15A). D15A mimics actions of both neurotrophin-3 and brain-derived neurotrophic factor. Transduced SCs were injected into the injury center 1 week after a moderate thoracic (T8) adult rat spinal cord contusion. D15A expression and bioactivity in vitro; D15A levels in vivo; and graft volume, SC number, implant axon number and cortico-, reticulo-, raphe-, coerulo-spinal and sensory axon growth were determined for both types of vectors employed to transduce SCs. ELISAs revealed that D15A-secreting SC implants contained significantly higher levels of neurotrophin than non-transduced SC and AdV/GFP and LV/GFP SC controls early after implantation. At 6 weeks post-implantation, D15A-secreting SC grafts exhibited 5-fold increases in graft volume, SC number and myelinated axon counts and a 3-fold increase in myelinated to unmyelinated (ensheathed) axon ratios. The total number of axons within grafts of LV/GFP/D15A SCs was estimated to be over 70,000. Also 5-HT, DbetaH, and CGRP axon length was increased up to 5-fold within D15A grafts. In sum, despite qualitative differences using the two vectors, increased neurotrophin secretion by the implanted D15A SCs led to the presence of a significantly increased number of axons in the contusion site. These results demonstrate the therapeutic potential for utilizing neurotrophin-transduced SCs to repair the injured spinal cord. PMID- 17719579 TI - Tumor necrosis factor-alpha exerts pro-myogenic action in C2C12 myoblasts via sphingosine kinase/S1P2 signaling. AB - In this study, we report that low doses of tumor necrosis factor-alpha (TNFalpha) promote myogenesis in C2C12 myoblasts. Moreover, the cytokine increased sphingosine kinase (SphK) activity and induced SphK1 translocation to membranes. The inhibition of SphK functionality by various approaches abrogated the pro myogenic effect of TNFalpha. Moreover, silencing of S1P(2) impaired the positive action of TNFalpha on myogenesis. These results represent the first evidence that SphK/S1P(2) axis is required for the regulation of myogenesis by TNFalpha. In view of the physiological role of TNFalpha in muscle regeneration, the present finding reinforces the notion that SphK/S1P(2) signaling is critically implicated in myogenesis. PMID- 17719580 TI - Human manganese superoxide dismutase suppresses HER2/neu-mediated breast cancer malignancy. AB - The up-regulation of HER2/neu is associated with human malignancies and is a useful target for developing anticancer drugs. Overexpression of human manganese superoxide dismutase (MnSOD) has been demonstrated to effectively suppress various carcinoma cells, including breast carcinomas, in vitro and in vivo. This study demonstrates that MnSOD effectively suppresses HER2/neu oncogene expression at the transcriptional level. Additionally, stable transfection was used and the MnSOD-transfected human breast cancer clones were found to be able to down regulate the endogenous production of p185(HER2/neu). Furthermore, the MnSOD overexpressing stable transfectants exhibited reduced soft-agarose colony-forming ability and metastatic properties, unlike control cell lines. These data suggest that MnSOD may be useful in treating HER2/neu-mediated human breast tumor malignancy. PMID- 17719581 TI - Molecular determinants for FMN-binding in Desulfovibrio gigas flavoredoxin. AB - Flavoredoxin participates in Desulfovibrio gigas thiosulfate reduction pathway. Its 3-dimensional model was generated allowing the oxidized riboflavin-5' phosphate (FMN) site to be predicted. Residues likely to be involved in FMN binding were identified (N29, W35, T56, K92, H131 and F164) and mutated to alanine. Fluorescence titration with apoprotein showed that FMN is strongly bound in the wild-type protein. Comparison of K(d) values for mutants suggests that interactions with the phosphate group of FMN, contribute more to binding than the interactions with the isoalloxazine ring. The redox potential of bound FMN determined for wild-type and mutants revealed shifts to less negative values. These findings were correlated with the protein structure in order to contribute to a better understanding of the structure-function relationships in flavoredoxin. PMID- 17719582 TI - Myotonic dystrophy CTG repeat expansion alters Ca2+ channel functional expression in PC12 cells. AB - We previously reported that expression of myotonic dystrophy (DM1) expanded CUG repeats impedes NGF-induced differentiation in a PC12 clone (CTG90 cells). Here, we present evidence for changes in the fractional contribution of distinct voltage-gated Ca(2+) channels, key elements in neurotrophin-promoted differentiation, to the total Ca(2+) current in the CTG90 cells. Patch-clamp recordings showed that the relative proportion of pharmacologically isolated Ca(2+) channel types differed between control and CTG90 cells. Particularly, the functional expression of N-type channels was significantly reduced. Though quantitative real-time RT-PCR revealed that transcripts for the pore-forming subunit encoding the N-type channels remained unchanged, the protein level analyzed by semi-quantitative Western blotting was down-regulated in the CTG90 cells. These data suggest modifications in the processing of N-type Ca(2+) channels in PC12 cells expressing the DM1 mutation. PMID- 17719583 TI - The reactivation of DnaA(L366K) requires less acidic phospholipids supporting their role in the initiation of chromosome replication in Escherichia coli. AB - DnaA(L366K), in concert with a wild-type DnaA (wtDnaA) protein, restores the growth of Escherichia coli cells arrested in the absence of adequate levels of cellular acidic phospholipids. In vitro and in vivo studies showed that DnaA(L366K) alone does not induce the initiation of replication, and wtDnaA must also be present. Hitherto the different behavior of wt and mutant DnaA were not understood. We now demonstrate that this mutant may be activated at significantly lower concentrations of acidic phospholipids than the wild-type protein, and this may explain the observed growth restoration in vivo. PMID- 17719584 TI - Lysophosphatidylethanolamine stimulates chemotactic migration and cellular invasion in SK-OV3 human ovarian cancer cells: involvement of pertussis toxin sensitive G-protein coupled receptor. AB - We investigated whether lysophosphatidylethanolamine (LPE) modulates cellular signaling in different cell types. SK-OV3 ovarian cancer cells and OVCAR-3 ovarian cancer cells were responsive to LPE. LPE-stimulated intracellular calcium concentration ([Ca(2+)](i)) increase was inhibited by U-73122, suggesting that LPE stimulates calcium signaling via phospholipase C activation. Moreover, pertussis toxin (PTX) almost completely inhibited [Ca(2+)](i) increase by LPE, indicating the involvement of PTX-sensitive G-proteins. Furthermore, we found that LPE stimulated chemotactic migration and cellular invasion in SK-OV3 ovarian cancer cells. We examined the role of lysophosphatidic acid receptors on LPE stimulated cellular responses using HepG2 cells transfected with different LPA receptors, and found that LPE failed to stimulate nuclear factor kappa B-driven luciferase. We suggest that LPE stimulates a membrane bound receptor, different from well known LPA receptors, resulting in chemotactic migration and cellular invasion in SK-OV3 ovarian cancer cells. PMID- 17719585 TI - Gastric polyposis in familial juvenile polyposis. PMID- 17719586 TI - Ascaris-induced acute pancreatitis treated endoscopically. PMID- 17719587 TI - Malignant insulinoma: a rare presentation of a rare tumor. PMID- 17719588 TI - Intrahepatic trifistula causing bilhemia and hemobilia resulting from transjugular liver biopsy in the setting of biliary tract obstruction (with video). PMID- 17719589 TI - Automation of the temperature elevation test in transformers with insulating oil. AB - The automation of the temperature elevation test is outlined here for both the oil temperature elevation and the determination of the winding temperature elevation. While automating this test it is necessary to use four thermometers, one three-phase wattmeter, a motorized voltage variator and a Kelvin bridge to measure the resistance. All the equipments must communicate with a microcomputer, which will have the test program implemented. The system to be outlined here was initially implemented in the laboratory and, due to the good results achieved, is already in use in some transformer manufacturing plants. PMID- 17719591 TI - Application of ceramic/carbon composite as a novel coating for solid-phase microextraction. AB - A ceramic/carbon composite was developed and applied as a novel coating for solid phase microextraction (SPME). The ceramic/carbon coating exhibited several good properties for SPME, such as high extraction quantities and enhanced thermal and organic solvent stability. Under scanning electron microscopy (SEM), the tightly attached coating layer on stainless steel wire revealed excellent mechanical characteristics. Single fiber and fiber-to-fiber reproducibility were less than 6.9 and 9.5%, respectively. The effects of extraction and desorption parameters such as extraction time, stirring rate, ionic strength, and desorption temperature and desorption time on the extraction/desorption efficiency were investigated and optimized. Coupled to gas chromatography with a flame thermionic detector, the optimized SPME method was applied to the analysis of organophosphorus pesticides (OPPs) in aqueous samples. The calibration curves were linear from 0.05 to 200 ng mL(-1) for fenchlorphos, pirimiphos-methyl, chlorpyrifos, ethion and from 0.2 to 200 ng mL(-1) for quinalphos, and the limits of detection were between 5.2 and 34.6 ng L(-1). The recovery of the OPPs spiked in real water samples at 5 ng mL(-1) ranged from 86.2 to 103.4% and the relative standard deviations were less than 8.5%. PMID- 17719592 TI - Comparative study of the performance of columns packed with several new fine silica particles. Would the external roughness of the particles affect column properties? AB - We measured and compared the characteristics and performance of columns packed with particles of five different C(18)-bonded silica, 3 and 5 microm Luna, 3 microm Atlantis, 3.5 microm Zorbax, and 2.7 microm Halo. The average particle size of each material was derived from the SEM pictures of 200 individual particles. These pictures contrast the irregular morphology of the external surface of the Zorbax and Halo particles and the smooth surface of the Luna and Atlantis particles. In a wide range of mobile phase velocities (from 0.010 to 3 mL/min) and at ambient temperature, we measured the first and second central moments of the peaks of naphthalene, insulin, and bovine serum albumin (BSA). These moments were corrected for the contributions of the extra-column volumes to calculate the reduced HETPs. The C-terms of naphthalene and insulin are largest for the Halo and Zorbax materials and the A-term smallest for the Halo-packed column. The Halo column performs the best for the low molecular weight compound naphthalene (minimum reduced HETP, 1.4) but is not as good as the Atlantis or Luna columns for the large molecular weight compound insulin. The Zorbax column is the least efficient column because of its large C-term. The lowest sample diffusivity through these particles, alone, does not account for the results. It is most likely that the roughness of the external surface of the Halo and Zorbax particles limit the performance of these columns at high flow rates generating an unusually high film mass transfer resistance. PMID- 17719593 TI - Could linear solvation energy relationships give insights into chiral recognition mechanisms? 2. Characterization of macrocyclic glycopeptide stationary phases. AB - Five parameter linear solvation energy relationships (LSER) are known to have little or no shape recognition ability. However, it is proposed to use LSER studies to get insights into chiral recognition mechanisms. Since the two enantiomers have exactly the same five A-V solute descriptors being still separated by chiral stationary phases (CSPs), it can be considered that they form two different transient diastereoisomers with the CSP. It is then possible to perform LSER studies on the enantioselectivity factors taken as the two enantiomer retention factor ratios. In a first step, the five a-v system parameters of four CSPs of the macrocyclic glycopeptide types were determined using a set of test solutes with known A-V descriptors, both in the reversed phase and the normal phase modes. In a second step, the A-V descriptors of 18 enantiomeric pairs were tentatively established using five achiral columns with known a-v parameters. This was successful for the five molecular enantiomers only. It was found that the predicted retention factor for the molecular enantiomers separated on a given CSP corresponded either to retention factor of the first experimentally eluted enantiomer or to the second one or to none of them. Using the enantioselectivity factors it was possible to obtain the Deltaa Deltav parameters corresponding to the difference in CSP properties seen by the two enantiomers. For the five molecular enantiomeric pairs in the reversed phase mode with a teicoplanin CSP, it was found that there was an elevated contribution by the e coefficient that we interpret as a possible interaction between surface charges on the teicoplanin CSP and solute induced dipoles. Steric effects, seen on the v parameter, are second in magnitude followed by H-bond and polar interactions. Only one solute could be studied in the normal phase mode showing a different mechanism with polar and steric major interactions. PMID- 17719594 TI - Octanol/water partitioning simulation by reversed-phase high performance liquid chromatography for structurally diverse acidic drugs: Effect of n-octanol as mobile phase additive. AB - The role of n-octanol as mobile phase additive for the lipophilicity assessment of 45 structurally diverse acidic drugs both at neutral (pH 2.5) and ionized form (pH 7.4) was investigated. Extrapolated retention factors logk(w) were determined on a BDS C18 column using methanol as organic modifier and different amounts of n octanol as mobile phase additive. For more polar compounds, the effect of n octanol in retention was found to decrease as their lipophilicity increased. In the case of carboxylic acids and oxicams, the differentiation in retention, in presence and absence of n-octanol, could be further attributed to the attenuation of polar interactions, concerning mainly hydrogen bonding. At pH 2.5, the use of n-octanol saturated buffer, without further addition of n-octanol in the mobile phase, led to 1:1 correlation with logP. At physiological pH, 1:1 correlation was obtained between logD(7.4) and logk(w)(oct) indices upon addition of 0.25% n octanol, in the case of weak acids. For strongly ionized compounds, a good correlation was also established under the same conditions. The corresponding equation, however, possessed a large negative intercept and a slope lower than unity. PMID- 17719595 TI - Ultrasonic assisted protein enzymatic digestion for fast protein identification by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Sonoreactor versus ultrasonic probe. AB - Two different ultrasonic energy sources, the sonoreactor and the ultrasonic probe, are compared for enzymatic digestion of proteins for protein identification by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) using the peptide mass fingerprint (PMF) procedure. Variables such as (i) trypsin/protein ratio; (ii) sonication time; (iii) ultrasound amplitude; and (iv) protein concentration are studied and compared. As a general rule, the trypsin/protein ratio and the minimum protein concentration successfully digested are similar with both ultrasonic energy sources. Results showed that the time needed to digest proteins was shorter with the ultrasonic probe, 60s versus 120s, for the same amplitude of sonication, 50%. However, lower standard deviations and cleaner MALDI-TOF-MS spectra were obtained with the sonoreactor. In addition, the sonoreactor device provided higher sample throughput (6 samples for the sonoreactor versus 1 sample for the ultrasonic probe) and easier sample handling for lower sample volumes (25 microl). Finally, a comparison of both methodologies for the specific identification of the adenylylsulphate reductase alfa subunit from a complex protein mixture from Desulfovibrio desulfuricans ATCC 27774 was done as a proof of the procedure. PMID- 17719596 TI - A general method to synthesis of amphiphilic colloidal nanoparticles of CdS and noble metals. AB - Amphiphilic colloids of CdS and noble metal nanoparticles, which can be dispersed both in water and organic solvents such as ethanol, N,N-dimethylformamide, chloroform, and toluene, are studied. The amphiphilic colloidal nanoparticles are synthesized by grafting the amphiphilic and thermoresponsive polymer of thiol terminated poly(N-isopropylacrylamide) to CdS and noble metal nanoparticles. The size and morphology of the PNIPAM-grafted colloidal nanoparticles of CdS@PNIPAM can be tuned by changing the molar ratio of PNIPAM/CdS. The size of CdS@PNIPAM nanoparticles slightly decreases first from 5.5 to 4.4 nm then slightly increases from 4.4 to 6.1 nm with the decrease in the molar ratio from 1/1 to 1/10. Spherical nanoparticles of CdS@PNIPAM are synthesized at a higher molar ratio and worm-like nanoparticles are obtained at a lower molar ratio. The resultant PNIPAM grafted colloidal nanoparticles of CdS@PNIPAM, Au@PNIPAM, Pd@PNIPAM, and Ag@PNIPAM are thermoresponsive in water and show a cloud-point temperature at about 32.5 degrees C. PMID- 17719597 TI - Face preferred deposition of gold nanoparticles on alpha-cyclodextrin/octanethiol inclusion compound. AB - The preferred deposition of gold nanoparticles (Au NPs) onto microcrystal faces of alpha-cyclodextin/octanethiol inclusion compound was obtained. The immobilization of Au NPs is caused by the spatial replacing of the citrate shell of the NPs by the free dangling SH groups of the guest molecule. PMID- 17719598 TI - Modulating properties of aqueous sodium dodecyl sulfate by adding hydrophobic ionic liquid. AB - Altering and modifying important physicochemical properties of aqueous surfactant solutions is highly desirable as far as potential applications of such systems are concerned. Changes in the properties of aqueous solutions of a common anionic surfactant sodium dodecyl sulfate (SDS) are assessed in the presence of a common and popular 'hydrophobic' ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate (bmimPF(6)). Upon addition of up to approximately 0.10 wt% bmimPF(6), a dramatic decrease in critical micelle concentration (cmc) is accompanied by an increase in the degree of counterion dissociation (alpha) and micellar aggregation number (N(agg)) indicating micellar growth. However, in the range 0.10 wt% < or = bmimPF(6) 2.00 wt%, relatively gradual decrease in alpha and N(agg) is observed along with no change in cmc. Significantly decreased microfluidity of the aqueous SDS solutions on addition of bmimPF(6) is indicated by a fluorescence microviscosity probe 1,3-bis-(1-pyrenyl)propane which suggests partitioning of bmimPF(6) into the SDS micellar phase. Behavior of solvatochromic fluorescence probes, pyrene, pyrene-1-carboxaldehyde, and 2-(p toluidino)naphthalene-6-sulfonate, confirms interaction, and possible complexation, between IL bmimPF(6) and anionic micellar surface. Increased solubility of bmimPF(6) with increasing SDS concentration further confirms SDS bmimPF(6) interactions. Presence of strong electrostatic attraction between bmim(+) and anionic micellar surface is proposed to be the most dominant reason for these observations. All-in-all, unique role of a hydrophobic ionic liquid bmimPF(6) in modifying the properties of aqueous anionic sodium dodecyl sulfate is demonstrated. PMID- 17719599 TI - Diffusioosmotic flows in slit nanochannels. AB - Diffusioosmotic flows of electrolyte solutions in slit nanochannels with homogeneous surface charges induced by electrolyte concentration gradients in the absence of externally applied pressure gradients and potential differences are investigated theoretically. A continuum mathematical model consisting of the strongly coupled Nernst-Planck equations for the ionic species' concentrations, the Poisson equation for the electric potential in the electrolyte solution, and the Navier-Stokes equations for the flow field is numerically solved simultaneously. The induced diffusioosmotic flow through the nanochannel is computed as functions of the externally imposed concentration gradient, the concentration of the electrolyte solution, and the surface charge density along the walls of the nanochannel. With the externally applied electrolyte concentration gradient, a strongly spatially dependent electric field and pressure gradient are induced within the nanochannel that, in turn, generate a spatially dependent diffusioosmotic flow. The diffusioosmotic flow is opposite to the applied concentration gradient for a relatively low bulk electrolyte concentration. However, the electrolyte solution flows from one end of the nanochannel with a higher electrolyte concentration to the other end with a lower electrolyte concentration when the bulk electrolyte concentration is relatively high. There is an optimal concentration gradient under which the flow rate attains the maximum. The induced flow is enhanced with the increase in the fixed surface charge along the wall of the nanochannel for a relatively low bulk electrolyte concentration. PMID- 17719600 TI - Removal of lead from aqueous solutions using Cassia grandis seed gum-graft poly(methylmethacrylate). AB - Using persulfate/ascorbic acid redox system, a series of Cassia grandis seed gum graft-poly(methylmethacrylate) samples were synthesized. The copolymer samples were evaluated for lead(II) removal from the aqueous solutions where the sorption capacities were found proportional to the grafting extent. The conditions for the sorption were optimized using copolymer sample of highest percent grafting. The sorption was found pH and concentration dependent, pH 2.0 being the optimum value. Adsorption of lead by the grafted seed gum followed a pseudo-second-order kinetics with a rate constant of 4.64 x 10(-5) g/mg/min. The equilibrium data followed the Langmuir isotherm model with maximum sorption capacity of 126.58 mg/g. The influence of electrolytes NaCl, Na(2)SO(4) on lead uptake was also studied. Desorption with 2 N HCl could elute 76% of the lead ions from the lead loaded copolymer. The regeneration experiments revealed that the copolymer could be successfully reused for at least four cycles though there was a successive loss in lead sorption capacity with every cycle. The adsorbent was also evaluated for Pb(II) removal from battery waste-water containing 2166 mg/L Pb(II). From 1000 times diluted waste water, 86.1% Pb(II) could be removed using 0.05 g/20 ml adsorbent dose, while 0.5 g/20 ml adsorbent dose was capable of removing 60.29% Pb from 10 times diluted waste water. Optimum Pb(II) binding under highly acidic conditions indicated that there was a significant contribution of nonelectrostatic interactions in the adsorption process. A possible mechanism for the adsorption has been discussed. PMID- 17719601 TI - Interaction between lysozyme and poly(acrylic acid) microgels. AB - The interaction between lysozyme and oppositely charged poly(acrylic acid) microgels was investigated by micromanipulator-assisted light microscopy, confocal microscopy and circular dichroism. Lysozyme uptake and distribution within the microgel particles, and its effect on microgel deswelling, was studied regarding effects of pH, ionic strength and lysozyme concentration. For a range of conditions, lysozyme distributes nonuniformly within the microgels, forming a lysozyme/microgel shell in the outer parts of the microgel. This shell formation is associated both with increased lysozyme loading to the microgels and with increased lysozyme-induced microgel deswelling. At high microgel charge density, the shell formation displays nonmonotonic ionic strength dependence. The shells formed are characterized by a net positive charge, and by relatively fast exchange of lysozyme between shell and solution, although the exchange kinetics decreases strongly with decreasing ionic strength. At conditions of slower exchange kinetics, the shells are characterized by an effective pore size of less than about 4 nm. PMID- 17719602 TI - A sensitive assay for the quantification of integrin-mediated adhesiveness of human stem cells and leukocyte subpopulations in whole blood. AB - Adhesion of leukocytes is an early step in the formation of adaptive or innate immunity. In chronic inflammatory pathologies like atherosclerosis, regulation of adhesiveness is pivotal for the accumulation of leukocytes within the vessel wall. Therefore, the quantification of adhesion is crucial for the understanding and monitoring of immune responses in patients. However, so far, functional analysis of leukocyte adhesion has been time consuming and required prior purification of cell populations from peripheral blood. This reduced the number of samples and cell populations that could be analysed from limited patient material. Here, we introduce a novel method involving rapid quantification of integrin-mediated leukocyte adhesion in human whole blood using flow cytometry. The quantification relies on soluble multivalent immunocomplexes and is thus called "ligand-complex-based adhesion assay" (LC-AA). LC-AA evaluates both integrin affinity and avidity in T-cells, NK-cells and monocytes from as little as 20 mul of whole blood. In marked contrast to T-cells and NK-cells, unstimulated monocytes show non-blockable background binding of the complexes. Therefore, for this subset only, the stimulation-induced integrin activation is measurable. With the LC-AA, for the first time, measurement of adhesiveness of extremely rare cell populations like CD34+ peripheral blood stem cells can be assessed in the absence of prior purification steps. Finally, the small blood volumes needed for adhesion analysis with the LC-AA allow the evaluation of multiple cell subpopulations in large sample collectives, e.g. required in clinical studies. PMID- 17719603 TI - A novel technique for NOD2/CARD15 genotyping using PCR-SSP. AB - The Nucleotide-binding Oligomerisation Domain (NOD) 2 protein is encoded by the Caspase Recruitment Domain (CARD) 15 gene and has a critical role in innate immunity. Recent studies have implicated Single Nucleotide Polymorphisms (SNPs) of the NOD2/CARD15 gene with the onset of several Inflammatory Bowel Disorders (Crohn's Disease, Blau syndrome) and the progression of several malignant diseases. The identification of SNPs in the genotypes of donor and recipient pairs prior to haematopoietic stem cell transplantation have also been shown to predict for a worse outcome, specifically causing increases in the incidence and severity of acute Graft-versus-Host disease, disease relapse and mortality. In light of these widespread areas of interest, we have developed a Polymerase Chain Reaction assay using Sequence Specific Primers (PCR-SSP) to identify the three SNPs that have been implicated, (SNPs 8, 12 and 13). The assay has proven to be a rapid and accurate method of performing NOD2/CARD15 genotyping when compared to other techniques described to date. PMID- 17719604 TI - Susceptibility and immune response of Deroceras reticulatum, Milax gagates and Limax pseudoflavus exposed to the slug parasitic nematode Phasmarhabditis hermaphrodita. AB - We exposed three slug species (Deroceras reticulatum (Muller), Milax gagates (Draparnaud) and Limax pseudoflavus L.) to the parasitic nematode Phasmarhabditis hermaphrodita Schneider. P. hermaphrodita was able to cause mortality and feeding inhibition to both D. reticulatum and M. gagates but did not negatively affect L. pseudoflavus. On dissection of surviving L. pseudoflavus large numbers of P. hermaphrodita were found encapsulated in the shell of the slug. We found that by increasing shell size, the slug was able to trap invading nematodes, which could be an immune response to P. hermaphrodita invasion. This is the first report of a slug defense mechanism to inhibit P. hermaphrodita. PMID- 17719605 TI - Evidence for induced fit in bacterial RNase P RNA-mediated cleavage. AB - RNase P with its catalytic RNA subunit is involved in the processing of a number of RNA precursors with different structures. However, precursor tRNAs are the most abundant substrates for RNase P. Available data suggest that a tRNA is folded into its characteristic structure already at the precursor state and that RNase P recognizes this structure. The tRNA D-/T-loop domain (TSL-region) is suggested to interact with the specificity domain of RNase P RNA while residues in the catalytic domain interact with the cleavage site. Here, we have studied the consequences of a productive interaction between the TSL-region and its binding site (TBS) in the specificity domain using tRNA precursors and various hairpin-loop model substrates. The different substrates were analyzed with respect to cleavage site recognition, ground-state binding, cleavage as a function of the concentration of Mg(2+) and the rate of cleavage under conditions where chemistry is suggested to be rate limiting using wild-type Escherichia coli RNase P RNA, M1 RNA, and M1 RNA variants with structural changes in the TBS region. On the basis of our data, we conclude that a productive TSL/TBS interaction results in a conformational change in the M1 RNA substrate complex that has an effect on catalysis. Moreover, it is likely that this conformational change comprises positioning of chemical groups (and Mg(2+)) at and in the vicinity of the cleavage site. Hence, our findings are consistent with an induced fit mechanism in RNase P RNA-mediated cleavage. PMID- 17719607 TI - Preservation of brainstem neurophysiological function in hydranencephaly. AB - The preservation of central neurophysiological function was assessed in a 32-year old woman with hydranencephaly using brainstem auditory evoked responses (BAER), auditory middle latency responses (MLR), cortical auditory evoked responses (CER), strobe electroretinograms (ERG), strobe-flash visual evoked responses (VER) and median and tibial nerve somatosensory evoked responses (SER). The BAER to the right ear stimulation revealed wave peaks I through VII with normal thresholds, morphology and latencies, while the BAER in the left ear was abnormal. The auditory MLR and CER were absent. Grossly normal strobe ERGs were acquired bilaterally with peak waves at 20 and 50 ms. Strobe VERs were poorly defined and abnormal bilaterally. Left and right median nerve SER revealed significant conduction defects in the large fiber sensory system caudal to the thalamus, above the lower pontine level. Bilateral tibial nerve stimulation revealed normal knee popliteal fossa potentials, but distinct conduction defects in the large fiber sensory system rostral to the lower spinal cord. Brainstem electrophysiological measures revealed functional auditory afferent tracts and nuclei, in the absence of cortical influence, suggesting intact unilateral auditory function, which would support clinical observations of behavioral auditory responses in hydranencephaly. PMID- 17719606 TI - Dynamic structure of retinylidene ligand of rhodopsin probed by molecular simulations. AB - Rhodopsin is currently the only available atomic-resolution template for understanding biological functions of the G protein-coupled receptor (GPCR) family. The structural basis for the phenomenal dark state stability of 11-cis retinal bound to rhodopsin and its ultrafast photoreaction are active topics of research. In particular, the beta-ionone ring of the retinylidene inverse agonist is crucial for the activation mechanism. We analyzed a total of 23 independent, 100 ns all-atom molecular dynamics simulations of rhodopsin embedded in a lipid bilayer in the microcanonical (N,V,E) ensemble. Analysis of intramolecular fluctuations predicts hydrogen-out-of-plane (HOOP) wagging modes of retinal consistent with those found in Raman vibrational spectroscopy. We show that sampling and ergodicity of the ensemble of simulations are crucial for determining the distribution of conformers of retinal bound to rhodopsin. The polyene chain is rigidly locked into a single, twisted conformation, consistent with the function of retinal as an inverse agonist in the dark state. Most surprisingly, the beta-ionone ring is mobile within its binding pocket; interactions are non-specific and the cavity is sufficiently large to enable structural heterogeneity. We find that retinal occupies two distinct conformations in the dark state, contrary to most previous assumptions. The beta ionone ring can rotate relative to the polyene chain, thereby populating both positively and negatively twisted 6-s-cis enantiomers. This result, while unexpected, strongly agrees with experimental solid-state (2)H NMR spectra. Correlation analysis identifies the residues most critical to controlling mobility of retinal; we find that Trp265 moves away from the ionone ring prior to any conformational transition. Our findings reinforce how molecular dynamics simulations can challenge conventional assumptions for interpreting experimental data, especially where existing models neglect conformational fluctuations. PMID- 17719608 TI - Host-parasite interactions between the local and the mean-field: how and when does spatial population structure matter? AB - The assumption that populations are completely mixed is reasonable for many populations, but there is likely to be some degree of local interaction whether spatially or socially in many systems. An important question is therefore how strong these local interactions need to be before there are significant effects on the dynamics of the system. Here, our approach is to use a multi-scale pair approximation model to move between completely local and completely mixed host parasite interactions. We show that systems dominated by near neighbour effects have less persistence of disease, and a greater possibility of parasite driven extinction and limit cycles. Furthermore this reduction in persistence occurs over a wide range of infection scales and is still significant in predominantly mixed host populations. Deterministic extinctions are only likely in highly spatial SI systems while oscillations also persist over a wide range of infection ranges, but only in hosts that reproduce mostly locally. In general the mean field may well be a good approximation for many systems, even when there are a significant proportion of near neighbour events, but this depends crucially on the ecological context. PMID- 17719609 TI - Polycystic ovary syndrome is associated with genetic polymorphism in the insulin signaling gene IRS-1 but not ENPP1 in a Japanese population. AB - Recent studies indicate that insulin resistance resulting from altered post receptor signaling is associated with polycystic ovary syndrome (PCOS). We hypothesized that insulin receptor substrate-1 (IRS-1) Gly972Arg polymorphism and/or ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) Lys121Gln polymorphism predisposes women to PCOS and that these polymorphisms also affect anthropometric variables, glucose metabolism and androgen synthesis. To test those ideas, we studied the genotypes, indexes of insulin resistance, and hormone profiles in 123 Japanese women with PCOS and 380 healthy Japanese controls. We found that there were significantly more IRS-1 972Arg carriers among the PCOS patients than among the healthy controls (10.6% vs. 4.8%, p=0.029), which is consistent with our finding that women carrying the IRS-1 972Arg allele had a significantly increased risk of developing PCOS (odds ratio: 3.31, 95% confidence interval: 1.49-7.35). By contrast, the ENPP1 Lys121Arg polymorphism was distributed equally among PCOS patients and controls. In addition, neither of these polymorphisms studied affected the anthropometric variables, metabolic parameters or androgen levels of women with PCOS. We conclude that the IRS-1 Gly972Arg polymorphism is associated with PCOS in the Japanese population. PMID- 17719610 TI - Post-mortem stability of blubber DLCs, PCB and tDDT in by-caught harbour porpoises (Phocoena phocoena). PMID- 17719611 TI - Mice lacking NKCC1 have normal olfactory sensitivity. AB - When olfactory receptor neurons respond to odors, a depolarizing Cl(-) efflux is a substantial part of the response. This requires that the resting neuron accumulate Cl(-) against an electrochemical gradient. In isolated olfactory receptor neurons, the Na(+)+K(+)+2Cl(-) cotransporter NKCC1 is essential for Cl( ) accumulation. However, in intact epithelium, a robust electrical olfactory response persists in mice lacking NKCC1. To determine whether NKCC1 is required for normal olfactory sensitivity, olfactory sensitivity was compared between knockout (KO) mice carrying a null mutation for NKCC1 and wild-type (WT) littermates. Using operant behavioral techniques, olfactory sensitivity was measured using a commercial liquid-dilution olfactometer. Detection thresholds for the simple odorants cineole, 1-heptanol, and 1-propanol were compared in KO and WT animals. Regardless of the stimulus conditions employed, no systematic differences in behavioral thresholds were evident between KO and WT animals. We conclude that NKCC1 is not required for normal olfactory sensitivity. PMID- 17719612 TI - Estrogenic constituents of the heartwood of Dalbergia parviflora. AB - From the heartwood of Dalbergia parviflora, five compounds, dalparvin A (1), B (2), C (3), dalparvinol C (4), and neokhriol A (5), along with 11 known compounds, kenusanone G (6), cajanin (7), sophorol (8), alpinetin (9), hesperetin (10), 3'-O-methylorobol, odoratin, (2R)(3R)-2,3-trans 7-hydroxy-5 methoxydihydroflavonol, (6aR, 11aR)-3,8-dihydroxy-9-methoxypterocarpan, (6aR, 11aR)- vesticarpan, and methyl-3,4-dihydroxy-2-methoxybenzoate were isolated and characterized. Isolates were evaluated for their cell proliferation stimulatory activity against MCF-7, T-47D, and BT20 human breast cancer cell lines. Along with 7-10, two compounds 2 and 3 stimulated not only MCF-7, but also T-47D human breast cancer cell proliferation. Compound 6 had activity only against MCF-7 cells, and the activity of 7 was more than equivalent to that of daidzein. On the other hand, none of the isolates had any significant effects on BT20 cell proliferation, and these results indicated that the stimulative activity of these compounds was not general to any cell proliferations. Furthermore, these compounds were tested in the estrogen-responsive transient luciferase reporter assay. PMID- 17719613 TI - Elucidation of active site residues of Arabidopsis thaliana flavonol synthase provides a molecular platform for engineering flavonols. AB - Arabidopsis thaliana flavonol synthase (aFLS) catalyzes the production of quercetin, which is known to possess multiple medicinal properties. aFLS is classified as a 2-oxoglutarate dependent dioxygenase as it requires ferrous iron and 2-oxoglutarate for catalysis. In this study, the putative residues for binding ferrous iron (H221, D223 and H277), 2-oxoglutarate (R287 and S289) and dihydroquercetin (H132, F134, K202, F293 and E295) were identified via computational analyses. To verify the proposed roles of the identified residues, 15 aFLS mutants were constructed and their activities were examined via a spectroscopic assay designed in this study. Mutations at H221, D223, H277 and R287 completely abolished enzymes activities, supporting their importance in binding ferrous iron and 2-oxoglutarate. However, mutations at the proposed substrate binding residues affected the enzyme catalysis differently such that the activities of K202 and F293 mutants drastically decreased to approximately 10% of the wild-type whereas the H132F mutant exhibited approximately 20% higher activity than the wild-type. Kinetic analyses established an improved substrate binding affinity in H132F mutant (Km: 0.027+/-0.0028 mM) compared to wild-type (Km: 0.059+/-0.0063 mM). These observations support the notion that aFLS can be selectively mutated to improve the catalytic activity of the enzyme for quercetin production. PMID- 17719614 TI - C-Glucosidic ellagitannin oligomers from Melaleuca squarrosa Donn ex Sm., Myrtaceae. AB - C-glucosidic ellagitannin dimers were classified as types A-C according to a putative biogenetic oligomerization mode. They were characterized by different positions of the C-C bond between the phenolic acyl unit in one monomer and the benzylic C-1 of the open-chain glucose core in the other monomer. In recent years, four C-glucosidic tannins, melasquanins A-D (18-21), have been found in the leaves of Melaleuca squarrosa Donn ex Sm. (Myrtaceae). These are characterized as a dimer (melasquanin A) of a dimerization mode (type D), and trimers (melasquanins B-D) based on spectroscopic analysis including various two dimensional nuclear magnetic resonance (2D NMR) experiments. Melasquanins B (19) and D (21) are C-glucosidic tannin trimers with a structure containing, non repeating condensation modes, which was hitherto unknown. PMID- 17719615 TI - Evolution and current status of the phytochemistry of nitrogenous compounds. AB - Nitrogen-containing and other secondary plant products have evolved as a consequence of the struggle between the plant and the animal kingdoms, the latter directly or indirectly thriving on plants. During evolution plants developed bioactive and exceedingly complicated chemical structures that serve the purpose of plant defense. It is this property of those plants that has been exploited by mankind as medicines, poisons and recreational drugs. Three classes of nitrogen containing plant products are being reviewed in this article: the alkaloids, the cyanogenic glucosides/glucosinolates and the nonprotein amino acids. It is the interplay of different scientific disciplines such as chemistry, pharmacognosy, medicine, analytics, cell biology, molecular biology, botany and chemotaxonomy that form a new and exciting area called "phytochemistry". It is foreseeable that this integration of disciplines across traditional borders will bring new achievements in phytochemistry, as history has taught us already. PMID- 17719616 TI - Evaluation of a school-based health promotion programme for adolescents aged 12 15 years with focus on well-being related to stress. AB - OBJECTIVE: The aim of this study was to evaluate a school-based adolescent health promotion programme with focus on well-being related to stress. STUDY DESIGN: Interventional and evaluative with tests before and after the intervention. The study was performed in two secondary schools in a town on the west coast of Sweden. METHODS: A health promotion programme comprising massage and mental training was implemented for a single academic year in one school (intervention school, 153 participants) in order to strengthen and maintain well-being. No intervention was implemented in the other school (non-intervention school, 287 participants). A questionnaire was developed and tested, resulting in 23 items distributed across the following six areas: self-reliance; leisure time; being an outsider; general and home satisfaction; school satisfaction; and school environment. RESULTS: A pre- and postintervention comparison of the six areas was made within each school. In the intervention school, the boys maintained a very good or good sense of well-being related to stress in all six areas, while the girls' sense of well-being was maintained in five areas and deteriorated in one area. In the non-intervention school, the boys maintained a very good or good sense of well-being related to stress in four areas and deteriorated in two areas, while the girls' sense of well-being was maintained in two areas and deteriorated in four areas. CONCLUSION: Massage and mental training helped to maintain adolescents' very good or good sense of well-being related to stress. A questionnaire with acceptable validity and reliability was developed and tested in order to evaluate the health promotional approach. However, there is a need for further study to develop both the intervention and the questionnaire for young people. PMID- 17719617 TI - Reservoir interactions and disease emergence. AB - Animal populations act as reservoirs for emerging diseases. In order for transmission to be self-sustaining, a pathogen must have a basic reproduction number R0>1. Following a founding transmission event from an animal reservoir to humans, a pathogen has not yet adapted to its new environment and is likely to have an R0<1. However, subsequent evolution may rescue the pathogen from extinction in its new host. Recent applications of branching process theory investigate how the emergence of a novel pathogen is influenced by the number and rates of intermediate evolutionary steps. In addition, repeated contacts between human and reservoir populations may promote pathogen emergence. This article extends a stepping-stone model of pathogen evolution to include reservoir interactions. We demonstrate that the probability of a founding event culminating in an emerged pathogen can be significantly influenced by ongoing reservoir interactions. While infrequent reservoir interactions do not change the probability of disease emergence, moderately frequent interactions can promote emergence by facilitating adaptation to humans. Frequent reservoir interactions promote emergence even with minimal adaptation to humans. Thus, these results warn against perpetuated interaction between humans and animal reservoirs, as occurs when there are ecological or environmental changes that bring humans into more frequent contact with animal reservoirs. PMID- 17719618 TI - Caloric vestibular stimulation reveals discrete neural mechanisms for coherence rivalry and eye rivalry: a meta-rivalry model. AB - Binocular rivalry is an extraordinary visual phenomenon that has engaged investigators for centuries. Since its first report, there has been vigorous debate over how the brain achieves the perceptual alternations that occur when conflicting images are presented simultaneously, one to each eye. Opposing high level/stimulus-representation models and low-level/eye-based models have been proposed to explain the phenomenon, recently merging into an amalgam view. Here, we provide evidence that during viewing of Diaz-Caneja stimuli, coherence rivalry -- in which aspects of each eye's presented image are perceptually regrouped into rivalling coherent images -- and eye rivalry operate via discrete neural mechanisms. We demonstrate that high-level brain activation by unilateral caloric vestibular stimulation shifts the predominance of perceived coherent images (coherence rivalry) but not half-field images (eye rivalry). This finding suggests that coherence rivalry (like conventional rivalry according to our previous studies) is mediated by interhemispheric switching at a high level, while eye rivalry is mediated by intrahemispheric mechanisms, most likely at a low level. Based on the present data, we further propose that Diaz-Caneja stimuli induce 'meta-rivalry' whereby the discrete high- and low-level competitive processes themselves rival for visual consciousness. PMID- 17719619 TI - Paleoenvironment of Dryopithecus brancoi at Rudabanya, Hungary: evidence from dental meso- and micro-wear analyses of large vegetarian mammals. AB - The environment of the hominoid Dryopithecus brancoi at Rudabanya (Late Miocene of Hungary) is reconstructed here using the dietary traits of fossil ruminants and equids. Two independent approaches, dental micro- and meso-wear analyses, are applied to a sample of 73 specimens representing three ruminants: Miotragocerus sp. (Bovidae), Lucentia aff. pierensis (Cervidae), Micromeryx flourensianus (Moschidae), and one equid, Hippotherium intrans (Equidae). The combination of meso- and micro-wear signatures provides both long- and short-term dietary signals, and through comparisons with extant species, the feeding styles of the fossil species are reconstructed. Both approaches categorize the cervid as an intermediate feeder engaged in both browsing and grazing. The bovid Miotragocerus sp. is depicted as a traditional browser. Although the dental meso-wear pattern of the moschid has affinities with intermediate feeders, its dental micro-wear pattern also indicates significant intake of fruits and seeds. Hippotherium intrans was not a grazer and its dental micro-wear pattern significantly differs from that of living browsers, which may suggest that the fossil equid was engaged both in grazing and browsing. However, the lack of extant equids which are pure browsers prevents any definitive judgment on the feeding habits of Hippotherium. Based on these dietary findings, the Rudabanya paleoenvironment is reconstructed as a dense forest. The presence of two intermediate feeders indicates some clearings within this forest; however the absence of grazers suggests that these clearings were most likely confined. To demonstrate the ecological diversity among the late Miocene hominoids in Europe, the diet and habitat of Dryopithecus brancoi and Ouranopithecus macedoniensis (Greece) are compared. PMID- 17719620 TI - Comparison of green algae Cladophora sp. and Enteromorpha sp. as potential biomonitors of chemical elements in the southern Baltic. AB - The contents of Cd, Cu, Ni, Pb, Zn, Mn, K, Na, Ca and Mg were determined in the green algae Cladophora sp. from coastal and lagoonal waters of the southern Baltic. Factor analysis demonstrated spatial differences between concentration of chemical elements. The algae from the southern Baltic contained more Na and K while the anthropogenic impact of Cu, Pb and Zn was observed in the case of Cladophora sp. and Enteromorpha sp. from the Gulf of Gdansk at the vicinity of Gdynia. This area is exposed to emission of heavy metals from municipal and industrial sources with the main contribution of shipbuilding industry and seaport. The statistical evaluation of data has demonstrated that there exists a correlation between concentrations of Cu, Pb and Zn in both green algae collected at the same time and sampling sites of the Gulf of Gdansk. Our results show that in the case of absence of one species in the investigated area it is still possible to continue successfully the biomonitoring studies with its replacing by second one, i.e. Cladophora sp. by Enteromorpha sp. and vice versa; in consequence reliable results may be obtained. PMID- 17719622 TI - Repeated induction of abortion in bitches and the effect on plasma concentrations of relaxin, progesterone and estradiol-17beta. AB - The aim of the present study was to investigate the effects of two medications on two subsequent abortions and plasma hormone concentrations of dogs. For this purpose, two groups of bitches (n=5 each), received the antiprogesterone aglepristone (Alizine) at 10mg/kg body weight on two subsequent days around day 30 after mating. In group II, the antiprolactin cabergoline (Galastop) was additionally administered po at 5 microg/kg body weight until the start of abortion. The plasma concentrations of relaxin, progesterone (P4) and estradiol 17beta (E2) were measured before, during and after each abortion. During the next cycle after the abortion, the same bitches were mated again and in pregnant animals, induction of abortion was performed as before. During the third cycle, pregnant bitches were allowed to whelp. Termination of first pregnancy occurred significantly earlier after the combined treatment (6.8 versus 10.6 days, p<0.05). In both groups and during both abortions, relaxin varied between individuals; however, there was a continuous decrease after the abortions and no significant differences between groups (p>0.05). In one bitch with high relaxin concentrations before treatment (11.6 ng/ml), a cystic endometrial hyperplasia was diagnosed. In the aglepristone only group, P4 concentrations increased significantly after the first application (p<0.05), then decreased continuously until day 45 after the beginning of abortion. In the combined group, there was a continuous decrease until day 45 (p>0.05). At this time, P4 concentrations between 0.47 and 84.9 nmol/l were measured in both groups. The level of E2 over time was not influenced by any medication. We therefore note that the two medications mainly influenced plasma concentrations of P4 in different ways, probably due to specific treatment-hormone interactions. However, all measurements fell within the range considered normal. PMID- 17719621 TI - Activation of peripheral and spinal histamine H3 receptors inhibits formalin induced inflammation and nociception, respectively. AB - Pharmacological activation of histamine H3 receptors is known to reduce the release of inflammatory peptides, thereby reducing pain and inflammation, but the site(s) and mechanism(s) of these effects are currently unknown. The present study addressed these questions by examining the effects of the H3 agonist immepip and the H3 antagonist thioperamide on nociceptive behaviors and swelling produced during the rat formalin test. Systemic administration of immepip (5 and 30 mg/kg, s.c.) significantly attenuated formalin-induced flinching but not licking responses during both phases. This attenuation was reversed by either systemic (15 mg/kg, i.p.) or intrathecal (20 or 50 microg) administration of thioperamide. Furthermore, immepip (30 mg/kg, s.c.) significantly inhibited formalin-induced swelling, an action which was completely reversed by systemic (15 mg/kg, i.p.), but not intrathecal (50 microg) thioperamide. Also consistent with this pattern, intrathecal immepip (50 microg) reduced flinching responses, but had no effect on formalin-induced paw swelling. The present findings suggest that activation of H3 receptors located on peripheral and spinal terminals of deep dermal fibers attenuates formalin-induced swelling and flinching, respectively. Pharmacological stimulation of H3 receptors could be an important therapeutic approach for many disorders related to deep dermal or inflammatory pain. PMID- 17719623 TI - Effect of a porcine circovirus type 2 infection on embryos during early pregnancy. AB - The aim of the present study was to assess the effects of porcine circovirus type 2 (PCV2) on porcine embryos and their receptor sows during the first 21 days of pregnancy. Hatched blastocysts exposed to 10(5.0) TCID50 PCV2 per ml (strain 1121, fifth passage PK15) and negative control embryos were transferred to PCV2 immune receptor sows at the 7th day of the cycle. Two weeks after transfer (D21), the receptor sows were euthanized and embryos were recovered. They were assessed macroscopically for viability and examined for viral antigen-positive cells by immunoperoxidase staining. The embryonic survival rate of the PCV2-exposed embryos (6.4%, 7 viable embryos out of 110 transferred) was significantly lower than the survival rate of the negative control embryos (65.4%, 34 viable embryos out of 52 transferred). All of the non-viable PCV2-exposed embryos (n=9) displayed immunohistochemical positive signals for PCV2-antigen in degenerated tissues. In the PCV2-exposed embryos that were categorized as viable at D21, small clusters (n=4) or no PCV2-positive cells (n=3) were detected. The pregnancy results of the receptor sows that received PCV2-exposed embryos (1/5) were considerably different from the negative control receptors (2/2), with 3 out of 5 sows displaying a regular return to oestrus. In conclusion, it can be stated that PCV2 can replicate in embryos and might lead to embryonic death. In a small proportion of embryos, PCV2 exposure does not have a detrimental effect on embryo development before D21. PMID- 17719624 TI - The acute effect of bull presence on plasma profiles of luteinizing hormone in postpartum, anoestrous dairy cows. AB - The objective of this study was to investigate whether bull exposure affects LH profiles in postpartum, anoestrous dairy cows. Eight cows between 10 and 17 days after parturition were used. On Day 1, blood samples were taken at 10 min intervals for 8 h. On Day 2, blood sampling continued at 10 min intervals and after 2 h a bull was introduced behind a fence, and blood sampling continued for another 8 h. Time of resumption of luteal activity was between 25 and more than 80 days after parturition for these animals and was not related (P>0.1) with frequency of LH pulses, amplitude of pulses and basal LH concentration on either Day 1 or Day 2. In 6 of the 8 cows, average and basal LH concentration were greater (P<0.001) during the 8 h of bull presence (0.56 +/- 0.33 and 0.39 +/- 0.26 ng/ml, respectively) compared to the 8 h without a bull (0.50 +/- 0.30 and 0.35 +/- 0.24 ng/ml, respectively). Pulse amplitude did not differ (P=0.85) between Day 2 (0.45 +/- 0.24 ng/ml) or Day 1 (0.45 +/- 0.14 ng/ml). LH pulse frequency was greater (P<0.1) on Day 2 (5.3 pulses/8h) compared to the Day 1 (4.6 pulses/8h). In conclusion, fenceline bull exposure early postpartum seems to have an acute effect on LH-release in anoestrous dairy cows. Whether sustained bull exposure can hasten first ovulation after calving through an effect on LH release in dairy cows is an interesting area of research. PMID- 17719625 TI - Effect of coculture with oviduct epithelial cells on viability after transfer of vitrified in vitro produced goat embryos. AB - This study evaluates the effect of coculture with goat oviduct epithelial cells (GOEC) on the pregnancy rate, embryo survival rate and offspring development after direct transfer of vitrified/thawed caprine in vitro produced (IVP) embryos. Oocytes were recovered from slaughterhouse goat ovaries, matured and inseminated with frozen/thawed capacitated semen, and presumptive zygotes were randomly cultured in synthetic oviduct fluid (SOF) (n=352) or GOEC (n=314). The percentage of cleaved embryos reaching the blastocyst stage was 28% and 20% in SOF and GOEC, respectively (P<0.05). Overall, 26 blastocysts of SOF were transferred freshly in pairs to recipient goats, whereas 58 of SOF and 36 of GOEC were vitrified and transferred directly in pairs to recipient goats after thawing without removal of cryoprotectants or morphological evaluation. The kidding rate was 92% for SOF fresh, 14% for SOF vitrified (P<0.001) and 56% for GOEC vitrified (P<0.05); the difference was also significant between vitrified groups (P<0.01). The embryo survival rate was 62% for SOF fresh, 9% for SOF vitrified (P<0.001) and 33% for GOEC vitrified (P<0.05) with a significant difference between vitrified groups (P<0.01). The results showed that the coculture of IVP goat embryos with GOEC significantly improves the pregnancy and embryo survival rates and leads to the birth of healthy offspring. However, further research using more defined GOEC coculture is required to confirm its capacity to increase the success rate of IVP embryo technology in goat. PMID- 17719626 TI - Polymerization stress of resin composites as a function of system compliance. AB - OBJECTIVES: Evaluate the effect of testing system compliance on polymerization stress and stress distribution of composites. METHODS: Composites tested were Filtek Z250 (FZ), Herculite (HL), Tetric Ceram (TC), Helio Fill-AP (HF) and Heliomolar (HM). Stress was determined in 1-mm thick specimens, inserted between two rods of either poly(methyl methacrylate), PMMA, or glass. Experimental nominal stress (sigmaexp) was calculated by dividing the maximum force recorded 5 min after photoactivation by the cross-sectional area of the rod. Composites' elastic modulus (E) was obtained by three-point bending. Data were submitted to one-way ANOVA/Tukey's test (alpha=0.05). Stress distribution on longitudinal (sigmay) and transverse (sigmax) axes of models representing the composites with the highest and lowest E (FZ and HM, respectively) were evaluated by finite element analysis (FEA). RESULTS: sigmaexp ranged from 5.5 to 8.8 MPa in glass and from 2.6 to 3.4 MPa in PMMA. Composite ranking was not identical in both substrates, since FZ showed sigmaexp statistically higher than HM in glass, while in PMMA FZ showed values similar to the other composites. A strong correlation was found between stress reduction (%) from glass to PMMA and composite's E (r2=0.946). FEA revealed that system compliance was influenced by the composite (FZ led to higher compliance than HM). sigmax distribution was similar in both substrates, while sigmay distribution showed larger areas of compressive stresses in specimens built on PMMA. SIGNIFICANCE: sigmaexp determined in PMMA was 53-68% lower than in glass. Composite ranking varied slightly due to differences in substrates' longitudinal and transverse deformation. PMID- 17719627 TI - Influence of Tg, viscosity and chemical structure of monomers on shrinkage stress in light-cured dimethacrylate-based dental resins. AB - OBJECTIVES: The aim of this study was to investigate the influence of the molecular mobility and the chemical structure of dimethacrylates most commonly used in dental composites on shrinkage stress from experimental matrices. METHODS: Three established neat monomers BisGMA (B), UEDMA (U) and TEGDMA (T), two experimental comonomers BisGMA-based (B-T(70/30) and B-T(50/50)) and two comonomers UEDMA-based (U-T(88/11) and U-T(66/33)) in weight%, were elaborated. Camphorquinone (CQ) and N,N-cyanoethylmethylaniline (CEMA), as photoinitiator and reducing agent, were added. Then the matrices were mixed by centrifugal force at room temperature. The viscosity (eta), the glass transition temperature of the monomers and comonomers systems (T(g(monomer)) and the maximum shrinkage stress (MSS) of each material (five replications) were statistically analysed by one-way ANOVA/Tuckey's test and Pearson's correlation procedure (p = 0.05). RESULTS: All formulations exhibited a newtonian rheological behavior. The viscosity of the comonomers systems can be divided in two groups: the pair B-T(70/30)/U-T(88/11) with the viscosity 3.5+/-3.10(-3)Pa.s and the pair B-T(50/50)/U-T(66/33) with the viscosity 0.28+/-3.10(-3)Pa.s. This pairs constituted samples allowing to compare the shrinkage stress of the BisGMA and UEDMA-based matrices with each other. The T(g(monomer)) of each group showed equivalent statistically values: -37.1 +/- 0.02 degrees C (U-T(88/11)) with -39.3 +/- 0.02 degrees C (B-T(70/30)) for the 3.5 Pa.s pair, and -53.1 +/- 0.03 degrees C (U-T(66/33)) with -58.5 +/- 0.01 degrees C (B-T(50/50)) for the 0.28 Pa.s one. There was a correlation between eta and T(g(monomer)) (r < 0.45 and p < 0.01). In decreasing order, the shrinkage stress was 14.11 +/- 0.3 MPa (T), 10.64 +/- 0.6 MPa (U-T(66/33)), 8.16 +/- 0.25 MPa (B-T(50/50)) without a significant difference compared to 8.04 +/- 0.5 MPa (U T(88/11)), 6.83 +/- 0.52 MPa (U), 4.44 +/- 0.25 MPa (B-T(70/30)) and 0.33 +/- 0.3 MPa (B). There was a negative correlation between eta (r < -0.42 and p < 0.01), T(g(monomer)) (r < -0.41 and p < 0.01) and MSS. Whatever the viscosity, the UEDMA based matrices developed higher shrinkage stresses than the BisGMA homologues. SIGNIFICANCE: The shrinkage stress development increase with the molecular mobility of the reacting medium. For the same molecular mobility, the large differences in stress values of the matrices studied are correlated to the structure and particularly the functionality of the monomers used. PMID- 17719628 TI - Structural and thermodynamic properties of rice starches with different genetic background Part 2. Defectiveness of different supramolecular structures in starch granules. AB - High-sensitivity differential scanning microcalorimetry (HSDSC), small-angle X ray scattering (SAXS), light (LM) and scanning electronic (SEM) microscopy techniques were used to study the defectiveness of different supramolecular structures in starches extracted from 11 Thai cultivars of rice differing in level of amylose and amylopectin defects in starch crystalline lamellae. Despite differences in chain-length distribution of amylopectin macromolecules and amylose level in starches, the invariance in the sizes of crystalline lamellae, amylopectin clusters and granules was established. The combined analysis of DSC, SAXS, LM and SEM data for native starches, as well as the comparison of the thermodynamic data for native and annealed starches, allowed to determine the structure of defects and the localization of amylose chains in crystalline and amorphous lamellae, defectiveness of lamellae, clusters and granules. It was shown that amylose "tie chains", amylose-lipid complexes located in crystalline lamellae, defective ends of double helical chains dangling from crystallites inside amorphous lamellae ("dangling" chains), as well as amylopectin chains with DP 6-12 and 25-36 could be considered as defects. Their accumulation can lead to a formation of remnant granules. The changes observed in the structure of amylopectin chains and amylose content in starches are reflected in the interconnected alterations of structural organization on the lamellar, cluster and granule levels. PMID- 17719629 TI - Connexin 43 expression of foreign body giant cells after implantation of nanoparticulate hydroxyapatite. AB - In bone a role of connexin 43 has been implicated with the fusion of mononuclear precursors of the monocyte/macrophage lineage into multinucleated cells. In order to investigate the putative role of connexin 43 in formation of bone osteoclast like foreign body giant cells which are formed in response to implantation of biomaterials, nanoparticulate hydroxyapatite had been implanted into defects of minipig femura. After 20 days the defect areas were harvested and connexin 43 expression and synthesis were investigated by using immunohistochemistry, Western Blot, and in situ hybridization within macrophages and osteoclast-like foreign body giant cells. Morphological analysis of gap junctions is performed ultrastructurally. As shown on protein and mRNA level numerous connexin 43 positive macrophages and foreign body giant cells (FBGC) were localized within the granulation tissue and along the surfaces of the implanted hydroxyapatite (HA). Besides, the formation of FBGC by fusion of macrophages could be shown ultrastructurally. Connexin 43 labeling observed on the protein and mRNA level could be attributed to gap junctions identified ultrastructurally between macrophages, between FBGC, and between FBGC and macrophages. Annular gap junctions in the cytoplasm of FBGC pointed to degradation of the channels, and the ubiquination that had occurred in the course of degradation was confirmed by Western blot analysis. All in all, the presently observed pattern of connexin 43 labeling refers to an functional role of gap junctional communication in the formation of osteoclast-like foreign body giant cells formed in response to implantation of the nanoparticulate HA. PMID- 17719630 TI - [CT angiography for the diagnosis of brain death: recommendations of the French Society of Neuroradiology (SFNR)]. PMID- 17719631 TI - MRI of the 'Alzheimer syndrome'. AB - Interest in the identification of cognitive decline in its earliest manifestations and the heterogeneity of clinically diagnosed Alzheimer's disease (AD) explain the growing number of neuroimaging studies of AD. Alzheimer-type lesions are associated with loss of neurons, and magnetic resonance imaging (MRI) can detect predominantly left atrophic changes in the entorhinal cortex, amygdala and anterior hippocampus several years before the onset of clinical symptoms. Cerebrovascular disease can mimic AD in the elderly whereas MR markers of subcortical vascular disease-leukoaraiosis, lacunar infarcts, microbleeds, ventricular enlargement, cortical and hippocampal atrophy-appear to be structural changes associated with vascular-related cognitive impairment. Furthermore, analysis of prodromal forms of late-onset dementia of Alzheimer's type (DAT) differentiates amnesic single-domain mild cognitive impairment, which shows MR patterns similar to those observed in early-onset DAT, from other predementia patterns without atrophy at the earliest sites of AD pathology. Mesiotemporal atrophy on MRI predicts late-onset DAT, but the current rating scales or measurements of mesiotemporal atrophy do not differentiate anteromesial temporal atrophy that is highly suggestive of AD from predominantly hippocampal atrophy, suggestive of non-AD damage and, usually, vascular disease. The other, most common MRI predictors of late-onset DAT may be considered indirect markers of arterial senescence whereas brain atrophy is diffusely milder and MR markers of small-vessel disease more frequent in late-onset, compared with early-onset, DAT. Thus, MRI suggests an overestimation of AD pathology while underestimating 'arteriosclerotic brain degeneration' in the clinical picture of 'Alzheimer syndrome'. PMID- 17719632 TI - Apparent diffusion coefficient of pituitary macroadenoma evaluated with line-scan diffusion-weighted imaging. AB - OBJECTIVE: The goal of this study was to evaluate the consistency of pituitary macroadenoma using apparent diffusion coefficient (ADC) with line-scan diffusion weighted imaging (LSDWI). METHODS: Patients with pituitary macroadenoma (n=19) were studied prospectively. The LSDWI was performed using a maximum b factor of 1000 s/mm2. The consistency of macroadenoma was rated as soft, intermediate or hard at transsphenoidal surgery. The ADC values of tumors were compared with the tumor-consistency ratings. RESULTS: A soft consistency was found at surgery in 13 patients (mean ADC: 0.84+/-0.1x10(-3) mm2/s); an intermediate consistency was observed in six patients (mean ADC: 0.81+/-0.16x10(-3) mm2/s). No tumors of hard consistency were found. There was no significant difference in ADC values between tumors of soft consistency compared with tumors of intermediate consistency (P=0.37). CONCLUSIONS: A relationship between tumor consistency and the ADCs of soft and intermediate macroadenomas was not shown in this study using LSDWI. PMID- 17719633 TI - The use of the shanny Lipophrys pholis for pollution monitoring: a new sentinel species for the northwestern European marine ecosystems. AB - The contamination of aquatic ecosystems by organic contaminants such as polycyclic aromatic hydrocarbons (PAHs) is a matter of great concern. Mussels have been extensively used as sentinel species in a large number of monitoring programs. However, the use of bivalves as the sole species has some limitations, because they are not as responsive as fish to Aryl Hydrocarbon Receptor agonists. Hence, for many marine areas, there is the need to validate new sentinel fish species that can be used in the assessment of pollution by organic contaminants. The shanny Lipophrys pholis is an intertidal fish that combines many characteristics required in a sentinel species: is abundant and easy to catch, has a wide geographical distribution and restrict home range. After larvae recruitment to the intertidal rocky shores, they remain in the same area for the rest of the life-cycle, thus reflecting local pollutants exposure. In order to evaluate the species sensitivity to organic contaminants under field conditions, L. pholis were collected at six sites reflecting different degrees of anthropogenic contamination. The induction of two biomarkers extensively validated in the assessment of PAHs contamination ethoxyresorufin-O-deethylase activity (EROD) and Fluorescent Aromatic Compounds (FACs) was evaluated. In parallel, mussels were collected at the same locations and levels of 16 PAHs and selected heavy metals determined. Overall, the specimens collected in the urban areas showed a significant induction of EROD and FACs (up to a six-fold induction) if compared with the reference sites. Additionally, a positive correlation was observed between the biomarkers and PAHs levels in mussel tissues. Even though further validation is currently in progress, the available data indicate that L. pholis is responsive to organic contaminants such as PAHs, suggesting its future integration in monitoring programmes designed to evaluate the presence of these contaminants in European marine ecosystems. PMID- 17719634 TI - Glomerular expression of large polyomavirus T antigen in binary tet-off regulated transgenic mice induces apoptosis, release of chromatin and initiates a lupus like nephritis. AB - Binary tetracycline-regulated polyomavirus large T antigen transgenic mice were generated to study immunological tolerance for nucleosomes. Expression of T antigen resulted in binding of the protein to chromatin, and released T antigen nucleosome complexes from dying cells maintained anti-dsDNA and anti-nucleosome antibody-production by activating autoimmune nucleosome-specific B cells and CD4+ and CD8+ T antigen specific T cells. Glomerular T antigen expression was observed in these mice. Here, we demonstrate that this expression was linked to glomerular cell apoptosis, release of nucleosomes and association of nucleosomes with glomerulus basement membranes, detected as electron dense structures. Immune electron microscopy (IEM) revealed that these structures were glomerular targets for induced anti-dsDNA and anti-T antigen antibodies. Co-localization IEM demonstrated that in vivo-bound auto-antibodies co-localized with experimental monoclonal antibodies to dsDNA and to T antigen. A comparative analysis of glomeruli from nephritic (NZWxNZB)F1 and T antigen expressing transgenic mice revealed deposition of nucleosomes in glomerular capillary and mesangial matrix membranes and binding of anti-nucleosome antibodies in both mice strains. A controlled experimental model that may elucidate the initial events accounting for nucleosome-mediated nephritis has not been available. The transgenic mouse may be important to describe early immunological and cellular events accounting for the enigmatic lupus nephritis. PMID- 17719635 TI - UbcH8 regulates ubiquitin and ISG15 conjugation to RIG-I. AB - The RNA helicase retinoic inducible gene I (RIG-I) recognizes viral double stranded RNA and initiates signaling cascades that lead to activation of the protein kinases IKKalphabeta, TBK1 and IKKepsilon, and to subsequent activation of the transcription factors NF-kappaB and IRF3. We recently reported that RIG-I was ubiquitinated by RNF125, an ubiquitin E3 ligase, leading to proteasomal degradation. RIG-I is also reported to be ISGylated by an unidentified ISG15 (IFN stimulated gene, 15kDa) E3 ligase. UbcH8, an ubiquitin E2 conjugating enzyme, was shown to be involved in RIG-I ISGylation. Here, we found that UbcH8 suppressed RIG-I ubiquitination by RNF125, and this suppression was relieved by ectopic expression of ISG15. Alternately, ISG15 conjugation to RIG-I was suppressed by RNF125. By analyzing this regulatory circuit, we found that UbcH8 and ISG15 are functional regulators of RNF125 E3 ligase activity, which regulates the level of ubiquitin and ISG15 conjugation of RIG-I. PMID- 17719636 TI - Structural effect of deglycosylation and methionine oxidation on a recombinant monoclonal antibody. AB - Methionine (Met) is one of the most susceptible amino acids to oxidation. Met256 (CH2-Met15.1) and Met432 (CH3-Met107) of a recombinant humanized monoclonal IgG1 antibody are located in the CH2 and CH3 domains, respectively. In three dimensional structure, these two Met residues are close to the CH2-CH3 interface. In close proximity, oligosaccharides on the conserved asparagine (Asn) residues are enclosed in the CH2 domains. The relationship of Met oxidation with oligosaccharides and their effect on the structure of the antibody was investigated. Removal of oligosaccharides did not alter the oxidation rates of Met256 and Met432, however it caused significant structural changes as evidenced by the susceptibility of the deglycosylated antibody to trypsin and chymotrypsin. Oxidation of Met256 and Met432 did not cause significant conformational changes of the antibody with oligosaccharides, however oxidation of these Met residues accelerated degradation of the deglycosylated antibody. Analysis by mass spectrometry indicated that most of the protease cleavage sites were in the CH2 domains, which suggested that conformational changes induced by the removal of oligosaccharides and further by Met oxidation were local to the CH2 domains. PMID- 17719638 TI - The context of HLA-DR/CD18 complex in the plasma membrane governs HLA-DR-derived signals in activated monocytes. AB - HLA-DR-derived signals in activated monocytes mediate both pro-inflammatory cytokine production and caspase-independent death, and have been postulated to play a role in inflammation and in its resolution, respectively. Herein, using the monocytic/macrophagic human cell line THP-1 primed with IFNgamma (IFNgamma primed THP-1), we investigated how HLA-DR may integrate both signals. Our inhibition studies demonstrated that if cell death is dependent on PKCbeta activation, the induction of TNFalpha gene expression relies on PTK activation, in particular the Src family of kinases, but both cell responses implicate the beta2-integrin CD18. Accordingly, sequential immunoprecipitation experiments demonstrated that following engagement of HLA-DR on IFNgamma-primed THP-1 cells, the HLA-DR/CD18 complex physically associates with PKCbeta and with PTK. Pharmacological disruption of lipid rafts microdomains abolished the assembly of HLA-DR/CD18/PTK signaling complex, HLA-DR-mediated tyrosine activation, and the PTK-dependent TNFalpha expression in IFNgamma-primed THP-1 cells. In contrast, HLA-DR/CD18/PKCbeta complex was still formed and able to mediate cell death after cholesterol depletion of these cells. These results indicate that while the integrity of lipid rafts is necessary for the transduction of cytokine gene expression through the HLA-DR/CD18 complex, it is not necessary for the induction of the HLA-DR/CD18-dependent cell death. Thus, our study provides experimental evidence indicating the compartmentalization of HLA-DR/CD18 complex within or outside lipid rafts as a mechanism through which HLA-DR can integrate both PTK and PKCbeta signals leading to activation and death, respectively, of activated monocytes. This might provide new insights into how MHC class II signaling may regulate inflammatory response. PMID- 17719639 TI - Tracking phenotypically and functionally distinct T cell subsets via T cell repertoire diversity. AB - Antigen-specific T cell receptors (TCRs) recognise complexes of immunogenic peptides (p) and major histocompatibility complex (MHC) glycoproteins. Responding T cell populations show profiles of preferred usage (or bias) toward one or few TCRbeta chains. Such skewing is also observed, though less commonly, in TCRalpha chain usage. The extent and character of clonal diversity within individual, antigen-specific T cell sets can be established by sequence analysis of the TCRVbeta and/or TCRValpha CDR3 loops. The present review provides examples of such TCR repertoires in prominent responses to acute and persistent viruses. The determining role of structural constraints and antigen dose is discussed, as is the way that functionally and phenotypically distinct populations can be defined at the clonal level. In addition, clonal dissection of "high" versus "low" avidity, or "central" versus "effector" memory sets provides insights into how these antigen specific T cell responses are generated and maintained. As TCR diversity potentially influences both the protective capacity of CD8+ T cells and the subversion of immune control that leads to viral escape, analysing the spectrum of TCR selection and maintenance has implications for improving the functional efficacy of T cell responsiveness and effector function. PMID- 17719640 TI - Follow-up of nonarteritic anterior ischemic optic neuropathy with optical coherence tomography. AB - PURPOSE: To study the characteristics of nonarteritic anterior ischemic optic neuropathy (NAION) as measured with optical coherence tomography (OCT) at diagnosis and during the first year after the episode. DESIGN: Cohort study. PARTICIPANTS: Twenty-seven patients diagnosed with NAION in our center between April 1, 2004 and March 31, 2006. METHODS: Patients diagnosed with NAION underwent at the time of diagnosis and 6 weeks and 3, 6, and 12 months after presentation a complete ophthalmologic evaluation, including determination of Snellen visual acuity (VA), visual fields (VFs) (standard automated perimetry, Swedish Interactive Threshold Algorithm strategy 24-2), and optic nerve head (ONH) scanning with StratusOCT. MAIN OUTCOME MEASURES: Characteristics of the ONH and their relationship with VA and VFs. RESULTS: Initial mean retinal nerve fiber layer (RNFL) thickness in the affected eye was 200.9 microm (standard deviation [SD], 52.3 microm); this represented a 96.4% increase relative to the fellow eye. Percentages of RNFL loss 3, 6, and 12 months after onset were 38.9%, 42.3%, and 43.9%, respectively. At the 6-month visit, RNFL percentage decreases for the superior, nasal, inferior, and temporal quadrants were 51.5%, 28.5%, 41.2%, and 38.2%, respectively. Reduction in the superior quadrant RNFL thickness was statistically higher. Using regression analysis, it was found that for every micrometer of mean RNFL thickness lost there was a 2-decibel decrease in VF mean deviation (MD) and that there was a 1-line drop in Snellen VA for every 1.6 microm lost. The mean ONH area was 2.6 mm2 (SD, 0.4) in the unaffected eye; there was no correlation with VA, VF MD, or RNFL thickness of the affected eye at the last follow-up visit. CONCLUSIONS: Optical coherence tomography can diagnose optic disc edema and monitor RNFL loss over time. It is most useful at onset and 6 months after NAION, when RNFL loss has reached a plateau and is correlated with visual function. Future studies that aim to determine if a drug or intervention is useful for treating NAION may include OCT assessment of the RNFL thickness, because it provides an objective outcome measure correlated with visual performance. PMID- 17719641 TI - Factors affecting the outcome of trabeculectomy: an analysis based on combined data from two phase III studies of an antibody to transforming growth factor beta2, CAT-152. AB - PURPOSE: To determine the factors affecting trabeculectomy success. DESIGN: Retrospective analysis of 2 randomized controlled trials comparing an antibody against transforming growth factor beta2 (TGF-beta2) with vehicle (placebo) for prevention of fibrosis after trabeculectomy, in which there was no significant difference between the treatment groups. PARTICIPANTS: Data were from patients (n = 726) with a diagnosis of primary open-angle glaucoma, chronic angle-closure glaucoma, pseudoexfoliative glaucoma, or pigmentary glaucoma (PG) who had an intraocular pressure (IOP) > 21 mmHg and visual field or optic disc changes characteristic of glaucoma and were taking the maximum tolerated dose of medication before trabeculectomy. METHODS: Patients had trabeculectomy and 4 subconjunctival injections of a human monoclonal antibody to TGF-beta2 (CAT-152) or a placebo. The definition of trabeculectomy success in the protocols was an IOP between 6 and 16 mmHg inclusive at months 6 and 12. Analyses of success used factors identified by ophthalmic experts. MAIN OUTCOMES MEASURES: Covariates analyzed included patient age, black race, gender, time since diagnosis, primary diagnosis, country, diabetes, mean defect, cup-to-disc (C/D) ratio, suture type, anesthetic, flap type, IOP at listing for surgery, suture release/lysis, needling, reformed anterior chamber, wound leak, severe bleb vascularity, and bleb microcysts. RESULTS: A stepwise logistic regression model found the following predictors of treatment success: PG (odds ratio [OR], 4.11; 95% confidence interval [CI], 1.41-11.99), high C/D ratio (OR, 2.84; 95% CI, 1.15 6.99), and use of a corneal traction suture (OR, 1.67; 95% CI, 1.09-2.56). A negative relationship was found for black race (OR, 0.28; 95% CI, 0.13-0.62); treatment in France (OR, 0.35; 95% CI, 0.17-0.70), Sweden (OR, 0.17; 95% CI, 0.05 0.58), Spain (OR, 0.37; 95% CI, 0.21-0.68), Poland (OR, 0.53; 95% CI, 0.32-0.88), or Hungary (OR, 0.14; 95% CI, 0.06-0.34); and suture release/lysis (OR, 0.34; 95% CI, 0.22-0.53). The effect of needling was marginally statistically significant (OR, 0.56; 95% CI, 0.31-1.01). CONCLUSIONS: Successful trabeculectomy outcome was associated with PG, higher C/D ratio, and corneal traction suturing. Factors associated with surgical failure were black race and suture release/lysis. Intercountry differences also were observed. PMID- 17719642 TI - Comparison of parameters from Heidelberg Retina Tomographs 2 and 3. AB - PURPOSE: To compare stereometric parameters and classification results from the Heidelberg Retina Tomograph version 2 (HRT2); HRT3; and HRT3 Glaucoma Probability Score (GPS), an automated method of obtaining optic nerve head analysis without the need for manual definition of disc margin. DESIGN: Retrospective cross sectional study. PARTICIPANTS: Five hundred four eyes from 281 consecutive subjects (glaucoma, glaucoma suspect, and healthy) evaluated in a glaucoma clinic. METHODS: All participants had HRT2 scanning of the optic nerve head. Inclusion criteria were scans with good centration and focus, even illumination, an overall quality score by HRT3 of acceptable or better, and standard deviation < 50 mum. A Bland-Altman analysis was used for the comparison of HRT2 and HRT3. From these results, calibration equations were determined to permit conversion of the measurements between devices. The agreement between HRT2 and HRT3 Moorfields regression analysis (MRA) and HRT3 GPS classification methods was measured using kappa statistics. MAIN OUTCOME MEASURES: Heidelberg Retina Tomograph version 2 and HRT3 stereometric parameters, MRA, and global GPS. RESULTS: There was a statistically significant difference between HRT2 and HRT3 global disc area, rim area, cup area, rim volume, cup volume, height variation contour, and retinal nerve fiber layer cross-sectional area stereometric parameters. All of those parameters were smaller using HRT3, due to a manufacturer-reported horizontal scaling error of 4% in HRT2 that was corrected in HRT3. kappas for agreement were 0.60 between classifications (within normal limits, borderline, and outside normal limits) of MRA by HRT2 and HRT3 and 0.47 between HRT3 MRA and GPS. CONCLUSIONS: The HRT3 generally provided smaller stereometric disc measurements than HRT2. There was no clear conversion between HRT3 and GPS parameters, as the 2 methods for measuring the stereometric parameters differ. PMID- 17719643 TI - Cytogenetics of uveal melanoma: a 7-year clinical experience. AB - PURPOSE: Chromosome 3 loss and chromosome 8 gains in uveal melanoma are associated with metastatic death. Since 1999, we have offered cytogenetic analysis to patients treated by local resection or enucleation. This study correlated our cytogenetic results with clinical and histologic predictors and disease-specific mortality. DESIGN: Nonrandomized case series. PARTICIPANTS: Three hundred fifty-six patients with uveal melanoma with data on chromosome 3 and chromosome 8. METHODS: Tumor diameter was measured by echography. Cell type, presence of closed connective tissue loops, and mitotic rate were determined histopathologically. Fluorescence in-situ hybridization was performed using centromeric probes for chromosomes 3 and 8 and for c-myc. Patients were flagged at the National Health Service Cancer Registry, which notified us of any deaths. Statistics included Cox multivariate analysis and Kaplan-Meier analysis. MAIN OUTCOME MEASURES: Disease-specific mortality, according to clinical, histologic and cytogenetic features as well as correlation between cytogenetic variables and other mortality predictors, including a predictive index. RESULTS: The patients had a mean age of 61.9 years. The tumors showed no cytogenetic abnormalities of chromosomes 3 or 8 in 42%, chromosome 8 gains in 11%, monosomy 3 in 21%, and both abnormalities in 27%. These correlated with ciliary body involvement (P<0.001), extraocular spread (P = 0.007), large basal tumor diameter (P<0.001), epithelioid cellularity (P<0.001), closed connective tissue loops (P<0.001), and mitotic rate exceeding 4/40 high power fields (P<0.001). By the study close, 76 patients had died (67 from metastasis). Cox multivariate analysis showed the most significant factors to be basal tumor diameter (P<0.001), monosomy 3 (P<0.001), and epithelioid cellularity (P = 0.004). A predictive index (PI) was derived from these variables. Kaplan-Meier analysis showed that 5-year metastatic death rates ranged from 0% in 84 patients with low-grade melanoma (PI<19) to 66% in 100 patients with high-grade tumor (PI>26; 95% confidence interval, 53%-80%). CONCLUSION: Cytogenetic analysis of chromosomes 3 and 8 enhances prediction of disease-specific mortality after treatment of uveal melanoma but must be interpreted together with tumor diameter and cell type. PMID- 17719644 TI - Report and analysis of a scarlet fever outbreak among adults through food-borne transmission in China. AB - BACKGROUND: Scarlet fever is caused by group A beta-hemolytic streptococci (GAS). The clinical syndrome has receded in recent years, but occasionally explosive outbreaks do occur likely due to the emergence of GAS with virulence factors peculiar to this syndrome. METHODS: Following the notification of an unexpectedly large number of scarlet fever cases amongst adults associated with a school in Ningbo, China, in June 2006, the epidemiological and clinical features of the outbreak were investigated. Logistic regression was conducted to investigate the risk factors of the outbreak and its transmission route. RESULTS: Forty five individuals suffered scarlet fever with an attack rate of 4.98% (45/904). There was a single peak in the epidemic curve, with the majority of the cases occurring during the first two days of the outbreak. The median age of cases was 35.5 years (range 17-65). Most patients had fever (43/45), sore throat (40/45), scarlatinoid rash (39/45) and strawberry-like tongue (30/45). In laboratory detection, 45 cases' throat swabs samples were collected and GAS were isolated from 8 throat swabs samples. All of the cases, except for 2, had eaten the Plain Boiled Chicken (PBC) for lunch on June 6th, and teaching staff and students who had not eaten the PBC were not affected by the epidemic. Logistic regression analysis indicated that PBC was a key risk factor (OR=21.0, P<0.05). The chef of the school refectory was responsible for washing, braising, cutting, and distributing the PBC, and was identified as the likely source. CONCLUSIONS: We describe an outbreak of scarlet fever caused by GAS-contaminated food. PMID- 17719645 TI - Backflow and Vacutainers. PMID- 17719646 TI - Variations in 10-month-old infant imitation of people and things. AB - To explore 10-month-old infants' abilities to engage in intentional imitation, they were shown a human agent, a non-human agent (stuffed animal), and a surrogate object (mechanical pincers) model actions on objects. The tendency of infants to perform the target act was compared in several situations: (a) after test items were manipulated but the target action was not shown, (b) after the target act was demonstrated successfully, and (c) after the target act was demonstrated unsuccessfully. Although infants imitated the successful actions of human and non-human agents, they completed the unsuccessful actions of humans only. Toward the surrogate object infants did not respond differentially. These findings suggest that although infant may mimic the actions of human and non human agents, they only engage in intentional imitation with people. PMID- 17719647 TI - An update on somatostatin receptor signaling in native systems and new insights on their pathophysiology. AB - The peptide somatostatin (SRIF) has important physiological effects, mostly inhibitory, which have formed the basis for the clinical use of SRIF compounds. SRIF binding to its 5 guanine nucleotide-binding proteins-coupled receptors leads to the modulation of multiple transduction pathways. However, our current understanding of signaling exerted by receptors endogenously expressed in different cells/tissues reflects a rather complicated picture. On the other hand, the complexity of SRIF receptor signaling in pathologies, including pituitary and nervous system diseases, may be studied not only as alternative intervention points for the modulation of SRIF function but also to exploit new chemical space for drug-like molecules. PMID- 17719648 TI - Endocannabinoid signaling in the spinal locomotor circuitry. AB - To understand how the spinal central pattern generators produce locomotor movements, it is necessary to characterize the network's connectivity, the intrinsic properties of the constituent neurons and the modulatory mechanisms. Modulation operating within spinal locomotor networks is required for the generation of the final motor output. In this review, we have summarized how endocannabinoids released by locomotor network neurons contribute to setting the baseline locomotor frequency. They are synthesized on demand as a result of activation of mGluR1 and act as retrograde messengers to depress inhibitory synaptic transmission. We also discuss how endogenous activation of mGluR1 contributes to the normal operation of the spinal locomotor network and the underlying cellular and synaptic mechanisms. PMID- 17719649 TI - Microfluorimetry defines early axonal damage in a rat model of optic neuritis: a novel method targeting early CNS autoimmunity. AB - Autoimmune optic neuritis is a common early manifestation of multiple sclerosis (MS), yet early therapeutic interventions for MS often have high ocular toxicity associated with increased risks for glaucoma, cataract, or retinopathy. This need to discover better early treatment options prompted our development of a sensitive and reliable means to quantify the broad range of pathologies that potentially develop very early in autoimmune optic neuritis. Tissue microfluorimetry was used to measure seven established markers for human MS pathology in normal and autoimmune optic nerves 13 days after antigen exposure, in a Brown Norway rat model of myelin oligodendrocyte glycoprotein (MOG) peptide (35-55)-induced autoimmune optic neuritis. Optic neuritis rats demonstrated early and significant pathologic changes in five established indices for neuroinflammation, immune infiltration, and demyelination that accurately modeled pathologies characteristic of MS. Two indices of MS-like axon damage advanced significantly within 13 days of antigen exposure. Fluorimetrically measured immunoreactivity (-ir) was significantly decreased for paranodin (PN, the requisite axonal paranodal junction protein) and significantly increased for amyloid precursor protein (APP), indicating loss of paranodal junctions and impaired fast axonal transport, respectively. Measurements showing decreased PN ir with increased APP-ir quantitatively defined a pattern of early axonal damage in autoimmune optic neuritis. PMID- 17719650 TI - Peritraumatic tonic immobility predicts a poor response to pharmacological treatment in victims of urban violence with PTSD. AB - INTRODUCTION: Tonic immobility is the last defense against predation in animals and is characterized by paralysis and analgesia. In humans, it has only been reported in women victims of sexual abuse. OBJECTIVE: This study evaluated the prevalence of peritraumatic tonic immobility (PTI) in patients with PTSD and investigated its association with response to treatment. METHOD: Victims of urban violence with PTSD diagnosed through the SCID-IV (n=23) underwent a naturalistic pharmacological treatment according to the recommended guidelines for PTSD. The Post-Traumatic Stress Disorder Checklist--Civilian Version (PCL-C) and the Clinical Global Impressions (CGI) Severity scores were applied at baseline and endpoint. PTI was assessed using the Tonic Immobility Scale. RESULTS: PTI was reported by both genders in 43% of the sample. Patients with PTI responded significantly poorly to treatment than those without it, either considering the PCL-C or the CGI scores. LIMITATIONS: This study probed PTI retrospectively and was based on a small sample recruited in a tertiary clinic. CONCLUSIONS: We have expanded the scope of the two previous investigations on PTI by showing its occurrence also in men and during non-sexual violence. In addition, the finding of a significant relationship between PTI and poor response to treatment of PTSD indicates that PTI may carry a prognostic value in this disorder and suggests that PTI should be routinely assessed in traumatized patients. PMID- 17719651 TI - Alternative activation of ruminant macrophages by Fasciola hepatica. AB - The helminth parasite, Fasciola hepatica, has a worldwide distribution and infects a wide variety of mammalian hosts, including ruminants and man. In response to infection, these hosts mount a type 2 helper (Th2) response that is highly polarized and results in the downregulation of type 1 helper (Th1) mechanisms. In a murine macrophage model F. hepatica induces alternative activation of macrophages. These macrophages differ from classically activated cells in that they preferentially use arginase instead of inducible nitric oxide synthase (iNOS) for metabolism of nitrogen. In this study we sought to characterize macrophage phenotype following stimulation of the ovine cell line MOCL7 with recombinant F. hepatica enzymes and crude parasite extracts. An in vitro model using the MOCL7 cell line was established and arginase levels in cells were used to determine the activation status of cells. Stimulation of this cell-line in vitro with F. hepatica products induces alternative activation. We have also found a chitinase-like protein in supernatants which is capable of differentiating alternatively activated from classically activated macrophages. PMID- 17719652 TI - Expression of complement regulatory proteins on human natural killer cell subsets. AB - The cell surface complement regulatory (CReg) proteins CD46, CD55 and CD59 are widely distributed on human leucocytes and protect against complement-mediated damage. To investigate heterogeneity in CReg protein expression by human natural killer (NK) cells, levels were assessed on resting and activated NK cell subsets identified phenotypically on the basis of expression of CD56 and CD158 markers. Levels of all three CReg proteins on CD56+ cells were lower than on T cells (p<0.05). Freshly isolated CD56(bright) cells expressed higher levels of CD55 than CD56dim cells (p<0.05). CD158a+ cells expressed significantly lower levels of both CD46 and CD59, and CD158e+ cells expressed significantly lower levels of CD46, than CD158a(-) CD158e(-) cells, respectively (both p<0.05). Stimulation with PHA did not significantly alter NK cell surface CReg protein levels whereas, following culture with IL-2, CD46 and CD59 were decreased on both CD56bright and CD56dim subsets (p<0.05). In the case of CD59, this was independent of T cells. Only CD46 was significantly downregulated on CD158b+ (GL183+) and CD158e (NKB1+) subsets (p<0.05). However, culture in IL-15 significantly increased levels of all three CReg proteins. These observations that CReg proteins are downregulated on certain NK cell subsets following activation with IL-2 are opposite to previous findings for other leucocyte subpopulations. Activated NK cells may instead use other strategies for protection against complement-mediated damage in a local inflammatory response. PMID- 17719653 TI - Intracellular JNK, p38 MAPK and NF-kappaB regulate IL-25 induced release of cytokines and chemokines from costimulated T helper lymphocytes. AB - Novel Th2 cytokine IL-25 has been shown to be elevated in allergic inflammation. We investigated the intracellular mechanisms regulating IL-25-induced Th2 cytokines and chemokines from human Th lymphocytes upon costimulation by anti-CD3 and anti-CD28 antibodies. Cytokines, chemokines, and phosphorylated p38 mitogen activated protein kinases (MAPK), c-Jun amino-terminal kinase (JNK) and extracellular signal-regulated protein kinase were analyzed by bead-based array using flow cytometry. Nuclear factor (NF)-kappaB and total MAPK were assessed by electrophoretic mobility shift assay and Western blot, respectively. IL-25 could synergistically induce the release of Th2 cytokines IL-4, IL-5 and IL-10, inflammatory cytokine IL-6, Th1 related chemokines CXCL9 and CXCL10, and chemokine CCL5 from anti-CD3 and anti-CD28 antibodies costimulated Th cells, especially memory Th cells. Costimulation could also upregulate the cell surface expression of IL-25 receptor on Th cells. Costimulation with or without IL-25 treatment could activate JNK, p38 MAPK and NF-kappaB. The upregulation of costimulation-induced IL-25 receptors and release of cytokines and chemokines from IL-25 treated costimulated Th cells were differentially regulated by intracellular JNK, p38 MAPK and NF-kappaB activity. Therefore, the optimal activation of Th cells by IL-25 for the release of Th2 cytokines and chemokines requires the CD3 and CD28 mediated costimulation of Th cells via the upregulation of IL-25 receptors and the activation of intracellular signaling pathways. This mechanistic study shows that IL-25 and CD28 costimulation can play pathophysiological roles by inducing inflammation and hyperresponsiveness through the production of both Th2 cytokines and chemokines from memory Th cells. PMID- 17719654 TI - The therapeutic effect of glatiramer acetate in a murine model of inflammatory bowel disease is mediated by anti-inflammatory T-cells. AB - Inflammatory bowel diseases (IBDs) are complex multifactorial immunological disorders characterized by dysregulated immune reactivity in the gut and imbalance between pro-inflammatory and anti-inflammatory reactivity. The therapeutic effect of the immunomodulatory drug glatiramer acetate (GA, Copaxone, copolymer 1) has been established in several IBD models, including trinitrobenzene sulfonic acid (TNBS) and dextran sulfate sodium (DSS)-induced colitis, as well as in a spontaneous colitis model. In the present study we investigated the mechanism of action of GA and cells specifically induced by it. Immunization of naive mice by GA, generated a lymphocyte population of the Th2/3 subtype, that drastically reduced disease manifestations upon their adoptive transfer to mice with DSS colitis. This was demonstrated by the substantial decrease in weight loss, intestinal bleeding and diarrhea, as well as by the prevention of macroscopic and microscopic colonic damage. In contrast, adoptive transfer of control lysozyme-specific cells did not induce any beneficial effect on the disease. Moreover, GA-specific short-term T-cell lines, either exogenously labeled or genetically marked, adoptively transferred by the intraperitoneal route to colitis-induced mice, localized in the inner layers of the colon and secreted in situ the regulatory cytokine TGF-beta. These results demonstrate the accumulation of GA-specific Th2/3 cells secreting regulatory cytokines in the injured colon, and thus draw a direct linkage between the therapeutic effect of GA in IBD and an immunomodulatory effect at the site in which the pathological process occurs. PMID- 17719655 TI - Brain endothelial PPARgamma controls inflammation-induced CD4+ T cell adhesion and transmigration in vitro. AB - An important step in the pathogenesis of multiple sclerosis is adhesion and transmigration of encephalitogenic T cells across brain endothelial cells (EC) which strongly relies on interaction with EC-expressed adhesion molecules. We provide molecular evidence that the transcription factor peroxisome proliferator activated receptor gamma (PPARgamma) is a negative regulator of brain EC inflammation. The PPARgamma agonist pioglitazone reduces transendothelial migration of encephalitogenic T cells across TNFalpha-stimulated brain EC. This effect is clearly PPARgamma mediated, as lentiviral PPARgamma overexpression in brain EC results in selective abrogation of inflammation-induced ICAM-1 and VCAM 1 upregulation and subsequent adhesion and transmigration of T cells. We therefore propose that PPARgamma in brain EC may be exploited to target detrimental EC-T cell interactions under inflammatory conditions. PMID- 17719656 TI - Optimized protocol for the large scale production of HIV pseudovirions by transient transfection of HEK293T cells with linear fully deacylated polyethylenimine. AB - HIV vaccine strategies which employ pseudovirions (PVs) as the source of antigen require large amounts of particles. These are typically generated by transient transfection of mammalian cells and purification of the released PVs from the culture supernatant. Since efficiency and cost of transfection are key issues, in this report the transfection efficiencies, achieved by employing a panel of high molecular-weight linear polyethylenimines (PEIs) and small cross-linked PEIs, were analyzed and compared to those obtained by transfections with calcium phosphate or the commercial reagent Polyfect. High efficiencies were obtained using several of the modified PEIs, and the transfections with these inexpensive reagents were very robust. The observed efficiencies (as quantitated by amounts of expressed gene product) were two to four fold superior to calcium phosphate transfection and approximately equal to that achieved using Polyfect which is, however, prohibitively expensive for large scale applications. An optimized and rapid protocol for the large scale production and purification of HIV-PVs from 293T cells growing in so-called cell stacks and transfected with the best reagent identified, PEI87, is described here. The generated PVs, obtained with a yield in the range of 0.4mg virion-associated HIV-CA/liter culture supernatant, exhibited only very minimal contamination with non-viral proteins and were thus suitable for vaccination applications. PMID- 17719657 TI - Effective small interfering RNAs targeting matrix and nucleocapsid protein gene inhibit influenza A virus replication in cells and mice. AB - RNA interference (RNAi) is a powerful tool to silence gene expression. Small interfering RNA (siRNA)-induced RNA degradation has been recently used as an antivirus agent to inhibit specific virus replication. Here, we showed that several siRNAs specific for conserved regions of influenza virus matrix (M2) and nucleocapsid protein (NP) genes could effectively inhibit expression of the corresponding viral protein. We also evaluated the antiviral potential of these siRNAs targeting M2 and NP of H5N1 avian influenza virus (AIV), which are essential to viral replication. We investigated the inhibitory effect of M2 specific siRNAs and NP-specific siRNAs on influenza A virus (H5N1, H1N1 and H9N2) replication in Madin-Darby canine kidney (MDCK) cells and BALB/c mice. The results showed that treatment with these siRNAs could specifically inhibit influenza A virus replication in MDCK cells (0.51-1.63 TCID(50) reduction in virus titers), and delivery of pS-M48 and pS-NP1383 significantly reduced lung virus titers in the infected mice (16-50-fold reduction in lung virus titers) and partially protected the mice from lethal influenza virus challenge (a survival rate of 4/8 for H1N1 virus-infected mice and 2/8 for H5N1 virus infected mice). Moreover, the treatment of pS-M48 and pS-NP1383 could suppress replication of different subtypes of influenza A viruses, including a H5N1 highly pathogenic avian isolate strain. The results provided a basis for further development of siRNA for prophylaxis and therapy of influenza virus infection in humans and animals. PMID- 17719658 TI - Variant proteins of the Plasmodium falciparum RIFIN family show distinct subcellular localization and developmental expression patterns. AB - In order to avoid immune recognition in favor of a chronic infection, the malaria parasite Plasmodium falciparum has developed means to express clonally variant antigens at the surface of the infected erythrocyte (IE). Proteins of the var and rif multicopy gene families, encoding PfEMP1 and RIFINs, respectively, have been implicated in these processes. Here, we studied members of the latter family and present data revealing different subcellular localization patterns for RIFIN variants belonging to two distinct subgroups, which have been designated A- and B type RIFINs. While A-type RIFINs were found to be associated with the parasite and transported to the surface of infected erythrocytes via Maurer's clefts, B type RIFINs appeared to be mostly retained inside the parasite. However, expression of both subtypes does not seem to be mutually exclusive. Moreover, both A- and B-type variants were also expressed in the merozoite, present either in the apical region (A-type) or in the cytosol (B-type). The presence of RIFINs in merozoites suggests that antigenic variation in P. falciparum is not only restricted to parasite-derived proteins at the IE surface, but the phenomenon also prevails in other life cycle stages. Interestingly, some RIFIN variants were detected only in intracellular stages and not in merozoites, pointing to differential developmental expression patterns for distinct members of this large protein family. PMID- 17719659 TI - Combined anterior and inferior ST segment elevation during the exercise stress testing. AB - Exercise induced ST elevation, especially in anterior derivations, does localize the ischemic region. We describe a patient who presented with exercise induced ST elevation in both anterior and inferior leads without prior myocardial infarction. Coronary angiography showed a "wrap around LAD" with significant proximal lesion. PMID- 17719660 TI - Takayasu arteritis evaluated by multi-slice computed tomography in an old man. AB - In the case of patients with Takayasu arteritis (TA), they consult a doctor for the first time when they have a slight fever, shoulder pain, chest pain, back pain, or headache, or when they are pointed out to have high CRP or anemia by chance in medical check-up. In TA, they are usually young women. In our case, the very old patient had bilateral massive pleural effusion and aortic aneurysm with a 64-slice computed tomography (CT). TA commonly affects primarily large elastic arteries such as the aorta and its main branches. Steroid was very effective for suppression of inflammatory symptom being dose-dependent. His pleural effusion had been decreasing without reducing the size of aortic aneurysm. Multi-slice CT was a very useful tool to detect unexpected lesion in Takayasu arteritis in a non invasive manner. PMID- 17719661 TI - Acute ST-elevation myocardial infarction secondary to paradoxical embolism. AB - Acute ST-elevation myocardial infarction (STEMI) is a life threatening condition usually caused by rupture of an atheromatous plaque in the coronary arteries. Other causes, such as septic emboli, cholesterol emboli and cocaine abuse have been reported. We report a case of acute STEMI in a young female without any vascular risk factors due to a presumptive paradoxical embolism via a secundum atrial septal defect (ASD). Young patients without vascular risk factors presenting with acute myocardial infarction should be investigated to exclude an underlying cause of their myocardial infarction, such as a paradoxical embolus. PMID- 17719662 TI - Activation of interleukin-1 beta (IL-1 beta) signaling in the spinal cord in the rats with experimental cardiac injury. AB - BACKGROUND: The involvement of central nervous system (CNS) interleukin-1 beta (IL-1 beta) in the pathogenesis of acute cardiac injury is still an unexplored issue. The present study was aimed to investigate whether cardiac injury could induce the activation of IL-1 beta in the spinal cord. METHODS AND RESULTS: Cardiac injury model in rats was established by intra-myocardial injection of formalin through the diaphragm. Western blot showed that IL-1 beta was upregulated in the upper thoracic spinal cord following cardiac injury. The upregulated IL-1 beta was distributed in the dorsal and ventral horns in the thoracic spinal cord as determined by immunohistochemistry. In situ hybridization demonstrated that IL-1 beta mRNA localized in the neurons was elevated in response to cardiac injury. The DNA binding activities of two IL-1 beta transcription factors, activator protein (AP)-1 and nuclear factor kappa B (NF kappaB), were enhanced after cardiac injury. In correlated with the upregulation of the spinal IL-1 beta, the circulating IL-1 beta level was also increased following cardiac injury. CONCLUSIONS: Acute cardiac injury could activate the spinal IL-1 beta signaling, which, in turn, may contribute to disease progression in the acute phase of cardiac injury in clinical practice. PMID- 17719663 TI - Head to head comparison of transesophageal and transthoracic contrast-enhanced echocardiography during dobutamine administration for the detection of coronary artery disease. AB - Dobutamine stress echocardiography (DSE) has been shown to be a very useful non invasive technique for the detection of coronary artery disease. However, inadequate transthoracic images preclude the use of DSE in a significant proportion of patients. Transesophageal (TEE) or transthoracic contrast echocardiography (CE) can however overcome this limitation. The comparison between the two techniques has never been investigated during a stress test. Therefore, we designed a prospective study to compare DSE-CE and DSE-TEE for the detection of coronary artery disease in patients with poor echo image quality. We studied 42 patients scheduled for quantitative coronary angiography. Prospective DSE-CE and DSE-TEE with maximum one day interval were performed in a random order. Significant coronary artery disease was detected in 30 patients, nine with single vessel disease and 21 with multivessel disease. Sensitivity of DSE was higher with CE than with TEE (90% vs 87%, p=NS). There was no significant difference with respect to specificity in both groups (100% vs 92%, p=NS). The diagnostic accuracy was similar in both groups (93% vs 88%, NS). The kappa value for identical interpretation of a stress echocardiography study was nearly identical with both modalities 0.75 to 0.78. In poorly echogenic patients, DSE-CE is a valuable alternative for the detection of myocardial ischemia in comparison with DSE-TEE. Because DSE-CE is more comfortable than TEE, it should be used in patients with suboptimal transthoracic echocardiograms for the evaluation of coronary artery disease during DSE. PMID- 17719664 TI - Occurrence of anthelmintic resistant equine cyathostome populations in central and southern Italy. AB - In the present survey, 276 horses bred on 16 farms located in central and southern Italy were investigated for the presence of drug resistant cyathostomes by a Fecal Egg Count Reduction Test (FECRT). Sixteen to 20 animals were selected on each farm and randomly assigned to one of four equally sized treatment groups. Groups were treated with fenbendazole, pyrantel pamoate, ivermectin or moxidectin. Resistance to fenbendazole was declared on six farms (37.5%) and suspected in two farms (12.5%), with FECR values ranging from 41% to 88.3%. Resistance to pyrantel was found in two farms (12.5%) and was suspected in one case (6.2%), with FECR values ranging from 43% to 85.4%. Macrocyclic lactones remained effective on all farms. Only cyathostome third stage larvae (L3) were found in fecal cultures after treatment. This paper reports the first wide survey conducted in Italy for anthelmintic resistance in equine cyathostomes. The results indicate that multiple drug resistant equine cyathostomes are present in the central and southern regions of Italy. These data call for a geographically and numerically broader investigation of horse farms in all regions and for the development and implementation -among veterinarians, owners and managers of a plan to reduce the expansion of these anthelmintic resistant populations and control these important parasites. PMID- 17719665 TI - A high-throughput and generic assay method for the determination of substrate specificities of thermophilic alpha-aminotransferases. AB - For the determination of substrate specificities of thermophilic alpha aminotransferases (AATs), a novel high-throughput assay method was developed. In this method, a thermophilic omega-aminotransferase (OAT) and a thermophilic aldehyde dehydrogenase (ALDH) are coupled to the AAT reaction. Glutamic acid is used as an amino group donor for the AAT reaction yielding 2-oxoglutalic acid. 2 Oxoglutalic acid produced by the AAT reaction is used as an amino group acceptor in the OAT reaction regenerating glutamic acid. The amino group donor of the OAT reaction is 5-aminopentanoic acid yielding pentanedioic acid semialdehyde which is oxidized by ALDH to pentanedioic acid with concomitant reduction of NADP(+) to NADPH. NADPH thus produced then reduces colorless tetrazolium salt into colored formazan. To construct such a reaction system, the genes for a thermophilic AAT, a thermophilic OAT and a thermophilic ALDH were cloned and expressed in Escherichia coli. These enzymes were subsequently purified and used to determine the activities of AAT for the synthesis of unnatural amino acids. This method allowed the clear detection of the AAT activities as it measures the increase in the absorbance on a low background absorbance reading. PMID- 17719666 TI - Application of the hsp65 PRA method for the rapid identification of mycobacteria isolated from clinical samples in Belgium. AB - Biochemical identification of mycobacteria is slow and many times fail to produce correct results. We compared PCR-restriction fragment length polymorphism analysis (PRA) of hsp65 and biochemical methods for the identification of mycobacteria from human samples in Belgium. PRA was found useful in the identification of mycobacteria and simple to implement as a quick method in the laboratory. PMID- 17719667 TI - Alternatives to antibiotics to control bacterial infections: luminescent vibriosis in aquaculture as an example. AB - The massive (mis)use of antibiotics to control infections in aquaculture has resulted in the development of resistant strains, which have rendered antibiotic treatments ineffective. Moreover, the horizontal transfer of resistance determinants to human pathogens and the presence of antibiotic residues in aquaculture products for human consumption constitute important threats to public health. Therefore, to make the aquaculture industry more sustainable, new strategies to control infections are urgently needed. PMID- 17719668 TI - Anatomical bases for the radiological delineation of lymph node areas. Upper limbs, chest and abdomen. AB - Cancer spreads locally through direct infiltration into soft tissues, or at distance by invading vascular structures, then migrating through the lymphatic or blood flow. Although cancer cells carried in the blood can end in virtually any corner of the body, lymphatic migration is usually stepwise, through successive nodal stops, which can temporarily delay further progression. In radiotherapy, irradiation of lymphatic paths relevant to the localisation of the primary has been common practice for decades. Similarly, excision of cancer is often completed by lymphatic dissection. Both in radiotherapy and in surgery, advanced knowledge of the lymphatic pathways relevant to any tumour location is an important information for treatment preparation and execution. This second part describes the lymphatics of the upper limb, of the thorax and of the upper abdomen. Providing anatomical bases for the radiological delineation of lymph nodes areas in the axilla, in the chest and in the abdomen, it also offers a simplified classification for labeling the mediastinal and intra-abdominal nodal levels, grouped in each location inside three major functional areas (called I, II and III) which are all divided into three sublevels (named a, b or c). PMID- 17719669 TI - Behaviours of log phase cultures of eight strains of Escherichia coli incubated at temperatures of 2, 6, 8 and 10 degrees C. AB - The behaviours of cold-adapted, log-phase cultures of eight strains of Escherichia coli incubated at 2, 6, 8 and 10 degrees C for 10 days were examined by determining absorbance at 600 nm (A(600)), viable counts and cell size distribution as indicated by forward angle light scattering (FALS) values, obtained for samples collected each day from each culture. Cell lengths were determined from photomicrographs of samples for which the flow cytometry data indicated the mean cell lengths were maximal or minimal for each culture. At 2 degrees C, A(600) values for all strains and viable counts for some changed little, while viable counts for other strains declined progressively by >1 log unit. At 6 degrees C, A(600) values for most strains increased at progressively declining rates and then remained constant while viable counts increased to reach maximum values before maximum A(600) values were attained, and then declined. At 8 degrees C, the behaviours of most strains were similar to the behaviour at 6 degrees C. At 10 degrees C, seven of the strains grew exponentially, but for most of these the growth rate determined from A(600) values differed from that determined from viable count data. Mean FALS values for cultures incubated at 6, 8, or 10 degrees C showed various patterns of increase and decrease, indicating fluctuations in cell lengths. For all strains, the minimum cell length was <3 microm, but the maximum cell lengths ranged from <20 to >140 microm. The findings suggest that the formation of elongated cells or filaments is usual behaviour for E. coli growing at temperatures approaching or below the minimum for sustained growth. PMID- 17719670 TI - Establishment of procedures provoking sub-lethal injury of Listeria monocytogenes, Campylobacter jejuni and Escherichia coli O157 to serve method performance testing. AB - In this study procedures provoking sub-lethal injury for three different pathogens are described which may be used in determination of accuracy and robustness of methods, comparison studies and or validation of rapid detection methods. Three common food-borne pathogens were used, Listeria monocytogenes, Campylobacter jejuni and Escherichia coli O157. The pathogens were exposed to heat stress, cold stress, freeze stress, acid stress, oxidative stress and "food" stress. Sub-lethal injury was determined by plating in parallel on selective and non-selective media. The statistical significant differences in enumeration were established. The choice of stress to create sub-lethal injury to cells depended on the fact that the procedure must be easy to handle, repeatable and relevant for stress conditions in foods, but also on the micro-organism itself. Oxidative stress (1000 microM H(2)O(2)) was chosen to impose sub-lethal injury on L. monocytogenes and a specific "food" stress for E. coli O157. For C. jejuni a specific "food" stress as well as the oxidative stress (750 microM H(2)O(2)) were capable of creating a standardized procedure of provoking injury. PMID- 17719671 TI - Protective action of Lactobacillus kefir carrying S-layer protein against Salmonella enterica serovar Enteritidis. AB - Eight Lactobacillus kefir strains isolated from different kefir grains were tested for their ability to antagonize Salmonella enterica serovar Enteritidis (Salmonella enteritidis) interaction with epithelial cells. L. kefir surface properties such as autoaggregation and coaggregation with Salmonella and adhesion to Caco-2/TC-7 cells were evaluated. L. kefir strains showed significantly different adhesion capacities, six strains were able to autoaggregate and four strains coaggregated with Salmonella. Coincubation of Salmonella with coaggregating L. kefir strains significantly decreased its capacity to adhere to and to invade Caco-2/TC-7 cells. This was not observed with non coaggregating L. kefir strains. Spent culture supernatants of L. kefir contain significant amounts of S-layer proteins. Salmonella pretreated with spent culture supernatants (pH 4.5-4.7) from all tested L. kefir strains showed a significant decrease in association and invasion to Caco-2/TC-7 cells. Artificially acidified MRS containing lactic acid to a final concentration and pH equivalent to lactobacilli spent culture supernatants did not show any protective action. Pretreatment of this pathogen with spent culture supernatants reduced microvilli disorganization produced by Salmonella. In addition, Salmonella pretreated with S-layer proteins extracted from coaggregating and non coaggregating L. kefir strains were unable to invade Caco-2/TC-7 cells. After treatment, L. kefir S-layer protein was detected associated with Salmonella, suggesting a protective role of this protein on association and invasion. PMID- 17719672 TI - Evaluation of Newcastle disease virus chimeras expressing the Hemagglutinin Neuraminidase protein of velogenic strains in the context of a mesogenic recombinant virus backbone. AB - A major factor in the pathogenicity of Newcastle disease virus (NDV) is the amino acid sequence of the fusion protein cleavage site, but the role of other viral genes that contribute to virulence and different clinical forms of the disease remain undefined. To assess the role of other NDV genes in virus pathogenicity, a reverse genetics system was developed using the mesogenic NDV Anhinga strain to provide a backbone for generating gene mutations or gene exchanges in attempts to enhance or attenuate the virulence of that virus. Chimeras created by exchange of the Anhinga Hemagglutinin-Neuraminidase (HN) gene with HN genes of neurotropic and viscerotropic velogenic viruses produced no significant change in virus pathogenicity as assessed by conducting the mean death time and intracerebral pathogenicity index assays and by inoculation of susceptible day-old SPF chickens. Inclusion in the recombinant construct of homotypic F genes, obtained from the parental viruses, also failed to enhance the pathotype of the recombinant viruses to a velogenic pathotype. A HN gene exchange alone within the context of the NDV Anhinga backbone failed to increase virus virulence from mesogenic to velogenic pathotype and suggests a multigenic role for NDV pathogenicity. PMID- 17719673 TI - Extraction of information on elder motor ability from clinical and biomechanical data through data mining. AB - This study aimed at evaluating the additional knowledge provided by a biomechanical test coupled with clinical tests for motor ability assessment. A database including clinical test scores and sit-to-stand test variables obtained from 110 medically stable elderly subjects was submitted to data mining by searching for association rules. The presence of rules revealed some redundancies due to sample homogeneity, as mainly observed in the joint analysis of a questionnaire for daily activities assessment (Nottingham test) and the sit-to stand, and due to similar evaluated information, as resulted from the joint analysis of a balance and gait scale (Tinetti test) and the sit-to-stand. Conversely, when no association rules were found, the tests carried unrelated information. The associations mined while analysing these clinical tests encouraged the integration of biomechanical tests, increasing significantly its clinical applicability and reducing the information redundancy. The information extracted also allowed to highlight rules typical of elderly persons that may serve as a knowledge-based tool for the detection of possible deviation from normality. PMID- 17719674 TI - Identification and reliability of microbial aerobic respiration and denitrification kinetics using a single-well push-pull field test. AB - Methods to derive reaction rates of microbial processes are important since these processes are determining many chemical reactions influencing groundwater quality. Thereby, it is not only important to derive the parameters, but also to have a firm idea about the reliability with which these are determined. Analysis of residuals, sensitivity analyses and analysis of joint confidence intervals provide an interesting tool for this purpose. The method is illustrated in this paper using a push-pull test designed to derive aerobic respiration and denitrification. Therefore, a test solution containing dissolved oxygen and nitrate as reactive tracer and bromide as non-reactive tracer was injected in organic matter rich sediment. Afterwards, this test solution was extracted and water quality was monitored. ReacTrans, a finite-difference, axial-symmetric groundwater flow and solute transport model was developed to simulate the test and derive hydraulic, solute transport and chemical parameters. Aerobic respiration and denitrification were simulated with Michaelis-Menten kinetics. Maximum reaction rates (10.4 and 2.4 mmol/ld for aerobic respiration and denitrification respectively) and Michaelis constants (0.14 and 0.1 mmol/l for aerobic respiration and denitrification respectively) were determined. The reliability with which these parameters are derived is indicated by analysis of residuals, sensitivities and joint confidence intervals. This shows that the Michaelis-Menten parameters can be derived reliable with a push-pull test, whereas the test is insensitive to effective porosity and hydraulic conductivity. Because of the small scale of the test, longitudinal dispersivity was very small and therefore unidentifiable. PMID- 17719676 TI - Presentation and outcome of purpura fulminans associated with peripheral gangrene in 12 patients at Mayo Clinic. AB - BACKGROUND: Dermatologists may be called to assist in the diagnosis and management of purpura fulminans. METHODS: This retrospective case series details the clinical presentation and outcomes of patients presenting with purpura fulminans associated with peripheral gangrene between 1989 and 2004. RESULTS: All 12 patients presented with sudden onset of purpuric patches and evolving gangrene of the extremities in association with a shock syndrome (hypotension, oliguria). Eleven patients had disseminated intravascular coagulation. The cause of purpura fulminans was infectious in 9 patients, surgical in two, and cancer in one. Three patients died (25%) within a week of onset of purpura fulminans. Of the 9 surviving patients, 8 required amputation of at least one limb. Four patients required amputation of all 4 limbs. LIMITATIONS: Retrospective study design, varying clinical descriptions, and potential referral bias are limitations. CONCLUSION: Purpura fulminans in association with symmetric peripheral gangrene is an ominous clinical presentation. PMID- 17719677 TI - Is binge eating experienced as an addiction? AB - To ascertain to what degree binge eating is experienced as an addiction, this study examined the proportion of women with binge-eating disorder (BED) whose symptoms met criteria for an addiction. Women (N = 79) with current BED completed a structured telephone interview to assess for symptoms of a modified version of DSM-IV substance dependence and Goodman's [(1990). Addiction: Definition and implications. British Journal of Addiction, 85, 1403-1408] proposed diagnosis of 'addictive disorder'. Most binge eaters (92.4%) met modified DSM-IV criteria for substance dependence, whereas many fewer (40.5%) met Goodman's more restrictive criteria for addictive disorder. Women meeting criteria for addictive disorder had more frequent eating binges than those who did not. Despite certain observed similarities between binge eating and addictions, we argue that BED should remain classified as an eating disorder. PMID- 17719678 TI - Clinical epidemiology and outcomes of peripheral venous catheter-related bloodstream infections at a university-affiliated hospital. AB - Despite enormous clinical experience of using peripheral vascular catheters, there is still controversy over the incidence and clinical relevance of bloodstream infections caused by these devices and the measures for preventing them. We performed a prospective study to determine the clinical epidemiology and outcomes of nosocomial bloodstream infections caused by short- and mid-line peripheral venous catheters among a group of non-intensive care unit patients. Cases of peripheral venous catheter-related bloodstream infections (PVC-BSIs) were compared to cases of central venous catheter-related bloodstream infections (CVC-BSIs). From October 2001 to March 2003, 150 cases of vascular catheter related bloodstream infections were identified among 147 patients. Seventy-seven episodes (0.19 cases/1000 patient-days) were PVC-BSIs and 73 episodes (0.18 cases/1000 patient-days) were CVC-BSIs. Compared with CVC-BSIs, patients with PVC BSIs more often had the catheter inserted in the emergency department (0 vs 42%), had a shorter duration from catheter insertion to bacteraemia (mean: 15.4 vs 4.9 days) and had Staphylococcus aureus (33 vs 53%) more frequently as the causative pathogen. Among patients with PVC-BSIs, catheters inserted in the emergency department had a significantly shorter duration in situ compared with those inserted on hospital wards (mean: 3.7 vs 5.7 days). Patients with PVC-BSIs caused by S. aureus had a higher rate of complicated bacteraemia (7%) and higher overall mortality (27%) than patients with PVC-BSIs caused by other pathogens (0 and 11%, respectively). Bloodstream infections remain underestimated and potentially serious complications of peripheral vascular catheterisation. Targeted interventions should be introduced to minimise this complication. PMID- 17719679 TI - Clinical course and outcome of a nosocomial outbreak of hepatitis C in a urology ward. AB - This paper describes a prospective study of the clinical course and outcome of a nosocomial outbreak of hepatitis C virus (HCV) infection in six male urology patients at a hospital in Stara Zagora, Bulgaria. These patients had been previously hospitalised in the urology ward, during which all had received intravenous therapy. Approximately three weeks later, all six were admitted to the infectious diseases unit with acute hepatitis, shown to be caused by HCV genotype 1b. The diagnosis was confirmed by polymerase chain reaction during the first week of their hospital stay. Infected patients were followed up for 30 months following diagnosis and 54 potential contacts for 6 months post-exposure. Four patients recovered completely; one developed chronic HCV infection and one died. The latter already had cirrhosis due to co-infection with hepatitis B virus. The investigation established the index case as a patient with chronic hepatitis C, who had been an in-patient on the same ward at the same time. The most likely route of transmission was intravenous heparin flushes administered with a common syringe. Contrary to the common assumption that acute HCV infection often leads to chronic disease, only one chronic case was observed during the 30 month period of investigation. PMID- 17719680 TI - Prevalence and risk factors for MRSA in adult emergency admissions: a case for screening all patients? PMID- 17719681 TI - Ten-year air sample analysis of Aspergillus prevalence in a university hospital. AB - Airborne fungal samples were collected on a monthly basis for 10 years, from 1995 to 2005, at a tertiary university hospital. Paired samples were cultured at 25 and 37 degrees C. Data were interpreted according to the air filtration systems serving each location. Samples cultured at 37 degrees C from the patient care areas had a mean recovery of 18% of the mean recovery from outdoor air (22 versus 122cfu/m(3)). Recovery of Aspergillus spp. at 37 degrees C in the high-efficiency particulate air (HEPA)-filtered locations was positive for Aspergillus spp. approximately one-third of the time; the rest of the patient care areas were positive half of the time and the outdoor samples were positive 95% of the time. We found 48 sporadic bursts at 37 degrees C which produced counts >3 SD above the mean. Hospital-acquired infection was related to high recovery of Aspergillus fumigatus on at least one occasion. We have found it impossible, without implementing impractical measures, to provide an environment completely devoid of Aspergillus spp. We conclude that routine air sampling is not an effective means of predicting hospital-acquired infections. However, a transient spike, or burst, may be useful in identifying an in-house source of contamination and may be used to consider additional interventional treatments for patients at risk. Emphasis should be placed on maintaining high-efficiency filtration of the outside air and on ensuring that other environmental control methods are used to prevent dissemination of environmental opportunistic fungal spores. PMID- 17719682 TI - Bloodstream infection related to catheter connections: a prospective trial of two connection systems. AB - Bloodstream infections (BSIs) related to central venous catheters (CVCs) and arterial catheters (ACs) are an increasing problem in the management of critically ill patients. Our objective was to assess the efficacy of a needle free valve connection system (SmartSite), Alaris Medical Systems, San Diego, CA, USA) in the prevention of catheter-related bloodstream infection (CR-BSI). Patients admitted to an intensive care unit were prospectively assigned to have a CVC and AC connected with either a needle-free valve connection system (NFVCS) or a three-way stopcock connection (3WSC). The characteristics of the patients were similar in the two groups. Before manipulation, the NFVCS was disinfected with chlorhexidine digluconate 0.5% alcoholic solution. The 3WSC was not disinfected between use but it was covered with a protection cap. A total of 799 patients requiring the insertion of a multilumen CVC or AC for >48h from 1 April 2002 to 31 December 2003 were included. CR-BSI rates were 4.61 per 1000 days of catheter use in the disinfected NFVCS group and 4.11 per 1000 days of catheter use in the 3WSC group (P=0.59). When CVC-BSIs and AC-BSIs were analysed separately, the rate of CVC-BSI was 4.26 per 1000 days of catheter use in the NFVCS group, compared with 5.27 in the 3WSC group (P=0.4). The incidence rate of AC-BSI was 5.00 per 1000 days of catheter use in the NFVCS group, compared with 2.83 in the 3WSC group (P=0.08). The use of NFVCS does not reduce the incidence of catheter related bacteraemia. The arterial catheter (AC) is a significant source of infection in critically ill patients. PMID- 17719683 TI - Group B streptococcal colonisation in pregnant women: turnaround time of three culture methods. PMID- 17719684 TI - Outbreak of multi-resistant Corynebacterium striatum infection in an Italian general intensive care unit. PMID- 17719685 TI - 'My five moments for hand hygiene': a user-centred design approach to understand, train, monitor and report hand hygiene. AB - Hand hygiene is a core element of patient safety for the prevention of healthcare associated infections and the spread of antimicrobial resistance. Its promotion represents a challenge that requires a multi-modal strategy using a clear, robust and simple conceptual framework. The World Health Organization First Global Patient Safety Challenge 'Clean Care is Safer Care' has expanded educational and promotional tools developed initially for the Swiss national hand hygiene campaign for worldwide use. Development methodology involved a user-centred design approach incorporating strategies of human factors engineering, cognitive behaviour science and elements of social marketing, followed by an iterative prototype test phase within the target population. This research resulted in a concept called 'My five moments for hand hygiene'. It describes the fundamental reference points for healthcare workers (HCWs) in a time-space framework and designates the moments when hand hygiene is required to effectively interrupt microbial transmission during the care sequence. The concept applies to a wide range of patient care activities and healthcare settings. It proposes a unified vision for trainers, observers and HCWs that should facilitate education, minimize inter-individual variation and resource use, and increase adherence. 'My five moments for hand hygiene' bridges the gap between scientific evidence and daily health practice and provides a solid basis to understand, teach, monitor and report hand hygiene practices. PMID- 17719686 TI - An outbreak of Halomonas phocaeensis sp. nov. bacteraemia in a neonatal intensive care unit. AB - Unidentified Gram-negative aerobic rods were recovered from the blood cultures of six neonates in a neonatal intensive care facility in Tunis, Tunisia. 16S rRNA gene sequencing showed that these were members of the Halomonas genus, with <97% sequence similarity to their closest relative. The observation of unique phenotypic characteristics of these organisms supported a novel species and the name Halomonas phocaeensis sp. nov. was proposed. A case-control study and conditional logistic regression analysis suggested that the administration of fresh frozen plasma was the only independent risk factor for developing H. phocaeensis bacteraemia. Observational studies indicated that fresh frozen plasma was warmed up using a water-bath. This first description of a nosocomial outbreak of H. phocaeensis bacteraemia illustrates the infection risks associated with poorly controlled water hygiene in healthcare settings. PMID- 17719687 TI - Rapid detection of MRSA in a routine diagnostic laboratory using a real-time PCR assay. PMID- 17719688 TI - Emergency physician activation of the cath lab: saving time, saving lives. PMID- 17719689 TI - Physiological effects of a conducted electrical weapon on human subjects. AB - STUDY OBJECTIVE: Sudden death after a conducted electrical weapon exposure has not been well studied. We examine the effects of a single Taser exposure on markers of physiologic stress in healthy humans. METHODS: This is a prospective trial investigating the effects of a single Taser exposure. As part of their police training, 32 healthy law enforcement officers received a 5-second Taser electrical discharge. Measures before and for 60 minutes after an exposure included minute ventilation; tidal volume; respiratory rate (RR); end-tidal PCO2; oxygen saturation, pulse rate; blood pressure (systolic blood pressure/diastolic blood pressure); arterialized blood for pH, PO2, PCO2, and lactate; and venous blood for bicarbonate and electrolytes. Troponin I was measured at 6 hours. Data were analyzed using a repeated-measures ANOVA and paired t tests. RESULTS: At 1 minute postexposure, minute ventilation increased from a mean of 16 to 29 L/minute, tidal volume increased from 0.9 to 1.4 L, and RR increased from 19 to 23 breaths/min, all returning to baseline at 10 min. Pulse rate of 102 beats/min and systolic blood pressure of 139 mm Hg were higher before Taser exposure than at anytime afterward. Blood lactate increased from 1.4 mmol/L at baseline to 2.8 mmol/L at 1 minute, returning to baseline at 30 minutes. pH And bicarbonate decreased, respectively, by 0.03 and 1.2 mEq/L at 1 minute, returning to baseline at 30 minutes. All troponin I values were normal and there were no EKG changes. Ventilation was not interrupted, and there was no hypoxemia or hypercarbia. CONCLUSION: A 5-second exposure of a Taser X26 to healthy law enforcement personnel does not result in clinically significant changes of physiologic stress. PMID- 17719690 TI - Initial test of emergency procedure performance in temporary negative pressure isolation by using simulation technologies. AB - STUDY OBJECTIVE: The potential of infectious disease spread in diseases such as tuberculosis, infectious disease epidemic such as avian flu and the threat of terrorism with agents capable of airborne transmission have focused attention on the need for increased surge capacity for patient isolation. Total negative pressure isolation using portable bioisolation tents may provide a solution. The study assesses the ability of health care workers to perform emergency procedures in this environment. METHODS: Physician performance in completing predetermined critical actions in 5 emergency care scenarios inside and outside of a bioisolation tent ("setting") was studied in an advanced medical simulation laboratory. By design, no pretraining of subjects about total negative pressure isolation use occurred. Impact of setting on time to completion of predetermined critical actions was the primary outcome measured. Secondary variables studied included impact of study groups, scenarios, and run order (inside or outside of the tent first). Subjective assessments were obtained through questionnaires. RESULTS: Four teams of 3 physicians completed 5 emergency patient care scenarios during 2 4-hour sessions. Mean time to completion of critical actions was for tent/no tent 298 seconds/284 seconds (P=.69, one way ANOVA), respectively. Mean time to completion for first versus second performance of a scenario in the crossover design was 338 versus 243 (P=.01). The mean score for self-assessed performance did not differ according to setting. CONCLUSION: The ability of physicians naive to the total negative pressure isolation environment to perform emergency medical critical actions was not significantly degraded by a simulated bioisolation tent patient care environment. PMID- 17719691 TI - Truth, and epinephrine, at our fingertips: unveiling the pseudoaxioms. PMID- 17719692 TI - To sit or not to sit: a question of cultural performance. PMID- 17719693 TI - All that wheezes is not obstructive pulmonary disease. PMID- 17719694 TI - Turnaround time and transaction costs. PMID- 17719695 TI - The discovery of VIP: initially looked for in the lung, isolated from intestine, and identified as a neuropeptide. PMID- 17719696 TI - Localization, characterization and function of pituitary adenylate cyclase activating polypeptide during brain development. AB - Neural development is controlled by region-specific factors that regulate cell proliferation, migration and differentiation. Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide that exerts a wide range of effects on different cell types in the brain as early as the fetal stage. Here we review current knowledge concerning several aspects of PACAP expression in embryonic and neonatal neural tissue: (i) the distribution of PACAP and PACAP receptors mRNA in the developing brain; (ii) the characteristic generation of neurons, astrocytes and oligodendrocytes in brain areas where the PACAP receptor is expressed and (iii) the role of PACAP as a regulator of neural development, inducing differentiation and proliferation in association with other trophic factors or signal transduction molecules. PMID- 17719697 TI - PACAP: the road to discovery. PMID- 17719698 TI - Neurosecretases provide strategies to treat sporadic and familial Alzheimer disorders. AB - Recent discoveries on neurosecretases and their trafficking to release fibril forming neuropeptides or other products, are of interest to pathology, cell signaling and drug discovery. Nomenclature arose from the use of amyloid precursor protein (APP) as a prototypic type-1 substrate leading to the isolation of beta-secretase (BACE), multimeric complexes (gamma-secretase, gamma-SC) for intramembranal cleavage, and attributing a new function to well-characterized metalloproteases of the ADAM family (alpha-secretase) for normal APP turnover. While purified alpha/beta-secretases facilitate drug discovery, gamma-SC presents greater challenges for characterization and mechanisms of catalysis. The review comments on links between mutation or polymorphisms in relation to enzyme mechanisms and disease. The association between lipoprotein receptor LRP11 variants and sporadic Alzheimer's disease (SAD) offers scope to integrate components of pre- and post-Golgi membranes, or brain clathrin-coated vesicles within pathways for trafficking as targets for intervention. The presence of APP and metabolites in brain clathrin-coated vesicles as significant cargo with lipoproteins and adaptors focuses attention as targets for therapeutic intervention. This overview emphasizes the importance to develop new therapies targeting neurosecretases to treat a major neurological disorder that has vast economic and social implications. PMID- 17719699 TI - Effect of novel arecoline thiazolidinones as muscarinic receptor 1 agonist in Alzheimer's dementia models. AB - The discovery of cholinergic deficit in Alzheimer's disease (AD) patient's brain has triggered research efforts, using cholinomimetic approaches for their efficacy in AD therapy. Various therapies may be of potential clinical use in AD. Among these are cholinergic agents, which include muscarinic agonists, acetylcholinesterase inhibitors, and acetylcholine releasing agents. One of the muscarinic agonists tested in AD is arecoline and its bioisosters, which are widely explored as muscarinic receptor 1 agonist (M1 receptor agonist) in AD research. In this regard, five-membered heterocyclic ring system attached arecoline basic nucleus (N-methyl tetrahydropyridines) at third position has been extensively researched on. The present research involved synthesis of arecoline thiazolidinones 5(a-j) by using dipolar addition of 3-aminopyridine and alkyl/aryl carboxaldehydes in presence of gamma ferrite as catalyst. The resulting products were methylated and reduced to get desired products. Subsequently the synthesized arecoline thiazolidinones were subjected to in vitro muscarinic receptor binding studies using male Wistar rat brain (cerebral cortex) membrane homogenate and extended this in vitro study to in vivo pharmacological evaluation of memory and learning in male Wistar rats. Four derivatives (5a-5c and 5e) showed considerable M1 receptor binding affinity (in vitro) and elicited beneficial effects in vivo memory and learning models (Rodent memory evaluation, plus and Y maze studies). PMID- 17719700 TI - Peptidyl 3-substituted 1-hydroxyureas as isosteric analogues of succinylhydroxamate MMP inhibitors. AB - To evaluate N-hydroxyurea as zinc binding group in the design of MMP inhibitors, two peptidyl 1-hydroxyureas were prepared by N-hydroxycarbamoylation of the diastereomeric dipeptides H-Leu-Phe-NHMe and H-D-Leu-Phe-NHMe. Peptidyl 1 hydroxyureas were more potent than the parent peptides, but dramatically weaker (4-5 orders of magnitude) than the isosteric (R)-succinylhydroxamate analogue, which displays IC(50) in the range of nM vs MMP-1, -3, -7 and sub-nM vs MMP-2, 8, and -9. The peptidyl 1-hydroxyurea 1a attained an IC(50) of 20 microM vs MMP 9, and substantially approaches inhibition of known N-hydroxyureas based on aminoacids or peptides against other zinc metalloenzymes and non-peptidic N hydroxyureas against MMPs. Strong preference of the O-N1-C=O unit for the antiperiplanar amide bond conformation seems to be the major limit for more effective zinc chelation. Methylation of a peptidyl 1-hydroxyurea at N3, to promote the synperiplanar O-N1-C=O conformation required for zinc chelation and improve affinity, resulted in release of a methylimidazolidine-2,4-dione through an undesired intramolecular reaction reminiscent of the Edman peptide degradation. PMID- 17719701 TI - Celiac disease: in vitro and in vivo safety and palatability of wheat-free sorghum food products. AB - BACKGROUND & AIMS: Celiac disease is a condition in which genetically predisposed people have an autoimmune reaction to gluten proteins found in all wheat types and closely related cereals such as barley and rye. This reaction causes the formation of autoantibodies and the destruction of the villi in the small intestine, which results in malabsorption of nutrientsand other gluten-induced autoimmune diseases. Sorghum is a cereal grain with potential to be developed into an important crop for human food products. The flour produced from white sorghum hybrids is light in color and has a bland, neutral taste that does not impart unusual colors or flavors to food products. These attributes make it desirable for use in wheat-free food products. While sorghum is considered as a safe food for celiac patients, primarily due to its relationship to maize, no direct testing has been conducted on its safety for gluten intolerance. Therefore studies are needed to assess its safety and tolerability in celiac patients. Thus the aim of the present study was to assess safety and tolerability of sorghum flour products in adult celiac disease patients, utilizing an in vitro and in vivo challenge. RESULTS: Sorghum protein digests did not elicit any morphometric or immunomediated alteration of duodenal explants from celiac patients. Patients fed daily for 5 days with sorghum-derived food product did not experience gastrointestinal or non-gastrointestinal symptoms and the level of anti transglutaminase antibodies was unmodified at the end of the 5-days challenge. CONCLUSIONS: Sorghum-derived products did not show toxicity for celiac patients in both in vitro and in vivo challenge. Therefore sorghum can be considered safe for people with celiac disease. PMID- 17719702 TI - The effect of a combination of plant sterol-enriched foods in mildly hypercholesterolemic subjects. AB - BACKGROUND & AIMS: The purpose of this study was to evaluate the effect of low fat products enriched with plant sterols in addition to a National Cholesterol Education Program step 1 diet on serum lipids and lipoproteins. METHODS: This study was a double-blind, randomised, placebo-controlled cross-over design with a run-in period and 2 intervention periods, each lasting 4 weeks. A total of 46 mildly hypercholesterolemic subjects (age 50.6+/-9.8) completed the trial. The study products consisted of 20 g low-fat margarine (35% fat) and 250 ml low-fat milk (0.7% fat), in total delivering 2.3g plant sterols/d. RESULTS: Serum total and low-density lipoprotein cholesterol were significantly reduced by 5.5% (p<0.001, 95% CI: 2.5; 8.3) and 7.7% (p=0.001, 95% CI: 3.4; 11.9), respectively, by plant sterol-enriched products compared to placebo. Serum apolipoprotein B was significantly reduced by 4.6% (p<0.05, 95% CI: 1.7; 7.5), and apolipoprotein B/apolipoprotein A-I by 3.4% (p<0.05, 95% CI: 0.1; 6.6) after plant sterol intake compared to the placebo supplement. CONCLUSIONS: A combination of low-fat margarine and milk enriched with plant sterols significantly reduced low-density lipoprotein cholesterol, apolipoprotein B and the ratio of apolipoprotein B to apolipoprotein A-I in mildly hypercholesterolemic subjects, but had no effect on C-reactive protein and lipoprotein (a) concentrations. SPONSORSHIP: Unilever Denmark A/S. PMID- 17719705 TI - A process-based model for the partitioning of soluble, suspended particulate and bed sediment fractions of plutonium and caesium in the eastern Irish Sea. AB - A dynamic model of plutonium behaviour in the marine environment has been developed, representing the oxidation state distribution and partitioning of plutonium between the soluble, colloidal, suspended particulate and seabed sediment fractions. With simple re-parameterisation, this model can also be applied to (137)Cs. The model, which is calibrated and validated against field data, has been used to predict concentrations of Pu(alpha) and (137)Cs in both water and seabed sediments from the vicinity of the Sellafield Ltd. reprocessing plant in Cumbria, UK. The model predicts that sediment reworking and transport are the key environmental processes as the Sellafield Pu(alpha) and (137)Cs discharge continues to decline. Inventory calculations generated by the model are consistent with previous estimations. For a hypothetical post-discharge scenario, the concentrations of these radionuclides in both seawater and surface sediments are predicted to decrease sharply, concurrent with a downward vertical migration of the activity retained in sediments. PMID- 17719703 TI - Immediate oral feeding in patients with mild acute pancreatitis is safe and may accelerate recovery--a randomized clinical study. AB - BACKGROUND & AIMS: In acute pancreatitis, traditional treatment has been initial fasting on purpose to avoid activation of proteolytic enzymes and pancreatic enzyme secretion. The aim of the present study was to evaluate the efficacy and feasibility of immediate oral feeding as compared to traditional fasting in patients with mild acute pancreatitis. METHODS: Sixty patients were randomized to the two treatment groups, fasting or immediate oral feeding. The inclusion criteria were pancreas amylase > or =3 times above normal, onset of abdominal pain within 48 h, acute physiological and chronic health evaluation (APACHE) score<8 and C-reactive protein (CRP) <150 mg/L. Outcome measures were pancreas specific amylase, systemic inflammatory response, feasibility and length of hospital stay (LOHS). RESULTS: The groups were comparable with respect to age, sex, etiology, APACHE, time from onset of pain and amylase at admission. No significant differences were seen between the groups concerning levels of amylase, CRP, leukocytes, abdominal pain or number of gastrointestinal symptoms. The LOHS was significantly shorter in the oral feeding group (4 vs. 6 days; p<0.05). CONCLUSIONS: No signs of exacerbation of the disease process were seen in terms of significant differences between treatment groups for amylase or systemic inflammatory response. In mild acute pancreatitis, immediate oral feeding was feasible and safe and may accelerate recovery without adverse gastrointestinal events. PMID- 17719706 TI - Spontaneous alignment of permanent successors after enucleation of odontogenic cysts associated with primary teeth. AB - Pulpotomy and pulpectomy occasionally lead to cyst formation in the primary dentition. They show specific clinical features of large size, rapid growth, buccal expansion and displacement of permanent teeth. Complete enucleation of the cyst with extraction of the associated primary teeth and preservation of the permanent teeth appeared to be the most suitable treatment option. Normal alignment of the permanent teeth occurred spontaneously even their initial positions were highly unfavourable. PMID- 17719707 TI - Bioaccumulation behaviour of transplants of the lichen Flavoparmelia caperata in relation to total deposition at a polluted location in Portugal. AB - This experiment compares the short and long time element accumulation behaviour of transplants of Flavoparmelia caperata lichen thalli and total deposition in an atmospheric polluted area. It was found that lichens exposed for a short time behaved differently from lichens in cumulative exposition suggesting the presence of acclimatization behaviour. The lichen transplant elemental content does not unequivocally represent the average or cumulative environmental availability of the exposure period. Reflection characteristics depend on the element and the lichen physiological conditions. Good correlations between lichen elemental contents and total deposition were obtained when a physiological lichen parameter was introduced in a mathematical model, suggesting that metabolically mediated accumulation is important. PMID- 17719708 TI - A quackery with a difference-new medical pluralism and the problem of 'dangerous practitioners' in the United Kingdom. AB - The figure of the 'miracle cure'-peddling quack pretending spectacular properties for worthless tonics is iconic. From their 19th century traveling wagon shows to their 21st century Internet spam scams, hucksters and cranks have been consistently targeted by health authorities as a danger to public health. Yet, in this paper, I argue that this is only one form that the problem of 'quackery' has taken in the past two centuries or so in the United Kingdom. Just as Roy Porter showed how the mid-19th century professionalization of medicine gave rise to a 'quackery with a difference' as a whole range of new medical movements homoeopathy, hydropathy, medical botany, mesmerism-actively denounced allopathic or modern medicine, I will suggest that the late 20th century birth of 'complementary and alternative medicine' (CAM) has resulted in yet another transformation in quackery. By examining the ways in which regulatory authorities in the UK have come to address what is invariably described as a 'growing interest in CAM', I will show how the problem of quackery today is increasingly located in an ethical field of practitioner competency, qualifications, conduct, responsibility and personal professional development, almost (but not quite) regardless of the form of therapy in question. PMID- 17719709 TI - Locality deprivation and Type 2 diabetes incidence: a local test of relative inequalities. AB - There is increasing evidence that the socio-spatial context of the local area in which one lives can have an effect on health, but teasing out contextual influences is not a simple task. We examine whether the incidence of Type 2 diabetes in small areas in Tayside, Scotland is associated with deprivation in neighbouring areas, controlling for the deprivation of the area itself. As such, this is a genuinely 'contextual' variable situating each small area in the context of surrounding places. We test two opposing hypotheses. First, a 'psycho social' hypothesis might suggest that negative social comparisons made by individuals in relation to those who surround them could lead to chronic low level stress via psycho-social pathways, the physiological effects of which could promote diabetes. Thus, we would expect people living in deprived areas surrounded by less deprived areas to have an increased risk of diabetes, compared to those living in similarly deprived areas that are surrounded by equally or more deprived areas. Alternatively, a neo-materialist approach might suggest that the social, cultural and environmental resources in the surrounding environment will influence circumstances in a particular area of interest. Poorer areas surrounded by less deprived areas would benefit from the better resources in the wider locality, while less deprived areas surrounded by poorer areas may be hampered by the poorer resources available nearby. We refer to this as the 'pull up/pull-down' hypothesis. Our results show that, as expected, area deprivation is positively related to diabetes incidence (p<0.001), whilst deprivation inequality between areas and their neighbours is negatively related (p=0.006). Type 2 diabetes is more common in deprived areas, but lower in deprived areas that are surrounded by relatively less deprived areas. On the other hand, less deprived areas that are surrounded by relatively more deprived areas have higher diabetes incidence than would be expected from the deprivation of the area alone. Our model results are consistent with a pull-up/pull-down model and lend no support to a 'psycho-social' interpretation at this local scale of analysis. PMID- 17719710 TI - Knowing before we know: conscious versus preconscious top-down processing and a neuroscience of intuition. PMID- 17719711 TI - [Mediatisation and "facial graft" or "to whom belongs the facial graft"?]. AB - Mediatisation of a scientific event could be neither controlled, nor verifiable. The experience which has been lived through the first worldwide allotransplantation of composite tissues of the face confirms that the actors of a surgical innovation are not the owners. Because there is neither confidentiality nor possible patent. Curiously the scientific world, providing with a sharing ethic, which rightly privileges the free spreading of knowledge in the way that most people could benefit of it. Obviously it is made without denied controversy, for truth as purpose. This scientific word that way joins the media one, with a specific ethic of the duty of information, but also interested in mercantile preoccupations quick to cultivate controversy not to enlighten this truth but to better sell pictures or papers. Than the author should only sustain this instrumentation which could certainly flatter him, and from which he could used, but in reality that paralysed him a little to go on in serenity with his shadow worker way. PMID- 17719712 TI - [Philosophical and ethics aspects of the composite tissues allotransplantations (CTA)]. AB - The first successes of total hand and partial face transplants raise several philosophical and ethical questions. This paper examines the perspective of the recipient, the donor and the social aspect. The question of the identity remains unsolved. Philosophical point of view shows an historical continuity in the desire of the human being for improving his condition. PMID- 17719713 TI - ["Facial graft": about the first facial allotransplantation of composite tissues]. AB - The first facial allograft was realised in Amiens 2005 November 27th. Breaking the technical limits of the so called possible and in appearance transgressing some cultural forbidden in organ transplantation, this resolutely innovative intervention open more than new perspective in the surgery of the reconstruction after disfigurement, but also a wide field of scientific investigations about dynamic and meaning of the facial function. Obviously, it also deals with numerous ethical and medical problems. The authors here shortly described the technical points of the surgery firstly done to restore oral function and facial expressively, the principles of the immunosuppressive treatment built to control any rejection time episode and the anatomical, neurological and functional results obtained after more than 18 months follow-up. Those perfectly demonstrate the perfect morphological, dynamic and cortical integration of the graft in the recomposed face. They also allow to confirm the legitimacy of the surgical indication and to oppose the factual objective arguments to the ethical reticences dealing with the facial and psychological identity of the receptor. PMID- 17719714 TI - [Social and anthropology considerations on the composite tissues allotransplantations (CTA). Excerpts from reading and analysis of a surgeon]. AB - The author is neither anthropologist nor invested in social activities. He has learned some reviews of anthropology and some social and philosophical books since seven years. He describe not a general review but an analysis of these lectures according to the composite tissues allotransplantations (CTA). The discussion concerns anthropology and symbols, philosophical and social aspects. There is a natural umbilicus between the anthropological science and the surgical art according to CTA. PMID- 17719715 TI - [Reconstruction of the nasal alar defect with the superiorly based nasolabial flap described by Burget: report of seven cases]. AB - BACKGROUND: The reconstitution of a nasal alar rim and lobule defect represent a difficult challenge in consideration of his situation, anatomy and function. This article describes the technique and the interest of the nasolabial flap when used to cover the entire alar subunit. METHODS: We present 7 cases of alar rim and lobule defect after skin cancer excision. In the series, there are two full thickness with lining defect. The patients were reconstructed with a superiorly based nasolabial flap, according to the subunit principle as introduced by Burget. A free cartilage graft was used to restore structural support with marginal skin flaps were turned over for intranasal lining when necessary. RESULTS: The cosmetic and functional outcomes of each repair were judged from good to excellent by patients and surgeons. No case of flap infection or necrosis occurred. CONCLUSION: The superiorly based nasolabial flap, describe by Burget, provides an excellent choice for cosmetic and functional reconstruction of the nasal alar defect. PMID- 17719716 TI - Editors' highlights. PMID- 17719717 TI - A new and integrated hydro-economic accounting and analytical framework for water resources: a case study for North China. AB - Water is a critical issue in China for a variety of reasons. China is poor of water resources with 2,300 m(3) of per capita availability, which is less than 13 of the world average. This is exacerbated by regional differences; e.g. North China's water availability is only about 271 m(3) of per capita value, which is only 125 of the world's average. Furthermore, pollution contributes to water scarcity and is a major source for diseases, particularly for the poor. The Ministry of Hydrology [1997. China's Regional Water Bullets. Water Resource and Hydro-power Publishing House, Beijing, China] reports that about 65-80% of rivers in North China no longer support any economic activities. Previous studies have emphasized the amount of water withdrawn but rarely take water quality into consideration. The quality of the return flows usually changes; the water quality being lower than the water flows that entered the production process initially. It is especially important to measure the impacts of wastewater to the hydro ecosystem. Thus, water consumption should not only account for the amount of water inputs but also the amount of water contaminated in the hydro-ecosystem by the discharged wastewater. In this paper we present a new accounting and analytical approach based on economic input-output modelling combined with a mass balanced hydrological model that links interactions in the economic system with interactions in the hydrological system. We thus follow the tradition of integrated economic-ecologic input-output modelling. Our hydro-economic accounting framework and analysis tool allows tracking water consumption on the input side, water pollution leaving the economic system and water flows passing through the hydrological system thus enabling us to deal with water resources of different qualities. Following this method, the results illustrate that North China requires 96% of its annual available water, including both water inputs for the economy and contaminated water that is ineligible for any uses. PMID- 17719718 TI - Editorial comment on: Laparoscopic extended pelvic lymph node dissection for prostate cancer: description of the surgical technique and initial results. PMID- 17719719 TI - Editorial comment on: Laparoscopic extended pelvic lymph node dissection for prostate cancer: description of the surgical technique and initial results. PMID- 17719720 TI - Risk factors of young ischemic stroke in Qatar. AB - OBJECTIVES: There is limited information about risk factors of young ischemic stroke in Qatar. The aim of this study was to describe the risk factors and subtypes of young ischemic stroke among Qatari and non-Qatari residents. PATIENTS AND METHODS: Hospital based prospective observational study involving all young adults (15-45 years of age) admitted to Hamad General Hospital with first-ever ischemic stroke from September 2004 to September 2005. A stroke was defined according to WHO criteria. RESULTS: Stroke was confirmed in 40 (32 males and 8 females). Their ages ranged from 17 to 44 years (mean 37.1+/-13.27). Thirty (75%) of the patients were non-Qatari. The most common risk factors were hypertension 16 (40%), diabetes mellitus 13 (32.5%), hypercholesterolemia 11 (27.5%), smoking 11 (27.5%), and alcohol intake 9 (22.5%). Regarding stroke subtypes, lacunar stroke syndrome (LACS) was diagnosed in 17 (42.5%), total anterior circulation stroke syndrome (TACS) in 16 (40%), partial anterior circulation stroke syndrome (PACS) in 5 (12.5%) and posterior circulation stroke syndrome (POCS) in 2 (5%). Partial anterior circulation stroke syndrome (PACS) was observed with a higher frequency in Qatari patients compared with non-Qataris (p=0.009), whereas total anterior circulation stroke syndrome (TACS) was observed more in non-Qatari than in Qatari patients (p=0.03). Average hospital stay was 18 days. In-hospital mortality was 2.5%. CONCLUSION: The risk factors of ischemic stroke in young adults are numerous. The most common were hypertension, diabetes mellitus, hypercholesterolemia, smoking and alcohol intake. Only one Indonesian male patient with POCS died in the hospital. PMID- 17719721 TI - Ischemic stroke in a child mistaken as functional disorder. AB - Stroke is a rare but increasingly recognized disorder in children. Lack of published clinical trials and experience in most institutions has resulted in significant challenges for clinicians who manage children with stroke. We report a case of 16-year-old male child who was presented with history of sudden onset of weakness 2 months back and before he could consult the physician, the weakness improved significantly and a misdiagnosis of functional disorder was made at a peripheral hospital. Children with stroke may have subtle manifestations and to make an early diagnosis of stroke in children there is need of awareness about this entity in children. PMID- 17719722 TI - Cooperative activation of Src family kinases by SH3 and SH2 ligands. AB - Src family nonreceptor tyrosine kinases are kept in a repressed state by intramolecular interactions involving the SH3 and SH2 domains of the enzymes. Ligands for these domains can displace the intramolecular associations and activate the kinases. Here, we carried out in vitro activation experiments with purified, down-regulated hematopoietic cell kinase (Hck), a Src family kinase. We show that SH3 and SH2 ligands act cooperatively to activate Src family kinases: the presence of one ligand lowers the concentration of the second ligand necessary for activation. To confirm the findings in intact cells, we studied Cas, a Src substrate that possesses SH2 and SH3 ligands. In contrast to wild-type Cas, mutant forms of Cas lacking the SH3 or SH2 ligands were unable to stimulate Src autophosphorylation when expressed in Cas-deficient fibroblasts. Cells expressing the Cas mutants also showed decreased amounts of activated Src at focal adhesions. The results suggest that proteins containing ligands for both SH3 and SH2 domains can produce a synergistic activation of Src family kinases. PMID- 17719723 TI - Effect of effluent generated from coffee processing plant on the water bodies and human health in its vicinity. AB - The objective of this study was to assess the effect of wastewater produced from coffee processing plant on nearby water bodies and human health. A study was conducted around the coffee processing plant in Zimma zone (Ethiopia) to assess the physico-chemical characteristics of effluent generated from this plant. Analysis of the water samples taken from the surrounding water bodies had also been done. It was found, from the present investigation, that the wastewater from coffee processing plant was heavily polluted with organic matter as it showed high concentration of COD (upstream 25,600mg/l and downstream 15,780mg/l), BOD (upstream 14,200mg/l and downstream 10,800mg/l), phosphate (upstream 7.3mg/l and downstream 4.6mg/l), nitrate (upstream 23mg/l and downstream 10.5mg/l) and suspended solids (upstream 5870mg/l and downstream 2080mg/l) and these concentrations were much higher than the permissible limits prescribed by WHO. It was also found, from this study, that the people residing in the vicinity of this plant were consuming this polluted water and as a result suffered from many diseases like skin irritation, stomach problem, nausea and breathing problem. PMID- 17719724 TI - Misperceptions of peer drinking norms in Canada: another look at the "reign of error" and its consequences among college students. AB - OBJECTIVE: Much research has documented extensive misperceptions of drinking norms and their negative effects in U.S. student populations. This study provides extensive research evidence documenting this phenomenon in Canadian higher education. METHODS: Data were collected in a 2003-2004 survey of students (N=5280) attending 11 institutions across Canada. Surveys were administered either to a random sample of students through the mail or to students attending a diverse selection of classes. RESULTS: Regardless of the actual drinking norm on each campus, students most commonly overestimated the alcohol consumption norms (both quantity and frequency levels) in every instance. Students' perception of their campus drinking norm was the strongest predictor of the amount of alcohol personally consumed in comparison with the influence of all demographic variables. Perception of the norm was also a much stronger predictor of personal use than the actual campus norm for consumption on each campus or the actual norm for compliance with campus regulations. Among students who personally abstain or consume lightly, misperceptions of the student drinking norms contribute to alienation from campus life. CONCLUSION: The data presented here on Canadian students extends the evidence that peer drinking norms are grossly misperceived and that these misperceptions produce a highly detrimental "reign of error" in the lives of college students. The data suggest that a broad range of students- abstainers and light drinkers as well as moderate and heavy drinkers--may benefit from implementing intervention strategies that can correct or reduce these misperceptions. PMID- 17719725 TI - Munchausen syndrome by proxy: more than "economic vested interests". PMID- 17719726 TI - [Comments on: "Post-partum compliance to oral glucose tolerance test" (n(o) 3/2007)]. PMID- 17719727 TI - Safety, tolerability and subject-rated effects of acute intranasal cocaine administration during atomoxetine maintenance. AB - The results of recent research indicate that agonist replacement may be a viable option in the treatment of cocaine dependence. For example, d-amphetamine and modafinil have shown promise in managing cocaine dependence in preliminary clinical trials. The aim of this study was to determine the physiological and subject-rated effects of acute intranasal cocaine doses during chronic atomoxetine treatment. Atomoxetine was chosen because it produces pharmacological and subject-rated effects similar to those of prototypical stimulants and thus may also be a viable agonist replacement therapy. To this end, seven cocaine dependent subjects were maintained on doses of atomoxetine (0mg [lead in], 5, 10, 20 and 0mg [washout], four times daily) for 3-5 days prior to completing experimental sessions in which ascending doses of intranasal cocaine (4, 20, 40 and 60 mg) were administered. Cocaine produced prototypical cardiovascular and subject-rated effects. Atomoxetine attenuated the systolic pressure increasing effects and enhanced the heart rate increasing effects of cocaine, but was otherwise devoid of effects. These results indicate that cocaine is well tolerated during atomoxetine maintenance. Further research is needed to better determine the effects of atomoxetine and cocaine combinations. PMID- 17719729 TI - Molecular epidemiology of bovine toroviruses circulating in South Korea. AB - The prevalence of the bovine torovirus (BToV) and its genetic characterization have been reported in North America, Europe and Japan. Therefore, this study examined the prevalence and genetic diversity of the BToV in a total of 645 diarrheic fecal samples from 629 Korean native beef calf herds using RT-PCR and nested PCR with the primer pairs specific to a part of the BToV membrane (M) gene. Overall, 19 (2.9%) out of 645 diarrheic samples from 19 herds (6.9%) tested positive for BToVs by either RT-PCR or nested PCR. A comparison of the nucleotide (nt) and amino acid (aa) sequences of a part of the BToV M gene (409bp) among the BToVs showed the Korean BToVs to have comparatively higher sequence homology to the Japanese and Dutch BToVs than to the American and Italian BToVs. Generally, the Korean BToV strains clustered with the Japanese and Dutch BToV strains. However, the American and Italian BToV strains clustered on a separate major branch, suggesting that these are more distantly related to other known BToV strains. These results suggest that the BToV infections are sporadic in diarrheic calves in South Korea, and the Korean BToV strains are more closely related to the Japanese and Dutch BToVs than to the American and Italian BToVs. PMID- 17719728 TI - Structural characteristics of zebrafish orthologs of adaptor molecules that associate with transmembrane immune receptors. AB - Transmembrane bound receptors comprised of extracellular immunoglobulin (Ig) or lectin domains play integral roles in a large number of immune functions including inhibitory and activating responses. The function of many of the activating receptors requires a physical interaction with an adaptor protein possessing a cytoplasmic regulatory motif. The partnering of an activating receptor with an adaptor protein relies on complementary charged residues in the two transmembrane domains. The mammalian natural killer (NK) and Fc receptors (FcR) represent two of many receptor families, which possess activating receptors that partner with adaptor proteins for signaling. Zebrafish represent a powerful experimental model for understanding developmental regulation at early stages of embryogenesis and for efficiently generating transgenic animals. In an effort to understand developmental aspects of immune receptor function, we have accessed the partially annotated zebrafish genome to identify six different adaptor molecules: Dap10, Dap12, Cd3zeta, Cd3zeta-like, FcRgamma and FcRgamma-like that are homologous to those effecting immune function in mammals. Their genomic organizations have been characterized, cDNA transcripts have been recovered, phylogenetic relationships have been defined and their cell lineage-specific expression patterns have been established. PMID- 17719731 TI - Herpes virus inhibitory substances from Hypericum connatum Lam., a plant used in southern Brazil to treat oral lesions. AB - Hypericum connatum (Guttiferae) is used in southern Brazil in the treatment of lesions in the mouth, often related to acute herpetic gingivo-stomatitis. The chemical investigation of the plant revealed the presence of phloroglucinol derivatives and flavonoids. From the n-hexane extract of the aerial parts a phloroglucinol derivative, hyperbrasilol B, was isolated, while the methanolic extract afforded four flavonoids: amentoflavone, hyperoside, guaijaverine and luteoforol. The crude methanolic extract and fractions (n-hexane, dichloromethane and methanol) as well as the isolated compounds were tested for antiviral activity against herpes simplex viruses (HSV). Among the tested samples, luteoforol was the most active inhibiting the cytopathic effect (CPE) and reducing the viral titer of HSV-1 DNA viral strains KOS and VR733 (ATCC). PMID- 17719730 TI - The distribution of esterases in the skin of the minipig. AB - Skin esterases serve an important pharmacological function as they can be utilised for activation of topically applied ester prodrugs. Understanding the nature of these enzymes, with respect to their role and local activity, is essential to defining the efficacy of ester prodrugs. Minipigs are used as models to study the kinetics of absorption of topically applied drugs. Their skin has structural properties very similar to human skin. However, regional distribution differences in esterase activity from site-to-site could influence cross-species extrapolation. Investigation of the regional site variation of minipig skin esterase activity will facilitate standardization of topically applied drug studies. Furthermore, the characterization of regional skin variation, will aid in translation of minipig results to better predictions of human esterase activity. Here we report the variation in rates of hydrolysis by minipig skin taken from different regional sites, using the esterase-selective substrates: phenyl valerate (carboxylesterase), phenyl acetate (arylesterase) and p nitrophenyl acetate (general esterase). Skin from ears and back of male minipig showed higher activity than female. Skin from minipig ears and the back showed the highest level of esterase activity and was similar to human breast skin used in vitro absorption studies. These results suggest that skin from the minipig back is an appropriate model for preclinical human skin studies, particularly breast skin. This study supports the use of the minipig, with topical application to the back, as a model for the investigation of pharmacokinetics and metabolism of ester prodrugs. PMID- 17719732 TI - Inhibitory effect of processed Aconiti tuber on the development of antinociceptive tolerance to morphine: evaluation with a thermal assay. AB - In the previous studies, we demonstrated that an oriental herbal medicine processed Aconiti tuber (PAT) at subanalgesic doses could inhibit the development of mechanical antinociceptive tolerance to morphine using the tail pressure test. In the present study, we evaluated whether PAT could inhibit thermal antinociceptive tolerance to morphine using the high temperature (55 degrees C) hot plate test. Mice received subcutaneous morphine (10mg/kg), and oral PAT at doses that did not inhibit the hot plate response (0.3, 0.5, 1.0, and 2.0 g/kg), once daily for 14 days. The thermal nociceptive latency was measured at 30 min after daily morphine injections. Compared with placebo, oral PAT partially and dose-dependently inhibited the development of morphine tolerance in morphine naive mice, and reversed already-developed morphine tolerance in morphine tolerant mice. These data suggested that PAT at subanalgesic doses could dose dependently inhibit and reverse thermal antinociceptive tolerance to morphine. PMID- 17719733 TI - The time-dependent expressions of IL-1beta, COX-2, MCP-1 mRNA in skin wounds of rabbits. AB - In this study, we investigated the time-dependent expression of IL-1beta, COX-2, MCP-1 mRNA after incised wounds in rabbit skin using real-time fluorescent quantitative PCR. The tested wound ages were distributed as following: <0.5h, 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 2d, 3d, and 7d. The expressions of three markers in postmortem wounds were determined. Comparison of each wound age with control group, expression of IL-1beta mRNA showed that the significant increase occurred at <0.5h (p<0.01), and the peak level at 2h. The expression was almost normalized at 2d. But for COX-2 and MCP-1 mRNA, the significant increase occurred at 1h for COX-2 mRNA, and 3h for MCP-1 mRNA. The expression peak levels were at 3h and 5h, and were almost normalized at 3d and 7d, respectively. There was no significant increase in all postmortem samples for IL-1beta, COX-2, MCP-1 mRNA compared with control group. Thus, the results of these cytokines and enzyme significant increase at different early wound ages implied that the combined investigation could make wound age determination more objective and accurate. Moreover, the three markers could also be used to distinguish the supravital injuries. PMID- 17719734 TI - Contrast-enhanced versus systematic transrectal ultrasound-guided prostate cancer detection: an overview of techniques and a systematic review. AB - An overview is given of the current conventional and contrast-specific transrectal ultrasound (TRUS) techniques for prostate imaging that may be used for guiding biopsy. Subsequently, a systematic literature search resulted in inclusion of four studies that directly compared systematic and contrast-enhanced targeted TRUS-guided biopsy of the prostate. All four studies revealed that contrast-enhanced-targeted TRUS-guided biopsy significantly improved the positive biopsy core rate. In the largest study, the mean Gleason score of the contrast enhanced-targeted TRUS-guided biopsies was significantly higher than that of the systematic biopsies. Future randomized clinical trials, preferably in a non academic multi-institutional set-up, will have to be performed to confirm the value of contrast-enhanced-targeted TRUS-guided biopsy in regular clinical practice. PMID- 17719735 TI - Development and validation of an automated solid-phase extraction and liquid chromatographic method for determination of lumefantrine in capillary blood on sampling paper. AB - A bioanalytical method for the determination of lumefantrine in 100 microl blood applied onto sampling paper, by solid-phase extraction and liquid chromatography, has been developed and validated. Whatman 31 ET Chr sampling paper was pre treated with 0.75 M tartaric acid before sampling capillary blood to enable a high recovery of lumefantrine. Lumefantrine was extracted from the sampling paper, then further purified using solid-phase extraction and finally quantified with HPLC. The between-day variation was below 10% over the range 0.4-25 microM. The lower limit of quantification was 0.25 microM in 100 microl capillary blood. No decrease in lumefantrine concentration in dried blood spot is seen after 4 months storage at 22 degrees C. The method was also evaluated in field samples from patients in Tanzania after treatment with lumefantrine/artemether. Lumefantrine could be estimated accurately enough to assess bioavailability and treatment compliance on day 7 (i.e. 4 days after the last dose) after a standard regimen with the lumefantrine/artemether combination. PMID- 17719736 TI - Validated stability-indicating methods for determination of cilostazol in the presence of its degradation products according to the ICH guidelines. AB - Sensitive and selective stability-indicating assay methods (SIAMs) are suggested for the determination of cilostazol (CIL) in the presence of its acid, alkaline and oxidative degradation products. Developing SIAMs is necessary to carry out any stability study. Stress testing of CIL was performed according to the International Conference on Harmonization (ICH) guidelines in order to validate the stability-indicating power of the analytical procedures. Stress testing showed that CIL underwent acid, alkaline and oxidative degradation; on the other hand, it showed stability towards photo- and thermal degradation. Two chromatographic SIAMs were developed, namely HPLC and HPTLC methods. The concentration range and the mean percentage recovery were 1.0-31.0 microg/ml and 99.96+/-0.46 and 0.6-14.0 microg/spot and 99.88+/-1.10 for HPLC and HPTLC methods, respectively. In addition, derivative spectrophotometric methods were developed in order to determine CIL in the presence of its acid degradation product; these were performed by using the third derivative spectra (3D) and the first derivative of the ratio spectra (1DD) methods. The linearity range and the mean percentage recovery were 2.0-34.0 microg/ml and 100.27+/-1.20 for the (3D) method, while they were 2.0-30.0 microg/ml and 99.94+/-1.18 for the (1DD) method. Also, two chemometric-assisted spectrophotometric methods, based on using partial least squares (PLS) and concentration residual augmented classical least squares method (CRACLS), for the determination of CIL were developed. Both methods were applied on zero order spectra of the mixtures of CIL and its acid degradation product, the mean percentage recovery was 100.03+/-1.09 and 99.91+/-1.27 for PLS and CRACLS, respectively. All methods were validated according to the International Conference on Harmonization (ICH) guidelines and applied on bulk powder and pharmaceutical formulations. PMID- 17719737 TI - [Trali: a clinical diagnosis]. PMID- 17719738 TI - Constitutive expression and inducibility of CYP1A1 in the H9c2 rat cardiomyoblast cells. AB - Cardiomyocytes are a valuable tool for studying the drug metabolizing enzymes in the heart. However, isolated cardiomyocytes are rather fragile and difficult to isolate. Therefore, there is an urgent need for an in vitro cell line model. The H9c2 cells are commonly used as an in vitro model for studying the cellular mechanisms and signaling pathways involved in drug-induced cardiotoxicity. These cells maintain many molecular markers of cardiomyocytes and show morphological characteristics of immature embryonic cardiomyocytes. Therefore, in the present study we examined the expression and inducibility of CYP1A1 in the H9c2 rat cardiomyoblast cells. Our results showed that treatment of H9c2 cells with the CYP1A1 inducer, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) significantly induced CYP1A1 at mRNA, protein, and activity levels in a concentration-dependent manner. The RNA synthesis inhibitor, actinomycin D, completely blocked the CYP1A1 mRNA induction by TCDD, indicating the requirement of de novo RNA synthesis through transcriptional activation. In conclusion, we demonstrated for the first time the constitutive expression and inducibility of CYP1A1 in H9c2 cells. Therefore, this cell line offers a unique in vitro model to study the role of CYP1A1 in the pathogenesis of various cardiovascular diseases. PMID- 17719739 TI - An in vitro embryotoxicity assay based on the disturbance of the differentiation of murine embryonic stem cells into endothelial cells. II. Testing of compounds. AB - The embryonic stem cell test (EST) developed by Spielmann et al. [Spielmann, H., Pohl, I., Doering, B., Liebsch, M., Moldenhauer, F., 1997. The embryonic stem cell test, an in vitro embryotoxicity test using two permanent mouse cell lines: 3T3 fibroblasts and embryonic stem cells. In Vitro. Toxicol. 10, 119-127] is currently the most promising in vitro assay to predict the embryotoxic potential of compounds. In this assay the disturbance of the differentiation of embryonic stem (ES) cells into contracting cardiomyocytes by test compounds as well as the direct cytotoxicity of the test compounds on ES cells and 3T3 fibroblasts is analyzed. On the basis of these results and by applying a biostatistical prediction model (PM) [Genschow, E., Scholz, G., Brown, N., Piersma, A., Brady, M., Clemann, N., Huuskonen, H., Paillard, F., Bremer, S., Becker, K., Spielmann, H., 2000. Development of prediction models for three in vitro embryotoxicity tests in an ECVAM validation study. In Vitr. Mol. Toxicol. 13, 51-66; Genschow, E., Spielmann, H., Scholz, G., Pohl, I., Seiler, A., Clemann, N., Bremer, S., Becker, K., 2004. Validation of the embryonic stem cell test in the international ECVAM validation study on three in vitro embryotoxicity tests. Altern. Lab. Anim. 32, 209-244; Genschow, E., Spielmann, H., Scholz, G., Seiler, A., Brown, N., Piersma, A., Brady, M., Clemann, N., Huuskonen, H., Paillard, F., Bremer, S., Becker, K., 2002. The ECVAM international validation study on in vitro embryotoxicity tests: results of the definitive phase and evaluation of prediction models. European Centre for the Validation of Alternative Methods. Altern. Lab. Anim. 30, 151-176] test compounds can be classified as non embryotoxic, weakly or strongly embryotoxic. In order to introduce a further endpoint into the EST, the disturbance of vasculogenesis and/or angiogenesis, a protocol to differentiate ES cells into endothelial cells, was established in the accompanying paper. PECAM-1 and VE-Cadherin gene expressions, quantified by real time TaqMan PCR, were shown to be appropriate molecular markers for the differentiation of ES cells into endothelial cells. In the present study, the disturbance of the differentiation of ES cells into endothelial cells (i.e. the reduction in the expression of PECAM-1 and VE-Cadherin) by six test compounds with known embryotoxic potential was investigated: all-trans-retinoic acid (RA) and 5-fluorouracil (5-FU) are strongly embryotoxic, diphenylhydantoin (DPH) and valproic acid (Val) are weakly embryotoxic and saccharin (Sacch) and penicillin G (Pen G) are non-embryotoxic. In a first step the concentration of the test compound resulting in a 50% inhibition of PECAM-1 and VE-Cadherin gene expression and the concentration leading to a 50% decrease in the viability of ES cells and 3T3 fibroblasts were determined. In a second step and in a first attempt to assess the predictive potential of the newly developed test system the concentration values obtained were applied in the PM of the established EST to classify the selected test compounds. All six test compounds were correctly classified (i.e. the data obtained in vitro correlated with their known embryotoxic potential in vivo). Taken together it can be concluded that the disturbance of the differentiation of murine ES cells into endothelial cells represents a very promising new endpoint in a broadened EST with PECAM-1 and VE Cadherin as specific differentiation marker genes. PMID- 17719741 TI - Comment on Cogniform disorder and cogniform condition: proposed diagnoses for excessive cognitive symptoms. PMID- 17719740 TI - Antigenotoxic role of Centella asiatica L. extract against cyproterone acetate induced genotoxic damage in cultured human lymphocytes. AB - The majority of the Indian population use traditional natural preparations derived from plant material for the treatment of various diseases, and for that reason it becomes necessary to assess the mutagenic potential or modulating action of plants extract when associated with other substances. The genotoxicity testing provides human a risk assessment. Earlier in vitro and in vivo studies reveal that the plant extracts from various parts of the plant play a modulating role in xenobiotic effects. Identification and characterization of some active principles may lead to the development of the strategies to reduce the risk for developing cancer in humans. Cyproterone acetate (CPA), a synthetic progestin is not only a genotoxic agent but also a tumor initiating agent. It is used in oral contraceptives formulations and also in the treatment of various sexual and metabolic disorders. In this context, the antigenotoxic effect of Centella asiatica L. extract was studied against the genotoxic effect induced by CPA on human lymphocytes using chromosomal aberrations and sister chromatid exchanges as parameters. The treatment of the two doses of CPA, i.e. 20 and 30 microM was given along with the C. asiatica extract at the dosages of 1.075 x 10(-4), 2.125 x 10(-4), 3.15 x 10(-4) and 4.17 x 0(-4)g/ml of culture medium. A clear dose dependent decrease in the genotoxic damage of CPA was observed, suggesting a protective role of C. asiatica extract during CPA therapy. The results of the present study suggest that the plant extract per se do not have genotoxic potential, but can modulate the genotoxicity of CPA on human lymphocytes in vitro. PMID- 17719742 TI - Identification, evolution, and association study of a novel promoter and first exon of the human NOD2 (CARD15) gene. AB - Mutations in the NOD2 (CARD15) gene predispose to Crohn's disease (CD), a human chronic inflammatory bowel disorder, and can cause Blau syndrome. During an investigation of an apparent correlation between a frameshifting mutation in the canonical first exon of NOD2 of marmoset and tamarin species and their susceptibility to chronic colitis, we found that, contrary to previous reports, the basal levels of NOD2 transcripts in tissues relevant to CD arise from a distinct novel promoter and first exon. The canonical first exon, by contrast, seems to be of negligible transcriptional importance under physiological conditions, and its reading frame has been disrupted twice during primate evolution. Thus the main NOD2/CARD15 protein isoform produced in humans and other primates is 27 amino acids shorter than previously reported, starting at a conserved methionine in exon 2. We show that there is no significant association between variants in the novel NOD2 promoter region and CD. PMID- 17719743 TI - Sequence variability and protein domain architectures for bovine Toll-like receptors 1, 5, and 10. AB - The mammalian Toll-like receptors (TLRs) play an important role in the recognition of invading pathogens and the modulation of innate immune responses. The primary objective of this study was to characterize single nucleotide polymorphisms (SNPs) and insertion-deletion polymorphisms (indels) within bovine TLRs 1, 5, and 10, thereby facilitating future TLR signaling and association studies relevant to bovine innate immunity. Comparative sequence analysis for 10 bovine breeds derived from Bos taurus and Bos indicus revealed 98 polymorphisms (92 SNPs and 6 indels), with at least 14 nonsynonymous SNPs located within predicted TLR domains considered to be of functional significance. Of the 98 polymorphisms detected, 94 are reported here for the first time. Notably, 2 nonsynonymous SNPs were determined to modulate the prediction of a novel leucine rich repeat (LRR) domain within B. indicusTLR5. Prediction and comparison of TLR protein domain architectures for multiple species revealed seven conserved regions of LRR patterning associated with the three genes investigated. PMID- 17719744 TI - Identification and in silico analysis of functional SNPs of the BRCA1 gene. AB - Single-nucleotide polymorphisms (SNPs) play a major role in the understanding of the genetic basis of many complex human diseases. Also, the genetics of human phenotype variation could be understood by knowing the functions of these SNPs. It is still a major challenge to identify the functional SNPs in a disease related gene. In this work, we have analyzed the genetic variation that can alter the expression and the function of the BRCA1 gene using computational methods. Of the total 477 SNPs, 65 were found to be nonsynonymous (ns) SNPs. Among the 14 SNPs in the untranslated region, 4 were found in the 5' and 10 were found in the 3' untranslated region (UTR). It was found that 16.9% of the nsSNPs were damaging, by both the SIFT and the PolyPhen servers. The UTR Resource tool suggested that 2 of 4 SNPs in the 5' UTR and 3 of 10 SNPs in the 3' UTR might change the protein expression levels. We identified major mutations from proline to serine at positions 1776 and 1812 of the native protein of the BRCA1 gene. From a comparison of the stabilizing residues of the native and mutant proteins, we propose that an nsSNP (rs1800751) could be an important candidate for the breast cancer caused by the BRCA1 gene. PMID- 17719745 TI - fMRI study of language activation in schizophrenia, schizoaffective disorder and in individuals genetically at high risk. AB - BACKGROUND: Structural and functional abnormalities have been found in language related brain regions in patients with schizophrenia. We previously reported findings pointing to differences in word processing between people with schizophrenia and individuals who are at high-risk for schizophrenia using a voxel-based (whole brain) fMRI approach. We now extend this finding to specifically examine functional activity in three language related cortical regions using a larger cohort of individuals. METHOD: A visual lexical discrimination task was performed by 36 controls, 21 subjects at high genetic risk for schizophrenia, and 20 patients with schizophrenia during blood oxygenation level dependent (BOLD) fMRI scanning. Activation in bilateral inferior frontal gyri (Brodmann's area 44-45), bilateral inferior parietal lobe (Brodmann's area 39-40), and bilateral superior temporal gyri (Brodmann's area 22) was investigated. For all subjects, two-tailed Pearson correlations were calculated between the computed laterality index and a series of cognitive test scores determining language functioning. RESULTS: Regional activation in Brodmann's area 44-45 was left lateralized in normal controls, while high-risk subjects and patients with schizophrenia or schizoaffective disorder showed more bilateral activation. No significant differences among the three diagnostic groups in the other two regions of interest (Brodmann's area 22 or areas 39-40) were found. Furthermore, the apparent reasons for loss of leftward language lateralization differed between groups. In high-risk subjects, the loss of lateralization was based on reduced left hemisphere activation, while in the patient group, it was due to increased right side activation. Language ability related cognitive scores were positively correlations with the laterality indices obtained from Brodmann's areas 44-45 in the high-risk group, and with the laterality indices from Brodmann's areas 22 and 44-45 in the patient group. CONCLUSIONS: This study reinforces previous language related imaging studies in high-risk subjects and patients with schizophrenia suggesting that reduced functional lateralization in language related frontal cortex may be a vulnerability marker for schizophrenia. Future studies will determine whether it is predictive of who develops illness. PMID- 17719746 TI - Determinants of help-seeking and system related components of delay in the treatment of first-episode psychosis. AB - INTRODUCTION: Knowledge about factors that influence different components of duration of untreated psychosis (DUP) is important for designing interventions to reduce DUP. METHOD: We tested associations between help-seeking and referral components of DUP (DUP-H and DUP-R, respectively) and the following predictor variables: age, gender, ethnicity, living arrangement, pre-morbid adjustment, age at onset of psychosis, diagnosis, level of symptoms, type of first and total number of mental health contacts prior to and after the onset of psychosis in a sample of 98 first-episode psychosis patients (FEP). RESULTS: Longer DUP-HS was significantly associated with earlier age at onset, diagnosis of schizophrenia spectrum psychosis and poor pre-morbid adjustment during adolescence. Longer DUP R was associated with earlier age at onset and first help-seeking contact having been made with a non-medical professional. CONCLUSIONS: Relatively non-malleable patient characteristics are likely to influence delay in help-seeking while more malleable systemic characteristics influence delay associated with referral for specialized treatment. PMID- 17719747 TI - A spectrum of mutations in keratins K6a, K16 and K17 causing pachyonychia congenita. AB - BACKGROUND: Pachyonychia congenita (PC) is a rare autosomal dominant keratin disorder, subdivided into two major variants, PC-1 and PC-2. Predominant characteristics include hypertrophic nail dystrophy, focal palmoplantar keratoderma and oral leukokeratosis. Multiple steatocystomas that develop during puberty are a useful feature distinguishing PC-2 from PC-1. At the molecular level it has been shown that mutations in keratin K6a or K16 cause PC-1 whereas those in K6b or K17 lead to PC-2. OBJECTIVE: To identify mutations in 22 families presenting with clinical symptoms of either PC-1/focal non-epidermolytic palmoplantar keratoderma (FNEPPK) or PC-2. METHODS: Mutation analysis was performed on genomic DNA from PC patients by direct sequencing. RESULTS: Here, we report four new missense and five known mutations in K6a; one new deletion and three previously identified missense mutations in K16; plus one known mutation in K17. CONCLUSION: With one exception, all these heterozygous mutations are within the highly conserved helix boundary motif regions at either end of the keratin rod domain. In one sporadic case, a unique mutation in K16 resulting in deletion of 24bp was found within the central rod domain, in a child with a phenotype predominantly consisting of focal plantar keratoderma. The identification of mutations in cases of PC is prerequisite for future development of gene-specific and/or mutation-specific therapies. PMID- 17719748 TI - The current status and future direction of percutaneous peptide immunization against melanoma. AB - Dendritic cell (DC)-based tumor immunotherapy is widely known to elicit protective anti-tumor immune responses, although the safety and effectiveness have yet to be thoroughly explored. We reported that a disruption in the stratum corneum barrier resulted in enhanced permeability and alterations in the skin immune system in such a way that epidermal Langerhans cells (LCs) functioned as vigorous antigen presenters for T helper (Th) cells and cytotoxic T lymphocytes (CTLs). In both human and murine models, topical application of melanoma associated antigen peptides onto stratum corneum barrier-disrupted skin, specifically induced tumoricidal immune responses in vivo and in vitro accompanying an increased expression of MHC and co-stimulatory molecules on LCs. In addition, for reasons of simplicity, safety and effectiveness, percutaneous peptide application has demonstrated a certain degree of feasibility in clinical approach in patients with melanoma. In the future, resolution of some of the outstanding issues concerning the selection of the most effective adjuvants in combination with barrier disruption and depletion of regulatory T (Treg) cell mediated immune suppression would appear as essential to improve percutaneous melanoma immunotherapy. PMID- 17719749 TI - Activity of staphylococcal bacteriocins against Staphylococcus aureus and Streptococcus agalactiae involved in bovine mastitis. AB - The inhibitory activity of seven bacteriocins produced by Staphylococcus aureus (aureocins A70, A53, and 215FN) and Staphylococcus epidermidis (Pep5, epidermin, epilancin K7 and epicidin 280) was tested against strains of both S. aureus (165 strains) and Streptococcus agalactiae (74 strains) isolated from udders of cows suffering from bovine mastitis. Most strains of the two species were inhibited by epidermin (>85%), aureocin A53 (>67%) and by a combination of aureocins A70 and A53 (>91%), co-expressed in the genetic background of strain A70, the native producer of aureocin A70. Synergy between aureocins A70 and A53 was also demonstrated, which broadened the spectrum of strains inhibited. The remaining staphylococcins inhibited either none of, or a lower percentage (<48%) of, the mastitis-causing pathogens tested. Our results therefore show that the use of epidermin and/or a combination of aureocins A53 and A70 may represent a new non antibiotic alternative for successfully inhibiting both mastitic staphylococci and streptococci. PMID- 17719750 TI - Digitized fluorescent RFLP analysis (fRFLP) as a universal method for comparing genomes of culturable dsDNA viruses: application to bacteriophages. AB - Identification and classification of bacteriophages remains a cumbersome process even with the use of genotypic approaches, due to the lack of genes present in all phages. Restriction fragment length polymorphism analysis (RFLP) of the viral genome is a universal approach, but RFLP fingerprints obtained on agarose gels remain difficult to compare between laboratories. Here we describe the digitization of RFLP of viral genomes by amplification of all restriction fragments - after ligation of adapters - using primers complementary to the adapters only. Since one of the primers is fluorescently labelled, the restriction fragments become visible to a fluorescent capillary electrophoresis system (ABI310) and their lengths can be digitized immediately. The digitized fluorescent RFLP (fRFLP) fingerprint can be stored as an entry in a library. Dendrogram construction of the fRFLP fingerprints obtained for a total of 69 Caudovirales (tailed bacteriophages) showed that genomically and/or serologically closely related phages clustered, whereas host range was not completely in correspondence with genotype. fRFLP might be a tool for quickly establishing the relationship of newly isolated phages to previously isolated ones and for constructing an fRFLP library electronically accessible on the internet, to which fRFLP patterns of new phages can be compared. PMID- 17719751 TI - Chloramphenicol- and tetracycline-resistant uropathogenic Escherichia coli (UPEC) exhibit reduced virulence potential. AB - It is well documented that uropathogenic Escherichia coli (UPEC) isolates resistant to nalidixic acid have reduced virulence potential. Our goal was to assess whether UPEC isolates resistant to chloramphenicol, tetracycline and streptomycin also exhibit reduced virulence potential. Among 110 human UPEC isolates, the prevalences of the virulence factors fimH, papC, papGII, papGIII, sfa/focDE, afa, hlyA, cnf1, usp, ibeA, fyuA, iroN, iucD, ireA, and K1 and K5 capsules as well as of pathotypes, phylogenetic groups, O antigens and a pathogenicity island (PAI) marker were compared between chloramphenicol-, tetracycline-, streptomycin- and, as a control, nalidixic acid-resistant and susceptible strains. Our findings show that among human UPEC isolates, not only nalidixic acid-resistant but also chloramphenicol- and tetracycline-resistant isolates have reduced virulence potential compared with susceptible strains. To our knowledge, this is the first report of a statistically significant reduction in virulence traits among chloramphenicol- and tetracycline-resistant isolates. PMID- 17719752 TI - A meta-analysis of clinical trials comparing reboxetine, a norepinephrine reuptake inhibitor, with selective serotonin reuptake inhibitors for the treatment of major depressive disorder. AB - The goal of the present work was to conduct a meta-analysis comparing reboxetine and the selective serotonin reuptake inhibitors (SSRIs) for major depressive disorder (MDD). Medline/Pubmed was searched for double-blind, randomized trials comparing these two agents for MDD. The makers of reboxetine (Pfizer Inc.) were also contacted to provide missing data and/or unpublished studies. 9 trials (n=2641) were combined using a random effects model. Response rates were comparable between the SSRI (63.9%) and reboxetine (59.2%)-treated groups (p=0.118). There was no significant difference in the degree of improvement in psychosocial functioning, as measured by the social adaptation self-evaluation scale, between the two groups. Overall discontinuation rates (25.1% versus 32.0%; p=0.015), and the rate of discontinuation due to intolerance (8.5% versus 12.6%; p=0.007) favored SSRI treatment. The rate of discontinuation due to lack of efficacy did not differ significantly between the two groups. SSRI-treated patients were more likely to experience nausea, hypersomnia, and fatigue. Reboxetine-treated patients were more likely to experience constipation, difficulty urinating, and insomnia. These results suggest that the NRI reboxetine and the SSRIs differ with respect to their side-effect profile and overall tolerability but not their efficacy in treating MDD. PMID- 17719753 TI - Factors affecting the loading efficiency of water-soluble drugs in PLGA microspheres. AB - Poly(lactide-co-glycolide), PLGA, microspheres containing blue dextran as a hydrophilic model drug were prepared by a solvent evaporation method from w/o/w emulsions using a micro homogenizer. Effects of surfactant concentration in oil phase, stirring time period and stirring rate in the preparation procedure of primary emulsion (w/o) upon drug-loading efficiency were evaluated. Stirring rate during preparation of primary emulsion and surfactant concentration in oil phase affected drug-loading efficiency and the particle size of primary emulsion. Microspheres having the higher drug-loading efficiency were obtained when size differences between the primary emulsions and the secondary ones were large. That is, when the diameter of the primary emulsion is much smaller than that of the secondary emulsion, PLGA microspheres with high-loading efficiency of blue dextran were obtained. PMID- 17719754 TI - Purification and thermal analysis of perfluoro-n-alkanoic acids. AB - Purification of perfluoro-n-alkanoic acids (C(n)F(2n+1)COOH, n=7, 9, 11, 13, 15 and 17) was made by repeated recrystallizations from n-hexane/acetone mixed solvent, and their purity was found to be more than 99.5% by GC-MS, NMR, and elemental analysis. The thermal behaviors such as melting point and enthalpy change of fusion were investigated using differential scanning calorimetry (DSC). The melting point monotonously increased with increasing carbon number (n) of the acids, while the enthalpy change showed irregularity at n=14. The crystal structure of these acids was found to be dependent upon solvent used for recrystallization; that is, the acids recrystallized from the above solvent becomes more stable energetically, indicating their higher enthalpy change of fusion than that of the solidified acids from fused ones. The solid state was also found to vary depending upon the thermal history, indicating that a few crystal structures of the solid state are quite similar energetically. The melting points (T(m)) of perfluoro-n-alkanoic acids are higher than those of corresponding n-alkanoic acids, and the difference in T(m) increases with increasing carbon number in the acids. PMID- 17719756 TI - Is there a role for radiotherapy in operable rectal cancer? AB - Most patients presenting with rectal cancer will have "operable" disease. The main aim in treating these patients is to achieve complete surgical resection while minimising the rate of local recurrence. The use of radiotherapy has been shown to decrease local recurrence rates and the evidence suggests that this should be used preoperatively. Here we summarise the important trials both before and after the introduction of mesorectal excision. We highlight some of the important issues, including treatment-related toxicity and patient selection for preoperative treatment. PMID- 17719757 TI - Urinary metabolic fingerprinting for amiodarone-induced phospholipidosis in rats using FT-ICR MS. AB - In the research and development for new therapeutic compounds, there has been a focus on detecting the changes of metabolites induced by drug administration and finding surrogate markers to assess its toxicity. We examined the suitability of urinary metabolic fingerprinting using Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) for toxicological assessment in the amiodarone (AMD)-induced phospholipidosis (PLD) rat model. There were more than 400 different ion peaks detected in the negative ion mode analysis with FT-ICR MS. About 20% of the detected ions were altered more than 1.5 fold by AMD-treatment. On the scores plot of principal component analysis (PCA), the ion profiles of the treated were separated time-dependently. The loading plot revealed that the metabolites causing PCA results were m/z 178.05101, 191.01979, 192.06676, 212.00239, 258.9944 and 283.0820. The ion at m/z 178.05101 is considered to be hippurate (HA), 192.06676 is phenylacetylglycine (PAG) and 212.00239 is indican (IDN). These results indicate that PAG, IDN and HA are biomarkers for AMD-induced PLD in urinary metabolic fingerprinting using FT-ICR MS. These markers may be useful for evaluation of chemicals, which have the potential to induce PLD. PMID- 17719758 TI - Haematopoietic cell apoptosis. PMID- 17719759 TI - Immunogenetics: alternative strategies in adaptive immunity and the rise of comparative immunogenomics. PMID- 17719761 TI - Histological and ultrastructural features of gastrointestinal basidiobolomycosis. AB - Basidiobolus ranarum is a fungus found in the dung of amphibians, reptiles, and insectivorous bats. Its structural elements include both hyphae and zygospores. Patients with B. ranarum infection may present with subcutaneous, gastrointestinal, or systemic lesions. Here we report a case of gastrointesinal badidiomycosis in a 13-year-old male child who presented with acute abdomen. Exploration revealed a mass in the ascending colon. On histology, transmural granulomatous inflammation composed of abundant eosinophils, lymphocytes, histiocytes and giant cells was seen. Histochemical stains revealed broad, non septate, hyphae-like structures surrounded by an eosinophilic sheath. On an ultrastructural level, fungal hyphae, spores, and macrophage-laden crystalloids were observed. The diagnosis of gastrointestinal basidiobolomycosis was established and the patient received antifungal treatment. This paper reviews the relevant literature regarding basidiomycosis, and discusses its diverse clinicopathological features, as well as distinguishing it from other diseases. PMID- 17719762 TI - Mating studies, new species, and new reports of Marasmius from northern Thailand. AB - The mating systems operating in seven species of Marasmius collected recently in northern Thailand were determined. Marasmius cremeus belonging to sect. Sicci subsect. Siccini ser. Leonini, and Marasmius straminiceps belonging to sect. Marasmius subsect. Sicciformes are described as new species. Five members of sect. Marasmius were tetrapolar (bifactorial), viz. M. apatelius, M. guyanensis, M. nigrobrunneus, M. ruforotula, and M. straminiceps. Two members of sect. Sicci were bipolar (unifactorial), viz., M. corneri (syn. M. incarnatus) and M. cremeus. Our data support the hypothesis that the mating system is consistent within infrageneric taxa. The seven species that are herein described, illustrated, and compared with phenetically similar species represent the first reports for this genus in Thailand. PMID- 17719760 TI - Histone deacetylase inhibitors and transplantation. AB - Simply detecting the presence or absence of Foxp3, a transcription factor characteristic of naturally occurring CD4+ CD25+ regulatory T cells (Tregs), now appears of minimal value in predicting the outcome of immunologic responses, since dividing human CD4+ effector T cells can induce Foxp3 without attaining repressive functions, and additional molecular interactions, as well epigenetic events, affect Foxp3-dependent Treg functions in humans and mice. Experimentally, in vivo and in vitro studies show histone deacetylase inhibitors (HDACi) can enhance the numbers and suppressive function of regulatory T cells (Tregs) by promoting Foxp3+ cell production, enhancing chromatin remodeling within Tregs, and inducing acetylation of Foxp3 protein itself. Human studies consistent with a role for HDACi in controlling Fox3-dependent Treg functions are also available. We review these molecular interactions and how they may be exploited therapeutically to enhance Treg-dependent functions, including post transplantation. PMID- 17719763 TI - Tiotropium administered by a pressurized metered dose inhaler (pMDI) and spacer produces a similar bronchodilator response as that administered by a Rotahaler in adult subjects with stable moderate-to-severe COPD. AB - BACKGROUND: Tiotropium is a new long-acting anticholinergic bronchodilator, which is recommended as first-line therapy in the management of chronic obstructive pulmonary disease (COPD). It is currently available in the form of a dry powder inhaler worldwide. Some COPD patients find it difficult to generate inspiratory flow rates of up to 40 l/min, which is required for the drug to reach the airways. To overcome this, a new pMDI form has been developed for administration of tiotropium in patients with COPD. The clinical efficacy of this mode of tiotropium delivery has, so far, not been compared with the currently available dry powder inhaler (DPI) devices. AIMS AND OBJECTIVES: To compare the bronchodilator effects of a single dose of 18 mcg of tiotropium administered via a pressurized meter dose inhaler (pMDI) and spacer with the currently available DPI form through Rotahaler. STUDY DESIGN: A randomized, double-blind, double dummy, three-period, placebo-controlled, crossover, single-center study was conducted in 19 patients with stable COPD. Single doses of tiotropium (18 mcg) or placebo were administered on three separate study days (4-7 days apart) through a Rotahaler and pMDI with a non-static spacer (Zerostat, Cipla Ltd.). During each study visit forced expiratory volume in 1s (FEV(1)) and forced vital capacity (FVC) were measured over a period of 24 h at 11 different time points (0, 15, 30 min, 1, 2, 3, 4, 6, 8, 12 and 24h), using a bellows spirometer (Vitalograph) 2160, UK) while static parameters like inspiratory capacity (IC), residual volume (RV), intrathoracic gas volume (ITGV) and total lung capacity (TLC) were measured by bodyplethysmography (Jaeger Masterscreen, Germany) at 0 min, 3, 8 and 24 h. RESULTS: Tiotropium administered through both pMDI (and spacer) and DPI showed significantly better mean FEV(1) and mean FVC differences from baseline, in terms of mean maximum change and area under curve over a period of 24 h (AUC(0-24 h)), as compared to placebo. The mean IC and trough FEV(1) values also improved significantly with tiotropium administered through both the devices as compared to placebo. For all these parameters, there was no difference in the efficacy between pMDI and DPI. There was also no significant difference between the time to onset, time to maximum response and duration of response between tiotropium administered through both the study devices. On the other hand, there was no significant difference in RV, ITGV and TLC by a single dose of tiotopium delivered through either of the devices when compared with placebo over a period of 24 h. CONCLUSION: This is the first study to demonstrate that tiotropium administered by pMDI and spacer shows a superior time-dependent bronchodilator response when compared to placebo, and that this therapeutic efficacy is similar to tiotropium administered by DPI. We recommend the use of tiotropium administered through a pMDI and spacer to those COPD patients who prefer to use the pMDI device, and especially in those who cannot generate sufficient inspiratory flows required for dry powder inhaler devices. PMID- 17719765 TI - Benefits of a tiered approach in environmental testing, analysis, modelling and defining regulatory criteria. PMID- 17719764 TI - Pulmonary arterial pulse pressure and mortality in pulmonary arterial hypertension. AB - In the Framingham studies, systemic arterial pulse pressure correlated linearly with morbidity and mortality. Right ventricular (RV) systolic dysfunction and pulmonary circulation stiffening result in abnormalities of pulmonary arterial (PA) pulse pressure in PA hypertension (PAH). We investigated the prognostic potential of PA pulse pressure in 67 patients with PAH diagnosed between January 1996 and March 2004 (33 idiopathic PAH, 34 PAH-connective tissue disease). The population was arbitrarily divided into tertiles of PA pulse pressure (= systolic diastolic PA pressure) and 5-year mortality was assessed using the Kaplan-Meier method. The extent of RV systolic dysfunction and pulmonary circulation stiffening within each tertile was assessed by comparing the mean cardiac index and alpha (a recently described measure of pulmonary circulation distensibility) in each. Independent predictors of mortality were identified by Cox regression. Five-year mortality rates in patients with low, intermediate and high pulse pressures were 40%, 91% and 54%, respectively. Pulse pressure did not independently predict mortality, but cardiac index, 6-min walk test distance and mixed venous oxygen saturation did. Pulse pressure correlated with circulation stiffening (alpha) but did not correlate with cardiac index which tended to be lower in patients with intermediate pulse pressure and high mortality. PA pulse pressure correlated with pulmonary circulation stiffening but did not predict mortality in this study. RV dysfunction provided better prognostic information and probably explains the higher mortality seen in patients with intermediate pulse pressure. PMID- 17719766 TI - Amperometric glucose sensor based on catalytic reduction of dissolved oxygen at soluble carbon nanofiber. AB - This work shows excellent catalytic activity of soluble carbon nanofiber (CNF), which was obtained with a simple nitric acid treatment, toward the electroreduction of dissolved oxygen at a low operating potential. Thus the CNF was applied in the construction of amperometric biosensors for oxidase substrates using glucose oxidase as a model. The good dispersion of CNF led to convenient preparation and acceptable repeatability of the proposed sensors. UV-vis spectra, Fourier transform infrared spectra, X-ray photoelectron spectra and titration curves demonstrated that the good dispersion resulted from the large numbers of surface oxygen-rich groups produced in the treatment process. The membrane of CNF showed good stability and provided fast response to dissolved oxygen with a linear range from 0.1 to 78 microM and detection limit of 0.07 microM. The proposed glucose biosensor could monitor glucose ranging from 10 to 350 microM with detection limit of 2.5 microM and sensitivity of 36.3 nA cm(-2) microM(-1). The coefficients of variation for intra-assay were 4.7 and 3.2% at glucose concentrations of 20 and 210 microM, respectively. The use of a low operating potential (-0.3 V) and Nafion membrane produced good selectivity toward the glucose detection. CNF-based biosensors would provide wide range of bioelectrochemical applications in different fields. PMID- 17719767 TI - Microbial regulatory and metabolic networks. AB - Reconstruction of transcriptional regulatory and metabolic networks is the foundation of large-scale microbial systems and synthetic biology. An enormous amount of information including the annotated genomic sequences and the genomic locations of DNA-binding regulatory proteins can be used to define metabolic and regulatory networks in cells. In particular, advances in experimental methods to map regulatory networks in microbial cells have allowed reliable data-driven reconstruction of these networks. Recent work on metabolic engineering and experimental evolution of microbes highlights the key role of global regulatory networks in controlling specific metabolic processes and the need to consider the integrated function of multiple types of networks for both scientific and engineering purposes. PMID- 17719769 TI - The anthracycline-trastuzumab interaction: Up-regulated binding may provide vital mechanistic insight. PMID- 17719768 TI - 111Indium-trastuzumab visualises myocardial human epidermal growth factor receptor 2 expression shortly after anthracycline treatment but not during heart failure: a clue to uncover the mechanisms of trastuzumab-related cardiotoxicity. AB - AIM: Trastuzumab can induce cardiotoxicity, particularly when combined with anthracyclines. Myocardial human epidermal growth factor receptor 2 (HER2) expression may be transiently upregulated by a compensatory mechanism following cardiac stress. 111In-DTPA-trastuzumab, scintigraphy can detect HER2 positive tumour lesions, however previously, we found myocardial uptake in only 1 of the 15 anthracycline-pre-treated patients with a median of 11 months after the last anthracycline administration. To evaluate whether myocardial HER2 expression is upregulated by anthracycline-induced cardiac stress or in case of heart failure by chronic pressure or volume overload, we performed 111In-DTPA-trastuzumab scans in patients shortly after anthracyclines and with non-anthracycline-related heart failure. METHODS: Patients within 3 weeks after undergoing 4-6 cycles first-line anthracycline-based chemotherapy and patients with heart failure due to cardiac disease underwent gammacamera imaging 48 and 96 h after 111In-DTPA-trastuzumab intravenously. RESULTS: Myocardial 111In-DTPA-trastuzumab uptake was observed in 5 out of 10 anthracycline-treated patients, who all were without symptomatic cardiac dysfunction. None of the 10 heart failure patients showed myocardial uptake. CONCLUSION: Shortly after completion of anthracycline treatment, myocardial HER2 over-expression was detectable in 50% of the patients. 111In-DTPA trastuzumab scintigraphy after anthracyclines prior to adjuvant trastuzumab potentially identifies patients susceptible for trastuzumab-related cardiotoxicity and thus may facilitate the optimal timing of trastuzumab therapy. PMID- 17719771 TI - Pediatric germ cell tumors. AB - Pediatric germ cell tumors are a diverse group of neoplasms with variable clinical behaviors, depending upon the age and site of presentation. Most result from sporadic mutations, although environmental exposures and other genetic aberrations may play a role. Platinum-based chemotherapy has dramatically improved the event-free and overall survival outcomes of pediatric patients with malignant germ cell tumors over the past two decades. Prognosis is dependent on tumor stage and location. Patients with gonadal germ cell tumors have at least a 95% 5-year survival for early stage disease and at least a 85% 5-year survival for advanced stages. In general, extragonadal germ cell tumors carry a poorer prognosis with mediastinal location having the worst outcomes (70% 4-year survival). Current trials are focused on maintaining similar excellent outcomes while reducing morbidity by reducing the dose and duration of chemotherapy. Cytogenetic research studies have found chromosomal aberrations specific to some of these tumors that may serve as prognosticators and even direct therapy. PMID- 17719770 TI - Endogenous estrogen, testosterone and progesterone levels in relation to breast cancer risk. AB - Multiple lines of evidence support a central role of hormones in the etiology of breast cancer. In epidemiologic studies, considerable effort has focused on delineating the role of endogenous hormones in risk of breast cancer among postmenopausal women. Recently, substantial additional data has accrued from prospective studies where endogenous hormones are measured in study subjects prior to disease diagnosis. In this review, the epidemiologic evidence linking sex steroids--estrogens, testosterone, and progesterone, specifically--with subsequent risk of breast cancer in both premenopausal and postmenopausal women is summarized. Overall, a strong positive association between breast cancer risk and circulating levels of both estrogens and testosterone has now been well confirmed among postmenopausal women; women with hormone levels in the top 20% of the distribution (versus bottom 20%) have a two- to three-fold higher risk of breast cancer. Evidence among premenopausal women is more limited, though increased risk associated with higher levels of testosterone is consistent. However, both positive and null associations have been observed with estrogens and progesterone and clearly more evaluation is needed. PMID- 17719772 TI - Abdominal desmoid tumors. AB - Desmoid tumors are rare, benign, fibromatous lesions that are the result of abnormal proliferation of myofibroblasts. Desmoid tumors can be classified as extra-abdominal and abdominal. Abdominal desmoid tumors are either superficial or intraabdominal. These tumors are associated with a high recurrence rates, even if their microscopic characters indicate a benign disease; their biologic behavior often indicates rather a "malignant" disease, which can cause even the death. Intraabdominal desmoid tumors can engulf surrounding viscera and vessels, thereby greatly complicating their surgical treatment. Management is multidisciplinary. Simple observation is a reasonable management option for asymptomatic patients; spontaneous regression of these tumors may be observed. Complete excision is the treatment of choice for tumors causing symptoms or complications. Surgery should be minimized as much as feasible, while at the same time achieving free margins. Adjuvant therapy should be considered in selected cases; the role of other management options (including gene transfer therapy) is currently under intensive investigation. PMID- 17719773 TI - Conversion of sewage sludge into lipids by Lipomyces starkeyi for biodiesel production. AB - The potential of accumulation of lipids by Lipomyces starkeyi when grown on sewage sludge was assessed. On a synthetic medium, accumulation of lipids strongly depended on the C/N ratio. The highest content of lipids was measured at a C/N-ratio of 150 with 68% lipids of the dry matter while at a C/N-ratio of 60 only 40% were accumulated. Within a pH range from 5.0 to 7.5 the highest lipid accumulation was found at pH 5.0 while the highest yield per litre was pH 6.5. Although sewage sludge had no inhibitory effects on growth or accumulation on L. starkeyi when added to synthetic medium, there was no significant growth on untreated sewage sludge. However, pretreatment of sludge by alkaline or acid hydrolysis, thermal or ultrasonic treatment lead to accumulation of lipids by L. starkeyi with highest values of 1 g L(-1) obtained with ultrasound pre-treatment. Based on the content of free fatty acids and phosphorus, lipids accumulated from sewage sludge could serve as a substrate for the production of biodiesel. PMID- 17719774 TI - Effects of cadmium and arsenic on growth and metal accumulation of Cd hyperaccumulator Solanum nigrum L. AB - Remediation of heavy metal contaminated sites using hyperaccumulators presents a promising alternative to current environmental methodologies. In the pot-culture experiment, the effects of Cd, and Cd-As on the growth and its accumulation in the Cd-hyperaccumulator (Solanum nigrum L.) were determined. No reduction in plant height and shoot dry biomass was noted when the plants were grown at Cd concentration of 1.0. The plant can be classified as a Cd hyperaccumulator. Growing in the presence of 10 mg/kg Cd and 50 mg/kg As, the plant height and shoot dry matter yields did not decrease significantly (p>0.05) compared to that at 10 mg/kg Cd, however the stem Cd content increased by 28%. It was also observed that S. nigrum used exclusion strategy to reduce As uptake in the roots and restricted translocation into the shoots, resulting in As contents of the plant being root>leaf>stem>seed. The Cd accumulation capacity coupled with its relatively high As tolerance ability could make it useful for phytoremediation of sites co-contaminated by Cd and As. PMID- 17719775 TI - Dimensional analysis for modeling oxygen transfer in rotating biological contactor. AB - In rotating biological contactors (RBC), the oxygen mass transfer coefficient (KLa) is often inadequately predicted by the available models. Hence, dimensional analysis based empirical models were developed for predicting KLa and the component of KLa due to turbulence (KLat) using data available in the literature. The overall oxygen transfer number (OTN) and its component due to turbulence (OTNt) were defined as dimensionless groups based on KLa and KLat, respectively. They were expressed as a function of dimensionless groups, formed using disc diameter (D), area of discs (Ad), rotational speed (omega) and cross-sectional area of the tank (At). OTN was also a function of thickness of the water film on the disc (delta) and working volume of the reactor (V). Decrease in number of discs and decrease in (Ad/At) resulted in decreasing OTN but increasing OTNt. Both OTNt and OTN increased with increase in omega. The proposed empirical models will facilitate scale-up of RBCs. PMID- 17719776 TI - Evaluation of the efficacy of upflow anaerobic sludge blanket reactor in removal of colour and reduction of COD in real textile wastewater. AB - The upflow anaerobic sludge blanket (UASB) reactor was evaluated for its efficacy in decolourization and reduction in chemical oxygen demand (COD) of real textile wastewater (RTW) under different operational conditions. The efficiency of UASB reactor in reducing COD was found to be over 90%. Over 92% of colour removal due to biodegradation was achieved. The activities of the anaerobic granules were not affected during the treatment of textile wastewater. Cocci-shaped bacteria were the dominant group over Methanothrix like bacteria in textile wastewater treatment. Alkalinity, volatile fatty acids (VFA) content and pH in effluents indicated that the anaerobic process was not inhibited by textile wastewater. It is concluded that UASB reactor system can effectively be used in the treatment of textile wastewater for the removal of colour and in the reduction of COD. PMID- 17719777 TI - Thermal stability and conformational changes of transglutaminase from a newly isolated Streptomyces hygroscopicus. AB - Thermal stability and conformational changes of transglutaminase (TGase) from a newly isolated Streptomyces hygroscopicus were investigated in this study. The inactivation kinetics of the microbial transglutaminase (MTGase) was fitted using one-step inactivation model. It was much more stable under 40 degrees C. The half lives for the MTGase at 50 degrees C and 60 degrees C were only 20 min and 8 min, respectively. Spectroscopic studies of the enzyme suggested conformational transition from ordered secondary structural elements (alpha/beta-protein) to unordered structure during thermal denaturation. Some polyols could improve the thermal stability of the enzyme. Among the polyols examined, the prolonged half lives of 40 min at 50 degrees C and 20 min at 60 degrees C were gained by adding 10% glycerol. The results of differential scanning calorimetric (DSC) analysis showed a distinct transition peak with a significant greater Tm and DeltaH for the MTGase mixed with polyols in comparison with the control, which indicated that the polyols could maintain the natural structure of the enzyme to some extent. The SDS-PAGE electrophoresis of cross-linked casein confirmed that the stabilizers could protect the MTGase from thermal denaturation. PMID- 17719778 TI - Can compost improve Quercus pubescens Willd establishment in a Mediterranean post fire shrubland? AB - The aim of the study was to evaluate the effects of sewage sludge compost (control, 20 kg m(-2), 40 kg m(-2)) supplied to Quercus pubescens Willd seedlings planted in a post-fire calcareous site in Provence (France). Changes in soil properties, seedling survival, growth and nutrition were monitored 7 months, 1.5 years and 2.5 years after amendment, and possible trace metal contamination of soil and seedlings by compost was also evaluated. Compost improved overall soil fertility by increasing organic matter, cation exchange capacity, total N and exchangeable P, K, Mg and B concentrations, but 40 kg m(-2) induced a more significant and more durable effect than 20 kg m(-2). However, the compost had no effect on seedling survival and growth, but increased foliar P and B concentrations at 40 kg m(-2). No foliar contamination of seedlings by trace metals occurred, although amendment increased exchangeable Cu and Zn concentrations in soil. Compost P and exchangeable Cu and Zn concentrations could induce eutrophication and water pollution, and limit rates that can be applied without environmental hazard. PMID- 17719779 TI - Synthesis and antimicrobial evaluation of new chalcones containing piperazine or 2,5-dichlorothiophene moiety. AB - Two new series of chalcones have been synthesized by reacting 1-(4-piperazin-1-yl phenyl)ethanone and 1-(2,5-dichloro-3-thienyl)-1-ethanone with different substituted benzaldehydes in turn by Claisen-Schmidt condensation. The compounds have been characterized by IR, (1)H NMR spectral and microanalysis data. All the synthesized compounds have been evaluated for antimicrobial activity. Some of these derivatives are potentially active against Gram-positive bacteria, Staphylococcus aureus and Escherichia coli while the most potent compound (1) in this study showed MIC(50) value of 2.22 microg/mL against Candida albicans. PMID- 17719780 TI - False negative histochemical reaction for myophosphorylase activity in fulminant sepsis due to methicillin resistant Staphylococcus aureus. AB - We report a false negative histochemical reaction for myophosphorylase in the case of an 11 year old with fulminant Staphylococcus aureus. Due to increased creatine kinase levels and marked myoglobinuria a muscle biopsy was performed prior to death. The biopsy revealed rhabdomyolysis, glycogen depletion and absent myophosphorylase reactivity. Subsequent myophosphorylase quantification was normal. This unique case of a false negative myophosphorylase histochemical reaction is apparently related to sepsis. PMID- 17719782 TI - Systemic adjuvant therapies and radiotherapy to the conserved breast: strategies revisited. AB - The rapid increase in the use of both radiotherapy and systemic therapy for patients with early breast cancer requires reconsideration of the strategies that have been used in the past for combining both treatments. In these considerations the impact of both radiotherapy as well as systemic therapy on local control and survival of breast cancer have to be considered. An important point for discussion has often been the sequencing of radiotherapy and systemic treatment. Nowadays the possibilities of trastuzumab for her-2 neu positive breast cancer leads to the question whether or not this can be combined with radiotherapy. Finally new possibilities of sophisticated radiotherapy approaches allow further minimizing the late toxicity of radiotherapy. PMID- 17719783 TI - Application of aromatase inhibitors in endocrine responsive breast cancers. AB - Aromatase (estrogen synthetase) inhibitors (AIs) have been incorporated into adjuvant treatment of early-stage breast cancer in post-menopausal women and their role in pre-menopausal is being investigated. Several questions regarding AIs remain unanswered: optimal sequence with tamoxifen; optimal duration and the best agent in the class. The benefits of extending therapy beyond 5 years has been established by the MA17 trial and many follow-on trials are exploring prolonged therapy. Several strategies to overcome de novo and acquired resistance are being explored. Improving on the "total estrogen blockade" by adding fulvestrant is one example; blocking collaborating cell signaling pathways is another. Candidate targets for this include the erbB2, IGF1R and the mTOR cell survival pathway. Identification of both host (pharmacogenomic) and tumor (genomic) signatures as prognostic and predictive factors will help to select patients for appropriate therapies in the future and reduce the number needed to treat to benefit a few. PMID- 17719781 TI - Exploiting the apoptotic actions of oestrogen to reverse antihormonal drug resistance in oestrogen receptor positive breast cancer patients. AB - The ubiquitous application of selective oestrogen receptor modulators (SERMs) and aromatase inhibitors for the treatment and prevention of breast cancer has created a significant advance in patient care. However, the consequence of prolonged treatment with antihormonal therapy is the development of drug resistance. Nevertheless, the systematic description of models of drug resistance to SERMs and aromatase inhibitors has resulted in the discovery of a vulnerability in tumour homeostasis that can be exploited to improve patient care. Drug resistance to antihormones evolves, so that eventually the cells change to create novel signal transduction pathways for enhanced oestrogen (GPR30+OER) sensitivity, a reduction in progesterone receptor production and an increased metastatic potential. Most importantly, antihormone resistant breast cancer cells adapt with an ability to undergo apoptosis with low concentrations of oestrogen. The oestrogen destroys antihormone resistant cells and reactivates sensitivity to prolonged antihormonal therapy. We have initiated a major collaborative program of genomics and proteomics to use our laboratory models to map the mechanism of subcellular survival and apoptosis in breast cancer. The laboratory program is integrated with a clinical program that seeks to determine the minimum dose of oestrogen necessary to create objective responses in patients who have succeeded and failed two consecutive antihormonal therapies. Once our program is complete, the new knowledge will be available to translate to clinical care for the long-term maintenance of patients on antihormone therapy. PMID- 17719784 TI - Branching out: meiotic recombination and its regulation. AB - Homologous recombination is a dynamic process by which DNA sequences and strands are exchanged. In meiosis, the reciprocal DNA recombination events called crossovers are central to the generation of genetic diversity in gametes and are required for homolog segregation in most organisms. Recent studies have shed light on how meiotic crossovers and other recombination products form, how their position and number are regulated and how the DNA molecules undergoing recombination are chosen. These studies indicate that the long-dominant, unifying model of recombination proposed by Szostak et al. applies, with modification, only to a subset of recombination events. Instead, crossover formation and its control involve multiple pathways, with considerable variation among model organisms. These observations force us to 'branch out' in our thinking about meiotic recombination. PMID- 17719785 TI - Focus on mitochondria: introducing a new series in Trends in Cell Biology. PMID- 17719787 TI - Modulation of flexor reflexes by static and dynamic hip proprioceptors in chronic human spinal cord injury. AB - The aim of this study was to investigate the influence of hip proprioceptors on the organisation of the flexor reflex elicited by nociceptive stimulation in individuals with spinal cord injury. The influence of hip position and passive movement were tested in 10 subjects with chronic spinal cord injury. Stimuli were tested isometrically with the hip in three positions. Additionally, the response was also measured to stimuli applied with the hip at midposition during imposed hip flexion and extension movement. The torque and EMG responses were compared in order to identify the postural and movement-dependent modulation of the withdrawal reflex. Ankle and hip torques were significantly modulated by hip position (ANOVA, p<0.05), with the largest torque response obtained in the hip extended position, compared with the flexed position. We also observed a significant difference between the flexor reflex during movement and with the leg isometric. Ankle and hip torque and tibialis anterior electromyograms were significantly higher in the movement conditions than the isometric condition (Tukey test, p<0.05). We postulate that inputs from hip proprioceptors enhance the withdrawal reflex response. Movement appears to increase the response, regardless of movement direction, suggesting a novel role for the dynamic components of hip afferents. PMID- 17719788 TI - Effects of angle and laminectomy on triangulated pedicle screws. AB - We aimed to demonstrate the effect of angle and laminectomy on paired pedicle screws to determine whether a 90 degrees screw angle is optimal as has been previously suggested. According to the angle between right and left screws, 28 calf vertebrae were divided into three groups and instrumented as follows: Group I: 60 degrees screw angle; Group II: 90 degrees angle; Group III: 60 degrees angle with laminectomy. The screws were connected using rods and cross-fixators and tested to peak pullout force. Triangulated pedicle screws provided 76.5% more pullout strength than single screws. Most of the specimens failed through loss of convergence angle (toggling of screws on the rods) and subsequent uni- or bilateral screw pullout. Mean+/-SD peak loads were: Group I: 2071+/-622 N; Group II: 1753+/-497 N; Group III: 2186+/-587 N. The differences were not significant (p>0.05). 90 degrees triangulation was not associated with a superior pullout performance versus conventional 60 degrees triangulation, suggesting that achieving additional triangulation angle is not necessary to obtain increased pullout strength. Laminectomy did not alter the effect of triangulation on fixation strength. PMID- 17719789 TI - Simple measurement of spinal cord evoked potential: a valuable data source in the rat spinal cord injury model. AB - Measurement of spinal cord evoked potentials (SCEPs) is proposed as a means of predicting locomotion outcome in the rat spinal cord injury (SCI) model. Using 55 rats, three reproducible peak waves (waves I, II and III) were observed during stimulation at the C7 level with recording at the L1 epidural space. Hemisection at the T13 level showed three wave loss patterns: wave III loss only, loss of both wave II and III, and loss of all three waves. Defining an ideal SCI model as establishment of stable monoparesis or paraparesis, all animals in the wave II III loss group showed favorable results. Histological data and electrophysiological properties allowed reasonable assumptions of wave origin: wave I from extrapyramidal tracts, wave II from the ventral corticospinal tract, and wave III from the dorsal corticospinal tract. Complete destruction of pyramidal tracts in both dorsal and ventral fibers was essential for long-term impairment of locomotion. PMID- 17719790 TI - Bipolar radiofrequency in the human meniscus. Comparative study between patients younger and older than 40 years of age. AB - PURPOSE: To morphohistologically evaluate the effect of four increasing intensities of bipolar radiofrequency (RF) on the human meniscus and to compare the changes seen in the menisci from patients younger and older than 40 years old. METHODS: Thirty fresh menisci were divided in two groups. Group 1: 12 menisci from patients younger than 40 y.o.; Group 2: 18 menisci from patients older than 40 y.o. Groups 1 and 2 were divided in four zones and subjected in vitro, for 3 s, to four intensities of bipolar RF energy. The samples were studied macroscopically, and microscopically. RESULTS: Thermal changes were present between 0 and 4000 microm from the meniscal surface, with an average of 1699 microm (S.D. 740), and was significantly higher on the ablation than the coagulation group (p<0.001). We found a significant difference between the depth of thermal changes in the menisci from patients younger and older than 40 years old at medium intensities of RF energy (p=0.038 and p=0.044). CONCLUSIONS: Although bipolar RF can cause deep thermal changes (up to 4000 microm) on the human meniscus, this effect depends on the magnitude of the energy applied. When comparing the effect between younger and older patients, the changes were deeper in the older group when RF was applied at medium intensities. CLINICAL RELEVANCE: Based on our findings, we recommend to exert precaution when applying RF energy at medium intensities in the degenerative meniscus, due to a deeper thermal effect in this group. PMID- 17719791 TI - Discovering benzamide derivatives as glycogen phosphorylase inhibitors and their binding site at the enzyme. AB - A series of novel benzamide derivatives was designed, synthesized, and their inhibitory activities against glycogen phosphorylase (GP) in the direction of glycogen synthesis by the release of phosphate from glucose-1-phosphate were evaluated. The structure-activity relationships (SAR) of these compounds are also presented. Within this series of compounds, 4m is the most potent GPa inhibitor (IC(50)=2.68 microM), which is nearly 100 times more potent than the initial compound 1. Analysis of mapping between pharmacophores of different binding sites and each compound demonstrated that these benzamide derivatives bind at the dimer interface of the rabbit muscle enzyme, and possible docking modes of compound 4m were explored by molecular docking simulation. PMID- 17719792 TI - Determination of radioactivity levels and hazards of soil and sediment samples in Firtina Valley (Rize, Turkey). AB - The natural radioactivity levels in soil and sediment samples of Firtina Valley have been determined. To our knowledge, there seems to be no information about radioactivity level in the Firtina Valley soils and sediments so far. For this reason, soil and sediment samples were collected along the Firtina Valley and analysis on the collected samples were carried out to determine 238U, 232Th, 40K and 137Cs radioisotopes using high purity germanium detector. The activity concentrations obtained for 226Ra, 214Pb, 214Bi, 228Ac, 208Tl, 40K and 137Cs are given in the unit of Bq/kg. The results have been compared with other radioactivity measurements in different country's soils and sediments. The radium equivalent activity (Raeq), the absorbed dose rate (D), the external hazard index (Hex), the annual gonadal dose equivalent (AGDE) and the annual effective dose equivalent (AEDE) were also calculated and compared with the international recommended values. PMID- 17719793 TI - Adsorption of ions onto high silica volcanic glass. AB - Chemical fingerprint techniques are frequently applied to airborne volcanic eruption products, so-called tephra, such as ash and pumice for archeological and geoscientific purposes. However, in some cases, a meaningful interpretation of the results is complicated by superficial contaminations. Therefore, this situation was simulated by the use of powdered rhyolitic pumice to investigate its capability to adsorb several ions from aqueous solutions. Using neutron activation analysis, adsorption could be proven for Cr(3+), Cr(2)O(7)(2-) (dichromate), Fe(3+), Co(2+), HAsO(4)(2-) (hydrogen arsenate), Rb(+), Sr(2+), Cs(+), Ba(2+), La(3+), Ce(3+), Ce(4+), Sm(3+), Th(4+) and UO(2)(2+), which is a clear evidence for the interaction of those ions with the volcanic glass. In our experiments, pumice powder showed the ability to adsorb ions in the range from 1.8 mg kg(-1) (in case of HAsO(4)(2-)) to 5.8 wt% (in case of Fe(3+)). Adsorption is probably due to ion-exchange reactions. It could also be shown that a few ions are not adsorbed in detectable quantities: Na(+), K(+), Fe(2+), Zn(2+) and Nd(3+). The knowledge about adsorption of ions enables us not only to examine the possible influence of contaminations where chemical fingerprinting methods are applied to volcanic material for archaeometry, but it also suggests the technical application of pumiceous materials for technical purposes, like water purification or as an adsorbent in the final storage of nuclear waste. In another series of INAA supported experiments, the influence of chemicals like ascorbic acid, acetic acid, HCl, HF, HNO(3), H(2)O, H(2)O(2), H(3)PO(4), H(2)SO(4), NaOH and NH(3) on the bulk composition of pumice powder was investigated-resulting in no detectable change. We conclude that superficially contaminated tephra can be washed in diluted HF to remove contaminations without influencing the chemical fingerprint. PMID- 17719794 TI - DJ-1 (PARK7) is associated with 3R and 4R tau neuronal and glial inclusions in neurodegenerative disorders. AB - Mutations in the DJ-1 gene are associated with autosomal recessive Parkinson's disease (PD), but its role in disease pathogenesis is unknown. This study examines DJ-1 immunoreactivity (DJ-1 IR) in a variety of neurodegenerative disorders, Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) with Pick bodies, FTLD with MAPT mutations, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), in which hyperphosphorylated tau inclusions are the major pathological signature. DJ-1 IR was seen in a subset of neurofibrillary tangles (NFTs), neuropil threads (NTs), and neurites in extracellular plaques in AD; tau inclusions in AD contained both 3R and 4R tau. A subset of Pick bodies in FTLD showed DJ-1 IR. In PSP, DJ-1 IR was present in a few NFTs, NTs and glial cell inclusions. In CBD, DJ-1 IR was seen only in astrocytic plaques. In cases of FTLD with MAPT mutations that were 4R tau positive (i.e. N279K and exon 10+16 mutations), DJ-1 IR was present mostly in oligodendroglial coiled bodies. However, in MAPT R406W mutation cases, DJ-1 IR was associated mainly with NFTs and NTs and these were both 3R and 4R tau positive. No DJ-1 IR was present in FTLD with ubiquitin inclusions (FTLD-U). In AD and FTLD with Pick bodies, DJ-1 protein was enriched in the sarkosyl-insoluble fractions of frozen brain tissue containing insoluble hyperphosphorylated tau, thus strengthening the association of DJ-1 with tau pathology. Additionally using two-dimensional gel electrophoresis, we demonstrated accumulation of acidic pI isoforms of DJ-1 in AD brain, which may compromise its normal function. Our observations confirm previous findings that DJ-1 is present in a subpopulation of glial and neuronal tau inclusions in tau diseases and associated with both 3R and 4R tau isoforms. PMID- 17719795 TI - Gas-phase stability of G-quadruplex DNA determined by electrospray ionization tandem mass spectrometry and molecular dynamics simulations. AB - The relative gas-phase stabilities of seven quadruplex DNA structures, [d(TG(4)T)](4), [d(T(2)G(3)T)](4), [d(G(4)T(4)G(4))](2), [d(T(2)AG(3))(2)](2), d(T(2)AG(3))(4), d(T(2)G(4))(4), and d(G(2)T(4))(4), were investigated using molecular dynamics simulations and electrospray ionization mass spectrometry (ESI MS). MD simulations revealed that the G-quadruplexes maintained their structures in the gas phase although the G-quartets were distorted to some degree and ammonium ions, retained by [d(TG(4)T)](4) and [d(T(2)G(3)T)](4), played a key role in stabilizing the tetrad structure. Energy-variable collisional activated dissociation was used to assess the relative stabilities of each quadruplex based on E(1/2) values, and the resulting order of relative stabilities was found to be [d(TG(4)T)](4) >> d(T(2)AG(3))(4) approximately d(T(2)G(4))(4) > [d(T(2)G(3)T)](4) > [d(T(2)AG(3))(2)](2) approximately d(G(2)T(4))(4) approximately [d(G(4)T(4)G(4))](2.) The stabilities from the E(1/2) values generally paralleled the RMSD and relative free energies of the quadruplexes based on the MD energy analysis. One exception to the general agreement is [d(G(4)T(4)G(4))](2), which had the lowest E(1/2) value, but was determined to be the most stable quadruplex according to the free-energy analysis and ranked fourth based on the RMSD comparison. This discrepancy is attributed to differences in the fragmentation pathway of the quadruplex. PMID- 17719797 TI - Production, characterisation and applicability of monoclonal antibodies to immunoglobulin of Japanese flounder (Paralichthys olivaceus). AB - Immunoglobulin (Ig) of Japanese flounder (Paralichthys olivaceus) was purified by a combination of salting-out and DEAE Sepharose Column chromatography. The purified immunoglobulin had an apparent molecular weight of 74 kDa (heavy chain) and 24 kDa (light chain) in SDS-PAGE. Eighteen hybridomas secreting monoclonal antibodies (MAbs) against Japanese flounder Ig were obtained by immunisation of Balb/C mice with purified Ig preparations, which were selected on the basis of the double indirect enzyme-linked immunosorbent assay (D-ELISA). Two of them designated as 2D8 and 2H1 were cloned by limiting dilution and characterised with western blotting, indirect immunofluorescence assay test (IIFAT) and fluorescence activated cell sorter (FACS) analysis. Under reducing conditions in western blotting, both MAb 2D8 and MAb 2H1 were specific for the heavy chain of Japanese flounder Ig. MAb 2D8 was used to identify surface Ig-positive lymphocytes in the peripheral blood, spleen and pronephros of healthy Japanese flounder by flow cytometry. FACS analysis revealed that 40.48% of lymphocytes in the peripheral blood, 17.32% in the spleen and 9.67% in the pronephros were reactive to 2D8. PMID- 17719796 TI - An in vitro study on the involvement of LINGO-1 and Rho GTPases in Nogo-A regulated differentiation of oligodendrocyte precursor cells. AB - Nogo-A has been considered as one of the most important myelin-associated axonal regeneration inhibitors in the central nervous system. Recent studies have demonstrated various additional physiological roles of Nogo family members. To understand the possible effect of Nogo-A on the differentiation of oligodendrocytes, antibodies against distinct extracellular domains of Nogo-A were applied in cell cultures. Oligodendrocyte precursor cells from P2 rat cortex were grown in the presence of monoclonal antibody against the N-terminal inhibitory domain of Nogo-A or the C-terminal 66 amino acid loop of Nogo-A for 3 days, and the antibody treatment resulted in stunted process extension and inhibited differentiation of oligodendrocytes. Concomitant with morphology changes, Rho GTPases activity was greatly increased upon the antibody treatment and the expression level of LINGO-1, which was recently shown to be a negative regulator for the oligodendrocyte maturation, was upregulated in the process of antibody treatment. These results indicate that endogenous Nogo-A expressed in oligodendrocyte may act though Rho GTPase and LINGO-1 to influence the morphological differentiation of oligodendrocytes and will help us to understand the physiology role of Nogo-A in oligodendrocyte biology. PMID- 17719798 TI - Effects of repeated ankle plantar-flexions on H-reflex and body sway during standing. AB - The study investigated relations between effects of repeated ankle plantar flexion movements exercise on the soleus Hoffmann (H) reflex and on postural body sway when maintaining upright stance. Ten young volunteers performed five sets of ankle plantar-flexions of both lower limbs. Assessment of the feet centre-of pressure (COP) displacement and H-reflex tests were carried out in quiet stance before, during and after the exercise. H-max and M-max responses were obtained in 8 subjects and reported as the peak-to-peak amplitudes of the right soleus muscle electromyographic waves. Mean dispersion of COP along the antero-posterior direction increased significantly during the exercise; whilst the overall H reflex response indicated a reduction without a concomitant modification in the M max response. H-reflex responses, however, varied between participants during the first sets of exercise, showing two main trends of modulation: either depression or early facilitation followed by reduction of the H-reflex amplitude. The extent of reflex modulation in standing position was correlated to the concentric work performed during the exercise (r=0.85; p<0.01), but not to the antero-posterior COP dispersion. These results suggest that during a repeated ankle plantar flexions exercise, modulation of the H-reflex measured in upright stance differs across individuals and is not related to changes of postural sway. PMID- 17719799 TI - A default mode of brain function: a brief history of an evolving idea. AB - The concept of a default mode of brain function arose out of a focused need to explain the appearance of activity decreases in functional neuroimaging data when the control state was passive visual fixation or eyes closed resting. The problem was particularly compelling because these activity decreases were remarkably consistent across a wide variety of task conditions. Using PET, we determined that these activity decreases did not arise from activations in the resting state. Hence, their presence implied the existence of a default mode. While the unique constellation of brain areas provoking this analysis has come to be known as the default system, all areas of the brain have a high level of organized default functional activity. Most critically, this work has called attention to the importance of intrinsic functional activity in assessing brain behavior relationships. PMID- 17719800 TI - Comment on Devlin and Poldrack. PMID- 17719801 TI - Genetic and phenotypic variation among geographically isolated populations of the globally threatened Dupont's lark Chersophilus duponti. AB - Identifying genetically and phenotypically distinct populations of threatened species is critical if we are to delineate appropriate plans for their conservation. We conducted an integrated analysis of population genetic structure, historical demographic events, current gene flow (all based on mtDNA sequences) and morphological variation of three geographically separated groups of populations of Dupont's lark Chersophilus duponti, located in the Iberian Peninsula (three populations), Morocco (two populations), and Tunisia (one population). Unusually, this lark species is the only one among the genus Chersophilus. Our results revealed the early historical divergence of an eastern Dupont's lark lineage (in Tunisia) and a western lineage (in Morocco and Spain), consistent with subspecies taxonomy and distribution. The western lineage subsequently split into two lineages, following the isolation of Iberian and African populations. Such pattern of historical differentiation caused great population genetic structure, with differences among geographic areas explaining more than 80% of total genetic variation. Mismatch distributions and coalescent estimates of divergence time showed that lineage divergence was associated with sudden population expansion events, which apparently took place during the last glaciation, when steppe habitats were widespread across the Mediterranean region. Extant populations from different geographic areas hardly shared any haplotype (only one out of 16 ND2 haplotypes was shared by Tunisian and Moroccan Dupont's larks), and consequently gene flow between geographic areas was found to be virtually absent. Apart from showing great genetic differentiation, Dupont's larks from different geographic areas were morphologically distinct, showing substantial variation in body size and feeding-related traits (length of feet and bill). We conclude that Dupont's lark populations isolated in the Iberian Peninsula, Morocco, and Tunisia are distinct evolutionary entities and should be considered as such in conservation plans. Such circumstance sets a daunting conservation challenge that exemplifies the need of incorporating knowledge of historical processes to our general understanding of the demography of threatened species. PMID- 17719802 TI - Examining a community model of epilepsy care for people with learning disabilities. AB - PURPOSE: To assess the use of specialised medical epilepsy services by people with learning disabilities (LD) and epilepsy in a community healthcare setting, to compare medical epilepsy care in this group to current management guidelines, and to contrast important outcomes with those achieved in different healthcare settings. METHODS: Postal survey with a carer completed questionnaire addressed to all adults with epilepsy registered on an LD register in Sheffield, UK (n=442). RESULTS: An analysis based on 225 returned questionnaires revealed that 22.7% of individuals with LD and epilepsy had been free of seizures for over 1 year. 95.1% were taking antiepileptic drugs (AEDs), 46.2% had had an EEG, and 41.3% a brain scan. 53.3% of diagnoses had been made by epilepsy experts, 38.7% of individuals with LD and epilepsy were under specialist review. Although patients with more severe epilepsy were more likely to be under specialist care, 60.6% of patients with ongoing seizures, 57.9% with major seizures and 68.7% of individuals taken to hospital with prolonged had no access to specialist advice. CONCLUSION: The proportion of people with LD who achieved seizure-control in the described population was lower than in all previously reported studies of LD patient groups. The poor outcome in terms of seizure-control, the lack of access to the epilepsy specialist service, and the apparent under-utilisation of investigations indicate that there are grounds for serious concern about this community model of medical epilepsy care for people with LD. PMID- 17719803 TI - OARSI recommendations for the management of hip and knee osteoarthritis, part I: critical appraisal of existing treatment guidelines and systematic review of current research evidence. AB - PURPOSE: As a prelude to developing updated, evidence-based, international consensus recommendations for the management of hip and knee osteoarthritis (OA), the Osteoarthritis Research Society International (OARSI) Treatment Guidelines Committee undertook a critical appraisal of published guidelines and a systematic review (SR) of more recent evidence for relevant therapies. METHODS: Sixteen experts from four medical disciplines (primary care two, rheumatology 11, orthopaedics one and evidence-based medicine two), two continents and six countries (USA, UK, France, Netherlands, Sweden and Canada) formed the guidelines development team. Three additional experts were invited to take part in the critical appraisal of existing guidelines in languages other than English. MEDLINE, EMBASE, Science Citation Index, CINAHL, AMED, Cochrane Library, seven Guidelines Websites and Google were searched systematically to identify guidelines for the management of hip and/or knee OA. Guidelines which met the inclusion/exclusion criteria were assigned to four groups of four appraisers. The quality of the guidelines was assessed using the AGREE (Appraisal of Guidelines for Research and Evaluation) instrument and standardised percent scores (0-100%) for scope, stakeholder involvement, rigour, clarity, applicability and editorial independence, as well as overall quality, were calculated. Treatment modalities addressed and recommended by the guidelines were summarised. Agreement (%) was estimated and the best level of evidence to support each recommendation was extracted. Evidence for each treatment modality was updated from the date of the last SR in January 2002 to January 2006. The quality of evidence was evaluated using the Oxman and Guyatt, and Jadad scales for SRs and randomised controlled trials (RCTs), respectively. Where possible, effect size (ES), number needed to treat, relative risk (RR) or odds ratio and cost per quality-adjusted life year gained (QALY) were estimated. RESULTS: Twenty-three of 1462 guidelines or consensus statements retrieved from the literature search met the inclusion/exclusion criteria. Six were predominantly based on expert opinion, five were primarily evidence based and 12 were based on both. Overall quality scores were 28%, 41% and 51% for opinion-based, evidence-based and hybrid guidelines, respectively (P=0.001). Scores for aspects of quality varied from 18% for applicability to 67% for scope. Thirteen guidelines had been developed for specific care settings including five for primary care (e.g., Prodigy Guidance), three for rheumatology (e.g., European League against Rheumatism recommendations), three for physiotherapy (e.g., Dutch clinical practice guidelines for physical therapy) and two for orthopaedics (e.g., National Institutes of Health consensus guidelines), whereas 10 did not specify the target users (e.g., Ontario guidelines for optimal therapy). Whilst 14 guidelines did not separate hip and knee, eight were specific for knee but only one for hip. Fifty-one different treatment modalities were addressed by these guidelines, but only 20 were universally recommended. Evidence to support these modalities ranged from Ia (meta-analysis/SR of RCTs) to IV (expert opinion). The efficacy of some modalities of therapy was confirmed by the results of RCTs published between January 2002 and 2006. These included exercise (strengthening ES 0.32, 95% confidence interval (CI) 0.23, 0.42, aerobic ES 0.52, 95% CI 0.34, 0.70 and water based ES 0.25, 95% CI 0.02, 0.47) and nonsteroidal anti-inflammatory drugs (NSAIDs) (ES 0.32, 95% CI 0.24, 0.39). Examples of other treatment modalities where recent trials failed to confirm efficacy included ultrasound (ES 0.06, 95% CI -0.39, 0.52), massage (ES 0.10, 95% CI -0.23, 0.43) and heat/ice therapy (ES 0.69, 95% CI -0.07, 1.45). The updated evidence on adverse effects also varied from treatment to treatment. For example, while the evidence for gastrointestinal (GI) toxicity of non-selective NSAIDs (RR=5.36, 95% CI 1.79, 16.10) and for increased risk of myocardial infarction associated with rofecoxib (RR=2.24, 95% CI 1.24, 4.02) were reinforced, evidence for other potential drug related adverse events such as GI toxicity with acetaminophen or myocardial infarction with celecoxib remained inconclusive. CONCLUSION: Twenty-three guidelines have been developed for the treatment of hip and/or knee OA, based on opinion alone, research evidence or both. Twenty of 51 modalities of therapy are universally recommended by these guidelines. Although this suggests that a core set of recommendations for treatment exists, critical appraisal shows that the overall quality of existing guidelines is sub-optimal, and consensus recommendations are not always supported by the best available evidence. Guidelines of optimal quality are most likely to be achieved by combining research evidence with expert consensus and by paying due attention to issues such as editorial independence, stakeholder involvement and applicability. This review of existing guidelines provides support for the development of new guidelines cognisant of the limitations in existing guidelines. Recommendations should be revised regularly following SR of new research evidence as this becomes available. PMID- 17719804 TI - Extracellular and transmembrane region of a podocalyxin-like protein 1 fragment identified from colon cancer cell lines. AB - Regulated intramembrane proteolysis of membrane proteins has been shown to play an important role in cell differentiation and in the pathogenesis of diseases. The aim of the present study was to identify novel peptides generated by intramembrane proteolysis. The peptides were identified in serum-free cultured (SFC) media from various cell lines by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). A 2315-Da peptide found only in medium from SFC colon cancer cell lines was identified and shown to consist of a portion of both the extracellular and transmembrane regions of human podocalyxin-like 1. This protein fragment was not found in lung or pancreatic cancer cell lines by immunoprecipitation-SELDI tests using an antibody specific to this fragment, suggesting that this human podocalyxin-like protein 1 fragment may be unique to colon cancer cell lines. PMID- 17719805 TI - Re: Secondary medical prevention in patients with peripheral arterial disease. PMID- 17719806 TI - The neurological morbidity of carotid revascularisation: using markers of cellular brain injury to compare CEA and CAS. AB - AIM: This comparative study attempts to evaluate the profile of S-100beta and Neuron-Specific Enolase (NSE), biomarkers of brain injury, in patients undergoing carotid endarterectomy (CEA) and carotid artery stenting (CAS) and to correlate this with haemodynamic and embolic events detected using trans-cranial Doppler (TCD). METHODS: 52 patients with internal carotid artery stenosis requiring intervention were recruited. 24 patients underwent CAS, and 28 underwent CEA. TCD was performed peri-operatively to record mean Middle Cerebral Artery (MCA) velocity and number of High Intensity Transient Signals (HITS) in the MCA of the operated side. Serum was drawn pre-operatively and at six time points in a 48 hour post-operative period, and then assayed using automated commercial equipment. Within and between group variability in markers were assessed by Generalized Estimation Equations modelling. RESULTS: CAS caused more HITS (p=0.028) but less haemodynamic disturbance (p=0.0001) than CEA. Treatment modality (CAS versus CEA) had no direct effect on S-100 changes (p=0.467). NSE levels declined after revascularisation in the CAS group but not after CEA (p=0.002). S-100beta levels rose in patients who had higher numbers of HITS (p=0.002). S-100beta and NSE were not associated with changes in MCA velocity (p>0.5). S-100beta alone increased significantly at 24 hours in those patients with a post-operative neurological deficit (p=0.015). CONCLUSIONS: Trans-cranial Doppler findings suggest that the mechanisms of rise in S-100beta and NSE levels may differ and may be due to increased peri-operative micro-embolisation and cerebral hypoperfusion respectively. Further studies are required to assess the clinical significance of these observed changes. PMID- 17719807 TI - Laparoscopic diagnosis and treatment of aortic vascular prosthetic graft infections in a porcine model. AB - OBJECTIVES: To study the feasibility and efficacy of experimental laparoscopy in the diagnosis of aortic graft infection in pigs. MATERIAL AND METHODS: Eight pigs had an aortic tube graft implanted and inoculated with either 5 x 10(4) or 10(6) CFU of Staphylococcus aureus ATCC 29213. Laparoscopy was performed after a median of 20 days with debridement and sampling for bacterial culture. Thereafter, the grafts were locally soaked in rifampicin and postoperatively, the pigs received rifampicin and ciprofloxacin orally for two weeks and were then sacrificed. RESULTS: All pigs developed graft infection. One pig died from severe clostridial septicaemia before laparoscopy could be performed. The remaining pigs had all samples for bacterial culture taken by laparoscopy from the inflamed tissue. The temperature dropped significantly after laparoscopy, and no macroscopic signs of infection presented at autopsy. However, only culture from one pig was without S. aureus at autopsy. CONCLUSIONS: Laparoscopy is a potential diagnostic tool for aortic graft infection and also affords the opportunity to carry out bacteriological sampling and local antibiotic treatment. The efficacy of laparoscopic treatment needs further evaluation. PMID- 17719808 TI - Smooth muscle dysfunction in patients older than 54 years of age with objective evidence of arteriosclerosis. AB - OBJECTIVE: This investigation was designed to assess the relationship between flow-mediated vasodilatation (FMD) and nitroglycerin (NTG)-mediated vasodilatation (NMD) with atherosclerotic risk factors. METHODS: FMD and NMD were measured in 75 subjects including 57 patients with atherosclerotic disease (AAA/PAOD=30/27, age 72+/-7 years) and 18 controls. Brachial response to hyperemia and NTG were measured every minute after cuff deflation and NTG administration. RESULTS: In the 75 subjects, responses to NTG showed a sigmoid curve. Only 2 cases reached maximal diameter within 4 minutes after NTG, and 90% of the cases reached maximal diameter at 6 minutes or later (7.5+/-2.0 minutes). In patients with atherosclerotic disease, a multiple regression analysis showed higher FMD was associated with higher NMD, and higher NMD was associated with smaller vessel size, lower systolic blood pressure, higher FMD, lower carotid maximal IMT, lower serum levels of insulin, and lower HOMA-IR. CONCLUSIONS: In subjects older than 54, NMD measured at 3 or 4 minutes after NTG administration would underestimate the NTG-dependent vasodilatation. NMD measured with the maximal responded diameter was associated with atherosclerotic risk factors, and it is therefore considered to be an important parameter in patients with atherosclerotic disease. PMID- 17719809 TI - Endovascular ruptured abdominal aortic aneurysm repair (EVRAR): a systematic review. AB - BACKGROUND: To review evidence supporting the use of endovascular ruptured aneurysm repair (EVRAR) for treatment of ruptured abdominal aortic aneurysm (RAAA). METHODS: A systematic review of the medical literature was performed for relevant studies. We searched a number of electronic databases and hand-searched relevant journals until November 2006 to identify studies for inclusion. We considered studies in which patients with a confirmed ruptured abdominal aortic aneurysm were treated with EVRAR, which reported endpoints of mortality and major complications. RESULTS: There was 1 randomised controlled trial (RCT), 33 non randomised case series (24 retrospective and 9 prospective) reports were identified comparing EVRAR (n=891) with conventional open surgical repair for the treatment of RAAA. Whilst no benefit in the primary outcome of mortality was noted in the only RCT, evidence from non-randomised studies suggest that EVRAR is feasible in selected patients, where it may be associated with a trend towards reductions in blood loss, duration of intensive care treatment, early complications, and mortality. CONCLUSIONS: For the treatment of symptomatic or ruptured abdominal aortic aneurysm, emergency endovascular repair (EVRAR) is feasible in selected patients, with early outcomes comparable to best conventional open surgical repair for the treatment of RAAA. PMID- 17719810 TI - Risk models in abdominal aortic aneurysm surgery; useful for policy makers or patients? PMID- 17719811 TI - Induction of laminitis by prolonged hyperinsulinaemia in clinically normal ponies. AB - The purpose of this study was to determine the effects of prolonged administration of insulin, whilst maintaining normal glucose concentrations, on hoof lamellar integrity in vivo on healthy ponies with no known history of laminitis or insulin resistance. Nine clinically healthy, unrelated ponies were randomly allocated to either a treatment group (n =5; 5.9+/-1.7 years) or control group (n =4; 7.0+/-2.8 years). The treatment group received insulin via a euglycaemic hyperinsulinaemic clamp technique modified and prolonged for up to 72 h. Control ponies were infused with an equivalent volume of 0.9% saline. Ponies were euthanized at the Obel grade 2 stage of clinical laminitis and hoof lamellar tissues were harvested and examined for histopathological evidence of laminitis. Basal serum insulin and blood glucose concentrations were 15.7+/-1.8 microU/mL and 5.2+/-0.1 mmol/L, respectively (mean+/-SE) and were not significantly different between groups. Mean serum insulin concentration in treatment ponies was 1036+/-55 microU/mL vs. 14.6 microU/mL in controls. All ponies in the treatment group developed clinical and histological laminitis (Obel grade 2) in all four feet within 72 h (55.4+/-5.5h), whereas none of the control ponies developed laminitis. There was no clinical evidence of gastrointestinal involvement and the ponies showed no signs of systemic illness throughout the experiment. The data show that laminitis can be induced in healthy young ponies, with no prior history of laminitis, by maintaining prolonged hyperinsulinaemia with euglycaemia. This suggests a role for insulin in the pathogenesis of laminitis, independent of hyperglycaemia, or alterations in hind-gut fermentation. For the clinician, early detection and control of hyperinsulinaemia may facilitate management of endocrinopathic laminitis. PMID- 17719812 TI - Perioperative desmopressin prolongs survival in surgically treated bitches with mammary gland tumours: a pilot study. AB - Desmopressin (1-deamino-8-d-arginine vasopressin, also known as DDAVP) is a safe haemostatic compound capable of inhibiting lymph node and lung metastasis in a mouse model of mammary tumour manipulation and surgical excision. The aim of this study was to test the efficacy and safety of perioperative DDAVP (1microg/kg) in surgically treated bitches with mammary gland tumours (MGT). Twenty-one, otherwise healthy, intact bitches, with malignant MGT stage III or IV were randomly allocated to DDAVP (n=11) or placebo (n=10) groups. En bloc mastectomy of the affected gland/s was performed. DDAVP had a significant beneficial effect on disease-free period (P<0.01) and overall survival time (P<0.05). No side effects were seen in any of the cases. Whatever the mechanism of action, it seems that DDAVP may have a novel use in cancer surgery to minimise spread or survival of residual malignant cells. Additional, large scale controlled trials are required to fully evaluate this adjuvant pharmacological protocol. PMID- 17719813 TI - An efficient (1)H/(31)P double-resonance solid-state NMR probe that utilizes a scroll coil. AB - The construction and performance of a scroll coil double-resonance probe for solid-state NMR on stationary samples is described. The advantages of the scroll coil at the high resonance frequencies of (1)H and (31)P include: high efficiency, minimal perturbations of tuning by a wide range of samples, minimal RF sample heating of high dielectric samples of biopolymers in aqueous solution, and excellent RF homogeneity. The incorporation of a cable tie cinch for mechanical stability of the scroll coil is described. Experimental results obtained on a Hunter Killer Peptide 1 (HKP1) interacting with phospholipid bilayers of varying lipid composition demonstrate the capabilities of this probe on lossy aqueous samples. PMID- 17719814 TI - A method for C(alpha) direct-detection in protonless NMR. AB - Attempts are made to efficiently decouple (13)C nuclei without significant loss of coherence during the application of the decoupling package. Such attempts are based on the S(3)E spin-state selection method. A newly developed double S(3)E (DS(3)E) is particularly efficient for C(alpha) detection for proteins as large as 480 kDa. PMID- 17719817 TI - Biodiversity of the species Listeria monocytogenes and the genus Listeria. AB - This review describes the Listeria monocytogenes genome sequences available today and their comparison with that of Listeria innocua and Listeria welshimeri by highlighting their characteristic features and common traits. The diversity present among them is analysed with emphasis on putative virulence and host pathogen interaction related functions. Then large-scale studies comparing gene content of Listeria and how these studies contributed to typing applications will be discussed. Finally, evolutionary conclusions and future perspectives in Listeria genomics are presented. PMID- 17719816 TI - [High fetal irradiation: about one pregnant woman receiving infradiaphragmatic radiotherapy for Hodgkin lymphoma]. AB - We report the case of a 19-year-old young woman for whom was discovered a pregnancy at the end of the irradiation for a Hodgkin lymphoma (stage IV bone Bb), initially treated by chemotherapy. The radiotherapy delivered 36 Gy in infra diaphragmatic volumes (lombo-aortic, spleen, L5), beginning in a pregnant patient for less than 4 amenorrhea weeks. The calculated received fetal dose (literature data, measurement with software TPS, measurement on phantom) is high: it's between 2.8 and 5 Gy. With a current follow-up of 4 years since the radiotherapy's end, the patient is in complete remission and her child presents with a normal development for the age, in spite of the infradiaphragmatic irradiation. PMID- 17719818 TI - Life of Listeria monocytogenes in the host cells' cytosol. AB - In the past decades impressive knowledge has been accumulated concerning the basic mechanisms of interactions between intracellular bacteria and their host cells. Comparatively little is known on the metabolic requirements necessary for efficient replication of these bacteria within their specific host cell compartments. Recent developments in functional genomics have led to more extensive studies of the metabolic aspects that may be crucial for understanding the pathogenesis of intracellular bacteria. Here we summarize our present knowledge on the physiology of L. monocytogenes with emphasis on those parts that seem to be important for its ability to replicate in the cytosol of mammalian host cells. PMID- 17719815 TI - IGFBP-3 sensitizes prostate cancer cells to interferon-gamma-induced apoptosis. AB - OBJECTIVE: Insulin-like growth factor binding protein-3 (IGFBP-3) has been shown to exhibit diverse biological actions, including IGF-independent effects on cell growth and cell death. Here we report that IGFBP-3 sensitizes prostate cancer cells to interferon-gamma (IFN-gamma)-induced apoptosis and inhibition of cell proliferation. DESIGN: The cell growth or cell death of prostate cells in response to the treatments of IGFBPs and/or IFN-gamma was measured, and the signaling pathways mediating these actions assessed. RESULTS: Cell proliferation was minimally affected when M12 prostate cancer cells were treated with exogenous IGFBP-3 (1-5 microg/ml), IGFBP-1 (1-5 microg/ml) or IFN-gamma (20 U/ml). However, strong inhibition of cell growth and significant apoptosis were observed when M12 cells were co-treated with IGFBP-3 and IFN-gamma, but not with IGFBP-1 and IFN gamma. These effects were IGF-independent and appear not to require intracellular localization of IGFBP-3, as similar results were obtained with mutants of IGFBP-3 that either could not bind IGF or has impaired ability to be internalized. Further analyses revealed that IGFBP-3, but not IGFBP-1, could significantly enhance the weak tyrosine phosphorylation of STAT1 induced by IFN-gamma (20 U/ml) alone. The IGFBP-3-promoted apoptosis in the presence of IFN-gamma could also be abrogated by blockade of the mTOR pathway with its pharmacological inhibitors, LY294002 or rapamycin. CONCLUSIONS: These results demonstrated that in a cancer cell line not responsive to exogenous IGFBP-3 alone, IGFBP-3 sensitized the cells to the anti-proliferative, proapoptotic actions of IFN-gamma through an IGF independent, STAT1- and mTOR-dependent mechanism. PMID- 17719819 TI - Antisynthetase syndrome in a patient with ankylosing spondylitis. PMID- 17719820 TI - [What materials for hysteroscopic metroplasty?]. PMID- 17719821 TI - [Uterine malformations and reproduction]. AB - The frequency of uterine malformations impacting on reproduction seems not easy to determine. Their diagnosis needs specific explorations (hysterosalpingography, hysteroscopy and laparoscopy). Spontaneous fertility may be impaired in relation with uterine abnormalities. All these abnormalities could have repercussions on the conceptus' evolution like abortion, preterm delivery, vascular pathologies and intrauterine growth restriction. Ovarian function does not seem to be altered even though implantation rate could be reduced. Surgery, especially endoscopy, allows a precise diagnosis, a prognostic evaluation and an adequate treatment improving conception rates and pregnancy outcome. Mainly hysteroscopic septum section and expansion metroplasty were regularly described. PMID- 17719822 TI - [Intrauterine insemination: against systematic ovarian stimulation]. AB - Intrauterine insemination is a technique proposed of first intention in many situations of non-tubal infertilities. It is very frequently associated with a stimulation of ovulation, with the objective of precisely synchronizing the intra uterine stimulation and ovulation, and an increase in follicular recruitment. If intrauterine stimulation is often a determining factor in obtaining pregnancy, stimulation of ovulation does not always bring about an obvious benefit and its interest must be discussed according to the indications, knowing on the other hand that it is determining in the occurring of multiple pregnancies. PMID- 17719823 TI - [Septate uterus: role of hysteroscopic metroplasty]. AB - The uterus septum is the most frequently encountered uterine malformation. The prevalence of the uterine septa in the infertile patients is estimated at approximately 1%. On the other hand, it increases to reach 3,3% among women presenting repeated fetal losses. The objective of this article is to propose an updating of the data of the literature concerning the cure of uterine septa by hysteroscopic metroplasty. Operative hysteroscopy, with its simplicity, its reproducibility and its low morbidity between the hands of a trained operator, remains the gold standard treatment of the uterine partitions. The abortive disease always constitutes the main indication of the cure of septum. In the infertile patients, a metroplasty seems to be legitimate in the following situations: women more than 35 years old; unexplained infertility, resistant to any technique of assisted reproduction; discovery of a uterine septum at the time of the coelioscopy and the diagnostic hysteroscopy realized within the framework of an assessment of infertility; patients for whom it is assumed that Assisted reproductive technique (ART) is needed; women with past obstetrical history. The complications related to the hysteroscopic metroplasty are not very frequent. However, the hysteroscopic resection of a uterine septum could expose later to the risk of uterine rupture. PMID- 17719824 TI - [Intraperitoneal chemotherapy in ovarian cancer]. AB - Ovarian cancer represents 4500 new cases a year in France and the prognosis of such tumor is not yet clear, even for the early stages. This is notably owing to the amount and size of peritoneal tumor residual. Recently, five therapeutic trials were published concerning the intra-peritoneal chemotherapy of ovarian cancer stage III in patients to whom an optimal debulking surgery had been done. These studies were variable in there outcome showing on the one hand, either the absence of significant difference or a significant lengthening of both total life duration and life without recurrence during the period of treatment with intra peritoneal chemotherapy. On the other hand, there was a significant increase in hematological toxicity and temporary impairment of the quality of life during intra-peritoneal treatments. There were also complications linked to the intra peritoneal catheter, which led to the termination of the treatment protocol in some cases. However, results showed a mattering benefit of survival in spite of a notable rate of incomplete treatment protocols. These results have demonstrated the necessity to consider the intra-peritoneal adjuvant chemotherapy as a treatment option in patients with epithelial ovarian cancer stage III. Patients must be highly selected and well counseled, in order to go for this treatment option after receiving optimal debulking surgeries. PMID- 17719825 TI - [Diethylstilbestrol exposure in utero. Polemics about metroplasty. The cons]. AB - Uterine malformations in DES-exposed women are not the only aetiologies for infertility, miscarriages, and other problems in their reproductive life. A global screening of fertility factors of the couple may, for instance, show in them vascular uterine abnormalities which reduce their reproductive potential. Furthermore, these abnormalities are not always predictive of losses of pregnancy, and many exposed women with patent uterine abnormalities can carry a pregnancy to term. Metroplasty for uterine enlargement is a surgical procedure suggested for restoring the size and shape of the uterine cavity. There are no comparative studies for assessing efficacy and safety of metroplasty. Therefore, metroplasty should not be performed routinely, but should only be considered after the couple has undergone a full fertility workup, and the best possible level of fertility has been achieved. PMID- 17719826 TI - [Assisted reproductive care in serodiscordant couples whose man is infected with HIV]. AB - Serodiscordant couples whose man is infected by human immunodeficiency virus have actually induced sterility by condom use. Since 2001, in France, assisted reproduction in serodiscordant couples has been facilitated thanks to the decree of 10th May 2001. In spite of the immense social and scientific advances in Assisted Reproductive Techniques, in such couples, limitation of care remains in certain cases. This study reviews current practices in France and other countries. Limits due to present reproductive and virological methods or legal conditions are underlined. In agreement with current scientific knowledge we suggest new modalities of reproductive care in serodiscordant couples with HIV infected men. PMID- 17719827 TI - The role of skirt geometry of dental crowns on the mechanics of failure: experimental and numerical study. AB - Dental crown structures were modelled using a curved bi-layer system consisting of a brittle glass coating on a compliant polymeric substrate, to illustrate the role of skirt geometry on the mechanics of failure evolution. The geometries of the samples were varied by tapering the skirts of the glass shells in different lengths and thicknesses. The failure of these samples was investigated under single-cycle axial loading tests using an indenter of low elastic modulus. The onset of fracture was observed in situ using a video camera. A relationship between the height and thickness of the taper and the critical load required for a crack to appear in the sample was observed. Margin cracks were observed to propagate from flaws near the margins. Experimental trends suggested that critical loads increased with increasing taper thickness, and decreased with increasing taper length. Finite element modelling was also used to evaluate the stress distribution in the glass coating. Peak maximum principal stresses at the margins decreased with increasing taper thickness, and increased with increasing taper length, consistent with the experimentally determined critical loads. It is concluded that long, narrow tapers should be avoided in order to maximise the load bearing capacity of dental crowns. PMID- 17719828 TI - Anxiety and depression: main determinants of health-related quality of life in Brazilian patients with Parkinson's disease. AB - Determinants of health-related quality of life (HRQoL) were assessed in 115 Brazilian patients (56.5% males; mean age 62.5 years) with Parkinson's disease (PD). Hoehn and Yahr (H&Y) staging, Scales for Outcomes in Parkinson's Disease Motor Scale (SCOPA-MS), Cumulative Illness Rating Scale-Geriatrics, Hospital Anxiety and Depression Scale (HADS), Parkinson's Disease Questionnaire (PDQ-39), and SCOPA-Psychosocial Questionnaire (SCOPA-PS) were applied. Median H&Y was 3 and the SCOPA-MS score was 25.6+/-13.1. The proportion of patients who scored > or =11 points in the HADS-Depression and HADS-Anxiety subscales were 47% and 30.4%, respectively. In the multivariate model, HADS-Anxiety or HADS-Depression (p<0.0001), disability (SCOPA-MS II) (p=0.0001) and comorbidity (p=0.0005) were independently associated to PDQ-39 and SCOPA-PS. Mood disturbances were the main determinants of HRQoL. PMID- 17719829 TI - WW domains 2 and 3 of Rsp5p play overlapping roles in binding to the LPKY motif of Spt23p and Mga2p. AB - Rsp5p of Saccharomyces cerevisiae is a member of the C2-WW-HECT family of ubiquitin ligases and it interacts with targets via its WW domains. Spt23p and Mga2p are Rsp5p substrates and Rsp5p activates the OLE1 inducing functions of these membrane-localized transcription factors by ubiquitination. Although it is known that Rsp5p binds Mga2p and Spt23p via an imperfect WW domain-binding site (LPKY) that is located within the carboxy-terminal domain of the proteins, it remains unclear which WW domains mediate binding. We show that Rsp5p mutants harboring mutations in single WW domains are Spt23p/Mga2p binding and ubiquitination proficient. This is also the case for WW domains 1/2 and WW domains 1/3 mutants. However, disrupting WW domains 2 and 3 abrogates a physical and functional interaction with substrates in vitro and in cells. We also show that abrogation of WW domains 2 and 3 eliminates the activity of an Rsp5p dominant-negative mutant and an rsp5 WW domain 2/3 mutant is unable to rescue the proliferative defects of rsp5 Delta cells. Interestingly, while rsp5 Delta cells are able to grow on oleic acid containing YPD media, they as well as those transformed with the WW domain 2/3 mutant are unable to proliferate on oleic acid containing synthetic drop-out media. We conclude from these studies that WW domains 2 and 3 of Rsp5p play overlapping roles in binding to the LPKY site on Spt23p and Mga2p. Also, we propose that WW domains 2 and 3 perform yet to be defined essential function(s) outside of the OLE1 pathway when cells are grown in nutrient restrictive media. PMID- 17719830 TI - Bone marrow transplantation into hemochromatotic mice decreases hepatic and duodenal iron overload. AB - Human hereditary hemochromatosis is a disorder of iron homeostasis characterized by increased absorption of iron and its deposition in parenchymal organs. The maintenance of iron homeostasis is regulated by molecules involved in the absorption, transport, storage and redox of iron. The potential of hematopoietic stem cell therapy for liver diseases has been studied in some experimental animal models. Our objective was to evaluate the effect of bone marrow transplantation from wild type mice on the status of iron overload in Hfe knockout hemochromatotic mice (Hfe(-/-)). The transplanted cells were detected in the liver (11% of the total cells) and characterized as hepatocytes and myofibroblasts. They were also detected in the duodenum and characterized as myofibroblasts. The iron content in the Hfe(-/-) mice descended 2.9-fold in the liver and 2.4-fold in the duodenum 6 months after transplantation. Non significant changes of relative mRNA abundance of genes of iron metabolism were observed in the liver and duodenum of Hfe(-/-) transplanted mice. At 6 months after transplantation the proportion of Hfe mRNA in Hfe(-/-) mice reached 3.8% of the levels in wild type mice in the liver and 1.6% in the duodenum. In conclusion, adult stem cells from bone marrow transplant were able to differentiate into hepatocytes and myofibroblasts in hemochromatotic mice. Bone marrow transplantation assisted in reducing the iron overload in this murine model of hemochromatosis. These findings might contribute to the knowledge of pathways involved in the regulatory system of iron homeostasis. PMID- 17719833 TI - Novel throughput phenotyping platforms in plant genetic studies. AB - Unraveling the genetic basis of complex traits in plants is limited by the lack of appropriate phenotyping platforms that enable high-throughput screening of many genotypes in multilocation field trials. Near-infrared spectroscopy on agricultural harvesters and spectral reflectance of plant canopies have recently been reported as promising components of novel phenotyping platforms. Understanding the genetic basis of complex traits is now within reach with the use of these new techniques. PMID- 17719831 TI - Mammary epithelial cell: influence of extracellular matrix composition and organization during development and tumorigenesis. AB - Stromal-epithelial interactions regulate mammary gland development and are critical for the maintenance of tissue homeostasis. The extracellular matrix, which is a proteinaceous component of the stroma, regulates mammary epithelial growth, survival, migration and differentiation through a repertoire of transmembrane receptors, of which integrins are the best characterized. Integrins modulate cell fate by reciprocally transducing biochemical and biophysical cues between the cell and the extracellular matrix, facilitating processes such as embryonic branching morphogenesis and lactation in the mammary gland. During breast development and cancer progression, the extracellular matrix is dynamically altered such that its composition, turnover, processing and orientation change dramatically. These modifications influence mammary epithelial cell shape, and modulate growth factor and hormonal responses to regulate processes including branching morphogenesis and alveolar differentiation. Malignant transformation of the breast is also associated with significant matrix remodeling and a progressive stiffening of the stroma that can enhance mammary epithelial cell growth, perturb breast tissue organization, and promote cell invasion and survival. In this review, we discuss the role of stromal-epithelial interactions in normal and malignant mammary epithelial cell behavior. We specifically focus on how dynamic modulation of the biochemical and biophysical properties of the extracellular matrix elicit a dialogue with the mammary epithelium through transmembrane integrin receptors to influence tissue morphogenesis, homeostasis and malignant transformation. PMID- 17719834 TI - The mechanical response of human liver and its relation to histology: an in vivo study. AB - The mechanical response of human liver is characterized in vivo by means of intra operative aspiration experiments. Mechanical characterization is combined with histological evaluation of liver tissue biopsies obtained from the resected liver at the site of mechanical testing. This procedure enables a quantitative analysis of the correlation between mechanical response and tissue micro-structure of normal and diseased liver. Ten organs were tested in vivo at multiple locations, as well as ex vivo immediately after resection. Biopsies were analyzed in terms of pathology and percentage of connective tissue content. The change of the mechanical parameters from in vivo to ex vivo has been determined, with an increase of 17% of the proposed stiffness index. The relationship between mechanical parameters and various pathologic conditions affecting the tissue samples has been quantified, with fibrosis leading to a response up to three times stiffer as compared with normal tissue. Increased stiffness can be detected by digital palpation (increased "consistency") and may suggest the presence of a tumor. The present observations suggest that stiffness increase cannot be attributed to the tumoral tissue itself, but rather to the fibrotic stroma that often arise within or adjacent to the tumor. Variation of the mechanical parameters as a function of connective tissue content has been evaluated based on the histological examinations and the results confirm a direct proportionality between stiffness index and connective tissue percentage. The approach described here might eventually lead to a diagnostic procedure and complement other clinical methods, like palpation and ultrasound examination of the liver. PMID- 17719835 TI - Atypical manifestation of upper lid margin staining in silicone hydrogel lens wearers with symptoms of dry eye. AB - PURPOSE: To report an atypical manifestation of upper lid margin staining (ULMS) that occurred in adapted silicone hydrogel (SH) contact lens wearers who complained of ocular surface dryness. METHODS: Sequential staining with sodium fluorescein (FL) and lissamine green (LG) strips was performed in 38 SH lens wearers. The "wiper area" of the upper lid was examined with the slit lamp, at 8x and 12x magnifications. RESULTS: Four out of 38 subjects (10.5%) showed fimbriated or "feathery" extensions from the superior margin of the subtarsal fold onto the upper tarsal plate. The extent of these feathery extensions varied between subjects, with a mean (+/-S.D.) length of 2+/-0.8 mm. In all cases a broad band of staining with both FL and LG was demonstrated, which extended along the entire length of the lid margin. CONCLUSION: The staining patterns shown on the subjects' upper lid margins and tarsal plates suggest that ULMS may include more complex variants. The putative tissue damage revealed through the staining, points to a mechanism not simply restricted to the upper lid margin. PMID- 17719836 TI - Assessment of cytotoxicity and DNA damage exhibited by siloranes and oxiranes in cultured mammalian cells. AB - The potential reactivity and structural properties of oxiranes (epoxides) are advantageous when considering polymers for medical devices. However, epoxy compounds are widely known to have genotoxic properties. The objective of the study was to evaluate the cytotoxicity and primary DNA damage effects induced by oxiranes and siloranes, silicon containing oxiranes. The siloranes, Ph-Sil, Tet Sil, and Sil-Mix and the oxiranes Cyracure UVR-6105 and 1,3-bis[2-(2 oxiranylmethyl) phenoxy]pentane (OMP-5) were dissolved in organic solvents and dilutions containing less than 0.5% solvent were used in biological assays. The concentration that reduced the viability of 50% (TC(50)) of L929 cells was measured using the MTT assay and guided the selection of subtoxic doses for evaluation of DNA damage. Ph-Sil was more cytotoxic than OMP-5, Cyracure UVR-6105 and Sil-Mix. However, the TC(50) value of Tet-Sil could not be determined due to its poor solubility. DNA damage was evaluated in the sister chromatid exchange (SCE) assay with CHO cells, and the alkaline comet assay with L929 cells. In contrast to the siloranes, the oxiranes exhibited significant increases (p>0.05) in SCE frequencies and DNA migration relative to their solvent controls. Our findings support previous reports that siloranes have low genotoxic potential and can be suitable components for development of biomaterials. PMID- 17719837 TI - Mixed-ligand Ru(II) complexes with 2,2'-bipyridine and tetradentate Schiff bases auxiliary ligands: Synthesis, physico-chemical study, DFT analysis, electrochemical and Na+ binding properties. AB - cis-Bis(2,2'-bipyridyl)dichlororuthenium(II)dihydrate complexed with Schiff bases salen (L1H2) and salophen (L2H2) provides complexes of compositions [Ru(L1)(bpy)2] 1 and [Ru(L2)(bpy)2] 2, respectively with cavity. The structure of these complexes characterized by spectroscopic studies were supported by their optimized geometries based on DFT calculations. Complexes 1 and 2 were then allowed to interact with methanolic solution of sodium perchlorate separately providing corresponding complexes 3 and 4 with the compositions 1.NaClO4 and 2.NaClO4, respectively. The formation constants were then evaluated by monitoring the changes in their UV-visible spectral features upon addition of different amount of sodium salts in the presence of a fixed concentration of the ruthenium complexes at a wavelength 294 nm. Emission (solution), luminescence microscopic and cyclic voltammetric studies of these complexes have also been made. PMID- 17719838 TI - Highly sensitive and selective spectrophotometric and spectrofluorimetric methods for the determination of ropinirole hydrochloride in tablets. AB - Three sensitive, selective, accurate spectrophotometric and spectrofluorimetric methods have been developed for the determination of ropinirole hydrochloride in tablets. The first method was based on measuring the absorbance of drug solution in methanol at 250 nm. The Beer's law was obeyed in the concentration range 2.5 24 microg ml(-1). The second method was based on the charge transfer reaction of drug, as n-electron donor with 7,7,8,8-tetracyanoquinodimethane (TCNQ), as pi acceptor in acetonitrile to give radical anions that are measured at 842 nm. The Beer's law was obeyed in the concentration range 0.6-8 microg ml(-1). The third method was based on derivatization reaction with 4-chloro-7-nitrobenzofurazan (NBD-Cl) in borate buffer of pH 8.5 followed by measuring the fluorescence intensity at 525 nm with excitation at 464 nm in chloroform. Beer's law was obeyed in the concentration range 0.01-1.3 microg ml(-1). The derivatization reaction product of drug with NBD-Cl was characterized by IR, 1H NMR and mass spectroscopy. The developed methods were validated. The following analytical parameters were investigated: the molar absorptivity (epsilon), limit of detection (LOD, microg ml(-1)) and limit of quantitation (LOQ, microg ml(-1)), precision, accuracy, recovery, and Sandell's sensitivity. Selectivity was validated by subjecting stock solution of ropinirole to acidic, basic, oxidative, and thermal degradation. No interference was observed from common excipients present in formulations. The proposed methods were successfully applied for determination of drug in tablets. The results of these proposed methods were compared with each other statistically. PMID- 17719839 TI - From a conceptual problem-oriented electronic patient record model to running systems: a nationwide assessment. AB - BACKGROUND: The development of problem-oriented conceptual models for electronic patient record (EPR) systems can improve data communication between health professionals. But little has been done so far to investigate to what extent it is possible to implement such models in operational EPR systems. OBJECTIVE: In this paper, we measure the conformance between a conceptual model and the various ways it is implemented within general practitioners' (GPs') electronic patient records. METHODS: We started from a simple problem-oriented conceptual model and we defined an original discriminating method to assess its implementation. This method is scenario-based (dummy patient), functional, and relative (comparison between software systems). Each implementation is assessed by two evaluators and the final result is a "success/failure" score. The assessment was performed within the scope of the official Belgian accreditation procedure for GPs' electronic patient records, which is voluntary, publicly funded, and based on a dynamic quality improvement paradigm. Almost all Belgian GPs' software systems (17) were assessed. The robustness of our results was assessed through a sensitivity analysis. RESULTS: We found that 65% (11/17) of the software systems currently used succeeded in implementing the problem-oriented conceptual model with a high confidence level (error rate<10%). The results were widely accepted by the software developers. CONCLUSIONS: A problem-oriented conceptual model can be successfully implemented in many operational EPR systems. The quality of the implementation can be assessed. Our results could be used at the international level to improve semantic interoperability between patient information systems, for instance in relation to broader conceptual models such as the European CONTsys pre-norm. PMID- 17719840 TI - Idiopathic dilated cardiomyopathy exhibits defective vascularization and vessel formation. AB - BACKGROUND: Ultrastructural findings of idiopathic dilated cardiomyopathy (IDCM) include myocyte atrophy and myofilament loss, yet little is known about the vascular abnormalities present in IDCM. METHODS AND RESULTS: Patients with IDCM and controls underwent multi-slice CT to examine length and diameter of epicardial vasculature. The levels of mobilizing cytokines and circulating EPCs were assessed by endothelial colony formation assay and flow cytometry. Immunohistochemistry and Western blot were used to examine microvessel density and expression of HIF-1alpha and beta-catenin. Main epicardial coronary arteries were shorter and smaller, and microvascular density was reduced in the epicardium in IDCM. Epicardial vessel paucity was associated with increased numbers of HIF 1alpha(+) cells (46.8+/-13.1% vs. 19.4+/-9.4%, p=0.006) indicating local epicardial hypoxia and elevation of circulating VEGF-A (394 pg/mL vs. 22 pg/mL, p=0.001). The number of mobilized progenitors CD133(+)/VEGF-R2(+) was 21-fold higher in IDCM compared with controls (6.5+/-3.3% vs. 0.3+/-0.2%; p<0.001). Moreover, this defective vascularization was associated with reduced myocardial expression of vascular beta-catenin, an important angiogenic regulator. CONCLUSIONS: This study shows defective vascularization and impaired vasculogenesis (the de novo vascular organization of mobilized endothelial progenitors) and angiogenesis (by which new blood vessels are formed from pre existing mature endothelial cells) in human IDCM. PMID- 17719843 TI - Sterol methenyl transferase inhibitors alter the ultrastructure and function of the Leishmania amazonensis mitochondrion leading to potent growth inhibition. AB - We describe here the effects of Delta(24(25)) sterol methenyl transferase inhibitors (SMTI) on promastigote and axenic amastigote forms of Leishmania amazonensis. When these cells were exposed to 20-piperidin-2-yl-5alpha-pregnan 3beta-20-diol (22,26-azasterol; AZA), hydrazone-imidazol-2-yl-5alpha-pregnan 3beta-ol (IMI), 20-hydrazone-pyridin-2-yl-5alpha-pregnan-3beta-ol (PYR) or 24(R,S),25-epiiminolanosterol (EIL), a concentration- and time-dependent inhibition of growth was observed, with IC(50) values in the sub-micromolar range. Ultrastructural alterations in treated cells were mainly observed in the mitochondrion, which displayed an intense swelling and a reduction of the electron density of the matrix with remarkable changes in the inner mitochondrial membranes. Mitochondrial transmembrane electric potential (DeltaPsi) was measured using spectrophotometric methods in control and treated promastigotes permeabilized with digitonin. After energization with the substrates for complexes I, II or IV of the respiratory chain, it was possible to detect marked changes of DeltaPsi in promastigotes treated with 1 microM of the SMTI for 48 or 72 h when compared with normal cells, indicating that these compounds led to the loss of the energy-transducing properties of the mitochondrial inner membrane, probably related to the alteration of its lipid composition. The present study confirms these findings, showing that in Leishmania amazonensis the mitochondrial complex appears to be the first organelle affected after treatment with different SMTI. PMID- 17719844 TI - Bioaerosols--sources and control measures. AB - In every field of activity where organic material is being handled, emissions of dust, gases, odor as well as bioaerosols are bound to arise. For this reason, waste management facilities or else agricultural enterprises are potential emission sources of bioaerosols. The dispersion of bioaerosols from waste treatment facilities and their health impacts continue to be the subject of numerous discussions. This article addresses organizational and engineering measures for the mitigation of bioaerosol emissions. The required scale of emission reduction and the choice of microbiological parameters have to be assessed with respect to location and facility type. PMID- 17719846 TI - Self-perceived health space and geographic areas in Switzerland. AB - Self-perceived health is an important characteristic for the investigation of public health questions. Based on health characteristics from the 1997 Swiss Health Survey, the relationship between health perception and geographic areas in Switzerland was analysed. Using an explorative data analysis, categorical principal component analysis, a two-dimensional 'health space' was created, using 16 items of self-reported health. The first dimension of this health space represents 'general health', the second dimension contrasts 'mental and physical symptoms'. Into this health space, five different Swiss area typologies were projected. The area types showed distinct 'localities' within the health space, which vary with regard to the magnitude of age and gender differentiation. This type of visualising or 'mapping' of area types within health space has not previously been conducted. PMID- 17719845 TI - Vulnerability to air pollution health effects. AB - INTRODUCTION: Ambient air pollution can have adverse effects on the health of exposed populations, but individuals or groups are not equally vulnerable, and pollution reduction benefits are likely to be unevenly distributed within a population. While the use of total-population risks is a valid approach for public health protection, it is increasingly recognized that more attention on vulnerable groups is necessary. This paper describes population vulnerability to the health effects of air pollutants using risk analysis concepts and based on available evidence. METHODS: Publications reporting air pollution health risks for specific sub-populations, or more conceptual discussions of vulnerability, were selected following a literature search of the PubMed database. Only studies in the context of developed countries were included. Information on population characteristics and factors that can influence risk was assessed from the perspective of the vulnerability framework, and was used to outline interactions with biological susceptibility, exposure, and social coping. RESULTS: Population characteristics encompass several factors that interact and confer vulnerability. Age, for example, regarded as significant mostly in terms of physiology, also relates to exposure through behaviours and activities that can be more amenable to prevention. Children are recognized as a high-risk group but their vulnerability may differ by childhood stage, while pregnant women are not explicitly identified as a vulnerable group despite growing evidence for reproductive risks. Social-economic factors have received little attention, although they can affect coping capacity as well as interact with susceptibility and exposure to air pollution. CONCLUSIONS: Evidence for vulnerability components often lies in different fields of study and has not been evaluated in an integrated manner. Better understanding of population vulnerability can improve the scientific basis to assess risks and develop policies or other health protection initiatives to reduce the impacts of air pollution. PMID- 17719847 TI - The influence of body position on leg kinematics and muscle recruitment during cycling. AB - The effects of upper body orientation on neuromuscular control of the leg during cycling are not well understood. Our aim was to investigate the effects of upper body orientation on control of movement of distal leg segments during cycling. We compared three-dimensional leg and foot kinematics and muscle recruitment patterns between upright and aerodynamic riding positions. Comparisons were made between 10 elite cyclists, 10 elite triathletes and 10 novice cyclists. We found that upper body orientation did not influence kinematics of the leg and foot or primary muscle activity (i.e., the main bursts of muscle activity). The aerodynamic riding position was, however, associated with less modulation of muscle activity (i.e., less relaxation of the muscle during secondary muscle activity) and greater coactivity in elite triathletes and novice cyclists. Our results suggest that orientation of the upper body influences neuromuscular control of the leg during cycling in elite triathletes and novice cyclists. The change in muscle recruitment (i.e., the change in how the goal movement was achieved) implies that the ability of the central nervous system to execute the cycling movement in the most skilled manner was adversely influenced by upper body orientation in elite triathletes and novice cyclists. Less modulation of muscle activity and greater coactivation in elite triathletes when cycling in the aerodynamic position, and the similarity of changes shown in elite triathletes and novice cyclists, may be interpreted as further evidence of less skilled control of movement in elite triathletes when compared to cyclists matched for cycling training history. PMID- 17719848 TI - Simulated rugby performance at 1550-m altitude following adaptation to intermittent normobaric hypoxia. AB - Team-sport athletes who normally reside at sea level occasionally play games at altitudes sufficient to impair endurance performance. To investigate the effect of intermittent normobaric hypoxic exposure on performance in generic and game specific tests at altitude, 22 senior club level rugby players performed baseline tests before single-blind random assignment to one of three groups: hypoxia altitude (n=9), normoxia-altitude (n=6), and normoxia-sea level (n=7). The hypoxia-altitude group underwent 9-13 sessions of intermittent hypoxic exposure (concentration of inspired oxygen=13-10%) over 15 days, then repeated the performance tests within 12h of travelling to 1550m. The normoxia-altitude group underwent placebo exposures by breathing room air before repeating the tests at altitude, whereas the normoxia-sea level group underwent placebo exposures before repeating the tests at sea level. Hypoxic exposure consisted of alternately breathing 6min hypoxic gas and 4min ambient air for 1h at rest. Performance measures gathered at each testing session were maximum speed, sub-maximum heart rate speed and sub-maximum lactate speed during a 20-m incremental running test, mean time in six 70-m sprints, repetitive explosive power and other measures from seven 5.5-min circuits of a rugby simulation. Repetitive explosive power ( approximately -16%) and 20-m shuttle performance ( approximately -3%) decreased substantially at altitude compared to sea level. Acclimatisation to hypoxia had a beneficial effect on sub-maximum heart rate and lactate speed but little effect on other performance measures. In conclusion, 1550-m altitude substantially impaired some measures of performance and the effects of prior adaptation via 9 13 sessions of intermittent hypoxia were mostly unclear. PMID- 17719849 TI - For debate: should observational clinical studies require ethics committee approval? AB - All forms of management in medicine involve weighing up: (1) the potential benefits or efficacy of treatment (2) the potential side effects of treatment and (3) the costs or cost-effectiveness of treatment. It is well established that the randomised control trial (RCT) is the gold standard for determining treatment efficacy and it is obvious why RCTs should be subjected to ethical screening. However, RCTs are not the best methodology for every study, particularly as they are so expensive to conduct. Observational studies are particularly valuable for studying side effects and cost-effectiveness of treatment and still have value (albeit of a lesser quality) in assessing treatment efficacy. Most observational clinical studies are not ethically sensitive and, if it is agreed that therefore ethics committee screening is therefore not required for these studies, they can be completed at low cost with minimal need for industry sponsorship. Universal ethics committee requirements for all observational clinical papers would act as an unnecessary barrier to obstruct the publication of useful studies. Paradoxically, the need in many cases to seek industry funding to cover the extra expense for such a requirement would probably make observational studies less ethically sound. PMID- 17719850 TI - Evaluation of educational preparation for cancer and palliative care nursing for children and adolescents in England. AB - This paper reports the findings of a study which was carried out to evaluate the educational preparation of cancer and palliative care nurses in England. The study was carried out in three stages and covered the following areas; documentary analysis of curriculae, assessment of practice, patients and professionals views of threshold and expert practice. The findings suggested that although there was widespread compliance with a national standard for cancer nursing, this was not the case for palliative care nursing. There was uncertainty about what should be assessed in practice and ambiguity about what was actually assessed. Partnership with children and their parents, clinical skills, multi disciplinary working, and personal attributes were the main foci for expectations of threshold practice but an expert panel had difficulty in describing the attributes of higher level practice. The paper also describes how some of recommendations from the study are being taken forward in current policy and practice. PMID- 17719851 TI - Issues and challenges in nursing and nursing education in Japan. AB - In this editorial we discuss the challenges and issues in nursing and nurse education in Japan. These include a rapid growth in the number of universities offering nursing programs without sufficient time for preparation of faculty; issues in the traditional ways of teaching in classrooms; the appearance of nursing shortages in a country with the highest rate of longevity in the world; and the position of nursing faculty in a society that is largely male dominated. PMID- 17719852 TI - Rapid recombination screening to test gene essentiality demonstrates that pyrH is essential in Mycobacterium tuberculosis. AB - The availability of the complete genome of Mycobacterium tuberculosis affords the possibility of screening genes for essentiality under defined conditions. We tested a rapid recombination method for screening and confirmation of gene essentiality which would be more amenable to higher throughput applications. Non replicating vectors carrying the internal portion of a gene were used as recombination substrates. Such vectors would lead to inactivation of the target gene in a single recombination step. For non-essential genes, recombinants can be obtained; for essential genes, no recombinants can be obtained, thus providing a rapid screening method to determine essentiality in a targeted manner. The incorporation of a promoter in the vector allowed us to establish the essentiality of a single gene in an operon. We confirmed this method worked with several essential (proC, glnE, mtrB, trpD) and one non-essential (tlyA) gene. In addition, we used the method to demonstrate that the pyrH gene is essential. PMID- 17719853 TI - Errors in EEGs and the misdiagnosis of epilepsy: importance, causes, consequences, and proposed remedies. PMID- 17719854 TI - Selective pressures of human immunodeficiency virus type 1 (HIV-1) during pediatric infection. AB - Pediatric HIV-1 infection presents remarkable features that are distinct from those observed in adult infection. In vertically HIV-1-infected children, the viral load declines more slowly, and the cytotoxic T-lymphocyte response emerges late, only after the sixth month of life. This response generally tends to be narrow and less intense than that seen in adults. While the nuances of immune response at the cellular level during pediatric HIV-1 infection have been addressed, there is a lack of studies focusing on the consequences of this delayed and narrowed immune response at the population level. To better explore these features, we evaluated the selection regimen in gag, pol and env gene fragments of HIV-1 during pediatric infection. We estimated the number of nonsynonymous substitutions (d(N)) and synonymous substitutions (d(S)) codon-by codon, using the maximum likelihood method and a modified counting method. Notably, both methods indicated a similar intensity of selection (measure by mean d(N)/d(S) ratio) between children and adults. Additionally, sites under positive selection were equally distributed along HIV genes and the location of these sites was analogous between children and adults. Therefore, the selective regimen in HIV during pediatric infection is equally broad and intense likewise the observed in adults. Unexpectedly, our phylogenetic-based analysis enabled us to identify two regions in the env gene of HIV with distinct adaptive functions. The first region, located in the vicinity of V3 loop, contains sites that might increase viral fitness within-host during antibody attack and virus-cell interaction. The second region, restricted to amino acids 334-368 of Gp160, contains sites that might increase viral fitness during interhost transmission at the population level. PMID- 17719855 TI - Altered DNA repair and recombination responses in mouse cells expressing wildtype or mutant forms of RAD51. AB - Rad51, a homolog of Esherichia coli RecA, is a DNA-dependent ATPase that binds cooperatively to single-stranded DNA forming a nucleoprotein filament, which functions in the strand invasion step of homologous recombination. In this study, we examined DNA repair and recombination responses in mouse hybridoma cells stably expressing wildtype Rad51, or Walker box lysine variants, Rad51-K133A or Rad51-K133R, deficient in ATP binding and ATP hydrolysis, respectively. A unique feature is the recovery of stable transformants expressing Rad51-K133A. Augmentation of the endogenous pool of Rad51 by over-expression of transgene encoded wildtype Rad51 enhances cell growth and gene targeting, but has minimal effects on cell survival to DNA damage induced by ionizing radiation (IR) or mitomycin C (MMC). Whereas expression of Rad51-K133A impedes growth, in general, neither Rad51-K133A nor Rad51-K133R significantly affected survival to IR- or MMC induced damage, but did significantly reduce gene targeting. Expression of wildtype Rad51, Rad51-K133A or Rad51-K133R did not affect the frequency of intrachromosomal homologous recombination. However, in both gene targeting and intrachromosomal homologous recombination, wildtype and mutant Rad51 transgene expression altered the recombination mechanism: in gene targeting, wildtype Rad51 expression stimulates crossing over, while expression of Rad51-K133A or Rad51 K133R perturbs gene conversion; in intrachromosomal homologous recombination, cell lines expressing wildtype Rad51, Rad51-K133A or Rad51-K133R display increased deletion formation by intrachromosomal homologous recombination. The results suggest that ATP hydrolysis by Rad51 is more important for some homologous recombination functions than it is for other aspects of DNA repair. PMID- 17719856 TI - High prevalence of inducible clindamycin resistance among Staphylococcus aureus isolates from patients with cystic fibrosis. AB - BACKGROUND: Staphylococcus aureus (SA) is an important pathogen among patients with cystic fibrosis (CF). Inducible clindamycin resistance (ICR) has been described as a cause of treatment failure in non-CF related infections. The prevalence of ICR among SA from patients with CF is unknown. METHODS: We compared clindamycin susceptibilities of SA isolated from patients with and without cystic fibrosis (CF) using hospital microbiology data. Patients with CF were primarily identified using CF registry data. We evaluated all patients who had SA isolated at the Children's Healthcare of Atlanta microbiology laboratory during May 2004 May 2005. We performed antimicrobial susceptibility testing using broth microdilution and performed D-zone testing for ICR in accordance with the Clinical Laboratory Standards Institute (CLSI) document M100-S16. Proportions were compared using a 2-sided Pearson's Chi-square test or Fisher's exact test to assess for significance. RESULTS: Of 703 patients with methicillin-resistant SA (MRSA), 48% of CF patients (68/143) had at least one isolate demonstrating ICR, compared to 8% of non-CF patients (43/560) (P<0.01). Of 762 patients with methicillin-susceptible SA (MSSA), 29% of CF patients (73/254) had at least one isolate demonstrating ICR compared to 17% of non-CF patients (88/508) (P<0.01). CONCLUSIONS: SA demonstrating ICR are significantly more prevalent among patients with CF than among those without CF. PMID- 17719857 TI - Gender differences in treatment adherence among youth with cystic fibrosis: development of a new questionnaire. AB - BACKGROUND: Some prior studies have reported that girls with cystic fibrosis (CF) experience higher morbidity and mortality compared to boys. In this study, the authors compared boys' and girls' perceptions of disease-related strains and resources associated with living with CF, and the relationship of these factors to CF treatment feelings and behaviors. METHODS: All 10-21 year olds with CF at the Minnesota Cystic Fibrosis Center were invited by mail to complete a new self report survey (Living with CF Questionnaire--LCFQ). Of these 177 youth, 58% (49 boys and 54 girls) returned surveys. RESULTS: Exploratory and confirmatory factor analyses revealed nine factors in the LCFQ. Partial support was found for hypothesized gender differences in these factors. Compared to boys, girls reported significantly more illness-related strains and worries, including emotional strains, greater treatment discouragement, lower self-esteem, and lower adherence to some aspects of the CF treatment regimen (coughing, eating high-fat foods, taking meds/pills). CONCLUSIONS: Living with CF appears to have a greater emotional impact on adolescent girls compared to boys. These gender differences may contribute to the poorer pulmonary function observed among girls with cystic fibrosis during the adolescent years. PMID- 17719858 TI - An analytical method with a single extraction procedure and two separate high performance liquid chromatographic systems for the determination of artesunate, dihydroartemisinin and mefloquine in human plasma for application in clinical pharmacological studies of the drug combination. AB - The combination of two sensitive, selective and reproducible reversed phase liquid chromatographic (RP-HPLC) methods was developed for the determination of artesunate (AS), its active metabolite dihydroartemisinin (DHA) and mefloquine (MQ) in human plasma. Solid phase extraction (SPE) of the plasma samples was carried out on Supelclean LC-18 extraction cartridges. Chromatographic separation of AS, DHA and the internal standard, artemisinin (QHS) was obtained on a Hypersil C4 column with mobile phase consisting of acetonitrile-0.05 M acetic acid adjusted to pH 5.2 with 1.0M NaOH (42:58, v/v) at the flow rate of 1.50 ml/min. The analytes were detected using an electrochemical detector operating in the reductive mode. Chromatography of MQ and the internal standard, chlorpromazine hydrochloride (CPM) was carried out on an Inertsil C8-3 column using methanol-acetonitrile-0.05 M potassium dihydrogen phosphate adjusted to pH 3.9 with 0.5% orthophosphoric acid (50:8:42, v/v/v) at a flow rate of 1.00 ml/min with ultraviolet detection at 284 nm. The mean recoveries of AS and DHA over a concentration range of 30-750 ng/0.5 ml plasma and MQ over a concentration of 75 1500 ng/0.5 ml plasma were above 80% and the accuracy ranged from 91.1 to 103.5%. The within-day coefficients of variation were 1.0-1.4% for AS, 0.4-3.4% for DHA and 0.7-1.5% for MQ. The day-to-day coefficients of variation were 1.3-7.6%, 1.8 7.8% and 2.0-3.4%, respectively. Both the lower limit of quantifications for AS and DHA were at 10 ng/0.5 ml and the lower limit of quantification for MQ was at 25 ng/0.5 ml. The limit of detections were 4 ng/0.5 ml for AS and DHA and 15 ng/0.5 ml for MQ. The method was found to be suitable for use in clinical pharmacological studies. PMID- 17719859 TI - Medical options for treating perianal Crohn's disease. AB - Perianal Crohn's disease can cause significant morbidity for patients affected by the disease. However, diagnostic modalities and treatment options have progressed changing the goals of treatment from fistula "improvement" to complete cessation of drainage. Fistula closure and fibrosis of the fistula track is achieved in some patients. Furthermore, treatment has become a combined effort between medical physicians and surgeons. Simple disease can be treated with medical therapy alone consisting of antibiotics and immunomodulators. Infliximab should be added to refractory simple disease or simple disease with the presence of inflammation. If complex fistula disease is evident a surgical evaluation should also be done to determine if intervention is indicated. Complex disease should be treated with antibiotics, immunomodulators and biologic therapy from the onset. This review will summarise current data regarding medical options for treatment of fistulising Crohn's disease. PMID- 17719860 TI - Detection of anti-endomysial and anti-tissue transglutaminase autoantibodies in media following culture of oral biopsies from patients with untreated coeliac disease. AB - BACKGROUND AND AIMS: Coeliac disease is an autoimmune disorder characterised by high levels of anti-endomysial and anti-tissue transglutaminase autoantibodies in sera and media of cultured intestinal mucosa biopsies from affected patients. In this study, we wished to investigate whether anti-endomysial and anti-tissue transglutaminase antibodies can also be detected in culture media of oral mucosa specimens, and whether the mouth can be used as an area of immunological testing for coeliac disease. METHODS: Small intestine and cheek biopsy samples taken from 16 patients with active coeliac disease and from 11 controls were cultured in vitro for 48 h at 37 degrees C in presence of medium alone. Anti-endomysial and anti-tissue transglutaminase were detected in sera and in supernatants of these cultured biopsy samples by indirect immunofluorescence and enzyme immunoassay (EIA), respectively. RESULTS: Anti-endomysial and anti-tissue transglutaminase were positive in sera of 15/16 coeliac disease patients. Culture media of intestinal mucosa samples from 14/16 coeliac disease patients were anti endomysial positive, while the same antibodies were positive in supernatants of cultured oral mucosa samples from 15/16 coeliac disease patients. Anti-tissue transglutaminase were positive in both intestinal and oral culture media of 15/16 coeliac disease patients. Neither anti-endomysial nor anti-tissue transglutaminase were found in sera or in culture supernatants of both intestinal and oral biopsy samples from 11 controls. CONCLUSIONS: Our study suggests a new immunological site to detect the pathognomonic autoantibodies of coeliac disease and confirms that the mouth is involved in this illness. PMID- 17719861 TI - Neurological outcomes following preterm birth. AB - Neonatal survival continues to improve; for many years, including throughout the 1990s there have been anxieties that this was at the cost of additional morbidity, most particularly in terms of neurosensory impairments. Recent evidence suggests that rates of neuromotor morbidity, in particular cerebral palsy, may be declining for all but the most immature babies. Severe sensory impairment has a low, but relatively static incidence. High prevalence, low severity motor problems and their inter-relationship with developmental co ordination disorder, executive dysfunction and cognitive impairment are increasingly recognised and correlated with reduced school performance. Because of difficulties in comparing outcomes across different populations, validated motor and manual function classifications have been developed for children with cerebral palsy and can help to standardise outcome measures. Improved neuro imaging is helping us understand the types and consequences of neonatal brain injury. The possibility of using composite measures of early motor movement quality, longitudinal use of motor classification systems and volumetric magnetic resonance imaging (MRI) imaging to understand developmental processes needs to be explored. PMID- 17719862 TI - Simplifying soft tissue closure of the large meningomyelocele defect: a technical note. AB - The surgical management of large neural tube defects not amenable to primary closure poses a significant challenge. As a result, large residual skin defects often prompt excessively aggressive primary closure, complicated skin incisions, or flap advancements. However, our experience with the purse-string closure of a large meningomyelocele skin defect demonstrates that this technique can effectively provide coverage of very large meningomyelocele defects with minimal residual deformity. Here, we discuss the successful coverage of a large 5 x 5 cm meningomyelocele skin wound via staged purse-string closure spaced 2 weeks apart. PMID- 17719863 TI - Delayed transport of tissue-nonspecific alkaline phosphatase with missense mutations causing hypophosphatasia. AB - Hypophosphatasia is a rare genetic disease characterized by diminished bone and tooth mineralization due to deficient activity of tissue-nonspecific alkaline phosphatase (TNSALP). The disease is clinically heterogeneous due to different mutations in the TNSALP gene. In order to determine whether mutated TNSALP proteins may be sequestered, degraded, or subjected to delay in their transport to the cell membrane, we built a plasmid expressing a YFP-TNSALP fluorescent fusion protein allowing the observation of cellular localization in live cells by fluorescence confocal microscopy at different time points after transfection. We studied five mutants (c. 571G>A, c. 653T>C, c. 746G>T, c. 1363G>A and c. 1468A>T) exhibiting various levels of in vitro residual enzymatic activity. While the wild type protein reached the membrane within the first 24h after transfection, the mutants reached the membrane with delays of 24, 48 or 72 h. For all of the tested mutations, accumulation of the mutated proteins, mainly in the Golgi apparatus, was observed. We concluded that reduced ALP activity of these TNSALP mutants results from structural disturbances and delay in membrane anchoring, and not from compromised catalytic activity. PMID- 17719864 TI - DNA microarray analysis reveals a role for lysophosphatidic acid in the regulation of anti-inflammatory genes in MC3T3-E1 cells. AB - Lysophosphatidic acid (LPA) is a bioactive lipid with functional properties that overlap those of growth factors and cytokines. LPA production in vivo is linked to platelet degranulation and the biological activities of this lipid are associated with wound healing. Osteoblasts and their progenitor cells are exposed to high levels of this lipid factor in regions adjacent to bone fractures and we postulate a role for LPA in skeletal healing. The regeneration of bone injuries requires a complex array of changes in gene expression, but the effects of LPA on mRNA levels in bone cells have not been investigated. We performed a genome-wide expression analysis in LPA-treated MC3T3-E1 pre-osteoblastic cells using Affymetrix GeneChip arrays. Cells exposed to LPA for 6 h exhibited 513 regulated genes, whereas changes in the levels of 54 transcripts were detected after a 24-h LPA treatment. Gene ontology analysis linked LPA-regulated gene products to biological processes that are known to govern bone healing, including cell proliferation, response to stress, organ development, chemotaxis/motility, and response to stimuli. Among the gene products most highly up-regulated by LPA were transcripts encoding the anti-inflammatory proteins sST2, ST2L, and heat-shock protein 25 (HSP25). RT-PCR analysis confirmed that these mRNAs were increased significantly in MC3T3-E1 cells and primary osteoblasts exposed to LPA. The response of cells to LPA is mediated by G-protein-coupled receptors, and the stimulation of anti-inflammatory gene expression in MC3T3-E1 cells was blocked by Ki16425, an inhibitor of LPA(1) and LPA(3) receptor forms. Pertussis toxin impaired only the LPA-induced expression of sST2. LPA-stimulated levels of sST2, ST2L and HSP25 mRNAs persisted if the cytosolic Ca(2+) elevations elicited by this lipid were blocked with BAPTA. In contrast to the stimulatory effect of LPA, exposure of MC3T3-E1 cells to fluid shear reduced the transcript levels of all three anti-inflammatory genes. The induction of sST2, ST2L and HSP25 expression by LPA suggests a role for this lipid factor in the regulation of osteoblastic cell function during periods of inflammation. PMID- 17719891 TI - Synthesis and electrochemical applications of gold nanoparticles. AB - This review covers recent advances in synthesis and electrochemical applications of gold nanoparticles (AuNPs). Described approaches include the synthesis of AuNPs via designing and choosing new protecting ligands; and applications in electrochemistry of AuNPs including AuNPs-based bioelectrochemical sensors, such as direct electrochemistry of redox-proteins, genosensors and immunosensors, and AuNPs as enhancing platform for electrocatalysis and electrochemical sensors. PMID- 17719892 TI - Advances in hyphenated analytical techniques for shotgun proteome and peptidome analysis--a review. AB - Proteomics is defined as the analysis of part or all of the protein components of a complex biological system (a cell, organ or tissue) at a given moment. Due to the huge number of proteins encoded by the genome, novel analytical techniques must be developed to meet the need of large scale analysis. This has led to the hyphenation of multiple techniques to achieve this object. Here current status of the hyphenated analytical techniques of one-dimensional and multidimensional liquid chromatography-mass spectrometry for shotgun proteomic analysis is reviewed, and on-line techniques for automated sample preparation and injection are also covered. In addition, the hyphenated techniques for peptidome analysis are also covered. PMID- 17719893 TI - Determination of trace alpha-fetoprotein variant by affinity adsorption solid substrate-room temperature phosphorimetry and its application to the forecast of human diseases. AB - In the presence of ion perturber LiAc, 4-generation polyamidoamine dendrimers (4G D) could emit strong and stable room temperature phosphorescence (RTP) signal at lambda(max)(ex)/lambda(max)(em) = 511.8/675.3 nm on nitrocellulose membrane (NCM), and Triton X-100 could sharply enhance the RTP signal of 4G-D. Triton X 100-4G-D was used to label concanavalin agglutinin (Con A) to get the labeling product Triton X-100-4G-D-Con A. Quantitative specific affinity adsorption (AA) reaction between Triton X-100-4G-D-Con A and alpha-fetoprotein variant (AFP-V) could be carried out on the surface of NCM, whose product Triton X-100-4G-D-Con A AFP-V could emit strong and stable RTP and its deltaI(p) was proportional to the content of AFP-V. According to the facts above, a new affinity adsorption solid substrate-room temperature phosphorimetry (AA-SS-RTP) for the determination of trace AFP-V by Con A labeled with Triton X-100-4G-D was established. Detection limits of this method were 0.23 fg spot(-1) (direct method, corresponding concentration: 5.8x10(-13) g mL(-1)) and 0.13 fg spot(-1) (sandwich method, corresponding concentration: 3.2x10(-13) g mL(-1)). It has been successfully applied to determine the content of AFP-V in human serum and forecast human diseases, for its high sensitivity, long RTP lifetime, good repeatability, high accuracy and little background perturbation with lambda(max)(em) at the long wavelength area. Meanwhile, the mechanism for the determination of trace AFP-V using AA-SS-RTP was also discussed. PMID- 17719894 TI - Volatilization of in situ generated antimony trichloride using aqua regia vapors for the determination of ultra trace impurities in high-purity antimony using inductively coupled plasma-mass spectrometry. AB - Volatilization of Sb has been carried out using vapors generated from aqua regia for the determination of non-volatile impurities present in antimony. The antimony trichloride (SbCl3) thus generated was volatilized >99.9% at 250 degrees C in 90 min. Recoveries of spiked impurities Al, Mn, Co, Ni, Cu, Sr, Ag, Cd, Ba, Pb were found to be >90% (47% for Pb) after volatilization of the matrix element. The only reagent used (aqua regia vapors) was generated in situ in a closed environment minimizing the external contamination. The procedure offers experimental blanks and method detection limits at lower ng g(-1) using ICP-MS. The method has been applied for the determination of impurities in two Sb samples of 99.5 and 99.999% (5N) purity. The developed method was validated using bromide volatilization procedure. The results obtained by the present method were also compared with those of Sector Field ICP-MS (SF-ICP-MS). PMID- 17719895 TI - Using mean field approach independent component analysis to fatty acid characterization with overlapped GC-MS signals. AB - In this paper, mean field independent component analysis (MF-ICA) was applied as a deconvolution method to separate complex gas chromatographic-mass spectrometric (GC-MS) signals obtained from fatty acid analysis of fish oil. The separation which is a blind operation was used as a complementary method in identification of the unknown components of a mixture and in quantification purposes, as well. In MF-ICA, the sources (mass spectra) are recovered from the mean of their posterior distributions and mixing matrix (chromatograms) and noise level are estimated through the maximum a posterior (MAP) solution. The number of independent components (ICs) in the overlapping signals can be estimated by the difference between the reconstructed and original GC-MS data. It was found that the chromatographic profiles and the mass spectra of the components in overlapping multicomponent GC-MS data can be accurately recovered with and without previously background correction. The resolved mass spectral sources satisfactory are identified using mass spectral search system. The recovered chromatographic area and the relative content of each analyte considering selected number of ICs are calculated and the results are compared with the ones obtained previously by using heuristic evolving latent projections (HELP) method. PMID- 17719896 TI - The performance of nu-support vector regression on determination of soluble solids content of apple by acousto-optic tunable filter near-infrared spectroscopy. AB - The nu-support vector regression (nu-SVR) was used to construct the calibration model between soluble solids content (SSC) of apples and acousto-optic tunable filter near-infrared (AOTF-NIR) spectra. The performance of nu-SVR was compared with the partial least square regression (PLSR) and the back-propagation artificial neural networks (BP-ANN). The influence of SVR parameters on the predictive ability of model was investigated. The results indicated that the parameter nu had a rather wide optimal area (between 0.35 and 1 for the apple data). Therefore, we could determine the value of nu beforehand and focus on the selection of other SVR parameters. For analyzing SSC of apple, nu-SVR was superior to PLSR and BP-ANN, especially in the case of fewer samples and treating the noise polluted spectra. Proper spectra pretreatment methods, such as scaling, mean center, standard normal variate (SNV) and the wavelength selection methods (stepwise multiple linear regression and genetic algorithm with PLS as its objective function), could improve the quality of nu-SVR model greatly. PMID- 17719897 TI - Dissolved iron analysis in estuarine and coastal waters by using a modified adsorptive stripping chronopotentiometric (SCP) method. AB - An electrochemical method based on adsorptive stripping chronopotentiometry (SCP) with a rotating mercury film electrode has been developed for the determination of dissolved iron (III) at subnanomolar concentrations in estuarine and coastal waters. The detection limit was 0.11 nM after adsorption time of 60s. Compared to the other chronopotentiometric methods available for dissolved iron measurement in natural and estuarine waters, the procedure described here exhibits a 15-fold better sensitivity. Therefore, it allows one to accurately quantify concentrations commonly found in estuarine and coastal waters. Moreover, by using the speciation scheme proposed by Aldrich and van den Berg (Electroanalysis 10 (1998) 369), several forms could be measured, i.e. reactive iron (Fe R) and reactive iron (III) (Fe(III) R), or estimated, i.e. complexed iron (Fe C) and reactive iron (II) (Fe(II) R). The method described here is reliable, fast, inexpensive and compact. It was applied successfully to the study of the chemical speciation of dissolved iron along the salinity gradient of the Aulne estuary (Brittany-France). PMID- 17719899 TI - A simple and rapid method for measuring dissolved oxygen in waters with gold microelectrode. AB - Dissolved oxygen (DO) is an essential indicator in chemical, biological and biochemical processes and needs to be rapidly measured in many cases. In this work, a rapid, sensitive and simple electrochemical method, first derivative linear sweep voltammetry (FD-LSV), was established for the determination of DO. The peak height of FD-LSV was found to be influenced by scan rate and microelectrode surface area. An empirical formula was proposed to describe the relationship between the FD-LSV peak height and the influencing factors. Compared with other electrochemical methods for DO determination, the FD-LSV method needed lesser time and was more accurate. This method was successfully applied for the determination of the DO levels of various environmental water samples. PMID- 17719898 TI - Detection of thrombin using electrogenerated chemiluminescence based on Ru(bpy)3(2+)-doped silica nanoparticle aptasensor via target protein-induced strand displacement. AB - A sensitive and selective aptasensor using tri(2,2'-bipyridyl)ruthenium(II)-doped silica nanoparticles (Ru(bpy)3(2+)-doped SNPs) as DNA tags for detection of thrombin is developed based on the target protein-induced strand displacement of the DNA probe. For the proposed aptasensor, the aptamer was assembled on the surface of the Au electrode through Au-S binding. The hybridization event between the DNA probe labeled by the Ru(bpy)3(2+)-doped SNPs and the aptamer was evaluated by electrogenerated chemiluminescence (ECL) measurements. Then, the DNA probe was displaced by thrombin and the binding event between the thrombin and the aptamer was monitored by ECL measurements again. The difference of ECL intensity (deltaI(ECL)) of the two events could be used to quantify the thrombin. Other proteins, such as bovine serum albumin and bovine hemoglobin, had almost negligible deltaI(ECL). Under the optimal conditions, the deltaI(ECL) was linearly related to the concentration of the thrombin in the range of 10 fM to 10 pM and the detection limit was down to 1.0 fM since SNPs containing a large number of Ru(bpy)3(2+) molecules were labeled on the DNA probe. PMID- 17719900 TI - Application of NiTi alloy coated with ZrO2 as a new fiber for solid-phase microextraction for determination of halophenols in water samples. AB - A new fiber for solid-phase microextraction (SPME) employing a metallic support coated with an inorganic material is proposed. A nitinol alloy (NiTi) was used as the support material due to its super elasticity and shape memory properties. Zirconium oxide (ZrO2) was electrodeposited onto NiTi using chronoamperometry. The surface characteristics and morphology of the coated and uncoated support were evaluated through scanning electronic microscopy and dispersive energy microanalysis. This assembly was applied in the extraction of three halophenols from aqueous samples. A multivariate approach was used for optimization of the variables involved in the system. The Doehlert matrix was used for evaluation of the best derivatization conditions and a Box-Behnken design to obtain the best extraction conditions. In order to investigate the repeatability, one fiber was used for six extraction tests under similar conditions and the relative standard deviations (R.S.D.) were lower than 12.5%. Detection limits were lower than 0.30 ng mL(-1). Correlation coefficients were higher than 0.997. Extraction efficiency of the NiTi-ZrO2 fiber was similar to a PDMS 7 microm commercial fiber, even though it had a lower coating thickness of 1.35 microm. Considering the amount extracted per unit volume, the NiTi-ZrO2 fiber had a better extraction profile when compared to commercial fibers. The new SPME fiber has a lifetime of over 500 extractions. Thus, it is a promising alternative for low-cost analysis, as the proposed fiber is robust, and easily and inexpensively prepared. PMID- 17719901 TI - Evaluation of carbohydrate antigen 50 in human serum using magnetic particle based chemiluminescence enzyme immunoassay. AB - A magnetic particles (MPs)-based chemiluminescence enzyme immunoassay (CLEIA) with high sensitivity, specificity, rapidity, and reproducibility was proposed for the evaluation of tumor marker, carbohydrate antigen 50 (CA50) in human serum. The immunomagnetic particles coated with anti-fluorescein isothiocyanate (FITC) antibody was used as dispersed solid phase for the immunoassay, which was based on a sandwich immunoreaction of FITC-labeled anti-CA50 antibody, CA50 antigen, and alkaline phosphatase (ALP)-labeled anti-CA50 antibody, and was based on a subsequent chemiluminescence reaction of ALP with 4-methoxy-4-(3-phosphate phenyl)-spiro-(1,2-dioxetane-3,2'-adamantane) (AMPPD) solution. The CL emission intensity was directly proportional to the amount of analyte present in a sample solution. The effects of several physicochemical parameters, including the concentration of FITC-labeled anti-CA50 antibody, the dilution ratio of ALP labeled anti-CA50 antibody, the volume of MPs and substrate, the immunoreaction time and other relevant variables upon the immunoassay were studied and optimized. The proposed method exhibited advantages in a lower minimum detectable concentration of 1.0 U mL(-1) with comparison to the commercially available immunoradiometric assay (IRMA), and showed a larger linear range of 0 to 300 U mL(-1), as well as less total assay time of only 50 min with comparison to both IRMA and microplate CLEIA. The coefficient of variation was less than 7 and 11% for intra- and inter-assay precision, respectively. This method has been successfully applied to the evaluation of CA50 in human serum with recoveries from 82 to 112%, and showed a good correlation with the commercially available CA50 IRMA. PMID- 17719902 TI - Differentiation of isomeric allylic alkenyl methyl ethers by Raman spectroscopy. AB - The Raman spectra of several pairs of alkenyl methyl ethers of general structure R(1)R(2)C=CR(5)C(R(3)R(4))OCH3 and R(1)R(2)C(OCH3)C(R(5))=CR(3)R(4) (R(1), R(2), R(3), R(4), R(5) = H or C(n)H(2n+1), n = 1-3) are reported and discussed, with a view to establishing whether Raman spectroscopy offers a viable means of distinguishing between these isomeric unsaturated species. Key bands associated with the nu(sp2C-H) and nu(C=C) stretching modes are found to be particularly useful in this connection: R(1)R(2)C=CHCH2OCH3 and R(1)R(2)C(OCH3)CH=CH2 ethers (R(1), R(2) = CH3, C2H5) are easily distinguished on this basis. Differentiation of their lower homologues, R(1)CH=CHCH2OCH3 and R(1)CH(OCH3)CH=CH2 (R(1) = CH3, C2H5, C3H7), by similar means is also quite straightforward, even in cases where cis and trans isomers are possible. Pairs of isomeric ethers, such as CH3CH=C(CH3)CH2OCH3 and CH3CH(OCH3)C(CH3)=CH2, in which the structural differences are more subtle, may also be distinguished with care. Deductions based on bands ascribed to the stretching vibrations are usually confirmed by consideration of the signals associated with the corresponding delta(sp2C-H) deformation vibrations. Even C2H5CH=CHCH(C3H7)OCH3 and C3H7CH=CHCH(C2H5)OCH3 are found to have distinctive Raman spectra, but differentiation of these closely related isomers requires additional consideration of the low wavenumber region. PMID- 17719903 TI - Direct, non-destructive quantitative measurement of an active pharmaceutical ingredient in an intact capsule formulation using Raman spectroscopy. AB - The active pharmaceutical ingredient (ambroxol) in an intact capsule formulation has been non-destructively quantified using Raman spectroscopy. To improve the problem of insufficient representative sampling inherent in Raman measurements, we have employed a wide area illumination (WAI) scheme that enables much improved sample coverage through a circular excitation laser spot with a 6 mm diameter. One of the anticipated sources of variation for this measurement was variation in the capsule shells. However, the WAI scheme significantly decreased the spectral variation among empty capsules compared to a measurement with a traditional small spot excitation. Therefore, measurement variations emanating from the capsule shell did not significantly influence the accuracy of the determination of ambroxol concentrations. The resulting standard error of prediction (SEP) using the WAI scheme was comparable to that from previous Raman measurements which used a conventional small-spot excitation and employed a sampling scheme that involved rotation of an ambroxol pellet. It is further noteworthy that the SEP was also similar to that obtained from the use of transmission NIR spectroscopy, which was achieved by collection of spectra of the powdered capsule contents removed from the shell. The proposed Raman measurement using the WAI scheme in this case was sufficient to achieve the quantitative measurement of the active pharmaceutical ingredient (API) content of capsules non-destructively. PMID- 17719904 TI - An integrated portable hand-held analyser for real-time isothermal nucleic acid amplification. AB - A compact hand-held heated fluorometric instrument for performing real-time isothermal nucleic acid amplification and detection is described. The optoelectronic instrument combines a Printed Circuit Board/Micro Electro Mechanical Systems (PCB/MEMS) reaction detection/chamber containing an integrated resistive heater with attached miniature LED light source and photo-detector and a disposable glass waveguide capillary to enable a mini-fluorometer. The fluorometer is fabricated and assembled in planar geometry, rolled into a tubular format and packaged with custom control electronics to form the hand-held reactor. Positive or negative results for each reaction are displayed to the user using an LED interface. Reaction data is stored in FLASH memory for retrieval via an in-built USB connection. Operating on one disposable 3 V lithium battery >12, 60 min reactions can be performed. Maximum dimensions of the system are 150 mm (h) x 48 mm (d) x 40 mm (w), the total instrument weight (with battery) is 140 g. The system produces comparable results to laboratory instrumentation when performing a real-time nucleic acid sequence-based amplification (NASBA) reaction, and also displayed comparable precision, accuracy and resolution to laboratory-based real-time nucleic acid amplification instrumentation. A good linear response (R2 = 0.948) to fluorescein gradients ranging from 0.5 to 10 microM was also obtained from the instrument indicating that it may be utilized for other fluorometric assays. This instrument enables an inexpensive, compact approach to in-field genetic screening, providing results comparable to laboratory equipment with rapid user feedback as to the status of the reaction. PMID- 17719905 TI - Optical fluoride sensor based on monomer-dimer equilibrium of scandium(III) octaethylporphyrin in a plasticized polymeric film. AB - A fluoride-selective optical sensor based on scandium(III)-octaethylporphyrin (Sc(III)OEP) as an ionophore within a plasticized PVC film is described. The presence of fluoride ion in the aqueous sample phase increases the formation of a difluoro-bridged Sc(III)OEP dimer species in the polymer film. The ability of the Sc(III) porphyrin to form the dimeric structure in the presence of fluoride is confirmed by UV-vis spectroscopy and X-ray crystallography. For more practical sensing applications, a pH chromoionophore (ETH 7075) is added to the plasticized PVC film along with Sc(III)OEP and the observed optical response is based on coextraction of protons with sample phase fluoride to create the dimeric porphyrin and a protonated chromoionophore species. The selectivity pattern observed is F- >> ClO4(-), SCN-, NO3(-) > Br-, Cl-. Only organic salicylate is a significant interferent. Fast and reversible fluoride response is observed over the range of 10(-4) to 10(-2) M fluoride, allowing use of the sensing film in a waveguide configuration for flow-injection measurements. PMID- 17719906 TI - Resonance Rayleigh scattering spectral method for the determination of raloxifene using gold nanoparticle as a probe. AB - When gold nanoparticles were being prepared by sodium citrate reduction method, citrate anions self-assembled on the surface of gold nanoparticles to form supermolecular complex anions with negative charges, and protonated raloxifene (Ralo) was positively charged and could bind with the complex anions to form larger aggregates through electrostatic force and hydrophobic effects, which could result in the remarkable enhancement of the resonance Rayleigh scattering intensity (RRS), and the appearance of new RRS spectra. At the same time, the second-order scattering (SOS) and frequency-doubling scattering (FDS) intensities were also enhanced. The maximum wavelengths were located near 370 nm for RRS, 520 nm for SOS, and 350 nm for FDS, respectively. Among them, the RRS method had the highest sensitivity and the detection limit was 5.60 ng mL(-1) for Ralo, and its linear range was 0.05-2.37 microg mL(-1). A new RRS method for the determination of trace Ralo using gold nanoparticles probe was developed. The optimum conditions of the reaction and influencing factors were investigated. In addition, the reaction mechanism and the reasons for the enhancement of RRS were discussed. PMID- 17719907 TI - Stability-indicating high performance thin layer chromatography determination of Paroxetine hydrochloride in bulk drug and pharmaceutical formulations. AB - A simple selective precise and stability-indicating high performance thin layer chromatographic method of analysis of Paroxetine hydrochloride both as a bulk drug and in formulations was developed and validated. The method employed TLC (Thin Layer Chromatography) aluminum precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of butanol:acetic acid:water (8:2:0.5, v/v/v). This system was found to give compact spots for Paroxetine HCl (Rf, retardation factor, value-0.48+/-0.02). Paroxteine HCl was subjected to acid and alkali hydrolysis, oxidation and photodegradation, where the degraded product was well separated from the pure drug. Densitometric analysis of Paroxetine hydrochloride was carried out in the absorbance mode at 295 nm. The linear regression analysis data for the calibration spots showed good relationship with (regression) r2 = 0.9903 in the amount range of 300-1500 ng (nanogram) per spot. The mean value of co-relation co-efficient, slope and intercept were 0.9903+/ 0.001, 5.38+/-0.058 and 182.5+/-2.16 respectively. The method was validated for precision, recovery and robustness. The limits of detection and quantitation were 50 and 150 ng, respectively. The drug does not undergo degradation with oxidation, but gets affected in acidic and alkaline conditions. The acid and alkali degradation showed extra peaks at 0.4 and 0.08 Rf, respectively. This indicates that the drug is susceptible to acidic and alkaline medium. As the method could effectively separate the drug from its degradation products, it can be employed as a stability-indicating one. PMID- 17719908 TI - Competing ligand exchange-solid phase extraction method for the determination of the complexation of dissolved inorganic mercury (II) in natural waters. AB - A method employing dual competitive ligand exchange followed by solid phase extraction (CLE-SPE) for characterizing the complexation of inorganic Hg(II) in natural waters is described. This method employs parallel use of two competing ligands: diethyldithiolcarbamate (DEDC), which forms hydrophobic complexes with Hg(II), and thiosalicylic acid (TSA), which forms hydrophilic complexes with Hg(II). Inorganic mercury complexed by natural and competing ligands are separated based on hydrophobicity using C18 solid phase extraction columns. Data modeling allows for the calculation of the concentration and conditional stability constants of natural ligands capable of complexing Hg(II) in both the operationally defined hydrophilic and hydrophobic fractions. The use of multiple ligand concentrations, and thus multiple analytical windows, to characterize different ligand classes within both of these two fractions is described. Studies of the kinetics of the ligand exchange involved, potential for changes in the stability of natural ligands during freezing and thawing, potential breakthrough during solid phase extraction, as well as the method's precision and estimation of error, are presented and discussed. Results from the application of the method to natural freshwaters demonstrated that in the limited samples collected over 99.99% of the ambient inorganic mercury is strongly complexed by ligands with conditional stability constants (K(HgL)(cond), Hg2+) on the order of 10(30), values similar to that of reduced sulfur ligands. At ambient conditions 85-90% of the mercury exists in hydrophobic complexes in these freshwaters, but strong Hg binding ligands exist in both the hydrophobic and hydrophilic fractions. PMID- 17719909 TI - Depressed neuroplasticity in major depressive disorder? PMID- 17719918 TI - The natural history of thyroid autoimmunity and thyroid function in children with type 1 diabetes. PMID- 17719919 TI - Transfusion threshold in anemic premature infants. PMID- 17719922 TI - Extreme obesity among children in Mexico. PMID- 17719923 TI - American pediatric academia: the looming question. PMID- 17719924 TI - Are patients with Kawasaki disease at risk for premature atherosclerosis? PMID- 17719925 TI - Non! to non-steroidal anti-inflammatory therapy for inflammatory lung disease in cystic fibrosis (at least at the moment). PMID- 17719926 TI - What is the role of cystic fibrosis transmembrane conductance regulator dysfunction in primary sclerosing cholangitis? PMID- 17719927 TI - Specific immune globulin therapy for prevention of nosocomial staphylococcal bloodstream infection in premature infants: not what we hoped for! PMID- 17719928 TI - Acute viral bronchiolitis: to treat or not to treat-that is the question. PMID- 17719929 TI - "And things that go bump in the night": nothing to fear? PMID- 17719930 TI - Subclinical atherosclerosis, but normal autonomic function after Kawasaki disease. AB - OBJECTIVE: To compare the carotid artery intima-media-thickness (IMT) of children with Kawasaki disease with normative data for Western children. STUDY DESIGN: Forty-eight children (20 patients after Kawasaki disease, mean age 12.1 +/- 4.7 years; 28 age- and sex-matched healthy controls, mean age 12.0 +/- 3.1 years) were studied. RESULTS: Mean (IMT differed significantly (0.449 +/- 0.02 vs 0.424 +/- 0.01, P < .001) as well as IMT standard deviation score (1.2 +/- 0.6 vs 0.3 +/- 0.1, P < .001). Patients with coronary arterial involvement (n = 15) showed a further increase of the IMT (0.459 +/- 0.01 vs 0.436 +/- 0.01, P < .05). There was no difference regarding short-term blood pressure regulation. CONCLUSIONS: In this small patient group, signs of subclinical atherosclerosis after Kawasaki disease have been detected. These preliminary data indicate that these patients may be at risk for cardiovascular disease even in the absence of permanent alterations of the coronary arteries. PMID- 17719931 TI - Are patients after Kawasaki disease at increased risk for accelerated atherosclerosis? AB - OBJECTIVE: To assess whether patients after Kawasaki disease (KD) have increased risk factors and abnormalities suggestive of early atherosclerosis in systemic arteries. STUDY DESIGN: In a case-control study, we compared 52 patients after typical Kawasaki disease with varying coronary artery involvement (67% males; mean time from illness episode 11.2 +/- 3.7 years) studied between 10 and 20 years of age with 60 healthy control subjects (50% males). Brachial artery reactivity (BAR) was assessed using vascular ultrasonography, and atherosclerosis risk assessment was performed. Differences between cases and controls and factors associated with endothelial function in cases were determined. RESULTS: Case patients had lower resting systolic blood pressure (P < .001), lower apolipoprotein AI levels (P < .05), and higher levels of glycosylated hemoglobin (P = .007). There were no significant differences in BAR between case patients and control subjects in response to increased flow (P = .60) and nitroglycerine (P = .93). For case patients, significant factors in multivariable analysis for lower flow-mediated BAR included higher fasting triglyceride levels (P = .04) and lower free fatty acid levels (P < .001). No significant relationship was noted with past or current coronary artery involvement. CONCLUSION: Patients with KD have some abnormalities for risk factors for atherosclerosis, but systemic arterial endothelial dysfunction is not present in the long term. PMID- 17719932 TI - High-dose ibuprofen in cystic fibrosis: Canadian safety and effectiveness trial. AB - OBJECTIVE: To assess the effectiveness and safety of high-dose ibuprofen when used as part of routine therapy in patients with cystic fibrosis (CF). STUDY DESIGN: In this multicenter, double-blinded, placebo-controlled trial, a total of 142 patients age 6 to 18 years with mild lung disease (forced expiratory volume in 1 minute [FEV1] > 60 predicted) were randomized to receive either high-dose ibuprofen (70 subjects, 20 to 30 mg/kg/twice daily, adjusted to a peak serum concentration of 50 to 100 mug/mL) or placebo (72 subjects) for a 2-year period. The primary outcome was the annualized rate of change in FEV1% predicted. RESULTS: The patients in the high-dose ibuprofen group exhibited a significant reduction in the rate of decline of forced vital capacity percent predicted (0.07 +/- 0.51 vs -1.62 +/- 0.52; P = .03), but not FEV1%. The ibuprofen group also spent fewer days in hospital after adjusting for age (1.8 vs 4.1 days per year; P = .07). A total of 11 patients (4 in the ibuprofen group and 7 in the placebo group) withdrew due to adverse events. CONCLUSIONS: High-dose ibuprofen has a significant effect on slowing the progression of lung disease in CF and generally is well tolerated. PMID- 17719933 TI - Primary sclerosing cholangitis in childhood is associated with abnormalities in cystic fibrosis-mediated chloride channel function. AB - OBJECTIVE: To determine whether primary sclerosing cholangitis (PSC) in childhood is associated with abnormalities in cystic fibrosis transmembrane conductance regulator (CFTR). STUDY DESIGN: Subjects with PSC diagnosed in childhood (n = 20) were recruited from Children's Hospital. Subjects had testing with sweat chloride concentration, nasal transmembrane potential difference, and extensive genetic analysis of the CFTR gene. Disease control subjects consisted of 14 patients with inflammatory bowel disease alone and no liver disease. t tests were performed to determine statistical significance. RESULTS: In the PSC group, CFTR chloride channel function (deltaChloride free + isoproterenol) was markedly diminished at 8.6 +/- 8.2 mV (reference range: -24.6 +/- 10.4 mV). In contrast, disease control subjects had normal function, at -17.8 +/- 9.7 mV (P = .008). Sweat chloride concentration in subjects with PSC was greater than in disease control subjects (20.8 +/- 3.4 mmol/L vs 12.0 +/- 1.6 mmol/L, P = .045). Comprehensive CFTR genotyping revealed that 5 of 19 (26.3%) subjects with PSC had a CFTR mutation or variant, compared with 6 of 14 (42.9%) disease control subjects. CONCLUSIONS: There is a high prevalence of CFTR-mediated ion transport dysfunction in subjects with childhood PSC. PMID- 17719934 TI - Clinical trial of safety and efficacy of INH-A21 for the prevention of nosocomial staphylococcal bloodstream infection in premature infants. AB - OBJECTIVE: To determine if INH-A21, an intravenous immune globulin (IGIV) derived from donors with high titers of antibody to surface adhesins of Staphylococcus epidermidis and S. aureus prevents late-onset sepsis (LOS) in very low birth weight (VLBW) infants. STUDY DESIGN: In this double-blind, placebo-controlled study, infants with birth weights 500 to 1250 g were randomized to receive up to four doses of INH-A21 (Veronate) or placebo. The primary objective was to determine the safety and efficacy of INH-A21 versus placebo for prevention of S. aureus LOS in VLBW infants. RESULTS: A total of 1983 infants from 95 neonatal intensive care units were randomized, and received at least one dose of study drug. S. aureus LOS developed in 50 of 989 (5%) and 60 of 994 (6%) infants who received placebo or INH-A21, respectively (P = .34). No differences were found in the frequencies of LOS caused by coagulase-negative staphylococci (CoNS), Candida spp, or overall mortality. No adverse events were statistically significantly associated with INH-A21 infusions compared with placebo. CONCLUSION: INH-A21 failed to reduce the incidence of staphylococcal LOS or candidemia in premature infants. PMID- 17719935 TI - Nebulized hypertonic saline in the treatment of viral bronchiolitis in infants. AB - OBJECTIVE: To investigate the use of nebulized 3% hypertonic saline (HS) for treating viral bronchiolitis in moderately ill hospitalized infants by a prospective, randomized, double-blinded, controlled, multicenter trial. STUDY DESIGN: A total of 96 infants (mean age, 4.7 months; range, 0.3 to 18 months) admitted to the hospital for treatment of viral bronchiolitis were recruited from 3 regional pediatric centers over 3 bronchiolitis seasons (December 2003 to May 2006). Patients were randomized to receive, in a double-blind fashion, repeated doses of nebulized 3% HS (treatment group) or 0.9% normal saline (NS; control group), in addition to routine therapy ordered by the attending physician. The principal outcome measure was hospital length of stay (LOS). RESULTS: On an intention-to-treat basis, the infants in the HS group had a clinically relevant 26% reduction in LOS to 2.6 +/- 1.9 days, compared with 3.5 +/- 2.9 days in the NS group (P = .05). The treatment was well tolerated, with no adverse effects attributable to the use of HS. CONCLUSIONS: The use of nebulized 3% HS is a safe, inexpensive, and effective treatment for infants hospitalized with moderately severe viral bronchiolitis. PMID- 17719936 TI - Deaths and injuries attributed to infant crib bumper pads. AB - OBJECTIVE: To document deaths attributed to bumper pads and injuries from their use that are potentially preventable. STUDY DESIGN: The US Consumer Product Safety Commission maintains files on cases voluntarily reported to them of deaths and injury related to commercial products. These cases represent an unknown fraction of total occurrences. We searched this database for deaths related to crib bumpers for the years 1985 to 2005. We also searched other Consumer Product Safety Commission databases for crib-related injuries that potentially might have been prevented by bumpers. Additionally, we examined 22 retail crib bumpers and described features that could be hazardous. RESULTS: Twenty-seven accidental deaths reported by medical examiners or coroners were attributed to bumper pads. The mechanism of death included suffocation and strangulation by bumper ties. Twenty-five nonfatal injuries were identified, and most consisted of minor contusions. All retail bumpers had hazardous properties. CONCLUSIONS: These findings suggest that crib and bassinet bumpers are dangerous. Their use prevents only minor injuries. Because bumpers can cause death, we conclude that they should not be used. PMID- 17719937 TI - Insulin resistance in adolescents. AB - OBJECTIVES: To investigate the relationship of other body mass index (BMI) ranges with Homeostasis Model Assessment-Insulin Resistance (HOMA-IR), a surrogate marker for insulin resistance in adolescents. STUDY DESIGN: Cross-sectional analysis of a nationally representative sample of 1837 nondiabetic, nonpregnant 12 to 19 year old persons from the National Health and Nutrition Examination Survey, 1999-2002. The main outcome measurement of insulin resistance was calculated as HOMA-IR > 3.16. RESULTS: Having a BMI > or = 75th percentile is associated with a high HOMA-IR levels. As the BMI percentile increases, the odds of high HOMA-IR levels increase (BMI percentile 75-84.9, OR 4.277, 95% CI 2.090 8.752; BMI percentile 85-94.9, OR 4.299, 95% CI 2.158-8.563; BMI > or = 95th percentile, OR 17.907, 95% CI 11.360-28.228). CONCLUSION: Adolescents with BMI percentile of 75 to 84.9, which represents approximately 1.2 million US adolescents, have not previously been identified as having higher HOMA-IR levels. PMID- 17719938 TI - A cognitive behavioral therapy program for overweight children. AB - OBJECTIVE: To assess the 1-year results of a multidisciplinary, cognitive behavioral therapy treatment program for overweight and obese children. STUDY DESIGN: Children (n = 73; 8 to 15 years old) participated in a prospective study aimed at reduction of the body mass index-standard deviation score (BMI-SDS), adapting a healthy lifestyle and creating a positive self-image and higher self esteem, by use of a group approach and parental involvement. Reduction in BMI-SDS and percent overweight were measured and analyzed by use of MIXED modeling. RESULTS: The participants achieved a 0.6 BMI-SDS reduction, comparable to a weight loss of 18.7% after 1 year (P < .0001). The proportion of dropouts was 33%. Compared with the follow-up group, dropouts were older, increased in BMI-SDS before start of treatment, and were less successful in BMI-SDS reduction during treatment. CONCLUSIONS: This treatment program had a positive effect on BMI-SDS in overweight and obese children at 1-year follow-up. Differences between the characteristics of the dropout and follow-up group may reflect predictor variables for treatment outcome. PMID- 17719939 TI - Socioeconomic position, maternal IQ, home environment, and cognitive development. AB - OBJECTIVE: To assess whether socioeconomic position, maternal intelligence (IQ), and the home environment are inter-related to cognitive development in childhood. STUDY DESIGN: Prospective cohort study (n = 723) with cognitive tests at ages 2, 4, 7, and 11 to 13 years. RESULTS: There were statistically significant positive associations of father's occupational prestige, Home Observation for Measurement of Environment (HOME) score, and maternal IQ with cognitive performance in childhood. After adjustment for confounding factors, there was an increase in cognitive development by 0.8 to 2.0, 2.9 to 4.8, and 4.2 to 9.0 points for a 10 unit increment in father's occupational prestige, maternal IQ, and HOME score, respectively. CONCLUSIONS: These results demonstrate that socioeconomic position, maternal IQ, and the home environment are independently and positively predictive of children's cognitive development. These findings provide additional rationale for implementing social policies that reduce socioeconomic inequalities. PMID- 17719940 TI - A randomized, controlled trial of tonsillectomy in periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome. AB - OBJECTIVE: We carried out a prospective, randomized, controlled trial to clarify the effect of tonsillectomy on the clinical course of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. STUDY DESIGN: Twenty-six consecutive children (mean age 4.1 years) with at least 5 PFAPA attacks were recruited from 3 tertiary care pediatric hospitals during 1999-2003 and randomly allocated to tonsillectomy or follow-up alone. They were all followed up with symptom diaries for 12 months. Tonsillectomy was allowed after 6 months in the control group if the attacks recurred. RESULTS: Six months after randomization all 14 children in the tonsillectomy group and 6/12 children in the control group (50%) were free of symptoms (difference 50%, 95% confidence interval 23% to 75%, P < .001). Tonsillectomy was performed on 5/6 of the patients in the control group who still had symptoms after 6 months. The remaining unoperated child in the control group had recurrences of the fever episodes throughout the follow-up, but the symptoms became less severe, and the parents did not choose tonsillectomy. CONCLUSION: Tonsillectomy appeared to be effective for treating PFAPA syndrome. The fever episodes ceased without any intervention in half of the control subjects. We conclude that although the mechanisms behind this syndrome are unknown, tonsillectomy can be offered as an effective intervention for children with PFAPA. PMID- 17719942 TI - Effect of prebiotic supplementation and calcium intake on body mass index. AB - OBJECTIVE: To assess the effects of a prebiotic supplement and usual calcium intake on body composition changes during pubertal growth. STUDY DESIGN: We measured anthropometry and body fat with dual-energy X-ray absorptiometry in 97 young adolescents who were randomized to receive either a daily prebiotic supplement or maltodextrin (control) for 1 year. RESULTS: Subjects who received the prebiotic supplement had a smaller increase in body mass index (BMI) compared with the control group (BMI difference 0.52 +/- 0.16 kg/m2, P = .016), BMI Z score (difference 0.13 +/- 0.06, P = .048) and total fat mass (difference 0.84 +/ 0.36 kg, P = .022). The prebiotic group maintained their baseline BMI Z-score (0.03 +/- 0.01, paired t test, P = .30), although BMI Z-score increased significantly in the control group (0.13 +/- 0.03, P < .001). In considering subjects whose usual calcium intake was > or = 700 mg/d, those who received the prebiotic supplement had a relative change in BMI that was 0.82 kg/m2 less than control subjects (P < .01), and BMI Z-score that was 0.20 less than control subjects (P = .003). Differences tended to be maintained 1 year after supplementation was stopped. CONCLUSION: Prebiotic supplementation and avoidance of a low calcium intake can have significant effects in modulating BMI and other body composition changes during puberty. PMID- 17719943 TI - Long-term follow-up in 12 children with pulmonary arteriovenous malformations: confirmation of hereditary hemorrhagic telangiectasia in all cases. AB - OBJECTIVE: To assess whether pulmonary arteriovenous malformation (PAVM) is associated with hereditary hemorrhagic telangiectasia (HHT). STUDY DESIGN: This study was a review of 12 children (sex ratio = 1) including family history, mutation analysis, and long-term follow-up. RESULTS: Five children were under age 3 years when PAVM was diagnosed. Presentations included pulmonary symptoms (n = 8), cerebral abscess (n = 2), and transient ischemic attack (TIA) (n = 1); 1 patient was asymptomatic. Nine of the 12 children (75%) had a family history of PAVM. The diagnosis of HHT was confirmed in all cases. A mutation in ENG was found in 9 of the 10 children available for testing. No mutation in ACVRL1 was found. During long-term follow-up (mean, 16 years), the following complications occurred: TIA (n = 2), hemoptysis (n = 2), and cerebral abscess (n = 2). Nine children experienced recurrence of PAVM. The children with no recurrence were those without a family history of PAVM. CONCLUSIONS: The diagnosis of HHT should be considered in a child with an apparently isolated PAVM. Because serious complications may occur at any age, we recommend screening for PAVM and long-term follow-up in children from families with HHT, especially those with an ENG mutation. PMID- 17719945 TI - Duodenogastro-esophageal reflux in children with refractory gastro-esophageal reflux disease. AB - OBJECTIVE: To determine the role of duodenogastro-esophageal reflux (DGER) in the pathogenesis of refractory gastro-esophageal reflux disease (GERD) in children. STUDY DESIGN: Twenty-two patients (12 boys, mean age, 13.2 years) with GERD symptoms that persisted on omeprazole (1 mg/kg) underwent upper gastrointestinal endoscopy and barium x-ray, 24-hour pH and DGER (Bilitec) monitoring, and a 13C octanoic acid gastric emptying breath test. RESULTS: Patients presented mainly with epigastric pain, regurgitation, and nausea. Endoscopy revealed persistent esophagitis in 15 patients (68%). Pathologic acid and DGER exposure were present in 12 (55%) and 15 (68%) children, respectively, with combined pathologic reflux in 10 (45%). Acid exposure did not differ according to the presence of esophagitis, but patients with grade II esophagitis had significantly higher DGER exposure than those without esophagitis (9.1 +/- 5.3% vs 26.7 +/- 10.9% of the time, P < .05). Gastric emptying rate was not associated to acid or DGER exposure or persisting esophagitis. Symptoms improved after adding a prokinetic drug to the proton pump inhibitor therapy or referral for surgery (n = 5). CONCLUSIONS: DGER may play a role in the pathophysiology of proton pump inhibitor-refractory GERD and esophagitis in children. PMID- 17719946 TI - Vocal cord dysfunction and feeding difficulties after pediatric cardiovascular surgery. AB - OBJECTIVE: To evaluate the impact of vocal cord dysfunction on feeding in children after cardiovascular surgery. STUDY DESIGN: Of the 2255 children who had cardiovascular surgery between January 2000 to January 2006, 38 (1.7%) had postoperative vocal cord dysfunction confirmed at laryngoscopy. The following data were obtained retrospectively: type of surgery, laryngoscopic examination results, swallowing studies, upper gastrointestinal (UGI) studies, and feeding route: oral, nasogastric tube (NG), and gastrostomy. RESULTS: Surgeries included aortic arch reconstruction (n = 20), patent ductus arteriosus ligation (n = 8), arterial switch (n = 3), cervical cannulation for extracorporeal membrane oxygenation (n = 2), and others (n = 5). A swallowing study confirmed dysfunction in 27 of 29 patients. Gastrostomy was placed in 18/38 patients. At discharge, 18 patients were fed by gastrostomy, 13 orally, 3 by NG, and 4 by combination oral/NG. At a median follow-up of 12 months, 20 were fed orally, 1 by NG, 7 by gastrostomy, 7 by combination gastrostomy/orally, 1 was lost to follow-up, 2 died. CONCLUSION: Vocal cord dysfunction after pediatric cardiovascular surgery is associated with significant feeding problems and may require prolonged gastrostomy feeding. These findings support aggressive surveillance for vocal cord dysfunction, especially in patients undergoing aortic arch surgery. PMID- 17719947 TI - Growing skull fracture after minor closed-head injury. PMID- 17719948 TI - In vivo proton magnetic resonance spectroscopy assessment for muscle metabolism in neuromuscular diseases. AB - Muscle metabolites were obtained by in vivo proton magnetic resonance spectroscopy of 3 patients with Duchenne muscular dystrophy (DMD), 6 patients with spinal muscular atrophy (SMA), and 10 normal volunteers. Patients with DMD and SMA had lower trimethyl amide (TMA)/water and TMA/total creatine (tCr) ratios but normal tCr/water ratios. PMID- 17719949 TI - ABCA3 deficiency presenting as persistent pulmonary hypertension of the newborn. AB - A newborn with persistent pulmonary hypertension (PH) unresponsive to conventional therapies was found to be homozygous for a mutation in the gene encoding adenosine triphosphate binding cassette protein, member A3 (ABCA3). Most causes of PH respond to lung recruitment, inhaled nitric oxide, and hemodynamic support. When PH is prolonged and does not respond to standard therapies, genetic causes of surfactant abnormalities should be considered in the differential diagnosis. PMID- 17719951 TI - Predictive value of rapid influenza tests varies with prevalence. PMID- 17719950 TI - Severe cerebellar hypoplasia associated with osteogenesis imperfecta type III. PMID- 17719952 TI - Adenotonsillectomy less beneficial for sleep apnea in older and obese children. PMID- 17719953 TI - Failure to respond to name is indicator of possible autism spectrum disorder. PMID- 17719957 TI - Impact of combination therapy with repeat surgery and temozolomide for recurrent or progressive glioblastoma multiforme: a prospective trial. AB - BACKGROUND: The purpose of this study is to evaluate the feasibility of repeat surgery combination with postoperative TMZ for adults with recurrent or progressive GBMs. METHODS: Of 35 patients who had diagnoses of GBM between 2002 and 2005, 7 (20%) underwent second surgeries and TMZ for recurrent or progressive disease. We examined the case histories of these 7 patients and determined the location of tumor and extent of their surgical procedures. Using the KPS, we assessed each patient's neurologic state before and after initial and repeat surgery. We calculated survival times from time of initial surgery and compared actual survival with statistically predicted survival times for each patient. RESULTS: Median survival rates were higher than predicted: The statistical risk estimate for median survival time after repeat surgery for these patients was 9 months; the actual survival time from initial operation until time of death averaged 15.1 months. The neurologic status before and after second surgery also averaged 76 points on KPS. Survival time did not depend on removing the entire tumor at initial and second surgery. CONCLUSION: Combination with repeat surgery and TMZ improved overall survival of these GBM patients. PMID- 17719958 TI - Utility of new bioabsorptive screws in cervical anterior fusion. AB - BACKGROUND: The aim of this study is to report our use of new bioabsorbable screws in cervical anterior fusion. These screws need not be removed because they are completely absorbed by resolution in vivo. We describe our method and the new bioabsorbable screws. METHODS: We used PLLA screws until September 2004 and uncalcined uHA-PLLA screws thereafter. They are completely absorbed by resolution to water and carbon dioxide upon in vivo hydrolysis. The uHA-PLLA screws are x ray impenetrable, and their uHA content renders them osteoconductive. In cervical anterior fusion, the graft is inserted in the area of deletion resulting from decompression. The screws are inserted in the 4 corners of the vertebral body and graft. In long fusion, they are introduced in the 2 lateral wings of the bone graft on each vertebral body and in the 4 corners. Our method eliminates the need for plates or mesh. RESULTS: We have used this method in 62 patients and encountered no complications. There were no screw or graft extrusions and no surgery-related infections. The patients were able to walk a few hours after the operation and wore a simple neck collar for a few days. CONCLUSIONS: This safe and easy method shortens the hospital stay and reduces the risk of graft extrusion and complications associated with the use of nonabsorbable devices. PMID- 17719960 TI - A novel technique for the intraoperative monitoring of detrusor activity in intradural lesions of the cauda equina. Technical note. AB - BACKGROUND: Intradural pathology in the region of the cauda equina is uncommon and generally comes to attention secondary to pain or neurologic deficit. A number of surgeons choose to excise these lesions under EMG monitoring of the nerve roots supplying the lower extremity muscles, anal sphincter, and detrusor muscle. In this article, the authors describe a detrusor muscle monitoring technique that has been found to be simple, reliable, and cost-effective in the management of intradural pathology of the cauda equina. METHODS: Fourteen consecutive patients with tumors of the cauda equina who underwent surgical management performed using the standard Foley catheter monitoring technique were included in this study and their outcomes analyzed. RESULTS: In 86% of patients, a gross total resection was achieved. Subtotal resections were performed in 2 patients because of involvement of critical nerve roots. In all cases, the nerve roots supplying the detrusor muscle were successfully identified using this technique. No patient suffered a clinically apparent decline in bladder function during the postoperative period. CONCLUSION: The standard Foley catheter detrusor monitoring technique is a simple, reliable, and cost-effective method to identify and prevent injury to the sacral nerve roots innervating the urinary bladder during intradural exploration of the cauda equina. PMID- 17719963 TI - Histologic study of arteriovenous shunts in the normal dura mater adjacent to the transverse sinus. AB - BACKGROUND: Although AV shunts are known to exist in the normal dura mater, their histologic appearance has not been examined in detail. Arteriovenous shunts in the normal dura mater adjacent to the transverse sinus, the most frequent site of DAVFs, were studied histologically. METHODS: Normal dura mater adjacent to the transverse sinus was obtained from 8 cadavers. Each specimen was cut into approximately 4-microm-thick serial sections; these were stained by the elastic Masson method and examined under a light microscope. RESULTS: Of the 8 specimens, 5 harbored a total of 6 AV shunts; no shunts were found in the other 3 specimens. The shunts, located in the supratentorial (n = 1) and infratentorial dura mater (n = 4) and in the tentorium cerebelli (n = 1), were classified into 2 types. In direct-type shunts, the artery connected directly to the vein; the diameter of these shunts ranged from 40 to 80 microm. In indirect-type shunts, the artery and vein were parallel and were indirectly connected by a shunt vessel, producing an H shape. The diameter of these shunt vessels ranged from 30 to 45 microm. All 6 shunts were connected to veins or the venous lake; none connected directly to the transverse sinus. CONCLUSIONS: The existence of direct- and indirect-type AV shunts in the normal dura mater was confirmed histologically. Both types exhibited the histologic features of DAVFs, suggesting that AV shunts in the normal dura mater might be involved in the etiology of DAVFs. PMID- 17719966 TI - The relationship between venous hypertension and expression of vascular endothelial growth factor: hemodynamic and immunohistochemical examinations in a rat venous hypertension model. AB - BACKGROUND: Venous hypertension is regarded as an important factor in the pathogenesis of dural arteriovenous fistula (DAVF). We investigate histologic reaction of dural sinus under the condition of venous hypertension using a rat venous hypertension model to present hemodynamic and immunohistochemical effect in the development of DAVF. METHODS: Twenty-four Sprague-Dawley male rats were divided into venous hypertension and control groups. Venous hypertension was induced with a left common carotid artery-external jugular vein anastomosis and an occlusion of a right posterior facial vein. Measurements of systemic mean arterial pressure, draining vein pressure (DVP), and cerebral perfusion pressure (CPP) were conducted on the next day, at 7 days, and at 28 days after surgery, and the rats were killed for histologic examinations. RESULTS: Postoperative DVP increased significantly in venous hypertension group compared to control group (35 +/- 5 vs 13 +/- 2 mm Hg, P < .05). Increased DVP remained above 30 mm Hg throughout the observation period. Postoperative CPP decreased significantly in venous hypertension group compared to control group (49 +/- 8 vs 86 +/- 9 mm Hg, P < .05). In venous hypertension group, there was a significant difference between days 1 and 28 (49 +/- 8 vs 64 +/- 8 mm Hg, P < .05). Histologic examination revealed thickening of connective tissues, proliferation of fibroblasts, and strong expression of vascular endothelial growth factor (VEGF) in endothelium under venous hypertension condition. Immunostained VEGF cells decreased significantly from day 7 to day 28 (100 +/- 16 vs 72 +/- 19 cells, P < .05). A positive correlation was observed between DVP and VEGF expression (Pearson correlation coefficient; r = 0.671, P = .0017). There was a negative correlation between CPP and immunostained VEGF cells (r = -0.702, P = .0089). CONCLUSIONS: These results suggest that venous hypertension is associated with increased expression of VEGF, and a decreased CPP may have a potential effect in VEGF expression under venous hypertension condition. These factors are speculated to play an important role in progression of DAVF. PMID- 17719968 TI - Diffusion tensor-based fiber tracking and intraoperative neuronavigation for the resection of a brainstem cavernous angioma. AB - BACKGROUND: Surgical treatment of brainstem cavernous angioma involving eloquent fiber tracts is one of the most challenging areas of contemporary neurosurgery. Diffusion tensor imaging-based fiber tracking adds essential information for preoperative planning in neurosurgical practice. Integration of the tractography into neuronavigation system makes it possible for the intraoperative visualization of the major fiber tracts. It may help increase the likelihood of the total resection of tumors adjacent to the eloquent fiber tracts and avoid new neurologic deficits after surgery. CASE DESCRIPTION: We report our valuable experience of such integration for the resection of a deeply located brainstem cavernous angioma. CONCLUSION: Inclusion of tractography in standard imaging protocols for neuronavigation systems can provide important information regarding neural tracts for the planning of brainstem surgery. It can also increase the safety of neurosurgical intervention near white matter tracts in the brainstem. PMID- 17719970 TI - Detection of hemodynamic transient ischemic attack during hemodialysis with near infrared monitoring in a patient with internal carotid artery occlusion. AB - BACKGROUND: It is still difficult to directly prove the involvement of hemodynamic ischemia in ischemic attacks in patients with occlusive carotid artery diseases. CASE DESCRIPTION: In this report, we describe the case of a 52 year-old woman with right ICA occlusion who experienced repeated transient weakness of the left extremities during HD for chronic renal failure. Single photon emission computed tomography showed reductions in CBF and CVR to acetazolamide in the right hemisphere. Real-time NIRS monitoring clearly showed a deterioration in the cerebral oxygenation state in the right hemisphere in response to a BP decrease during HD. Superficial temporal artery-MCA anastomosis improved SPECT as well as NIRS findings and resolved ischemic attacks during HD. CONCLUSION: This is the first study to show that NIRS can be a useful tool in detecting hemodynamic ischemia in patients with impaired cerebral perfusion reserves noninvasively and in real time. PMID- 17719973 TI - Near-infrared spectroscopy as real-time monitor. PMID- 17719974 TI - Desmoplastic infantile ganglioglioma: novel aspects in clinical presentation and genetics. AB - BACKGROUND: Desmoplastic infantile ganglioglioma is a rare tumor occurring mainly in infants and young children. Both radiological and histopathological appearances may resemble malignancy, although its clinical course is mainly benign. METHODS: Altogether, 5 cases of DIG have been operated on in our hospital since the first diagnosis of DIG in Finland in 1993. We evaluated their presenting symptoms, radiological and surgical findings, histologic characteristics, and follow-up. RESULTS: All patients were male. Three were less than 18 months old, and 2 were 35 and 79 months old. The most common presenting symptoms were epileptic seizures (4 cases). In 4 cases, there was a histopathologically verified single cystic tumor. In 1 case, DIG was operatively diagnosed in 2 separate locations. This patient, moreover, had 2 other lesions suspected of being DIG, including a mass originating from the ophthalmic nerve. None of the patients received adjuvant therapies. All our patients are alive after 7 to 120 months of follow-up. There were no recurrences in any of the patients after tumor resection. For the first time, we describe EGFR and MYCN amplifications in tumors which are, respectively, of their mixed glial and neuronal origin. CONCLUSION: The clinical presentation of DIG may be more often associated with epileptic seizures than previously thought. The radiological appearance of DIG may vary from cystic to solid and from contrast-enhancing to nonenhancing. Even multiple locations of DIG have been encountered. Increasing evidence supports surgery as the treatment of choice for DIG, although oncogene amplifications have been described. PMID- 17719976 TI - Primary spinal intradural extramedullary cysticercosis. AB - BACKGROUND: Spinal cysticercosis represents an uncommon localization of a common parasitic disease and, in most cases, is associated with intracranial involvement. Once confirmed, the entire neuraxis should be evaluated. CASE DESCRIPTION: We present an unusual case of a 60-year-old male patient with isolated localization of spinal intradural extramedullary cysticercosis. The patient was treated successfully with the combination of surgical excision and orally administered albendanzole. We discuss the treatment options, the diagnostic screening, and the possible route of dissemination. CONCLUSIONS: Because this is a rare but potentially life-threatening disease, clinicians should always take it into consideration in the differential diagnosis of spinal space-occupying lesions. PMID- 17719978 TI - Epidermoid cyst of anterior fontanelle with clear contents. AB - BACKGROUND: Epidermal inclusion cysts very rarely occur in the midline in the area of the anterior fontanelle. CASE DESCRIPTION: We report the second case of epidermal inclusion cysts in the midline in the area of the anterior fontanelle in world literature of a 7-month female infant who presented with a slow-growing soft mass located in the midline over the vertex of the head. CONCLUSION: These lesions with clear contents can have all the features of encephalocele on clinical examination, and imaging will show the exact location, but histopathology will confirm the diagnosis. PMID- 17719980 TI - Severe postoperative vasculitis of the central nervous system in a child with arteriovenous malformation: case report. AB - BACKGROUND: Cerebral vasculitis is very rare complication after craniotomy. We report a case and discuss the etiology, diagnosis, and treatment of this complication. CASE DESCRIPTION: A 12-year-old boy was admitted because of a consciousness disturbance due to a ruptured AVM. Computed tomography revealed a left parietal subcortical hematoma. No apparent nidus was detected on the angiography findings, but AVM was suspected. After resection of the hematoma, the patient did not recover consciousness, and his high fever continued. Despite postoperative induced hypothermia, progressive multiple cerebral infarctions occurred. Postoperative angiography showed multiple arterial narrowing, and a "string of beads" phenomenon was observed in the anterior and posterior circulation in addition to the residual AVM. After administering steroid therapy, he recovered consciousness, but had a severe disability. After angiography, which was performed 1 year after onset, an improvement of the vasculitis and the complete occlusion of AVM were observed. CONCLUSION: We should therefore include cerebral vasculitis in the differential diagnosis when encountering a case with an unusual progressive stroke because a timely diagnosis and aggressive treatment are of critical importance for a successful recovery in such patients. PMID- 17719981 TI - Surgical treatment of giant fusiform aneurysm of extracranial internal carotid artery in a child: 1 case report and literature review. AB - BACKGROUND: The objective of this study is to report diagnosis and treatment results of giant fusiform aneurysm of extracranial internal carotid artery in a child and review the relative reference to enhance the knowledge of it. METHODS: A 13-year-old female patient was admitted to the hospital with chief complaint of pulsatile mass in her left cervical area for 1 year, which had abruptly augmented 2 months earlier. No cervical trauma or infection appeared. A 3.5 x 6-cm mass in the left cervical angle of the mandible was observed to beat with pulse without vascular murmur. Digital subtraction angiography and CTA showed a giant fusiform aneurysm 6 cm in length and 3 cm in maximum diameter from the beginning of the left internal carotid artery. After resection of the aneurysm, vascular continuity was restored by interposition of a 6-mm PTFE graft. RESULTS: Pathologic examinations showed hyperplasia in artery wall, fibroplasias and mucous degeneration, hyalinization, chronic inflammatory cell infiltration, and local calcification. The recovery was good without complication. The patient was followed up in 2 years postoperation. The CTA and color Doppler ultrasonography showed good configuration and distribution of the internal carotid artery and good circulation in vascular cavity. CONCLUSIONS: Giant fusiform aneurysm of extracranial internal carotid artery in children is rather rare. The main causes are atherosclerosis, infection and trauma, incurring by carotid endarterectomy, and the like. Most of the clinical manifestations are pulsatile nontender mass. It can cause severe complications, such as brain ischemia or cervical hematorrhea incurred by rupture of aneurysm. The therapy includes resection of the aneurysm and restoration of flow with venous, arterial, or prosthetic graft or endovascular stenting. PMID- 17719983 TI - Intracerebral hemorrhage after prophylactic revascularization in a patient with adult moyamoya disease. AB - BACKGROUND: The effect of revascularization surgery for a patient with moyamoya disease remains controversial. CASE DESCRIPTION: A 60-year-old man presented with bleeding from asymptomatic moyamoya vessels 10 years after prophylactic revascularization surgery. Cerebral angiography 10 years after the surgery demonstrated that the bilateral direct anastomoses remained effective and a small aneurysm persisted in the anterior choroidal artery. The territories of perfusion through the anastomoses and the size of the aneurysm remained unchanged compared with the angiograms performed 10 years ago. CONCLUSIONS: Direct revascularization surgery may not always resolve microaneurysms in the moyamoya vessels and prevent rebleeding in patients with hemorrhagic moyamoya disease or bleeding in the nonaffected side. PMID- 17719985 TI - Ruptured aneurysm of a persistent primitive hypoglossal artery treated by endovascular approach--case report and literature review. AB - BACKGROUND: A persistent PHA is the second most common of the embryonic carotid basilar anastomoses that fail to regress in the embryo. The fact that PHA often is functionally a single artery providing blood to the posterior circulation poses challenging therapeutic problems in case of an aneurysm located on the PHA. CASE DESCRIPTION: A 46-year-old woman presented with SAH due to a large ruptured aneurysm of the left PHA. Identification of such an artery by CT angiogram is the proposed cold standard. The aneurysm was obliterated by coil embolization. To our knowledge, this is the first reported case of aneurysm located on a primitive persistent hypoglossal artery that was endovascularly treated. CONCLUSION: Aneurysms located on a persistent PHA can be treated safely and effectively via an endovascular approach. PMID- 17719987 TI - The earliest document regarding the history of cranioplasty from the Ottoman era. AB - Cranioplasty is one of the significant neurosurgical procedures in which the technical advances and also, by some means, drawbacks are still continuing. According to archeological findings and anthropological studies, the earliest procedures regarding cranioplasty date back to just about the same period claimed for trepanation. Ancient surgeons from different geographical sites and cultures performed both practices with remarkable survival rates. However, despite the length of the thriving past of cranioplasty, the first known written record on the topic dates back to late 16th century Europe. Further study of the Ottoman era documents revealed an intriguing text that was written about the repair of skull defects and that dates from early 16th century. This worthy discovery will add valuable contribution to the history of neurosurgery by drawing the written history of cranioplasty more than 60 years back and the use of organic grafts 160 years back. In the present study, this original text is discussed. PMID- 17719989 TI - Leadership. PMID- 17719990 TI - Power: why we lost it. PMID- 17719991 TI - International neurosurgery--not a luxury, but a need! PMID- 17719992 TI - Humane and compassionate elder care as a human right. PMID- 17719993 TI - Can caring for patients be taught? PMID- 17719994 TI - Preventing chronic disease: a forthcoming initiative. PMID- 17719996 TI - Calcium and vitamin D for osteoporotic fracture risk. PMID- 17719997 TI - Acute myocardial infarction and diabetes. PMID- 17719998 TI - Catecholamine treatment for shock--equally good or bad? PMID- 17719999 TI - Speaking out about human rights and health in West Papua. PMID- 17720000 TI - Where have all the bees gone? PMID- 17720001 TI - Clinical update: obstetric anaesthesia. PMID- 17720002 TI - Dennis Carlson. PMID- 17720005 TI - Folic acid for stroke prevention. PMID- 17720006 TI - Recurrent anaphylaxis to synthetic folic acid. PMID- 17720007 TI - DFID's health strategy. PMID- 17720008 TI - Misleading confidence intervals. PMID- 17720010 TI - DFID's health strategy. PMID- 17720011 TI - Minimisation of immunosuppression in transplantation. PMID- 17720013 TI - Human resources in developing countries. PMID- 17720014 TI - MMC, Britain's aid deficit, and overseas health-care shortages. PMID- 17720016 TI - Quality of life in children with cerebral palsy. PMID- 17720017 TI - Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta analysis. AB - BACKGROUND: Whether calcium supplementation can reduce osteoporotic fractures is uncertain. We did a meta-analysis to include all the randomised trials in which calcium, or calcium in combination with vitamin D, was used to prevent fracture and osteoporotic bone loss. METHODS: We identified 29 randomised trials (n=63 897) using electronic databases, supplemented by a hand-search of reference lists, review articles, and conference abstracts. All randomised trials that recruited people aged 50 years or older were eligible. The main outcomes were fractures of all types and percentage change of bone-mineral density from baseline. Data were pooled by use of a random-effect model. FINDINGS: In trials that reported fracture as an outcome (17 trials, n=52 625), treatment was associated with a 12% risk reduction in fractures of all types (risk ratio 0.88, 95% CI 0.83-0.95; p=0.0004). In trials that reported bone-mineral density as an outcome (23 trials, n=41 419), the treatment was associated with a reduced rate of bone loss of 0.54% (0.35-0.73; p<0.0001) at the hip and 1.19% (0.76-1.61%; p<0.0001) in the spine. The fracture risk reduction was significantly greater (24%) in trials in which the compliance rate was high (p<0.0001). The treatment effect was better with calcium doses of 1200 mg or more than with doses less than 1200 mg (0.80 vs 0.94; p=0.006), and with vitamin D doses of 800 IU or more than with doses less than 800 IU (0.84 vs 0.87; p=0.03). INTERPRETATION: Evidence supports the use of calcium, or calcium in combination with vitamin D supplementation, in the preventive treatment of osteoporosis in people aged 50 years or older. For best therapeutic effect, we recommend minimum doses of 1200 mg of calcium, and 800 IU of vitamin D (for combined calcium plus vitamin D supplementation). PMID- 17720018 TI - Incidence of new-onset diabetes and impaired fasting glucose in patients with recent myocardial infarction and the effect of clinical and lifestyle risk factors. AB - BACKGROUND: Individuals with diabetes are at higher risk of myocardial infarction than non-diabetics. However, much less is known about the incidence of, and risk factors for, development of diabetes and impaired fasting glucose in patients who have had a myocardial infarction. We set out to estimate this incidence and investigate whether lifestyle factors such as dietary habits might alter this risk. METHODS: We used prospectively obtained data for 8291 Italian patients with a myocardial infarction within the previous 3 months, who were free of diabetes (determined by medication use, a physician-reported diagnosis, or fasting glucose > or =7 mmol/L) at baseline. Incidence of new-onset diabetes (new diabetes medication or fasting glucose > or =7 mmol/L) and impaired fasting glucose (fasting glucose > or =6.1 mmol/L and <7 mmol/L) were assessed at follow-up at 0.5, 1.0, 1.5, 2.5, and 3.5 years. Baseline data for body-mass index (BMI), other risk factors, dietary habits, and medications were updated during follow-up. A Mediterranean diet score was assigned according to consumption of cooked and raw vegetables, fruit, fish, and olive oil. Associations of demographic, clinical, and lifestyle risk-factors with incidence of diabetes and impaired fasting glucose were assessed with multivariable Cox proportional hazards. FINDINGS: During 26 795 person-years (mean follow-up 3.2 years [SD 0.9]), 998 individuals (12%) developed new-onset diabetes (incidence 37 cases per 1000 person-years). Of the 7533 without impaired fasting glucose at baseline, 2514 (33%) developed new onset impaired fasting glucose or diabetes (incidence 123 cases per 1000 person years), rising to 3859 (62%) of 6229 with the lower cutoff for impaired fasting glucose of 5.6 mmol/L (incidence 321 cases per 1000 person-years). Independent risk factors for new-onset diabetes or impaired fasting glucose included older age, hypertension, use of beta-blockers, lipid-lowering medications (protective), and diuretic use. Independent lifestyle risk-factors included higher BMI, greater BMI gain during follow-up, current smoking, a lower Mediterranean dietary score, and wine consumption of more than 1 L/day. Data for physical activity were unavailable, but inability to perform exercise testing was associated with higher incidence of diabetes and impaired fasting glucose. INTERPRETATION: Compared with population-based cohorts, patients with a recent myocardial infarction had a higher annual incidence rate of impaired fasting glucose (1.8 vs 27.5% in our study) and diabetes (0.8-1.6% compared with 3.7%) in this study. Thus, our results indicate that myocardial infarction could be a prediabetes risk equivalent. Smoking cessation, prevention of weight gain, and consumption of typical Mediterranean foods might lower this risk, which emphasises the need for guidance on diet and other lifestyle factors for patients who have had a myocardial infarction. PMID- 17720019 TI - Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. AB - BACKGROUND: International guidelines for management of septic shock recommend that dopamine or norepinephrine are preferable to epinephrine. However, no large comparative trial has yet been done. We aimed to compare the efficacy and safety of norepinephrine plus dobutamine (whenever needed) with those of epinephrine alone in septic shock. METHODS: This prospective, multicentre, randomised, double blind study was done in 330 patients with septic shock admitted to one of 19 participating intensive care units in France. Participants were assigned to receive epinephrine (n=161) or norepinephrine plus dobutamine (n=169), which were titrated to maintain mean blood pressure at 70 mm Hg or more. The primary outcome was 28-day all-cause mortality. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00148278. FINDINGS: There were no patients lost to follow-up; one patient withdrew consent after 3 days. At day 28, there were 64 (40%) deaths in the epinephrine group and 58 (34%) deaths in the norepinephrine plus dobutamine group (p=0.31; relative risk 0.86, 95% CI 0.65 1.14). There was no significant difference between the two groups in mortality rates at discharge from intensive care (75 [47%] deaths vs 75 [44%] deaths, p=0.69), at hospital discharge (84 [52%] vs 82 [49%], p=0.51), and by day 90 (84 [52%] vs 85 [50%], p=0.73), time to haemodynamic success (log-rank p=0.67), time to vasopressor withdrawal (log-rank p=0.09), and time course of SOFA score. Rates of serious adverse events were also similar. INTERPRETATION: There is no evidence for a difference in efficacy and safety between epinephrine alone and norepinephrine plus dobutamine for the management of septic shock. PMID- 17720020 TI - Polycystic ovary syndrome. AB - Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects about one in 15 women worldwide. The major endocrine disruption is excessive androgen secretion or activity, and a large proportion of women also have abnormal insulin activity. Many body systems are affected in polycystic ovary syndrome, resulting in several health complications, including menstrual dysfunction, infertility, hirsutism, acne, obesity, and metabolic syndrome. Women with this disorder have an established increased risk of developing type 2 diabetes and a still debated increased risk of cardiovascular disease. The diagnostic traits of polycystic ovary syndrome are hyperandrogenism, chronic anovulation, and polycystic ovaries, after exclusion of other conditions that cause these same features. A conclusive definition of the disorder and the importance of the three diagnostic criteria relative to each other remain controversial. The cause of polycystic ovary syndrome is unknown, but studies suggest a strong genetic component that is affected by gestational environment, lifestyle factors, or both. PMID- 17720022 TI - Inconvenient truths about effective clinical teaching. PMID- 17720021 TI - Violations of human rights: health practitioners as witnesses. AB - For humanitarian health-care practitioners bearing witness to violations of human dignity has become synonymous with denunciations, human rights advocacy, or lobbying for political change. A strict reliance on legal interpretations of humanitarianism and human rights is inadequate for fully understanding the problems inherent in political change. With examples from the HIV/AIDS epidemic in the USA, the Rwandan genocide, and physician-led political activism in Nepal, we describe three cases in which health practitioners bearing witness to humanitarian and human-rights issues have had imperfect outcomes. However these acts of bearing witness have been central to the promotion of humanitarianism and human rights, to the pursuit of justice that they have inevitably and implicitly endorsed, and thus to the politics that have or might yet address these issues. Despite the imperfections, bearing witness, having first-hand knowledge of humanitarian and human-rights principles and their limitations, and systematically collecting evidence of abuse, can be instrumental in tackling the forces that constrain the realisation of human health and dignity. PMID- 17720023 TI - Mysterious falls and a nasal voice. PMID- 17720027 TI - Schizophrenia: measurements of psychopathology. AB - A key problem in schizophrenia research is how to assess the effects of treatment interventions given the spectrum of schizophrenia symptoms and patients' functioning. Measuring symptoms is complex, because these symptoms cover a wide variety of psychopathologic domains. The commonly recognized domains are the positive, negative, cognitive, excitement, and depression domains. This article critically reviews some of the available assessment tools of these domains together with other associated syndromes. The instruments discussed cover the broad range of psychopathology found in patients who have schizophrenia. PMID- 17720026 TI - Epidemiology of schizophrenia: review of findings and myths. AB - By describing patterns of disease distribution within populations, identifying risk factors, and finding associations, epidemiologic studies have contributed to the current understanding of schizophrenia. Advanced paternal age and the association with autoimmune diseases are some of the newly described epidemiologic findings shaping the current definition of schizophrenia. Although early intervention strategies have gained momentum, primary prevention of schizophrenia still seems a very distant aspiration. This article reviews the major epidemiological features of schizophrenia, with particular attention to the recent advances using population-based data. It also discusses some pervasive misconceptions about schizophrenia epidemiology, such as universal distribution and gender equality. PMID- 17720028 TI - Functional genomics and schizophrenia: endophenotypes and mutant models. AB - This article summarizes the rationale, methods, and results of gene discovery programs in schizophrenia research and describes functional methods of investigating potential candidate genes. It focuses next on the most prominent current candidate genes and describes (1) evidence for their association with schizophrenia and research into the function of each gene; (2) investigation of the clinical phenotypes and endophenotypes associated with each gene, at the levels of psychopathologic, neurocognitive, electrophysiologic, neuroimaging, and neuropathologic findings; and (3) research into the ethologic, cognitive, social, and psychopharmacologic phenotype of mutants with targeted deletion of each gene. It examines gene-gene and gene-environment interactions. Finally, it looks at future directions for research. PMID- 17720029 TI - Real-world antipsychotic treatment practices. AB - This article examines real-world antipsychotic use in the treatment of schizophrenia by comparing real-world prescribing with medication algorithms and guidelines, by evaluating the evidence underlying recommendations and guidelines, and by examining the roles of side effects and medication adherence in real-world prescribing decisions. PMID- 17720030 TI - Pharmacogenetics and schizophrenia. AB - Emergent pharmacogenetic studies indicate that the efficacy of antipsychotic medications in schizophrenia may be predicted through genetic analysis. There also is evidence that the side-effect profiles of second-generation antipsychotic medications and their propensity to cause weight gain, glucose and lipid abnormalities, and tardive dyskinesia may be predicted by pharmacogenetic analysis in this patient population. In the future, this targeted approach with the choice of antipsychotic medication based on the likelihood of clinical response and development of side effects in light of a particular patient's genetic status may gain hold as new treatments are developed with even fewer side effects. PMID- 17720031 TI - Antipsychotic medication adherence in schizophrenia. AB - For individuals who have schizophrenia, adherence to medication is often poor, and stopping medication often has serious consequences. This article provides an update on recent literature regarding the frequency, clinical and social impact, and clinical correlates of nonadherence to antipsychotic medication in schizophrenia. The authors then review published trials of interventions to improve adherence in schizophrenia. PMID- 17720032 TI - Reaching for wellness in schizophrenia. AB - Coronary heart disease (CHD) is a major cause of mortality in people who have schizophrenia, and it is caused by many factors relating to lifestyle choices, antipsychotic treatment, and other medical comorbidities. This article focuses on modifiable risk factors such as cigarette smoking, diabetes, hyperlipidemia, hypertension, and the metabolic syndrome, all of which occur more frequently in patients who have schizophrenia than in the general population. Although treatment of risk factors for CHD is still far from ideal, all attempts should be made to strive for wellness to improve patients' long-term outcomes. PMID- 17720033 TI - Understanding and treating "first-episode" schizophrenia. AB - "First-episode schizophrenia" is a clinical and research term that often is used to emphasize the special issues that arise when working with this patient population. The notion that schizophrenia has an inexorable downhill course or is a deteriorating illness is being challenged by more sophisticated understanding of what happens before the initial episode and new understanding of the interactions between biologic vulnerabilities and specific environmental risk during adolescence and early adulthood, such as marijuana use. While the incidence rate of "first-episode" will make this a relatively small percentage of a usual clinical caseload, it is a critically important time for the future course of the illness. The hope is that proper management during this critical period will favorably influence the long-term trajectory of outcome for this individual patient. A growing body of evidence suggests that certain approaches and interventions are more helpful than others, such as understanding of the overwhelming nature of the experience to patients and families, aiming to achieve a full and broad pharmacologic response to initial antipsychotic therapy, while also being on the lookout for vulnerability and extreme sensitivity to side effects, and to anticipate a high likelihood of premature medication discontinuation. Clinicians and treatment services should try to identify "first episode" patients in time to be able to anticipate and address these issues. PMID- 17720034 TI - Treatment-resistant schizophrenia. AB - This article opens with a brief history of pharmacologic treatment of schizophrenia. It then discusses the definition and treatment of treatment resistant schizophrenia, with particular attention to clinical, biological and neuroimaging correlates, as well as the best treatment options, including the use of clozapine in patients who meet the definition of treatment-resistant schizophrenia. PMID- 17720035 TI - Rehabilitation and recovery in schizophrenia. AB - The combination of new medications and effective psychosocial rehabilitation interventions has the potential to improve outcomes for individuals with schizophrenia significantly. Patients who have persistent positive symptoms can benefit from cognitive behavior therapy. Impairments in social competence can be addressed with social skills training. Supported employment programs may increase the ability of patients who have schizophrenia to obtain competitive employment. Family psychoeducational approaches, treatments for comorbid substance abuse, and cognitive rehabilitation approaches that enhance or bypass impairments in cognitive functioning are discussed. This article describes current efforts to incorporate these evidence-based principles of rehabilitative medicine into the management of schizophrenia. PMID- 17720036 TI - Families and schizophrenia: the view from advocacy. AB - Historically, families of persons who have schizophrenia often were blamed for the development of the condition and subsequently might have been excluded from care. Now these notions, which never had much systematic empiric support, have been abandoned. Family involvement often is critical to the recovery process and must be engaged actively whenever possible. This article calls for the inclusion of patients who have schizophrenia and their families in a redesigned model of care that is explicitly collaborative in its orientation and routinely includes evidence-based treatments that are informed by a vision of recovery. PMID- 17720037 TI - Recovery and systems transformation for schizophrenia. AB - The Recovery Movement, initiated in the 1990s by mental health consumer groups and leaders, has emerged as a major force in the mental health field. This movement has been gaining strength and promises to impact mental health service delivery through innovations in care that other models of care have not offered. Recent efforts to conceptualize and study recovery empirically have bolstered the movement from a scientific standpoint. This article reviews the growing literature regarding recovery, offers a conceptual framework for understanding recovery, and discusses a specific manner in which systems transformation has begun to occur. PMID- 17720039 TI - Pathogenesis of chronic obstructive pulmonary disease. AB - The pathogenesis of chronic obstructive pulmonary disease (COPD) encompasses a number of injurious processes, including an abnormal inflammatory response in the lungs to inhaled particles and gases. Other processes, such as failure to resolve inflammation, abnormal cell repair, apoptosis, abnormal cellular maintenance programs, extracellular matrix destruction (protease/antiprotease imbalance), and oxidative stress (oxidant/antioxidant imbalance) also have a role. The inflammatory responses to the inhalation of active and passive tobacco smoke and urban and rural air pollution are modified by genetic and epigenetic factors. The subsequent chronic inflammatory responses lead to mucus hypersecretion, airway remodeling, and alveolar destruction. This article provides an update on the cellular and molecular mechanisms of these processes in the pathogenesis of COPD. PMID- 17720040 TI - Predictors of mortality in chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease (COPD) has become a major and growing health problem, with a mortality rate that continues to increase. Several factors, have been identified as individual predictors of mortality in COPD. This article reviews individual predictors for mortality. It also discusses the ability of an integrated, multidimensional tool to more broadly characterize COPD severity, assess response to therapeutic interventions and exacerbations, and predict mortality. PMID- 17720041 TI - The biology of a chronic obstructive pulmonary disease exacerbation. AB - Much of the morbidity and mortality in chronic obstructive pulmonary disease relates to symptomatic deteriorations in respiratory health termed exacerbations. Exacerbations also are associated with changes in lung function and both airway and systemic inflammation. The most common causes of exacerbation are micro organisms: respiratory viruses such as rhinovirus, and various bacterial species. This article reviews and discusses current understanding of the biology of exacerbations, considering the definition, epidemiology, etiology, and the nature and evolution of the changes in symptoms, lung function, and inflammation that characterize these important events. PMID- 17720042 TI - Systemic inflammation and skeletal muscle dysfunction in chronic obstructive pulmonary disease: state of the art and novel insights in regulation of muscle plasticity. AB - Systemic inflammation is a recognized hallmark of chronic obstructive pulmonary disease pathogenesis. Although the origin and mechanisms responsible for the persistent chronic inflammatory process remain to be elucidated, it is recognized that it plays an important role in skeletal muscle pathology as observed in chronic obstructive pulmonary disease and several other chronic inflammatory disorders. This article describes state-of-the-art knowledge and novel insights in the role of inflammatory processes on several aspects of inflammation-related skeletal muscle pathology and offers new insights in therapeutic perspectives. PMID- 17720043 TI - Other systemic manifestations of chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease (COPD) no longer is regarded simply as a disease of the lungs and airways. There is growing awareness of the multisystemic nature of this disease. Research has shown increased levels of systemic inflammation and cardiovascular, neurologic, psychiatric, and endocrine system dysfunction associated with COPD. Skeletal muscle dysfunction associated with COPD is discussed in the article by Schols in this issue of Clinics in Chest Medicine. In this article, other systemic manifestations of COPD are discussed. Although this field is expanding rapidly, this article focuses on recent advances and reviews. PMID- 17720044 TI - Environmental tobacco smoke: respiratory and other health effects. AB - Involuntary exposure to environmental tobacco smoke (ETS) is a serious and entirely preventable public health hazard. It has become clear that ETS adversely affects the health of all who breathe its toxins. Independent of active smoking, ETS exposure is a modifiable risk factor for chronic obstructive pulmonary disease. The expanding body of research presented in this article provides evidence that the damaging consequences of ETS reach far beyond the lungs. Having been determined the third leading cause of preventable death in this country, this is a problem that must be addressed aggressively. PMID- 17720045 TI - Chronic obstructive pulmonary disease in patients who have HIV infection. AB - An increased prevalence of chronic obstructive pulmonary disease (COPD) among persons who have HIV infection has raised the possibility that HIV may predispose to the development or progression of COPD. This article reviews the evidence that supports an association between HIV infection and COPD-namely emphysema and chronic bronchitis-and studies that suggest an association between HIV infection and small airways abnormalities and nonspecific airway hyper-responsiveness. Risk factors for COPD and potential reasons for an increased risk for COPD in HIV positive patients are discussed. In addition, issues in the management of COPD in HIV-positive patients are reviewed. PMID- 17720046 TI - Update on the pharmacologic therapy for chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease is a treatable disease characterized by progressive airflow limitation. Prevention of disease progression; improvement of symptoms, exercise tolerance, and health status; and decrease in exacerbations and mortality are the goals of management. Inhaled short-acting bronchodilators are recommended for symptoms in mild disease, whereas inhaled long-acting bronchodilators are recommended for maintenance therapy of daily symptoms. When symptoms are not controlled using one bronchodilator, combining bronchodilators may be more effective. Combining a long-acting beta-agonist with an inhaled corticosteroid is more effective than either agent alone. Several novel therapies are in different stages of development. PMID- 17720047 TI - Disease modification in chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease in which patients experience a progressive decline in lung function, worsening exercise capacity, and frequent exacerbations. Based on clinical evidence, the progression of COPD could be modified by focus on earlier diagnosis; risk reduction through smoking cessation; symptom reduction with pharmacotherapy, improving health-related quality of life, and pulmonary rehabilitation; and decreasing complications by reducing exacerbations. Smoking cessation has been shown to slow lung function decline and reduce mortality, including deaths due to cardiovascular disease, lung cancer, and other respiratory disease (including COPD). PMID- 17720048 TI - Self-management strategies in chronic obstructive pulmonary disease. AB - This article enables the reader to understand the newest scientific concepts and advances in the field of self-management in chronic obstructive pulmonary disease, recognize the importance of self-management education and what might be needed to enhance behavior modification, and translate these advances into strategies and specific interventions in clinical practice. PMID- 17720049 TI - New approaches in pulmonary rehabilitation. AB - Patients who have mild to severe chronic obstructive pulmonary disease may obtain improvement in dyspnea, exercise capacity, and health-related quality of life as a result of exercise training. The type and intensity of training is of key importance in determining outcomes. High-intensity aerobic training leads to physiologic gains in aerobic fitness. Nevertheless, extreme breathlessness or peripheral muscle fatigue may prevent some patients from performing high intensity exercise; therefore, new tools are needed to improve the effectiveness of pulmonary rehabilitation. PMID- 17720050 TI - Update in surgical therapy for chronic obstructive pulmonary disease. AB - Bullectomy for giant bullae, lung volume reduction surgery, and lung transplantation are three surgical therapies that may benefit highly selected patients with advanced chronic obstructive pulmonary disease. In this article, each procedure is reviewed, with an emphasis on guidelines for patient selection and clinical outcomes for the practicing pulmonologist. Recent results from the National Emphysema Treatment Trial, updated International Society for Heart and Lung Transplantation Registry data, and revised guidelines for patient selection for lung transplantation are discussed. PMID- 17720051 TI - Hysteresis: new mechanospeak for the ophthalmologist. PMID- 17720052 TI - Burst-shot infrared digital photography for measuring low-light pupil. PMID- 17720054 TI - Hydration behavior of porcine cornea crosslinked with riboflavin and ultraviolet A. PMID- 17720056 TI - Pupil dilation with intracameral lidocaine during phacoemulsification. PMID- 17720057 TI - Consultation section. Refractive surgical problem. PMID- 17720063 TI - Management of the hard posterior polar cataract. AB - I describe a technique for managing the posterior polar cataract with a dense nucleus by initially sculpting a central trough to the depth of the polar opacity. The nucleus is partially cracked in the periphery, avoiding the polar opacity, and then chopped into quadrants without rotating. Next, the phaco tip engages the core of the nuclear quadrant while a cleavage plane is manually dissected along the lenticular lamellae using a Nagahara phaco chopper, with the tip rotated slightly so it points somewhat toward the equator of the lens, to a depth estimated to leave a nuclear shell, sparing the polar cataract. The nucleus is peeled away from the outer nucleus shell, which is kept in place by the phaco chopper. The intact nuclear plate is removed last and any capsular defect managed accordingly. This technique minimizes the risk for losing a nuclear fragment into the vitreous cavity. PMID- 17720064 TI - Subbasal nerve fiber regeneration after LASIK and LASEK assessed by noncontact esthesiometry and in vivo confocal microscopy: prospective study. AB - PURPOSE: To evaluate recovery of the corneal subbasal nerve plexus and corneal sensitivity after myopic laser in situ keratomileusis (LASIK) and laser-assisted subepithelial keratectomy (LASEK). SETTING: Manchester Centre for Vision, Royal Eye Hospital, Manchester, United Kingdom. METHODS: Thirty LASEK patients and 20 LASIK patients had slit-scanning confocal microscopy and noncontact corneal esthesiometry preoperatively and 1, 3, and 6 months after surgery. Images of the subbasal nerve plexus were analyzed using customized software to evaluate nerve regeneration. RESULTS: Central corneal sensitivity decreased significantly 1 month after LASEK and LASIK and returned to normal levels after 3 months. Corneal subbasal nerve fiber density, nerve branch density, nerve fiber length, and nerve fiber width decreased significantly 1 month after LASIK and had not returned to the preoperative levels by 6 months. Nerve fiber tortuosity decreased significantly 1 month after LASEK and returned to the preoperative levels 3 months after surgery. There were no significant differences in nerve fiber tortuosity before and after LASIK. Neither corneal sensitivity nor nerve fiber morphology was different between the 2 groups at any postoperative visit. CONCLUSIONS: Corneal sensitivity and subbasal nerve morphology were adversely affected by LASEK and LASIK. Corneal sensitivity recovered 3 months after the procedure, but subbasal nerves were still abnormal after 6 months. Despite the different forms of surgical trauma to corneal nerves with LASIK and LASEK, there was no apparent difference in the time course of recovery of corneal structure and function. PMID- 17720065 TI - Effects of misalignment during corneal topography. AB - PURPOSE: To evaluate consequences of misalignment during corneal topography. SETTING: Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada. METHODS: Twenty nine healthy subjects were enrolled in a study of 2 types of misalignment during Orbscan topography acquisition. The first was rotation, which was defined as angular deviation of the subject's visual axis away from the central fixation target, and the second was translation, defined as off-center displacement of the joined half slits on the computer screen during alignment by the technician. The effect of vertical and horizontal misalignments, by rotation or translation, was assessed. Study parameters included simulated keratometries (SimKs), mean corneal power (mean power), and corneal apex (R) and the asphericity factor (Q) values. Inferior-superior (I-S) and temporal-nasal (T-N) indices were calculated. Differences in parameter values between aligned and misaligned positions were studied. A mathematical model was also developed to simulate rotational and translational misalignment and consolidate clinical experimentation. RESULTS: The mean SimK values were slightly but significantly affected by rotation. The I-S value increased significantly with downward rotation and decreased with upward rotation of the eye, while T-N values increased significantly with temporal rotation and decreased with nasal rotation. The R and Q values increased with rotation. Overall, the topography parameters were minimally affected by translation. Comparable results were obtained with the theoretical model. CONCLUSIONS: Rotational misalignment of the eye during acquisition influenced topography more than the translational misalignment during focusing by the technician. Rotational misalignment induced corneal asymmetry on elevation and curvature maps as well as pseudokeratoconus patterns. PMID- 17720066 TI - Analysis of ectasia after laser in situ keratomileusis: risk factors. AB - PURPOSE: To examine a database of laser in situ keratomileusis (LASIK) procedures for preoperative and operative factors assumed to increase the risk for developing post-LASIK ectasia. SETTING: Private clinical practice. METHODS: A computer database was queried for eyes that had LASIK for myopic refractive errors with the following characteristics: preoperative corneal thickness 500 microm or less, mean keratometry greater than 47.0 diopters (D), patient age 25 years or younger, attempted correction greater than -8.0 D, refractive astigmatism not with-the-rule and greater than 2.0 D, and residual stromal bed thickness (RST) 250 microm or less. Flap thickness and RST were measured using ultrasound pachymetry. All recorded information was exported to MS Excel and analyzed for eyes that had ectasia. RESULTS: Of the 9700 eyes in the database, none with the above characteristics developed ectasia over mean follow-up periods exceeding 2 years. Seven eyes had multiple risk factors without ectasia. Three eyes with abnormal preoperative topography developed ectasia. CONCLUSIONS: Individual preoperative and operative factors did not in and of themselves increase the risk for ectasia. Unmeasured and unknown factors that affect the individual cornea's biomechanical stability, in combination with some suspected risk factors as well as the current inability to identify corneas at risk for developing ectatic disorders, probably account for most eyes that develop ectasia today. PMID- 17720067 TI - In vivo pharmacokinetics and in vitro pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac. AB - PURPOSE: To evaluate the aqueous humor concentrations and cyclooxygenase (COX) inhibitory activities of nepafenac, amfenac, ketorolac, and bromfenac after topical ocular administration of Nevanac (nepafenac 0.1%), Acular LS (ketorolac 0.4%), or Xibrom (bromfenac 0.09%). SETTING: Five private ophthalmology practices throughout the United States. METHODS: Patients requiring cataract extraction were randomized to 1 of 3 treatment groups: Nevanac, Acular LS, or Xibrom. Patients were administered 1 drop of the test drug 30, 60, 120, 180, or 240 minutes before cataract surgery. At the time of paracentesis, an aqueous humor sample was collected and later analyzed for drug concentration. In addition, COX 1 (homeostatic) and COX-2 (inducible) inhibitory activities of nepafenac, amfenac, ketorolac, and bromfenac were determined via the in vitro measurement of prostaglandin E(2) (PGE(2)) inhibition. RESULTS: Seventy-five patients participated in the study. The prodrug nepafenac had the shortest time to peak concentration and the greatest peak aqueous humor concentration (C(max)). The C(max) of nepafenac was significantly higher than that of the other drugs (P<.05), including the higher-concentration ketorolac (0.4%). The area under the curve (AUC) of nepafenac was significantly higher (P<.05) than the AUCs of amfenac, ketorolac, and bromfenac. The combined AUCs of nepafenac and amfenac were the highest of all drugs tested (P<.05). Ketorolac showed the most potent COX-1 inhibition, whereas amfenac was the most potent COX-2 inhibitor. The PGE(2) aqueous humor levels of each study medication were highly variable; as a result, meaningful interpretation of the data was not possible. CONCLUSION: Nepafenac showed significantly greater ocular bioavailability and amfenac demonstrated greater potency at COX-2 inhibition than ketorolac or bromfenac. PMID- 17720068 TI - Incidence of visually significant pseudophakic macular edema after uneventful phacoemulsification in patients treated with nepafenac. AB - PURPOSE: To compare the incidence of visually significant pseudophakic macular edema after uneventful phacoemulsification in patients treated postoperatively with topical prednisolone and those treated with topical prednisolone and nepafenac 0.1% suspension (Nevanac). SETTING: Edward S. Harkness Eye Institute of Columbia University, New York, New York, USA. METHODS: This retrospective chart review was of consecutive patients who had phacoemulsification at a single institute and were given topical prednisolone alone or topical prednisolone and nepafenac to prevent cystoid macular edema. Data collection included preexisting ocular and systemic diseases, concurrent use of ocular and systemic medications, surgical technique, intraoperative and postoperative complications, follow-up visual and ocular assessments, and postoperative optical coherence tomography (OCT) assessment for macular edema. RESULTS: Postoperatively, 240 patients were treated with prednisolone and 210 patients, with prednisolone-nepafenac. Preoperatively, the 2 groups were demographically and clinically comparable in sex distribution (P = .8400), history of diabetes (P = .7267), hypertension or cardiac disease (P = .8690), and concurrent use of oral nonsteroidal anti inflammatory drugs (P = .7303). Iris manipulation was done in 16 patients in the prednisolone-alone group and 10 patients in the prednisolone-nepafenac group (P = .3876). Capsule staining was done in 5 patients and 4 patients, respectively. All patients were followed for at least 1 month postoperatively. Visually significant pseudophakic macular edema was documented by OCT in 5 patients treated with prednisolone alone and in no patients treated with prednisolone and nepafenac (P = .0354). No significant intraoperative or postoperative complications were reported. CONCLUSION: Patients treated with topical prednisolone alone had a significantly higher incidence of visually significant pseudophakic macular edema after uneventful cataract surgery than those treated with topical prednisolone and nepafenac. PMID- 17720069 TI - Clinical pseudophakic cystoid macular edema. Risk factors for development and duration after treatment. AB - PURPOSE: To characterize the incidence, duration, and risk factors for and outcome of cystoid macular edema (CME) after cataract surgery and investigate the effects of treatment regimens on visual outcome and duration. SETTING: University based comprehensive ophthalmology practice. METHODS: This study included 1659 consecutive cataract surgeries performed by residents between 2001 and 2006. Cases were classified according to the presence of CME. Subset analysis excluded patients with diabetes mellitus (DM). The CME groups were analyzed according to type of treatment to compare duration of CME and final best corrected visual acuity. RESULTS: The incidence of postoperative CME was 2.35% (39/1659), and history of retinal vein occlusion (RVO) was predictive of postoperative CME (odds ratio [OR], 47.12; P<.001). When patients with DM were excluded, the incidence of CME was 2.14% (29/1357) and history of RVO (OR, 31.75; P<.001), epiretinal membrane (ERM) (OR, 4.93; P<.03), and preoperative prostaglandin use (OR, 12.45; P<.04) were predictive of postoperative CME. Patients with DM and/or intraoperative complications did not have an increased risk for CME when treated with prophylactic postoperative nonsteroidal antiinflammatory drugs (NSAIDs) for 3 months. Groups treated with NSAIDs plus a steroid had significantly shorter resolution times than the untreated group (P = .004). CONCLUSIONS: A history of RVO, ERM, and preoperative prostaglandin use were associated with an increased risk for pseudophakic CME. Treatment with NSAIDs plus steroids was associated with faster resolution of CME than no treatment. Treating high-risk patients with NSAIDs after cataract surgery decreases the incidence of postoperative CME to that of patients who are not at high risk. PMID- 17720070 TI - Binocular implantation of the Tecnis Z9000 or AcrySof MA60AC intraocular lens in routine cataract surgery: prospective randomized controlled trial comparing VF-14 scores. AB - PURPOSE: To compare vision-related quality of life after binocular implantation of the Tecnis Z9000 intraocular lens (IOL) (Advanced Medical Optics) or the AcrySof MA60AC IOL (Alcon). SETTING: Moorfields Eye Hospital, London, United Kingdom. METHODS: The study was a double-masked prospective randomized controlled trial. The main outcome measure was the percentage of patients achieving a Visual Function-14 (VF-14) score of 90 or higher. Additional outcome measures were dysphotopsia symptom scores, a 5-point subjective grading of overall satisfaction, refraction, photopic and mesopic best corrected visual acuities, uncorrected visual acuity, Pelli-Robson contrast sensitivity, aberrometry, infrared pupillometry, and evaluation of posterior capsule opacification scores. RESULTS: Seventy-nine patients who had bilateral implantation of the Z9000 IOL and 100 patients who had bilateral implantation of the MA60AC IOL were assessed a mean of 7.9 months +/- 2.9 (SD) (range 4 to 16 months) after second-eye surgery. Spherical aberration (mean: Z9000, 0.00 microm +/- 0.06 [SD]; MA60AC, +0.14 +/- 0.09 microm) and root mean square scores for higher-order aberrations combined (mean: Z9000, 0.26 +/- 0.11 microm; MA60AC, 0.32 +/- 0.14 microm) were significantly lower in patients with the Z9000 IOL (P<.001 and P = .007, respectively). The VF-14 scores were 90 or higher in 96.2% of Z9000 patients and 90.0% of MA60AC patients (P = .15). It is unlikely that this weak trend in favor of the Z9000 IOL was clinically significant. The VF-14 scores were heavily skewed toward a perfect outcome and similarly distributed in both groups (median 100; interquartile range 98 to 100). Results for all other outcomes, including measures of acuity, were similarly distributed in Z9000 patients and MA60AC patients. CONCLUSIONS: The Z9000 IOL reduced spherical aberration compared with the MA60AC IOL. No improvement in subjective visual function using the VF-14 questionnaire was detected. PMID- 17720071 TI - Visual and optical performance of the Akreos Adapt Advanced Optics and Tecnis Z9000 intraocular lenses: Swedish multicenter study. AB - PURPOSE: To compare the subjective visual and objective optical performance of 2 aspherical intraocular lenses (IOLs), the Akreos Adapt Advanced Optics (AO) (Bausch & Lomb, Inc.) and the Tecnis Z9000 (Advanced Medical Optics, Inc.). SETTING: Four university hospitals in Sweden. METHODS: This study comprised 80 patients, 20 each from 4 university hospital centers in Sweden. All patients had bilateral clear corneal phacoemulsification with implantation of an Akreos Adapt AO IOL in 1 eye and Tecnis Z9000 IOL in the other eye according to a randomization protocol. Preoperatively, 90% contrast Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity was measured and the mesopic pupil sizes were determined. Ten to 12 weeks postoperatively, 12.5% and 90% contrast ETDRS visual acuities and photopic and mesopic Functional Acuity Contrast Test chart contrast sensitivities were determined. Wavefront analysis was performed with the Zywave II aberrometer (Bausch & Lomb, Inc.), and a questionnaire on the subjective quality of vision was completed by each patient. RESULTS: The Akreos AO IOL and Tecnis Z9000 IOL produced similar high- and low-contrast visual acuities as well as photopic and mesopic contrast sensitivities. The Tecnis Z9000 IOL resulted in lower spherical aberrations of the eye (mean 0.05 +/- 0.13 microm versus 0.35 +/- 0.13 microm root mean square, 6.0 mm pupil) (P<.001); however, the Akreos AO IOL provided a larger depth of field (mean 1.22 diopter [D] +/- 0.48 [SD] versus 0.86 +/- 0.50 D, 6.0 mm pupil) (P<.001). Patient satisfaction was generally high, although 68.8% of the patients reported some type of visual disturbance postoperatively. Twenty-eight percent of patients reported better subjective visual quality in the Akreos AO eye and 14%, in the Tecnis Z9000 eye (P<.0001). Accordingly, 33% perceived more visual disturbances in the Tecnis Z9000 eye and 11%, in the Akreos AO eye (P<.0001). CONCLUSIONS: Maximum reduction of spherical aberration did not maximize subjective visual quality. The higher perceived quality of vision with the Akreos AO IOL could be because of differences in depth of field, IOL material, or IOL design. PMID- 17720072 TI - Validity of autorefraction after cataract surgery with multifocal ReZoom intraocular lens implantation. AB - PURPOSE: To evaluate the clinical utility of spherocylindrical automated refraction (AR) compared with subjective manifest refraction (MR) after cataract surgery with implantation of ReZoom refractive multifocal intraocular lenses (IOLs) (Advanced Medical Optics, Inc.). SETTING: Private Practice. METHODS: This prospective nonrandomized interventional study consisted of 72 patients with bilateral cataract and a potential visual acuity of at least 20/40. Patients had bilateral nonsimultaneous cataract surgery and implantation of a ReZoom IOL. Manifest refraction was performed in all patients followed by 3 consecutive measurements using the Topcon KR-8000 autorefractor with nondilated and dilated pupils. Assessment of repeatability of multiple consecutive ARs and comparison of the AR and MR using power vector analysis were performed at the 6-month follow up. The main outcome measures were the correlation between AR and MR with sphere, spherical equivalent, and astigmatism as well as the repeatability of AR before and after dilation with phenylephrine 10%. RESULTS: Repeatability analysis showed that the initial nondilated AR was not significantly different from the mean of the 3 refractions for nondilated and dilated measurements. The mean difference between the initial AR and the MR was -0.84 +/- 0.62 diopters (D) for sphere (SD), -1.00 +/- 0.61 D for spherical equivalent, and -0.06 +/- 0.19 D and -0.01 +/- 0.17 D, respectively, for J(0) and J(45), the 2 components of astigmatism. Linear regression of AR versus MR data showed poor correlation for sphere (R(2) = 0.4852) and spherical equivalent (R(2) = 0.5529), whereas the correlation for the 2 astigmatic components of vector analysis was excellent (J(0), R(2) = 0.8881; J(45), R(2) = 0.8640). Correlation was better when the MR residual refractive defect was higher. CONCLUSIONS: Although autorefraction showed excellent agreement with subjective refractive astigmatism, correlation with spherical values was poor, with a trend toward more negative values. Autorefraction after ReZoom IOL implantation can be used as a good starting point for subjective refraction of astigmatism; however, spherical values should be underestimated. PMID- 17720073 TI - Posterior chamber phakic intraocular lens (ICL) for hyperopia: ten-year follow up. AB - PURPOSE: To evaluate the long-term safety, efficacy, predictability, and stability of implantation of a Collamer implantable contact lens (ICL) (Staar) to correct hyperopic refractive errors. SETTINGS: Ophthalmology Department, Santa Rita Hospital, Vercelli, Italy. METHODS: Fifty-nine eyes of 34 patients with hyperopia had implantation of an ICL. Patients were examined preoperatively (baseline) and 1 day, 1 week, 1, 3, and 6 months, and 1, 2, 4, 6, 8, and 10 years postoperatively. Main outcome measures were subjective and objective refractions, uncorrected visual acuity, best corrected visual acuity (BCVA), variation in intraocular pressure (IOP), anterior chamber depth (ACD), variation in endothelial cells, adverse events, and patient satisfaction. RESULTS: Nine patients had ICL implantation in 1 eye and 25 patients, in both eyes. Preoperatively, the spherical equivalent (SE) was between +2.75 diopters (D) and +11.75 D and astigmatism was between +0.50 D and +1.00 D. The mean SE of the manifest refraction was +0.07 +/- 0.54 D; refraction stabilized quickly and remained stable throughout the follow-up period. At 10 years, the safety index was 111 and the efficacy index, 96.8. Of the eyes, 86.5% had a change in SE refraction within +/-0.50 D; 1.6% lost 1 Snellen line of BCVA. The mean endothelial cell loss was 4.7%, which remained almost unchanged throughout the follow-up period. The mean variation in ACD was -14.9% and in IOP, +5.3%. CONCLUSIONS: The results confirmed the long-term safety, efficacy, accuracy, and predictability of ICL implantation for hyperopia. The Collamer material was well tolerated in all eyes. PMID- 17720074 TI - Postoperative course of intraocular pressure after cataract surgery with combined primary posterior capsulorhexis and posterior optic buttonholing. AB - PURPOSE: To evaluate the natural course of intraocular pressure (IOP) after cataract surgery with combined primary posterior continuous curvilinear capsulorhexis (PPCCC) and posterior optic buttonholing (POBH) of the intraocular lens (IOL) in adult patients. SETTING: Department of Ophthalmology, Medical University of Vienna, Vienna, Austria. METHODS: Fifty consecutive patients with age-related cataract awaiting cataract surgery under topical anesthesia in both eyes were enrolled prospectively. In randomized order, cataract surgery with combined PPCCC and POBH was performed in 1 eye. In the fellow eye, cataract surgery was performed conventionally with in-the-bag IOL implantation and the posterior lens capsule kept intact. Standardized IOP measurements by Goldmann applanation tonometry were performed 1, 2, 4, 6, 8, and 24 hours postoperatively. Follow-up IOP measurements were taken at 1 week and 1 month. Twenty-five patients received 1-time IOP-lowering medication immediately after cataract surgery; the other 25 did not receive IOP-lowering drops. RESULTS: During the first 24 hours postoperatively, no significant differences in IOP were observed between the PPCCC-POBH group and the conventional surgery group (P>.05). No IOP peaks greater than 27 mm Hg were observed in any eye. One week and 1 month postoperatively, no significant differences in IOP were found between groups (P>.05). The use of IOP lowering drops significantly reduced postoperative IOP. However, no IOP spikes >27 mm Hg were found with and without the use of IOP-lowering drops. CONCLUSION: The course of IOP after cataract surgery with combined PPCCC and POBH showed the technique to be as safe as conventional cataract surgery with in-the-bag IOL implantation. PMID- 17720075 TI - Deferral of first review after uneventful phacoemulsification cataract surgery until 2 weeks: randomized controlled study. AB - PURPOSE: To investigate the safety of deferring the ophthalmic review after uneventful phacoemulsification cataract surgery until 2 weeks after the procedure. SETTING: Waterford Regional Hospital, Waterford, Ireland. METHODS: After uneventful cataract surgery, 233 patients were randomized to have ophthalmic review 2 hours after the procedure and 2 weeks postoperatively (Group 1) or to forego any ophthalmic review before the 2-week postoperative visit in the outpatient department (Group 2). RESULTS: Of the 115 patients randomized to Group 1, 25 (21.7%) had intraocular pressure (IOP) spikes of 30 mm Hg or greater and 2 (1.7%) had a corneal abrasion in the immediate postoperative period. Group 1 and Group 2 were statistically similar in terms of problems encountered in the first 2 postoperative weeks and anterior segment findings and visual acuity at the 2-week postoperative visit. CONCLUSIONS: The results of this randomized controlled study indicate that the first ophthalmic review after uneventful cataract surgery can be safely deferred until 2 weeks postoperatively in patients in whom a transient IOP spike would not be deemed clinically deleterious. Such a policy will enhance the efficiency of day-surgery units. PMID- 17720076 TI - Anterior segment changes with age and during accommodation measured with partial coherence interferometry. AB - PURPOSE: To evaluate anterior segment alterations with age and during accommodation in different age groups. SETTING: Department of Ophthalmology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. METHODS: Fifty-three subjects (101 normal eyes) were enrolled in this study and divided into 3 age groups: younger than 30 years (Group 1), between 31 years and 44 years (Group 2), and older than 45 years (Group 3). The total amplitude of accommodation was determined with a defocusing technique, and anterior segment measurements were performed by partial coherence interferometry. RESULTS: Group 1 comprised 32 eyes; Group 2, 37 eyes; and Group 3, 32 eyes. The total amplitude of accommodation decreased with age (P<.0001). With the target position at infinity, the lens thickness (LT) and anterior segment length (ASL) increased and the anterior chamber depth (ACD) decreased significantly with age (P<.0001). During accommodation in the youngest group, the mean change in LT was 36.3 mum/diopter (D) and in ACD, -26.7 mum/D. The mean accommodation-induced ACD change was -0.08 mm +/- 0.06 (SD) in Group 1, -0.064 +/- 0.087 mm in Group 2, and -0.03 +/- 0.06 mm in Group 3 (P = .0004). The mean LT change during near fixation was 0.109 +/- 0.063 mm in Group 1, 0.103 +/- 0.136 mm in Group 2, and 0.006 +/- 0.05 mm in Group 3 (P<.0001). The mean ASL change during accommodation was 0.029 +/- 0.037 mm, 0.039 +/- 0.114 mm, and -0.023 +/- 0.051, respectively (P<.0001). CONCLUSIONS: In addition to forward movement of the anterior lens surface with age, the posterior surface moved backward. Alterations in LT and ACD sufficient for a unit of refractive power change during accommodation might be smaller than previously thought. Anterior shifting of the lens may also participate in the accommodative response. PMID- 17720077 TI - Importance of fundoscopy in refractive surgery. AB - PURPOSE: To examine the incidence, treatment, and outcomes of retinal lesions before and after refractive laser surgery. SETTING: Private refractive surgery practice. METHODS: A retrospective review was conducted of patients attending the laser clinic over a 3-year period. Examined were the incidence, type, management, and outcomes of the posterior segment abnormalities encountered. RESULTS: Fifty two (1.1%) of 4800 patients had posterior segment pathology requiring intervention. Forty-five cases (0.86%) were detected preoperatively and had a mean refraction of -4.5 diopters (D) +/- 3.0 (SD). Seven cases (0.14%) were detected postoperatively at a mean follow-up of 19 +/- 18.3 months; none had preoperative pathology. The mean refraction in this group was -4.4 +/- 2.3 D. Ninety-five percent had myopic prescriptions. All maintained best corrected visual acuity postoperatively. The incidence of retinal detachment was 0.03% per year in the myopic candidates; however, no cases occurred after the refractive procedure. CONCLUSION: Dilated fundus examination is an integral part of optimum clinical care in refractive patients, and shared preoperative assessment by a retinal specialist is advisable in those with predisposing retinal pathology. PMID- 17720078 TI - Laser-assisted corneal welding in cataract surgery: retrospective study. AB - PURPOSE: To evaluate the efficacy of laser welding to close corneal wounds in cataract surgery. SETTING: Department of Ophthalmology, Hospital of Misericordia e Dolce, Prato, Italy. METHODS: This retrospective nonrandomized interventional case series included 20 eyes of 20 patients. All eyes had cataract with visual acuity worse than 20/200. Ten patients had phacoemulsification surgery, and 10 had extracapsular cataract extraction (ECCE). Surgeries were followed by laser assisted closure of the corneal wounds by diode laser welding of the stroma using a technique established in animal models. Preoperative and postoperative (1, 3, 7, 30, and 90 days) astigmatism, level of inflammation, Seidel testing, and endothelial cell counts were obtained. RESULTS: There were minor differences in preoperative and postoperative astigmatism except in 1 eye in the ECCE group. The Seidel test showed no wound leakage during the follow-up examinations, and endothelial cell loss was similar to that published for standard surgical cataract procedures. No collateral effects of the laser welding were detected, nor was postoperative inflammation. CONCLUSIONS: Astigmatism was slightly affected by the use of laser welding for corneal wound closure after phacoemulsification and ECCE. The laser-assisted corneal sealing procedure was rapid and safe and could serve as an alternative to corneal suturing, with significant potential applications for the closure of longer incisions, such as those used in penetrating keratoplasty. PMID- 17720079 TI - Safety and efficacy of intraoperative intravitreal injection of triamcinolone acetonide injection after phacoemulsification in cases of uveitic cataract. AB - PURPOSE: To evaluate the safety and efficacy of a single intraoperative intravitreal injection of triamcinolone acetonide after phacoemulsification in patients with chronic idiopathic anterior uveitis or intermediate uveitis. SETTING: Dr. R.P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India. METHODS: This prospective randomized controlled study included 40 eyes (40 patients) with chronic idiopathic anterior uveitis or intermediate uveitis that had phacoemulsification with intraocular lens implantation. Twenty eyes received an intravitreal injection of triamcinolone acetonide (4 mg/0.1 mL) intraoperatively (triamcinolone acetonide group), and 20 received oral steroids (steroid group) postoperatively. Outcome measures were Early Treatment Diabetic Retinopathy Study best corrected visual acuity (BCVA), anterior chamber reaction, intraocular pressure (IOP) by applanation tonometry, and central macular thickness by optical coherence tomography. RESULTS: The mean BCVA (decimal) improved from a baseline of 0.13 +/- 0.14 to 0.64 +/- 0.32 in the triamcinolone acetonide group and from 0.05 +/- 0.06 to 0.61 +/- 0.36 in the steroid group (P = .74). There were no statistically significant differences between the 2 groups in postoperative anterior chamber reaction, IOP, or central macular thickness. Four patients in the triamcinolone acetonide group and 5 in the steroid group had recurrence of uveitis; 5 patients in the triamcinolone acetonide group had ocular hypertension. One patient in the triamcinolone acetonide group and 3 in the steroid group had cystoid macular edema postoperatively. CONCLUSION: A single intraoperative intravitreal injection of triamcinolone acetonide seemed to be a safe and efficacious route of steroid delivery during phacoemulsification in patients with chronic idiopathic anterior uveitis or intermediate uveitis and is recommended as a substitute for postoperative oral steroid administration. PMID- 17720081 TI - Intraocular lenses with surface aspherization: Interferometric study. AB - PURPOSE: To accurately evaluate in an optical laboratory 2 different types of intraocular lenses (IOLs). SETTING: Department of Oto-Neuro-Ophthalmological Surgical Sciences and CNR-Institute for Applied Optics, Florence Italy. METHODS: In this study, optical testing facilities based on interferometry were used. The IOLs were inspected with laser light, and interference patterns were acquired and processed, obtaining the physical parameters accounting for the lens behavior. Comparison of the respective performances within the pseudophakic eye was provided in terms of modulation transfer function (MTF) using lens diameters from 3.0 mm to 5.0 mm. The data were inserted in a mathematical model of the eye, and the relevant merit functions were computed with a ray-tracing program. RESULTS: Sample sets of both all-spherical IOLs and IOLs with aspherical surfaces were inspected. The interferometric maps showed clear evidence of the opposite wave aberration introduced by the different IOL types. With a 3.0 mm pupil diameter, both IOL types performed as almost ideal lenses, while with a 5.0 mm diameter, IOLs with aspherical surfaces effectively compensated for the spherical aberration of the cornea and had a significantly higher MTF. CONCLUSIONS: The interferometric approach to IOL testing provided accurate data on the physical parameters of the IOL. With a measuring and computing chain that includes eye modeling and ray tracing, it was possible to analyze in detail the process by which IOLs with aspherical surfaces compensate for the spherical aberration of the cornea under photopic, mesopic, and scotopic conditions. PMID- 17720080 TI - Safety of irrigation with 5-fluorouracil in a sealed-capsule irrigation device in the rabbit eye. AB - PURPOSE: To study the safety of irrigation with 5-fluorouracil (5-FU) in the Perfect Capsule sealed-capsule irrigation device (Milvella, Ltd., Epping, Australia). SETTING: St. Erik's Eye Hospital, Stockholm, Sweden. METHODS: Thirty 8-week-old rabbits were divided into 4 groups. Clear lens extraction was performed and the Perfect Capsule was applied in 1 eye in Groups 1, 2 and 3. The sealed system was flushed with balanced salt solution (BSS) in Group 1, 5-FU 50 mg/mL in Group 2, and 5-FU followed by BSS in Group 3. In Group 4, the Perfect Capsule was not applied; instead, 0.2 mL of 5-FU was instilled in the capsule and left there for 30 seconds. An endothelial cell count and pachymetry were performed preoperatively and 24 hours postoperatively. At 24 or 48 hours (half of each group at each time point), the rabbits were killed and the retina and trabecular meshwork histopathologically examined. The endothelial cell count and pachymetry were compared between the Perfect Capsule eye and the control eye in Group 1. RESULTS: There was no difference between the groups in endothelial cell count (P = .96) or pachymetry (P = .32). Histologic evaluation showed no damage from the 5-FU. The comparison between eyes in Group 1 showed that the use of the Perfect Capsule did not cause more endothelial cell loss (P = .86) or increase pachymetry more (P = .28) than in the control eye. CONCLUSION: Irrigation with 5 FU 50 mg/mL in the sealed-capsule irrigation device was safe and caused no apparent damage to the adjacent intraocular tissues. PMID- 17720082 TI - Role of the tear film in the optical quality of the human eye. AB - This paper reviews recent studies of the role of the tear film in the optical quality of the eye. Recent investigations focus on the dynamics of the tear film after a blink and its important role in the optical quality of the eye. The results in this review were used in an attempt to understand the optical and visual impact of tear-film breakup in normal eyes and dry eyes. It was noted that patients with dry-eye syndrome have large optical aberrations compared with those in normal eyes, which may be the cause of blurry vision associated with the syndrome. In addition, instillation of artificial tears reduces optical aberrations and thus improves the optical quality of vision in these patients. PMID- 17720084 TI - Bilateral deep anterior lamellar keratoplasty for the management of bilateral post-LASIK mycobacterial keratitis. AB - A 25-year-old Vietnamese man who had bilateral simultaneous laser in situ keratomileusis (LASIK) for moderate myopia developed bilateral Mycobacterium abscessus keratitis that was treated with intensive medical therapy, flap removal, superficial keratectomy, and, following disease progression, therapeutic deep anterior lamellar keratoplasty (DALK). To our knowledge, this is the first reported case of bilateral post-LASIK mycobacterial keratitis successfully treated with DALK. PMID- 17720083 TI - Multilayer amniotic membrane transplantation for bacterial keratitis with corneal perforation after hyperopic photorefractive keratectomy: case report and literature review. AB - We report a case of corneal infection caused by Streptococcus pneumoniae after hyperopic photorefractive keratectomy (PRK) that produced severe corneal melting, ulceration, and multiple perforations. Treatment included antibiogram-based antibiotic topical therapy and multilayer amniotic membrane transplantation (AMT) performed to seal the perforations and restore the globe integrity. Clinical and anterior segment optical coherence tomography (Visante OCT, Carl Zeiss Meditec) examinations documented progressive integration of the amniotic membrane tissues within the cornea, stromal and epithelial healing, and recovery of a stable and regular anterior chamber. The cornea healed with an avascular leucoma; the best corrected visual acuity was reduced to 20/200. Severe pneumococcal ulcerative perforation is a potential complication of PRK. Penetrating keratoplasty, at high risk for failure in the acute settings of an infected and inflamed eye, can be delayed until the cornea is healed. Amniotic membrane transplantation may be an alternative surgical option to achieve this goal. PMID- 17720085 TI - Corneal melting and perforation in Stevens Johnson syndrome following topical bromfenac use. AB - We report a case of a 20-year-old woman with tear deficiency secondary to Stevens Johnson syndrome who developed bilateral corneal melting following use of bromfenac (Xibrom), a nonsteroidal antiinflammatory drug (NSAID), for 2 weeks. The patient presented with complaints of light sensitivity and pain in the right eye. The slitlamp examination revealed a corneal perforation with iris plug in the right eye and an 85% thinned cornea in the left eye. She was admitted to the hospital, where Xibrom was discontinued, therapeutic contact lenses were placed, and a regimen of topical antibiotic agents was instituted. One day after admission, penetrating keratoplasty was performed in the right eye, an amniotic membrane was placed in the left eye, and tarsorrhaphy was performed bilaterally. The clinical features of this case highlight the importance of being selective when administering NSAIDs in patients with a compromised ocular surface. PMID- 17720086 TI - Management of exposure keratopathy associated with severe craniofacial trauma. AB - We describe a case of severe craniofacial trauma with resultant exposure keratopathy that was refractive to traditional treatment measures including aggressive lubrication, tarsorrhaphy, platinum lid weight implantation, punctal plugs, correction of lid retraction, amniotic membrane application, and multiple bandage contact lenses. Through combined Boston scleral lens placement and traumatic cataract extraction with intraocular lens (IOL) implantation using scleral lens IOL power calculations, we were able to maximize patient comfort and attain superior visual acuity. To our knowledge, calculation of IOL power through a scleral lens has not been described. PMID- 17720087 TI - Retrobulbar hemorrhage after sub-Tenon's anesthesia. AB - We present a case of retrobulbar hemorrhage complicating sub-Tenon's anesthesia in a patient receiving oral anticoagulants. To our knowledge, this has been described only once in the literature. PMID- 17720088 TI - Neuro-ophthalmic disorders presenting as a diagnostic surprise during pre-LASIK evaluation. AB - We present 2 cases that came to our institute for refractive surgery and were discovered to have serious systemic conditions requiring immediate intervention. On examination, prolactinoma of the pituitary gland was seen in one patient and multiple sclerosis was diagnosed in the other patient. Prompt treatment of the conditions led to improvement in the neuro-ophthalmic disorders. We recommend a thorough physical evaluation of patients having an ophthalmic examination. PMID- 17720089 TI - Cerulean posterior capsule opacity. AB - We present a case of light-blue posterior capsule opacification (PCO) in a patient who had cerulean cataracts removed 1 year earlier. The color of the PCO was similar to that of the cerulean cataracts prior to extraction. Posterior capsule opacification is a common complication after cataract surgery; however, we could not find a similar case of cerulean posterior capsule opacity in the literature. The findings in this case suggest that the mechanism of the light blue color formation in the cataract was also present in the lens epithelial cells forming the posterior capsule opacity. PMID- 17720090 TI - Rapidly progressing bilateral cataracts in a patient with beta thalassemia and pellagra. AB - Soon after the diagnosis of pellagra in a 20-year-old patient with beta thalassemia, bilateral intumescent cataracts rapidly developed. We believe the patient's crystalline lenses were at an increased oxidative state due to iron overload from the thalassemia. Depletion of the lens epithelial cells of an important antioxidative agent (glutathione) as a result of niacin (vitamin B3) deficiency due to pellagra reduced the antioxidative capacity of the lenses. The oxidative damage led to rapid development of cataracts. PMID- 17720091 TI - Acute angle-closure glaucoma due to iris transfixation of a subluxated posterior chamber intraocular lens-capsular bag complex. AB - An 80-year-old woman with pseudoexfoliation syndrome developed subluxation of a posterior chamber intraocular lens (IOL)-capsular bag complex due to zonular rupture. She underwent a limited 25-gauge pars plana vitrectomy and iris transfixation of the subluxated IOL-capsule complex. The postoperative course was uneventful until the patient developed acute angle-closure glaucoma 3 weeks postoperatively. Ultrasound biomicroscopy confirmed pupillary block by the IOL capsule complex. The patient was treated with intraocular pressure-lowering medications and a vitreous tap before a laser peripheral iridotomy could be performed successfully. The vision returned to normal, and the angle closure resolved. We recommend that a prophylactic surgical iridectomy be performed in patients with iris transfixation of a posterior chamber IOL-capsular bag complex. PMID- 17720092 TI - Cataract secondary to electrical shock from a Taser gun. AB - A 35-year-old man presented with traumatic iritis, angle-recession glaucoma, and a retinal dialysis secondary to blunt trauma from a Taser gun in the right eye and a unique electrical cataract in the left eye. Taser guns, which can also function as stun guns, can lead to electrical cataract formation. Given the increasing use of Taser guns by law enforcement and citizens, blunt mechanical and electrical sequelae of Taser gun injuries should be recognized. PMID- 17720093 TI - Choice of intraocular lens for pediatric cataract surgery: survey of AAPOS members. PMID- 17720094 TI - Significance of the expression of phosphorylated signal transducer and activator of transcription-3, -Akt, and -cyclin D1 in angiosarcoma. PMID- 17720096 TI - Can care bundles improve quality in emergency care? PMID- 17720097 TI - The history of the International Society of Renal Nutrition and Metabolism, 1977 2006. PMID- 17720098 TI - Gamma-tocopherol and docosahexaenoic acid decrease inflammation in dialysis patients. AB - OBJECTIVE: Increased cardiovascular risk in hemodialysis patients may be related to augmented oxidative stress and inflammation, for which no proven beneficial therapies are available. STUDY DESIGN: We examined the effects of gamma tocopherol and docosahexaenoic acid (DHA) administration on inflammation and oxidative stress markers in hemodialysis patients in a randomized, double blinded, placebo-controlled, clinical trial. Active treatment consisted of capsules containing gamma tocopherol (308 mg) and DHA (800 mg). SETTING: Outpatient dialysis center. PATIENTS: Seventy maintenance hemodialysis patients. MAIN OUTCOME MEASURES: Plasma concentrations of interleukin-6 (IL-6) and protein carbonyl content were determined by enzyme-linked immunosorbant assay. C-reactive protein was measured by nephelometry. The F(2) isoprostanes were measured by gas chromatography-mass spectrometry. Erythrocyte DHA content was measured by gas chromatography. RESULTS: Sixty-three patients were enrolled, and 57 completed the study. No serious adverse events were attributed to either active treatment or placebo. In the treatment group, but not in the placebo group, there were significant decreases in IL-6 (21.4 +/- 3.5 to 16.8 +/- 3.7 pg/mL), white blood cell (WBC) count (7.4 +/- 0.3 to 6.9 +/- 0.4 10(3)/microL), and neutrophil fraction of WBCs (4.8 +/- 0.3 to 4.4 +/- 0.3 10(3)/microL), at P < .05 for all. There were no significant changes in plasma concentrations of CRP, F(2) isoprostanes, or carbonyls in either group. CONCLUSION: Thus, gamma tocopherol and DHA are well-tolerated and reduce selected biomarkers of inflammation in hemodialysis patients. Larger randomized, clinical trials will be required to determine if gamma tocopherol and DHA can reduce cardiovascular complications in hemodialysis patients. PMID- 17720099 TI - Chronic kidney disease mineral bone disorder and health-related quality of life among incident end-stage renal-disease patients. AB - OBJECTIVE: Our objective was to determine the extent to which chronic kidney disease mineral bone disorder (CKD-MBD) is associated with health-related quality of life among incident dialysis patients. DESIGN: This study's design was a cross sectional analysis. SETTING: This was part of the United States Renal Data System Dialysis Morbidity and Mortality Study (DMMS), Wave 2. PATIENTS: The patients comprised 2590 adult participants in DMMS Wave 2, for whom quality of life and laboratory data were available. METHODS: We stratified patients according to their serum concentrations of phosphorus, calcium, and parathyroid hormone (PTH), and compared health-related quality of life as a function of these indicators in analyses adjusted for demographic, clinical, and other laboratory variables. MAIN OUTCOME MEASURES: Main outcome measures included Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, and the Symptom score of the Kidney Disease Quality of Life. RESULTS: Both high and low serum phosphorus concentrations were associated with lower PCS scores (-1.25 to -1.48 points compared with the reference category), as was low PTH (-1.49 points). Low serum phosphorus was associated with more severe symptoms of kidney disease (-3.88 points), but there were no associations between high phosphorus or either extreme of PTH and the Symptom score. Serum calcium concentration and the calcium x phosphorus product were unassociated with PCS or Symptom scores. There were no associations among phosphorus, calcium, or PTH and MCS. Analyses simultaneously controlling for serum phosphorus, calcium, and PTH showed similar results. CONCLUSION: High and low serum phosphorus and low PTH are associated with slightly poorer self-reported physical functioning. Clinical trials will be necessary to determine whether and to what extent improvement in health status may occur with the correction of selected disorders of mineral metabolism. PMID- 17720100 TI - Role of adipose tissue in determining muscle mass in patients with chronic kidney disease. AB - OBJECTIVE: Malnutrition is a powerful predictor of mortality in chronic kidney disease (CKD). However, its etiology is unclear. We hypothesized that the adipocyte-derived proteins leptin and adiponectin, inflammation (as measured by C reactive protein, CRP), and insulin resistance (as measured by homeostasis model assessment, HOMA), implicated in the malnutrition-inflammation complex syndrome commonly seen in maintenance dialysis patients, would be associated with the loss of muscle mass in earlier stages of CKD. Arm muscle area was used as an indicator of muscle mass. PATIENTS AND SETTING: The Modification of Diet in Renal Disease Study cohort of people with CKD stages 3 and 4 was used for analysis (N = 780). MAIN OUTCOME MEASURES: Regression models were carried out to examine the relationships of leptin, adiponectin, CRP, and HOMA with arm muscle area (the main study outcome). RESULTS: Arm muscle area was 39 +/- 15 cm(2) (mean +/- SD), and adiponectin levels were 13 +/- 7 microg/mL. Median and interquartile range (IQR) concentrations were: 9.0 (13.6) ng/mL for leptin, 2.3 (4.9) mg/L for CRP, and 2.4 (2.0) for HOMA. Higher leptin (beta coefficient and 95% confidence interval, -6.9 [-8.7 to -5.1], P < .001) and higher CRP (beta coefficient and 95% confidence interval, -2.7 [-3.9 to -1.4], P < .001) were associated with lower arm muscle area. There was a trend toward lower arm muscle area with higher adiponectin (P = .07), but no association with HOMA (P = .80). CONCLUSION: Leptin and CRP were associated with lower muscle mass in subjects with CKD at stages 3 and 4. Further studies are needed to understand the mechanisms underlying these associations, and to develop targeted interventions for this patient population. PMID- 17720101 TI - Knowledge of phosphorus compared with other nutrients in maintenance dialysis patients. AB - OBJECTIVE: This study's objective was to assess knowledge of phosphorus compared with other nutrients in patients undergoing maintenance dialysis (MD). DESIGN: We compared knowledge of phosphorus vs. other nutrients important to the MD diet (potassium, sodium, and protein) in patients undergoing hemodialysis (HD) and peritoneal dialysis (PD). We further measured gender, age, education level, and functional health literacy to assess correlations in patient nutrient knowledge. Nutrient knowledge was measured using a 25-item Chronic Kidney Disease Knowledge Assessment Tool for Nutrition (CKDKAT-N), and functional health literacy was measured using the short form of the Test of Functional Health Literacy in Adults (S-TOFHLA). SETTING AND PATIENTS: Patients received maintenance outpatient PD or HD at Wisconsin Dialysis, Inc. (Madison, WI). MAIN OUTCOME MEASURE: The main outcome measure was knowledge of phosphorus vs. knowledge of potassium, sodium, and protein. RESULTS: Forty-seven MD patients participated in the study (29 undergoing HD, 18 undergoing PD, 30 males, 17 females, average age of 58.6 (SD, 13.8) years, and average grade level of 1.4 (SD, 2.6) years of post-secondary education). Thirty-five participants had adequate health literacy, 4 had marginal health literacy, and 8 had inadequate health literacy. The CKDKAT-N scores ranged from 6-21 for 25 items, with a mean score of 13 (SD, 2.91). Knowledge of phosphorus compared with knowledge of other nutrients was poor (0.38 vs. 0.72, P = .003). In a comparison of HD vs. PD patient knowledge, both phosphorus (0.37 vs. 0.42, P = .231) and other nutrients (0.69 vs. 0.80, P = .115) were the same. CONCLUSION: Despite regular dietary instruction, patients undergoing MD have a poor knowledge of dietary phosphorus content, compared with knowledge of other nutrients important in chronic kidney disease. Interestingly, there was no difference in nutrition knowledge when comparing PD and HD patients, despite differences in education level and health literacy between groups. PMID- 17720102 TI - Continuous ambulatory peritoneal dialysis patients are unable to increase dietary intake to recommended levels. AB - OBJECTIVE: This study's objective was to determine whether offering dietary advice was effective in supporting patients in adjusting energy intake. DESIGN: We performed a prospective, randomized, controlled trial of dietary intervention involving 59 patients on continuous ambulatory peritoneal dialysis over a 4-month follow-up period. SETTING: The study involved outpatients on home-based renal replacement therapy. PARTICIPANTS: All participants were adult patients on continuous ambulatory peritoneal dialysis. All eligible patients were invited to take part. Subjects were randomized into two groups: control and intervention. Those with diabetes mellitus, malabsorption, malignancy, or eating disorders were excluded. INTERVENTION: Baseline measurements to assess current dietary intake and nutritional status were performed in all subjects. Measurements included a 5 day food diary, subjective global assessment (SGA), anthropometry, and serum biochemistry. After analysis of the food diaries, the participants in the control group were given follow-up dietary advice that would enable them to match intake with current dietary recommendations for this group of 1.2 g of protein per kilogram of ideal body weight, 25 cal/kg ideal body weight. Participants in the intervention group were given follow-up dietary advice that would encourage them to match energy intake with an estimate of total energy expenditure based on their calculated basal metabolic rate and physical activity level as designated using information from SGA, with a significantly lower protein intake of 0.8 to 1.0 g/kg ideal body weight and an emphasis on calories from carbohydrate and fat. Both groups completed further 5-day food diaries at 2 and 4 months to assess their ability to make the recommended changes. SGA, anthropometry, and biochemistry were all remeasured at the end of the study period. MAIN OUTCOME MEASURE: Differences in energy and protein intakes between and within the two groups from baseline to 4 months were assessed. RESULTS: Protein and energy intakes did not change during 4 months in either group, and there was no significant difference in intake between the two groups. In the control group (n = 27), 18 subjects (69%) matched their reported dietary energy intake to the recommended intake. In the intervention group (n = 28), 17 subjects (63%) matched their reported dietary intake to their estimated total energy expenditure. In the control group (n = 27), 8 subjects (28%) achieved the protein intake recommended to them of 1.2 g/kg. In the intervention group (n = 28), 23 subjects (85%) achieved the protein intake recommended to them of greater than 0.8 g/kg. CONCLUSION: Patients not meeting their dietary prescription did not adjust their intake to match the recommended advice they had been given from a dietitian. Food diary analysis showed that subjects ate less than the recommended intakes for energy and protein. This inability to change suggests that subjects may be eating to the limit of their appetite. SGA sections concerning appetite, body weight, body mass index, and estimates of energy expenditure support the view that energy intake matches requirements. PMID- 17720103 TI - Multicenter study of the validity and reliability of subjective global assessment in the hemodialysis population. AB - OBJECTIVE: Subjective Global Assessment (SGA) is a nutrition assessment tool recommended by the 2000 NKF K/DOQI Nutrition Guidelines. However, the validity and reliability of this tool have not been established in hemodialysis (HD) patients. The purpose of this observational study was to determine the reliability and validity of SGA in the HD population. Renal dietitians (RD) were recruited to perform SGA (7-point scale version) and collect data on demographics, clinical status, biochemistries, dietary intake, and quality of life (Medical Outcomes Short Form-36) on 3 HD patients at baseline and 6 months later. DESIGN: The 54 participating RDs were trained to perform SGA and collect data via a website created for this study. Interrater reliability for SGA was tested in a subset of 76 patients, via an SGA performed by a second RD at baseline, while intrarater reliability was assessed by the original RD repeating the SGA at 1 month. Data collection occurred at HD facilities in the United States (109 patients), Canada (35 patients), and New Zealand (9 patients). RESULTS: Of the 153 patients, 46% were female, 64% were Caucasian, 6% were Hispanic, 21% were African American, and 6% were Asian. The primary etiologies were hypertension (33%), type 2 diabetes mellitus (DM) (27%), type 1 DM (10%), and glomerular nephritis (10%); 59% had cardiovascular disease. The mean age, body mass index (BMI), serum albumin, and duration on HD were 64 +/- 14 years (mean +/- SD), 28 +/- 7 kg/m(2), 3.7 +/- 0.4 mg/dL, and 41 +/- 34 months, respectively. SGA scores were well nourished (7)-30%; mildly malnourished (MN 6) 41%; moderately MN 5-21%, 4-7%, and 3-2%; and severely MN (2 and 1)-0%. SGA training via the Internet achieved fair interrater reliability (weighted Kappa = 0.5, Spearman's Rho = 0.7) and substantial intrarater reliability (weighted Kappa = 0.7, Spearman's Rho = 0.8) (P < .001). Validity was demonstrated through statistically significant differences in mean BMI and serum albumin across the 5 categories of SGA (7-28 +/- 7, 6-29 +/- 7, 5-28 +/- 8, 4-21 +/- 4, 3-24 +/- 2, P < .05; and 7-3.8 +/- 0.3, 6-3.8 +/- 0.4, 5-37 +/- 0.05, 4-3.4 +/- 0.07, 3-2.9 +/- 1.2, P < .001, respectively). Nutritional status varied by age (P < .05), but not ethnicity or nationality. CONCLUSION: We conclude that the 7-point scale SGA is a reliable and valid tool for nutritional assessment in adults on HD. PMID- 17720104 TI - Serum levels of folate and cobalamin are lower in depressed than in nondepressed hemodialysis subjects. AB - OBJECTIVE: The purpose of this study was to evaluate if there was a significant difference in serum and RBC folate or serum cobalamin levels in depressed and nondepressed subjects on hemodialysis (HD). DESIGN: A cross-sectional design was used in this study. Each subject's serum folate and cobalamin, and red blood cell (RBC) folate were measured. The Beck Depression Index II (BDI-II) was used to assess for depression. Subjects with scores of 10 or greater were considered depressed. Other laboratory, anthropometric, and demographic data were obtained from the subjects' medical records. To assess for significant differences (P < 0.05) in the laboratory values of the outcome variables between depressed and nondepressed subjects, t tests were performed on the groups' mean values. SETTING: The study was conducted with patients in two dialysis centers in Texas. PATIENTS OR OTHER PARTICIPANTS: Seventy-three individuals undergoing HD for at least six months who met study inclusion criteria were solicited to participate in the study after the study was approved by the respective institutional review board. INTERVENTION: Depression and mental status of each subject were assessed using the BDI-II and the Folstein Mini-Mental State Exam, respectively. MAIN OUTCOME MEASURE: Serum folate, cobalamin, total homocysteine, and RBC folate were measured and mean values were evaluated for significant differences in the depressed and nondepressed groups. RESULTS: Of the subjects in this study, 43.8% had BDI-II scores > 10 indicating depression. The nondepressed subjects had significantly higher mean serum folate (281 +/- 649 vs. 52 +/- 137 ng/mL), serum cobalamin (1162 +/- 1014 vs. 757 +/- 463 pg/mL), and RBC folate (1433 +/- 1757 vs. 810 +/- 654 ng/mL) levels than did depressed subjects. In the nondepressed group, 39% of subjects were taking a supplement containing 35-42 mg folacin and 7 mg cobalamin per week while only 9.1% of depressed subjects were taking a vitamin containing these levels of B vitamins. The group means were not significantly different for age, months on HD, body mass index, erythropoietin/kg body weight, total homocysteine, hemoglobin, albumin, or ferritin. CONCLUSION: As with the general population, lower serum folate, RBC folate, and serum cobalamin levels were found in depressed as compared to nondepressed subjects on HD. Plasma levels of these vitamins may be one of many factors related to depression, but larger studies with stronger designs are needed to confirm the results of this study. PMID- 17720105 TI - Phosphorus-containing food additives and the accuracy of nutrient databases: implications for renal patients. AB - OBJECTIVE: Phosphorus-containing additives are increasingly being added to food products. We sought to determine the potential impact of these additives. We focused on chicken products as an example. METHODS: We purchased a variety of chicken products, prepared them according to package directions, and performed laboratory analyses to determine their actual phosphorus content. We used ESHA Food Processor SQL Software (version 9.8, ESHA Research, Salem, OR) to determine the expected phosphorus content of each product. RESULTS: Of 38 chicken products, 35 (92%) had phosphorus-containing additives listed among their ingredients. For every category of chicken products containing additives, the actual phosphorus content was greater than the content expected from nutrient database. For example, actual phosphorus content exceeded expected phosphorus content by an average of 84 mg/100 g for breaded breast strips. There was also a great deal of variation within each category. For example, the difference between actual and expected phosphorus content ranged from 59-165 mg/100 g for breast patties. Two 100-g servings of additive-containing products contained, on average, 440 mg of phosphorus, or about half the total daily recommended intake for dialysis patients. CONCLUSIONS: Phosphorus-containing additives significantly increase the amount of phosphorus in chicken products. Available nutrient databases do not reflect this higher phosphorus content, and the variation between similar products makes it impossible for patients and dietitians to accurately estimate phosphorus content. We recommend that dialysis patients limit their intake of additive-containing products, and that the phosphorus content of food products be included on nutrition facts labels. PMID- 17720106 TI - Notes from the CKD kitchen: restaurant dining. AB - As a chronic kidney disease patient, have you wondered how to dine in a variety of restaurants guilt-free? I have received many questions on this subject lately, which inspired me to share my strategies for a successful dining experience using my culinary knowledge. I always try to call the restaurant ahead of time and explain to them my dietary guidelines and the reason for these guidelines. If I'm not able to give the restaurant any advance notice, I follow four simple steps once I arrive at that restaurant to create a wonderful meal that will follow my doctor's and dietitian's nutritional guidelines. PMID- 17720107 TI - Chinese nutrition educational materials for renal patients. AB - Nutrition resources in Chinese have been developed for the patients in St. Paul's Hospital's Renal Program. The goal was to support this patient subgroup to understand and practice the complicated diet guidelines within their own language and cultural contexts. PMID- 17720108 TI - Research: be part of the solution. PMID- 17720109 TI - Mandating two-year regional anesthesia fellowships: fanning the academic flame or extinguishing it? PMID- 17720110 TI - Close counts. PMID- 17720111 TI - Efficacy of continuous femoral nerve block with stimulating catheters versus nonstimulating catheters for anterior cruciate ligament reconstruction. AB - BACKGROUND AND OBJECTIVES: This prospective randomized controlled trial investigated the clinical efficacy of stimulating catheters for continuous femoral nerve block in patients who underwent anterior cruciate ligament reconstruction. METHODS: Seventy patients were randomized to either a stimulating catheter (SC, n = 35) or a nonstimulating catheter (NSC, n = 35) for femoral nerve block using 25 mL ropivacaine 7.5 mg/mL and clonidine 50 microg injected through the catheter. A single-injection sciatic block was also given to ensure surgical anesthesia. The time to loss of sensation to cold and pinprick of the femoral nerve was registered as the onset time. Data were registered intra- and postoperatively regarding pain scores, adverse effects, and need for supplemental anesthesia and analgesia other than a continuous postoperative infusion of ropivacaine 2 mg/mL through the continuous femoral nerve catheter set at 7 mL/h. RESULTS: Onset time was faster in the SC group (SC: 6.4 +/- 2.5, NSC: 8.3 +/- 2.9 min, P = .006). Visual analog scale pain scores were similar in both groups. The number of patient-controlled regional analgesia boluses (SC: 14.6 +/- 12.6, NSC: 23.2 +/- 13.6 mg ropivacaine 2 mg/mL, P = .008) as well as intravenous rescue ketorolac (SC: 34.3 +/- 35.7, NSC: 54 +/- 39.7 mg, P = .033) administered were higher in the NSC group. CONCLUSION: Although the use of a stimulating catheter was associated with faster onset time for the femoral nerve block and lower additional analgesics postoperatively, the clinical superiority (analgesia; lateral femoral cutaneous, and obturator nerve block) of stimulating catheters was not evident in this clinical setting. PMID- 17720112 TI - Magnesium sulfate diminishes the effects of amide local anesthetics in rat sciatic-nerve block. AB - BACKGROUND AND OBJECTIVES: Magnesium sulfate (MgSO(4)) is well known as an antagonist of N-methyl-d-aspartate receptors and was used for intrathecal analgesia a century ago. However, the effects of MgSO(4) combined with local anesthetics (LAs) on peripheral nerves are unclear. We tested the hypothesis that MgSO(4) could be used as an adjuvant to prolong and intensify conduction block by amide-type LAs in a rat sciatic-nerve block model. Further, the mechanism of possible synergy between LAs and MgSO(4) was investigated in whole-cell mode patch-clamp experiments. METHODS: Sciatic nerves were exposed to 2%/73.9 mM lidocaine, 0.25%/7.7 mM bupivacaine, and 0.5%/15.4 mM ropivacaine, with or without addition of 1.25%, 2.5%, or 5% MgSO(4)/50.7 mM, and nerve block characteristics were assessed. To elucidate the LA-MgSO(4) interaction, voltage dependent inactivation curves were determined in cultured rat GH(3) cells that expressed neuronal Na(+) channels. RESULTS: Unexpectedly, the addition of MgSO(4) overall significantly shortened the duration of block by lidocaine, bupivacaine, and ropivacaine. The steady-state inactivation of Na(+) channels in the presence of 300 muM lidocaine was almost unchanged by the addition of 10 mM MgSO(4), indicating that MgSO(4) does not affect the potency of lidocaine toward the inactivated Na(+) channel. CONCLUSIONS: MgSO(4) coadministered with amide-type LAs shortened the duration of sciatic-nerve block in rats. Therefore, it does not seem to be useful as an adjuvant for peripheral-nerve block. The mechanism of this observed antagonism is unclear but appears to be independent of the action of LAs and MgSO(4) at the LA receptor within the Na(+) channel. PMID- 17720113 TI - Preliminary evaluation of infraclavicular catheters inserted using ultrasound guidance: through-the-catheter anesthesia is not inferior to through-the-needle blocks. AB - BACKGROUND AND OBJECTIVES: This prospective study compared the initial block quality and surgical anesthesia rates of ultrasound-guided infraclavicular blocks with local-anesthetic injected through a catheter versus through a needle. We hypothesized that positioning of the catheter immediately posterior to the axillary artery would produce through-the-catheter (TTC) anesthesia with rates of complete block not inferior to through-the-needle (TTN) injection. METHODS: Eighty patients undergoing hand or forearm surgery extensive enough to require regional anesthesia were randomized into 2 groups of 40. In group TTN, local anesthetic was deposited posterior, lateral, and medial to the axillary artery using as few injections as necessary. In group TTC, a 20-gauge, multiorifice catheter was positioned between the posterior wall of the axillary artery and the posterior cord of the brachial plexus. All blocks were performed by use of ultrasound visualization with a 6-MHz to 10-MHz 38-mm linear probe. Local anesthetic solution consisted of 0.5 mL/kg lidocaine 2% with epinephrine. Sensory and motor blocks, as well as supplementation rates, were evaluated for the musculocutaneous, median, radial, and ulnar nerves. RESULTS: Complete sensory block of all nerve territories was achieved in 92% of patients in group TTN and 90% in group TTC (P = .51). In group TTN, 90% of patients had satisfactory anesthesia for surgery (no discomfort and no need for anesthetic supplementation of any type) compared with 92% in group TTC (P = .51). CONCLUSION: Ultrasound guided TTC infraclavicular block produced perioperative anesthesia that was not inferior to a TTN technique. PMID- 17720115 TI - Hemodynamic effects of thoracic epidural analgesia in ovine hyperdynamic endotoxemia. AB - BACKGROUND AND OBJECTIVES: Thoracic epidural analgesia (TEA) is increasingly used for perioperative analgesia. If patients with TEA develop sepsis or systemic inflammatory response subsequent to extended surgery the question arises if it would be safe to continue TEA with its beneficial effects of improving gastrointestinal perfusion and augmenting tissue oxygenation. A major concern in this regard is hemodynamic instability that might ensue from TEA-induced vasodilation. The objective of the present study was to assess the effects of TEA on systemic and pulmonary hemodynamics in a sepsis model of hyperdynamic endotoxemia. METHODS: After a baseline measurement in healthy sheep (n = 14), Salmonella thyphosa endotoxin was continuously infused at a rate of 10 ngxkg( 1)xmin(-1) over 16 hours. The surviving animals (n = 12) were then randomly assigned to 1 of 2 study groups. In the treatment group (n = 6), continuous TEA was initiated with 0.1 mLxkg(-1) bupivacaine 0.125% and maintained with 0.1 mLxkg(-1)xh(-1). In the control group (n = 6) the same amount of isotonic sodium saline solution was injected at the same rate through the epidural catheter. RESULTS: In both experimental groups cardiac index increased and systemic vascular resistance decreased concurrently (each P < .05). Functional epidural blockade in the TEA group was confirmed by sustained suppression of the cutaneous (or panniculus) reflex. During the observational period of 6 hours neither systemic nor pulmonary circulatory variables were impaired by TEA. CONCLUSIONS: From a hemodynamic point of view, TEA presents as a safe treatment option in sepsis or systemic inflammatory response syndrome. PMID- 17720114 TI - Dyloject, a novel injectable diclofenac formulation, offers greater safety and efficacy than voltarol for postoperative dental pain. AB - BACKGROUND AND OBJECTIVES: Voltarol for injection (a diclofenac sodium formulation employing polyethylene glycol and benzyl alcohol [PG-BA] as excipients) is marketed in Europe but not in North America. A suspension, PG-BA diclofenac sodium, requires preparation for each patient and slow IV infusion to minimize venous irritation. Dyloject, a novel diclofenac formulation, employs hydroxypropyl beta-cyclodextrin (HPbetaCD) to solubilize diclofenac in a small volume. We compared the efficacy and safety of an IV HPbetaCD diclofenac sodium bolus, a 30-minute PG-BA diclofenac sodium infusion, and placebo in post-molar extraction pain. METHODS: A total of 155 adult patients were randomized to receive HPbetaCD diclofenac sodium 75 mg, PG-BA diclofenac sodium 75 mg, or placebo. Primary endpoints were superiority of HPbetaCD diclofenac sodium to placebo and noninferiority of HPbetaCD diclofenac sodium to PG-BA diclofenac sodium with respect to total pain relief over 4 hours (TOTPAR4) on a 0 to 100-mm visual analog scale (VAS). Secondary endpoints included categorical TOTPAR4, VAS and categorical TOTPAR up to 8 hours, other measures of pain intensity and relief, patient global evaluation, and time to rescue medication. RESULTS: HPbetaCD diclofenac sodium had efficacy superior to both placebo and PG-BA diclofenac sodium. At 15 minutes, more patients given HPbetaCD diclofenac sodium than PG-BA diclofenac sodium reported 30% reduction in pain intensity (52% vs. 21%, P = .0022). Both diclofenac products had a 6-hour duration of effect and were well tolerated. Patient global evaluations of HPbetaCD diclofenac sodium were high, superior to placebo, and similar to PG-BA diclofenac sodium. The adverse event (AE) incidence was similar for HPbetaCD diclofenac sodium and PG-BA diclofenac sodium, except that in the current trial and in integrated safety results from the present and prior studies, phlebitis was more common with PG-BA diclofenac sodium. No cardiac or renal AEs or gastrointestinal bleeding were reported or observed. CONCLUSIONS: IV bolus HPbetaCD diclofenac sodium produced analgesia more quickly than, and with equal duration as, the 30-minute PG-BA diclofenac sodium infusion. Pooled data on thrombophlebitis from the present investigation and our prior studies of the novel formulation indicate this adverse effect is less frequent and less severe with HPbetaCD diclofenac sodium than with PG-BA diclofenac sodium. PMID- 17720116 TI - Ultrasound-guided versus computed tomography-controlled facet joint injections in the lumbar spine: a prospective randomized clinical trial. AB - BACKGROUND AND OBJECTIVES: Facet joint injections are widely used for alleviation of back pain. Injections are preferentially performed as fluoroscopy or computed tomography (CT)-controlled interventions. Ultrasound provides real-time monitoring, does not produce ionizing radiation, and is broadly available. METHODS: We studied feasibility, accuracy, time-savings, radiation doses, and pain relief of ultrasound-guided facet joint injections versus CT-controlled interventions in a prospective randomized clinical trial. Forty adult patients with chronic low back pain were consecutively enrolled and evenly assigned to an ultrasound or a CT- group. RESULTS: Eighteen subjects from the group randomized to ultrasound were judged to be feasible for this type of approach. In 16 of them the facet joints were clearly visible and all of the associated facet joint injections were performed correctly. The duration of procedure and radiation dose was 14.3 +/- 6.6 minutes and 14.2 +/- 11.7 mGy.cm in the ultrasound group, and 22.3 +/- 6.3 minutes and 364.4 +/- 213.7 mGy.cm in the CT group. Both groups showed a benefit from facet joint injections. CONCLUSIONS: The ultrasound approach to the facet joints in the lumbar spine is feasible with minimal risks in a large majority of patients and results in a significant reduction of procedure duration and radiation dose. PMID- 17720117 TI - Motor blocking minimum local anesthetic concentrations of bupivacaine, levobupivacaine, and ropivacaine in labor. AB - BACKGROUND AND OBJECTIVES: Adequate comparison of blocking capabilities of local anesthetics should be done with some knowledge of their relative potencies. The objective of this clinical trial was to simultaneously determine the motor blocking minimum local anesthetic concentrations (MMLAC) and the relative potency ratios for racemic bupivacaine, levobupivacaine, and ropivacaine during labor. METHODS: We studied parturients with singleton term pregnancies in vertex presentation. Each patient received a 20 mL epidural bolus of bupivacaine, levobupivacaine, or ropivacaine determined by the MMLAC model. Baseline and 30 min after injection, measurements of pain and muscle strength were performed, with assessment of motor strength in the legs at 30 min being the primary outcome measure. RESULTS: There were no differences in demographic, hemodynamic, or obstetric characteristics between the patients receiving the three local anesthetics. The estimated MMLAC with the 95% confidence intervals (CI) were: Bupivacaine: 0.26% wt/vol (0.22-0.30); Levobupivacaine: 0.30% wt/vol (0.25-0.36); Ropivacaine: 0.34% wt/vol (0.29-0.38). ANOVA of MMLAC estimates was significant (F = 3.32, P = .046), and when ranked by analgesic potencies, a significant linear trend (P = .014) to increasing motor blocking potencies from ropivacaine to levobupivacaine to bupivacaine was also found. CONCLUSIONS: This study confirms a motor blocking hierarchy for the three pipecoloxylidines. PMID- 17720119 TI - Dag E. Selander, M.D., PH.D.: Labat lecturer 2006. PMID- 17720118 TI - Should we add clonidine to local anesthetic for peripheral nerve blockade? A qualitative systematic review of the literature. AB - BACKGROUND AND OBJECTIVES: Although clonidine has been shown to prolong analgesia in central neuraxial blocks, its use in peripheral nerve blocks remains controversial. We performed a systematic review of the current literature to determine the benefit of adding clonidine to peripheral nerve blocks. METHODS: A systematic, qualitative review of double-blind randomized controlled trials on the benefit of clonidine as an adjunct to peripheral nerve block was performed. Studies were identified by searching PubMed (www.ncbi.nlm.nih.gov/entrez) and EMBASE (www.embase.com) databases (July 1991 to October 2006) for terms related to clonidine as an adjunct to peripheral nerve blocks. Studies were classified as supportive if the use of clonidine demonstrated reduced pain and total analgesic consumption, or prolonged block duration versus negative if no difference was found. RESULTS: Twenty-seven studies were identified that met the inclusion criteria. Five studies included a systemic control group. The total number of patients reviewed was 1,385. The dose of clonidine varied from 30 to 300 mug. Overall 15 studies supported the use of clonidine as an adjunct to peripheral nerve blocks with 12 studies failing to show a benefit. Based on qualitative analysis, clonidine appeared to prolong analgesia when added to intermediate acting local anesthetics for axillary and peribulbar blocks. CONCLUSIONS: Clonidine improves duration of analgesia and anesthesia when used as an adjunct to intermediate-acting local anesthetics for some peripheral nerve blocks. Side effects appear to be limited at doses up to 150 mug. Evidence is lacking for the use of clonidine as an adjunct to local anesthetics for continuous catheter techniques. Further research is required to examine the peripheral analgesic mechanism of clonidine. PMID- 17720120 TI - Labat lecture 2006. Regional anesthesia: aspects, thoughts, and some honest ethics; about needle bevels and nerve lesions, and back pain after spinal anesthesia. PMID- 17720121 TI - Anatomical location of the bifurcation of the sciatic nerve in the posterior thigh in infants and children: a formula derived from MRI imaging for nerve localization. AB - BACKGROUND AND OBJECTIVES: Sciatic nerve block is performed at the popliteal fossa for various surgical procedures in infants and children. The aim of this study is to review magnetic resonance imaging scans in children of various ages to assess the location of the division of the nerve in the posterior thigh. METHODS: After Institutional Review Board approval was obtained, measurements of the bifurcation of the sciatic nerve in the posterior thigh were recorded from magnetic resonance images that were previously obtained in children of various ages. Data were recorded in a database and parametric and nonparametric statistical analysis was performed. RESULTS: Measurements were recorded from 59 patient images. Using a linear regression model, we were able to arrive at a formula for determining the point of bifurcation of the sciatic nerve at the posterior thigh. The mathematical formula derived from the linear regression equation was: CONCLUSIONS: We speculate that this knowledge will assist practitioners who use nerve stimulation techniques for sciatic nerve blocks in children of all ages. PMID- 17720122 TI - Uneventful removal of an epidural catheter guided by impedance aggregometry in a patient with recent coronary stenting and treated with clopidogrel and acetylsalicylic acid. AB - OBJECTIVE: This report suggests that impedance aggregometry can be helpful to assess optimum time for and minimize the risk of catheter removal during double antiplatelet therapy. CASE REPORT: A 52-year-old patient undergoing cystectomy during combined general and epidural anesthesia suffered an acute myocardial infarction, and required coronary artery stenting and dual antiplatelet function therapy. CONCLUSIONS: Balancing the risks of stent occlusion and epidural bleeding, bedside impedance aggregometry helped to identify the optimum time window for epidural catheter removal with the lowest bleeding risk in this patient. PMID- 17720124 TI - Ultrasound and transcutaneous neurostimulator combined technique as a training method for nerve identification in anesthesia residents. PMID- 17720123 TI - Local opioid analgesia at cervical sympathetic Ganglia: what is the contribution of placebo effect? PMID- 17720125 TI - Common sense asepsis. PMID- 17720126 TI - Paramedial approach to the ganglion impar. PMID- 17720127 TI - Hydrodynamics of the spinal epidural space. PMID- 17720128 TI - Perineural space versus nerve's perineurium-beware the latter are potential expressways to the spinal cord! PMID- 17720129 TI - Sonography for saphenous nerve block near the adductor canal. PMID- 17720130 TI - Ultrasound assisted perineural catheter placement facilitated by a catheter introduction syringe. PMID- 17720131 TI - Highly sensitive and selective method to detect dopamine in the presence of ascorbic acid by a new polymeric composite film. AB - A new approach was applied to modify gold electrode with a unique polymer composite for selectively detecting dopamine (DA), a neurotransmitter, in the presence of an electroactive species of ascorbic acid (AA). After self-assembly of 11-mercaptoundecanoic acid (MUA) monolayer on gold surface, polyethylene glycol (PEG) was used to perform electrochemical esterification with MUA. In general, AA is the main interference of DA detection in a biological system. The resulting composite layer showed high sensitivity to detect DA but selectively blocked the interference from AA. Furthermore, for the first time, an interesting mechanism was demonstrated from our experimental results, namely, that the catalytic effect of AA on DA is limited by DA concentration when AA/DA>1. The modified electrode showed good reproducibility (+/-2% relative standard deviation), a low detection limit (10 nM), a fast response time (<2s), high sensitivity (86 nA/microM), a wide dynamic range of detection (20 microM), and great selectivity (without AA interference). The discovery is very promising for applications of detection of DA in a physiological environment where a high concentration of AA always exists. PMID- 17720132 TI - "Twitchin-actin linkage hypothesis" for the catch mechanism in molluscan muscles: evidence that twitchin interacts with myosin, myorod, and paramyosin core and affects properties of actomyosin. AB - "Twitchin-actin linkage hypothesis" for the catch mechanism in molluscan smooth muscles postulates in vivo existence of twitchin links between thin and thick filaments that arise in a phosphorylation-dependent manner [N.S. Shelud'ko, G.G. Matusovskaya, T.V. Permyakova, O.S. Matusovsky, Arch. Biochem. Biophys. 432 (2004) 269-277]. In this paper, we proposed a scheme for a possible catch mechanism involving twitchin links and regulated thin filaments. The experimental evidence in support of the scheme is provided. It was found that twitchin can interact not only with mussel myosin and rabbit F-actin but also with the paramyosin core of thick filaments, myorod, mussel thin filaments, "natural" F actin from mussel, and skeletal myosin from rabbit. No difference was revealed in binding of twitchin with mussel and rabbit myosin. The capability of twitchin to interact with all thick filament proteins suggests that putative twitchin links can be attached to any site of thick filaments. Addition of twitchin to a mixture of actin and paramyosin filaments, or to a mixture of Ca(2+)-regulated actin and myosin filaments under relaxing conditions caused in both cases similar changes in the optical properties of suspensions, indicating an interaction and aggregation of the filaments. The interaction of actin and myosin filaments in the presence of twitchin under relaxing conditions was not accompanied by an appreciable increase in the MgATPase activity. We suggest that in both cases aggregation of filaments was caused by formation of twitchin links between the filaments. We also demonstrate that native thin filaments from the catch muscle of the mussel Crenomytilus grayanus are Ca(2+)-regulated. Twitchin inhibits the ability of thin filaments to activate myosin MgATPase in the presence of Ca(2+). We suggest that twitchin inhibition of the actin-myosin interaction is due to twitchin-induced switching of the thin filaments to the inactive state. PMID- 17720133 TI - ATP modulation of mitogen activated protein kinases and intracellular Ca2+ in breast cancer (MCF-7) cells. AB - In the breast tumor cell line MCF-7, extracellular nucleotides induce transient elevations in intracellular calcium concentration ([Ca(2+)](i)). In this study we show that stimulation with ATP or UTP sensitizes MCF-7 cells to mechanical stress leading to an additional transient Ca(2+) influx. ATP> or =ATPgamma-S> or =UTP>>>ADP=ADPbeta-S elevate [Ca(2+)](i), proving the presence of P2Y(2)/P2Y(4) purinergic receptor subtypes. In addition, cell stimulation with ATP, ATPgamma-S or UTP but not ADPbeta-S induced the phosphorylation of ERK1/2, p38 and JNK1/2 mitogen activated protein kinases (MAPKs). The use of Gd(3+), La(3+) or a Ca(2+) free medium, inhibited ATP-dependent stress activated Ca(2+) (SAC) influx, but had no effect on MAPK phosphorylation. ATP-induced activation of MAPKs was diminished by two PI-PLC inhibitors and an IP(3) receptor antagonist. These results evidence an ATP-sensitive SAC influx in MCF-7 cells and indicate that phosphorylation of MAPKs by ATP is dependent on PI-PLC/IP(3)/Ca(2+)(i) release but independent of SAC influx in these cells, differently to other cell types. PMID- 17720134 TI - Entropy production and the Second Law in photosynthesis. AB - An assertion that the primary photochemistry of photosynthesis can violate the Second Law of thermodynamics in certain efficient systems has been put forward by Jennings et al., who maintain their position strongly despite an argument to the contrary by Lavergne. We identify a specific omission in the calculation of Jennings et al. and show that no violation of the Second Law occurs, regardless of the photosynthetic efficiency. PMID- 17720135 TI - Marcus treatment of endergonic reactions: a commentary. AB - Two forms of the equation for expression of the rate constant for electron transfer through a Marcus-type treatment are discussed. In the first (exergonic) form, the Arrhenius exponential term was replaced by its classical Marcus term; in the second (endergonic) form, the forward rate constant was replaced by the reverse rate constant (the forward rate constant in the exergonic direction), which was expanded to an equivalent Marcus term and multiplied by the equilibrium constant. When the classical Marcus treatment was used, these two forms of the rate equation give identical curves relating the logarithm of the rate constant to the driving force. The Marcus term for the relation between activation free energy, DeltaG#, reorganization energy, lambda, and driving force, DeltaG(o), derived from parabolas for the reactant and product states, was identical when starting from exergonic or endergonic parabolas. Moser and colleagues introduced a quantum mechanical correction factor to the Marcus term in order to fit experimental data. When the same correction factor was applied in the treatment for the endergonic direction by Page and colleagues, a different curve was obtained from that found with the exergonic form. We show that the difference resulted from an algebraic error in development of the endergonic equation. PMID- 17720136 TI - Affective outcomes of virtual reality exposure therapy for anxiety and specific phobias: a meta-analysis. AB - Virtual reality exposure therapy (VRET) is an increasingly common treatment for anxiety and specific phobias. Lacking is a quantitative meta-analysis that enhances understanding of the variability and clinical significance of anxiety reduction outcomes after VRET. Searches of electronic databases yielded 52 studies, and of these, 21 studies (300 subjects) met inclusion criteria. Although meta-analysis revealed large declines in anxiety symptoms following VRET, moderator analyses were limited due to inconsistent reporting in the VRET literature. This highlights the need for future research studies that report uniform and detailed information regarding presence, immersion, anxiety and/or phobia duration, and demographics. PMID- 17720137 TI - WITHDRAWN: Endosomal trafficking of EGFR regulated by hVps18 via interaction of MVB sorting machinery. AB - This article has been withdrawn at the request of the editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 17720138 TI - Fbs1 protects the malfolded glycoproteins from the attack of peptide:N-glycanase. AB - Fbs1 is a cytosolic lectin putatively operating as a chaperone as well as a substrate-recognition subunit of the SCF(Fbs1) ubiquitin ligase complex. To provide structural and functional basis of preferential binding of Fbs1 to unfolded glycoproteins, we herein characterize the interaction of Fbs1 with a heptapeptide carrying Man3GlcNAc2 by nuclear magnetic resonance (NMR) spectroscopy and other biochemical methods. Inspection of the NMR data obtained by use of the isotopically labeled glycopeptide indicated that Fbs1 interacts with sugar-peptide junctions, which are shielded in native glycoprotein, in many cases, but become accessible to Fbs1 in unfolded glycoproteins. Furthermore, Fbs1 was shown to inhibit deglycosylation of denatured ribonuclease B by a cytosolic peptide:N-glycanase (PNGase). On the basis of these data, we suggest that Fbs1 captures malfolded glycoproteins, protecting them from the attack of PNGase, during the chaperoning or ubiquitinating operation in the cytosol. PMID- 17720141 TI - Premature senescence of mesothelial cells is associated with non-telomeric DNA damage. AB - Human peritoneal mesothelial cells (HPMCs) senesce in vitro after barely few population doublings. In this report, we show that senescence of HPMCs is associated with increased accumulation of gamma-H2A.X foci, which reveal DNA double-strand breaks. Of note, already early-passage cultures contain a considerable fraction (44+/-10%) of cells bearing gamma-H2A.X foci. The gamma H2A.X foci localize predominantly to non-telomeric DNA, either in young or senescent cells. Moreover, HPMCs seem to have unusually short telomeres (approximately 3.5 kbp) despite the presence of active telomerase. These telomeres do not shorten during senescence, but the activity of telomerase decreases to undetectable levels. In addition, senescence of HPMCs is associated with mitochondrial dysfunction, as manifested by increased production of reactive oxygen species and reduced mitochondrial membrane potential. These results may indicate that premature senescence of HPMCs is largely related to oxidative stress-induced DNA damage in non-telomeric regions of the genome. PMID- 17720139 TI - Regulation of insulin secretion and GLUT4 trafficking by the calcium sensor synaptotagmin VII. AB - Insulin regulates blood glucose by promoting uptake by fat and muscle, and inhibiting production by liver. Insulin-stimulated glucose uptake is mediated by GLUT4, which translocates from an intracellular compartment to the plasma membrane. GLUT4 traffic and insulin secretion both rely on calcium-dependent, regulated exocytosis. Deletion of the voltage-gated potassium channel Kv1.3 results in constitutive expression of GLUT4 at the plasma membrane. Inhibition of channel activity stimulated GLUT4 translocation through a calcium dependent mechanism. The synaptotagmins (Syt) are calcium sensors for vesicular traffic, and Syt VII mediates lysosomal and secretory granule exocytosis. We asked if Syt VII regulates insulin secretion by pancreatic beta cells, and GLUT4 translocation in insulin-sensitive tissues mouse model. Syt VII deletion (Syt VII -/-) results in glucose intolerance and a marked decrease in glucose-stimulated insulin secretion in vivo. Pancreatic islet cells isolated from Syt VII -/- cells secreted significantly less insulin than islets of littermate controls. Syt VII deletion disrupted GLUT4 traffic as evidenced by constitutive expression of GLUT4 present at the plasma membrane of fat and skeletal muscle cells and unresponsiveness to insulin. These data document a key role for Syt VII in peripheral glucose homeostasis through its action on both insulin secretion and GLUT4 traffic. PMID- 17720140 TI - Characterization of a heat-stable protein with antimicrobial activity from Arabidopsis thaliana. AB - A heat-stable protein with antimicrobial activity was isolated from Arabidopsis thaliana plants by buffer-soluble extraction and two chromatographic procedures. The results of MALDI-TOF analysis revealed that the isolated protein shares high sequence identity with aspen SP1. To determine the exact antimicrobial properties of this protein, a cDNA encoding the protein was isolated from an A. thaliana leaf cDNA library and named AtHS1. AtHS1 mRNA was induced by exposure to external stresses, such as salicylic acid and jasmonic acid. We also analyzed the antimicrobial activity of recombinant AtHS1 expressed in Escherichia coli. This protein inhibited pathogenic fungal strains, except for Phytophthora infestans and Phytophthora nicotianae, and it exhibited antibacterial activity against E. coli and Staphylococcus aureus. These results suggest that AtHS1 shows good potential for use as a natural material in the study of antimicrobial agents. PMID- 17720142 TI - Genetic design of conditional D-glutamate auxotrophy for Bacillus subtilis: use of a vector-borne poly-gamma-glutamate synthetic system. AB - Bacillus subtilis possesses two glutamate racemase isozymes, RacE and YrpC. For the first time, we succeeded in constructing glutamate racemase-gene disruptants of B. subtilis. Phenotypic analysis of their D-glutamate auxotrophy indicated that the RacE-type glutamate racemase is important for ensuring maximum growth rate but dispensable. The YrpC-type glutamate racemase probably operates as an anaplerotic enzyme for RacE, especially under liquid culture conditions. We found novel applicability of RacE-less mutants inheriting only a marginal activity for endogenous D-glutamate supply, viz. the employment for the in vivo identification of D-glutamate-consuming systems. In fact, the genetic induction of a poly-gamma glutamate synthetic system led a RacE-less mutant to severe growth suppression, which was overcome in the presence of a high concentration of exogenous D glutamate. The results indicate that a significant amount of D-glutamate is consumed during poly-glutamate biosynthesis. To our knowledge, this is the first report of conditional D-glutamate auxotrophy for B. subtilis. PMID- 17720143 TI - Nuclear translocation of telomerase reverse transcriptase and calcium signaling in repression of telomerase activity in human lung cancer cells by fungal immunomodulatory protein from Ganoderma tsugae. AB - Recombinant fungal immunomodulatory protein, reFIP-gts, was cloned from Ganoderma tsugae and purified. In our previous study, it was shown that reFIP-gts has anti telomerase effects in A549 cells. Here, we proved that reFIP-gts entry into the cell and localization in endoplasmic reticulum can result in ER stress, thereby increasing ER stress markers (CHOP/GADD153) and intracellular calcium release in A549 cells. The use of calcium chelator restores reFIP-gts-mediated reduction in telomerase activity. These results strongly suggest that ER stress induces intracellular calcium release and results in inhibition of telomerase activity. Although reFIP-gts decreased hTERT mRNA level in both A549 and H1299 cells, only the telomerase activity in A549 cells was inhibited. Surprisingly, we found that reFIP-gts induces translocation of hTERT from the nucleus into the cytosol in A549 cells but not in H1299 cells. Using leptomycin B, nuclear export inhibitor, we showed that hTERT is not transported. Using MG132, a proteasome inhibitor, reFIP-gts also prevents hTERT translocation from proteasome degradation. Taken together, these results indicate that reFIP-gts inhibits telomerase activity in lung cancer cells through nuclear export mechanisms, which might be mediated by ER stress-induced intracellular calcium level. PMID- 17720144 TI - Effects of nonpeptide vasopressin V2 antagonist tolvaptan in rats with heart failure. AB - Similar to other neurohormones that are activated in chronic heart failure (CHF), circulating arginine vasopressin (AVP) is elevated in patients with CHF. The precise role of AVP in the pathophysiology of cardiovascular disease is controversial. AVP is a peptide hormone that contributes to water retention and vasoconstriction in CHF through effects on V(2) and V(1a) receptors, respectively. In the present study, the effect of V(2) receptor (V(2)R) blockade using tolvaptan was assessed in a rat model of myosin-induced experimental autoimmune myocarditis. CHF was elicited in Lewis rats by immunization with porcine cardiac myosin, and 28 days after immunization rats were treated for 28 days with oral tolvaptan (3 or 10mg/(kg day)) or vehicle. CHF was characterized by left ventricular remodeling and impaired systolic and diastolic function. Chronic V(2)R blockade increased urine volume and urinary AVP excretion and decreased urine osmolality but had no natriuretic effect, and as a result caused increases in plasma osmolality and sodium. High doses of tolvaptan markedly elevated electrolyte-free water clearance. V(2)R blockade did not activate the renin-angiotensin system, not influence cardiac remodeling, cardiac function, or survival. The upregulation of aquaporin 2 protein in the kidney of CHF rats was inhibited by the administration of V(2)R antagonist. These results suggest that in a rat model of CHF, AVP plays a major role in water retention through the renal V(2)R. PMID- 17720145 TI - The intestinal anti-inflammatory effects of the novel agent UR-1505 in the TNBS model of rat colitis are mediated by T-lymphocyte inhibition. AB - UR-1505 is a novel pentafluoropropoxy derivative of salicylic acid, selected from a series of salicylate derivatives, according to their activity as inhibitors of T-lymphocyte activation. This study describes the anti-inflammatory activity of UR-1505 on trinitrobenzenesulphonic acid-induced colitis in rat, an experimental model that resembles to Crohn's disease (CD), as well as its in vitro effects on T-cells and bone marrow-derived macrophages (BMDM) activation. UR-1505 showed intestinal anti-inflammatory effect, associated with reduced colonic levels of TNFalpha and LTB(4), inhibition of the expression of IFNgamma and iNOS, and lower colonic leukocyte infiltration. The in vitro assays revealed that UR-1505 also inhibited T-lymphocyte proliferation and IL-12/IFNgamma production, two of the main pro-inflammatory cytokines involved in the pathogenesis of CD. However, UR 1505 did not modify LPS- nor IFNgamma-induced activation in BMDM. Thus, UR-1505 specifically affects T-cells without modifying the activation of BMDM. In conclusion, the intestinal anti-inflammatory activity of UR-1505 seems to be mediated by a reduction in the recruitment of immune cells to the inflammatory foci, together with the inhibition of T-cell activation. These results suggest that UR-1505 may be an interesting candidate to be explored for the treatment of CD. PMID- 17720147 TI - Diffusion tensor imaging of the superior longitudinal fasciculus and working memory in recent-onset schizophrenia. AB - BACKGROUND: Structural and functional abnormalities in frontal-parietal circuitry are thought to be associated with working memory (WM) deficits in patients with schizophrenia. This study examines whether recent-onset schizophrenia is associated with anatomical changes in the superior longitudinal fasciculus (SLF), the main frontal-parietal white matter connection, and whether the integrity of the SLF is related to WM performance. METHODS: We applied a novel registration approach (Tract-Based Spatial Statistics [TBSS]) to diffusion tensor imaging data to examine fractional anisotropy (FA) in the left and right SLF in 12 young adult patients with recent-onset schizophrenia and 17 matched control subjects. RESULTS: Schizophrenia patients showed lower FA values than control subjects across the entire SLF, with particular deficits on the left SLF. Fractional anisotropy values were correlated with performance on a verbal WM task in both patient and control groups in the left but not right SLF. CONCLUSIONS: Recent onset schizophrenia patients show deficits in frontal-parietal connections, key components of WM circuitry. Moreover, the integrity of this physiological connection predicted performance on a verbal WM task, indicating that this structural change may have important functional implications. These findings support the view that schizophrenia is a disorder of brain connectivity and implicate white matter changes detectable in the early phases of the illness as one source of this dysfunction. PMID- 17720149 TI - Atrial cardiomyocyte tachycardia alters cardiac fibroblast function: a novel consideration in atrial remodeling. AB - OBJECTIVE: Atrial fibrillation (AF) causes tachycardia-induced atrial electrical remodeling, contributing to the progressive nature of the arrhythmia. Ventricular dysfunction due to a rapid response to AF can cause structural remodeling, but whether AF itself directly promotes atrial fibrosis is controversial. This study investigated the hypothesis that rapid atrial cardiomyocyte activation produces factors that influence atrial fibroblast proliferation and secretory functions. METHODS: Cultured canine atrial fibroblasts were treated with medium from rapidly paced atrial cardiomyocytes, non-paced cardiomyocytes and cardiomyocyte-pacing medium only, and analyzed by [(3)H]thymidine incorporation, Western blot and real time RT-PCR. RESULTS: Rapidly-paced cardiomyocyte-conditioned medium reduced [(3)H]thymidine uptake compared to non-paced cardiomyocyte-conditioned medium and medium alone (approximately 85%, P<0.01). Rapidly-paced cardiomyocyte medium increased alpha SMA protein (approximately 55%, p<0.001), collagen-1 (approximately 85%, P<0.05) and fibronectin-1 (approximately 205%, P<0.05) mRNA expression vs. controls. The angiotensin-1 receptor blocker valsartan attenuated pacing-induced alpha SMA changes but did not affect fibroblast proliferation. Suppression of contraction with blebbistatin did not prevent tachypacing-induced changes in [(3)H]thymidine uptake or alpha SMA upregulation, pointing to a primary role of electrical over mechanical cardiomyocyte activity. Atrial tissue from 1-week atrial-tachypaced dogs with ventricular rate control similarly showed upregulation of alpha SMA protein (approximately 40%, P<0.05), collagen-1 (approximately 380%, P<0.01) and fibronectin-1 (approximately 430%, P<0.001) mRNA versus shams. CONCLUSIONS: Rapidly-paced cardiomyocytes release substances that profoundly alter cardiac fibroblast function, inducing an activated myofibroblast phenotype that is reflected by increased ECM-gene expression in vivo. These findings are consistent with recent observations that AF per se may cause ECM remodeling, and have potentially important consequences for understanding and preventing the mechanisms underlying AF progression. PMID- 17720150 TI - Induction of tumor antigen-specific cytotoxic T cell responses in naive mice by latex microspheres-based artificial antigen-presenting cell constructs. AB - Latex microspheres-based artificial antigen-presenting cell constructs (aAPCs) are proved to be valuable tools to expand T cells ex vivo for adoptive cell therapy, but little is known about their potential for active immunization. In this report, HLA-A2/peptide tetramers were generated and co-coated with anti mouse CD28 monoclonal antibody onto surface of cell-sized latex microspheres followed by immunization of naive HLA-A2/K(b) transgenic mice. Five- to six-fold expansion of tumor antigen-specific CTLs was observed in the spleen after three rounds of immunization. The consequent splenocytes can efficiently recognize endogenously expressed tumor antigen on the surface of human target cells and cytolyze the tumor cells in an antigen-specific manner. This report provides initially the experimental evidence that latex microspheres-based aAPCs can effectively prime antigen-specific CTL proliferation and cytolysis in naive mice. This may contribute to a better insight into the potential of microspheres-based aAPCs for active immunization. PMID- 17720151 TI - Functional analysis of cis-regulatory regions within the dioxin-inducible CYP1A promoter/enhancer region from zebrafish (Danio rerio). AB - In vitro mutagenesis was utilized to render the various xenobiotic response elements (XREs) within the zebrafish CYP1A promoter/enhancer region non functional either independently or in combination. Reporter gene assays revealed that only XRE4, XRE7, and XRE8 contributed to maximal TCDD-mediated induction of luciferase and that the contribution of each XRE to maximal induction was not equal. XRE4 and XRE7 were capable of functioning independently, while XRE8 alone could not support TCDD-mediated induction but was required for the ability of XRE4 and XRE7 to support maximal induction. These results were observed in cell lines derived from human, mouse and zebrafish. Mutagenesis of 3' nucleotides flanking the non-functional XRE5, and functional XRE4 did not alter the function of these XREs in cell culture. In silico analyses revealed the presence of putative Sp1, AP2, CREB, and two HNF-3 transcription factor binding sites that were localized to common positions within the enhancer region of both the mouse and zebrafish CYP1A genes. In vitro mutagenesis of the binding sites showed that loss of the Sp1 or AP2 sites had minimal impact on TCDD-mediated gene induction while loss of the putative CREB site resulted in a modest decrease in basal and inducible activity and mutation of the HNF-3 reduced inducible activity by >90% of controls. Collectively, these findings suggest that the presence of XREs is not the sole determinant for regulation of aryl hydrocarbon receptor (AHR) mediated gene and do not function in an additive manner. PMID- 17720148 TI - Hypometabolism and altered cerebrospinal fluid markers in normal apolipoprotein E E4 carriers with subjective memory complaints. AB - BACKGROUND: We examined whether cerebral metabolic rates for glucose (CMRglc) on 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) and cerebrospinal fluid (CSF) markers of Alzheimer's disease (AD) are altered in cognitively normal apolipoprotein E (ApoE) E4 carriers with subjective memory complaints (SMC). METHODS: Twenty-eight middle-aged normal subjects (NL) were examined, including 13 E4 carriers (E4+; 6 with SMC [SMC+] and 7 without SMC [SMC ]) and 15 noncarriers (E4-; 7 SMC+ and 8 SMC-). Subjects received an FDG-PET scan and a lumbar puncture to measure CSF total (T-Tau) and hyperphosphorylated tau(231) (P-Tau), 40 and 42 amino acid forms of beta-amyloid (Abeta40 and Abeta42), and F(2)-isoprostane (IP). RESULTS: As compared with E4-, E4+ subjects showed decreased CMRglc in AD-related brain regions and associated higher CSF IP, P-Tau, T-Tau, and P-Tau/Abeta42 levels (p's < .05). As compared with SMC-, SMC+ subjects showed reduced parietotemporal and parahippocampal gyrus (PHG) CMRglc. A significant ApoE by SMC status interaction was found, with the E4+/SMC+ showing the lowest PHG CMRglc and the highest CSF IP, P-Tau, and P-Tau/Abeta42 levels as compared with all other subgroups (p's < or = .05). The combination of CSF and CMRglc measures significantly improved the accuracy of either measures alone in discriminating ApoE groups (86% accuracy, odds ratio [OR] = 4.1, p < .001) and E4+/SMC+ from all other subgroups (86% accuracy, OR = 3.7, p = .005). Parahippocampal gyrus CMRglc was the most accurate discriminator of SMC groups (75% accuracy, OR = 2.4, p < .001). CONCLUSIONS: Normal E4 carriers with SMC show altered AD-related CSF and FDG-PET measures. Longitudinal studies are needed to assess whether these brain abnormalities foreshadow clinical decline. PMID- 17720152 TI - The function of Dmrt genes in vertebrate development: it is not just about sex. AB - The Dmrt genes encode a large family of transcription factors whose function in sexual development has been well studied in invertebrates and vertebrates. Their expression pattern is not restricted to the developing gonads, indicating that Dmrt genes might regulate other developmental processes. Here we review the expression pattern of several members of this family across species and summarize recent findings on the function of a subset of these genes in non-gonadal tissues. PMID- 17720153 TI - Melatonin treatment improves the antioxidant status and decreases lipid content in brain and liver of rats. AB - This study examines the effect of a daily administration of melatonin for 45 days at two doses (0.5 and 1.0 mg/kg body wt.) on antioxidant status, lipid peroxidation and lipid profile in the brain and liver in rats. Both doses of melatonin caused a significant decrease in lipid peroxidation and the levels of cholesterol, phospholipids, triglycerides and free fatty acids in the examined tissues. Concomitantly, the treatment with melatonin augmented the activity of the brain and liver antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase as well as increased glutathione levels. These results offer a support to the hypothesis that melatonin in pharmacological amounts effectively reduces oxidative stress and acts as an antihyperlipidemic agent. PMID- 17720155 TI - Expression profiles of mRNA transcript variants encoding the human inhibitor of growth tumor suppressor gene family in normal and neoplastic tissues. AB - The INhibitor of Growth (ING) tumor suppressor gene family is important in regulating cell fate and reads the epigenetic code by interacting specifically with methylated histone H3. Several transcript variants are expressed from the five ING genes but nomenclature for these variants are not consistent in the literature, and very little is known regarding transcript variant expression in normal human tissues and during development. Here we propose a standardized nomenclature for human ING gene family transcript variants and present an expression analysis using real-time quantitative PCR. We establish the steady state levels of eleven human ING mRNA transcript variants across several fetal, adult, and tumor tissues as well as in cancer-derived cell lines. Consistent with their roles as type II tumor suppressors, we find up to 10,000-fold reduction in many transcript variants in a subset of neoplastic cells. We also find considerable variation in expression levels in different tissues, with up to 1 million-fold higher expression of some ING transcripts in adult, compared to fetal counterparts, particularly in the brain cerebral cortex. These results show differential expression of specific subsets of ING1-5 transcript variants in tissues that may influence the degree to which these variants contribute to epigenetic regulation in cancer and development. PMID- 17720156 TI - 14-3-3-dependent inhibition of the deubiquitinating activity of UBPY and its cancellation in the M phase. AB - The deubiquitinating enzyme UBPY, also known as USP8, regulates cargo sorting and membrane traffic at early endosomes. Here we demonstrate the regulatory mechanism of the UBPY catalytic activity. We identified 14-3-3 epsilon, gamma, and zeta as UBPY-binding proteins using co-immunoprecipitation followed by mass spectrometric analysis. The 14-3-3 binding of UBPY was inhibited by mutating the consensus 14-3 3-binding motif RSYS(680)SP, by phosphatase treatment, and by competition with the Ser(680)-phosphorylated RSYS(680)SP peptide. Metabolic labeling with [(32)P]orthophosphate and immunoblotting using antibody against the phosphorylated 14-3-3-binding motif showed that Ser(680) is a major phosphorylation site in UBPY. These results indicated that 14-3-3s bind to the region surrounding Ser(680) in a phosphorylation-dependent manner. The mutation at Ser(680) led to enhanced ubiquitin isopeptidase activity of UBPY toward poly ubiquitin chains and a cellular substrate, epidermal growth factor receptor, in vitro and in vivo. Moreover, addition of 14-3-3epsilon inhibited the UBPY activity in vitro. Finally, UBPY was dephosphorylated at Ser(680) and dissociated from 14-3-3s in the M phase, resulting in enhanced activity of UBPY during cell division. We conclude that UBPY is catalytically inhibited in a phosphorylation dependent manner by 14-3-3s during the interphase, and this regulation is cancelled in the M phase. PMID- 17720154 TI - Level of endothelial cell apoptosis required for a significant decrease in microvessel density. AB - Endothelial cell apoptosis plays a critical role in the disruption of blood vessels mediated by natural inhibitors of angiogenesis and by anti-vascular drugs. However, the proportion of endothelial cells required to mediate a significant decrease in microvessel density is unknown. A system based on an inducible caspase (iCaspase-9) offers a unique opportunity to address this question. The dimerizer drug AP20187 induces apoptosis of human dermal microvascular endothelial cells stably transduced with iCaspase-9 (HDMEC-iCaspase 9), but not control cells (HDMEC-LXSN). Here, we generated blood vessels containing several HDMEC-iCaspase-9:HDMEC-LXSN ratios, and developed a mathematical modeling involving a system of differential equations to evaluate experimentally inaccessible ratios. A significant decrease in capillary sprouts was observed when at least 17% of the endothelial cells underwent apoptosis in vitro. Exposure to vascular endothelial growth factor (VEGF(165)) did not prevent apoptosis of HDMEC-iCaspase-9, but increased the apoptotic requirement for sprout disruption. In vivo experiments showed the requirement of at least 22% apoptotic endothelial cells for a significant decrease in microvascular density. The combined use of biological experimentation with mathematical modeling allowed us to conclude that apoptosis of a relatively small proportion of endothelial cells is sufficient to mediate a significant decrease in microvessel density. PMID- 17720157 TI - Transforming growth factor beta-producing Foxp3(+)CD8(+)CD25(+) T cells induced by iris pigment epithelial cells display regulatory phenotype and acquire regulatory functions. AB - The ocular pigment epithelial (PE) cells convert T cells into T regulators (Tregs) in vitro. The PE-induced Tregs fully suppress activation of bystander responder T cells. Iris PE (IPE) cells from anterior segment in the eye produce costimulatory molecules and transforming growth factor beta (TGFbeta) that is delivered to CD8(+) Tregs. We have now examined whether T cells exposed to cultured IPE express CD25 and Foxp3, and to determine if the CD25(+) IPE-exposed T cells display regulatory functions in vitro. We have found that cultured B7 2(+) IPE converted CTLA-4(+) T cells into CD25(+) Tregs that suppress the activation of bystander T cells. The CD8(+) IPE-induced Tregs constitutively expressed CD25. Through TGFbeta-TGFbeta receptor interactions, the IPE converted these T cells into CD25(+) Tregs that express Foxp3 transcripts. The CD8(+) IPE induced Tregs produced immunoregulatory cytokines, e.g., interleukin-10 and TGFbeta. In addition, IPE-exposed T cells that downregulated Foxp3 mRNA failed to acquire the regulatory function. In conclusion, ocular pigment epithelial cells convert CD8(+) T cells into CD25(+) Tregs by inducing the transcription factor Foxp3. Thus, T cells that encounter ocular parenchymal cells participate in the T cell suppression. PMID- 17720158 TI - On the relationship between lens stiffness and accommodative amplitude. AB - The purpose of this study was to investigate the relationship between the stiffness of the material comprising the lens and the loss of accommodative amplitude with age. We used a validated mechanical model to determine the changes in the shape of the lens during accommodation and disaccommodation. The relative contribution of lens stiffness to loss of accommodative amplitude with age was determined by varying lens stiffness in the model. The changes in lens stiffness with age were based on the results of two recently published studies. In the first study we showed that lens stiffness increases exponentially with age, and in the second study we showed that there is a considerable stiffness gradient within the lens that changes with age. The results of both studies were incorporated in the mechanical model. The model showed that it is not the increasing stiffness of the lens with age, but rather the changing stiffness gradient that influences accommodative amplitude. The results show that the changing stiffness gradient in the lens may be responsible for almost the entire loss of accommodation with age. PMID- 17720162 TI - Comparative water metabolism of Barrow Island macropodid marsupials: hormonal versus behavioural-dependent mechanisms of body water conservation. AB - Seasonal variations in rates of water turnover were measured over a 7-year period in four species of macropodid marsupials (Lagorchestes conspicillatus, Bettongia lesueur, Petrogale lateralis and Macropus robustus isabellinus), on Barrow Island off the arid Pilbara coast of Western Australia. These ranged from over 100 mL kg(-0.82) d(-1) in wet seasons to as low as 28.2 mL kg(-0.82) d(-1) in dry seasons in the Spectacled hare wallaby, L. conspicillatus. Plasma osmolality increased significantly in both Barrow Island euros (M. robustus isabellinus) and Spectacled hare wallabies in November 1994, in the driest year yet recorded on the island. In contrast, there was no change in plasma osmolality of the other two species (Black-footed rock wallaby, P. lateralis and Lesueur's burrowing bettong, B. lesueur) that exploit cool and humid thermal refugia such as caves and underground warrens to avoid diurnal temperature extremes. Plasma levels of the marsupial antidiuretic hormone (ADH), lysine vasopressin (LVP), were for the most part below the detectable limit of the assay of 0.41 pg mL(-1) in rock wallabies and bettongs, but reached high levels of 16.7+/-4.6 pg mL(-1) and 20.25+/-5.1 pg mL(-1) in euros and hare wallabies, respectively, in dry seasons. LVP levels were positively correlated with plasma osmolality in both euros and hare wallabies, and negatively correlated with total body water content in euros, supporting its role as an antidiuretic hormone in these two species. The study highlights the importance of environmental features, such as caves and underground warrens, which are critical for the long-term survival of endangered species such as the Black-footed rock wallaby and the Lesueur's bettong. These species appear to lack ADH-controlled renal systems for the conservation of body water and are thus dependent on behavioural strategies for the maintenance of fluid homeostasis in arid environments. PMID- 17720161 TI - Neospora caninum: functional inhibition of protein disulfide isomerase by the broad-spectrum anti-parasitic drug nitazoxanide and other thiazolides. AB - Nitazoxanide (NTZ) and several NTZ-derivatives (thiazolides) have been shown to exhibit considerable anti-Neospora caninum tachyzoite activity in vitro. We coupled tizoxanide (TIZ), the deacetylated metabolite, to epoxy-agarose-resin and performed affinity chromatography with N. caninum tachyzoite extracts. Two main protein bands of 52 and 43kDa were isolated. The 52kDa protein was readily recognized by antibodies directed against NcPDI, and mass spectrometry confirmed its identity. Poly-histidine-tagged NcPDI-cDNA was expressed in Escherichia coli and recombinant NcPDI (recNcPDI) was purified by Co2+-affinity chromatography. By applying an enzyme assay based on the measurement of insulin crosslinking activity, recNcPDI exhibited properties reminiscent for PDIs, and its activity was impaired upon the addition of classical PDI inhibitors such as bacitracin (1 2mM), para-chloromercuribenzoic acid (0.1-1mM) and tocinoic acid (0.1-1mM). RecNcPDI-mediated insulin crosslinking was inhibited by NTZ (5-100 microM) in a dose-dependent manner. In addition, the enzymatic activity of recNcPDI was inhibited by those thiazolides that also affected parasite proliferation. Thus, thiazolides readily interfere with NcPDI, and possibly also with PDIs from other microorganisms susceptible to thiazolides. PMID- 17720163 TI - Relevance of ovarian signaling for the early behavioral transition from estrus to pregnancy in the female rabbit. AB - During estrus, the female domestic rabbit (Oryctolagus cuniculus) displays scent marking behavior (chinning), which is immediately inhibited after mating, temporarily recovers, and then declines and remains inhibited across pregnancy. Chinning is inhibited by progesterone (P) and the activation of the progesterone receptor (PR), but it is unlikely that P participates in the "acute" (immediate) or "early" inhibition of chinning (24 to 96 h post-mating, before plasma P levels rise). Since PR is activated in a ligand-independent manner by a variety of signaling molecules, some of which (e.g., GnRH) are also associated with reflexive ovulation in this species, we hypothesized that neurochemical/neuroendocrine signals associated with mating activate PR, resulting in the inhibition of chinning. In Experiment 1, we tested whether the PR antagonist, RU486 (20 mg, injected s.c. at -1 h, or at -7 h and +3 h relative to mating) prevented the post-mating inhibition of chinning in intact females. RU486 did not prevent the post-mating decline in chinning, indicating that PR activation associated with mating is not necessary for this effect. In Experiment 2, we used ovariectomized (OVX), estradiol benzoate (EB)-treated females to test the hypothesis that ovarian signaling is necessary for the post-mating inhibition of chinning. The acute inhibition of chinning occurred in OVX females, but the early inhibition was absent. We conclude that ovarian signaling is necessary for the early, but not acute, post-mating inhibition of chinning. The PR seems not to participate in either of these phases. PMID- 17720164 TI - Is 38 weeks late enough for elective cesarean delivery? PMID- 17720160 TI - The role of cyclic AMP signaling in promoting axonal regeneration after spinal cord injury. AB - The failure of axons to regenerate after spinal cord injury remains one of the greatest challenges facing both medicine and neuroscience, but in the last 20 years there have been tremendous advances in the field of spinal cord injury repair. One of the most important of these has been the identification of inhibitory proteins in CNS myelin, and this has led to the development of strategies that will enable axons to overcome myelin inhibition. Elevation of intracellular cyclic AMP (cAMP) has been one of the most successful of these strategies, and in this review we examine how cAMP signaling promotes axonal regeneration in the CNS. Intracellular cAMP levels can be increased through a peripheral conditioning lesion, administration of cAMP analogues, priming with neurotrophins or treatment with the phosphodiesterase inhibitor rolipram, and each of these methods has been shown to overcome myelin inhibition both in vitro and in vivo. It is now known that the effects of cAMP are transcription dependent, and that cAMP-mediated activation of CREB leads to upregulated expression of genes such as arginase I and interleukin-6. The products of these genes have been shown to directly promote axonal regeneration, which raises the possibility that other cAMP-regulated genes could yield additional agents that would be beneficial in the treatment of spinal cord injury. Further study of these genes, in combination with human clinical trials of existing agents such as rolipram, would allow the therapeutic potential of cAMP to be fully realized. PMID- 17720165 TI - Ethnopharmacology and malaria: new hypothetical leads or old efficient antimalarials? AB - New treatments are urgently needed to curb and eradicate malaria in developing countries. As most people living in malarial endemic areas use traditional medicine to fight this disease, why have new treatments not emerged recently from ethnopharmacology-oriented research? The rationale and limitations of the ethnopharmacological approach are discussed in this paper, focusing on ethnopharmacology methodologies and techniques used for assessing botanical samples for their antimalarial properties. Discrepancies often observed between strong ethnopharmacological reputation and laboratory results are discussed, as well as new research perspectives. PMID- 17720166 TI - Microparticles derived from endothelial progenitor cells in patients at different cardiovascular risk. AB - OBJECTIVES: Exposure to cardiovascular risk factors causes the release of pro atherogenic microparticles from vascular cells and reduces the number of the atheroprotective endothelial progenitor cells (EPCs). We investigated whether microparticles shedding from EPCs are detectable in cultures of EPCs and in the circulation of subjects with various degrees of cardiovascular risk. We also investigated the relationship of EPCs-derived microparticles to cardiovascular risk factors and aortic stiffness, a marker of cardiovascular risk and impaired vascular repair by EPCs. METHODS AND RESULTS: We estimated the 10-year Framingham risk score in 105 individuals with various degrees of cardiovascular risk and measured the number of circulating EPCs, EPCs-derived microparticles (CD34+/KDR+) and aortic stiffness. Release of CD34+/KDR+ microparticles was tested in cultures of EPCs exposed to hydrogen-peroxide. CD34+/KDR+ microparticles were found in EPCs cultures incubated with hydrogen-peroxide. Framingham risk was associated with EPCs (r=-0.47, p<0.001) and CD34+/KDR+ microparticles (r=0.56, p<0.001). Low EPCs (r=-0.59, p<0.001) and high CD34+/KDR+ microparticle (r=0.57, p<0.001) levels were predictors of aortic stiffness, independent of the Framingham risk. CONCLUSIONS: EPCs undergo fragmentation into microparticles when exposed to a pro apoptotic milieu. Increased microparticle shedding from EPCs may reduce circulating EPCs levels and may thus contribute to increase aortic stiffness beside traditional risk factors. PMID- 17720167 TI - Multidetector computed tomography coronary artery plaque predictors of stress induced myocardial ischemia by SPECT. AB - BACKGROUND: Atherosclerosis imaging by multidetector computed tomography (MDCT) detects coronary artery plaque extent, distribution, location and composition. In contrast, functional imaging by single-photon emission computed tomography (SPECT) identifies perfusion defects known to predict prognosis of coronary heart disease (CHD). We sought to determine whether anatomic measures of plaque by MDCT predict functional measures of CHD by SPECT and thus, serve as measures of adverse cardiovascular prognosis. METHODS AND RESULTS: Consecutive low-to intermediate risk symptomatic patients without known CHD (n=163) underwent both stress SPECT and MDCT. MDCT plaque extent and distribution were graded by a segment stenosis score (summation of luminal obstruction in all coronary segments) and segment involvement score (summation of segments exhibiting any plaque), respectively. Plaque location was assessed with a segments-at-risk score (plaque extent weighted by proximity) and a modified Duke CAD index. Plaque composition was graded as non-calcified, calcified and mixed. SPECT findings- summed stress (SSS), rest (SRS) and difference (SDS) scores--were compared to MDCT plaque scores. In univariate analyses, segment stenosis score (p=0.006), segments-at-risk score (p=0.002), Duke CAD index (p=0.02), and mixed plaque score (p=0.01) predicted severely abnormal SPECT. Highest compared to lowest quartile mixed plaque scores were predictive of higher SSS (8.1+/-10.3 versus 3.5+/-5.7, p<0.001), SRS (3.2+/-7.7 versus 0.9+/-3.1, p=0.008), and SDS (4.9+/-6.4 versus 2.6+/-3.9, p=0.012). In contrast, higher segment involvement scores, calcified and non-calcified plaque scores did not predict higher SPECT measures of ischemia. In multivariable analyses, comparing highest to lowest quartiles, individuals with high segment stenosis scores [odds ratio (OR) 1.97 (1.22-3.39), p=0.008], segments-at-risk scores [OR 1.71 (1.24-2.58), p=0.005], highest risk Duke CAD index category [OR 2.25 (1.12-4.41), p=0.02], and mixed plaque scores [OR 1.64 (1.10-2.43), p=0.01] had more severely abnormal SPECT scans. CONCLUSIONS: In low-to-intermediate risk patients without known CHD, MDCT coronary artery plaque assessment successfully identify patients at higher risk of increased extent, severity and reversibility of myocardial perfusion defects by SPECT. Anatomic MDCT findings, including plaque extent, location and composition, are independent predictors of functional ischemia and severe CHD by SPECT and thus, represent markers of adverse cardiovascular prognosis prior to the occurrence of clinical cardiovascular events. PMID- 17720159 TI - Neuroinflammatory mechanisms in Parkinson's disease: potential environmental triggers, pathways, and targets for early therapeutic intervention. AB - Most acute and chronic neurodegenerative conditions are accompanied by neuroinflammation; yet the exact nature of the inflammatory processes and whether they modify disease progression is not well understood. In this review, we discuss the key epidemiological, clinical, and experimental evidence implicating inflammatory processes in the progressive degeneration of the dopaminergic (DA) nigrostriatal pathway and their potential contribution to the pathophysiology of Parkinson's disease (PD). Given that interplay between genetics and environment are likely to contribute to risk for development of idiopathic PD, recent data showing interactions between products of genes linked to heritable PD that function to protect DA neurons against oxidative or proteolytic stress and inflammation pathways will be discussed. Cellular mechanisms activated or enhanced by inflammatory processes that may contribute to mitochondrial dysfunction, oxidative stress, or apoptosis of dopaminergic (DA) neurons will be reviewed, with special emphasis on tumor necrosis factor (TNF) and interleukin-1 beta (IL-1beta) signaling pathways. Epigenetic factors which have the potential to trigger neuroinflammation, including environmental exposures and age associated chronic inflammatory conditions, will be discussed as possible 'second hit' triggers that may affect disease onset or progression of idiopathic PD. If inflammatory processes have an active role in nigrostriatal pathway degeneration, then evidence should exist to indicate that such processes begin in the early stages of disease and that they contribute to neuronal dysfunction and/or hasten neurodegeneration of the nigrostriatal pathway. Therapeutically, if anti inflammatory interventions can be shown to rescue nigral DA neurons from degeneration and lower PD risk, then timely use of anti-inflammatory therapies should be investigated further in well-designed clinical trials for their ability to prevent or delay the progressive loss of nigral DA neurons in genetically susceptible populations. PMID- 17720168 TI - Sequential based analysis of Intima-Media Thickness (IMT) in common carotid artery studies. AB - INTRODUCTION: Carotid Intima-Media Thickness (IMT) is used widely to assess an individual's risk of myocardial infarction and stroke. Although significant associations have been showed, IMT as used in major studies does not improve prediction of cardiovascular events much compared to traditional risk factors. Therefore, a new approach to IMT-measurements is sought-after by examining the wall structure continuously throughout several heart cycles. MATERIALS AND METHODS: Computerized single-image analysis (IA) and sequential analysis (SA) were used to assess latter's capability in predicting risk of cardiovascular disease and to compare both. Healthy subjects (mean+/-S.D., age 46.1+/-5.6 years, n=490) were compared with subjects suffering from confirmed coronary artery disease (CAD) (mean+/-S.D., age 47.3+/-6.2 years, n=51). RESULTS: SA could differentiate between both groups better then single IA, especially when looking at the maximal and mean IMT-values (SA<-->IA, p<0.01<-->p<0.05). The area under the curve (AUC) for maximal and mean IMT was greater for sequences then for single images as well. DISCUSSION: Due to our findings sequential analysis can offer an extensive and complete examination of the carotid wall with a maximal reduction of bias. Commonly used IA may disguise vascular conditions and therefore the patient's risk, since IMT-values, as proven with SA, seems to usually be higher. Therefore, the need for further studies arises, examining if and to what extend common IMT-studies underestimate differences between groups. PMID- 17720169 TI - Regression simulation of the dependence of forced expiratory tracheal noises duration on human respiratory system biomechanical parameters. AB - BACKGROUND: Estimating the duration of forced exhalation tracheal noises shows promise for recognizing bronchial obstruction. OBJECTIVE: Experimental simulation of an influence of biomechanical parameters on the duration of normal forced exhalation tracheal noises. METHOD AND MATERIALS: Thirty-two healthy non-smoking men aged 16-22 years were examined. The duration of noises, the parameters of computer spirometry, and the maximum static expiratory pressure are recorded. These data were analyzed by means of multiple linear regression simulation for logarithms of the elements of the proportionality relation obtained with the use of a one-component biomechanical model of forced exhalation and a linearized approximation of flow-volume curve. RESULTS: Dependence between duration of the forced expiratory noises recorded on human trachea and the product of forced volume capacity (in power of 1.05 +/- 0.27), maximum static expiratory pressure (in power of 0.46 +/- 0.23), equivalent expiratory resistance in the stage of functional expiratory stenosis (in power of 0.72 +/- 0.15 in healthy is an estimate of the equivalent expiratory resistance of human bronchial tree in the functional expiratory stenosis phase, whereas in patients with bronchial obstruction it is supposed to take into account an excess of noise generation time compared with the time predicted from normal individual value of this resistance. PMID- 17720170 TI - Optimisation of multilinear gradient elutions in reversed-phase liquid chromatography using ternary solvent mixtures. AB - The multilinear gradient elution theory for binary mobile phases in reversed phase liquid chromatography presented in [P. Nikitas, A. Pappa-Louisi, A. Papageorgiou, J. Chromatogr. A 1157 (2007) 178] is extended to ternary gradients. For the evaluation of this theory and the performance of the various fitting and optimisation algorithms we used 13 o-phthalaldehyde (OPA) derivatives of amino acids with mobile phases modified by acetonitrile and methanol. It is shown that the theory can lead to high quality predictions of the retention times under gradients elutions and optimisation of ternary gradients provided that we use a six-parameter expression for the logarithm of the retention factor, lnk, and the adjustable parameters of this expression are determined from ternary isocratic data. PMID- 17720171 TI - Development of a dispersive liquid-liquid microextraction method for organophosphorus flame retardants and plastizicers determination in water samples. AB - A fast, inexpensive and efficient sample preparation method for the determination of 10 organophosphorus compounds in water samples is presented. Analytes were extracted using the dispersive liquid-liquid microextraction (DLLME) technique and determined by gas chromatography with nitrogen-phosphorus detection (GC-NPD). The influence of several variables (e.g. type and volume of dispersant and extraction solvents, ionic strength, shaking time and mode, etc.) on the performance of the sample preparation step was carefully evaluated. Under final working conditions, 1 mL of acetone containing a 2% of 1,1,1-trichloroethane (20 microL) was added to 10 mL of water with 20% of sodium chloride. The ternary mixture was centrifuged at 3500 rpm to allow phase separation. After removing the aqueous supernatant, an aliquot of the settled extract was injected in the GC-NPD system. Under the above conditions, the method provided enrichment factors between 190 and 830 times (depending on the considered compound), relative standard deviations below 10%, except for tris(2-ethylhexyl) phosphate (TEHP), and quantification limits between 0.01 and 0.08 ng/mL. Matrix effects were assessed using different water samples, and accuracy was evaluated by comparison with solid-phase microextraction. PMID- 17720172 TI - A solution for isomerization of pyrethroid insecticides in gas chromatography. AB - Isomerization of pyrethroid insecticides was observed during extraction and gas chromatography (GC) analysis. An improvement in sensitivity was noted for pyrethroids in sediment extracts in comparison to pure solvent. Stability of pyrethroids using different solvents and analyte additives were investigated, and GC injection conditions were optimized. Polar solvents enhanced pyrethroid isomerization, while hexane was the best choice as an analytical solvent. Acetic acid was used successfully as an isomer-stabilizing agent for GC analysis of pyrethroids. Acidified (0.1% acetic acid) hexane prevented pyrethroid isomerization, increased peak intensity up to 1.9 times, and calibration curve linearity (relative standard deviation for response factors) 0.8-12.5 times compared to hexane alone. PMID- 17720174 TI - Consequences of the radial heterogeneity of the column temperature at high mobile phase velocity. AB - When a high velocity stream of mobile phase percolates through a chromatographic column, the bed cannot remain isothermal. Due to the mobile phase decompression, heat is generated along the column. Longitudinal and radial temperature gradients take place along and across its bed. The various consequences of this thermal heterogeneity are calculated and their effects on the column efficiency investigated for a 0.46 cm x 25 cm stainless steel column packed with 5 microm particles. The maximum pressure drop applied was varied from 0.1 to 2 kbar. The amplitude of the longitudinal temperature gradient can be estimated on the basis of the integral heat balance equation applied to the whole column and of measurements of the eluent temperature at the column exit. Assuming that the radial gradient is parabolic and the longitudinal gradient linear, the amplitude of the radial gradient can be determined on the basis of the energy balance across the column and of direct measurements of the radial gradient at high inlet pressures. A radial temperature gradient causes a radial distribution of the eluent viscosity, hence of its local velocity. The result is that bands move faster in their center than along the wall, become warped, hence a radial concentration gradient, similar in origin to the one observed in open cylindrical tubes. Diffusion relaxes this gradient. If there is only a longitudinal temperature gradient, the column efficiency would be 30% smaller for a 2 kbar pressure drop than if there is no longitudinal temperature gradient. However, when both a longitudinal and a radial temperature gradient coexist, there is a large loss of efficiency. If the influence of the diffusive relaxation of the radial concentration gradient is neglected, the peak shape would be broad and exhibit a marked shoulder. PMID- 17720175 TI - Sensitive determination of free benzophenone-3 in human urine samples based on an ionic liquid as extractant phase in single-drop microextraction prior to liquid chromatography analysis. AB - Benzophenone-3 (BZ3), one of the compounds most commonly used as UV filter in cosmetic products, can be absorbed through the skin into the human body, since it can be found at trace levels in urine from users of cosmetic products that contain BZ3. Moreover, different undesirable effects have been attributed to this compound. Thus, sensitive analytical methods to monitor urinary excretion of this compound should be developed. This paper presents a selective and sensitive methodology for BZ3 determination at ultratrace levels in human urine samples. The methodology is based on a novel microextraction technique, known as single drop microextraction (SDME). An ionic liquid (IL) has been used as extractant phase instead of an organic solvent. After the microextraction process, the extractant phase was injected into a liquid chromatography system. The variables of interest in the SDME process were optimized using a multivariate optimization approach. A Plackett-Burman design for screening and a circumscribed central composite design for optimizing the significant variables were applied. Ionic strength, extraction time, stirring speed, pH, ionic liquid type, drop volume and sample volume were the variables studied. The optimum experimental conditions found were: sodium chloride concentration, 13% (w/v); extraction time, 25 min; stirring speed, 900 rpm; pH, 2; ionic liquid type, 1-hexyl-3-methylimidazolium hexafluorophosphate ([C(6)MIM][PF(6)]); drop volume, 5 microL; and sample volume, 10 mL. The proposed method requires a standard addition calibration approach, and it has been successfully employed to determine free BZ3 in urine samples coming from human volunteers who applied a sunscreen cosmetic containing this UV filter. The limit of detection was in the order of 1.3 ng mL(-1) and repeatability of the method, expressed as relative standard deviation, was 6% (n=8). PMID- 17720176 TI - Peptic digestion of beta-casein. Time course and fate of possible bioactive peptides. AB - Numerous peptides obtained by enzymatic digestion of food proteins have been reported to exhibit biological activities. In this study, the focus was placed on peptides of beta-casein from bovine milk after a gastro-analogous in vitro digestion with pepsin, a protease with broad specificity. In order to study the time course of the digestion, the process was stopped after specific times and the samples were subjected to HPLC separation followed by matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) and nanoelectrospray (nanoESI) quadrupole time-of-flight (qTOF) mass spectrometry. A combined sequencing approach using de novo interpretation and databases was employed. Overall, 100% of the beta-casein sequence was covered by identifying 125 peptides of 4-84 residues in length, including 3 phosphorylated species. The results show that the peptic hydrolysis starts at the C-terminus of the protein. The release of known bioactive peptides from beta-casein following the peptic digestion under simulated gastric conditions is unlikely with a few exceptions. Furthermore, an amino acid variation was found, providing evidence for the existence of an additional genetic variant of beta-casein. PMID- 17720177 TI - Comparative study of solvation parameter models accounting the effects of mobile phase composition in reversed-phase liquid chromatography. AB - Solvation parameter models relate linearly compound properties with five fundamental solute descriptors (excess molar refraction, dipolarity/polarizability, effective hydrogen-bond acidity and basicity, and McGowan volume). These models are widely used, due to the availability of protocols to obtain the descriptors, good performance, and general applicability. Several approaches to predict retention in reversed-phase liquid chromatography (RPLC) as a function of these descriptors and mobile phase composition are compared, assaying the performance with a set of 146 organic compounds of diverse nature, eluted with acetonitrile and methanol. The approaches are classified in two groups: those that only allow predictions of retention for the mobile phases used to build the models, and those valid at any other mobile phase composition. The first group includes the use of ratios between the regressed coefficients of the solvation models that are assumed to be characteristic for a column/solvent system, and the application of offsets to transfer the retention from a reference mobile phase to any other. Maximal accuracy in predictions corresponded, however, to the approaches in the second group, which were based on models that describe the retention as a function of mobile phase composition (expressed as the solvent volume fraction or a normalised polarity measurement), where the coefficients were made dependent on the solvent descriptors. The study revealed the properties that influence the retention and distinguish the particular behaviour of acetonitrile and methanol in RPLC. PMID- 17720179 TI - Amphiphilic copolymer grafted "smart surface" enhanced by surface roughness. AB - Polystyrene-poly(acrylic acid) (PS-PAA) block copolymers polymerized by atom transfer radical polymerization were covalently grafted to both smooth and microtextured surfaces. These amphiphilic copolymers were utilized to create smart surfaces, which can be responsive to external stimuli, e.g., pH values or organic solvent. Atom force microscopy, field emission scanning electron microscopy, and contact angle measurements were employed to investigate the physiochemical features of the copolymer brushes. It was found that the wettability of surfaces depended on both the PS/PAA molar ratio and external solvent properties. Hydrophilic surfaces were obtained after treatment with basic solution, as well as a polar solvent, such as ethanol. With treatment with acidic solution or toluene, the surface could be reversibly turned relatively hydrophobic, probably due to the rearrangement or reorganization of polymer chains. Moreover, rougher surfaces, which were microtextured by ZnO nanorods, were incorporated into this adaptive system to enhance the tunable range of wettability. PMID- 17720178 TI - Electrophoretic separation of large DNAs using steric confinement. AB - We report an alternative method for electrophoretic separation of large DNAs using steric confinement between solid walls, without gel or obstacles. The change of electrophoretic mobility vs confinement thickness is investigated using fluorescence video microscopy. We observe separation at small confinement thicknesses followed by a transition to the bulk behavior (no separation) at a thickness of about 4 mum (a few radii of gyration for the studied DNA chains). We present tentative explanations of our original observations. PMID- 17720180 TI - Ultrasonic attenuation spectroscopy of emulsions with droplet sizes greater than 10 microm. AB - Ultrasonic attenuation measurement is a frequently used tool for non-destructive determination of dispersion characteristics. Useful information like particle or droplet size and their concentration can be obtained, if the relation between size and attenuation of the dispersion is known. In this work, the theoretical model by Faran for the intermediate sound wave regime (IWR) is presented in combination with experimental data. In the IWR, the acoustic behavior is governed by elastic scattering rather than by dissipative effects. Experiments with emulsion of droplet sizes greater than 10 mum were carried out. Silicone oil, sunflower oil and olive oil were selected for the disperse phase of the oil-in water emulsions. First, emulsions having droplets in the micrometer range were created. Afterwords, attenuation measurements of different concentrated emulsion were carried out. Some adjustments reflecting concentration influence were performed to outline the agreement between calculations and measurements. The validity of the model can be confirmed, if the volume fraction of the disperse phase is considered as a variable. Finally, droplet size distributions from theoretical attenuation spectra could be calculated based on a log-normal distribution. PMID- 17720181 TI - Adsorption mechanism and dispersion efficiency of three anionic additives [poly(acrylic acid), poly(styrene sulfonate) and HEDP] on zinc oxide. AB - Adsorption on ZnO of sodium poly(acrylate) (PAA), sodium poly(styrene sulfonate) (PSS) and a monomer surfactant [hydroxyethylidene diphosphonate (HEDP)] was investigated in suspensions initially equilibrated at pH 7. Results demonstrate interplay in the adsorption mechanism between zinc complexation, salt precipitation, and ZnO dissolution. In the case of PAA, the adsorption isotherm exhibits a maximum attributed to the precipitation of zinc polyacrylate. PSS and HEDP formed high-affinity adsorption isotherms, but the plateau adsorption of HEDP was significantly lower than that of PSS. The adsorption isotherm of each additive is divided into two areas. At low additive concentration (high zinc/additive ratio), the total zinc concentration in the solution decreased and the pH increased upon addition. At a higher additive ratio, zinc concentration and pH increased with the organic concentration. The increase in pH is due to the displacement of hydroxyl ions from the surface and the increase in zinc concentration results from the dissolution of ZnO due to the complexation of zinc ions by the organics. The stability of the ZnO dispersions was investigated by measurement of the particle size distribution after addition of various amounts of polymers. The three additives stabilized the ZnO dispersions efficiently once full surface coverage was reached. PMID- 17720182 TI - The influence of the size of the hydrophilic group on the miscibility of zwitterionic and nonionic surfactants in mixed monolayers and micelles. AB - The aim of this work was to study the surface properties of nonionic and zwitterionic surfactants (namely dodecyl-beta-D-glucoside-DG, dodecyl-beta-D maltoside-DM, and dodecylsulfobetaine-DSB) and the miscibility of these compounds in mixed monolayers and micelles. A thermodynamic description of the interactions between surfactants in the mixed aggregates was provided by the Motomura theory. The obtained results indicate that the investigated compounds mix nonideally both in the mixed adsorbed layers and in micelles. The calculated values of the excess free energies of mixing prove that the interactions between molecules, in the mixed monolayers and micelles, are more attractive or less repulsive than those in the respective one-component aggregates. However, the values of the excess free energy of the components mixing in the monolayers and micelles are more negative for the DSB/DG system than for the DSB/DM system. This indicates that the investigated zwitterionic surfactant interacts more strongly with DG than with DM. This results from the difference in the size of the polar heads of nonionic surfactants. PMID- 17720183 TI - On the modified Tabor parameter for the JKR-DMT transition in the presence of a liquid meniscus. AB - The JKR, DMT, Maugis models and Tabor parameter for contact under normal loading have been developed based mainly on solid-solid (van der Waals) interactions. In this case, the characteristic length scale for the adhesive forces in the Tabor parameter is the equilibrium interatomic spacing. However, for contact in humid environments, where a liquid meniscus may be present, capillary forces with a longer force range related to the Kelvin radius dominate. Fogden and White [J. Colloid Interface Sci. 138 (1990) 414] introduced a parameter that includes the Kelvin radius for the JKR-DMT transition. This topic was also addressed by Maugis and Gauthier-Manuel [J. Adhes. Sci. Technol. 8 (1994) 1311] who included capillary effects within the frame work that Maugis had previously established. The parameters introduced by Fogden and White and Maugis and Gauthier-Manuel can be viewed as a modified Tabor parameter for the JKR-DMT transition. In the present work, the Kelvin equation linking the Kelvin radius and the relative humidity was explicitly included in the modified Tabor parameter. This provided a quantitative description of the JKR-DMT transition in terms of the relative humidity. This parameter was examined via load and contact radius measurements, where the latter were obtained from Bowden and Tabor's assumption that the friction force f=tauA. The friction experiments were conducted at two different humidity levels using a newly-developed mesoscale friction tester (MFT), which provides a very wide range of contact radii. The modified Tabor parameter was used to reexamine data from pull-off experiments in water and cyclohexane vapor environments [L.R. Fisher, J.N. Israelachvili, Colloids Surf. 3 (1981) 303 and H.K. Christenson, J. Colloid Interface Sci. 121 (1988) 170]. Finally, guidelines are presented for the appropriate choice of contact mechanics models to be used in interpreting data from SFA and AFM experiments in humid environments. PMID- 17720184 TI - Intracellular cytokine detection by flow cytometry in pigs: fixation, permeabilization and cell surface staining. AB - Intracellular flow cytometry is a method of cytokine detection that allows simultaneous detection of intracellular cytokines and cell surface markers. This important method is not extensively used in pigs, in particular due to the inaccessibility of proper methodological protocols modifying comprehensive human protocols. The aim of this study was to find the best procedure for fixation and permeabilization of porcine blood leukocytes and simultaneous cell surface staining. Permeabilization with commercial kits gave better results in most of the chosen parameters compared with combinations of different concentrations of paraformaldehyde and saponin. Among the commercial kits tested, the best results were obtained with the IntraStain kit. Cell surface markers were detected on cells stimulated for cytokine production by antibodies anti-CD14 (clone MIL-2), anti-SWC3, anti-CD4 and anti-CD8 except anti-CD14 (clone Tuk4). While anti-CD8 (clone MIL-12) must be used for staining of unfixed cells, the other antibodies recognize fixed and/or permeabilized cells. Moreover, anti-SWC3 and anti-CD14 (clone MIL-2) antibodies can stain cells during the permeabilization step. These modifications of the cell surface staining protocol allow the researcher to speed up the procedure of intracellular cytokine staining or to combine cell surface staining and intracellular cytokine staining. The present study can serve as a particular protocol of intracellular cytokine detection and as a suggestion for optimization of the fixation, permeabilization and cell surface staining procedure in any laboratory. PMID- 17720185 TI - Overt expression of AP-1 reduces alpha myosin heavy chain expression and contributes to heart failure from chronic volume overload. AB - Reduced expression of alpha-MHC plays a significant role in cardiac contractile dysfunction from hemodynamic overload. Previously, Pur proteins and YY1 have been shown to play a role in alpha-MHC repression during heart failure induced by pressure overload and by spontaneous hypertension, respectively. This was not observed in volume-overload-induced heart failure, suggesting additional regulatory mechanisms for alpha-MHC repression. The present study was performed to identify volume overload responsive transcription factors involved in alpha MHC gene regulation. DNA binding activity of several transcription factors was evaluated in a functionally characterized rat model of heart failure induced by aorto-caval shunt. After 10 weeks of shunt, severe LV dilatation and reduced LV function were accompanied by increased expression of ANF and beta-MHC, and decreased expression of alpha-MHC. This was associated with dramatic (10-fold) activation of AP-1 together with increased expression of c-fos and c-jun. AP-1 activation was not observed following 4 weeks of shunt when cardiac function was preserved. In cultured cardiomyocytes, induction of AP-1 by PMA attenuated alpha MHC mRNA by 60%. Transient transfection assays mapped PMA responsive sequence to 582 to -588 bp of alpha-MHC promoter. Deletion or mutation of these nucleotides had minimal effect on basal promoter activity but played a dominant role in PMA mediated repression of alpha-MHC promoter activity. Over-expression of c-fos and c-jun in cardiomyocytes inhibited alpha-MHC promoter activity in a concentration dependent manner. Data suggest a repressive role of AP-1 in alpha-MHC expression and its possible involvement in the transition from compensatory hypertrophy to heart failure in chronic volume overload. PMID- 17720187 TI - Increased apoptosis and myocyte enlargement with decreased cardiac mass; distinctive features of the aging male, but not female, monkey heart. AB - We studied gender-specific changes in aging cardiomyopathy in a primate model, Macaca fascicularis, free of the major human diseases, complicating the interpretation of data specific to aging in humans. Left ventricular (LV) weight/body weight decreased, p<0.05, in old males but did not change in old females. However, despite the decrease in LV weight, mean myocyte cross-sectional area in the old males increased by 51%. This increase in myocyte size was not uniform in old males, i.e., it was manifest in only 20-30% of all the myocytes from old males. In old males there was a 4-fold increase in frequency of myocyte apoptosis without any increase in proliferation-capable myocytes assessed by Ki 67 expression. Apoptosis was unchanged in old female monkey hearts, whereas the frequency of myocytes expressing Ki-67 declined 90%. These results, opposite to findings from rodent studies, indicate distinct differences in which male and female monkeys maintain functional heart mass during aging. The old male hearts demonstrated increased apoptosis, which more than offset the myocyte hypertrophy. Interestingly, the hypertrophy was not uniform and there was no significant increase in myocyte proliferation. PMID- 17720188 TI - A novel proteomic approach identifies new interaction partners for proliferating cell nuclear antigen. AB - During DNA replication and repair, many proteins bind to and dissociate in a highly specific and ordered manner from proliferating cell nuclear antigen (PCNA). We describe a combined approach of in silico searches at the genome level and combinatorial peptide synthesis to investigate the binding properties of hundreds of short PCNA-interacting peptides (PIP-peptides) to archaeal and eukaryal PCNAs. Biological relevance of our combined approach was demonstrated by identification an inactive complex of Pyrococcus abyssi ribonuclease HII with PCNA. Furthermore we show that PIP-peptides interact with PCNA largely in a sequence independent manner. Our experimental approach also identified many so far unidentified PCNA interacting peptides in a number of human proteins. PMID- 17720186 TI - Factors controlling cardiac myosin-isoform shift during hypertrophy and heart failure. AB - Myosin is a molecular motor, which interacts with actin to convert the energy from ATP hydrolysis into mechanical work. In cardiac myocytes, two myosin isoforms are expressed and their relative distribution changes in different developmental and pathophysiologic conditions of the heart. It has been realized for a long time that a shift in myosin isoforms plays a major role in regulating myocardial contractile activity. With the recent evidence implicating that alteration in myosin isoform ratio may be eventually beneficial for the treatment of a stressed heart, a new interest has developed to find out ways of controlling the myosin isoform shift. This article reviews the published data describing the role of myosin isoforms in the heart and highlighting the importance of various factors shown to influence myosin isofrom shift during physiology and disease states of the heart. PMID- 17720189 TI - Coevolution of a homing endonuclease and its host target sequence. AB - We have determined the specificity profile of the homing endonuclease I-AniI and compared it to the conservation of its host gene. Homing endonucleases are encoded within intervening sequences such as group I introns. They initiate the transfer of such elements by cleaving cognate alleles lacking the intron, leading to their transfer via homologous recombination. Each structural homing endonuclease family has arrived at an appropriate balance of specificity and fidelity that avoids toxicity while maximizing target recognition and invasiveness. I-AniI recognizes a strongly conserved target sequence in a host gene encoding apocytochrome B and has fine-tuned its specificity to correlate with wobble versus nonwobble positions across that sequence and to the amount of degeneracy inherent in individual codons. The physiological target site in the host gene is not the optimal substrate for recognition and cleavage: at least one target variant identified during a screen is bound more tightly and cleaved more rapidly. This is a result of the periodic cycle of intron homing, which at any time can present nonoptimal combinations of endonuclease specificity and insertion site sequences in a biological host. PMID- 17720191 TI - Vasopressin-neurophysin and DST in major depression: relationship with suicidal behavior. AB - The purpose of the present study was to assess if AVP-neurophysin is associated with hypercortisolemia and suicidal behaviour in depressed patients. The study included 28 patients subgrouped into suicide attempters (n=13) and nonattempters (n=15). We assessed basal AVP-neurophysins concentrations and post-dexamethasone (DST) cortisol levels. Concentrations of AVP-neurophysins did not differ between DST suppressors and nonsuppressors: 0.29+/-0.13 ng/ml vs 0.36+/-0.21 ng/ml, (F=1.1, df=1, 27, p=0.30). Suicide attempters did not differ from nonattempters for AVP-neurophysins levels. Our results fail to support a role of AVP in the early cortisol escape. PMID- 17720190 TI - The putative DNA-binding protein Sto12a from the thermoacidophilic archaeon Sulfolobus tokodaii contains intrachain and interchain disulfide bonds. AB - The Sto12a protein, from the thermoacidophilic archaeon Sulfolobus tokodaii, has been identified as a small putative DNA-binding protein. Most of the proteins with a high level of amino acid sequence homology to this protein are derived from members of the Sulfolobaceae family, including a transcriptional regulator. We determined the crystal structure of Sto12a at 2.05 A resolution by multiple wavelength anomalous dispersion phasing from the selenomethionine-containing protein crystal. This is the first structure of a member of this family of DNA binding proteins. The Sto12a protein forms a homodimer, and the structure is composed of an N-terminal alpha-helix, a winged-helix-turn-helix domain, and a C terminal alpha-helix that forms an interchain antiparallel coiled coil. The two winged-helix domains are located at both ends of the coiled coil, with putative DNA-recognition helices separated by approximately 34 A. A structural homology search indicated that the winged-helix domain shared a high level of homology with those found in B-DNA- or Z-DNA-binding proteins from various species, including archaea, bacteria, and human, despite a low level of sequence similarity. The unique structural features of the Sto12a protein include intrachain and interchain disulfide bonds, which stabilize the chain and homodimer structures. There are three cysteine residues: Cys15 and Cys16 in the N terminal alpha-helix, and Cys100 in the C-terminal alpha-helix. Cys15 is involved in an interchain disulfide bridge with the other Cys15, and Cys16 forms an intrachain disulfide bridge with Cys100. This is a novel fold among winged-helix DNA-binding proteins. Possible DNA-binding interactions of the Sto12a protein are discussed based on the crystal structure of Sto12a and comparisons to other winged-helix DNA-binding proteins. PMID- 17720192 TI - Patterns of physician and patient rated quality of life during antipsychotic treatment in outpatients with schizophrenia. AB - Quality of life (QoL) in patients with schizophrenia has been assessed both from physician and patient perspectives, but little is known about agreement between these perspectives and predictors of agreement. The aim of this study was to analyze a large sample of patients with schizophrenia to discover patterns of physician and patient-rated QoL in patients with schizophrenia and identify predictors for these patterns. This study (EASE) was designed to investigate the QoL and subjective well-being in out-patients with schizophrenia during antipsychotic treatment in a naturalistic setting. Assessments were carried out at baseline and at 3, 6, 9 and 12 months, using the quality of life scale (QLS) and the subjective well-being on neuroleptics scale (SWN-K). A hierarchical cluster analysis was used to define groups of patients based on the SWN-K and QLS total scores at all visits. 1174 patients were included in the cluster analyses that were based on SWN-K and QLS total scores over time. Four distinct clusters were identified: patients with: (1) continuously high QoL (23.2%), (2) continuously moderate QoL (45.8%), (3) continuously low QoL (11.2%), and (4) improving QoL (19.9%). Clusters 1-3 were stable in terms of QoL, whilst cluster 4 changed towards improvement. Various predictors for the four clusters were identified. In the cluster with improving QoL, the absence of treatment with an oral conventional antipsychotic pre-study and no medication change due to lack of efficacy at baseline were predictors for improvement. In the cluster with continuously high QoL, no medication change due to lack of efficacy and lowest CGI-S scores at baseline were predictors. Oral conventional antipsychotic treatment pre-study was predictive for the cluster with continuously moderate QoL. In the cluster with continuously low QoL, medication change due to lack of efficacy and highest CGI-S scores were predictors. These findings suggest that various factors may predict whether a patient with schizophrenia experiences a continuously high QoL, a continuously moderate QoL, a continuously low QoL, or improving QoL whilst on antipsychotic treatment. PMID- 17720193 TI - Tracking of green fluorescent protein labeled Escherichia coli confirms bacterial translocation in blind loop rat. AB - BACKGROUND: Previous investigators have documented small intestinal mucosal injury in blind loop rats. However, the definitive evidence of intestinal bacterial translocation in blind loop animals has been lacking. The purpose of this study was to confirm bacterial translocation in blind loop rats and to evaluate the preventive effect of glutamine on bacterial translocation caused by blind loops. MATERIALS AND METHODS: Escherichia coli TG1 labeled with green fluorescent protein was used to track bacterial translocation by gavage to rats. Six groups (n = 10) of rats were studied: unoperated control rats; rats with self emptying blind loop; rats with self-filling blind loop; unoperated control rats treated with glutamine, 400 mg/d; rats with self-emptying blind loop treated with glutamine, 400 mg/d; rats with self-filling blind loop treated with glutamine, 400 mg/d. Representative tissue specimens of the mesenteric lymph nodes, liver, spleen, and kidney were aseptically harvested for bacteria culture. RESULTS: Bacteria were detected in extraintestinal organs of rats with self-emptying blind loop, self-filling blind loop, and self-filling blind loop treated with glutamine. By fluorescence microscope and XbaI restriction digestion analysis, we elucidated that the bacteria isolated from extraintestinal organs were the same bacteria we gavaged to the rats. CONCLUSION: We confirmed bacterial translocation in self-filling blind loop and self-emptying blind loop rats. In addition, we also showed that glutamine prevents bacterial translocation in self-emptying blind loop rats. PMID- 17720194 TI - Extracorporeal shock wave enhanced extended skin flap tissue survival via increase of topical blood perfusion and associated with suppression of tissue pro inflammation. AB - OBJECTIVE: Distal skin flap ischemic necrosis is a significant challenge in reconstructive surgery. This study assessed whether extracorporeal shock wave (ESW) treatment rescues compromised flap tissue by enhancing tissue perfusion and is associated with suppression of inflammatory response. METHODS: This study used the dorsal skin random flap model in a rodent. Thirty-six male Sprague Dawley rats were divided into three groups. Group I, a control group, received no treatment. Group II was administrated 500 impulses of ESW treatment at 0.15 mJ/mm(2) as a single treatment immediately postoperatively. Group III received 500 impulses of ESW at 0.15 mJ/mm(2) applied immediately postoperatively and the day following surgery. Flap blood perfusion was detected by laser Doppler. Flap survival/necrosis area and histological staining of flap ischemia zone was performed on day 7 postoperatively. The tumor necrosis factor alpha, vascular endothelial growth factor, and proliferating cell nuclear antigen expression were evaluated with immunohistochemical staining. RESULTS: Experimental results indicated that the necrotic area of the flaps in Group II was significantly reduced compared with that in the control group (13 +/- 2.6% versus 42 +/- 5.7%, P < 0.01). There was small and insignificant reduction in the necrotic area in Group III compared with the controls. Flap tissue blood perfusion was significantly increased postoperatively in Group II. Histological staining indicated that ESW treatment substantially increased vascular endothelial growth factor and proliferating cell nuclear antigen expressions, reduced leukocyte infiltration, and suppression of tumor necrosis factor alpha expression in flap tissue ischemic zones in Group II compared with that in controls. CONCLUSION: Optimal dosage of ESW treatment has a positive effect in rescuing ischemic zone of flap by increasing tissue perfusion and is associated with suppressing inflammatory response. PMID- 17720195 TI - New aspects of Helicobacter pylori infection involvement in gastric oncogenesis. AB - Gastric adenocarcinoma not located in the cardia still remains second only to lung cancer as the leading cause of cancer-related mortality worldwide, whereas adenocarcinoma of the cardia and gastroesophageal junction has been rapidly rising over the past two decades. Gastric malignancy can be subdivided into diffuse and intestinal pathologic entities that have different epidemiological and prognostic features. Various genetic and environmental factors lead to either abnormal gene overexpression or inappropriate expression of normal genes, whose products confer the malignant phenotype. Advances have been made in genetic changes mostly of the intestinal type; its development is probably a multistep process, as has been well described in colon carcinogenesis. Oncogene overexpression, tumor suppressor loss, and defective DNA mismatch repair is associated with gastric cancer. The most common genetic abnormalities tend to be loss of heterozygosity of particularly tumor suppressor p53 gene or "adenomatous polyposis coli" gene. The latter leads to gastric carcinogenesis through changes related to E-cadherin-catenin complex, which plays a critical role in normal tissue architecture maintenance. Mutation of any of its components results in loss of cell-cell adhesion, thereby contributing to malignancy. Putative trophic factors have also been involved in gastric oncogenesis. E-cadherin/CDH1 gene germline mutations have been recognized in families with an inherited predisposition to diffuse-type malignancy. This review focuses mainly on Helicobacter pylori infection involved in gastric carcinogenesis through various mechanisms, including repopulation of the stomach with bone marrow-derived stem cells that may facilitate gastric cancer progression, thereby necessitating eradication of this bacterium. PMID- 17720196 TI - Up-regulation of interleukin-10 mRNA expression in peripheral leukocytes predicts poor outcome and diminished human leukocyte antigen-DR expression on monocytes in septic patients. AB - BACKGROUND: None of the parameters can predict the deterioration of sepsis early enough. A new predictor allowing earlier detection of changes in septic patients' condition is indispensable. METHODS: We examined whether cytokine-related mRNA expression in peripheral leukocytes, cytokine blood level, and monocyte human leukocyte antigen (HLA)-DR expression rate could be useful predictors of deterioration of sepsis. Twenty septic patients were enrolled. mRNA expression levels were quantified using real-time reverse transcriptase-polymerase chain reaction and assessed by percent changes during the first 24 h. Cytokine blood levels on admission and day 3 and monocyte HLA-DR expression rate on day 3 were also measured. Correlations between each of these parameters, and between these parameters and outcome were analyzed. RESULTS: Among seven kinds of cytokines studied, only IL-10 mRNA level showed significant difference between survivors and non-survivors (P < 0.05). Mortality rate of interleukin (IL)-10 mRNA level up regulated group was significantly higher than that of IL-10 mRNA level down regulated group (P < 0.05). HLA-DR expression rate in non-survivors were significantly lower than that in survivors (P < 0.05). Although IL-10 blood level on day 3 significantly correlated with HLA-DR expression on day 3(r = 0.54, P < 0.05), IL-10 blood level on admission did not correlate with it. Contrarily, the degree of up-regulation of IL-10 mRNA expression during the first 24 h significantly correlated with the degree of diminished HLA-DR expression on day 3 (r = 0.78, P < 0.001). CONCLUSIONS: Up-regulated IL-10 mRNA expression and diminished HLA-DR expression could be indicators of poor outcome. Furthermore, IL 10 mRNA expression measurement could predict the onset of immunoparalysis indicated by diminished HLA-DR expression earlier than IL-10 blood level measurement, leading to earlier commencement of the treatment. PMID- 17720198 TI - Spinocerebellar ataxia type 7 mimicking Kearns-Sayre syndrome: a clinical diagnosis is desirable. AB - Spinocerebellar ataxias are a group of autosomal dominant cerebellar degenerative disorders, which are characterized by clinical and genetic variability. Spinocerebellar ataxia type 7 (SCA7) is less variable in clinical presentation than other SCAs. We present a pediatric patient with 13 and 70 trinucleotide CAG repeats within SCA7 gene and no family history, whose presentation mimicked Kearns-Sayre syndrome (KSS). We review the differential diagnosis of cerebellar ataxia with vision loss secondary to retinal pigmentary dystrophy. This paper supports concept of a desirable clinical diagnosis to avoid multiple genetic or invasive testing in children with neurodegenerative disorders. PMID- 17720197 TI - Development of PTH eluting microspheres for the treatment of hypoparathyroidism. AB - BACKGROUND: Parathyroid hormone (PTH) replacement has been demonstrated to be superior to conventional treatment with calcium supplementation and vitamin D analogs for the treatment of hypoparathyroidism. In this investigation we evaluated the feasibility of using PTH microsphere encapsulation as a potential delivery system for PTH. MATERIALS AND METHODS: Using the spontaneous emulsion technique, PTH microspheres were created by encapsulating PTH (1-34) in a copolymer of polyglycolic and polylactic acid (PLGA). Additional microspheres were constructed by coencapsulating calmodulin with PTH (1-34) in the PLGA microspheres. Microsphere production was confirmed using electron microscopy. PTH release was measured in vitro using an enzyme-linked immunosorbent assay. The bioactivity of PTH released from the microspheres was confirmed in vivo using a hypoparathyroid rat model by measuring serum calcium concentrations before and 3 h after subcutaneous injection of PTH microspheres. RESULTS: PTH microsphere and PTH/calmodulin microspheres could be created using the spontaneous emulsion technique. Physiologically significant PTH release was measured in vitro for 20 days. PTH release was calcium sensitive and exhibited negative feedback. This effect was augmented by coencapsulation with calmodulin. PTH released from the microspheres caused a significant rise in serum calcium levels from an average of 6.35 (6.19-6.48 mg/dL) to 8.55 mg/dL (8.22-8.73). PTH released from the PTH/calmodulin microspheres resulted in an increase in serum calcium from a mean of 6.8 (6.7-6.9 mg/dL) to 8.1 mg/dL (7.8-8.2). CONCLUSIONS: The PLGA microspheres can be used to provide calcium sensitive controlled release of biologically active PTH and offer a potential mean of providing biomimetic hormone replacement therapy. PMID- 17720199 TI - Spontaneous obliteration of MRI-silent cerebral angiomatosis revealed by CT angiography in a patient with Sturge-Weber syndrome. AB - Type I Sturge-Weber syndrome (SWS) is a neurocutaneous syndrome characterized by facial port wine stain and ipsilateral leptomeningeal angiomatosis. It is commonly complicated by glaucoma and neurological disturbances including seizures, hemiparesis, transient stroke-like deficits, and behavioral problems. Gadolinium-enhanced MRI is the study of choice for demonstrating the leptomeningeal angiomatosis, and is particularly useful for making the diagnosis. Cerebral hematoma and spontaneous obliteration of cerebral angiomatosis have never been reported in SWS. We describe a patient with type I SWS in which a hemorrhage in the left temporal lobe was caused by an underlying angiomatosis. No arteriovenous malformations were detected by brain CT or gadolinium-enhanced MRI, whereas a small angiomatous nidus draining into an ectasic venous collector near the hematoma was disclosed by brain CT angiography. Carotid angiography, performed 3 years after the hemorrhage, demonstrated the spontaneous obliteration of the angioma. This description expands the phenotypic spectrum of type I SWS in which the occurrence of cerebral hemorrhage and MRI-silent cerebral angiomatosis should be included, and emphasizes the need of performing a brain CT angiography in SWS patients whose routine neuroimaging studies fail to detect potentially harmful vessel malformation. PMID- 17720200 TI - Depletion of mitochondrial DNA in leukocytes of patients with poly-Q diseases. AB - Polyglutamine (poly-Q) diseases are late-onset neurodegenerative disorders arising from the expansion of an unstable CAG repeat in the affected gene, which is translated to a tract of glutamine residues. This kind of mutant proteins may be aggregated and accumulated, and thereby enhance cellular oxidative stress. In one of our previous studies (Free Radic. Res. 2003;37:1307-17), we found that alteration in the leukocyte mtDNA content is very sensitive to the level of oxidative stress in blood. Thus, we proposed that leukocyte mtDNA content may be used as a biomarker to predict the severity of clinical manifestation of poly-Q diseases. We recruited 50 healthy subjects and 114 patients with poly-Q diseases, including spinal cerebellar atrophy 2/3, spinal bulbar muscular atrophy, and Huntington chorea. We found that mtDNA in leukocytes was depleted in patients with poly-Q diseases (P<0.05). Moreover, the results showed that patients with lower mtDNA content more frequently manifested multiple-symptom disorders and had high CAG repeat numbers in the mutant genes. In conclusion, we suggest that leukocyte mtDNA content correlates with the length of GAG repeat and may serve as an index of the severity of poly-Q diseases. PMID- 17720201 TI - Carbon monoxide intoxication: an updated review. AB - Carbon monoxide (CO), a highly toxic gas produced by incomplete combustion of hydrocarbons, is a relatively common cause of human injury. Human toxicity is often overlooked because CO is tasteless and odorless and its clinical symptoms and signs are non specific. The brain and the heart may be severely affected after CO exposure with carboxyhemoglobin (COHb) levels exceeding 20%. Damage occurs because the affinity of hemoglobin for CO is 210 times higher than for O(2). Hypoxic brain damage predominates in the cerebral cortex, cerebral white matter and basal ganglia, especially in the globus pallidus. Diagnosis requires clinical acumen and a high index of suspicion, combined with epidemiological data, clinical examination, analysis of ambient air CO and patient COHb levels; also required are cardiology evaluation including ECG as well as neurological evaluation including brain imaging (CT and/or MRI, MR spectroscopy), and neuropsychological testing. Although immediate O(2) breathing is sometimes an adequate treatment, hyperbaric oxygen therapy (HBO) is favored. Subsequently, only symptomatic therapy is available for the long-term sequelae of CO poisoning. PMID- 17720202 TI - Clinical correlates of phosphene perception in migraine without aura: an Asian study. AB - INTRODUCTION: Although controversy exists with regard to the presence of hypoexcitability versus hyperexcitability of the visual cortex in migraine patients, there remain a group who do not perceive phosphenes (P-). However, its clinical implications have not been systematically addressed. In this study, we hypothesize that P- patients classified as migraine without aura (MO) have distinct clinical features. METHODS: Twenty-nine Asian MO patients (7 men; mean age: 44; median: 45; range: 25 to 65) were consecutively entered into the study. Visual cortex transcranial magnetic stimulation (TMS) was performed in the migraine interictum. RESULTS: Of the 19 patients, 19 (66%) were able to perceive phosphenes (P+), while 10 (34%) were not able to after repeated TMS (P-). P- patients had significantly higher headache frequency (p=0.008) and pain score (p=0.002) compared with P+ patients. In addition, there was significant positive correlation of phosphene threshold with pain score (r=0.52, p=0.02) in P+ patients. There was no significant difference between P+ and P- patients in terms of age (t-test, p=0.6). CONCLUSIONS: Our study is inkeeping with the hypothesis that interictal visual cortex excitability is reduced in relation to the severity of migraine in Asian MO patients, and lack of phosphene perception may be related to significantly elevated thresholds beyond the output of TMS stimulators. PMID- 17720203 TI - Uncertainty in allometric exponent estimation: a case study in scaling metabolic rate with body mass. AB - Many factors could influence the allometric scaling exponent beta estimation, but have not been explored systematically. We investigated the influences of three factors on the estimate of beta based on a data set of 626 species of basal metabolic rate and mass in mammals. The influence of sampling error was tested by re-sampling with different sample sizes using a Monte Carlo method. Small random errors were introduced to measured data to examine their influence on parameter estimations. The influence of analysis method was also evaluated by applying nonlinear and linear regressions to the original data. Results showed that a relative large sample size was required to lower statistical inference errors. When sample size n was 10% of the base population size (n=63), 35% of the samples supported beta=2/3, 39% supported beta=3/4, and 15% rejected beta=0.711, even though the base population had a beta=0.711. The controversy surrounding the estimation of beta in the literature could be partially attributable to such small sample sizes in many studies. Measurement errors in body mass and base metabolic rate, especially in body mass, could largely increase alpha and beta errors. Analysis methods also affected parameter estimations. Nonlinear regressions provided better estimates of the scaling exponent that were significantly higher than these commonly estimated by linear regressions. This study demonstrated the importance of the quantity and quality of data as well as analysis method in power law analysis, raising caution in interpreting power law results. Meta-data synthesis using data from independent studies seems to be a proper approach in the future, but caution should be taken to make sure that such measurements are made using similar protocols. PMID- 17720204 TI - A thermodynamic perspective on food webs: quantifying entropy production within detrital-based ecosystems. AB - Because ecosystems fit so nicely the framework of a "dissipative system", a better integration of thermodynamic and ecological perspectives could benefit the quantitative analysis of ecosystems. One obstacle is that traditional food web models are solely based upon the principles of mass and energy conservation, while the theory of non-equilibrium thermodynamics principally focuses on the concept of entropy. To properly cast classical food web models within a thermodynamic framework, one requires a proper quantification of the entropy production that accompanies resource processing of the food web. Here we present such a procedure, which emphasizes a rigorous definition of thermodynamic concepts (e.g. thermodynamic gradient, disequilibrium distance, entropy production, physical environment) and their correct translation into ecological terms. Our analysis provides a generic way to assess the thermodynamic operation of a food web: all information on resource processing is condensed into a single resource processing constant. By varying this constant, one can investigate the range of possible food web behavior within a given fixed physical environment. To illustrate the concepts and methods, we apply our analysis to a very simple example ecosystem: the detrital-based food web of marine sediments. We examine whether entropy production maximization has any ecological relevance in terms of food web functioning. PMID- 17720205 TI - DNA repair deficiency and BPDE-induced chromosomal alterations in CHO cells. AB - The induction of chromosomal aberrations and sister chromatid exchanges by BPDE was evaluated in parental and different DNA repair deficient Chinese hamster ovary cell lines in order to elucidate the mechanisms involved in their induction. These included the parental line (AA8), nucleotide excision repair (UV4, UV5, UV61), base excision repair (EM9), homologous recombination repair (Irs1SF) and non-homologous end joining (V3-3) deficient ones. The ranking of different cell lines for BPDE-induced chromosome aberrations was: UV4, Irs1SF, UV5, UV 61, EM9, V3-3, and AA8 in a descending order. Cells deficient in NER and HRR were found to be very sensitive, indicating the importance of these pathways in the repair of lesions induced by BPDE. For induction of SCEs, HRR and BER deficient cells were refractory, whereas the other cell lines responded with a dose-dependent increase. The possible mechanisms involved in BPDE-induced chromosomal alterations are discussed. PMID- 17720206 TI - Effects of adolescent nicotine and SR 147778 (Surinabant) administration on food intake, somatic growth and metabolic parameters in rats. AB - Tobacco smoking and obesity are worldwide important health problems with a growing impact in adolescent and young adults. One of the consequences of nicotine withdrawal is an increase in body weight that can act as a risk factor to relapse. Experimental therapies with a cannabinoid receptor antagonist have been recently proposed for both cigarette smoking and complicated overweight. In the present study, we aimed to investigate metabolic and hormonal effects of chronic nicotine treatment (during treatment and in abstinence) in an animal model of adolescence as well as to address the pharmacological effects of the novel selective CB1 cannabinoid receptor antagonist, SR 147778 (Surinabant). Adolescence (postnatal days 37-44) and/or post-adolescence (postnatal days 45-59) administration of Surinabant reduced body weight gain, as well as plasma glucose levels and triglycerides. The drug also reduced insulin and leptin secretion, and increased adiponectin and corticosterone levels. The effects showed sexual dimorphisms and, in general, were more pronounced in females. Chronic exposure to nicotine (0.8 mg/kg), from postnatal days 30-44 did not result in overt effects on food intake or body weight gain. However, it altered certain responses to the administration of Surinabant, both when the two drugs were given simultaneously and when Surinabant was administered during the post-adolescence period, along nicotine withdrawal. The present results indicate that the endogenous cannabinoid system is active as a metabolic modulator during adolescence and that nicotine exposure can induce long-lasting effects on metabolic regulation, altering cannabinoid modulation of energy expenditure and metabolism. PMID- 17720207 TI - General justifications for public health regulation. AB - Convention holds that government intervention designed to promote population health and well-being is an unmitigated good. However, government should justify interventions because, almost invariably, they intrude on individual rights and interests and incur economic costs. This paper presents three general justifications for government intervention: (1) risk to others; (2) protection of incompetent people; and (3) risk to self. The first justification is the standard, well-accepted idea that government may intervene to prevent harm to others or punish individuals for inflicting harm. The second justification supports government action to protect the health and safety of those who are incapable of safeguarding their own interests. The third justification, and by far the most controversial, is paternalism; the protection of the health or safety of competent individuals irrespective of their own expressed wants or desires. This paper argues that the government gains the greatest legitimacy when regulating for the protection of harms to others, but even paternalism can support state action when health risks are socially embedded and harmful to the public. PMID- 17720208 TI - Pharmacokinetic study of an injectable long-acting parenteral formulation of doxycycline hyclate in calves. AB - Doxycycline hyclate (DOX-h) can be regarded as a time-dependant antibacterial. Hence, a parenteral long-acting formulation may be regarded as more pharmacologically sound. A poloxamer-based matrix was used to produce a long acting injectable preparation (DOX-h-LA) and its serum concentrations vs. time profile investigated after its s.c. injection to calves. Serum concentrations profiles for such a prepartion were compared to the corresponding profiles obtained with an aqueous formulation of DOX-h injected either i.m. or i.v. in 10 calves in a crossover study at dose of 10mg/kg, with washout periods. DOX-h-LA showed the greatest values for bioavailability (602%); maximum serum concentration (C(max)) value was 1.99microg/mL with a time to reach C(max) (T(max)) of 25h and an elimination half-life of 40.81h. Considering minimum effective serum concentration of 0.5microg/mL a dose-interval of 80h can be achieved for DOX-h-LA, and only 9.7h and 17h after the i.v. or i.m. administration of DOX-h, respectively. PMID- 17720209 TI - Calcium dependent and independent cytokine synthesis by air pollution particle exposed human bronchial epithelial cells. AB - Exposure to ambient air pollution particles with a diameter of <10 microm (PM(10)) has been associated with increased cardiopulmonary morbidity and mortality. We have shown that human bronchial epithelial cells (HBECs) exposed to PM(10) produce pro-inflammatory mediators that contribute to a local and systemic inflammatory response. Changes in intracellular calcium concentrations ([Ca(2+)](i)) have been demonstrated to regulate several functions of the airway epithelium including the production of pro-inflammatory mediators. The aim of the present study was to determine the nature and mechanism of calcium responses induced by PM(10) in HBECs and its relationship to cytokine synthesis. METHODS: Primary HBECs were exposed to urban air pollution particles (EHC-93) and [Ca(2+)](i) responses were measured using the fluoroprobe (Fura-2). Cytokine levels were measured at mRNA and protein levels using real-time PCR and ELISA. RESULTS: PM(10) increased [Ca(2+)](i) in a dose-dependent manner. This calcium response was reduced by blocking the influx of calcium into cells (i.e. calcium free medium, NiCl(2), LaCl(3)). PM(10) also decreased the activity of calcium pumps. PM(10) increased the production of IL-1beta, IL-8, GM-CSF and LIF. Preincubation with intracellular calcium chelator (BAPTA-AM) attenuated IL-1beta and IL-8 production, but not GM-CSF and LIF production. CONCLUSION: We conclude that exposure to PM(10) induces an increase in cytosolic calcium and cytokine production in bronchial epithelial cells. Our results also suggest that PM(10) induces the production of pro-inflammatory mediators via either intracellular calcium-dependent (IL-1beta, IL-8) or -independent (GM-CSF, LIF) pathways. PMID- 17720210 TI - Effects of dimethylarsinic and dimethylarsinous acid on evoked synaptic potentials in hippocampal slices of young and adult rats. AB - In this study, the effects of pentavalent dimethylarsinic acid ((CH(3))(2)AsO(OH); DMA(V)) and trivalent dimethylarsinous acid ((CH(3))(2)As(OH); DMA(III)) on synaptic transmission generated by the excitatory Schaffer collateral-CA1 synapse were tested in hippocampal slices of young (14-21 day-old) and adult (2-4 month-old) rats. Both compounds were applied in concentrations of 1 to 100 micromol/l. DMA(V) had no effect on the amplitudes of evoked fEPSPs or the induction of LTP recorded from the CA1 dendritic region either in adult or in young rats. However, application of DMA(III) significantly reduced the amplitudes of evoked fEPSPs in a concentration-dependent manner with a total depression following application of 100 micromol/l DMA(III) in adult and 10 micromol/l DMA(III) in young rats. Moreover, DMA(III) significantly affected the LTP-induction. Application of 10 micromol/l DMA(III) resulted in a complete failure of the postsynaptic potentiation of the fEPSP amplitudes in slices taken both from adult and young rats. The depressant effect was not reversible after a 30-min washout of the DMA(III). In slices of young rats, the depressant effects of DMA(III) were more pronounced than in those taken from adult ones. Compared to the (absent) effect of DMA(V) on synaptic transmission, the trivalent compound possesses a considerably higher neurotoxic potential. PMID- 17720211 TI - Nanomechanical probing of microbubbles using the atomic force microscope. AB - Atomic force microscopy (AFM) is a versatile mechanical nanosensor that can be used to quantify the mechanical properties of microbubbles (MBs) and the adhesion mechanisms of targeted MBs. Mechanical properties were investigated using AFM tipless cantilevers to microcompress the MBs. The range of compressive stiffness for biSphere was found to be between 1 and 10Nm(-1) using a cantilever with a spring constant of 0.6 Nm(-1). This stiffness was shown to decrease with the MB size in a non-linear fashion. It is also possible to calculate a theoretical Young's modulus of the shell. The adhesion properties of targeted lipid based MBs that use avidin-biotin chemistry for the attachment of targeting ligands were also studied. The MBs were attached to poly-L-lysine treated tipless cantilevers with spring constants ranging from 0.03 to 0.1 Nm(-1). This system interrogated individual cells with pulling cantilever distance of 15 microm, and scan rate at 0.2 Hz. The depth of contact was not larger than 0.4 microm. The targeted MBs provided a significantly larger adhesion to the cells compared to control ones. Average adhesion force was dependent on depth of contact. Analysis of the data demonstrated a single distribution of adhesion events with median at 89 pN, which is in agreement with the literature for such interactions. The nanointerrogation of MBs using AFM provides new insight into their mechanical properties, and should be of assistance to MB design and manufacture. PMID- 17720212 TI - Effect of membrane character and solution chemistry on microfiltration performance. AB - To help understand and predict the role of natural organic matter (NOM) in the fouling of low-pressure membranes, experiments were carried out with an apparatus that incorporates automatic backwashing and long filtration runs. Three hollow fibre membranes of varying character were included in the study, and the filtration of two different surface waters was compared. The hydrophilic membrane had greater flux recovery after backwashing than the hydrophobic membranes, but the efficiency of backwashing decreased at extended filtration times. NOM concentration of these waters (7.9 and 9.1mg/L) had little effect on the flux of the membranes at extended filtration times, as backwashing of the membrane restored the flux to similar values regardless of the NOM concentration. The solution pH also had little effect at extended filtration times. The backwashing efficiency of the hydrophilic membrane was dramatically different for the two waters, and the presence of colloid NOM alone could not explain these differences. It is proposed that colloidal NOM forms a filter cake on the surface of the membranes and that small molecular weight organics that have an adsorption peak at 220nm but not 254nm were responsible for "gluing" the colloids to the membrane surface. Alum coagulation improved membrane performance in all instances, and this was suggested to be because coagulation reduced the concentration of "glue" that holds the organic colloids to the membrane surface. PMID- 17720213 TI - Phyto-remediation potential of Ipomoea aquatica for Cr(VI) mitigation. AB - Phyto-remedial efficiency of Ipomoea aquatica was examined at different experimental conditions for a period of 3 months. This plant was selected due to its easy establishment, tolerance and growing easiness. In all trials, the I. aquatica was grown in coir dust to ensure an inert medium. Essential growth nutrients were supplied externally using Albert solution. Once plant growth conditions were fixed, the model system was spiked with Cr(VI) solution in the range of 7-90 ppm. Up to 28 ppm Cr(VI), I. aquatica exhibits uniform absorption characteristics showing over 75% removal of added Cr(VI). At this stage I. aquatica was not affected and it showed no toxicity symptoms. Therefore, it is suited as a potential phyto-remediant. Further I. aquatica is a vegetable particularly in Asian region; therefore caution has to be taken when selecting it for human consumption due to its high chromium accumulation capacity. PMID- 17720214 TI - Dietary exposure to dioxin-like compounds in three age groups: results from the Flemish environment and health study. AB - Lipophilic contaminants are present in the environment and bioaccumulate in the food chain. Therefore, their intake via animal fat of various sources was assessed for three age groups of the Flemish population, participating in a large biomonitoring program of the Flemish government. In total, 1636 adolescents (14 15 years), 1186 mothers (18-44 years), and 1586 adults (50-65 years) participated in the study and completed a semi quantitative food frequency questionnaire. Individual consumption data were combined, via a so-called simple distribution approach, with recent data on polychlorinated dibenzo-p-dioxins/furans and dioxin like polychlorinated biphenyls, measured via the chemical-activated luciferase gene expression (CALUX) bio-assay in food items available on the Flemish market. The median (95th percentile) estimated intakes of dioxin-like contaminants were 2.24 (4.61), 2.09 (4.26), and 1.74 (3.53) pg CALUX-TEQ kg(-1) bw d(-1) for, respectively adolescents, mothers and adults. These data are in the same range as those found in other European studies. The CALUX-TEQ results of respectively 59.8%, 53.7% and 36.2% of the adolescent, mother and adult population exceed the tolerable weekly intake (TWI) of 14 pg WHO-TEQ kg(-1) bw w(-1), as derived by the Scientific Committee on Food [Scientific Committee on Food, 2001. Opinion of the Scientific Committee on Food on the Risk Assessment of Dioxins and Dioxin-like PCBs in Food, CS/CNTM/DIOXIN/20 final Brussels, Belgium]. The main contributors of dioxin-like substances are fish and seafood (25-43% of the total intake), added fats (22-25% of the total intake) and dairy products (17-20% of the total intake). PMID- 17720215 TI - The accumulation of nonylphenol in a wastewater recycling process. AB - A mathematical model was developed in this paper to describe the nonylphenol (NP) accumulation in the effluent of a wastewater recycling system. The model quantitatively presented the relationships among the NP concentrations in the raw wastewater and the system effluent, the number of wastewater recycling cycles, the water recycling ratio, the system NP removal efficiency, and the NP accumulation factor. The mathematical model was then verified through experimental modeling of a wastewater recycling process, and it was indicated that the Pearson correlation coefficient between mathematical simulation and experimental modeling results was 0.652. The study results indicated that the NP accumulation factor of a wastewater recycling system would approach a constant for large number of wastewater recycling cycles given the wastewater recycling ratio and system NP removal efficiency. The results also revealed that the NP concentration in the effluent increased with the wastewater recycling ratio given the system NP removal efficiency, and the increase of NP removal efficiency would decrease the NP accumulation in the system effluent under a given wastewater recycling ratio condition. The model was then applied to compute the maximum wastewater recycling ratio, predict reclaimed water quality and direct the design and management of sewage recycling systems in China. PMID- 17720216 TI - Iron-induced decomposition of perfluorohexanesulfonate in sub- and supercritical water. AB - Decomposition of perfluorohexanesulfonate (PFHS), a bioaccumulative analogue of perfluorooctanesulfonate (PFOS), in sub- and supercritical water was investigated. Although PFHS was only slightly reactive in pure subcritical water at 350 degrees C, it decomposed to F(-) and SO(4)(2-) ions when the temperature was increased to 380 degrees C, at which temperature the water became supercritical state. Addition of zerovalent iron to the reaction system dramatically accelerated PFHS decomposition to F(-) ions in both sub- and supercritical water: for example, when the initial PFHS concentration was 741microM, the F(-) yields at 350 degrees C were 4.13-16.0 times as high as those in the absence of iron, depending on the amount and the particle size of the iron powder. After the reactions, small amounts of CO(2) and CF(3)H were also detected in the gas phase; these increased with temperature, and the amount of CF(3)H increased markedly when the reaction was carried out in supercritical water. Increasing the specific surface area of the iron powder markedly increased PFHS consumption and F(-) formation in the aqueous phase, which indicates that the reactions occurred on the iron surface and that the increased specific surface area was a key factor in accelerating the decomposition of PFHS to F(-) ions. PMID- 17720217 TI - Bio-reduction of N-nitrosodimethylamine (NDMA) using a hydrogen-based membrane biofilm reactor. AB - N-Nitrosodimethylamine (NDMA) is a disinfection by-product shown to be carcinogenic, mutagenic, and teratogenic. A feasible detoxification pathway for NDMA is a three-step bio-reduction that leads to ammonia and dimethylamine. This study examines the bio-reduction of NDMA in a H2-based membrane biofilm reactor (MBfR) that also is active in nitrate and sulfate reductions. In particular, the study investigates the effects of H2 availability and the relative loadings of NDMA, nitrate, and sulfate, which potentially are competing electron acceptors. The results demonstrate that NDMA was bio-reduced to a major extent (i.e., at least 96%) in a H2-based MBfR in which the electron-equivalent fluxes from H2 oxidation were dominated by nitrate and sulfate reductions. NDMA reduction kinetics responded to NDMA concentration, H2 pressure, and the presence of competing acceptors. The most important factor controlling NDMA-reduction kinetics was the H2 availability, controlled primarily by the H2 pressure, and secondarily by competition from nitrate reduction. PMID- 17720218 TI - Maternal transfer of organochlorine compounds to oocytes in wild and farmed gilthead sea bream (Sparus aurata). AB - To investigate the transfer of lipophilic organochlorine compounds to the gonads in gilthead sea bream females, liver and oocytes from wild and farmed females, just before spawning, were analysed by gas chromatography coupled to tandem mass spectrometry after clean-up of the fatty extracts by normal phase HPLC. This analytical methodology allowed us to achieve limits of detection of around 0.1 ng/g. Data obtained show that the chemicals studied are transferred from the liver to oocytes in ratios up to 0.51. In general this means that less than a half of pollutant load is transferred from liver to oocytes. A significant correlation (p<0.05) between log K(ow) and ratios (oocytes/liver) was found. Compounds with larger Log K(ow) present lower lipid-based concentration ratios (oocytes/liver). We have inferred that the reason the fugacity model is not accomplished is specifically dependent on the vitellogenesis process, which involves the transfer of lipids from the liver to oocytes in teleostei. No significant differences (t-Student) have been found between wild and farmed females transfer ratios (oocytes/liver). PMID- 17720219 TI - The PCDD/F and PBDD/F pollution in the ambient atmosphere of Shanghai, China. AB - Rapid economic growth in the last two decades in Shanghai has had a great adverse influence on its air quality. Therefore, the atmospheric pollutants of Shanghai have received much concern. In this study, concentrations of 2,3,7,8-substituted PCDD/Fs and PBDD/Fs congeners were measured in the ambient air of four districts in Shanghai. The mean atmospheric concentrations (TEQs) of total 2,3,7,8-PCDD/Fs and 2,3,7,8-PBDD/Fs were 8031 fg m(-3) (497.1 fg I-TEQ m(-3)) and 1358 fg m(-3) (304.1 fg I-TEQ m(-3)) for Jiading District, 5308 fg m(-3) (289.0 fg I-TEQ m(-3)) and 709 fg m(-3) (146.9 fg I-TEQ m(-3)) for Zhabei District, 4014 fg m(-3) (144.4 fg I-TEQ m(-3)) and 1239 fg m(-3) (256.9 fg I-TEQ m(-3)) for Pudong District, 3348 fg m(-3) (143.2 fg I-TEQ m(-3)) and 699 fg m(-3) (148.4 fg I-TEQ m(-3)) for Huangpu District, respectively. Our results showed that almost all the PCDD/Fs and PBDD/Fs congeners were partitioned into the particulate phase except the lower chlorinated or brominated ones. The logarithm of the gas/particle partitioning coefficient K(p) has good linear correlation with that of the sub cooled vapor pressure p(L). Concentrations of PCDD/Fs and PBDD/Fs were both positively correlated to elemental carbon in all districts except Pudong District, suggesting elemental carbon could be a good indicator for dioxins' air pollution. It is intensively suggested that more detailed and deeper studies about PBDD/Fs should be carried out due to their relatively high atmospheric concentrations in Shanghai. PMID- 17720220 TI - Development of supercritical carbon dioxide extraction with a solid phase trap for dioxins in soils and sediments. AB - A method involving supercritical fluid extraction (SFE) with a solid phase trap containing activated alumina was investigated for the rapid analysis of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin like polychlorinated biphenyls (DL-PCBs) in soils and sediments. The samples were extracted by using supercritical carbon dioxide with water (2% versus CO(2) flow velocity) being used as an entrainer at a pressure of 30 MPa and a temperature of 130 degrees C for 50 min. The extracts were adsorbed on an activated alumina trap that was maintained at a temperature of 150 degrees C, and then, PCDD/DFs and DL-PCBs were eluted with 20 ml of hexane at 60 degrees C. After concentration, they were measured with a high-resolution gas chromatograph interfaced to a high-resolution mass spectrometric detector. The average concentrations of PCDD/DFs and DL-PCBs corresponded to the results obtained by the conventional method, and the reproducibility of this SFE method was below 21% of the relative standard deviations for all samples. The total time required for the analysis of the pretreatment of this method was only 2 h. PMID- 17720221 TI - Exchange pattern of gaseous elemental mercury in an active urban landfill facility. AB - The environmental behavior of gaseous elemental mercury (Hg) in the ambient air was investigated from the center of a municipal landfill site (area approximately 0.6km(2)) located in Dae Gu, Korea in the winter of 2004. In order to provide insight on the Hg exchange processes in strong source areas, we continuously analyzed Hg concentration gradients developed across two heights between 1m and 5m over soil surfaces at hourly intervals. The results displayed Hg concentrations in the lower and upper levels in the range of 1.46-13.1ngm(-3) (3.33+/-1.29ngm(-3): N=139) and 1.20-13.7ngm(-3) (3.27+/-1.23ngm(-3): N=139), respectively. The results of our analysis, when divided separately into emission and dry deposition, showed that emission of Hg was fairly dominant in frequency (up to 58%) over dry deposition. By multiplying our Hg gradient data with the K values predicted indirectly from the results of previous studies, the emission and deposition fluxes of Hg were estimated as 39.0+/-43.3ngm(-2)h(-1) (N=80) and 60.0+/-80.2ngm(-2)h(-1) (N=59), respectively. Although the magnitudes of exchange were moderately lower than previously investigated anthropogenic sources, the overall results of this study suggest that an active landfill site can act as an important source of Hg in an urban environment along with other man-made activities. PMID- 17720222 TI - Some issues relating to the use of perfluorooctanesulfonate (PFOS) samples as reference standards. AB - Samples of potassium perfluorooctanesulfonate (PFOSK) from three suppliers were analyzed by LC-ESI-MS/MS for purity and by LC-ESI-MS for the percentage of linear isomer present. Our data indicated that the purity ranged from 80% to 98% and the percentages of linear isomer from 67% to 79%. The proportion of branched isomers present in the samples was also estimated using (19)F NMR. These results agreed quite closely with those found by LC-ESI-MS indicating that there is essentially no difference in overall SIM response factor for the branched isomers vs. that of the linear isomer. Several further observations relevant to the use of standards when analyzing for PFOS were encountered during this study. It appears unlikely that matrix effects attributable to the cation (sodium or potassium) present in PFOSNa or PFOSK internal standards is an issue. In seeking potential matrix effects, it was found that the chromatography was improved substantially when the standard was injected as a solution in 80:20 methanol/water rather than 100% methanol. Notably, in concert with the improvement in chromatography, an increase of about 10% in response was observed. In some closely related studies, when (18)O(2) mass-labeled perfluorohexanesulfonate was used as an internal standard, the actual and theoretical concentration ratios matched closely those for related native sulfonates as long as they did not co-elute. However, when they did co elute, the peak intensities of the native species were enhanced by about 5%, while those of the labeled compound were suppressed by a similar amount. If this effect were not taken into account, the concentration of the native would be inflated by 10%. PMID- 17720223 TI - Five more arguments to invalidate the passive scavenging version of the carnivore hominid-carnivore model: a reply to Blumenschine et al. (2007a). PMID- 17720224 TI - The endurance running hypothesis and hunting and scavenging in savanna-woodlands. PMID- 17720225 TI - Horizontal and vertical variability of mercury species in pore water and sediments in small lakes in Ontario. AB - Mary Lake, St. George Lake, and Philips Lake are located in the Greater Toronto Area, Ontario, Canada. These lakes are relatively small and have no direct inflow and outflow channels. Mercury (Hg) input to the lakes comes mainly from atmospheric deposition. Sediment cores from the points of the maximum lake depth and surface sediment samples from the points of maximum lake depth to the bank of each lake were collected in October 2005. Total and methyl mercury concentrations in the pore water and sediments of these samples were determined. In these small lakes with high organic content, there was no correlation between organic content and total mercury (THg) in the samples throughout the entire sediment cores while strong positive correlation between these two parameters was observed in all the surface sediments. Compared with typical methylmercury (MeHg) depth-profiles of sediment cores in other studies, where MeHg concentrations and methylation rates decreased sharply with increasing depth, MeHg distributions in the sediment cores in this study showed that MeHg might have been produced not only in the upper sediment but also in the deeper sediments, which resulted in a larger MeHg reservoir in the sediment. Organic matter, to some extent, affected MeHg distributions in the samples throughout the entire sediment cores. Concentrations of MeHg in all the surface sediments, however, were not controlled by organic matter, whereas they were largely a function of water column depths. Total mercury concentrations in pore water were relatively homogenous in both the sediment cores and surface sediment while MeHg in pore water generally deceased with increasing depth in the sediment cores and increasing distance from the centre of the lakes in surface sediments. Methylmercury contributed 1% to 76% of THg in the pore water samples. Concentrations and distributions of MeHg in overlying water and sediment-surface water in Mary Lake and St. George Lake suggested that both in situ production of MeHg in lake water and the release of MeHg from sediment contributed to high MeHg in deep anoxic water. PMID- 17720226 TI - Spatial and temporal variation in size of polar bear (Ursus maritimus) sexual organs and its use in pollution and climate change studies. AB - Sexual organs and their development are susceptible to atmospheric transported environmental xenoendocrine pollutants and climate change (food availability). We therefore investigated sexual organs from 55 male and 44 female East Greenland polar bears (Ursus maritimus) to obtain information about growth/size and sexual maturity. Then, the genitalia size was compared with those previously reported from Canadian and Svalbard polar bears. Growth models showed that East Greenland male polar bears reached sexual maturity around 7 years of age and females around 4 years of age. When comparing East Greenland and Svalbard polar bears, the size of baculum and uterus were significantly lower in the East Greenland polar bears (ANOVA: all p < 0.05). Based on previously published baculum mean values from Canadian polar bears, a similar baculum pattern was found for East Greenland vs. Canadian polar bears. It is speculated whether this could be a result of the general high variation in polar bear body size, temporal distribution patterns of anthropogenic long-range transported persistent organic pollutants or climate change (decreasing food availability). The present investigation represents conservation and background data for future spatial and temporal assessments of hunting, pollution and climate change scenarios. PMID- 17720227 TI - Infective endocarditis associated with spondylodiscitis and frequent secondary epidural abscess. AB - BACKGROUND: Although many patients with IE complain of joint, muscle, and back pain, infections at these sights are rare. Indeed, in patients with back pain and endocarditis, less than 4% actually demonstrate spondylodiscitis. CASE DESCRIPTION: We recently encountered 4 patients with this complication, one each caused by Staphylococcus aureus, Streptococcus bovis, Streptococcus mitis, and Enterococcus faecalis, and wondered whether the nature of the infecting organism determined the development of spondylodiscitis and epidural abscess. In a literature review, 36 patients with endocarditis and spondylodiscitis were identified. Only 9 (25%) were caused by Streptococcus viridans and the remainder by staphylococci, enterococci, and other streptococci. Usually more than 50% of all cases of IE were caused by Streptococcus viridans, although more recent studies would indicate an incidence of about 40%. CONCLUSION: We conclude that spondylodiscitis with epidural abscess is more likely to occur in those patients with endocarditis who are infected by organisms with pyogenic potential. PMID- 17720228 TI - "Migration" of traumatic subarachnoid hematoma? A case report. AB - BACKGROUND: Traumatic spinal SAH with neurologic deficits is rare and easily misdiagnosed, especially after traumatic intracranial hemorrhage. CASE DESCRIPTION: We report a case of spinal SAH with root compression occurring after a scooter accident. CONCLUSIONS: Physicians should be aware of descending migration of intracranial SAH as a possible cause of spinal cord or root compression, especially in the patient with late onset spinal symptoms. PMID- 17720232 TI - A comparison of urinary complications following total laparoscopic radical hysterectomy and laparoscopic pelvic lymphadenectomy to open abdominal surgery. AB - OBJECTIVE: The objective of this study was to compare total laparoscopic radical hysterectomy (TLRH) and laparoscopic pelvic lymphadenectomy (LPS) to total abdominal radical hysterectomy (TARH) and pelvic lymphadenectomy (LPT) in terms of urinary tract lesions and postoperative urinary retention. METHODS: Starting in 2004, we treated all early stage cervical cancer patients with TLRH and LPS. The control group for this analysis was a historical cohort of patients treated with TARH+LPT. Within the TLRH+LPS group, we assessed whether the width of parametrial tissue removed was a risk factor for urinary tract injuries or postoperative urinary retention. RESULTS: Fifty women were included in the TLRH+LPS group and forty-eight were included in the TARH+LPT group. There were no conversions from laparoscopy to laparotomy. There was no statistically significant difference in intraoperative urinary complications between the groups. Four (8%) intraoperative urinary tract injuries in the LPS (3 cystotomies and 1 ureteral lesions all repaired laparoscopically) and 2 (4.2%) in the LPT group (2 cystotomies) occurred (p=0.68). Similarly, there was no statistically significant difference in postoperative urinary complications between groups. Urinary postoperative complications were: 1 (2%) ureterovaginal and 1 vesicovaginal fistulas, 1 delayed ureteric fistula in LPS group vs. 0 in LPT group (p=0.24). Urinary retention was complained by 7 (14%) and 7 (14.6%) patients in LPS and LPT groups respectively (p=1.00). The average width of parametrial tissue removed in the LPS group was 32.2+14.0 mm in patients with vs. 39.5+13.6 mm in patients without urinary complications (p=0.11). CONCLUSIONS: A laparoscopic approach is comparable to the laparotomy in terms of urinary lesions and postoperative retention. The width of parametrium removed does not affect the risk of urinary lesions or postoperative retention. PMID- 17720233 TI - Novel cytotoxic agents from an unexpected source: bile acids and ovarian tumor apoptosis. AB - OBJECTIVE: Unique biologic activities have been identified for the 4 different bile acids: cholic acid (CA, chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), and ursodeoxycholic acid (UDCA). The aim of this study was to examine and compare the effects of these 4 bile acids on the human ovarian cancer cell lines A2780 and A2780-CP-R(cisplatin-resistant) and to evaluate mechanisms of action. METHODS: Antiproliferative effects were determined by the cytotoxic MTT assay. Cells undergoing apoptosis were identified by morphologic analysis of cells stained using Diff-Quick and nuclear staining with DAPI and by quantitative nucleosome ELISA assay. Cells were lysed in buffer after 24 h of exposure to three different concentrations of bile acid (50 mM, 200 mM, and 400 mM) and protein concentrations were determined. Cell extracts containing 25 mg of protein were assayed for protein kinase C (PKC) enzyme activity. RESULTS: None of the bile acids stimulated proliferation of ovarian cancer cells. CA and UDCA had only minimal cytotoxic effect even at maximum concentrations. In contrast, DCA and CDCA administration resulted in statistically significant dose-dependent cytotoxicity in both platinum sensitive and platinum-resistant cell lines (p<0.05). Cells incubated with DCA and CDCA exhibited morphologic features characteristic of apoptosis. The quantitative nucleosome ELISA assay demonstrated over 10 times increased nucleosome levels after cells were treated for 24 h by DCA and CDCA at 200 mM and 400 mM as compared to CA or UDCA treatment and to untreated controls (p<0.01). All 4 bile acids reduced PKC activity at concentrations of 200 and 400 mM (p<0.01). CONCLUSIONS: CDCA and DCA have significant cytotoxic activity in ovarian cancer cells via induction of apoptosis. The mechanism of apoptosis appears to be mediated by alternative kinases distinct from PKC. CDCA and DCA may have clinical utility in the treatment of ovarian cancer pending in vivo confirmation of activity especially in cisplatin-resistant disease. PMID- 17720234 TI - Ovarian volumes among women with endometrial carcinoma: associations with risk factors and serum hormones. AB - OBJECTIVES: Data suggest that post-menopausal women with larger ovaries are at increased risk for endometrial carcinoma; however, analyses comparing ovarian volume to serum hormone levels are limited. Accordingly, we assessed ovarian volumes in relation to serum sex hormone levels among post-menopausal women with endometrial carcinoma who participated in a multi-center case-control study. METHODS: Data for established risk and protective factors for endometrial carcinoma were collected via in-person interviews. Ovarian volumes were estimated from pathology reports. Associations between exposures and age-adjusted ovarian volumes were analyzed for 175 cases with available data. For a subset of 135 cases, we analyzed relationships between ovarian volume, adjusted for age and body mass index (BMI), and serum hormone levels by analysis of variance. RESULTS: Ovarian volume declined progressively from 1.83 cm3 among women ages 55-59 years to 1.23 cm3 among women age 70 years or older (p-trend=0.02). Larger ovarian volume was associated with early menarche (p-trend=0.03), having given birth (p=0.01), and weakly with elevated BMI (p-trend=0.06). After adjustment, increased ovarian volume was associated with higher estradiol (p-trend=0.007); albumin-bound estradiol (p-trend=0.01); and free estradiol (p-trend=0.006) levels; androstenedione, estrone and estrone sulfate showed similar, though non significant associations. CONCLUSIONS: Among women with endometrial carcinoma, larger ovaries were associated with higher serum levels of estrogens. Further studies examining the role of the ovaries in post-menopausal hormonal carcinogenesis are warranted. PMID- 17720235 TI - Role for estradiol in female-typical brain and behavioral sexual differentiation. AB - The importance of estrogens in controlling brain and behavioral sexual differentiation in female rodents is an unresolved issue in the field of behavioral neuroendocrinology. Whereas, the current dogma states that the female brain develops independently of estradiol, many studies have hinted at possible roles of estrogen in female sexual differentiation. Accordingly, it has been proposed that alpha-fetoprotein, a fetal plasma protein that binds estrogens with high affinity, has more than a neuroprotective role and specifically delivers estrogens to target brain cells to ensure female differentiation. Here, we review new results obtained in aromatase and alpha-fetoprotein knockout mice showing that estrogens can have both feminizing and defeminizing effects on the developing neural mechanisms that control sexual behavior. We propose that the defeminizing action of estradiol normally occurs prenatally in males and is avoided in fetal females because of the protective actions of alpha-fetoprotein, whereas the feminizing action of estradiol normally occurs postnatally in genetic females. PMID- 17720237 TI - Assessing mediation: the necessity of theoretical considerations. PMID- 17720236 TI - A critical role for Pin1 in allergic pulmonary eosinophilia in rats. AB - BACKGROUND: Infiltration, accumulation, and degranulation of eosinophils in the lung are hallmarks of active allergic asthma. The pulmonary response to inhaled allergen triggers the secretion of eosinophil chemoattractants and antiapoptotic cytokines, including GM-CSF, IL-3, IL-4, IL-5, and eotaxin, among others. We recently showed that in vitro Pin1 regulated eosinophil production of and response to GM-CSF. OBJECTIVE: We sought to determine the effect of Pin1 inhibition on pulmonary eosinophilia after allergen challenge. METHODS: The Pin1 inhibitor juglone (5-hydroxy-1,4-naphthoquinone) was administered to allergen sensitized and allergen-challenged Brown Norway rats. Bronchoalveolar lavage fluid and lungs were assessed for inflammation, cytokine expression, and Pin1 activity. RESULTS: Juglone-treated rats showed a dramatic reduction (approximately 75%) in bronchoalveolar lavage fluid and pulmonary eosinophilia but no change in lymphocyte, monocyte/macrophage, or neutrophil numbers. GM-CSF and IL-5 expression were also significantly reduced, whereas Pin1-independent cytokines, such as eotaxin or IL-4, as well as housekeeping mRNAs and proteins, including actin, were unaffected by juglone. The eosinophils present in the lung in juglone-treated rats showed significantly greater apoptosis. CONCLUSION: These data suggest that in vivo Pin1 blockade attenuates GM-CSF and IL-5 production and can selectively reduce eosinophilic allergic inflammation. CLINICAL IMPLICATIONS: Eosinophils can be selectively reduced by Pin1 blockade, despite allergen challenge. PMID- 17720238 TI - Wear of ceramic and antagonist--a systematic evaluation of influencing factors in vitro. AB - OBJECTIVE: (1) To systematically review the existing literature on in vitro assessments of antagonist wear of ceramic materials; (2) To systematically evaluate possible influencing factors on material and antagonist wear of ceramic specimens. METHODS: The database MEDLINE was searched with the terms "enamel," "wear" and "antagonist." The selected studies were analyzed with regard to wear parameters, type of antagonist and outcome. In the laboratory study, three ceramic materials were selected with different compositions and physical properties: IPS d.SIGN low-fusing metal ceramic, IPS Empress leucite ceramic, e.max Press lithium disilicate ceramic. These materials were subjected to the Ivoclar wear method (Willytec chewing simulator, 120,000cycles, 5kg weight) by systematically modifying the following variables which resulted in 36 tests with 8 specimens in each group: (1) configuration (flat, crown specimen), (2) surface treatment (polish, glaze), (3) type of antagonist (ceramic, two types of enamel stylus). Furthermore, the enamel styluses were cut to measure the enamel thickness and cusp width. Wear of both the material and the antagonist was quantified by scanning plaster replicas of the specimens with a laser scanner (etkon es1) and matching baseline and follow-up data with the Match 3D software (Willytec). The data were log-transformed to stabilize the variance and achieve near normality. To test the influence of specific test parameters, a four-way ANOVA with post hoc tests and Bonferroni correction was applied. RESULTS: The systematic review revealed 20 in vitro studies in which a material and the antagonist wear of the same material was examined. However, the results were inconsistent mainly due to the fact that the test parameters differed widely. Most studies used prepared enamel from extracted molars as the antagonist and flat polished ceramic specimens. The test chamber was filled with water and some sort of sliding movement was integrated in the wear generating process. However, there was a huge variation in relation to the applied force, the used force actuator, the number of cycles, and the frequency of cycles per time as well as the number of specimens. The results of the systematic laboratory tests revealed that the following factors strongly influence the wear: configuration (more material wear of flat versus crown specimens), surface treatment (more antagonist wear of glazed versus polished specimens), the antagonist system (more material wear and less antagonist wear for ceramic stylus versus enamel stylus), and enamel thickness (less wear for thicker enamel). Material wear was not very much different between the materials. However, e.max Press generally caused more antagonist wear than the other two materials, which were quite similar. However, the main influencing factors did not yield consistent results for all the subgroups and there was a huge variability of results within the subgroups especially in those groups that used enamel as antagonist. SIGNIFICANCE: As far as consistency and correlation with clinical studies is concerned, the set-up that consists of unprepared enamel of molar cusps against glazed crowns seems to be the most appropriate method to evaluate a ceramic material with regard to antagonist wear. However, due to the high variability of results large sample sizes are necessary to differentiate between materials, which calls the whole in vitro approach into question. PMID- 17720239 TI - The effect of hyaluronic acid incorporation on fibroblast spreading and proliferation within PEG-diacrylate based semi-interpenetrating networks. AB - The nanometer-scale mesh size of many synthetic crosslinked hydrogel networks restricts encapsulated cells to a rounded morphology that can inhibit cellular processes such as proliferation and migration that are essential for the early stages of remodeling and tissue formation. The objective of these studies was to investigate an approach for accelerating cellular remodeling based on the creation of semi-interpenetrating networks (IPNs) composed of hydrolytically degradable poly(ethylene glycol) (PEG) diacrylate macromers and native, enzymatically degradable extracellular matrix (ECM) components (collagen, gelatin and hyaluronic acid (HA)). Among the three ECM components investigated, addition of HA at concentrations of 0.12% w/v and greater supported fibroblast spreading throughout the three-dimensional network and significantly increased proliferation relative to control hydrogels without HA. Incorporation of HA resulted in relatively small changes in hydrogel physical/chemical properties such as swelling, degradation rate, and elastic modulus. Fibroblast spreading was eliminated by the addition of hyaluronidase inhibitors, demonstrating that cell mediated enzymatic degradation of HA is a necessary mechanism responsible for the observed increases in fibroblast activity. By accelerating early cellular remodeling and growth, these semi-IPNs may be useful vehicles for cell transplantation in a variety of tissue engineering applications. PMID- 17720240 TI - The mechanical properties of the skin epidermis in relation to targeted gene and drug delivery. AB - A challenge in combating many major diseases is breaching the skin's tough outer layer (the stratum corneum (SC)) and delivering drugs and genes into the underlying abundant immunologically sensitive viable epidermal cells with safe, practical physical technologies. To achieve this effectively and accurately, design information is needed on key skin mechanical properties when pushing into and through epidermal skin cells. We measure these important mechanical properties by penetrating through the intact SC and viable epidermis (VE) of freshly excised murine skin with a NANO-indenter, using custom tungsten probes fabricated with nominally 5 and 2 microm diameters (with nanoscale tips). We show the skin Young's modulus, storage modulus and stress all dramatically decreased through the SC. Also, for a given penetration depth, decreasing the probe size significantly increases the storage modulus. Biological variation in penetrating the skin was shown. These collective findings advance the rational design of physical approaches for delivering genes and drugs within key cells of the VE. PMID- 17720241 TI - Systematic study of osteoblast response to nanotopography by means of nanoparticle-density gradients. AB - Features over a wide range of length scales affect the biological response to a surface. While the influence of micro-features has been extensively studied, the effect of nano-features has only rarely been systematically investigated. We have developed a simple method to produce nano-featured gradients by kinetically controlled adsorption of negatively charged silica nanoparticles onto positively charged, poly(ethylene imine) (PEI)-coated silicon wafers. Subsequent sintering of the particles allowed a tuning of the particle morphology and resulted in a firm anchoring of the particles to the surface. Particle-density gradients were characterized by atomic force microscopy (AFM). Cell experiments with rat calvarial osteoblasts (RCO) on nano-featured gradients exhibited a significant decrease in proliferation at locations with higher particle coverage. Seven days post seeding, the number of osteoblasts was eight times higher at positions without particles compared to positions with maximum particle coverage. While cells spread well and developed a well-organized actin network in the absence of particles, spreading and formation of a strong actin network was considerably hindered at locations with maximum particle density. PMID- 17720242 TI - Controlled formation of magnetite crystal by partial oxidation of ferrous hydroxide in the presence of recombinant magnetotactic bacterial protein Mms6. AB - Mms6 is a small acidic protein that is tightly associated with bacterial magnetite in Magnetospirillum magneticum AMB-1. This protein has previously shown iron binding activity, allowing it to generate uniform magnetic crystals by co precipitation of ferrous and ferric ions. Here, magnetite crystals were formed by the partial oxidation of ferrous hydroxide in the presence and absence of Mms6. The crystals synthesised were systematically characterised according to their sizes and morphologies using high-resolution transmission electron microscopy. Mms6-mediated synthesis of magnetite by this methods produced crystals of a uniform size and narrow size distribution with a cubo-octahedral morphology, similar to bacterial magnetite observed in M. magneticum AMB-1. The crystals formed in the absence of Mms6 were octahedral, larger with an increased size distribution. Protein quantification analysis of Mms6 in the synthesised particles indicated tight association of this protein onto the crystal. Furthermore, high affinities to iron ions and a highly charged electrostatic quality suggest that the protein acts as a template for the nucleus formation and/or acts as a growth regulator by recognising crystal faces. The method introduced in this study presents an alternative route for controlling the size and shape of magnetite crystals without the use of organic solvent and high temperatures. PMID- 17720243 TI - Analysis of gene expression profile of TPM3-ALK positive anaplastic large cell lymphoma reveals overlapping and unique patterns with that of NPM-ALK positive anaplastic large cell lymphoma. AB - Anaplastic large cell lymphoma (ALCL) comprises a group of non-Hodgkin lymphomas characterized by the expression of the CD30/Ki-1 antigen. A subset of ALCL is characterized by chromosomal translocations involving the anaplastic lymphoma kinase (ALK) gene on chromosome 2. While the most common translocation is the t(2;5)(p23;q35) involving the nucleophosmin (NPM) gene on chromosome 5, up to 12 other translocations partners of the ALK gene have been identified. One of these is the t(1;2)(q25;p23) which results in the formation of the chimeric protein TPM3-ALK. While several of the signaling pathways induced by NPM-ALK have been elucidated, those involved in ALCLs harboring TPM3-ALK are largely unknown. In order to investigate the expression profiles of ALCLs carrying the NPM-ALK and TPM3-ALK fusions, we carried out cDNA microarray analysis of two ALCL tissue samples, one expressing the NPM-ALK fusion protein and the other the TPM3-ALK fusion protein. RNA was extracted from snap-frozen tissues, labeled with fluorescent dyes and analyzed using cDNAs microarray containing approximately 9,200 genes and expressed sequence tags (ESTs). Quantitative fluorescence RT-PCR was performed to validate the cDNA microarray data on nine selected gene targets. Our results show a significant overlap of genes deregulated in the NPM-ALK and TPM-ALK positive lymphomas. These deregulated genes are involved in diverse cellular functions, such as cell cycle regulation, apoptosis, proliferation, and adhesion. Interestingly, a subset of the genes was distinct in their expression pattern in the two types of lymphomas. More importantly, many genes that were not previously associated with ALK positive lymphomas were identified. Our results demonstrate the overlapping and unique transcriptional patterns associated with the NPM-ALK and TPM3-ALK fusions in ALCL. PMID- 17720244 TI - Importance of the leader region of mRNA for translation initiation of ColE2 Rep protein. AB - Translation initiation of mRNA encoding the Rep protein of the ColE2 plasmid required for initiation of plasmid DNA replication is fairly efficient in Escherichia coli cells despite the absence of a canonical Shine-Dalgarno sequence. To define sequences and structural elements responsible for translation efficiency of the Rep mRNA, a series of rep-lacZalpha translational fusions bearing various mutations in the region encoding the leader region of the Rep mRNA was generated and tested for the translation activity by measuring the beta galactosidase activity. We showed that the region rich in A and U between the stem-loop II structure and GA cluster sequence, formation of the stem-loop II structure, but not its sequence, and the region between the GA cluster sequence and initiation codon are important along with the GA cluster sequence for efficient translation of the Rep protein. The existence of these important regions in the leader region of the Rep mRNA may explain the mechanism of inhibition of the Rep protein translation by an antisense RNA (RNAI), which is complementary to the leader region. PMID- 17720245 TI - Human and bovine respiratory syncytial virus vaccine research and development. AB - Human (HRSV) and bovine (BRSV) respiratory syncytial viruses (RSV) are two closely related viruses, which are the most important causative agents of respiratory tract infections of young children and calves, respectively. BRSV vaccines have been available for nearly 2 decades. They probably have reduced the prevalence of RSV infection but their efficacy needs improvement. In contrast, despite decades of research, there is no currently licensed vaccine for the prevention of HRSV disease. Development of a HRSV vaccine for infants has been hindered by the lack of a relevant animal model that develops disease, the need to immunize immunologically immature young infants, the difficulty for live vaccines to find the right balance between attenuation and immunogenicity, and the risk of vaccine-associated disease. During the past 15 years, intensive research into a HRSV vaccine has yielded vaccine candidates, which have been evaluated in animal models and, for some of them, in clinical trials in humans. Recent formulations have focused on subunit vaccines with specific CD4+ Th-1 immune response-activating adjuvants and on genetically engineered live attenuated vaccines. It is likely that different HRSV vaccines and/or combinations of vaccines used sequentially will be needed for the various populations at risk. This review discusses the recent advances in RSV vaccine development. PMID- 17720246 TI - Effects of chronic low-dose acrylamide exposure on progressive ratio performance in adolescent rats. AB - Acrylamide (ACR) is a neurotoxicant known to produce peripheral neuropathy in rats and humans, but little is known of its potential for producing cognitive or motivational alterations. Chronic exposure to low doses of ACR as a food contaminant is known to occur widely in humans. This research evaluated the effects of daily ACR exposure on food-motivated behavior, with exposures beginning prenatally on gestation day 6 and continuing through approximately postnatal day (PND) 85. Plug-positive Fischer 344 dams (9-10 per dose) were gavaged daily with 0, 0.1, 0.3, 1.0 or 5.0mg/kg/day ACR. On PNDs 1-22, pups were gavaged with the same dose their dam had received. On PND 22, pups were weaned and pair-housed with a same-sex littermate and ACR exposure continued at 0, 1, 3, 10 and 50ppm via drinking water. One male and one female pup per litter were tested in an operant chamber under a progressive ratio (PR) schedule of food reinforcement from approximately 6 to 12 weeks of age. Results over 6 weeks of testing indicated a significant treatment effect of ACR on number of reinforcers earned, with Tukey HSD post hoc tests revealing significantly fewer reinforcers earned in the 5.0mg/kg/day dose group than in controls. A significant effect of ACR on response rate was also observed, with the Tukey HSD post hoc tests revealing a significantly lower response rate in the 5.0mg/kg/day group than in controls. No effects of ACR were observed on post-reinforcement pause. These data suggest that daily ACR exposure at 5.0mg/kg/day can produce measurable decrements on aspects of food-motivated behavior. PMID- 17720247 TI - Forskolin potentiates the paraoxon-induced hyperexcitability in snail neurons by blocking afterhyperpolarization. AB - One characteristic of organophosphate poisoning is the ability to increase excitability or induce epileptiform activity in nerve cells, but underlying mechanisms are not fully understood. We have previously reported that paraoxon, an organophosphate compound, at submicromolar concentrations effectively suppress Ca(2+) spikes and modulate the activity of snail neurons. This effect was unrelated to acetylcholinesterase (AChE) inhibition but was found to involve the direct or indirect modulation of ion channels [Vatanparast J, Janahmadi M, Asgari AR, Sepehri H, Haeri-Rohani A. Paraoxon suppresses Ca(2+) spike and afterhyperpolarization in snail neurons: relevance to the hyperexcitability induction. Brain Res 2006a;1083(1):110-7]. In the present study, the interaction of paraoxon with cAMP formation on the modulation of Ca(2+) spikes and neuronal excitability was examined. Forskolin, the activators of adenylate cyclase, suppressed afterhyperpolarization (AHP) and increased the activity of snail neurons without any significant effect on the Ca(2+) spike duration. Pretreatment with forskolin, although attenuated the suppressing effect of paraoxon on the duration of Ca(2+) spikes but also potentiated the paraoxon-induced hyperexcitability by enhancing the suppressive effects of paraoxon on AHP. Our findings support the possible involvement of cAMP formation in the paraoxon induced AHP suppression and neuronal hyperexcitability, although activation of cAMP pathway may attenuates some effects of paraoxon. PMID- 17720248 TI - Mechanism of the CO-sensing heme protein CooA: new insights from the truncated heme domain and UVRR spectroscopy. AB - The bacterial CO-sensing heme protein CooA activates expression of genes whose products perform CO-metabolism by binding its target DNA in response to CO binding. The required conformational change has been proposed to result from CO induced displacement of the heme and of the adjacent C-helix, which connects the sensory and DNA-binding domains. Support for this proposal comes from UV Resonance Raman (UVRR) spectroscopy, which reveals a more hydrophobic environment for the C-helix residue Trp110 when CO binds. In addition, we find a tyrosine UVRR response, which is attributable to weakening of a Tyr55-Glu83 H-bond that anchors the proximal side of the heme. Both Trp and Tyr responses are augmented in the heme domain when the DNA-binding domain has been removed, apparently reflecting loss of the inter-domain restraint. This augmentation is abolished by a Glu83Gln substitution, which weakens the anchoring H-bond. The CO recombination rate following photolysis of the CO adduct is similar for truncated and full length protein, though truncation does increase the rate of CO association in the absence of photolysis; together these data indicate that truncation causes a faster dissociation of the endogenous Pro2 ligand. These findings are discussed in the light of structural evidence that the N-terminal tail, once released from the heme, selects the proper orientation of the DNA-binding domain, via docking interactions. PMID- 17720250 TI - Complexation of 5-fluorosalicylic acid with copper(II): a pH-potentiometric, UV vis spectroscopic, and electron spin resonance study by the two-dimensional simulation of spectra. AB - The copper(II)-5-fluorosalicylic acid system was investigated in water and 50 v/v% water-methanol mixture by pH potentiometry combined with UV-vis spectrophotometry, and by the two-dimensional ESR simulation method, respectively. The data revealed that the stable paramagnetic mono- and bis(salicylato) copper(II) complexes [CuLH(-1)] and [CuL2H(-2)](2-) are formed, and at low excess of ligand, the ESR-silent mixed hydroxo complex [Cu2L2H(-3)](-) is also a major species. By the two-dimensional ESR simulation method, the species [CuL]+ in the acidic region, and the minor dimer [Cu2L2H(-2)] were also identified, and the cis and trans isomers of [CuL2H(-2)](2-) were characterized. In frozen solutions, the ESR analysis revealed a slight rhombic distortion of coordination polyhedra for the latter three species. PMID- 17720249 TI - Sulfur K-edge XAS of WVO vs. MoVO bis(dithiolene) complexes: contributions of relativistic effects to electronic structure and reactivity of tungsten enzymes. AB - Molybdenum- or tungsten-containing enzymes catalyze oxygen atom transfer reactions involved in carbon, sulfur, or nitrogen metabolism. It has been observed that reduction potentials and oxygen atom transfer rates are different for W relative to Mo enzymes and the isostructural Mo/W complexes. Sulfur K-edge X-ray absorption spectroscopy (XAS) and density functional theory (DFT) calculations on [Mo(V)O(bdt)(2)](-) and [W(V)O(bdt)(2)](-), where bdt=benzene-1,2 dithiolate(2-), have been used to determine that the energies of the half-filled redox-active orbital, and thus the reduction potentials and MO bond strengths, are different for these complexes due to relativistic effects in the W sites. PMID- 17720251 TI - Morbidity and mortality of pneumococcal meningitis and serotypes of causative strains prior to introduction of the 7-valent conjugant pneumococcal vaccine in England. AB - OBJECTIVES: To assess the incidence of pneumococcal meningitis, associated deaths and serotypes of causative pneumococci in England prior to the inclusion of the 7 valent conjugated pneumococcal vaccine in the routine childhood immunisation programme in 2006. METHODS: Cases were identified using hospital episode statistics (HES) and voluntary reports or submission of isolates to the Health Protection Agency. Mortality data and population estimates were from the Office for National Statistics. RESULTS: Based on HES, the annual incidence of pneumococcal meningitis was about 1 case per 100,000 population between 1998 and 2005 (an average of approximately 480 cases per year) with case fatality rates increasing from 5% in <15 year olds to 30% in >64 year olds. Enhanced surveillance comprising a combination of voluntary reporting of cases and referral of isolates gave case ascertainment rates of 50-70% compared to those derived from HES, and similar case fatality rates. The age distribution of pneumococcal meningitis was similar with both datasets, infection being reported mostly commonly in children aged less than 5 years, with the highest incidence in children aged 2-11 months. Based on the serotype distribution of isolates obtained in 2005, the serotype coverage afforded by the 7-valent conjugate vaccine is 72% for patients aged less than 2 years. CONCLUSIONS: These data provide baseline information on the incidence of pneumococcal meningitis and associated mortality, together with the serotypes of infecting strains of pneumococci, which will be critical for evaluation of the public health impact of the 7-valent conjugated pneumococcal vaccine in England. PMID- 17720252 TI - Impact of protein acetylation in inflammatory lung diseases. AB - Chronic inflammatory lung diseases are characterized by increased expression of multiple inflammatory genes following activation by proinflammatory transcription factors, such as nuclear factor kappaB (NF-kappaB) and AP-1. Gene expression is, at least in part, regulated by acetylation of core histones through the action of coactivators, such as CREB-binding protein (CBP), which have intrinsic histone acetyltransferase (HAT) activity. Conversely gene repression is mediated via a combination of histone deacetylases (HDAC) and other corepressors. In asthma, the level of HAT activity is elevated in bronchial biopsies, whereas HDAC activity levels are only partially reduced and inhaled corticosteroids are able to reduce the increased HAT activity back to those seen in normal subjects. In contrast, in chronic obstructive pulmonary disease (COPD), there is a greater reduction in HDAC activity and HDAC2 expression but no difference in HAT activity. HAT and HDAC are also reported to modify a large and expanding number of nonhistone proteins, including nuclear import proteins, chaperones, cytoskeletal proteins, and other transcriptional factors, such as NF-kappaB and signal transducer and activation of transcription (STAT). Acetylation regulates several aspects of protein function and stability leading to differing effects on inflammatory gene expression and cell recruitment involved in the pathogenesis of inflammatory diseases. This review will examine the impact of acetylation on the function of key proteins involved in airway inflammatory disease and the effects of current therapies on acetylation status of key proteins. Further appreciation of the role of these changes may lead to the development of novel therapeutic approaches to inflammatory lung diseases that are currently difficult to treat. PMID- 17720253 TI - Depression in old age (75+), the PIKO study. AB - BACKGROUND: Old people (75+) are underrepresented in studies on the prevalence of and risk factors for depression while the number of elderly people suffering from this mood disorder may be considerably higher than previously assumed. The role- if any--of age and gender in 'Geriatric Depression' is still unclear. METHODS: In this community-based study, prevalence of depressive symptomatology and risk indicators were assessed in 2850 participants aged 75 years or more. A clinically relevant level of depressive symptoms was defined as a score of > or =16 on the Centre for Epidemiologic Studies Depression scale (CES-D). Demographic data and questions related to physical and psychological health were recorded. Simple and multiple logistic regression techniques were used to determine the risk indicators (Odds Ratios, OR, with 95% confidence intervals, CI) with apparent importance to this population. RESULTS: The prevalence of depressive symptoms was assessed to be 31.1%. This is considerably higher than what has been found in younger elderly samples. The bivariate age effect was OR 1.05 (95% CI=1.03 to 1.07). Controlling for confounding, the effect of gender and age on depressive symptoms disappeared. CONCLUSIONS: Depressive symptoms are highly prevalent in the elderly population and increase with age. This increase seems to be attributable to age-related changes in risk factors rather than to ageing itself. With regard to the risk factors found, attention should perhaps be paid to functional disability, loneliness and apprehensiveness for falling since these risk indicators are amenable for improvement. PMID- 17720254 TI - Monocyte and dendritic cell recruitment and activation during oral Salmonella infection. AB - Immunity to bacterial infection involves the joint effort of the innate and adaptive immune systems. The innate immune response is triggered when the body senses bacterial components, such as lipopolysaccharide, that alarm the body of the invader. An array of cell types function in the innate response. These cells are rapidly recruited to the infection site and activated to optimally perform their functions. The adaptive immune response follows the innate response, and one cell type in particular, dendritic cells (DCs), are the critical link between the innate and adaptive responses. This review will summarize recent data concerning the events that occur early during oral infection with the intracellular pathogen Salmonella, with emphasis on the phagocytic cells involved in combating the infection in the gut-associated lymphoid tissues. In particular, recent findings concerning the recruitment and activation of mononuclear phagocyte populations and dendritic cell subsets will be presented after an overview of the Salmonella infection model. PMID- 17720255 TI - The melody of crying. AB - As the speech of a normal hearing and a deaf person are different, author expects differences between the crying sound of normal hearing and hard-of-hearing infants as well. In this study the author determined by computerized algorithms the melody of 2762 crying sounds from 316 infants, and compared the results between infants with hearing disorders and normal hearing. The analysis of the crying sounds is aimed to work out a new, cheaper hearing screening method, which would give a new potential to the early detection of hearing disorders. All the applied steps were developed by automatic, computer-executed methods providing reproducible, objective results in contradistinction to some previous studies, which had applied manual methods and reached subjective results. Several possible ways for digital signal processing of the infant cry are discussed. A novel melody shape classification system was created to obtain a more precise distribution of the melodies by their shapes. The system determined 77 different categories, where the first 20 categories covered the 95% of the melodies. The applied methods were created and tested in a huge number of melodies. PMID- 17720256 TI - Is topical local anaesthesia necessary when performing paediatric flexible nasendoscopy? A double-blind randomized controlled trial. AB - OBJECTIVE: To evaluate the effectiveness of lignocain 2% and oxymetazoline 0.025% compared to oxymetazoline 0.025% alone when administered prior to fibreoptic nasendoscopy in paediatric patients. STUDY DESIGN: Prospective, randomized controlled, double-blind study. A group of 56 children, undergoing nasendoscopy to determine adenoidal size, were randomized into two groups and received either lignocain 2% and oxymetazoline 0.025% or oxymetazoline 0.025% alone prior to fibreoptic nasendoscopy. SETTING: A tertiary care Paediatric Hospital. METHOD: The endoscopist recorded the ease of performance of the procedure, cooperation of patient and quality of the view achieved using a visual analogue scale (VAS). The pain and anxiety levels of the child were recorded before, during and immediately after the procedure, using a VAS. The duration of performing the procedure was recorded from insertion of the endoscope into the nostril until removal. RESULTS: All 56 children were able to undergo the endoscopy and the full anxiety and pain assessment was done. Three children were excluded because they have undergone nasendoscopies before. Of the 53 patients included, 27 children received solution A (oxymetazoline 0.025%) and 26 children received solution B (oxymetazoline 0.025% and lignocain 2%). There was no statistical difference between the two groups regarding the duration of the endoscopy, quality of view, ease of performance and cooperation of the patients. The median pain and anxiety scores were not significantly different between the two groups. CONCLUSIONS: This study concludes that the use of a decongestant (oxymetazoline) for paediatric nasendoscopy is just as effective as the use of oxymetazoline with lignocain. Pain and anxiety is not increased in the absence of lignocain. PMID- 17720258 TI - Life-history responses of Daphnia magna Straus to binary mixtures of toxic substances: pharmacological versus ecotoxicological modes of action. AB - Two prevailing theoretical models: concentration addition (CA) and independent action (IA), predict mixture toxicity on the basis of known toxicities of the mixture components. To date, both models have been in most occasions evaluated using unicellular in vivo responses or biochemical in vitro responses. However, when considering more complex models such as the whole organism physiology or life-history traits, the dominant ecotoxicological mode of action, based on the exposure concentrations at which various toxicological effects become operative at the level of whole organism, should be considered. Offspring production in Daphnia magna is driven by the resources acquired from food, and the number of live offspring produced by an organism is the result of two independent factors: the number of eggs produced and the percentage of eggs that survive egg development. In this study joint toxicity effects on offspring production in D. magna were tested using binary mixtures of toxic contaminants known to specifically impair food acquisition (lambda-cyhalothrin and cadmium) or to cause egg mortality during development (3,4 dichloroaniline). Tests were performed using a simplified 10-day reproduction assay initiated with gravid females. The results obtained indicate that irrespective of their primary pharmacological mode of action, the joint toxicity of cadmium and lambda-cyhalothrin was predicted by the CA model, whereas the joint toxicity of cadmium and 3,4 dichloroaniline was predicted by the IA model. Thus, the results obtained indicate that for life history traits such as reproduction responses, the dominant ecotoxicological rather than the pharmacological mode of action should be used for predicting joint mixture effects. PMID- 17720257 TI - Repeated amphetamine administration outside the home cage enhances drug-induced Fos expression in rat nucleus accumbens. AB - Induction of the immediate early gene protein product Fos has been used extensively to assess neural activation in the striatum after repeated amphetamine administration to rats in their home cages. However, this technique has not been used to examine striatal activation after repeated administration outside the home cage, an environment where repeated drug administration produces more robust psychomotor sensitization. We determined the dose-response relationship for amphetamine-induced psychomotor activity and Fos expression in nucleus accumbens and caudate-putamen 1 week after repeated administration of amphetamine or saline in locomotor activity chambers. Repeated administration of amphetamine enhanced amphetamine-induced locomotor activity and stereotypy and Fos expression in nucleus accumbens, but not in caudate-putamen. In comparison, levels of Fos expression induced by 1mg/kg amphetamine were not altered in nucleus accumbens or caudate-putamen by repeated amphetamine administration in the home cage. Double-labeling of Fos protein and enkephalin mRNA indicates that Fos is expressed in approximately equal numbers of enkephalin-negative and enkephalin-positive neurons in nucleus accumbens and caudate-putamen following injections outside the home cage. Furthermore, repeated amphetamine administration increased drug-induced Fos expression in enkephalin-positive, but not enkephalin-negative, neurons in nucleus accumbens. We conclude that repeated amphetamine administration outside the home cage recruits the activation of enkephalin-containing nucleus accumbens neurons during sensitized amphetamine induced psychomotor activity. PMID- 17720259 TI - The autonomic nervous system regulates gastric ghrelin secretion in rats. AB - Plasma ghrelin levels are responsive to short- and long-term nutrient fluctuation, but the mechanisms of its regulation are largely unknown. To explore the role of the autonomic nervous system in the regulation of ghrelin secretion, we measured plasma ghrelin levels after administration of cholinergic and adrenergic agents in rats under normally fed and 48-h fasting conditions. To assess the short- and long-term effects of vagotomy on ghrelin secretion, plasma ghrelin levels and stomach ghrelin levels and gene expressions were measured in rats subjected to fed or fasting. Additionally, we investigated whether plasma ghrelin levels were affected by the anorexigenic gastrointestinal peptides cholecystokinin and somatostatin. In the pharmacological study, plasma ghrelin levels were increased by a muscarinic agonist, an alpha-adrenergic antagonist, and a beta-adrenergic agonist, and decreased by a muscarinic antagonist and an alpha-adrenergic agonist. Vagotomy inhibited ghrelin secretion acutely, but promoted ghrelin release from the stomach at later time points. Stomach ghrelin mRNA levels were unchanged after fasting, but were significantly upregulated in vagotomized rats. The change of plasma ghrelin levels in nutrient fluctuation was independent of the endogenous effects of cholecystokinin and somatostatin. This study demonstrates that stomach ghrelin secretion is modulated by both the cholinergic and adrenergic arms of the autonomic nervous system. The dissociation between the short- and long-term effects of vagotomy on plasma ghrelin level indicates that an additional neural control mechanism might be involved in the regulation of ghrelin secretion. PMID- 17720261 TI - Pseudo Wellens T-waves in patients with suspected myocardial infarction: how cardiac magnetic resonance imaging can help the diagnosis. AB - Wellens' syndrome is characterized by symmetrically inverted T-waves in the precordial leads suggestive of impending myocardial infarction due to a critical proximal left anterior descending (LAD) stenosis. We describe three unusual cases of patients with such electrocardiographic abnormality in which coronary angiography ruled out the presence of critical coronary stenosis and cardiac magnetic resonance imaging excluded the presence of acute or chronic myocardial infarction. PMID- 17720262 TI - Acute effects of smoking on coronary flow velocity reserve and ventricular diastolic functions. AB - Although it is well known that chronic effect of smoking on cardiovascular system, relation between coronary vascular reactivity and ventricular functions after acute smoking has not been well understood. The purpose of this study was to assess the relation between coronary flow velocity reserve and ventricular diastolic functions measured by tissue Doppler imaging after acute smoking. We found that coronary flow velocity and diastolic functions of right ventricle were decreased. Also, there was a correlation between coronary flow velocity reserve and diastolic ratio of the ventricle. Acute smoking may affect diastolic functions of the ventricles, especially right ventricle via changes of coronary flow. PMID- 17720260 TI - Three autocrine feedback loops determine HIF1 alpha expression in chronic hypoxia. AB - Hypoxia occurs in cancer, prolonged exercise, and long-term ischemia with durations of several hours or more, and the hypoxia-inducible factor 1 (HIF1) pathway response to these conditions differs from responses to transient hypoxia. We used computational modeling, validated by experiments, to gain a quantitative, temporal understanding of the mechanisms driving HIF1 response. To test the hypothesis that HIF1 alpha protein levels during chronic hypoxia are tightly regulated by a series of molecular feedbacks, we took into account protein synthesis and product inhibition, and analyzed HIF1 system changes in response to hypoxic exposures beyond 3 to 4 h. We show how three autocrine feedback loops together regulate HIF 1 alpha hydroxylation in different microenvironments. Results demonstrate that prolyl hydroxylase, succinate and HIF1 alpha feedback determine intracellular HIF1 alpha levels over the course of hours to days. The model provides quantitative insight critical for characterizing molecular mechanisms underlying a cell's response to long-term hypoxia. PMID- 17720264 TI - Auricall. A new device for a non-invasive, wireless, continuous monitoring of oxygen saturation and heart rate in patients with heart failure. AB - Sleep apnoea syndrome is frequent in patients with heart failure and associated with a worse prognosis. We evaluated a new device (Auricall) for non-invasive, continuous recording of oxygen saturation (SpO(2)) and heart rate (HR) in patients with heart failure. We studied 20 patients (mean age 48.43+/-14.4 years, NYHA class II-III). All patients were requested to carry the device for at least 36 h and to write a diary during the recording time. Satisfactory recording of SpO(2) and HR was possible to obtain in 18 of 20 patients. Indeed 9 out of 18 patients showed significant periodic changes in SpO(2) during sleep. Therefore, Auricall is a useful tool to non-invasively monitor SpO(2) and HR in patients with heart failure and to detect breathing disorders in these patients. PMID- 17720265 TI - Benefits of in-situ synthesized microarrays for analysis of gene expression in understudied microorganisms. AB - Although the genome sequences of many microorganisms are now known, whole-genome DNA microarray platforms consisting of PCR amplicon, or oligonucleotide elements printed onto glass slides have been readily available for only a relatively few, highly studied microorganisms. For those microorganisms more recently cultured or studied by fewer investigators it has been difficult to justify the initial time and expense of developing such array platforms especially if only a limited number of gene expression studies are envisioned. However, in-situ synthesized oligonucleotide (ISO) arrays can be inexpensively fabricated on an 'as needed' basis with a reduced initial investment in time, personnel, resources, and costs. To evaluate the performance of one ISO array platform, gene expression patterns in Geobacter sulfurreducens under nitrogen-fixing conditions were compared with results from quantitative reverse transcriptase PCR (qRT-PCR) and previously published data from a similar experiment using spotted PCR amplicon arrays. There were strong correlations between the results of the ISO arrays and the results from qRT-PCR (r(2)=0.762) and spotted array (r(2)=0.744) analyses. After initial use the ISO arrays could be successfully stripped and reused. The increased flexibility in array design and reusability coupled with a lower initial investment in terms of fabrication time and cost for the ISO arrays suggest that they may be the preferred approach when investigating gene expression in microorganisms, especially when only a few expression studies are required. PMID- 17720266 TI - A feasibility study of image-guided hypofractionated conformal arc therapy for inoperable patients with localized non-small cell lung cancer. AB - We treated 36 cases of stage I/II non-small cell lung cancer in inoperable patients. Treatments were planned to a total isocenter dose of 60Gy (8x7.5Gy) based on a dynamic field shaping arc, employing one arc to span as much area as possible and if needed additional weighted segments. The 2 year infield progression free probability is 65%. Disease-specific survival is 75% at 2 years. No patients experienced grade 3-4 toxicity. PMID- 17720267 TI - Prefrontal activity during koh-do incense discrimination. AB - Whenever we make reasoned decisions we must refer to relevant knowledge obtained through past experience. Our brains test multiple premises and select whichever conclusion serves as the best explanation of the current conditions. In the present study we examined the prefrontal activity of koh-do experts with near infrared spectroscopy while they reasoned about odours during an incense discrimination task. These practitioners of the Japanese incense ceremony have been trained to form and manipulate abstract images of complex olfactory stimuli represented in a multidimensional symbolic space in the mind. In koh-do experts, the right PFC showed a consistent stimulus-non-selective response during discrimination and the left PFC showed phasic stimulus-selective responses modulated by the internal subjective state of the reasoning process. These two dissociated functions appeared to cooperate with each other during reasoning. In contrast, koh-do beginners did not show the organized response pattern found in experts. The results suggest that both PFCs contribute to abductive reasoning, but do so differently through different stages of the process. PMID- 17720268 TI - LDL receptor deficiency results in decreased cell proliferation and presynaptic bouton density in the murine hippocampus. AB - An aberrant cholesterol metabolism in the brain may contribute to the pathogenesis of Alzheimer's disease (AD). The LDL receptor (LDLR) regulates plasma cholesterol levels and recently we and others obtained evidence that it is also involved in regulating brain cholesterol homeostasis. Moreover, we found that LDLR-deficient mice display impaired spatial memory. Because cholesterol, in part derived from cellular uptake via LDLR, is required for peripheral cell proliferation and growth, we examined the effect of absence of the LDLR on hippocampal proliferation and the density of synaptic connections. Mice deficient for the LDLR displayed a reduced number of proliferating (BrdU-labeled) cells in the hippocampus as compared to wild type control mice. In addition, the number of synaptophysin-immunoreactive presynaptic boutons in the hippocampal CA1 and the dentate gyrus (DG) areas, but not in cortical areas, was lower in the LDLR knockout mice than in the control mice. In vitro experiments showed that LDLR activity is increased when cell growth is enhanced by the addition of N2 supplement. This further supports a role for the LDLR in the outgrowth of neurites. These findings support the notion that, similar to its role in the periphery, the LDLR is important for the cellular uptake of cholesterol in the brain and that disturbance of this process affects neuronal plasticity. PMID- 17720269 TI - The relationship between retrieval success and task performance during the recognition of meaningless shapes: an event-related near-infrared spectroscopy study. AB - Retrieval success of episodic memory has been studied intensively through the investigation of old/new effects. Recognized stimuli used in event-related functional magnetic resonance imaging studies on old/new effects have been words and visual materials which can evoke semantic associations. To elucidate the neural basis of retrieval success uninfluenced by semantic processing, we investigated the correlation between old/new effects and task performance during the recognition of meaningless shapes, by using event-related near-infrared spectroscopy. Forty-two right-handed subjects made recognition judgments about old (studied) or new (unstudied) meaningless shapes. The old/new effects of the shapes were positively correlated with task performance in the bilateral inferior lateral parietal cortex (ILP), but predominantly in the left ILP. This finding indicated that the ILP was directly associated with retrieval success and its lateralization was consistently left-sided irrespective of the type of stimulus. PMID- 17720270 TI - Membrane properties of rat medial vestibular nucleus neurons in vivo. AB - In our previous study using the whole-cell patch clamp technique combined with reverse transcription-polymerase chain reaction analysis in rat brainstem slices, we demonstrated that the classification of neurons in the medial vestibular nucleus (MVN) based on three membrane properties detected as voltage response properties to depolarizing and hyperpolarizing current pulses, namely afterhyperpolarization (AHP) profiles, firing patterns, and response patterns to hyperpolarizing current pulses, is useful for clarifying the relationship between membrane properties and cellular markers for excitatory and inhibitory neurons. These membrane properties characterized in vitro, however, have not been ascertained in vivo. To address this issue, we applied the whole-cell patch clamp recording method to in vivo preparations of young adult rats and investigated voltage responses to depolarizing and hyperpolarizing current pulses. We found three AHP profiles, three firing patterns, and three response patterns to hyperpolarizing current pulses in MVN neurons in vivo that were characterized in our previous in vitro study. The MVN neuronal populations classified on the basis of the three membrane properties in vivo were comparable to those obtained in vitro. This finding indicates that the classification of MVN neurons based on the three membrane properties is applicable to in vivo preparations. PMID- 17720271 TI - Genetic factors affecting sexual reproduction in toxigenic Fusarium species. AB - Mycotoxin producing capability greatly varies within species. In theory, the major source of this variability is meiotic recombination. However, a number of important toxigenic species have no known sexual stage and, therefore, the origin of the intraspecific diversity in these fungi is poorly understood. Mating in sexually reproducing Ascomycetes is controlled by MAT genes, but fungi with no known sexual stage also may have fully functional, constitutively transcribed mating type genes. The MAT genes, MAT1-1-1 and MAT1-2-1 encode putative transcription factors which, besides regulating pheromone and pheromone receptor genes, may affect other genes not involved directly in the mating process. By comparing the transcript profiles of a DeltaMAT1-2-1 knock-out mutant and the wild type of Fusarium verticillioides, more than 200 ESTs, either down- or up regulated in the mutant, were identified. Sequences encoding proteins involved in protein synthesis and metabolism occurred more frequently among ESTs up-regulated in the mutant, while sequences involved in cell signaling and communication were more frequent in the down-regulated subset of ESTs. The lack of fertility in fungi with no known sexual stage and the limited fertility of local populations of sexually reproducing fungi are probably due to changes in one or more of numerous genes that cause female sterility. A number of gene disruption mutants of Fusarium proliferatum were assessed for their mating capabilities. Fphch (a Het-C homologue), Fpmtr (an amino acid transporter gene), and Fpnitr1 (a putative nitrilase encoding gene) encode proteins in seemingly unrelated pathways, but mutations at any of these loci can reduce female fertility. Thus, a number of genes, with functions not related directly to mating, can influence the frequency of sexual reproduction indicating that this process requires the concerted operation of many factors not obviously connected to female fertility/sterility. PMID- 17720272 TI - Protein expression from synthetic genes: selection of clones using GFP. AB - Construction of synthetic genes is today the most elegant way to optimize the heterologous expression of a recombinant protein. However, the selection of positive clones that incorporate the correct synthetic DNA fragments is a bottleneck as current methods of gene synthesis introduce 3.5 nucleotide deletions per kb. Furthermore, even when all predictable optimizations for protein production have been introduced into the synthetic gene, production of the protein is often disappointing: protein is produced in too low amounts or end up in inclusion bodies. We propose a strategy to overcome these two problems simultaneously by cloning the synthetic gene upstream of a reporter gene. This permits the selection of clones devoid of frame-shift mutations. In addition, beside nucleotide deletion, an average of three non-neutral mutations per kb are introduced during gene synthesis. Using a reporter protein downstream of the synthetic gene, allows the selection of clones with random mutations improving the expression or the folding of the protein of interest. The problem of errors found in synthetic genes is then turned into an advantage since it provides polymorphism useful for molecular evolution. The use of synthetic genes appears as an alternative to the error-prone PCR strategy to generate the variations necessary in protein engineering experiments. PMID- 17720273 TI - Weight gain in type 2 diabetes mellitus--not all uphill. AB - OBJECTIVE: The goal of this study, of type 2 diabetes mellitus patients, treated in a referral community setting, was to follow the history of weight changes, in relation to the changing treatment modalities, and to detect independent risk factor and predictors for weight gain. RESEARCH METHODS: 366 outpatients with type 2 diabetes (T2DM) were followed longitudinally for at least 5 years. 310 patients were treated with oral hypoglycemic agents and 56 patients had insulin treatment added to the oral therapy. RESULTS: The two groups did no differ significantly in the duration of diabetes, age of onset and admission HbA1c. The mean weight at admission was 78.9+/-15.1 and 76.7+/-15.0 kg (ns) respectively. No significant weight changes were noted on initiation of oral treatment and at final visit. The commencing of insulin therapy was the only step associated with a significant 3.7 kg increase in body weight (p<0.001) with a significant reduction in HbA1c (-1.4%, p<0.001). These changes however, followed a decrease in body weight that preceded insulin therapy. Mean weight at follow-up did not exceed the self-reported weight prior to the diagnosis of diabetes. DISCUSSION: The results show that weight gain does not necessarily accompany treatment of T2DM. Insulin therapy in T2DM is associated with some weight gain, mostly due to correction of glycemia and improvement of weight loss prior to insulin treatment. This should encourage the timely addition and combining of appropriate therapeutic modalities in order to achieve good glycemic control. PMID- 17720274 TI - Prevalence of celiac disease in type 1 diabetes mellitus in North West Rajasthan, India. PMID- 17720275 TI - Evaluation systems for anti-HCV drugs. AB - Development of therapeutics for chronic hepatitis C has been hampered by the lack of an efficient cell culture system and a small animal model for the hepatitis C virus (HCV). An RNA replicon system, in which the HCV genome replicates autonomously in cells, and replication competent viruses derived from an HCV genotype 2a JFH1 strain efficiently propagating in Huh7 cells have been developed, and these systems have contributed to the evaluation of anti-HCV drugs targeted to viral and host proteins involved in the replication of HCV. Several compounds counteracting the viral enzymes, such as RNA polymerase and proteases, and host proteins involved in the lipid synthesis and protein folding are reported to have anti-HCV activities based on assessments using these in vitro systems. Furthermore, a mouse model transplanted with human liver fragments was shown to be capable of replicating HCV and has been used to evaluate the efficacy of antiviral drugs in vivo. In this review, we summarize information regarding systems for studying the HCV life cycle and potential new targets for therapeutic intervention for chronic hepatitis C. PMID- 17720276 TI - Efficacy and side effects of cisplatin- and carboplatin-based doublet chemotherapeutic regimens versus non-platinum-based doublet chemotherapeutic regimens as first line treatment of metastatic non-small cell lung carcinoma: a systematic review of randomized controlled trials. AB - Evidence suggests that platinum-based regimens confer a better survival in patients with non-small cell lung carcinoma (NSCLC). However, evidence is lacking regarding the specific effects of cisplatin or carboplatin when compared to non platinum-based doublets. METHODS: Meta-analysis of all randomized trials comparing non-platinum-based with platinum-based doublet regimens given as first line treatment for NSCLC. Relative risks were calculated for all outcomes ascertained. Sensitivity analysis, using methodological quality of the trials and different measures of effect, was undertaken. RESULTS: Seventeen trials, comprising 4920 patients were included. The use of platinum-based doublet regimens was associated with a slightly higher survival at 1 year (RR=1.08, 95% CI 1.01-1.16, p=0.03), better partial response (RR=1.11, 95% CI 1.02-1.21, p=0.02), with a higher risk of anemia, nausea, and neurotoxicity. Cisplatin-based doublet regimens improved survival at 1 year (RR=1.16, 95% CI 1.06-1.27, p=0.001), complete response (RR=2.29, 95% CI 1.08-4.88, p=0.03), partial response (RR=1.19, 95% CI 1.07-1.32, p=0.002) with an increased risk of anemia, neutropenia, neurotoxicity and nausea. Conversely, carboplatin-based doublet regimens did not increase survival rate at 1 year (RR=0.95, 95% CI 0.85-1.07, p=0.43). There was a statistically significant difference between the effect of cisplatin compared to carboplatin (p=0.05). Carboplatin-based doublet regimen included a higher risk of anemia and thrombocytopenia, but no increased nausea and/or vomiting, contrarily to cisplatin. Sensitivity analyses showed that the results were robust to the exclusion of lesser quality trials and the choice of the measure of effect. CONCLUSION: We provide additional evidence that cisplatin, but not carboplatin-based doublet regimens are associated with a slightly better survival compared to non-platinum-based doublet regimens. Side effects of cisplatin- and carboplatin-based regimens differ between each other and when compared to non-platinum doublets. Although this analysis has limitations, it may provide valuable information to clinicians when choosing the appropriate regimen for patients with non-small cell lung cancer. PMID- 17720277 TI - Short wait times for patients seeking cosmetic botulinum toxin appointments with dermatologists. AB - BACKGROUND: Wait times for both routine and urgent dermatology appointments typically exceed 3 to 4 weeks. Many factors affecting physician workforce adequacy and patient access have been explored, but little is known about the impact of increasing numbers of doctors offering cosmetic services. OBJECTIVE: We sought to evaluate access to dermatologists for patients requesting cosmetic services. METHODS: Scripted patient telephone calls were made to 898 dermatologists in 12 metropolitan areas to assess wait times for an appointment to receive cosmetic botulinum toxin injections. The areas chosen were surveyed completely, and respondents represented about one tenth of practicing dermatologists in the United States. The methodology was identical to that used in a previous study of wait times for evaluation of a changing mole (a possible indicator of malignancy). RESULTS: Half of dermatologist respondents (455, 50.7%) offered appointments for botulinum toxin injections, and the median wait time was 8 days. Acceptance rates and wait times varied greatly by geographic area (range of median wait times 6.0-32.5 days), with dermatologists in Miami, Fla, and Orange County, California, most likely to provide a botulinum toxin appointment with a short wait time. Many dermatologists (241, 27%) employed physician extenders, and 39% of these extenders also offered appointments for botulinum toxin injections (median wait time 6 days). In comparison with a previous study showing median wait times of 26 days for evaluation of a changing mole in these communities, wait times for cosmetic injections were significantly shorter (P < .001). LIMITATIONS: The metropolitan areas surveyed contain no highly rural areas and do not represent a random sample of all US dermatology practice sites. The cosmetic and medical studies were not conducted concurrently, but were carried out in the same metropolitan areas. CONCLUSIONS: Patients seeking a cosmetic botulinum toxin injection have more rapid access to dermatologists than has been previously reported for patients seeking urgent consultation for a changing mole. This study cannot differentiate between many possible explanations for the observed differences in wait times. Because physicians in many other specialties with physician shortages are also offering cosmetic services, further studies are needed to assess the broader policy implications of these findings. PMID- 17720278 TI - When is a defibrillator not a defibrillator? When it's like a clock radio.... The challenge of usability and patient safety in the real world. PMID- 17720279 TI - Identification and characterization of an insulin receptor substrate 4 interacting protein in rat brain: implications for longevity. AB - The hypothalamus is organized as a collection of distinct, autonomously active nuclei that regulate discrete functions, such as feeding activity and metabolism. We used suppression subtractive hybridization (SSH) to identify genes that are enriched in the hypothalamus of the rat brain. We screened a subtractive library of 160 clones, and 4 genes that were predominantly expressed in the hypothalamus, compared to other brain regions. The mRNA for a member of the WD-repeat family of proteins, WDR6, was abundantly expressed in the hypothalamus, and we found that WDR6 interacted with insulin receptor substrate 4 (IRS-4) in the rat brain. Interestingly, WDR6 gene expression in the hypothalamic arcuate nucleus was decreased by caloric restriction, and in growth hormone (GH)-antisense transgenic rats, both of which are associated with an increased life span. Insulin-like growth factor (IGF)-I and insulin treatment increased WDR6 gene expression in mouse hypothalamus-derived GT1-7 cells. Our results might suggest that WDR6 participates in insulin/IGF-I signaling and the regulation of feeding behavior and longevity in the brain. PMID- 17720280 TI - Case control analysis of LRRK2 Gly2385Arg in Alzheimer's disease. AB - Alzheimer's disease (AD) pathology has been described in Parkinson's disease (PD) patients with leucine-rich repeat kinase-2 (LRRK2) mutations. A common LRRK2 Gly2385Arg variant has been widely shown to be associated with a twofold increased risk of PD in various Asian populations. In a case control study, the frequency of the heterozygous Gly2385Arg genotype was demonstrated in 4.3% of AD compared to 4.5% in controls (odds ratio=0.94, 95% CI 0.37-2.42, p=1.0). The Gly2385Arg variant does not appear to modulate the risk of AD in our population. PMID- 17720281 TI - Mitochondrial dysfunction precedes neurodegeneration in mahogunin (Mgrn1) mutant mice. AB - Oxidative stress, ubiquitination defects and mitochondrial dysfunction are commonly associated with neurodegeneration. Mice lacking mahogunin ring finger-1 (MGRN1) or attractin (ATRN) develop age-dependent spongiform neurodegeneration through an unknown mechanism. It has been suggested that they act in a common pathway. As MGRN1 is an E3 ubiquitin ligase, proteomic analysis of Mgrn1 mutant and control brains was performed to explore the hypothesis that loss of MGRN1 causes neurodegeneration via accumulation of its substrates. Many mitochondrial proteins were reduced in Mgrn1 mutants. Subsequent assays confirmed significantly reduced mitochondrial complex IV expression and activity as well as increased oxidative stress in mutant brains. Mitochondrial dysfunction was obvious many months before onset of vacuolation, implicating this as a causative factor. Compatible with the hypothesis that ATRN and MGRN1 act in the same pathway, mitochondrial dysfunction and increased oxidative stress were also observed in the brains of Atrn mutants. Our results suggest that the study of Mgrn1 and Atrn mutant mice will provide insight into a causative molecular mechanism common to many neurodegenerative disorders. PMID- 17720282 TI - Oxoisoaporphine alkaloid derivatives: synthesis, DNA binding affinity and cytotoxicity. AB - A series of novel oxoisoaporphine alkaloid derivatives, 9-aminoalkanamido-1 azabenzanthrone (general formula Ar-NHCO(CH(2))(n)NR(2), Ar=1-azabenzanthrone, n=1, 2 or 3), had been synthesized. Compared with 1-azabenzanthrone, the derivatives had significantly higher DNA binding affinity with calf thymus DNA, and higher potent cytotoxicity against different tumor cell lines. The cytotoxicity and the structure-activity relationship of the prepared compounds were studied. The derivatives with two methylene groups (n=2), and piperidine or ethanolamine functional group in the side chain exhibited highest DNA binding affinity and cytotoxicity. PMID- 17720284 TI - Investigations on indoor Radon in Austria, part 2: Geological classes as categorical external drift for spatial modelling of the Radon potential. AB - Geological classes are used to model the deterministic (drift or trend) component of the Radon potential (Friedmann's RP) in Austria. It is shown that the RP can be grouped according to geological classes, but also according to individual geological units belonging to the same class. Geological classes can thus serve as predictors for mean RP within the classes. Variability of the RP within classes or units is interpreted as the stochastic part of the regionalized variable RP; however, there does not seem to exist a smallest unit which would naturally divide the RP into a deterministic and a stochastic part. Rather, this depends on the scale of the geological maps used, down to which size of geological units is used for modelling the trend. In practice, there must be a sufficient number of data points (measurements) distributed as uniformly as possible within one unit to allow reasonable determination of the trend component. PMID- 17720283 TI - Gonococcal transferrin binding protein chimeras induce bactericidal and growth inhibitory antibodies in mice. AB - We have previously demonstrated the full-length gonococcal transferrin binding proteins (TbpA and TbpB) to be promising antigens in the development of a protective vaccine against Neisseria gonorrhoeae. In the current study we employed a genetic chimera approach fusing domains from TbpA and TbpB to the A2 domain of cholera toxin, which naturally binds in a non-covalent fashion to the B subunit of cholera toxin during assembly. For one construct, the N-terminal half of TbpB (NB) was fused to the A2 subunit of cholera toxin. In a second construct, the loop 2 region (L2) of TbpA was genetically fused between the NB domain and the A2 domain, generating a double chimera. Both chimeras were immunogenic and induced serum bactericidal and vaginal growth-inhibiting antibodies. This study highlights the potential of using protective epitopes instead of full-length proteins in the development of an efficacious gonococcal vaccine. PMID- 17720285 TI - Factors contributing to radiocaesium variability in upland sheep flocks in west Cumbria (United Kingdom). AB - Following the Chernobyl accident in 1986, restrictions were placed on the movement and slaughter of sheep within upland areas of the UK because radiocaesium activity concentrations in their meat exceeded 1000 Bq kg(-1) fresh weight. Some farms remain under restriction in 2007. From 1991 to 1993 detailed studies were conducted on three sheep farms within the restricted area of west Cumbria to systematically assess the various parameters which may contribute to the observed variability in radiocaesium activity concentrations within sheep flocks. This paper reports the spatial variation in soil and vegetation activity concentrations across the grazed areas at these farms and determines the influence of grazing behaviour on variability in (137)Cs activity concentrations between individual sheep within the flocks. Together with previously reported results, these new data are used to draw conclusions on the factors determining variability within the three flocks. However, the factors are too site specific to be able to generalise the findings to other farms within the restricted areas of the UK. PMID- 17720286 TI - Health risks of heavy metals in contaminated soils and food crops irrigated with wastewater in Beijing, China. AB - Consumption of food crops contaminated with heavy metals is a major food chain route for human exposure. We studied the health risks of heavy metals in contaminated food crops irrigated with wastewater. Results indicate that there is a substantial buildup of heavy metals in wastewater-irrigated soils, collected from Beijing, China. Heavy metal concentrations in plants grown in wastewater irrigated soils were significantly higher (Por=10 mg Ni/L resulted in delayed hatching at an age of 96 h, in decreased locomotory activity at an age of 5 days, and increased mortality at an age of 11 days (LC20=9.5 mg Ni/L). The observed LOEC for locomotory activity (7.5 mg Ni/L) is in the range of environmentally relevant concentrations. Since locomotory activity was already affected by acute exposure, this parameter is recommended to supplement commonly recorded endpoints of toxicity. PMID- 17720288 TI - School absenteeism and school refusal behavior in youth: a contemporary review. AB - Absenteeism from school is a serious public health issue for mental health professionals, physicians, and educators. The prevalence of unexcused absences from school exceeds that of major childhood behavior disorders and is a key risk factor for violence, injury, substance use, psychiatric disorders, and economic deprivation. This article involves a contemporary research review on absenteeism prevalence, comorbid physical and psychiatric conditions, classification, contextual risk factors, cross-cultural variables, assessment, intervention, and outcome. Contextual risk factors include homelessness and poverty, teenage pregnancy, school violence and victimization, school climate and connectedness, parental involvement, and family variables, among others. A description of intervention includes medical, clinical, and systemic interventions. Medical professionals, community- and school-based mental health professionals, and educators are encouraged to fully understand the parameters of school absenteeism to develop better, consensual policies regarding definition, classification, assessment, and intervention of youths with problematic school absenteeism. PMID- 17720289 TI - A critical examination of home care: end of life care as an illustrative case. AB - Drawing on end of life care as an illustrative case, this paper critically examines the provision of care in the home, identifying a number of inherent tensions. For 60 years the hospital has been the preferred site of care. However, the UK caring division of labour is currently undergoing a process of (re)domestication and the provision of home care is increasingly regarded as a 'gold standard' for the organisation of care, in institutional and domestic contexts. In this paper we argue that while 'home care' policies serve a range of professional and political agendas, they contain unacknowledged contradictions and strains, creating challenges for both family and professional carers. The realities of home care are examined through reconceptualising qualitative data generated from three research projects concerned with dying in the community. We argue that, whilst previous work has highlighted the burdens the redomestication of care places upon carers, home care philosophies and policies have led to over romanticised notions of care which privilege the value of caring relationships without acknowledging the dynamic interaction of such social relationships with the actual work of caring. Moreover, such policy trends have created a nexus of social expectations and obligations for which modern society is unprepared. With reference to both end of life care, and home care more widely, we argue that health care planners and professionals need to think more critically about the way care is delivered. Home is not merely about a physical space, but the social and emotional relationships therein. Good 'home care,' characterised by attention to patient-centred needs and flexible in design and scope, does not have to be located within the private sphere; relationships may actually be maintained and nurtured by enabling people to have a realistic choice of care in an institution. PMID- 17720290 TI - Perceptual biases in processing facial identity and emotion. AB - Normal observers demonstrate a bias to process the left sides of faces during perceptual judgments about identity or emotion. This effect suggests a right cerebral hemisphere processing bias. To test the role of the right hemisphere and the involvement of configural processing underlying this effect, young and older control observers and patients with right hemisphere damage completed two chimeric faces tasks (emotion judgment and face identity matching) with both upright and inverted faces. For control observers, the emotion judgment task elicited a strong left-sided perceptual bias that was reduced in young controls and eliminated in older controls by face inversion. Right hemisphere damage reversed the bias, suggesting the right hemisphere was dominant for this task, but that the left hemisphere could be flexibly recruited when right hemisphere mechanisms are not available or dominant. In contrast, face identity judgments were associated most clearly with a vertical bias favouring the uppermost stimuli that was eliminated by face inversion and right hemisphere lesions. The results suggest these tasks involve different neurocognitive mechanisms. The role of the right hemisphere and ventral cortical stream involvement with configural processes in face processing is discussed. PMID- 17720291 TI - Refractory psychotic symptoms in a patient with homozygous sickle cell disease: a 24-month follow-up. AB - The present report describes a case of a 33-year old male patient with homozygous sickle cell disease (SCD) with comorbid psychotic symptoms. The systematical evaluation revealed an intimate association between acute SCD complications, associated with hematological abnormalities, and psychotic symptoms worsening. Clozapine was effective in controlling psychotic symptoms refractory to previous antipsychotic trials. PMID- 17720292 TI - Elevated levels of MCP-1, MIP-alpha and MIP-1 beta in the bronchoalveolar lavage (BAL) fluid of patients with mustard gas-induced pulmonary fibrosis. AB - OBJECTIVE: Role of chemokines in the pathogenesis of pulmonary fibrosis (PF) due to sulfur mustard (SM) gas inhalation. PATIENTS: 18 veterans with SM gas-induced PF, 15 patients with IPF and 18 normal as controls. INTERVENTION: Chest roentgenograms, PFTs, the percentage DLCO, high-resolution CT scans of the chest, and analyses of BAL fluids for chemokines (MCP-1, MIP-1 alpha, and MIP-1 beta) were performed in all cases. RESULTS: There were significant differences in chemokines (MCP-1, MIP-1 alpha, and MIP-1 beta) levels of BAL fluid between patients with PF and healthy controls (p<0.0006). MCP-1 and MIP-1 alpha levels in BAL fluid correlate only with the percentage and the absolute number lymphocytes of the BAL fluid in patients with PF due to SM gas inhalation (p=0.0006/p=0.03; p=0.04/p=0.02; respectively). The BAL fluid level of MIP-alpha in SM gas-induced PF was significantly correlated with the number of lymphocytes (r=-0.56, p=0.01), neutrophils (r=-0.50, p=0.03) and eosinophils (r=-0.49, p=0.03). A significant negative correlation was observed between the percentage of Dlco and MCP-1 and MIP-1 alpha levels in BAL fluid in patients with PF (r=-0.65, p=0.003; r=-0.48, p=0.04; respectively). CONCLUSION: Neutrophils alveolitis, presence of eosinophils, and higher concentrations of interleukin MCP-1, MIP-1 alpha, and MIP 1 beta in BAL fluid are associated with the development of fibrosis in SM victims. PMID- 17720293 TI - Temperature dependence of protein-hydration hydrodynamics by molecular dynamics simulations. AB - The dynamics of water molecules near the protein surface are different from those of bulk water and influence the structure and dynamics of the protein itself. To elucidate the temperature dependence hydration dynamics of water molecules, we present results from the molecular dynamic simulation of the water molecules surrounding two proteins (Carboxypeptidase inhibitor and Ovomucoid) at seven different temperatures (T=273 to 303 K, in increments of 5 K). Translational diffusion coefficients of the surface water and bulk water molecules were estimated from 2 ns molecular dynamics simulation trajectories. Temperature dependence of the estimated bulk water diffusion closely reflects the experimental values, while hydration water diffusion is retarded significantly due to the protein. Protein surface induced scaling of translational dynamics of the hydration waters is uniform over the temperature range studied, suggesting the importance protein-water interactions. PMID- 17720294 TI - Recreational benefits of urban forests: explaining visitors' willingness to pay in the context of the theory of planned behavior. AB - The extension of contingent valuation models with an attitude-behavior based framework has been proposed in order to improve the descriptive and predictive ability of the models. This study examines the potential of the theory of planned behavior to explain willingness to pay (WTP) in a contingent valuation survey of the recreational benefits of the Zurich city forests. Two aspects of WTP responses, protest votes and bid levels, were analyzed separately. In both steps, models with and without the psychological predictors proposed by the theory of planned behavior were compared. Whereas the inclusion of the psychological predictors significantly improved explanations of protest votes, their ability to improve the performance of the model explaining bid levels was limited. The results indicate that the interpretation of bid levels as behavioral intention may not be appropriate and that the potential of the theory of planned behavior to improve contingent valuation models depends on which aspect of WTP responses is examined. PMID- 17720295 TI - The concept of participatory local sustainability projects in seven Chinese villages. AB - SUCCESS was a scientific, multi-disciplinary case study of seven selected villages in China, coordinated by the Viennese research institute Oikodrom in which I have been a team member for 6 years. We assembled an international team of researchers to work together with local team leaders with the aim of involving village dwellers in a sustainability negotiation process. The project had a strong bottom-up approach, combined with top-down elements. Using participatory research methods, village teams discussed and developed ideas for concrete sustainability-oriented projects in their villages. By the end of the 3-year study of SUCCESS, equipped with the seeds of a multiple-scenario building process and the appropriate funding, each of the seven case study villages had generated ideas for local sustainability-oriented projects and put them into practice. The outcome of this participatory process is manifold. One major impact of the implementation of local projects was their visibility which was crucial for the village dwellers' confidence and their motivation to become engaged in a decision making process. The experience of their successful participation in a decision making process empowered them for self-organisation processes or a civil society process. The small projects offered interesting theoretical insights into how local contexts impact upon village dweller's decision on appropriate sustainability interventions. How they are as well in line with characteristics of different types of villages that were carried out within the study will be shown in this article. PMID- 17720296 TI - An exposimetry system using tissue-mimicking liquid. AB - Acoustic output measurements of diagnostic ultrasound scanners are currently performed in water and derated to approximate in situ values. The derating scheme ignores nonlinear propagation of sound waves and has been shown in previous numerical and experimental studies to tend to underestimate relevant pressure and intensity values in tissue mimicking media. This work describes an alternative method, which uses a tissue-mimicking liquid with attenuation coefficient slope of 0.3 dB/cm/MHz, speed of sound of 1,540 m/s and nonlinearity parameter B/A of 7.5. The acoustic properties of this liquid are stable for at least 2 y after production. Initial results using a single M-mode configuration are presented. These results confirm that derating can significantly underestimate the pulse intensity integral and peak rarefactional pressure. PMID- 17720297 TI - Intra-tumor flow index can predict the malignant potential of breast tumor: dependent on age and volume. AB - The aim of this study was to assess tumor vascularity through three dimensional (3D) power Doppler breast ultrasound (US) and propose a decision model for the classification of benign and malignant breast tumors. Patient recruitment for this study was performed consecutively during a 13-mo period (January 2003 to February 2004). A total of 102 benign and 93 malignant solid breast images were analyzed. Three-dimensional power Doppler US imaging was performed using a Voluson730 ultrasound system equipped with a relative stopping power index (RSP) 6 to 12 transducer. The Virtual Organ Computer-aided Analysis (VOCAL)-imaging program (version 2.1) was used to analyze the stored volume. Histogram indices of the vascularization index (VI), flow index (FI) and vascularization-flow index (VFI) for the intra-tumor and for shells with a thickness of 3 mm surrounding the breast lesion were calculated and showed that for both, malignancy had a higher VI, FI and VFI than benignancy, with statistical significance. Multivariate and stepwise logistic regression revealed the model (including patient age, volume and intra-tumor FI in 3D power Doppler vascularity) to be the best choice for malignant breast tumor characterization. The receiver operating characteristics (ROC) index for the performance of the model was 0.926. Histogram indices for the intra-tumor FI in the 3D power Doppler scan are a good choice of parameter for differentiating between malignant and benign tumors with respect to the power of sensitivity, no matter whether one index is suggested or the patients' age and volume are considered. PMID- 17720298 TI - Application of neural networks for the analysis of intravascular ultrasound and histological aortic wall appearance-an in vitro tissue characterization study. AB - The role of tissue characterization by intravascular ultrasound (IVUS) imaging of the aortic wall has not been well established. The artificial neural networks (ANNs) are a promising tool for image classification. The aim of the study was to assess the texture correlation between matching IVUS and histologic images of the aortic wall. The computer-based discrimination of pathology within the data sets was also evaluated. In vitro IVUS images and histologic sections from 36 aortic segments were compared using texture parameters that produced the best correlation or the highest discriminative value. The images were classified as normal or abnormal with variable degrees of pathology. Tissue characterization was performed by a nearest neighbor classifier, linear discriminant analysis (LDA) and the ANN-based approach. Good agreement was observed between IVUS and the histologic reference with a correlation coefficient of r = 0.89, r = 0.76 and r = 0.71 for the three most successful texture parameters. The ANN-based approach was the most effective in discriminant analysis, with a correct classification rate of 87.5% for histologic images and 79.2% for IVUS data. The study shows that ANNs are a potentially effective tool for assessment of IVUS aortic images. PMID- 17720299 TI - The antivascular action of physiotherapy ultrasound on a murine tumor: role of a microbubble contrast agent. AB - This study investigated whether a microbubble-containing ultrasound contrast agent had a role in the antivascular action of physiotherapy ultrasound on tumor neovasculature. Ultrasound images (B-mode and contrast-enhanced power Doppler [0.02 mL Definity]) were made of 22 murine melanomas (K1735(22)). The tumor was insonated (I(SATA) = 1.7 W cm(-2), 1 MHz, continuous output) for 3 min and the power Doppler observations of the pre- and postinsonation tumor vascularities were analyzed. Significant reductions (p = 0.005 for analyses of color-weighted fractional area) in vascularity occurred when a contrast-enhanced power Doppler study occurred before insonation. Vascularity was unchanged in tumors without a pretherapy Doppler study. Histologic studies revealed tissue structural changes that correlated with the ultrasound findings. The underlying etiology of the interaction between the physiotherapy ultrasound beam, the microbubble-containing contrast agent and the tumor neovasculature is unknown. It was concluded that contrast agents play an important role in the antivascular effects induced by physiotherapy ultrasound. PMID- 17720300 TI - Using the acoustic interference pattern to locate the focus of a high-intensity focused ultrasound (HIFU) transducer. AB - One of the main problems encountered when using conventional B-mode ultrasound (US) for targeting and monitoring purposes during ablation therapies employing high-intensity focused US (HIFU) is the appearance of strong interference in the obtained diagnostic US images. In this study, instead of avoiding the interference noise, we demonstrate how we used it to locate the focus of the HIFU transducer in both in vitro tissue-mimicking phantoms and an ex vivo tissue block. We found that when the B-mode image plane coincided with the HIFU focal plane, the interference noise was maximally converged and enhanced compared with the off-focus situations. Stronger interference noise was recorded when the angle (alpha) between the US image plane and the HIFU axis was less than or equal to 90 degrees. By intentionally creating a target (group of bubbles) at the 3.5-MHz HIFU focus (7.1 mm in length and 0.7 mm in diameter), the position of the maximal noise convergence coincided well with the target. The difference between the predicted focus and the actual one (bubbles) on x and z axes (axes perpendicular to the HIFU central axis, Fig. 1) were both about 0.9 mm. For y axis (HIFU central axis), the precision was within 1.0 mm. For tissue block ablation, the interference noise concentrated at the position of maximal heating of the HIFU induced lesions. The proposed method can also be used to predict the position of the HIFU focus by using a low intensity output scheme before permanent changes in the target tissue were made. PMID- 17720301 TI - Subharmonic response of encapsulated microbubbles: conditions for existence and amplification. AB - The response of encapsulated microbubbles at half the ultrasound insonation frequency, termed subharmonic response, may have potential applications in diagnosis and therapy. The subharmonic signal, emitted by Definity microbubble cloud sonicated by ultrasound was studied theoretically and experimentally. The size distribution of the microbubbles was optically analyzed and resonance frequency of 2.7 MHz was determined. An asymptotic model has been developed that generates subharmonic response of a single and of a cloud of bubbles of various sizes. Threshold conditions for existence and the intensity of the subharmonic signal are predicted to depend on microbubbles size distribution and shell properties, as well as on the driving field frequency and pressure. Thin tubes filled with Definity solution were insonated at acoustic pressures from 100 to 630 kPa. The intensities of the emitted fundamental harmonics and subharmonics were measured. At frequency 5.5MHz, twice the resonance frequency, the subharmonic signals were observed only at pressures greater than 190 kPa. The subharmonic to fundamental harmonics intensity ratio was within -12 to -1 dB. The experimental results showed good correlation with the theoretical results in the range of validity of the asymptotic solution, thus supporting the model assumptions. PMID- 17720302 TI - The neurovascular coupling bears properties of a feedforward and feedback regulative mechanism. AB - Temporal profiles of mediators involved in the neurovascular coupling bear feedforward and feedback characteristics, which are supported by mathematical modeling of evoked hemodynamic responses. However, cerebral autoregulation was expressed as a feedback control system. Therefore, question of overdetermination of the neurovascular coupling model arises. Addressing this issue, we analyzed both models for their appropriateness in describing the neurovascular coupling. Visually evoked flow velocities were recorded from healthy volunteers (aged 24.7 +/- 1.6 SD; 9 females, 11 males) with transcranial Doppler in the posterior cerebral artery. Control system parameters of the two models were specified according to the least-square-fitting technique. Mean square errors between measured and modeled curves and Akaike's information criterion (AIC) supported the feedforward-feedback model. Mean square differences decreased from 27.2 +/- 37.9 to 2.3 +/- 2 and the AIC from 2.7 +/- 0.6 %(2) to 2 +/- 0.3 %(2). The feedforward element increased the accuracy of the control system model in describing the fast initial response. Biologically, the parameter decreases the initial mismatch between the fast neuronal but slow vascular response because of visual activation. PMID- 17720303 TI - Mapping spatial and temporal changes in carotid atherosclerosis from three dimensional ultrasound images. AB - This study was designed to evaluate changes in carotid atherosclerosis using plaque and wall thickness maps derived from three-dimensional ultrasound (3DUS) images. Five subjects with carotid stenosis were scanned at baseline and 3 mo as part of a placebo-controlled intensive statin treatment study and three subjects with moderate atherosclerosis were scanned at baseline and again within 14 +/- 2 d. 3DUS-derived vessel wall volume (VWV) was measured using manual segmentation to provide segmentation contours that were used to generate scan and rescan carotid atherosclerosis thickness maps and thickness difference maps. There was no significant difference in VWV between scan and rescan for the three subjects scanned twice in 2 wk or the single subject treated with placebo. There was a significant difference between scan and rescan VWV for carotid stenosis subjects treated with atorvastatin (p < 0.001). Carotid atherosclerosis thickness difference maps showed visual qualitative evidence of thickness changes in vessel wall and plaque thickness in the common carotid artery for all statin-treated subjects and no change in a placebo-treated subject and subjects scanned twice in 2 wk. Carotid atherosclerosis thickness difference maps generated from 3DUS images provide evidence of vessel wall and plaque thickness changes for all subjects assessed. PMID- 17720304 TI - Extended and saturation prostatic biopsy in the diagnosis and characterisation of prostate cancer: a critical analysis of the literature. AB - OBJECTIVE: To review and critically analyse all the recent literature on the detection and characterisation of prostate cancer by means of extended and saturation protocols. METHODS: A systematic review of the literature was performed by searching MedLine from January 1995 to April 2007. Electronic searches were limited to the English language, and the key words "prostate cancer," "diagnosis," "transrectal ultrasound (TRUS)," "prostate biopsy," and "prognosis" were used. RESULTS: The prostate biopsy technique has changed significantly since the original Hodge sextant biopsy protocol. Several types of local anaesthesia are now available, but periprostatic nerve block (PPNB) has proved to be the most effective method to reduce pain during TRUS biopsy. It remains controversial whether PPNB should be associated with other medications. The optimal extended protocol (sextant template with at least four additional cores) should include six standard sextant biopsies, with additional biopsies (up to 12 cores) taken more laterally (anterior horn) to the base and medially to the apex. Repeat biopsies should be based on saturation biopsies (number of cores >/= 20) and should include the transition zone, especially in a patient with an initial negative biopsy. As a means of increasing accuracy of prostatic biopsy and reducing unnecessary prostate biopsy, colour and power Doppler imaging, with or without contrast enhancement, and elastography now can be successfully adopted, but their routine use is still controversial. CONCLUSION: Extended and saturation biopsy schemes should be performed at first and repeat biopsy, respectively. The widespread use of local anaesthesia makes the procedures more comfortable. PMID- 17720305 TI - PSA and prostate cancer screening: the challenge of the new millennium. PMID- 17720307 TI - Predator-prey dynamics in P systems ruled by metabolic algorithm. AB - P systems are used to compute predator-prey dynamics expressed in the traditional formulation by Lotka and Volterra. By governing the action of the transition rules in such systems using the regulatory features of the metabolic algorithm we come up with simulations of the Lotka-Volterra equations, whose robustness is comparable to that obtained using Runge-Kutta schemes and Gillespie's Stochastic Simulation Algorithm. Besides their reliability, the results obtained using the metabolic algorithm on top of P systems have a clear biochemical interpretation concerning the role, of reactants or promoters, of the species involved. PMID- 17720309 TI - Sorption behavior of cesium on various soils under different pH levels. AB - In the present study we investigated the sorption behavior of Cs in four different soils (sandyloam, loam, clayloam and clay) by using batch experiment. Cs sorption characteristics of the studied soils were examined at 4 mgL(-1) Cs concentration, at various pH levels, at room temperature and with 0.01 M CaCl(2) as a background electrolyte. Among different soils the decrease of k(d) (distribution coefficient) of cesium, at all pH levels, followed the sequence sandyloam > loam > clayloam > clay, indicating that the particle size fractions and especially the clay content plays predominant role on sorption of Cs. The effect of pH on cesium sorption displays a similar pattern for all soils, depending on soil type. At acid pH levels less cesium was sorbed, due to a greater competition with other cations for available sorption sites. The maximum sorption of Cs was observed at pH 8, where the negative charge density on the surface of the absorbents was the highest. For all soils was observed significantly lower Cs sorption at pH 10. PMID- 17720308 TI - Reduced expression of RASSF1A in esophageal and nasopharyngeal carcinomas significantly correlates with tumor stage. AB - Reduced expression or loss of tumor suppressor genes play a key role in many cancers. In this study, we investigated the role of RASSF1A in the pathogenesis of esophageal squamous cell carcinoma (ESCC) and nasopharyngeal carcinoma (NPC). We detected the down-regulated expression of both RASSF1A transcripts and protein in tumor tissues using RT-PCR and tissue microarray immunohistochemical staining analyses. Down-regulated expression of RASSF1A showed a significant association with WHO grade, tumor status, and lymph node metastasis, showing its possible utility as a biomarker for clinical specimens. PMID- 17720310 TI - Adsorptive removal of acrylonitrile by commercial grade activated carbon: kinetics, equilibrium and thermodynamics. AB - The potential of activated carbons--powdered (PAC) and granular (GAC), for the adsorption of acrylonitrile (AN) at different initial AN concentrations (500.9927) within test ranges. The method developed showed good precision and accuracy with overall intra- and inter-day variations of 0.64-4.79% and 0.69 4.96%, respectively, and the overall recoveries of 93.50-107.69% for the 12 compounds analyzed. This method was successfully applied to quantify the twelve components in ten commercial samples from three formulas by seven independent manufacturers. This readily available, low-cost and reliable HPLC-DAD-ELSD method improved the quality control of traditional Chinese medicinal preparations consisting of complex compounds with different structures such as FDPs. PMID- 17720350 TI - LEADER surveillance program results for 2006: an activity and spectrum analysis of linezolid using clinical isolates from the United States (50 medical centers). AB - Surveillance for emerging linezolid resistance among commonly occurring Gram positive pathogens in the United States began with the 2002 ZAAPS program and more recently (2004) expanded as the LEADER program. The 2006 LEADER program processed 5374 strains from 50 medical centers (100 per site) located within the 9 US census regions; species and number tested by broth microdilution (% linezolid susceptible) included Staphylococcus aureus (2913, >99.9), coagulase negative staphylococci (CoNSs) (808, 98.4), enterococci (547, 97.4), Streptococcus pneumoniae (546, 100.0), viridans group streptococci (189, 100.0), and beta-hemolytic streptococci (371, 100.0). In addition to 1 linezolid nonsusceptible S. aureus, 3 strains were daptomycin-nonsusceptible, 4 were quinupristin/dalfopristin-intermediate, 2 were vancomycin-intermediate (vancomycin MIC values, 4 mug/mL), and all were methicillin-resistant S. aureus. Among the linezolid-resistant isolates (1 S. aureus, 13 CoNSs, 3 Enterococcus faecalis, and 10 Enterococcus faecium isolates), all but 3 Staphylococcus epidermidis isolates had the G2567T mutation. Overall, 99.55% of the tested 2006 LEADER program isolates remained susceptible to linezolid at current Clinical and Laboratory Standards Institute breakpoints. PMID- 17720351 TI - A comparison of knowledge of diabetes mellitus between patients with diabetes and healthy adults: a survey from north Malaysia. AB - OBJECTIVE: The primary objective of this study was to assess and compare the knowledge of diabetes mellitus possessed by patients with diabetes and healthy adult volunteers in Penang, Malaysia. METHOD: A cross-sectional study was conducted from 20 February 2006 to 31 March 2006. We randomly selected 120 patients with diabetes mellitus from a diabetic clinic at the General Hospital Penang, Malaysia and 120 healthy adults at a shopping complex in Penang. Each participant was interviewed face-to-face by a pharmacist using a validated questionnaire, and they were required to answer a total of 30 questions concerning knowledge about diabetes mellitus using Yes, No or Unsure as the only response. RESULTS: The results showed that patients with diabetes mellitus were significantly more knowledgeable than the healthy volunteers about risk factors, symptoms, chronic complications, treatment and self-management, and monitoring parameters. Educational level was the best predictive factor for diabetes mellitus and public awareness. CONCLUSION: Knowledge about diabetes mellitus should be improved among the general population. PRACTICE IMPLICATIONS: This study has major implications for the design of an educational programme for diabetics and a health promotion programme as a primary prevention measure for the healthy population in general, and especially for those at high risk. The results could be useful in the design of future studies for evaluating patients' and the general public's knowledge about diabetes mellitus. PMID- 17720352 TI - Identification of interspecies concordance of mechanisms of arsenic-induced bladder cancer. AB - Exposure to arsenic causes cancer by inducing a variety of responses that affect the expression of genes associated with numerous biological pathways leading to altered cell growth and proliferation, signaling, apoptosis and oxidative stress response. Affymetrix GeneChip arrays were used to detect gene expression changes following dimethylarsinic acid (DMA) exposure to human bladder cells (UROtsa) or rat bladder cells (MYP3) and rat bladder epithelium in vivo at comparable doses. Using different experimental models coupled with transcriptional profiling allowed investigation of the correlation of mechanisms of DMA-induced toxicity between in vitro and in vivo treatment and across species. Our observations suggest that DMA-induced gene expression in UROtsa cells is distinct from that observed in the MYP3 cells. Principal component analysis shows a more distinct separation by treatment and dose in MYP3 cells as compared to UROtsa cells. However, at the level of pathways and biological networks, DMA affects both common and unique processes in the bladder transitional cells of human and rats. Twelve pathways were found common between human in vitro, rat in vitro and rat in vivo systems. These included signaling pathways involved in adhesion, cellular growth and differentiation. Fifty-five genes found to be commonly expressed between rat in vivo and rat in vitro systems were involved in diverse functions such as cell cycle regulation, lipid metabolism and protein degradation. Many of the genes, processes and pathways have previously been associated with arsenic induced toxicity. Our finding reiterates and also identifies new biological processes that might provide more information regarding the mechanisms of DMA induced toxicity. The results of our analysis further suggest that gene expression profiles can address pertinent issues of relevance to risk assessment, namely interspecies extrapolation of mechanistic information as well as comparison of in vitro to in vivo response. PMID- 17720354 TI - Abdominal adiposity and cardiometabolic risk: do we have all the answers? AB - Overweight and obesity, particularly abdominal adiposity, increase the risk for type 2 diabetes mellitus and cardiovascular disease (CVD). Metabolic syndrome, a constellation of risk factors that includes elevated triglycerides, low high density lipoprotein cholesterol, elevated blood pressure, elevated fasting glucose, and abdominal obesity, predicts the development of CVD and diabetes to an even greater degree. Excess abdominal adipose tissue is associated with insulin resistance, the precursor to type 2 diabetes, and creates an atherogenic inflammatory milieu, characterized by high levels of C-reactive protein and other inflammatory markers (e.g., fibrinogen, plasminogen activator inhibitor-1, cytokines, and adhesion molecules). High levels of these biomarkers correlate with an increased incidence of diabetes and CVD. Recent evidence suggests that patients with nonalcoholic fatty liver disease have an increased incidence of obesity, metabolic syndrome, and insulin resistance and/or type 2 diabetes. Relatively small reductions in body weight may significantly reduce abdominal adipose tissue, reduce insulin resistance, lower triglycerides and low-density lipoprotein cholesterol, reduce inflammation, and decrease overall cardiometabolic risk. PMID- 17720356 TI - Understanding metabolic homeostasis and imbalance: what is the role of the endocannabinoid system? AB - Endogenous endocannabinoids (ECs) (anandamide and 2-arachidonoyl glycerol) are part of the leptin-regulated neural circuitry involved in appetite regulation. One of the sites of the orexigenic action of ECs involves activation of cannabinoid-1 (CB1) receptors in the lateral hypothalamus, from which neurons involved in mediating food reward project into the limbic system. In animal models of obesity, pharmacologic blockade or genetic ablation of CB1 receptors causes a transient reduction in food intake accompanied by sustained weight loss, reduced adiposity, and reversal of hormonal/metabolic changes, such as elevated levels of plasma leptin, insulin, glucose, and triglyceride, and reduced levels of plasma adiponectin (Acrp30). However, the beneficial effects of CB1 blockade on weight and metabolism cannot be explained by appetite suppression alone. Animal studies suggest that CB1 blockade exerts a direct peripheral as well as a central effect on fat metabolism. CB1 receptor blockade with rimonabant has been shown to not only reduce weight and adiposity but also to directly modulate fat metabolism at peripheral sites in skeletal muscle, adipose tissue, and the liver. Preclinical animal studies suggest that CB1 blockade acts on adipocytes to increase Acrp30 expression, on hepatocytes to decrease de novo lipogenesis and increase fatty acid oxidation, and on skeletal muscle to reduce blood glucose and insulin levels. Extrapolating from animal studies to the clinic, CB1 receptor blockade offers a promising strategy not only for reducing weight and abdominal adiposity but also for preventing and reversing its metabolic consequences. PMID- 17720358 TI - What is the potential role of cannabinoid-1 receptor blockade in glucose and lipid management? AB - Interventions that reduce weight and abdominal adiposity have been shown to improve obesity-associated disorders of glucose and lipid metabolism, reduce blood pressure, and promote other beneficial effects on cardiometabolic risk parameters. When long-term adherence to diet/exercise recommendations is suboptimal, management of overweight and obese patients at high cardiometabolic risk includes the use of adjunctive pharmacologic agents to facilitate weight loss and weight loss maintenance. Rimonabant, a cannabinoid-1 (CB1) receptor blocker, has been shown to induce weight loss and improve cardiometabolic parameters, implying that the endocannabinoid system is a promising target for obesity-related health improvement. Herein we summarize the results of the Rimonabant in Obesity (RIO) studies, which have evaluated the effectiveness of CB1 receptor blockade in facilitating weight loss and improving cardiometabolic health in >6,600 patients from the United States and Europe. As compared with placebo, 20 mg/day of rimonabant consistently produced greater reductions in weight and waist circumference, as well as improvements in dyslipidemia and parameters of glucose metabolism. The improvements that were noted for several cardiometabolic parameters with rimonabant were greater than what would be expected from the weight loss alone, suggesting there may be an independent effect of the drug on metabolic function. The results of these studies suggest that CB1 receptor blockade may be a useful treatment for multiple cardiometabolic risk factors in overweight and obese patients. PMID- 17720359 TI - Cardiovascular and metabolic risk factors: how can we improve outcomes in the high-risk patient? AB - Risk assessment algorithms, such as that used in the third Adult Treatment Panel (ATP III) of the National Cholesterol Education Program (NCEP) for treating low density lipoprotein cholesterol, can be used to classify patients' risk for cardiovascular and metabolic problems and to determine the appropriate level of therapeutic intervention. Patients at highest risk should receive the most intensive therapy. The presence of the metabolic syndrome, a clustering of atherogenic risk factors including dyslipidemia, elevated blood pressure, elevated blood glucose, and other problems, confers additional risk for diabetes mellitus and atherosclerotic cardiovascular disease at every level of risk. Pharmacotherapy with lipid-lowering, antiplatelet, antihypertensive, or insulin sensitizing agents to modify specific risk factors is indicated in patients at higher risk, but lifestyle change (e.g., smoking cessation, weight reduction, increased physical activity, and "heart-healthy" dietary modifications) and blood pressure control can be used across all categories of risk. PMID- 17720362 TI - Repeated exercise in mice alters expression of IL-10 and TNF-alpha in intestinal lymphocytes. AB - Intestinal inflammation is characterized by mucosal damage that may arise, in part, to imbalances in pro- and anti-inflammatory cytokines. The purpose of this study was to describe the effects of repeated bouts of strenuous exercise on cytokine expression in mouse intestinal lymphocytes (IL). Thirty-four female C57BL/6 mice were randomly assigned to three groups: three repeated bouts of treadmill running separated by 24h followed by sacrifice immediately or after a 24h period or a sedentary (no exercise) control. The pro-inflammatory cytokine, TNF-alpha, and the anti-inflammatory cytokine, IL-10, were measured in IL by Western blotting. IL-10 concentration increased by 48% (p<0.05) in the immediate group compared to the sedentary control. TNF-alpha levels in mouse IL were significantly lower 24h after completion of the exercise protocol compared to the immediate group (p<0.05). The results suggest a possible physiological compensation in which intestinal lymphocytes increase the expression of IL-10 in response to exercise-induced stress. PMID- 17720365 TI - Journal ethics. PMID- 17720364 TI - Stability of Cohen-Grossberg neural networks with time-varying delays. AB - In this paper, we investigate the existence and stability of the equilibrium point of Cohen-Grossberg neural networks with time-varying delays. Under easily verified conditions, exponential stability is obtained when the delay is finite, while asymptotic stability is obtained when the delay is infinite. Moreover, the stability obtained is robust. The only condition for the delay term is continuity. The results obtained here improve and extend to those in the literature. PMID- 17720366 TI - Obesity and stroke after cardiac surgery: the impact of grouping body mass index. PMID- 17720367 TI - A surgeon operates on his son: wisdom or hubris? PMID- 17720368 TI - Mid-term clinical results using a tissue-engineered pulmonary valve to reconstruct the right ventricular outflow tract during the Ross procedure. AB - BACKGROUND: The Ross procedure is mainly limited by the durability of the valve prostheses used to reconstruct the right ventricular outflow tract. This study was performed to collect prospective safety and effectiveness data of the Ross procedure using a tissue-engineered heart valve to reconstruct the right ventricular outflow tract. METHODS: Between May 2000 and February 2003, 23 patients received tissue-engineered heart valves. Two to four weeks before the Ross operation, a piece of forearm or saphenous vein was harvested to isolate, characterize, and expand endothelial cells. A pulmonary allograft (n = 11) or xenograft (n = 12) was decellularized, coated with fibronectin, and seeded with autologous vascular endothelial cells, using a specially developed bioreactor. Follow-up was performed by clinical evaluation, transthoracic echocardiography, magnetic resonance imaging, and multislice computed tomography. RESULTS: The patient mean age was 44.0 +/- 13.7 years. Cell seeding density was 1.1 x 10(5) +/ 0.5 x 10(5) cells/cm2, with a viability of 90.2% +/- 8.9%. All patients survived the operation. One patient died during follow-up, and 1 patient required reoperation. All surviving patients are currently in New York Heart Association functional class I. Transthoracic echocardiographic evaluation of the tissue engineered heart valve showed a mean flow velocity of 0.9 +/- 0.4 m/s at 5 years. Multislice computed tomography showed no calcification up to 5 years postoperatively. CONCLUSIONS: Tissue-engineered heart valves showed excellent hemodynamic performance during mid-term follow-up. Decellularization of heart valves and seeding with autologous vascular endothelial cells may prevent tissue degeneration and improve valve durability. PMID- 17720369 TI - Stentless aortic valve reoperations: a surgical challenge. AB - BACKGROUND: Stentless aortic valve reoperations may become more common as these bioprostheses reach the limits of their durability. Relatively few studies have examined stentless valve reoperation, and we therefore reviewed our results for these procedures. METHODS: All patients with stentless valves undergoing redo aortic valve replacement (AVR) at our institution were examined (n = 57). Ten patients had a prior Freestyle valve (Medtronic, Minneapolis, MN), and 47 patients had a Toronto stentless porcine valve (SPV; St. Jude Medical St Paul, MN). RESULTS: Redo AVR was performed 8.4 +/- 3.7 years (range, 0.1 to 16.5 years) after stentless valve implantation. Reoperations were elective in 27 patients (49%), and 30 (51%) underwent urgent or emergency procedures. The indication for redo AVR was structural valve dysfunction in 48 patients (84%), acute endocarditis in 7 (12%), and other in 2 (4%). Aortic insufficiency was present in 47 patients (82%). A total of 36 aortic root replacement operations (63% of patients) were required, of which 19 were secondary to severe adhesions between the stentless valve and the native aortic root. Operative mortality was 11% (n = 6) for the entire group. Mortality was higher in patients undergoing redo AVR less than 1 year after stentless valve implantation versus more than 1 year (67% versus 7%, p = 0.03). Long-term survival at 5 years postoperatively was 79% +/- 7% in all patients, and 81% of survivors were in New York Heart Association class I or II. CONCLUSIONS: Reoperation after stentless AVR is a challenging procedure that frequently requires aortic root replacement. Stentless valve reoperation is associated with an increased risk of death, particularly in patients operated on within 1 year of implantation. PMID- 17720370 TI - A prospective study of predicting factors in ischemic mitral regurgitation recurrence after ring annuloplasty. AB - BACKGROUND: Ischemic mitral regurgitation (IMR) is a complex lesion to repair, and its successful management requires an understanding of its mechanism and severity. Ring annuloplasty, currently the surgical treatment of choice for IMR, has failure rates as high as 30% in patients with functional IMR. We sought to study the variables that can predict IMR recurrence after ring annuloplasty. METHODS: This is a prospective study of 114 patients with 3+ to 4+ IMR who underwent coronary artery bypass grafting and mitral valve annuloplasty with acceptable results at an approximately 2-year follow-up. Variables were compared in a failure group, comprising patients with 2+ or higher MR and a nonfailure group, consisting of those with less than +2 MR. RESULTS: There were five postoperative in-hospital deaths. During follow-up, 14 patients died and 95 patients were evaluated. After a mean follow-up of 22.2 +/- 4.6 months for the nonfailure group and 18.6 +/- 5.6 months for the failure group, 23 patients (24.4%) exhibited annuloplasty failure. Some variables had an effect in our univariate analysis, but only interpapillary muscle distance had a relationship with recurrent MR in the multivariate analysis. Mean preoperative interpapillary muscle distance was 15.0 +/- 4.0 and 26.5 +/- 2.9 in the nonfailure group and failure group, respectively (p < 0.0001). CONCLUSIONS: Interpapillary muscle distance, as a reliable index of dysfunctional subvalvular apparatus in patients with IMR, can predict late postrepair MR and indicate the need for a procedure complementary to annuloplasty. PMID- 17720371 TI - A change in perspective: results for ischemic mitral valve repair are similar to mitral valve repair for degenerative disease. AB - BACKGROUND: Although the benefits of mitral valve repair for degenerative disease are well established, many consider surgery for functional ischemic mitral regurgitation (MR) less amenable to operative treatment. We hypothesized that mitral valve repair for ischemic MR results in outcomes similar to those for mitral valve repair for degenerative MR. METHODS: Retrospective review of nonemergent mitral valve repairs for an 8-year period revealed 105 patients with functional ischemic MR, of whom 39 were treated for severe tethering (ischemic group), and 245 patients with degenerative MR (degenerative group). RESULTS: Patients in the ischemic group had more comorbidities (p < 0.01) and worse preoperative left ventricular dysfunction (ejection fraction < or = 0.29) compared with patients in the degenerative group; (ischemic, 37.1% [39 of 105] versus degenerative, 2.0% [5 of 245]; p < 0.01). Immediate postrepair transesophageal echocardiogram revealed a 0 to 1+ MR in all patients in both groups (not significant). The hospital mortality rate was 1.9% (2 of 105) in the ischemic group and 1.2% (3 of 245) in the degenerative group (p = 1.00). The 5 year survival rate was 83.9% in the ischemic group and 94.3% in the degenerative group (p < 0.01). Five-year freedom from reoperation for recurrent MR was 100% and 97.5% in the ischemic and degenerative groups, respectively (p = 0.14). Postoperative renal failure and stroke rates were similar between both groups (not significant). The incidence of moderate or greater MR after more than 1 year of follow-up was similar between groups (not significant). CONCLUSIONS: Despite the multiple comorbidities that afflict patients with ischemic MR, mitral valve repair for ischemic and degenerative disease produces comparable and satisfactory outcomes. An aggressive approach to repair of functional ischemic MR, including treatment of tethering, leads to durable results. PMID- 17720372 TI - Straight deep hypothermic arrest: experience in 394 patients supports its effectiveness as a sole means of brain preservation. AB - BACKGROUND: The three methods of brain preservation for aortic arch surgery- straight deep hypothermic circulatory arrest (DHCA) without perfusion adjuncts, retrograde cerebral perfusion, and antegrade cerebral perfusion--remain controversial. Patients in this report underwent surgery solely with DHCA. METHODS: Straight DHCA at 19 degrees C was used in 394 patients (267 males, 127 females) during a 10-year period. Mean age was 61.3 years (range, 15 to 88 years). Eighty-seven cases (22.1%) were urgent or emergencies. Thirty-eight (9.6%) were performed for descending or thoracoabdominal pathology and the rest for ascending/arch (102 hemiarch, 49 total arch). Ninety-one patients (23.1%) had dissections. The head was packed in ice. No barbiturate coma was used. RESULTS: DHCA lasted a mean of 31.0 minutes (range, 10 to 66 minutes). Reexploration for bleeding was required in 4.5% (18/394). Overall mortality was 6.3% (25/394). Mortality was 3.6% (11/307) for elective cases and 16% (14/87) for emergency cases. The stroke rate was 4.8% (19/394). The seizure rate was 3.1% (12/394). Forty-five patients with high professional cognitive demands (MD, PhD, attorney, etc) performed without detriment postoperatively. Among patients with DHCA exceeding 40 minutes, the stroke rate was 13.1% (8/61); a neuroradiologist's review of brain computed tomography scans found 62.5% of these strokes (5/8) to be embolic and 37.5% (3/8) hypoperfusion related. By multivariable logistic regression, emergency operation and descending location increased morbidity and mortality. CONCLUSIONS: Straight DHCA without adjunctive perfusion suffices as a sole means of cerebral protection. Stroke and seizure rates are low. Cognitive function, by clinical assessment, is excellent. Especially for straightforward ascending/arch reconstructions, there is little need for the added complexity of brain perfusion strategies. PMID- 17720373 TI - Perfusing the cold brain: optimal neuroprotection for aortic surgery. AB - BACKGROUND: Selective cerebral perfusion (SCP) may enhance the neuroprotective benefits of hypothermia during aortic surgery. However, despite its widespread adoption, there is no consensus regarding optimal implementation of SCP. We used a survival porcine model to explore the physiologic characteristics and behavioral benefits of various protocols involving hypothermic circulatory arrest (HCA) and SCP. METHODS: Thirty pigs (26.3 +/- 1.4 kg), cooled to 15 degrees C on cardiopulmonary bypass, using alpha-stat pH management (mean hematocrit 30%), were randomly allocated to differing brain protection strategies: 90 minutes of HCA (group A); 30 minutes of HCA, then 60 minutes of SCP (group B); or 90 minutes of SCP (group C). Using fluorescent microspheres and sagittal sinus sampling, cerebral blood flow (CBF [mL x 100g(-1) x min(-1)]) and cerebral metabolic rate for oxygen (CMRO2 [mL x 100g(-1) x min(-1)]) were assessed at baseline, after cooling, during SCP (where applicable), and for 2 hours after cardiopulmonary bypass. Neurobehavioral scores were assessed blindly from standardized videotaped sessions for 7 days postoperatively. RESULTS: Cerebral blood flow was significantly higher (p = 0.0001) during SCP (60 and 90 minutes) if preceded by HCA. The CMRO2 was also significantly higher in group B versus group C (p = 0.016) at 60 minutes. The CMRO2 in all three groups rebounded promptly toward baseline after weaning from cardiopulmonary bypass. Postoperative neurobehavioral scores were significantly worse in group A. CONCLUSIONS: Continuous SCP provides the best brain protection overall. However, an initial period of HCA does not seem to impair late outcome; perhaps the elevated CBF and CMRO2 observed reflect a beneficial cerebral response to a recoverable insult. Clearly, 90 minutes of HCA induces permanent brain injury, even in this carefully controlled setting. PMID- 17720374 TI - Aortic root replacement does not affect outcome and quality of life. AB - BACKGROUND: Different studies have analyzed the potential impact of the underlying pathologic process and the use of deep hypothermic circulatory arrest on outcome and quality of life after surgery on the thoracic aorta. The aim of this study is to analyze the impact of different surgical procedures on outcome and quality of life. METHODS: Between June 2001 and December 2003, 244 patients underwent surgery for various diseases of the ascending aorta with or without involvement of the aortic valve or root. They were divided according to the operative procedure: 76 patients (31.2%) underwent isolated replacement of the ascending aorta, 42 patients (17.2%) received separate aortic valve replacement and supracoronary replacement of the ascending aorta, 86 patients (35.2%) received a mechanical composite graft, and 40 patients (16.4%) received a biologic composite graft. All in-hospital data were assessed, and a follow-up was performed in all survivors after 26.6 +/- 8.8 months, focusing on outcome and quality of life (SF-36). RESULTS: Overall in-hospital mortality was 6.1%, and late mortality was 5.7%, with no significant difference between groups. Independent of the surgical technique and the extent of surgery, there was no difference in quality of life between the surgical collective and an age-matched and sex-matched standard population. CONCLUSIONS: Operations of the ascending aorta and aortic valve are very safe, with low in-hospital mortality and favorable midterm outcome regarding late mortality and morbidity. Quality of life after operations of the ascending aorta and aortic valve is equal to a standard population and is not affected by the surgical procedure. Liberal use of aortic root replacement is therefore justified to radically treat the diseased aortic segment. PMID- 17720375 TI - Role of somatosensory evoked potentials in predicting outcome during thoracoabdominal aortic repair. AB - BACKGROUND: Clinical utility of somatosensory evoked potentials (SSEP) in descending thoracic and thoracoabdominal aortic repair is debated. We reviewed our practical experience with SSEP in descending thoracic and thoracoabdominal aortic repairs. METHODS: Between January 2000 and April 2005, we used SSEP monitoring in 444 patients (270 thoracoabdominal aorta and 174 descending thoracic aorta). Median age was 68 years; 36% were female. Only changes of spinal origin were analyzed. Changes were classified as (1) no change, (2) transient changes that returned to baseline by the end of the procedure, or (3) persistent changes that did not return to baseline by the end of the procedure. RESULTS: Somatosensory evoked potential changes occurred in 87 (19.6%) patients; 22 (25%) of these did not return to baseline. Immediate neurologic deficit occurred in 8 of 444 patients (1.8%); five deficits (5 of 87; 5.8%) occurred in patients with SSEP changes, compared with three deficits (3 of 357; 0.8%) in patients without changes. Odds ratio for this comparison was 7.2 (p < 0.002). Somatosensory evoked potential was a poor screening tool for neurologic deficit, with a sensitivity of 62.5% and specificity 81.2%. Negative predictive value was 99.2%, indicating a very low event probability in the absence of SSEP changes. Delayed neurologic deficit occurred in 3.2% and was not related to SSEP changes. Somatosensory evoked potential changes were also associated with increased 30-day mortality and low glomerular filtration rate. CONCLUSIONS: Intraoperative SSEP monitoring was reliable in ruling out spinal injury in descending thoracic and thoracoabdominal aortic repair, but had a low sensitivity. It did not predict delayed neurologic deficit. Spinal SSEP change was an independent predictor of mortality and correlated with low preoperative glomerular filtration rate. PMID- 17720376 TI - Preservation of spinal cord function after extensive segmental artery sacrifice: regional variations in perfusion. AB - BACKGROUND: Sacrifice of intercostal and lumbar arteries simplifies thoracoabdominal aneurysm surgery and enables endovascular stenting. Little is known about alterations in cord perfusion after extensive segmental artery sacrifice. We explored this question using hypothermia to reduce metabolism. METHODS: Twelve juvenile Yorkshire pigs (mean weight, 22.3 kg) were randomized to segmental artery sacrifice at 32 degrees C or 37 degrees C. Cord integrity was assessed with myogenic-evoked potential (MEP) monitoring. Stepwise craniocaudal sacrifice of segmental arteries was continued until MEP diminution occurred; the last segmental artery was then reopened. Fluorescent microspheres were used to measure spinal cord blood flow (SCBF) at baseline, 5 minutes, 1 hour, and 3 hours after segmental artery sacrifice. Hind limb function was monitored for 5 days. RESULTS: All animals recovered normal hind limb function. At 32 degrees C, more segmental arteries, 16.5 versus 15 (p = 0.03), could be sacrificed without MEP loss. Baseline SCBF at 32 degrees C was 50% that at 37 degrees C (p = 0.003) and remained fairly stable throughout. At 37 degrees C, SCBF to the craniocaudal extremes of the cord (C1 to T3 and L2 to L6) increased markedly (p = 0.01) at 1 hour and returned toward normal at 3 hours. Concomitantly, SCBF fell in the middle portion of the cord (T9 to T13) at 1 hour before returning to normal at 3 hours. CONCLUSIONS: Almost all segmental arteries can be sacrificed with preservation of spinal cord function. No major change occurs in the central cord in normothermic animals, but there is significant transient hyperemia in segments adjacent to extrasegmental vessels. Hypothermia reduces SCBF and abolishes this possible steal phenomenon. Metabolic and hemodynamic manipulation should enable routine sacrifice of all segmental arteries without spinal cord injury. PMID- 17720377 TI - Contemporary coronary graft patency: 5-year observational data from a randomized trial of conduits. AB - BACKGROUND: The Radial Artery Patency and Clinical Outcomes (RAPCO) study has enrolled patients into two trials to compare the radial artery with the free right internal thoracic artery (if age <70 years) or with saphenous vein (if age >70 years) when grafted onto the largest target other than the left anterior descending artery. Patency outcomes in RAPCO will focus only on the trial graft in each case. However, postoperative angiography from this ongoing study has reassessed all coronary grafts, both trial and nontrial: together these offer a valuable observational overview of likely graft patency in the current era in predominately asymptomatic patients, in contrast to symptom-directed studies that may overestimate the incidence of graft failure. METHODS: Protocol-directed percutaneous angiography has been performed at intervals weighted toward the end of the study period, or earlier when directed by symptoms. To date, 184 patients have been studied as per protocol, at time points up to 10 years (mean, 3.9), among whom there are 430 nontrial grafts in addition to the 184 trial grafts. Supplementary angiography (percutaneous or computed tomography) was offered at a fixed 5-year time point postoperatively: at this juncture, 193 trial grafts and 469 nontrial grafts have been imaged. Three masked investigators report grafts as angiographically successful if patent from proximal to distal anastomosis inclusive. Failed grafts include greater than 80% stenosis, string sign, or occlusion. RESULTS: In staggered protocol-directed angiography, overall patency of the in-situ internal thoracic artery grafts and free arterial grafts was 95.5% (210 of 220) and 91.4%% (150 of 164), respectively, which did not differ significantly (p = 0.13). Saphenous vein graft patency was 83.0% (191 of 230) with a trend to higher failure rate compared with free arterial grafts (p = 0.07), and was significantly lower than that of in-situ internal thoracic artery grafts (p = 0.01). At the optional 5-year time point, outcomes are similar to the protocol-directed findings, with patency of in-situ left and right internal thoracic artery grafts of 95.8% (204 of 213), which was significantly greater than that of the other two groups (p = 0.02 and p < 0.001). Patency of free arterial conduits and saphenous vein grafts was 89.1% (139 of 156) and 82.4% (201 of 244), respectively, which did not differ significantly (p = 0.09) at 5 years. CONCLUSIONS: Although trending to superior patency compared with vein grafts, free arterial conduits have not matched the gold standard achieved by in-situ internal thoracic arteries at trial midpoint. Until the results from RAPCO are available, which will test types of free arterial graft against each other and will compare radial and vein grafts in the longer term, these observational data justify for now our current practice of maximal use of in-situ conduits supplemented by free radial grafts. PMID- 17720378 TI - Invited commentary. PMID- 17720379 TI - Epicardial ultrasonography: a potential method for intraoperative quality assessment of coronary bypass anastomoses? AB - BACKGROUND: Intraoperative quality assessment in coronary artery bypass surgery confirms graft patency and enables revision of failing grafts. The aim of this study was to evaluate graft quality intraoperatively by epicardial ultrasonography and to compare this technique with transit time flow measurements and intraoperative angiography, and to evaluate the ability of these methods to predict long-term patency as described by follow-up angiography. METHODS: Thirty nine patients with mean age of 66 years (SD 9.5) who underwent off-pump coronary artery bypass surgery with internal mammary artery graft to the left anterior descending coronary artery were included. Epicardial ultrasonography and transit time flow measurement were performed after completion of the anastomoses, and coronary angiography after closure of the chest. Follow-up angiography was carried out after 156 days (SD 50). RESULTS: Diameter measurements obtained by epicardial ultrasonography correlated poorly with the same diameter measurements obtained by angiography. Epicardial ultrasonography revealed 5 abnormal grafts (13%), transit time flow measurements none, and intraoperative angiography 9 (23%). At follow-up angiography, 4 grafts (11%) were pathologic. Epicardial ultrasonography and transit time flow measurements indicated no need for graft revision; intraoperative angiography suggested need for revision in 3 cases. CONCLUSIONS: Epicardial ultrasonography could be a useful method for intraoperative assessment of graft anastomosis quality, but needs to demonstrate its ability to predict grafts in need of revision. Angiography must be considered the gold standard in intraoperative imaging. PMID- 17720380 TI - Results and predictors of early and late outcome of coronary artery bypass grafting in patients with severely depressed left ventricular function. AB - BACKGROUND: Coronary artery bypass grafting (CABG) is a well-accepted therapeutic approach in patients with symptomatic multivessel coronary artery disease and severely depressed left ventricular function. However, the potential impact of off-pump CABG in this group of patients remains unknown. In addition, there are only scarce data regarding long-term survival and its predictors in this patient population. METHODS: We retrospectively analyzed prospectively collected data of 2,725 consecutive patients (mean age, 65 +/- 11 years; 843 (31%) female) undergoing CABG between January 1998 and December 2005 (ejection fraction [EF] < or = 0.30; n = 495, 18%). Outcome measures included hospital mortality, major complications, and long-term survival. Multivariate analysis was performed to identify predictors of hospital mortality and late survival. Subgroup analysis for patients with EF less than or equal to 0.30 undergoing conventional CABG (n = 424, 86%) versus off-pump CABG (n = 71, 14%) was performed. RESULTS: Hospital mortality was 1.8% (EF < or = 0.30, 3.6%; EF > 0.30, 1.4%; p = 0.002). Off-pump CABG did not have an impact on operative mortality (on-pump, 4%; off-pump, 3%; p = 0.509). Ejection fraction of 0.30 or less was not an independent risk factor of hospital mortality but predicted respiratory failure (odds ratio [OR] = 2.3) and sepsis (OR, 1.4). Long-term survival was significantly decreased in patients with EF of 0.30 or less: 1-year and 5-year survival 88% +/- 1.5% and 75% +/- 2.2% versus 96% +/- 0.4% and 81% +/- 1.2%, respectively (p = 0.001). Reoperation (OR, 6.9), peripheral vascular disease (OR, 3.2), chronic obstructive pulmonary disease (OR, 3.0), congestive heart failure (OR, 2.7), and female sex (OR, 2.1) were independent predictors of long-term survival. CONCLUSIONS: Excellent results after CABG can be expected in patients with EF of 0.30 or less, with minimal increase in mortality and acceptable postoperative morbidity. Long-term survival remains limited, but recent results are substantially better than historical reports. Careful preoperative patient selection and perioperative management are essential in these patients undergoing CABG. PMID- 17720382 TI - Invited commentary. PMID- 17720381 TI - Influence of pleurotomy on pulmonary function after off-pump coronary artery bypass grafting. AB - BACKGROUND: This study evaluated the influence of pleurotomy on pulmonary function after off-pump coronary artery bypass grafting (CABG) using the left internal thoracic artery (LITA). METHODS: Thirty patients were prospectively allocated into two groups: 15 patients with an opened left pleural cavity (OP group) and 15 patients with an intact pleural cavity (IP group). Bedside pulmonary function tests were recorded preoperatively and on postoperative days 1, 3, and 5. Arterial blood gas analyses and ratio of partial pressure of arterial oxygen (PaO2/fraction of inspired oxygen (FiO2) ratio were evaluated preoperatively and on postoperative day 1. RESULTS: A significant decrease of pulmonary function was observed in both groups until postoperative day 5. When compared with the percentage of the preoperative value, the forced vital capacity was significantly lower in the OP group than in the IP group on postoperative days 1 (33.3% +/- 8.3% versus 49.1% +/- 8.4%, p < 0.001), 3 (45.4% +/- 7.0% versus 62.1% +/- 8.6%, p < 0.001), and 5 (56.1% +/- 8.7% versus 77.5% +/- 11.6%, p < 0.001). Similar results were found for forced expiratory volume in 1 second on postoperative days 1 (35.7% +/- 8.6% versus 50.0% +/- 9.8%, p < 0.001), 3 (48.4% +/- 7.0% versus 61.5% +/- 9.02%, p < 0.001) and 5 (58.8% +/- 8.5% versus 75.9% +/- 10.2%, p < 0.001). The PaO2 value and the PaO2/FiO2 ratio dropped on postoperative day 1 in both groups (p < 0.05), with a higher fall in the OP group (p < 0.05). Orotracheal intubation time (p = 0.012) and hospital stay (p = 0.002) were lower in the IP group. CONCLUSIONS: Off-pump CABG using the LITA, independently of pleural opening, induced a significant reduction in early postoperative pulmonary function. However, the patients undergoing pleurotomy demonstrated more pronounced pulmonary dysfunction. PMID- 17720383 TI - Systemic inflammation after on-pump and off-pump coronary bypass surgery: a one month follow-up. AB - BACKGROUND: This study sought to assess inflammation activation in the follow-up (up to one month) of coronary bypass surgery performed both on- (CABG) and off pump (OPCAB). METHODS: Thirty patients, candidates for coronary surgery, were randomized to undergo CABG (n = 16) or OPCAB (n = 14). Blood samples were collected before the intervention, after protamine administration, and 4, 8, and 30 days after surgery. RESULTS: Plasma tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels significantly increased with respect to baseline from protamine administration up to eight postoperative days, whereas high sensitivity C-reactive protein (hs-CRP) and fibrinogen increased after surgery up to eight postoperative days in both groups. On the other hand, neutrophil elastase levels were higher than baseline from protamine administration up to four postoperative days in CABG, and at the time point eight days after surgery in OPCAB. The only significant differences between CABG and OPCAB in inflammatory markers occurred intraoperatively, after protamine administration, when TNF-alpha and elastase levels were higher in CABG, whereas no differences were detected between CABG and OPCAB at any postoperative time point. Postoperative increases in fibrinogen and hs-CRP were positively correlated with increases in IL-6, but not with postoperative changes in TNF-alpha both in CABG and OPCAB. CONCLUSIONS: After coronary bypass surgery, there is a protracted postoperative activation of inflammation persisting several days after surgery; this postoperative activation is not affected by the surgical strategy (on-pump or off-pump). PMID- 17720384 TI - Simple index to predict likelihood of skilled nursing facility admission after coronary artery bypass grafting among older patients. AB - BACKGROUND: Acceptable short-term mortality rates for elderly patients undergoing coronary artery bypass grafting (CABG) are reported in the literature. However, rather than death, older patients considering CABG are generally most concerned about a postoperative loss of functional independence. To address this concern, we describe an index that predicts a patient's likelihood of admission to a skilled nursing facility (SNF) after CABG. METHODS: Logistic regression analysis of the California hospital discharge database during a 5-year period was performed to identify the most prevalent preoperative International Classification of Disease, 9th Revision Clinical Modification (ICD-9-CM) diagnoses associated with SNF admission after primary CABG in patients aged 65 years or older. Each diagnosis was weighted according to odds ratios to develop an index that predicts the likelihood of discharge to a SNF. The index was validated using our institutional database. RESULTS: A total of 26,040 patients (mean age, 74.2 years; 67.2% men) fit our criteria. They had an in-hospital mortality rate of 3.09% and a 17.3% SNF discharge rate. Our index was a summation of nine selected preoperative ICD-9-CM diagnoses, which were assigned a value of 1 point (osteoarthritis, congestive heart failure, atrial fibrillation, myocardial infarction, anemia, obesity) or 2 points (female, chronic obstructive pulmonary disease, renal failure). Validation analysis produced a C statistic and pseudo r2 value of 0.6435 and 0.0408, respectively. Cut-point analysis suggests that patients with scores of 3 or higher can be considered "high-risk." CONCLUSIONS: We describe a simple index to identify older patients at low-risk and high-risk for SNF admission after CABG. Such tools may be useful in counseling older patients considering CABG. PMID- 17720385 TI - Off-pump coronary artery bypass with bivalirudin for patients with heparin induced thrombocytopenia or antiplatelet factor four/heparin antibodies. AB - BACKGROUND: This study assessed the use of bivalirudin as an alternative anticoagulant in patients with heparin-induced thrombocytopenia-thrombotic syndrome (HIT/TS) or antiplatelet factor four-heparin (anti-PF4/H) antibodies undergoing off-pump coronary artery bypass (OPCAB). METHODS: In a prospective, open-label, multicenter study, fifty-one patients with documented anti-PF4/H antibodies and (or) HIT/TS underwent OPCAB with bivalirudin anticoagulation (0.75 mg/kg i.v. bolus, 1.75 mg/kg/hour infusion). Procedural success (absence of death, Q-wave myocardial infarction, repeat revascularization, and stroke), bleeding, and transfusion at day seven/discharge, thirty days, and twelve weeks were assessed. RESULTS: Thirty-five patients (67%) were included with positive anti-PF4/H antibodies and no thrombocytopenia or thrombosis, eleven patients (22%) had thrombocytopenia, and five patients had clinical HIT/TS (10%). Procedural success at seven days/discharge was achieved in forty-seven patients (92%), while procedural success at thirty days and twelve weeks was 88%. There were no deaths. Chest tube output over the first twenty-four hours was 936 +/- 525 mL and twenty-five patients received a red blood cell transfusion during their hospitalization. Two patients required reexploration for persistent postoperative hemorrhage. CONCLUSIONS: Bivalirudin was an effective alternative anticoagulant for patients with HIT/TS or circulating anti-PF4/H antibodies undergoing OPCAB, with high rates of procedural success and an acceptable incidence of bleeding or transfusions. PMID- 17720386 TI - Invited commentary. PMID- 17720387 TI - Heparin-induced thrombocytopenia in left ventricular assist device bridge-to transplant patients. AB - BACKGROUND: The presence of heparin-induced thrombocytopenia (HIT) increases the risk for thromboembolic events in ventricular assist device (VAD) patients undergoing transplantation. However, cardiopulmonary bypass with alternative anticoagulants is often complicated by bleeding. Owing to this concern, we compared outcomes of HIT-positive versus control bridge-to-transplantation VAD patients; both groups were reexposed to heparin for cardiopulmonary bypass during transplant. METHODS: From February 2000 to January 2006, data were reviewed on 92 consecutive adult patients who underwent VAD placement as a bridge to transplantation. Patients in whom thrombocytopenia developed after heparin exposure were tested for HIT with an enzyme-linked immunosorbent assay for antiheparin/platelet factor-4 (HPF4) antibody (GTI Diagnostics, Waukesha, Wisconsin). During VAD support, heparin was avoided in HIT-positive patients, but all patients were reexposed to heparin during transplantation. Comparisons between HIT-positive and control patients for survival and freedom from thromboembolic events were determined using the Kaplan-Meier method and log-rank test. Continuous and categorical variables were compared using the Wilcoxon rank sum and Student t test. RESULTS: Twenty-four of the 92 patients (26.1%) were determined to be HIT positive by enzyme-linked immunosorbent assay. Survival to transplant was not different between the two groups. When compared with control patients, HIT-positive patients who were reexposed to heparin had a greater decrease in platelet counts immediately after transplant (postoperative days 1 to 4, p < 0.05). Despite this transient thrombocytopenia, there was no difference in posttransplant mortality or thromboembolism. CONCLUSIONS: Heparin-induced thrombocytopenia-positive VAD patients did not experience increased thromboembolism or mortality after heparin reexposure. In light of the risks of using heparin alternatives, heparin reexposure is a safe management strategy for HIT-positive VAD patients. PMID- 17720388 TI - Effects of pH management during selective antegrade cerebral perfusion on cerebral microcirculation and metabolism: alpha-stat versus pH-stat. AB - BACKGROUND: Selective cerebral perfusion (SCP) is used for extending the period during which surgical procedures can be safely performed. We sought to determine the direct effects of pH management on cerebral microcirculation and metabolism during SCP. METHODS: An experimental SCP porcine model was created by selectively allowing cold perfusate only into the bicarotid brachiocephalic trunk during the SCP period. Twenty-four piglets (6 to 8 weeks; mean weight, 26.1 +/- 4.1 kg) underwent 15-minute normothermic cardiopulmonary bypass, 45-minute cooling cardiopulmonary bypass, 60-minute SCP at 25 degrees C, and 45-minute rewarming cardiopulmonary bypass with either alpha-stat or pH-stat perfusion strategy randomly assigned. A cranial window was created over the parietal cortex for visualization of the cerebral vessels with intravital microscopy. Rhodamine stained leukocytes were observed in cerebral postcapillary venules for adhesion and rolling. Microdialysis analysis was used for determination of brain metabolism. RESULTS: Brain concentration of lactate was significantly higher in the alpha-stat group at 45 minutes of SCP, and at 15- and 45-minute rewarming intervals (p = 0.03; p = 0.003; and p = 0.05; respectively), reaching borderline statistical significance when assessed throughout the experiment (p = 0.06 for differences between groups). Further, at the end of cooling, the oxygen delivery tended to be higher in the pH-stat group (p = 0.07), whereas at the 30-minute rewarming interval, the oxygen extraction tended to be higher in the alpha-stat group (p = 0.06). There were no statistically significant differences between the groups in leukocyte-endothelial interaction, arterial diameter, or tissue oxygenation. CONCLUSIONS: The higher concentration of brain lactate and the tendency to higher oxygen extraction levels during rewarming with alpha-stat strategy suggests anaerobic metabolism occurred during SCP. No major differences between pH management strategies in cerebral microcirculation could be shown during SCP. PMID- 17720389 TI - Invited commentary. PMID- 17720390 TI - Maintenance of myocyte volume homeostasis during stress by diazoxide is cardioprotective. AB - BACKGROUND: We previously demonstrated that myocyte swelling and reduced contractility secondary to hyperkalemic cardioplegia and hyposmotic stress are attenuated by the addition of diazoxide, an adenosine triphosphate-sensitive potassium channel (K(ATP)) opener. The goal of this study was to investigate the effect of diazoxide on myocyte swelling and reduced contractility after metabolic inhibition and to attempt to summarize the potential mechanisms involved. METHODS: Isolated rabbit myocytes were perfused with Tyrode's control solution for 20 minutes, followed by test solution for 20 minutes. Test solutions included (1) Tyrode's control, (2) a metabolic inhibition solution containing sodium cyanide and 2-deoxyglucose, (3) metabolic inhibition plus diazoxide, (4) metabolic inhibition plus diazoxide plus HMR1098 (a sarcolemmal K(ATP)-channel blocker), or (5) metabolic inhibition plus diazoxide plus 5-hydroxydeconoate (a mitochondrial K(ATP)-channel blocker). Myocytes were then reexposed to Tyrode's solution for 20 minutes. Volume measurements were taken every 5 minutes. Contractility was recorded using edge-detection software at baseline and at 10 and 20 minutes of reexposure to Tyrode's solution. RESULTS: Simulated ischemia (metabolic inhibition) caused significant myocyte swelling and associated reduced contractility. The addition of diazoxide abolished myocyte swelling and attenuated the associated reduced contractility. Observations with diazoxide were unchanged by the addition of HMR 1098 or 5-hydroxydeconoate. CONCLUSIONS: Diazoxide, with or without either K(ATP)-channel blocker, attenuated the significant myocyte swelling and reduced contractility secondary to metabolic inhibition. These data suggest a role for diazoxide, independent of the K(ATP) channel, in myocyte volume homeostasis. In addition, the prevention of myocyte swelling resulted in improved contractility, consistent with previous data and the hypothesis that myocyte swelling may participate in the phenomenon of myocardial stunning. PMID- 17720391 TI - Invited commentary. PMID- 17720393 TI - Current risk factors and outcomes for the arterial switch operation. AB - BACKGROUND: The arterial switch operation is the preferred treatment for dextrotransposition of the great arteries and some forms of double-outlet right ventricle. METHODS: All patients undergoing an arterial switch operation at a single institution from January 1, 1999, to September 1, 2005, were reviewed. RESULTS: Of the 168 patients, median age was 2 days (range, 0 to 358) and weight was 3.5 kg (range, 1.9 to 11.8 kg). Eleven patients were less than 36 weeks gestational age. Forty percent had coronary patterns other than usual. Mean cardiopulmonary bypass (CPB) time was 147 +/- 45 minutes, and mean cross-clamp time was 77 +/- 27 minutes. At a mean follow-up of 19 +/- 21 months, there were 10 (6%) hospital and 4 (3%) late deaths. Actuarial 1-month, 1-year, and 3-year survivals were 94%, 90%, and 89%, respectively. Bivariate analysis revealed weight less than 2.5 kg (p = 0.032), gestational age less than 36 weeks (p = 0.002), and CPB time greater than 150 minutes (p = 0.0075) decreased hospital survival. Intermediate-term survival was negatively impacted by weight less than 2.5 kg (p = 0.017), gestational age less than 36 weeks (p = 0.0096), CPB time greater than 150 minutes (p = 0.0050), and age at presentation greater than 4 weeks (p = 0.034). By multivariate analysis, gestational age less than 36 weeks (p = 0.0051) and CPB time greater than 150 minutes (p = 0.016) were independent risk factors for hospital mortality. Gestational age less than 36 weeks (p = 0.0096) and CPB time greater than 150 minutes (p = 0.005) were also independent predictors of intermediate-term mortality. Coronary anatomy could not be shown to affect survival, including no deaths among the 12 patients with intramural coronaries. CONCLUSIONS: The arterial switch operation can be performed with low mortality regardless of diagnosis or coronary pattern. The premature patient and minimizing CPB time remain as challenges to optimize outcomes for the arterial switch operation. PMID- 17720392 TI - Bioabsorbable gelatin sheets latticed with polyglycolic acid can eliminate pericardial adhesion. AB - BACKGROUND: As an extension of our previous studies on bioabsorbable pericardial substitutes, we have created a new form of gelatin sheets latticed with bioabsorbable polyglycolic acid (PGA). This study was undertaken to evaluate the biomechanical property of the sheet and the preventive effect on pericardial adhesions after pericardial replacement in a canine model before its clinical applications. METHODS: The mechanical property was assessed by measuring tension of suture pull-out at first break test. Fifteen dogs underwent partial pericardial replacement with the bioabsorbable sheets through a left thoracotomy. Macroscopic assessment for severity of adhesions and microscopic evaluation for histologic changes were made at 2, 4, 12, and 24 weeks postoperatively. RESULTS: The latticed sheets exhibited tenfold higher tension of disruption at the suturing margin compared to our previously developed gelatin sheets (619 +/- 141 versus 62 +/- 7 gf, p < 0.001), and demonstrated equivalent strength to that of clinically available expanded polytetrafluoroethylene membrane. During rethoracotomy, adhesions between the epicardium and the pericardial substitutes were moderate at the 4-week interval and resolved completely after 12 weeks postoperatively. Inflammatory reaction scores graded into 4 scales on histologic assessment were 2 +/- 0.0, 1.6 +/- 0.6, and 0.3 +/- 0.5 at 4, 12, and 24 weeks, respectively. Inflammatory reaction significantly decreased from the 4-week interval to the 24-week interval after the pericardial replacement (p < 0.05). CONCLUSIONS: The bioabsorbable gelatin sheets latticed with PGA gained improved mechanical properties compared with the previously reported gelatin sheets without impairing its bioabsorbability. The bioabsorbable sheet could eliminate pericardial adhesions after being replaced with regenerated tissue. PMID- 17720394 TI - Outcome after Fontan failure and takedown to an intermediate palliative circulation. AB - BACKGROUND: Fontan takedown to an intermediate palliative circulation is an important treatment option for patients with acute or subacute failure of a Fontan circulation from a variety of causes. Little is known about the subsequent outcome of these patients or their potential candidacy for a second attempt at Fontan completion. METHODS: Patients followed up at Children's Hospital Boston who underwent takedown of a Fontan circulation to an intermediate palliative circulation within 1 year of Fontan completion were reviewed. RESULTS: Between 1979 and 2006, 53 patients underwent Fontan takedown at a median age of 2.3 years (range, 0.3 to 36.5 years). Takedown was performed during the Fontan procedure itself in 12 patients (22%), within the first postoperative month in 31(58%), and between 1 month and 1 year in 10 (18%). Overall, 29 patients (55%) survived the early period after takedown, and 19 ultimately underwent successful Fontan completion a median of 4.6 years after takedown; all but one was alive a median of 6.4 years later. Thirteen (68%) of the 19 had treatable abnormalities contributing to Fontan failure. CONCLUSIONS: Fontan takedown can provide effective stabilization of the acutely or subacutely failing Fontan circulation, although a substantial number of patients die early despite Fontan takedown. Subjects surviving the perioperative period can often undergo uneventful redo Fontan. A thorough evaluation for treatable abnormalities should be performed in all patients with a failing Fontan circulation and in patients who undergo Fontan takedown. PMID- 17720395 TI - Persistent antegrade pulmonary blood flow post-glenn does not alter early post Fontan outcomes in single-ventricle patients. AB - BACKGROUND: The bidirectional Glenn cavopulmonary anastomosis (BDG) represents the standard interim procedure in treatment of patients with single-ventricle physiology. Anterograde pulmonary blood flow (APBF) maintained after BDG has been shown both to improve and to complicate postoperative clinical course. We studied its effects on outcome after BDG and eventual Fontan completion. METHODS: From November 1995 to November 2005, 60 patients underwent BDG and Fontan. All patients had APBF from the ventricle to the pulmonary artery at time of BDG. In group 1 (n = 39) APBF was maintained after BDG, whereas APBF was interrupted at BDG in group 2 (n = 21). Cardiac catheterization data, interstage morbidity, and postoperative outcome variables were recorded. RESULTS: Pre-BDG hemodynamics differed only in that the mean pulmonary artery pressure was higher in group 2 (17.0 +/- 4.4 mm Hg) than in group 1 (13.8 +/- 4.5 mm Hg; p = 0.03). There were no differences between groups 1 and 2 in BDG outcome variables. At pre-Fontan catheterization, group 1 had higher mean pulmonary artery pressure (13.3 versus 10.9 mm Hg, p = 0.01), arterial oxygen saturation (85.8 versus 80.9%, p = 0.0001), and fewer collateral vessels were coil embolized than in group 2 (0.9 versus 1.6, p = 0.02). Mean ventricular end-diastolic pressure was similar between groups. The Nakata index in group 1 remained stable from pre-BDG to pre Fontan (348 versus 391, p = 0.24), but it decreased in group 2 (375 versus 227, p = 0.046). CONCLUSIONS: Patients with anterograde pulmonary blood flow after BDG had a modest increase in pulmonary artery growth and arterial oxygen saturations, and decreased collateral vessel formation. This did not, however, confer additional benefit on outcome after BDG or on eventual Fontan completion. PMID- 17720396 TI - Nonfenestrated extracardiac total cavopulmonary connection in 132 consecutive patients. AB - BACKGROUND: The study was conducted to assess the need for fenestration for completion of a total cavopulmonary connection (TCPC) with the most recent modification of an extracardiac conduit. METHODS: The extracardiac approach was introduced to our institution in January 1999. Between June 2000 and June 2006, 132 consecutive patients were treated without a fenestration. At the time of TCPC, the median age was 31 months (range, 16 251), with 93 patients (70%) being younger than 48 months. Median patient weight was 12.5 kg (range, 9 to 66 kg). A previous partial cavopulmonary connection (PCPC) was accomplished in 117 patients (88.6%), without additional pulmonary blood flow. RESULTS: Thirty-day-mortality was 1.5%. Median time to extubation was 14 hours (range, 3 hours to 126 days). Initial pulmonary artery pressure value was 16.5 +/- 2.2 mm Hg, and 13.1 +/- 1.8 after extubation. Median drainage requirement was 4 days (range, 1 to 45), and median duration of hospitalization was 20 days (range, 5 to 128). Thirty-one (24%) required repeat drainage insertion. No subsequent fenestration was performed, and at hospital discharge no significant repeat effusions were observed. Multiple covariate logistic regression revealed longer time interval from PCPC to extracardiac TCPC (p = 0.006) as a significant predictor of pleural drainage lasting longer than 4 days, and older age at the time of extracardiac TCPC (p = 0.040) as a risk factor for hospitalization more than 20 days. Higher pulmonary artery pressure 3 hours postoperatively was a significant predictor for both outcome variables in the multivariate model (p = 0.013, p = 0.001). CONCLUSIONS: In general, an extracardiac TCPC can be performed without fenestration. Early staging of patients with functional single ventricle physiology may be one of the keys for these findings. PMID- 17720397 TI - Prevalence and associated risk factors for intervention in 313 children with subaortic stenosis. AB - BACKGROUND: We sought to determine the prevalence of intervention and associated factors in children presenting with subaortic stenosis. We also investigated whether a protocol adopted in 1994 of early subaortic resection at a preoperative mean systolic gradient across the left ventricular outflow tract (LV gradient) greater than 30 mm Hg was supported by longitudinal outcomes. METHODS: Record review of all children (n = 313) diagnosed with subaortic stenosis was conducted between 1975 and 1998 at our institution. Cox proportional hazard models determined the prevalence and associated factors for initial subaortic resection. Mixed models of serially obtained echocardiographic data (n = 933) established longitudinal LV gradient trends and identified factors associated with more rapid LV gradient progression. RESULTS: Median age at presentation was 8 months. Freedom from initial subaortic resection was 40% at 16 years from diagnosis. Earlier progression to subaortic resection was associated with patient characteristics at presentation, including a higher initial LV gradient (p < 0.001), larger aortic annulus z-score (p = 0.005), smaller body surface area (p < 0.001), and smaller mitral annulus z-score (p = 0.003). Initial resection was also associated with a faster rate of LV gradient progression (p = 0.003). Factors determining the increased rate of LV gradient progression included an initial LV gradient greater than 30 mm Hg (p < 0.001), initial aortic valve thickening (p = 0.003), and attachment of subaortic stenosis to the mitral valve (p = 0.003). Worse aortic regurgitation grade with time was also associated with an initial LV gradient greater than 30 mm Hg (p < 0.001). CONCLUSIONS: Subaortic resection should be delayed until the LV gradient exceeds 30 mm Hg because most children with an initial LV gradient less than 30 mm Hg have quiescent disease. PMID- 17720398 TI - Right ventricle-to-pulmonary artery conduit longevity: is it related to allograft size? AB - BACKGROUND: Cryopreserved valved allografts are routinely oversized to account for somatic growth in children requiring right ventricle-to-pulmonary artery (RV PA) continuity. The objective of this study is to determine the effect of oversizing on conduit longevity. METHODS: We reviewed the records of all patients undergoing RV-PA cryopreserved valved allograft placement from 1988 to 2006 for diagnosis, age, allograft type, time to valved conduit explant, and indication for surgery. Conduit size at the time of insertion was compared with pulmonary valve size normalized for body surface area (z score). Multivariate Cox regression models with cluster analysis were constructed to assess risk of allograft oversizing for conduit failure. Kaplan-Meier analysis was used to obtain median freedom from explantation time. RESULTS: A total of 140 cryopreserved valved allografts (z score, 1.8 +/- 1.3; range, -1.5 to 4.9) were implanted in 99 patients (median age, 5.6 years). Reoperation was required in 66 (67%) of 99 patients during the study period. Modeling z scores as a dichotomous variable revealed that risk of allograft explantation increases 113% when allografts with z scores of 2.7 or higher are used compared with those with z scores of less than 2.7 (p < 0.01). Median adjusted freedom from explantation for this same grouping was 4.9 years versus 9.4 years. The presence of branch pulmonary artery stenosis shortens the conduit life (p < 0.001), whereas insertion of a pulmonary allograft may extend the conduit life (p = 0.13). CONCLUSIONS: Cryopreserved valved allograft oversizing (z score > or = 2.7) in the pulmonary position results in decreased longevity in children. Presence of branch pulmonary artery stenosis is also associated with earlier conduit explantation. PMID- 17720399 TI - Autologous right atrial wall patch for closure of atrial septal defects. AB - BACKGROUND: We used the right atrial free wall as a patch to close atrial septal defects (ASD) and report its results. METHODS: Between July 1998 and April 2006, 87 patients (mean age, 21.9 +/- 13.9 years; range, 7 months to 54 years), underwent closure of ASD with an autologous right atrial free wall patch. The underlying diagnosis were very large secundum ASD in 51 patients, sinus venosus defect in 15, primum ASD in 5, large defect resulting from excision of a left atrial myxoma in 12, complete atrioventricular canal defect in 1, total anomalous pulmonary venous return with ASD in 2, and Ebstein anomaly with a large ASD in 1. Associated surgical procedures were mitral valve repair in 18 patients, repair of total or partial anomalous pulmonary venous drainage in 17, mitral valve replacement in 1, and tricuspid valve repair for Ebstein anomaly in 1. RESULTS: There were two early deaths. One patient with primum defect and preoperative congestive heart failure died 3 weeks postoperatively from refractory ventricular fibrillation. Another patient died from persistent congestive heart failure after undergoing reoperation for residual mitral regurgitation. The remaining patients were discharged after 4 to 9 days. No flow was detected across the septal patch on predischarge echocardiography. At a mean follow up of 53.4 +/- 26.7 months (range, 1 to 103 months), all patients except 1 are in sinus rhythm. One patient underwent reoperation for failed mitral valve repair after 1 month. At reoperation, the patch was intact with normal texture and without any suture dehiscence. Histopathologic examination of the explanted patch revealed viable endothelium and subendothelial muscle on both the surfaces of the patch. Results of Holter monitoring in 9 patients were normal. Electrophysiologic studies in 2 patients recorded normal atrial potentials from the site of the patch. No patch shrinkage, calcification, or thromboembolic complications were noted. CONCLUSIONS: The autologous, free, right atrial wall can be safely used as a patch for ASD closure and offers several advantages. PMID- 17720400 TI - Role of nitric oxide pathway in placental dysfunction following fetal bypass. AB - BACKGROUND: The etiology of placental dysfunction after fetal cardiopulmonary bypass remains unknown. The placental nitric oxide (NO) pathway has been implicated in this pathophysiology. We set out to examine possible perturbations in this pathway in an ovine model of fetal bypass. METHODS: Ovine fetuses (n = 14) between 100 and 114 days of gestation, instrumented to measure hemodynamics and umbilical blood flow, were placed on bypass for 30 minutes and followed after bypass for 2 hours. Sham controls (n = 6) were instrumented but did not undergo bypass. Real-time, in-vivo NO concentrations were measured in the placental circulation. To examine other components of the NO pathway, fetal plasma samples were analyzed by immunoassays for total NO metabolite and cyclic guanosine 3',5' cyclic monophosphate (cGMP) levels. In addition, the expression of phosphodiesterase-5 was examined in placenta by immunohistochemistry. Statistical analysis was performed using analysis of variance with least significant difference post hoc tests (p < or = 0.05). RESULTS: With the onset of bypass, an immediate increase occurs in umbilical NO concentrations. These return to baseline with cessation of bypass, and decline thereafter. In contrast, there was a linear increase in fetal plasma cGMP levels and a decline in NO metabolite concentrations through the post-bypass period. There was a dramatic increase in placental phosphodiesterase-5 expression with 30 minutes of bypass. The changes occur simultaneously with decreasing umbilical flows, increased placental vascular resistance, and worsening placental gas exchange. CONCLUSIONS: Fetal bypass leads to significant reductions in placental NO concentrations despite increases in fetal plasma cGMP and placental phosphodiesterase-5 levels, indicative of perturbations in the fetal-placental NO pathway. PMID- 17720401 TI - Anatomic segmentectomy in the treatment of stage I non-small cell lung cancer. AB - BACKGROUND: Segmentectomy for early-stage non-small cell lung cancer (NSCLC) remains controversial and has been previously associated with high local recurrence rates. We compared the outcomes of anatomic segmentectomy with lobectomy for stage I NSCLC and investigated the impact of surgical resection margins on recurrence. METHODS: From 2002 to 2006, 182 anatomic segmentectomies (114 open, 68 video-assisted thoracic surgery [VATS]), were performed for stage 1A (n = 109) or IB (n = 73) NSCLC. These were compared with 246 lobectomies (1A, 114; 1B, 132). Variables analyzed included hospital course, mortality, and patterns of recurrence and survival. RESULTS: All segmentectomy surgical margins were free of tumor (average margin, 18.2 mm). Operative time (147 versus 216 minutes; p < 0.0001) and estimated blood loss (185 versus 291 mL; p = 0.0003) were significantly reduced after segmentectomy compared with lobectomy. Thirty day mortality (1.1% versus 3.3%), total complications, disease-free recurrence, and survival were similar between segmentectomy and lobectomy at a mean follow-up of 18.1 and 28.5 months, respectively. There were 32 recurrences after segmentectomy (17.6%) at a mean of 14.3 months (14 locoregional [7.7%], 18 distant [9.9%]), and 89% of recurrences were seen when tumor margins were 2 cm or less. Margin/tumor diameter ratios exceeding 1 were associated with a significant reduction in recurrence rates compared with ratios of less than 1 (25.0% versus 6.2%; p = 0.0014). CONCLUSIONS: Anatomic segmentectomy can be performed safely by an open or VATS approach. Segmentectomy outcomes compare favorably with standard lobectomy for stage I NSCLC. Margin/tumor ratios of less than 1 are associated with a higher rate of recurrence. Lobectomy should be considered as primary therapy when such margins are not obtainable with segmentectomy in the good-risk patient. PMID- 17720402 TI - Prognostic factors in resected satellite-nodule T4 non-small cell lung cancer. AB - BACKGROUND: The 1997 non-small cell lung cancer staging revisions assigned a T4 descriptor to satellite nodules in the primary tumor lobe. We reviewed our experience of satellite-nodule T4 non-small cell lung cancer following these revisions and evaluated prognostic factors for this group. METHODS: All patients who underwent resection of non-small cell lung cancer between April 1997 and June 2005 with satellite nodule(s) confirmed at pathologic examination were identified from our institutional Lung Tumor Registry. Case notes and pathology reports were reviewed and data collected on possible prognostic factors. Survival was modeled using the Kaplan-Meier method, and survival differences between groups were analyzed using the log-rank test. RESULTS: From 1,276 non-small cell lung cancer patients who underwent resection, 137 were staged pT4, and 35 were T4-satellite nodules. Median follow-up was 25 months (range, 1 to 102 months). Median main tumor size was 3.0 cm (range, 1 to 9.8 cm). Adenocarcinoma or bronchioloalveolar carcinoma was the predominant histologic diagnosis (n = 28; 80%). One-, 3- and 5 year survival was 86%, 69%, and 57%, respectively; median survival was 68 months. During the same period, 137 patients undergoing resection for all T4 lesions had a 1-, 3-, and 5-year survival of 68%, 53%, and 18%, respectively. Adenocarcinoma or bronchioloalveolar carcinoma histologic diagnosis (adenocarcinoma or bronchioloalveolar carcinoma versus squamous, 75% versus 67% 3-year survival; p = 0.0026), female gender (66% versus 49% for males, 5-year survival; p = 0.041), and absence of vascular invasion (no invasion versus vascular invasion, 74% versus 20% 5-year survival; p = 0.0101) were significant predictors of better survival. CONCLUSIONS: Survival for resected T4 non-small cell lung cancer with satellite nodule(s) in the primary lobe is better than for other T4 lesions, and the T4 descriptor may unduly upstage these cases. The current T4 descriptor represents a heterogeneous population. PMID- 17720403 TI - Accessing the aortopulmonary window (#5) and the paraaortic (#6) lymph nodes in patients with non-small cell lung cancer. AB - BACKGROUND: The purpose of this study was to assess the efficacy of the different techniques of lymph node biopsies in patients with suspected metastatic non-small cell lung cancer (NSCLC) in the subaortic (station #5) and paraaortic (station #6) lymph nodes. METHODS: This was a retrospective cohort study conducted of a prospective database of patients between January 2003 and June 2006 with suspected N2 disease only in the #5 or #6 lymph nodes, or both. All patients had integrated 2-deoxy-2-fluoro-D-glucose positron emission tomography/computed tomography, and nodal biopsy or thoracotomy, or both, with complete thoracic lymphadenectomy. RESULTS: There were 112 patients with clinically suspected N2 disease in lymph node stations #5 or #6, or both. The primary tumor was in the left upper lobe in 98 (88%) and in the left lower lobe in 14 (13%), and 58 had pathologic N2 disease in #5 or #6 lymph node stations only. Mediastinoscopy, used in all patients found, unsuspected N3 disease in 4 patients (3.6%) and N2 (#4L) disease in 12 (11%). Endoscopic ultrasound with fine needle aspiration (EUS-FNA), implemented in 62 patients (56%), correctly identified 41 patients (66%). Left single-incision video-assisted thoracic surgery (VATS) was used in 39 patients and was correct in 100%. Of the 58 patients, 53 (91%) completed neoadjuvant chemoradiotherapy, followed by resection, and their 5-year survival was 64%. CONCLUSIONS: EUS-FNA is less accurate for the #5 and #6 lymph node stations than left VATS. We prefer left VATS over the Chamberlain procedure for patients with suspected nodal metastases isolated only to #5 or #6 stations, and if positive, we prefer neoadjuvant therapy. The advantage of neoadjuvant therapy followed by resection compared with resection followed by adjuvant therapy remains controversial; and hence, the role for biopsy of these nodes is also controversial. PMID- 17720404 TI - Association of chronic obstructive pulmonary disease and tumor recurrence in patients with stage IA lung cancer after complete resection. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) poses a high risk for postoperative pulmonary complications after lung cancer surgery. We sought to determine the impact of this disease on long-term survival after surgical resection and to identify prognostic factors in pathological stage IA lung cancer. METHODS: A retrospective chart review was completed in 442 patients with pathological stage IA lung cancer, who had a lobectomy with systematic lymph node dissection (30.3%), out of 1,461 patients who underwent lung cancer surgery at our hospital from January 1990 to April 2005. The functional definition of COPD, according to the spirometric guidelines of the Global Initiative for Chronic Obstructive Lung Disease, was forced expiratory volume in 1 second to forced vital capacity less than 70% (FEV1/FVC). The postoperative complications were compared between the non-COPD (362 patients) and COPD (80 patients) groups. Overall survival and disease-free survival were analyzed using the Kaplan-Meier method and log-rank test. Prognostic factors were identified by univariate and multivariate analyses. RESULTS: The frequencies of all pulmonary complications except for pneumonia and tracheostomy were similar between the two groups. Overall survival and disease-free survival in the COPD group were significantly worse than those in the non-COPD group (p < 0.0001 and p = 0.037, respectively). Significant prognostic factors were larger tumor size (p = 0.0035) and COPD (p = 0.0147). Significant risk factors for cancer recurrence were larger tumor size (p = 0.001) and COPD (p = 0.0105) by multivariate analyses. CONCLUSIONS: Patients with COPD had poorer long-term survival. This may be due to a higher incidence of tumor recurrence. PMID- 17720405 TI - Invited commentary. PMID- 17720406 TI - The side of pneumonectomy influences long-term survival in stage I and II non small cell lung cancer. AB - BACKGROUND: The impact of pneumonectomy as an independent factor on long-term survival after lung resection for centrally or locally advanced non-small cell lung cancer (NSCLC) remains controversial. The aim of this paper is to study the impact of pneumonectomy, and the influence of side of surgery, on long-term survival in patients with pathologic stage I and II NSCLC. METHODS: A retrospective review of a prospective multi-institutional database of patients operated on for lung cancer was undertaken. In all, 1,475 patients with pathologic stage I or II NSCLC were studied (421 underwent pneumonectomy; 1,054 had a lobectomy/bilobectomy). Survival and impact of side of surgery for pneumonectomy and lesser resection groups were analyzed and compared using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: Median survival was worse after pneumonectomy than after less extensive resections for patients overall (33 versus 57 months) and for those with stage I NSCLC (38 versus 70 months); however, median survival was better after pneumonectomy for stage II left tumors (55 versus 19 months). Pneumonectomy was an independent adverse determinant of survival for both stage I right tumors (p < 0.001) and stage I left tumors (p < 0.001), but was associated with improved survival for stage II left tumors (p = 0.009). CONCLUSIONS: Pneumonectomy was found to be an independent determinant of survival in patients with stage I and II NSCLC, but results differed for right- and left-sided tumors. Further studies of survival comparing pneumonectomy with lesser resections should differentiate between right and left procedures. PMID- 17720407 TI - Invited commentary. PMID- 17720409 TI - Bronchial stump buttressing with an intercostal muscle flap in diabetic patients. AB - BACKGROUND: The development of a bronchopleural fistula (BPF) is a devastating complication after lung resection. Diabetic patients exhibit a high propensity for postpneumonectomy complications, particularly BPF. This study evaluated the use of an intercostal muscle flap to reinforce the bronchus in high-risk diabetic patients after pneumonectomy. METHODS: From February 2002 to December 2005, 70 patients with established diabetes mellitus undergoing pneumonectomy were prospectively enrolled in this study. Patients were randomized to have their bronchial stump reinforced with an intercostal muscle flap or to a conventional resection. A univariable statistical analysis was performed to assess differences in perioperative variables and in outcomes of interest. A multivariable logistic regression analysis was also performed to evaluate the association of BPF development with a number of confounding variables, including intercostal muscle flap usage. RESULTS: Randomization ensured that groups were equally distributed. Mean follow-up was 18 +/- 9.2 months. The group that received an intercostal muscle flap had a lower incidence of BPF development (0% versus 8.8%; p = 0.02) and of empyema (0% versus 7.4%; p = 0.05) compared with the group that received conventional pneumonectomy. CONCLUSIONS: The low incidence of BPF and empyema observed in patients who received an intercostal muscle flap suggest that bronchial stump reinforcement with this technique is a highly effective method for the prevention of BPF in high-risk diabetic patients. PMID- 17720408 TI - Role of positron emission tomography scanning in the management of lung nodules detected at baseline computed tomography screening. AB - BACKGROUND: Indeterminate noncalcified lung nodules are a frequent finding when low-dose computed tomography (LD-CT) is used for lung cancer screening. The best clinical management for such nodules remains uncertain. We present results using positron tomography scanning (CT-PET) to evaluate LD-CT-detected lung nodules during the first year of the Continuing Observation of Smoking Subjects (COSMOS) early detection trial for lung cancer. METHODS: A total of 5200 asymptomatic current or former smokers (> or = 20 pack-years) older than 50 years of age were enrolled in a single-institution screening trial using annual LD-CT. Growing nodules and those with a maximum diameter exceeding 8 mm were studied with CT PET. Transthoracic needle biopsy was not a routine part of the protocol. RESULTS: During the first year of study, 157 subjects underwent CT-PET, 66 of whom underwent surgical biopsy. Of the 58 lung cancers found on surgical biopsy, 51 were positive (standard uptake value > 2.0) and seven were negative for malignancy by CT-PET. Sensitivity was 88% overall, but 100% in the subgroup with solid nodules of 10 mm or more. Among the 8 patients with benign disease at surgical biopsy, CT-PET was positive in 6 and negative in 2. CONCLUSIONS: CT-PET is a highly promising modality for identifying potentially malignant lesions in screening-detected lung nodules and appears particularly useful as an alternative, in the screening setting, to invasive procedures for the further investigation of uncertain nodules. Our findings also indicate that the standard uptake value threshold for positivity should be lowered for small nodules (< 10 mm). Longer follow-up and larger prospective studies are necessary to confirm these preliminary findings. PMID- 17720410 TI - Invited commentary. PMID- 17720411 TI - Sarcomatoid carcinoma of the lung: a predictor of poor prognosis. AB - BACKGROUND: Sarcomatoid cancer (SARC) of the lung is a rare histologic type of non-small cell lung cancer (NSCLC). Although believed to be associated with poor prognosis, its effect on survival and recurrence has not been well defined. Our goal was to determine the prognostic significance of SARC histology in patients undergoing pulmonary resection. METHODS: We retrospectively evaluated all patients who underwent pulmonary resection for NSCLC during a 20-year period at the University of Texas MD Anderson Cancer Center and compared recurrence and survival rates of patients with SARC with a cohort of patients with typical NSCLC. To account for known prognostic factors such as smoking status, age, gender, pathologic stage, and adjuvant therapy, we used one-to-one matching based on propensity scores. RESULTS: The study included 63 SARC patients and 1133 NSCLC patients with complete data. Propensity score matching identified 63 NSCLC patients that were similar to the 63 SARC patients from known clinical factors. The 5-year survival for SARC patients was 24.5% compared with 46.3% for NSCLC patients (p = 0.01); median time to recurrence was 11.3 months and 61.4 months, respectively (p = 0.001). CONCLUSIONS: Compared with other histologic subtypes, SARC behaves in an aggressive fashion. These tumors are frequently symptomatic, are locally advanced, and have higher rates of recurrence. Future investigation of novel treatment approaches is warranted. Nonsurgical treatment modalities may be appropriate for patients with clinically advanced disease. PMID- 17720412 TI - Invited commentary. PMID- 17720414 TI - Invited commentary. PMID- 17720413 TI - Use of aprotinin in extrapleural pneumonectomy: effect on hemostasis and incidence of complications. AB - BACKGROUND: The purpose of this study was to examine the effect of aprotinin on blood loss in extrapleural pneumonectomy and to identify potential treatment related complications. METHODS: Between March 1, 1999, and July 1, 2004, 27 (52%) of 52 patients who underwent extrapleural pneumonectomy received half-dose aprotinin (1 million kallikrein inhibition units load; 250,000 kallikrein inhibition units per hour infusion). A retrospective data review and analysis were performed. RESULTS: The mean age was 59.8 +/- 11 years, and 45 of 52 patients (87%) were male. Indications for extrapleural pneumonectomy were malignant pleural mesothelioma (n = 50) and pleural-based sarcoma (n = 2). The administration of aprotinin had no significant effect on intraoperative blood loss (1,010 +/- 599 versus 1,182 +/- 688 mL; p = 0.34) or units of packed red blood cells transfused intraoperatively (2.0 +/- 1.7 versus 1.9 +/- 1.7 units; p = 0.86). None of the patients who received aprotinin required the use of non packed red blood cells blood products, but 4 patients (16%) who did not receive aprotinin required such transfusion (p < 0.05). Postoperative chest tube output at 12 and 24 hours was lower in the aprotinin group (381 +/- 195 and 867 +/- 313 mL, respectively) compared with the control group (725 +/- 527 and 1,221 +/- 442 mL, respectively; p < 0.03). There was no significant difference in incidence of postoperative thromboembolic events between the aprotinin and the control group (5 versus 4 patients; p = 1.0), and 2 patients in each group experienced renal insufficiency (p = 1.0). CONCLUSIONS: Half-dose aprotinin did not decrease intraoperative blood loss or packed red blood cells transfusion in extrapleural pneumonectomy. However, use of aprotinin was associated with decreased use of non packed red blood cells blood products and lower postoperative chest tube output. Aprotinin administration was not associated with an increase in incidence of postoperative complications. PMID- 17720415 TI - Seven-day artificial lung testing in an in-parallel configuration. AB - BACKGROUND: A thoracic artificial lung, the MC3 Biolung, is being developed as a bridge to lung transplantation or as a treatment for acute respiratory insufficiency. METHODS: The thoracic artificial lung was tested in 10 sheep with the goal of 7 days of respiratory support. The sheep were recovered from surgery and monitored awake for 7 days. Hemodynamics, blood gases, blood cell counts, and organ function were recorded, and after 7 days, all sheep were euthanized and necropsied. RESULTS: Seven sheep survived the full duration. Cardiac output and mean arterial blood pressure were unchanged, averaging 4.7 +/- 0.8 L/min and 98 +/- 10 mm Hg, respectively. Arterial oxygen tension and device oxygen transfer rate were also unchanged, averaging 110 +/- 26 mm Hg and 97.7 +/- 35 mL/min, respectively. Arterial carbon dioxide tension was within normal ranges during the entire experiment, averaging 37.4 +/- 3.8 mm Hg. Artificial lung blood flow decreased from 51% +/- 14% of cardiac output on day 1 to 30% +/- 16% by day 7 because of changes in natural and artificial lung resistance. White blood cell counts were significantly elevated on days 5 and 7, and lastly, kidney and liver function remained normal, although signs of kidney infarction or hemorrhage were noted. CONCLUSIONS: The thoracic artificial lung is suitable for 7-day attachment, but improvements in blood biocompatibility are warranted. PMID- 17720416 TI - Virtual mediastinoscopy for safer and more accurate mediastinal exploration. AB - PURPOSE: Virtual endoscopy can theoretically produce images of hollow organs from computed tomographic scanning by discriminating walls with the air space. We produced virtual images of the mediastinum (ie, virtual mediastinoscopy based on positron emission tomography and computed tomography scanning data to visualize lymph nodes and great vessels similar to cervical mediastinoscopy). DESCRIPTION: Virtual images from 5 patients with positive mediastinal positron emission tomography findings were produced using computer software designed for virtual endoscopy. Visualization of lymph nodes and vessels was done based on positron emission tomography-computed tomography and enhanced computed tomographic scanning data, respectively. EVALUATION: Virtual mediastinoscopy clearly showed three-dimensional relationships between active nodes and surrounding structures. Great vessels, such as the innominate artery and azygos vein, which require assessment during a mediastinoscopy, were visualized in virtual movies. Further, perspective views in the craniocaudal direction based on surgeon-orientation, simulated actual views were obtained during cervical video mediastinoscopy. CONCLUSIONS: Virtual mediastinoscopy provided realistic images of the mediastinal anatomy, and has the potential to make cervical mediastinoscopy and other mediastinal explorations safer, as well as more accurate. PMID- 17720417 TI - Invited commentary. PMID- 17720419 TI - Invited commentary. PMID- 17720418 TI - Correction of aortic insufficiency with an external adjustable prosthetic aortic ring. AB - PURPOSE: Less invasive, valve-sparing options are needed for patients with aortic insufficiency (AI). We sought to evaluate the feasibility of reducing AI with an external adjustable aortic ring in an ovine model. DESCRIPTION: To create AI, five sheep underwent patch plasty enlargement of the aortic annulus and root by placement of a 10 x 15 mm pericardial patch between the right and noncoronary cusps. An adjustable external ring composed of a nylon band was fabricated and placed around the aortic root. EVALUATION: Aortic flow, aortic pressure, and left ventricular pressures were measured with the ring loose (off) and tightened (on). Mean regurgitant orifice area decreased by 86%, from 0.07 +/- 0.03 cm2 (ring loose, off) to 0.01 +/- 0.00 cm2 (ring tightened, on) [p < 0.01]. The regurgitant fraction decreased from 18 +/- 4% to 2 +/- 1% [p < 0.01]. The ring did not significantly affect stroke volume and aortic pressure. CONCLUSIONS: An ovine model of aortic root dilatation resulting in acute AI has been developed. In this model, application of an external, adjustable constricting aortic ring eliminated AI. An aortic ring may be a useful adjunct in reducing AI secondary to annular dilatation. PMID- 17720420 TI - Continued aortic aneurysmal expansion after thoracic endovascular stent-grafting. AB - We report the successful open repair of a thoracoabdominal aneurysm that had expanded after previous endovascular stenting. Aortic valve-sparing root replacement was performed as an initial step because the patient had significant aortic valve regurgitation caused by root enlargement. Continued aneurysmal dilatation after stenting of the thoracic aorta can lead to repair failure and therefore underscores the need for careful follow-up of patients after endografting. PMID- 17720421 TI - Aortic valve endocarditis by Capnocytophaga haemolytica. AB - We report a case of a 51-year-old patient with suspected prosthetic valve endocarditis. Capnocytophaga haemolytica was isolated in blood cultures and the repeated echocardiograms showed growth of vegetations and disruption of the proximal prosthetic valve suture line with progressive aortic regurgitation. The patient underwent a root debridement and replacement with a stentless bioprosthesis. PMID- 17720422 TI - Aortic elongation induced aortic stenosis (AEAS). AB - We present a case of a 71-year-old man who presented with aortic stenosis. This was pseudo-aortic obstruction resulting from the mitral valve subvalvular apparatus impacting into a normal aortic valve as a result of elongation of the ascending aorta. To place this case in context, we also provide a review of left ventricular outflow obstruction with an emphasis on subvalvular stenosis. PMID- 17720423 TI - Corrosion of pure titanium sternal wire. AB - Titanium and its alloys are considered reliable materials commonly used in heart surgeries. A patient had severe inflammation at the median sternotomy wound develop after open heart surgery. Sternal wires were removed and were found to be seriously corroded on most of the surface. Energy dispersive spectroscopy identified titanium as the only elemental component of the explanted wire with grade 2 purity, and the polarization curve showed satisfactory corrosion resistance similar to commercial pure titanium. Prolonged inflammation might have caused extensive corrosion of titanium in the present case. PMID- 17720424 TI - Hypoplastic circumflex retroesophageal right-sided cervical aortic arch with unusual vascular arrangement and severe coarctation. AB - We report the case of a 12-year-old boy with a hypoplastic retroesophageal circumflex right-sided cervical aortic arch and coarctation. After the incidental finding of a heart murmur when the boy was 9 years old, cardiac magnetic resonance showed a right-sided cervical aortic arch, hypoplastic transverse arch, and separate origin of the left common carotid, right common carotid, right vertebral, and right subclavian arteries. The left subclavian artery arose from the proximal descending aorta next to the coarctation. An extra-anatomical ascending to descending aorta tube graft was inserted through a right lateral thoracotomy with good results. PMID- 17720425 TI - Surgical treatment of persistent fifth aortic arch associated with interrupted aortic arch. AB - This study describes two cases of the rare congenital anomaly, persistent fifth aortic arch. Both cases involve boys (1 at 9 years of age and another at 7 months of age). To detect persistent fifth aortic arch with interrupted aortic arch, the following methods were used: echocardiogram, angiocardiography, and magnetic resonance imaging. In both cases the blood pressure between the upper and lower limbs differed. To relieve the obstruction of blood flow, each case was surgically repaired using patching or conduit interposition. Postoperative courses were uneventful. Two-year to 5-year follow-up examinations were positive showing that the anastomosis was unobstructed and the velocity of blood flow to the descending aorta was normal. PMID- 17720426 TI - Transaortic fine-needle aspiration of centrally located lung cancer under endoscopic ultrasound guidance: the final frontier. AB - We describe endoscopic ultrasound guided fine-needle aspiration of a mass adjacent to the descending thoracic aorta, which was performed without complication. PMID- 17720427 TI - Spontaneous hemothorax in a patient with neurofibromatosis type 1 and undiagnosed pheochromocytoma. AB - Spontaneous hemothorax in neurofibromatosis type 1 rarely occurs, is potentially life-threatening, and requires expedient management. We present a case of massive hemothorax in a patient with neurofibromatosis type 1 caused by spontaneous rupture of the right internal mammary artery. A subsequently diagnosed underlying pheochromocytoma may be implicated in rupture of the arterial wall. PMID- 17720428 TI - New modality of collapse therapy for pulmonary tuberculosis sequels: tissue expander. AB - Classical collapse therapy with extrapleural Lucite balls placement used for tuberculosis sequelae is associated with long term complications, such as migration of the foreign body. We report a new modality of collapse therapy for tuberculosis cavitation which may avoid this complication and which uses percutaneous tissue expanders. Postoperative course was uneventful and mid term follow-up confirmed the functional improvement without recurrence of the infection. This new modality of post-tuberculosis collapse therapy may allow treatment with fewer physical and physiologic sequelae of the residual cavities, and should reduce long term complications such as migration. PMID- 17720429 TI - Is previous thoracic sympathectomy a risk factor for exertional heat stroke? AB - We report the case of a physically fit young man who presented with severe, life threatening heat stroke after running a 10 km road race. He had previously received bilateral thoracic sympathectomy for axillary hyperhidrosis at another hospital, and was known to have upper body and limb anhidrosis. Thoracic sympathectomy can result in reduced sweating and disturbed peripheral vascular and heart rate responses. Patients should be warned that these mechanisms may play a role in the development of exertional heat stroke. PMID- 17720430 TI - One-stage excision of massive cervicomediastinal lymphangioma in the newborn. AB - We report the first neonate successfully treated with one-stage complete excision of massive cervicomediastinal lymphangioma producing alarming respiratory distress. Early postoperative course was complicated by refractory bilateral chylothorax, which effectively responded to insertion of external pleuroperitoneal shunts. At the 6-year follow-up, the child remains symptom free and recurrence free. One-stage resection for cervicomediastinal lymphangioma is curative and well tolerated even shortly after birth. PMID- 17720431 TI - Satisfactory results of diaphragmatic plication for bilateral phrenic nerve paralysis. AB - Bilateral diaphragmatic plication was performed in a 44-year-old man who underwent complete resection of a thymoma infiltrating the right lung, bilateral brachiocephalic vein, pericardium, and bilateral phrenic nerves. The plication procedure allowed him to be weaned from the ventilator on postoperative day 4. He demonstrated no restrictive or obstructive pattern of lung function, and after respiratory rehabilitation he returned to work full time 5 weeks after the operation. The present results indicate that ventilatory movement of the thoracic cage can compensate for loss of bilateral diaphragmatic ventilation for at least 18 months. PMID- 17720432 TI - Successful reconstruction of traumatic carinal tissue loss using the esophagus in an infant. AB - We present a case report of an infant who underwent successful reconstruction of a traumatic tracheal and carinal chemically induced corrosive injury using an esophageal flap to reconstruct the trachea and subsequently re-establishing gastrointestinal continuity with a colon interposition. PMID- 17720433 TI - Esophageal stents for iatrogenic esophageal perforations during cardiac surgery. AB - The usefulness and safety of transesophageal echocardiography during cardiac surgery have been well described in the literature. However, rare complications of this procedure can occur and should be familiar to surgeons and anesthesiologists. A series of two cases of esophageal perforation by echoprobe during cardiac surgery treated successfully by endoscopic stenting are reported. PMID- 17720434 TI - Successful conservative management of benign gastro-bronchial fistula after intrathoracic esophagogastrostomy. AB - Benign gastro-bronchial fistula is a rare and devastating complication of esophagectomy with gastric replacement. The most likely cause is a leak from the esophagogastric anastomosis with subsequent mediastinal abscess and rupture into the posterior wall of the tracheobronchial tree. The clinical presentation includes cough upon swallowing, fever, and recurrent pneumonia. Early surgical treatment is the standard of care. A unique case of chronic gastro-bronchial fistula is reported in this article. The patient, a 57-year-old woman, was referred from another hospital after 6 months of symptomatic therapy and total enteral nutrition. A self-expanding esophageal metal stent allowed exclusion of the fistula with symptom relief and return to oral alimentation. PMID- 17720435 TI - Deterioration of a tricuspid bioprosthesis due to adhesion of the native valve. PMID- 17720436 TI - A case of endobronchial and cutaneous metastases. PMID- 17720437 TI - Ablation of atrial fibrillation with minimally invasive mitral surgery. AB - With the advent of minimally invasive mitral valve surgery, transeptal exposure of the mitral valve has become increasingly popular. While this approach provides excellent exposure of the mitral valve, it necessitates development of novel strategies for concomitant ablation in patients with atrial fibrillation. We describe a technique for creation of a biatrial lesion set for atrial fibrillation ablation that is easily employed using the transeptal approach to the mitral valve. PMID- 17720438 TI - Posterior leaflet extension with an autologous pericardial patch in rheumatic mitral insufficiency. AB - We describe our technique of posterior leaflet extension with an autologous pericardial patch in patients suffering from rheumatic mitral regurgitation. Several simple rules have allowed us to achieve satisfying long-term results. PMID- 17720439 TI - An extra anatomic, close chest approach to manage an aortic arch aneurysm in an 88-year-old woman. AB - Repair of thoracic arch aneurysms in the octogenarian is associated with a high morbidity and mortality. In this report we describe a minimally invasive approach to repair and arch aneurysm using an endoluminal graft with an extrathoracic, extra anatomic de-branching of the arch vessels. The advantage of this technique includes avoidance of a median sternotomy, cardiopulmonary bypass, and circulatory arrest with a rapid postoperative recovery. PMID- 17720440 TI - Use of bovine albumin-glutaraldehyde glue in cardiovascular surgery. AB - As with any new surgical device, effectiveness requires both an understanding of its characteristics and proper technique of application. This report details application techniques from the author's experience for the use of bovine albumin glutaraldehyde glue in a variety of cardiovascular surgical cases. PMID- 17720441 TI - Partial median "I" sternotomy: minimally invasive alternate approach for aortic valve replacement. AB - Minimally invasive aortic valve replacement using the inversed L-like partial upper sternotomy has evolved during the last 10 years. It is performed with excellent results with regard to sternal stability and cosmesis. However, the lateral incision may result in sternal overriding, instability, or fracture. We present an alternate minimally invasive approach to aortic valve replacement. We performed a partial median "I" sternotomy in 30 consecutive patients: After a 6- to 8-cm skin incision, the sternum was incised from the jugulum downward to the corpus, ending at the level of the fourth or fifth intercostal space. No lateral incision of the sternum was performed. The access to the heart and aorta was excellent. During the postoperative course and during follow-up, clinical examination revealed sternal stability and normal wound healing in all patients. These results show that the partial median I sternotomy can be performed safely and provides excellent clinical and cosmetic results. PMID- 17720442 TI - Rigid plate fixation of the sternum. AB - Sternotomy is the most common osteotomy performed worldwide and has traditionally been closed by wire circlage. Recent studies have demonstrated the superiority of internal plate fixation both in promoting bony stability and osteosynthesis and in decreasing the incidence of postoperative mediastinitis. Despite its advantages, this method of sternal closure has not yet gained widespread use. We describe a simple technique of sternal closure using plates secured with screws. PMID- 17720443 TI - Surgical assessment and intraoperative management of mediastinal lymph nodes in non-small cell lung cancer. AB - Mediastinal lymph node status has important prognostic and therapeutic implications for nonsmall cell lung cancer patients. Consequently, an accurate pathologic assessment of mediastinal lymph nodes for metastasis is essential. Despite the significance of nodal assessment, practice patterns among surgeons vary widely. Therefore we reviewed the literature to provide evidence-based recommendations regarding the ideal means and extent of preoperative and intraoperative pathologic mediastinal lymph node staging in non-small cell lung cancer patients. We found that the most sensitive and accurate intraoperative method is a complete mediastinal lymph node dissection. Pathologic evaluation of at least 10 mediastinal lymph node from at least three stations should be performed at the time of surgery. PMID- 17720445 TI - Should a patient with acute aortic dissection type A go to the intensive care unit or operating room? PMID- 17720447 TI - Can the risk associated with surgery in type A aortic dissection be predicted accurately? PMID- 17720449 TI - Minimally invasive aortic valve replacement: a word of caution. PMID- 17720450 TI - The need for pacemaker implantation after using a superior transseptal approach: letter 1. PMID- 17720452 TI - Superior septal approach for mitral valve surgery: letter 2. PMID- 17720453 TI - Monaldi's intracavitary decompression and its modifications. PMID- 17720454 TI - Tuberculous pericarditis after coronary artery bypass graft. PMID- 17720456 TI - Spontaneous zygogenesis, a wide-ranging mating process in bacteria. AB - Spontaneous zygogenesis (or Z-mating) in Escherichia coli, unlike F-mediated conjugation, promotes formation of complete zygotes. Most Z-mating products have proven to be phenotypically unstable, losing part of the phenotype for which they were selected. Persistent Z-mating products appear as stable genetic recombinants or yield subclones of two types: either both parental types or one of them plus a recombinant type, and the ability to promote spontaneous zygogenesis can appear in all emerging types. Here it is shown that spontaneous zygogenesis-promoting E. coli strains can Z-mate with strains of Shigella flexneri, Salmonella enterica Serovar Typhimurium and Serratia marcescens, giving rise to products that behave like those of homospecific Z-matings. When genetic recombination was prevented in products of Z-mating between E. coli and S. enterica or S. marcescens, phenotype switching was observed in purified isolates exhibiting a single phenotype, thus providing further evidence of interspecies genotypic mixing. The presence of two distinct replicons within a cell introduces a new situation that contrasts with classical conjugation between heterologous strains, where the partially transferred chromosomal segment is subject to restriction, is unable to replicate and is limited in genetic recombination. PMID- 17720457 TI - Characterization of BctA, a mating apparatus protein required for transfer of the Bacteroides fragilis conjugal element BTF-37. AB - We have previously described the identification of BTF-37, an autonomously transferable chromosomal element isolated from Bacteroides fragilis clinical isolate LV23. In this study, we determined that BTF-37 harbors a 16kb conjugal transfer-encoding region that contains an almost identical copy of a previously identified Bacteroides sp. conjugation-specific gene bctA. BctA has been shown to be required for conjugation in other Bacteroides sp. strains, but no information is available regarding its function. We now report strain distribution and gene expression profiles of bctA. The bctA gene was present in conjugative transposon harboring B. fragilis strains, but not on a non-transferable B. fragilis plasmid. We also showed that recombinant BctA predominantly localized to the bacterial membrane, and that its N-terminal 32 amino acids were cleaved in an Escherichia coli protein expression system, indicating the presence of a signal sequence. Expression of bctA consistently increased ~3-fold upon pre-exposure of conjugating B. fragilis LV23 to subinhibitory concentrations of tetracycline. Maximum expression occurred 60min post-tetracycline induction, which also coincided with the time at which highest conjugation frequencies were seen for strain LV23. Based on localization, signal sequence and tetracycline inducibility, our results indicate that BctA is indeed an important member of the Bacteroides conjugal apparatus, since its gene is regulated by conditions that specifically control conjugation. PMID- 17720459 TI - Brain structural changes in schizophrenia patients with persistent hallucinations. AB - Schizophrenia is characterised by the presence of a heterogeneous range of symptoms. Although there is a consensus regarding ventricular enlargement and regional grey matter deficits, the brain structural correlates of specific symptoms, such as auditory hallucinations, are not clearly defined. We used an automated voxel-wise analysis of dual-echo spin-echo MRI data from 28 patients with schizophrenia characterised by persistent hallucinations and 32 healthy controls. Patients demonstrated grey matter (GM) volume decrements in the insula bilaterally, and in the right superior temporal and fusiform gyri, and left inferior temporal gyrus. With the exception of the insula, these GM volume losses were correlated with severity of auditory hallucinations. GM excesses were observed in the right caudate nucleus and middle temporal gyrus. White matter deficits were observed adjacent to the left superior temporal gyrus, in the right internal capsule and inferior longitudinal fasciculus. These findings support the proposition that there are structural changes in the neural circuits underlying broader processing of affect-laden information in patients with schizophrenia prone to experiencing auditory hallucinations. Such deficits may obscure important cues for recognition of internal speech, contributing to failures of self-monitoring. PMID- 17720458 TI - Characterization of hbzE-encoded gentisate 1,2-dioxygenase from Pseudomonas alcaligenes NCIMB 9867. AB - Pseudomonas alcaligenes NCIMB 9867 (strain P25X) is known to synthesize two isofunctional gentisate 1,2-dioxygenases (GDO; EC 1.13.11.4) as well as other enzymes involved in the degradation of xylenols and cresols via the gentisate pathway. The hbzE gene encoding what is possibly the strictly inducible gentisate 1,2-dioxygenase II (GDO-II) was cloned, overexpressed and purified as a hexahistidine fusion protein from Escherichia coli. Active recombinant GDO-II had an estimated molecular mass of 150kDa and is likely a tetrameric protein with a subunit mass of approximately 40kDa, similar to the previously characterized gentisate 1,2-dioxygenase I (GDO-I) encoded by xlnE. However, GDO-II was unable to utilize gentisate that is substituted at the carbon-4 position, unlike GDO-I which had broader substrate specificity. GDO-II also possessed different kinetic characteristics when compared to GDO-I. The hbzE-encoded GDO-II shared higher sequence identities (53%) with GDOs from Ralstonia sp. U2 and Polaromonas naphthalenivorans CJ2, compared with only 35% identity with the xlnE-encoded GDO I. The hbzE gene was found to be part of a cluster of nine genes including the putative regulatory gene designated hbzR, which encodes an LysR-type regulator and is divergently transcribed from the other genes of the hbzHIJKLFED cluster. PMID- 17720460 TI - Surface immobilization of chondroitin 6-sulfate/heparin multilayer on stainless steel for developing drug-eluting coronary stents. AB - A thin layer of gold was sputtered onto SUS316L stainless steel (SS) sheet. After thiolizing the Au layer with dimercaptosuccinic acid (DMSA), layers of chondroitin 6-sulfate (ChS) and heparin (HEP) were alternatively immobilized on the Au-treated SS. The resulting stent would be both anti-atherogenic and anti thrombogenic. After repeating one to five cycles, one to five layers of polyelectrolyte complex (PEC) of ChS/HEP were successfully fabricated. A model drug, sirolimus, was loaded in the ChS/HEP layers. The SS-ChS-HEP surface was examined by X-ray photoelectron spectroscopy (XPS), contact angle, and atomic force microscopy (AFM) measurement. Biological tests including hemocompatibility, drug release pattern, and the inhibition of smooth muscle cell proliferation were also performed. The results show that the multilayer of ChS/HEP exhibits longer blood clotting time than pure SS substrates. Therefore, this biopolymer multilayer can avoid thrombosis on the stainless. The releasing rate of sirolimus can be controlled through the number of ChS/HEP PEC layers. With a five-layer coating, sirolimus can be released continuously for more than 20 days. Furthermore, the multilayer ChS/HEP loaded with sirolimus can suppress specifically to the growth of smooth muscle cells to avoid restenosis. This suggests that the PEC multilayer of ChS/HEP modified-SS could be applied in making drug-eluting stents. PMID- 17720461 TI - Stability of collagen with polyols against guanidine denaturation. AB - The effect of polyol osmolytes such as erythritol, xylitol and sorbitol on the protection of collagen against guanidine hydrochloride (GdmCl) was studied using circular dichroism and fluorescence spectroscopy. Collagen was denatured by various concentrations of GdmCl in the presence of polyols. The absorbance was high for GdmCl treated collagen than native and polyols treated analogue. Fluorescence emission properties were studied at the excitation wavelength of 235 nm. The emission wavelength is red shifted from 308 to 370 nm for GdmCl treated collagen with polyols. Increasing the concentration of GdmCl did not affect the peak position. CD studies proved that the aggregation of collagen in the presence of lower concentrations of GdmCl. At higher concentrations of GdmCl due to the loss of secondary structure no clear CD spectra were observed. This shows that the unfolding of collagen is closely related to GdmCl concentrations. The ability of the polyols to protect collagen against guanidine denaturation decreased in order from erythritol to xylitol to sorbitol. The presence of OH group in the solvent structure is important for stabilization of collagen due to the formation of additional stabilizing hydrogen bonds. PMID- 17720462 TI - Phylogeny of trichostome ciliates (Ciliophora, Litostomatea) endosymbiotic in the Yakut horse (Equus caballus). AB - Ciliates of the subclass Trichostomatia inhabit the fermentative regions of the digestive tract of herbivores. Most available small subunit ribosomal RNA (SSrRNA) gene sequences of trichostomes are from species isolated from the rumen of cattle or sheep and from marsupials. No ciliate species endosymbiotic in horses has yet been analyzed. We have sequenced the SSrRNA genes of five ciliate species, isolated from the cecum and colon of four Yakut horses: Cycloposthium edentatum, Cycloposthium ishikawai, Tripalmaria dogieli, Cochliatoxum periachtum, and Paraisotricha colpoidea. Based on their morphology, Cycloposthium, Tripalmaria, and Cochliatoxum are classified as Entodiniomorphida, while Paraisotricha is considered a member of the Vestibuliferida. Phylogenetic analyses using Bayesian inference, distance, and parsimony methods confirm these placements. The two Cycloposthium species cluster together with the published Cycloposthium species isolated from a wallaby in Australia. Tripalmaria and Cochliatoxum branch as a sister group to or basal within the Entodiniomorphida. The Vestibuliferida remain paraphyletic with Paraisotricha and Balantidium branching basal to all other trichostome species, but not closely related to Isotricha and Dasytricha. PMID- 17720463 TI - Indirect benefits for choosy female grasshoppers (Chorthippus biguttulus)? AB - Since direct benefits are likely to be absent in the grasshopper Chorthippus biguttulus, indirect genetic benefits are a potential explanation for costly female preference. Choosy females may improve their fitness in terms of enhanced attractiveness of sons alone or additionally by improved viability of offspring. We tested the predictions of these two hypotheses by comparing attractiveness related song traits and viability in offspring of attractive and unattractive grasshopper males. The experiment was conducted with larvae reared under semi natural lab conditions in one year and under natural conditions in the field in the following year. If reared under natural conditions no significant differences in viability and song traits between offspring of attractive and unattractive males could be found. Offspring reared in the lab produced calling songs with a significantly more exact song rhythm when sired by attractive males than offspring of unattractive males. Offspring of attractive males should thus have a theoretical advantage in mate choice, which, however, did not translate into higher attractiveness values in acoustic female choice experiments. Therefore our experiments could not resolve whether female choice in C. biguttulus evolved according to the sexy son hypothesis. Since viability in offspring of attractive males did not differ from offspring of unattractive males, "good genes" seems unlikely to be the underlying mechanism of female choice. PMID- 17720464 TI - The correlation between immunocompetence and an ornament trait changes over lifetime in Panorpa vulgaris scorpionflies. AB - The immunocompetence-handicap hypothesis posits that costly male ornament traits might function to signal superior heritable immunocompetence to females. Quite a number of studies have aimed at testing this hypothesis. Yet the empirical data obtained so far are ambiguous. Many studies analysed the phenotypic correlation between handicap expression and immunocompetence at the same time point. However, since immunocompetence may change drastically over an individual's lifetime, such a singular measurement may not represent genetic differences among males and the benefits of choosing handicapped males for females might thus be weak. Here, I tested the correlation of a potential immunocompetence-handicap, the production of salivary secretions as nuptial gifts in a scorpionfly (Panorpa vulgaris), with immunocompetence at two different time points. I found a positive correlation with the handicap, but only if immunocompetence was measured shortly after expression of the handicap, i.e. briefly after mating in 2 weeks old scorpionflies. By contrast, there was no correlation with immunocompetence of the same flies at a younger age, i.e. shortly after adult emergence and a weak, insignificant trend for increased immunocompetence in offspring. These results are in agreement with positive phenotypic correlations between immunocompetence and handicap expression reported from other species, but advise caution when generalizing such one-time correlations. PMID- 17720465 TI - Interference of raw milk autochthonous microbiota on the performance of conventional methodologies for Listeria monocytogenes and Salmonella spp. detection. AB - Pathogen detection in foods by reliable methodologies is very important to guarantee microbiological safety. However, peculiar characteristics of certain foods, such as autochthonous microbiota, can directly influence pathogen development and detection. With the objective of verifying the performance of the official analytical methodologies for the isolation of Listeria monocytogenes and Salmonella in milk, different concentrations of these pathogens were inoculated in raw milk treatments with different levels of mesophilic aerobes, and then submitted to the traditional isolation procedures for the inoculated pathogens. Listeria monocytogenes was inoculated at the range of 0.2-5.2 log CFU/mL in treatments with 1.8-8.2 log CFU/mL. Salmonella Enteritidis was inoculated at 0.9 3.9 log CFU/mL in treatments with 3.0-8.2logCFU/mL. The results indicated that recovery was not possible or was more difficult in the treatments with high counts of mesophilic aerobes and low levels of the pathogens, indicating interference of raw milk autochthonous microbiota. This interference was more evident for L. monocytogenes, once the pathogen recovery was not possible in treatments with mesophilic aerobes up to 4.0 log CFU/mL and inoculum under 2.0 log CFU/mL. For S. Enteritidis the interference appeared to be more non-specific. PMID- 17720466 TI - Cytokines and growth factors in airway remodeling in asthma. AB - Airway remodeling in asthma is defined by several structural changes including epithelial cell mucus metaplasia, an increase in peribronchial smooth muscle mass, subepithelial fibrosis, and angiogenesis. Cytokines, chemokines, and growth factors released from inflammatory and structural cells in the airway are considered to play a pivotal role in the development of remodeling. Studies of allergen induced airway remodeling in transgenic mice suggest an important role for TGF-beta, VEGF, Th2 cytokines (IL-5, IL-9, IL-13), and epithelial derived NF kappaB regulated chemokines in airway remodeling. Although studies of bronchial biopsies from human asthmatics also demonstrate expression of TGF-beta, VEGF, IL 5, IL-9, IL-13, and NF-kappaB regulated chemokines, further human intervention studies are required in which individual cytokines or chemokines are neutralized to define their role in airway remodeling. PMID- 17720467 TI - Cellular mechanisms underlying acute graft rejection: time for reassessment. AB - Rejection of transplanted organs depends on an orchestrated immune response to histocompatibility antigens expressed by the grafted tissue. Effector mechanisms primarily responsible for the rejection process classically involve type 1 helper CD4(+) T cells, cytotoxic CD8(+) T cells and antibodies. Experimental studies revealed alternative mechanisms of rejection that implicate type 2 helper CD4(+) T cells and memory CD8(+) T cells as well as cells belonging to the innate immune system including natural killer cells, eosinophils and neutrophils. Furthermore, local inflammation associated with rejection is tightly regulated at the graft level by regulatory T cells and mast cells. The redundancy of rejection mechanisms explains the difficulty to induce transplantation tolerance and to develop reliable biomarkers for prediction of allograft outcome. PMID- 17720468 TI - Epigenetic regulation of airway inflammation. AB - Diverse cellular functions including the regulation of inflammatory gene expression, DNA repair and cell proliferation are regulated by epigenetic changes. Transcriptional co-activators possess intrinsic histone acetyltransferase (HAT) activity, and histone acetylation plays a major role in inflammatory gene expression. Other marks such as histone methylation are also associated with gene induction and gene repression. Recent evidence implicates histone acetylation and methylation as being crucial for the development of tolerance in macrophages and CpG methylation for T regulatory cell development and function. The expression of the enzymes that lay down or remove these epigenetic marks have not been well studied in human airways disease, but reduced HDAC2 expression and activity is reported in lung macrophages, biopsies and blood cells from patients with COPD, severe asthma and smoking asthma. In vitro, inhibitors of histone deacetylases (HDAC) often lead to a further induction of inflammatory gene expression. This is not always the case, however, as HATs and HDACs also target non-histone proteins particularly transcription factors to alter their activity. Furthermore, trichostatin A, an HDAC inhibitor, can reduce inflammation in a murine model of allergic asthma. This effect of HDAC inhibitors may be due to their effects on cell death acting through acetylation of non histone proteins. The role of epigenetic modifications in inflammatory gene expression and in the control of cell function in the airways is becoming clearer. Targeting specific enzymes involved in this process may lead to new therapeutic agents, in particular, in situations where current anti-inflammatory therapies are currently suboptimal. PMID- 17720469 TI - Interrupter resistance short-term repeatability and bronchodilator response in preschool children. AB - Interrupter resistance (Rint) technique can be easily and successfully performed in preschool children. The establishment of Rint short-term repeatability is essential to interpret any Rint change after a pharmacological intervention. AIMS OF THE STUDY: In preschool children with asthma or chronic cough: (1) to assess two indices of short-term repeatability: (a) intra-measurement and (b) within occasion between-test repeatability; (2) to study the relationship between short term repeatability and bronchodilator response (BDR). RESULTS: Rint intra measurement repeatability assessed by the coefficient of variation was similar at baseline and after bronchodilator in asthmatics and in coughers (median 10% and 12%, respectively). There was no significant difference between asthmatics and coughers for both coefficient of repeatability (CR) (0.25 kPa L(-1)s and 32% of predicted vs 0.16 kPa L(-1) s and 21% of predicted, respectively) and BDR (median -14.7% vs -21.1% of predicted, respectively). However, in 20% of the study children, baseline variability of Rint modified the significance of the BDR. CONCLUSION: In the present study, Rint short-term repeatability was similar to that of previous studies. Similar Rint repeatability in coughers and in asthmatic children favored the use of asthmatic CR for both populations, and a -35% cut-off as a positive BDR. In 20% of study children, baseline Rint variability could influence the significance of the BDR. In order to improve assessment of BDR using Rint, further studies are needed (1) to compare the variability of Rint to other resistance measurement techniques and (2) to define the best method for Rint calculation and for expression of BDR. PMID- 17720470 TI - Methacholine challenge in pre-school children--which outcome measure? AB - The aim of our study was to evaluate the utility of interrupter resistance (R(int)), transcutaneous oximetry and auscultation as outcome measures for a recently suggested tripling-dose methacholine (Mch) challenge in pre-school children. We studied 57 children aged 3-6 years. R(int) was measured at baseline and after each Mch dose. Oxygen saturation (SaO(2)) and transcutaneous oxygen pressure (tcpO(2)) were monitored during the challenge. Mch concentrations of 0.22, 0.66, 2.0, 6.0 and 18.0 mg/ml were nebulised during tidal breathing. The challenge was terminated if there was wheeze, SaO(2) below 91% or persistent cough; this final Mch dose was considered as PCW. Nine healthy children, 17 with cough and 25 with wheeze performed the study up to the point of PCW or all five Mch inhalations. If a change of 20% of predicted R(int) or termination by wheeze, desaturation or cough is taken as a completed test, then 39 out of 51 children (78%) had adequate R(int) measurements on each occasions from start to completion. The success rate for tcpO(2) measurements was similar: 38 out of 51 (76%) had complete tcpO(2) data until a 15% fall of tcpO(2) or clinical endpoint was reached. Using the above-mentioned cut-off levels significant change in R(int) or tcpO(2) preceded PCW in most of the cases. Both R(int) and tcpO(2) measurements may allow detection of bronchial hyper-responsiveness at lower Mch doses and also provide a less subjective measure, but will not be feasible in all children. PMID- 17720471 TI - Carbon nanotubes and glucose oxidase bionanocomposite bridged by ionic liquid like unit: preparation and electrochemical properties. AB - For their biocompatibility and potential bionanoelectronic applications, integration of carbon nanotubes (CNTs) with biomolecules such as redox enzyme is highly anticipated. Therein, CNTs are expected to act not only as an electron transfer promoter, but also as immobilizing substrate for biomolecules. In this report, a novel method for immobilization of biomolecules on CNTs was proposed based on ionic interaction, which is of universality and widespread use in biological system. As illustrated, glucose oxidase (GOD) and single-walled carbon nanotubes (SWNTs) were integrated into a unitary bionanocomposite by means of ionic liquid-like unit on functionalized SWNTs. The resulted bionanocomposite illustrated better redox response of immobilized GOD in comparison of that prepared by weak physical absorption without ionic interaction. As a potential application of concept, the electrochemical detection of glucose was exemplified based on this novel bionanocomposite. PMID- 17720472 TI - Successively amplified electrochemical immunoassay based on biocatalytic deposition of silver nanoparticles and silver enhancement. AB - A successively signal-amplified electrochemical immunoassay has been reported on the basis of the biocatalytic deposition of silver nanoparticles with their subsequent enlargement by nanoparticle-promoted catalytic precipitation of silver from the silver-enhancer solution. The immunoassay was carried out based on a heterogeneous sandwich procedure using polystyrene microwells to immobilize antibody. After all the processes comprising the formation of immunocomplex, biocatalytic deposition of silver nanoparticles and following silver enhancement were completed, the silver on polystyrene microwells was dissolved and quantified by anodic stripping voltammetry (ASV). The effect of relevant experimental conditions, including the concentration of ascorbic acid 2-phosphate (AA-p) substrate and Ag(I) ions, the biocatalytic deposition time, and of crucial importance, the silver enhancement time, were investigated and optimized. The anodic stripping peak current was proportional to the concentration of human IgG in a dynamic range of 0.1-10 ng ml(-1) with a detection limit of 0.03 ng ml(-1). Scanning electron microscope (SEM) was applied to characterize the silver nanoparticles before and after silver enhancement on the surface of polystyrene microplates. By coupling the highly catalytic effect of enzyme and nanoparticles to successively amplify the analytical signal, the sensitivity of immunoassay was enhanced so dramatically that this approach would be a promising strategy to achieve a lower detection limit for bioassays. PMID- 17720473 TI - Whole blood optical biosensor. AB - The future of rapid point-of-care diagnostics depends on the development of cheap, noncomplex, and easily integrated systems to analyze biological samples directly from the patient (e.g. blood, urine, and saliva). A key concern in diagnostic biosensing is signal differentiation between non-specifically bound material and the specific capture of target molecules. This is a particular challenge for optical detection devices in analyzing complex biological samples. Here we demonstrate a porous silicon (PSi) label-free optical biosensor that has intrinsic size-exclusion filtering capabilities which enhances signal differentiation. We present the first demonstration of highly repeatable, specific detection of immunoglobulin G (IgG) in serum and whole blood samples over a typical physiological range using the PSi material as both a biosensor substrate and filter. PMID- 17720475 TI - Electrochemical study of ferrocenemethanol-modified layered double hydroxides composite matrix: application to glucose amperometric biosensor. AB - A novel amperometric glucose sensor based on co-immobilization of ferrocenemethanol (MeOHFc) and glucose oxidase (GOD) in the layered double hydroxides (LDHs) was described. MeOHFc immobilized in LDHs played effectively the role of an electron shuttle and allowed the detection of glucose at 0.25 V (versus SCE), with dramatically reduced interference from easily oxidizable constituents. The sensor (LDHs/MeOHFc/GOD) exhibited a relatively fast response (response time was about 5s), low detection limit (3 microM), and high sensitivity (ca. 60 mA M(-1)cm(-2)) with a linear range of 6.7 x 10(-6) to 3.86 x 10(-4)M of glucose. Apparent Michaelis-Menten constant was calculated to be 2.25 mM. PMID- 17720474 TI - A biofuel cell harvesting energy from glucose-air and fruit juice-air. AB - The membraneless biofuel cell (BFC) is facile prepared based on glucose oxidase and laccase as anodic and cathodic catalyst, respectively, by using 1,1' dicarboxyferrocene as the mediators of both anode and cathode. The BFC can work by taking glucose as fuel in air-saturated solution, in which air serves as the oxidizer of the cathode. More interestingly, the fruit juice containing glucose, e.g. grape, banana or orange juice as the fuels substituting for glucose can make the BFC work. The BFC shows several advantages which have not been reported to our knowledge: (1) it is membraneless BFC which can work with same mediator on both anode and cathode; (2) fruit juice can act as fuels of BFCs substituting for usually used glucose; (3) especially, the orange juice can greatly enhance the power output rather than that of glucose, grape or banana juice. Besides, the facile and simple preparation procedure and easy accessibility of fruit juice as well as air being whenever and everywhere imply that our system has promising potential for the development and practical application of BFCs. PMID- 17720476 TI - Identification of viral microRNAs. AB - Given the important function of microRNAs (miRNAs) in the control of gene expression, it is not surprising to find that some viruses encode their own miRNAs. Although the function of the overwhelming majority of these miRNAs remains unknown, at least some of them are expected to play crucial roles in the viral life cycle, and hence there is great interest in identifying novel viral miRNAs. The majority of currently known viral (and host) miRNAs have been identified by cloning of small RNAs, but, due to their small size, viral genomes are especially amenable to alternative methods based on the computational prediction of miRNA candidates. Here, we provide a detailed protocol on how to use computational prediction methods in conjunction with high-throughput microarray analysis to detect miRNAs in viral genomes. PMID- 17720477 TI - Robust machine learning algorithms predict microRNA genes and targets. AB - MicroRNAs (miRNA) are nonprotein coding RNAs with the potential to regulate the gene expression of thousands of protein coding genes. Current estimates suggest the number of miRNA genes may be twice of what is currently known, and the mechanisms governing miRNA targeting remain elusive. Machine learning algorithms can be used to create classifiers that capture the characteristics of verified examples to determine whether genomic hairpins are similar to verified miRNA genes or if message 3'UTRs possess known target characteristics. Algorithms can never replace biological verifications, but should always be used to guide experimental design. This chapter focuses on potential problems that must be addressed when machine learning is used and follows a practical approach to demonstrate how support vector machines and genetic programming can predict miRNA genes and targets. PMID- 17720478 TI - Identification of virally encoded microRNAs. AB - RNA silencing is a widespread phenomenon that regulates gene expression at different levels. Small RNA molecules are at the core of all RNA silencing pathways and can be grouped in distinct families depending on their chemical properties and their mode of action. Among these small RNAs, microRNAs (miRNAs) represent one of the most extensively studied classes in animals. These tiny endogenous RNAs regulate gene expression posttranscriptionally by cleaving the targeted transcript or by interfering with its translation. miRNAs are found in plants and animals and have been identified in mammalian viruses. This indicates that mammalian viruses exploit the host RNA silencing machinery to produce miRNAs that have the potential to act both on the infected host genome and on the viral genome. The techniques used for identification of viral miRNAs mostly parallel what is used for identifying cellular miRNAs. The use of prediction algorithms followed by validation has been successful. A more direct and nonbiased way of identifying viral miRNAs consists of cloning and sequencing small RNA libraries from virally infected cells or tissues. PMID- 17720479 TI - Computational methods for microRNA target prediction. AB - The discovery of microRNAs (miRNAs) has introduced a new paradigm into gene regulatory systems. Large numbers of miRNAs have been identified in a wide range of species, and most of them are known to downregulate translation of messenger RNAs (mRNAs) via imperfect binding of the miRNA to a specific site or sites in the 3' untranslated region (UTR) of the mRNA. Identification of genes targeted by miRNAs is widely believed to be an important step toward understanding the role of miRNAs in gene regulatory networks. As part of the effort to understand interactions between miRNAs and their targets, computational algorithms have been developed based on observed rules for features such as the degree of hybridization between the two RNA molecules. These in silico approaches provide important tools for miRNA target detection, and together with experimental validation, help to reveal regulated targets of miRNAs. Here, we summarize the knowledge that has been accumulated about the principles of target recognition by miRNAs and the currently available computational methodologies for prediction of miRNA target genes. PMID- 17720480 TI - In vitro and in vivo assays for the activity of Drosha complex. AB - MicroRNA (miRNA) genes are transcribed into long primary transcripts (pri-miRNAs) that get processed into mature miRNAs of about 22 nt in length by two different ribonuclease (RNase) III enzymes, Drosha and Dicer. Various experimental protocols have been developed and modified for genetic and biochemical analyses for microRNA processing. Here we describe the methods for the analysis of pri miRNA processing that is mediated by Drosha and its cofactor, DiGeorge Syndrome Critical Region Gene 8 (DGCR8). PMID- 17720481 TI - Microarray analysis of miRNA gene expression. AB - MicroRNAs (miRNAs) are small, noncoding RNAs that regulate the expression of target mRNAs. Although thousands of miRNAs have been identified, few have been functionally linked to specific biological pathways. Microarray-based expression analysis is an ideal strategy for identifying candidate miRNAs that correlate with biological pathways and for generating molecular signatures of disease states. This chapter will describe a simple, low-cost microarray platform optimized for miRNA expression analysis. PMID- 17720482 TI - Cloning and detecting signature microRNAs from mammalian cells. AB - MicroRNAs (miRNAs) are about 19- to 24-nucleotides long noncoding regulatory small RNAs that could silence target gene expression through base pairing to the complementary sequences in the 3' untranslated region (3'UTR) of targeted genes. They are evolutionally conserved and play an important regulatory role in embryogenesis, cell differentiation, and proliferation. They are also involved in pathogenesis and progression of some human diseases. There are about 1000 human miRNAs predicted today, and it is estimated that they could target about 30% of all human transcripts. Profiling the miRNAs that are expressed in the experimental cells became an important issue as different cells express different signature miRNAs or express the same miRNAs at different level. Small RNA cloning is a reliable way to characterize those tissue- or cell-specific signature miRNAs. This chapter describes a relatively nonlaborious polyadenylation-mediated complementary DNA (cDNA) cloning method that will identify most of the small RNAs expressed in the cells of interest. This procedure can also be used to verify bioinformatic predictions of miRNAs/small interfering RNAs (siRNAs) as well as to identify new miRNAs/siRNAs. PMID- 17720484 TI - Analysis of small RNA profiles during development. AB - Small RNAs ranging in size between 20 and 32 nt regulate gene expression through chromatin modification, mRNA degradation, and translational repression. Three major classes of small RNAs have been characterized: microRNAs (miRNAs), short interfering RNAs (siRNAs), and Piwi-interacting RNAs (piRNAs). miRNAs are expressed in a developmentally regulated and tissue-specific manner and are involved in development and cell differentiation. siRNAs are mainly involved in defense against transposons and viruses. piRNAs are expressed in germ cells and stem cells and are thought to repress transposition of retrotransposons. In this chapter, we describe the methods of small RNA cloning, annotation and classification, and their expression analysis during development. PMID- 17720483 TI - Approaches for studying microRNA and small interfering RNA methylation in vitro and in vivo. AB - The biogenesis of microRNAs (miRNAs) in plants is similar to that in animals, however, the processing of plant miRNAs consists of an additional step, the methylation of the miRNAs on the 3' terminal nucleotides. The enzyme that methylates Arabidopsis miRNAs is encoded by a gene named HEN1, which has been shown genetically to be required for miRNA biogenesis in vivo. Small interfering RNAs (siRNAs) are also methylated in vivo in a HEN1-dependent manner. Our biochemical studies demonstrated that HEN1 is a methyltransferase acting on both miRNAs and siRNAs in vitro. HEN1 recognizes 21 to 24 nt small RNA duplexes, which are the products of Dicer-like enzymes, and transfers a methyl group from S adenosylmethionine (SAM) to the 2' OH of the last nucleotides of the small RNA duplexes. Here we describe methods to characterize the biochemical activities of the HEN1 protein both in vitro and in vivo, and methods to analyze the methylation status of small RNAs in vivo. PMID- 17720485 TI - Dissecting microRNA-mediated gene regulation and function in T-cell development. AB - MicroRNAs (miRNAs) are abundant approximately 22-nucleotide regulatory RNAs encoded in animal genomes. They are thought to exhibit diverse biological functions in animals by targeting messenger RNAs (mRNAs) for degradation or translational repression. Here we use T-cell development as a model to illustrate methods and strategies for dissecting the post transcriptional gene regulatory networks controlled by miRNAs and their roles in the differentiation of T-cell precursors. The process involves the identification of miRNA genes in rare T-cell progenitors, determining miRNA expression during T-cell development, characterizing miRNA function in T-cell development using an in vitro assay, and identifying functionally relevant gene(s) regulated by miRNAs. PMID- 17720486 TI - Investigation of microRNA alterations in leukemias and lymphomas. AB - Alterations in miRNA genes play a critical role in the pathophysiology of many, perhaps all, human cancers: cancer initiation and progression can involve alterations of microRNA genes (miRNAs) encoding small noncoding RNAs that can regulate gene expression. The main mechanism of microRNoma (defined as the full complement of microRNAs present in a genome) alteration in cancer cell seems to result in aberrant gene expression characterized by abnormal levels of expression for mature and/or precursor miRNA sequences in comparison with the corresponding normal tissues. Loss or amplification of miRNA genes has been reported in a variety of cancers, and altered patterns of miRNA expression may affect cell cycle and survival programs. The causes of the widespread differential expression of miRNA genes between malignant and normal cells can be explained by the genomic location of these genes in cancer-associated genomic regions, by epigenetic mechanisms as well as by alterations of members of the processing machinery. Germline and somatic mutations in miRNAs or polymorphisms in the mRNAs targeted by miRNAs may also contribute to cancer predisposition and progression. miRNAs expression profiling has been exploited to identify miRNAs potentially involved in the pathogenesis of human cancers and has allowed the identification of signatures associated with diagnosis, staging, progression, prognosis, and response to treatment of human tumors. Here we present a flowchart of principal steps to produce, analyze, and understand the biological significance of miRNA microarray data. PMID- 17720487 TI - Discovery of pathogen-regulated small RNAs in plants. AB - Small RNAs have emerged as one of the most important regulators for gene expression in eukaryotes. Small RNA-mediated gene silencing has been shown to play an essential role in antiviral defense in both plant and animal systems (Li and Ding, 2005; Voinnet, 2005; Wang et al., 2006). These viral RNA-generated small interfering RNAs (siRNAs) are extragenomic in origin. Studies from our lab and others suggest that host-endogenous small RNAs also play an important role in plant defense in response to other pathogens besides viruses (Katiyar-Agarwal et al., 2006; Navarro et al., 2006). The methods described here provide an opportunity to identify many more novel pathogen-regulated small RNAs in plants, which will help in understanding the regulatory mechanism of plant immunity. Here, we introduce the approaches of powerful high-throughput parallel sequencing and hybridization-based technologies for the discovery and detection of pathogen regulated small RNAs. We mainly compare and discuss the methods of low-molecular weight (LMW) RNA extraction from pathogen-infected tissue and strategies for detecting endogenous small RNAs by Northern blot analysis. PMID- 17720488 TI - Protocols for expression and functional analysis of viral microRNAs. AB - MicroRNAs (miRNAs) are small RNAs of generally 21 to 23 nt that down-regulate target gene expression at the posttranscriptional level. Although miRNAs are endogenously expressed by all animals and plants, numerous DNA viruses have now been identified that also encode miRNAs, presumably to down-modulate protein expression from viral and host transcripts. Although this has been shown in some cases, the function of the majority of viral miRNAs remains unclear. The herpesviruses stand out by making extensive use of miRNA expression during long term latent infection or lytic replication. Because viral miRNAs are only present in the context of viral infection and can therefore be considered "exogenous," their expression in uninfected cells of the appropriate cell type is a valuable tool to assess their function. Techniques to achieve and validate the expression of viral miRNAs are described in this review. PMID- 17720490 TI - Enhanced efficacy in anti-tumour activity by combined therapy of recombinant FGFR 1 related angiogenesis and low-dose cytotoxic agent. AB - Fibroblast growth factor receptor-1 (FGFR-1) has been used as a target for anti angiogeneic therapy of cancer. The strategies of combining anti-angiogenic biotherapy with chemotherapeutic drugs show potential and promise for cancer therapy. In this study, we evaluated the anti-tumour efficacy of chicken FGFR-1 (cFR-1) vaccine combined with low-dose gemcitabine in two mice tumour models. We found that both the cFR-1 vaccine and low-dose gemcitabine can suppress tumour growth to some extent. Remarkably, the combination strategy produces an apparent decrease in tumour volume, microvessel density and tumour cell proliferation, and an increase of apoptosis without obvious side-effects compared with either therapy alone. Moreover, the combination strategy also demonstrated synergistic indices against tumour growth and angiogenesis. Furthermore, auto-antibodies against mouse FGFR-1 were identified. These findings support the idea that the combination strategy synergistically strengthens anti-tumour activity via suppression of tumour angiogenesis without overt toxicity in tumour-bearing mice. PMID- 17720489 TI - Specificity and randomness in the visual cortex. AB - Research on the functional anatomy of visual cortical circuits has recently zoomed in from the macroscopic level to the microscopic. High-resolution functional imaging has revealed that the functional architecture of orientation maps in higher mammals is built with single-cell precision. By contrast, orientation selectivity in rodents is dispersed on visual cortex in a salt-and pepper fashion, despite highly tuned visual responses. Recent studies of synaptic physiology indicate that there are disjoint subnetworks of interconnected cells in the rodent visual cortex. These intermingled subnetworks, described in vitro, may relate to the intermingled ensembles of cells tuned to different orientations, described in vivo. This hypothesis may soon be tested with new anatomic techniques that promise to reveal the detailed wiring diagram of cortical circuits. PMID- 17720491 TI - Dedifferentiated chondrosarcoma: prognostic factors and outcome from a European group. AB - BACKGROUND: Dedifferentiated chondrosarcoma has a very poor prognosis. Because of its rarity, there are few large studies of outcome which might identify potential prognostic factors. In particular there remains uncertainty about the value of chemotherapy for this condition. METHOD: A retrospective study was done using data supplied by members of the European Musculo Skeletal Oncology Society (EMSOS). We obtained data on 337 patients from nine European centres with this rare condition, with details on patients, treatment and outcome which were then analysed in an attempt to identify prognostic features. RESULTS: The median age was 59 years and there was a slight predominance of males (53%). The most common sites were the femur and pelvis. Twenty-nine percent of patients with a long bone tumour had a pathological fracture. 71 patients (21%) had metastases at the time of diagnosis and these patients had a median survival of 5 months with a 10% chance of survival at 2 years. For the 266 patients without metastases at diagnosis, 254 underwent surgery with 79% having limb salvage. Thirty-one percent of these 266 patients had chemotherapy with 47% of those under 60 receiving it. In this group of 266 patients, overall survival was 28% at 10 years and poor prognostic factors were the presence of a pathological fracture at diagnosis, a pelvic location and increasing age. Local recurrence and overall survival were related to inadequate margins of excision. We did not find that the histological subtype, size of the tumour or the use of chemotherapy significantly affected outcome. For all patients the overall survival was 24% at 5 years. CONCLUSIONS: The prognosis for patients with dedifferentiated chondrosarcoma remains dismal. Surgery with clear margins remains the principal treatment for this condition. Further use of chemotherapy should be within a trial or treatment protocol. PMID- 17720492 TI - Capped diaminopropionamide-glycine dipeptides are inhibitors of CC chemokine receptor 2 (CCR2). AB - A new series of CCR2 antagonists has been discovered that incorporates intramolecular hydrogen bonding as a strategy for rigidifying the scaffold. The structure-activity relationship was established through initial systematic modification of substitution pattern and chain length, followed by independent optimization of three different substituents (benzylamine, carboxamide, and benzamide). Several of the acyclic compounds display 10-30 nM binding affinity for CCR2. Moreover, these antagonists are able to block both MCP-1-induced Ca(2+) flux and monocyte chemotaxis, and are selective for binding to CCR2 over CCR1 and CCR3. PMID- 17720493 TI - Structure-activity relationship studies of carboxamido-biaryl ethers as opioid receptor antagonists (OpRAs). Part 1. AB - A structurally unique and new class of opioid receptor antagonists (OpRAs) that bear no structural resemblance with morphine or endogenous opioid peptides has been discovered. A series of carboxamido-biaryl ethers were identified as potent receptor antagonists against mu, kappa and delta opioid receptors. The structure activity relationship indicated para-substituted aryloxyaryl primary carboxamide bearing an amine tether on the distal phenyl ring was optimal for potent in vitro functional antagonism against three opioid receptor subtypes. PMID- 17720494 TI - Novel sulfonamides having dual dopamine D2 and D3 receptor affinity show in vivo antipsychotic efficacy with beneficial cognitive and EPS profile. AB - A novel series of arylsulfonamides was prepared either by automated parallel or by traditional solution-phase synthesis. Several members of this compound library were identified as high-affinity dopamine D3 and D2 receptor ligands. The most interesting representative, compound 2, showed potent antipsychotic behaviour coupled with a beneficial cognitive and EPS profile. PMID- 17720495 TI - Novel anti-tuberculosis agents from MCR libraries. AB - Structure-based design of libraries of multi-component reaction products yields novel potent anti-tuberculosis compounds. Synthesis and preliminary biological results are presented. PMID- 17720496 TI - Mimicking human bipolar ion dysregulation models mania in rats. AB - Psychiatric diseases in general, and bipolar illness in particular, are difficult to model in animals since the subjective nature of the core symptoms appears to preclude objective observation of behavioral changes. An adequate animal model of a psychiatric condition must fulfill three core criteria: share pathophysiological characteristics of the human condition (face validity), have similar behavioral manifestations as the human disease (construct validity), and improve with medications that improve the symptoms seen in afflicted humans (predictive validity). The ouabain model for bipolar illness mimics a widely reproduced biologic abnormality in mania: reduced sodium pump activity. An intracerebroventricular (ICV) administration of 5microL 10(-3)M ouabain induces motoric hyperactivity preventable by lithium, carbamazepine, and haloperidol. ICV ouabain may also produce environmentally dependent hypoactivity. The model, however, has not yet been examined for other potential manic behavior in rats such as reduced need for sleep, increased sexual activity, or increased irritability. While additional characterization of the model is required, the ouabain model for bipolar illness is the only available animal model that fulfills the three criteria for an adequate animal model for bipolar illness. PMID- 17720497 TI - Myasthenia gravis in South Africans: racial differences in clinical manifestations. AB - We present data on the phenotypic variation in myasthenia gravis of 205 subjects from a multi-racial South African cohort. Consecutive subjects seen more than twice from 1996 to 2006, were included. Documented observational data included a myasthenia gravis and extra-ocular eye muscle score. Results showed Black subjects were more likely than Whites to develop treatment-resistant complete ophthalmoplegia and ptosis (18% vs. 2%; p=0.041). Of the 14 patients with this phenotype, 13 had generalised disease and positive AChR antibodies. Despite similar sized cohorts, White subjects were more likely than Blacks to develop generalised myasthenia poorly responsive to therapy (p=0.005). There were no significant racial differences in the time between diagnosis to initiation of therapy, or the performance and timing of thymectomy. The racial variation in some phenotypic features of myasthenia gravis and outcome to therapy, highlights the need to study biological factors in different subgroups to develop a more rational approach to immuno-suppressive therapy. PMID- 17720498 TI - Ataxia-oculomotor apraxia 2 patients show no increased sensitivity to ionizing radiation. AB - Mutations in senataxin have been described recently in 24 cases of French Canadian descent with ataxia-oculomotor apraxia 2. This recessive ataxia is associated with an elevation in alpha-fetoprotein as in ataxia-telangiectasia. Because ataxia-telangiectasia cells are highly radiosensitive, we used a colony survival assay to measure the radiosensitivity of lymphoblastoid cell lines derived from five French-Canadian patients with ataxia-oculomotor apraxia 2. Two were homozygous for the common French-Canadian L1976R SETX missense mutation; the three others were compound heterozygotes for the common mutation and three different missense mutations. Overall, lymphoblastoid cell lines derived from these cases did not show significant variation from a normal response to 1 Gray of ionizing radiation but the two patients who were homozygous for the common L1976R mutation fell in the intermediate or non-diagnostic range. PMID- 17720499 TI - Behavior patterns in Duchenne muscular dystrophy: report on the Parent Project Muscular Dystrophy behavior workshop 8-9 of December 2006, Philadelphia, USA. PMID- 17720500 TI - The acceptance and feasibility of breast cancer screening in the East. AB - Breast cancer, traditionally a disease prevalent among women in the West, has become an increasing disease burden in the East. In Hong Kong, breast cancer is the number one incident cancer in women. In Asian countries, due to the lower incidence rate, population screening is still controversial. Most screening programs are not population-based, and are either self-financed privately or partially subsidized by the government. Since the first government-subsidized screening program was set up in 1991 in Hong Kong, numerous private and government health centres for women have been set up. A dedicated private Breast Care Centre was set up at the Hong Kong Sanatorium and Hospital (HKSH) in 1999. Over an 8-year period from October 1999 to September 2006, 14,596 women were screened, of whom 11,408 were asymptomatic. This study aims to produce the first report on breast screening experience in the largest cohort of asymptomatic Chinese women in the private sector. An overall malignancy detection rate of 2.3 per 1000 screens and a recall rate of 9.2% were found. Despite culture differences and differences in breast characteristics (denser and smaller breasts), breast screening is feasible and acceptable in the East. PMID- 17720501 TI - Using specific cytotoxics with a targeted mind. AB - It is largely known that clinical activity of a given cytotoxic agent may vary between different patients. This suggests that breast cancer sub-types can be identified within the endocrine-resistant cohort, each of them with a specific degree of sensitivity to different cytotoxic drugs. Pre-clinical and early clinical data suggest that in the future some molecular markers might have practical value in predicting cytotoxics activity in the clinical setting. The most relevant evidence is summarized below according to the type of cytotoxic agent: (a) Anthracyclines Topoisomerase II alpha (topo II) gene aberrations (amplification or deletion) and/or topo II protein overexpression seem to predict response to topo II inhibitors such as anthracyclines. Of note, HER-2 amplified tumors have a concomitant topo II gene aberration in approximately 50% of cases. Moreover, the majority of hyper-proliferating tumors carry topo II protein overexpression. Early clinical data suggest the existence of a direct correlation between anthracyclines activity and the presence of topo II gene aberration or topo II protein overexpression. (b) Taxanes Microtubule-associated parameters (MTAP) such as the TAU protein, HER-2 gene amplification, and p-53 gene mutations, have been suggested as potential predictive markers for taxanes. Although early clinical data support pre-clinical experiments, the lack of large prospectively designed clinical studies makes it difficult to draw conclusions on the predictive value of these molecular markers. (c) DNA-damaging agents The BRCA 1 protein seems to play a major role in activating DNA repair mechanisms. Loss-of function BRCA 1 mutations might lead to a substantial deficit in DNA repair mechanisms. This could ultimately translate into increased tumor sensitivity to DNA-damaging agents such as alkylating compounds and platinum-derivates. Pre clinical and early clinical data seem to suggest that some BRCA 1 gene mutations might render the tumor more sensitive to DNA-damaging agents and clinical studies have recently been activated to investigate properly this hypothesis. A new generation of ongoing clinical studies and a "focused" use of the gene micro array technology will hopefully clarify the complex interaction existing between molecular targets and cytotoxic drug activity. This "targeted" approach to chemotherapy might ultimately lead to a more effective strategy in breast cancer medical treatment. PMID- 17720502 TI - Adjuvant therapy and thrombosis: how to avoid the problem? AB - The occurrence of thrombosis complicates the management of breast cancer because of the need for anticoagulant therapy. The pathogenesis of venous thrombosis in breast cancer is related to Virchow's triad: venous stasis, hypercoagulability related to procoagulants and vessel wall injury secondary to chemotherapy and indwelling catheters. The rate of thrombosis with tamoxifen is approximately 0.9%. There does not appear to be an increased risk of venous thrombosis with aromatase inhibitors. The thrombotic rates in patients with early stage breast cancer receiving adjuvant chemotherapy range from 3% to 8%. Thrombotic rates are higher in post-menopausal women receiving adjuvant chemotherapy and in women receiving tamoxifen in combination with chemotherapy. Thrombosis can be reduced by avoiding chemotherapy in situations where its potential efficacy is marginal. In the future, new targeted agents may avoid thrombotic complications and a number of new antithrombotic agents which are oral and do not require laboratory monitoring could be used by oncologists to prevent thrombosis. PMID- 17720503 TI - Organisation, strengths and difficulties of South African intensive care nursing. PMID- 17720504 TI - Risk factors for pathologic gambling and other compulsions among Parkinson's disease patients taking dopamine agonists. AB - Three hundred patients with Parkinson's disease taking dopamine agonists were surveyed for the presence of compulsions. Fifty-eight reported active compulsions which had developed after initiation of dopamine agonists. These included 25 with sexual compulsions and 28 with self-described compulsive gambling, of whom 17 met criteria for pathologic gambling. Males were over-represented. Patients with any compulsion and those with pathologic gambling were about 6 years younger than those without compulsions. These behavioral problems were not associated with an individual dopamine agonist, nor dose or duration, nor concomitant levodopa. Follow-up of the pathologic gamblers 1 year after intervention, which was cessation of the dopamine agonist in most cases, found ongoing but controlled gambling in five and complete cessation within 4 months in the remainder. PMID- 17720505 TI - Application of commercial glasses for high dose measurement using the thermoluminescent technique. AB - Commercial glasses under this study showed linear thermoluminescence (TL) response in gamma dose range 100 Gy to 10 kGy, glow peaks between 175 and 200 degrees C, fading under dark and room light 2.86-7.36% and 10.42-20.82%, respectively, in 24h and 34.86-70.80% under sunlight in 5h after exposure. The TL glass dosimetric results have been found to be reproducible within +/- 6.0%. Glasses have been observed as thermally unstable and its TL sensitivity reduces after annealing. The TL response of the glasses has been found to reduce by 7.40 51.49% after first annealing of the samples at 400 degrees C for 15 min. The trace element study suggests that presence of impurities has no role in TL sensitivity of glasses rather imperfections and dislocations in the lattice are the major contributor in the formation of TL centers. Commercial glasses can serve as good TL material for gamma irradiator and gamma chamber dosimetry. The various radiation parameters for glass TL dosimetry have been studied in detail and presented. PMID- 17720506 TI - Anti-ganglioside antibodies alter presynaptic release and calcium influx. AB - Acute motor axonal neuropathy (AMAN) variant of Guillain-Barre syndrome is often associated with IgG anti-GM1 and -GD1a antibodies. The pathophysiological basis of antibody-mediated selective motor nerve dysfunction remains unclear. We investigated the effects of IgG anti-GM1 and -GD1a monoclonal antibodies (mAbs) on neuromuscular transmission and calcium influx in hemidiaphragm preparations and in cultured neurons, respectively, to elucidate mechanisms of Ab-mediated muscle weakness. Anti-GM1 and -GD1a mAbs depressed evoked quantal release to a significant yet different extent, without affecting postsynaptic currents. At equivalent concentrations, anti-GD1b, -GT1b, or sham mAbs did not affect neuromuscular transmission. At fourfold higher concentration, an anti-GD1b mAb (specificity described in immune sensory neuropathies) induced completely reversible blockade. In neuronal cultures, anti-GM1 and -GD1a mAbs significantly reduced depolarization-induced calcium influx. In conclusion, different anti ganglioside mAbs induce distinct effects on presynaptic transmitter release by reducing calcium influx, suggesting that this is one mechanism of antibody mediated muscle weakness in AMAN. PMID- 17720508 TI - Changes in cerebral blood volume and amyloid pathology in aged Alzheimer APP/PS1 mice on a docosahexaenoic acid (DHA) diet or cholesterol enriched Typical Western Diet (TWD). AB - High dietary cholesterol and low dietary docosahexaenoic acid (DHA) intake are risk factors for Alzheimer's disease (AD). However, it is unclear how these components influence the course of the disease. We investigated the effects of dietary lipids on beta-amyloid deposition and blood circulation in the brains of 18-month-old APP/PS1 mice. Starting at 6 months of age, mice were fed a regular rodent chow, a Typical Western Diet (TWD) containing 1% cholesterol, or a diet with a high (0.5%) level of DHA for 12 months. Relative cerebral blood volume (rCBV) and flow (CBF) were determined with (2)H MR spectroscopy and gradient echo contrast enhanced MRI. Deposition of beta-amyloid was visualized in fixed brain tissue with immunohistochemistry. The TWD diet increased plaque burden in the dentate gyrus of the hippocampus, but did not significantly reduce rCBV. In contrast, the DHA-enriched diet increased rCBV without changing blood flow indicating a larger circulation in the brain probably due to vasodilatation and decreased the amount of vascular beta-amyloid deposition. Together, our results indicate that the long-term intake of dietary lipids can impact both brain circulation and beta-amyloid deposition, and support the involvement of hemodynamic changes in the development of AD. PMID- 17720507 TI - Behavioral and electrophysiological effects of the adenosine A2A receptor antagonist SCH 58261 in R6/2 Huntington's disease mice. AB - The effect of chronic treatment with the selective adenosine A2A receptor antagonist SCH 58261 on the behavioral and electrophysiological alterations typical of R6/2 mice (a transgenic mouse model of Huntington's disease, HD), has been studied. Starting from 5 weeks of age, R6/2 and wild type (WT) mice were treated daily with SCH 58261 (0.01 mg/kg i.p.) for 7 days. In the following weeks, the ability of mice to perform in the rotarod, plus maze and open field tests were evaluated. In addition, with electrophysiological experiments in corticostriatal slices we tested whether the well-known increased NMDA vulnerability of R6/2 mice was prevented by SCH 58261 treatment. We found that chronic treatment with SCH 58262: i) fully prevented the alterations in emotional/anxious responses displayed by R6/2 mice; ii) did not prevent the impairment in motor coordination; iii) abolished the increase in NMDA-induced toxicity observed in the striatum of HD mice. On balance, targeting A2A receptors seems to have some beneficial effects in HD even though, given the complexity of A2A receptor pharmacology and HD pathogenesis, further studies are necessary to clarify whether A2A receptor antagonists have therapeutic potential in HD. PMID- 17720509 TI - Responses of epidermal phenolic compounds to light acclimation: in vivo qualitative and quantitative assessment using chlorophyll fluorescence excitation spectra in leaves of three woody species. AB - Chlorophyll fluorescence (ChlF) excitation spectra were measured to assess the UV sunscreen compounds accumulated in fully expanded leaves of three woody species belonging to different chemotaxons, (i.e. Morus nigra L., Prunus mahaleb L. and Lagerstroemia indica L.), grown in different light microclimates. The logarithm of the ratio of ChlF excitation spectra (logFER) between two leaves acclimated to different light microclimates was used to assess the difference in epidermal absorbance (EAbs). EAbs increased with increasing solar irradiance intercepted for the three species. This epidermal localisation of UV-absorbers was confirmed by the removal of the epidermis. It was possible to simulate EAbs as a linear combination of major phenolic compounds (Phen) identified in leaf methanol extracts by HPLC-DAD. Under UV-free radiation conditions, shaded leaves of M. nigra accumulated chlorogenic acid. Hydroxybenzoic acid (HBA) derivatives and hydroxycinnamic acid (HCA) derivatives greatly increased with increasing PAR irradiance under the low UV-B conditions found in the greenhouse. These traits were also observed for the HCA of the two other species. Flavonoid (FLAV) accumulation started under low UV-A irradiance, and became maximal in the adaxial epidermis of sun-exposed leaves outdoors. A decrease in the amount of HCA was observed concomitantly to the intense accumulation of FLAV for both leaf sides of the three species. Judging from the logFER, under low UV-B conditions, larger amounts of HCA are present in the epidermis in comparison to FLAV for the three species. Upon transition from the greenhouse to full sunlight outdoors, there was a decrease in leaf-soluble HCA that paralleled FLAV accumulation in reaction to increasing solar UV-B radiation in the three species. In M. nigra, that contains large amounts of HCA, the logFER analysis showed that this decrease occurred in the adaxial epidermis, whereas the abaxial epidermis, which is protected from direct UV-B radiation, continued to accumulate large amounts of HCA. PMID- 17720510 TI - Anticoagulation for chronic atrial fibrillation in hemodialysis patients: which fruit from the decision tree? PMID- 17720512 TI - Dialysis facility ownership and epoetin dosing in hemodialysis patients: a US physician perspective. PMID- 17720511 TI - Dialysis facility ownership and epoetin dosing in hemodialysis patients: an overview. PMID- 17720513 TI - Dialysis facility ownership and epoetin dosing in hemodialysis patients: a view from Europe. PMID- 17720514 TI - Dialysis facility ownership and epoetin dosing in hemodialysis patients: a medical economic perspective. PMID- 17720515 TI - Dialysis facility ownership and epoetin dosing in hemodialysis patients: a dialysis provider's perspective. PMID- 17720516 TI - Is there a role for intensive insulin therapy in patients with kidney disease? AB - There is increasing evidence for the benefit of intensive insulin therapy in maintaining near-normoglycemia in patients without diabetes with severe acute illness. Morbidity and mortality have both improved, with decreased episodes of sepsis, acute kidney injury, transfusion requirements, and post-intensive care complications. The metabolic mayhem of severe acute illness has many parallels with those induced by kidney failure itself, and patients with kidney failure are at increased risk from many of the complications potentially improved by insulin therapy. We reviewed the potential benefits of intensive insulin therapy and examined the published trials for data directly applicable to patients with kidney failure. There are no trials directly answering the question and no specific analysis of patients with kidney disease in published studies. We extracted pertinent data regarding patients with impaired renal function from the reported trials, identified parallels between patients with kidney injury and other severe illnesses, and suggest possible future studies. We hypothesize that intensive insulin therapy has a role outside the intensive care setting and, in particular, a role for patients with severe acute illness and kidney failure, whether acute or chronic. PMID- 17720517 TI - Balancing Fistula First with Catheters Last. AB - The success of Fistula First nationwide has been accompanied by an unplanned increase in hemodialysis catheters. Complications related to prolonged hemodialysis catheter use include increased morbidity, mortality, and cost. We hypothesize that the national focus on increasing fistulas may have inadvertently diverted attention away from initiatives to decrease dependence on hemodialysis catheters. Based on a synthesis of guidelines, reviews, published evidence, and the authors' opinions, we propose that the national vascular access initiative be revised to have a dual goal of Fistula First and "Catheters Last." These goals are not mutually exclusive, but rather complementary. We recommend a systematic refocus on interventions that not only increase fistulas, but help avoid extended catheter use. Clearly, the ideal practice for hemodialysis vascular access remains early placement of fistulas with enough maturation time such that they can be used for initiating long-term hemodialysis therapy when the need arises. To effect this change, a reimbursement policy covering the costs associated with permanent access placement before the need for dialysis is essential. Individualized patient management strategies may consider such innovative approaches as initiating patients on peritoneal dialysis therapy or using nonautogenous grafts as bridge accesses in lieu of catheters. For patients who are dialyzing using catheters, immediate active planning for permanent access placement and removal of the catheter is necessary. In the same vein as Fistula First, the renal community should once again be galvanized in working together toward controlling the catheter epidemic in our dialysis population. PMID- 17720518 TI - Long-term risk of cancer in membranous nephropathy patients. AB - BACKGROUND: There is a well-known association between membranous nephropathy (MN) and cancer, and patients with MN usually are examined for cancer at the time of diagnosis. The long-term risk of cancer after MN is not well studied. STUDY DESIGN: Cohort study with record linkage between the Norwegian Kidney Biopsy Registry and Norwegian Cancer Registry. SETTING & PARTICIPANTS: 161 patients with MN from 1988 to 2003. PREDICTOR: Patients with MN compared with the age- and sex adjusted general Norwegian population. OUTCOMES: Cancer diagnosis reported through 2003. RESULTS: Mean duration of follow-up was 6.2 years (range, 0.1 to 15 years). 33 patients developed cancer; including 24 patients with cancer after the diagnosis of MN. Median time from diagnosis of MN to diagnosis of cancer was 60 months (range, 0 to 157 months). Mean annual incidence ratio of cancer was 2.4/100 person-years (2.1/100 person-years in the 0- to 5-year period and 2.8/100 person-years for the 5 to 15 years after kidney biopsy). During the 0 to 15 years after the diagnosis of MN, the expected number of cancers was 10.7, resulting in a standardized incidence ratio of cancer of 2.25 (95% confidence interval, 1.44 to 3.35). In the 5 to 15 years after diagnosis, standardized incidence ratio was 2.30 (95% confidence interval, 1.19 to 4.02). Patients with MN who developed cancer were older (65 versus 52 years; P < 0.001). Patients with cancer and MN had a greater mortality rate than patients without cancer (67% versus 26%; P < 0.001). LIMITATIONS: Follow-up treatment after MN with cytotoxic and immunosuppressive medications is not known. CONCLUSIONS: An increased risk of developing cancer is observed after the diagnosis of MN, which persists for many years. PMID- 17720519 TI - Body mass index and mortality in CKD. AB - BACKGROUND: Greater body mass index (BMI) is associated with worse survival in the general population, but appears to confer a survival advantage in patients with kidney failure treated by hemodialysis. Data are limited on the relationship of BMI with mortality in patients in the earlier stages of chronic kidney disease (CKD). STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: The Modification of Diet in Renal Disease (MDRD) Study examined the effects of dietary protein restriction and blood pressure control on progression of kidney disease. This analysis includes 1,759 subjects. PREDICTOR: BMI. OUTCOMES & MEASUREMENTS: Cox models were used to evaluate the relationship of quartiles of BMI with all-cause and cardiovascular disease (CVD) mortality. RESULTS: Mean GFR and BMI were 39 +/- 21 (SD) mL/min/1.73 m(2) and 27.1 +/- 4.7 kg/m(2), respectively. During a mean follow-up of 10 years, there were 453 deaths (26%), including 272 deaths (16%) from CVD. In unadjusted Cox models, quartiles 3 (hazard ratio [HR], 1.45; 95% confidence interval [CI], 1.11 to 1.90) and 4 (HR, 1.58; 95% CI, 1.21 to 2.06) were associated with increased risk of all-cause mortality compared with quartile 1. Adjustment for demographic, CVD, and kidney disease risk factors and randomization status attenuated this relationship for quartiles 3 (HR, 0.81; 95% CI, 0.60 to 1.09) and 4 (HR, 0.83; 95% CI, 0.61 to 1.20). In unadjusted Cox models, quartiles 3 (HR, 1.66; 95% CI, 1.17 to 2.36) and 4 (HR, 1.63; 95% CI, 1.15 to 2.33) were associated with increased risk of CVD mortality. Multivariable adjustment attenuated this relationship for quartiles 3 (HR, 0.92; 95% CI, 0.63 to 1.36) and 4 (HR, 0.85; 95% CI, 0.57 to 1.27). LIMITATIONS: Primary analyses were based on single measurement of BMI. Because the MDRD Study cohort included relatively young white subjects with predominantly nondiabetic CKD, results may not be generalizable to all patients with CKD. CONCLUSIONS: In this cohort of subjects with predominantly nondiabetic CKD, BMI does not appear to be an independent predictor of all-cause or CVD mortality. PMID- 17720520 TI - Kidney function and aortic valve and mitral annular calcification in the Multi Ethnic Study of Atherosclerosis (MESA). AB - BACKGROUND: Aortic valve calcification (AVC) and mitral annular calcification (MAC) are highly prevalent and predictive of mortality in end-stage renal disease populations. Whether less severe kidney dysfunction is associated with AVC and MAC is uncertain. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: Ethnically diverse middle-aged adults without clinically apparent cardiovascular disease who participated in the Multi-Ethnic Study of Atherosclerosis. PREDICTOR: Estimated glomerular filtration rate (eGFR), cystatin C, and microalbuminuria. OUTCOMES & MEASUREMENTS: AVC and MAC were determined by means of computed tomography. Multivariable logistic regression evaluated the association of kidney function with AVC and MAC. RESULTS: Of 6,785 participants, 10% had an eGFR less than 60 mL/min/1.73 m(2) (<1.0 mL/s/1.73 m(2)), mean cystatin C level was 0.9 +/- 0.2 mg/L, 7% had microalbuminuria (albumin >or= 30 mg/g), 15% had diabetes, 13% had AVC, and 9% had MAC. In adjusted analyses for AVC, eGFR less than 60 mL/min/1.73 m(2) (adjusted odds ratio, 1.23; 95% confidence interval, 0.99 to 1.14) and greater cystatin C concentrations (per SD increase; adjusted odds ratio, 1.06; 95% confidence interval, 0.99 to 1.14) had modest associations. Microalbuminuria was not associated independently with AVC (adjusted odds ratio, 1.11; 95% confidence interval, 0.89 to 1.40). For the MAC end point, associations of eGFR less than 60 mL/min/1.73 m(2) and greater cystatin C level differed by diabetes status (P for interaction = 0.1 and 0.02, respectively). In persons with diabetes, eGFR less than 60 mL/min/1.73 m(2) (adjusted odds ratio, 2.03; 95% confidence interval, 1.26 to 3.25) and greater cystatin C level (adjusted odds ratio, 1.38; 95% confidence interval, 1.14 to 1.68) were associated strongly, whereas no association was observed in subjects without diabetes (eGFR < 60 mL/min/1.73 m(2): adjusted odds ratio, 1.13; 95% confidence interval, 0.86 to 1.49; cystatin C: adjusted odds ratio, 1.03; 95% confidence interval, 0.93 to 1.13). The association of microalbuminuria with MAC (adjusted odds ratio, 1.37; 95% confidence interval, 1.06 to 1.76) did not differ by diabetes status (P for interaction = 0.2). LIMITATIONS: There were few participants with severe kidney disease. CONCLUSIONS: Impaired kidney function had only a modest association with AVC, whereas its association with MAC was observed only in persons with diabetes. Future studies should evaluate whether associations of kidney impairment with dystrophic calcification differ by diabetes status in other clinical settings and vascular beds. PMID- 17720521 TI - Should hemodialysis patients with atrial fibrillation undergo systemic anticoagulation? A cost-utility analysis. AB - BACKGROUND: Approximately 14% of hemodialysis patients have atrial fibrillation. Hemodialysis patients with atrial fibrillation appear to be at increased risk of both thromboembolic complications and bleeding. Furthermore, there is uncertainty regarding the efficacy of warfarin or acetylsalicylic acid (ASA) therapy for preventing strokes in this subgroup because they were excluded from relevant trials. STUDY DESIGN: We performed a cost-utility analysis. Probabilistic sensitivity analysis was used to incorporate parameter uncertainty into the model. Expected value of perfect information and scenario analyses were performed to identify the important drivers of the decision and focus future research. SETTING & POPULATION: Base case was a 60-year-old male hemodialysis patient in the United States. MODEL, PERSPECTIVE, & TIME FRAME: A Markov Monte Carlo microsimulation model was constructed from the perspective of the health care payer, and patients were followed up during their lifetime. INTERVENTION: We compared 3 alternative treatment strategies for permanent atrial fibrillation in hemodialysis patients: warfarin, ASA, or no treatment. OUTCOMES: Quality-adjusted survival and cost. RESULTS: ASA and warfarin both prolonged survival compared with no treatment (0.06 and 0.15 quality-adjusted life-years [QALYs], respectively). ASA was associated with an incremental cost-effectiveness ratio of $82,100/QALY. Warfarin provided additional benefits at a cost of $88,400 for each QALY gained relative to ASA. At a threshold of $100,000/QALY, the probabilities that no treatment, warfarin, and ASA were the most efficient therapy were 20%, 58%, and 23%, respectively. LIMITATIONS: Parameterization data and costs were taken from US studies and may not be generalizable to other countries. Peritoneal dialysis patients were not included in the analysis. CONCLUSIONS: The high future cost of hemodialysis constrains incremental cost-effectiveness ratios to values greater than commonly cited thresholds ($50,000/QALY). Based on available evidence, warfarin appears to be the optimal therapy to prevent thromboembolic stroke in hemodialysis patients with atrial fibrillation. Additional study is required to determine the efficacy of warfarin and risk of bleeding complications in this population so that patients can make a more informed choice. PMID- 17720522 TI - Warfarin anticoagulation in hemodialysis patients: a systematic review of bleeding rates. AB - BACKGROUND: Despite common use of warfarin, the bleeding risk associated with this treatment in hemodialysis (HD) patients is unknown. STUDY DESIGN: Systematic review. SELECTION CRITERIA FOR STUDIES: Inclusion criteria were case series, cohort studies, and randomized controlled trials in dialysis patients that examined the bleeding risk associated with warfarin use compared with no warfarin or subcutaneous heparin. Studies with fewer than 10 subjects, case reports, abstracts lacking complete data sets, review articles, and editorials were excluded. PREDICTOR: Warfarin use compared with no warfarin or subcutaneous heparin. OUTCOMES: Data for bleeding were reported as rates: number of bleeding episodes per number of patient-years of warfarin exposure or follow-up. RESULTS: Of 79 articles and abstracts, 5 met inclusion criteria and 3 more could be added after investigators provided additional information. All studies were of HD patients, and 7 of 8 evaluated the use of warfarin for the prevention of HD access thrombosis. Intensity of anticoagulation varied. Meta-analysis was not possible because of study heterogeneity. Studies of full-intensity anticoagulation and the 1 randomized controlled trial of low-intensity anticoagulation showed major bleeding episode rates ranging from 0.1 to 0.54 events/patient-year of warfarin exposure. These rates are approximately twice as high as those of HD patients receiving either no warfarin or subcutaneous heparin. LIMITATIONS: This review is based largely on data from observational studies in which bleeding rates may be confounded by comorbidity. Relatively small sample sizes may provide imprecise estimates of rates. CONCLUSION: Low- and full-intensity anticoagulation use in HD patients is associated with a significant bleeding risk, which has to be balanced against any potential benefit of therapy. This has to be considered carefully when prescribing warfarin to HD patients. PMID- 17720523 TI - Bone alterations in children and young adults with renal transplant assessed by phalangeal quantitative ultrasound. AB - BACKGROUND: Bone alterations in young renal transplant recipients were investigated in several studies with conflicting results. Quantitative ultrasound of the phalanges is a recently developed noninvasive procedure to assess skeletal status. STUDY DESIGN: Cross-sectional study at a single transplant center with values compared with previously studied healthy controls. SETTINGS & PARTICIPANTS: 40 children and young adult recipients of renal grafts (15 females, 25 males; age, 20.0 +/- 8.4 years) studied 7.1 +/- 3.8 years after kidney transplantation. PREDICTOR: Clinical, biochemical, and therapeutic features, including calcium, phosphate, and intact parathormone levels; and cumulative dosages of glucocorticoids and cyclosporine administered since transplantation. OUTCOME & MEASUREMENT: Phalangeal quantitative ultrasound, including amplitude dependent speed of sound (AD-SoS) and bone transmission time (BTT), mainly dependent on mineral density and cortical thickness, respectively. Age- and sex matched healthy controls were used to provide age-related z scores; sex- and height-matched healthy subjects, to provide z scores related to statural age. RESULTS: Mean z scores of AD-SoS and BTT were -0.05 +/- 1.59 and -0.54 +/- 1.17, respectively (P > 0.05 and P < 0.001, respectively). Multivariate analysis showed that AD-SoS z score was associated significantly with body mass index, intact parathormone level, cumulative glucocorticoids administered in the first posttransplantation year, and cyclosporine administered since transplantation (model r(2) = 0.79; P < 0.001); BTT z score was associated significantly with glucocorticoid dosage in the first posttransplantation year and age (model r(2) = 0.55; P < 0.001). LIMITATIONS: Absence of other measures of bone structure and longitudinal measures and comparison to a noncurrent control group. CONCLUSIONS: Children and young adults may have decreased cortical thickness with maintained overall mineral density after renal transplantation. The findings of phalangeal quantitative ultrasound parallel observations using other imaging techniques. Phalangeal quantitative ultrasound may be a useful method to assess bone alternations after renal transplantation. PMID- 17720524 TI - Obesity and hemodialysis vascular access failure. AB - A variety of factors have been proposed to explain arteriovenous fistula primary failures in patients undergoing hemodialysis, including obesity, diabetes mellitus, female sex, and the absence of preoperative vein mapping. In this report, we describe 2 women for whom premature upper-extremity arteriovenous fistula failures occurred in the setting of venographic evidence of soft-tissue compression of the venous outflow with the patient's arm in the adducted position. In each instance, preoperative noninvasive duplex vein mapping showed veins of adequate diameter (0.28 to 0.54 cm), and further evaluation showed no evidence of a hypercoagulable state. Upper-extremity venography was used to assess central venous patency and fully assess the venous vasculature. Unlike the widely patent venous systems seen in the abducted position, venography performed with the upper extremities in adduction showed marked narrowing of the brachial and/or axillary veins. The hemodynamic effects of this narrowing were readily apparent in patient 2 with the appearance of collateral filling of the cephalic vein in the adducted position. Patient 1 had a body mass index of 39 kg/m(2), and patient 2 had a body mass index of 34 kg/m(2). Each patient had excess axillary soft tissue that appeared to compress the venous outflow in adduction. To our knowledge, this is the first report to radiographically document soft-tissue compression of the venous outflow of the upper extremity in the adducted position, suggesting a mechanism whereby obesity, or at least excess axillary fat, can lead to premature hemodialysis vascular access failures. PMID- 17720525 TI - Tubulointerstitial nephritis associated with IgG4-related autoimmune disease. AB - Autoimmune pancreatitis is a chronic fibroinflammatory condition primarily affecting the pancreas. Recent accumulating evidence suggested that autoimmune pancreatitis is a systemic autoimmune disease (immunoglobulin G4 [IgG4]-related autoimmune disease) affecting various organs with dense infiltration of IgG4 positive mononuclear cells. Tubulointerstitial nephritis is still a mysterious disease with an unknown cause. We report 2 cases of tubulointerstitial nephritis associated with autoimmune pancreatitis. In these patients, dense infiltrations of IgG4-positive mononuclear cells were observed in renal interstitium, with high serum IgG4 levels. Furthermore, in patient 1, who had sclerosing cholangitis, serum alkaline phosphatase and serum creatinine levels changed synchronously. Steroid therapy was followed by improved renal function and serum IgG4 levels in both patients. Because tubulointerstitial nephritis associated with IgG4-related autoimmune disease shows a favorable response to steroids and the renal dysfunction and pancreatic dysfunction are reversible, awareness of this entity is necessary for early diagnosis and prompt treatment. In addition, these cases support the hypothesis that IgG4-related autoimmune disease could be one cause of tubulointerstitial nephritis. PMID- 17720526 TI - Salicylate-induced proximal tubular dysfunction. AB - We describe the case of a 17-year-old girl who was admitted to our clinic for drug poisoning. Twelve hours after the ingestion of 25 tablets of aspirin (12.5 g of acetylsalicylic acid), the patient had a generalized proximal tubular dysfunction characterized by glucosuria (in the face of normal serum glucose levels), proteinuria, and uric acid wasting. Further characterization of the tubular dysfunction using high-resolution proton nuclear magnetic resonance spectroscopy of the urine showed a pattern consistent with proximal tubular injury. An important characteristic of the salicylate-induced proximal tubular dysfunction in our patient was its rapid reversibility. A trend toward normalization of fractional excretion values of electrolytes was observed 2 days after ingestion. Determination of serum and urine metabolites and spectroscopy of urine 15 days later showed no evidence of tubular dysfunction. The mechanisms potentially implicated in the pathogenesis of salicylate-induced Fanconi syndrome are discussed and a brief review of the relevant literature is provided. PMID- 17720527 TI - Acute crescentic glomerulonephritis in a renal allograft: an unusual complication of fungal infection. PMID- 17720528 TI - KDOQI Clinical Practice Guideline and Clinical Practice Recommendations for anemia in chronic kidney disease: 2007 update of hemoglobin target. PMID- 17720529 TI - Protein desolvation in UV matrix-assisted laser desorption/ionization (MALDI). AB - We describe experiments in MALDI-TOF and MALDI-TOF-TOF showing that the ejection of protein-matrix cluster ions and their partial decay in the source occur in MALDI. The use of radial beam deflection and small size detector in linear mode allows detection of ions with higher time-of-flight and kinetic energy deficit. MALDI-TOF-TOF experiments were carried out by selecting chemical noise ions at m/z higher than that of a free peptide ion. Whatever the selected m/z (up to m/z 300) the molecular peptide ion appeared as the main fragment. The production of protein-matrix clusters and their partial decay in the source was found to increase with the size of the protein (MW from 1000 to 150,000 u), although it decreases with increasing charge state. These effects were observed for different matrices (HCCA and SA) and in a large laser fluence range. Experimental results and calculation highlight that a continuous decay of protein-matrix cluster ions occurs in the source. This decay-desolvation process can account for the high mass tailing and peak shifting as well as the strong noise/background in the mass spectra of proteins. PMID- 17720530 TI - Chromatographic alignment of LC-MS and LC-MS/MS datasets by genetic algorithm feature extraction. AB - Liquid chromatography-mass spectrometry (LC-MS) datasets can be compared or combined following chromatographic alignment. Here we describe a simple solution to the specific problem of aligning one LC-MS dataset and one LC-MS/MS dataset, acquired on separate instruments from an enzymatic digest of a protein mixture, using feature extraction and a genetic algorithm. First, the LC-MS dataset is searched within a few ppm of the calculated theoretical masses of peptides confidently identified by LC-MS/MS. A piecewise linear function is then fitted to these matched peptides using a genetic algorithm with a fitness function that is insensitive to incorrect matches but sufficiently flexible to adapt to the discrete shifts common when comparing LC datasets. We demonstrate the utility of this method by aligning ion trap LC-MS/MS data with accurate LC-MS data from an FTICR mass spectrometer and show how hybrid datasets can improve peptide and protein identification by combining the speed of the ion trap with the mass accuracy of the FTICR, similar to using a hybrid ion trap-FTICR instrument. We also show that the high resolving power of FTICR can improve precision and linear dynamic range in quantitative proteomics. The alignment software, msalign, is freely available as open source. PMID- 17720531 TI - Algorithm for processing raw mass spectrometric data to identify and quantitate complex lipid molecular species in mixtures by data-dependent scanning and fragment ion database searching. AB - We developed the Lipid Qualitative/Quantitative Analysis (LipidQA) software platform to identify and quantitate complex lipid molecular species in biological mixtures. LipidQA can process raw electronic data files from the TSQ-7000 triple stage quadrupole and LTQ linear ion trap mass spectrometers from Thermo-Finnigan and the Q-TOF hybrid quadrupole/time-of-flight instrument from Waters-Micromass and could readily be modified to accommodate data from others. The program processes multiple spectra in a few seconds and includes a deisotoping algorithm that increases the accuracy of structural identification and quantitation. Identification is achieved by comparing MS(2) spectra obtained in a data dependent manner to a library of reference spectra of complex lipids that we have acquired or constructed from established fragmentation rules. The current form of the algorithm can process data acquired in negative or positive ion mode for glycerophospholipid species of all major head-group classes. PMID- 17720532 TI - Dyrk1A overexpression in immortalized hippocampal cells produces the neuropathological features of Down syndrome. AB - Down syndrome (DS) is the most common genetic disorder, characterized by mental retardation, congenital heart abnormalities, and susceptibility to Alzheimer's disease (AD). Brain development of DS patients is associated with elevated apoptosis and abnormal neuronal differentiation. Those key features are closely associated with many genes mapped within Down syndrome critical region (DSCR) on human chromosome 21. Proline-directed serine/threonine kinase, Dyrk1A, is mapped within DSCR, and involved in the control of cell growth and postembryonic neurogenesis. Despite the potential involvement of Dyrk1A in neurodegeneration, its links to AD susceptibility and the neuropathology of DS patients are not yet clearly understood. Here, we report evidence supporting the correlation between Dyrk1A and neuropathology of DS. Our results show that Dyrk1A interacts with and directly phosphorylates tau and amyloid precursor protein in immortalized hippocampal progenitor H19-7 cells. In addition, the formation of tau inclusion and the enhanced generation of beta-amyloid fragment were detected in H19-7 cells that overexpressed Dyrk1A. Furthermore, these cells show a marked increase in apoptotic cell death under conditions of serum deprivation and also exhibit defects in neuronal differentiation. These results suggest that up-regulation of Dyrk1A may cause AD-like pathogenesis and abnormal neurobiological features in DS patients. PMID- 17720533 TI - Nociceptors of dorsal root ganglion express proton-sensing G-protein-coupled receptors. AB - One major goal in pain research is to identify novel pain targets. Tissue injury, inflammation, and ischemia are usually accompanied by local tissue acidosis, the degree of associated pain or discomfort well correlated with the magnitude of acidification. Proton-sensing ion channels, transient receptor potential/vanilloid receptor subtype 1, and acid-sensing ion channel 3 are involved in acidosis-linked pain. However, whether recently identified proton sensing G-protein-coupled receptors (GPCRs) also have some contributions is unclear. Proton-sensing GPCRs, including OGR1, GPR4, G2A, and TDAG8, are fully activated at pH 6.4-6.8 in vitro. To understand whether the proton-sensing GPCRs are expressed in nociceptors, we cloned the four mouse genes and examined their tissue distribution and localization in pain-relevant loci, the dorsal root ganglion (DRG). The OGR1 family members were widely expressed in neuronal and non neuronal tissues. Their transcripts were expressed in the DRG, and most (75-82%) were present in small-diameter neurons responsible for nociception. Approximately 31-40% of total DRG neurons expressed at least two proton-sensing GPCRs. We have also demonstrated that gene expression of proton-sensing GPCRs is changed in ASIC3 knockout mice. Our finding suggests that proton-sensing GPCRs could have some roles in nociception or in compensation of loss of ASIC3 gene. PMID- 17720534 TI - Reelin and mDab1 regulate the development of hippocampal connections. AB - We analyze in this study the participation of Reelin and mDab1 in the development of hippocampal connections. We show that mDab1 is present in growth cones and axonal tracts of developing hippocampal afferents. mdab1-deficiency produces severe alterations in the entorhino-hippocampal and commissural connections identical to those described in reeler mice, including innervation of ectopic areas, formation of abnormal patches of fiber termination and a delay in the refinement of projections. Organotypic slice cultures combining tissue from mdab1 mutant and control mice demonstrate that the abnormalities observed in the mutant entorhino-hippocampal projection are caused by mdab1-deficiency in both the projecting neurons and target hippocampal cells. Axonal afferents that innervate the hippocampus react to Reelin by reducing axonal growth, and increasing growth cone collapse and axonal branching. Altogether these results indicate that Reelin and mDab1 participate in the development and refinement of hippocampal connections by regulating axonal extension, targeting and branching. PMID- 17720535 TI - Improved expression of kinases in Baculovirus-infected insect cells upon addition of specific kinase inhibitors to the culture helpful for structural studies. AB - As exemplified by three cases, we show that the addition of a small molecular weight inhibitor to the culture of Baculovirus-infected insect cells can dramatically improve the expression of a recombinant kinase. The expression of the tyrosine kinase KDR was sevenfold higher and mainly in a soluble form, when the KDR inhibitor PTK/ZK was added to the culture at the time of Baculovirus infection. The expression of the catalytic domain of the serine/threonine kinase PKCtheta, which is otherwise not possible with the Baculovirus expression system, was expressed mainly soluble at 120mg/L by the addition of the PKC inhibitor BIM XI to the culture of Baculovirus-infected insect cells. For Abl kinase, the expression could also be significantly increased by the addition of the Abl kinase inhibitor STI571 to the culture. For all three kinases, this method had previously been applied by us for the improved production of kinase/inhibitor complex protein, leading to the co-crystal structures. It is shown here at the cases KDR-PTK/ZK and PKCtheta-BIM XI, that the stimulatory effect of an inhibitor on kinase expression is applicable under many culture conditions. The presented method represents a valuable tool to obtain structural knowledge on kinase inhibitor complexes. PMID- 17720536 TI - Classification of cryo-electron sub-tomograms using constrained correlation. AB - Cryo-electron tomography (CET) is currently the only three-dimensional imaging technique capable of visualizing macromolecules in their cellular context at close-to-native conditions with a resolution in the nanometer range. An important component for the analysis of the data is their classification, which should discriminate among various macromolecules, conformational changes and interaction partners. Missing structure factors, typically in a wedge-shaped region in Fourier space if single-axis tilting is performed, hamper classification of cryo electron tomographic data. Here, we describe a classification method for three dimensional (3D) sub-tomograms extracted from cryo-electron tomograms, which takes the missing wedge into account and provides reliable results. The similarity of the individually aligned sub-tomograms is scored by constrained correlation. Subsequently, they are clustered based on their pairwise correlation values. In order to demonstrate the feasibility of this approach, we apply the proposed method to simulated tomographic data of the chaperone thermosome in different conformations. By comparison of the principal components of the resulting matrix we show that the proposed metric is significantly less prone to the orientation of the missing wedge compared to the unconstrained correlation. Moreover, we apply our classification method to an experimental dataset of GroEL with and without GroES, where we achieve a distinct discrimination between the putative GroEL and GroEL/GroES complexes. PMID- 17720537 TI - Jaw elevator silent periods in complete denture wearers and dentate individuals. AB - Functional meaning and underlying mechanisms of jaw elevator silent period (SP) have still not been completely understood. Since complete denture wearers (CDWs) have no periodontal receptors in their jaws, the aim was to examine SPs in CDWs and to compare it with dentate individuals (DIs). Thirty six DIs (skeletal/occlusal Class I) and 24 eugnath CDWs participated. EMG signals were registered using the EMGA-1 apparatus from the left and the right side anterior temporalis (ATM) and masseter muscles (MM). Ten registrations of an open-close clench (OCC) cycle were obtained for each individual. DIs had the average latency between 12.5 and 12.9 ms and always one single short inhibitory pause (IP) with complete inhibition of motoneurons (20.1-21.1 ms). On the other hand, in CDWs various types of SPs emerged: single or single prolonged SPs, double SPs, SPs with three IPs, periods of depressed muscle activity following the first, or the second IP, SPs with relative inhibition of motoneurons or even in several registrations the SP was missing. Unless more than one IP emerged, complete duration of inhibitory pauses (CDIP) was measured. CDIP varied from 37.17 to 42.49 ms. Average latencies were from 16.22 to 16.76 ms. Based on the results of this study it is obvious that both, the duration and the latencies were significantly longer in CDWs than in DIs (p<0.05), which can be explained by different mechanisms responsible for the muscle reflex behaviour. PMID- 17720538 TI - Effect of prolonged walking with backpack loads on trunk muscle activity and fatigue in children. AB - This study investigated the effect of prolonged walking with load carriage on muscle activity and fatigue in children. Fifteen Chinese male children (age=6 years, height=120.0+/-5.4 cm, mass=22.9+/-2.6 kg) performed 20-min walking trials on treadmill (speed=1.1 ms(-1)) with different backpack loads (0%, 10%, 15% and 20% body weight). Electromyography (EMG) signals from upper trapezius (UT), lower trapezius (LT) and rectus abdominis (RA) were recorded at several time intervals (0, 5, 10, 15 and 20 min), and were normalized to the signals collected during maximum voluntary contraction. Integrated EMG signal (IEMG) was calculated to evaluate the muscle activity. Power spectral frequency analysis was applied to evaluate muscle fatigue by the shift of median power frequency (MPF). Results showed that a 15% body weight (BW) load significantly increased muscle activity at lower trapezius when the walking time reached 15 min. When a 20% BW load was being carried, increase in muscle activity was found from 5 min, and muscle fatigue was found from 15 min. In upper trapezius, increase of muscle activity was not found within the 20-min period, however, muscle fatigue was found from 10 min. No increased muscle activity or muscle fatigue was found in rectus abdominis. It is suggested that backpack loads for children should be restricted to no more than 15% body weight for walks of up to 20 min duration to avoid muscle fatigue. PMID- 17720539 TI - Estimations of relative effort during sit-to-stand increase when accounting for variations in maximum voluntary torque with joint angle and angular velocity. AB - The main purpose of this study was to compare three methods of determining relative effort during sit-to-stand (STS). Fourteen young (mean 19.6+/-SD 1.2 years old) and 17 older (61.7+/-5.5 years old) adults completed six STS trials at three speeds: slow, normal, and fast. Sagittal plane joint torques at the hip, knee, and ankle were calculated through inverse dynamics. Isometric and isokinetic maximum voluntary contractions (MVC) for the hip, knee, and ankle were collected and used for model parameters to predict the participant-specific maximum voluntary joint torque. Three different measures of relative effort were determined by normalizing STS joint torques to three different estimates of maximum voluntary torque. Relative effort at the hip, knee, and ankle were higher when accounting for variations in maximum voluntary torque with joint angle and angular velocity (hip=26.3+/-13.5%, knee=78.4+/-32.2%, ankle=27.9+/-14.1%) compared to methods which do not account for these variations (hip=23.5+/-11.7%, knee=51.7+/-15.0%, ankle=20.7+/-10.4%). At higher velocities, the difference in calculating relative effort with respect to isometric MVC or incorporating joint angle and angular velocity became more evident. Estimates of relative effort that account for the variations in maximum voluntary torque with joint angle and angular velocity may provide higher levels of accuracy compared to methods based on measurements of maximal isometric torques. PMID- 17720540 TI - Cortical evolution and human behaviour. AB - All mammals have complex behaviours but these are generally stereotyped in nature and lack the flexibility of human behaviour. Can the flexibility of human behaviour be understood as an evolutionary extension of previous behaviours or is it a departure? Theories pertaining to this question have a long history including, now refuted, theories on neoteny. This paper, using an evolutionary developmental biology approach, outlines some existing theories and suggests some novel ideas. Previous trends during brain evolution are determined by outlining the phylogeny and ontogeny of the six layered mammalian isocortex with particular reference to the primate lineage. These evolutionary trends are extrapolated to hominids to postulate the effect of increasingly large brains. The palaeoanthropological literature is cited to debate the nature and time course of behavioural change during hominid evolution. In particular, when was truly flexible behaviour first evident, and did it occur gradually or suddenly? The proposed isocortical and behavioural changes during hominid evolution are then equated to determine if modern human behaviour can be seen as part of a continuum. It is concluded that a continuation of previous trends in isocortical evolution maybe inadequate to explain human behavioural flexibility. Several possible departures from previous trends that would be compatible with increased behavioural flexibility are suggested. These mainly relate to evolutionary changes in the later stages of isocortical development and in particular during the activity-dependant phase when cortico-cortical connections are refined. PMID- 17720541 TI - Behavior on the water maze platform: relationship to learning and open field exploration in aged and adult rats. AB - In the present study we examined whether age-related deficits in the water maze could be accounted for by changes in the behavior on the platform, and whether platform behavior represents some form of exploration, akin to that seen in the open field. Twenty-seven aged and 8 adult rats (26 and 3 months old Wistar rats, respectively) were tested in an empty open field and spatial object exploration task, followed by 9 days of escape learning in a water maze. The aged as compared to the adults exhibited lower levels of open field activity and were deficient in the object displacement task. Escape deficits in the water maze and reduced activity levels on the platform were also found. In the aged, water maze performance was correlated with behavior on the platform, including quiescence, orienting-like activity and turning behavior, a form of axial rotation. In both age groups, turning behavior was also correlated with exploratory activity in the open field. In conclusion, the results support the hypothesis that age-related impairments in the water maze relate to changes in platform behavior, which, in turn, might reflect exploratory activity. PMID- 17720542 TI - Physical exercise program reverts the effects of pinealectomy on the amygdala kindling development. AB - Several studies have demonstrated the anticonvulsant effect of melatonin. In view of the positive effects of physical exercise in epilepsy, this study analyzed the influence of physical exercise program on the amygdala kindling development in pinealectomized rats. Animals were divided into six groups: pinealectomized rats (PX), sham rats (SHAM), control rats (CTL), pinealectomized rats submitted to an aerobic exercise program (PX ATL), sham rats submitted to an aerobic exercise program (SHAM ATL) and control rats submitted to an aerobic exercise program (CTL ATL). The stimulus parameters consisted of 60 Hz frequency, diphasic square pulses of 1 ms duration applied for 2 s. The mean number of stimulations and the after-discharge (AD) duration for each stage of kindling were similar among CTL and SHAM animals. PX animals showed particular characteristics during kindling development. They did not present stage 1 and spent a shorter time in stage 2 in relation to the CTL and SHAM animals. Consequently, the AD duration and number of stimulations required to reach stage 5 was lower for the PX group when compared to the CTL and SHAM groups. Concerning the exercising groups, CTL ATL and SHAM ATL animals spent a higher time in stage 1 compared to CTL and SHAM groups. Thus, CTL ATL animals also presented a higher number of stimulations in stage 5 compared to CTL animals. The stage 1 not observed in PX animals was present in PX ATL. Consequently, the number of stimulations required to reach stage 5 was statistically higher for the PX ATL group in relation to the PX group. Our results demonstrate that the acceleration in the kindling development of pinealectomized animals can be reverted by physical exercise. PMID- 17720544 TI - Role of dopamine D1 receptors in novelty seeking in adult female Long-Evans rats. AB - Adult Long-Evans ovariectomized female rats received injections of the DA D1 antagonist SCH 23390 (0, 0.03 and 0.3mg/kg, i.p.) and were observed in an open field apparatus (OFA) with a novel object. Results indicate that a significant effect of SCH 23390 was found on several measures of novelty seeking and activity, with the high dose producing a significant decrease in (1) approaches to and (2) rears while approaching the novel object, (3) latency to interact with the novel object, (4) in time interacting with the novel object, (5) anxious behavior (as measured by rears) and (6) locomotor activity (LMA), as compared to both the saline and low dose. Interestingly, the effects of SCH 23390 on approaches and rears were not significant when LMA was factored into the analysis (repeated measures ANCOVA), however, marked results were still found on time interacting with the novel object. These data demonstrate that SCH 23390 produced dose-dependent effects on novelty seeking that were independent of LMA, implicating D1 receptors in the incentive-motivational aspect of novelty seeking in adult gonadectomized female rats. PMID- 17720543 TI - The sea urchin embryo, an invertebrate model for mammalian developmental neurotoxicity, reveals multiple neurotransmitter mechanisms for effects of chlorpyrifos: therapeutic interventions and a comparison with the monoamine depleter, reserpine. AB - Lower organisms show promise for the screening of neurotoxicants that might target mammalian brain development. Sea urchins use neurotransmitters as embryonic growth regulatory signals, so that adverse effects on neural substrates for mammalian brain development can be studied in this simple organism. We compared the effects of the organophosphate insecticide, chlorpyrifos in sea urchin embryos with those of the monoamine depleter, reserpine, so as to investigate multiple neurotransmitter mechanisms involved in developmental toxicity and to evaluate different therapeutic interventions corresponding to each neurotransmitter system. Whereas reserpine interfered with all stages of embryonic development, the effects of chlorpyrifos did not emerge until the mid blastula stage. After that point, the effects of the two agents were similar. Treatment with membrane permeable analogs of the monoamine neurotransmitters, serotonin and dopamine, prevented the adverse effects of either chlorpyrifos or reserpine, despite the fact that chlorpyrifos works simultaneously through actions on acetylcholine, monoamines and other neurotransmitter pathways. This suggests that different neurotransmitters, converging on the same downstream signaling events, could work together or in parallel to offset the developmental disruption caused by exposure to disparate agents. We tested this hypothesis by evaluating membrane permeable analogs of acetylcholine and cannabinoids, both of which proved effective against chlorpyrifos- or reserpine-induced teratogenesis. Invertebrate test systems can provide both a screening procedure for mammalian neuroteratogenesis and may uncover novel mechanisms underlying developmental vulnerability as well as possible therapeutic approaches to prevent teratogenesis. PMID- 17720545 TI - Oxytocin neurons in the supraoptic nucleus receive excitatory inputs from the bilateral dorsomedial hypothalamic nuclei. AB - To examine whether inputs from the dorsomedial hypothalamic nucleus (DMH) alter the discharge of putative oxytocin (OT) neurons with hypothesis that excitation of DMH neurons would increase the activity of OT neurons, electrical stimulation was applied to the DMH in both sides of the hypothalamus while electrical activity of single OT neurons in the supraoptic nucleus (SON) was recorded in urethane-anesthetized lactating rats. About half of the OT neurons showed orthodromic excitation or inhibition followed by excitation in response to electrical stimulation of the DMH on both sides. Continuous electrical stimulation of the DMH both ipsi- and contralateral to the recording side at 10 50 Hz for 30-60 s increased firing rate in 58% of OT neurons tested. Continuous electrical stimulation of the DMH not only excited spiking activity of single OT neurons but also increased intramammary pressure. The results may suggest that some of the projections from the DMH to the SON are bilateral and possibly contribute to coordinated bilateral activation of OT neurons in the hypothalamus during the milk-ejection reflex. PMID- 17720546 TI - Motor and somatosensory evoked potentials in Autosomal Dominant Hereditary Spastic Paraparesis (ADHSP) linked to chromosome 2p, SPG4. AB - The aim of our study was to evaluate Motor Evoked Potentials (MEPs) and cortical excitability, using Transcranial Magnetic Stimulation (TMS) as well as short latency Somatosensory Evoked Potentials (SEPs) in Autosomal Dominant Hereditary Spastic Paraparesis (ADHSP) patients. MEPs were recorded from upper and lower limb muscles in 12 patients (7 m and 5f) affected by ADHSP with spastin mutation (SPG4). We measured: (i) motor threshold (MTh); (ii) total motor conduction time (TMCT); (iii) direct and indirect central motor conduction time (d-CMCT and i CMCT) calculated by subtracting from the cortical latency those obtained on magnetic spinal stimulation (d-PMCT) and via the F-wave method (i-PMCT); (iv) MEP amplitude (MEP/Mmax ratio%) and (v) duration of the cortical silent period (CSP). Latency, amplitude and persistence of the F-wave obtained with electrical nerve stimulation were also considered; H reflex was also tested from lower extremities. SEPs were recorded from spine and scalp sites following median and posterior tibial nerve stimulation; conventional latency and amplitude measurements were performed. In a comparison with the control group, the MTh recording from lower limbs was significantly higher (67.5 +/- 7.7% versus 52.5 +/ 6.9%), MEPs were absent in one case and showed reduced amplitude in the remainders (22.9 +/- 12.6% versus 66.3 +/- 25.9% of M wave); TMCT resulted to be abnormal (36.5 +/- 3.9 ms versus 27.1 +/- 1.4 ms) and d-CMCT as well as i-CMCT were significantly prolonged (23.1 +/- 3.5 ms versus 13.8 +/- 1.3 ms; and 20.1 +/ 3.4 ms versus 10.6 +/- 1.3 ms, respectively). The CSP, which was normal from the hands, was significantly shortened from the legs and correlated with spasticity scoring (Ashworth scale). Cortical SEPs from lower limbs were abnormal in all cases, whereas SEPs by stimulation of median nerves were normal; F-wave parameters from upper limbs showed no abnormalities, whereas an increased persistence was detected from lower limbs; H reflex amplitudes resulted larger compared with controls. Moreover, shortening of the CSP, being correlated with the Ashworth scale, can be considered an electrophysiological marker of spasticity that seems to arise from impairment of the supraspinal or intracortical inhibitory pathways with an additional contribution of increased segmental motor neuron excitability. These data prove the existence of comparable neurophysiological abnormalities in ADHSP with spastin mutation (SPG4) when long ascending and descending pathways are involved. PMID- 17720547 TI - Activity in medial prefrontal cortex during cognitive evaluation of threatening stimuli as a function of personality style. AB - Cognitive evaluation of emotional stimuli involves a network of brain regions including the medial prefrontal cortex (mPFC). However, threatening stimuli may be perceived with differential salience in different individuals. The goal of our study was to evaluate how different personality styles are associated with differential modulation of brain activity during explicit recognition of fearful and angry facial expressions. Twenty-eight healthy subjects underwent fMRI. Based on a cognitivist model, subjects were categorized according to how they attribute salience to emotional stimuli and how they regulate their emotional activation. We compared 14 phobic prone (PP) subjects, whose identity is more centered on the inner experience ("inward") and around control of environmental threat, and 14 eating disorders prone (EDP) subjects, whose identity is more centered on external referential contexts ("outward") and much less around control of threatening stimuli. During fMRI subjects either matched the identity of one of two angry and fearful faces to that of a simultaneously presented target face or identified the expression of a target face by choosing one of two simultaneously presented linguistic labels. The fMRI results indicated that PP subjects had greater mPFC activation when compared with EDP subjects during cognitive labeling of threatening stimuli. Activity in the mPFC also correlated with personality style scores. These results demonstrate that PP subjects recruit greater neuronal resources in mPFC whose activity is associated with cognitive aspects that are closely intertwined with emotional processing. These findings are consistent with the contention that cognitive evaluation and salience of emotional stimuli are associated with different personality styles. PMID- 17720548 TI - The control of equilibrium in Parkinson's disease patients: delayed adaptation of balancing strategy to shifts in sensory set during a dynamic task. AB - Processing of sensory information, timing operations and set-shifting can be affected in Parkinson's disease (PD) patients. We investigated their capacity and swiftness to pass from a kinaesthetic- to a vision-dependent behaviour during dynamic balancing on a continuously moving support base. Nineteen on-phase PD patients and 13 age-matched normal subjects stood on a platform continuously translating in the antero-posterior direction at 0.2 Hz. Body segment oscillations were identified by a stereophotogrammetric device and electromyogram (EMG) was recorded from tibialis anterior and soleus. Under constant visual conditions, both patients and normal subjects roughly stabilised head and trunk in space with eyes open (EO) but followed the platform displacement with eyes closed (EC). Amplitude and variability of the periodic EMG bursts were smaller with EO than EC. Constant visual-condition trials were intermingled with trials in which subjects opened (EC-EO) or closed (EO-EC) the eyes in response to an acoustic signal. Both patients and normal subjects changed kinematics and EMG patterns to those appropriate for the new visual condition. However, PD patients were slower in changing their behaviour under the EC-EO condition. These findings show abnormal temporal features in balancing strategy adaptation when shifting from kinaesthetic to visual reference in PD. The delay in the implementation of the vision-dependent behaviour was unexpected, given the advantage vision is supposed to confer to motor performance in PD. This condition may play a major role in the instability of patients performing dynamic postural tasks under changing sensory conditions. PMID- 17720549 TI - Intranasally delivered TGF-beta1 enters brain and regulates gene expressions of its receptors in rats. AB - This study is aimed to evaluate the brain distribution of transforming growth factor-beta1 (TGF-beta1) following intranasal administration and the subsequent biological effects of TGF-beta1. Adult rats were given recombinant human TGF beta1 (rhTGF-beta1) or vehicle solution intranasally. TGF-beta1 concentrations were significantly raised in several brain regions and the trigeminal nerve following intranasal delivery. The elevation appeared within 30 min and was sustained for at least 6 h, reaching its greatest level at 60 min. A concentration gradient in the central nervous system (CNS) regions was produced during the first 2 h after intranasal administration, with the OB presenting a significantly higher concentration than any other CNS regions. The nasally administered TGF-beta1 subsequently regulated gene expressions of its two receptors (TGF-beta receptor types I and II) in vivo, but did not affect mRNA level of TGF-beta1 itself. Our results suggest that TGF-beta1 can be transported into the CNS via the olfactory and trigeminal pathways, and may consequently exert its biological effects by regulating gene expressions of its receptors. Intranasal administration of neurotrophic factors may offer a potential strategy for treating some CNS disorders. PMID- 17720550 TI - Imunoreactivity of zinc transporter 7 (ZNT7) in mouse dorsal root ganglia. AB - In the present study, we showed for the first time the localization of ZNT7 immunoreactivity in the mouse dorsal root ganglion (DRG) by means of immunohistochemistry and confocal laser scanning microscopy. Our results revealed that ZNT7 immunoreactivity was abundantly expressed in the nerve cells of the mouse DRG. Strong ZNT7 immunoreactivity was predominantly distributed in the perinuclear region of positive cells, while the nuclei were devoid of staining. Double immunofluorescence labeling of ZNT7 and TGN38 revealed a colocalization of the two antigens in the Golgi apparatus. In addition, the presence of labile zinc ions was detected with in vivo zinc selenium autometallography (AMG). AMG observations showed that the zinc staining pattern was also predominately located in the perinuclear Golgi area, like the ZNT7 immunostaining pattern in the DRG. These observations strongly suggest that ZNT7 may play an important role in facilitating zinc transport into the Golgi apparatus from the cytosol in the mouse DRG. PMID- 17720551 TI - The role of excitatory amino acids and substance P in the mediation of the cough reflex within the nucleus tractus solitarii of the rabbit. AB - We hypothesized that cough evoked by mechanical stimulation of the tracheobronchial tree in the rabbit is primarily mediated by glutamatergic neurotransmission at the level of the caudal portions of the medial subnucleus of the nucleus tractus solitarii (NTS) and the lateral commissural NTS where cough related afferents terminate, and that this reflex is potentiated by local release of substance P. To test our hypothesis, we performed bilateral microinjections (30-50 nl) of ionotropic glutamate receptor antagonists or substance P into these locations in pentobarbitone anaesthetized, spontaneously breathing rabbits. Blockade of NMDA and non-NMDA receptors by 50mM kynurenic acid abolished the cough reflex without affecting the Breuer-Hering inflation reflex or the pulmonary chemoreflex. Blockade of non-NMDA receptors using 10mM CNQX or 5mM NBQX caused identical effects. Blockade of NMDA receptors by 10mM D-AP5 strongly reduced, but did not abolish cough responses. Microinjections of 1mM substance P increased peak and rate of rise of abdominal muscle activity as well as cough number. These results are the first to provide evidence that ionotropic glutamate receptors, especially non-NMDA receptors, located within specific regions of NTS are primarily involved in the mediation of cough evoked by mechanical stimulation of the tracheobronchial tree in the rabbit. Present findings on substance P cough enhancing effects extend previous observations and are relevant to the tachykinin mediated central sensitization of the cough reflex. They also may provide hints for further studies on centrally acting antitussive drugs. PMID- 17720552 TI - What is where and why it is important. PMID- 17720553 TI - Audit of healthcare provision for UK prisoners with suspected epilepsy. AB - PURPOSE: To describe the prevalence and nature of epileptic seizure disorders in a typical UK prison and compare the care offered to prisoners to the recommendations of the National Institute for Clinical Excellence (NICE). METHODS: Over a 14-month period, all prisoners identified as having epilepsy were registered by prison primary healthcare services at a category 'C' prison holding 640 male adults. Prison and National Health Service health records were reviewed, prisoners were re-assessed by members of a specialist secondary care service based in the local general hospital NHS. RESULTS: Twenty-six prisoners were thought to have epilepsy. 61.5% of diagnoses had not been made by epilepsy specialists, 73.1% had uncontrolled seizures, only 19.2% had had computed tomography, none magnetic resonance imaging. At review, 30.8% of prisoners were thought to require neuroimaging, 19.2% cardiac investigations. The diagnosis of epilepsy was confirmed in only 57.9% of those prisoners considered to have the condition by prison healthcare services. 53.8% of those prisoners confirmed as having epilepsy had not had a medical review in the past 12 months; 63.2% required a change in their antiepileptic drugs (AEDs). CONCLUSION: Although the prevalence of epilepsy in this prison population appeared high at first sight, a critical review of the diagnoses reduced the difference to the prevalence of epilepsy in the population at large. Fewer prisoners than expected achieved seizure control. Collaboration with specialist epilepsy services was poor. There were significant discrepancies between the healthcare provision in prison and the NICE epilepsy guidelines. PMID- 17720554 TI - Effect of neurotrophins on differentiation, calcification and proliferation in cultures of human pulp cells. AB - Neurotrophins (NTs) are expressed during tooth development. However, little is known about a role of NTs in differentiation of pulp cells into mineralizing cells. In this study, mRNA expressions of hard tissue-related proteins, calcification and proliferation are examined in cultures of human pulp (HP) cells. Nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin (NT)-3 and NT-4/5 increased the mRNA levels of dentin sialophsphoprotein, alkaline phosphatase, osteopontin, type I collagen and bone morphogenetic protein-2 and mineral deposition in cultures of HP cells. The increased levels and manners varied, depending on the concentrations of NTs and hard-tissue related protein tested. On the other hand, only NGF significantly stimulated DNA synthesis in cultures of HP cells. These findings suggest that NTs characteristically regulate hard-tissue related protein expression, calcification and proliferation in pulp cells. NTs may accelerate pulp cell differentiation. PMID- 17720555 TI - Morphological changes in dendritic spines of Purkinje cells associated with motor learning. AB - Experience-dependent changes of spine structure and number may contribute to long term memory storage. Although several studies demonstrated structural spine plasticity following associative learning, there is limited evidence associating motor learning with alteration of spine morphology. Here, we investigated this issue in the cerebellar Purkinje cells using high voltage electron microscopy (HVEM). Adult rats were trained in an obstacle course, demanding significant motor coordination to complete. Control animals either traversed an obstacle-free runway or remained sedentary. Quantitative analysis of spine morphology showed that the density and length of dendritic spines along the distal dendrites of Purkinje cells were significantly increased in the rats that learned complex motor skills compared to active or inactive controls. Classification of spines into shape categories indicated that the increased spine density and length after motor learning was mainly attributable to an increase in thin spines. These findings suggest that motor learning induces structural spine plasticity in the cerebellar Purkinje neurons, which may play a crucial role in acquiring complex motor skills. PMID- 17720556 TI - Pyrantel in small animal medicine: 30 years on. AB - Pyrantel, a tetrahydropyrimidine nicotinic agonist anthelmintic, has been used in companion animal medicine since the 1970s to control two important nematode groups, the hookworms and the roundworms. Given the zoonotic potential of these parasites, pyrantel has served a dual role in helping to protect the health of both companion animals and the public for more than 30 years. This review describes the history and mechanism of action of this drug, and collates evidence that resistance to pyrantel has developed in at least one canine nematode, the hookworm Ancylostoma caninum. The role of in vitro diagnosis tests in managing anthelmintic resistance in companion animal parasites is discussed, as are management practices that may reduce the rate at which resistance develops. PMID- 17720557 TI - Use of clinical MR scanners for small rodent imaging. PMID- 17720558 TI - Cranial MRI of small rodents using a clinical MR scanner. AB - Increasing numbers of small animal models are in use in the field of neuroscience research. Magnetic resonance imaging (MRI) provides an excellent method for non invasive imaging of the brain. Using three-dimensional (3D) MR sequences allows lesion volumetry, e.g. for the quantification of tumor size. Specialized small bore animal MRI scanners are available for high-resolution MRI of small rodents' brain, but major drawbacks of this dedicated equipment are its high costs and thus its limited availability. Therefore, more and more research groups use clinical MR scanners for imaging small animal models. But to achieve a reasonable spatial resolution at an acceptable signal-to-noise ratio with these scanners, some requirements concerning sequence parameters have to be matched. Thus, the aim of this paper was to present in detail a method how to perform MRI of small rodents brain using a standard clinical 1.5 T scanner and clinically available radio frequency coils to keep material costs low and to circumvent the development of custom-made coils. PMID- 17720560 TI - Experimental nerve imaging at 1.5-T. AB - Experimental lesions of the peripheral nerve system can be visualized in vivo by magnetic resonance imaging (MRI). Many studies of the rat peripheral nervous systems were performed on dedicated animal MR scanners with a high magnetic field strength for good spatial resolution. Here, we present an MR protocol to study experimental lesions of the rat nervous system with clinical 1.5-T MR scanners and commercially available coils. Using a three-sequence approach (T1-weighted imaging, fat-saturated T2-weighted imaging and fat-saturated T1-weighted imaging with Gd-DTPA in the same plane), the relevant signal changes of the lesioned nerve can be visualized and separated from other structures, e.g., blood vessels. Furthermore, we give an overview on different types of contrast agents used for peripheral nerve MR imaging and MR findings in selected experimental models of rat peripheral nerve injury. PMID- 17720559 TI - Diffusion weighted imaging in small rodents using clinical MRI scanners. AB - Diffusion weighted imaging (DWI) has emerged as a unique and powerful non invasive magnetic resonance imaging (MRI) technique with a major potential impact on imaging-based diagnosis in a variety of clinical applications including oncology and tissue viability assessment. In light of increasing demand for applying this technique in preclinical investigations using small animals, we have explored the potentials of a clinical magnet for acquiring the DWI in rats and mice with either cerebral ischemia or solid tumors. Through technical adaptation and optimization, we have been able to perform a series of clinically relevant animal studies with conclusions based on DWI quantification. Focusing more on practical aspects and cross-referencing with the current literature, this paper is aimed to summarize our ongoing DWI studies on small rodents with stroke and tumors, and to provide protocols for researchers to replicate similar techniques in their own preclinical and clinical studies. PMID- 17720561 TI - Computer-assisted measurement of vessel shape from 3T magnetic resonance angiography of mouse brain. AB - Blood vessel morphology (vessel radius, branching pattern, and tortuosity) is altered by a multitude of diseases. Although murine models of human pathology are important to the investigation of many diseases, there are few publications that address quantitative measurements of murine vascular morphology. This report outlines methods of imaging mice in vivo using magnetic resonance angiograms obtained on a clinical 3T unit, of defining mouse vasculature from these images, and of quantifying measures of vessel shape. We provide examples of both healthy and diseased vasculature and illustrate how the approach can be used to assess pathology both visually and quantitatively. The method is amenable to the assessment of many diseases in both human beings and mice. PMID- 17720563 TI - Abdominal magnetic resonance imaging in small rodents using a clinical 1.5 T MR scanner. AB - Because of superior soft-tissue contrast compared to other imaging techniques, non-invasive abdominal magnetic resonance imaging (MRI) is ideal for monitoring organ regeneration, tissue repair, cancer stage, and treatment effects in a wide variety of experimental animal models. Currently, sophisticated MR protocols, including technically demanding procedures for motion artefact compensation, achieve an MRI resolution limit of < 100 microm under ideal conditions. However, such a high spatial resolution is not required for most experimental rodent studies. This article describes both a detailed imaging protocol for MR data acquisition in a ubiquitously and commercially available 1.5 T MR unit and 3 dimensional volumetry of organs, tissue components, or tumors. Future developments in MR technology will allow in vivo investigation of physiological and pathological processes at the cellular and even the molecular levels. Experimental MRI is crucial for non-invasive monitoring of a broad range of biological processes and will further our general understanding of physiology and disease. PMID- 17720562 TI - Cardiac magnetic resonance imaging in small rodents using clinical 1.5 T and 3.0 T scanners. AB - Cardiac magnetic resonance (CMR) imaging can provide noninvasive, high resolution images of heart anatomy, viability, perfusion, and function. However, the adoption of clinical CMR imaging protocols for small rodents has been limited due to the small heart size and rapid heart rates. Therefore, most CMR studies in small rodents have been performed on non-clinical, high-field MR magnets. Because such high-field systems are not readily available at most institutions, the technical aspects that are needed to perform CMR on clinical 1.5 T and 3.0 T MR scanners are presented in this paper. Equipment requirements are presented, and a comprehensive description of the methods needed to complete a CMR exam including the animal preparation, imaging, and image analysis are discussed. In addition, the advanced applications of myocardial tagging and delayed-contrast-enhanced imaging are reviewed for the assessment of regional contractile function and myocardial viability, respectively. PMID- 17720564 TI - Technical aspects: development, manufacture and installation of a cryo-cooled HTS coil system for high-resolution in-vivo imaging of the mouse at 1.5 T. AB - Signal-to-noise ratio improvement is of major importance to achieve microscopic spatial resolution in magnetic resonance experiments. Magnetic resonance imaging of small animals is particularly concerned since it typically requires voxels of less than (100 microm)(3) to observe the small anatomical structures having size reduction by a factor of more than 10 as compared to human being. The signal-to noise ratio can be increased by working at high static magnetic field strengths, but the biomedical interest of such high-field systems may be limited due to field-dependent contrast mechanisms and severe technological difficulties. An alternative approach that allows working in clinical imaging system is to improve the sensitivity of the radio-frequency receiver coil. This can be done using small cryogenically operated coils made either of copper or high-temperature superconducting material. We report the technological development of cryo-cooled superconducting coils for high-resolution imaging in a whole-body magnetic resonance scanner operating at 1.5 T. The technological background supporting this development is first addressed, including HTS coil design, simulation tools, cryogenic mean description and electrical characterization procedure. To illustrate the performances of superconducting coils for magnetic resonance imaging at intermediate field strength, in-vivo mouse images of various anatomic sites acquired with a 12 mm diameter cryo-cooled superconducting coil are presented. PMID- 17720565 TI - Anaesthesia of small rodents during magnetic resonance imaging. AB - The use of experimental animals for magnetic resonance studies requires anaesthesia to provide immobility and acquire signals with minimal stress and maximal reproducibility. However, the conduct of anaesthesia within a magnetic resonance imaging (MRI) suite implicates many problems, because most of the anaesthetic and monitoring equipment contains ferromagnetic substances. To decrease disturbances during anaesthesia and make data interpretation more accurate, it is mandatory that investigators become familiar with methods and physiologic effects of anaesthesia under these special conditions. This article is intended to give an overview of anaesthetic medication, administration routes and practical instructions for anaesthesia in small rodents during MRI. PMID- 17720566 TI - Current issues and perspectives in small rodent magnetic resonance imaging using clinical MRI scanners. AB - Small rodents such as mice and rats are frequently used in animal experiments for several reasons. In the past, animal experiments were frequently associated with invasive methods and groups of animals had to be killed to perform longitudinal studies. Today's modern imaging techniques such as magnetic resonance imaging (MRI) allow non-invasive longitudinal monitoring of multiple parameters. Although only a few institutions have access to dedicated small animal MR scanners, most institutions carrying out animal experiments have access to clinical MR scanners. Technological advances and the increasing field strength of clinical scanners make MRI a broadly available and viable technique in preclinical in vivo research. This review provides an overview of current concepts, limitations, and recent studies dealing with small animal imaging using clinical MR scanners. PMID- 17720567 TI - Ultrasound biomicroscopic characteristics of the anterior segment in primary congenital glaucoma. AB - PURPOSE: To evaluate qualitatively and quantitatively ultrasound biomicroscopic (UBM) features of the anterior segment in eyes with primary congenital glaucoma. METHODS: UBM of 45 eyes of patients with primary congenital glaucoma (39 previously operated and 6 unoperated eyes) and 28 control eyes were included in this study. UBM parameters were correlated with ocular biometry. Iris thickness, ciliary body thickness, ciliary body-lens distance, posterior chamber depth, and anterior chamber angle were measured and compared with control eyes. Other features of the anterior segment were qualitatively evaluated. RESULTS: A thin, stretched-out ciliary body and abnormal tissue at the iridocorneal angle were features seen in 90% of UBM scans. Iris thickness and stretched zonules correlated with the axial length (r = -0.6 and 0.58, respectively; p = 0.04) but not with the mean corneal diameter. Abnormal insertion of the ciliary body to the posterior surface of the iris was noted in eight eyes (17%). CONCLUSIONS: The present study documents characteristic anterior segment dysplasia and ciliary body anomalies in patients with primary congenital glaucoma. PMID- 17720568 TI - Surgical implications of the superior oblique frenulum. AB - BACKGROUND: The superior oblique frenulum is a fascial membrane that prevents substantial separation of the superior rectus muscle and SO tendon. METHODS: In three patients, the superior rectus muscle was disinserted and temporarily suspended 6, 8, 10, 12, and 14 mm in random order from its insertion. The change in position of the anterior edge of the superior oblique tendon from the superior rectus muscle insertion was measured before and after severing the frenulum structure. In four other patients undergoing superior oblique recession, the superior oblique tendon was disinserted at its insertion temporally. The amount of recession that spontaneously occurred was measured before and after severing the frenulum. RESULTS: In the first group, there was essentially a one-to-one correlation between the posterior movement of the superior oblique tendon and the amount of superior rectus recession for recessions up to 10 mm. After severing the frenulum, the anterior portion of the superior oblique tendon was positioned less posteriorly. It measured less than 1.2 mm for superior rectus recessions up to 14 mm. For the second group, the mean suspension distance of the cut end of the disinserted superior oblique tendon was 2.4 +/- 0.4 mm before stripping the frenulum as compared with 8.5 +/- 0.7 mm after stripping the frenulum (Student's t-test, p = 0.0011). CONCLUSIONS: The frenulum pulls the superior oblique tendon posteriorly as the superior rectus muscle is recessed and constrains the superior oblique tendon after disinsertion. How this connection is handled at the time of surgery may have implications for superior rectus recessions and superior oblique tendon surgery. PMID- 17720569 TI - Recurrent bleeding following traumatic hyphema due to mild hemophilia B (Christmas disease). AB - Traumatic hyphemas generally resolve spontaneously. When recurrent bleeding occurs, a coagulopathy should be suspected. We present a unique case of a traumatic hyphema with recurrent bleeding in association with mild hemophilia B (factor IX deficiency). PMID- 17720570 TI - Traumatic pediatric cataract: a decade of follow-up after Artisan aphakia intraocular lens implantation. AB - PURPOSE: To describe the long-term clinical outcome of Artisan((R)) aphakia intraocular lens (IOL; Ophtec, Groningen, The Netherlands) implantation in five aphakic eyes of five children, without capsular support, after cataract extraction following penetrating ocular trauma. METHODS: The charts of the five children were retrospectively reviewed. The data collected included follow-up time, nature of injury, age at cataract extraction and IOL implantation, visual outcome, endothelial cell counts, complications, and subsequent surgical interventions. RESULTS: Average follow-up was 11.0 years (range, 8.0-14.6 years). All eyes had a corneal perforation with various degrees of anterior segment injury. Mean patient age at lens extraction was 7.8 years (range, 5.6-10.2 years). Mean age at Artisan aphakia IOL implantation was 7.9 years (range, 5.7 10.2 years). The best spectacle-corrected visual acuity at last follow-up was 20/40 or better in four eyes. Mean endothelial cell loss compared with the healthy fellow eye was 40%. No patients experienced IOL dislocation, corneal decompensation, chronic anterior uveitis, cystoid macular edema, or iris atrophy. One eye had a retinal detachment 19 months after primary injury and needed vitreoretinal surgery. CONCLUSIONS: The Artisan aphakia IOL offers a useful alternative for correction of traumatic childhood aphakia. Although we only have results of a small number of patients, taking into account our long follow-up period, we feel that implantation of the Artisan aphakia IOL can be considered a treatment option in aphakic eyes of children that lack capsular support due to trauma. PMID- 17720571 TI - Treatment of capillary hemangiomas causing refractive and occlusional amblyopia. AB - PURPOSE: Capillary hemangiomas of the eyelid and orbit are treated when amblyopia secondary to anisometropic astigmatism or pupillary occlusion is present or when rapid growth of the hemangioma threatens to occlude the pupil. The goal of this study was to determine whether treatment of hemangiomas resolves or prevents occlusion or results in decrease in astigmatism. METHODS: The records of 54 patients who underwent treatment for reduction in the size of a capillary hemangioma causing amblyopia or threatened amblyopia in two pediatric ophthalmology practices were reviewed. RESULTS: Twenty-eight patients were treated for amblyopia due to anisometropic astigmatism. The average amount of pretreatment astigmatism was 2.71 D, while the average amount of post-treatment astigmatism was 0.46 D. Fifteen of these patients could be tested for optotype visual acuity and all had vision acuity of 20/40 or better. Only 1 of the 15 patients treated for threatened occlusion of the pupil developed occlusion. Six of these patients cooperated with optotype visual acuity and all had vision acuity of 20/30 or better. Eleven patients were treated for pupillary occlusion. Occlusion resolved in all cases. Of the five patients treated for occlusion who cooperated with optotype visual acuity, two had a vision acuity of 20/100 or worse. CONCLUSIONS: Treatment to reduce the size of capillary hemangiomas results in resolution of occlusion, reduction in astigmatism, and prevention of pupillary occlusion. Those with occlusion are at higher risk for severe residual amblyopia and require prompt and definitive treatment. PMID- 17720572 TI - Familial unilateral ectopia lentis. AB - Ectopia lentis is almost always a bilateral condition, although it may be asymmetric in some cases of Marfan syndrome. Unilateral ectopia lentis has been associated with trauma and with intraocular tumors. We report two siblings with isolated unilateral ectopia lentis who had no evidence of underlying abnormality or of trauma. PMID- 17720573 TI - Randot Preschool Stereoacuity Test: normative data and validity. AB - INTRODUCTION: The Randot Preschool Stereoacuity Test is a widely used three-book test for the assessment of binocular status. Using a prototype, we previously reported high testability in children as young as 3 years, validity data, and some normative data. Here we report extensive normative and validity data for the final version of the test. In addition, we report normative data for a new, fourth book that adds finer disparities. METHODS: The Randot Preschool Stereoacuity Test was administered to 4355 normal children aged 3 to 18 years and 39 adults in multiple settings. In addition, the Randot Preschool Stereoacuity Test along with the new, fourth book that added 30 arcsec and 20 arcsec disparity levels was administered to 1402 normal children aged 3 to 18 years and 33 normal adults. Both the four-book Randot((R)) Preschool Stereoacuity Test and the Randot circles were administered to 242 patients with amblyogenic conditions aged 3 to 18 years. RESULTS: Mean normal stereoacuity improved from 100 arcsec at 3 years of age to 60 arcsec by 5 years and 40 arcsec by 7 years. The lower limit of normal was 400 arcsec at 3 years, 200 arcsec at 4 years, and 60 arcsec at 7 years. Using the new four-book version, further improvement in mean stereoacuity could be appreciated beyond 7 years of age to 30 arcsec in the 11- to 18-year-old and adult groups. Among the 242 patients, Randot Preschool Stereoacuity Test stereoacuity was strongly associated with Randot circle stereoacuity (chi(2) = 261.0, p < 0.001). CONCLUSIONS: Normative data for the Randot Preschool Stereoacuity Test show a monotonic improvement of stereoacuity from age 3 years through the teen years. Patient data support the validity of the Randot Preschool Stereoacuity Test. PMID- 17720574 TI - Unilateral restrictive ophthalmoplegia and enophthalmos associated with an intraorbital tissue band. AB - Fibrosis of the extraocular muscles can be congenital or acquired. Acquired causes include trauma, myositis, thyroid eye disease, infection, and metastases. Congenital fibrosis of the extraocular muscles (CFEOM) runs in families and is known to have a genetic basis. It has been classified by Brown, Hansen, and Harley et al into the five following types: general fibrosis syndrome; fibrosis of the inferior rectus (IR) with blepharoptosis; strabismus fixus; vertical retraction syndrome; and unilateral fibrosis, blepharoptosis, and enophthalmos syndrome. In this report, a case of unilateral fibrosis with enophthalmos and blepharoptosis due to a fibrous band is described. PMID- 17720576 TI - Health assessment of Black-crowned Night-herons (Nycticorax nycticorax) of the New York Harbor estuary. AB - Blood samples from 145 Black-crowned Night-heron (Nycticorax nycticorax, BCNH) chicks (mean age 3 weeks) were taken from four island colonies (Goose (2004), Canarsie Pol (2005), Hoffman (2004 and 2005) and North Brother (2004 and 2005)) in New York Harbor in 2004 and 2005 to establish baseline health reference ranges for this species and to compare health indices of birds reared on different islands. Packed cell volume (PCV) and total solids (TS) did not differ among islands in either year. Herons raised on Hoffman Island in 2004 had lower white blood cell count (WBC), and higher activities of creatine phosphokinase (CPK), lactate dehydrogenase (LDH), aspartate amino transferase (AST), higher concentrations of potassium (K) and phosphorous (PHOS) and lower liver derived proteins (TP, prealbumin, albumin, alpha 1 globulins, alpha 2 globulins, beta globulins and gamma globulins) compared to herons from Goose and North Brother Islands. These changes suggest compromised health in chicks reared on Hoffman Island in 2004. On Hoffman in 2005, these biochemical analytes did not differ from concentrations and enzyme activities measured from birds on other islands. Although no single etiology can explain these extensive changes, it is likely that exposure to contaminants at foraging sites used by birds nesting on Hoffman and/or changes in prey availability and abundance causing birds to forage in different locations between years, led to differences measured in blood-based health indices. Avian health assessments coupled with foraging ecology serve as an excellent method for evaluating ecosystem health of the New York Harbor estuary system. PMID- 17720575 TI - Myectomy versus anterior transposition for inferior oblique overaction. AB - BACKGROUND: Inferior oblique overaction can be either secondary (as a sequela of ipsilateral superior oblique palsy) or primary (commonly associated with horizontal strabismus). Superior oblique underaction often coexists with both primary and secondary inferior oblique overaction. This retrospective case series compares the efficacy of inferior oblique myectomy versus anterior transposition in improving inferior oblique overaction and superior oblique underaction in eyes with either primary or secondary inferior oblique overaction. METHODS: One hundred twenty eyes of 81 patients were included in this retrospective case series, of which 20 had anterior transposition of the inferior oblique and 100 eyes underwent myectomy. Inferior oblique myectomy was compared with inferior oblique anterior transposition in improving inferior oblique overaction and superior oblique underaction in each diagnostic subgroup. Postoperative outcome was qualitatively and quantitatively assessed. Fisher's exact test was used to compare the outcomes. The quantitative improvement of function in terms of inferior oblique overaction and superior oblique underaction was analyzed by regression analysis. RESULTS: When postoperative inferior oblique overaction was considered, there was no statistically significant difference between myectomy and anterior transposition in both primary and secondary inferior oblique overaction. Myectomy was superior to anterior transposition in improving superior oblique underaction in both primary inferior oblique overaction (OR = 0.14; 95% CI, 0.015-1.45; p = 0.056) and secondary inferior oblique overaction (OR = 0; 95% CI, 0-0.027; p < 0.001). The quantitative improvement of function showed a significant difference between procedures for superior oblique underaction (t test; p = 0.005; 95% CI, 0.25-1.3) but not inferior oblique overaction (t-test; p = 0.8; 95% CI, -0.67-0.54). CONCLUSIONS: This study demonstrates both inferior oblique myectomy and inferior oblique anterior transposition to be effective in correcting primary and secondary inferior oblique overaction. Myectomy is more effective in improving superior oblique underaction associated with both primary and secondary inferior oblique overaction. On this basis, we feel that inferior oblique myectomy has some advantage over anterior transposition in treating combined inferior oblique overaction and superior oblique underaction and can be considered the procedure of choice. PMID- 17720577 TI - Effect of maternal fat reserves on the fatty acid composition of sardine (Sardina pilchardus) oocytes. AB - We compared the fatty acid (FA) composition of the muscle and gonads of female Iberian sardines with hydrated oocytes collected during the 2002/03 spawning season off southern Portugal (November and February) and off western Portugal (February). Sardine condition and total FA concentration in the muscle decreased between the two sampling dates, while the gonadosomatic index was similar between samples. Total monounsaturated FA concentrations in sardine gonads were different for the three samples while saturated and polyunsaturated FA concentrations were similar. Significant linear relations were found between FA concentrations in female muscle and oocytes, including eicosapentaenoic acid (EPA; 20:5n-3) and arachidonic acid (AA; 20:4n-6), both being essential for normal larval development. The concentration of docosahexaenoic acid (DHA; 22:6n-3) in oocytes was independent on muscle concentration, probably resulting from its selective transfer to the oocytes. The EPA/DHA ratio was highly conserved in sardine tissues, while DHA/AA and EPA/AA ratios varied significantly between samples. These results indicate that the FA content of eggs produced by sardines varies throughout the spawning season, egg FA concentrations decreasing as females lose condition, and FA composition also shows spatial variability. Both types of variability may have a significant impact on egg quality, particularly on the amount of reserves available to larvae affecting their resistance to starvation, and the appropriate FA composition required for normal growth. PMID- 17720578 TI - Serotonin stimulates mouse skeletal muscle 6-phosphofructo-1-kinase through tyrosine-phosphorylation of the enzyme altering its intracellular localization. AB - Serotonin (5-HT) is a hormone implicated in the regulation of many physiological and pathological events. One of its most intriguing properties is the ability to up-regulate mitosis. Moreover, it has been shown that 5-HT stimulate glucose uptake on skeletal muscle, suggesting that 5-HT may regulate glucose metabolism of peripheric tissues. Here we demonstrate that 5-HT stimulates skeletal muscle 6 phosphofructo-1-kinase (PFK) activity in a dose-response manner, through 5-HT(2A) receptor subtype. Maximal activation of the enzyme (2.5-fold compared to control) is achieved in the presence of 25pM 5-HT, increasing both PFK maximal velocity and affinity for the substrate fructose-6-phosphate. These effects occur due to tyrosine phosphorylation of the enzyme that is 2-fold enhanced upon 5-HT stimulation of skeletal muscles preparation. Once 5-HT-induced tyrosine phosphorylation of PFK is prevented by genistein, a tyrosine kinase inhibitor, the hormone stimulatory effect on PFK is abrogated. Wortmannin, a phosphatidylinositol-3-kinase (PI3K) inhibitor, does not interfere on 5-HT induced stimulation of PFK, supporting that the observed effects are independent on insulin signaling pathway. Furthermore, 5-HT promotes the association of PFK to the muscle f-actin, suggesting that the hormone alters PFK intracellular distribution, favoring its association to the cytoskeleton. Altogether, our results support evidences that 5-HT augments skeletal muscle glucose consumption through stimulation of glycolysis key regulatory enzyme, PFK, throughout tyrosine phosphorylation and intracellular redistribution of the enzyme. PMID- 17720579 TI - Biotin deficiency affects both synthesis and degradation of pyruvate carboxylase in rat primary hepatocyte cultures. AB - Pyruvate carboxylase (PC) is a biotin-dependent enzyme that plays a crucial role in gluconeogenesis, lipogenesis, Krebs cycle anaplerosis and amino acid catabolism. Biotin deficiency reduces its mass besides its activity. Enzyme mass is the result of its cellular turnover, i.e., its rates of synthesis and degradation. We have now investigated, by a pulse and chase approach in cultured primary hepatocytes, the effects of biotin deficiency on these rates. Wistar rats were fed a biotin-deficient diet and the controls were fed the same diet supplemented with biotin; their biotin status was monitored measuring lymphocytes propionyl-CoA carboxylase activity and urinary 3-hydroxyisovaleric acid. After 6 7 weeks primary hepatocytes were cultured in biotin-deficient or complete DMEM. PC activity was determined by measuring the incorporation of (14)C-bicarbonate into acid-non-volatile products, and its mass by streptavidin Western blots. Its synthesis rate was estimated from [(35)S] methionine incorporation into anti-PC antibody immunoprecipitate. Its degradation rate was calculated from the loss of radioactivity from previously labeled hepatocytes, in a medium containing an excess of non-radioactive methionine. PC synthesis rate in biotin-deficient hepatocytes was approximately 4.5-fold lower than in the controls, and its degradation rate was 5.1-fold higher. Therefore, the decrement of PC mass during biotin deficiency results both from a decrease in its synthesis and an increase in its degradation rates. To our knowledge, this is the first instance where a mammalian enzyme cofactor is necessary to sustain both processes. PMID- 17720580 TI - [Stem cells of dental pulp]. AB - Any clinician dreams to obtain the regeneration of the destroyed organ for his patient. In the human being, the regeneration of complex structures is not possible, except the liver and the bone marrow, which can be regenerated because of the presence of adult stem cells in these tissues. The stem cells have two principal properties: they ensure their self-renewal and they have the ability to differentiate into several cellular types. Using specific markers allowing the identification of the stem cells in bone marrow, stem cells were observed in dental pulp tissues. Although the origin, the identification, and the localization of these stem cells of dental pulp remain under consideration, the optimism in research on stem cells permits to believe that the knowledge on dental stem cells will lead to their use in therapeutics. PMID- 17720581 TI - Changes in carbohydrate metabolism by triazole growth regulators in cassava (Manihot esculenta Crantz); effects on tuber production and quality. AB - We have evaluated the ability of two triazole growth regulators, viz. triadimefon (TDM) and hexaconazole (HEX), in the enhancement of tuber production and quality in cassava (Manihot esculenta Crantz) through their effects on carbohydrate metabolism. One litre of 20 mg(-1) TDM and 15 mg(-1) HEX solution per plant were used for the treatments and groundwater was given to control plants. Triazole treatments reduced plant height and leaf area, but increased fresh and dry weights. Plants treated with TDM showed an increased net assimilation rate, which is followed by HEX and control plants. Triazole compounds increased the relative growth rate of cassava after 200 DAP, i.e. in the phase of tuber enlargement. Triazole compounds increased the starch and other carbohydrate contents and carbohydrate metabolising enzyme activities. From the results of this study, it can be concluded that these triazoles can significantly enhance the tuber production and quality by affecting the starch metabolism, apart from their fungicidal properties. PMID- 17720582 TI - [Using physiological tests on the selection of cut roses' varieties]. AB - We have observed that the evolution of the senescence in vase can be appreciated by the measures of pH, conductivity, or osmolarity of the petal cell sap of a rose variety. We wanted to check whether these physiological tests could be used to select the post-harvest quality of varieties in process of evaluation. Whereas the measures of pH and osmolarity do not seem to be correlated with the flower's vase life, those of conductivity seem to be linked to it (r=-0.74). As far as the pH is concerned, when the correlation is tested on varieties grouped in colours (white, yellow and ochre; pink and red; multicoloured) and not on the whole mixed varieties, then the correlation seems to be satisfactory, being characterized by r coefficients between -0.78 and -0.91. PMID- 17720583 TI - [A prospective research on the hedgerow's 'source' function]. AB - In pear tree, Forficula auricularia and Forficula pubescens are considered as active predators of the pest Cacopsylla pyri, since that their dispersal characteristics are of crucial importance for biological control. We studied their movement using capture-mark-release-recapture techniques. The aim of this study was to underline a hedge effect as source of beneficials spreading through the orchard. Our results show that movements are mainly linked to the C. pyri fluctuations with a food specialisation for the two species when co-occurring. PMID- 17720584 TI - Calcium chloride effects on salinity-induced oxidative stress, proline metabolism and indole alkaloid accumulation in Catharanthus roseus. AB - Catharanthus roseus (L.) G. Don. plants were grown with NaCl and CaCl2 in order to study the effect of CaCl2 on NaCl-induced oxidative stress in terms of lipid peroxidation (TBARS content), H2O2 content, osmolyte concentration, proline (PRO) metabolizing enzymes, antioxidant enzyme activities, and indole alkaloid accumulation. The plants were treated with solutions of 80 mM NaCl, 80 mM NaCl with 5 mM CaCl2 and 5 mM CaCl2 alone. Groundwater was used for irrigation of control plants. Plants were uprooted randomly on 90 days after sowing (DAS). NaCl stressed plants showed increased TBARS, H2O2, glycine betaine (GB) and PRO contents, decreased proline oxidase (PROX) activity, and increased gamma-glutamyl kinase (gamma-GK) activity when compared to control. Addition of CaCl2 to NaCl stressed plants lowered the PRO concentration by increasing the level of PROX and decreasing the gamma-GK activities. Calcium ions increased the GB contents. CaCl2 appears to confer greater osmoprotection by the additive role with NaCl in GB accumulation. The antioxidant enzymes superoxide dismutase (SOD), peroxidase (POX) and catalase (CAT) were increased under salinity and further enhanced due to CaCl2 treatment. The NaCl-with-CaCl2-treated C. roseus plants showed an increase in total indole alkaloid content in shoots and roots when compared to NaCl-treated and untreated plants. PMID- 17720585 TI - Introducing water frogs--is there a risk for indigenous species in France? AB - The ecological success of introduced species in their new environments is difficult to predict. Recently, the water frog species Rana ridibunda has raised interest, as different genetic lineages were introduced to various European countries. The aim of the present study was to analyze the potential invasiveness of R. ridibunda and assess the risk of replacement for indigenous water frog species. The investigation of over 700 water frogs from 22 locations in southern France and four locations in Spain shows that the competition with indigenous species is mainly limited to a particular habitat type, characterized by high oxygen and low-salinity freshwater. The competitive strength of R. ridibunda may be related to a higher growth rate and longevity as compared to the indigenous species R. grafi and R. perezi. Our data suggest that R. ridibunda is a risk to the diversity of indigenous water frog assemblages in France. Future monitoring needs to clarify the distribution of R. ridibunda, its ecological niche, and the risk status for indigenous water frog species. PMID- 17720586 TI - Fire as a control agent of demographic structure and plant performance of a rare Mediterranean endemic geophyte. AB - We examine the effects of fire and/or surrounding vegetation cover on demographic stage densities and plant performance for a rare endemic geophyte, Acis nicaeensis (Alliaceae), in Mediterranean xerophytic grasslands of the 'Alpes Maritimes' French 'departement', through sampling plots in unburned and burned treatments. Fire increases density of flowering individuals and seedling emergence, as well as clump densities and number of individuals per clump, per limiting vegetation height and cover, and increasing bare soil cover. In contrast, fire has no effect on reproductive success. Nevertheless, two growing seasons after fire, all parameters of demographic stages and plant performance do not significantly differ between the two treatments. Small-scale fire is beneficial for the regeneration of this threatened geophyte at a short-time scale. In this context, a conservation planning with small and controlled fires could maintain the regeneration window for populations of rare Mediterranean geophytes. PMID- 17720587 TI - The predatory behavior of Pheidole megacephala. AB - We studied the foraging and predatory behaviors of the invasive African myrmicine ant, Pheidole megacephala (F.) in its native range. Workers can singly capture a wide range of insects, including relatively large prey items. For still larger prey, they recruit at short range those nestmates situated within reach of an alarm pheromone and together spread-eagle the insect. These behaviors are complimented by a long-range recruitment (of nestmates remaining in the nest) based on prey size. P. megacephala scouts also use long-range recruitment when they detect the landmarks of termites and competing ant species, thus permitting them to avoid confronting these termites and ants solitarily. PMID- 17720588 TI - Comparison of the ability of feline calicivirus (FCV) vaccines to neutralise a panel of current UK FCV isolates. AB - Feline calicivirus (FCV) comprises a large number of strains which are related antigenically to varying degrees. The antigenic variability creates problems for choosing antigens to include in vaccines. Historically, these have been selected for use based on their cross-reactivity with a high proportion of field strains. However, it is important to determine the current level of cross-reactivity of vaccines and whether or not this may be decreasing owing to widespread vaccine use. In this in vitro study, we have compared the ability of antisera to two vaccine viruses (FCV strain F9 and FCV strain 255) to neutralise a panel of 40 recent UK field isolates. These 40 isolates were obtained by randomised, cross sectional sampling of veterinary practices in different geographical regions of the UK so as to ensure they were representative of viruses circulating in the veterinary-visiting population of cats in the UK. Virus neutralisation assays showed that both vaccine strains are still broadly cross-reactive, with F9 antiserum neutralising 87.5% and 255 antiserum 75% of isolates tested with antiserum dilutions of 1 in 2 or greater. However, when antibody units were used, in order to take account of differences in homologous titres between antisera, fewer isolates were neutralised, with F9 antiserum showing a slightly higher proportion of isolates neutralised than 255. Multivariable analysis of the sample population of 1206 cats from which the 40 isolates were derived found that vaccinated cats were at a decreased risk of being positive for FCV, whereas cats from households with more than one cat, and cats with mouth ulcers were at increased risk. In addition as cats became older their risk of shedding FCV decreased. PMID- 17720589 TI - Changing times: DNA resequencing and the "nearly normal autopsy". AB - No matter how meticulous the autopsy, non-traumatic deaths in the young go unexplained from 5-10% of the time. The percentage is higher in children and young adults. Advances in molecular biology and DNA technology now make it possible to explain many of those deaths. This development is not without irony. At the same time that many clinicians are expressing frustration about the lack of tangible gains provided by the Human Genome Project [Greenhalgh T. The Human Genome Project. J R Soc Med. Dec 2005;98(12):545], and pathologists are wondering about the viability of their field, DNA technology is about to reshape the field of forensic pathology. Emerging evidence suggests that the underlying cause of death in many is genetic, and that both the heart and liver abnormalities can both play a role. The problem is that death from a wide variety of genetic defects may leave no histological markers. The ability to identify these "invisible diseases" with postmortem genetic testing has become a reality far more quickly than anyone had ever imagined. The US Food and Drug Administration is about to place "black box" warnings on warfarin advising doctors screen potential recipients for the ability to metabolize that drug and the American Heart Association has recently editorialized that because of genetic-induced variations in electrical conduction that all newborns should have a screening electrocardiogram before they leave the hospital. The introduction of large-scale genetic screening will have an enormous effect on the practice of forensic pathology, far beyond anything seen in our lifetimes. It will also change the practice of medicine as we know it. This paper reviews the current status of the problem. PMID- 17720590 TI - Alcohol concentration and carbonation of drinks: the effect on blood alcohol levels. AB - Alcohol absorption and elimination vary considerably amongst individuals, and are subject to influences from a variety of factors. The effects of alcohol concentration and beverage mixer type on the rate of alcohol absorption, in a controlled environment was studied. 21 subjects (12 male, 9 female) consumed a solution containing alcohol, on three separate occasions. The three solutions were, A: Neat vodka (37.5 vol%), B: Vodka mixed with still water (18.75 vol%), C: Vodka mixed with carbonated water (18.75 vol%). The volume of alcohol each subject consumed was determined by Widmark's equation. The alcohol was drunk in a 5 min period following an overnight fast and breath alcohol concentrations were measured over a 4h period using a breathalyser. 20/21 subjects absorbed the dilute alcohol at a faster rate than the concentrated alcohol. The difference between the absorption rates was found to be significant (p<0.001). The use of a carbonated mixer had varying effects on the alcohol absorption rate. 14/21 subjects absorbed the alcohol with the carbonated mixer at a faster rate, with 7 subjects showing either no change or a decrease in rate. The mean absorption rate for solution C was 4.39+/-0.45 (mg/100ml/min), and the difference between this absorption rate and that with the still mixer (1.08+0.36) was significant (p=0.006). PMID- 17720591 TI - Suicidal hanging: fatalities in Istanbul retrospective analysis of 761 autopsy cases. AB - We retrospectively analyzed the autopsy records of the Institute of Forensic Medicine during the five-year period between 1998 and 2002 to document the characteristics of fatalities resulting from hanging which is the commonest mode of suicide in Istanbul. Upon analysis of death scene investigation and autopsy reports together with the information gathered from the police, the cases of hanging fatalities of suicidal origin were selected. Seven hundred sixty one hanging cases of suicidal origin were detected and evaluated in terms of demographic features, the type of hanging material used for ligature, cause of death, internal findings in neck organs, other traumatic findings suggesting the use of another method for suicide, toxicological findings and microscopic findings in delayed death cases. In 364 of these cases suspension was complete and in 397 incomplete. Five hundred thirty seven of those (70.56%) were male and 224 (29.44%) were female. The preponderance of male cases in our autopsy population was also detected in suicidal hanging cases. There was no case aged lower 10 and the number of the cases in the age group of cases aged over 80 was the lowest (n=3, 0.4%). In 634 of cases, the place of hanging was the subject's own house, most victims selected rope (652 cases) for the ligature with the rest using sheet, belt, cable and necktie. There were traumatic findings showing attempts of suicide other than hanging in 24 cases (tentative marks in 22 cases and non-fatal burning in 2). In 23 of cases, there were bruises of different ages. In these cases females constituted the majority suggesting violence against women that is a social problem in various cultural subgroups of our country. This violence may have played a role in the decision of suicide. Superficial bruises were detected in 56 cases and were attributed to the trauma. Fractures in neck organs were detected in 446 of cases. In fracture-determined cases, fracture in hyoid bone was seen in 177, in thyroid cartilage in 163, in both hyoid and thyroid in 106. Vertebral fracture was detected in six cases and fractures both in hyoid, thyroid and vertebra was found in four cases. Hyperemic lines around the ligature were prominent in 620 of the cases and soft tissue ecchymoses in all cases. In 305 of the cases (40.07%) diagnosis was based only on the soft tissue hemorrhage. PMID- 17720592 TI - Epidemiology of drowning in Mangalore, a coastal Taluk of South India. AB - Drowning is a major global public health problem which is amenable to prevention. According to the Global Burden of Diseases 2000 data, the number of deaths caused due to drowning is 449,000 people worldwide (7.4 per 100,000 population). The aim of this study is to derive a profile of drowning victims, to identify the successful drowning preventive measures that may be adopted or enhanced in Mangalore, a coastal Taluk of South India. Retrospective study of deaths caused due to drowning in an 11 years period between 1994 and 2005 was done by reviewing the medical records, the findings of which have been described later. Epidemiologic profiles of populations at risk and the contributing factors are highlighted while public safety measures are recommended. PMID- 17720593 TI - Interpretation of lesions of the cardiac conduction system in cocaine-related fatalities. AB - This study examines cases of chronic drug users who died suddenly after drug administration. Victims were young subjects, aged from 19 to 35 from Switzerland and known to the police as long-term drug users. The circumstances of death suggested the occurrence of a sudden, unexpected death. Some victims were undergoing methadone treatment. In each case, a forensic autopsy and toxicological analyses were performed at the Institute of Forensic Medicine in Lausanne in Switzerland between 2002 and 2004, including hair analysis as a means to establish chronic drug use in general, and cocaine use in particular. The conduction system was examined histologically and cases showing potentially lethal changes were chosen for this report. The most frequent lesions found were severe thickening of the atrioventricular node artery, intranodal and perinodal fibrosis, and microscopic foci of chronic inflammatory infiltration. The authors conclude that pathological lesions in the conduction tissue may play a role in the occurrence of death attributed to intoxication consecutive to cocaine ingestion. PMID- 17720595 TI - Sexing of human hip bones of Indian origin by discriminant function analysis. AB - The present study was carried out in terms of discriminant analysis and was conducted on 100 human hip bones (of unknown sex) of Indian origin. Based on morphological features, each of the hip bone was rated on a scale of 1-3 for sexing. Twelve measurements and five indices were recorded. The results of discriminant function analysis showed that the acetabular height (vertical diameter) and indices 1 (total pelvic height/acetabular height), 2 (midpubic width/acetabular height) and 3 (pubic length/acetabular height) were very good measures for discriminating sexes. Pelvic brim depth, minimum width of ischiopubic ramus and indices 4 (pelvic brim chord x pelvic brim depth) and 5 (pubic length x 100/ischial length) were also good discriminators of sex. The remaining parameters were not significant as they showed a lot of overlap between male and female categories. The results indicated that one exclusive criterion for sexing was index 3 (pubic length/acetabular height). In comparison with the morphological criteria, the abovementioned index caused 25% and 10.25% increase in the hip bones of female and male category, respectively. PMID- 17720594 TI - Aggression and violence towards health care providers--a problem in Turkey? AB - Health care providers are increasingly concerned about the escalating incidence of verbal and physical abuse to healthcare staff. Factors, such as long wait in hospital areas, which lead to client frustration over an inability to obtain needed services promptly, are influencing these situations. Nonetheless, incidents of this nature can cause immense psychological harm as well as physical damage among medical employees. The current study aimed to ascertain from staff members aggressive experiences in the workplace, and the effects on the individual. The results of this study mirrored those of similar surveys in Turkey. Non-reporting was revealed as a major problem. Respondents believed they were treated less seriously than similar incidents involving private citizens. Accordingly, staff criticized hospital managers, the police, and the courts for their attitude about assaults towards hospital employees. They reported feeling vulnerable to abuse and there was a general desire for training in preventing and protection. These include teaching staff breakaway techniques, increasing the number of trained security officers on duty, issuing personal alarms, and encouraging staff to officially report all incidents. PMID- 17720596 TI - Arteriocolic fistulae due to a stab wound: a rare cause of lethal lower gastrointestinal bleeding. AB - The authors describe the first reported case of lethal lower gastrointestinal bleeding due to an iliocolic fistulae following a single stab wound. They also discuss the pathophysiology of the enterovacscular fistulae, as well as a review of the literature and assess forensic characteristics. This unusual case underlines the importance of being aware of the victim's history in arteriocolic fistulae due to a stab wound. PMID- 17720597 TI - Spontaneous rupture of splenic vein in a pregnant woman during a religious ritual. AB - The treatment of retroperitoneal hemorrhage can be by surgical or a conservative approach but the main problems about these cases are difficulty in diagnosis due to negative results after abdominal lavage and the difficulties in accessing the retroperitoneal area surgically. Retroperitoneal hemorrhage during pregnancy, occurring as a result of spontaneous rupture, is very rare event. Such cases require urgent operation and if not, result in high mortality. A twenty-eight year old pregnant woman was admitted to the hospital dead after collapsing at home during a religious ritual. No systemic or gynecological pathology had been diagnosed. No traumatic injury on her body was found at early postmortem examination. The pathologic findings found at the autopsy are; approximately 2.5 L of coagulated blood in the retroperitoneal region and 10-12 cm of haematoma at the hilum of spleen; dissection revealed a tear of 0.5 cm on lienal vein at a point 3 cm from the hilum. Surgical approach is the most important procedure for diagnosis and therapy of the bleeding. Autopsy may be only diagnostic technique in the case of retroperitoneal hemorrhage death when the death is so rapid that there is no time to intervene surgically. PMID- 17720598 TI - A fatal case of pontine hemorrhage related to methamphetamine abuse. AB - In this report, we describe a fatal case of pontine hemorrhage related with methamphetamine abuse. A 54-year-old male was found dead in a prone position in his parents' house, and a medico-legal autopsy was carried out to determine the cause of his death. Externally, although an injection mark-like injury with subcutaneous hemorrhage was observed in the left cubital fossa, the autopsy revealed no severe trauma leading to death. Internally, every organ was moderately congested. The brain weighed 1330 g. Macroscopically, there was no vascular abnormality such as aneurysm or malformation. In the sections of the brain stem, a massive hematoma occupied the central area of the pons. Drug screening test using Triage was weakly positive for amphetamines. Moreover, in the blood and urine samples, methamphetamine was quantitatively detected at concentrations of 0.4 and 0.6 mg/l, respectively, by gas chromatography-mass spectrometry. Other drugs and poison were not detected in the blood and urine samples collected at autopsy. Histopathologically, necrotizing angiitis characterized by fibrinoid necrosis of the intima and media was observed with cell infiltration. Thus, the pontine hemorrhage seemingly resulted from methamphetamine-induced angiitis, with an acute elevation of blood pressure after methamphetamine abuse. PMID- 17720599 TI - Efficacy of accelerated hepatitis B vaccination program in patients being actively treated for hematologic malignancies. AB - BACKGROUND: The goal of this study was to conduct an accelerated vaccination program and to determine its efficacy in patients susceptible to hepatitis B virus (HBV) receiving chemotherapy because of their hematologic malignancies. METHODS: Over a one-year period, a total of 327 patients who were diagnosed as having a hematologic malignancy were serologically analyzed in terms of HBV infection. Of those found to be susceptible to HBV infection, a total of 42 patients consisting of 16 females and 26 males were enrolled in the accelerated vaccination program. All the patients were administered a 20-microg yeast-derived recombinant hepatitis B vaccine on days 0, 14, and 28. Anti-HBs titers above 10IU/l at 1 and 3 months after the final dose were accepted as protective. RESULTS: A total of 146 (44.6%) patients were susceptible to HBV, while 13 (4.0%) were carriers, 28 (8.6%) were vaccinated, and 113 (34.5%) had had a previous HBV infection. A total of 42 patients (16 females and 26 males, mean age 34.5+/-10.9 years) were enrolled in the vaccination program. Overall, 23.8% (10/42) of the patients in the program had developed anti-HBs at one month after the last vaccination. CONCLUSIONS: Poor results obtained by different vaccination programs suggest the need for alternative strategies to prevent the disease. PMID- 17720600 TI - Severe respiratory disease and its relationship with respiratory viruses in Colombia. AB - BACKGROUND: There are important gaps in our understanding of the epidemiology of respiratory virus infections in tropical countries. In September 2003, the Colombian epidemiological surveillance system was notified of several deaths from an acute respiratory disease (ARD). METHODS: In order to identify the agents associated with ARD cases, a clinical and laboratory-based surveillance system was implemented throughout the country. RESULTS: Between September 19 and December 31, 2003, 64 suspected cases of ARD were reported; of these reported cases, 21 (33%) died. Among 25 patients who underwent virus studies, influenza A (H3N2) (n=7) was the most frequently identified agent. Other viruses included parainfluenza (4), influenza B (1), and respiratory syncytial virus (3). The peak occurrence of cases and deaths coincided with the replacement of the influenza A (H3N2) Panama strain, which had been circulating in Colombia since 1999, by three new influenza A (H3N2) strains (Korea, Fujian, and Wyoming). CONCLUSIONS: This outbreak led to the strengthening of surveillance for respiratory viruses and to new national recommendations for influenza vaccination in Colombia. PMID- 17720601 TI - Human listeriosis and animal models. AB - Human listeriosis is a potentially fatal foodborne infection caused by Listeria monocytogenes, an opportunistic psychrophile bacterium that is widespread in the environment. It has only recently emerged as a significant cause of human infection in industrialized countries, owing to appearance of a vulnerable population of immunocompromised individuals, and the concomitant development of large-scale agro-industrial plants and refrigerated food. Here we review the main clinical features of human listeriosis and highlight specificities and similarities with animal listeriosis in diverse species. Finally, we present some of the critical determinants for the choice of an appropriate animal model to study human listeriosis. PMID- 17720602 TI - The epidemiology of human listeriosis. AB - Listeriosis is a serious invasive disease that primarily afflicts pregnant women, neonates and immunocompromised adults. The causative organism, Listeria monocytogenes, is primarily transmitted to humans through contaminated foods. Outbreaks of listeriosis have been reported in North America, Europe and Japan. Soft cheeses made from raw milk and ready-to-eat meats are high risk foods for susceptible individuals. Efforts by food processors and food regulatory agencies to aggressively control L. monocytogenes in the high risk foods have resulted in significant decreases in the incidence of sporadic listeriosis. PMID- 17720603 TI - Listeriolysin O: a phagosome-specific lysin. AB - Listeriolysin O (LLO) is a pore-forming toxin of the cholesterol-dependent cytolysin family and a primary virulence factor of the gram-positive, facultative intracellular pathogen Listeria monocytogenes. During the intracellular life cycle of L. monocytogenes, LLO is largely responsible for mediating rupture of the phagosomal membrane, thereby allowing the bacterium access to the host cytosol, its replicative niche. In the host cytosol, LLO activity is controlled at numerous levels to prevent perforation of the plasma membrane and loss of the intracellular environment. In this review, we focus primarily on the role of LLO in phagosomal escape and the multiple regulatory mechanisms that control LLO activity in the host cytosol. PMID- 17720605 TI - Estimation of the time of death of decomposed or skeletonized bodies found outdoors in cold season in Sapporo city, located in the northern district of Japan. AB - In Sapporo city, located in the northern district of Japan, it is very difficult to estimate the time of death of decomposed or skeletonized bodies found outdoors in cold season (November-April) because postmortem changes are markedly retarded in the season compared with warm season (May-October), and the bodies are often damaged and skeletonized by carnivorous animals such as wild dogs and foxes. However, they cannot damage the brain in the cranium. The brain is mainly damaged by fly larvae. In Sapporo city, we can estimate that the time of death of a cadaver found outdoors in the cold season is in the beginning of November or before if fly larvae hatched in autumn exist on the cadaver, and that the time of death is in the beginning of November or after if fly larvae hatched in autumn do not exist and most of the brain remains in the cranium. PMID- 17720604 TI - Analysis of oseltamivir active metabolite, oseltamivir carboxylate, in biological materials by HPLC-UV in a case of death following ingestion of Tamiflu. AB - An HPLC-UV method was established for determination of oseltamivir carboxylate, an active metabolite of oseltamivir, in biological materials. Oseltamivir carboxylate and floropipamide (internal standard) were extracted by using a mixed mode cation exchange extraction cartridge. The recovery yields of oseltamivir carboxylate from spiked blood at concentrations 0.1microg/ml and 1.0microg/ml were 103.8+/-16.9% and 95.0+/-4.3%, respectively. Linearity was obtained in the concentration from 0.1 to 3.0microg/ml. The detection limit was 0.04microg/ml (S/N=3). This method was applied to a case of death from falling after ingestion of a Tamiflu capsule containing 75mg of oseltamivir. Concentration of oseltamivir carboxylate in the femoral blood was 0.4microg/ml. The highest concentration in all specimens was in the liver at 18.3microg/g. In all brain samples, the concentrations were not higher than the quantification limit (0.1microg/g). PMID- 17720606 TI - The golden gene (SLC24A5) differentiates US sub-populations within the ethnically admixed Y-SNP haplogroups. AB - Y-SNPs are currently being investigated for their potential to predict the ethnogeographic origin of the donor of a crime scene sample. Unfortunately, due to the presence of genetically admixed individuals within ethnic sub-populations within a particular haplogroup (hg), it is sometimes difficult to predict the ethnogeographic ancestry of an individual using only Y-SNPs. In the present work we determine the feasibility of using a combination of the golden pigmentation gene (SLC24A5) SNP and recently described high resolution Y-SNP markers to distinguish some of the different ethnic groups within particular Y-SNP hgs. Four hundred twenty-four individuals (128 African, 206 European, 50 Hispanic/Latin, 20 Pakistan, 20 E.Asian/Indian) were typed for a SNP within the golden gene. The Y SNP hg was determined for all males and it was found that many of the European derived hg possessed a significant amount of ethnic admixture, with R1b3 having the most. We show the use of the golden gene, in combination with more informative Y-SNPs (U152, U106, and M222) and those that define the major hg, can differentiate between most of the African vs. European and African vs. E. Asian members of these heterogeneous populations. PMID- 17720608 TI - Post-hypoxic animal model of myoclonus. AB - Post-hypoxic myoclonus is a form of myoclonus frequently caused by cardiac arrest. Development of an animal model may facilitate understanding of the condition and its treatments. We describe an animal model of post-hypoxic myoclonus developed in our laboratory through cardiac arrest, initially induced by chemical and later by mechanical obstruction of major cardiac vessels. These animals respond to valproate, clonazepam and 5-hydroxytrytophan reminiscent of its human counterpart. We review their behavioral, pharmacological and neuropathological features. Therapy developed for myoclonus in this model may be helpful for myoclonus from other etiologies such as corticobasal degeneration, Lewy-body disorders, Creutzfeld-Jacob disease, Alzheimer's disease. PMID- 17720607 TI - Treatment of nano-sized rutile phase TiO2 powder under ultrasonic irradiation in hydrogen peroxide solution and investigation of its sonocatalytic activity. AB - The treated mixed-crystal TiO(2) powder with high sonocatalytic activity was obtained through utilizing ultrasonic irradiation in hydrogen peroxide solution. At the same time, some influencing factors (including heat-treated temperature and heat-treated time) on the sonocatalytic activity of treated mixed-crystal TiO(2) powder were also considered through the degradation of methylene blue in aqueous solution. In this work, it was found that the sonocatalytic degradation ratio of methylene blue in the presence of treated mixed-crystal TiO(2) powder was much higher than ones in the presence of nano-sized rutile phase TiO(2) powder and with onefold ultrasonic irradiation. At last, the methylene blue in aqueous solution was completely degraded and became some simple inorganic anions such as NO(3)(-), SO(4)(2-) and Cl(-). All experiments indicated that the sonocatalytic method adopting treated mixed-crystal TiO(2) powder as sonocatalyst was an advisable choice for the treatments of non- or low-transparent wastewaters in future. PMID- 17720609 TI - Training the cervical muscles with prescribed motor tasks does not change muscle activation during a functional activity. AB - Both low-load and high-load training of the cervical muscles have been shown to reduce neck pain and change parameters of muscle function directly related to the exercise performed. The purpose of this study was to investigate whether either training regime changes muscle activation during a functional task which is known to be affected in people with neck pain and is not directly related to either exercise protocol. Fifty-eight female patients with chronic neck pain were randomised into one of two 6-week exercise intervention groups: an endurance strength training regime for the cervical flexor muscles or low-load training of the cranio-cervical flexor muscles. The primary outcome was a change in electromyographic (EMG) amplitude of the sternocleidomastoid (SCM) muscle during a functional, repetitive upper limb task. At the 7th week follow-up assessment both intervention groups demonstrated a reduction in their average intensity of pain (P<0.05). However, neither training group demonstrated a change in SCM EMG amplitude during the functional task (P>0.05). The results demonstrate that training the cervical muscles with a prescribed motor task may not automatically result in improved muscle activation during a functional activity, despite a reduction in neck pain. PMID- 17720610 TI - Towards the molecular basis of heterosis. AB - Heterosis describes the superior performance of heterozygous hybrid plants over their homozygous parental inbred lines. Despite the rediscovery of this phenomenon a century ago and its paramount agronomic importance, the genetic and molecular basis of heterosis remains enigmatic. Recently, various pioneer studies described differences in genome organization and gene expression of hybrids and their parental inbred lines. At the genomic level, a significant loss of colinearity at many loci between different inbred lines of maize was observed. At the level of gene expression, complex transcriptional networks specific for different developmental stages and tissues were monitored in maize (Zea mays), rice (Oryza sativa) and Arabidopsis (Arabidopsis thaliana). Integration of this complex expression data might contribute to improve our understanding of the molecular basis of heterosis. PMID- 17720611 TI - Quantitative vertebral morphometry using neighbor-conditional shape models. AB - A novel method for vertebral fracture quantification from X-ray images is presented. Using pairwise conditional shape models trained on a set of healthy spines, the most likely normal vertebra shapes are estimated conditional on the shapes of all other vertebrae in the image. The difference between the true shape and the reconstructed normal shape is subsequently used as a measure of abnormality. In contrast with the current (semi-)quantitative grading strategies this method takes the full shape into account, it develops a patient-specific reference by combining population-based information on biological variation in vertebral shape and vertebra interrelations, and it provides a continuous measure of deformity. The method is demonstrated on 282 lateral spine radiographs with in total 93 fractures. Vertebral fracture detection is shown to be in good agreement with semi-quantitative scoring by experienced radiologists and is superior to the performance of shape models alone. PMID- 17720612 TI - International Consortium on Head and Neck Cancer Awareness (ICOHANCA). PMID- 17720613 TI - Sumoylation, a post-translational regulatory process in plants. AB - The reversible conjugation of the small ubiquitin-related modifier (SUMO) peptide to protein substrates (sumoylation) is emerging as a major post-translational regulatory process in animals and other eukaryotes, including plants. Database annotation, and genetic and biochemical analyses indicate that components of the SUMO conjugation and deconjugation systems are conserved in plants such as Arabidopsis, rice, tomato, and Medicago. Specifically, Arabidopsis AtSUMO1/2 and SUMO E2 conjugation enzyme AtSCE1a are implicated in abscisic acid (ABA) responses and the ubiquitin-like SUMO protease 1 (ULP1) AtESD4 in flowering time regulation. The AtSIZ1 SUMO E3 ligase functions in phosphate starvation responses, cold tolerance, basal thermotolerance, salicylic acid (SA)-dependent pathogen defense, and flowering time regulation. Following is a brief overview of the current understanding of SUMO conjugation and deconjugation determinants, and biological processes that are regulated in plants. PMID- 17720614 TI - The evolution of plant regulatory networks: what Arabidopsis cannot say for itself. AB - Genetic and molecular analyses in the dicot model plant Arabidopsis thaliana have begun to shed some light on regulatory networks in plants. However, comparisons with other species are necessary to validate networks identified in model species on the evolutionary scale. Many key regulatory proteins are encoded by members of transcription factor gene families. Orthologous genes can be identified by phylogenetic reconstructions based on conserved protein domains and functionally substantiated by gene expression patterns and mutant analyses. Recent comparative analyses of different pathways involved in shoot meristem development reveal not only conservation from basal land plants to angiosperms but also evolutionary freedom for significant adaptations in the course of plant speciation. PMID- 17720615 TI - Mechanisms of auxin-dependent cell and tissue polarity. AB - The establishment of cellular asymmetries and their coordination within the tissue layer are fundamental to the development of multicellular organisms. In plants, the induction and coordination of cell polarity have classically been attributed to involve the hormone auxin and its flow. However, the underlying mechanisms have only recently been addressed at the molecular level. We review progress on the characterisation of the auxin influx and efflux carrier properties of specific plasma membrane proteins, mechanisms underlying their delivery to and internalisation from the plasma membrane, their endocytic transport and degradation. We discuss mechanisms of auxin gradient, transport and response action during the coordination of polarity, along with the downstream involvement of Rho-of-plant small GTPases during the execution of cell polarity. PMID- 17720617 TI - Biodirected mutagenic chemical assay of PM(10) extractable organic matter in Southwest Mexico City. AB - The concentration of breathable particles (PM(10)) in urban areas has been associated with increases in morbidity and mortality of the exposed populations, therein the importance of this study. Organic compounds adsorbed to PM(10) are related to the increased risk to human health. Although some studies have shown the lack of correlation between specific mutagenic compounds in an organic complex mixture (OCM) and the mutagenic response in several bioassays, the same organic compounds selectively separated in less complex groups can show higher or lower mutagenic responses than in the OCM. In this study, we fractionated the OCM, from the PM(10) in four organic fractions of increasing polarity (F1-F4). The Salmonella bioassay with plate incorporation was applied for each one using TA98, with and without S9 (mammalian metabolic activation), and YG1021 (without S9) strains. The most polar fraction (F4) contained the greatest mass followed by F1 (non-polar), F2 and F3 (moderately polar). The concentrations of the OCM as well as the F4 were the only variables correlated with PM(10), atmospheric thermal inversions, fire-prone area, NO(2), SO(2), CO, rain and relative humidity. This indicated that polar organic compounds were originated in gas precursors formed during the atmospheric thermal inversions as well as the product of the incomplete combustion of vehicular exhausts and of burned vegetation. The percentages of the total PAH, and the individual PAH with molecular weight > or = 228 g mol(-1) (except retene) correlated with the percentages of indirect-acting mutagenicity in TA98+S9. The percentages of the total nitro-PAH and most of the analyzed individual nitro-PAH correlated with percentages of the direct-acting mutagenicity in both TA98-S9 and YG1021, the latter being more sensitive. In general, the highest mutagenic activity (indirect and direct) was found in F3 (moderately polar) and in F4 (polar). The non-polar fraction (F1) did not exhibit any kind of mutagenicity. In 77% of the cases, mutagenic activity was higher in the sum fractions with respect to their OCM. The combinations between F1, F2 and F4, with F3 under different or equal proportions suggested that mutagenicity reduction, in the combined matter of January (with TA98+S9 and YG1021) and of May (with YG1021), was due to concentrations of mutagens and non-mutagens in each fraction, and not to an antimutagenic effect. The organic compounds present in the non-polar fractions showed no antagonism, inhibition or reduction in the most mutagenic fractions in both indirect- and direct-acting mutagenicity, and the less polar organic compounds in F3 reduced mutagenicity in F4, in both months. PMID- 17720616 TI - Effects of 1,4-phenylenebis(methylene)selenocyanate on mutagenesis and p53 protein expression in the tongue of lacI rats treated with 4-nitroquinoline-N oxide. AB - Previously we showed that the organoselenium compound, 1,4 phenylenebis(methylene)selenocyanate (p-XSC)(1) inhibits 4-nitroquinoline-N-oxide (4-NQO)-induced tongue tumorigenesis in Fisher rats. Here we investigate possible mechanisms of this inhibition by monitoring mutagenesis and p53 protein levels in lacI and conventional Fisher rats treated with: (1) a carcinogenic dose of 4-NQO for 10 weeks in drinking water, (2) 4-NQO+p-XSC (15 ppm as selenium), and (3) 4 NQO followed by p-XSC. For mutagenesis studies, rats were euthanized at 7, 12 or 23 weeks after the start of 4-NQO. For studies on p53 levels, rats were euthanized at 11, 15 and 23 weeks. Appropriate controls were also monitored. In the 4-NQO-alone groups, the mutant fraction (MF) in the cII gene in tongue increased at least 50x background level. The MF (in units of mutants/10(5) plaque forming units) for the 7, 12, and 23 weeks 4-NQO groups were respectively, 184 +/ 88, 237 +/- 105, and 329 +/- 110. Thus, mutagenesis increased with length of exposure and post-treatment time. p-XSC modestly (ca. 15-30%) inhibited mutagenesis under all conditions. The inhibition reached significance at the last time point. When p-XSC was administered after 4-NQO, the MF was also modestly reduced. In 4-NQO-alone animals, levels of p53 in tongue (determined by Western blotting) were 1, 1.5 and 2.4 control levels at 10, 15 and 23 weeks, respectively. In the p-XSC+4-NQO group, the enhancement in p53 levels by 4-NQO treatment was decreased about 90% at 15 weeks and 45% (P<0.05) at 23 weeks, and by slightly smaller percentages in corresponding post-treatment groups. p-XSC alone did not alter p53 levels. As p53 levels generally increase in response to DNA damage, these results suggest that p-XSC reduces 4-NQO-induced DNA damage, resulting in reduced 4-NQO-induced mutagenesis and carcinogenesis. However, the fact that p-XSC is also effective when administered after 4-NQO, suggests additional mechanisms of inhibition exist. PMID- 17720618 TI - A Raman, infrared and XRD analysis of the instability in volcanic opals from Mexico. AB - A series of natural volcanic opal samples with the destabilization phenomena from Mexican deposits (states of Queretaro and Jalisco) was investigated by Raman microprobe (RMP), infrared spectrometry and XRD analysis. These techniques show that at low and room temperatures the unaltered transparent opals may be transformed into destabilized white opals, which are a mixture of different polymorphs of tridymite and alpha-cristobalite with various degrees of crystallinity. We found systematic changes in frequencies of both the Raman and the infrared bands, caused by increasing regularities of bond-lengths and bond angles Si-O-Si groups under the effect of stability. Micro-Raman spectrometry confirms that in the destabilized opal the principal mineral phases are MC (monoclinic ordered)- and MX (incommensurate monoclinic)-tridymites that are characterized by more structural order in comparison with other structural modification of this phase in unaltered opal (POn pseudo-orthorhombic disordered tridymite). XRD investigations show that in the sequence from unaltered to destabilized opal the position of principal maximum (4.30, 4.10 and 2.50 A) shifts towards higher d-spacing. This XRD shifting to higher d-spacing can largely be explained by an increasing amount of tridymite stacking and unresolved superposition of cristobalite and tridymite reflections. The destabilization phenomena in volcanic opals is due to the structural ordering/disordering that is characterized mainly by the formation of the different tridymite polymorphs (MC and MX) in the destabilized opal-CT as well as the decreasing content of molecular water in the structure. PMID- 17720619 TI - Spectral and structural studies of copper(II) complexes of thiosemicarbazones derived from salicylaldehyde and containing ring incorporated at N(4)-position. AB - Mononuclear and binuclear copper(II) complexes (1-8) with two ONS donor thiosemicarbazone ligands {salicylaldehyde 3-hexamethyleneiminyl thiosemicarbazone [H2L1] and salicylaldehyde 3-tetramethyleneiminyl thiosemicarbazone [H2L2]} have been prepared and physico-chemically characterized. IR, electronic and EPR spectra of the complexes have been obtained. The thiosemicarbazones bind to metal as dianionic ONS donor ligands in all the complexes except in [Cu(HL1)2] (2) and [Cu(HL2)2] (6). In compounds 2 and 6 the ligands are coordinated as monoanionic HL- ones. The magnetic susceptibility measurements indicate that all the complexes are paramagnetic. In complex [(CuL1)2] (1), the magnetic moment value is lower than the expected spin only value. In all the complexes g(||)>g( perpendicular)>2.0023 and G values within the range 2.5-3.5 are consistent with dx2-y2 ground state. The complexes were given the formula as [(CuL1)2] (1); [Cu(HL1)2] (2); [CuL1bpy] (3); [CuL1phen] (4); [CuL1gamma-pic].2H2O (5); [Cu(HL2)2] (6); [CuL2py].3H2O (7); [CuL2bipy] (8). The structure of the compound 8 have been solved by single crystal X-ray crystallography and was found to be distorted square pyramid around copper(II) ion. PMID- 17720620 TI - Diversity of group A rotavirus strains circulating in Paraguay from 2002 to 2005: detection of an atypical G1 in South America. AB - BACKGROUND: Group A rotaviruses are the main cause of severe gastroenteritis in children worldwide. OBJECTIVES: To survey human rotavirus strains circulating in Paraguay. STUDY DESIGN: One hundred ninety-six rotavirus-positive fecal samples collected from children up to 5 years old, from 2002 to 2005, were characterized. RESULTS: The most common G genotype detected was G9 (36.2%), followed by G1 (34.2%), G2 (11.7%) and G4 (8.7%). Changes in the G genotype frequency were observed from year to year. The G4 genotype was predominant in 2002; G1 in 2003; and G9 from 2004 to 2005. Sequence and phylogenetic analysis of the VP7 gene from Paraguayan G1 strains suggested that the high frequency of G1 in 2003 could be due to the introduction of an atypical sub-lineage. In addition, there were amino acid changes in the variable/antigenic regions of the VP7 gene from G4 and G9 strains detected in different years. CONCLUSIONS: This study further indicates that antigenic pressure can drive the evolution of rotaviruses, and also suggests that a vaccine that protects against the most prevalent strains and its variants, will be necessary to elicit a protective immune response against the range of rotavirus types currently circulating in Paraguay. PMID- 17720621 TI - Anti-HCV IgG avidity index in acute hepatitis C. AB - BACKGROUND: The diagnosis of acute hepatitis C (AHC) is based on seroconversion to positive anti-HCV, which is usually not clinically possible. OBJECTIVE: To determine if avidity of anti-HCV IgG can be used for the diagnosis of AHC infection. STUDY DESIGN: We enrolled 40 consecutive patients with AHC, 16 drug addicts (IVDA) with exacerbation of chronic hepatitis C (IVDA e-CHC group), 21 non-IVDA with exacerbation of chronic hepatitis C (IVDA-free e-CHC group) and 40 with chronic hepatitis C (CHC group). HCV avidity index (HCV-AI) was determined by ELISA on sera pre-diluted 1:10 with 1M guanidine. RESULTS: On admission, HCV AI values were significantly lower in the AHC group (mean+/-S.D.: 0.50+/-0.30) than in IVDA-free e-CHC group (0.97+/-0.08, p<0.0001), IVDA e-CHC group (0.90+/ 0.29, p<0.0001) or CHC group (1.06+/-0.20, p<0.0001). An HCV-AI lower than 0.7 obtained within the 8th day of illness distinguished patients with AHC infection from the IVDA-free e-CHC cases. An increase in HCV-AI was observed in 24 (72.7%) of 33 in AHC group, in none of 13 in IVDA-free e-CHC group and in 3 (27.3%) of 11 in IVDA e-CHC group. CONCLUSION: HCV-AI is useful in identifying AHC infection in patients observed within the 8th day from the onset of symptoms. PMID- 17720622 TI - Real-time PCR assay for the detection and quantification of Legionella pneumophila in environmental water samples: utility for daily practice. AB - We developed a quantitative real-time PCR assay targeting the mip gene of Legionella pneumophila for a prospective study from September 2004 to April 2005. It was compared with a standard culture method (French guideline AFNOR T90-431), analysing 120 water samples collected to monitor the risk related to Legionellae at Nantes hospital and to investigate a case of legionellosis acquired from hospital environment. Samples from six distinct water distribution systems were analysed by DNA extraction, amplification and detection with specific primers and FRET probes. The detection limit was 100 genomic units of L. pneumophila per liter (GU/l), the positivity threshold about 600 GU/l and the quantification limit 800 GU/l. PCR results were divided into three groups: negative (n=63), positive but non-quantifiable (n=22) or positive (n=35). PCR showed higher sensitivity than culture, whereas four culture-positive samples appeared negative by PCR (PCR inhibitor detected for two of them). Although no correlation was observed between both methods and real-time PCR cannot substitute for the reference method, it represents an interesting complement. Its sensitivity, reproducibility and rapidity appear particularly interesting in epidemic contexts in order to identify the source of contamination or to evaluate critical points of contamination in water distribution systems. PMID- 17720623 TI - Physiological limits to exercise performance in the heat. AB - Exercise in the heat results in major alterations in cardiovascular, thermoregulatory, metabolic and neuromuscular function. Hyperthermia appears to be the key determinant of exercise performance in the heat. Thus, strategies that attenuate the rise in core temperature contribute to enhanced exercise performance. These include heat acclimatization, pre-exercise cooling and fluid ingestion which have all been shown to result in reduced physiological and psychophysical strain during exercise in the heat and improved performance. PMID- 17720624 TI - A comparison of fitness and skill among playing positions in sub-elite rugby league players. AB - In rugby league, individual playing positions require a wide range of physical performance qualities and offensive and defensive skills. This study investigated the physical performance, anthropometric, and skill characteristics of specific playing positions in sub-elite rugby league players. Ninety-eight sub-elite rugby league players (mean+/-S.D. age, 22.5+/-4.9 years) participated in this study. Players underwent measurements of anthropometry (height, body mass, and sum of four skinfolds), muscular power (vertical jump), speed (10m, 20m, and 40m sprint), change of direction speed (L run), and maximal aerobic power (multistage fitness test). In addition, two expert coaches independently assessed the skill of players using standardised technical criteria. Hit-up forwards were heavier and had greater skinfold thickness than the adjustables and outside backs positional groups. Furthermore, hit-up forwards had significantly (p<0.05) slower change of direction speed than outside backs, and slower 20m and 40m speed than both the adjustables and outside backs positional groups. Hit-up forwards had a significantly greater (p<0.05) ability to 'hit and spin' than both adjustables and outside backs. The evasion skills (i.e. ability to beat a player and 2 versus 1 ability) of adjustables and outside backs were significantly greater (p<0.05) than hit-up forwards. Adjustables had significantly greater (p<0.05) skills under physiological game stress than hit-up forwards and better catching, ball carrying, and basic passing skills than the hit-up forwards and outside backs. These findings demonstrate that the physical performance, anthropometric, and skill qualities of sub-elite rugby league players vary according to playing position. PMID- 17720625 TI - Recombinant BCG Tokyo (Ag85A) protects cynomolgus monkeys (Macaca fascicularis) infected with H37Rv Mycobacterium tuberculosis. AB - One tuberculosis vaccine candidate that has shown a promising degree of protective efficacy in guinea pigs is recombinant BCG Tokyo (Ag85A)(rBCG Ag85A[Tokyo]). As a next step, cynomolgus monkeys were utilized because they are susceptible to Mycobacterium tuberculosis and develop a continuous course of infection that resembles that in humans both clinically and pathologically. The recombinant BCG vaccine was administered once intradermally in the back skin to three groups of cynomolgus monkeys, and its protective efficacy was compared for 4 months with that of its parental BCG Tokyo strain. Vaccination of the monkeys with the rBCG-Ag85A[Tokyo] resulted in a reduction of tubercle bacilli CFU (p<0.01) and lung pathology in animals challenged intratracheally with 3000 CFU H37Rv M. tuberculosis. Vaccination prevented an increase in the old tuberculin test after challenge with M. tuberculosis and reaction of M. tuberculosis-derived antigen. Thus, it was shown in monkeys that rBCG-Ag85A[Tokyo] induced higher protective efficacy than BCG Tokyo. This warrants further clinical evaluation. PMID- 17720626 TI - Successful treatment with intravenous immunoglobulins in a patient affected by dermatomyositis/systemic lupus erythematosus overlap syndrome and tuberculosis. AB - The case of a 56-year-old woman, with a previous history of systemic lupus erythematosus (SLE), later diagnosed as also affected by active dermatomyositis (DM) associated with tuberculosis (TB) is reported. Since TB is a contra indication to receive immunosuppressive therapy for DM/SLE, intravenous immunoglobulins (IVIG) with low-dose steroids and anti-TB therapy were administered with excellent clinical results. This report underlines the crucial role of IVIG in the treatment of critical patients suffering from connective tissue disorders associated with severe infections. PMID- 17720628 TI - Nondrug treatments for psychogenic nonepileptic seizures: what's the evidence? AB - OBJECTIVE: The purpose of this Cochrane Review was to establish the evidence base for treatment of psychogenic nonepileptic seizures. METHODS: Six hundred eight references were identified using a search strategy designed with the support of the Cochrane Review Epilepsy Group library. The search employed Medline and PsychInfo, and included hand searches of relevant journals (Seizure, Epilepsia, Epilepsy &Behavior, Epilepsy Research). RESULTS: Three studies were found that met the inclusion criteria; two used hypnosis and one used paradoxical therapy. None included detailed reports of improved seizure frequency or quality of life, although reduction in seizure frequency was mentioned. All three studies concluded that the intervention used was beneficial in the treatment of psychogenic nonepileptic seizures. CONCLUSIONS: The limited number of studies and poor methodology preclude these results from being generalizable. There is a need for well-designed clinical trials to identify the most suitable treatments for this population. PMID- 17720627 TI - Single nucleotide polymorphism and haplotype association of the interleukin-8 gene with nasopharyngeal carcinoma. AB - The cytokine interleukin-8 (IL-8) may play a role in the pathogenesis of nasopharyngeal carcinoma (NPC) through the modulation of tumor immune response or enhanced angiogenesis. Polymorphism of IL-8 gene, which may affect the production level of cytokine, has been inversely associated with a number of cancers. To test this hypothesis, we investigated the relationship of IL-8 gene polymorphisms and NPC in a Chinese population. We analyzed single nucleotide polymorphisms (SNPs) of IL-8 gene -845 T/C, -738 T/A, -353 A/T, -251 A/T and +678 T/C in 280 patients with NPC and 290 age and sex matched controls, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polymerase chain reaction-sequence specific primers method (PCR-SSP). There were significant differences in the genotype and allele distribution of -251 A/T polymorphism of the IL-8 gene among cases and controls. The -251 AA and AT genotypes were associated with a significantly increased risk of NPC as compared with the -251 TT genotypes (OR=1.820, 95% CI, 1.120-2.959, P=0.015 and OR=1.590, 95% CI, 1.104 2.290, P=0.013, respectively). Haplotype analysis revealed that the homozygosity of the AAT haplotype (defined by SNPs at positions -353, -251 and +678) of IL-8 gene conveys the highest risk for NPC compared with the homozygosity for the TTC haplotype (OR=1.396; 95% CI, 1.064-1.831; P=0.016). The -251 A/T polymorphism of IL-8 and its haplotype are associated with NPC in a Chinese population. Our data suggests that IL-8 gene may play a role in the development of NPC. PMID- 17720629 TI - Can external and subjective information ever be used to reduce the size of randomised controlled trials? AB - In the design of randomised trials in rare cancers, a Bayesian approach has been advocated, which allows for external and subjective information to be formally incorporated. We explore whether this can be extended more generally to allow for smaller trials to be conducted using a case study involving a trial of nasopharyngeal carcinoma. The external information available at various points during the trial is first summarised in the form of 'prior distributions'. Each of these is then combined with the accumulated data from the trial at that point in time to form 'posterior distributions', from which conclusions are drawn. We have argued that such a framework for the design, analysis and interpretation of a randomised trial in the light of external evidence is particularly useful in situations such as trials in rare cancers. But more generally, it may potentially also allow for smaller trials to be conducted. Although, at this point in time, we are hesitant to recommend the full implementation of the Bayesian methodology to modify the (conventionally) planned trial size we submit that a formal synthesis of the external evidence bearing on the question of concern is a valuable exercise in itself. PMID- 17720630 TI - RecBC enzyme overproduction affects UV and gamma radiation survival of Deinococcus radiodurans. AB - Deinococcus radiodurans recovering from the effect of acute dose of gamma (gamma) radiation shows a biphasic mechanism of DNA double strands breaks repair that involves an efficient homologous recombination. However, it shows higher sensitivity to near-UV (NUV) than Escherichia coli and lacks RecBC, a DNA strand break (DSB) repair enzyme in some bacteria. Recombinant Deinococcus expressing the recBC genes of E. coli showed nearly three-fold improvements in near-UV tolerance and nearly 2 log cycle reductions in wild type gamma radiation resistance. RecBC over expression effect on radiation response of D. radiodurans was independent of indigenous RecD. Loss of gamma radiation tolerance was attributed to the enhanced rate of in vivo degradation of radiation damaged DNA and delayed kinetics of DSB repair during post-irradiation recovery. RecBC expressing cells of Deinococcus showed wild type response to Far-UV. These results suggest that the overproduction of RecBC competes with the indigenous mechanism of gamma radiation damaged DNA repair while it supports near-UV tolerance in D. radiodurans. PMID- 17720631 TI - Dual role of NER in mutagenesis in Pseudomonas putida. AB - Nucleotide excision repair (NER) is one of the most important repair systems which counteracts different forms of DNA damage either induced by various chemicals or irradiation. At the same time, less is known about the functions of NER in repair of DNA that is not exposed to exogenous DNA-damaging agents. We have investigated the role of NER in mutagenesis in Pseudomonas putida. The genome of this organism contains two uvrA genes, uvrA and uvrA2. Genetic studies on the effects of uvrA, uvrA2, uvrB and UvrC in mutagenic processes revealed that all of these genes are responsible for the repair of UV-induced DNA damage in P. putida. However, uvrA plays more important role in this process than uvrA2 since the deletion of uvrA2 gene had an effect on the UV-tolerance of bacteria only in the case when uvrA was also inactivated. Interestingly, the lack of functional uvrB, uvrC or uvrA2 gene reduced the frequency of stationary-phase mutations. The contribution of uvrA2, uvrB and uvrC to the mutagenesis appeared to be most significant in the case of 1-bp deletions whose emergence is dependent on error prone DNA polymerase Pol IV. These data imply that NER has a dual role in mutagenesis in P. putida-besides functioning in repair of damaged DNA, NER is also important in generation of mutations. We hypothesize that NER enzymes may initiate gratuitous DNA repair and the following DNA repair synthesis might be mutagenic. PMID- 17720632 TI - Identification of amygdalin and its major metabolites in rat urine by LC-MS/MS. AB - Amygdalin and its metabolites in rat urine were identified using liquid chromatography-electrospray ionization (ESI) tandem ion-trap mass spectrometry. The purified rat urine sample was separated using a reversed-phase C18 column with 10 mM sodium phosphate buffer (pH 3.1) containing 30% methanol as the mobile phase, amygdalin and its metabolites were detected by on-line mass detector in selected ion monitoring (SIM) mode. The identification of the metabolites and elucidation of their structure were performed by comparing the changes in molecular masses (DeltaM), retention times and MS(2) spectral patterns of metabolites with those of parent drug. At least seven metabolites and the parent drug were found in rat urine after i.v. injection of 100 mg/kg doses of amygdalin. Among them, six metabolites were reported for the first time. PMID- 17720634 TI - Perianal Crohn's disease: classification and clinical evaluation. AB - Perianal manifestations are common in patients with Crohn's disease and include skin tags and haemorrhoids, fissures, ulcers, abscesses, fistulas, stenosis or cancer. Primary lesions include Crohn's fissures and cavitating perianal ulcers. Secondary lesions include deep abscesses, fistulas and strictures. A good classification and anatomical description of these conditions is crucial before embarking on any kind of (medical or surgical) therapy, as this greatly influences management. This review analyses and discusses current classifications of any perianal form of Crohn's disease. PMID- 17720633 TI - The interplay of processivity, substrate inhibition and a secondary substrate binding site of an insect exo-beta-1,3-glucanase. AB - Abracris flavolineata midgut contains a processive exo-beta-glucanase (ALAM) with lytic activity against Saccharomyces cerevisiae, which was purified (yield, 18%; enrichment, 37 fold; specific activity, 1.89 U/mg). ALAM hydrolyses fungal cells or callose from the diet. ALAM (45 kDa; pI 5.5; pH optimum 6) major products with 0.6 mM laminarin as substrate are beta-glucose (61%) and laminaribiose (39%). Kinetic data obtained with laminaridextrins and methylumbelliferyl glucoside suggest that ALAM has an active site with at least six subsites. The best fitting of kinetic data to theoretical curves is obtained using a model where one laminarin molecule binds first to a high-affinity accessory site, causing active site exposure, followed by the transference of the substrate to the active site. The two-binding-site model is supported by results from chemical modifications of amino acid residues and by ALAM action in MUbetaGlu plus laminarin. Low laminarin concentrations increase the modification of His, Tyr and Asp or Glu residues and MUbetaGlu hydrolysis, whereas high concentrations abolish modification and inhibit MUbetaGlu hydrolysis. Our data indicate that processivity results from consecutive transferences of substrate between accessory and active site and that substrate inhibition arises when both sites are occupied by substrate molecules abolishing processivity. PMID- 17720635 TI - The natural history of perianal Crohn's disease. AB - Perianal lesions are exceedingly common in Crohn's disease and many patients have more than one type of lesion. Skin tags, fissures and haemorrhoids may persist over time and are usually managed expectantly or with topical therapy. Perianal and rectovaginal fistulas and associated abscesses often require both local and systemic therapy, and recurrence is common. In general, the clinical course of Crohn's disease is more aggressive in patients with perianal involvement. Established risk factors for perianal disease include colonic disease and young age at disease onset. Classification schema now recognize perianal fistulas as distinct from other forms of penetrating Crohn's disease. Genetic susceptibility factors for perianal disease may exist, but they remain incompletely delineated at present. There is hope that immunosuppressive and biotechnology medications will influence the natural history of perianal disease by preventing invasive surgeries, disease complications and recurrence, but this needs to be confirmed. Cancer, a rare complication of perianal disease, must be suspected when lesions persist despite therapy. PMID- 17720636 TI - Coeliac disease epidemiology is alive and kicking, especially in the developing world. PMID- 17720638 TI - Is gliadin harmful from the first morsel? PMID- 17720637 TI - Hepatic steatosis in chronic hepatitis B develops due to host metabolic factors: a comparative approach with genotype 1 chronic hepatitis C. AB - BACKGROUND/AIMS: Hepatic steatosis has not been adequately studied in chronic hepatitis B, while it is considered to be a cardinal feature in chronic hepatitis C and to be mainly metabolically induced in patients infected with genotype 1. We investigated the prevalence of and the parameters associated with steatosis in HBeAg-negative chronic hepatitis B. METHODS: We studied 213 patients with HBeAg negative chronic hepatitis B and compared them with 163 patients with genotype-1 chronic hepatitis C. Steatosis was semi-quantitatively graded. RESULTS: Steatosis was significantly less frequent in chronic hepatitis B than chronic hepatitis C (60% versus 72%, P=0.016), but there was no difference in the prevalence of moderate/severe steatosis. In chronic hepatitis B, steatosis was associated only with higher body mass index (P=0.002), while moderate/severe steatosis was associated only with higher body mass index (P=0.043) and diabetes (P=0.031). Steatosis was relatively less frequent in chronic hepatitis B than chronic hepatitis C non-diabetic, normal-weight patients (45.6% versus 62.5%, P=0.063), but it did not differ in diabetic and/or overweight/obese patients with chronic hepatitis B or chronic hepatitis C. CONCLUSIONS: Hepatic steatosis in HBeAg negative chronic hepatitis B (a) is less frequent than in genotype-1 chronic hepatitis C, (b) is mainly associated with presence of host metabolic factors, such as high body mass index and diabetes and (c) does not seem to be associated with the severity of liver histological lesions. PMID- 17720639 TI - The colon - the latest terrain for capsule endoscopy. AB - Colonoscopy is the gold standard for evaluating pathologies of the large bowel, including screening for colorectal cancer. The technological features of current colonoscopes have not progressed much in recent years except for improved image and video display. The technique requires intubation and insufflation of the colon which are operator-dependent and involve a learning curve. Colonoscopy is an invasive procedure whose overall risk of complications is approximately 0.3%, increasing to 2% when polypectomy is performed. The PillCam Colon capsule endoscope (Given Imaging Ltd., Yoqneam, Israel) was developed for use as a safe, minimally invasive, non-sedation requiring, patient-friendly modality to visualize the colon. Only the interpretation of findings requires expertise. PillCam capsule endoscopy could be an alternative approach to colonoscopy for screening large populations. We report the first clinical investigations of the safety, feasibility and performance of colon capsule endoscopy compared with standard colonoscopy. PMID- 17720640 TI - Imaging of perianal Crohn's disease. AB - Perianal fistulas and abscesses are common complications of Crohn's disease, affecting up to 50% of patients during their disease course. Accurate diagnosis and classification of perianal disease is crucial before and during treatment to plan an adequate approach for each patient and to avoid irreversible functional consequences. Although examination under anaesthesia has been considered the gold standard for diagnosis and classification of Crohn's disease perianal fistulas, taken alone it does not have perfect accuracy, stressing the need for concomitant or alternative, non-invasive, methods of evaluation. In this context, imaging modalities assessed for diagnosis, classification and monitoring of Crohn's disease perianal fistulas include pelvic magnetic resonance imaging, anorectal endoscopic ultrasonography, transcutaneous perianal ultrasound, fistulography and computed tomography. In particular, magnetic resonance imaging and endoscopic ultrasonography findings have shown the best accuracy, and the ability to influence therapeutic management of these patients. For transcutaneous perianal ultrasound too, good preliminary data have been reported. This paper reviews the available data on imaging methods for the management of perianal Crohn's disease. PMID- 17720641 TI - Enhanced antibactericidal function of W4+-doped titania-coated nickel ferrite composite nanoparticles: a biomaterial system. AB - The study demonstrates a distinct enhancement of antimicrobial activity of W4+ doped titania that is coated on nickel ferrite nanoparticles in comparison to undoped titania. The composite nanoparticles were synthesized by uniquely combining reverse micelle and chemical hydrolysis synthesis methods [Rana S, Rawat J, Misra RDK, Acta Biomater 2005;1:691]. The superior antimicrobial activity of W4+-doped titania is related to the inhibition of electron-hole recombination and decrease in the band gap energy of titania. The function of the ferrite is to facilitate the removal of nanoparticles from the sprayed surface using a small magnetic field. The coating of ferrite nanoparticles with titania retains superparamagnetic character and magnetic strength of composite nanoparticles signifying non-deterioration of magnetic properties and promoting their use as removable antimicrobial photocatalyst nanoparticles. PMID- 17720642 TI - Role of subcutaneous drains in obese patients undergoing elective cholecystectomy: a cohort study. AB - BACKGROUND: Prophylactic drainage of wounds is aimed to reduce the wound complications and thereby morbidity. Obese patients are at more risk. The objective of the present study was to determine whether subcutaneous drainage can reduce such complications in elective abdominal surgery (cholecystectomy) in obese patients. DESIGN: Randomized, prospective and comparative study. METHODS: Two hundred and fifty obese patients with body mass index (BMI) >32 and subcutaneous fat thickness of >3 cm undergoing elective Cholecystectomy were allocated into two groups, viz. study (n=125) and control (n=125). Incision technique was standardized for all the patients. Patients with sepsis, spillage and comorbid conditions were excluded from the study. RESULTS: Overall seroma formation occurred in 11 (8.80%) patients in the study group and 42 (33.60%) patients in the control group (p<0.05), the likelihood of seroma formation without drains was 6.5 times and 9.3 times more in patients with subcutaneous fat thickness of 3-3.9 cm and 4-5 cm, respectively. 71.43% of patients in the control group and 54.55% patients in the study group who developed seroma presented in the first week of surgery. CONCLUSION: Prophylactic use of subcutaneous drains in obese patients undergoing cholecystectomy was found to reduce the seroma formation significantly. PMID- 17720643 TI - Microbiology and management of soft tissue and muscle infections. AB - This review summarizes the microbiological aspects and management of soft tissue and muscle infections. The infections presented are: impetigo, folliculitis, furunculosis and carbuncles, cellulitis, erysipelas, infectious gangrene (includes necrotizing fasciitis or streptococcal gangrene, gas gangrene or clostridium myonecrosis, anaerobic cellulites, progressive bacterial synergistic gangrene, synergistic necrotizing cellulitis or perineal phlegmon, gangrenous balanitis, and gangrenous cellulitis in the immunocompromised patient), secondary bacterial infections complication skin lesions, diabetic and other chronic superficial skin ulcers and subcutaneous abscesses and myositis. These infections often occur in body sites or in those that have been compromised or injured by foreign body, trauma, ischemia, malignancy or surgery. In addition to Group A streptococci and Staphylococcus aureus, the indigenous aerobic and anaerobic cutaneous and mucous membranes local microflora usually is responsible for polymicrobial infections. These infections may occasionally lead to serious potentially life-threatening local and systemic complications. The infections can progress rapidly and early recognition and proper medical and surgical management is the cornerstone of therapy. PMID- 17720644 TI - Comparison of outcomes and donor-site morbidity in unilateral free TRAM versus DIEP flap breast reconstruction. AB - BACKGROUND: At long-term follow up we cannot easily differentiate between patients who have undergone free transverse rectus abdominis musculocutaneous (TRAM) flap and deep inferior epigastric artery perforator (DIEP) flap breast reconstruction in terms of subjective functional limitations of daily activities. The aim of this study was to evaluate postoperative outcomes and long-term subjective functional deficit in patients following unilateral free TRAM compared with DIEP flap breast reconstruction. METHODS: Sixty consecutive patients who underwent unilateral autologous breast reconstruction were included in the study, 30 of whom had undergone a DIEP flap, and 30 a free TRAM flap. Surgical and postoperative outcome data were collected and a postal questionnaire was sent to each patient at least 6 months postoperatively consisting of a short functional assessment questionnaire and a Short Form 36 (SF-36) survey. RESULTS: We found no significant difference in postoperative outcomes or in the subjective ability to perform activities of daily living, including work, domestic activities, sports and hobbies, between patients who underwent TRAM flap breast reconstruction and those who underwent a DIEP flap, and no significant difference between the groups for scores on the physical functioning, role-physical, or bodily pain scales of the SF-36. CONCLUSION: We conclude that harvesting of the free TRAM flap results in no significant difference in postoperative outcomes or in the subjective ability to perform activities of daily living compared with the DIEP flap. PMID- 17720645 TI - Tertiary resurfacing after one of the first free flaps in Europe, a reflection on 30 years of microsurgical progress. AB - Free flaps have been used for over 30 years. During this period, improved anatomical understanding has increased donor options and available pedicle lengths, permitting safer, single-stage reconstructions with simpler anastomoses. Refinements, such as perforator flaps in particular, have greatly improved donor morbidity, recipient site cosmesis, and the ability to replace 'like with like' while retaining options for innervation. This case highlights the evolution from one of Europe's first free tissue transfers, effectively a perforator flap, through the advent of free muscle flaps to the current generation of contourable perforator flaps. Free flap transfer has become increasingly sophisticated, safer, and more predictable, yet the potential quality of reconstructive outcome has changed little. PMID- 17720646 TI - Untreated growth hormone deficiency with extremely short stature, bone dysplasia, cleft lip--palate and severe mental retardation in a 26-year-old man with a de novo unbalanced translocation t(1;12)(q24;q24). AB - We report on a 26-year-old patient presenting with extremely short stature (height 72cm, weight 6.5kg, OFC 42.5cm), facial dysmorphism, cleft lip--palate, severe mental retardation and de novo 1q24.2--q25.2 and 12q24.31 interstitial deletion. He was the only child of non-consanguineous parents and his birth length was 43cm. He had severe feeding difficulties and required enteral nutrition until the age of 3 years. Standard cytogenetic analysis showed an apparently balanced de novo translocation t(1;12)(q24;q24). Endocrine studies at 11 years of age for severe growth retardation revealed multiple pituitary hormone deficiency with severe growth hormone deficiency, but the child was untreated because of associated mental retardation. At 26 years of age, he could not walk or speak and had no signs of puberty. Investigations revealed spondylo-epi metaphyseal dysplasia with severe osteoporosis, enlarged aorta when compared to the patient's size and apparently normal pituitary development. High resolution karyotype showed a 1q24-q25 deletion, and comparative genomic hybridization studies confirmed the 1q interstitial deletion. FISH studies of both breakpoints using PACs and BACs enabled us to further characterize the 1q interstitial deletion (1q24.2-1q25.2) and also revealed a 12q24.31 interstitial microdeletion. This case is compared with previously reported patients with similar deletions, but the untreated pituitary deficiency could also be responsible in part for the severity of the growth deficiency. This observation is of interest for two reasons. First, these deletions could be a clue in the search for a gene responsible for growth hormone deficiency/midline defects. Second, it shows the importance of molecular cytogenetics in the study of de novo apparently balanced translocation with abnormal phenotype. PMID- 17720648 TI - PET-CT in oncology. PMID- 17720647 TI - Two related Dutch families with a clinically variable presentation of cardioskeletal myopathy caused by a novel S13F mutation in the desmin gene. AB - Desmin-related myopathy is characterised by skeletal muscle weakness often combined with cardiac involvement. Mutations in the desmin gene have been described as a cause of desmin-related myopathy (OMIM 601419). We report here on two distantly related Dutch families with autosomal dominant inheritance of desmin-related myopathy affecting 15 family members. A highly heterogeneous clinical picture is apparent, varying from isolated dilated cardiomyopathy to a more generalised skeletal myopathy and mild respiratory problems. Morphological analysis of muscle biopsies revealed intracytoplasmic desmin aggregates (desmin and p62 staining). In both families we identified an identical novel pathogenic heterozygous missense mutation, S13F, in the 'head' domain of the desmin gene which cosegregates with the disease phenotype. This is the 5th reported missense mutation located at the 'head' domain of the desmin gene and the first reported Dutch family with desmin-related myopathy. This article illustrates the importance of analysing the desmin gene in patients with (familial) cardiac conduction disease, dilated cardiomyopathy and/or a progressive skeletal myopathy resembling limb-girdle muscular dystrophy. PMID- 17720649 TI - The story of a fly. PMID- 17720650 TI - Molecular biology of neuroblastoma. AB - Neuroblastoma is one of the most frequently occurring solid tumours in children, especially in the first year of life, when it accounts for 50% of all tumours. It is the second most common cause of death in children, only preceded by accidents. The most peculiar characteristic of neuroblastoma is its clinical heterogeneity. Approximately half of the cases are classified as high risk, with overall survival rates around 40% despite intensive multimodal therapy. Nevertheless, other subsets of neuroblastomas will undergo spontaneous regression and others will show very slow progression. Despite many advances in the past three decades, neuroblastoma has remained an enigmatic challenge to clinical and basic scientists. Elucidation of the exact molecular pathways of neuroblastoma will enable researchers and clinicians to stratify the disease and adapt therapy to the risk of relapse or progression. This review focuses on recent advances in our understanding of the biology of this complex paediatric tumour. Neuroblastoma is already one of the first examples for the use of tumoral genetic markers as a tool for defining tumour behaviour and to aid clinical staging. PMID- 17720652 TI - PET-CT in clinical oncology. AB - Anatomic imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) have been used for many years in clinical oncology. The emergence of positron emission tomography (PET) more than a decade ago was a major breakthrough in the early diagnosis of malignant lesions, as it was based on tumour metabolism and not on anatomy. The merger of both techniques into one thanks to PET-CT cameras has made this technology the most important tool in the management of cancer patients. PET/CT with 18F-FDG is increasingly being used for staging, restaging and treatment monitoring for cancer patients with different types of tumours (lung, breast, colorectal, lymphoma, melanoma, head and neck etc.). At many institutions, PET/CT has replaced separately acquired PET and CT examinations for many oncologic indications. This replacement has occurred despite the fact that only a relatively small number of well designed prospective studies have verified imaging findings against the gold standard of histopathologic tissue evaluation. However, a large number of studies have used acceptable reference standards, such as pathology, imaging and other clinical follow-up findings, for validating PET/CT findings. The impact on the management of patients and the benefits from the information obtained from this anatomo metabolic procedure justify the term "clinical oncology based on PET-CT" as a new concept to be applied in clinical practice. PMID- 17720651 TI - mTOR signalling in human cancer. AB - Inhibitors of mTOR, the mammalian target of rapamycin, have been extensively studied in clinical trials for cancer treatment. Results have been promising, mostly in certain lymphomas, but in solid tumours the results have been generally less encouraging. However, recent results, particularly in renal cell carcinoma, have provided renewed interest in the role of mTOR inhibitors in solid tumours. A rational, and potentially more successful, development of these agents (i.e., RAD001, temsirolimus and AP23573) likely relies in a deeper knowledge of mTOR signalling in cancer, both at the preclinical and clinical levels. These would allow a better selection of patients more likely to respond to the use of biologically active doses of the agents and the development of mechanistically based combinations with other agents. The goal of this review is to provide an update on the complex signalling of mTOR in cancer and on the biological effects of mTOR inhibitors in cancer cells. PMID- 17720653 TI - Toxicity associated to radiotherapy treatment in lung cancer patients. AB - Radiation therapy in combination with other treatments, such as chemotherapy, increases loco-regional control and survival in patients with lung cancer. Nevertheless, the subsequent toxicity of this treatment occurs in up to 37% of the irradiated patients. Some factors related to the patient, including performance status, pulmonary function tests (FEV1, DCLO), tumour site, as well as treatment-related factors such as radiation dose, fractionation and addition of chemotherapy, can be related to the risk of pulmonary toxicity. With the advent of tridimensional conformal radiotherapy (3DCRT), dose-volume histograms can be generated to assess the dose received by the organs at risk. Volume dose (Vdose), mean lung dose (MLD) and normal tissue complication probability (NTCP) are the dosimetric parameters most frequently used. The possible relationship between these parameters and clinical and anatomical factors has to be considered. Steroid treatment should be started soon in case of pneumonitis to avoid the development of late pulmonary fibrosis. Finally, some pharmacological agents to prevent radiation-related pneumonitis are under investigation. PMID- 17720654 TI - Axillary surgery in breast cancer patients. AB - Surgeons have routinely removed ipsilateral axillary lymph nodes from women with breast cancer for over 100 years. The procedure provides important staging information, enhances regional control of the malignancy and may improve survival. As screening of breast cancer has increased, the mean size of newly diagnosed primary invasive breast cancers has steadily decreased and so has the number of women with lymph node metastases. Recognising that the therapeutic benefit of removing normal nodes may be low, alternatives to the routine level I/II axillary lymph node dissection have been sought. A decade ago sentinel lymph node biopsy (SLNB) was introduced. Because of its high accuracy and relatively low morbidity, this technique is now widely used to identify women with histologically involved nodes prior to the formal axillary node dissection. Specifically, SLNB has allowed surgeons to avoid a formal axillary lymph node biopsy in women with histologically uninvolved sentinel nodes, while identifying women with involved sentinel nodes who derive the most benefit from a completion axillary node dissection. Despite the increasing use of SLNB for initial management of the axilla in women with breast cancer, important questions remain regarding patient selection criteria and optimal surgical methods for performing the biopsy. This article discusses the evolution of axillary node surgery for women with breast cancer. PMID- 17720655 TI - Trans-platinum(II) complexes with cyclohexylamine as expectator ligand induce necrosis in tumour cells by inhibiting DNA synthesis and RNA transcription. AB - BACKGROUND: Enhanced removal of cisplatin-DNA adducts has been reported as one of main causes of cell resistance to cisplatin. This particular resistance mechanism may be circumvented by platinum complexes that bind differently to DNA. One line of work is focussed on trans platinum complexes, some of which exhibit antitumour activity similar to or even higher than that of their cis counterparts. METHODS: We synthesised new trans platinum complexes, trans [PtCl2(cyclohexylamine)(dimethylamine)] and trans [PtCl2(OH)2(cyclohexylamine)(dimethylamine)], previously evaluated as cytotoxic agents towards different cancer and normal cell lines. These trans platinum compounds were highly effective against a panel of tumoral cell lines either sensitive to or with acquired resistance to cisplatin. RESULTS: In the present work we examined the mechanisms induced by these compounds to cause tumour cells toxicity. We have found that these compounds induced a complete blockade at the S phase of the cell cycle inhibiting total mRNA transcription and precluding p53 activation. CONCLUSION: In contrast to other DNA-damaging agents, these compounds do not induce senescence-associated permanent arrest. Furthermore, only a small percentage of these cells enter into apoptosis, with most of the population dying by a necrosis-like mechanism. PMID- 17720657 TI - Pathological femur fracture secondary to radiation therapy for soft tissue sarcoma. AB - Bone fracture is a well known possible late complication of radiation treatment. Little has been written about fractures of long bones after irradiation. We present a case of femur bone necrosis secondary to postoperative radiation for a soft tissue sarcoma of the thigh 20 years earlier. Fixation of the diaphyseal fracture and radiological evolution are described. PMID- 17720656 TI - Analysis of fiducial markers used for on-line verification in the external-beam radiotherapy of patients with cranial tumours. AB - PURPOSE: Evaluate the fiducial marker-based position verification in the external beam radiotherapy of patients with cranial tumour. METHODS: Thirteen patients with intracranial tumours were treated with external- beam radiotherapy using 3 gold markers implanted in the skull. Before each fraction the patient was positioned on the treatment table and 2 orthogonal portal images were performed to localise the 3 gold seeds and the target position was calculated using a commercialised computer program (ISOLOC software, MEDTEC). This program provides the couch movements required to move the target to the isocentre. RESULTS: When the set-up error was corrected using the coordinates of the 3 markers, the final movements were less than 2 mm in all cases: lateral, mean v., 1.21 mm; longitudinal, 1.23 mm; and anteroposterior, 1.18 mm. No serious complications related to the gold marker insertion were noted. CONCLUSION: The use of 3 implanted fiducial seeds is an optimal technique for precise set-up in patients with brain tumours treated with external radiotherapy. This commercial system is highly suitable for fractionated stereotactic irradiation. PMID- 17720658 TI - Heart metastases and superior vena cava syndrome. AB - Superior vena cava syndrome (SVCS) may be due to a tumour infiltrating the right atrium. We present two patients with SVCS. The first one was secondary to solitary atrial metastases of rectal adenocarcinoma and benefited from palliative chemotherapy. The second patient had a disseminated large cell B-cell lymphoma with rapid clinical complete response, but she eventually died after relapse. PMID- 17720659 TI - High-dose lopinavir/ritonavir in highly treatment-experienced HIV-1 patients: efficacy, safety, and predictors of response. AB - OBJECTIVE: To investigate the efficacy and safety of high-dose lopinavir/ritonavir (LPV/r) therapy in multiple protease inhibitor, non nucleoside reverse transcriptase inhibitor (NNRTI)-experienced subjects. METHOD: Thirty-six HIV-1-infected subjects were randomized to LPV/r 400/300 mg or 667/167 mg bid in a 48-week, open-label study. Subjects also received investigator selected nucleoside reverse transcriptase inhibitors (NRTIs). Primary outcomes were the proportion of subjects with HIV-1 RNA levels <50 copies/mL at week 24 and time until loss of virologic response through week 48. RESULTS: Six of 17 (35%) and 10 of 19 (53%) subjects in the 400/300 and 667/167 groups, respectively, completed 48 weeks of treatment. Median durations of follow-up in discontinued subjects and all subjects were 15 weeks and 32 weeks, respectively. Forty-four percent of subjects achieved HIV-1 RNA <50 copies/mL at least once; 18% (400/300 mg) and 21% (667/167 mg) of subjects achieved HIV-1 RNA <50 copies/mL at week 24 (intent-to-treat analysis). Corresponding results at week 48 were 18% (400/300 mg) and 26% (667/167 mg). No statistically significant differences in adverse event incidence occurred between treatment groups, except for a higher vomiting rate in the 400/300 mg dose group. Predictors of response included baseline LPV inhibitory quotient and number of active NRTIs. CONCLUSION: Higher doses of LPV/r may provide substantial antiviral activity in multiple class-experienced subjects. PMID- 17720661 TI - Safety, tolerability, and efficacy of darunavir (TMC114) with low-dose ritonavir in treatment-experienced, hepatitis B or C co-infected patients in POWER 1 and 3. AB - PURPOSE: This subanalysis examines the safety and efficacy of darunavir with low dose ritonavir (DRV/r) in hepatitis B or C virus (HBV or HCV) co-infected patients in POWER 1 and 3 trials. METHOD: POWER 1 and 3 enrolled treatment experienced, HIV-infected patients with > or =1 primary protease inhibitor (PI) mutation and HIV-1 RNA >1,000 copies/mL. All patients received an optimized background regimen plus either control PI (almost all ritonavir boosted) or one of four DRV/r doses (POWER 1) or DRV/r 600/100 mg bid (POWER 3). Patients with active HBV or HCV co-infection who did not require treatment for hepatitis were included. Safety parameters were evaluated. RESULTS: Of 634 DRV/r and 63 control (97% ritonavir boosted) patients assessed, 13% and 16%, respectively, had active co-infection. In both groups, more patients with active co-infection than without co-infection had liver-related adverse events (AEs). These AEs were mainly asymptomatic liver transaminase elevations, although changes were slightly less in the DRV/r group (DRV/r, 13% vs. 8%; control PI, 20% vs. 12%). Only two patients (one per treatment arm) discontinued therapy due to grade 3 or 4 alanine and aspartate transaminase elevations. CONCLUSION: DRV/r was generally well tolerated in treatment-experienced, HBV or HCV co-infected patients. No differences in liver-related AEs were observed between treatment groups. PMID- 17720660 TI - Antiretroviral treatment regimen outcomes among HIV-infected prisoners. AB - BACKGROUND: Despite the high prevalence of HIV in correctional settings, the duration of therapy and response to various highly active antiretroviral therapy (HAART) regimens in this setting is unknown. METHOD: Using a retrospective cohort study (1997-2002) of HIV-infected prisoners in Connecticut that linked demographic, pharmacy, and laboratory data, we compared HIV-1 RNA (VL) and CD4 lymphocyte responses to four treatment strategies at baseline and at the end of incarceration. RESULTS: Using an analysis of 1,044 incarceration periods or 1,099 subjects for whom 6 months of continuous data were available, HAART regimens that included a triple NRTI, two NRTIs + either a PI or NNRTI, or a three-class (NRTI+NNRTI+PI) strategy demonstrated no difference in virological and immunological outcomes. The proportion of subjects who were initiated with NRTI, NNRTI, PI, or three-class regimens were 14%, 32%, 46%, and 8%, respectively. For all study groups, the mean change from baseline in CD4 and VL was +74 cells/muL and -0.93 log(10) copies/mL (p < .0001), respectively. Overall, 59% of subjects had an HIV-1 RNA level below the level of detection (<400 copies/mL) by the end of their incarceration. Using Kaplan-Meier curves to examine the time to change in the initial HAART strategy over the incarceration period, the three-class strategy was significantly more likely to be changed earlier than all others (p < .05). CONCLUSION: Although the three-class strategy was less durable, initiating HAART with any strategy resulted in similar and impressive virological and immunological outcomes by the end of incarceration, further supporting prison as an important site for the initiation and provision of effective antiretroviral therapy. PMID- 17720662 TI - Comparative efficacy of nucleoside/nucleotide reverse transcriptase inhibitors in combination with efavirenz: results of a systematic overview. AB - BACKGROUND: Many trials of antiretroviral therapy in treatment-naive subjects have investigated the relative efficacy of the third drug in a treatment regimen. However, the nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) components may also affect efficacy. METHOD: A systematic overview of clinical trials studying initial treatment in naive subjects receiving efavirenz containing regimens and providing week 48 time to loss of virologic response (TLOVR) results was undertaken to compare results with different NRTI combinations. RESULTS: Seven trials studying 3,807 subjects were identified that met the inclusion criteria. Baseline characteristics were similar across studies. Using the week 48 TLOVR results as the primary method of comparison, combinations of tenofovir and lamivudine or emtricitabine appeared to provide improved virologic responses. Similar results were obtained when the proportions of subjects with plasma HIV RNA levels <50 copies/mL were examined. PMID- 17720663 TI - Changes in facial fat in HIV-related lipoatrophy, wasting, and weight gain measured by magnetic resonance imaging. AB - BACKGROUND: Changes in facial fat occurring over time in patients with HIV related lipoatrophy have not been properly quantified. We aimed to define the longitudinal changes in facial fat compartments in patients with lipoatrophy and to compare these with changes accompanying wasting or weight gain. METHOD: Facial MRI scans were performed at baseline and repeated after a median of 10 months in 24 patients, of whom 12 had moderate to severe lipodystrophy continuing antiretroviral therapy, 5 lost weight, and 7 gained weight (more than 10% weight change). RESULTS: Superficial facial fat decreased by a median of 5.2 mL (p = .03) in patients with lipoatrophy, and 8 of 12 individuals showed more than 15% decrease (all of whom were taking stavudine). The decrease was mainly cheek fat. Superficial facial fat decreased by 6.0 mL in patients with weight loss (p = .04) and increased by 20.2 mL (p = .02) in patients with weight gain, and changes occurred in cheek fat, temporal fat, and masseter muscle and temporalis muscle compartments. CONCLUSION: MRI can detect substantial ongoing changes in facial fat in patients with facial lipoatrophy. A characteristic pattern of compartmental change distinguishes lipoatrophy from wasting and weight recovery. MRI should be considered for use in clinical trials of interventions to prevent or treat lipoatrophy and may be useful for documenting changes in individual patients during clinical follow-up. PMID- 17720664 TI - Cost-effectiveness analysis of enfuvirtide (ENF) added to an optimized therapy compared with an optimized therapy in patients with HIV/AIDS. AB - BACKGROUND: Fuzeon (enfuvirtide) (ENF) is the first drug among the HIV fusion inhibitors that has shown high efficacy in HIV-1/AIDS patients resistant to conventional antiretroviral agents. PURPOSE: To analyze the cost-effectiveness of ENF plus optimized therapy (OT) in HIV patients. METHOD: A Markov model was used to calculate the cost-effectiveness of ENF in terms of incremental cost per life year gained. The model has a 10-year horizon, with monthly cycles, and the perspective is the Spanish National Health System. Efficacy rates and transition probabilities were obtained from clinical and epidemiological trials. Resource use data were retrieved from published literature and a panel of clinicians. Unit costs refer to the year 2003. MAIN OUTCOME MEASURE: Incremental cost effectiveness ratio. RESULTS: Adding ENF to OT increased patient life expectancy by 1.6 years (6.2 years with OT compared with 7.8 years with ENF + OT). Total costs were 160,728 euro for OT and 200,859 euro with ENF + OT, mainly due to increasing life expectancy raising resource use and costs. Incremental cost per life-year gained with ENF was 25,082 euro. CONCLUSION: ENF plus OT increased life expectancy for HIV-1-treated patients and is an efficient treatment option. PMID- 17720665 TI - Human immunodeficiency virus (HIV) and malaria interaction in sub-Saharan Africa: the collision of two Titans. AB - HIV and malaria are among the leading causes of morbidity and mortality in sub Saharan Africa, home to 10% of the world's population. An association between HIV and malaria is expected in theory, however, there is conflicting evidence regarding the impact of HIV infection on parasite loads. HIV-associated immunosuppression contributes to more frequent and more severe malaria and reduced efficacy of antimalarials in pregnant women and adults. These effects are modified by the endemicity and stability of malaria transmission. Co-infection with malaria and HIV in pregnant women is associated with anemia, low birth weight, and increased risk of infant mortality to a greater extent than infection with either disease alone. Studies investigating the impact of placental malaria on mother-to-child HIV-1 transmission continue to show conflicting results. This article attempts to review the pertinent information available about the interaction between HIV and malaria and information about chemoprophylaxis and treatment issues. Although much has been published in the last 10 years regarding the interaction of HIV and malaria in sub-Saharan Africa, we still need more information so as to understand the issues that will help us develop effective programs. PMID- 17720666 TI - Comparison of lopinavir level between the two formulations (soft-gel capsule and tablet) in HIV-infected pregnant women. PMID- 17720667 TI - Durable suppression possible with FOTO treatment schedule in subjects on nevirapine-based regimens. PMID- 17720669 TI - The role of conservation agriculture in sustainable agriculture. AB - The paper focuses on conservation agriculture (CA), defined as minimal soil disturbance (no-till, NT) and permanent soil cover (mulch) combined with rotations, as a more sustainable cultivation system for the future. Cultivation and tillage play an important role in agriculture. The benefits of tillage in agriculture are explored before introducing conservation tillage (CT), a practice that was borne out of the American dust bowl of the 1930s. The paper then describes the benefits of CA, a suggested improvement on CT, where NT, mulch and rotations significantly improve soil properties and other biotic factors. The paper concludes that CA is a more sustainable and environmentally friendly management system for cultivating crops. Case studies from the rice-wheat areas of the Indo-Gangetic Plains of South Asia and the irrigated maize-wheat systems of Northwest Mexico are used to describe how CA practices have been used in these two environments to raise production sustainably and profitably. Benefits in terms of greenhouse gas emissions and their effect on global warming are also discussed. The paper concludes that agriculture in the next decade will have to sustainably produce more food from less land through more efficient use of natural resources and with minimal impact on the environment in order to meet growing population demands. Promoting and adopting CA management systems can help meet this goal. PMID- 17720670 TI - [Experience with only preoperative radiotherapy of non-metastatic rectal tumours]. AB - INTRODUCTION: It is an accepted fact that the local recurrence rate can be decreased up to 50% for the metastatic rectum tumours irradiated only preoperatively. MATERIALS AND METHODS: 181 patients having rectum tumour were irradiated preoperatively with 36 or 40 Gy between 1990 and 2001. The classification was made according to the modified Astler-Coller pathological staging system. The radiation treatment was carried out with telecobalt unit or high energy photon of linear accelerator after computerized radiation treatment planning. RESULTS: The most important characterizing factor for the efficiency of the preoperative irradiation is the local recurrence rate that was found to be 21.56% in our investigation. The survival rate was significantly influenced by the age of the patient and the applied dose. CONCLUSION: Our statistical analysis was applied to investigate the efficiency of the only preoperatively irradiated patients. The results are in agreement with the reported contributions. PMID- 17720672 TI - [Our experience with trans-obturator tape surgery in 150 cases]. AB - BACKGROUND: Nearly 30% of adult European women suffers from urinary incontinence. The recently introduced Trans-Obturator Tape (TOT) implant provides a new surgical technique for the treatment of stress incontinence. PATIENTS AND METHODS: Preoperative work-up included detailed history taking, stress-test and Q tip test, general and gynaecological physical examination and completion of the QUID questionnaire. Equivocal cases were further investigated with urodynamic assessment. TOT implantation was performed on 150 patients. Clinical efficacy of the treatment was evaluated with the QUID questionnaire. RESULTS: Mean age of the patients was 50.8 years (SD = 8.64). 69 patients (46%) had genuine stress incontinence, 33 patients (22%) had urge incontinence, 48 patients (32%) had mixed type incontinence with dominant stress component. Mean length of follow-up was 16 months (4-26 months). Preoperative severity score of stress incontinence was 11.78 on average, while that of urge component was 6.63. On average, it took 25 minutes to complete the operation. Four out of the 150 operations were complicated by adverse event. Twelve patients required prolonged catheterisation exceeding 24 hours with a maximum of 5 days. The mean length of hospital stay was 4.76 days (SD = 0.8). Evaluation of postoperative questionnaires resulted in a mean severity score of 2.22 for the stress component and 2.59 for the urge component. In a patient satisfaction survey 46 patients reported the treatment as excellent (47.4%), 39 as good (40.2%), 7 as satisfactory (7.2%), 3 as suboptimal (3.1%) and 2 patients reported the procedure as ineffective (2.1%). CONCLUSIONS: The procedure is an effective, quick, minimally invasive method of treating urinary incontinence. The operation requires short hospital stay and carries a low morbidity. PMID- 17720671 TI - [Prevalence of childhood asthma in Baranya County, Hungary, between 2003 and 2006]. AB - INTRODUCTION: The prevalence of bronchial asthma, allergic rhinitis and atopic dermatitis (AD) in children has constantly and significantly increased worldwide in the past decades. Recent publications, however, reported a moderate decrease or levelling off in this parameter. The authors estimated the prevalence of bronchial asthma and asthmatic complaints among schoolchildren in Baranya county in the years 2003 and 2006 in order to register the possible changes. MATERIALS AND METHODS: Both surveys were carried out by means of identical questionnaires which were consistent with the ISAAC Phase III. protocol. The data were collected in 16 primary schools (6 in a city, 10 in small settlements and villages) in February 2006. Finally 2404 questionnaires (1124 boys, 1280 girls) in two age groups, among 6-7 and 13-14-year-old children were processed and compared to the data derived from the survey done in 2003. RESULTS: The prevalence of the "wheezing-ever" and "physician diagnosed asthma" did not change during the observation period (2006: 20.2% and 6.7%; 2003: 19.8% and 8.2%) but there was a significant increase in the frequency of "wheezing in the last 12 months" (2006: 9.6%; 2003: 6.8%). As expected, significantly higher prevalence rates were detected among boys and in the 6-7-year-old age group than among girls and in the 13-14-year-old age group in both surveys. There was no significant difference in the two surveys in the prevalence of bronchial asthma and asthmatic signs between children from a city and from small settlements. CONCLUSION: During the observation period of three years there was a significant increase "wheezing in the last 12 months", but the prevalence of "wheezing-ever" as well as the "physician-diagnosed asthma" remained unchanged. PMID- 17720673 TI - [Influence of psychiatric and psychosomatic disorders on quality of life]. AB - INTRODUCTION AND AIMS: The term 'quality of life' has received a growing highlight in relation to the care of chronically ill people during the past decades. The main goal of the present study has been to analyze patients' quality of life regarding the following diagnoses: headache (tension headache); mood disorders (depression); anxiety, and comorbid states, involving some psychological variables, such as hostility or social support. METHODS: There were 157 patients participating in the study who came from a registered patients' pool in the Neuropsychiatric Rehabilitation Ward, Department of Psychiatry, University of Szeged, during the spring semester of 2005. The final sample size contained 151 patients who might be sorted into five main disease groups: mood disorders (depression); anxiety disorders; mixed psychiatric diagnosis; headache; and comorbid diagnosis (headache and psychiatric disorder together). The mean scores of the scales of patients' quality of life were investigated according to gender and disease groups; in addition, we also analyzed the psychological background of the quality of life. RESULTS: Based on factor analysis, two factors of the quality of life scale were detected: one factor labelled 'everyday activities' factor (including items such as work, financial situation, nutrition, sexual life or self-actualization), and another one labelled 'social activities' factor (e.g., activities with spouse, family, other persons, religious and community activities). According to the disease groups, differences could be detected particularly in the field of everyday activities; especially patients suffering from mood disorders reported higher levels of deterioration of their quality of life, whereas in comparison with them, patients of headache showed less changes. When there was comorbid psychiatric illness besides headache, a more determinant deterioration of the quality of life could be detected. Hostility and psychosomatic/anxiety symptoms contributed mostly to deterioration of the quality of life in the field of everyday activities, moreover, with growing age, the patients experienced a greater level of deterioration of their quality of life. Among the disease groups, the presence of mood disorder lowered mostly the patients' quality of life. In case of the quality of life factor 'social activities', social support was a protective factor. CONCLUSIONS: In this study, we would like to draw the attention to the influences of psychosomatic and psychiatric disorders on patients' quality of life since with this help we may get closer to a deeper understanding of patient behavior. The quality of life study identifies not only the non-beneficial effects but also maps the positive ones. This implies the possibility of effective adaptation. PMID- 17720674 TI - [Development of silent gastric carcinoid in a type 1 diabetic patient with primer hypothyreosis]. AB - Type 1 diabetes is usually associated with other autoimmune diseases. Parietal cell antibodies (PCA) are found in 20% of type 1 diabetic patients which might be an early sign of autoimmune gastritis and pernicious anemia. PCA destroy the gastric H+/K+ ATP-ase. The chronic auto-destruction of the proton pump leads to hypo/achlorhydria and hypergastrinemia which leads to the hyper/dysplasia of enterochromaffin-like cells (ECL). ECL hyper/dysplasia is known to increase the likelihood of gastric carcinoid tumor development in affected patients. Gastric carcinoid tumors forming from the hyperplasia of ECL cells are found in 4-9% of patients having autoimmune gastritis or pernicious anemia. The 29-years-old type 1 diabetic patient, having primer hyperthyroidism was admitted to our clinic because of gastric pain. Results of endoscopy and biopsy showed multiple small polyps in the fundus with non-antral hypergastrinemic (type A) atrophic gastritis. The parietal cell antibody test was positive, the serum chromogranin A level was 289,7 ng/ml (normal value $ 98 ng/ml), TSH level was 9,93 mIU/L. The histological examination indicated carcinoid tumor. Sandostatin therapy was started then partial gastrectomy was done. After the operation the plasma chromogranin level normalized. Non-antral, multiple polyps could cover silent neuroendocrine tumors, which are slowly growing benign endocrine tumors, however, they also might be high malignity endocrine carcinomas. These tumors could be easily recognized in the clinical practice by measuring the serum or tissue chromogranin A level and other markers of tumor growth. Thus screening of gastric endocrine tumors in type 1 diabetic patients with co-morbid autoimmune diseases is recommended. PMID- 17720675 TI - [Grasping reflex activity in utero is one element of fetal behavior (Grasping activity is a part of fetal ethology)]. AB - It is well known the newborns and infants activity include touching and grasping of various surrounding things lasting some months in postnatal period. The study involved observation of fetal grasping reflex during last trimester of pregnancy. The author was able to observe 6 episodes of grasping the umbilical cord in an other fetus grasping his scrotum, and another of his penis. When checked with Doppler sonography flow velocity waveforms of umbilical artery were disturbed temporarily. All fetuses were born some days or weeks later in good condition. Grasping reflex is an innocuous transitory episode from prenatal to postnatal life, without adverse sequelae. It is only one aspect of fetal behavior, and proof of its hereditary nature. PMID- 17720679 TI - On the balance between niche and neutral processes as drivers of community structure along a successional gradient: insights from alpine and sub-alpine meadow communities. AB - BACKGROUND AND AIMS: Neutral theory predicts that the diversity and relative abundance of species in ecological communities do not depend on their specific traits. This prediction remains controversial, as many studies suggest that variations in the niches of species determine the structure of communities. The aim of this study was to test empirically the relative importance of niche and neutral processes as drivers of species abundance within plant communities along a successional gradient. METHODS: Information on the abundance (density and frequency) and traits (aboveground individual biomass and seed mass) of > 90 species was collected in alpine and sub-alpine meadows of the Tibet Plateau (China). A successional gradient (1, 3, 15 and 30 years after abandonment) was established in a sub-alpine meadow. The relationships between species traits and their abundance were evaluated using regression models. KEY RESULTS: Seed mass was negatively related to both species density (r = -0.6270, P < 0.001) and frequency (r = -0.5335, P = 0.005) in the 1-year meadow. Such relationships disappeared along the successional gradient evaluated (P > 0.07 in the 3-, 15- and 30-year meadows). Data gathered in all sites showed a significant negative relationship between the average individual biomass of a given species and its density within the community (r < -0.30, P < 0.025 in all cases). CONCLUSIONS: The results show that seed mass was a key driver of species abundance in early successional communities, and that niche forces may become more important as succession progresses. They also indicate that predictions from neutral theory, in its current form, do not hold for the meadow communities studied. PMID- 17720680 TI - Sympodial construction of Fibonacci-type leaf rosettes in Pinguicula moranensis (Lentibulariaceae). AB - BACKGROUND AND AIMS: The leaf rosettes of the carnivorous Pinguicula moranensis follow a spiral phyllotaxis approaching a Fibonacci pattern while the stalked flowers arise from extra-axillary sites between the leaves. The organization of this rosette has been discussed by various authors, with various results. The aim of the present study was to clarify the development of the flowering rosettes of this species. METHODS: The formation of the rosettes is shown with the aid of scanning electron microscopy. KEY RESULTS AND CONCLUSIONS: The scanning electron micrographs show that each flower terminates an article (sympodial unit). The leaves of consecutive articles of such sympodially constructed rosettes are arranged along a spiral Fibonacci pattern (with divergence angles around 137 degrees). This results from homodromy of leaf initiation in consecutive articles with the first leaf (prophyll) of a new article inserted in an obliquely transverse position next to the floral scape that terminates the former article. Sympodial construction of flowering shoots and leaf rosettes is also known from Aloe, Gunnera and Philodendron. As a by-product of this study, the unidirectional development of the Pinguicula flower is confirmed and discussed. PMID- 17720681 TI - Oxygen concentrations inside the traps of the carnivorous plants Utricularia and Genlisea (Lentibulariaceae). AB - BACKGROUND AND AIMS: Species of Utricularia and Genlisea (Lentibulariaceae) are carnivorous, capturing small prey in traps which are physiologically very active, with abundant quadrifid and bifid glands. Traps of Utricularia have walls composed of two cell layers, and are filled with water. Diverse communities of commensal microorganisms often live inside the traps. Genlisea forms long, hollow subterranean traps of foliar origin, growing in anoxic wet substrate. Knowledge of the O(2) concentrations inside Utricularia and Genlisea traps is vital for understanding their physiological functioning and conditions for the life of commensals. To test the hypothesis that prey are killed by anoxia inside the traps, and to measure respiration of traps, [O(2)] was measured in the fluid in mature traps of these species. METHODS: Oxygen concentration and electrical redox potential were measured using a small Clark-type oxygen sensor and a miniature platinum electrode, respectively, in the fluid of excised and intact traps of six aquatic Utricularia species and in Genlisea hispidula traps. KEY RESULTS: Steady state [O(2)] in the traps of both genera always approached zero (median 0.0-4.7 microm). The [O(2)] decreased after electrodes were inserted into Utricularia traps at a rate which ranged from 0.09 to 1.23 mm h(-1) and was lower in traps of irradiated and intact shoots with higher [O(2)] in shoot tissues. Redox potential ranged from -24 to -105 mV in the traps, confirming the very small or zero [O(2)]. CONCLUSIONS: Very small or zero [O(2)], effectively anoxia, is demonstrated in Utricularia and Genlisea traps. This is probably below the critical [O(2)] for prey survival, and causes captured prey to die of suffocation. Internal trap glands and trap commensals are considered to be adapted to facultative anoxia interrupted by limited periods of higher [O(2)] after firings. PMID- 17720682 TI - Childhood social and economic well-being and health in older age. AB - Childhood socioeconomic status (SES) acts over a lifetime to influence adult health outcomes. Whether the impact of childhood SES differs by age or race/ethnicity is unclear. The authors studied 20,566 community-living US adults aged > or =50 years. Parental education was the main predictor. Outcomes evaluated (1998-2002) included self-reported health and functional limitation. The influence of childhood SES on later-life health was also examined in groups stratified by age and race/ethnicity, with adjustment for demographic factors and current SES. Participants' mean age was 67 years; 57% were women. By race/ethnicity, 76% were White, 14% were Black, and 8% were Latino. The relation between low parental education and fair/poor self-rated health declined with advancing age (age 50-64 years: adjusted odds ratio (AOR) = 1.42, 95% confidence interval (CI): 1.24, 1.63; age > or =80 years: AOR = 1.14, 95% CI: 0.96, 1.36). The relation between low parental education and fair/poor self-rated health differed across racial/ethnic groups and was significant in White (AOR = 1.33, 95% CI: 1.21, 1.47) and Black (AOR = 1.37, 95% CI: 1.14, 1.64) participants but not Latinos. These findings suggest that childhood SES affects health status through midlife but the effects may abate in late life; its effects also may be weaker in Latinos than in Whites or Blacks. PMID- 17720683 TI - Malathion exposure and the incidence of cancer in the agricultural health study. AB - Malathion is the most common organophosphate insecticide applied in the United States, and while some studies suggest that it may be clastogenic, its carcinogenicity has not been demonstrated in rodents. However, malathion has been associated with non-Hodgkin's lymphoma in several epidemiologic studies. The authors investigated associations between malathion exposure and cancer among 19,717 pesticide applicators enrolled in the Agricultural Health Study between 1993 and 1997. Information on lifetime years and days per year of use and intensity of malathion exposure was obtained with self-administered questionnaires prior to the onset of any cancer. The average follow-up time was 7.5 years (1993-2002). Rate ratios and 95% confidence intervals were calculated using Poisson regression, adjusting for potential confounders. Overall, lifetime days of malathion use (top tertile of exposure, >39 days) was not associated with all cancers combined (rate ratio = 0.97, 95% confidence interval: 0.81, 1.15). The risk of non-Hodgkin's lymphoma was not associated with malathion use, although the number of cases was small. The risk of melanoma with more than 39 lifetime exposure-days was 0.39 (95% confidence interval: 0.14, 1.03). In summary, malathion exposure was not clearly associated with cancer at any of the sites examined. Although the rate ratios for melanoma were reduced, small numbers and lack of experimental evidence suggest that the observed reductions may have arisen by chance. PMID- 17720685 TI - Shared neural resources between music and language indicate semantic processing of musical tension-resolution patterns. AB - Harmonic tension-resolution patterns have long been hypothesized to be meaningful to listeners familiar with Western music. Even though it has been shown that specifically chosen musical pieces can prime meaningful concepts, the empirical evidence in favor of such a highly specific semantic pathway has been lacking. Here we show that 2 event-related potentials in response to harmonic expectancy violations, the early right anterior negativity (ERAN) and the N500, could be systematically modulated by simultaneously presented language material containing either a syntactic or a semantic violation. Whereas the ERAN was reduced only when presented concurrently with a syntactic language violation and not with a semantic language violation, this pattern was reversed for the N500. This is the first piece of evidence showing that tension- resolution patterns represent a route to meaning in music. PMID- 17720684 TI - Lack of orientation and direction selectivity in a subgroup of fast-spiking inhibitory interneurons: cellular and synaptic mechanisms and comparison with other electrophysiological cell types. AB - Neurons in cat area 17 can be grouped in 4 different electrophysiological cell classes (regular spiking, intrinsically bursting, chattering, and fast spiking [FS]). However, little is known of the functional properties of these different cell classes. Here we compared orientation and direction selectivity between these cell classes in cat area 17 and found that a subset of FS inhibitory neurons, usually with complex receptive fields, exhibited little selectivity in comparison with other cell types. Differences in occurrence and amplitude of gamma-range membrane fluctuations, as well as in numbers of action potentials in response to optimal visual stimuli, did not parallel differences observed for orientation and direction selectivity. Instead, differences in selectivity resulted mostly from differences in tuning of the membrane potential responses, although variations in spike threshold also contributed: weakly selective FS neurons exhibited both a lower spike threshold and more broadly tuned membrane potential responses in comparison with the other cell classes. Our results are consistent with the hypothesis that a subgroup of FS neurons receives connections and possesses intrinsic properties allowing the generation of weakly selective responses. The existence of weakly selective inhibitory neurons is consistent with orientation selectivity models that rely on broadly tuned inhibition. PMID- 17720686 TI - Cortical connections of the macaque anterior intraparietal (AIP) area. AB - We traced the cortical connections of the anterior intraparietal (AIP) area, which is known to play a crucial role in visuomotor transformations for grasping. AIP displayed major connections with 1) areas of the inferior parietal lobule convexity, the rostral part of the lateral intraparietal area and the SII region; 2) ventral visual stream areas of the lower bank of the superior temporal sulcus and the middle temporal gyrus; and 3) the premotor area F5 and prefrontal areas 46 and 12. Additional connections were observed with the caudal intraparietal area and the ventral part of the frontal eye field. This study suggests that visuomotor transformations for object-oriented actions, processed in AIP, rely not only on dorsal visual stream information related to the object's physical properties but also on ventral visual stream information related to object identity. The identification of direct anatomical connections with the inferotemporal cortex suggests that AIP also has a unique role in linking the parietofrontal network of areas involved in sensorimotor transformations for grasping with areas involved in object recognition. Thus, AIP could represent a crucial node in a cortical circuit in which hand-related sensory and motor signals gain access to representations of object identity for tactile object recognition. PMID- 17720687 TI - A frontoparietal network for spatial attention reorienting in the auditory domain: a human fMRI/MEG study of functional and temporal dynamics. AB - Several studies have identified a supramodal network critical to the reorienting of attention toward stimuli at novel locations and which involves the right temporoparietal junction and the inferior frontal areas. The present functional magnetic resonance imaging (fMRI)?magnetoencephalography (MEG) study investigates: 1) the cerebral circuit underlying attentional reorienting to spatially varying sound locations; 2) the circuit related to the regular change of sound location in the same hemifield, the change of sound location across hemifields, or sounds presented randomly at different locations on the azimuth plane; 3) functional temporal dynamics of the observed cortical areas exploiting the complementary characteristics of the fMRI and MEG paradigms. fMRI results suggest 3 distinct roles: the supratemporal plane appears modulated by variations of sound location; the inferior parietal lobule is modulated by the cross meridian effect; and the inferior frontal cortex is engaged by the inhibition of a motor response. MEG data help to elucidate the temporal dynamics of this network by providing high-resolution time series with which to measure latency of neural activation manipulated by the reorienting of attention. PMID- 17720688 TI - Auxin fluxes in the root apex co-regulate gravitropism and lateral root initiation. AB - Root architecture plays an important role in water and nutrient acquisition and in the ability of the plant to adapt to the soil. Lateral root development is the main determinant of the shape of the root system and is controlled by external factors such as nutrient concentration. Here it is shown that lateral root initiation and root gravitropism, two processes that are regulated by auxin, are co-regulated in Arabidopsis. A mathematical model was generated that can predict the effects of gravistimulations on lateral root initiation density and suggests that lateral root initiation is controlled by an inhibitory fields mechanism. Moreover, gene transactivation experiments suggest a mechanism involving a single auxin transport route for both responses. Finally, co-regulation may offer a selective advantage by optimizing soil exploration as supported by a simple quantitative analysis. PMID- 17720689 TI - Distinct modulations of the hexokinase1-mediated glucose response and hexokinase1 independent processes by HYS1/CPR5 in Arabidopsis. AB - The Arabidopsis mutant hypersenescence 1 (hys1), that is allelic to constitutive expresser of pathogenesis-related genes 5 (cpr5), displays phenotypes related to glucose signalling and defence responses. In the present study, it is shown that the hys1 mutation boosts the inhibitory effects of glucose upon the greening of seedlings and reduces the antagonistic activities of ethylene and cytokinin toward this inhibition. Neither the glucose content nor the sensitivities to ethylene, cytokinin, and abscisic acid were found to differ between wild-type and hys1 seedlings. However, disruption of the gene encoding hexokinase1 (HXK1), which acts as a glucose sensor, partially suppressed the glucose hypersensitive phenotype of the hys1 mutant. These results thus suggest that the hys1 mutation promotes a process associated with the HXK1-mediated glucose response during greening. By contrast, additional hys1 phenotypes, including an increase in salicylic acid (SA), production of abnormal trichomes, and early senescence, were not suppressed by the loss of HXK1. Surprisingly, the hxk1 and hys1 mutations acted synergistically towards an increased SA accumulation. Hence, HYS1/CPR5 appears to be a versatile protein that modulates both the HXK1-mediated glucose response and various HXK1-indepndent processes that are involved in growth control. A possible role for HYS1/CPR5 as a component of the networks that regulate growth control is discussed. PMID- 17720690 TI - The problem of rooting rapid radiations. AB - There are many examples of groups (such as birds, bees, mammals, multicellular animals, and flowering plants) that have undergone a rapid radiation. In such cases, where there is a combination of short internal and long external branches, correctly estimating and rooting phylogenetic trees is known to be a difficult problem. In this simulation study, we tested the performances of different phylogenetic methods at estimating a tree that models a rapid radiation. We found that maximum likelihood, corrected and uncorrected neighbor-joining, and corrected and uncorrected parsimony, all suffer from biases toward specific tree topologies. In addition, we found that using a single-taxon outgroup to root a tree frequently disrupts an otherwise correct ingroup phylogeny. Moreover, for uncorrected parsimony, we found cases where several individual trees (in which the outgroup was placed incorrectly) were selected more frequently than the correct tree. Even for parameter settings where the correct tree was selected most frequently when using extremely long sequences, for sequences of up to 60,000 nucleotides the incorrectly rooted trees were each selected more frequently than the correct tree. For all the cases tested here, tree estimation using a two taxon outgroup was more accurate than when using a single-taxon outgroup. However, the ingroup was most accurately recovered when no outgroup was used. PMID- 17720691 TI - Relationship between physician characteristics and their injection use in Korea. AB - OBJECTIVE: To determine the relationships among physicians' knowledge and beliefs, perceived patient demand and treatment with injection drugs in Korean primary care settings. DESIGN: A cross-sectional, nationwide survey. SETTING: A total of 644 clinics were selected from the 9660 clinics with more than 1000 patient visits from April 1 to June 30, 2004, among four specialties (general practice, internal medicine, otorhinolaryngology, family medicine) that dealt mainly with acute upper respiratory infections in primary care settings. PARTICIPANTS: We surveyed one physician per clinic with a questionnaire investigating their knowledge and beliefs on and perceived patient demand for injections. Among the 644 physicians, the data of 608 were analysed after responses with incomplete data were excluded. The survey data were merged with their injection prescription rate for acute upper respiratory infections. Main outcome measure Prescription rate for injection drugs. RESULTS: The mean prescription rate for injection drugs per physician was 41.8%. Of respondents, 85.2% had faulty knowledge and beliefs about injection drugs, and 72.9% perceived a strong patient demand for injections. Older, male and generalist physicians had higher prescription rate. After controlling for physician and clinic characteristics, the prescription rates were significantly related with physicians' knowledge and beliefs on and perception of patient demand for injection drugs. CONCLUSIONS: Physicians with faulty knowledge and beliefs on and a perception of strong patient demand for injection drugs had higher prescription rates. Some potential interventions are described to encourage primary care physicians to use injection drugs appropriately in South Korea. PMID- 17720692 TI - Getting to the 'roots' of patient safety. PMID- 17720693 TI - Lipoproteins and their receptors in embryonic development: more than cholesterol clearance. AB - Previously, the relevance of lipoproteins and their receptors has mainly been discussed in terms of cholesterol clearance in the adult organism. Now, findings from nematodes to fruit flies to mammals all point towards novel and unexpected roles for lipoprotein metabolism in the control of key regulatory pathways in the developing embryo, including signaling through steroid hormones and throughout the hedgehog and Wnt signaling pathways. Here, we discuss the emerging view of how lipoproteins and their receptors regulate embryogenesis. PMID- 17720694 TI - FoxF is essential for FGF-induced migration of heart progenitor cells in the ascidian Ciona intestinalis. AB - Heart development requires precise coordination of morphogenetic movements with progressive cell fate specification and differentiation. In ascidian embryos, FGF/MAPK-mediated activation of the transcription factor Ets1/2 is required for heart tissue specification and cell migration. We found that FoxF is one of the first genes to be activated in heart precursors in response to FGF signaling. We identified the FoxF minimal heart enhancer and used a cis-trans complementation test to show that Ets1/2 can interact with the FoxF enhancer in vivo. Next, we found that FoxF function is required downstream and in parallel to the FGF/MAPK/Ets cascade for cell migration. In addition, we demonstrated that targeted expression of a dominant-negative form of FoxF inhibits cell migration but not heart differentiation, resulting in a striking phenotype: a beating heart at an ectopic location within the body cavity of juveniles. Taken together, our results indicate that FoxF is a direct target of FGF signaling and is predominantly involved in the regulation of heart cell migration. PMID- 17720696 TI - SULF1 and SULF2 regulate heparan sulfate-mediated GDNF signaling for esophageal innervation. AB - Heparan sulfate (HS) plays an essential role in extracellular signaling during development. Biochemical studies have established that HS binding to ligands and receptors is regulated by the fine 6-O-sulfated structure of HS; however, mechanisms that control sulfated HS structure and associated signaling functions in vivo are not known. Extracellular HS 6-O-endosulfatases, SULF1 and SULF2, are candidate enzymatic regulators of HS 6-O-sulfated structure and modulate HS dependent signaling. To investigate Sulf regulation of developmental signaling, we have disrupted Sulf genes in mouse and identified redundant functions of Sulfs in GDNF-dependent neural innervation and enteric glial formation in the esophagus, resulting in esophageal contractile malfunction in Sulf1(-/-);Sulf2(-/ ) mice. SULF1 is expressed in GDNF-expressing esophageal muscle and SULF2 in innervating neurons, establishing their direct functions in esophageal innervation. Biochemical and cell signaling studies show that Sulfs are the major regulators of HS 6-O-desulfation, acting to reduce GDNF binding to HS and to enhance GDNF signaling and neurite sprouting in the embryonic esophagus. The functional specificity of Sulfs in GDNF signaling during esophageal innervation was established by showing that the neurite sprouting is selectively dependent on GDNF, but not on neurotrophins or other signaling ligands. These findings provide the first in vivo evidence that Sulfs are essential developmental regulators of cellular HS 6-O-sulfation for matrix transmission and reception of GDNF signal from muscle to innervating neurons. PMID- 17720695 TI - Vascular remodeling of the mouse yolk sac requires hemodynamic force. AB - The embryonic heart and vessels are dynamic and form and remodel while functional. Much has been learned about the genetic mechanisms underlying the development of the cardiovascular system, but we are just beginning to understand how changes in heart and vessel structure are influenced by hemodynamic forces such as shear stress. Recent work has shown that vessel remodeling in the mouse yolk sac is secondarily effected when cardiac function is reduced or absent. These findings indicate that proper circulation is required for vessel remodeling, but have not defined whether the role of circulation is to provide mechanical cues, to deliver oxygen or to circulate signaling molecules. Here, we used time-lapse confocal microscopy to determine the role of fluid-derived forces in vessel remodeling in the developing murine yolk sac. Novel methods were used to characterize flows in normal embryos and in embryos with impaired contractility (Mlc2a(-/-)). We found abnormal plasma and erythroblast circulation in these embryos, which led us to hypothesize that the entry of erythroblasts into circulation is a key event in triggering vessel remodeling. We tested this by sequestering erythroblasts in the blood islands, thereby lowering the hematocrit and reducing shear stress, and found that vessel remodeling and the expression of eNOS (Nos3) depends on erythroblast flow. Further, we rescued remodeling defects and eNOS expression in low-hematocrit embryos by restoring the viscosity of the blood. These data show that hemodynamic force is necessary and sufficient to induce vessel remodeling in the mammalian yolk sac. PMID- 17720697 TI - Porcupine-mediated lipid-modification regulates the activity and distribution of Wnt proteins in the chick neural tube. AB - A long-term goal of developmental biology is to understand how morphogens establish gradients that promote proper tissue patterning. A number of reports describe the formation of the Wg (Wnt1) gradient in Drosophila and have shown that Porcupine, a predicted membrane-bound O-acyl transferase, is required for the correct distribution of Wg protein. The discovery that Wnts are palmitoylated on a conserved cysteine residue suggests that porcupine activity and Wnt palmitoylation are important for the generation of Wnt gradients. To establish the role of porcupine in Wnt gradient formation in vertebrates, we tested the role of porcupine/Wnt palmitoylation in human embryonic kidney 293T cells and in the chick neural tube. Our results lead us to conclude that: (1) vertebrate Wnt1 and Wnt3a possess at least one additional site for porcupine-mediated lipid modification; (2) porcupine-mediated lipid-modification of Wnt proteins promotes their activity in 293T cells and in the chick neural tube; and (3) porcupine mediated lipid-modification reduces the range of activity of Wnt1 and Wnt3a in the chick neural tube. These findings highlight the importance of porcupine mediated lipid modifications in the formation of vertebrate Wnt activity gradients. PMID- 17720698 TI - Mucin 15 is expressed in human placenta and suppresses invasion of trophoblast like cells in vitro. AB - BACKGROUND: Trophoblast invasion is crucial for the development of normal placentas. Mucins are suggested to be involved in cancer invasion. However, the function of mucins in trophoblast invasion has never been reported. This study was to investigate the expression of mucin (MUC) 15 in human placenta and its role in trophoblast invasion. METHODS: MUC15 mRNA in human tissues was analyzed by Northern blot. MUC15 mRNA and protein in human placenta were detected by real time RT-PCR and Western blot, respectively. The distribution of MUC15 was revealed by immunohistochemistry. The effects of MUC15 on trophoblast invasion in vitro were analyzed by matrigel invasion assay in human choriocarcinoma JAR and JEG-3 cells. RESULTS: MUC15 was expressed most highly in human placenta. MUC15 mRNA and protein increased with gestational age (P < 0.05, first versus third trimester). Immunohistochemistry showed that MUC15 protein was expressed by both cytotrophoblasts and syncytiotrophoblasts, especially at the apical membrane of syncytiotrophoblasts. In addition, MUC15 was found to be present in the glandular epithelium of the decidua. Overexpression of MUC15 substantially decreased matrigel invasion of JAR and JEG-3 cells by 87.5 +/- 1.1 and 83.8 +/- 5.7%, respectively, versus control, which was closely associated with an increase in mRNA expression of tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2. Knockdown of MUC15 with small interfering RNA significantly reversed these effects (P < 0.05). CONCLUSIONS: Differential expression of MUC15 in human placentas may play a critical role in the regulation of trophoblast invasion. PMID- 17720699 TI - Histone deacetylase inhibitor-induced glycodelin enhances the initial step of implantation. AB - BACKGROUND: The complex molecular pathways governing implantation are unclear and ethical limitations limit studies in humans. Reversible histone acetylation regulates gene transcription and histone deacetylase inhibitors (HDACI) induce specific genes. Suberoylanilide hydroxamic acid (SAHA), a HDACI recently approved as an anti-cancer drug, induces the morphological and functional differentiation of human endometrial gland cells through up-regulation of glycodelin, a secretory phase dominant protein. METHODS: We investigated whether SAHA improves implantation in an in vitro implantation assay using the human endometrial adenocarcinoma cell line, Ishikawa and the choriocarcinoma cell line, JAR. RESULTS: In an in vitro implantation assay, JAR spheroids attached and adhered to Ishikawa cells in a time dependent manner. Glycodelin induction, following treatment with ovarian steroid hormones or SAHA, enhanced implantation. The improvement in implantation was also obtained when glycodelin was overexpressed without stimulation and was almost completely abrogated by glycodelin gene silencing. CONCLUSIONS: This study demonstrates that glycodelin is a key regulatory protein of implantation and suggests that SAHA may have a capacity to supplant steroid derivatives in the treatment of infertility. PMID- 17720700 TI - Thyroid autoimmunity and thyroid dysfunction in women with endometriosis. AB - BACKGROUND: Women with endometriosis may have higher rates of autoimmune disorders, including hypothyroidism. The objective of this study was to compare the prevalence of thyroid dysfunction and autoimmune thyroid disease (AITD) between women with endometriosis and a control group. METHODS: This was a cross sectional study carried out in 148 women with surgically confirmed endometriosis and 158 controls. The mean age of the study group was 34.6 (7.1 SD) years (range 21-42) and 32.1 (7.7 SD) years (range 18-44) for controls. Serum levels of thyroid-stimulating hormone, free thyroxine and the anti-thyroperoxidase and anti thyroglobulin antibodies were evaluated. RESULTS: Thyroid disorders were identified in 20.9% of the endometriosis group and 26.5% of the control group (P = 0.25). The overall frequency of thyroid dysfunction was 12.2% and 10.8% for the endometriosis and control groups, and the frequency of positive thyroid antibodies, 14.9% and 22.2%, respectively (P = 0.20). Endometriosis stage and infertility history were not associated with thyroid dysfunction and AITD in the study group. CONCLUSIONS: The prevalence of thyroid dysfunction and AITD was similar in the two study groups. Screening for thyroid disturbances in women with endometriosis is not indicated. PMID- 17720701 TI - Umbilical cord anomalies are more frequent in twins after assisted reproduction. AB - BACKGROUND: The objective of this study is to analyse differences in cord characteristics between naturally conceived twins and twins born after assisted reproduction. METHODS: Between 1985 and 2004, the East Flanders Prospective Twin Survey (EFPTS) registered 4159 twin pairs. We compared cord characteristics between 2119 naturally conceived dizygotic (DZ) twin members and 2243 DZ twin members originating from assisted reproductive technologies (ART). Data were adjusted for intra-twin correlation, year of birth, maternal age, gestational age, parity, sex of the child and number of placentas. RESULTS: Marginal cord insertion, velamentous cord insertion and single umbilical artery (SUA) occur more frequently in twins following infertility treatment (P < 0.001). The incidence of velamentous cord insertion increases proportionate with 'invasiveness' of reproductive techniques: 3.6% in naturally conceived twins versus 5% in twins after artificial induction of ovulation (AIO) [odds ratio (OR) 1.45; 95% confidence interval (CI) 0.99-2.11], 7.4% in twins after IVF (OR 1.49; 95% CI 1.26-1.77) and 10.4% in twins after ICSI (OR 1.31; 95% CI 1.14-1.51). SUA has the highest incidence in twins after AIO: 1.9% compared with 0.6% in naturally conceived twins (OR 3.19; 95% CI 1.66-6.11). CONCLUSIONS: Umbilical cords of twins born after ART have more pathologic characteristics when compared with cords of naturally conceived twins. PMID- 17720702 TI - Effects of supplemental perioperative oxygen on post-operative abdominal wound adhesions in a mouse laparotomy model with controlled respiratory support. AB - BACKGROUND: Post-operative adhesion formation is a major clinical problem. Tissue oxygenation is one of the most important determinants in adhesion formation. The objective of this study was to investigate whether supplemental perioperative oxygen could reduce post-operative adhesion formation through increasing the peritoneal tissue oxygen tension (PitO(2)) in a mouse model. METHODS: Adult C57BJ6 mice were randomly assigned to two groups: Group 1 (n = 20), Fraction of Inspired Oxygen (FiO(2)): 0.21; Group 2 (n = 20), FiO(2): 0.80. On day 0, over the course of the 90 min procedure including the 60 min of laparotomy, PitO(2) was continuously monitored. On day 7, a second laparotomy was performed to assess abdominal wound adhesions. Real-time RT-PCR was performed to measure expression levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) mRNA in peritoneal tissues. RESULTS: The PitO(2) levels in Group 2 were significantly higher compared to Group 1 (P < 0.001) and controls (P < 0.003). There was no significant difference in the incidence of abdominal wound adhesions; however, the severity of adhesions was significantly reduced in Group 2 compared to Group 1 (P < 0.03). A significantly higher tPA/PAI-1 mRNA ratio was detected in Group 2 and the controls compared to Group 1 (P < 0.02 and P < 0.002, respectively). CONCLUSIONS: Supplemental perioperative oxygen may help to reduce post-operative adhesion formation. PMID- 17720703 TI - LICORN: learning cooperative regulation networks from gene expression data. AB - MOTIVATION: One of the most challenging tasks in the post-genomic era is the reconstruction of transcriptional regulation networks. The goal is to identify, for each gene expressed in a particular cellular context, the regulators affecting its transcription, and the co-ordination of several regulators in specific types of regulation. DNA microarrays can be used to investigate relationships between regulators and their target genes, through simultaneous observations of their RNA levels. RESULTS: We propose a data mining system for inferring transcriptional regulation relationships from RNA expression values. This system is particularly suitable for the detection of cooperative transcriptional regulation. We model regulatory relationships as labelled two layer gene regulatory networks, and describe a method for the efficient learning of these bipartite networks from discretized expression data sets. We also evaluate the statistical significance of such inferred networks and validate our methods on two public yeast expression data sets. AVAILABILITY: http://www.lri.fr/~elati/licorn.html. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 17720704 TI - A review of feature selection techniques in bioinformatics. AB - Feature selection techniques have become an apparent need in many bioinformatics applications. In addition to the large pool of techniques that have already been developed in the machine learning and data mining fields, specific applications in bioinformatics have led to a wealth of newly proposed techniques. In this article, we make the interested reader aware of the possibilities of feature selection, providing a basic taxonomy of feature selection techniques, and discussing their use, variety and potential in a number of both common as well as upcoming bioinformatics applications. PMID- 17720705 TI - Comparative assessment of plasmid and oligonucleotide DNA substrates in measurement of in vitro base excision repair activity. AB - Mammalian base excision repair (BER) is mediated through at least two subpathways designated 'single-nucleotide' (SN) and 'long-patch' (LP) BER (2-nucleotides long/more repair patch). Two forms of DNA substrate are generally used for in vitro BER assays: oligonucleotide- and plasmid-based. For plasmid-based BER assays, the availability of large quantities of substrate DNA with a specific lesion remains the limiting factor. Using sequence-specific endonucleases that cleave only one strand of DNA on a double-stranded DNA substrate, we prepared large quantities of plasmid DNA with a specific lesion. We compared the kinetic features of BER using plasmid and oligonucleotide substrates containing the same lesion and strategic restriction sites around the lesion. The K(m) for plasmid DNA substrate was slightly higher than that for the oligonucleotide substrate, while the V(max) of BER product formation for the plasmid and oligonucleotide substrates was similar. The catalytic efficiency of BER with the oligonucleotide substrate was slightly higher than that with the plasmid substrate. We conclude that there were no significant differences in the catalytic efficiency of in vitro BER measured with plasmid and oligonucleotide substrates. Analysis of the ratio of SN BER to LP BER was addressed using cellular extracts and a novel plasmid substrate. PMID- 17720706 TI - CTnDOT integrase performs ordered homology-dependent and homology-independent strand exchanges. AB - Although the integrase (IntDOT) of the Bacteroides conjugative transposon CTnDOT has been classified as a member of the tyrosine recombinase family, the reaction it catalyzes appears to differ in some features from reactions catalyzed by other tyrosine recombinases. We tested the ability of IntDOT to cleave and ligate activated attDOT substrates in the presence of mismatches. Unlike other tyrosine recombinases, the results revealed that IntDOT is able to perform ligation reactions even when all the bases within the crossover region are mispaired. We also show that there is a strong bias in the order of strand exchanges during integrative recombination. The top strands are exchanged first in reactions that appear to require 2 bp of homology between the partner sites adjacent to the sites of cleavage. The bottom strands are exchanged next in reactions that do not require homology between the partner sites. This mode of coordination of strand exchanges is unique among tyrosine recombinases. PMID- 17720707 TI - Identification of eukaryotic promoter regulatory elements using nonhomologous random recombination. AB - Understanding the regulatory logic of a eukaryotic promoter requires the elucidation of the regulatory elements within that promoter. Current experimental or computational methods to discover regulatory motifs within a promoter can be labor intensive and may miss redundant, unprecedented or weakly activating elements. We have developed an unbiased combinatorial approach to rapidly identify new upstream activating sequences (UASs) in a promoter. This approach couples nonhomologous random recombination with an in vivo screen to efficiently identify UASs and does not rely on preconceived hypotheses about promoter regulation or on similarity to known activating sequences. We validated this method using the unfolded protein response (UPR) in yeast and were able to identify both known and potentially novel UASs involved in the UPR. One of the new UASs discovered using this approach implicates Crz1 as a possible activator of Hac1, a transcription factor involved in the UPR. This method has several advantages over existing methods for UAS discovery including its speed, potential generality, sensitivity and lack of false positives and negatives. PMID- 17720708 TI - Altered target site specificity variants of the I-PpoI His-Cys box homing endonuclease. AB - We used a yeast one-hybrid assay to isolate and characterize variants of the eukaryotic homing endonuclease I-PpoI that were able to bind a mutant, cleavage resistant I-PpoI target or 'homing' site DNA in vivo. Native I-PpoI recognizes and cleaves a semi-palindromic 15-bp target site with high specificity in vivo and in vitro. This target site is present in the 28S or equivalent large subunit rDNA genes of all eukaryotes. I-PpoI variants able to bind mutant target site DNA had from 1 to 8 amino acid substitutions in the DNA-protein interface. Biochemical characterization of these proteins revealed a wide range of site binding affinities and site discrimination. One-third of variants were able to cleave target site DNA, but there was no systematic relationship between site binding affinity and site cleavage. Computational modeling of several variants provided mechanistic insight into how amino acid substitutions that contact, or are adjacent to, specific target site DNA base pairs determine I-PpoI site binding affinity and site discrimination, and may affect cleavage efficiency. PMID- 17720709 TI - Nucleosome and transcription activator antagonism at human beta-globin locus control region DNase I hypersensitive sites. AB - Locus control regions are regulatory elements that activate distant genes and typically consist of several DNase I hypersensitive sites coincident with clusters of transcription activator binding sites. To what extent nucleosomes and activators occupy these sites together or exclusively has not been extensively studied in vivo. We analyzed the chromatin structure of human beta-globin locus control region hypersensitive sites in erythroid cells expressing embryonic and fetal globin genes. Nucleosomes were variably depleted at hypersensitive sites HS1-HS4 and at HS5 which flanks the 5' of the locus. In lieu of nucleosomes, activators were differentially associated with these sites. Erythroid-specific GATA-1 resided at HS1, HS2 and HS4 but the NF-E2 hetero-dimer was limited to HS2 where nucleosomes were most severely depleted. Histones H3 and H4 were hyperacetylated and H3 was di-methylated at K4 across the LCR, however, the H3 K4 MLL methyltransferase component Ash2L and histone acetyltransferases CBP and p300 occupied essentially only HS2 and the NF-E2 motif in HS2 was required for Ash2L recruitment. Our results indicate that each hypersensitive site in the human beta globin LCR has distinct structural features and suggest that HS2 plays a pivotal role in LCR organization at embryonic and fetal stages of globin gene expression. PMID- 17720710 TI - Functional characterization of Rad18 domains for Rad6, ubiquitin, DNA binding and PCNA modification. AB - Rad18 is a ubiquitin E3 ligase that monoubiquitinates PCNA on stalled replications forks. This allows recruitment of damage-tolerant polymerases for damage bypass and DNA repair. In this activity, the Rad18 protein has to interact with Rad6, the E2 ubiquitin-conjugating enzyme, ubiquitin, PCNA and DNA. Here we analyze the biochemical interactions of specific domains of the Rad18 protein. We found that the Rad6/Rad18 complex forms stable dimers in vitro. Consistent with previous findings, both the Ring domain and a C-terminal region contribute to the Rad6 interaction, while the C-terminus is not required for the interaction with PCNA. Surprisingly we find that the C2HC zinc finger is important for interaction with ubiquitin, apparently analogous to the interactions of classical zinc fingers with ubiquitin such as found in the UBZ and UBM domains in Y-family polymerases. Finally we find that the SAP domain, but not the zinc finger domain, is capable of DNA binding in vitro. PMID- 17720711 TI - The yeast Pif1p DNA helicase preferentially unwinds RNA DNA substrates. AB - Pif1p is the prototypical member of the PIF1 family of DNA helicases, a subfamily of SFI helicases conserved from yeast to humans. Baker's yeast Pif1p is involved in the maintenance of mitochondrial, ribosomal and telomeric DNA and may also have a general role in chromosomal replication by affecting Okazaki fragment maturation. Here we investigate the substrate preferences for Pif1p. The enzyme was preferentially active on RNA-DNA hybrids, as seen by faster unwinding rates on RNA-DNA hybrids compared to DNA-DNA hybrids. When using forked substrates, which have been shown previously to stimulate the enzyme, Pif1p demonstrated a preference for RNA-DNA hybrids. This preferential unwinding could not be correlated to preferential binding of Pif1p to the substrates that were the most readily unwound. Although the addition of the single-strand DNA-binding protein replication protein A (RPA) stimulated the helicase reaction on all substrates, it did not diminish the preference of Pif1p for RNA-DNA substrates. Thus, forked RNA-DNA substrates are the favored substrates for Pif1p in vitro. We discuss these findings in terms of the known biological roles of the enzyme. PMID- 17720712 TI - PROCOGNATE: a cognate ligand domain mapping for enzymes. AB - PROCOGNATE is a database of protein cognate ligands for the domains in enzyme structures as described by CATH, SCOP and Pfam, and is available as an interactive website or a flat file. This article gives an overview of the database and its generation and presents a new website front end, as well as recent increased coverage in our dataset via inclusion of Pfam domains. We also describe navigation of the website and its features. The current version (1.3) of PROCOGNATE covers 4123, 4536, 5876 structures and 377, 326, 695 superfamilies/families in CATH, SCOP and Pfam, respectively. PROCOGNATE can be accessed at: http://www.ebi.ac.uk/thornton-srv/databases/procognate/ PMID- 17720713 TI - Sequence occurrence and structural uniqueness of a G-quadruplex in the human c kit promoter. AB - The 22-nt c-kit87 promoter sequence is unique within the human genome. Its fold and tertiary structure have recently been determined by NMR methods [Phan,A.T., Kuryavyi,V., Burge,S., Neidle,S. and Patel,D.J. (2007) Structure of an unprecedented G-quadruplex scaffold in the c-kit promoter. J. Am. Chem. Soc., 129, 4386-4392], and does not have precedent among known DNA quadruplexes. We show here using bioinformatics and molecular dynamics simulations methods that (i) none of the closely related sequences (encompassing all nucleotides not involved in the maintenance of structural integrity) occur immediately upstream (<100 nt) of a transcription start site, and (ii) that all of these sequences correspond to the same stable tertiary structure. It is concluded that the c kit87 tertiary structure may also be formed in a very small number of other loci in the human genome, but the likelihood of these playing a significant role in the expression of particular genes is very low. The c-kit87 quadruplex thus fulfils a fundamental criterion of a 'good' drug target, in that it possesses distinctive three-dimensional structural features that are only present in at most a handful of other genes. PMID- 17720714 TI - Nanoparticle-based detection and quantification of DNA with single nucleotide polymorphism (SNP) discrimination selectivity. AB - Sequence-specific DNA detection is important in various biomedical applications such as gene expression profiling, disease diagnosis and treatment, drug discovery and forensic analysis. Here we report a gold nanoparticle-based method that allows DNA detection and quantification and is capable of single nucleotide polymorphism (SNP) discrimination. The precise quantification of single-stranded DNA is due to the formation of defined nanoparticle-DNA conjugate groupings in the presence of target/linker DNA. Conjugate groupings were characterized and quantified by gel electrophoresis. A linear correlation between the amount of target DNA and conjugate groupings was found. For SNP detection, single base mismatch discrimination was achieved for both the end- and center-base mismatch. The method described here may be useful for the development of a simple and quantitative DNA detection assay. PMID- 17720715 TI - Analysis of the XPA and ssDNA-binding surfaces on the central domain of human ERCC1 reveals evidence for subfunctionalization. AB - Human ERCC1/XPF is a structure-specific endonuclease involved in multiple DNA repair pathways. We present the solution structure of the non-catalytic ERCC1 central domain. Although this domain shows structural homology with the catalytically active XPF nuclease domain, functional investigation reveals a completely distinct function for the ERCC1 central domain by performing interactions with both XPA and single-stranded DNA. These interactions are non competitive and can occur simultaneously through distinct interaction surfaces. Interestingly, the XPA binding by ERCC1 and the catalytic function of XPF are dependent on a structurally homologous region of the two proteins. Although these regions are strictly conserved in each protein family, amino acid composition and surface characteristics are distinct. We discuss the possibility that after XPF gene duplication, the redundant ERCC1 central domain acquired novel functions, thereby increasing the fidelity of eukaryotic DNA repair. PMID- 17720716 TI - Isolation of SIP, a protein that interacts with SPB, a possible transcriptional regulatory factor in Rhodobacter sphaeroides. AB - SPB is a transcriptional factor in Rhodobacter sphaeroides that represses expression of the puf operon under aerobic or semi-aerobic light conditions. Here, we identified a 17,500 Da protein designated SIP (SPB interaction protein) that interacts with SPB, as determined by binding to an SPB-His(x6) fusion protein-Ni column. The SPB-SIP interaction in vivo was confirmed by an immunoprecipitation assay. The level of transcripts and protein of SIP did not differ for all growth conditions tested, indicating that regulation of the SIP SPB interaction, if any, is not through modulation of sip or spb expression but rather by modification of the proteins. PMID- 17720717 TI - Floral development of an asexual and female-like mutant carrying two deletions in gynoecium-suppressing and stamen-promoting functional regions on the Y chromosome of the dioecious plant Silene latifolia. AB - Sexual dimorphism is controlled by genes on the Y chromosome in the dioecious plant Silene latifolia. K034 is the first mutant with female flowers and asexual flowers in one individual. Its stamens are suppressed completely, and its gynoecium exhibits two suppression patterns. One gynoecium resembles a thin rod, as in wild-type males (asexual flower); the other is imperfectly suppressed, having 1-3 carpels (female-like flower). The ratio of these patterns was 9 : 1. To exclude the possibility of chimerism in K034, we crossed a female-like flower of K034 with a wild-type male. Progeny obtained from this crossing had asexual and female-like flowers in one individual. This two-flower-type phenotype was inherited without separating. To examine the identity of flower organs in K034, we analyzed the development of asexual and female-like flowers using scanning electron microscopy and in situ hybridization with SLM1 and SLM2 (orthologs of AGAMOUS and PISTILLATA, respectively) as probes. Mitotic spreads of root tip chromosomes from hairy root cultures showed that K034 had 25 chromosomes. Fluorescent in situ hybridization analysis, using a subtelomeric repetitive sequence (KpnI subfamily) as a probe, indicated that K034 possessed two X chromosomes and one Y chromosome (Y(d)), of which Y(d) had been rearranged to lose the pseudoautosomal region (PAR). PCR analysis using Y-specific sequence tagged site (STS) markers clarified that Y(d) of K034 had two other deletions in gynoecium-suppressing and stamen-promoting regions. It is reasonable to suggest that these sex chromosomal abnormalities resulted in two abnormal sexual phenotypes: the asexual and imperfect female (female-like) flowers in K034. PMID- 17720718 TI - Highly efficient isothermal DNA amplification system using three elements of 5' DNA-RNA-3' chimeric primers, RNaseH and strand-displacing DNA polymerase. AB - We developed an efficient method of isothermally amplifying DNA termed ICAN, Isothermal and Chimeric primer-initiated Amplification of Nucleic acids. This method allows the amplification of target DNA under isothermal conditions at around 55 degrees C using only a pair of 5'-DNA-RNA-3' chimeric primers, a thermostable RNaseH and a DNA polymerase with strong strand-displacing activity. ICAN is capable of amplifying DNA at least several times greater than the amount produced with PCR by increasing primer concentration. This method would be applicable for on-site DNA detection including gene diagnosis, and would also be suitable for 'real time' detection when combined with a cycling probe. PMID- 17720719 TI - Investigation of the molecular mechanism of ICAN, a novel gene amplification method. AB - Isothermal and Chimeric primer-initiated Amplification of Nucleic acids (ICAN) allows the amplification of target DNA under isothermal conditions at around 55 degrees C using only a pair of 5'-DNA-RNA-3' chimeric primers, thermostable RNaseH and a DNA polymerase with strand-displacing activity (H. Mukai et al. J. Biochemistry, in the preceding paper in this issue). Here we elucidated the mechanism of ICAN by analysing the nicking site of RNaseH, behaviour of chimeric primers and extension products. We found that the ICAN reaction was composed of two unique mechanisms, multi-priming and template-switching, that were responsible for the highly efficient amplifying capability of ICAN. The simultaneous occurrence of two types of reactions, one based on multi-priming and the other based on template-switching, is likely to drive the DNA amplification in ICAN. PMID- 17720720 TI - Co-activation of synovial fibroblasts by laminin-111 and transforming growth factor-beta induces expression of matrix metalloproteinases 3 and 10 independently of nuclear factor-kappaB. AB - We showed previously that the attachment of synovial fibroblasts to laminin (LM) 111 in the presence of transforming growth factor-beta induces significant expression of the matrix metalloproteinase (MMP)-3. Here we go on to investigate the regulation of additional MMPs and their specific tissue inhibitors of matrix proteases (TIMPs). Changes in steady-state mRNA levels encoding TIMPs and MMPs were investigated by quantitative reverse transcription-polymerase chain reaction. Production of MMPs was monitored by a multiplexed immunoarray. Signal transduction pathways were studied by immunoblotting. Attachment of synovial fibroblasts to LM-111 in the presence of transforming growth factor-beta induced significant increases in MMP-3 mRNA (12.35-fold, p < 0.001) and protein (mean 62 ng/ml, sixfold, p < 0.008) and in expression of MMP-10 mRNA (11.68-fold, p < 0.05) and protein (54 ng/ml, 20-fold, p > or = 0.02). All other TIMPs and MMPs investigated failed to show this LM-111-facilitated transforming growth factor beta response. No phosphorylation of nuclear factor-kappaB was observed. We conclude that co-stimulation of synovial fibroblasts by LM-111 together with transforming growth factor-beta suffices to induce significant expression of MMP 3 and MMP-10 by synovial fibroblasts and that this induction is independent of nuclear factor-kappaB phosphorylation. PMID- 17720722 TI - Genetic associations in peripheral joint osteoarthritis and spinal degenerative disease: a systematic review. AB - We conducted a systematic review of genetic association studies for osteoarthritis of the peripheral joints (OA) and spinal degenerative disease (SDD). Electronic searches were carried out for any English language article reporting on a gene association study for either OA or SDD published up until the end of 2006. A team of seven reviewers used a standardised template to extract data in duplicate. In all, 90 studies fulfilled our inclusion criteria, reporting a total of 94 significant associations from 83 different genes. We found relatively few instances in which a specific gene-disease association had been analysed by more than one study, and there were 14 cases in which significant associations were replicated in independent studies (at joints associated with the AGC1, ASPN, COL9A2, COL9A3, COL11A2, ESR1, FZRB, HFE, IL1A, IL1RN, PTGS2 and VDR genes). METHOD: logical and reporting problems were widespread, including failure to report full results, missing population details, multiple testing, and over-reliance on subgroup analysis. In summary, the complex phenotypes of OA and SDD may have made it difficult for researchers to focus their efforts. The field is dominated by isolated analyses of disparate potential associations, a problem that is amplified by the frequent analysis of different polymorphisms within individual genes. Flaws in study methodology and interpretation undoubtedly increase the risk of publication bias. Closer adherence to published recommendations (in particular those produced by HuGENet) will help to ensure that future studies are well-designed and build on current understanding, rather than simply adding to the growing bank of potential associations. PMID- 17720721 TI - Systemic lupus erythaematosus in a multiethnic US cohort (LUMINA) LIII: disease expression and outcome in acute onset lupus. AB - OBJECTIVE: To determine the features associated with acute onset systemic lupus erythaematosus (SLE). METHODS: A total of 631 SLE patients from LUMINA (for "lupus in minority populations: nature vs nurture"), a multiethnic (Hispanics, African-Americans and Caucasians) cohort, were studied. Acute disease onset was defined as the accrual of > or = 4 American College of Rheumatology (ACR) criteria for the classification of SLE in < or = 4 weeks. Socioeconomic demographic features, clinical manifestations, disease activity, damage accrual, mortality, autoantibodies, HLA class II and FCGR alleles, behavioural/psychological variables were compared between patients with acute and insidious disease onset by univariable (chi(2) and Student t test) and multivariable (stepwise logistic regression) analyses. RESULTS: A total of 94 (15%) patients had acute disease onset. In the multivariable analysis, patients with acute onset lupus had more renal involvement (odds ratio (OR) = 1.845, 95% CI 1.076-3.162; p = 0.026) and higher disease activity (OR = 1.057, 95% CI 1.005 1.112; p = 0.030). By contrast, age (OR = 0.976, 95% CI 0.956-0.997; p = 0.025), education (OR = 0.901, 95% CI 0.827-0.983, p = 0.019), health insurance (OR = 0.423, 95% CI 0.249-0.718; p = 0.001) and skin involvement (OR = 0.346, 95% CI 0.142-0.843; p = 0.019) were negatively associated with acute onset lupus. No differences were found regarding the serological, genetic and behavioural/psychological features; this was also the case for damage accrual and mortality. CONCLUSIONS: Patients with acute onset lupus seem to be younger, have a lower socio-economic status and display more severe disease in terms of clinical manifestations and disease activity. However, intermediate (damage) and long-term (mortality) outcomes appear not to be influenced by the type of disease onset in SLE. PMID- 17720723 TI - The B cell in systemic lupus erythaematosus: a rational target for more effective therapy. AB - Current treatment options for systemic lupus erythaematosus (SLE) are diverse and poorly defined, and aggressive therapy can be associated with serious toxicity and tolerability issues. There is, therefore, a need for new and improved treatments to be studied thoroughly in well-designed controlled trials. B Cell dysfunction has emerged as a key pathophysiological component of SLE and is a prime target for the development of new agents for a wide range of lupus severity, including advanced disease. Although many current drugs appear to modify B cell function, the advent of new, targeted therapies offers the hope of improved efficacy and a better long-term tolerability profile. PMID- 17720724 TI - Genetic association of interleukin-21 polymorphisms with systemic lupus erythematosus. AB - OBJECTIVE: The aetiology of systemic lupus erythematosus (SLE) is incompletely understood. Both genetic and environmental factors are implicated in the pathogenesis of the disease. Herein, we describe genetic association between SLE and polymorphisms in the interleukin (IL)-21 gene. The reported effect of IL-21 on B-cell differentiation into plasma cells and its effect on dendritic cell maturation and T-cell responses make IL-21 an attractive candidate gene for SLE. METHODS: Three single nucleotide polymorphisms (SNPs) in the IL-21 gene were genotyped in a total of 2636 individuals (1318 cases and 1318 controls matched for age, sex and race). Population-based case-control association analyses were performed. RESULTS: We found a genetic association with SLE and two SNPs located within the IL-21 gene (rs907715: chi(2) = 11.55, p<0.001; rs2221903: chi(2) = 5.49, p = 0.019). Furthermore, genotypes homozygous for the risk alleles were more frequent than genotypes homozygous for the non-risk alleles in European American patients as compared to controls (rs907715 (GG versus AA): odds ratio (OR) = 1.66, p = 0.0049; rs2221903 (GG versus AA): OR = 1.60, p = 0.025). CONCLUSION: Our findings indicate that IL-21 polymorphism is a candidate association with SLE. The functional effects of this association, when revealed, might improve our understanding of the disease and provide new therapeutic targets. PMID- 17720725 TI - Infliximab inhibits bone resorption by circulating osteoclast precursor cells in patients with rheumatoid arthritis and ankylosing spondylitis. AB - OBJECTIVE: To examine the effects of infliximab on bone resorption by osteoclast precursor cells (OCPs) in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and to compare the results with changes in disease activity. METHODS: Before and during 24 weeks of infliximab treatment, peripheral blood mononuclear cells of 9 RA and 10 AS patients were seeded onto ivory wafers and adherent cells, including OCPs, were grown in medium promoting osteoclast differentiation. Bone resorption was evaluated morphometrically and correlated to disease activity. A total of 19 healthy individuals were studied in parallel. In addition, biochemical bone markers were assessed in all patients at baseline and after 24 weeks. RESULTS: OCPs from RA patients showed a higher bone resorption at baseline when compared to AS patients. Blocking of tumour necrosis factor (TNF)alpha with infliximab resulted in a strong reduction of bone resorption by OCPs in both cohorts and occurred faster in RA compared to AS patients. This inhibition coincided with a reduction of clinical disease activity in both patient cohorts and with an increase of serum osteocalcin levels and a relative decrease of collagen crosslinks in RA compared to AS patients. CONCLUSION: These results provide an explanation on the cellular level for the anticatabolic effect of TNF neutralisation on bone. The variation in the kinetics of bone resorption by the OCPs in patients with RA and AS suggests disease-specific differences in the type or in the preactivation of OCPs. PMID- 17720726 TI - Lower limb enthesopathy in patients with psoriasis without clinical signs of arthropathy: a hospital-based case-control study. AB - BACKGROUND: Psoriasis is associated with a form of spondyloarthropathy in 10-30% of cases. A major feature of psoriatic arthritis is enthesitis. In some patients with psoriasis the presence of enthesitis could be underdiagnosed. OBJECTIVE: To investigate the presence of lower limbs entheseal abnormalities in patients with chronic plaque psoriasis without signs and symptoms of psoriatic arthritis. METHODS: Thirty patients with psoriasis and 30 controls underwent ultrasonographic evaluation of Achilles, quadriceps, patellar entheses and plantar aponeurosis. Ultrasonographic findings were scored according to the Glasgow Ultrasound Enthesitis Scoring System (GUESS). RESULTS: Mean GUESS score was significantly higher in patients with psoriasis as compared with controls: 7.9 (0.6) vs 2.9 (0.3); p<0.0001. In particular, the thickness of all tendons examined was significant higher in cases than in controls (p<0.0001), as well as the number of enthesophytes in all sites examined. In both cases and controls, the GUESS score was directly correlated with age (r = 0.22; p = 0.008), body mass index (r = 0.23, p = 0.0067) and waist circumference (r = 0.17; p = 0.02). In contrast, the GUESS score was not correlated with the duration and severity of psoriasis according to the Psoriasis Area and Severity Index (r = 0.03; p = 0.8) and body surface area involvement (r = 0.07; p = 0.6). CONCLUSIONS: Entheseal abnormalities can be documented by ultrasonography in clinically asymptomatic patients with psoriasis. These findings could be related to a subclinical entheseal psoriatic inflammation. We suggest close follow-up of patients with psoriasis with entheseal abnormalities for early diagnosis of psoriatic arthritis. PMID- 17720727 TI - Speeding the recovery from ultraslow inactivation of voltage-gated Na+ channels by metal ion binding to the selectivity filter: a foot-on-the-door? AB - Slow inactivated states in voltage-gated ion channels can be modulated by binding molecules both to the outside and to the inside of the pore. Thus, external K(+) inhibits C-type inactivation in Shaker K(+) channels by a "foot-in-the-door" mechanism. Here, we explore the modulation of a very long-lived inactivated state, ultraslow inactivation (I(US)), by ligand binding to the outer vestibule in voltage-gated Na(+) channels. Blocking the outer vestibule by a mutant mu conotoxin GIIIA substantially accelerated recovery from I(US). A similar effect was observed if Cd(2+) was bound to a cysteine engineered to the selectivity filter (K1237C). In K1237C channels, exposed to 30 microM Cd(2+), the time constant of recovery from I(US) was decreased from 145.0 +/- 10.2 s to 32.5 +/- 3.3 s (P < 0.001). Recovery from I(US) was only accelerated if Cd(2+) was added to the bath solution during recovery (V = -120 mV) from I(US), but not when the channels were selectively exposed to Cd(2+) during the development of I(US) (-20 mV). These data could be explained by a kinetic model in which Cd(2+) binds with high affinity to a slow inactivated state (I(S)), which is transiently occupied during recovery from I(US). A total of 50 microM Cd(2+) produced an approximately 8 mV hyperpolarizing shift of the steady-state inactivation curve of I(S), supporting this kinetic model. Binding of lidocaine to the internal vestibule significantly reduced the number of channels entering I(US), suggesting that I(US) is associated with a conformational change of the internal vestibule of the channel. We propose a molecular model in which slow inactivation (I(S)) occurs by a closure of the outer vestibule, whereas I(US) arises from a constriction of the internal vestibule produced by a widening of the selectivity filter region. Binding of Cd(2+) to C1237 promotes the closure of the selectivity filter region, thereby hastening recovery from I(US). Thus, Cd(2+) ions may act like a foot-on the-door, kicking the I(S) gate to close. PMID- 17720728 TI - Noise propagation and scaling in regulation of gonadotrope biosynthesis. AB - Reproductive physiology depends on the control of biosynthesis in the pituitary gonadotrope by hypothalamic gonadotropin-releasing hormone (GnRH). The responses to GnRH include activation of extracellular signal-regulated kinase (ERK) and induction of Egr1. Using population and single cell signaling assays, we investigated the signal and noise transmission through this signaling and gene circuit, analyzing data obtained from 43,775 individual cells in 40 experiments. After exposure to GnRH, phosphorylated ERK (pERK) is elevated in 50% of the cells at 1.7 (SD = 0.3) min. Studies of the cell-to-cell response showed that for both pERK and for Egr1 protein production the mean response (mu) and standard deviation (sigma) within individual cells were linearly related (sigma = kmu) and had similar values of k. To understand the basis for the scaling observed for noise propagation through this system, we determined the relationship between pERK and egr1 mRNA levels induced at varying concentration of GnRH. While both pERK and egr1 mRNA show a saturating sigmoidal relationship to the concentration of GnRH exposure, egr1 mRNA is linearly related to the levels of pERK. These results explain the basis for variation in cellular responses in an important mammalian signaling pathway leading to gene induction. PMID- 17720729 TI - The dynamic orientation of membrane-bound peptides: bridging simulations and experiments. AB - The structural organization in a peptide/membrane supramolecular complex is best described by knowledge of the peptide orientation plus its time-dependent and spatial fluctuations. The static orientation, defined by the peptide tilt and a rotation about its molecular axis, is accessible through a number of spectroscopic methods. However, peptide dynamics, although relevant to understand the functionality of these systems, remains largely unexplored. Here, we describe the orientation and dynamics of Trp-flanked and Lys-flanked hydrophobic peptides in a lipid bilayer from molecular dynamics simulations. A novel view is revealed, where collective nontrivial distributions of time-evolving and ensemble peptide orientations closely represent the systems as studied experimentally. Such global distributions are broad and unveil the existence of orientational states, which depend on the anchoring mode of interfacial residues. We show that this dynamics modulates (2)H quadrupolar splittings and introduces ambiguity in the analysis of NMR data. These findings demonstrate that structural descriptions of peptide/membrane complexes are incomplete, and in cases even imprecise, without knowledge of dynamics. PMID- 17720730 TI - Effects of hydrophobic surfactant proteins on collapse of pulmonary surfactant monolayers. AB - To determine if hydrophobic surfactant proteins affect the stability of pulmonary surfactant monolayers at an air/water interface, the studies reported here compared the kinetics of collapse for the complete set of lipids in calf surfactant with and without the proteins. Monomolecular films spread at the surface of captive bubbles were compressed at 37 degrees C to surface pressures above 46 mN/m, at which collapse first occurred. The rate of area-compression required to maintain a constant surface pressure was measured to directly determine the rate of collapse. For films with and without the proteins, higher surface pressures initially produced faster collapse, but the rates then reached a maximum and decreased to values <0.04 min(-1) above 53 mN/m. The maximum rate for the lipids with the proteins (1.22 +/- 0.28 min(-1)) was almost twice the value for the lipids alone (0.71 +/- 0.15 min(-1)). Because small increments in surface pressure produced large shifts in the rate close to the fastest collapse, compressions at a series of constant speeds also established the threshold rate required to achieve high surface pressure as an indirect indication of the fastest collapse. Both samples produced a sharply defined threshold that occurred at slightly faster compression with the proteins present, supporting the conclusion of the direct measurements that the proteins produce a faster maximum rate of collapse. Our results indicate that at 47-53 mN/m, the hydrophobic surfactant proteins destabilize the compressed monolayers and tend to limit access to the higher surface pressures at which the lipid films become metastable. PMID- 17720731 TI - Lipoplexes formed by DNA and ferrocenyl lipids: effect of lipid oxidation state on size, internal dynamics, and zeta-potential. AB - The effect of lipid oxidation state on the physical properties of complexes formed by plasmid DNA and the redox-active lipid bis-(11 ferrocenylundecyl)dimethylammonium bromide (BFDMA) is reported. With increasing concentration of BFDMA, the hydrodynamic sizes of complexes formed by BFDMA and DNA (in the presence of 1 mM Li(2)SO(4)) pass through a maximum and the zeta potential changes monotonically from -40 mV to +40 mV. In contrast, complexes formed by oxidized BFDMA and DNA exhibit a minimum in size and maintain a negative zeta-potential with increasing concentration of BFDMA. Angle-dependent dynamic light scattering measurements also reveal the presence of relaxation processes within complexes formed by DNA and oxidized BFDMA that are absent for complexes formed by DNA and reduced BFDMA. These results, when combined, reveal that the amphiphilic nature of reduced BFDMA leads to lipoplexes with physical properties resembling those formed by classical cationic lipids, whereas the interaction of oxidized BFDMA with DNA is similar to that of nonamphiphilic cationic molecules bearing multiple charges (e.g., spermidine). In particular, the negative zeta-potential and measurable presence of DNA chain dynamics within complexes formed by oxidized BFDMA and DNA indicate that these complexes are loosely packed with excess charge due to DNA in their outer regions. These results, when combined with additional measurements performed in OptiMEM reduced serum cell culture medium, lead to the proposition that the strong dependence of transfection efficiency on the oxidation state of BFDMA, as reported previously, is largely a reflection of the substantial change in the zeta-potentials of these complexes with changes in the oxidation state of BFDMA. PMID- 17720732 TI - Fluctuations, pauses, and backtracking in DNA transcription. AB - Transcription is a vital stage in the process of gene expression and a major contributor to fluctuations in gene expression levels for which it is typically modeled as a single-step process with Poisson statistics. However, recent single molecule experiments raise questions about the validity of such a simple single step picture. We present a molecular multistep model of transcription elongation that demonstrates that transcription times are in general non-Poisson distributed. In particular, we model transcriptional pauses due to backtracking of the RNA polymerase as a first passage process. By including such pauses, we obtain a broad, heavy-tailed distribution of transcription elongation times, which can be significantly longer than would be otherwise. When transcriptional pauses result in long transcription times, we demonstrate that this naturally leads to bursts of mRNA production and non-Poisson statistics of mRNA levels. These results suggest that transcriptional pauses may be a significant contributor to the variability in transcription rates with direct implications for noise in cellular processes as well as variability between cells. PMID- 17720733 TI - Effect of local anesthetic lidocaine on electrostatic properties of a lipid bilayer. AB - The influence of the local anesthetic lidocaine on electrostatic properties of a lipid membrane bilayer was studied by molecular dynamics simulations. The electrostatic dipole potential, charge densities, and orientations of the headgroup angle have been examined in the presence of different amounts of charged or uncharged forms of lidocaine. Important changes in the membrane properties caused by the presence of both forms of lidocaine are presented and discussed. Our simulations have shown that both charged and uncharged lidocaine cause almost the same increase in the electrostatic potential in the middle of the membrane, although for different reasons. The increase, approximately 90 mV for 9 mol % of lidocaine and 220 mV for 28 mol % of lidocaine, is of a size that may affect the functioning of voltage-gated ion channels. PMID- 17720734 TI - Time and length scales of autocrine signals in three dimensions. AB - A model of autocrine signaling in cultures of suspended cells is developed on the basis of the effective medium approximation. The fraction of autocrine ligands, the mean and distribution of distances traveled by paracrine ligands before binding, as well as the mean and distribution of the ligand lifetime are derived. Interferon signaling by dendritic immune cells is considered as an illustration. PMID- 17720735 TI - Granulocyte colony-stimulating factor production and rapid progression of gastric cancer after histological change in the tumor. AB - Granulocyte colony-stimulating factor (G-CSF)-producing malignancies are thought to be rare and associated with advanced disease and poor prognosis. Here, we report on a 77-year-old patient with G-CSF-producing gastric cancer. We observed this patient from the stage prior to the diagnosis of gastric cancer when leukocyte count was normal to the stage of advanced disease associated with remarkable leukocytosis. Immunohistochemical analysis demonstrated G-CSF expression in the advanced-stage, poorly differentiated adenocarcinoma, but not in the early-stage, well-differentiated adenocarcinoma. G-CSF receptor was not detected to be expressed in the advanced-stage tumor. Based on these results it appears that a histological change in the tumor may influence G-CSF production and the concomitant rapid progression in gastric cancer. PMID- 17720736 TI - Efficacy and safety of an irinotecan plus bolus 5-fluorouracil and L-leucovorin regimen for metastatic colorectal cancer in Japanese patients: experience in a single institution in Japan. AB - BACKGROUND: Short-term infusion of 5-fluorouracil with leucovorin in combination with irinotecan or oxaliplatin has been considered as standard treatment for metastatic colorectal cancer. However, until infusion of 5-fluorouracil regimens and oxaliplatin was approved for the treatment of metastatic colorectal cancer in Japan early in 2005, combination of irinotecan with bolus 5 fluorouracil/leucovorin had been the standard treatment. This retrospective study evaluates the efficacy and safety of a modified irinotecan with bolus 5 fluorouracil/leucovorin regimen in Japanese colorectal cancer patients. METHODS: Forty-six patients untreated with chemotherapy for metastatic colorectal cancer received a modified form of the irinotecan with bolus 5-fluorouracil/leucovorin regimen, consisting of intravenous irinotecan (100 mg/m2) and l-leucovorin (10 mg/m2), and then 5-fluorouracil 500 mg/m2 as an intravenous bolus infusion, weekly for 4 weeks, repeated every 6 weeks until progression or unacceptable toxicity. RESULTS: The overall response rate was 48% (95% confidence interval, 34 62%), and 48% of patients had stable disease. Median progression-free survival was 8.3 months and overall survival was 20.3 months. The incidence of grade 3 or 4 toxicity was as follows: neutropenia, 50%; diarrhea, 4%; fatigue, 13%; nausea, 7%; and vomiting, 7%. Neither treatment-related nor all-cause mortality occurred within 60 days of chemotherapy initiation. Despite the limited availability of oxaliplatin, 29 patients received an oxaliplatin-based regimen after progression. CONCLUSION: A modified irinotecan plus bolus 5-fluorouracil/l-leucovorin regimen was an active and well-tolerated regimen in Japanese patients with advanced colorectal cancer, showing a different toxicity profile from Western patients. PMID- 17720737 TI - Single-agent docetaxel in patients with platinum-refractory metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN). AB - BACKGROUND: The objective of this retrospective study was to investigate the efficacy and tolerability of single-agent docetaxel in patients with platinum refractory squamous cell carcinoma of the head and neck (SCCHN). METHODS: Platinum-refractory disease was defined as cancer with documented tumor progression during platinum-based treatment or recurrence within 6 months after platinum-based chemoradiotherapy. Patients fulfilling the following criteria were enrolled: histologically confirmed SCCHN, excluding nasopharyngeal cancer; measurable metastatic lesions as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST); and platinum-refractory disease. Docetaxel (60 mg/m2) was administered every 3-4 weeks and continued unless there was evidence of disease progression or unacceptable toxicity. RESULTS: Twenty patients were recruited. Overall response rate was 10% (2/20) and tumor control rate was 25% (5/20). Median progression-free and median overall survival times were 1.7 and 4.6 months, respectively. The most common hematological toxicities were leucopenia (grade 4: 35%) and neutropenia (grade 4: 30%). Grade 3 febrile neutropenia and grade 3 mucositis (functional/symptomatic) each occurred in two patients (10%). One fatal bleeding occurred during this treatment, however, the relation between this event and docetaxel was unlikely. Median inpatient period during treatment was 5.4 days (range, 0-50 days). CONCLUSION: A single-agent docetaxel regimen appeared to offer an acceptable clinical profile in patients with platinum refractory SCCHN. PMID- 17720738 TI - Phase I/II study of CPT-11 plus UFT in patients with advanced/recurrent colorectal cancer: Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG): Protocol 0102. AB - OBJECTIVE: The primary objective of this study was to explore the efficacy and safety of combined chemotherapy with CPT-11 and UFT in patients with advanced/metastatic colorectal cancer. METHODS: Twenty-two patients with metastatic colorectal cancer were enrolled in the phase I trial and 35 patients (including eight patients treated at level 4 during phase I) were evaluated in the phase II trial. Treatment consisted of two 35-day cycles of combination chemotherapy with CPT-11 and UFT. During phase I, CPT-11 was administered on days 1 and 15 as an intravenous infusion over 90 min at four different dose levels, starting from a dose of 80 mg/m2 (level 1). During phase II, the dose of CPT-11 was fixed at 150 mg/m2 based on the results of the phase I study. UFT was administered orally at a fixed dose of 300 mg/m2 on days 1-28, followed by a 1 week drug holiday, during each course (35 days). RESULTS: The maximum tolerated dose (MTD) of CPT-11 was determined to be 150 mg/m2 during the phase I trial. The major toxicities detected during phase II in 35 patients receiving CPT-11 at this recommended dose were grade 3/4 neutropenia in nine patients (25.7%) and grade 3/4 anorexia in six patients (11.4%). No severe adverse events occurred. The overall response rate and the median overall survival time was 22.9% (8/35) and 23.9 months for all patients, respectively. For pre-treated patients they were 26.3% (5/19) and 25.1 months, respectively. CONCLUSION: This combination of CPT 11 and UFT is considered to be both feasible and relatively safe. The response rate of the patients receiving CPT-11 at a dose of 150 mg/m2 was comparable to that reported previously for 5-FU-based regimens coupled with CPT-11, and this regimen can probably be beneficial for patients with pre-treated advanced colorectal cancer on an outpatient basis. PMID- 17720740 TI - Hospital procedure volume and survival of cancer patients in Osaka, Japan: a population-based study with latest cases. AB - BACKGROUND: Recent studies reported that hospital procedure volume (i.e. volume of patients per hospital receiving a particular treatment)was directly proportional to cancer survival; however the degree of association might be different according to the primary tumor site, extent of disease and year of diagnosis. We performed a systematical examination of survivals by hospital procedure volume according to the primary site with inclusion of latest cases in Osaka, Japan. METHODS: Individual data on reported cancer cases with active follow-up information and diagnosis between 1994 and 1998 were retrieved from Osaka Cancer Registry's database. The analysed primary sites included oesophagus, stomach, large bowel, liver, gall bladder, pancreas, lung, breast, uterus, ovary, prostate, bladder and lymphoma. Hospitals were ranked as high-, medium-, low- and very low-volume hospitals for every primary site by dividing the number of cancer patients who received treatment in hospitals into four quartiles. RESULTS: The primary sites could be classified into three categories based on the association between hospital procedure volume and cancer survival: In type 1, a better survival was associated with a higher procedure volume as for oesophagus, liver, lung, ovary, prostate, or lymphoma; in type 2, a better survival was associated with a higher procedure volume but there was no significant difference in survival between high- and medium-volume hospitals as for uterus; and in type 3, there was no significant difference in survival among high-, medium- and low volume hospitals as for stomach, large bowel, gall bladder, pancreas, breast, or bladder sites. CONCLUSIONS: A higher procedure volume was generally associated with a better survival; however, this association could be classified into three types according to the primary site. PMID- 17720739 TI - Antegrade radical retropubic prostatectomy with preliminary ligation of vascular pedicles in 614 consecutive patients. AB - BACKGROUND: We present our procedure of antegrade radical retropubic prostatectomy with preliminary ligation of vascular pedicles and assess the time trends of patient characteristics, surgical and oncological outcome in 614 consecutive patients in a single institution over a 12-year period. METHODS: From April 1994 to December 2005, 614 consecutive Japanese patients with cT1-3N0M0 prostate cancer underwent antegrade radical prostatectomy with preliminary ligation of vascular pedicles (dorsal vein complex and prostatic pedicles) prior to the tumor manipulation. Biochemical progression is defined as prostate specific antigen value over 0.2 ng/ml or the initiation of therapy after surgery. Biochemical progression-free, cancer-specific and overall survival curves were calculated by the Kaplan-Meier method. RESULTS: During the study period pre operative PSA, clinical T stage, duration of surgery, amount of estimated blood loss have decreased. Pathological stage showed a significant downward migration and the rate of positive surgical margin has also decreased. At a mean follow-up of 48 months, 21 men were dead including eight who died of prostate cancer. Overall and cancer-specific survival rates were 97/99% at 5 years and 89/95% at 10 years, respectively. Neoadjuvant hormonal treatment had no beneficial impact on oncological outcome of patients regardless of clinical stage. In 370 patients treated surgically alone, cancer-specific and biochemical progression-free survival rates were 99.6/80.5% at 5 years and 97.9/73.3% at 10 years for patients with clinical T1/2 disease and 95.5/41.9% at 5 years and 87.5/41.9% at 10 years for those with T3 disease, respectively. In the 370 patients biochemical progression-free survival has been significantly improved over the 12-year period (P < 0.0001). CONCLUSIONS: Antegrade radical prostatectomy with preliminary ligation of vascular pedicles can be performed with excellent oncological outcome. PMID- 17720741 TI - A case of cholangiocarcinoma mimicking inflammatory pseudotumor. PMID- 17720742 TI - Comparison of time trends in prostate cancer incidence (1973 1997) in East Asia, Europe and USA, from Cancer Incidence in Five Continents Vols IV VIII. PMID- 17720743 TI - Cocaine- and amphetamine-regulated transcript (CART) peptide as an in vivo regulator of cardiac function in Rana ridibunda frog. AB - The aim of this study was to investigate the effect of CART peptide on cardiac performance and on the physiological signalling pathways involved using Rana ridibunda frog heart preparations in vivo. The CART peptide, when injected into the venous sinus, significantly and reproducibly increased the force of frog heart contractions by up to 33.0 +/- 6.4% during the first 15 min after its application but did not influence the chronotropic activity of the frog heart. The positive inotropic effect was entirely blocked by prazosin, pertussis toxin, R(p)-adenosine 3',5'-cyclic monophosphorothioate, autosauvagine 30 or metyrapone, as well as by extirpation of the pituitary gland, functional elimination of the inter-renal glands and long-lasting starvation, and was not observed on isolated heart preparations. Propranolol and double pithing were without significant effect on this phenomenon. It was concluded that: (i) CART peptide, administered to frogs in vivo, increases the force of heart contractions; (ii) this effect of the peptide is exerted via activation of the hypothalamic-pituitary-inter-renal gland axis through a corticoliberin-sensitive mechanism; (iii) CART augments the pumping function of the heart via a corticosteroid-dependent potentiation of myocardial alpha(1)-adrenoreceptors signalling; and (iv) prolonged food deprivation abolishes the positive inotropic effect of CART, suggesting the participation of endogenous CART in the physiological adaptation of the circulatory system to limitations of energy consumption. PMID- 17720744 TI - The effects of tertiapin-Q on responses of the sinoatrial pacemaker of the guinea pig heart to vagal nerve stimulation and muscarinic agonists. AB - Using Langendorff preparations of the guinea-pig heart, we have examined the participation of the acetylcholine (ACh)-activated potassium channel, IK,ACh, in the bradycardia produced by electrical stimulation of the vagus (parasympathetic) nerve and muscarinic agonists (ACh and bethanecol, bolus i.a.). Hearts from young animals (160-250 g) were perfused with Krebs-Henseleit solution, and pacemaker frequency was determined from the P wave of an ECG. Tertiapin-Q was used to block IK,ACh. Vagal stimulation (10 s trains at 2, 5 and 10 Hz) produced graded reductions in atrial rate that were substantially attenuated, and to a similar extent, by 300 nm and 1 microm tertiapin-Q (to 0.42 +/- 0.12, mean +/- s.d., of the control values; P < 0.001). Acetylcholine (3 nmol) produced brief graded bradycardias that were also attenuated by tertiapin-Q (0.24 +/- 0.24; P = 0.006). Similar results were obtained when experiments were repeated in 2 mm Cs+ (to block the hyperpolarization-activated pacemaker current). Bethanecol (30, 50 and 70 nmol), a muscarinic agonist with no appreciable nicotinic activity, produced sustained bradycardias that were attenuated by 300 nm tertiapin-Q (0.36 +/- 0.21; P < 0.0001). The responses to vagal stimulation and ACh developed more slowly in tertiapin-Q, indicating that a rapidly acting mechanism had been blocked. Responses to vagal stimulation were faster in 2 mm Cs+. Together, these observations show that ACh released from parasympathetic nerve varicosities exerts a considerable part of its effect on the pacemaker by activating IK,ACh and acts in a manner not readily distinguishable from that of directly applied muscarinic agonists. PMID- 17720745 TI - Association between KCNJ11 E23K genotype and cardiovascular and glucose metabolism phenotypes in older men and women. AB - Our objective was to investigate the relationship between the E23K genetic variant in the KCNJ11 gene, which encodes for the Kir6.2 subunit of the inward rectifier K+ channel family, and glucose and insulin metabolism and cardiovascular (CV) function in the sedentary state and their responses to exercise training. Two hundred and fourteen healthy sedentary men and women aged 50-75 years old and free of CV disease and type 2 diabetes underwent baseline testing (maximal oxygen consumption (Vo2max), body composition and glucose tolerance). One hundred and sixty-three of them repeated these tests after 24 weeks of exercise training while on a low-fat diet. At baseline, age, height, body fat, resting systolic blood pressure and all glucose and insulin metabolism markers did not differ among E23K genotype groups. In women at baseline, E23K genotype was associated with body weight, body mass index, Vo2max (ml kg(-1) min( 1), l min(-1)) and maximal minute ventilation. In men at baseline, E23K genotype was significantly associated with maximal heart rate, maximal respiratory exchange ratio and diastolic blood pressure at rest. Numerous glucose and insulin metabolism and CV function phenotypes changed significantly with exercise training in the total population. The E23K genotype did not significantly influence any of these training-induced changes. Thus, the common E23K genetic variant at the KCNJ11 gene locus was significantly associated with CV function in the untrained state, although the associations appear to differ between men and women. However, this variant has no significant effect on training-induced CV and glucose and insulin metabolism adaptations. PMID- 17720746 TI - Influence of heat stress on the reactivity of isolated chicken carotid artery to vasoactive agents. AB - Cerebral ischaemia is considered to be an important cause of central nervous system dysfunction in heat stress. We hypothesized that heat stress would alter the reactivity of isolated carotid artery to vasoactive agents. Carotid arteries were isolated from broiler chickens maintained either at 23-24 degrees C with 55 65% humidity (control conditions) or exposed to 40 +/- 1 degrees C with 35% humidity for 4 h (heat stress). Contractions were elicited with vasoconstrictors such as 5-HT, phenylephrine, guanfacine and CaCl(2) (K(+)-depolarized) in endothelium-denuded arterial rings. Heat stress significantly increased the potency of 5-HT, but had no effect on the sensitivity of the vessel to phenylephrine or guanfacine. In contrast, it markedly decreased the potency and efficacy of CaCl(2). Vasodilator responses to ACh (endothelium-intact) and sodium nitroprusside (endothelium-denuded), however, were unaffected. Although cyclopiazonic acid (10 microm) significantly decreased 5-HT responses in both the conditions, the agonist was still more potent in heat stress. Extracellular Ca(2)(+) removal had no effect on contractions caused by 5-HT in control conditions, but it significantly decreased the agonist potency in heat stress. Interestingly, nifedipine (1 microm) markedly inhibited 5-HT-induced contractions both in control conditions and in heat stress, implying an inhibitory effect on both Ca(2)(+) influx and release. Thus, nifedipine had a markedly greater inhibitory effect on 5-HT-induced contractions in heat stress compared with control conditions. The results suggest that heat stress increased the vasoconstrictor responses to 5-HT by a mechanism that involved extracellular Ca(2)(+) influx through nifedipine-sensitive L-type calcium channels. PMID- 17720747 TI - Neuroendocrine control of T cell development in mammals: role of growth hormone in modulating thymocyte migration. AB - The thymus gland is a primary lymphoid organ, in which bone-marrow-derived T cell precursors undergo differentiation, eventually leading to migration of positively selected cells to the peripheral lymphoid organs. This differentiation occurs along with cell migration in the context of the thymic microenvironment, a three dimensional network formed by epithelial cells, macrophages, dendritic cells, fibroblasts and extracellular matrix components. A series of data clearly shows that growth hormone (GH) pleiotropically modulates thymic functions. For example, GH upregulates proliferation of thymocytes and thymic epithelial cells. Accordingly, GH-transgenic mice, as well as animals and humans treated with exogenous GH, exhibit an enhanced cellularity in the organ. Growth hormone stimulates the secretion of thymic hormones, cytokines and chemokines by the thymic microenvironment, as well as the production of extracellular matrix proteins, leading to an increase in thymocyte migratory responses and intrathymic traffic of developing T cells. In addition, GH stimulates the in vivo export of thymocytes from the organ, as ascertained by studies with intrathymic injection of GH in normal mice and with GH-transgenic mice. Moreover, since GH is produced by thymocytes and thymic epithelial cells, which express GH receptors, we should consider that, in addition to the classic endocrine pathway, the GH control of the thymus may include an autocrine/paracrine pathway. Finally, since GH promotes a replenishment of the thymus and an increase of thymocyte export, it could be envisioned as a potential adjuvant therapeutic agent in the treatment of immunodeficiencies associated with thymic atrophy. PMID- 17720748 TI - Regulation of tissue perfusion in mammals by hypoxia-inducible factor 1. AB - The regulation of tissue perfusion is a major mechanism by which oxygen homeostasis is maintained. Hypoxia-inducible factor 1 (HIF-1) is a transcriptional regulator that mediates adaptive responses to reduced partial pressure of O(2) in all metazoan species. In mammals, HIF-1 promotes angiogenesis, arteriogenesis and vasculogenesis through the production of multiple angiogenic growth factors in ischaemic tissue and by cell-autonomous effects on endothelial cells and bone marrow-derived angiogenic cells. Administration of viral vectors encoding constitutively active forms of the HIF 1alpha subunit results in increased tissue perfusion in animal models of ischaemic cardiovascular disease. PMID- 17720749 TI - Repertoires of aggregation-resistant human antibody domains. AB - We recently described a method for the generation of a large human domain antibody repertoire involving combinatorial assembly of CDR building blocks from a smaller repertoire comprising a high frequency of aggregation-resistant antibody domains. Here we show that the frequency of aggregation-resistant domains in the combinatorial repertoire remained high. Furthermore, one of the antigen-binding domains selected from the combinatorial repertoire retained its binding properties through 25 cycles of thermal denaturation, suggesting that antibody domains can be created that rival the heat-resistance of thermophilic proteins such as Taq polymerase. PMID- 17720750 TI - The PASTA server for protein aggregation prediction. AB - Many different proteins aggregate into amyloid fibrils characterized by cross beta structure. beta-strands contributed by distinct protein molecules are generally found in a parallel in-register alignment. Here, we describe the web server for a novel algorithm, prediction of amyloid structure aggregation (PASTA), to predict the most aggregation-prone portions and the corresponding beta-strand inter-molecular pairing for a given input sequence. PASTA was previously shown to yield results in excellent agreement with available experimental observations, when tested on both natively unfolded and structured proteins. The web server and downloadable source code are freely accessible from the URL: http://protein.cribi.unipd.it/pasta/. PMID- 17720751 TI - C-terminus engineering of soybean proglycinin: improvement of emulsifying properties. AB - Introduction of the extension region of beta-conglycinin alpha' subunit at the C terminus of proglycinin A1aB1b results in the improvement of its emulsifying properties. To understand the basic for such improvement, we introduced the alpha' and alpha extension regions to the A2B1a C-terminus, and the alpha extension and A5A4B3 hypervariable regions, and an oligopeptide composed of 20 negatively or positively charged residues to the A1aB1b C-terminus, creating A2B1aalpha', A2B1aalpha, and A1aB1balpha, A1aB1bA4IV, A1aB1bNeg and A1aB1bPos, respectively. All the modified versions were produced in Escherichia coli. Their molecular size, thermal stability, surface hydrophobicity, solubility and emulsifying ability were studied. Analyses of molecular size and thermal stability suggested that all the modified versions formed the proper conformation similar to that of the wild type (WT). Solubility was intrinsic to each mutant. At ionic strength 0.5, the emulsifying abilities of all mutants were better than that of the WT except A1aB1bPos and A1aB1bNeg, and at ionic strength 0.08, all mutants especially A1aB1bPos exhibited better emulsifying ability than did the WT. The order of stability of the emulsion at both ionic strengths (0.08 and 0.5) was A1aB1balpha >or= A2B1aalpha > A1aB1balpha' >or= A2B1aalpha' >> A1aB1bPos > A1aB1bA4IV >or= A1aB1bNeg > A1aB1b, A2B1a. These results indicate that the emulsion stability of proglycinin mutants depends on length and hydropathy profile of the polypeptides added to the C-terminus of proglycinin. PMID- 17720752 TI - TRBO: a high-efficiency tobacco mosaic virus RNA-based overexpression vector. AB - Transient expression is a rapid, useful approach for producing proteins of interest in plants. Tobacco mosaic virus (TMV)-based transient expression vectors can express very high levels of foreign proteins in plants. However, TMV vectors are, in general, not efficiently delivered to plant cells by agroinfection. It was determined that agroinfection was very efficient with a 35S promoter-driven TMV replicon that lacked the TMV coat protein gene sequence. This coat protein deletion vector had several useful features as a transient expression system, including improved ease of use, higher protein expression rates, and improved biocontainment. Using this TMV expression vector, some foreign proteins were expressed at levels of 3 to 5 mg/g fresh weight of plant tissue. It is proposed that this new transient expression vector will be a useful tool for expressing recombinant proteins in plants for either research or production purposes. PMID- 17720753 TI - Ethylene is one of the key elements for cell death and defense response control in the Arabidopsis lesion mimic mutant vad1. AB - Although ethylene is involved in the complex cross talk of signaling pathways regulating plant defense responses to microbial attack, its functions remain to be elucidated. The lesion mimic mutant vad1-1 (for vascular associated death), which exhibits the light-conditional appearance of propagative hypersensitive response-like lesions along the vascular system, is a good model for studying the role of ethylene in programmed cell death and defense. Here, we demonstrate that expression of genes associated with ethylene synthesis and signaling is enhanced in vad1-1 under lesion-promoting conditions and after plant-pathogen interaction. Analyses of the progeny from crosses between vad1-1 plants and either 35SERF1 transgenic plants or ein2-1, ein3-1, ein4-1, ctr1-1, or eto2-1 mutants revealed that the vad1-1 cell death and defense phenotypes are dependent on ethylene biosynthesis and signaling. In contrast, whereas vad1-1-dependent increased resistance was abolished by ein2, ein3, and ein4 mutations, positive regulation of ethylene biosynthesis (eto2-1) or ethylene responses (35SERF1) did not exacerbate this phenotype. In addition, VAD1 expression in response to a hypersensitive response-inducing bacterial pathogen is dependent on ethylene perception and signaling. These results, together with previous data, suggest that VAD1 could act as an integrative node in hormonal signaling, with ethylene acting in concert with salicylic acid as a positive regulator of cell death propagation. PMID- 17720754 TI - Reverse genetics of floral scent: application of tobacco rattle virus-based gene silencing in Petunia. AB - Floral fragrance is responsible for attracting pollinators as well as repelling pathogens and pests. As such, it is of immense biological importance. Molecular dissection of the mechanisms underlying scent production would benefit from the use of model plant systems with big floral organs that generate an array of volatiles and that are amenable to methods of forward and reverse genetics. One candidate is petunia (Petunia hybrida), which has emerged as a convenient model system, and both RNAi and overexpression approaches using transgenes have been harnessed for the study of floral volatiles. Virus-induced gene silencing (VIGS) is characterized by a simple inoculation procedure and rapid results relative to transgenesis. Here, we demonstrate the applicability of the tobacco rattle virus based VIGS system to studies of floral scent. Suppression of the anthocyanin pathway via chalcone synthase silencing was used as a reporter, allowing easy visual identification of anthocyaninless silenced flowers/tissues with no effect on the level of volatile emissions. Use of tobacco rattle virus constructs containing target genes involved in phenylpropanoid volatile production, fused to the chalcone synthase reporter, allowed simple identification of flowers with suppressed activity of the target genes. The applicability of VIGS was exemplified with genes encoding S-adenosyl-l-methionine:benzoic acid/salicylic acid carboxyl methyltransferase, phenylacetaldehyde synthase, and the myb transcription factor ODORANT1. Because this high-throughput reverse-genetics approach was applicable to both structural and regulatory genes responsible for volatile production, it is expected to be highly instrumental for large-scale scanning and functional characterization of novel scent genes. PMID- 17720755 TI - Posttranscriptional regulation of high-affinity sulfate transporters in Arabidopsis by sulfur nutrition. AB - High-affinity sulfate transporters SULTR1;1 and SULTR1;2 are expressed at epidermis and cortex of Arabidopsis (Arabidopsis thaliana) roots during sulfur limitation. Here, we report that SULTR1;1 and SULTR1;2 are two essential components of the sulfate uptake system in roots and are regulated at posttranscriptional levels together with the previously reported transcriptional control. Double knockout of SULTR1;1 and SULTR1;2 by T-DNA insertion gene disruption resulted in complete lack of sulfate uptake capacity and severely affected plant growth under low-sulfur conditions. Expression of epitope-tagged proteins SULTR1;1mycHis and SULTR1;2mycHis, under the control of the cauliflower mosaic virus 35S promoter, rescued the uptake of sulfate and the growth of the sultr1;1 sultr1;2 double knockout mutant. The recovery of the double knockout phenotypes was attributable to the posttranscriptional accumulation of sulfate transporter proteins that derive from the epitope-tagged transgenic constructs. Both SULTR1;1mycHis and SUTLR1;2mycHis mRNAs were predominantly found in roots and slightly induced by long-term sulfur limitation. SULTR1;1mycHis and SULTR1;2mycHis proteins were found exclusively in roots, and significantly accumulated by sulfur limitation, correlating with the induction of sulfate uptake activities. In the time course of short-term sulfate starvation treatment, SULTR1;1mycHis and SULTR1;2mycHis proteins were significantly accumulated during the 8- to 72-h period, causing substantial induction of sulfate uptake activities, while their corresponding mRNAs were expressed constantly around the initial levels, except for the transient induction in the first 2 h. This study suggested the importance of root-specific and sulfur deficiency-inducible accumulation of SULTR1;1 and SULTR1;2 sulfate transporter proteins for the acquisition of sulfate from low-sulfur environment. PMID- 17720756 TI - Regulation of one-carbon metabolism in Arabidopsis: the N-terminal regulatory domain of cystathionine gamma-synthase is cleaved in response to folate starvation. AB - In all organisms, control of folate homeostasis is of vital importance to sustain the demand for one-carbon (C1) units that are essential in major metabolic pathways. In this study we induced folate deficiency in Arabidopsis (Arabidopsis thaliana) cells by using two antifolate inhibitors. This treatment triggered a rapid and important decrease in the pool of folates with significant modification in the distribution of C1-substituted folate coenzymes, suggesting an adaptive response to favor a preferential shuttling of the flux of C1 units to the synthesis of nucleotides over the synthesis of methionine (Met). Metabolic profiling of folate-deficient cells indicated important perturbation of the activated methyl cycle because of the impairment of Met synthases that are deprived of their substrate 5-methyl-tetrahydrofolate. Intriguingly, S-adenosyl Met and Met pools declined during the initial period of folate starvation but were further restored to typical levels. Reestablishment of Met and S-adenosyl Met homeostasis was concomitant with a previously unknown posttranslational modification that consists in the removal of 92 amino acids at the N terminus of cystathionine gamma-synthase (CGS), the first specific enzyme for Met synthesis. Rescue experiments and analysis of different stresses indicated that CGS processing is specifically associated with perturbation of the folates pool. Also, CGS processing involves chloroplastic serine-type proteases that are expressed in various plant species subjected to folate starvation. We suggest that a metabolic effector, to date unidentified, can modulate CGS activity in vivo through an interaction with the N-terminal domain of the enzyme and that removal of this domain can suppress this regulation. PMID- 17720758 TI - Ancestral chromosomal blocks are triplicated in Brassiceae species with varying chromosome number and genome size. AB - The paleopolyploid character of genomes of the economically important genus Brassica and closely related species (tribe Brassiceae) is still fairly controversial. Here, we report on the comparative painting analysis of block F of the crucifer Ancestral Karyotype (AK; n = 8), consisting of 24 conserved genomic blocks, in 10 species traditionally treated as members of the tribe Brassiceae. Three homeologous copies of block F were identified per haploid chromosome complement in Brassiceae species with 2n = 14, 18, 20, 32, and 36. In high polyploid (n >or= 30) species Crambe maritima (2n = 60), Crambe cordifolia (2n = 120), and Vella pseudocytisus (2n = 68), six, 12, and six copies of the analyzed block have been revealed, respectively. Homeologous regions resembled the ancestral structure of block F within the AK or were altered by inversions and/or translocations. In two species of the subtribe Zillineae, two of the three homeologous regions were combined via a reciprocal translocation onto one chromosome. Altogether, these findings provide compelling evidence of an ancient hexaploidization event and corresponding whole-genome triplication shared by the tribe Brassiceae. No direct relationship between chromosome number and genome size variation (1.2-2.5 pg/2C) has been found in Brassiceae species with 2n = 14 to 36. Only two homeologous copies of block F suggest a whole-genome duplication but not the triplication event in Orychophragmus violaceus (2n = 24), and confirm a phylogenetic position of this species outside the tribe Brassiceae. Chromosome duplication detected in Orychophragmus as well as chromosome rearrangements shared by Zillineae species demonstrate the usefulness of comparative cytogenetics for elucidation of phylogenetic relationships. PMID- 17720757 TI - Diversity of acetyl-coenzyme A carboxylase mutations in resistant Lolium populations: evaluation using clethodim. AB - The acetyl-coenzyme A carboxylase (ACCase)-inhibiting cyclohexanedione herbicide clethodim is used to control grass weeds infesting dicot crops. In Australia clethodim is widely used to control the weed Lolium rigidum. However, clethodim resistant Lolium populations have appeared over the last 5 years and now are present in many populations across the western Australian wheat (Triticum aestivum) belt. An aspartate-2078-glycine (Gly) mutation in the plastidic ACCase enzyme has been identified as the only known mutation endowing clethodim resistance. Here, with 14 clethodim-resistant Lolium populations we revealed diversity and complexity in the molecular basis of resistance to ACCase inhibiting herbicides (clethodim in particular). Several known ACCase mutations (isoleucine-1781-leucine [Leu], tryptophan-2027-cysteine [Cys], isoleucine-2041 asparagine, and aspartate-2078-Gly) and in particular, a new mutation of Cys to arginine at position 2088, were identified in plants surviving the Australian clethodim field rate (60 g ha(-1)). Twelve combination patterns of mutant alleles were revealed in relation to clethodim resistance. Through a molecular, biochemical, and biological approach, we established that the mutation 2078-Gly or 2088-arginine endows sufficient level of resistance to clethodim at the field rate, and in addition, combinations of two mutant 1781-Leu alleles, or two different mutant alleles (i.e. 1781-Leu/2027-Cys, 1781-Leu/2041-asparagine), also confer clethodim resistance. Plants homozygous for the mutant 1781, 2078, or 2088 alleles were found to be clethodim resistant and cross resistant to a number of other ACCase inhibitor herbicides including clodinafop, diclofop, fluazifop, haloxyfop, butroxydim, sethoxydim, tralkoxydim, and pinoxaden. We established that the specific mutation, the homo/heterozygous status of a plant for a specific mutation, and combinations of different resistant alleles plus herbicide rates all are important in contributing to the overall level of herbicide resistance in genetically diverse, cross-pollinated Lolium species. PMID- 17720759 TI - Optimizing the distribution of resources between enzymes of carbon metabolism can dramatically increase photosynthetic rate: a numerical simulation using an evolutionary algorithm. AB - The distribution of resources between enzymes of photosynthetic carbon metabolism might be assumed to have been optimized by natural selection. However, natural selection for survival and fecundity does not necessarily select for maximal photosynthetic productivity. Further, the concentration of a key substrate, atmospheric CO(2), has changed more over the past 100 years than the past 25 million years, with the likelihood that natural selection has had inadequate time to reoptimize resource partitioning for this change. Could photosynthetic rate be increased by altered partitioning of resources among the enzymes of carbon metabolism? This question is addressed using an "evolutionary" algorithm to progressively search for multiple alterations in partitioning that increase photosynthetic rate. To do this, we extended existing metabolic models of C(3) photosynthesis by including the photorespiratory pathway (PCOP) and metabolism to starch and sucrose to develop a complete dynamic model of photosynthetic carbon metabolism. The model consists of linked differential equations, each representing the change of concentration of one metabolite. Initial concentrations of metabolites and maximal activities of enzymes were extracted from the literature. The dynamics of CO(2) fixation and metabolite concentrations were realistically simulated by numerical integration, such that the model could mimic well-established physiological phenomena. For example, a realistic steady state rate of CO(2) uptake was attained and then reattained after perturbing O(2) concentration. Using an evolutionary algorithm, partitioning of a fixed total amount of protein-nitrogen between enzymes was allowed to vary. The individual with the higher light-saturated photosynthetic rate was selected and used to seed the next generation. After 1,500 generations, photosynthesis was increased substantially. This suggests that the "typical" partitioning in C(3) leaves might be suboptimal for maximizing the light-saturated rate of photosynthesis. An overinvestment in PCOP enzymes and underinvestment in Rubisco, sedoheptulose-1,7 bisphosphatase, and fructose-1,6-bisphosphate aldolase were indicated. Increase in sink capacity, such as increase in ADP-glucose pyrophosphorylase, was also indicated to lead to increased CO(2) uptake rate. These results suggest that manipulation of partitioning could greatly increase carbon gain without any increase in the total protein-nitrogen investment in the apparatus for photosynthetic carbon metabolism. PMID- 17720760 TI - A novel image-analysis technique for kinematic study of growth and curvature. AB - Kinematic analysis has provided important insights into the biology of growth by revealing the distribution of expansion within growing organs. Modern methods of kinematic analysis have made use of new image-tracking algorithms and computer assisted evaluation, but these methods have yet to be adapted for examination of growth in a variety of plant species or for analysis of graviresponse. Therefore, a new image-analysis program, KineRoot, was developed to study spatio-temporal patterns of growth and curvature of roots. Graphite particles sprinkled on the roots create random patterns that can be followed by image analysis. KineRoot tracks the displacement of patterns created by the graphite particles over space and time using three search algorithms. Following pattern tracking, the edges of the roots are identified automatically by an edge detection algorithm that provides root diameter and root midline. Local growth rate of the root is measured by projecting the tracked points on the midline. From the shape of the root midline, root curvature is calculated. By combining curvature measurement with root diameter, the differential growth ratio between the greater and lesser curvature edges of a bending root is calculated. KineRoot is capable of analyzing a large number of images to generate local root growth and root curvature data over several hours, permitting kinematic analysis of growth and gravitropic responses for a variety of root types. PMID- 17720761 TI - Reduced carbon availability to bacteroids and elevated ureides in nodules, but not in shoots, are involved in the nitrogen fixation response to early drought in soybean. AB - Nitrogen fixation (NF) in soybean (Glycine max L. Merr.) is highly sensitive to soil drying. This sensitivity has been related to an accumulation of nitrogen compounds, either in shoots or in nodules, and a nodular carbon flux shortage under drought. To assess the relative importance of carbon and nitrogen status on NF regulation, the responses to the early stages of drought were monitored with two soybean cultivars with known contrasting tolerance to drought. In the sensitive cultivar ('Biloxi'), NF inhibition occurred earlier and was more dramatic than in the tolerant cultivar ('Jackson'). The carbon flux to bacteroids was also more affected in 'Biloxi' than in 'Jackson', due to an earlier inhibition of sucrose synthase activity and a larger decrease of malate concentration in the former. Drought provoked ureide accumulation in nodules of both cultivars, but this accumulation was higher and occurred earlier in 'Biloxi'. However, at this early stage of drought, there was no accumulation of ureides in the leaves of either cultivar. These results indicate that a combination of both reduced carbon flux and nitrogen accumulation in nodules, but not in shoots, is involved in the inhibition of NF in soybean under early drought. PMID- 17720763 TI - Mammalian skeletal muscle voltage-gated sodium channels are affected by scorpion depressant "insect-selective" toxins when preconditioned. AB - Among scorpion beta- and alpha-toxins that modify the activation and inactivation of voltage-gated sodium channels (Na(v)s), depressant beta-toxins have traditionally been classified as anti-insect selective on the basis of toxicity assays and lack of binding and effect on mammalian Na(v)s. Here we show that the depressant beta-toxins LqhIT2 and Lqh-dprIT3 from Leiurus quinquestriatus hebraeus (Lqh) bind with nanomolar affinity to receptor site 4 on rat skeletal muscle Na(v)s, but their effect on the gating properties can be viewed only after channel preconditioning, such as that rendered by a long depolarizing prepulse. This observation explains the lack of toxicity when depressant toxins are injected in mice. However, when the muscle channel rNa(v)1.4, expressed in Xenopus laevis oocytes, was modulated by the site 3 alpha-toxin LqhalphaIT, LqhIT2 was capable of inducing a negative shift in the voltage-dependence of activation after a short prepulse, as was shown for other beta-toxins. These unprecedented results suggest that depressant toxins may have a toxic impact on mammals in the context of the complete scorpion venom. To assess whether LqhIT2 and Lqh-dprIT3 interact with the insect and rat muscle channels in a similar manner, we examined the role of Glu24, a conserved "hot spot" at the bioactive surface of beta-toxins. Whereas substitutions E24A/N abolished the activity of both LqhIT2 and Lqh-dprIT3 at insect Na(v)s, they increased the affinity of the toxins for rat skeletal muscle channels. This result implies that depressant toxins interact differently with the two channel types and that substitution of Glu24 is essential for converting toxin selectivity. PMID- 17720762 TI - Flavonoids are differentially taken up and transported long distances in Arabidopsis. AB - Flavonoids are synthesized in response to developmental and environmental signals and perform many functions in plants. Arabidopsis (Arabidopsis thaliana) roots grown in complete darkness do not accumulate flavonoids since the expression of genes encoding enzymes of flavonoid biosynthesis is light dependent. Yet, flavonoids accumulate in root tips of plants with light-grown shoots and light shielded roots, consistent with shoot-to-root flavonoid movement. Using fluorescence microscopy, a selective flavonoid stain, and localized aglycone application to transparent testa mutants, we showed that flavonoids accumulated in tissues distal to the application site, indicating uptake and movement systems. This was confirmed by time-course fluorescence experiments and high performance liquid chromatography. Flavonoid applications to root tips resulted in basipetal movement in epidermal layers, with subsequent fluorescence detected 1 cm from application sites after 1 h. Flavonoid application to midroot or cotyledons showed movement of flavonoids toward the root tip mainly in vascular tissue. Naringenin, dihydrokaempferol, and dihydroquercetin were taken up at the root tip, midroot, or cotyledons and traveled long distances via cell-to-cell movement to distal tissues, followed by conversion to quercetin and kaempferol. In contrast, kaempferol and quercetin were only taken up at the root tip. Using ATP-binding cassette (ABC) transporter and H(+)-ATPase inhibitors suggested that a multidrug resistance-associated protein ABCC transporter facilitated flavonoid movement away from the application site. PMID- 17720764 TI - Evidence for an aryl hydrocarbon receptor-mediated cytochrome p450 autoregulatory pathway. AB - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor responsible for mediating the cellular response to the toxic compound 2,3,7,8, tetrachlorodibenzo-p-dioxin. An essential role for the AhR in cellular biology has been established previously, but no high-affinity endogenous ligand has yet been identified. We have confirmed the presence of a putative endogenous ligand(s) in CV-1 cells through transient transfection with various cytochrome P450 isoforms. Expression of cytochromes P450 1A1, 1A2, or 1B1 reduced AhR mediated luciferase reporter activity, whereas cytochrome P450 2E1 exhibited no significant effect. Studies with 2,4,3',5'-tetramethoxystilbene, a potent and specific inhibitor of cytochrome P450 1B1, was able to partially block cytochrome P450 1B1-mediated reduction in reporter gene activity. These results provide evidence of the existence of a possible feedback mechanism in which AhR-regulated cytochromes P450 from the CYP1A and CYP1B families are able to metabolically alter putative endogenous ligand(s). Several experiments were performed to provide initial characterization of these putative endogenous ligands, including electrophoretic mobility shift assay analyses, which demonstrated that these ligands directly activate the AhR. Soluble extracts from various C57BL/6J and Ahr null mouse tissues were also analyzed for the presence of AhR activators. Studies revealed that Ahr-null mouse lung tissue had a 4-fold increase in AhR-mediated reporter activity in cells. Quantitative polymerase chain reaction analysis revealed that lung tissue exhibits relatively high constitutive CYP1A1 mRNA levels. These results suggest that there is an autoregulatory feedback loop between the AhR and cytochrome P450 1A1 in mouse lung. PMID- 17720765 TI - Diminished NO release in chronic hypoxic human endothelial cells. AB - The present study addressed whether chronic hypoxia is associated with reduced nitric oxide (NO) release due to decreased activation of endothelial NO synthase (eNOS). Primary cultures of endothelial cells from human umbilical veins (HUVECs) were used and exposed to different oxygen levels for 24 h, after which NO release, intracellular calcium, and eNOS activity and phosphorylation were measured after 24 h. Direct measurements using a NO microsensor showed that in contrast to 1-h exposure to 5% and 1% oxygen (acute hypoxia), histamine-evoked (10 microM) NO release from endothelial cells exposed to 5% and 1% oxygen for 24 h (chronic hypoxia) was reduced by, respectively, 58% and 40%. Furthermore, chronic hypoxia also lowered the amount and activity of eNOS enzyme. The decrease in activity could be accounted for by reduced intracellular calcium and altered eNOS phosphorylation. eNOS Ser(1177) and eNOS Thr(495) phosphorylations were reduced and increased, respectively, consistent with lowered enzyme activity. Akt kinase, which can phosphorylate eNOS Ser(1177), was also decreased by hypoxia, regarding both total protein content and the phosphorylated (active) form. Moreover, the protein content of beta- actin, which is known to influence the activity of eNOS, was almost halved by hypoxia, further supporting the fall in eNOS activity. In conclusion, chronic hypoxia in HUVECs reduces histamine-induced NO release as well as eNOS expression and activity. The decreased activity is most likely due to changed eNOS phosphorylation, which is supported by decreases in Akt expression and phosphorylation. By reducing NO, chronic hypoxia may accentuate endothelial dysfunction in cardiovascular disease. PMID- 17720766 TI - Tranilast attenuates diastolic dysfunction and structural injury in experimental diabetic cardiomyopathy. AB - Diastolic dysfunction is an increasingly recognized complication of diabetes that develops in relatively young patients as a result of diabetic cardiomyopathy (DCM). With recent advances in echocardiographic technology now permitting the reliable assessment of diastolic function in the rat, we examined cardiac function and structure in diabetic rodents and assessed the effects of intervening with tranilast, an antifibrotic compound that has been shown to attenuate the actions of transforming growth factor-beta (TGF-beta) in cardiac fibroblasts. We also sought to examine the mechanism whereby tranilast inhibits the actions of TGF-beta. Six-week-old heterozygous (mRen-2)27 rats were randomized to receive either streptozotocin or citrate buffer and then further randomized to receive either tranilast (400 mg x kg(-1) x day(-1) by twice daily gavage) or vehicle for another 8 wk. Cell signaling was examined in neonatal cardiac fibroblasts. After 8 wk, diabetic rats showed evidence of impaired diastolic function with reduced early-to-late atrial wave ratio and prolonged deceleration time in association with fibrosis, apoptosis, and hypertrophy (all P < 0.05). Treatment with tranilast prevented the development of diastolic dysfunction and the histopathological features of DCM. While tranilast did not affect Smad phosphorylation, it significantly attenuated TGF-beta-induced p44/42 mitogen-activated protein kinase phosphorylation. PMID- 17720767 TI - Transendothelial flow inhibits neutrophil transmigration through a nitric oxide dependent mechanism: potential role for cleft shear stress. AB - Endothelial cells in vivo are well known to respond to parallel shear stress induced by luminal blood flow. In addition, fluid filtration across endothelium (transendothelial flow) may trigger nitric oxide (NO) production, presumably via shear stress within intercellular clefts. Since NO regulates neutrophil endothelial interactions, we determined whether transendothelial flow regulates neutrophil transmigration. Interleukin-1beta-treated human umbilical vein endothelial cell (HUVEC) monolayers cultured on a polycarbonate filter were placed in a custom chamber with or without a modest hydrostatic pressure gradient (DeltaP, 10 cm H(2)O) to induce transendothelial flow. In other experiments, cells were studied in a parallel plate flow chamber at various transendothelial flows (DeltaP = 0, 5, and 10 cm H(2)O) and luminal flows (shear stress of 0, 1, and 2 dyn/cm(2)). In the absence of luminal flow, transendothelial flow reduced transmigration of freshly isolated human neutrophils from 57% to 14% (P < 0.05) and induced an increase in NO detected with a fluorescent assay (DAF-2DA). The NO synthase inhibitor L-NAME prevented the effects of transendothelial flow on neutrophil transmigration, while a NO donor (DETA/NO, 1 mM) inhibited neutrophil transmigration. Finally, in the presence of luminal flow (1 and 2 dyn/cm(2)), transendothelial flow also inhibited transmigration. On the basis of HUVEC morphometry and measured transendothelial volume flow, we estimated cleft shear stress to range from 49 to 198 dyn/cm(2). These shear stress estimates, while substantial, are of similar magnitude to those reported by others with similar analyses. These data are consistent with the hypothesis that endothelial cleft shear stress inhibits neutrophil transmigration via a NO-dependent mechanism. PMID- 17720769 TI - Assessment of cardiac function with the pressure-volume conductance system following myocardial infarction in mice. AB - Myocardial infarction (MI) is a major cause of heart failure (HF) with the progressive worsening of cardiac performance due to structural and functional alterations. Therefore, we studied cardiac function in adult mice following MI using the Millar pressure-volume (P-V) conductance catheter system in vivo during the later phase of compensatory remodeling and decompensation to HF. We evaluated load-dependent and -independent parameters in control and 2-, 4-, 6-, and 10-wk post-MI mice and integrated changes in function with changes in gene expression. Our results indicated a significant deterioration of cardiac function in post-MI mice over time, reflected first by systolic dysfunction, followed by a transient improvement before further decline in both systolic and diastolic function. Associated with the function and adaptive remodeling were transient changes in fetal gene and extracellular matrix gene expression. However, undermining the compensatory remodeling response was a continual decline in cardiac contractility, which promoted the transition into failure. Our study provided a scheme of integrated cardiac function and gene expression changes occurring during the adaptive and maladaptive response of the heart independent of systemic vascular properties during the transition to HF following MI in mice. P-V loop analysis was used to quantitatively evaluate the gradual deterioration in cardiac function post-MI. P-V loop analysis was found to be an appropriate method for assessment of global cardiac function under varying load-dependent and independent conditions in the murine model with many similarities to data obtained from larger animals and humans. PMID- 17720768 TI - Exercise training normalizes beta-adrenoceptor expression in dogs susceptible to ventricular fibrillation. AB - Previous studies demonstrated an enhanced beta(2)-adrenoceptor (AR) responsiveness in animals susceptible to ventricular fibrillation (VF) that was eliminated by exercise training. The present study investigated the effects of endurance exercise training on beta(1)-AR and beta(2)-AR expression in dogs susceptible to VF. Myocardial ischemia was induced by a 2-min occlusion of the left circumflex artery during the last minute of exercise in dogs with healed infarctions: 20 had VF [susceptible (S)] and 13 did not [resistant (R)]. These dogs were randomly assigned to either 10-wk exercise training [treadmill running; n = 9 (S) or 8 (R)] or an equivalent sedentary period [n = 11 (S) or 5 (R)]. Left ventricular tissue beta-AR protein and mRNA were quantified by Western blot analysis and RT-PCR, respectively. Because beta(2)-ARs are located in caveolae, caveolin-3 was also quantified. beta(1)-AR gene expression decreased ( approximately 5-fold), beta(2)-AR gene expression was not changed, and the ratio of beta(2)-AR to beta(1)-AR gene expression was significantly increased in susceptible compared with resistant dogs. beta(1)-AR protein decreased ( approximately 50%) and beta(2)-AR protein increased (400%) in noncaveolar fractions of the cell membrane in susceptible dogs. Exercise training returned beta(1)-AR gene expression to levels seen in resistant animals but did not alter beta(2)-AR protein levels in susceptible dogs. These data suggest that beta(1)-AR gene expression was decreased in susceptible dogs compared with resistant dogs and, further, that exercise training improves beta(1)-AR gene expression, thereby restoring a more normal beta-AR balance. PMID- 17720770 TI - Cardiac proinflammatory pathways are altered with different dietary n-6 linoleic to n-3 alpha-linolenic acid ratios in normal, fat-fed pigs. AB - Although dietary fat has been associated with inflammation and cardiovascular diseases (CVD), most studies have focused on individuals with preexisting diseases. However, the role of dietary fatty acids on inflammatory pathways before the onset of any abnormality may be more relevant for identifying initiating factors and interventions for CVD prevention. We fed young male pigs one of three diets differing in n-6 and n-3 polyunsaturated fatty acids (PUFA) linoleic acid (LA, 18:2n-6) and alpha-linolenic acid (ALA, 18:3n-3) for 30 days. Cardiac membrane phospholipid fatty acids, phospholipase A(2) (PLA(2)) isoform activities, and cyclooxygenase (COX)-1 and -2 and 5-lipoxygenase (5-LO) expression were measured. The low PUFA diet (% energy, 1.2% LA+0.06% ALA) increased arachidonic acid (AA) and decreased eicosapentaenoic acid (EPA) in heart membranes and increased Ca(2+)-independent iPLA(2) activity, COX-2 expression, and activation of 5-LO. Increasing dietary ALA while keeping LA constant (1.4% LA+1.2% ALA) decreased the heart membrane AA, increased EPA, and prevented proinflammatory enzyme activation. However, regardless of high ALA, high dietary LA (11.6% LA and 1.2% ALA) decreased EPA and led to a high heart membrane AA, and Ca(2+)-dependent cPLA(2) with a marked increase in nitrosative stress. Our results suggest that the potential cardiovascular benefit of ALA is achieved only when dietary LA is reduced concomitantly rather than fed with high LA diet. The increased nitrosative stress in the unstressed heart with high dietary LA suggests that biomarkers of nitrosative stress may offer a useful early marker of the effects of dietary fat on oxidative tissue stress. PMID- 17720771 TI - ROK contribution to endothelin-mediated contraction in aorta and mesenteric arteries following intermittent hypoxia/hypercapnia in rats. AB - We reported previously that intermittent hypoxia with CO(2) to maintain eucapnia (IH-C) elevates plasma endothelin-1 (ET-1) and arterial pressure. In small mesenteric arteries (sMA; inner diameter = 150 microm), IH-C augments ET-1 constrictor sensitivity but diminishes ET-1-induced increases in intracellular Ca(2+) concentration, suggesting IH-C exposure increases both ET-1 levels and ET 1-stimulated Ca(2+) sensitization. Because Rho-associated kinase (ROK) can mediate Ca(2+) sensitization, we hypothesized that augmented vasoconstrictor sensitivity to ET-1 in arteries from IH-C-exposed rats is dependent on ROK activation. In thoracic aortic rings, ET-1 contraction was not different between groups, but ROK inhibition (Y-27632, 3 and 10 microM) attenuated ET-1 contraction more in IH-C than in sham arteries (50 +/- 11 and 78 +/- 7% vs. 41 +/- 12 and 48 +/- 9% inhibition, respectively). Therefore, ROK appears to contribute more to ET 1 contraction in IH-C than in sham aorta. In sMA, ROK inhibitors did not affect ET-1-mediated constriction in sham arteries and only modestly inhibited it in IH C arteries. In ionomycin-permeabilized sMA with intracellular Ca(2+) concentration held at basal levels, Y-27632 did not affect ET-1-mediated constriction in either IH-C or sham sMA and ET-1 did not stimulate ROK translocation. In contrast, inhibition of myosin light-chain kinase (ML-9, 100 microM) prevented ET-1-mediated constriction in sMA from both groups. Therefore, IH-C exposure increases ET-1 vasoconstrictor sensitivity in sMA but not in aorta. Furthermore, ET-1 constriction is myosin light-chain kinase dependent and mediated by Ca(2+) sensitization that is independent of ROK activation in sMA but not aorta. Thus ET-1-mediated signaling in aorta and sMA is altered by IH-C but is dependent on different second messenger systems in small vs. large arteries. PMID- 17720772 TI - PAR-2 activation at the time of reperfusion salvages myocardium via an ERK1/2 pathway in in vivo rat hearts. AB - Protease-activated receptor-2 (PAR-2) may have proinflammatory effects in some tissues and protective effects in other tissues. The role of PAR-2 in in vivo myocardial ischemia-reperfusion has not yet been determined. This study tested the hypothesis that PAR-2 activation with the PAR-2 agonist peptide SLIGRL (PAR-2 AP) reduces myocardial infarct size when given at reperfusion in vivo, and this cardioprotection involves the ERK1/2 pathway. Anesthetized rats were randomly assigned to the following groups with 30 min of regional ischemia and 3 h reperfusion: 1) control with saline; 2) vehicle (DMSO); 3) PAR-2 AP, 1 mg/kg given intravenously 5 min before reperfusion; 4) scrambled peptide (SP), 1 mg/kg; 5) the ERK1/2 inhibitor PD-98059 (PD), 0.3 mg/kg given 10 min before reperfusion; 6) the phosphatidylinositol 3-kinase inhibitor LY-294002 (LY), 0.3 mg/kg given 10 min before reperfusion; 7) PD + PAR-2 AP, 0.3 mg/kg PD given 5 min before PAR-2 AP; 8) LY + PAR-2 AP, 0.3 mg/kg LY given 5 min before PAR-2 AP; 9) chelerythrine (Chel) alone, 5 mg/kg given 10 min before reperfusion; and 10) Chel + PAR-2 AP, Chel was given 5 min before PAR-2 AP (10 min before reperfusion). Activation of ERK1/2, ERK5, Akt, and the downstream targets of ERK1/2 [P90 RSK and bcl-xl/bcl-2 associated death promoter (BAD)] was determined by Western blot analysis in separate experiments. PAR-2 AP significantly reduced infarct size compared with control (36 +/- 2% vs. 53 +/- 1%, P < 0.05), and SP had no effect on infarct size (53 +/- 3%). PAR-2 AP significantly increased phosphorylation of ERK1/2, p90RSK, and BAD but not Akt or ERK5. Accordingly, the infarct-size sparing effect of PAR 2 AP was abolished by PD (PAR-2 AP, 36 +/- 2% vs. PD + PAR-2 AP, 50 +/- 1%; P < 0.05) and by Chel (Chel + PAR-2 AP, 58 +/- 2%) but not by LY (PAR-2 AP, 36 +/- 2% vs. LY + PAR-2 AP, 38 +/- 3%; P > 0.05). Therefore, PAR-2 activation is cardioprotective in the in vivo rat heart ischemia-reperfusion model, and this protection involves the ERK1/2 pathway and PKC. PMID- 17720773 TI - beta2-Adrenergic receptor agonists stimulate L-type calcium current independent of PKA in newborn rabbit ventricular myocytes. AB - Selective stimulation of beta(2)-adrenergic receptors (ARs) in newborn rabbit ventricular myocardium invokes a positive inotropic effect that is lost during postnatal maturation. The underlying mechanisms for this age-related stimulatory response remain unresolved. We examined the effects of beta(2)-AR stimulation on L-type Ca(2+) current (I(Ca,L)) during postnatal development. I(Ca,L) was measured (37 degrees C; either Ca(2+) or Ba(2+) as the charge carrier) using the whole-cell patch-clamp technique in newborn (1 to 5 days old) and adult rabbit ventricular myocytes. Ca(2+) transients were measured concomitantly by dialyzing the cell with indo-1. Activation of beta(2)-ARs (with either 100 nM zinterol or 1 microM isoproterenol in the presence of the beta(1)-AR antagonist, CGP20712A) stimulated I(Ca,L) twofold in newborns but not in adults. The beta(2)-AR-mediated increase in Ca(2+) transient amplitude in newborns was due exclusively to the augmentation of I(Ca,L). Zinterol increased the rate of inactivation of I(Ca,L) and increased the Ca(2+) flux integral. The beta(2)-AR inverse agonist, ICI 118551 (500 nM), but not the beta(1)-AR antagonist, CGP20712A (500 nM), blocked the response to zinterol. Unexpectedly, the PKA blockers, H-89 (10 microM), PKI 6 22 amide (10 microM), and Rp-cAMP (100 microM), all failed to prevent the response to zinterol but completely blocked responses to selective beta(1)-AR stimulation of I(Ca,L) in newborns. Our results demonstrate that in addition to the conventional beta(1)-AR/cAMP/PKA pathway, newborn rabbit myocardium exhibits a novel beta(2)-AR-mediated, PKA-insensitive pathway that stimulates I(Ca,L). This striking developmental difference plays a major role in the age-related differences in inotropic responses to beta(2)-AR agonists. PMID- 17720774 TI - The energetic state within hibernating myocardium is normal during dobutamine despite inhibition of ATP-dependent potassium channel opening with glibenclamide. AB - Within hibernating myocardium, it is uncertain whether a normal energetic state is present at baseline and whether maintaining that energy state during a catecholamine challenge is dependent on ATP-dependent potassium channel opening. In this study, 16 swine underwent a thoracotomy with placement of an external constrictor on the left anterior descending coronary artery (LAD) (hibernation model). Seven additional swine underwent a sham operation. At 10 wk, the myocardial energetic state in the LAD region was assessed by (31)P-NMR spectroscopy, and the ratio of phosphocreatine to ATP (PCr/ATP) was determined at baseline, during glibenclamide treatment (0.5 mg/kg bolus with 50 microg/min iv), and during addition of dobutamine (40 microg x kg(-1) x min(-1) iv). At baseline, transmural blood flow in the LAD and remote region was 0.75 +/- 0.11 and 0.88 +/- 0.09 ml x min(-1) x g(-1), respectively (P < 0.01), in hibernating hearts and 0.83 +/- 0.12 and 0.88 +/- 0.15 ml x min(-1) x g(-1), respectively (not significant), in sham-operated hearts. Under basal conditions, PCr/ATP in the LAD region of hibernating and sham pigs was 2.15 +/- 0.04 and 2.11 +/- 0.05, respectively (not significant). In sham pigs, addition of dobutamine to glibenclamide increased the double product from 10.4 +/- 0.8 to 23.9 +/- 4.0 mmHg x beats x min(-1) x 1,000 (P < 0.05) and decreased transmural PCr/ATP from 2.06 +/- 0.06 to 1.69 +/- 0.06 (P < 0.05). Dobutamine increased the double product in hibernating pigs in a similar fashion and, despite a 40% lower blood flow response, induced an equivalent decrease in PCr/ATP from 2.04 +/- 0.04 to 1.73 +/ 0.08 (P < 0.05). In conclusion, we found that, in chronic hibernating swine myocardium with reduced basal blood flow and perfusion reserve, the transmural energetic state, defined by PCr/ATP, is normal during addition of dobutamine, despite inhibition of ATP-dependent potassium channel opening with glibenclamide. These data suggest that important adaptations other than the ATP-dependent potassium channel opening allow hibernating myocardium to operate over a lower range of the oxygen supply-demand relationship to protect against myocardial ischemia. PMID- 17720775 TI - Expression of HDAC1 and CBP/p300 in human colorectal carcinomas. AB - BACKGROUND: The histone-modifying enzymes histone deacetylase (HDAC) and histone acetyltransferase (HAT) control gene transcriptional activation and repression in human malignancies. AIMS: To analyse the expression of HDAC/HAT-associated molecules such as HDAC1, CREB-binding protein (CBP) and p300 in human colorectal carcinomas, and investigate the relationship between their expression levels and clinicopathological parameters. METHODS: Expression levels of HDAC1, CBP, and p300 in human colorectal cancer were investigated by immunohistochemistry. In situ hybridisation (ISH) and reverse transcription (RT)-PCR analyses were also carried out to confirm mRNA expression levels of these genes. Immunoreactivity was evaluated semi-quantitatively using a staining index (SI). The relationships between the SIs and clinicopathological findings were analysed and survival curves were calculated using the Kaplan-Meier method and log-rank tests. RESULTS: The mean SIs for HDAC1, CBP, and p300 in this series of tumours were much higher than those in normal colonic mucosa. The presence of HDAC1 and CBP mRNAs on colorectal carcinoma cells as well as normal epithelial cells was confirmed by ISH analysis. A marked increase in p300 mRNA levels was detected in a majority of cases by RT-PCR. Among the patients with colorectal cancer, overexpression of p300 (SI>11.9) correlated with a poor prognosis, whereas high CBP expression levels (SI>16.6) indicated long-term survival. CONCLUSION: Results showed the up regulation of these three histone-modifying molecules in this series of colorectal cancers and suggested that monitoring of CBP and p300 may assist prediction of the prognosis in patients with colorectal adenocarcinoma. PMID- 17720776 TI - Expression of androgen receptor through androgen-converting enzymes is associated with biological aggressiveness in prostate cancer. AB - AIMS: The association between the expression of androgen receptor (AR) or androgen-converting enzymes and malignant potential in prostate cancer (PCa) was examined. METHODS: PCa specimens from 44 cases of stage II, 10 cases of stage III, four cases of stage IV and two recurrent cases were semi-quantitatively studied with immunohistochemistry for AR and androgen-converting enzymes. RESULTS: The expression scores for AR, 5alpha-reductase type 1 (SRD5A1), 5alpha reductase type 2 (SRD5A2), and aldo-keto reductase family 1 member C3 (AKR1C3) in the metastatic lesion of stage IV or recurrent cancer (n = 6) were 284.2 (30.1), 300 (0.0), 279.2 (51) and 254.2 (74.9), respectively; these scores were significantly higher than the respective scores of 121.8 (82.1), 135.1 (59.7), 167.0 (66.4) and 150.5 (62.8) for stage II and III cancer (n = 54) (p<0.001, p<0.001, p = 0.002 and p = 0.018, respectively). The expression scores for AR and SRD5A1 in stage II and III cancer with Gleason score 7 (n = 19) were 128.7 (72.3) and 150.5 (52.9); these were significantly higher than the scores of 78.8 (67.2) and 100.0 (39.6), respectively, for cancers with a Gleason score of < or =6 (n = 20) (p = 0.032 and p = 0.002, respectively). The expression scores for AR, SRD5A1 and AKR1C3 in stage II and III cancer with primary Gleason pattern > or =4 (n = 21) were 158.1 (84.3), 158.3 (61.1) and 173.8 (64.8); these were significantly higher than the scores of 98.6 (72.8), 120.3 (54.7) and 135.6 (57.6), respectively, for cancers with primary Gleason pattern < or =3 (n = 33) (p = 0.011, p = 0.026 and p = 0.034, respectively). Within Gleason score 9 cancer, the expression scores for AR and SRD5A1 in the primary lesion of stage IV (n = 3) were 276.7 (5.8) and 283.3 (28.9); these scores were significantly higher than the scores of 182.1 (86.0) and 140.0 (56.6), respectively, for stage II and III cancer (n = 7) (p = 0.027 and p = 0.001, respectively). CONCLUSIONS: Both AR and androgen-converting enzymes were upregulated in high-grade or advanced PCa. PMID- 17720777 TI - Influence of food intake on the pharmacokinetics of miglustat, an inhibitor of glucosylceramide synthase. AB - The objective of this study was to investigate the effect of food on the pharmacokinetics of miglustat, an inhibitor of glucosylceramide synthase. Twenty four healthy male (n = 9) and female (n = 15) subjects were treated in a randomized, 2-way crossover design with a single oral dose of 100 mg miglustat with or without food. Consumption of a standard high-fat breakfast within 30 minutes before administration of miglustat significantly reduced peak exposure but did not significantly affect the extent of systemic exposure to miglustat. The peak plasma concentration (C(max)) decreased by 36% on average following administration with food. Area under the plasma concentration-time curve (AUC(0 infinity)) showed a modest (14%) decrease with food, but the 90% confidence interval was within the acceptance limit of 80% to 125%. The median (min-max) time to C(max) (t(max)) was prolonged from 2.5 (1.0-4.0) hours in the fasted state to 4.5 (1.5-8.0) hours in the fed state, whereas the apparent terminal half life was approximately 8 hours and not affected by food. In conclusion, the intake of food has an effect on some pharmacokinetic parameters such as C(max) and t(max) but does not affect the extent of exposure to miglustat. The observed effects of food intake on the pharmacokinetics of miglustat are not considered to be of clinical relevance. PMID- 17720778 TI - A simple screening method for detection of Klinefelter syndrome and other X chromosome aneuploidies based on copy number of the androgen receptor gene. AB - Due to the high prevalence and variable phenotype of patients with Klinefelter syndrome, there is a need for a robust and rapid screening method allowing early diagnosis. Here, we report on the development and detailed clinical validation of a quantitative real-time PCR (qPCR)-based method of the copy number assessment of the androgen receptor (AR) gene, located to Xq11.2-q12. We analysed samples from 50 individuals, including a healthy male and female controls and patients with Klinefelter syndrome (47,XXY; 48,XXXY) (n = 28), mosaicisms (46,XX/47,XXY/48XXYY; 45,X/46,XY) (n = 3), other sex chromosome abnormalities (46,XX males; 47,XYY)(n = 4) and normal karyotypes (46,XY) (n = 13). The reference range for the AR-copy number was established as 0.8-1.2 for one copy and 1.7-2.3 for two copies. The qPCR results were within the reference range in 17/18 samples (94%) or 30/31 (97%) samples with one or two copies of the AR gene, respectively. None of the Klinefelter patients were misdiagnosed as having a karyotype with only one X chromosome, and in none of the 46,XY males were two copies demonstrated. We systematically compared qPCR results with those obtained with another PCR-based method, the XIST-gene expression. The XIST-expression based assay was correct in only 29/36 samples (81%). Our findings demonstrated that the AR-qPCR technique is a simple and reliable screening method for diagnosis of patients with Klinefelter syndrome or other chromosomal disorders involving an aberrant number of X chromosomes. PMID- 17720779 TI - gerT, a newly discovered germination gene under the control of the sporulation transcription factor sigmaK in Bacillus subtilis. AB - We report the identification of a gene, herein designated gerT (formerly yozR), that is involved in germination by spores of Bacillus subtilis. The gerT gene is induced late in sporulation under the positive control of the transcription factor sigma(K) and under the negative control of the DNA-binding protein GerE. The gerT gene product (GerT) is a component of the spore coat, and its incorporation into the coat takes place in two stages. GerT initially assembles into foci, which then spread around the developing spore in a process that is dependent on the morphogenetic protein CotE. Mutant spores lacking GerT respond poorly to multiple germinants and are impaired at an early stage of germination. PMID- 17720780 TI - Inhibition of staphylococcal biofilm formation by nitrite. AB - Several environmental stresses have been demonstrated to increase polysaccharide intercellular adhesin (PIA) synthesis and biofilm formation by the human pathogens Staphylococcus aureus and Staphylococcus epidermidis. In this study we characterized an adaptive response of S. aureus SA113 to nitrite-induced stress and show that it involves concomitant impairment of PIA synthesis and biofilm formation. Transcriptional analysis provided evidence that nitrite, either as the endogenous product of respiratory nitrate reduction or after external addition, causes repression of the icaADBC gene cluster, mediated likely by IcaR. Comparative microarray analysis revealed a global change in gene expression during growth in the presence of 5 mM sodium nitrite and indicated a response to oxidative and nitrosative stress. Many nitrite-induced genes are involved in DNA repair, detoxification of reactive oxygen and nitrogen species, and iron homeostasis. Moreover, preformed biofilms could be eradicated by the addition of nitrite, likely the result of the formation of toxic acidified nitrite derivatives. Nitrite-mediated inhibition of S. aureus biofilm formation was abrogated by the addition of nitric oxide (NO) scavengers, suggesting that NO is directly or indirectly involved. Nitrite also repressed biofilm formation of S. epidermidis RP62A. PMID- 17720781 TI - Genome-wide transcriptional changes in Streptococcus gordonii in response to competence signaling peptide. AB - Streptococcus gordonii is a primary colonizer of the multispecies biofilm on tooth surfaces forming dental plaque and a potential agent of endocarditis. The recent completion of the genome sequence of the naturally competent strain Challis allowed the design of a spotted oligonucleotide microarray to examine a genome-wide response of this organism to environmental stimuli such as signal peptides. Based on temporal responses to synthetic competence signaling peptide (CSP) as indicated by transformation frequencies, the S. gordonii transcriptome was analyzed at various time points after CSP exposure. Microarray analysis identified 35 candidate early genes and 127 candidate late genes that were up regulated at 5 and 15 min, respectively; these genes were often grouped in clusters. Results supported published findings on S. gordonii competence, showing up-regulation of 12 of 16 genes that have been reported to affect transformation frequencies in this species. Comparison of CSP-induced S. gordonii transcriptomes to results published for Streptococcus pneumoniae strains identified both conserved and species-specific genes. Putative intergenic regulatory sites, such as the conserved combox sequence thought to be a binding site for competence sigma factor, were found preceding S. gordonii late responsive genes. In contrast, S. gordonii early CSP-responsive genes were not preceded by the direct repeats found in S. pneumoniae. These studies provide the first insights into a genome-wide transcriptional response of an oral commensal organism. They offer an extensive analysis of transcriptional changes that accompany competence in S. gordonii and form a basis for future intra- and interspecies comparative analyses of this ecologically important phenotype. PMID- 17720782 TI - New locus important for Myxococcus social motility and development. AB - The mts locus in salt-tolerant Myxococcus fulvus HW-1 was found to be critical for gliding motility, fruiting-body formation, and sporulation. The homologous genes in Myxococcus xanthus are also important for social motility and fruiting body development. The mts genes were determined to be involved in cell-cell cohesion in both myxobacterial species. PMID- 17720783 TI - Role of sigma factors in controlling global gene expression in light/dark transitions in the cyanobacterium Synechocystis sp. strain PCC 6803. AB - We report on differential gene expression in the cyanobacterium Synechocystis sp. strain PCC 6803 after light-dark transitions in wild-type, DeltasigB, and DeltasigD strains. We also studied the effect of day length in the presence of glucose on a DeltasigB DeltasigE mutant. Our results indicated that the absence of SigB or SigD predominately altered gene expression in the dark or in the light, respectively. In the light, approximately 350 genes displayed transcript levels in the DeltasigD strain that were different from those of the wild type, with over 200 of these up-regulated in the mutant. In the dark, removal of SigB altered more than 150 genes, and the levels of 136 of these were increased in the mutant compared to those in the wild type. The removal of both SigB and SigE had a major impact on gene expression under mixotrophic growth conditions and resulted in the inability of cells to grow in the presence of glucose with 8-h light and 16-h dark cycles. Our results indicated the importance of group II sigma factors in the global regulation of transcription in this organism and are best explained by using the sigma cycle paradigm with the stochastic release model described previously (R. A. Mooney, S. A. Darst, and R. Landick, Mol. Cell 20:335-345, 2005). We combined our results with the total protein levels of the sigma factors in the light and dark as calculated previously (S. Imamura, S. Yoshihara, S. Nakano, N. Shiozaki, A. Yamada, K. Tanaka, H. Takahashi, M. Asayama, and M. Shirai, J. Mol. Biol. 325:857-872, 2003; S. Imamura, M. Asayama, H. Takahashi, K. Tanaka, H. Takahashi, and M. Shirai, FEBS Lett. 554:357-362, 2003). Thus, we concluded that the control of global transcription is based on the amount of the various sigma factors present and able to bind RNA polymerase. PMID- 17720784 TI - A TolC-like protein is required for heterocyst development in Anabaena sp. strain PCC 7120. AB - The filamentous cyanobacterium Anabaena sp. strain PCC 7120 forms heterocysts in a semiregular pattern when it is grown on N2 as the sole nitrogen source. The transition from vegetative cells to heterocysts requires marked metabolic and morphological changes. We show that a trimeric pore-forming outer membrane beta barrel protein belonging to the TolC family, Alr2887, is up-regulated in developing heterocysts and is essential for diazotrophic growth. Mutants defective in Alr2887 did not form the specific glycolipid layer of the heterocyst cell wall, which is necessary to protect nitrogenase from external oxygen. Comparison of the glycolipid contents of wild-type and mutant cells indicated that the protein is not involved in the synthesis of glycolipids but might instead serve as an exporter for the glycolipid moieties or enzymes involved in glycolipid attachment. We propose that Alr2887, together with an ABC transporter like DevBCA, is part of a protein export system essential for assembly of the heterocyst glycolipid layer. We designate the alr2887 gene hgdD (heterocyst glycolipid deposition protein). PMID- 17720785 TI - Complex regulation of urease formation from the two promoters of the ure operon of Klebsiella pneumoniae. AB - Klebsiella pneumoniae can use urea as the sole source of nitrogen, thanks to a urease encoded by the ureDABCEFG operon. Expression of this operon is independent of urea and is regulated by the supply of nitrogen in the growth medium. When cells were growth rate limited for nitrogen, the specific activity of urease was about 70 times higher than that in cells grown under conditions of excess nitrogen. Much of this nitrogen regulation of urease formation depended on the nitrogen regulatory system acting through the nitrogen assimilation control protein, NAC. In a strain deleted for the nac gene, nitrogen limitation resulted in only a 7-fold increase in the specific activity of urease, in contrast to the 70-fold increase seen in that of the wild type. The ure operon was transcribed from two promoters. The proximal promoter (P1) had an absolute requirement for NAC; little or no transcription was seen in the absence of NAC. The distal promoter (P2) was independent of NAC, but its activity increased about threefold when the growth rate of the cells was limited by the nitrogen source. Transcriptional regulation of P1 and P2 accounted for most of the changes in urease activity seen under various nitrogen conditions. However, when transcription of ureDABCEFG was less than 20% of its maximum, the amount of active urease formed per transcript of ure decreased almost linearly with decreasing transcription. This may reflect a defect in the assembly of active urease and accounted for as much as a threefold activity difference under the conditions tested here. Thus, the ure operon was transcribed from a NAC independent promoter (P2) and the most strongly NAC-dependent promoter known (P1). Most of the regulation of urease formation was transcriptional, but when ure transcription was low, assembly of active urease also was defective. PMID- 17720786 TI - The peptidyl-prolyl isomerase activity of SlyD is not required for maturation of Escherichia coli hydrogenase. AB - Escherichia coli SlyD, which is involved in the biosynthesis of the metal cluster in the [NiFe]-hydrogenase enzymes, exhibits several activities including that of a peptidyl-prolyl isomerase (PPIase). Mutations that result in deficient PPIase activity do not produce corresponding decreases in the other activities of SlyD in vitro or in hydrogenase production levels in vivo. PMID- 17720787 TI - Pyocin S2 (Sa) kills Pseudomonas aeruginosa strains via the FpvA type I ferripyoverdine receptor. AB - Soluble (S-type) pyocins are Pseudomonas aeruginosa bacteriocins that kill nonimmune P. aeruginosa strains via a specific receptor. The genes coding for pyocin Sa (consisting of a killing protein and an immunity protein) were cloned and expressed in Escherichia coli. Sequence analysis revealed that Sa is identical to pyocin S2. Seventy-nine strains of P. aeruginosa were tested for their sensitivity to pyocins S1, S2, and S3, and their ferripyoverdine receptors were typed by multiplex PCR. No strain was found to be sensitive to both S2 and S3, suggesting that the receptors for these two pyocins cannot coexist in one strain. As expected, all S3-sensitive strains had the type II ferripyoverdine receptor fpvA gene, confirming our previous reports. S1 killed strains irrespective of the type of ferripyoverdine receptor they produced. All S2 sensitive strains had the type I fpvA gene, and the inactivation of type I fpvA in an S2-sensitive strain conferred resistance to the S2 pyocin. Accordingly, complementation with type I fpvA in trans restored sensitivity to S2. Some S2 resistant type I fpvA-positive strains were detected, the majority (all but five) of which had the S1-S2 immunity gene. Comparison of type I fpvA sequences from immunity gene-negative S2-sensitive and S2-resistant strains revealed only a valine-to-isoleucine substitution at position 46 of type I FpvA. However, both type I fpvA genes conferred the capacity for type I pyoverdine utilization and sensitivity to S2. When these two type I fpvA genes were introduced into strain 7NSK2 carrying mutations in type II fpvA (encoding the type II pyoverdine receptor) and fpvB (encoding the alternative type I receptor), growth in the presence of type I pyoverdine was observed and the strain became sensitive to S2. We also found that type I pyoverdine could signal type II pyoverdine production via the type I FpvA receptor in 7NSK2. PMID- 17720788 TI - Activation of yeaR-yoaG operon transcription by the nitrate-responsive regulator NarL is independent of oxygen- responsive regulator Fnr in Escherichia coli K-12. AB - The facultative aerobe Escherichia coli K-12 can use respiratory nitrate ammonification to generate energy during anaerobic growth. The toxic compound nitric oxide is a by-product of this metabolism. Previous transcript microarray studies identified the yeaR-yoaG operon, encoding proteins of unknown function, among genes whose transcription is induced in response to nitrate, nitrite, or nitric oxide. Nitrate and nitrite regulate anaerobic respiratory gene expression through the NarX-NarL and NarQ-NarP two-component systems. All known Nar activated genes also require the oxygen-responsive Fnr transcription activator. However, previous studies indicated that yeaR-yoaG operon transcription does not require Fnr activation. Here, we report results from mutational analyses demonstrating that yeaR-yoaG operon transcription is activated by phospho-NarL protein independent of the Fnr protein. The phospho-NarL protein binding site is centered at position -43.5 with respect to the transcription initiation site. Expression from the Shewanella oneidensis MR-1 nnrS gene promoter, cloned into E. coli, similarly was activated by phospho-NarL protein independent of the Fnr protein. Recently, yeaR-yoaG operon transcription was shown to be regulated by the nitric oxide-responsive NsrR repressor (N. Filenko et al., J. Bacteriol. 189:4410-4417, 2007). Our mutational analyses reveal the individual contributions of the Nar and NsrR regulators to overall yeaR-yoaG operon expression and document the NsrR operator centered at position -32. Thus, control of yeaR-yoaG operon transcription provides an example of overlapping regulation by nitrate and nitrite, acting through the Nar regulatory system, and nitric oxide, acting through the NsrR repressor. PMID- 17720789 TI - Involvement of the detoxifying enzyme lactoylglutathione lyase in Streptococcus mutans aciduricity. AB - Streptococcus mutans, a normal inhabitant of dental plaque, is considered a primary etiological agent of dental caries. Its main virulence factors are acidogenicity and aciduricity, the abilities to produce acid and to survive and grow at low pH, respectively. Metabolic processes are finely regulated following acid exposure in S. mutans. Proteome analysis of S. mutans demonstrated that lactoylglutathione lyase (LGL) was up-regulated during acid challenge. The LGL enzyme catalyzes the conversion of toxic methylglyoxal, derived from glycolysis, to S-D-lactoylglutathione. Methylglyoxal inhibits the growth of cells in all types of organisms. The current study aimed to investigate the relationship between LGL and aciduricity and acidogenicity in S. mutans. An S. mutans isogenic mutant defective in lgl (LGLKO) was created, and its growth kinetics were characterized. Insertional inactivation of lgl resulted in an acid-sensitive phenotype. However, the glycolytic rate at pH 5.0 was greater for LGLKO than for S. mutans UA159 wild-type cells. LGL was involved in the detoxification of methylglyoxal, illustrated by the absence of enzyme activity in LGLKO and the hypersensitivity of LGLKO to methylglyoxal, compared with UA159 (MIC of 3.9 and 15.6 mM, respectively). Transcriptional analysis of lgl conducted by quantitative real-time PCR revealed that lgl was up-regulated (approximately sevenfold) during the exponential growth phase compared with that in the stationary growth phase. Gene expression studies conducted at low pH demonstrated that lgl was induced during acidic growth (approximately 3.5-fold) and following acid adaptation (approximately 2-fold). This study demonstrates that in S. mutans, LGL functions in the detoxification of methylglyoxal, resulting in increased aciduricity. PMID- 17720790 TI - Cobalt targets multiple metabolic processes in Salmonella enterica. AB - Cobalt is essential for growth of Salmonella enterica and other organisms, yet this metal can be toxic when present in excess. Wild-type Salmonella exhibits several metabolic defects when grown in the presence of cobalt, some of which generate visible growth consequences. Work herein identifies sulfur assimilation, iron homeostasis, and Fe-S cluster metabolism as targets for cobalt toxicity. In each case it is proposed that cobalt exerts its effect by one of two mechanisms: direct competition with iron or indirectly through a mechanism that involves the status of reduced thiols in the cell. Cobalt toxicity results in decreased siroheme production, increased expression of the Fur regulon, and decreased activity of Fe-S cluster proteins. The consequences of reduced sulfite reductase activity in particular are exacerbated by the need for glutathione in cobalt resistance. Significantly, independent metabolic perturbations could be detected at cobalt concentrations below those required to generate a detectable growth defect. PMID- 17720792 TI - Cloning of a gene cluster involved in the catabolism of p-nitrophenol by Arthrobacter sp. strain JS443 and characterization of the p-nitrophenol monooxygenase. AB - The npd gene cluster, which encodes the enzymes of a p-nitrophenol catabolic pathway from Arthrobacter sp. strain JS443, was cloned and sequenced. Three genes, npdB, npdA1, and npdA2, were independently expressed in Escherichia coli in order to confirm the identities of their gene products. NpdA2 is a p nitrophenol monooxygenase belonging to the two-component flavin-diffusible monooxygenase family of reduced flavin-dependent monooxygenases. NpdA1 is an NADH dependent flavin reductase, and NpdB is a hydroxyquinol 1,2-dioxygenase. The npd gene cluster also includes a putative maleylacetate reductase gene, npdC. In an in vitro assay containing NpdA2, an E. coli lysate transforms p-nitrophenol stoichiometrically to hydroquinone and hydroxyquinol. It was concluded that the p nitrophenol catabolic pathway in JS443 most likely begins with a two-step transformation of p-nitrophenol to hydroxy-1,4-benzoquinone, catalyzed by NpdA2. Hydroxy-1,4-benzoquinone is reduced to hydroxyquinol, which is degraded through the hydroxyquinol ortho cleavage pathway. The hydroquinone detected in vitro is a dead-end product most likely resulting from chemical or enzymatic reduction of the hypothetical intermediate 1,4-benzoquinone. NpdA2 hydroxylates a broad range of chloro- and nitro-substituted phenols, resorcinols, and catechols. Only p nitro- or p-chloro-substituted phenols are hydroxylated twice. Other substrates are hydroxylated once, always at a position para to a hydroxyl group. PMID- 17720791 TI - Epsilon-toxin plasmids of Clostridium perfringens type D are conjugative. AB - Isolates of Clostridium perfringens type D produce the potent epsilon-toxin (a CDC/U.S. Department of Agriculture overlap class B select agent) and are responsible for several economically significant enterotoxemias of domestic livestock. It is well established that the epsilon-toxin structural gene, etx, occurs on large plasmids. We show here that at least two of these plasmids are conjugative. The etx gene on these plasmids was insertionally inactivated using a chloramphenicol resistance cassette to phenotypically tag the plasmid. High frequency conjugative transfer of the tagged plasmids into the C. perfringens type A strain JIR325 was demonstrated, and the resultant transconjugants were shown to act as donors in subsequent mating experiments. We also demonstrated the transfer of "unmarked" native epsilon-toxin plasmids into strain JIR325 by exploiting the high transfer frequency. The transconjugants isolated in these experiments expressed functional epsilon-toxin since their supernatants had cytopathic effects on MDCK cells and were toxic in mice. Using the widely accepted multiplex PCR approach for toxin genotyping, these type A-derived transconjugants were genotypically type D. These findings have significant implications for the C. perfringens typing system since it is based on the toxin profile of each strain. Our study demonstrated the fluid nature of the toxinotypes and their dependence upon the presence or absence of toxin plasmids, some of which have for the first time been shown to be conjugative. PMID- 17720793 TI - Abh and AbrB control of Bacillus subtilis antimicrobial gene expression. AB - The Bacillus subtilis abh gene encodes a protein whose N-terminal domain has 74% identity to the DNA-binding domain of the global regulatory protein AbrB. Strains with a mutation in abh showed alterations in the production of antimicrobial compounds directed against some other Bacillus species and gram-positive microbes. Relative to its wild-type parental strain, the abh mutant was found deficient, enhanced, or unaffected for the production of antimicrobial activity. Using lacZ fusions, we examined the effects of abh upon the expression of 10 promoters known to be regulated by AbrB, including five that transcribe well characterized antimicrobial functions (SdpC, SkfA, TasA, sublancin, and subtilosin). For an otherwise wild-type background, the results show that Abh plays a negative regulatory role in the expression of four of the promoters, a positive role for the expression of three, and no apparent regulatory role in the expression of the other three promoters. Binding of AbrB and Abh to the promoter regions was examined using DNase I footprinting, and the results revealed significant differences. The transcription of abh is not autoregulated, but it is subject to a degree of AbrB-afforded negative regulation. The results indicate that Abh is part of the complex interconnected regulatory system that controls gene expression during the transition from active growth to stationary phase. PMID- 17720794 TI - Corynebacterium diphtheriae: identification and characterization of a channel forming protein in the cell wall. AB - The cell wall fraction of the gram-positive, nontoxic Corynebacterium diphtheriae strain C8r(-) Tox- (=ATCC 11913) contained a channel-forming protein, as judged from reconstitution experiments with artificial lipid bilayer experiments. The channel-forming protein was present in detergent-treated cell walls and in extracts of whole cells obtained using organic solvents. The protein had an apparent molecular mass of about 66 kDa as determined on Tricine-containing sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels and consisted of subunits having a molecular mass of about 5 kDa. Single-channel experiments with the purified protein suggested that the protein formed channels with a single channel conductance of 2.25 nS in 1 M KCl. Further single-channel analysis suggested that the cell wall channel is wide and water filled because it has only slight selectivity for cations over anions and its conductance followed the mobility sequence of cations and anions in the aqueous phase. Antibodies raised against PorA, the subunit of the cell wall channel of Corynebacterium glutamicum, detected both monomers and oligomers of the isolated protein, suggesting that there are highly conserved epitopes in the cell wall channels of C. diphtheriae and PorA. Localization of the protein on the cell surface was confirmed by an enzyme-linked immunosorbent assay. The prospective homology of PorA with the cell wall channel of C. diphtheriae was used to identify the cell wall channel gene, cdporA, in the known genome of C. diphtheriae. The gene and its flanking regions were cloned and sequenced. CdporA is a protein that is 43 amino acids long and does not have a leader sequence. cdporA was expressed in a C. glutamicum strain that lacked the major outer membrane channels PorA and PorH. Organic solvent extracts of the transformed cells formed in lipid bilayer membranes the same channels as the purified CdporA protein of C. diphtheriae formed, suggesting that the expressed protein is able to complement the PorA and PorH deficiency of the C. glutamicum strain. The study is the first report of a cell wall channel in a pathogenic Corynebacterium strain. PMID- 17720795 TI - TcpA, an FtsK/SpoIIIE homolog, is essential for transfer of the conjugative plasmid pCW3 in Clostridium perfringens. AB - The conjugative tetracycline resistance plasmid pCW3 is the paradigm conjugative plasmid in the anaerobic gram-positive pathogen Clostridium perfringens. Two closely related FtsK/SpoIIIE homologs, TcpA and TcpB, are encoded on pCW3, which is significant since FtsK domains are found in coupling proteins of gram-negative conjugation systems. To develop an understanding of the mechanism of conjugative transfer in C. perfringens, we determined the role of these proteins in the conjugation process. Mutation and complementation analysis was used to show that the tcpA gene was essential for the conjugative transfer of pCW3 and that the tcpB gene was not required for transfer. Furthermore, complementation of a pCW3DeltatcpA mutant with divergent tcpA homologs provided experimental evidence that all of the known conjugative plasmids from C. perfringens use a similar transfer mechanism. Functional genetic analysis of the TcpA protein established the essential role in conjugative transfer of its Walker A and Walker B ATP binding motifs and its FtsK-like RAAG motif. It is postulated that TcpA is the essential DNA translocase or coupling protein encoded by pCW3 and as such represents a key component of the unique conjugation process in C. perfringens. PMID- 17720796 TI - Identification and characterization of TriABC-OpmH, a triclosan efflux pump of Pseudomonas aeruginosa requiring two membrane fusion proteins. AB - Pseudomonas aeruginosa achieves high-level (MIC>1 mg/ml) triclosan resistance either by constitutive expression of MexAB-OprM, an efflux pump of the resistance nodulation cell division (RND) family, or expression of MexCD-OprJ, MexEF-OprN, and MexJK-OpmH in regulatory mutants. A triclosan-resistant target enzyme and perhaps other mechanisms probably act synergistically with efflux. To probe this notion, we exposed the susceptible Delta(mexAB-oprM) Delta(mexCD-oprJ) Delta(mexEF-oprN) Delta(mexJK) Delta(mexXY) strain PAO509 to increasing triclosan concentrations and derived a resistant strain, PAO509.5. This mutant overexpressed the PA0156-PA0157-PA0158 pump, which only effluxed triclosan, but not closely related compounds, antibiotics, and divalent cations, and was therefore renamed TriABC. Constitutive expression of the triABC operon was due to a single promoter-up mutation. Deletion of two adjacent genes, pcaR and PA0159, encoding transcriptional regulators had no effect on expression of this operon. TriABC is the only P. aeruginosa RND pump which contains two membrane fusion proteins, TriA and TriB, and both are required for efflux pump function. Probably owing to tight transcriptional coupling of the triABC genes, complementation of individual mutations was only partially achievable. Full complementation was only observed when a complete triABC operon was provided in trans, either in single or multiple copies. TriABC associated with OpmH, but not OprM, for assembly of a functional triclosan efflux pump. TriABC is the fifth RND pump in P. aeruginosa shown to efficiently efflux triclosan, supporting the notion that efflux is the primary mechanism responsible for this bacterium's high intrinsic and acquired triclosan resistance. PMID- 17720797 TI - Isolated poly(3-hydroxybutyrate) (PHB) granules are complex bacterial organelles catalyzing formation of PHB from acetyl coenzyme A (CoA) and degradation of PHB to acetyl-CoA. AB - Poly(3-hydroxybutyrate) (PHB) granules isolated in native form (nPHB granules) from Ralstonia eutropha catalyzed formation of PHB from (14)C-labeled acetyl coenzyme A (CoA) in the presence of NADPH and concomitantly released CoA, revealing that PHB biosynthetic proteins (acetoacetyl-CoA thiolase, acetoacetyl CoA reductase, and PHB synthase) are present and active in isolated nPHB granules in vitro. nPHB granules also catalyzed thiolytic cleavage of PHB in the presence of added CoA, resulting in synthesis of 3-hydroxybutyryl-CoA (3HB-CoA) from PHB. Synthesis of 3HB-CoA was also shown by incubation of artificial (protein-free) PHB with CoA and PhaZa1, confirming that PhaZa1 is a PHB depolymerase catalyzing the thiolysis reaction. Acetyl-CoA was the major product detectable after incubation of nPHB granules in the presence of NAD(+), indicating that downstream mobilizing enzyme activities were also present and active in isolated nPHB granules. We propose that intracellular concentrations of key metabolites (CoA, acetyl-CoA, 3HB-CoA, NAD(+)/NADH) determine whether a cell accumulates or degrades PHB. Since the degradation product of PHB is 3HB-CoA, the cells do not waste energy by synthesis and degradation of PHB. Thus, our results explain the frequent finding of simultaneous synthesis and breakdown of PHB. PMID- 17720798 TI - Physical examination tests of the shoulder: a systematic review with meta analysis of individual tests. AB - OBJECTIVE: To compile and critique research on the diagnostic accuracy of individual orthopaedic physical examination tests in a manner that would allow clinicians to judge whether these tests are valuable to their practice. METHODS: A computer-assisted literature search of MEDLINE, CINAHL, and SPORTDiscus databases (1966 to October 2006) using keywords related to diagnostic accuracy of physical examination tests of the shoulder. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool was used to critique the quality of each paper. Meta-analysis through meta-regression of the diagnostic odds ratio (DOR) was performed on the Neer test for impingement, the Hawkins-Kennedy test for impingement, and the Speed test for superior labral pathology. RESULTS: Forty five studies were critiqued with only half demonstrating acceptable high quality and only two having adequate sample size. For impingement, the meta-analysis revealed that the pooled sensitivity and specificity for the Neer test was 79% and 53%, respectively, and for the Hawkins-Kennedy test was 79% and 59%, respectively. For superior labral (SLAP) tears, the summary sensitivity and specificity of the Speed test was 32% and 61%, respectively. Regarding orthopaedic special tests (OSTs) where meta-analysis was not possible either due to lack of sufficient studies or heterogeneity between studies, the list that demonstrates both high sensitivity and high specificity is short: hornblowers's sign and the external rotation lag sign for tears of the rotator cuff, biceps load II for superior labral anterior to posterior (SLAP) lesions, and apprehension, relocation and anterior release for anterior instability. Even these tests have been under-studied or are from lower quality studies or both. No tests for impingement or acromioclavicular (AC) joint pathology demonstrated significant diagnostic accuracy. CONCLUSION: Based on pooled data, the diagnostic accuracy of the Neer test for impingement, the Hawkins-Kennedy test for impingement and the Speed test for labral pathology is limited. There is a great need for large, prospective, well-designed studies that examine the diagnostic accuracy of the numerous physical examination tests of the shoulder. Currently, almost without exception, there is a lack of clarity with regard to whether common OSTs used in clinical examination are useful in differentially diagnosing pathologies of the shoulder. PMID- 17720799 TI - Post-mortem evidence of idiopathic left ventricular hypertrophy and idiopathic interstitial myocardial fibrosis: is exercise the cause? AB - A growing body of evidence reporting altered cardiac function and myocardial damage after arduous exercise, together with the increased prevalence of arrhythmias observed in highly trained athletes, suggests that repetitive bouts of prolonged, arduous exercise may be deleterious to long-term cardiac health. We report the case of an experienced, highly trained marathon runner who died suddenly while running. On post-mortem examination, left ventricle hypertrophy and idiopathic interstitial myocardial fibrosis was found. We believe that life long, repetitive bouts of arduous physical activity resulted in fibrous replacement of the myocardium, causing a pathological substrate for the propagation of fatal arrhythmias. PMID- 17720800 TI - Measles virus P protein suppresses Toll-like receptor signal through up regulation of ubiquitin-modifying enzyme A20. AB - We recently reported that the activation of NF-kappaB and AP-1 was suppressed in monocytes infected with measles virus, but not in infected epithelial cells. This cell-type-specific suppression of the inflammatory response represents a potential for measles virus to evade host immune system. In the current study, we examined the suppression mechanism of lipopolysaccharide (LPS)-induced, namely Toll-like receptor 4 (TLR4)-mediated, activation of NF-kappaB and AP-1 in measles virus-infected monocytic cells. In the infected cells, LPS treatment failed to induce the formation of active protein kinase complex containing TAK1, TAB2 and tumor necrosis factor receptor-associated factor 6 (TRAF6), dissociate from TLR complexes containing Interleukin-1 receptor-associated kinase 1 (IRAK1). Ubiquitin-modifying enzyme A20, which is a host negative feedback regulator of NF kappaB, was dramatically up-regulated in infected monocytic cells, but not in infected epithelial cells. Suppression of A20 expression by siRNA restored LPS induced signaling in infected cells. Measles virus phosphoprotein (P protein) expression was necessary and sufficient for the induction of A20. P protein interacted indirectly with a negative regulatory motif in the A20 gene promoter, and released the suppression of A20 transcription, independent of the activation of NF-kappaB. PMID- 17720801 TI - Biochemical and functional evidence for the control of pain mechanisms by dehydroepiandrosterone endogenously synthesized in the spinal cord. AB - We investigated the role and mechanism of action of dehydroepiandrosterone (DHEA) produced by the spinal cord (SC) in pain modulation in sciatic-neuropathic and control rats. Real-time polymerase chain reaction (PCR) after reverse transcription revealed cytochrome P450c17 (DHEA-synthesizing enzyme) gene repression in neuropathic rat SC. A combination of pulse-chase experiments, high performance liquid chromatography (HPLC), and flow-scintillation detection showed decreased DHEA biosynthesis from pregnenolone in neuropathic SC slices. Radioimmunoassays demonstrated endogenous DHEA level drop in neuropathic SC. Behavioral analysis showed a rapid pronociceptive and a delayed antinociceptive action of acute DHEA treatment. Inhibition of DHEA biosynthesis in the SC by intrathecally administered ketoconazole (P450c17 inhibitor) induced analgesia in neuropathic rats. BD1047 (sigma-1 receptor antagonist) blocked the transient pronociceptive effect evoked by acute DHEA administration. Chronic DHEA treatment increased and maintained elevated the basal nociceptive thresholds in neuropathic and control rats, suggesting that androgenic metabolites generated from daily administered DHEA exerted analgesic effects while DHEA itself (before being metabolized) induced a rapid pronociceptive action. Indeed, intrathecal administration of testosterone, an androgen deriving from DHEA, caused analgesia in neuropathic rats. Together, these molecular, biochemical, and functional results demonstrate that DHEA synthesized in the SC controls pain mechanisms. Possibilities are opened for pain modulation by drugs regulating P450c17 in nerve cells. PMID- 17720802 TI - Amyloid beta oligomers induce impairment of neuronal insulin receptors. AB - Recent studies have indicated an association between Alzheimer's disease (AD) and central nervous system (CNS) insulin resistance. However, the cellular mechanisms underlying the link between these two pathologies have not been elucidated. Here we show that signal transduction by neuronal insulin receptors (IR) is strikingly sensitive to disruption by soluble Abeta oligomers (also known as ADDLs). ADDLs are known to accumulate in AD brain and have recently been implicated as primary candidates for initiating deterioration of synapse function, composition, and structure. Using mature cultures of hippocampal neurons, a preferred model for studies of synaptic cell biology, we found that ADDLs caused a rapid and substantial loss of neuronal surface IRs specifically on dendrites bound by ADDLs. Removal of dendritic IRs was associated with increased receptor immunoreactivity in the cell body, indicating redistribution of the receptors. The neuronal response to insulin, measured by evoked IR tyrosine autophosphorylation, was greatly inhibited by ADDLs. Inhibition also was seen with added glutamate or potassium-induced depolarization. The effects on IR function were completely blocked by NMDA receptor antagonists, tetrodotoxin, and calcium chelator BAPTA-AM. Downstream from the IR, ADDLs induced a phosphorylation of Akt at serine473, a modification associated with neurodegenerative and insulin resistance diseases. These results identify novel factors that affect neuronal IR signaling and suggest that insulin resistance in AD brain is a response to ADDLs, which disrupt insulin signaling and may cause a brain-specific form of diabetes as part of an overall pathogenic impact on CNS synapses. PMID- 17720803 TI - The nine lives of Daniel E. Koshland, Jr. (1920-2007). PMID- 17720806 TI - Time variability in Cenozoic reconstructions of mantle heat flow: plate tectonic cycles and implications for Earth's thermal evolution. AB - The thermal evolution of Earth is governed by the rate of secular cooling and the amount of radiogenic heating. If mantle heat sources are known, surface heat flow at different times may be used to deduce the efficiency of convective cooling and ultimately the temporal character of plate tectonics. We estimate global heat flow from 65 Ma to the present using seafloor age reconstructions and a modified half-space cooling model, and we find that heat flow has decreased by approximately 0.15% every million years during the Cenozoic. By examining geometric trends in plate reconstructions since 120 Ma, we show that the reduction in heat flow is due to a decrease in the area of ridge-proximal oceanic crust. Even accounting for uncertainties in plate reconstructions, the rate of heat flow decrease is an order of magnitude faster than estimates based on smooth, parameterized cooling models. This implies that heat flow experiences short-term fluctuations associated with plate tectonic cyclicity. Continental separation does not appear to directly control convective wavelengths, but rather indirectly affects how oceanic plate systems adjust to accommodate global heat transport. Given that today's heat flow may be unusually low, secular cooling rates estimated from present-day values will tend to underestimate the average cooling rate. Thus, a mechanism that causes less efficient tectonic heat transport at higher temperatures may be required to prevent an unreasonably hot mantle in the recent past. PMID- 17720804 TI - Identification of membrane proteins by tandem mass spectrometry of protein ions. AB - The most common way of identifying proteins in proteomic analyses is to use short segments of sequence ("tags") determined by mass spectrometric analysis of proteolytic fragments. The approach is effective with globular proteins and with membrane proteins with significant polar segments between membrane-spanning alpha helices, but it is ineffective with other hydrophobic proteins where protease cleavage sites are either infrequent or absent. By developing methods to purify hydrophobic proteins in organic solvents and by fragmenting ions of these proteins by collision induced dissociation with argon, we have shown that partial sequences of many membrane proteins can be deduced easily by manual inspection. The spectra from small proteolipids (1-4 transmembrane alpha-helices) are dominated usually by fragment ions arising from internal amide cleavages, from which internal sequences can be obtained, whereas the spectra from larger membrane proteins (5-18 transmembrane alpha-helices) often contain fragment ions from N- and/or C-terminal parts yielding sequences in those regions. With these techniques, we have, for example, identified an abundant protein of unknown function from inner membranes of mitochondria that to our knowledge has escaped detection in proteomic studies, and we have produced sequences from 10 of 13 proteins encoded in mitochondrial DNA. They include the ND6 subunit of complex I, the last of its 45 subunits to be analyzed. The procedures have the potential to be developed further, for example by using newly introduced methods for protein ion dissociation to induce fragmentation of internal regions of large membrane proteins, which may remain partially folded in the gas phase. PMID- 17720805 TI - Sonic hedgehog-induced type 3 deiodinase blocks thyroid hormone action enhancing proliferation of normal and malignant keratinocytes. AB - The Sonic hedgehog (Shh) pathway plays a critical role in hair follicle physiology and is constitutively active in basal cell carcinomas (BCCs), the most common human malignancy. Type 3 iodothyronine deiodinase (D3), the thyroid hormone-inactivating enzyme, is frequently expressed in proliferating and neoplastic cells, but its role in this context is unknown. Here we show that Shh, through Gli2, directly induces D3 in proliferating keratinocytes and in mouse and human BCCs. We demonstrate that Gli-induced D3 reduces intracellular active thyroid hormone, thus resulting in increased cyclin D1 and keratinocyte proliferation. D3 knockdown caused a 5-fold reduction in the growth of BCC xenografts in nude mice. Shh-induced thyroid hormone degradation via D3 synergizes with the Shh-mediated reduction of the type 2 deiodinase, the thyroxine-activating enzyme, and both effects are reversed by cAMP. This previously unrecognized functional cross-talk between Shh/Gli2 and thyroid hormone in keratinocytes is a pathway by which Shh produces its proliferative effects and offers a potential therapeutic approach to BCC. PMID- 17720807 TI - Evidence for a diffusion-controlled mechanism for fluorescence blinking of colloidal quantum dots. AB - Fluorescence blinking in nanocrystal quantum dots is known to exhibit power-law dynamics, and several different mechanisms have been proposed to explain this behavior. We have extended the measurement of quantum-dot blinking by characterizing fluctuations in the fluorescence of single dots over time scales from microseconds to seconds. The power spectral density of these fluctuations indicates a change in the power-law statistics that occurs at a time scale of several milliseconds, providing an important constraint on possible mechanisms for the blinking. In particular, the observations are consistent with the predictions of models wherein blinking is controlled by diffusion of the energies of electron or hole trap states. PMID- 17720808 TI - Negative feedback regulation of Rac in leukocytes from mice expressing a constitutively active phosphatidylinositol 3-kinase gamma. AB - Polarization of chemotaxing cells depends on positive feedback loops that amplify shallow gradients of chemoattractants into sharp intracellular responses. In particular, reciprocal activation of phosphatidylinositol 3-kinases (PI3Ks) and small GTPases like Rac leads to accumulation, at the leading edge, of the PI3K product phosphatidylinositol 3,4,5-trisphosphate (PIP3). Mice carrying a "knockin" allele of the G protein-coupled receptor (GPCR)-activated PI3Kgamma, encoding a plasma membrane-targeted protein appeared normal, but their leukocytes showed GPCR-uncoupled PIP3 accumulation. In vivo, the mutation increased proliferation and decreased apoptosis, leading to leukocytosis and delayed resolution of inflammation in wound healing. Mutant leukocytes showed significantly impaired directional cell migration in response to chemoattractants. Stimulated mutant macrophages did not polarize PIP3 and showed a shortened Rac activation because of enhanced PI3K-dependent activation of RacGAPs. Together with the finding that chemoattractants stimulate a PIP3 dependent GAP activation in wild-type macrophages, these results identify a molecular mechanism involving PI3K- and RacGAP-dependent negative control of Rac that limits and fine-tunes feedback loops promoting cell polarization and directional motility. PMID- 17720809 TI - Large-scale, saturating insertional mutagenesis of the mouse genome. AB - We describe the construction of a large-scale, orderly assembly of mutant ES cells, generated with retroviral insertions and having mutational coverage in >90% of mouse genes. We also describe a method for isolating ES cell clones with mutations in specific genes of interest from this library. This approach, which combines saturating random mutagenesis with targeted selection of mutations in the genes of interest, was successfully applied to the gene families of G protein coupled receptors (GPCRs) and nuclear receptors. Mutant mouse strains in 60 different GPCRs were generated. Applicability of the technique for the GPCR genes, which on average represent fairly small targets for insertional mutagenesis, indicates the general utility of our approach for the rest of the genome. The method also allows for increased scale and automation for the large scale production of mutant mice, which could substantially expedite the functional characterization of the mouse genome. PMID- 17720810 TI - Structural insights into activation of phosphatidylinositol 4-kinase (Pik1) by yeast frequenin (Frq1). AB - Yeast frequenin (Frq1), a small N-myristoylated EF-hand protein, activates phosphatidylinositol 4-kinase Pik1. The NMR structure of Ca2+-bound Frq1 complexed to an N-terminal Pik1 fragment (residues 121-174) was determined. The Frq1 main chain is similar to that in free Frq1 and related proteins in the same branch of the calmodulin superfamily. The myristoyl group and first eight residues of Frq1 are solvent-exposed, and Ca2+ binds the second, third, and fourth EF-hands, which associate to create a groove with two pockets. The Pik1 peptide forms two helices (125-135 and 156-169) connected by a 20-residue loop. Side chains in the Pik1 N-terminal helix (Val-127, Ala-128, Val-131, Leu-132, and Leu-135) interact with solvent-exposed residues in the Frq1 C-terminal pocket (Leu-101, Trp-103, Val-125, Leu-138, Ile-152, and Leu-155); side chains in the Pik1 C-terminal helix (Ala-157, Ala-159, Leu-160, Val-161, Met-165, and Met-167) contact solvent-exposed residues in the Frq1 N-terminal pocket (Trp-30, Phe-34, Phe-48, Ile-51, Tyr-52, Phe-55, Phe-85, and Leu-89). This defined complex confirms that residues in Pik1 pinpointed as necessary for Frq1 binding by site directed mutagenesis are indeed sufficient for binding. Removal of the Pik1 N terminal region (residues 8-760) from its catalytic domain (residues 792-1066) abolishes lipid kinase activity, inconsistent with Frq1 binding simply relieving an autoinhibitory constraint. Deletion of the lipid kinase unique motif (residues 35-110) also eliminates Pik1 activity. In the complex, binding of Ca2+-bound Frq1 forces the Pik1 chain into a U-turn. Frq1 may activate Pik1 by facilitating membrane targeting via the exposed N-myristoyl group and by imposing a structural transition that promotes association of the lipid kinase unique motif with the kinase domain. PMID- 17720811 TI - Noncanonical Wnt-4 signaling enhances bone regeneration of mesenchymal stem cells in craniofacial defects through activation of p38 MAPK. AB - Mesenchymal stem cells (MSCs) are multipotent cells that can be differentiated into osteoblasts and provide an excellent cell source for bone regeneration and repair. Recently, the canonical Wnt/beta-catenin signaling pathway has been found to play a critical role in skeletal development and osteogenesis, implying that Wnts can be utilized to improve de novo bone formation mediated by MSCs. However, it is unknown whether noncanonical Wnt signaling regulates osteogenic differentiation. Here, we find that Wnt-4 enhanced in vitro osteogenic differentiation of MSCs isolated from human adult craniofacial tissues and promoted bone formation in vivo. Whereas Wnt-4 did not stabilize beta-catenin, it activated p38 MAPK in a novel noncanonical signaling pathway. The activation of p38 was dependent on Axin and was required for the enhancement of MSC differentiation by Wnt-4. Moreover, using two different models of craniofacial bone injury, we found that MSCs genetically engineered to express Wnt-4 enhanced osteogenesis and improved the repair of craniofacial defects in vivo. Taken together, our results reveal that noncanonical Wnt signaling could also play a role in osteogenic differentiation. Wnt-4 may have a potential use in improving bone regeneration and repair of craniofacial defects. PMID- 17720812 TI - Molecular mechanism of oxidative stress perception by the Orp1 protein. AB - In this study we investigated the molecular mechanism by which the Orp1 (Gpx3) protein in Saccharomyces cerevisiae senses and reacts with hydrogen peroxide. Upon exposure to H(2)O(2) Orp1(Cys36) forms a disulfide-bonded complex with the C terminal domain of the Yap1 protein (Yap1-cCRD). We used 4-nitrobenzo-2-oxa-1,3 diazole to identify a cysteine sulfenic acid (Cys-SOH) modification that forms on Cys(36) of Orp1(Cys36) upon exposure to H(2)O(2). Under similar conditions, neither Cys(82) of Orp1(Cys82) nor Cys(598) of Yap1 forms Cys-SOH. A homology based molecular model of Orp1 suggests that the structure of the active site of Orp1 is similar to that found in mammalian selenocysteine glutathione peroxidases. Proposed active site residues Gln(70) and Trp(125) form a catalytic triad with Cys(36) in the Orp1 molecular model. The remainder of the active site pocket is formed by Phe(38), Asn(126), and Phe(127), which are evolutionarily conserved residues. We made Q70A and W125A mutants and tested the ability of these mutants to form Cys-SOH in response to H(2)O(2). Both mutants were unable to form Cys-SOH and did not form a H(2)O(2)-inducible disulfide-bonded complex with Yap1-cCRD. The pK(a) of Cys(36) was determined to be 5.1, which is 3.2 pH units lower than that of a free cysteine (8.3). In contrast, Orp1 Cys(82) (the resolving cysteine) has a pK(a) value of 8.3. The pK(a) of Cys(36) in the Q70A and W125A mutants is also 8.3, demonstrating the importance of these residues in modulating the nucleophilic character of Cys(36). Finally, we show that S. cerevisiae strains with ORP1 Q70A and W125A mutations are less tolerant to H(2)O(2) than those containing wild-type ORP1. The results of our study suggest that attempts to identify novel redox-regulated proteins and signal transduction pathways should focus on characterization of low pK(a) cysteines. PMID- 17720813 TI - NOS2 regulation of NF-kappaB by S-nitrosylation of p65. AB - Signal transduction in the NF-kappaB transcription factor pathway is inhibited by inducible nitric oxide synthase (NOS2) activity, although the molecular mechanism(s) are incompletely understood. We have previously shown that nitric oxide (NO), derived from NOS2 consequent upon cytokine stimulation, attenuates NF kappaB p50-p65 heterodimer DNA binding and have identified the p50 monomer as a locus for inhibitory S-nitrosylation. We now show that the binding partner of p50, NF-kappaB p65, is also targeted by NO following cytokine stimulation of respiratory epithelial cells and macrophages and identify a conserved cysteine within the Rel homology domain that is the site for S-nitrosylation. S Nitrosylation of p65 inhibits NF-kappaB-dependent gene transcription, and nuclear levels of S-nitrosylated p65 correlate with decreased DNA binding of the p50-p65 heterodimer. NOS2 regulates cytokine-induced S-nitrosylation of p65, resulting in decreased NF-kappaB binding to the NOS2 promoter, thereby inhibiting further NOS2 expression. Collectively, these findings delineate a mechanism by which NOS2 modulates NF-kappaB activity and regulates gene expression in inflammation. PMID- 17720814 TI - The role of electrostatics in colicin nuclease domain translocation into bacterial cells. AB - The mechanism(s) by which nuclease colicins translocate distinct cytotoxic enzymes (DNases, rRNases, and tRNases) to the cytoplasm of Escherichia coli is unknown. Previous in vitro investigations on isolated colicin nuclease domains have shown that they have a strong propensity to associate with anionic phospholipid vesicles, implying that electrostatic interactions with biological membranes play a role in their import. In the present work we set out to test this hypothesis in vivo. We show that cell killing by the DNase toxin colicin E9 of E. coli HDL11, a strain in which the level of anionic phospholipid and hence inner membrane charge is regulated by isopropyl beta-D-thiogalactopyranoside induction, is critically dependent on the level of inducer, whereas this is not the case for pore-forming colicins that take the same basic route into the periplasm. Moreover, there is a strong correlation between the level and rate of HDL11 cell killing and the net positive charge on a colicin DNase, with similar effects seen for wild type E. coli cells, data that are consistent with a direct, electrostatically mediated interaction between colicin nucleases and the bacterial inner membrane. We next sought to identify how membrane-associated colicin nucleases might be translocated into the cell. We show that neither the Sec or Tat systems are involved in nuclease colicin uptake but that nuclease colicin toxicity is instead dependent on functional FtsH, an inner membrane AAA(+) ATPase and protease that dislocates misfolded membrane proteins to the cytoplasm for destruction. PMID- 17720815 TI - Knockdown of the intraflagellar transport protein IFT46 stimulates selective gene expression in mouse chondrocytes and affects early development in zebrafish. AB - Bone morphogenetic proteins (BMPs) act as multifunctional regulators in morphogenesis during development. In particular they play a determinant role in the formation of cartilage molds and their replacement by bone during endochondral ossification. In cell culture, BMP-2 favors chondrogenic expression and promotes hypertrophic maturation of chondrocytes. In mouse chondrocytes we have identified a BMP-2-sensitive gene encoding a protein of 301 amino acids. This protein, named mIFT46, is the mouse ortholog of recently identified Caenorhabditis elegans and Chlamydomonas reinhardtii intraflagellar transport (IFT) proteins. After generation of a polyclonal antibody against mIFT46, we showed for the first time that the endogenous protein is located in the primary cilium of chondrocytes. We also found that mIFT46 is preferentially expressed in early hypertrophic chondrocytes located in the growth plate. Additionally, mIFT46 knockdown by small interfering RNA oligonucleotides in cultured chondrocytes specifically stimulated the expression of several genes related to skeletogenesis. Furthermore, Northern blotting analysis indicated that mIFT46 is also expressed before chondrogenesis in embryonic mouse development, suggesting that the role of mIFT46 might not be restricted to cartilage. To explore the role of IFT46 during early development, we injected antisense morpholino oligonucleotides in Danio rerio embryos to reduce zebrafish IFT46 protein (zIFT46) synthesis. Dramatic defects in embryonic development such as a dorsalization and a tail duplication were observed. Thus our results taken together indicate that the ciliary protein IFT46 has a specific function in chondrocytes and is also essential for normal development of vertebrates. PMID- 17720816 TI - Interplay between Cernunnos-XLF and nonhomologous end-joining proteins at DNA ends in the cell. AB - Cernunnos-XLF is the most recently identified core component in the nonhomologous end-joining (NHEJ) pathway for the repair of DNA double strand breaks (DSBs) in mammals. It associates with the XRCC4/ligase IV ligation complex and stimulates its activity in a still unknown manner. NHEJ also requires the DNA-dependent protein kinase that contains a Ku70/Ku80 heterodimer and the DNA-dependent protein kinase catalytic subunit. To understand the interplay between Cernunnos XLF and the other proteins implicated in the NHEJ process, we have analyzed the interactions of Cernunnos-XLF and NHEJ proteins in cells after treatment with DNA double strand-breaking agents by means of a detergent-based cellular fractionation protocol. We report that Cernunnos-XLF is corecruited with the core NHEJ components on chromatin damaged with DSBs in human cells and is phosphorylated by the DNA-dependent protein kinase catalytic subunit. Our data show a pivotal role for DNA ligase IV in the NHEJ ligation complex assembly and recruitment to DSBs because the association of Cernunnos-XLF with the XRCC4/ligase IV complex relies primarily on the DNA ligase IV component, and an intact XRCC4/ligase IV complex is necessary for Cernunnos-XLF mobilization to damaged chromatin. Conversely, a Cernunnos-XLF defect has no apparent impact on the XRCC4/ligase IV association and recruitment to the DSBs or on the stimulation of the DNA-dependent protein kinase on DNA ends. PMID- 17720817 TI - The M18 aspartyl aminopeptidase of the human malaria parasite Plasmodium falciparum. AB - A member of the M18 family of aspartyl aminopeptidases is expressed by all intra erythrocytic stages of the human malaria parasite Plasmodium falciparum (PfM18AAP), with highest expression levels in rings. Functionally active recombinant enzyme, rPfM18AAP, and native enzyme in cytosolic extracts of malaria parasites are 560-kDa octomers that exhibit optimal activity at neutral pH and require the presence of metal ions to maintain enzymatic activity and stability. Like the human aspartyl aminopeptidase, the exopeptidase activity of PfM18AAP is exclusive to N-terminal acidic amino acids, glutamate and aspartate, making this enzyme of particular interest and suggesting that it may function alongside the malaria cytosolic neutral aminopeptidases in the release of amino acids from host hemoglobin-derived peptides. Whereas immunocytochemical studies using transgenic P. falciparum parasites show that PfM18AAP is expressed in the cytosol, immunoblotting experiments revealed that the enzyme is also trafficked out of the parasite into the surrounding parasitophorous vacuole. Antisense-mediated knockdown of PfM18AAP results in a lethal phenotype as a result of significant intracellular damage and validates this enzyme as a target at which novel antimalarial drugs could be directed. Novel phosphinic derivatives of aspartate and glutamate showed modest inhibition of rPfM18AAP but did not inhibit malaria growth in culture. However, we were able to draw valuable observations concerning the structure-activity relationship of these inhibitors that can be employed in future inhibitor optimization studies. PMID- 17720819 TI - Fine-scale genetic diversity among Burkholderia pseudomallei soil isolates in northeast Thailand. AB - Burkholderia pseudomallei soil isolates from northeast Thailand were genotyped using multiple-locus variable-number tandem repeat (VNTR) analysis (MLVA) and multilocus sequence typing (MLST). MLVA identified 19 genotypes within three clades, while MLST revealed two genotypes. These close genetic relationships imply a recent colonization followed by localized expansion, similar to what occurs in an outbreak situation. PMID- 17720818 TI - Rhizobial factors required for stem nodule maturation and maintenance in Sesbania rostrata-Azorhizobium caulinodans ORS571 symbiosis. AB - The molecular and physiological mechanisms behind the maturation and maintenance of N(2)-fixing nodules during development of symbiosis between rhizobia and legumes still remain unclear, although the early events of symbiosis are relatively well understood. Azorhizobium caulinodans ORS571 is a microsymbiont of the tropical legume Sesbania rostrata, forming N(2)-fixing nodules not only on the roots but also on the stems. In this study, 10,080 transposon-inserted mutants of A. caulinodans ORS571 were individually inoculated onto the stems of S. rostrata, and those mutants that induced ineffective stem nodules, as displayed by halted development at various stages, were selected. From repeated observations on stem nodulation, 108 Tn5 mutants were selected and categorized into seven nodulation types based on size and N(2) fixation activity. Tn5 insertions of some mutants were found in the well-known nodulation, nitrogen fixation, and symbiosis-related genes, such as nod, nif, and fix, respectively, lipopolysaccharide synthesis-related genes, C(4) metabolism-related genes, and so on. However, other genes have not been reported to have roles in legume-rhizobium symbiosis. The list of newly identified symbiosis-related genes will present clues to aid in understanding the maturation and maintenance mechanisms of nodules. PMID- 17720820 TI - Development of quantitative real-time PCR assays for detection and quantification of surrogate biological warfare agents in building debris and leachate. AB - Evaluation of the fate and transport of biological warfare (BW) agents in landfills requires the development of specific and sensitive detection assays. The objective of the current study was to develop and validate SYBR green quantitative real-time PCR (Q-PCR) assays for the specific detection and quantification of surrogate BW agents in synthetic building debris (SBD) and leachate. Bacillus atrophaeus (vegetative cells and spores) and Serratia marcescens were used as surrogates for Bacillus anthracis (anthrax) and Yersinia pestis (plague), respectively. The targets for SYBR green Q-PCR assays were the 16S-23S rRNA intergenic transcribed spacer (ITS) region and recA gene for B. atrophaeus and the gyrB, wzm, and recA genes for S. marcescens. All assays showed high specificity when tested against 5 ng of closely related Bacillus and Serratia nontarget DNA from 21 organisms. Several spore lysis methods that include a combination of one or more of freeze-thaw cycles, chemical lysis, hot detergent treatment, bead beat homogenization, and sonication were evaluated. All methods tested showed similar threshold cycle values. The limit of detection of the developed Q-PCR assays was determined using DNA extracted from a pure bacterial culture and DNA extracted from sterile water, leachate, and SBD samples spiked with increasing quantities of surrogates. The limit of detection for B. atrophaeus genomic DNA using the ITS and B. atrophaeus recA Q-PCR assays was 7.5 fg per PCR. The limits of detection of S. marcescens genomic DNA using the gyrB, wzm, and S. marcescens recA Q-PCR assays were 7.5 fg, 75 fg, and 7.5 fg per PCR, respectively. Quantification of B. atrophaeus vegetative cells and spores was linear (R(2) > 0.98) over a 7-log-unit dynamic range down to 10(1) B. atrophaeus cells or spores. Quantification of S. marcescens (R(2) > 0.98) was linear over a 6-log-unit dynamic range down to 10(2) S. marcescens cells. The developed Q-PCR assays are highly specific and sensitive and can be used for monitoring the fate and transport of the BW surrogates B. atrophaeus and S. marcescens in building debris and leachate. PMID- 17720821 TI - Mariner-based transposon mutagenesis of Rickettsia prowazekii. AB - Rickettsia prowazekii, the causative agent of epidemic typhus, is an obligate intracellular bacterium that grows directly within the cytoplasm of its host cell, unbounded by a vacuolar membrane. The obligate intracytoplasmic nature of rickettsial growth places severe restrictions on the genetic analysis of this distinctive human pathogen. In order to expand the repertoire of genetic tools available for the study of this pathogen, we have employed the versatile mariner based, Himar1 transposon system to generate insertional mutants of R. prowazekii. A transposon containing the R. prowazekii arr-2 rifampin resistance gene and a gene coding for a green fluorescent protein (GFP(UV)) was constructed and placed on a plasmid expressing the Himar1 transposase. Electroporation of this plasmid into R. prowazekii resulted in numerous transpositions into the rickettsial genome. Transposon insertion sites were identified by rescue cloning, followed by DNA sequencing. Random transpositions integrating at TA sites in both gene coding and intergenic regions were identified. Individual rickettsial clones were isolated by the limiting-dilution technique. Using both fixed and live-cell techniques, R. prowazekii transformants expressing GFP(UV) were easily visible by fluorescence microscopy. Thus, a mariner-based system provides an additional mechanism for generating rickettsial mutants that can be screened using GFP(UV) fluorescence. PMID- 17720822 TI - Comparison of ergot alkaloid biosynthesis gene clusters in Claviceps species indicates loss of late pathway steps in evolution of C. fusiformis. AB - The grass parasites Claviceps purpurea and Claviceps fusiformis produce ergot alkaloids (EA) in planta and in submerged culture. Whereas EA synthesis (EAS) in C. purpurea proceeds via clavine intermediates to lysergic acid and the complex ergopeptines, C. fusiformis produces only agroclavine and elymoclavine. In C. purpurea the EAS gene (EAS) cluster includes dmaW (encoding the first pathway step), cloA (elymoclavine oxidation to lysergic acid), and the lpsA/lpsB genes (ergopeptine formation). We analyzed the corresponding C. fusiformis EAS cluster to investigate the evolutionary basis for chemotypic differences between the Claviceps species. Other than three peptide synthetase genes (lpsC and the tandem paralogues lpsA1 and lpsA2), homologues of all C. purpurea EAS genes were identified in C. fusiformis, including homologues of lpsB and cloA, which in C. purpurea encode enzymes for steps after clavine synthesis. Rearrangement of the cluster was evident around lpsB, which is truncated in C. fusiformis. This and several frameshift mutations render CflpsB a pseudogene (CflpsB(Psi)). No obvious inactivating mutation was identified in CfcloA. All C. fusiformis EAS genes, including CflpsB(Psi) and CfcloA, were expressed in culture. Cross complementation analyses demonstrated that CfcloA and CflpsB(Psi) were expressed in C. purpurea but did not encode functional enzymes. In contrast, CpcloA catalyzed lysergic acid biosynthesis in C. fusiformis, indicating that C. fusiformis terminates its EAS pathway at elymoclavine because the cloA gene product is inactive. We propose that the C. fusiformis EAS cluster evolved from a more complete cluster by loss of some lps genes and by rearrangements and mutations inactivating lpsB and cloA. PMID- 17720823 TI - Inactivation of Bacillus anthracis spores by liquid biocides in the presence of food residue. AB - Biocide inactivation of Bacillus anthracis spores in the presence of food residues after a 10-min treatment time was investigated. Spores of nonvirulent Bacillus anthracis strains 7702, ANR-1, and 9131 were mixed with water, flour paste, whole milk, or egg yolk emulsion and dried onto stainless-steel carriers. The carriers were exposed to various concentrations of peroxyacetic acid, sodium hypochlorite (NaOCl), or hydrogen peroxide (H(2)O(2)) for 10 min at 10, 20, or 30 degrees C, after which time the survivors were quantified. The relationship between peroxyacetic acid concentration, H(2)O(2) concentration, and spore inactivation followed a sigmoid curve that was accurately described using a four parameter logistic model. At 20 degrees C, the minimum concentrations of peroxyacetic acid, H(2)O(2), and NaOCl (as total available chlorine) predicted to inactivate 6 log(10) CFU of B. anthracis spores with no food residue present were 1.05, 23.0, and 0.78%, respectively. At 10 degrees C, sodium hypochlorite at 5% total available chlorine did not inactivate more than 4 log(10) CFU. The presence of the food residues had only a minimal effect on peroxyacetic acid and H(2)O(2) sporicidal efficacy, but the efficacy of sodium hypochlorite was markedly inhibited by whole-milk and egg yolk residues. Sodium hypochlorite at 5% total available chlorine provided no greater than a 2-log(10) CFU reduction when spores were in the presence of egg yolk residue. This research provides new information regarding the usefulness of peroxygen biocides for B. anthracis spore inactivation when food residue is present. This work also provides guidance for adjusting decontamination procedures for food-soiled and cold surfaces. PMID- 17720824 TI - Cryptosporidium genotypes in wildlife from a new york watershed. AB - To identify the animal sources for Cryptosporidium contamination, we genotyped Cryptosporidium spp. in wildlife from the watershed of the New York City drinking water supply, using a small-subunit rRNA gene-based PCR-restriction fragment length polymorphism analysis and DNA sequencing. A total of 541 specimens from 38 species of wildlife were analyzed. One hundred and eleven (20.5%) of the wildlife specimens were PCR positive. Altogether, 21 Cryptosporidium genotypes were found in wildlife samples, 11 of which were previously found in storm runoff in the watershed, and six of these 11 were from storm water genotypes of unknown animal origin. Four new genotypes were found, and the animal hosts for four storm water genotypes were expanded. With the exception of the cervine genotype, most genotypes were found in a limited number of animal species and have no major public health significance. PMID- 17720825 TI - Ralstonia solanacearum strains from Martinique (French West Indies) exhibiting a new pathogenic potential. AB - We investigated a destructive pathogenic variant of the plant pathogen Ralstonia solanacearum that was consistently isolated in Martinique (French West Indies). Since the 1960s, bacterial wilt of solanaceous crops in Martinique has been caused primarily by strains of R. solanacearum that belong to either phylotype I or phylotype II. Since 1999, anthurium shade houses have been dramatically affected by uncharacterized phylotype II strains that also affected a wide range of species, such as Heliconia caribea, cucurbitaceous crops, and weeds. From 1989 to 2003, a total of 224 R. solanacearum isolates were collected and compared to 6 strains isolated in Martinique in the 1980s. The genetic diversity and phylogenetic position of selected strains from Martinique were assessed (multiplex PCRs, mutS and egl DNA sequence analysis) and compared to the genetic diversity and phylogenetic position of 32 reference strains covering the known diversity within the R. solanacearum species complex. Twenty-four representative isolates were tested for pathogenicity to Musa species (banana) and tomato, eggplant, and sweet pepper. Based upon both PCR and sequence analysis, 119 Martinique isolates from anthurium, members of the family Cucurbitaceae, Heliconia, and tomato, were determined to belong to a group termed phylotype II/sequevar 4 (II/4). While these strains cluster with the Moko disease-causing strains, they were not pathogenic to banana (NPB). The strains belonging to phylotype II/4NPB were highly pathogenic to tomato, eggplant, and pepper, were able to wilt the resistant tomato variety Hawaii7996, and may latently infect cooking banana. Phylotype II/4NPB constitutes a new pathogenic variant of R. solanacearum that has recently appeared in Martinique and may be latently prevalent throughout Caribbean and Central/South America. PMID- 17720826 TI - Incubation of environmental samples in a diffusion chamber increases the diversity of recovered isolates. AB - The majority of microorganisms from natural environments cannot be grown in the laboratory. The diffusion-chamber-based approach is an alternative method that allows microorganisms to grow in their natural environment. An inoculum is sandwiched between semipermeable (0.03-mum-pore-size) membranes of the chamber, which is then returned to the source environment. The chamber allows for a free exchange of chemicals with the external milieu by diffusion while restricting the movement of cells. We used freshwater pond sediment to inoculate diffusion chambers and petri dishes. The diffusion chambers were incubated on top of the sediment for 4 weeks. Both chamber and petri dish cultivation resulted in the isolation of numerous representatives of Alpha-, Beta-, and Gammaproteobacteria; Actinobacteria; Firmicutes; and Bacteroidetes. However, the diffusion-chamber based approach also led to the isolation of species from rarely cultivated groups, such as Deltaproteobacteria, Verrucomicrobia, Spirochaetes, and Acidobacteria. Material from the chambers was also transferred to new chambers in order to learn whether this will increase the recovery of isolates. Several isolates could be obtained only from material transferred through multiple diffusion chambers. This suggests that continuous cultivation in diffusion chambers adapts some microorganisms for growth under otherwise prohibitive in vitro conditions. PMID- 17720827 TI - Microarray-based characterization of the Listeria monocytogenes cold regulon in log- and stationary-phase cells. AB - Whole-genome microarray experiments were performed to define the Listeria monocytogenes cold growth regulon and to identify genes differentially expressed during growth at 4 and 37 degrees C. Microarray analysis using a stringent cutoff (adjusted P < 0.001; >/=2.0-fold change) revealed 105 and 170 genes that showed higher transcript levels in logarithmic- and stationary-phase cells, respectively, at 4 degrees C than in cells grown at 37 degrees C. A total of 74 and 102 genes showed lower transcript levels in logarithmic- and stationary-phase cells, respectively, grown at 4 degrees C. Genes with higher transcript levels at 4 degrees C in both stationary- and log-phase cells included genes encoding a two component response regulator (lmo0287), a cold shock protein (cspL), and two RNA helicases (lmo0866 and lmo1722), whereas a number of genes encoding virulence factors and heat shock proteins showed lower transcript levels at 4 degrees C. Selected genes that showed higher transcript levels at 4 degrees C during both stationary and log phases were confirmed by quantitative reverse transcriptase PCR. Our data show that (i) a large number of L. monocytogenes genes are differentially expressed at 4 and 37 degrees C, with more genes showing higher transcript levels than lower transcript levels at 4 degrees C, (ii) L. monocytogenes genes with higher transcript levels at 4 degrees C include a number of genes and operons with previously reported or plausible roles in cold adaptation, and (iii) L. monocytogenes genes with lower transcript levels at 4 degrees C include a number of virulence and virulence-associated genes as well as some heat shock genes. PMID- 17720828 TI - Inhibition of fungal and bacterial plant pathogens in vitro and in planta with ultrashort cationic lipopeptides. AB - Plant diseases constitute an emerging threat to global food security. Many of the currently available antimicrobial agents for agriculture are highly toxic and nonbiodegradable and cause extended environmental pollution. Moreover, an increasing number of phytopathogens develop resistance to them. Recently, we have reported on a new family of ultrashort antimicrobial lipopeptides which are composed of only four amino acids linked to fatty acids (A. Makovitzki, D. Avrahami, and Y. Shai, Proc. Natl. Acad. Sci. USA 103:15997-16002, 2006). Here, we investigated the activities in vitro and in planta and the modes of action of these short lipopeptides against plant-pathogenic bacteria and fungi. They act rapidly, at low micromolar concentrations, on the membranes of the microorganisms via a lytic mechanism. In vitro microscopic analysis revealed wide-scale damage to the microorganism's membrane, in addition to inhibition of pathogen growth. In planta potent antifungal activity was demonstrated on cucumber fruits and leaves infected with the pathogen Botrytis cinerea as well as on corn leaves infected with Cochliobolus heterostrophus. Similarly, treatment with the lipopeptides of Arabidopsis leaves infected with the bacterial leaf pathogen Pseudomonas syringae efficiently and rapidly reduced the number of bacteria. Importantly, in contrast to what occurred with many native lipopeptides, no toxicity was observed on the plant tissues. These data suggest that the ultrashort lipopeptides could serve as native-like antimicrobial agents economically feasible for use in plant protection. PMID- 17720829 TI - Zoo animals as reservoirs of gram-negative bacteria harboring integrons and antimicrobial resistance genes. AB - A total of 232 isolates of gram-negative bacteria were recovered from mammals, reptiles, and birds housed at Asa Zoological Park, Hiroshima prefecture, Japan. Forty-nine isolates (21.1%) showed multidrug resistance phenotypes and harbored at least one antimicrobial resistance gene. PCR and DNA sequencing identified class 1 and class 2 integrons and many beta-lactamase-encoding genes, in addition to a novel AmpC beta-lactamase gene, bla(CMY-26). Furthermore, the plasmid mediated quinolone resistance genes qnr and aac(6')-Ib-cr were also identified. PMID- 17720830 TI - Localization and visualization of a coxiella-type symbiont within the lone star tick, Amblyomma americanum. AB - A Coxiella-type microbe occurs at 100% frequency in all Amblyomma americanum ticks thus far tested. Using laboratory-reared ticks free of other microbes, we identified the Amblyomma-associated Coxiella microbe in several types of tissue and at various stages of the life cycle of A. americanum by 16S rRNA gene sequencing and diagnostic PCR. We visualized Amblyomma-associated Coxiella through the use of a diagnostic fluorescence in situ hybridization (FISH) assay supplemented with PCR-based detection, nucleic acid fluorescent staining, wide field epifluorescence and confocal microscopy, and transmission electron microscopy (TEM). Specific fluorescent foci were observed in several tick tissues, including the midgut and the Malpighian tubules, but particularly bright signals were observed in the granular acini of salivary gland clusters and in both small and large oocytes. TEM confirmed intracellular bacterial structures in the same tissues. The presence of Amblyomma-associated Coxiella within oocytes is consistent with the vertical transmission of these endosymbionts. Further, the presence of the Amblyomma-associated Coxiella symbiont in other tissues such as salivary glands could potentially lead to interactions with horizontally acquired pathogens. PMID- 17720831 TI - Variability of bacterial biofilms of the "tina" wood vats used in the ragusano cheese-making process. AB - Ragusano cheese is a "protected denomination of origin" cheese made in the Hyblean region of Sicily from raw milk using traditional wooden tools, without starter. To explore the Ragusano bacterial ecosystem, molecular fingerprinting was conducted at different times during the ripening and biofilms from the wooden vats called "tinas" were investigated. Raw milks collected at two farm sites, one on the mountain and one at sea level, were processed to produce Ragusano cheese. Raw milk, curd before and after cooking, curd at stretching time (cheese 0 time), and cheese samples (4 and 7 months) were analyzed by PCR-temporal temperature gel electrophoresis (PCR-TTGE) and by classical enumeration microbiology. With the use of universal primers, PCR-TTGE revealed many differences between the raw milk profiles, but also notable common bands identified as Streptococcus thermophilus, Lactobacillus lactis, Lactobacillus delbrueckii, and Enterococcus faecium. After the stretching, TTGE profiles revealed three to five dominant species only through the entire process of ripening. In the biofilms of the two tinas used, one to five species were detected, S. thermophilus being predominant in both. Biofilms from five other tinas were also analyzed by PCR-TTGE, PCR-denaturating gradient gel electrophoresis, specific PCR tests, and sequencing, confirming the predominance of lactic acid bacteria (S. thermophilus, L. lactis, and L. delbrueckii subsp. lactis) and the presence of a few high-GC-content species, like coryneform bacteria. The spontaneous acidification of raw milks before and after contact with the five tinas was followed in two independent experiments. The lag period before acidification can be up to 5 h, depending on the raw milk and the specific tina, highlighting the complexity of this natural inoculation system. PMID- 17720832 TI - Cultivation-independent analysis of fungal genotypes in soil by using simple sequence repeat markers. AB - Cultivation-independent analyses of fungi are used for community profiling as well as identification of specific strains in environmental samples. The objective of the present study was to adapt genotyping based on simple sequence repeat (SSR) marker detection for use in cultivation-independent monitoring of fungal species or strains in bulk soil DNA. As a model system, a fungal biocontrol agent (BCA) based on Beauveria brongniartii, for which six SSR markers have been developed, was used. Species specificity of SSR detection was verified with 15 fungal species. Real-time PCR was used to adjust for different detection sensitivities of the six SSR markers as well as for different template quantities. The limit for reliable detection per PCR assay was below 2 pg target DNA, corresponding to an estimated 45 genome copies of B. brongniartii. The cultivation-independent approach was compared to cultivation-dependent SSR analysis with soil samples from a B. brongniartii BCA-treated field plot. Results of the cultivation-independent method were consistent with cultivation-dependent genotyping and allowed for unambiguous identification and differentiation of the applied as well as indigenous strains in the samples. Due to the larger quantities of soil used for cultivation-dependent analysis, its sensitivity was higher, but cultivation-independent SSR genotyping was much faster. Therefore, cultivation-independent monitoring of B. brongniartii based on multiple SSR markers represents a rapid and strain-specific approach. This strategy may also be applicable to other fungal species or strains for which SSR markers have been developed. PMID- 17720833 TI - Identification of N-acetylhexosamine 1-kinase in the complete lacto-N-biose I/galacto-N-biose metabolic pathway in Bifidobacterium longum. AB - We have determined the functions of the enzymes encoded by the lnpB, lnpC, and lnpD genes, located downstream of the lacto-N-biose phosphorylase gene (lnpA), in Bifidobacterium longum JCM1217. The lnpB gene encodes a novel kinase, N acetylhexosamine 1-kinase, which produces N-acetylhexosamine 1-phosphate; the lnpC gene encodes UDP-glucose hexose 1-phosphate uridylyltransferase, which is also active on N-acetylhexosamine 1-phosphate; and the lnpD gene encodes a UDP glucose 4-epimerase, which is active on both UDP-galactose and UDP-N acetylgalactosamine. These results suggest that the gene operon lnpABCD encodes a previously undescribed lacto-N-biose I/galacto-N-biose metabolic pathway that is involved in the intestinal colonization of bifidobacteria and that utilizes lacto N-biose I from human milk oligosaccharides or galacto-N-biose from mucin sugars. PMID- 17720834 TI - Comparison of direct genome restriction enzyme analysis and pulsed-field gel electrophoresis for typing of Vibrio vulnificus and their correspondence with multilocus sequence typing data. AB - We compared the potential of direct genome restriction enzyme analysis (DGREA) and pulsed-field gel electrophoresis (PFGE) for discriminating Vibrio vulnificus isolates from clinical (23) and environmental (17) sources. The genotypes generated by both methodologies were compared to previous multilocus sequence typing (MLST) data. DGREA established clearer relationships among V. vulnificus strains and was more consistent with MLST than with PFGE. DGREA is a very promising tool for epidemiological and ecological studies of V. vulnificus. PMID- 17720835 TI - Genetic screen for regulatory mutations in Methanococcus maripaludis and its use in identification of induction-deficient mutants of the euryarchaeal repressor NrpR. AB - NrpR is an euryarchaeal transcriptional repressor of nitrogen assimilation genes. Previous studies with Methanococcus maripaludis demonstrated that NrpR binds to palindromic operator sequences, blocking transcription initiation. The metabolite 2-oxoglutarate, an indicator of cellular nitrogen deficiency, induces transcription by lowering the affinity of NrpR for operator DNA. In this report we build on existing genetic tools for M. maripaludis to develop a screen for change-of-function mutations in a transcriptional regulator and demonstrate the use of an X-Gal (5-bromo-4-chloro-3-indolyl-beta-d-galactopyranoside) screen for strict anaerobes. We use the approach to address the primary structural requirements for the response of NrpR to 2-oxoglutarate. nrpR genes from the mesophilic M. maripaludis and the hyperthermophilic Methanopyrus kandleri were targeted for mutagenesis. M. maripaludis nrpR encodes a protein with two homologous NrpR domains while the M. kandleri nrpR homolog encodes a single NrpR domain. Random point mutagenesis and alanine replacement mutagenesis identified two amino acid residues of M. kandleri NrpR involved in induction of gene expression under nitrogen-deficient conditions and thus in the response to 2 oxoglutarate. Mutagenesis of the corresponding regions in either domain of M. maripaludis NrpR resulted in a similar effect, demonstrating a conserved structure-function relationship between the two repressors. The results indicate that in M. maripaludis, both NrpR domains participate in the 2-oxoglutarate response. The approach used here has wide adaptability to other regulatory systems in methanogenic Archaea and other strict anaerobes. PMID- 17720836 TI - Isolation, characterization, and ecology of sulfur-respiring crenarchaea inhabiting acid-sulfate-chloride-containing geothermal springs in Yellowstone National Park. AB - Elemental sulfur (S(0)) is associated with many geochemically diverse hot springs, yet little is known about the phylogeny, physiology, and ecology of the organisms involved in its cycling. Here we report the isolation, characterization, and ecology of two novel, S(0)-reducing Crenarchaea from an acid geothermal spring referred to as Dragon Spring. Isolate 18U65 grows optimally at 70 to 72 degrees C and at pH 2.5 to 3.0, while isolate 18D70 grows optimally at 81 degrees C and pH 3.0. Both isolates are chemoorganotrophs, dependent on complex peptide-containing carbon sources, S(0), and anaerobic conditions for respiration-dependent growth. Glycerol dialkyl glycerol tetraethers (GDGTs) containing four to six cyclopentyl rings were present in the lipid fraction of isolates 18U65 and 18D70. Physiological characterization suggests that the isolates are adapted to the physicochemical conditions of Dragon Spring and can utilize the natural organic matter in the spring as a carbon and energy source. Quantitative PCR analysis of 16S rRNA genes associated with the S(0) flocs recovered from several acid geothermal springs using isolate specific primers indicates that these two populations together represent 17 to 37% of the floc-associated DNA. The physiological characteristics of isolates 18U65 and 18D70 are consistent with their potential widespread distribution and putative role in the cycling of sulfur in acid geothermal springs throughout the Yellowstone National Park geothermal complex. Based on phenotypic and genetic characterization, the designations Caldisphaera draconis sp. nov. and Acidilobus sulfurireducens sp. nov. are proposed for isolates 18U65 and 18D70, respectively. PMID- 17720837 TI - Membrane-bound, 2-keto-D-gluconate-yielding D-gluconate dehydrogenase from "Gluconobacter dioxyacetonicus" IFO 3271: molecular properties and gene disruption. AB - Most Gluconobacter species produce and accumulate 2-keto-d-gluconate (2KGA) and 5KGA simultaneously from d-glucose via GA in culture medium. 2KGA is produced by membrane-bound flavin adenine dinucleotide-containing GA 2-dehydrogenase (FAD GADH). FAD-GADH was purified from "Gluconobacter dioxyacetonicus" IFO 3271, and N terminal sequences of the three subunits were analyzed. PCR primers were designed from the N-terminal sequences, and part of the FAD-GADH genes was cloned as a PCR product. Using this PCR product, gene fragments containing whole FAD-GADH genes were obtained, and finally the nucleotide sequence of 9,696 bp was determined. The cloned sequence had three open reading frames (ORFs), gndS, gndL, and gndC, corresponding to small, large, and cytochrome c subunits of FAD-GADH, respectively. Seven other ORFs were also found, one of which showed identity to glucono-delta-lactonase, which might be involved directly in 2KGA production. Three mutant strains defective in either gndL or sldA (the gene responsible for 5KGA production) or both were constructed. Ferricyanide-reductase activity with GA in the membrane fraction of the gndL-defective strain decreased by about 60% of that of the wild-type strain, while in the sldA-defective strain, activity with GA did not decrease and activities with glycerol, d-arabitol, and d-sorbitol disappeared. Unexpectedly, the strain defective in both gndL and sldA (double mutant) still showed activity with GA. Moreover, 2KGA production was still observed in gndL and double mutant strains. 5KGA production was not observed at all in sldA and double mutant strains. Thus, it seems that "G. dioxyacetonicus" IFO 3271 has another membrane-bound enzyme that reacts with GA, producing 2KGA. PMID- 17720838 TI - Low-pH adaptation and the acid tolerance response of Bifidobacterium longum biotype longum. AB - Bifidobacteria are one of the main microbial inhabitants of the human colon. Usually administered in fermented dairy products as beneficial microorganisms, they have to overcome the acidic pH found in the stomach during the gastrointestinal transit to be able to colonize the lower parts of the intestine. The mechanisms underlying acid response and adaptation in Bifidobacterium longum biotype longum NCIMB 8809 and its acid-pH-resistant mutant B. longum biotype longum 8809dpH were studied. Comparison of protein maps, and protein identification by matrix-assisted laser desorption ionization-time of flight mass spectrometry analysis, allowed us to identify nine different proteins whose production largely changed in the mutant strain. Furthermore, the production of 47 proteins was modulated by pH in one or both strains. These included general stress response chaperones and proteins involved in transcription and translation as well as in carbohydrate and nitrogen metabolism, among others. Significant differences in the levels of metabolic end products and in the redox status of the cells were also detected between the wild-type strain and its acid-pH resistant mutant in response to, or as a result of, adaptation to acid. Remarkably, the results of this work indicated that adaptation and response to low pH in B. longum biotype longum involve changes in the glycolytic flux and in the ability to regulate the internal pH. These changes were accompanied by a higher content of ammonium in the cytoplasm, likely coming from amino acid deamination, and a decrease of the bile salt hydrolase activity. PMID- 17720839 TI - Seasonal detection of human viruses and coliphage in Newport Bay, California. AB - Recent studies have shown that the fecal indicator bacteria (FIB) currently used to indicate water quality in the coastal environment may be inadequate to reflect human viral contamination. Coliphage was suggested as a better indicator of human viral pollution and was proposed by the U.S. EPA as an alternative indicator for fecal pollution in groundwater. In this study, we investigated the occurrence and distribution of FIB, F+ coliphage, and PCR-detectable human adenovirus and enterovirus for an entire year at 15 locations around the Newport Bay watershed, an important southern California estuary for water recreation and an ecological reserve. Peak concentrations and prevalences of FIB and F+ coliphage were associated with winter storms (wet weather). Human adenoviruses and enteroviruses, however, were detected by PCR in approximately 5% of samples collected in the summer (dry weather) but only once in wet weather. These results demonstrated that FIB and coliphage have similar seasonal and freshwater-to saltwater distribution patterns, while the detection of human viruses depends on a distribution pattern that is the opposite of that of FIB and coliphage. This research suggested that coliphage and FIB share similar environmental sources, while sources of human viruses in Newport Bay are perhaps different. PMID- 17720840 TI - Immunoglobulins to surface-associated biofilm immunogens provide a novel means of visualization of methicillin-resistant Staphylococcus aureus biofilms. AB - Antigens from the methicillin-resistant Staphylococcus aureus (MRSA) cell wall have been shown to be immunogenic in vivo and upregulated during biofilm growth. In this study, we created purified, recombinant forms of selected antigens and biofilm-upregulated, cell wall-associated proteins. These proteins were shown to cause a robust polyclonal immunoglobulin G (IgG) response when used to immunize rabbits. Antibodies against these recombinant proteins bound to the native forms of each protein as harvested from in vitro grown biofilms of MRSA, as determined both via Western blot analysis and immunofluorescence confocal microscopy. These IgGs could be utilized as imaging tools that localize to areas of specific protein production within a biofilm. This work illustrates that immunogenic, cell wall-associated, biofilm-upregulated proteins are promising for in vitro visualization of biofilm growth, architecture, and space-function relationships. PMID- 17720841 TI - The ability of Aneurinibacillus migulanus (Bacillus brevis) to produce the antibiotic gramicidin S is correlated with phenotype variation. AB - Phenotype instability of bacterial strains can cause significant problems in biotechnological applications, since industrially useful properties may be lost. Here we report such degenerative dissociation for Aneurinibacillus migulanus (formerly known as Bacillus brevis) an established producer of the antimicrobial peptide gramicidin S (GS). Phenotypic variations within and between various strains maintained in different culture collections are demonstrated. The type strain, ATCC 9999, consists of six colony morphology variants, R, RC, RP, RT, SC, and SP, which were isolated and characterized as pure cultures. Correlations between colony morphology, growth, GS production, spore formation, and resistance to their own antimicrobial peptide were established in this study. We found the original R form to be the best producer, followed by RC, RP, and RT, while SC and SP yielded no GS at all. Currently available ATCC 9999(T) contains only 2% of the original R producer and is dominated by the newly described phenotypes RC and RP. No original R form is detected in the nominally equivalent strain DSM 2895(T) (=ATCC 9999(T)), which grows only as SC and SP phenotypes and has thus completely lost its value as a peptide producer. Two other strains from the same collection, DSM 5668 and DSM 5759, contain the unproductive SC variant and the GS-producing RC form, respectively. We describe the growth and maintenance conditions that stabilize certain colony phenotypes and reduce the degree of degenerative dissociation, thus providing a recommendation for how to revert the nonproducing smooth phenotypes to the valuable GS-producing rough ones. PMID- 17720842 TI - Molecular subtyping and genetic analysis of the enterohemolysin gene (ehxA) from Shiga toxin-producing escherichia coli and atypical enteropathogenic E. coli. AB - Analyses of the distribution of virulence factors among different Escherichia coli pathotypes, including Shiga toxin-producing E. coli (STEC), may provide some insight into the mechanisms by which different E. coli strains cause disease and the evolution of distinct E. coli types. The aim of this study was to examine the DNA sequence of the gene for enterohemolysin, a plasmid-encoded toxin that readily causes the hemolysis of washed sheep erythrocytes, and to assess the distribution of enterohemolysin subtypes among E. coli isolates from various human and animal sources. The 2,997-bp ehxA gene was amplified from 227 (63.8%) of 356 stx- and/or eae-positive E. coli strains isolated from cattle and sheep and from 24 (96.0%) of 25 STEC strains isolated from humans with diarrheal disease. By using PCR and restriction fragment length polymorphism (RFLP) analysis of ehxA, six distinct PCR-RFLP types (A to F) were observed, with strains of subtypes A and C constituting 91.6% of all the ehxA-positive strains. Subtype A was associated mainly with ovine strains with stx only (P < 0.001), and subtype C was associated with bovine eae-positive strains (P < 0.001). Eleven ehxA alleles were fully sequenced, and the phylogenetic analysis indicated the presence of three closely related (>95.0%) ehxA sequence groups, one including eae-positive strains (subtypes B, C, E, and F) and the other two including mainly eae-negative STEC strains (subtypes A and D). In addition to being widespread among STEC strains, stx-negative, eae-positive strains (atypical enteropathogenic E. coli strains) isolated from cattle and sheep have similar ehxA subtypes and hemolytic activities. PMID- 17720843 TI - Novel whole-cell antibiotic biosensors for compound discovery. AB - Cells containing reporters which are specifically induced via selected promoters are used in pharmaceutical drug discovery and in environmental biology. They are used in screening for novel drug candidates and in the detection of bioactive compounds in environmental samples. In this study, we generated and validated a set of five Bacillus subtilis promoters fused to the firefly luciferase reporter gene suitable for cell-based screening, enabling the as yet most-comprehensive high-throughput diagnosis of antibiotic interference in the major biosynthetic pathways of bacteria: the biosynthesis of DNA by the yorB promoter, of RNA by the yvgS promoter, of proteins by the yheI promoter, of the cell wall by the ypuA promoter, and of fatty acids by the fabHB promoter. The reporter cells mainly represent novel antibiotic biosensors compatible with high-throughput screening. We validated the strains by developing screens with a set of 14,000 pure natural products, representing a source of highly diverse chemical entities, many of them with antibiotic activity (6% with anti-Bacillus subtilis activity of 3.9, p < 0.01). Sleep bruxers were distributed among three heterogeneous groups. Sleep bruxers with low frequencies of orofacial activities were more at risk of reporting pain. PMID- 17720852 TI - Jaw clenching: muscle and joint forces, optimization strategies. AB - Realistic masticatory muscle and temporomandibular joint forces generated during bilateral jaw clenching are largely unknown. To determine which clenching directions load masticatory muscles and temporomandibular joints most heavily, we investigated muscle and joint forces based on feedback-controlled electromyograms of all jaw muscles, lines of action, geometrical data from the skull, and physiological cross-sectional areas acquired from the same individuals. To identify possible motor control strategies, we applied objective functions. The medial pterygoid turned out to be the most heavily loaded muscle for all bite directions. Biting with accentuated horizontal force components provoked the highest loading within the medial and lateral pterygoids. The largest joint forces were also found for these bite directions. Conversely, the lowest joint forces were detected during vertical biting. Additionally, joint forces with a clear posterior orientation were found. Optimization strategies with the elastic energy as objective function revealed the best fit with the calculated results. PMID- 17720853 TI - Hop bract polyphenols reduced three-day dental plaque regrowth. AB - Previous research has shown the inhibitory effects of hop bract polyphenols (HBP) on cariogenic streptococci in vitro, but their effects in humans have not been investigated. This double-blind, crossover clinical study tested the hypothesis that HBP delivered in a mouthrinse suppresses plaque regrowth in humans. Twenty nine healthy male volunteers had all plaque removed, and refrained from all oral hygiene for 3 days, except for rinsing with a mouthrinse containing 0.1% HBP or a placebo. The results showed that the mean amount of plaque assessed by the Patient Hygiene Performance score after the volunteers used the HBP mouthrinse was significantly less than that after they used the placebo (p < 0.001). The number of mutans streptococci in the plaque samples after volunteers used the HBP mouthrinse was significantly lower than that after they used the placebo (p < 0.05). These findings suggested that HBP, delivered in a mouthrinse, successfully reduced dental plaque regrowth in humans. PMID- 17720854 TI - Depression as a risk factor for denture dissatisfaction. AB - Depression is associated with impaired health outcomes. This study investigated whether there is a significant association between depression and dissatisfaction with dentures in older adults. In a population-based study (1180 adults aged 65 74 yrs), depression was measured by an abbreviated Geriatric Depression Scale. Denture dissatisfaction was assessed with a five-point Likert-type question ("very dissatisfied" to "very satisfied"). The depression-denture dissatisfaction association was analyzed with simple (dissatisfied vs. not dissatisfied outcome) and ordinal logistic regression (based on outcome's full range). For each unit increase on the 15-point depression scale, the probability of denture dissatisfaction increased by 24% [95% confidence interval, 15-34%, P < 0.001 (simple logistic regression)] and the probability for higher levels on the five point dissatisfaction scale increased by 16% [95% CI, 11-22%, P < 0.001 (ordinal logistic regression)], adjusted for potential confounding variables. The likely causal association in older adults has major implications for the evaluation of treatment effects and the demand for prosthodontic therapy. PMID- 17720855 TI - Dentin in severe fluorosis: a quantitative histochemical study. AB - Dentin responds to different alterations in the enamel with hypermineralization, and is a biomarker of fluoride exposure. We hypothesized that severe fluorosis would lead to hypermineralization of the dentin when the enamel was severely affected. We used scanning electron microscopy and quantitative electron-probe microanalysis to compare dentin and enamel from healthy and fluorotic teeth. The dentin in fluorotic teeth was characterized by a highly mineralized sclerotic pattern, in comparison with control teeth (p < 0.001) and fluorotic enamel lesions (p < 0.001). Enamel near the lesions showed hypercalcification in comparison with dentin (p < 0.001). In response to the effects of severe fluorosis in the enamel, the dentin showed hypermineralization, as found in other enamel disorders. The hypermineralization response of the dentin in our samples suggests that the mechanism of the response should be taken into account in dental caries and other dental disorders associated with severe fluorosis. PMID- 17720857 TI - Pre-overloading to extend fatigue life of cast clasps. AB - Permanent deformation in bending is associated with the development of residual stresses. The objective of this study was to characterize those residual stresses and test whether they can be manipulated to extend the fatigue lives of cast clasps. Simulations with validated non-linear finite element models were used to characterize the residual stresses in clasps cast from Ti-6Al-7Nb, Co-Cr, and Type IV gold alloys. In addition, two groups of as-cast and pre-overloaded (subjected to a load that produced 20 microm of permanent deformation) Ti-6Al-7Nb clasps (10 specimens each) were subjected to cyclic 0.5-mm deflections at 5 Hz until fatigue. Pre-overloaded specimens demonstrated significantly longer fatigue lives (32,200 +/- 17,300 cycles) than did those tested in the as-cast condition (17,900 +/- 7600 cycles), consistent with the maximum tensile stress values revealed by finite element analysis. PMID- 17720856 TI - Molecular analysis of healing at a bone-implant interface. AB - While bone healing occurs around implants, the extent to which this differs from healing at sites without implants remains unknown. We tested the hypothesis that an implant surface may affect the early stages of healing. In a new mouse model, we made cellular and molecular evaluations of healing at bone-implant interfaces vs. empty cortical defects. We assessed healing around Ti-6Al-4V, poly(L-lactide co-D,L,-lactide), and 303 stainless steel implants with surface characteristics comparable with those of commercial implants. Our qualitative cellular and molecular evaluations showed that osteoblast differentiation and new bone deposition began sooner around the implants, suggesting that the implant surface and microenvironment around implants favored osteogenesis. The general stages of healing in this mouse model resembled those in larger animal models, and supported the use of this new model as a test bed for studying cellular and molecular responses to biomaterial and biomechanical conditions. PMID- 17720858 TI - Inhibition of SFRP1 reduces severity of periodontitis. AB - Porphyromonas gingivalis (P. gingivalis) is implicated as a major pathogen in periodontitis, a common infectious disease characterized by the inflammation and destruction of periodontal tissues. Secreted frizzled-related protein 1 (SFRP1) modulates apoptosis in different cell types. To characterize the roles of SFRP1 in periodontitis, we used a P. gingivalis-induced murine periodontitis model. Inflammatory responses were measured by morphometric and histomorphometric analysis, apoptosis assay, and immunohistochemistry. We found that P. gingivalis infected mouse periodontal tissues expressed significantly more SFRP1 compared with those of control mice. Also, in P. gingivalis-infected animals, more apoptosis of inflammatory cells, fibroblasts, and bone-lining cells was observed compared with controls. Antibody experiments aimed at inhibiting SFRP1 expression in periodontitis resulted in a reduction of periodontal breakdown, inflammatory cell infiltrate, osteoclastogenesis, and apoptosis of inflammatory cells and fibroblasts. The results of our studies suggest that SFRP1 may be involved in the development of periodontitis, since inhibiting SFRP1 resulted in reduced periodontal breakdown. PMID- 17720859 TI - Hemoglobin and LPS act in synergy to amplify the inflammatory response. AB - Vascular disruption and bleeding during periodontitis likely increase the levels of hemoglobin in gingival crevicular fluid. The aim of this study was to investigate the effect of hemoglobin on the inflammatory responses of human macrophages stimulated with lipopolysaccharides (LPS) isolated from periodontopathogens. The production of interleukin-1 beta (IL-1beta), IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha) by macrophages following challenges with Porphyromonas gingivalis and Fusobacterium nucleatum LPS in the presence or absence of human hemoglobin was analyzed by ELISA. The effect of hemoglobin on LPS-binding to macrophages was evaluated with (3)H-LPS. Hemoglobin and LPS from periodontopathogens acted in synergy to stimulate the production of high levels of IL-1beta, IL-6, IL-8, and TNF-alpha by macrophages. Hemoglobin also enhanced LPS-binding to macrophages. This study suggests that hemoglobin contributes to increases in the levels of pro-inflammatory mediators in periodontal sites by acting in synergy with LPS from periodontopathogens, thus favoring the progression of periodontitis. PMID- 17720860 TI - VIP inhibits P. gingivalis LPS-induced IL-18 and IL-18BPa in monocytes. AB - IL-18 is a pro-inflammatory cytokine that is important in the regulation of T cells and is elevated in inflammatory disorders such as periodontal disease. Vasoactive intestinal peptide (VIP) modulates immune responses to the periodontal pathogen Porphyromonas gingivalis (Pg). Our objective was to investigate the effect of Pg LPS on IL-18 and its natural inhibitor, IL-18 binding protein (IL 18BPa), in human monocytes, and the effect of VIP on this system. We demonstrated that Pg LPS induced both IL-18 and IL-18BPa secretion in cultures of the human monocytic cell line THP-1, as measured by specific ELISA. The addition of antibodies to IL-18BPa to the stimulated THP-1 cultures resulted in increased levels of free IL-18, indicating a specific interaction between IL18 and IL-18BPa in this system. VIP (10(-8)M) inhibited both IL-18 and IL-18Bpa secretion by stimulated monocytes. We conclude that IL-18 and IL-18BPa secretion by monocytes is part of the immune response to Pg, and that VIP can inhibit this process. PMID- 17720862 TI - Inorganic polyphosphate: a possible stimulant of bone formation. AB - Inorganic polyphosphates [Poly(P)] are often distributed in osteoblasts. We undertook the present study to verify the hypothesis that Poly(P) stimulates osteoblasts and facilitates bone formation. The osteoblast-like cell line MC 3T3 E1 was cultured with Poly(P), and gene expression and potential mineralization were evaluated by reverse-transcription polymerase chain-reaction. Alkaline phosphatase activity, von Kossa staining, and resorption pit formation analyses were also determined. The potential role of Poly(P) in bone formation was assessed in a rat alveolar bone regeneration model. Poly(P) induced osteopontin, osteocalcin, collagen 1alpha, and osteoprotegerin expression and increased alkaline phosphatase activity in MC 3T3-E1 cells. Dentin slice pit formation decreased with mouse osteoblast and bone marrow macrophage co-cultivation in the presence of Poly(P). Promotion of alveolar bone regeneration was observed locally in Poly(P)-treated rats. These findings suggest that Poly(P) plays a role in osteoblastic differentiation, activation, and bone mineralization. Thus, local poly(P) delivery may have a therapeutic benefit in periodontal disease. PMID- 17720861 TI - Apoptosis in gingival overgrowth tissues. AB - Variations in the balance between cell proliferation and apoptosis could contribute to the etiology of gingival overgrowth. The aim of this study was to test the hypothesis that, in fibrotic gingival lesions, fibroblast proliferation is stimulated and apoptosis is decreased. Apoptotic index, caspase 3 expression, the proliferative index, FOXO1 expression, and histological inflammation were measured in situ. Analysis of data showed that apoptosis decreased in all forms of gingival overgrowth examined (p < 0.05), and inflammation caused a small but significant increase compared with non-inflamed tissues (p < 0.05). The greatest decrease of apoptosis occurred in the most fibrotic tissues. Cell proliferation was elevated in all forms of gingival overgrowth tested, independent of inflammation (p < 0.05). To identify potential mechanisms of transcriptional regulation of apoptosis, we assessed FOXO1 and caspase 3 expression levels and found them to correlate well with diminished apoptosis. Analysis of data suggests that increased fibroblast proliferation and a simultaneous decrease in apoptosis contribute to gingival overgrowth. PMID- 17720863 TI - Eugenol inhibits K+ currents in trigeminal ganglion neurons. AB - Eugenol, a natural capsaicin congener, is widely used in dentistry. Eugenol inhibits voltage-activated Na(+) and Ca(2+) channels in a transient receptor potential vanilloid 1 (TRPV1)-independent manner. We hypothesized that eugenol also inhibits voltage-gated K(+) currents, and investigated this in rat trigeminal ganglion neurons and in a heterologous system using whole-cell patch clamping. Eugenol inhibited voltage-gated K(+) currents, and the inhibitory effects of eugenol were observed in both capsaicin-sensitive and capsaicin insensitive neurons. Pre-treatment with capsazepine, a well-known antagonist of TRPV1, failed to block the inhibitory effects of eugenol on K(+) currents, suggesting no involvement of TRPV1. Eugenol inhibited human Kv1.5 currents stably expressed in Ltk(-) cells, where TRPV1 is not endogenously expressed. We conclude that eugenol inhibits voltage-gated K(+) currents in a TRPV1-independent manner. The inhibition of voltage-gated K(+) currents is likely to contribute to the irritable action of eugenol. ABBREVIATIONS: human Kv1.5 channel, hKv1.5; transient receptor potential vanilloid 1, TRPV1. PMID- 17720864 TI - Hypoxia induces expression and activation of AMPK in rat dental pulp cells. AB - AMP-activated protein kinase (AMPK) is a stress-responsive enzyme involved in cell adaptation to an energy crisis. We hypothesized that hypoxia suppresses oxidative phosphorylation and ATP production, resulting in AMPK activation to protect cells. We investigated the effects of hypoxia on cell proliferation, the expression of AMPK and hypoxia-inducible factor 1alpha (HIF-1alpha), the activation of AMPK, and the relationship between AMPK and HIF-1alpha expression in rat dental pulp RPC-C2A cells. AMPK in the cells was composed of catalytic alpha1, and regulatory beta1 and gamma1 subunit isoforms. Cell proliferation was initially suppressed under hypoxia, but it increased thereafter, together with an increase in the expression of AMPK and HIF-1alpha, and the activation of AMPK. Down-regulation of AMPKalpha1 by siRNA inhibited cell proliferation under both normoxia and hypoxia, revealing that AMPK induction and activation were required for cell proliferation, although HIF-1alpha expression under hypoxia was not affected. PMID- 17720865 TI - Peritubular dentin lacks piezoelectricity. AB - Dentin is a mesenchymal tissue, and, as such, is based on a collagenous matrix that is reinforced by apatite mineral. Collagen fibrils show piezoelectricity, a phenomenon that is used by piezoresponse force microscopy (PFM) to obtain high resolution images. We applied PFM to image human dentin with 10-nm resolution, and to test the hypothesis that zones of piezoactivity, indicating the presence of collagen fibrils, can be distinguished in dentin. Piezoelectricity was observed by PFM in the dentin intertubular matrix, while the peritubular dentin remained without response. High-resolution imaging of chemically treated intertubular dentin attributed the piezoelectric effect to individual collagen fibrils that differed in the signal strength, depending on the fibril orientation. This study supports the hypothesis that peritubular dentin is a non collagenous tissue and is thus an exception among mineralized tissues that derive from the mesenchyme. PMID- 17720867 TI - UV-B promotes rapid nuclear translocation of the Arabidopsis UV-B specific signaling component UVR8 and activates its function in the nucleus. AB - Arabidopsis thaliana UV RESISTANCE LOCUS8 (UVR8) is a UV-B-specific signaling component that binds to chromatin and regulates UV protection by orchestrating expression of a range of genes. Here, we studied how UV-B regulates UVR8. We show that UV-B stimulates the nuclear accumulation of both a green fluorescent protein (GFP)-UVR8 fusion and native UVR8. Nuclear accumulation leads to UV-B induction of the HY5 gene, encoding a key transcriptional effector of the UVR8 pathway. Nuclear accumulation of UVR8 is specific to UV-B, occurs at low fluence rates, and is observed within 5 min of UV-B exposure. Attachment of a nuclear export signal (NES) to GFP-UVR8 causes cytosolic localization in the absence of UV-B. However, UV-B promotes rapid nuclear accumulation of NES-GFP-UVR8, indicating a concerted mechanism for nuclear translocation. UVR8 lacking the N-terminal 23 amino acids is impaired in nuclear translocation. Attachment of a nuclear localization signal (NLS) to UVR8 causes constitutive nuclear localization. However, NLS-GFP-UVR8 only confers HY5 gene expression following UV-B illumination, indicating that nuclear localization, although necessary for UVR8 function, is insufficient to cause expression of target genes; UV-B is additionally required to stimulate UVR8 function in the nucleus. These findings provide new insights into the mechanisms through which UV-B regulates gene expression in plants. PMID- 17720868 TI - Large-scale, lineage-specific expansion of a bric-a-brac/tramtrack/broad complex ubiquitin-ligase gene family in rice. AB - Selective ubiquitination of proteins is directed by diverse families of ubiquitin protein ligases (or E3s) in plants. One important type uses Cullin-3 as a scaffold to assemble multisubunit E3 complexes containing one of a multitude of bric-a-brac/tramtrack/broad complex (BTB) proteins that function as substrate recognition factors. We previously described the 80-member BTB gene superfamily in Arabidopsis thaliana. Here, we describe the complete BTB superfamily in rice (Oryza sativa spp japonica cv Nipponbare) that contains 149 BTB domain-encoding genes and 43 putative pseudogenes. Amino acid sequence comparisons of the rice and Arabidopsis superfamilies revealed a near equal repertoire of putative substrate recognition module types. However, phylogenetic comparisons detected numerous gene duplication and/or loss events since the rice and Arabidopsis BTB lineages split, suggesting possible functional specialization within individual BTB families. In particular, a major expansion and diversification of a subset of BTB proteins containing Meprin and TRAF homology (MATH) substrate recognition sites was evident in rice and other monocots that likely occurred following the monocot/dicot split. The MATH domain of a subset appears to have evolved significantly faster than those in a smaller core subset that predates flowering plants, suggesting that the substrate recognition module in many monocot MATH-BTB E3s are diversifying to ubiquitinate a set of substrates that are themselves rapidly changing. Intriguing possibilities include pathogen proteins attempting to avoid inactivation by the monocot host. PMID- 17720869 TI - Two Arabidopsis phragmoplast-associated kinesins play a critical role in cytokinesis during male gametogenesis. AB - In plant cells, cytokinesis is brought about by the phragmoplast. The phragmoplast has a dynamic microtubule array of two mirrored sets of microtubules, which are aligned perpendicularly to the division plane with their plus ends located at the division site. It is not well understood how the phragmoplast microtubule array is organized. In Arabidopsis thaliana, two homologous microtubule motor kinesins, PAKRP1/Kinesin-12A and PAKRP1L/Kinesin 12B, localize exclusively at the juxtaposing plus ends of the antiparallel microtubules in the middle region of the phragmoplast. When either kinesin was knocked out by T-DNA insertions, mutant plants did not show a noticeable defect. However, in the absence of both kinesins, postmeiotic development of the male gametophyte was severely inhibited. In dividing microspores of the double mutant, microtubules often became disorganized following chromatid segregation and failed to form an antiparallel microtubule array between reforming nuclei. Consequently, the first postmeiotic cytokinesis was abolished without the formation of a cell plate, which led to failures in the birth of the generative cell and, subsequently, the sperm. Thus, our results indicate that Kinesin-12A and Kinesin 12B jointly play a critical role in the organization of phragmoplast microtubules during cytokinesis in the microspore that is essential for cell plate formation. Furthermore, we conclude that Kinesin-12 members serve as dynamic linkers of the plus ends of antiparallel microtubules in the phragmoplast. PMID- 17720870 TI - Overexpression of human Hsp27 inhibits serum-induced proliferation in airway smooth muscle myocytes and confers resistance to hydrogen peroxide cytotoxicity. AB - Airway smooth muscle (ASM) hypertrophy and hyperplasia are characteristics of asthma that lead to thickening of the airway wall and obstruction of airflow. Very little is known about mechanisms underlying ASM remodeling, but in vascular smooth muscle, it is known that progression of atherosclerosis depends on the balance of myocyte proliferation and cell death. Small heat shock protein 27 (Hsp27) is antiapoptotic in nonmuscle cells, but its role in ASM cell survival is unknown. Our hypothesis was that phosphorylation of Hsp27 may regulate airway remodeling by modifying proliferation, cell survival, or both. To test this hypothesis, adenoviral vectors were used to overexpress human Hsp27 in ASM cells. Cells were infected with empty vector (Ad5) or wild-type Hsp27 (AdHsp27 WT), and proliferation and death were assessed. Overexpressing Hsp27 WT caused a 50% reduction in serum-induced proliferation and increased cell survival after exposure to 100 microM hydrogen peroxide (H(2)O(2)) compared with mock-infected controls. Overexpression studies utilizing an S15A, S78A, and S82A non phosphorylation mutant (AdHsp27 3A) and an S15D, S78D, and S82D pseudo phosphorylation mutant (AdHsp27 3D) showed phosphorylation of Hsp27 was necessary for regulation of ASM proliferation, but not survival. Hsp27 provided protection against H(2)O(2)-induced cytotoxicity by upregulating cellular glutathione levels and preventing necrotic cell death, but not apoptotic cell death. The results support the notion that ASM cells can be stimulated to undergo proliferation and death and that Hsp27 may regulate these processes, thereby contributing to airway remodeling in asthmatics. PMID- 17720871 TI - Congenital NOS2 deficiency prevents impairment of hypoxic pulmonary vasoconstriction in murine ventilator-induced lung injury. AB - Hypoxic pulmonary vasoconstriction (HPV) preserves systemic arterial oxygenation during lung injury by diverting blood flow away from poorly ventilated lung regions. Ventilator-induced lung injury (VILI) is characterized by pulmonary inflammation, lung edema, and impaired HPV leading to systemic hypoxemia. Studying mice congenitally deficient in inducible nitric oxide synthase (NOS2) and wild-type mice treated with a selective NOS2 inhibitor, L-N(6)-(1 iminoethyl)lysine (L-NIL), we investigated the contribution of NOS2 to the impairment of HPV in anesthetized mice subjected to 6 h of either high tidal volume (HV(T)) or low tidal volume (LV(T)) ventilation. HPV was estimated by measuring the changes of left lung pulmonary vascular resistance (LPVR) in response to left mainstem bronchus occlusion (LMBO). LMBO increased the LPVR similarly in wild-type, NOS2(-/-), and wild-type mice treated with L-NIL 30 min before commencing 6 h of LV(T) ventilation (96% +/- 30%, 103% +/- 33%, and 80% +/ 16%, respectively, means +/- SD). HPV was impaired in wild-type mice subjected to 6 h of HV(T) ventilation (23% +/- 16%). In contrast, HPV was preserved after 6 h of HV(T) ventilation in NOS2(-/-) and wild-type mice treated with L-NIL either 30 min before or 6 h after commencing HV(T) ventilation (66% +/- 22%, 82% +/- 29%, and 85% +/- 16%, respectively). After 6 h of HV(T) ventilation and LMBO, systemic arterial oxygen tension was higher in NOS2(-/-) than in wild-type mice (192 +/- 11 vs. 171 +/- 17 mmHg; P < 0.05). We conclude that either congenital NOS2 deficiency or selective inhibition of NOS2 protects mice from the impairment of HPV occurring after 6 h of HV(T) ventilation. PMID- 17720872 TI - Impact of neutrophils on antiviral activity of human bronchoalveolar lavage fluid. AB - Surfactant protein D (SP-D) and neutrophils participate in the early innate immune response to influenza A virus (IAV) infection. SP-D increases neutrophil uptake of IAV and modulates neutrophil respiratory burst responses to IAV; however, neutrophil proteases have been shown to degrade SP-D, and human neutrophil peptide defensins bind to SP-D and can cause precipitation of SP-D from bronchoalveolar lavage fluid (BALF). BALF has significant antiviral activity against IAV. We first added neutrophils to BALF during incubation with IAV. Addition of neutrophils to BALF caused significantly greater clearance of IAV from culture supernatants than from BALF alone, and this effect was significantly more pronounced when neutrophils were activated during incubation with the virus. In contrast, if activated neutrophils were incubated with BALF before addition of virus, they reduced antiviral activity of BALF. This effect correlated with depletion of SP-D from BALF. Activation of neutrophils with agonists that induce primary granule release (including release of human neutrophil peptide defensins) caused SP-D depletion, but activation with PMA, which causes only secondary granule release, did not. The ability of activated neutrophils to deplete SP-D from BALF was partially, but not fully, corrected with protease inhibitors but was unaffected by inhibition of neutrophil respiratory burst responses. These results suggest that chronic neutrophilic inflammation (e.g., as in chronic smoking or cystic fibrosis) may reduce SP-D levels and predispose to IAV infection. In contrast, acute inflammation, as occurs in the early phase of IAV infection, may promote neutrophil-mediated viral clearance. PMID- 17720873 TI - Poly(ADP-ribose) polymerase-1 regulates vimentin expression in lung cancer cells. AB - Vimentin is one of the mammalian intermediate filament proteins. It is expressed in cells of mesenchymal origin and is characteristic of proliferating cells at the fetal stage. During malignancy, vimentin expression is activated in certain lung epithelial cells. Examination of a group of lung cancer cells showed a marked difference in their vimentin expression. The difference in vimentin expression among lung cancer cells is due to differential regulation at the transcriptional level. Analysis of the vimentin promoter revealed a 102-bp promoter sequence that is important for promoter activity in a lung cancer cell line in which vimentin is strongly expressed. This promoter region interacts with poly(ADP-ribose) polymerase-1 (PARP-1), which is also a transcription regulator. Exogenous expression of PARP-1 increased vimentin promoter activity. A shortened PARP-1 without the COOH-terminal catalytic domain showed the same promoter activation effect. Treatment of cells with H(2)O(2) reduced PARP-1 and vimentin expression at the protein level. H(2)O(2) also dose dependently suppressed vimentin promoter activity in cells overexpressing PARP-1. These results demonstrate that vimentin expression in lung cancer cells is regulated at the transcriptional level and that PARP-1 binds and activates the vimentin promoter independent of its catalytic domain and may play a role in H(2)O(2)-induced inhibition of vimentin expression. PMID- 17720874 TI - Perinatal hypoxia triggers alterations in K+ channels of adult pulmonary artery smooth muscle cells. AB - Adverse events during the perinatal period, like hypoxia, have been associated with adult diseases. In pulmonary vessels, K(+) channels play an important role in the regulation of vascular tone. In the fetus, Ca(2+)-activated K(+) channels (K(Ca)) are predominant, whereas from birth voltage-gated K(+) channels (K(V)) prevail in the adult. We postulated that perinatal hypoxia could alter this maturational shift and influence regulation of pulmonary vascular tone in relation to K(+) channels in adulthood. We evaluated the effects of perinatal hypoxia on K(V) and K(Ca) channels in the adult main pulmonary artery (PA) using a murine model. Electrophysiological measurements showed a greater outward current in PA smooth muscle cells of mice born in hypoxia than in controls. In controls, only K(V) channels contributed to this current, whereas in mice born in hypoxia both K(V) and K(Ca) channels were implicated. K(V) channel activity was even higher in mice born in hypoxia than in controls. Therefore, perinatal hypoxia results in increased K(Ca) and K(V) channel activity in adult PA. Moreover, PA of adults born in hypoxia displayed higher large-conductance K(Ca) alpha-subunit and K(V)1.5 alpha-subunit protein expression than controls. Interestingly, relaxation induced by nitric oxide (NO) donors [S-nitroso-N-acetyl D,l-penicillamine, 2-(N,N-diethylamino)-diazenolate-2-oxide] in isolated PA of control mice was not mediated by K(Ca) channels and only slightly by K(V) channels, whereas following perinatal hypoxia both K(Ca) and K(V) channels contributed to this relaxation. Thus perinatal hypoxia results in altered expression and activity of different K(+) channels in the adult main PA, which could contribute to modifications of pulmonary vasoreactivity. PMID- 17720875 TI - Comprehensive gene expression profiling of rat lung reveals distinct acute and chronic responses to cigarette smoke inhalation. AB - Chronic obstructive pulmonary disease (COPD) is a smoking-related disease that lacks effective therapies due partly to the poor understanding of disease pathogenesis. The aim of this study was to identify molecular pathways that could be responsible for the damaging consequences of smoking. To do this, we employed Gene Set Enrichment Analysis to analyze differences in global gene expression, which we then related to the pathological changes induced by cigarette smoke (CS). Sprague-Dawley rats were exposed to whole body CS for 1 day and for various periods up to 8 mo. Gene Set Enrichment Analysis of microarray data identified that metabolic processes were most significantly increased early in the response to CS. Gene sets involved in stress response and inflammation were also upregulated. CS exposure increased neutrophil chemokines, cytokines, and proteases (MMP-12) linked to the pathogenesis of COPD. After a transient acute response, the CS-exposed rats developed a distinct molecular signature after 2 wk, which was followed by the chronic phase of the response. During this phase, gene sets related to immunity and defense progressively increased and predominated at the later time points in smoke-exposed rats. Chronic CS inhalation recapitulated many of the phenotypic changes observed in COPD patients including oxidative damage to macrophages, a slowly resolving inflammation, epithelial damage, mucus hypersecretion, airway fibrosis, and emphysema. As such, it appears that metabolic pathways are central to dealing with the stress of CS exposure; however, over time, inflammation and stress response gene sets become the most significantly affected in the chronic response to CS. PMID- 17720876 TI - Feedlot dust stimulation of interleukin-6 and -8 requires protein kinase Cepsilon in human bronchial epithelial cells. AB - Individuals exposed to dusts from concentrated animal feeding operations report increased numbers of respiratory tract symptoms, and bronchoalveolar lavage samples from such individuals demonstrate elevated lung inflammatory mediators, including interleukin (IL)-8 and IL-6. We previously found that exposure of bronchial epithelial cells to hog barn dusts resulted in a protein kinase C (PKC) dependent increase in IL-6 and IL-8 release. We hypothesized that cattle feedlot dusts would also generate bronchial epithelial interleukin release in vitro. To test this, we used interleukin ELISAs and direct PKC isoform assays. We found that a dust extract from cattle feedlots [feedlot dust extract (FLDE)] augments PKC activity of human bronchial epithelial cells in vitro. A 5-10% dilution of FLDE stimulated a significant release of IL-6 and IL-8 at 6-24 h in a PKC dependent manner vs. control medium-treated cells. An increase in PKCalpha activity was observed with 1 h of FLDE treatment, and PKCepsilon activity was elevated at 6 h of FLDE exposure. The PKCalpha inhibitor, Go-6976, did not inhibit FLDE-stimulated IL-8 and IL-6 release. However, the PKCepsilon inhibitor, Ro 31-8220, effectively inhibited FLDE-stimulated IL-8 and IL-6 release. Inhibition of FLDE-stimulated IL-6 and IL-8 was confirmed in a dominant-negative PKCepsilon-expressing BEAS-2B cell line but not observed in a PKCalpha dominant negative BEAS-2B cell line. These data support the hypothesis that FLDE exposure stimulates bronchial epithelial IL-8 and IL-6 release via a PKCepsilon-dependent pathway. PMID- 17720877 TI - Cigarette smoke irreversibly modifies glutathione in airway epithelial cells. AB - In patients with chronic obstructive pulmonary disease (COPD), an imbalance between oxidants and antioxidants is acknowledged to result in disease development and progression. Cigarette smoke (CS) is known to deplete total glutathione (GSH + GSSG) in the airways. We hypothesized that components in the gaseous phase of CS may irreversibly react with GSH to form GSH derivatives that cannot be reduced (GSX), thereby causing this depletion. To understand this phenomenon, we investigated the effect of CS on GSH metabolism and identified the actual GSX compounds. CS and H(2)O(2) (control) deplete reduced GSH in solution [Delta = -54.1 +/- 1.7 microM (P < 0.01) and -39.8 +/- 0.9 microM (P < 0.01), respectively]. However, a significant decrease of GSH + GSSG was observed after CS (Delta = -75.1 +/- 7.6 microM, P < 0.01), but not after H(2)O(2). Exposure of A549 cells and primary bronchial epithelial cells to CS decreased free sulfhydryl (-SH) groups (Delta = -64.2 +/- 14.6 microM/mg protein, P < 0.05) and irreversibly modified GSH + GSSG (Delta = -17.7 +/- 1.9 microM, P < 0.01) compared with nonexposed cells or H(2)O(2) control. Mass spectrometry (MS) showed that GSH was modified to glutathione-aldehyde derivatives. Further MS identification showed that GSH was bound to acrolein and crotonaldehyde and another, yet to be identified, structure. Our data show that CS does not oxidize GSH to GSSG but, rather, reacts to nonreducible glutathione-aldehyde derivatives, thereby depleting the total available GSH pool. PMID- 17720878 TI - Phosphorothioate cap analogs stabilize mRNA and increase translational efficiency in mammalian cells. AB - Capped RNAs synthesized by in vitro transcription have found wide utility for studying mRNA function and metabolism and for producing proteins of interest. We characterize here a recently synthesized series of cap analogs with improved properties that contain a sulfur substitution for a nonbridging oxygen in either the alpha-, beta-, or gamma-phosphate moieties, m(2) (7,2'-O )Gppp(S)G, m(2) (7,2'-O )Gpp(S)pG, and m(2) (7,2'-O )Gp(S)ppG, respectively. The new compounds were also modified at the 2'-O position of the m(7)Guo to make them anti-reverse cap analogs (ARCAs), i.e., they are incorporated exclusively in the correct orientation during in vitro transcription. Each of the S-ARCAs exists in two diastereoisomeric forms (D1 and D2) that can be resolved by reverse-phase HPLC. A major in vivo pathway for mRNA degradation is initiated by removal of the cap by the pyrophosphatase Dcp1/Dcp2, which cleaves between the alpha- and beta phosphates. Oligonucleotides capped with m(2) (7,2'-O )Gpp(S)pG (D2) were completely resistant to hydrolysis by recombinant human Dcp2 in vitro, whereas those capped with m(2) (7,2'-O )Gpp(S)pG (D1) and both isomers of m(2) (7,2'-O )Gppp(S)G were partially resistant. Luciferase mRNA capped with m(2) (7,2'-O )Gpp(S)pG (D2) had a t (1/2) of 257 min in cultured HC11 mammary epithelial cells compared with 86 min for m(7)Gp(3)G-capped mRNA. Luciferase mRNAs capped with m(2) (7,2'-O )Gpp(S)pG (D1) and m(2) (7,2'-O )Gpp(S)pG (D2) were translated 2.8 fold and 5.1-fold, respectively, more efficiently in HC11 cells than those capped with m(7)Gp(3)G. The greater yield of protein due to combining higher translational efficiency with longer t (1/2) of mRNA should benefit applications that utilize RNA transfection such as protein production, anti-cancer immunization, and gene therapy. PMID- 17720879 TI - A novel monoclonal antibody against human Argonaute proteins reveals unexpected characteristics of miRNAs in human blood cells. AB - Argonaute (Ago) proteins bind to microRNA (miRNAs) and short interfering RNAs (siRNAs) and form the core components of effector complexes that mediate miRNA and siRNA function. Currently, there is a paucity of reliable antibodies against mammalian Ago proteins, thus precluding studies of endogenous Ago proteins from tissues. Here we report the development of 2A8, a novel anti-Ago monoclonal antibody that recognizes human and mouse Ago proteins and efficiently immunoprecipitates miRNAs. We report the characterization of 2A8 and its use to clone miRNAs from human brain and from preparations of human polymorphonuclear leukocytes (neutrophils), which revealed a prevalent miRNA with unusual features. PMID- 17720880 TI - Modulation of individual steps in group I intron catalysis by a peripheral metal ion. AB - Enzymes are complex macromolecules that catalyze chemical reactions at their active sites. Important information about catalytic interactions is commonly gathered by perturbation or mutation of active site residues that directly contact substrates. However, active sites are engaged in intricate networks of interactions within the overall structure of the macromolecule, and there is a growing body of evidence about the importance of peripheral interactions in the precise structural organization of the active site. Here, we use functional studies, in conjunction with published structural information, to determine the effect of perturbation of a peripheral metal ion binding site on catalysis in a well-characterized catalytic RNA, the Tetrahymena thermophila group I ribozyme. We perturbed the metal ion binding site by site-specifically introducing a phosphorothioate substitution in the ribozyme's backbone, replacing the native ligands (the pro-R (P) oxygen atoms at positions 307 and 308) with sulfur atoms. Our data reveal that these perturbations affect several reaction steps, including the chemical step, despite the absence of direct contacts of this metal ion with the atoms involved in the chemical transformation. As structural probing with hydroxyl radicals did not reveal significant change in the three-dimensional structure upon phosphorothioate substitution, the effects are likely transmitted through local, rather subtle conformational rearrangements. Addition of Cd(2+), a thiophilic metal ion, rescues some reaction steps but has deleterious effects on other steps. These results suggest that native interactions in the active site may have been aligned by the naturally occurring peripheral residues and interactions to optimize the overall catalytic cycle. PMID- 17720881 TI - Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib, and dasatinib reveal novel kinase and nonkinase targets. AB - The BCR-ABL tyrosine kinase inhibitor imatinib represents the current frontline therapy in chronic myeloid leukemia. Because many patients develop imatinib resistance, 2 second-generation drugs, nilotinib and dasatinib, displaying increased potency against BCR-ABL were developed. To predict potential side effects and novel medical uses, we generated comprehensive drug-protein interaction profiles by chemical proteomics for all 3 drugs. Our studies yielded 4 major findings: (1) The interaction profiles of the 3 drugs displayed strong differences and only a small overlap covering the ABL kinases. (2) Dasatinib bound in excess of 30 Tyr and Ser/Thr kinases, including major regulators of the immune system, suggesting that dasatinib might have a particular impact on immune function. (3) Despite the high specificity of nilotinib, the receptor tyrosine kinase DDR1 was identified and validated as an additional major target. (4) The oxidoreductase NQO2 was bound and inhibited by imatinib and nilotinib at physiologically relevant drug concentrations, representing the first nonkinase target of these drugs. PMID- 17720883 TI - Submicroscopic bone marrow involvement in isolated extramedullary relapses in childhood acute lymphoblastic leukemia: a more precise definition of "isolated" and its possible clinical implications, a collaborative study of the Resistant Disease Committee of the International BFM study group. AB - This study investigates the extent of bone marrow (BM) involvement at diagnosis of apparent isolated extramedullary (AIEM) relapses of childhood acute lymphoblastic leukemia (ALL) and its relation to prognosis. Sixty-four children with first AIEM relapse treated in Germany, Czech Republic, or France were included. Real-time quantitative polymerase chain reaction using T-cell receptor and immunoglobulin gene rearrangements provided a sensitive measure of submicroscopic BM involvement, which was detectable at a level of 10(-4) or higher in 46 patients and less than 10(-4) in 11 patients, and was nondetectable (sensitivity: 10(-4)) in 7 patients. In the total cohort, the probability of event-free survival (pEFS) for children with BM involvement of 10(-4) or higher was 0.30 (0.09 +/- SE) versus 0.60 (+/- 0.12) for those with less than 10(-4) (P = .13). The cumulative incidence of subsequent relapse was 0.24 (+/- 0.01) for patients with BM involvement less than 10(-4) and 0.65 (+/- 0.01) for those with 10(-4) or higher (P = .012). Restricted to central nervous system (CNS) relapses, pEFS was 0.11 (+/- 0.09) for patients with BM involvement 10(-4) or higher and 0.63 (+/- 0.17) for those with less than 10(-4) (P = .053). CNS relapses were associated with a higher (> or = 10(-4): 80%) submicroscopic BM involvement than testicular relapses (> or = 10(-4): 57%, P = .08). In summary, we show marked heterogeneity of submicroscopic BM involvement at first AIEM relapse diagnosis in children with ALL, and demonstrate its possible prognostic relevance. PMID- 17720882 TI - Proapoptotic BH3-only protein Bim is essential for developmentally programmed death of germinal center-derived memory B cells and antibody-forming cells. AB - T cell-dependent B-cell immune responses induce germinal centers that are sites for expansion, diversification, and selection of antigen-specific B cells. During the immune response, antigen-specific B cells are removed in a process that favors the retention of cells with improved affinity for antigen, a cell death process inhibited by excess Bcl-2. In this study, we examined the role of the BH3 only protein Bim, an initiator of apoptosis in the Bcl-2-regulated pathway, in the programmed cell death accompanying an immune response. After immunization, Bim-deficient mice showed persistence of both memory B cells lacking affinity enhancing mutations in their immunoglobulin genes and antibody-forming cells secreting low-affinity antibodies. This was accompanied by enhanced survival of both cell types in culture. We have identified for the first time the physiologic mechanisms for killing low-affinity antibody-expressing B cells in an immune response and have shown this to be dependent on the BH3-only protein Bim. PMID- 17720884 TI - Down-regulation of the TGF-beta target gene, PTPRK, by the Epstein-Barr virus encoded EBNA1 contributes to the growth and survival of Hodgkin lymphoma cells. AB - The Epstein-Barr virus (EBV) contributes to the growth and survival of Hodgkin lymphoma (HL) cells. Here we report that down-regulation of the transforming growth factor-beta (TGF-beta) target gene, protein tyrosine phosphatase receptor kappa (PTPRK), followed EBV infection of HL cells and was also more frequently observed in the Hodgkin and Reed-Sternberg (HRS) cells of EBV-positive compared with EBV-negative primary HL. The viability and proliferation of EBV-positive HL cells was decreased by overexpression of PTPRK, but increased following the knockdown of PTPRK expression in EBV-negative HL cells, demonstrating that PTPRK is a functional tumor suppressor in HL. EBV suppressed the TGF-beta-mediated activation of PTPRK expression, suggesting disruption of TGF-beta signaling upstream of PTPRK. This was confirmed when we showed that the Epstein-Barr nuclear antigen-1 (EBNA1) decreased Smad2 protein levels and that this was responsible for PTPRK down-regulation. EBNA1 decreased the half-life of Smad2 but did not interact with Smad2. By down-regulating Smad2 protein expression, EBNA1 apparently disables TGF-beta signaling, which subsequently decreases transcription of the PTPRK tumor suppressor. We speculate that loss of the phosphatase function of PTPRK may activate as-yet-unidentified growth-promoting protein tyrosine kinases, which in turn contribute to the pathogenesis of EBV positive HL. PMID- 17720885 TI - Activity-dependent neuroprotective protein snippet NAP reduces tau hyperphosphorylation and enhances learning in a novel transgenic mouse model. AB - Activity-dependent neuroprotective protein (ADNP) differentially interacts with chromatin to regulate essential genes. Because complete ADNP deficiency is embryonic lethal, the outcome of partial ADNP deficiency was examined. ADNP(+/-) mice exhibited cognitive deficits, significant increases in phosphorylated tau, tangle-like structures, and neurodegeneration compared with ADNP(+/+) mice. Increased tau hyperphosphorylation is known to cause memory impairments in neurodegenerative diseases associated with tauopathies, including the most prevalent Alzheimer's disease. The current results suggest that ADNP is an essential protein for brain function and plays a role in normal cognitive performance. ADNP-deficient mice offer an ideal paradigm for evaluation of cognitive enhancers. NAP (NAPVSIPQ) is a peptide derived from ADNP that interacts with microtubules and provides potent neuroprotection. NAP treatment partially ameliorated cognitive deficits and reduced tau hyperphosphorylation in the ADNP(+/-) mice. NAP is currently in phase II clinical trials assessing effects on mild cognitive impairment. PMID- 17720886 TI - A select set of opioid ligands induce up-regulation by promoting the maturation and stability of the rat kappa-opioid receptor in human embryonic kidney 293 cells. AB - Ligand-induced regulation of the rat kappa-opioid receptor (rKOR) was investigated in human embryonic kidney 293 cells stably expressing the FLAG tagged rKOR. Incubation of rKOR cells with naltrexone for 24 h increased the B(max) >3-fold, with no change in the affinity of [(3)H]diprenorphine. Two immunoreactive receptor species were present in cell lysates: naltrexone treatment caused a >3-fold increase in the 52-kDa species while decreasing the level of the 42-kDa species. Dynorphin(1-13), U69,593 [(5alpha,7alpha,8beta)-(+) N-methyl-N-(7-[1-pyrrolidinyl]-1-oxaspiro[4,5]dec-8-yl)benzeneacetamide], or salvinorin A [2S,4aR,6aR,7R,9S,10aS, 10bR)-9-(acetyloxy)-2-(3-furanyl)dodecahydro 6a,10b-dimethyl-4,10-dioxo-2H-naphtho[2,1c]pyran-7-carboxylic acid methyl ester] treatment did not alter the level of immunoreactive rKOR protein, whereas etorphine, cyclazocine, naloxone, and naloxone methiodide increased the 52-kDa and decreased the 42-kDa rKOR bands. Receptor up-regulation was associated with an increase in the number of cell surface receptors and a 2-fold increase in the E(max) for guanosine 5'-O-(3-[(35)S]thio)triphosphate binding. Glycosidase digestion indicated that the 52- and 42-kDa receptors contained complex and high mannose N-glycans, respectively, Pulse-chase analysis and glycosidase digestion sensitivities suggested that the 42-kDa rKOR species was a precursor of the 52 kDa species. Naltrexone did not alter rKOR mRNA levels or translational efficiency, and rKOR up-regulation was not inhibited by cycloheximide. Brefeldin A caused accumulation of intracellular rKOR intermediates, and coincubation with naltrexone increased the levels of the brefeldin-induced species significantly. These results suggest that select opioid ligands up-regulate rKOR by enhancing the rate of receptor folding and maturation and by protecting the receptor from degradation, resulting in an increase in the number of rKOR binding sites, immunoreactive protein, and functional receptors. PMID- 17720887 TI - Biological function of mutant forms of JAGGED1 proteins in Alagille syndrome: inhibitory effect on Notch signaling. AB - Heterozygous mutations in JAGGED1, encoding a single-pass transmembrane ligand for the Notch receptors, cause Alagille syndrome (AGS), a polymalformative disorder affecting the liver, heart, eyes and skeleton and characterized by a peculiar facies. Most of the JAGGED1 mutations generate premature termination codons, and as a result, two pathogenic mechanisms causing AGS have been proposed: haploinsufficiency or a dominant-negative effect of putative truncated proteins. To determine whether missense or protein-truncating mutations in JAGGED1 can lead to the synthesis and function of abnormal proteins, we performed cell culture experiments. We showed that human JAGGED1 undergoes a metalloprotease-dependent cleavage resulting in the shedding of its extracellular domain and that this domain seems able to fulfill a biological function in vitro, probably by antagonizing Notch signaling. Moreover, the soluble form of JAGGED1 was able to compete with the transmembrane ligand. Mutant proteins with missense or nonsense mutations were synthesized and gave rise to a chord-like phenotype and a migration defect when expressed by stably transfected cells. These chord like structures were similar to the phenotype exhibited by fibroblasts isolated from a fetus with a protein-truncating mutation. Results obtained from Notch signaling inhibition and Notch reporter assays showed that this chord-like phenotype, exhibited by mutant JAGGED1 transfectants, may result from an inhibitory effect on Notch signaling. Altogether, our results favor a dominant negative mechanism of some JAGGED1 mutations in AGS. PMID- 17720888 TI - Increased expression of Grainyhead-like-3 rescues spina bifida in a folate resistant mouse model. AB - Neural tube defects (NTDs), such as spina bifida, are common and severe birth defects in humans but the underlying causes are poorly understood. The pathogenesis and etiology of spina bifida in the curly tail mouse closely resemble defects in humans, providing a well-characterized model of NTDs. Grainyhead-like-3 (Grhl3), which encodes a transcription factor, was recently identified as a candidate gene for curly tail based on chromosomal location and the occurrence of spina bifida in Grhl3 null mice. However, the causative curly tail mutation has not been established, while the relationship between Grhl3 gene expression and the known cellular defect leading to NTDs in curly tail is unknown. Spina bifida in curly tail results from a cell type-specific proliferation defect in the hindgut endoderm, and we find that Grhl3 is expressed specifically in this tissue during the final stages of spinal neural tube closure in wild type embryos. Moreover, Grhl3 expression is diminished in the spinal region of neurulation-stage curly tail embryos. Curly tail mice do not carry a coding region mutation in Grhl3, however, we found a putative regulatory mutation upstream of the Grhl3 gene, which may be responsible for the expression deficit. In order to test the hypothesis that spina bifida in curly tail mice results from insufficient expression of Grhl3, we generated Grhl3-expressing curly tail mice by bacterial artificial chromosome-mediated transgenesis and demonstrated complete rescue of spina bifida. This study provides evidence for a critical role of diminished Grhl3 expression in causing spinal NTDs in the curly tail mouse model. PMID- 17720889 TI - New pharmacologic approaches to treating diabetic retinopathy. AB - PURPOSE: The goal of treatment of diabetic retinopathy, limitations of laser photocoagulation, endpoints used in clinical studies of diabetic retinopathy treatments, and the mechanism of action, efficacy, and safety of several new and emerging therapies targeting the biochemical pathways that link chronic hyperglycemia with microvascular damage in patients with diabetic retinopathy are discussed. SUMMARY: Improving or preserving vision is the primary goal of treatment for diabetic retinopathy. Limitations of laser photocoagulation include a lack of efficacy in some cases, discomfort from the procedure, the need for repeated treatment, and a risk of retinal damage and scarring. Visual acuity, quality of life, and macular thickness are used as endpoints in clinical studies of diabetic retinopathy treatments. Microvascular damage in patients with chronic hyperglycemia is mediated by interrelated pathways involving aldose reductase, advanced glycation end products, protein kinase C (PKC), and vascular endothelial growth factor (VEGF). Oral aldose reductase inhibitors have been studied with some success only in patients with diabetic peripheral neuropathy. The oral PKC inhibitor midostaurin and oral selective PKC beta inhibitor ruboxistaurin appear promising for improving or maintaining visual acuity, with gastrointestinal complaints the most commonly reported adverse effects. Intra-vitreal injection of corticosteroids or VEGF inhibitors is associated with short-lived improvement in or maintenance of visual acuity, a need for repeated injection, and a risk of local adverse effects. CONCLUSION: A variety of promising new therapies for diabetic retinopathy targeting the biochemical pathways that cause microvascular damage are under investigation. Additional clinical research is needed to determine the role of these new therapies in treating diabetic retinopathy. PMID- 17720892 TI - Etiology and natural history of diabetic retinopathy: an overview. AB - PURPOSE: The morbidity and mortality from and economic impact of diabetes mellitus in the United States, pathogenesis of microvascular diabetic complications, contribution of poor long-term glycemic control to risk for diabetic retinopathy and other microvascular complications, prevalence of diabetic retinopathy, methods for measuring visual acuity, and manifestations of disease progression and etiology of blindness in patients with diabetic retinopathy are discussed. SUMMARY: Diabetic retinopathy and other microvascular and macrovascular complications of diabetes cause considerable morbidity and mortality and have a large economic impact in the United States. Patients with poor long-term glycemic control are more vulnerable to diabetic retinopathy than to other microvascular complications of diabetes. Diabetic retinopathy is the third leading cause of all cases of blindness in the United States and the leading cause of new cases in adults. Retinopathy is already present at the time of diagnosis in 20% of patients with type 2 diabetes. Retinopathy and other micro vascular complications are attributed to chronic hyperglycemia, vascular damage and leakage, edema, capillary basement membrane thickening, neovascularization, hemorrhage, and ischemia. Measurements of visual acuity loss are expressed in terms of the distance at which a person with normal vision can see what the test subject can see from 20 feet away. Diabetic retinopathy begins as nonproliferative abnormalities and progresses to proliferative diabetic retinopathy. Macular edema can develop at any time in the progression of diabetic retinopathy. Macular ischemia, retinal and vitreous hemorrhage, and retinal detachment are the primary causes of blindness in patients with diabetic retinopathy. CONCLUSION: Diabetic retinopathy is a costly and progressive condition associated with chronic hyperglycemia. It is potentially vision threatening. PMID- 17720893 TI - Screening for and managing diabetic retinopathy: current approaches. AB - PURPOSE: The anatomy of the eye and the pathogenesis, clinical features, and prevalence of vision impairment from diabetic retinopathy are described. Screening and risk factors for and treatment of diabetic retinopathy also are addressed. SUMMARY: The macula and fovea play a critical role in vision. Several interrelated biochemical pathways involving aldose reductase, advanced glycation end products, and protein kinase C link chronic hyperglycemia with retinal capillary endothelial cell damage and dysfunction in patients with diabetic retinopathy. Vision loss and blindness from diabetic retinopathy usually are the result of vascular leakage or ischemia. Screening for retinopathy should be performed within three to five years after the onset of type 1 diabetes and shortly after the diagnosis of type 2 disease, with annual follow-up examinations in both types of diabetes. In patients with diabetic retinopathy, severe vision impairment is less common and less readily corrected than mild vision impairment, and vision impairment is more common and less readily corrected in elderly patients with diabetes than in younger diabetics. Modifiable risk factors for diabetic retinopathy include A1C level, hypertension, cigarette smoking, and dyslipidemia. Tight control of blood glucose concentrations and blood pressure can reduce the risk for and progression of diabetic retinopathy. Aspirin therapy and smoking cessation also are recommended. Dyslipidemia in patients with diabetes is associated with retinopathy progression and vision loss. Treatment of dyslipidemia provides cardiovascular benefits in patients with diabetes, but whether it provides vision benefits remains to be determined. Laser photocoagulation therapy reduces the risk of vision loss in patients with diabetic macular edema, severe nonproliferative diabetic retinopathy, or proliferative diabetic retinopathy. Intraocular surgery may be used for patients with vitreous hemorrhage and retinal detachment of the macula. CONCLUSION: Therapeutic approaches used for patients with or at risk for diabetic retinopathy include drug therapy to reduce modifiable risk factors, laser photocoagulation, and intraocular surgery. Screening plays an important role in early detection and intervention to prevent the progression of diabetic retinopathy. PMID- 17720894 TI - Unlabeled probes for the detection and typing of herpes simplex virus. AB - BACKGROUND: Unlabeled probe detection with a double-stranded DNA (dsDNA) binding dye is one method to detect and confirm target amplification after PCR. Unlabeled probes and amplicon melting have been used to detect small deletions and single nucleotide polymorphisms in assays where template is in abundance. Unlabeled probes have not been applied to low-level target detection, however. METHODS: Herpes simplex virus (HSV) was chosen as a model to compare the unlabeled probe method to an in-house reference assay using dual-labeled, minor groove binding probes. A saturating dsDNA dye (LCGreen Plus) was used for real-time PCR. HSV-1, HSV-2, and an internal control were differentiated by PCR amplicon and unlabeled probe melting analysis after PCR. RESULTS: The unlabeled probe technique displayed 98% concordance with the reference assay for the detection of HSV from a variety of archived clinical samples (n = 182). HSV typing using unlabeled probes was 99% concordant (n = 104) to sequenced clinical samples and allowed for the detection of sequence polymorphisms in the amplicon and under the probe. CONCLUSIONS: Unlabeled probes and amplicon melting can be used to detect and genotype as few as 10 copies of target per reaction, restricted only by stochastic limitations. The use of unlabeled probes provides an attractive alternative to conventional fluorescence-labeled, probe-based assays for genotyping and detection of HSV and might be useful for other low-copy targets where typing is informative. PMID- 17720895 TI - Variants in the Ca V 2.3 (alpha 1E) subunit of voltage-activated Ca2+ channels are associated with insulin resistance and type 2 diabetes in Pima Indians. AB - OBJECTIVE: Linkage to type 2 diabetes has been reported on chromosome 1q21-25 in Pima Indians. Fine mapping identified single nucleotide polymorphisms (SNPs) near the CACNA1E gene associated with this disease. CACNA1E encodes the voltage dependent calcium channel Ca(v)2.3 Ca(2+), and mice lacking this channel exhibit impaired glucose tolerance and insulin secretion. Therefore, CACNA1E was investigated as a positional candidate gene. RESEARCH DESIGN AND METHODS: CACNA1E was sequenced, and 28 SNPs were genotyped in the same group of Pima subjects who had been analyzed in the linkage study. Allele-specific expression was used to functionally evaluate a variant in the 3' untranslated region (UTR). RESULTS: A novel G/A variant in the 3'-UTR was associated with young-onset type 2 diabetes (odds ratio 2.09 per copy of the G-allele [95% CI 1.31-3.33], adjusted P = 0.001) and had an effect on the evidence for linkage at chromosome 1q21-25 (P = 0.004). Among 372 nondiabetic Pima subjects who had undergone metabolic testing, the risk allele was associated with reduced insulin action including increased fasting, 30, 60, and 120 min plasma glucose concentrations and increased fasting plasma insulin during an oral glucose tolerance test (all P < 0.01), as well as a decreased rate of insulin-stimulated glucose disposal at both physiologically and maximally stimulated insulin concentrations (both P < 0.002). Functional analysis of this variant showed that the nonrisk allele had a 2.3-fold higher expression compared with the risk allele. CONCLUSIONS: A functional variant in CACNA1E contributes to type 2 diabetes susceptibility by affecting insulin action. This variant partially explains the linkage to type 2 diabetes on chromosome 1q21-25 in Pima Indians. PMID- 17720896 TI - Protective effects of cyclooxygenase-2 gene inactivation against peripheral nerve dysfunction and intraepidermal nerve fiber loss in experimental diabetes. AB - OBJECTIVE: Activation of the cyclooxygenase (COX) pathway with secondary neurovascular deficits are implicated in the pathogenesis of experimental diabetic peripheral neuropathy (DPN). The aim of this study was to explore the interrelationships between hyperglycemia, activation of the COX-2 pathway, and oxidative stress and inflammation in mediating peripheral nerve dysfunction and whether COX-2 gene inactivation attenuates nerve fiber loss in long-term experimental diabetes. RESEARCH DESIGN AND METHODS: Motor and sensory digital nerve conduction velocities, sciatic nerve indexes of oxidative stress, prostaglandin content, markers of inflammation, and intraepidermal nerve fiber (IENF) density were measured after 6 months in control and diabetic COX-2 deficient (COX-2(-/-)) and littermate wild-type (COX-2(+/+)) mice. The effects of a selective COX-2 inhibitor, celecoxib, on these markers were also investigated in diabetic rats. RESULTS: Under normal conditions, there were no differences in blood glucose, peripheral nerve electrophysiology, markers of oxidative stress, inflammation, and IENF density between COX-2(+/+) and COX-2(-/-) mice. After 6 months, diabetic COX-2(+/+) mice experienced significant deterioration in nerve conduction velocities and IENF density and developed important signs of increased oxidative stress and inflammation compared with nondiabetic mice. Diabetic COX-2( /-) mice were protected against functional and biochemical deficits of experimental DPN and against nerve fiber loss. In diabetic rats, selective COX-2 inhibition replicated this protection. CONCLUSIONS: These data suggest that selective COX-2 inhibition may be useful for preventing or delaying DPN. PMID- 17720897 TI - Hyperinsulinemia rapidly increases human muscle microvascular perfusion but fails to increase muscle insulin clearance: evidence that a saturable process mediates muscle insulin uptake. AB - OBJECTIVE: Transport of insulin from the central circulation into muscle is rate limiting for the stimulation of glucose metabolism. By recruiting muscle microvasculature, insulin may promote its own movement into muscle interstitium. We tested whether in humans, as in the rat, insulin exerts an early action to recruit microvasculature within skeletal muscle. We further hypothesized that expansion of the microvascular volume of muscle would enhance muscle insulin clearance. RESEARCH DESIGN AND METHODS: Microvascular volume, total blood flow, and muscle insulin and glucose uptake (forearm balance method) were measured in 14 lean, healthy volunteers before and during a 2-h hyperinsulinemic-euglycemic clamp (1 mU x kg(-1) x min(-1)). Microvascular volume was measured using contrast enhanced ultrasound. RESULTS: Forearm muscle microvascular volume increased within 20 min of insulin infusion (P < 0.01), whereas an effect to increase total forearm flow was not observed until 100 min. Forearm insulin uptake increased with physiological hyperinsulinemia (15 +/- 3 and 87 +/- 13 fmol x min(-1) x 100 ml(-1) basal vs. last 40 min of clamp, P < 0.001). However, the extraction fraction and clearance of insulin declined (P = 0.02, for each), indicating saturability of muscle insulin uptake at physiological hyperinsulinemia. CONCLUSIONS: Skeletal muscle contributes to peripheral insulin clearance both in the basal state and with physiological hyperinsulinemia. Insulin promptly expands human muscle microvascular volume but only slowly increases blood flow. Despite increased microvascular volume available for insulin uptake, muscle insulin clearance decreases significantly. These findings are consistent with the presence of a saturable transport mechanism facilitating the transendothelial transport of insulin into human muscle. PMID- 17720898 TI - Childhood predictors of young-onset type 2 diabetes. AB - OBJECTIVE: Optimal prevention of young-onset type 2 diabetes requires identification of the early-life modifiable risk factors. We aimed to do this using longitudinal data in 1,604 5- to 19-year-old initially nondiabetic American Indians. RESEARCH DESIGN AND METHODS: For type 2 diabetes prediction, we derived an optimally weighted, continuously distributed, standardized multivariate score (zMS) comprising commonly measured metabolic, anthropometric, and vascular traits (i.e., fasting and 2-h glucose, A1C, BMI, waist circumference, fasting insulin, HDL cholesterol, triglycerides, and blood pressures) and compared the predictive power for each feature against zMS. RESULTS: In separate Cox proportional hazard models, adjusted for age, sex, and ethnicity, zMS and each of its component risk factors were associated with incident type 2 diabetes. Stepwise proportional hazards models selected fasting glucose, 2-h glucose, HDL cholesterol, and BMI as independent diabetes predictors; individually, these were weaker predictors than zMS (P < 0.01). However, a parsimonious summary score combining only these variables had predictive power similar to that of zMS (P = 0.33). Although intrauterine diabetes exposure or parental history of young-onset diabetes increased a child's absolute risk of developing diabetes, the magnitude of the diabetes-risk relationships for zMS and the parsimonious score were similar irrespective of familial risk factors. CONCLUSIONS: We have determined the relative value of the features of the metabolic syndrome in childhood for the prediction of subsequent type 2 diabetes. Our findings suggest that strategies targeting obesity, dysregulated glucose homeostasis, and low HDL cholesterol during childhood and adolescence may have the most success in preventing diabetes. PMID- 17720899 TI - Terminal regions of wheat chromosomes select their pairing partners in meiosis. AB - Many plant species, including important crops like wheat, are polyploids that carry more than two sets of genetically related chromosomes capable of meiotic pairing. To safeguard a diploid-like behavior at meiosis, many polyploids evolved genetic loci that suppress incorrect pairing and recombination of homeologues. The Ph1 locus in wheat was proposed to ensure homologous pairing by controlling the specificity of centromere associations that precede chromosome pairing. Using wheat chromosomes that carry rye centromeres, we show that the centromere associations in early meiosis are not based on homology and that the Ph1 locus has no effect on such associations. Although centromeres indeed undergo a switch from nonhomologous to homologous associations in meiosis, this process is driven by the terminally initiated synapsis. The centromere has no effect on metaphase I chiasmate chromosome associations: homologs with identical or different centromeres, in the presence and absence of Ph1, pair the same. A FISH analysis of the behavior of centromeres and distal chromomeres in telocentric and bi-armed chromosomes demonstrates that it is not the centromeric, but rather the subtelomeric, regions that are involved in the correct partner recognition and selection. PMID- 17720901 TI - Genetic dissection of cytonuclear epistasis in line crosses. AB - Dissection of cytonuclear interactions is fundamentally important for understanding the genetic architecture of complex traits. Here we propose a mating design based on reciprocal crosses and extend the existing QTL mapping method to evaluate the contribution of cytoplasm and QTL x cytoplasm interactions to the phenotypic variation. Efficiency of the design and method is demonstrated via simulated data. PMID- 17720902 TI - Significance thresholds for quantitative trait locus mapping under selective genotyping. AB - In the case of selective genotyping, the usual permutation test to establish statistical significance for quantitative trait locus (QTL) mapping can give inappropriate significance thresholds, especially when the phenotype distribution is skewed. A stratified permutation test should be used, with phenotypes shuffled separately within the genotyped and ungenotyped individuals. PMID- 17720904 TI - A single nucleotide polymorphism in the DNA polymerase gamma gene of Saccharomyces cerevisiae laboratory strains is responsible for increased mitochondrial DNA mutability. AB - In the Saccharomyces cerevisiae strains used for genome sequencing and functional analysis, the mitochondrial DNA replicase Mip1p contains a single nucleotide polymorphism changing the strictly conserved threonine 661 to alanine. This substitution is responsible for the increased rate of mitochondrial DNA point mutations and deletions in these strains. PMID- 17720905 TI - Joint estimation of migration rate and effective population size using the island model. AB - Using the island model of population demography, I report that the demographic parameters migration rate and effective population size can be jointly estimated with equilibrium probabilities of identity in state calculated using a sample of genotypes collected at a single point in time from a single generation. The method, which uses moment-type estimators, applies to dioecious populations in which females and males have identical demography and monoecious populations with no selfing and requires that offspring genotypes are sampled following reproduction and prior to migration. I illustrate the estimation procedure using the infinite-island model with no mutation and the finite-island model with three kinds of mutation models. In the infinite-island model with no mutation, the estimators can be expressed as simple functions of estimates of the F-statistic parameters F(IT) and F(ST). In the finite-island model with mutation among k alleles, mutation rate, migration rate, and effective population size can be simultaneously estimated. The estimates of migration rate and effective population size are somewhat robust to violations in assumptions that may arise in empirical applications such as different kinds of mutation models and deviations from temporal equilibrium. PMID- 17720900 TI - The DrosDel deletion collection: a Drosophila genomewide chromosomal deficiency resource. AB - We describe a second-generation deficiency kit for Drosophila melanogaster composed of molecularly mapped deletions on an isogenic background, covering approximately 77% of the Release 5.1 genome. Using a previously reported collection of FRT-bearing P-element insertions, we have generated 655 new deletions and verified a set of 209 deletion-bearing fly stocks. In addition to deletions, we demonstrate how the P elements may also be used to generate a set of custom inversions and duplications, particularly useful for balancing difficult regions of the genome carrying haplo-insufficient loci. We describe a simple computational resource that facilitates selection of appropriate elements for generating custom deletions. Finally, we provide a computational resource that facilitates selection of other mapped FRT-bearing elements that, when combined with the DrosDel collection, can theoretically generate over half a million precisely mapped deletions. PMID- 17720906 TI - The Flightless I homolog, fli-1, regulates anterior/posterior polarity, asymmetric cell division and ovulation during Caenorhabditis elegans development. AB - Flightless I (Fli I) is an evolutionarily conserved member of the gelsolin family, containing actin-binding and severing activity in vitro. The physiological function of Fli I during animal development remains largely undefined. In this study, we reveal a key role of the Caenorhabditis elegans Fli I homolog, fli-1, in specifying asymmetric cell division and in establishing anterior-posterior polarity in the zygote. The fli-1 gene also regulates the cytokinesis of somatic cells and the development of germline and interacts with the phosphoinositol-signaling pathway in the regulation of ovulation. The fli-1 reporter gene shows that the localization of FLI-1 coincides with actin-rich regions and that the actin cytoskeleton is impaired in many tissues in the fli-1 mutants. Furthermore, the function of fli-1 in C. elegans can be functionally substituted by the Drosophila Fli I. Our studies demonstrate that fli-1 plays an important role in regulating the actin-dependent events during C. elegans development. PMID- 17720908 TI - A hypothesis for how chromosome 11 translocations cause psychiatric disorders. AB - Despite extensive effort for many years, the etiology of major psychiatric diseases remains unknown. A recent study by Baysal et al. has argued against the ALG9 gene variants in causing psychosis. Due to its disruption by a balanced t(9p24;11q23) translocation that segregates with the disorder in a family, it was proposed to be a primary candidate gene causing psychosis. In addition, a recent review article by Pickard et al., entitled "Cytogenetics and gene discovery in psychiatric disorders," highlighted the importance of studies of chromosome rearrangements in finding disease-causing mutations. However, achieving the goal of finding genes by conventional association studies and by investigating chromosome rearrangements remains elusive. Here we discuss a fundamentally different explanation from the usual one considered by workers in the field concerning chromosome aberrations and psychoses etiology. We hypothesize how chromosome aberrations might cause disease but the gene at the rearrangement breakpoint is irrelevant for the etiology. Moreover, we discuss subsequently published findings that help scrutinize validity of the two very different hypotheses considered in the psychiatric genetics field. In sum, we alert the readers to the complexities of interpreting phenotypes associated with rearrangements. PMID- 17720909 TI - Analysis of litter size and average litter weight in pigs using a recursive model. AB - An analysis of litter size and average piglet weight at birth in Landrace and Yorkshire using a standard two-trait mixed model (SMM) and a recursive mixed model (RMM) is presented. The RMM establishes a one-way link from litter size to average piglet weight. It is shown that there is a one-to-one correspondence between the parameters of SMM and RMM and that they generate equivalent likelihoods. As parameterized in this work, the RMM tests for the presence of a recursive relationship between additive genetic values, permanent environmental effects, and specific environmental effects of litter size, on average piglet weight. The equivalent standard mixed model tests whether or not the covariance matrices of the random effects have a diagonal structure. In Landrace, posterior predictive model checking supports a model without any form of recursion or, alternatively, a SMM with diagonal covariance matrices of the three random effects. In Yorkshire, the same criterion favors a model with recursion at the level of specific environmental effects only, or, in terms of the SMM, the association between traits is shown to be exclusively due to an environmental (negative) correlation. It is argued that the choice between a SMM or a RMM should be guided by the availability of software, by ease of interpretation, or by the need to test a particular theory or hypothesis that may best be formulated under one parameterization and not the other. PMID- 17720910 TI - The number of loci that affect milk production traits in dairy cattle. AB - We have used the results of an experiment mapping quantitative trait loci (QTL) affecting milk yield and composition to estimate the total number of QTL affecting these traits. We did this by estimating the number of segregating QTL within a half-sib daughter design using logic similar to that used to estimate the "false discovery rate" (FDR). In a half-sib daughter design with six sire families we estimate that the average sire was heterozygous for approximately 5 QTL per trait. Also, in most cases only one sire was heterozygous for any one QTL; therefore at least 30 QTL were likely to be segregating for these milk production traits in this Holstein population. PMID- 17720907 TI - Molecular evolution of pathogenicity-island genes in Pseudomonas viridiflava. AB - The bacterial pathogen Pseudomonas viridiflava possesses two pathogenicity islands (PAIs) that share many gene homologs, but are structurally and phenotypically differentiated (T-PAI and S-PAI). These PAIs are paralogous, but only one is present in each isolate. While this dual presence/absence polymorphism has been shown to be maintained by balancing selection, little is known about the molecular evolution of individual genes on the PAIs. Here we investigate genetic variation of 12 PAI gene loci (7 on T-PAI and 5 on S-PAI) in 96 worldwide isolates of P. viridiflava. These genes include avirulence genes (hopPsyA and avrE), their putative chaperones (shcA and avrF), and genes encoding the type III outer proteins (hrpA, hrpZ, and hrpW). Average nucleotide diversities in these genes (pi = 0.004-0.020) were close to those in the genetic background. Large numbers of recombination events were found within PAIs and a sign of positive selection was detected in avrE. These results suggest that the PAI genes are evolving relatively freely from each other on the PAIs, rather than as a single unit under balancing selection. Evolutionarily stable PAIs may be preferable in this species because preexisting genetic variation enables P. viridiflava to respond rapidly to natural selection. PMID- 17720913 TI - Derivation of the shrinkage estimates of quantitative trait locus effects. AB - The shrinkage estimate of a quantitative trait locus (QTL) effect is the posterior mean of the QTL effect when a normal prior distribution is assigned to the QTL. This note gives the derivation of the shrinkage estimate under the multivariate linear model. An important lemma regarding the posterior mean of a normal likelihood combined with a normal prior is introduced. The lemma is then used to derive the Bayesian shrinkage estimates of the QTL effects. PMID- 17720903 TI - Association of polymorphisms in odorant-binding protein genes with variation in olfactory response to benzaldehyde in Drosophila. AB - Adaptive evolution of animals depends on behaviors that are essential for their survival and reproduction. The olfactory system of Drosophila melanogaster has emerged as one of the best characterized olfactory systems, which in addition to a family of odorant receptors, contains an approximately equal number of odorant binding proteins (OBPs), encoded by a multigene family of 51 genes. Despite their abundant expression, little is known about their role in chemosensation, largely due to the lack of available mutations in these genes. We capitalized on naturally occurring mutations (polymorphisms) to gain insights into their functions. We analyzed the sequences of 13 Obp genes in two chromosomal clusters in a population of wild-derived inbred lines, and asked whether polymorphisms in these genes are associated with variation in olfactory responsiveness. Four polymorphisms in 3 Obp genes exceeded the statistical permutation threshold for association with responsiveness to benzaldehyde, suggesting redundancy and/or combinatorial recognition by these OBPs of this odorant. Model predictions of alternative pre-mRNA secondary structures associated with polymorphic sites suggest that alterations in Obp mRNA structure could contribute to phenotypic variation in olfactory behavior. PMID- 17720912 TI - Adaptive evolution of recently duplicated accessory gland protein genes in desert Drosophila. AB - The relationship between animal mating system variation and patterns of protein polymorphism and divergence is poorly understood. Drosophila provides an excellent system for addressing this issue, as there is abundant interspecific mating system variation. For example, compared to D. melanogaster subgroup species, repleta group species have higher remating rates, delayed sexual maturity, and several other interesting differences. We previously showed that accessory gland protein genes (Acp's) of Drosophila mojavensis and D. arizonae evolve more rapidly than Acp's in the D. melanogaster subgroup and that adaptive Acp protein evolution is likely more common in D. mojavensis/D. arizonae than in D. melanogaster/D. simulans. These findings are consistent with the idea that greater postcopulatory selection results in more adaptive evolution of seminal fluid proteins in the repleta group flies. Here we report another interesting evolutionary difference between the repleta group and the D. melanogaster subgroup Acp's. Acp gene duplications are present in D. melanogaster, but their high sequence divergence indicates that the fixation rate of duplicated Acp's has been low in this lineage. Here we report that D. mojavensis and D. arizonae genomes contain several very young duplicated Acp's and that these Acp's have experienced very rapid, adaptive protein divergence. We propose that rapid remating of female desert Drosophila generates selection for continuous diversification of the male Acp complement to improve male fertilization potential. Thus, mating system variation may be associated with adaptive protein divergence as well as with duplication of Acp's in Drosophila. PMID- 17720914 TI - Contrasting rates of evolution in Pm3 loci from three wheat species and rice. AB - The Pm3 gene from wheat confers resistance against powdery mildew and recent studies have shown that it is a member of a multigene family in the wheat genome. We compared genomic sequences ranging from 178 to 332 kb containing six Pm3-like genes and five gene fragments from orthologous loci in the A genome of wheat at three different ploidy levels. We found that the wheat Pm3 loci display an extremely dynamic evolution where sequence conservation is minimal between species and basically limited to very short sequences containing the genetic markers that define the orthology. The Pm3-like genes and their up- and downstream regions were reshuffled by multiple rearrangements, resulting in a complex mosaic of conserved and unique sequences. Comparison with rice showed that the known wheat Pm3-like genes represent only one branch of a large superfamily with several clusters in rice and suggests the presence of additional similar genes in the wheat genome. Estimates of divergence times and transposable element insertions indicate that the Pm3 locus in wheat has undergone more drastic changes in its recent evolution than its counterpart in rice. This indicates that loci containing homologous resistance gene analogs can evolve at highly variable speeds in different species. PMID- 17720916 TI - Stable inheritance of host species-derived microchromosomes in the gynogenetic fish Poecilia formosa. AB - B chromosomes are additional, usually unstable constituents of the genome of many organisms. Their origin, however, is often unclear and their evolutionary relevance is not well understood. They may range from being deleterious to neutral or even beneficial. We have followed the genetic fate of B chromosomes in the asexual, all-female fish Poecilia formosa over eight generations. In this species, B chromosomes come in the form of one to three tiny microchromosomes derived from males of the host species that serve as sperm donors for this gynogenetic species. All microchromosomes have centromeric heterochromatin but usually only one has a telomere. Such microchromosomes are stably inherited, while the telomereless are prone to be lost in both the soma and germline. In some cases the stable microchromosome carries a functional gene lending support to the hypothesis that the B chromosomes in P. formosa could increase the genetic diversity of the clonal lineage in this ameiotic organism and to some degree counteract the genomic decay that is supposed to be connected with the lack of recombination. PMID- 17720911 TI - Genomewide clonal analysis of lethal mutations in the Drosophila melanogaster eye: comparison of the X chromosome and autosomes. AB - Using a large consortium of undergraduate students in an organized program at the University of California, Los Angeles (UCLA), we have undertaken a functional genomic screen in the Drosophila eye. In addition to the educational value of discovery-based learning, this article presents the first comprehensive genomewide analysis of essential genes involved in eye development. The data reveal the surprising result that the X chromosome has almost twice the frequency of essential genes involved in eye development as that found on the autosomes. PMID- 17720915 TI - Gravity force transduced by the MEC-4/MEC-10 DEG/ENaC channel modulates DAF 16/FoxO activity in Caenorhabditis elegans. AB - The gravity response is an array of behavioral and physiological plasticity elicited by changes in ambient mechanical force and is an evolutionarily ancient adaptive mechanism. We show in Caenorhabditis elegans that the force of hypergravity is translated into biological signaling via a genetic pathway involving three factors: the degenerin/epithelial Na(+) channel (DEG/ENaC) class of mechanosensory channels of touch receptor neurons, the neurotransmitter serotonin, and the FoxO transcription factor DAF-16 known to regulate development, energy metabolism, stress responses, and aging. After worms were exposed to hypergravity for 3 hr, their muscular and neuronal functions were preserved, but they exhibited DAF-16::GFP nuclear accumulation in cells throughout the body and accumulated excess fat. Mutations in MEC-4/MEC-10 DEG/ENaC or its partners MEC-6, MEC-7, and MEC-9 blocked DAF-16::GFP nuclear accumulation induced by hypergravity but did not affect DAF-16 response to other stresses. We show that exogenous serotonin and the antidepressant fluoxetine can attenuate DAF-16::GFP nuclear accumulation in WT animals exposed to hypergravity. These results reveal a novel physiological role of the mechanosensory channel, showing that the perception of mechanical stress controls FoxO signaling pathways and that inactivation of DEG/ENaC may decouple mechanical loading and physiological responses. PMID- 17720917 TI - A genomewide study of reproductive barriers between allopatric populations of a homosporous fern, Ceratopteris richardii. AB - Biological factors involved in reproductive barriers between two divergent races of Ceratopteris richardii were investigated. We used a combination of spore germination rates, QTL analysis of spore germination rates, and transmission ratio distortion (TRD) of 729 RFLPs, AFLPs, and isozyme markers distributed across the genome on the basis of hybrid populations of 488 doubled haploid lines (DHLs) and 168 F(2)'s. Substantial reproductive barriers were found between the parental races, predominantly in the form of spore inviability (23.7% F(1) spore viability). Intrinsic genetic factors such as Bateson-Dobzhansky-Muller (BDM) incompatibilities involving both nuclear-nuclear and nuclear-cytoplasmic factors and chromosomal rearrangements appear to contribute to intrinsic postzygotic isolation. The genomewide distribution patterns of TRD loci support the hypothesis that reproductive barriers are a byproduct of divergence in allopatry and that the strong reproductive barriers are attributable to a small number of genetic elements scattered throughout the genome. PMID- 17720920 TI - Mitochondrial DNA phylogeny of cultivated and wild beets: relationships among cytoplasmic male-sterility-inducing and nonsterilizing cytoplasms. AB - Cytoplasmic male sterility (CMS), the maternally inherited failure to produce functional pollen, has been used in the breeding of sugar beet (Beta vulgaris ssp. vulgaris). At least three different sources of CMS can be distinguished from one another as well as from normal fertile cytoplasm by polymorphisms in their mitochondrial genomes. Here we analyzed 50 accessions of cultivated and wild beets to investigate the phylogenetic relationships among male-sterility-inducing and normal cytoplasms. The haplotypes were characterized by the nucleotide sequence of the mitochondrial cox2-cox1 spacer region and mitochondrial minisatellite loci. The results indicated that (1) a normal cytoplasm line, cv. TK81-O, was situated at the major core node of the haplotype network, and (2) the three sterilizing cytoplasms in question derived independently from the core haplotype. The evolutionary pathway was investigated by physical mapping study of the mitochondrial genome of a wild beet (B. vulgaris ssp. orientalis) accession BGRC56777 which shared the same mitochondrial haplotype with TK81-O, but was not identical to TK81-O for the RFLP profiles of mitochondrial DNA. Interestingly, three sets of inverted repeated sequences appeared to have been involved in a series of recombination events during the course of evolution between the BGRC56777 and the TK81-O mitochondrial genomes. PMID- 17720918 TI - Genetic suppressors of Caenorhabditis elegans pha-4/FoxA identify the predicted AAA helicase ruvb-1/RuvB. AB - FoxA transcription factors are critical regulators of gut development and function. FoxA proteins specify gut fate during early embryogenesis, drive gut differentiation and morphogenesis at later stages, and affect gut function to mediate nutritional responses. The level of FoxA is critical for these roles, yet we know relatively little about regulators for this family of proteins. To address this issue, we conducted a genetic screen for mutants that suppress a partial loss of pha-4, the sole FoxA factor of Caenorhabditis elegans. We identified 55 mutants using either chemical or insertional mutagenesis. Forty-two of these were informational suppressors that affected nonsense-mediated decay, while the remaining 13 were pha-4 suppressors. These 13 alleles defined at least six different loci. On the basis of mutational frequencies for C. elegans and the genetic dominance of four of the suppressors, we predict that many of the suppressors are either unusual loss-of-function mutations in negative regulators or rare gain-of-function mutations in positive regulators. We characterized one dominant suppressor molecularly and discovered the mutation alters a likely cis regulatory region within pha-4 itself. A second suppressor defined a new locus, the predicted AAA+ helicase ruvb-1. These results indicate that our screen successfully found cis- or trans-acting regulators of pha-4. PMID- 17720919 TI - Rhythm defects caused by newly engineered null mutations in Drosophila's cryptochrome gene. AB - Much of the knowledge about cryptochrome function in Drosophila stems from analyzing the cryb mutant. Several features of this variant's light responsiveness imply either that CRYb retains circadian-photoreceptive capacities or that additional CRY-independent light-input routes subserve these processes. Potentially to resolve these issues, we generated cry knock-out mutants (cry0's) by gene replacement. They behaved in an anomalously rhythmic manner in constant light (LL). However, cry0 flies frequently exhibited two separate circadian components in LL, not observed in most previous cryb analyses. Temperature dependent circadian phenotypes exhibited by cry(0) flies suggest that CRY is involved in core pacemaking. Further locomotor experiments combined cry0 with an externally blinding mutation (norpAP24), which caused the most severe decrements of circadian photoreception observed so far. cryb cultures were shown previously to exhibit either aperiodic or rhythmic eclosion in separate studies. We found cry0 to eclose in a solidly periodic manner in light:dark cycles or constant darkness. Furthermore, both cry0 and cryb eclosed rhythmically in LL. These findings indicate that the novel cry0 type causes more profound defects than does the cryb mutation, implying that CRYb retains residual activity. Because some norpAP24 cry0 individuals can resynchronize to novel photic regimes, an as-yet undetermined light-input route exists in Drosophila. PMID- 17720921 TI - The Escherichia coli histone-like protein HU has a role in stationary phase adaptive mutation. AB - Stationary phase adaptive mutation in Escherichia coli is thought to be a mechanism by which mutation rates are increased during stressful conditions, increasing the possibility that fitness-enhancing mutations arise. Here we present data showing that the histone-like protein, HU, has a role in the molecular pathway by which adaptive Lac(+) mutants arise in E. coli strain FC40. Adaptive Lac(+) mutations are largely but not entirely due to error-prone DNA polymerase IV (Pol IV). Mutations in either of the HU subunits, HUalpha or HUbeta, decrease adaptive mutation to Lac(+) by both Pol IV-dependent and Pol IV independent pathways. Additionally, HU mutations inhibit growth-dependent mutations without a reduction in the level of Pol IV. These effects of HU mutations on adaptive mutation and on growth-dependent mutations reveal novel functions for HU in mutagenesis. PMID- 17720922 TI - Evolution of mammalian chitinase(-like) members of family 18 glycosyl hydrolases. AB - Family 18 of glycosyl hydrolases encompasses chitinases and so-called chi-lectins lacking enzymatic activity due to amino acid substitutions in their active site. Both types of proteins widely occur in mammals although these organisms lack endogenous chitin. Their physiological function(s) as well as evolutionary relationships are still largely enigmatic. An overview of all family members is presented and their relationships are described. Molecular phylogenetic analyses suggest that both active chitinases (chitotriosidase and AMCase) result from an early gene duplication event. Further duplication events, followed by mutations leading to loss of chitinase activity, allowed evolution of the chi-lectins. The homologous genes encoding chitinase(-like) proteins are clustered in two distinct loci that display a high degree of synteny among mammals. Despite the shared chromosomal location and high homology, individual genes have evolved independently. Orthologs are more closely related than paralogues, and calculated substitution rate ratios indicate that protein-coding sequences underwent purifying selection. Substantial gene specialization has occurred in time, allowing for tissue-specific expression of pH optimized chitinases and chi lectins. Finally, several family 18 chitinase-like proteins are present only in certain lineages of mammals, exemplifying recent evolutionary events in the chitinase protein family. PMID- 17720923 TI - Evolution can favor antagonistic epistasis. AB - The accumulation of deleterious mutations plays a major role in evolution, and key to this are the interactions between their fitness effects, known as epistasis. Whether mutations tend to interact synergistically (with multiple mutations being more deleterious than would be expected from their individual fitness effects) or antagonistically is important for a variety of evolutionary questions, particularly the evolution of sex. Unfortunately, the experimental evidence on the prevalence and strength of epistasis is mixed and inconclusive. Here we study theoretically whether synergistic or antagonistic epistasis is likely to be favored by evolution and by how much. We find that in the presence of recombination, evolution favors less synergistic or more antagonistic epistasis whenever mutations that change the epistasis in this direction are possible. This is because evolution favors increased buffering against the effects of deleterious mutations. This suggests that we should not expect synergistic epistasis to be widespread in nature and hence that the mutational deterministic hypothesis for the advantage of sex may not apply widely. PMID- 17720924 TI - Genetic and haplotypic structure in 14 European and African cattle breeds. AB - To evaluate and compare the extent of LD in cattle, 1536 SNPs, mostly localized on BTA03, were detected in silico from available sequence data using two different methods and genotyped on samples from 14 distinct breeds originating from Europe and Africa. Only 696 SNPs could be validated, confirming the importance of trace-quality information for the in silico detection. Most of the validated SNPs were informative in several breeds and were used for a detailed description of their genetic structure and relationships. Results obtained were in agreement with previous studies performed on microsatellite markers and using larger samples. In addition, the majority of the validated SNPs could be mapped precisely, reaching an average density of one marker every 311 kb. This allowed us to analyze the extent of LD in the different breeds. Decrease of LD with physical distance across breeds revealed footprints of ancestral LD at short distances (<10 kb). As suggested by the haplotype block structure, these ancestral blocks are organized, within a breed, into larger blocks of a few hundred kilobases. In practice, such a structure similar to that already reported in dogs makes it possible to develop a chip of <300,000 SNPs, which should be efficient for mapping purposes in most cattle breeds. PMID- 17720925 TI - State II dissociation element formation following activator excision in maize. AB - Active Activator (Ac) elements undergo mutations to become nonautonomous Dissociation (Ds) elements at a low frequency. To understand the mechanism of Ds formation, we have developed high-throughput genetic and molecular screens to identify these rare Ds derivatives generated from any Ac insertion in the maize genome. Using these methods we have identified 15 new Ds elements derived from Ac insertions at eight different loci. Approximately half of the Ds elements contain filler DNA inserted at the deletion junction that is derived from sequences within or adjacent to Ac. In contrast to previous reports, several of these Ds elements lack direct repeats flanking the deletion junctions and filler DNA in the donor Ac. To accommodate our findings and those of others, we propose a model of slip mispairing during error-prone repair synthesis to explain the formation of state II Ds elements in maize. We discuss the use of these lines and molecular techniques developed here to capture somatic Ds transposition events in two component Ac/Ds tagging programs in maize. PMID- 17720926 TI - The roles of mutation accumulation and selection in loss of sporulation in experimental populations of Bacillus subtilis. AB - Phenotypic loss is an important evolutionary force in nature but the mechanism(s) responsible for loss remains unclear. We used both simulation and multiple regression approaches to analyze data on the loss of sporulation, a complex bacterial developmental process, during experimental evolution of Bacillus subtilis. Neutral processes of mutational degradation alone were sufficient to explain loss-of-sporulation ability in four of five populations, while evidence that selection facilitated mutational loss was found for only one population. These results are discussed in the context of the evolution of sporulation in particular and phenotypic loss in general. PMID- 17720927 TI - Unbiased estimator for genetic drift and effective population size. AB - Amounts of genetic drift and the effective size of populations can be estimated from observed temporal shifts in sample allele frequencies. Bias in this so called temporal method has been noted in cases of small sample sizes and when allele frequencies are highly skewed. We characterize bias in commonly applied estimators under different sampling plans and propose an alternative estimator for genetic drift and effective size that weights alleles differently. Numerical evaluations of exact probability distributions and computer simulations verify that this new estimator yields unbiased estimates also when based on a modest number of alleles and loci. At the cost of a larger standard deviation, it thus eliminates the bias associated with earlier estimators. The new estimator should be particularly useful for microsatellite loci and panels of SNPs, representing a large number of alleles, many of which will occur at low frequencies. PMID- 17720928 TI - A Genetic linkage map of Atlantic halibut (Hippoglossus hippoglossus L.). AB - A genetic linkage map has been constructed for Atlantic halibut on the basis of 258 microsatellites and 346 AFLPs. Twenty-four linkage groups were identified, consistent with the 24 chromosomes seen in chromosome spreads. The total map distance is 1562.2 cM in the female and 1459.6 cM in the male with an average resolution of 4.3 and 3.5 cM, respectively. Using diploid gynogens, we estimated centromere locations in 19 of 24 linkage groups. Overall recombination in the female was approximately twice that of the male; however, this trend was not consistent along the linkage groups. In the centromeric regions, females had 11 17.5 times the recombination of the males, whereas this trend reversed toward the distal end with males having three times the recombination of the females. Correspondingly, in the male, markers clustered toward the centromeric region with 50% of markers within 20 cM of the putative centromere, whereas 35% of markers in the female were found between 60 and 80 cM from the putative centromere. Limited interspecies comparisons within Japanese flounder and Tetraodon nigroviridis revealed blocks of conservation in sequence and marker order, although regions of chromosomal rearrangement were also apparent. PMID- 17720929 TI - The expression pattern of a rice disease resistance gene xa3/xa26 is differentially regulated by the genetic backgrounds and developmental stages that influence its function. AB - Genetic background and developmental stage influence the function of some disease resistance (R) genes. The molecular mechanisms of these modifications remain elusive. Our results show that the two factors are associated with the expression of the R gene in rice Xa3 (also known as Xa26)-mediated resistance to Xanthomonas oryzae pv. oryzae (Xoo), which in turn influences the expression of defense responsive genes. The background of japonica rice, one of the two major subspecies of Asian cultivated rice, facilitates the function of Xa3 more than the background of indica rice, another rice subspecies. Xa3 expression gradually increases from early seedling stage to adult stage. Japonica plants carrying Xa3 regulated by the native promoter showed an enlarged resistance spectrum (i.e., resistance to more Xoo races), an increased resistance level (i.e., further reduced lesion length), and whole-growth-stage resistance compared to the indica rice; this enhanced resistance was associated with an increased expression of Xa3 throughout the growth stages in the japonica plants, which resulted in enhanced expression of defense-responsive genes. Overexpressing Xa3 with a constitutive strong promoter further enhanced rice resistance due to further increased Xa3 transcripts in both indica and japonica backgrounds, whereas regulating Xa3 with a pathogen-induced weak promoter impaired rice resistance. PMID- 17720930 TI - The neutral coalescent process for recent gene duplications and copy-number variants. AB - I describe a method for simulating samples from gene families of size two under a neutral coalescent process, for the case where the duplicate gene either has fixed recently in the population or is still segregating. When a duplicate locus has recently fixed by genetic drift, diversity in the new gene is expected to be reduced, and an excess of rare alleles is expected, relative to the predictions of the standard coalescent model. The expected patterns of polymorphism in segregating duplicates ("copy-number variants") depend both on the frequency of the duplicate in the sample and on the rate of crossing over between the two loci. When the crossover rate between the ancestral gene and the copy-number variant is low, the expected pattern of variability in the ancestral gene will be similar to the predictions of models of either balancing or positive selection, if the frequency of the duplicate in the sample is intermediate or high, respectively. Simulations are used to investigate the effect of crossing over between loci, and gene conversion between the duplicate loci, on levels of variability and the site-frequency spectrum. PMID- 17720931 TI - Identification of mutations that decrease the stability of a fragment of Saccharomyces cerevisiae chromosome III lacking efficient replicators. AB - Eukaryotic chromosomes are duplicated during S phase and transmitted to progeny during mitosis with high fidelity. Chromosome duplication is controlled at the level of replication initiation, which occurs at cis-acting replicator sequences that are spaced at intervals of approximately 40 kb along the chromosomes of the budding yeast Saccharomyces cerevisiae. Surprisingly, we found that derivatives of yeast chromosome III that lack known replicators were replicated and segregated properly in at least 96% of cell divisions. To gain insight into the mechanisms that maintain these "originless" chromosome fragments, we screened for mutants defective in the maintenance of an "originless" chromosome fragment, but proficient in the maintenance of the same fragment that carries its normal complement of replicators (originless fragment maintenance mutants, or ofm). We show that three of these Ofm mutations appear to disrupt different processes involved in chromosome transmission. The OFM1-1 mutant seems to disrupt an alternative initiation mechanism, and the ofm6 mutant appears to be defective in replication fork progression. ofm14 is an allele of RAD9, which is required for the activation of the DNA damage checkpoint, suggesting that this checkpoint plays a key role in the maintenance of the "originless" fragment. PMID- 17720932 TI - Effects of recombination on hitchhiking diversity in the Brassica self incompatibility locus complex. AB - In self-incompatibility, a number of S haplotypes are maintained by frequency dependent selection, which results in trans-specific S haplotypes. The region of several kilobases (approximately 40-60 kb) from SP6 to SP2, including self incompatibility-related genes and some adjacent genes in Brassica rapa, has high nucleotide diversity due to the hitchhiking effect, and therefore we call this region the "S-locus complex." Recombination in the S-locus complex is considered to be suppressed. We sequenced regions of >50 kb of the S-locus complex of three S haplotypes in B. rapa and found higher nucleotide diversity in intergenic regions than in coding regions. Two highly similar regions of >10 kb were found between BrS-8 and BrS-46. Phylogenetic analysis using trans-specific S haplotypes (called interspecific pairs) of B. rapa and B. oleracea suggested that recombination reduced the nucleotide diversity in these two regions and that the genes not involved in self-incompatibility in the S-locus complex and the kinase domain, but not the S domain, of SRK have also experienced recombination. Recombination may reduce hitchhiking diversity in the S-locus complex, whereas the region from the S domain to SP11 would disfavor recombination. PMID- 17720933 TI - Mutational interference and the progression of Muller's ratchet when mutations have a broad range of deleterious effects. AB - Deleterious mutations can accumulate in asexual haploid genomes through the process known as Muller's ratchet. This process has been described in the literature mostly for the case where all mutations are assumed to have the same effect on fitness. In the more realistic situation, deleterious mutations will affect fitness with a wide range of effects, from almost neutral to lethal. To elucidate the behavior of the ratchet in this more realistic case, simulations were carried out in a number of models, one where all mutations have the same effect on selection [one-dimensional (1D) model], one where the deleterious mutations can be divided into two groups with different selective effects [two dimensional (2D) model], and finally one where the deleterious effects are distributed. The behavior of these models suggests that deleterious mutations can be classified into three different categories, such that the behavior of each can be described in a straightforward way. This makes it possible to predict the ratchet rate for an arbitrary distribution of fitness effects using the results for the well-studied 1D model with a single selection coefficient. The description was tested and shown to work well in simulations where selection coefficients are derived from an exponential distribution. PMID- 17720934 TI - Genomewide identification of genes under directional selection: gene transcription Q(ST) scan in diverging Atlantic salmon subpopulations. AB - Evolutionary genomics has benefited from methods that allow identifying evolutionarily important genomic regions on a genomewide scale, including genome scans and QTL mapping. Recently, genomewide scanning by means of microarrays has permitted assessing gene transcription differences among species or populations. However, the identification of differentially transcribed genes does not in itself suffice to measure the role of selection in driving evolutionary changes in gene transcription. Here, we propose and apply a "transcriptome scan" approach to investigating the role of selection in shaping differential profiles of gene transcription among populations. We compared the genomewide transcription levels between two Atlantic salmon subpopulations that have been diverging for only six generations. Following assessment of normality and unimodality on a gene-per-gene basis, the additive genetic basis of gene transcription was estimated using the animal model. Gene transcription h(2) estimates were significant for 1044 (16%) of all detected cDNA clones. In an approach analogous to that of genome scans, we used the distribution of the Q(ST) values estimated from intra- and intersubpopulation additive genetic components of the transcription profiles to identify 16 outlier genes (average Q(ST) estimate = 0.11) whose transcription levels are likely to have evolved under the influence of directional selection within six generations only. Overall, this study contributes both empirically and methodologically to the quantitative genetic exploration of gene transcription data. PMID- 17720935 TI - Molecular population genetics of the male and female mitochondrial DNA molecules of the California sea mussel, Mytilus californianus. AB - The presence of two gender-associated mitochondrial genomes in marine mussels provides a unique opportunity to investigate the dynamics of mtDNA evolution without complications inherent in interspecific comparisons. Here, we assess the relative importance of selection, mutation, and differential constraint in shaping the patterns of polymorphism within and divergence between the male (M) and female (F) mitochondrial genomes of the California sea mussel, Mytilus californianus. Partial sequences were obtained from homologous regions of four genes (nad2, cox1, atp6, and nad5) totaling 2307 bp in length. The M and F mtDNA molecules of M. californianus exhibited extensive levels of nucleotide polymorphism and were more highly diverged than observed in other mytilids (overall Tamura-Nei distances >40%). Consistent with previous studies, the M molecule had significantly higher levels of silent and replacement polymorphism relative to F. Both genomes possessed large numbers of singleton and low frequency mutations that gave rise to significantly negative Tajima's D values. Mutation-rate scalars estimated for silent and replacement mutations were elevated in the M genome but were not sufficient to account for its higher level of polymorphism. McDonald-Kreitman tests were highly significant at all loci due to excess numbers of fixed replacement mutations between molecules. Strong purifying selection was evident in both genomes in keeping the majority of replacement mutations at low population frequencies but appeared to be slightly relaxed in M. Our results suggest that a reduction in selective constraint acting on the M genome remains the best explanation for its greater levels of polymorphism and faster rate of evolution. PMID- 17720936 TI - Functional characterization of pathogenic human MSH2 missense mutations in Saccharomyces cerevisiae. AB - Hereditary nonpolyposis colorectal cancer (HNPCC) is associated with defects in DNA mismatch repair. Mutations in either hMSH2 or hMLH1 underlie the majority of HNPCC cases. Approximately 25% of annotated hMSH2 disease alleles are missense mutations, resulting in a single change out of 934 amino acids. We engineered 54 missense mutations in the cognate positions in yeast MSH2 and tested for function. Of the human alleles, 55% conferred strong defects, 8% displayed intermediate defects, and 38% showed no defects in mismatch repair assays. Fifty percent of the defective alleles resulted in decreased steady-state levels of the variant Msh2 protein, and 49% of the Msh2 variants lost crucial protein-protein interactions. Finally, nine positions are predicted to influence the mismatch recognition complex ATPase activity. In summary, the missense mutations leading to loss of mismatch repair defined important structure-function relationships and the molecular analysis revealed the nature of the deficiency for Msh2 variants expressed in the tumors. Of medical relevance are 15 human alleles annotated as pathogenic in public databases that conferred no obvious defects in mismatch repair assays. This analysis underscores the importance of functional characterization of missense alleles to ensure that they are the causative factor for disease. PMID- 17720937 TI - Modulation of Caenorhabditis elegans transcription factor activity by HIM-8 and the related Zinc-Finger ZIM proteins. AB - The previously reported negative regulatory activity of HIM-8 on the Sox protein EGL-13 is shared by the HIM-8-related ZIM proteins. Furthermore, mutation of HIM 8 can modulate the effects of substitution mutations in the DNA-binding domains of at least four other transcription factors, suggesting broad regulatory activity by HIM-8. PMID- 17720938 TI - Patterns of sequence variability and divergence at the diminutive gene region of Drosophila melanogaster: complex patterns suggest an ancestral selective sweep. AB - To identify putatively swept regions of the Drosophila melanogaster genome, we performed a microsatellite screen spanning a 260-kb region of the X chromosome in populations from Zimbabwe, Ecuador, the United States, and China. Among the regions identified by this screen as showing a complex pattern of reduced heterozygosity and a skewed frequency spectrum was the gene diminutive (dm). To investigate the microsatellite findings, nucleotide sequence polymorphism data were generated in populations from both China and Zimbabwe spanning a 25-kb region and encompassing dm. Analysis of the sequence data reveals strongly reduced nucleotide variation across the entire gene region in both the non African and the African populations, an extended haplotype pattern, and structured linkage disequilibrium, as well as a rejection of neutrality in favor of selection using a composite likelihood-ratio test. Additionally, unusual patterns of synonymous site evolution were observed at the second exon of this locus. On the basis of simulation studies as well as recently proposed methods for distinguishing between selection and nonequilibrium demography, we find that this "footprint" is best explained by a selective sweep in the ancestral population, the signal of which has been somewhat blurred via founder effects in the non-African samples. PMID- 17720940 TI - Disability and psychosocial outcomes in old age. AB - OBJECTIVE: This article explores psychosocial variables associated with illness and age-related losses during old age. METHOD: The study is cross-sectional and comprised 999 people aged 65 and older. The variables included health problems and limitations, self-perceptions of health, optimism, and quality of life. RESULTS: In general, people aged 80+ years show high prevalence of health problems and disability, good self-perception of health, and quality of life. However, among the oldest age group, those in better health were more optimistic, but more problems meant lower self-perception of health, quality of life, and optimism. DISCUSSION: This does not fully confirm the disability paradox (high disability and high optimism and self-perception of quality of life). The dual process coping model helps to understand the results of our study: First is an attempt to avoid losses; afterward, people lower goals and standards to meet constraints and foster adaptation. PMID- 17720939 TI - A ONECUT homeodomain protein communicates X chromosome dose to specify Caenorhabditis elegans sexual fate by repressing a sex switch gene. AB - Sex is determined in Caenorhabditis elegans through a dose-dependent signal that communicates the number of X chromosomes relative to the ploidy, the number of sets of autosomes. The sex switch gene xol-1 is the direct molecular target of this X:A signal and integrates both X and autosomal components to determine sexual fate. X chromosome number is relayed by X signal elements (XSEs) that act cumulatively to repress xol-1 in XX animals, thereby inducing hermaphrodite fate. Ploidy is relayed by autosomal signal elements (ASEs), which counteract the single dose of XSEs in XO animals to activate xol-1 and induce the male fate. Our goal was to identify and characterize new XSEs and further analyze known XSEs to understand the principles by which a small difference in the concentration of an intracellular signal is amplified to induce dramatically different developmental fates. We identified a new XSE, the ONECUT homeodomain protein CEH-39, and showed that it acts as a dose-dependent repressor of xol-1 transcript levels. Unexpectedly, most other XSEs also repress xol-1 predominantly, but not exclusively, at the transcript level. The twofold difference in X dose between XO and XX animals is translated into the male vs. hermaphrodite fate by the synergistic action of multiple, independent XSEs that render xol-1 active or inactive, primarily through transcriptional regulation. PMID- 17720941 TI - Cohort differences in adult obesity in the United States: 1982-2002. AB - OBJECTIVE: To examine the relative importance of broad social change, cohort specific change, and population composition on trends in adult obesity over the past two decades. METHODS: Using the National Health Interview Study from 1982 through 2002, 5-year birth cohorts are examined for differential trends in obesity. Logistic regression is used to separate out the effects of population composition from broad social change and cohort-specific change. RESULTS: Results confirm that age-specific obesity rates have been increasing for successively born cohorts, indicating broad social change. There is little evidence for cohort specific change, and only small effects of compositional change. DISCUSSION: Although increasing diversity in the older population will probably result in higher rates of obesity in the future, increasingly sedentary lives and the uncertain impact of smoking cessation on weight outweigh population composition effects. More research is needed on the impact of lifestyle behaviors on the American population. PMID- 17720944 TI - Bone morphogenetic proteins and their receptors in the eye. AB - The human genome encodes at least 42 different members of the transforming growth factor-beta superfamily of growth factors. Bone morphogenetic proteins (BMPs) are the largest subfamily of proteins within the transforming growth factor-beta superfamily and are involved in numerous cellular functions including development, morphogenesis, cell proliferation, apoptosis, and extracellular matrix synthesis. This article first reviews BMPs and BMP receptors, BMP signaling pathways, and mechanisms controlling BMP signaling. Second, we review BMP and BMP receptor expression during embryonic ocular development/ differentiation and in adult ocular tissues. Lastly, future research directions with respect to BMP, BMP receptors, and ocular tissues are suggested. PMID- 17720945 TI - Physiology of alpha-fetoprotein as a biomarker for perinatal distress: relevance to adverse pregnancy outcome. AB - The many physiologic roles of human alpha-fetoprotein (HAFP) and its correlation with perinatal distress/pregnancy outcome are rarely addressed together in the biomedical literature, even though HAFP has long been used as a biomarker for fetal birth defects. Although the well being of the fetus can be monitored by the measurement of gestational age-dependent HAFP in biologic fluid levels (serum, amniotic fluid, urine, and vaginal fluids) throughout pregnancy, the majority of clinical reports reflect largely second trimester and (less likely) first trimester testing due to regulatory clinical restrictions. However, reports of third-trimester and pregnancy term measurement of HAFP levels performed in clinical research and/or investigational settings have gradually increased over the years and have expanded our base knowledge of AFP-associated pregnancy disorders during these stages. The different structural forms of HAFP (isoforms, epitopes, molecular variants, etc.) detected in the various biologic fluid compartments have been limited by antibody recognition of specific epitopic sites developed by the kit manufacturers based on antibody specificity, sensitivity, and precision. Concomitantly, the advances in elucidating the various biologic actions of AFP are opening new vistas toward understanding the physiologic roles of AFP during pregnancy. The present review surveys HAFP as a biomarker for fetal distress during the perinatal period in view of its structural and functional properties. An attempt is then made to relate the AFP fluid levels to adverse pregnancy complications and outcomes. Hence, the present review was divided into two major sections: (I) AFP structure and function considerations and (II) the relationship of AFP levels to the distressed fetus during the third trimester and at term. PMID- 17720946 TI - Biogenic amine actions on cholangiocyte function. AB - Biogenic amines, such as serotonin, histamine, dopamine, and the catecholamines epinephrine and norepinephrine, regulate a multitude of cellular responses. A great deal of effort has been invested into understanding the effects of these molecules and their corresponding receptor systems on cholangiocyte secretion, apoptosis, and growth. This review summarizes the results of these efforts and highlights the importance of these regulatory molecules on the physiology and pathophysiology of cholangiocytes. PMID- 17720947 TI - Macrophage iron, hepcidin, and atherosclerotic plaque stability. AB - Hepcidin has emerged as the key hormone in the regulation of iron balance and recycling. Elevated levels increase iron in macrophages and inhibit gastrointestinal iron uptake. The physiology of hepcidin suggests an additional mechanism by which iron depletion could protect against atherosclerotic lesion progression. Without hepcidin, macrophages retain less iron. Very low hepcidin levels occur in iron deficiency anemia and also in homozygous hemochromatosis. There is defective retention of iron in macrophages in hemochromatosis and also evidently no increase in atherosclerosis in this disorder. In normal subjects with intact hepcidin responses, atherosclerotic plaque has been reported to have roughly an order of magnitude higher iron concentration than that in healthy arterial wall. Hepcidin may promote plaque destabilization by preventing iron mobilization from macrophages within atherosclerotic lesions; the absence of this mobilization may result in increased cellular iron loads, lipid peroxidation, and progression to foam cells. Marked downregulation of hepcidin (e.g., by induction of iron deficiency anemia) could accelerate iron loss from intralesional macrophages. It is proposed that the minimally proatherogenic level of hepcidin is near the low levels associated with iron deficiency anemia or homozygous hemochromatosis. Induced iron deficiency anemia intensely mobilizes macrophage iron throughout the body to support erythropoiesis. Macrophage iron in the interior of atherosclerotic plaques is not exempt from this process. Decreases in both intralesional iron and lesion size by systemic iron reduction have been shown in animal studies. It remains to be confirmed in humans that a period of systemic iron depletion can decrease lesion size and increase lesion stability as demonstrated in animal studies. The proposed effects of hepcidin and iron in plaque progression offer an explanation of the paradox of no increase in atherosclerosis in patients with hemochromatosis despite a key role of iron in atherogenesis in normal subjects. PMID- 17720948 TI - Experimental hypothyroidism inhibits delta-aminolevulinate dehydratase activity in neonatal rat blood and liver. AB - The aim of this study was to investigate the potential relationship between hypothyroidism and delta-aminolevulinate dehydratase (delta-ALA-D) activity in rat blood and liver. Experimental hypothyroidism was induced in weanling rats by exposing their mothers to propylthiouracil (PTU) diluted in tap water (0.05% w/ v), ad libitum, during the lactational period (PTU group). Control (euthyroid) group included weanling rats whose mothers received just tap water, ad libitum, during the lactational period. Reverted-hypothyroid group (PTU + 3,3',5-triiodo-L thyronine [T(3)]) included weanling rats whose mothers were exposed to PTU similarly to those in the hypothyroid group, but pups received daily subcutaneous injections of T(3) (20 microg/kg, from Postnatal Days 2-20). After the treatment, serum T(3) levels were drastically decreased (around 70%) in the PTU group, and this phenomenon was almost reverted by exogenous T(3). PTU decreased blood delta ALA-D activity by 75%, and T(3) treatment prevented such phenomena. Erythrocytes and hemoglobin levels were increased by 10% in PTU-treated animals and higher increments (around 25%) were observed in these parameters when exogenous T(3) was coadministered. Dithiothreitol did not change blood delta-ALA-D activity of PTU exposed animals when present in the reaction medium, suggesting no involvement of the enzyme's essential thiol groups in PTU-induced delta-ALA-D inhibition. PTU did not affect blood delta-ALA-D activity in vitro. These results are the first to show a correlation between hypothyroidism and decreased delta-ALA-D activity and point to this enzyme as a potential molecule involved with hypothyroidism related hematological changes. PMID- 17720949 TI - Mammary epithelial cells treated concurrently with TGF-alpha and TGF-beta exhibit enhanced proliferation and death. AB - Transforming growth factor-alpha (TGF-alpha) stimulates while TGF-beta inhibits mammary epithelial cell growth, suggesting that when cells are treated concurrently with the growth factors their combined effects would result in no net growth. However, combined treatments stimulate proliferation and cellular transformation in several cell lines. The objective of this paper was to describe the effect of long-term (6 days) concurrent TGF-alpha and TGF-beta treatment on normal mammary epithelial cell growth pattern, morphology, and gene expression. Growth curve analysis showed that TGF-alpha enhanced while TGF-beta suppressed growth rate until Day 4, when cells entered lag phase. However, cells treated concurrently with both growth factors exhibited a dichotomous pattern of growth marked by growth and death phases (with no intermittent lag phase). These changes in growth patterns were due to a marked induction of cell death from Day 2 (16.5%) to Day 4 (89.5%), resulting in the transition from growth to death phases, even though the combined treated cultures had significantly more (P < 0.05) cells in S phase on Day 4. TGF-beta stimulated epithelial to mesenchyme transdifferentiation (EMT) in the presence of TGF-alpha, as characterized by increased expression of fibronectin and changes in TGF-beta receptor binding. Expression patterns of genes that regulate the cell cycle showed significant interaction between treatment and days, with TGF-beta overriding TGF-alpha stimulated effects on gene expression. Overall, the combined treatments were marked by enhanced rates of cellular proliferation, death, and trans differentiation, behaviors reminiscent of breast tumors, and thus this system may serve as a good model to study breast tumorigenesis. PMID- 17720950 TI - Hematologic and urinary excretion anomalies in patients with chronic fatigue syndrome. AB - Patients with chronic fatigue syndrome (CFS) have a broad and variable spectrum of signs and symptoms with variable onsets. This report outlines the results of a single-blind, cross-sectional research project that extensively investigated a large cohort of 100 CFS patients and 82 non fatigued control subjects with the aim of performing a case-control evaluation of alterations in standard blood parameters and urinary amino and organic acid excretion profiles. Blood biochemistry and full blood counts were unremarkable and fell within normal laboratory ranges. However, the case-control comparison of the blood cell data revealed that CFS patients had a significant decrease in red cell distribution width and increases in mean platelet volume, neutrophil counts, and the neutrophil-lymphocyte ratio. Evaluation of the urine excretion parameters also revealed a number of anomalies. The overnight urine output and rate of amino acid excretion were both reduced in the CFS group (P < 0.01). Significant decreases in the urinary excretion of asparagine (P < 0.0001), phenylalanine (P < 0.003), the branch chain amino acids (P < 0.005), and succinic acid (P < 0.0001), as well as increases in 3-methylhistidine (P < 0.05) and tyrosine (P < 0.05) were observed. It was concluded that the urinary excretion and blood parameters data supported the hypothesis that alterations in physiologic homeostasis exist in CFS patients. PMID- 17720951 TI - Mild calorie restriction does not affect testosterone levels and testicular gene expression in mutant mice. AB - The hypothalamic-pituitary-gonadal (HPG) axis and the somatotropic axis are influenced by nutritional factors. Calorie restriction (CR) extends lifespan but suppresses both the HPG and the somatotropic axes. Since most CR studies use a fairly severe (40%-60%) reduction of calorie intake, we hypothesized that a milder CR (20%) might not be deleterious to reproduction in male mice. To test this hypothesis, we evaluated the effects of 20% CR on testicular testosterone content and on testicular expression of genes that are relevant to testicular function and reproductive competence, including insulin-like growth factor-I, cytochrome P450 aromatase (Cyp19a1), androgen receptor, luteinizing hormone receptor, follicle-stimulating hormone receptor, cytochrome P450c17 and 3-beta hydroxysteroid dehydrogenase/isomerase. To relate CR effects to the activity of the somatotropic axis, we have used growth hormone-resistant GHR knockout mice as well as transgenic mice overexpressing GH. Mild CR did not affect testosterone levels in testis homogenates and had little effect on expression of the examined genes in the reproductive organs. Altered activity of the GH/insulin-like growth factor-1 axis had a major impact on the parameters analyzed. The results also suggest that expression of several key genes involved in the control of testicular function is preserved under conditions of mild CR and encourage speculation that mild regimens of CR can produce longevity benefits without impairing reproduction. PMID- 17720952 TI - Subcutaneous fat accumulation shows a beneficial correlation with serum cholesterol in postmenopausal Japanese women. AB - This study aimed to investigate whether accumulation of subcutaneous abdominal fat has a beneficial correlation with lipid metabolism in premenopausal and/or postmenopausal Japanese women. The study enrolled 146 premenopausal women, ranging in age from 19 to 54 years, and 82 postmeno-pausal women, ranging in age from 47 to 66 years. Fat distribution, including abdominal visceral fat area (VFA) and abdominal subcutaneous fat area (SFA), were measured in an outpatient clinic by magnetic resonance imaging. Homogeneity of the regression slopes for SFA to total cholesterol (P = 0.030), low-density lipoprotein cholesterol (P = 0.020), apolipoprotein B (apoB) (P = 0.001), and the ratio of apoB to apolipoprotein A-I (apoA-I) (P = 0.003) were not found between premenopausal and postmenopausal women, even after adjustment for both VFA and age. However, the regression slopes for VFA to all measured lipid parameters, as well as apolipoproteins, were homogeneous between the premenopausal and postmeno-pausal groups. Abdominal SFA in postmenopausal women correlated negatively with total cholesterol (P = 0.007), low-density lipoprotein cholesterol (P = 0.002), apoB (P < 0.001), and the ratio of apoB to apoA-I (P = 0.001), after adjustment for age and VFA, but this was not the case in premenopausal women. The mechanisms involved in the beneficial effects of subcutaneous fat accumulation in postmenopausal women remain obscure, but upregulated aromatase expression, derived from adipose tissue, may possibly improve lipid and apolipoprotein metabolism. PMID- 17720953 TI - Flaxseed alone or in combination with tamoxifen inhibits MCF-7 breast tumor growth in ovariectomized athymic mice with high circulating levels of estrogen. AB - Flaxseed (FS) is rich in mammalian lignan precursors and alpha-linolenic acid, which have been suggested as having anticancer effects. Previous studies have shown that 10% FS inhibits the growth of human estrogen-dependent breast cancer (MCF-7) in athymic mice, and it enhances the inhibitory effect of tamoxifen (TAM). This study determined whether the effect of FS, alone or in combination with TAM, is dose dependent, and it explored the potential mechanism of action. Ovariectomized athymic mice with estradiol (E2) supplementation (1.7 mg/pellet, 60-day release) and established MCF-7 tumors were treated with basal diet control (0FS), 5% FS (5FS), 10% FS (10FS), and TAM (TAM/ 0FS; 5 mg/pellet, 60-day release), alone or in combination (TAM/ 5FS and TAM/10FS) for 8 weeks. Compared with control, 5FS and 10FS significantly inhibited tumor growth by 26% and 38%, respectively. TAM/0FS had an effect similar to the 10FS. TAM/ 5FS and TAM/10FS, respectively, induced significant 48% and 43% reductions in tumor size compared with 0FS, and 18% and 10% reductions compared with TAM/0FS. The relative uterine weight was significantly lower in all TAM groups compared with the control. The reduction of tumor growth resulted from decreased cell proliferation and increased cell apoptosis. TAM/ 5FS caused a significantly higher expression of estrogen receptor-alpha (ERalpha) compared with 5FS and TAM/0FS, whereas TAM/10FS had a higher ERalpha than 10FS and TAM/0FS. Compared with the control, progesterone receptor (PgR) expression was significantly reduced in all treatment groups, but insulin-like growth factor-1 (IGF-1) expression was reduced only by 10FS, TAM/5FS and TAM/10FS. Tumor cell proliferation was significantly positively associated with expression of PgR and IGF-1 and negatively associated with apoptosis and ERalpha. Apoptosis was only associated with ERalpha. In conclusion, FS inhibited MCF-7 tumor growth in a dose-dependent manner and enhanced the inhibitory effect of TAM due to the modulation of ER and growth factor signal transduction pathways. PMID- 17720954 TI - In Vivo evaluation of a PAMAM-cystamine-(Gd-DO3A) conjugate as a biodegradable macromolecular MRI contrast agent. AB - Macromolecular Gd(III) chelates are superior magnetic resonance imaging (MRI) contrast agents for blood pool and tumor imaging. However, their clinical development is limited by the safety concerns related to the slow excretion and long-term gadolinium tissue accumulation. A generation 6 PAMAM Gd(III) chelate conjugate with a cleavable disulfide spacer, PAMAM-G6-cystamine-(Gd-DO3A), was prepared as a biodegradable macromolecular MRI contrast agent with rapid excretion from the body. T(1) and T(2) relaxivities of the contrast agent were 11.6 and 13.3 mM(-1)sec(-1) at 3T, respectively. Blood pool and tumor contrast enhancement of the agent were evaluated in female nude mice bearing MDA-MB-231 human breast carcinoma xenografts with a nondegradable conjugate PAMAM-G6-(Gd DO3A) as a control. PAMAM-G6-cystamine-(Gd-DO3A) resulted in significant contrast enhancement in the blood for about 5 mins, and Gd-DO3A was released from the conjugate and rapidly excreted via renal filtration after the disulfide spacer was cleaved. The nondegradable control had much longer blood circulation and excreted more slowly from the body. PAMAM-G6-cystamine-(Gd-DO3A) also resulted in more prominent tumor contrast enhancement than the control. However, PAMAM-G6 cystamine-(Gd-DO3A) demonstrated high toxicity due to the intrinsic toxicity of PAMAM dendrimers. In conclusion, although PAMAM-G6-cystamine-(Gd-DO3A) showed some advantages compared with the nondegradable control, PAMAM dendrimers are not suitable carriers for biodegradable macromolecular MRI contrast agents, due to their high toxicity. PMID- 17720956 TI - Evaluation of poly (glycerol-adipate) nanoparticle uptake in an in vitro 3-D brain tumor co-culture model. AB - Despite the inherent problems associated with in vivo animal models of tumor growth and metastases, many of the current in vitro brain tumor models also do not accurately mimic tumor-host brain interactions. Therefore, there is a need to develop such co-culture models to study tumor biology and, importantly, the efficacy of drug delivery systems targeting the brain. So far, few investigations of this nature have been published. In this paper we describe the development of a new model system and its application to drug delivery assessment. For our new model, a co-culture of DAOY cell brain tumor aggregates and organo-typic brain slices was developed. Initially, the DAOY aggregates attached to cerebellum slices and invaded as a unit. Single cells in the periphery of the aggregate detached from the DAOY aggregates and gradually replaced normal brain cells. This invasive behavior of DAOY cells toward organotypic cerebellum slices shows a similar pattern to that seen in vivo. After validation of the co-culture model using transmission electron microscopy, nanoparticle (NP) uptake was then evaluated. Confocal micrographs illustrated that DAOY cells in this co-culture model took up most of the NPs, but few NPs were distributed into brain cells. This finding corresponded with results of NP uptake in DAOY and brain aggregates reported elsewhere. PMID- 17720955 TI - Doxorubicin and beta-lapachone release and interaction with micellar core materials: experiment and modeling. AB - Polymer micelles with two different core-forming blocks, poly(d,l -lactide) (PLA) and poly(epsilon-caprolactone) (PCL), but the same coronal material, poly(ethylene glycol) (PEG), were investigated in this study as nanoscopic drug carriers. The release of two different drugs, doxorubicin (DOX) and beta lapachone (beta-lap), from PEG(5k)-b-PCL(5k) and PEG(5k)-b-PLA(5k) micelles was studied at pH 5.0 and 7.4. Mathematical solutions of both Higuchi's model and Fickian diffusion equations were utilized to elucidate the differences between the micelle core materials for the two drugs. The neutral and smaller of the two drugs tested, beta-lap, demonstrated faster, pH-independent release, suggesting that no substantial changes occurred in either micelle core at lower pH. In contrast, the release rate of DOX was found to noticeably increase at lower pH with a larger cumulative amount of drug released. Different core materials were shown to have considerable influence on the release kinetics of both drugs: in both cases, the more hydrophobic PCL core showed slower drug release rates compared with the less hydrophobic PLA core. PMID- 17720957 TI - Gene expression analysis of murine lungs following pulmonary exposure to Asian sand dust particles. AB - The respiratory health impact of Asian sand dust events originating in the deserts of China has become a concern within China and in its neighboring countries. We examined the effects of Asian sand dust particles (ASDPs) on gene expression in the murine lung using microarray analysis and elucidated the components responsible for lung inflammation. Male ICR mice were intratracheally administrated ASDPs, heat-treated ASDPs (ASDP-F, lipopolysaccaride [LPS], or beta glucan free), or kaolin particles. We performed microarray analysis for murine lungs, the results of which were confirmed by quantitative reverse transcription polymerase chain reaction (RT-PCR). We also assessed the protein expression and histologic changes. Exposure to ASDP, ASDP-F, or kaolin upregulated (>2-fold) 112, 36, or 9 genes, respectively, compared with vehicle exposure. In particular, ASDP exposure markedly enhanced inflammatory response-related genes, including chemokine (C-X-C motif) ligand 1/keratinocyte-derived chemokine, chemokine (C-X-C motif) ligand 2/macrophage inflammatory protein-2, chemokine (C-C motif) ligand 3/macrophage inflammatory protein-1alpha, and chemokine (C-X-C motif) ligand 10/interferon-gamma-inducible protein-10 (>6-fold). The results were correlated with those of the quantitative RT-PCR and the protein expression analyses in overall trend. In contrast, exposure to ASDP-F attenuated the enhanced expression of these proinflammatory molecules. Kaolin exposure increased the expression of genes and proteins for the chemokines. In histopathologic changes, exposure to ASDP prominently enhanced pulmonary neutrophilic inflammation, followed by kaolin and ASDP-F exposure in the order. Taken together, exposure to ASDP causes pulmonary inflammation via the expression of proinflammatory molecules, which can be attributed to LPS and beta-glucan absorbed in ASDPs. Furthermore, microarray analysis should be effective for identifying potentially novel genes, sensitive biomarkers, and pathways involved in the health effects of the exposure to environmental particles (e.g., ASDPs). PMID- 17720960 TI - Theaflavins attenuate hepatic lipid accumulation through activating AMPK in human HepG2 cells. AB - Black tea is one of the world's most popular beverages, and its health-promoting effects have been intensively investigated. The antiobesity and hypolipidemic effects of black tea have attracted increasing interest, but the mechanisms underlying these phenomena remain unclear. In the present study, the black tea major component theaflavins were assessed for their hepatic lipid-lowering potential when administered in fatty acid overload conditions both in cell culture and in an animal experimental model. We found that theaflavins significantly reduced lipid accumulation, suppressed fatty acid synthesis, and stimulated fatty acid oxidation. Furthermore, theaflavins also inhibited acetyl coenzyme A carboxylase activities by stimulating AMP-activated protein kinase (AMPK) through the LKB1 and reactive oxygen species pathways. These observations support the idea that AMPK is a critical component of decreased hepatic lipid accumulation by theaflavin treatments. Our results show that theaflavins are bioavailable both in vitro and in vivo and may be active in the prevention of fatty liver and obesity. PMID- 17720959 TI - Differential regulation of bile acid homeostasis by the farnesoid X receptor in liver and intestine. AB - Bile acid concentrations are controlled by a feedback regulatory pathway whereby activation of the farnesoid X receptor (FXR) represses transcription of both the CYP7A1 gene, encoding the rate-limiting enzyme in the classic bile acid synthesis pathway, and the CYP8B1 gene, required for synthesis of cholic acid. The tissue specific roles of FXR were examined using liver- and intestine-specific FXR-null models. FXR deficiency in either liver (Fxr DeltaL) or intestine (Fxr DeltaIE) increased bile acid pool size. Treatment with the FXR-selective agonist GW4064 significantly repressed CYP7A1 in Fxr DeltaL mice but not Fxr DeltaIE mice, demonstrating that activation of FXR in intestine but not liver is required for short-term repression of CYP7A1 in liver. This intestinal-specific effect of FXR is likely mediated through induction of the hormone FGF15, which suppresses CYP7A1. In comparison to CYP7A1, FXR-mediated repression of CYP8B1 was more dependent on the presence of FXR in liver and less dependent on its presence in intestine. Consistent with these findings, recombinant FGF15 repressed CYP7A1 mRNA levels without affecting CYP8B1 expression. These data provide evidence that FXR-mediated repression of bile acid synthesis requires the complementary actions of FXR in both liver and intestine and reveal mechanistic differences in feedback repression of CYP7A1 and CYP8B1. PMID- 17720961 TI - Clinical signs and pathology shown by British sheep and cattle infected with bluetongue virus serotype 8 derived from the 2006 outbreak in northern Europe. AB - Four poll Dorset sheep and four Holstein-Friesian cattle were infected with the northern European strain of bluetongue virus (BTV), BTV-8, to assess its pathogenicity in UK breeds. The time course of infection was monitored in both species by using real-time reverse transcriptase-PCR (RT-PCR), conventional RT PCR and serology. Two of the sheep developed severe clinical signs that would have been fatal in the field; the other two were moderately and mildly ill, respectively. The cattle were clinically unaffected, but had high levels of viral RNA in their bloodstream. Real-time RT-PCR detected viral RNA as early as one day after infection in the cattle and three days after infection in the sheep. Antibodies against BTV were detected by six days after infection in the sheep and eight days after infection in the cattle. Postmortem examinations revealed pathology in the cattle that was more severe than suggested by the mild clinical signs, but the pathological and clinical findings in the sheep were more consistent. PMID- 17720962 TI - Glial fibrillary acidic protein (GFAP) and anti-GFAP autoantibody in canine necrotising meningoencephalitis. AB - To establish clinical markers for canine necrotising meningoencephalitis (NME) and to elucidate its pathogenesis, glial fibrillary acidic protein (GFAP) and anti-GFAP autoantibodies were measured in the cerebrospinal fluid (CSF) of 32 dogs with NME, 23 dogs with other inflammatory central nervous system (CNS) diseases, 27 dogs with miscellaneous CNS diseases and 25 healthy dogs, including five pugs. The dogs with NME had the highest levels of anti-GFAP autoantibodies. The diagnostic sensitivity and specificity of anti-GFAP autoantibodies for NME were 91 per cent and 73 per cent, respectively. Some of the dogs with NME and the healthy pugs, had high CSF concentrations of GFAP, suggesting a breed-specific fragility of astrocytes. The leakage of GFAP and the development of autoimmunity may be key to understanding the pathogenesis of NME. PMID- 17720963 TI - Plasma concentrations of voriconazole in falcons. AB - Doses of 12.5 mg voriconazole/kg bodyweight administered every 12 hours by crop gavage to six falcons for 14 days provided peak plasma concentrations of more than 1 microg/ml, but the trough concentrations were lower and sometimes undetectable. Administering the same doses incorporated into meat that was fed to one falcon for seven days and to three falcons for up to 91 days provided similar plasma concentrations. PMID- 17720965 TI - Surgical treatment of a parotid duct sialolith in a bulldog. PMID- 17720964 TI - Optimisation of the response to respiratory virus vaccines in cattle. PMID- 17720966 TI - Diagnostic evaluation of real-time PCR in the detection of Rhodococcus equi in faeces and nasopharyngeal swabs from foals with pneumonia. PMID- 17720967 TI - Control of Salmonella Gallinarum in Swiss fancy breed flocks. PMID- 17720969 TI - Delivering animal health and welfare. PMID- 17720968 TI - Polymelia associated with frequent chromosome breaks in a heifer. PMID- 17720970 TI - Outbreak of avian influenza virus H5N1 in India. PMID- 17720971 TI - Toxoplasma in cetaceans around the British Isles. PMID- 17720972 TI - House crows and the spread of pathogens. PMID- 17720973 TI - Parasite control strategies. PMID- 17720974 TI - Nitro-fatty acid reaction with glutathione and cysteine. Kinetic analysis of thiol alkylation by a Michael addition reaction. AB - Fatty acid nitration by nitric oxide-derived species yields electrophilic products that adduct protein thiols, inducing changes in protein function and distribution. Nitro-fatty acid adducts of protein and reduced glutathione (GSH) are detected in healthy human blood. Kinetic and mass spectrometric analyses reveal that nitroalkene derivatives of oleic acid (OA-NO2) and linoleic acid (LNO2) rapidly react with GSH and Cys via Michael addition reaction. Rates of OA NO2 and LNO2 reaction with GSH, determined via stopped flow spectrophotometry, displayed second-order rate constants of 183 M(-1)S(-1) and 355 M(-1)S(-1), respectively, at pH 7.4 and 37 degrees C. These reaction rates are significantly greater than those for GSH reaction with hydrogen peroxide and non-nitrated electrophilic fatty acids including 8-iso-prostaglandin A2 and 15-deoxy Delta(12,14)-prostaglandin J2. Increasing reaction pH from 7.4 to 8.9 enhanced apparent second-order rate constants for the thiol reaction with OA-NO2 and LNO2, showing dependence on the thiolate anion of GSH for reactivity. Rates of nitroalkene reaction with thiols decreased as the pKa of target thiols increased. Increasing concentrations of the detergent octyl-beta-d-glucopyranoside decreased rates of nitroalkene reaction with GSH, indicating that the organization of nitro fatty acids into micellar or membrane structures can limit Michael reactivity with more polar nucleophilic targets. In aggregate, these results reveal that the reversible adduction of thiols by nitro-fatty acids is a mechanism for reversible post-translational regulation of protein function by nitro-fatty acids. PMID- 17720975 TI - Mapping the binding site on small ankyrin 1 for obscurin. AB - Small ankyrin 1 (sAnk1), an integral protein of the sarcoplasmic reticulum encoded by the ANK1 gene, binds with nanomolar affinity to the C terminus of obscurin, a giant protein surrounding the contractile apparatus in striated muscle. We used site-directed mutagenesis to characterize the binding site on sAnk1, specifically addressing the role of two putative amphipathic, positively charged helices. We measured binding qualitatively by blot overlay assays and quantitatively by surface plasmon resonance and showed that both positively charged sequences are required for activity. We showed further that substitution of a lysine or arginine with an alanine or glutamate located at the same position along either of the two putative helices has similar inhibitory or stimulatory effects on binding and that the effects of a particular mutation depended on the position of the mutated amino acid in each helix. We modeled the structure of the binding region of sAnk1 by homology with ankyrin repeats of human Notch1, which have a similar pattern of charged and hydrophobic residues. Our modeling suggested that each of the two positively charged sequences forms pairs of amphipathic, anti-parallel alpha-helices flanked by beta-hairpin-like turns. Most of the residues in homologous positions along each helical unit have similar, though not identical, orientations. CD spectroscopy confirmed the alpha-helical content of sAnk1, approximately 33%, predicted by the model. Thus, structural and mutational studies of the binding region on sAnk1 for obscurin suggest that it consists of two ankyrin repeats with very similar structures. PMID- 17720977 TI - Exploring ecological significance of tree crown plasticity through three dimensional modelling. AB - BACKGROUND AND AIMS: Morphogenetic plasticity may be as important as physiological plasticity in determining plant adaptability to changing environmental conditions. This study examines the importance of crown plasticity of trees in stands. METHODS: A three-dimensional forest simulator is used to explore the impact of crown shape plasticity on tree growth. Crown deformation is mediated through the local response to light and overall allometric constraints governing tree dimensions. By altering shape response parameters of Hevea brasiliensis the impact of increased or decreased plasticity is explored in a variety of competitive environments defined by various combinations of tree density and relative frequency of different strategies. The possible interactions between plasticity and growth rate and plasticity and below-ground competition are also explored. KEY RESULTS: Crown plasticity confers competitive superiority in all cases studied. Interactions with other processes may downplay or enhance this competitive advantage. CONCLUSIONS: Simulation results strongly suggest that crown plasticity does have a significant impact on tree performance in nature and that commonly observed crown shape deformation response of trees is of adaptive value. PMID- 17720976 TI - Growth factor induction of Cripto-1 shedding by glycosylphosphatidylinositol phospholipase D and enhancement of endothelial cell migration. AB - Cripto-1 (CR-1) is a glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein that has been shown to play an important role in embryogenesis and cellular transformation. CR-1 is reported to function as a membrane-bound co receptor and as a soluble ligand. Although a number of studies implicate the role of CR-1 as a soluble ligand in tumor progression, it is unclear how transition from the membrane-bound to the soluble form is physiologically regulated and whether differences in biological activity exist between these forms. Here, we demonstrate that CR-1 protein is secreted from tumor cells into the conditioned medium after treatment with serum, epidermal growth factor, or lysophosphatidic acid, and this soluble form of CR-1 exhibits the ability to promote endothelial cell migration as a paracrine chemoattractant. On the other hand, membrane-bound CR-1 can stimulate endothelial cell sprouting through direct cell-cell interaction. Shedding of CR-1 occurs at the GPI-anchorage site by the activity of GPI-phospholipase D (GPI-PLD), because CR-1 shedding was suppressed by siRNA knockdown of GPI-PLD and enhanced by overexpression of GPI-PLD. These findings describe a novel molecular mechanism of CR-1 shedding, which may contribute to endothelial cell migration and possibly tumor angiogenesis. PMID- 17720978 TI - Seedling growth strategies in Bauhinia species: comparing lianas and trees. AB - BACKGROUND AND AIMS: Lianas are expected to differ from trees in their growth strategies. As a result these two groups of woody species will have different spatial distributions: lianas are more common in high light environments. This study determines the differences in growth patterns, biomass allocation and leaf traits in five closely related liana and tree species of the genus Bauhinia. METHODS: Seedlings of two light-demanding lianas (Bauhinia tenuiflora and B. claviflora), one shade-tolerant liana (B. aurea), and two light-demanding trees (B. purpurea and B. monandra) were grown in a shadehouse at 25% of full sunlight. A range of physiological, morphological and biomass parameters at the leaf and whole plant level were compared among these five species. KEY RESULTS: The two light-demanding liana species had higher relative growth rate (RGR), allocated more biomass to leaf production [higher leaf mass fraction (LMF) and higher leaf area ratio (LAR)] and stem mass fraction (SMF), and less biomass to the roots [root mass fraction (RMF)] than the two tree species. The shade-tolerant liana had the lowest RGR of all five species, and had a higher RMF, lower SMF and similar LMF than the two light-demanding liana species. The two light-demanding lianas had lower photosynthetic rates per unit area (A(area)) and similar photosynthetic rates per unit mass (A(mass)) than the trees. Across species, RGR was positively related to SLA, but not to LAR and A(area). CONCLUSIONS: It is concluded that the faster growth of light-demanding lianas compared with light demanding trees is based on morphological parameters (SLA, LMF and LAR), and cannot be attributed to higher photosynthetic rates at the leaf level. The shade tolerant liana exhibited a slow-growth strategy, compared with the light demanding species. PMID- 17720979 TI - Orthostatic hypotension: a new classification system. AB - AIMS: Orthostatic hypotension (OH) is a common condition, which is defined as a reduction in systolic blood pressure of >or=20 mmHg or diastolic blood pressure of >or=10 mmHg within 3 min of orthostatic stress. Utilizing total peripheral resistance (TPR) and cardiac output (CO) measurements during tilt-table testing (Modelflow method), we classified OH into three categories, namely arteriolar, venular, and mixed. The principle defect in arteriolar OH is impaired vasoconstriction after orthostatic stress, reflected by absence of the compensatory increase in TPR. In venular OH, the predominant defect is excessive reduction in venous return, reflected by a large drop in CO after orthostatic stress with marked tachycardia. Mixed OH is due to a combination of both these mechanisms. METHODS AND RESULTS: We analysed haemodynamic parameters of 110 patients with OH and categorized them as arteriolar, venular, or mixed. Significant differences between the groups were found for the magnitude and time to reach nadir of the systolic blood pressure drop post-head-up tilt. The mixed OH category had the largest systolic blood pressure reduction (42.5, 31.9, 53.3 mmHg, P < 0.001) and the longest nadir time (18.6, 20, 30.7 s, P = 0.002). CONCLUSION: This is a practical classification tool and when validated physiologically, this system could be useful in directing treatment of OH. PMID- 17720980 TI - A functional polymorphism of the Galphaq (GNAQ) gene is associated with accelerated mortality in African-American heart failure. AB - Galphaq, encoded by the human GNAQ gene, is an effector subunit of the Gq heterotrimeric G-protein and the convergence point for signaling of multiple Gq coupled neurohormonal receptors. To identify naturally occurring mutations that could modify GNAQ transcription, we examined genomic DNA isolated from 355 normal subjects for genetic variants in transcription factor binding motifs. Of seven variants identified, the most common was a GC to TT dinucleotide substitution at 694/-695 (allele frequency of 0.467 in Caucasians and 0.329 in African Americans) within a GC-rich domain containing consensus binding sites for Sp-1, c-rel and EGR-1. In promoter-reporter analyses, the TT substitution increased promoter activity in cultured neonatal rat cardiac myocytes and human HEK fibroblasts by approximately 30% at baseline and after stimulation with phorbol ester. Two other relatively common polymorphisms, -173G/A and -168G/A, did not affect promoter activity. Since altered expression/activity of Galphaq is implicated in heart disease, we re-sequenced the GNAQ promoter in 1052 prospectively followed heart failure patients. The TT variant was not increased in heart failure, but was associated with decreased survival time among African Americans, with an adjusted RR of death/cardiac transplant of 1.95 (95% CI = 1.21-3.13) for heterozygotes and 2.4 (95% CI = 1.36-4.26) for homozygotes. Gel mobility shift assays showed that this GC/TT substitution eliminated Sp-1 binding without affecting c-rel or EGR-1 binding to this promoter fragment. Thus, the GNAQ -694/-695 promoter polymorphism alters transcription factor binding, increases promoter activity and adversely affects outcome in human heart failure. PMID- 17720981 TI - An improved algorithm for clustering gene expression data. AB - MOTIVATION: Recent advancements in microarray technology allows simultaneous monitoring of the expression levels of a large number of genes over different time points. Clustering is an important tool for analyzing such microarray data, typical properties of which are its inherent uncertainty, noise and imprecision. In this article, a two-stage clustering algorithm, which employs a recently proposed variable string length genetic scheme and a multiobjective genetic clustering algorithm, is proposed. It is based on the novel concept of points having significant membership to multiple classes. An iterated version of the well-known Fuzzy C-Means is also utilized for clustering. RESULTS: The significant superiority of the proposed two-stage clustering algorithm as compared to the average linkage method, Self Organizing Map (SOM) and a recently developed weighted Chinese restaurant-based clustering method (CRC), widely used methods for clustering gene expression data, is established on a variety of artificial and publicly available real life data sets. The biological relevance of the clustering solutions are also analyzed. PMID- 17720982 TI - A comparison of background correction methods for two-colour microarrays. AB - MOTIVATION: Microarray data must be background corrected to remove the effects of non-specific binding or spatial heterogeneity across the array, but this practice typically causes other problems such as negative corrected intensities and high variability of low intensity log-ratios. Different estimators of background, and various model-based processing methods, are compared in this study in search of the best option for differential expression analyses of small microarray experiments. RESULTS: Using data where some independent truth in gene expression is known, eight different background correction alternatives are compared, in terms of precision and bias of the resulting gene expression measures, and in terms of their ability to detect differentially expressed genes as judged by two popular algorithms, SAM and limma eBayes. A new background processing method (normexp) is introduced which is based on a convolution model. The model-based correction methods are shown to be markedly superior to the usual practice of subtracting local background estimates. Methods which stabilize the variances of the log-ratios along the intensity range perform the best. The normexp+offset method is found to give the lowest false discovery rate overall, followed by morph and vsn. Like vsn, normexp is applicable to most types of two-colour microarray data. AVAILABILITY: The background correction methods compared in this article are available in the R package limma (Smyth, 2005) from http://www.bioconductor.org. SUPPLEMENTARY INFORMATION: Supplementary data are available from http://bioinf.wehi.edu.au/resources/webReferences.html. PMID- 17720983 TI - MeTaDoR: a comprehensive resource for membrane targeting domains and their host proteins. AB - MOTIVATION: Protein-lipid interactions play a central role in cellular signaling and membrane trafficking and at the core of these interactions are domains specialized in lipid binding and membrane targeting. Considering the importance of these domains, we have created MeTaDoR, a comprehensive resource dedicated to membrane targeting domains (MTDs). RESULT: MeTaDoR begins with a brief introduction about all the important MTDs including their subcellular localization and structural features. Sequences of all known MTDs are then provided in two formats: standard Prosite format and a parsed tab-delimited format that provides a manually curated classification into binding or non binding. Structures of all MTDs and host proteins known so far are provided with links to PDB and Pfam databases. Membrane-binding orientation of these proteins, whether experimentally determined or proposed, is also provided with links to the appropriate literature. To facilitate molecular dynamics studies of these proteins, the force-field parameters for many non-standard lipids that commonly interact with these proteins are also provided. Finally, an online server for predicting membrane-binding proteins and a search function with various search fields are included. The resource is publicly available and will be updated on a regular basis. PMID- 17720984 TI - Tools for visually exploring biological networks. AB - Many tools exist for visually exploring biological networks including well-known examples such as Cytoscape, VisANT, Pathway Studio and Patika. These systems play a key role in the development of integrative biology, systems biology and integrative bioinformatics. The trend in the development of these tools is to go beyond 'static' representations of cellular state, towards a more dynamic model of cellular processes through the incorporation of gene expression data, subcellular localization information and time-dependent behavior. We provide a comprehensive review of the relative advantages and disadvantages of existing systems with two goals in mind: to aid researchers in efficiently identifying the appropriate existing tools for data visualization; to describe the necessary and realistic goals for the next generation of visualization tools. In view of the first goal, we provide in the Supplementary Material a systematic comparison of more than 35 existing tools in terms of over 25 different features. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 17720985 TI - Metal reduction kinetics in Shewanella. AB - MOTIVATION: Metal reduction kinetics have been studied in cultures of dissimilatory metal reducing bacteria which include the Shewanella oneidensis strain MR-1. Estimation of system parameters from time-series data faces obstructions in the implementation depending on the choice of the mathematical model that captures the observed dynamics. The modeling of metal reduction is often based on Michaelis-Menten equations. These models are often developed using initial in vitro reaction rates and seldom match with in vivo reduction profiles. RESULTS: For metal reduction studies, we propose a model that is based on the power law representation that is effectively applied to the kinetics of metal reduction. The method yields reasonable parameter estimates and is illustrated with the analysis of time-series data that describes the dynamics of metal reduction in S.oneidensis strain MR-1. In addition, mixed metal studies involving the reduction of Uranyl (U(VI)) to the relatively insoluble tetravalent form (U(IV)) by S. alga strain (BR-Y) were studied in the presence of environmentally relevant iron hydrous oxides. For mixed metals, parameter estimation and curve fitting are accomplished with a generalized least squares formulation that handles systems of ordinary differential equations and is implemented in Matlab. It consists of an optimization algorithm (Levenberg-Marquardt, LSQCURVEFIT) and a numerical ODE solver. Simulation with the estimated parameters indicates that the model captures the experimental data quite well. The model uses the estimated parameters to predict the reduction rates of metals and mixed metals at varying concentrations. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 17720986 TI - Ardalan-Shoja-Kiuru syndrome--hereditary gelsolin amyloidosis plus retinitis pigmentosa. PMID- 17720987 TI - The role of renal biopsy in women with kidney disease identified in pregnancy. AB - BACKGROUND: Renal disease may present for the first time in pregnancy, either as symptomatic disease or as a consequence of antenatal screening. The role of antenatal and post-partum percutaneous renal biopsy in the management of such patients is discussed. METHODS: We describe two series of women; the first is a series of 20 women presenting with renal disease of a severity to warrant renal biopsy during pregnancy whilst the second, comprises 75 women who had an initial presentation of renal disease in pregnancy and underwent post-partum renal biopsy. RESULTS: Biopsy during pregnancy revealed a glomerular disorder in 19/20 (95%) with immediate change of management in 9/20 (40%). In 17/20 (85%) there was delivery of a live infant at median gestation of 36 weeks (range 25-40). Follow up of women [median 103.3 months (2.5-256)] showed 9/20 (45%) had a GFR of <60 ml/min/1.73 m(2) [six at end-stage renal failure (ESRF)] and 3/20 were dead. The majority (62/75; 82.6%) of women undergoing post-partum renal biopsy presented with significant proteinuria (40% pre-eclampsia) during pregnancy not resolving post-partum. A glomerular abnormality was found in 64%. At last follow-up of 47 women [median 51.5 months (range 1-212)], 14 patients (29.7%) had significant proteinuria and 20 (42.6%) had a GFR<60 ml/min/1.73 m(2). Six women (12.7%) had ESRF. CONCLUSIONS: Diagnosis and follow-up of renal disease diagnosed in pregnancy is important as progressive disease occurs in this group. Routine antenatal screening provides a useful diagnostic opportunity to detect asymptomatic renal disease. In a selected sub-group, renal biopsy during pregnancy can be helpful in initiation of correct treatment and allowing progression of pregnancy to fetal viability. PMID- 17720988 TI - Incidence and severity of early electrolyte abnormalities following autologous haematopoietic stem cell transplantation. AB - BACKGROUND: Haematopoietic stem cell transplantation (HSCT) has gained worldwide acceptance as a therapeutic option for many haematological and non-haematological conditions. Local experience supports that electrolyte abnormalities are quite common; however, the incidence and timing of these abnormalities are unknown. METHOD: We conducted a retrospective descriptive study of 48 consecutive adult patients in order to study the incidence and the timing of electrolyte abnormalities following autologous HSCT. Clinical and pharmacological data were collected by the review of patient charts. Potassium, magnesium, calcium, phosphorus and albumin levels were retrieved from the laboratory. RESULTS: HSCT was performed for multiple myeloma (28/48), lymphoma (8/48), Hodgkin disease (4/48), amyloidosis (4/48) and other neoplasia (4/48). At baseline, 21% of patients (10/48) had low electrolyte levels. Following autologous HSCT, hypokalaemia occurred in 81% (39/48), hypomagnesaemia in 67% (32/48), hypocalcaemia in 49% (17/35) and hypophosphataemia in 91% (39/43) of the patients. The nadir of the electrolyte levels occurred between day 8 and 10 after stem cell transplant while the engraftment occurred at day 11.6+/-0.6. The use of amphotericin B and furosemide was associated with more pronounced hypokalaemia and hypomagnesaemia. Hypocalcaemia was more pronounced in patients with multiple myeloma. High levels of electrolytes occurred in only 25% of the patients, none of which required specific treatment. CONCLUSION: We conclude that low electrolyte levels are extremely common after HSCT and the pathophysiology of these abnormalities are complex and multifactorial. PMID- 17720989 TI - Incidence of biopsy-proven glomerulonephritis. AB - BACKGROUND: The reported biopsy-proven glomerulonephritis incidence varies according to population characteristics, the unknown true glomerulonephritis incidence and biopsy rate. Reported glomerulonephritis incidence should be evaluated against the biopsy rate. METHODS: We report here the glomerulonephritis incidence in our University Hospital (UH) consecutive biopsy material. It is compared to those from surrounding central hospitals (CH), previous single-centre studies and European biopsy registries (EBR). Biopsy rate, when reported, has been considered. RESULTS: The annual biopsy rate/10(5), median (min-max), at the UHs was 25.4 (15.6-35.1). At the CHs it was 8.7 (5.1-12.6). In previous single centre studies it has been 18.7-21.5. In the EBRs it has been between 1.0 and 6.9 when reported. The annual incidences (median, min-max) per 10(5) (1980-2000) at the UH were as follows: proliferative glomerulonephritis (9.5, 6.8-18.1), non proliferative glomerulonephritis (6.7, 3.4-12.6), the four major glomerulonephritis groups MesGN (7.7, 4.4-15.9), ECGN/FPGN-complex (1.4, 0.5 3.2), MCGP/FSGS-complex (0.9, 0.2-2.7) and MGN (1.4, 0.5-2.4) these which findings were compatible with the single-centre studies and higher than those of the CHs and in the EBRs. Biopsy rate had a major impact on the annual glomerulonephritis incidences explaining 60% of the variation. The relative frequency of MesGN was the highest by all observers, followed by the ECGN/FPGN complex, MGN and MCGP/FSGS-complex whose frequencies did not differ much. For every patient commencing renal replacement therapy (Finnish Renal Replacement Registry Data) due to glomerulonephritis there were about 11 subjects with biopsy proven glomerulonephritis, a relationship compatible with previous reports. CONCLUSIONS: The incidence of any glomerulonephritis of 17.6 per 10(5) population was comparable to those from the single-centre studies, but higher than in European biopsy registries, a fact largely explained by biopsy rates. PMID- 17720990 TI - Serum phosphorus and the risk of progression of chronic kidney disease. PMID- 17720991 TI - Intention and outcome in guideline-based nephrological practice: a suitable space for 'clinical technology'. PMID- 17720992 TI - T-wave alternans: predicting the unpredictable? PMID- 17720993 TI - Urocortin 2 infusion in human heart failure. AB - AIMS: To document the haemodynamic, neurohormonal, and renal responses to Urocortin 2 (UCN2) infused in human heart failure (HF). METHODS AND RESULTS: Eight male patients with HF [left ventricular ejection fraction (LVEF) < 40%, NYHA class II-III] received placebo and 25 [low dose (LD)] and 100 microg [high dose (HD)] of UCN2 intravenously over 1 h in a single-blind, placebo-controlled, dose-escalation design. UCN2 increased cardiac output (CO) (mean peak increments +/- SEM; placebo 0.3 +/- 0.1; LD 1.0 +/- 0.3; HD 2.0 +/- 0.2 L/min; P < 0.001) and LVEF (0.0 +/- 1.5; LD 5.9 +/- 2.1; HD 14.1 +/- 2.7%; P = 0.001) and decreased mean arterial pressure (placebo 6.7 +/- 1.3; LD 11.4 +/- 1.7; HD 19.4 +/- 3.3 mmHg; P = 0.001), systemic vascular resistance (SVR) (placebo 104 +/- 37; LD 281 +/- 64; HD 476 +/- 79 dynes s/cm(5); P < 0.003), and cardiac work (CW) (placebo 48 +/- 12; LD 66 +/- 22; HD 94 +/- 13 mmHg/L/min; P < 0.001). No significant effect on vasoconstrictor/volume-retaining neurohormones was noted. UCN2 decreased urinary volume (P = 0.035) but not creatinine excretion (P = 0.962). CONCLUSION: Intravenous UCN2 in HF induced increases in CO and LVEF with falls in SVR and CW. No hormone response occurred. The role of UCN2 in circulatory regulation and its potential therapeutic application in heart disease warrant further investigation. PMID- 17720994 TI - Apolipoprotein E-deficient lipoproteins induce foam cell formation by downregulation of lysosomal hydrolases in macrophages. AB - Apolipoprotein E (apoE) deficiency has been suggested to induce foam cell formation. Using lipoproteins obtained from wild-type mice and apoE-deficient mice expressing apoB-48 but not apoB-100, we studied apoE-deficient lipoprotein induced changes in lipoprotein catabolism and protein expression in mouse peritoneal macrophages (MPMs). Our data demonstrate that incubation of MPMs with apoE-deficient lipoproteins induced intracellular lipoprotein, cholesteryl ester, and triglyceride accumulation, which was associated with a time-related decline in apoE-deficient lipoprotein degradation in MPMs. Confocal microscopy analysis indicated that the accumulated lipids were localized in lysosomes. ApoE-deficient lipoproteins reduced the protein levels of lysosomal acid lipase, cathepsin B, and cation-dependent mannose 6 phosphate receptor (MPR46). Exogenous apoE reduced apoE-deficient lipoprotein-induced lipid accumulation and attenuated the suppressive effect of apoE-deficient lipoproteins on lysosomal hydrolase and MPR46 expression. Although oxidized lipoproteins also increased lipid contents in MPMs, exogenous apoE could not attenuate oxidized lipoprotein-induced lipid accumulation. Our in vivo studies also showed that feeding apoE-deficient mice a high-fat diet resulted in cholesteryl ester and triglyceride accumulation and reduced lysosomal hydrolase expression in MPMs. These data suggest that apoE deficient lipoproteins increase cellular lipid contents through pathways different from those activated by oxidized lipoproteins and that reducing lysosomal hydrolases in macrophages might be a mechanism by which apoE-deficient lipoproteins result in intralysosomal lipoprotein accumulation, thereby inducing foam cell formation. PMID- 17720995 TI - HIV disease progression: immune activation, microbes, and a leaky gut. AB - Recent findings indicate that the majority of all CD4+ T lymphocytes are lost during acute HIV infection, with mucosal compartments being most severely affected. The frequency of infection is very high in gut CD4+ T cells, and depletion of these cells persists into the chronic phase of infection. Infection is associated with increased gut permeability, with microbial translocation being evidenced by increased circulating lipopolysaccharide (LPS) levels. Plasma LPS levels correlate with systemic immune activation, which drives chronic HIV infection. Antiretroviral therapy reduces plasma LPS, and greater CD4+ T cell reconstitution is associated with lower LPS levels. These findings have a number of implications for therapeutic strategies. This article summarizes a presentation on HIV disease progression made by Daniel Douek, MD, PhD, at an International AIDS Society-USA Continuing Medical Education course in San Francisco in May 2007. The original presentation is available as a Webcast at www.iasusa.org. PMID- 17720996 TI - Update of the drug resistance mutations in HIV-1: 2007. PMID- 17720997 TI - Incorporating novel virologic tests into clinical practice. AB - Virologic assays continue to evolve in order to meet the needs of HIV-infected patients and their health care providers. Genotypic and phenotypic assays for resistance to reverse transcriptase inhibitors, protease inhibitors, and fusion inhibitors have clear roles in disease management, with both types of assay having advantages and disadvantages. The failure of current assays to identify or measure the presence of minority resistant variants has clinical implications, since presence of such variants is associated with increased risk of virologic failure. Viral fitness may be relevant to disease management, but clinical role of available assays has not been determined. HIV coreceptor tropism assays will also be a crucial tool in the use of coreceptor antagonists, and data are emerging that will define pathways to treatment failure when using these new agents and the new integrase inhibitors. One clear finding for all antiretroviral drugs is that they select for resistance and must be used with good optimized background therapy to avoid virologic failure. This article summarizes a presentation on viral assays made by Eric S. Daar, MD, at an International AIDS Society-USA Continuing Medical Education course in Chicago in May 2007. The original presentation is available as a Webcast at www.iasusa.org. PMID- 17720998 TI - Human papillomavirus infection in HIV-infected persons. AB - Rates of cervical and anal human papillomavirus (HPV) infection and abnormal cytology are high in HIV-infected women, as are rates of anal HPV infection and abnormal cytology in HIV-infected men who have sex with men (MSM). Available evidence indicates that the incidence of anal cancer in HIV-infected MSM has increased in association with prolonged life expectancy achieved with antiretroviral therapy. Routine screening for cervical neoplasia is recommended for HIV-infected women. Routine screening is not yet universally recommended for anal neoplasia, although it should be considered for at-risk patients, particularly given recent improvements in local treatments. A preventive vaccine against cervical HPV infection is approved for use in young women before onset of sexual activity and acquisition of HPV infection. Its potential benefit in preventing anal infection in women and men has yet to be determined, and its potential utility in those with HIV infection remains unknown. This article summarizes a presentation on HPV infection in HIV-infected patients made by Joel Palefsky, MD, at an International AIDS Society-USA Continuing Medical Education course in Chicago in May 2007. The original presentation is available as a Webcast at www.iasusa.org. PMID- 17720999 TI - Elite control of HIV Infection: implications for vaccines and treatment. AB - Spontaneous and sustained ("elite," or aviremic) control of HIV infection (ie, maintaining HIV RNA to less than 50 copies/mL in the absence of therapy) appears to occur in approximately 1 in 300 HIV-infected persons, and represents a distinct phenotype among HIV-infected individuals. Through a recently established international collaboration called the HIV Controller Consortium, over 300 elite controllers have been identified and blood samples collected. These ongoing studies will not only examine the immune responses to HIV that elite controllers generate, but will also make use of a newly available approach to defining the genetic basis of disease. Specifically, the consortium is attempting to determine the genetic basis underlying spontaneous control by performing whole genome analysis scans together with functional immunology studies in a large population of elite controllers. The goal of these studies is to provide insights that will help define the crucial parameters present in persons who are able to control HIV infection, similar to the control most people have with Epstein-Barr virus and varicella, namely by holding the virus in check. These findings could assist in the development of vaccines and new therapies. This article summarizes a presentation on spontaneous control of HIV infection and its implications for vaccine development made by Bruce D. Walker, MD, at an International AIDS Society USA Continuing Medical Education course in New York in March 2007. The original presentation is available as a Webcast at www.iasusa.org. PMID- 17721000 TI - Preconception health care for HIV-infected women. AB - The advent of potent antiretroviral therapy coupled with the dramatic reduction in mother-to-child transmission seen over the past decade has allowed women with HIV infection to live longer, healthier lives and has affected their fertility desires. As a result, preconception health care for HIV-infected women should be a routine part of primary health care. Such counseling includes health recommendations and counseling for safer sexual practices, contraception, and pregnancy planning, identifies individual risks and corresponding interventions, provides personalized and nonjudgmental education, and provides access to integrated services that address all of a woman's health and psychological needs. The goals are: (1) to improve the health of the woman before conception; (2) to identify risk factors for adverse maternal or fetal outcomes and initiate interventions to optimize outcomes; and (3) to prevent transmission of HIV to infants as well as sexual partners. This article will review the components of preconception health care for HIV-infected women. PMID- 17721002 TI - The mechanism of overcoming multidrug resistance (MDR) of fungi by amphotericin B and its derivatives. AB - Comparative studies were performed to determine the activity and cytotoxicity of amphotericin B (AmB) and its derivatives on standard strain of Saccharomyces cerevisiae and its transformants with cloned genes from Candida albicans encoding multidrug resistance (MDR) pumps of ATP-binding cassette and major facilitator superfamilies. The AmB derivatives: amphotericin B 3-dimethylaminopropyl amide and N-methyl-N-D-fructopyranosylamphotericin B methyl ester were shown to be fungistatic and fungicidal towards MDR strains, by membrane permeabilization mechanism. Antibiotic-cell interaction monitored by energy transfer method indicates similar membrane affinity in parent strain and its MDR transformants. Experiments with fungal cells loaded with rhodamine 6G point to lack of competition between this dye and AmB and its derivatives for efflux driven by CDR2p. It can be thus assumed that AmB and its derivatives overcome fungal MDR by not being substrates of the multidrug exporting pumps, presumably due to their large molecular volumes. PMID- 17721001 TI - Novel azalides derived from sixteen-membered macrolides. AB - The design and synthesis of novel 15-membered 11-azalides and 16-membered 11,12 diazalide starting from 16-membered macrolides are reported. A mobile linear dialdehyde was isolated via a cyclic tetraol which was prepared by osmium oxidation of a conjugated diene. One-pot macrocyclization of this dialdehyde with an amine or a diamine afforded corresponding 15-membered azalides or 11,12 diazalide. Fundamental SAR studies of 15-membered 11-azalides disclosed their potentiality as a lead molecule for further chemical modifications. For environmental preservation, sustainable chemistry for synthesis of these azalides is also discussed. PMID- 17721003 TI - Protoplast fusion and gene recombination in the uncommon Actinomycete Planobispora rosea producing GE2270. AB - An efficient method for protoplast generation for the uncommon actinomycete Planobispora rosea, the producer of the thiazolylpeptide antibiotic GE2270, was developed using a combination of hen egg white lysozyme and Streptomyces globisporus mutanolysin. This method converted more than 70% of vegetative mycelium to protoplasts, which were then regenerated with 50% efficiency in an optimized medium. When P. rosea protoplasts were efficiently fused, recombination between different antibiotic (streptomycin and gentamicin) resistance markers originated sensitive strains (str(s)gen(s)) at frequencies as high as 18% and double resistant fusants (str(r)gen(r)) at frequencies as high as 29%. Double resistant fusants showed GE2270 productivity intermediate between the productivity of the parental strains. Protoplast generation and fusion in P. rosea makes whole genome shuffling feasible as an approach to be used alternately with classical random mutagenesis in industrial strain improvement programs. PMID- 17721004 TI - YCM1008A, a novel Ca2+-signaling inhibitor, produced by Fusarium sp. YCM1008. AB - In the course of screening for drugs that suppress the Ca(2+)-mediated growth inhibition in a yeast mutant, we found that the metabolite of Fusarium sp. strain YCM1008 inhibited Ca(2+)-signaling. A novel pyrano-pyridone, YCM1008A was isolated from the fermentation broth using HLB column chromatography followed by HPLC, and the structure was elucidated by spectral analysis. YCM1008A suppressed Ca(2+)-induced growth inhibition of the Saccharomyces cerevisiae (Deltazds1Deltasyr1) mutant. PMID- 17721005 TI - A novel nuclear export inhibitor JBIR-02, a new piericidin discovered from Streptomyces sp. ML55. AB - A new member of the piericidin family, JBIR-02, was isolated from mycelium of Streptomyces sp. ML55 together with two known piericidin derivatives, piericidin A(1) and IT-143-B. The structure was determined on the basis of spectroscopic data. JBIR-02 inhibited nuclear export of beta-arrestin in HeLa cells at the concentration of 20 microM. PMID- 17721006 TI - Isolation and absolute configuration of SMTP-0, a simplest congener of the SMTP family nonlysine-analog plasminogen modulators. AB - SMTP-0, a new simple congener of the SMTP nonlysine-analog plasminogen modulators, was isolated from a culture of Stachybotrys microspora. Based on the physico-chemical data, SMTP-0 was shown to be an enantiomer of the antimicrobial compound stachybotrin B. The absolute configuration of SMTP-0 was determined by the modified Mosher method. The stereochemistry was further confirmed using an epimer of SMTP-0. Unlike most SMTPs with an amino acid side chain linked to the nitrogen atom of the lactam moiety, SMTP-0, which lacks the N-linked side chain, showed no plasminogen modulator activity. PMID- 17721007 TI - Stabilization effect of resin on the production of potent proteasome inhibitor NPI-0052 during submerged fermentation of Salinispora tropica. AB - Addition of acrylic resin Amberlite XAD-7 during the fermentation of Salinispora tropica significantly enhanced the production of NPI-0052 by 69 fold. Examination of the time course of resin addition to the Salinispora tropica fermentation demonstrated that the increase in the production of NPI-052 is due to the stabilization effect by resin but not the removal of an end product feedback repression. Delay in resin addition to the fermentation led to decreases in the production of NPI-0052 to the amounts that are synthesized prior to the resin addition. PMID- 17721008 TI - Unstable angina and non-ST elevation acute coronary syndrome: epidemiology and current management in Japan (Japan Multicenter Investigation for Cardiovascular Disease-D (JMIC-D) Committee). AB - BACKGROUND: A multicenter study was conducted to assess the current medical management of unstable angina (UA) and non-ST-elevation acute coronary syndrome in Japan. METHODS AND RESULTS: This study presents the results of a nationwide questionnaire survey of 770 sites and a case report investigation performed at 20 sites. The questionnaire survey revealed that the number of acute myocardial infarction (AMI) patients treated annually was 1.56-fold greater than the number of UA patients. Non-ST-elevation AMI accounted for 17% of all patients with AMI. Analysis of case reports for 885 UA patients showed extensive use of invasive treatment. In the UA patients, the cumulative incidence of a composite endpoint (all-cause mortality, AMI, and urgent coronary revascularization) was 2% at 1 month and 9% at 6 months. Stratified analysis with respect to the composite endpoint through 6 months showed a significantly lower incidence in patients treated with a calcium-channel blocker than in patients not treated with a calcium-channel blocker. CONCLUSIONS: In Japan, fewer patients are hospitalized annually for treatment of UA than for AMI. The largest percentage of UA patients had Braunwald class III disease. Non-ST-elevation AMI is managed in Japan according to the principle of early invasive treatment, resembling the treatment for ST-elevation AMI. The outcome of treatment is better for Japanese UA patients than for Japanese AMI patients. PMID- 17721009 TI - Usefulness of hydrophilic vs lipophilic statins after acute myocardial infarction: subanalysis of MUSASHI-AMI. AB - BACKGROUND: Statins are widely used to reduce blood levels of low-density lipoprotein-cholesterol (LDL-C). Each statin has unique pharmacokinetic properties; lipophilicity is one such property and relates to tissue selectivity. METHODS AND RESULTS: The Multicenter Study for Aggressive Lipid-lowering Strategy by HMG-CoA Reductase Inhibitors in Patients with Acute Myocardial Infarction (MUSASHI-AMI) trial evaluated the effect of discretional statin treatment initiated within 96 h after onset of acute myocardial infarction (AMI) in Japanese patients. To clarify whether statin lipophilicity affects prognosis, a post hoc analysis of the MUSASHI-AMI database was performed. Patients who were assigned to receive statin were separated into 2 groups according to the lipophilicity of the statins they were administered: lipophilic statins (atorvastatin, fluvastatin, pitavastatin and simvastatin; LS group; n=131) or hydrophilic statins (pravastatin; HS group; n=110). There was no difference in baseline LDL-C concentrations between the 2 groups. Although LDL-C was decreased more potently in the LS than HS groups (-34% vs -19%; p=0.0069), acute coronary syndrome events tended to occur less frequently (3.6% vs 9.9%; p=0.0530) and the incidence of new Q-wave appearance in electrocardiogram was significantly lower (75% vs 89%; p=0.0056) in the HS than LS groups. CONCLUSIONS: In normocholesterolemic Japanese patients after AMI, hydrophilic pravastatin could be superior to lipophilic statins at preventing new Q-wave appearance and reducing cardiovascular events. PMID- 17721010 TI - Serum creatinine on admission predicts long-term mortality in acute myocardial infarction patients undergoing successful primary angioplasty: data from the Heart Institute of Japan Acute Myocardial Infarction (HIJAMI) Registry. AB - BACKGROUND: Data about the long-term mortality of acute myocardial infarction (AMI) patients with renal insufficiency who received sufficient early revascularization are scant, so the present study evaluated the impact of serum creatinine levels on the long-term mortality in patients with AMI undergoing successful primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: The Heart Institute of Japan Acute Myocardial Infarction (HIJAMI) registry has 3,021 consecutive AMI patients. Primary PCI was attempted in 1,451 patients and successful revascularization was obtained in 1,359 patients (93.6%). An elevated serum creatinine level, defined as creatinine > or =1.2 mg/dl, was observed in 216 patients (15.8%). Univariate analyses showed statistical differences between normal and elevated serum creatinine groups in age, gender, hypertension, previous myocardial infarction, number of diseased vessels and Killip class. During a median follow-up period of 39 [32-49] months, the event-free survival rate was lower in elevated creatinine group than normal creatinine group. Multivariate Cox proportional hazards model showed that serum creatinine level was an independent predictor of long-term mortality (adjusted hazard ratio 1.43 [95% confidence interval 1.03-1.99]). CONCLUSION: The serum creatinine level on admission in patients with AMI predicts long-term mortality, even in those with successful primary PCI. PMID- 17721011 TI - Long-term outcome of first-generation metallic coronary stent implantation in patients with coronary artery disease: observational study over a decade. AB - BACKGROUND: In the era of drug-eluting stents, percutaneous coronary intervention (PCI) has been considered an established therapeutic modality for patients with coronary artery disease (CAD). However, little is known about the long-term prognosis. METHODS AND RESULTS: Using data obtained from a single-center registry for cases of first-generation bare metallic stent (BMS) implantation, a 10-year follow-up study in patients with CAD was performed. Data for 125 serial patients (aged 62+/-9 years, 104 males) in whom a BMS was successfully implanted was analyzed. Cardiac death (n=16 [12.8%]), including sudden cardiac death (n=9 [7.2%]), non-cardiac death (n=17 [13.6%]) and non-fatal acute myocardial infarction (n=16 [12.8%]) were documented. At 10 years, cumulative probabilities of target and non-target lesion revascularization were 20.5% and 41.5%, respectively, and only 39.2% of the patients were free from cardiac events (cardiac death/myocardial infarction/unplanned revascularization). Age and left ventricular ejection fraction (LVEF) were significant predictors of total death, and LVEF and the use of diuretics were predictors of cardiac events. CONCLUSIONS: Stabilization of the initial stented site was relatively good and the majority of cardiac events might have originated in non-target lesions. Prevention of systemic arteriosclerosis progression is important for patients with CAD, even after successful PCI. PMID- 17721013 TI - Stroke complicating percutaneous coronary intervention in patients with acute myocardial infarction. AB - BACKGROUND: Stroke associated with percutaneous coronary intervention (PCI) is a tragic complication. Despite advances in the practice of PCI, the incidence of stroke complicating PCI has not changed over the decades. The objective of the present study was to evaluate incidence and correlates of stroke occurring in patients with myocardial infarction (MI) undergoing PCI. METHODS AND RESULTS: Stroke was defined as the presence of any new focal neurological deficit lasting > or =24 h that occurred anytime during or after PCI until discharge. In 2,281 consecutive patients with PCIs for non-ST-elevation MI, or ST-elevation MI (STEMI), 20 strokes were identified (0.88%). Strokes were ischemic in 95%. On multivariate analyses, ejection fraction < or =30% (odds ratio =4.3, p=0.003) was the only independent predictor for stroke. In patients who developed stroke within 24 h of PCI, PCI of vein grafts was more frequent, and use of glycoprotein IIb/IIIa inhibitor was less frequent. Those patients tended to present late in the course of MI. Stroke found more than 24 h after PCI was related to diabetes, higher serum creatinine, lower ejection fraction, anterior wall STEMI and emergency use of intra-aortic balloon pumps. CONCLUSIONS: Low ejection fraction was the only independent predictor for stroke, but risk factors for periprocedural stroke are different from those of stroke occurring more than 24 h after PCI. Upstream use of glycoprotein IIb/IIIa inhibitor might decrease the risk of periprocedural stroke. PMID- 17721012 TI - Renal insufficiency is related to painless myocardial infarction. AB - BACKGROUND: Acute myocardial infarction (MI) sometimes occurs without painful symptoms and in such cases, prognosis is worsened by delays in diagnosis and revascularization. Renal insufficiency induces many types of neuropathy, but the relation between renal insufficiency and painless MI remains unclear. METHODS AND RESULTS: Patients with MI and elevated creatine kinase levels were retrospectively analyzed. Renal insufficiency (serum creatinine concentration > or =1.5 mg/dl) and other characteristics (age, sex, body mass index, hypertension, smoking, diabetes mellitus, dyslipidemia, history of stroke, previous MI, hemodialysis, and atrial fibrillation) were compared between patients who had MI with painful symptoms (painful MI, n=131) and patients who had MI without painful symptoms (painless MI, n=18). Other variables compared were the time from symptom onset to admission, peak creatine kinase concentration, Killip class, site of MI, emergency coronary angiography, postprocedural Thrombolysis In Myocardial Infarction grade III flow, and in hospital death. Univariate analysis identified older age, renal insufficiency, and previous MI as predictors of painless MI. Patients with painless MI showed higher rates of Killip class > or =II and in-hospital death and a longer time from symptom onset to admission. However, multivariate analysis identified only renal insufficiency as an independent predictor of painless MI. CONCLUSIONS: MI without painful symptoms frequently develops in patients who have renal insufficiency, so the possibility of painless MI should be evaluated in such patients to ensure early diagnosis and treatment. PMID- 17721014 TI - Effects of plasma adiponectin levels on the number and function of endothelial progenitor cells in patients with coronary artery disease. AB - BACKGROUND: It is not known whether plasma adiponectin levels are associated with the number and function of endothelial progenitor cells (EPCs) in patients with coronary artery disease (CAD). METHODS AND RESULTS: Plasma levels of adiponectin were measured in 70 patients undergoing coronary angiography. The numbers of colony-forming units (CFUs) of EPCs and senescent EPCs, determined by acidic beta galactosidase staining, were counted. The angiogenic growth factors in the culture medium were also measured. There was a significant positive correlation between adiponectin level and CFUs (r=0.257, p<0.05) but not with the occurrence of senescent EPCs. Next, patients were divided into a high adiponectin group (high ADP: > or =6.17 microg/ml, n=36) and low adiponectin group (low ADP: <6.17 microg/ml, n=34). The number of diseased coronary arteries was less in the high ADP group than that in the low ADP patients (1.7+/-0.8 vs 2.1+/-0.7, p<0.05). No significant differences between the 2 groups were demonstrated in angiogenic growth factors secreted from EPCs. CONCLUSIONS: The results suggest that plasma adiponectin levels are associated with the number of EPCs in patients with CAD. PMID- 17721015 TI - Clinical and angiographic characteristics of acute myocardial infarction caused by vasospastic angina without organic coronary heart disease. AB - BACKGROUND: Vasospastic angina (VA) can occasionally cause acute myocardial infarction (AMI). METHODS AND RESULTS: From January 2003 to June 2005, coronary spastic angina was diagnosed in 292 patients by performing spasm provocation tests. Among the 292 patients, 21 (7.2% of all the VA patients) had an AMI. There were 20 patients who initially visited the emergency room for AMI without suffering prior VA. One patient with a history of VA had an AMI when he discontinued his medication. Among the 21 VA patients with AMI, 14 had experienced severe emotional stress before they visited the emergency room. The spasm provocation test showed that the VA patients with AMI had more multivessel and diffuse spasm than the VA patients without AMI (p<0.001). CONCLUSION: Clinically, the VA patients with AMI usually had their first symptom of VA as the severe chest pain of AMI. Two-thirds of the VA patients with AMI had experienced emotional stress before their AMI. Angiographically, the spasm provocation test for VA patients with AMI showed more multivessel and diffuse spasm than in VA patients without AMI. PMID- 17721016 TI - Early and mid-term impacts of cardiopulmonary bypass on coronary artery bypass grafting in patients with poor left ventricular dysfunction: a propensity score analysis. AB - BACKGROUND: Cardiopulmonary bypass may exacerbate myocardial damage in compromised left ventricles. Early and mid-term outcomes of off-pump coronary artery bypass grafting (OPCAB) vs on-pump coronary artery bypass grafting (On pump CABG) were compared in patients with poor left ventricular dysfunction, using an analysis of a propensity score matching. METHODS AND RESULTS: Between December 2000 and November 2005, 1,473 patients underwent isolated coronary artery bypass grafting in our institute and 153 patients who had a left ventricular ejection fraction (LVEF) lower than 35% were enrolled. The OPCAB group contained 100 patients and the On-pump CABG group contained 53 patients. Preoperative risk factors were compared and 50 patients in each group were matched. The mean follow-up time was 35.5+/-17.3 months. Three deaths (3.0%) occurred in the matched cohort, with no significant difference between 2 groups. The operation time, ventilation time, intensive care unit admission time and occurrence of respiratory failure were significantly lower in the OPCAB group. The mean LVEF of the 2 groups improved significantly. The overall 6-year actuarial survival rates of the OPCAB and On-pump CABG group were 88.2% and 72.4% (p=0.2), respectively, and there were no significant differences in 6-year rates of freedom from major adverse cardiac and cerebrovascular events (p=0.97). CONCLUSIONS: Coronary artery bypass grafting in patients with poor left ventricular dysfunction improved myocardial function. Postoperative respiratory failure was significantly related to the cardiopulmonary bypass for surgical myocardial revascularization. Off-pump and On-pump surgical revascularization resulted in equivalent mid-term outcomes. PMID- 17721017 TI - Preoperative risk stratification with myocardial perfusion imaging in intermediate and low-risk non-cardiac surgery. AB - BACKGROUND: Perioperative cardiac risk in high risk surgery is often stratified with myocardial perfusion single-photon emission computed tomography (SPECT). However, little and no data are available about intermediate and low-risk surgery, respectively. METHODS AND RESULTS: A total of 1,220 consecutive patients underwent electrocardiography-gated dipyridamole stress SPECT to evaluate myocardial perfusion and cardiac function before intermediate or low risk non cardiac surgery. Variables predictive of perioperative cardiac events were determined and the usefulness of combining pretest information and the incremental prognostic value of SPECT was estimated. The frequency of all cardiac events depended on clinical risk factors and type of surgical procedures. After sorting the patients with clinical risk factors and surgical risk, assessment of myocardial perfusion or cardiac function yielded significant risk stratification in intermediate, but not in low-risk surgery. Adding functional data to perfusion variables offered an incremental prognostic value for patients with an intermediate clinical risk and scheduled intermediate risk surgery. CONCLUSIONS: Integrating information about clinical risk factors, type of surgery, myocardial perfusion and cardiac function allows detailed preoperative risk stratification. Preoperative SPECT provides an incremental prognostic value in intermediate, but not in low-risk surgery. PMID- 17721018 TI - Efficacy of continuous low-dose hANP administration in patients undergoing emergent coronary artery bypass grafting for acute coronary syndrome. AB - BACKGROUND: Low-dose continuous human atrial natriuretic peptide (hANP) administration during cardiac surgery has been reported on previously. In the present study, the efficacy of the therapy during emergent coronary artery bypass grafting (CABG) for acute coronary syndrome (ACS) is investigated. METHODS AND RESULTS: One hundred and twenty-four patients patients undergoing emergent CABG for ACS were divided into 2 groups; a group receiving administration of hANP (hANP group) and a group not receiving hANP infusion (non-hANP group). The postoperative peak levels of creatine kinase-MB were significantly lower in the hANP group as compared with those in the non-hANP group. The incidence of postoperative arrhythmias was also significantly lower in the hANP group as compared with that in the non-hANP group. The postoperative brain natriuretic peptide was significantly lower in the hANP group as compared with that in the non-hANP group until 1 year after the operation. The free-rate of cardiac events after the operation was also significantly higher in the hANP group as compared with that in the non-hANP group. CONCLUSIONS: It is therefore considered that hANP might not only be effective for overcoming some major shortcomings of cardiopulmonary bypass, but also might be effective to attenuate ischemia reperfusion injury, protect the myocardium, have an anti-arrhythmic effect, and suppress left ventricular remodeling. PMID- 17721019 TI - Right ventricular end-diastolic volume in the postoperative care of cardiac surgery patients: a marker of the hemodynamic response to a fluid challenge. AB - BACKGROUND: This study evaluated the right ventricular end-diastolic volume index (RVEDVI) as a marker of the hemodynamic response to a fluid challenge in the postoperative care of cardiac surgery patients. METHODS AND RESULTS: Continuous RVEDVI and other hemodynamic parameters were analyzed during and after 17 fluid challenges with 480-500 ml colloids (5% albumin, fresh frozen plasma or 6% hydroxyethyl starch) given over 30-60 min following cardiac surgery. Changes in stroke volume index (SVI) were assessed to indicate fluid responsiveness. Responders were defined as those who experienced a 10% or greater increase in SVI. Fluid challenges with simultaneous changing of vasoactive agents were excluded. Linear regression analysis between the percentage change in SVI and baseline RVEDVI revealed a statistically significant but weak correlation (r(2)=0.249; p=0.041). Although the baseline RVEDVI was higher in non-responders than in responders (112.4+/-6.1 vs 104.4+/-5.8 ml/m(2); p=0.05), there was a marked overlap of baseline RVEDVI values, which did not allow identification of the threshold value of RVEDVI discriminating responders. CONCLUSIONS: After cardiac surgery, RVEDVI reflected fluid responsiveness only to a limited degree. Patients should not be resuscitated to an absolute RVEDVI alone and empirical fluid challenge should still be required. PMID- 17721020 TI - Characterization of left ventricular filling abnormalities and its relation to elevated plasma brain natriuretic peptide level in acute to chronic diastolic heart failure. AB - BACKGROUND: Although Doppler left ventricular (LV) filling abnormalities have been extensively analyzed in patients with systolic heart failure (SHF), they have not yet been well characterized in patients with acute to chronic diastolic heart failure (DHF) in the light of plasma brain natriuretic peptide (BNP) levels. METHODS AND RESULTS: In 25 patients presenting with acute DHF and 25 with acute SHF, echo Doppler parameters and plasma BNP levels were obtained on admission and in the chronic stage. The mitral E/A ratio was lower in DHF patients than in SHF patients in the acute stage (1.3 +/-0.4 vs 1.8+/-0.9, p<0.05), and in the chronic stage of DHF the ratio decreased with plasma BNP level, but plasma BNP level was still greater than 100 pg/ml in 15 patients (60%). Among patients with DHF the plasma BNP level did not correlate with the mitral E/A ratio or deceleration time (r=0,25, p=NS; r=0,23, p=NS), but did with estimated pulmonary artery systolic pressure (r=0.64, p<0.01). CONCLUSIONS: A restrictive mitral flow velocity pattern is observed in only 25% of patients with DHF, so it is particularly important to recognize pseudonormalization in those with possible DHF. Persistently elevated plasma BNP level is not primarily caused by LV diastolic dysfunction, but by secondary alteration for hemodynamic adjustment (elevated LV end-diastolic pressure) in patients with DHF. PMID- 17721021 TI - Effects of supplemental O2 inhalation on cerebral oxygenation during exercise in patients with left ventricular dysfunction. AB - BACKGROUND: It has been recently reported that cerebral oxyhemoglobin (O(2)Hb) decreases during exercise in nearly 50% of patients with dilated cardiomyopathy. The present study evaluated whether the inhalation of supplemental O(2) diminishes the decrease in cerebral O(2)Hb during exercise. METHODS AND RESULTS: Ten patients with a left ventricular ejection fraction <50% and a clearly observable decrease in cerebral O(2)Hb during preliminary exercise testing underwent 2 additional symptom-limited incremental exercise tests: 1 while breathing room air (control) and the other while breathing 50% O(2). In the latter test, the switch from room air to 50% O(2) was performed, on average, at 43.0+/-14.2 W. Cerebral O(2)Hb was continuously monitored during exercise using near-infrared spectroscopy. In the control exercise test, cerebral O(2)Hb gradually decreased as the work rate increased in all the subjects. When the subjects breathed 50% O(2), this decrease in cerebral O(2)Hb was diminished. The change in cerebral O(2)Hb from rest to peak exercise during the test under 50% O(2) was significantly higher than that during the control test (-0.23 +/-1.89 vs -2.47+/-1.57 micromol/L, p=0.002). Similarly, the change in the cerebral tissue oxygenation index was significantly higher in the test under 50% O(2) (0.45 +/ 4.46 vs -3.33+/-3.06%, p=0.023). CONCLUSIONS: Impaired cerebral oxygenation during moderate to heavy intensity exercise in patients with left ventricular dysfunction can be offset by breathing supplemental O(2). PMID- 17721022 TI - Predictors of congestive heart failure in patients on maintenance hemodialysis. AB - BACKGROUND: Cardiovascular disease is a major cause of death in patients on maintenance hemodialysis (HD). Predictors of congestive heart failure (CHF) events in patients on HD were investigated, focusing on left ventricular (LV) function. METHODS AND RESULTS: One hundred consecutive patients on HD were followed for at least 5 years after index examination performed 1 day after the last HD session. Tests included M-mode and Doppler echocardiography and plasma brain natriuretic peptide (BNP) and hemoglobin (Hb) concentration measurements. Patients with atrial fibrillation or poor echocardiographic images were excluded. Confounding factors included diabetes mellitus (DM), hypertension, age, HD duration, LV fractional shortening, E/A of transmitral flow velocity pattern, Tei index, LV mass index (LVMI), BNP level, Hb, and use of antihypertensive or antiarrhythmic drugs. Six CHF events occurred during 1,703+/-565 days. DM and Hb <10 g/dl were identified as independent predictors of CHF events in a stepwise Cox regression model after DM, LVMI, BNP, and Hb <10 g/dl were selected in the univariate analysis. The hazard ratio (confidence interval) was 10.96 (1.49 80.44) for DM, and 23.00 (2.41-219.76) for Hb <10 g/dl. The estimated hazard across time was constant (T_COV*DM; p=0.726, T_COV*Hb <10 g/dl; p=0.681) by time dependent covariates analysis. CONCLUSION: In patients on maintenance HD, DM and anemia (Hb <10 g/dl), but not echo-derived cardiac function, predicted CHF events. PMID- 17721023 TI - Pulmonary vein antrum not always coaxial to the pulmonary vein: a dimensional pitfall to the circumferential isolation technique. AB - BACKGROUND: The dimensions and electrophysiological characteristics of the antral region of human pulmonary veins (PVs) were investigated. METHODS AND RESULTS: Fifty-five consecutive patients with symptomatic paroxysmal atrial fibrillation underwent PV isolation targeting the PV antrum potentials with a 31 mm multielectrode basket catheter (MBC). The most distal and proximal electrode pairs along the MBC spline where radiofrequency ablation was carried out were identified and the longitudinal distance between those ablation sites (Ld) was measured. When the Ld was > or =6 mm, the PV antrum was defined as noncoaxial. In 56% of the left superior PVs, 42% of the right superior PVs, 63% of the left inferior PVs and 56% of the right inferior PVs, a noncoaxial PV antrum was identified. In each PV, the radiofrequency ablation delivery duration and energy to complete the PV antrum isolation were significantly larger in the PVs with a noncoaxial PV antrum than in those with a coaxial PV antrum. CONCLUSION: The PV antrum is noncoaxial to the PV in >50% of the PVs, a feature that may increase the complexity of the circumferential isolation technique. PMID- 17721024 TI - Electrocardiographic and electrophysiologic characteristics in patients with Brugada type electrocardiogram and inducible ventricular fibrillation: single center experience. AB - BACKGROUND: The study examined the electrocardiographic and electrophysiologic characteristics in relation to programmed ventricular stimulation (PVS)-induced ventricular fibrillation (VF) in patients with Brugada syndrome. METHODS AND RESULTS: Thirty-four patients with a Brugada-type electrocardiogram (ECG) were enrolled. Twelve patients had a type 1 ECG, 12 had a type 2 ECG, and 10 had a type 3 ECG. PVS was performed with up to 2 ventricular premature beats from the right ventricular apex and outflow tract at 2 basic cycle lengths (600 and 400 ms). VF was induced in 17 of 23 (74%) asymptomatic patients and 10 of 11 (91%) symptomatic patients (p<0.05). The 27 patients in whom VF was induced by PVS and 7 patients without inducible VF were followed up for 47.1+/-33.7 months. One sudden death occurred during the follow-up period among asymptomatic patients with inducible VF, and no sudden death occurred among patients without inducible VF. CONCLUSIONS: In conclusion, inducibility of ventricular arrhythmia is high in patients with Brugada syndrome, but it does not correlate with clinical presentation. Few arrhythmic events occur during follow up. However, the present study data suggest that electrophysiologic study-induced VF does not predict arrhythmic events during follow up. PMID- 17721025 TI - Efficacy of coronary venoplasty for left ventricular lead implantation. AB - BACKGROUND: Optimal target vein selection for the pacing lead results in a better outcome, but left ventricular (LV) variability limits this selection. The aim of the present study was to investigate the efficacy of coronary venoplasty for insertion of a LV lead. METHODS AND RESULTS: Transvenous LV lead placement was attempted in 208 consecutive patients from November 2002 to January 2007, with success in 206 patients (99%). Retrospective analysis of the cardiac resynchronization therapy system implantation showed that 4 of the 206 patients (1.9%) required coronary venoplasty for insertion of the pacing lead implant. Using coronary balloon angioplasty catheters of 2.5 mm (2 patients), 3.0 mm (1 patient) and 4.0 mm (1 patient), each target vein was dilated. Of 4 patients, stenoses in 3 were dilated by balloon angioplasty only. However, focal stenosis of 1 patient was not able to be dilated due to severe stenosis. Therefore, part of the lesion was sharpened by rotational atherectomy and the stenosis was successfully dilated. The LV pacing lead could then be inserted and no complications occurred. CONCLUSION: Venoplasty for stenosis was effective in allowing deployment of a LV lead into a target vein in some patients. The safety and complications of the procedure remain unclear. PMID- 17721026 TI - Plasma brain natriuretic peptide levels indicating thromboembolism in very elderly patients with non-valvular atrial fibrillation. AB - BACKGROUND: Assessment of left atrial (LA) function by transesophageal echocardiography is useful for detecting patients with a high risk thromboembolism secondary to atrial fibrillation (AF). A recent study showed that the atrium is the main source of brain natriuretic peptide (BNP) in AF patients without overt heart failure. The purpose of this study was to assess the possible relationship between LA function and plasma BNP levels in very elderly patients with non-valvular AF. METHODS AND RESULTS: Seventy-four consecutive patients with chronic non-valvular AF (aged, 82+/-6 years) underwent transthoracic and transesophageal echocardiography and measurement of plasma BNP. Thirteen AF patients who had a history of cerebral embolism or echocardiographic evidence of thrombus (TE+ group) were compared with 61 AF patients who had no such complications (TE- group). The TE+ group demonstrated a lower LA appendage (LAA) velocity and higher plasma BNP level than the TE- group. Assessment of variables by multiple logistic regression analysis revealed that BNP was a significant predictor of thromboembolism. There was a significant negative correlation between the plasma BNP level and the LAA peak flow velocity. CONCLUSIONS: The present findings would suggest the usefulness of measuring plasma BNP to detect very elderly non-valvular AF patients at high risk for thromboembolism. PMID- 17721027 TI - Circulating levels of heart-type fatty acid-binding protein in a general Japanese population: effects of age, gender, and physiologic characteristics. AB - BACKGROUND: Serum heart-type fatty acid-binding protein (H-FABP) has been widely used as a marker of cardiac myocyte injury. This study was carried out to examine the relationships of H-FABP levels with age, gender, and other physiologic characteristics in a large population of community-dwelling residents. METHODS AND RESULTS: Serum H-FABP levels were measured in 2,099 subjects who received an annual health check-up (age 40-87 years). The relationships between H-FABP and blood pressure, laboratory data, electrocardiogram (ECG) findings, and lifestyle factors were cross-sectionally analyzed. Mean H-FABP values were significantly higher in men than in women. Serum H-FABP levels were increased with aging significantly. Both the multivariate regression and multiple logistic regression analyses indicated that serum H-FABP levels were independently affected by age, body mass index, creatinine clearance, and ECG abnormality score. CONCLUSION: Serum H-FABP levels were affected by age, gender, obesity, renal function, and ECG abnormality in a large group of volunteers. These effects should be taken into account in determining appropriate reference values for H-FABP. In addition, high serum H-FABP levels may represent latent cardiac injury and have important clinical implications. PMID- 17721028 TI - Diversity of the elevation of serum cardiac troponin I levels in patients during their first visit to the emergency room. AB - BACKGROUND: Although measurement of serum creatine kinase levels, as well as myoglobin levels, has been used for screening patients with acute coronary syndrome (ACS), the specificity of both is low. Measurement of cardiac troponin levels is now extensively used for the diagnosis of ACS because of their superior cardiac specificity. However, troponin levels are reportedly elevated not only in patients with ACS but also in those with other diseases. METHODS AND RESULTS: The clinical characteristics of 1,023 patients (mean age: 63.5+/-16.3 years; males: 665, females: 358) whose serum cardiac troponin I (cTnI) levels had been measured at the initial visit to the emergency room of Toyota Memorial Hospital between April 2004 and March 2005 were retrospectively analyzed. A positive elevation of cTnI was defined as cTnI > or =0.03 ng/ml. There were 432 patients (42.2%) with positive cTnI levels. The cTnI levels (8.48+/-2.64 ng/ml) in patients with acute myocardial infarction (AMI) were greater than those (0.25+/-0.07 ng/ml) in patients with unstable angina pectoris (AP), as well as those (0.04+/-0.01 ng/ml) in patients with stable AP. In terms of the diagnosis of AMI, the sensitivity was high enough (94.6%), but its specificity was relatively low (61.9%). Furthermore, the differentiation between AMI and unstable AP by the cTnI value alone was impossible. The cTnI levels were elevated in patients with a variety of diseases other than ACS, including heart failure, cardiomyopathies, myocarditis, renal failure, tachyarrhythmias, and pulmonary embolism. CONCLUSIONS: Elevation of the cTnI level is frequently observed in patients in the emergency room with common diseases other than ACS. PMID- 17721029 TI - Elevated LDL-cholesterol level predicts diabetes in centrally obese women but not men: relative roles of insulin resistance and central obesity. AB - BACKGROUND: The aim was to investigate the sex-specific effect of hypercholesterolemia interacting with abdominal obesity (AO) in predicting Type 2 diabetes mellitus (DM). The 3,048 participants (aged > or =28 years) were free of DM at baseline, a representative sample of Turkish adults and were evaluated prospectively. METHODS AND RESULTS: As cut-off points for AO were used > or =95 cm in men and > or =91 cm in women, and for hypercholesterolemia > or =5.2 mmol/L. Diabetes was diagnosed using criteria of the American Diabetes Association. Four groups were formed at baseline: Group I subjects had neither AO nor hypercholesterolemia (33.3%), Group II subjects had AO only (27.6%), Group III subjects had hypercholesterolemia only (17.8%), and Group IV subjects had AO combined with hypercholesterolemia (21.3%). Over a mean of 5.9 years, DM developed in 103 women and 116 men. An age-adjusted relative risk (RR) by logistic regression for DM in the 4 groups, using AO as a reference group, disclosed an RR of 1.88 (95% confidence interval 1.14; 3.09) in women and an insignificant RR 1.29 in men (women were predicted to be 1.46 times more likely to develop DM). Hypercholesterolemia alone did not differ significantly from Group I in its ability to predict diabetes. An elevated level of low-density lipoprotein (LDL)-cholesterol (C) (> or =3.4 mmol/L) was delineated as the element associated with diabetes in hypercholesterolemia by multiple logistic regression. The identification of 48 participants with familial-combined hyperlipidemia phenotypes alone could not account for most of the centrally obese and hypercholesterolemic women developing DM. CONCLUSION: It was suggested that a diminished effectiveness of insulin resistance in centrally obese Turkish women (but not men) might predispose them to an elevation in LDL concentrations, while other features of visceral adiposity still predispose them to DM. In summary, an elevated LDL-C level interacts with AO in Turkish women to enhance the development of diabetes. PMID- 17721030 TI - Thirty-day outcomes of direct carotid artery stenting with cerebral protection in high-risk patients. AB - BACKGROUND: Implantation of a carotid artery stent after predilation is a standard approach in the endovascular treatment of carotid artery stenoses. Stenting without predilation may be an alternative approach in a certain subset of patients. The present prospective, single-center registry was designed to evaluate the feasibility and safety of direct carotid artery stenting (DCAS) in high-risk patients. METHODS AND RESULTS: Symptomatic patients with stenosis >50% and asymptomatic patients with stenosis >70% were eligible for enrolment. Criteria for high-risk patients included: need or history of open heart surgery, history of myocardial infarction, multivessel coronary artery disease, left ventricular dysfunction (ejection fraction < or =40%), severe pulmonary or renal disease, significant contralateral carotid disease, previous endarterectomy, and age > or =80 years. All procedures were performed using a filter protection device. Patients underwent complete clinical examination before and after DCAS and at 30-day follow-up. A total of 83 consecutive patients (45 males, 68+/-9 years, 33% symptomatic) underwent 100 procedures and 103 stents were deployed successfully. The technical success rate of stenting was 100%. Predilation of carotid stenosis was necessary in 1 (1%) procedure. Carotid-artery stenoses before and after DCAS were 80+/-9% and 7+/-9%, respectively. The median fluoroscopic time for DCAS was 7 min. The overall rate of in-hospital major adverse cerebrovascular events (death, stroke, myocardial infarction) was 5% (2 minor strokes, 3 transient attacks). There was 1 (1%) minor stroke within the 30 day follow-up. CONCLUSION: DCAS is feasible and can be performed with an acceptable risk in high-risk patients. PMID- 17721031 TI - Evaluation of pharmacological modulation of nitroglycerin-induced impairment of nitric oxide bioavailability by a catheter-type nitric oxide sensor. AB - BACKGROUND: The present study aimed to elucidate the effect of long-term treatment with nitroglycerin (NTG) on the bioavailability of nitric oxide (NO) examined by a catheter-type NO sensor. The study also examined whether these effects could be modified by an antioxidant, an angiotensin converting enzyme inhibitor, or an angiotensin II type 1 receptor antagonist (ARB). METHODS AND RESULTS: Male New Zealand rabbits were treated for 7 days with NTG patches, either alone or in combination with tempol, enalapril, or valsartan (ARB). The plasma NO concentration was measured with the catheter-type NO sensor. The plasma peroxynitrite concentration was measured by enzyme-linked immunosorbent assay. An increase in plasma NO concentration in response to acetylcholine (ACh) were significantly attenuated in the NTG-treated group as compared with the control. Plasma peroxynitrite concentration in NTG-treated group was significantly higher as compared with the control. The negative effects of NTG were significantly suppressed by the co-treatment with tempol, enalapril or valsartan. CONCLUSIONS: Chronic treatment of rabbits with NTG elicits the impairment of the ACh stimulated NO production. In addition, the negative effects of NTG might be prevented by the co-treatment with drugs attenuating nitrosative stress. PMID- 17721033 TI - Ruptured aneurysm of the sinus of Valsalva with Wildervanck syndrome (cervico oculo-acoustic syndrome), blepharoptosis and short stature: case report. AB - A 62-year-old woman was admitted to hospital because of nausea. A grade 5/6 continuous murmur was audible near the left sternal border at the second intercostal space. Chest X-ray showed cardiomegaly and bilateral pleural effusion. She was diagnosed as heart failure and a diuretic was prescribed. After remission of the heart failure, echocardiography showed shunt flow from the right coronary cusp to the right ventricle. Aortography revealed that an aneurysm of the right coronary sinus of Valsalva had ruptured into the right ventricle. Coronary angiography revealed a single coronary artery. Chest computed tomography revealed persistent left superior vena cava. Surgical repair was carried out and the patient made an uneventful recovery. In addition to these cardiovascular abnormalities, she had Wildervanck syndrome (Klippel-Feil syndrome, Duane syndrome and sensorineural hearing disturbance), blepharoptosis and short stature. This rare combination has not been reported previously. PMID- 17721032 TI - Effects of bradykinin on aortic endothelial function in apoe-knockout mice with chronic Chlamydia pneumoniae infection. AB - BACKGROUND: Impaired muscarinic receptor-mediated vasodilation is an important feature of early atherosclerosis. Earlier studies on apolipoprotein E-knockout mice (apoE-KO) mice suggested adverse effects of Chlamydia pneumoniae infection on the endothelial vasomotor responses of aortas to the muscarinic agonist methacholine. Using additional aorta samples the present study investigated the responses to bradykinin. METHODS AND RESULTS: ApoE-KO mice were repeatedly inoculated with either Chlamydia pneumoniae (C. pneumoniae) or saline. At 2, 6, and 10 weeks after the first inoculation, precontracted aorta rings from both groups were exposed to bradykinin in the absence and presence of L-NAME and diclofenac. In noninfected animals, the vasomotor responses to bradykinin were similar at all timepoints (p>0.5). Compared with noninfected animals, the responses in infected animals tended to increase through the study period (p<0.05 at 10 weeks). Although diclofenac and L-NAME had no effect in noninfected mice, they inhibited the responses to bradykinin in infected mice at 6 and, more markedly, 10 weeks (p<0.05 for both). CONCLUSION: Bradykinin stimulation of aorta endothelium from C. pneumoniae-infected apoE-KO animals appears to activate compensatory kinin receptor-related mechanisms that could involve nitric oxide and vasorelaxing prostanoids. Although the precise molecular mechanisms require further investigation, one could speculate that strategies increasing bradykinin availability might reverse the arterial dysfunction during chronic infectious disease. PMID- 17721034 TI - Three fatal cases of rapidly progressive infective endocarditis caused by Staphylococcus aureus: one case with huge vegetation. AB - Staphylococcus aureus (S. aureus) infective endocarditis (IE) is a severe disease with a high mortality despite intensive therapy. Three cases of S. aureus IE had a rapidly progressive fatal clinical course despite intensive antimicrobial therapy. One case was methicillin-sensitive S. aureus IE, which formed rapidly growing a huge vegetation on a prosthetic mitral valve, complicated with multiple systemic emboli. The other 2 cases were methicillin-resistant S. aureus IE without any predisposing heart disease. PMID- 17721035 TI - Coronary flow characteristics of multiple coronary artery-left ventricular microfistulae in young monozygotic twins. AB - Coronary artery multiple fistulae of the left ventricular chamber are extremely rare congenital malformations. We report on 13-year-old monozygotic twin brothers who have identical abnormalities of coronary flow reserve as well as the same morphological findings of multiple coronary fistulae of the 3 major coronary arteries to the left ventricular chamber. The left circumflex coronary artery (LCX) had abundant fine communications with the left ventricular chamber and had a higher flow rate than the left anterior-descending coronary artery. The coronary flow reserve obtained from the LCX was lower than the normal value matched for the same age group. The increased shunt flow resulted in enlargement of the left ventricular chamber. This is the first report of coronary flow characteristics in children with multiple coronary fistulae. PMID- 17721036 TI - Robotically assisted multivessel minimally invasive direct coronary artery bypass grafting with the use of bilateral internal thoracic arteries. AB - This case report presents the robotically assisted multivessel minimally invasive direct coronary artery bypass grafting (MIDCAB) technique using the bilateral internal thoracic arteries. A 54-year-old man with multivessel coronary artery disease was considered eligible for a robotically assisted myocardial revascularization. The bilateral internal thoracic arteries were harvested completely in a totally skeletonized fashion through three 1-2-cm-long incisions on the left thoracic wall. A small left anterior thoracotomy was then performed. The left internal thoracic artery was anastomosed to the left anterior descending coronary artery, and the composite radial artery graft from the right internal thoracic artery was sequentially anastomosed to the first diagonal branch, the obtuse marginal branch, and the distal right coronary artery on the beating heart without cardiopulmonary bypass. The harvesting time of the grafts was 66 min, and the total operative time was 5 h 58 min. Postoperative angiography revealed that all grafts were widely patent. The postoperative course was uneventful, and the patient was discharged 10 days after the operation. Robotically assisted MIDCAB using the bilateral thoracic arteries is a safe and effective means of myocardial revascularization for patients with multivesssel disease. PMID- 17721037 TI - Transferring images via the wireless messaging network using camera phones shortens the time required to diagnose acute coronary syndrome. AB - BACKGROUND: Clear images can be sent via e-mail using camera phones. We examined whether camera phones are useful to transmit electrocardiogram (ECG) images. METHODS AND RESULTS: ECG images were taken of 20 patients suspected to have acute coronary syndrome. Ten images were sent to a cardiologist by fax. The other 10 images were transmitted using a camera phone. The total time elapsed between image transmission to diagnosis by cardiologists was shorter in the camera phone group than in the fax group. CONCLUSIONS: ECG image transmission by camera phone can be efficiently used in the diagnosis of acute coronary syndrome. PMID- 17721038 TI - C-Reactive protein cutoff-point of 0.65 mg/L may be appropriate not only as a component of metabolic syndrome but also as a risk predictor of cardiovascular disease. PMID- 17721040 TI - The Wnt/beta-catenin signaling pathway as a target in drug discovery. AB - The cell signaling cascades provoked by Wnt proteins (the Wnt signaling pathways), which are well conserved through evolution, play crucial roles to maintain homeostasis of a variety of tissues such as skin, blood, intestine, and brain, as well as to regulate proliferation, morphology, motility, and fate of cells during embryonic development. Among these pathways, the signal transduction through beta-catenin (the Wnt/beta-catenin signaling pathway) has been most intensively studied because this signal regulates the expression of a number of genes essential for cell proliferation and differentiation and also this pathway is perturbed in a number of diseases such as cancers, bone diseases, and cardiovascular diseases. However, there is no therapeutic agents that can selectively modulate the Wnt/beta-catenin signaling pathway, although some existing drugs (e.g., non-steroidal anti-inflammatory drugs, vitamins, and imatinib mesylate) have been suggested to inhibit this pathway. Here we provide an overview of the Wnt/beta-catenin signaling pathway: its roles in physiology and pathology and the possibility as a target in development of new drugs. PMID- 17721041 TI - Edaravone preserves coronary microvascular endothelial function after ischemia/reperfusion on the beating canine heart in vivo. AB - We examined whether edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, exerts its protective effect on coronary microvessels after ischemia/reperfusion (I/R) in vivo. Ninety-minute coronary occlusion followed by reperfusion was performed in 16 open-chest dogs with and without edaravone administration. Coronary small artery (> or = 100 microm in size) and arteriolar (< 100 microm) vasodilation, in the presence of endothelium-dependent (acetylcholine) or -independent (papaverine) vasodilators, was directly observed using intravital microscopy before and after I/R. I/R impaired microvascular vasodilation in response to acetylcholine, whereas administration of edaravone preserved the response in microvessels of both sizes, but to a greater extent in the coronary small arteries. No significant changes were noted with papaverine administration. In the edaravone group, the fluorescent intensity from reactive oxygen species (ROS) was lower, whereas nitric oxide (NO) intensity was higher relative to controls in the microvessels of the ischemic area. In conclusion, edaravone preserves coronary microvascular endothelial function after I/R in vivo. These effects, which were NO-mediated, were attributed to the ROS scavenging properties of edaravone. PMID- 17721042 TI - Inhibition of cell growth and induction of apoptosis via inactivation of NF kappaB by a sulfurcompound isolated from garlic in human colon cancer cells. AB - Compounds such as S-allylmercaptocysteine, diallyl disulfide, and S-trityl-L cysteine isolated from garlic have been known to be effective in chemoprevention. Nuclear transcription factor-kappaB (NF-kappaB) has been known to be an implicated factor in apoptotic cell death of several cancer cells. In this study, we investigated whether a sulfurcompound (named thiacremonone) isolated from garlic could modulate NF-kappaB activity and thereby induce apoptotic cell death of colon cancer cells. Treatment with different concentrations (30 - 150 microg/ml) of thiacremonone for various periods (0 - 48 h) inhibited colon cancer cell (SW620 and HCT116) growth followed by induction of apoptosis in a dose dependent manner. We also found that thiacremonone modulated tumor necrosis factor-alpha (TNF-alpha) and tetradeanoyl phorbol acetate (TPA)-induced NF-kappaB transcriptional and DNA binding activity. Moreover, thiacremonone suppressed NF kappaB target anti-apoptotic genes (Bcl-2, cIAP1/2, and XIAP) and inflammatory genes (iNOS and COX-2), whereas it induced apoptotic genes (Bax, cleaved caspse 3, and cleaved PARP) expression. These results suggest that a novel sulfurocompound from garlic inhibited colon cancer cell growth through induction of apoptotic cell death by modulating of NF-kappaB. PMID- 17721043 TI - Bone formation with the combination of simvastatin and calcium sulfate in critical-sized rat calvarial defect. AB - Simvastatin, a cholesterol synthesis inhibitor, enhances BMP2 expression in osteoblasts. The purpose of the present study was to examine whether simvastatin stimulates bone regeneration when combined with calcium sulfate as a carrier. Critical-sized bone defects in rat calvaria were treated with calcium sulfate or with combination of 1 mg simvastatin and calcium sulfate. In the combination group, although the least amount of bone formation with intense soft tissue inflammation was observed at 2 and 4 weeks, remarkable bone formation was evident at 8 weeks. Conclusively, the combination of simvastatin and calcium sulfate stimulated bone regeneration in spite of the inflammatory response. PMID- 17721044 TI - Identification of proteins that regulate radiation-induced apoptosis in murine tumors with wild type p53. AB - In this study, we investigated the molecular factors determining the induction of apoptosis by radiation. Two murine tumors syngeneic to C3H/HeJ mice were used: an ovarian carcinoma OCa-I, and a hepatocarcinoma HCa-I. Both have wild type p53, but display distinctly different radiosensitivity in terms of specific growth delay (12.7 d in OCa-I and 0.3 d in HCa-I) and tumor cure dose 50% (52.6 Gy in OCa-I and > 80 Gy in HCa-I). Eight-mm tumors on the thighs of mice were irradiated with 25 Gy and tumor samples were collected at regular time intervals after irradiation. The peak levels of apoptosis were 16.1 +/- 0.6% in OCa-I and 0.2 +/- 0.0% in HCa-I at 4 h after radiation, and this time point was used for subsequent proteomics analysis. Protein spots were identified by peptide mass fingerprinting with a focus on those related to apoptosis. In OCa-I tumors, radiation increased the expression of cytochrome c oxidase and Bcl2/adenovirus E1B-interacting 2 (Nip 2) protein higher than 3-fold. However in HCa-I, these two proteins showed no significant change. The results suggest that radiosensitivity in tumors with wild type p53 is regulated by a complex mechanism. Furthermore, these proteins could be molecular targets for a novel therapeutic strategy involving the regulation of radiosensitivity. PMID- 17721045 TI - Serotonin-induced ion channel modulations in mesenteric artery myocytes from normotensive and DOCA-salt hypertensive rats. AB - Although serotonin (5-hydroxytryptamine, 5-HT) has been found to be a potent vasoconstrictor, a pivotal role of 5-HT in the control of appetite and mood control by the modulation of neuronal synapse has also been proposed. Selective 5 HT reuptake inhibitors (SSRIs) are frequently used to suppress appetite and treat depressive disorder, and the target protein of SSRIs is the 5-HT transporter (5 HTT) in the neuronal synapse. However, SSRIs may increase the free 5-HT concentration in circulating blood because platelets and vascular smooth muscles express functional 5-HTT. In addition, enhanced vasoactive action of 5-HT and alterations in 5-HT receptor subtypes have been reported in some types of hypertension. Therefore, we can infer that the use of drugs such as SSRIs in some hypertensive patients is potentially risky. Altered functional expression of ion channels in vascular smooth muscle is suggested to be a mechanism for the enhanced vasoconstriction by vasoactive agonists, including 5-HT. In this brief review, we compared the electrophysiological properties of mesenteric artery myocytes and their modulation by 5-HT between sham-operated control and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. PMID- 17721046 TI - Stepped assessment of gastric emptying of a solid meal using the (13)C-octanoic acid breath test. AB - The (13)C-octanoic acid breath test is widely used for evaluating gastric emptying of solids. Since the results of this test are influenced by multiple factors such as the time required to grind the solid meal into smaller particles, the gastroduodenal transport time of the ground meal, and the time required for bowel drug absorption and drug dispersion, the administration of a test meal by the oral route alone cannot result in an accurate measurement of the complicated process of emptying the stomach of solids. The aim of the present study was to evaluate each phase of gastric emptying of solids by varying the administration route of the test meal. Six healthy male volunteers (mean age: 33.2 yr) participated in the study. The test meal consisted of a bowl of rice topped with a mixture of boiled chicken and eggs admixed with 100 mg of (13)C-octanoic acid (total: 273 kcal). All subjects were given the test meal by each of the following three methods: 1. Normal oral intake of the test meal, 2. Feeding of the ground test meal through a nasogastric tube, 3. Feeding of the ground test meal through a duodenal tube. For each set of examinations, the mean residence time (MRT), half-emptying time (T(1/2)), gastric emptying coefficient (GEC), lag phase (L breath), and measured maximum (13)C excretion time (Tmax-measured) were calculated. The data was analyzed to determine the time for each phase of gastric emptying as follows: mean grinding time (MGT) = MRT(oral) - MRT(nasogastric), mean gastroduodenal transport time (MGDTT) = MRT(nasogastric) - MRT (nasoduodenal). Data was expressed as the mean +/- SE. The values of the parameters of MGT were 0.82 +/- 0.50 hr (MRT), 0.64 +/- 0.18 hr (T(1/2)), 0.51 +/ 0.24 hr (L-breath), -0.45 +/- 0.30 hr (GEC), and 49.2 +/- 8.0 min (Tmax measured). The values of the parameters of MGDTT were 0.87 +/- 0.38 hr (MRT), 0.26 +/- 0.29 hr (T(1/2)), 0.92 +/- 0.36 hr (L-breath), 0.55 +/- 0.23 hr (GEC), and 63.33 +/- 8.16 min (Tmax-measured). The times required for the drug absorption and disposition were 1.60 0.20 hr (MRT), 1.03 +/- 0.24 hr (T(1/2)), 0.10 +/- 0.08 hr (L-breath), 3.72 +/- 0.46 hr (GEC), and 19.67 +/- 2.11 min (Tmax measured). By varying the administration route of a test meal containing (13)C octanoic acid, we may be able to assess each phase of the emptying of gastric solids in detail, thus leading to a better understanding of gastroduodenal motility. PMID- 17721047 TI - L-arginine-induced current in portal venous smooth muscle cells. AB - In our previous report, we showed that L-arginine induced depolarization of smooth muscle cells of the rat portal vein with an increased contraction. To clarify the ionic mechanism of the membrane depolarization, the effect of L arginine on the holding current was studied in freshly isolated smooth muscle cells of the rat portal vein. The whole-cell patch-clamp technique was used, with the membrane potential held at -60 mV. In the presence of Na+ in the perfusate, L arginine 10 mM induced an inward current in about 50% of the cells. In Na+ deficient perfusate, L-arginine 10 mM increased the amplitude of the inward current in a Na+ concentration-dependent manner. BCH, an inhibitor of the Na+ dependent amino acid transporter, ceased the L-arginine-induced current. These results indicate that L-arginine induces an inward current via Na+-dependent mechanisms in rat portal venous smooth muscle cells. PMID- 17721048 TI - Assessment of the anatomical relationship between the arcuate eminence and superior semicircular canal by computed tomography. AB - The anatomical relationship between the arcuate eminence (AE) and the superior semicircular canal (SSC) was examined by computed tomography (CT) in 52 petrous bones of 26 patients. After acquiring volume data by multidetector CT, 1-mm thick oblique bone window images perpendicular to the SSC were obtained from the axial images. The distances between the AE and the SSC, and the SSC and the superior surface of the petrous bone were measured. The AE corresponded exactly with the SSC in only 2/52 petrous bones, and corresponded well in 7/52. The AE was lateral to the SSC in 25/52 cases, medial to the SSC in 6/52 cases, intersected in 3/52 cases, and was indiscernible in 9/52 cases. The distance between the SSC and the petrous surface was 0 mm in 45/52 petrous bones, 1 mm in 5/52, 2 mm in 1/52, and 3 mm in 1/52. The SSC typically does not correspond exactly with the AE, and is generally located just under the surface of the petrous bone. Planning of the middle cranial fossa approach requires location of the SSC by CT. PMID- 17721049 TI - Efficacy of temozolomide is correlated with 1p loss and methylation of the deoxyribonucleic acid repair gene MGMT in malignant gliomas. AB - Promoter methylation of the deoxyribonucleic acid (DNA) repair gene, O(6) methylguanine-DNA methyltransferase (MGMT), is associated with improved outcome of patients with glioblastoma multiforme and anaplastic astrocytoma treated with temozolomide (TMZ). Molecular genetic analysis of loss of heterozygosity (LOH) of 1p, 19q, or 10q, p53 mutation, and MGMT promoter methylation was performed in 44 assessable tumor specimens obtained from 46 patients with recurrent malignant gliomas, including 21 with glioblastoma multiforme, 17 with anaplastic astrocytoma, and eight with anaplastic oligoastrocytoma, which have heterogeneous features and variable histological diagnosis, to assess the correlation with the response to TMZ. LOHs of 1p and 19q, and MGMT promoter methylation showed positive correlations with the clinical response to TMZ therapy (p < 0.005, 0.05, and 0.05, respectively; Fisher's exact test). In addition, LOH of 1p and MGMT promoter methylation were associated with longer progression-free survival (p < 0.05 and 0.05, respectively; Cox regression analysis). LOH of 1p in the heterogeneous population of malignant gliomas may be one of the important factors besides MGMT methylation that predict better outcome in patients treated with TMZ. PMID- 17721050 TI - Ruptured fusiform aneurysm of the proximal anterior cerebral artery (A1 segment). AB - A 42-year-old man presented with a ruptured fusiform aneurysm of the proximal anterior cerebral artery (A(1) segment) manifesting as sudden onset of severe headache. Brain computed tomography revealed subarachnoid hemorrhage in the basal cisterns, and left carotid angiography demonstrated a fusiform aneurysm of the left A(1) segment. He underwent surgery via the left pterional approach. The left A(1) segment exhibited a fusiform configuration. Adequate development of the anterior communicating artery was confirmed. Trapping of the aneurysm was performed. The aneurysm was associated with atherosclerotic changes. The postoperative course was uneventful, and the patient was discharged without neurological deficits 1 month after surgery. Fusiform aneurysm of the A(1) segment is quite rare, and tends to bleed, so must be treated. The atherosclerotic origin indicates long-term follow up to identify subsequent lesions. PMID- 17721051 TI - Stenosis of the proximal external carotid artery in an adult with moyamoya disease: moyamoya or atherosclerotic change? AB - A 55-year-old woman presented with moyamoya disease manifesting as recurrent transient ischemic attacks despite taking aspirin and antihypertensive agent. Angiography showed the characteristic angiographic appearance with bilateral internal carotid artery occlusion and abnormal collateral vessels. Left external carotid angiography demonstrated moderate stenosis of the proximal external carotid artery (ECA). A self-expandable stent was successfully placed in the left ECA to improve ipsilateral cerebral perfusion. The patient had an uneventful outcome after a 1-year follow up. Involvement of the proximal ECA is very unusual in moyamoya disease, and might result from hemodynamic stress or degenerative atherosclerosis. Revascularization procedures for stenoses of proximal ECA may improve cerebral perfusion in patients with moyamoya disease. PMID- 17721052 TI - Atypical growth pattern of a meningioma in an adult. AB - A 49-year-old woman presented with a rare atypical growth pattern of meningioma without evidence of dural attachment manifesting as chronic headache associated with transient paresthesia and left motor disorders. On admission, neurological examination showed no abnormalities. Magnetic resonance (MR) imaging revealed a right temporo-parieto-occipital lesion, which appeared to involve the subdural space and filling the cortical sulci. The lesion caused peritumoral white matter edema. The tumor appeared hypointense on T(1)-weighted and hyperintense on T(2) weighted MR images, with homogeneous enhancement after contrast administration. A biopsy of the lesion was performed. Histological examination indicated that the lesion was a meningioma. Intraparenchymal meningiomas should be considered in the differential diagnosis of intraaxial lesions in patients of any age. PMID- 17721053 TI - Meningioma in the posterior fossa without dural attachment. AB - A 14-year-old boy presented with a very rare meningioma in the posterior cranial fossa without dural attachment. Magnetic resonance imaging revealed a 3-cm, well circumscribed, heterogeneously enhanced, round mass without dural tail sign in the right side of the posterior fossa. Right vertebral angiography revealed very faint tumor staining supplied by the right posterior inferior cerebellar artery. Total removal of the tumor was performed. Intraoperatively, the mass exhibited no attachment to the dura mater, cerebellar parenchyma, or choroid plexus, but was firmly attached to the arachnoid tissue near the foramen of Luschka. Histological and immunohistochemical studies established the diagnosis of meningothelial meningioma (World Health Organization grade I). PMID- 17721054 TI - Dura-based giant intracranial schwannoma in the middle fossa. AB - A 49-year-old female presented with a rare giant schwannoma arising from the dura mater of the middle fossa manifesting as loss of left visual acuity. Magnetic resonance imaging revealed a heterogeneously enhanced giant mass in the left middle fossa. Surgery via the transsylvian approach confirmed the origin of the tumor between the left internal carotid artery and the trigeminal nerve in the lateral wall of the cavernous sinus. Elongated abducens nerve was confirmed, but no tumor adhesion to the abducens nerve was found. The tumor was closely attached to the dura mater of the middle fossa and the lateral wall of the cavernous sinus. The histological diagnosis was schwannoma. Both left oculomotor and abducens nerve pareses occurred immediately after the operation but gradually resolved over 3 months. The operative findings indicated that this schwannoma may have arisen from the meningeal branch of the trigeminal nerve in the dura mater of the middle fossa. PMID- 17721055 TI - Atypical cervical astrocytoma manifesting as occipitalgia. AB - A 23-year-old female presented with chronic occipitalgia without signs of increased intracranial pressure followed by worsening headache and slight gait unsteadiness. Cerebral magnetic resonance (MR) imaging showed no corresponding lesions. Cervical MR imaging revealed a cervical intramedullary tumor. Intraoperatively the subpial tumor was found to stretch the 3rd-5th dorsal nerve roots posteriorly, which was thought to cause the intolerable headache. Total tumor resection was achieved without requiring myelotomy using electrophysiological monitoring with somatosensory and motor evoked potentials. Histological examination identified diffuse astrocytoma. Postoperatively the headache had completely resolved. Cervical astrocytoma of subpial location is a very rare cause of headache in adults. The subpial location enables surgical extirpation because minimal or no myelotomy is needed. PMID- 17721056 TI - Acute lymphocytic leukemia recurring in the spinal epidural space. AB - A 27-year-old man presented with a very rare spinal epidural mass associated with recurrence of acute lymphocytic leukemia (ALL) manifesting as acute progressive neurological deficits. The patient presented with shoulder pain and ambulatory difficulties 3 years after remission of ALL treated by bone marrow transplantation. Magnetic resonance imaging revealed an epidural mass extending from C-7 to T-3, which compressed the cord and extended to the intervertebral foramen along the roots. After decompression surgery, the symptoms dramatically improved. Histological examination showed clusters of immature lymphocytes consistent with recurrence of leukemia, so chemotherapy and radiation therapy were carried out. At 1 year after the operation, no local mass expansion or systemic progression of leukemia had occurred. Leukemic mass must be considered in the differential diagnosis of spinal epidural mass, even in patients with ALL. PMID- 17721057 TI - Duraplasty in the posterior fossa using a boat-shaped sheet of expanded polytetrafluoroethylene. AB - Application of sutures between expanded polytetrafluoroethylene (ePTFE) dural substitutes and the dura mater is often frustrating in posterior fossa surgery because of the difficulty in holding the elastic graft in a deep and narrow field. To resolve this problem, we have developed a boat-shaped graft made from a triangular ePTFE sheet by pinching each angle using a suture. Formation of standing edges of the sheet facilitates holding of the flaps for secure and more rapid suturing than the conventional approach using a flat sheet. PMID- 17721058 TI - A validation study of devices designed to reduce loads in provision of care: whether these assistive devices are used, or not, and whether work posture is appropriate or not. AB - Our country already faces an aging society, but many care workers suffer from work-related musculoskeletal disorders and assistive devices have not been adopted in care-work sites. In order to evaluate the effectiveness of assistive devices, we conducted a study on care work-load; whether the assistive devices are used or not, and whether work posture is appropriate or not, on five female healthcare workers by measuring surface electromyography (SEMG) of biceps brachii, the trapezius (upper extremity) and lumbar paraspinals between L3 and L4 (low back), and the trunk inclination angle (TIA). Moreover, subjective evaluations both by the caregivers and also the care receivers were verified. The caregivers were asked to rate perceived exertion using the Borg scale and the care receiver was asked to rate dissatisfaction. Work condition 1: Repositioning of a supine patient towards the head of bed. Work condition 2: Transferring a patient from sitting on the bed to sitting in a wheelchair. Under the two work conditions there were five set tasks in which subjects used or did not use the assistive devices and worked with or without the appropriate procedure and posture. The representative value adopted was the 95 percentile value. SEMG: Under both work conditions and at all measurement sites, we observed the statistically significant effectiveness of the appropriate procedure and posture as compared to manual handling. When the assistive devices were used improperly, or in work with low bed height, there was no reduction in workloads on the upper extremities. TIA: In both work conditions we observed statistically significant effectiveness of the appropriate procedure and posture as compared to not only manual handling but also working with improper assistive devices and with low bed heights. Findings of the subjective evaluations: The caregiver's perceived exertion and care receiver's dissatisfaction, showed statistical significance in satisfaction with the appropriate procedure and posture as compared to manual handling. Therefore, to reduce workload, and prevent work-related musculoskeletal disorders of caregivers, it is necessary not only to provide assistive devices but also to supervise the proper procedures and work postures and to improve the work environment. PMID- 17721059 TI - Investigation of postural hypotension due to static prolonged standing in female workers. AB - The "Just-in-Time system" improves productivity and efficiency through cost reduction while it makes workers work in a standing posture. The aim of this study was to investigate the prevalence of postural hypotension in females during prolonged standing work, and to discuss preventive methods. Twelve female static standing workers (mean age+/-standard deviation; 32+/-14 yr old), 6 male static standing workers (30+/-4 yr old), 10 female walking workers (27+/-7 yr old) and 9 female desk workers (31+/-5 yr old) in a certain telecommunications equipment manufacturing factory agreed to participate in this study. All participants received an interview with an occupational physician, and performed the standing up test before working and ambulatory blood pressure monitoring (ABPM) while working. Although the blood pressure of the standing up test did not differ among the groups, mean pulse rates on standing up significantly increased in every group. Hypotension rates in the female standing workers' group by ABPM were 9 persons of 12 participants (75%) for systolic blood pressure (SBP), and were 11 persons of 12 participants (92%) for diastolic blood pressure (DBP). There were significantly higher than those in the female desk workers' group, none of 9 participants (0%) for SBP and 2 of 9 participants (22%) for DBP. The hypotension rates both male standing and female walking worker groups did not differ. Because all 8 workers who were found to have postural hypotension by the standing up test had decreased SBP and/or DBP by ABPM, it is suggested that persons at high risk of postural hypotension during standing work could be screened by the standing up test. The mechanism of postural hypotension may be a decrease of venous return due to leg swelling, and neurocardiogenic or vasovagal response. Preventing the congestion of the lower limbs by walking, managing standing time and wearing elastic hose to keep the amount of the venous return could prevent postural hypotension during prolonged standing work. PMID- 17721060 TI - Development of a mental health action checklist for improving workplace environment as means of job stress prevention. AB - An action checklist for improving the workplace environment by means of enhancing mental health of workers (Mental Health Action Check List: MHACL) was developed. The use of the checklist for primary prevention was examined. MHACL was developed through three steps: (1) Review of related references and collection of improvement examples for designing a draft MHACL; (2) pilot application of the draft at industrial workplaces and trials at workshops of occupational health staff; and (3) proposing a new MHACL for general use in industry. Workplace improvement actions related to mental health were listed in eight technical areas. From 84 workplaces in Japan, 201 such actions were collected. Typical improvement action phrases were extracted based on these examples, and a draft MHACL containing 40 generally applicable actions were prepared. This draft was applied to selected workplaces for its use as a tool for group discussion. Then, the utility of the checklist was discussed by 105 occupational health staff working in public service offices. The workshop suggested modifications of the draft MHACL including improved check items and usage procedures and the need to use easy-to-understand actions. The final version of the MHACL comprised 30 items in six technical areas: A) sharing work planning, B) work time and organization, C) ergonomic work methods, D) workplace environment, E) mutual support in the workplace, and F) preparedness and care. A new action checklist was proposed for use as a means of changing existing workplace environments and proposing practical actions for improving it. The checklist was confirmed to be useful for organizing workplace-level discussion for identifying immediate improvements at the workplace. The checklist is expected to be widely applied for promoting primary prevention measures in terms of better mental health. PMID- 17721061 TI - Recent progress in sensory mechanism. AB - Pain serves as a warning of impending injury, triggering appropriate protective responses. Emotional and cognitive processing in the brain is involved in the sensation of pain. As Ca(2+) waves in keratinocytes are mediated by the release of extracellular molecules such as signaling molecules, this may also affect the activity of surrounding cells such as sensory neurons. Although no junctions have been found between keratinocytes and sensory termini, ultrastructural studies have shown that keratinocytes come into contact with dorsal root ganglion neurons through membrane-membrane apposition. There is also indirect evidence that keratinocytes communicate with sensory neurons via extracellular molecules. Sensory neurons themselves sense various external stimuli, but there may also be skin-derived regulatory mechanisms by which sensory signaling is modulated.First, we will give a general outline of the subject: 1) Progress in identifying cortical loci that process pain messages is needed. 2) Far greater advances have been made in understanding the molecular mechanisms whereby primary sensory neurons detect pain-producing stimuli. 3) Genetic studies have facilitated the identification and functional characterization of molecules. 4) Now, the relationship between sensory and ion channels has become clear. PMID- 17721062 TI - Effects of sex hormones on rat tongue carcinoma induced by 4-nitroquinoline 1 oxide (4NQO). AB - We investigated the regulatory effects of sex hormones on tongue carcinoma initiated by orally administration 4-nitroquinoline 1-oxide (4NQO) to rats. Animals of either sex were classified into three groups. The male rats in each group received an estrogen administration (Me), orchiectomy (Mor), or both treatments (Me/or) while the female rats also received testosterone administration (Ft), ovariectomy (Fov), or both treatments (Ft/ov). The differences in the carcinogenic progress among these groups were examined by macroscopic and microscopic observation of tongue tissues. The incidence of cancer in the tongue tissue was 100% in the group reinforced with testosterone (testosterone+group) (Ft, Ft/ov, Me) but only 56.0% in the group not reinforced with testosterone (testosterone-group) (Fov, Mor). These findings suggest that sex hormones play a role in the onset of 4NQO-induced tongue carcinoma. PMID- 17721063 TI - Morphological study on quadruplets by cephalometric and model analyses. AB - Clarifying the genetic factors involved in maxillofacial growth and development is very important in orthodontic treatment planning and prognosis. However, few dental studies have examined multiple births. The present orthodontic evaluation was conducted using orthodontic data from a set of quadruplets. Orthodontic evaluation was performed on a set of quadruplets (1 girl and 3 boys) aged 9 years and 7 months at the initial visit. Although all 4 children weighed only about 1,400 g each at birth, height and body weight subsequently normalized. Mean skeletal age of the quadruplets was 10 years and 2 months, about 6 months ahead of their calendar age. In all 4 children, facial profile was mostly symmetrical and convex. Intraoral findings showed a Hellman's dental age of IIIA, together with spacing of the upper anterior teeth. Both overbite and overjet were 5-7 mm, and mesial step of the terminal plane was noted. Model analysis showed that tooth materials were on the large side, while arch width was narrow. Cephalometric analysis revealed that the ANB of the first- and fourth-born children was 6 degrees , and skeletal maxillary protrusion due to mandibular retrusion was diagnosed. The second- and thirdborn children exhibited no marked skeletal abnormalities. PMID- 17721064 TI - Pre-operative drilling simulation method for dental implant treatment. AB - The position, depth and direction of implant placement are often planned based on evaluation of radiographs and study casts. Insertion planned in such a manner may not be adequate for precise and safe surgery in some cases due to inadequate working clearance in the oral cavity. In order to obtain high initial stability and ensure osseointegration at the implant-bone interface, careful and precise drilling must be performed at the implant placement site. Therefore, we propose the necessity of evaluating the operability of implant treatment-devices prior to surgery. The amount of handling space needed during implant placement surgery was determined. The results showed that for implants with a length of 7-18 mm, a vertical distance of as much as 50-60 mm was required, depending on the implant platform. These results suggest the necessity of pre-operative drilling simulation in each individual. Handling space was measured with angled heads and probes fabricated on a trial basis for pre-surgical drilling simulation in the oral cavity. We believe that these instruments may be clinically useful in estimating the amount of handling space required prior to surgery and ensuring precise implant placement. Evaluation of the intra-oral environment for handling of treatment devices should be included in the pre-surgical intra-oral evaluation of dental implant cases to avoid changes in treatment planning due to intra-oral interference during the course of surgery. PMID- 17721065 TI - Epinephrine in local anesthetic cancels increase in tongue mucosal blood flow after stellate ganglion block in rabbit. AB - The goal of this study was to compare oral mucosal blood flow and duration of anesthetic action after stellate ganglion block (SGB) using lidocaine, with or without epinephrine, and discuss the effect of epinephrine on SGB. Duration of anesthetic action was defined as elapsed time from finish of injection to recovery of common carotid blood flow (CCBF) to within+/-5% of respective control value. Male Japan White rabbits were anesthetized with isoflurane and mechanically ventilated. Common carotid blood flow and tongue mucosal tissue blood flow (TMBF) were measured with an ultrasound flowmeter and laser Doppler flowmeter, respectively. End-tidal partial pressure of carbon dioxide (ETCO(2)) and hemodynamic variables were continuously monitored, including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP). For SGB, the tip of the needle was placed on the left transverse process of the cervical vertebra, 1-2 mm caudal to the cricoid cartilage. Either 0.1 ml of 1% lidocaine (Group L) or 1% lidocaine containing 10 mug/ml epinephrine (Group LE) was injected for SGB. There were no differences in values at immediately before SGB and at the time when maximal change in CCBF was observed after SGB for ETCO(2), HR, SBP, DBP or MAP in either group. CCBF showed a significant increase in Group L after SGB. In contrast, CCBF only showed a slight increase in Group LE. TMBF showed a significant increase in Group L after SGB, but not in Group LE. No differences in time required for maximal effect were observed between the two groups. In contrast, duration of anesthetic action in Group LE was significantly longer than that in Group L. Addition of epinephrine to local anesthetic solutions is not suitable for SGB, as it may not facilitate an increase in tissue blood flow, which is the primary objective of SGB. PMID- 17721066 TI - 2006 update on genetic determinants of osteoporosis. AB - Since the identification of vitamin D gene, the first one characterised by being related to osteoporosis, a high number of genetic studies, especially association studies, emerged to elucidate the genetic complex pattern of this disease. Osteoporosis is a skeletal chronic multifactorial disease, characterised by abnormal low bone mass and microarchitectural deterioration of bone tissue. It is getting a more and more important health problem, affecting a larger number of people, especially in developed countries. Studies demonstrated that variations in several genes, involved in bone metabolism, lead to the osteoporotic condition. Understanding the pathogenesis of osteoporosis requires the genetic characterization of the relationship among multiple gene variants, the encoded proteins, and the environmental mediators vs bone physiology. This paper pretends to give a panoramic on actual genetics of osteoporosis situation, taking into account the most important recent genetic studies in the field. PMID- 17721067 TI - Role of the cholesterol biosynthetic pathway in osteoblastic differentiation. AB - Cholesterol (C27H46O) is the principal structural lipid of the biological membrane, but it also plays an important role in many other biological functions. Even though the majority of body cholesterol is synthesized by the liver and secreted as circulating lipoproteins, many cell types can synthesize cholesterol ex novo. The biosynthetic pathway of cholesterol proceeds through several intermediates and involves different enzymes. The rate-limiting step of cholesterol synthesis is the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase that synthesizes mevalonate starting from HMG-CoA. Since natural inhibitors of HMG-CoA reductase, named statin, have been isolated, many others have been developed, which differ in their lipophilicity/ hydrophilicity. By using statins, many studies have been performed in order to shed light on the role of cholesterol on different cell types and, among these, on bone cells. In vivo studies have demonstrated that treatment of pluripotent mouse marrow stromal cells (M2-10B4) with statins inhibited the differentiation of these cells into osteoblastic cells, confirming the crucial role of cholesterol biosynthetic pathway for osteoblast differentiation. Conversely, other studies, using other cellular systems, have reported that statins may exert an anabolic effect on bone. Moreover, human and animal studies have shown that hypercholesterolemia may play an adverse effect in osteoporotic bone loss. In conclusion, it appears that cholesterol is important for different cellular activities, such as osteoblastic differentiation, if present in "normal" physiological concentration and particular experimental conditions, but it may exert adverse effects if present in excess. PMID- 17721068 TI - Role of biochemical markers of bone remodeling in clinical practice. AB - Bone tissue is subject to remodeling throughout the lifetime of an individual. Through a continuous remodeling cycle, actuated via the so-called 'bone remodeling units', old bone is resorbed by osteoclasts with the formation of cavities that are subsequently filled by osteoblasts. Bone loss observed in old age and in women after menopause is due to an imbalance between bone resorption and formation. Biochemical markers provide a dynamic view of the remodeling process, which covers rate of turnover and pathogenesis, and should improve fracture risk prediction. Furthermore, they can be used to monitor the short-term effects of therapy, and indicate if an excessive slowing of the remodeling process is occurring. When searching for markers of bone remodeling, biochemists have focused mainly on skeletal molecules that can be dosed in plasma and/or urine, as indicators of osteoblast function (i.e. bone alkaline phosphatase, osteocalcin, procollagene I C- and N-terminal propeptides) or osteoclast function (i.e. pyridinium crosslinks, collagen I C- and N-terminal telopeptides). The clinical significance of any marker for bone remodeling depends on two fundamental characteristics: specificity and variability. If the objective is to monitor therapeutic efficacy, it seems most rational to use a resorption marker for drugs that act principally on osteoclast, such as estrogens or bisphosphonates, while for drugs that act principally on osteoblast, such as PTH peptides a marker for bone formation would be more appropriate. PMID- 17721069 TI - Bone metabolism in men: role of aromatase activity. AB - Sex steroid hormones play an important role in the maintenance of bone mass in males and in females. Even though androgens are the major sex steroids in men, direct and indirect evidence emerged suggesting that estrogens may also play a major role in male skeletal health. Since the testes account for only 15% of circulating estrogens in males, the remaining 85% comes from peripheral aromatization of androgen precursors in different tissues, including bone. Human models of aromatase deficiency clearly demonstrated the critical importance of the conversion of androgens into estrogens in regulating male skeletal homeostasis. Aromatase- deficient men showed tall stature due to continued longitudinal growth, unfused epiphyses, high bone turnover, and osteopenia. Interventional studies in adult men using aromatase inhibition confirmed that estrogens are important in controlling bone remodeling. Importantly either inherited (i.e. due to common polymorphisms at the human aromatase CYP19 gene) or acquired (i.e. by diseases or different compounds) variation in aromatase ability to convert androgen precursors into estrogen may also be relevant for skeletal homeostasis. PMID- 17721070 TI - Role of vitamin K on biochemical markers, bone mineral density, and fracture risk. AB - Osteoporosis is a multifactorial chronic disease that may become even more prevalent and more of a public health problem in the decades to come. Recent research has indicated that a number of macro- and micronutrients are involved in the development of bone health. In the past decade it became evident that vitamin K played a significant role in human health beyond its well-established function in blood clotting. In fact, among the proteins known or suspected to be involved in bone and vascular biology there are several members of the vitamin K dependent or gamma-carboxyglutamic acid protein family. Based on the current evidence from epidemiologic and intervention studies, there are insufficient data to recommend a routine supplementation of vitamin K for optimal bone health. New experimental and placebo-controlled studies in humans should clarify our understanding of the role vitamin K plays in improving bone health. PMID- 17721071 TI - Hyperphosphatemia: effects on bone metabolism and cardiovascular risk. AB - Hyperphosphatemia indicates a plasma inorganic phosphate (Pi) concentration greater than 5 mg/dl in the adult and 7 mg/dl in adolescent subjects. Pi homeostasis is maintained by several mechanisms (intestinal absorption, renal excretion, balance of Pi exchanges in and out of the cells, hormonal regulation). Most of the Pi, after intestinal absorption, undergoes urinary excretion suggesting that the kidney plays a major role in the maintenance of homeostasis and plasma concentration of the Pi, modifying its reabsorption in the proximal tubule where 3 types of sodium/ phosphate cotransporters have been identified (NPT). NPT2 is crucial for the Pi reabsorption and is modulated by several hormones (PTH and vitamin D3, phosphatonins) and non-hormonal factors. The hyperphospatemia is usually due to a decrease in renal function or a PTH absence (primary or secondary hypoparathyroidism) or phosphatonin deficiency. A correct serum Pi concentration is a critical condition for maintaining the calcium phosphate (CaxPi) product within a safe range ensuring the physiological processes of bone mineralization; an increase of CaxPi product in extracellular fluids over a critical threshold, may promote processes of extraskeletal calcification. In the last few years several studies have shown that the pathogenetic mechanisms of vascular calcification do not imply a simple deposition of calcium phosphate crystals in the wall of the vessels affected by atherosclerotic lesions, but an active process making vascular smooth cells assume functional characteristics of osteoblasts. The consequences on bone are heterogeneous according to the pathogenetic mechanisms responsible for hyperphosphatemia. PMID- 17721073 TI - Osteoporosis and body composition. AB - The Epidemiologic Study on the Prevalence of Osteoporosis in Italy showed that the prevalence of osteoporosis among women and men aged 60 yr and over is 22.8% and 14.5%, respectively, giving rise to about 80,000 new fractures a yr. Sarcopenia is considered to be one of the main features of the aging process. It is characterized by a reduction in muscle mass and muscle strength, and affects women more than men. It is associated with a increased risk of fractures consequent upon a greater predisposition to falls, but also to the lack of bone remodeling due to reduced muscle mechanical strength. Muscle strength determines quality bone modifications such as density, strength, and microarchitecture. Variations in the ratios of cortical and muscle areas give rise to various types of osteoporosis, with different risks of fracture. Bone mineral density increases with body fat mass, and obesity has a protective effect against osteoporosis. This protective effect is explained by a combination of hormonal (peripheral aromatization of androgens to estrogens in adipose tissue) and mechanical factors (on weight-bearing bone sites), but the hormone leptin also probably mediates fat and bone mass. Serum leptin levels are closely related to body fat mass, and some findings suggest the peripheral effect of leptin, which exerts estrogenic effects, enhancing osteoblastic differentiation and inhibiting late adipocytic differentiation. The overall effect of leptin on bone results from a balance between negative central effects and positive direct peripheral effects, according to serum leptin levels. PMID- 17721072 TI - The role for growth hormone in linking arthritis, osteoporosis, and body composition. AB - Adults with either GH deficiency (GHD) or GH excess have bone, metabolic, and somatic impairments. This review deals with available data on the relationship between GH status, bone mass, articular disorders, and body composition. GHD subjects have reduced bone mineralization and increased fracture rates. Acromegalic artropathy occurs in virtually all patients and in its late degenerative stages may resemble osteoarthritis. Abnormalities in GH/IGF-I were observed in patients with different forms of arthritis. When concerning body composition (BC), both severe and partial GHD are characterized by increased fat mass, especially truncal, and reduced lean mass. In acromegaly, an increase in body weight, lean mass, and extracellular water, and reduced fat mass were observed; these abnormalities did not always disappear after the normalization of GH/IGF-I levels. On the contrary, long-term GH replacement at physiological doses improved the abnormalities in BC and increased bone mineral density in men with adult-onset GHD, but discordant data were obtained for the bone effects in women. In conclusion, both GHD and GH excess are responsible for some well-defined alterations in metabolism, BC, bone mass, and joint physiology. Their normalization (by GH replacement or treatment of acromegaly) reverses most of these abnormalities, thus confirming their GH-related etiology. PMID- 17721074 TI - Protein intake: the impact on calcium and bone homeostasis. AB - Bone density depends on various factors such as age, hormonal status, genetics factors and lifestyle: a balanced diet plays a fundamental role in the prevention of osteoporosis. The role of protein intake on bone health is still controversial: this review is focused on the relation between protein intake and bone metabolism. PMID- 17721075 TI - Metabolic bone diseases during long-term total parenteral nutrition. AB - Long-term total parenteral nutrition (TPN) is a procedure commonly applied to patients with advanced forms of intestinal malabsorption. Among TPN complications, bone metabolic diseases, such as osteoporosis and osteomalacia, are a common finding. Initially considered to be a manifestation of aluminium toxicity which followed massive contamination with the element of the solutions used in TPN, metabolic osteopathy during TPN is currently considered a multiform syndrome, with a multifactorial pathogenesis, which may manifest itself with vague or clear clinical pictures. In this review, we analyse clinical, pathogenetic, and therapeutic aspects of the most common bone metabolic diseases in patients undergoing long-term TPN. PMID- 17721076 TI - Targeting the p53 family for cancer therapy: 'big brother' joins the fight. AB - Inactivation of p53-mediated signaling plays a major role in both the genesis and therapy resistance of human cancer. Nearly all tumors contain mutations in p53 itself or have perturbations in the p53 pathway. Since there is clear evidence that many tumor cells are more likely to die in response to wild-type p53 activation or restoration than are their normal counterparts, there has been considerable interest in the development of small molecules that target p53 for therapeutic gain. These include compounds that either revert mutant p53 back to its wild-type conformation or compounds which interfere with the binding to, or the ubiquitylation of, p53 by MDM2. In both cases, however, the efficacy of the strategy depends on the presence of either mutant or wild-type p53 respectively thereby limiting their application to specific tumor settings. As a result, recent strategies have turned to the p53 family member, p73, which like p53 is a potent inducer of death, but in contrast is rarely lost or mutated in tumors. We discuss here all these different strategies and in particular focus on the discovery of an apoptotic peptide which targets not just p73, but potentially all p53 family members to cause tumor cell death. PMID- 17721077 TI - Regulation of p27Kip1 by miRNA 221/222 in glioblastoma. AB - Levels of p27(Kip1), a key negative regulator of the cell cycle, are often decreased in cancer. In most cancers, levels of p27(Kip1) mRNA are unchanged and increased proteolysis of the p27(Kip1) protein is thought to be the primary mechanism for its downregulation. Here we show that p27(Kip1) protein levels are also downregulated by microRNAs in cancer cells. We used RNA interference to reduce Dicer levels in human glioblastoma cell lines and found that this caused an increase in p27(Kip1) levels and a decrease in cell proliferation. When the coding sequence for the 3'UTR of the p27(Kip1) mRNA was inserted downstream of a luciferase reporter gene, Dicer depletion also enhanced expression of the reporter gene product. The microRNA target site software TargetScan predicts that the 3'UTR of p27(Kip1) mRNA contains multiple sites for microRNAs. These include two sites for microRNA 221 and 222, which have been shown to be upregulated in glioblastoma relative to adjacent normal brain tissue. The genes for microRNA 221 and microRNA 222 occupy adjacent sites on the X chromosome; their expression appears to be coregulated and they also appear to have the same target specificity. Antagonism of either microRNA 221 or 222 in glioblastoma cells also caused an increase in p27(Kip1) levels and enhanced expression of the luciferase reporter gene fused to the p27(Kip1) 3'UTR. These data show that p27(Kip1) is a direct target for microRNAs 221 and 222, and suggest a role for these microRNAs in promoting the aggressive growth of human glioblastoma. PMID- 17721078 TI - The Par-1/MARK family of protein kinases: from polarity to metabolism. AB - The Par-1 protein kinases are conserved from yeast to man and belong to a subfamily of kinases that includes the energy sensor and metabolic regulator, AMPK. Par-1 is regulated by LKB1 and atypical PKC and has been shown in multiple organisms and cell types to be critical for regulation of cellular polarity. Recent studies using knockout mice have revealed several surprising physiological functions for Par-1b/MARK2/EMK1. Our recent study shows that Par-1b regulates metabolic rate, adiposity and insulin sensitivity. This is the first study to implicate these kinases in metabolic functions akin to those previously defined for AMPK. Conversely, another series of recent publications now implicate AMPK in regulation of polarity. Here we discuss the metabolic phenotype seen in Par-1b deficient mice and the synthesis of several findings that link Par-1 and AMPK to a degree that has not been previously appreciated. PMID- 17721080 TI - Non-catalytic function for ATR in the checkpoint response. AB - The ATR family of checkpoint kinases is essential for an appropriate response to genomic insults in eukaryotes. Included in this family are Mei-41 in Drosophila, Mec1 inS. cerevisiae, Rad3 in S. pombe, and ATR in vertebrates. These large kinases phosphorylateand modify multiple cell cycle and checkpoint factors, leading to cell cycle arrest, DNA repair, and induction of apoptosis. The catalytic domain of all ATR family members comprises only a fraction of the total protein. Here, we show that the non-catalytic portion of ATR has a conserved function in the checkpoint response. Expression of either wild type or various kinase defective forms of Xenopus ATR (XATR) in S. cerevisiae mec1 mutants suppresses the checkpoint defect and induces a DNA damage dependent mitotic cell cycle arrest. This suppression requires the presence of yeast Ddc2 and Rad9 but functions independently of Rad9 modification and Rad53 activation. Our results indicate that XATR is not functioning through the established mitotic checkpoint pathways. Instead, we find that the XATR suppression of the mec1 mutant checkpoint defect requires the spindle checkpoint factors Mad1 and Mad2, suggesting a role for XATR in the spindle assembly checkpoint. Finally, we show that a yeast strain expressing a truncated, kinase domain deleted form of mec1 from the endogenous locus is partially checkpoint proficient and induces a mitotic cell cycle arrest in a Mad2 dependent manner. Thus, the link between the non-catalytic region of the ATR kinase family and the spindle checkpoint pathway is conserved. PMID- 17721079 TI - Cell cycle- and ribonucleotide reductase-driven changes in mtDNA copy number influence mtDNA Inheritance without compromising mitochondrial gene expression. AB - Most eukaryotes maintain multiple copies of mtDNA, ranging from 20-50 in yeast to as many as 10,000 in mammalian cells. The mitochondrial genome encodes essential subunits of the respiratory chain, but the number of mtDNA molecules is apparently in excess of that needed to sustain adequate respiration, as evidenced by the "threshold effect" in mitochondrial diseases. Thus, other selective pressures apparently have contributed to the universal maintenance of multiple mtDNA molecules/cell. Here we analyzed the interplay between the two pathways proposed to regulate mtDNA copy number in Saccharomyces cerevisiae, and the requirement of normal mtDNA copy number for mitochondrial gene expression, respiration, and inheritance. We provide the first direct evidence that upregulation of mtDNA can be achieved by increasing ribonucleotide reductase (RNR) activity via derepression of nuclear RNR gene transcription or elimination of allosteric-feedback regulation. Analysis of rad53 mutant strains also revealed upregulation of mtDNA copy number independent of that resulting from elevated RNR activity. We present evidence that a prolonged cell cycle allows accumulation of mtDNA in these strains. Analysis of multiple strains with increased or decreased mtDNA revealed that mechanisms are in place to prevent significant changes in mitochondrial gene expression and respiration in the face of approximately two fold alterations in mtDNA copy number. However, depletion of mtDNA in abf2 null strains leads to defective mtDNA inheritance that is partially rescued by replenishing mtDNA via overexpression of RNR1. These results indicate that one role for multiple mtDNA copies is to ensure optimal inheritance of mtDNA during cell division. PMID- 17721081 TI - Mitotic bypass via an occult cell cycle phase following DNA topoisomerase II inhibition in p53 functional human tumor cells. AB - Cells cycle checkpoints guard against the inapproriate commitment to critical cell events such as mitosis. The bisdioxxopiperazzine ICRF-193, a catalytic inhibitor of DNA topoisomerase II causes a reversible stalling of the exit of cells from G(2) at the decatenation checkpoint (DC) and can generate tetraploidy via the compromising of chromosome segregation and mitotic failure. We have addressed an alternative origin-endocycle entry-for the tetraploidisation step in ICRF-193 exposed cells. Here we show that DC-proficient p53-functional tumor cells can undergo a transition to tetraploidy and subbsequent aneuploidy via an initial bypass of mitosis and the mitotic spindle checkpoint. DC-deficient SV4 tranformed cells move exclusively through mitosis to tetraploidy. In p53 functional tumor cells, escape through mitosis is enhanced by dominant negative p53 co-expression. The mitotic bypass transition phase (termed G(2)(endo)) disconnects cyclin B1 degradation from nuclear envelope breakdown and allows cells to evade the action of Taxol. G(2)(endo) constitutes a novel and alternative cell cycle phase-lasting some 8 h-with distinct molecular motifs at its boundaries for G(2) exit and subsequent entry into a delayed G(1) tetraploid state. The result challenge the paradigm that checkpoint breaching leads directly to abnormal ploidy states via mitosis alone. We further propose that the induction of bypass could: facilitate the covert development of tetraploidy in p53 functional cancers, lead to a misinterpretation of phase allocation during cell cycle arrest and contribbute to tumor cell drug resistance. PMID- 17721082 TI - Towards a better way to die with chemotherapy: role of heat shock protein exposure on dying tumor cells. AB - The ultimate goal of most anti-tumor therapies is to kill tumor cells. While most of the attention in cancer therapy has been towards enhancing the death of tumor cells, the effect of dying tumors on the immune system has been less studied. Recent studies have suggested that cell death induced by different agents may have distinct consequences for the immune system. One of the immunogenic signals may be the expression of heat shock proteins on dying tumor cells under certain settings. For example, bortezomib(a proteasome inhibitor) induces the expression of heat shock protein 90 (hsp90) on the surface of dying human myeloma tumor cells. Recognition of such tumor cells by antigen presenting dendritic cells leads to the generation of anti-tumor T cells. Harnessing the properties of some anti-tumor agents to induce immunogenic death of tumor cells may facilitate the recruitment of adaptive immunity and promote the durability of anti-tumor effects. PMID- 17721083 TI - Initiation of high frequency multi-drug resistance following kinase targeting by siRNAs. AB - The sequential use of non cross-resistant cytotoxic agents is the standard of care for advanced solid tumors in order to enhance survival and optimise quality of life. Nevertheless, drug resistance to non cross-resistant agents is commonly witnessed, with clinical response rates to non cross-resistant regimens declining as the disease advances. Expression of ABC transporters is unlikely to fully explain this phenomenon, and a clear molecular explanation for this process remains uncertain. A statistical analysis of a recently published RNA interference screen targeting 779 kinases in three cell lines deriving from different tumor types reveals a significant correlation between resistance to paclitaxel and a non cross-resistant cytotoxic agent. Furthermore, 20% of kinases that promote resistance to paclitaxel when targeted by RNAi also promote resistance to a non cross-resistant agent within that same cell line, consistent with a tissue-type dependence of multi-drug resistance. Conversely, paclitaxel specific resistance and sensitising kinases occur less frequently than expected. This indicates that several cell line specific kinases may regulate multi-drug resistance and provide a potential explanation for the phenomenon of drug resistance to non cross-resistant agents witnessed in oncology practice. Furthermore, this work supports efforts to identify common pathways of drug response for future drug discovery programmes. PMID- 17721085 TI - E6/E7 of HPV type 16 promotes cell invasion and metastasis of human breast cancer cells. AB - Human papillomaviruses (HPVs) could be important risk factors for breast carcinogenesis and metastasis, as roughly 50% of breast cancers are positive for high-risk HPVs. To determine the role of high-risk HPVs in human breast carcinogenesis and metastasis, we examined the effect of E6/E7 of HPV type 16 in two non-invasive breast cancer cell lines, MCF7 and BT20. We report that E6/E7 of HPV type 16 induces cell invasive and metastatic abilities of MCF7 and BT20 in vitro and in vivo, respectively, in comparison with the wild type cells. This is accompanied by an upregulation of Id-1, a family member of helix-loop-helix (HLH) transcription factors, in MCF7 and BT20 cell lines which express E6/E7. Earlier studies have reported that Id-1 regulates cell invasion and metastasis of human breast cancer cells. To gauge the role of Id-1 in cell invasion and metastasis induced by E6/E7 of HPV type 16, we investigated the effect of E6/E7 in mouse normal embryonic fibroblast (NEF) and knockout Id-1 (Id-1(-/-)) cells. We establish that E6/E7 induces cell invasive ability in NEF but not Id-1(-/-) cells; moreover, we were able to inhibit the invasion ability of MCF7-E6/E7 and BT20-E6/E7 using Id-1 antisense retroviruses. Furthermore, we report that E6/E7 oncoproteins up-regulate Id-1 promoter activity in MCF7 and BT20 cells. We also found that HPV type 16 is present in all invasive and metastatic breast cancer and less frequently in in-situ breast cancer as opposed to normal mammary tissue. In parallel, we demonstrate that Id-1 overexpression is correlated with the presence of HPV type 16 in human invasive and metastatic breast cancer. These data suggest that high-risk HPV infections can induce cell invasion and metastasis in breast cancer through Id-1 regulation. PMID- 17721084 TI - Galpha13 regulation of proto-Dbl signaling. AB - Rho family GTPases play important roles in the regulation of intracellular signals induced by activated heterotrimeric G proteins of the alpha(12/13) family. The alpha(12/13) subunits activate Rho GTPases through direct binding to a group of Rho guanine nucleotide exchange factors (GEFs) characterized by the presence of a G protein signaling-like (RGL) domain. The Rho GEF proto-Dbl, that does not contain a RGL domain, was also found to link Galpha(12/13) signals to Rho. We have explored the effects of activated Galpha(13) and Galpha(13) associated G protein-coupled receptor (GPCR) agonists on proto-Dbl regulation. We show that activated Galpha(13), but not Galpha(12) or Galpha(q), induces translocation of proto-Dbl to the cell membrane with consequent enlargement of cell body and membrane ruffling. These effects were evident also when Galpha(13) associated GPCR agonists were used on cells expressing proto-Dbl and were accompanied by the activation of Cdc42 and RhoA GTPases and further downstream effector JNK and p38 kinases. Moreover, we show that both activated Galpha(13) and GPCR agonists stimulate proto-Dbl interaction with ezrin to promote ezrin translocation to the plasma membrane. These results suggest a mechanism by which proto-Dbl and its effector pathways are regulated by Galpha(13)-mediated signals through association with ezrin. PMID- 17721086 TI - Tuning cell cycle regulation with an iron key. AB - Iron (Fe) is essential for cellular metabolism e.g., DNA synthesis and its depletion causes G(1)/S arrest and apoptosis. Considering this, Fe chelators have been shown to be effective anti-proliferative agents. In order to understand the anti-tumor activity of Fe chelators, the mechanisms responsible for G(1)/S arrest and apoptosis after Fe-depletion have been investigated. These studies reveal a multitude of cell cycle control molecules are regulated by Fe. These include p53, p27(Kip1), cyclin D1 and cyclin-dependent kinase 2(cdk2). Additionally, Fe depletion up-regulates the mRNA levels of the cdk inhibitor, p21(CIP1/WAF1), but paradoxically down-regulates its protein expression. This effect could contribute to the apoptosis observed after Fe-depletion. Iron-depletion also leads to proteasomal degradation of p21(CIP1/WAF1) and cyclin D1 via an ubiquitin independent pathway. This is in contrast to the mechanism in Fe-replete cells, where it occurs by ubiquitin-dependent proteasomal degradation. Up-regulation of p38 mitogen-activated protein kinase (MAPK) after Fe-depletion suggests another facet of cell cycle regulation responsible for inhibition of proliferation and apoptosis induction. Elucidation of the complex effects of Fe-depletion on the expression of cell cycle control molecules remains at its infancy. However, these processes are important to dissect for complete understanding of Fe-deficiency and the development of chelators for cancer treatment. PMID- 17721087 TI - Endogenous K-ras signaling in erythroid differentiation. AB - K-ras is one of the most frequently mutated genes in virtually all types of human cancers. Using mouse fetal liver erythroid progenitors as a model system, we studied the role of endogenous K-ras signaling in erythroid differentiation. When oncogenic K-ras is expressed from its endogenous promoter, it hyperactivates cytokine-dependent signaling pathways and results in a partial block in erythroid differentiation. In erythroid progenitors deficient in K-ras, cytokine-dependent Akt activation is greatly reduced, leading to delays in erythroid differentiation. Thus, both loss- and gain-of-Kras functions affect erythroid differentiation through modulation of cytokine signaling. These results support the notion that in human cancer patients oncogenic Ras signaling might be controlled by antagonizing essential cytokines. PMID- 17721088 TI - Current V3 genotyping algorithms are inadequate for predicting X4 co-receptor usage in clinical isolates. AB - OBJECTIVE: Integrating CCR5 antagonists into clinical practice would benefit from accurate assays of co-receptor usage (CCR5 versus CXCR4) with fast turnaround and low cost. DESIGN: Published HIV V3-loop based predictors of co-receptor usage were compared with actual phenotypic tropism results in a large cohort of antiretroviral naive individuals to determine accuracy on clinical samples and identify areas for improvement. METHODS: Aligned HIV envelope V3 loop sequences (n = 977), derived by bulk sequencing were analyzed by six methods: the 11/25 rule; a neural network (NN), two support vector machines, and two subtype-B position specific scoring matrices (PSSM). Co-receptor phenotype results (Trofile Co-receptor Phenotype Assay; Monogram Biosciences) were stratified by CXCR4 relative light unit (RLU) readout and CD4 cell count. RESULTS: Co-receptor phenotype was available for 920 clinical samples with V3 genotypes having fewer than seven amino acid mixtures (n = 769 R5; n = 151 X4-capable). Sensitivity and specificity for predicting X4 capacity were evaluated for the 11/25 rule (30% sensitivity/93% specificity), NN (44%/88%), PSSM(sinsi) (34%/96%), PSSM(x4r5) (24%/97%), SVMgenomiac (22%/90%) and SVMgeno2pheno (50%/89%). Quantitative increases in sensitivity could be obtained by optimizing the cut-off for methods with continuous output (PSSM methods), and/or integrating clinical data (CD4%). Sensitivity was directly proportional to strength of X4 signal in the phenotype assay (P < 0.05). CONCLUSIONS: Current default implementations of co-receptor prediction algorithms are inadequate for predicting HIV X4 co-receptor usage in clinical samples, particularly those X4 phenotypes with low CXCR4 RLU signals. Significant improvements can be made to genotypic predictors, including training on clinical samples, using additional data to improve predictions and optimizing cutoffs and increasing genotype sensitivity. PMID- 17721090 TI - HIV, infant feeding, and survival: old wine in new bottles, but brimming with promise. PMID- 17721089 TI - Executive summary and recommendations from WHO/UNAIDS and AAVP consultation on: 'The inclusion of adolescents in HIV vaccine trials', 16-18 March 2006 in Gaborone, Botswana. AB - This report summarizes the discussions and recommendations from a consultation held in Gaborone, Botswana (16-19 March 2006), organized by the joint World Health Organization (WHO)/United Nations Programme on HIV/AIDS (UNAIDS) HIV Vaccine Initiative (HVI) and the African AIDS Vaccine Programme (AAVP). The consultation considered key challenges and strategies in enrolling adolescents into HIV vaccine clinical trials, relevant to developing countries, in particular in eastern and southern Africa. Approaches were identified that might address and resolve country-specific challenges related to scientific, legal, ethical, regulatory and community aspects of the involvement of adolescents in HIV vaccine trials. This executive summary is formulated for a broader dissemination of the outcomes of the meeting to the general clinical, scientific and regulatory community involved in the review, approval and monitoring of clinical trials and potential licensing of HIV vaccine candidates. Four major topics were discussed and recommendations developed with regard to: (i) criteria for products selection and clinical trial design; (ii) ethical and legal issues; (iii) community acceptance and participation; and (iv) regulatory considerations. The recommendations of this meeting were further discussed and endorsed by the WHO/UNAIDS HIV Vaccine Advisory Committee. PMID- 17721091 TI - Efficacy of a multigenic protein vaccine containing multimeric HIV gp160 against heterologous SHIV clade C challenges. AB - OBJECTIVE: To determine whether multigenic protein immunogens including native, trimeric HIV clade C (HIV-C) gp160 could cross-protect macaques against mucosal challenge with clade C (SHIV-C) mismatched for env. DESIGN: Because AIDS vaccine recipients are unlikely to encounter exactly matched HIV strains and to represent the diversity of locally circulating HIV-C strains, we selected env genes to generate the gp160 immunogen and SHIV-C from different, recently infected infants of the same clinical cohort in Zambia. In a model of postnatal HIV-C transmission, infant macaques were immunized with soluble viral proteins, including trimeric HIV1084i Env, and challenged with SHIV-1157ip; protein-only vaccination was compared with a DNA prime/protein boost strategy. METHODS: All vaccinated and control monkeys were exposed orally to low-dose, R5-tropic SHIV 1157ip encoding heterologous env. Animals with no or only transient infection were rechallenged intrarectally with a high dose of R5 SHIV-1157ipd3N4, a 'late', animal-evolved SHIV-1157ip variant. Animals were followed prospectively for immune parameters and viral RNA loads. RESULTS: Vaccination induced cross neutralizing antibodies. Compared to controls, vaccinees had significantly lower peak viral RNA loads, and one vaccine recipient remained completely virus-free, even in lymphoid tissues. There was a trend for the protein-only vaccine to yield better protection than the combined modality approach. CONCLUSION: Protein-only immunogens induced significant protection against heterologous viruses encoding env from locally circulating viruses. PMID- 17721093 TI - Differential antiviral effect of PEG-interferon-alpha-2b on HIV and HCV in the treatment of HIV/HCV co-infected patients. AB - OBJECTIVE: The major antiviral effect of interferon (IFN)-alpha on hepatitis C virus (HCV) is blocking of virion production from infected cells. We now investigate the previously unknown mechanism of action of IFN-alpha against HIV. METHODS: HIV kinetics in parallel to HCV kinetics and IFN pharmacokinetics during pegylated-IFN-alpha-2b (1.5 microg/Kg q.w., PEG-IFN) and ribavirin (1-1.2 g daily) treatment in nine HIV patients co-infected with HCV genotype 1 were analyzed. In vivo modeling predictions of suppression of HIV replication by PEG IFN in CD8-depleted peripheral blood mononuclear cells were verified by in vitro experiments. RESULTS: HCV and HIV show different viral decline patterns after administration of PEG-IFN. Unlike the bi-phasic decline shown by HCV, HIV shows a slow continuous decline during the first week, with no rebound when PEG-IFN levels decline. Fitting of HIV kinetics with known half-lives of free virus and infected cells indicates that the major effect of IFN on HIV is to block de novo infection rather than to block virion production. The magnitude of the antiviral effect is similar (mean 1.1 log10 decline at 7 days) to those of direct anti-HIV drugs, but shows an inverse correlation with baseline viremia. In vitro studies show that preincubation with IFN renders a suppression of HIV replication superior to that of treatment postinfection, thus corroborating the mathematical analysis in vivo. CONCLUSION: The complimentary antiviral properties of IFN-alpha and antiretroviral therapy suggest a role for pharmacokinetically improved formulations of IFN as part of salvage therapy for HIV-infected individuals. PMID- 17721092 TI - Concentrations of zidovudine- and lamivudine-triphosphate according to cell type in HIV-seronegative adults. AB - INTRODUCTION: Concentrations of zidovudine (ZDV)- and lamivudine (3TC) triphosphates (TP) have been quantified in unfractionated peripheral blood mononuclear cells (PBMC) from HIV+ patients. The objective of this study was to determine whether concentrations of ZDV-TP and 3TC-TP in PBMC reflect the concentrations within CD4 T cells in HIV-seronegative adults. METHODS: Volunteers had taken 300 mg of ZDV plus 150 mg of 3TC twice daily for > or = 7 days. Blood (60 mL) was collected 2 or 5 h post observed dose. PBMC were processed into three cell fractions using CD4 magnetic immunobeads: CD4-purified cells; unfractionated PBMC; and CD4-depleted PBMC. TP were determined in each cell fraction with liquid chromatography-mass spectrometry and compared across cell types by non-parametric analyses. RESULTS: Six males and two females participated. The median (range) percentage of CD4 T cells (CD4%) in each fraction were: CD4-purified, 99%; unfractionated, 63% (range, 53-70); and CD4-depleted, 14% (range, 4-29). Corresponding median (range) ZDV-TP concentrations were 8.0 (5.3-10.3), 26.5 (12.9-42.2), and 34.2 (16.4-52.2) fmol/1 x 10 cells (Friedman P = 0.0008). The 3TC-TP values were 4.6 (2.3-6.7), 4.8 (3.5-8.8), and 6.8 (4.0-13.1) pmol//1 x 10 cells (Friedman P = 0.01). In mixed model analyses: ZDV-TP (fmol/1 x 10 cells) = 42-0.32 (CD4%); P < 0.001 and 3TC-TP (pmol/1 x 10 cells) = 7.3-0.03(CD4%); P = 0.003. CONCLUSIONS: In HIV-seronegative volunteers, 3TC-TP concentrations in PBMC reflected the concentrations within CD4 T cells, but ZDV-TP concentrations were more than 70% lower in CD4 T cells than in PBMC. Thus, TP concentrations differ according to cell type in vivo with corresponding efficacy and toxicity implications for cells with low or high triphosphates. PMID- 17721094 TI - Short-term clinical disease progression in HIV-1-positive patients taking combination antiretroviral therapy: the EuroSIDA risk-score. AB - OBJECTIVES: To derive and validate a clinically applicable prognostic score for predicting short-term disease progression in HIV-infected patients taking combination antiretroviral therapy (cART). DESIGN AND METHODS: Poisson regression was used to identify prognostic markers for new AIDS/death in patients taking cART. A score was derived for 4169 patients from EuroSIDA and validated on 5150 patients from the Swiss HIV Cohort Study (SHCS). RESULTS: In EuroSIDA, 658 events occurred during 22 321 person-years of follow-up: an incidence rate of 3.0/100 person-years of follow-up [95% confidence interval (CI), 2.7-3.3]. Current levels of viral load, CD4 cell count, CD4 cell slope, anaemia, and body mass index all independently predicted new AIDS/death, as did age, exposure group, a prior AIDS diagnosis, prior antiretroviral treatment and stopping all antiretroviral drugs. The EuroSIDA risk-score was divided into four strata; a patient in the lowest strata would have predicted chance of new AIDS/death of 1 in 801, 1 in 401 and 1 in 201 within the next 3, 6 or 12 months, respectively. The corresponding figures for the highest strata were 1 in 17, 1 in 9 and 1 in 5, respectively. A single unit increase in the risk-score was associated with a 2.70 times higher incidence of clinical progression (95% CI, 2.56-2.84) in EuroSIDA and 2.88 (95% CI, 2.75 3.02) in SHCS. CONCLUSIONS: A clinically relevant prognostic score was derived in EuroSIDA and validated within the SHCS, with good agreement. The EuroSIDA risk score will be made available publicly via an interface that will perform all calculations for the individual. PMID- 17721095 TI - Memantine and HIV-associated cognitive impairment: a neuropsychological and proton magnetic resonance spectroscopy study. AB - OBJECTIVE: To assess the safety and efficacy of memantine, an uncompetitive antagonist of the N-methyl-D-aspartate receptor as treatment of HIV-associated cognitive impairment. METHODS: This was a Phase II randomized, double-blind, placebo-controlled, multicenter trial within the Adult AIDS Clinical Trials Group. One-hundred and forty HIV-infected adults with mild to severe AIDS dementia complex receiving stable antiretroviral therapy were enrolled. Memantine was initiated at 10 mg daily escalated to 40 mg daily, or up to the maximum tolerated dose and continued for 16 weeks (primary evaluation visit) followed by a 4-week washout period and re-evaluation at week 20. Changes in cognitive performance were measured as percent change from baseline to week 16 in the average of eight neuropsychological test scores (NPZ-8). Brain metabolism was measured by magnetic resonance spectroscopy in a subgroup of subjects. RESULTS: Sixty-one percent of subjects in the memantine group and 85% in the placebo group reached the 40 mg dose while the reported adverse experiences between the two groups were similar. There were no significant improvements in neuropsychological performance over 16 weeks; however, memantine was associated with a significant increase at week 16 in the N-acetyl aspartate to creatine ratio, in the frontal white matter (P = 0.040) and parietal cortex (P = 0.023). CONCLUSIONS: Memantine was safe and tolerated by HIV-infected subjects with cognitive impairment. Although we observed no significant differences in cognitive performance, the magnetic resonance spectroscopy data suggest that memantine may ameliorate neuronal metabolism, an important step to stabilizing or preventing neuronal injury. These results underscore the need for longer studies to assess the full potential of neuroprotective agents. PMID- 17721096 TI - Long-term effects of intermittent interleukin-2 therapy in chronic HIV-infected patients (ANRS 048-079 Trials). AB - OBJECTIVE: Interleukin (IL)-2 therapy leads to significant CD4 cell increases in HIV-infected patients. Since phase III trials are ongoing, studies supporting the long-term feasibility of this strategy are needed. METHODS: We studied the long term outcomes of 131 patients treated with IL-2 in two studies initiated either before (ANRS 048) or following (ANRS 079) the advent of HAART. RESULTS: At the last assessment (median follow-up 3.4 years), these patients experienced a gain of 428 cells/microl and a decrease in plasma HIV RNA to 1.70 log10 copies/ml. In both studies, high CD4 cell counts were maintained with a median of ten 5-day cycles of subcutaneous IL-2. Median time since the last cycle was 2 years. At last assessment, 59% of 048 patients maintained a non-HAART regimen. Detailed analysis at week 170 showed that median CD4 cell counts were 856 (048) and 964 (079) cells/microl. This corresponded to a gain from baseline of 515 (048) and 627 (079) cells/microl. The median viral load decreases from baseline and corresponded to 1.70 (048) and 1.88 (079) log10 copies/ml. Comparisons across the studies showed that CD4 gains and viral load changes were similar whether HAART or non-HAART was used. The frequency of cycling, but not CD4 cell counts, viral loads or antiviral regimen at baseline, was predictive of long-term CD4 gain (P = 0.03). CONCLUSION: Altogether, these observations support IL-2 as a long-term therapeutic strategy in HIV infection. PMID- 17721097 TI - Antiretroviral drug exposure in the female genital tract: implications for oral pre- and post-exposure prophylaxis. AB - OBJECTIVES: To describe first dose and steady state antiretroviral drug exposure in the female genital tract. DESIGN: Non-blinded, single center, open-label pharmacokinetic study in HIV-infected women. METHOD: Twenty-seven women initiating combination antiretroviral therapy underwent comprehensive blood plasma and cervicovaginal fluid sampling for drug concentrations during the first dose of antiretroviral therapy and at steady-state. Drug concentrations were measured by validated HPLC/UV or HPLC-MS/MS methods. Pharmacokinetic parameters were estimated for 11 drugs by non-compartmental analysis. Descriptive statistics and 95% confidence intervals were generated using Intercooled STATA Release 8.0 (Stata Corporation, College Station, Texas, USA). RESULTS: For all antiretroviral drugs, genital tract concentrations were detected rapidly after the first dose. Drugs were stratified according to the genital tract concentrations achieved relative to blood plasma. Median rank order of highest to lowest genital tract concentrations relative to blood plasma at steady state were: lamivudine (concentrations achieved were 411% greater than blood plasma), emtricitabine (395%), zidovudine (235%) tenofovir (75%), ritonavir (26%), didanosine (21%), atazanavir (18%), lopinavir (8%), abacavir (8%), stavudine (5%), and efavirenz (0.4%). CONCLUSIONS: This is the first study to comprehensively evaluate antiretroviral drug exposure in the female genital tract. These findings support the use of lamivudine, zidovudine, tenofovir and emtricitabine as excellent pre exposure/post-exposure prophylaxis (PrEP/PEP) candidates. Atazanavir and lopinavir might be useful agents for these applications due to favorable therapeutic indices, despite lower genital tract concentrations. Agents such as stavudine, abacavir, and efavirenz that achieve genital tract exposures less than 10% of blood plasma are less attractive PrEP/PEP candidates. PMID- 17721098 TI - Safety and efficacy of sperm washing in HIV-1-serodiscordant couples where the male is infected: results from the European CREAThE network. AB - OBJECTIVE: To examine the safety and effectiveness of assisted reproduction using sperm washing for HIV-1-serodiscordant couples wishing to procreate where the male partner is infected. DESIGN AND METHODS: A retrospective multicentre study at eight centres adhering on the European network CREAThE and involving 1036 serodiscordant couples wishing to procreate. Sperm washing was used to obtain motile spermatozoa for 3390 assisted reproduction cycles (2840 intrauterine inseminations, 107 in-vitro fertilizations, 394 intra-cytoplasmic sperm injections and 49 frozen embryo transfers). An HIV test was performed in female partners at least 6 months after assisted reproduction attempt. The outcome measures recorded were number of assisted reproduction cycles, pregnancy outcome and HIV test on women post-treatment. RESULTS: A total of 580 pregnancies were obtained from 3315 cycles. Pregnancy outcome was unknown in 47 cases. The 533 pregnancies resulted in 410 deliveries and 463 live births. The result of female HIV testing after assisted reproduction was known in 967 out of 1036 woman (7.1% lost to follow-up). All tests recorded were negative. The calculated probability of contamination was equal to zero (95% confidence interval, 0-0.09%). CONCLUSION: This first multicentre retrospective study of assisted reproduction following sperm washing demonstrates the method to be effective and to significantly reduce HIV-1 transmission risk to the uninfected female partner. These results support the view that assisted reproduction with sperm washing could not be denied to serodiscordant couples in developed countries and, where possible, could perhaps be integrated into a global public health initiative against HIV in developing countries. PMID- 17721100 TI - A peer-education intervention to reduce injection risk behaviors for HIV and hepatitis C virus infection in young injection drug users. AB - OBJECTIVES: To evaluate whether a behavioral intervention, which taught peer education skills, could reduce injection and sexual risk behaviors associated with primary HIV and hepatitis C virus infection (HCV) among young injection drug users (IDU). DESIGN: We conducted a randomized controlled trial involving HIV and HCV antibody-negative IDU, aged 15-30 years, recruited in five United States cities. A six-session, small-group, cognitive behavioral, skills-building intervention in which participants were taught peer education skills (n = 431) was compared with a time-equivalent attention control (n = 423). Baseline visits included interviews for sociodemographic, psychosocial, and behavioral factors during the previous 3 months; HIV and HCV antibody testing; and pre/posttest counselling. Procedures were repeated 3 and 6 months postintervention. RESULTS: The intervention produced a 29% greater decline in overall injection risk 6 months postintervention relative to the control [proportional odds ratio 0.71; 95% confidence limit (CL) 0.52, 0.97], and a 76% decrease compared with baseline. Decreases were also observed for sexual risk behaviors, but they did not differ by trial arm. Overall HCV infection incidence (18.4/100 person-years) did not differ significantly across trial arms (relative risk 1.15; 95% CL 0.72, 1.82). No HIV seroconversions were observed. CONCLUSION: Interventions providing information, enhancing risk-reduction skills, and motivating behavior change through peer education training can reduce injection risk behaviors, although risk elimination might be necessary to prevent HCV transmission. PMID- 17721099 TI - The prevalence and incidence of neurocognitive impairment in the HAART era. AB - OBJECTIVES: HAART suppresses HIV viral replication and restores immune function. The effects of HAART on neurological disease are less well understood. The aim of this study was to assess the prevalence and incidence of neurocognitive impairment in individuals who initiated HAART as part of an AIDS clinical trial. DESIGN: A prospective cohort study of HIV-positive patients enrolled in randomized antiretroviral trials, the AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) study. METHODS: We examined the association between baseline and demographic characteristics and neurocognitive impairment among 1160 subjects enrolled in the ALLRT study. RESULTS: A history of immunosuppression (nadir CD4 cell count < 200 cells/microl) was associated with an increase in prevalent neurocognitive impairment. There were no significant virological and immunological predictors of incident neurocognitive impairment. Current immune status (low CD4 cell count) was associated with sustained prevalent impairment. CONCLUSION: The association of previous advanced immunosuppression with prevalent and sustained impairment suggests that there is a non-reversible component of neural injury that tracks with a history of disease progression. The association of sustained impairment with worse current immune status (low CD4 cell count) suggests that restoring immunocompetence increases the likelihood of neurocognitive recovery. Finally, the lack of association between incident neurocognitive impairment and virological and immunological indicators implies that neural injury continues in some patients regardless of the success of antiretroviral therapy on these laboratory measures. PMID- 17721101 TI - Association of cutaneous anergy with human papillomavirus and cervical neoplasia in HIV-seropositive and seronegative women. AB - OBJECTIVE: Cutaneous anergy testing evaluates delayed type hypersensitivity responses and is, in essence, an in-vivo measure of cell-mediated immune function at an epithelial surface. This study assessed the relationship of anergy test results with cervical infection by human papillomavirus (HPV) and cervical neoplasia in HIV-seropositive and seronegative women. METHODS: HIV-seropositive (n = 1029) and HIV-seronegative (n = 272) women enrolled in a long-term cohort study were followed semi-annually with HPV-DNA testing and cytology. Anergy was defined as unresponsiveness to Candida albicans, tetanus toxoid, and mumps antigen. RESULTS: Anergy was associated with the prevalent detection of squamous intraepithelial lesions [SIL; adjusted odds ratio 1.70; 95% confidence interval (CI) 1.16-2.48] in multivariable logistic regression models, and with the incident detection of oncogenic HPV (adjusted hazard ratio 1.24; 95% CI 0.99 1.56) in multivariable Cox regression models. These models adjusted for HIV infection, combined CD4 T-cell and HIV-RNA strata (13 separate strata to control optimally for their interactive effects), as well as other variables. CONCLUSION: Cutaneous anergy testing may measure aspects of local cellular immune function in epithelial tissues that are important for the control of HPV and development of SIL, and that in HIV-seropositive women are not fully accounted for by circulating CD4 T-cell counts and HIV-RNA levels. PMID- 17721102 TI - Biological and behavioural impact of an adolescent sexual health intervention in Tanzania: a community-randomized trial. AB - OBJECTIVE: The impact of a multicomponent intervention programme on the sexual health of adolescents was assessed in rural Tanzania. DESIGN: A community randomized trial. METHODS: Twenty communities were randomly allocated to receive either a specially designed programme of interventions (intervention group) or standard activities (comparison group). The intervention had four components: community activities; teacher-led, peer-assisted sexual health education in years 5-7 of primary school; training and supervision of health workers to provide 'youth-friendly' sexual health services; and peer condom social marketing. Impacts on HIV incidence, herpes simplex virus 2 (HSV2) and other sexual health outcomes were evaluated over approximately 3 years in 9645 adolescents recruited in late 1998 before entering years 5, 6 or 7 of primary school. RESULTS: The intervention had a significant impact on knowledge and reported attitudes, reported sexually transmitted infection symptoms, and several behavioural outcomes. Only five HIV seroconversions occurred in boys, whereas in girls the adjusted rate ratio (intervention versus comparison) was 0.75 [95% confidence interval (CI) 0.34, 1.66]. Overall HSV2 prevalences at follow-up were 11.9% in male and 21.1% in female participants, with adjusted prevalence ratios of 0.92 (CI 0.69, 1.22) and 1.05 (CI 0.83, 1.32), respectively. There was no consistent beneficial or adverse impact on other biological outcomes. The beneficial impact on knowledge and reported attitudes was confirmed by results of a school examination in a separate group of students in mid-2002. CONCLUSION: The intervention substantially improved knowledge, reported attitudes and some reported sexual behaviours, especially in boys, but had no consistent impact on biological outcomes within the 3-year trial period. PMID- 17721103 TI - Risk of cancers during interrupted antiretroviral therapy in the SMART study. AB - OBJECTIVE: To compare rates of AIDS-defining and non-AIDS-defining malignancies between patients on a CD4 T-cell-guided antiretroviral therapy (ART) strategy and continuous ART. DESIGN: A randomized clinical trial. METHODS: Malignancy rates were compared between the drug conservation arm in which ART was stopped if the CD4 T-cell count exceeded 350 cells/microl and (re)started if it fell to less than 250 cells/microl and the viral suppression arm utilizing continuous ART. Cox models were used to examine baseline characteristics including age, sex, race, cigarette use, previous malignancies, CD4 T-cell and HIV-RNA levels, hepatitis B or C, and ART duration. RESULTS: A total of 5472 participants were randomly assigned to treatment groups, of whom 70 developed cancer: 13 AIDS-defining malignancies and 58 non-AIDS-defining malignancies (one patient had both). The AIDS-defining malignancy rate per 1000 person-years was higher in the drug conservation arm (3.0 versus 0.5). Proximal CD4 T-cell and HIV RNA levels mediated much of this increased risk. The drug conservation arm also had higher rates of Kaposi's sarcoma (1.9 versus 0.3) and lymphoma (Hodgkin's and non Hodgkin's; 1.1 versus 0.3). The non-AIDS-defining malignancy rate was similar between the drug conservation and viral suppression arms (8.8 versus 7.1). The most common non-AIDS-defining malignancies were skin (n = 16), lung (n = 8) and prostate (n = 6) cancers. CONCLUSION: Non-AIDS-defining malignancies were more common in this cohort than AIDS-defining malignancies. This analysis provides further evidence against the use of CD4 T-cell-guided ART because of a higher risk of AIDS-defining malignancies in addition to opportunistic infections and deaths. PMID- 17721104 TI - HAD and the need for new trial design methodology. PMID- 17721105 TI - Preventing hepatitis C virus infection in injection drug users: risk reduction is not enough. PMID- 17721106 TI - AIDS-associated central nervous system cryptococcosis: a Brazilian case study. AB - In recent years the effect of HAART in patients with AIDS has been great at decreasing the incidence of opportunistic infections. Nonetheless, patients with AIDS living in developing countries still present with severe central nervous system cryptococcosis, with high mortality rates. The study of the clinical epidemiological-laboratory aspects of the patients treated before the HAART era might be useful in an assessment of the impact of these drugs in the prognosis of cases. PMID- 17721107 TI - Early virological response of zidovudine/lamivudine/abacavir for patients co infected with HIV and tuberculosis in Uganda. AB - Triple nucleoside reverse transcriptase inhibitors are recommended as an alternative regimen for HIV-infected patients undergoing tuberculosis treatment in resource-limited settings. Few data exist on the efficacy of such regimens in tuberculosis patients. In 34 tuberculosis/HIV-co-infected patients treated with zidovudine/lamivudine/abacavir, 76% achieved HIV RNA less than 50 copies/ml at 24 weeks. No cases of hypersensitivity or immune reconstitution syndrome were observed. These data support the continuing evaluation of nucleoside-based antiretroviral regimens as an alternative treatment for this population. PMID- 17721108 TI - Virological fitness of HIV in patients with resistance to enfuvirtide. AB - Resistance to the HIV fusion inhibitor enfuvirtide is associated with mutations in the first heptad repeat region of gp41, but little is known of their impact on replicative fitness in vivo. We followed seven patients undergoing salvage therapy that included enfuvirtide in order to document the temporal generation of genotypic and phenotypic resistance in parallel with replicative fitness. Resistance to enfuvirtide was not associated with decreased replicative fitness of HIV strains infecting these patients. PMID- 17721109 TI - Combined tipranavir and enfuvirtide use associated with higher plasma tipranavir concentrations but not with increased hepatotoxicity: sub-analysis from RESIST. AB - In RESIST, enfuvirtide co-administered with ritonavir-boosted tipranavir was associated with higher plasma tipranavir concentrations, which seldom rose above those associated with an increased risk of grade 3/4 transaminase elevations. Transaminase elevation rates (6.5%) and clinical hepatic event rates (5.9 events/100 person exposure years) were lower in the tipranavir/ritonavir with enfuvirtide group than in the tipranavir/ritonavir without enfuvirtide group. Observed increases in plasma tipranavir concentrations thus had no apparent effect on the risk of hepatotoxicity. PMID- 17721110 TI - Cytokine pattern in Kaposi's sarcoma associated with immune restoration disease in HIV and tuberculosis co-infected patients. AB - We analysed the evolution of different cytokines (IL-4, IL-6, tumour necrosis factor alpha and vascular endothelial growth factor; VEGF) involved in the development of Kaposi's sarcoma in two patients in whom HIV infection presented with disseminated Mycobacterium tuberculosis infection. They simultaneously developed tuberculosis-associated immune restoration disease and Kaposi's sarcoma shortly after the initiation of HAART. Analysis of VEGF and pro-inflammatory cytokines led us to hypothesize that Kaposi's sarcoma could be promoted by the tuberculosis immune response. PMID- 17721111 TI - Immune reconstitution syndrome to Strongyloides stercoralis syndrome: authors' response. PMID- 17721112 TI - Promoting circumcision for HIV-positive men. PMID- 17721113 TI - Schistosomiasis and immune reconstitution disease. PMID- 17721114 TI - Movement and extrapyramidal disorders associated with interferon use in HIV/hepatitis C coinfection. PMID- 17721115 TI - Carotid intima-media thickness course in HIV-infected patients: beyond classical cardiovascular risk factors. PMID- 17721116 TI - Aspergillus galactomannan antigenemia in penicilliosis marneffei. PMID- 17721117 TI - Blood pressure and antiretroviral therapy. PMID- 17721119 TI - Diffuse interstitial pulmonary opacities induced by nevirapine. PMID- 17721118 TI - Efavirenz urolithiasis. PMID- 17721120 TI - High impact of mobile units for mass HIV testing in Africa. PMID- 17721121 TI - On our shoulders. PMID- 17721122 TI - The clinical research nurse. PMID- 17721131 TI - Communicating competence. PMID- 17721132 TI - Separate organizations. PMID- 17721146 TI - Paid sick leave, anyone? PMID- 17721144 TI - The personal health record. PMID- 17721147 TI - Surviving orientation. PMID- 17721148 TI - Preventing contrast medium-induced nephropathy. PMID- 17721150 TI - Unwanted treatment. PMID- 17721151 TI - Smoked out: emergency evacuation of an ICU. PMID- 17721152 TI - Newly licensed RNs' characteristics, work attitudes, and intentions to work. AB - OBJECTIVE: In an effort to better understand turnover rates in hospitals and the effect of new nurses on them, this study sought to describe the characteristics and attitudes toward work of newly licensed RNs, a population important to both the nursing profession and the health care system. METHODS: A survey was mailed to a random sample of new RNs in 35 states and the District of Columbia. A total of 3,266 returned surveys met the inclusion criteria, for a response rate of 56%. RNs who qualified had completed the licensing examination and obtained a first license between August 1, 2004, and July 31, 2005. Data pertaining to four areas were collected: respondent characteristics, work-setting characteristics, respondents' attitudes toward work, and job opportunities. Respondents who were not working were asked to specify why. RESULTS: Of the eligible newly licensed RNs, 58.1% had an associate's degree, 37.6% had a bachelor's degree, and 4.3% had a diploma or a master's or higher degree as their first professional degree. They were generally pleased with their work groups but felt they had only moderate support from supervisors. About 13% had changed principal jobs after one year, and 37% reported that they felt ready to change jobs. More than half of the respondents (51%) worked voluntary overtime, and almost 13% worked mandatory overtime. Also, 25% reported at least one on-the-job needlestick in a year; 39%, at least one strain or sprain; 21%, a cut or laceration; and 46%, a bruise or contusion; 62% reported experiencing verbal abuse. A quarter of them found it "difficult or impossible" to do their jobs at least once per week because of inadequate supplies. CONCLUSIONS: This study provides descriptive evidence that a majority of newly licensed RNs are reasonably satisfied and have no plans to change jobs, but the group is not homogeneous. The negative attitudes expressed in response to some survey questions suggest that newly licensed RNs may not remain in the acute care settings where they start out. Investing in better orientation and management may be the key to retaining them in hospitals. The authors will be following these RNs for two years and will develop predictive models of turnover rates. PMID- 17721155 TI - When standards of care change in mass-casualty events. PMID- 17721158 TI - A national solution to patient handling injuries. PMID- 17721160 TI - 'The best worst job I've ever had'. PMID- 17721163 TI - Gunshot residue testing in suicides: Part I: Analysis by scanning electron microscopy with energy-dispersive X-ray. AB - Several different methods can be employed to test for gunshot residue (GSR) on a deceased person's hands, including scanning electron microscopy with energy dispersive x-ray spectroscopy (SEM-EDX) and inductively coupled plasma-atomic emission spectrometry (ICP-AES). Each of these techniques has been extensively studied, especially on living individuals. The current studies (Part I and Part II) were designed to compare the use and utility of the different GSR testing techniques in a medical examiner setting. In Part I, the hands of deceased persons who died from undisputed suicidal handgun wounds were tested for GSR by SEM-EDX over a 4-year period. A total of 116 cases were studied and analyzed for caliber of weapon, proximity of wound, and results of GSR testing, including spatial deposition upon the hands. It was found that in only 50% of cases with a known self-inflicted gunshot wound was SEM-EDX positive for at least 1 specific particle for GSR. In 18% of the cases there was a discernible pattern (spatial distribution) of the particles on the hand such that the manner in which the weapon was held could be determined. Since only 50% of cases where the person is known to have fired a weapon immediately prior to death were positive for GSR by SEM-EDX, this test should not be relied upon to determine whether a deceased individual has discharged a firearm. Furthermore, in only 18% of cases was a discernible pattern present indicating how the firearm was held. The low sensitivity, along with the low percentage of cases with a discernible pattern, limits the usefulness of GSR test results by SEM-EDX in differentiating self inflicted from non-self-inflicted wounds. PMID- 17721164 TI - Gunshot residue testing in suicides: Part II: Analysis by inductive coupled plasma-atomic emission spectrometry. AB - Several different methods can be employed to test for gunshot residue (GSR) on a decedent's hands, including scanning electron microscopy with energy dispersive x ray (SEM/EDX) and inductive coupled plasma-atomic emission spectrometry (ICP AES). In part I of this 2-part series, GSR results performed by SEM/EDX in undisputed cases of suicidal handgun wounds were studied. In part II, the same population was studied, deceased persons with undisputed suicidal handgun wounds, but GSR testing was performed using ICP-AES. A total of 102 cases were studied and analyzed for caliber of weapon, proximity of wound, and the results of the GSR testing. This study found that 50% of cases where the deceased was known to have fired a handgun immediately prior to death had positive GSR results by ICP/AES, which did not differ from the results of GSR testing by SEM/EDX. Since only 50% of cases where the person is known to have fired a weapon were positive for GSR by either method, this test should not be relied upon to determine whether someone has discharged a firearm and is not useful as a determining factor of whether or not a wound is self-inflicted or non-self-inflicted. While a positive GSR result may be of use, a negative result is not helpful in the medical examiner setting as a negative result indicates that either a person fired a weapon prior to death or a person did not fire a weapon prior to death. PMID- 17721165 TI - Can the direct cardiac effects of the electric pulses generated by the TASER X26 cause immediate or delayed sudden cardiac arrest in normal adults? AB - There is only a small amount of experimental data about whether the TASER X26, a nonlethal weapon that delivers a series of brief electrical pulses to cause involuntary muscular contraction to temporarily incapacitate an individual, can initiate ventricular fibrillation to cause sudden cardiac arrest either immediately or sometime after its use. Therefore, this paper uses the fundamental law of electrostimulation and experimental data from the literature to estimate the likelihood of such events. Because of the short duration of the TASER pulses, the large duration of the cardiac cell membrane time constant, the small fraction of current from electrodes on the body surface that passes through the heart, and the resultant high pacing threshold from the body surface, the fundamental law of electrostimulation predicts that the TASER pulses will not stimulate an ectopic beat in the large majority of normal adults. Since the immediate initiation of ventricular fibrillation in a normal heart requires a very premature stimulated ectopic beat and the threshold for such premature beats is higher than less premature beats, it is unlikely that TASER pulses can immediately initiate ventricular fibrillation in such individuals through the direct effect of the electric field generated through the heart by the TASER. In the absence of preexisting heart disease, the delayed development of ventricular fibrillation requires the electrical stimuli to cause electroporation or myocardial necrosis. However, the electrical thresholds for electroporation and necrosis are many times higher than that required to stimulate an ectopic beat. Therefore, it is highly unlikely that the TASER X26 can cause ventricular fibrillation minutes to hours after its use through direct cardiac effects of the electric field generated by the TASER. PMID- 17721166 TI - National Association of Medical Examiners position paper on the medical examiner release of organs and tissues for transplantation. AB - The medical examiner community plays a key role in the organ and tissue procurement process for transplantation. Since many, if not most, potential organ or tissue donors fall under medicolegal jurisdiction, the medical examiner bears responsibility to authorize or deny the procurement of organs or tissues on a case-by-case basis. This responsibility engenders a basic dichotomy for the medical examiner's decision-making process. In cases falling under his/her jurisdiction, the medical examiner must balance the medicolegal responsibility centered on the decedent with the societal responsibility to respect the wishes of the decedent and/or next of kin to help living patients. Much has been written on this complex issue in both the forensic pathology and the transplantation literature. Several studies and surveys of medical examiner practices, as well as suggested protocols for handling certain types of cases, are available for reference when concerns arise that procurement may potentially hinder medicolegal death investigation. It is the position of the National Association of Medical Examiners (NAME) that the procurement of organs and/or tissues for transplantation can be accomplished in virtually all cases, without detriment to evidence collection, postmortem examination, determination of cause and manner of death, or the conducting of criminal or civil legal proceedings. The purpose of this position paper is to review the available data, the arguments for and against medical examiner release, and to encourage the release of organs and tissues in all but the rarest of circumstances. PMID- 17721167 TI - Unsuspected central nervous system gummas in a case of "cerebral infarct" associated with cocaine use. AB - A 54-year-old African-American male was hospitalized with a left "cerebrovascular accident," altered mental status, agitation, rhabdomyolysis, and hypernatremia. Laboratory tests found cocaine in his system and a positive RPR (rapid plasmin reagin test). A CAT (computed axial tomography) scan without contrast taken 8 days prior to his death showed a left middle cerebral artery infarct, with edema and mass effect, and a 1-cm midline shift to the right. He underwent symptomatic treatment, eventually suffered cardiopulmonary arrest and multiorgan failure, and expired 8 days after admission. The left cerebral lesion diagnosed clinically as a cerebral infarct was actually determined to be a syphilitic gumma on postmortem neuropathologic examination. Neurosyphilis, although rare, should be considered in the differential diagnosis of space-occupying lesions in the brain because cases of syphilis continue to occur both sporadically and as an opportunistic infection associated with acquired immunodeficiency syndrome (AIDS) and because neurosyphilis is treatable. PMID- 17721168 TI - A fatal case of hypovolemic shock after cesarean section. AB - We report a fatal case of hypovolemic shock caused by uncontrollable hemorrhaging after emergency cesarean section. In this patient, the incision in the uterus was located only 1 cm from the cervical os. We suspect that this close incision was the cause of the damage to the uterine venous plexus and the bleeding. We discuss the cause of death and offer advice on performing autopsies in patients who have died of bleeding after cesarean section. PMID- 17721169 TI - Metastatic cancer of the urinary bladder: can it be a nonnatural death? AB - Deaths from metastatic carcinoma are almost exclusively viewed as wholly natural deaths. However, if it can be shown that a cancer has arisen as a result of a prior traumatic injury and the body's healing response to the injury, or treatment thereof, then in select cases, the manner of death shall reflect that of the precipitating injury. This case report is that of a woman who was rendered quadriplegic from spinal cord injury sustained in a motor vehicle crash when she was 22 years old. She died at the age of 49 years from widely metastatic squamous cell carcinoma of the urinary bladder. Her bladder cancer most likely arose from decades-long chronic irritation of the bladder epithelium by physical contact with an indwelling Foley catheter and urinary infections. Over the years, the chronic bladder irritation likely precipitated metaplastic, dysplastic, and finally neoplastic changes of the bladder epithelium, providing a link between her spinal cord injury, the indwelling Foley catheter, and her bladder cancer, engendering an accidental manner of death. The manner of death reflected the circumstances of her injury that predisposed her to the cancer that eventually caused her death. PMID- 17721170 TI - Firearm suicide committed using an unusual combination of tandem missiles: a bullet, a nail, and a screw. AB - An interesting case of firearm suicide carried out using an unusual type of handmade weapon and a peculiar combination of tandem missiles is presented. A nail and a screw were placed in the rifle barrel ahead of a bullet, and all 3 were simultaneously discharged. The inflicted injury began with 1 common channel, which later split in 2 separate channels, both directed backwards and upwards; one was caused by the screw, ending in the epistropheal body, and the other, caused by the bullet and the nail, penetrated into the cranial cavity, where it bifurcated in 2 branches, one from the bullet, ending in the cerebellar tissue, and the other from the nail, penetrated through the brain stem. The established site of the entrance suicidal wound, the appearance of the weapon, and the unusual missiles are discussed with regard to the available references dealing with different types of nail injuries to the head. PMID- 17721171 TI - Sellar fracture followed by sudden death: an autopsy case. AB - The authors describe a case of sellar fracture followed by sudden death. The victim was involved in a wrangle. The autopsy revealed facial damage and sellar fracture and no evidence of cerebral damage, except for a mild subarachnoid hemorrhage in the left parietotemporal regions and undersurface of both frontal lobes. Sellar fracture is a rare and severe entity, associated with serious complications, which is frequently diagnosed postmortem. In any case, death is rarely a direct consequence of the sellar fracture itself and is usually considered to be the result of associated cerebral trauma. This case prompted us to screen the literature on sellar fracture to gain a better understanding of the mechanism of death. PMID- 17721172 TI - Nontraumatic intracranial epidural hematoma: a case report. AB - An outwardly mummified and inwardly badly decomposed body was found in a garage. At autopsy, no injuries were detected. Apart from coronary heart disease, with an old myocardial scar and a hepatic steatosis, the most striking finding was a large intracranial epidural hemorrhage situated at the left frontal lobe. As a relevant traumatic genesis could be ruled out, we deemed this a nontraumatic epidural hematoma. This finding is extremely rare. Several underlying disorders have been discussed as causes of spontaneous epidural hematomas. In this presented case, the authors discuss possible etiological factors. PMID- 17721173 TI - Fatal biliary peritonitis due to postinsertion migration of a Robinson drain tip, with erosion into the liver parenchyma. AB - Iatrogenic injury due to incorrectly sited drains and tubes is a rare but recognized complication and can occur at many different sites. Migration of correctly sited drains and tubes is rarer still. A handful of rare cases involving longstanding ventriculoperitoneal and lumboperitoneal shunts migrating and causing perforation of the bowel exist, often complicated by central nervous system sepsis. We present a previously unreported complication of a Robinson drain, one of 2 abdominal drains inserted under direct vision during a subtotal gastrectomy for carcinoma, in a frail 78-year-old woman. Twenty-four days postoperatively, after a period of predictably slow but steady recovery, bile stained fluid was noted in the drain. Unfortunately, the patient rapidly deteriorated and died. Autopsy revealed multiorgan failure due to peritonitis. Both drains were noted to be correctly and firmly sutured to the skin. The tip of the right-sided Robinson drain was found to have migrated, eroding into the liver parenchyma, resulting in biliary peritonitis. The left-sided Robinson drain was correctly sited in the peritoneal cavity. We present the postmortem findings and a review of the literature. PMID- 17721174 TI - Hanging deaths with bound hands: what is the manner? AB - In Franklin County, Ohio, 3 cases of hangings with bound hands were reported in a 4-month period in 2005. All of the victims were men. In 2 of the 3 cases, the hands were bound behind the back. One victim bound his hands in front of his body. In each case, the police ruled the deaths "suspicious" due to the fact that the victims' hands were bound. Complete investigation is required. Only after a thorough scene investigation, medicolegal autopsy, and knowledge of recent circumstances of the decedent's life can a determination of manner be made. PMID- 17721175 TI - Arrhythmogenic right ventricular dysplasia cases in forensic autopsies. AB - Arrhythmogenic right ventricular dysplasia or cardiomyopathy (ARVD or ARVC) is an increasingly recognized entity with clinical and forensic implications. This is the first series documenting ARVD in 5 separate cases in forensic autopsies from Turkey declared as natural sudden cardiac death following complete autopsy and toxicologic analysis. There was a male preponderance (M/F=4), with a mean age of 50. PMID- 17721176 TI - Age estimation from root development of mandibular third molars in comparison with skeletal age of wrist joint. AB - Identification of the living person and the dead is of paramount importance for variety of reasons in forensic practice routinely. Age estimation is one of the prime factors employed to establish identity. Estimating age from teeth is generally reliable as they are naturally preserved long after all the tissues and even bones have disintegrated. A study was done to determine the age by root developmental changes, using the intraoral periapical radiographs of the mandibular third molars, adopting the Leif Kullman et al method. Three hundred forty-six girls and 389 boys of the age range 15-25 years, among the South Indian population of young adults from various schools and colleges in the vicinity of Dakshina Kannada and Udupi Districts and also among the patients visiting the outpatient department of Oral Medicine and Radiology, College of Dental Surgery, Manipal, were considered for this study. The subjects were roentgenographically examined to determine the age from the 7 stages of root development of the left mandibular third molar. Depending on the exact stage of root development as seen in the radiograph, the chronologic age was determined. This method sheds a new light on determining the ages of 15, 16, and 18 years, which has an immense medicolegal bearing. PMID- 17721177 TI - The prevalence of drugs in carbon monoxide-related deaths: a retrospective study, 2000-2003. AB - The objective of this study was to review demographic characteristics and drugs detected in carbon monoxide (CO)-related deaths from cases received by the Office of the Cuyahoga County Coroner in Cleveland, Ohio, from 2000-2003. Postmortem reports were reviewed, and decedents for which CO was listed as the cause of death were included. The data were compiled into 3 groups according to the official coroner's verdict as to the manner of death: accident, suicide, and homicide. Included in this study were 122 cases: 84 (69%) accidental, 31 (25%) suicide, and 7 (6%) homicide. Accident decedents were typically white males, aged 40-59 years, residing in Cleveland. Suicide decedents were also middle-aged, white males but residing in the suburbs. Homicide decedents under the age of 6 were characteristically black (N=2), while decedents over the age of 39 were predominately white (N=3). Carboxyhemoglobin (COHb) levels in suicide cases were higher than concentrations measured in accidental deaths. The highest percentage of suicide decedents (36%) had a COHb level>70% saturation, accident decedents (36%) between 50% and 69% saturation, and homicide decedents (71%) below 50% saturation. Ethanol (N=34) was detected in 28% of deaths, and therapeutic and/or abused drugs (N=50) were detected in 41% of deaths. Illicit drugs were detected in 11% of cases (cocaine/metabolites; THC/metabolites), other drug positives were therapeutic medications. The most common drugs detected were antidepressants and antihistamines in suicides and pain medications and antihistamines in accidents. PMID- 17721178 TI - Polysarcia adiposa: morbid obesity. AB - From October 1988 to March 2005, there were at least 92 autopsy cases where morbid obesity was present and/or where it was attributed to the cause of death in the coronial district of Auckland, New Zealand, a city with a population of over 1 million people. Obesity has been researched internationally, and much is known about associated comorbidities such as atherosclerotic disease, hypertension, and diabetes, to name a few. However, in the morbidly obese (body mass index>or=40 kg/m2), only 14 of 92 cases were found to have ischemic heart disease due to coronary atherosclerosis as the principal cause of death, and slightly over half (48/92) have some degree (mild, moderate, severe) of coronary atheroma. There is a strong positive correlation between heart weight and body weight. Only 8 livers were normal, all others showing some form of steatosis, venous congestion, and fibrosis/cirrhosis. The mean weights of the heart, lungs, and liver were above the normal reference range in almost all cases. In conclusion, the study did not follow the widely published finding of the positive correlation between morbid obesity and ischemic heart disease in terms of mortality, but the study was consistent with other studies on the organ manifestations of morbid obesity, particularly for the heart, lungs, and liver. PMID- 17721179 TI - Symmetrical "mirror-image" injuries and the "chessboard" pattern: useful markers of self-mutilation. AB - The evaluation of injuries due to self-mutilation may be complicated by atypical lesions and fabricated histories of the causative events. Four cases are described where one of the most striking findings was the presence of "mirror image" injuries and/or a "chessboard" pattern of intersecting parallel lines from self-inflicted incised wounds. Case 1: A 32-year-old man was dead in his burnt out car, with symmetrical, "mirror-image", circular burns from the car cigarette lighter over his forehead, cheeks, ears, upper and lower arms, the dorsal and palmar aspects of the hands, the anterior chest wall including the nipples, the anterior abdomen, thighs, lower legs, and the back of his neck. The deceased had a history of psychotic depression and had died of burns and inhalation of products of combustion. Case 2: A 19-year-old woman who fabricated a history of assault demonstrated multiple, superficial, "mirror-image" injuries of her thighs and forearms. Case 3: A 32-year-old man who exsanguinated from cut wrists showed multiple, superficial, and "mirror-image" incised wounds of the wrists, with a "chessboard" pattern. Case 4: A 26-year-old man died after jumping from a building. He had multiple superficial, "mirror-image" incised wounds of his anterior chest and thighs, with a typical "chessboard" pattern. Given the difficulties that sometimes arise in determining whether injuries have been self inflicted or not, the finding of symmetrical "mirror-image" injuries, and/or a "chessboard" pattern formed by 2 groups of regular, parallel, superficial incised wounds running at right angles to each other provides compelling evidence of self mutilation, unless a plausible alternative explanation is available. PMID- 17721180 TI - A fatal doxepin poisoning associated with a defective CYP2D6 genotype. AB - It has been suggested that the polymorphism of the CYP2D6 gene can contribute to occurrence of fatal adverse effects. We therefore investigated postmortem toxicology cases of fatal drug poisonings related to CYP2D6 substrates, with the manner of death denoted as accidental or undetermined. CYP2D6 genotypes were determined in 11 consecutive cases with samples available for DNA analysis. A case of fatal doxepin poisoning with an undetermined manner of death was found to coincide with a completely nonfunctional CYP2D6 genotype (*3/*4), indicating a total absence of CYP2D6 enzyme and suggesting a poor metabolizer phenotype. The doxepin concentration was 2.4 mg/L, the concentration of nordoxepin 2.9 mg/L, and the doxepin/nordoxepin ratio 0.83, the lowest found among the 35 nordoxepin positive postmortem cases analyzed during the same year. No alcohols or other drugs were detected in the case. The CYP2C19 genotype was determined as that of an extensive metabolizer. The high N-desmethylmetabolite concentration is not consistent with acute intoxication. It is therefore probable that the defective genotype has contributed to the death, possibly involving repeated high dosage of doxepin. Our case strongly emphasizes that a pharmacogenetic analysis in postmortem forensic setting may reveal new insight to the cause or manner of death. PMID- 17721181 TI - Toxicologic aspects of deaths due to falls from height. AB - A prospective study of 161 victims of falls from height is reported. The aim was to determine the interest of systematic qualitative and quantitative toxicological analysis in such fatalities. The primary cause of death was suicide (84.5%), followed by accidents (7%) and homicide (1%). In the remaining 7.5%, cause of death was undetermined. In the suicides, there was evidence of psychotropic medicines in 57% of the observations, with a much higher proportion of benzodiazepines and antidepressants in women than in men. Quantitative toxicologic analysis showed overdosing on medication in 16 suicide victims, with toxic levels in 11 of these. Systematic qualitative and quantitative toxicologic analysis made a significant contribution to the diagnosis of suicide by revealing either an unknown psychiatric treatment or a toxic level. PMID- 17721182 TI - Acute pancreatitis presenting as sudden, unexpected death: an autopsy-based study of 27 cases. AB - Acute pancreatitis represents a spectrum of disease, ranging from a mild, transitory illness to a severe, rapidly progressive hemorrhagic form, with massive necrosis and mortality rates of up to 24%. The reported incidence of acute pancreatitis diagnosed first at clinicopathologic autopsy ranges between 30% and 42%. To better describe outpatient fatalities due to acute pancreatitis that present as sudden, unexpected death, we retrospectively reviewed the autopsy files at the Institute of Legal Medicine, University of Hamburg, Germany, from 2000-2004. Individual cases were analyzed for sex, age, race, circumstances of death, social background of the deceased and previous medical history, seasonal occurrence of the disease, blood alcohol concentration at the time of death, body mass index, autopsy findings, histopathology, and etiology of acute pancreatitis. Among the 6178 autopsies carried out during the 5-year period evaluated, there were 27 cases of acute pancreatitis that presented as sudden, unexpected death. In all cases, the diagnosis was first made at autopsy. The male:female ratio was 1.7:1 and the mean age was 52 years (range, 30-91 years). Etiologies of acute pancreatitis included alcohol (n=19), gall stones (n=2), other identified etiologic factors (n=3), and idiopathic (n=3). Complications of acute pancreatitis included lung edema and/or acute respiratory distress syndrome, peritonitis, disseminated intravascular coagulation, and sepsis. At least 20 subjects (74%) had lived isolated, with no social contacts. Contrary to the clinical observations of a clear seasonal variation in the onset of acute pancreatitis, we found no correlation between death due to acute pancreatitis and a specific month or season. Many prior studies have suggested that the majority of deaths in severe acute pancreatitis occur in the late phase of the disease as a result of pancreatic sepsis. Conversely, in the present study, the majority of affected individuals died during the very early phase of the disease. While gallstones represent the main etiologic factor in most larger clinical series, biliary etiology seems to play only a minor role in outpatient deaths undergoing medicolegal autopsies. Data derived from medicolegal autopsy studies should be included in future population-based studies of acute pancreatitis. PMID- 17721183 TI - A functional approach to sudden unexplained infant deaths. AB - There is a great deal of variation in the methods and wording used by medical examiners in the medicolegal investigation and certification of infant deaths. This paper was created by the NAME Ad Hoc Committee on Sudden Unexplained Infant Death to address several specific issues, namely: * To establish a functional approach to the investigation of sudden unexplained infant deaths; * To outline a "bare minimum" set of recommendations to define the scope of investigation required; * To recommend methods and wording to be used when certifying infant deaths; * To develop a list of potential stressors or possible external causes of death that should be identified and reported on the death certificate and/or within a medical examiner/coroner office database. This paper was electronically posted for NAME member review and comment for a period of 30 days. The paper was further revised based on member comments and then submitted to the NAME board of directors in the fall of 2005 prior to the annual meeting. This text of this paper was officially approved and endorsed by the NAME board of directors on October 14, 2005, at the annual meeting in Los Angeles, CA. PMID- 17721184 TI - Detection of beta-catenin mutations in paraffin-embedded sporadic desmoid-type fibromatosis by mutation-specific restriction enzyme digestion (MSRED): an ancillary diagnostic tool. AB - Desmoid-type fibromatosis is a locally aggressive deep soft tissue tumor. Some cases are associated with adenosis polyposis coli germline mutations whereas others harbor somatic beta-catenin point mutations mainly in exon 3, codons 41 and 45. These mutations result in stabilization of beta-catenin, and activation of the Wnt signaling pathway. The aim of this study was to determine the specificity and sensitivity of these 3 most common beta-catenin mutations in the diagnosis of desmoid-type fibromatosis using paraffin-embedded material. The results were compared with nuclear expression of beta-catenin. Mutation-specific restriction enzyme digestion methodology was employed to detect the 3 mutations. One hundred and thirty-three cases were analyzed, including 76 desmoid-type, and 18 superficial fibromatosis, in addition to a further 39 fibromatosis mimics. A restriction site was present for analysis of the codon 41 mutation. Mismatch primers were designed for the codon 45 mutations. Mutations were detected in 66 cases (87%) of 76 desmoid-type fibromatosis (71 extra-abdominal). Of these, 34 (45%) were in codon 45 (TCT>TTT), 27 (35%) in codon 41 (ACC>GCC), and 5 (7%) in codon 45 (TCT>CCT). No mutations were detected in the other lesions studied. All desmoid-type fibromatosis cases and 72% of the mimics tested showed nuclear positivity for beta-catenin indicating immunohistochemistry is a sensitive but not a specific test for desmoid-type fibromatosis. In contrast, to date, beta catenin mutations have not been detected in any lesions which mimic desmoid-type fibromatosis. Mutation-specific restriction enzyme digestion, a simple and efficient means of detecting the common beta-catenin mutations in desmoid-type fibromatosis, complements light microscopy in reaching a diagnosis. PMID- 17721185 TI - Epstein-Barr virus negative clonal plasma cell proliferations and lymphomas in peripheral T-cell lymphomas: a phenomenon with distinctive clinicopathologic features. AB - Clonal B-cell populations have been described in peripheral T-cell lymphomas (PTCL) as secondary Epstein-Barr virus (EBV) driven B-cell expansions that may evolve to an overt B-cell lymphoma. EBV-negative B-cell proliferations associated with T-cell lymphomas are uncommon and not well characterized. We studied 15 patients who developed an EBV-negative B-cell proliferation or malignant lymphoma associated with PTCL. The T-cell tumors were 8 PTCL, not otherwise specified, 4 angioimmunoblastic T-cell lymphomas, and 3 cutaneous PTCL. The B-cell component was intermingled with the PTCL in all patients and it was classified as clonal/monotypic plasma cell proliferation in 8 lesions, clonal/monotypic large B cell proliferation in 4 patients, and B-cell lymphoma with plasmacytic/plasmablastic differentiation in 3 patients. Two patients had 2 clonally unrelated plasma cell proliferations associated with the same PTCL. All cases showed cytoplasmic Ig light chain restriction. Clonal IgH and T-cell receptor rearrangements were detected in 11/12 and 11/13 cases examined, respectively. EBV, cytomegalovirus, and HHV-8 were not observed in any of the examined cases. Sequential samples in 7 patients showed persistence of the PTCL and the B-cell component in 4, the PTCL without the B-cell lymphoma in 2, and progression of the B-cell neoplasm in 1. Patients followed an aggressive clinical course similar to conventional PTCL. In conclusion, EBV-negative clonal or mononotypic B-cell proliferations in patients with PTCL present with a spectrum of lesions ranging from plasma cell proliferations to overt lymphomas with plasmacytic/plasmablastic features. The distinctive features of these patients suggest that these lesions represent a specific phenomenon in PTCL. PMID- 17721186 TI - Primary mucin-producing urothelial-type adenocarcinoma of prostate: report of 15 cases. AB - Prostatic urothelial-type adenocarcinoma arises through a process of glandular metaplasia of the prostatic urethral urothelium and subsequent in situ adenocarcinoma sometimes associated with villous adenoma. These prostatic adenocarcinomas are analogous to nonurachal adenocarcinomas arising in the bladder from cystitis glandularis. Only 2 cases of urothelial-type adenocarcinoma from an institution other than our own have been previously described. The distinction between adenocarcinoma from another organ secondarily involving the prostate, usual adenocarcinoma of the prostate, and prostatic urothelial-type adenocarcinoma can present a significant diagnostic challenge and has significant therapeutic implications. Fifteen cases of prostatic urothelial-type adenocarcinoma were retrieved from the consult files of one of the authors. Mean patient age at diagnosis was 72 years (range 58 to 93 y). All men had negative colonoscopies, clinically excluding a colonic primary. Bladder primaries were ruled out clinically or pathologically in radical resection specimens. Follow-up was available on all men with a mean of 50.3 months (range 2 to 161 mo). All men presented with urinary obstruction symptoms with 3 (20%) also having mucusuria and 2 (13.3%) also having hematuria. Four men (26.7%) developed metastatic disease and 8 (53.3%) died of disease. In 8/15 (53%) cases, glandular metaplasia of the prostatic urethra and contiguous transition to adenocarcinoma were identified. Multiple histologic patterns were observed including dissection of the stroma by mucin pools 15/15 (100%), villous features 7/15 (47%), necrosis 2/15 (13.3%), signet ring cells 3/15 (20%), perineural invasion 1/15 (6.7%), focal squamous differentiation 1/15 (6.7%), and a granulomatous inflammatory response 1/15 (6.7%). Immunohistochemical stains were negative for prostate specific antigen, prostate specific acid phosphatase, CDX2, and beta-catenin in all cases. Stains were positive for high molecular weight cytokeratin in 12/12 cases (100%), and CK7 and CK20 in 10/12 cases (83.3%). Prostatic urothelial-type adenocarcinoma is a rare aggressive cancer arising in the prostate. The differential diagnosis includes conventional prostatic mucinous adenocarcinoma and secondary infiltration from a colonic or bladder adenocarcinoma. Immunohistochemistry for prostate specific antigen, prostate specific acid phosphatase, and high molecular weight cytokeratin along with morphology can help rule out conventional prostate carcinoma. beta-catenin, CDX2, and clinical studies are needed to rule out colonic adenocarcinoma. As prostatic urothelial type adenocarcinoma is entirely analogous to bladder adenocarcinoma in both, its morphology and immunophenotype, only clinical studies or in some cases pathologic examination of the cystoprostatectomy specimen can exclude infiltration from a primary bladder adenocarcinoma. PMID- 17721187 TI - Mucinous adenocarcinomas of the thymus: report of 2 cases and review of the literature. AB - BACKGROUND: Most adenocarcinomas of the mediastinum are metastatic lesions. Primary thymic adenocarcinomas are extremely rare neoplasms. We could find only 12 cases reported in the literature; of these 12, only 4 were of the mucinous subtype. DESIGN: We report 2 additional cases of the mucinous subtype, including a previously unreported mucinous variant with numerous psammoma bodies. RESULTS: The first case in a 61-year-old woman resembled a mucinous (colloid) carcinoma of other organs such as the breast and colon. It consisted of islands and strips of tumor cells floating in large pools of extracellular mucin. A unique feature of this tumor was the presence of numerous psammoma bodies. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) 7 and negative for CD5. The second case in an 82-year-old woman was a mucinous adenocarcinoma arising from a thymic cyst with areas of transition from benign to dysplastic epithelium. The tumor cells formed dilated glands, cords, and small nests that infiltrated the thymic cyst wall and exhibited evidence of mucin production. Immunohistochemically, the tumor cells were positive for CK 7 and focally positive for both CD5 and CK 5/6. CONCLUSIONS: Mucinous adenocarcinoma, with or without, psammoma bodies, may be of primary thymic origin and should be considered in the differential diagnosis of malignant mediastinal tumors. These 2 cases provide further documentation of the rare occurrence of primary mucinous adenocarcinomas of the thymic gland. PMID- 17721188 TI - BRAF in papillary thyroid carcinoma of ovary (struma ovarii). AB - BACKGROUND: Malignant struma ovarii (MSO) are rare tumors that arise from ectopic thyroid tissue in the ovary, benign struma ovarii (BSO). Most MSO are histologically classified as papillary thyroid carcinomas (PTC). Oncogenic activation of BRAF (35% to 69%), RAS (10%), or RET (5% to 30%) is common in PTC, and the mutations correlate with tumor subtype, patient age, and clinical behavior. In this study, we explored the possible role of these genes in the development of BSO and MSO. DESIGN: Six paraffin-embedded cases of MSO with histopathologic features of PTC (4 follicular variants, 1 classic, and 1 metastasis of a classic) and 9 BSO were identified. BRAF, NRAS, and KRAS mutations were evaluated using a combination of polymerase chain reaction, denaturing high performance liquid chromatography, and automated sequencing. RET alterations were screened by fluorescence in situ hybridization with multicolor probes. Corresponding benign tissues were evaluated when available. RESULTS: BRAF mutations were present in 4 of 6 MSO and none of 9 BSO. The BRAF mutations included V600E (2 cases), K601E, and a novel deletion/substitution TV599-600M. Neither MSO nor BSO contained alterations in NRAS, KRAS, or RET. CONCLUSIONS: The development of MSOs with PTC features is associated with BRAF mutations of the type commonly observed in PTC, suggesting a common pathogenesis for all PTCs regardless of location. In contrast, mutations in the RET/RAS/RAF pathway are not found in BSO. The prognostic significance of BRAF mutation status in MSO remains to be determined. PMID- 17721189 TI - Primary cardiac lymphoma: clinical, histologic, immunophenotypic, and genotypic features of 5 cases of a rare disorder. AB - Primary lymphomas of the heart are rare and frequently are diagnosed at autopsy. Modern imaging technology now permits early diagnosis and treatment. This report describes the clinical, histologic, immunophenotypic, and molecular genetic findings for 5 patients with malignant lymphoma restricted to the cardiac muscle, with or without pericardial involvement. All patients were women, with ages ranging from 40 to 68 years (median 55 y). The right atrium was involved in all cases with the left atrium, right ventricle, and pericardium affected in 1 case each. Clinical presentation included pericardial effusions associated with precordial pain, dyspnea, and bradycardia. Electrocardiographic changes included junctional rhythm, incomplete right bundle branch block and ST and T waves abnormalities, and ST segment elevation and first-degree atrioventricular block with intermittent complete heart block. In all cases, biopsy or resection of the lesion or cytologic examination of the pericardial fluid established a diagnosis. All tumors were of B-cell phenotype and included 4 cases of large cell lymphoma and one unclassifiable small cell lymphoma. In 2 cases, a follicular center cell origin was supported by reactivity of the neoplastic cells for CD10 and bcl-6 and by bcl-2 gene rearrangement by molecular analysis. One patient died shortly after diagnosis due to cerebral infarction. Two patients are alive without disease after chemotherapy with CHOP after 120 and 192 months. One patient underwent chemotherapy with CHOP and rituximab, and shows persistent cardiac involvement by lymphoma but with a decrease in tumor burden at 7 months of follow-up. One patient was lost to follow-up. Clinical outcome is variable; however, early diagnosis in conjunction with effective treatment (surgery and/or chemotherapy) may result in an excellent prognosis. Primary cardiac lymphoma should be included in the differential diagnosis of a right atrial mass. PMID- 17721190 TI - The role of P501S and PSA in the diagnosis of metastatic adenocarcinoma of the prostate. AB - BACKGROUND: Adenocarcinoma of the prostate can present as metastatic carcinoma with no known primary. Prostatic origin can be confirmed in most of these cases by immunohistochemistry for prostate-specific antigen (PSA) and prostate-specific acid phosphatase. In a small subset of high-grade prostate carcinomas, both markers are negative and therefore are not helpful for confirming prostatic origin. Recently, novel marker proteins that are preferentially expressed in prostate tissue were identified. One such marker is P501S or prostein, a 553 amino acid protein that is localized to the Golgi complex. It is expressed in both benign and neoplastic prostate tissues, but not in any other normal or malignant tissue examined to date. Owing to its apparent specificity, prostein may be a good marker to demonstrate prostatic origin in metastatic prostate cancer. DESIGN: Five-micron sections of a tissue microarray were subjected to immunohistochemistry with a monoclonal mouse anti-P501S (clone 10E3, Dako, Carpintera, CA) antibody and a monoclonal mouse anti-PSA (clone ER-PR8, Dako, Carpintera, CA) antibody. The tissue microarray contains 78 cases of metastatic prostatic adenocarcinoma, 20 cases of primary prostatic adenocarcinoma, and 20 cases of benign prostate tissue from the peripheral zone as well as samples of benign brain, pancreas, kidney, thyroid, testis, skeletal muscle, and fibroconnective tissue. RESULTS: Similar staining (intensity and extent) was identified for both markers in the majority of metastatic tumors (11 distant sites, 42 pelvic lymph nodes), in all 20 primary tumors and in all benign prostate and nonprostate tissues. The P501S stain had perinuclear cytoplasmic (Golgi) distribution even in poorly differentiated tumors and metastases. Two distant metastases were negative for PSA but retained focal weak positivity for P501S. Two other distant metastases were weakly PSA positive, but strongly P501S positive. Metastases in the pelvic lymph nodes were positive for both markers in 53 cases and 1 lymph node metastasis was strongly PSA positive but P501S negative. In summary, 67 of the 69 cases (97%) of metastatic prostate carcinomas were PSA positive, whereas 68 of the 69 cases showed at least focal weak reactivity for P501S (99%). None of the tumors were negative for both markers. CONCLUSIONS: Immunohistochemistry for P501S is a sensitive and highly specific marker for identifying prostate tissue. The large majority of metastatic prostatic adenocarcinomas are P501S positive (99%). A small subset of metastatic prostatic adenocarcinoma shows significant differences in staining intensity and extent for PSA and P501S and, therefore, combined use of these markers may result in increased sensitivity for detecting prostatic origin. PMID- 17721191 TI - Germ cell tumors with sarcomatous components: a clinicopathologic and immunohistochemical study of 46 cases. AB - The clinicopathologic features of 46 patients with germ cell tumors with sarcomatous components (GCTSC) involving either the primary site or their metastases were studied. There were 43 men and 3 women aged 17 to 74 years. Twenty-three tumors arose in the mediastinum, 2 in the retroperitoneum, and 21 in the gonads. The germ cell component consisted of pure mature or immature teratoma (23 cases), teratoma mixed with other seminomatous or nonseminomatous components (17), pure seminoma (2), intratubular germ cell neoplasia (1), and yolk sac tumor (1). The SC included embryonal rhabdomyosarcoma (29), angiosarcoma (6), leiomyosarcoma (4), undifferentiated sarcoma (3), myxoid liposarcoma (1), malignant peripheral nerve sheath tumor (1), malignant "triton" tumor (1), and epithelioid hemangioendothelioma (1). Immunohistochemical studies were carried out in 34 cases with appropriate results supporting the diagnoses. Metastases containing both GCT and SC were observed in 6 cases, metastases of SC alone in 4, and metastases containing only GCT elements in 3. All patients were treated by cisplatinum-based chemotherapy plus other agents followed by surgery. Clinical follow-up was available in 40 patients (1 to 96 mo; mean=24 mo). Thirty-two of 40 patients either died of tumor (25/40; 62.5%) or were alive with advanced, progressive disease (7/40; 17.5%), and only 8/40 (20%) were alive and free of disease between 5 to 40 months (mean=18 mo). Comparison of these patients with an age-matched and stage-matched control group of patients with GCT without SC showed statistically significant differences in survival between the 2 cohorts (P 50% of positive cells) in all positive cases. When positive in the non-Sertoli cell tumors, the extent of expression tended to be focal to patchy (50% or less positive cells). In Sertoli cell tumors, inhibin and calretinin were expressed in 96% and 54% of cases, respectively. The extent of expression of inhibin tended to be diffuse, similar to WT1; however, the extent of immunostaining for calretinin tended to be focal to patchy. The immunohistochemical composite scores for WT1, inhibin, and calretinin were 11.2, 7.6, and 4.8, respectively. Coordinate patterns for the extent of expression of WT1, inhibin, and calretinin in pure Sertoli cell tumor showed that all 3 markers were positive in 54% of cases; however, 42% were positive for WT1 and inhibin but negative for calretinin. In cases positive for both WT1 and inhibin, expression of both markers was diffuse in 84% of cases, but WT1 was diffuse while inhibin was focal to patchy in 16% of cases. We conclude that ovarian Sertoli cell tumor should be added to the growing list of WT1-positive tumors. This marker is useful for the distinction of Sertoli cell tumor from endometrioid tumors and carcinoid. The diagnostic utility of WT1 in Sertoli cell tumor is similar to inhibin but better than that of calretinin. PMID- 17721195 TI - Translocation-positive low-grade fibromyxoid sarcoma: clinicopathologic and molecular analysis of a series expanding the morphologic spectrum and suggesting potential relationship to sclerosing epithelioid fibrosarcoma: a study from the French Sarcoma Group. AB - Low-grade fibromyxoid sarcomas (LGFMS) bear either the t(7,16) (q32-34;p11) or t(11,16) (p11;p11) translocations, resulting in FUS-CREB3L2 or FUS-CREB3L1 fusions, respectively. Heretofore, fusion transcripts were mainly detected in frozen tissues, using reverse transcription-polymerase chain reaction. In this study, we aimed to develop a reliable method to detect these in paraffin-embedded tissues, and to examine the clinicopathologic characteristics of a series of translocation-positive LGFMS. Sixty-three neoplasms with typical morphologic features of LGFMS and 66 non-LGFMS tumors selected for their resemblance to LGFMS (LGFMS-like tumors) were examined. RNA of sufficient quality could be extracted from 111/129 (86%) cases (59 LGFMS, 52 non-LGFMS). Of all, 48/59 (sensitivity, 81%) LGFMS contained detectable transcripts (45 FUS-CREB3L2, 3 FUS-CREB3L1). Most relevant clinicopathologic features of fusion-positive LGFMS included predominance in lower extremities (22/48; thigh: 13/48), deep situation (46/48), and occasional presence of unusual histologic features, for example, hypercellular areas (16/48), foci of epithelioid cells (13/48), and giant rosettes (6/48). Most tumors expressed EMA (41/45), at least focally, CD99 (38/41) and bcl-2 (36/41) while being essentially negative for CD34 (2/45), mdm2 (1/41), smooth muscle actin (1/45), S100 protein (0/46), desmin (0/44), h caldesmon (0/42), keratins (0/44), and CD117 (0/40). Eleven presumed LGFMS were fusion negative. Of all, 7/52 non-LGMFS neoplasms contained FUS-CREB3L2 transcripts, of which 4 had been diagnosed as sclerosing epithelioid fibrosarcoma. In conclusion, FUS-CREB3L1/L2 fusion transcripts can be detected in paraffin-embedded LGFMS in a sensitive manner, using reverse transcription polymerase chain reaction. Most fusion-positive LGFMS are EMA-positive and CD34/S100/smooth muscle actin negative. The presence of epithelioid cells and fusion transcripts in both LGFMS and a subset of sclerosing epithelioid fibrosarcoma suggest that these neoplasms might be related. PMID- 17721196 TI - Epstein-Barr virus hepatitis: diagnostic value of in situ hybridization, polymerase chain reaction, and immunohistochemistry on liver biopsy from immunocompetent patients. AB - Epstein-Barr virus (EBV) hepatitis is an uncommon, almost always self-limited disease in immunocompetent patients. Accurate diagnosis is imperative for appropriate clinical management. The aim of this study was to compare 3 available methods for EBV detection on routinely processed liver biopsies to determine their effectiveness in aiding the diagnosis. In 6 of the 8 cases of EBV hepatitis, EBV was detected by both polymerase chain reaction (PCR) for EBV DNA and in situ hybridization (ISH) for EBV early RNA (EBER). EBV was detected by PCR only in 1 case, and by ISH only in another. EBER-positive cells detected by ISH were typically few and individually distributed in the portal tracts and sinusoids. Immunohistochemical staining for EBV latent membrane proteins was negative in all 8 cases. Five cases of chronic hepatitis C used as negative controls were negative by all 3 detection methods for EBV. These data indicate that PCR and ISH are equally sensitive in detecting EBV in routinely processed liver biopsies. The ready implementation of ISH in pathology laboratories makes it a useful ancillary tool in confirming the diagnosis of EBV hepatitis in equivocal cases. However, EBER-positive cells can be sparse and easily overlooked. Immunohistochemistry for EBV latent membrane proteins apparently has no utility in the diagnosis of EBV hepatitis. PMID- 17721197 TI - Bile duct dysplasia in the setting of chronic hepatitis C and alcohol cirrhosis. AB - Intrahepatic cholangiocarcinomas are rare and risk factors remain incompletely understood, but one recently identified potential risk factor is chronic hepatitis C (HCV) infection. To further study this potential association, we searched for dysplasia in the intrahepatic bile ducts in native explanted livers in cases of chronic HCV and control groups. Cases of chronic biliary tract disease were excluded. A total of 1058 explants were reviewed: HCV (511), alcohol alone (112), HCV and alcohol (85), HBV (67), cirrhosis from other causes (149), and noncirrhotic livers, for example, cases transplanted for acute liver failure (134). Dysplasia of the intrahepatic bile ducts was seen in 19/1058 (1.8%) of cases and was associated with chronic HCV infection and alcohol use, P=0.01. Ten out of 19 cases of dysplasia were in the setting of chronic HCV, 5/19 were in the setting of alcohol alone, and the remaining 4/19 were in the setting of combined HCV and alcohol. Seventeen out of 19 cases were classified as low-grade dysplasia and 2/19 as high-grade dysplasia. In all cases of dysplasia, the lesions were multifocal and involved septal-sized bile ducts. In 16/19 cases, the dysplasia was papillary whereas in 3/19 cases the dysplasia was flat. In conclusion, dysplasia can be found within the intrahepatic bile ducts in chronic HCV cirrhosis, supporting recent epidemiologic studies identifying chronic HCV as a major risk factor for intrahepatic cholangiocarcinoma. Alcohol also seems to be a risk factor. The dysplastic changes are multifocal, involve septal sized bile ducts, and are typically papillary. PMID- 17721199 TI - Further characterization of the muscle layers and lamina propria of the urinary bladder by systematic histologic mapping: implications for pathologic staging of invasive urothelial carcinoma. AB - The muscularis mucosae (MM) and muscularis propria (MP) are important landmarks for pathologic tumor (pT) staging of urinary bladder cancer, which is the quintessential prognostic factor. In our routine practice, we have occasionally noted patterns of MM, which do not always conform to the originally described configuration of thin slender bundles arranged in a single layer of interrupted, dispersed, or continuous muscle. We evaluated the lamina propria (LP), MM, and MP characteristics in 35 urinary bladder resection specimens with systematic sampling from the dome, trigone, anterior, posterior, right, and left lateral walls. Among the subsites, the trigone had a relatively flatter surface and attenuated LP depth (0.46 to 1.58 mm), about half of the thickest region which was the dome (0.98 to 3.07 mm). The MM was typically in individual or small groups of slender and wavy fascicles or wispy fibers. MM also had focal to rarely extensive hyperplastic appearance (53%, most common in dome) with 2 recognizable patterns: (a) aggregates of hyperplastic MM with haphazard outlines (33%) distinct from that of MP, and (b) hyperplastic compact MM with parallel muscle fibers and regular outline arranged singly or in small groups (45%) that occasionally strongly resembled MP muscle but distinguishable from it on the basis of the location in the LP. By distribution, these muscle bundles were more typically dispersed or formed a discernable layer (41%) as discontinuous or infrequently near-continuous layer. The LP vascular plexus was present in every section most often in association with the MM muscle; however, variations in the distribution were observed. The MP most commonly had a relatively regular interface with the LP. A distinctive pattern was noted in the trigone where occasionally there was gradual diminution of size of the MP muscle bundles as they extended to almost a suburothelial location. In 22%, isolated or small groups of compact regular hyperplastic MM muscle bundles were noted in deep LP situated between the more typical slender MM layer and the MP. In conclusion, there are additional patterns of MM other than previously described. Awareness of the occasionally hyperplastic appearance of MM muscle is important to prevent overstaging of invasive urothelial carcinoma. In transurethral resection specimens, lack of orientation may preclude distinction of the hyperplastic MM from true MP in these rare situations. The number and orientation of muscle bundles, relationship to urothelium and vascular plexus, and comparison with more characteristic MP, if present, would be helpful; isolated bundles immediately adjacent to the urothelium with loose haphazard fiber orientation and irregular outlines favor MM over MP muscle. The hyperplastic MM mimicking MP may be more challenging; isolated muscle bundles immediately adjacent to the urothelium would favor hyperplastic pattern of MM over MP muscle. Topographical variations exist among the subsites, the more superficial location of the MP and the rarity of MM in the trigone, relative abundance of hyperplastic MM in dome, and presence of the more superficial ureteral MP at its insertion in the bladder complicate the traditional pT stage evaluation of invasion in these regions. The inconsistency of a distinct MM layer and variations in the LP vascular plexus indicate that substaging of pT1 would be problematic and thus provides further support to the World Health Organization/International Society of Urological Pathology 1998 and World Health Organization 2004 recommendation against its implementation at the current time. PMID- 17721198 TI - Squamous cell carcinoma in situ of the breast: a light microscopic and immunohistochemical study of a previously undescribed lesion. AB - Three cases of squamous carcinoma in situ of the breast, one with an invasive component are described in women aged 35, 51, and 59 years. Two cases were detected by screening mammography. In 1 case, the squamous ductal carcinoma in situ was extensive. All cases showed obvious squamous features on standard hematoxylin and eosin sections. The in situ component of the lesions and the squamous differentiation were supported by immunohistochemistry. In 2 cases, the neoplastic cells showed actin positivity indicating myoepithelial cell differentiation. One case showed trilineage differentiation into luminal, squamous, and myoepithelial cells. These cases illustrate a variant of duct carcinoma in situ that has not been described in the current literature and provide insights into the dual epithelial-myoepithelial differentiation of some breast neoplasms. PMID- 17721200 TI - The spectrum of histopathologic and immunohistochemical findings in folliculotropic mycosis fungoides. AB - BACKGROUND: Since the original designation of folliculotropic mycosis fungoides (FMF) as a distinct entity, there has been an increasing appreciation of the broad clinical and histopathologic spectrum with which this disease can present. However, there have been few large histologic studies characterizing the various histopathologic patterns. OBJECTIVE: In this study, we attempt to describe the histopathologic and immunohistochemical features of 47 biopsy specimens from 34 patients with FMF. METHODS: We searched our lymphoma database for patients with FMF in which detailed histopathologic information and slides as well as clinical information was available for review. Additionally, immunohistochemical studies for CD4, CD8, and CD1a were performed in all cases in which the block was available. RESULTS: In addition to the prototypical pattern of a folliculotropic lypmphoid infiltrate with or without mucinosis, the histologic features of follicular mycosis fungoides may include a granulomatous reaction, cystic and comedonal changes, an eosinophilic folliculitis pattern and basaloid folliculolymphoid hyperplasia as well as pustular changes, interface dermatitis and an interstitial dermatitislike pattern. Unlike conventional mycosis fungoides, eosinophils and plasma cells are conspicuous within the accompanying reactive infiltrate. We have also noted an exceedingly high number of Langerhans cells within the follicular epithelium. The CD4:CD8 ratio frequently is 10:1 or greater and the follicles show abundant CD1a positive cells. CONCLUSIONS: FMF may present with a broad spectrum of histopathologic changes including interstitial, granulomatous, fibrotic and acneiform reactions that may lack the typical histologic attributes of a cutaneous T-cell lymphoma. Recognition of these myriad of histologic presentations can be of great diagnostic utility. PMID- 17721201 TI - HHV-8+, EBV+ multicentric plasmablastic microlymphoma in an HIV+ Man: the spectrum of HHV-8+ lymphoproliferative disorders expands. AB - Human herpesvirus-8 (HHV-8) is associated with several distinct lymphoproliferative disorders: primary effusion lymphoma, multicentric Castleman disease (MCD), MCD-associated plasmablastic lymphoma and HHV-8+, Epstein-Barr virus (EBV)+ germinotropic lymphoproliferative disorder. We report the case of a human immunodeficiency virus (HIV)+ male with fever, generalized lymphadenopathy, and splenomegaly. Two peripheral lymph nodes were excised and showed features of MCD and a prominent proliferation of HHV-8+, EBV+, CD20, CD138, MUM1+, lambda dim+, Ig heavy chain plasmablasts and immunoblasts replacing some follicles. Subsequently, a splenectomy and biopsy of retroperitoneal lymph nodes were performed; the retroperitoneal and splenic hilar lymph nodes showed changes similar to those in the peripheral lymph nodes while the markedly enlarged spleen showed replacement of occasional white pulp by the HHV-8+, EBV+ large cells. The histologic features and coinfection by EBV and HHV-8 suggested a diagnosis of HHV 8+ germinotropic lymphoproliferative disorder. However, the occurrence in an HIV+ individual, the background of MCD, the widespread anatomic distribution and the aggressive clinical course tended to exclude germinotropic lymphoproliferative disorder, and to favor multifocal plasmablastic microlymphoma. The patient died shortly after surgery; postmortem examination showed progression to overt lymphoma. The marrow showed extensive hemophagocytosis, consistent with development of a hemophagocytic syndrome. This unique case has clinical features compatible with a MCD-associated plasmablastic lymphoproliferative disorder, with pathologic features intermediate between HHV-8+ plasmablastic microlymphoma, and HHV-8+ germinotropic lymphoproliferative disorder, although in contrast to both of these, in our case, light chain expression was dim and heavy chain was not detected. PMID- 17721202 TI - Epstein-Barr virus gastritis: an underrecognized form of severe gastritis simulating gastric lymphoma. AB - We describe an exceedingly rare case of severe gastritis that was temporally associated with primary Epstein-Barr virus (EBV) infection. The patient was a 59 year-old immunocompetent man who presented with intermittent fever of unknown origin and epigastric pain for 18 days. A computed tomographic scan of the abdomen showed diffuse thickening of the gastric wall and esophagogastroduodenoscopy revealed numerous ulcers in the stomach. Histologic examination of gastric biopsies showed a dense and diffuse atypical lymphoid infiltrate in the lamina propria with erosions and focal lymphoepithelial lesions. No lymphoid follicles or Helicobacter microorganisms were identified. Immunohistochemical studies demonstrated the lymphoid infiltrate to consist of mixed T and B cells. Immunoglobulin heavy chain gene arrangement analysis showed a polyclonal pattern. The plasma cells present in the biopsies exhibited no light chain restriction as determined by in situ hybridization. Concurrent clinical work-up revealed peripheral lymphocytosis with atypical lymphocytes and positive serum IgM antibody to EBV capsid antigen in the absence of IgG antibody. These findings indicated that the gastric abnormalities were related to primary EBV infection as the predominant manifestation of infectious mononucleosis. This was further confirmed by subsequent in situ hybridization showing numerous EBV positive lymphocytes in the gastric mucosa. The patient's symptoms were spontaneously resolved with only supportive treatment. A follow-up endoscopy 2 months later showed completely normal gastric mucosa and he remained well with no gastrointestinal complaints for 2 and a half years. This case illustrates the importance of a high index of suspicion to avoid misdiagnosis of gastric lymphoma that requires more aggressive therapies. PMID- 17721204 TI - Comment on the Article: Srodon M, Stoler MH, Baber GB, et al. The distribution of low and high-risk HPV types in vulvar and vaginal intraepithelial neoplasia (VIN and VaIN) Am J Surg Pathol. 2006;30:1513-1518. PMID- 17721205 TI - Perivascular Epithelioid Cell Tumors (PEComas) and Smooth Muscle Tumors of the Uterus. PMID- 17721207 TI - Management algorithm and outcome evaluation of partial mastectomy defects treated using reduction or mastopexy techniques. AB - BACKGROUND: Reconstruction of the partial mastectomy defect has become increasingly popular because of poor cosmetic results in select patients. The purpose of this series was to try to create a treatment algorithm based on patient selection, diagnosis, margins, and recurrence in an attempt to maintain oncologic safety, as well as to improve esthetic outcome. METHODS: A retrospective review of all patients treated at Emory University Hospital with partial mastectomy and reduction/mastopexy was performed. Reconstruction was performed either simultaneously or following confirmation of negative histologic margins. RESULTS: Sixty-three women were included in the series. Histology was invasive carcinoma (n = 33), ductal carcinoma in situ (DCIS) (n = 20), fibroadenoma (n = 6), and benign breast tissue (n = 4). The Wise pattern was used 84% of the time (n = 53/63). The most common tumor location was upper outer quadrant, and the various pedicles used were superomedial (n = 22), inferior (n = 20), central (n = 7), and other (n = 14). Eight patients had reduction/mastopexy once final pathology confirmed negative margins. The average biopsy weight was 236 g. Total specimen weight on the tumor side was 762 g and 858 g on the contralateral side, to accommodate for radiation fibrosis. Immediate complications were seen in 22% of cases and included delayed healing (n = 9), infection (n = 1), partial nipple loss (n = 1), hematoma (n = 1), and skin necrosis (n = 1). In patients with breast cancer (n = 53), 26% required either fine needle aspiration or excisional biopsy for cancer surveillance postoperatively. Oncoplastic surgery was the definitive procedure 93% of the time. Completion mastectomy with reconstruction was required in 4 patients, 3 for positive margins extensive DCIS and 1 for residual microcalcifications (stereobiopsy DCIS) despite adequate specimen radiograph and negative margins initially. All 4 patients who failed the combined approach were younger women with the diagnosis of extensive DCIS. The locoregional recurrence rate was 2%, and all patients had no evidence of disease at an average follow-up of 3.25 years. CONCLUSION: Therapeutic mammaplasty is a useful procedure for shape and symmetry preservation in women with large or ptotic breasts. Versatility exists using various pedicles and skin patterns to reconstruct all breast shapes and defect locations. Younger patients with extensive DCIS are poor candidates for simultaneous reconstruction, and should be deferred until confirmation of negative margins. If surgical management of residual disease requires completion mastectomy, immediate reconstruction is possible, with skin preservation and no adverse effects. PMID- 17721208 TI - Transumbilical breast augmentation: a practical review of a growing technique. AB - BACKGROUND: The transumbilical breast augmentation procedure has been described in the literature since 1993. This indirect route for implant placement has received both criticism and praise over the years, without a comprehensive assessment of the procedure from the perspective of the patient. The growing patient demand for the procedure, combined with the increased use by surgeons, prompts a review of the procedure and a discussion of its pros and cons, including tabulated patient satisfaction data. METHODS: A retrospective chart review of 245 transumbilical breast augmentations performed by the second author from 2002 to 2004, including the 1-year patient satisfaction surveys, is presented. Additionally, complications from the procedure are also tabulated and compared with the complications published by our studies' dominant implant manufacturer in their 1-year follow-up published data. The patients were asked to rate their postoperative pain, numbness, firmness, size satisfaction, rippling, and overall satisfaction. Data were compiled and statistical analysis was performed using chi methods. RESULTS: The study revealed a strong negative correlation between both the study parameters of prepectoral implant location and postoperative firmness and the survey result of overall satisfaction (P = 0.0041). Conversely, numbness, pain, and rippling, long felt to be linked to satisfaction, were shown to have no statistical correlation with satisfaction. A strong positive correlation with satisfaction was seen with retropectoral (submuscular) implant location. The complications from transumbilical breast augmentation in our study were hematoma = 1 (0.4%), umbilical wound infection = 8 (3.2%), deflation = 3 (1.2%), tunnel seromas = 5 (2.0%), asymmetry = 10 (4.1%), capsular contracture = 9 (3.7%), implant infection (0.0%). These complication rates were comparable or less than other published methods of breast prosthesis implantation. CONCLUSIONS: Transumbilical breast augmentation is a safe and effective method for breast implant placement in selected patients. Patient satisfaction weighs heavily on implant location and postoperative firmness and less on other variables. The procedure is associated with a complication rate comparable with other methods and finds itself growing in demand and popularity secondary to high patient satisfaction. PMID- 17721209 TI - Inferolateral AlloDerm hammock for implant coverage in breast reconstruction. AB - PURPOSE: Implant reconstruction is commonly performed to reconstruct mastectomy defects or to correct breast hypoplasia. We have been using an inferolateral AlloDerm hammock as an inferior extension of the pectoralis major muscle to provide a mechanical barrier between the implant and skin and to control implant position. METHODS: The inferior border of the AlloDerm hammock is attached inferiorly to the rectus abdominis fascia and laterally to the serratus anterior fascia to create the borders of the implant pocket. The AlloDerm is then sewn to the pectoralis major muscle to enclose the implant. RESULTS: The AlloDerm hammock was used in 43 patients and 67 breasts for immediate expander-implant reconstruction (10), immediate silicone implant reconstruction (30), delayed expander-implant reconstruction (4), and revisional implant reconstruction for capsular contracture following capsulectomy (23). The AlloDerm hammock allowed complete coverage of the implant and symmetric positioning of the inframammary fold. In delayed reconstructions with existing skin redundancy at the mastectomy site, inferior epigastric tissue was recruited and tissue expanders filled over 75% of the desired volume, thus decreasing the need for subsequent filling. Patients were overall satisfied with their results and had few complications. No capsular contracture, hematoma, or seroma was observed in 6 months to 3 years of follow-up. CONCLUSION: Implant reconstruction with an inferolateral AlloDerm hammock facilitates positioning of the implant in immediate or revisional breast reconstruction and simplifies expander-implant reconstruction. This safe technique is easy to learn and should be considered a viable option for breast reconstruction. PMID- 17721210 TI - Comparison of fat necrosis between zone II and zone III in pedicled transverse rectus abdominis musculocutaneous flaps: a prospective study of 400 consecutive cases. AB - Fat necrosis in transverse rectus abdominis musculocutaneous (TRAM) flap is considered to be mainly affected by blood supply. This prospective study compares the incidence of fat necrosis between zones II and III in 400 consecutive patients who had undergone unipedicled TRAM flap breast reconstruction. Fifty eight patients (14.5%) suffered from fat necrosis, and 7 had 2 separate nodules. Fifty-four occurred in zone II, 10 in zone III, and 1 in zone I. The incidence of fat necrosis in zone II was significantly higher than in zone III (P < 0.001). The weight of the mastectomy specimen and the relative amount of zone II tissue included in the flap had positive correlation with the incidence of fat necrosis. This result implies relatively poor perfusion of zone II compared with zone III. PMID- 17721211 TI - The triple-flap nipple-reduction technique. AB - BACKGROUND: Pure nipple hypertrophy (macrothelia) is a known but rare condition. Nevertheless, minor disproportions between nipple diameter or height and the areola are quite common. During breast surgery, the surgeon often faces the patient's wish to perform nipple reduction. However the methods described are difficult or have drawbacks. This article proposes a simple technique for both height and diameter, or height only, nipple reduction. METHOD: A technique consisting of the creation of 3 symmetrical triangular flaps in a "Y" fashion and excision of the core of the nipple was performed on 15 consecutive patients between 2001 and 2004. The esthetic results, scars, sensibility, erectility, and complications were evaluated. RESULTS: All patients presented good to excellent esthetic results, with inconspicuous scars. No major complications occurred in this series. Erectility function of the nipple was preserved in all 15 patients, which is a significant difference when compared with previously published techniques. Alterations in sensibility were temporary and were comparable with summarized alterations in representative published clinical series of both breast reduction and augmentation. CONCLUSION: The triple-flap nipple-reduction technique has the advantage of feasibility, applicable in both height and diameter nipple hypertrophy, with excellent esthetic results and the preservation of both sensibility and erectility. PMID- 17721212 TI - Bipolar coagulation-assisted orbital (BICO) septoblepharoplasty: a retrospective analysis of a new fat-saving upper-eyelid blepharoplasty technique. AB - BACKGROUND: Upper eyelid blepharoplasty generally is performed as a combination of excess skin reduction and fat resection. Fat resection can in the long term result in a hollow orbit. Therefore, treatment of the lax orbital septum, in combination with skin reduction, seems a more preferable approach than fat resection. The authors describe a technique of upper-eyelid blepharoplasty: a combination of excess skin reduction and shortening of the stretched lax orbital septum by means of bipolar coagulation. This procedure is called bipolar coagulation-assisted orbital septoblepharoplasty, ie, BICO septoblepharoplasty. The aim of this retrospective study is to report on our initial experience with this technique. METHODS: We retrospectively analyzed 296 patients in whom an upper-eyelid blepharoplasty was performed during the past 4 years using the BICO septoblepharoplasty technique: first, excess skin is removed, then a small rim of orbicularis muscle is excised to expose the bulging orbital septum, and finally, before closure of the wound, bipolar coagulation of the exposed orbital septum is performed. This results in shrinkage of the septum and thus in repositioning of the pseudoherniated fat pads. RESULTS: At discharge from follow-up, which varied from 9 weeks (72% of the patients) up till 2 years after surgery (28% of the patients), in all patients ultimately a satisfactory result was achieved and ultimately all were satisfied or very satisfied with the result of the procedure. There were only 3 patients with minor complications: 1 patient with a slightly retracting scar, which resolved spontaneously, and 2 patients with slight asymmetry requiring additional skin resection. CONCLUSIONS: BICO septoblepharoplasty of the upper eyelid seems to be an effective way to treat blepharochalasia of the upper eyelid; the bipolar coagulation of the orbital septum will lead to shrinkage of the septum, thereby repositioning the prolapsing medial and central fat pads. Secondary fibrosis will reinforce the orbital septum postoperatively. PMID- 17721213 TI - Septocolumellar suture in closed rhinoplasty. AB - Several surgeons advise a variety of tip sutures and describe their own techniques in open approach. Septocolumellar suture is one of them and can be described as a loop suture between the medial crura and caudal septum. Although some of the articles mention that it can be applied in closed rhinoplasty, there is no description of the technical details. This paper presents indications, technical steps, and advantages of the septocolumellar suture in closed rhinoplasty. After completing the classic sequence of the endonasal extramucous technique, the medial crural cartilages are dissected from the overlying skin at the midcolumellar level, keeping the distal fibrous attachments between the anterior columellar skin and these cartilages intact. A 5/0 or 4/0 Prolene (Ethicon Ltd, UK) with a round needle is passed, penetrating both the medial crura and then the caudal septum. Depending on the penetration level of this suture, the tip projection can be increased or decreased, the tip can be rotated, and columellar show can be corrected. This suture also makes the medial crura of the alar cartilages and septum rigidly fixed together, thus providing stability. Depending on the experience gained in 433 primary and 62 secondary rhinoplasty cases since 2000, it can be claimed that this technique, presenting an alternative to the open approach in many cases and expanding the borders of closed approach, allows one to manipulate the tip and columella easily with closed rhinoplasty and provides a significant decrease in the suboptimal results and number of complications. PMID- 17721214 TI - A new method for the correction of small pixie earlobe deformities. AB - A fair number of patients show pixie earlobe deformities in East Asia. Some of them also show small earlobes. They request their earlobes enlarged, in addition to the correction of the pixie earlobe deformities. In this article, I propose a new method for the simultaneous correction of the pixie earlobe and the small earlobe deformities. The pixie earlobe deformities were corrected by an upward lifting of a V-shaped flap. The earlobe expansion was performed using autogenous conchal cartilage and dermafat harvested from the paracoccygeal region. The method provides not only mediolateral expansion of the earlobe but also marginal expansion. Between 2002 and 2005, both ears of 6 patients were corrected using this method. The final esthetic results were gratifying to the patients, as well as to the surgeon. PMID- 17721216 TI - Comparison of the postoperative outcome in pure medial orbital fracture among three groups: using porous polyethylene or hydroxyapatite through subciliary approach and transnasal endoscopic correction. AB - Many methods of surgical repair of pure medial orbital fractures have been reported. In this study, we discuss the outcome from the surgical corrections of hydroxyapatite (Biocoral) or porous polyethylene (Medpor) through subciliary approach, and the transnasal endoscopic corrections. Between March 1993 and July 2003, 63 patients were treated with porous polyethylene and 48 patients were treated with hydroxyapatite. Between August 2003 and December 2005, 50 patients were treated with transnasal endoscopic approach. Patients had at least 6 months' follow-up, and the records for diplopia, enophthalmos, and other postoperative complications were reviewed retrospectively. As a result, 1 patient from the group using porous polyethylene, 2 patients from the group using hydroxyapatite, and 1 patient from the endoscopic correction group had enophthalmos. Besides enophthalmos, no other complications were observed. There was no significant statistical correlation among 3 groups. In conclusion, a transnasal endoscopic correction may be considered a useful method for surgical repair of pure medial orbital fractures, with no external facial scar and excellent visualization and accuracy comparable to that of the subciliary approach. PMID- 17721215 TI - A new method in the treatment of ear amputation: experimental and clinical study. AB - There have been plenty of reconstruction methods for ear amputation, and replantation preserves its importance. In situations where replantation is not feasible, various methods were proposed. We indicate an alternative technique for the ear amputation without replantation indication. The method of replacing of a vascular structure into the tunnel formed on the posterior side of the amputated ear was used instead of replacing the ear cartilage into a vascular area that was described in the literature of ear prefabrication. The dorsal fascial flaps which were prepared from the back of 10 New Zealand rabbits were placed into the amputated ear. The 2 groups, control and the experimental, were consequently the ear that was adapted as a composite graft and the ear with the flap inserted. The ears were examined macroscopically and photographed on postoperative days 3, 7, 14, and 21. On the 21st day, the nourishment pattern of the ear, the dorsal fascia, and the dorsal fascia adapted ear were investigated with digital subtraction angiography (DSA). The group that received applied dorsal fascia possessed increased vascularity. The viability was evaluated with the biopsies taken from the control group and the group that received applied dorsal fascial flap on the 21st day. The cartilage and the connective tissue were viable in the flap-applied group, whereas there was necrosis in the control group. The reflection of the experimental study was performed on 2 subtotal and 1 total ear amputation cases, with the utilization of the superficial temporal artery. The nourishment of the flaps was evaluated with postoperative photographs, angiography, and bone scintigraphy. PMID- 17721217 TI - Distally based posterior interosseous flap: primary role in soft-tissue reconstruction of the hand. AB - A series of 15 consecutive patients with various hand defects requiring flap coverage was reviewed in this study. The defects were all covered with the distally based posterior interosseous flap. Its main indications were in complex hand trauma, severe burn injury, or skin cancer ablation, either acute or postprimary. In 12 of the patients, flaps survived completely. In 3 patients, there was partial necrosis of the distal part of the flap, which did not require additional surgical procedure. Radial nerve palsy was noted in one of the cases, with a complete recovery after 3 months. Donor site was closed directly in up to 4-cm-wide flaps, while larger flaps required skin grafting. No major anatomic variation was observed. Distally based posterior interosseous flap is a reliable choice for various types and areas of hand defects, with very low donor-site morbidity, and should be more commonly considered in clinical practice. PMID- 17721218 TI - Contribution of a locking cross-stitch to a modified kessler core suture: a new technique. AB - We compared the gap-producing forces, ultimate tensile strength, and slip resistance of a new core suture technique and that of a modified Kessler suture in freshly harvested chicken tendons. Biomechanical trials were carried out using a tensile-strength testing machine. Our technique proved superior to the modified Kessler suture with respect to its ultimate tensile strength and slip resistance. PMID- 17721219 TI - A biomechanical analysis of distraction force in modified hynes-Giddins dynamic external fixator. AB - Hynes and Giddins modified the rubber band traction device advocated by Suzuki for management of phalangeal pilon fractures and fracture-dislocations. We present here a modification of the Hynes-Giddins version of this dynamic external fixator, which allows alteration of the distracting force by a simple adjustment of the construct. PMID- 17721220 TI - Zone of traction injury of the common peroneal nerve. AB - The history of functional motor recovery after reconstruction of traction injury to the common peroneal nerve is poor, regardless of technique and regardless of the experience of the surgeon doing the reconstruction. The hypothesis tested is that the failure of functional motor recovery after common peroneal nerve traction injury is because the zone of injury extends beyond the visible region of peroneal nerve in continuity injury and into the muscle entry zone of the motor nerve terminations. The opportunity arose to examine pathologically this suspected distal zone of injury in one patient. Histology from this patient was compared with that from a similar zone in a leg amputated for vascular indications. With a peroneal traction injury severe enough to cause disruption of the nerve, histology using Masson trichrome stain for collagen, neurofilament and S-100 stain for nerve fibers and Schwann cells demonstrated collagen deposition between the peroneal nerve and the muscle. This fibrosis was not seen in the in the same location from the amputation specimen. These findings were corroborated by electron microscopy of the myoneural junction in both specimens. It is concluded that stretch/traction injury zone extends into the myoneural junction, preventing otherwise successful neural regeneration through nerve grafts to reinnervate muscle. This suggests that with a distal zone of injury extending into the myoneural junction region, peroneal motor function may be better achieved by direct neurotization than with nerve grafting. PMID- 17721221 TI - The reverse sural artery fasciomusculocutaneous flap for small lower-limb defects: the use of the gastrocnemius muscle cuff as a plug for small bony defects following debridement of infected/necrotic bone. AB - The reverse sural artery fasciomusculocutaneous flap is a modification of the original fasciocutaneous flap in which a midline gastrocnemius muscle cuff around the buried sural pedicle is included in the flap. This modification was done to improve the blood supply of the distal part of the flap, which is harvested from the upper leg. The aim of this paper is to demonstrate that there is another important advantage of the modified flap: the use of the muscle cuff as a "plug" for small lower limb defects following debridement of infected/necrotic bone. A total of 10 male adult patients with small complex lower-limb defects with underlying bone pathology were treated with the modified flap using the muscle component to fill up the small bony defects. The bony pathology included necrotic exposed bone without evidence of osteomyelitis or wound infection (n = 1), an underlying neglected tibial fracture with wound infection (n = 4), and a sinus at the heel with underlying calcaneal osteomyelitis (n = 5). Primary wound healing of the flap into the defect was noted in all patients. No recurrence of calcaneal osteomyelitis was seen and all tibial fractures united following appropriate orthopedic fixation. It was concluded that the reverse sural artery fasciomusculocutaneous flap is well suited for small complex lower-limb defects with underlying bone pathology. PMID- 17721222 TI - A survey of microvascular protocols for lower-extremity free tissue transfer I: perioperative anticoagulation. AB - Reconstruction of the lower extremity using free tissue transfer is performed throughout the country by numerous surgical teams. However, no established protocol exists for the use of anticoagulation in the perioperative period. The present study sought to analyze trends in current protocols regarding perioperative anticoagulation for lower-extremity free flap reconstruction. Members of the American Society of Plastic Surgeons were surveyed with regard to their preferences for perioperative anticoagulation in conjunction with lower extremity free tissue transfer. The results demonstrated tremendous variability in both the agents used and therapeutic periods employed. They highlighted the absence of 1 or more common anticoagulation protocols and tried to establish common trends in the use of such agents. PMID- 17721223 TI - Effect of fresh and stored botulinum toxin a on muscle and nerve ultrastructure: an electron microscopic study. AB - The aim of this study was to compare the ultrastructural alterations of the muscle and nerve that appear following injection of freshly reconstituted and stored botulinum toxin A. Fifteen New Zealand white rabbits were assigned to 6 groups, and anterior auricular muscle was used for injections. Group 1 did not receive any injection and group 2 received saline injection. Groups 3 and 5 received fresh botulinum; muscles and motor nerves were harvested at 5 days and 12 weeks, respectively. Groups 4 and 6 received stored botulinum; muscles and motor nerves were harvested at 5 days and 12 weeks, respectively. Alterations in muscle and nerve ultrastructure were evaluated with electron microscopy. Degeneration findings in muscle after botulinum toxin injection revealed no significant difference between freshly reconstituted and stored toxin in the early period. When stored toxin was used, atrophic changes in the muscle were less severe than the fresh toxin at 3 months. On nerve evaluation, fresh toxin displays significant acute changes on nerve ultrastructure; however, fresh and stored toxin shows similar degeneration at 12 weeks. PMID- 17721224 TI - Roles of palatine bone denudation repairing with free buccal or palatal mucosal graft on maxillary growth: an experimental study in rabbits. AB - Most surgical repairs of cleft palate result in areas of bone denudation on lateral aspects of the hard palate. The present study was designed to investigate growth patterns of the maxilla following palatal bone denudation covering with free buccal or palatal mucosal graft in rabbits with surgically created defects simulating palatal bone denudation. Forty-five purebred New Zealand rabbits were used in this experiment. The animals were divided into 3 groups: 1 control group (left palatal bone denudation was not repaired and the right side was unoperated as a control) and 2 experimental groups (the right side of palatal bone denudation was covered with free buccal or palatal mucosal graft, respectively, and the left side was not repaired). Nineteen metric cranial variables were measured directly from the cleaned skulls. Direct cephalometric measurements were taken in the following dimensions: maxillary length, width and height, posterior facial width, and nasal deflection. Significant differences were noted between 2 sides of maxilla in all animals for the 19 cephalometric measurements. The cephalometric measurements of the right side in maxillary length, height, and width were significantly greater than those in the left side. There was no statistically significant difference between free buccal mucosal graft repaired group and free palatal mucosal graft repaired group for the cephalometric measurements. There was also no statistically significant difference for the cephalometric measurements between the 3 groups. The results of this study demonstrate that palatal bone denudation repaired by free buccal or palatal mucosal graft might prevent maxillary deformity following cleft palate surgery. PMID- 17721225 TI - Leptin increases extracellular matrix mineralization of human osteoblasts from heterotopic ossification and normal bone. AB - Heterotopic ossification (HO) is the pathologic formation of bone in soft tissue. The exact pathomechanism is unknown but probably involves a disturbed osteoblast differentiation. Leptin, known as the obesity gene, may regulate normal osteoblast function in vitro. The aim of the present in vitro study was to further analyze the pathomechanisms of HO, including a possible role of leptin in ectopic bone formation. Human osteoblasts were cultivated either from normal bone or from resected HO. Both groups were incubated with increasing doses of leptin. Phenotype expression and mineralization of extracellular matrix were measured after 7, 14, and 21 days. In both groups, leptin increased both the formation of bone nodules and Ca-45 incorporation. This is the first study to analyze the effect of leptin on bone cells from ectopic ossification. Similar to the in vitro behavior of normal osteoblasts, cells from HO respond to leptin exposure with an increased mineralization of the extracellular matrix. This mechanism may be involved in the pathogenesis of ectopic bone formation in vivo. PMID- 17721226 TI - Mandibular distraction for amniotic band syndrome in the neonate. AB - Prior reports have advocated the use of distraction osteogenesis (DO) in the management of neonates with mandibular hypoplasia to avoid early tracheostomy and its associated morbidity. Our center recently reported on the successful use of DO in a neonate with muscular dystrophy, a condition which affects the bone as well as the adjacent skeletal muscle. Herein, we describe the use of neonatal DO for mandibular hypoplasia in the setting of amniotic band sequence (ABS). The child had significant soft tissue contracture in the region of the cheek, associated with bilateral transverse facial clefts. This report highlights the successful utilization of DO for the treatment of mandibular hypoplasia and airway compromise in a patient with ABS. PMID- 17721227 TI - Successful treatment of hemophilic hand pseudotumors by only radiotherapy. AB - Hemophilic pseudotumor is a rare complication of hemophilia. We describe a 14 year-old young male with hemophilic pseudotumor in the second and fifth fingers of the left hand. We treated him only with radiotherapy. A total dose of 2000 cGy in 10 fractions was administered in 2 weeks. Factor VIII was not given. After 4 months, complete healing was seen. The patient was followed up at 24 months, and there was no evidence of recurrence and no bone growth disturbance. Based on our experience and a review of the literature, radiotherapy can be an effective alternative modality in treating hemophilic pseudotumor. PMID- 17721228 TI - Congenital duplication of the palm syndrome. AB - In this paper, we report a new case of congenital duplication of the palm syndrome (also known as limb/pelvis-hypoplasia/aplasia syndrome) and review previously reported cases and Wnt 7a gene mutations associated with that syndrome. Finally, we review the embryonic molecular events of limb development to explain the clinical features of the syndrome and to explain why the Swanson classification of duplication of the hand should be extended to include the dorsoventral duplication. PMID- 17721229 TI - Subungual melanoma: for a conservative approach on the thumb scale. AB - Melanoma management requires consideration of both oncologic and reconstructive principles to optimize both the likelihood of cure and quality of life. The plastic surgeon is encountering melanoma management that requires not only oncologic but also reconstructive surgery while considering both esthetic and functional results. Management of acrolentiginous melanoma typically involves the partial amputation of the thumb or the toe, with removal of the distal phalanx and the adjacent interphalangeal joint. The simple partial amputation of the second phalanx, preserving the pulp and the interphalangeal function (joints and tendinous insertions), and a made-to-measure ungual transfer provide excellent functional and esthetic results while maintaining similar oncologic outcomes. This report attempts to clarify the management of melanoma of the thumb. PMID- 17721230 TI - Correlation of high-resolution ultrasonographic findings with the clinical symptoms and electrodiagnostic data in carpal tunnel syndrome. PMID- 17721231 TI - Unreported complication of breast implants: inversion of port and detection with ultrasound. PMID- 17721232 TI - A new method for secure cannulation of blood vessels in experimental free flap surgery. PMID- 17721233 TI - An alternative to bolus tie-over dressing for full-thickness skin grafts for conchal cavity defects. PMID- 17721234 TI - Intraoperative repiercing for earlobe keloid. PMID- 17721235 TI - Microsurgical training: the chicken thigh model. PMID- 17721237 TI - Take it to the limit (one more time). PMID- 17721238 TI - Continuous local anesthetic wound infusion to improve postoperative outcome: back to the periphery? PMID- 17721239 TI - Glucocorticoids for acute and persistent postoperative neuropathic pain: what is the evidence? PMID- 17721240 TI - Influence of administration rate on propofol plasma-effect site equilibration. AB - BACKGROUND: The authors hypothesized a difference in plasma-effect site equilibration, depicted by a first-order constant k(e0), depending on the injection rate of propofol. METHODS: Sixty-one patients received 2.5 mg/kg propofol given as a bolus or as a 1-, 2-, or 3-min infusion. The Bispectral Index was used to monitor drug effect. Propofol predicted plasma concentration was calculated using a three-compartment model and the effect site concentration over time as the convolution between the predicted plasma concentration and the disposition function of the effect site concentration. The authors evaluated the influence of the infusion rate on the k(e0) by comparing the model with one k(e0) for all groups with models estimating different k(e0) values for each group. The authors also assessed the accuracy of two pharmacokinetic models after bolus injection. RESULTS: The best model based was a fixed (Bispectral Index > or = 90) plus sigmoidal model (Bispectral Index < 90) with two values of k(e0), one for the bolus (t(1/2) k(e0) = 1.2 min) and one for the infusions (t(1/2) k(e0) = 2.2 min). However, the tested pharmacokinetic models poorly predicted the arterial concentrations in the first minutes after bolus injection. Simulations showed the requirement for two k(e0) values for bolus and infusion was mostly a compensation for the inaccurate prediction of arterial concentrations after a bolus. CONCLUSION: Propofol plasma-effect site equilibration occurs more rapidly after a bolus than after rapid infusion, based on the electroencephalogram as a drug effect measure, mostly because of misspecification of the pharmacokinetic model in the first minutes after bolus. PMID- 17721241 TI - Median frequency revisited: an approach to improve a classic spectral electroencephalographic parameter for the separation of consciousness from unconsciousness. AB - BACKGROUND: In the past, several electroencephalographic parameters have been presented and discussed with regard to their reliability in discerning consciousness from unconsciousness. Some of them, such as the median frequency and spectral edge frequency, are based on classic spectral analysis, and it has been demonstrated that they are of limited capacity in differing consciousness and unconsciousness. METHODS: A generalized approach based on the Fourier transform is presented to improve the performance of electroencephalographic parameters with respect to the separation of consciousness from unconsciousness. Electroencephalographic data from two similar clinical studies (for parameter development and evaluation) in adult patients undergoing general anesthesia with sevoflurane or propofol are used. The study period was from induction of anesthesia until patients followed command after surgery and includes a reduction of the hypnotic agent after tracheal intubation until patients followed command. Prediction probability was calculated to assess the ability of the parameters to separate consciousness from unconsciousness. RESULTS: On the basis of the training set of 40 patients, a new spectral parameter called weighted spectral median frequency was designed, achieving a prediction probability of 0.82 on the basis of the "classic" electroencephalographic frequency range up to 30 Hz. Next, in the evaluation data set, the prediction probability was 0.79, which is higher than the prediction probability of median frequency (0.58) or spectral edge frequency (0.59) and the Bispectral Index (0.68) as calculated from the same data set. CONCLUSIONS: A more general approach of the design of spectral parameters leads to a new electroencephalographic spectral parameter that separates consciousness from unconsciousness significantly better than the Bispectral Index. PMID- 17721242 TI - Apolipoprotein E e4 allele increases the risk of early postoperative delirium in older patients undergoing noncardiac surgery. AB - BACKGROUND: Whether patients who subsequently develop early postoperative delirium have a genetic predisposition that renders them at risk for postoperative delirium has not been determined. METHODS: The authors conducted a nested cohort study to include patients aged > or = 65 yr who were scheduled to undergo major noncardiac surgery requiring anesthesia. A structured interview was conducted preoperatively and for the first 2 days postoperatively to determine the presence of delirium, defined using the Confusion Assessment Method. Blood was drawn for measurement of the apolipoprotein genotypes. Bivariate tests of association were conducted between delirium and apolipoprotein genotypes and other potentially important risk factors. Variables that had significant bivariate association with postoperative delirium were entered in a forward multivariable logistic regression model. RESULTS: Of the 190 patients studied, 15.3% developed delirium on both days 1 and 2 after surgery. Forty-six patients (24.2%) had at least one copy of the apolipoprotein e4 allele. The presence of one copy of the e4 allele was associated with an increased risk of early postoperative delirium (28.3% vs. 11.1%; P = 0.005). Even after adjusting for covariates, patients with one copy of the e4 allele were still more likely to have an increased risk of early postoperative delirium (odds ratio, 3.64; 95% confidence interval, 1.51-8.77) compared with those without the e4 allele. CONCLUSIONS: Apolipoprotein e4 carrier status was associated with an increased risk for early postoperative delirium after controlling for known demographic and clinical risk factors. These results suggest that genetic predisposition plays a role and may interact with anesthetic/surgical factors contributing to the development of early postoperative delirium. PMID- 17721243 TI - A conserved tyrosine in the beta2 subunit M4 segment is a determinant of gamma aminobutyric acid type A receptor sensitivity to propofol. AB - BACKGROUND: The gamma-aminobutyric acid type A receptor (GABAA-R) beta subunits are critical targets for the actions for several intravenous general anesthetics, but the precise nature of the anesthetic binding sites are unknown. In addition, little is known about the role the fourth transmembrane (M4) segment of the receptor plays in receptor function. The aim of this study was to better define the propofol binding site on the GABAA-R by conducting a tryptophan scan in the M4 segment of the beta2 subunit. METHODS: Seven tryptophan mutations were introduced into the C-terminal end of the M4 segment of the GABAA-R beta2 subunit. GABAA-R subunit complementary DNAs were transfected into human embryonic kidney 293 cells grown on glass coverslips. After transfection (36-72 h), coverslips were transferred to a perfusion chamber to assay receptor function. Cells were whole cell patch clamped and exposed to GABA, propofol, etomidate, and pregnenolone. Chemicals were delivered to the cells using two 10-channel infusion pumps and a rapid solution exchanger. RESULTS: All tryptophan mutations were well tolerated, and with one exception, all resulted in minimal changes in receptor activation by GABA. One mutation, beta2(Y444W), selectively suppressed the ability of propofol to enhance receptor function while retaining normal sensitivity to etomidate and pregnenolone. CONCLUSIONS: This is the first report of a mutation that selectively reduces propofol sensitivity without altering the action of etomidate. The reduction in propofol sensitivity is consistent with the loss of a hydrogen bond within the propofol binding site. These results also suggest a possible orientation of the propofol molecule within its binding site. PMID- 17721244 TI - Mechanical ventilation in healthy mice induces reversible pulmonary and systemic cytokine elevation with preserved alveolar integrity: an in vivo model using clinical relevant ventilation settings. AB - BACKGROUND: Mechanical ventilation (MV) may activate the innate immune system, causing the release of cytokines. The resulting proinflammatory state is a risk factor for ventilator-induced lung injury. Cytokine increase results from direct cellular injury but may also result from cyclic stretch alone as demonstrated in vitro: mechanotransduction. To study mechanotransduction in vivo, the authors used an animal MV model with clinically relevant ventilator settings, avoiding alveolar damage. METHODS: Healthy C57BL6 mice (n = 82) were ventilated (tidal volume, 8 ml/kg; positive end-expiratory pressure, 4 cm H2O; fraction of inspired oxygen, 0.4) for 30, 60, 120, and 240 min. Assigned animals were allowed to recover for 2 days after MV. Both pulmonary tissue and plasma interleukin (IL) 1alpha, IL-1beta, tumor necrosis factor alpha, IL-6, IL-10, and keratinocyte derived chemokine levels were measured. Histopathologic appearance of lung tissue was analyzed by light microscopy and electron microscopy. RESULTS: In lung tissue, all measured cytokines and keratinocyte-derived chemokine levels increased progressively with MV duration. Light microscopy showed increased leukocyte influx but no signs of alveolar leakage or albumin deposition. Electron microscopy revealed intact epithelial cell and basement membranes with sporadically minimal signs of partial endothelial detachment. In plasma, increased levels of IL-1alpha, tumor necrosis factor alpha, IL-6, and keratinocyte-derived chemokine were measured after MV. In the recovery animals, cytokine levels had normalized and no histologic alterations could be found. CONCLUSIONS: Mechanical ventilation induces reversible cytokine increase and leukocyte influx with preserved tissue integrity. This model offers opportunities to study the pathophysiologic mechanisms behind ventilator-induced lung injury and the contribution of MV to the "multiple-hit" concept. PMID- 17721245 TI - Neonatal exposure to a combination of N-methyl-D-aspartate and gamma-aminobutyric acid type A receptor anesthetic agents potentiates apoptotic neurodegeneration and persistent behavioral deficits. AB - BACKGROUND: During the brain growth spurt, the brain develops and modifies rapidly. In rodents this period is neonatal, spanning the first weeks of life, whereas in humans it begins during the third trimester and continues 2 yr. This study examined whether different anesthetic agents, alone and in combination, administered to neonate mice, can trigger apoptosis and whether behavioral deficits occur later in adulthood. METHODS: Ten-day-old mice were injected subcutaneously with ketamine (25 mg/kg), thiopental (5 mg/kg or 25 mg/kg), propofol (10 mg/kg or 60 mg/kg), a combination of ketamine (25 mg/kg) and thiopental (5 mg/kg), a combination of ketamine (25 mg/kg) and propofol (10 mg/kg), or control (saline). Fluoro-Jade staining revealed neurodegeneration 24 h after treatment. The behavioral tests--spontaneous behavior, radial arm maze, and elevated plus maze (before and after anxiolytic)--were conducted on mice aged 55 70 days. RESULTS: Coadministration of ketamine plus propofol or ketamine plus thiopental or a high dose of propofol alone significantly triggered apoptosis. Mice exposed to a combination of anesthetic agents or ketamine alone displayed disrupted spontaneous activity and learning. The anxiolytic action of diazepam was less effective when given to adult mice that were neonatally exposed to propofol. CONCLUSION: This study shows that both a gamma-aminobutyric acid type A agonist (thiopental or propofol) and an N-methyl-D-aspartate antagonist (ketamine) during a critical stage of brain development potentiated neonatal brain cell death and resulted in functional deficits in adulthood. The use of thiopental, propofol, and ketamine individually elicited no or only minor changes. PMID- 17721247 TI - Impact of the C2/C6 ratio of high-molecular-weight hydroxyethyl starch on pharmacokinetics and blood coagulation in pigs. AB - BACKGROUND: High-molecular-weight, low-substituted hydroxyethyl starch (HES) may not affect blood coagulation more than low-molecular-weight, low-substituted HES. The authors assessed in vivo the effect of a lowered C2/C6 ratio on pharmacokinetic characteristics and the impact on blood coagulation of high molecular-weight, low-substituted HES. METHODS: A prospective, randomized, parallel study in 30 pigs compared HES 650/0.42/2.8 with HES 650/0.42/5.6. Before, during, and after infusion of 30 ml/kg body weight HES, blood samples were collected over 630 min to measure HES concentrations and plasmatic coagulation and to assess blood coagulation in whole blood by Thrombelastography (TEG; Haemoscope Corporation, Niles, IL). Pharmacokinetic parameters were estimated using a two-compartment model. RESULTS: The elimination constant was 0.009 +/- 0.001 min(-1) for HES 650/0.42/2.8 and 0.007 +/- 0.001 min(-1) for HES 650/0.42/5.6 (P < 0.001); the area under the plasma concentration-time curve was 1,374 +/- 340 min x g/l for HES 650/0.42/2.8 and 1,697 +/- 411 min x g/l for HES 650/0.42/5.6 (P = 0.026). The measured plasma HES concentrations were not different between HES 650/0.42/2.8 and HES 650/0.42/5.6. Both HES solutions equally affected blood coagulation: Thrombelastographic coagulation index decreased similarly at the end of infusion of HES 650/0.42/2.8 and at the end of infusion of HES 650/0.42/5.6 (P = 0.293). Also, activated partial thromboplastin and prothrombin times increased similarly for HES 650/0.42/2.8 and HES 650/0.42/5.6 (P = 0.831). CONCLUSION: Reducing the C2/C6 ratio in high-molecular, low-substituted HES solutions results in a slightly faster HES elimination. However, the blood coagulation compromising effect was unaffected. PMID- 17721246 TI - Effects of the antimicrobial peptide LL-37 and hyperthermic preconditioning in septic rats. AB - BACKGROUND: The authors tested the effects of LL-37 prophylaxis or therapy on the outcome after intraabdominal sepsis and examined whether hyperthermic preconditioning plus LL-37 therapy augments host immune response and improves survival. METHODS: A rat model of peritoneal contamination and infection (PCI) with human stool was used to simulate clinical conditions. In trial 1, the authors compared (1) PCI, (2) LL-37 prophylaxis (0.5 mg/kg, 12 h before PCI), and (3) LL-37 therapy (0.5 mg/kg, 1 h after PCI). In trial 2, the authors compared (1) PCI, (2) LL-37 therapy, (3) hyperthermic preconditioning (41 degrees C for 1 h, 24 h before PCI), and (4) LL-37 therapy and hyperthermic preconditioning. The primary endpoint was mortality at 120 h. In trial 2, secondary endpoints were systemic levels of tumor necrosis factor alpha, interleukin 6, macrophage inflammatory protein 2, and heat shock protein 70; leukocyte counts; and neutrophil granulocyte phagocytosis. RESULTS: In trial 1, 30% of the control group compared with 70% of the LL-37 therapy group survived, but 55% after LL-37 prophylaxis survived (P = 0.038). In trial 2, 38% of the controls, 67% of the LL 37 therapy, 59% of the hyperthermic preconditioned, and 90% of the hyperthermic preconditioned plus LL-37 therapy group survived (P = 0.01). LL-37 therapy plus hyperthermic preconditioning reduced proinflammatory cytokine concentrations after sepsis; specifically compared with controls, macrophage inflammatory protein-2 and interleukin-6 levels were 1.5 +/- 1.5 versus 11 +/- 6 pg/ml (P = 0.028) and 13 +/- 8 versus 86 +/- 31 pg/ml, (P = 0.015), respectively. CONCLUSIONS: In this model of intraabdominal sepsis, LL-37 therapy improved outcome. Hyperthermic preconditioning per se was not successful, but in combination with LL-37 therapy, the survival rate after sepsis was increased and the proinflammatory cytokine response was downgraded. PMID- 17721248 TI - Altered contractile response due to increased beta3-adrenoceptor stimulation in diabetic cardiomyopathy: the role of nitric oxide synthase 1-derived nitric oxide. AB - BACKGROUND: In the diabetic heart, the positive inotropic response to beta adrenoceptor stimulation is altered and beta1 and beta2 adrenoceptors are down regulated, whereas beta3 adrenoceptor is up-regulated. In heart failure, beta3 adrenoceptor stimulation induces a negative inotropic effect that results from endothelial nitric oxide synthase (NOS3)-derived nitric oxide production. The objective of our study was to investigate the role of beta3-adrenoceptor in diabetic cardiomyopathy. METHODS: beta-Adrenergic responses were investigated in vivo (dobutamine echocardiography) and in vitro (left ventricular papillary muscle) in healthy and streptozotocin-induced diabetic rats. The effect of beta3 adrenoceptor inhibition on the inotropic response was studied in vitro. Immunoblots and NOS activities were performed in heart homogenates (electron paramagnetic resonance) and isolated cardiomyocytes. Data are mean percentage of baseline +/- SD. RESULTS: The impaired positive inotropic effect was confirmed in diabetes both in vivo (121 +/- 15% vs. 160 +/- 16%; P < 0.05) and in vitro (112 +/- 5% vs. 179 +/- 15%; P < 0.05). In healthy rat, the positive inotropic effect was not significantly modified in presence of beta3-adrenoceptor antagonist (174 +/- 20%), nonselective NOS inhibitor (N -nitro-l-arginine methylester [l-NAME]; 183 +/- 19%), or selective NOS1 inhibitor (vinyl-l-N-5-(1-imino-3-butenyl)-l ornithine [l-VNIO]; 172 +/- 13%). In diabetes, in parallel with the increase in beta3-adrenoceptor protein expression, the positive inotropic effect was partially restored by beta3-adrenoceptor antagonist (137 +/- 8%; P < 0.05), l NAME (133 +/- 11%; P < 0.05), or l-VNIO (130 +/- 13%; P < 0.05). Nitric oxide was exclusively produced by NOS1 within diabetic cardiomyocytes. NOS2 and NOS3 proteins were undetectable. CONCLUSIONS: beta3-Adrenoceptor is involved in altered positive inotropic response to beta-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by NOS1-derived nitric oxide in diabetic cardiomyocyte. PMID- 17721249 TI - Continuous preperitoneal infusion of ropivacaine provides effective analgesia and accelerates recovery after colorectal surgery: a randomized, double-blind, placebo-controlled study. AB - BACKGROUND: Blockade of parietal nociceptive afferents by the use of continuous wound infiltration with local anesthetics may be beneficial in a multimodal approach to postoperative pain management after major surgery. The role of continuous preperitoneal infusion of ropivacaine for pain relief and postoperative recovery after open colorectal resections was evaluated in a randomized, double-blinded, placebo-controlled trial. METHODS: After obtaining written informed consents, a multiholed wound catheter was placed by the surgeon in the preperitoneal space at the end of surgery in patients scheduled to undergo elective open colorectal resection by midline incision. They were thereafter randomly assigned to receive through the catheter either 0.2% ropivacaine (10-ml bolus followed by an infusion of 10 ml/h during 48 h) or the same protocol with 0.9% NaCl. In addition, all patients received patient-controlled intravenous morphine analgesia. RESULTS: Twenty-one patients were evaluated in each group. Compared with preperitoneal saline, ropivacaine infusion reduced morphine consumption during the first 72 h and improved pain relief at rest during 12 h and while coughing during 48 h. Sleep quality was also better during the first two postoperative nights. Time to recovery of bowel function (74 +/- 19 vs. 105 +/- 54 h; P = 0.02) and duration of hospital stay (115 +/- 25 vs. 147 +/- 53 h; P = 0.02) were significantly reduced in the ropivacaine group. Ropivacaine plasma concentrations remained below the level of toxicity. No side effects were observed. CONCLUSIONS: Continuous preperitoneal administration of 0.2% ropivacaine at 10 ml/h during 48 h after open colorectal resection reduced morphine consumption, improved pain relief, and accelerated postoperative recovery. PMID- 17721250 TI - Systemic antiinflammatory corticosteroid reduces mechanical pain behavior, sympathetic sprouting, and elevation of proinflammatory cytokines in a rat model of neuropathic pain. AB - BACKGROUND: Chronic pain models are commonly defined as either nerve-injury or inflammation models, but recent work suggests inflammatory processes are important in nerve injury-induced pain. METHODS: In the rat spinal nerve ligation model, the authors examined effects of systemic corticosteroid triamcinolone acetonide (TA) on the cytokine protein profile and sympathetic sprouting in the axotomized sensory ganglia, excitability of sensory neurons, and mechanical sensitivity. RESULTS: By postoperative day 3, marked increases (5- to 16-fold) in monocyte chemoattractant protein-1, growth-related oncogene (GRO/KC or CXCL1), and interleukin (IL)-6 were observed, whereas IL-4 and IL-2 levels fell more than fourfold. The increased cytokines and number of sympathetic basket formations in the sensory ganglia were reduced toward normal values by TA given starting at the time of injury. Interleukin-4 and IL-2 levels were not restored by TA. Systemic TA also reduced the firing rate and incidence of bursting activity, but not the overall incidence of spontaneous activity, in large- and medium-sized neurons. Mechanical hypersensitivity on postoperative day 3 was reduced by TA, and some effect could still be observed 4 days after cessation of TA. However, starting TA at day 7 was ineffective. CONCLUSIONS: Several components of the spinal nerve injury model are responsive to corticosteroid, suggesting inflammatory processes are important in the development of neuropathic pain. The observation that TA was effective when given starting at the time of injury suggests that steroid treatment might alter the development of chronic pain after surgical procedures that involve nerve injury, such as amputation or hernia repair. PMID- 17721251 TI - Effects of butorphanol on morphine-induced itch and analgesia in primates. AB - BACKGROUND: Butorphanol is an opioid analgesic with partial agonist actions at micro- and kappa-opioid receptors (MOR and KOR). Previous studies have demonstrated that both MOR antagonists and KOR agonists are effective in alleviating intrathecal morphine-induced itch in primates. The aim of the study was to investigate the effectiveness of butorphanol as an antipruritic and to elucidate the receptor mechanisms underlying butorphanol's antipruritic effect in primates. METHODS: Adult rhesus monkeys were used in the behavioral assays for measuring itch/scratching and analgesia. The dose-response curves of butorphanol were studied using selective MOR and KOR antagonists. In addition, the effect of butorphanol as an antipruritic was studied on subcutaneous and intrathecal morphine-induced itch and analgesia. KOR-selective antagonists were further used to compare the degrees of MOR and KOR activation underlying the antipruritic effect of butorphanol. RESULTS: Butorphanol alone produced analgesia with slight itch responses, and both effects were blocked by a MOR antagonist, clocinnamox (0.1 mg/kg). In contrast, a KOR antagonist, 5'-guanidinylnaltrindole (1 mg/kg), increased butorphanol-elicited itch. Systemic butorphanol (0.0032-0.032 mg/kg) dose-dependently attenuated systemic or intrathecal morphine-induced itch. In addition, butorphanol either potentiated or maintained morphine-induced analgesia without producing sedation. KOR-selective antagonists, 5'-guanidinylnaltrindole (1 mg/kg) and nor-binaltorphimine (3.2 mg/kg), only partially reversed the antipruritic effect of butorphanol with different durations of KOR antagonism. CONCLUSIONS: Butorphanol is effective in attenuating systemic or spinal morphine induced itch without reducing morphine analgesia. This study provides functional evidence that both partial MOR and KOR agonist actions contribute to the effectiveness of butorphanol as an antipruritic in primates. PMID- 17721252 TI - Effects of topical application of clonidine cream on pain behaviors and spinal Fos protein expression in rat models of neuropathic pain, postoperative pain, and inflammatory pain. AB - BACKGROUND: Clonidine can effectively reduce pain and/or hypersensitivity. However, the antihypersensitivity effects of clonidine topically applied in cream (CC) have not been investigated. The authors evaluated effects of topical application of CC on pain behaviors and spinal Fos-like immunoreactivity in rats with hypersensitivity. METHODS: Clonidine (30, 100, and 300 microg/g) was prepared in a cream base. In rat models of neuropathic pain, inflammatory pain, and postoperative pain, the authors evaluated effects of CC (0.1 g), topically applied onto the plantar surface of the injured or uninjured paw, on thermal hyperalgesia and mechanical allodynia to von Frey filaments. The authors also evaluated effects of CC on lumbar spinal Fos-like immunoreactivity. RESULTS: In neuropathic rats, CC applied onto the injured paw reduced thermal hyperalgesia and mechanical allodynia dose dependently, whereas CC applied onto the uninjured paw had no effect. The antihypersensitivity effects of CC were antagonized by intraperitoneal yohimbine (10 mg/kg). Further, CC reduced Fos-like immunoreactivity in neuropathic rats. In contrast, CC in a single dose had no effects on hyperalgesia, allodynia, or Fos-like immunoreactivity in rats with inflammatory or postoperative pain. In rats with postoperative pain, CC repeatedly applied for 6 days reduced thermal hyperalgesia, but not mechanical allodynia, in the postoperative days, whereas it had no effects on hyperalgesia or allodynia in those with inflammatory pain. CONCLUSIONS: Topical CC in concentrations examined significantly reduced hypersensitivity and lumbar spinal Fos-like immunoreactivity in rats with neuropathic pain, probably through activation of peripherally located alpha2 adrenoceptors. However, CC was only partially effective and totally ineffective in rats with postoperative pain and inflammatory pain, respectively. PMID- 17721254 TI - Sedation and anesthesia care for ophthalmologic surgery during local/regional anesthesia. AB - Anesthesia care for the patients undergoing ophthalmologic surgical procedures during local/regional anesthesia balances goals of patient comfort with safety and an optimal outcome in a highly cost-conscious environment. This article discusses current practices and trends in anesthesia care with respect to sedation for eye surgery during local/regional anesthesia. Although there is no evidence that one local/regional anesthesia technique or sedation analgesia regimen is superior to the others, this review highlights important differences between these varied approaches. The type of block used for the ophthalmologic surgery alters the sedation requirements. Changes in surgical techniques have increased the popularity of topical anesthesia, which reduces the need for sedation analgesia and may lessen the need for an anesthesia practitioner. The involvement of an anesthesia practitioner in eye surgery varies from facility to facility based on costs, anesthesiologist availability, and local standards. Anesthesia care choices are often made based on surgeon skill and anesthesiologist comfort, as well as the expectations and needs of the patient. PMID- 17721253 TI - Differential contribution of sodium channel subtypes to action potential generation in unmyelinated human C-type nerve fibers. AB - BACKGROUND: Multiple voltage-dependent sodium channels (Na(v)) contribute to action potentials and excitability of primary nociceptive neurons. The aim of the current study was to characterize subtypes of Na(v) that contribute to action potential generation in peripheral unmyelinated human C-type nerve fibers. METHODS: Registration of C-fiber compound action potentials and determination of membrane threshold was performed by a computerized threshold tracking program. Nerve fibers were stimulated with a 1-ms current pulse either alone or after a small ramp current lasting 300 ms. RESULTS: Compound C-fiber action potentials elicited by supramaximal 1-ms current pulses were rather resistant to application of tetrodotoxin (30-90 nM). However, the same concentrations of tetrodotoxin strongly reduced the peak height and elevated membrane threshold of action potentials evoked at the end of a 300-ms current ramp. A similar effect was observed during application of lidocaine and mexiletine (50 microM each). CONCLUSIONS: These data indicate that more than one type of Na(v) contributes to the generation of action potentials in unmyelinated human C-type nerve fibers. The peak height of an action potential produced by a short electrical impulse is dependent on the activation of tetrodotoxin-resistant ion channels. In contrast, membrane threshold and action potential peak height at the end of a slow membrane depolarization are regulated by a subtype of Na(v) with high sensitivity to low concentrations of tetrodotoxin, lidocaine, and mexiletine. The electrophysiologic and pharmacologic characteristics may indicate the functional activity of the Na(v) 1.7 subtype of voltage-dependent sodium channels. PMID- 17721258 TI - Mortality related to anesthesia and sleep deprivation in medical doctors. PMID- 17721256 TI - Similarity of operation times for common general surgical procedures in the United Kingdom and the United States. PMID- 17721255 TI - Histopathologic features of fat embolism in fulminant fat embolism syndrome. PMID- 17721260 TI - Disruption of water trap from leak of isoflurane during the vaporizer filling process in the Drager Apollo. PMID- 17721261 TI - Tega-dermabrasion. PMID- 17721262 TI - Lipid reversal of central nervous system symptoms of bupivacaine toxicity. PMID- 17721263 TI - Perioperative thrombotic risk of coronary artery stents: possible role for intravenous platelet blockade. PMID- 17721265 TI - Begin at the beginning, with the tissue! The key message underlying the ASCO/CAP Task-force Guideline Recommendations for HER2 testing. PMID- 17721266 TI - Terminal respiratory unit type lung adenocarcinoma is associated with distinctive EGFR immunoreactivity and EGFR mutations. AB - Approximately 10% to 20% of nonsmall cell lung cancer patients respond to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, such as gefitinib. Responders are mostly nonsmokers and women with tumors displaying bronchioloalveolar features. Mutations of the tyrosine kinase domain of the EGFR gene have been associated with a clinical response to gefitinib. A recent study reported that the terminal respiratory unit (TRU)-type adenocarcinoma shares the clinical profile and EGFR mutations of gefitinib responders. EGFR immunoreactivity in this context has not been reported in the literature. We performed a detailed immunohistochemical analysis of EGFR expression on 124 consecutive lung resection specimens for malignancy, to survey the EGFR immunoreactivity in lung cancers in general and to correlate EGFR immunoreactivity with EGFR mutations and TRU-type histology. EGFR positivity was seen most frequently in squamous cell carcinomas (77%), followed by TRU-type adenocarcinomas (63%), large cell carcinomas (23%), and non-TRU-type adenocarcinomas (12%). A distinctive basally oriented cytoplasmic positivity was observed exclusively in TRU-type adenocarcinomas. EGFR mutation was identified in 6 of 54 cases studied and all 6 cases were TRU-type adenocarcinomas. Five of six cases with EGFR mutation were positive for EGFR immunostain with the basal cytoplasmic localization. In conclusion, EGFR immunoreactivity with basal cytoplasmic pattern was exclusively seen in TRU-type adenocarcinoma and a subset of these cases was seen with EGFR mutations in the responders to EGFR inhibitor therapy. PMID- 17721267 TI - Correlation of plasma cell percentages by CD138 immunohistochemistry, cyclin D1 status, and CD56 expression with clinical parameters and overall survival in plasma cell myeloma. AB - CONTEXT: Plasma cell myelomas (PCMs) are traditionally diagnosed by the percentage (%) of plasma cells (PCs) in the bone marrow aspirate differential combined with clinical parameters and radiographic findings. PCs are most reliably quantitated in bone marrow (BM) tissues by CD138 immunohistochemistry (IHC). However, there are no correlations of % CD138+ cells with clinical parameters or overall survival (OS). The presence of cyclin D1 has correlated with worst prognosis, but cyclin D1 has not been correlated with routine cytogenetics. CD56+, although not significantly reported in reactive plasmacytoses, monoclonal gammopathy of undetermined significance (MGUS), nor in lymphoplasmacytic lymphomas (LPLs), has not been evaluated in borderline diagnostic (borderline) cases. OBJECTIVES: It includes: (1) correlating the percentages of PCs by CD138 IHC, cyclin D1 status, and CD56 expression with clinical parameters and OS in PCMs, (2) correlating cyclin D1 status with routine cytogenetics in PCMs, borderline cases, and MGUSs, and (3) analyzing CD56 expression in PCMs, borderline cases, MGUSs, and LPLs. DESIGN: Bone marrow aspirates, BM touch preparations, and BM clot and/or biopsy sections with CD138/kappa/lambda IHC (44-PCMs, 9-MGUSs, 17-borderline cases, 3-LPLs, and 3 reactive plasmacytoses) were reviewed and stained with CD56 and cyclin D1. RESULTS/CONCLUSIONS: Increased CD138+ cells did not correlate significantly with clinical parameters or OS. Cyclin D1+ did not correlate with the presence of a t(11;14) by routine cytogenetics [although detected in all t(11;14)+ cases], clinical parameters, nor OS. CD56 expression was identified in PCMs, MGUSs, and LPL but not in reactive plasmacytoses. CD56+ did not distinguish PCMs, MGUS, and LPLs, and did not correlate with clinical parameters or OS. CD56 and cyclin D1 IHC were better evaluated in BM clot than biopsy sections. PMID- 17721268 TI - COX-2 expression in invasive breast cancer: correlation with prognostic parameters and outcome. AB - Lipoxygenases (LOX) and cyclooxygenases (COX) are key mediators of arachidonic acid metabolism. Recently, studies have reported that human breast carcinomas aberrantly express LOX and cyclooxygenase-2 (COX-2), and that decreased levels of 15-lipoxygenase (15-LOX) and raised levels of COX-2 and 12-LOX have prognostic value in patients with breast cancer. 15-LOX was significantly reduced with increasing stage, and in patients who developed metastatic disease, local recurrence, and/or died. With high COX-2, patients developed local recurrence, died from breast cancer and had reduced disease-free and disease-related overall survival in estrogen receptor (ER)-negative but not ER-positive disease. COX-2 expression is also associated with increased angiogenesis, lymph node metastasis, and Her2-neu overexpression. The purpose of this study is to evaluate COX-2 expression in breast cancer and to determine its correlation with prognostic parameters and outcome. Five tissue microarrays were constructed from 43 breast carcinomas and 5 normal breast tissues, represented by 1 mm cores in triplicate from each of 3 foci. Tissue microarray cores were immunostained with monoclonal COX-2. Expression was assessed as intensity and scored as percentage of cells positive. Prognostic parameters and follow-up information were obtained from the hospital records of Mexican Oncology Hospital, Mexico, where the carcinomas were diagnosed. Ninety-five percent (41/43) of the breast carcinomas showed cytoplasmic COX-2 expression. COX-2 intensity and percentage of cells positive correlated significantly with size of carcinoma (P=0.0271; P=0.0539, respectively). COX-2 intensity correlated significantly with histologic grade (P=0.0182). COX-2 did not correlate with outcome (disease-free and overall survival). There was no significant correlation between COX-2 and ER. In conclusion, COX-2 correlates with poor prognostic markers in breast cancer (large tumor size and high tumor grade), but not with outcome. The therapeutic value of COX-2 inhibitors in COX-2 positive breast cancer patients requires further investigation. PMID- 17721269 TI - The spectrum of morphomolecular abnormalities of the E-cadherin/catenin complex in pleomorphic lobular carcinoma of the breast. AB - Pleomorphic lobular carcinoma of the breast is a high nuclear grade variant of lobular carcinoma. E-cadherin, a tumor-invasion suppressor gene, codes for a transmembrane protein that functions in intercellular adhesion. The E-cadherin protein internal domain binds with alpha, beta, gamma, and p120 catenins to anchor the E-cadherin complex to the actin cytoskeleton of the cell. The E cadherin gene is routinely mutated in lobular neoplasia. This study examines the morphomolecular spectrum of the components of the E-cadherin-catenin complex in lobular neoplasia. Fifteen cases of pleomorphic lobular neoplasia, 8 cases of classic lobular neoplasia and 4 ductal carcinomas were studied. Normal breast epithelium and invasive ductal carcinomas all showed intense linear cell membrane immunostaining with antibodies to E-cadherin, alpha, beta, gamma, and P120 catenins. Membrane immunostaining of the catenin antibodies in lobular neoplasia was negative, except for rare cases that displayed beaded or dotlike patterns. Cytoplasmic immunostaining patterns for all lobular lesions included coarse paranuclear granules of beta catenin or diffuse intense cytoplasmic staining for P120 catenin. These immunostaining patterns demonstrate that catenins alpha, beta, gamma, and p120 are routinely dislocated from the cell membrane into the cytoplasm in lobular neoplasia and that the disrupted catenin patterns parallel absence of membrane E-cadherin in all cases. The diffuse cytoplasmic immunostaining of p120 in lobular neoplasia may be useful diagnostically as a positive marker for lobular neoplasia. PMID- 17721270 TI - High labeling indices of cdc25B is linked to progression of gastric cancers and associated with a poor prognosis. AB - To clarify the significance of cdc25B, which plays an important physiologic role in regulation of the G2/M check point, in progression of gastric cancer, 125 samples of paraffin-embedded gastric cancers were investigated by immunohistochemistry. In addition, 3 human gastric cancer cell lines were studied to determine the cellular localization of cdc25B by immunohistochemistry and cell fractionation followed by Western blotting. In the cell lines cdc25B was found to be present in both nuclei and cytoplasm, but predominantly in nuclei. High labeling indices of cdc25B in invasion front of gastric cancer was observed in 31 out of 125 cases (24.8%), linked to an advanced depth of cancer invasion (P=0.02), high rates of lymphatic invasion (P=0.03), and lymph node metastasis (P<0.01). Furthermore, the Kaplan-Meier method demonstrated a poor prognosis for cdc25B high labeling indices cases (P=0.02), although multivariate analysis revealed it not to be an independent factor. In conclusion, it seems likely that cdc25B is located predominantly in nuclei when overexpressed and this has some linkage with progression of gastric cancer. PMID- 17721271 TI - Immunolocalization of beta-catenin in pleomorphic adenomas and carcinomas ex pleomorphic adenomas of salivary glands. AB - Beta-catenin plays a central role in cadherin/catenin cell-cell adhesion complex and is involved in cell signaling pathway. Change in beta-catenin distribution has been associated with several human cancers including salivary gland tumors. We studied the immunolocalization of beta-catenin in a series of pleomorphic adenomas (PA) and carcinomas ex-pleomorphic adenomas (Ca ex-PA). Ten samples of PA and ten of Ca ex-PA were evaluated by immunohistochemistry using streptavidin biotin-peroxidase technique and a monoclonal antibody against beta-catenin (E-5). Cell membrane/cytoplasmic staining of beta-catenin was observed in normal gland parenchyma, PA, and in well-differentiated Ca ex-PA. Cytoplasmic/nuclear beta catenin staining was observed in poorly differentiated carcinomas and, interestingly, in one case of PA. Our data showed decreased cell membrane beta catenin expression in higher-grade tumors suggesting that beta-catenin may play an important role in histologic differentiation and transition to malignant phenotype of Ca ex-PA. PMID- 17721272 TI - p16INK4a expression in invasive vulvar squamous cell carcinoma. AB - p16, a member of the INK4a family of cyclin-dependent kinase inhibitors, is known as a negative regulator of cell cycle progression and differentiation. Although p16 has been shown to be a promising biomarker for the detection of cervical intraepithelial neoplasia, few data have been published on vulvar cancer. Using immunohistochemistry, we evaluated the expression of p16 in 80 cases of invasive vulvar squamous cell carcinoma. Results were correlated with clinicopathologic parameters and survival data to determine the prognostic significance of p16 in vulvar cancer. p16 expression was detected in 34 of 80 (43%) cases of invasive vulvar squamous cell carcinoma. The expression was localized to the cytoplasm and the nuclei of the tumor cells. Correlations between p16 expression status and any clinicopathologic variables failed to be of statistical significance. In a univariate analysis, groin lymph node status, tumor stage, and tumor grade were associated with disease-free and overall survival, respectively. Patients positive for p16 expression showed a significantly longer disease-free and overall survival by univariate analysis. p16 expression was not associated with survival in a multivariate Cox-regression model. Our data add on those published in the literature and suggest that p16 may be of prognostic significance in invasive vulvar squamous cell carcinoma. PMID- 17721273 TI - Effect of tamoxifen on endometrial histology, hormone receptors, and cervical cytology: a prospective study with follow-up. AB - OBJECTIVES: Our major hypothesis for these studies was that tamoxifen's varied effects on the endometrium might be due in part to differences in effect on estrogen and progesterone receptors [ER, progesterone receptor isoform A (PRA), and progesterone receptor isoform B (PRB)]. We aimed to evaluate the changes in histology in serial endometrial biopsies (Em bx), Papanicolaou smears (Pap smears), and endometrial ultrasounds as well as changes in the expression of ER, PRA, and PRB in response to tamoxifen. We propose that understanding and correlating the dynamics of receptor expression with histologic and cytologic changes will help us better understand the effect of tamoxifen on the endometrium and its role in the development of endometrial carcinoma in some patients. METHODS: Forty-two patients to be started on tamoxifen underwent a pretreatment Em bx and Pap smear. Follow-up serial Em bxs and Pap smears were obtained at sixth month and then at yearly intervals for up to 6 biopsies per case. Maturation indices (MIs) were determined on the Pap smears, and ER, PRA, and PRB immunostains were performed on the biopsies. Follow-up data is for a maximum of 10 years. Trends in changes in endometrial histology were analyzed and when atrophic or inactive endometrium changed to proliferative endometrium on treatment it was considered to be an increase in estrogen effect and the vice versa changes as a decrease in estrogen effect. RESULTS: None of the subjects developed hyperplasia or malignancy. Two patients' Em bx demonstrated atypical cells associated with eosinophilic metaplasia, but subsequent biopsies had no atypia. Of the 42 patients, 37 had serial Em bxs in which evaluation for trends could be performed. Twelve of 37 (32.4%) had an overall decrease in estrogen effect on endometrial histology with another 12/37 (32.4%) showing no estrogenic effect on endometrial histology. Six of 37 patients (16.2%) showed an increased estrogen effect on endometrial histology. Seven of 37 (18.9%) had variable endometrial histology with no definable pattern. There was a statistically significant increase in PRA expression compared with baseline as time progressed (P<0.05). The PRB showed a contrasting significant decrease in expression at 2.5 and 3.5 years (P<0.05). There was no significant change in ER expression over the course of the study (P>0.05). Seven of 12 (58.3%) with a decreased estrogenic effect on endometrial histology had a concordant decrease in PRB expression. Seven of 12 (58.3%) with no change in endometrial histology also had a concordant decrease in PRB expression. Comparing the MI of Pap smears with histologic activity of the endometrium revealed minimal correlation between the two. However, in the patients with an increased estrogen effect on endometrial histologic activity, there was no correlation with the MI. Additionally, 57% of patients showed no correlation between endometrial histologic activity and ultrasound findings. CONCLUSIONS: Tamoxifen had an antiestrogenic or neutral effect on endometrial histology and Pap smears of most subjects, but estrogenic, or variable effects were also observed in a minority of patients. Tamoxifen treatment was accompanied by an uncoupling of the regulation of PRA and PRB expression without effect on ER expression. Overall, expression of PRB decreased whereas that of PRA increased. PMID- 17721274 TI - Immunohistochemical expression of Sonic hedgehog in intraductal papillary mucinous tumor of the pancreas. AB - Aberrant expression of Sonic hedgehog (Shh) has been reported in many human cancers including ductal carcinoma of the pancreas. The intraductal papillary mucinous tumor (IPMT) has been considered as one of the precursor lesions of invasive ductal carcinoma of the pancreas. Shh expression in pancreatic IPMT has not been reported. We investigated an immunohistochemical (IHC) expression of Shh in 55 cases of pancreatic IPMT. We analyzed the IHC expression of Shh in the following histologic grades of tumor: adenoma (AD), moderate dysplasia (MD), noninvasive carcinoma (NIC), and invasive carcinoma (IC), and with the following histologic subtype classification: intestinal, pancreatobiliary, null, and unclassifiable type. IHC Shh expression was noted in 6 (46.2%) of 13 AD, 5 (35.7%) of 14 MD, 12 (80%) of 15 NIC, and 11 (84.6%) of 13 IC. Shh expression was significantly increased in malignant IPMT (NIC+IC) compared with nonmalignant IPMT (AD+MD) (82.1% vs. 40.7%, P=0.0005). IHC Shh expression was found in 11 (68.8%) of 16 intestinal types, 13 (92.8%) of 14 pancreatobiliary types, 8 (38.1%) of 21 null types, and 2 (50%) of 4 unclassifiable types. Intestinal and pancreatobiliary subtypes showed a high expression of Shh compared with the null and unclassifiable type of IPMT. All 3 cases of node metastasis showed IHC Shh expression in tumor cells of metastatic lymph nodes. Therefore, Shh expression may have a critical role in the late stage of carcinogenesis of IPMT, and may impact metastatic progression to the lymph nodes in malignant IPMT. PMID- 17721275 TI - Histologic and immunohistochemical changes in the stented common bile duct. AB - Many patients with pancreatic carcinoma have stent placement for biliary obstruction before resection. Stent-associated atypia, found in common bile duct (CBD) margins at the time of resection, may be confused with malignancy. We evaluated histologic and immunohistochemical changes in CBD margins from resection specimens for pancreatic carcinoma. Histologic findings in CBDs, including ulcer and inflammation; epithelial metaplasia, atypia, and gland complexity; and increased wall thickness, nerve entrapment, and smooth muscle content, were compared in 30 stented and 31 nonstented CBD margins from pancreaticoduodenectomies for carcinoma and 13 normal CBDs from autopsy material. The proliferation index was calculated for stented and nonstented CBDs after Ki 67 immunohistochemical staining. Immunostaining for Ki-67, p53, and c-erbB-2 was performed in stented CBDs and corresponding carcinomas. All the histologic changes occurred more frequently in stented and nonstented CBD margins from carcinoma patients than in normal CBDs. Stented CBDs had significantly increased epithelial changes and Ki-67 proliferation rate as compared with nonstented CBDs. The stented CBDs had significantly less p53 and c-erbB-2 expression as compared with corresponding pancreatic carcinomas. Caution should be applied when interpreting atypia in CBD margins from patients with a history of CBD stenting. Changes found in stented CBDs are characteristic, and in most cases can be distinguished from malignancy. In difficult cases, immunohistochemistry may be useful. PMID- 17721276 TI - Comparison of the Dako EGFR pharmDx kit and Zymed EGFR antibody for assessment of EGFR status in colorectal adenocarcinoma. AB - Immunohistochemistry is widely used to assess epidermal growth factor receptor (EGFR) expression on colorectal carcinomas to select patients for treatment with cetuximab, an anti-EGFR antibody. The data comparing different commercial EGFR antibodies is limited, and no cost comparisons have been made. We analyzed 65 advanced colorectal cancers from 36 patients using the EGFR pharmDx kit (DakoCytomation) and Clone 31G7 (Zymed Laboratories, Inc). EGFR expression was seen in 35 (53%) tumors (21 primary, 14 metastatic) with the Dako pharmDx kit. The Zymed antibody showed positive results in 41 (63%) tumors (25 primary, 16 metastatic). The cost per test was $40.00 with the pharmDx kit and $3.52 with the Zymed antibody. The Zymed antibody detects 10% more cases of colorectal cancer as EGFR positive, and is 10 times cheaper than the Dako pharmDx kit. There is little justification for the use of expensive kits for testing EGFR expression, when other available antibodies without the kit can give comparable or superior results. PMID- 17721277 TI - Expression of renal cell carcinoma antigen (RCC) in renal epithelial and nonrenal tumors: diagnostic Implications. AB - Antibody to renal cell carcinoma (RCC) antigen, a normal human proximal brush border antigen, has recently become commercially available and reported to be highly specific and a relatively sensitive marker for RCC. Of the nonrenal tumors occasional carcinomas have been reported to express RCC, notably breast carcinoma. Using tissue microarrays, we investigated the use of RCC on a large number of renal epithelial neoplasms (RENs) and nonrenal tumors, especially those potentially confused with REN. Three tissue microarrays containing 241 REN samples, 192 samples of a wide variety of neoplasms and 170 adrenal tumor samples, respectively, were stained with RCC monoclonal antibody. RCC expression was scored for staining intensity and percentage expression. Out of 241 REN, 173 were positive for RCC (sensitivity 72%): clear cell 72%, papillary 95%, chromophobe 91%, unclassified 85%, oncocytoma 75%, sarcomatoid 20%, and metastatic RCC 40%. The overall immunostaining intensity was consistently much higher in papillary and clear cell RCC than in other tumors. Seventy-six out of 362 nonrenal tumor samples demonstrated either focal or diffuse expression for RCC (specificity 79%). These included: adrenocortical neoplasms 37/170 (22%), colonic 11/29 (37.5%), breast 9/27 (33%), prostate 5/18 (27.7%), ovary 2/17 (11.7%), melanoma 3/18 (16.6%), lung 3/21 (14.2%), and parathyroid 3/3 (100%). RCC expression was seen equally among adrenal adenoma and carcinoma group. Eight out of 28 (28.5%) normal adrenal cores also stained for RCC. RCC is a relatively useful marker in the differential diagnosis of REN only if used in a panel with other positive and negative markers. RCC does not reliably differentiate REN, especially classic clear cell type, from adrenocortical neoplasms, which are frequently confused due to close anatomic proximity and similar morphology. RCC also does not reliably differentiate subtypes of renal epithelial neoplasms. PMID- 17721278 TI - PGDS, a novel technique combining chromogenic in situ hybridization and immunohistochemistry for the assessment of ErbB2 (HER2/neu) status in breast cancer. AB - Given the important prognostic and predictive utility of v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (ErbB2) [human epidermal growth factor receptor 2 (HER2/neu)] in breast cancer, it is recommended that ErbB2 testing be performed on all invasive breast cancers at the time of diagnosis. A consensus, however, has not yet been reached as to the optimal method of evaluating ErbB2 status. Immunohistochemistry to detect protein overexpression and fluorescence in situ hybridization (FISH) to detect ErbB2 gene amplification are the most frequently used methods. As no one detection method fulfills all necessary requirements of reliability, reproducibility, and ease of use, we developed a novel approach in the form of a simple assay we refer to as protein and gene double staining (PGDS) which simultaneously evaluates protein overexpression and gene amplification by combining immunohistochemistry with chromogenic in situ hybridization (CISH). A total of 134 invasive breast carcinomas, including 81 cases with a full-face section and 53 cases included in a tissue microarray (TMA), were assessed by PGDS, and the results were correlated with ErbB2 gene amplification status as determined by FISH. ErbB2 gene copy number determined by CISH analysis in the PGDS assay showed excellent concordance with that of FISH (correlation coefficient 0.82; P<0.001 with full-face section cases, and 0.98; P<0.001 with cases in a TMA). The overall concordance rate for gene amplification status between PGDS and FISH was 90.12% in cases with a full-face section and 92.45% with TMA cases. Perfect correlation was seen between the PGDS assay and FISH in cases that were considered either nonamplified or highly amplified by the dual assay. Of the 17 cases that showed low amplification by PGDS, 5 were classified as nonamplified by FISH. Correction for chromosome 17 copy number in the FISH assessment contributed to the discordance between CISH and FISH results. This newly developed PGDS method represents a novel approach to ErbB2 status determination that combines the assessment of both protein overexpression and gene amplification in one simple assay. It is likely that this assay will aid in immunohistochemical calibration and will also increase the sensitivity and specificity of ErbB2 testing. PMID- 17721279 TI - Development of standard estrogen and progesterone receptor immunohistochemical assays for selection of patients for antihormonal therapy. AB - Estrogen receptor (ER) and progesterone receptor (PR) status in breast carcinomas are considered validated predictive factors for selecting patients for antihormonal therapy. Published surveys have shown a significant rate of disagreement and lack of reproducibility of immunohistochemistry (IHC) results from laboratories around the world. To address these limitations IHC assays for ER and PR were developed using characterized reagents, after careful calibration of the sensitivity and specificity to match established assays previously validated in large clinical studies. The ER assay uses a cocktail of 2 mouse monoclonal antibodies (1D5 and ER-2-123) and the PR assay uses 1 mouse monoclonal antibody (PgR 1294); both are followed by a polymer-peroxidase-based detection system. All antibodies were tested for specificity by epitope mapping. The sensitivity of the new assays was calibrated to be equivalent to previously validated IHC assays followed by a comparison with the validated assays in a concordance study involving over 200 specimens. All slides were scored with the "Allred Score," also used for scoring of the original validated assays. The overall concordance between the new and the established IHC assays was nearly perfect (99%). The concordance study demonstrated greater than 98% positive agreement and 100% negative agreement of the new IHC assays with the previously validated IHC assays. This equivalence establishes the clinical validation of the assays and, as they are based on newer generation reagents and are produced and tested under stringent quality control conditions to ensure their consistency, they add additional advantages to the user and patients. PMID- 17721280 TI - Probe production for in situ hybridization by PCR and subsequent covalent labeling with fluorescent dyes. AB - A simple procedure for fluorescent labeling of probes just before in situ hybridization is provided. Aminoallyl-dUTP is introduced during probe production by polymerase chain reaction (PCR). The aminoallyl-dUTP functions as a reactive site for subsequent labeling of the probe. Activated fluorescent dyes such as fluorescein are covalently attached to the probe through the formation of a stable amide bond. Labeled probes are purified by size-exclusion gel chromatography to remove unincorporated dye. Target genes used to demonstrate the efficacy of this technique with in situ hybridization are rat Y-chromosome and rat granulocyte colony-stimulating factor receptor. PCR amplicons containing aminoallyl-dUTP were produced in high yield. Probes obtained after labeling with activated fluorophores demonstrated high intrinsic activity within in situ hybridizations. The introduction of aminoallyl-dUTP into the PCR reaction enables the production of "unlabeled" probes by PCR having a shelf life, which is not limited by the storage and stability challenges of fluorophore-labeled probes. Subsequent labeling of the probes with activated fluorescent dyes just before use allows one step in situ hybridization with high activity and minimal background staining. PMID- 17721281 TI - Real-time PCR analysis of RNA extracted from formalin-fixed and paraffin-embeded tissues: effects of the fixation on outcome reliability. AB - In many pathologic circumstances, quantitative mRNA expression levels are important for evaluation of possible genome mutations. The development of real time polymerase chain reaction (RT-PCR) technology has facilitated the realization of nucleic acid quantification. Potentially, quantitative PCR offers a number of advantages over traditional methods because it permits the use of small amounts of genetic material. In the present study, we optimize a RNA purification technique on specimens that are formalin-fixed, paraffin-embedded and we examine prolonged formalin fixation effects on quantitative RT-PCR analysis. We compared RNA levels with 70 colic mucosa samples using the cyclooxygenase 2 gene as marker. The difference in amplification successes between formalin-fixed tissues and formalin-fixed, paraffin-embedded tissues was not statistically significant. Moreover, we compared the expression of formalin fixed samples with the expression of each fresh tissue. Wilcoxon Mann-Whitney test shows that only the difference in the expression levels of 1- or 3-hour formalin-fixed samples is not statistically significant with respect to other fixation times. We found that the mRNA can be reliably extracted from formalin fixed, paraffin-embedded tissue sections but that prolonged formalin fixation produces different results in quantitative RT-PCR. It can be related to difference in RNA sequences length and the generation of secondary structures that are more susceptible to the prolonged formalin fixation. We suppose that the paraffin do not influence the RNA extraction yield because there are no statistical significant differences between amplification success of formalin fixed tissues and paraffin-embedded tissues. Therefore, in relative expression quantization, we confirm that it is appropriate to use specimens with same protocols and time for formalin fixation. PMID- 17721282 TI - Increasing the efficiency of paraffin tissue microarrays by packing the paraffin tissue core biopsies in a honeycomb pattern. AB - Paraffin tissue microarrays (PTMAs) are blocks of paraffin holding up to 1000 paraffin tissue core biopsies (PTCBs) for high throughput molecular analysis. The number of PTCBs in a PTMA depends on the surface area of the PTMA, the diameter of and the distance between the PTCBs and on their arrangement inside the assembled PTMA. The PTCBs are usually arranged in a rectangular x-y pattern of rows and columns. This design facilitates the construction of a PTMA because the operator simply turns the wheels of an x-y-table for a set, unchanging distance. The evaluation of the stained sections is also relatively easy. However, this rectangular arrangement means wasted space in the PTMA. To reclaim this space, the PTCBs could be arranged in a honeycomblike pattern. For every 8 rows in the conventional rectangular arrangement, 1 additional row of PTCBs can be packed. However, the researcher has to become accustomed to this uncommon arrangement when filling and evaluating the PTMA. Automatic slide readers and specially designed computer programs for the digital evaluation of the PTMAs can be helpful. In summary, the arrangement of PTCBs in a honeycomblike pattern increases the density and number of specimens stored in a PTMA, thereby enhancing its efficiency. PMID- 17721283 TI - Intra-abdominal follicular dendritic cell sarcoma with marked pleomorphic features and aberrant expression of neuroendocrine markers: report of a case with immunohistochemical analysis. AB - Follicular dendritic cell sarcoma (FDCS) is a very rare malignant tumor arising most frequently in lymph nodes with only few reports of extranodal locations. We report the case of a 35-year-old man with a large retroperitoneal mass. Histologically the tumor was composed of highly pleomorphic cells exhibiting some uncommon features such as an epithelioid appearance, cystic spaces, and multinucleated cells with morphologic features of emperipolesis. Immunohistochemically the neoplastic cells were immunoreactive for CD21, CD23 and CD35. A previously unreported expression of neuroendocrine markers (Synaptophisyn and Neuron-Specific-Enolase) was present. Ultrastructurally no neuroendocrine secretory granules were detected. FDCS can mimic a wide variety of other malignant tumors, and a correct diagnosis requires exclusion of other neoplasms and immunohistochemical confirmation. PMID- 17721285 TI - A simple approach to the repeatability of the Schirmer test without anesthesia: eyes open or closed? AB - PURPOSE: To compare the repeatability of the Schirmer test (ST) administered with the eyes open (STo) with the repeatability of the ST administered with the eyes closed (STc). METHODS: STo and STc without anesthesia were alternately applied with 1-day intervals for a total of 6 times on 28 eyes of 14 healthy volunteers. The intraclass correlation coefficients (ICCs) and their 95% confidence intervals (CIs) were calculated to assess test-retest reliability of the STo and STc. RESULTS: STc scores were found to be statistically lower than the STo scores in general (right eyes: t = 2.033, P = 0.048; left eyes: t = 3.474, P = 0.004). The ICC was 0.632 (right eyes) and 0.618 (left eyes) for STo and 0.943 (right eyes) and 0.933 (left eyes) for STc. CONCLUSIONS: Our study suggests that administering the ST with the patient's eyes closed produces less variable results and more repeatability than STo in normal subjects. Although our results may not extend to dry eye patient populations, we propose that STc without anesthesia can be considered by those ophthalmologists who frequently use the ST as an adjunct to the differential diagnosis of dry eye in patients presenting with ocular discomfort, making ST a more reliable test in everyday practice. PMID- 17721284 TI - Merlin expression in secretory meningiomas: evidence of an NF2-independent pathogenesis? Immunohistochemical study. AB - One of the most common chromosomal regions implicated in the meningiomas tumorigenesis is 22q12 where the neurofibromatosis 2 (NF2) gene resides. The NF2 tumor-suppressor gene encodes for the merlin/schwannomin protein, which is responsible for the inherited disease neurofibromatosis 2. NF2 gene mutations predominantly occur in transitional and fibroblastic meningiomas, whereas the meningothelial variant is less affected. Secretory meningioma is an infrequent meningioma subtype. Its most typical morphologic feature is the presence of intracytoplasmic or extracytoplasmic round hyaline, eosinophilic, and periodic acid Shiff-positive bodies in a lesion frequently otherwise classifiable as meningothelial meningioma. This study reviews the immunohistochemical merlin expression in 14 consecutive secretory meningiomas. Our purpose was to investigate if secretory meningiomas, analogous to meningothelial meningiomas, follow a molecular route of pathogenesis independent of the neurorofibromatosis 2 gene-associated pathway. All meningiomas showed positive immunocoloration involving the majority of the hyaline inclusions and secretory cells; in 12 (86%) meningiomas, a positive immunoreaction was also documented in nonsecretory tumoral cells. Our results may indicate a molecular, besides morphologic, similarity between secretory and meningothelial meningiomas: the almost constant merlin immunohistochemical expression in our series gives evidence for a possible NF2 gene-independent pathogenesis in secretory meningiomas. PMID- 17721286 TI - Heritability of corneal curvature and astigmatism: a videokeratographic child parent comparison study. AB - PURPOSE: To study child-parent similarities and the heritability of corneal shape by applying a variance component model to videokeratographic data. METHODS: Sixteen astigmatic (keratometric cylinder >/= 1.0 D) and 18 nonastigmatic (keratometric cylinder < 1.0 D) children, 7-14 years of age (mean age, 9.5 years), were enrolled with their parents. Corneal curvature, corneal astigmatism (axis and magnitude), asphericity, corneal uniformity index, and Rabinowitz McDonnell inferior-superior dioptric asymmetry value (I-S value), as well as spherical and astigmatic topographic patterns, were determined by a corneal topographer. Child-parent comparisons were assessed through a 1-way analysis of variance and the chi test. For corneal curvature, corneal astigmatism, and asphericity, heritability was estimated by a variance component model after adjustments were made for age and sex. RESULTS: Both astigmatic and nonastigmatic children showed steeper keratometric values than their parents (P < 0.05). The axis values of corneal astigmatism showed no statistically significant difference (P = 0.684) between astigmatic offspring and their parents, whereas the magnitude values were significantly higher (P < 0.001) in astigmatic children. Altogether, 68% (95% confidence interval [CI], 66%-72%) of child-parent comparisons showed the same topographic pattern between parents and their offspring. Heritability values (48%; 95% CI, 36%-57%) were statistically significant for corneal curvature (P < 0.00001) and <30% for corneal astigmatism and asphericity. CONCLUSIONS: The application of a variance component model to videokeratographic child-parent comparisons suggests that the genetic contribution to corneal shape affects corneal curvature rather than corneal astigmatism. PMID- 17721287 TI - Candida interface keratitis after deep anterior lamellar keratoplasty: clinical, microbiologic, histopathologic, and confocal microscopic reports. AB - PURPOSE: To report the clinical, histopathologic, microbiologic, and confocal microscopic features of Candida keratitis after deep anterior lamellar keratoplasty (DALK). METHODS: We performed clinical, confocal scan, microbiologic and histopathologic examinations on two corneas from 2 young patients who underwent DALK for keratoconus. RESULTS: The first patient presented with asymptomatic white to cream-colored interface deposits 2 months after DALK. The confocal scan disclosed clusters of hyperreflective, fine granular deposits at the region of interface, with no evidence of inflammation or hyphaelike structures. The clinical presumption of possible "epithelial downgrowth" was suggested, and because of the progression of these lesions, irrigation of the interface was considered. Finally, penetrating keratoplasty was performed because of a rupture in the Descemet membrane. Histopathologic examination of the cornea disclosed yeastlike structures within the interface area. The microbiologic results of the irrigation fluid showed Candida glabrata. The second patient presented with a symptomatic infiltration of the inferior interface close to the suture site 2.5 months after DALK. The confocal scan showed foci of inflammation with clusters of hyperreflective round-shaped structures that resembled epithelial cells. Clinically, there was a suggestion of epithelial downgrowth, and subsequently, penetrating keratoplasty was performed because of the progression of the lesion. Histopathologic examination of the cornea disclosed an acute and chronic granulomatous keratitis caused by yeastlike structures. The microbiologic results revealed infection with Candida albicans. CONCLUSIONS: These are the first reported occurrences of interface Candida keratitis after DALK and with different confocal features. The clinical and the confocal features of interface Candida keratitis may be similar to those seen in epithelial downgrowth, which may postpone correct diagnosis and treatment. Candida keratitis should be considered in cases of interface deposits after any form of lamellar keratoplasty. PMID- 17721288 TI - Nearwork-induced changes in topography, aberrations, and thickness of the human cornea after interrupted reading. AB - PURPOSE: Recent experiments have suggested transient changes in corneal optics after short durations of reading. This study investigated an interrupted 1-hour period of reading on corneal topography in a sample of young myopic and emmetropic adults. METHODS: Ten myopic and 9 emmetropic young adult subjects were recruited for the study. They read adult-level text binocularly at 40 cm with approximately 30 degree downward gaze for 1 hour, with distance correction in place. Orbscan II corneal topography was performed at baseline and 5, 15, 30, and 60 minutes after reading during 1 test session to assess for changes in corneal power, aberrations, and thickness. RESULTS: Myopes exhibited greater corneal power and spherical aberration than emmetropes both before and after reading. Increased corneal higher-order aberrations (at baseline only) and thickness (superior position only) were observed in myopes versus emmetropes. CONCLUSIONS: Several corneal parameters differed in the myopes after reading as compared with emmetropes. Differences in corneal parameters were smaller in this study than found in earlier studies, perhaps because of the interrupted nature of the task in the former versus the continuous nature in the latter. PMID- 17721289 TI - Reliability of a video-based noncontact specular microscope for assessing the corneal endothelium. AB - PURPOSE: To assess the within- and between-examiner reliability of corneal endothelial cell density (ECD) measurements with 2 noncontact specular microscopes: a video-based system (SeaEagle) and a photographic system (Noncon Robo). METHODS: In 57 eyes of 57 subjects, 47 healthy subjects and 10 patients with corneal disease, ECD was measured in the center and at 4 paracentral areas with the video-based system (SeaEagle) and in the center with a photographic system (Noncon Robo). For the between-examiner reliability, a second examiner measured the central ECD with the SeaEagle device in 12 healthy subjects. The video-based system was also used to evaluate the agreement between the automated and the manually corrected (semiautomated) modes of repeated measurements. RESULTS: For central ECD in all eyes, the test-retest reliability assessed by the intraclass correlation coefficient was 0.77, 0.99, and 0.91 for the automated SeaEagle, semiautomated SeaEagle, and Noncon Robo, respectively. Correlation was poor to good between the 3 measurement methods (range, 0.61-0.84). For between examiner reliability, the upper (lower) limits of agreement were 200 (-384) and 149 (-92) cell/mm for the automated and semiautomated SeaEagle, respectively. CONCLUSIONS: The best reliability of repeated measurements was found for the semiautomated SeaEagle. However, the semiautomated method showed significantly higher ECD values than the Noncon Robo, and this difference was highly dependent on ECD. Thus, we suggest that these methods should not be used interchangeably. The fully automated mode may need a further refinement of the cell detection algorithm. PMID- 17721290 TI - Effect of prophylactic oral acyclovir after penetrating keratoplasty for herpes simplex keratitis. AB - PURPOSE: To determine the effect of routine use of prophylactic oral acyclovir after penetrating keratoplasty (PK) for herpes simplex virus (HSV) keratitis on recurrence, rejection, and graft failure rates. METHODS: Records from 70 consecutive patients who underwent PK for HSV keratitis at the W.K. Kellogg Eye Center between August 1, 1990, and December 31, 2000, were reviewed. Data collected included preoperative disease activity, duration, host vascularity, pre and postoperative vision, and antiviral use. Particular attention was given to all episodes of HSV recurrence, graft rejection, and failure. RESULTS: Fifty-six patients (80%) were treated with prophylactic oral acyclovir after surgery. This cohort experienced fewer episodes of rejection (P = 0.006) and better overall graft survival (P = 0.04) than those who were not treated with prophylactic oral antivirals. There was no statistically significant difference in recurrence-free survival between the 2 groups (P = 0.22). Cox regression analysis failed to identify any single variable as a statistically significant predictor of recurrence, rejection, or graft failure. CONCLUSIONS: Prophylactic oral acyclovir use after PK for HSV keratitis is associated with decreased episodes of rejection and improved graft survival. PMID- 17721291 TI - Subbasal nerve regeneration after penetrating keratoplasty. AB - PURPOSE: To evaluate subbasal nerve regeneration, corneal sensitivity, and tear film function after penetrating keratoplasty. METHODS: Twenty keratoplasty patients were assessed before and 1, 3, 6, and 12 months after penetrating keratoplasty by using noncontact corneal esthesiometry, tear breakup time measurement, the phenol red thread test, and confocal microscopy. Ten healthy control subjects were also assessed by using these techniques on 1 occasion. Subbasal nerve images were analyzed by using customized software to evaluate nerve regeneration. RESULTS: Before surgery, the subbasal nerve plexus could be imaged only in 11 patients because of the existence of pathology. Significant deficits in nerve morphology were apparent in these patients compared with control subjects. No subbasal nerves were detected over the 12-month postoperative period. Central corneal sensitivity decreased significantly after surgery and returned to near normal levels after 12 months. Tear breakup time was significantly shorter at 3 and 12 months after keratoplasty. There were no significant differences in the phenol red thread test results before and after surgery. CONCLUSIONS: There is no direct association between subbasal nerve fiber regeneration, central corneal sensitivity, and tear film stability and volume. The apparent recovery of corneal sensitivity to normal levels 12 months postoperatively, in the absence of clinically observable subbasal nerves, may be a methodologic phenomenon related to the inability of current-generation confocal microscopes to image fine regenerating nerves that mediate corneal sensibility. PMID- 17721292 TI - Keratoconjunctivitis sicca in juvenile rheumatoid arthritis. AB - PURPOSE: To compare the symptoms, signs, and results of objective tests for keratoconjunctivitis sicca (KCS) in patients with juvenile rheumatoid arthritis (JRA) and controls. METHODS: Sixty-four patients with JRA and 64 age- and sex matched controls were compared in terms of symptoms, signs, and results of objective tests for KCS. Relation between tear film breakup time (TBUT), Schirmer test results, and JRA-related variables such as age of onset, duration, and type of JRA; presence of antinuclear antibodies (ANAs); and history of uveitis were evaluated. Analysis of variance, multivariate regression analysis, Kruskall Wallis, Student t tests, and chi tests were used for statistical analysis. RESULTS: Twelve and a half percent of patients with JRA complained of dry eye symptoms compared with 1.5% of the controls (P = 0.031). Dry eye signs were detected in 10.9% of patients with JRA compared with 1.5% of controls (P = 0.038). TBUT and Schirmer test results were lower in the JRA group than in controls (P = 0.032 and P = 0.029, respectively). Seven patients (10.9%) had definite and 1 (1.5%) had probable diagnosis of KCS in the JRA group compared with no children in the control group (P = 0.034). Within the JRA group, Schirmer test and TBUT results were significantly lower in male patients and ones with longer duration of disease. CONCLUSIONS: The prevalence of symptoms, signs, and definite diagnosis of KCS is higher and basal tear secretion and tear film stability are lower in children with JRA than in controls. Among children with JRA, male sex and longer duration of disease are independent risk factors for having decreased basal tear secretion and tear film stability. PMID- 17721293 TI - Evaluation of the corneal topographic characteristics of keratoconus with orbscan II in patients with and without atopy. AB - PURPOSE: : To analyze the differences in corneal topography in keratoconus patients with and without atopy. METHODS: : In the Beyoglu Eye Research and Training Hospital Refractive Surgery Department, corneal examination with the Orbscan II device (Bausch & Lomb) was done to all patients between May and June 2004 who were diagnosed as keratoconus with corneal topography findings and who did not have any surgical procedure. The atopy grading was done according to the criteria of the UK Atopy Study Group (1994). Patients were divided into 2 groups according to the presence of atopy. The Orbscan findings of the 2 groups were compared. RESULTS: : Among 70 keratoconus patients, 33 patients had partial or full atopy. Sixty-six eyes of the 33 patients were classified as the atopic group, whereas 74 eyes of the remaining 37 patients were classified as the control group. The mean age of the patients was 27.7 +/- 9.5 years in the atopic group and 26.9 +/- 9.5 years in the control group. The central corneal thickness was 428.5 +/- 37.1 mum in the atopic group and 491.8 +/- 56.3 mum in the control group. There was a statistically significant difference between the mean central and thinnest corneal pachymetric readings, the distance of thinnest point to corneal center, anterior and posterior elevation values, distances of the anterior and posterior elevation to the central cornea, and irregularity indexes in the 2 groups (P < 0.05). CONCLUSIONS: : This study shows that corneal topographic and pachymetric characteristics of keratoconus may be different in atopic eyes from those in nonatopic eyes. Atopic keratoconus patients could possibly be evaluated as a separate entity in keratoconus disease. PMID- 17721294 TI - An evaluation of tear film breakup time extension and ocular protection index scores among three marketed lubricant eye drops. AB - PURPOSE: To report the performance of an artificial tear containing propylene glycol and polyethylene glycol as active demulcents with hydroxypropyl-guar as a gelling agent (Systane Lubricant Eye Drops; Alcon, Fort Worth, TX) and compare it with that of 2 artificial tears containing carboxymethylcellulose (Refresh Tears and Refresh Endura Lubricant Eye Drops; Allergan, Irvine, CA). METHODS: This was a single-center, 3-visit, randomized, double-masked crossover study that evaluated the effect of Systane versus Refresh Tears and Refresh Endura using tear film breakup time (TFBUT) and ocular protection index (OPI) in subjects with dry eye (n = 50). TFBUT values (5, 10, 15, 20, 30, 45, and 60 minutes after instillation) divided by interblink interval (IBI) yielded OPI scores. RESULTS: Systane significantly improved TFBUT at 5, 10, 15, 20, and 60 minutes versus Refresh Tears and at 5, 10, 15, 20, and 30 minutes versus Refresh Endura. Systane OPI scores were significantly higher than Refresh Tears at 15 and 30 minutes and than Refresh Endura at 5 minutes. CONCLUSIONS: This study suggests that Systane Lubricant Eye Drops was more effective than Refresh Tears at prolonging TFBUT up to 20 minutes after instillation and more effective than Refresh Endura at prolonging TFBUT up to 30 minutes after instillation. These data show that Systane is an effective first-line dry eye therapy and a superior ocular surface protector compared with Refresh Endura and Refresh Tears in the sample test population. PMID- 17721295 TI - Quality assessment and microbiologic screening of donor corneas. AB - PURPOSE: To identify possible predictors of donor corneal contamination. METHODS: Relationships between eye-banking characteristics of donor corneas and surgical corneoscleral rim culture results were examined in a retrospective case-control study by using logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Of 263 donor corneal rims, microbial recovery occurred from 23 (9%), including 6 yielding Clostridium perfringens. After adjusting for outdoor temperature and death-to-preservation duration, a positive rim culture occurred more often among tissues having an acceptable but less favorable biomicroscopic rating (OR, 4.22; 95% CI, 1.27-13.98). CONCLUSIONS: This exploratory study suggests that slit-lamp assessment of corneal appearance may correlate with subsequent microbiologic results. Ensuring optimal selection and preservation of the donor cornea may contribute to the safety of eye banking. PMID- 17721296 TI - Intacs for keratoconus and post-LASIK ectasia: mechanical versus femtosecond laser-assisted channel creation. AB - PURPOSE: To evaluate the efficacy of intracorneal ring segments to treat keratoconus and post-laser in situ keratomileusis (LASIK) keratectasia implanted by using either mechanical dissection or a femtosecond laser. METHODS: Thirty three eyes of 29 patients had intracorneal ring segments implanted by using mechanical dissection (17 eyes) or a femtosecond laser (16 eyes). Mean follow-up was 10.3 months. Parameters assessed before and after surgery included uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), manifest refractive spherical equivalent (MRSE), refractive cylinder (RC), best contact lens-corrected visual acuity (BCLVA), and contact lens tolerance. RESULTS: Statistically significant changes occurred for all parameters when we analyzed all 33 eyes as 1 group. Mean UCVA LogMar values improved from 1.0 +/- 0.3 (20/200) to 0.6 +/- 0.4 (20/80) (P < 0.0005). Mean BSCVA changed from 0.3 +/- 0.2 (20/40) to 0.2 +/- 0.2 (20/30) (10%; P < 0.05), and MRSE from -9 +/- 4 to -7 +/- 4 D (P < 0.05; 20%). There was a decrease of 0.5 D or more of RC in 62% of eyes. BCLVA improved from 0.2 +/- 0.2 (20/30) to 0.1 +/- 0.1 (20/25) after surgery (P < 0.02). Contact lens tolerance improved in 81% of eyes. There was no statistically significant difference in outcomes between mechanical dissection and femtosecond laser-assisted techniques. However, although statistical power was adequate to detect changes in clinical parameters as a result of surgery, it was not sufficient to conclusively show such differences between surgical techniques. CONCLUSIONS: For mild to moderate cases of keratoconus and post-LASIK keratectasia, the use of a femtosecond laser for Intacs channel creation seems as effective as mechanical dissection. Future studies are warranted to further evaluate channel creation by a femtosecond laser. PMID- 17721297 TI - Keratoconus is not associated with mutations in COL8A1 and COL8A2. AB - PURPOSE: To evaluate the suggested role of the COL8A1 and COL8A2 genes in the pathogenesis of the corneal ectatic disorders keratoconus and keratoglobus through mutation screening in affected patients. METHODS: DNA extraction, polymerase chain reaction amplification, and sequencing of COL8A1 and COL8A2 were performed in 50 unrelated keratoconus and 2 unrelated keratoglobus patients. RESULTS: No sequence variations were identified in COL8A1 and COL8A2 in the 2 patients with keratoglobus. Screening of COL8A1 in keratoconus patients revealed a previously identified single nucleotide polymorphism (SNP; c.1850C>T; Pro535Pro), in 1 patient. Screening of COL8A2 in keratoconus patients revealed 7 previously described SNPs: c.14G>A (Gly3Arg); c.112G>A (Ala35Ala); c.1012C>G (Leu335Leu); c.1308G>A (Arg434His); c.1492G>A (Gly495Gly); c.1512C>T (Thr502Met); and c.1765C>T (Pro586Pro). Four novel sequence variants were also identified, each in 1 affected patient: c.38_40dupCTG (Leu11dup), also identified in an unaffected relative of the affected proband, c.667G>A (Gly220Gly), c.1588G>A (Pro527Pro), and c.2026C>T (Val673Val). None of the 3 novel synonymous substitutions identified in COL8A2 was predicted to produce a splice acceptor site. CONCLUSIONS: The absence of pathogenic mutations in COL8A1 and COL8A2 in patients with keratoconus indicates that other genetic factors are involved in the pathogenesis of this corneal ectatic disorder. PMID- 17721298 TI - Corneal ulcers associated with aerosolized crack cocaine use. AB - PURPOSE: We report 4 cases of corneal ulcers associated with drug abuse. The pathogenesis of these ulcers and management of these patients are also reviewed. METHODS: Review of all cases of corneal ulcers associated with drug abuse seen at our institution from July 2006 to December 2006. RESULTS: Four patients with corneal ulcers associated with crack cocaine use were reviewed. All corneal ulcers were cultured, and the patients were admitted to the hospital for intensive topical antibiotic treatment. Each patient received comprehensive health care, including medical and substance abuse consultations. Streptococcal organisms were found in 3 cases and Capnocytophaga and Brevibacterium casei in 1 patient. The infections responded to antibiotic treatment. Two patients needed a lateral tarsorrhaphy for persistent epithelial defects. CONCLUSIONS: Aerosolized crack cocaine use can be associated with the development of corneal ulcers. Drug abuse provides additional challenges for management. Not only treatment of their infections but also the overall poor health of the patients and increased risk of noncompliance need to be addressed. Comprehensive care may provide the patient the opportunity to discontinue their substance abuse, improve their overall health, and prevent future corneal complications. PMID- 17721299 TI - A protein dye-binding assay on cellulose membranes for tear protein quantification: use of conventional schirmer strips. AB - PURPOSE: To develop a method to quantify tear protein concentration with the sensitivity to measure this variable in the restricted volumes of single human tear samples. METHODS: Aliquots of tear fluid from healthy subjects and a solution of standard bovine serum albumin (BSA) were spotted on cellulose membranes. Membranes were fixed, stained for protein with Coomassie blue, and washed until they displayed clear backgrounds. Stained spots were excised and eluted in a defined volume of methanol-ammonia, and the absorbance was determined spectrophotometrically at 610 nm. Membranes were calibrated by calculating their apparent thickness from the areas of stained spots and the corresponding aliquot volumes of either tear fluid or BSA solution. RESULTS: In our dye-binding assay, absorbance (0-1.00 OD) was found to have a linear relation with tear fluid volume (1-7 microL). In a study involving samples from 33 healthy subjects, aliquots (3 microL) of tear fluid were found to yield absorbances in the linear range. Protein concentrations in tear fluid were found to be distributed over the range of 2.20-6.37 mg/mL (mean, 4.11 +/- 1.00 mg/mL) with no apparent sex differences. The assay can be applied successfully to quantify protein concentrations in tear fluid by using calibrated Schirmer strips after a tear test. Electrophoretic profiles of proteins present in tear fluid sampled from different healthy individuals were nearly identical when normalized for protein load by using this method. CONCLUSIONS: The protein dye-binding assay we developed by using cellulose membranes or Schirmer strips is an efficient and convenient method for measuring tear protein concentration. PMID- 17721301 TI - Immunohistochemical evaluation of two corneal buttons with post-LASIK keratectasia. AB - PURPOSE: To examine immunohistochemically 2 human corneal buttons after corneal transplantation for post-laser in situ keratomileusis (LASIK) keratectasia. METHODS: Two ectatic corneas after penetrating keratoplasty and 2 postmortem control corneas from a patient after uncomplicated LASIK were used. Cryostat sections were stained by immunofluorescence for >30 extracellular matrix (ECM) components and proteinases. RESULTS: The ratios of distance between LASIK flap interface and the upper epithelial layer to total corneal thickness were 0.27 0.34 in all cases. The whole flap interface was positive only for total and cellular fibronectin. Stromal types VI and XIV collagen, fibrillin-1, tenascin-C, and vitronectin were unchanged with no evidence of fibrosis. In ectasia cases, keratocytes adjacent to the flap did not express nidogens. Staining for type IV collagen alpha5 chain, nidogen-2, chains of laminin-8, and laminin-10 was weak and discontinuous in the epithelial basement membrane (EBM). Type IV collagen alpha1/alpha2 chains were found in the EBM of ectasia cases only. Matrix metalloproteinase (MMP)-10 showed increase in the epithelium, and MMP-3, in some keratocytes near the flap interface of ectatic corneas. Also, cathepsin F was seen at the flap margin only. Staining for limbal basal epithelial marker, alpha enolase, was mostly absent in the ectatic cases, suggesting largely normal epithelial differentiation. CONCLUSIONS: Abnormal EBM structure similar to that previously observed in keratoconus and bullous keratopathy and an increase in certain proteinases suggest ongoing EBM lysis and remodeling. Immunohistochemical staining for fibronectin may be used to reveal the position of flap interface. PMID- 17721300 TI - Safety profile of bevacizumab on cultured human corneal cells. AB - PURPOSE: To study the corneal biocompatibility of bevacizumab on various cultured human corneal cells. METHODS: Cell cultures of corneal keratinocytes (CKs), corneal fibroblasts (CFs), and corneal endothelial cells (CECs) were harvested from human donor eyes and exposed to various concentrations of bevacizumab (0.25 5.0 mg/mL). Cell viability was assessed by using the 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay at days 1 and 4 after exposure. For cytotoxicity testing, confluent cells were cultured in serum-depleted medium, and the MTT test was performed after 24 hours of incubation. Expression of vascular endothelial growth factor (VEGF), VEGF receptors (VEGFR1 and VEGFR2), keratan sulphate (KS), and cytokeratin-3 (AE5) was studied by immunohistochemistry. Live/dead viability/cytotoxicity assay was performed and analyzed by fluorescence microscopy after 24 hours of incubation. Cell morphology was assessed with a phase-contrast microscope after 7 days of exposure with different concentrations of bevacizumab (0.25-5.0 mg/mL), and signs of cellular damage were assessed. RESULTS: No cytotoxic effect of bevacizumab on CKs, CFs, and CECs could be observed when used at a concentration of 5.0 mg/mL or lower. Bevacizumab-treated cells showed no signs of cellular damage compared with the control. CKs, CFs, and CECs stained positively for VEGF, VEGFR1, and VEGFR2. CKs and CECs stained positively for AE5, whereas CFs were immunopositive for KS. CONCLUSIONS: Bevacizumab is not toxic to corneal cells of human origin in vitro at doses usually used for treatment of corneal neovascularization, which is 20-fold higher than that used for intravitreal application. PMID- 17721302 TI - Secondary amyloidosis in the hydrops lesion of a patient with pellucid marginal degeneration. AB - PURPOSE: To report a case of secondary corneal amyloidosis in a chronic hydrops lesion of a patient with pellucid marginal degeneration (PMD). METHODS: Clinicopathologic case report with a review of the literature. A 63-year-old man with PMD developed acute hydrops in 1999, which never resolved and became an elevated, gelatinous lesion with peripheral neovascularization. Penetrating keratoplasty was performed in 2005, and the excised button was examined histopathologically. RESULTS: The excised button revealed substantial subepithelial acellular deposits consistent with amyloid in the area of the unresolved gelatinous lesion, overlying a disruption in Descemet membrane, confirming the diagnosis of secondary corneal amyloidosis. CONCLUSIONS: Secondary corneal amyloidosis is a corneal response to chronic injury and irritation that is not commonly reported and often overlooked. To the best of our knowledge, this is the first report of a dramatic secondary amyloidosis deposit in the chronic hydrops lesion of a patient with PMD. PMID- 17721303 TI - Keratomalacia caused by psychiatric-induced dietary restrictions. AB - PURPOSE: To describe the unique presentation, clinical course, management, and outcome of vitamin A deficiency-induced keratomalacia leading to bilateral corneal melts and ulcers in a patient with severe dietary restrictions because of psychiatric disease. METHODS: Review of patient's record and literature pertinent to her condition. RESULTS: A 33-year-old woman with a phobia of consuming most foods presented with bilateral corneal ulcers and melts from an unusual case of keratomalacia caused by vitamin A deficiency. The disease process progressed to bilateral perforations necessitating emergent bilateral penetrating keratoplasties. Pathologic examination confirmed classic signs of xerosis and keratomalacia. To our knowledge, our case is unique in that it is the only one in which the histopathology of the corneal lesion is described. CONCLUSIONS: Psychiatric diseases, particularly eating disorders limiting sufficient nutrient intake, can lead to severe ocular surface disease that can be both vision- and life threatening. PMID- 17721304 TI - Long-term sequelae of isolated chemical "airbag" keratitis. AB - PURPOSE: To report the long-term sequelae of a case of bilateral chemical keratitis caused by airbag deployment. METHODS: Case report and review of the literature. RESULTS: A 21-year-old woman presented with bilateral reduced vision, photophobia, and tearing after a car accident. Examination revealed some facial burns and severe chemical injury to the cornea and conjunctiva. Immediate irrigation with physiologic saline solution and subsequent treatment with topical antibiotics, corticosteroids, and vitamin C resulted in full restoration of vision but could not prevent permanent corneal damage. CONCLUSIONS: Severe alkali injury of the cornea generally has a good prognosis but can lead to permanent damage and persistent complaints of dry eye. PMID- 17721305 TI - A case of herpetic keratitis after intravitreal triamcinolone injection. AB - PURPOSE: We report a case of herpetic epithelial keratitis that developed after intravitreal triamcinolone acetonide injection. METHODS: An 81-year-old man with diabetes with severe nonproliferative diabetic retinopathy and diffuse macular edema in both eyes received bilateral intravitreal injections of 0.4 mg/0.1 mL of triamcinolone acetonide. RESULTS: Eighteen days after the injections, the patient presented with redness, tearing, foreign body sensation, and decreased visual acuity in the right eye. The cornea showed dendriform ulcers that exhibited positive fluorescein staining. Diagnosis for herpes simplex epithelial keratitis was made, and topical acyclovir ointment therapy was initiated. The epithelial lesions healed after 7 days of therapy. CONCLUSIONS: Herpes simplex epithelial keratitis can be a possible complication of intravitreal triamcinolone acetonide injection. The course and response to conventional therapy was no different from that of the classical course of the disease. PMID- 17721306 TI - Case of corneal melting associated with the use of topical nepafenac. AB - PURPOSE: To report a case of corneal melting associated with the use of the topical nonsteroidal anti-inflammatory agent Nepafenac. METHODS: Case report and literature review. RESULTS: A 62-year-old woman with a complicated ocular history developed corneal melting associated with the use of Nepafenac. On discontinuation of Nepafenac, the melt rapidly resolved. CONCLUSIONS: Topical nonsteroidal anti-inflammatory agents have been associated with corneal ulceration and stromal melts. This is, to our knowledge, the first reported case involving the new agent, Nepafenac. PMID- 17721307 TI - Clinicopathologic correlation of explanted AlphaCor artificial cornea after exposure of implant. AB - PURPOSE: To describe the clinical presentation and histopathologic findings in a case of explantation of an AlphaCor artificial cornea implant caused by exposure of the skirt. METHODS: We describe the case report of a 46-year-old man who suffered trauma to the right eye, resulting in 4 failed penetrating keratoplasties (PKPs). Subsequently, an AlphaCor implantation was performed with some visual improvement. Slightly more than 2 years after the implant, skirt exposure occurred, possibly secondary to infectious keratitis in an area of a ruptured bulla, and explantation was performed. Corneal stability was established with repeat corneal transplantation. RESULTS: Histopathologic evaluation of the surgical specimen revealed chronic nongranulomatous inflammation and fibrosis in the peripheral skirt, indicating that biointegration was maintained. However, peripheral corneal stromal melting led to skirt exposure. Focal calcification, as well as retroprosthetic membrane formation, was also identified. CONCLUSIONS: The AlphaCor implant is a viable method of treatment for multiple failed PKPs, but it may be associated with unique complications, including corneal stromal melting, focal calcification, and retroprosthetic membrane formation. Infectious keratitis may be a risk factor for corneal stromal melting and needs to be managed aggressively. Explantation of the implant is essential if the skirt is exposed. PMID- 17721308 TI - Recalcitrant Beauveria bassiana keratitis: confocal microscopy findings and treatment with posaconazole (Noxafil). AB - PURPOSE: To report the clinical, confocal microscopic, and histologic appearance of a case of Beauveria bassiana keratitis and response to medical therapy. METHODS: A 58-year-old woman with a 1-month history of a recalcitrant contact lens-related corneal ulcer was evaluated by confocal microscopy and corneal scraping for histology and culture. RESULTS: Confocal microscopy and histology revealed a filamentous fungal keratitis confirmed by culture as B. bassiana resistant to amphotericin B. The keratitis was unresponsive to multiple topical and systemic antifungals but resolved after the addition of oral posaconazole. CONCLUSIONS: B. bassiana is a rare cause of keratitis that may show significant resistance to topical and systemic antifungals but was treated successfully with the addition of oral posaconazole to topical voriconazole. Confocal microscopy and corneal smears may be of benefit in identifying and directing therapy for this slow-growing fungus. PMID- 17721309 TI - Infectious crystalline keratopathy caused by Serratia marcescens. AB - PURPOSE: To report the case of a 70-year-old woman with Serratia infectious crystalline keratopathy. METHODS: Case report. RESULTS: This is a report of a 70 year-old woman with a history of chronic open-angle glaucoma and trachoma with lagophthalmos, entropion, and trichiasis in both eyes who developed crystalline keratopathy after penetrating keratoplasty and cataract extraction in the right eye followed up with treatment with long-term topical steroids. Ten months after the initial penetrating keratoplasty and cataract extraction, the patient had decreased visual acuity, intense pain, and tearing in the right eye. Corneal cultures showed Serratia marcescens. Topical steroids were discontinued, and treatment with tobramycin and vancomycin ophthalmic solution every hour was initiated. Despite 1 week of aggressive therapy, there was an increase in corneal infiltrate, epithelial defects, and melting, which eventually involved the peripheral recipient cornea. Therapeutic penetrating keratoplasty, debridement of the peripheral cornea, and amniotic membrane transplantation were performed. Antibiotic agents were used postoperatively. There has been no evidence of recurrent infection. The best-corrected visual acuity improved to 6/15 at the 6 month follow-up period after the second intervention. CONCLUSIONS: S. marcescens may cause infectious crystalline keratopathy after penetrating keratoplasty in patients treated with long-term topical steroids. Therapeutic penetrating keratoplasty, surgical debridement, and amniotic membrane transplantation may be necessary when the clinical response to intensive medical treatment is inadequate. PMID- 17721310 TI - Invasive spindle cell carcinoma of the conjunctiva managed by full-thickness eye wall resection. AB - PURPOSE: To describe an invasive spindle cell carcinoma of the conjunctiva managed by full-thickness eye wall resection. METHODS: A 51-year-old man developed a conjunctival mass that was excised and proved to be a spindle cell carcinoma. A tumor recurrence 20 months later was evaluated by ultrasound biomicroscopy (UBM) and managed by full-thickness eye wall resection and scleral graft. RESULTS: UBM depicted an epibulbar mass with deep invasion through the limbus to Descemet membrane. The tumor was removed by full-thickness eye wall resection and scleral graft. CONCLUSIONS: Deep scleral invasion of conjunctival spindle cell carcinoma can sometimes be managed by local resection rather than irradiation or enucleation. PMID- 17721311 TI - A missense mutation in the M1S1 gene found in a turkish patient with gelatinous droplike corneal dystrophy. AB - PURPOSE: To report a missense mutation in the M1S1 gene found in a Turkish patient with gelatinous droplike corneal dystrophy (GDLD). METHODS: A Turkish patient with GDLD was examined. Keratoplasty was performed and a diagnosis of GDLD was made by histopathologic and electron microscopic studies. Genomic DNA was extracted from peripheral blood and the paraffin-embedded tissue of the corneal button. A 248-bp DNA fragment of the M1S1 gene was amplified, and sequencing reactions were analyzed. The results were compared with those of 30 healthy, nonrelated individuals. RESULTS: On light microscopic examination, sheets of amorphous amyloid deposits were observed in subepithelial regions and in the anterior and midcorneal stroma. Electron microscopy revealed dense collagen fibrils and entrapped filamentous amyloid fibrils in the corneal stroma. A substitution of T-->C at nucleotide 557 was found in the peripheral blood DNA sequence analysis, which resulted in an amino acid substitution of L-->P (L186P). Results were confirmed by direct DNA sequencing analysis of the paraffin-embedded corneal button. The patient with GDLD was homozygous for the mutation, resulting in amino acid substitution L186P. CONCLUSIONS: This is the first report, to our knowledge, of a homozygous mutation (L186P) in the M1S1 gene found in a Turkish patient. The clinical examination may be insufficient in sporadic cases, and histopathologic examination and molecular genetic analysis can accelerate and improve the accuracy of diagnosis in patients with GDLD. PMID- 17721312 TI - Deep lamellar keratoplasty for acanthamoeba keratitis. AB - PURPOSE: To describe deep lamellar keratoplasty (DALK) as a surgical alternative to penetrating keratoplasty in the management of unresponsive Acanthamoeba keratitis. METHODS: Interventional case report. We performed DALK in a patient with Acanthamoeba keratitis unresponsive to intensive antimicrobial therapy. A modified form of the Anwar big-bubble technique, with total corneal stromal removal down to Descemet membrane, was successfully performed without entry into the anterior chamber. Subsequent delay in graft epithelialization relating to ocular surface toxicity from prolonged antiacanthamoebal topical therapy required a secondary amniotic membrane patch graft. RESULTS: No recurrence of Acanthamoeba infection occurred after surgery. Reepithelialization after the amniotic membrane patch graft was successful, and full visual recovery occurred, resulting in a best-corrected visual acuity of 20/20. CONCLUSIONS: DALK with total removal of infected stromal tissue may be performed in medically unresponsive cases of Acanthamoeba keratitis, which ordinarily may require penetrating keratoplasty. Advantages of DALK in infectious keratitis include less risk of intraocular entry of infectious organisms at the time of surgery and the potential for improved graft survival rates caused by less endothelial rejection and failure. PMID- 17721313 TI - Tear film normalization test. PMID- 17721315 TI - Posterior lamellar keratoplasty. PMID- 17721317 TI - Deep anterior lamellar keratoplasty for keratoconus. PMID- 17721319 TI - Resolution of equivocal results with the Hybrid Capture II high-risk HPV DNA test: a cytologic/histologic review of 191 cases. AB - INTRODUCTION: The Hybrid Capture II (HC II, Digene) high-risk human papilloma virus (HPV) (hrHPV) DNA test is an in vitro nucleic acid hybridization assay that uses enhanced chemiluminescence for the qualitative and semiquantitative detection of hrHPV in cervical samples. Patient samples are concomitantly tested with positive and negative DNA controls and results reported as positive or negative on the basis of a ratio of relative light units to a cutoff value derived from the positive control (RLU/CO). Samples with a ratio <1.0 RLU/CO are expressed as negative for hrHPV, samples with a ratio >2.5 RLU/CO are expressed as positive for hrHPV, and samples with a ratio between these numbers are submitted for retesting. These "equivocal" values are resulted as positive for hrHPV if either of 2 subsequent test values equals or exceeds 1.0 RLU/CO. Samples that show <1.0 RLU/CO after 2 repeat tests are resulted as negative for hrHPV. METHODS: In this study, we evaluated all hrHPV test results over a 17-month period in our institution. Initial tests showing an equivocal result were analyzed for final retesting result, and for all corresponding and subsequent cytology and histology results. All hrHPV tests were conducted on SurePath (TriPath) or ThinPrep (Cytyc) cervical cytology specimens using the HC II hrHPV DNA test. Subsequent hrHPV tests also were correlated with incident and follow-up findings. RESULTS: A total of 4792 hrHPV test results were evaluated. Of these, 191 (4%) showed equivocal initial results. When retested, 178 of the 191 samples (93%) resulted positive for hrHPV on first retest and an additional 8 resulted positive for hrHPV on the second retest, bringing the total positive tests to 186 out of 191 (97.4%). Five samples (2.6%) out of 191 were finally expressed as negative for hrHPV. Corresponding cytologic interpretations for the 191 specimens were as follows: NILM-30, atypical squamous cell of undetermined significance (ASC-US)-138, atypical squamous cells--cannot exclude HSIL-13 (ASC-H-13), LSIL-9, and high-grade squamous intraepithelial lesion (HSIL)-1. Follow-up histology was available for 60 of the 191 equivocal cases and showed cervical intraepithelial neoplasia (CIN) II or CIN III in 7 cases, CIN I in 13 cases, and negative or reactive changes in 40 cases. CONCLUSIONS: On the basis of the results, repeat testing of equivocal specimens might not be necessary as these specimens are overwhelmingly found to be positive for hrHPV. Additionally, hrHPV tests falling in the equivocal range should be considered as definite positive tests, as follow up results in this cohort demonstrate that significant histologic abnormalities are associated with 10.5% of these cases (20/191), and with 33% of those biopsied (20/60) cases. PMID- 17721320 TI - Measurement of signaling pathway activities in solid tumor fine-needle biopsies by slide-based cytometry. AB - The application of molecular targeted therapies is expected to cause a modulation of cellular signaling pathway(s) that can be monitored by sequential biopsies. Fine-needle sampling (FNS) is an atraumatic and safe technique that can be repeated at numerous points during the clinical or experimental administration of a drug. However, small volume and paucicellularity of fine-needle samples may preclude a comprehensive analysis. We describe here the image-based detection of phosphorylated signaling proteins, an approach for the measurement of pathway activities and preliminary concepts for a multiplexed analysis in these specimens. Fine-needle samples were obtained from xenograft tumors and used for cell block preparations. Preanalytical parameters for the detection of phosphorylated Stat3 and nuclear factor kappaB were determined. A cytometric approach for the measurement of pathway activities was tested using 2 different slide-based analysis techniques applied to immunofluorescence and immunohistochemistry. Changes in the phosphorylation state of Stat3 and nuclear factor kappaB were observed due to delayed fixation and reproducibly quantified. Data obtained from xenografts after drug treatment suggest that slide-based cytometry gives results that are comparable to conventional analysis methods. The applicability of quantum dot nanocrystals for the detection of phosphorylated Stat3 and the combination of different labeling techniques suggest a potential for a multiplexed analysis. We propose here that FNS of solid tumors may be useful in anatomic sites where core-needle biopsies are not possible or not well tolerated. FNS can be used for biomarkers with a homogeneous distribution throughout the tumor, and slide-based analysis techniques may be applied to quantify pathway activities. PMID- 17721321 TI - Multiple molecular analyses from minimal cell quantities by sequential isolation and preamplification of DNA and RNA. AB - Molecular analyses of single or very few cells are often handicapped by low amounts of DNA or RNA from starting material. Specimens like biopsies, embryonic stem cells, or laser-microdissected tissues often do not provide nucleic acid quantities required for robust amplification and verification by diagnostic polymerase chain reaction (PCR)-based analyses. A simultaneous isolation procedure for both RNA and DNA from a single sample would greatly facilitate demanding molecular studies. Here, we describe a new method that combines the isolation of mRNA using commercially available oligo (dT)-bound magnetic beads with the precipitation of DNA from the remaining cell lysate. Both types of nucleic acids can then be separately preamplified by improved primer extension preamplification and subsequently used for multiple molecular analyses. With this procedure we were able to reliably gain DNA for PCR from as few as 5 cells. RNA suitable for various reverse transcription-PCR approaches and sequencing analyses could simultaneously be isolated even from single cell preparations. PMID- 17721323 TI - High preservation of DNA standards diluted in 50% glycerol. AB - Standard curves are important tools in real-time quantitative polymerase chain reaction (PCR) to precisely analyze gene expression patterns under physiologic and pathologic conditions. Handling of DNA standards often implies multiple cycles of freezing and thawing that might affect DNA stability and integrity. This in turn might influence the reliability and reproducibility of quantitative measurements in real-time PCR assays. In this study, 3 DNA standards such as murine tumor necrosis factor (TNF) alpha, interferon (IFN) gamma, and kainat-1 receptor were diluted in 50% glycerol or water after 1, 4, and 16 cycles of freezing and thawing and amplified copy numbers after real-time PCR were compared. The standards diluted in water showed a reduction to 83%, 55%, and 50% after 4 cycles, to 24%, 5%, and 4% after 16 cycles for kainat-1 receptor, TNFalpha, and IFNgamma standards, respectively, when compared with a single cycle of freezing and thawing. Interestingly, all cDNA samples diluted in 50% glycerol were amplified in comparable copy numbers even after 16 cycles of freezing and thawing. The effect of the standards undergoing different cycles of freezing and thawing on sample values was demonstrated by amplifying cDNA obtained from Borna disease virus infected and noninfected TNF-transgenic mice brain. This revealed significant differences of measured cDNA copy numbers using water-diluted DNA standards. In contrast, sample values did not vary using glycerol-diluted standards that were frozen and thawed for 16 times. In conclusion, glycerol storage of DNA standards represents a suitable tool for the accurate and reproducible quantification of cDNA samples in real-time PCR analysis. PMID- 17721322 TI - A ribonuclease protection assay-based approach for analysis of angiogenic gene expression in archival tissues. AB - Archival, formalin-fixed and paraffin-embedded tissues routinely stored in pathology departments represent an invaluable resource for retrospective molecular biology studies for diagnostic and prognostic purposes. In such specimens extraction of transcriptionally competent RNA to be analyzed by conventional techniques, such as reverse transcription-polymerase chain reaction, is a challenging task. Therefore, we developed a novel methodological approach that allows successful detection and semiquantitative analysis of specific mRNAs obtained from archival formalin-fixed, paraffin-embedded specimens by ribonuclease protection assay. Specifically, we measured a panel of 7 angiogenic markers in selected archival tissues stored at room temperature and retrieved over a wide time span (10 y). The study series consisted in samples of benign and malignant melanocytic lesions. In our model, expression of FLT-1, the vascular endothelial growth factor receptor-1, correlated with the expression of mRNAs encoding other tyrosine kinase receptors, such as TIE-1 and TIE-2, as well as with angiopoietin and with the protease-activated receptor-1 and vascular endothelial growth factor itself. Relative to control (normal skin), in melanoma the expression of the selected angiogenic markers was significantly higher. In conclusion, our study provides evidence that ribonuclease protection assay on archival specimens would be highly valuable for retrospective studies, for diagnosis or prognosis. PMID- 17721324 TI - Gene expression profiling of Epstein-Barr virus-positive and -negative monomorphic B-cell posttransplant lymphoproliferative disorders. AB - Although most posttransplant lymphoproliferative disorders (PTLD) are related to Epstein-Barr virus (EBV) infection, approximately 20% lack detectable EBV (EBV-). It is uncertain whether the latter cases are truly distinct from EBV+ PTLD or possibly relate to another infectious agent. This study used gene expression profiling to further investigate the relationship between EBV+ and EBV- monomorphic B-cell PTLD, and to search for clues to their pathogenesis. Affymetrix HU133A GeneChips were used to compare 4 EBV+ and 4 EBV- cases of monomorphic B-cell PTLD. Hierarchical clustering successfully distinguished the EBV+ and EBV- groups. Relative to EBV- PTLD, 54 transcripts were over-expressed in EBV+ PTLD. The transcripts identified included IRF7 (a known regulator of EBV LMP1 expression), EBI2 (EBV-induced gene 2), and 3 that are interferon induced (MX1, IFITM1, and IFITM3). In addition, the EBV+ group contained 232 transcripts decreased relative to the EBV- group, including changes concordant with those previously reported after EBV infection of cultured B-cell lines. In summary, in a small group of monomorphic B-cell PTLD, EBV+ cases demonstrated a subset of gene expression changes associated with EBV infection of B cells. By contrast, EBV- PTLD lacked viral-associated changes suggesting that they are biologically distinct. PMID- 17721325 TI - Use of the real-time PCR assay in conjunction with MagNA Pure for the detection of mycobacterial DNA from fixed specimens. AB - Tuberculosis in immunocompromised patients is often caused by Mycobacterial species other than Mycobacterium tuberculosis. Thus, detection of and differentiation between M. tuberculosis and nontuberculosis species is necessary for diagnosis of disease in these patients. Furthermore, when tissue changes show granulomatous inflammation, quick confirmation testing for mycobacterial infection is needed for conclusive diagnosis. The aim of this study was to validate the utility of a real-time polymerase chain reaction (PCR) assay in conjunction with the MagNA Pure LC automated extraction system for the detection of mycobacterial DNA from formalin-fixed, paraffin-embedded specimens. A total of 46 archived, paraffin-embedded, fixed specimens showing granulomatous inflammation were studied for mycobacterial infection by real-time PCR. Bacterial DNA was extracted and isolated using the MagNA Pure extraction system. Real-time PCR was performed on the LightCycler using the Artus Real Art Mycob Diff ASR kit from Qiagen. Thirteen of the 46 patient specimens were positive for mycobacterial infection by acid-fast bacilli (AFB) stain. Of the13 reported positive by AFB stain, 12 where positive by real-time PCR. All 13 specimens reported positive by AFB were sent for culture confirmation. Eleven of 13 were returned positive by culture. Specimens reported as negative by culture and positive by real-time PCR were confirmed positive by a second PCR method from another reference laboratory. We believe that these studies are beneficial in the differential diagnosis of mycobacterial infection from fixed tissue specimens where tuberculosis might not have been clinically initially suspected and when specimens are not suitable for microbiologic examination. PMID- 17721326 TI - Microsatellite analysis in serum DNA as a diagnostic tool for distinction of patients with unknown pancreatic masses. AB - The clinical distinction between cancer and chronic pancreatitis is difficult in patients with pancreatic masses. To test whether detection of aberrant serum DNA could assist in this important differential diagnosis, we tested a panel of 12 microsatellitemarkers from chromosomes 17p, 17q, 13q, 9p, 5q, and 2p in the blood of 35 pancreatic cancer patients, 22 patients with chronic pancreatitis, and 20 healthy individuals. An average of 2.8 loss of heterozygosity (LOH) was found in 32 of 35 cancer patients of whom 30 (86%) had 2 or more LOH. LOH was also found in 7 of 22 pancreatitis patients but all these patients had only 1 LOH. No LOH was detected in healthy donors of comparable age. These data suggest that LOH analysis may be a substantial help for diagnosing pancreatic masses. An extension of the panel, perhaps in combination with a better selection of markers may further improve this assay. PMID- 17721327 TI - A novel variant of SYT-SSX1 fusion gene in a case of spindle cell synovial sarcoma. AB - Synovial sarcoma (SS) is a rare soft-tissue tumor that affects children and young adults. It is characterized by chromosomal translocation t(X;18)(p11.2;q11.2), which results in the fusion of the gene SYT on chromosome 18 with SSX genes on chromosome X. Heterogeneity within SS fusion junctions is rare. We report a case of a 9-year-old boy with a high-grade spindle cell sarcoma. Reverse transcriptase polymerase chain reaction revealed a characteristic translocation of SSs. However, this sarcoma showed a longer-than-expected PCR product after gel electrophoresis. Direct sequencing of the product disclosed a novel SYT/SSX1 fusion transcript. Detection of fusion transcripts is useful for diagnostics of SS. In each case, when considering this diagnosis on the morphologic grounds an attempt to analyze the translocation using PCR should be made, including the recognition of its uncommon variants. PMID- 17721328 TI - CYP2C9 and VKORC1 genetic polymorphism analysis might be necessary in patients with Factor V Leiden and prothrombin gene G2021A mutation(s). AB - The annual incidence of venous thromboembolism is approximately 117 per 100,000 persons or about 1 per 1000 person-years, with the majority of the disease occurring in the older age groups. Factor V Leiden gene (most common) and the prothrombin G20210A gene mutation are inherited mild to moderate risk factors for hypercoagulability. The anticoagulant warfarin requires close monitoring of the patient's prothrombin time, normalized as the international normalization ratio. Patients with either Cytochrome P-450 CYP2C9*2, CYP2C9*3, or VKORC1*2 genotype (c.-1639G>A) require significantly reduced doses, and are at a higher risk of serious bleeding. Thirty-five samples in total, 15 with Factor V Leiden, 18 with prothrombin G2021A mutation, and 2 with both were analyzed for 2C9*2, 2C9*3, and VKORC1 (-1639) allele variants by using the Invader CYP2C9 and VKORC1 polymorphism analysis kit. Eight with CYP2C9*2 C/T, 2 with CYP2C9*3 A/C, 5 with VKORC1 (-1639) A/A, and 22 with VKORC1 (-1639) G/A genotypes or 29 out of 35 (83%) samples analyzed were found with CYP2C9*2 C/T, CYP2C9*3 A/C, VKORC1 (-1639) G/A, or/and VKORC1 (-1639) A/A genotypes. CYP2C9*2 C/T, CYP2C9*3 A/C, VKORC1 ( 1639) G/A genotyping might be necessary for patients with Factor V Leiden and/or prothrombin G2021A mutation before warfarin anticoagulant therapy. PMID- 17721329 TI - Thoracic manifestations of immune restoration syndromes in AIDS. AB - Immune restoration syndromes (IRS) in AIDS constitute a group of illness characterized by a pathologic inflammatory response in patients with late-stage AIDS who start highly active antiretroviral therapy. Although there is no standardized definition or therapy, IRS have partial immune restoration associated with an increase in their CD-4 cell count and a decrease in their viral load. Patients with IRS show a paradoxical reaction that is, clinical worsening rather than improvement on therapy, associated with a recognized or occult infection. Symptoms include new or worsening fever, lymphadenopathy, pulmonary, visceral, central nervous system, or cutaneous disease which may be severe and occasionally life threatening and must be differentiated from disease progression. In this paper, we review the clinical and associated thoracic imaging findings of IRS associated with specific infections including mycobacterial and fungal infections, cytomegalovirus, Pneumocystis jiroveci pneumonia and also Kaposi sarcoma and sarcoidosis. Recognition of the imaging findings in the appropriate clinical setting presents an opportunity to make a timely diagnosis. With appropriate management, IRS usually does not alter long term prognosis. PMID- 17721330 TI - Acute exacerbation of chronic interstitial pneumonia: high-resolution computed tomography and pathologic findings. AB - PURPOSE: To review the high-resolution computed tomography (CT) and histologic findings of acute exacerbation of chronic interstitial pneumonia and to assess the potential value of CT and histologic findings in predicting prognosis. MATERIALS AND METHODS: The study included 24 patients with clinical and histologic diagnosis of acute exacerbation of chronic interstitial pneumonia who underwent CT within 1 month before biopsy or autopsy. The final diagnosis was acute exacerbation of idiopathic pulmonary fibrosis (n=12), usual interstitial pneumonia associated with connective tissue disorders (n=5), idiopathic nonspecific interstitial pneumonia (n=4), and nonspecific interstitial pneumonia associated with connective tissue disorders (n=3). RESULTS: The main CT findings consisted of bilateral ground-glass opacities (100%) and consolidation (71%) superimposed on a reticular pattern. The ground-glass opacities and/or consolidation were diffuse in 54% of the cases, multifocal in 21%, and peripheral in 25%. The histologic patterns of acute injury consisted of diffuse alveolar damage (n=20), acute organizing pneumonia (OP) (n=3), and extensive fibroblastic foci (n=1). Eight (33%) patients survived the acute episode, including all 3 patients with OP and the patient with extensive fibroblastic foci (P=0.01). The survivors included 3 of 13 (23%) patients with diffuse parenchymal opacification, 2 of 5 (40%) patients with multifocal, and 3 of 6 (50%) patients with peripheral opacification on CT. CONCLUSIONS: The CT findings of acute exacerbation of chronic interstitial pneumonia consist of diffuse, multifocal, or peripheral parenchymal opacification superimposed on reticulation. Histologic findings of OP are superior to CT in predicting prognosis. PMID- 17721331 TI - Small chronic pneumothoraces and pulmonary parenchymal abnormalities after bone marrow transplantation. AB - The features of 4 allogeneic bone marrow transplant patients with an unusual late onset complication of pulmonary abnormalities with small chronic pneumothoraces are described. Thin-section computed tomography demonstrated upper zone fibrotic changes and diffuse abnormalities suggestive of constrictive obliterative bronchiolitis. An important feature of the pneumothoraces was that they tended to be recurrent and small. We suggest that awareness of this unusual association may be useful in the radiologic evaluation of late-onset pulmonary complications after allogeneic bone marrow transplantation. PMID- 17721332 TI - Computed tomography and the idiopathic form of proliferative fibrosing mediastinitis. AB - Fibrosing mediastinitis is characterized by abnormal proliferation of acellular collagen and fibrous tissue in the mediastinum. Although most cases in the United States are attributed to Histoplasma capsulatum, there is a different and important idiopathic subset, with potentially different treatment and prognosis implications. We reviewed 12 such cases encountered from 1995 to 2004. Computed tomography showed that the masses were large, averaging 5 x 9 cm, with none showing significant calcification. Five had extension into the neck, and all had some vascular or airway involvement. Mimics may include the precalcific form of postinflammatory mediastinal fibrosis, mediastinal granuloma, malignancy (esp. lymphoma), sarcoidosis, and Castleman disease. PMID- 17721334 TI - Traumatic pulmonary pseudocysts: CT findings. AB - Traumatic pulmonary pseudocyst constitutes an uncommon, though well recognized, manifestation of closed chest trauma. It is usually encountered in young patients, whose compliant chest wall permits the transmission of great compressive forces to the lung parenchyma and the laceration of the latter. Traumatic pulmonary pseudocyst is usually detected during the imaging evaluation of multi-injured patients with the use of computed tomography, as it is often not apparent in the initial supine anteroposterior chest radiographs. We present 5 cases of trauma patients, in whom we detected the presence of multiple traumatic pulmonary pseudocysts during the imaging evaluation of blunt chest trauma with the use of computed tomography. PMID- 17721333 TI - Computer-aided detection (CAD) in lung cancer screening at chest MDCT: ROC analysis of CAD versus radiologist performance. AB - To evaluate the performance of a computer-aided detection (CAD) algorithm in the detection of pulmonary nodules on high-resolution multidetector row computed tomography images in a large, homogeneous screening population, and to evaluate the effect of the system output on the performance of radiologists, using receiver operating characteristic analysis. Three radiologists with variable experience (1 to 7 y), independently read the 200 computed tomography scans and assigned each nodule candidate a confidence score (1-2-3: unlikely, probably, and definitely a nodule). CAD was applied to all scans; successively readers reevaluated all findings of the CAD, assigning, in consensus, a confidence score (1 to 3). The reference standard was established by the consensus of 2 experienced radiologists with 30 and 15 years of experience. Results were used to generate an free-response receiver operating characteristic analysis. The reference standard showed 125 nodules. Sensitivity for readers I-II-III was 57%, 68%, and 46%. A double reading resulted in an increase in sensitivity up to 75%. With CAD, sensitivity was increased to 94%, 96%, and 94% for readers I, II, and III. The area under the free-response receiver operating characteristic curve (Az) was 0.72, 0.82, 0.55, and 0.84 for readers I, II, III, and the CAD, when considering all nodules. Differences between readers I-II and CAD were not significant (P=0.9). There was a significant difference between reader III and the CAD. For nodules <6-mm Az was 0.40, 0.47, 0.14, and 0.72 for readers I, II, III, and the CAD. Differences between all readers and the CAD were significant (P<0.05). CAD can aid in daily radiologic routine detecting a substantial number of nodules unseen by radiologists. This is true for both board-certified radiologists and for less experienced readers especially in the detection of small nodules. PMID- 17721335 TI - Anterior mediastinal desmoid tumor with CT and MR imaging. AB - Desmoid tumors, or aggressive fibromatoses, are rare, histologically benign tumors with biologic behavior that is intermediate between benign fibrous proliferations and low-grade fibrosarcoma. These tumors can cause significant morbidity and mortality by their propensity for local invasion and recurrence following surgical excision. A case of an anterior mediastinal desmoid tumor in a 67-year-old woman is reported with computed tomography and magnetic resonance imaging findings. PMID- 17721336 TI - Ectopic pancreas in mediastinum: report of 2 cases and review of the literature. AB - Ectopic pancreas in mediastinum is uncommon. In this paper 2 cases of patients who had large cysts or cystic-solid masses containing pancreatic tissue in mediastinum were reported. Although the clinical presentations of these 2 patients were nonspecific, some specific characteristics in the imaging findings were discovered, which will be helpful for the diagnosis. However, the final diagnosis depends on pathologic examination. PMID- 17721337 TI - A case of broncholithiasis and esophagobronchial fistula. AB - Broncholithiasis is the presence of intrabronchial calcification or ossification. We report a case of broncholiths resulting from extrusion of calcified mediastinal lymph node into a bronchus associated with esophagobronchial fistula that became more symptomatic after bronchoscopic removal of the broncholiths. PMID- 17721338 TI - An unusual radiographic manifestation of bronchiolitis obliterans organizing pneumonia. AB - The typical radiographic manifestation of bronchiolitis obliterans organizing pneumonia (BOOP) is bilateral patchy airspace opacities. We present a case of a 52-year-old man with unusual radiographic manifestation of BOOP-diffuse nodularity. We present the x-ray and computed tomography figures with pathologic findings of this case to stress the notion that BOOP should not be omitted by the differential-diagnosis of patients presenting with diffuse nodular pattern on chest imaging. PMID- 17721339 TI - Multidetector computed tomography detection of bronchial diverticula. AB - Bronchial diverticula are associated with chronic obstructive pulmonary disease. With newer scanners, small structures such as these air-filled diverticula will be visible and could be mistaken for pneumomediastinum. We present a case in which retrospectively reconstructed thin-section computed tomography clearly depicted the presence of multiple bronchial diverticula enabling the diagnosis to be made with certainty. PMID- 17721340 TI - Intravascular sarcoidosis presenting as pulmonary vein occlusion: CT and pathologic findings. AB - It is well known that destruction of the distal capillary bed from extensive fibrosis and honeycombing in the setting of sarcoidosis may lead to pulmonary hypertension. However, we report an unusual manifestation of sarcoidosis where pulmonary hypertension resulted from granulomatous involvement of the pulmonary veins and venules. This presented as venous occlusion and intraluminal filling defects that simulated thrombus on chest computed tomography. To our knowledge, this is the first reported imaging case of such a presentation. PMID- 17721341 TI - Babesiosis: CT and hematologic findings. AB - Babesiosis is a tick-borne illness caused by the protozoan Babesia microti. Most patients are asymptomatic but the infection may produce a spectrum of symptoms in immunocomprimised patients, especially asplenic patients. These range from mild fever, sweats, fatigue, and myalgias to severe multiorgan failure, including acute respiratory distress syndrome and death. Radiographic appearances include bilateral patchy air space and interstitial opacities. We report the radiographic, high-resolution computed tomography (HRCT), and hematologic appearances in a 63-year-old man presenting with acute babesisois. HRCT images revealed smooth septal thickening and intralobular lines superimposed on ground glass opacities in both upper lobes. Follow-up HRCT after 2 weeks of therapy demonstrated resolution of the pulmonary parenchymal abnormalities. PMID- 17721343 TI - CT findings in acute myocarditis: 2 cases. AB - Myocarditis is a serious and life-threatening illness, which can pose a significant diagnostic dilemma at presentation. We report 2 patients with clinical myocarditis who had distinctive findings at coronary computed tomography. Both patients demonstrated delayed myocardial enhancement with iodinated contrast. The morphologic features of the enhancement were similar to the myocardial enhancement with gadolinium contrast on magnetic resonance imaging recently described in patients with myocarditis, and different from the enhancement patterns seen in patients with myocardial infarction. These findings are not previously reported in the literature. As computed tomography is more widely available for use in the acute setting than magnetic resonance imaging, these findings may have significant clinical utility and warrant further investigation. PMID- 17721342 TI - Identification of a coronary-to-bronchial-artery communication with MDCT shows the diagnostic potential of this new technology: case report and review. AB - Development and refinement of multidetector computed tomography (MDCT) has brought the potential to replace conventional coronary angiography with a noninvasive technique that has comparable spatial and temporal resolution with a single breath-hold. Although clinical use of MDCT has largely been confined to evaluation of atherosclerotic coronary artery burden and coronary artery anomalies, it can be applied to diagnosis of other problems concerning the thoracic vasculature. We present the case of a middle-aged man who presented with recent-onset exertional angina: 64-detector CT was used as an alternative to cardiac catheterization and identified the underlying anatomic anomaly, a rare coronary-to-bronchial-artery communication. Clinicians should be aware that the newest generation of MDCT equipment may allow many patients to forego diagnostic cardiac catheterization without compromise in quality of care. PMID- 17721344 TI - Cardiac herniation after right pneumonectomy: case report and review of the literature. AB - Cardiac herniation is a rare condition, which is often lethal in unrecognized cases. It is most commonly seen after pneumonectomy with associated pericardiotomy or pericardiectomy but has been reported in patients with iatrogenic, traumatic, and congenital pericardial defects. It is important that the radiologist be aware of this entity, as delay in diagnosis may be fatal. In this paper, we will discuss a case of cardiac herniation after right pneumonectomy and review the radiologic literature. PMID- 17721345 TI - Atrioesophageal fistula after catheter pulmonary venous ablation for atrial fibrillation: imaging features. AB - Atrioesophageal fistula is a rare but highly morbid complication of catheter mediated pulmonary vein ablation for the treatment of atrial fibrillation. Among patients who do not exsanguinate from upper gastrointestinal tract bleeding, presentation includes sepsis and embolic cerebrovascular disease. We present a case of atrioesophageal fistula after pulmonary venous ablation as a treatment for atrial fibrillation, focusing on the imaging features of this diagnosis. PMID- 17721346 TI - Smoking-related emphysema and interstitial lung diseases. AB - Smoking-related illnesses contribute to a large number of deaths in the industrialized world and their treatment comprises a substantial percentage of total healthcare dollars. The most common and most well-known smoking-related illnesses include chronic obstructive pulmonary disease, bronchogenic carcinoma, and ischemic heart disease. However, the role of cigarette smoking in the pathogenesis of other lung diseases is becoming increasingly apparent. Knowledge of both the histologic and radiographic manifestations of smoking-related lung disease is important to the radiologist as imaging findings can be nonspecific. Finally, correlation of imaging and clinical information may obviate the need for open lung biopsy. PMID- 17721347 TI - Viral pneumonia after hematopoietic stem cell transplantation: high-resolution CT findings. AB - Hematopoietic stem cell transplantation (HSCT) is the treatment of choice for many hematologic malignancies and nonmalignant disorders of bone marrow function. Pulmonary infections from bacterial, fungal, and viral organisms are a major cause of morbidity and mortality in patients after HSCT. The radiographic and high-resolution computed tomography (HRCT) findings of the different lower respiratory tract viral infections are quite similar. Findings of viral pneumonia on HRCT include small poorly defined centrilobular nodules and patchy, often bilateral, areas of peribronchial ground-glass opacity and consolidation. Air trapping may be present because of associated bronchiolitis. Interlobular septal thickening, bronchial wall thickening, and tree-in-bud opacities may also be present. Advanced viral pneumonia with diffuse alveolar damage is characterized by patchy or confluent consolidation and ground-glass opacities. Although nonspecific, in the correct clinical setting, these HRCT findings can help suggest the diagnosis of viral pneumonia in recipients of HSCT. PMID- 17721348 TI - MDCT of tracheobronchial narrowing in pediatric patients. AB - Chest radiographs have been useful for the incidental detection and initial imaging evaluation of clinically suspected central airway narrowing in pediatric patients. However, cross-sectional imaging, such as computed tomography (CT), is frequently required for confirmation of diagnosis, further characterization, and preoperative evaluation of surgical lesions. Recent rapid technologic advancement in CT has allowed CT to assume a pivotal role in the noninvasive evaluation of tracheobronchial narrowing in children, in particular with multidetector computed tomography with postprocessing techniques, including multiplanar reformations and 3-dimensional reconstructions. In this article, the authors review the multidetector computed tomography technique for evaluation of central airway narrowing in children, with emphasis on the use of multiplanar reformations and 3 dimensional reconstructions in the imaging evaluation of the spectrum of intrinsic and extrinsic causes of central airway narrowing in children. PMID- 17721350 TI - New physical activity guidelines bring clarification. PMID- 17721351 TI - Drug-induced vitamin B12 deficiency. PMID- 17721352 TI - Reflex sympathetic dystrophy: a case of total body pain. PMID- 17721353 TI - Guide to care for patients. Cold vs. flu. PMID- 17721354 TI - Crush injuries: pathophysiology and current treatment. PMID- 17721355 TI - Herpes zoster: prevention, diagnosis, and treatment. PMID- 17721357 TI - Assessment and management of urinary incontinence in the elderly male. PMID- 17721359 TI - Pain management: patients with a substance use disorder. PMID- 17721360 TI - The role of the nurse practitioner in cases of child sexual abuse. PMID- 17721362 TI - Using the Glasgow Benefit Plot as a prognostic instrument and for preoperative counseling in patients with otosclerosis. AB - OBJECTIVE: The Glasgow Benefit Plot (GBP) is a graph showing the pure-tone thresholds preoperatively and postoperatively, and is meant to visualize the possible outcome of binaural hearing for individual patients. We used our database comprising a large number of patient data to test the usefulness of the GBP. STUDY DESIGN: Evaluation based on retrospective clinical data. SETTING: Tertiary referral center, University clinic. MAIN OUTCOME MEASURES: Audiometric assessment included bilateral preoperative and postoperative evaluation using conventional audiometry. Three preoperative groups (unilateral, asymmetric, and symmetric hearing impairment) were split into 6 postoperative categories in the GBP diagram. RESULTS: Considering the 509 operations, including 34 bilateral operations, the total outcome was distributed as follows: 34% resulted in bilateral normal hearing, 24% unilateral normal hearing (in operated ear), 14% still unilateral hearing impairment (in operated ear), 13% symmetric hearing impairment, 10% asymmetric hearing impairment (operated ear best), 5% still asymmetric hearing impairment (nonoperated ear best). The distribution of outcomes depended in part on the bone conduction level in the operated ear and in part on the hearing status in the contralateral ear. CONCLUSION: The GBP is a useful instrument that provides a means for judging the binaural hearing status. However, the outcome of stapes surgery for individual persons and for a group depends critically on the preoperative audiometric criteria for patients who are chosen for surgery. In cases of depressed bone conductions, the method does not indicate the upper limit for possible hearing improvement. A number of patients with combined hearing impairments were included in the present study population. In preoperative counseling, the GBP must be complemented with information with regard to the limitation of possible hearing improvement owing to the individual bone conduction level. PMID- 17721363 TI - Otoacoustic emissions in early noise-induced hearing loss. AB - OBJECTIVE: To follow changes in transient evoked and distortion product otoacoustic emissions (TEOAEs, DPOAEs) as they relate to pure-tone audiometry (PTaud) thresholds during the first 2 years of occupational noise exposure. DESIGN: Prospective controlled. METHODS: Pure-tone audiometry thresholds, TEOAE and DPOAE amplitudes, and contralateral medial olivocochlear reflex strength were repeatedly evaluated during 2 years and compared between and within a cohort of 135 ship engine room recruits and a control group of 100 subjects with no noise exposure. RESULTS: Pure-tone audiometry thresholds for 2,000, 3,000 and 4,000 Hz in both ears were significantly elevated in the study group after 2 years of noise exposure. Significantly lower TEOAE amplitudes were found at 2,000 Hz in the right ear and 2,000 and 4,000 Hz in the left ear. Longitudinal intrasubject analysis of the study group revealed significant reductions of TEOAE amplitudes at 2,000 to 4,000 Hz in both ears and reduced DPOAE amplitudes for 5,957 Hz in the right ear and 3,809, 4,736, and 5,957 Hz in the left ear in the second follow up evaluation. Baseline medial olivocochlear reflex strength showed no correlation to PTaud thresholds after 2 years of noise exposure. Poor to moderate negative linear correlations (r = -0.07 to -0.37) were found between the DPOAE averaged amplitudes at 2,979 to 5,957 Hz and PTaud threshold means at 3,000 to 6,000 Hz. Abnormal TEOAE parameters after the first year of noise exposure had high sensitivity (86-88%) and low specificity (33-35%) for the prediction of noise-induced hearing loss (NIHL) after 2 years. CONCLUSION: The DP-gram is not significantly correlated with PTaud and cannot be used as an objective measure of pure-tone thresholds in early NIHL. Medial olivocochlear reflex strength before the beginning of chronic exposure to occupational noise has no relation to individual vulnerability to NIHL. Although TEOAEs changes after 1 year showed high sensitivity in predicting NIHL after 2 years of exposure, they cannot be recommended as an efficient screening tool due to high false-positive rates. PMID- 17721364 TI - Positional vertigo and cochlear implantation. AB - OBJECTIVE: To identify patients developing positional vertigo after cochlear implantation. STUDY DESIGN: Prospective study on a cohort of patients undergoing cochlear implantation. SETTING: Academic tertiary referral center. PATIENTS: The study included 70 consecutive patients who underwent vestibular evaluation before and after cochlear implantation. INTERVENTION: Medical record review. MAIN OUTCOME MEASURE: Recorded vestibular symptoms after cochlear implantation. Patients with positional vertigo were considered case subjects, whereas those without vestibular symptoms were considered case controls. RESULTS: Benign paroxysmal positional vertigo (BPPV) occurred in 8 patients (on the cochlear implant [CI] side in 7 patients, and in the other ear in 1). One patient had BPPV of the lateral semicircular canal on the implanted side, and 7 patients had BPPV of the posterior semicircular canal (on the same CI side in 6 patients, and on the opposite side in 1), which were detected and presented during the last examination. In 5 patients, the onset of symptoms varied from 7 to 130 days after implant activation; in 2 patients, the onset occurred before activation. CONCLUSION: Three different mechanisms are proposed for the occurrence of BPPV in patients with CI. The first focuses on the fall of bone dust particles into the cochlea during cochleostomy. In the second, the vibration caused by drilling the cochlea would be sufficient to dislodge otoconia into the labyrinth. The third hypothesis suggests dislodging of an otolith because of the electric stimulation. In our patients, conservative approaches have been used with a minimal invasive cochleostomy and without perilymph suction. Thus, the vibratory trauma affecting the cochlea during cochleostomy seems to play a fundamental role in the development of paroxysmal vertigo in patients with implant. PMID- 17721366 TI - Bone-anchored hearing aid in patients with moderate mental retardation: impact and benefit assessment. AB - OBJECTIVE: To assess the impact and the subjective benefit of Bone-anchored Hearing Aid (BAHA) implementation in patients with hearing impairment combined with moderate mental retardation. STUDY DESIGN: Case control study using two validated patient-oriented instruments. SETTING: Tertiary referral center. PATIENTS: Twenty-two patients with moderate mental retardation and conductive or mixed hearing loss. INTERVENTION: Rehabilitative. MAIN OUTCOME MEASURES: Subjective benefit, listening and learning capabilities. RESULTS: BAHA implementation in patients with moderate mental retardation, by using the Glasgow Children's Benefit Inventory and the Listening Inventory for Education, showed a subjective benefit, which was comparable with that of the control group and was consistent with the results of earlier studies. CONCLUSION: The use of BAHA proved beneficial in most patients with hearing impairment and moderate mental retardation. Extending the indications for BAHA application to this special patient group shows to be a very valuable option. PMID- 17721365 TI - Necrotizing external otitis: a report of 46 cases. AB - OBJECTIVES: To define germs involved, clinical presentation, treatment regimen, and prognostic factors in necrotizing external otitis. PATIENTS AND METHODS: Retrospective study reviewing a series of 46 patients treated during 10 years in a tertiary care center. Diagnosis was confirmed by using otomicroscopy, computed tomographic and/or magnetic resonance imaging scan and bone scintigraphy (Te 99 and Ga 26 bone scan). Patients were provided ceftazidime and ciprofloxacin intravenously and monitored using a Ga-67 bone scan. The following were assessed: presenting symptoms, general context, bacteriological analysis, imaging protocol sensitivity, complications, delay to healing, and cure rate. RESULTS: Sex ratio was 2.29 (mean age, 73.6 yr). The most common presenting symptoms were otalgia and otorrhea in 97.8 and 91.3%, respectively. Facial paralysis was present in 19.6% of cases. Thirty patients had diabetes mellitus (65.2%), and 8 were immunocompromised (17.4%). Pseudomonas aeruginosa was isolated in 69.2% of cases and was resistant to ciprofloxacin in 18.5%, but was susceptible to ceftazidime in all cases. Four patients died during the treatment (4.4%), but only 2 of disease. The mean delay to healing was 14 weeks (SD, 9.7). Healing rate was 95.6%. No relapse was observed after a mean follow-up of 78.4 weeks (SD, 36.5 wks). Two factors significantly influenced the prognosis: facial paralysis and existence of systemic factors for immune deficiency (p = 0.023 and 0.038, respectively). CONCLUSION: The association of ciprofloxacin and ceftazidime was efficient in countering the increasing resistance of P. aeruginosa to quinolones. We propose a prognostic classification of necrotizing external otitis based on the presence of facial paralysis and/or systemic factors. PMID- 17721368 TI - Insufficient cranial thickness in bone-anchored hearing aid placement. PMID- 17721367 TI - Monitoring of caloric response and outcome in patients with benign paroxysmal positional vertigo. AB - OBJECTIVE: To analyze the time course of caloric response in patients with Benign Paroxysmal Positional Vertigo (BPPV). PATIENTS: Seventy-four individuals with diagnosis of BPPV during Dix-Hallpike (DH) test. STUDY DESIGN: A prospective, longitudinal study. SETTING: A tertiary referral center. INTERVENTION: Patients were treated by particle repositioning maneuvers according to the affected canal, and the effectiveness was evaluated at 180 and 360 days. Bithermal caloric response was obtained by using 44 and 30 degrees C water irrigations at diagnosis, 6 months, and 1 year after. MAIN OUTCOME MEASURE: Canal paresis (CP) and response to DH after treatment. RESULTS: The effectiveness of the treatment for BPPV (absence of vertigo and positional nystagmus during DH) was 65.2% (45 of 69) after 1 year of follow-up. Twenty-five percent of (16 of 64) individuals with BPPV presented CP at diagnosis, 27% (12 of 44) at 6 months, and 16% (9 of 56) 1 year after. One year after, seven individuals with CP showed a normal caloric response, another seven demonstrated persistent CP, and one case developed a bilateral CP. The effectiveness of particle repositioning maneuvers was not significantly different between subjects with or without CP after 1 year of follow-up (odds ratio, 1.31 [95% confidence intervals, 0.35-4.89], p = 0.88). CONCLUSION: Canal paresis is not associated with a lower outcome to repositioning. PMID- 17721369 TI - Surveillance for invasive pneumococcal disease during 2000-2005 in a population of children who received 7-valent pneumococcal conjugate vaccine. AB - OBJECTIVES: To assess the incidence of invasive pneumococcal disease (IPD) in all children younger than 5 years of age in the Northern California Kaiser Permanente (NCKP) health care system during a 5-year surveillance period (2000-2005) after the introduction in April 2000 of routine use of 7-valent pneumococcal conjugate vaccine (PCV7). METHODS: This was a laboratory-based surveillance study of all children younger than 5 years of age in the NCKP health care system from April 2000 to March 2005. The comparison group was all children younger than 5 years of age in the NCKP health care system from April 1996 to March 2000. Data obtained from clinical databases included microbiologic identification and susceptibility testing; serotyping of isolates; immunization records; and IPD diagnoses for inpatients and outpatients. IPD was defined as a positive culture of Streptococcus pneumoniae from a normally sterile body site. RESULTS: For all serotypes, the mean annual incidence of IPD during the postlicensure surveillance period was 15.3 cases/100,000 person-years (10(5) p-y) compared with 62.5 cases/10(5) p-y in the prelicensure years of 1996-2000. The average incidence of IPD caused by vaccine serotypes was reduced from 50.1 cases/10(5) p-y during the prelicensure years to 4.9 cases/10(5) p-y during the postlicensure period. The average incidences of IPD caused by cross-reactive and by nonvaccine serotypes were 5.8 and 5.3 cases/10(5) p-y, respectively, during the prelicensure years and 2.5 and 6.2 cases/10(5) p-y, respectively, during the postlicensure period. Of the 131 IPD cases observed during the postlicensure surveillance period, bacteremia (50.4%) and pneumonia (31.3%) were the most common diagnoses. During the 5-year postlicensure surveillance period, only 3 subjects who were identified to be fully vaccinated for age with PCV7 (3 doses by 7 months of age or 4 doses by 18 months of age) developed vaccine-serotype IPD. CONCLUSION: The incidence of IPD has significantly decreased in a large population of children after the introduction of PCV7. Vaccine-type IPD was rare in patients who received full 4 dose immunization with PCV7. There is no clear evidence of a significant increase in nonvaccine-serotype IPD. Introduction of a 4-dose infant schedule of PCV7 into this population has resulted in a marked and sustained reduction of IPD in children. PMID- 17721370 TI - Temporal relationships for cold-like illnesses and otitis media in sibling pairs. AB - BACKGROUND: New otitis media (OM) episodes are most frequently a complication of cold-like illnesses (CLIs) which are often virus infections that can be exchanged within the family unit. Interference with intrafamily CLI transmission may present a strategy for OM prophylaxis in high risk children. This study estimated factors relevant to strategy efficiency. METHODS: Two siblings (ages, 1.0-4.3 and 1.7-6.1 years) from 69 families were followed for 193 days beginning in October using daily parental diaries focused on CLI signs and weekly pneumatic otoscopy to diagnose OM presence/absence. An algorithm converted the signs to presence/absence of a cold-day; cold-days were grouped into CLI episodes, and episodes were examined for intersib transmission and OM complications. RESULTS: We identified 267 CLIs in the younger siblings and 221 in the older siblings. Twenty-seven percent of the CLI episodes in one sibling occurred after CLI onset in the other with a median interval of 3 days. Sixty-two percent of newly diagnosed OM episodes occurred during a CLI and 27% of CLIs were complicated by OM. Analysis of factors that could affect CLI incidence documented significant contributions of gender, age, daily environment and the CLI burden in the sibling with expected directionalities. CONCLUSION: The results document intrafamily transmission of CLIs that is often associated with the development of OM as a complication. These observations and the measured interval between primary and secondary CLI onsets support the possibility of preventing OM by strategies that target intrafamily CLI transmission. PMID- 17721371 TI - Large measles outbreak at a German public school, 2006. AB - BACKGROUND: In 2006, a large measles outbreak (n = 614) occurred in Duisburg city, Germany, with 54% of cases aged >9 years. An investigation was launched to determine reasons for the resurgence of measles, assess vaccination coverage and vaccine effectiveness (VE). METHODS: A retrospective cohort-study was undertaken at a Duisburg public school affected early in the outbreak. We distributed questionnaires to all 1250 students aged 10-21 years and abstracted vaccination records. Cases were identified according to a standard clinical case definition. RESULTS: Questionnaires were returned by 1098 (88%) students. Vaccination records were abstracted from 859 students, of whom 820 (95.4%) had received at least one, 605 (70.4%) 2, and 39 (4.5%) no dose(s) of measles-containing vaccine (MCV). Coverage with 2 doses was higher in younger students. We identified 53 cases (attack rate = 5%). Measles-virus sequencing revealed genotype D6. After excluding students vaccinated in 2006 and those with a history of measles, the attack rate was 53% in unvaccinated students, 1.0% in students with one, and 0.4% in those with 2 MCV-doses. VE was 98.1% (95% CI: 92-100%) in students with one and 99.4% (95% CI: 97-100%) with 2 MCV-doses. Based on observed attack rates in vaccinated and unvaccinated students with vaccination records and in students without vaccination records, one-dose-coverage among all participating students was estimated at 91%. CONCLUSIONS: VE was high. Vaccination coverage was, however, insufficient to prevent the outbreak. Immunization gaps were found especially in older students. To prevent further outbreaks and to achieve the goal of measles elimination in Germany, vaccination coverage must be increased. PMID- 17721372 TI - Concomitant administration of a virosome-adjuvanted hepatitis a vaccine with routine childhood vaccines at age twelve to fifteen months: a randomized controlled trial. AB - BACKGROUND: The objectives of this trial were to test for noninferiority of a virosomal hepatitis A virus (HAV) vaccine (Epaxal) coadministered with routine childhood vaccines compared with Epaxal given alone and to an alum-adjuvanted HAV vaccine (Havrix Junior) coadministered with routine childhood vaccines. METHODS: Healthy children 12- to 15-month-old were randomized to receive either a pediatric dose (0.25 mL) of Epaxal coadministered with DTPaHibIPV, oral polio vaccine, and measles-mumps-rubella vaccine (n = 109; group A), or Epaxal given alone (n = 105; group B), or Havrix Junior coadministered with DTPaHibIPV, oral polio vaccine, and measles-mumps-rubella vaccine (n = 108; group C). A booster dose was given 6 months later. Anti-HAV antibodies were tested before and 1 month after each vaccination. Safety was assessed for 1 month after each vaccination. Solicited adverse events were assessed for 4 days after each vaccination. RESULTS: : HAV seroprotection rates (> or =20 mIU/mL) at 1 and 6 months after first dose were: A: 94.2% and 87.5%, B: 92.6% and 80.0%, C: 78.2% and 71.3%, respectively (A versus C: P < 0.001 and P = 0.017 at month 1 and 6, respectively). The respective geometric mean concentrations were: A: 51 and 64 mIU/mL, B: 49 and 59 mIU/mL, C: 33 and 37 mIU/mL (A versus C: P < 0.001 at both time points). All groups achieved 100% seroprotection after the booster dose. The geometric mean concentrations after the booster dose were 1758, 1662, and 1414, for groups A, B and C, respectively (A versus C: P = 0.15). No clinically significant reduction in immune response to all concomitant vaccine antigens was seen. All vaccines were well tolerated. CONCLUSIONS: : Coadministration of pediatric Epaxal with routine childhood vaccines showed immunogenicity and safety equal to Epaxal alone as well as to Havrix Junior. After first dose, Epaxal was significantly more immunogenic than Havrix Junior. PMID- 17721373 TI - Admission clinical and laboratory factors associated with death in children with cancer during a febrile neutropenic episode. AB - BACKGROUND: Early identification of children with cancer at risk for death during a febrile neutropenic (FN) episode may increase their possibility for survival. Our aim was to identify at the time of admission, clinical and laboratory variables differing significantly among children who survived or died during a FN episode. METHODS: In a prospective, multicenter study, children admitted with a high-risk FN episode were uniformly evaluated at enrollment and managed according to a national consensus protocol. Medical charts of children who died were evaluated to determine whether the death could be associated with an infection. Admission clinical and laboratory variables significantly associated with death were identified. RESULTS: A total of 393 (70%) of 561 FN episodes evaluated from June 2004 to December 2005 were classified as high risk for invasive bacterial infection, of which 14 (3.6%) resulted in an infectious-related death. Deaths occurred from 2 to 27 days after admission, and most dying children were admitted with relapse of acute lymphocytic leukemia (36%), hypotension (71%), and a diagnosis of sepsis (79%), compared with surviving children (16%, 20%, and 5% respectively, P < 0.001). Children who died were admitted with lower absolute neutrophil count (P < 0.001) and absolute monocytes count levels (P = 0.008), higher blood urinary nitrogen (P = 0.03) and C-reactive protein values (P < 0.001), and had more positive cultures (79% versus 32%, P = 0.008). CONCLUSIONS: We identified early clinical and laboratory findings significantly associated with death occurring at a later stage. Routine evaluation of these variables may prove to be useful in the early identification of children with a high-risk FN episode at risk for death. PMID- 17721374 TI - Safety and efficacy of enfuvirtide for 48 weeks as part of an optimized antiretroviral regimen in pediatric human immunodeficiency virus 1-infected patients. AB - BACKGROUND: Enfuvirtide is the only entry inhibitor approved for the treatment of human immunodeficiency virus (HIV)-1 infection. It is approved for use in adults and dosage recommendations exist for children aged 6 years or older. METHODS: T20 310 was a multicenter, open-label, nonrandomized, noncomparative study of the safety and efficacy of 2.0 mg/kg (maximum 90 mg) twice-daily subcutaneous enfuvirtide for 48 weeks in 52 treatment-experienced, HIV-1-infected pediatric patients (3-16 years) receiving optimized background therapy. RESULTS: Enfuvirtide was generally well tolerated, and no new patterns of adverse events compared with adults were observed. Mild-to-moderate injection-site reactions were the most common adverse event. Of those participants on treatment for 48 weeks, the median change from baseline in HIV-1 RNA was -1.17 log10 copies/mL (n = 32), and there was a median CD4 change of +106 (n = 25) cells/mm3 and +4.7 CD4%. Seventeen (32.7%) patients achieved a viral load decrease of > or =1 log10 copies/mL and 11 (21.2%) achieved HIV-1 RNA <400 copies/mL. Virologic and immunologic treatment responses were substantially better for children (<11 years) than adolescents. Steady-state mean enfuvirtide C(trough) levels were stable during 24 weeks with no differences between children and adolescents. CONCLUSIONS: Enfuvirtide is an effective treatment for HIV-1 infection in children and adolescents receiving optimized background therapy and has a favorable safety profile. Efficacy in adolescents was inferior; probably related to unique adherence challenges. The long-term safety and efficacy of enfuvirtide in pediatric patients is comparable to that observed in adults. PMID- 17721375 TI - Impact of a pertussis booster vaccination program in adolescents and adults on the epidemiology of pertussis in Austria. AB - BACKGROUND: A resurgence of pertussis has been observed in several countries; however, inconsistent data are available for Europe. In Austria, routine pertussis vaccination for babies is administered at 3, 4, and 5 months, and in the second year of life. Since 2002, regular boosters for all persons >6 years of age (including adults) are recommended. This study was undertaken to analyze epidemiologic trends of laboratory-reported pertussis to evaluate current vaccination strategy in Austria. METHODS: Epidemiologic surveillance of laboratory-reported pertussis was conducted from January 1, 2000, to December 31, 2005. Infection was confirmed by positive serology, by positive culture of Bordetella pertussis, or by detection of sequences of the pertussis toxin gene by real-time polymerase chain reaction (RT-PCR). Data were assessed by age, hospitalization rate, seasonality, and incidence rate. RESULTS: During the observation period 4395 reported cases of pertussis were eligible for analysis. The mean annual incidence increased from 6.4 per 100,000 population in 2000 to 11.1 cases per 100,000 population in 2005. Incidence rates were highest among children less than 1 year of age. Decreasing rates were observed for children and adolescents <16 years of age, whereas increasing rates were detected for persons 16 years of age and older. The mean age of reported pertussis cases increased from 30 years (+/-25.9 SD) in 2000 to approximately 44 years (+/-23.7 SD) in 2005. Hospitalization rates were highest in infants <6 months (86%) and lowest in those 10 to <50 years of age (17%), followed by an increase to 80% in persons 85 years of age and older. In general, no seasonal occurrence of disease was apparent. CONCLUSIONS: Pertussis incidence remains high among adults implying that coverage rates regarding booster vaccinations for adolescents and adults still are too low. Reinforced application of the current booster strategy is needed. PMID- 17721376 TI - Mother-to-child transmission of Chikungunya virus infection. AB - BACKGROUND: In 2005-2006 Reunion Island experienced a massive outbreak of chikungunya, a mosquito-borne alphavirus infection. During this epidemic, early neonatal cases were observed with a highly probable mother-to-child transmission. METHODS: A retrospective descriptive study was conducted in 5 neonatal medicine departments. Chikungunya virus infection was confirmed by reverse transcription polymerase chain reaction or specific serology in mothers and their newborns. Mothers were screened if they presented signs at delivery or if their neonates became ill on the first days of life. RESULTS: Thirty-eight neonates were enrolled. All mothers, except 2 asymptomatic mothers, presented signs during the perinatal period (range, day(D) -4 to D+1). All neonates were symptomatic and presented symptoms on D3 to D7 (mean, D4). The mean interval between onset of maternal illness and onset of neonatal illness was 5 days (range, 3-9). The most frequent clinical signs in neonates were fever (79%), pain (100%), rash (82%), and peripheral edema (58%). Thrombocytopenia (76%), lymphopenia (47%), decreased prothrombin value (65%), and elevation of aspartate aminotransferase (77%) were detected. Complications included seizures (6), hemorrhagic syndrome (6), and hemodynamic disorders (10). Reverse transcription-polymerase chain reaction in cerebrospinal fluid was positive in 22 of 24 cases, and abnormal findings on brain magnetic resonance imaging (14 of 25) with white matter lesions or intraparenchymal hemorrhages or both were found. Echocardiography (16) showed myocardial hypertrophy (5), ventricular dysfunction (2), pericarditis (2), and coronary artery dilatation (6). One neonate died of necrotizing enterocolitis. CONCLUSIONS: The chikungunya epidemic that occurred on La Reunion Island revealed for the first time the possibility of mother-to-child transmission in the perinatal period with a high rate of morbidity. PMID- 17721378 TI - Kawasaki disease in Korea, 2003-2005. AB - PURPOSE: The aim of this study was to investigate the incidence rate and epidemiologic patterns of Kawasaki disease in Korea for the 3-year-period, 2003 2005. METHODS: The questionnaire for an epidemiologic survey on Kawasaki disease was distributed to all 102 Korean hospitals that conduct pediatric residency programs, and obtained data were analyzed upon receipt. RESULTS: The 9662 patients of Kawasaki disease from 85 hospitals that responded (response rate, 83.3%) consisted of 5877 males and 3785 females (male:female ratio, 1.55:1). The incidence rate per 100,000 children <5-year-old was 104.2 in 2003, 106.4 in 2004, and 104.6 in 2005 (average rate, 105.0). Their mean age of onset was 33.3 months, and the proportions of sibling cases and recurrent cases were 0.29% and 2.0%, respectively. Coronary arterial abnormalities were detected at follow-up by echocardiogram in 18.8% of all such cases including dilatations of 18.0% and aneurysms of 2.5%. CONCLUSION: The average annual rate of incidence, 105.0/100,000 in children <5-year-old is the second highest reported rate in the world. PMID- 17721379 TI - Antibody persistence and booster vaccination during the second and fifth years of life in a cohort of children who were born prematurely. AB - BACKGROUND: These studies assessed the immunogenicity and reactogenicity of booster vaccination with diphtheria-tetanus-acellular pertussis-hepatitis B inactivated poliovirus-adsorbed conjugated Haemophilus influenzae type b (DTaP HBV-IPV/Hib) at 18-20 months, and with DTaP during the fifth year of life in children who had been born prematurely (<37 weeks gestation). METHODS: Open label, parallel group studies in which preterm and full-term subjects primed with DTaP-HBV-IPV/Hib received booster vaccination with DTaP-HBV-IPV/Hib (Infanrix hexa) at 18-20 months and DTaP (Infanrix) at 4 years of age. Immunogenicity was assessed before and 1 month after DTaP-HBV-IPV/Hib dose and 1 month after DTaP administration. Local and general symptoms were recorded for 4 days, unsolicited symptoms for 31 days after each dose. RESULTS: Before the second year booster, Hib, hepatitis-B, and polio type 3 seroprotection rates were higher in the full term group (antipolyribosyl ribitol phosphate > or =0.15 microg/mL observed in 76.2%/83.6% preterm/full term respectively, anti-HBs > or =10 mIU/mL in 75.0%/80.6% respectively). One month after the DTaP-HBV-IPV/Hib booster, > or =98% in both groups were seroprotected/seropositive for all vaccine antigens, except hepatitis-B in preterms (seroprotection rate 91.6%). By the fifth year hepatitis-B seroprotection rates were 85.3%/70.5% (preterm/full term) in subjects who had previously responded to hepatitis-B vaccination, and seroprotection rates for polio and polyribosyl ribitol phosphate were >95%. No differences between groups were observed after the DTaP booster. Both booster doses were generally well tolerated with minimal differences observed between groups. Local symptoms occurred more frequently after the fifth vaccination at 4 years of age. CONCLUSIONS: Despite trends for lower immune responses to some vaccine antigens in preterm subjects, these findings support undelayed primary and booster vaccination in infants and children born before term. Booster vaccinations with DTaP-HBV-IPV/Hib and DTaP were well tolerated in this susceptible group. PMID- 17721377 TI - Observational trial of antibiotic-coated central venous catheters in critically ill pediatric patients. AB - BACKGROUND: Catheter-associated bloodstream infections (CABSI) are among the most common and serious adverse events experienced by critically ill children. Randomized trials have demonstrated that the use of central venous catheters (CVC) coated with antiseptic solutions reduces rates of CABSI in adult patients; however, their efficacy in children has not been evaluated. OBJECTIVE: To compare the incidence of CABSI, rate of complications, and microbiology of infection in critically ill children treated with antibiotic-coated or noncoated CVC (NC-CVC). METHODS: A prospective observational trial was conducted in the pediatric intensive care unit (PICU) during a 13-month period. A minocycline-rifampin coated CVC (MR-CVC) or NC-CVC was placed by PICU physicians who nonpreferentially selected CVC type. RESULTS: We studied the outcomes associated with the first CVC placed in 225 patients, including 69 MR-CVC and 156 NC-CVC. Patients who received MR-CVC, as compared with NC-CVC, were similar in gender, age, and severity of illness at time of PICU admission. The incidence density of CABSI did not vary by catheter type [MR-CVC: 7.53 per 1000 catheter-days (95% confidence interval 2.05 19.17); NC-CVC: 8.64 CABSI per 1000 catheter-days (95% confidence interval 3.74 16.96)]. However, the median time to infection in children with MR-CVC was 3-fold longer than in children with NC-CVC [18 versus 5 days (P = 0.053)]. No difference was seen in the incidence of complications, including thrombosis and catheter site reaction, between MR- and NC-CVC. No significant difference was observed in the types of organisms recovered from patients with MR- and NC-CVC. CONCLUSIONS: The use of MR-CVC significantly delayed the onset of CABSI in PICU patients. Larger, randomized trials are needed to better define potential differences in the incidence of CABSI, rate of complications, and microbiology of infection among pediatric patients treated with antiseptic-coated CVC and NC-CVC. PMID- 17721380 TI - Fetal risk associated with rubella vaccination during pregnancy. AB - BACKGROUND: Costa Rica implemented a nationwide measles-rubella vaccination campaign among men and women (15-39 years old) in May 2001. A protocol was developed to follow-up the vaccinated women who were unknowingly pregnant, to determine the risk of congenital rubella syndrome (CRS) or congenital rubella infection only associated with the administration of the rubella vaccine RA27/3 during pregnancy. METHODS: To classify the prevaccination maternal immune status, a serum sample was taken at the initial evaluation to detect IgM and IgG rubella antibodies (enzyme-linked immunosorbent assay). All pregnancies were followed up and all newborns were evaluated. A cord serum sample of their children was taken at birth. We calculated odds ratio, OR (95% confidence interval, 95% CI) associated with miscarriage, stillbirth, prematurity, low birth weight, and the presence of defects compatible with CRS. RESULTS: The prevaccination immune status was established in 797 women and 1191 mother and child pairs were analyzed. Adjusted OR for miscarriage (OR = 0.60, 95% CI = 0.26-1.39), stillbirth (OR = 1.32, 95% CI = 0.10-16.81), prematurity (OR = 0.25, 95% CI = 0.03-2.39), low birth weight (OR = 0.25, 95% CI = 0.03-2.23) and defects compatible with CRS (OR = 1.09, 95% CI = 0.34-3.54) showed no association between immune and susceptible maternal status. There were no cases of CRS and no children were IgM positive. CONCLUSIONS: No adverse pregnancy outcome such as miscarriages or CRS was documented in women who were vaccinated and unknowingly pregnant. These results support RA27/3 rubella vaccine safety. PMID- 17721381 TI - Prevalence of human papillomavirus in the oral cavity/oropharynx in a large population of children and adolescents. AB - OBJECTIVE: Human papillomavirus (HPV) in the oral cavity or oropharynx is associated with an increased risk of laryngeal papillomatosis, head and neck cancer, and cervical and other genital cancers. We evaluated the prevalence of HPV DNA in the oral cavity/oropharynx in a cross section of children aged 2 weeks to 20 years. METHODS: A risk factor questionnaire and oral exfoliated cells were collected from children (N = 1235). HPV DNA was detected using PCR, dot blot hybridization, and DNA sequencing. RESULTS: The HPV prevalence was 1.9% in the oral cavity/oropharynx of children. A bimodal age distribution was observed with the highest HPV prevalence in the youngest and oldest groups: 2.5% aged <1 year, 0.8% aged 1 to 4 years, 1.2% aged 5 to 11 years, 1.5% in aged 12 to 15 years, and 3.3% in aged 16 to 20 years. The prevalence of the HPV quadrivalent vaccine types (HPV-6, 11, 16, 18) reached 0.9% in the 16- to 20-year age group. In this age group, female gender [odds ratio (OR): 6.9, P = 0.04], genital warts (OR: 19.3, P < 0.01), and current smoker (OR: 6.5, P = 0.01) were associated with a higher risk of being detected with an oral HPV infection. No risk factors in parents were identified with transmission of HPV to infants. CONCLUSIONS: The age specific prevalence rates of HPV in this large cross section of children and adolescents demonstrate that HPV infection is acquired gradually in childhood. These data support a target age for HPV vaccination before puberty to prevent serious HPV-related genital and oral diseases. PMID- 17721382 TI - Ventilator-associated pneumonia (VAP) in pediatric intensive care units. PMID- 17721384 TI - Value of Toxoplasma gondii detection in one hundred thirty-three placentas for the diagnosis of congenital toxoplasmosis. AB - The placenta examination by polymerase chain reaction and mouse inoculation increased the sensitivity of the diagnosis of congenital toxoplasmosis at birth from 60% (use of serologic techniques on the newborn's blood only) to 75% (both serologic techniques and placental analysis). The specificity of Toxoplasma gondii detection in the placenta was 94.7%. PMID- 17721385 TI - Slow progression of human immunodeficiency virus and hepatitis C virus disease in a cohort of coinfected children. AB - We carried out a retrospective study to determine the evolution of 23 vertically HIV-1/HCV coinfected children and 30 vertically HIV-1 infected children (control group). Six out of 23 HIV-1/HCV coinfected children developed AIDS versus 20 out of 30 HIV-1 children (P < 0.05). HIV-1/HCV children had a good evolution in relation to CD4 and HIV-RNA viral load. They presented higher CD8 counts than HIV 1 children during long periods, and slower progression of HCV liver disease. PMID- 17721386 TI - Ultrasound measurement of gallbladder wall thickening as a diagnostic test and prognostic indicator for severe dengue in pediatric patients. AB - Gallbladder wall thickening measured by ultrasound was significantly associated with severe dengue, as well as with hallmark features of thrombocytopenia and elevated hematocrit/hemoconcentration, in children with suspected dengue in Nicaragua. We demonstrate that gallbladder wall thickening serves as a clinically relevant diagnostic test and prognostic indicator of severe dengue in pediatric populations. PMID- 17721387 TI - No decrease in clindamycin susceptibility despite increased use of clindamycin for pediatric community-associated methicillin-resistant Staphylococcus aureus skin infections. AB - A previous study at our institution revealed 98% of methicillin-resistant Staphylococcus aureus (MRSA) isolates were susceptible to clindamycin; however, beta-lactams were then the predominant empiric treatment. This follow-up chart review study examined subsequent staphylococcal skin and soft tissue infection treatment and susceptibility patterns over a 2-year period. Of 296 S. aureus skin and soft tissue infections, 73% were MRSA, of which 87% were community-associated MRSA; MRSA infections peaked in warm summer months. Despite a significant increase in empiric clindamycin use, 97% of community-associated-MRSA isolates retained susceptibility to clindamycin. PMID- 17721388 TI - Efficacy and safety of caspofungin for the empiric management of fever in neutropenic children. AB - This retrospective review evaluates the response to caspofungin when given to children with febrile neutropenia and describes adverse effects attributable to caspofungin, including risk of hepatotoxicity during concomitant therapy with cyclosporine. Sixty-seven courses of caspofungin administered to 56 patients (1 17 years) were surveyed; 53 (79%) courses resulted in an overall favorable response. Ten children (15% of courses) experienced an adverse drug-related event that was probably or possibly attributable to caspofungin. Rash and hypokalemia were the most commonly identified adverse effects. One of 19 children receiving caspofungin and cyclosporine concurrently developed hepatotoxicity possibly related to caspofungin. PMID- 17721389 TI - Propionibacterium acnes endocarditis in an adolescent boy suffering from a congenital cardiopathy. AB - Propionibacterium acnes endocarditis is an uncommon infection in pediatrics. We describe a case of P. acnes endocarditis in a 16-year-old boy that occurred 6 months after recurrent surgery for a congenital cardiopathy. Molecular identification of P. acnes was obtained. He recovered from this infection after a surgical treatment and with a prolonged antibiotic regimen including ceftriaxone. PMID- 17721390 TI - Nocardia farcinica isolated from bronchoalveolar lavage fluid of a child with cystic fibrosis. AB - Nocardia spp. can cause pulmonary infection, usually in the setting of immunosuppression or underlying lung disease. There have been a few reports of these organisms isolated from cystic fibrosis patients and, when recovered, the isolates were almost always Nocardia asteroides. We present the first reported case of a child with cystic fibrosis harboring Nocardia farcinica. PMID- 17721391 TI - Encephalopathy complicated by Guillain-Barre syndrome and hydrocephalus and associated with acute Bartonella quintana infection. AB - We describe a 16-month-old girl who suffered from encephalopathy leading to intensive care unit hospitalization, complicated by Guillain-Barre syndrome and hydrocephalus, and who had serologic and molecular evidence of central nervous system infection by B. quintana. The possible association of B. quintana with Guillain-Barre syndrome and hydrocephalus has not been previously described and demonstrates the growing spectrum of neurologic complications of Bartonella spp. infections. PMID- 17721392 TI - Xylitol to prevent acute otitis media. PMID- 17721393 TI - Continuous intrathecal interferon alpha application in subacute sclerosing panencephalitis. PMID- 17721395 TI - Rapid and durable antiretroviral effect of the HIV-1 Integrase inhibitor raltegravir as part of combination therapy in treatment-naive patients with HIV-1 infection: results of a 48-week controlled study. AB - BACKGROUND: Raltegravir is an HIV-1 integrase strand-transfer inhibitor with potent in vitro activity. This study explored the antiretroviral activity and safety of raltegravir in treatment-naive patients with plasma HIV-1 RNA levels > or = 5000 copies/mL and CD4 T-cell counts > or = 100 cells/mm. METHODS: Multicenter, double-blind, randomized, controlled study of raltegravir at doses of 100, 200, 400, and 600 mg twice daily versus efavirenz at a dose of 600 mg/d, all in combination with tenofovir at a dose of 300 mg/d and lamivudine at a dose of 300 mg/d (clinicaltrials.gov identifier: NCT00100048). RESULTS: In the 198 patients treated (160 on raltegravir and 38 on efavirenz), the mean HIV-1 RNA level ranged from 4.6 to 4.8 log10 copies/mL at baseline. At weeks 2, 4, and 8, the proportion of patients achieving an HIV-1 RNA level <50 copies/mL was greater in each of the raltegravir treatment groups than in the efavirenz group. By week 24, all treatment groups appeared similar, with plasma HIV-1 RNA levels <400 copies/mL in 85% to 98% of patients and <50 copies/mL in 85% to 95% of patients. These reductions were maintained through week 48 in 85% to 98% of patients and in 83% to 88% of patients, respectively. Five (3%) patients on raltegravir and 1 (3%) on efavirenz experienced virologic failure before week 48. Drug-related clinical adverse events were less common with raltegravir than with efavirenz. After 24 and 48 weeks of treatment, raltegravir did not result in increased serum levels of total cholesterol, low-density lipoprotein cholesterol, or triglycerides. CONCLUSIONS: Raltegravir at all doses studied was generally well tolerated in combination with tenofovir and lamivudine. Raltegravir exhibited potent and durable antiretroviral activity similar to that of efavirenz at 24 and 48 weeks but achieved HIV-1 RNA levels below detection at a more rapid rate. PMID- 17721396 TI - Magnetic resonance spectroscopy of hepatic lipid content and associated risk factors in HIV infection. AB - BACKGROUND: Liver-related illness is increasingly recognized as a source of morbidity in HIV-infected patients. Fatty infiltration of the liver is potentially an important consequence of HIV and treatment with antiretroviral (ARV) therapy. OBJECTIVE: The aim of the present study was to evaluate HIV infected men and women for hepatic steatosis using noninvasive magnetic resonance spectroscopy (MRS) and to assess the relationship between liver fat content, insulin resistance, and other associated risk factors. METHODS: We examined 33 consecutively recruited HIV-infected adults without specific referral for liver disease. Subjects with alcohol abuse within 3 years or end-stage liver disease were excluded. The primary clinical measures were hepatic fat content measured by MRS, homeostasis model for assessment of insulin resistance (HOMA-IR), and body fat distribution assessed by cross-sectional computed tomography. RESULTS: We identified hepatic steatosis (liver fat content > or =5%) in 42% of subjects. Hepatic fat content was significantly correlated with HOMA-IR (r = 0.68, P < 0.0001) and increased visceral adiposity (r = 0.60, P < 0.001). Subjects with steatosis had significantly increased body mass index and alanine aminotransferase and triglyceride levels, with lower muscle attenuation (ie, increased intramuscular fat) compared to subjects without steatosis. However, steatosis was not related to duration of HIV, ARV exposure, or HCV coinfection. CONCLUSIONS: These data suggest that hepatic steatosis may be very common in HIV, not limited to those with HCV coinfection, and may play an important role in the metabolic profile among HIV-infected men and women. PMID- 17721397 TI - Mental health and disclosure of HIV status in Zambian adolescents with HIV infection: implications for peer-support programs. AB - OBJECTIVES: To examine emotional and behavioural difficulties in HIV positive Zambian adolescents and to determine the relationship between disclosure of HIV status and mental health. DESIGN: A cross-sectional survey. METHODS: Participants were 127 HIV positive adolescents aged 11 to 15 years recruited through clinics in the Lusaka region. Mental health was assessed using the youth report version of the Strengths and Difficulties Questionnaire (SDQ). Caregivers completed the parent SDQ. Sixty-two participants were invited for a semi-structured interview which probed views on attending a peer support group. RESULTS: Compared to a British community sample participants had increased mental health problems (OR, 2.1), particularly emotional symptoms (OR = 3.6) and peer problems (OR = 7.1). The majority of children (n = 94) were receiving antiretroviral (ARV) treatment, but only 48 children (37.8%) had their HIV status disclosed. Those who had not had their HIV status disclosed were younger (P < 0.001) and less likely to be receiving ARV treatment (P < 0.001). Controlling for these factors they were also more likely to score in the abnormal range of the emotional difficulties subscale (OR = 2.63, 95% CI: 1.11 to 6.26). Of 38 interviews transcribed, content analysis showed that only 3 children were opposed to participation in a peer-group program, with the majority (23/38) expressing reasoned and positive responses, regardless of disclosure status. CONCLUSION: High rates of emotional and peer problems were found in this sample but disclosure of HIV status did not have a negative effect on mental health. Interventions to promote disclosure could facilitate access to emotional and peer support. PMID- 17721398 TI - Rethinking approaches to risk reduction for injection drug users: differences in drug type affect risk for HIV and hepatitis C virus infection through drug injecting networks. AB - OBJECTIVE: To identify and compare the drug-injecting network characteristics of cocaine and heroin injectors associated with a risk of HIV and hepatitis C virus (HCV). METHODS: Active injectors were recruited from syringe exchange and methadone programs. Characteristics of all participants and their social networks were elicited. Regression analysis using generalized estimating equations examined the network characteristics of injection drug users (IDUs) relative to cocaine or heroin use in the past 6 months. RESULTS: Of 282 IDUs, 228 (81%) used cocaine and 54 (19%) used heroin as their primary injected drug. In analyses adjusted for age and gender, cocaine injectors compared with heroin injectors were more likely to live in unstable housing (odds ratio [OR] = 3.55, 95% confidence interval [CI]: 1.49 to 8.40), self-report HCV infection (OR = 4.69, 95% CI: 2.14 to 10.31), and have a greater number of IDUs in their social network (OR = 1.61, 95% CI: 1.14 to 2.28) and were less likely to be polydrug users (OR = 0.06, 95% CI: 0.02 to 0.16) and to have social support (OR = 0.97, 95% CI: 0.95 to 0.99). The injecting networks of cocaine users were more likely to have members who were older (OR = 1.08, 95% CI: 1.04 to 1.12), had a history of shooting gallery use (OR = 2.27, 95% CI: 1.08 to 4.76), and had shorter relationships with the subject (OR = 0.91, 95% CI: 0.85 to 0.97). CONCLUSIONS: Beyond personal behaviors, HIV and HCV infection risk seems to be linked to social network traits that are determined by drug type. Prevention efforts to control the spread of bloodborne viruses among IDUs could benefit from tailoring interventions according to the type of drug used. PMID- 17721399 TI - Negative social impacts among volunteers in an HIV vaccine efficacy trial. AB - OBJECTIVE: Describe the negative social impacts (NSIs) and their predictors in an HIV vaccine efficacy trial. METHODS: Volunteers in the North American phase 3 trial of AIDSVAX B/B vaccine were questioned semiannually about NSIs. Multivariable logistic models identified independent predictors of NSI reporting. RESULTS: Of 5417 volunteers (94% male), 18% reported at least 1 NSI. Most events occurred early during trial participation and involved concerns by family and friends that the volunteer was HIV-infected or at risk for infection. Problems with disability/life insurance and employment occurred less frequently (<1%). Individuals who became HIV-infected reported NSIs similar to HIV-negative volunteers. In multipredictor analysis of male volunteers, NSI reporters were younger (adjusted odds ratio [OR(Adj)] = 1.6, 95% confidence interval [CI]: 1.2 to 2.1 and OR(Adj) = 1.4, 95% CI: 1.1 to 1.8 for ages 18 to 25 years and 26 to 35 years vs. > or =46 years, respectively), enrolled at sites with 50 or fewer volunteers (OR(Adj) = 2.3, 95% CI: 1.7 to 3.1), or lived in cities with high AIDS case rates (OR(Adj) = 1.4, 95% CI: 1.1 to 1.8). CONCLUSIONS: A modest proportion of vaccine efficacy trial volunteers reported problems in interpersonal relationships from trial participation. Serious harms involving insurance and employment were rare. Strategies to prevent harm from disclosure, particularly for younger volunteers and those from high seroincidence sites, may reduce NSIs in future trials. PMID- 17721400 TI - How homosexual men believe they became infected with HIV: the role of risk reduction behaviors. AB - OBJECTIVES: A range of HIV risk reduction strategies has been described in homosexual men who practice unprotected anal intercourse (UAI), including serosorting, strategic positioning, and negotiating around an HIV-positive partner's viral load. It is uncertain how commonly these behaviors might result in HIV infection. We describe sexual behaviors and associated risk reduction strategies reported by homosexual men in their accounts of their recent seroconversion. METHODS: Homosexual men recently diagnosed with primary HIV infection between 2003 and 2006 were invited to participate in a nurse administered survey. RESULTS: Among 158 men enrolled, 143 (91%) were able to identify the high-risk event that they believed led to their HIV seroconversion, and this involved UAI in 102 (71%). Among these 102 men, 21 (21%) reported they were certain that the source partner was HIV-negative. Ten men (10%) reported insertive UAI as the highest risk behavior. Of the 21 men who reported knowing the HIV-positive partner's viral load, 9 reported that the man had an undetectable viral load (43%). CONCLUSION: In 38% of the high-risk events involving UAI, infection occurred when the reported risk event involved serosorting, strategic positioning, or intercourse with a man whose viral load was believed to be undetectable. PMID- 17721401 TI - Cerebrospinal fluid leak after anterior cervical disc fusion: an unusual cause of dysphagia and neck mass. AB - OBJECTIVE: Dysphagia after anterior cervical disc fusion (ACDF) is a common complaint. We present two cases of dysphagia caused by a rare complication after ACDF: cerebrospinal fluid (CSF) leak into the neck. STUDY DESIGN: A case series of two patients. METHODS: Both patients underwent a chart review, comprehensive history, physical examination, flexible nasolaryngoscopy, and radiographic imaging. A literature review of the MEDLINE database (1966-2006), using key words "dysphagia" and "anterior discectomy," was performed. RESULTS: We present two patients with persistent dysphagia after ACDF surgery caused by CSF leak into the neck. Their clinical presentation, physical and radiographic examination findings, and hospital course will be discussed. CONCLUSIONS: CSF collection presenting as dysphagia and neck mass after ACDF must be included in the differential diagnosis because incision and drainage is contraindicated, and fine needle aspiration (FNA) must be performed under sterile conditions. Treatment including lumbar drain or re-exploration is appropriate. PMID- 17721403 TI - Cadaveric and engineering analysis of the septal L-strut. AB - OBJECTIVES: To identify patterns of failure of the L-strut, to identify elements of the nasal framework that support the L-strut, and to investigate the effect of altering L-strut design on its stability. STUDY DESIGN: Laboratory study with human cadaveric heads and computational modeling. METHODS: Directional forces were applied to cadaveric L-struts and patterns of failure with incremental force were noted. Computational modeling using the finite element method (FEM) was employed to determine quantitatively the effect of various modifications on the stability of the L-strut. RESULTS: The L-strut was found to respond to frontal force initially by buckling. This buckling was reversible until the force exceeded a certain threshold when the L-strut broke at the bony-cartilaginous junction. The threshold force varied depending on the length of the overlap with the bony vault. Intact mucoperichondrium provided significant stability. Modeling with FEM showed that the preservation of a triangular piece of cartilage at the dorsal anchor of a narrowed L-strut can offset some of the loss in mechanical stability. CONCLUSIONS: Intrinsic elasticity of the septal cartilage, the mucoperichondrial flap, and overlap with the bony vault all contribute to the stability of the L-strut, which is enhanced by preserving a small segment of cartilage at the bony-cartilaginous junction of the dorsal L-strut. PMID- 17721402 TI - Comparison between mitomycin C and chitosan for prevention of anterior glottic steno after CO2 laser cordectomy in dogs. AB - OBJECTIVE: To compare the effectiveness of an immediate application of topical mitomycin C (MMC) with chitosan for prevention of anterior glottic stenosis (AGS) after microsurgical resecting of both vocal fold with CO2 laser, including the anterior commissure, in a canine model. DESIGN: Prospective randomized experimental study. METHOD: Twenty-four canine larynges were injured by a microresecting procedure of both vocal folds with a CO2 laser. The dogs were randomly divided into three groups for treatment, respectively with MMC, chitosan, or isotonic sodium chloride solution (control) for 5 minutes immediately after surgery. One week after the initial surgery, three dogs in each group were randomly selected, the ultrastructures of the fibroblasts were examined with a transmission electronic microscope, and expression of basic fibroblast growth factor (bFGF) and transforming growth factor beta1 (TGF-beta1) were evaluated by enzyme-linked immunosorbent assay (ELISA). Three weeks after surgery, the remaining dogs' glottic web were lysed and repeatedly treated with MMC, chitosan, or isotonic sodium chloride solution. The glottic wound healing and AGS formation were examined every week, and all larynges were harvested and examined histologically 6 weeks after the initial surgery. RESULTS: Results included 1) transmission electronic microscope examination of the ultrastructures of the fibroblasts indicated that both MMC and chitosan inhibited the proliferation of fibroblast; 2) the expression of bFGF and TGF-beta1 increased both in the MMC group and the chitosan group, and the expression of bFGF in the chi-tosan group was higher than in the MMC group (P = .010), while the expression of TGF-beta1 was lower (P = .000);3) the extent of AGS formation was decreased both in the MMC group and the chitosan group, while it was less in the chitosan group than in the MMC group (P = .047); 4) the grade of collagen content between the MMC group and the chitosan group was not significantly different (P = .5). CONCLUSION: Chitosan is more effective in preventing AGS after CO2 laser cordectomy than MMC. PMID- 17721404 TI - Minimally invasive endoscope-assisted parotidectomy: a new approach. AB - OBJECTIVE: To evaluate the benefits of a new approach, endoscopic parotidectomy through a postauricular skin incision by using an ultrasonically activated scalpel. STUDY DESIGN: An investigation of the outcome of endoscopic parotidectomy at a tertiary referral medical center. METHODS: Fourteen operations for selected patients presenting with benign parotid tail disease were performed via minimally invasive endoscopic resection by a single surgeon (MK Chen). RESULTS: All 14 operations were successfully performed endoscopically, and no conversions to conventional open resection were necessary. The procedures lasted 60 to 160 minutes. Two patients had transient grade II facial paresis. The scars were almost invisible due to their concealed location behind the ear. CONCLUSIONS: Minimally invasive endoscope-assisted parotidectomy is a feasible method for treatment of benign lesions located in the parotid tail. The main advantage of this procedure is that the small operative scar is concealed in the postauricular area resulting in improved cosmetic results. PMID- 17721405 TI - Gene expression changes of inflammatory mediators in posterior laryngitis due to laryngopharyngeal reflux and evolution with PPI treatment: a preliminary study. AB - HYPOTHESIS: Standard of care in laryngopharyngeal reflux (LPR) is acid suppression therapy. Its treatment efficacy and mechanism of action are not well documented. No objective study investigating the molecular patterns of inflammation in LPR or in response to proton pump inhibitor (PPI) treatment has been accomplished. We hypothesized that gene expression levels of mediators of inflammation -- interleukin 6 (IL6), interleukin 8 (IL8), interleukin 1a (IL1a), interleukin 1b (IL1b), transforming growth factor beta 1 (TGFbeta1), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF2), and tumor necrosis factor alpha (TNFalpha) -- in posterior larynx tissue would be increased in those with diagnosed LPR and would be then reduced with PPI treatment. STUDY DESIGN: Prospective uncontrolled trial. METHODS: Biopsies from the posterior larynx were taken from 25 participants with LPR before and after a 10-week period with rabeprazole (40 mg). RNA isolation and real-time PCR was used to measure gene expression levels. RESULTS: No significant differences were measured for any of the cytokines, either for the entire participant group (n = 25) or for the subset of participants who did not have a previous history of PPI usage (n = 15). In those participants who had a history of PPI usage (n = 10), a significant increase in gene expression levels post medication was measured for TGFbeta1 (P = .0396), VEGF (P = .0216), IL8 (P = .0297), after adjusting for compliance, subjective improvement, and reflux severity. CONCLUSIONS: Our findings are provocative and speak to the unresolved understanding of the pathophysiology of LPR, its diagnosis, and its differences from gastroesophageal reflux disease. PMID- 17721406 TI - Adenotonsillectomy for obstructive sleep apnea in children: outcome evaluated by pre- and postoperative polysomnography. AB - OBJECTIVE: To evaluate the outcome of adenotonsillectomy for obstructive sleep apnea (OSA) in children using objective data from polysomnography supplemented by subjective proxy reports from the OSA-18 quality of life instrument. STUDY DESIGN: Prospective cohort study. METHODS: Children 3 to 14 years of age with OSA diagnosed principally on the basis of polysomnography as having an obstructive apnea/hypopnea index (AHI) of 5 or greater underwent adenotonsillectomy. OSA was classified as mild (AHI > or = 5 < 10), moderate (AHI > or = 10 < 20), or severe (AHI > or =20). Children enrolled in the study also had postoperative polysomnography 3 to 6 months after surgery. Caregivers completed the OSA-18 survey before surgery and within 6 months after surgery. Pearson correlation was used to compare the pre- and postoperative AHI values with the pre- and postoperative OSA-18 total scores. SAS procedures (SAS Corp., Cary, NC) were used for statistical analyses. A P value less than or equal to .05 was considered significant. RESULTS: The study population included 79 healthy children, 40 of who were male. The mean age was 6.3 (range, 3.0-14.0) years. Only tonsillar size was correlated significantly with a high preoperative AHI. For all children, the preoperative AHI value was higher than the postoperative value. The mean preoperative AHI for the study population was 27.5, whereas the mean postoperative AHI was 3.5. This change was highly significant (P < .001). The percentage of children with normal polysomnography parameters after adenotonsillectomy ranged from 71% to 90% as a function of the criteria used to define OSA. It was highest when an obstructive apnea index less than 1 was used and lowest when an AHI less than 1 was used to define resolution of OSA. Overnight respiratory parameters after adenotonsillectomy were normal for all children with mild OSA. Three (12%) children with moderate preoperative OSA, and 13 (36%) children with severe preoperative OSA had persistent OSA after adenotonsillectomy. Resolution of OSA occurred in all children with a preoperative AHI less than or equal to 10 and in 73% of children with a preoperative AHI greater than 10. The mean total OSA-18 score and the mean scores for all domains showed significant improvement after surgery (P < .001). The preoperative AHI values had a fair correlation with the preoperative total OSA-18 scores (r = 0.28), but postoperative AHI values had a poor correlation with the postoperative total OSA-18 scores (r = 0.16). Caregivers reported snoring some, most, or all of the time in 22 (28%) children; this group included all children with persistent OSA. CONCLUSIONS: Adenotonsillectomy for OSA results in a dramatic improvement in respiratory parameters as measured by polysomnography in the majority of healthy children. Quality of life also improves significantly after adenotonsillectomy for OSA in children. However, the correlation between improvements in respiratory parameters and improvements in quality of life is poor. Severe preoperative OSA is associated with persistence of OSA after adenotonsillectomy. Postoperative reports of symptoms such as snoring and witnessed apneas correlate well with persistence of OSA after adenotonsillectomy. PMID- 17721408 TI - Medical missions to Vietnam and Cuba: lessons in global education. PMID- 17721407 TI - Reliability of the Welling scale (WS1) for rating temporal bone dissection performance. AB - OBJECTIVE: To determine the inter- and intrarater reliability of using a new scale (Welling scale) for resident evaluation of temporal bone dissection performance. STUDY DESIGN: Prospective, double-blinded, randomized trial. METHODS: Twelve residents in otolaryngology (postgraduate year [PGY] 2-5) drilled 26 temporal bones (21 cadaveric, 5 plastic) with the objective to perform a complete mastoidectomy with facial recess approach. These bones were then rated using the Welling scale by six independent raters on two separate occasions (4-6 wk apart). Raters were blinded to PGY year. The Kappa statistic was calculated for inter- and intrarater reliability. RESULTS: Intrarater agreement was high for all raters, ranging from kappa = 0.65 to 0.72 (all P < .001), whereas the interrater agreement scores were more moderate (range, kappa = 0.49-0.64; all P < .01). CONCLUSION: The Welling scale can be used reliably to assess temporal bone dissection performance where performance is measured by assessment of end product (mastoidectomy with facial recess approach). PMID- 17721409 TI - Expression of vascular endothelial growth factor and basic fibroblast growth factor in sporadic vestibular schwannomas correlates to growth characteristics. AB - HYPOTHESIS: Expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) may have an impact on the growth characteristics of sporadic vestibular schwannomas (VSs). BACKGROUND: Vestibular schwannoma is a benign, slow-growing neoplasm that accounts for 6% of all intracranial tumors. The biological backgrounds for neoplastic growth and especially for the various growth patterns of VS remain largely unknown. Because several angiogenic and cytotrophic factors have been described to be involved in the growth of malignant tumors, we initiated this study to examine 2 major representatives of such growth factors in VS and their possible correlation to the growth characteristics of sporadic VSs. METHODS: Surgical specimens from 17 patients with sporadic VS were examined, and the expression of 2 major angiogenic and neurotrophic factors, bFGF and VEGF, was quantitatively analyzed at the mRNA and protein levels. The microvessel density (MVD) was defined by CD31 staining. RESULTS: All tumors showed expression of bFGF and VEGF at both the mRNA and protein levels. The mRNA expression and the protein expression of both growth factors correlated positive to tumor volume, to tumor growth index, and to MVD. CONCLUSION: The bFGF and VEGF mRNA expression and the bFGF and VEGF protein expression in sporadic VS correlates to the tumour volume, to the tumor growth index, and to the MVD. This might indicate an angiogenic and neurotrophic influence of these factors and a possible involvement in the growth of sporadic VS. PMID- 17721411 TI - Posterior petrous face meningiomas: an algorithm for surgical management. AB - OBJECTIVE: The objective of the present study was to report our surgical strategy in the management of 81 patients with posterior petrous face meningiomas. STUDY DESIGN: Retrospective study. SETTING: This study was conducted at a quaternary private otology and cranial base center. PATIENTS: Of 139 patients with posterior fossa meningioma, 81 occurred on the posterior petrous face of the temporal bone and were the object of this study. INTERVENTIONS: Thirty-one patients were approached by the enlarged translabyrinthine approach. The enlarged translabyrinthine approach with transapical extension Type II was performedin 29 patients. The combined retrosigmoid-retrolabyrinthine approach was chosen in 8 cases. The modified transcochlear approach Type A with permanent posterior transposition of the facial nerve (FN) was performed in 6 patients. Two patients underwent a retrolabyrinthine subtemporal transapical approach. One patient underwent a transpetrous middle cranial fossa approach. Four patients with intracanalicular meningiomas were operated on through the enlarged middle cranial fossa approach. RESULTS: Total removal of the tumor (Simpson Grades I and II) was achieved in most patients (92.5%). The FN was anatomically preserved in 79 of the 81 (97.5%) patients. Five patients had less than 1 year follow-up, and 2 patients were lost to follow-up and were excluded in evaluation of the final FN outcome. At 1-year follow-up, 46 patients (63%) had Grade I to II, 19 (26%) had Grade III, 4 (5.4%) had Grade IV, 1 (1.3%) had Grade V, and 3 (4.1%) had Grade VI. Hearing preserving surgery was attempted in 15 patients (18.5%) with preoperative serviceable hearing. Of these 15 patients, 11 had their hearing preserved at the same preoperative level, and 4 experienced postoperative deafness. Postoperatively, a new deficit of 1 or more of the lower cranial nerves was recorded in 3 patients. One patient experienced subcutaneous cerebrospinal fluid collection that required surgical management. CONCLUSION: Total tumor removal (Simpson Grades I-II) remains our treatment of choice and takes priority over hearing preservation. Subtotal resection is indicated for older and debilitated patients with giant lesions to relieve the tumor compression on the cerebellum and brainstem. Subtotal removal is also preferred in the face of the absence of a plane of cleavage between the tumor and the brainstem, in the presence of encasement of vital neurovascular structures, in elderly patients with tumors adherent to preoperatively normal facial or lower cranial nerves. PMID- 17721420 TI - Incorrect osteosynthesis as a cause of bone union disturbances. AB - BACKGROUND: Treatment of bone union disturbances is one of the most difficult therapeutic challenges in any orthopaedic and trauma department. MATERIAL AND METHODS: An analysis of causes of bone union disturbances in a series of 136 patients treated between 1999 and 2005 at the Orthopaedics and Traumatology Department of Jagiellonian University's Collegium Medicum is presented with particular regard to the type of primary stabilisation. RESULTS: An inappropriate primary stabilisation technique was the cause of bone union disturbances in nearly all of the patients. All errors identified in the series, such as wrong classification of fracture, failure to account for fracture biomechanics, wrong implant choice, incorrect reduction of bone fragments, wrong implant positioning and brutal surgery technique, were associated with primary stabilisation of the fractures. CONCLUSIONS: 1. Operator errors committed during primary fracture stabilization are the most common cause of bone union disturbances. 2. Elimination of errors committed during primary stabilization is the most effective prophylaxis of bone union disturbances. PMID- 17721419 TI - Current opinion about using the platelet-rich gel in orthopaedics and trauma surgery. AB - The use of growth factors in combination with tissue engineering seems to be the most promising method in the future for the treatment of tissue, bone and cartilage defect. Growth factors are cytokines with regulatory functions for healing in tissues of the musculoskeletal system. These small peptides are synthesised by resident cells at the site of injury such as mesenchymal stem cells and chondrocytes, or by the infiltrating inflammatory process. Platelet rich plasma (PRP) is a novel osteoinductive therapeutic approach that is increasingly used in treatment of such complications of bone healing processes. The activator for PRP is a mixture of thrombin and calcium chloride. After connecting these substances platelet-rich gel (PRG) is formed and numerous regulatory molecules to the injury site such as PDGF, TGF-, VEGF, IGF, EGF and antimicrobial proteins are released. The aim of this article is presentation of present knowledge about properties and possibilities of using platelet-rich plasma in the treatment of soft tissue and bone healing disturbances. PMID- 17721421 TI - Evaluation of nonunions of the tibia diaphysis - own experience. AB - BACKGROUND: Delayed union is not an expected outcome of treatment of a bone fracture. The cause of the delayed union must be established before treatment of the complication can be undertaken. The method of treatment depends mainly on the specific nature of delayed bone union. The study evaluates the causes of delayed bone union during treatment of tibial shaft fractures. MATERIAL AND METHODS: Seventy-two patients with delayed union following a fracture of the tibial diaphysis were treated in the Department of Orthopaedics and Musculoskeletal Traumatology of Wroclaw Medical University between 1995 and 2005. All patients had received previous treatment of the fractures. Depending on the morphology of the delayed union, the treatment was with Ilizarov's compression-distraction method or autologous osteoplasty with intramedullary, internal or external fixation. The choice of a method was based on an analysis of the features of the non-union while fracture morphology, presence of other concomitant sequelae of the original injury, fixation method and possible surgical errors, post-operative patient management, co-morbidity and patient compliance were evaluated as risk factors of delayed bone union. The risk factors were subdivided into treatment dependent (external) and treatment-independent (internal). Treatment outcomes were evaluated on the basis of an orthopaedic examination and radiographic evidence. RESULTS: In the vast majority of patients, delayed union of the tibial diaphysis was due to external factors. CONCLUSIONS: Delayed union of the tibia can be avoided through early and simultaneous treatment of all sequelae of the original trauma. Patient management must be based on state-of-the-art medical knowledge. PMID- 17721422 TI - Nine-years experience with the use of shock waves for treatment of bone union disturbances. AB - BACKGROUND: Stimulation of bony union by means of various physical modalities has not been widely used in clinical practice. Extracorporeal shock wave therapy (ESWT) offers the most promise. ESWT was first used to crush kidney stones (lithotripsy) in 1980. It is based on a sound rationale. Shock waves penetrate soft tissues and to release mechanical energy at the surface of bone, producing microfractures in sclerotic bone ends and triggering physiologic fracture healing, or "healing of fracture without a fracture". MATERIAL AND METHODS: Since 1998 we have treated more than 150 patients with delayed and non-unions of fractures using a standard lithotripter. Between 1,500 and 3,000 pulses were generated during one procedure depending on fracture size. Treatment effects were typically seen in the first follow-up radiographs at 6-12 weeks. RESULTS: Fracture union was achieved in 83% of the patients after 3-6 months. No complications were noted. The method arguably represents a useful adjunct to the treatment of bone union disturbances. It is a method of choice for patients with non-dislocated bony fragments. It can be used with metal implants or immobilisation in a cast or brace. In patients with dislocated bony fragments, we used the Ilizarov apparatus for correction and compression and shock waves for stimulation of healing. The best results were observed in delayed unions and vital nonunions. Atrophic nonunions did not respond well. Large bone defects did not fill. CONCLUSIONS: Shock wave therapy is a very effective treatment for delayed union or non-union of bone. It is a safe and complication-free method. ESWT should be considered in every case of delayed union. It may help avoid surgery under favourable conditions. PMID- 17721423 TI - Own clinical experience with functional bracing for treatment of pseudarthrosis and delayed union of the tibia. AB - BACKGROUND: Functional bracing is a proven method of treatment of tibial fractures. Since 1998 we use individually produced braces made of "combicast" according to Schuren technique. The brace greatly limits the angulation and displacement allowing the axial compression, promoting the physiology of fracture healing. MATERIAL AND METHODS: Functional bracing was applied in 51 patients, ageing from 18 top 69 years. The conservative treatment was previously performed in 16 patients, and 35 patients were treated surgivcally (from 1 to three surgeries in other centers). The delayed union was diagnosed in 28 patients - no signs of bone healing after 4 months after fracture. In 23 patients the pseudarthrosis of tibia was diagnosed after 6 months of treatment. In 9 patients shock wave therapy or bone marrow injection was additionally performed. RESULTS: In all 35 patients, but one, who were treated only with the use of functional bracing, the bone consolidation, after 4 to 12 months of treatment was obtained. In cases with delayed union the fast normalization of blood circulation with subsidence of swelling and fast restoration of rang of the joints motion was observed. X-ray reveals fracture healing with disappearing of local osteoporosis. The patients feel comfortable and require only minimal rehabilitation. Biological stimulation can be achieved by means of shock waves or bone transplantation. No complication according to the functional brace was noted. CONCLUSIONS: This safe and economic method constitues an important aid in treatment of non only acute but also of complicated tibial fractures. PMID- 17721424 TI - Heterotopic ossification in patients after total hip replacement. AB - Heterotopic ossification (HO) is defined as pathological bone formation in soft tissues, for example in muscles, where physiologically there is no osseous tissue present. It is one of the most common complications of total hip joint replacement surgery. A wide variety of risk factors for heterotopic ossification have been identified to date. Almost 90% of total hip arthroplasty patients are at high risk for HO. There are two primary methods of preventing heterotopic ossification: pharmacotherapy with NSAIDs (non steroid anti-inflammatory drugs) and radiotherapy. Symptomatic heterotopic ossifications are treated by extracorporeal shock wave therapy (ESWT) and surgery, followed by NSAID pharmacotherapy or radiotherapy. The arterioles adjacent to areas of heterotopic ossification are usually embolized prior to the operation. This article describes the state of the art in the prevention and treatment of heterotopic ossifications based on the available literature. PMID- 17721425 TI - New technique of surgical treatment of malignant calcaneal tumours. Preliminary report. AB - BACKGROUND: Malignant tumours of the calcaneus are very rare among children, constituting up to 3% of all bone tumours. This paper presents the outcome of a new technique of surgical treatment of malignant calcaneal tumours in the paediatric population involving the use of a large frozen allogeneic graft of the head of femur with a fragment of the femoral neck. MATERIAL AND METHODS: Three patients were treated for primary malignant tumours of bone at our Department. The surgery was preceded by induction chemotherapy. A skin incision was made on the medial aspect of the foot. After the dissection of the calcaneus together with the tumour (Ennecking's wide resection), the defect was reconstructed with a frozen allogeneic bone graft. The graft was modelled and attached to the tarsal bone using metal clasps (arthrodesis). The Achilles tendon was also attached to the graft with metal clasps. A Redon suture was left in the floor of the wound. Single-layer sutures were placed in subcutaneous tissue and skin. The limb was immobilized in thigh plaster with the foot in 900 dorsiflexion. RESULTS: The wound healed by first intention. Early post-operative complications were not observed, except for transient oedema of the surrounding tissues. The flexion and dorsiflexion movements were partially preserved. Local radical excision of the tumour was achieved in all the children. The graft healed into place. The patients are able to move without aid. CONCLUSIONS: The use of a large allogeneic bone graft of the head of femur after excision of the calcaneus can assure very good long-term functional outcomes. PMID- 17721426 TI - Effectiveness of botulinum toxin A in the treatment of spasticity of the lower extremities in adults - preliminary report. AB - BACKGROUND: Botulinum toxin (BTX is currently a recognised treatment for local spasticity, especially in children with cerebral palsy. The following paper presents the early result of BTX treatment for adult patients with spastic paresis of the lower limbs. MATERIAL AND METHODS: Twenty adult paraplegic patients (mean age 42 years) following cervical or thoracic SCI or suffering from MS, with moderate-to-severe spasticity in the lower extremities received BTX for the first time in life into the thigh adductor, knee flexor and foot flexor muscle groups. Results were evaluated using Modified Ashworth's Scale, Visual (Analogue) Scale for Pain Assessment, Modified Rivermead Mobility Index and Repty Functional Index prior to and three weeks after the administration of the toxin. RESULTS: Improvement was observed in most patients, usually manifesting as reductions or resolution of pain. Mild side effects (low-grade fever and flu-like symptoms) occurred in only one patient. CONCLUSIONS: Our study confirmed the efficacy and safety of BTX for focal lower limb spasticity in adults. PMID- 17721427 TI - Physical activity of elderly patients after total hip arthroplasty. AB - BACKGROUND: Total hip arthroplasty (THA) is the most common method of treatment of severe hip osteoarthritis. There is little data concerning the physical activity of total hip arthroplasty patients in Poland and investigations to explore this area are useful. The aim of the study was to describe the post operative physical activity of total hip arthroplasty patients. MATERIAL AND METHODS: A total of 146 adult people were examined, among which 28 men and 41 women had undergone total hip arthroplasty due to primary osteoarthritis of the hip, while another 32 men and 41 women matched for age who had not undergone hip surgery for osteoarthritis served as controls. The physical activity of study participants was assessed with the 7-Day Physical Activity Recall Questionnaire. All participants were also asked about the type and amount of physical activity they engaged in to maintain good health. RESULTS AND CONCLUSIONS: Physical activity measured as the total amount of calories expended through physical activity per week was similar in the post-THA patients compared to the controls. The only differences were a smaller amount of calories expended during low intensity physical activity by men after total hip arthroplasty compared to men who had not undergone surgery for osteoarthritis and a smaller amount of calories expended through high-intensity physical activity by women after total hip arthroplasty compared to female controls. The kinds of recreational physical activity most commonly practised by patients a mean of two years after total hip arthroplasty were marching, bicycling and general body conditioning exercises (usually the continuation of exercises recommended during post-operative rehabilitation). The percentage of post-THA patients undertaking physical activity for the prevention of non-communicable diseases was low. Physical activity should be more effectively encouraged in patients after total hip arthroplasty. PMID- 17721428 TI - The correlation of selected physical examination findings and the efficacy of physiotherapy for chronic lumbosacral pain. AB - BACKGROUND: Lumbosacral pain is a significant social problem. Effective treatment of this ailment should be based on thorough diagnostic work-up. The goal of the present study was to determine which physical examination findings can help predict a positive outcome of physiotherapy, including kinesitherapy and physical therapy, aimed at symptomatic improvement. MATERIAL AND METHODS: The study group consisted of 50 patients with lumbosacral pain syndromes presenting as lumbalgia and ischialgia. RESULTS: Statistically significant correlations were ascertained between certain physical examination findings before the therapy and after the therapy. CONCLUSION: The crossed Lasegue sign was the only component of the physical examination that correlated with the dynamic efficacy of the rehabilitation treatment. PMID- 17721429 TI - Penetration of a selected antibiotic and antiseptic into a biofilm formed on orthopedic steel implants. AB - BACKGROUND: The aim of the study was to determine the impact of octenidine hydrochloride and gentamicin on bacterial survival and reduction of biofilms formed on orthopaedic metal implants. MATERIAL AND METHODS: We studied metal orthopaedic components (screws, nails, fragments of wires used in Ilizarov devices) and a bone sequester. The presence and intensity of biofilm formation on the medical biomaterials was determined using the method of Richards et al. by visual evaluation of 2,3,5-triphenyl tetrazolium chloride (TTC) reduction by viable bacteria. The presence and structure of the biofilm on the components of the Ilizarov device, screws and bone sequester was also studied by electron microscopy. Bacterial survival in the biofilm following exposure to the antibiotic and antiseptic was studied by CLSI microdilution method in microtitre plates using TTC. Results. Most of the 16 strains (S. aureus, S. epidermidis, E. coli, Enterobacter) isolated from orthopaedic implants were able to form a biofilm. Established biofilms were resistant to gentamicin and octenidine hydrochloride but demonstrated greater susceptibility to octenidine. CONCLUSIONS: The results of the study indicate that octenidine hydrochloride is more effective than gentamicin in the treatment of infections associated with the formation of a biofilm on orthopaedic implants. PMID- 17721430 TI - Tumours of the metatarsus. AB - BACKGROUND: Tumours of the metatarsus are rare and more frequently affect males. Relevant literature to date has mostly been confined to case reports. Single cases of the following tumours have been discussed: giant cell tumour, metastases (lung, prostate gland), chondroblastoma, aneurysmal bone cyst, Ewing's sarcoma, clear cell carcinoma, osteosarcoma, intraosseous ganglion, chondromyxoid fibroma and granuloma. We present our own clinical experience with metatarsal tumours during the period of the last 20 years. The aim of the present study was to carry out a systematic examination of metatarsal tumours with regard to methods of diagnosis (location) and morphology. MATERIAL AND METHODS: Fifteen patients with metatarsal tumours were diagnosed in the Department of Orthopaedics in Warsaw. Biplane radiographs were obtained as the initial examination in all cases. Subsequent work-up included angiography in three patients, ultrasonography in six and MRI in five patients. The results were histopathologically verified. RESULTS: Most of the metatarsal tumours were benign. Malignancies were found in four patients. CONCLUSIONS: 1. Bone tumours are rarely located in the metatarsus. 2. The presenting clinical and radiological signs of metatarsal tumours are usually not characteristic and may be difficult to detect. 3. The biplane X-ray should always be the first diagnostic test. Further diagnostic work-up (ultrasonography, CT, MRI) depends on the initial radiological findings. 4. The frequently unequivocal presentation of metatarsal tumours requires a multidisciplinary diagnosis involving a clinician, a radiologist and a histopathologist. PMID- 17721431 TI - Modelling breast cancer: one size does not fit all. AB - Breast cancer is not a single disease, but is instead a collection of diseases that have distinct histopathological features, genetic and genomic variability, and diverse prognostic outcomes. Thus, no individual model would be expected to completely recapitulate this complex disease. Here, the models commonly used to investigate breast cancer including cell lines, xenografts and genetically engineered mice, are discussed to help address the question: what is the most powerful way to investigate this heterogeneous disease? PMID- 17721432 TI - Role of JAK2 in the pathogenesis and therapy of myeloproliferative disorders. AB - The myeloproliferative disorders polycythaemia vera (PV), essential thombocythaemia (ET), and primary myelofibrosis (PMF) are clonal disorders of multipotent haematopoietic progenitors. The genetic cause of these diseases was not known until 2005, when several independent groups demonstrated that most patients with PV, ET and PMF acquire a single point mutation in the cytoplasmic tyrosine kinase JAK2 (JAK2V617F). These discoveries have changed the landscape for diagnosis and classification of PV, ET and PMF, and show the ability of genomic technologies to identify new molecular targets in human malignancies with pathogenetic, diagnostic and therapeutic significance. PMID- 17721433 TI - Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. AB - Epidemiological studies indicate that vitamin D insufficiency could have an aetiological role in various human cancers. Preclinical research indicates that the active metabolite of vitamin D, 1alpha,25(OH)2D3, also known as calcitriol, or vitamin D analogues might have potential as anticancer agents because their administration has antiproliferative effects, can activate apoptotic pathways and inhibit angiogenesis. In addition, 1alpha,25(OH)2D3 potentiates the anticancer effects of many cytotoxic and antiproliferative anticancer agents. Here, we outline the epidemiological, preclinical and clinical studies that support the development of 1alpha,25(OH)2D3 and vitamin D analogues as preventative and therapeutic anticancer agents. PMID- 17721434 TI - Building better magic bullets--improving unconjugated monoclonal antibody therapy for cancer. AB - The potential of monoclonal antibodies to effectively treat cancer is beginning to be widely acknowledged. Advances in antibody engineering make it possible to produce various recombinant proteins that exploit the specificity of the antibody combining site to manipulate tumour-related signalling, and to stimulate anti tumour immune responses. Future advances in the field will rely on the improved identification of functional antibody targets to perturb cancer-relevant signalling, and by the improved selection of tumours that can be effectively treated. These advances will be complemented by the use of antibodies that induce clinically meaningful host-protective immune responses. But, can we afford this progress? PMID- 17721435 TI - Oestrogen-receptor-mediated transcription and the influence of co-factors and chromatin state. AB - Oestrogen receptor-alpha (ERalpha)-regulated transcription in breast cancer cells involves protein co-factors that contribute to the regulation of chromatin structure. These include co-factors with the potential to regulate histone modifications such as acetylation or methylation, and therefore the transcriptional state of target genes. Although much of the information regarding the interaction of specific co-factors with ER has been generated by studying specific promoter regions, we now have an improved understanding of the nature of these interactions and are better placed to relate these with ER activity and potentially with the activity of breast cancer drugs, including tamoxifen. PMID- 17721436 TI - Acinus-provoked protein kinase C delta isoform activation is essential for apoptotic chromatin condensation. AB - Histone H2B phosphorylation tightly correlates with chromatin condensation during apoptosis. The caspase-cleaved acinus (apoptotic chromatin condensation inducer in the nucleus) provokes chromatin condensation in the nucleus, but the molecular mechanism accounting for this effect remains elusive. Here, we report that the active acinus p17 fragment initiates H2B phosphorylation and chromatin condensation by activating protein kinase C delta isoform (PKC-delta). We show that p17 binds to both Mst1 and PKC-delta, which is upregulated by apoptotic stimuli, enhancing their kinase activities. Acinus mutant susceptible to degradation elicits stronger chromatin condensation and higher H2B phosphorylation than wild-type acinus. Dominant-negative PKC-delta but not Mst1 robustly blocks acinus-initiated H2B phosphorylation. Surprisingly, depletion of Mst1 triggers caspase-3 activation, provoking H2B phosphorylation through activating PKC-delta. Further, acinus-elicited H2B phosphorylation and chromatin condensation are abrogated in PKC-delta-deficient mouse embryonic fibroblast cells and siRNA-knocked down PC12 cells. Thus, PKC-delta but not Mst1 acts as a physiological downstream kinase of acinus in promoting H2B phosphorylation and chromatin condensation. PMID- 17721437 TI - Reversible phosphorylation of Drp1 by cyclic AMP-dependent protein kinase and calcineurin regulates mitochondrial fission and cell death. AB - Opposing mitochondrial fission and fusion reactions determine the shape and interconnectivity of mitochondria. Dynamin-related protein 1 (Drp1) is an ancient mechanoenzyme that uses GTP hydrolysis to power the constriction and division of mitochondria. Although Drp1-mediated mitochondrial fragmentation is recognized as an early event in the apoptotic programme, acute regulation of Drp1 activity is poorly understood. Here, we identify a crucial phosphorylation site that is conserved in all metazoan Drp1 orthologues. Ser 656 is phosphorylated by cyclic AMP-dependent protein kinase and dephosphorylated by calcineurin, and its phosphorylation state is controlled by sympathetic tone, calcium levels and cell viability. Pseudophosphorylation of Drp1 by mutation of Ser 656 to aspartic acid leads to the elongation of mitochondria and confers resistance to various pro apoptotic insults. Conversely, the constitutively dephosphorylated Ser656Ala mutant Drp1 promotes mitochondrial fragmentation and increases cell vulnerability. Thus, Drp1 phosphorylation at Ser 656 provides a mechanism for the integration of cAMP and calcium signals in the control of mitochondrial shape, apoptosis and other aspects of mitochondrial function. PMID- 17721438 TI - BS69 is involved in cellular senescence through the p53-p21Cip1 pathway. AB - The multidomain-containing cellular protein BS69 interacts with adenovirus E1A and several other viral and cellular factors, and acts as a transcription repressor. Here, we show that BS69 is involved in the p53-p21Cip1-mediated senescence pathway. Knockdown of BS69 by RNA interference in human primary fibroblasts results in elevated levels of p21Cip1 and the appearance of several senescent markers, including enhanced senescence-associated beta-galactosidase activity and formation of senescence-associated heterochromatin foci. Importantly, knockdown of either p53 or p21Cip1, but not p16(INK4a) or Rb, allows cells to bypass premature senescence that is induced by BS69 knockdown. Furthermore, we show that BS69 forms complexes with both p53 and p400, and that BS69 associates with the p21Cip1 promoter through p53. Together, our data indicate that BS69 is involved in cellular senescence mainly through the p53 p21Cip1 pathway. PMID- 17721439 TI - Structural insights into the recognition of substrates and activators by the OSR1 kinase. AB - The oxidative-stress-responsive kinase 1 (OSR1) and the STE20/SPS1-related proline/alanine-rich kinase (SPAK) are key enzymes in a signalling cascade regulating the activity of Na(+)/K(+)/2Cl(-) co-transporters (NKCCs) in response to osmotic stress. Both kinases have a conserved carboxy-terminal (CCT) domain, which recognizes a unique peptide (Arg-Phe-Xaa-Val) motif present in OSR1- and SPAK-activating kinases (with-no-lysine kinase 1 (WNK1) and WNK4) as well as its substrates (NKCC1 and NKCC2). Here, we describe the structural basis of this recognition event as shown by the crystal structure of the CCT domain of OSR1 in complex with a peptide containing this motif, derived from WNK4. The CCT domain forms a novel protein fold that interacts with the Arg-Phe-Xaa-Val motif through a surface-exposed groove. An intricate web of interactions is observed between the CCT domain and an Arg-Phe-Xaa-Val motif-containing peptide derived from WNK4. Mutational analysis shows that these interactions are required for the CCT domain to bind to WNK1 and NKCC1. The CCT domain structure also shows how phosphorylation of a Ser/Thr residue preceding the Arg-Phe-Xaa-Val motif results in a steric clash, promoting its dissociation from the CCT domain. These results provide the first molecular insight into the mechanism by which the SPAK and OSR1 kinases specifically recognize their upstream activators and downstream substrates. PMID- 17721440 TI - Substrate binding to histone deacetylases as shown by the crystal structure of the HDAC8-substrate complex. AB - Histone deacetylases (HDACs)-an enzyme family that deacetylates histones and non histone proteins-are implicated in human diseases such as cancer, and the first generation of HDAC inhibitors are now in clinical trials. Here, we report the 2.0 A resolution crystal structure of a catalytically inactive HDAC8 active-site mutant, Tyr306Phe, bound to an acetylated peptidic substrate. The structure clarifies the role of active-site residues in the deacetylation reaction and substrate recognition. Notably, the structure shows the unexpected role of a conserved residue at the active-site rim, Asp 101, in positioning the substrate by directly interacting with the peptidic backbone and imposing a constrained cis conformation. A similar interaction is observed in a new hydroxamate inhibitor HDAC8 structure that we also solved. The crucial role of Asp 101 in substrate and inhibitor recognition was confirmed by activity and binding assays of wild-type HDAC8 and Asp101Ala, Tyr306Phe and Asp101Ala/Tyr306Phe mutants. PMID- 17721441 TI - New androgen receptor genomic targets show an interaction with the ETS1 transcription factor. AB - The androgen receptor (AR) initiates important developmental and oncogenic transcriptional pathways. The AR is known to bind as a homodimer to 15-base pair bipartite palindromic androgen-response elements; however, few direct AR gene targets are known. To identify AR promoter targets, we used chromatin immunoprecipitation with on-chip detection of genomic fragments. We identified 1,532 potential AR-binding sites, including previously known AR gene targets. Many of the new AR target genes show altered expression in prostate cancer. Analysis of sequences underlying AR-binding sites showed that more than 50% of AR binding sites did not contain the established 15 bp AR-binding element. Unbiased sequence analysis showed 6-bp motifs, which were significantly enriched and were bound directly by the AR in vitro. Binding sequences for the avian erythroblastosis virus E26 homologue (ETS) transcription factor family were also highly enriched, and we uncovered an interaction between the AR and ETS1 at a subset of AR promoter targets. PMID- 17721442 TI - Paf1 complex homologues are required for Notch-regulated transcription during somite segmentation. AB - Members of the yeast polymerase-associated factor 1 (Paf1) complex, which is composed of at least five components (Paf1, Rtf1, Cdc73, Leo1 and Ctr9), are conserved from yeast to humans. Although these proteins have been implicated in RNA polymerase II-mediated transcription, their roles in vertebrate development have not been explained. Here, we show that a zebrafish mutant with a somite segmentation defect is deficient in rtf1. In addition, embryos deficient in rtf1 or ctr9 show abnormal development of the heart, ears and neural crest cells. rtf1 is required for correct RNA levels of the Notch-regulated genes her1, her7 and deltaC, and also for Notch-induced her1 expression in the presomitic mesoderm. Furthermore, the phenotype observed in rtf1-deficient mutants is enhanced by an additional deficiency in mind bomb, which encodes an effector of Notch signalling. Therefore, zebrafish homologues of the yeast Paf1 complex seem to preferentially affect a subset of genes, including Notch-regulated genes, during embryogenesis. PMID- 17721443 TI - Messenger RNA conformations in the ribosomal E site revealed by X-ray crystallography. AB - A comparison of messenger RNA in X-ray crystal structures of 70S ribosomal complexes in the initiation, post-initiation and elongation states of translation shows distinct conformational differences in the exit (E) codon. Here, we present structural evidence indicating that, after the initiation event, the E codon nucleotides relax and form a classical A-helical conformation. This conformation is similar to that of the P and A codons, and is favourable for establishing Watson-Crick interactions with the anticodon of E-site transfer RNA. PMID- 17721444 TI - The Arabidopsis TOR kinase links plant growth, yield, stress resistance and mRNA translation. AB - Plants, unlike animals, have plastic organ growth that is largely dependent on environmental information. However, so far, little is known about how this information is perceived and transduced into coherent growth and developmental decisions. Here, we report that the growth of Arabidopsis is positively correlated with the level of expression of the TARGET OF RAPAMYCIN (TOR) kinase. Diminished or augmented expression of the AtTOR gene results in a dose-dependent decrease or increase, respectively, in organ and cell size, seed production and resistance to osmotic stress. Strong downregulation of AtTOR expression by inducible RNA interference also leads to a post-germinative halt in growth and development, which phenocopies the action of the plant hormone abscisic acid, to an early senescence and to a reduction in the amount of translated messenger RNA. Thus, we propose that the AtTOR kinase is one of the contributors to the link between environmental cues and growth processes in plants. PMID- 17721445 TI - A multiplicity of cell death pathways. Symposium on apoptotic and non-apoptotic cell death pathways. PMID- 17721447 TI - Memories of Santa Fe. Symposium on immunologic memory. PMID- 17721446 TI - Rad9 BRCT domain interaction with phosphorylated H2AX regulates the G1 checkpoint in budding yeast. AB - Phosphorylation of histone H2A or H2AX is an early and sensitive marker of DNA damage in eukaryotic cells, although mutation of the conserved damage-dependent phosphorylation site is well tolerated. Here, we show that H2A phosphorylation is required for cell-cycle arrest in response to DNA damage at the G1/S transition in budding yeast. Furthermore, we show that the tandem BRCT domain of Rad9 interacts directly with phosphorylated H2A in vitro and that a rad9 point mutation that abolishes this interaction results in in vivo phenotypes that are similar to those caused by an H2A phosphorylation site mutation. Remarkably, similar checkpoint defects are also caused by a Rad9 Tudor domain mutation that impairs Rad9 chromatin association already in undamaged cells. These findings indicate that constitutive Tudor domain-mediated and damage-specific BRCT domain phospho-H2A-dependent interactions of Rad9 with chromatin cooperate to establish G1 checkpoint arrest. PMID- 17721448 TI - Expanding horizons at Big Sky. Symposium on ubiquitin and signaling. PMID- 17721449 TI - EB120.R5--so what? PMID- 17721450 TI - Larvae in the mouth. PMID- 17721451 TI - Free way space. PMID- 17721452 TI - Outdated definition. PMID- 17721453 TI - No causal link. PMID- 17721454 TI - Virtually impossible. PMID- 17721455 TI - Treating the cause. PMID- 17721461 TI - Collective awarded cash for HIV research. PMID- 17721472 TI - Teaching posterior composite resin restorations in the United Kingdom and Ireland: consensus views of teachers. AB - Posterior composite resin restorations are an established feature of contemporary dental practice and all new dental graduates should be competent in providing such treatments for their patients. Surveys of educational curricula in this area in the United Kingdom and Ireland, as well as North America, have demonstrated variations both within and between dental schools. Such inconsistency does not help new dental school graduates, and may lead to confusion. At the British Association of Teachers of Conservative Dentistry Annual Conference held in Birmingham in September 2005, a session was devoted to the development of guidelines for dental schools on teaching posterior composite resin restorations to dental undergraduates. The theme of the conference concerned the teaching implications for changing from amalgam to composite. Two of the principal speakers at the meeting (Joost Roeters and Niek Opdam) were from the dental school at the University of Nijmegen in the Netherlands. This school was the first in Europe to discontinue the use of dental amalgam in its undergraduate curriculum over a decade ago. This paper reports the consensus views of those present on guidelines for teaching posterior composite resin restorations to dental undergraduate students. PMID- 17721473 TI - Restoration of periodontally compromised dentitions using cross-arch bridges. Principles of perio-prosthetic patient management. AB - Severe periodontal disease often leads to tooth loss, necessitating prosthetic rehabilitation to restore function and aesthetics. The concept of perio prosthetic treatment using extensive bridges of cross-arch design was introduced approximately 30 years ago. Long term follow-up studies have shown that teeth with reduced periodontal support can be used as abutments for extensive fixed prostheses, provided periodontal disease has been treated successfully, and an effective recall programme has been instituted to prevent periodontal disease recurrence. Low complication rates have been reported with these extensive constructions. PMID- 17721480 TI - Familial human hypodontia--is it all in the genes? AB - The congenital absence of teeth is one of the commonest developmental abnormalities seen in human populations. Familial hypodontia or oligodontia represents an absence of varying numbers of primary and/or secondary teeth as an isolated trait. While much progress has been made in understanding the developmental basis of tooth formation, knowledge of the aetiological basis of inherited tooth loss remains poor. The study of mouse genetics has uncovered a large number of candidate genes for this condition, but mutations in only three have been identified in human pedigrees with familial hypodontia or oligodontia: MSX1, PAX9 and AXIN2. This suggests that these conditions may represent a more complex multifactorial trait, influenced by a combination of gene function, environmental interaction and developmental timing. Completion of the human genome project has made available the DNA sequence of the collected human chromosomes, allowing the localisation of all human genes and, ultimately, determination of their function. Therefore it is likely that our understanding of this complex developmental process will continue to improve, not only during normal development but also when things go wrong. PMID- 17721481 TI - Mandibular etymologies. AB - Many of us can remember how much our vocabulary grew as undergraduates and indeed has continued to grow as dental professionals. For many of us not trained in Latin and Greek we have often been too busy learning what the word means to understand why it means what it does. This article aims to clarify things a little. It explains where words relating to the mandible come from, why we use them now and also shows how they are related to other similar words in everyday use. PMID- 17721494 TI - The BDA Dental Academic Staff Group Student Elective Workshop. AB - In the current climate in dental education, many schools are re-evaluating the role of the student elective in the curriculum, with two schools no longer running elective programmes. In order to discuss the future of student electives in the dental curriculum, the Dental Academic Staff Group (DASG) of the British Dental Association organised a Student Elective Workshop, which attracted 42 delegates including nine student representatives. The following article is an account of the Workshop and its conclusions. PMID- 17721497 TI - Cost-effectiveness of latanoprost and timolol maleate for the treatment of glaucoma in Scandinavia and the United Kingdom, using a decision-analytic health economic model. AB - PURPOSE: To assess the cost-effectiveness of latanoprost or timolol in glaucoma treatment in Norway, Sweden, Denmark (Scandinavia) and the United Kingdom (UK). METHODS: A Markov model was constructed to perform a cost-effectiveness analysis. Health states were 'stable' and 'progressed' glaucoma, and transition probabilities for both primary open-angle and exfoliation glaucoma were derived from the medical literature. Practice patterns were obtained from surveys completed by 54 ophthalmologists geographically dispersed throughout each country. Country specific unit costs were used for medications, patient visits, diagnostics, and therapeutic procedures. RESULTS: Over the life of the model latanoprost was less expensive than timolol by 5.3-7.6% (Scandinavia) and 2.1% (UK). Following adjustments, therapy in the original timolol-treated cohort was slightly more effective in each country with a difference in 0.003-0.015 years to progression of glaucoma existing between latanoprost. This may have resulted from the model design, which reflected that physicians ultimately control most patients' glaucoma over 5 years by adding or changing therapy. The associated incremental cost-effectiveness ratios for latanoprost vs timolol generated by the Scandinavian and the UK models, respectively, were: Norway 351,396 NOK; Sweden 988,985 SEK; Denmark 351,641; and the UK 4751 GBP. CONCLUSIONS: Over 5 years, in the UK timolol is the cost-effective option, whereas in Scandinavia latanoprost may be the cost-effective alternative to timolol. PMID- 17721499 TI - Peripapillary intrachoroidal cavitation in high myopia: reappraisal. AB - PURPOSE: To evaluate optical coherence tomography (OCT) and clinical findings of a peripapillary lesion in high myopia recently named peripapillary detachment in pathologic myopia (PDPM) or intrachoroidal cavitation. METHODS: Observational case report by chart review, analysis of colour fundus photography, fluorescein angiography, and OCT in 16 eyes of 12 patients with myopic degeneration and the presence of a slightly elevated, patchy peripapillary, yellow-orange lesion on the fundus. RESULTS: Patients were mean age 53.1+/-10.7 years, with a spherical equivalent refractive error of -10.99+/-3.33 D and mean axial length of 27.34+/ 1.44 mm. The mean best-corrected visual acuity was log MAR 0.3+/-0.2 (between 20/100 and 20/20). Six eyes also showed myopic maculopathy. In 13 eyes, OCT showed an intrachoroidal hyporeflective space located below the normal plane of the retinal pigment epithelium. Six of these 13 eyes were found to have apparent communication between the intrachoroidal cavity and the vitreous space at the junction of the lesion and the myopic conus. In three eyes, OCT revealed intrachoroidal splitting. The fluorescein angiogram showed early hypofluorescence, without pooling or staining in late phase. CONCLUSIONS: The yellow-orange elevated patchy lesions adjacent to the peripapillary conus in high myopic eyes may represent either intrachoroidal cavitation or choroidal schisis, which may be different stages of one disease spectrum. Vitreous fluid may be the source of the disruption of choroid and fluid accumulation. PMID- 17721498 TI - Cytotoxicity of silicone oil on cultivated human corneal endothelium. AB - BACKGROUND AND OBJECTIVE: To investigate the cytotoxic effects of silicone oil on the cultivated human corneal endothelial cells (CEs). METHODS: We cultured human CE and passed them in insert wells that allowed the apical side of CE monolayer in contact with the silicone oil. The tested silicone oils were of two different viscosities, 1,000 and 5,000 centistoke (CS). MTS proliferation bioassay and calcein-acetoxymethyl ester (CAM)-ethidium homodimer staining were performed to evaluate cell viability after CEs were co-cultured with silicone oils for 48 h. Apoptosis of CEs was evaluated by TdT-mediated dUTP nick-end labelling (TUNEL) stain. RESULTS: The MTS bioassay showed that contact of silicone oil inhibited CE proliferation. The higher viscosity (5,000 CS) silicone oil suppressed cell cycling significantly more than the lower viscosity (1,000 CS) silicone oil. CAM ethidium homodimer staining revealed CE death, 9.1+/-0.1% (1,000 CS silicone oil) and 41.6+/-0.4% (5,000 CS), but apoptosis played only minor role in silicone oil toxicity, 1.7+/-0.1% (1,000 CS silicone oil) and 9.4+/-0.1% (5,000 CS). CONCLUSIONS: Silicone oil is cytotoxic to cultivated human CEs. Avoiding the forward migration of silicone oil to the anterior chamber and corneal CE contact is critical in preventing silicone oil-associated keratopathy. Silicone oil should be removed as early as possible once the goal of tamponade has been achieved. PMID- 17721500 TI - An unusual ocular manifestation in fanconi anaemia: anterior ischaemic syndrome. PMID- 17721501 TI - Bilateral autoimmune optic neuritis and vitreitis related to CRMP-5-IgG: intravitreal triamcinolone acetonide therapy of four eyes. AB - PURPOSE: To report the vision outcome following intravitreal triamcinolone acetonide (IVTA) as adjunctive therapy in four eyes of two patients with paraneoplastic autoimmune optic neuritis and vitreitis related to CRMP (Collapsin Response-Mediator Protein)-5-IgG. DESIGN: Retrospective case series.MethodsChart review of four eyes. RESULTS: Preoperative visions were: patient 1, 20/50 OD, 20/25 OS; patient 2, counting fingers (CF) at two feet OD, and CF at three feet OS. At last follow-up, the postoperative visions were 20/40, 20/50 and 20/200, 20/60, respectively. All signs of optic disc swelling and vitreitis had abated. CONCLUSIONS: Use of IVTAin paraneoplastic autoimmune optic neuritis and vitreitis related to CRMP-5-IgG was followed by a marked decrease in inflammation and stabilization or improvement of vision. These observations support this form of adjunctive therapy in patients whose intraocular pathology is attributed to paraneoplastic autoimmunity. PMID- 17721502 TI - Argon laser photocoagulation for the treatment of polypoidal choroidal vasculopathy. AB - AIM: To evaluate the efficacy of conventional argon laser for the treatment of serosanguineous maculopathy secondary to polypoidal choroidal vasculopathy (PCV). METHODS: A retrospective audit of patients who had argon laser photocoagulation to angiographically determined polypoidal lesions and subsequently followed up at 1, 3, 6, and 12 months post treatment. RESULTS: Twenty-one eyes (75%) had stable or improved vision at 12 months. Twenty-three eyes had extrafoveal, two eyes had juxtafoveal, and three eyes had subfoveal polyps. In the extrafoveal group, 18 eyes (78%) had stable or improved vision at 12 months. Eighteen eyes (64.3%) showed clinical or angiographic resolution of maculopathy. Three eyes (10.7%) had recurrence of polyps subfoveally, three eyes (10.7%) had subsequent choroidal neovascularisation, and four eyes (14.3%) had persistent leakage with neurosensory detachment. CONCLUSION: In our study, 18 of the 23 eyes which had extrafoveal polyps had stable or improved best-corrected visual acuity and showed complete resolution of maculopathy at 12 months follow-up. Argon laser photocoagulation would appear to be most beneficial for extrafoveal PCV. However, in view of the retrospective nature of this study, the true efficacy of argon laser treatment would have to be evaluated with a larger, prospective and randomised controlled trial. PMID- 17721503 TI - Benchmark standards for refractive outcomes after NHS cataract surgery. AB - PURPOSE: To establish benchmark standards for refractive outcome after cataract surgery in the National Health Service when implementing the 2004 biometry guidelines of the Royal College of Ophthalmologists and customising A constants. METHODS: Three cycles of prospective data were collected throughout the cataract care pathway on all patients using an electronic medical record system (Medisoft Ophthalmology), between January 2003 and February 2006. The electronic medical record automatically recommends the formula to be used according to the College guidelines and allows A constants to be customised separately for either ultrasound or partial coherence interferometry methods of axial length measurement and for different intraocular lens models. Consultants and trainees performed routine phacoemulsification cataract surgery and new intraocular lens models were introduced during the cycles. Uncomplicated cases with 'in-the-bag fixation', achieving 6/12 Snellen acuity or better were included. Community ophthalmic opticians performed refraction at 4 weeks. RESULTS: The postoperative subjective refraction was within 1 D of the predicted value in 79.7% of the 952 cases in cycle 1, 83.4% of 2406 cases in cycle 2, and 87.0% of 1448 cases in cycle 3. CONCLUSIONS: On the basis of our data, using College formula, optimising A constants and partial coherence interferometry, a benchmark standard of 85% of patients achieving a final spherical equivalent within 1 D of the predicted figure and 55% of patients within 0.5 D should be adopted. PMID- 17721504 TI - Retinal nerve fibre layer imaging compared with histological measurements in a human eye. AB - PURPOSE: A feasibility study comparing retinal nerve fibre layer (RNFL) thickness values obtained with imaging devices against RNFL thickness measurements obtained histologically in a human eye. DESIGN: A single patient scheduled for orbital exenteration, who still possessed a healthy functioning eye. METHODS: Before surgery, the eye was imaged using optical coherence tomography (OCT) and scanning laser polarimetry (SLP). After orbital exenteration, the globe was sectioned, and 100 equidistant RNFL thickness measurements were obtained for each of four concentric rings centred on the optic disc, with diameters of 3.0, 3.5, 4.0, and 4.5 mm. RESULTS: RNFL thickness was found to be inversely related to the distance from the centre of the optic disc along each radial meridian. Peripapillary RNFL thickness was found comparable for histology, OCT, and SLP. RNFL thickness measured histologically confirmed a 'double hump' pattern, peaking at the superior and inferior poles. Histologically derived RNFL thickness (microm), at 3.0 and 3.5 mm diameter ring ranged between 30-135 and 25-115 respectively. In comparison, the 3.0 mm diameter GDx data ranged between 25 and 100, and the 3.4 mm diameter OCT data between 40 and 175. CONCLUSIONS: Imaging data appear qualitatively similar when compared to the histologically derived data. Quantitative differences may be partly due to scaling differences and histological artefacts. The histological analysis approach demonstrated in this study can potentially serve to validate imaging-derived data, as well as help improve our understanding of RNFL loss in glaucoma. PMID- 17721505 TI - Screening for ocular surface disease in the intensive care unit. AB - PURPOSE: Ventilated patients in the intensive care unit (ICU) often develop exposure keratopathy. This predisposes to the development of bacterial keratitis, which in ICU is often bilateral, with a high risk of perforation. As regular examinations of all ventilated patients by ophthalmologists would be impractical, the purpose of this study was to assess whether ICU staff can screen reliably for keratopathy. METHODS: A prospective study was performed in a general adult ICU. Twice each week, two junior ICU doctors examined the lid position and ocular surface of all patients who had been continuously sedated for more than 24 h, using fluorescein and a pen torch with a blue filter. An ophthalmologist performed similar examinations using a portable slit lamp. RESULTS: A total of 48 ocular examinations were performed in 18 patients. Exposure keratopathy was found by the ophthalmologist in 37.5% of examinations and by ICU doctors in 31.3% of examinations. ICU doctors had a sensitivity of 77.8% and a specificity of 96.7% in detecting keratopathy, when compared with the findings of the ophthalmologist. All cases missed by ICU doctors had punctate erosions of less than 5% of the corneal surface. Keratopathy was significantly commoner in patients with incomplete lid closure than in patients with closed lids (70.0 vs 28.9%; two tailed Fisher's exact test P=0.027). CONCLUSIONS: ICU staff can perform screening examinations for exposure keratopathy with reasonable sensitivity and specificity. Regular screening by ICU staff would facilitate appropriate treatment of exposure keratopathy and promote earlier identification of cases of keratitis. PMID- 17721506 TI - Long-term results of balloon dacryocystoplasty: success rates according to the site and severity of the obstruction. AB - PURPOSE: To evaluate the long-term patency of lacrimal drainage system (LDS) after balloon dacryocystoplasty (BD) and to give the long-term success rates according to the severity and localization of the obstruction. METHODS: Between May 1993 and December 2003, BD was attempted in 117 eyes of 108 patients with idiopathic-acquired LDS obstruction. Patients with active dacryocystitis, dacryolithiasis, traumatic obstruction or lacrimal mass, obstructions at the superior or inferior canaliculi lateral to the common canaliculus, and follow-up period less than 36 months were excluded from the study. RESULTS: The results of BD were evaluated in 99 eyes of 94 cases. The obstruction was seen at the common canaliculus in seven eyes, proximal nasolacrimal duct in 70 eyes, and distal nasolacrimal duct in 22 eyes. The mean follow-up period was 100.0+/-38.4 months (range: 36-142 months). The long-term overall success rate was 40.8% (20/49 eyes) in complete obstruction and 68% (34/50 eyes) in partial obstruction. The clinical success rate was 57.1% in common canalicular (complete: 33.3%, partial: 75%), 50% in proximal nasolacrimal duct (complete: 38.5%, partial: 64.5%), and 68.2% in distal nasolacrimal duct (complete: 57.1%, partial: 73.3%) obstructions. The overall success was 54.5% (54/99 eyes) for the entire series at the last clinical follow-up visit. CONCLUSION: The long-tem success rate of BD for the treatment of epiphora is low and is not comparable to conventional dacryocystorhinostomy. More predictable results can only be achieved in carefully selected patients and this procedure can be recommended in cases demonstrating partial obstruction of the distal nasolacrimal duct. PMID- 17721508 TI - Structural basis of Dscam isoform specificity. AB - The Dscam gene gives rise to thousands of diverse cell surface receptors thought to provide homophilic and heterophilic recognition specificity for neuronal wiring and immune responses. Mutually exclusive splicing allows for the generation of sequence variability in three immunoglobulin ecto-domains, D2, D3 and D7. We report X-ray structures of the amino-terminal four immunoglobulin domains (D1-D4) of two distinct Dscam isoforms. The structures reveal a horseshoe configuration, with variable residues of D2 and D3 constituting two independent surface epitopes on either side of the receptor. Both isoforms engage in homo dimerization coupling variable domain D2 with D2, and D3 with D3. These interactions involve symmetric, antiparallel pairing of identical peptide segments from epitope I that are unique to each isoform. Structure-guided mutagenesis and swapping of peptide segments confirm that epitope I, but not epitope II, confers homophilic binding specificity of full-length Dscam receptors. Phylogenetic analysis shows strong selection of matching peptide sequences only for epitope I. We propose that peptide complementarity of variable residues in epitope I of Dscam is essential for homophilic binding specificity. PMID- 17721509 TI - Differential Notch signalling distinguishes neural stem cells from intermediate progenitors. AB - During brain development, neurons and glia are generated from a germinal zone containing both neural stem cells (NSCs) and more limited intermediate neural progenitors (INPs). The signalling events that distinguish between these two proliferative neural cell types remain poorly understood. The Notch signalling pathway is known to maintain NSC character and to inhibit neurogenesis, although little is known about the role of Notch signalling in INPs. Here we show that both NSCs and INPs respond to Notch receptor activation, but that NSCs signal through the canonical Notch effector C-promoter binding factor 1 (CBF1), whereas INPs have attenuated CBF1 signalling. Furthermore, whereas knockdown of CBF1 promotes the conversion of NSCs to INPs, activation of CBF1 is insufficient to convert INPs back to NSCs. Using both transgenic and transient in vivo reporter assays we show that NSCs and INPs coexist in the telencephalic ventricular zone and that they can be prospectively separated on the basis of CBF1 activity. Furthermore, using in vivo transplantation we show that whereas NSCs generate neurons, astrocytes and oligodendrocytes at similar frequencies, INPs are predominantly neurogenic. Together with previous work on haematopoietic stem cells, this study suggests that the use or blockade of the CBF1 cascade downstream of Notch is a general feature distinguishing stem cells from more limited progenitors in a variety of tissues. PMID- 17721510 TI - A diverse family of thermostable cytochrome P450s created by recombination of stabilizing fragments. AB - Thermostable enzymes combine catalytic specificity with the toughness required to withstand industrial reaction conditions. Stabilized enzymes also provide robust starting points for evolutionary improvement of other protein properties. We recently created a library of at least 2,300 new active chimeras of the biotechnologically important cytochrome P450 enzymes. Here we show that a chimera's thermostability can be predicted from the additive contributions of its sequence fragments. Based on these predictions, we constructed a family of 44 novel thermostable P450s with half-lives of inactivation at 57 degrees C up to 108 times that of the most stable parent. Although they differ by as many as 99 amino acids from any known P450, the stable sequences are catalytically active. Among the novel functions they exhibit is the ability to produce drug metabolites. This chimeric P450 family provides a unique ensemble for biotechnological applications and for studying sequence-stability-function relationships. PMID- 17721507 TI - The grapevine genome sequence suggests ancestral hexaploidization in major angiosperm phyla. AB - The analysis of the first plant genomes provided unexpected evidence for genome duplication events in species that had previously been considered as true diploids on the basis of their genetics. These polyploidization events may have had important consequences in plant evolution, in particular for species radiation and adaptation and for the modulation of functional capacities. Here we report a high-quality draft of the genome sequence of grapevine (Vitis vinifera) obtained from a highly homozygous genotype. The draft sequence of the grapevine genome is the fourth one produced so far for flowering plants, the second for a woody species and the first for a fruit crop (cultivated for both fruit and beverage). Grapevine was selected because of its important place in the cultural heritage of humanity beginning during the Neolithic period. Several large expansions of gene families with roles in aromatic features are observed. The grapevine genome has not undergone recent genome duplication, thus enabling the discovery of ancestral traits and features of the genetic organization of flowering plants. This analysis reveals the contribution of three ancestral genomes to the grapevine haploid content. This ancestral arrangement is common to many dicotyledonous plants but is absent from the genome of rice, which is a monocotyledon. Furthermore, we explain the chronology of previously described whole-genome duplication events in the evolution of flowering plants. PMID- 17721511 TI - Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors. AB - We describe a chemical proteomics approach to profile the interaction of small molecules with hundreds of endogenously expressed protein kinases and purine binding proteins. This subproteome is captured by immobilized nonselective kinase inhibitors (kinobeads), and the bound proteins are quantified in parallel by mass spectrometry using isobaric tags for relative and absolute quantification (iTRAQ). By measuring the competition with the affinity matrix, we assess the binding of drugs to their targets in cell lysates and in cells. By mapping drug induced changes in the phosphorylation state of the captured proteome, we also analyze signaling pathways downstream of target kinases. Quantitative profiling of the drugs imatinib (Gleevec), dasatinib (Sprycel) and bosutinib in K562 cells confirms known targets including ABL and SRC family kinases and identifies the receptor tyrosine kinase DDR1 and the oxidoreductase NQO2 as novel targets of imatinib. The data suggest that our approach is a valuable tool for drug discovery. PMID- 17721512 TI - Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. AB - Cardiomyocytes derived from human embryonic stem (hES) cells potentially offer large numbers of cells to facilitate repair of the infarcted heart. However, this approach has been limited by inefficient differentiation of hES cells into cardiomyocytes, insufficient purity of cardiomyocyte preparations and poor survival of hES cell-derived myocytes after transplantation. Seeking to overcome these challenges, we generated highly purified human cardiomyocytes using a readily scalable system for directed differentiation that relies on activin A and BMP4. We then identified a cocktail of pro-survival factors that limits cardiomyocyte death after transplantation. These techniques enabled consistent formation of myocardial grafts in the infarcted rat heart. The engrafted human myocardium attenuated ventricular dilation and preserved regional and global contractile function after myocardial infarction compared with controls receiving noncardiac hES cell derivatives or vehicle. The ability of hES cell-derived cardiomyocytes to partially remuscularize myocardial infarcts and attenuate heart failure encourages their study under conditions that closely match human disease. PMID- 17721513 TI - The lipid droplet is an important organelle for hepatitis C virus production. AB - The lipid droplet (LD) is an organelle that is used for the storage of neutral lipids. It dynamically moves through the cytoplasm, interacting with other organelles, including the endoplasmic reticulum (ER). These interactions are thought to facilitate the transport of lipids and proteins to other organelles. The hepatitis C virus (HCV) is a causative agent of chronic liver diseases. HCV capsid protein (Core) associates with the LD, envelope proteins E1 and E2 reside in the ER lumen, and the viral replicase is assumed to localize on ER-derived membranes. How and where HCV particles are assembled, however, is poorly understood. Here, we show that the LD is involved in the production of infectious virus particles. We demonstrate that Core recruits nonstructural (NS) proteins and replication complexes to LD-associated membranes, and that this recruitment is critical for producing infectious viruses. Furthermore, virus particles were observed in close proximity to LDs, indicating that some steps of virus assembly take place around LDs. This study reveals a novel function of LDs in the assembly of infectious HCV and provides a new perspective on how viruses usurp cellular functions. PMID- 17721514 TI - Correlated three-dimensional light and electron microscopy reveals transformation of mitochondria during apoptosis. AB - In addition to their role in cellular bioenergetics, mitochondria also initiate common forms of programmed cell death (apoptosis) through the release of proteins such as cytochrome c from the intermembrane and intracristal spaces. The release of these proteins is studied in populations of cells by western blotting mitochondrial and cytoplasmic fractions of cellular extracts, and in single cells by fluorescence microscopy using fluorescent indicators and fusion proteins. However, studying the changes in ultrastructure associated with release of proteins requires the higher resolution provided by transmission electron microscopy. Here, we have used fluorescence microscopy to characterize the state of apoptosis in HeLa cells treated with etoposide followed by electron microscopy and three-dimensional electron microscope tomography of the identical cells to study the sequence of structural changes. We have identified a remodelling of the inner mitochondrial membrane into many separate vesicular matrix compartments that accompanies release of proteins; however, this remodelling is not required for efficient release of cytochrome c. Swelling occurs only late in apoptosis after release of cytochrome c and loss of the mitochondrial membrane potential. PMID- 17721515 TI - Focal adhesion kinase controls actin assembly via a FERM-mediated interaction with the Arp2/3 complex. AB - Networks of actin filaments, controlled by the Arp2/3 complex, drive membrane protrusion during cell migration. How integrins signal to the Arp2/3 complex is not well understood. Here, we show that focal adhesion kinase (FAK) and the Arp2/3 complex associate and colocalize at transient structures formed early after adhesion. Nascent lamellipodia, which originate at these structures, do not form in FAK-deficient cells, or in cells in which FAK mutants cannot be autophosphorylated after integrin engagement. The FERM domain of FAK binds directly to Arp3 and can enhance Arp2/3-dependent actin polymerization. Critically, Arp2/3 is not bound when FAK is phosphorylated on Tyr 397. Interfering peptides and FERM-domain point mutants show that FAK binding to Arp2/3 controls protrusive lamellipodia formation and cell spreading. This establishes a new function for the FAK FERM domain in forming a phosphorylation regulated complex with Arp2/3, linking integrin signalling directly with the actin polymerization machinery. PMID- 17721516 TI - OL-Protocadherin is essential for growth of striatal axons and thalamocortical projections. AB - The ventral telencephalon in the embryonic brain is thought to provide guidance cues for navigation of thalamocortical axons, but the mechanisms involved remain largely elusive. OL-protocadherin (OL-pc), a member of the cadherin superfamily, is highly expressed by striatal neurons in the developing ventral telencephalon. Here we show that OL-pc-deficient (Pcdh10(-/-)) mice have defects in axon pathways through the ventral telencephalon; for example, thalamocortical and corticothalamic projections cannot cross the ventral telencephalon. In the ventral telencephalon, striatal axons fail to grow out, and, concomitantly, the caudal portion of the globus pallidus and the associated 'corridor' thought to be important for thalamocortical fiber navigation do not form. The inability of the striatum to extend axons is also observed in vitro. These results show that OL-pc is essential for both elongation of striatal axons and patterning of the putative guidance cues for thalamocortical projections. PMID- 17721522 TI - Noncompliance, documentation and FOIA: violators beware! PMID- 17721523 TI - Noncompliance, documentation and FOIA. PMID- 17721525 TI - Noncompliance, documentation and FOIA: VMO has the authority. PMID- 17721526 TI - Noncompliance, documentation and FOIA: out of luck, but what if? PMID- 17721527 TI - Skin nodules on multimammate mice (Mastomys coucha). PMID- 17721529 TI - Blood sample collection in lizards. AB - Blood sample collection in lizards is an important technique. This column describes techniques for sample collection from the ventral coccygeal vein and the ventral abdominal vein. PMID- 17721530 TI - Multimodality Chamber for coregistered anatomical and molecular imaging of small animals. AB - Modern imaging methods are applied extensively in translational animal research, and combined analysis of anatomical and functional imaging results is of increasing importance. Many imaging centers handle multiple independent animal colonies and use several imaging modalities, often in combination. The authors have developed and successfully tested a two-piece acrylic Multimodality Chamber that enables investigators to coregister images from two or more modalities, including microMR, microCT, microPET and optical imaging. PMID- 17721532 TI - Strategies to minimize background autofluorescence in live mice during noninvasive fluorescence optical imaging. AB - As small-animal fluorescence imaging becomes increasingly accessible to a broad spectrum of users, many lab animal researchers are just beginning to be exposed to its challenges. One setback to fluorescence imaging is background autofluorescence generated in animal tissue and in ingested food. The authors bring this issue into focus, and show how autofluorescence can be reduced in nude mice through selection of appropriate excitation wavelength and mouse diet. PMID- 17721531 TI - Multiplex fluorescent immunoassay for the simultaneous detection of serum antibodies to multiple rodent pathogens. AB - Multiplex Fluorescent Immunoassay (MFI) is a sensitive and specific serologic test that allows simultaneous detection of antibodies to multiple viral and bacterial agents in a single reaction well. MFI is a high-throughput assay that offers several advantages over other prevalent assays, and some research animal diagnostic laboratories have adopted it as their primary technique. The authors present a detailed review of MFI and its application to laboratory animal diagnostics. PMID- 17721533 TI - Adjusting to your new job. AB - Having done the hard work in winning your new job, you might find fitting into a new environment to be just as demanding. Don't make the common mistake of focusing solely on work and getting results. You need to pay equal attention to nurturing good relationships with your new colleagues. Here are a few more hints to help ensure that you get off to the best possible start. PMID- 17721534 TI - Bayesian inference of epistatic interactions in case-control studies. AB - Epistatic interactions among multiple genetic variants in the human genome may be important in determining individual susceptibility to common diseases. Although some existing computational methods for identifying genetic interactions have been effective for small-scale studies, we here propose a method, denoted 'bayesian epistasis association mapping' (BEAM), for genome-wide case-control studies. BEAM treats the disease-associated markers and their interactions via a bayesian partitioning model and computes, via Markov chain Monte Carlo, the posterior probability that each marker set is associated with the disease. Testing this on an age-related macular degeneration genome-wide association data set, we demonstrate that the method is significantly more powerful than existing approaches and that genome-wide case-control epistasis mapping with many thousands of markers is both computationally and statistically feasible. PMID- 17721535 TI - A gene in the multidrug and toxic compound extrusion (MATE) family confers aluminum tolerance in sorghum. AB - Crop yields are significantly reduced by aluminum toxicity on highly acidic soils, which comprise up to 50% of the world's arable land. Candidate aluminum tolerance proteins include organic acid efflux transporters, with the organic acids forming non-toxic complexes with rhizosphere aluminum. In this study, we used positional cloning to identify the gene encoding a member of the multidrug and toxic compound extrusion (MATE) family, an aluminum-activated citrate transporter, as responsible for the major sorghum (Sorghum bicolor) aluminum tolerance locus, Alt(SB). Polymorphisms in regulatory regions of Alt(SB) are likely to contribute to large allelic effects, acting to increase Alt(SB) expression in the root apex of tolerant genotypes. Furthermore, aluminum inducible Alt(SB) expression is associated with induction of aluminum tolerance via enhanced root citrate exudation. These findings will allow us to identify superior Alt(SB) haplotypes that can be incorporated via molecular breeding and biotechnology into acid soil breeding programs, thus helping to increase crop yields in developing countries where acidic soils predominate. PMID- 17721536 TI - Respiratory protein-generated reactive oxygen species as an antimicrobial strategy. AB - The evolution of the host-pathogen relationship comprises a series of invasive defensive tactics elicited by both participants. The stereotype is that the antimicrobial immune response requires multistep processes. Little is known about the primordial immunosurveillance system, which probably has components that directly link sensors and effectors. Here we found that the respiratory proteins of both the horseshoe crab and human were directly activated by microbial proteases and were enhanced by pathogen-associated molecular patterns, resulting in the production of more reactive oxygen species. Hemolytic virulent pathogens, which produce proteases as invasive factors, are more susceptible to this killing mechanism. This 'shortcut' antimicrobial strategy represents a fundamental and universal mode of immunosurveillance, which has been in existence since before the split of protostomes and deuterostomes and still persists today. PMID- 17721537 TI - Lymph node chemokines promote sustained T lymphocyte motility without triggering stable integrin adhesiveness in the absence of shear forces. AB - Lymphocyte motility in lymph nodes is regulated by chemokines, but the contribution of integrins to this motility remains obscure. Here we examined lymphocyte migration over CCR7-binding chemokines that 'decorate' lymph node stroma. In a shear-free environment, surface-bound lymph node chemokines but not their soluble counterparts promoted robust and sustained T lymphocyte motility. The chemokine CCL21 induced compartmentalized clustering of the integrins LFA-1 and VLA-4 in motile lymphocytes, but both integrins remained nonadhesive to ligands on lymphocytes, dendritic cells and stroma. The application of shear stress to lymphocytes interacting with CCL21 and integrin ligands promoted robust integrin-mediated adhesion. Thus, lymph node chemokines that promote motility and strongly activate lymphocyte integrins under shear forces fail to stimulate stable integrin adhesiveness in extravascular shear-free environments. PMID- 17721538 TI - Order causes secondary Bragg peaks in soft materials. AB - Highly ordered soft materials exhibit Bragg peaks that cannot be indexed assuming homogeneous crystal structures. Their origin has been attributed to changes in the crystal structure that are induced by the ordering process such as by application of external fields. This would restrict the use for the generation of highly ordered nano- and microstructured materials where a homogeneous crystal structure is a key requirement. Here, we demonstrate that these Bragg peaks are an inherent property of homogeneous ordered soft materials related to the finite coherence of their crystalline lattice. Their consideration allows a detailed and quantitative analysis of the diffraction patterns of seemingly unrelated materials such as lyotropic liquid-crystalline phases, mesoporous materials, colloidal dispersions, block copolymers, electrorheological fluids and photonic crystals. It further enables us to develop a concise picture of order, line density, field-induced orientation and epitaxial relations for soft-material lattices. PMID- 17721539 TI - Negative birefraction of acoustic waves in a sonic crystal. AB - Optical birefringence and dichroism are classical and important effects originating from two independent polarizations of optical waves in anisotropic crystals. Furthermore, the distinct dispersion relations of transverse electric and transverse magnetic polarized electromagnetic waves in photonic crystals can lead to birefringence more easily. However, it is impossible for acoustic waves in the fluid to show such a birefringence because only the longitudinal mode exists. The emergence of an artificial sonic crystal (SC) has significantly broadened the range of acoustic materials in nature that can give rise to acoustic bandgaps and be used to control the propagation of acoustic waves. Recently, negative refraction has attracted a lot of attention and has been demonstrated in both left-handed materials and photonic crystals. Similar to left handed materials and photonic crystals, negative refractions have also been found in SCs. Here we report, for the first time, the acoustic negative-birefraction phenomenon in a two-dimensional SC, even with the same frequency and the same 'polarization' state. By means of this feature, double focusing images of a point source have been realized. This birefraction concept may be extended to other periodic systems corresponding to other forms of waves, showing great impacts on both fundamental physics and device applications. PMID- 17721540 TI - Quantum-spin-liquid states in the two-dimensional kagome antiferromagnets ZnxCu4 x(OD)6Cl2. AB - A three-dimensional system of interacting spins typically develops static long range order when it is cooled. If the spins are quantum (S=1/2), however, novel quantum paramagnetic states may appear. The most highly sought state among them is the resonating-valence-bond state, in which every pair of neighbouring quantum spins forms an entangled spin singlet (valence bonds) and these singlets are quantum mechanically resonating among themselves. Here we provide an experimental indication for such quantum paramagnetic states existing in frustrated antiferromagnets, Zn(x)Cu(4-x)(OD)(6)Cl(2), where the S=1/2 magnetic Cu2+ moments form layers of a two-dimensional kagome lattice. We find that in Cu(4)(OD)(6)Cl(2), where distorted kagome planes are weakly coupled, a dispersionless excitation mode appears in the magnetic excitation spectrum below approximately 20 K, whose characteristics resemble those of quantum spin singlets in a solid state, known as a valence-bond solid, that breaks translational symmetry. Doping with non-magnetic Zn2+ ions reduces the distortion of the kagome lattice, and weakens the interplane coupling but also dilutes the magnetic occupancy of the kagome lattice. The valence-bond-solid state is suppressed, and for ZnCu(3)(OD)(6)Cl(2), where the kagome planes are undistorted and 90% occupied by the Cu2+ ions, the low-energy spin fluctuations become featureless. PMID- 17721541 TI - Femtosecond modification of electron localization and transfer of angular momentum in nickel. AB - The rapidly increasing information density required of modern magnetic data storage devices raises the question of the fundamental limits in bit size and writing speed. At present, the magnetization reversal of a bit can occur as quickly as 200 ps (ref. 1). A fundamental limit has been explored by using intense magnetic-field pulses of 2 ps duration leading to a non-deterministic magnetization reversal. For this process, dissipation of spin angular momentum to other degrees of freedom on an ultrafast timescale is crucial. An even faster regime down to 100 fs or below might be reached by non-thermal control of magnetization with femtosecond laser radiation. Here, we show that an efficient novel channel for angular momentum dissipation to the lattice can be opened by femtosecond laser excitation of a ferromagnet. For the first time, the quenching of spin angular momentum and its transfer to the lattice with a time constant of 120+/-70 fs is determined unambiguously with X-ray magnetic circular dichroism. We report the first femtosecond time-resolved X-ray absorption spectroscopy data over an entire absorption edge, which are consistent with an unexpected increase in valence-electron localization during the first 120+/-50 fs, possibly providing the driving force behind femtosecond spin-lattice relaxation. PMID- 17721542 TI - Bright far-red fluorescent protein for whole-body imaging. AB - For deep imaging of animal tissues, the optical window favorable for light penetration is in near-infrared wavelengths, which requires proteins with emission spectra in the far-red wavelengths. Here we report a far-red fluorescent protein, named Katushka, which is seven- to tenfold brighter compared to the spectrally close HcRed or mPlum, and is characterized by fast maturation as well as a high pH-stability and photostability. These unique characteristics make Katushka the protein of choice for visualization in living tissues. We demonstrate superiority of Katushka for whole-body imaging by direct comparison with other red and far-red fluorescent proteins. We also describe a monomeric version of Katushka, named mKate, which is characterized by high brightness and photostability, and should be an excellent fluorescent label for protein tagging in the far-red part of the spectrum. PMID- 17721543 TI - Higher-energy C-trap dissociation for peptide modification analysis. AB - Peptide sequencing is the basis of mass spectrometry-driven proteomics. Here we show that in the linear ion trap-orbitrap mass spectrometer (LTQ Orbitrap) peptide ions can be efficiently fragmented by high-accuracy and full-mass-range tandem mass spectrometry (MS/MS) via higher-energy C-trap dissociation (HCD). Immonium ions generated via HCD pinpoint modifications such as phosphotyrosine with very high confidence. Additionally we show that an added octopole collision cell facilitates de novo sequencing. PMID- 17721544 TI - High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. AB - In thalassemia, deficient globin-chain production during erythropoiesis results in anemia. Thalassemia may be further complicated by iron overload (frequently exacerbated by blood transfusion), which induces numerous endocrine diseases, hepatic cirrhosis, cardiac failure and even death. Accumulation of iron in the absence of blood transfusions may result from inappropriate suppression of the iron-regulating peptide hepcidin by an erythropoietic mechanism. To test this hypothesis, we examined erythroblast transcriptome profiles from 15 healthy, nonthalassemic donors. Growth differentiation factor 15 (GDF15), a member of the transforming growth factor-beta superfamily, showed increased expression and secretion during erythroblast maturation. Healthy volunteers had mean GDF15 serum concentrations of 450 +/- 50 pg/ml. In comparison, individuals with beta thalassemia syndromes had elevated GDF15 serum levels (mean 66,000 +/- 9,600 pg/ml; range 4,800-248,000 pg/ml; P < 0.05) that were positively correlated with the levels of soluble transferrin receptor, erythropoietin and ferritin. Serum from thalassemia patients suppressed hepcidin mRNA expression in primary human hepatocytes, and depletion of GDF15 reversed hepcidin suppression. These results suggest that GDF15 overexpression arising from an expanded erythroid compartment contributes to iron overload in thalassemia syndromes by inhibiting hepcidin expression. PMID- 17721546 TI - Broad HIV-1 neutralization mediated by CD4-binding site antibodies. AB - We have identified several patient sera showing potent and broad HIV-1 neutralization. Using antibody adsorption and elution from selected gp120 variants, the neutralizing specificities of the two most broadly reactive sera were mapped to the primary receptor CD4-binding region of HIV-1 gp120. Novel antibodies to the CD4-binding site are elicited in some HIV-1-infected individuals, and new approaches to present this conserved region of gp120 to the immune system may result in improved vaccine immunogens. PMID- 17721547 TI - A ligand-receptor fusion of growth hormone forms a dimer and is a potent long acting agonist. AB - Cytokine hormones have a short plasma half-life and require frequent administration. For example, growth hormone replacement involves daily injections. In common with other cytokines, the extracellular domain of the growth hormone receptor circulates as a binding protein, which naturally prolongs the biological half-life of growth hormone. Here we have studied the biological actions of a ligand-receptor fusion of growth hormone and the extracellular domain of its receptor. The genetically engineered ligand-receptor fusion protein was purified from mammalian cell culture. In rats, the ligand-receptor fusion had a 300-times reduced clearance as compared to native growth hormone, and a single injection promoted growth for 10 d, far exceeding the growth seen after administration of native growth hormone. The ligand-receptor fusion forms a reciprocal, head-to-tail dimer that provides a reservoir of inactive hormone similar to the natural reservoir of growth hormone and its binding protein. In conclusion, a ligand-receptor fusion of cytokine to its extracellular receptor generates a potent, long-acting agonist with exceptionally slow absorption and elimination. This approach could be easily applied to other cytokines. PMID- 17721548 TI - F1-ATPase rotates by an asymmetric, sequential mechanism using all three catalytic subunits. AB - F1-ATPase, the catalytic part of FoF1-ATP synthase, rotates the central gamma subunit within the alpha3beta3 cylinder in 120 degrees steps, each step consuming a single ATP molecule. However, how the catalytic activity of each beta subunit is coordinated with the other two beta subunits to drive rotation remains unknown. Here we show that hybrid F1 containing one or two mutant beta subunits with altered catalytic kinetics rotates in an asymmetric stepwise fashion. Analysis of the rotations reveals that for any given beta subunit, the subunit binds ATP at 0 degrees, cleaves ATP at approximately 200 degrees and carries out a third catalytic event at approximately 320 degrees. This demonstrates the concerted nature of the F1 complex activity, where all three beta subunits participate to drive each 120 degrees rotation of the gamma subunit with a 120 degrees phase difference, a process we describe as a 'sequential three-site mechanism'. PMID- 17721545 TI - Platelet CD36 links hyperlipidemia, oxidant stress and a prothrombotic phenotype. AB - Dyslipidemia is associated with a prothrombotic phenotype; however, the mechanisms responsible for enhanced platelet reactivity remain unclear. Proatherosclerotic lipid abnormalities are associated with both enhanced oxidant stress and the generation of biologically active oxidized lipids, including potential ligands for the scavenger receptor CD36, a major platelet glycoprotein. Using multiple mouse in vivo thrombosis models, we now demonstrate that genetic deletion of Cd36 protects mice from hyperlipidemia-associated enhanced platelet reactivity and the accompanying prothrombotic phenotype. Structurally defined oxidized choline glycerophospholipids that serve as high-affinity ligands for CD36 were at markedly increased levels in the plasma of hyperlipidemic mice and in the plasma of humans with low HDL levels, were able to bind platelets via CD36 and, at pathophysiological levels, promoted platelet activation via CD36. Thus, interactions of platelet CD36 with specific endogenous oxidized lipids play a crucial role in the well-known clinical associations between dyslipidemia, oxidant stress and a prothrombotic phenotype. PMID- 17721549 TI - YY1 functions with INO80 to activate transcription. AB - Ubiquitously expressed transcription factor Yin-Yang-1 (YY1) controls expression of many genes. YY1 is tightly associated with the human ATP-dependent INO80-like chromatin-remodeling complex (INO80). INO80 is recruited by YY1 to YY1-activated genes, where it functions as an essential coactivator. Binding of YY1 to its DNA sites in target genes requires INO80, suggesting that YY1 uses the INO80 complex not only to activate transcription but also to gain access to target promoters. PMID- 17721550 TI - Negative inotropic effects of endothelin-1 in mouse cardiomyocytes: evidence of a role for Na+-Ca2+ exchange. AB - Endothelin-1 (ET-1) is a peptide hormone produced within the myocardium which may modulate myocardial contractility in a paracrine-autocrine fashion. In the majority of species, ET-1 has a direct positive inotropic effect on the myocardium that involves both increased myofilament Ca(2+) sensitivity and increased Ca(2+) transients. Ca(2+) entry through reverse-mode Na(+)-Ca(2+) exchange, involving both indirect effects via elevation of intracellular [Na(+)] and direct activation of the Na(+)-Ca(2+) exchanger, have been suggested to contribute to the increase in Ca(2+) transients. Conversely, mouse cardiomyocytes show an exclusively negative inotropic response to ET-1. Here, Nishimaru and colleagues present novel evidence that the negative inotropic effect of ET-1 in mouse cardiomyocytes involves both a reduction in myofilament Ca(2+) sensitivity and increased Ca(2+) extrusion, via Na(+)-Ca(2+) exchange. Data obtained using the selective Na(+)-Ca(2+) exchange blocker, SEA0400, suggest that a re assessment of the role of the exchanger in Ca(2+)-handling by mouse cardiomyocytes may be necessary. PMID- 17721551 TI - Prostamides (prostaglandin-ethanolamides) and their pharmacology. AB - The prostamides are part of a large and continually expanding series of pharmacologically unique neutral lipids. They are COX-2 derived oxidation products of the endocannabinoid/endovanniloid anandamide. Prostamide pharmacology is unique and, as in the case of the endocannabinoids anandamide and 2 arachidonylglycerol, bears little resemblance to that of the corresponding free acids. By virtue of its close relationship to the anti-glaucoma drug bimatoprost, prostamide F(2alpha) has received the greatest research attention. Prostamide F(2alpha) and bimatoprost effects appear independent of prostanoid FP receptor activation, according to a litany of agonist studies. Studies involving freshly isolated and separate feline iridial smooth muscle cells revealed that bimatoprost and FP receptor agonists stimulated different cells, without exception. This suggests the existence of receptors that preferentially recognize prostamide F(2alpha). The recent discovery of prostamide antagonists has provided further support for prostamide receptors as discrete entities. The prototypical prostamide antagonists, AGN 204396 and 7, blocked the effects of prostamide F(2alpha) and bimatoprost but not those of PGF(2alpha) and FP receptor agonists in the feline iris. Second generation more potent prostamide antagonists, such as AGN 211334, should allow the role of prostamides in health and disease to be elucidated. From the therapeutics standpoint, the prostamide F(2alpha) analogue bimatoprost is the most efficacious ocular hypotensive agent currently available for the treatment of glaucoma. PMID- 17721552 TI - Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction. AB - BACKGROUND AND PURPOSE: Monoamine oxidase inhibitors (MAOI) are known to cause serotonin toxicity (ST) when administered with selective serotonin reuptake inhibitors (SSRI). Methylene blue (methylthionium chloride, MB), a redox dye in clinical use, has been reported to precipitate ST in patients using SSRI. MB was assessed for MAO inhibition and so for its potential to precipitate ST. EXPERIMENTAL APPROACH: Inhibition of purified human MAO was quantified using kinetic assays and visible spectral changes to study the interactions of MB with MAO A. KEY RESULTS: MB was a potent (tight binding) inhibitor for MAO A. It also inhibited MAO B but at much higher concentration. Interactions of MB with the active site of MAO A were confirmed by its action both as an oxidising substrate and as a one-electron reductant. CONCLUSIONS AND IMPLICATIONS: MB is a potent reversible inhibitor of MAO A with implications for gut uptake of amines when administered orally. At concentrations reported in the literature after intravenous administration, MAO B would be partially inhibited but MAO A would be completely inhibited. This inhibition of MAO A would be expected to lead to perturbations of 5-hydroxytryptamine metabolism and hence account for ST occurring when administered to patients on SSRI treatment. PMID- 17721555 TI - Comparative study of epidural administration of 10 ml of 0.1% bupivacaine with 2 mg butorphanol and 10 ml of 0.25% plain bupivacaine for analgesia during labor. AB - Analgesia during labor provided by two epidural drug regimens was compared in a double blind, randomized, prospective study. Group A (n = 12) received 10 ml bolus doses of 0.1% bupivacaine with butorphanol 2 mg while Group B (n = 8) received 10 ml of 0.25% plain bupivacaine. The objectives of this study was to compare, between the quality of an epidural labor analgesia using initial loading dose of 0.1% bupivacaine and 2 mg butorphanol with a initial loading dose of 0.25% bupivacaine. In Group A, incidence of motor block was 8.3% and that of prolong 2nd stage of labor was 16.7%, both were decreased in comparison with Group B, although they were not statistically significant. Hemodynamic variables were stable and no adverse neonatal and maternal outcome was observed in both groups. Addition of butorphanol to bupivacaine may be safe alternative to reduce motor block and decrease prolong 2nd stage for epidural labor analgesia. PMID- 17721556 TI - Acute mushroom poisoning : a report of 41 cases. AB - A retrospective analysis of all mushroom poisoning cases admitted in Tansen Mission Hospital in the period of two months of the year 2005 was done. Forty-one cases were admitted during that period, among which only 34 case records could be found for analysis. Female (58.82%) outnumbered the male and 15 (44.11%) of the cases were from pediatric age group. The poisoning was secondary to consumption of different species of Amanita variety including the most poisonous Amanita phalloides. The commonest symptoms at the time of presentation in both adults and children was gastrointestinal (diarrhea, vomiting and abdominal pain). There were 12 mortalities and they died at the median interval of 3.5 days after admission. The main cause of death was acute liver failure and acute renal failure. Relative risk of having a bad outcome was found to be higher when the mushroom was consumed with alcohol when compared with non-alcoholics. High mortality was probably due to late presentation and only the conservative management in all the cases. Increased community and medical awareness is needed to reduce the frequency, morbidity and mortality of mushroom poisoning. PMID- 17721553 TI - Identification of domains influencing assembly and ion channel properties in alpha 7 nicotinic receptor and 5-HT3 receptor subunit chimaeras. AB - BACKGROUND AND PURPOSE: Nicotinic acetylcholine receptors (nAChRs) and 5 hydroxytryptamine type 3 receptors (5-HT(3)Rs) are members of the superfamily of neurotransmitter-gated ion channels. Both contain five subunits which assemble to form either homomeric or heteromeric subunit complexes. With the aim of identifying the influence of subunit domains upon receptor assembly and function, a series of chimaeras have been constructed containing regions of the neuronal nAChR alpha 7 subunit and the 5-HT(3) receptor (3A) subunit. EXPERIMENTAL APPROACH: A series of subunit chimaeras containing alpha 7 and 5-HT(3A) subunit domains have been constructed and expressed in cultured mammalian cells. Properties of the expressed receptors have been examined by means of radioligand binding, agonist-induced changes in intracellular calcium and patch-clamp electrophysiology. KEY RESULTS: Subunit domains which influence properties such as rectification, desensitization and conductance have been identified. In addition, the influence of subunit domains upon subunit folding, receptor assembly and cell-surface expression has been identified. Co-expression studies with the nAChR-associated protein RIC-3 revealed that, in contrast to the potentiating effect of RIC-3 on alpha 7 nAChRs, RIC-3 caused reduced levels of cell-surface expression of some alpha 7/5-HT(3A) chimaeras. CONCLUSIONS AND IMPLICATIONS: Evidence has been obtained which demonstrates that subunit transmembrane domains are critical for efficient subunit folding and assembly. In addition, functional characterization of subunit chimaeras revealed that both extracellular and cytoplasmic domains exert a dramatic and significant influence upon single-channel conductance. These data support a role for regions other than hydrophobic transmembrane domains in determining ion channel properties. PMID- 17721557 TI - Breastfeeding in Nepal: patterns and determinants. AB - The aim of this study was to investigate the determinants of breast-feeding according to the characteristics of mother and her child. Cox proportional hazard model technique has been employed to investigate the determinants of breast feeding. The data were utilized from a sample survey of Palpa and Rupandehi districts of rural Nepal. The study revealed that the current age of mothers, their education and socio-economic status were found to be the main determinants of breast-feeding. The current age of mother showed statistically significant relation with the duration of breast-feeding. Younger mothers are most likely to terminate breast-feeding early as compared to older counter-parts. The decreased risk of terminating breast-feeding was found with increased duration of post partum amenorrhea, and a strong positive association was found to be statistically significant. The increased relative risk of terminating breast feeding was found with increased the level of education of mothers, which indicates that the education is inversely related to the duration of breast feeding. For instance, three times higher risk of terminating breast-feeding was found for educated mothers as compared to illiterate mothers. Socio-economic status of the household exhibits a statistically significant effect on the duration of breast-feeding. It is believed that this finding may help planners and policy-makers for designing proper policy and program for improving mothers and their children's health and for reducing fertility of a country. PMID- 17721558 TI - Prevalence of complications of simple tooth extractions and its comparison between a tertiary center and peripheral centers: a study conducted over 8,455 tooth extractions. AB - This study was conducted to investigate and compare the prevalence of complications of simple tooth extractions in a tertiary centre (BP Koirala Institute of Health Sciences, Dharan) and the peripheral centers (Mechi and Koshi zonal hospitals). This is a prospective descriptive study. Tooth extractions were carried out under local anesthesia in the tertiary and the peripheral centers during one year period (March 15"th 2004 to March H"111 2005). Intraoperative and postoperative complications were recorded and analyzed. Out of 8,455 tooth extractions in 6,639 [male-2,465 (37.12%) and females - 4,174 (62.88%)] patients aged between 5yrs- 65 yrs, 7,152 extractions were done in tertiary center and 1,393 extractions were done in peripheral centers.90 complications (1.06%) were observed. 53(58.89%) complications were intraoperative and 37(41.12%) complications were postoperative. 60(0.84%) complications were observed in the tertiary center and 30 (2.3%) complications were observed in the peripheral centers and the difference was highly significant (P<0.000001). The most frequent complication in the tertiary centre was fracture of tuberosity (0.15%) and in the peripheral centers it was 'roots left' (0.77%). Prevalence of 'roots left', injury to adjacent tooth and postoperative hemorrhage was significantly high (P<0.05) in peripheral centers. The higher prevalence rate of complications of tooth extractions in the peripheral centers should not be overlooked and well equipped and organized extraction procedure with qualified dental practitioner is strongly suggested to minimize the complications. PMID- 17721559 TI - Study of plasma lipid and lipoprotein profile in elite women boxers during a six weeks' training progamme. AB - The present study was undertaken with an objective to frame out the lipid profile of Indian Women Boxers. Women boxing is a newly recognized game and no work has been reported on elite female boxers in India till date. The study was based on a sample of 45 women boxers (age 17 ~ 24 years) attending Senior National Women Boxing Camp at Sports Authority of India. Each subject was evaluated for Lipid Profile variables at the beginning and end of the six weeks training camp. Fasting blood samples were taken from the antecubital vein by venipuncture. Before the samples drawn the subjects were asked to take rest for ten minutes. The blood sample was analyzed by HITACHI UV-2000 spectrophotometer (Japan). Standard techniques and procedures were followed for all the estimation. Volume and intensity of different components of training was measured by observational and physiological methods. Data were subjected to statistical treatment like mean and standard deviation. Test of significance't' - test (for paired sample) was applied to asses the difference in pre & post-test. Results reveal that mean (+/ SD) Cholesterol, Triglyceride, LDL, HDL - Cholesterol and Cholesterol / HDL Cholesterol ratio was 144.7 +/- 3.6 mg%, 59.7 +/- 17.5 mg% 81.4 +/- 21.1 mg% 51.3 +/- 8.2 mg% and 2.8 +/- 0.5 respectively as found in the pre-test. Significant difference (P < 0.01) was observed in Cholesterol, LDL-Cholesterol, HDL Cholesterol level in the post-test. The study concludes that women who practice sport of boxing on regular basis have a favorable lipid profile. A significant change in lipid profile of the boxers was observed after 6 weeks' training program. PMID- 17721561 TI - Complex elbow dislocation with ipsilateral segmental fracture of radius and ulna in a young boy: a complex injury with multiple fractures. AB - Complex elbow dislocation1 (fracture of lateral condyle and avulsion fracture of medial epicondyle) with ipsilateral segmental fracture of radius and ulna without distal neurovascular deficit following machinery rolling belt injury in a 14 years boy presenting to emergency room of BP Koirala Institute of Health Sciences, is reported due to its complex nature of injury and good outcome after adequate follow up. The literature is reviewed for complex elbow dislocation to show its rarity. PMID- 17721560 TI - Factors influencing mortality in perforated duodenal ulcer following emergency surgical repair. AB - Duodenal perforation is a common abdominal catastrophe with excellent outcome if prompt resuscitation and surgical repair of perforation are done. The aim of this study was to identify factors associated with death after surgery in patients with duodenal perforation. One hundred and forty-five patients who underwent Graham's patch repair for perforated duodenal ulcer between 14 April 2002 and 31 December 2004 were studied. The mean age was 45.99 years and 61 patients (42.07 %) were referrals. There were 124 (85.52 %) males and 21 (14.48 %) females. There were 10 deaths (6.9 %). The mean time delay was 2.46 days. It was 2.37 days in survivors, 3.7 days in non-survivors. The time delay was 3.25 days for females and 3.13 days for patients referred from another hospital. The mortality was significantly associated with time delay between perforation and operation (p<0.01), presence of co-morbid conditions (P<0.04), respiratory rate (p<0.02), raised blood urea (p<0.01) and serum creatinine (p<0.001), size of perforation (p<0.005), amount of peritoneal fluid (p=0.003) and requirement of postoperative intensive care unit support (p=0.003). Time delay between perforation and operation, preoperative blood urea and serum creatinine, size of perforation and amount of peritoneal fluid, presence of co-morbid conditions and need for post operative ICU support are the important predictors of outcome after emergency surgery for duodenal perforation. PMID- 17721562 TI - Multiple granular cell tumor of the esophagus treated endoscopically. AB - Granular cell tumor (GCT) of esophagus is a rare lesion, usually found incidentally during upper gastrointestinal endoscopic examination undertaken for another reasons. The origin of this neoplasm is still unclear but no organ seems to be immune to this neoplasm. Although most of the lesions are benign, few reports of malignant GCT, synchronous as well as metachronous, are also reported. It can occur at any age, but are most commonly observed in fourth and fifth decade of life. We herein report a case of multiple GCT treated by endoscopic mucosal resection and review the relevant literatures. PMID- 17721563 TI - Takotsubo disease. AB - Tako-tsubo cardiomyopathy, a novel heart syndrome with peculiar variant of left ventricular dysfunction, characterized by preferential apical dyskinesis and basal hyper contractility has been described on numerous occasions especially in persons without obstructive coronary artery disease. It is considered of reversible etiology and seems to have increased predisposition in elderly, stress ridden females. Although Tako-tsubo cardiomyopathy was described initially in patients of Japanese origin, its existence in white populations in both Europe and the US have recently been documented. Simultaneous multivessel coronary spasm of the epicardial coronary microvessels is believed to be a major contributor. However, this pathophysiologic basis for this phenomenon has not been validated universally throughout literature. Another potential mechanism of events that seems to be responsible for this phenomenon is the transient myocardial stunning associated with hypersensitivity to catecholamine. The clinical presentation usually simulates that of an acute ST- elevated myocardial infarction but the coronary angiography by definition shows no critical lesions. Patients surviving acute episode usually recover fully in few weeks. Acute onset of cardiogenic shock in a person without coronary risk factors should raise the possibility of this rare type of entity but should not withhold the acute treatment. Prognosis generally varies and has largely been good. Takotsubo though largely benign may be fatal sometimes. PMID- 17721564 TI - Rural hospital medicine in New Zealand: vocational registration and the recognition of a new scope of practice. AB - Establishing a professional body for rural hospital generalist doctors was identified as a priority by the Rural Hospital Doctors Working Party which was formed in July 2005. In May 2006 the Working Party lodged an application with the Medical Council of New Zealand (MCNZ) for Branch Advisory Body status and the recognition of rural hospital medicine as a new scope of practice. The Branch Advisory Body will sit within the Royal New Zealand College of General Practitioners. It will have an independent Board of Studies which will administer vocational training and reaccreditation programmes for these doctors. These initiatives represent an opportunity to generate the skilled generalist medical workforce NZ rural hospitals need to move into the future. The application is currently before the MCNZ, and a final decision is expected later this year. This paper outlines some of the main points contained in the application document. PMID- 17721565 TI - Medical opportunity of special scale? The future of rural hospitals in New Zealand? PMID- 17721566 TI - Three students exposed to Uraba lugens (gum leaf skeletoniser) caterpillars in a West Auckland school. PMID- 17721567 TI - Heracleum mantegazzianum and Toxicodendron succedaneum: plants of human health significance in New Zealand and the National Pest Plant Accord. AB - New Zealand's National Pest Plant Accord (NPPA) is a voluntary and cooperative agreement between industry, regional councils, and central government departments with biosecurity responsibilities (primarily the Ministry of Agriculture and Forestry and the Department of Conservation). Plant species included in the NPPA are declared unwanted organisms under the Biosecurity Act 1993, which prevents their sale, propagation, or distribution across the country. Although MAF Biosecurity New Zealand (the lead agency in New Zealand's biosecurity system) has evaluated the potential human health impacts of 202 species considered for inclusion in the NPPA, two species were examined primarily due to their significance to human health: Heracleum mantegazzianum (giant hogweed, cow parsnip, wild parsnip) and Toxicodendron succedaneum (rhus tree, wax tree, Japanese wax tree). As a result of this process, H. mantegazzianum has been listed in the NPPA. In contrast, T. succedaneum was not included in the NPPA, as the latter was deemed to be an inappropriate mechanism for its control. In this article the NPPA process is outlined, and the adverse impacts on human health of these two species are discussed--including symptoms, treatment, and possible management measures. PMID- 17721568 TI - Phytophotodermatitis caused by contact with a fig tree (Ficus carica). AB - Two arborists presented acutely with blistering eruptions affecting their forearms, hands, and fingers. The previous day, both men had pruned branches from a large fig tree, Ficus carica, which had sustained damaged during a storm. The following morning, both complained of a burning discomfort which rapidly evolved into erythema and bullae on skin that had been in direct contact with the tree branches. These symptoms gradually resolved over 4 to 6 weeks. Although phytophotodermatitis from Ficus carica has been reported, it is often poorly recognised and there is a need to raise awareness amongst arborists, orchardists, forestry workers, gardeners, and health professionals. PMID- 17721569 TI - Fatal dog bites in New Zealand. AB - AIMS: To examine fatalities from dog bites in New Zealand and review New Zealand's most recent fatalities, and the commonalities they show with dog attacks both in New Zealand and overseas. METHODS: Information was collated from past studies, international reviews, and press coverage and then summarised. This information was then applied and added to a forensic review of the dog bite related fatality recorded in 2004 in Dunedin. CONCLUSIONS: Dogs are no different the world over. There have been five confirmed dog bite-related fatalities in New Zealand. Dog attacks in New Zealand strongly resemble those from other developed countries. Indeed similar situations increase the odds of an attack. Awareness of these situations may make avoidance of dog bites easier. PMID- 17721570 TI - Routine 'Health of the Nation Outcome Scales for elderly people' (HoNOS65+) collection in an acute psychogeriatric inpatient unit in New Zealand. AB - INTRODUCTION: HoNOS (Health of the Nation Outcomes Scale) is an outcome measure used by mental health professionals aiming to give a snapshot of a person's psychiatric symptoms and psychosocial functioning. AIM: HoNOS65+ was introduced as a routine outcome measure in our service as part of the New Zealand Mental Health Standard Measures of Assessment and Recovery Outcomes Initiative. The aim of this paper is to report the findings from the use of this tool in our acute psychogeriatric inpatient unit. METHOD: This is a retrospective analysis of the HoNOS database from 2002 to 2005. Service users were classified into two groups (organic disorders and functional disorders) according to their ICD-10 clinical coding diagnoses. Statistical analysis was performed to compare the HoNOS65+ scores at admission and discharge within each group. RESULTS: There were 431 start episodes and 452 end episodes completed. However, only 130 of these episodes were matched and were usable in this analysis. 29(21%) service users with diagnoses of organic disorders and 101(72%) with diagnoses of functional disorders. The mean total HoNOS65+ score reduced significantly for both groups from admission (organic: 16.45; functional: 14.00) to discharge (organic: 12.34; functional: 8.76). For the organic group, significant improvement was observed in 2 (behaviour and symptoms) subscales; and for the functional group, significant improvement was observed in 3 (behaviour, impairment, and symptoms) subscales. CONCLUSION: The findings provide objective evidence to support the clinical impression that psychogeriatric inpatient treatment is an effective intervention for both organic and functional disorders. We identified a lack of improvement in the social subscale for both groups. The social subscale scores on admission were relatively low and the lack of improvement might be because specific interventions were not necessary during the inpatient episode. Further exploration of this subscale would be useful in clarifying whether there is a need to plan service development to address these aspects of service users' care during the acute admission phase. PMID- 17721572 TI - New hospital consultant: surviving a difficult period. AB - The first years of consultant practice are amongst the most stressful in a medical specialist's career. Recognising the likely difficulties is essential if measures are to be put in place to lessen their impact. In this article, recommendations are made on how to balance clinical and non-clinical duties and to obtain the support required for professional development. Self-care of mental and physical health is vital and planning is necessary to ensure that both personal health and a work/life balance are maintained. PMID- 17721571 TI - Murine typhus: a newly recognised problem in the Waikato region of New Zealand. AB - AIM: To characterise and investigate patients diagnosed with murine typhus in the Waikato District Health Board (DHB) region during 2006. METHOD: We reviewed the hospital and general practitioner records of all patients presenting with clinical and serological evidence of murine typhus. All patients were interviewed by telephone using a semi-structured questionnaire to identify environmental risk factors for infection. A limited, retrospective serosurvey was undertaken and surveillance was enhanced. RESULTS: 12 patients were identified, all had either lived, or spent considerable time, in rural areas; 7 patients had seen rats on their properties 'regularly' and 3 remembered fleabites within the incubation period of the illness. The classic triad of symptoms is fever, headache, and rash -these symptoms were seen in 12, 11, and 8 patients respectively; lethargy, myalgias, nausea, and vomiting were also common. 11 patients had abnormal liver function tests at presentation, and 7 had low platelets. Treatment with doxycycline was associated with a shorter hospital stay. CONCLUSION: Murine typhus has now been confirmed in rural areas throughout the Waikato DHB region. Rats are likely associated with disease in rural communities and rat control is a complex issue. However, a greater awareness of the disease should lead to earlier diagnosis and treatment. PMID- 17721573 TI - Medical Image. What is wrong with my right arm and leg? PMID- 17721574 TI - Cheaper than chicken: protein foods ranked by supermarket prices. PMID- 17721575 TI - Criticism of the decision not to fund the HPV vaccine for pre-adolescent females in New Zealand, and response. PMID- 17721576 TI - Self-applied treatment of persistent plantar wart with 5% imiquimod cream. PMID- 17721577 TI - Normal vaginal deliveries. PMID- 17721578 TI - Prevalence of new and known diabetes mellitus, impaired glucose tolerance, and impaired fasting glucose. PMID- 17721579 TI - PHARMAC's funding of 9 weeks Herceptin: many assumptions in a high-risk decision. PMID- 17721580 TI - Formation of direct metal-metal bonds from 16-electron "pseudo-aromatic" half sandwich complexes Cp''M[E2C2(B10H10)]. AB - Continuous study on preparation of multimetallic clusters is stimulated by their rich coordination chemistry and promising applications in a variety of interesting fields. Although numerous efforts have been devoted to this field, the rational design of homo- and hetero-multimetallic compounds with direct metal metal bonding supported by 1,2-dicarba-closo-dodecarborane-1,2-dichalcogenolates will still be an important step forward. This tutorial review focuses on the synthetic approach via redox reactions between the pseudo-aromatic half-sandwich oraganometallic carborane precursors and low-valent transition metal reagents. The tailoring of reaction conditions and the structural information from the resulting products are discussed extensively. PMID- 17721581 TI - Recent advances in the chemistry of magnesium carbenoids. AB - This tutorial review deals with recent advances in the chemistry and synthetic use of magnesium carbenoids. The reactivity of traditional carbenoids (alpha haloalkyllithium species) was successfully reduced by using magnesium as the metal instead of lithium. Properties of these relatively stable carbenoids, magnesium carbenoids, were widely investigated and it was found that the magnesium carbenoids have very interesting reactivity toward several nucleophiles. The magnesium carbenoids, magnesium cyclopropylidenes, magnesium alkylidene carbenoids, and magnesium beta-oxido carbenoids are generated from alpha-chloroalkyl (or alpha-chloroalkenyl) aryl sulfoxides with a Grignard reagent at low temperature by sulfoxide-magnesium exchange reaction. The stability of the generated magnesium carbenoids and several new reactions based on the electrophilicity of the magnesium carbenoids, including 1,3-CH insertion, are reviewed. Magnesium carbenoids open up the new world of the chemistry of carbenoids. PMID- 17721583 TI - The Baylis-Hillman reaction: a novel source of attraction, opportunities, and challenges in synthetic chemistry. AB - The Baylis-Hillman reaction is a successful, useful, and atom-economical carbon carbon bond forming reaction, which has grown from an obscure level to the level of high synthetic popularity due to its operational simplicity and also due to the enormous applications of the Baylis-Hillman adducts in organic synthesis. In this tutorial review, we briefly describe the way this reaction has grown to its present heights and the opportunities, attractions, and challenges the reaction offers with respect to its asymmetric and intramolecular versions, and mechanistic aspects. PMID- 17721582 TI - Synthesis of functionalized biodegradable polyesters. AB - This tutorial review summarizes recent developments in the syntheses of functionalized aliphatic polyesters. These polymers are attracting attention as sustainable alternatives to petrochemicals and for applications in medicine. Two main syntheses are described: step polymerization using mild chemo/enzymatic catalysis and ring opening polymerization, which is usually initiated by metal complexes. The methods are compared and their utility illustrated with reference to interesting new materials. PMID- 17721584 TI - Chromium arene complexes in organic synthesis. AB - The complexation of an arene to a chromium tricarbonyl unit changes its chemical behavior, giving rise to unprecedented transformations. The electron-withdrawing effect of the unit allows efficient nucleophilic attack (S(N)Ar and dearomatization reactions), stabilizes negative charges in benzylic positions and activates C(Ar)-halogen bonds for cross-coupling reactions. In addition, the Cr(CO)(3) moiety exerts great facial control so it can be used as an auxiliary that can easily be removed. The 1,2- and 1,3-unsymmetrically disubstituted complexes are planar chiral and there are various ways to prepare them in enantiomerically pure form. Planar chiral chromium complexes are becoming useful intermediates and ligands for asymmetric catalysis. This mature field of organometallic chemistry has given rise to several synthetic applications of chromium arene complexes in the synthesis of natural products. This chemistry is overviewed in this tutorial review, giving special attention to the most recent and outstanding contributions in the area. PMID- 17721585 TI - The surface of cultural heritage artefacts: physicochemical investigations for their knowledge and their conservation. AB - This tutorial review intends to show, through demonstrative examples chosen from the recent literature, how surface characterisation conducted by modern investigation methods leads to very rich information on a cultural heritage artefact's history, fabrication techniques and conservation state. Application of surface science to conservation science is of great help for the definition of a conservation and restoration policy for museum and archaeological objects. A brief description of the investigation methods is given, together with relevant references for more detailed information. PMID- 17721586 TI - The single molecular precursor approach to metal telluride thin films: imino bis(diisopropylphosphine tellurides) as examples. AB - Interest in metal telluride thin films as components in electronic devices has grown recently. This tutorial review describes the use of single-source precursors for the preparation of metal telluride materials by aerosol-assisted chemical vapour deposition (AACVD) and acquaints the reader with the basic techniques of materials characterization. The challenges in the design and synthesis of suitable precursors are discussed, focusing on metal complexes of the recently-developed imino-bis(diisopropylphosphine telluride) ligand. The generation of thin films and nanoplates of CdTe, Sb(2)Te(3) and In(2)Te(3) from these precursors are used as illustrative examples. PMID- 17721587 TI - Atypical compounds of gases, which have been called 'noble'. AB - In this critical review I describe fascinating experimental and theoretical advances in 'noble gas' chemistry during the last twenty years, and have taken a somewhat unexpected course since 2000. I also highlight perspectives for further development in this field, including the prospective synthesis of compounds containing as yet unknown Xe-element and element-Xe-element bridging bonds, peroxide species containing Xe, adducts of XeF(2) with various metal fluorides, Xe-element alloys, and novel pressure-stabilized covalently bound and host-guest compounds of Xe. A substantial part of the essay is devoted to the-as yet experimentally unexplored-behaviour of the compounds of Xe under high pressure. The blend of science, history, and theoretical predictions, will be valued by inorganic and organic chemists, materials scientists, and the community of theoretical and experimental high-pressure physicists and chemists (151 references). PMID- 17721588 TI - Catalysis resolved using scanning tunnelling microscopy. AB - The technique of scanning tunnelling microscopy has revolutionised our understanding of surface chemistry, due to its ability to image at the atomic and molecular scale, the very realm at which chemistry operates. This critical review focuses on its contribution to the resolution of various problems in heterogeneous catalysis, including surface structure, surface intermediates, active sites and spillover. In the article a number of images of surfaces are shown, many at atomic resolution, and the insights which these give into surface reactivity are invaluable. The article should be of interest to catalytic chemists, surface and materials scientists and those involved with nanotechnology/nanoscience. (129 references.)The graphical abstract shows the reaction between gas phase methanol and oxygen islands on Cu(110), courtesy of Philip Davies of Cardiff University. The added-row island is shown as silver coloured spheres (copper) and red (oxygen) on the copper surface. Methanol preferentially reacts with the terminal oxygen atoms in the island forming adsorbed methoxy and OH groups. Only the terminal oxygen atoms in the island are active sites for the reaction. PMID- 17721589 TI - Peptidomimetics via copper-catalyzed azide-alkyne cycloadditions. AB - This critical review concerns the impact of copper-mediated alkyne-azide cycloadditions on peptidomimetic studies. It discusses how this reaction has been used to insert triazoles into peptide chains, to link peptides to other functionalities (e.g. carbohydrates, polymers, and labels), and as a basis for evolution of less peptidic compounds as pharmaceutical leads. It will be of interest to those studying this click reaction, peptidomimetic secondary structure and function, and to medicinal chemists. PMID- 17721590 TI - Introduction to the special issue dedicated to David Phillips. PMID- 17721591 TI - Fluorescence characterisation of multiply-loaded anti-HER2 single chain Fv photosensitizer conjugates suitable for photodynamic therapy. AB - We report the synthesis, spectroscopic properties and intracellular imaging of recombinant antibody single chain fragment (scFv) conjugates with photosensitizers used for photodynamic therapy of cancer (PDT). Two widely studied photosensitizers have been selected: preclinical pyropheophorbide-a (PPa) and verteporfin (VP), which has been clinically approved for the treatment of acute macular degeneration (Visudyne). Pyropheophorbide-a and verteporfin have been conjugated to an anti-HER2 scFv containing on average ten photosensitizer molecules per scFv with a small contribution ( A GAS6 polymorphism and stroke. In order to further explore this association by considering GAS6 haplotypes and the main stroke subtypes, 457 patients with ischemic stroke, 199 with hemorrhagic stroke and 150 asymptomatic controls were genotyped for eight GAS6 polymorphisms and other genetic markers in the same genome region. Association was measured by logistic regression analysis. The THESIAS program was used to measure linkage disequilibrium and haplotype frequencies. In univariate analysis, the GAS6 c.834 + 7AA genotype was found associated with decreased risk for stroke (OR: 0.59; 95%CI: 0.37-0.93). After adjustment for vascular risk factors, association was maintained when stroke subtypes affecting the microvasculature such as lacunar stroke and deep haemorrhage, were grouped together (OR: 0.44; 95%CI: 0.21-0.90). Furthermore, haplotype analysis revealed that association was even stronger when the c.834 + 7A allele was present in a specific haplotype (CACA) of four GAS6 polymorphisms. From these results we conclude that the A allele of the GAS6 c.834 + 7G > A polymorphism and more specifically, the CACA haplotype, is less prevalent in patients with stroke, suggesting a protective role for stroke of this haplotype. PMID- 17721625 TI - Evaluation of antibodies to oxidized low-density lipoprotein and assessment of C reactive protein in acute coronary syndrome and stable coronary artery disease. AB - The aim was to measure the level of antibodies to oxidized LDL (oxLDL) and C reactive protein (CRP) in the serum of patients with acute coronary syndrome (ACS). The results were correlated with data obtained from patients with stable coronary artery disease (stable CAD) and healthy controls. Thirty-three patients with ACS and 62 stable CAD patients were enrolled in the study. Fifty healthy individuals served as controls. The evaluation of anti-oxLDL autoantibodies was performed by ELISA, while CRP levels were measured by turbidimetry. The level of antibodies to oxLDL was significantly higher in both groups of patients with ACS and stable CAD compared to controls. The comparison between the acute and stable groups showed that anti-oxLDL levels were higher in the acute group, but because of high SD, the difference was not significant. By performing group analysis, anti-oxLDL levels were found to be significantly higher in ACS patients with unstable clinical state (circulatory insufficiency, malignant arrhythmias, recurring ischemic pain, need for urgent coronary intervention and death). CRP level in patients with ACS was significantly higher than in those with stable CAD. A positive correlation was found between anti-oxLDL antibodies and CRP levels both in patients with ACS and stable CAD. The association between the two biomarkers was stronger in the ACS group. In conclusion, our findings support the notion that the presence of antibodies to oxLDL, a plaque-specific antigen, plays a major role as a predictor of complicated manifestations of ACS. PMID- 17721626 TI - Prothrombotic markers and early spontaneous recanalization in ST-segment elevation myocardial infarction. AB - We tested the hypothesis that selected prothrombotic biomarkers might be associated with early spontaneous coronary recanalization in patients with ST segment elevation acute myocardial infarction (STEMI). We prospectively enrolled 123 patients with STEMI including 53 patients with spontaneous coronary recanalization (cases) and 70 patients with persistent occlusion (controls) at the time of emergent coronary angiography and before angioplasty. All had received aspirin and heparin. Blood samples were collected immediately before angioplasty to measure soluble P-selectin, circulating microparticles originating from platelets (PMPs), granulocytes (GMPs), endothelial cells (EMPs); tissue factor-associated MP (TF-MP); soluble platelet glycoprotein V (sGPV) and prothrombin F1 + 2; tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1) and plasmin-antiplasmin (PAP). A sub-group of 70 patients (35 cases, 35 controls) was available for flow cytometry analysis of platelet P selectin and activated GPIIb-IIIa. Baseline clinical characteristics did not differ between groups except for more frequent hypertension and dyslipidemia in controls. Platelet activation markers and PMP did not differ between the two groups. Controls had higher numbers of EMPs and GMPs compared to cases, but the difference was no longer significant when corrected for risk factors. Controls differed from cases by higher plasma levels of sGPV [64 (47-84) ng/ml vs. 53 (44 63) ng/ml] and PAP [114(65-225) ng/ml vs. 88 (51-147) ng/ml]. The difference persisted after adjustment for risks factors (p = 0.031 and 0.037, respectively). Persistent occlusion of the infarct related artery is associated with some markers related to higher thrombin (sGPV) and plasmin (PAP) production but is not associated with markers of platelet activation. PMID- 17721627 TI - Presence of NGAL/MMP-9 complexes in human abdominal aortic aneurysms. AB - It has been suggested that the intraluminal thrombus of abdominal aortic aneurysms (AAAs) predisposes for AAA enlargement and rupture. The growth of the AAA is dependent on proteolytic degradation of elastin. Here, we analysed whether the neutrophil gelatinase-associated lipocalin (NGAL) is expressed within the thrombus and the aneurysm wall. NGAL can bind to metalloproteinase-9 (MMP-9) and inhibit its degradation, thereby preserving enzymatic activity. Biopsies were obtained from thrombus-free and thrombus-covered aneurysm wall and the intraluminal thrombus from patients undergoing elective surgery for AAA. Immunohistochemistry and real-time PCR were used to study NGAL and MMP-9 expression. Immunoprecipitation, gel zymography, Western blot and ELISA were used to detect and quantify NGAL/MMP-9 complexes. NGAL was detected in the thrombus, the interface between the thrombus and the underlying wall and in the wall itself. Double staining showed that neutrophils are the major source of NGAL expression. Immunoprecipitation of MMP-9 with antibody against NGAL showed that complexes of NGAL and active MMP-9 were present in thrombus, the interface fluid and the aneurysm wall. Western blot analyses using non-reducing conditions and gel zymography demonstrated that high-molecular-weight complexes of NGAL/MMP-9 were present within the different regions. The concentration of the NGAL/MMP-9 complex was highest in the luminal part of the thrombus. In conclusion, NGAL in complex with activated MMP-9 is present in AAA wall and thrombus. Neutrophil derived NGAL could enhance the proteolytic activity associated with AAA, but the importance of this mechanism for aneurysm growth remains to be shown. PMID- 17721628 TI - Effect of low-molecular-weight heparin on survival in patients with advanced pancreatic adenocarcinoma. AB - This retrospective analysis aimed to identify whether low-molecular-weight heparins (LMWH) might improve survival in patients receiving chemotherapeutic treatment for advanced pancreatic adenocarcinoma. Two hundred forty-three patients who had received chemotherapy for advanced pancreatic adenocarcinoma were identified from a prospectively maintained database. Of these, 30 patients had to be excluded from analysis due to insufficient documentation. Of the remaining 213 patients 94 patients had been treated with LMWH, whereas 119 patients served as controls. Outcome was assessed in relation to overall survival, which was calculated from the date of initiation of chemotherapy to the date of death. There was no significant difference (hazard ratio, 0.8; 95% confidence interval (CI), 0.6 to 1.1; P = 0,2) between the two groups in terms of overall survival. The median survival was 7.1 months (95% CI, 5.8-8.4 months) in the LMWH group and 5.9 months (95% CI, 5.1-6.7 months) in the non-LMWH group. A positive effect of LMWH was seen in patients with metastatic disease (hazard ratio for LMWH vs. non-LMWH, 0,6; 95% CI, 0,4 to 0,8; P = 0,006) in contrast to those without metastatic disease (hazard ratio for LMWH vs. non-LMWH, 1; 95% CI, 0.6 to 1.7; P = 0,96). The median survival of patients with metastatic disease was 6,6 months (95% CI, 5-8, 2 months) and 3.8 months (95% CI, 2.5-5.1 months) for the LMWH group and the non-LMWH group, respectively. In conclusion, we found for metastatic pancreatic adenocarcinoma a survival advantage for patients receiving LMWH. Nevertheless, our observations need confirmation by prospective randomized studies. PMID- 17721629 TI - VEGFR2 expressing circulating (progenitor) cell populations in volunteers and cancer patients. AB - Circulating cells of several lineages are thought to participate in angiogenesis and tumor growth. Experimental studies in tumor-bearing mice have pointed to the potential importance of VEGF-responding circulating (endothelial) progenitor cells in tumor growth. We have studied circulating CD31- and/or CD34-positive cell populations with a low to moderate VEGFR2 expression in human volunteers and cancer patients. We recognized four cell populations, which were further characterized by their content of major hematopoietic progenitor, monocytic, endothelial and platelet markers. After establishing the test-retest stability of the measurements in nine patients, we determined the frequencies of the various cell populations in a group of 20 volunteers and 14 cancer patients. Two populations were markedly increased in cancer patients. Small CD45(neg)/CD34(bright)/VEGFR2+ cells amounted to 12 and 64 cells/ml (P < 0.0001), respectively, and 246/ml and 578/ml VEGFR2+/CD45(bright) (/CD14+) monocytic cells were present in controls and cancer patients, respectively (P = 0.017). A third population of CD45(dim)/CD34(bright)/VEGFR2(low) cells amounted to 25 and 30 cells/ml (P = 0.38). Unexpectedly, a population of mainly anucleated CD45(low)/CD31(bright)/CD41(bright) cells was present in numbers of 9,076 and 16,697/ml (P = 0.04) in volunteers and cancer patients, which contained a VEGFR2(low) (compared to IgG isotype control) expressing population amounting to 1,142 and 1,642 cells/ml (P = 0.12). This fourth population probably reflects large platelets. The role of the herein identified VEGFR2+ circulating cell populations deserve further investigation in cancer patients treated with VEGF(R) targeted therapies. Quantification of such cell populations in the blood of tumor patients may be valuable to monitor the efficacy of anti-angiogenic treatment. PMID- 17721630 TI - Flow cytometric analysis of circulating platelet-monocyte aggregates in whole blood: methodological considerations. AB - Platelet-monocyte aggregates are increasingly being used to quantify platelet activation. The variables that influence platelet-monocyte aggregates have not been well defined. We sought to determine the effect of blood collection, handling and processing techniques on detected levels of platelet-monocyte aggregates using a flow cytometric assay. Whole blood was labelled with anti-CD14 PE and anti-CD42a-FITC. Thereafter, samples were fixed and red cells lysed. Analysis was performed with the flow cytometer initially triggering on light scatter and then on FL-2 to identify CD14-PE positive monocytes. Platelet monocyte aggregates were defined as monocytes positive for CD42a. The effect of collection, handling and processing techniques on this assay were assessed. Anticoagulation with heparin (20.1 +/- 2.0%), PPACK (16.8 +/- 1.9%), sodium citrate (12.3 +/- 1.6%) and EDTA (9.5 +/- 1.0%) resulted in markedly different levels of platelet-monocyte aggregation (P < 0.0001). Platelet-monocyte aggregation was higher in samples obtained from intravenous cannulae compared to those obtained by venepuncture (20.9 +/- 3.9% vs.13.8 +/- 2.4%, P = 0.03). For every 10 minutes of delay prior to processing platelet-monocyte aggregates increased by 2.8% (P = 0.0001) in PPACK anticoagulated blood and 1.7% (P = 0.01) in citrate anticoagulated blood. Erythrocyte lysis together with fixation does not affect platelet-monocyte aggregation. Platelet-monocyte aggregates remained stable over 24 hours when fixed and stored at 4 degrees C. Multiple handling and processing factors may affect platelet-monocyte aggregation. We recommend the measurement of platelet-monocyte aggregates on samples collected by direct venepuncture, using a direct thrombin inhibitor as the anticoagulant and minimising the time delay before sample fixation. PMID- 17721631 TI - The risk of venous and arterial thrombosis in hyperhomocysteinaemia is low and mainly depends on concomitant thrombophilic defects. AB - As homocysteine-lowering treatment has not reduced the risk of recurrent thrombosis in recent clinical trials, we hypothesized that mild hyperhomocysteinaemia is an epiphenomenon or associated with a low absolute risk of thrombosis. In this retrospective study, we enrolled 478 evaluable first degree relatives of consecutive patients with venous thrombosis or premature atherosclerosis, and hyperhomocysteinemia. Absolute risks of thrombosis and effects of concomitant thrombophilic defects were compared. Relative risks were adjusted for clustering in families, age, sex, and atherosclerotic risk factors, where appropriate. Annual incidence of venous thrombosis was 0.16% (95% confidence interval [CI], 0.08-0.30) in hyperhomocysteinemic relatives versus 0.11% (CI, 0.05-0.20) in normohomocysteinemic relatives; adjusted relative risk 1.6 (CI, 0.6-4.5). Annual incidences of arterial thrombosis were 0.34% (CI, 0.21 0.52) and 0.24% (CI, 0.15-0.37) in hyperhomocysteinemic and normohomocysteinemic relatives, respectively; adjusted relative risk 1.5 (CI, 0.6-3.5). Concomitance of multiple thrombophilic risk factors increased the risk of venous thrombosis in hyperhomocysteinemic relatives 20 fold, but a comparable effect was demonstrated in normohomocysteinemic relatives. We conclude that hyperhomocysteinaemia is associated with a low absolute risk of venous and arterial thrombosis. Concomitant thrombophilic defects are probably main determinants on the risk of venous thrombosis, rather than hyperhomocysteinaemia itself. PMID- 17721632 TI - Identification of a novel candidate splice site mutation (0874 + 1G > A) in a type 3 von Willebrand disease patient. PMID- 17721633 TI - Congenital hypodysfibrinogenaemia (Fibrinogen Des Moines) due to a gamma320Asp deletion at the Ca2+ binding site. PMID- 17721634 TI - Heparin-induced thrombocytopenia II-induced critical limb ischaemia treated with urokinase and argatroban. PMID- 17721635 TI - Retinal central artery occlusion in a young woman after ten days of a drospirenone-containing oral contraceptive (Yasmin). PMID- 17721636 TI - More on the Impact Factor and thrombosis and haemostasis journals: benefits and limitations. PMID- 17721637 TI - Persistence of phosphatidylserine exposure on activated platelets in vivo in rabbits. PMID- 17721638 TI - Plasminogen activator inhibitor-1 has a circadian rhythm in blind individuals. PMID- 17721639 TI - Effects of biphenyldimethyl-dicarboxylate administration alone or combined with silymarin in the CCL4 model of liver fibrosis in rats. AB - The effect of biphenyldimethyldicarboxylate (DDB), a synthetic compound, in use for the treatment of chronic hepatitis was studied on hepatic injury caused in rats by administration of carbon tetrachloride (CCl4). Starting at time of administration of the first dose of CCl4, rats received DDB at four dose levels (3, 15, 75 or 375 mg/kg), silymarin (22 mg/kg), a combination of DDB (75 mg/kg) and silymarin (22 mg/kg) or saline (control) once orally daily for 30 days. The administration of DDB in CCl4-treated rats at 75 or 375 mg/kg resulted in 61.2 76.2% decrease in alanine aminotransferase (ALT) and 46.9-60.8% decrease in aspartate aminotransferase (AST), respectively compared with the CCl4 control group. Silymarin treatment resulted in 34.6 and 30% decrease in ALT and AST, while DDB (75 mg/kg) combined with silymarin (22 mg/kg) resulted in 58.2 and 31% decrease in ALT and AST, respectively. Serum creatinine increased by 50% by DDB at 375 mg/kg. After treatment with DDB at 75 or 375 mg/kg or DDB combined with silymarin, the development of liver necrosis and fibrosis caused by CCl4 was markedly reduced, while after DDB combined with silymarin no DNA aneuploid cells could be observed. The decrease in glycogen and protein contents in hepatocytes caused by CCl4 was markedly prevented by co-treatment with DDB at 75 or 375 mg/kg or DDB combined with silymarin. It is concluded that in the model of hepatic injury caused by chronic administration of CCl4 in rats, the synthetic compound DDB, limits hepatocellular injury and exerts antifibrotic effect. Better improvement in protein, DNA, mucopolysaccharide content was seen after both DDB and silymarin compared to DDB alone. It is suggested, therefore, that DDB alone or in combination with silymarin might prove of benefit in the therapy of chronic liver disease. Monitoring of kidney functions in patients taking DDB is warranted. PMID- 17721640 TI - The efficacy of treatment of different intervention programs for patellofemoral pain syndrome--a single blinded randomized clinical trial. Pilot study. AB - Patello-femoral pain syndrome (PFPS) is a common knee joint disability. The integration of hip soft tissue regimens are not always emphasized, although current literature implies that there is a significant relationship between the two and there is a lack of randomized clinical trials to substantiate this relationship in clinical practice. A randomized controlled assessor blinded trial was designed to explore different rehabilitation programs related to PFPS. The study was conducted at RAZIEL institute of physical therapy, Netania, Israel with a total of 30 consecutive patients (mean age 35y), diagnosed with PFPS. All patients were randomly allocated into 3 groups. Group I conventional knee rehabilitation program. Included quadriceps strengthening and Trans Electric Neuromuscular Stimulation (TENS). Group II hip oriented rehabilitation program. included stretching, Hip external rotators strengthening and TENS. Group III a combination of the two above programs. Pain and function were documented on initial of the program and again 3 weeks later, on the completion. Pain was assessed by a numeric visual analogue scale (VAS); function was assessed by Patello-femoral joint evaluation scale (PFJES) (0-100 points). At end of trial, all groups showed significant improvements in VAS and PFJES (p<0.0001); these improvements did not vary significantly between the 3 groups. The conclusions were that the explored different rehabilitation programs showed a similar beneficial effect. PMID- 17721641 TI - Orexitropic signaling proteins in obese children. AB - Adipose tissue is not only the main organ for energy storage, but it also has endocrine properties, producing "adipokines" responsible for energy homeostasis, insulin sensitivity, and inflammation. Leptin, produced by adipocytes, is the key hormone in appetite regulation and suppression of orexigenic, hypothalamic neuropeptide Y (NPY). We wanted to establish and compare levels of leptin and NPY in different obesity types in childhood, and to investigate their correlations with auxological parameters. Twenty-one obese children (seven girls and 14 boys), divided into two groups, were compared with 14 controls. The mean age of the study group was 10.81 +/- 3.69 years and the mean puberty stage was 2.21. The mean body mass index (BMI) was 32.80 kg/m2 (range 23.30-47.02) and the mean overweight 30.73 kg (range 8.00-74.00). The mean leptin level was higher in boys and in the group with central obesity, but was not significant. Leptin/NPY ratio and leptin/BMI ratio was also higher in the central obesity group and there was a more significant difference compared with controls. We found significant correlation of the leptin level with body mass (BM), body mass excess (BME), and BMI (p < 0.05). The mean leptin level in obese children was very high (36.39 ng/ml). Leptin and NPY levels showed inverse values in two different obesity types. Results are suggestive for leptin resistance rather than leptin deficiency in our group of obese children. Orexitropic signaling proteins correlated significantly with auxological parameters. Determination of the leptin and NPY concentrations provided evidence that obesity represents disease with neuroendocrine dysfunction and high leptin/NPY ratio, which could be a useful marker for central obesity. PMID- 17721642 TI - Quantifying the impact of obesity category on major chronic diseases in Canada. AB - Adverse health effects differ with various levels of obesity, but limited national data existed previously for the Canadian population. We examined the associations of sociodemographic and behavioral factors with obesity levels in Canada, and measured the impact of each level on major chronic diseases. Data were extracted from the 2003 Canadian Community Health Survey. We grouped overweight/obese participants aged 18 years and over into four levels based on body mass index (BMI, kg/m2): overweight (25.0 C29.9), class I obesity (30.0 C34.9), class II obesity (35 C39.9), and class III obesity (extreme/clinical obesity, BMI > or = 40.0). We used logistic regression models to identify potential risk factors for the obesity levels and to estimate adjusted odds ratios (ORs) for major chronic diseases related to each level. We calculated population attributable risks (PARs) to help understand the impact of obesity levels on these chronic diseases. The overall prevalence of obesity was 16.2% in men and 14.6% in women, and the prevalence of obesity III was 1.0% in men and 1.4% in women. All levels of obesity increased with age, but then decreased in elderly participants. The prevalence of diabetes, hypertension, heart disease, arthritis, and asthma increased with increasing BMI level, and the highest values appeared in participants at the obesity III level. PAR was highest in the obesity III group for hypertension, followed by diabetes, and lowest for heart disease. When correlated with risk factors, fewer statistically significant ORs, comparing to the normal weight category, appeared for obesity II and III levels than for overweight and obesity I. ORs for the combination of low education level, infrequent exercise, and low household income rose significantly with BMI levels until the obesity II level, and in obesity III level, the OR remained at the same level as for obesity II, most significantly in women. These results suggest that the impact of obesity on Canadians inverted exclamation mark health should be studied and dealt with by obesity level. The greatest impact of clinical obesity was on hypertension and diabetes control in Canada. PMID- 17721643 TI - Homozygous missense mutation in the ECM1 gene in Chinese siblings with lipoid proteinosis. AB - Lipoid proteinosis is caused by loss-of-function mutations in the glycoprotein extracellular matrix protein 1 (ECM1). We report here mutation analysis of the ECM1 gene in a Chinese family with lipoid proteinosis. A 10-year-old boy presented with a hoarse voice, acneiform scars and yellow skin nodules, as well as beaded eyelid papules and a thickened sublingual frenulum. Skin biopsy showed widespread deposition of hyaline material in the dermis and thickened basement membrane. His elder sister had the same clinical manifestations. The coding region of ECM1 was amplified and sequenced and both affected siblings were shown to have a novel homozygous single nucleotide substitution, c.658T>G, in exon 6, which converts cysteine to glycine, designated p.C220G. Both parents were heterozygous for this mutation which was not detected in 100 control chromosomes. Missense mutations in the ECM1 gene are an unusual finding in lipoid proteinosis, but this case adds to the spectrum of disease-associated mutations in this rare genodermatosis. PMID- 17721644 TI - Serotonergic mechanisms in human allergic contact dermatitis. AB - Expression of serotonin (5-hydroxytryptamine; 5-HT), 5-HT receptors 1A (5-HT1AR) and 2A, and serotonin transporter protein (SERT) was studied in positive epicutaneous reactions to nickel sulphate in nickel-allergic patients, at 72 h post-challenge with the antigen. In addition, the effects of 5-HT2AR agonist 2,5 dimethoxy-4-iodoamphetamine (DOI), and the selective serotonin reuptake inhibitors (SSRIs) citalopram and fluoxetine, were tested on nickel-stimulated peripheral blood mononuclear cells from nickel-allergic patients, regarding their proliferation and interleukin (IL)-2 production, as well as the effect of these SSRIs on a murine Langerhans' cell-like line (XS52), regarding its IL-1beta production. Serotonin-positive platelets were increased in the inflamed skin compared with control skin. A decrease (p <0.01) in 5-HT1AR-positive mononuclear cells was evident in the eczematous skin compared with control skin, whereas 5 HT2AR- and SERT-positive cells were increased (p <0.001 for both) in the eczematous skin. Treatment of nickel-stimulated peripheral blood mononuclear cells with 5x10(-5) mol/l of DOI inhibited (p <0.01) the proliferation of nickel stimulated peripheral blood mononuclear cells, while no effect was found regarding IL-2 production. Citalopram at 10(-6) mol/l tended to inhibit the production of IL-1beta by the XS52 cell line. These results indicate the implication of the serotonergic system in the contact allergic reaction. PMID- 17721645 TI - Videoconferencing journal club for dermatology residency training: an attitude study. AB - The use of videoconferencing as a teaching modality in dermatology is not widespread. The objectives of this study were to introduce the videoconferencing format to dermatology journal clubs and to determine its effects on the training and satisfaction of house officers (residents). Ten dermatology house officers participated in this study. They were being trained at three university hospitals in rotation. A videoconferencing facility maintained by the hospitals for remote conferencing was used. After completing a 1-year journal club programme, house officers were asked about their satisfaction levels on a 5-point Likert scale using a questionnaire. Videoconferencing meant that the house officers and attending physicians from sister hospitals remained at their own hospitals, thus saving much time. Using videoconferencing the journal club could be held more frequently and more articles could be studied. In general the participants' satisfaction with the videoconferencing journal club was high. The adoption of videoconferencing produced promising results, increasing the efficiency of house officer training. PMID- 17721646 TI - Porphyria cutanea tarda: effects and risk factors for hepatotoxicity from high dose chloroquine treatment. AB - High-dose chloroquine therapy for porphyria cutanea tarda is rarely used now because of its hepatic side-effects. The mechanisms of the effects and side effects are poorly understood. We describe here effects, side-effects and long term follow-up in 57 patients with a first-time diagnosis of porphyria cutanea tarda treated with 1-3 phlebotomies followed by 250 mg chloroquine phosphate daily for 7 days. A hepatotoxic reaction with high serum aminotransferases occurred in almost all patients. Within 3 months, clinical remission was obtained in all patients, and biochemical remission in almost all patients. Relapse occurred in 27 patients after 0.5-12 years. Subjective side-effects occurred more frequently in women, who also had higher maximum ALAT, ferritin and uroporphyrin values during treatment. Both subjective side-effects and ALAT during treatment correlated with pre-treatment uroporphyrin excretion and maximum uroporphyrin during treatment, but not with markers of hereditary haemochromatosis. PMID- 17721647 TI - Long-term treatment with 0.1% tacrolimus ointment in adults with atopic dermatitis: results of a two-year, multicentre, non-comparative study. AB - Atopic dermatitis often requires long-term treatment. This European, multicentre, non-comparative, 24-month, follow-up study investigated the efficacy and safety of 0.1% tacrolimus ointment applied to adults with atopic dermatitis. Patients (n=672) applied a thin layer of 0.1% tacrolimus ointment twice daily for 3 weeks to all affected body areas. After 3 weeks, ointment was applied once daily. Clinical improvement became apparent after 2 weeks of treatment and 65.5% of patients had a rating of clearance, excellent or marked improvement by month 3. Skin burning (31.7%) was the most common causally-related adverse event, followed by pruritus (11.3%) folliculitis (6.4%), alcohol intolerance (5.7%), herpes simplex (5.7%), skin infection (4.6%), skin erythema (3.3%) and hyperaesthesia (2.4%). The most commonly reported infections were flu syndrome (12.9%), skin infection (9.8%), folliculitis (7.4%) and herpes simplex (7.0%). Long-term treatment up to 24 months with 0.1% tacrolimus ointment is safe and efficacious in adults with atopic dermatitis. PMID- 17721648 TI - Narrowband UVB and PUVA in the treatment of mycosis fungoides: a retrospective study. AB - Psoralen plus ultraviolet A (PUVA) is widely used as first-line therapy for treatment of mycosis fungoides. Narrowband ultraviolet B (NB-UVB) has also been shown to be effective for treatment of early mycosis fungoides. The aim of this retrospective study was to analyse the response to treatment and relapse-free interval for PUVA and NB-UVB therapies in mycosis fungoides. Forty patients were treated with PUVA or NB-UVB between 1980 and 2003. All patients had failed to respond to topical therapy or were unwilling to use it. PUVA therapy was used between 1980 and 1997. Thereafter, the choice between PUVA (twice a week) and NB UVB therapy (three times a week) depended on stage and extent of the disease as well as on how far patients had to travel). Twelve patients (stage IA-IIB) were treated with NB-UVB and 28 patients (stage IA-IVA) with PUVA. No maintenance therapy was given. Six patients (50%) had a complete response, 4 (33%) had a partial response and 2 (16%) had a failed response to NB-UVB but had stable disease. PUVA led to a complete response in 18 (64%), a partial response in 6 (21%) and a failed response in 4 (14%) patients. The median relapse-free interval was 11.5 months in the NB-UVB treated group and 10 months in the PUVA group. The majority of the patients (79%) had stage IA and IB disease. Of these, 6 of 10 (60%) in the NB-UVB group and 13/21 (62%) in the PUVA group had a complete response to treatment. These results show that PUVA and NB-UVB are effective treatments for early mycosis fungoides. PMID- 17721649 TI - Early disseminated borreliosis with multiple erythema migrans and elevated liver enzymes: case report and literature review. AB - A 69-year-old man presented with multiple livid maculae and infiltrated urticarial plaques, as well as elevated liver enzymes. Based on typical clinical picture, histopathology and positive PCR from a skin biopsy, we diagnosed an early disseminated infection with Borrelia afzelii presenting with multiple erythema migrans (erythemata migrantia) and a subclinical hepatitis. During antibiotic treatment with intravenous ceftriaxone, the maculae and plaques vanished almost completely and the liver enzymes decreased within 14 days. Dermatologists should keep in mind that early disseminated borreliosis can present with multiple erythema migrans and hepatitis. PMID- 17721650 TI - Ulcerous lesions disclosing cutaneous infection with Fusarium solani. AB - Fusarium spp. are emergent opportunistic moulds capable of producing life threatening diseases, usually in immunocompromised hosts. When they infect immunocompetent patients, they usually cause localized diseases. We describe here a case of cutaneous fusariosis in a patient with a medical history of diabetes mellitus and non-Hodgkin's lymphoma who presented with two painful lesions on her left leg. The diagnosis was made on the basis of histopathological findings and skin biopsy culture. The lesions resolved after treatment with oral itraconazole. Cutaneous fusariosis manifests clinically as lesions that can be grouped into a few clinical patterns, and should always be considered in the differential diagnosis of necrotic cutaneous lesions. PMID- 17721651 TI - Concomitant Sweet's syndrome and relapsing polychondritis. PMID- 17721652 TI - Diagnosis and treatment of post-Caesarean scar endometriosis. PMID- 17721653 TI - Sporotrichosis following mesotherapy for arthrosis. PMID- 17721654 TI - A case of malignant melanoma arising from an acquired agminated melanocytic naevus. PMID- 17721655 TI - Bullous lesions at polyethylene glycol interferon-alpha-2a inoculation site in a hepatitis C virus-infected subject. PMID- 17721657 TI - Psoriasiform eruption associated with graft-versus-host disease. PMID- 17721656 TI - Clearance of recurrent, classical Kaposi's sarcoma using multiple paclitaxel treatments. PMID- 17721658 TI - A case of complex regional pain syndrome: an underdiagnosed condition in dermatology. PMID- 17721659 TI - Widespread vitiligo after erythroderma caused by nevirapine in a patient with AIDS. PMID- 17721660 TI - Primary cutaneous cryptococcosis presenting as a whitlow. PMID- 17721661 TI - Metastasizing squamous cell carcinomas in a patient treated with extracorporeal photopheresis for cutaneous T-cell lymphoma. PMID- 17721662 TI - A rapidly growing squamous cell carcinoma or keratoacanthoma or both? PMID- 17721663 TI - Combination of acitretin and oral calcitriol for treatment of plaque-type psoriasis. PMID- 17721664 TI - Intramuscular triamcinolone acetonide for lupus miliaris disseminatus faciei. PMID- 17721665 TI - Cutaneous pseudolymphoma following administration of lornoxicam. PMID- 17721667 TI - Idealized cultural beliefs about gender: implications for mental health. AB - BACKGROUND: In this paper, we examined the relationship between culture-specific ideals (chastity, masculinity, caste beliefs) and self-esteem, shame and depression using an idealized cultural model proposed by Mahalingam (2006, In: Mahalingam R (ed) Cultural psychology of immigrants. Lawrence Erlbaum, Mahwah, NJ, pp 1-14). METHODS: Participants were from communities with a history of extreme male-biased sex ratios in Tamilnadu, India (N = 785). RESULTS: We hypothesized a dual-process model of self-appraisals suggesting that achieving idealized cultural identities would increase both self-esteem and shame, with the latter leading to depression, even after controlling for key covariates. We tested this using structural equation modeling. The proposed idealized cultural identities model had an excellent fit (CFI = 0.99); the effect of idealized identities on self-esteem, shame and depression differed by gender. CONCLUSIONS: Idealized beliefs about gender relate to psychological well-being in gender specific ways in extreme son preference communities. We discuss implications of these findings for future research and community-based interventions. PMID- 17721669 TI - Physical activity, dietary habits and Coronary Heart Disease risk factor knowledge amongst people with severe mental illness: a cross sectional comparative study in primary care. AB - BACKGROUND: Evidence regarding Coronary Heart Disease (CHD) related lifestyle in people with severe mental illnesses (SMI) such as schizophrenia is sparse. We aimed to quantify adverse CHD knowledge, diet and exercise in a representative primary care sample, and to determine whether socio-economic deprivation explained any findings. METHOD: We compared CHD lifestyle and CHD knowledge in 74 people with SMI and 148 without from seven general practices. We measured CHD knowledge, dietary fibre, fats and exercise using validated instruments and adjusted for socio-economic status. RESULTS: Fewer people with SMI had higher CHD knowledge: OR 0.49 (95% CI: 0.27-0.88), higher total exercise scores 0.49 (0.27 0.86), higher fibre 0.46 (0.26-0.82) or lower saturated fat diets 0.53 (0.30 0.94). These results were stable irrespective of antipsychotic medication, socio economic status or type of statistical analysis. CONCLUSION: High fat, low fibre diets, lack of exercise and smoking are the likely causes of the majority of CHD in this high-risk group, irrespective of medication and socio-economic deprivation. This lifestyle and particularly the lower CHD knowledge provides a theoretical focus for more comprehensive preventative CHD interventions in SMI. PMID- 17721668 TI - Childhood trauma history and dissociative experiences among Turkish men diagnosed with antisocial personality disorder. AB - OBJECTIVE: This study investigated the association between antisocial personality disorder (APD), childhood trauma history, and dissociative symptoms in a sample of Turkish recruits. METHODS: A total of 579 male patients diagnosed with APD were examined in a military hospital setting. An age and gender matched control group of 599 normal persons with no known medical or psychiatric disorder were also chosen among military personnel. The subjects were evaluated with an assessment battery using a semi-structured interview for socio-demographic characteristics, APD section of SCID-II, an adapted version of the Structured Trauma Interview, and Dissociative Experiences Scale. RESULTS: Childhood sexual abuse, physical abuse, neglect, and early separation from parents were significantly more common among antisocial subjects than among controls. APD group reported significantly more dissociative symptoms and 50.4% of them reported pathological level of dissociation. Overwhelming childhood experiences of all four types were significant predictor of the APD diagnosis. Analyses also showed that childhood traumatic events and comorbid psychopathological features relevant to antisocial personality were significantly associated with pathological level of dissociation. CONCLUSION: These results revealed the importance of inquiring about patient's history of childhood traumatization and dissociative experiences when diagnosed with APD. PMID- 17721670 TI - Doctors' attitude towards people with mental illness in Western Nigeria. AB - INTRODUCTION: It had been suggested that those more knowledgeable about mental illness are less likely to endorse negative or stigmatizing attitudes. This study aimed to evaluate the attitude of doctors in Nigeria towards the mentally ill. METHODS: Medical doctors (n = 312) from eight selected health institutions in Nigeria completed various questionnaires on knowledge and attitude towards people with mental illness. RESULTS: Beliefs in supernatural causes were prevalent. The mentally ill were perceived as dangerous and their prognosis perceived as poor. High social distance was found amongst 64.1% and the associated factors include not having a family member/friend with mental illness (OR 7.12, 95% CI 3.71 13.65), age less than 45 years (OR 2.33, 95% CI 1.23-4.40), less than 10 years of clinical experience (OR 6.75, 95% CI 3.86-11.82) and female sex (OR 4.98, 95% CI 2.70-9.18). CONCLUSION: Culturally enshrined beliefs about mental illness were prevalent among Nigerian doctors. A review of medical curriculum is needed and the present anti-stigma campaigns should start from the doctors. PMID- 17721671 TI - Patients' perspectives on what works in psychoeducational groups for schizophrenia: a qualitative study. AB - BACKGROUND: Psychoeducational groups are a common component of interventions in schizophrenia. AIMS: To explore patients' views about wanted and unwanted effects of group psychoeducation. METHOD: Subjective feedback of 103 participants of a psychoeducational intervention as well as data from two specific focus groups-one with "enthusiastic" and one with "critical" participants-were analyzed by means of qualitative content analysis. RESULTS: Participants emphasized the importance of information received and of exchanging information with others suffering from the same disorder. Positive effects on coping, activation and social interaction were reported. Perceived overemphasis on illness related information produced defensive reactions, whereas the integration of quality of life topics was appreciated. A pleasant group atmosphere and clinical stability were suggested as important determinants of success. CONCLUSIONS: Qualitative analyzses of participants' views help to understand the potentials of a psychoeducational intervention in schizophrenia. PMID- 17721674 TI - Prediction of mutations engineered by randomness in H5N1 neuraminidases from influenza A virus. AB - In this proof-of-concept study, we attempt to determine whether the cause mutation relationship defined by randomness is protein dependent by predicting mutations in H5N1 neuraminidases from influenza A virus, because we have recently conducted several concept-initiated studies on the prediction of mutations in hemagglutinins from influenza A virus. In our concept-initiated studies, we defined the randomness as a cause for mutation, upon which we built a cause mutation relationship, which is then switched into the classification problem because the occurrence and non-occurrence of mutations can be classified as unity and zero. Thereafter, we used the logistic regression and neural network to solve this classification problem to predict the mutation positions in hemagglutinins, and then used the amino acid mutating probability to predict the would-be-mutated amino acids. As the previous results were promising, we extend this approach to other proteins, such as H5N1 neuraminidase in this study, and further address various issues raised during the development of this approach. The result of this study confirms that we can use this cause-mutation relationship to predict the mutations in H5N1 neuraminidases. PMID- 17721672 TI - Dynamic behavior of an intrinsically unstructured linker domain is conserved in the face of negligible amino acid sequence conservation. AB - Proteins or regions of proteins that do not form compact globular structures are classified as intrinsically unstructured proteins (IUPs). IUPs are common in nature and have essential molecular functions, but even a limited understanding of the evolution of their dynamic behavior is lacking. The primary objective of this work was to test the evolutionary conservation of dynamic behavior for a particular class of IUPs that form intrinsically unstructured linker domains (IULD) that tether flanking folded domains. This objective was accomplished by measuring the backbone flexibility of several IULD homologues using nuclear magnetic resonance (NMR) spectroscopy. The backbone flexibility of five IULDs, representing three kingdoms, was measured and analyzed. Two IULDs from animals, one IULD from fungi, and two IULDs from plants showed similar levels of backbone flexibility that were consistent with the absence of a compact globular structure. In contrast, the amino acid sequences of the IULDs from these three taxa showed no significant similarity. To investigate how the dynamic behavior of the IULDs could be conserved in the absence of detectable sequence conservation, evolutionary rate studies were performed on a set of nine mammalian IULDs. The results of this analysis showed that many sites in the IULD are evolving neutrally, suggesting that dynamic behavior can be maintained in the absence of natural selection. This work represents the first experimental test of the evolutionary conservation of dynamic behavior and demonstrates that amino acid sequence conservation is not required for the conservation of dynamic behavior and presumably molecular function. PMID- 17721673 TI - Analysis of organochlorine pesticides in coral (Porites evermanni) samples using accelerated solvent extraction and gas chromatography/ion trap mass spectrometry. AB - A gas chromatography/ion trap mass spectrometry method was developed for analysis of organochlorine pesticides (OCPs) in coral samples, which were extracted with accelerated solvent extraction (ASE) and cleaned up on a sulfuric acid-modified silica gel column. The optimal ASE conditions were found to be 100 degrees C and 2000 psi, with a mixture of acetone and methylene chloride (1:1, v/v). The target analytes include hexachlorocyclohexanes (HCHs, specifically, alpha-, beta-, gamma , and delta-HCH isomers), heptachlor, and hexachlorobenzene (HCB), o,p'-, p,p' dichlorodiphenyltrichloroethane (o,p'-, p,p'-DDT), o,p'-, p,p'-dichlorodiphenyl dichloroethylene (o,p'-, p,p'-DDE), and o,p'-, p,p' dichlorodiphenyldichloroethane (o,p'-, p,p'-DDD). Standard sand samples were used as an alternative matrix spiked with OCP standards to determine the method precision and accuracy. Average recoveries of OCPs ranged from 82% to 102%, with relative standard deviations (RSDs) of 3%-6%, at a level of 10 ng/g and from 50% to 68%, with RSDs of 13%-19% at a level of 2 ng/g. The developed method was applied for analysis of OCPs in coral samples collected from Tern Island and Bikini Atoll in the Pacific Ocean. The concentrations of HCB were 7-26 pg/g dry weight in the samples from Bikini Atoll and 3-45 pg/g in those from Tern Island, and heptachlor concentrations were 208-2200 and 44-104 pg/g in the coral samples from Bikini Atoll and Tern Island, respectively. (summation operator)HCH (sum of alpha-, beta-, gamma-, and delta-HCH) were 8-82 pg/g in Bikini Atoll coral and 86 629 pg/g in Tern island coral, and (summation operator)DDT (sum of o,p'-, p,p' DDD, o,p'-, p,p'-DDE, and o,p'- p,p'-DDT) were 80-212 pg/g in Bikini Atoll coral and 593-3165 pg/g in Tern Island coral. The results suggest that coral is a viable indicator species for pollution monitoring, which pollutants and their concentrations may be related to dated carbonate layers. PMID- 17721675 TI - Gas chromatographic analysis of amino acid enantiomers in Carbetocin peptide hydrolysates after fast derivatization with pentafluoropropyl chloroformate. AB - A novel sample preparation protocol for gas chromatographic (GC) analysis of amino acid enantiomers in peptides was developed. It comprises traditional acid hydrolysis, a novel treatment of the analytes with a fluoroalkyl chloroformate and GC/FID separation of enantiomers on a chiral capillary column. The major improvements consist in that the derivatization step proceeds in organic-aqueous media within seconds and the amino acid derivatives are volatile enough to suit the temperature range of the chiral Chirasil-Val capillary column. The approach was found beneficial for chiral analysis of pharmaceutically important Carbetocin peptide. PMID- 17721676 TI - Neutrophil fatty acid composition: effect of a single session of exercise and glutamine supplementation. AB - The fatty acid composition of immune cells appears to contribute to variations of cell function. The independent and combined effects of a single session of exercise (SSE) and glutamine supplementation (GS) on neutrophil fatty acid composition were investigated. Compared to control (no treatment given--i.e. neither SSE or GS), single session of exercise decreased myristic, palmitic and eicosapentaenoic (EPA) acids, and increased lauric, oleic, linoleic, arachidonic (AA) and docosahexaenoic (DHA) acids whereas glutamine supplementation combined with SSE (GS+SSE) increased oleic acid. Polyunsaturated/saturated fatty acid ratio and Unsaturation index were higher in neutrophils from the SSE and GS groups as compared with control. These findings support the proposition that SSE and GS may modulate neutrophil function through alterations in fatty acid composition. PMID- 17721677 TI - Gastric femoral hernia in a male cadaver with gastroptosis: case report and review of the literature. AB - The shape and the position of the stomach and its anatomic relations to the round viscera vary from individual to individual, but they also vary in the same subject depending on many factors. The downward displacement of the stomach is called gastroptosis. In the literature, there are only five case reports where the stomach constituted the content of a femoral hernia. The current study presents a case of a gastric femoral hernia in a cadaver along with a review of the relevant literature. During routine dissection of a 67-year-old male cadaver with a very large stomach and gastroptosis, a femoral hernia containing a part of the great curvature of the stomach was found. The length of the hernia sac was 5 cm, and its width was 3.5 cm. There was a disposition of the intestinal coils to the posterior wall and the lesser pelvis. The cadaver's former medical history and skin observation before dissection excluded any previous abdominal surgery. This is the second case of stomach herniation through the femoral ring in a male subject ever reported. The symptoms in this pathology vary from complete absence to symptoms due to high stenosis of the digestive tract, stomach strangulation and stomach wall necrosis. PMID- 17721678 TI - Chimpanzee deaths at Mahale caused by a flu-like disease. AB - A flu-like disease spread among chimpanzees (Pan troglodytes schweinfurthii) of the M group at Mahale Mountains National Park, Tanzania, from June to July 2006. This epizootic or epidemic killed up to 12 chimpanzees. The obvious evidence of their deaths came from finding the bodies of three infants who had previously shown some symptoms of the disease. At least one of these infants died of pneumonia. In addition, nine chimpanzees were missing after the outbreak. These individuals were assumed to have been killed by this epizootic because most of them had contact with the infected individuals on the last days they were observed. We also found two dead bodies during this period, which were thought to be those of two missing individuals. We confirmed 23 (35.4%) of 65 individuals of the M group showed some symptoms of the disease, although most of them (20/23) did not die. More than half of them (14/23) had kin showing symptoms. Since this epizootic may have been caused by contact with humans, it will be necessary to establish and follow appropriate protocols for researchers, tourists, and park staff to observe chimpanzees, and to explore the mechanism of disease transmission from humans to chimpanzees and among chimpanzees. PMID- 17721679 TI - Antibiotic prevention of infective endocarditis due to oral procedures: myth, magic, or science? AB - Infective endocarditis (IE) can be induced by bacteremia attributable to dental procedures. To prevent this disease, prophylactic administration of antimicrobials prior to dental procedures has been recommended in several countries. However, no prospective study has proved its efficacy in a clinical setting. Recent recommendations from the American Heart Association (AHA) strongly suggested that dental work is not an important cause of IE; therefore, prophylactic use of antibiotics is of no use in most cases. Prevention of IE may be essential but its pathology and epidemiology remain unclear in various aspects. This article reviews the theoretical background of IE prophylaxis, and discusses how we should proceed when patients with a known cardiac disorder visit the dental clinic. The discussion includes antibiotics usage, daily maintenance procedures, and a possible new strategy with the use of antibacterial substances. PMID- 17721680 TI - Evaluation of diagnostic methods for Candida albicans translocation in a mouse model: seminested polymerase chain reaction, blood culture, and serological assays. AB - For the rapid diagnosis of systemic Candida infection, we compared the performance of an established seminested polymerase chain reaction (snPCR), serological tests for (1 --> 3)-beta-D-glucan assay and Candida mannan antigen assay, and blood culture in our murine model for Candida albicans translocation. In this mouse model, C. albicans disseminated to the liver from the intestine after day 6.5; the snPCR and blood culture results became positive from days 8 to 8.5 in about 60% of infected mice with culture-proven translocation, and in 100% on day 9. Both (1 --> 3)-beta-D-glucan and Candida mannan antigen were elevated in the serum as early as day 6.5 of infection, though they did not identify Candida species. Because the established snPCR can differentiate four clinically important Candida species and conventional microbiological methods require at least 48 h to identify Candida species in blood samples, the snPCR assay is advantageous for rapidly identifying Candida species in the blood. Therefore, the combination of the serological assays and the snPCR seems to be valuable for the early diagnosis of systemic C. albicans infection. PMID- 17721681 TI - Utility of a rapid diagnosis kit for Mycoplasma pneumoniae pneumonia in children, and the antimicrobial susceptibility of the isolates. AB - We evaluated a kit for the rapid diagnosis of Mycoplasma pneumoniae infection and investigated the antimicrobial susceptibility of the isolates. A total of 194 otherwise healthy children, aged 0.3-14.9 years, were diagnosed as having pneumonia by chest X-ray findings between December 2003 and November 2004, and were admitted to Showa Hospital. Isolation of M. pneumoniae was attempted from a throat swab obtained on admission, and the complement fixation titer was measured in paired serum samples obtained at admission and at the convalescent stage. We also used a rapid diagnosis kit (ImmunoCard Mycoplasma) for the detection of specific immunoglobulin M antibody in paired sera. Pneumonia due to M. pneumoniae was defined by isolation of this microorganism, or by seroconversion, or a >or=4 fold increase in the antibody titer. Using each isolate, we determined the minimum inhibitory concentrations for five antimicrobial agents by the broth dilution method. M. pneumoniae pneumonia was diagnosed in 45 children (23.2%). The ImmunoCard had a sensitivity of 31.8% using admission serum and 88.6% using paired sera, while the specificity was 78.1% and 70.5%, respectively. M. pneumoniae was isolated from 14 of the 45 patients (31.1%). The 50%/90% minimum inhibitory concentration (microg/ml) of erythromycin, clarithromycin, azithromycin, minocycline, and levofloxacin was 0.006/0.012, or=2.25 mg/kg/day). Micafungin produced an excellent 30 day clinical response in patients with candidemia, including Candida parapsilosis; the overall 30-day clinical response was 86%. The administration of higher doses of micafungin accelerated the clinical response and duration until the clinical response in group II was significantly shorter than that in group I (P = 0.021). However, no significant differences were observed in the 30-day mortality attributable to the fungal infection between the two groups. Considering these results, we recommend the administration of 2.25 mg/kg/day or more of micafungin in the initial treatment of patients with candidemia. PMID- 17721684 TI - High prevalence of erythromycin resistance and macrolide-resistance genes, mefA and ermB, in Streptococcus pneumoniae isolates from the upper respiratory tracts of children in the Sapporo district, Japan. AB - Our previous study demonstrated that the frequency of penicillin-resistant Streptococcus pneumoniae (PRSP) was lower in our district than in districts in other Japanese studies. In this study, we investigated the prevalence of erythromycin resistance. The susceptibility to erythromycin and the distribution of the macrolide-resistance genes, mefA and ermB, were examined in S. pneumoniae isolates from the upper respiratory tracts of children in four cities in the Sapporo district, Hokkaido prefecture, Japan. Of the 156 isolates, 27 (17.3%) were erythromycin-sensitive, 6 (3.9%) were erythromycin-intermediately resistant, and 123 (78.9%) were erythromycin-resistant. Fifty-nine (37.8%) had the mefA gene, 89 (57.1%) had the ermB gene, and 129 (82.7%) had the mefA and/or the ermB gene. The ermB-positive isolates tended to show high resistance to erythromycin. Erythromycin-resistant isolates and the macrolide-resistance genes were often present in infants or younger children. The frequency of erythromycin-resistant isolates in the four cities was very high, ranging from 76.3% to 83. 3%, as high as the national average. Although erythromycin-resistant isolates generally tend to show cross-resistance to penicillin, the frequency of PRSP was very low in this study, as compared with other Japanese studies. Erythromycin resistance was frequently recognized not only in PRSP but also in penicillin-sensitive S. pneumoniae (PSSP) as well. In Japan, erythromycin resistance may have already become widespread, even in local areas where penicillin resistance is not especially prevalent. PMID- 17721685 TI - Clinical and bacteriological evaluation of the efficacy of piperacillin in children with pneumonia. AB - We aimed to prospectively evaluate the clinical and bacteriological effects of piperacillin in children with pneumonia. Twenty-eight patients (6 months to 5 years of age) with pneumonia were treated with piperacillin. In the same period, 95 strains of Haemophilus influenzae and 41 strains of Streptococcus pneumoniae were isolated in our department and the minimum inhibitory concentration (MIC) of piperacillin was determined. The clinical efficacy of piperacillin was excellent in 4 cases, good in 23, and fair in 1; the response rate was 96.4% (27/28). Among the isolates from our department, there were 4 strains (9.8%) of penicillin susceptible S. pneumoniae (PSSP), 32 strains (78.0%) of penicillin-intermediate resistant S. pneumoniae (PISP), and 5 strains (12.2%) of penicillin-resistant S. pneumoniae (PRSP). Against S. pneumoniae, the MIC50 and MIC90 for piperacillin were 0.5 microg/ml and 2 microg/ml, respectively. Panipenem showed the best results, followed by piperacillin, ampicillin, and flomoxef. Among the isolates from our department, there were 51 strains (53.7%) of beta-lactamase-negative ampicillin-susceptible H. influenzae, 42 strains (44.2%) of beta-lactamase negative ampicillin-resistant H. influenzae, 1 strain (1.1%) of beta-lactamase positive ampicillin-resistant H. influenzae, and 1 strain (1.1%) of beta lactamase-positive amoxicillin-clavulanic acid-resistant H. influenzae. The MIC50 and MIC90 for piperacillin against H. influenzae were 0.0625 microg/ml and 0.125 microg/ml, respectively. Tazobactam/piperacillin and piperacillin showed the best results, followed by panipenem, ampicillin, and flomoxef. Piperacillin proved to be very useful for the treatment of pneumonia in children. PMID- 17721686 TI - Antimicrobial resistance of Klebsiella pneumoniae in a Saudi Arabian hospital: results of a 6-year surveillance study, 1998-2003. AB - There are few data regarding the prevalence and trends of antibiotic resistance to Klebsiella pneumoniae in Saudi Arabia over time. Thus, we evaluated the prevalence and the trends in antibiotic resistance of K. pneumoniae at the Saudi Aramco Medical Services Organization over a 6-year period. This was a retrospective study of the in vitro pattern and trends of antibiotic resistance of K. pneumoniae from 1998 to 2003. A total of 3070 distinct isolates of K. pneumoniae were analyzed. Hospital-acquired isolates were more resistant to the tested antibiotics than the outpatient isolates. The resistance rates to cefazolin, trimethoprim-sulfamethoxazole, and ciprofloxacin were 10.8% (n = 79/730), 5% (n = 103/2093), and 15.8% (n = 93/586) for hospital-acquired isolates; and 11% (n = 216/1964), 9.6% (n = 60/624), and 4.4% (n = 68/1526) for outpatient isolates. Resistance to ceftriaxone and ceftazidime was detected in 5.6% (n = 37/659) and 13.8% (n = 24/174) of hospital-acquired isolates and in 1% (n = 17/1713) and 2.7% (n = 6/219) of outpatient isolates, respectively. All tested isolates were susceptible to imipenem. Resistance to three or more classes of antibiotics was present in 1.7% (n = 8/468) of the hospital-acquired isolates and in 0.6% (n = 9/1389) of the outpatient isolates. The data showed increased resistance rates of hospital-acquired isolates of K. pneumoniae to ceftriaxone, gentamicin, and ciprofloxacin; the data also showed that hospital-acquired, rather than outpatient isolates, were more likely to be resistant to multiple antibiotics. PMID- 17721687 TI - Study of nasopharyngeal bacterial flora. Variations in nasopharyngeal bacterial flora in schoolchildren and adults when administered antimicrobial agents. AB - Changes in nasopharyngeal bacterial flora in adults with acute upper respiratory tract infection on administration of antimicrobial agents were investigated, and how these changes contrasted with those in children. Many patients with acute sinusitis due to allergies, and patients with malignancy and diabetes mellitus were included in the investigation. The detection rates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, the major bacteria of acute otitis media (AOM), were 22%, 10%, and 7% respectively, which were significantly lower than those for children. Gram stain examination of nasopharyngeal swab samples showed a significant relation between leukocyte infiltration and the detection amount of S. pneumoniae (P = 0.0086). A significant relation (P = 0.0134) was also observed when H. influenzae was simultaneously detected. No significant change in the three major AOM bacteria present in nasopharyngeal bacterial flora after administration of antimicrobial agents was observed. However, all S. pneumoniae and H. influenzae detected after antimicrobial agent administration had the beta-lactam-resistance gene. It was observed that a significant improvement in leukocyte infiltration occurred 6 to 10 days after antimicrobial agent administration. In contrast, a significant improvement in children was observed at 2 to 5 days. In the adult subjects, this improvement was probably due to spontaneous remission rather than the effect of the antimicrobial agents. Although investigation of the long-term administration of antimicrobial agents was also conducted, its benefits for the patients were not elucidated. PMID- 17721688 TI - A case of cutaneous myiasis due to Dermatobia hominis in Japan. AB - We report the 34th imported case of cutaneous myiasis caused by Dermatobia hominis in Japan, which is not a habitat of the fly. A 41-year-old Japanese man noticed an insect-sting-like papule on his left upper back during his stay in Ecuador in March 2004. After his return home, the lesion gradually increased to become a red subcutaneous nodule with a central pore from which serosanguineous fluid drained. Because antimicrobial treatment under a diagnosis of inflammatory atheroma was ineffective, the lesion was incised and a 3rd instar larva of D. hominis was then found and removed. We checked the literature on D. hominis myiasis reported from Japan, and noted the fact, which nobody had previously pointed out, that in Japan only one case of D. hominis myiasis had been diagnosed correctly before a larva was found, and most of the cases were misdiagnosed and inappropriately treated, including 11 cases given unnecessary resection of the nodules. Doctors in Japan should be aware of myiasis so that patients are neither anxious about the disease nor suffer pain, and doctors avoid performing unnecessary resections of the lesions. PMID- 17721689 TI - Successful treatment of refractory chronic necrotizing pulmonary aspergillosis with micafungin. AB - A 63-year-old man was admitted to our hospital because he complained of fever and productive cough; this was associated with cavitary infiltrates on his chest X ray. Although several antibiotics were given, his symptoms did not improve. Bronchofiberscope investigation yielded Aspergillus fumigatus; thus, he was diagnosed with chronic necrotizing pulmonary aspergillosis. Itraconazole, 200 mg/day, was given, and his symptoms and infiltrates on chest X-ray gradually improved. After 2 months of treatment, new infiltrates appeared on a chest X-ray. Antibacterial agents had also shown no effect, and voriconazole was substituted for itraconazole. However, the infiltrates progressed in spite of the voriconazole administration. We added micafungin to the voriconazole treatment. Both his symptoms and the infiltrates on chest X-rays improved. Because voriconazole is thought to be the most effective agent against Aspergillus spp., it is difficult to treat cases that are refractory to voriconazole. The treatment of this case provides invaluable information on how to treat pulmonary aspergillosis related to diseases other than hematologic malignancies. PMID- 17721690 TI - Outbreak of CTX-M-3-type extended-spectrum beta-lactamase-producing Enterobacter cloacae in a pediatric ward. AB - A first resistant strain of Enterobacter cloacae was isolated from a blood specimen in a pediatric patient with immature teratoma-developed sepsis after combination chemotherapy. The strain produced extended-spectrum beta-lactamase (ESBL), and the same ESBL-producing strains were detected in urine samples from other patients in the pediatric ward. All strains harbored genes for bla (CTX-M 3) by polymerase chain reaction (PCR) and sequencing analysis. Analysis of pulsed field gel electrophoresis revealed that all strains were the same clonal type. These results suggest that ESBL-producing strains might be transmitted in the ward via contact among patients or medical staff. PMID- 17721691 TI - Acute hemorrhagic colitis associated with oral administration of oseltamivir for the treatment of influenza A. AB - The importance of oseltamivir as a strategy for the treatment of influenza has been recognized; however, the risk of acute hemorrhagic colitis should be considered, although it is rare. This report describes a case of acute hemorrhagic colitis in a 61-year-old Japanese man after the oral administration of oseltamivir for influenza A. A definitive diagnosis of influenza A was made using a rapid diagnosis kit. Abdominal pain, diarrhea, and hematochezia occurred the day after the first administration of oseltamivir (The patient had taken two capsules of oseltamivir). Endoscopic examination revealed extensive acute hemorrhagic colitis. Histopathological examination of the colonic mucosa revealed small atrophic glands with partial deciduation of the epithelium and a decrease in the number of goblet cells. Hemorrhage and mild infiltration of inflammatory cells were observed as well. These changes were suggestive of an ischemic change. A culture test showed normal flora. PMID- 17721692 TI - Varicella zoster virus meningoencephalitis accompanied by sporadic skin lesions in an older immunocompetent adult. AB - A previously healthy 75-year-old man complained of persistent fever, headache, nausea, mild gait disturbance, memory disorder, and sporadic vesicular skin lesions. Viral meningoencephalitis was diagnosed, based on cerebrospinal fluid (CSF) analysis. Intensive CSF analysis suggested that the patient's illness was caused by varicella zoster virus (VZV). The patient recovered completely after treatment with intravenous acyclovir. VZV infection should be considered as a possible cause of central nervous system disease, even in an immunocompetent patient. VZV reactivation was strongly suspected because of the results of anti VZV antibody evaluations in serum and CSF, although the skin lesions were not similar to those of herpes zoster. PMID- 17721693 TI - Rapid detection of causative pathogen of peritonitis using in-situ hybridization in a patient with continuous ambulatory peritoneal dialysis. AB - Continuous ambulatory peritoneal dialysis (CAPD) peritonitis is a common problem in patients on peritoneal dialysis, and the bacteriological diagnosis is important for the treatment of this condition. We used Hybrizep (a method for detecting the genes of bacteria ingested in phagocytes), to detect the causative bacterium in a 50-year-old woman receiving peritoneal dialysis who was admitted our hospital with bacterial peritonitis. The test, using peritoneal dialysis fluid, was positive for Streptococcus epidermidis. Vancomycin administration led to a good outcome for this patient. The Hybrizep method (which is available on the Japanese National Health system only for the diagnosis of septicemia) was a useful diagnostic approach for a patient on peritoneal dialysis who had peritonitis. PMID- 17721694 TI - First isolation of blaIMP-7 in a Pseudomonas aeruginosa in Japan. AB - We report here the first isolation in Japan of a carbapenem-resistant Pseudomonas aeruginosa strain that carries the metallo-beta-lactamase gene bla(IMP-7). This isolate revealed high-level resistance to all of the tested antibiotics except for piperacillin, showing a multidrug-resistant phenotype. PMID- 17721695 TI - Auditory processing disorder. PMID- 17721696 TI - Case report: autistic disorder in Kabuki syndrome. PMID- 17721697 TI - Differentiating autism and Asperger syndrome on the basis of language delay or impairment. AB - Asperger syndrome (AS) is differentiated from high-functioning autism (HFA) largely on a history of "language delay." This study examined "specific language impairment" as a predictor of outcome. Language skills of 19 children with AS and 45 with HFA were assessed at 4-6 years of age (Time 1) and 2 years later (Time 2). Children's symptoms and functional outcome scores were assessed every 2 years (Times 3, 4, and 5) until ages 15-17 years old. Regression analysis revealed that specific language impairment at time 2 more often accounted for the greatest variation in outcome scores in adolescence than the standard diagnosis of AS versus HFA based on history of language delay. Diagnostic implications are discussed. PMID- 17721698 TI - Adherence to clinical guidelines in the prevention of coronary heart disease in type II diabetes mellitus. AB - OBJECTIVE: The study aimed to assess adherence of prescribed medication in primary care to nationally recognised guideline criteria using case note review applying a previously developed medication assessment tool for coronary heart disease (MAT-CHD). Setting Primary care medical centre serving 17,991 patients. A sample of 208 from 463 patients with type 2 diabetes aged 20-75 years with or without a history of ischaemic heart disease (IHD). METHOD: Patients' records were accessed via medical and pharmacy databases. The criteria of the 23-item audit tool were applied to medical records from case notes in order to quantify adherence to individual guideline criteria. MAIN OUTCOME MEASURE: Frequency of adherence to agreed definitions of medication use quality criteria. RESULTS: A total of 1,433 guideline criteria were applied and 1,107 (77.2%, CI: 75.0, 79.4) criteria standards were met with 326 (22.7%, CI: 20.6, 25.0) non-adherences. The overall adherence to guideline criteria was significantly lower for secondary prevention than for primary prevention (74.4 vs. 80.1%, P<0.05; Chi square). Justification recorded in the case notes was identified for 54 (17%, CI: 13, 21) of those non-adherences. CONCLUSION: The MAT-CHD highlighted areas for review and possible improvement. The tool can be used in primary care from case record examination and offers a means of co-operation between community pharmacists and general practitioners in clinical guideline implementation. PMID- 17721700 TI - How many gamergates is an ant queen worth? AB - Ant reproductives exhibit different morphological adaptations linked to dispersal and fertility. By reviewing the literature on taxa where workers can reproduce sexually (i.e. become gamergates) we show that (1) species with a single gamergate generally have lost the winged queen caste, whereas only half of the species with several gamergates have, and (2) single-gamergate species have smaller colonies than multiple-gamergate species. Comparison with "classical" ants without gamergates, where having one vs having several winged queens are two distinct syndromes, suggests that having one vs having several gamergates are not. Gamergate number does not affect the success of colony fission, but retention of the queen caste permits the option of independent foundation. PMID- 17721699 TI - Measuring health-related quality of life in drug clinical trials: is it given due importance? AB - AIM OF THE REVIEW: Efficacy estimations of drug clinical trials have been based on clinical measurements and survival rates. However, advances in psychometric techniques have allowed to incorporate a new dimension based on quality of life. Questionnaires aimed at measuring patients' health status outlook, now enable us to quantify the loss of quality of life caused by disease and the improvement that can be achieved by pharmacological treatments. The Aim of this study is to make a quantitative evaluation of the use of health related quality of life (HRQL) measures in drug clinical trials. METHODS: A systematic review was performed, in duplicate, of the five journals with highest contribution to the ACP Journal Club, i.e. New England Journal of Medicine, JAMA, The Lancet, Annals of Internal Medicine and the British Medical Journal. HRQL measures were evaluated in published articles referring to drug clinical trials. RESULTS: We identified 193 articles that reported the results of clinical trials, of which 28 included QOL measures as secondary end points and two as primary end points: in total, these comprised 16% of the articles analysed. Discussion Without considering the relevance of HRQL measures as a tool in the allocation of resources, it should be included as a health outcome dimension in drug clinical trials. The absence of this evaluation in studies about chronic diseases that affects patients' daily life activities would not be justified. CONCLUSIONS: HRQL measures are not used on a regular basis in drug clinical trials that are reported in the relevant literature. Systematic incorporation of QOL measures into clinical trials would make it possible to measure the benefit obtained from drug treatments taking into account the patients' perceptions. Moreover, it would encourage the development of prospective cost-effectiveness studies with patient recorded data in the context of clinical trials. Our findings have a direct impact on practice. Being conscious of the low use of HRQL in clinical trials, it could contribute to increase the demand for these measures by health care professionals. The manuscript is also a useful tool to identify where basic concepts about HRQL measures can be found. PMID- 17721701 TI - Light microscopic histology of supraspinatus tendon ruptures. AB - We analysed the morphological features of the human surgical specimens of supraspinatus tendon from patients with rotator cuff tears. Tendon samples were harvested from 31 subjects (21 men and 10 women; mean age 51 years, range 38-64) who underwent arthroscopic repair of a rotator cuff tear, and from five male patients who died of cardiovascular events (mean age, 69.6 years). Histological examination was performed using Haematoxylin and Eosin, Masson's Trichrome and Van Gieson's connective tissue stain. The specimens were examined twice by the same examiner under white light and polarized light microscopy. Particular effort was made to assess any evidence of the changes associated with tendinopathy. Within each specific category of tendon abnormalities, the chi-square test showed significant differences between the control and ruptured tendons (P < 0.05). Using the kappa statistics, the agreement between the two readings ranged from 0.57 to 0.84. We found thinning and disorientation of collagen fibres and chondroid metaplasia to be more pronounced on the articular side of the specimens from patients with rotator cuff tear (P < 0.05). The present study provides a description of the histological architecture of human surgical specimens of normal supraspinatus tendon from patients with rotator cuff tears and demonstrates more frequent tendon changes on the articular side of the rotator cuff. PMID- 17721702 TI - Ultrasound- and Doppler-guided arthroscopic shaving to treat Jumper's knee: a technical note. AB - Here we present a new technique for arthroscopic treatment of patellar tendinopthy-Jumper's knee, were arthroscopic shaving and Ultrasound + Doppler examination are performed simultaneously. Using this technique, the tendon and the areas with structural tendon changes and high blood flow are continuously demonstrated in the operating field. By this, the shaving procedure can be more exactly addressed to the area of interest on the dorsal surface of the tendon, and the trauma to the Hoffa fat pad and the tendon is minimized. PMID- 17721704 TI - Is the brain biopsy obligatory or not for the diagnosis of Schilder's disease? Review of the literature. AB - BACKGROUND: Schilder's myelinoclastic diffuse sclerosis (Schilder's disease) is a rare demyelinating disorder. Clinical features and neuroimaging findings of this disease might mimic an intra-cranial mass lesion including an abscess or a tumour. CASE REPORT: Clinical and radiological findings of two children with the diagnosis of Shilder's disease are reported, and the role of brain biopsy as a diagnostic tool is discussed. PMID- 17721703 TI - Key clinical issues in renal cancer: a challenge for proteomics. AB - Renal cancer has many clinical challenges which proteomics is ideally placed to address. The issues cover all aspects of the disease including diagnosis, prognosis, treatment selection and monitoring to detect metastatic disease. In all cases novel biomarkers would considerably help in clinical management and with the relative resistance to conventional chemotherapy and radiotherapy, a better understanding of the underlying pathogenesis may contribute to the much needed development of novel therapeutic targets and the better use of promising new anti-angiogenic treatments. This review briefly highlights some of the clinical issues and describes proteomics-based approaches generally, before focussing on reviewing the proteomic studies to date in this area. PMID- 17721705 TI - [Orthoses for rheumatic hand deformities]. AB - Treatment of rheumatic hand deformities is a very sensitive task, requiring profound knowledge of functional anatomy as well as extensive rheumatologic experience. Assistive devices such as orthoses in the therapy of typical deformities aim to prevent continuing loss of function. Furthermore reduction of pain, economization of movements and maintaining postoperative results are important. Contraindications for surgical interventions are also an indication. Static orthoses are to be distinguished from individually produced dynamic devices, which may protect anatomical structures while providing relatively free motion. The indication for this treatment must be agreed by the physician in charge, the patient and the occupational therapist together, assisting functional exercises are strongly recommended. The condition of the skin must be considered and regular follow-up has to be arranged. Each region of the hand and characteristic deformities require individual orthotic devices, according to the capabilities of the patient. The patient's possible improvement of daily activities in relation to the disadvantages of having to use orthoses determines the therapy. Given indications for surgical procedures are taken into consideration from the onset of the treatment plan. PMID- 17721706 TI - [Conservative local therapy of inflammation of joints: local invasive forms of therapy]. AB - Local invasive procedures represent possibilities for the treatment of arthritic swollen joints without surgical interventions, when general measures alone are not successful and intra-articular injections are of utmost importance in this context. The differences between degenerative and rheumatologic diseases must be considered as well as possible specific adverse reactions, side effects and contraindications. The technical intervention is performed according to the guidelines of scientific societies such as the Scientific Medical Profession Society (AWMF). Cortisone and radiosynoviorthesis/chemosynoviorthesis are suitable for activated rheumatic and degenerative joints, low-grade radiation therapy or infiltration of hyaluronic acid is recommended for relief in cases of arthritic inflammation. The combination of arthroscopic synovectomy and subsequent radiosynoviorthesis in the early stages of rheumatically swollen joints show the best results with respect to regression prophylaxis and slowing the process of rapidly progressing destruction of chondral surfaces and distension of the capsules and ligaments. PMID- 17721707 TI - Increase in the relative expression of tau with four microtubule binding repeat regions in frontotemporal lobar degeneration and progressive supranuclear palsy brains. AB - Some cases of familial frontotemporal dementia (FTD) leading to frontotemporal lobar degeneration (FTLD) are caused by mutations in tau on chromosome 17 (FTDP 17). Certain mutations alter the ratio between four (4R tau) and three (3R tau) repeat tau isoforms whereas cases with progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) mainly have 4R tau brain pathology. We assessed tau mRNA and protein levels in frontal cortex from 15 sporadic FTLD, 21 PSP, 5 CBD, 15 Alzheimer's disease (AD) and 16 control brains. Moreover, we investigated the disease association and possible tau splicing effects of the tau H1 haplotype. Cases with FTLD and PSP had lower tau mRNA levels than control brains. When analyzing 4R tau and 3R tau mRNA separately, control subjects displayed a 4R tau/3R tau ratio of 0.48. Surprisingly, FTLD brains displayed a more elevated ratio (1.32) than PSP brains (1.12). Also, several FTLD and PSP cases had higher 4R tau/3R tau mRNA than FTDP-17 cases, included as reference tissues, and the ratio increase was seen regardless of underlying histopathology, i.e. both for tau-positive and tau-negative FTLD cases. Furthermore, total tau protein levels were slightly decreased in both FTLD and AD as compared to control subjects. Finally, we confirmed the association of tau H1 with PSP, but could not find any haplotype-related effect on tau exon 10 splicing. In conclusion, we demonstrated increased but largely variable 4R tau/3R tau mRNA ratios in FTLD and PSP cases, suggesting heterogeneous pathophysiological processes within these disorders. PMID- 17721708 TI - A new methodological approach to assess cardiac work by pressure-volume and stress-length relations in patients with aortic valve stenosis and dilated cardiomyopathy. AB - In experimental animals, cardiac work is derived from pressure-volume area and analyzed further using stress-length relations. Lack of methods for determining accurately myocardial mass has until now prevented the use of stress-length relations in patients. We hypothesized, therefore, that not only pressure-volume loops but also stress-length diagrams can be derived from cardiac volume and cardiac mass as assessed by cardiac magnetic resonance imaging (CMR) and invasively measured pressure. Left ventricular (LV) volume and myocardial mass were assessed in seven patients with aortic valve stenosis (AS), eight with dilated cardiomyopathy (DCM), and eight controls using electrocardiogram (ECG) gated CMR. LV pressure was measured invasively. Pressure-volume curves were calculated based on ECG triggering. Stroke work was assessed as area within the pressure-volume loop. LV wall stress was calculated using a thick-wall sphere model. Similarly, stress-length loops were calculated to quantify stress-length based work. Taking the LV geometry into account, the normalization with regard to ventricular circumference resulted in "myocardial work." Patients with AS (valve area 0.73+/-0.18 cm(2)) exhibited an increased LV myocardial mass when compared with controls (P<0.05). LV wall stress was increased in DCM but not in AS. Stroke work of AS was unchanged when compared with controls (0.539+/-0.272 vs 0.621+/ 0.138 Nm, not significant), whereas DCM exhibited a significant depression (0.367+/-0.157 Nm, P<0.05). Myocardial work was significantly reduced in both AS and DCM when compared with controls (129.8+/-69.6, 200.6+/-80.1, 332.2+/-89.6 Nm/m(2), P<0.05), also after normalization (7.40+/-5.07, 6.27+/-3.20, 14.6+/-4.07 Nm/m(2), P<0.001). It is feasible to obtain LV pressure-volume and stress-length diagrams in patients based on the present novel methodological approach of using CMR and invasive pressure measurement. Myocardial work was reduced in patients with DCM and noteworthy also in AS, while stroke work was reduced in DCM only. Most likely, deterioration of myocardial work is crucial for the prognosis. It is suggested to include these basic physiological procedures in the clinical assessment of the pump function of the heart. PMID- 17721709 TI - The genetic basic and fine-mapping of a stable quantitative-trait loci for aluminium tolerance in rice. AB - Aluminium (Al) toxicity is a primary cause of low rice productivity in acid soils. We have mapped a number of quantitative-trait loci (QTL) controlling Al tolerance in a recombinant inbred line population derived from a cross between the tolerant japonica cultivar Asominori and the sensitive indica cultivar IR24. Tolerance was assessed on the basis of relative root elongation. QTL were detected on chromosomes 1, 9, and 11, with the percentages of phenotypic variance explained ranging from 13.5 to 17.7%. Alleles from Asominori at all three QTL were associated with increased Al tolerance. qRRE-9 is expressed both in the genetic background of IR24 and in an Asominori/IR24-mixed background. qRRE-9 was reduced to the single recessive Mendelian factor Alt-9. High-resolution genetic and physical maps were constructed for Alt-9 in a BC(3)F(2) population of 1,043 individuals. Alt-9 maps between RM24702 and ID47-2 on chromosome 9, and co segregates with RM5765. PMID- 17721710 TI - Molecular cloning and characterization of WD40-repeat protein from Clonorchis sinensis. AB - WD40-repeat proteins have four to eight repeating units flanked by Gly-His (GH) and Trp-Asp (WD) at both termini and folds into a beta-propeller. A polypeptide deduced from a Clonorchis sinensis cDNA clone analyzed to have seven WD40-repeats and predicted to form a beta-propeller (CsWD1). The CsWD1 protein was expressed stage-specifically in the metacercariae and localized in the tegumental syncytium. The CsWD1 protein is suggested to serve as a platform for interacting partner proteins in the tegumental syncytium of C. sinensis metacercariae. PMID- 17721711 TI - Are the spines of calf, pig and sheep suitable models for pre-clinical implant tests? AB - Pre-clinical in vitro tests are needed to evaluate the biomechanical performance of new spinal implants. For such experiments large animal models are frequently used. Whether these models allow any conclusions concerning the implant's performance in humans is difficult to answer. The aim of the present study was to investigate whether calf, pig or sheep spine specimens may be used to replace human specimens in in vitro flexibility and cyclic loading tests with two different implant types. First, a dynamic and a rigid fixator were tested using six human, six calf, six pig and six sheep thoracolumbar spine specimens. Standard flexibility tests were carried out in a spine tester in flexion/extension, lateral bending and axial rotation in the intact state, after nucleotomy and after implantation. Then, the Coflex interspinous implant was tested for flexibility and intradiscal pressure using another six human and six calf lumbar spine segments. Loading was carried out as described above in the intact condition, after creation of a defect and after implantation. The fixators were most easily implantable into the calf. Qualitatively, they had similar effects on ROM in all species, however, the degree of stability achieved differed. Especially in axial rotation, the ROM of sheep, pig and calf was partially less than half the human ROM. Similarly, implantation of the Coflex interspinous implant caused the ROM to either increase in both species or to decrease in both of them, however, quantitatively, differences were observed. This was also the case for the intradiscal pressure. In conclusion, animal species, especially the calf, may be used to get a first idea of how a new pedicle screw system or an interspinous implant behaves in in vitro flexibility tests. However, the effects on ROM and intradiscal pressure have to be expected to differ in magnitude between animal and human. Therefore, the last step in pre clinical implant testing should always be an experiment with human specimens. PMID- 17721712 TI - The influence of work-related exposures on the prognosis of neck/shoulder pain. AB - To determine associations between work-related exposures and the prognosis of self-reported neck/shoulder pain. This prospective cohort study was based on 803 working subjects who reported neck/shoulder pain at baseline. The proportion of subjects who 5-6 years later were symptom-free was calculated. Data concerning work-related biomechanical, psychosocial, and organizational exposures were collected at baseline. The Cox regression analyses were used to calculate the relative chances (RC) of being symptom-free at the end of the study for single exposures, and also for up to three simultaneous work-related exposures. Adjustments were made for sex and age. Only 36% of the subjects were symptom-free 5-6 years later. The relative chance for being symptom-free at the end of the study was 1.32 (95% CI = 0.99-1.74) for subjects who were exposed to sitting > or =75% of the working time and 1.53 (95% CI = 1.02-2.29) for subjects who were exposed to job strain, i.e., the combination of high demands and low decision latitude. The relative chance of being symptom-free at the end of the study was 0.61 (95% CI = 0.40-0.94) for subjects with at least two out of three simultaneous biomechanical exposures at work; manual handling, working with the hands above shoulder level, and working with vibrating tools. In a heterogeneous population with moderate nonspecific neck/shoulder pain, sedentary work enhanced the chance of being symptom-free 5-6 years later, whereas simultaneous exposures to at least two of manual handling, working with hands above shoulder level and working with vibrating tools were associated with a lower chance of being symptom free at the end of the study. This could imply that subjects with neck/shoulder pain should avoid such simultaneous exposures. PMID- 17721714 TI - Gradient of deficit in cone responses in the incomplete form of congenital stationary night blindness revealed by multifocal electroretinography. AB - Multifocal electroretinograms were recorded in one case of incomplete form of congenital stationary night blindness. First order kernel revealed reduced cone macular P1 responses with normal implicit time (22.7 nV, 33.3 ms; normal 43.3 +/- 8.2 nV, 32.7 +/- 0.6 ms) whereas more peripheral responses exhibited low responses of extremely delayed implicit time (5.1 nV, 47.5 ms; normal 7.4 +/- 2.1 nV, 32.3 +/- 0.8 ms). Responses from the first slice of the second kernel were present in the macular area but absent from the more peripheral areas. In comparison, mfERGs in the complete form of CSNB showed normal amplitude but slightly delayed responses at all eccentricities and normal second kernel responses. Results are discussed in terms of the dichotomy in synaptic transmission between macular and peripheral cones. PMID- 17721713 TI - Effects of a cervical disc prosthesis on maintaining sagittal alignment of the functional spinal unit and overall sagittal balance of the cervical spine. AB - The object of this study is to review the early clinical results and radiographic outcomes following insertion of the Bryan Cervical Disc Prosthesis (Medtronic Sofamor Danek, Memphis, TN), together with its effect on maintaining sagittal alignment of the functional spinal unit (FSU) and overall sagittal balance of the cervical spine for the treatment of single-level or two-level symptomatic disc disease. Forty-seven patients with symptomatic single or two-level cervical disc disease who received the Bryan Cervical Artificial Disc were reviewed prospectively. A total of 55 Bryan disc were placed in 47 patients. A single level procedure was performed in 39 patients and a two-level procedure in the other eight. Radiographic and clinical assessments were made preoperatively and at 1.5, 3, 6, 9, 12, and 18 and up to 33 months postoperatively. Mean follow-up duration was 24 months, ranging from 13 to 33 months. Periods were categorized as early follow up (1.5-3 months) and late follow up (6-33 months). The visual analogue scale (VAS), neck disability index(NDI), Odom's criteria were used to assess pain and clinical outcomes. Static and dynamic radiographs were measured by hand and computer to determine the range of motion (ROM), the angle of the functional segmental unit (FSU), and the overall cervical alignment (C2-7 Cobb angle). With all of these data, we evaluated the change of the preoperative lordosis (or kyphosis) of the FSU and Overall sagittal balance of the cervical spine during the follow-up period. There was a statistically significant improvement in the VAS score from 7.0 +/- 2.6 to 2.0 +/- 1.5 (paired-t test, P = 0.000), and in the NDI from 21.5 +/- 5.5 to 4.5 +/- 3.9 (paired-t test P = 0.000). All of the patients were satisfied with the surgical results by Odom's criteria. The postoperative ROM of the implanted level was preserved without significant difference from preoperative ROM of the operated level. Only 36% of patients with a preoperative lordotic sagittal orientation of the FSU were able to maintain lordosis following surgery. However, the overall sagittal alignment of the cervical spine was preserved in 86% of cases at the final follow up. Interestingly, preoperatively kyphotic FSU resulted in lordotic FSU in 13% of patients during the late follow-up, and preoperatively kyphotic overall cervical alignment resulted in lordosis in 33% of the patients postoperatively. Clinical results are encouraging, with significant improvement seen in the Bryan Cervical Artificial disc. The Bryan disc preserves motion of the FSU. Although the preoperative lordosis (or kyphosis) of the FSU could not always be maintained during the follow-up period, the overall sagittal balance of the cervical spine was usually preserved. PMID- 17721715 TI - Durability improvement of polymer chamber of pulsatile extracorporeal life support system in terms of mechanical change. AB - Twin Pulse Life Support, T-PLS has received the CE mark (2003) and Korea Food and Drug Administration (KFDA) approval (2004) for short-term application as an Extracorporeal Life Support system (ECLS). T-PLS's original intention was to apply for not only short-term but also long-term application such as Extracorporeal ventricular assist device (VAD). Hence, a long-term durability test was conducted. The 1-year reliability of the systems tested in this study did not meet the STS/ASAIO standard of 80% reliability with 60% confidence for a 1-year mission life. However, without the disposable units, which are only designed to operate for 6 h, the 1-year reliability exceeded the STS/ASAIO standard of 80% reliability with 60% confidence. In this study, by using the existing analysis methods and analyzing the root cause of the failure used by a numerical analysis. As eliminating or mitigating of the root cause of the failure, we improved the durability of blood chamber and evaluated the performance of the modified system via the hemolysis test. PMID- 17721716 TI - Per-operative infiltration of the rectus sheath in abdominoplasty. PMID- 17721717 TI - The figure-of-eight suture technique used for complicated wound closure. PMID- 17721718 TI - Hemiface rhytidectomy. AB - In the current study, skin flaps raised in the subcutaneous plane were applied for 22 patients who underwent reconstruction for unilateral upper facial skin defects after skin tumor surgery. The defect was reconstructed with flaps designed via procedures similar to classic rhytidectomy techniques using periauricular and temporal skin incisions. Objective assessment of the aesthetic result was possible by comparison with the healthy contralateral side of the face. Immediate postoperative evaluation confirmed facial asymmetry due to unilateral skin tension. High patient acceptance of the procedure, uneventful flap healing, and good aesthetic results were achieved, with almost complete restoration of facial symmetry 1 year postoperatively. In conclusion, unilateral rhytidectomy without plication or resection of the subcutaneous musculoaponeurotic system (SMAS) is an ideal application of aesthetic surgical techniques for the reconstruction of unilateral skin defects. PMID- 17721719 TI - Modified mini-abdominoplasty: navel transposition and horizontal residual scar. AB - The classic mini-abdominoplasty is a surgery generally indicated for cases in which cutaneous laxity of the abdomen's inferior region is associated with adiposity. However, in some cases, the characteristics of the abdomen are such that resort to a traditional mini-abdominoplasty would involve an unsatisfactory final result due to the unavoidable caudalization of the navel. In answer to this problem, Pontes developed the type 4 modified mini-abdominoplasty. This procedure adds to the classic technique a complete resection of the navel and its transposition so that it leaves a residual vertical scar. With our version of the technique, the scar is more aesthetic in shape and appearance, horizontal, and parallel to the suprapubic scar. PMID- 17721720 TI - Endoscopically assisted buttocks augmentation. AB - Body-contouring aesthetic surgery focused on the gluteal region has been increasingly in demand. This article aims to describe the surgical technique, the results, and the complications for 28 women who underwent endoscopically assisted gluteoplasty using high-profile, high-cohesion round silicone implants between 1996 and 2006. The procedure involves precise dissection of the area for implant inclusion under endoscopic visualization, allowing optimization of the aesthetic gain, while minimizing the risks of sciatic nerve injury. Complications requiring surgical reintervention occurred for 7% of the patients. The technique demonstrated itself to be safe, dependable, and easy to learn. PMID- 17721721 TI - Lymph node metastasis density and growth pattern as independent prognostic factors in advanced esophageal squamous cell carcinoma. AB - BACKGROUND: Esophageal cancer is one of the leading types of cancer, and it is a particularly deadly form of malignancy. TNM classification is the most common staging system, but it has been reported that prognosis is not reflected adequately by this classification. The purpose of this study was to clarify independent prognostic factors in esophageal squamous cell carcinoma (ESCC), a dominant type of esophageal cancer in Japan, to broaden the staging system to improve its predictive value. Thus staging could be expanded to make the prognosis a valuable clinical tool, and to improve knowledge of the biological traits of advanced ESCC. METHODS: The present study included 121 patients with advanced ESCC (stage II to IVA) treated by esophagectomy between 1990 and 2003 at the Kitasato University Higashi Hospital. RESULTS: Univariate prognostic analysis of the disease-specific survival revealed that TNM stage (p < 0.0001), lymph node metastasis density over 10% (ND10; p < 0.0001), R-category (p = 0.003), intramural metastasis within the esophagus (IM; p = 0.009), growth pattern (p = 0.01), and size of tumor (p = 0.02) were significantly associated with a poor outcome in advanced ESCC. Multivariate analysis confirmed that growth pattern (p = 0.02, HR = 3.1) and ND10 (p = 0.02, HR = 2.0) were finally remnant prognostic factors independent of TNM stage. Growth pattern was prominent in stage II, whereas ND10 was directly proportional to stage progression and characteristics to stage IV disease. Interestingly, ND20, the most malignant phenotype of ESCC, was the only prognostic determinant, even in stage IV disease. CONCLUSIONS: From the present study, we concluded that progression of lymph node density is characteristic of a life-threatening phenotype of advanced ESCC, and it should be employed as a therapeutic target to improve patient survival. Growth pattern is an alternative target characteristic of less advanced ESCC. Both of these parameters may be applied as useful clinical tools in the management of patients with advanced esophageal cancer. PMID- 17721722 TI - Outcome of segmental gastrectomy versus distal gastrectomy for early gastric cancer. AB - BACKGROUND: Because of the frequent occurrence of postgastrectomy disturbances after distal gastrectomy (DG), segmental gastrectomy (SG) has recently been applied to early gastric cancer (EGC). Outcomes of SG and DG in patients with EGC were compared to clarify the usefulness of SG as a treatment for EGC. METHODS: This retrospective study involved 61 patients with EGC: 28 patients who underwent DG before March 1996 and 33 patients who underwent SG after April 1996 during the period April 1991 through March 2002. Patient and tumor characteristics, operative results, and postoperative outcomes were compared between the two groups. RESULTS: The postoperative/preoperative body weight ratio was higher in the SG group than in the DG group. Early dumping syndrome and reflux gastritis occurred less frequently after SG than after DG. The incidence of postoperative complications was similar in the two groups. All patients remained alive without recurrence during a mean follow-up period of 54.7 months in the SG group and 99.9 months in the DG group. CONCLUSIONS: In comparison to DG, SG is associated with improved postoperative quality of life with no decrease in operative curability of EGC. Thus, SG is a feasible treatment for EGC. PMID- 17721723 TI - Can we make it last? Maintaining benefits achieved with pulmonary rehabilitation. PMID- 17721724 TI - Observations of Forsythia koreana methanol extract on mast cell-mediated allergic reactions in experimental models. AB - To explore effects of Forsythia koreana methanol extract (FKME) on mast cell mediated allergic and inflammatory properties, the effect of FKME was evaluated on compound 48/80-induced systemic anaphylaxis, ear swelling, and anti dinitrophenyl (DNP) immunoglobulin E (IgE)-induced passive cutaneous anaphylaxis (PCA). In addition, the effect of FKME was investigated on the histamine release from rat peritoneal mast cells (RPMCs) stimulated by compound 48/80, which promotes histamine release. The human mast cell line HMC-1 was stimulated by phorbol 12-myristate 13-acetate plus calcium ionophore A23187. Activated HMC-1 can produce several proinflammatory and chemotactic cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-8. Cytokine levels in the culture supernatant were measured by an enzyme-linked immunosorbent assay. Cytotoxicity by FKME was determined by a 3-(4,5-dimethylthiazol-2-yl)-diphenyl tetrazolium bromide (MTT) assay. FKME inhibited compound 48/80-induced systemic anaphylactic shock and ear swelling in mice. When 1 g/kg FKME was pretreated or posttreated with mice, compound 48/80-induced mice morality was 50 and 66.7%, respectively. One gram per kilogram of FKME pretreatment inhibited ear-swelling responses derived from compound 48/80 by 29.75%. A PCA reaction was inhibited by 17.9%. In an in vitro model, FKME (1 mg/ml) inhibited histamine release from the RPMCs by 13.8% and TNF-alpha, IL-6, and IL-8 production from HMC-1 cells by 71.16% (P < 0.001), 86.72% (P < 0.001), and 44.6%, respectively. However, FKME had no cytotoxic effects on cell viability. In conclusion, FKME inhibited not only systemic anaphylaxis and ear swelling induced by compound 48/80 but also inhibited a PCA reaction induced by anti-DNP IgE in vivo. Treatment with FKME showed significant inhibitory effects on histamine, TNF-alpha, IL-6, and IL-8 release from mast cells. PMID- 17721725 TI - Predictors of unprotected sex among young sexually active African American, Hispanic, and White MSM: the importance of ethnicity and culture. AB - Despite the recognized need for culturally tailored HIV prevention interventions for gay, bisexual, and questioning youth, few studies have examined if predictors of unprotected sex vary for youth from different ethnic groups. This study reports on a sample of 189 gay, bisexual, and questioning youth (age 15-22) from three racial/ethnic backgrounds (African American, Hispanic, and White) recruited in Chicago, IL and Miami-Dade and Broward Counties, Florida. For African American youth, being in a long-term relationship, having been kicked out of the home for having sex with men, and younger age at initiation of sexual behavior were associated with unprotected sex. For Hispanic youth, higher ethnic identification and older age at initiation of sexual behavior were associated with unprotected sex. For White youth, no predictors were associated with unprotected sex. Our findings point to the importance of understanding the varying predictors of unprotected sex and integrating them into tailored prevention interventions. PMID- 17721726 TI - Decreased hepatic 5-HT1A receptors during liver regeneration and neoplasia in rats. AB - In the present study we investigated the role of 5-hydroxytryptamine (5-HT) and 5 HT1A receptor during liver regeneration after partial hepatectomy (PH) and N nitrosodiethylamine (NDEA) induced hepatocellular carcinoma in male Wistar rats. 5-HT content was significantly increased during liver regeneration after PH and NDEA induced hepatocellular carcinoma. Scatchard analysis using 8-OH-DPAT, a 5 HT1A specific agonist showed a decreased receptor during liver regeneration after PH and NDEA induced hepatocellular carcinoma. 5-HT when added alone to primary hepatocyte culture did not increase DNA synthesis but was able to increase the EGF mediated DNA synthesis and inhibit the TGF beta 1 mediated DNA synthesis suppression in vitro. This confirmed the co-mitogenic activity of 5-HT. 8-OH-DPAT at a concentration of 10(-4) M inhibited the basal and EGF-mediated DNA synthesis in primary hepatocyte cultures. It also suppressed the TGF beta 1-mediated DNA synthesis suppression. This clearly showed that activated 5-HT1A receptor inhibited hepatocyte DNA synthesis. Our results suggest that decreased hepatic 5 HT1A receptor function during hepatocyte regeneration and neoplasia has clinical significance in the control of cell proliferation. PMID- 17721727 TI - Metabolic and regulatory roles of leucine in neural cells. AB - Dietary leucine transported into the brain parenchyma serves several functions. Most prominent is the role of leucine as a metabolic precursor of fuel molecules, alpha-ketoisocaproate and ketone bodies. As alternatives to glucose, these compounds are forwarded by the producing astrocytes to the adjacent neural cells. Leucine furthermore participates in the maintenance of the nitrogen balance in the glutamate/glutamine cycle pertinent to the neurotransmitter glutamate. Leucine also serves as a regulator of the activity of some enzymes important for brain energy metabolism. Another role of leucine as an informational molecule is in mTOR signaling that participates in the regulation of food ingestion. The importance of leucine for brain function is stressed by the fact that inborn errors in its metabolism cause metabolic diseases often associated with neuropathological symptoms. In this overview, the current knowledge on the metabolic and regulatory roles of this essential amino acid in neural cells are briefly summarized. PMID- 17721728 TI - Effects of gastric electrical stimulation with short pulses and long pulses on gastric dysrhythmia and signs induced by vasopressin in dogs. AB - AIMS: This study was to investigate the effect of gastric electrical stimulation (GES) with short pulses, long pulses, short-pulse trains or long-pulse trains on gastric dysrhythmia and motion-sickness signs induced by vasopressin. METHODS: Seven male beagle dogs implanted with four pairs of electrodes on gastric serosa were studied. The study was performed in six sessions in a randomized order. In session 1 or 2, either saline or vasopressin was infused without GES. In session 3, 4, 5 and 6, GES with short pulses, long pulses, trains of short pulses or trains of long pulses was performed before and during vasopressin infusion. Gastric slow waves and motion-sickness signs were recorded in each session. RESULTS: (1) Vasopressin induced gastric dysrhythmia and motion sickness-like signs (ANOVA, P < 0.001). (2) GES with short pulses or trains of short pulses was capable of preventing vasopressin-induced emetic response (P < 0.001), but did not normalize gastric dysrhythmia. (3) GES with long pulses or trains of long pulses was able to normalize gastric dysrhythmia induced by vasopressin (P < 0.001), but showed no effects on vasopressin-induced motion-sickness signs. CONCLUSION: GES with short pulses or trains of short pulses prevents vasopressin induced emetic response with no improvement in gastric dysrhythmia. GES with long pulses or trains of long pulses normalizes gastric dysrhythmia induced by vasopressin with no effects on signs. PMID- 17721729 TI - Culture duration modulates collagen hydrolysate-induced tissue remodeling in chondrocyte-seeded agarose hydrogels. AB - Media supplementation with collagen hydrolysate was hypothesized to increase the collagen content in engineered cartilage. By d28, hydrolysate at 0.5 mg/mL increased type II collagen content and 1 mg/mL increased mechanical properties, total collagen content, and type II collagen content over controls. By d42, however, controls possessed the highest GAG content and compressive Young's modulus. Real-time PCR found that 1 mg/mL increased type II collagen gene expression in d0 constructs, but increased MMP expression with no effect on type II collagen on d28. A 10 mg/mL concentration produced the lowest tissue properties, the lowest type II collagen gene expression on d0, and the highest MMP gene expression on d28. These results indicate that the duration of culture modulates the response of chondrocytes to collagen hydrolysate in 3D culture, transforming the response from positive to negative. Therefore, collagen hydrolysate as a media supplement is not a viable long-term method to improve the collagen content of engineered cartilage tissue. PMID- 17721730 TI - Static magnetic fields promote osteoblast-like cells differentiation via increasing the membrane rigidity. AB - The aim of this study was to test the differentiative effects of osteoblasts after treatment with a static magnetic field (SMF). MG63 osteoblast-like cells were exposed to a 0.4-T SMF. The differentiation markers were assessed by observing the changes in alkaline phosphatase activity and electron microscopy images. Membrane fluidity was used to evaluate alterations in the biophysical properties of the cellular membranes after the SMF simulation. Our results show that SMF exposure increases alkaline phosphatase activity and extracellular matrix release in MG63 cells. On the other hand, MG63 cells exposed to a 0.4-T SMF exhibited a significant increase in fluorescence anisotropy at 6 h, with a significant reduction in the proliferation effects of growth factors noted at 24 h. Based on these findings, the authors suggest that one of the possible mechanisms that SMF affects osteoblastic maturation is by increasing the membrane rigidity and reducing the proliferation-promoting effects of growth factors at the membrane domain. PMID- 17721731 TI - Determination of iodine in low mass human hair samples by inductively coupled plasma mass spectrometry. PMID- 17721732 TI - Levels of cadmium and lead in tissues of freshwater fish (Clarias batrachus L.) and chicken in Western UP (India). PMID- 17721733 TI - Biodecolorization of azo dye acid red B under high salinity condition. AB - The study was conducted by a novel salt tolerant bacterium Gracilibacillus sp. GTY. The strain was identified on the basis of morphological and physio biochemical characteristics, and 16S rDNA sequence analysis. Decolorization was performed by growing and resting cells, as well as by extracted azo reductase. Strain grown in the media containing 15% (w/v) of NaCl showed the best performance in decolorization. Decolorization was observed by the UV-visible absorbance spectra. The maximum absorption peak in the visible area decreased to a minimum level after 96 h of incubation. On the other hand, strain grown in very low, or high concentrations, of salt did not show good performance in decolorization; suggesting that salt concentrations in the surroundings control the production of azo reductase. PMID- 17721734 TI - 58-year-old patient with cardiac arrest due to coronary spasm. PMID- 17721735 TI - Quality of life and occurrence of atrial fibrillation in long-term follow-up of common type atrial flutter ablation: ablation with irrigated 5 mm tip and conventional 8 mm tip electrodes. AB - OBJECTIVES: The ablation of common type atrial flutter is mainly performed by two approved techniques, whose efficacy and outcome in terms of quality of life have not been evaluated so far in a long-term follow-up study over years. A high proportion of patients suffer from coexistent atrial fibrillation, which may worsen the ablation result. The question arises whether one technique is more effective than the other when immediate ablation results, the occurrence of atrial fibrillation and the quality of life are compared. Considering these facts, it is reasonable to think about new ablation strategies for common type atrial flutter in the era of new concepts in catheter ablation of atrial fibrillation. METHODS: In a retrospective study we evaluated a detailed questionnaire in 132 patients who underwent ablation of common type between 1999 and 2004. Radiofrequency ablation was performed irrespective of coexistent atrial fibrillation either with an irrigated tip or the 8 mm tip electrode. Acute and long-term ablation outcome, and the associated quality of life, pre-, under- and post-ablation was compared in the two different ablation groups. Recurrent tachycardia were re-evaluated by 12 lead ECG analysis and assessed for both ablation groups. RESULTS: 88 (67%) of the 132 patients contacted answered the questionnaire polling the perceived benefits of the procedure. Of the other 44 patients (33%); 4 (3%) had died, 7 (5.3%) had moved, 33 patients (25%) could not be included due to missing or incoherent answers. Independent of the ablation technique there was a high acute and long-term ablation success rate at about 95%. After a mean of 3 years of follow-up this benefit persists in spite of a high proportion of recurrent tachycardia, mainly atrial fibrillation (55/88 patients, 59.1%). Despite the occurrence of secondary tachycardia, there was a high significant long-term symptomatic benefit in the state of healthy and daily practice work, evaluated with a p-value of < 0.0005. The frequency of episodes and the symptom "tachycardia" were significantly reduced after effective ablation of common type atrial flutter, p-values of 0.003 and 0.002, respectively. Therefore the need for hospitalization was significant reduced (p = 0.001). Comparison of both approaches revealed that there was no significant difference related to the incidence and occurrence of atrial fibrillation. CONCLUSIONS: The two mainly accepted and applied techniques for the ablation of common type atrial flutter show an excellent outcome under the aspect of ablation efficacy and quality of life in longterm follow-up. Three years after the ablation procedure the majority of patients consider the intervention beneficial. Despite the relatively high appearance of atrial fibrillation in the long-term follow-up this effect is still traceable. PMID- 17721736 TI - Risk factors of nosocomial infection with extended-spectrum beta-lactamase producing bacteria in a neonatal intensive care unit in China. AB - BACKGROUND: To study risk factors of neonatal nosocomial infection caused by extended-spectrum beta-lactamase (ESBL)-producing bacteria in a neonatal intensive care unit (NICU). PATIENTS AND METHODS: A retrospective cohort study was conducted in a university hospital NICU in south China. Medical records of neonatal nosocomial infection caused by Escherichia coli or Klebsiella pneumoniae were reviewed. Twenty-two neonates infected with ESBL-producing bacteria (case patients) were compared with 17 patients infected with non-ESBL producing strains (controls). Univariable and multivariable logistic regression were performed to analyze risk factors for infection with ESBL-producing strains. The spectrum of antimicrobial resistance of ESBL-positive E. coli or K. pneumoniae was also examined. RESULTS: Both univariable and multivariable logistic regression analysis revealed that preterm low birth weight, prolonged mechanical ventilation (> or = 7 days) and prior use of third-generation cephalosporins were risks factors for ESBL-producing E. coli or K. pneumoniae infection (p < 0.05), with an odd ratio of 6.43 (95% CI: 1.51-27.44; p = 0.017), 7.50 (95% CI: 1.38-40.88; p = 0.017) and 9.00 (95% CI: 1.65-49.14; p = 0.008) respectively. However, the length of hospital stay before isolation of pathogens, endotracheal intubation, presence of a central venous catheter, days on third-generation cephalosporins and prior use of beta-lactamase inhibitors were not statistically significant (p > 0.05). Resistance of ESBL-positive strains to piperacillin, tobramycin, aztreonam and cephalosporins was significantly higher than that of ESBL-negative ones (p < 0.05). ESBL-producing strains appeared susceptible to carbapenem, fluoroquinolones, and beta-lactamase inhibitor combination piperacillin tazobactam. CONCLUSIONS: Preterm low birth weight, prolonged mechanical ventilation and prior use of third-generation cephalosporins are risks factors for nosocomial infection with ESBL-producing bacteria in NICU. PMID- 17721738 TI - Gangrenous, hemorrhagic, bullous cellulitis associated with pseudomonas aeruginosa in a patient with Waldenstrom's macroglobulinemia. AB - BACKGROUND: Patients with Waldenstrom's macroglobulinemia may manifest several types of skin lesions. We present our experience with a patient with the disease that adds to the literature on the topic. CASE DESCRIPTION: A 57-year-old man with history of multiple sclerosis and Waldenstrom's macroglobulinemia was admitted to the intensive care unit in shock. His family members reported that the patient had complained of fever and the gradual development of gangrenous, hemorrhagic, bullous cellulitis lesions on the abdomen and lower extremities for 7 days prior to his admission to the hospital. Pseudomonas aeruginosa was isolated from fluid specimens collected from the cutaneous lesions. Appropriate antimicrobial treatment including continuous intravenous administration of meropenem (6 g every 24 h) led to the cure of the infection. CONCLUSIONS: We postulate that the underlying Waldenstrom's macroglobulinemia contributed to the pathophysiology of the development of the rare skin manifestations of the infection observed in our patient. PMID- 17721737 TI - Prevalence of enterotoxin producing Staphylococcus aureus in stools of patients with nosocomial diarrhea. AB - BACKGROUND: Nosocomial diarrhea causes prolonged hospital stay leading to additional diagnostic and therapeutic procedures resulting in higher costs. A total of 20%-25% of antibiotic-associated diarrhea (AAD) cases are attributed to Clostridium difficile. Other microorganisms like Clostridium perfringens and Staphylococcus aureus are discussed to be associated with AAD. PATIENTS AND METHODS: This study evaluated the prevalence of enterotoxigenic S. aureus in stool samples submitted to the laboratory with the diagnosis nosocomial diarrhea. A total of 2,727 stools from clinical patients were investigated for S. aureus and C. difficile. Samples were cultured for both bacteria and a C. difficile toxin A and B assay was performed from all stools. Isolated S. aureus were investigated for enterotoxin production and for resistance against methicillin. In addition, both assays were evaluated for determination of S. aureus enterotoxins directly in stool samples. RESULTS: Out of 2,727 stools investigated, 198 grew S. aureus and 148 C. difficile. Toxins A/B from C. difficile were detected in 184 stools. A total of 114 S. aureus strains produced the following enterotoxins in vitro: A, 36; B, 20; C, 19; D, 68; E, 2. Both pathogens were found in 25 stools. Twenty-nine (14.6%) S. aureus strains were identified as methicillin-resistant. The two toxin assays evaluated in this study were not able to detect S. aureus enterotoxins directly in stools. CONCLUSION: The role of enterotoxigenic S. aureus in the pathogenesis of nosocomial and AAD needs further consideration. It might be necessary to investigate stool samples from patients with AAD/nosocomial diarrhea for S. aureus on a routine basis. PMID- 17721739 TI - Disseminated invasive aspergillosis with cerebral involvement successfully treated with caspofungin and voriconazole. AB - We describe a case of cerebral aspergillosis which was successfully treated with a combination of caspofungin and voriconazole. The patient remains in remission 18 months after stopping antifungal treatment. We discuss primary and salvage therapy of invasive aspergillosis with focus on cerebral involvement. Since historical data showed a fatal outcome in most cases, amphotericin B does not cross the blood brain barrier while voriconazole does, we chose a combination of voriconazole plus caspofungin as primary therapy. PMID- 17721740 TI - Pulmonary edema due to Plasmodium vivax malaria in an American missionary. AB - Pulmonary edema is a recognized complication of Plasmodium falciparum malaria but is uncommon with Plasmodium vivax infection. We report the case of a non-immune adult with imported P. vivax malaria who developed pulmonary edema during treatment. The case was further complicated by a recurrent malaria episode after failure of acute quinine and doxycycline treatment followed by terminal primaquine therapy. Prompt recognition and appropriate management of pulmonary edema is needed for optimal outcomes of P. vivax infection, as well as awareness of the potential failure of terminal therapy for liver hypnozoites. PMID- 17721741 TI - The influence of acute-phase levels of haemostatic factors on reperfusion and mortality in patients with acute myocardial infarction treated with streptokinase. AB - BACKGROUND: The fibrinolytic system and von Willebrand factor (vWF) have been shown to play a role as risk factors for myocardial infarction. We performed this prospective cohort study to determine if components in the fibrinolytic system or vWF before or during treatment of AMI with streptokinase (SK) could predict reperfusion, recurrent ischaemia, reinfarction or mortality at one year, or mortality at five years. Reperfusion and recurrent ischaemia were assessed by continuous vectorcardiography. The setting was Umea university hospital and Skelleftea county hospital, Sweden. RESULTS: 139 patients were included; successful reperfusion was obtained in 53%. tPA activity, PAI-activity, PAI-mass concentration and vWF were analysed immediately on arrival and after 4 and 10 h. High fibrinolytic activity, measured as tPA activity > 25 U/L after the start of treatment, was associated with reperfusion. No significant associations between pre-treatment levels of the fibrinolytic variables or vWF and reperfusion or recurrent ischaemia were found. Elevated levels of PAI-1 mass concentration and PAI-1 activity after the start of SK treatment were associated with a higher risk for death at one year, but not at five years. High levels of vWF were associated with worse prognosis but not when corrected for age. CONCLUSION: Pre-treatment levels of PAI-1, vWF and tPA activity showed no association with reperfusion or recurrent ischaemia. Elevated levels of PAI-1 activity after the start of treatment were associated with worse prognosis. PMID- 17721742 TI - Plasminogen activator inhibitor-1 4G4G genotype is associated with myocardial infarction but not with stable coronary artery disease. AB - BACKGROUND: A case control study was conducted to test the hypothesis that plasminogen activator inhibitor type-1 (PAI-1) 4G/5G gene polymorphism confers an increased risk for myocardial infarction (MI) in patients with known coronary atherosclerosis. METHODS: One hundred fifty-six consecutive patients who presented with acute MI and 111 stable coronary artery disease (SCAD) patients with documented critical coronary artery stenoses were prospectively enrolled. PAI-1 4G/5G gene polymorphism and conventional atherosclerotic risk factors were studied in all patients. PAI-1 4G/5G gene polymorphism was studied in another 281 healthy blood bank donors. RESULTS: The frequency 4G4G genotype was significantly higher in the MI group as compared to SCAD group (32.7% vs. 15.3%, P = 0.001) while it was not statistically significant between MI and healthy control groups (32.7% vs. 26.0%, P = 0.136). Comparing with healthy controls SCAD group had significantly lower frequency of 4G4G genotype (P = 0.024). In comparison with SCAD group PAI-1 4G/4G genotype, male sex and smoking habits favored to MI in univariate analysis with a P value of less than 0.2. These variables were included in multivariate regression model to estimate the associated risk for MI. PAI-1 4G/4G genotype was the only independent variable (OR 2.67, 95%CI 1.43-4.96, P = 0.002) associated with MI in this regression model. Comparing with healthy control group 4G4G genotype was not associated with MI (OR 1.38, 95%CI 0.90 2.12). However, presence of 4G4G genotype had a protective effect against development of SCAD (OR 0.52, 96%CI 0.29-0.92). CONCLUSION: Compared to patients with critical coronary stenoses, PAI-1 4G/4G genotype was found to be an independent predictor for development of MI in this population. PAI-1 4G4G genotype have a protective effect against development of high grade stable coronary stenoses. PMID- 17721743 TI - Inflammation and melanoma growth and metastasis: the role of platelet-activating factor (PAF) and its receptor. AB - An inflammatory tumor microenvironment fosters tumor growth, angiogenesis and metastatic progression. Platelet-activating factor (PAF) is an inflammatory biolipid produced from membrane glycerophospholipids. Through the activity of its G-protein coupled receptor, PAF triggers a variety of pathological reactions including tumor neo-angiogenesis. Several groups have demonstrated that inhibiting PAF-PAF receptor pathway at the level of a ligand or receptor results in an effective inhibition of experimental tumor growth and metastasis. In particular, our group has recently demonstrated that PAF receptor antagonists can effectively inhibit the metastatic potential of human melanoma cells in nude mice. Furthermore, we showed that PAF stimulated the phosphorylation of CREB and ATF-1 in metastatic melanoma cells, which resulted in overexpression of MMP-2 and MT1-MMP. Our data indicate that PAF acts as a promoter of melanoma metastasis in vivo. Since only metastatic melanoma cells overexpress CREB/ATF-1, we propose that these cells are better equipped to respond to PAF within the tumor microenvironment when compared to their non-metastatic counterparts. PMID- 17721745 TI - Evolution of robotic surgery in the treatment of localized prostate cancer. AB - Adenocarcinoma of the prostate is the second most common cancer in men in the United States (following only skin cancer) and accounts for 33% of all newly diagnosed male cancers. It is estimated that in 2007, 218,890 men will be diagnosed with prostate cancer and 27,050 will die from this disease. While most currently diagnosed prostate cancers are localized, radical prostatectomy remains a gold standard treatment. Since its original description, radical retropubic prostatectomy has evolved over the last three decades to a precise, sophisticated procedure with minimal mortality, and excellent surgical outcomes. However, despite its efficacy, open surgical treatment is inherently associated with blood loss and significant pain. Due to these reasons, many men have sought other, less invasive forms of treatment. With its development in the late 1990s, minimally invasive surgery has significantly and irrevocably changed the surgical treatment of prostate cancer. Robotic-assisted technology has further propelled the utilization of the laparoscopic approach for radical prostatectomy, particularly for non-laparoscopic trained surgeons. The implementation of robotic technology has been rapid. Presently, 7 years after its approval by the FDA, many hospitals have established for robotic-assisted radical prostatectomy programs. This trend will undoubtedly continue to grow as more surgeons become familiar with the procedure, more robotic systems become available, and increasingly mature data is published. Robotic-assisted laparoscopic radical prostatectomy allows patients the benefits of minimally invasive surgery with functional and oncological results comparable to those from open and standard laparoscopic procedures, we believe that this surgical approach will shortly evolve into the standard surgical approach for localized prostate cancer. PMID- 17721746 TI - Initial Therapy of Multiple Myeloma in Patients who are Candidates for Stem Cell Transplantation. AB - Multiple myeloma (MM), a B cell hematologic malignancy involving plasma cells, responds to a variety of drugs including alkylators, steroids, anthracyclines, immunomodulators and proteosome inhibitors. The disease, however, remains largely incurable for the majority of patients. For patients who are suitable candidates, high dose chemotherapy with autologous stem cell support (ASCT) after induction therapy has been shown to improve response rates, progression free survival and overall survival compared to conventional chemotherapy. The availability of new drugs including thalidomide, lenalidomide and bortezomib has rapidly changed induction strategies. These drugs have been combined with corticosteroids, alkylators and anthracyclines to treat front-line patients with MM. Preliminary, phase 1-2 studies have indicated very high response rates and complete response rates formerly only seen with ASCT. Emerging data from randomized trials suggest that older regimens such as vincristine, adriamycin and dexamethasone (VAD) are not as effective for induction as newer combinations. Thus new regimens incorporating novel agents should improve overall response rates, increase complete responders which should translate into improved progression free and overall survival. PMID- 17721744 TI - Downstream promoter sequence of an Indian isolate of Rice tungro bacilliform virus alters tissue-specific expression in host rice and acts differentially in heterologous system. AB - An Indian isolate of Rice tungro bacilliform virus from West Bengal (RTBV-WB) showed significant nucleotide differences in its putative promoter region when compared with a previously characterized isolate from Philippines. The transcription start site of RTBV-WB was mapped followed by assessing the activity and tissue-specificity of the full-length (FL) promoter (-231 to +645) and several of its upstream and downstream deletions by studying the expression of beta-Glucuronidase (GUS) reporter gene in transgenic rice (Oryza sativa L. subsp. indica) plants at various stages of development. In addition to the expected vascular-specific expression pattern, studied by histochemical staining, GUS enzymatic assay and northern and RT-PCR analysis, two novel patterns were revealed in some of the downstream deleted versions; a non-expressing type, representing no expression at any stage in any tissue and constitutive type, representing constitutive expression at all stages in most tissues. This indicated the presence of previously unreported positive and negative cis regulatory elements in the downstream region. The negative element and a putative enhancer region in the upstream region specifically bound to rice nuclear proteins in vitro. The FL and its deletion derivatives were also active in heterologous systems like tobacco (Nicotiana tabacum) and wheat (Triticum durum). Expression patterns in tobacco were different from those observed in rice suggesting the importance of upstream elements in those systems and host-specific regulation of the promoter in diverse organisms. Thus, the RTBV-WB FL promoter and its derivatives contain an array of cis-elements, which control constitutive or tissue- and development-specific gene expression in a combinatorial fashion. PMID- 17721747 TI - Serum uric acid shows a J-shaped trend with coronary mortality in non-insulin dependent diabetic elderly people. The CArdiovascular STudy in the ELderly (CASTEL). AB - The relationship between serum uric acid (SUA) and risk of coronary heart disease (CHD) mortality remains controversial, particularly in diabetic subjects. The aim of the present study is to evaluate whether SUA independently predicts CHD mortality in non-insulin-dependent elderly people from the general population and to investigate the interactions between SUA and other risk factors. Five hundred and eighty-one subjects aged >/=65 years with non-insulin-dependent diabetes mellitus were prospectively studied in the frame of the CArdiovascular STudy in the ELderly (CASTEL). Historical and clinical data, blood tests and 12-year fatal events were recorded. SUA as a continuous item was divided into tertiles and, for each tertile, adjusted relative risk (RR) with 95% confidence intervals (CI) was derived from multivariate Cox analysis. CHD mortality was predicted by SUA in a J shaped manner. Mortality rate was 7.9% (RR 1.28, CI 1.05-1.72), 6.0% (reference tertile) and 12.1% (RR 1.76, CI 1.18-2.27) in the increasing tertiles of SUA, respectively, without any difference between genders. In diabetic elderly subjects, SUA independently predicts the risk of CHD mortality in a J-shaped manner. PMID- 17721748 TI - Maternal-foetal status of copper, iron, molybdenum, selenium and zinc in obese gestational diabetic pregnancies. AB - Obesity is well known to be a contributory risk factor for several disease states, including diabetes mellitus. Paucity of data on maternal-foetal status of essential trace elements in obese diabetic pregnancies prompted us to undertake this study. Maternal venous and umbilical arterial and venous blood samples were collected from obese gestational diabetic patients (Body Mass Index (BMI) >30) and control obese pregnant women (BMI>30) at time of spontaneous delivery or caesarean sections and concentrations of essential trace elements such as Cu, Fe, Mo, Se and Zn were determined in various samples by atomic absorption spectrophotometry. Activities of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPX) and total antioxidant (TAO) in maternal and umbilical blood were assessed using appropriate reagent kits. Maternal-foetal disposition and exchange parameters of elements studied were assessed using established criteria. Concentrations of Cu, Fe, Mo, Se and Zn in serum of control obese pregnant women (n=10) averaged 2404, 2663, 11.0, 89.0 and 666 microg/l respectively, while in the obese diabetic group (n=11), the corresponding values averaged 2441, 2580, 13.3, 85.1 and 610 microg/l respectively. Activities of antioxidant enzymes such as SOD, GPX and TAO were not significantly different in maternal veins of control and diabetic groups. Varying differences were noted in the case of antioxidant enzyme activities in umbilical blood samples of control and study groups. We conclude that obesity is not associated with significant alterations in antioxidant enzyme status in gestational diabetes and only with relatively minor alterations in status of some essential trace elements. PMID- 17721749 TI - Impact of fasting and postprandial state on plasma carnitine concentrations during aerobic exercise in type 2 diabetes. AB - The effects of metabolic states of fasting and post-absorption on plasma concentrations of free carnitine (FC), acylcarnitine (AC) and total carnitine (TC) were compared during submaximal exercise in subjects with type 2 diabetes mellitus. Ten sedentary men (54+/-5 years) treated with oral hypoglycaemic agents were tested on two separate occasions: following an overnight fast and 2 h after a 395-kcal standardised breakfast. Exercise was performed at 60% of [Formula: see text]O(2peak) on a cycle ergometer for 60 min. Blood samples were drawn at rest for baseline values and following 60 min of exercise and 30 min of recovery. Our results show that: (1) baseline levels of TC, FC and AC were similar in fasted and postprandial groups, (2) TC and AC levels were increased during exercise in the fasted group only, (3) FC levels were decreased during exercise in both fasted and postprandial state and (4) the AC/FC ratio increased during exercise in the fasted group. Our results indicate that the metabolic state of the diabetic patient is associated with a different plasma carnitine status. These patterns may reflect differences in energy metabolism associated with fasting and postprandial hyperglycaemia. PMID- 17721750 TI - Soybean oil treatment impairs glucose-stimulated insulin secretion and changes fatty acid composition of normal and diabetic islets. AB - We investigated the effect of sub-chronic soybean oil (SO) treatment on the insulin secretion and fatty acid composition of islets of Langerhans obtained from Goto-Kakizaki (GK), a model of type 2 diabetes, and normal Wistar rats. We observed that soybean-treated Wistar rats present insulin resistance and defective islet insulin secretion when compared with untreated Wistar rats. The decrease in insulin secretion occurred at all concentrations of glucose and arginine tested. Furthermore we observed that soybean-treated normal islets present a significant decrease in two saturated fatty acids, myristic and heneicosanoic acids, and one monounsaturated eicosenoic acid, and the appearance of the monounsaturated erucic acid. Concerning diabetic animals, we observed that soybean-treated diabetic rats, when compared with untreated GK rats, present an increase in plasma non-fasting free fatty acids, an exacerbation of islet insulin secretion impairment in all conditions tested and a significant decrease in the monounsaturated palmitoleic acid. Altogether our results show that SO treatment results in a decrease of insulin secretion and alterations on fatty acid composition in normal and diabetic islets. Furthermore, the impairment of insulin secretion, islet erucic acid and fasting plasma insulin levels are similar in treated normal and untreated diabetic rats, suggesting that SO could have a deleterious effect on beta-cell function and insulin sensitivity. PMID- 17721751 TI - The association of early atherosclerosis and retinopathy in adolescents with type 1 diabetes: preliminary report. AB - Recent studies have shown a close correlation between advanced diabetic retinopathy and the late stages of atherosclerosis. The purpose of this study was to analyse the association between diabetic retinopathy and early atherosclerotic changes in adolescents with type 1 diabetes. We studied 28 adolescents with type 1 diabetes. Eight patients with nonproliferative retinopathy were compared with the remaining 20 patients, and with 11 healthy controls. The function of endothelium was assessed by measuring flow-mediated dilatation (FMD), the intima media thickness (IMT) of the common carotid arteries and adhesion molecules (sICAM-1, sVCAM-1, sE-selectin). In the group with retinopathy FMD equalled 7.8+/ 4.1% vs. 12.1+/-5.1% in the control group (p=0.04), and in the group without retinopathy, 7.6+/-5.5% (p=0.04 compared to controls). Higher IMT was found in all patients with diabetes in comparison with healthy controls: 0.49+/-0.06 mm vs. 0.42+/-0.03 mm (p=0.001). Patients with retinopathy had a significantly higher value of IMT in comparison not only with controls but also with patients without complications: 0.56+/-0.06 mm vs. 0.47+/-0.03 mm (p=0.0001). Adhesion molecule levels were not changed in patients with retinopathy. Higher IMT was found in adolescents with diabetic retinopathy in comparison with patients without complications, which may suggest that macrovascular changes are more advanced in these patients than in their diabetic peers without retinopathy. PMID- 17721752 TI - Prediction of all-cause mortality in a patient population with hypertension and type 2 DM by using traditional risk factors and serum-phosphate,-calcium and magnesium. AB - The aim of this study is to investigate whether the prediction of all-cause mortality from traditional risk factors is improved by adding electrolytes (serum phosphate (S-P), serum-calcium (S-Ca) and serum-magnesium (S-Mg)) in a Cox regression. The study uses an 18-year follow-up of patients (n=2504) referred by physicians in primary health care and hospitals to the Vindeln Patient Education (VPE) Center, mainly with a diagnosis of hypertension (HT), type 2 diabetes mellitus (DM) and/or obesity. Cox regression, with the latest registered value and baseline values for risk factors, was used to study all-cause mortality in men and women. 221 out of 1096 men and 157 out of 1408 women died during the 18 year follow-up (20% and 11% respectively). The Cox regression analysis reveals that high blood glucose (B-Glu) and low S-Mg were significantly associated with increased all-cause mortality in the whole patient population as well as in men and women separately. Among women, type 2 DM and systolic blood pressure (SBP) and among men, high S-Ca, S-P, S-urate and body mass index (BMI) were the main predictors of all-cause mortality. There is significantly improved prediction of all-cause mortality with electrolytes added to the traditional risk factors. High B-Glu and low S-Mg in both men and women, and high S-Ca and S-P in men, are significantly associated with all-cause mortality. The metabolic disturbance in this high-risk group of patients can be more fully understood if ionic imbalance is included in the prediction of mortatlity. PMID- 17721753 TI - A pharmacoeconomical model for choice of a treatment for pregnant women with gestational diabetes. AB - This study discusses two main questions: the direct medical costs and the clinical effectiveness of the hospital treatment with insulin of pregnant women with gestational diabetes (GD). A prospective study that includes 50 women with GD is performed. The pregnant women are divided into 2 groups: Group I (n=30) - pregnant women treated only with a diet; and Group II (n=20) - pregnant women treated with diet and insulin. We found that the metabolite compensation degree is improved after the applied treatment with insulin. The coefficient cost/effectiveness is 6954 lv./100 women. The analysis decision tree confirms in a very convenient way the fact that insulin treatment is a clinically more effective and financially more profitable strategy. PMID- 17721754 TI - Effects of rosiglitazone on plasma brain natriuretic peptide levels and myocardial performance index in patients with type 2 diabetes mellitus. AB - Thiazolidinediones (TZD) have become a powerful tool for lowering insulin resistance. The problem of cardiovascular adverse events including fluid retention and risk of heart failure should be well known and recognised. We aimed to evaluate the long-term effects of rosiglitazone on cardiac function and fluid dynamics. Forty-six type 2 diabetic patients were randomised to treatment with rosiglitazone or metformin or to a control group. There are no significant differences between the groups in the duration of diabetes, HbA1c, plasma brain natriuretic peptide (BNP) levels, body mass index and myocardial performance indexes (MPIs) before the treatment. After three and six months all these parameters were repeated. Rosiglitazone increased plasma BNP levels and worsened MPIs 3 months after the start of treatment. Also left ventricular end-systolic volume increased and weight gain was observed. But these results were statistically non-significant (all p>0.05). When we continued rosiglitazone treatment to six months the increase in BNP levels became soft and statistically significant improvements were seen in MPIs (p<0.01). Also left ventricular end systolic volume decreased significantly (p=0.004) and weight gain was stopped. In patients with type 2 diabetes, TZD treatment might have slight adverse effects on ventricular contractility and fluid dynamics at the beginning of the therapy. However, these changes seem to stabilise in the long term. PMID- 17721755 TI - Induction of hyperglycaemia in zebrafish (Danio rerio) leads to morphological changes in the retina. AB - Diabetes affects over 16 million Americans yearly, resulting in hyperglycaemia and microvascular complications, including retinopathy, neuropathy and nephropathy. Animal models have been developed to examine the immunological aspects of type 1 diabetes and the pathogenic mechanisms associated with diabetic retinopathy, but the methods of diabetes induction raise concerns regarding these models. Zebrafish (Danio rerio) have been used extensively to study developmental processes and mutant zebrafish strains have been used to examine vision disease present in humans. In this paper, we have induced hyperglycaemia in zebrafish by alternately immersing the fish in glucose solution or water. Eyes from untreated fish or fish exposed to alternating glucose/water solutions for 28 days were dissected, sectioned and stained to visualise cell bodies in the retina. In untreated fish retinas, the inner plexiform layer (IPL) and inner nuclear layer (INL) were approximately the same thickness, whereas in fish repeatedly exposed to glucose solutions the IPL was approximately 55% the thickness of the INL. Both the IPL and INL were significantly reduced in retinas of treated fish, compared to untreated fish, similar to that seen in other animal models of diabetes and in diabetic patients. These results suggest that zebrafish may be used as an animal model in which to study diabetic retinopathy. PMID- 17721756 TI - Normal fasting plasma glucose levels and type 2 diabetes: the high-risk and population strategy for occupational health promotion (HIPOP-OHP) [corrected] study. AB - The objective of this study is to ascertain if higher normal fasting glucose levels are also an independent risk of developing diabetes in an Asian population, and we thus analysed data from a cohort of healthy Japanese workers. We used data from the non-randomised trial on health promotion intervention, High risk and Population Strategy for Occupational Health Promotion (HIPOP-OHP) Study. Diabetes cases and those who had fasting blood glucose levels equal to or greater than 100 mg/dl at baseline were excluded, and the Cox proportional-hazards model was used for the analysis. During the four-year follow-up of 2212 participants, we found 37 diabetes cases. In the multivariable model, people with blood glucose levels in the 4th quartile had a higher risk of diabetes than those in the bottom quartile; the multivariable-adjusted odds ratio was 2.52. The risk of diabetes abruptly rose in persons with blood glucose levels higher than 94 mg/dl (fourth quartile). A significant linear trend was not observed in the 1st to 3rd quartiles (p=0.726). In conclusion, higher fasting glucose level was associated with the risk of diabetes, and we found a threshold in the association between fasting blood glucose levels and risk of diabetes in an Asian population. PMID- 17721757 TI - A case of pegylated interferon alpha-related diabetic ketoacidosis: can this complication be avoided? AB - We report the case of a 42-year-old woman with chronic hepatitis C (genotype 1), who in June 2004 started therapy with pegylated interferon alpha (PEG-IFNalpha) plus ribavirin. Two months later, she discontinued treatment because of polydipsia, polyuria and vomiting leading to a marked dehydration. Biochemical data showed type 1 diabetes mellitus with ketoacidosis, and insulin therapy was started. The patient, who before starting PEG-IFN alpha plus ribavirin therapy tested negative for glutamic acid decarboxylase antibodies (GADAb) and islet cell (ICAb) antibodies, became strongly positive for both autoimmune markers. This case confirms that patients with chronic hepatitis C who do not have baseline markers of pancreatic autoimmunity may develop severe ketoacidosis during treatment with PEG-IFNalpha, as well as with standard IFNalpha. In order to avoid this complication, as no guidelines are available and the pancreatic autoimmunity markers are not routinely analysed, we suggest frequent monitoring (e.g., every one to two weeks) of glycaemic values: e.g., every one to two weeks during the first 3 months (when this complication occurs most frequently) and monthly thereafter so as to identify diabetes at an early stage and before the onset of the appearance of severe ketoacidosis, which is life-threatening. PMID- 17721758 TI - Continuous subgaleal suction drainage for the treatment of chronic subdural haematoma. PMID- 17721762 TI - A question of survival? Interaction between probiotics and the gastrointestinal tract. PMID- 17721763 TI - [Why are there analogous disease mechanisms in chronic inflammatory diseases?]. PMID- 17721764 TI - Tinea incognito due to Microsporum canis in a 76-year-old woman. PMID- 17721765 TI - Are probiotics detectable in human feces after oral uptake by healthy volunteers? AB - GOALS: Assessment of the presence of probiotic bacteria in feces after oral ingestion. BACKGROUND: Probiotic bacteria are said to have beneficial effects on the host. As a precondition for any effect, probiotic strains must survive passage through the gastrointestinal tract. STUDY: The feces of seven volunteers were analyzed for the presence of probiotic strains after one week's oral ingestion of each of six commercially available products: E. coli Nissle 0.5-5 x 10(9) cells (Mutaflor), Enterococcus faecium SF 68 7.5 x 10(7) cells (Bioflorin), Lactobacillus acidophilus and Bifidobacterium infantis both 1 x 10(9) cells (Infloran), Lactobacillus gasseri and Bifidobacterium longum both 1 x 10(8) cells (Omniflora), Lactobacillus casei rhamnosus 1 x 10(9) cells (Antibiophilus), and yoghurt enriched with Lactobacillus casei Immunitas 1 x 10(10) cells (Actimel). Ten colonies were selected from each stool sample, and DNA was extracted and typed using random amplification of polymorphic DNA (RAPD). Typing patterns of the ingested probiotics and the fecal isolates were compared. RESULTS: Fingerprints identical to the ingested probiotic strains were recovered from fecal samples of 4/7 volunteers after one week of Mutaflor, from 4/6 after taking Bioflorin, and from 1/6 after Infloran. Cultivation of strains of the same species from fecal specimens was negative after consumption of Antibiophilus, Omniflora and Actimel. CONCLUSIONS: After oral consumption of probiotics, E. coli and enterococci could be detected in stool samples (57% and 67%, respectively). In contrast, with only one exception, ingested lactobacilli and bifidobacteria could not be detected in human feces. PMID- 17721766 TI - Genetics of suicide: a systematic review of twin studies. AB - OBJECTIVES: Convergent evidence from a multitude of research designs (adoption, family, genomescan, geographical, immigrant, molecular genetic, surname, and twin studies of suicide) suggests genetic contributions to suicide risk. The present account provides a comprehensive and up-to-date review of the twin studies on this topic. METHODS: A total of 32 studies (19 case reports, 5 twin register based studies, 4 population-based epidemiological studies, 4 studies of surviving co-twins) located through extensive literature search strategies are summarized and discussed here. This literature corpus was published between 1812 and 2006 in six languages and reports data from 13 countries. RESULTS: A meta-analysis of all register-based studies and all case reports aggregated shows that concordance for completed suicide is significantly more frequent among monozygotic than dizygotic twin pairs. The results of co-twin studies rule out exclusively psychosocially based explanations of this pattern. Population-based epidemiological studies demonstrate a significant contribution of additive genetic factors (heritability estimates: 30-55%) to the broader phenotype of suicidal behavior (suicide thoughts, plans and attempts) that largely overlaps for different types of suicidal behavior and is largely independent of the inheritance of psychiatric disorders. Nonshared environmental effects (i.e. personal experiences) also contribute substantially to the risk of suicidal behavior, whereas effects of shared (family) environment do not. CONCLUSIONS: The totality of evidence from twin studies of suicide strongly suggests genetic contributions to liability for suicidal behavior. To further research progress in this area, an extensive discussion of design limitations, shortcomings of the literature and further points is provided, including sources of bias, gaps in the literature, errors in previous reviews, age and sex effects and twin-singleton differences in suicide risk, and notes from a history-of-science view. PMID- 17721767 TI - Lipoprotein lipase HindIII polymorphism influences HDL-cholesterol levels in statin-treated patients with coronary artery disease. AB - BACKGROUND: HDL-cholesterol (HDL-C) is a recognized athero-protective factor and low levels of HDL-C occur frequently in patients with coronary artery disease. Regulation of HDL-C level most probably results from the interaction of genes involved in lipoprotein metabolism and also from non-genetic factors. We studied associations and interactions among HindIII polymorphisms of the lipoprotein lipase gene LPL and selected non-genetic factors with respect to HDL-C levels in patients with coronary artery disease. PATIENTS AND METHODS: 288 Slovak patients (35% women) with documented coronary artery disease, age (mean +/- SEM) 60 +/- 1 years and BMI 29 +/- 0.3 kg/m(2), were examined and genotyped for LPL HindIII (rs320) using a PCR/RFLP method. HDL-C levels were determined in a direct enzymatic assay. RESULTS: In the sample overall there were no significant differences across the LPL genotypes in adjusted HDL-C levels or in other lipids, although a trend toward higher HDL-C and lower triglycerides in H-H- homozygotes was observed. Multiple linear regression identified a significant interaction between LPL HindIII and statin treatment, which together with sex and diabetes explained 12.1% of HDL-C variance. Accordingly, in statin-treated patients we observed significant stepwise increments of the HDL-C level related to the increasing number of H- alleles (P = 0.04 for linear trend), whereas no such association was observed in patients without hypolipidemic treatment. H-H- homozygotes had a 16% (0.19 mmol/l) higher level of HDL-C than the H+H+ homozygotes (P = 0.06). CONCLUSION: HDL-C may be influenced by an interaction between statin treatment and LPL HindIII genotype. However, the effect of this interaction appears to be small when compared with the effect of non-genetic factors. This finding requires replication in a pharmacogenetic study. PMID- 17721768 TI - Impaired vascular nitric oxide bioactivity in women with previous gestational diabetes. AB - BACKGROUND: Dysfunction of the vascular endothelium, preceding vascular morbidity and type 2 diabetes, is present in women with previous gestational diabetes (GDM). However, it is unknown whether excess weight, insulin resistance, and asymmetric dimethylarginine (ADMA)--an endogenous nitric oxide (NO) synthase inhibitor--also contribute to the vascular changes observed in these patients. The aim of this study was therefore to identify factors other than GDM that impair vascular function. METHODS: Seven overweight and five non-overweight women with previous GDM were included in this study. Vascular function was assessed from forearm blood-flow responses to the endothelium-dependent vasodilator acetylcholine (ACh), the endothelium-independent vasodilator glyceryltrinitrate, the vasoconstrictor norepinephrine and the NO synthase inhibitor N(G)-monomethyl L-arginine (L-NMMA). ADMA was measured in venous blood, and insulin resistance was estimated from a modified intravenous glucose tolerance test. Twenty healthy male volunteers served as a historical control group. RESULTS: Vasodilation of forearm resistance vessels in response to ACh was impaired in overweight women when compared with non-overweight women (P < 0.05); similarly, vasoconstrictor reactivity tended to be smaller in the overweight group. In addition, there was a significant relationship between vascular responsiveness to ACh and L-NMMA, body mass index, serum ADMA concentrations and stimulated glucose levels (all P < 0.05). ACh responses and ADMA levels in non-overweight women were similar to those of healthy controls. CONCLUSION: Factors such as obesity, increased ADMA levels and insulin resistance appear to be strong contributors to endothelial dysfunction observed in women with GDM. PMID- 17721769 TI - Predictive values of cranial ultrasound and assessment of general movements for neurological development of preterm infants in the Maribor region of Slovenia. AB - OBJECTIVE: The aim of the study was to assess the predictive values of cranial ultrasound (US) scans and assessment of general movements of fidgety character (GMs) for the later neurological development of preterm infants in the Maribor region of Slovenia. METHODS: Results of cranial US scans done longitudinally from the day of birth until the end of three months of chronologic age and results of GMs at three months of corrected age were compared with traditional neurological examination and evaluation of psychomotor development of the same children at the corrected age of six years. RESULTS: A total of 112 preterm infants (gestational age 37 weeks and below) were included in the study. The infants were classified as low-risk or high-risk for neurological impairment on the basis of cranial US scans. The scans classified as low-risk were followed by a normal neurological outcome in 74 (89%) of 83 infants; those classified as high-risk for neurological impairment were followed by abnormal neurological outcome in 21 (72%) of 29 infants. Of 77 infants with normal fidgety movements, 73 (95%) had a normal neurological outcome and 4 (5%) had an abnormal neurological outcome; of 35 infants with abnormal or absent fidgety movements, 26 (74%) had an abnormal neurological outcome and 9 (26%) had a normal neurological outcome. Of 30 children with abnormal outcome, cerebral palsy was diagnosed in 16, mental retardation in one, nine children had both of these, and four had complex minor neurological dysfunction. The validity of the scans was 85%, sensitivity 70%, specificity 90%, positive predictive value 72% and negative predictive value 89%; the validity of the GMs was 88%, sensitivity 87%, specificity 89%, positive predictive value 74% and negative predictive value 95%. CONCLUSIONS: The sensitivity of the cranial US scans was clearly lower than that of assessment of general movements of a fidgety character. The specificities of the two methods were almost the same. PMID- 17721772 TI - [Attention and executive functions in patients with severe obesity]. PMID- 17721770 TI - A rare cause of breast mass that mimics carcinoma: Foreign body reaction to amorphous surgical material. AB - A breast mass caused by foreign body type granulomatous reaction to surgical material is a very rare lesion and may mimic carcinoma. Reported foreign materials have included suture materials, silicone, paraffin, gunpowder and carbon particles used for localization of a nonpalpable breast lesions. To our knowledge, a foreign body reaction to gauze sponge has not been reported previously. A 58-year-old woman who had an enlarging mass that mimicked breast carcinoma, due to foreign body reaction to gauze sponge is presented here, and relevant literature is reviewed. PMID- 17721775 TI - Comment on "Chest physiotherapy prolongs duration of ventilation in the critically ill ventilated for more than 48 hours" by Drs. Templeton and Palazzo. PMID- 17721773 TI - Effects of starch synthase IIa gene dosage on grain, protein and starch in endosperm of wheat. AB - Starch synthases (SS) are responsible for elongating the alpha-1,4 glucan chains of starch. A doubled haploid population was generated by crossing a line of wheat, which lacks functional ssIIa genes on each genome (abd), and an Australian wheat cultivar, Sunco, with wild type ssIIa alleles on each genome (ABD). Evidence has been presented previously indicating that the SGP-1 (starch granule protein-1) proteins present in the starch granule in wheat are products of the ssIIa genes. Analysis of 100 progeny lines demonstrated co-segregation of the ssIIa alleles from the three genomes with the SGP-1 proteins, providing further evidence that the SGP-1 proteins are the products of the ssIIa genes. From the progeny lines, 40 doubled haploid lines representing the eight possible genotypes for SSIIa (ABD, aBD, AbD, ABd, abD, aBd, Abd, abd) were characterized for their grain weight, protein content, total starch content and starch properties. For some properties (chain length distribution, pasting properties, swelling power, and gelatinization properties), a progressive change was observed across the four classes of genotypes (wild type, single nulls, double nulls and triple nulls). However, for other grain properties (seed weight and protein content) and starch properties (total starch content, granule morphology and crystallinity, granule size distribution, amylose content, amylose-lipid dissociation properties), a statistically significant change only occurred for the triple nulls, indicating that all three genes had to be missing or inactive for a change to occur. These results illustrate the importance of SSIIa in controlling grain and starch properties and the importance of amylopectin fine structure in controlling starch granule properties in wheat. PMID- 17721776 TI - Double bundle or single bundle plus an extra articular tenodesis? PMID- 17721777 TI - Measurement of the graft angles for the anterior cruciate ligament reconstruction with transtibial technique using postoperative magnetic resonance imaging in comparative study. AB - The aims of this study were to quantify the angle and placement of an anterior cruciate ligament (ACL) grafted with a single incision ACL reconstruction technique using postoperative magnetic resonance imaging (MRI), and to compare the results with those with a native ACL. Between February 1996 and May 2004, 96 consecutive patients, who had undergone postoperative MRI of the knee followed by an arthroscopically assisted ACL reconstruction with either a hamstring tendon or bone-patellar tendon-bone (BTB) autograft, were enrolled in this study. The femoral tunnel was drilled using the transtibial technique. The patients were divided into two groups; the hamstring tendon graft group (group H; 50 patients) and the BTB graft group (group B; 46 patients). All the patients including both groups in this study underwent postoperative MRI and were followed up for a minimum of 2 years. The control group (group C) consisted of 50 patients whose meniscus tear had been operated on by arthroscopy and whose ACL was intact. The orientation of the ACL ligament or graft was measured using three different methods: the sagittal ACL angle, the ACL-Blumensaat line angle, and the coronal ACL angle. The mean sagittal ACL angle in group C (58.7 +/- 3.8 degrees ) was significantly lower than in groups H (64.6 +/- 4.2 degrees ) and B (71.3 +/- 6.0 degrees ). The mean ACL-Blumensaat line angle in group C (8.6 +/- 3.6 degrees ) was also significantly lower than in groups H (12.8 +/- 5.2 degrees ) and B (18.0 +/- 5.3 degrees ). The mean coronal ACL angle in group C (65.9 +/- 4.4 degrees ) was lower than that in groups H (73.5 +/- 2.4 degrees ) and B (75.2 +/- 2.9 degrees ). The grafted ACL of the hamstring tendon and BTB grafts on the postoperative MRI showed a significant vertical angle in the coronal and sagittal plane compared with the native ACL. In the sagittal plane, the hamstring tendon graft was positioned more obliquely than the BTB graft, which had a larger angle of the tibial tunnel, in an attempt to prevent a graft-tunnel mismatch. The postoperative MRI study showed that the more horizontally the angle of the tibial tunnel can be placed in a single incision ACL reconstruction, the more efficiently it can produce a graft closer to the native ACL. PMID- 17721778 TI - Clinical comparison of the autologous quadriceps tendon (BQT) and the autologous patella tendon (BPTB) for the reconstruction of the anterior cruciate ligament. AB - The use of the BPTB-autograft is a very common method for ACL reconstruction. Nevertheless, the problem of the typical donor-site-morbidity is unresolved. Recently, a transplant of quadriceps tendon, with an attached bone block (BQT) has been increasingly relied upon. The purpose of this study was to examine the clinical results of a group of patients after arthroscopic ACL reconstruction using either BPTB or quadriceps tendon autograft after a minimum follow-up of 2 years in terms of knee joint stability and function using both subjective and objective criteria. Retrospective study. A total of 260 patients with ACL ruptures were operated between 1995 and 2000; 124 received a BQT-autograft, including 8 revisions; 136 patients received a BPTB-autograft, exclusively primary interventions. The results were evaluated using the IKDC-, Noyes- and Lysholm-Scores. It was possible to re-evaluate 194 patients after a minimum follow-up period of 2 years, 64 of 260 patients (25%) were lost to follow-up. Ninety-seven percent of the operated knee joints in the BPTB-group were judged as normal or almost normal with the IKDC evaluation, as were 83% in the BQT-group (P < or = 0.001). The BQT-group showed a significantly better result in the evaluation of the donor-site-morbidity. We found no significant differences in the functional outcome according to the Lysholm- and Noyes-Score. In comparison to the results after using a BQT-transplant for reconstruction of a ruptured ACL the use of the BPTB-transplant is in favour concerning patient satisfaction and IKDC evaluation. For patients with activities involving kneeling or prolonged flexion of the knee joint BQT-transplants can be a good alternative, however. PMID- 17721779 TI - Selection of micronutrients used along with DMSA in the treatment of moderately lead intoxicated mice. AB - The objective of this study was to explore the optimum combination of micronutrients used with 2,3-dimercaptosuccinic acid (DMSA) in the treatment of moderately lead-intoxicated mice. Experiment was carried out based on the orthogonal design L(8)(2(7)) setting six factors with two different levels of each, and eight groups of mice were needed. Mice were exposed to lead by drinking water contaminated with 0.1% lead acetate for four consecutive weeks, and then supplemented by gavage with different combinations of micronutrients with and without DMSA as designed in the orthogonal table. Lead levels in blood, liver, kidney, brain and bone and activities of blood delta-aminolevulinic acid dehydratase (ALAD) were analyzed after cessation of supplementation. The results suggested that DMSA was the only factor which could decrease significantly lead levels in blood, liver, kidney and bone; calcium and ascorbic acid were the notable factors decreasing lead levels in blood, liver, kidney, bone and brain; zinc and calcium were the notable factors reversing the lead-inhibited activities of blood ALAD; taurine was the notable factor decreasing lead levels in kidney and brain; and thiamine was the notable factor decreasing lead levels in brain. The lowest lead level in blood, liver, kidney and bone was shown in the mice supplemented with combination of calcium and ascorbic acid along with DMSA. In conclusion, the optimum combination of micronutrients used with DMSA suggested in present study was calcium and ascorbic acid, which seemed to potentiate the chelating efficacy of DMSA in the treatment of moderately lead intoxicated mice. PMID- 17721780 TI - Human volunteer study on the inhalational and dermal absorption of N-methyl-2 pyrrolidone (NMP) from the vapour phase. AB - N-Methyl-2-pyrrolidone (NMP) is a versatile organic solvent frequently used for surface cleaning such as paint stripping or graffiti removal. Liquid NMP is rapidly absorbed through the skin but dermal vapour phase absorption might also play an important role for the uptake of the solvent. This particular aspect was investigated in an experimental study with 16 volunteers exposed to 80 mg/m(3) NMP for 8 h under either whole-body, i.e. inhalational plus dermal, or dermal only conditions. Additionally, the influence of moderate physical workload on the uptake of NMP was studied. The urinary concentrations of NMP and its metabolites 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methylsuccinimide (2 HMSI) were followed for 48 h and analysed by gas chromatography-mass spectrometry (GC-MS). Percutaneous uptake delayed the elimination peak times and the apparent biological half-lives of NMP and 5-HNMP. Under resting conditions, dermal-only exposure resulted in the elimination of 71 +/- 8 mg NMP equivalents as compared to 169 +/- 15 mg for whole-body exposure. Moderate workload yielded 79 +/- 8 mg NMP (dermal-only) and 238 +/- 18 mg (whole-body). Thus, dermal absorption from the vapour phase may contribute significantly to the total uptake of NMP, e.g. from workplace atmospheres. As the concentration of airborne NMP does not reflect the body dose, biomonitoring should be carried out for surveillance purposes. PMID- 17721782 TI - Toward the harmonization of immune monitoring in clinical trials: quo vadis? PMID- 17721781 TI - Results and harmonization guidelines from two large-scale international Elispot proficiency panels conducted by the Cancer Vaccine Consortium (CVC/SVI). AB - The Cancer Vaccine Consortium of the Sabin Vaccine Institute (CVC/SVI) is conducting an ongoing large-scale immune monitoring harmonization program through its members and affiliated associations. This effort was brought to life as an external validation program by conducting an international Elispot proficiency panel with 36 laboratories in 2005, and was followed by a second panel with 29 participating laboratories in 2006 allowing for application of learnings from the first panel. Critical protocol choices, as well as standardization and validation practices among laboratories were assessed through detailed surveys. Although panel participants had to follow general guidelines in order to allow comparison of results, each laboratory was able to use its own protocols, materials and reagents. The second panel recorded an overall significantly improved performance, as measured by the ability to detect all predefined responses correctly. Protocol choices and laboratory practices, which can have a dramatic effect on the overall assay outcome, were identified and lead to the following recommendations: (A) Establish a laboratory SOP for Elispot testing procedures including (A1) a counting method for apoptotic cells for determining adequate cell dilution for plating, and (A2) overnight rest of cells prior to plating and incubation, (B) Use only pre-tested serum optimized for low background: high signal ratio, (C) Establish a laboratory SOP for plate reading including (C1) human auditing during the reading process and (C2) adequate adjustments for technical artifacts, and (D) Only allow trained personnel, which is certified per laboratory SOPs to conduct assays. Recommendations described under (A) were found to make a statistically significant difference in assay performance, while the remaining recommendations are based on practical experiences confirmed by the panel results, which could not be statistically tested. These results provide initial harmonization guidelines to optimize Elispot assay performance to the immunotherapy community. Further optimization is in process with ongoing panels. PMID- 17721783 TI - The CIMT-monitoring panel: a two-step approach to harmonize the enumeration of antigen-specific CD8+ T lymphocytes by structural and functional assays. AB - The interpretation of the results obtained from immunomonitoring of clinical trials is a difficult task due to the variety of methods and protocols available to detect vaccine-specific T-cell responses. This heterogeneity as well as the lack of standards has led to significant scepticism towards published results. In February 2005, a working group was therefore founded under the aegis of the Association for Immunotherapy of Cancer ("CIMT") in order to compare techniques and protocols applied for the enumeration of antigen-specific T-cell responses. Here we present the results from two consecutive phases of an international inter laboratory testing project referred to as the "CIMT monitoring panel". A total of 13 centers from six European countries participated in the study in which pre tested PBMC samples, synthetic peptides and PE-conjugated HLA-tetramers were prepared centrally and distributed to participants. All were asked to determine the number of antigen-specific T-cells in each sample using tetramer staining and one functional assay. The results of the first testing round revealed that the total number of cells analyzed was the most important determinant for the sensitive detection of antigen-specific CD8(+) T-cells by tetramer staining. Analysis by ELISPOT was influenced by a combination of cell number and a resting phase after thawing of peripheral blood mononuclear cells. Therefore, the experiments were repeated in a second phase but now the participants were asked to change their protocols according to the new guidelines distilled from the results of the first phase. The recommendations improved the number of antigen specific T-cell responses that were detected and decreased the variability between the laboratories. We conclude that a two-step approach in inter laboratory testing allows the identification of distinct variables that influence the sensitivity of different T-cell assays and to formally show that a defined correction to the protocols successfully increases the sensitivity and reduces the inter-center variability. Such "two-step" inter-laboratory projects could define rational bases for accepted international guidelines and thereby lead to the harmonization of the techniques used for immune monitoring. PMID- 17721784 TI - Nephron sparing surgery for renal cell carcinoma in a solitary kidney. AB - To determine functional and oncological outcomes of nephron sparing surgery (NSS) for renal cell carcinoma (RCC). We identified from our kidney database 103 consecutive patients undergoing NSS for solid renal tumors in a solitary kidney. After excluding 17 patients (16.5%) undergoing NSS with palliative intent in presence of preoperatively diagnosed metastatic disease (n = 15) or positive lymph nodes (n = 2) and 6 patients (5.8%) who turned out to have benign tumors, the remaining 80 patients with RCC were analyzed. Mean follow-up is 8.0 years (range: 0.1-25.8). Mean tumor size was 4.2 cm (range 1.2-11 cm). Chronic renal failure requiring hemodialysis developed after NSS in nine patients (11.2%). In the remainder, serum creatinine was 1.72 mg/dl (range: 0.45-4.6 mg/dl) at latest follow-up. The cancer specific survival rates at 1, 5 and 10 years were 97.2, 89.6 and 76%, respectively. The estimated local recurrence free survival rates at 1, 5 and 10 years were 97.8, 89.4 and 79.9%, respectively. Univariate analysis of correlation between clinical and pathologic features with death from RCC showed significant associations for grading and tumor size. The long-term data of our series support the concept of organ-sparing surgery for RCC in a solitary kidney since it provides excellent local tumor control and cancer specific survival and preserves renal function renal function so that 89% of patients remained free of dialysis in the long-run. PMID- 17721785 TI - [Laboratory diagnosis of rheumatic diseases. Part 3: arthritides caused by infection]. AB - This third part of this series of articles on laboratory diagnostics of rheumatic diseases considers the rheumatic diseases caused by infection by microorganisms, or reactive arthritides. The basis for laboratory diagnostics of infection reactive arthritides is the investigation of anti-infection antibodies. In some situations, DNA amplification methods may be helpful. Bacterially infected joints should be immediately examined by arthrocentesis and microscopic examination and laboratory culture of the synovial fluid. PMID- 17721786 TI - Skeletal muscle ergoreflex overactivity is not related to exercise ventilatory inefficiency in non-hypoxaemic patients with COPD. AB - Increased ventilatory response to the metabolic demand ("ventilatory inefficiency") is commonly found during dynamic exercise in patients with chronic obstructive pulmonary disease (COPD). However, the role of enhanced muscle ergoreflex activity on this phenomenon is yet unknown. Ten non-hypoxaemic patients with varying degrees of disease severity (median and range of post bronchodilator FEV(1) = 37.5 (27 to 70%) predicted) and 7 age- and gender-matched controls were studied. Subjects were submitted to wrist flexion tests to the limit of tolerance (Tlim) with and without post-exercise regional circulatory occlusion (PE-RCO) for 3 min. The muscle ergoreflex activity was quantified as the difference in ventilation between PE-RCO and control recovery periods corrected for the resting values (ergoreflex Delta). In addition, the area under the ventilatory curve in the recovery period was calculated in both conditions. We found that Tlim and the physiological stress associated with localized exercise did not differ between patients and controls. However, patients had increased ventilatory response to a given metabolic demand (VCO(2)), either at rest or during exercise (P < 0.05). There were no significant differences in ergoreflex Delta in patients and controls (-2.2 to 2.4 (0.2) vs. -0.6 to 1.8 (0.3) l/min, respectively). In addition, the area under the ventilatory curve in the recovery period did not differ between control and PE-RCO tests in patients and healthy subjects (P > 0.05). We conclude that increased muscle ergoreflex activity did not contribute to an excessive ventilatory response to exercise in patients with COPD-at least in non-hypoxaemic and non-cachetic subjects. PMID- 17721787 TI - Up-regulation of stress-inducible genes in tobacco and Arabidopsis cells in response to abiotic stresses and ABA treatment correlates with dynamic changes in histone H3 and H4 modifications. AB - Animal cells react to mitogenic or stress stimuli by rapid up-regulation of immediate-early (IE) genes and a parallel increase in characteristic modifications of core histones: chromatin changes, collectively termed the nucleosomal response. With regard to plants little is known about the accompanying changes at the chromatin level. We have used tobacco BY-2 and Arabidopsis T87 cell lines to study the nucleosomal response of plant cells to high salinity, cold and exogenous abscisic acid (ABA). When in quiescent stage, both tobacco and Arabidopsis cells show the typical nucleosomal response to high salinity and cold stress, manifested by rapid transient up-regulation of histone H3 Ser-10 phosphorylation, immediately followed by transient up-regulation of H3 phosphoacetylation and histone H4 acetylation. For each of the studied stresses the observed nucleosomal response was strictly correlated with the induction of stress-type specific genes. The dynamics of histone modifications in BY-2 cells in response to exogenous ABA exhibited a more complex pattern than that evoked by the two abiotic stresses, probably due to superposition of the primary and secondary effects of ABA. A rapid increase in H3 Ser-10 phosphorylation was also observed in whole leaves subjected to high salinity; however, the rate of change in this modification was much slower than in cultured cells. Together, these results indicate that the quiescent BY-2 and T87 cell lines show a typical nucleosomal response to abiotic stresses and ABA treatment and may represent suitable models for the study of chromatin-mediated mechanisms of stress tolerance in plants. PMID- 17721788 TI - Photosynthetic H2 metabolism in Chlamydomonas reinhardtii (unicellular green algae). AB - Unicellular green algae have the ability to operate in two distinctly different environments (aerobic and anaerobic), and to photosynthetically generate molecular hydrogen (H2). A recently developed metabolic protocol in the green alga Chlamydomonas reinhardtii permitted separation of photosynthetic O2 evolution and carbon accumulation from anaerobic consumption of cellular metabolites and concomitant photosynthetic H2-evolution. The H2 evolution process was induced upon sulfate nutrient deprivation of the cells, which reversibly inhibits photosystem-II and O2-evolution in their chloroplast. In the absence of O2, and in order to generate ATP, green algae resorted to anaerobic photosynthetic metabolism, evolved H2 in the light and consumed endogenous substrate. This study summarizes recent advances on green algal hydrogen metabolism and discusses avenues of research for the further development of this method. Included is the mechanism of a substantial tenfold starch accumulation in the cells, observed promptly upon S-deprivation, and the regulated starch and protein catabolism during the subsequent H2-evolution. Also discussed is the function of a chloroplast envelope-localized sulfate permease, and the photosynthesis-respiration relationship in green algae as potential tools by which to stabilize and enhance H2 metabolism. In addition to potential practical applications of H2, approaches discussed in this work are beginning to address the biochemistry of anaerobic H2 photoproduction, its genes, proteins, regulation, and communication with other metabolic pathways in microalgae. Photosynthetic H2 production by green algae may hold the promise of generating a renewable fuel from nature's most plentiful resources, sunlight and water. The process potentially concerns global warming and the question of energy supply and demand. PMID- 17721789 TI - Direct determination of the effects of genotype and extreme temperature on the transposition of roo in long-term mutation accumulation lines of Drosophila melanogaster. AB - Transposable elements (TEs) are mobile repetitive DNA sequences that constitute a structurally dynamic component of genomes. In order to understand the dynamics of TEs it is necessary to have information about the control of transposition and its dependence of environmental factors. After a great deal of previous work on transposition conducted on long-term mutation accumulation (MA) lines of Drosophila melanogaster started in 1987, only roo out of 16 families was found active in this genotype. Here we test the effect of the modification of the genetic background by introducing a Cy chromosome, and the effect of extreme temperature (28 degrees C) on the transposition rate of roo. Thermal stress did not affect the transposition rate, whereas the presence of a Cy chromosome in heterozygosis lowered it. There was an excess of insertions in the X chromosome, with respect to autosomes, and in the proximal and distal regions of chromosome arms that can be interpreted as target site preference. One of the control lines became highly unstable with mean insertion and excision rates of 3.0 x 10(-3) and 8.5 x 10(-4), respectively. Instability arose spontaneously during generations of mutation accumulation, and can be attributed to "de novo" mutation. Transposition in the unstable line could be directly studied on the progeny of individual males and females, from where we deduced that transposition occurs mainly, if not exclusively, in males, with a rate of 1.125 insertions per gamete. In situ hybridization with an LTR probe showed that most excisions (12 out of 14) were precise. Our data show the prominent role of genotype in transposition control and can explain rapid turnovers in the genome without increasing the number of copies. PMID- 17721790 TI - Self-anastomosing ability and vegetative incompatibility of Tuber borchii isolates. AB - In this work, different mycelial isolates of the ectomycorrhizal fungus Tuber borchii were analysed for their ability to form self-anastomoses, which were monitored by time-lapse live-cell imaging, providing a description of the anastomosis process. Self-fusions were evidenced in three out of five isolates, with frequencies ranging between 50 and 88% of hyphal contacts. Time-lapse video microscopy evidenced that during pre-contact events, hyphae were capable of growth re-orientation functional to hyphal contact: the time elapsed between hyphal growth re-direction and complete fusion ranged from 115 to 200 min. After anastomosis, protoplasmic flow occurred between fused hyphae and nuclei could be detected in fusion bridges. Vegetative incompatibility was also assessed by analysing macroscopic and microscopic hyphal interactions between paired T. borchii mycelia. Both plate-pairing tests and microscopic analyses showed vegetative compatibility only within the same isolate, whereas different degrees of incompatible responses were observed in inter-isolate pairings. The diversity of T. borchii strains revealed by cytomorphological approaches is consistent with their genetic diversity obtained by molecular methods. PMID- 17721791 TI - Pharmacologically defined components of the normal porcine multifocal ERG. AB - Multifocal electroretinograms (mfERG) from isoflurane anesthetized pigs were recorded and sequential application of TTX, NMDA, APB and PDA were used to identify contributions to the mfERG from inner retinal neurons, ON-pathway, OFF pathway and photoreceptors. The cellular origins of the first-order kernel (K1) and the first slice of the second-order kernel (K2.1) porcine mfERG are contributed from both inner and outer retina. For the K1 waveform, the n1 involved responses of cone photoreceptors and OFF-bipolar cells. The leading edge of p1 is dominated by ON-bipolar cell depolarization. The rear edge of p1, n2 and p2 are dominated by ON-bipolar activities and shaped by the activities of OFF bipolar cells and retinal cells with NMDAr and voltage-gated sodium channels other than ganglion cells. The p3 is mainly inner retinal activities. For the K2.1 waveform, the p1 and n1 are the summation of activities of ON-, OFF-bipolar cells and retinal cells rich in NMDAr and voltage-gated sodium channels other than ganglion cells. The p2 seems to be related to the ganglion cells. Better understanding of the cellular origins of the normal porcine mfERG will be useful for comparing and defining the functional changes that may occur in diseased retinas. PMID- 17721792 TI - Cancer-associated retinopathy (CAR) with electronegative ERG: a case report. AB - Cancer-associated retinopathy (CAR) should be suspected in patients who present with visual symptoms such as rapid unexplained visual loss and seeing shimmering lights, with an abnormal ERG. Electronegative ERG responses are not exclusive to melanoma-associated retinopathy (MAR) but may be seen in CAR as well. We describe a patient with CAR who presented with an electronegative ERG. A 67-year old woman, who presented with complaints of seeing shimmering lights, underwent an extensive ophthalmological and electrophysiological examination. Best-corrected visual acuity was 7/10 in the right and 9/10 in the left eye. Goldmann visual fields showed relative central scotomata and concentric narrowing. Slit-lamp and fundus examination were normal as was fluorescein angiography. Rod-specific ERG responses were severely reduced, with electronegative maximal combined rod-cone responses and delayed cone-responses with normal amplitudes. Melanoma-associated retinopathy was suspected. Extensive dermatological and internal evaluation eventually revealed an oat-cell carcinoma in the right lung. The patient died of pneumonia 2 years after presentation. PMID- 17721793 TI - [Diagnosis of bone marrow disorders: is MRT sufficient?]. PMID- 17721795 TI - Changes in quantitative ultrasound in infants born at less than 32 weeks' gestation over the first 2 years of life: influence of clinical and biochemical changes. AB - Studies in preterm infants show reduced speed of sound (SOS) as measured by quantitative ultrasound (QUS) during the immediate neonatal period. There is a scarcity of data on SOS changes following hospital discharge. The aim of this study was to assess SOS over the first 2 years in preterm infants. Infants were recruited from a neonatal follow-up clinic. Tibial QUS was performed using the Omnisense 7000P scanner. Thirty-nine infants born at <32 weeks' gestation had a single SOS measurement (median 3,203 m/second, range 2,609-3,495) which correlated with corrected gestational age (CGA) (r = 0.8, P < 0.005). The majority of measurements were within the manufacturer's reference range for term infants. SOS standard deviation score (SDS) in infants aged 0-6 months CGA demonstrated a negative correlation with duration of total parenteral nutrition (r = 0.7, P < 0.05) and a positive correlation with serum phosphate (r = 0.6, P < 0.05.) Two groups of infants had serial measurements: eight had measurements performed at term CGA and early infancy (early) and seven had measurements in later infancy (late). In the early group SOS SDS increased (P < 0.005), and the greatest increase in SOS over time occurred in infants with the lowest SOS at term (r = 0.9). In the late group there was no significant change over time. SOS SDS change did not show any correlation to weight SDS change. Catch-up in SOS occurs postterm in most infants by 6 months and is independent of postnatal growth. Infants with the lowest SOS at term have the fastest rate of catch-up. The opportunity for catch-up may be greatest in early infancy. PMID- 17721796 TI - Combined effects of different food rations and sublethal copper exposure on growth and energy metabolism in common carp. AB - Common carp (Cyprinus carpio) were fed two different rations, 0.5% body weight (low ration; LR) and 5% body weight (high ration; HR), throughout acclimation, sublethal (64 microg/L) Cu exposure for 28 days, and a subsequent 2-week recovery period. Growth, liver water content, and liver energy stores were assessed during this period. Growth rates were elevated in HR fish compared to LR fish, as was the hepatic lipid content. This was associated with a higher water content in the livers of LR fish. Liver glycogen levels were similar in both feeding treatments and remained relatively stable during Cu exposure. Cu exposure caused a significant reduction in growth in both HR and LR fish. Reduction in growth coincided with significant changes in liver and blood composition. Liver lipid levels dropped significantly during the first days of the exposure in both feeding treatments, and the difference between LR and HR lipid levels disappeared during Cu exposure. During the first week of Cu exposure, the difference in liver water content disappeared as well, with a significant reduction of the water levels in the LR fish. A rise of hepatic protein was observed after 2 and 4 weeks of Cu exposure in the LR carp and after 4 weeks of exposure in the HR fish. Cu exposure led to pronounced increases in plasma ammonia concentrations in HR carp. Growth and energy stores recuperated during the 2-week recovery period in both feeding treatments. The observed changes during Cu exposure are probably related to physiological disturbances like hypoxia and stress, as well as an inhibition of ammonia excretion. PMID- 17721797 TI - Characterization of nitrous oxide emission from a rice-duck farming system in South China. AB - Agricultural activities are important contributors to the emissions of greenhouse gases. This study ascertained the dynamic emission of nitrous oxide (N(2)O) from a paddy field under a rice-duck farming system in South China. Two different cultivation and fertilizer treatments, namely, organic fertilizer + ducks (OF+D) and chemical fertilizer + ducks (CF+D) treatments, were employed in this study. Experimental data showed that diurnal variations of N(2)O emission were highly correlated with the activities of ducklings. The rates of N(2)O emission were normally increased in the early morning and late afternoon due to the frequent movement of ducklings at these time periods. Our study further revealed that the rates of N(2)O emission from the paddy field varied with the types of fertilizers used as well as with the stages of the rice growth. In general, the rates of N(2)O emission were higher for the CF+D treatment than for the OF+D treatment, whereas more N(2)O was emitted from the paddy field at the tillering stage than at the heading stage. The global warming potential with the use of the organic fertilizer was about 22% lower than with the use of the chemical fertilizer. PMID- 17721798 TI - The influence of salinity and dissolved organic carbon on the toxicity of copper to the estuarine copepod, Eurytemora affinis. AB - The objectives of this study were to determine the influence of salinity (2.5, 5, 15, and 25 ppt) at dissolved organic carbon (DOC) concentrations of 1.3-3.3 mg/L and DOC concentrations of 2, 4, 6, and 8 mg/L at a fixed salinity of 10 ppt on the acute toxicity (96-h LC50s) of copper to the sensitive estuarine copepod, Eurytemora affinis. For both salinity and DOC experiments, various other chemical constituents such as DOC, Ca2+, Cl(-), Mg2+, Na+, K+, SO4 (2-) , hardness, alkalinity, salinity, pH, temperature, and dissolved oxygen were measured at selected copper concentrations at test initiation and test termination. Dissolved copper, copper speciation, and organic copper complexation were measured at various test conditions during the salinity and DOC experiments. Ninety-six-hour dissolved copper LC50 values for the four salinities ranged from 58 microg/L (25 ppt) to 104 microg/L (5 ppt) with intermediate values of 71 microg/L (2.5 ppt) and 68 microg/L (15 ppt). The 58, 68, and 71 microg/L LC50 values were not significantly different. Copper LC50 values at 5 ppt were higher than at both 15 and 25 ppt. The isosmotic salinity of E. affinis is approximately 5-10 ppt, which was a likely factor for why the LC50 value increased for copper at 5 ppt. The dissolved copper 96-h LC50s for E. affinis increased from 76 to 166 microg/L as DOC increased from 2 to 8 mg/L. This result is not surprising and is consistent with reported values for other saltwater species. PMID- 17721799 TI - Cross-facial nerve graft: a report of chronically paralyzed facial muscle neurotization by a nerve graft. AB - A 21-year-old housewife with long-standing hemifacial paralysis on the left side decided to undergo the classic two-stage cross-facial nerve graft with muscle transfer. The first stage of the operation was performed successfully with the use of a sural nerve graft. After the appearance of Tinel's sign 8 months later, gain of function in the muscles of the paralyzed side was observed and negated the need for the second-stage muscle transfer. PMID- 17721800 TI - Epidermoid inclusion cysts After APTOS thread insertion: case report with clinicopathologic correlates. AB - The APTOS threading procedure is a relatively new method in antifacial ptosis surgery. The reported cases present a small percentage of minor complications. A 57-year-old woman experienced scarring after APTOS threading. Scar biopsy showed an epidermoid inclusion cyst. Epidermoid inclusion cysts are a potential complication of APTOS threading. Proper surgical technique may reduce their likelihood. PMID- 17721801 TI - Lower lid deformity secondary to autogenous fat transfer: a cautionary tale. PMID- 17721802 TI - Predictors of outcome after abdominal aortic aneurysm rupture: Edinburgh Ruptured Aneurysm Score. AB - BACKGROUND: Many surgeons adopt a selective policy of intervention for a ruptured abdominal aortic aneurysm (AAA). This study aimed to develop an objective method of identifying patients suitable for attempted repair. METHODS: Consecutive patients selected for attempted repair of ruptured AAA over a 31-month period (January 2000 to July 2002) were entered into an observational study. Altogether, 53 preoperative physiological and biochemical variables were recorded and related to operative outcome. RESULTS: A total of 105 patients underwent attempted repair of a ruptured AAA. There were 39 (37%) deaths in hospital or within 30 days of operation. On univariate analysis, hemoglobin <9 g/dl (p = 0.038), blood pressure <90 mmHg (p = 0.036), and Glasgow Coma Scale <15 (p = 0.016) were found to be risk factors that predicted death. Of 70 patients with no or one risk factor, 20 (29%) died. Of 30 patients with two factors, 15 (50%) died, and of the five patients with all three factors, four (80%) died. There was a significant association between mortality and cumulative risk factors (p = 0.003). CONCLUSION: These three risk factors are easily assessed in the emergency setting and might form the basis of a scoring system to inform the outcome of ruptured AAA. PMID- 17721803 TI - The yield and safety of thoracentesis in hematopoietic stem cell transplantation recipients. AB - The aim of this study was to assess the diagnostic value and safety of thoracentesis in hematopoietic stem cell transplantation (HSCT) recipients. We identified all hospitalized HSCT recipients who underwent thoracentesis from 1998 to 2006. We collected patients' clinical characteristics, indications for thoracenstesis, the complications of the procedure, and the etiology of the pleural effusion. A total of 50 thoracentesis findings were analyzed. Twenty-six patients underwent allogeneic HSCT, while 24 patients underwent autologous HSCT. The main indications for performing thoracentesis were to rule out infection and document or diagnose malignancy. Pleural effusions were characterized as exudate in 33 patients (66%). A specific diagnosis based on the thoracentesis was made in 13 patients (26%). These were malignancy in nine patients, parapneumonic in three patients, and empyema in one patient. The only documented complication was pneumothorax in five patients. The presence of exudative effusion and underlying solid malignancy were associated with specific diagnosis by thoracentesis (p = 0.0001 and 0.013, respectively). In spite of the tendency of HSCT recipients to develop pulmonary infections, complex parapneumonic effusions are rarely diagnosed by thoracentesis. The rate of complications is comparable to other patient populations. PMID- 17721805 TI - Minimally invasive video-assisted lateral lymphadenectomy: a proposal. PMID- 17721804 TI - A novel inhibitor of inducible nitric oxide synthase, ONO-1714, does not ameliorate hypoxia-induced pulmonary hypertension in rats. AB - A recent study showed that long-term administration of the inducible nitric oxide synthase (iNOS) inhibitor L-NIL reduced the development of pulmonary hypertension. The purpose of the present study was to identify the effect of an another iNOS inhibitor, ONO-1714, on the development of pulmonary hypertensive vascular changes in chronic hypoxic pulmonary hypertension in rats. ONO-1714 was administered to rats exposed to hypobaric hypoxia (air at 380 mmHg) for 10 days. Muscularization of normally nonmuscular peripheral arteries and medial hypertrophy of normally muscular arteries were assessed by light microscopy. iNOS mRNA and protein levels of the lung were assessed in normal and hypoxic rats. Chronic hypoxia induced pulmonary hypertension, right ventricular hypertrophy, and hypertensive pulmonary vascular changes. Although an acute single injection of ONO-1714 induced a significant increase in mean pulmonary artery pressure in chronic hypoxic pulmonary hypertensive rats, the increase was slight and transient. There were no significant differences among rats with and without long term administration of ONO-1714 in pulmonary artery pressure, right ventricular hypertrophy, medial wall thickness of muscular arteries, and the percentage of muscularized arteries at the alveolar wall and duct levels. Although there was a significantly increased expression of iNOS as assessed with the reverse transcription polymerase chain reaction in rats that were exposed to 10 days of hypobaric hypoxia, we could not detect a significant level of iNOS protein by Western blotting. ONO-1714 does not have a therapeutic role in preventing the development of chronic hypoxic pulmonary hypertension. PMID- 17721806 TI - Laparoscopic transhiatal esophago-gastrectomy after corrosive injury. AB - Esophago-gastric necrosis is a surgical emergency associated with high morbidity and mortality. We report a laparoscopic transhiatal esophago-gastrectomy performed on a 43-year-old male, presenting two hours after hydrochloric acid ingestion. A gastroscopy showed several oral mucosal ulcers, a significant edema of the pharynx and larynx, a necrosis of the middle and lower esophagus and of the gastric fundus and antrum. A conservative strategy with intensive care observation was initially followed. After a change of clinical signs, chest abdominal computed tomography was realized and a pneumoperitoneum with free fluid in the left subphrenic space and bilateral pleural effusions was in evidence. A laparoscopic exploration was proposed to the patient, and confirmed the presence of free peritoneal fluid and necrosis with perforation of the upper part of the stomach. A laparoscopic total gastrectomy with subtotal esophagectomy was performed; the procedure finished with an esophagostomy on the left side of the neck and a laparoscopic feeding jejunostomy (video). Total operative time was 235 minutes. After six months a digestive reconstruction with esophagocoloplasty by laparotomy and cervicotomy was easily realized thanks to the advantages (few adhesions, bloodless, and simple colic mobilization) of the previous minimally invasive surgery. PMID- 17721807 TI - Laparoscopic ultrasound as the primary method for bile duct imaging during cholecystectomy. AB - BACKGROUND: Intraoperative fluorocholangiography (IOC) has been the standard method for bile duct imaging during cholecystectomy. Laparoscopic ultrasound (LUS) has been evaluated as a possible alternative, but has been used less frequently. The authors examined the evolving use of these two methods to assess the relative utility of LUS as the primary method for routine bile duct imaging during laparoscopic cholecystectomy (LC). METHODS: This study analyzed a prospective database containing 423 consecutive cholecystectomies performed by one attending surgeon in an academic medical center between 1995 and 2005. RESULTS: Intraoperative bile duct imaging was performed in 371 (94%) of 396 LCs performed for cholelithiasis. As recorded, IOC was performed in 239 cases, LUS in 236 cases, and both in 104 cases. Choledocholithiasis was present in 50 patients (13%). Common bile duct stones (CBDS) were identified by LUS in 3% of the patients without preoperative indicators of CBDS, and in 10% of the patients with one or more indicators. As shown by the findings, LUS had a positive predictive value of 100%, a negative predictive value of 99.6%, a sensitivity of 92.3%, and a specificity of 100% for detecting CBDS. Also, LUS identified clinically significant bile duct anatomy in 6% of the patients. In 1995, LUS was used for 20% of cases, whereas by 2005, it was used for 97% of cases. Conversely, the use of IOC decreased from 93% to 23%. CONCLUSIONS: With moderate experience, LUS can become the primary routine imaging method for evaluating the bile duct during LC. It is as reliable as IOC for detecting choledocholithiasis. In addition, LUS can locate the common bile duct during difficult dissections. On the basis of this experience, LUS is used currently in nearly all LCs and is the sole method for bile duct imaging in 75% of these cases. IOC is used as an adjunct to LUS when LUS imaging is inadequate, when stronger clinical indicators of choledocholithiasis are present, or when biliary anatomy remains uncertain. PMID- 17721808 TI - Laparoscopy versus laparotomy in management of abdominal trauma. AB - BACKGROUND: A majority of abdominal injuries (AIs) are associated with shock, hence most of the patients are hemodynamically unstable, which limits the use of video-assisted laparoscopy (VAL) in their management. The purpose of this study is to demonstrate the possibility of using VAL in management of stable and unstable patients with abdominal trauma. METHODS: In a period of six years 2,695 patients with AIs were evaluated. The subjects were evaluated retrospectively and divided into two groups. Group 1, consisting of 1,363 patients, had conventional routine investigations following which they underwent laparotomy for confirmatory diagnosis and definitive management. The second group, consisting of 1,332 patients, underwent diagnostic laparoscopy in addition to the conventional investigations in the first group; 411 patients of this group had therapeutic laparoscopy. Demographic information, incidence of organs injuries and operative findings, success rate of VAL and laparotomy repair, complications, associated injuries, and hospital mortality were evaluated. RESULTS: The age of 62.6% of our patients was 20-50 years, while 10.6% and 14.5% were less than 19 and greater than 50 years, respectively. Associated injuries were head, chest, musculoskeletal, and vertebral column. Most of the victims presented with shock; 50.7%, 24.7%, and 15.9% of the patients were in mild, moderate, and severe shock respectively, and 8.7% of the subjects had stable hemodynamic status. In the first group 47.1% of the laparotomies were absolutely indicated and 24.4% were negative. Of the patients who had laparotomy, 26.0% would have been managed confidently by VAL. In the second group following VAL 42.5% of the patients did not require surgical intervention. VAL surgery was performed in 30.8% of patients. Conversion to laparotomy was performed in 26.7% of the patients. CONCLUSIONS: The VAL technique can be confidently used as a main tool to expedite evaluation and treatment of patients with abdominal trauma in cases of both stable and unstable hemodynamic status. PMID- 17721809 TI - Ubiquitylation of epsilon-COP by PIRH2 and regulation of the secretion of PSA. AB - Ubiquitylation appears to be involved in the membrane trafficking system including endocytosis, exocytosis, and ER-to-Golgi transport. We found that PIRH2, which was identified as an interacting protein for androgen receptor or p53, interacts with and ubiquitylates the epsilon-subunit of coatmer complex, epsilon-COP. PIRH2 promotes the ubiquitylation of epsilon-COP in vitro and in vivo and consequently promotes the degradation of epsilon-COP. The interaction between PIRH2 and epsilon-COP is affected by the presence of androgen, and PIRH2 in the presence of androgen promotes ubiquitylation of epsilon-COP in vivo. Furthermore, overexpression of the wild type of PIRH2 in prostate cancer cells causes downregulation of the secretion of prostate-specific antigen (PSA), a secretory protein in prostate epithelial cells and one of diagnostic markers for prostate cancer. Our results indicate that PIRH2 functions as a regulator for COP I complex. PMID- 17721811 TI - Interactions of K+ATP channel blockers with Na+/K+-ATPase. AB - Two K(+) (ATP) channel blockers, 5-hydroxydecanoate (5-HD) and glyburide, are often used to study cross-talk between Na(+)/K(+)-ATPase and these channels. The aim of this work was to characterize the effects of these blockers on purified Na(+)/K(+)-ATPase as an aid to appropriate use of these drugs in studies on this cross-talk. In contrast to known dual effects (activating and inhibitory) of other fatty acids on Na(+)/K(+)-ATPase, 5-HD only inhibited the enzyme at concentrations exceeding those that block mitochondrial K(+) (ATP) channels. 5-HD did not affect the ouabain sensitivity of Na(+)/K(+)-ATPase. Glyburide had both activating and inhibitory effects on Na(+)/K(+)-ATPase at concentrations used to block plasma membrane K(+) (ATP) channels. The findings justify the use of 5-HD as specific mitochondrial channel blocker in studies on the relation of this channel to Na(+)/K(+)-ATPase, but question the use of glyburide as a specific blocker of plasma membrane K(+) (ATP) channels, when the relation of this channel to Na(+)/K(+)-ATPase is being studied. PMID- 17721810 TI - Chronic alcohol-induced oxidative endothelial injury relates to angiotensin II levels in the rat. AB - The link between chronic alcohol consumption and cardiovascular injury including hypertension is well known. However, molecular mediators implicated with alcohol induced elevation in blood pressure (BP) remain elusive. The aim of this study was to investigate the relationship of chronic ethanol-induced endothelial injury and elevation in BP with angiotensin II levels in rats. Male Fisher rats were divided into two groups of seven animals each and treated as follows: (1) Control (5% sucrose, orally) daily for 12 weeks and (2) ethanol (4 g kg(-1), orally) daily for 12 weeks. The BP (systolic, diastolic, and mean) was recorded every week. The animals were anesthetized with pentobarbital after 12 weeks; blood and thoracic aorta were isolated and analyzed for aortic reactivity response, angiotensin II levels, and oxidative endothelial injury. The results show that the systolic, diastolic, and mean BP were significantly elevated 12 weeks after ethanol ingestion. The increased BP was related to elevated angiotensin II levels in the plasma and aorta of alcohol treated group compared to control. The aortic NADPH oxidase activity, ratio of oxidized to reduced glutathione (GSSG/GSH) and lipid peroxidation significantly increased, whereas nitric oxide (NO), endothelial NO synthase (eNOS), and vascular endothelial growth factor (VEGF) protein expressions were depressed in alcohol group compared to control. The phenylephrine-mediated vasoconstriction response was not altered, while acetylcholine-mediated vasorelaxation response was depressed in the aorta of ethanol treated rats compared to control. It is concluded that chronic ethanol ingestion induces hypertension which is correlated with elevated tissue angiotensin II levels, activation of NADPH oxidase activity causing endothelial injury, depletion of endothelial NO generating system, and impaired vascular relaxation in rats. PMID- 17721812 TI - Face and emotion recognition in MCDD versus PDD-NOS. AB - Previous studies indicate that Multiple Complex Developmental Disorder (MCDD) children differ from PDD-NOS and autistic children on a symptom level and on psychophysiological functioning. Children with MCDD (n = 21) and PDD-NOS (n = 62) were compared on two facets of social-cognitive functioning: identification of neutral faces and facial expressions. Few significant group differences emerged. Children with PDD-NOS demonstrated a more attention-demanding strategy of face processing, and processed neutral faces more similarly to complex patterns whereas children with MCDD showed an advantage for face recognition compared to complex patterns. Results further suggested that any disadvantage in face recognition was related more to the autistic features of the PDD-NOS group rather than characteristics specific to MCDD. No significant group differences emerged for identifying facial expressions. PMID- 17721813 TI - Comparative sequence analysis of a highly oncogenic but horizontal spread defective clone of Marek's disease virus. AB - Marek's disease virus (MDV) is a cell-associated alphaherpesvirus that induces rapid-onset T-cell lymphomas in poultry. MDV isolates vary greatly in pathogenicity. While some of the strains such as CVI988 are non-pathogenic and are used as vaccines, others such as RB-1B are highly oncogenic. Molecular determinants associated with differences in pathogenicity are not completely understood. Comparison of the genome sequences of phenotypically different strains could help to identify molecular determinants of pathogenicity. We have previously reported the construction of bacterial artificial chromosome (BAC) clones of RB-1B from which fully infectious viruses could be reconstituted upon DNA transfection into chicken cells. MDV reconstituted from one of these clones (pRB-1B-5) showed similar in vitro and in vivo replication kinetics and oncogenicity as the parental virus. However, unlike the parental RB-1B virus, the BAC-derived virus showed inability to spread between birds. In order to identify the unique determinants for oncogenicity and the ''non-spreading phenotype'' of MDV derived from this clone, we determined the full-length sequence of pRB-1B-5. Comparative sequence analysis with the published sequences of strains such as Md5, Md11, and CVI988 identified frameshift mutations in RLORF1, protein kinase (UL13), and glycoproteins C (UL44) and D (US6). Comparison of the sequences of these genes with the parental virus indicated that the RLORF1, UL44, and US6 mutations were also present in the parental RB-1B stock of the virus. However with regard to UL13 mutation, the parental RB-1B stock appeared to be a mixture of wild type and mutant viruses, indicating that the BAC cloning has selected a mutant clone. Although further studies are needed to evaluate the role of these genes in the horizontal-spreading defective phenotype, our data clearly indicate that mutations in these genes do not affect the oncogenicity of MDV. PMID- 17721814 TI - Complete sequence of a subgroup 3.4 strain of classical swine fever virus from Taiwan. AB - Classical swine fever viruses from Taiwan have been classified into two subgroups (3.4 and 2.1). Outbreaks caused by 3.4 viruses were reported in Taiwan prior to 1996 and which mainly distributed in the geographic range from southern Japan to Taiwan. We have determined the complete sequence of a reference strain, 94.4/IL/94/TWN. The genome contains 12,296 nucleotides, encoding 3,898 amino acids flanked by a 372-nt region at the 5' untranslated region (UTR) and a 227-nt region at the 3'-UTR. Similarities of nucleotides among 3.4 viruses isolated from Taiwan and Japan (Kanagawa/74; Okinawa/86) maintained in 94.2-97.5%; however, comparing to subgroup 1.1 (ALD/64/Jap) and 2.1 (TD/96/TWN) only showed about 72.5 80.8%, respectively. Phylogenetic analysis based on positioning from 11,157 to 11,565 nt (NS5B region) revealed that CSFVs were divided into three major lineages and their sublineages. Strain 94.4/IL/94/TWN is the first completely genomic sequence of subgroup 3.4 viruses. PMID- 17721815 TI - Brain derived neurotrophic factor circulating levels in patients undergoing IVF. AB - PURPOSE: The aim of the study was to measure circulating BDNF levels, a neurotrophin recently identified in the ovary, in parallel with estradiol, to verify if assessing this factor could add any predictive value to the outcome of in vitro fertilization. METHODS: Blood sampling for BDNF and estradiol was performed in 23 subjects undergoing IVF on day 1 (D1), day 8 (D8), day of HCG administration (DHCG) and day of oocyte retrieval.(DOR). RESULTS: There was a positive correlation between BDNF and estradiol throughout the stimulation cycle in all subjects. In both pregnant and nonpregnant patients, the values of BDNF grew significantly only between D8 and DHCG and remained constant until DOR. Between-group comparisons showed no statistically significant differences in both BDNF and estradiol values throughout the IVF cycle. CONCLUSION: Although BDNF plasma concentrations are not seemingly predictive of IVF outcome, this neurotrophin is highly correlated to estradiol levels and seems to be an important factor especially in the periovulatory period. PMID- 17721816 TI - Intramuscular route of progesterone administration increases pregnancy rates during non-downregulated frozen embryo transfer cycles. AB - OBJECTIVE: The optimal route of progesterone (P4) administration in embryo transfer (FET) cycles remains to be determined. The objective of this study is to compare the pregnancy outcomes between intramuscular (IM) and vaginal progesterone (PV) administration for endometrial preparation in non-donor FET cycles. STUDY DESIGN: A retrospective clinical study in a private practice infertility setting. RESULTS: No significant differences in patient demographics and embryo characteristics were noted between the two groups. The clinical pregnancy rate as well as the live birth rate were significantly higher in the IM arm compared to the PV arm (38.2% vs 28%, 34.5 % vs 22.8%, respectively). CONCLUSION: Although both routes of progesterone administration had similar rates of initial positive pregnancy tests, the IM route had a significantly higher live birth rate. The exact reason for this difference remains to be determined. PMID- 17721817 TI - Extracellular interconversion of nucleotides reveals an ecto-adenylate kinase activity in the rat hippocampus. AB - Here, the extracellular interconversion of nucleotides and nucleosides was investigated in rat hippocampal slices and synaptosomes by an HPLC-UV technique. Adenosine 5'-triphosphate (ATP) was converted to adenosine 5'-diphosphate (ADP), adenosine 5'-monophosphate (AMP), adenosine, inosine, and hypoxanthine in the slices, whereas ADP elicited parallel and concentration-dependent formation of ATP and AMP. The specific adenylate kinase inhibitor diadenosine pentaphosphate decreased the rate of decomposition of ADP and inhibited the formation of ATP. No substantial changes in the interconversion of ADP to ATP and AMP were found in the presence of dipyridamole, flufenamic acid, the P2 receptor antagonist pyridoxal-5-phosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium (PPADS), and the alkaline phosphatase substrate para-nitrophenylphosphate. Negligible levels of nucleotides were generated when uridine 5'-diphosphate (UDP), AMP or adenosine were used as substrates. Ecto-adenylate kinase activity was also observed in purified synaptosomes. In summary, we demonstrate the presence of an ecto adenylate kinase activity in the hippocampus, which is a previously unrecognized pathway that influences the availability of purines in the central nervous system. PMID- 17721818 TI - Lipid peroxidation and antioxidant enzyme activities in vascular and Alzheimer dementias. AB - It has been reported that oxidative stress may play a role in the pathogenesis of dementia of the Alzheimer type (AD) and the cerebral ischemia which causes vascular dementia (VD). We measured malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) activities in blood samples from patients with AD and VD and in healthy non-demented controls (CTR) which similar ages to the patients, in order to evaluate the degree of oxidative stress in patients with AD and VD. A sample of 150 subjects consisting of 50 patients with AD; 50 patients with VD and 50 CTR, aged from 65 to 85 years on, was analyzed. Most of the changes observed were in SOD activity and MDA levels. Catalase activity were least affected. Significant differences were observed in SOD and GR activity between males and females in CRT and in patients with AD, but not in VD. We have found a decrease in antioxidant enzymes activities (SOD, CAT, GPx and GR) in patients with AD and VD and significant differences were observed between CRT and AD patients for ages from 65 to 74, 75 to 84 and from 85 years to 94 years in SOD activity and MDA levels (P < 0.001). MDA levels increase with age in VD, AD and CTR. No significant variation with respect to sex were detected, but significant variations in MDA levels were detected between CRT and patients with VD and AD (P < 0.001). We conclude that oxidative stress plays an important role in the brain damage for both AD and VD, being observed higher levels of oxidative stress for AD that for VD. PMID- 17721819 TI - Diabetic modulation of the temperature kinetics properties of cytochrome oxidase activity in rat brain mitochondria. AB - The effects of alloxan-diabetes and subsequent treatment with insulin on temperature kinetics properties of cytochrome oxidase activity from rat brain mitochondria were examined. The enzyme activity decreased only at the late stage of diabetes which was not normalized by insulin treatment; however at early stage of diabetes hyper-stimulation occurred. In the control animals the Arrhenius plot was chair shaped with three energies of (E1, E2 and E3) and two phase transition temperatures (Tt1 and Tt2). At early diabetic stage the Arrhenius plot became biphasic and E1)and E2 decreased; insulin treatment reversed chair-shaped pattern with increase in E2. These changes correlated with transient changes in the phospholipids profiles especially decreased acidic phospholipids. The temperature kinetics parameters were minimally affected at the late stage of diabetes or by insulin treatment. Thus at the late stage the brain tissue seems to have readjusted to its insulin homeostasis. PMID- 17721820 TI - Food reward-induced neurotransmitter changes in cognitive brain regions. AB - Recent evidence indicates that mechanisms involved in reward and mechanisms involved in learning interact, in that reward includes learning processes and learning includes reward processes. In spite of such interactions, reward and learning represent distinct functions. In the present study, as part of an examination of the differences in learning and reward mechanisms, it was assumed that food principally affects reward mechanisms. After a brief period of fasting, we assayed the release of three neurotransmitters and their associated metabolites in eight brain areas associated with learning and memory as a response to feeding. Using microdialysis for the assay, we found changes in the hippocampus, cortex, amygdala, and the thalamic nucleus, (considered cognitive areas), in addition to those in the nucleus accumbens and ventral tegmental area (considered reward areas). Extracellular dopamine levels increased in the nucleus accumbens, ventral tegmental area, amygdala, and thalamic nucleus, while they decreased in the hippocampus and prefrontal cortex. Dopamine metabolites increased in all areas tested (except the dorsal hippocampus); changes in norepinephrine varied with decreases in the accumbens, dorsal hippocampus, amygdala, and thalamic nucleus, and increases in the prefrontal cortex; serotonin levels decreased in all the areas tested; although its metabolite 5HIAA increased in two regions (the medial temporal cortex, and thalamic nucleus). Our assays indicate that in reward activities such as feeding, in addition to areas usually associated with reward such as the mesolimbic dopamine system, other areas associated with cognition also participate. Results also indicate that several transmitter systems play a part, with several neurotransmitters and several receptors involved in the response to food in a number of brain structures, and the changes in transmitter levels may be affected by metabolism and transport in addition to changes in release in a regionally heterogeneous manner. Food reward represents a complex pattern of changes in the brain that involve cognitive processes. Although food reward elements overlap with other reward systems sharing some neurotransmitter compounds, it significantly differs indicating a specific reward to process for food consumption. Like in other rewards, both learning and cognitive areas play a significant part in food reward. PMID- 17721822 TI - The effect of consumption of selenium enriched rye/wheat sourdough bread on the body's selenium status. AB - The potential of selenium-enriched rye/wheat sourdough bread as a route for supplementing dietary selenium intakes is reported. In addition to their normal diets, 24 female volunteers (24 to 25 years old) were fed either selenium enriched bread or non-enriched bread each day (68.02 and 0.84 microg selenium day(-1) respectively) for 4 weeks. The chemical form of the selenium in the bread had been characterised using HPLC-ICP-MS, which showed that 42% of the extractable selenium was present as selenomethionine. Plasma selenium levels and plasma platelet glutathione peroxidase (GPx1) activity were measured in the volunteers' blood over a 6-week period. A statistically significant difference (p = 0.001) was observed in the mean percentage change data, calculated from the plasma selenium level measurements for the enriched and control group, over the duration of the study. A comparable difference was not observed for the platelet GPx1 activity (p = 0.756), over the same period. Two weeks after cessation of the feeding stage, i.e., at t = 6 weeks, the mean percentage change value for the selenium plasma levels in the enriched group was still significantly elevated, suggesting that the absorbed selenium had been incorporated into the body's selenium reserves, and was then being slowly released back into the volunteers' blood. PMID- 17721823 TI - Impact of astaxanthin-enriched algal powder of Haematococcus pluvialis on memory improvement in BALB/c mice. AB - The impact of astaxanthin-enriched algal powder on auxiliary memory improvement was assessed in BALB/c mice pre-supplemented with different dosages of cracked green algal (Haematococcus pluvialis) powder daily for 30 days. The supplemented mice were first tested over 8 days to find a hidden platform by swimming in a Morris water maze. Then, for 5 days, the mice were used to search for a visible platform in a Morris water maze. After that, the mice practised finding a safe place--an insulated platform in a chamber--for 2 days. During these animal experimental periods, similar algal meals containing astaxanthin at 0, 0.26, 1.3 and 6.4 mg/kg body weight were continuously fed to each group of tested mice. Profiles of latency, distance, speed and the direction angle to the platforms as well as the diving frequency in each group were measured and analyzed. The process of mice jumping up onto the insulated platform and diving down to the copper-shuttered bottom with a 36 V electrical charge were also monitored by automatic video recording. The results of the Morris maze experiment showed that middle dosage of H. pluvialis meals (1.3 mg astaxanthin/kg body weight) significantly shortened the latency and distance required for mice to find a hidden platform. However, there was no obvious change in swim velocity in any of the supplemented groups. In contrast, the visible platform test showed a significant increase in latency and swim distance, and a significant decrease in swim speed for all groups of mice orally supplemented with H. pluvialis powder compared to the placebo group (P < 0.05 or P < 0.01). Mice supplemented with the algal meal hesitantly turned around the original hidden platform, in contract to mice supplemented with placebo, who easily forgot the original location and accepted the visible platform as a new safe place. These results illustrate that astaxanthin-enriched H. pluvialis powder has the auxiliary property of memory improvement. The results from the platform diving test showed that the low and middle dosage of H. pluvialis powder, rather that the high dosage, increased the latency and reduced the frequency of diving from the safe insulated platform to the electrically stimulated copper shutter, especially in the low treatment group (P < 0.05). These results indicate that H. pluvialis powder is associated with dose-dependent memory improvement and that a low dosage of algal powder (0.05). CONCLUSION: These results show that effective prevention of urinary stone formation should aim at restoring the urine's ability to inhibit calcium oxalate crystallization and more emphasis should be given to dietary measures. PMID- 17721829 TI - Inhibition of associative long-term depression by activation of beta-adrenergic receptors in rat hippocampal CA1 synapses. AB - The aim of this study was to investigate the role of beta-adrenergic receptors in modulating associative long-term depression (LTD) at CA1 synapses in rat hippocampal slices. Standard extracellular electrophysiological techniques were employed to record field excitatory post-synaptic potential (fEPSP) activity and to induce associative LTD. Two independent Schaffer collateral pathways were elicited in hippocampal CA1 areas. In one (weak) pathway, the stimulating intensity was adjusted to elicit small fEPSP activity (20-30% of the maximum response). In contrast, 80-90% of the maximum response was evoked in the other (strong) pathway. Associative LTD of weak pathway could be induced by paired stimulation of weak and the strong pathways, repeated 100 times at 0.167 Hz. The associative LTD of weak pathway was NMDA receptor- and phosphatase 2B dependent, because bath application of 50 microM D, L-AP5 or 10 microM cypermethrin blocked its induction. Bath application of 1 microM isoproterenol inhibited associative LTD, and this effect was blocked by timolol, suggesting the involvement of beta adrenergic receptors. The inhibitory effect of beta-adrenergic receptors on LTD induction was blocked in slices pretreated with inhibitors of protein kinase A and mitogen-activated protein kinase, suggesting that these signal cascades are downstream effectors following activation of beta-adrenergic receptors. Nevertheless, bath application of timolol or cypermethrin alone did not have significant effect on associative LTD induction, suggesting neither endogenous function of beta-adrenergic receptor nor endogenous PKA activity does have a role in associative LTD induction. PMID- 17721828 TI - Molecular characterization and evaluation of plant litter-associated fungi from the spring 'grazing corridor' of a sheep herd vulnerable to alveld disease. AB - This study sample and identify species of fungi on withered vegetation in the spring 'grazing corridor' from infields to Narthecium bogs for a sheep herd almost chronically vulnerable to phototoxic disease. Hepatogen photosensitizing disorders like alveld attack grazing sheep, especially lambs, in various parts of the world. It has been hypothesized that saponin metabolites in the monocotyledonous plant Narthecium ossifragum causes the disorder in Norway, however, this has not been verified. Thus, the search for other causal agents or saponin cofactors (the cofactor hypothesis) has been intensified, and endophytic poisonous fungi associated with dead N. ossifragum leaves and grasses are among the prime suspects. The fungal diversity was targeted by obtaining axenic cultures from surface-sterilized plant material, with subsequent DNA isolation, PCR, and sequencing of the ITS nrDNA region. The taxonomic affinities of the obtained sequences were thereafter explored by similarity searches against the public access sequence database EMBL/GenBank/DDBJ. Among the spectrum of identified taxa were representatives of Cladosporium, Fusarium, Penicillium, and Trichoderma, all of which are well known as potential producers of toxins. A possible involvement of these toxic species in the etiology of alveld is evaluated and discussed. PMID- 17721830 TI - Thyroid hormone-induced alterations in membrane structure-function relationships: studies on kinetic properties of rat kidney microsomal Na(+),K (+)-ATPase and lipid/phospholipid profiles. AB - The effects of thyroidectomy (Tx) and subsequent treatment with 3,5,3' triiodothyronine (T(3)) or combined replacement therapy (T(R)) with T(3 )and thyroxine (T(4)) on the substrate and temperature kinetics properties of Na+,K+ ATPase and lipid/phospholipid makeup of rat kidney microsomes were examined. Enzyme activity was somewhat high in the hypothyroid (Tx) animals and increased significantly following T(3) treatment, while T(R) treatment caused a decrease. In the Tx and T(3) groups enzyme activity resolved in two kinetic components, while in the T(R) group the enzyme showed allosteric behavior up to 0.5 mM: ATP concentration. The K(m) and V(max) values of both the components decreased in Tx animals without affecting the catalytic efficiency. T(3) treatment caused a significant increase in the V(max) of both the components, with a significant increase in the catalytic efficiency, while the K(m) values were not upregulated. The T(R) regimen lowered the K(m) and V(max) of component II but improved the catalytic efficiency. Thyroid status-dependent changes were also noted in the temperature kinetics of the enzyme. Regression analysis revealed that changes in the substrate and temperature kinetics parameters correlated with specific phospholipid components. PMID- 17721832 TI - [Pillars of quality in medical rehabilitation]. PMID- 17721831 TI - Low level of IGF-1 in obesity may be related to obstructive sleep apnea syndrome. AB - The aim of this study was to compare serum insulin-like growth factor (IGF-1) levels in patients with obstructive sleep apnea syndrome (OSAS) with those of nonapneic controls and to determine the risk factors of low IGF-1 levels in patients with OSAS. The study included 39 newly diagnosed moderate-to-severe OSAS patients and 36 nonapneic controls. Overnight polysomnography (PSG) was performed in all patients. The circulating levels of IGF-1 in the OSAS group were significantly lower than those of the control group (p < 0.05). There was a significant negative correlation between IGF-1 and logarithmic transformation (Ln) of the apnea-hypopnea index (AHI), duration of apnea-hypopnea, arousal index, average desaturation, and oxygen desaturation index (ODI). The result of stepwise regression analyses showed that OSAS (p = 0.001) was a risk factor for a low IGF-1 level, independent of age, gender, and body mass index (BMI). Our findings demonstrated that there was a significant negative correlation between IGF-1 and Ln AHI and that OSAS reduced the circulating levels of IGF-1. PMID- 17721833 TI - [Quality assurance in outpatient medical rehabilitation - concept and results of a pilot project to develop a quality assurance programme for musculoskeletal and cardiac diseases]. AB - PURPOSE: The concept and results of a pilot project to develop a quality assurance programme for outpatient medical rehabilitation in musculoskeletal and cardiac diseases are discussed. The processes developed and the results that were achieved using the instruments in 24 pilot institutions are described. METHODS: The quality of structure was assessed by defining and applying basic and detailed criteria; a version of peer review for outpatient treatment was developed to test the quality of process. The quality of results was determined by means of a prospective study with two or three measurement times and implementation of generic and disease-specific measurement instruments. The process was tested on n=1475 patients with musculoskeletal diseases and n=843 patients with cardiac diseases. RESULTS: The level of the quality of structure in the participating centres is quite high; 89-93% of the structure features required were fulfilled. The peer review indicated that the process had 25-40% serious shortcomings in cardiology and 15-20% for musculoskeletal diseases. The quality of results measurements show that the participating outpatient rehab centres achieved medium effects for the majority of the core rehab dimensions for the respective indications, but the findings also showed that at the time the follow-up reports were made there was often a reduction of positive effects and high effects were quite rare. While there were marked differences in quality of structure and process among the various institutions, there were only slight differences among the outpatient centres regarding quality of results. CONCLUSIONS: A scientifically sound quality assurance programme was developed that covers specific aspects of outpatient rehabilitation, to a great extent using the same structures that have been implemented in the quality assurance programmes for inpatient treatment. To implement the results presented here, the scientific findings will need to be evaluated in the respective committees of the cost carriers. The tests of the programme in 24 pilot institutions showed an overall high level of quality, but also revealed potential for improvement in some areas. PMID- 17721834 TI - [Guideline development for rehabilitation of breast cancer patients - phase 2: findings from the classification of therapeutic procedures, KTL-data-analysis]. AB - BACKGROUND: Aim of this project is the development of an evidence based guideline for the rehabilitation of breast cancer patients, funded by the German Pension Insurance scheme. The project consists of four phases. This paper is focused on the 2nd phase, i.e., analysis of procedures in rehabilitation based on evidence based therapeutic modules. METHODS: As a result of a systematic literature review 14 therapeutic modules were defined. From a total of 840 possible KTL Codes (Klassifikation Therapeutischer Leistungen, Classification of therapeutic procedures), 229 could be assigned to these modules. These analyses are based on 24685 patients in 57 rehabilitation clinics, who had been treated in 2003. For these modules the number of patients having received those interventions as well as the duration of the modules were calculated. The data were analysed with respect to the influence of age and comorbidity. Moreover, differences between rehabilitation clinics were investigated according to the category of interventions. RESULTS: Our findings show great variability in the use of the therapeutic modules. Therapeutic modules like Physiotherapy (91.6%), Training Therapy (85.2%) and Information (97.8%) are provided to most of the patients. Younger patients receive more treatments than older patients, and patients with higher comorbidity receive more Physiotherapie, Lymphoedema Therapy and Psychological Interventions than patients without comorbidities. DISCUSSION: Data analysis shows wide interindividual variability with regard to the therapeutic modules. This variability is related to age and comorbidity of the patients. Furthermore, great differences were found between the rehabilitation clinics concerning the use of the various interventions. This variability supports the necessity of developing and implementing an evidence based guideline for the rehabilitation of breast cancer patients. The next step will be discussing these findings with experts from science and clinical practice. PMID- 17721835 TI - [Predictors of the effectiveness of psychological sleep management in cancer patients during inpatient rehabilitation]. AB - Insomnia is a common phenomenon in cancer patients; nevertheless, there are only a few intervention results published covering this topic. In a former study we examined the effects of a psychological sleep management programme with two intervention groups (n=80, n=71) and one control group (n=78) and showed significant improvements over time, indicating that 50% to 80% of the intervention group participants benefited with moderate or large scale effects on several sleep variables. Now we reanalysed data to look for predictors for those patients who improved best. Almost no demographic, cancer-related or quality of life variables predicted treatment response and persons with greater sleep disturbances at the beginning do benefit the same as persons with less problems. Additionally, better acceptance of the chosen intervention form (cognitive behavioural programme with autogenic training or with muscle relaxation technique) positively predicted good outcome. Explained variance associated with different outcome variables varied between 9% and 18%. Therefore training should be offered for all cancer patients with sleep problems, and they should have a choice between different relaxation techniques. PMID- 17721836 TI - [Immediate effects of therapeutic interventions on the central motor system and their practical consequences]. AB - Physiotherapy and occupational therapy have changed over recent years influenced by our growing neurophysiological knowledge especially about motor learning. Understanding the direct effects of therapeutic interventions on the central motor system is crucial for further development of therapeutic approaches. Recent studies are discussed dealing with the facilitatory effects of different therapeutic interventions and the question whether or not the activation of the healthy upper limb has a facilitatory or inhibitory net-effect on the damaged central motor system. In a controlled study using transcranial magnetic stimulation (TMS) we could show that motor system excitability is not influenced by the contraction type (isometric or isotonic), neither in healthy nor in stroke patients. Two TMS-studies could show that voluntary exercises of the non-affected hand alone or in bimanual tasks do not have an inhibitory effect on the damaged central motor system. However, the strongest facilitation of the damaged motor area could be achieved by voluntary activation of the affected extremity. The therapeutic approach in severely or completely paretic upper limbs should, hence, be focussed on functional compensation. As soon as voluntary activity is obtainable intensive voluntary exercises should however be preferred, with contraction type (isometric or isotonic) seeming not to be important. PMID- 17721837 TI - [Company centredness in the rehabilitation system of the German Democratic Republic, GDR]. AB - This article describes major aspects of the rehabilitation system of the former German Democratic Republic, GDR. Based on presentation of the actors in the medical and occupational rehabilitation system, differences are pointed out in comparison to the notion of rehabilitation in the former Federal Republic of Germany, FRG. The article focuses on the system of rehabilitation after stroke, which is outlined with relevant scientific literature. The health and rehabilitation system of the GDR was company-centred. Patients in rehabilitation received comprehensive care and guidance, and especially the companies played an integrative part and adjusted the occupational activity of the patients in rehabilitation to their physical and mental abilities in order to avoid early retirement. On account of the political and social transformation process as well as transfer of the health and rehabilitation legislation of the old FRG, the company-centred rehabilitation system of the GDR was replaced, implementing West German rehabilitation structures in East Germany as well. PMID- 17721838 TI - [Properties and benefits of applying the Rasch model in clinical diagnostics]. AB - In medical rehabilitation settings the use of appropriate assessment instruments is essential in many ways. A high quality of psychometric scales has to be ensured in order to allow for an appropriate interpretation of diagnostical data as well as for the evaluation of treatment outcomes and for quality assurance within rehabilitation clinics. Assessment scales developed by means of Rasch analysis possess desirable properties, especially because person parameters reach interval level by definition, and the assumption of only one latent dimension suffices to predict respondents behaviour sufficiently. Accordingly, Rasch scales are strictly one-dimensional and thus allow for unambiguous interpretation of diagnostic results. In this article it is shown which specific properties characterize Rasch scales and how Rasch analysis can be used in order to allow for a more differentiated and clinically meaningful data interpretation and to enhance analysis of clinical data. PMID- 17721839 TI - [Patient-individual care pathways in phase D neurological rehabilitation]. AB - The "patient-individual neurological care pathways" are a concept for qualified decision-making about rational rehabilitative strategies in the treatment of neurological diseases. Such clinical pathways include available scientific evidence and treatment guidelines. In neurological rehabilitation all treatments have a decidedly interdisciplinary character. All members of the team need highly specialized knowledge, a high potential for teamwork, as well as efficient organisation of work time. Here, computer aided decision-making tools such as the "patient-individual neurological care pathways" facilitate rational decisions and reduce the need for reorganization of therapies. In rehabilitation of neurological patients a symptom-oriented and function-related perspective of the individual treatment goals is indispensable for optimal choice of therapy approaches. This function-oriented classification of patients and creation of individual treatment plans are realized within the Excel-based care pathways. This system has been proved on the one hand as an instrument for streamlining and optimisation and, on the other, as a useful tutoring tool in the medical rehabilitation process. PMID- 17721840 TI - [First German Rehab Law Day May 11, 2007 in Berlin - a report]. PMID- 17721841 TI - Cardiac surgery in Germany during 2006: a report on behalf of the German Society for Thoracic and Cardiovascular Surgery. AB - All cardiac surgical procedures performed in 81 German cardiac surgical units throughout the year 2006 are presented in this report, based on a voluntary registry which is organized by the German Society for Thoracic and Cardiovascular Surgery. In 2006 a total of 97,123 cardiac surgical procedures (ICD and pacemakers procedures excluded) have been collected in this registry. More than 9.6 % of the patients were older than 80 years compared to 8.4 % in 2005. Hospital mortality in 51,273 isolated CABG procedures (10.1 % off-pump) was 3.1 %. In 20,028 isolated valve procedures a mortality of 4.9 % has been observed. This registry will continue to be an important tool of the German Society for Thoracic and Cardiovascular Surgery enabling a continuous and voluntary quality assurance and illustrating the development of cardiac surgery in Germany. PMID- 17721842 TI - Impact of graft size and resuspension level of the commissures on aortic insufficiency after reimplantation of the aortic valve. AB - BACKGROUND: In addition to the size of the graft, the resuspension of the commissures has been described as important for valve function in valve-sparing aortic root replacement procedures. This study describes the influence of a stepwise reduction of the fixation level of the commissures within the graft as well as a stepwise reduction of graft size on valve insufficiency. METHOD: Porcine aortic valves were reimplanted into a tubular graft and the height of the commissures was reduced in a stepwise manner. In a second series of experiments, the diameter of the grafts was reduced by 30 % and 50 %. RESULTS: A reduction of the commissure heights by 10 % and 20 % caused a significant increase in reflux water. Using the criteria of homograft preparation, a 10 %, but not a 20 %, reduction was tolerated. The coaptation level of the valve became increasingly lower, indicating a higher risk for late valve incompetence. A reduction of the prosthesis diameter by 30 % and 50 % did not result in insufficiency of the valve but it lowered the coaptation level. CONCLUSION: Resuspension of the commissures within the graft has a more important impact on early failure rates than the choice of graft size. PMID- 17721843 TI - Intraoperative bypass graft angiography: cooperation between cardiologist and surgeons in the operation room for optimal postoperative results -- is this the way for the future? AB - OBJECTIVE: To confirm the quality of total arterial CABG carried out using the left internal thoracic artery (LITA) and a radial artery (RA) T-graft and distal anastomoses immediately in the OR, we developed a new technique using intraoperative graft angiography. METHODS: A 5-Fr sheath is inserted in the proximal radial artery stump, through which a catheter for LITA angiography is later introduced. From July 2004 to March 2005, 23 patients underwent total arterial CABG with the T-graft and intraoperative graft angiography. RESULTS: On pump CABG was performed in 22 patients and off-pump CABG in 1 patient. Mean procedure time for the angiography was 13.7 +/- 7.3 minutes, and mean fluoroscopy time was 6.2 +/- 4.6 minutes. In two patients, the RA-marginal artery side-to side anastomosis was stenosed and had to be revised as demonstrated by graft angiography. In one patient, the RA was kinked and in another, there was a kinking of the LITA. In both cases, kinking was corrected. The remaining anastomoses were seen to have unobstructed flow with no evidence of stenosis. CONCLUSIONS: Intraoperative graft angiography can be performed in patients undergoing total arterial CABG. This concept of intraoperative cooperation between an interventional cardiologist and surgeons could significantly improve the operative outcome in CABG surgery. PMID- 17721844 TI - How well are patients doing up to 30 years after a mustard operation? AB - BACKGROUND: Right heart failure and baffle complications may affect the health status of patients with transposition of the great arteries after an atrial switch operation. METHODS: This study aims to identify risk factors for late death, the incidence of reoperations, and the functional status of 88 patients who underwent a Mustard operation with a mean follow-up of 20.9 +/- 10.0 years. RESULTS: There were 7 early and 19 late deaths. Follow-up was complete for 97 % of the hospital survivors. Survival and freedom from reoperation of the hospital survivors at 20 years was 83.7 +/- 4.2 %, and 70.6 +/- 5.4 %, respectively. Seven reoperations were performed for systemic ventricular failure, and 24 for baffle complications, with no operative mortality. Presence of a ventricular septal defect at the time of the Mustard operation was predictive for late death in multivariate analysis ( P = 0.040). At follow-up, 82 % of the patients were able to work full-time, 11 % part-time, and 7 % experienced noticeable limitations of their activities. CONCLUSIONS: Presence of a VSD at the time of the Mustard operation defines a distinct subgroup with an increased risk for late death. Long term survivors were in a good functional status but had to be reoperated frequently due to baffle complications that seemed to increase in adulthood. PMID- 17721845 TI - Echocardiographic evaluation of the left atrium and left atrial appendage function in patients with atrial septum aneurysm: implications for thromboembolic complications. AB - BACKGROUND: Our study aimed to assess left atrium (LA) and left atrial appendage (LAA) function in patients with atrial septum aneurysm (ASA) and to relate it to thromboembolic complications. METHODS: The study group comprised 25 patients with isolated ASA (group I) and 17 clinically healthy subjects (control group = group II). Transthoracic and transesophageal echocardiography were performed in all investigated patients. RESULTS: In group I, the following parameters were significantly higher than in the controls: LA minimal dimension (LA (min)) was 2.13 vs. 1.7 cm; LA presystolic dimension (LA (a)) was 2.66 vs. 2.29 cm and LA pre-ejection period/LA ejection time index (PEP/ETLA) was 1.26 vs. 0.41 ( P < 0.05). There were no statistically significant differences between groups as to P wave and PR-interval duration, which were 69 vs. 72 ms and 167 vs. 173 ms, respectively. All LAA parameters were investigated, but LAA minimal areas (LAA (area min)) were higher in the study group than in controls: LAA transversal dimension (LAA (trans)) was 1.89 vs. 1.32 cm; LAA longitudinal dimension (LAA (long)) was 4.24 vs. 3.11 cm; LAA maximal area (LAA (area max)) was 4.35 vs. 3.1 cm (2); LAA ejection fraction (EFLAA) was 56 vs. 33 %; LAA peak emptying (LAAE) was 0.64 vs. 0.41 m/s, and filling velocities (LAAF) was 0.55 vs. 0.42 m/s ( P < 0.05). The results indicate a depression of LA systolic and an enhancement of LAA function in patients with ASA compared with clinically healthy subjects. CONCLUSION: (1) Atrial septum aneurysm impairs left atrium systolic function. (2) In patients with atrial septum aneurysm, left atrium appendage function changes; its systolic as well as a reservoir function improve. (3) The enhancement of LAA function in ASA may be a compensatory mechanism for LA systolic function deterioration. (4) As LAA systolic function is enhanced, it is rather unlikely that LAA is the place of origin of thrombi, which occur relatively frequently (according to the literature) in patients with ASA. The thrombi seem to be formed in the bulging sack of ASA, i.e., in the part of the LA whose systolic function is depressed. PMID- 17721847 TI - Surgical treatment of long-segment tracheal anomalies in infants and children. AB - BACKGROUND: Tracheal stenosis in combination with vascular and/or cardiac anomalies is a life-threatening condition in infants and children presenting with severe symptoms of airway obstruction. The optimal surgical treatment of these cases remains controversial. OBJECTIVES: We present here a group of infants and children with combined tracheal malformations and vascular and/or cardiac anomalies. More than 30 % of the stenotic trachea was resected in a subgroup of the patients. A reconstruction with end-to-end anastomosis was achieved on the basis of extensive mobilization of the whole tracheobronchial tree and use of CPB. METHODS: The clinical outcome in 37 children with a median age of 8 (1 - 72) months was analyzed retrospectively. The patients presented with severe airway obstruction in combination with congenital heart defects and/or vascular anomalies. Cardiac catheterization, bronchoscopy and thoracic computer tomography were performed prior to operation. The operations were performed under CPB and consisted of tracheal resection with end-to-end anastomosis or external stabilization. Associated intracardiac and vascular anomalies were repaired simultaneously. RESULTS: All but 1 patient survived and had a straightforward recovery. The patients were extubated under bronchoscopic control with a median intubation time after airway repair of 12.2 days. The average follow-up was 8.4 years (1 - 14 years) and the surviving patients did not show signs of restenosis clinically. A segment longer than 30 % of the tracheal length was resected and reconstructed with end-to-end anastomosis in 57 % of the patients (12 of 21 patients). CONCLUSIONS: Our experience demonstrates that resection of tracheal stenosis and end-to-end anastomosis can be achieved successfully even in cases with stenosis of more than 30 % of the total tracheal length. The use of CBP allowed extensive mobilization of the tracheobronchial tree and resection with end-to-end tension-free anastomotic reconstruction. PMID- 17721846 TI - Omental flap for recurrent deep sternal wound infection and mediastinitis after cardiac surgery. AB - BACKGROUND: Unsuccessful surgical treatment of deep sternal wound infection (DSWI) and mediastinitis may lead to sepsis, multiorgan failure and death. Omental flap transposition (OFT) may, in this situation, be the only effective therapy. METHODS: Twenty-seven patients with DSWI and mediastinitis after one or more unsuccessful surgical attempts to cure the infection were treated by OFT. Forty-one interventions (1.5/patient) consisting of closed irrigation technique, bilateral pectoralis flap reconstruction and vacuum-assisted therapy were performed before carrying out OFT. RESULTS: Operative mortality was 0. Mean postoperative ventilation time was 1.38 days and mean time in the intensive care unit was 4.7 days. Hospital mortality was 7.4 % (n = 2). Mean follow-up time was 2 years. One patient (4 %) died one year after discharge. During follow-up, abdominal wall hernia occurred in one patient (4 %) and presternal fistula resection was necessary in another patient (4 %). CONCLUSION: OFT is, in our experience, the most effective procedure for the treatment of recurrent DSWI and mediastinitis after cardiac surgery. Early mortality is acceptable, morbidity is low and late results are very good. PMID- 17721848 TI - Independent predictors for early and midterm mortality after thoracic surgery. AB - BACKGROUND: The purpose of the present study was to determine independent predictors for early and midterm mortality for the whole context of thoracic surgery. METHODS: We studied 1453 consecutive patients who underwent thoracic surgery between 2002 and 2005. Operations included lung resections (n = 504), mediastinal (n = 468), pleural and pericardial (n = 226), esophageal (n = 83), chest wall (n = 85), tracheal (n = 50) and other procedures (n = 37). Midterm survival data (mean follow-up 2.0 +/- 1.1 years) were obtained from the National Death Index. Multivariate logistic regression was used to assess in-hospital mortality. Independent predictors for midterm mortality were determined by multivariate Cox regression analysis. RESULTS: There were 47 (3.2 %) in-hospital and 312 (21.5 %) late deaths. Independent predictors for in-hospital mortality included Zubrod score (OR 2.72, P < 0.001), ASA score (OR 3.42, P < 0.001), pneumonectomy (OR 20.71, P = 0.001) and no history of cerebrovascular events (OR 0.27, P = 0.011). Independent predictors for midterm mortality included age (HR 1.03, P < 0.001), weight loss (HR 1.57, P = 0.005), Zubrod score (HR 1.47, P < 0.001), primary lung cancer (HR 1.98 P < 0.001), intrathoracic extrapulmonary metastases (HR 2.78, P < 0.001), primary chest wall tumor (HR 0.14, P = 0.008), diabetes requiring insulin (HR 1.71, P = 0.017), no preoperative renal failure (HR 0.57, P = 0.004), no comorbidities (HR 0.54, P = 0.009), ASA score (HR 1.69, P < 0.001), postoperative radiation treatment (HR 1.90, P = 0.016), pneumonectomy (HR 2.18, P = 0.040), reoperation for bleeding and/or postoperative transfusion (HR 3.10, P = 0.027) and postoperative pulmonary complications (HR 1.89, P = 0.013). CONCLUSIONS: We determined independent predictors for in-hospital and midterm mortality for the whole context of thoracic surgery. Zubrod and ASA scores affect both early and midterm mortality. PMID- 17721849 TI - Haemostatic fleece (TachoComb) to prevent intrapleural adhesions after thoracotomy: a rat model. AB - BACKGROUND: Postoperative adhesion is a complication common to all surgical subspecialties. TachoComb is a collagen fleece with properties well suited to the prevention of adhesion. This preclinical study was performed to evaluate the efficacy and mechanism of action of TachoComb in the prevention of adhesion following pleural injury during thoracic surgery. METHODS: Rats (n = 72) were randomised to receive saline or TachoComb following pleural injury. The macroscopic severity of adhesion formation and histological changes were assessed following euthanasia at time points up to 28 weeks post-operation. Levels of the biochemical markers t-PA, PAI-1 and bFGF were measured in intrapleural lavage fluid. RESULTS: The severity of adhesion was lower in TachoComb-treated animals compared with control animals at all time points (mean adhesion score: 1.4 vs. 4 at week 28 post-operation; P < 0.01). Regeneration of the mesothelial cell stratum occurred faster in TachoComb-treated animals, and a significantly lower PAI-1 activity was observed (14.32 vs. 23.28 U/ml; P < 0.01). CONCLUSIONS: TachoComb is effective in the prevention of adhesion following thoracic surgery, both by acting as a physical barrier and by inhibiting PAI-1 activity. PMID- 17721850 TI - Role of diffusing capacity in predicting complications after lung resection for cancer. AB - BACKGROUND: The purpose of our study was to determine whether the assessment of the diffusing capacity of the lung for carbon monoxide (DL (CO)), together with the forced expiratory volume in 1 second (FEV (1)), could improve the selection of surgical patients. METHODS: The data of 76 patients undergoing major lung resection (pnemonectomy, bilobectomy or lobectomy) for non-small cell lung cancer were retrospectively studied. All patients were reviewed for age, sex, preexisting medical conditions, operative, and pathological findings and postoperative outcome. RESULTS: Univariate and multivariable logistic regression analysis showed that ppoFEV (1) and ppoDL (CO) were the only statistically significant predictors of pulmonary complications. In the group of patients with marginal ppoFEV (1) (between 30 - 40 %), ppoDL (CO) predicted pulmonary morbidity with a better accuracy ( P < 0.005) than ppoFEV (1) ( P > 0.05). Multiple regression analysis showed that pneumonectomy was the only statistical factor correlated with mortality ( P < 0.05). CONCLUSION: Our experience seems to suggest that ppoDL (CO) is a strong predictor of pulmonary complications after major lung resection, allowing a better surgical selection of the patients with compromised respiratory function. PMID- 17721851 TI - Rare association of a patient with Alagille syndrome and mitral valve regurgitation. AB - A 9-year-old patient with known Alagille syndrome presented to our institution with progressive mitral valve regurgitation due to prolapse of the posterior valve leaflet. She underwent successful mitral valve replacement with a mechanical prosthesis 4 years after the initial diagnosis. To the best of our knowledge, an association between mitral valve regurgitation and Alagille syndrome has not been previously described. PMID- 17721852 TI - Right coronary ostial plasty without patch material. AB - Isolated right coronary ostial stenosis may require coronary revascularisation during an open-heart operation, especially during aortic valve replacement. We describe here a new method of right coronary ostial plasty without patch material. PMID- 17721853 TI - Implantation of a right heart assist device without a heart-lung machine in a patient with an acontractile right ventricle and HIT Type II. AB - A simple surgical technique to insert an RVAD without the use of a heart-lung machine and without full anticoagulation is described here. PMID- 17721854 TI - Postocardiotomy failure after Ross operation: implantation of intravascular flow pump through pulmonary autograft. AB - We report a case of a patient with severe aortic stenosis, who underwent replacement of the aortic valve as a Ross procedure. Postoperatively the patient suffered postcardiotomy failure. Despite prolonged reperfusion and other methods of circulatory support, the patient could not be weaned from cardiopulmonary bypass (CPB). Therefore, an Impella intravascular flow pump was implanted, which is technically easy and has good weaning attributes. For implantation, a vascular prosthesis was sewn to the ascending aorta and the microaxial flow pump was placed under echocardiographic guidance across the pulmonary autograft into the left ventricle. With this support, the patient could be weaned from CPB. The report evaluates the Impella microaxial hemopump as a device that is technically easy to implant with no injury to the pulmonary autograft in patients after Ross operation. Surgeons should consider the device as a short-term support in borderline indications. PMID- 17721855 TI - Intercostal bundle-splitting thoracotomy reduces chronic post-thoracotomy pain. AB - Intercostal nerve damage is the probable cause of chronic post-thoracotomy pain, but the precise mechanism is not known. To reduce this pain, we devised a simple method of rib spreading and closure (intercostal bundle-splitting thoracotomy), which avoids the intercostal nerve during thoracotomy, and then verified its effectiveness. The devised method appears to result in less chronic pain than the conventional method. PMID- 17721856 TI - Large thoracic wall hematoma following sternal reconstruction with transversal plate fixation after deep sternal wound infection. AB - We present the case of a 53-year-old male patient with a rare complication of a thoracic wall hematoma following thoracic wall reconstruction with transverse plate fixation and pectoralis advancement flaps. The patient could be subsequently discharged after surgical re-placement and an uneventful would healing. This case marks one of two complications occurring in a series of six patients treated for deep sternal wound infection with a combination of vacuum assisted therapy and plate fixation. PMID- 17721862 TI - Directed evolution of novel protein functions. AB - Directed evolution has been successfully used to engineer proteins for basic and applied biological research. However, engineering of novel protein functions by directed evolution remains an overwhelming challenge. This challenge may come from the fact that multiple simultaneously or synergistic mutations are required for the creation of a novel protein function. Here we review the key developments in engineering of novel protein functions by using either directed evolution or a combined directed evolution and rational or computational design approach. Specific attention will be paid to a molecular evolution model for generation of novel proteins. The engineered novel proteins should not only broaden the range of applications of proteins but also provide new insights into protein structure function relationship and protein evolution. PMID- 17721863 TI - Pulmonary artery/aorta ratio in simple screening for fetal outflow tract abnormalities during the second trimester. AB - OBJECTIVES: Congenital heart disease is associated with high mortality and morbidity rates, being the most life-threatening defect in the first month of postnatal life and accounting for approximately half of all childhood mortality from birth defects. Despite this, the prenatal detection rate for congenital outflow tract anomalies by ultrasound imaging is relatively low. The aim of this study was to establish a nomogram for the pulmonary artery/aorta (PA/AO) ratio measured in the three-vessel view plane. This ratio was investigated as a simple screening tool for congenital cardiac outflow tract abnormalities. METHODS: The study was a prospective evaluation of 966 singleton fetuses at 16-24 weeks of gestation and 46 fetuses with congenital cardiac outflow tract abnormalities. The diameters of the pulmonary artery and aorta were measured in the three-vessel view. The PA/AO ratio was calculated and a nomogram was constructed. The mean and 95% CI for the ratio were defined and the PA/AO ratios of cases with outflow tract abnormalities were plotted against the values for normal fetuses. RESULTS: The gestational age of the normal group ranged from 16 to 24 weeks, with a median of 19 weeks. The pulmonary artery diameter measured between 2.1 and 4.93 mm (mean, 3.3 mm) and the aorta measured between 2.1 and 5.2 mm (mean, 2.93 mm). The mean (SD) PA/AO ratio was 1.16 (0.18) (95% CI, 0.87-1.58; range 0.61-1.86; median, 1.14). For fetuses with outflow tract abnormalities, the median gestation was 19 weeks and 37/43 (86%) had a PA/AO ratio outside the 95% CI. CONCLUSIONS: The PA/AO ratio derived from measurements in the three-vessel view plane can be used as an initial screening tool for outflow tract anomalies and may have a sensitivity of up to 86%, with a 5% false-positive rate. PMID- 17721865 TI - Perinatal diagnosis of a lymphedema-distichiasis syndrome (LD). PMID- 17721864 TI - Neuronal LR11/sorLA expression is reduced in mild cognitive impairment. AB - OBJECTIVE: LR11 (aka sorLA) is a multifunctional neuronal receptor that binds apolipoprotein E and interacts with amyloid precursor protein to regulate amyloidogenesis. Reduced expression of LR11, as occurs in the brains of individuals with Alzheimer's disease (AD), increases amyloidogenesis, and variants in the gene that encodes LR11, SORL1, have recently been linked to risk for late-onset AD. In this study, we sought to determine whether reduced expression of LR11 occurs early in the disease process and whether protein levels in cortical neurons are associated with clinical and pathological changes in mild cognitive impairment (MCI), a condition that may represent prodromal AD. METHODS: A novel quantitative immunohistochemical approach was used to measure LR11 levels in brain tissue collected from subjects diagnosed antemortem with either no cognitive impairment, MCI, or AD from the Rush University Religious Orders Study. RESULTS: LR11 levels in MCI were intermediate between no cognitive impairment and AD. LR11 expression was heterogeneous in MCI, forming low- and high-level LR11 subgroups. MCI subjects with low LR11 were significantly more cognitively impaired than the high LR11 subjects. We also found a significant correlation between cognitive performance and LR11 levels across all clinical groups examined. There was no association between LR11 and plaque and tangle pathology. INTERPRETATION: Neuronal LR11 levels are reduced in prodomal AD. The correlation between LR11 expression and cognitive performance indicates that reduced LR11 levels reflect disease severity and may predict progression to AD in a subgroup of individuals with MCI. PMID- 17721866 TI - Prenatal ultrasonographic findings may be useful in predicting the prognosis of trisomy 18. AB - OBJECTIVE: This study was conducted to determine whether specific ultrasonographic findings in the prenatal period were associated with survival of children affected with trisomy 18. METHOD: Between October 1987 and July 2004, we collected 24 cases with trisomy 18. We investigated the relationship of prenatal ultrasonographic findings, gestational age at delivery, the Apgar score, the mode of delivery, and the neonatal treatment strategies, with survival time. RESULTS: 17 of the 24 neonates died within 1 month after birth (Group 1), 5 died within 12 months (Group 2), and 2 survived for more than 1 year (Group 3). Severe polyhydramnios was more frequent in group 1. In groups 2 and 3, the fluid in fetal stomach was visible in all cases. Severe cardiac anomalies were more frequent in group 1. In groups 2 and 3, all neonates were girl. CONCLUSION: Prenatal ultrasonographic findings associated with survival less than 1 month included severe polyhydramnios, absence of the fluid in the stomach, severe cardiac anomaly and male sex. PMID- 17721867 TI - Carbonate extraction process for the metabolic, isozymic and proteomic profiling of rose-scented geranium (Pelargonium sp.), a hyper-acidic plant. AB - Rose-scented geranium (Pelargonium sp.) is a valuable monoterpene-yielding plant. It has been well characterised phytochemically through the isolation of >270 secondary metabolites, however, there is hardly any biochemical or metabolic information concerning this plant. Initial attempts to investigate its metabolism failed to produce any enzyme activity in the tissue extracts prepared in routine extraction buffers owing to the intrinsic properties of the tissue matrix. It was recognised that cellular hyper-acidity (cell sap pH approximately 3.0) gave rise to very low protein levels in the extracts, thus prohibiting detection of activities of even primary metabolic enzymes that are usually abundantly present in plants. Tissue extraction in Tris solution without pH adjustment (as used for studies involving citrus and banana) led to little or no improvement. Therefore, a novel approach using sodium carbonate solution as an efficient extraction system for enzymes and proteins from the plant was studied. Functionality of the carbonate extraction has been demonstrated through its effectiveness, a several fold superior performance, in yielding protein, monitoring primary metabolism and secondary metabolic enzymes, and isozymic and polypeptide profiling. The process may also be helpful in the reliable analysis of other acidic plant tissues. PMID- 17721868 TI - Systolic and diastolic ventricular function in the normal and extra-embryonic venous clipped chicken embryo of stage 24: a pressure-volume loop assessment. AB - OBJECTIVES: Fluid mechanical forces affect cardiac development. In the chicken embryo, permanent obstruction of the right lateral vitelline vein by clipping reduces the mechanical load on the embryonic myocardium, which has been shown to induce a spectrum of outflow tract anomalies. Insight into the effects of this intervention on the mechanical function of the developing myocardium could contribute to a better understanding of the relationship between hemodynamics and cardiac morphogenesis. We aimed to explore the effects of clipping on intrinsic systolic and diastolic ventricular function at stage 24 in the chicken embryo METHODS: Cardiac pressure-volume relationships enable load-independent quantification of intrinsic ventricular systolic and diastolic properties. We determined ventricular function by pressure-volume loop analysis of in-ovo stage 24 chicken embryos (n = 15) 2 days after venous obstruction at 2.5 days of incubation (stage 17, venous clipped embryos). Control embryos (n = 15) were used for comparison. RESULTS: End-systolic volume was significantly higher in clipped embryos (0.36 +/- 0.02 microL vs. 0.29 +/- 0.02 microL, P = 0.002). End-systolic and end-diastolic pressure were also increased compared with control animals (2.93 +/- 0.07 mmHg vs. 2.70 +/- 0.08 mmHg, P = 0.036 and 1.15 +/- 0.06 mmHg vs. 0.82 +/- 0.05 mmHg, P < 0.001, respectively). No significant differences were demonstrated for other baseline hemodynamic parameters. Analysis of pressure volume relationships showed a significantly lower end-systolic elastance in the clipped embryos (slope of end-systolic pressure-volume relationship: 2.91 +/- 0.24 mmHg/microL vs. 7.53 +/- 0.66 mmHg/microL, P < 0.005) indicating reduced contractility. Diastolic stiffness was significantly increased in the clipped embryos (slope of end-diastolic pressure-volume relationship: 1.54 +/- 0.21 vs. 0.60 +/- 0.08, P < 0.005), indicating reduced compliance. CONCLUSION: Venous obstruction apparently interferes with normal myocardial development, resulting in impaired intrinsic systolic and diastolic ventricular function. These changes in ventricular function may precede morphological derangements observed in later developmental stages. PMID- 17721871 TI - Comments on 'Confidence intervals for a ratio of binomial proportions based on paired data' by D. G. Bonett and R. M. Price, Statistics in Medicine 2006; 25:3039-3047. PMID- 17721870 TI - New Doppler index for prediction of perinatal brain damage in growth-restricted and hypoxic fetuses. AB - OBJECTIVE: To evaluate the new vascular score, hypoxia index (HI), in the prediction of sonographically detected structural brain lesions in neonates within the first week after delivery of growth-restricted fetuses. METHODS: This prospective study included 29 growth-restricted fetuses delivered between 31 and 40 gestational weeks. Doppler umbilical artery (UA) and middle cerebral artery (MCA) resistance indices (RI) were recorded at 48-h intervals for at least 2 weeks before delivery. The cerebroumbilical ratio (C/U ratio = MCA-RI/UA-RI) and the HI (the sum of the daily reductions in C/U ratio, i.e. percentage below the cut-off value of 1, over the period of observation) were calculated. After delivery, neonatal outcome was evaluated according to obstetric parameters and ultrasound examinations of the brain. Doppler indices, C/U ratio and HI, as well as neonatal clinical and biochemical parameters, were tested as potential predictors of brain lesions using the C4.5 data-mining algorithm. RESULTS: Neonatal brain lesions were detected in 13 growth-restricted fetuses. Of all the parameters tested by the C4.5 data-mining algorithm, only HI was identified as a predictor of neonatal brain lesions. HI also showed better correlation with neonatal biochemical parameters, such as umbilical venous partial pressure of oxygen and umbilical venous pH, compared with the C/U ratio. CONCLUSIONS: HI, which takes into account cumulative oxygen deficit, could significantly improve the prediction of a poor neurological outcome in pregnancies complicated by growth restriction and hypoxia. PMID- 17721872 TI - Gene therapy legislation in The Netherlands. AB - Several regulatory organisations are involved in the assessment of clinical gene therapy trials involving genetically modified organisms (GMOs) in The Netherlands. Medical, ethical and scientific aspects are, for instance, evaluated by the Central Committee on Research Involving Human Subjects (CCMO). The Ministry of Housing, Spatial Planning and the Environment (VROM) is the competent authority for the environmental risk assessment according to the deliberate release Directive 2001/18/EC. A Gene Therapy Office has been established in order to streamline the different national review processes and to enable the official procedures to be completed as quickly as possible. Although the Gene Therapy Office improved the application process at the national level, there is a difference of opinion between the EU member states with respect to the EU Directive according to which gene therapy trials are assessed, that urges for harmonisation. This review summarises the gene therapy legislation in The Netherlands and in particular The Netherlands rationale to follow Directive 2001/18/EC for the environmental risk assessment. PMID- 17721873 TI - Randomization with a posteriori constraints: description and properties. AB - The use of randomization for assigning patients to treatment groups in clinical trials is firmly acknowledged as providing the best quality results. Two standard methods are used in order to achieve well-balanced groups with respect to prognostic factors (i.e. factors influencing the disease outcome): stratification and minimization. Stratification is recommended when the number of strata is not too high--otherwise, minimization is preferred. However, minimization may compromise blinding (since the search for balance is performed a priori) and, furthermore, use of the technique has been questioned by the European Agency for the Evaluation of Medicinal Products. We have developed a new procedure for adaptive randomization, which we have named 'randomization with a posteriori constraints'. By using a search for balance a posteriori, this procedure ensures that patient groups are similar with respect to prognostic factors while being less vulnerable to selection bias. The aim of this work was to describe the new method and to compare it (using simulations) with stratification and minimization. In the case of trials with few prognostic factors, the recourse to minimization or 'randomization with a posteriori constraints' does not appear to be useful. In such a context, stratification has suitable properties and its simplicity of implementation encourages its use. However, when the number of prognostic factors is higher, 'randomization with a posteriori constraints' is less predictable than minimization and the chance of imbalance is lower than for stratification. In conclusion, 'randomization with a posteriori constraints' with an adequate threshold seems to be a good compromise between minimization and stratification. PMID- 17721874 TI - Gene therapy clinical trials worldwide to 2007--an update. AB - To date, over 1340 gene therapy clinical trials have been completed, are ongoing or have been approved worldwide. In 1997 we set up a database to bring together global information on gene therapy clinical trials as comprehensively as possible. The data are compiled and regularly updated from official agency sources, published literature, conference presentations and posters and from information kindly provided by investigators or trial sponsors themselves. This review updates our descriptive overview of the data in 2004 1, presenting our analysis of the clinical trials that, to the best of our knowledge, have been or are being performed worldwide. As of July 30 2007, we have stored entries on 1309 trials in 28 countries. We have analyzed the geographical distribution of trials, the disease indications (or other reasons) for trials, the proportions to which different vector types are used, and which genes have been transferred. Details of the analyses presented, and our interactive, searchable database can be found on The Journal of Gene Medicine Gene Therapy Clinical Trials Worldwide website at: http://www.wiley.co.uk/genmed/clinical. PMID- 17721875 TI - Gene therapy in The Netherlands: highlights from the Low Countries. AB - Gene therapy is an active research area in The Netherlands and Dutch scientists involved in fundamental and clinical gene therapy research significantly contribute to the progresses made in this field. This ranges from the establishment of the 293, 911 and PER.C6 cell lines, which are used worldwide for the production of replication-defective adenoviral vectors, to the development of targeted viral vectors and T lymphocytes as well as of non-viral vectors. Several milestones have been achieved in Dutch clinical gene therapy trials, including the first treatment worldwide of patients with adenosine deaminase deficiency with genetically corrected hematopoietic stem cells in collaboration with French and British scientists. Until now, about 230 patients with various diseases have been treated with viral and non-viral gene therapy in this country. Ongoing and upcoming Dutch clinical trials focus on the translation of new developments in gene therapy research, including the restoration of genetic defects other than SCID, and the use of oncolytic adenoviruses and targeted T cells for the treatment of cancer. The growing commercial interest in Dutch clinical gene therapy is reflected by the involvement of two Dutch companies in ongoing trials as well as the participation of Dutch clinical centres in large phase III international multicenter immuno-gene therapy trials on prostate cancer sponsored by an American company. Translational gene therapy research in The Netherlands is boosted at a governmental level by the Dutch Ministry of Health via a dedicated funding programme. This paper presents an overview on milestones in Dutch basic gene therapy research as well as on past, present and future clinical gene therapy trials in The Netherlands. PMID- 17721876 TI - An intriguing "silent" mutation and a founder effect in antiquitin (ALDH7A1). AB - Recently, alpha-aminoadipic semialdehyde (alpha-AASA) dehydrogenase deficiency was shown to cause pyridoxine-dependent epilepsy in a considerable number of patients. alpha-AASA dehydrogenase deficiency is an autosomal recessive disorder characterized by a neonatal-onset epileptic encephalopathy in which seizures are resistant to antiepileptic drugs but respond immediately to the administration of pyridoxine (OMIM 266100). Increased plasma and urinary levels of alpha-AASA are associated with pathogenic mutations in the alpha-AASA dehydrogenase (ALDH7A1/antiquitin) gene. Here, we report an intriguing "silent" mutation in ALDH7A1, a novel missense mutation and a founder mutation in a Dutch cohort (10 patients) with alpha-AASA dehydrogenase deficiency. PMID- 17721877 TI - The Unified Parkinson's Disease Rating Scale: validation study of the mentation, behavior, and mood section. AB - The objective of this study was to examine the validity of the mentation, behavior, and mood items included in Part I of the Unified Parkinson's Disease Rating Scale (UPDRS) and to assess its usefulness to screen for dementia, psychosis, depression, and apathy. A consecutive series of 168 patients with PD were assessed by neurologists with the UPDRS, and by psychiatrists using a comprehensive neuropsychiatric evaluation blind to each other's ratings. ROC analysis demonstrated that a score of 2 or greater on the intellectual impairment item of the UPDRS had 60% sensitivity and 92% specificity to detect dementia, as diagnosed with DSM-IV criteria. When a score of 23 or lower on the MMSE was included as an additional classification variable, the sensitivity increased to 85%. A score of 2 or greater on the thought disorder item had 43% sensitivity and 92% specificity to detect psychotic symptoms (delusions or hallucinations). A score of 2 or greater on the depression item had 77% sensitivity and 82% specificity to detect major depression as diagnosed with DSM-IV criteria. Finally, a score of 2 or greater on the motivation/initiative item had 73% sensitivity and 65% specificity to detect apathy, as diagnosed with a standardized criteria. When the sample was divided into mild (i.e. Hohen-Yahr stages I and II) versus moderate-severe PD (i.e. Hohen-Yahr stages III-V), findings remained unchanged, except that the UPDRS show unacceptably low accuracy to detect psychosis in mild PD. The mentation, behavior, and mood section of the UPDRS is an adequate screen for depression and apathy, and has adequate sensitivity to detect dementia when combined with the Mini-Mental State Exam, but has low sensitivity to detect psychosis. PMID- 17721878 TI - Monitoring denitrification by pH-Stat titration. AB - An improved pH-stat titrimetric procedure was developed, validated, and extensively applied to monitor biological heterotrophic denitrification in a lab scale sequencing batch reactor (SBR). So far, titrimetric procedures were not successful in monitoring denitrification processes in full-scale wastewater (WW) treatment plants, mainly because the stoichiometric ratio between proton production and nitrate reduction is highly variable due to variability of both biomass and influent WW characteristics. In this article, a new titration procedure is proposed where a simple calibration step is performed before each experimental test. This procedure allows for the assessment of (i) nitrate content in a sample of mixed liquor; (ii) the maximum denitrification rate of sludge when fed on acetate; and (iii) the denitrification potential (DNP) of different substrates. As for (i), validation by comparison with spectrophotometric measures indicated an average discrepancy of less than 3% on more than 40 samples; as for (ii) and (iii) collected values compared well with literature data. The titrimetric method proposed here is also capable of assessing the biomass anoxic yield in a very simple way, since it does not require any analytical nitrate determination. According to the results of this experimentation, titrimetry appeared to be a simple, inexpensive, and powerful tool for monitoring and operating denitrification processes in WW treatment plants. PMID- 17721880 TI - Understanding topological symmetry: a heuristic approach to its determination. AB - An algorithm based on heuristic rules for topological symmetry perception of organic structures having heteroatoms, multiple bonds, and any kind of cycle, and configuration, is presented. This algorithm identifies topological symmetry planes and sets of equivalent atoms in the structure, named symmetry atom groups (SAGs). This approach avoids both the need to explore the entire graph automorphism groups, and to encompass cycle determination, resulting in a very effective computer processing. Applications to several structures, some of them highly symmetrical such as dendrimers, are presented. PMID- 17721879 TI - Excited states of GFP chromophore and active site studied by the SAC-CI method: effect of protein-environment and mutations. AB - Excited states of fluorescent proteins were studied using symmetry-adapted cluster-configuration interaction (SAC-CI) method. Protein-environmental effect on the excitation and fluorescence energies was investigated. In green fluorescent protein (GFP), the overall protein-environmental effect on the first excitation energy is not significant. However, glutamine (Glu) 94 and arginine (Arg96) have the red-shift contribution as reported in a previous study (Laino et al., Chem Phys 2004, 298, 17). The excited states of GFP active site (GFP-W22 Ser205-Glu222-Ser65) were also calculated. Such large-scale SAC-CI calculations were performed with an improved code containing a new algorithm for the perturbation selection. The SAC-CI results indicate that a charge-transfer state locates at 4.19 eV, which could be related to the channel of the photochemistry as indicated in a previous experimental study. We also studied the excitation and fluorescence energies of blue fluorescent protein, cyan fluorescent protein, and Y66F. The SAC-CI results are very close to the experimental ones. The protonation state of blue fluorescent protein was determined. Conformation of cyan fluorescent protein indicated by the present calculation agrees to the experimentally observed structure. PMID- 17721881 TI - Comparison of nonbreast cancer incidence, survival and mortality between breast screening program participants and nonparticipants. AB - Comparisons of cancer mortality between users and nonusers of screening are potentially biased because of the effects of self-selection. Previous studies of breast screening have found that individuals likely to participate have lower breast cancer mortality than those unlikely to participate. This study compares the incidence, survival and mortality for all cancer types other than breast between participants and nonparticipants in a service screening mammography program. British Columbian females having their first mammogram between the ages of 40 and 79 and the years 1988 and 2004 were identified as a cohort of "participants". Person-years of follow-up of participants were aggregated by age and year. Nonparticipant person-years were obtained by subtraction from the total female population. Cancer diagnoses other than breast were identified for participants and nonparticipants. Age, calendar year, and income adjusted relative risks of cancer incidence were estimated from generalized additive models with Poisson errors. Hazard ratios were estimated by Cox regression. Observed cancer mortality in participants was compared with expected mortality generated from nonparticipant incidence and survival rates. Incidence rates of cancer showed a mixed relationship with some elevated, some decreased and others similar to nonparticipant rates. Cancer survival was higher among participants for most cancer types, with an overall hazard ratio of 0.76 (0.73-0.79). Observed mortality in participants was less than expected for most cancers, with an overall mortality ratio of 0.60 (0.58-0.62). The general cancer experience of screening program participants is different from that of the general population. PMID- 17721882 TI - The metastatic T-cell hybridoma antigen/P-selectin glycoprotein ligand 1 is required for hematogenous metastasis of lymphomas. AB - Using variants of the murine BW5147 lymphoma cell-line, we have previously identified 3 monoclonal antibodies (MAbs) that discriminate between metastatic and nonmetastatic BW5147-derived T-cell hybridomas and lymphomas, as well as BW5147-unrelated T-lymphomas. These MAbs were reported to recognize an identical membrane-associated sialoglycoprotein, termed "metastatic T-cell hybridoma antigen" (MTH-Ag). Here, we document that the expression pattern of the MTH-Ag on metastatic and nonmetastatic BW5147 variants correlates with that of the P selectin glycoprotein ligand 1 (PSGL-1), a sialomucin involved in leukocyte recruitment to sites of inflammation. Moreover, the MAbs against the MTH-Ag recognize PSGL-1 when it is transfected in MTH-Ag-negative BW5147 variants, suggesting that the MTH-Ag is PSGL-1. Overexpression of MTH-Ag/PSGL-1 in MTH-Ag negative BW5147 variants did not affect their in vivo malignancy. Yet, down regulation of MTH-Ag/PSGL-1 expression on metastatic, MTH-Ag-positive BW5147 variants, using an RNA interference (RNAi) approach, resulted, in a dose dependent manner, in a significant reduction of liver and spleen colonization and a delay in mortality of the recipient mice upon intravenous inoculation. Collectively, these results demonstrate that, although MTH-Ag/PSGL-1 overexpression alone may not be sufficient for successful dissemination and organ colonization, MTH-Ag/PSGL-1 plays a critical role in hematogenous metastasis of lymphoid cancer cells. PMID- 17721883 TI - Polymeric and low molecular mass efflux pump inhibitors for oral drug delivery. AB - Transmembrane located transporter proteins can be responsible for the low bioavailability of orally administered drugs. Drug delivery systems which can overcome this barrier caused by efflux pumps are therefore highly on demand. Within the current review, intestinal located efflux transporters, methods to identify efflux pump substrates and inhibitors as well as strategies to minimize efflux pump mediated transport of drugs are discussed. Methods include in silico screening, transport and accumulation studies and monitoring of the ATPase activity. An emphasis has been placed on efflux pump inhibitors including low molecular mass inhibitors such as cyclosporine, PSC833 or KR30031 and polymeric inhibitors such as myrj, thiomers and cremophor EL. Also formulation approaches to circumvent intestinal segments with high efflux pump expression are briefly addressed. PMID- 17721884 TI - Volume change measurements of rice by environmental scanning electron microscopy and stereoscopy. AB - The measurement of volume change, which is induced by changing the relative humidity, is performed on rice by using environmental scanning electron microscope (ESEM) and stereoscopy techniques. The typical DeltaV% approximately RH curve of rice in both sorption and desorption can be categorized into three regions: low, intermediate, and high dependence on relative humidity from low- to high-relative humidity. The volume changes faster for rice samples with lower crystallinity, which is because the amorphous component is easier to absorb moisture than the crystalline component. The volume change behavior in various relative humidity environments is comparable with rice isotherm curve in sorption process though discrepancies exist in desorption, which are thought to be the presence of small pores and microstructure changes at high relative humidity. The volume in the desorption branch is less than that in the sorption branch at the same relative humidity, which can be attributed to the collapse of interior structures, existence of small pores, surface topography loss, and amylose leach. PMID- 17721886 TI - Osteopontin overexpression in breast cancer: knowledge gained and possible implications for clinical management. AB - Osteopontin (OPN) is a secreted protein that is overexpressed in a number of human cancers, and has been associated with increased metastatic burden and poor prognosis in breast cancer patients. The OPN protein contains several conserved structural elements including heparin- and calcium-binding domains, a thrombin cleavage site, a CD44 binding site, and two integrin-binding sites. Experimental studies have shown that the ability of OPN to interact with a diverse range of factors, including cell surface receptors (integrins, CD44), secreted proteases (matrix metalloproteinases, urokinase plasminogen activator), and growth factor/receptor pathways (TGFalpha/EGFR, HGF/Met) is central to its role in malignancy. These complex signaling interactions can result in changes in gene expression, which ultimately lead to alterations in cell properties involved in malignancy such as adhesion, migration, invasion, enhanced tumor cell survival, tumor angiogenesis, and metastasis. Therefore, OPN is not merely associated with cancer, but rather it plays a multi-faceted functional role via complex molecular cross-talk with other factors. This review will focus on the role of OPN in breast cancer, in particular on the malignancy-promoting aspects of OPN that may reveal opportunities for new approaches to the clinical management of breast cancer. PMID- 17721887 TI - A spectroscopic study of the reduction of geometrically restrained viologens. AB - A small series of N,N'-dimethyl-4,4'-bipyridinium dication derivatives (commonly known as viologens) has been synthesized and fully characterized; a short dialkoxy tether attached at the 3,3'-positions is used to alter the central dihedral angle. These angles were determined by both single-crystal X-ray diffraction and by computational studies made for the dication, radical cation, and neutral species in a solvent reservoir. The dihedral angle derived for the dication controls the first reduction potential, whereas the geometry of the resultant pi-radical cation determines the magnitude of the second reduction potential. The optical absorption spectra recorded for the various species, and especially those of the radical cations, and the EPR spectral parameters of the pi-radical cations also depend on the molecular geometry. In particular, the central dihedral angle influences the spin density distribution around the aromatic nucleus and, by way of comparison to the parent viologen, it has been possible to resolve the angle dependence from the inherent inductive effect of the strap. These results are considered in terms of the degree of electronic communication between the two aromatic rings, as controlled by the length of the tether. PMID- 17721885 TI - Overexpression of Akt1 upregulates glycogen synthase activity and phosphorylation of mTOR in IRS-1 knockdown HepG2 cells. AB - Insulin receptor substrate (IRS) proteins are important docking proteins in mediating the insulin signaling cascade. We have investigated the effect of short interfering RNA (siRNA) mediated knockdown of IRS-1 on insulin signaling cascade in primary human hepatocellular carcinoma HepG2 cell line and HepG2 cells overexpressing Akt1/PKB-alpha (HepG2-CA-Akt/PKB). IRS-1 knockdown in both cell lines resulted in reduction of insulin stimulated Akt1 phosphorylation at Ser 473. In parental HepG2 cells, IRS-1 knockdown resulted in reduction (ca. 50%) in the basal level of phosphorylated mTOR (Ser 2448) irrespective of insulin treatment. In contrast, HepG2-CA-Akt/PKB cells showed an upregulation in the basal level of phosphorylated mTOR (Ser 2448) (ca. 40%). Insulin mediated phosphorylation of mTOR was reduced. IRS-1 knockdown also reduced the cell proliferation of parental HepG2 cells by ca. 30% in the presence/absence of insulin, whereas in HepG2-CA-Akt/PKB the cell proliferation was reduced by 15% and treatment of insulin further reduced it to ca. 50% (vs. control). IRS-1 knockdown also reduced the glycogen synthase (GS) activity in parental HepG2 cells, however, it was upregulated in HepG2-CA-Akt/PKB cells. These results suggest that knockdown of IRS-1 abolished basal as well as insulin mediated phosphorylation/activity of proteins involved in cell proliferation or glycogen metabolism in the parental Hep2 cells. IRS-1 knockdown in cells overexpressing constitutively active Akt1/PKB-alpha either did not change or upregulated the basal levels of phosphorylated/active proteins. However, insulin mediated response was either not altered or downregulated in these cells. PMID- 17721888 TI - Porous metal oxides as gas sensors. AB - Semiconducting metal oxides are frequently used as gas-sensing materials. Apart from large surface-to-volume ratios, well-defined and uniform pore structures are particularly desired for improved sensing performance. This article addresses the role of some key structural aspects in porous gas sensors, such as grain size and agglomeration, pore size or crack-free film morphology. New synthesis concepts, for example, the utilisation of rigid matrices for structure replication, allow to control these parameters independently, providing the opportunity to create self-diagnostic sensors with enhanced sensitivity and reproducible selectivity. PMID- 17721889 TI - 2D supramolecular self-assembly of binary organic monolayers. PMID- 17721890 TI - Enantiopure double-helical phenylene ethynylene cyclophynes with the 2,2' binaphthyl template. AB - New types of enantiopure compounds were synthesized to gain better insight into the structural features of phenylene ethynylene cyclophynes. Besides the previously obtained meta-substituted arylene ethynylenes, 1, ortho-connected phenylene ethynylene units were incorporated to give cyclophynes with ortho/meta and ortho/ortho connection modes, 2 and 3. Furthermore, a diphenylethyne component was also accommodated in 4. Both ab initio calculations and NMR spectra suggest a large amount of strain for 2 but less strain for 3 and 1 a, the latter having the smallest ring size among cyclophynes with the meta/meta connection mode. The CD spectra of 2 and 3 showed a characteristic shoulder at around 340 nm, similar to the case of 1 a. This implies that the aromatic acetylene bonds cross over each other in the double-helical structure. These results indicate that chirality information is useful for probing the persistency of molecular shape. PMID- 17721891 TI - Platinum-catalyzed multistep reactions of indoles with alkynyl alcohols. AB - PtCl2 effectively catalyzes the multistep reaction of N-methyl indole (1 a) with pent-3-yn-1-ol (2 a) in THF at room temperature for 2 h to give indole derivative 3 a, which contains a five-membered cyclic ether group at C3 in 93% yield. Under similar reaction conditions, various substituted N-methyl indoles 1 b-h and indole (1 i) reacted efficiently with 2 a to afford the corresponding indole derivatives 3 b-h and 3 i in 48-91 and 72% yields. The results showed that N methyl indoles with electron-donating substituents were more reactive affording higher product yields than those with electron-withdrawing groups. Likewise, various substituted but-3-yn-1-ols 2 b-e and other longer chain alkynyl alcohols 2 f-i also underwent a cyclization-addition reaction with N-methyl indole (1 a) to provide the corresponding cyclization-addition products 3 j-m and 3 a, 3 j, and 3 n-o in good to excellent yields. The present platinum-catalyzed cyclization addition reaction can be further extended into N-methyl pyrrole. Mechanistically, the catalytic reaction proceeds by an intramolecular hydroalkoxylation of alkynyl alcohol to afford cyclic enol ether followed by the addition of the C--H bond of indole to the unsaturated moiety of cyclic enol ether providing the final product. Experimental evidence to support this proposed mechanism is provided. PMID- 17721892 TI - Iterative synthesis of spacered glycodendrons as oligomannoside mimetics and evaluation of their antiadhesive properties. AB - Dendrimer chemistry is an attractive concept for mimicry of the highly branched character of the bioactive carbohydrates found as part of a cell's sugar coat, called the glycocalyx. Glycodendrimers have thus been used to study biological processes occurring on cell surfaces, such as bacterial adhesion. This paper details a new approach in glycodendrimer synthesis, in which a 3,6-diallylated carbohydrate is utilised as core molecule, hydroboration-oxidation is the activating step, and glycosylation with branched and unbranched sugar trichloroacetimidates is used for dendritic growth. To obtain pure dendritic pseudo-tri- and -heptasaccharides in good yields, radical addition of mercaptoethanol to peripheral double bonds was also evaluated with great success. A collection of six new hyperbranched glycodendrons was tested for their potential as inhibitors of type 1 fimbriae-mediated bacterial adhesion in an ELISA and the results were interpreted with regard to sugar valency and spacer characteristics. PMID- 17721893 TI - Synthesis and metal complexes of chiral c(2)-symmetric diamino-bisoxazoline ligands. AB - A synthetic route to tetradentate chiral N(4) ligands has been developed with the aim to study the potential of corresponding iron and manganese complexes as catalysts for enantioselective epoxidation. These ligands, which contain two oxazoline rings and two trialkylamino groups as coordinating units, are readily prepared in enantiomerically pure form by the reaction of chiral 2 chloromethyloxazolines with achiral N,N'-dimethylethane-1,2-diamine or chiral (R,R)-N,N'-dimethylcyclohexane-1,2-diamine. The ligands derived from N,N' dimethylethane-1,2-diamine reacted with anhydrous metal halides MnCl(2) and FeCl(2) in a stereoselective manner to give octahedral mononuclear complexes that have the general formula Delta-[(L)MCl(2)]. In contrast, the ligands derived from N,N'-dimethylcyclohexane-1,2-diamine formed complexes with different coordination modes depending on the diastereomer employed: in one case the metal ion was found to be pentacoordinate, in the other case a hexacoordinated complex was observed. The structure of a series of Fe and Mn complexes was determined by X-ray analysis. The coordination chemistry of these ligands was further studied by X ray and NMR analyses of the diamagnetic isostructural complexes [(L)ZnCl(2)]. Analogous ionic complexes, which were prepared by removing chloride with silver trifluoromethanesulfonate or hexafluoroantimonate, were tested as catalysts for the epoxidation of olefins. PMID- 17721894 TI - Characterization of the interplay between the main factors contributing to lipoplex-mediated transfection in cell cultures. AB - Transfection efficiency of lipoplex-mediated gene delivery is multifactorial. However, the mode of interaction between the factors which affect transfection is not fully understood. To help fill this deficiency we evaluated the effect of the interplay between several variables that affect transfection efficiency in cell cultures. For this, we applied the Analysis of Variance Model with Fixed Effects and Repeated Measures to assess the data. The variables studied include: two different genes, Luc, and human growth hormone (hGH), in three different plasmids (two of which contain the luciferase (Luc) gene, but different promoter-enhancer regions (CMV and H19) and one plasmid coding hGH with a S16 promoter); three topoisoforms of pDNA (supercoiled (SC), open circular (OC), and closed circular (CC)); three cationic lipid compositions, all based on the monocationic lipid DOTAP (100% DOTAP, DOTAP/DOPE 1 : 1, and DOTAP/cholesterol 1 : 1, all ratios are mole ratios); two DNA-/L+ charge ratios (0.2 and 0.5); and two cell lines (NIH 3T3 and MBT-2). Our statistical analysis confirmed that the cell type, the gene used for transfection, the promoter type, the type of helper lipid, and DNA /DOTAP+ charge ratio, all affect transfection efficiency in a statistically significant manner. The most efficient lipoplex formulation in both cell lines was that based on DOTAP (without helper lipid), having CC plasmid DNA. We suggest that for obtaining the most transfection-efficient lipoplex one should select the best topoisoform of pDNA for each particular cell type, and complex it with cationic liposomes having optimal lipid composition. PMID- 17721895 TI - Unbiased selection of bone marrow derived cells as carriers for cancer gene therapy. AB - BACKGROUND: There is currently great interest in development of cell-based carriers for delivery of viral vectors to metastatic tumors. To date, several cell carriers have been tested based largely upon their predicted tumor localizing properties. However, cell types may exist which can be mobilized from the circulation by a tumor which have not yet been identified. Here we use an unbiased screen of bone marrow (BM) cells to identify cells which localize to tumors and which might serve as effective candidate cell carriers without any prior prediction or selection. METHODS: Unsorted BM cells from green fluorescent protein (GFP)-transgenic donor mice were adoptively transferred into C57Bl/6 mice bearing pre-established subcutaneous B16 melanoma tumors. Forty-eight hours and eight days later, tumors, organs and blood were analyzed for GFP-expressing cells by flow cytometry. The phenotype of GFP cells in organs was determined by co staining with specific cell surface markers. RESULTS: CD45(+) hematopoietic cells were readily detected in tumor, spleen, bone marrow, blood and lung at both time points. Within these CD45(+) cell populations, preferential accumulation in the tumor was observed of cells expressing Sca-1, c-kit, NK1.1, Thy1.2, CD14, Mac-3 and/or CD11c. Lymphodepletion increased homing to spleen and bone marrow, but not to tumors. CONCLUSIONS: We have used an in vivo screen to identify populations of BM-derived donor cells which accumulate within tumors. These studies will direct rational selection of specific cell types which can be tested in standardized assays of cell carrier efficiency for the treatment of metastatic tumors. PMID- 17721896 TI - Oseltamivir-induced delirium in a geriatric patient. PMID- 17721899 TI - Gastrointestinal stromal tumors mimicking gynecological masses on ultrasound: a report of two cases. AB - Gastrointestinal stromal tumors (GISTs) are among the most common mesenchymal tumors of the gastrointestinal tract. Diagnosis of GIST on ultrasound examination can be difficult because of their similarity in appearance to gynecological neoplasms. We present two cases of GIST originating from the small bowel and the stomach, which were preoperatively misdiagnosed as a uterine leiomyoma and an ovarian tumor, respectively. The ultrasonographic differential diagnosis of these pelvic masses is discussed. PMID- 17721898 TI - Work-related physical activity and the risk of dementia and Alzheimer's disease. AB - BACKGROUND: Leisure-time physical activity has been related with a reduced risk of dementia and Alzheimer's disease (AD). The effects of occupational and commuting physical activity (physical activity at work and on the way to work) on cognitive health are still unclear. This study aimed to clarify the association between work-related physical activity and dementia/AD. METHODS: Participants of the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study were derived from random, population-based samples previously studied in a survey carried out in 1972, 1977, 1982, or 1987. After an average follow-up of 21 years, 1449 individuals (73%) aged 65 to 79 years participated in the re-examination in 1998. RESULTS: Neither occupational [Odds Ratio (OR) 1.45; 95% Confidence Intervals (CI) 0.66-3.17] nor commuting physical activity (OR 0.46; 95% CI 0.10-2.17) were associated with the risk of dementia or AD after adjustments for age, sex, education, follow-up time, locomotor symptoms, main occupation during life, income at midlife, leisure-time physical activity, other subtype of work-related physical activity, ApoE genotype, vascular disorders and the smoking status. There were also no interactions between work-related physical activity and the ApoE epsilon4 genotype, leisure-time physical activity or sex. CONCLUSIONS: In this study, work-related physical activity was not found to be sufficient to protect against dementia and AD later in life. The lack of effect might be partly due to a residual confounding. Nevertheless, physical activity during leisure time may be beneficial even for people who are physically active at work or when commuting. PMID- 17721900 TI - Equity in health and health care in a decentralised context: evidence from Canada. AB - The impact of administrative decentralisation on equity in health and health care is an important unresolved issue in the health policy debate. Predictions from the limited theoretical literature and the relevant empirical research are both insufficient to draw any firm conclusions. Many countries are nevertheless experimenting with decentralisation policies in the absence of research evidence. This paper presents an exploratory empirical analysis of decentralisation by investigating the spatial dimensions of health-related equity in Canada, a highly decentralised setting. Using data from the 2001 Canadian Community Health Survey, we apply a decomposition method of the Concentration Index to explore whether income-related inequalities in health and inequities in the use of health care are more likely to be due to gaps between rich and poor Canadian provinces rather than to differences between rich and poor individuals within them. The results show that within area variation is the most important source of income-related health inequality, while income-related inequities in health care use are mostly driven by differences between provinces. PMID- 17721901 TI - Instrumental activities of daily living in the screening of dementia in population studies: comment on Castilla-Rilo et al. (2007). PMID- 17721903 TI - Neutral desorption sampling coupled to extractive electrospray ionization mass spectrometry for rapid differentiation of biosamples by metabolomic fingerprinting. AB - It is of increasing interest and practical importance to develop convenient methods based on mass spectrometry for high-throughput analyses of biological samples. This is usually difficult because of the complex matrix and ion suppression effects. Generation of ions at ambient conditions is a promising solution to these problems because the sample is easily accessible and the ion suppression effect is reduced significantly. A new method for rapid on-line detection of metabolic markers in complex biological samples is described here. It combines atmospheric pressure desorption sampling by a gentle stream of air or nitrogen with extractive electrospray ionization (EESI) and mass spectrometric analysis. The resulting mass spectral fingerprints are shown to be able to detect spoilage of meat even in the frozen (-20 degrees C) state and the contamination of spinach by E. coli, and to identify metabolites and contaminants on human skin within seconds, in an on-line and high-throughput fashion. Typical molecular markers are identified using MS/MS data and by comparison with reference compounds. Differences between closely related samples are easily visualized by using principal component analysis (PCA) of the mass spectra data. The detection limit achieved is 10 fg/cm2 (S/N = 3) for histamine on the surface of frozen meat. The technique reported here shows potential for more advanced applications in multiple disciplines, including food regulation, homeland security, in vivo metabolomics, and clinical diagnosis. PMID- 17721905 TI - Estimation of ROC curves based on stably distributed biomarkers subject to measurement error and pooling mixtures. AB - Additive measurement errors and pooling design are objectively two different issues, which have been separately and extensively dealt with in the biostatistics literature. However, these topics usually correspond to problems of reconstructing a summand's distribution of the biomarker by the distribution of the convoluted observations. Thus, we associate the two issues into one stated problem. The integrated approach creates an opportunity to investigate new fields, e.g. a subject of pooling errors, issues regarding pooled data affected by measurement errors. To be specific, we consider the stated problem in the context of the receiver operating characteristic (ROC) curves analysis, which is the well-accepted tool for evaluating the ability of a biomarker to discriminate between two populations. The present paper considers a wide family of biospecimen distributions. In addition, applied assumptions, which are related to distribution functions of biomarkers, are mainly conditioned by the reconstructing problem. We propose and examine maximum likelihood techniques based on the following data: a biomarker with measurement error; pooled samples; and pooled samples with measurement error. The obtained methods are illustrated by applications to real data studies. PMID- 17721906 TI - On the search for glycated lipoprotein ApoA-I in the plasma of diabetic and nephropathic patients. AB - The analysis of plasma samples from healthy, diabetic and nephropathic subjects was carried out by 2D gel electrophoresis. This approach shows clear differences among the three classes of subjects. In the case of diabetic and nephropathic patients intense spots appear. Their enzymatic digestion followed by matrix assisted laser desorption ionization/mass spectrometry (MALDI/MS) analysis shows that an overexpression of unglycated and glycated ApoA-I is present in both pathological states. Interestingly, this trend is also observed for the retinol binding protein (RBP). The data obtained can be relevant to assess possible risks associated either with the glycation level of ApoA-I or with the overexpression of RBP. In fact, in the former case possibly a different functionality of the glycated protein is to be expected, reflecting a different efficiency in cholesterol transport. In the latter case, the increase of RBP level can be related to the overweight of the diabetic subjects under investigation: it is known that obesity leads to RBP overexpression. In the case of nephropathic patients, the RBP level increases in parallel with serum creatinin. PMID- 17721907 TI - Kernel estimation of risk surfaces without the need for edge correction. AB - Kernel estimates of relative risk surfaces can be used to examine the geographical variation of disease risk. These surfaces can be expressed as ratios of bivariate kernel density estimates constructed from case and control data, but care must be taken to avoid excessive bias at the boundaries of the region under study. It is possible to correct this bias, without the complications of explicit edge correction, through the use of a specific smoothing regimen. PMID- 17721908 TI - Color Doppler ultrasound of spiral artery blood flow for prediction of hypertensive disorders and intra uterine growth restriction: a longitudinal study. AB - OBJECTIVE: To construct reference ranges for spiral artery (SA) flow velocities and examine the possibility to predict intra uterine growth restricted (IUGR) fetuses, pregnancy-induced hypertension (PIH) and/or preeclampsia. METHODS: Spiral artery flow velocity measurements were performed using Color Doppler between 11 to 13 + 6, between 14 to 17 + 6 and between 18 to 24 weeks of gestation, each measurement was performed twice. Spiral artery flow velocities were analyzed with multilevel modeling: individual regression curves were estimated and combined to obtain the reference intervals for SA flow velocities in normal pregnancies. Mann-Whitney U tests was used to compare the deviation from expected flow velocity between normal and complicated pregnancies. RESULTS: One hundred and eight pregnancies were included; 4 pregnancies were complicated with preeclampsia, 10 pregnancies with IUGR fetuses (or= 10 and >or= 11 and nasal bone multiples of the median (MoM) A, p.Ser128Tyr), located in the ECD of the FSHR. Contrary to the mutations described previously, the p.Ser128Tyr FSHR mutant displayed increase in affinity and sensitivity toward hCG and did not show any constitutive activity, nor promiscuous activation by TSH. Thus, sOHSS can be achieved from different molecular mechanisms involving each functional domains of the FSHR. Based on the structure of the FSHR/FSH complex and site-directed mutagenesis studies, we provide robust molecular models for the GPH/GPHR complexes and we propose a molecular explanation to the binding characteristics of the p.Ser128Tyr mutant. PMID- 17721930 TI - Lack of supporting evidence for a genetic association of the FKBP5 polymorphism and response to antidepressant treatment. PMID- 17721931 TI - All in the family: using inherited cancer syndromes to understand de-regulated cell signaling in brain tumors. AB - The cell signaling pathways that are tightly regulated during development are often co-opted by cancer cells to allow them to escape from the constraints that normally limit cell growth and cell movement. In this regard, de-regulated signaling in cancer cells confers a number of key tumor-associated properties, including increased cell proliferation, decreased cell death, and increased cell motility. The identification of some of these critical signaling pathways in the nervous system has come from studies of inherited cancer syndromes in which affected individuals develop brain tumors. The study of brain tumors arising in patients with neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and tuberous sclerosis complex (TSC) has already uncovered several key intracellular signaling pathways important for modulating brain tumor growth. An in-depth analysis of these intracellular signaling pathways will not only lead to an improved understanding of the process of brain tumorigenesis, but may also provide important molecular targets for future therapeutic drug design. PMID- 17721933 TI - Proceedings of the symposium Human Metabolic Interactions of Environmental Chemicals in honor of Dr. Randy L. Rose. PMID- 17721932 TI - S100A6 (calcyclin) enhances the sensitivity to apoptosis via the upregulation of caspase-3 activity in Hep3B cells. AB - S100A6 (calcyclin) is a small calcium-binding protein which has been implicated in several cellular processes such as cell cycle progression, cytoskeleton rearrangement, and exocytosis. Also the upregulation of S100A6 has been reported in a variety of tumors and linked to metastasis. However, exact intracellular roles of S100A6 related with apoptosis have not been clarified yet. Here we demonstrated that the upregulation of S100A6 enhances the cell death rate compared to the control under the apoptotic conditions. In exogenously S100A6 induced Hep3B cells, cell viability was significantly decreased compared with mock and S100A6-knockdown cells under calcium ionophore A23187 treatment. The exogenously introduced S100A6 significantly affected the caspase-3-like activity in programmed cell death through the enhanced caspase-3 expression, which was verified by promoter assay in wild or mutant S100A6-transfected Hep3B cells. Next, the promoter activity of caspase-3 was increased by 2.5-folds in wild-type S100A6-transfected cells compared to mutant 2 (E67K, mutant of EF-hand motif) or control. Our results suggest that S100A6 might be involved in the processing of apoptosis by modulating the transcriptional regulation of caspase-3. PMID- 17721934 TI - Functional activity of the mouse flavin-containing monooxygenase forms 1, 3, and 5. AB - Three functional mouse flavin-containing monooxygenases (mFMOs) (i.e., mFMO1, mFMO3, and mFMO5) have been reported to be the major FMOs present in mouse liver. To examine the biochemical features of these enzymes, recombinant enzymes were expressed as maltose-binding protein fusion proteins (i.e., MBP-mFMO1, MBP-mFMO3, and MBP-mFMO5) in Escherichia coli and isolated and purified with affinity chromatography. The substrate specificity of these three mouse hepatic FMO enzymes were examined using a variety of substrates, including mercaptoimidazole, trimethylamine, S-methyl esonarimod, and an analog thereof, and a series of 10 (N,N-dimethylaminoalkyl)-2-(trifluoromethyl)phenothiazine analogs. The kinetic parameters of the three mouse FMOs for these substrates were compared in an attempt to explore substrate structure--function relationships specific for each mFMO. Utilizing a common phenothiazine substrate for all three enzymes, we compared the pH dependence for the recombinant enzymes under similar conditions. In addition, thermal stability for mFMO1, mFMO3, and mFMO5 enzymes was examined in the presence and absence of NADPH. The results revealed unique features for mFMO5, suggesting possible impact on the functional significance of this abundantly expressed FMO5 isoform in both human and mouse liver. PMID- 17721935 TI - Genes of the antioxidant response undergo upregulation in a rodent model of nonalcoholic steatohepatitis. AB - Nonalcoholic fatty liver disease encompasses a spectrum of hepatic pathologies ranging from simple fatty liver to an inflammatory state known as nonalcoholic steatohepatitis (NASH). NASH is also characterized by severe hepatic oxidative stress. The goal of this study was to determine whether genes of the antioxidant response are induced in rodent models of nonalcoholic fatty liver disease. To simulate simple fatty liver and NASH, respectively, male Sprague-Dawley rats were fed a high-fat (HF) or a methionine and choline-deficient (MCD) diet for 8 weeks. Key marker genes of the antioxidant response that are known to undergo upregulation via activation of Nuclear Factor Erythroid 2-Related Factor 2 were measured using the branched DNA signal amplification assay. Messenger RNA levels of the antioxidant response, including NAD(P)H:quinone oxidoreductase-1 (Nqo1), Glutamate cysteine ligase catalytic (Gclc), and Heme oxygenase-1 (Ho-1), were significantly induced in MCD rat liver but not in HF rat liver. Furthermore, Nqo1 protein expression and activity underwent significant upregulation in MCD rat liver but not in HF rat liver. These data strongly indicate that the pathology induced by the MCD dietary model of NASH results in upregulation of the antioxidant response in rats. PMID- 17721936 TI - Sucrose acetate isobutyrate as an in situ forming system for sustained risperidone release. AB - The objective of this study was to develop sustained-release sucrose acetate isobutyrate (SAIB) in situ formulations of risperidone for parenteral delivery. The formulations contained SAIB, solvent (anhydrous ethanol, ethyl lactate, or N methyl-2-pyrrolidone), and additives such as polylactic acid (PLA). In vitro release profiles of risperidone from the SAIB formulations, which followed the Higuchii square root law, were obtained. An increase in SAIB content from 75% to 85% resulted in a reduction in the initial burst and the rate of risperidone release. The initial drug release could be increased by reducing the pH of the release medium and the release rate could be increased by an increase in drug loading. The burst release fell significantly from 20.0% to 3.5% following the inclusion of 10% (w/w) PLA in the formulations. In the case of this high viscosity depot system containing SAIB, anhydrous ethanol, PLA, and 25 mg/g risperidone, the in vivo biocompatible test results obtained support the use of SAIB as an injectable risperidone sustained-release formulation. PMID- 17721937 TI - Porcine vagina ex vivo as a model for studying permeability and pathogenesis in mucosa. AB - The vaginal mucosa is commonly exposed to a variety of topical agents, including chemical contraceptives, drugs for the treatment of specific pathological conditions, and pathogenic microorganisms. In vitro models can provide important information regarding the penetration and efficacy of topical compounds as well as the pathogenesis of various diseases such a menstrual toxic shock syndrome. Realistic and reproducible test systems are important if new agents are to fulfill their therapeutic potential in human populations. The selection of appropriate animal species and tissue and the use of valid in vitro systems can avoid many of the shortcomings of current animal and cell culture test systems. This review provides information about the factors that should be considered when selecting the best model to study the permeability of the human vagina. The characteristics of an ex vivo porcine model are explored and the validity of this model is demonstrated in terms of its histology, ultrastructure and composition and organization of the permeability barrier; data indicate excellent correlation of permeability and tissue response between human and porcine vaginal tissue. PMID- 17721938 TI - Contribution of variable domains to the stability of humanized IgG1 monoclonal antibodies. AB - Temperature-induced unfolding of three humanized IgG1 monoclonal antibodies and their Fab and Fc fragments was monitored by differential scanning calorimetry at neutral pH. With some exceptions, the thermogram of the intact antibody presents two peaks and the transition with the larger experimental enthalpy contains the contribution from the Fab fragments. Although the measured enthalpy was similar for all three Fab fragments studied, the apparent melting temperatures were found to vary significantly, even for Fab fragments originating from the same human germline. Therefore, we propose to use the measured enthalpy of unfolding as the key parameter to recognize the unfolding events in the melting profile of an intact IgG1 antibody. If the variable domain sequences, resulting from complementarity determining regions (CDRs) grafting and humanization, destabilize the Fab fragment with respect to the CH3 domain, the first transition represents the unfolding of the Fab fragment and the CH2 domain, while the second transition represents CH3 domain unfolding. Otherwise, the first transition represents CH2 domain unfolding, and the second transition represents the unfolding of the Fab fragment and the CH3 domain. In some cases, the DSC profile may present three transitions, with the Fab unfolding occurring at distinct temperatures compared to the melting of the CH2 and CH3 domains. If the DSC profile of a humanized IgG1 monoclonal antibody cannot be described by the model above, the result may be an indication of significant structural heterogeneity and/or of disruption of the Fab cooperative unfolding. Low stability or heterogeneity of the Fab fragment may prove problematic for long-term storage or consistency of production. Therefore, understanding the features of a DSC profile is important for clone selection and process maturation in the early stages of development of therapeutic monoclonal antibodies. PMID- 17721939 TI - Percolative drug diffusion from cylindrical matrix systems with unsealed boundaries. AB - Release of NaCl in both the axial and radial directions from cylindrical ethyl cellulose tablets were investigated by the alternating ionic current method. The pore structure of the investigated binary mixtures was examined by mercury porosimetry and scanning electron microscopy, and the nm range fractal surface dimension of tablet pore walls was extracted from krypton gas adsorption isotherms. The drug release was shown to consist of two overlapping processes of which the first was ascribed to dissolution of NaCl close to the tablet boundary followed by subsequent diffusion through a thin ethyl cellulose layer and a second from which a porosity percolation threshold of 0.22 could be extracted. As well, a cross-over to effective-medium behaviour at a porosity of approximately 0.44 was observed. The presented findings showed that drug release from matrix tablets with unsealed tablet walls substantially differs from earlier investigated release processes for which the drug has only been allowed to escape through one of the flat tablet surfaces. Thus, the present study brings forward knowledge important for the tailoring of controlled drug delivery vehicles with optimum release patterns. PMID- 17721940 TI - Significant aortic regurgitation associated with transcatheter closure of perimembranous ventricular septal defects with a deficient aortic rim. AB - We report on two patients who developed significant aortic regurgitation during transcatheter closure of a perimembranous ventricular septal defect, both requiring further surgical intervention. Both patients were noted prior to the procedure to have limited subaortic margins to the defect. The potential mechanisms for development of aortic regurgitation in this setting are discussed. PMID- 17721941 TI - Crystal structure of minoxidil at low temperature and polymorph prediction. AB - An experimental and theoretical investigation on crystal forms of the popular and ubiquitous pharmaceutical Minoxidil is presented here. A new crystallization method is presented for Minoxidil (6-(1-piperidinyl)-2,4-pyrimidinediamide 3 oxide) in ethanol-poly(ethylene glycol), yielding crystals with good quality. The crystal structure is determined at low temperature, with a final R value of 0.035, corresponding to space group P2(1) (monoclinic) with cell dimensions a = 9.357(1) A, b = 8.231(1) A, c = 12.931(2) A, and beta = 90.353(4) degrees . Theoretical calculations of the molecular structure of Minoxidil are set forward using empirical force fields and quantum-mechanical methods. A theoretical prediction for Minoxidil crystal structure shows many possible polymorphs. The predicted crystal structures are compared with X-ray experimental data obtained in our laboratory, and the experimental crystal form is found to be one of the lowest energy polymorphs. PMID- 17721942 TI - Polymer-surfactant nanoparticles for sustained release of water-soluble drugs. AB - Poor drug encapsulation efficiency and rapid release of the encapsulated drug limit the use of nanoparticles in biomedical applications involving water-soluble drugs. We have developed a novel polymer-surfactant nanoparticle formulation, using the anionic surfactant Aerosol OT (AOT) and polysaccharide polymer alginate, for sustained release of water-soluble drugs. Particle size of nanoparticles, as determined by atomic force microscopy and transmission electron microscopy, was in the range of 40-70 nm. Weakly basic molecules like methylene blue, doxorubicin, rhodamine, verapamil, and clonidine could be encapsulated efficiently in AOT-alginate nanoparticles. In vitro release studies with basic drug molecules indicate that nanoparticles released 60-70% of the encapsulated drug over 4 weeks, with near zero-order release during the first 15 days. Studies with anionic drug molecules demonstrate poorer drug encapsulation efficiency and more rapid drug release than those observed with basic drugs. Further studies investigating the effect of sodium concentration in the release medium and the charge of the drug suggest that calcium-sodium exchange between nanoparticle matrix and release medium and electrostatic interaction between drug and nanoparticle matrix are important determinants of drug release. In conclusion, we have formulated a novel surfactant-polymer drug delivery carrier demonstrating sustained release of water-soluble drugs. PMID- 17721943 TI - Physicochemical characterization and release mechanism of a novel prednisone biodegradable microsphere formulation. AB - The aim of this work was the characterization of a new formulation of prednisone long-term controlled release biodegradable microspheres. Poly(DL-lactide-co glycolide) (PLGA) polymers were used for MS preparation. A S/O/W solvent evaporation method was employed for prednisone entrapment. The system was characterized by using UV spectrophotometry, particle sizing, scanning electron microscopy, differential scanning calorimetry, X rays diffractometry, and microRaman spectroscopy. The release mechanism was studied by fitting Weibull, Peppas, Higuchi, and zero order kinetic models. The microspheres (MS) showed a good encapsulation efficiency and morphology, a suitable size and long-term release profile. Burst release was seen to depend on crystalline prednisone distributing close to the MS surface, and no particular prednisone-polymer interaction occurred. Weibull and Peppas were the best fitting models. Prednisone was released from PLGA MS following a Fickian diffusion and case II transport for higher molecular weight (MW) polymers, and a more complex mechanism involving solubilization, diffusion, and erosion, for low MW PLGA. Fully characterized PLGA MS may represent a good tool for a long-term delivery of prednisone in low-dose regimen treatments. PMID- 17721944 TI - In vivo comparative study of lipid/DNA complexes with different in vitro serum stability: effects on biodistribution and tumor accumulation. AB - To evaluate the in vivo biodistribution and expression of DOTAP-Chol/DNA complexes (lipoplexes) with different in vitro serum stability, quantitative real time PCR, in vitro luciferase expression and whole body luminescence imaging were used. In general, less tissue biodistribution, lower luciferase expression and whole body luminescence were observed for DOTAP:Chol (mol/mol 1:4)/DNA lipoplexes which had higher in vitro serum stability as compared to DOTAP:Chol (mol/mol 1:1)/DNA lipoplexes. Plasmid DNA biodistribution and expression were mainly confined to the lungs, and the results suggest that in vitro serum stability may serve as a predictor of transfection in the lung. No correlation between plasmid DNA tissue biodistribution and gene expression was observed by simultaneous determination of the level of plasmid DNA tissue biodistribution and gene expression. While high doses of the formulation possessing increased in vitro serum stability did exhibit reduced entrapment in the lung, no corresponding increase in the plasmid levels of other tissues was observed. However, this formulation did show increased accumulation in tumors that was not further enhanced by PEGylation. PMID- 17721945 TI - Oral delivery of antisense oligonucleotides in man. AB - Treatment of systemic disease with phosphorothioate antisense oligonucleotides (PS ASOs) has been accomplished using local or parenteral routes of administration to date. This report describes, for the first time, the effective oral delivery of a second generation oligonucleotide where significant milligram amounts of intact drug are absorbed in human subjects. In this study, a variety of oral solid dosage formulations were evaluated and it was determined that pulsing the delivery of sodium caprate (C10), a well-known permeation enhancer, in a novel manner may provide optimal ASO plasma bioavailability. Further, these dosage forms, containing C10 and ASO, were well tolerated in both fasted and fed volunteers. Oral absorption of the 2'-O-(2-methoxyethyl) modified antisense oligonucleotide (2'-MOE ASO), ISIS 104838, was demonstrated in healthy volunteers with an average 9.5% plasma bioavailability across four formulations tested. The greatest average performance achieved in this study for a single formulation was 12.0% bioavailability within an individual dose and subject range of 1.96-27.5%. The totality of the data suggests that formulations can be devised that allow oral administration of oligonucleotides that maintain systemic concentrations associated with inhibition of targeted human mRNA. PMID- 17721946 TI - Treatment of instent restenosis following stent-supported renal artery angioplasty. AB - OBJECTIVES: We prospectively studied the long-term outcome of endovascular treatment of instent renal artery stenosis (IRAS). BACKGROUND: Restenosis is a considerable drawback of stent-supported angioplasty of renal artery stenosis especially in small vessel diameters. The appropriate treatment strategy is not yet defined. PATIENTS AND METHODS: During a 10-year period 56 consecutive patients (65 lesions) with their first IRAS were included in a prospective follow up program (mean follow-up 53 +/- 25 months, range 6-102). Primary endpoint of the study was the reoccurence of IRAS (>or= 70%) after primarily successful treatment of the first IRAS determined by duplex ultrasound. RESULTS: Primary success rate was 100%, no major complication occurred. Nineteen lesions were treated with plain balloon angioplasty (group 1, 30%), 42 lesions with stent-in stent placement (group 2, 65%) using various bare metal balloon expandable stents, and 4 lesions with drug-eluting stent angioplasty (group 3, 6%). During follow-up, overall 21 lesions (32%) developed reoccurence of IRAS: n = 7/19 in group 1 (37%), n = 14/42 in group 2 (33%), and n = 0/4 in group 3 (0%; P = 0.573). Reoccurence of IRAS was more likely to occur in smaller vessel diameters than in larger ones [3-4mm: 4/7 (57%); 5 mm: 11/26 (42%); 6 mm: 5/25 (20%); 7 mm: 1/7 (14%), P = 0.088]. Multivariable analysis found bilateral IRAS and IRAS of both renal arteries of the same side in case of multiple ipsilateral renal arteries as independent predictors for reoccurence of IRAS. CONCLUSION: Treatment of IRAS is feasible and safe. The data demonstrate a nonsignificant trend towards lower restenosis with restenting of IRAS versus balloon angioplasty of IRAS. Individual factors influence the likelihood of reoccurence of IRAS. PMID- 17721947 TI - Vaccine production: potential engineering approaches to pandemic influenza. PMID- 17721948 TI - Equilibrium water content in native vernix and its cellular component. AB - Vernix caseosa is a naturally occurring substance coating the skin of newborn humans. Structurally, vernix contains fetal corneocytes embedded in a hydrophobic lipid matrix. Despite a relatively high water content approximating 80.7%, vernix exhibits slow water release. In this study, we quantified and contrasted the water release and uptake properties of native vernix and its isolated cellular component over the full range of water activity. Theoretical water sorption models (D'Arcy-Watt, and Frenkel-Halsey-Hill (FHH), and Guggenheim-Anderson-de Boer (GAB)) were fit to the vernix water sorption data. Each of the theoretical models provided a satisfactory description of the equilibrium water content of vernix over the water activity range 0.15-1.0. Vernix corneocytes without the surrounding lipid matrix exhibited markedly increased equilibrium water binding at water activities greater than 0.62 compared to native vernix. Resorption experiments showed full recovery of water content in both native vernix and isolated corneocytes supporting a structured internal domain. These results provide the first quantitative characterization of the water handling properties of native vernix and its cellular component. Such information may prove useful in the design of alternative skin care moisturizing formulations. PMID- 17721949 TI - Dendrimers as drug carriers: applications in different routes of drug administration. AB - Dendrimers have successfully proved themselves as useful additives in different routes of drug administration because they can render drugs greater water solubility, bioavailability, and biocompatibility. This review demonstrated the potential of dendrimers to be applied in these detailed routes with particular reference to intravenous, oral, transdermal, and ocular delivery systems. As a necessary introduction, the structures, synthesis, and properties of dendrimers were presented. Furthermore, the interaction mechanisms between dendrimers and drug molecules, including simple encapsulation, electrostatic interaction, and covalent conjugation, were elaborated. PMID- 17721951 TI - An epidemiologic approach to the development of early trauma focused intervention. AB - Early, trauma-focused intervention development has emphasized unidirectional trajectories that begin with basic research and efficacy trials followed later by effectiveness and dissemination studies. In this article, the authors present methods derived from social and clinical epidemiology that constitute foundational research in the development of early trauma-focused intervention. They also describe how population-based practice research may serve to feed back and inform what has been conceptualized as earlier stages of intervention development such as efficacy trials. Examples of relevant epidemiologic research methods are presented to illustrate these points. The authors posit that the continued application of population-based methods may produce treatments that can be feasibly applied to the unique patient, provider, organizational, and community contexts relevant to early interventions for survivors of trauma. PMID- 17721952 TI - Continuing controversy over the psychological risks of Vietnam for U.S. veterans. AB - In 1988, the National Vietnam Veterans Readjustment Study (NVVRS) reported 30.9% lifetime and 15.2% current rates of posttraumatic stress disorder (PTSD), and a strong dose/response relationship with retrospective reports of combat exposure. Skeptics argued that recall bias and other flaws inflated the results. Using a new record-based exposure measure and diagnoses in an NVVRS subsample, the authors addressed this controversy in a recent issue of Science (B. P. Dohrenwend et al., 2006). They found little evidence of falsification, an even stronger dose/response relationship and, when fully adjusted for impairment and evidence of exposure, 18.7% onset and 9.1% current rates of war-related PTSD. The fact that these rates are lower than the original NVVRS rates has stimulated continuing controversy that has tended to obscure the more important implications of the study's results. PMID- 17721953 TI - PTSD symptoms, life events, and unit cohesion in U.S. soldiers: baseline findings from the neurocognition deployment health study. AB - Relationships among a modifiable situational factor (unit cohesion), prior stressful life events, and posttraumatic stress disorder (PTSD) symptoms were assessed in 1,579 U.S. Army soldiers with no history of contemporary war zone deployment. It was predicted that unit cohesion would attenuate the dose-response relationship between past stressor exposures and PTSD symptoms at relatively moderate levels of exposure. Consistent with this hypothesis, regression analysis revealed that life experiences and unit cohesion strongly and independently predicted PTSD symptoms, and that unit cohesion attenuated the impact of life experiences on PTSD. Some military personnel reported significant predeployment, stress-related symptoms. These symptoms may serve as vulnerabilities that could potentially be activated by subsequent war-zone deployment. Higher predeployment unit cohesion levels appear to ameliorate such symptoms, potentially lessening future vulnerability. PMID- 17721954 TI - Personality characteristics of adult survivors of childhood trauma. AB - Lenore Terr (1991) proposed a framework for childhood trauma that distinguishes between single-incident trauma (Type I) and repeated or prolonged trauma (Type II). Terr's framework and data collected from the National Comorbidity Survey (NCS) are used to examine differences in personality between adult survivors of childhood Type I trauma, childhood Type II trauma, and a control group of adults not traumatized as children. Groups were compared on five personality scales. Results indicate that individuals in the trauma categories scored higher in neuroticism and openness to new experiences than individuals in the control group. The Type I group was lower than the control group on interpersonal dependency, whereas the Type II group scored higher than the control group on this measure. PMID- 17721955 TI - A 1.5-year follow-up of an Internet-based intervention for complicated grief. AB - Only recently have psychotherapeutic interventions for complicated grief been developed and evaluated in randomized controlled trials. These trials have reported significant reductions in complicated grief and related symptoms in response to treatment relative to control groups. However, little is known about the long-term outcomes of these treatments. The authors present an evaluation of a 1.5-year follow-up of an Internet-based cognitive-behavioral intervention for complicated grief. Treatment group patients (n = 22) were administered various assessments of complicated grief indicators, including the Impact of Event Scale, the anxiety and depression subscales of the Brief Symptom Inventory, and the SF 12. Results indicate that the reduction in symptoms of complicated grief observed at posttreatment was maintained at 1.5-year follow-up. PMID- 17721956 TI - Circumstances of service and gender differences in war-related PTSD: findings from the National Vietnam Veteran Readjustment Study. AB - Data from the National Vietnam Veteran Readjustment Study (NVVRS) revealed a prevalence of current posttraumatic stress disorder (PTSD) in female Vietnam Theater veterans half the size of the prevalence in their male counterparts. This stands in contrast to the elevated prevalence of PTSD in women obtained in general population surveys. This study undertakes further analyses of gender differences in the NVVRS and how these differences might be specified by the amount and type of exposure to war-zone stress. The findings indicate that male elevations in PTSD are limited to men who served under circumstances of high probable severity of war-zone stress exposure. When prewar demographic differences are controlled, male veterans in low-exposure circumstances display a level of PTSD prevalence substantially lower than female veterans. PMID- 17721957 TI - Differentiating biological correlates of risk, PTSD, and resilience following trauma exposure. AB - Risk and resilience factors presumably explain the individual differences in the response to adversity. However, little is known about how such factors are related. Risk and protective factors may reflect a quantitative difference along a single dimension (e.g., low IQ might be associated with risk and high IQ with resilience); however, they may also refer to orthogonal constructs that interact and/or moderate stress effects to increase or diminish the probability of developing trauma-related psychopathology (e.g., good coping could offset low IQ). The authors illustrate experimental strategies for distinguishing between these possibilities for any putative measure relating to symptom development, using a database that includes published and unpublished psychological and biological variables from a relatively homogenous cohort of exposed and nonexposed veterans. PMID- 17721958 TI - Revisiting Dohrenwend et al.'s revisit of the National Vietnam Veterans Readjustment Study. AB - Critics of the National Vietnam Veterans Readjustment Study (NVVRS) suspect that the NVVRS overestimated the prevalence of posttraumatic stress disorder (PTSD) among Vietnam veterans. Dohrenwend et al. (2006) confirmed this suspicion. Dohrenwend et al.'s reanalysis of the NVVRS data resulted in a prevalence estimate 40% lower than the original NVVRS estimate. Furthermore, had they required clinically significant functional impairment, the prevalence rate would have been 65% lower than the original NVVRS rate. That is, the current (late 1980s) prevalence estimates for PTSD are 15.2% (original NVVRS), 9.1% (Dohrenwend et al.), and 5.4% (clinically significant functional impairment). The policy implications of these findings are discussed. PMID- 17721959 TI - Validation of a screening instrument for posttraumatic stress disorder in a community sample of Bedouin men serving in the Israeli Defense Forces. AB - This study evaluates the performance of the Screen for Posttraumatic Stress Disorder (SPTSS) in the assessment of a high-risk ethnic minority sample. Participants included 317 Bedouin men serving in the Israeli Defense Forces (IDF), who disclosed extensive trauma and loss. The sensitivity and specificity of the SPTSS were calculated using the Structured Clinical Interview for DSM-IV (SCID) as the criterion for posttraumatic stress disorder (PTSD), which was diagnosed in 14.5% of respondents. Receiver operating characteristic (ROC) analysis using the SPTSS total mean scores maximized classification accuracy at a cut point of 5.5, yielding equal sensitivity and specificity rates of 89%. Likelihood ratios indicated that men with positive screens who did not meet criteria for PTSD were likely to report significant emotional distress and functional impairment. PMID- 17721960 TI - Dissociation and pain perception: an experimental investigation. AB - Dissociative symptoms and abnormalities in pain perception have been associated with a range of disorders. The authors tested whether experimentally induced increases in state dissociation would cause an analgesic response. Participants (N = 120) were randomized to a dissociation induction condition via audiophotic stimulation or a credible control condition and were compared on pre- and postchanges in subjective pain and immersion time in response to a standard cold pressor test. Unexpectedly, the dissociation induction led to small, but significant increases in subjective pain and did not lead to greater immersion time. An exploratory analysis revealed that increases in absorption and derealization significantly predicted increased subjective pain and increased immersion time, respectively. PMID- 17721961 TI - Applications of dialectical behavior therapy to the treatment of complex trauma related problems: when one case formulation does not fit all. AB - In this article, the authors take the perspective that effective treatment of complex trauma-related problems requires, in the absence of empirically supported treatments, a reliance on theory, idiographic assessment, and empirically supported principles of change. Dialectical behavior therapy (DBT; M. M. Linehan, 1993) is used to demonstrate the applicability of this approach to the treatment of multiproblem, heterogeneous populations in general. Two case studies are presented that highlight the utility of DBT principles to complex trauma-related problems specifically. PMID- 17721962 TI - School-based intervention for prevention and treatment of elementary-students' terror-related distress in Israel: a quasi-randomized controlled trial. AB - A school-based intervention for preventing and reducing children's posttraumatic stress-related symptoms, somatic complaints, functional impairment, and anxiety due to exposure to terrorism was evaluated. In a quasi-randomized controlled trial, elementary school students were randomly assigned to an eight-session structured program, "Overshadowing the Threat of Terrorism" or to a waiting list control comparison group. Two months postintervention, the study group reported significant improvement on all measures. The authors conclude that a school-based universal intervention may significantly reduce posttraumatic stress disorder- (PTSD-) related symptoms in children repeatedly exposed to terrorist attacks and propose that it serve as a component of a public mental health approach dealing with children exposed to ongoing terrorism in a country ravaged by war and terrorism. PMID- 17721963 TI - Posttraumatic stress symptom severity predicts marijuana use coping motives among traumatic event-exposed marijuana users. AB - The present study examines the relation between posttraumatic stress symptom severity and motives for marijuana use among 103 (55 women) young adult marijuana users (current) who reported experiencing at least one traumatic event in their lifetime. As expected, after covarying for the theoretically relevant variables of frequency of past 30-day marijuana use, number of cigarettes smoked per day, and volume of alcohol consumed, posttraumatic stress symptom severity was significantly related to marijuana use coping motives, but no other motives for marijuana use. Results are discussed in relation to better understanding the role of coping-motivated marijuana use among young adults experiencing posttraumatic stress. PMID- 17721964 TI - Self-selection bias in sleep and psychophysiological studies of posttraumatic stress disorder. AB - Psychobiological studies of posttraumatic stress disorder (PTSD) often challenge participants to assess the dynamics of systems evolved to organize responses to extreme events. Informed consent insures that volunteers have every opportunity to preevaluate the conditions of the research experience and decline if made uncomfortable by them. Notwithstanding their necessity, these protections set the stage for self-selection phenomena that may bias study outcomes. This study compared prospectively obtained psychometric data from 196 participants and 1229 nonparticipants in sleep and psychophysiological studies of PTSD. Lower subjective nightmare severity was endorsed by persons who later agreed to participate in a study of baseline sleep, an observation consistent with the low nightmare frequencies observed in most laboratories studies of sleep in PTSD. PMID- 17721965 TI - Confounding the critics: the Dohrenwend and colleagues reexamination of the National Vietnam Veteran Readjustment Study. AB - The National Vietnam Veteran Readjustment Study (NVVRS; R. A. Kulka et al., 1988) has been highly influential, but critics argue that the study had several flaws. In this article, the author addresses how the recent NVVRS reevaluation (B. P. Dohrenwend et al., 2006) refutes most of the critic's major concerns including that self-report of exposure to war-zone stressors could not be verified, that PTSD did not require functional impairment, and that PTSD prevalence was too high for a low-intensity war in which relatively few veterans were assigned to combat military operation specialties. The author also addresses misleading statements made by critics discussing the NVVRS, the reevaluation, and related articles. The proper role of science and public policy, the importance of reporting findings accurately, and placing findings in proper perspective are discussed. PMID- 17721966 TI - Stigma and the military: evaluation of a PTSD psychoeducational program. AB - Trauma risk management (TRiM) is an intensive posttraumatic stress disorder (PTSD) psychoeducational management strategy based on peer-group risk assessment developed by the UK Royal Navy (RN). TRiM seeks to modify attitudes about PTSD, stress, and help-seeking and trains military personnel to identify at-risk individuals and refer them for early intervention. This quasiexperimental study found that TRiM training significantly improved attitudes about PTSD, stress, and help-seeking from TRiM-trained personnel. There was a nonsignificant effect on attitudes to seeking help from normal military support networks and on general health. Within both the military and civilian populations, stigma is a serious issue preventing help-seeking and reducing quality of life. The results suggest that TRiM is a promising antistigma program within organizational settings. PMID- 17721967 TI - Traumatic events and posttraumatic stress in cross-cultural mission assignments. AB - In addition to cross-cultural and environmental stressors, aid workers and missionaries are frequently exposed to trauma. We explored the frequency of traumatic events, their mental health impact, and factors associated with posttraumatic stress in two groups of missionaries, one representing a predominantly stable setting (Europe) and the other an unstable setting (West Africa). The 256 participants completed self-report measures assessing lifetime traumatic events, current posttraumatic stress, depressive and anxiety symptoms, resilience, and functioning. The rate of traumatic events was significantly higher in the unstable setting. More-frequent traumatic events were associated with higher posttraumatic stress. Factors associated with the severity of posttraumatic stress were depression, functional impairment, subjective severity and number of traumatic events, and the level of resilience. PMID- 17721968 TI - Impact of behavioral contingency management intervention on coping behaviors and PTSD symptom reduction in cocaine-addicted homeless. AB - The purpose of this study was to examine changes in posttrauma symptoms among 118 homeless cocaine-dependent adults participating in a randomly controlled trial studying effective treatments for dually diagnosed homeless individuals. Among those with trauma exposure and PTSD symptoms, the group receiving more behaviorally intensive, contingency management treatment had significantly greater reductions in PTSD symptomatology than did the group receiving less intensive treatment. Regression analyses revealed that greater positive distraction coping and lower negative avoidance coping at baseline, in addition to changes in avoidance coping over the 6-month study period, were significantly related to greater symptom and severity reductions. The study provides some initial evidence of important treatment outcomes other than abstinence in addiction-related interventions. PMID- 17721970 TI - The psychological risks of Vietnam: the NVVRS perspective. AB - In recent years, controversy concerning the psychological consequences of service in the Vietnam war has rearisen. In this article, the Co-Principal Investigators of the National Vietnam Veterans Readjustment Study (NVVRS) provide a perspective on new findings reported by B. P. Dohrenwend et al. (2006) that addresses criticisms of the NVVRS PTSD (posttraumatic stress disorder) prevalence findings, and on a perspective that was provided by R. J. McNally (2006) in an accompanying commentary. They find that Dohrenwend et al.'s study, which evaluated empirically a variety of the critics' alternative explanations and found little support for any of them, represents a landmark contribution to the trauma field. However, they found that McNally's commentary misrepresented the history and context of the NVVRS, and then misinterpreted Dohrenwend et al.'s findings and their importance. PMID- 17721971 TI - Individual differences in fear: isolating fear reactivity and fear recovery phenotypes. AB - Although different people respond differently to threatening events, animal research on the neural basis of fear tends to focus on typical responses. Yet there are substantial individual differences between animals exposed to identical behavioral procedures. In an effort to begin to understand the nature and causes of fear variability and resilience, we separated outbred Sprague-Dawley rats into high and low reactivity, and fast and slow recovery phenotypes, based on freezing levels during fear conditioning and extinction, respectively. Subsequent tests revealed stable differences in both measures, indicating that fear responses reflect trait-like phenotypes in outbred animals. Because clinical disorders may reflect extreme phenotypes, identification of the biological basis for these differences could provide insights into human individual differences in fear. PMID- 17721969 TI - Partial and full PTSD in Brazilian ambulance workers: prevalence and impact on health and on quality of life. AB - A cross-sectional survey for posttraumatic stress disorder (PTSD) was conducted with 234 Brazilian ambulance workers (180 men and 54 women) using a sociodemographic questionnaire, the Posttraumatic Stress Disorder Checklist Civilian Version, and the Short Form Health Survey-36. Current prevalence rates for full and partial PTSD were 5.6% (men = 6.7%, women = 1.9%) and 15% (men = 13.3%, women = 20.4%), respectively. Male workers with full PTSD were more likely to be nonmarried (75% vs. 43%) and those with partial PTSD reported more emotional problems (65.2% vs. 30%) and medical visits (67% vs. 44%) than the controls. Workers with PTSD showed impairment in the physical and mental domains of the SF-36, whereas workers with partial PTSD had only the later compromised. The characteristics and the level of exposure to trauma of the study population may account for the low prevalence of PTSD. PMID- 17721972 TI - Stress inoculation-induced indications of resilience in monkeys. AB - The negative consequences of stress are well-recognized in mental health research. Exposure to early life stressors, for example, increases the risk for the development of mood, anger, anxiety, and substance abuse disorders. Interestingly, however, early life stressors have also been linked to the subsequent development of resilience. Variously described as inoculating, immunizing, steeling, toughening, or thriving, the hypothesis that early life stressors provide a challenge that, when overcome, induces adaptations that enhance emotional processing, cognitive control, curiosity, and neuroendocrine regulation is examined in this review of squirrel monkey research. PMID- 17721973 TI - Predictors of posttraumatic stress symptoms among runaway youth utilizing two service sectors. AB - Youth who run away often experience situations that produce symptoms of traumatic distress. This exploratory study assessed predictors of trauma symptomatology among runaway youth who had been admitted to youth emergency shelter services or juvenile detention. Findings demonstrated high levels of trauma-related symptoms for both groups. Worry about family, greater runaway episodes, and living with a father who abused alcohol/drugs significantly predicted higher posttraumatic stress symptoms in detained youth, whereas only worry about family relationships predicted higher trauma symptom scores among youth in emergency shelter care. Findings suggest distressful family life may induce complex emotional responses in youth. Although services to runaway youth must continue to focus on safe, short-term residential care, trauma issues must be acknowledged. PMID- 17721974 TI - Adult sexual abuse is associated with elevated neurohormone levels among women with PTSD due to childhood sexual abuse. AB - Posttraumatic stress disorder (PTSD) has been associated with reduced, similar, or increased urinary cortisol levels. The authors identified a factor that might contribute to such variability when they obtained 24-hour urinary neurohormone profiles on 69 women with PTSD due to childhood sexual abuse. Half (n = 35) had subsequently experienced adult sexual abuse (ASA) while the other half (n = 34) had not. The ASA group had significantly elevated urinary cortisol, norepinephrine and dopamine levels in comparison to the non-ASA group. Neither a history of childhood or adult physical abuse nor other variables contributed to this finding. The results suggest that the psychobiological consequences of exposure to the same traumatic event may differ as a result of an interaction between age and the composite history of trauma exposure. PMID- 17721975 TI - Feasibility and effectiveness of cognitive-behavioral therapy for posttraumatic stress disorder in preschool children: two case reports. AB - New evidence raises concerns that posttraumatic stress disorder (PTSD) in preschool children is unremitting over years even with unstructured community treatment. This report presents proof of concept of the feasibility and effectiveness of a structured therapy, cognitive-behavioral therapy (CBT), for preschool PTSD that follows a range of different traumatic events. Two cases are presented, including transcribed dialogue, from a motor vehicle accident and Hurricane Katrina, respectively. Three key CBT feasibility questions were examined; it was concluded that (a) young children can cooperate meaningfully in structured, trauma-related exposure exercises; (b) they can utilize relaxation techniques successfully; and (c) highly anxious parents do not inhibit their children's improvement per se as long as they can facilitate the manual techniques. Clinicians need to be aware of emerging evidence-based treatment for preschool children. PMID- 17721976 TI - Protein isolated from biopharmaceutical formulations cannot be used for comparative studies: Follow-up to "a case study using Epoetin Alfa from Epogen and EPREX". AB - In the biotechnology area, the issue of comparability with an innovator product is complex. Ideally, a side-by-side comparison of physical properties would be part of the demonstration of comparability. However, biogeneric companies do not have access to the bulk drug substance from the innovator company for biophysical comparison, and isolation of protein from marketed product cannot be guaranteed to produce material that is identical to the bulk drug substance from which it was prepared. In a recently published study, protein was isolated from marketed product and comparative studies performed. In a follow-up investigation of the published work, we demonstrate here that even a simple isolation procedure can significantly compromise the protein, which raises serious questions about the interpretation of that study, and in a broader context the value of any studies done with such "out-of-process" protein. PMID- 17721977 TI - Missense and nonsense mutations in the alternatively-spliced exon 2 of COL2A1 cause the ocular variant of Stickler syndrome. AB - Stickler syndrome type I (STL1) is a phenotypically heterogeneous disorder characterized by ocular and extraocular features. It is caused by null-allele mutations in the COL2A1 gene that codes for procollagen II. COL2A1 precursor mRNA undergoes alternative splicing, resulting in two isoforms, a long form including exon 2 (type IIA isoform) and a short form excluding exon 2 (type IIB isoform). The short form is predominantly expressed by differentiated chondrocytes in adult cartilage, and the long form in chondroprogenitor cells during early development and in the vitreous of the eye, which is the only adult tissue containing procollagen IIA. Recent evidence indicates that due to the tissue-specific expression of these two isoforms, premature termination codon mutations in exon 2 cause Stickler syndrome with minimal or no extraocular manifestations. We describe here two mutations in exon 2 of COL2A1 in three patients with predominantly ocular Stickler syndrome: Cys64Stop in two patients, and a novel structural mutation, Cys57Tyr, in one patient. RT-PCR of total lymphoblast RNA from one patient with the Cys64Stop mutation revealed that only the normal allele of the IIA form was present, indicating that the mutation resulted either in complete loss of the allele by nonsense-mediated mRNA decay or by skipping of exon 2 via nonsense-mediated altered splicing, resulting in production of the type IIB isoform. The results of COL2A1 minigene expression studies suggest that both Cys64Stop and Cys57Tyr alter positive cis regulatory elements for splicing, resulting in a lower IIA:IIB ratio. PMID- 17721979 TI - Optical coherence tomography as a tool for measuring morphogenetic deformation of the looping heart. AB - Optical coherence tomography (OCT) was used to investigate morphogenesis of the embryonic chick heart during the first phase of looping (c-looping), as the heart bends and twists into a c-shaped tube. The present study focuses on the morphomechanical effects of the splanchnopleure (SPL), a membrane that has been shown to play a major role in cardiac torsion by pressing against the ventral surface of the heart. Without the SPL, rightward torsion (rotation) is delayed. The images show that compressive forces exerted by the SPL alter the shapes of the heart tube and primitive atria, as well as their spatial relationships. The SPL normally holds the heart in the plane of the embryo and forces cardiac jelly (CJ) out of adjacent regions in the atria. When the SPL is removed, cross sections become more circular, CJ is more uniformly distributed, and the heart displaces ventrally. In addition, OCT-based morphogenetic strain maps were measured during looping by tracking the three-dimensional motions of microspheres placed on the myocardium. The spatial-temporal patterns of the strains correlated well with the observed behavior of the heart, including delayed torsion that occurs in SPL-lacking embryos. These results illustrate the potential of OCT as a tool in studies of morphogenesis, as well as provide a better understanding of the mechanical forces that drive cardiac looping. PMID- 17721978 TI - Oxidant-induced atrogin-1 and transforming growth factor-beta1 precede alcohol related myopathy in rats. AB - Alcohol-related chronic myopathy is characterized by severe biochemical and structural changes to skeletal muscle. Our goals were to: (1) identify early regulatory elements that precede the overt manifestation of plantaris atrophy; and (2) circumvent these derangements by supplementing alcohol-fed rats with the glutathione precursor, procysteine. After 6 weeks of daily ingestion, before the development of overt atrophy of the plantaris muscle, alcohol increased several markers of oxidative stress and increased gene expressions of atrogin-1 and transforming growth factor-beta1 (TGF-beta1) by approximately 60- and approximately 65-fold, respectively, which were attenuated by procysteine supplementation. Interestingly, after 28 weeks of alcohol ingestion, when overt plantaris atrophy had developed, atrogin-1 and TGF-beta1 gene expression had returned to baseline levels. Together, these findings suggest that alcohol induced, redox-sensitive alterations drive pro-atrophy signaling pathways that precede muscle atrophy. Therefore, targeted anti-oxidant treatments such as procysteine supplementation may benefit individuals with chronic alcohol abuse, particularly if given prior to the development of clinically significant myopathy. PMID- 17721980 TI - Techniques for modeling muscle-induced forces in finite element models of skeletal structures. AB - This work introduces two mechanics-based approaches to modeling muscle forces exerted on curvilinear bone structures and compares the results with two traditional ad hoc methods of muscle loading. These new models use a combination of tensile, tangential, and normal traction loads to account for muscle fibers wrapped around curved bone surfaces. A computer program was written to interface with a commercial finite element analysis tool to automatically apply traction loads to surface faces of elements in muscle attachment regions according to the various muscle modeling methods. We modeled a highly complex skeletal structure, the skull of a Jamaican fruit bat (Artibeus jamaicensis), to compare the four muscle-loading methods. While reasonable qualitative agreement was found in the states of stress of the skull between the four muscle load modeling methods, there were substantial quantitative differences predicted in the stress states in some high stressed regions of the skull. Furthermore, our mechanics-based models required significantly less total applied muscle force to generate a bite-point reaction force identical to those produced by the ad hoc muscle loading models. Although the methods are not validated by in vivo data, we submit that muscle load modeling methods that account for the underlying physics of muscle wrapping on curved bone surfaces are likely to provide more realistic results than ad hoc approaches that do not. We also note that, due to the geometric complexity of many bone structures--such as the skull analyzed here--load transmission paths are difficult to conceptualize a priori. Consequently, it is difficult to predict spatially where the results of finite element analyses are likely to be compromised by using ad hoc muscle modeling methods. For these reasons, it is recommended that a mechanics-based method be adopted for determination of the proper traction loads to be applied to skeletal structures due to muscular activity. PMID- 17721981 TI - Linear and geometric morphometric analysis of long bone scaling patterns in Jurassic neosauropod dinosaurs: their functional and paleobiological implications. AB - Neosauropod dinosaurs were gigantic, herbivorous dinosaurs. Given that the limb skeleton is essentially a plastic, mobile framework that supports and moves the body, analysis of long bone scaling can reveal limb adaptations that supported neosauropod gigantism. Previously, analyses of linear dimensions have revealed a relatively isometric scaling pattern for the humerus and femur of neosauropods. Here, a combined scaling analysis of humerus and femur linear dimensions, cortical area, and shape across six neosauropod taxa is used to test the hypothesis that neosauropod long bones scaled isometrically and to investigate the paleobiological implications of these trends. A combination of linear regression and geometric morphometrics analyses of neosauropod humeri and femora were performed using traditional and thin-plate splines approaches. The neosauropod sample was very homogeneous, and linear analyses revealed that nearly all humerus and femur dimensions, including cortical area, scale with isometry against maximum length. Thin-plate splines analyses showed that little to no significant shape change occurs with increasing length or cortical area for the humerus or femur. Even with the exclusion of the long-limbed Brachiosaurus, the overall trends were consistently isometric. These results suggest that the mechanical advantage of limb-moving muscles and the relative range of limb movement decreased with increasing size. The isometric signal for neosauropod long bone dimensions and shape suggests these dinosaurs may have reached the upper limit of vertebrate long bone mechanics. Perhaps, like stilt-walkers, the absolutely long limbs of the largest neosauropods allowed for efficient locomotion at gigantic size with few ontogenetic changes. PMID- 17721983 TI - Allometries throughout the late prenatal and early postnatal human craniofacial ontogeny. AB - Craniofacial shape changes throughout the late prenatal and early postnatal ontogeny (32-47 weeks of gestational age) were explored. The purpose was to evaluate whether the skull follows an allometric growth pattern, as was observed in other ontogenetic periods, and to assess shape variation patterns for the cranial vault, cranial base, and face. Thirty three-dimensional landmarks were registered in 54 skulls. Wire-frames were built with landmarks to observe shape variation in the following cranial components: anteroneural, midneural, posteroneural, optic, respiratory, masticatory, and alveolar. The landmark configurations were subjected to generalized Procrustes analyses, and the shape coordinates obtained were subjected to Principal Components Analyses. Multivariate regression of the shape variables (the principal components) on the size vector (the centroid size) was performed to assess allometries. Transformation grids were constructed to identify how cranial components interact across ontogeny. Results indicated that highly significant shape changes depend on size changes. Important shape variation in the vault, small variation in the cranial base, and no variation in the face were observed. Brain growth is proposed to be the major influence on craniofacial shape change, which produces a relative elongation and compression of midneural and posteroneural components. The cranial base elongates by intrinsic factors and affects position of the face. Ontogenetically, the cranial base seems to be independent with respect to brain growth, in contrast to what has been suggested in comparisons at higher taxonomic levels. PMID- 17721982 TI - Treatment of severe infrapopliteal vascular disease using a novel atherectomy device: a case report. AB - We report two first in man cases of percutaneous revascularization for severe intrapopliteal arterial disease using the novel PV atherectomy device. PMID- 17721985 TI - Is PFO sizing necessary? PMID- 17721984 TI - Neuromuscular anatomy and evolution of the cetacean forelimb. AB - The forelimb of cetaceans (whales, dolphins, and porpoises) has been radically modified during the limb-to-flipper transition. Extant cetaceans have a soft tissue flipper encasing the manus and acting as a hydrofoil to generate lift. The neuromuscular anatomy that controls flipper movement, however, is poorly understood. This study documents flipper neuromuscular anatomy and tests the hypothesis that antebrachial muscle robustness is related to body size. Data were gathered during dissections of 22 flippers, representing 15 species (7 odontocetes, 15 mysticetes). Results were compared with published descriptions of both artiodactyls and secondarily aquatic vertebrates. Results indicate muscle robustness is best predicted by taxonomic distribution and is not a function of body size. All cetaceans have atrophied triceps muscles, an immobile cubital joint, and lack most connective tissue structures and manus muscles. Forelimbs retain only three muscle groups: triceps (only the scapular head is functional as the humeral heads are vestigal), and antebrachial extensors and flexors. Well developed flexor and extensor muscles were found in mysticetes and basal odontocetes (i.e., physeterids, kogiids, and ziphiids), whereas later diverging odontocetes (i.e., monodontids, phocoenids, and delphinids) lack or reduce these muscles. Balaenopterid mysticetes (e.g., fin and minke whales) may actively change flipper curvature, while basal odontocetes (e.g., sperm and beaked whales) probably stiffen the flipper through isometric contraction. Later diverging odontocetes lack musculature supporting digital movements and are unable to manipulate flipper curvature. Cetacean forelimbs are unique in that they have lost agility and several soft tissue structures, but retain sensory innervations. PMID- 17721987 TI - Interventional stroke therapy: current state of the art and needs assessment. AB - The primary therapeutic strategy for ischemic stroke, as for MI patients, is early reperfusion. Improvement in stroke treatment will require dedicated stroke centers to emulate MI quality indicators such as minimizing the "door-to-balloon time". A critical element in achieving this goal will be organizing the existing multidisciplinary pool of carotid interventionalists to provide the endovascular component of the acute care for ischemic stroke patients. PMID- 17721988 TI - Mirror neuron system: basic findings and clinical applications. AB - In primates, ventral premotor and rostral inferior parietal neurons fire during the execution of hand and mouth actions. Some cells (called mirror neurons) also fire when hand and mouth actions are just observed. Mirror neurons provide a simple neural mechanism for understanding the actions of others. In humans, posterior inferior frontal and rostral inferior parietal areas have mirror properties. These human areas are relevant to imitative learning and social behavior. Indeed, the socially isolating condition of autism is associated with a deficit in mirror neuron areas. Strategies inspired by mirror neuron research recently have been used in the treatment of autism and in motor rehabilitation after stroke. PMID- 17721989 TI - Comparison of the interferon-tau expression from primary trophectoderm outgrowths derived from IVP, NT, and parthenogenote bovine blastocysts. AB - The expression of interferon-tau (IFN-tau) is essential for bovine embryo survival in the uterus. An evaluation of IFN-tau production from somatic cell nuclear transfer (NT)-embryo-derived primary trophectoderm cultures in comparison to trophectoderm cultured from parthenogenote (P) and in vitro matured, fertilized, and cultured (IVP) bovine embryos was performed. In Experiment 1, the success/failure ratio for primary trophectoderm colony formation was similar for IVP and NT blastocysts [IVP = 155/29 (84%); NT 104/25 (81%)], but was decreased (P = .05) for P blastocysts [54/43 (56%)]. Most trophectoderm colonies reached diameters of at least 1 cm within 3-4 weeks, and at this time, 72 hr conditioned cell culture medium was measured for IFN-tau concentration by antiviral activity assay. The amount of IFN-tau produced by IVP-outgrowths [4311 IU/mL (n = 155)] was greater (P < .05) than that from NT- [626 IU/mL (n = 104)] and P - [1595 IU/mL (n = 54)] derived trophectoderm. Differential expression of IFN-tau was confirmed by immunoblotting. In Experiment 2, colony formation was again similar for IVP and NT blastocysts [IVP = 70/5 (93%); NT 67/1 (99%)] and less (P < .05) for P blastocysts [65/27 (70%)]. Analysis of trophectoderm colony size after 23 days in culture showed a similar relationship with P-derived colonies being significantly smaller in comparison to IVP and NT colonies. A differential expression of IFN-tau was also observed again, but this time as measured over time in culture. Maximal IFN-tau production was found at day-14 of primary culture and diminished to a minimum by the 23rd day. PMID- 17721990 TI - Methylglyoxal and high glucose co-treatment induces apoptosis or necrosis in human umbilical vein endothelial cells. AB - Hyperglycemia and elevation of methylglyoxal (MG) are symptoms of diabetes mellitus (DM). We previously showed that high glucose (HG; 30 mM) or MG (50-400 microM) could induce apoptosis in mammalian cells, but these doses are higher than the physiological concentrations of glucose and MG in the plasma of DM patients. The physiological concentration of MG and glucose in the normal blood circulation is about 1 microM and 5 mM, respectively. Here, we show that co treatment with concentrations of MG and glucose comparable to those seen in the blood circulation of DM patients (5 microM and 15-30 mM, respectively) could cause cell apoptosis or necrosis in human umbilical vein endothelial cells (HUVECs) in vitro. HG/MG co-treatment directly increased the reactive oxygen species (ROS) content in HUVECs, leading to increases in intracellular ATP levels, which can control cell death through apoptosis or necrosis. Co-treatment of HUVECs with 5 microM MG and 20 mM glucose significantly increased cytoplasmic free calcium levels, activation of nitric oxide synthase (NOS), caspase-3 and -9, cytochrome c release, and apoptotic cell death. In contrast, these apoptotic biochemical changes were not detected in HUVECs treated with 5 microM MG and 30 mM glucose, which appeared to undergo necrosis. Pretreatment with nitric oxide (NO) scavengers could inhibit 5 microM MG/20 mM glucose-induced cytochrome c release, decrease activation of caspase-9 and caspase-3, and increase the gene expression and protein levels of p53 and p21, which are known to be involved in apoptotic signaling. Inhibition of p53 protein expression using small interfering RNA (siRNA) blocked the activation of p21 and the cell apoptosis induced by 5 microM MG/20 mM glucose. In contrast, inhibition of p21 protein expression by siRNA prevented apoptosis in HUVECs but had no effect on p53 expression. These results collectively suggest that the treatment dosage of MG and glucose could determine the mode of cell death (apoptosis vs. necrosis) in HUVECs, and both ROS and NO played important roles in MG/HG-induced apoptosis of these cells. PMID- 17721991 TI - Combination of cytologic evaluation and quantitative digital cytometry is reliable in detecting recurrent disease in patients with urinary diversions. AB - BACKGROUND: Detecting recurrent bladder carcinoma early is important because it is a multifocal disease that may affect the bladder mucosa, ureters, urethra, and renal pelvis and is associated with high morbidity and mortality rates. However, specimens from patients who have undergone cystectomy with urinary diversion can be difficult to interpret by cytologic evaluation because they often contain degenerated epithelial cells, histiocytes, acute inflammatory cells, bacteria, and cellular debris. In this retrospective study, the reliability of quantitative digital cytometry (QDC) in conjunction with cytologic evaluation in detecting recurrent disease was determined in these patients. METHODS: In all, 116 specimens were identified from the cytology files from 83 patients who had undergone radical cystectomy with urinary diversion for bladder carcinoma at the study institution between 2002 and 2005; all specimens underwent cytologic evaluation and 105 underwent QDC. Two cytospin slides were prepared for cytologic evaluation and 1 for QDC. At least 100 of the most atypical cells were interactively digitized and evaluated for ploidy, the percentage of proliferating cells, and the percentage of cells with a DNA content greater than 5c. Based on these parameters, the DNA histograms were grouped by pattern: diploid, abnormal diploid, tetraploid, and aneuploid. The cytologic evaluation and QDC results were compared with the clinical follow-up data. RESULTS: In all, 103 specimens were negative for recurrent disease or had atypical cells on cytologic examination and were found to have diploid or abnormal diploid patterns on QDC. None of these cases had clinical evidence of upper urinary tract disease at the time the first specimen was obtained. However, recurrent urothelial carcinoma was found in subsequent conduit specimens from 2 patients. Thirteen specimens from 9 patients were suspicious or positive for malignancy by cytology. Five of these patients had an upper urinary tract recurrence and their specimens were found to be abnormal on cytologic evaluation and QDC, with 15% of cells with a DNA content greater than 5c. CONCLUSIONS: Combined cytologic evaluation and QDC is a reliable method of detecting recurrent disease in patients with urinary diversions and can be used to regularly monitor these high-risk patients. PMID- 17721992 TI - Increasing incidence and continued dismal outcome of primary central nervous system lymphoma in Norway 1989-2003 : time trends in a 15-year national survey. AB - BACKGROUND: The incidence of primary central nervous system lymphoma (PCNSL) appears to be increasing in some countries, whereas it is stable in others. Many reports the last decades have suggested that there have been improvements in the treatment of PCNSL. The objective of this study was to analyze time trends in the incidence, clinical features, histologic diagnosis, treatment, and outcome of nonacquired immunodeficiency syndrome (non-AIDS) PCNSL in Norway from 1989 to 2003. METHODS: Patients were identified by a chart review of all patients who had a recorded diagnosis of PCNSL from 1989 to 2003 in The Norwegian Cancer Registry. The histologic and cytologic material from each patient was re-examined by pathologists. Time trends were analyzed according to year of diagnosis grouped into 3 5-year periods: 1989-1993, 1994-1998, and 1999-2003. RESULTS: There were 98 patients who had confirmed, newly diagnosed non-AIDS PCNSL in Norway from 1989 to 2003. The incidence rate increased during the consecutive 5-year periods from 0.89 per million during 1989 to 1993, to 1.74 per million during 1994 to 1998, and to 1.82 per million during 1999 to 2003 (P = .013). Diagnostic delay and overall survival did not improve with time. Survival decreased from 1999 to 2003 compared with survival from 1994 to 1998, which was explained in part by reduced performance status and fewer patients receiving combined chemotherapy and radiotherapy during 1999 to 2003. In multivariate analysis, age 30 Gy had significantly longer FFP compared with patients given 30 Gy had a significantly longer survival than those given a lesser dose (median of 2 months vs 8 months; P < .0001). Similarly, patients receiving a BED >39.0 Gy(10) also were found to have longer FFP (P = .03) and survival (median of 2 months vs 8 months; P < .0001) compared with those receiving a BED 30 Gy and a BED >39.0 Gy(10) were found to be associated with longer palliation. PMID- 17721995 TI - Role of high-molecular weight tropomyosins in TGF-beta-mediated control of cell motility. AB - Transforming growth factor beta1 (TGF-beta1) suppresses tumor development at early stages of cancer, but enhances tumor invasion and formation of metastasis. TGF-beta1-mediated tumor invasion is associated with epithelial to mesenchymal transition (EMT) and matrix proteolysis. The mechanisms of these TGF-beta1 responses in normal and tumor cells are not well understood. Recently, we have reported that TGF-beta1 increases expression of high-molecular weight tropomyosins (HMW-tropomyosins) and formation of actin stress fibers in normal epithelial cells. The present study investigated the role of tropomyosin in TGF beta1-mediated cell motility and invasion. We found that TGF-beta1 restricts motility of normal epithelial cells although it promotes EMT and formation of actin stress fibers and focal adhesions. Cell motility was enhanced by siRNA mediated suppression of HMW-tropomyosins. TGF-beta1 stimulated migration and matrix proteolysis in breast cancer MDA-MB-231 cells that express low levels of HMW-tropomyosins. Tet-Off-regulated expression of HMW-tropomyosin inhibited cell migration and matrix proteolysis without affecting expression of matrix metalloproteinases. Tropomyosin increased cell adhesion to matrix by enhancing actin fibers and focal adhesions. Finally, tropomyosin impaired the ability of tumor cells to form lung metastases in SCID mice. Thus, these results suggest that HMW-tropomyosins are important for TGF-beta-mediated control of cell motility and acquisition of the metastatic potential. PMID- 17721994 TI - Genetic and functional analysis of CHEK2 (CHK2) variants in multiethnic cohorts. AB - The CHEK2-1100delC mutation is recurrent in the population and is a moderate risk factor for breast cancer. To identify additional CHEK2 mutations potentially contributing to breast cancer susceptibility, we sequenced 248 cases with early onset disease; functionally characterized new variants and conducted a population based case-control analysis to evaluate their contribution to breast cancer risk. We identified 1 additional null mutation and 5 missense variants in the germline of cancer patients. In vitro, the CHEK2-H143Y variant resulted in gross protein destabilization, while others had variable suppression of in vitro kinase activity using BRCA1 as a substrate. The germline CHEK2-1100delC mutation was present among 8/1,646 (0.5%) sporadic, 2/400 (0.5%) early-onset and 3/302 (1%) familial breast cancer cases, but undetectable amongst 2,105 multiethnic controls, including 633 from the US. CHEK2-positive breast cancer families also carried a deleterious BRCA1 mutation. 1100delC appears to be the only recurrent CHEK2 mutation associated with a potentially significant contribution to breast cancer risk in the general population. Another recurrent mutation with attenuated in vitro function, CHEK2-P85L, is not associated with increased breast cancer susceptibility, but exhibits a striking difference in frequency across populations with different ancestral histories. These observations illustrate the importance of genotyping ethnically diverse groups when assessing the impact of low-penetrance susceptibility alleles on population risk. Our findings highlight the notion that clinical testing for rare missense mutations within CHEK2 may have limited value in predicting breast cancer risk, but that testing for the 1100delC variant may be valuable in phenotypically- and geographically-selected populations. PMID- 17721996 TI - Gene silencing of transcription factor Gli2 inhibits basal cell carcinomalike tumor growth in vivo. AB - Basal cell carcinoma (BCC) belongs worldwide to the most frequent malignancy among Caucasians. The understanding of the molecular mechanisms of BCC formation, which is a prerequisite for the development of efficient new therapies, is still incomplete. The formation of sporadic BCCs in the skin is associated with uncontrolled hedgehog signaling, and the transcription factor Gli2 has been identified as a key mediator or effector of this signaling. There is indication in the literature that preventing Gli2 function may inhibit BCC formation and growth in vivo; however, the mechanism is unclear and difficult to study in humans. Therefore, we used a mouse tumor allograft model to investigate the role of Gli2 in tumor formation. A constitutively Gli2 expressing mouse tumor cell line was stably transfected with Gli2-specific shRNA to induce Gli2 gene silencing or with control shRNA. Injecting the Gli2 gene silenced cells into nude mice for tumor formation we detected a strongly retarded tumor growth compared with control tumor cells. Investigating the mechanisms, we found that Gli2 gene silencing has led to the disruption of the tumor structure as demonstrated by staining tumor sections with hematoxylin. Two main reasons for the tumor destruction were identified. We found that apoptosis was markedly increased while vascularization was strongly decreased in these tumors. Thus, important functions of the transcription factor Gli2 in this tumor model are the prevention of apoptosis and the promotion of microvascularization. PMID- 17721997 TI - Vaccination trial with HPV16 L1E7 chimeric virus-like particles in women suffering from high grade cervical intraepithelial neoplasia (CIN 2/3). AB - Persistent infection with human papillomaviruses (HPV) is a prerequisite for the development of cervical cancer. Vaccination with virus-like particles (VLP) has demonstrated efficacy in prophylaxis but lacks therapeutic potential. HPV16 L1E7 chimeric virus-like particles (CVLP) consist of a carboxy-terminally truncated HPV16L1 protein fused to the amino-terminal part of the HPV16 E7 protein and self assemble by recombinant expression of the fusion protein. The CVLP are able to induce L1- and E7-specific cytotoxic T lymphocytes. We have performed a first clinical trial to gain information about the safety and to generate preliminary data on the therapeutic potential of the CVLP in humans. A randomized, double blind, placebo-controlled clinical trial has been conducted in 39 HPV16 mono infected high grade cervical intraepithelial neoplasia (CIN) patients (CIN 2/3). Two doses (75 mug or 250 mug) of CVLP were applied. The duration of the study was 24 weeks with 2 optional visits after another 12 and 24 weeks. The vaccine showed a very good safety profile with only minor adverse events attributable to the immunization. Antibodies with high titers against HPV16 L1 and low titers against HPV16 E7 as well as cellular immune responses against both proteins were induced. Responses were equivalent for both vaccine concentrations. A trend for histological improvement to CIN 1 or normal was seen in 39% of the patients receiving the vaccine and only 25% of the placebo recipients. Fifty-six percent of the responders were also HPV16 DNA-negative by the end of the study. Therefore, we demonstrated evidence for safety and a nonsignificant trend for the clinical efficacy of the HPV16 L1E7 CVLP vaccine. PMID- 17721998 TI - Expression of RANTES and MCP-1 in epithelial cells is regulated via LMP1 and CD40. AB - Epstein-Barr virus (EBV)-associated undifferentiated nasopharyngeal carcinoma (NPC) is characterized by a prominent nonneoplastic lymphoid stroma. The functional role of these inflammatory cells and the mechanism of their recruitment are not fully understood. In B-cells, the EBV-encoded latent membrane protein 1 (LMP1) can induce the expression of chemokines in an NF-kappaB dependent manner. We now show that LMP1 can induce the expression of RANTES and MCP-1 in an epithelial cell line, and that this effect is partially reversible by an inhibitor of NF-kappaB. Since tumor cells of virtually all NPCs show CD40 expression while many cases are LMP1-negative at the protein level, we also investigated the effect of CD40 signaling and demonstrate that CD40 stimulation can transiently induce RANTES and MCP-1 expression in LMP1-negative epithelial cells. In in situ hybridization only rare tumor cells showed expression of these chemokines unrelated to LMP1 expression, a pattern consistent with transient induction through CD40 signaling. Since RANTES and MCP-1 were also detected in the neoplastic cells of oral squamous cell carcinomas lacking a lymphoid stroma it remains uncertain to what extent these CC chemokines contribute to the attraction of inflammatory cells into the NPC microenvironment. PMID- 17721999 TI - Talcum powder, chronic pelvic inflammation and NSAIDs in relation to risk of epithelial ovarian cancer. AB - Chronic inflammation has been proposed as the possible causal mechanism that explains the observed association between certain risk factors, such as the use of talcum powder (talc) in the pelvic region and epithelial ovarian cancer. To address this issue we evaluated the potential role of chronic local ovarian inflammation in the development of the major subtypes of epithelial ovarian cancer. Factors potentially linked to ovarian inflammation were examined in an Australia-wide case-control study comprising 1,576 women with invasive and low malignant potential (LMP) ovarian tumours and 1,509 population-based controls. We confirmed a statistically significant increase in ovarian cancer risk associated with use of talc in the pelvic region (adjusted odds ratio 1.17, 95% CI: 1.01 1.36) that was strongest for the serous and endometrioid subtypes although the latter was not statistically significant (adjusted odds ratios 1.21, 95% CI 1.03 1.44 and 1.18, 95% CI 0.81-1.70, respectively). Other factors potentially associated with ovarian inflammation (pelvic inflammatory disease, human papilloma virus infection and mumps) were not associated with risk but, like others, we found an increased risk of endometrioid and clear cell ovarian cancer only among women with a history of endometriosis. Regular use of aspirin and other nonsteroidal anti-inflammatory drugs was inversely associated with risk of LMP mucinous ovarian tumours only. We conclude that on balance chronic inflammation does not play a major role in the development of ovarian cancer. PMID- 17722000 TI - Preparation of inhalable salbutamol sulphate using reactive high gravity controlled precipitation. AB - Reactive high gravity controlled precipitation (HGCP) was carried out to produce salbutamol sulphate (SS) particles suitable for inhalation. Aqueous solutions of free salbutamol base and sulphuric acid were mixed intensely inside a HGCP reactor to form the particles. Spray drying was employed to obtain dry powders. Physical properties of the powders were characterised by scanning electron microscopy, X-ray powder diffraction, thermal gravimetric analysis and dynamic water vapour sorption. Aerosol performance of the powders was measured using an Aeroliser connected to a multiple stage liquid impinger operating at 60 L/min. The results showed that the reactive HGCP powder, comprising primary SS sub micron particles (approximately 100 nm in width and approximately 500 nm in length) packed into loose spherical agglomerates of about 2 microm in diameter, is of the same polymorphic form as the raw crystalline material, has a high specific surface area (24.7 +/- 0.1 m(2)/g), but a low moisture content (0.2%) and low moisture uptake (1.4% at RH 90%). The aerosol performance of the reactive HGCP powder is excellent, showing FPF(loaded) and FPF(emitted) of 76 +/- 5% and 83 +/- 7%, respectively, with low capsule and device retention. In conclusion, reactive HGCP followed by spray drying is suitable to produce stable crystalline powders of salbutamol with enhanced inhalation properties. PMID- 17722001 TI - Structural characteristics and development of ampullary organs in Acipenser naccarii. AB - Ampullary organs of Acipenser naccarii sturgeons were examined by optical and electronic microscopy (transmission electron microscopy and scanning electron microscopy) from hatching until 1 month later when the juvenile phase is completely established. It was observed that, when A. naccarii begins to feed actively, the ultrastructural characteristics of ampullary organs already correspond to those of adult animals. These organs may, therefore, be functional and, together with taste buds, facilitate food search after exhaustion of yolk sac food reserves. Mature ampullary organs of A. naccarii are formed by an ampulla that communicates with the exterior by means of a short channel. These ampullae correspond to the sensory portion of these receptors and are formed by two cell types: receptor cells and support cells. Receptor cells present a kinocilium on their free surface and establish ribbon synapses with axon nerve endings that arise from the underlying conjunctive tissue. Support cells enclose receptor cells, bear stereocilia and occasional cilia, and are of a secretory nature. The mucus associated with ampullary organs mainly comprises neutral mucopolysaccharides, whereas mucopolysaccharides are usually acid in other fish groups. PMID- 17722002 TI - An evaluation of mathematical models for predicting skin permeability. AB - A number of mathematical models have been proposed for predicting skin permeability, mostly empirical and very few are deterministic. Early empirical models use simple lipophilicity parameters. The recent trend is to use more complicated molecular structure descriptors. There has been much debate on which models best predict skin permeability. This article evaluates various mathematical models using a comprehensive experimental dataset of skin permeability for 124 chemical compounds compiled from various sources. Of the seven models compared, the deterministic model of Mitragotri gives the best prediction. The simple quantitative structure permeability relationships (QSPR) model of Potts and Guy gives the second best prediction. The two models have many features in common. Both assume the lipid matrix as the pathway of transdermal permeation. Both use octanol-water partition coefficient and molecular size. Even the mathematical formulae are similar. All other empirical QSPR models that use more complicated molecular structure descriptors fail to provide satisfactory prediction. The molecular structure descriptors in the more complicated QSPR models are empirically related to skin permeation. The mechanism on how these descriptors affect transdermal permeation is not clear. Mathematically it is an ill-defined approach to use many colinearly related parameters rather than fewer independent parameters in multi-linear regression. PMID- 17722003 TI - Development of a high throughput equilibrium solubility assay using miniaturized shake-flask method in early drug discovery. AB - Increasingly, pharmaceutical and biotech companies have begun to realize the importance of obtaining solubility information in early drug discovery as it is one of the critical parameters for lead selection and optimization. This report introduces a high-throughput equilibrium solubility (HT-Eq sol) assay using a novel miniaturized shake-flask approach and streamlined HPLC analysis. The new HT Eq sol assay, validated and optimized via a test set of 85 marketed drugs and Novartis internal compounds, shows an excellent correlation to the conventional shake-flask thermodynamic solubility data generated in-house and the equilibrium solubility results reported in literature. It therefore offers a fast, reliable and cost-effective screening tool for solubility assessment in early drug discovery, allowing for prioritization of drug candidates using aqueous solubility in conjunction with other profiling information and efficacy data. Our work demonstrates that presence of a small amount of DMSO (0.5-5%) will result in significant overstimation of equilibrium solubility (up to 6 folds). In addition, monitoring of drug dissolution process using the current approach as well as the interplay between equilibrium solubility data and those from kinetic solubility are discussed. PMID- 17722004 TI - Identification of candidate prostate cancer biomarkers in prostate needle biopsy specimens using proteomic analysis. AB - Although serum prostate specific antigen (PSA) is a well-established diagnostic tool for prostate cancer (PCa) detection, the definitive diagnosis of PCa is based on the information contained in prostate needle biopsy (PNBX) specimens. To define the proteomic features of PNBX specimens to identify candidate biomarkers for PCa, PNBX specimens from patients with PCa or benign prostatic hyperplasia (BPH) were subjected to comparative proteomic analysis. 2-DE revealed that 52 protein spots exhibited statistically significantly changes among PCa and BPH groups. Interesting spots were identified by MALDI-TOF-MS/MS. The 2 most notable groups of proteins identified included latent androgen receptor coregulators [FLNA(7-15) and FKBP4] and enzymes involved in mitochondrial fatty acid beta oxidation (DCI and ECHS1). An imbalance in the expression of peroxiredoxin subtypes was noted in PCa specimens. Furthermore, different post-translationally modified isoforms of HSP27 and HSP70.1 were identified. Importantly, changes in FLNA(7-15), FKBP4, and PRDX4 expression were confirmed by immunoblot analyses. Our results suggest that a proteomics-based approach is useful for developing a more complete picture of the protein profile of PNBX specimen. The proteins identified by this approach may be useful molecular targets for PCa diagnostics and therapeutics. PMID- 17722005 TI - Delayed release tablet dissolution related to coating thickness by terahertz pulsed image mapping. AB - Delayed release dosage forms such as Asacol employ coatings that are engineered to breakdown and release the drug topically at the nominal pH of the lower intestinal tract. Asacol tablets were found to dissolve in an erratic fashion when they are dissolved in buffers below pH 7 which can occur naturally. In this study Terahertz pulsed imaging (TPI) was used to accurately map the coating thickness of a group of Asacol tablets that were subsequently dissolved using the USP method at pH 6.8. The mean dissolution times were found to correlate with the average coating thickness measured over all surfaces. Thickness values for a single randomly selected face did not correlate well with the dissolution results. The speed and ease of TPI mapping may make it an attractive replacement for wet dissolution testing both in product development and eventually for process analysis. PMID- 17722006 TI - Comprehensive cDNA study and quantitative transcript analysis of mutant OPA1 transcripts containing premature termination codons. AB - Autosomal dominant optic atrophy (adOA) is most commonly caused by mutations in the OPA1 gene. There is a considerable allelic heterogeneity among adOA associated OPA1 mutations, however these mutations have mostly been identified and studied only at the genomic DNA level. Here we report the identification of 22 novel OPA1 mutations and their analysis at the cDNA level along with 15 already known OPA1 mutations. We found that 18 of these mutations cause splice defects that involve either skipping of the adjacent exon or the activation of a cryptic splice site. We also observed a reduced level of the mutant transcript in several adOA subjects. Allele-specific quantification of the transcript steady state level was performed for 13 different OPA1 mutations applying pyrosequencing to a RT-PCR amplified cSNP (c.2109C>T) in OPA1. Using this new assay we could demonstrate that the majority of OPA1 mutations that lead to a premature termination codon (PTC) undergo nonsense-mediated mRNA decay (NMD). Mutant transcript levels were reduced between 1.25- and 2.5-fold and varied between PTC containing mutations, and between subjects. Our results emphasize the value of cDNA analysis in the characterization of OPA1 mutations and further strengthen the model of haploinsufficiency as a major pathomechanism in OPA1-associated adOA. PMID- 17722007 TI - The combination of PCR and serology increases the diagnosis of Pseudomonas aeruginosa colonization/infection in cystic fibrosis. AB - BACKGROUND: Early diagnosis of Pseudomonas aeruginosa colonization/infection in patients with cystic fibrosis (CF) using microbiological culturing methods may be difficult. Serology and polymerase chain reaction (PCR) may be useful techniques for early detection of P. aeruginosa in children with CF. METHODS: A cross sectional analysis comparing results obtained by three different methods for P. aeruginosa identification was performed in 87 CF patients with a mean age of 9.7 years. Microbiological culturing and PCR targeting the algD GDP mannose dehydrogenase gene of P. aeruginosa were performed in sputum or oropharyngeal swabs samples, and serum antibodies against three P. aeruginosa antigens (elastase, alkaline protease, and exotoxin A) were assessed once. RESULTS: It was possible to isolate P. aeruginosa by culture in samples from 42 patients (48.2%), while PCR was positive in 53 (60.9%) patients. Serology was positive in 38 patients (43.6%), with a higher positivity for elastase (37.9%), followed by alkaline protease (29.9%) and exotoxin A (19.5%). The difference among the three isolated methods was not statistically significant. The combination of PCR + serology was significantly superior to single methods, to PCR + culture and also to culture + serology. CONCLUSIONS: PCR identified a higher number of patients with P. aeruginosa than serology and conventional culture, but the difference did not reach statistical significance. Any of the combination methods that included PCR resulted in significantly statistical differences in relation to isolated microbiological or serology methods, but not to the PCR method alone, suggesting that PCR may be the main additive method for P. aeruginosa identification. PMID- 17722008 TI - Excitation and circular dichroism spectra of (-)-(3aS, 7aS)-2-chalcogena-trans hydrindans(Ch = S, Se, Te): SAC and SAC-CI calculations. AB - The ground and several electronic excited states of (3aS,7aS)-2-chalcogena-trans hydrindans were calculated by the symmetry adapted cluster (SAC) and SAC configuration interaction (SAC-CI) methods. Theoretical electronic excitation spectra and natural circular dichroism (CD) spectra were obtained for these compounds, and the calculated spectra showed good agreement with the experimental ones reported by Laur (Proceedings of the Third International Symposium on Organic Selenium and Tellurium compounds, Metz, France, 1979, pp. 219-299). For all the chalcogen compounds, the first singlet excited states are assigned to n sigma* and the other states are assigned to n-Rydberg in our calculations. It indicates that the spectra for the sulfide, selenide, and telluride are almost regarded as the analogues except for the red shifts of the band positions from the sulfide to the telluride. For the telluride, however, the experimental spectra have shapes that cannot be interpreted by the singlet excitations solely. Our calculations predict the triplet states that account for the spectral shapes, indicating importance of the spin-orbit interaction effects for the accurate reproduction of the experimental spectra of the telluride. PMID- 17722009 TI - Combined QM/MM and path integral simulations of kinetic isotope effects in the proton transfer reaction between nitroethane and acetate ion in water. AB - An integrated Feynman path integral-free energy perturbation and umbrella sampling (PI-FEP/UM) method has been used to investigate the kinetic isotope effects (KIEs) in the proton transfer reaction between nitroethane and acetate ion in water. In the present study, both nuclear and electronic quantum effects are explicitly treated for the reacting system. The nuclear quantum effects are represented by bisection sampling centroid path integral simulations, while the potential energy surface is described by a combined quantum mechanical and molecular mechanical (QM/MM) potential. The accuracy essential for computing KIEs is achieved by a FEP technique that transforms the mass of a light isotope into a heavy one, which is equivalent to the perturbation of the coordinates for the path integral quasiparticle in the bisection sampling scheme. The PI-FEP/UM method is applied to the proton abstraction of nitroethane by acetate ion in water through molecular dynamics simulations. The rule of the geometric mean and the Swain-Schaad exponents for various isotopic substitutions at the primary and secondary sites have been examined. The computed total deuterium KIEs are in accord with experiments. It is found that the mixed isotopic Swain-Schaad exponents are very close to the semiclassical limits, suggesting that tunneling effects do not significantly affect this property for the reaction between nitroethane and acetate ion in aqueous solution. PMID- 17722010 TI - Full configuration interaction calculation of the low lying valence and Rydberg states of BeH. AB - The all-electron full configuration interaction (FCI) vertical excitation energies for some low lying valence and Rydberg excited states of BeH are presented in this article. A basis set of valence atomic natural orbitals has been augmented with a series of Rydberg orbitals that have been generated as centered onto the Be atom. The resulting basis set can be described as 4s2p1d/2s1p (Be/H) + 4s4p3d. It allows to calculate Rydberg states up to n= {3,4,5} of the s, p, and d series of Rydberg states. The FCI vertical ionization potential for the same basis set and geometry amounts to 8.298 eV. Other properties such as FCI electric dipole and quadrupole moments and FCI transition dipole and quadrupole moments have also been calculated. The results provide a set of benchmark values for energies, wave functions, properties, and transition properties for the five electron BeH molecule. Most of the states have large multiconfigurational character in spite of their essentially single excited nature and a number of them present an important Rydberg-valence mixing that is achieved through the mixed nature of the particle MO of the single excitations. PMID- 17722011 TI - No association between common variants in glyoxalase 1 and autism spectrum disorders. AB - The autism spectrum disorders (ASDs) are complex diseases with a strong genetic component. Numerous candidate gene studies have tested association between various functional and positional candidate genes and autism, but no common variation predisposing for autism has been identified to date. It has been previously proposed, that glyoxalase 1 (GLO1) might be involved in the pathogenesis of autism as GLO1 protein polarity was significantly changed in the brains of autism patients compared to controls. GLO1 harbors a functional polymorphism that affects the polarity and the enzymatic activity of the protein. In the same study, this polymorphism showed a suggestive association to autism. To investigate whether common variants in GLO1 predispose to autism in the Finnish population, we have genotyped six polymorphisms in GLO1 in families with more than 230 individuals affected with ASDs and carried out both linkage and association analyses. We did not observe significant linkage or association between any SNP and ASDs. Therefore, we suggest that common variants in GLO1 are not significant susceptibility factors for ASDs in the Finnish population. PMID- 17722012 TI - Dissocial behavior, the 5HTTLPR polymorphism, and maltreatment in women with bulimic syndromes. AB - We recently reported that, among bulimic women, previously abused carriers of the 5HTTLPR S allele showed special propensities towards novelty seeking (implying recklessness or impulsivity) and interpersonal insecurity. We subsequently re analyzed our data, to examine the bearing of the 5HTTLPR polymorphism and prior sexual or physical maltreatment upon validated, higher-order personality-traits. Ninety women with bulimic syndromes were genotyped for 5HTTLPR "short" (S) and "long" (L(G) and L(A)) alleles, and then assessed for eating symptoms, history of sexual or physical abuse, and the higher-order personality traits Emotional Dysregulation, Dissocial Behavior, Inhibition, and Compulsivity. With a classification based on a biallelic model of 5HTTLPR (i.e., presence or absence of at least one S-allele copy), multiple regression indicated a significant proportion of variance in Dissocial Behavior to be explained by an abuse x genotype interaction-greater psychopathology occurring in abused S-allele carriers. A parallel analysis applying a triallelic model of 5HTTLPR (i.e., presence or absence of at least one copy of presumably low-function S or L(G) alleles) produced a similar pattern, but no statistically significant effect. The finding that bulimic 5HTTLPR S-allele carriers who are previously abused display elevations on Dissocial Behavior corroborates previous observations concerning phenomenological correlates of traumatic stress in 5HTTLPR S allele carriers. (c) 2007 Wiley-Liss, Inc. PMID- 17722013 TI - An association study of RGS4 polymorphisms with clinical phenotypes of schizophrenia in a Chinese population. AB - The regulator of G-protein signaling 4 (RGS4) has been suggested as a candidate gene for schizophrenia. However, following an initial positive report, subsequent association studies between RGS4 and schizophrenia have yielded inconclusive results. Also, few studies have investigated the association of RGS4 polymorphisms with the phenotypic subgroups of schizophrenia. To further clarify the role of RGS4 in this disease, we performed a case-control study (504 cases and 531 controls of Han Chinese descent) to examine the association of RGS4 with schizophrenia and with clinical and neurocognitive profiles. The four markers (SNPs 1, 4, 7, and 18) implicated in the original association study were genotyped. We detected significant association of four-marker haplotypes with schizophrenia (UNPHASED: global P = 0.037; PHASE: global P = 0.048). The haplotype G-G-G-G, which was implicated in at least three previous studies, was the major risk haplotype (UNPHASED: P = 0.019; PHASE: P = 0.010). Regarding the clinical phenotypes, the Wechsler Adult Intelligence Test (WAIS) information subtest score was associated with SNP4 genotypes (P = 0.001). PANSS total and global psychopathology scores were also associated with SNP4, but may not reliably reflect the general severity of disease as the scores may be affected by confounders like medication response. Our study provides further support for a role of RGS4 in the pathogenesis of schizophrenia. We identified G-G-G-G as the risk haplotype in our Chinese sample. The association with information subtest score suggests an effect of RGS4 on premorbid functioning, which may be related to neurodevelopmental processes. Further independent studies are required to verify our findings. PMID- 17722014 TI - Enantioselective analysis of citalopram and demethylcitalopram in human and rat plasma by chiral LC-MS/MS: application to pharmacokinetics. AB - Citalopram (CITA) is available as a racemic mixture and as a pure enantiomer. Its antidepressive action is related to the (+)-(S)-CITA and to the metabolite (+) (S)-demethylcitalopram (DCITA). In the present investigation, a method for the analysis of CITA and DCITA enantiomers in human and rat plasma was developed and applied to the study of pharmacokinetics. Plasma samples (1 ml) were extracted at pH 9.0 with toluene:isoamyl alcohol (9:1, v/v). The CITA and DCITA enantiomers were analyzed by LC-MS/MS on a Chiralcel OD-R column. Recovery was higher than 70% for both enantiomers. The quantification limit was 0.1 ng/ml, and linearity was observed up to 500 ng/ml plasma for each CITA and DCITA enantiomer. The method was applied to the study of the kinetic disposition of CITA administered in a single oral dose of 20 mg to a healthy volunteer and in a single dose of 20 mg/kg (by gavage) to Wistar rats (n = 6 for each time). The results showed a higher proportion of the (-)-(R)-CITA in human and rat plasma, with S/R AUC ratios for CITA of 0.28 and 0.44, respectively. S/R AUC ratios of DCITA were 0.48 for rats and 1.04 for the healthy volunteer. PMID- 17722015 TI - Synthesis of new chiral cis-3-hydroxyazetidines and their application in diethylzinc addition to aldehydes. AB - A new series of chiral cis-3-hydroxyazetidines have been prepared from (R)-1 phenylethylamine. They have excellent catalytic activities and enantiomeric selectivities in asymmetric addition of diethylzinc to aromatic aldehydes. PMID- 17722016 TI - Improving sensitivity in chiral supercritical fluid chromatography for analysis of active pharmaceutical ingredients. AB - Despite its status as the preferred method for routine enantiopurity analysis in pharmaceutical research, supercritical fluid chromatography (SFC) has historically been unsuited for the accurate and precise measurements required for release testing of active pharmaceutical ingredients (APIs) under current good manufacturing processes (cGMPs). Insufficient signal to noise, as compared to HPLC, has heretofore been the major limitation of the chiral SFC approach. We herein describe an investigation into the fundamental limitations and sources of noise in the SFC approach, identifying thermal, electronic, and mechanical sources of noise within the flow cell as key parameters contributing to reduced sensitivity. A variety of instrument modifications are explored, ultimately leading to the development of a new and improved flow cell and other instrument modifications that allow suitable sensitivity and accuracy to carry out GMP release testing for enantiopurity analysis using SFC. PMID- 17722018 TI - Development of the pulmonary vein. PMID- 17722017 TI - Uterine artery pseudoaneurysm: unusual cause of delayed postpartum hemorrhage. AB - We describe a case of uterine artery pseudoaneurysm in a 21-year-old woman with postpartum hemorrhage. This condition is easily diagnosed with duplex Doppler sonography and can be treated with embolization, but only if delayed postpartum hemorrhage is considered in the differential diagnosis. PMID- 17722019 TI - Promise and challenges of bioabsorbable stents. AB - Despite the development and progression of metallic stents, many concerns still remain because of their permanent nature. Although metallic stents are effective in preventing recoil and late restenosis after coronary angioplasty, they continue to have limitations such as stent thrombosis and mismatch of the stent to the vessel size. Thus, the concept of bioabsorbable stents has emerged as an alternative to permanent metal stents. This review will outline concepts, material designs, preclinical, and initial clinical experimental studies with bioabsorbable stents. PMID- 17722020 TI - Stent thrombosis after sirolimus- and paclitaxel-eluting stent implantation in daily clinical practice: analysis of a single center registry. AB - OBJECTIVES: To evaluate stent thrombosis (ST) rate after sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES) implantation in daily clinical practice. BACKGROUND: The safety profile of drug-eluting stents (DES) was predominantly determined in randomized clinical trials with narrow inclusion criteria. Concerns about ST have been raised in unselected patients treated with DES. METHODS: We prospectively evaluated 867 patients undergoing DES implantation, 618 patients with SES, and 249 with PES, in a single academic center. RESULTS: Multivessel disease was present in 72% of patients, multivessel stenting was performed in 17%, long (>18 mm) lesions were treated in 30%, and multiple stents per lesion were needed in 31%. On average, 1.7 +/- 0.8 stents per patient were implanted (stented segment length: 32 +/- 25 mm/vessel). IIb/IIIa inhibitors were used in 7.5%. Intravascular ultrasound (IVUS) guidance was employed in 65% of SES and 50% of PES implantations, and the procedural success rate was 100% in SES and 99% in PES cases. Six-month follow-up was performed in all patients, whereas one-year follow-up was completed in 87% patients of the SES group and in 95% of the PES group. We considered that ST occurred when angiographic evidence of thrombus was available, or when patients experienced sudden cardiac death or either ST elevation or non-ST-elevation myocardial infarction (MI) through the 12-month follow-up period. The overall incidence of ST was 0.9% (0.4% in SES and 2% in PES, P = 0.03). Of the eight ST, two (25%) were acute, four (50%) subacute, one (12.5%) was a late event, and one (12.5%) a very late event. Seven ST were confirmed by angiography. No IVUS guidance was used in 4/8 (50%) ST patients, while antiplatelet therapy was prematurely discontinued in 3/8 (37.5%). Among ST patients, mortality and nonfatal MI rates were 25% and 37.5%, respectively. No ST was diagnosed between 6 and 12 months, while one very late thrombosis occurred at 15 months. CONCLUSIONS: The incidence of ST after DES use in daily clinical practice is low and similar to that observed in randomized clinical trials. PMID- 17722022 TI - Sperm release from oviduct epithelial binding is controlled hormonally by peri ovulatory graafian follicles. AB - To avoid inappropriate conclusions being drawn from the extensive use of in vitro preparations of sperm-oviduct epithelial binding, it is recalled that events in the genital tract of mammals are regulated by the gonads, primarily by their changing secretion of steroid hormones. Key observations from in vivo models are used to emphasise the dynamic interactions between viable sperm cells and the caudal (distal) portion of the oviduct isthmus, the site of the functional sperm reservoir. These include (1) pre-ovulatory arrest and epithelial binding of intact sperm cells and thereby suppression of completion of capacitation, (2) peri-ovulatory activation and release from binding of discrete sub-populations of competent spermatozoa, and (3) post-ovulatory liberation of large numbers of spermatozoa. These observations underline the influence of endocrine regulation of sperm binding and release by peri-ovulatory Graafian follicles, a point brought out by the enhanced sperm release prompted by diverse treatments with solutions of progesterone. In the light of this evidence, the suitability of in vitro preparations for clarifying physiological events should be questioned, especially if myosalpingeal catecholamines diffusing out of the autonomic nervous system contribute to sperm activation and/or release. None of this is to infer that sperm cells themselves are without influence on their epithelial binding reaction(s). Nor is it to suggest that in vitro models of sperm-oviduct binding are without relevance to the development of sperm evaluation technologies. However, pre-ovulatory sperm-epithelial binding and a regulated peri-ovulatory release should be seen as vital tactics in the overall strategy of achieving successful monospermic fertilisation. PMID- 17722021 TI - Resolution of migraine by transcatheter patent foramen ovale closure with Premere Occlusion System in a preliminary series of patients with previous cerebral ischemia. AB - BACKGROUND: Transcatheter closure of PFO with nitinol devices may be problematic in young patients with migraine due the risk of late erosions. Alternative devices with less amount of metal as the last generation devices may be preferable in such cases. We present the results of transcatheter closure of PFO with the last generation Premere Occlusion System device in a preliminary series of young adults with migraine and previous cerebral ischemia. METHODS: During a 12-month period (January 31, 2006 to December 31, 2006) 26 patients (18 female and 8 male, mean age 40 +/- 3.7 years) with previous stroke and severe disabling migraine were referred to our center for transcatheter closure of PFO. Migraine disability assessment score (MIDAS) was used to assess MHA incidence and severity. Patients were selected for Premere occlusion system (absence of atrial septal aneurysm and length >15 mm) on the basis of presence/absence of right and left bulging atrial septal aneurysm and length of PFO channel (<15 mm or >15 mm) on transesophageal echocardiography. Transesophageal echocardiography and transcranial Doppler were performed at 1 month, transthoracic echocardiography and cerebral magnetic resonance imaging at 6 and 12 months. Cardiologic and neurological visit was scheduled at 1, 6, and 12 months with MIDAS questionnaire administration. RESULTS: Ten patients (2 males, mean age 32 +/- 7.6 years, mean MIDAS score 38.9 +/- 5.8) underwent transcatheter PFO closure with the Premere occlusion system. Mean fossa ovalis diameters by ICE measurement was 20.6 +/- 3.1 mm. Thus, two 20-mm and eight 25-mm Premere devices were implanted. The procedure was successful in all of the patients with no perioperative and in-hospital complications. After a mean follow-up of 10.9 +/- 5.8 months, all patients were free from migraine symptoms (mean MIDAS score 2.9 +/- 1.9) with PFO complete closure in all patients on transesophageal and transcranial Doppler ultrasound. CONCLUSION: While waiting for larger studies evaluating the impact of new generation devices in curing PFO-related migraine, this preliminary anecdotal series suggests that the Premere occlusion system may be an effective and safe device for young patients with previous cerebral ischemia and migraine at least in the midterm period. PMID- 17722023 TI - The ADHD resource: creation of an online tool for attention deficit hyperactivity disorder information and research. AB - With the ever growing quantity of information generated by research into attention deficit hyperactivity disorder (ADHD) and the growth of international cooperation and collaboration, a need has arisen for a simple reference resource. The ADHD Resource was created to be this tool. It has been designed to act as the first point of reference for researchers in the field. It has also been created to facilitate the collaborative effects amongst the research groups. PMID- 17722024 TI - A coalescent simulation of marker selection strategy for candidate gene association studies. AB - Recent efforts have focused on the challenges of finding alleles that contribute to health-related phenotypes in genome-wide association studies. However, in candidate gene studies, where the genomic region of interest is small and recombination is limited, factors that affect the ability to detect disease susceptibility alleles remain poorly understood. In particular, it is unclear how varying the number of markers on a haplotype, the type of marker (e.g., single nucleotide polymorphism (SNP), short tandem repeat (STR)), including the causative site (cs) as a genetic marker, or population demographics influences the power to detect a candidate gene. We evaluated the power of association tests using coalescent-modeled computer simulations. Results show that an effective number of markers on a haplotype is dependent on whether the cs is included as a marker. When the analyses include the cs, highest power is achieved with a single marker association test. However, when the cs is excluded from analyses, the addition of more nonfunctional SNPs on the haplotype increases power to a certain point under most scenarios. We find a rapidly expanding population always has lower power compared to a population of constant size; although utilizing markers with a frequency of at least 5% improves the chance of detecting an association. Comparing the mutational properties of a nonfunctional SNP versus an STR, multi allelic STRs provide more or comparable power than a bi-allelic SNP unless SNP frequencies are constrained to 10% or more. Similarly, including an STR with SNPs on a haplotype improves power unless SNP frequencies are 5% or more. PMID- 17722025 TI - Evidence of normal hearing laterality in familial schizophrenic patients and their relatives. AB - Dichotic listening (DL) has been used as a tool to investigate possible left cerebral dysfunction in schizophrenia. However, the wide range of DL tests (e.g., words, emotions, sentences) as well as patient groups ("heterogeneity") has introduced several confounders. Assessing relatives of patients with schizophrenia may overcome some of these problems, and may be more useful in determining if loss of functional cerebral laterality in schizophrenia is a state or a trait phenomenon. The fused consonant-vowel DL test was administered to 114 subjects: 20 individuals with familial schizophrenia, 42 of their healthy relatives, and 52 healthy volunteers. We did this to investigate whether the normal language processing asymmetry-a right ear advantage (REA)-is present, and whether it could serve as a marker for genetic liability. General performance accuracy level was lower in schizophrenia patients and their relatives but the expected REA was present in all groups. Adjusting for age, accuracy, and obligate status made no difference. In conclusion, familial schizophrenic patients and their relatives have normal REA and hearing laterality on the fused DL test. PMID- 17722026 TI - Systematic studies on the computation of nuclear magnetic resonance shielding constants and chemical shifts: the density functional models. AB - We present a systematic density functional investigation on the prediction of the 13C, 15N, 17O, and 19F NMR properties of 23 molecules with 21 density functionals. Extensive comparisons are made for both 13C magnetic shieldings and chemical shifts with respect to the gas phase experimental data and the best CCSD(T) results. We find that the OPBE and OPW91 exchange-correlation functionals perform significantly better than some popular functionals such as B3LYP and PBE1PBE, even surpassing, in many cases, the standard wavefunction-based method MP2. Further analysis has been performed to explore the individual role played by various exchange and correlation functionals. We find that the B88 and PBE exchange functionals have a too strong tendency of deshielding, leading to too deshielded magnetic shielding constants; whereas the OPTX exchange functional performs remarkably well. We claim that the main source of error arises from the exchange functional, but correlation functional also makes important contribution. We find that the correlation functionals may be grouped into two classes. class A, such as LYP and B98, leads to deshielded NMR values, deteriorating the overall performance; whereas class B, such as PW91 and PBE, generally increases the absolute shieldings, which complements the exchange functionals, leading to improved results in the calculation of NMR data. PMID- 17722027 TI - Theoretical investigation on the protonation reactions and products of the stable [N,C,C,S] isomers. AB - A theoretical study on the protonation system of [N,C,C,S], [H,N,C,C,S]+, was performed at the B3LYP/6-311++G(d,p) and CCSD(T)/6-311++G(2df,2p) (single point) levels of theory. On the doublet [H,N,C,C,S]+ surface, 24 species were located as energy minima and 10 of them were considered as kinetically stable species. The species HNCCS+ with 2A' state and a shallow W-shaped skeleton was predicted to be the global minimum and kinetically the most stable species, being in good agreement with previous experimental findings. Furthermore, the protonation reactions of the stable [N,C,C,S] isomers were investigated in detail. The calculation results indicated that the [N,C,C,S] isomers may be significantly stabilized upon protonation. Finally, the possible covalent structures of the [H,N,C,C,S]+ isomers with considerable stability were briefly discussed. PMID- 17722028 TI - Effect of Rds abundance on cone outer segment morphogenesis, photoreceptor gene expression, and outer limiting membrane integrity. AB - We examined the molecular, structural, and functional consequences on cone photoreceptors of the neural retinal leucine zipper knockout (Nrl(-/-)) mice when only one allele of retinal degeneration slow (Rds) is present (Rds(+/-)/Nrl(-/ )). Quantitative RT-PCR and immunoblot analysis were used to assess the expression levels of several phototransduction genes; electroretinography was used to assess quantitatively the retinal responsiveness to light; and immunohistochemistry and ultrastructural analysis were used to examine retinal protein distribution and morphology, respectively. In Rds/Nrl double-null mice, S cones form dysmorphic outer segments that lack lamellae and fail to associate properly with the cone matrix sheath and the outer limiting membrane. In Rds(+/ )/Nrl(-/-) mice, cones form oversized and disorganized outer segment lamellae; although outer limiting membrane associations are maintained, normal interactions with cone matrix sheaths are not, and photoreceptor rosette formation is observed. These retinas produce significantly higher photopic a-wave and b-wave amplitudes than do those of Rds(-/-)/Nrl(-/-) mice, and the levels of several cone phototransduction genes are significantly increased coincidently with the presence of Rds and partial lamellae formation. Thus, as in rod photoreceptors, expression of only one Rds allele is unable to support normal outer segment morphogenesis in cones. However, cone lamellae assembly, albeit disorganized, concomitantly permits outer limiting membrane association, and this appears to be linked to photoreceptor rosette formation in the rodless (cone-only) Nrl(-/-) retina. In addition, photoreceptor gene expression alterations occur in parallel with changes in Rds levels. PMID- 17722029 TI - Cholinergic innervation of the zebrafish olfactory bulb. AB - A number of fish species receive forebrain cholinergic input but two recent reports failed to find evidence of cholinergic cell bodies or fibers in the olfactory bulbs (OBs) of zebrafish. In the current study we sought to confirm these findings by examining the OBs of adult zebrafish for choline acetyltransferase (ChAT) immunoreactivity. We observed a diffuse network of varicose ChAT-positive fibers associated with the nervus terminalis ganglion innervating the mitral cell/glomerular layer (MC/GL). The highest density of these fibers occurred in the anterior region of the bulb. The cellular targets of this cholinergic input were identified by exposing isolated OBs to acetylcholine receptor (AChR) agonists in the presence of agmatine (AGB), a cationic probe that permeates some active ion channels. Nicotine (50 microM) significantly increased the activity-dependent labeling of mitral cells and juxtaglomerular cells but not of tyrosine hydroxlase-positive dopaminergic neurons (TH(+) cells) compared to control preparations. The nAChR antagonist mecamylamine, an alpha7-nAChR subunit specific antagonist, calcium-free artificial cerebrospinal fluid, or a cocktail of ionotropic glutamate receptor (iGluR) antagonists each blocked nicotine stimulated labeling, suggesting that AGB does not enter the labeled neurons through activated nAChRs but rather through activated iGluRs following ACh stimulated glutamate release. Deafferentation of OBs did not eliminate nicotine stimulated labeling, suggesting that cholinergic input is primarily acting on bulbar neurons. These findings confirm the presence of a functioning cholinergic system in the zebrafish OB. PMID- 17722030 TI - Developmental changes in cellular prion protein in primate visual cortex. AB - Cellular prion protein (PrP(c)) is a cell surface glycoprotein highly expressed in neurons, and a protease-resistant conformer of the protein accumulates in the brain parenchyma in prion diseases. In human prion diseases, visual cortex and visual function can be affected. We examined both the levels and the localization of PrP(c) in developing visual cortex of the common marmoset. Western blot analysis showed that PrP(c) increased from the day of birth through adulthood, and this increase correlated with the progression of synapse formation. Immunohistochemistry showed that PrP(c) was present in fiber tracts of the neonate, and this immunoreactivity was lost with maturation. Within the neuropil, the laminar distribution of PrP(c) changed with age. In the neonate, PrP(c) immunoreactivity was strongest in layer 1, where the earliest synapses form. At the end of the first postnatal week, layer 4C, as identified by its strong cytochrome oxidase activity, was noticeably lighter in terms of PrP(c) immunoreactivity than the adjacent layers. The contrast between the strong immunoreactivity in both supragranular and infragranular layers and weak immunoreactivity in layer 4C increased with age. Layers 2/3 and 5 contained more intense PrP(c) immunoreactivity; these layers receive thalamic input from the koniocellular division of the LGN, and these layers of the LGN also had strong PrP(c) immunoreactivity. Together, these results provide evidence for PrP(c) localization in an identified functional pathway and may shed some light on prion disease pathogenesis. PMID- 17722031 TI - Differential expression of phosphacan/RPTPbeta isoforms in the developing mouse visual system. AB - The chondroitin sulfate proteoglycan DSD-1-PG/phosphacan represents one of four splice variants of receptor-protein-tyrosine-phosphatase-beta/zeta (RPTPbeta/zeta). This receptor is expressed by glial cells and occurs in two isoforms, RPTPbeta(long) and RPTPbeta(short). The secreted forms phosphacan and phosphacan short isoform (PSI) bind to extracellular matrix and adhesion molecules and might mediate astroglial effects on neuronal differentiation. Phosphacan and RPTPbeta(long) both carry the DSD-1 epitope, a glycosaminoglycan modification that is involved in stimulating neurite outgrowth of embryonic rat mesencephalic and hippocampal neurons in a polycationic environment. Additionally, phosphacan inhibits neurite outgrowth of embryonic DRG neurons in the presence of laminin. In the light of these functional properties we examined the expression patterns of the DSD-1 epitope and phosphacan isoforms in the developing mouse visual system. During retinal development the DSD-1 epitope appears around embryonic day (E)13, peaks around postnatal day (P)6, and is downregulated from P9 to adolescence. By comparison, the phosphacan core protein is first detectable at E12, reaches maximal levels around P14, and persists, although at lower levels, to adulthood. The DSD-1 epitope is restricted to the nerve fiber and the inner plexiform layers. In contrast, the phosphacan core protein immunoreactivity extends from the nerve fiber layer to the outer plexiform layer. The level of expression of the phosphacan/RPTPbeta gene was investigated by reverse-transcriptase polymerase chain reaction. These experiments suggest that there is a shift in the expression patterns of the different phosphacan/RPTPbeta isoforms during late embryonic and postnatal development. In situ hybridization experiments support the conclusion that at least one of the phosphacan/RPTPbeta isoforms in the retina is expressed by neurons. PMID- 17722032 TI - Distribution of the voltage-gated sodium channel Na(v)1.7 in the rat: expression in the autonomic and endocrine systems. AB - It is generally accepted that the voltage-gated, tetrodotoxin-sensitive sodium channel, Na(V)1.7, is selectively expressed in peripheral ganglia. However, global deletion in mice of Na(V)1.7 leads to death shortly after birth (Nassar et al. [2004] Proc. Natl. Acad. Sci. U. S. A. 101:12706-12711), suggesting that this ion channel might be more widely expressed. To understand better the potential physiological function of this ion channel, we examined Na(V)1.7 expression in the rat by in situ hybridization and immunohistochemistry. As expected, highest mRNA expression levels are found in peripheral ganglia, and the protein is expressed within these ganglion cells and on the projections of these neurons in the central nervous system. Importantly, we found that Na(V)1.7 is present in discrete rat brain regions, and the unique distribution pattern implies a central involvement in endocrine and autonomic systems as well as analgesia. In addition, Na(V)1.7 expression was detected in the pituitary and adrenal glands. These results indicate that Na(V)1.7 is not only involved in the processing of sensory information but also participates in the regulation of autonomic and endocrine systems; more specifically, it could be implicated in such vital functions as fluid homeostasis and cardiovascular control. PMID- 17722033 TI - Increased host neuronal survival and motor function in BMT Parkinsonian mice: involvement of immunosuppression. AB - We examined the potential of bone marrow transplantation (BMT) to rescue dopaminergic neurons in a mouse model of Parkinson's disease (PD). A BMT from mice transgenic for green fluorescent protein (GFP(+)) given either before or after administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) led to the accumulation of transplanted adult GFP(+) bone-marrow-derived cells (BMDC) in the substantia nigra, where dopaminergic neurodegeneration occurs in PD. Post-BMT, mice exposed to MPTP had substantially greater numbers of endogenous tyrosine hydroxylase-positive neuronal cell bodies in the substantia nigra and increased dopamine transporter-positive projections into the striatum compared to controls. Moreover, motor function was restored to normal within 1 month post-MPTP in BMT-treated mice assayed by a rotarod behavioral test. The effect of BMT on PD was indirect, as no evidence of BMDC fusion with or transdifferentiation into dopaminergic neurons was observed. BMDC activated by BMT or associated factors could play a trophic role in rescuing damaged cells. Alternatively, the beneficial effects of BMT are due to immunosuppression reflected by a reduction in the proportion of T-cells and a reduction of T-cell proliferation in BMT mice. These findings highlight that when immunosuppression is required for transplantation studies, the amelioration of symptoms may not be due to the transplant itself. Further, they suggest that the immune system plays a role in the development of characteristics typical of PD. PMID- 17722034 TI - Coexpression of prodynorphin and corticotrophin-releasing hormone in the rat central amygdala: evidence of two distinct endogenous opioid systems in the lateral division. AB - The lateral subdivision of the central nucleus of the amygdala (CeA) comprises two groups of gamma-aminobutyric acid (GABA) neurons that express corticotrophin releasing hormone (CRH) and enkephalin. Regulation of the expression and release of these neuropeptides by glucocorticoids and other factors has been suggested to have a regulatory function on the diverse somatic, autonomic, and neuroendocrine responses that are coordinated by the CeA. Because another opioid peptide, dynorphin, has been reported to be also expressed by neurons in the lateral CeA, this study examined the neuronal expression of this kappa-opioid (KOP) receptor preferring ligand by using immunohistochemistry for the precursor peptide prodynorphin. Prodynorphin neurons in the extended amygdala were observed mostly in the medial and central regions of the lateral CeA and the oval of the bed nucleus of the stria terminalis (BST). About one-third of the prodynorphin neurons in the CeA coexpressed CRH, whereas no coexpression with CRH was detected in the BST. Prodynorphin was not expressed by calbindin neurons in the medial part of the lateral CeA, and indirect evidence suggested that it was not expressed by enkephalin neurons. Coexpression of prodynorphin in extrahypothalamic CRH neurons in the CeA could provide an anatomical basis for regulation of the stress responses and other CRH-related functions by the brain dynorphin/KOP receptor system. PMID- 17722035 TI - Neuroprotective effects of resident microglia following acute brain injury. AB - Microglia quickly react to various neurodegenerative processes by producing cytokines and eliminating cellular debris via phagocytosis. These events are also associated with an increased proliferation of microglia, which derive from resident progenitors and those present in the bone marrow. However, it is not clear whether the innate immune response by resident or newly differentiated microglia is beneficial or detrimental to the central nervous system. The aim of this study was to determine the impact of an altered immune response following acute excitotoxicity. Sodium nitroprusside (SNP) or kainic acid (KA) was administered in the brain of various groups of mice, and the extent of neurodegeneration, myelin damage, and inflammation was evaluated within a period of 2 weeks. We used synthetic glucocorticoid (GC), myeloid differentiation factor 88 (MyD88)-deficient mice to suppress nuclear factor kappaB (NF-kappaB) signaling and transgenic mice that express the thymidine kinase (TK) protein under the control of the CD11b promoter to determine the role of proliferating and infiltrating microglia in acute models of brain injury. Neurodegeneration was more extensive in GC-treated and MyD88-deficient mice, suggesting that NF-kappaB signaling and microglia activation are potent neuroprotective mechanisms in the presence of SNP. KA was also highly toxic to neurons of the amygdala in MyD88 knockout mice but not in their WT littermates. Although bone marrow-derived cells are clearly attracted to neurodegenerative areas, preventing their infiltration and differentiation did not affect the extent of SNP-related damage. These data indicate that MyD88/NF-kappaB signaling in resident non-proliferating microglia plays a critical role by restricting damage during acute excitotoxicity. PMID- 17722036 TI - The AST petal dedicated bifurcation stent: first-in-human experience. AB - The aim of this first-in-human study was to evaluate the feasibility and safety of the novel AST petal side-access bifurcation stent. Outcomes following percutaneous coronary intervention for bifurcations remain inferior to those of nonbifurcated lesions. Even with drug-eluting stents, restenosis occurs especially at the side-branch (SB) ostium. The petal stent uniquely deploys strut elements into the SB, supporting the ostium and carina. The primary endpoint of this 13-patient prospective registry was in-hospital major adverse cardiac events (MACE). Secondary end points included acute minimum lumen diameter (MLD) at the SB ostium, lesion success, device success, procedural success, 30-day MACE, and 4 month SB ostial MLD. The study lesion was successfully treated in 13 patients with the study stent being successfully implanted in 12. Target lesions were left anterior descending coronary artery in nine subjects, left circumflex in three, and right coronary artery in one. In-hospital MACE were limited to two non-Q-wave myocardial infarctions. In-stent main branch MLD increased from a mean of 0.63 +/ 0.45 mm to 2.61 +/- 0.47 mm at the index procedure and for this initial bare metal version of the stent, 4-month mean MLD measured 1.02 +/- 0.42 mm and there was target vessel revascularization on two patients. The feasibility of safely deploying this first-generation petal stent was demonstrated in selected patients with challenging coronary bifurcation lesions. It is a promising platform for drug delivery, with unique scaffolding of the side-branch ostium. PMID- 17722037 TI - Heterogeneity of atherosclerotic plaque characteristics in human coronary artery disease: a three-dimensional intravascular ultrasound study. AB - OBJECTIVES: The objective of this study was to describe the intraplaque variability of coronary atherosclerosis in humans. BACKGROUND: Atherosclerosis is a heterogeneous process. The degree and patterns of intraplaque heterogeneity are not well described. This study uses 3D intravascular ultrasound (IVUS) to examine variability in individual atherosclerotic plaques in human coronary arteries. METHODS: IVUS images of 170 coronary plaques in 98 patients were evaluated. Each plaque was divided into proximal, middle, and distal sections. Quantitative and qualitative analyses were performed for each section using a dedicated 3D IVUS protocol. Intralesion heterogeneity was assessed between sections. RESULTS: Heterogeneity in composition was observed in most plaques (89%). The pattern of remodeling was heterogeneous in 23% of lesions. External elastic membrane (EEM) areas demonstrated an average percent deviation of 28.9% +/- 15.5%. Positive remodeling was associated with longer lesions (>> median length of 12.7 mm) (P = 0.031). Soft and calcific sections had a smaller mean EEM area (P = 0.034). Calcific lesions had a smaller mean lumen area (P = 0.027) and a greater percent plaque burden (PPB) (P = 0.001). Neither the location within the vessel or within the plaque was associated with plaque morphology. Greater qualitative heterogeneity was found in patients presenting with acute coronary syndrome (P < 0.001). CONCLUSIONS: Our results demonstrate a high degree of heterogeneity in composition and morphological features within individual atherosclerotic plaques in human coronary arteries. Intraplaque heterogeneity represents a challenge for imaging protocols correlating plaque features with cardiovascular events and for the development of future therapeutic options. PMID- 17722038 TI - Heterogeneity of atherosclerotic plaque characteristics in human coronary artery disease: a three-dimensional intravascular ultrasound study. PMID- 17722039 TI - Thoracic radiotherapy in patients with lymphoma and restenosis after coronary stent placement. AB - OBJECTIVES: The aim of this study was to assess the incidence of restenosis after coronary stenting in patients with lymphoma treated with thoracic radiation. BACKGROUND: Patients with Hodgkin lymphoma treated with thoracic radiation have an increased incidence of coronary artery disease (CAD). The incidence of restenosis after percutaneous coronary interventions is completely unknown. METHODS: This study included 12,626 consecutive patients with CAD treated with coronary stenting during a 10-year period. Within this cohort, three subgroups of patients were assessed: patients with lymphoma and previous thoracic radiation (15 patients), patients with lymphoma without thoracic radiation (7 patients) and patients without lymphoma or previous thoracic radiation (control group; 12,604 patients). Coronary stenting was performed after a median [25th; 75th percentiles] of 8 years [4; 17] after thoracic radiation. The primary end point of the study was restenosis at 6-month coronary angiography. RESULTS: Six-month coronary angiography was performed in 14 patients (93%) in the group with lymphoma and radiation, 6 patients (86%) in the group with lymphoma without radiation and 10,032 patients (80%) in the control group (P = 0.38). Angiographic restenosis was found in 12 patients (85.7%) in the group with lymphoma and radiation, 1 patient (16.7%) in the group with lymphoma without radiation and 2,555 patients (25.5%) in the control group (P < 0.001). Multiple logistic regression identified thoracic radiation as an independent predictor of coronary restenosis (odds ratio 21.7, 95% confidence interval, 4.7-100.9, P < 0.001). CONCLUSIONS: Patients with lymphoma treated with thoracic radiation have an increased risk of restenosis after coronary artery stenting. PMID- 17722040 TI - Ionizing radiation and the coronary arteries: the plot is thickening! PMID- 17722041 TI - Sirolimus-eluting stent implantation for treatment of proximal left anterior descending coronary artery lesions: long-term outcome and predictors of adverse cardiac events. AB - OBJECTIVES: Acute and long-term results after sirolimus-eluting stent (SES) implantation of proximal left anterior descending coronary artery (LAD) disease were evaluated. BACKGROUND: Although SES has been used increasingly for the treatment of LAD disease, data regarding their safety and efficacy in a real world population are limited. METHODS: We investigate the short- and long-term results in 966 patients who underwent SES implantation for stenosis of proximal LAD. RESULTS: The procedural success rate was 97.6%, and procedural non-Q-wave myocardial infarction (MI) rate was 14.5%. In-hospital major complications occurred in five patients (0.5%), including three deaths and two Q-wave MIs. During follow-up (20.4 +/- 8.9 months), there were 16 deaths (1.7%; 10 cardiac, 6 noncardiac), 2 Q-wave MIs, and 22 target lesion revascularizations (2.3%). Late stent thrombosis occurred in two patients (0.2%), 14 and 23 months after the procedure. The event-free survival rates for cardiac death/Q-wave MI were 98.6% +/- 0.4% at 1 year and 97.8% +/- 0.6% at 2 years. The cumulative probabilities of survival without major adverse cardiac events (MACE) were 96.7% +/- 0.6% at 1 year and 95.4% +/- 0.8% at 2 years. In multivariate analysis, stented length (HR 1.04, 95%CI 1.01-1.07, P = 0.009) and infarct-related artery (HR 5.18, 95%CI 1.09 24.64, P = 0.039) were independently related to cardiac death/Q-wave MI. In addition, stented length (HR 1.04, 95%CI 1.02-1.06, P < 0.001) and left ventricular dysfunction (HR 2.66, 95%CI 1.07-6.63, P = 0.036) were significant independent predictors of MACE. CONCLUSIONS: SES implantation for proximal LAD disease appears safe and effective in a real-world population, and the independent predictors of MACE included stented length and left ventricular dysfunction. PMID- 17722042 TI - Comment on "Percutaneous left ventricular assist device complicated by a patent foramen ovale: importance of identification and management". PMID- 17722043 TI - Anti-platelet and anti-thrombotic approaches in patients undergoing percutaneous coronary intervention. AB - Over the past three decades, there has been a tremendous increase in the use of percutaneous coronary interventions (PCI) for the treatment of patients with atherosclerotic coronary artery disease. However, PCI causes disruption of atherosclerotic plaque and denudation of the endothelium, leading to stimulation of platelet aggregation and activation of the coagulation cascade. Therefore, anti-platelet and anti-thrombotic agents have a pivotal role as adjuncts before, during and after PCI, in order to minimize the risk of procedural ischemic complications, such as myocardial infarction, stent thrombosis, and various degrees of myonecrosis. The current article presents a comprehensive review of the evolution of current anti-platelet and anticoagulation regimens used in the setting of PCI. It starts with a summary of the current perspective of the coagulation process along with platelet activation and aggregation. The review then focuses specifically on individual anti-platelet and anti-thrombotic drugs including their mechanism of action and the scientific evidence which led to their use in PCI. Finally, we present summary recommendations from the AHA/ACC guidelines for individual anticoagulant and anti-platelet regimens given peri PCI. PMID- 17722044 TI - Community survey of primary dystonia in the city of Kolkata, India. AB - An epidemiological study on dystonia has not been reported from India. As part of a major study to find out the prevalence of major neurological disorders in the large urban city of Kolkata, Eastern India, we planned to determine the prevalence of primary dystonia. The study design was a cross-sectional study of a sample population obtained through stratified random selection and conducted in a two-stage procedure of screening by a nonprofessional team followed by confirmation of screened positive cases by the study neurologist. A total population of 52,377 was screened, and 29 subjects with dystonia were diagnosed. Out of them 23 subjects had primary dystonias [crude prevalence rate (CPR), 43.91/100,000; 95% confidence interval (CI), 28.41-64.81; age-standardized rates to world standard population, 49.06 (95% CI,31.74-72.41)] and all cases were focal type and predominantly of limb dystonia variety. Mean onset of dystonias were earlier in women (43.5 years) as compared to men (46.6 years). Thus our study on primary dystonia shows higher prevalence when compared with that of many studies globally, predominantly of focal type, earlier onset among women, and more cases of limb dystonias when compared with more prominent blepharospasm and cervical dystonias in western reports. PMID- 17722046 TI - Complications of therapeutic plasma exchange: a prospective study of 1,727 procedures. AB - The type and number of complications was prospectively examined in 1,727 successive TPE treatments in 174 patients over 66 months at a single center. Most treatments were prescribed for thrombotic thrombocytopenic purpura (TTP; 42%), recurrent focal segmental glomerulosclerosis (FSGS; 22%), or myasthenia gravis (MG; 13%). About 57% of treatments used albumin-saline as the replacement solution and 43% used fresh-frozen plasma (FFP), almost all for TTP. There were 889 complications; 614 treatments (36% of the total) involved a complication. Most complications were minor; there were no deaths. Three treatments (0.2%) were discontinued due to a complication, and 2 (0.1%) required transfer to a higher acuity hospital bed. The most common complications were fever (7.7% of treatments), urticaria (7.4%), and hypocalcemic symptoms (7.3%). 42% of treatments with FFP involved a complication, compared to 30% of treatments using albumin-saline (P < 0.0001). The most common complications with FFP were urticaria (17%) and pruritus (13%); these occurred more commonly than in patients receiving albumin-saline. The most common complications with albumin-saline replacement were hypocalcemic symptoms (8.2%) and mild hypotension (8.1%). Mild and severe hypotension was significantly (P < 0.0001) more common with albumin saline replacement. TPE is associated with a number of minor complications. Complications occur more commonly with FFP replacement compared to albumin-saline replacement. Pruritus and urticaria occur more commonly with FFP, and hypotension occurs more commonly with albumin-saline. PMID- 17722045 TI - Cocaine- and amphetamine-regulated transcript is increased in Huntington disease. AB - Weight loss and anxiety frequently occur in individuals with Huntington's disease (HD) but the underlying mechanisms are not well-understood. Peptides produced in the hypothalamus are involved in regulating energy homeostasis and emotion. Recent data suggest that changes in neuropeptide levels may be reflected in the cerebrospinal fluid (CSF), and could therefore serve as biomarkers for HD. Cocaine- and amphetamine-regulated transcript (CART) is a neuropetide expressed in several brain regions such as the hypothalamus, amygdala, and hippocampus. CART has been shown to increase anxiety and reduce food intake in rodents by as yet unknown mechanisms. Individuals with a CART mutation exhibit increased anxiety. In cross-sectional CSF samples from HD patients (n = 39), we found that levels of CART peptide were significantly increased by 23% compared to control subjects (n = 28). Increased CART levels in HD therefore hold promise as a biomarker as well as a potential pathogenic mediator of symptoms. PMID- 17722047 TI - Continuous infusion of calcium gluconate in 5% albumin is safe and prevents most hypocalcemic reactions during therapeutic plasma exchange. AB - While therapeutic plasma exchanges (TPEs) performed with 5% albumin are considered safe, concerns regarding venous access and hypocalcemic toxicity remain. We reviewed the frequency of complications during TPEs performed with 5% albumin supplemented with calcium gluconate and potassium chloride for a 5 year period in our institution. Eighty-four adult patients (46 males and 38 females) underwent 581 plasma exchanges during the study period. The most common indications were myasthenia gravis (37%), acute inflammatory demyelinating polyradiculoneuropathy (31%), and chronic inflammatory demyelinating polyneuropathy (13%). All procedures used 2.2% ACD-A delivered at a calculated average rate of 0.26 mg/kg/min, which led to a mean dose of citrate per TPE of 2.18 +/- 0.48 g or 27.8 +/- 5.24 mg/kg of body weight. Venous access difficulties occurred in 85 procedures (14.6%), but most TPEs were completed successfully. Hypotension and citrate toxicity were seen in <5% of the TPEs and were mostly reversible. Only 17 exchanges (3%) had to be aborted because of the loss of venous access (n = 9), hypocalcemic toxicity (n = 3), hypotension (n = 2), panic attacks (n = 2), and one atypical reaction due to the interaction with an angiotensin converting enzyme inhibitor. Comparison between pre- and post-TPE potassium levels showed a statistically significant mean decrease of 7%, from 4.1 mequiv/l to 3.8 mequiv/l (P < 0.0001). We attribute the low rate of hypocalcemia to our practice of adding calcium and potassium to the replacement fluid and suggest that this method could become standard of care. PMID- 17722048 TI - Muscle membrane excitability after exercise in thyrotoxic periodic paralysis and thyrotoxicosis without periodic paralysis. AB - We evaluated whether the paralytic attacks in thyrotoxic periodic paralysis (TPP) are primarily due to the abnormal excitability of the muscle membrane caused by a preexisting latent abnormality or to the effects of thyroid hormone. The prolonged exercise (PE) test was used to evaluate muscle membrane excitability in 21 patients with TPP and 11 patients with thyrotoxicosis without paralytic attacks (Tw/oPP) in the hyperthyroid state. The PE tests were compared between the hyperthyroid and euthyroid states in five of the TPP and three of the Tw/oPP patients. Compared to 20 healthy subjects, a significant increase in compound muscle action potential (CMAP) amplitudes immediately after exercise and a significant time-dependent gradual decline in CMAP amplitudes starting from 20 min after exercise were observed in the TPP patients. A significant decline in CMAP amplitudes was also observed in the Tw/oPP patients but only at 50 min after exercise. All of the TPP and Tw/oPP patients had a tendency to improve in the euthyroid state; the PE tests remained abnormal only in the TPP patients. Paralytic attacks in TPP patients are due primarily to a preexisting latent abnormal excitability of the muscle membrane, possibly genetic in origin. PMID- 17722049 TI - The excitatory thalamo-"cortical" projection within the song control system of zebra finches is formed by calbindin-expressing neurons. AB - The learning and production of vocalizations in songbirds are controlled by a system of interconnected brain nuclei organized into a direct vocal motor pathway and an anterior forebrain (pallium-basal ganglia-thalamo-pallial) loop. Here we show that the thalamo-pallial ("thalamo-cortical") projection (from the medial part of the dorsolateral thalamic nucleus to the lateral magnocellular nucleus of the anterior nidopallium--DLM to LMAN) within the anterior forebrain loop is composed of cells positive for the calcium-binding protein calbindin. We show that the vast majority of cells within DLM express calbindin, based both on immunocytochemistry (ICC) for calbindin protein and in situ hybridization for calb mRNA. Using a combination of tract-tracing and ICC we show that the neurons that participate in the DLM-to-LMAN projection are calbindin-positive. We also demonstrate that DLM is devoid of cells expressing mRNA for the GABAergic marker zGAD65. This observation confirms that the calbindin-expressing cells in DLM are not GABAergic, in accordance with previous electrophysiological data indicating that the DLM-to-LMAN projection is excitatory. Furthermore, we use ICC to determine the trajectory of the fibers within the DLM-to-LMAN projection, and to demonstrate a sex difference in calbindin expression levels in the fibers of the DLM-to-LMAN projection. Our findings provide a clear-cut neurochemical signature for a critical projection in the songbird vocal control pathways that enable song learning. PMID- 17722050 TI - Innervation and neurotransmitter localization in the lung of the Nile bichir Polypterus bichir bichir. AB - Anatomical and functional studies of the autonomic innervation in the lung of dipnoan fishes and the bichirs are lacking. The present immunohistochemical studies demonstrated the presence of nerve fibers in the muscle layers of the lung of the bichir, Polypterus bichir bichir, and identified the immunoreactive elements of this innervation. Tyrosine hydroxylase, acetylcholinesterase, and peptide immunoreactivity was detected in the intramural nerve fibers. Extensive innervation was present in the submucosa where adenylatecyclase/activating polypeptide 38, substance P, P(2)X(2), and 5-hydroxytryptamine (5-HT) immunoreactive nerve fibers mainly supplied blood vessels. A collection of monopolar neurons located in the submucosal and the muscular layers of the glottis expressed a variety of various transmitters. These neurons may be homologous to ganglion cells in the branchial and pharyngeal rami of the vagus in fishes. Nerves containing 5-HT and P(2)X(2) receptor immunoreactivity projected to the lung epithelium. Associated with neuroepithelial cells in mucociliated epithelium, were neuronal nitric oxide synthase-immunopositive axons. The physiological function of this innervation is not known. The present study shows that the pattern of autonomic innervation of the bichir lung may by similar in its elements to that in tetrapods. PMID- 17722051 TI - Nitric oxide production in PCD: possible evidence for differential nitric oxide synthase function. AB - Primary cilliary dyskinesia (PCD) is characterized by decreased levels of fractional exhaled nitric oxide (FeNO), thought to reflect low activity of airway inducible nitric oxide synthase (iNOS) levels. Alveolar NO (Calv) concentration and bronchial NO (JNO) flux can be calculated from FeNO measured at multiple exhalation flow rates. We hypothesised that whereas bronchial NO would be reduced in PCD due to reduced iNOS function, alveolar NO would reflect endothelial NOS (eNOS) function and be normal. We recorded the medical history; measured FeNO at multiple flow rates (50, 100, 200, 260 ml/sec); and performed spirometry in 24 children (aged 8-16 years). FeNO50 of the PCD children was significantly lower than normal mean (+/-SD) 8.1 +/- 1.3 ppb versus 12.5 +/- 1.6 ppb, P = 0.033. The mean +/- SD values of PCD (n = 24) and normal (n = 20) subjects were respectively: JNO: 383.5 +/- 307.9 versus 650.1 +/- 489 pl/s, P = 0.033, Calv: 1.60 +/- 0.78 versus 1.60 +/- 0.75 ppb, P = NS. We show that Calv is normal in PCD, demonstrating that there is no generalized disorder of NO handling in this condition. This differs from a previous report. Furthermore, we speculate that these data may provide supportive evidence that variable flow NO measurements can assess the relative activity of iNOS and eNOS. PMID- 17722053 TI - Deadspace estimation from CO2 versus molar mass measurements in infants. AB - BACKGROUND: Estimation of respiratory deadspace is often based on the CO2 expirogram, however presence of the CO2 sensor increases equipment deadspace, which in turn influences breathing pattern and calculation of lung volume. In addition, it is necessary to correct for the delay between the sensor and flow signals. We propose a new method for estimation of effective deadspace using the molar mass (MM) signal from an ultrasonic flowmeter device, which does not require delay correction. We hypothesize that this estimation is correlated with that calculated from the CO2 signal using the Fowler method. METHODS: Breath-by breath CO2, MM and flow measurements were made in a group of 77 term-born healthy infants. Fowler deadspace (Vd,Fowler) was calculated after correcting for the flow-dependent delay in the CO2 signal. Deadspace estimated from the MM signal (Vd,MM) was defined as the volume passing through the flowhead between start of expiration and the 10% rise point in MM. RESULTS: Correlation (r = 0.456, P < 0.0001) was found between Vd,MM and Vd,Fowler averaged over all measurements, with a mean difference of -1.4% (95% CI -4.1 to 1.3%). Vd,MM ranged from 6.6 to 11.4 ml between subjects, while Vd,Fowler ranged from 5.9 to 12.0 ml. Mean intra measurement CV over 5-10 breaths was 7.8 +/- 5.6% for Vd,MM and 7.8 +/- 3.7% for Vd,Fowler. Mean intra-subject CV was 6.0 +/- 4.5% for Vd,MM and 8.3 +/- 5.9% for Vd,Fowler. Correcting for the CO2 signal delay resulted in a 12% difference (P = 0.022) in Vd,Fowler. Vd,MM could be obtained more frequently than Vd,Fowler in infants with CLD, with a high variability. CONCLUSIONS: Use of the MM signal provides a feasible estimate of Fowler deadspace without introducing additional equipment deadspace. The simple calculation without need for delay correction makes individual adjustment for deadspace in FRC measurements possible. This is especially important given the relative large range of deadspace seen in this homogeneous group of infants. PMID- 17722052 TI - Lung inflammation and pulmonary function in infants with meconium aspiration syndrome. AB - OBJECTIVE: To evaluate the relationship between inflammation and pulmonary function, we quantified changes in inflammatory cellular profile, pro inflammatory cytokines, and pulmonary function in intubated neonates with meconium aspiration syndrome (MAS). METHODS: Sixteen term infants were studied. Tracheal aspirate fluids, obtained within the first 6, 24, 48, and 96 hr of life were used for measurements of: (1) cellular profile changes; (2) mRNA and protein levels for pro-inflammatory cytokines, IL-1beta, IL-6, IL-8, and TNF-alpha, using RT-PCR and ELISA. Using the same time points as above, we determined mean airway pressure, oxygenation index (OI), alveolar-arterial oxygen gradient, and arterial/alveolar oxygen ratio. Baseline tidal volume and pulmonary compliance were obtained. RESULTS: Birth weight was 3,820 +/- 656 g, gestational age 39.8 +/ 1.4 weeks. Mean airway pressure and OI significantly decreased from the first 6 96 hr of age (P = 0.01, P = 0.027). Cell counts were elevated in the first 6 hr compared to 96 hr (17.4 x 10(6)/ml vs. 1.5 x 10(6)/ml, P < 0.05). Pro inflammatory cytokines decreased from the first 6-96 hr: IL-1beta (187 vs. 37 pg/ml, P < 0.05); IL-6 (3,469 vs. 150 pg/ml, P < 0.05); IL-8 (16,230 vs. 6,334 pg/ml, P = 0.01). CONCLUSIONS: MAS is associated with an inflammatory response characterized by the presence of elevated cell count and pro-inflammatory cytokines which significantly decreased by 96 hr of life. This decrease in lung inflammation has a positive correlation with corresponding decreases in mean airway pressure and oxygenation index, two parameters associated with improved pulmonary function. PMID- 17722054 TI - Methacholine and adenosine 5'-monophosphate challenges in preschool children with cough-variant and classic asthma. AB - Bronchial challenge with different stimuli provides different information and may be used as an adjunct to understand the pathophysiology of cough variant asthma (CVA) in young children in whom the mechanism of disease is still unresolved. This study was designed to investigate the hypothesis that airway hyperresponsiveness (AHR) to methacholine and adenosine 5'-monophosphate (AMP) is similar in preschool children with CVA and classic asthma. We examined airway response to methacholine and AMP in well-defined 3-6-year-old children with CVA (n = 18), classic persistent asthma (n = 31), and healthy controls (n = 10) by transcutaneous oxygen monitorization. The number of AMP responsive children was significantly lower in the group with CVA (38.9%) than classic persistent asthma (67.7%) (P = 0.049). Mean provocative concentration of AMP causing a 15% fall in transcutaneous oxygen tension (PC15PtcO2 AMP) in children with CVA and classic persistent asthma were 234.58 and 36.35 mg/ml, respectively (P = 0.001). None of the healthy children in the control group responded to AMP. The severity of methacholine responsiveness was found similar in CVA and classic persistent asthma groups (P = 0.738). Although both asthma groups showed a similar pattern in methacholine responsiveness, preschool children with CVA were found to differ from children with classic persistent asthma with regard to response profiles to AMP challenge which may point to different pathophysiologic mechanisms of CVA in the young age group. PMID- 17722055 TI - Evaluation of top, angle, and side cleaned FIB samples for TEM analysis. AB - TEM specimens of a LaAlO(3)/SrTiO(3) multilayer are prepared by FIB with internal lift out. Using a Ga(+1) beam of 5 kV, a final cleaning step yielding top, top angle, side, and bottom-angle cleaning is performed. Different cleaning procedures, which can be easily implemented in a dual beam FIB system, are described and compared; all cleaning types produce thin lamellae, useful for HRTEM and HAADF-STEM work up to atomic resolution. However, the top cleaned lamellae are strongly affected by the curtain effect. Top-angle cleaned specimens show an amorphous layer of around 5 nm at the specimen surfaces, due to damage and redeposition. Furthermore, it is observed that the LaAlO(3) layers are preferentially destroyed and transformed into amorphous material, during the thinning process. PMID- 17722056 TI - Ultrastructural modifications of cell membranes induced by "electroporation" on melanoma xenografts. AB - Electroporation (EP) has been widely employed in the past years as a safe and effective technique to drive drugs and DNA plasmids into target cells both for experimental and therapeutic purposes. Despite the large bulk of literature on this topic, often describing successful outcomes, there is a lack of knowledge about the intimate mechanism(s) controlling this phenomenon. In this paper, we describe a number of ultrastructural alterations in the cellular membranes following the exposure of orthotopic melanomas and red blood cells to trains of biphasic pulses. Specifically, melanoma xenografts grown in nude mice were subject to trains of eight biphasic pulses using an electric field of 1250 or 2450 V/cm, excised after 5 min and processed for electron microscopy. The freeze fracturing analysis of both cell types evidenced defects in the dynamic assembly of lipids and proteins, which generate "areas with rough structure" and intensive clustering of intramembrane proteins. Such modifications could be the hallmarks of lipid and protein alterations, of protein cohesion reduction, and of changes in lipid orientation inside cell membranes, as postulated in several mathematical models applied to electroporation, and warrant further investigations. PMID- 17722057 TI - Imaging FRET standards by steady-state fluorescence and lifetime methods. AB - Imaging fluorescence resonance energy transfer (FRET) between molecules labeled with fluorescent proteins is emerging as a powerful tool to study changes in ions, ligands, and molecular interactions in their physiological cellular environment. Different methods use either steady-state fluorescence properties or lifetime to quantify the FRET rate. In addition, some provide the absolute FRET efficiency whereas others are simply a relative index very much influenced by the actual settings and instrumentation used, which makes the interpretation of a given FRET rate very difficult. The use and exchange of FRET standards in laboratories using these techniques would help to overcome this drawback. We report here the construction and systematic evaluation of FRET standard probes of varying FRET efficiencies. The standards for intramolecular FRET were protein fusions of the cyan and yellow variants of A. victoria green fluorescent protein (ECFP and citrine) joined by short linkers or larger protein spacers, or ECFP tagged with a tetracysteine motif and labeled with the biarsenical fluorochrome, FlAsH. Negative and positive controls of intermolecular FRET were also used. We compared these FRET standards with up to four FRET quantification methods: ratioing of acceptor to donor emission, donor intensity recovery upon acceptor photobleach, sensitized emission after spectral unmixing of raw images, and fluorescence lifetime imaging (FLIM). The latter was obtained with a frequency domain setup able to provide high quality lifetime images in less than a second, and is thus very well suited for live cell studies. The FRET rates or indexes of the standards were in good agreement regardless of the method used. For the CFP tetraCys/FlAsH pair, the rate calculated from CFP quenching was faster than that obtained by FLIM. PMID- 17722059 TI - Age-related changes of NADPH-diaphorase-positive neurons in the rat inferior colliculus and auditory cortex. AB - Nitric oxide (NO) has been implied in age-related changes of the central nervous system (CNS) and the central auditory pathway. The present study was conducted to investigate whether the number of NO-producing cells and their morphometric characteristics in the inferior colliculus (IC) and the auditory cortex (AC) are changed with the increasing age of the subjects. IC and AC sections of adult and senile Wistar rats were studied using the histochemical detection of NADPH diaphorase activity (NADPH-d), a marker for neurons containing nitric oxide synthase (NOS). Our results showed a decreased area of the somas of NADPH-d positive neurons in the dorsal cortex (DC) of the IC and a diffuse loss of NADPH d-positive neurons in the senile IC and primary cortical auditory area (Te1). However, an increased number of NO-producing cells have been shown by other authors in different parts of the ageing auditory pathway and CNS. It seems that age-related changes in NADPH-d-positive cells may follow a region-specific route. These changes may be related to hearing impairments with increasing age. PMID- 17722058 TI - An improved confocal FRAP technique for the measurement of long-term actin dynamics in individual stress fibers. AB - The present study describes an improved fluorescent recovery after photobleaching (FRAP) technique, which has been successfully used to quantify actin dynamics within individual fibers. Chondrocytes were transfected with an eGFP-actin plasmid and cultured on glass coverslips. In cells expressing eGFP-actin, confocal microscopy was used to bleach 3 x 1 microm regions accurately positioned along individual stress fibers. The subsequent fluorescent recovery over a 10-min imaging period was assessed from a series of intensity profiles, positioned along the length of the stress fibers and spanning the bleach region. From these profiles, the normalized fluorescent intensity values were plotted against time. In this way, the technique provided sufficient spatial precision to describe the long-term behavior within individual stress fibers while accounting for the inherent movement. An identical procedure was used to examine FRAP for eGFP-actin within the interfiber region. The FRAP curves for stress fibers were accurately modeled by two phase exponentials which indicated only partial recovery with a mobile fraction of 46%. This suggests that some of the F-actin molecules were in a tightly bound configuration with negligible turnover. The interfiber region exhibited similar two phase exponential FRAP with a mobile fraction of 68%. This partial recovery may be due to the presence, within the interfiber region, of both G-actin and fine F-actin fibers beneath the resolution of the confocal microscope. In conclusion, the present FRAP methodology overcomes many of the limitations of previous studies in order to provide new data describing long-term actin dynamics within individual stress fibers. PMID- 17722060 TI - Inducible cAMP early repressor (ICER)-evoked delayed neuronal death in the organotypic hippocampal culture. AB - Programmed cell death involving gene regulation and de novo protein synthesis is a major component of both normal development and a number of disease conditions. Hence, knowledge of its mechanisms, especially transcription factors, that regulate expression of the genes involved in neurodegenerative disorders is of great importance. cAMP-responsive element-binding protein (CREB) has repeatedly been implicated in the neuronal survival. In the present study we showed that inducible cAMP early repressor (ICER), an endogenous CREB antagonist, is expressed during both excitotoxic and spontaneous neuronal cell death in organotypic hippocampal slice cultures in vitro. Furthermore, overexpression of ICER via an adenoviral vector evoked neuronal cell loss in such cultures. The time course of ICER-dependent cell death was hippocampal subdivision specific, with dentate gyrus neurons dying mostly 3-7 days after the adenovector infection, followed by CA3, where neuronal death peaked after 7 days, and then CA1, where most neuronal death occurred after 7-14 days. These results underscore the usefulness of the organotypic cultures for studies of neurodegeneration and point to neuronal loss having a multifaceted nature in a complex cellular environment. PMID- 17722061 TI - Maternal embryonic leucine zipper kinase is a key regulator of the proliferation of malignant brain tumors, including brain tumor stem cells. AB - Emerging evidence suggests that neural stem cells and brain tumors regulate their proliferation via similar pathways. In a previous study, we demonstrated that maternal embryonic leucine zipper kinase (Melk) is highly expressed in murine neural stem cells and regulates their proliferation. Here we describe how MELK expression is correlated with pathologic grade of brain tumors, and its expression levels are significantly correlated with shorter survival, particularly in younger glioblastoma patients. In normal human astrocytes, MELK is only faintly expressed, and MELK knockdown does not significantly influence their growth, whereas Ras and Akt overexpressing astrocytes have up-regulated MELK expression, and the effect of MELK knockdown is more prominent in these transformed astrocytes. In primary cultures from human glioblastoma and medulloblastoma, MELK knockdown by siRNA results in inhibition of the proliferation and survival of these tumors. Furthermore, we show that MELK siRNA dramatically inhibits proliferation and, to some extent, survival of stem cells isolated from glioblastoma in vitro. These results demonstrate a critical role for MELK in the proliferation of brain tumors, including their stem cells, and suggest that MELK may be a compelling molecular target for treatment of high grade brain tumors. PMID- 17722062 TI - The myelin-associated glycoprotein inhibitor BENZ induces outgrowth and survival of rat dorsal root ganglion cell cultures. AB - The novel myelin-associated glycoprotein (MAG) inhibitor BENZ binds to the N acetylneuraminic acid (Neu5Ac) portion of the N-terminal Ig-like domain of MAG. Treatment of rat dorsal root ganglion (DRG) cell cultures with BENZ-induced outgrowth of neurofilament 200-positive neurites improved survival of neurons and increased the number of GFAP-positive cells, as determined by fluorescence and confocal laser microscopy and by Western immunoblotting. Furthermore, treatment of DRG cell cultures with BENZ repressed gene and protein expression of the small GTPase RhoA but induced expression of Rho GTP-activating proteins 5 and 24, likely to counteract protein kinase A activity. Specifically, expression of inhibitors of neurite outgrowth, for example, Rock2 and PAK4, was repressed, but cofilin 1, a promoter of axonal growth, was induced. We propose that the MAG inhibitor BENZ abrogates the RhoA-ROCK-cofilin pathway to promote neurite outgrowth. Our findings require confirmation by in vivo animal studies. PMID- 17722063 TI - Structure, properties, and functions of the human small heat-shock protein HSP22 (HspB8, H11, E2IG1): a critical review. AB - The recently described human HSP22 belongs to the superfamily of small heat-shock proteins containing a conservative alpha-crystallin domain. HSP22 seems to be involved in regulation of cell proliferation, cardiac hypertrophy, apoptosis, and carcinogenesis, and expression of point mutants of HSP22 correlates with development of different neuromuscular diseases. Therefore, an investigation of the structure and properties of HSP22 is desirable for understanding its multiple functions. HSP22 seems to belong to the group of so-called intrinsically disordered proteins and possesses a highly flexible structure. HSP22 tends to form small-molecular-mass oligomers and interacts with biological membranes and many different proteins, among them glycolytic enzymes and different protein kinases. HSP22 possesses chaperonelike activity and prevents aggregation of denatured proteins both in vitro and in vivo. Depending on the cell type and its expression, HSP22 might have either pro- or anti-apoptotic effects. Chaperonelike activity seems to be important for antiapoptotic effects, whereas interaction with and regulation of certain protein kinases might be important for the proapoptotic effects of HSP22. Expression of K141N or K141E mutants of HSP22 correlates with development of distal hereditary motor neuropathy and/or Charcot Marie-Tooth disease. These mutations destabilize the structure of HSP22, affect its interaction with other small heat-shock proteins, and decrease its chaperonelike activity. HSP22 decreases or prevents aggregation of Huntingtin fragments and amyloid-beta peptide 1-40 of the Dutch type. Thus, HSP22 seems to play an important role in the nervous system, and further investigations are needed to understand the molecular mechanisms of its functioning. PMID- 17722064 TI - Nuclear magnetic resonance studies of energy metabolism and glutamine shunt in hepatic encephalopathy and hyperammonemia. AB - Hepatic encephalopathy (HE) in both acute and chronic liver failure is more likely a reversible functional disease rather than an irreversible pathological lesion of brain cells. Metabolic alterations underlie many of the mechanisms leading to HE. This paper summarizes in vivo and ex vivo (1)H-, (13)C-, and (15)N nuclear magnetic resonance (NMR) spectroscopy data on patients and experimental models of HE. In vivo NMR spectroscopy provides a unique opportunity to study metabolic changes noninvasively in the brain in vivo, and to quantify various metabolites in localized brain areas, and ex vivo NMR permits the high-resolution measurement of metabolites and the identification of different metabolic pathways. In vivo and ex vivo (1)H-NMR investigations consistently reveal severalfold increases in brain glutamine and concomitant decreases in myo inositol, an important osmolyte in astrocytes. An osmotic disturbance in these cells has long been suggested to be responsible for astrocyte swelling and brain edema. However, ex vivo (13)C-NMR studies have challenged the convention that glutamine accumulation is the major cause of brain edema in acute HE. They rather indicate a limited anaplerotic flux and capacity of astrocytes to detoxify ammonia by glutamine synthesis and emphasize distortions of energy and neurotransmitter metabolism. However, recent (15)N-NMR investigations have demonstrated that glutamine fluxes between neurons and astrocytes are affected by ammonia. Further NMR studies may provide novel insights into the relationship between brain edema and/or astrocyte pathology and changes in inter- and intracellular glutamine homeostasis, which may secondarily alter brain energy metabolism. PMID- 17722065 TI - Expression of an acyl-CoA synthetase, lipidosin, in astrocytes of the murine brain and its up-regulation during remyelination following cuprizone-induced demyelination. AB - Lipidosin is an 80-kDa protein with long-chain acyl-CoA synthetase activity expressed in the brain, adrenal gland, testis, and ovary, which are selectively damaged in X-linked adrenoleukodystrophy (X-ALD). Western blot analysis of the cerebrum and cerebellum revealed a gradual increase in the expression of lipidosin postnatally. Light microscopic immunohistochemistry using a panel of specific monoclonal antibodies showed that the lipidosin-immunopositive cells were ubiquitously distributed in the brain and were denser in the gray matter than in the white matter. Lipidosin immunoreactivity was colocalized with GFAP immunoreactivity but not with ubiquitin C-terminal hydrolase 1 (= PGP9.5) immunoreactivity, a neuronal marker, and lipidosin-producing cells detected by an antisense probe specific for lipidosin mRNA were also GFAP immunopositive. These data together with Western blot analysis of primary cultured astrocytes indicate that lipidosin is expressed in astrocytes. Immunoelectron microscopic analysis revealed that lipidosin immunoreactivity was widely distributed from perivascular endfeet to perisynaptic processes without being limited to peroxisomes. Lipidosin immunoreactivity was greatly increased in astrocytes in the area of remyelination following experimental demyelination induced by the administration of cuprizone to mice. These data suggest that lipidosin was involved in fatty acid metabolism during reconstruction of the myelin sheath. PMID- 17722067 TI - Axogenic effect of estrogen in male rat hypothalamic neurons involves Ca(2+), protein kinase C, and extracellular signal-regulated kinase signaling. AB - 17-beta-Estradiol (E2) stimulates the growth of axons in male-derived hypothalamic neurons in vitro. This effect is not exerted through the classical intracellular estrogen receptor (ER) but depends on a membrane mechanism involving TrkB. In the present study, we investigate the intracellular signaling cascade that mediates the axogenic effect of E2. Treatment with an intracellular Ca(2+) chelator, a Ca(2+)-dependent protein kinase C (PKC) inhibitor, or two specific inhibitors of extracellular signal-regulated kinases (ERK) mitogen activated protein kinases (MAPK) completely inhibited the E2-induced axogenesis. E2 and the membrane-impermeant construct E2BSA rapidly induced phosphorylation of ERK, which was blocked by the specific inhibitor of the ERK pathway UO126 but not by the ER antagonist ICI 182,780. Decrease of intracellular free Ca(2+) or disruption of PKC activation by Ro 32-0432 attenuated ERK activation, indicating the confluence of signals in the MAPK pathway. Subcellular analysis of ERK demonstrated that the phospho-ERK signal is augmented in the nucleus after 15 min of E2 stimulation. We have also shown that E2 increased phosphorylation of CREB via ERK signaling. In summary, this study demonstrates that E2, probably via a membrane-associated receptor, induces axonal growth by activating CREB phosphorylation through ERK signaling by a mechanism involving Ca(2+) and PKC activation. PMID- 17722068 TI - Vertebrate rod photoreceptors express both BK and IK calcium-activated potassium channels, but only BK channels are involved in receptor potential regulation. AB - In salamander rods, Ca(2+)-activated K(+) current (I(KCa)) provides an effective "clamp" of the dark membrane potential to its normal resting level. By a combination of electrophysiological, pharmacological, and immunohistochemical approaches, we show that salamander rods functionally express large-conductance Ca(2+)- and voltage-dependent potassium (BK) channel and intermediate-conductance Ca(2+)-dependent potassium (IK) channel, but not small-conductance Ca(2+) dependent potassium channel (SK) subtypes. Application of 100 nM iberiotoxin and 100 nM clotrimazole reduced net I(KCa) to 36% and 63%, respectively, whereas the current was unaffected by application of 1 microM apamin. Consistently, anti- SK1, -SK2, and -SK3 antibodies were unable to stain rod photoreceptors, whereas both anti-BK and -SK4/ IK1 antibodies heavily stained the ellipsoid region of the inner segments of the rods. Moreover, by using current-clamp experiments, it was clearly seen that the strong clamping effect of the total I(KCa) was lost when IbTx, but not CLTZ, was applied to the bath. This behavior strongly suggests that of BK and IK channels, only the former are responsible for the clamping effect on the photoreceptor membrane potential. PMID- 17722066 TI - Bone morphogenetic proteins 4, 6, and 7 are up-regulated in mouse spinal cord during experimental autoimmune encephalomyelitis. AB - Although spontaneous remyelination occurs in multiple sclerosis (MS), the extent of myelin repair is often inadequate to restore normal function. Oligodendrocyte precursors remaining in nonremyelinating MS plaques may be restricted by an inhibitory signal. Bone morphogenetic proteins (BMPs) have been implicated as repressors of oligodendrocyte development and inducers of astrogliogenesis. We hypothesized that BMPs are up-regulated in MS lesions and play a role in demyelination and astrogliosis. We examined expression of BMPs in an animal model of MS, chronic experimental autoimmune encephalomyelitis (EAE) induced by the myelin oligodendrocyte glycoprotein (MOG) peptide in C57BL/6 mice. By 14 days postimmunization, compared to those of control mice, the lumbar spinal cords of MOG-peptide EAE mice demonstrated prominent astrogliosis, infiltration of inflammatory cells, and disrupted expression of myelin proteins. Quantitative RT PCR showed that expression of BMP4, BMP6, and BMP7 mRNA increased 2- to 4-fold in the lumbar spinal cords of animals with symptomatic EAE versus in vehicle-treated and untreated controls on days 14, 21, and 42 postimmunization. BMP2 mRNA expression was not altered. BMP4 mRNA was much more abundant in the spinal cords of all animals than was mRNA encoding BMP2, BMP6, and BMP7. Immunoblot analysis confirmed the increased expression of BMP4 in the EAE animals. Immunohistochemistry revealed increased BMP4 immunoreactivity in areas of inflammation in MOG-peptide EAE animals. BMP4 labeling was mostly limited to macrophages but was sometimes associated with astrocytes and oligodendrocytes. These results indicate that members of the BMP family are differentially expressed in adult spinal cord and are up-regulated during EAE. (c) 2007 Wiley Liss, Inc. PMID- 17722069 TI - ERK1 plays a critical protective role against N-methyl-D-aspartate-induced retinal injury. AB - Excitotoxicity has been implicated in several ischemic diseases of the retina, including retinal vessel occlusion and diabetic retinopathy. Glutamate signaling mediated through the N-methyl-D-aspartate (NMDA) receptor contributes to ischemic cell death. The NMDA receptor antagonists MK-801 and memantine have substantial neuroprotective effects in experimental retinal disease models, but the mechanisms by which NMDA receptor activity leads to cell death is not clear. Here we describe a previously unknown role for retinal glial cells in NMDA-induced retinal injury that involves the activation of ERK1/2. Within 1 hr after injecting NMDA intravitreally, activation of ERK1/2 and c-Fos induction were observed in retinal Muller cells. The roles of activated ERK1/2 in neuronal damage were examined using ERK1 gene deficient mice (homozygous ERK1(-/-) mice). NMDA-induced ERK1/2 activation in retina was significantly suppressed in ERK1(-/ ) mice, and these mice had significantly higher numbers of TUNEL-positive retinal cells than wild-type mice 24 hr after NMDA injection. These data suggest that, during NMDA injury, Muller cells are activated and play a protective role against NMDA-induced retinal cell death. ERK1 appears to play a major role in this process. These new findings on retinal glial cell response during NMDA injury offer an important new therapeutic target for preventing many retinal disorders associated with excitotoxicity. PMID- 17722070 TI - 5-hydroxyoxindole, an indole metabolite, is present at high concentrations in brain. AB - 5-Hydroxyoxindole has been identified as a urinary metabolite of indole, which is produced from tryptophane via the tryptophanase activity of gut bacteria. We have demonstrated recently that 5-hydroxyoxindole is an endogenous compound in blood and tissues of mammals, including humans. To date, 5-hydroxyoxindole's role is unknown. The aim of this study was to compare 5-hydroxyoxindole levels in plasma and cerebrospinal fluid (CSF) during day-night and seasonal changes, as a common approach to pilot physiological characterization of any compound. Simultaneous blood and CSF sampling was performed in the ewe, because its size allows collection in quantities suitable for 5-hydroxyoxindole assay (HPLC-ED) in awake animals, without obvious physiological or behavioral disturbance. 5 Hydroxyoxindole concentration was quite stable in plasma (2-6 nM range), whereas, in CSF, it displayed marked day-night and photoperiodic variations (4-116 nM range). 5-Hydroxyoxindole levels in CSF were twofold higher at night than during the day and at least one order of magnitude higher during the long compared with the short photoperiod. These day/night and photoperiodic variations persisted after pinealectomy, indicating that 5-hydroxyoxindole rhythms in CSF are independent of melatonin formation. In conclusion, high levels of 5 hydroxyoxindole in the CSF during long photoperiod and its daily modulation suggest physiological involvement of 5-hydroxyoxindole in rhythmic adjustments in the brain, independently of the pineal gland. PMID- 17722071 TI - Multifunction of myricetin on A beta: neuroprotection via a conformational change of A beta and reduction of A beta via the interference of secretases. AB - Myricetin (3,3',4',5,5',7-hexahydroxyflavone) is classified as a flavonoid with strong antioxidant effects. Oxidative stress plays a key role in various neurological diseases such as ischemia and Alzheimer's disease (AD). To elucidate whether myricetin could counter the progress of AD, we examined the effects of myricetin on neurotoxicity induced by beta-amyloid (A beta), a component of senile plaques in the AD brain. We found that cultured rat primary cortical neurons treated for 48 hr with A beta1-42 (1 microM) induced significant neuronal injury. Conformationally altered A beta1-42 caused apoptotic changes, such as nuclear fragmentation, as shown by DAPI staining. Pre- and simultaneous administration of myricetin and A beta1-42 reduced A beta neurotoxicity in a concentration-dependent manner. By using circular dichroism spectroscopy and a thioflavin T binding assay, we show that myricetin (10 microM, 48 hr) prevented structural changes in A beta1-42 from a random coil to a beta-sheet-rich structure. A beta1-42-induced apoptotic changes and caspase-3 activation were reduced by myricetin treatment. Furthermore, we determined that administration of myricetin significantly decreased A beta1-40 and A beta1-42 levels in culture media. These effects were based on two mechanisms: the activation and up regulation of alpha-secretase (ADAM10) protein levels as indicated by fluorescence resonance energy transfer (FRET) assay and immunoblot analysis and the direct binding and inhibition of beta-secretase (BACE-1) indicated by cell free FRET assays. Evidently, myricetin has multiple functions to counter the progress of AD by the reduction of A beta production and the detoxification of A beta through a structural change. PMID- 17722072 TI - Self-reported health-related quality of life in adults with chronic immune thrombocytopenic purpura. AB - Adult chronic immune thrombocytopenic purpura (ITP) is a disorder manifested by varying degrees of purpura and mucosal bleeding, rarely including intracranial hemorrhage. Therapy is aimed at increasing the patient's platelet count to safe levels and includes a wide variety of treatments. While the diagnosis, treatment, and prognosis of chronic ITP have been extensively discussed, the effect of ITP and its treatment on patient quality of life has not been evaluated in adults. In this study, the Short-Form 36 questionnaire was used to evaluate the health related quality of life (HRQOL) of 73 adult ITP patients compared with that of the general U.S. population and of patients with six other relatively common chronic disorders. This study shows that the HRQOL of adult patients with ITP is significantly worse than that of the general U.S. population. It is also worse than that of patients with hypertension, arthritis, or cancer; similar to that of patients with diabetes; but better than that of patients with congestive heart failure or a missing or paralyzed limb. Future studies need to address the effects of treatment not only on the platelet count and bleeding but also on HRQOL. PMID- 17722073 TI - G-CSF-mobilized haploidentical peripheral blood stem cell transplantation in children with poor prognostic nonmalignant disorders. AB - Haploidentical hematopoietic stem cell transplantation (HSCT) is currently one of the alternative curative treatment options for some nonmalignant but also for malignant diseases. However, concerns regarding its safety cause delays in time and a successful outcome. Between 2000 and 2005, twenty-one children with poor prognostic nonmalignant disorders, 13 boys and 8 girls, with a median age of 12 months, underwent 28 haploidentical peripheral HSCT. Immunomagnetic bead depletion device (CliniMACS) was used for indirect T-cell depletion. Indications for transplant were severe combined immunodeficiency (n=16), osteopetrosis (n=2), MDS (n=1), amegakaryocytic thrombocytopenia (n=1), and aplastic anemia (n=1). Five patients (24%) had lung infection at the time of transplantation. The patients received a median of 25.67 x 10(6) G-CSF-mobilized peripheral CD34(+) progenitor cells and a median of 4.19 x 10(4) T-lymphocytes per kilogram of body weight with a T-cell depletion rate of median 4.59 logs. The rate of total engraftment was 66.6%. Median times for leukocyte and platelet engraftment were 14 and 16 days, respectively. The 6-year projected survival was 32% for all patients and 29.76% for patients with severe combined immunodeficiency (SCID). The rates of transplant-related mortality, graft failure, and severe GvHD were 14.2, 33.4%, and 8.3%, respectively. Infection was the main cause of death. The poor outcome may be explained with the poor prognostic factors of our patients such as the type of SCID in most cases (T-B- SCID), the median age over 6 months and the presence of lung infection in some children at the time of transplantation. PMID- 17722074 TI - Pharmacogenetics of morphine: Potential implications in sickle cell disease. AB - Morphine is frequently used to treat painful episodes associated with sickle cell disease (SCD) but may fail to provide adequate analgesia in many patients. This concise review focuses on unique disease related changes in physiologic variables associated with SCD that impacts pharmacokinetics and pharmacodynamics of morphine and may contribute to the variability in analgesia. Emerging evidence suggests that the allelic variants in the genes involving the opioid (UGT2B7, OPRM1, and ABCB1 genes) and nonopioid system (COMT gene) can alter the efficacy of morphine. PMID- 17722075 TI - Heparin-induced skin necrosis associated with thrombocytopenia and acquired protein C and protein S deficiency. AB - We have described a patient with colon cancer and liver metastases who developed heparin-induced thrombocytopenia and skin necrosis. We believe that the skin necrosis caused by the heparin/platelet factor 4 antibody was exacerbated by the acquired protein C and protein S deficiency. After the heparin was discontinued and infection treated, the skin necrosis and thrombocytopenia resolved. This case illustrates the fact that, in patients with heparin-induced skin necrosis, a search must be undertaken for an underlying pro-thrombotic state, which may precipitate the microthrombosis responsible for skin necrosis. We could not find any previous case reports of heparin-induced skin necrosis associated with isolated protein C deficiency, or combined protein C and protein S deficiency. PMID- 17722076 TI - Fibrinogen deficiency, but not plasminogen deficiency, increases mortality synergistically in combination with sickle hemoglobin SAD in transgenic mice. AB - Patients with sickle cell disease exhibit both acute and chronic activation of the coagulation and fibrinolytic systems. To test the relationship between sickle cell pathology and activation of the hemostatic system, mice with targeted deletions of plasminogen (Plg) or fibrinogen (Fib) were crossed with transgenic mice expressing Hb SAD [beta(6Glu-Val) (HbS), beta(23Val-Ile) (HbAntilles), and beta(121Glu-Gln) (HbD-Punjab)]. Fibrinogen deficiency dramatically reduced the survival of mice with Hb SAD to a much greater degree than mice with normal hemoglobin. The combination of Hb SAD and fibrinogen deficiency had a greater effect on mortality than that obtained by adding the mortality risks of each defect alone. The deleterious effect of the combination of Hb SAD and fibrinogen deficiency on mortality was accelerated by hypoxia. The excess mortality associated with plasminogen deficiency was identical in SAD and control mice. The adverse effect of fibrinogen deficiency on mortality in SAD mice is not consistent with the simple hypothesis that fibrin deposition is uniformly deleterious in the context of vaso-occlusive sickle cell disease. Rather, our findings suggest that the contribution of fibrinogen to tissue repair may in some contexts limit sickle cell disease pathophysiology. PMID- 17722077 TI - Immunotherapy in mantle cell lymphoma: anti-CD20-based therapy and beyond. AB - Mantle cell lymphoma (MCL), an aggressive non-Hodgkin's lymphoma characterized by t(11; 14)(q13; q32) chromosomal translocation and overexpression of cyclin D1, has the worst prognosis among all lymphomas. Recent advances in biology, genetics, and immunology have supported the development of immunotherapy in MCL. Rituximab monotherapy in MCL has limited activity. It is more effective when used in combination with chemotherapy such as R-CHOP, R-hyperCVAD/MTX-Ara-C, or R-FCM as front-line or salvage therapy for mantle cell lymphoma. Maintenance with Rituximab was shown to prolong response duration. Although most results have suggested that combining autologous stem cell transplantation with Rituximab may lead to durable remission, the sample size was not sufficient to declare survival benefit. Anti-CD20 radioimmunoconjugates (RICs) (90)Yttrium-ibritumomab tiuxetan and (131)Iodine-tositumomab have been used in mantle cell lymphoma even when patients are relatively resistant to Rituximab-based therapy. Allogeneic stem cell transplantation is a treatment modality in advanced or relapsed MCL, particularly using reduced-intensity conditioning. MCL may have high response rates and sustained remissions after donor lymphocyte infusion. Dendritic cells (DCs) fused with MCL cells for immunostimulation have preliminarily shown anti lymphoma effects as well. Idiotype vaccination in MCL patients following Rituximab-containing chemotherapy induced tumor-specific T-cell immunity in the absence of B cells. Other immunotherapy, such as the combination of thalidomide with Rituximab, has shown substantial antitumor activity. A Phase I/II study is ongoing to determine the maximum tolerated dose (MTD) and the efficacy of lenalidomide in combination with Rituximab for relapsed/refractory MCL. This review summarizes the latest and exciting advances in MCL. PMID- 17722078 TI - Splenectomy for immune thrombocytopenic purpura: surgery for the 21st century. AB - Although immune thrombocytopenic purpura (ITP) is the most common autoimmune hematological disorder, there is still controversy regarding the optimal management of this condition. Medical therapy may cure a proportion of patients with ITP but there are still a significant number of these individuals who are at risk for bleeding events. Surgery has become the least popular therapeutic option for ITP as other medical therapies have become available that attempt to avoid splenectomy and its morbidity. However, the clinical response to these therapies has not been overwhelming based on the fairly small number of trials conducted to date. With current minimally invasive surgical techniques, splenectomy should be again regarded as a viable therapeutic option in patients with ITP. The laparoscopic approach avoids much of the morbidity and complications seen with the conventional open surgical approach and studies have demonstrated similar, if not better, outcomes. In addition, the risk of infection following splenectomy is not as high as may be suspected, particularly with current vaccination regiments. It should be a priority for both the hematology and medical community to advocate for clinical trials to rationally study alternatives to splenectomy. In the interim, laparoscopic splenectomy should be considered as an additional front line therapeutic option in ITP patients. PMID- 17722079 TI - What is the potential for overdiagnosis of heparin-induced thrombocytopenia? AB - Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating antibodies that recognize platelet factor 4//heparin (PF4/H) complexes. According to the "iceberg model," only a subset of anti-PF4/heparin antibodies of IgG class evincing strong platelet-activating properties cause clinical HIT. Since many centers rely predominantly on an anti-PF4/polyanion enzyme-immunoassay (EIA) to diagnose HIT, we estimated the potential for overdiagnosis when only this single test is available. We examined a database of 100 patients in whom the probability of HIT had been estimated using a clinical scoring system (4Ts), and where patients underwent systematic testing for HIT antibodies using three assays: the platelet serotonin release assay (SRA), an "in-house" EIA that detects IgG anti PF4/heparin antibodies (EIA-IgG), and a commercial EIA that detects anti PF4/polyanion antibodies of all three immunoglobulin classes (EIA-GTI). Whereas 16 of 100 patients fulfilled a "classic" definition of HIT (intermediate/high probability plus strong platelet-activating anti-PF4/heparin IgG antibodies), an additional 16 patients fulfilled a "liberal" definition in which any investigated patient (irrespective of the pretest probability) who had a positive EIA-GTI was considered to have HIT. The clinical features of these 16 additional patients- including generally weak antibodies and low risk for thrombosis--suggest underlying non-HIT explanations for thrombocytopenia. Patients with a positive SRA generally corresponded to those with intermediate or high pretest probability of HIT who also had strong EIA-GTI reactivity (>1.20 OD units). We conclude there is the potential to overdiagnose HIT by approximately 100% if any positive EIA is considered to "confirm" the diagnosis of HIT irrespective of the clinical scenario. PMID- 17722080 TI - Somatosensory nuclei of the manatee brainstem and thalamus. AB - Florida manatees have an extensive, well-developed system of vibrissae distributed over their entire bodies and especially concentrated on the face. Although behavioral and anatomical assessments support the manatee's reliance on somatosensation, a systematic analysis of the manatee thalamus and brainstem areas dedicated to tactile input has never been completed. Using histochemical and histological techniques (including stains for myelin, Nissl, cytochrome oxidase, and acetylcholinesterase), we characterized the relative size, extent, and specializations of somatosensory regions of the brainstem and thalamus. The principal somatosensory regions of the brainstem (trigeminal, cuneate, gracile, and Bischoff's nucleus) and the thalamus (ventroposterior nucleus) were disproportionately large relative to nuclei dedicated to other sensory modalities, providing neuroanatomical evidence that supports the manatee's reliance on somatosensation. In fact, areas of the thalamus related to somatosensation (the ventroposterior and posterior nuclei) and audition (the medial geniculate nucleus) appeared to displace the lateral geniculate nucleus dedicated to the subordinate visual modality. Furthermore, it is noteworthy that, although the manatee cortex contains Rindenkerne (barrel-like cortical nuclei located in layer VI), no corresponding cell clusters were located in the brainstem ("barrelettes") or thalamus ("barreloids"). PMID- 17722081 TI - Treatment of halogenated organic compounds and monitoring of microbial dynamics in up-flow fixed bed reactors under sequentially alternating pollutant scenarios. AB - Two up-flow fixed bed reactors (UFBR) were operated for 8 months treating a model synthetic wastewater containing 2-fluorobenzoate (2-FB) and dichloromethane (DCM). The stability of the reactors under dynamic conditions, that is, sequentially alternating pollutants (SAP), shock loads, and starvation periods was assessed. Two support materials were used: expanded clay (EC) that does not adsorb 2-FB or DCM, and granular-activated carbon (GAC) that adsorbs 180 mg g(-1) of 2-FB and 390 mg g(-1) of DCM. The reactors were inoculated with a 2-FB degrading strain (FB2) and a DCM degrader (TM1). 2-FB was fed at organic loads ranging from 0 to 800 mg L(-1) d(-1), while DCM was fed at 0-250 mg L(-1) d(-1). 2-FB or DCM were never detected at the outlet of the GAC reactor, while in the EC reactor outlet small amounts were observed. Nevertheless, the highest biological elimination capacity was observed in the EC reactor (over 700 mg L(-1) d(-1) of 2 FB). DGGE analysis revealed a fairly stable bacterial community with the largest shifts occurring during starvation periods and changes in feed composition. Several bacterial strains isolated from the reactors showed capacity for 2-FB degradation, while only strain TM1 degraded DCM. PMID- 17722082 TI - Influences of dopaminergic treatment on motor cortex in Parkinson disease: a MRI/MRS study. AB - The objective of this study was to investigate neurochemical and metabolic changes in the motor cortex in a group of de novo Parkinson's disease (PD) patients before and after 6 mo treatment with the dopamine agonist pergolide. Proton magnetic resonance spectroscopy (1H-MRS) has been used to study striatal and cortical metabolism in PD and other parkinsonisms. So far, no studies evaluating possible brain metabolic changes in PD patients before and after dopaminergic therapy have been reported. De novo PD patients (11) and controls (11) underwent clinical evaluation (UPDRS-III motor evaluation) and a first single-voxel 1H-MRS of the motor cortex. 1H-MRS studies were performed using the PROBE-SV System implemented on a 1.5 Tesla Scanner (GE Medical System, Milwaukee, WI). Pergolide was administered up to a dose of 1 mg t.i.d. After 6 mo follow-up, all patients were clinically evaluated and a second single-voxel 1H-MRS was performed. Lower values of Cho/Cr and NAA/Cr ratios were observed in the motor cortex of PD patients compared with controls (P < 0.02 and P < 0.01, respectively). After 6 mo therapy with pergolide (1 mg t.i.d), PD patients showed an improvement in motor performances (P < 0.05) and an increase in Cho/Cr ratios in the motor cortex at the second 1H-MRS evaluation (P < 0.05) was reported. In conclusion, cortical NAA/Cr and Cho/Cr ratios may be impaired in de novo PD. Dopaminergic therapy capable of improving motor function may restore the Cho/Cr ratio in the motor cortex. PMID- 17722083 TI - Stability and hydrolysis kinetics of spirosuccinimide type inhibitors of aldose reductase in aqueous solution and retardation of their hydrolysis by the target enzyme. AB - The stability and the hydrolysis kinetics of spirosuccinimide type aldose reductase (AR) inhibitors, SX-3030 (racemate) and its optical enantiomers (R- and S-isomers), were investigated in aqueous solution. The hydrolysis followed pseudo first-order kinetics and showed significant pH dependence. Maximum solution stability was observed below pH 2.4, whereas the hydrolysis was gradually catalyzed by hydroxide ion at neutral to alkaline pH while the compounds exhibiting moderate pH-independent stability at acidic to neutral conditions (pH 4-7) to enable oral administration. A pK of 3.7 was obtained from the pH-rate profile, but this kinetically derived pK is approximately 2 pH units below the pK of the parent compounds, suggesting the presence of an acidic intermediate involved in the hydrolysis process. These findings, together with structural analysis, support the notion that the hydrolysis would proceed via nucleophilic attack of a water molecule or hydroxide ion on the scissile carbonyl bond of the succinimide ring to form a succinamic acid intermediate that has a beta-keto acid structure, followed by decarboxylation to give a racemized succinimide ring opened product. On the other hand, the interconversion of the R- and S-isomers did not occur during hydrolysis; however, the hydrolysis of the R-isomer was markedly suppressed by the target enzyme AR whereas that of the S-isomer was not, indicating a high degree of complementarity of interacting surfaces between the R isomer and the enzyme. The results in the present study could provide useful clues for facilitating the appropriate stabilization strategies as well as for evaluating the pharmacological effects on target tissues in vivo, and suggested that the R-isomer may be a suitable candidate as AR inhibitor. PMID- 17722084 TI - Complexation and chiral drug recognition of an amphiphilic phenothiazine derivative with beta-cyclodextrin. AB - Promethazine hydrochloride (PTZ) is an amphiphilic drug derived from the phenothiazine structure that possesses a charged aliphatic chain with a chiral carbon. In the presence of beta-cyclodextrin (beta-CD), this drug undergoes significant changes of its photophysical properties in aqueous solution. Fluorescence spectroscopy measurements show the formation of a 1:1 stoichiometry complex with quantum yield lower than that of the pure PTZ, and two fluorescence lifetimes, which can be assigned to the free and complexed forms of the drug. In addition, (1)H NMR spectra, and 2D rotating-frame Overhauser enhancement spectroscopy (ROESY) were used to characterize the drug and the complex, and to determine the effects of the complexation on the aggregation. For the drug binary system, a noncooperative association process is observed, and in the presence of macrocycle, the chemical shifts reveal a chiral resolution of the drug enantiomers, with different stability constants of the complexes. beta-CD modifies the aggregation of PTZ in an extension that confirms the formation of a 1:1 complex. ROE enhancements and molecular modeling strategies show the most likely structure of the complex in solution, in which one of the phenyl rings is buried into the CD cavity, with a slight inclusion of the aliphatic part. PMID- 17722085 TI - Engineering biodegradable polyester particles with specific drug targeting and drug release properties. AB - Poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) microspheres and nanoparticles remain the focus of intensive research effort directed to the controlled release and in vivo localization of drugs. In recent years engineering approaches have been devised to create novel micro- and nano-particles which provide greater control over the drug release profile and present opportunities for drug targeting at the tissue and cellular levels. This has been possible with better understanding and manipulation of the fabrication and degradation processes, particularly emulsion-solvent extraction, and conjugation of polyesters with ligands or other polymers before or after particle formation. As a result, particle surface and internal porosity have been designed to meet criteria-facilitating passive targeting (e.g., for pulmonary delivery), modification of the drug release profile (e.g., attenuation of the burst release) and active targeting via ligand binding to specific cell receptors. It is now possible to envisage adventurous applications for polyester microparticles beyond their inherent role as biodegradable, controlled drug delivery vehicles. These may include drug delivery vehicles for the treatment of cerebral disease and tumor targeting, and co-delivery of drugs in a pulsatile and/or time-delayed fashion. PMID- 17722086 TI - The impact of drying method and formulation on the physical properties and stability of methionyl human growth hormone in the amorphous solid state. AB - The objective of this work was to investigate the impact of drying method and formulation on the physical stability (aggregation) and selected important physical properties of dried methionyl human growth hormone (Met-hGH) formulations. Solutions of Met-hGH with different stabilizers were dried by different methods (freeze drying, spray drying, and film drying), with and without surfactant. Properties of the dried powders included powder morphology, specific surface area (SSA), protein surface coverage, thermal analysis, and protein secondary structure. Storage stability of Met-hGH in different formulations was also studied at 50 degrees C and at 60 degrees C for 3 months. The dried powders displayed different morphologies, depending mainly on the method of drying and on the presence or absence of surfactant. Film dried powders had the lowest SSA (approximately 0.03 m(2)/g) and the lowest total protein surface accumulation (approximately 0.003%). Surfactant caused a reduction in the SSA of both spray dried and freeze dried powders. Spray dried powders showed greater protein surface coverage and SSA relative to the same formulations dried by other means. Greater in-process perturbations of protein secondary structure were observed with polymer excipients. Formulation impacted physical stability. In general, low molecular weight stabilizers provided better stability. For example, the aggregation rate at 50 degrees C of Met-hGH in a freeze dried trehalose-based formulation was approximately four times smaller than the corresponding Ficoll-70-based formulation. Drying method also influenced physical stability. In general, the film dried preparations studied showed superior stability to preparations dried by other methods, especially those formulations employing low molecular weight stabilizers. PMID- 17722088 TI - Base excision repair pathway is involved in the repair of lesions generated by flavonoid-enriched fractions of pepper tree (Schinus terebinthifolius, Raddi) stem bark. AB - Cell-free and bacterial assays indicate that flavonoid-enriched fractions and the flavonoids of pepper tree stem bark from Schinus terebinthifolius Raddi have genotoxic rather than antigenotoxic properties. In the present report, we have examined the ability of flavonoid-enriched fractions to damage plasmid DNA and the repair pathways involved in the recognition of these DNA lesions. High concentrations of two flavonoid-enriched fractions were able to break phosphodiester bonds in DNA. In addition, studies using bacterial strains deficient in nucleotide excision repair and base excision repair (BER) enzymes indicated that the flavonoid-enriched fractions generated lesions that were substrates for enzymes belonging to the BER pathway. In addition, in vitro studies indicated that the DNA damage produced by the flavonoid-enriched fractions was also a substrate for exonuclease III and that the phosphodiester breakage was amplified by copper ions. These results indicate that flavonoids from the pepper tree (Schinus terebinthifolius, Raddi) generate lesions on DNA that are potential targets of FPG and MutY glycosylase from the BER pathway. Chromatographic and spectral analyses helped to support the hypothesis that the flavonoids of the Brazilian pepper tree bark are the main factors involved in the fraction's damage potential. The isolated flavonoids from Fraction II were also tested in vitro and support the oxidative damage potential of these flavonoids. PMID- 17722087 TI - Antimicrobial preservative use in parenteral products: past and present. AB - The following review provides a comprehensive summary of antimicrobial preservatives that are commonly used in licensed parenteral products to date. The information reviewed includes the general properties of the preservatives, the doses and frequency of their use, the classes of the preserved products (peptide, protein, vaccine, and small molecule products), the interactions with other formulation components, and the criteria commonly used for their selection in parental product formulations. It was revealed that phenol and benzyl alcohol are the two most common antimicrobial preservatives used in peptide and protein products, while phenoxyethanol is the most frequently used preservative in vaccines. Benzyl alcohol or a combination of methylparaben and propylparaben are generally found in small molecule parenteral formulations. The key criteria for antimicrobial preservative selection are the preservative's dose, antimicrobial functionality, and effect on the active ingredient. Additionally, the use of spectroscopic techniques (circular dicroism (CD) and fluorescence) and differential scanning calorimetry (DSC) were identified as common techniques used in evaluating an antimicrobial preservative for its impact on the conformational stability of peptide, protein, and vaccine antigens. The future use of preservatives is also discussed, including antimicrobial agents such as peptides, and regulatory requirements for antimicrobial effectiveness testing. PMID- 17722091 TI - Improving the growth rate of Escherichia coli DH5alpha at low temperature through engineering of GroEL/S chaperone system. AB - GroEL/S is a molecular chaperone system in Escherichia coli which not only assists the folding of intracellular proteins but also affects the cellular activity against the change of environmental condition. Here we show that the growth rate of E. coli DH5alpha can be improved at low temperature by expressing a GroEL/S variant achieved through irrational protein engineering approach. The GroELS variant (GroELS(var)) accelerating the growth of E. coli DH5alpha was screened through enrichment culture of the mutant libraries obtained by random mutagenesis. E. coli DH5alpha harboring the groELS(var) gene exhibited approximately 1.5-2 times higher growth rate compared to the strain with wild type GroELS at 15-30 degrees C. At 10 degrees C, a temperature that the growth of E. coli DH5alpha almost stops, the GroELS(var) triggered the growth of E. coli DH5alpha. We identified that seven nucleotides of groELS gene and six amino acids of the GroELS were changed through the mutagenesis and screening. Site directed mutagenic analysis revealed that H360 in GroEL(var) is the most crucial residue determining the activity of GroELS(var) and more than one of the other residues in GroEL(var) may be additionally involved in the activity of GroELS(var). The improvement of growth rate induced by the GroELS(var) was observed only in the strain DH5alpha and not detected in other E. coli strains, such as BL21, BW25113, codon+, JM110, Top10, and XL1-blue. PMID- 17722090 TI - Internal kinematics of the tongue during feeding in pigs. AB - Six ultrasonic crystals (O2 mm) were implanted into the tongue body to form a wedge-shaped configuration in six 12-week-old Yucatan minipigs. These crystals allow recording of the distance changes in bilateral lengths (RL/LL) and base thicknesses (RT/LT), and anterior (AW) and posterior (dorsal and ventral, PDW and PVW) widths during natural feeding. Results indicated that changes in all measured dimensions were stereotypical with considerable regularity. The greatest dimensional changes during chewing were seen in the AW (33.3%), significantly larger than those in other dimensions (P < 0.05-0.001). During ingestion, change in all widths and thicknesses reduced significantly compared with those during chewing (P < 0.05), but changes in the lengths (RL/LL) were significantly larger than those during chewing (P < 0.01). During drinking, overall dimensional changes reduced and amplitudes were symmetrically distributed in all dimensions. The timing analysis indicated that, during chewing, the reversal of dimensional decrease to increase in the PVW occurred first, followed by those of PDW, AW, RT/LT, and RL/LL (P < 0.05). During ingestion, the AW started widening first. Time sequence of these reversals during drinking was similar to that during chewing, but RT/LT thickening was behind RL/LL lengthening. These results suggested that during natural feeding, regional tongue deformations are rhythmic and stereotypical similar to jaw movement. The reversals of expansion-contraction of various dimensions are not synchronous, but occur in a sequential manner in timing. Tongue internal deformations are task-specific in both timing and amplitude. The dimensional expansions-contractions are dominant in the transverse and sagittal planes during chewing and ingestion, respectively, but are smaller and more symmetrically distributed across various dimensions during drinking. PMID- 17722092 TI - Ultrastructure and estrogen regulation of the lymphatic stomata of ovarian bursa in mice. AB - The ovarian bursa is a key player in maintaining adaptive ovarian microenvironment for ovulation. The lymphatic stomata are believed to be a major contributor to execute the function of the ovarian bursa, whereas little is known about their ultrastructure and regulation. Here, we examined the ultrastructure of lymphatic stomata in mouse ovarian bursa by scanning electron microscopy and transmission electron microscopy and investigated its regulation by estrogen. We found that the mesothelium on the visceral layer of mouse ovarian bursa was composed of the cuboidal and flattened cells. The lymphatic stomata with round and oval shapes were mainly among the cuboidal cells. The particles, cells, and fluid passed through the stomata and entered into the lymphatic drainage unit composed of connective tissue and lymphatic endothelial cells beneath the stomata. We also used trypan blue as a tracer and found that the absorption of trypan blue through the lymphatic stomata was increased by estrogen that enlarged the average opening area of lymphatic stomata. Furthermore, we detected that there existed estrogen receptors in the nuclei of the mesothelial cells on the visceral ovarian bursa by using immunoelectron microscopy. Taken together, these data suggest that both the absorption and opening area of the lymphatic stomata in mouse ovarian bursa may be influenced by estrogen. PMID- 17722093 TI - Prediction of diffusion coefficients of plasmids. AB - The ability to predict diffusion coefficients is important in the design, analysis, and operation of plasmid downstream processing operations such as membrane and fixed-bed chromatography. A correlation is proposed to predict the diffusion coefficient, D, of supercoiled plasmid DNA molecules in dilute solutions on the basis of the molecular weight, M, or size. Experimental data (18 points) collected from the literature confirmed the proposed variation of D with plasmid molecular weight as D proportional, variant M(-2/3), for molecules within the 1,800-287,100 base-pair range. The correlation was able to estimate the available experimental results with an average error of 6.3%. PMID- 17722094 TI - Leisure-time physical activity patterns and risk of colon cancer in women. AB - Although physical activity has been consistently associated with lower risk of colon cancer, many details of the relationship remain unclear. We assessed the relation between physical activity and risk of colon cancer in 79,295 women aged 40-65 who were free of cancer, ulcerative colitis and Crohn's disease and who reported their leisure-time physical activity in 1986; 547 cases were identified through 2002. Women who expended more than 21.5 metabolic equivalent hr/week of physical activity had a relative risk (RR) of colon cancer of 0.77 (95% CI 0.58 1.01), compared to women who expended <2 metabolic equivalent hr/week. The association was stronger for distal than proximal tumors. Among women whose only reported activity was walking, there was a decreased risk of colon cancer in women walking 1-1.9 hr/week (RR = 0.69, 95% CI 0.47-1.03) compared to those who did not walk. Results were similar for increased amounts of walking, but there was no evidence of a dose response relation. Among women who participated in moderate or vigorous activity, increasing hours of activity were also associated with a decreased risk of colon cancer (p for trend = 0.01); women exercising >4 hr/week had a 40% lower risk of colon cancer than those exercising <1 hr/week (RR = 0.56, 95%CI 0.33-0.94). Long-term physical activity was not associated with risk of colon cancer, but the number of cases was small. A significant inverse association exists between physical activity, including that of moderate intensity, such as walking, and risk of colon cancer in women that is more pronounced for distal tumors. PMID- 17722096 TI - Risk of lung cancer following exposure to carbon black, titanium dioxide and talc: results from two case-control studies in Montreal. AB - The International Agency for Research on Cancer (IARC) recently evaluated the carcinogenicity of three poorly soluble weakly-toxic substances: carbon black, titanium dioxide and talc. Though there is evidence of carcinogenity in experimental animals for these substances, the evidence in humans is sparse and equivocal. In the context of two large population based case-control studies of lung cancer carried out in Montreal, we were able to study the possible relationships between the exposure to each of these substances and subsequent risk of lung cancer. We were able to distinguish talc used for industrial purposes from that used for cosmetic purposes. Interviews for Study I were conducted in 1979-1986 (857 cases, 533 population controls, 1,349 cancer controls) and interviews for Study II were conducted in 1996-2001 (1,236 cases and 1,512 controls). Detailed lifetime job histories were elicited, and a team of hygienists and chemists evaluated the evidence of exposure to a host of occupational substances. Lung cancer risk was analysed in relation to each exposure, adjusting for several potential confounders, including smoking. Subjects with occupational exposure to carbon black, titanium dioxide, industrial talc and cosmetic talc did not experience any detectable excess risk of lung cancer. The results are consistent with the recent evaluations of the IARC Monographs. PMID- 17722095 TI - Organochlorines and risk of non-Hodgkin lymphoma. AB - Organochlorine chemicals and polychlorinated biphenyls (PCBs) have been suspected as possible risk factors for non-Hodgkin lymphoma (NHL). We investigated PCBs and organochlorine pesticides and risk of NHL in a population-based case-control study in British Columbia, Canada. Congeners of PCBs (including dioxinlike congeners) and pesticides or pesticide metabolites were measured in plasma of 422 pretreatment cases and 460 control subjects. This is so far the largest study to examine organochlorines in plasma to date. Several dioxin-like PCB congeners were associated with increased risk of NHL, including dioxin-like PCB nos. 118 and 156 with odds ratios (OR) for the highest versus lowest quartile between 1.6 and 1.8. Several non-dioxin-like congeners also showed significant associations. The PCB congener with the strongest association was no. 180 with an OR for the highest versus the lowest quartile of 1.83 (95% confidence interval = 1.18-2.84). Six pesticide analytes also showed a significant association with NHL; beta hexachlorocyclohexane, p,p'-DDE, hexachlorobenzene, mirex, oxychlordane and trans nonachlor. The strongest association was found for oxychlordane, a metabolite of the pesticide chlordane (highest vs. lowest quartile OR = 2.68, 95% confidence interval = 1.69-4.24). Our results provide further evidence that organochlorines contribute to NHL risk. PMID- 17722097 TI - Conjunctival lymphoid follicles in new world rodents. AB - We report for the first time, the detection of conjunctival lymphoid follicles (CLF) in the eyes of New World rodents. CLF were found in 7 of the 15 species examined, 6 of the 10 genera, and in at least one individual in four families of rodents. These follicles are dense collections of leukocytes in the conjunctival substantia propria with a thinned overlying epithelium lacking in goblet cells. Although the precise location of CLF within the conjunctiva varied from species to species, all CLF were found in the fornix of the conjunctival sac. In general, size and complexity of CLF varied with the size of the eye; the larger the eye, the larger and more complex the CLF. Our findings also reveal that some species of New World rodents, like the majority of Old World rodents examined in this and previous studies might lack CLF. However, until larger samples are examined, this is difficult to state with certainty. Consequently, the presence/absence of CLF at this point might not be informative for phylogenetic comparisons. Our findings also suggest the deer mouse, Peromyscus maniculatus, might serve as a useful model species for studying ocular infections and immunology of the eye. PMID- 17722098 TI - PLGA nanoparticles for oral delivery of hydrophobic drugs: influence of organic solvent on nanoparticle formation and release behavior in vitro and in vivo using estradiol as a model drug. AB - The aim of present investigation was to screen different solvents for optimizing nanoparticle preparation in terms of particle size, entrapment efficiency, and finally, release behavior using a model drug estradiol. Nanoparticles were prepared following emulsion-diffusion-evaporation method using didodecyldimethyl ammonium bromide (DMAB) or polyvinyl alcohol (PVA) as stabilizers. Ethyl acetate (EA), acetone (ACE), chloroform (CHL), and dichloromethane (DCM) were used as organic solvents either individually or in combinations. DMAB when used as surfactant led to smaller particle size as compared to PVA irrespective of the solvents and combinations used, but on the other hand, PVA produced particles with higher entrapment when combinations of solvents used. DCM in combination with EA resulted in highest entrapment with both the stabilizers. All the formulations exhibited similar in vitro release profile (Zero order) irrespective of stabilizer (DMAB or PVA) used, however, the average release per day was higher in case of DCM formulations due to greater entrapment. In situ uptake studies suggest that smaller the particle size better is the uptake. The bioavailability from nanoparticles was assessed in male Sprague Dawley (SD) rats at a dose of 1 mg drug/rat. EA/DMAB (size 116.0 +/- 2.6 nm) and DCM:EA 70:30/DMAB (size 253.0 +/ 5.5 nm) showed the release for 9 and 5 days, respectively, whereas EA/PVA (size 279.3 +/- 2.5 nm) released the drug over the periods of 3 days suggesting that particle size has significant role in determining the fate of nanoparticles in vivo. Histopathological examination revealed absence of any inflammatory response with the formulations under the studied period. PMID- 17722099 TI - Pharmacokinetic prediction for intravenous beta-lactam antibiotics in pediatric patients. AB - A method for predicting pharmacokinetics in pediatric patients for intravenous beta-lactam antibiotics is proposed. We focused on the allometric relationships of pharmacokinetic parameters with individual body weights (BW) in human including healthy adults and pediatric patients. Drug concentration data for 15 intravenous beta-lactam antibiotics were collected retrospectively from the published articles and the individual pharmacokinetic parameters were re calculated. A mixed effect modeling (MEM) was applied for the allometric relationship for those beta-lactam antibiotics, and mean and variances of inter drug variability for the allometric parameters and also variance for intra-drug (residual) variability were estimated. Then drug-specific allometric parameters were estimated by an empirical Bayesian method using the pharmacokinetic parameters for a drug only in healthy adults as observations, and finally the individual pharmacokinetic parameters in pediatric patients were predicted. The predictability of the method was evaluated by the leave-one-out method. We also demonstrated a method for simulating plasma concentration-time profiles in pediatric patients, and the predicted time-course curves generally coincided well with the actual plasma concentration data for the tested drugs. PMID- 17722100 TI - Role of thermodynamic, molecular, and kinetic factors in crystallization from the amorphous state. AB - Though there is an advantage in using the higher solubility amorphous state in cases where low solubility limits absorption, physical instability poses a significant barrier limiting its use in solid oral dosage forms. Unlike chemical instability, where useful accelerated stability testing protocols are common, no methodology has been established to predict physical instability. Therefore, an understanding of the factors affecting crystallization from the amorphous state is not only important from a scientific perspective but also has practical applications. Crystallization from the amorphous matrix has been linked to the molecular mobility in the amorphous matrix and recent research has focused on developing the link between these two fundamental properties of glass forming materials. Although researchers have been actively working in this area for some time, there is no current review describing the present state of understanding of crystallization from the amorphous state. The purpose of this review therefore is to examine the roles of different factors such as molecular mobility, thermodynamic factors, and the implication of different processing condition, in crystallization from the amorphous state. We believe an increased understanding of the relative contributions of molecular mobility and processing conditions are vital to increased usage of the amorphous state in solid oral dosage forms. PMID- 17722101 TI - Process analytical technology (PAT): quantification approaches in terahertz spectroscopy for pharmaceutical application. AB - Terahertz (THz) spectroscopy and chemometric analysis of resultant absorption spectra in the 30-500 cm(-1) range has been applied to perform quantitative determination of both active ingredient and excipient concentrations of tablets. Tests were performed on a series of tablets composed of various concentrations and processes of theophylline formulated with lactose, magnesium stearate, starch or Avicel, and as a function of tablet hardness. Transmission spectra of polyethylene pellets derived from each of the samples were analyzed using three approaches. Spectral superposition method was used as an indirect measure to examine whether and when the interaction among various pharmaceutical components and the tableting history could be considered insignificant for quantification purpose. Spectral characteristic peak method was able to correlate peak maxima with correction for tablets having the same hardness. Multivariate analysis (PCR and PLS 1) was capable of correlating THz spectra with tablet concentrations. The predicted concentrations of independent samples using multivariate models agreed well with nominal concentrations. The best correlations were obtained using multivariate analysis. With these studies, the advantage of using multivariate approach was demonstrated for process analytical technology (PAT) application. Further, the feasibility of integrating THz spectroscopy and chemometrics for the purpose of quantifying pharmaceutical tablet concentrations was demonstrated. PMID- 17722102 TI - Liposomal coencapsulated fludarabine and mitoxantrone for lymphoproliferative disorder treatment. AB - Fludarabine (FLU)-based combination therapies are commonly used to treat low grade lymphoma and chronic lymphocytic leukemia (CLL) patients. In vitro and clinical studies have indicated advantages when FLU and mitoxantrone (MTO) are applied in combination. To further enhance this effect, these two agents were coencapsulated in liposomes. FLU was passively encapsulated during liposome formation, and MTO was loaded with a transmembrane pH gradient. Entrapment efficiency, particle size, stability, and drug release kinetics were characterized. In vitro cytotoxicity study was carried out in two representative B-cell lines: Wac3CD5 and Raji. Synergism as measured by combination index (CI) was observed in cells treated with liposomes coencapsulating FLU and MTO. Annexin V/propidium iodide (PI) analysis further confirmed that coencapsulated FLU and MTO improved the percentage of apoptosis among primary CLL cells. These data suggest that adopting liposomes containing coencapsulated drug combinations constitutes a potential strategy to promote drug synergism and may have utility in the treatment of leukemia and lymphoma. PMID- 17722103 TI - Investigation of DNA-binding properties of organic molecules using quantitative structure-activity relationship (QSAR) models. AB - Due to the great potential of DNA as a receptor, many classes of synthetic and naturally occurring molecules exert their anticancer activities through DNA binding. In the field of antitumor DNA-binding agents, a number of acridine and anthracycline derivatives are in the market as chemotherapeutic agents. However, the clinical application of such classes of compounds has encountered problems such as multi-drug resistance and secondary and/or collateral effects. Thus, there has been increasing interest in discovering and developing small molecules that are capable of DNA-binding, which will be expected to be used either in place of or in conjunction with, the existing compounds. The interest in the application of the QSAR paradigm has steadily increased in recent decades and we hope it may be useful in the design and development of DNA-binding molecules as new anticancer agents. In the present review, an attempt has been made to understand the DNA-binding properties of different compound series and discussed using 27 QSAR models, which reveal a number of interesting points. The most important determinants for the activity in these models are Hammett electronic (sigma and sigma+), hydrophobic, molar refractivity, and Sterimol width parameters. PMID- 17722104 TI - The transient dermal exposure: theory and experimental examples using skin and silicone membranes. AB - A diffusion model is presented to account for the disposition of chemicals applied to skin as transient exposures. Two conditions are considered that apply to the skin surface following the exposure period, which are applicable to chemicals exhibiting two extremes of chemical volatility. For one case, representing highly volatile compounds, the solution is generalized to apply to multiple transient exposures. For both cases, algebraic expressions are derived to calculate the total amount of chemical that penetrates the skin. The theory is applied to experimental measurements of the in vitro penetration of diethyl phthalate applied to hairless guinea pig (HGP) skin and silicone rubber membranes (SRMs) as transient exposures. The transient exposure theory ably models the experimental data, with coefficients of determination greater than 0.97 (HGP) and greater than 0.99 (SRM). The ability of parameters derived from concurrent infinite dose experiments to predict the time course of absorption from transient exposures is explored. Discrepancies were found between measured cumulative penetration of chemical from transient exposure experiments and penetration predicted from parameters derived from infinite dose experiments, particularly for HGP. Possible reasons are explored. The current model may provide a realistic framework for estimating absorption from occupational, environmental and pharmaceutical dermal exposures. PMID- 17722105 TI - The effect of a point mutation on the stability of IgG4 as monitored by analytical ultracentrifugation. AB - There is presently considerable interest in the state of aggregation and biophysical integrity of antibody preparations, and recent advances in the analysis of data from the analytical ultracentrifuge renders it a powerful probe of these stability phenomena, under both storage and freeze-thaw conditions. Solutions of a wild-type IgG4 antibody and a single amino acid hinge mutant IgG4m (serine residue 241 converted to proline) were exposed to different accelerated stress conditions, namely (i) elevated temperature storage for various periods (up to 59 days at 37 degrees C) or (ii) a series of freeze-thaw cycles (storage at -80 degrees C then incubation at 20 degrees C for 1 h under different conditions). Analysis using the nondisruptive probe of sedimentation velocity in the analytical ultracentrifuge indicated that for both antibodies the monomer was always the most common species present whatever storage regime had been used. Sedimentation coefficient distribution analysis showed that other higher oligomer species and half-antibodies were present, and appeared to be not in chemical equilibrium with each other. Solution heterogeneity was found to increase considerably with treatment for both native and hinge-mutant antibodies although the latter appeared to be more resistant to freeze-thaw-induced aggregation. PMID- 17722106 TI - Absence of effect of power-frequency magnetic fields exposure on mouse embryonic lens development. AB - There are no reports in the literature investigating the biological effect of power-frequency (50/60 Hz) magnetic fields on embryonic lens development. We investigated whether power-frequency magnetic fields act as an environmental insult and induce changes in morphology or protein and/or transcription factor mRNA expression levels in developing mouse embryonic lenses. Three groups of pregnant mice were exposed to magnetic fields (50 Hz) of varying intensities (0.0, 1.5, and 4.5 mT) for 3 h per day from gestation day (GD) 0 to 18. The embryonic lenses were enucleated on GD 18. The lenses in the three groups were found to be transparent and the lens epithelial cells from the experimental groups exhibited normal ultrastructure comparable to the control. No significant differences were found among the three groups in quantity of water soluble protein (WSP), water insoluble protein (WIP), the ratio of WIP to total protein, and the mRNA expression levels of four well known developmentally regulated DNA binding transcription factors: Pax6, Prox1, Sox1, and c-maf. We preserved one pregnant mouse per group, fed the neonatal mice until 2 weeks of age, and then found the lenses transparent. Our results did not detect any effects on the development of embryonic lenses in mice exposed to power-frequency magnetic fields. PMID- 17722107 TI - The role of chromosomal alterations in human cancer development. AB - Cancer cells become unstable and compromised because several cancer-predisposing mutations affect genes that are responsible for maintaining the genomic instability. Several factors influence the formation of chromosomal rearrangements and consequently of fusion genes and their role in tumorigenesis. Studies over the past decades have revealed that recurring chromosome rearrangements leading to fusion genes have a biological and clinical impact not only on leukemias and lymphomas, but also on certain epithelial tumors. With the implementation of new and powerful cytogenetic and molecular techniques the identification of fusion genes in solid tumors is being facilitated. Overall, the study of chromosomal translocations have revealed several recurring themes, and reached important insights into the process of malignant transformation. However, the mechanisms behind these translocations remain unclear. A more thorough understanding of the mechanisms that cause translocations will be aided by continuing characterization of translocation breakpoints and by developing in vitro and in vivo model systems that can generate chromosome translocation. PMID- 17722109 TI - Molecular classification system identifies invasive breast carcinoma patients who are most likely and those who are least likely to achieve a complete pathologic response after neoadjuvant chemotherapy. AB - BACKGROUND: The molecular classification system categorizes invasive breast carcinomas according to their key driving biomarkers. In the current study, the authors evaluated whether response to neoadjuvant chemotherapy was correlated with the molecular classification groups. METHODS: Using immunohistochemistry, the molecular classification group (luminal-A, luminal-B, HER-2-variant, HER-2 classic, and basal phenotype) was retrospectively determined in 68 breast cancer patients who received neoadjuvant treatment. RESULTS: A total of 28 carcinoma patients (41.2%) achieved a compete pathologic response (CPR), including 2 of 15 patients classified as having luminal-A (13.3%), 4 of 16 patients classified as having luminal-B (25.0%), 10 of 12 patients classified as having HER-2-classic (83.3%), none of the 4 patients classified as having HER-2-variant, and 12 of 21 patients classified as having basal phenotype (57.1%) neoplasms. The CPR rate among patients with the HER-2-classic and basal neoplasms was 67% (22 of 33 neoplasms), compared with 17.1% (6 of 35 neoplasms) in the non-HER-2 classic/basal combined group (P < .001). Eleven carcinomas were initially diagnosed as invasive lobular carcinomas (pleomorphic and classic), 4 of which were luminal-A, 4 of which were luminal-B, 2 of which were HER-2-classic, and 1 of which was basal. On review, only 3 of these 11 cases remained classified as classic lobular carcinoma, all of which were classified as luminal-A, and none of these patients achieved a CPR. Four of the other 8 patients achieved a CPR. CONCLUSIONS: The molecular classification system is useful for identifying carcinoma patients who are most likely and those who are least likely to achieve a CPR. In the current study, all the morphologically classic lobular carcinomas were classified as luminal-A neoplasms, which may explain the low rate of CPR reported. PMID- 17722110 TI - Upper tract transitional cell carcinoma: finding a way forward. PMID- 17722108 TI - Puralpha as a cellular co-factor of Rev/RRE-mediated expression of HIV-1 intron containing mRNA. AB - To ensure successful replication, HIV-1 has developed a Rev-mediated RNA transport system that promotes the export of unspliced genomic RNA from nuclei to cytoplasm. This process requires the Rev responsive element (RRE) that is positioned in the viral transcript encoding Env protein, as well as in unspliced and singly spliced viral transcripts. We identified Puralpha, a single-stranded nucleic acid binding protein as a cellular partner for Rev that augments the appearance of unspliced viral RNAs in the cytoplasm. A decrease in the level of Puralpha expression by siRNA diminishes the level of Rev-dependent expression of viral RNA. Through its nucleic acid binding domain, Puralpha exhibits the ability to interact with the multimerization and RBD domains of Rev. Similar to Rev, Puralpha associates with RRE and in the presence of Rev forms a complex with slower electrophoretic mobility than those from Rev:RRE and Puralpha:RRE. The interaction of Puralpha with RRE occurs in the cytoplasm where enhanced association of Rev with RRE is observed. Our data indicate that the partnership of Puralpha with Rev is beneficial for Rev-mediated expression of the HIV-1 genome. PMID- 17722111 TI - Trends in cervical cancer mortality in Korea 1993-2002: corrected mortality using national death certification data and national cancer incidence data. AB - Cervical cancer is a major health problem for Korean women, accounting for 9.8% of new female cancer cases, even though incidence rates have been decreasing. The Korean cervical cancer mortality rate for 1993-2002 based on National Statistical Office data shows an increasing trend, but the actual rates are thought to have decreased by epidemiologists, clinicians and other cancer experts. To explain this gap and solve this problem, we corrected the number of cervical cancer deaths by comparing death certificate cases of unspecified uterine cancer data with the national cancer incidence databases of entire cancer registries in Korea. We used 2 different methods to make a correction. First, we considered "uterus, unspecified" deaths previously registered as "cervix, uterine" cases misclassified and added them to the cervical cancer deaths. Alternatively, we multiplied the total number of registered unspecified uterine cancer deaths by age-specific proportions of registered incident cervical cancer cases among all cancers and added the product to cervical cancer deaths. The overall corrected age-standardized cervical cancer mortality rates per 100,000 women decreased from 5.2 in 1993 to 3.9 in 2002 (estimated annual percentage change (EAPC): -4.05%, 95% CI: -4.88, -3.22). While cervical cancer mortality showed a decreasing tendency in women aged 30-69 years, it increased substantially in women aged > or =70 years (EAPC: 3.62%, 95% CI: 1.92-5.35). Results of this study will provide evidence-based foundation for the evaluation of the existing cervical cancer screening programs. PMID- 17722113 TI - Evaluation of the reliability of nonlinear optimal solutions in pharmaceuticals using a bootstrap resampling technique in combination with Kohonen's self organizing maps. AB - The response surface method incorporating multivariate spline interpolation (RSM S) is a powerful technique for the formulation optimization of pharmaceuticals. However, no satisfactory method has been developed to evaluate the reliability of the optimal solution. We integrated bootstrap (BS) resampling and Kohonen's self organizing maps (SOM) into RSM-S using the formulation optimization of theophylline tablets as the model experiment. The hardness and the 63.2% drug release times of the tablets were measured as response variables. Based on the data set obtained, the simultaneous optimal solution was estimated using RSM-S. Leave-one-out cross-validation showed the optimal solution to be reliable. Concurrently, a large number of BS samples were generated from the original data set using BS resampling, and simultaneous optimal solutions for each BS sample (BS optimal solutions) were estimated. The distribution of the BS optimal solutions was far from a normal distribution, suggesting a mixture of global and local optimal solutions. SOM clustering was used to identify the set of global optimal solutions. SOM clustering divided the BS optimal solutions into several clusters, and the reliability of the optimal solution was evaluated from the cluster that included the optimal solution. This study offers a promising method for evaluating the reliability of nonlinear optimal solutions. . PMID- 17722114 TI - Caspase inhibitor facilitates recovery of hearing by protecting the cochlear lateral wall from acute cochlear mitochondrial dysfunction. AB - We recently showed that acute energy failure in the rat cochlea induced by local administration of the mitochondrial toxin 3-nitropropionic acid (3-NP) causes hearing loss mainly due to degeneration of cochlear lateral-wall fibrocytes. In the present study, we analyzed the effect of the pan-caspase inhibitor z-Val-Ala Asp(Ome)-fluoromethylketone (Z-VAD-FMK) on 3-NP-induced hearing loss in a model showing temporary threshold shifts at low frequencies and permanent threshold shifts at high frequencies. The model rats received an intraperitoneal injection of either Z-VAD-FMK or vehicle for 3 days starting 1 day prior to 3-NP treatment. One day after the administration of 3-NP, the auditory brain-stem response (ABR) threshold at 20 kHz was elevated to 70 dB in the Z-VAD-FMK group and to 85 dB in controls. The Z-VAD-FMK group completely recovered to the preoperative level within 14 days, whereas in the controls, the ABR threshold remained elevated at 50 dB even 28 days after the administration of 3-NP. Treatment with Z-VAD-FMK also improved recovery of hearing at 8 kHz but did not change recovery at 40 kHz. Histological examination demonstrated that treatment with Z-VAD-FMK inhibited progressive degeneration of the lateral-wall fibrocytes in the cochlear basal turn, as well as apoptosis of these fibrocytes. These results clearly indicate that caspase-dependent apoptosis of fibrocytes in the cochlear lateral wall plays an important role in hearing loss in the present animal model. Moreover, the results of the present study suggest that systemic administration of a caspase inhibitor may be an effective therapy for sensorineural hearing loss caused by acute energy failure such as that observed in cochlear ischemia. PMID- 17722112 TI - High load for most high risk human papillomavirus genotypes is associated with prevalent cervical cancer precursors but only HPV16 load predicts the development of incident disease. AB - Cervicovaginal human papillomavirus (HPV) viral load has been purported as a potential marker for the detection of high-grade cervical intraepithelial neoplasia or cancer (>/=CIN2). To examine disease association with type-specific viral load for the full-range of anogenital HPV infections, we conducted cross sectional and prospective analyses of approximately 2,000 HPV-infected women from a 10,000-woman population-based study in Guanacaste, Costa Rica with 7 years of follow-up. Cervical specimens were tested for >40 HPV types using a MY09/MY11 L1 consensus primer PCR method with type-specific dot blot hybridization and PCR signal intensity as a measure of viral load. A positive association was observed between prevalent >/=CIN2 and high viral load compared to low viral load for women with baseline single HPV16 infections (OR = 19.2, 95% CI = 4.4-83.2) and single non-16 carcinogenic infections (OR = 9.2, 95% CI = 2.1-39.9). Inclusion of women with multiple HPV types did not substantially change these associations. In prospective follow-up, only women infected with HPV16 alone (OR = 27.2, 95% = 3.5 213.5) had a strong association between high viral load and incident >/=CIN2; non 16 carcinogenic high viral load was not associated with incident >/=CIN2 (OR = 0.7, 95% CI = 0.2-1.9). Single noncarcinogenic type viral load was not associated with increased risk of prevalent or incident >/=CIN2 (OR = 1.2 and 1.1, respectively). In conclusion, carcinogenic high viral load was associated with prevalent >/=CIN2; however HPV16 was uniquely associated with incident >/=CIN2. The extent to which these observations can be translated into clinical practice must be rigorously examined in the context of the method of viral load measurement and the type-specific differences observed for incident >/=CIN2. PMID- 17722115 TI - Broncholithiasis in an immune compromised boy with disseminated Mycobacterium kansasii. AB - A case of broncholithiasis in a child is reported. To our knowledge, it has not been reported in children. Broncholithiasis is a condition in which a peribronchial calcified lymph node erodes into or distorts an adjacent bronchus. Symptoms of broncholithiasis include cough, recurrent episodes of fever, haemoptysis, and purulent sputum. The most common cause of broncholithiasis is Mycobacterium tuberculosis (M. tuberculosis). Here we describe a 14-year-old boy known to have disseminated Mycobacterium kansasii (M. kansasii) infection associated with hypoplastic myelodysplastic syndrome (MDS). He was presented with cough and fever. Computed tomography (CT) and bronchoscopy revealed a large calcified mass eroding in the right main bronchus. While surgical therapy was considered, haemoptysis developed and his condition deteriorated. Bone marrow puncture revealed acute myeloid leukemic transformation of the MDS. Curation was no longer possible. Post mortem examination revealed a large bronchiolith, evolving from a calcified lymph node. PMID- 17722116 TI - Risk factors for the development of bronchiectasis in HIV-infected children. AB - Our objective was to describe the risk factors for the development of bronchiectasis in HIV-1 infected children. This study was a retrospective, case controlled study based upon medical record review of HIV-1 infected children receiving primary care at a single large, urban medical center in Miami, Florida. Cases (HIV-1 infected children who developed bronchiectasis while being cared for between January 1982 and September 2000) were matched 1:3 (birth +/- 24 months) with controls (HIV-1 infected children without bronchiectasis). Variables analyzed including number of episodes of pneumonia (including Pneumocystis jiroveci pneumonitis [PCP], lymphoid interstitial pneumonitis (LIP), and CDC category of immunosuppression) were noted in both cases and controls until the age at which the cases developed bronchiectasis. Of the 749 patients whose charts were reviewed, 43 met the case definition for bronchiectasis and 19 met the eligibility criteria for this study. Fifty-seven controls were randomly selected from the patients without bronchiectasis. Cases were more likely to have experienced recurrent pneumonia than the controls; 17 (89.5%) versus 5 children (8.8%) respectively (P-value 10 mg/l). An increased CRP at baseline was the only variable explaining the retention rate in the Cox model (p = 0.003, hazard ratio = 3.3, 95% CI 1.5-7.3). CONCLUSION: Interruption for expert opinion of inefficacy was more frequent for patients with low baseline CRP; however, even in these patients retention was high. Increased CRP should not be considered mandatory for proposing TNF blocker treatment in axial AS. PMID- 17722226 TI - Specific proteins identified in whole saliva from patients with diffuse systemic sclerosis. AB - OBJECTIVE: To evaluate the global changes of salivary protein profiles in patients with systemic sclerosis (SSc) using a proteomic approach. METHODS: Whole saliva (WS) was collected from 15 patients with diffuse SSc and 15 healthy volunteers. Protein expression profiles for each sample were generated by 2 dimensional gel electrophoresis, and protein spots of interest were identified using peptide mass fingerprinting. RESULTS: The level of all the most representative salivary proteins except keratin 6L remained unchanged and only qualitative differences were observed between control subjects and patients with SSc. A total of 19 spots were found in SSc that were not matched with the controls. Fourteen out of a total of 19 spots were identified by mass analysis and were found to collapse into 9 unique proteins. These spots were identified to be cyclophilin A, calgranulin B, psoriasin, beta2-microglobulin, calgranulin A, glyceraldehyde-3-phosphate dehydrogenase, triose phosphate isomerase (TPI), actin related protein 2/3 complex subunit 2 (Arp2/3 complex), and cystatin B. CONCLUSION: Our study is the first reporting the WS protein pattern of patients with SSc and comparing the differences between WS of patients with SSc and WS of healthy subjects. Both previously identified and newly identified proteins were detected in WS using a proteomic approach. Some of these proteins, like keratin 6L, psoriasin, TPI, and Arp2/3 complex, might have a pathological significance for SSc. It is possible that some of them can be defined as new therapeutic targets or diagnostic markers for SSc disease. PMID- 17722228 TI - Mucocutaneous lesions of Behcet's disease. AB - Behcet's disease is particularly prevalent in "Silk Route" populations, but it has a global distribution. The diagnosis of the disease is based on clinical criteria as there is as yet no pathognomonic test, and mucocutaneous lesions, which figure prominently in the presentation and diagnosis, may be considered the diagnostic hallmarks. Among the internationally accepted criteria, painful oral and genital ulcers, cutaneous vasculitic lesions and reactivity of the skin to needle prick or injection (the pathergy reaction) are considered hallmarks of Behcet's disease, and often precede other manifestations. Their recognition may permit earlier diagnosis and treatment, with salutary results. This paper describes the various lesions that constitute the syndrome and focuses on those that may be considered characteristic. PMID- 17722230 TI - Diagnosis of overt disseminated intravascular coagulation: a comparative study using criteria from the International Society versus the Korean Society on Thrombosis and Hemostasis. AB - PURPOSE: Since 1993, Koreans have used diagnostic criteria set by the Korean Society on Thrombosis and Hemostasis (KSTH) in the diagnosis of overt disseminated intravascular coagulation (DIC). In 2001, the Scientific and Standardization Committee (SCC) of the International Society on Thrombosis and Hemostasis (ISTH) proposed new diagnostic criteria for the diagnosis of overt DIC. We wanted to compare the use of the ISTH versus KSTH criteria in the diagnosis of overt DIC. MATERIALS AND METHODS: We enrolled 131 patients over the age of 15 years, who had been admitted and diagnosed as having DIC from May 2000 to April 2005 at the Youngdong Severance Hospital, Seoul, Korea. Of the 131 patients, there were 71 males and 60 females, with a median age of 61 years. Hemostatic tests, including platelet counts, PT, aPTT, fibrinogen level and D dimer, were evaluated based on the respective scoring systems. To assess the concordance between the two diagnostic systems, we used the Student's t-test and the K-coefficient. RESULTS: There were 79 patients compatible with the ISTH criteria and 63 patients with the KSTH criteria. Sixty-one patients were compatible with both diagnostic systems. The grade of agreement, or concordance rate, was 84.7% and the K-coefficient, or interrater reliability, was as low as 0.6 without significance. However, if we scored 1 point for a fibrinogen level of 100-150 mg/dL, and 2 points for a level below 100 mg/dL, for the ISTH criteria, then 63 patients were compatible with both diagnostic systems, and the concordance rate increased to 85.5% and the K-coefficient to 0.71 with significance. CONCLUSION: To achieve good agreement between the ISTH and KSTH diagnostic systems for overt DIC, we highly recommend changing the plasma fibrinogen cut-off value in the ISTH criteria from 100mg/dL to 150 mg/dL and scoring up to 2 points for a level below 100 mg/dL. PMID- 17722229 TI - Avian influenza: should China be alarmed? AB - Avian influenza has emerged as one of the primary public health concern of the 21st century. Influenza strain H5N1 is capable of incidentally infecting humans and other mammals. Since their reemergence in 2003, highly pathogenic avian influenza A (H5N1) viruses have been transmitted from poultry to humans (by direct or indirect contact with infected birds) in several provinces of Mainland China, which has resulted in 22 cases of human infection and has created repercussions for the Chinese economy. People have been concerned whether a new pandemic will occur in the future. The eradication of pathogenic avian influenza viruses appears to be the most effective way to prevent an influenza pandemic. This paper will examine the features of H5N1, including incidence, infection, immunity, clinical management, prevention and control, and therapy in Mainland China. PMID- 17722227 TI - Nanoparticles-a thoracic toxicology perspective. AB - A substantial literature demonstrates that the main ultrafine particles found in ambient urban air are combustion-derived nanoparticles (CDNP) which originate from a number of sources and pose a hazard to the lungs. For CDNP, three properties appear important-surface area, organics and metals. All of these can generate free radicals and so induce oxidative stress and inflammation. Inflammation is a process involved in the diseases exhibited by the individuals susceptible to the effects of PM- development and exacerbations of airways disease and cardiovascular disease. It is therefore possible to implicate CDNP in the common adverse effects of increased PM. The adverse effects of increases in PM on the cardiovascular system are well-documented in the epidemiological literature and, as argued above, these effects are likely to be driven by the combustion-derived NP. The epidemiological findings can be explained in a number of hypotheses regarding the action of NP:-1) Inflammation in the lungs caused by NP causes atheromatous plaque development and destabilization; 2) The inflammation in the lungs causes alteration in the clotting status or fibrinolytic balance favouring thrombogenesis; 3) The NP themselves or metals/organics released by the particles enter the circulation and have direct effects on the endothelium, plaques, the clotting system or the autonomic nervous system/ heart rhythm. Environmental nanoparticles are accidentally produced but they provide a toxicological model for a new class of purposely 'engineered' NP arising from the nanotechnology industry, whose effects are much less understood. Bridging our toxicological knowledge between the environmental nanoparticles and the new engineered nanoparticles is a considerable challenge. PMID- 17722231 TI - Erythema nodosum: clinicopathologic correlations and their use in differential diagnosis. AB - PURPOSE: Typically, a diagnosis of erythema nodosum (EN) is based on clinical features. However, other diseases manifest with inflammatory nodules of the lower limbs in addition to EN, such as the EN-like lesions of Behcet's disease (BD). The purpose of this retrospective study was to investigate the frequency of histologically proven EN among diseases diagnosed clinically as EN, to determine underlying causes of EN, and to compare clinical and histologic features between EN and other diseases. PATIENTS AND METHODS: We selected 99 patients diagnosed clinically with EN and performed skin biopsies. All pathologic slides were evaluated and diagnosed; and after histologic diagnoses were made we reviewed the patients' medical records. RESULTS: Among the 99 patients diagnosed clinically with EN, 47 were biopsy-verified EN. The EN-like lesions of BD and nodular vasculitis were both in the primary differential diagnosis of EN. No definite difference in clinical features exists among these three diseases. Histologically, EN demonstrated septal panniculitis in the majority of patients. Lobular panniculitis was frequently observed in NV, and mixed or mostly lobular panniculitis was observed in the EN-like lesion. Vasculitis was rarely observed in EN; however lymphocytic vasculitis was observed frequently in EN-like lesions and neutrophilic vasculitis was observed in NV. The frequency of granulomatous inflammation was highest in NV. Some cases of patients with typical BD demonstrated classic EN lesions. CONCLUSION: It was extremely difficult to clinically differentiate EN from EN-like lesions or NV. We feel skin biopsy is mandatory for the diagnosis of lower extremity erythematous nodular lesions. PMID- 17722232 TI - DNA polymorphisms and haplotypes of apolipoprotein A5's attribution to the plasma triglyceride levels in Koreans. AB - PURPOSE: Recent studies using human and mice reported that apolipoprotein A-V (APOA5) gene plays an important role in controlling triglyceride (TG) concentrations. The purpose of the present study was to investigate the correlation between single nucleotide polymorphisms (SNPs) and haplotypes in the APOA5 gene and TG in subjects and to search for possible associations of the APOA5 gene variants and common haplotypes with hypertriglyceridemia (HTG). MATERIALS AND METHODS: We examined the case-control subjects including 100 HTG patients and 243 unrelated healthy control. The genes were screened for SNPs by direct sequencing in 48 genetically unrelated individuals. Six SNPs (-1390C>T, 1020G>A, -3A>G, V150M, G182C and 1259T>C) were genotyped in case and control populations. RESULTS: In this study, our results indicated a strong association between APOA5 SNP -3A>G and G182C and elevated TG levels (p<0.001). Analysis of the SNPs from APOA5 gene has identified major haplotype showing very strong association with HTG, CGGGTT (p<0.001). Likelihood ratio test (LRT) of these six SNPs revealed that haplotypes were strong independent predictors of HTG (p<0.001). Haplotype-trend logistic regression (HTR) analysis revealed a significant association between the CGGGGC (haplotype 2) and CGGGTT (haplotype 4) and HTG (OR=2.48, 95% CI=1.06-5.76 and OR=8.54, 95% CI=2.66-27.42, respectively). CONCLUSION: We confirm that the APOA5 variants are associated with triglyceride levels and the haplotype may be strong independent predictors of HTG among Koreans. PMID- 17722233 TI - A comparison of AmBisome to amphotericin B for treatment of systemic candidiasis in very low birth weight infants. AB - PURPOSE: Amphotericin B is considered the treatment of choice for systemic candidiasis, but adverse effects may limit its use. An alternative option for the treatment of candidiasis includes lipid preparations of amphotericin B. This study investigated the safety and efficacy of AmBisome, a lipid formulation of amphotericin B containing liposomal structures, for the treatment of systemic candidiasis in very low birth weight infants (VLBWI). MATERIALS AND METHODS: Data from 26 VLBWI treated with AmBisome in the study group (AmBisome group) from October 2003 to July 2006 were compared with data from 20 VLBWI treated with amphotericin B as a historical control (Amphotericin group). This study was a prospective, historical control, multi-center trial. RESULTS: Candida spp. was isolated in 73% (19/26) of the cases for the AmBisome group and 90% (18/20) of the cases for the Amphotericin group. The fungal eradication rate and the time to eradication was 84% (16/19) and 9+/-8 days in the AmBisome group, and 89% (16/18) and 10+/-9 days in the Amphotericin group, respectively (p=0.680 vs p=0.712). The major adverse effects were lower in the AmBisome group (renal toxicity, 21% vs 55%, p=0.029; hepatotoxity, 25% vs 65%, p=0.014, AmBisome group vs Amphotericin group, respectively). There was no significant difference in mortality attributed to systemic candidiasis (12% in the AmBisome group, 10% in the Amphotericin group, p=0.868). CONCLUSION: AmBisome is effective and safe for treating systemic fungal infections in VLBWI. PMID- 17722234 TI - Comparison of higher-order aberration and contrast sensitivity in monofocal and multifocal intraocular lenses. AB - PURPOSE: The visual performance of pseudophakic eyes depends on the type of intraocular lenses (IOLs) that are implanted. Aspherical and multifocal IOLs have recently been developed to improve visual quality after cataract surgery, but multifocal IOLs can be associated with decreased contrast sensitivity (CS), halos, and glare. This study compares the visual performance of monofocal and multifocal IOLs by measurement of higher-order aberrations (HOAs) and CS values. MATERIALS AND METHODS: HOAs and CS values of 42 eyes with implanted monofocal IOLs and 40 eyes with implanted multifocal IOLs were measured preoperatively and more than 6 months after surgery. In the multifocal IOL group, HOAs and CS values were also measured with addition of a trial lens of -0.5 diopter (D) to evaluate the compensatory effect on spherical aberration. RESULTS: CS values of the multifocal IOL group were significantly lower than those of the monofocal IOL group for all spatial frequencies tested (p<0.01), and the spherical aberration was significantly higher in the multifocal IOL group than in the monofocal IOL group (p<0.001). Addition of a -0.5 D lens to the multifocal IOL group decreased the difference in CS between the two groups (p=0.003). CONCLUSION: Increased spherical aberration may contribute to lower CS in the multifocal IOL group. In such cases, CS can be improved by addition of a -0.5 D lens to compensate for the spherical aberration. PMID- 17722235 TI - Association between internal carotid artery morphometry and posterior communicating artery aneurysm. AB - PURPOSE: The goal of this study was to directly measure the association between the internal carotid artery (ICA) morphometry and the presence of ICA-posterior communicating artery (PCOM) aneurysm. MATERIALS AND METHODS: The authors intraoperatively measured the length of the supraclinoid ICA because it is impossible to radiologically determine the exact location of the anterior clinoid process. We used an image analyzer with a CT angiogram to measure the angle between the skull midline and the terminal segment of the ICA (ICA angle), as well as the diameter of the ICA. The lengths and diameters of the supraclinoid ICA and the ICA angle were compared among PCOM aneurysms, anterior communicating artery (ACOM) aneurysms, and middle cerebral artery (MCA) bifurcation aneurysms (n=27 each). Additionally, the lengths and the diameters of M1 and A1 were compared for each aneurysm. RESULTS: The lengths of the supraclinoid ICA were 11.9+/-2.3 mm. The lengths of the supraclinoid ICA in patients with ICA-PCOM aneurysms (9.7+/-2.8 mm) were shorter than those of patients with ACOM aneurysms (13.8+/-2.2 mm, Student's t-test, p<0.001) and with MCA bifurcation aneurysms (12.2+/-1.9 mm, Student's t-test, p<0.001). The diameters of the supraclinoid ICA and A1 in patients with ACOM aneurysms were larger than those in patients with MCA bifurcation aneurysms (Student's t-test, p<0.05). There were no significant differences in the lengths of M1 and A1, ICA angle, or diameter of M1 for each aneurysm. CONCLUSION: These results suggest that the relatively shorter length of the supraclinoid ICA may be a novel risk factor for the development of ICA-PCOM aneurysm with higher hemodynamic stress. PMID- 17722236 TI - Mid-term results of reconstruction of the right ventricular outflow tract using cryopreserved homografts. AB - PURPOSE: Homograft benefits include excellent hemodynamics, resistance to infection, decreased thromboembolic events, ease of handling, and lack of need for anticoagulation. We examined the short and mid-term results of right ventricular outflow tract (RVOT) reconstruction using cryopreserved homografts. PATIENTS AND METHODS: From May 1998 to May 2005, 20 patients (male:female=10:10) underwent RVOT reconstruction using cryopreserved homografts. The median age was 23.8 years (range, 0.9 to 43.3 years) and the median body weight was 57 kg (range, 7.3 to 80 kg). Eighteen patients underwent re-operation after shunt or corrective operations. Homograft failure was defined as either re-operation for homograft replacement or patient death. Homograft dysfunction was defined as grade 3 or more than 3 of graft regurgitation and more than 40 mmHg of transvalvular pressure gradient under echocardiographic examination. RESULTS: No operative mortality occurred and there were three major complications. Graft failure was observed in one male patient with tetralogy of Fallot. The 8-year freedom from graft failure was 87.5+/-11.7% and the 7-year freedom from graft dysfunction was 62.3+/-17.9%. Multivariable analysis revealed that the independent factor for graft dysfunction was age less than 10 years. In the analysis according to age group, the 7-year freedom from graft dysfunction in the group of patients older than 10 years was 100% and 25.0+/-21.7% in patients age 10 or younger (p= 0.03). CONCLUSION: Right ventricular outflow reconstruction using cryopreserved homografts provided excellent short and mid-term results in most patients in this study. However, in patients younger than 10 years old, homografts for RVOT reconstruction showed a high dysfunction rate at mid-term. PMID- 17722237 TI - The incidence of new vertebral compression fractures in women after kyphoplasty and factors involved. AB - PURPOSE: To identify the incidence of new vertebral compression fractures in women after kyphoplasty and to analyze influential factors in these patients. MATERIALS AND METHODS: One hundred and eleven consecutive female patients with osteoporotic vertebral compression fractures (VCFs) underwent kyphoplasty at 137 levels. These patients were followed for 15.2 months postoperatively. For the survey of new vertebral compression fractures, medical records and x-rays were reviewed, and telephone interviews were conducted with all patients. RESULTS: During that time 20 (18%) patients developed new VCFs. The rate of occurrence of new VCFs in one year was 15.5% using a Kaplan-Meier curve. Body mass index (BMI), symptom duration and kyphoplasty level were the statistically significant factors between the patient groups both with and without new VCFs after kyphoplasty. In the comparison between the adjacent and remote new VCF groups, the adjacent new VCF group showed a larger amount of polymethyl methacrylate (PMMA) use during kyphoplasty (p<0.05). Before kyphoplasty, 9.9% of the patients had been prescribed medication for osteoporosis, and 93.7% of the patients started or continued medication after kyphoplasty. The development of new VCFs was affected by the number of vertebrae involved in the kyphoplasty. However, the lower incidence rate (15.5%) of new compression fractures might be due to a greater percentage (93.7% in our study) of patients taking anti-osteoporotic medication before and/or after kyphoplasty. CONCLUSION: When kyphoplasty is planned for the management of patients with osteoporotic VCFs, the application of a small amount of PMMA can be considered in order to lower the risk of new fractures in adjacent vertebrae. The postoperative use of anti- osteoporotic medication is recommended for the prevention of new VCFs. PMID- 17722239 TI - The effects of melatonin on postoperative intraabdominal adhesion formation. AB - PURPOSE: Postoperative intraabdominal adhesion formation is a major clinical problem. No previous study was found, reporting the relationship between adhesion formation and melatonin administration, but melatonin, a strong antioxidant, is recognized to have certain effects on the progression of adhesion formation mechanism. It was therefore decided to investigate the effects of melatonin on postoperative adhesion formation. MATERIALS AND METHODS: A total number of 24 Sprague-Dawley rats were utilized. Three groups, described as: Group A, sham laparatomy (n=8), Group B, rats that underwent only ischemia-reperfusion (n=8) and Group C, rats that underwent ischemia- reperfusion and were given 10 mg/kg melatonin solution i.v. (n=8). For Groups B and C, the ileocolic vessels were clamped. Blood glutathione peroxidase levels of all study groups were assessed, then microscopic and macroscopic adhesion scores were evaluated. RESULTS: Glutathione peroxidase levels of the melatonin-treated group were significantly higher and fibroblast proliferation and macroscopic adhesion scores were significantly lower, than in the melatonin-free group. CONCLUSION: The results of this study supported the hypothesis, that melatonin administration may prevent intraabdominal adhesions resulting from surgery. PMID- 17722238 TI - High concentrations of pamidronate in bone weaken the mechanical properties of intact femora in a rat model. AB - PURPOSE: Bisphosphonates have been used to treat osteoporosis for more than ten years. However, complications associated with long-term administration of bisphosphonates, such as nonunion after pelvic insufficiency fracture or osteonecrosis of the jaw, have been recently reported in the literature. We investigated the relationships among the mechanical properties of the intact rat femur as well as healing fracture calluses and the intraosseous concentration of pamidronate (ICP), after long-term administration of pamidronate in a rat osteoporosis model. MATERIALS AND METHODS: We performed bilateral ovariectomy in 25 3-month-old female Sprague-Dawley rats. Beginning three months after ovariectomy, disodium pamidronate (0.5 mg/kg) was injected every month. After the six-month administration period, the left femoral shaft was fractured using the closed fracture technique. Five weeks after fracture, 23 rats were euthanized and both femora were removed. We checked the mechanical properties of the intact (right) and fractured (left) femora using a three-point bending technique. Intraosseous concentration of pamidronate was checked by high-performance liquid chromatography. RESULTS: The mean ICP was 61.8+/-15.7 ng/mg of bone. High ICP decreased the ultimate load to failure, stiffness, and ultimate stress of the intact femora (p=0.015, 0.027, 0.039, respectively). There was a tendency to decrease the ultimate load to failure in the healing callus when the ICP increased (p= 0.183). High ICP decreased the bone mineral density of the femoral head (p=0.005). CONCLUSION: High concentrations of pamidronate in intact bone decreased the bone mineral density and weakened the mechanical strength of the rat femora. The mechanical strength of the early healing callus was not correlated with concentration of pamidronate in the bone. PMID- 17722240 TI - Diurnal variation of pulse wave velocity assessed non-invasively by applanation tonometry in young healthy men. AB - PURPOSE: Pulse wave velocity (PWV) is at least partially controlled by vascular tone. Vascular tone and underlying physiological processes such as sympathetic activity, plasma catecholamin, and cortisol levels have been shown to follow diurnal variations. MATERIALS AND METHODS: Carotid-to-radial PWV was non invasively assessed by applanation tonometry in 21 young (26.5+/-2.3 years) healthy men at three different time points (8:00 hr, 12:00 hr, 17:00 hr) during a day. Additionally, heart rate, systolic, diastolic and mean blood pressure, and radial pulse pressure were assessed at the same time points. RESULTS: The mean PWV was significantly higher at 8:00 hr compared with the mean PWV assessed at later time points. No significant differences were found between mean PWV at 12:00 hr and at 17:00 hr. When PWV was corrected for blood pressure, the difference between values at 8:00 hr and 12:00 hr was no longer significant. Systolic, diastolic and mean blood pressure were significantly lower at 17:00 hr compared with those at 8:00 hr. CONCLUSION: A small but significant diurnal variation of PWV was observed in young healthy men, which might have been caused at least partly by variations of blood pressure. This finding could be of value, when PWV is used in human research. Thus, in longitudinal investigations the measurements should be performed at similar time points in the course of a day, in order to obtain comparable data. Additionally, our observations ought to be of assistance to studies in which novel pharmacological compounds with activity on the vasculature are investigated. PMID- 17722241 TI - The usefulness of fetal MRI for prenatal diagnosis. AB - PURPOSE: Fast MRI has provided detailed and reproducible fetal anatomy. This study was performed to evaluate the usefulness of fetal MRI for prenatal diagnosis. MATERIALS AND METHODS: Fifty-six fetuses with congenital abnormalities on ultrasonography were evaluated by fetal MRI from 2001 to 2004 in Severance Hospital. Final diagnosis was made by postnatal pathology, postnatal MRI, and other modalities (such as ultrasound, retrograde pyelogram). A 1.5-Tesla superconductive MR imaging unit was used to obtain half-Fourier acquisition single-shot turbo spin images. RESULTS: Of the 56 fetuses, intracranial abnormalities were found in 26 fetuses, intraabdominal abnormalities in 17 fetuses, intrathoracic in 6 fetuses, head and neck in 5 fetuses, and other sites in 2 fetuses. There were six cases in which the diagnoses of fetal MRI and ultrasonography differed. In such cases, fetal MRI provided more exact diagnosis than ultrasonography (5 vs. 0). Three fetuses with intracranial abnormalities on ultrasonography were diagnosed as normal by fetal MRI and in postnatal diagnosis. CONCLUSION: Although ultrasonography is known as a screening modality of choice in the evaluation of fetus because of the cost-effectiveness and safety, the sonographic findings are occasionally inconclusive or insufficient for choosing the proper management. Thus, in this study, we suggest that fetal MRI is more useful than ultrasonography for the evaluation of intracranial abnormalities in some instances. For prenatal counseling and postnatal treatment planning, fetal MRI can be informative when prenatal ultrasonography is inadequate and doubtful. PMID- 17722242 TI - Accuracy of a high prostate-specific antigen level for prostate cancer diagnosis upon initial biopsy in Korean men. AB - PURPOSE: This study aimed to evaluate the cancer detection rate in a Korean population with prostate-specific antigen (PSA) levels greater than or equal to 20.0 ng/mL. MATERIALS AND METHODS: A total of 174 men 50 to 79 years old (median 69) included in the study. The median prostate volume of the patients was 44.8 mL (range 14.1 to 210.0) and their serum PSA ranged from 20.0 to 9725.0 ng/mL (median 44.8). RESULTS: Of 174 men 141 (81.0%) were diagnosed with prostate cancer on initial biopsy. In the total number of patients, the positive predictive value (PPV) was 62.9% for PSA 20 to 29.9, 72.7% for PSA 30 to 39.9 and 100% for PSA 40 to 49.9 ng/mL. In patients with an abnormal digital rectal examination (DRE), the values for these PSA ranges increased to 89.5%, 91.7% and 100%, respectively. The PPV was 81.0% for PSA cutoff of 20, 89.2% for a cutoff of 30, 95.4% for a cutoff of 40, and 94.7% for a cutoff of 50 ng/mL. In conjunction with an abnormal DRE, the values for these PSA cutoffs increased to 95.9%, 98.1%, 100%, and 100%, respectively. CONCLUSION: Our data suggest the ability to predict the presence of prostate cancer reliably on initial biopsy when PSA threshold is greater than or equal to 50 ng/mL. This PSA threshold may be lowered to 40 ng/mL in the presence of an abnormal DRE. In Korean men with high PSA, the detection rate of prostate cancer on biopsy appears to be comparable to that for American men. PMID- 17722243 TI - Heterogeneous composition of voltage-dependent K(+) currents in hepatic stellate cells. AB - PURPOSE: Hepatic stellate cells (HSC) are a type of pericyte with varying characteristics according to their location. However, the electrophysiological properties of HSC are not completely understood. Therefore, this study investigated the difference in the voltage-dependent K(+) currents in HSC. MATERIALS AND METHODS: The voltage-dependent K(+) currents in rat HSC were evaluated using the whole cell configuration of the patch-clamp technique. RESULTS: Four different types of voltage-dependent K(+) currents in HSC were identified based on the outward and inward K(+) currents. Type D had the dominant delayed rectifier K(+) current, and type A had the dominant transient outward K(+) current. Type I had an inwardly rectifying K(+) current, whereas the non type I did not. TEA (5 mM) and 4-AP (2 mM) suppressed the outward K(+) currents differentially in type D and A. Changing the holding potential from -80 to -40 mV reduced the amplitude of the transient outward K(+) currents in type A. The inwardly rectifying K(+) currents either declined markedly or were sustained in type I during the hyperpolarizing step pulses from -120 to -150 mV. CONCLUSION: There are four different configurations of voltage-dependent K(+) currents expressed in cultured HSC. These results are expected to provide information that will help determine the properties of the K(+) currents in HSC as well as the different type HSC populations. PMID- 17722245 TI - A case of adult polyglucosan body disease. AB - Adult polyglucosan body disease (APBD) is a rare neurological disease, characterized by adult onset (fifth to seventh decades), progressive sensorimotor or pure motor peripheral neuropathy, upper motor neuron symptoms, neurogenic bladder, and cognitive impairment. APBD is confirmed by a sural nerve biopsy that shows the widespread presence of polyglucosan bodies in the nerve. We report a 70 year old male patient who exhibited progressive weakness in all extremities and dementia. His electrodiagnostic studies showed sensorimotor polyneuropathy and muscle pathology that consisted of polyglucosan bodies located in small peripheral nerves. This is the first case of APBD reported in Korea. PMID- 17722244 TI - Prognostic implications of cyclin B1, p34cdc2, p27(Kip1) and p53 expression in gastric cancer. AB - PURPOSE: Cell cycle progression is regulated by interactions of specific cyclins and cyclin dependent kinases (CDKs) at the G1-S and G2-M checkpoints and cell cycle deregulation plays a major role in carcinogenesis of human cancers. PATIENTS AND METHODS: To investigate the role of cell cycle regulators in the pathogenesis and progression of human gastric cancers, 23 cases of gastric carcinomas were examined for the expression of cyclin B1, p34cdc2, p27(Kip1) and p53 by immunohistochemical methods, and gene expression was correlated with various clinicopathologic findings. RESULTS: Out of 23 cases studied, cyclin B1 was diffusely expressed in 20 cases (87.0%), p34cdc2 in 14 cases (60.9%) and p53 in 12 cases (52.2%), whereas in normal gastric tissues, cyclin B1 and p34cdc2 were weakly expressed and p53 was not expressed. In contrast, p27(Kip1) was expressed in only 8.7% of gastric carcinomas compared with 78.3% of normal gastric tissues. There was correlation between the expression of cyclin B1 and expression of p34cdc2 (p=0.002), between the expression of cyclin B1 and loss of p27(Kip1) (p=0.025), and between the expression of p34cdc2 and loss of p27(Kip1) (p=0.065). In addition, expression of cyclin B1 was correlated with regional lymph node metastasis (p=0.032). CONCLUSION: Our results indicate that cyclin B1 and p34cdc2 are involved in the genesis or progression of gastric cancers. Furthermore, overexpression of cyclin B1 may play an important role in lymph node metastatic potential of gastric cancer. Thus, abnormal expression of cyclin B1 and CDKs, overexpression of p53 and loss of p27(Kip1) expression may play important roles in human gastric carcinogenesis. PMID- 17722246 TI - Congenital cavernous sinus cystic teratoma. AB - Teratomas represent 0.5% of all intracranial tumors. These benign tumors contain tissue representative of the three germinal layers. Most teratomas are midline tumors located predominantly in the sellar and pineal regions. The presence of a teratoma in the cavernous sinus is very rare. Congenital teratomas are also rare, especially those of a cystic nature. To our knowledge, this would be the first case report of a congenital, rapidly growing cystic teratoma within the cavernous sinus. A three-month-old boy presented with a past medical history of easy irritability and poor oral intake. A magnetic resonance image (MRI) scan of the head disclosed a large expanding cystic tumor filling the right cavernous sinus and extending into the pterygopalatine fossa through the foramen rotunda. These scans also demonstrated a small area of mixed signal intensity, the result of the different tissue types conforming to the tumor. Heterogeneous enhancement was seen after the infusion of contrast medium. However, this was a cystic tumor with a large cystic portion. Thus, a presumptive diagnosis of cystic glioma was made. With the use of a right frontotemporal approach, extradural dissection of the tumor was performed. The lesion entirely occupied the cavernous sinus, medially displacing the Gasserian ganglion and trigeminal branches (predominantly V1 and V2). The lesion was composed of different tissues, including fat, muscle and mature, brain-like tissue. The tumor was completely removed, and the pathological report confirmed the diagnosis of a mature teratoma. There was no evidence of recurrence. Despite the location of the lesion in the cavernous sinus, total removal can be achieved with the use of standard microsurgical techniques. PMID- 17722247 TI - Paraspinal abscess communicated with epidural abscess after extra-articular facet joint injection. AB - Facet joint injection is considered to be a safe procedure. There have been some reported cases of facet joint pyogenic infection and also 3 cases of facet joint infection spreading to paraspinal muscle and epidural space due to intra articular injections. To the author's knowledge, paraspinal and epidural abscesses after facet joint injection without facet joint pyogenic infection have not been reported. Here we report a case in which extra-articular facet joint injection resulted in paraspinal and epidural abscesses without facet joint infection. A 50-year-old man presenting with acute back pain and fever was admitted to the hospital. He had the history of diabetes mellitus and had undergone the extra-articular facet joint injection due to a facet joint syndrome diagnosis at a private clinic 5 days earlier. Physical examination showed tenderness over the paraspinal region. Magnetic resonance image (MRI) demonstrated the paraspinal abscess around the fourth and fifth spinous processes with an additional epidural abscess compressing the thecal sac. The facet joints were preserved. The laboratory results showed a white blood cell count of 14.9 x 10(9) per liter, an erythrocyte sedimentation rate of 52 mm/hour, and 10.88 mg/dL of C-reactive protein. Laminectomy and drainage were performed. The pus was found in the paraspinal muscles, which was communicated with the epidural space through a hole in the ligamentum flavum. Cultures grew Staphylococcus aureus. Paraspinal abscess communicated with epidural abscess is a rare complication of extra articular facet joint injection demonstrating an abscess formation after an invasive procedure near the spine is highly possible. PMID- 17722248 TI - Spontaneous regression of a cystic tumor in a postpartum woman; is it a cystic lymphangioma? AB - Spontaneous regression of intra-abdominal cystic tumors in adults is unusual. Here, we present the case of an apparently spontaneous regression of a large intra-abdominal cystic mass found in the postpartum period of an 18-year-old woman. The regression was demonstrated using serial computed tomography (CT) examinations over a two-year period. PMID- 17722249 TI - Multi-disciplinary treatment of a rare pelvic cavity ependymoma. AB - Ependymomas usually develop from neuroectodermal organs. Here, we present an ependymoma arising from the pelvic cavity. A 27-year-old Korean female was admitted to the hospital with a sensation of abdominal fullness. Imaging studies revealed a huge heterogeneous nodular mass in the pelvis and lower abdomen. Laparotomy showed that two large masses with multiple nodules were located between the uterus and rectum and uterus and bladder, respectively. Histologically, the tumor was characterized by compact columnar neoplastic cells divided by fibrovascular septae. The neoplastic cells formed true ependymal rosettes and perivascular pseudorosettes. Immunohistochemical staining showed a strong positive reaction for glial fibrillary acidic protein (GFAP) and vimentin and a partial positive reaction for S100 and EMA. The tumor was thus diagnosed as an ependymoma arising from the pelvic cavity. The patient was treated with a debulking operation and chemotherapy based upon the in vitro chemosensitivity test results. The patient was free of cancer for 4 years following surgery. This is a rare case of extraneural ependymoma for which an in vitro chemosensitivity test was critical in determining the multidisciplinary approach for treatment. PMID- 17722250 TI - Penoscrotal reconstruction using groin and bilateral superomedial thigh flaps: a case of penile vaselinoma causing Fournier's gangrene. AB - Penile augmentation by the injection of mineral oil provokes many serious, undesirable effects. Although there are reports of complications such as deformity, ulceration, necrosis, and erectile dysfunction, Fournier's gangrene resulting from the injection of petroleum jelly into the penis has not been reported. Here, we present a 42-year-old man with penile vaselinoma causing Fournier's gangrene which was treated successfully with aggressive surgical debridement, followed by penoscrotal reconstruction using groin and bilateral superomedial thigh flaps. PMID- 17722251 TI - Granular cell tumors of the abdominal wall. AB - Granular cell tumors (GCT) are found in virtually any body site, including the tongue, skin, subcutaneous tissue, breast, rectum and vulva. However, they are rarely seen in the abdominal wall. We report here on a rare case of GCT in the rectus muscle of the abdominal wall. A 44-year-old woman presented with a non tender, hard mass in the right lower abdominal wall. Upon microscopic examination, the tumor was found to comprise of large polygonal cells with an abundant eosinophilic granular cytoplasm and round to oval nuclei. Upon immunohistochemical staining, the large cells showed S-100 and CD68 positive granular aggregates in the cytoplasm. Many lysosomes of variable size were observed in the cytoplasm. PMID- 17722252 TI - Trials begin on HIV gel for women. PMID- 17722253 TI - Ask the doctor. Do beta blockers and ACE inhibitors help or harm the heart? PMID- 17722254 TI - By the way, doctor. I heard about a new test for prostate cancer that's better than the PSA test. Should I get this test? PMID- 17722256 TI - Findings of misconduct in science. PMID- 17722257 TI - Welcome to the international journey to improving human health. PMID- 17722255 TI - Hyposmotic stimulation-induced nitric oxide production in outer hair cells of the guinea pig cochlea. AB - Nitric oxide (NO) production during hyposmotic stimulation in outer hair cells (OHCs) of the guinea pig cochlea was investigated using the NO sensitive dye DAF 2. Simultaneous measurement of the cell length and NO production showed rapid hyposmotic-induced cell swelling to precede NO production in OHCs. Hyposmotic stimulation failed to induce NO production in the Ca2+-free solution. L-NG nitroarginine methyl ester (L-NAME), a non-specific NO synthase inhibitor and gadolinium, a stretch-activated channel blocker inhibited the hyposmotic stimulation-induced NO production whereas suramin, a P2 receptor antagonist did not. S-nitroso-N-acetylpenicillamine (SNAP), a NO donor inhibited the hyposmotic stimulation-induced increase in the intracellular Ca2+ concentrations ([Ca2+]i) while L-NAME enhanced it. 1H-[1,2,4]oxadiazole[4,3a]quinoxalin-1-one, an inhibitor of guanylate cyclase and KT5823, an inhibitor of cGMP-dependent protein kinase (PKG) mimicked effects of L-NAME on the Ca2+ response. Transient receptor potential vanilloid 4 (TRPV4), an osmo- and mechanosensitive channel was expressed in the OHCs by means of immunohistochemistry. 4alpha-phorbol 12,13 didecanoate, a TRPV4 synthetic activator, induced NO production in OHCs. These results suggest that hyposmotic stimulation can induce NO production by the [Ca2+]i increase, which is presumably mediated by the activation of TRPV4 in OHCs. NO conversely inhibits the Ca2+ response via the NO-cGMP-PKG pathway by a feedback mechanism. PMID- 17722258 TI - Micro- and nanotechnology in cell separation. AB - This review describes recent work in cell separation using micro- and nanoscale technologies. These devices offer several advantages over conventional, macroscale separation systems in terms of sample volumes, low cost, portability, and potential for integration with other analytical techniques. More importantly, and in the context of modern medicine, these technologies provide tools for point of-care diagnostics, drug discovery, and chemical or biological agent detection. This review describes work in five broad categories of cell separation based on (1) size, (2) magnetic attraction, (3) fluorescence, (4) adhesion to surfaces, and (5) new emerging technologies. The examples in each category were selected to illustrate separation principles and technical solutions as well as challenges facing this rapidly emerging field. PMID- 17722259 TI - Nanofibers and their applications in tissue engineering. AB - Developing scaffolds that mimic the architecture of tissue at the nanoscale is one of the major challenges in the field of tissue engineering. The development of nanofibers has greatly enhanced the scope for fabricating scaffolds that can potentially meet this challenge. Currently, there are three techniques available for the synthesis of nanofibers: electrospinning, self-assembly, and phase separation. Of these techniques, electrospinning is the most widely studied technique and has also demonstrated the most promising results in terms of tissue engineering applications. The availability of a wide range of natural and synthetic biomaterials has broadened the scope for development of nanofibrous scaffolds, especially using the electrospinning technique. The three dimensional synthetic biodegradable scaffolds designed using nanofibers serve as an excellent framework for cell adhesion, proliferation, and differentiation. Therefore, nanofibers, irrespective of their method of synthesis, have been used as scaffolds for musculoskeletal tissue engineering (including bone, cartilage, ligament, and skeletal muscle), skin tissue engineering, vascular tissue engineering, neural tissue engineering, and as carriers for the controlled delivery of drugs, proteins, and DNA. This review summarizes the currently available techniques for nanofiber synthesis and discusses the use of nanofibers in tissue engineering and drug delivery applications. PMID- 17722261 TI - Increased endothelial and vascular smooth muscle cell adhesion on nanostructured titanium and CoCrMo. AB - In the body, vascular cells continuously interact with tissues that possess nanostructured surface features due to the presence of proteins (such as collagen and elastin) embedded in the vascular wall. Despite this fact, vascular stents intended to restore blood flow do not have nanoscale surface features but rather are smooth at the nanoscale. As the first step towards creating the next generation of vascular stent materials, the objective of this in vitro study was to investigate vascular cell (specifically, endothelial, and vascular smooth muscle cell) adhesion on nanostructured compared with conventional commercially pure (cp) Ti and CoCrMo. Nanostructured cp Ti and CoCrMo compacts were created by separately utilizing either constituent cp Ti or CoCrMo nanoparticles as opposed to conventional micron-sized particles. Results of this study showed for the first time increased endothelial and vascular smooth muscle cell adhesion on nanostructured compared with conventional cp Ti and CoCrMo after 4 hours' adhesion. Moreover, compared with their respective conventional counterparts, the ratio of endothelial to vascular smooth muscle cells increased on nanostructured cp Ti and CoCrMo. In addition, endothelial and vascular smooth muscle cells had a better spread morphology on the nanostructured metals compared with conventional metals. Overall, vascular cell adhesion was better on CoCrMo than on cp Ti. Results of surface characterization studies demonstrated similar chemistry but significantly greater root-mean-square (rms) surface roughness as measured by atomic force microscopy (AFM) for nanostructured compared with respective conventional metals. For these reasons, results from the present in vitro study provided evidence that vascular stents composed of nanometer compared with micron sized metal particles (specifically, either cp Ti or CoCrMo) may invoke cellular responses promising for improved vascular stent applications. PMID- 17722260 TI - Polydisulfide Gd(III) chelates as biodegradable macromolecular magnetic resonance imaging contrast agents. AB - Macromolecular gadolinium (Gd)(III) complexes have a prolonged blood circulation time and can preferentially accumulate in solid tumors, depending on the tumor blood vessel hyperpermeability, resulting in superior contrast enhancement in magnetic resonance (MR) cardiovascular imaging and cancer imaging as shown in animal models. Unfortunately, safety concerns related to these agents' slow elimination from the body impede their clinical development. Polydisulfide Gd(III) complexes have been designed and developed as biodegradable macromolecular magnetic resonance imaging (MRI) contrast agents to facilitate the clearance of Gd(III) complexes from the body after MRI examinations. These novel agents can act as macromolecular contrast agents for in vivo imaging and excrete rapidly as low-molecular-weight agents. The rationale and recent development of the novel biodegradable contrast agents are reviewed here. Polydisulfide Gd(III) complexes have relatively long blood circulation time and gradually degrade into small Gd(III) complexes, which are rapidly excreted via renal filtration. These agents result in effective and prolonged in vivo contrast enhancement in the blood pool and tumor tissue in animal models, yet demonstrate minimal Gd(III) tissue retention as the clinically used low-molecular-weight agents. Structural modification of the agents can readily alter the contrast-enhancement kinetics. Polydisulfide Gd(III) complexes are promising for further clinical development as safe, effective, biodegradable macromolecular MRI contrast agents for cardiovascular and cancer imaging, and for evaluation of therapeutic response. PMID- 17722262 TI - Incorporation of quantum dots on virus in polycationic solution. AB - Developing methods to label viruses with fluorescent moieties has its merits in elucidating viral infection mechanisms and exploring novel antiviral therapeutics. Fluorescent quantum dots (QDs), an emerging probe for biological imaging and medical diagnostics, were employed in this study to tag retrovirus encoding enhanced green fluorescent protein (EGFP) genes. Electrostatic repulsion forces generated from both negatively charged retrovirus and QDs were neutralized by cationic Polybrene, forming colloidal complexes of QDs-virus. By examining the level of EGFP expression in 3T3 fibroblast cells treated with QDs-tagged retroviruses for 24 hours, the infectivity of retrovirus incorporated with QDs was shown to be only slightly decreased. Moreover, the imaging of QDs can be detected in the cellular milieu. In summary, the mild method developed here makes QDs-tagged virus a potential imaging probe for direct tracking the infection process and monitoring distribution of viral particles in infected cells. PMID- 17722263 TI - Selective adhesion and mineral deposition by osteoblasts on carbon nanofiber patterns. AB - In an effort to develop better orthopedic implants, osteoblast (bone-forming cells) adhesion was determined on microscale patterns (30 microm lines) of carbon nanofibers placed on polymer substrates. Patterns of carbon nanofibers (CNFs) on a model polymer (polycarbonate urethane [PCU]) were developed using an imprinting method that placed CNFs in selected regions. Results showed the selective adhesion and alignment of osteoblasts on CNF patterns placed on PCU. Results also showed greater attraction forces between fibronectin and CNF (compared with PCU) patterns using atomic force microscope force-displacement curves. Because fibronectin is a protein that mediates osteoblast adhesion, these results provide a mechanism of why osteoblast adhesion was directed towards CNF patterns. Lastly, this study showed that the directed osteoblast adhesion on CNF patterns translated to enhanced calcium phosphate mineral deposition along linear patterns of CNFs on PCU. Since CNFs are conductive materials, this study formulated substrates that through electrical stimulation could be used in future investigations to further promote osteoblasts to deposit anisotropic patterns of calcium-containing mineral similar to that observed in long bones. PMID- 17722264 TI - Nanopillar array structures for enhancing biosensing performance. AB - Fabrication of metallic nanopillar array structures and their application as electrodes in electrochemical-based biosensors are discussed in this report. Vertically standing nanopillar array structures were fabricated using an electrodeposition technique and their electrochemical characteristics were evaluated. For possible use in biosensing applications, these standing nanopillars should have sufficient mechanical stability to sustain the capillary forces caused by the nanopillar-liquid interactions in aqueous environment and should provide increased signal response in an electrochemical process. Our results showed that the developed nanopillar arrays were mechanically stable in aqueous environments and the nanostructured electrodes exhibited increased electrochemical response compared with flat electrodes. PMID- 17722265 TI - Silk-fibroin-coated liposomes for long-term and targeted drug delivery. AB - Many barriers to drug delivery into a tumor site require careful consideration when designing a new drug. In this study, the adhesive targeting and drug specificity of modified liposomal vesicles on human-scar-producing cells, keloid fibroblasts, were investigated. Keloids express abundant levels of mucopolysaccharides and receptor tyrosine kinase (RTK). In this report, the structural properties, drug release kinetics, and therapeutic availability of silk-fibroin-coated, emodin-loaded liposomes (SF-ELP), compared with uncoated, emodin-loaded liposomes (ELP), were investigated. SF-ELP had a highly organized lamellae structure, which contributed to 55% of the liposomal diameter. This modified liposomal structure decreased emodin release rates by changing the release kinetics from a swelling and diffusional process to a purely diffusional process, probably due to steric hindrance. SF-ELP also increased adhesion targeting to keloid fibroblasts. Increased retention of SF-ELP is most likely due to the interaction of the fibrous protein coating around the ELP with the pericellular molecules around the cell. SF-ELP also decreased survival rate of keloids that expressed high levels of RTK. These results demonstrated that SF-ELP enhanced emodin delivery by improved diffusion kinetics and specific cell targeting. PMID- 17722266 TI - On the way to building an integrated computational environment for the study of developmental patterns and genetic diseases. AB - Genetic diseases and developmental patterns should be studied on several levels: from macroscale (organs and tissues) to nanoscale (cells, genes, proteins). Due to the overwhelming complexity of the life science data, it is common that disparate data pieces are meticulously stored but never fully analyzed or correlated. We have begun to develop a novel methodology based on virtual reality techniques for the study of these phenomena. Our key approach to knowledge integration is a top-down mapping of data onto visual contexts. For each organism that we want to study, a structural model is created and used as a visual "wireframe" onto which other data types are superimposed in a top-down assembly. Data analysis tools, visual controls, and queries are enabled so that users can interactively explore data. Our visualization technology gives users an opportunity to map disparate data onto a common model, and search visually for hitherto unknown patterns and correlations contained within the data. It is our goal to eventually transform genomics research from measuring various data pieces analytically into a fully interactive exploration of combined data in a 4D immersive visual environment that best matches a researcher's intuition. PMID- 17722267 TI - Peptide crosslinked micelles: a new strategy for the design and synthesis of peptide vaccines. AB - This report presents a new and simple methodology for the synthesis of multicomponent peptide vaccines, named the peptide crosslinked micelles (PCMs). The PCMs are core shell micelles designed to deliver peptide antigens and immunostimulatory DNA to antigen-presenting cells (APCs). They are composed of immunostimulatory DNA, peptide antigen, and a thiopyridal derived poly(ethylene glycol)-polylysine block copolymer. The peptide antigen acts as a crosslinker in the PCM strategy, which allows the peptide antigen to be efficiently encapsulated into the PCMs and also stabilizes them against degradation by serum components. Cell culture studies demonstrated that the PCMs greatly enhance the uptake of peptide antigens into human dendritic cells. PMID- 17722268 TI - Tertiary structural analysis of the elongated part of an abnormal hemoglobin, hemoglobin Pakse. AB - Hemoglobin variants in which a frameshift results in chain elongation are unusual. Hemoglobin Pakse (Hb Pakse) is an unstable hemoglobin with abnormal elongation, first described in Indochina. An alpha2-globin gene termination codon mutation, TAA -->TAT or Term -->Tyr, has been described in the pathogenesis of Hb Pakse. This abnormality causes a frameshift that elongates the alpha chain amino acids. Computer-based protein structure modeling was used in a bioinformatics analysis of the tertiary structure of these elongated amino acid sequences. The elongated part of Hb Pakse showed additional helices, which may cause the main alteration in Hb Pakse. Abnormalities in the fold structure of globin in Hb Pakse were identified, and helices additional to the normal alpha globin chains were shown in the elongated part of Hb Pakse. PMID- 17722269 TI - Where is the weak linkage in the globin chain? AB - Hemoglobinopathies are important inherited disorders with high prevalence in many tropical countries. Prediction of protein nanostructure and function is a great challenge in proteomics and structural genomics. Identifying the point vulnerable to mutation is a new trend in research on disorders at the genomic and proteomic level. A bioinformatics analysis was performed to determine the positions that tend to correspond with peptide motifs in the amino acid sequence of alpha and beta globin chains. To identify the weak linkage in alpha globin and beta globin chains, a new bioinformatics tool, GlobPlot, was used. For the alpha globin chain, 22 positions were identified: the disorders were found at positions 3-8, 38-42, 46-51, and 75-79. For the beta globin chain, 46 positions were identified: the disorders were found at positions 61-146. The study showed that weak linkages in alpha globin and beta globin chains can be identified and provide good information for predicting possible new mutations that could lead to new hemoglobinopathies. PMID- 17722270 TI - Quantum chemical analysis of the deferiprone-iron binding reaction. AB - To prevent side effects of excessive accumulation of iron in the body, chelation therapy is recommended in transfusion-dependent patients. The reaction between deferiprone and iron to form a complex red substance can be described as 3 molecules of the chelator, deferiprone, reacting with a molecule of iron. However, the actual mechanism of the deferiprone-iron binding reaction is not well understood. A quantum chemical analysis of the deferiprone-iron binding reaction was performed, focusing on the reaction between 1 molecule of deferiprone and I molecule of iron. The two main alternative pathways for the deferiprone-iron binding reaction were shown to be C-C cleavage and C-O cleavage. The required energy for complex formation in C-C cleavage was less than for C-O cleavage. The total energy requirement for C-C cleavage was negative, implying that this reaction can occur without any external energy source. The resulting complex fits the reported tertiary structure model for the deferiprone-iron complex. PMID- 17722271 TI - Nanomedicine: real commercial potential or just hype? PMID- 17722272 TI - Biological and clinical characterization of paclitaxel poliglumex (PPX, CT-2103), a macromolecular polymer-drug conjugate. AB - Paclitaxel is a widely used chemotherapeutic agent; however, its therapeutic index is limited by low tumor exposure and high systemic exposure. Paclitaxel poliglumex (PPX) is macromolecular drug conjugate that links paclitaxel with a biodegradable polymer, poly-L-glutamic acid. PPX enhances tumor exposure by taking advantage of the hyperpermeable vasculature and suppressed lymphatic clearance characteristic of tumor tissue. The release of paclitaxel from the polymeric backbone is, at least in part, dependent on the metabolism of PPX by the lysosomal protease cathepsin B, which is upregulated in many tumor types. Retrospective analysis of clinical data from two phase III trials in advanced lung cancer suggests that PPX activity may be modulated by estradiol: a trend toward improved survival in the PPX arm compared with the control arm was observed in female, but not in male patients. Estrogens are known to induce cathepsin B activity; cathepsin B-mediated proteolysis is a key enzymatic processing step in PPX metabolism. The association between estrogens and PPX activity is being further explored in ongoing preclinical studies. An additional phase III trial will enroll women with advanced NSCLC to prospectively evaluate the efficacy of PPX in relation to pre- and post-menopausal estrogen levels. PMID- 17722273 TI - Nanomedicines in the treatment of acromegaly: focus on pegvisomant. AB - This article examines the role of pegvisomant in the treatment of acromegaly. This syndrome, caused by excessive growth hormone (GH) secretion by a pituitary adenoma, is associated with a doubled mortality rate and poor quality of life. Pituitary microsurgery has long been the first choice of treatment since it cures many patients, especially those with localized tumors. Adjuvant irradiation was given if insulin-like growth factor-I (IGF-I) or GH did not normalize. The introduction of long-acting slow- release somatostatin analogs was a breakthrough for adjuvant treatment, although not always effective. Rather, targeting excessive GH production, muting the GH signal at its receptor, was a totally different approach. The development of GH antagonists (by mutation ofglycine at position 120) and other modifications to enhance receptor binding, and subsequent pegylation of the molecule led to the development of B2036. After pegylation of B2036 at 5 positions the distribution volume is restricted and its serum half life considerably increased. In short-term clinical studies performed in selected, mostly pretreated, acromegalic patients, IGF-I normalized in the majority of cases. Combination therapy with long-acting somatostatin analogs and weekly rather than daily pegvisomant injections appears to be successful in one clinical study and might limit the high cost of pegvisomant. Long-term efficacy and safety has to be demonstrated. The drug does not cross the blood-brain barrier, and whether it distributes freely into the extracellular space of other organs than the liver has not been investigated, which might have implications for persistent local IGF-I production under unrestrained GH concentrations. PMID- 17722274 TI - Nanomedicines in the treatment of patients with hepatitis C co-infected with HIV- focus on pegylated interferon-alpha. AB - In immuno-competent individuals, the natural course of chronic hepatitis C virus (HCV) infection is highly variable and 5%-30% of patients develop cirrhosis over 20 years. Co-infection with HCV and human immunodeficiency virus (HIV) is an important prognostic factor and associated with more frequent and accelerated progression to cirrhosis. Until recently HIV/AIDS-related complications were life limiting in patients co-infected with HCV; the introduction of highly active antiretroviral treatment (HAART) and the better prognosis of HIV infection has made HCV-related complications an emerging health problem in HCV/HIV coinfected individuals. Treatment of chronic HCV infection has also evolved since the introduction of interferon-alpha. Recently, introduction of pegylated interferon alpha (peginterferon-alpha) has resulted in an increase in sustained virus clearance rates of up to 80% in selected genotypes and patient populations. The safety and efficacy of modern anti HCV treatment regimens - based on peginterferon-alpha in combination with ribavirin - was evaluated in 4 controlled trials. Sustained clearance of hepatitis C virus can be achieved in up to 35% of patients with HIV/HCV co-infection, and novel HCV treatment regimens based on peginterferon-alpha have no negative effect on the control of HIV disease. In conclusion, if HIV infection is well controlled and CD4+ cell counts >100/mm3, treatment of chronic hepatitis C with peginterferon in combination with ribavirin is safe and should be given for 48 weeks regardless of the HCV genotype. Introduction of peginterferon-alpha has significantly improved adherence to treatment and treatment efficacy; in particular sustained virologic response in patients with HCV genotype 1 or 4 infection improved, but sustained viral clearance in only 7%-38% of patients infected with genotype I and 4 cannot be the final step in development of effective treatments in patients with HCV/HIV co infection. PMID- 17722275 TI - Megestrol acetate in cachexia and anorexia. AB - The aim is to review major clinical trials that have used megestrol acetate (MA) in the treatment of cachexia across several disease states. A review of general usage and potential side-effects are discussed. A theory that the newly approved nanocrystal formation of MA can better deliver this potent medication for treatment will also be reviewed. PMID- 17722276 TI - Optimizing efficacy of amphotericin B through nanomodification. AB - Fungal infections and leishmaniasis are an important cause of morbidity and mortality in immunocompromised patients. The macrolide polyene antibiotic amphotericin B (AmB) has long been recognized as a powerful fungicidal and leishmanicidal drug. A conventional intravenous dosage form of AmB, AmB- deoxycholate (Fungizone or D-AmB), is the most effective clinically available for treating fungal and parasitic (leishmaniasis) infections. However, the clinical efficacy of AmB is limited by its adverse effects mainly nephrotoxicity. Efforts to lower the toxicity are based on synthesis of AmB analogues such as AmB esters or preparation of AmB-lipid associations in the forms of liposomal AmB (L-AmB or AmBisome), AmB lipid complex (Abelcet or ABLC), AmB colloidal dispersion (Amphocil or ABCD), and intralipid AmB. These newer formulations are substantially more expensive, but allow patients to receive higher doses for longer periods of time with decreased renal toxicity than conventional AmB. Modifications of liposomal surface in order to avoid RES uptake, thus increased targetability has been attempted. Emulsomes and other nanoparticles are special carrier systems for intracellular localization in macrophage rich organs like liver and spleen. Injectable nano-carriers have important potential applications as in site-specific drug delivery. PMID- 17722277 TI - Potential diagnostic applications of biosensors: current and future directions. AB - This review describes recent advances in biosensors of potential clinical applications. Biosensors are becoming increasingly important and practical tools in pathogen detection, molecular diagnostics, environmental monitoring, food safety control as well as in homeland defense. Electrochemical biosensors are particularly promising toward these goals arising due to several combined advantages including low-cost, operation convenience, and miniaturized devices. We review the clinical applications of electrochemical biosensors based on a few selected examples, including enzyme-based biosensors, immunological biosensors and DNA biosensors. PMID- 17722278 TI - Nanocrystalline silver dressings in wound management: a review. AB - This paper describes the properties of nanocrystalline silver products (Acticoat) and their applications and examines available evidence supporting their use in wound management. Acticoat utilizes nanotechnology to release nanocrystalline silver crystals. Acticoat releases 30 times less silver cations than silversulfadiazine cream or 0.5% silver nitrate solution but more of the silver released (by Acticoat). Silver-impregnated slow-release dressings release minute concentrations of silver which are quickly bound up by the chloride in the wound exudate. While extrapolations from in vitro and animal studies are cautious, evidence from these studies suggests Acticoat is: effective against most common strains of wound pathogens; can be used as a protective covering over skin grafts; has a broader antibiotic spectrum activity; and is toxic to keratinocytes and fibroblasts. Animal studies suggest a role for nanocrystalline silver in altering wound inflammatory events and facilitation of the early phase of wound healing. Quality human clinical trials into nanocrystalline silver are few. However, evidence suggests using Acticoat in wound management is cost effective, reduces wound infection, decreases the frequency of dressing changes and pain levels, decreases matrix metalloproteinase activity, wound exudate and bioburden levels, and promotes wound healing in chronic wounds. Although there is no in vivo evidence to suggest nanocrystalline silver is toxic to human keratinocytes and fibroblasts, there is in vitro evidence to suggest so; thus these dressings should be used cautiously over epithelializing and proliferating wounds. Future clinical research, preferably randomized controlled trials into nanocrystalline silver technology, may provide clinicians a better understanding of its applications in wound management. PMID- 17722279 TI - Silicon nanoparticles: applications in cell biology and medicine. AB - In this review, we describe the synthesis, physical properties, surface functionalization, and biological applications of silicon nanoparticles (also known as quantum dots). We compare them against current technologies, such as fluorescent organic dyes and heavy metal chalcogenide-based quantum dots. In particular, we examine the many different methods that can be used to both create and modify these nanoparticles and the advantages they may have over current technologies that have stimulated research into designing silicon nanoparticles for in vitro and in vivo applications. PMID- 17722281 TI - Micro- and nanofabrication methods in nanotechnological medical and pharmaceutical devices. AB - Micro- and nanofabrication techniques have revolutionized the pharmaceutical and medical fields as they offer the possibility for highly reproducible mass fabrication of systems with complex geometries and functionalities, including novel drug delivery systems and bionsensors. The principal micro- and nanofabrication techniques are described, including photolithography, soft lithography, film deposition, etching, bonding, molecular self assembly, electrically induced nanopatterning, rapid prototyping, and electron, X-ray, colloidal monolayer, and focused ion beam lithography. Application of these techniques for the fabrication of drug delivery and biosensing systems including injectable, implantable, transdermal, and mucoadhesive devices is described. PMID- 17722280 TI - Molecular profiling of single cancer cells and clinical tissue specimens with semiconductor quantum dots. AB - Semiconductor quantum dots (QDs) are a new class of fluorescent labels with broad applications in biomedical imaging, disease diagnostics, and molecular and cell biology. In comparison with organic dyes and fluorescent proteins, quantum dots have unique optical and electronic properties such as size-tunable light emission, improved signal brightness, resistance against photobleaching, and simultaneous excitation of multiple fluorescence colors. Recent advances have led to multifunctional nanoparticle probes that are highly bright and stable under complex in vitro and in vivo conditions. New designs involve encapsulating luminescent QDs with amphiphilic block copolymers, and linking the polymer coating to tumor-targeting ligands and drug-delivery functionalities. These improved QDs have opened new possibilities for real-time imaging and tracking of molecular targets in living cells, for multiplexed analysis of biomolecular markers in clinical tissue specimens, and for ultrasensitive imaging of malignant tumors in living animal models. In this article, we briefly discuss recent developments in bioaffinity QD probes and their applications in molecular profiling of individual cancer cells and clinical tissue specimens. PMID- 17722282 TI - Influence of biologically inspired nanometer surface roughness on antigen antibody interactions for immunoassay-biosensor applications. AB - Current research efforts to improve immunoassay-biosensor functionality have centered on detection through the optimal design of microfluidic chambers, electrical circuitry, optical sensing elements, and so on. To date, little attention has been paid to the immunoassay-biosensor membrane surface on which interactions between antibodies and antigens must occur. For this reason, the objective of the present study was to manipulate the nanometer surface roughness of a model immunoassay-biosensor membrane to determine its role on sensitivity and specificity. It was hypothesized that surface roughness characteristics similar to those used by the body's own immune system with B-lymphocyte cell membranes would promote antigen-antibody interactions and minimize non-specific binding. To test this hypothesis, polystyrene 96-well plate surfaces were modified to possess similar topographies as those of B-lymphocyte cell membranes. This was accomplished by immobilizing Protein A conjugated gold particles and Protein A conjugated polystyrene particles ranging in sizes from 40 to 860 nm to the bottom of polystyrene wells. Atomic force microscopy results provided evidence of well-dispersed immunoassay-biosensor surfaces for all particles tested with high degrees of biologically inspired nanometer roughness. Testing the functionality of these immunosurfaces using antigenic fluorescent microspheres showed that specific antigen capture increased with greater nanometer surface roughness while nonspecific antigen capture did not correlate with surface roughness. In this manner, results from this study suggest that large degrees of biologically inspired nanometer surface roughness not only increases the amount of immobilized antibodies onto the immunosurface membrane, but it also enhances the functionality of those antibodies for optimal antigen capture, criteria critical for improving immunoassay-biosensor sensitivity and specificity. PMID- 17722283 TI - Propaedeutic study for the delivery of nucleic acid-based molecules from PLGA microparticles and stearic acid nanoparticles. AB - We studied the mechanism governing the delivery of nucleic acid-based drugs (NABD) from microparticles and nanoparticles in zero shear conditions, a situation occurring in applications such as in situ delivery to organ parenchyma. The delivery of a NABD molecule from poly(DL-lactide-co-glycolide) (PLGA) microparticles and stearic acid (SA) nanoparticles was studied using an experimental apparatus comprising a donor chamber separated from the receiver chamber by a synthetic membrane. A possible toxic effect on cell biology, as evaluated by studying cell proliferation, was also conducted forjust PLGA microparticles. A mathematical model based on the hypothesis that NABD release from particles is due to particle erosion was used to interpret experimental release data. Despite zero shear conditions imposed in the donor chamber, particle erosion was the leading mechanism for NABD release from both PLGA microparticles and SA nanoparticles. PLGA microparticle erosion speed is one order of magnitude higher than that of competing SA nanoparticles. Finally, no deleterious effects of PLGA microparticles on cell proliferation were detected. Thus, the data here reported can help optimize the delivery systems aimed at release of NABD from micro- and nanoparticles. PMID- 17722285 TI - Less harmful acidic degradation of poly(lacticco-glycolic acid) bone tissue engineering scaffolds through titania nanoparticle addition. AB - In the last 10 years, biodegradable aliphatic polyesters, such as poly(lactic-co glycolic acid) (PLGA), have attracted increasing attention for their use as scaffold materials in bone tissue engineering because their degradation products can be removed by natural metabolic pathways. However, one main concern with the use of these specific polymers is that their degradation products reduce local pH, which in turn induces an inflammatory reaction and damages bone cell health at the implant site. Thus, the objective of the present in vitro study was to investigate the degradation behavior of PLGA when added with dispersed titania nanoparticles. The results of this study provided the first evidence that the increased dispersion of nanophase titania in PLGA decreased the harmful change in pH normal for PLGA degradation. Moreover, previous studies have demonstrated that the increased dispersion of titania nanoparticles into PLGA significantly improved osteoblast (bone-forming cell) functions (such as adhesion, collagen synthesis, alkaline phosphatase activity, and calcium-containing minerals deposition). In this manner, nanophase titania-PLGA composites may be promising scaffold materials for more effective orthopedic tissue engineering applications. PMID- 17722286 TI - [Clinical assessment of modified segmental tuberculin test in infiltrative pulmonary tuberculosis and community-acquired pneumonia]. AB - The atypical course of pneumonias (without significant intoxication and bronchopulmonary syndromes) is now notified and the incidence of nonspecific changes in the lower lung has increased. The authors propose to use a modified segmental tuberculin test in the differential diagnosis of community-acquired pneumonia and pulmonary tuberculosis. This test has revealed that in community acquired pneumonia, the average sizes of papules do not differ in the bilateral suprascapular regions and they are significantly less than on the fore-arm when the Mantoux test with 2TE whereas in infiltrative pulmonary tuberculosis, the largest papules are recorded above a specific inflammatory focus and their size is larger than that on the intact side and forearm. PMID- 17722284 TI - Adriamycin release from poly(lactide-coglycolide)-polyethylene glycol nanoparticles: synthesis, and in vitro characterization. AB - The preparation, properties, and application in adriamycin delivery ofbiocompatible and biodegradable poly(lactide-co-glycolide)-polyethylene glycol (PLGA-PEG) nanoparticles are discussed. PLGA-PEG copolymers were synthesized by ring opening polymerization of the dl-lactide and glycolide in the presence of PEG1000. 1H-NMR and FT-IR spectrum were consistent with the structure of PLGA-PEG copolymers. The adriamycin-loaded nanoparticles could be prepared using a precipitation-solvent evaporation technique. The nanoparticles have been produced by a precipitation-solvent evaporation technique. The physical characteristics and drug loading efficiency of the PLGA-PEG nanoparticles were influenced by the composition of the PLGA-PEG copolymers used to prepare the nanoparticles. Particle sizes were between 65 and 100 nm for different compositions of PLGA-PEG copolymers. PLGA-PEG nanoparticles prepared from copolymers having relatively high PLGA/PEG ratios were smaller. Entrapment efficiency was 25%-33%. Adriamycin release from the nanoparticles at pH 7.4 showed an initial burst release and then sustained release phase. These results showed that PLGA-PEG nanoparticles could be an effective carrier for cancer therapy. PMID- 17722287 TI - [Extrapulmonary tuberculosis in HIV-infected patients]. AB - The authors analyze 143 cases of extrapulmonary and generalized tuberculosis in HIV-infected patients. There is a steady increase in the number of patients with multiple organ tuberculosis that frequently acquires the pattern of an acute generalized septic process. Generalized tuberculosis predominantly develops in HIV-infected patients with a considerable reduction in immunological parameters and it is, in these cases, of primary generalized nature. The efficiency of treatment is very low in patients with multiple organ tuberculosis. Despite therapy, the progression of the disease results in early death. However, the prospects for further inclusion of highly active antiretroviral therapy in multimodality treatment for comorbidity give hope for the solution of this problem. PMID- 17722288 TI - [Study of the polymorphic markers--the PARK2 and PACRG genes due to the incidence of pulmonary tuberculosis in two districts of the Republic of Tyva]. AB - Polymerase chain reaction-RFLP was used to distribute two polymorphic markers (SNP) PARK2-e01 (-697) and rs1333955 located at the common promoter site of the PARK2 and PACRG genes in order to reveal assumed associations with the incidence of pulmonary tuberculosis in the Barum-Khemchiksky and Ovyursky Districts of the Republic of Tyva. No significant differences were found in the frequencies of these two polymorphic markers between the groups of patients with tuberculosis and healthy individuals, residing in the above districts, and between the total control samples from both districts. The total group of patients with tuberculosis from the two districts from the Republic of Tyva showed a significant surplus of heterozygotes in both study markers, as compared with the group of healthy individuals, which was also observed for the marker rs1333955 in the Barum-Khemchksky District alone. The observed features of genotypic distribution by the two study markers point to the influence of the considered markers on the incidence of tuberculosis. PMID- 17722291 TI - [Use of a mini-sequencing test, followed by the MALDI-TOF mass-spectrometric analysis to evaluate rifampicin and izoniazid resistance in Mycobacterium tuberculosis circulating in the Russian Federation]. PMID- 17722290 TI - [Statistically mapping modeling of the spread of rifampicin-resistant M. tuberculosis strains in different regions of the Kyrghyz Republic]. AB - Mapping modeling of the distribution of rifampicin-resistant tuberculosis was made in different regions of the Kyrghyz Republic. The results of determination of rifampicin resistance in Mycobacterium tuberculosis (MBT) by the biochip test were used to examine 904 MBT DNA samples taken when examining the patients living in different regions of the Kyrghyz Republic: Bishkek (n = 323), the Chui (n = 185), Issyk-Kul (n = 68), Naryn (n = 75), Talas (n = 47), Osh (n = 65), Dzhalal Abad (n = 90), and Batken (n = 51) Regions. Comparison of the distribution of drug-resistant forms of tuberculosis by different regions revealed that rifampicin-resistant MBT strains were more frequently encountered in the densely populated regions of the republic - Bishkek and the Chui Region. Rifampicin resistance in MBT was caused by mutations in codons 531, 526, 522, 516, 511, 513, 512, and 513 of the rpoB gene. At the same time, there was a predominant selection of MBT with mutations in codons 531, 526, 516, and 511 in the republic. The spectrum of mutant MBT strains occurring in some regions varied. The broadest spectrum of genetic variability was observed in Bishkek and the Chui Region. Thus, Bishkek and the Chui Region are the hot points of concentration of mutant rifampicin-resistant MBT strains. PMID- 17722292 TI - [To the classification of tuberculosis of organs of vision]. PMID- 17722289 TI - [Monitoring of drug resistance in Mycobacterium tuberculosis in the Republic of Sakha (Yakutia)]. AB - The paper analyzes the detection rate of drug-resistant (DR) Mycobacterium tuberculosis (MBT) in Yakutia. The proportion of DR MBT strains taken from bacterial isolating patients with pulmonary tuberculosis was found to be 70% and to have no tendency for decrease. The structure of DR MBT deteriorated due to the increase in multidrug-resistance (MDR). MDR in MBT was recorded in 45-50% of cases. Examination of lung resection specimens from patients with abacillary tuberculosis identified a population of typical MBT. The authors regarded this phenomenon as latent MBT carriage. The specific feature of this population is that it preserves a high metabolic activity in latency; DR was established in 76.3% of patients. Its most malignant form - MDR was established in a third (31.6%) of the patients. Under certain conditions, this mycobacterial infection may be of epidemic value in the spread of MBT in general and MDR strains in particular. Solution of the problems associated with the surgical treatment of patients with MDR tuberculosis may be beneficial in diminishing the most dangerous reservoir of tuberculous infection. Surgical intervention in MDR tuberculosis is one of the basic treatments. PMID- 17722293 TI - [On the seeming and real atherogenicity of LDLP-IgG immune complexes in blood plasma and the arterial wall]. AB - LDLP-antibody immune complexes and free LDLP were isolated from the serum and aortal wall of people who had died of myocardial infarction; their atherogenicity was compared on the basis of their capture by mouse peritoneal macrophages. The experiment showed that the capture of serum and aortal autoimmune LDPT-antibody complexes was approximately 2.5 times higher than that of free serum lipoproteins (mostly native ones). However, the capture of free (mostly modified) aortal LDLP was approximately 3.6 times higher than that of aortal immune complexes. According to the data received, the comparative atherogenicity of immune complexes and free lipoproteins can be ranked in the following order: modified LDLP --> modified LDLP-IgG complex --> native LDLP. The study shows that LDLP antibody immune complexes formed in a rabbit's organism get extremely quickly eliminated from bloodstream, probably due to their active capture by reticuloendothelial system cells. The authors suggest that the formation of antilipoprotein autoantibodies and lipoprotein-antibody complexes is a protective response of the organism to appearance of highly atherogenic modified lipoproteins directed towards the weakening of the atherogenicity of such lipoproteins and the intensification of their elimination from bloodstream. PMID- 17722294 TI - [The evolution of antihypertensive pharmacotherapy in Great Patriotic War veterans]. AB - The subjects of the study were 1500 Great Patriotic War veterans, examined in 2000, and 1545 ones, examined in 2005. In each of these groups, 856 (79.3% and 77.8%, respectively) subjects had arterial hypertension. The authors analyze substantial modifications in out-patient antihypertensive therapy of this category of patients which have taken place in the last five years. PMID- 17722295 TI - [Antibody-mediated proteolysis of myelin-associated proteins as a new mechanism of control over demyelinization processes in multiple sclerosis]. AB - Natural antibodies possessing catalytic activity present a new group of biologically active substances that are found in various autoimmune diseases such as autoimmune thyroiditis, myocarditis, multiple sclerosis, and system lupus erythematosus. Presently, an interconnection between the activity of these antibodies and the extent of organic and tissue lesion in autoaggression have been revealed. Clinical use of catalytic antibodies as a diagnostic criterion to evaluate the severity of disease, a prognostic criterion of the risk of invalidization, and as a pathogenetic basis for medicamentous treatment of autoimmune process is a promising directions of study of the role of catalytic antibodies. PMID- 17722296 TI - The association of apolipoprotein B and low density lipoprotein with cardiovascular risk factors in the Thai population. AB - BACKGROUND: Although direct and calculated low density lipoprotein cholesterol (LDL-cholesterol) has been widely used as an important predictor for cardiovascular risk, many studies have shown that apolipoprotein B (apo B) may be a more important lipoprotein marker. MATERIAL AND METHOD: We performed a cross sectional study on 191 volunteers who were Shinawatra employees during their annual physical check up. The following cardiovascular risk factors were recorded or measured: direct and calculated LDL, apo B, gender age, total cholesterol, triglyceride, HDL-cholesterol (HDL), calculated LDL, fasting plasma glucose (FPG), systolic and diastolic blood pressure, smoking status, body mass index (BMI), waist circumference, and waist-hip ratio (WHR). Apo B, direct LDL and calculated LDL levels were tested for their associations with other potential cardiovascular risk factors. RESULTS: There were a total of 76 men and 115 women with an average age of 28.8 +/- 5.4 years. Male gender, cigarette smoking, high cholesterol, high triglyceride, high fasting plasma glucose, hypertension, high WHR and high BMI were associated with increased apo B level. Only male gender and high cholesterol were associated with increased calculated and direct LDL level. The association of direct and calculated LDL-cholesterol level with cardiovascular risk factors appears to be similar. CONCLUSION: We demonstrated that apo B level correlates more with other cardiovascular risk factors compared to direct and calculated LDL-cholesterol. The clinical relevance of this finding needs to be explored in large-scale studies. PMID- 17722297 TI - Prevalence of erectile dysfunction among treated hypertensive males. AB - OBJECTIVE: Study the prevalence rate of erectile dysfunction (ED) in treated hypertensive males. MATERIAL AND METHOD: Four hundred and twenty nine patients attending the outpatient clinic at Siriraj Hospital between April 2001 and October 2002 were interviewed. The International Index of Erectile Function, a 5 item version (IIEF-5) questionnaire was used. All questions were carried out by a well-trained interviewer. RESULT: Of the 429 patients (mean age of 57.5 +/- 12.0 years) interviewed, 241 cases (56.2%) reported ED. The prevalence was found to increase with age: from 0% in men aged < 40 years, 47.4% in men aged 40-59 years, and 75.3% in men aged > 60 years. Risk of ED was significantly (p < 0. 01) associated with the elderly (OR = 4.7, 95%CI= 3.1-7.1), patients who suffered from hypertension longer than 5 years (OR = 4.0, 95%CI = 2.6-6.1), those with a history of back/pelvic surgery (OR = 2.8, 95%CI = 1.4-4.8), smoking (OR = 1.5, 95%CI = 1.0-2.2), alcohol ingestion (OR = 2.0, 95%CI = 1.3-3.0), diabetes mellitus (OR = 6.3, 95%CI = 3.5-11.2), diuretics (OR = 1.9, 95%CI = 1.3-2.8), and alpha-2 agonist (OR = 7.9, 95%CI = 2.3-26.1) usage. On multivariate regression analyses, the elderly (OR = 4.0, 95%CI = 2.5-6.4), diabetes mellitus (OR = 6.4, 95%CI = 3.5-11.8), the usage of diuretic (OR = 2.1, 95%CI = 1.3-3.4), and alpha-2 agonist (OR = 6.0, 95%CI = 1.7-21.3) predicted ED (p < 0.005 in all categories). Neither history of back/pelvic operation, smoking, alcohol ingestion, overweight (BMI > or = 30 kg/m2), or any other antihypertensive medications independently predicted ED. CONCLUSION: Our results indicated that ED in male hypertensive patients is common and the cause should be sought and avoided. Diabetic patients or those who have been using diuretic or alpha-2 agonists should receive much attention and be routinely evaluated for ED. PMID- 17722298 TI - Difference in the yields of bronchial washing cytology before and after forceps biopsy for lung cancer diagnosis. AB - OBJECTIVES: Fiberoptic bronchoscopy (FOB) has been one of the essential procedures used in the diagnosis of lung cancer Diagnostic yields of FOB related procedures such as bronchial washing (BW), bronchial brushing (BB), bronchial biopsy (BBx), and transbronchial biopsy (TBBx) depend on the location and extent of the tumors. The yields of BW vary among different studies (39-79%). Some reported that the yield might increase in post-bronchoscopic sputum. Since samples from BW are obtained directly from the respiratory tract, we hypothesized that post bronchoscopic forceps biopsy BW might further increase the yield as well. The objective of this study was to compare the diagnostic yields of bronchial washing before and after forceps biopsy for lung cancer. MATERIAL AND METHOD: 114 patients, 70 with endobronchial lesions (42 exophytic lesions, 28 submucosal lesions) and 44 with non-endobronchial lesions, suspected to have lung cancers were evaluated at Siriraj Hospital between March and October 2000. All the patients underwent FOB with initial BW then forceps biopsy (BBx or TBBx) of the lesions followed by re-BW. The cytological specimens were blinded to the cytopathologists. Positive cytologic results of each procedural specimen were compared to final malignancy diagnosis (by positive specimens from FOB, transthoracic needle aspiration, surgery, clinical and radiological follow-up) to determine the sensitivity of each test. STATISTICAL ANALYSIS: Chi-square test comparing sensitivity of each test. RESULTS: 82/114 patients (39 patients had exophytic lesions, 24 patients had submucosal lesions, and 19 patients had peripheral lung lesions) had a final diagnosis of malignancy. The sensitivity of initial BW before forceps biopsy was 37.8% (31/82), re-BW after forceps biopsy was 37.8% (31/82), both initial BW and re-BW was 46.3% (38/82), and forceps biopsy alone was 79.3% (65/82). There was no statistically significant difference (p > O.05) in the sensitivity of initial BW re-BW and combined initial BW and re BW. No major complications such as massive hemorrhage, respiratory failure, or death occurred. CONCLUSION: The diagnostic yields of BW before and after forceps biopsy for malignancy were not different in our study. However, the yield seemed to be higher when combined pre and post-forceps biopsy BW was used. PMID- 17722299 TI - Association between HLA class II alleles and autoimmune hepatitis type 1 in Thai patients. AB - OBJECTIVE: To investigate the association between HLA class II alleles and autoimmune hepatitis (AIH) type I in Thai patients. MATERIAL AND METHOD: The clinical data of 50 autoimmune hepatitis patients type I (AIH) at Siriraj hepatitis clinic were analysed, 37 of whom were tested for HLA class II genotyping using polymerase chain reaction and sequence-specific oligonucleotide technique (PCR-SSO). RESULTS: AIH is an uncommon chronic hepatitis in Thailand with females predominant. The HLA DRB1*0301, and DQA1*0101 were significantly associated with AIH patients when compared to controls; (OR = 3.92 [1.18-13.30], p 0.021, OR = 2.31 [1.13-4.73], p 0.019, respectively). When 18 patients with "definite" AIH were analysed, only HLA DRB1*0301 was still significantly associated with AIH (OR = 5.22, 95%CI = 1.28-20.92, p 0.015). CONCLUSION: HLA genotyping has shown that HLA DRB1*0301 and HLA DQA1*0101 were significantly associated with AIH. PMID- 17722301 TI - Epidemiology of Staphylococcus aureus infections and the prevalence of infection caused by community-acquired methicillin-resistant Staphylococcus aureus in hospitalized patients at Siriraj Hospital. AB - BACKGROUND: The CA-MRSA infections have emerged in many parts of the world over the past decade. To our knowledge, the prevalence of CA-MRSA infections in Thai patients is unknown. OBJECTIVE: To determine an epidemiology of Staphylococcus aureus (S. aureus) infections in hospitalized patients in Siriraj Hospital and the prevalence of infections caused by community-acquired methicillin-resistant S. aureus (CA-MRSA). MATERIAL AND METHOD: The study was carried out at Siriraj Hospital from January to May 2005. The eligible patients were hospitalized patients whom S. aureus were isolated from their clinical specimens submitted to Department of Microbiology. S. aureus isolate was classified into infection or colonization. S. aureus infections were further classified into methicillin resistant S. aureus (MRSA) or methicillin-sensitive S. aureus (MSSA) infections, and hospital-acquired (HA) or community-acquired (CA) infections. CA-MRSA infection is defined as infection caused by MRSA isolated from the patient within 72-hour of hospitalization and has no features of HA MRSA infections. RESULTS: There were 669 S. aureus isolates from 448 patients. Two hundred and sixty two patients (58.5%) were MSSA whereas 186 (41.5%) were MRSA infections. CA-MRSA was found in three isolates (0.9% of total MRSA) from two patients. CONCLUSION: The prevalence of CA-MRSA infections in hospitalized patients in Siriraj Hospital was uncommon and these patients could probably be HA MRSA infections. PMID- 17722300 TI - Risk factors of hepatitis C virus infection in blood donors in Thailand: a multicenter case-control study. AB - OBJECTIVE: To investigate the risk of hepatitis C virus (HCV) infection in healthy blood donors in Thailand MATERIAL AND METHOD: We performed a case-control study of 435 HCV-seropositive blood donors and 894 HCV-seronegative blood donors as controls. The study was done with direct interview regarding demographic characteristics and risk factors. Odds ratios (OR) with 95% confidence intervals (CIs) were calculated by using conditional logistic regression. RESULTS: The final multivariable model included only the following independent HCVrisk factors: intravenous drug user (IDU) (OR = 61.5; 95%CI, 26.6-142.5), previous blood or blood products transfusion (OR = 12.3; 95%CI, 7.6 -19.9), sharing of razors (OR = 2.3, 95%CI, 1.6-3.2),unsafe injection (OR = 3.3, 95%CI, 1.8-5.9), unused condom (OR = 1.6; 95%CI, 1.1, 2.4). No risk was shown for a history of tattoo, ear piercing, or acupuncture and multiple sexual partners. CONCLUSION: The risk factors for HCV infection in healthy blood donors in Thailand are IDU, past history of blood transfusion and unsafe injection. PMID- 17722302 TI - Correlation between volumes and circumferences of residual limb in below knee amputees. AB - OBJECTIVE: To determine the correlation between the stump circumference at different levels (at tibial tubercle, 4-cm, 8-cm and the distal end) with the stump volumes in below knee amputees. DESIGN: Cross sectional descriptive design. SETTING: King Chulalongkorn Memorial Hospital and Sirindhorn National Medical Rehabilitation Center PARTICIPANTS: Fifty five unilateral below knee amputees were recruited from the outpatient rehabilitation department. MEASUREMENT: Residual limb volumes of each subject were measured by water displacement method with volumeter and measured different circumferences level with a tape twice for each method. RESULTS: The Pearson correlation coefficients of residual limb volume and circumference at tibial tubercle level, 4- and 8- cm from the tubercle, and distal end level were 0.814, 0.892, 0.878, and 0. 715, respectively. CONCLUSION: The results revealed significant correlation in all levels studied. Maximum correlation coefficient was observed at 4 centimeters below tibial tubercle. PMID- 17722303 TI - IQOL: translation & reliability for use with urinary incontinence patients in Thailand. AB - BACKGROUND AND OBJECTIVE: Urinary incontinence is consistently associated with an adverse effect on the quality of life (QoL) for patients. The I-QOL is a self report quality-of-life measure specific to urinary problems that can be used to assess the impact of urinary incontinence and urinary problems (such as overactive bladder without incontinence) and their treatment. The objectives of the present study were to develop and test the reliability of a Thai version of the Incontinence Quality of Life Questionnaires (IQOL). MATERIAL AND METHOD: The I-QOL was formally translated from the original version to the Thai language with Permission. The translation process included forward translation by 2 translators. Cultural and linguistic modifications ofbothforward versions were done by a group of urologists who had extensive experience in the management of urinary incontinence. Another two Thai-English translators performed the back translation into English. Enrolled subjects included urinary incontinence patient and normal subjects were asked to complete the translated versions of I-QOL and repeated the same two weeks apart for test-retest analysis. Reliability was determined from Cronbach's alpha (reliability coefficient). Pearson's correlation was used to assess test-retest reliability. RESULTS: A 22 items questionnaire was developed. Sixty patients with urinary incontinence and fifty normal subjects were enrolled into the present study. Mean ages (SD) of patients with incontinence and controlled groups were 52.42(13.54) and 48.22(10.27) years. Of the 60 patients with urinary problems, 15(13.6%) had stress urinary incontinence (SUI), 17(15.5%) had overactive bladder (OAB), 13(11.8%) had mixed urinary incontinence, 15(13.6%) had urge urinary incontinence from BPH. The mean scores(SD) of I-QOL in the normal group was 89.63(12.64) and 57.65(20.04) in the urinary incontinence group. Cronbach's alpha of the overall IQOL scores was 0.96. Test-retest reliability done at 2 weeks apart was 0.905. CONCLUSION: The translated I-QOL is valid and applicable in Thais with urinary incontinence problems. I-QOL score reveals that QOL in these patients is lower than that in the normal population. PMID- 17722304 TI - Efficacy of topical vitamin C derivative (VC-PMG) and topical vitamin E in prevention and treatment of UVA suntan skin. AB - Exposure to ultraviolet radiation is known to cause many adverse side effects by inducing the tissue to produce reactive oxygen species. By inhibiting these mediators, administration ofantioxidants might be the strategy to reduce UVA induced skin reaction such as tissue damage and inflammation. However the present study showed that administration of topical 10% vitamin C derivative (VC-PMG) and topical 5% vitamin E has no effect in terms ofprevention or treatment of UVA suntan skin in 20 volunteers. Prior to 30 Joules UVA exposures, they were asked to apply both agents twice daily for 3 days. Then, the melanin index was measured immediately after irradiation by using the Maxemeter which was insignificant at the 95% level of confidence compared with the placebo. After continuing the cream application for 12 weeks, there were also no bleaching effects observed after 2, 4, 6, 8, 10 and 12 weeks compared to the placebo. PMID- 17722305 TI - Evaluation of the bioequivalence of zidovudine 100 mg capsules in healthy Thai male volunteers. AB - OBJECTIVE: The bioequivalence study of two oral formulations of zidovudine were evaluated; Antivir (Government Pharmaceutical Organization (GPO), Thailand) as the test formulation and Retrovir (Glaxo-SmithKline, USA), as the reference formulation. MATERIAL AND METHOD: The two products were orally administered as a single dose of 100 mg zidovudine three capsules according to a randomized two-way crossover design to 28 healthy fasted Thai male volunteers. The washout period between treatments was 1 week. After drug administration, serial blood samples were collected at a specific time interval from 0-10 hours. The plasma zidovudine concentrations were determined via HPLC technique. Individual plasma zidovudine concentration-time profile was analyzed for relevant pharmacokinetic parameters; the comparative bioavailability of the two products was determined by the analysis of variance (ANOVA) for two way crossover design, using logarithmic transformed data. RESULTS: The results found that the mean peak (X+/- SD) plasma concentration (Cmax) of Antivir was 3.34 +/- 0.15 ng/mL and of Retrovir was 3.32 +/- 0.21 ng/mL. The 90% confidence interval (CI) for the difference of mean Cmax was 90.76-120.81%. The time to peak plasma concentration (Tmax) of Antivir was 0.49 +/- 0.16 hours and for Retrovir was 0.62 +/- 0.35 hours with a difference time to peak of 20.96%. The half life (t1/2) of Antivir was 1.16 +/- 0.28 hours and t1/2 of Retrovir was 1.05 +/- 0.25 hours. The mean area under the curve (AUC0 ->t) of Antivir was 3.34 +/- 0.12 ng.hr/mL and of Retrovir was 3.35 +/- 0.15 ng.hr/mL. The 90%CI for the difference ofmean AUC0-->t was 91.83-103.99%. The mean AUC0-->infinity of Antivir was 3.37 +/- 0.12 nghr/mL and for and Retrovir was 3.38 +/- 0.14 ng.hr/mL. The 90%CI for the difference of mean AUC0-->infinity was 91.22-104.69%. CONCLUSION: The present study revealed that the 90%CI for the difference of Cmax AUC0-->t and AUC0-->infinity means were in the criteria ofacceptance, which should be within 80-125%. Thus, the present study demonstrated the bioequivalence of the test drug (Antivir) and the reference drug (Retrovir). PMID- 17722308 TI - Keratometry in Thai children from newborn to the age of ten: a retrospective study. AB - OBJECTIVE: To study the corneal curvature in Thai children, from newborn to ten years. MATERIAL AND METHOD: The authors reviewed keratometric reading of Thai children obtained from January 1st, 2003 to December 31st, 2005. Data was analyzed in stratified pattern based on their age groups. RESULTS: 360 eyes from 183 patients were enrolled. The keratometric reading (K) was ranged between 43-44 diopters, there was no statistically significant difference among mean K in all age groups (ANOVA, RE p = 0.612, LE p = 0.608). There was no correlation between absolute corneal astigmatism of each age group and age (Pearson correlation, RE r = -0.20, p = 0.006, LE r = -0.11, p = 0.11). The most common corneal astigmatism was with the rule type in all age groups. CONCLUSION: The keratometric reading was consistent in all age groups in the range between 43-44 diopters. There was no correlation of absolute corneal astigmatism and increasing age. With the rule astigmatism was the most common corneal astigmatism. PMID- 17722306 TI - Pain on injection of propofol: propofol LCT vs propofol MCT/LCT with or without lidocaine pretreatment. AB - BACKGROUND: Pain on injection was a disadvantage of propofol long-chain triglyceride (LCT) and reduces patient satisfaction. Based on a systematic review, the recommended method to attenuate this pain was a previous administration of lidocaine under tourniquet for 30-120 seconds before injection of propofol (pretreatment of lidocaine). Recently, propofol medium-chain triglyceride/long-chain triglyceride (MCT/LCT) emulsion was proposed for its ability to decrease pain on injection. The authors conducted a double-blind randomized controlled trial to compare the incidence and severity of pain on injection between the new propofol MCT/LCT and the propofol LCT with and without lidocaine pretreatment. MATERIAL AND METHOD: 360 adult patients with ASA physical status I-III who underwent general anesthesia were assigned into 4 groups by computer-generated randomization; Group I - pretreatment of lidocaine 1% and propofol LCT Group I - pretreatment oflidocaine 1% and propofol MCT/LCT Group III - pretreatment of saline and propofol MCT/LCT and Group IV- pretreatment of saline and propofol LCT mixed with lidocaine 1%. All groups received pretreatment under tourniquet for 60 seconds. Evaluators who were blinded to the injected drugs recorded pain intensity (none, mild, moderate and severe) after the first 30% of total induction dose ofpropofol was injected at a rate of 1 ml/s by questioning patients. Data was analyzed by using Kruskal-Wallis testfor ordinal data. Post hoc analysis was performed by using the Mann-Whitney U-test with Bonferroni's correction on pairwise comparisons and was considered significant with p value of less than 0.05. RESULTS: Patients in an individual group had insignificant differences in their demographic data. The incidences of pain in Group I, II, III and IV were 61.1%, 46.7%, 62.2% and 55.6% respectively with an average incidence of 56% (p = 0.006). There were 15.6%, 5.6%, 23.3% and 24.4% of patients in Group I, II, III and IV who rated pain intensity as severe. Pain on injection of propofol MCT/LCT with lidocaine pretreatment was less than propofol MCT/LCT alone (p = 0.001). CONCLUSION: The incidence of pain on injection of propofol MCT/LCT was not different from that caused by propofol LCT with pretreatment of lidocaine and the intensity of pain on propofol MCT/LCT injection decreased significantly when using lidocaine pretreatment. Therefore, the authors could conclude that an injection of new propofol MCT/LCT solution was an alternative in reducing pain sensation to propofol LCT with pretreatment of lidocaine. Additionally, pain of propofol MCT/LCT injection could be alleviated by pretreatment of lidocaine with a 60 seconds tourniquet time before the injection ofpropofol. PMID- 17722307 TI - Evaluation of Helicobacter pylori stool antigen test in Thai patients with upper gastrointestinal bleeding. AB - OBJECTIVE: Stool antigen test was evaluated in comparison with other diagnostic tests for the diagnosis of H. pylori infection in Thai patients presented with upper gastrointestinal bleeding. MATERIAL AND METHOD: Fifty-six patients were enrolled and fecal specimen was obtained from 34 patients. The presence of H. pylori was considered if the culture was positive or at lease two of the other diagnostic tests (urea breath test, serology, rapid urease test or histology) were positive. Stool antigen test was performed by using commercially available monoclonal enzyme immunoassay (Amplified IDEIA HpStAR, Dako, Denmark). RESULTS: Of the 56patients, 35 (62.5%0) were considered H. pylori infected, while in 34patients tested by stool antigen test, 22 (64.71%) were infected. The prevalence of H. pylori infection as determined by each test is considered low (47.06% from stool antigen test; 42.50%from UBT, 65.85%from serology; 51.78%0from RUT- and 46.34% from histology). The sensitivity/specificity/accuracy (%) of stool antigen test was 69.56/100/ 79.41 compared to 73.91/100/85 of UBT 79.17/52.94/68.29 of serology, 80/95.23/85.71 of RUT and 82.61/ 100/90.24 of histology, respectively. CONCLUSION: In summary, the results of this study reveal that the prevalence of H. pylori was relatively low in upper gastrointestinal bleeding patients. Yielding a low sensitivity and accuracy, the stool antigen test is therefore not reliable for the diagnosis of H. pylori infection in patients with upper gastrointestinal bleeding. PMID- 17722309 TI - The spread of avian influenza H5N1 virus; a pandemic threat to mankind. AB - Influenza A H5N1 virus infection presents a major public health problem in Asian and Eurasian countries. The World Health organization has voiced their concerns about a potential pandemic with the imminent threat to humankind. In 1997, an outbreak of highly pathogenic H5N1 virus emerged and caused severe systemic disease among poultry and humans in Hong Kong. This article reviews the magnitude of the 2004-2006 outbreaks in various countries and highlights the highly pathogenic avian influenza (HPAI) subtype H5N1 virus as the cause of a major epidemic with potentially vast repercussions on economics, public health and society at large. Not only has this avian influenza (AI) virus infected poultry but has also proven highly pathogenic and fatal to mammalian species including humans and felines. The present review draws a comprehensive picture encompassing epidemiology, inter-species transmission and genetic characterization of this highly virulent virus. Moreover, laboratory diagnostic techniques, vaccination strategies and antiviral therapies aimed at outbreak control and management are also discussed. PMID- 17722311 TI - The effects of implanon in the symptomatic treatment of endometriosis. AB - OBJECTIVE: To evaluate the efficacy of Implanon on treatment of symptomatic endometriosis DESIGN: An open clinical study without control group SETTING: Family Planning Clinic and out patient department, King Chulalongkorn Memorial Hospital, Bangkok, Thailand. MATERIAL AND METHOD: A total number of 50 women with symptomatic endometriosis who were diagnosed and confirmed by laparoscopy or whose symptoms recurred after surgical treatment were recruited in the study. These subjects were implanted Implanon subcutaneously at medial aspect of non dominant forearm. The intensity of pain was assessed with Visual Analog Scale (VAS) before insertion and at 4th and 12th weeks after the insertion. The adverse effects were recorded by the patients in 4th and 12th weeks of treatment. The women evaluated their satisfaction on treatment at the end of study. RESULTS: 50 women recruited in the study and all completed follow-up. Improvements of pain severity and menstrual symptoms were observed. The mean + SD Visual Analog Scale score of dysmenorrheal were 7.08 +/- 2.09 at baseline, 3.72 +/- 2.04 at 4th week, and 0.84 +/- 1.67 at 12th week of treatment. During the study period. regular menstruation, amenorrhea, spotting, and breakthrough bleeding were reported by 21 (42%). 14(28%), 13(26%), and 2(4%). At final satisfaction evaluation, 6(12%) women were very satisfied, 34 (68%) were satisfied, and 10(20%) were uncertain. All of acceptors continued to retaining the implant after study. CONCLUSION: Implanon, a sub-dermalprogestin implant is an effective hormonal alternative for treatment of symptomatic endometriosis. However women should be carefully counseled regarding menstrual changes. has the potential for providing long-term treatment of endometriosis. Nevertheless, the further study should be conducted to compare with other of modality of treatment. PMID- 17722310 TI - Treatment of idiopathic menorrhagia with tranexamic acid. AB - OBJECTIVE: To determine the efficacy of tranexamic acid in the treatment of idiopathic menorrhgia and to investigate the effect of medical treatment with tranexamic acid on the quality of life of the women with idiopathic menorrhagia. DESIGN: Open, non-comparative study. SETTING: Department of Obstetrics and Gynecology King Chulalongkorn Memorial Hospital. SUBJECTS: 40 women with idiopathic menorrhagia was confirmed by menstrual blood loss greater than 80 ml/ cycle (PBAC score > 100) and mid-luteal serum progesterone concentration greater than 5 pg/ml. INTERVENTION: Treatment with tranexamic acid 1 g orally, three times daily, for five days from day 1 of the menstruation for two consecutive menstrual periods. MAIN OUTCOME MEASURES: Menstrual blood loss was measured using the pictorial blood loss assessment chart (PBAC). Hematological assessments were made at the beginning, after the first treatment cycle and at the end of the study. Questionnaires were given to assess subjective endpoint, quality of life. Patients were asked to report any adverse event during the study period. RESULTS: Tranexamic acid reduces the mean PBAC score by 49%, from 350.5 to 178.6. Regarding the change in the quality of life measures, the proportion of women who felt a considerable degree of impairment during the menstruation was reduced from nearly 60% to less than 5% during their third menstruation. No serious adverse events were reported. CONCLUSION: Tranexamic acid is a safe and effective form of medical therapy in women with menorrhagia; also increases quality of life in these women. PMID- 17722312 TI - Effects of radiotherapy on sexual activity in women with cervical cancer. AB - OBJECTIVE: To assess changes in sexual activity in women treated for cervical cancer by radiotherapy over a period of 3 to 12 months. MATERIAL AND METHOD: Women treated for cervical cancer were selected at 3 to 12 months post-treatment. Main outcome measured were changes of sexual activity in sexual desire, arousal, orgasm, dyspareunia, frequency and satisfaction. Comparisons were made between after radiation and before radiation. RESULTS: The prevalence of sexual dysfunction increased in most patients treated with pelvic radiotherapy. There were significant reduction in sexual desire, arousal, orgasm, frequency of intercourse, and satisfaction after radiation. Increase in sexual pain was common after treatment, but was not significant in deep dyspareunia. Sexual frequency was significantly correlated with FIGO staging. CONCLUSION: Sexual activities were significantly reduced following radiotherapy. Educational and counseling programs on sexual activity after treatment should be provided to the patients. PMID- 17722314 TI - Extent of lymphovascular space invasion and risk of pelvic lymph node metastases in stage IB1 cervical cancer. AB - OBJECTIVE: To evaluate whether the extent of lymphovascular space invasion (LVSI) is a risk factor for pelvic lymph node metastases in stage IBI cervical cancer. MATERIAL AND METHOD: The clinicopathological data of 397 patients with stage IB1 cervical cancer undergoing radical hysterectomy and pelvic lymphadenectomy (RHPL) at Chiang Mai University Hospital between January 1998 and December 2002 were analyzed. The histology, tumor grade, depth of stromal invasion, uterine corpus involvement, parametrial invasion and LVSI were analyzed for their association with pelvic node metastases. The extent of LVSI was classified as negative, minimal (< 10 LVSI/cervical specimen), and extensive (> or = 10 LVSI/cervical specimen). RESULTS: Of the 397 patients, 146 (36.8%) had tumors containing LVSI, 82 (20.7%) and 64 (16.1%) had minimal and extensive LVSI, respectively. Fifty nine (14.9%) patients had pelvic node metastases. Using multivariable analysis, LVSI (p < 0.001), depth of stromal invasion (p < 0.001), tumor grade (p < 0.001), and parametrial invasion (p < 0.001) were significant predictors of pelvic node metastases. The extent of LVSI either minimal or extensive degree significantly influenced pelvic node metastases. CONCLUSION: The presence of LVSI especially extensive involvement was significantly associated with the risk of pelvic node metastases in stage IB1 cervical cancer. PMID- 17722313 TI - Histopathologic consistency between endometrial hyperplasia diagnosis from endometrial curettage and pathologic diagnoses from hysterectomy specimens. AB - OBJECTIVES: To evaluate the consistency between histopathology of endometrial hyperplasia (EMH) from endometrial curettage and those from the subsequent hysterectomy specimen. The co-incidental finding of endometrial carcinoma in patients with EMH was also studied. MATERIAL AND METHOD: All patients who had a diagnosis of EMH from the curettage procedure and underwent hysterectomy, between January 1995 and December 2004, were identified. The histopathology of the curettage specimens were compared to those of the hysterectomy specimens. RESULTS: The histopathologic subtypes of EMH from the curettage specimens of 46 patients included in the study were: simple or complex hyperplasia in 30 cases and atypical simple or complex hyperplasia in 16 cases. The consistency rate of endometrial tissue from curettage and hysterectomy specimens was 41.3%. The consistency rates were 62.5% and 30.0% in patients with atypical EMH and EMH without atypia respectively. Eight cases (17.4%) of EMH also had co-incident endometrial carcinoma. CONCLUSION: The consistency rate of endometrial tissue from curettage and hysterectomy specimens was only modest. This rate was lower in EMH without atypia. PMID- 17722315 TI - Adnexal masses in pregnancy. AB - OBJECTIVE: To determine incidence and maternal and fetal outcomes of pregnant women undergoing surgical management for adnexal mass. MATERIAL AND METHOD: A cohort study was performed in patients who presented with adnexal masses in pregnancy that required surgical management during April, 1986 to March, 2001. The maternal and fetal outcomes were analyzed. RESULTS: One hundred eighteen patients of 116,323 deliveries were identified with adnexal masses that required surgical management. The incidence was 1 in 986 deliveries. One hundred and three cases had complete data for analysis. A malignant tumor or a tumor of low malignant potential was found in 3 cases (2.9%). In 4 patients, the only finding at the time of operation were leiomyomas. Eighty-four of 103 cases (81.6%) had an elective operation and 19 cases (18.4%) had an emergency operation. There were 3 spontaneous abortions, 3 preterm deliveries, and 1 intrauterine growth restriction in all patients. Patients who underwent elective and emergency operation had the same adverse pregnancy outcome. CONCLUSION: The incidence of an adnexal mass during pregnancy in our population was consistent with what has been reported in the literature. The percentage of malignant tumors or tumors of low malignant potential was 2.9%. Patients who underwent elective operation had the same adverse pregnancy outcome compared with those who underwent emergency operation. PMID- 17722317 TI - Cervical length measurement by transvaginal sonography in preterm pregnant women for prediction of preterm birth. AB - OBJECTIVE: To determine the optimal value of cervical length and the presence of funneling in women with preterm labor to predict preterm delivery. MATERIAL AND METHOD: Transvaginal sonography to determine cervical length and presence of funneling in 69 pregnant women with gestational age between 24 - 36 weeks who had preterm labor and were admitted to the labor room of BMA Medical College and Vajira Hospital. RESULTS: The cervical length of women with preterm labor ranged between 10.7-61.2 mm (mean +/- SD = 30.1 + 9.9 mm). The prevalence of preterm delivery was 43.4%. The cervical length of 30 mm had the highest diagnostic performances in predicting preterm delivery, with the sensitivity 93.3%, specificity 82.0%. About 90% of women with funneling presence had preterm delivery. CONCLUSION: The cervical length and presence of funneling in preterm labor women are significantly associated with preterm delivery. PMID- 17722316 TI - A comparison of vaginal misoprostol 800 microg versus 400 microg for anembryonic pregnancy: a randomized comparative trial. AB - OBJECTIVE: To compare the efficacy, side effects and patient satisfaction between 800 microg versus 400 microg intravaginal misoprostol for anembryonic pregnancy. MATERIAL AND METHOD: Women who had diagnosed as anembryonic pregnancy were treated as IPD case and randomly assigned to receive either 800 microg or 400 microg intravaginal misoprostol. The second dose was administered in the equal dose if there was no evidence of abortion in 24 hr. The treatment failure was determined by no complete abortion within 48 hr. If spontaneous abortion had not occurred, or had heavy vaginal bleeding or evidence of incomplete abortion either by clinical manifestation or sonographic finding then dilatation and curettage was performed. RESULTS: Fifty patients were enrolled into the study, 25 patients were randomized to receive 800 mg and 25 patients were received 400 mg intravaginal misoprostol. Complete abortion within 48 hr was not different between the 2 groups (72%). However complete abortion within 12 hr was significantly higher in the 800 mg group than in the 400 mg group (64% versus 20%, respectively, p = 0.016). The median time to abortion in the 800 mg group was significantly shorter than in the 400 mg group (9.0 hr versus 16.0 hr, respectively, p = 0.01). There was no significant difference in the side effects and patients' satisfaction between both groups. CONCLUSION: Vaginal misoprostol can be used for termination of pregnancy in case of anembryonic pregnancy with high successful rate of complete abortion and no serious adverse effects. We recommend the 800 microg vaginal misoprostol regimen because within 12 hr the complete abortion rate was higher and the median time to abortion was shorter than the 400 microg regimen with no difference in side effects. This may decrease the suffering time of both physical and psychological trauma to the patient before complete abortion has occurred. PMID- 17722318 TI - A comparison between single dose of 50 microg oral misoprostol and 25 microg vaginal misoprostol for labor induction. AB - OBJECTIVE: To compare the efficacy and safety of a single dose of 50 microg oral misoprostol with 25 microg vaginal misoprostol for labor induction. MATERIAL AND METHOD: This study was a randomized, double-blind controlled trial conducting in pregnant women admitted at delivery room, Department of Obstetrics and Gynecology, Bangkok Metropolitan Administration Medical College and Vajira Hospital between March 2002 and January 2005. All 146 pregnancies at > or = 37 weeks' gestation who had indication for labor induction with unfavorable cervix were randomly divided into a group of single dose of 50 microg misoprostol orally or 25 microg misoprostol vaginally. Initial and six hours after misoprostol administration, Bishop scores were evaluated. Requirement of oxytocin augmentation, complication due to uterine hypertonus, incidence of vaginal delivery, Apgar score at 1 and 5 minutes, and number of neonate admitted at neonatal intensive care unit (NICU) were recorded. RESULTS: The baseline characteristics and median initial Bishop scores were comparable in both groups. At 6 hours after misoprostol administration the median cervical changes of women who received oral or vaginal misoprostol were statistically significant different, 3 and 4, respectively. The median time interval to vaginal delivery of women who received oral misoprostol was significantly longer than of those who had vaginal drug, 16.9 and 11.8 hours respectively. Comparable neonatal outcomes were found in both groups in terms of assigned Apgar score at 1 and 5 minutes. CONCLUSION: A single dose of 25 microg vaginal misoprostol appears to be more effective than 50 microg oral dose in improving Bishop scores and decreasing the time to vaginal delivery in women with unfavorable cervix without severe adverse effects. PMID- 17722319 TI - Risk indicators for cesarean section due to cephalopelvic disproportion in Lamphun hospital. AB - OBJECTIVE: To investigate risk indicators for cesarean section due to cephalopelvic disproportion. SETTING: Department of Obstetrics & Gynecology, Lamphun Hospital. DESIGN: Case-control study. MATERIAL AND METHOD: Cases were 87 pregnant women delivered by cesarean section due to cephalopelvic disproportion at Lamphun Hospital between October 1st, 2003 and June 30th, 2004. Controls were 113 pregnant women delivered by normal labour during the same period. Maternal age, gravidity, parity, maternal height, pre-pregnancy weight, gestational age, weight before delivery, weight gain, symphysis-fundal height, birthweight and newborn gender were mainly focused. Information were obtained from medical records. Groups were compared by t-test and exact probability test as appropriate. Risk indicators were analyzed by odds ratio from univariable and multiviariable logistic regression. RESULTS: Risk indicators significantly associated with cesarean section due to cephalopelvic disproportion included symphysis-fundal height greater than 35 cm. (OR = 9.38, 95% CI = 3.42-25.73); nulliparity (OR = 5.36, 95%CI = 2.24-12.82); maternal height less than 152 cm. (OR = 3.65, 95%CI = 1.63-8.17) and weight gain more than 15 kg. (OR = 2.67, 95%C1 = 1.32-5.39). CONCLUSION: Risk factors for cesarean section due to cephalopelvic disproportion included symphysis-fundal height greater than 35 cm, nulliparity, maternal height less than 152 cm. and weight gain more than 15 kg. Early detection of these risk indicators before delivery helps obstetricians and nurses to recognize potential obstructed labor and prepare for safe delivery in advance. PMID- 17722320 TI - Pregnancy induced hypertension in twin pregnancy. AB - OBJECTIVE: To compare the incidence, severity and pregnancy outcomes of pregnancy induced hypertension in twins and singleton gestations. MATERIAL AND METHOD: The cohort study enrolled 305 twins and 298 singleton gestations at Department of Obstetrics and Gynaecology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand between January 1996 and December 2001. The rates of pregnancy induced hypertension and pregnancy outcomes were statistically analysed in both groups. P-value of< 0.05 was considered statistically significant. RESULTS: Pregnancy induced hypertension was found to at develop 18.36% in the twin gestations, compared with 5.03% in the singleton gestations (P < 0.05). Women with twin gestations had higher rates of pregnancy induced hypertension (RR 3.65, 95% CI 2.11-6.30, P<0.05) and occurred earlier than singleton gestations (35.86+/-2.50 VS 37.40+/-1.18 weeks, P<0.05). Twin gestations with pregnancy induced hypertension had significantly higher rate of cesarean delivery, low birthweight, NICU admission and perinatal death than singleton gestations with pregnancy induced hypertension (P< 0.05). Moreover the abruptio placenta, postpartum hemorrhage and perinatal mortality in twin gestations with pregnancy induced hypertension group were significantly higher than in normotensive group (P< 0.05). CONCLUSION: The incidence of pregnancy induced hypertension was significant higher and occurred earlier with greater adverse pregnancy outcomes among twin gestations than singleton gestations. Moreover, the rate of adverse maternal and perinatal outcomes in twin gestations with pregnancy induced hypertensive group was higher than in normotensive group. PMID- 17722321 TI - Radical surgery for T1 and T2 squamous cell carcinoma of the vulva through separate incisions. AB - OBJECTIVES: The aim of the study was to retrospectively evaluate treatment results in patients with T1 and T2 vulvar carcinoma. MATERIAL AND METHOD: The medical records of 46 patients with T1 and T2 SCC of the vulva undergoing radical excision of the tumor and groin node dissection at Chiang Mai University Hospital between January 1998 and December 2004 were reviewed. The tumor size, histologic grade, nodal status, lymph-vascular space invasion, lesion location, surgical marginal status, complications, recurrence and survival were analyzed. RESULTS: Mean age of the 46 patients (T1 = 15, T2 = 31) was 59 years with a range of 34-84 years. The incidence of lymph node metastases for T1 lesions was 13% compared to 35% for T2 lesions. Twenty nine patients (63%) experienced surgical complications, the most common one was lymphedema (16) while wound breakdown was noted in only 1 patient. With a median follow-up of 15 months, 14 patients (30%) developed recurrence, 3 (20%) and 11 (35%) in patients with T1 and T2 lesions respectively. The overall 5-year disease-free survival and 5-year survival were 37% and 40%, respectively. The 5-year survival of patients with T1 lesion was significantly higher than that of patients with T2 lesion (64% vs 31%, P = 0.04). Patients with negative nodes had significantly better survival than those with positive nodes (56% vs 18%, P = 0.02). In multivariable analysis, only the status of groin node remained as independent prognostic factors for survival. CONCLUSION: Radical excision and groin node dissection through separate incision for T1 and T2 squamous cell carcinoma of the vulva in this study has a less favorable survival outcome compared with the literature. PMID- 17722323 TI - Role of hysteroscopy in modern gynaecology. AB - In only a few years, operative hysteroscopy has become very popular among gynecologists, whereas more than a century passed before diagnostic hysteroscopy attained wide acceptance. At present, with the development of miniaturized cameras, this endoscopic operative technique can be used in the management of all non-cancerous intrauterine lesions, with the entire procedure being performed under video monitoring. In this chapter we will review the present indications of diagnostic hysteroscopy and also report our results of hysteroscopic submucous myomectomy, polypectomy, adhesiolysis, septoplasty, and endometrial ablation. PMID- 17722322 TI - Norelgestromin/ethinyl estradiol transdermal system. AB - The transdermal contraceptive patch is an innovative contraceptive technology. The failure rate is quite low and has high continuation rate. The side effects and complications are not different from other hormonal contraceptives. This contraceptive method should be an alternative birth control technique for women. PMID- 17722324 TI - GTD 2005. PMID- 17722325 TI - Gestational trophoblastic disease in 2005. AB - Gestational trophoblastic diseases are still problematic in our practice. Event the incidence is in generally decreasing. And the development of Medicine in this decade can elucidate some parts of pathophysiology at cellular and molecular levels. However, malignant changes still can not be prevented. Approximately 20% of patients will develop malignant sequelae requiring administration of chemotherapy after evacuation of hydatidiform moles. Most patients with postmolar gestational trophoblastic disease will have non-metastatic molar proliferation or invasive moles, but gestational choriocarcinomas and metastatic disease can develop in this setting. Gestational choriocarcinoma occurs approximately 50% after term pregnancies, 25% after molar pregnancies, and the remainder after other gestational events. Although much rarer than hydatidiform moles or gestational choriocarcinomas, placental site trophoblastic tumors can develop after any type of pregnancy. For optimal management, practicing obstetrician gynecologists should be able to diagnose and manage primary molar pregnancies, diagnose and stage malignant gestational trophoblastic neoplasia, and assess risk in women with malignant gestational trophoblastic neoplasia. This chapter views some points which may be useful for evidence-based practice in modern Medicine. PMID- 17722327 TI - New approach of STI/HIV in OB-GYN. PMID- 17722326 TI - How to approach common urogynaecological problems? AB - Urogynaecology is dedicated to the treatment of women with pelvic floor dysfunction such as urinary orfecal incontinence and prolapse (bulging or falling) of the vagina, bladder and/or the uterus. Pelvic organ prolapse simply means displacement from the normal position. On average, 11% of women will undergo surgery for this condition. Pelvic organ prolapse quantification system (POP-Q) is an objective, site-specific system for describing the anatomic position that can be used to determine the stage of the prolapse. Urinary incontinence (leakage of urine) is a very common condition affecting at least 10 20% of women under age 65 and up to 56% of women over the age of 65. The most common subtypes of urinary incontinence are (1) stress urinary incontinence (SUI) ; (2) urge urinary incontinence (UUI) ; and (3) mixed urinary incontinence (MUI). Patients presenting with symptoms of pelvic organ prolapse or incontinence should undergo a thorough medical evaluation consisting of a targeted history (include bladder diary or voiding diary), physical examination, urinalysis and urine culture, and postvoid residual volume (PVRV) by pelvic ultrasound. Treatment options for patients with pelvic organ prolapse and urinary incontinence are nonsurgical (lifestyle interventions, pelvic floor muscle rehabilitation, and pessary placement) and surgical management. PMID- 17722328 TI - Fetal stem cell: from research to clinical use. AB - The discovery of new sources of stem cells over the past few years has raised the expectation that stem cells may in the future provide new biological therapies for a number of diseases, the incredible potential for substituting damaged or lacking cells, tissues, and even organs. A number of stem cell types have been identified, including bone marrow stem cells, embryonal stem cells, and fetal stem cell including umbilical cord blood (UCB) stem cells. The UCB contains a rich source of hematopoietic stem cells that can be used to reconstitute the blood system and can easily be extracted and cryopreserved, thus allowing for the establishment of HLA-typed stem cell banks. UCB have also the potential to give rise to non-hematopoietic cells, such as bone, neural and endothelial cells. PMID- 17722329 TI - LA: dialysis machine fell on dialysis nurse: workers' compensation nurse's only remedy. PMID- 17722331 TI - The International Narcotics Control Board and HIV/AIDS. PMID- 17722330 TI - The end of nandrolone. PMID- 17722332 TI - Money, moralism, and microbicides: barriers in microbicides development. PMID- 17722334 TI - Male circumcision in some nations may be the best available HIV prevention tool. Evidence growing for safety, efficacy. PMID- 17722333 TI - A rare moment in time. PMID- 17722335 TI - Aging and AIDS: special series on older patients. Experts offer this advice for improving care for older HIV patients. PMID- 17722336 TI - FDA notifications. FDA approves lipidatrophy drug. PMID- 17722337 TI - FDA notifications. FDA grants tentative approval of generic efavirenz. PMID- 17722338 TI - HIV experts discuss whether U.S. can handle influx of new HIV cases. Opt-out testing likely will cause deluge. PMID- 17722339 TI - Program's experience with using rapid HIV test proves mostly positive. State won award for program. PMID- 17722340 TI - Researchers find that Texas clinic's HIV resistance is stable over time. Clinic's population shifts to more Hispanics. PMID- 17722341 TI - FDA notifications. ESAs--serious cardiovascular complications. PMID- 17722342 TI - HIV testing guidelines meet with praise, criticism. Opponents say it violates privacy. PMID- 17722343 TI - HIV integrase inhibitors show potent activity in clinical trials. PMID- 17722344 TI - Group of journalists say PEPFAR is too inefficient and political. Money goes to favored religious organizations. PMID- 17722346 TI - U.S. HIV peer groups offer education, support to women. PMID- 17722345 TI - Patient care. Florida governor to meet AHF to address concerns. PMID- 17722347 TI - Needlestick. Claim against sharps disposal system maker dismissed. PMID- 17722348 TI - HIV legal, medical service providers launch HIV testing guide. PMID- 17722349 TI - Disclosure. Prison officials cleared of disclosing an inmate's serostatus. PMID- 17722350 TI - Treatment. Jail officials cleared of refusing HIV drugs to prisoner. PMID- 17722351 TI - SSI. Disability benefits denied blind, HIV-positive woman. PMID- 17722352 TI - Study: mentoring improves HIV-positive mom's health. PMID- 17722354 TI - Hysterectomy doesn't harm--and may help--sexual function. PMID- 17722353 TI - New cervical vaccine highly promising, but questions remain. Many experts recommend vaccinating all preteen girls. Others urge caution. PMID- 17722355 TI - Easing the pain of plantar fasciitis. To relieve heel pain, simple therapies may be all you need. PMID- 17722357 TI - By the way, doctor. What can you tell me about the mineral strontium, which is advertised for treating osteoporosis? PMID- 17722356 TI - Heart failure risk prompts warning labels on diabetes drugs. The concern now is whether this particular class of drugs causes other cardiovascular problems. PMID- 17722358 TI - By the way, doctor. If I want to lower my blood pressure, how much salt can I afford to take? PMID- 17722359 TI - Although many of the items are natural products, we do not know what harm they might cause in the often excessive quantities that are recommended. PMID- 17722360 TI - So you want to be an editor-in-chief... PMID- 17722361 TI - Misdiagnosis of pulmonary bulla. PMID- 17722362 TI - Recent initiatives for radiation oncology resident education in radiation and cancer biology. AB - Nearly all residents from accredited radiation oncology residency programs in the United States are required to take the American College of Radiology (ACR) In Training examination each year. The test is comprised of three sections: Clinical Radiation Oncology, Radiological Physics, and Radiation (and Cancer) Biology. Here we provide an update on changes to the biology portion of the ACR exam. We also discuss the availability and use of the ACR and biology practice exams as assessment and teaching tools for both the instructors of radiation and cancer biology and the residents they teach. PMID- 17722364 TI - The Beothuk on the eve of their extinction. PMID- 17722363 TI - Charred, non-maize seed concentrations in the American Bottom area: examples from the Westpark Site (11-MO-96), Monroe County, Illinois. PMID- 17722366 TI - The Endocrine Society 2007 Laureate Awards. PMID- 17722365 TI - The Endocrine Society Laureate Awards. PMID- 17722367 TI - Plasma endothelin-1 levels in septic patients. AB - Dysfunction of the vascular endothelium (ET) causes an increase in serum ET-1 concentration, as observed in septic patients. It was assumed that in this patient population the ET-1 level correlates with the degree of sepsis severity, including the level of organ dysfunction and, in particular, the level of circulatory dysfunction. The aim of the present study was to assess the relationship between levels of ET-1 and levels of N-terminal brain natriuretic propeptide (NT-proBNP), procalcitonin (PCT), and C-reactive protein (CRP), as well as the Sepsis-related Organ Failure Assessment (SOFA) score in septic patients. PCT and CRP were used to estimate the level of sepsis severity; the SOFA score was used to estimate multiorgan dysfunction; and NT-proBNP was used as a marker of cardiac dysfunction. Twenty patients with sepsis and severe sepsis were included in the study. Blood serum ET-1, NT-proBNP, PCT, and CRP concentrations were determined at specific time intervals, and the SOFA score was calculated. Mean ET-1, NT-proBNP, PCT, and CRP concentrations were 8.39 pg/ml +/- 6.39 pg/mL, 140.80 pg/mL +/- 84.65 pg/mL, 22.32 ng/mL +/- 97.41 ng/mL, and 128.51 mg/L +/- 79.05 mg/L, respectively. Correlation between ET-1 levels and levels of NT-proBNP, PCT, and CRP was .3879 (P < .001), .358 (P < .001), and .225 (P = .011), respectively. Mean SOFA score was 6.31 pts +/- 3.75 pts. Correlation between the ET-1 levels and SOFA score was .470 (P < .001). Six patients (30%) died during the observation period of 28 days. ET-1 levels correlate with levels of NT-proBNP, PCT, and CRP, as well as the SOFA score in septic patients. PMID- 17722369 TI - "I saw all that": a Lakota girl's puberty ceremony. PMID- 17722368 TI - Continuous venovenous hemodiafiltration for life-threatening mitochondrial myopathy with lactic acidosis and rhabdomyolysis. AB - We report here the clinical course of a 31-year-old male who recovered from a fulminant form of mitochondrial myopathy with lactic acidosis. The patient was transferred to our hospital with acute dyspnea and a convulsive seizure. On admission, he was in a state of shock, and presented with severe high-output heart failure, acute renal failure, and rhabdomyolysis. Treatment with continuous venovenous hemodiafiltration (CVVHDF) resulted in an excellent response, with no signs of hemodynamic instability. This case suggests that CVVHDF with serial hemodynamic monitoring may be effective in treating hypotensive patients with a life-threatening mitochondrial disorder. PMID- 17722370 TI - Pharmaceutical aphrodisia. PMID- 17722371 TI - Two schools of desire: nature and marriage in seventeenth-century Puritanism. PMID- 17722372 TI - Portrait prints of men of science in eighteenth-century America. PMID- 17722373 TI - Social investment in medical forms: the 1866 cholera scare and beyond. PMID- 17722374 TI - A crucible of contradictions: historical roots of violence against children in the United States. PMID- 17722375 TI - Environmental enemies: environmental factors may be causing many chronic diseases. Tracking the link between them helps. PMID- 17722376 TI - Death and dying: old themes and new directions. PMID- 17722377 TI - In the hands of the British: the treatment of American POWs during the War of Independence. PMID- 17722379 TI - Interpreting the latrines of the Johnson's Island Civil War military prison. PMID- 17722378 TI - Family and marriage of late-nineteenth and early-twentieth-century immigrant women. PMID- 17722381 TI - Advances in mental health and their reflections in nursing. PMID- 17722380 TI - Victoria Woodhull, Anthony Comstock, and conflict over sex in the United States in the 1870s. PMID- 17722383 TI - [Reuse of discarded syringes in residences of children and teenagers with diabetes mellitus]. AB - Inadequate or insufficient supply of medication and material to apply insulin leads families to resort to a variety of strategies, such as the practice of reusing dischargeable syringes in order to reduce the expenses with the illness. This is a study aimed at evaluating the practice of insulin application, analyzing the practice of syringe reuse and describing the most frequent changes of application sites. It is a comparative, transversal survey carried out with 199 diabetic children and adolescents. It was developed at the diabetes' Outpatient Unit of the Hospital das Clinicas' Child Institute, of the University of Sao Paulo's School of Medicine. The studied population was divided in two groups: in Group A were those who reused the syringes, and in Group B those who did not. A common strategy was rewrapping the needle without previously cleaning it and keeping it inside or outside the refrigerator in a closed container. The most common complaint was pain. The hospital and the nurse were responsible for the orientation for that practice. PMID- 17722382 TI - [Knowledge, attitudes and behaviours about AIDS in Portuguese adolescents in urban and non-urban environment]. AB - The main objective of this investigation was to identify and compare preventive knowledge, attitudes and behaviors regarding AIDS between adolescents at the secondary school in urban and non-urban areas in Portugal. This is a descriptive study with a sample of 826 individuals (455 adolescents from urban environment and 371 from a non-urban environment). The instrument for data collection adopted was based on the Health Belief Model conceptual model. It was recognized that there is a relation between the environment insertion of the adolescents and the recognition of AIDS as a serious threat, and the knowledge about the risks of infection with AIDS and the attitudes towards AIDS. PMID- 17722384 TI - [Hypertension associated factors and blood pressure among adolescent workers]. AB - The aim of this study was to identify hypertension associated factors (AF) and verify blood pressure (BP) levels among adolescent workers. Interviews were conducted with 193 working adolescents--135 men and 58 women between 16 and 18 years. After five minutes in seated position, their arm circumferences were measured and their BP was determined using correct (CCW) and standard (SCW) cuff widths. The values were related to AF. BP was, in average, 105.2/60.9 mmHg (CCW) and 101.0/57.9 (SCW- p < 0.05). Among the AF found, only skin color and alcoholic drinking were associated to BP elevation, also noted in male adolescents. When using CCW, more hypertensive and borderline adolescents were found than using SCW. All of them had at least one AF. It can be concluded that there are several hypertension AF among this population, and some of them are already causing BP elevation. Studies such as this should be made frequently because adolescent blood pressure levels can predict hypertension in adulthood. PMID- 17722385 TI - [Parents and caregivers of depressed adolescents: learning about experiences that led to the search for specialized care]. AB - This study is aimed at analyzing the processes and the motivations that lead parents and caregivers to notice the depressive illness in adolescents and at understanding the influence of health beliefs and cultural habits in the search of specialized treatment. Using the qualitative case study method, four parents and/or caregivers of adolescents with diagnoses of depression under treatment at a mental health clinic in the city of Campinas, State of Sao Paulo, were interviewed. In accordance with the theoretical presumptions of the Health Belief Model (HBM), the categories that were created and discussed were: the perception of parents and caregivers regarding the susceptibility to the depressive illness; the perception of parents and caregivers regarding the severity of the depressive illness; external stimuli influencing the search for specialized treatment; the barriers and benefits perceived for the search for specialized attendance; structural and social variables influencing the search for specialized attendance. PMID- 17722386 TI - [Mothers under suspicion: talking about school age children's health]. AB - This study has as its objective to explain the assistance to the school age child's health under the light of historic and dialectic materialism, including gender for the social approach. The results regarding the interviewees' representations (health professionals, teachers and mothers) revealed that the conceptions about the health-illness process of school pupils are highly biologicist, even though there were-- but in a much smaller scale--references to its psychic and social dimensions. The data analysis, according to the feminist theory, shows that the idea of gender inferiority is the origin of the biased conceptions regarding the mothers of the studied children. Such prejudices were observed in the three locations studied (heath service, school and family). PMID- 17722387 TI - [Investigation of the related factors between newborn history and red reflex]. AB - The red reflex test is an important part of the newborn's ocular exam. This study investigated the relationship between red reflex in premature newborns (PN) and factors of the newborn history. It's a descriptive, exploratory, quantitative study conducted in a public maternity in Fortaleza, State of Ceara, with 114 PN between the months of April and May of 2004. For data registration was used a questionnaire, and for the ocular exam a direct ophthalmoscope. Data showed the following findings: 68% of PN had an Apgar under seven during the first minute; 112 were submitted to oxygen therapy; and 68 to phototherapy. As for the red reflex, 13 (11%) showed alterations, with significant statistical association between red reflex and the Apgar during the first minute of life (p = 0.041). The results cause concern because 10 of the 13 PN with red reflex showed retinopathy of prematurity. PMID- 17722388 TI - [Looking for a nursing home for an elderly person: reasons appointed by relatives]. AB - This study, conceived in order to try to understand the situations that motivate families to place elderly relatives in nursing homes, used a methodological qualitative approach. Data collection was conducted through open interviews. The analysis of the answers resulted in two categories: the placement in a nursing home as a way to meet the elder person's needs; and the search for the best place for the elder to live and keep the bond with the family. Living through the process of placing an elder relative in a nursing home constituted a transition period in which different factors were taken into account and contributed for the decision. When this decision is taken, the family looks for the best place in terms of physical structure, care and social living, with equals and with other people, because it is believed that through visits family and affective bonds can be kept. PMID- 17722389 TI - [Aging and work ability of workers of a university hospital's cleaning and hygiene service]. AB - This study was conducted with the cleaning personnel of a university hospital in the city of Campinas, State of Sao Paulo. These are public employees whose work is mainly physical: cleaning is a job that requires heavy physical work; in addition, workers are also exposed to chemical products. The objective of this survey was to evaluate the work ability of cleaners from different age groups, for which was used the Work Ability Index, an instrument developed by Finnish researchers. The sample was comprised of 69 workers who answered the questionnaire: 21.7% have excellent work ability; 31.9% good; 31.9% moderate; and 14.5% poor. The most frequently reported diseases with medical diagnosis were: lesion due to accidents, musculoskeletal disorders, and cardiovascular diseases. The members of the older group ranked lower in the Work Ability Index and reported a larger number of diseases, which therefore affected their work ability. PMID- 17722390 TI - [Health education to ostomy patients: a bibliometrics study]. AB - This study has as its objective to identify the scientific studies dealing with the orientation to patients submitted to ostomy published between 1970 to 2004 and to classify them according to quantity, chronology of publication, authors' function, source, kind of study, topic, origin and key words by using the bibliometrics methodology. A total of 27 publications were collected in the DEDALUS databank, in the LILACS and MEDLINE databases and from a professor of the University of Sao Paulo's Nursing School (EEUSP, which is a national reference in ostomy in Brazil). Of these, 19 were written by Brazilians and 8 by non Brazilians; most were written by nurses and enterostomal therapists. Dissertations, theses, orientation manuals, books and articles were found. The origin of the material was academia, laboratories and hospitals. The 1990s concentrated the largest number of studies in this thematic area. All of them have the purpose of elevating patients' self-esteem in order to make them feel that, even with an ostomy, they can have a normal life. Thus the study concludes that the nurse, as an educator for the ostomy patient, should be acquainted with those publications to improve the assistance he/she provides. PMID- 17722391 TI - [Daily life of schizofrenia patients after the use of clozapine and group follow up]. AB - This study was carried out with a sample of 11 patients who are part of the atypical medication group at the Hospital das Clinicas of the University of Sao Paulo at Ribeirao Preto's School of Medicine. For data collection semi-structured interviews guided by a script were held in April 2003. The interviews were first taped and fully transcribed afterwards. Results indicated an improvement in patients' symptoms, demonstrated by decreased social isolation, resumption of home/work activities and studies, as well as by participation in social events. They also point out to the need for a new vision regarding patients who suffer from mental disorders and their family members in the sense of searching for adequate therapeutic attitudes that have an impact on the production of life, aimed at giving a new existential meaning in the different forms of social contact and sociability. PMID- 17722392 TI - [Surgical site infection in a university hospital: post-release surveillance and risk factors]. AB - The aim of this study was to determine the incidence of the Surgical Site Infection (SSI) in the hospital and after discharge in patients submitted to digestive system surgeries (SDS), and to verify the association between SSI and the type of surgery, the time of hospital internment, the patient's clinical condition, the classification of the surgical wound and the duration of the surgical procedure. It is a prospective study carried out at a university hospital between August of 2001 and March of 2002. Of 357 patients submitted to SDS, 64 SSI cases were notified--16 in the hospital and 48 after discharge, incidences of 4.5% and 13.9% respectively. It was verified an association of SSI with the preoperative stay in hospital and with the classification of the surgical wound. The global incidence of SSI was 18.0%, and there was a four-fold increase when the post-discharge surveillance was carried out. In consequence, it can be concluded that if the post-discharge surveillance is not conducted the global SSI incidence would be strongly undernotified. PMID- 17722394 TI - [Computer-mediated teaching of didactics in nursing: students evaluation]. AB - This exploratory descriptive study's purpose is to describe what students think regarding the form and content of an educational site and its application as an instructional resource for the discipline of Didactics in Nursing in the undergraduate course in Nursing at a school in the city of Sao Paulo. The study's subjects were students enrolled in that discipline during the first semester of the school year of 2003. The results show promptness regarding the use of computers on the part of the students, who are favorable to the adoption of new computer-mediated teaching methodologies in Nursing as a means to increase and diversify the forms of communication between instructors and students. PMID- 17722393 TI - [Productivity indicators in a sterilization central supply]. AB - This study identifies productivity indicators at a Sterilization Central Supply (CME) through documents, observation and time counting of the process for two items selected from the sample: a bandage pack and a herniorrhaphy box. The monthly average production was 30,466.42 items, and the production capacity per hour was 10.3 items per employee. The bandage pack averaged 295 minutes from the expurgation area to storage; the manual process lasted 46 minutes and the automated 88 minutes. For the herniorrhaphy box the average was 329 minutes; the manual process lasted 60 minutes and automated 98 minutes. In the bandage kit, the manual process used up 59.23% of the productivity hours in the expurgation area, 3.28% in the preparation, 10.94% in the sterilization process, and 26.31% in storage and distribution. Figures for the manual process of herniorrhaphy box were: expurgation, 11.84%; preparation, 16.20%; storage and distribution, 7.47%; and sterilization, 1.89%. The study made possible to assess the results and to analyze the working process at the CME. PMID- 17722395 TI - [High school and professional education in nursing: some reflections]. AB - Analyzing the politics of professional education and questioning the changes that have been introduced in the Brazilian high school system are the main objectives of this study. In general, the approved legislation expresses the interests of the neo-liberal policies, of multilateral organisms, and of the implications of the worldwide productive reorganization and of the reduction of State participation in social policies. It also mirrors the manner in which Brazil inserts itself in the globalization process, in a dependent role, more as a knowledge consumer than a producer of it, thus missing the opportunity for achieving its autonomy, including in the area of professional formation. Based on the possibilities that these laws offer for curricular organization, this article defends that professional teaching in Nursing should take up a technical perspective integrated to a general education and be provided in a single space, thus reducing the risk of a minimalist, superficial training. PMID- 17722396 TI - [Female nurses and the osteomuscular disturbances related to their work]. AB - This study investigates the relation between female nurses and osteomuscular disturbances associated with their work. It is clear from the study that Nursing professionals are exposed to a number of unfavorable conditions in their working environment. Predominant complaints are related to the osteomuscular system, which affects mostly females due not only to the biological characteristics of women, but also because of the uneven distribution of work between genders that prevails nowadays. PMID- 17722397 TI - [Scientific production of Brazilian nurses on blood pressure measurement]. AB - In the previous issue of this journal the authors celebrated in an article the discovery of the Korotkoff sounds, in 1905, and presented the historical facts that determined the important role of the University of Sao Paulo's Nursing School (EEUSP) in the development of the oldest blood pressure research line in Brazilian Nursing: "Cuff Width Influence in Blood Pressure Measurement." This new article presents the scientific production derived from the studies carried out by nurses with a PhD from EEUSP during and after their doctoral programs in the area. The path each researcher followed in his/her group and laboratory is emphasized. The data presented is aimed at offering a number of qualitative and quantitative indicators that make possible to evaluate the impact of the research that they have carried out, as well as the development of knowledge in the area. PMID- 17722398 TI - [Immunization control and student registration at the city of Sao Paulo's Municipal Schools of Infantile Education]. AB - The presentation of the vaccination passbook is mandatory for student registration at the city of Sao Paulo's Municipal Schools of Infantile Education, as a form of stimulating parents to keep their children's immunizations calendar updated. However, attendants do not verify periodically if the vaccinations are correct. In order to overcome this problem, a project with the aim of facilitating the immunization control through a software that controls immunizations was tested at a Municipal School of Infantile Education. Of the 286 pupils registered in the system, 236 (82.5%) were notified that their vaccines were incomplete. Of these, 21.2% updated their vaccinations, 2.5% returned their passbooks unchanged, and the remainders were still in the process of updating. The program identified the imperfections and encouraged immunization, thus helping to prevent the propagation of transmissible diseases in the school environment. PMID- 17722399 TI - [Teaching surveillance to workers' health in nursing courses]. AB - The objective of this study is to describe the experience at the Federal University of Sao Carlos concerning the mandatory discipline Nursing and Workers' Health, taught at the undergraduate course in Nursing, which focuses on the activities that concern workers' health surveillance. As a teaching strategy, an epidemiological analysis of all labor accidents registered at the local agency of the social security system referring to the municipality of Sao Carlos, State of Sao Paulo, in the year of 2000 was carried out. Based on this information system the students developed practical activities related to the organization of the data and the use of the software to insert, consolidate and analyze the information. Besides this, themes concerning workers' health surveillance and related issues have been developed. The results obtained in these activities have been evaluated and are discussed in this article. PMID- 17722400 TI - [Feelings and experiences in women with breast cancer's life]. AB - Identifying feelings and experiences related to breast cancer becomes important to enable those who are part of a woman's social circle to grasp this stage of her life. For this study, a literature review was carried out in order to identify what are the most common thoughts and feelings women experience after a breast cancer diagnosis. The review was conducted through bibliographical research in LILACS and MEDLINE databases using the key words breast, cancer, feeling, female, and representation. Contents related to cancer were searched, such as the meaning of the disease and its implication to the woman's emotional and social life. The conclusion was that experiences related to breast cancer have an individual scope, and that their representations are different for each woman. PMID- 17722401 TI - [Katz Index on elderly functionality evaluation]. AB - The growing number of the elders has been increasing the need for the use of functional evaluation instruments. But such use should be done in such a way as to allow comparisons among the various studies and the different realities. Among those instruments, the Index of Activities of Daily Living (ADL), developed by Sidney Katz, is one of the oldest and one of the most frequently mentioned in Brazilian and international literature. Different articles have been showing, however, modified versions of that instrument, thus making it difficult for readers to correctly use it. This paper has the objective of making a historical account of the development, evolution and correct use of Sidney Katz's Index of Independency in the Daily Living, as well as the changes and adaptations it has gone through time, with the author's agreement, so as to contribute for the standardization of the research information related to functional evaluation in gerontology. PMID- 17722402 TI - ED physicians group ousted, sues--power struggle with CEO blamed. AB - Serious contract problems with administration should never come as a surprise. The ED manager who is part of a physicians group should communicate regularly with key audiences within the hospital, and keep an ear to the ground for potential issues. Have routine meetings with senior administration, and work to gain a seat on the hospital's executive committee. Participate in community activities with hospital leadership, including family activities. Work to develop a professional working relationship with the nurse manager. PMID- 17722403 TI - What surveyors want to see for review of med orders. AB - The Joint Commission has suspended its interim action allowing pharmacists to retrospectively review ED medication orders, but it is allowing broader interpretation of the exceptions to the requirement for prospective review. The medication can be processed by a nurse, and the licensed independent practitioner (LIP) will not be required to remain at the bedside while the medication is administered. The LIP must remain available to provide immediate intervention in the event that the patient experiences an adverse medication event. The LIP will be allowed to define when a clinical situation is urgent. PMID- 17722404 TI - Fever kit helps ED save $300,000 in three years. AB - A fever kit is easy and inexpensive to assemble, and it's an effective strategy for reducing unnecessary ED visits. Be sure the kit includes a digital thermometer, a supply of children's acetaminophen, an oral syringe to measure doses, and dosing instructions (also in Spanish if needed). Make sure discharge instructions are not only written, but also verbal. Make sure parents understand how to use the thermometer and measure the proper dosage. Have clear protocols outlining who should receive the kits and for which conditions. PMID- 17722405 TI - 'Boarded' patients prefer halls on inpatient floors. AB - If you can board patients upstairs rather than in your ED, not only will you free space in your department, but you will be giving patients what they want, based on the results of a recent study. Because this change involves other units, buy in must be obtained from administration. You can make a case with administration based not only on improved safety and care, but also on patient satisfaction. Initial costs for boarding patients in inpatient halls will be higher because additional staff will be needed, but these can be offset by reducing the number of patients who leave without being seen. Spreading care over several units will relieve the pressure on ED nurses. PMID- 17722406 TI - Social workers cut nonemergent visits 45%. AB - Having a social worker in your ED to identify patients who are seeking primary care can significantly limit return nonemergent visits. ED staff who have interfaced with a social worker find it doesn't interfere with their normal work flow. Invite the social workers to staff meetings before they begin working in your department to familiarize staff with what the social workers will do. Make sure the social workers are well versed in EMTALA so they do not turn patients away from the ED. If the social worker does not approach the patient until treatment is completed, smooth flow in the department is ensured. PMID- 17722407 TI - Discharging the homeless--crisis in 'La-La Land'. PMID- 17722408 TI - Nutritional status and intelligence quotient of primary schoolchildren in Akure community of Ondo State, Nigeria. AB - A cross-sectional survey was conducted among 402 children (10-15 years) randomly selected from twelve public and private primary schools in Akure community of Ondo State, Nigeria. Self-administered questionnaire was used to collect information on children's demographic features and parent's socio-economic characteristics. The subject's weight, height, height-for-age and weight-for height z-score were measured and determined respectively. Raven Standard Progressive Matrices consisted of 60 questions was administered in a quiet classroom within 60 minutes to assess intelligence quotient (IQ) of the children. The means of measured parameters were: age, 11.5 +/- 0.08 years; weight, 33.3 +/- 0.35 kg; height, 1.4 +/- 0.0 m; height-for-age z-score, -0.003 +/- 0.04; weight for-height z-score -7.2E-7 +/- 0.1 and IQ, 20.9 +/- 0.56 (34.8%). The occupations of the children's parents were civil service (43.3%), petty business (21.9%), farming (15.8%), vocational jobs (16.0%) and none (3.2%). The majority of the parents (31.8%) had secondary school education. Parents with no formal education, primary education, tertiary education and higher degrees accounted for 7.2%, 30.6%, 22.9% and 7.4%, respectively. Monthly incomes ranged between $38.5 and 230.8. Weight-for-height z-score of the children showed that 49.8% were normal, 40% mildly wasted, 9.7% moderately wasted and 0.5% severely wasted. Height-for age z-score was 50% normal, 35.1% mildly stunted, 13.4% moderately stunted and 1.5% severely stunted. IQ scores were 5% superior 11.2% above average, 11.4% average, 8.2% below average and 64.2% intellectual deficit. The interrelationship between height-for-age, IQ and socio-demographic characteristics showed that there were insignificant differences between the age groups, gender and socio economic status of the pupils. Conclusively, this study showed that the proportion of malnourished and intellectual deficit among the studied population were high. However, it is not clear whether the findings are specific to the studied population alone or applicable to other parts of Nigeria. Further studies are therefore needed to confirm these findings. PMID- 17722409 TI - Effect of germination of finger millet on nutritional value of foods and effect of food supplement on nutrition and anaemia status in Tanzanian children. AB - Inadequate dietary intake, often combined with an infection can lead to malnutrition that often manifest as growth failure or deficiency of essentials nutrients including iron leading to iron deficiency anaemia. In an effort to investigate diet in relation to nutrition status of children, diet and dietary intake were investigated in rural Tanzania. The effect of germination of finger millet based food recipe on its nutritional value was evaluated. The food consisted of finger millet flour, kidney beans, ground peanuts and dried mangoes at predetermined proportions of 75:10:10:5 respectively. Dietary habits of young children were investigated and effects of a fortified food supplement and the cereal based recipe on nutrition status of children were investigated. The two diets were then supplemented to children for 6 months and changes on anaemia and anthropometrical indices of children were evaluated at follow up periods. To assess anaemia and iron status, haemoglobin (Hb), haematocrit (Hct), erythrocyte protoporphyrin (EP) and serum ferritin (SF); and weights and heights were measured to assess growth. A significant improvement in nutrient density was noted in processed cereals. Bioavailability of iron in cereal based diet increased from 0.75 +/- 18 to 1.25 +/- 41 mg/100 g (P = 008), viscosity was significantly raised by 12% and phytate concentration was reduced from 4.5 +/- 0.5 to 4.1 +/- 0.5 mg/g (P = 0.03). Significantly lower intake of iron was observed in schoolchildren with Hb < 11.5 g/dl) compared to those who were normal. Total iron intake was 22+/- 7 and 27 +/- 13 mg/day, respectively (P < 0.05). There was a significant correlation between iron intake and serum ferritin (r = 0.233, P < 0.05). After six months of supplementing children with the fortified beverage a significantly larger increase in haemoglobin concentration was shown in the fortified group than in the non-fortified group (a difference of 6.2 versus 3.2 g/dl respectively). Supplementing infants with the germinated cereal based food supplement showed a general improvement on Hb status and growth that was not significantly different to that in the control group (P > 0.05). In conclusion, consumption of foods with low iron bioavailability is a major cause of anaemia. Germination improves the nutritional value of foods however there is need to fortify such processed foods for infant feeding. PMID- 17722410 TI - Improved microscopy diagnosis of pulmonary tuberculosis using sodium hypochlorite concentration technique in Tanga, Tanzania. AB - Pulmonary tuberculosis diagnosis commonly relies on the bacteriological examination of sputum. A cross-sectional hospital-based study was carried out to compare on "on the spot" sputum staining using sodium hypochlorite (bleach method) and routine Ziel-Neelsen (ZN) staining technique. Study candidates included individual patients presenting with cough <3 weeks (Group I) and > or =3 weeks (Group II). Sensitivity and specificity of the bleach method was calculated and compared at 100% using the ZN staining technique as the standard. A total of 171 patients (94 males, 77 females) with mean age 34.9 years (SD +/- 12.9) were recruited. Fifty-eight patients had coughed for <3 weeks while 113 had coughed for 23 weeks. Smear-positive TB in Group I was 13.8% (95% CI = 5-23) while in Group II was 25.7% (95% CI = 21-29). Using the bleach method, the prevalence of smear-positive TB in Group II was 28.3% (CI 95% = 20-36). This was an increase in smear-positivity rate of 15.6% as compared to the ZN technique. These results suggest that the use of bleach technique "on the spot" improve the sensitivity of tuberculosis diagnosis among patients with a history of coughing of over three weeks. However, further studies in different settings are recommended to validate the technique. PMID- 17722411 TI - Where do tuberculosis patients go for treatment before reporting to DOTS clinics in southern Nigeria? AB - Health-seeking patterns of persons with tuberculosis (TB) before reporting at the Directly Observed Treatment Short-course (DOTS) clinic for diagnosis and treatment were analysed. A total of 221 persons registered in the DOTS programme in 12 randomly selected rural and urban Local Government Areas in southern Nigeria were interviewed using a semi-structured questionnaire. Perceived causes of TB influenced first choice of treatment. Patients re-evaluated initial choices and shop for alternatives in persistent TB. Chemists were the first port of call for most patients. Those with unscientific causative theories of tuberculosis such as witchcraft engaged more in multiple health-seeking than those who indicated bacterial infection (P < 0.0001). The respondents had a median diagnostic-delay of 90 days. Delay in commencement of DOTS treatment was attributable to ignorance among patients and poor attitude of health workers. In conclusion, delay exists between recognition of symptoms and initiation of treatment in DOTS clinics partly because of ignorance among patients. Health workers' attitude to patients reporting at health clinics also discouraged the use of DOTS facilities. Consequently, it is recommended to address such delay through social mobilization of communities and through engaging Chemists in TB service delivery in this area. PMID- 17722413 TI - Assessment of quality assurance in HIV testing in health facilities in Lake Victoria zone, Tanzania. AB - Tanzania is currently implementing the antiretroviral treatment programme, and has a target of putting about 400,000 eligible HIV infected individuals on treatment by 2008. This will involve screening a large number of people, which will require non-laboratory personnel to be involved in doing HIV testing. In order to guarantee reliable and quality HIV test results, there is a need to ensure that quality assurance (QA) procedures are followed from specimen collection, testing and reporting of results. In light of the above a survey was conducted to assess QA in HIV testing in health facilities in Lake Victoria zone, Tanzania. A total of 89 health facilities (29 hospitals, 34 health centres, 9 dispensaries and 17 voluntary and counselling testing centres) were surveyed. Only three (10.3%) health facilities reported performing Uniform II ELISA for HIV diagnosis. All other health facilities reported to be using HIV rapid tests Capillus and Determine. Five (5.6%) of health facility laboratories performed CD4 counts. Internal quality control (IQC) were performed in 21 (63.6%) of the hospitals. Kits for HIV testing were reported to be readily available by 54 (60.7%) of the facilities. Only 16 (18%) of the health facilities had standard operating procedures in place. Systems of equipment calibration were reported by 13 (14.6%) of the health facilities. Counselling services were available in all health facilities and all counsellors had received the 6-week mandatory training course. These findings show that most of health facilities in the Lake Victoria zone do not adhere to QA procedures in HIV testing. There is therefore, a need to establish a monitoring system to laboratories performing HIV testing for the purpose of ensuring QA procedures are done. Personnel doing HIV testing should be re-trained at a regular basis to cope with new techniques and ensure QA procedures are followed. PMID- 17722412 TI - The vulnerability of orphans in Thyolo District, southern Malawi. AB - It is estimated that Malawi has about 900,000 orphans, the majority of whom are orphaned as a result of AIDS. Orphans in rural areas are mostly neglected by economic and social empowerment initiatives. This study was conducted to explore the living situation of orphans in rural Thyolo District, southern Malawi. Qualitative methodology was used in data collection and analysis to explore orphan children's living situation and specifically with regard to access to health care, education, food and basic needs. In addition, issues of love and companionship, discrimination and the future. Twenty-three orphan children and four adults were interviewed. The children reported experience with lack of food, school drop out and truancy, lack of social support to obtain present needs and prepare for the future. Public health programs aimed to prevent and mitigate the effects of AIDS in Malawi should be tailored to provide support to orphan children. PMID- 17722414 TI - Traditional health practitioner and the scientist: bridging the gap in contemporary health research in Tanzania. AB - Traditional health practitioners (THPs) and their role in traditional medicine health care system are worldwide acknowledged. Trend in the use of Traditional medicine (TRM) and Alternative or Complementary medicine (CAM) is increasing due to epidemics like HIV/AIDS, malaria, tuberculosis and other diseases like cancer. Despite the wide use of TRM, genuine concern from the public and scientists/biomedical heath practitioners (BHP) on efficacy, safety and quality of TRM has been raised. While appreciating and promoting the use of TRM, the World Health Organization (WHO), and WHO/Afro, in response to the registered challenges has worked modalities to be adopted by Member States as a way to addressing these concerns. Gradually, through the WHO strategy, TRM policy and legal framework has been adopted in most of the Member States in order to accommodate sustainable collaboration between THPs and the scientist/BHP. Research protocols on how to evaluate traditional medicines for safety and efficacy for priority diseases in Africa have been formulated. Creation of close working relationship between practitioners of both health care systems is strongly recommended so as to revamp trust among each other and help to access information and knowledge from both sides through appropriate modalities. In Tanzania, gaps that exist between THPs and scientists/BHP in health research have been addressed through recognition of THPs among stakeholders in the country's health sector as stipulated in the National Health Policy, the Policy and Act of TRM and CAM. Parallel to that, several research institutions in TRM collaborating with THPs are operating. Various programmed research projects in TRM that has involved THPs and other stakeholders are ongoing, aiming at complementing the two health care systems. This paper discusses global, regional and national perspectives of TRM development and efforts that have so far been directed towards bridging the gap between THPs and scientist/BHP in contemporary health research in Tanzania. PMID- 17722415 TI - The effect of mastectomy and radiotherapy for breast carcinoma on soft tissues of the shoulder and its joint mobility among Egyptian patients. AB - Patients with post mastectomy soft tissue shoulder disorders usually benefit from various lines of physiotherapy treatment. However, the controversy about their efficacy persists. The aim of this work was to study and assess the efficacy of each, and to identify the best intervention. One hundred female patients with ipsilateral post mastectomy shoulder problems were enrolled in the study, from September 2003 until December 2004. They were followed up for 32 weeks. Mastectomy, both radical and conservative and axillary lymph node clearance, was the standard surgery applied for operable breast carcinoma in this series. Clinical examination was followed by testing for the shoulder complaint by measuring maximal protrusion at the inferior scapular angle, scapular stabilization and the lift-off tests. Approved physiotherapy modalities were then applied, viz: no treatment (randomly chosen 12 patients), passive and active motion therapy (14 patients), oral diclofenac sodium (19 patients), local triamcinilone injection (40 patients) and manually applied low intensity laser therapy (15 patients). Assessment was by determining overall success rate for each intervention modality. Intervention outcome was assessed at 8, 16, and 32 weeks as shown by physical examination using the healthy shoulder as a reference, and by measuring restricted mobility during passive lateral rotation and glenohumeral abduction. "Success rate" was determined separately for each group at the end of the intervention period. The applied surgery was followed by radiotherapy in 96%, chemotherapy in 24% and both in 11%. The presenting post mastectomy symptoms at the shoulder were pain (100%), shoulder weakness (88%), winging of the scapula (11%) and inability to perform everyday shoulder movements (23%). Evaluation was by overall improvement score. The results were: 14.3% for untreated patients, 43.3% for those treated by motion therapy, 42% for diclofenac therapy, 80.7% for local triamcinolone, and lastly 68% for low intensity laser therapy. All treatment regimens for shoulder disabilities in those patients gave little long-term advantage, local steroid injections were the most effective. Low level laser therapy may augment its effect. It is concluded that all treatment regimens provide little long-term advantage; however, trimcinilone local injections may be the most useful in terms of pain relief and improvement in shoulder movement. PMID- 17722416 TI - Prevalence of blindness and visual impairment in Atakunmosa West Local Government area of southwestern Nigeria. AB - Blindness survey remains a useful tool for eye care needs assessment. A cross sectional survey of Atakunmosa West Local Government Area, a rural community of southwest Nigeria with no form of eye care facility was carried out. The objective of this study was to define areas of eye care need and develop programme for elimination of avoidable blindness in the region. Multistage cluster sampling technique selected 1248 respondents across all the eleven health districts. Respondents had visual acuity and ocular examination. Blindness was defined as presenting visual acuity (pva) of < 3/60 in the better eye and visual impairment as pva of < 6/18 in the better eye. Out of the 1,248 respondents screened, 14 (1.1%) were blind and 78 (6.3%) were visually impaired. There was an increasing risk of blindness and visual impairment with age; occurring more commonly after 60 years of age. The prevalence of blindness and visual impairment were higher in females although not statistically significant (P = 0.70; 0.46 respectively). Blindness was caused mainly by cataract (57.2%), glaucoma (14.3%) and congenital childhood blindness (14.3%). Cataract (57.7%), glaucoma (16.7%) and uncorrected refractive error (15.4%) were the leading causes of visual impairment. Blindness was avoidable in 85.7% of cases. Qualitative and subsidised cataract surgical and refractive services are needed urgently in this region and therefore, the incorporation of eye health care into the existing primary health care system may ensure programme sustainability. PMID- 17722417 TI - Cardiac risk indices of staff of Federal University Of Technology Owerri, Imo State, Nigeria. AB - Non-communicable diseases are the major health burden in the industrialized countries and are increasing rapidly in the developing countries owing to demographic transitions and changing lifestyles among the people. Cardiovascular diseases (CVD) are increasingly becoming a great cause of morbidity and mortality. A total of 100 senior and 141 junior staff in Federal University of Technology, Owerri (FUTO), Imo State, Nigeria was randomly selected for a study on cardiac risk factors. A questionnaire was used to record cardiac risk indices like age, heredity, body mass index (BMI), tobacco smoking, exercise, serum cholesterol estimation, systolic blood pressure and sex. There was no significant difference between the senior and junior staff in sex distribution (P = 0.71), family history of CVD (P = 0.34), smoking habit (P = 0.85) and serum cholesterol (P = 0.89). Senior staff had significantly higher values in age distribution (P < 0.001), presence of systolic hypertension (P<0.001) and overweight (P < 0.001). Senior staff workers, were however, significantly less involved in moderate exercise than junior staff (P < 0.001). The senior staff had a significantly higher total score in CVD risk scoring than junior staff (chi2 = 7.25; P = 0.01). In conclusion, the risk of CVD among staff of FUTO is high especially among the senior staff. Health education campaign targeted at improving life style is strongly recommended. PMID- 17722418 TI - Seasonal variation in human African trypanosomiasis in Tarangire National Park in Babati district, Tanzania. AB - A survey was carried out to determine seasonal epidemiological variation of human African trypanosomiasis (HAT) in Tarangire National Park and villages around it in Babati District, Tanzania. Concentration and Field's stain techniques were employed to examine the presence of trypanosomes in human blood samples. Tsetse flies were collected using traps and dissected under light microscope to examine for presence of trypanosomes. Retrospective data on HAT were sought from health facilities. Blood samples were collected from a total 509 individuals (306 during the dry and 203 during wet seasons). None of the individuals was infected with trypanosomes in the area. A total of 766 tsetse flies were collected. Of these, Glossina swynnertoni accounted for 94.6% and G. pallidipes for 5.4% of the total collection. The largest proportion (63.8%) of the tsetse flies was collected during the wet season. Glossina swynnertoni was most abundant tsetse species during both wet and dry seasons. Salivary gland examination revealed the presence of Trypanosoma brucei type of infection in 3.2% of tsetse flies collected. All infective trypanosomes were found during the dry season. This study concludes that the transmission and prevalence of HAT among human population in Tarangire National Pars and its surrounding villages is low despite the recent reports on tourists acquiring the infection during their visits to the Park. However, disease surveillance needs to be strengthened to monitor any impending epidemic. PMID- 17722419 TI - From research to policy: the role of health research institution in social development in Africa. PMID- 17722420 TI - The use of biochemical markers of bone turnover in osteoporosis. AB - OBJECTIVE: Present evidence-based recommendations on the use of biochemical markers of bone turnover in the management of osteoporosis. METHODS: The English literature from 1999 to 2005 was reviewed by using data sources from MEDLINE. RESULTS: Measurement of biochemical markers of bone turnover helps us identify a high bone turnover rate. Elevated levels of these markers points towards a pathology and at an accelerated loss of bone mass. Its main utility is in documenting the response to therapy. They have a limited role in the follow-up of patients with osteoporosis. To be useful, bone markers must be measured at baseline and periodically after the beginning of therapy. A fall of on fifty (50%) percent in the levels of resorption markers between the third and sixth month of therapy predicts a good response. Bone markers can not be used to establish the diagnosis of osteoporosis. Neither do they measure bone mass. Markers are not capable of predicting future loss of bone mass in an individual nor do they correlate with the occurrence of previous fractures. The greatest limitation of these measurements is not being able to measure bone remodeling in the individual subject. Bone resorption markers are more frequently used than those of formation. The levels of the markers can identify the failures to the therapy and responses to therapy. Lack of reduction in the resorption markers could indicate lack of compliance with therapy, problems of absorption of the medication or lack in response to treatment. There may be problems with the measurement and the interpretation of results of bone remodeling markers. Variability between individuals and intra-individual variability exist as well as inter-assay and intra-assay variability. CONCLUSION: Biochemical markers of bone turnover along with measurements of bone density can help optimize the management of osteoporosis. The use of the bone markers is not recommended in a routine form, but they can be of utility in situations of poor compliance with the therapy or when there are difficulties in the management of the treatment of osteoporosis. PMID- 17722421 TI - Major histocompatibility complex class II polymorphisms and risk of cervical cancer in Puerto Rican women. AB - Association between HLA antigens and cervical squamous cell carcinoma has been described in several populations. To verify whether HLA-DRB1 and DQB1 diversity is related to cervical cancer in Puerto Rican women, 40 cases and 50 controls were HLA typed. DRB1*16 (POR=2.89) and DRB1*11 (POR=1.74) were positively associated with cervical cancer. A negative association was found with DRB1*01 (POR=0.52), DRB1*04 (POR=0.60), DRB1*14 (POR=0.33), DRB1*15 (POR=0.65), DQB1*04 (POR=0.33), DQB1*05 (POR=0.64) and DQB1*06 (POR=0.65). We suggest that HLA Class H polymorphisms are involved in genetic susceptibility to cervical cancer in Puerto Rican women. These results should be confirmed in studies with larger sample size to preclude the possibility of false positive observations. PMID- 17722422 TI - Hepatocellular carcinoma: ten years experience among veterans in Puerto Rico. AB - PURPOSE: The aim of our study is to determine the characteristics of hepatocellular carcinoma (HCC) as well as risk factors, demographics, survival rates and the use of diagnostic and therapeutic modalities among veteran patients in Puerto Rico. METHODS: A retrospective study of 114 patients with Hispanic background and biopsy-proven HCC diagnosed at the VA Caribbean Healthcare System from 1992 to 2002 was performed. Demographics data, Child-Turcotte-Pugh (CTP) score, presence of cirrhosis, viral serology, alcohol and/or other liver diseases history, diagnostic modalities, lesion size, therapy, and overall survival were examined. RESULTS: The mean age was 66.6 years old. 82% had known underlying cirrhosis. 60% had alcoholic liver disease (ALD), 33% positive serology for hepatitis C (HCV) and 21% both. 5.3% had chronic hepatitis B virus (HBV) infection. Additional causes were not present. CTP classification was: A (42%), B (44%) and C (14%). Abdominal CT scan demonstrated most of the lesions, while ultrasound only 57%. Alfa-fetoprotein was diagnostic in 32%. Mean survival was 10.3 months, better for those with CTP score A. Only 42% of the patients received any kind of therapy. CONCLUSIONS: ALD is the principal underlying liver disease in our HCC patients, closely followed by chronic HCV infection. Less than half of our patients received treatment mainly due to advanced disease for which the over survival was less than a year. HCC continues to be a dreadful disease with poor prognosis for which aggressive screening should be considered for all patients with cirrhosis and advanced liver disease regardless of the cause. PMID- 17722423 TI - Risk factors for atopic dermatitis in southern Puerto Rico. AB - BACKGROUND: Little is known about the risk factors and exposures to aeroallergens in subjects with atopic dermatitis (AD) in Southern Puerto Rico. The objective was to determine the prevalence of skin reactions to aeroallergens and to analyze self-reported risk factors in AD patients and a nonallergic control population. METHODS: A cross-sectional study was conducted which included 726 AD patients and 313 nonallergic control subjects. Skin tests were conducted and a questionnaire was self-applied to all participants. RESULTS: Seventy six percent of the AD patients showed at least one positive skin reactions to aeroallergens. Of these, half had positive skin reactions to dust mites, and one third to Periplaneta americana. A low prevalence of positive skin reactions to dog, cat, plant and fungal allergens was detected. Co-sensitivitity between mites and cockroaches was 30%. The maximum skin reactivity to mites was at 10-19 years of age declining thereafter while skin reactivity to dogs, and plants increased with age. No significant differences in the prevalence of skin reactions was observed between the male and female AD population. CONCLUSIONS. Of the aeroallergens tested, those derived from dust mites are the most frequent sensitizing agents in the AD patients. Data also showed that the mites B. tropicalis and E. maynei are also important sources of sensitization. Our study show that young patients specially those between the age of 10-19 age group are the most allergic. Being female, or having an asthmatic father are significant risk factors associated with allergen sensitivity in the AD population. PMID- 17722424 TI - Correlates of early sexual activity among Hispanic children in middle adolescence. AB - OBJECTIVE: We analyzed early sexual activity among Hispanic 14 to 15-year-old adolescents residing in a poor neighborhood in Puerto Rico. METHODS: Information from a sample of 325 adolescents was collected from a randomized sample of community households. Logistic regression analysis was used to identify the variables that help explained adolescents' sexual behavior. RESULTS: Adolescents whose parents reported poor communication and poor parent control were more likely to engage in early sexual activity that those peers that did not report this type of family relationship. Adolescents who reported poor parent bonding and lack of discipline were more likely to engage in early sexual relationships. CONCLUSIONS: Intervention and prevention programs need to be aware and address the role of the Hispanic culture in gender differences in early sexual activity in adolescence. If sexual norms related to gender role are changing in Puerto Rico, is a question that needs to be answered in future research. PMID- 17722425 TI - The prevalence of atopic dermatitis in Puerto Rican school children. AB - BACKGROUND: Atopic dermatitis is a common inflammatory disease of the skin that usually begins in childhood and its diagnosis depends on clinical criteria. Recent reports have indicated that the worldwide prevalence of atopic dermatitis is increasing. The objective of this study was to determine the prevalence of atopic dermatitis in schoolchildren between the ages of six and seven in two school districts in Puerto Rico. METHODS: The Laughter questionnaire, developed to determine the prevalence of atopic dermatitis in schoolchildren was translated and validated in Spanish. A population-based prevalence survey was conducted among second grade students in the districts of Guaynabo and Humacao, Puerto Rico. The prevalence of atopic dermatitis was determined by sex, school type (private or public), and geographical location (urban or rural) using the questionnaire. RESULTS: Ninety-two percent (92 %) of the eligible schools participated in the study. A total of 2,393 questionnaires were distributed with a response rate of 53 %. The prevalence of atopic dermatitis among the population surveyed was 24.8%. The prevalence of atopic dermatitis by sex or geographic location was not significantly different (p>0.05). An excess of atopic dermatitis was observed in private schools (31.0%) when compared to public schools (19.9%). The effect remained after controlling potential confounders (POR Mantel-Haenszel = 1.37; 95%CI: 1.07 - 1.42). CONCLUSION: This study presents evidence of a significant public health problem in Puerto Rico. The prevalence of atopic dermatitis in Puerto Rico is high and possibly a large percentage (70%) of the patients is not been diagnosed. PMID- 17722426 TI - Adaptation of the Medical Research Council Dyspnea Scale and the Oxygen Cost Diagram for its use in Puerto Rico. AB - INTRODUCTION: Dyspnea is a common and disabling symptom for patients with chronic lung diseases. The Medical Research Council Dyspnea Scale (MRC) and the Oxygen Cost Diagram (OCD) are widely used instruments validated in English to measure breathlessness. OBJECTIVE: To translate and culturally adapt the MRC and the OCD for its use in Puerto Rico. METHOD: The scales were translated to Spanish and back translated. They were tested in patients attending a pulmonary clinic to assess its relevance and comprehension. Subjects answered the instruments, had a structured clinical interview and provided feedback. A multidisciplinary committee analyzed the source of misunderstanding using the input of the subjects, the clinical physicians, and the evaluators; made adjustments, and retested the instruments until inconsistencies were not observed. RESULTS: Placing emphasis on time spent walking instead of distance traveled improved the discrimination between grade two and three in the MRC. In the OCD, placing the activities to the right side eased the interpretation of the scale. Numerical symbols were eliminated to minimize discomfort in the severely impaired subjects reluctant to mark the line near zero. Reversing the order of both scales encouraged a thorough reading of the activities from minimal to high energy demanding eliciting a more fitting response compared to structured clinical interview especially in the severely ill patient. CONCLUSION: Using cross cultural research methodologies to translate the MRC and OCD allowed the identification of differences in conceptualization when assessing the severity of dyspnea in Puerto Rico. Further testing is needed to confirm psychometric properties. PMID- 17722427 TI - Physicians and nurses: knowledge of clinical management of sexual aggression in children based on the sexual aggression survivors manual in Puerto Rico. AB - OBJECTIVE: To evaluate the knowledge of health professionals about clinical the management of sexual aggression in children based on the sexual aggression survivors manual in Puerto Rico. METHOD: The study population was composed of 150 health professionals (physicians and nurses). For the collected data, a self administered questionnaire was used. The response rate was 88.7% (n=133). Descriptive statistics, crosstabs tables and Chi-Square were used for the data analysis. RESULTS: 75.9% of the participants were unaware of physical indicators related to sexual aggression in children. Nevertheless, 66.2% of the participants recognized emotional indicators of sexual aggression. 82.7% of the participants think sexual aggression victims should be referred to the physician and nurse, followed by 20.4% that indicated the social worker. 94.7% of the participants were unaware of the correct steps to carry out in a crisis intervention with sexual aggression victims and 91.7% recognized that all information topics should be offered during the intervention. CONCLUSION: The results of this study confirm the necessity of intervention strategies to increase the knowledge of the participants about the correct clinical management of sexual aggression survivors. PMID- 17722428 TI - Prevalence of hemochromatosis in the Puerto Rico veteran population. AB - BACKGROUND: Hereditary hemochromatosis (HH) is a disorder of iron storage that results in iron overload. It's prevalence in Puerto Rico (PR) is unknown and the condition frequently undiagnosed. PURPOSE: Determine the prevalence of HH in the PR Veteran population. METHODS: Patients attending the San Juan VA Medical Center Laboratory for routine tests were invited to participate. Basic demographic data, symptoms related questionnaire, fasting samples for unbound iron binding capacity (UIBC) and serum iron were obtained. Transferrin saturation (TS) > or =45% was considered as iron overload. Patients with elevated TS had a second test done to confirm iron overload. Genetic testing was performed to patients with sustained elevated TS. RESULTS: Data from 521 of the 559 recruited patients was available for analysis. 59 patients had TS > or =45%. Iron overload was confirmed in eleven patients. Two patients were lost to follow up; one had secondary causes for iron overload. Eight patients underwent genetic testing. Genetic mutations associated with hemochromatosis were found in four patients. CONCLUSION: The estimated prevalence of confirmed iron overload in our population is 2%, similar to one in the United States, while the prevalence of genetic mutations associated to hemochromatosis is 0.76%, which is slightly higher. Both genetic mutations (C282Y, H63D) are equally seen in the evaluated population which is different from reports elsewhere. Physician awareness of the prevalence of HH in PR may result in increased screening and early identification of the condition. PMID- 17722429 TI - Disease evolution of patients with mycosis fungoides--a report of 30 cases. AB - Mycosis fungoides is the most common disease of the primary cutaneous T-cell lymphoma group. This is a retrospective study to evaluate the outcome of 30 patients with mycosis fungoides who were followed up for at least 3 years, 18 of them followed for 5 years and 9 of them followed for 7 years. A total of 10 patients achieved a sustained remission, 2 patients achieved a remission but then relapsed and three patients died from lymphoma-related death. It is concluded that the majority of the patients with T1 or T2 stage MF usually have a good prognosis. As a rule, those who do progress further in the disease have advanced stages at the moment of the diagnosis; the disease progression occurring during the first 3-5 years after diagnosis. PMID- 17722430 TI - Reflections on knowledge and wisdom in neurosurgery. PMID- 17722431 TI - Hepatopulmonary syndrome. AB - This is a report of a 56-year-old male who was admitted to the Intensive Care Unit of the San Juan V.A. Medical Center with altered mental status and severe hypoxemia. He was diagnosed with severe hyponatremia and hepatopulmonary syndrome. PMID- 17722432 TI - Assessment criteria for compliance with oral hygiene: application of ROC analysis. AB - PURPOSE: Diabetes is an established risk factor for periodontal disease. Management of periodontal disease is highly dependent upon effective oral hygiene. Assessment of plaque and gingivitis has been commonly used and arbitrarily set in clinical practice to evaluate patients' adherence with oral hygiene recommendations. This study aims to determine an objective cut-off criterion for assessing oral hygiene compliance utilising a combination of plaque and bleeding scores. MATERIALS AND METHODS: 161 patients with diabetes, from a prospective clinical trial, provided the clinical periodontal parameters at baseline to be used to determine the oral hygiene compliance criterion in relation to a composite score of pocket depth, subgingival calculus and supragingival calculus. A sequence of different combinations of plaque and gingival bleeding scores were used. Receiver operator characteristic (ROC) curve assessment, sensitivity, specificity, and predictive values were utilised for the determination of the criterion. RESULTS: The combination of 25% plaque scores and 15% gingival bleeding scores obtained the highest ROC value (using a probability cut-off of 0.5) of 0.868 with sensitivity 98.6%, specificity 75.0%, positive predictive value (PPV) 97.3% and negative predictive value (NPV) 85.7%. According to this criterion, amongst the cohort of subjects examined, 145 (90.1%) were categorised as non-compliant, and only 16 (9.9%) were considered compliant with oral hygiene at baseline. CONCLUSIONS: Based upon the clinical periodontal parameters of subjects from this study, a combination of 25% plaque score and 15% bleeding score appears to be a valid target for determining compliance with oral hygiene in oral health programmes. PMID- 17722433 TI - Effect of tongue cleansing on morning oral malodour in periodontally healthy individuals. AB - PURPOSE: The aim of this randomised single-blind, cross-over trial was to assess the effect of tongue cleansing on morning oral malodour in periodontally healthy subjects. MATERIALS AND METHODS: Ten systemically healthy non-smoker subjects (6 males, 4 females), 24-38 years of age, completed two 4-day periods of oral hygiene cessation with a 7-day wash-out period. In one of these test periods, subjects were instructed to clean their tongues with a tongue scraper 2-3 times a day. Participants presented at least 20 teeth, without cavities, overhanging restorations/prostheses or periodontitis, and had no history of previous periodontal therapy or use of antibiotics in the 3 months prior to the study. Volatile sulphur compounds (VSC; Interscan Halimeter) and organoleptic scores were measured in exhaled mouth air once a day, early in the morning, by one examiner. Comparisons were performed using Wilcoxon's signed rank test and Friedman's test (alpha = 0.05). RESULTS: VSC levels at baseline were 206.3 ppb (SD 139.8) and 191.4 ppb (SD 127.7) for periods of usage and non-usage of the scraper respectively (p > 0.05). VSC levels did not change significantly during the 4 days, independent of tongue cleansing (Friedman, p > 0.05). Only at day 3 did the use of the tongue scraper lead to a significantly lower level of VSC compared with controls (131.1 ppb and 199.3 ppb respectively). No significant differences in organoleptic scores were observed between groups at baseline. During the whole experimental period, there were also no significant changes in organoleptic scores when individuals used or did not use the tongue scraper. CONCLUSION: Tongue cleansing with a scraper was unable to prevent morning oral malodour in the absence of tooth cleaning in periodontally healthy individuals. PMID- 17722434 TI - An assessment of oral self-care among Romanian dental students using the Hiroshima University--Dental Behavioural Inventory. AB - OBJECTIVE: To determine the differences in oral self-care levels between 322 Romanian dental students. MATERIALS AND METHODS: The design of the study was a cross-sectional survey of dental students in Romania. The examination was based upon responses to a questionnaire entitled 'Hiroshima University--Dental Behavioural Inventory' (HU-DBI) and three additional questions. RESULTS: Statistically significant differences of the mean HU-DBI scores were observed between year 1 and 2 (level of basic science course) and year 5 and 6 (level of clinical course) and between genders (p < 0.001). Statistically significant differences were notable in 10 items out of 20 between three levels of dental education (basic, preclinical and clinical levels). The most striking results were that year 5 and 6 students were less likely to use a toothbrush with hard bristles (p < 0.001), and less likely to worry about the colour of their teeth (p < 0.01). While 20% of year 1 and 2 students reported daily flossing, almost 46% was reported in year 5 and 6 students (p < 0.001). A significant difference was also observed on flossing behaviour between genders (p < 0.001). Of 205 year 1-4 students, 176 (85.9%) were correctly predicted by the models, and 177 of 193 female students (91.7%) were correctly predicted. CONCLUSIONS: There were considerable differences in dental health attitudes/behaviour between the three levels of dental education and between genders. PMID- 17722435 TI - Health control beliefs and quality of life considerations before and during periodontal treatment. AB - PURPOSE: Previous studies have indicated that health beliefs are related to the periodontal disease status and treatment behaviour of patients. However, it is possible that treatment may affect a patient's health beliefs and thus complicate this issue. The present study therefore looked for changes in health control beliefs and oral health impacts in patients undergoing periodontal treatment in a dental school. MATERIALS AND METHODS: Questionnaires assessing dental multidimensional locus of control (LOC) and oral health impact profile (OHIP) were posted to subjects due to attend for initial periodontal consultation and were returned by 127 patients who attended. Repeat questionnaires were sent to all subjects 6 months later when they had received some oral hygiene instruction, scaling and root planing, and 55 were returned. RESULTS: Comparison of data for those subjects who completed both questionnaires showed no difference in LOC but showed a trend (p = 0.065) towards reduced OHIP (i.e. improved oral health related quality of life). CONCLUSIONS: These subjects apparently did not alter their health control beliefs about periodontal disease as a result of treatment, but there may have been an improvement in their oral health-related quality of life. Further studies are required to confirm these possibilities. PMID- 17722436 TI - Periodontal conditions in a Swedish city population of adolescents: a comparison between smokers and never-smokers. AB - PURPOSE: The aim of this study was to evaluate the influence of smoking on the periodontal conditions of a randomly selected population sample of 19-year-old individuals. MATERIAL AND METHODS: A population sample of 272 randomly selected 19-year-old individuals living in Goteborg, Sweden, was clinically examined with regard to oral hygiene, gingivitis, deepened periodontal pockets, probing attachment loss (PAL) and gingival recession. On bitewing radiographs, alveolar bone level and presence of dental calculus were assessed. The subjects were classified as 'never-smokers' or smokers based on information obtained by a questionnaire-based interview. RESULTS: The mean plaque and gingivitis scores were for never-smokers 58% (SE 1.7) and 46% (1.4) respectively, and for smokers 60% (2.2) and 42% (2.1) respectively. Of the never-smokers and smokers respectively, 38% and 35% showed a prevalence of gingivitis of > 50%. The mean number of sites with periodontal pockets > or = 4 mm was 12 (0.9) in never smokers and 13 (1.4) in smokers. Of both never-smokers and smokers, 75% did not have any site with PAL > or = 2 mm, and only six individuals (3%), all never smokers, showed more than three sites with a PAL of > or = 2 mm (facial sites). Logistic regression analyses revealed that smoking was a poor discriminator for identification of subjects with periodontal destruction (OR 0.62-1.33). CONCLUSIONS: In the present population sample of adolescents, characterised by high prevalence of plaque and gingivitis, smoking habits did not contribute to a higher prevalence or severity of periodontal destruction. PMID- 17722437 TI - Marginal bone loss over 5 years in an adult Danish population. AB - PURPOSE: To evaluate marginal bone loss on the individual and tooth level, with focus on the importance of the baseline marginal bone level. MATERIALS AND METHODS: In 1997, 616 randomly selected individuals (mean age 42 years, range 21 63 years) underwent a full-mouth radiographic survey. In 2003, the survey was repeated for 473 of the same individuals (239 females and 234 males). The marginal bone level of each tooth was measured in mm from the cemento-enamel junction to the marginal bone. These measurements were used to calculate marginal bone loss during the 5-year period, and to analyse the average marginal bone loss for the individual, and tooth group in relation to age and to baseline marginal bone level, calculated as the average between measurements in 1997 and 2003 to circumvent regression to the mean. RESULTS: Marginal bone loss rate was on average 0.1 mm per year. For the individual, marginal bone loss was associated with both baseline marginal bone level and age. A significant difference was shown (p < 0.05) in marginal bone loss between different age groups, with a stronger association between marginal bone loss and baseline marginal bone level in the youngest age group. Moreover, marginal bone loss differed between tooth groups (p < 0.001), with molars and premolars losing marginal bone more rapidly than incisors and canines and showing a stronger association with baseline marginal bone level. CONCLUSIONS: Marginal bone loss over a 5-year period is associated with age and baseline marginal bone level. Younger individuals with a reduced marginal bone level were at high risk for further bone loss. Molars and premolars exhibit more rapid marginal bone loss than incisors and canines. PMID- 17722438 TI - Use of the limits of agreement approach in periodontology. AB - PURPOSE: To discuss the statistical approaches that have been traditionally used to compare measures in periodontal research, highlighting its strengths and weaknesses and, finally, to suggest the use of the limits of agreement method of Altman and Bland (1983) as an alternative method to address this question. MATERIALS AND METHODS: Using a sample dataset of clinical periodontal measures as a background, the different possible approaches for agreement assessment are discussed and statistical and clinical points are considered. Eight hundred and forty repeated measures, belonging to the training phase of a clinical study, were performed in five individuals presenting different severities of periodontal conditions. The use of correlation coefficient, comparison of means, linear regression technique, Kappa coefficient, intra-class correlation coefficient and means versus differences plot is demonstrated. RESULTS: Most of the methods are applied without the appropriate care, resulting in misleading interpretations. The information that arises from some of the methods used so far is poorly informative and adds little understanding to the operational characteristics of the raters or instruments. Some of the resulting information from the correlation coefficient and kappa coefficient may even be false or not applicable for the entire range of possible values. CONCLUSIONS: The graphical approach that plots differences against means, including the 95% limits of agreement estimated by the mean difference +/- 1.96 standard deviation of the differences is the most informative approach and its application should be considered for continuous clinical periodontal measures. PMID- 17722439 TI - Tooth loss is related to the presence of metabolic syndrome and inflammation in elderly subjects: a prospective study of the vasculature in Uppsala seniors (PIVUS). AB - PURPOSE: To investigate how the number of remaining teeth relates to the presence of metabolic syndrome (MetS) and markers of inflammation. MATERIALS AND METHODS: A population-based prospective investigation of the vasculature in Uppsala seniors (PIVUS) study was carried out on 1016 subjects, aged 70. RESULTS: The number of teeth was self-reported in 947 subjects and was found to be less in those with MetS using National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP Ill) criteria (n = 219, mean 17.7 +/- 9.0 [SD]), compared with n = 728, mean 20.7 +/- 7.2 in those without MetS (p < 0.0001), and in proportion to the number of criteria fulfilled (p < 0.0001). The number of teeth was also inversely related to markers of inflammation (r = -0.15, p < 0.0001 for leukocyte count; r = -0.10, p = 0.0023 for C-reactive protein). In a multiple regression analysis, the presence of MetS, smoking, educational level, leukocyte count and height were independent predictors of the number of teeth. CONCLUSIONS: In addition to established risk factors for tooth loss, the presence of MetS and inflammation were independent predictors of the number of teeth in an elderly population. PMID- 17722440 TI - Thresholds of restorative decision in dental caries treatment among dentists from small Brazilian cities. AB - PURPOSE: To investigate the thresholds of restorative intervention in dental caries treatment, based upon the lesion depth seen in radiographs, among Brazilian dentists working in small cities. In addition, the threshold of restorative intervention was compared with demographic and work-related characteristics. MATERIAL AND METHODS: The studied population comprised dentists (n = 89) who were working in 2000 in 20 small cities of the Midwest region of the Southern Brazilian State of Santa Catarina. Four different radiographs were shown of extracted premolars fixed upon a plaster base. The criteria for the radiograph analyses were proposed by Nuttall et al (1993). RESULTS: Of investigated dentists, 16.7% would restore a carious lesion confined to the outer half of the enamel and 33.3% would restore a carious lesion in the outer and inner half of the enamel, but without involving the enamel-dentine junction. The percentage that would restore lesions in the outer half of dentine was 91.7%. Dentists who had attended postgraduate courses in areas of interest of this study tended to adopt a more conservative treatment when compared with dentists who had not attended (p < 0.01). CONCLUSIONS: There was a great variation in the thresholds of intervention based upon lesion depth seen in radiographic images amongthe investigated Brazilian dentists. An interventionist attitude was observed, which could result in over-treatment. It is highly recommended to educate general practitioners from the studied region in performing early diagnosis of lesions and non-invasive care in order to treat initial carious lesions with only remineralisation and monitoring. PMID- 17722441 TI - Comparison of epidemiological evaluations under different caries diagnostic thresholds. AB - OBJECTIVE: To investigate the influence of different settings, epidemiological and clinical, and different diagnostic thresholds on caries detection in a group of 7-10-year-old children in Brazil. MATERIALS AND METHODS: In total, 983 children aged 7-10 years old and enrolled in four public schools were randomly selected. Three examiners performed epidemiological examinations followed by an examination of the same children in a clinical setting. The examinations of cleaned and dried teeth in both settings were carried out using a dental mirror and ball-ended probe, under natural light in the epidemiological setting examinations and under artificial light during the clinical setting examinations. For the analysis of results, comparisons were focused on WHO (World Health Organization) diagnostic thresholds versus WHO+IL (initial lesions) diagnostic thresholds, both under epidemiological conditions, in order to demonstrate the influence of the inclusion of IL in the study; and WHO+IL in the epidemiological setting versus WHO+IL in the clinical setting, aiming to demonstrate the importance of examination setting. Outcome measures were dmfs, DMFS, ds, Ds, sealants and number of children 'free' of caries. Paired t-test and McNemar's test were used to test the difference between means and proportions for each age group. RESULTS: Epidemiological examinations, under the WHO diagnostic threshold, showed significant differences for all outcome measures when compared with the WHO +IL threshold. Statistical differences were also detected when comparingthe WHO+IL threshold under different settings. CONCLUSION: The choice of a diagnostic threshold (WHO or WHO+IL) and the conditions of examination (epidemiological or clinical) were important for caries detection. PMID- 17722442 TI - Fluoride interventions for root caries: a review. AB - PURPOSE: To review in a systematic approach the effectiveness of specific fluoride treatments on the root caries activity in adults. MATERIALS AND METHODS: An electronic search of the National Library of Medicine, Washington DC (Medline PubMed), and the specialist trials register of the Cochrane Oral Health Group up to and including April 2005 was performed using specific search terms to identify randomised controlled trials, controlled clinical trials and longitudinal studies of at least 3 months duration, which investigated the effect of specific fluoride treatments with regard to root caries activity and/or incidence in healthy adults. Comparisons were made against the root caries status before the initiation of the additional fluoride application regimen and between groups in controlled studies. The papers were screened independently by two reviewers (MH and SP). RESULTS: Out of 348 titles and abstracts, six papers fulfilled the selection criteria and were processed for data extraction. The highest level of evidence was presented in the two papers using a double-blind controlled randomised clinical trial (Wallace et al, 1993; Baysan et al, 2001). Both these studies indicate that the increased application of fluoride in the form of a high concentration dentifrice or additional mouthwash had a positive effect on the root caries incidence/severity. CONCLUSION: Additional fluoride appears to be a preventive and therapeutic treatment for root caries. PMID- 17722443 TI - Odontogenic infection sources in patients scheduled for cardiac valve replacement. AB - PURPOSE: Odontogenic infection sources represent a predisposing risk factor for patients with cardiac valvular disease (CVD) awaiting cardiac valve replacement procedures. STUDY DESIGN: The incidence and quality of odontogenic infection sources (foci) were evaluated on 152 consecutive patients (study group, SG) undergoing cardiac valve replacement and were compared to 150 age-, gender- and residence-matched non-cardiac patients (control group, CG). Clinical and radiographic examinations were used to evaluate the incidence of odontogenic infection sources, grouped into potential (high risk) and facultative foci (possible risk), and the presence/severity of periodontal disease (PD). Foci and PD were compared among the overall SG and the CG and also among a sophisticated subdivision of the study group, especially with respect to aortic valve (AVR) and mitral valve replacement (MVR). RESULTS: Overall, 218 potential and 116 facultative odontogenic foci were found in 87 (58.3%) and in 79 (51.9%) patients of the SG respectively. The overall incidence of odontogenic infection sources and the incidence and severity of PD did not differ between the SG and the CG. However, in comparison with the CG (48%), the incidence of potential odontogenic infection foci was significantly higher in patients scheduled for AVR than in those scheduled to undergo MVR (70.4% vs. 25.0%, p < 0.01). Additionally, in patients scheduled for AVR, a significantly higher number (p < 0.01) of individual potential dentogenic infection foci (1.7 vs. 0.8 foci/valve) and a higher prevalence of PD (60.2%) was seen than for patients scheduled for MVR (31.8%) or for patients without CVD (1.0 foci/valve; 39.3%; p < 0.05). DISCUSSION: Although the overall incidence of odontogenic infection sources did not differ between the patients with and without CVD, a sophisticated subdivison of CVD may be crucial, demonstrating that patients with AVR differ significantly from those with MVR and with the healthy CG. Cardiologists and cardiac surgeons play an important role in organising oral rehabilitation of patients scheduled for valve replacement. PMID- 17722444 TI - [In vitro phenotypic characterization of human limbal epithelial cells]. AB - INTRODUCTION: Human limbal epithelial cells (huLEC) have been used for clinical purposes in ocular surface diseases to promote rapid re-epithelisation and restore corneal epithelium integrity. However, in Mexico this technique has not been fully developed. This study was conducted to characterize the huLEC phenotype expanded in vitro using a cell culture technique. MATERIAL AND METHODS: Cells were obtained from limbal tissue, cultured in KSFM medium and analyzed for the expression of vimentin, K, K19, p63, K12, by flow cytometry and immuno fluorescence. RESULTS: The phenotype of cultured cells was vimentin+K+K19+ p63+K12-. CONCLUSIONS: Our results suggest that under these culture conditions huLEC maintained their stem cell phenotype. This culture technique could be used for clinical purposes in Mexico. PMID- 17722445 TI - [Comparative clinical study of dexamethasone vs. nebulized salbutamol in acute bronchiolitis]. AB - OBJECTIVE: Asess the efficacy of nebulized salbutamol and dexamethasone compared with nebulized salbutamol, in patients with bronchiolitis. MATERIAL AND METHODS: A blinded clinical trial was performed with 49 patients between 1-18 months diagnosed with bronchiolitis with three days or less of disease evolution. Participant's parents signed an informed consent and patients did not receive prior medication. Patients were randomly assigned to two groups: nebulized salbutamol or salbutamol plus dexamethasone, which they received every four hours during twenty-four hours. We measured heart and respiratory rate; respiratory distress index, oxygen saturation, and Silverman Andersen scores. RESULTS: No significant differences were found between groups for treatment response; but the frequency of hospital release at 24 hrs was significant among groups; 75 vs 96 % respectively (p = 0.04). CONCLUSIONS: The administration of salbutamol plus dexamethasone is more effective in the control of respiratory distress in children with bronchiolitis compared with the use of salbutamol alone. PMID- 17722446 TI - [Asymptomatic fungemia caused by Acremonium sp associated with colonization of a central venous catheter]. AB - BACKGROUND: Microorganisms considered saprophytes have emerged as invasive or indolent pathogens among immuno-compromised patients. MATERIAL AND METHODS: We detected an initial case of catheter-related Acremonium sp fungemia on a previously asymptomatic patient. We diagnosed a second case five weeks later. Both patients had a non-tunneled central venous catheter (CVC) that had been cared for following routine protocol by nurses in the Intravenous Therapy Team on a weekly basis. The sole risk factor that both patients shared was that they had received total parenteral nutrition (TPN) by a CVC 5 months prior to the date the catheter-related fungemia was detected. We retrospectively studied all patients who had received TPN during this period. RESULTS: We found two cases ofAcremonium fungemia, patients had gastric adenocarcinoma and received TPN for an average of 19 days. Infection was resolved with catheter removal and antifungic therapy. Another eight patients received TPN from the same commercial firm during this period; average administration was 9.5 days (range, 6-20). Neither blood cultures nor tip-catheters culture reported Acremonium sp. CONCLUSIONS: Patients with CVC for TPN should be closely monitored to identify colonization with a low pathogenic microorganism that could be mistakenly diagnosed as asymptomatic. PMID- 17722447 TI - [Increased mortality and disability in a cohort of Mexican children with maple syrup urine disease]. AB - INTRODUCTION: Maple syrup urine disease (MSUD) is a genetic disorder that produces ketoacidosis crises and neurological complications often leading to death. The age of diagnosis and treatment determine a child's adequate and healthy outcome. OBJECTIVE: Describe the characteristics of a pediatric Mexican cohort with MSUD. MATERIAL AND METHODS: Retrospective analysis of MSUD cases seen at our Metabolic Unit between 1991- 2006. RESULTS: We studied 36 patients; three were initially detected through neonatal screening, one of them done in Mexico and two in the United States. The latter were given timely treatment and developed normally, both intellectually and physically. The patient detected in Mexico was not given adequate treatment and died at 3 months of age. The remaining 33 patients were diagnosed between 2-24 months using standard biochemical tests performed after symptoms became noticeable. All symptomatic patients had high levels of branched-chain amino acids. Hypotonia, refusal to eat and seizures were the most frequent symptoms. The cohort's mortality was 50% (18/36), while 81.2% (13/18) of survivors displayed cognitive impairment. DISCUSSION: Mexico needs a comprehensive treatment protocol for the care of MSUD patients including newborn screening, early treatment, follow-up and genetic counseling. PMID- 17722448 TI - [Management of chronic subdural hematoma with twist-drill craniostomy. Report of 213 patients]. AB - OBJECTIVES: Controversies regarding the surgical management of chronic subdural hematoma still remain. The objective of the present study was to describe our experience with twist-drill craniostomy. PATIENTS AND METHODS: Two hundred and thirteen patients were treated at the "Teodoro Maldonado Carbo" and "Alcivar" facilities between January 1992- February 2005. The surgical technique consisted of a twist-drill made under local anesthesia at the patient's bedside. We administered the Markwalder grading scale and the Glasgow outcome scale to assess treatment results. Clinical outcome, complications and relapse were measured. RESULTS: The etiology was traumatic in 65% of cases. At admission, 79% scored 2 of the Markwalder grading scale. Nine percent of the patients displayed complications. The chronic subdural hematoma persisted in 8%; they were treated again with another twist-drill craniostomy with favorable results. At six months, 97.6% reached 5 in the Glasgow outcome scale. CONCLUSIONS: Twist-drill craniostomy is a less time consuming, safe, effective, and cost-efficient method for the treatment of chronic subdural hematoma. PMID- 17722449 TI - [Lymphatic mapping and sentinel lymph node biopsy in patients with high risk squamous cell carcinoma of the skin]. AB - BACKGROUND: Some sub-groups of cutaneous squamous cell carcinoma (CSCC) display a higher risk for regional metastasis. Sentinel lymph node staging has been used successfully to evaluate nodal metastasis in selective tumors. OBJECTIVE: Assess the feasibility of sentinel node to detect occult regional lymph node metastasis in high-risk CSCC. MATERIAL AND METHODS: Between January 2002 and March 2004, a total of 20 patients received pre-operative lymphoscintigraphy and sentinel lymphadenectomy for high-risk CSCC with clinically non-palpable regional lymph nodes. RESULTS: In one of each 5 patients (20%), sentinel lymph node showed histological evidence of microinvolvement. No patients with negative sentinel node showed tumor dissemination during follow-up, with a mean of 23.5 months (range 7-44). CONCLUSIONS: Sentinel lymph node biopsy is technically feasible with low morbidity. Sentinel lymphadenectomy may play an important role in the management of high-risk CSCC with clinically non-palpable regional lymph nodes. This technique can help identify patients with regional lymph node metastases who may benefit from complete lymphadenectomy. This improved staging may allow clinicians to better stratify patients who might benefit from adjuvant therapy. PMID- 17722450 TI - [Research at the School of Medicine, UNAM. Historical review of the last 50 years]. PMID- 17722451 TI - [Eight years using the "Mexican method" for allogeneic hematopoietic stem cell transplants]. AB - In the past eight years, in Mexico and in other developing countries, over 350 patients have undergone allogeneic hematopoietic stem cell transplants using a non-myeloablative conditioning regimen developed in Mexico and based on international standards. The so called "Mexican method" to conduct allogeneic stem cell transplants is endowed with certain advantages which make it affordable and in turn, available to individuals living in resource-poor countries. The best results using this method have been observed among patients with stage 1 chronic myelogenous leukemia and aplastic anemia. The less favourable results have been observed among patients with acute lymphoblastic leukemia; mild to moderate results have been reported among patients with acute myelogenous leukemia. The "Mexican method" to conduct hematopoietic cells allografting has resulted not only in turning this method accessible to patients in developing countries, but also it has witnessed an increase in the academic activities of physicians from these countries involved in the field. PMID- 17722452 TI - [Historical development and current concepts on B-cell lymphomas of the marginal extraganglionar site of lymphoid tissue associated with MALT lymphoma. A tribute to Dennis H Wright and Peter G Isaacson]. AB - Significant advances in the understanding of marginal zone lymphoma since the first description in 1983 by Peter Isaacson and Dennis Wright have been noted. MALT lymphomas are a subgroup of low-grade B-cell lymphomas that arise from extranodal sites, comprising 7-8% of all B-cell lymphomas and displaying distinct clinicopathological characteristics. MALT lymphomas remain localized in the primary site for long periods of time and seldom disseminate unto other organs. These type of lymphomas infrequently arise in native MALT, but instead arise in MALT acquired in the course of chronic inflammatory disorders, such as Sjogren's syndrome and Helicobacter pylori infection. Eradication of H. pylori produces a clinical regression of the lymphoma in about 75% of cases. The histological hallmarks of MALT lymphoma include neoplastic centrocyte-like B cells, cells resembling monocytoid cells and the presence of lymphoepithelial lesions. The gastrointestinal tract, particularly the stomach, include two-thirds of cases; however MALT lymphomas also occur in other organs such as salivary glands, lung, thyroid, ocular adnexa, breast and skin. Genetic studies have identified three chromosomal translocations specifically associated with MALT lymphomas that include: t(1l:18)(q21;q21), t(1;14)(p22;q32), and t(14;18)(q32;q21). Although these translocations involve different genes, they appear to share a common oncogenic pathway involving NFkappaB. PMID- 17722453 TI - [A 24-year-old woman with cephalea and severe depression]. PMID- 17722454 TI - [Is it possible to cure a patient with mycosis fungoides? A case report]. AB - Sezary syndrome (SS) and mycosis fungoides (MF) are a group of non Hodgkin lymphomas that originate from T-lymphocytes and involve mostly the skin. These entities are generally non treatable and patient prognosis remains poor even with the advent of current treatment schedules. Complete remissions are seldom observed. For this reason, bone marrow transplant has been used as a treatment option. The high mortality associated with this procedure has turned reduced intensity conditioning stem cell transplant into a treatment option. This case study illustrates how stem cell transplant offers complete remission of this type of lymphomas. PMID- 17722455 TI - [Blindness due to head injury in an adolescent patient]. AB - We describe the case of a 15 year old male adolescent with blindness of the right eye secondary to frontal head injury and blindness as the sole complication. Computed tomography and magnetic resonance imaging studies were both normal. We postulate a non anatomical severing of the optic nerve as the etiological cause for blindness. Clinical management included intraocular steroids. The patient was discharged with unilateral blindness and followed-up in outpatient care. PMID- 17722457 TI - [First case report in Mexico of a diaphragmatic hernia, by Agustin Arellano in 1839]. AB - Reports on partial lacking of the diaphragm and diaphragmatic hernia date to seventeenth century reports. In 1939 Arellano published in Mexico, a necropsy case of diaphragmatic hernia with holoprosencephaly and cyclocephaly. Agustin Arellano's was the the fifth or sixth report ever published worldwide and his manuscript was reported nine years before Bochdalek's publication. Before 1839, in the Americas, there is no other existing report describing this type of pathology, and we can safely assume Arellano's work was the first of its kind in the Western hemisphere. It is well known that, at the time, the quality ofscientific publications of this Mexican medical researcher could be compared to the level of any medical publication in the developed world. It is worth noting that the Journal were Arellano's work was published, named "Periodico de la Academia de Medicina de Megico (sic), "founded and directed by Dr. Manuel Carpio in 1836, is the direct precursor of the present-day "Gaceta Medica de Mexico" the oldest current medical journal in the Americas. PMID- 17722456 TI - [A case report of a primary lung leiomiosarcoma]. PMID- 17722458 TI - [Stem cells and the origin of colon cancer]. PMID- 17722460 TI - [A clinician in the 21st century]. AB - At the beginning of the 21st century, clinical practice faces new challenges associated with very fast scientific and technological advances. Societies have also changed and current conditions demand modernization of clinical practice. Now we acknowledge the need for a patient-centered medical practice. Novel technologies will also participate in this new social fabric. This is the new clinical practice of the 21st century. PMID- 17722459 TI - [The status of the human embryo from a gradualistic perspective]. AB - Bioethics debates topics regarding the beginning and ending of human life. The beginning of human life includes when a human embryo reaches full human status. There are multiple and interesting issues surrounding human embryo status. These include assisted reproduction, seeking and management of human gametes and embryos at specialized laboratories, embryonic and stem cell research, emergency contraception, voluntary interruption of pregnancy, etc. They are based on implicit or explicit philosophical concepts. Philosophical positions about human embryo status could be summarized in two postures: personalism and gradualism. Personalism considers that human embryos reach the status of persons from the moment of fertilization. On the other hand, gradualism considers human embryos become persons at a later time after fertilization. The present work discusses the definitions of "status" and "embryo", summarizes criteria to consider a human being as a person, presents gradualism as an alternate posture to personalism, and finally emphasizes Alonso Bedate's gradualist position about human embryo status, suggesting that gradualism has its metaphysical foundation in modern biology. PMID- 17722461 TI - [Clinical evaluation of posterior occulusal support in removable partial dentures]. PMID- 17722462 TI - [Biological response to dental interventions]. PMID- 17722463 TI - [Development of a three-dimensional occlusal force sensor]. AB - The aim of this study was to develop a three-dimensional small occlusal force sensor which could be set up inside the crown of the tooth and measure both the three-dimensional occlusal force and the tooth displacement path during function at the same time in vivo. The measurement error of this occlusal force sensor was 11.9%, 8.7%, and 5.9% at maximum in the mesio-distal, bucco-lingual and colono apical directions, respectively. The subject was a Japanese male who had good periodontal conditions and an acceptable centric occlusion. After this occlusal force sensor and tooth displacement transducer were set up at the upper left first molar, the three-dimensional occlusal force and the tooth displacement were measured simultaneously during clenching at the intercuspal position and biting a ready-made monoaxial occlusal force meter. During clenching at the intercuspal position, the tooth displaced toward the palato-disto-apical direction and this was almost the same direction in which the occlusal force acted. The difference between the values measured by this sensor and a ready-made monoaxial occlusal force meter was about 9.5% at maximum. This three-dimensional occlusal force sensor is able to reveal how occlusal force is diffused. PMID- 17722464 TI - [Relationship between mechanical stimulation to the teeth and sternocleidomastoid muscle activities in human]. AB - Concomitant head and mandibular movements in mastication are thought to be regulated by sensory inputs to the stomatognathic receptors. In rats, a reflex pathway from the periodontal mechanoreceptors to the neck muscles has been reported. However, no such pathway has been found in humans. The aim of this study was to find whether pressure stimulation to the teeth influences neck muscles in humans. The subjects were 8 healthy adults who were asked to sit in a chair with a backrest and a headrest so that the head was fixed. The upper right canine was subject to pressure by an electrical-powered stimulator in a posterior anterior direction. The pressure was applied in a ramp-and-hold stimulation. Maximal continuous loading was 2 N with a ramp speed of 4 N/s and the stimulation interval was 5 s. The motor unit activities of the right sternocleidomastoid muscle (SCM) were recorded by needle electromyogram and analyzed as instantaneous frequency. As a result, instantaneous frequencies of activity of all 14 motor units significantly increased from 11.8 +/- 1.4 Hz before stimulation to 15.4 +/- 1.5 Hz during stimulation (p < 0.01). This result suggests that pressure stimulation to teeth induced the tonic discharge of the SCM. Therefore, there is a functional relationship between the teeth and neck muscles in humans. PMID- 17722465 TI - [Relationships between application for the School of Oral Health Care Sciences and awareness as a dental hygienist]. AB - The aim of this study was to investigate students' awareness of applying for the School of Oral Health Care Sciences, Tokyo Medical and Dental University and being dental hygienists in the future. Forty-seven students (24 first-year students and 23 second-year students) in the school answered the questionnaire including questions about becoming dental hygienists and certified social workers. We requested them to answer by recalling their thoughts at the time of application. The chi-square test and Fisher's exact test were used for statistical analysis. A significantly larger number of the first-year students thought that a dental hygienist was an attractive occupation compared with the second-year students. The time when first-year students decided to apply for the school was classified into three categories: by August, from September to December of the year preceding admission, and January or February of the admission year. The ratios of the students who decided to apply for the school were 42%, 21%, 38% respectively. The results of analyzing first-year students' questionnaire responses were as follows. A significantly larger number of students who wished or decided to apply for the school by August of the year preceding admission also applied for other dental hygiene programs. The number of students who thought that a dental hygienist was an attractive occupation was significantly greater among the students who wished or decided to apply for the school by August of the year preceding admission than among those who didn't. We consider that these students were highly motivated to become dental hygienists. It is important for the school to recruit students with high motivation. PMID- 17722466 TI - [Effect of the viscosity of alginate impression materials on the preliminary impression for complete dentures]. AB - The purpose of this study was to clarify the effect of the viscosity of alginate impression materials on the results of the preliminary impressions for complete dentures. Five experimental alginate impression materials with different viscosity were prepared based on a conventional material. Fifteen complete denture wearers were selected and impressions on using the experimental materials were taken. Impressions were evaluated by the success rates at the mylohyoid ridge area (MR), buccal area (BL) and retromolar pad area (RP). The success rates had a tendency to increase as the viscosity rose at MR and RP. The success rates at BL were not significantly different among the materials. Our results indicate that the viscosity of alginate impression materials has a great effect on the results of preliminary impression for complete dentures, especially at MR. Impression materials with high viscosity may be suitable for recording the anatomical form of the alveolar ridge better than those with low viscosity. PMID- 17722467 TI - [An effective biological marker to detect oral squamous cancer cells--expression patterns of CK 10, 17, 19 and SCCA mRNA--]. AB - A variety of techniques have been employed for the detection of tumor cells in the lymph nodes of patients with oral squamous cell carcinoma (OSCC). Molecular analysis has been applied to detect metastases and several reports have presented examinations of tumor markers, but no target gene that is completely reliable as a molecular biological tumor marker has been found. This study investigated whether a marker exists that is effective to detect OSCC. A total of 134 samples (biopsy and surgical specimens) from 102 OSCC patients were analyzed. Expression patterns of Cytokeratin (CK) 10, 17, 19 and SCCA mRNA in the normal oral mucosa and OSCC samples were examined using RT-PCR. Statistical analyses showed that significant differences existed in expressions of CK 10, 17, 19 and SCCA between OSCC and the normal mucosa (p<0.05). No correlation was observed between the degrees of histological differentiation of the tumor and CK 17 expression. The CK 17 expression also showed no significant differences depending on sites of primary tumors. Among the CK 10, 17, 19 and SCCA investigated, only CK 17 showed high sensitivity and negative predictive value (NPV). CK 17 might be a good biomarker because of the performance of RT-PCR in detecting mRNA of CK 17 with such high sensitivity and NPV. Further studies using a larger number of OSCC patients and other CKs should be undertaken to establish CK 17 as a useful biomarker. PMID- 17722468 TI - [Educational effects of PBL for students in the Faculty of Dentistry--with special reference to the educational effects on dysphagia--]. AB - PURPOSE: Although the importance of student education has long been emphasized and various educational strategies have been attempted, the PBL method is deemed to be effective among them. Recently, the PBL method was therefore employed in our lecture on dysphagia in order to examine its efficacy. SUBJECTS AND METHODS: Thirty-one female and 35 male students (66 in total, 6th-grade students in the Department of Dentistry) were enrolled in this study which was performed from February 9 to June 29, 2006. The students were allocated into 2 groups, 3-4 per group. Two kinds of educational training program on dysphagia were given by a director/tutor experienced in clinical practice for dysphagia. The first group received a lecture of the conventional type (conventional group), while the latter group received a lecture of PBL (PBL group). In both groups, an identical X-ray film taken during swallowing was evaluated. In addition, the students' impression on the lecture they received was obtained by means of questionnaires. RESULTS: The coincident rate of evaluation on the swallowing image was better in the PBL group than the conventional group on average. Among 23 evaluation items, a coincident rate more than moderate was obtained on 4 and 8 items in the conventional and PBL groups respectively. From the results of the questionnaire survey, it was revealed that the item "motivation" was rated to be significantly better in the PBL than in the conventional group. DISCUSSION: A lecture on dysphagia was given by 2 kinds of educational strategy. From the results of this study, it was revealed that the PBL method was more effective for enhancing the students' motivation on the lecture. In the PBL group, the lecture was given by individual cases with subsequently increased questions and answers and promoted positive participation in the lecture as compared to the conventional group. Furthermore, students' motivation was raised probably due to a good understanding of the case details upon evaluation of the swallowing image with the resultant enhanced rate of coincidence. In order to obtain both educational and enlightening effects simultaneously, an educational program by the PBL method was thus considered to be an effective strategy. PMID- 17722469 TI - [Patient reported outcomes: general principles of development and interpretability]. AB - Direct measurement of how people are feeling and the extent to which they are functioning in daily activities (generally as patient reported outcomes) is critical to judging the benefit of health interventions in chronic conditions. Selection of an appropriate instrument will reflect a comprehensive understanding of the condition of interest and a thorough knowledge of the expected benefits and harms of the proposed intervention. We provide a brief discussion about different ways that health and health measurement have been defined, including the International Classification of Function, Disability and Health (ICF), Health Related Quality of Life (HRQOL) and cost-to-benefit analyses. We outline important properties (reliability, validity, and responsiveness) that a measurement instrument must demonstrate depending on the purpose of measurement, and provide insight as to how to interpret the results of studies that report patient reported outcomes. PMID- 17722470 TI - [Can clinical practice guidelines lead astray?]. PMID- 17722471 TI - [Survival and relapses assessment in patients with Wegener's granulomatosis and predominant renal involvement]. AB - INTRODUCTION: Wegener's granulomatosis (WG) is a potentially fatal condition with remissions and high relapses rates. OBJECTIVES: Assessment of survival and relapses in a population based cohort of patients with WG with predominant renal involvement. PATIENTS AND METHODS: A prospective cohort study including 60 patients--median age of 42 years with different dynamics and clinical presentation. Patients were divided into 3 groups (group 1, group 2 and group 3 respectively, and subgroups: 3.1, 3.2, 3.3): group 1--WG patients without renal involvement, group 2--WG patients with abnormalities in urinary sediment, group 3.1--WG patients with chronic renal failure, group 3.2--WG patients with diffuse alveloar hemorrhage (DAH) and rapid progressive glomerulonephritis (RPGN), and group 3.3--WG patients with RPGN. The clinical analysis has been conducted using the disease extent index (DEl) only and Birmingham Vasculitis Activity Score Wegener's granulomatosis (BVAS-WG) disease activity questionnaire. Logistic regression analysis and the Wilcoxon test were used. Survival time and death risk were assessed using the Kaplan-Meier estimator and Cox proportional hazard model. RESULTS: Eighty-eight percent of patients survived the first year follow-up since the diagnosis, while 84% of patients remained alive after the second year of observation. Life expectancy was 67.1 +/- 4.4 months. During the first year of observation 9.8% of patients died, after 2 years death hazard amounted to 3.7% per year, and after 4 years 2.6% per year (p < 0.05). Death risk was 1.3-fold higher in group 2 and 3.3-fold higher in group 3 compared to group 1 (p > 0.05). Mortality in patients from group 3.1 was 6-fold lower than in patients from group 3.2 (p < 0.03) and in group 3.3 was more than 4-fold lower than in patients from group 3.2 (p < 0.04). Relapse risk after first the year of follow-up was 20% per year and minimally changed after 3 years of observation, then decreased to 6% after 5 years. Relapse hazard ratio in group 2 was significantly lower in comparison with group 1 (HR1/3.6, p < 0.04). CONCLUSIONS: We found significant differences in survival and relapses in various subpopulationsof WG patients. PMID- 17722472 TI - [Angiogenesis in bone marrow of myelodysplastic syndrome patients]. AB - INTRODUCTION: Angiogenesis is an element of physiological and some pathological processes. Recently various investigators have reported that angiogenesis is associated not only with solid tumors but also with hematological malignancies. OBJECTIVES: The aim of this study was to assess angiogenesis in patients with myelodysplastic syndromes. PATIENTS AND METHODS: We have measured bone marrow microvessel density (MVD) in 43 myelodysplastic syndrome (MDS) patients and in 10 subjects of group control--10 lymphoma patients (their bone marrow was free of disease). It was estimated by immunohistochemical method using anti-CD31 and anti CD34 monoclonal antibodies. In 14 MDS patients and 6 healthy donors we also measured serum vascular endothelial growth factor (VEGF) by immunoenzymatic method. RESULTS: Higher MVD numbers were found in MDS patients when compared to control bone marrows. The highest number of MVD was in RAEBt and CMML MDS subtypes according to FAB. There was no correlation between MVD and biological features of MDS patients except for the age (negative correlation). Bone marrow microvessel density does not influenced significantly on overall survival. The serum VEGF concentration in MDS patients was higher than in healthy donors, but the difference was not statistically significant. The VEGF levels did not correlate with MVD. CONCLUSIONS: We concluded that angogenesis is enhanced in bone marrow MDS patients though its mechamism is not yet fully understood. PMID- 17722473 TI - [Two models of thromboprophylaxis in acutely ill medical inpatients]. AB - INTRODUCTION: The risk of venous thromboembolism is equally high in medical patients admitted to the hospital and those treated in the surgery wards. Elderly people, who are immobilized due to heart failure, severe respiratory disease, ischemic stroke and cancer, represent patients at high risk of venous thrombosis. Current recommendations concerning antithrombotic prophylaxis do not specify the duration of prophylaxis in patients treated in the internal wards. OBJECTIVES: The objective of this study was to evaluate the efficacy and safety of two models of thromboprophylaxis with nadroparin in medical inpatients hospitalized for acute illnesses. PATIENTS AND METHODS: A total of 300 consecutive medical patients (155 M, 145 F, mean age, 67.8 +/- 4 years) were randomly assigned in an open-label study to two groups (1:1). Patients received thromboprophylaxis with nadroparin s.c. only during bed immobilization (the first group) or for 10 additional days (the second group). The follow-up lasted for three months after the end of thromboprophylaxis. Proximal deep veins thrombosis of lower limbs and death were considered as endpoints. Adverse effects of thromboprophylaxis were assessed, especially major bleedings and thrombocytopenia. RESULTS: Both groups did not differ with regard to demographic characteristics or thrombotic risk factors. During a further 3-month follow-up of all the 300 patients, death of unknown causes or deep-vein thrombosis were found in 17 (5.6%) patients, including 2 patients who suddenly died. No such events were observed during the thromboprophylaxis period. In medical patients receiving thromboprophylaxis for a longer period of time than the immobilization there was a tendency to lower occurrence of death and deep-vein thrombosis within the first months following hospitalization (12 vs. 5; p = 0.08). There were no major bleedings or thrombocytopenia in both groups during thromboprophylaxis and the subsequent follow-up. CONCLUSIONS: The study confirmed the effectiveness and safety of thromboprophylaxis with nadroparin in acutely ill medical inpatients, suggesting additional benefits from prolonged use of low molecular weight heparins observed during the first months after hospitalization. PMID- 17722474 TI - [Adult patient after correction of tetralogy of Fallot--diagnostic and therapeutic issues]. AB - Over the last 40 years, we have witnessed an impressive revolution in the management of congenital heart disease (CHD). The major factors contributing to this advance include: enhanced diagnostic abilities, improved surgical procedures, sophisticated intensive care and finally better understanding of natural history of CHD. Recent epidemiological studies have documented that although CHD still remains the principal cause o death among infants, a significant increase in the number of patients with heart defects who survive into the adulthood have been observed. Nowadays, for the first time, the number of adults with CHD equals the numbe of children with this defect. Tetralogy of Fallot (TOF) is one of the most frequent congenital cyanotic heart diseases treated with either corrective or palliative surgical techniques. Successful operation followed by specialized care enable patients to have almost normal life expectancy. In the current paper, we have provided the update on the management, diagnostic approach and treatment of adult patients after the TOF correction. Figures present typical problems related to the echocardiographic evaluation. PMID- 17722475 TI - [New therapeutic targets for ACE inhibitors and angiotensin receptor blockers]. AB - Angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) posses multiple beneficial effects such as cardioprotection, cerebroprotection, nephroprotection which provide opportunity to select the most suitable drug for the target vascular bed (e.g. coronary, or cerebral circulation). In some clinical settings, combined therapy ACE-I with ARB (double blockage of the renin-angiotensin-aldosteron system) may appear the most effective. These drugs (especially ARB) may successfully prevent atrial fibrillation and play a protective role in metabolic syndrome. Recently, it has been demonstrated that losartan is able to inhibit vasodilatation of the aorta in Marfan syndrome, which might prevent sudden death due to aorta rupture. An increasing role of ARB is most beneficial in hipotensive therapy (inhibition/regression of hypertension-related organ damage). With particular interest, results of the ONTARGET study are being awaited. This study is focused on the effect of double blockage (ramipril and telmisartan) on reduction of the occurrence of myocardial infarction, stroke, and heart failure. PMID- 17722476 TI - [Administration of iron-containing drugs in non-dialyzed patients with chronic kidney disease]. AB - In the review paper an issue of the administration of iron containing drugs in the treatment of anemia in non-dialyzed patients with chronic kidney disease (CKD) is presented. Iron deficiency in patients with CKD (serum ferritin concentration below 100 ng/ml, transferrin saturation below 20%) occurs in 20-70% of cases. Prevalence of iron deficiency depends on stage of CKD and patients' gender. Among causes of iron deficiency the following reasons are mentioned: blood loss through gastrointestinal tract (17-18% of patients in pre-dialysis stage show positive results of tests on occult blood), diminished absorption (uremic gastroenteropathy, administration of drugs decreasing iron absorption), decreased delivery of food (anorexia, low protein diet), infections and inflammatory state. In the course of infections and inflammatory states body iron storage may be normal, but its utilization for erythropoesis is deteriorated (functional iron deficiency). Results of randomized controlled studies indicate greater efficiency of intravenous therapy in comparison with oral route of iron administration. In practice, the main route of administration of iron-containing drugs to non-dialyzed patients with CKD remains, however, the oral one (iron sulfate, iron fumarate, hem iron) as more convenient and seldom leading to serious side effects. Intravenous iron therapy (iron dextrose, iron polymaltose, sodium-iron gluconate, iron sucrose) is required for cases with absolute deficiency of this microelement, disturbed intestinal absorption, poor tolerance of oral iron medication or its ineffectiveness from other reasons. Administration of erythropoiesis stimulating agents in predialysis period may require intravenous iron therapy because of enhanced consumption of its stores for erythropoiesis. Attention should be paid to possible nephrotoxic effects of administration of iron containing drugs (transient proteinuria, damage of renal tubules, decrease in glomerular filtration rate). PMID- 17722477 TI - [Hypotonia in renal failure patients undergoing dialysis therapy]. AB - In this paper we present the current reviews on the causes, symptoms, prevalence and clinical importance of hypotonia in chronic renal failure patients undergoing dialysis therapy. The results of clinical studies indicate that persistent hypotonia in dialysis patients is associated with increased mortality. PMID- 17722478 TI - [Fasciitis eosinophilica: personal observations and a review of the literature]. AB - Eosinophilic fasciitis is a rare disease that is classified by some authors to scleroderma-like syndromes. Symmetrical induration of skin and subcutaneous tissue associated by eosinophilia in peripheral blood are characteristic features of the disease. Internal organ involvement is uncommon. It is often difficult to diagnose eosinophilic fasciitis and its course may be variable. Glucocorticosteroids are most commonly used in the treatment but in many cases they are ineffective. Then other immunosuppressive therapy must be considered. Prognosis is rather favorable. The remission is not always achieved and sometimes flares of the disease are observed as evidenced by the described cases. It should be emphasized that a majority of our patients were females. In four out of five patients anti-thyreoglobulin antibodies and/or anti-thyroid peroxidase antibodies were present suggesting their involvement in the pathogenesis of eosinophilic fasciitis. Neither indicators of inflammation nor peripheral blood eosinophilia were pathognomonic. Results of glucocorticosteroid treatment were satisfactory in three patients, but two patients required combined immunosuppressive treatment. PMID- 17722479 TI - [Carbamazepine-induced hyponatremia]. AB - Treatment with some drugs may lead to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), the presence of which is more likely in some populations, including people who are elderly or who take diuretics. Resulting drug-induced hyponatremia is often mild and usually resolves following water restriction and withdrawal of the drug. In some patients, however, it may be a potentially fatal condition that is typically asymptomatic until it becomes severe. In this article, we describe the case of a 59-year-old man with arterial hypertension, already treated with hydrochlorothiazide, who presented with hyponatremia after starting administration of carbamazepine. After excluding other common causes of hyponatremia, a diagnosis of SIADH was established, carbamazepine was withdrawn and SIADH treatment introduced. Our study shows that routine assessment of blood electrolytes is reasonable not only in patients receiving diuretics but also in patients treated with other drugs affecting vasopressin secretion. PMID- 17722480 TI - [Edward Korczynski]. AB - This paper is focused on life and scientific achievement of Edward Korczynski, professor of internal diseases in Jagiellonian University, which is seen by many as a pioneer of modern clinic of internal disease in Poland. Korczynski's name is given just aside such great physicians as Joseph Dietl or Tytus Chalubinski. It is due to his works nitroglycerine was introduced into clinical practise, and it is him, who first in the world could diagnose infarct of the heart in a patient, which became classical and canonical in medicine. PMID- 17722481 TI - Some observations on airborne particles in blow-fill-seal filling rooms. AB - Pharmaceutical products produced by blow-fill-seal (BFS) technology are manufactured in clean rooms of different cleanliness classes. Regulatory authorities set requirements on factors such as the maximum allowed airborne particle concentration in filling rooms with BFS machines. To meet the requirements of the authorities, the supply air is HEPA-filtered. The necessary flow of HEPA-filtered air depends on the particle generations from the BFS machines (source strength). One method of reducing the airborne particle concentration in the filling rooms is to install local exhaust systems in order to remove generated particles. Knowledge of particle dispersion and source strength are necessary to enable correctly dimensioned airflows. In this paper, the dispersion pattern of particles was studied at one filling machine. The partial source strength was determined for four different filling machines. The source strength is the total number of airborne particles per second generated by the BFS machine and the process. The value of the partial source strength will be dependent on the efficiency of the local exhaust system. Partial source strength is defined as the estimated theoretical quantity of particles per second emitted from the filling machine into the filling room. The results show that the partial source strength varies widely between the different filling machines. The source strength levels vary between 10(2) and 10(7) particles (> or = 0.5 microm) per second. Furthermore, the results show that the efficiency of the local exhausts can be improved by design adjustments. PMID- 17722482 TI - Microbial ingress through breaches in aseptic manufacturing systems: experimental investigation of pressure-driven leaks of liquids. AB - The ability of pressure-driven leaks to provide an effective barrier against microbial ingress was investigated experimentally. The leak was simulated by circulating growth promoting media through a section of flexible tubing that had a 3/4-inch breach. The flow rate of the media was adjusted until the leak was barely visible; the leak rate was minimized to enhance the possibility of microbial ingress through the breach. The site of the breach was repeatedly inoculated with an actively growing population of Pseudomonas aeruginosa--a highly motile bacterium--suspended in a nutrient-rich medium. The breach was exposed to approximately 140 million organisms over a period of 8 h. This level of contamination greatly exceeds the microbial exposure that a breach would be subjected to in an aseptic manufacturing environment. The data show that microbial ingress did not occur under the above conditions. This indicates that pressure-driven leaks in flexible tubing can provide an effective barrier against microbial ingress, and that the integrity of the sterile boundary can be maintained during such leaks. The results of this investigation could be used to perform risk assessment analyses of the potential for microbial ingress through breaches in aseptic manufacturing systems. PMID- 17722483 TI - Freeze-drying process monitoring using a cold plasma ionization device. AB - A cold plasma ionization device has been designed to monitor freeze-drying processes in situ by monitoring lyophilization chamber moisture content. This plasma device, which consists of a probe that can be mounted directly on the lyophilization chamber, depends upon the ionization of nitrogen and water molecules using a radiofrequency generator and spectrometric signal collection. The study performed on this probe shows that it is steam sterilizable, simple to integrate, reproducible, and sensitive. The limitations include suitable positioning in the lyophilization chamber, calibration, and signal integration. Sensitivity was evaluated in relation to the quantity of vials and the probe positioning, and correlation with existing methods, such as microbalance, was established. These tests verified signal reproducibility through three freeze drying cycles. Scaling-up studies demonstrated a similar product signature for the same product using pilot-scale and larger-scale equipment. On an industrial scale, the method efficiently monitored the freeze-drying cycle, but in a larger industrial freeze-dryer the signal was slightly modified. This was mainly due to the positioning of the plasma device, in relation to the vapor flow pathway, which is not necessarily homogeneous within the freeze-drying chamber. The plasma tool is a relevant method for monitoring freeze-drying processes and may in the future allow the verification of current thermodynamic freeze-drying models. This plasma technique may ultimately represent a process analytical technology (PAT) approach for the freeze-drying process. PMID- 17722484 TI - Preparation and properties of valdecoxib-hydroxypropyl beta-cyclodextrin inclusion complex. AB - Valdecoxib is a non-steroidal anti-inflammatory drug used in the treatment of rheumatoid and osteoarthritis. It is practically insoluble in water. Incidence of adverse events such as nausea has been reported in some trials. Therefore, an attempt was made to improve the aqueous solubility of the drug by making an inclusion complex using hydroxypropyl beta-cyclodextrin (HPbeta-CD). The complexes were prepared by physical mixture and freeze-drying methods. The different methods employed for evaluation--including differential scanning calorimetry, Fourier transform infrared spectral analysis, and scanning electron microscopy studies--indicated complete formation of the complex by the freeze drying method in a molar ratio of 1:1. The prepared complexes showed an improved in vitro dissolution profile and better anti-inflammatory activity as compared to the pure drug. PMID- 17722485 TI - Development of parallel line analysis criteria for recombinant adenovirus potency assay and definition of a unit of potency. AB - Parameter settings of a parallel line analysis procedure were defined by applying statistical analysis procedures to the absorbance data from a cell-based potency bioassay for a recombinant adenovirus, Adenovirus 5 Fibroblast Growth Factor-4 (Ad5FGF-4). The parallel line analysis was performed with a commercially available software, PLA 1.2. The software performs Dixon outlier test on replicates of the absorbance data, performs linear regression analysis to define linear region of the absorbance data, and tests parallelism between the linear regions of standard and sample. Width of Fiducial limit, expressed as a percent of the measured potency, was developed as a criterion for rejection of the assay data and to significantly improve the reliability of the assay results. With the linear range-finding criteria of the software set to a minimum of 5 consecutive dilutions and best statistical outcome, and in combination with the Fiducial limit width acceptance criterion of <135%, 13% of the assay results were rejected. With these criteria applied, the assay was found to be linear over the range of 0.25 to 4 relative potency units, defined as the potency of the sample normalized to the potency of Ad5FGF-4 standard containing 6 x 10(6) adenovirus particles/mL. The overall precision of the assay was estimated to be 52%. Without the application of Fiducial limit width criterion, the assay results were not linear over the range, and an overall precision of 76% was calculated from the data. An absolute unit of potency for the assay was defined by using the parallel line analysis procedure as the amount of Ad5FGF-4 that results in an absorbance value that is 121% of the average absorbance readings of the wells containing cells not infected with the adenovirus. PMID- 17722486 TI - Development of a process control scheme for reduction in weight variation of capsules. AB - This study aims to investigate the causes of different sources of weight variation of capsules and thereby to suggest a suitable control scheme to improve productivity in a pharmaceutical industry. Data are analysed, using the capsule filling process, under a mixed effect cross-nested model. The process capabilities are estimated using Clements' method followed by developing a routine setting and control procedure. PMID- 17722487 TI - Comparative sterilization effectiveness of plasma in O2-H2O2 mixtures and ethylene oxide treatment. AB - We investigated the influence of variable parameters of plasma sterilization and compared its effectiveness with that of ethylene oxide using a reactive ion etching plasma reactor at 13.56 MHz. Gases tested were pure oxygen and oxygen hydrogen peroxide mixtures in 190/10, 180/20, and 160/40 sccm ratios with constant gas flow at 200 sccm, pressure at 0.100 torr, radio-frequency power at 25 W, 50 W, 100 W, and 150 W, and temperature below 60 degrees C. Ethylene oxide sterilization was performed using 450 mg/L at 55 degrees C, 60% humidity, and 0.65 and 0.60 kgf/cm2 pressure. The biological indicator was Bacillus atrophaeus ATCC 9372, with exposure times of 3 to 120 min. Observed D values were 215.91, 55.55, 9.19, and 2.98 min for pure oxygen plasma at 25 W, 50 W, 100 W, and 150 W, respectively. Oxygen-hydrogen peroxide plasma produced D values of 6.41 min (190/10), 6.47 min (180/20), and 4.02 min (160/40) at 100 W and 1.47 min (190/10), 3.11 min (180/20), and 1.94 min (160/40) at 150 W. Ethylene oxide processes resulted in a D value of 2.86 min. Scanning electron microscopy analyses showed damage to the spore cortex. PMID- 17722488 TI - Results of a survey of biological drug and device industries inspected by FDA under the Team Biologics Program. AB - The Product Quality Research Institute, in conjunction with the Food and Drug Administration, conducted an anonymous, electronic survey of the biological products manufacturing industry inspected by Team Biologics, with emphasis in obtaining industry input on inspection and compliance aspects of program operations. Representatives from all of the product-specific manufacturing industries inspected under the Team Biologics Program responded to this survey (vaccines; fractionated plasma proteins and recombinant analogs; allergenics; therapeutics and in-vivo diagnostics; and in-vitro diagnostics, including blood grouping reagents). Data and written feedback was obtained regarding each firm's interactions and experiences of Team Biologics inspections at its facilities over the past three years. The three areas most impacted by Team Biologic inspections were "Production and Process Controls", "Failure Investigations" and "Facility / Equipment Controls". Overall assessment of the program was generally positive with 68% identifying a positive impact on the sites operations and 88% assessed the inspections as being conducted fairly. The findings and conclusions of this report will be utilized by the FDA to evaluate and further assess the impact of the Team Biologics Program and to implement any necessary changes. This report provides useful information to companies currently manufacturing licensed biologic products subject to Team Biologics inspections and also to those companies anticipating these inspections for future product manufacturing. PMID- 17722489 TI - [Prognostic index of acute hepato-cellular damage]. AB - INTRODUCTION: Fulminant hepatic failure is the end result of many different acute damage to the liver. In the present study we compared the clinical to the experimental experience and we postulated the usage of Vascular Endothelial Growth Factor in the clinical arena as a potential treatment in alternative to liver transplantation. MATERIALS AND METHODS: Twelve patient diagnosed with fulminat hepatic failure have been enclosed in the present study. Each patient underwent trans-jugular liver biopsy in order to assess the degree of liver necrosis as well as the following biochemical investigation: AST ALT, Total Bilirubin, _gt, alkaline phosphatase, prothrombin time. RESULTS: Twenty-five percent of those patients required support in the Intensive Care Unit without need for transplantation. Forty-one percent of those patients underwent liver transplantation, and 36% of them died before the liver become available. These results were compared with an experiment, previously performed by our group, where 260 rats were poisoned with CCl4 and subsequently treated with Vascula Endothelial Growth Factor (VEGF). CONCLUSION: The rate of the hepatic regeneration has been found to be critical in the prognosis of patients diagnosed with fulminant hepatic failure. PMID- 17722490 TI - Congenital mammary asymmetry. Classification and surgical treatment. AB - AIM OF THE STUDY: The Authors intend to guide the choice of surgical treatment for mammary asymmetry, according to specific form of asymmetry. MATERIAL AND METHODS: Possible types of symmetryzation surgery are listed. First Author's personal technique is described and some clinical cases are presented. DISCUSSION: Regardless to specific surgical needs for the single case, a generally valid concept is the necessity of a surgical moulding meant to obtain the same volume for both breasts before positioning of implants. This allows a longer lasting symmetry between breasts, as aging modifications bilaterally occur at equal speed if the adipo-glandular structures obtained have the same volume. PMID- 17722491 TI - [Complication of flexible fiberoptic bronchoscopy. Literature review]. AB - INTRODUCTION: Fiberoptic bronchoscopy is the gold standard to study and eventually treat tracheo-bronchial pathology. Performance of fiberoptic bronchoscopy enhances diagnostic precision and has not well documentated risks for the patients. This review examines the international literature of the last 30 yrs about the indication, complications and their prevention during bronchoscopy. MATERIALS AND METHODS: We reviewed by Internet 50 scientific articles, 23 of those were reporting or citing other experiences. We included as metasearch criteria "flexible", "fiberoptic", "bronchoscopy" and "complications" from 1974 to 2006, and as exclusions terms "pediatry", "pregnancy" and "urgency/emergency". Thus, we reported for every complication the incidence range, the characteristics and the indications for the bronchoscopy. DISCUSSION: On 107969 bronchoscopies, the incidence of complication of local anaesthesia was 0.3-0.5%; hypoxiaemia 0.2-21%; arrhythmia 1-10%; post-biopsy bleeding 0.12-7.5%; pneumothorax or pneumomediastinum 1-6%; fever 0.9-2.5%; death 0.1-0.2%. The majority of these complications were not life threatening. CONCLUSIONS: Flexible bronchoscopy is an extremely safe procedure as long as some basic precautions are taken: complications incidence may be reduced by accurate patient selection, correct indication to bronchoscopy with an adequate anaesthesia or analgosedation and the correct endoscope. Is safe and useful virtual bronchoscopy in selected cases. Equipe cooperation and the responsibility of performing endoscopes are basilar. The gain of informed consensus is imperative before the bronchoscopy. PMID- 17722492 TI - [Duodenal perforation post-ERCP: diagnostically and therapeutic management]. AB - OBJECTIVE: Author's experience with periduodenal perforation after ERCP and there systematic approach is presented. METHODS: A retrospective study of 6 instances of duodenal perforation related to endoscopic retrograde cholangiopancreatography. The study follows these parameters: type of perforations, clinical presentation, diagnostic methods, time to diagnosis, methods of management, surgical procedures, length of stay, mortality and morbidity. RESULTS: Traditionally duodenal perforation after ERCP has been managed surgically; however in last decade management has been shifted to a more selective approach, but some authors promotes non surgical routine management: the reported death rate of medical treatment is high as 50%. In our experience an aggressive diagnostically and therapeutically management may reduce mortality. The decision to manage patients without surgery is a dynamic one and should undergo frequent reevaluation whenever the clinical circumstances demonstrate even the slightest untoward development. CONCLUSION: A selective management scheme and an aggressive but selective surgical approach may influence overall mortality. PMID- 17722494 TI - [Severe obesity and insulin resistance. Result obtained by the bilio-pancreatic diversion independentely for an associated gastroresection or gastropreservation]. AB - INTRODUCTION: Type 2 diabetes is the paradigm of an obesity-related disease. In most cases it exists because of the obesity and will disappear with weight loss. AIM OF THIS STUDY: To evaluate the glicemic control in obese patients after two malabsorbitive procedure, the bilio-pancreatic diversion with ad hoc stomach resection (BPD-AHS) and the bilio-pancreatic diversion with transitory gastric restriction (BPD-TGR). MATERIAL AND METHODS: The effect of weight loss following malabsorbitive procedures was studied on 38 patients operated on between the May 1999 and July 2002. Ten patients were diabetes 2 type (group A, 4 patients with oral antidiabetic therapy and 6 with insulin therapy; mean BMI: 49.4 +/- 8.2 Kg/m2), 18 patients were glucose intolerance (group B; mean BMI: 48.2 +/- 6.4 Kg/m2) and 10 patients were in normal glicemic control (group C; mean BMI: 51.2 +/- 8.3 Kg/m2). Five patients in group A were operated on BPD-AHS and 5 patients on BPD-TGR. Ten patients in the group B were operated on BPD-AHS and 8 patients on BPD-TGR. After 3 months from the malabsorbitive procedure group A patients stopped antidiabetic (mean BMI was: 42.3) and group B patients had normal values of glucose and insuline (mean BMI: 41.8). No significant statistically differences were observed in terms of glicemic control, BMI and Excess Weight Loss (EWL%), comparing the two malabsorbitive procedure. RESULTS: Weight loss after both BPD-AHS and BPD-TGR had a beneficial and durable effect on the fasting plasma glucose and serum insuline levels in diabetic and non-diabetic obese patients. The gastric procedure did not change the glicemic control. PMID- 17722493 TI - [Percutaneous US drainage for the treatment of the end abdominal abscesses]. AB - From January 2000 to July 2005 in U.O. Emergency Surgery of Foggia Hospital 40 pz affects by abdominal abscess have been treated (39 post-operative, 1 in diverticulitis) by percutaneous drainage. This treatment has been made only in patients not affects by the serious septic shock, or by wide-spread peritonitis or in the locations to get by to reach by this method. The catheter permanently has been put in 14 pts and the drainage extempore of abdominal abscesses has been made in 26 pts in 28 cases the process cleared up by the one only treatment (6 catheter and 22 percutaneous drainage), in 12 cases has been necessary more drainage treatments (in 4 cases the extempore drainage and in 8 cases the drainage + catheter). One patient has been reoperated because the abscess was intractable by the percutaneous drainage. The serious complications not has been annotated. The persistent slight temperature only has been annoted after the drainage in 3 pts. The percutaneous drainage, consequently, represent a safe, manageable treatment with effectiveness comparable with surgery drainage with less morbility and mortality. PMID- 17722495 TI - [The Boerhaave syndrome. Personal experience]. AB - Boerhaave syndrome is a rare disease with a mortality rate that varies from 10 to 40%. The typical clinical presentation (vomiting, pain, subcutaneuous emphysema) is relatively infrequent. In the case of atypical clinical presentation CT scan with contrast medium administered per os is fundamental for diagnosis. Though there is no general consensus on therapeutic strategies, prognosis is dependent on time interval between onset and diagnosis. We observed four patients with Boerhaave syndrome with an atypical presentation. The time lapse between acute event and diagnosis was less than 6 hours in two cases, 24 hours in one case and 72 hours in the last. All patients presented abdominal pain at admission, preceeded by vomiting in two cases. In all cases diagnosis was carried out by CT scan. All patients were treated surgically: in one case raffia alone was performed, in two cases raffia was associated with temporal bipolar oesophageal exclusion, one case went through oesophageal resection with delayed reconstruction of digestive continuity. One patient with severe COBP died from post-surgical sepsis. One fistula after cervical recanalisation and another after raffia of the oesophageal lesion were successfully treated with endoscopy. We suggest that an aggressive surgical approach is the best treatment for this rare and often severe disease. PMID- 17722496 TI - [Treatment of a large bowel neoplastic obstruction left-sided by self-expanding enteral stent. Personal experience]. AB - The authors report on their experience in the treatment with self-expanding enteral stent for acute left-sided large bowel obstruction and believe that this procedure is effective as a "bridge to surgery". From January to November 2005 3 patients have been treated with colorectal stents in obstructing left-sided large bowel carcinoma: over the following 24 hours we observed canalization and consequent disocclusion of the colonrectum. Stented patients were treated with elective colonic resection with primary anastomosis avoiding decompressive stoma and Hartmann's procedure. PMID- 17722497 TI - [Incarcerated inguinal hernia in elderly: personal tension-free hernioplastic technique]. AB - AIMS OF THE STUDY: With the increasing of the middle age, more and more elderly patients with incarcerated inguinal hernia have to be surgically treated with lower operatory time and lower anesthesiological stress. The Authors present a personal tension-free hernioplastic technique. MATERIALS AND METHODS: Thirthy seven male patients (range 80-92 years) recovered for incarcerated inguinal hernia (Gilbert II tipe) without vascular injury, underwent to tension-free hernioplastic technique without inguinal canal opening, in local anaesthesia. RESULTS: The average operative time was 33 minutes (range 25-42 min). Follow-up at 10 days, 3 months and 5 years shows a correct position of the plug, no recurrence, no alterations of normal testicular vascolarization in absence of paresthesia or chronic pain. The post-operative pain was absent or trascurable whitout the use of any antalgical therapy. PMID- 17722498 TI - Modified Limberg's transposition flap for pilonidal sinus. Long term follow up of 216 cases. AB - AIM OF THIS STUDY: to report our results in a large series of patients with chronic pilonidal sinus (PS) at long term follow up. MATERIALS AND METHODS: Two hundred sixteen patients underwent excision and rhomboid flap transposition (RFT) from 1986 to 2004 for PS, and followed for more than two years. Clinical presentation includes: pilonidal abscess treated by drainage (33%), chronic discharge (48%) and simple infected sinus (19%). Mean follow-up was 74.4 months (range: 24-96). RESULTS: Minimal flap necrosis occurred in 5 pts (2.3%), post operative infection in 2 pts (0.9%), 4 pts (1.8%) had a seroma, 18 pts (8.3%) anesthesia or hypoesthesia on the upper portion of the flap. The mean hospitalization was 3.1 +/- 0.30 days and return to work was 10.8 +/- 2.4 days. Recurrences occurred in 5 pts (7.4%) in our initial 87 pts. Since we modified the technique no recurrences were seen. CONCLUSIONS: The Limberg's technique is a very effective procedure for chronic or recurrent PS with a low complications rate, a short hospital stay, a rapid return to normal activities and a low recurrence rate. Moreover with the modified technique the wound healing and the rate of recurrences have shown a significant decrease. PMID- 17722499 TI - Automatic rupture of unused intraport catheter. Case report. AB - Totally Implantable Central Venous Access Devices (Intraports) are commonly used in cancer patients to administer chemotherapy or parenteral nutrition. These devices are placed by Seldinger technique. We report an unusual case of intraport catheter rupture before the use of the device. The ruptured part of the catheter migrated into the left pulmonary vein via right ventricle. The ruptured part was removed by means of interventional radiology before causing any problems to the patient. All the reported ruptures of port catheters refer to port devices that had been used to administer chemotherapy, fluids, or parenteral nutrition. The unique feature of this case is that the catheter had not been used at all. It is of great interest also the removal of the broken part from the pulmonary vein. PMID- 17722501 TI - [Treatment of esophagopericardial fistula following esophagogastroplasty for esophageal caustic stenosis]. AB - Esophagopericardial fistula is a rare and severe complication, involving several benign, malignant and traumatic pathologies of the esophagus. Only few cases of esophagopericardial fistula have been published so far, as compared to more frequently reported cases of gastropericardial fistula. We report on a 25-year old female with an esophagopericardial fistula following retrosternal esophagogastroplasty for esophageal caustic stenosis. One month before admission to our hospital, the patient had fever and nonradiating substernal chest pain which was relieved by aspirin, unfortunately without adequate antacid therapy. After 3 weeks, for abdominal pain and worsening chest pain with shock, she was admitted to another hospital and underwent laparotomy: an haemoperitoneum was found, due to a rupture of an ovarian cyst which was removed. For persistent shock, the patient had an echocardiogram which revealed a cardiac tamponade, treated with placement of a pericardic drainage (300 cc of purulent liquid). She was then transferred to our unit: an esophageal swallow with a small amount of methilene blue revealed a fistula between the stomach of the esophagogatroplasty and the pericardium. She eventually underwent surgery. A pericardial window was created, the gastric tube was taken down because of the impossibility to suture the gastric ulcer, and an esophagocoloplasty was used for the reconstruction of the alimentary transit. The postoperative course was unevenqf&l. She is alive and well at 15 months after surgery. Esophagopericardial fistula is a rare complication, with a high mortality rate. A timely decision is mandatory and an aggressive treatment often necessary. PMID- 17722500 TI - Intracranial hemorrhage in a HIV patient. Case report and review of the literature. AB - The authors report on a case of a hemophilic male patient, aged 43, HIV positive, HCV positive, who had an episode of intracerebral hemorrhage after a car accident. Intracranial hemorrhage is the most feared complication of hemophilia, especially among HIV positive, who now are considered to be a group at high risk for bleeding. In this report, it is reviewed available data on clinical and imaging features of ICH and the association between ICH and HIV. PMID- 17722502 TI - Perforated jejuneal diverticulosis. Case report and review of literature. AB - Acquired (non-Meckel's) jejunoileal diverticulosis is an uncommon disease, generally characterised by vague and unspecific symptoms. This rare condition is mainly expressed as acute complications: gastrointestinal haemorrhage, mechanic obstruction of the small intestine or perforated diverticulum, requiring urgent surgical intervention. The authors report a case of this unusual clinical occurrence characterized by a picture of abdominal pain due to perforation of jejuneal diverticulum. The final etiological diagnosis was possible only during surgery. PMID- 17722503 TI - [Hemorrhagic shock caused by iatrogenic aorto-cava injury. Case report]. AB - INTRODUCTION: Vascular injuries during lumbar disc surgery vary between 1 and 5 per 10,000 disc operations and usually represent life-threatening events. MATERIAL AND METHODS: The authors present a case of aorto-iliac and ICY laceration during lumbar disc hernia repair, successfully treated with immediate damage control and direct suture, followed by endovascular procedure. CASE REPORT: A 34-year-old lady was operated on for a symptomatic disc herniation at L4-L5. Shortly after this procedure, an ipovolemic shock (IV degree) suddenly occurred with an evident abdominal distension. An emergent laparotomy in the same neurosurgery OR was then performed and revealed an active haemorrhage arising fJom an expansive retroperitoneal bleeding at the level of aorto-iliac bifurcation. After a proximal and distal damage control (manual compression plus aortic clamping) aortic and caval lacerations were repaired. An abdominal packing completed the procedure, due to the concomitant coagulopathy applied. At the second surgical look, carried out 24 hours after the first procedure, no active bleeding or vascular impairment were detected but an intraoperative US examination revealed a 3.5 cm wide right iliac pseudoaneurism confirmed by angioCT scan. This pseudoaneurism was later successfully treated with a double endovascular stenting. Postoperative outcome was uneventful and the patient was then discharged 11 days after the discectomy. Follow up study at 2 years did not demonstrate significant sequels. CONCLUSION: Although rare, vascular injuries during lumbar disc hernia surgery, are extremely severe complications, leading to high morbidity and mortality rates. In case of massive bleeding the presence of an "intrahospital" trauma team is a crucial factor for life-saving. PMID- 17722504 TI - IJN's second year is now a part of nanomedicine history! PMID- 17722505 TI - Targeting nanomedicines in the treatment of rheumatoid arthritis: focus on certolizumab pegol. AB - Anti-TNFalpha therapy has revolutionized the treatment of rheumatoid arthritis (RA) and other inflammatory diseases. These drugs are powerful and expensive. A new anti-TNFalpha agent, a nanomolecule comprising a humanized Fab' antibody fragment against TNFalpha with a polyethylene glycol tail, is shortly to complete phase III trials in RA. In this review we will discuss the construct of this new molecule, data from trials so far, and its potential place in the market place. PMID- 17722506 TI - Single-dose azithromycin microsphere formulation: a novel delivery system for antibiotics. AB - Azithromycin extended release (Zmax, Pfizer Inc) is a novel single-dose administration formulation of azithromycin which won FDA approval in June 2005 and is currently approved for the treatment of community acquired pneumonia and acute bacterial sinusitis. Azitromycin is incorporated into sustained-release microspheres which release the drug slowly through 200 microm pores. Because of this sustained release mechanism, most of the drug is released into the lower gastrointestinal tract, reducing gastrointestinal side-effects, and allowing for a higher dose to be administered. The unique pharmacological properties and extremely long half-life of azithromycin make this drug well suited to single dose administration but gastrointestinal side effects have previously hampered single-dose therapy. PMID- 17722507 TI - Nanomedicines in the treatment of emesis during chemotherapy: focus on aprepitant. AB - Aprepitant, a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors, is the active ingredient of EMEND which has recently been approved by the FDA for the prevention of chemotherapy-induced nausea and vomiting (CINV). Aprepitant undergoes extensive metabolism, primarily via CYP3A4 mediated oxidation. It is eliminated primarily by metabolism and is not renally excreted. The apparent terminal half-life in humans ranged from 9 to 13 hours. Early development studies led to the development of a nanoparticle formulation to enhance exposure and minimize food effects. Two large randomized trials accruing 1099 patients studied the effect in patients receiving cisplatin of adding aprepitant to ondansetron and dexamethasone on day 1 then to dexamethasone on days 2 and 3 to control delayed emesis. The complete response of no vomiting and no rescue medication overall from days 1 to 5 improved from 48% to 68% (p<0.001), a 13% improvement in acute emesis but a 21% improvement in delayed emesis with the improvement from 51% to 72% (p<0.001). Similarly, 866 patients treated with cyclophosphamide plus either doxorubicin or epirubicin, received either ondansetron, dexamethasone, and aprepitant on day 1 followed by aprepitant on days 2 and 3 or ondansetron and dexamethasone on day 1 and dexamethasone on days 2 and 3. The overall complete response rate over 5 days was better for the aprepitant group 50.8% vs 42.5% (p=0.015). Complete responses were reported in more patients taking aprepitant in both the acute (76% vs 69%, p=0.034) and delayed (55% vs 49%, p=0.064) phases of vomiting. There were no clinically relevant differences in toxicity by adding aprepitant and improvements in the quality of life of patients on chemotherapy were recorded. PMID- 17722508 TI - Nanomedicines in the treatment of chronic hepatitis C--focus on pegylated interferon alpha-2a. AB - Nanotechnology is the application of nanotechnology within medicine. An illustration of this is the use of pegylation as a means of modifying naturally occurring proteins which may have clinical applications, in order to improve the pharmacodynamics of the protein resulting in an effective medication. An example of this is pegylated interferon. The purpose of this review is to examine the chemistry, clinical pharmacology, pharmacokinetics, pharmacodynamics, and clinical studies with 40 kDa pegylated interferon to illustrate the general principles of pegylated biological proteins. The use in clinical practice is reviewed along with the evidence for both efficiacy, safety, and advantages over standard interferon. PMID- 17722510 TI - Nanomedicines in the treatment of anemia in renal disease: focus on CERA (Continuous Erythropoietin Receptor Activator). AB - Anemia is a common complication of chronic kidney disease (CKD), with erythropoietin deficiency being the major contributing factor. The availability of erythropoiesis-stimulating agents (ESAs) has been a seminal advance in the treatment of anemia related to chronic kidney disease. Over the course of the last decade and a half, newer generations of ESAs have become available. The first-generation ESAs or epoetins have a relatively shorter half-life and have traditionally been administered up to 3 times per week intravenously or subcutaneously to maintain adequate hemoglobin (Hb) levels. At the turn of the century, darbepoetin alfa, a hyperglycosylated form, became available for clinical use. It conferred greater metabolic stability in vivo owing to two additional N-linked carbohydrate chains attached to the protein backbone and has a half-life 3 times longer than that of epoetin. Recently developed and undergoing phase III clinical trials is the third-generation ESA, Continuous Erythropoiesis Receptor Activator (CERA), which has a methoxy-polyethylene glycol polymer chain integrated and has a longer elimination half-life than the first- and second-generation ESAs. Its receptor binding characteristics also differ from those of previous ESAs. Its major advantage is that extended dosing intervals are possible in the management of anemia related to erythropoietin deficiency. PMID- 17722509 TI - Nanomedicines in renal transplant rejection--focus on sirolimus. AB - Nanomedicine, known as the application of nanotechnology in medicine, has been applied to overcome the problems of poor bioavailability, in vitro and in vivo stability, and targeted delivery in the preparation of pharmaceutical products. Sirolimus, a water-insoluble immunosuppressant, has been formulated into an oral solid dosage form by using NanoCrystal technology to increase the water solubility and thereby the bioavailability. The efficacy, safety, and pharmacokinetic properties are not significantly different between liquid and solid formulations except that less fluctuation of sirolimus blood concentration was observed in solid dosage form. The tablet formulation offers the advantages of better palatability and more convenience for long-term use. Sirolimus tablets are not only a successful example of nanomedicine, but also a more cost-effective treatment in renal transplantation than cyclosporine and tacrolimus. PMID- 17722511 TI - Targeting nanomedicines in the treatment of Crohn's disease: focus on certolizumab pegol (CDP870). AB - A variety of targets for therapeutic intervention are based upon advances in understanding of the immunopathogenesis of Crohn's disease. Crohn's disease is initiated by an innate immune response, which eventuates in a T-cell driven process, characterized by a T-helper cell 1 type cytokine profile. Several new treatments now focus on suppressing T-cell differentiation or T-cell inflammation. Since inflammatory bowel disease (IBD) represents a state of dysregulated inflammation, drugs that augment the anti-inflammatory response have the potential to downregulate inflammation and thereby hopefully modify the disease. Tumour necrosis factor (TNF) is a major target of research and clinical investigation. TNF has proinflammatory effects in the intestinal mucosa and is a pivotal cytokine in the inflammatory cascade. Certolizumab pegol (CDP870) is a PEGylated, Fab' fragment of a humanized anti-TNF-alpha monoclonal antibody. PEGylation increases the half-life, reduces the requirement for frequent dosing, and possibly reduces antigenicity as well. Certolizumab has been shown in Phase III trials to achieve and maintain clinical response and remission in Crohn's disease patients. It improves the quality of life. Certolizumab pegol will be indicated for moderately to severely active Crohn's disease, but it is not yet licensed in Europe or the US. It is not possible to construct an algorithm for treatment, but when compared with infliximab the two principal advantages are likely to be lower immunogenicity (as shown by anti-drug antibodies, absence of infusion reactions, and low rate of antinuclear antibodies), and a subcutaneous route of administration. These two factors may be sufficient to promote it up the pecking order of anti-TNF agents. PMID- 17722512 TI - Oral transmucosal fentanyl citrate in cancer pain management: a practical application of nanotechnology. AB - Pain is experienced by most cancer patients and represents an important issue in the clinical setting. Breakthrough pain is a transitory flare of pain that occurs in most cancer patients on a background of otherwise controlled persistent pain. Treatment of breakthrough pain is a challenging phenomenon. Oral transmucosal fentanyl citrate (OTFC; Actiq, Cephalon, UK), a new opioid formulation with a unique delivery system, utilizing the advantages that nanotechnology offers, reflects the characteristics of breakthrough pain (rapid onset of action and short duration), which makes it an effective treatment to cancer patients who are already receiving opioids and continue to experience such flares of pain. Oral transmucosal fentanyl citrate is specifically developed and approved for the management of breakthrough pain in cancer patients and it has the potential to be a useful tool for clinicians. PMID- 17722513 TI - Fluocinolone acetonide intravitreal sustained release device--a new addition to the armamentarium of uveitic management. AB - Uveitis is a potentially sight-threatening inflammatory eye disease caused by multiple infectious and non-infectious etiologies for which the standard of care involves corticosteroids or various immunomodulary therapy (IMT) drugs. These available treatments, although effective, may cause significant morbidity and sometimes mortality in uveitis patients due to their toxic side-effects and the necessity of long-term therapy to prevent recurrences. In order to avoid the systemic toxicity ofcorticosteroids and IMT or the repeated injections of local steroids necessary to control ocular inflammation, and to prevent development of cumulative damage resulting from recurrent episodes of inflammation, researchers have developed a number of local corticosteroid sustained-release devices that can be implanted directly into the vitreous of the eye, at the site of the inflammatory disease. Preliminary studies of such a device, the fluocinolone acetonide (Retisert) implant, have shown significant reductions in the number of inflammatory episodes and decreased reliance on systemic corticosteroids or other IMT. This review explores the current research evaluating the fluocinolone sustained-release intravitreal implant in the treatment of posterior uveitis and the implications for its future use on a wider scale. PMID- 17722515 TI - Motexafin gadolinium injection for the treatment of brain metastases in patients with non-small cell lung cancer. AB - Despite recent advances in technology, targeting, and chemotherapy, brain metastasis from non-small cell lung cancer (NSCLC) remains a significant problem. The vast majority of patients with this diagnosis undergo whole brain radiation therapy (WBRT). However, outcomes are still quite poor with median survivals measured in only months. In an effort to enhance outcomes from external beam radiation treatments, radiosensitizers have been investigated. Motexafin gadolinium (MGd) (Xcytrin, Sunnyvale, CA, USA) is a novel radiation sensitizer with a unique mechanism of action that may increase the therapeutic index of WBRT for patients with brain metastases, particularly in those with NSCLC histologies. Here we review the rationale for the use of this drug as well as its current and future role as a radiation enhancer in the management of NSCLC brain metastasis. PMID- 17722514 TI - Age-related macular degeneration: a target for nanotechnology derived medicines. AB - Despite the fact that the retina is a fairly accessible portion of the central nervous system, there are virtually no treatments for early age-related macular degeneration (AMD). AMD is a degenerative retinal disease that causes progressive loss of central vision and is the leading cause of irreversible vision loss and legal blindness in individuals over the age of 50. Both environmental and genetic components play a role in its development. AMD is a multifactorial disease with characteristics that include drusen, hyperpigmentation and/or hypopigmentation of the retinal pigment epithelium (RPE), geographic atrophy and, in a subset of patients, late-stage choroidal neovascularization (CNV). Drugs that inhibit vascular endothelial growth factor (VEGF) have proven effective in treating late stage CNV, but optimal means of drug delivery remains to be determined. Microscopic particles, whose size is on the nanometer scale, show considerable promise for drug delivery to the retina, for gene therapy, and for powering prosthetic "artificial retinas." This article summarizes the pathophysiology of AMD stressing potential applications from nanotechnology. PMID- 17722516 TI - Synthesis and characterization of nanoscale dendritic RGD clusters for potential applications in tissue engineering and drug delivery. AB - Spatial control over the distribution and the aggregation of arginine-glycine aspartate (RGD) peptides at the nanoscale significantly affects cell responses. For example, nanoscale clustering of RGD peptides can induce integrins to cluster, thus triggering complete cell signaling. Dendrimers have a unique, highly branched, nearly spherical and symmetrical structure with low polydispersity, nanoscale size, and high functionality. Therefore, dendrimers are a class of ideal scaffold for construction of nanoscale dendritic RGD clusters in which RGD loading degree and cluster size can be finely adjusted. This new type of nanoscale dendritic RGD cluster will aid us to better understand the impact of spatial arrangement of RGD on cellular responses and to engineer RGD to trigger more favorable cellular responses. In this study, nanoscale dendritic RGD clusters were synthesized based on Starburst anionic G3.5 and cationic G4.0 polyamidoamine (PAMAM) dendrimers. The multiple terminal functional groups on the outermost layer of the dendrimer were coupled with RGD tripeptides. Biofunctionalized dendrimer structures were found to be highly dependent on the generation and the extent of peptide modification (ie, number of peptides per PAMAM dendrimer). Fluorescein isothiocyanate (FITC)-conjugated PAMAM dendrimers were utilized to monitor cellular internalization of dendrimers by adherent fibroblasts. Anionic G3.5-based dendritic RGD clusters have been shown to have no negative effect on fibroblast viability and a concentration-dependent effect on lowering cell adhesion on tissue culture polystyrene (TCPS) as that of free RGD. A similar concentration-dependent effect in cell viability and adhesion was also observed for cationic G4.0-based dendritic RGD clusters at lower but not at high concentrations. The results imply that the synthesized nanoscale dendritic RGD clusters have great potential for tissue engineering and drug delivery applications. PMID- 17722517 TI - High performance DNA nano-carriers of carbonate apatite: multiple factors in regulation of particle synthesis and transfection efficiency. AB - Increasing attention is being paid on synthetic DNA delivery systems considering some potential life-threatening effects of viral particles, for development of gene-based nanomedicine in the 21st century. In the current nonviral approaches, most of the efforts have been engaged with organic macromolecules like lipids, polymers, and peptides, but comparatively fewer attempts were made to evaluate the potential of inorganic materials for gene delivery. We recently reported that biodegradable nanoparticles of carbonate apatite are highly efficient in transfecting a wide variety of mammalian cells. Here we show that a number of parameters actively regulate synthesis of the nanoparticles and their subsequent transfection efficacy. Development of "supersaturation", which is the prerequisite for generation of such particles, could be easily modulated by reactant concentrations, pH of the buffered solution, and incubation temperatures, enabling us to establish a flexible particle generation process for highly productive trans-gene delivery. Carbonate incorporation into the particles have been proposed for generating nano-size particles resulting in cellular uptake of huge amount of plasmid DNA as well as endosome destabilization facilitating significant release of DNA from the endosomes. PMID- 17722519 TI - Bioconjugated nanoparticle detection of respiratory syncytial virus infection. AB - The integration of nanotechnology with biology has produced major advances in molecular diagnostics, therapeutics, and bioengineering. Recent advances have led to the development of functionalized nanoparticles (NPs) that are covalently linked to biological molecules such as antibodies, peptides, proteins, and nucleic acids. These functionalized NPs allow for development of novel diagnostic tools and methods, particularly for pathogens, as rapid and sensitive diagnostics are essential for defining the emergence of infection, determining the period that preventive measures should be applied, for evaluating drug and vaccine efficacy, and for controlling epidemics. In this study, we show that functionalized NPs conjugated to monoclonal antibodies can be used to rapidly and specifically detect respiratory syncytial virus in vitro and in vivo. These results suggest that functionalized NPs can provide direct, rapid, and sensitive detection of viruses and thereby bridge the gap between current cumbersome virus detection assays and the burgeoning need for more rapid and sensitive detection of viral agents. PMID- 17722520 TI - Retrospective study of factors affecting non-healing of wounds during hyperbaric oxygen therapy. AB - OBJECTIVE: To identify potential factors, including cigarette smoking and diabetes status, that affect wound-healing outcomes during a six-week course of hyperbaric oxygen therapy (HBOT). METHOD: Seventy-three patients with 85 non healing lower extremity wounds were treated with hyperbaric oxygen therapy (100% oxygen, 2.4 atmosphere absolute, (ATA), for 90 minutes). The wound area was evaluated over the six-week treatment period. RESULTS: A non-hierarchical clustering analysis of normalised wound-area data revealed that healing responses could be segregated into three groups: robust healing (n=31, over 50% reduction in area), minimal healing (n=33, 15% reduction) and non-healing (n=21,60% increase in area). Further analysis revealed that cigarette smoking was associated with poor response (p<0.0001), whereas diabetes was not. Robust responders had higher blood levels of creatinine and urea nitrogen, increased peripheral oxygenation (TcpO2), and were younger than less responsive patients. CONCLUSION: The results suggest that response to HBOT is variable and some patients do not benefit from it. Clinicians should evaluate available laboratory values, age and social history to determine if a patient is likely to benefit from HBOT. PMID- 17722518 TI - Neurite development in PC12 cells cultured on nanopillars and nanopores with sizes comparable with filopodia. AB - We investigated the effect ofnanoscale topography on neurite development in pheochromocytoma (PC12 cells) by culturing the cells on substrates having nanoscale pillars and pores with sizes comparable with filipodia. We found that cells on nanopillars and nanopores developed fewer and shorter neurites than cells on smooth substrates, and that cells on nanopores developed more and longer neurites than cells on nanopillars. These results suggest that PC12 cells were spatially aware of the difference in the nanoscale structures of the underlying substrates and responded differently in their neurite extension. This finding points to the possibility of using nanoscale topographic features to control neurite development in neurons. PMID- 17722521 TI - The effects of onion extract on hypertrophic and keloid scars. AB - OBJECTIVE: To evaluate the therapeutic activity of topical onion extract in gel form on hypertrophic and keloid scars, focusing on problems such as elevation, redness, hardness, itching and pain. METHOD: This comparative prospective study assigned 60 patients to three groups. Group I was treated with onion extract alone, group 2 with silicon gel sheet alone and 3 group with a combination of onion extract and silicon gel sheet. RESULTS: In the group comparisons, a significant difference was observed at the end of six months in the colour parameter between group I and group 2 and in the height parameter between group I and group 3 (ANOVA post-hoc Tukey's test, p<0.01 and p<0.05 respectively). The onion extract was more effective in relation to scar colour, while the silicon gel sheet was superior in decreasing the height of scar (paired sample t-test, p<0.001). In addition, the most effective therapeutic results were obtained when the silicon gel sheet treatment was combined with onion extract in group 3. CONCLUSION: Onion extract improved hypertrophic and keloids scars via multiple mechanisms. However, it was statistically ineffective in improving scar height and itching. For this reason, onion extract therapy should be used in combination with an occlusive silicon dressing to achieve a satisfying decrease in scar height. PMID- 17722522 TI - The influence of essential oils on the process of wound healing: a review of the current evidence. AB - This paper reports on a literature review of evidence on the influence of essential oils on wound healing and their potential application in clinical practice. It focuses mainly on tea tree, lavender, chamomile, thyme and ocimum oils. PMID- 17722523 TI - A prospective study on the use of a non-adhesive gelling foam dressing on exuding leg ulcers. AB - OBJECTIVE: This non-comparative phase II study aimed to evaluate the safety and performance of a non-adhesive gelling foam dressing (GFD-N) in leg ulcer management. METHOD: Forty-six subjects with moderately to heavily exuding leg ulcers were treated with a regimen including GFD-N. Dressings were changed at least every seven days for four weeks or until healing. RESULTS: Mean GFD-N wear time was 3.2 days per subject. Mean wound area decreased from 10.1 cm2 at baseline to 5.1 cm2 at four weeks (p<0.001) and healed in five subjects (11%). The surrounding skin improved or remained stable in all but one subject. When compared with pre-study dressings, ulcer pain decreased for GFD-N, both with the dressing in place (p<0.001) and on dressing removal (p<0.001). Of final investigator ratings for 45 subjects, most were 'excellent' for ease of application (89%), ease of removal (96%), conformability (67%) and overall performance (58%). Five subjects experienced adverse events; none were serious or dressing-related. CONCLUSION: This small study demonstrates that GFD-N was safe, effective and convenient for wound healing, exudate management, pain/comfort and ease of use. PMID- 17722524 TI - The endotoxin binding and antioxidative properties of ceramic granules. AB - OBJECTIVE: To investigate the possible antimicrobial activities and the detoxification (endotoxin binding and free radical scavenging) properties of Cerdak. METHOD: In order to measure the antimicrobial activity of Cerdak, microorganisms were separately inoculated into nutrient agar in the presence of Cerdak, and growth was observed over 48 hours. Cerdak was incubated with 4000EU/ml endotoxin, and the residual endotoxin was determined over 24 hours. The decrease in the colour of ABTS and DPPH (inorganic free radicals) in the presence of Cerdak was colourimetrically monitored as a measure of Cerdax's free radical scavenging ability. DNA was exposed to hydrogen peroxide and ultraviolet irradiation in the presence and absence of Cerdak. The DNA strand break was then observed through electrophoresis. RESULTS: While Cerdak had little or no antibacterial activities, it demonstrated a high water and endotoxin-binding capacity. It also protected DNA from damage by reactive oxygen species. CONCLUSION: The detoxification properties of Cerdak could contribute to its healing abilities. PMID- 17722525 TI - Role of diabetic microvascular disease in the development of foot wounds. AB - The influence of microvascular changes in diabetic foot tissue breakdown is not fully known. Research on the role of vascular mediators in diabetes and their effect on the microvasculature may help to create a more unified theory. PMID- 17722526 TI - Minority workers remain confident about retirement, despite lagging preparations and false expectations. PMID- 17722527 TI - Nanomedicine: what's in a definition? PMID- 17722528 TI - Chitosan nanoparticles for oral drug and gene delivery. AB - Chitosan is a widely available, mucoadhesive polymer that is able to increase cellular permeability and improve the bioavailability of orally administered protein drugs. It can also be readily formed into nanoparticles able to entrap drugs or condense plasmid DNA. Studies on the formulation and oral delivery of such chitosan nanoparticles have demonstrated their efficacy in enhancing drug uptake and promoting gene expression. This review summarizes some of these findings and highlights the potential of chitosan as a component of oral delivery systems. PMID- 17722530 TI - Immunonanoshells for targeted photothermal ablation of tumor cells. AB - Consisting of a silica core surrounded by a thin gold shell, nanoshells possess an optical tunability that spans the visible to the near infrared (NIR) region, a region where light penetrates tissues deeply. Conjugated with tumor-specific antibodies, NIR-absorbing immunonanoshells can preferentially bind to tumor cells. NIR light then heats the bound nanoshells, thus destroying the targeted cells. Antibodies can be consistently bound to the nanoshells via a bifunctional polyethylene glycol (PEG) linker at a density of approximately 150 antibodies per nanoshell. In vitro studies have confirmed the ability to selectively induce cell death with the photothermal interaction of immunonanoshells and NIR light. Prior to incubation with anti-human epidermal growth factor receptor (HER2) immunonanoshells, HER2-expressing SK-BR-3 breast carcinoma cells were seeded alone or adjacent to human dermal fibroblasts (HDFs). Anti-HER2 immunonanoshells bound to HER2-expressing cells resulted in the death of SK-BR-3 cells after NIR exposure only within the irradiated area, while HDFs remained viable after similar treatment since the immunonanoshells did not bind to these cells at high levels. Control nanoshells, conjugated with nonspecific anti-IgG or PEG, did not bind to either cell type, and cells continued to be viable after treatment with these control nanoshells and NIR irradiation. PMID- 17722531 TI - Efficient suppression of secretory clusterin levels by polymer-siRNA nanocomplexes enhances ionizing radiation lethality in human MCF-7 breast cancer cells in vitro. AB - Small interfering RNA molecules (siRNA) hold great promise to specifically target cytoprotective factors to enhance cancer therapy. Like antisense RNA strategies, however, the use of siRNA is limited because of in vivo instability. As a first step to overcome delivery issues, a series of graft copolymers of polyethylene glycol and polyethylenimine (PEI-g-PEG) were synthesized and investigated as nontoxic carriers for delivery of siRNA targeting the signaling peptide of secretory clusterin (sCLU), a prosurvival factor that protects cells from ionizing radiation (IR) injury, as well as chemotherapeutic agents. Three copolymers with different PEG grafting densities were tested for their abilities to bind and form nanocomplexes with siRNA. A copolymer composed of 10 PEG grafts (2 kDa each) per PEI polymer (2k10 copolymer) gave the highest binding affinity to siRNA by ethidium bromide exclusion assays, and had the smallest nanocomplex size (115 +/- 13 nm diameter). In human breast cancer MCF-7 cells, 2k10-siRNA sCLU nanocomplexes suppressed both basal as well as IR-induced sCLU protein expression, which led to an over 3-fold increase in IR-induced lethality over 2k10-siRNA scrambled controls. In summary, this study demonstrates the proof-of principle in using nanoparticle-mediated delivery of specific siRNAs to enhance the lethality of IR exposure in vitro, opening the door for siRNA-mediated knockdown of specific cytoprotective factors, such as DNA repair, anti-apoptotic, free radical scavenging, and many other proteins. PMID- 17722532 TI - Immobilization of cells by electrostatic droplet generation: a model system for potential application in medicine. AB - The process of electrostatic extrusion as a method for cell immobilization was investigated that could be used for potential applications in medicine. An attempt was made to assess the effects of cell addition and polymer concentration on the overall entrapment procedure, ie, on each stage of immobilization: polymer cell suspension rheological characteristics, electrostatic extrusion process, and the process ofgelation. The findings should contribute to a better understanding of polymer-cell interactions, which could be crucial in possible medical treatments. Alginate-yeast was used as a model system for carrier-cells. The electrostatic extrusion was considered as a complex two-phase flow system and the effects of cell and alginate concentrations on the resulting microbead size and uniformity were assessed. Under investigated conditions, microbeads 50-600 microm in diameter were produced and the increase in both alginate and cell concentrations resulted in larger microbeads with higher standard deviations in size. We attempted to rationalize the findings by rheological characterization of the cell-alginate suspensions. Rheological characterization revealed non Newtonian, pseudoplastic behavior of cell-alginate suspensions with higher viscosities at higher alginate concentrations. However, the presence of cells even at high concentrations (5x10(8) and 1x10(9) cells/mL) did not significantly affect the rheological properties of Na-alginate solution. Lastly, we investigated the kinetics of alginate gelation with respect to the quantity of Ca2+ ions and cell presence. The gelation kinetics were examined under conditions of limited supply with Ca2+ ions, which can be essential for immobilization of highly sensitive mammalian cells that require minimal exposure to CaCl2 solution. The molar ratio of G units to Ca2+ ions of 3.8:1 provided complete crosslinking, while the increase in alginate concentration resulted in prolonged gelation times but higher strength of the resulting gel. The cell presence decreased the rate of network formation as well as the strength of the obtained Ca-alginate hydrogel. PMID- 17722533 TI - Efficient gene transfection using chitosan-alginate core-shell nanoparticles. AB - Reverse microemulsion was used as a template to fabricate chitosan-alginate core shell nanoparticles encapsulated with enhanced green fluorescent protein (EGFP) encoded plasmids. The average size of DNA-entrapped nanoparticles measured by dynamic light scattering was increased proportionally, with the N/P ratios ranging from 5 to 20. These alginate-coated chitosan nanoparticles endocytosed by NIH 3T3 cells trigged swelling of transport vesicles which render gene escape before entering digestive endolysosomal compartment and concomitantly promote gene transfection rate. Results showed that DNA-encapsulated chitosan-alginate nanoparticles with average size of 64nm (N/P ratio of 5) could achieve the level of gene expression comparable with the one obtained by using polyethyleneimine DNA complexes. PMID- 17722534 TI - Chitosan and lactic acid-grafted chitosan nanoparticles as carriers for prolonged drug delivery. AB - Nanoparticles of approximately 10nm in diameter made with chitosan or lactic acid grafted chitosan were developed for high drug loading and prolonged drug release. A drug encapsulation efficiency of 92% and a release rate of 28% from chitosan nanoparticles over a 4-week period were demonstrated with bovine serum protein. To further increase drug encapsulation, prolong drug release, and increase chitosan solubility in solution of neutral pH, chitosan was modified with lactic acid by grafting D,L-lactic acid onto amino groups in chitosan without using a catalyst. The lactic acid-grafted chitosan nanoparticles demonstrated a drug encapsulation efficiency of 96% and a protein release rate of 15% over 4 weeks. With increased protein concentration, the drug encapsulation efficiency decreased and drug release rate increased. Unlike chitosan, which is generally soluble only in acid solution, the chitosan modified with lactic acid can be prepared from solutions of neutral pH, offering an additional advantage of allowing proteins or drugs to be uniformly incorporated in the matrix structure with minimal or no denaturization. PMID- 17722535 TI - MC3T3-E1 osteoblast attachment and proliferation on porous hydroxyapatite scaffolds fabricated with nanophase powder. AB - Porous bone tissue engineering scaffolds were fabricated using both nano hydroxyapatite (nano HA) powder (20 nm average particle size) and micro HA powder (10 microm average particle size), resulting in sintered scaffolds of 59 vol% porosity and 8.6 +/- 1.9 microm average grain size and 72 vol% porosity and 588 +/- 55nm average grain size, respectively. Scanning electron microscopy was used to measure both the grain size and pore size. MC3T3-E1 osteoblast (OB) attachment and proliferation on both nano HA and micro HA porous scaffolds were quantified. As expected, OB cell number was greater on nano HA scaffolds compared with similarly processed micro HA scaffolds 5 days after seeding, while OB attachment did not appear greater on the nano HA scaffolds (p < 0.05). PMID- 17722529 TI - Fenofibrate: a novel formulation (Triglide) in the treatment of lipid disorders: a review. AB - Cardiovascular disease is the major cause of mortality worldwide and accounts for approximately 40% of all deaths. Dyslipidemia is one of the primary causes of atherosclerosis and effective interventions to correct dyslipidemia should form an integral component of any strategy aimed at preventing cardiovascular disease. Fibrates have played a major role in the treatment of hyperlipidemia for more than two decades. Fenofibrate is one of the most commonly used fibrates worldwide. Since fenofibrate was first introduced in clinical practice, a major drawback has been its low bioavailability when taken under fasting conditions. Insoluble Drug Delivery-Microparticle fenofibrate is a new formulation that has an equivalent extent of absorption under fed or fasting conditions. In this review, we will discuss the clinical pharmacology of fenofibrate, with particular emphasis on this novel formulation, as well as its lipid-modulating and pleiotropic actions. We will also analyze the major trial that evaluated fibrates for primary and secondary prevention of cardiovascular disease, the safety and efficacy profile of fibrate-statin combination treatment, and the current recommendations regarding the use of fibrates in clinical practice. PMID- 17722536 TI - Multiplexed microsphere diagnostic tools in gene expression applications: factors and futures. AB - Microarrays have received significant attention in recent years as scientists have firstly identified factors that can produce reduced confidence in gene expression data obtained on these platforms, and secondly sought to establish laboratory practices and a set of standards by which data are reported with integrity. Microsphere-based assays represent a new generation of diagnostics in this field capable of providing substantial quantitative and qualitative information from gene expression profiling. However, for gene expression profiling, this type of platform is still in the demonstration phase, with issues arising from comparative studies in the literature not yet identified. It is desirable to identify potential parameters that are established as important in controlling the information derived from microsphere-based hybridizations to quantify gene expression. As these evolve, a standard set of parameters will be established that are required to be provided when data are submitted for publication. Here we initiate this process by identifying a number of parameters we have found to be important in microsphere-based assays designed for the quantification of low abundant genes which are variable between studies. PMID- 17722539 TI - Selective placement of templated DNA nanowires between microstructured electrodes. AB - Dip-pen nanolithography is used to selectively modify the SiOx area between microfabricated electrodes. The modified surface is characterized by atomic force microscopy, X-ray photoelectron spectroscopy, force volume imaging, and adhesion maps. The functionalized complex architecture is used for the localization of DNA coated with magnetic nanoparticles. The strategy reported here can become the basis for the construction of a number of functional devices. The devices can utilize the unique recognition properties of the DNA and the magnetic properties of the nanoparticles that template them. PMID- 17722538 TI - Spatial control over cell attachment by partial solvent entrapment of poly lysine in microfluidic channels. AB - We demonstrate spatial control over cell attachment on biodegradable surfaces by flowing cell adhesive poly (D-lysine) (PDL) in a trifluoroethanol (TFE)-water mixture through microfluidic channels placed on a biodegradable poly (lactic acid)-poly (ethylene glycol) (PLA-PEG) substrate. The partial solvent mixture swells the PLA-PEG within the confines of the microfluidic channels allowing PDL to diffuse on to the surface gel layer. When excess water is flowed through the channels substituting the TFE-water mixture, the swollen PLA surface collapses, entrapping PDL polymer. Results using preosteoblast human palatal mesenchymal cells (HEPM) indicate that this new procedure can be used for facile attachment of cells in localized regions. The PEG component of the PLA-PEG copolymer prevents cells from binding to the nonpatterned regions. PMID- 17722537 TI - Geometric control of myogenic cell fate. AB - This work combines expertise in stem cell biology and bioengineering to define the system for geometric control of proliferation and differentiation of myogenic progenitor cells. We have created an artificial niche of myogenic progenitor cells, namely, modified extracellular matrix (ECM) substrates with spatially embedded growth or differentiation factors (GF, DF) that predictably direct muscle cell fate in a geometric pattern. Embedded GF and DF signal progenitor cells from specifically defined areas on the ECM successfully competed against culture media for myogenic cell fate determination at a clearly defined boundary. Differentiation of myoblasts into myotubes is induced in growth-promoting medium, myotube formation is delayed in differentiation-promoting medium, and myogenic cells, at different stages of proliferation and differentiation, can be induced to coexist adjacently in identical culture media. This method can be used to identify molecular interactions between cells in different stages of myogenic differentiation, which are likely to be important determinants of tissue repair. The designed ECM niches can be further developed into a vehicle for transplantation of myogenic progenitor cells maintaining their regenerative potential. Additionally, this work may also serve as a general model to engineer synthetic cellular niches to harness the regenerative potential of organ stem cells. PMID- 17722540 TI - Glass syringes are better than plastic for preserving arterial blood gas for oxygen partial pressure determination: an explanation based on nanomaterial composition. PMID- 17722541 TI - And the award goes to... PMID- 17722542 TI - Nanoparticles in modern medicine: state of the art and future challenges. AB - Nanoparticles are materials with overall dimensions in the nanoscale, ie, under 100 nm. In recent years, these materials have emerged as important players in modem medicine, with clinical applications ranging from contrast agents in imaging to carriers for drug and gene delivery into tumors. Indeed, there are some instances where nanoparticles enable analyses and therapies that simply cannot be performed otherwise. However, nanoparticles also bring with them unique environmental and societal challenges, particularly in regard to toxicity. This review aims to highlight the major contributions of nanoparticles to modem medicine and also discuss environmental and societal aspects of their use. PMID- 17722544 TI - Layered double hydroxide nanoparticles as cellular delivery vectors of supercoiled plasmid DNA. AB - We prepared stable homogeneous suspensions with layered double hydroxide (LDH) nanoparticles for in vitro gene delivery tests. The viability of HEK 293T cells in the presence of LDH nanoparticles at different concentrations was investigated. This revealed 50% cell viability at 500 microg/mL of LDH nanoparticles that is much higher than 50-100 microg/mL used for the delivery tests. The supercoiled pEF-eGFP plasmid (ca. 6100 base pairs) was mixed with LDH nanoparticle suspensions for anion exchange at a weight ratio of DNA/LDH between 1:25 and 1:100. In vitro experiments show that GFP expression in HEK 293T cells starts in the first day, reaches the maximum levels by the second day and continues in the third day. The GFP expression generally increases with the increase in DNA loading in DNA-LDH nanohybrids. However, the delivery efficiency with LDH nanoparticles as the agent is low. For example, the relative efficiency is 7%-15% of that of the commercial agent FuGENE 6. Three to 6% of total cells expressed GFP in an amount detectable by the FACS cytometry 2 days after transfection at 1 microg/mL of plasmid DNA with 25 microg/mL of LDH nanomaterial. The lower delivery efficiency could be attributed to the aggregation of LDH nanoparticles caused by the long-chain plasmid DNA. PMID- 17722545 TI - Glutaric acid as a spacer facilitates improved intracellular uptake of LHRH-SPION into human breast cancer cells. AB - Superparamagnetic iron oxide nanoparticles (SPIONs) bound directly to luteinizing hormone releasing hormone (LHRH) have shown high efficiency for intracellular uptake to breast cancer cells, MDA-MB-435S.luc. We demonstrate in this communication that inclusion of a small spacer molecule such as glutaric acid (Glu) in between SPION and LHRH increases further receptor mediated intracellular uptake. LHRH-bound SPIONs with and without the spacer molecule were nontoxic. PMID- 17722546 TI - Cell classification by moments and continuous wavelet transform methods. AB - Image processing techniques are bringing new insights to biomedical research. The automatic recognition and classification of biomedical objects can enhance work efficiency while identifying new inter-relationships among biological features. In this work, a simple rule-based decision tree classifier is developed to classify typical features of mixed cell types investigated by atomic force microscopy (AFM). A combination of continuous wavelet transform (CWT) and moment based features are extracted from the AFM data to represent that shape information of different cellular objects at multiple resolution levels. The features are shown to be invariant under operations of translation, rotation, and scaling. The features are then used in a simple rule-based classifier to discriminate between anucleate versus nucleate cell types or to distinguish cells from a fibrous environment such as a tissue scaffold or stint. Since each feature has clear physical meaning, the decision rule of this tree classifier is simple, which makes it very suitable for online processing. Experimental results on AFM data confirm that the performance of this classifier is robust and reliable. PMID- 17722547 TI - RGD targeted poly(L-glutamic acid)-cystamine-(Gd-DO3A) conjugate for detecting angiogenesis biomarker alpha(v) beta3 integrin with MRT, mapping. AB - Cyclic Arg-Gly-Asp-D-Phe-Lys [c(RGDfK)] targeted poly(L-glutamic acid) (PGA)-(Gd DO3A) conjugate with a biodegradable cystamine spacer was prepared and evaluated for in vivo detection of an angiogenesis biomarker, alpha(v)beta3 integrin, in neoplastic tissues with T1 mapping, a quantitative magnetic resonance imaging (MRI) technique. The binding activity of the c(RGDfK) containing conjugate was investigated using in vitro vitronectin assay with human prostate carcinoma DU145 cell line and Kaposi's sarcoma SLK cell line. The peptide c(RGDfK) and PGA cystamine-(Gd-DO3A) conjugate were used as controls. The binding affinity of polymer bound c(RGDfK) was slightly lower than free c(RGDfK) peptide. The RGD targeted conjugate had higher binding affinity to the DU145 cells than the SLK cells, which was consistent to free c(RGDfK). The imaging of alpha(v)beta3 integrin with targeted PGA-cystamine-(Gd-DO3A) was evaluated in nude mice bearing DU145 and SLK xenografts at a dose of 5 micromol-Gd/kg. The targeted conjugate demonstrated higher in vivo binding affinity to the DU145 xenografts than the SLK xenografts, resulting in a significant decrease of T1 values of water protons in the periphery of the DU145 tumors as shown in the MR T1 maps. No significant decrease of T1 values was observed in the SLK tumor with the targeted conjugate and in both tumors with the non-targeted conjugate. The targeted polymeric Gd(III) chelate conjugate with a degradable spacer has the potential to be a new paradigm for safe and effective probes in molecular imaging with quantitative MR T1 mapping. PMID- 17722543 TI - Nanoparticulate carriers for the treatment of coronary restenosis. AB - The current treatment for coronary restenosis following balloon angioplasty involves the use of a mechanical or a drug-eluting stent. Despite the high usage of commercially-available drug-eluting stents in the cardiac field, there are a number of limitations. This review will present the background ofrestenosis, go briefly into the molecular and cellular mechanisms of restenosis, the use of mechanical stents in coronary restenosis, and will provide an overview of the drugs and genes tested to treat restenosis. The primary focus of this article is to present a comprehensive overview on the use of nanoparticulate delivery systems in the treatment of restenosis both in-vitro and in-vivo. Nanocarriers have been tested in a variety of animal models and in human clinical trials with favorable results. Polymer-based nanoparticles, liposomes, and micelles will be discussed, in addition to the findings presented in the field of cardiovascular drug targeting. Nanocarrier-based delivery presents a viable alternative to the current stent based therapies. PMID- 17722548 TI - Fibroblast response is enhanced by poly(L-lactic acid) nanotopography edge density and proximity. AB - The development of scaffolds for use in tissue engineering applications requires careful choice of macroscale properties, such as mechanical characteristics, porosity and biodegradation. The micro- and nano-scale properties of the scaffold surface are also an important design criterion as these influence cell adhesion, proliferation, and differentiation. The cellular response is known to be affected by surface topography but the mechanisms governing this remain unclear. Homogenous poly(L-lactic acid) was textured with surface nanotopographies by two stage replication molding of heterogeneous demixed polymer films. Initial cell adhesion was improved on nanotextured surfaces compared with smooth controls, but subsequent cell density was significantly reduced on the roughest surfaces. Improvements in cell response were found to correlate with focal contact and actin microfilament development. Cell response was found to trend both with the surface density of topography edges and with inter-topography spacing, indicating possible roles for edges stimulating cell adhesion/proliferation or for spacing to modulate the ability of integrin-ligand bonds to cluster and form focal adhesions. This study furthers understanding of the geometric properties of surface nanotopographies that affect cellular response. It is hoped that identification of the mechanisms governing cell-topography interactions will allow rule-based design of biomaterial surface to engineer specific cellular responses. PMID- 17722549 TI - Sustained release of acyclovir from nano-liposomes and nano-niosomes: an in vitro study. AB - The present study was designed to develop and compare acyclovir containing nano vesicular liposomes and niosomes based on cholesterol, soya L-alpha-lecithin and nonionic surfactant, span 20. The effort was made to study in vitro whether acyclovir-loaded nanovesicles could sustain the release of the drug by increasing residence time and thus, acyclovir could reduce its dose-related systemic toxicity. There were good vesicular distributions in both of the niosomes and the liposomes. The obtained vesicles were within 1 microm and about 35% of them were within a size of 100 nm. The percentage of drug loading varied and the niosomal vesicles contained more drug as compared with the liposomes. When the in vitro drug release was compared, it was found that the liposomes released about 90% drug in 150 min whereas the drug release was just 50% from the niosomal vesicles in 200 min. Again, the niosomes showed better stability compared with the liposomes. Thus, niosome could be a better choice for intravenous delivery of acyclovir. PMID- 17722551 TI - Lead sulfide near-infrared quantum dot bioconjugates for targeted molecular imaging. AB - In this paper, we report the use of lead sulfide quantum dot (PbS QD) bioconjugates as near infrared (NIR) contrast agents for targeted molecular imaging with expanded emission wavelengths beyond 1000 nm. The red-shifted emission band, coupled with the small particle size, which will facilitate clearance, both afford PbS QDs unique properties for noninvasive, high resolution in vivo NIR imaging applications. We have performed imaging experiments at the molecular level using surface-modified PbS NIR QDs, together with our lab-built NIR imaging system. This novel instrumentation and fluorescent contrast agent have enabled us to study the relatively unexplored NIR biomedical imaging spectral region of 900-1200 nm. Preliminary experimental results indicate that PbS-QD/antibody bioconjugates are promising candidates for targeted NIR molecular imaging and future in vivo NIR tissue imaging applications. PMID- 17722550 TI - Quantum dot-doped silica nanoparticles as probes for targeting of T-lymphocytes. AB - To enhance diagnostic or therapeutic efficacy, novel nanomaterials must be engineered to function in biologically relevant environments, be visible by conventional fluorescent microscopy, and have multivalent loading capacity for easy detection or effective drug delivery. Here we report the fabrication of silica nanoparticles doped with quantum dots and superficially functionalized with amino and phosphonate groups. The amino groups were acylated with a water soluble biotin-labeling reagent. The biotinylated nanoparticles were subsequently decorated with neutravidin by exploiting the strong affinity between neutravidin and biotin. The resultant neutravidin-decorated fluorescent silica nanoparticles stably dispersed under physiological conditions, were visible by conventional optical and confocal fluorescent microscopy, and could be further functionalized with macromolecules, nucleic acids, and polymers. We also coated the surface of the nanoparticles with biotinylated mouse anti-human CD3 (alphaCD3). The resultant fluorescent nanoassembly was taken up by Jurkat T cells through receptor-mediated endocytosis and was partially released to lysosomes. Thus, quantum dot-doped silica nanoparticles decorated with neutravidin represent a potentially excellent scaffold for constructing specific intracellular nanoprobes and transporters. PMID- 17722552 TI - Intracellular degradation of microspheres based on cross-linked dextran hydrogels or amphiphilic block copolymers: a comparative raman microscopy study. AB - Micro- and nanospheres composed of biodegradable polymers show promise as versatile devices for the controlled delivery of biopharmaceuticals. Whereas important properties such as drug release profiles, biocompatibility, and (bio)degradability have been determined for many types of biodegradable particles, information about particle degradation inside phagocytic cells is usually lacking. Here, we report the use of confocal Raman microscopy to obtain chemical information about cross-linked dextran hydrogel microspheres and amphiphilic poly(ethylene glycol)-terephthalate/poly(butylene terephthalate) (PEGT/PBT) microspheres inside RAW 264.7 macrophage phagosomes. Using quantitative Raman microspectroscopy, we show that the dextran concentration inside phagocytosed dextran microspheres decreases with cell incubation time. In contrast to dextran microspheres, we did not observe PEGT/PBT microsphere degradation after 1 week of internalization by macrophages, confirming previous studies showing that dextran microsphere degradation proceeds faster than PEGT/PBT degradation. Raman microscopy further showed the conversion of macrophages to lipid-laden foam cells upon prolonged incubation with both types of microspheres, suggesting that a cellular inflammatory response is induced by these biomaterials in cell culture. Our results exemplify the power of Raman microscopy to characterize microsphere degradation in cells and offer exciting prospects for this technique as a noninvasive, label-free optical tool in biomaterials histology and tissue engineering. PMID- 17722553 TI - Characterization of electrospun nanocomposite scaffolds and biocompatibility with adipose-derived human mesenchymal stem cells. AB - Electrospun nanocomposite scaffolds were fabricated by encapsulating multi-walled carbon nanotubes (MWNT) in poly (lactic acid) (PLA) nanofibers. Scanning electron microscopy (SEM) confirmed the fabrication of nanofibers, and transmission electron microscopy identified the alignment and dispersion of MWNT along the axis of the fibers. Tensile testing showed an increase in the tensile modulus for a MWNT loading of 0.25 wt% compared with electrospun nanofibrous mats without MWNT reinforcement. Conductivity measurements indicated that the confined geometry of the fibrous system requires only minute doping to obtain significant enhancements at 0.32 wt%. Adipose-derived human mesenchymal stem cells (hMSCs) were seeded on electrospun scaffolds containing 1 wt% MWNT and 0 wt% MWNT, to determine the efficacy of the scaffolds for cell growth, and the effect of MWNT on hMSC viability and proliferation over two weeks in culture. Staining for live and dead cells and DNA quantification indicated that the hMSCs were alive and proliferating through day 14. SEM images of hMSCs at 14 days showed morphological differences, with hMSCs on PLA well spread and hMSCs on PLA with 1% MWNT closely packed and longitudinally aligned. PMID- 17722556 TI - Nurse united. PMID- 17722555 TI - In support of unions. PMID- 17722557 TI - Howard's way...hurting nurses? PMID- 17722554 TI - Increased nanoparticle penetration in collagenase-treated multicellular spheroids. AB - The extracellular matrix of solid tumors presents a transport barrier that restricts nanoparticle penetration, thereby limiting the efficacy of nano-sized delivery vehicles for cancer imaging and therapy. In this study, the effect of nanoparticle size and collagenase treatment on penetration of carboxylated polystyrene nanoparticles was systematically assessed in a multicellular spheroid model. Penetration of the nanoparticles into the spheroid core was limited to particles smaller than 100 nm. Collagenase treatment of spheroids resulted in significantly increased penetration of nanoparticles up to 100 nm with only a minor increase in particle penetration observed for particles larger than 100 nm. Collagenase was immobilized onto the surface of nanoparticles for site-specific degradation of ECM proteins. Collagenase-coated, 100 nm nanoparticles demonstrated a 4-fold increase in the number of particles delivered to the spheroid core compared with control nanoparticles. Thus, nanoparticle delivery to solid tumors may be substantially improved by the incorporation of ECM-modulating enzymes in the delivery formulation. PMID- 17722558 TI - Nursing guidelines for assessment and management of urinary retention in hospitalised older adults. PMID- 17722559 TI - Educational interventions for mental health consumers receiving psychotropic medication. PMID- 17722560 TI - Working life: a journey of a lifetime. PMID- 17722561 TI - Understanding transition in chronic illness. PMID- 17722562 TI - Point of care INR testing in cardiac wards. PMID- 17722563 TI - Help is just a phone call away. PMID- 17722564 TI - Managing medications and chronic illness. PMID- 17722565 TI - [Using stromal stem cells for the periodontal tissue regeneration and their interaction with tissue microenvironment]. AB - This review paper describes the evolution of the ideas of periodontal tissue regeneration, starting with the concept of selective cellular repopulation, stimulation of resident precursor cells in the regeneration focus, up to the application of versatile potential of the stromal stem cells (SSC). Effects of stem cells isolated from an embryo, bone marrow, and adipose tissue, are described, as well as the immunophenotype of freshly isolated SSC, that of precultured vascular cell fraction as compared with the immunophenotype of SSC cultured during various time periods. The results of the study of the processes of proliferation and cell differentiation of SSC transplanted into the deep periodontal defects, are analyzed using proliferating cell nuclear antigen (PCNA) and green fluorescent protein. During the process of regeneration, the interaction of transplanted SSC with the local microenvironment is mediated by special membranous cell receptors. The coordination of cell behavior by means of adhesive and communicative contacts which provide a signal platform for the control of cellular functions, is discussed. PMID- 17722566 TI - [Structural organization of the zona incerta in the dog diencephalon]. AB - Zona incerta in dog diencephalon was studied by the methods of Nissl and Kluver Barrera. As a result of this study, 5 individual sectors were identified on the basis of the analysis of fiber Organization, morphological types of neurons and the density of their distribution. The mapping of zona incerta was performed, and the borders of the sectors were accurately determined by histochemical demonstration of NADPH-diaphorase-positive neurons. PMID- 17722568 TI - [Topographic-anatomical aspects of nerve-saving operations in the temporal area and in the lateral part of a face]. AB - Bicoronary access is now considered as optimal for performance of operative interventions in the upper part of face. At the same time, this access is associated with the probability of damaging the innervation of the frontal muscles. Thus, the objective of this investigation was to study the individual variability of topography of facial nerve branches in temporal and parotid areas, with specification of projections of temporal branches of a facial nerve to frontal muscle in order to define a safe zone for dissection. The material was obtained from 36 corpses of adult persons, and precision preparation method was used together with the recording and mathematical processing of the results obtained. It was established, that in objects with a size of tragoorbital line less than 8 cm, a single frontal branch of a facial nerve was present, and its safety zone was about 1 cm to the front from tragus auris. In objects with the size of tragoorbital line equal to 8 cm and more, a common trunk of frontal branch of facial nerve was present together with a branch to m. orbicularis oculi, while its safety zone was equal to 1.5 cm and it was located to the front of tragus auris. PMID- 17722569 TI - [The dynamics of reparative regeneration of the rat skin nerve after various degree of its damage]. AB - The dynamics of skin nerve regeneration was studied during 10-50 days after it was damaged by crushing in 163 outbred rats. Two series of experiments were conducted. In the first series, skin nerve (n. saphenus) was crushed by a hemostatic clamp in a region 2 mm long, while in second series it was crushed in a region of 4 mm length. The destructive processes in LIII and LIV spinal ganglia, the increase in the number of myelinated nerve fibers in the nerve region distal to the damaged area, the velocities of growth of damaged nerve fibers to the skin, were similar in both series during 10-50 days after the nerve was injured at different length. The velocity of myelination of regenerating nerve fibers in rats after 2 mm-long nerve injury was higher than that in animals after 4 mm-long nerve injury for a period of 30 days after the damage. PMID- 17722567 TI - [Age-dependent peculiarities of apoptotic marker proteins expression in the neuroendocrine system of Her2/neu transgenic mice]. AB - The aim of our work was to study the expression of apoptotic signaling proteins and its relation to apoptosis level in neuroendocrine system of HER2/neu transgenic mice in aging. SHR mice served as controls. Bcl-2, Mcl-1, p53 and caspase-8 were demonstrated by immunohistochemistry in supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei and relative content of apoptotic neurosecretory cells was determined. It was demonstrated that apoptosis regulation in different nuclei in old SHR mice was mediated by various signaling pathways: in SON, p53-independent cascade was activated, while in PVN it was p53 dependent. Overexpression of HER2/neu was shown to protect against the age related apoptosis activation in neurosecretory centers. HER2/neu suppressed the synthesis of proapoptotic protein p53, causing the reduction of caspase-8 expression, that resulted in the increased survival of neurosecretory cells in aging. PMID- 17722570 TI - [Efferent innervation of the cervical region of the trachea during the early postnatal ontogenesis]. AB - Method based on retrograde axonal transport of horseradish peroxidase was used to study the efferent innervation of the cervical trachea in neonatal, 10-, 20-, 30 day-old and two-month-old kittens. In all the animals, labeled neurons were localized in the cranial cervical, middle cervical and cervicothoracic (stellate) sympathetic ganglia both on the right and on the left sides. Neurons were also localized at the level of medulla oblongata, in the dorsal and ambiguus nuclei of the vagus nerve. Labeled neurons were also found in the ventral horns of C(I )C(V) spinal segments in the animals before 30 days of life. The number of sympathetic neurons, innervating the trachea, cells increased from the moment of birth, reaching a maximum by the age of 10 and 20 days and then declined up to the second month of life. The total number of parasympathetic neurons decreased gradually in the early development. PMID- 17722571 TI - [Identification of the cells expressing neural markers in normal and pathological human dental pulp]. AB - This work presents the results of a immunohistochemical study, performed in order to identify the cells in human dental pulp which express neural markers. Population of cells expressing neuron-specific enolase, synaptophysin, and chromogranin A, which were stained by paraldehyde-fuchsin, was demonstrated in subodontoblastic layer of the dental pulp. Changes the number, morphological and functional characteristics during development of caries and pulpitis in combination with periodontitis are described. PMID- 17722572 TI - [Morpho-functional characteristics of the lingual epithelium after administration of hydra peptide morphogen]. AB - Using histological, morphometric and quantitative histoenzymological methods, the changes of lingual epithelium were studied in 40 outbred albino mice after 5 intraperitoneal injections of 100 micrograms of hydra peptide morphogen (HPM) per 1 kg of body weight. Administration of HPM was found to increase the total thickness of epithelial layer on the dorsal tongue surface in the interpapillary regions, while in the area of filiform papillae these changes were not significant. On the ventral tongue surface HPM induced a marked increase of total thickness of the epithelial layer as compared to that in control animals. Mitotic activity was increased in the epithelium covering the ventral surface and in the interpapillary regions on the dorsal tongue surface. Histoenzymologic study which involved the demonstration of NADH-diaphorase, succinate- and lactate dehydrogenase (LDH) activities, followed by a cytophotometric evaluation of enzyme activity, has shown a stimulatory effect of HPM on the activity of all the enzymes studied, which was most pronounced in respect to LDH and was maximally expressed on the dorsal tongue surface. These findings collectively suggest that HPM exerts a stimulatory effect on proliferation activity and metabolism of lingual epithelium, which is differentially expressed in its variuoe topographical zones. PMID- 17722573 TI - [Structure of the metaepiphyseal growth plate cartilage in conditions of total isolation from cellular and humoral influences after its transplantation into soft tissues (an experimental study)]. AB - The aim of this study was to determine the effect of a skeletal muscle on the cartilage of growth plate of metaepiphyseal explants of tubular bones of growing and mature Chinchilla rabbits (n = 18) under conditions of their isolation from cellular and humoral influences. In experimental animals, metaepiphyseal explants of metatarsal bones, containing growth plate, were sealed in polyethylene film and were placed, under local anesthesia, in the femoral muscles. One week later these grafts were removed and studied histologically. Despite the absence of the effects of biologically active substances and immunocompetent cells of the donor (foreign) organism, the exposure of the cartilage plate to the environment of the muscular tissue lead to some typical changes in its structure. The results obtained may indicate the susceptibility of the cartilage growth plates to the action of some distant factors, probably, of an electromagnetic nature. The detection of these factors is promising for the development of clinical methods of the stimulation of the damaged cartilage growth plates for the correction of bone deformities. PMID- 17722575 TI - [Criteria for evaluation of functional importance of endogenous analogues of pharmacological regulators]. AB - Some criteria for the evaluation of the functional importance of endogenous analogues of pharmacological drugs are proposed. For endogenous regulators, these include opposite changes in their content in opposite (patho)physiological states, accompanied by corresponding changes in the functional activity of enzymes sensitive to changes in their level; regulation of target enzymes by physiological concentrations of such endogenous compounds. The applicability of these criteria has been demonstrated using tribulin, the endogenous family of inhibitors of monoamine oxidases. PMID- 17722574 TI - [Synthesis of artifical genome as the basis of synthetic biology]. AB - Recent achievements in the whole-genome sequencing especially viral and bacterial ones, together with the development of methods of bioinformatics and molecular biology, have created preconditions for transition from synthesis of genes to assembly of the whole genomes from chemically synthesized blocks, oligonucleotides. The creation of artificial genomes and artificial cells, will undoubtedly render huge influence on a deepening of knowledge of mechanisms of functioning of living systems at a cellular level, on a way of origin and evolution of life, and also on biotechnology of the future, and will generate preconditions for the further development of synthetic biology and nanobiotechnology. PMID- 17722576 TI - [Nonsteroidal anti-inflammatory drugs. Declaration I. A study of interrelation "structure--the effectiveness of anti-inflammatory action"]. AB - Using the computer system SARD-21 (Structure Activity Relationship & Design) the structural features typical for high- and low- effective nonsteroid anti inflammatory drugs (NSAIDs) were analyzed. This information has been used for the model for prediction of anti-inflammatory effectiveness of medicines with 76% and 81% level of recognition by two methods. New data can be used for creating new highly effective NSAIDs, and for increasing effectiveness of already known components. PMID- 17722577 TI - [Oxidative metabolism and crystal-forming properties of blood of the experimental animals subjected to nonsymmetrical dimethylhydrazine]. AB - We have studied parameters of oxidative metabolism and crystal-forming properties of the rat blood under conditions of intoxication by nonsymmetrical dimethylhydrazine (NDMH). We have found the increase of secondary and end products of lipid peroxidation in blood erythrocytes 7 days after NDMH injection at a dose of 5 mg/kg. Administration of a higher dose of NDMH (70 mg/kg) results in essential accumulation of initial, secondary and end-products of lipid peroxidation in rat erythrocytes, accumulation of products of protein oxidative modification in blood plasma. Studies of plasma crystal-forming properties have shown, that the increase of a dose of the injected toxicant causes the loss of ash value and symmetry in arrangement of basic elements of facies (concretions, separateness, cracks), changes of their shape or their full disappearance. There are abnormal fields (individual or plural tongue structures, "wrinkles", sheet structures, garrot-like structures etc.). Thus the bright picture of the plasma structure-forming properties is noted already at low NDMH doses. The results obtained suggest close interrelation between the impairments of physical and chemical properties of blood plasma in experimental animals under canditions of toxic action of NDMH. PMID- 17722578 TI - [Mechanisms of regulation of glycolytic enzymes in rat liver under morphine intoxication]. AB - The influence of acute morphine intoxication on glycolytic enzymes in liver has been investigated. The most significant changes were found under the action of the drug in the dose of 10 mg/kg. We also studied in vitro action of morphine in the concentrations 1, 10 and 50 microg/ml on the key glycolytic enzymes activities in rat liver. The direct dose-dependent inhibition of the glycokinase activity was shown. The changes in functional state of carbohydrate metabolism accompany hormonal imbalance in the animal bodies. PMID- 17722579 TI - [Adenylate level and lactate dehydrogenase (LDH) in the sympathetic ganglion: the effect of N-cholinergic blockade]. AB - Activity of LDH isoenzymes and the level of ATP, ADP, and AMP were determined in the rabbit superior cervical sympathetic ganglion under conditions of experimentally induced partial or total blockade of N-cholinergic (N-CE) synapses. This blockade changed the spectrum of LDH isoenzymes: partial blockade was accompanied by disappearance of LDH-4 and LDH-5; total blockade also caused disappearance of LDH-3. LDH-1 and LDH-2 that remained in the isoenzyme spectrum as well as total LDH activity decreased significantly. Under conditions of total N-CE blockade total activity of LDH represented 9% of control, whereas activity of LDH-1 and LDH-2 represented 16% of control. ATP content decreased by 53 and 93% under conditions of partial and total N-CE blockade, respectively. The levels of ADP and AMP decreased by 33 and 65 and 80 and 56%, respectively. Results of the present study suggest that activity of N-CE synapses is a crucial factor involved into the energy homeostasis of the sympathetic ganglion. PMID- 17722580 TI - [Elaboration of new adjuvant lipid-saponin complex and its use at experimental immunization by bacterial antigen]. AB - Results of experiments on modification of immunostimulating complexes (ISCOM's) matrix by the replacement of the phospholipid for the glycolipid (monogalactosyldiacylglycerol) from sea macrophytes, and saponin QuillA to triterpene glycoside of cucumarioside A2-2 from Cucumaria japonica are shown. The resultant complexes include the morphological structures of two types: ISCOM-like structures with the characteristic morphology and sizes and also the tubular structures with diameter of approximately 40 nm and length of 150-400 nm. We have named these structures as TI-complexes. These TI-complexes exhibit considerably lower toxicity than ISCOM. They may include an amphiphilic protein antigen and provide immunoadjuvant effect during experimental vaccination. Under conditions of experimental immunization of mice by a weak immunogen--(subunit membrane pore protein from Y. pseudotuberculosis), TI-complexes with antigen provided stronger humoral immune response to antigen than the complexes of porin with classical ISCOM, liposomes and Freund's adjuvant. Thus, it's shown the prospect of the use of TI-complexes as a new type of adjuvant carriers for antigens. PMID- 17722581 TI - [Changes in free amino acid contents in the liver and heart under the conditions of restricted movement activity]. AB - The contents of the free amino acid in the liver and heart tissues were investigated under conditions of experimental hypokinesia on 15th, 30th and 45th days by means of HPLC method. The content of glutamate and aspartate in the liver tissue was sharply decreased with the increase of the hypokinesia period. The degree of the decrease of aspartate was more pronounced than glutamate. The level of glycine in the liver remained unchanged on 15th and 45th days of hypokinesia but increased on the 30th day compared with control animals. There were insignificant changes in taurine content. In contrast to the liver tissue the contents of monoaminodicarbonic acids were increased in the myocardum. The content of taurine was decreased over the whole period of restricted movement activity compared with control, especially on the 15th day of hypokinesia. The changes of free amino acids are discussed in terms of their participation in energy metabolism of both tissues during the restricted movement activity. PMID- 17722582 TI - [Mechanisms of ischemic heart injury attenuation by means of a modified reperfusion]. AB - Mechanisms of attenuation of membrane injury and metabolic disturbances in postischemic cardiomyocytes have been studied on a model of ischemic and reperfusion stress of rat heart using a modified early reperfusion. Optimization of reperfusion infusate composition augmented cardiac pump and contractile function recovery. This was accompanied by a reduced release of lactate dehydrogenase activity and systems generating short-lived reactive oxygen species into myocardial effluent and was associated with more efficient oxidative metabolism recovery and decreased losses of intracellular total creatine and amino acids pools. The results indicate availability of postischemic functional and metabolic myocardial injury correction by means of a controlled reperfusion. PMID- 17722584 TI - [Chemical composition of milk of puerperas suffered from gestosis of different degree of severity]. AB - In mature breast milk of puerperas, suffered from gestosis, there was a decrease in total protein content, serum proteins (basically due to the fraction of gamma immunoglobulins), a decrease in quantity of essential amino acids, content of fats (total lipids, triglycerides, cholesterol and phospholipids), carbohydrates, basic microelements and macroelements (calcium, phosphorus), vitamins A and E in dependence of the level of severity of considered complications during pregnancy. Increased content of products of lipid peroxidation (conjugated dienes, malonic dialdehyde, Schiff bases), as well as sodium, magnesium was also detected. PMID- 17722583 TI - [Expression of interstitial collagenase and its endogenous regulators in immortalized and transformed by E7 gene HPV16 fibroblasts]. AB - Matrix metalloproteinases (MMPs) play a critical role in tumor development and invasion. The aim of this study is to elucidate peculiarity of expression of interstitial collagenase (MMP-1) and its endogenous regulators in the process of oncogenic transformation of fibroblasts by E7 gene of HPV16. Papilloma virus type 16 and 18 are aetiological factor of cervical cancer. We have studied expression of MTI-MMP, MMP-1, tissue inhibitor of these proteases TIMP-1 and urokinase typeplasminogen activator (uAP). The study was carried out using fibroblasts immortalized by LT gene (IF) and transformed by E7 gene of HPV-16 fibroblasts (TF). Primary culture of Fisher rat embryo fibroblasts was used as a control (PF). mRNA expression was studied by RT-PCR, enzymatic activity--by hydrolysis of fluorogenic type I collagen. It was found that cell transformation is accompanied by: a) 2-3 fold induction of MT1-MMP mRNA expression (vs PF); b) the decrease in mRNA level of TIMP-1 (1,5-2 fold); c) unchanged uPA expression. Cell immortalization is accompanied by: a) the increase of MT1-MMP expression (1,5-2 fold); b) unchanged TIMP-1 expression; c) the increase of uPA expression (2-4 fold) (vs PF and TF). MMP secreted activity and activity in lysates of TF increased but the level of free endogenous MMP inhibitors decreased (vs IF). Data on gene expression are consistent with enzymatic data on the collagenolytic activity. These results suggest changes in enzyme/inhibitor/activator ratio both TF and IF and significant enhancement of the destructive potential of the TF. PMID- 17722585 TI - [Parameters of plasma blood proteolysis and phenotypes of alpha1-proteinase inhibitor in children with duodenal ulcer]. AB - The aim of this study was to determine correlation between proteolysis parameters and phenotypes of alpha1-proteinase inhibitor in blood plasma in children with duodenal ulcer. Activation of pepsin- and trypsin like proteinases was accompanied by the decrease in activity of alpha2-macroglobulin and the increase in activity of acid stable inhibitors. The phenotypes M1M3, M1M1, M2M2 of alpha1 proteinase inhibitor were determined. Activation of proteolysis was more pronounced in individuals with subtype M2M2. Activity of alpha1-proteinase inhibitor decreased by 2-fold in M2M2, insignifically differed from the control group in M1M1, and increased by 1,9-fold in M1M3 subtype. Low activity of alpha1 proteinase inhibitor was accompanied by high activity of acid stable inhibitors; this may be regarded as the protective reaction of the body. Determination of alpha1-proteinase inhibitor phenotypes may be a basis for employment of polyvalent proteinase inhibitors for therapy of ulcer. PMID- 17722586 TI - [Regenerative and plastic heart failure: molecular biological mechanisms and morphological bases]. AB - Regenerative and plastic heart failure resulted in impaired or inhibited biosynthetic processes (plastic metabolism) and hence decreased or ceased intracellular cardiomyocytic regeneration. Atrophic (involutional) processes of cardiomyocytes and their progressive deficiency due to apoptotic death (diffuse cardiomyocytic depopulation), accompanied by the development of diffuse cardiosclerosis play the key role in regenerative and plastic heart failure. Diffuse myocardial sclerosis may be regarded as a corrected compensatory connective tissue response to a pronounced decrease in muscle fiber mass. In anthracycline-induced cardiomyopathy, myocardial remodeling as a result of changes in the pattern of parenchymal and stromal interactions occurs in the dilatation mode and induces no severe cardiac deformation, which is a favorable factor in restoring the normal myocardial architectonics when regenerative processes are resumed. PMID- 17722588 TI - [Diagnosis of lymphoproliferative diseases by bone marrow trepanobiopsy specimens]. AB - Based on the study of 2000 bone marrow trepanobiopsy specimens from patients with different types of lymphoproliferative diseases, the authors present the incidence and specific features of specific bone marrow lesion and the state of normal hemopoiesis and stroma. They also give data of bone marrow immunohistochemical studies using a many mono- and polyclonal antibody panels. The criteria for the differential diagnosis of reactive polyclonal lymphoid proliferation in the bone marrow that may accompany many hematological and non hematological diseases with specific bone marrow lesion in lymphoproliferative diseases are outlined. The high diagnostic value of a study of bone marrow trepanobiopsy specimens is shown in the diagnosis of lymphoproliferative diseases. PMID- 17722587 TI - [Immunomorphological study of angiotensin-converting enzyme in coronary shunts]. AB - Coronary bypass surgery is the operation of choice in patients with coronary atherosclerosis. However, some time later, venous shunts frequently stop functioning after successful surgery. The reasons for this include intimal hyperplasia occurring in response to release of cytokines, angiotensin II in particular. In man, the latter is formed by angiotensin-converting enzyme or chimase. The findings show that elevated ATF concentrations are found in some cells in the area of intimal hyperplasia, in macrophages and smooth muscle cells of the shunt hyperplastic intima. The increased ATF concentration in the aorto coronary shunt cells results in the elevated levels of angiotensin II, the migration of smooth muscle cells, their hypertrophy and hyperplasia, the formation of atherosclerotic plaques, thrombosis, and circulatory disorders. PMID- 17722589 TI - [Low-grade fibromyxoid sarcoma: analysis of 8 cases]. AB - The diagnosis of low-grade fibromyxoid sarcoma was made in 8 patients. The lesions were 2-17 cm in the lower extremities and trunk. One patient had a long history of painless subcutaneous and intramuscular mass (median 1 year). All tumors showed predominantly the typical hypocellularity and cytologic features of typical low-grade fibromyxoid sarcoma; however, the areas of hypercellularity and nuclear enlargement and hyperchromatism were identified. No necrosis and mitotic activity less than 2 mf/50 HPF were present. Ultrastructurally, the tumor composed of neoplastic fibroblasts. No other cell differentiation was identified. Immunohistochemically, the neoplastic cells showed a positive response to vimentin and fibroblast antigen; no muscle-specific antigens were revealed. The Ki-67 labeling index with MIB-1 ranged 2-6%. PMID- 17722590 TI - [The proapoptotic factor HLDF in the normal, hyperplastic and neoplastic endometrium]. AB - Antibodies to the factor HLDF are shown to be specific markers of apoptosis and permit the estimation of the rate of programmed cell death in the course of a normal menstrual cycle and in pathologic endometrial processes. HLDF expression in the epitheliocytic cytoplasm makes it possible to evaluate apoptosis at early stages, before the emergence of the first morphological signs and after apoptotic body formation. The study shows increased apoptotic processes at the end of a normal menstrual cycle and during neoplastic cell transformation. Antibodies to the HLDF factor may be used as a new immunohistochemical marker for the differential diagnosis of benign and malignant endometrial processes. PMID- 17722591 TI - [Pathomorphological changes in the lung in tuberculosis patients died from HIV infection at the stage of AIDS]. AB - The authors revealed the typical morphological changes of lung tuberculous lesion in HIV infection at the stage of AIDS: these included alterative changes without typical tuberculosis granulomas; a well-defined exsudative inflammatory component with a predominance of leukocytic infiltration and a drastically decrease of and, occasionally, a complete disappearance of macrophages and lymphocytes; formation of pyonecrotic foci; the focal monomorphic pattern illustrating the loss of the signs of process indulation. These signs suggest the specific features of immunity and the course of specific inflammation as immediate hypersensitivity with the acutest progression of tuberculosis. PMID- 17722592 TI - [Role of matrix metalloproteinases in the pathogenesis and morphogenesis of fibrocavernous tuberculosis in persons long living in the Semipalatinsk region of Kazakhstan]. AB - The archives of surgical material (removed lungs and their parts) and autopsies of 54 patients with fibrocavernous tuberculosis (FCT) who had lived from childhood to 2003 near polluted area and exposed to radiation (the annual radiation dose was higher than 0.1 Rem) were studied. The surgical and autoptic materials from 21 patients with tuberculosis (including 6 patients lived in the Kazakhstan radiation areas and 15 patients lived in Moscow) were used as a control. The morphological features of FCT in the persons who had long lived in the radioactively polluted areas were marked lung destructive and fibrotic changes, a decrease in the detection rate ofgranulomatous inflammation, and a weak local lymphoid infiltration, which may indirectly suggest the low level of cellular immunity upon exposure to ionizing radiation. PMID- 17722593 TI - [Characteristics of perinatal visceral lesions caused by chlamydia trachomatis]. AB - Twenty-three autoptic cases of perinatal chlamydiasis were analyzed. Its etiology was verified by immunofluorescence technique using monoclonal antibodies. The morphological characteristics of visceral lesions are given. Data on the possible routes of infection and evidence for the development of generalized chlamydiasis are presented. The kidney may be suggested to be the site of pathogen persistence. PMID- 17722594 TI - [Causes of deaths in patients with injuries]. AB - The causes of death were analyzed in patients with injuries treated at City Clinic No. 31 in 2004-2005. Over this period, 83 patients died, 64 of them underwent forensic medical examination, 17 were autopsied; 2 cases were not. The underlying and immediate causes of death are described in relation to the type of injury. PMID- 17722595 TI - [Wegener's granulomatosis: manifestations of skin lesions]. AB - 16 fatal cases of Wegener's granulomatosis (WG) were morphologically and histochemically studied. In all cases various changes were found, which generally correlated with the severity of the disease, depending on its course and complications and were responsible for the progression of the disease and deteriorated its prognosis. The morphological criterion of WG was destructive productive angiitis mainly of the microcirculatory bed, with the development of disseminated intravascular coagulation (DIC), and the formation of peri- and endovascularly specific, highly polymorphic granulation tissue, followed by its necrosis. DIC supplemented by infection resulted in impairment of trophism, hypo- and anoxia of tissue and, further all skin morphofunctional structures. PMID- 17722597 TI - [Gastric tumor of complex structure]. AB - The paper describes a case of gastric tumor comprising moderately differentiated adenocarcinoma and atypical carcinoid with metastases of both types of tumor cells in the lymph nodes. Electron microscopic and immunohistochemical studies of primary gastric tumor and lymph nodal metastases confirmed the presence of both differentiation types within one space-occupying lesion: such as goblet (mucin producing) and neuroendocrine cells. The differentiation varied in different fields of vision with a preponderance of low-grade ultrastructural differentiation cells. Thus, electron microscopic and immunohistochemical studies of tumors not only verify their diagnosis and make a histogenetic differential diagnosis of various neoplasms, but also define the degree of their maturation. PMID- 17722596 TI - [Pathomorphological features of placentas with the single umbilical artery and a study of follow-ups of these babies]. AB - The paper deals with the evaluation of pathomorphological and morphometrical changes in placenta with the single umbilical artery (SUA). The histological data on 52 placentas with SUA (group 1) were analyzed. A control group included 30 placentas from females with an uncomplicated obstetrical history. The significance of group differences was determined Student's test. In the placentas with SUA, their pathohistology shows a significantly marked isolated placental form of chronic placental insufficiency. In SUA, chorionic villous maturation and differentiation are impaired. Chorionic villous immaturity hampers the development of adequate compensatory adaptive changes that appear as compensatory angiomatosis of terminal villi and more pronounced cytotrophoblastic microcystic changes. PMID- 17722599 TI - [Primary lung osteosarcoma simulating gastric carcinoma]. AB - The rarest case of primary lung osteosarcoma is described. Despite the fact that an extended clinicoinstrumental study was conducted, the clinicians who interpreted the process to be a destructive gastric carcinoma did not diagnose the site of the tumor. Autopsy identified the unusual form of primary lung malignancy progression with an advanced invasion into the organs on both sides of the diaphragm, including the gastric wall. PMID- 17722598 TI - [Gastrointestinal stromal tumor of the stomach, concurrent with pancreatic adenocarcinoma]. AB - The paper presents the data available in the literature and the authors' own data on a concomitance gastrointestinal tumor of the stomach and cancer of the pancreas head, which developed in a 56-year-old patient. A morphological (histological and immunohistochemical) study has established the spindle-cell type of a gastrointestinal tumor that expresses Vimentin, as well as CD 34, CD 117, and pancreatic ductal adenocarcinoma. PMID- 17722600 TI - [Idiopathic esophageal enlargement in a 68-year-old male]. AB - The authors describe a rare case of undiagnosed lifetime malformation of the esophagus as its idiopathic enlargement undiagnosed in a 68-year-old male. The size of the organ was 10 to 20 cm in diameter and up to 25 cm in length. The esophageal mucosa was covered with the papillomatously changed laminated squamous epithelium with chronic inflammation in the mucous stroma. The case is of certain clinical and pathomorphological interest due to its rarity of undiagnosed lifetime malformation. PMID- 17722601 TI - [Chondroblastoma]. AB - Chondroblastom, benign cartilage tissue neoplasm, accounts for 1% of all bone tumors. It is encountered in any skeletal bones mainly in persons aged 10 and 25 years. Morphologically, it is represented as large homogenous cells--well-defined oval polygonal chondroblasts with a fine eosinophilic cytoplasm, and a round-to oval nucleus. Cartilaginous portions of chondroblastoma form lobular structures. The tumor always comprises single-to-multiple multinucleate giant cells. The pathognomonic sign of chondroblastoma is intercellular reticular basophilically stained calcifications as a mesh. Mitotic cells, rather than abnormal ones, are present. There are cases of primary malignant chondroblastomas. PMID- 17722602 TI - [Molecular biological aspects of the pathogenesis of adenomyosis]. AB - The review of literature concerns some aspects of the pathogenesis of adenomyosis in terms of occurring molecular biological processes. It pools the literature data on endometrial capacity to be plunged into the deep myometrial layers--the expression of adhesive molecules, endometrial proteolytic activity, angiogenetic factors, and apoptosis-proliferation relationships. Evidence for the metaplastic theory of the disease is also presented. Emphasis is laid on the characteristics of a subendometrial zone whose pathology plays an important role in adenomyosis. PMID- 17722603 TI - [Effect of viruses on the host cytokine system]. AB - The review considers recent data on the mechanism of action of viruses on the host cytokine system. The inhibitory and stimulant effects of viruses and their antigens on the production of cytokines, interferons in particular, are described. Examples of the behavior of specific viruses are given. Particular emphasis is laid on the viruses of the Herpesvididae family. The role of cytokine gene polymorphism in the pathogenesis is discussed. PMID- 17722604 TI - [Comparative analysis of hepatitis C virus core protein in the plasma and serum samples from HCV-infected blood donors and patients with hepatitis C]. AB - The aim of the study was to develop a sensitive and specific method for revealing the direct marker of hepatitis C virus (HCV)--core protein in the serum and to test it in the laboratory setting. Experiments were made on plasma and serum samples from asymptomatic HCV-seropositive blood donors (n=65), patients with acute (AHC) and chronic (CHC) hepatitis C (n=295), and HCV-seronegative blood donors (n=20). The processing protocol for serum included their concentration by means of polyethylene glycol and subsequent treatments of pellets to detect core protein in free virions, nonenveloped nucleocapsids, and immune complexes. This allowed an assay to be developed for the detection of core protein, by using a sandwich ELISA. Inclusion of a combination of three original monoclonal antibodies into the sandwich could reveal in the samples core proteins of at least 3 genotypes of HCV (1, 2, and 3) with a sensitivity of 20 pg/ml in the majority of HCV-infected subjects. The results of determination of core protein and HCV RNA correlated with a high degree of sensitivity. To detect HCV in the blood of patients with AHC, it was shown to be sufficient to find freely circulating virions whereas an analysis of immune complexes should be included in cases of CHC to achieve more sensitivity. The findings are a basis for developing a test system for the diagnosis of hepatitis C, including its early stages before seroconversion and for determining a viral load during interferon therapy. Introduction of the method into practice increases the reliability of the diagnosis of hepatitis C and virus-free safety of blood transfusions. PMID- 17722605 TI - [Development of polymerase chain reaction-based test systems for influenza A virus isolation and typing]. AB - Influenza viruses are spread worldwide and cause the disease in birds and mammals, including human beings. Moreover, birds are the natural reservoir of influenza A viruses. Early detection of newly emerging influenza viruses requires permanent monitoring. Traditional viral shedding methods using cell cultures and chicken embryos are time-consuming and laborious analysis when a large number of samples are examined. The paper describes the use of polymerase chain reaction based test systems to detect influenza A virus and to differentiate its two subtypes: H5 and H7. The developed test systems were evaluated on 19 reference influenza A virus strains. Thereafter, more than 1500 samples from wild and domestic birds, collected in the Russian Federation in 2004-2006, were studied. The data of these test systems were compared with the techniques of viral shedding in the cell cultures and chicken embryos. PMID- 17722606 TI - [Live influenza vaccine: laboratory markers of attenuation]. AB - Screening for candidate reassortants is an important step in the development of live influenza vaccine (LIV). The temperature-sensitive (ts) and cold-adapted (ca) phenotypes of vaccine strains are generally determined, by employing chicken embryos, and used as ts and ca attenuation markers. However, it is difficult to use the egg-determined ts phenotypes of vaccine candidate reassortants as an attenuation marker due to a wide circulation of natural ts epidemic influenza viruses. This study used two new alternative ts and ca attenuation markers in MDCK cells. The MDCK cell line was shown to be able to differentiate cold-adapted influenza viruses from any epidemic strains whereas they were undistinguishable when using eggs. The reduced ability of influenza type A vaccine viruses to grow in the MDCK cell culture at temperatures above 37 degrees C can be successfully used as a "cell-culture" ts marker. The similar marker for influenza B viruses may serve their reduced activity in the MDCK cells at 38 degrees C. The high reproductive activity of cold-adapted viruses in the MDCK cells at 26 degrees C was shown to be a suitable ca attenuation marker. The presented attenuation markers may be included into the standard scheme of primary screening of ts reassortant candidates for commercial live influenza vaccine as additional selection factors and may be used as basic markers in the design of culture vaccine. PMID- 17722607 TI - [The inoculative properties of cold-adapted reassortant A(H5N2) influenza strain during intranasal administration to mice]. AB - Classical genetic reassortant techniques were used to have a cold-adapted (ca) reassortant A/17/Duck/Potsdam/86/92 (H5N2) that inherited the hemagglutinin (HA) gene from the nonpathogenic avian virus A/Duck/Potsdam/ 1402-6186 (H5N2) and the genes of neuraminidase (NA) and non-glycated proteins from the ca attenuation donor A/Leningrad/134/17/57 (H2N2). All experiments were performed under increased biological protection (BSV-3+). The reassortant and parent H5N2 virus were non-pathogenic to Balb/c mice, the reassortant replication in the murine nasal passages (3.5 Ig EID50/ml) being higher than that in the lung (2.1 lg EID50/ml). Intranasal inoculation of mice with reassortant A/17/Duck/Potsdam/86/92 caused an immune response to both homological H5N2 virus and antigenically differing variants of influenza A (H5N1) virus isolated from humans in 1997 and 2003. The mice intranasally immunized with the ca reassortant were protected against fatal infection with the highly pathogenic A/Hong Kong/483/9797 (H5N1) virus and against infection with A/Hong Kong/213/03(H5N1) virus (80 and 100%, respectively). PMID- 17722608 TI - [The morphofunctional state of the blood-brain barrier at the level of the medulla oblongata in experimental West Nile encephalitis]. AB - Pronounced clinical and morphological changes were found in the neurons and microcirculatory bed (MCB) vessels at the level of the medulla oblongata in experimental West Nile encephalitis (WNE). At the same time, the magnitude of changes in MCB vessels and nerve cells in the cores of the medulla oblongata correlated with the state of the surrounding astrocytic glia. It is suggested that the intensive astroglial reaction revealed during this experimental WNE reproduction promotes the prevention of neuronal lesion. PMID- 17722609 TI - [The in vitro antiviral activity against the causative agent of hemorrhagic fever with renal syndrome]. AB - It is shown that primary screening of drugs against the pathogens of hemorrhagic fever with renal syndrome (HFV) may be performed, by using two approaches in estimating the suppression of plague formation and that of viral reproduction in the cultured cells. It is expedient to make a primary screening of interferon and its inductors to estimate the suppression of viral reproduction in the cultured Vero E6, PSEV, and CL-17 cells, the infection multiplicity should be hundredth parts of BOE/cell. Among the test agents, there are virazole and realdiron that are the most active drugs against Hantaan virus, 76-118 strain, which virually completely suppress the reproduction of the study causative agent, when used even at concentrations of 1-5 microg/ml and 100 U/ml, respectively. PMID- 17722610 TI - [Bovine coronavirus reproduction in the continuous cell cultures at a temperature of 34 degrees C]. AB - Cultivation of bovine coronavirus at 34 degrees C showed the relationship of the degree of its reproduction to the cellular system. The possibility of obtaining the double yield of bovine coronavirus was demonstrated in MDBK and Vero cell cultures at 34 degrees C. PMID- 17722611 TI - [Pathogenesis of mixed experimental infection caused by diarrheal viruses--bovine mucosal disease and bovine infectious rhinotracheitis in calves]. AB - The pathogenesis of mixed experimental infection caused by intranasal inoculation of seronegative calves aged 4-6 months with bovine viral diarrhea-mucosal disease (BVDMD) (cytopathogenic) and infectious bovine rhinotracheitis (BRT) viruses, was studied. Consecutive injections of viruses resulted in acute respiratory disease that was severer and accompanied by necrotic rhinotracheitis and acute catarrhal bronchopneumonia than individual injections. BVDMD virus was reisolated from the samples taken from the respiratory tract, intestine, and lymphoid system. The longer excretion of BRT virus with nasal swabs and its high concentration in the respiratory organs suggests its more potent pathogenic properties during reproduction of BVDMD virus. PMID- 17722613 TI - [Surgical treatment of iatrogenic lesions of the urinary tracts and their complications]. AB - The article presents results of surgical treatment of 167 patients with iatrogenic urinary tract lesions made in the course of various surgical interventions. Ureteral trauma was detected in 106 (63.5%), urinary bladder trauma--in 44 (26.3%), urethral trauma--in 5 (3.0%) and trauma of the bladder and ureters--in 12 (7.2%) patients. Endoureterotomy was made in 7 (4.0%) patients with short ureteral stricture, intraoperative correction of ureteral injuries was made in 8 (4.6%) cases. Ureteroplasty according to the technique designed by the authors was conducted in one female patient. A variant of ureterocystoanastomosis (UCA) was created in 67 (38.8%) patients. Reconstruction of the urinary tract with an ileal graft was performed in 16 (9.3%) patients, with the appendix--in 4 (2.3%) patients. Intestinal plastic correction of the ureters and urinary bladder was made in 2 (1.2%) patients. In trauma of the urinary bladder in 3 (1.7%) patients it was sutured, 41 (23.7%) patients underwent transvaginal vesicofistuloraphy. Electrocoagulation of the vesicovaginal fistula and colpocleisis were performed in 8 (4.6%) patients. Plastic surgery of vesicorectal and urethrovaginal fistula was conducted in 3 (1.7%) and 5 (2.9%) patients, respectively. In postoperative period after reconstructive operations complications developed in 17 (10.2%) patients. Conservative treatment of the complications was carried out in 11 (6.6%) patients, reoperations were made in 6 (3.6%) patients: resection of the stricture of appendicocystoanastomosis with reanastomosis (n = 1), repeat UCA (n = 1), revesicofistuloraphy (n = 1) and electrocoagulation of recurrent fistula (n = 3). Rehabilitation was achieved in 98.8% patients. Obstruction of the ureters and urogenital fistulas are prevailing complications (93.4%) of iatrogenic injury of the urinary tract. Operations of choice in such complications are UCA and transvaginal fistuloraphy, respectively. PMID- 17722612 TI - [ELISA and PCR test systems used to detect Crimean-Congo hemorrhagic fever virus]. AB - Studying the sensitivity and specificity of enzyme-linked immunosorbent assay (ELISA) for the indication of Crimean-Congo hemorrhagic fever (CCHF) virus antigens and those of reverse transcription and polymerase chain reaction (RT PCR) for the detection of CCHF virus RNA, and those of a intercerebral infection method in newborn albino mice systems for the determination of viral infectious activity established that the sensitivity of ELISA was 1-2 orders of magnitude less than that of RP-PCR. The latter proved to be better in studying the sera sampled from patients with CCHF. The results of studying the samples of H. marginatum ticks, the CCHF virus vectors by ELISA and RT-PCR were similar. PMID- 17722614 TI - [Trospium chloride (spasmex) in the treatment of lower urinary tract symptoms in patients with neurogenic hyperactive urinary bladder caused by vertebrogenic lesions]. AB - The study included 62 patients (30 males and 32 females, age 19-80 years, duration of the disease 2-28 years) with vertebrogenic disease suffering from urgent, frequent voiding. All the patients have undergone detailed urodynamic and general urological examination monthly before and after treatment. Spasmex was given orally to 16 patients of group 1 (15 mg/day), 24 patients of group 2 (30 mg/day) and 22 patients of group 3 (45 mg/day) once a day for 6 months. It is shown that spasmex in doses 15, 30 and 45 mg was highly effective and well tolerated. Spasmex in a dose 45 mg/day not only significantly reduced the number of urinations but also increased cystometric capacity and mean effective volume of the bladder, reduced the number of urgent voiding. Main side effects of the drug were xerostomia and constipation the frequency of which was the same in all the groups. PMID- 17722615 TI - [Solifenacin in the treatment of patients with hyperactive urinary bladder]. AB - Efficacy and tolerance of a novel antimuscarinic drug solifenacin succinate (vesicar) were studied in 55 patients with hyperactive urinary bladder (HUB). All the patients were divided into two groups: 27 patients of group 1 received solifenacin in a dose 5 mg/day, 28 patients of group 2--in a dose 10 mg/day. The 3-month treatment has improved symptoms of the HUB compared to the initial level: a daily number of vesical tenesmus reduced in patients of groups 1 and 2 by 47 and 51%, respectively; a number of episodes of urgent urine incontinence by 53 and 65%, voiding--by 24 and 26%, respectively. Most symptom incidence reduction (by 2/3) occurred within the first month of therapy. Tolerance to 5 and 10 mg/day solifenacine was satisfactory. The most frequent side effect was xerostomia (18.5 and 28.5%, respectively). The results of the study show that solifenacine in doses 5 and 10 mg/day is effective and safe drug for therapy of patients with hyperactive urinary bladder. PMID- 17722616 TI - [Fracture of the penis]. AB - Rupture of the cavernous bodies is a serious penile trauma which may result in severe long-term consequences. Standard suturing of the cavernous body is accompanied with posttraumatic complications: erectile dysfunction and distortion of the penis. The results of examination and treatment of 38 patients with rupture of the tunica albuginea of the penile cavernous bodies are presented. The technique of the cavernous body wound suturing was perfected. Long-term sequences of fracture of the penis in conservative policy and different methods of cavernous body wound suturing are compared. PMID- 17722618 TI - [Use of cernilton in the therapy of prostatic adenoma and chronic prostatitis]. AB - Cernilton is a phytodrug containing pollen extract. It has antiandrogenic and anti-inflammatory effects influencing alpha1-adrenoblockers located in the zone of the detrusor and urethra. A conservative therapy with cernilton was given to 72 patients with chronic prostatitis and prostatic adenoma of stage I-II. Detailed urologic examination before the treatment and after it demonstrates that cernilton is effective, safe and well tolerated medicine for prostatic adenoma and chronic prostatitis. Cernilton is recommended for wider use in the treatment of patients with prostatic adenoma and chronic prostatitis. PMID- 17722617 TI - [Hypospadia in females]. AB - Hypospadia is a frequent birth deformity consisting in fissure of the posterior (lower) wall of the urethra. Hypospadia is characterized by shortening of the urethra and ectopia of the external urethral opening. This deformity often occurs in women but is rarely diagnosed because physicians are not well-informed about female hypospadia. Classification of anatomic variants of female hypospadia proposed by the authors includes low vaginal ectopia of the external urethral opening; high vaginal ectopia of the external opening of the urethra; urovaginal (vesicovaginal) fusion of the neck of the urinary bladder with vagina accompanied with enuresis; urogenital sinus in females (ectopia of the external urethral opening in the urogenital sinus); any of the above variants of female hypospadia in combination with false or true hermaphroditism. All the variants of female hypospadia must be surgically corrected as transposition of the external opening of the urethra from the vagina on the perineum under the clitoris in chronic urethritis, cystitis and vulvovaginitis or as urethroplasty in enuresis. Hypospadia, urogenital sinus and hermaphroditism--three anomalies of human urogenital system--combine rather frequently. PMID- 17722619 TI - [Vitaprost forte in the therapy of patients with prostatic adenoma]. AB - Active substance of the drug vitaprost is a complex of water-soluble biologically active peptides isolated from bovine prostatic gland. Prostatic extract has an organotropic effect in respect to the prostatic gland. It inhibits proliferative activity of cells and, therefore, development of prostatic adenoma, reduces edema and inflammation activity in prostatic diseases. Our study has shown that rectal suppositories vitaprost forte, as monotherapy of prostatic adenoma, produces a statistically significant moderate decrease of prostate size. The resultant infravesical obstruction also diminished this manifesting with increased maximal and mean volumetric urine flow rate and low volume of residual urine. A decline in obstructive and irritative symptoms due to vitaprost forte was confirmed by IPSS scores showing deterioration of quality of life. Rectal suppositories vitaprost forte can be used as monotherapy of prostatic adenoma in patients with moderate infravesical obstruction irrespective of age and concurrent diseases. PMID- 17722620 TI - [Asymptomatic genital herpes infection and infertility in males]. AB - Incidence of Herpes simplex virus (HSV) was studied in ejaculates of 100 men. The examinees had neither history nor clinical symptoms of HSV genital infection. HSV was detected by a rapid cultural method in the ejaculate of 20 out of 100 examinees (20%). Of 67 males with infertility HSV was detected in 25%, in 19 males examined prophylactically and 14 patients with varicocele (a comparison group) it was found in 10.5 and 7% cases, respectively. Oligozoospermia was two times more frequent in HSV-containing ejaculates than in HSV-negative one. Mean values of the majority of sperm parameters in HSV-positive and HSV-negative groups did not differ statistically. However, it was revealed that such damage of the spermatozoa structure as microhead (consequence of the defective acrosome or reduced genome) and cytoplasm drops on the neck (a sign of immature forms) occurred more often in HSV-infected patients than in persons with HSV-negative ejaculate. Thus, asymptomatic HSV infection has a negative effect on male fertility. PMID- 17722621 TI - [Herpetic infection of spermatozoa in failure of reproductive technologies and spontaneous abortion]. AB - Herpes simplex virus (HSV) was studied in ejaculate of 36 men whose wives had the history of spontaneous abortions, or failure of artificial insemination (AI), or extracorporeal fertilization (ECF). The control group consisted of 222 patients examined prophylactically after urogenital inflammation or for primary infertility. HSV was detected with immunofluorescence (IF) reaction with monoclonal antibodies to HSV antigens, rapid culture method (RCM) and transmission electronic microscopy. HSV antigens were detected in fraction of mobile spermatozoa in 13 (65%) of 20 samples from patients of the study group. HSV detectability in the study group was significantly higher than in the controls (p = 0.003). Intragametic capsides of HSV were detected at ultrastructural investigation in 13 of 19 (68%) ejaculate samples from patients of the study group in whom IF and/ or RCM results were positive. The study of 6 ejaculate samples of this group in which HSV was not detected by IF or RCM and 24 control samples HSV capsides were not detected. The following conclusions can be made: mobile spermatozoa of normal morphology can be infected with HSV; as shown morphologically, samples of ejaculate from men whose wives had spontaneous abortions contained intragametic HSV capsides; intragametic HSV infection of spermatozoa had a negative effect on the course of pregnancy and/or embryon vitality. PMID- 17722622 TI - [Bilateral varicocele: epidemiology, clinical presentation and diagnosis]. AB - Epidemiology of bilateral varicocele (BV) was studied in 2600 patients with varicocele and in 3900 infertile patients 1196 of whom had varicocele. The diagnosis was made by examination, palpation of sexual organs, dopplerography. In addition, causes and clinical picture of BV were investigated. Targeted urological examination of 8000 schoolchildren detected varicocele in 1704 (22.8%) examinees, of them BV was in 290 (3.3%). Detailed examination with ultrasound in 1500 varicocele patients detected BV in 519 (34.6%). Among 1100 varicocele patients BV was detected after detailed examination in 328 (36%), after physical examination--in 156 (14.2%). Of 2900 infertile patients varicocele was diagnosed in 1196 patients, BV--in 312. After detailed examination BV incidence reached 41.2. Superselective testiculoflebography and multispiral computed tomography detected that in many BV patients right internal seminal vein enters the right renal vein. Asymptomatic right-side BV was detected in 1195 (96/0%) of 1245 BV patients, 397 (37.6%) patients with left-side BV had pain at exercise. At ultrasound examination the diameter of the scrotal part of the semenal vein in BV patients with right and left side disease in subclinical varicocele was from 1.5 to 4 mm (2.5 mm), in degree I--3-4 mm, in degree II--3.1-5 mm, in degree III--5.1 7.0 mm (in some cases up to 9 mm). The return blood flow rate in subclinical varicocele reached 0.100-0.120 m/s, in varicocele of the first degree--up to 0.150, of the second degree--up to 0.300 m/s and third--over 0.300 m/s. Thus, BV occurs much more often than is diagnosed. Adequate diagnosis rate can be achieved in using ultrasound methods. PMID- 17722624 TI - [Optimization of diagnostic and therapeutic tactics for primary megaureter in children]. AB - Obstructive megaureter (MU) and refluxing MU were treated in 2000-2004 in 580 and 711 children, respectively. This number was by 18.9% higher than in 1990-1994. Out of 1291 children with MU, two groups of patients were singled out: group 1 with primary obstructive MU (n = 158) and group 2 with primary refluxing MU (n = 185). In patients of groups 1 and 2 the following operations were made: ureteral reimplantation (n = 126), Koen's operation (n = 104), Politano-Leadbetter operation (n = 12), Lich-Greguaru operation (n = 8), nephrureterectomy (n = 32), heminephrureterectomy (n = 27), transurethral dissection of ureterocele (n = 8), other in 26 patients. A great number of primary nephrureterectomies evidence for frequent morphofunctional immaturity of one of the kidneys in children with primary MU forms. The 1.5-6 year follow-up results were good in 85.4% children of group 1 and 94.1% children of group 2. In planning follow-up and assessing long term follow-up results morphofunctional state of the kidney and ureter before and after operation must be considered according to the following main criteria: dilation of the caliceal-pelvic system and ureter, renal function, pyelonephritis activity, the presence or absence of recurrent stricture of the distal ureteric segment or the presence of vesicoureteral reflux. PMID- 17722623 TI - [Changes in lower urinary tract function in children with hyperactive urinary bladder treated with combined therapy]. AB - Low clinical efficacy of M-cholinolytics remains a serious problem in conservative therapy of hyperactive bladder (HB). To improve treatment outcomes, combined therapy (pikamilon plus driptan) was tried in 22 boys and 25 girls aged 7 to 14 years. The children were examined with uroflowmetry, cystometry. The response to the treatment was found to depend on mean effective capacity of the urinary bladder. Duration ofurodynamic correction has a negative colleration with this capacity. Urodynamic investigations performed in different periods of therapy show that improvement of lower urinary tract function is pathogenetically important for treatment of children with urologic pathology running in the presence of hyperactive urinary bladder. PMID- 17722625 TI - [Modern algorithm of examination and treatment of patients with prostatic adenoma]. PMID- 17722626 TI - [Bilateral retroperitoneoscopic ureterolithotomy (clinical case)]. PMID- 17722627 TI - [Giant ureteral stones]. PMID- 17722628 TI - [Acute urine retention in prostatic adenoma]. PMID- 17722629 TI - [The role of estriol in therapy of urogenital disorders in postmenopausal women]. PMID- 17722630 TI - [Pathogenetic pharmacotherapy of erectile dysfunction]. PMID- 17722631 TI - [Noninflammatory syndrome of chronic pelvic pain in men (history of the problem)]. PMID- 17722632 TI - [Psychosomatic disorders in officers of special military forces with Internal Ministry: incidence, secondary prophylaxis]. AB - The authors defined incidence of psychosomatic disorders in officers participated in counter-terrorist operations. Studies covered therapeutic influence of complex rehabilitation and recreation on anxious and depressive conditions, on premorbid hemodynamic changes. PMID- 17722634 TI - [Influence of occupational environment on coronary heart disease incidence in automobile transport drivers]. AB - The authors revealed quite high incidence of coronary heart disease and its risk factors among automobile transport drivers due to occupational peculiarities, deterioration in operative response system in patients with coronary heart disease and arterial hypertension. The suggestion is to review official medical indications for driving license. PMID- 17722633 TI - [Cardiovascular diseases in female workers and methods of their prevention]. AB - The article covers actual incidence of coronary heart disease and arterial hypertension, atherosclerosis risk factors among female workers, its dependence on age and occupation type. The authors studied efficiency and safety of antihypertensive therapy in hypertensive women. PMID- 17722635 TI - [Epidemiology of arterial hypertension and atherosclerosis risk factors in female Internal Ministry officers]. AB - The authors revealed prevalence of arterial hypertension and atherosclerosis risk factors among female Internal Ministry officers, demonstrated influence of occupational activities on frequency of the studied parameters and on cardiovascular risk. PMID- 17722636 TI - [Myocardial infarction at young age]. AB - The authors revealed incidence of myocardial infarction and risk factors at young age, clinical peculiarities, prevalence of atherosclerosis risk factors in male workers aged 20-39. PMID- 17722637 TI - [Register of arterial hypertension in rural region]. AB - The authors determined incidence of arterial hypertension and its risk factors among rural cattle-breeders and car drivers, presented data on prevalence of major cardiovascular diseases in population, on actual situation concerning secondary prophylaxis of arterial hypertension, demonstrated efficiency of antihypertensive therapy for male and female hypertensive patients, stressed the role of systematic training of medical staffers and patients in decreasing cardiovascular morbidity. The data obtained served as a basis for "Register of arterial hypertension in rural region" database to be used for efficient management of arterial hypertension in rural area. PMID- 17722638 TI - [Taxonomy and evolution of the genus Pratylenchoides (Nematoda: Pratylenchidae)]. AB - The amended diagnosis of the genus Pratylenchoides and list of its valid species with synonyms are given. All the efficient diagnostic characters are listed. Modern taxonomic standard for the description of Pratylenchoides species is proposed; it may be used also in taxonomic databases. Tabular and text keys for all species of the genus are given. Five following groups are considered within the genus Pratylenchoides. The group arenicola differs from other groups in the primitive adanal bursa type; the groups magnicauda, crenicauda, ritteri, and megalobatus differ from each other in the position of cardium along the body axis in relation to the pharyngeal gland nuclei, pharynx types are named according to the stages of its evolution from the primitive tylenchoid pharynx (cardium situated posteriorly) to the advanced hoplolaimoid one (cardium situated anteriorly). Diagnoses and species compositions of the groups are given. Basing on the matrix of species characters, the dendrogram has been generated for all species of Pratylenchoides and for all characters (UPGMA, distance, mean character difference, random, characters ordered). Taking in view that the PAUP software gives equal weights to all characters, including the most important ones which define the prognostic species groups, the separate dendrograms for each prognostic species group were generated using the same above mentioned tree parameters. On the base of the records of Pratylenchoides species the matrices of plant host ranges, geographic distribution, and preferred soil-climatic conditions were developed. The dendrograms of the faunal similarities were generated using these matrices, with conclusions on a possible origin and evolution of the genus. The genus evolved from the flood lands with swampy soils and prevalence of dicotyledons (herbaceous Lamiaceae and woody Salicaceae families) to the forest mainland communities with balanced humidity and predominance of herbaceous Poaceae and Fabaceae with woody Fagaceae, Betulaceae, and Oleaceae. The leading factor of the evolutional adaptation to soil-climatic conditions was the factor of humidity, but its significance gradually decreased with the host change to more advanced plant taxa adapted to the communities with more dry balanced humidity. The genus took its origin on the south shores of Laurasia in the Cainozoe. Later, when Hindistant and Arabian Peninsula joined with Laurasia creating the Himalayas barrier, the Pratylenchoides spp. distributed by two branches: the northern one moved into Central Asia, East Europe and North America, and the south branch came into Indo-Malaya, West Asia and the north of Africa. The remnants of the ancient species groups remain in West Europe and East Asia. In the North America the genus gave an origin to its sister genus Apratylenchoides, which spread to the south up to Antarctica; another advanced branch spread in the North America reaching Alaska. PMID- 17722639 TI - [Invasion character and distribution of the Diplostomum huronense (La Rue, 1927) Hugnes, 1929 metacercariae in roach of Lake Ladoga]. AB - Estimation of the invasion character and distribution of the Diplostomum huronense metacercariae depending on the fish host age has been carried out in roach of Lake Ladoga. Distribution of D. huronense in the young roach (up to age 5+) is negative binomial. Aggregation of the parasite is caused not only by individual differences in the fish host resistance to the metacercariae invasion, but by a high mortality of hyperinfected fishes as well. In older individual hosts the host-parasite system is destroyed, and the parasite distribution approximates to normal. The parasite system of the diplostomids in roach is characterized by the spatial asymmetry, when most part of parasites inhabit few individual hosts, and probability of the case when a parasite get into previously infected host is higher than that of the invasion of parasite-free host. Thus, the Diplostomum huronense metacercaria is an important factor regulating the fish fry number both in direct (death of infected fry) and indirect (elimination of hyperinfected fishes by ichthyophagous birds) way. PMID- 17722640 TI - [Helminth fauna in insectivores (Mammalia: Insectivora) of canal banks in meliorated territories]. AB - Helminth fauna of Insectivora was investigated in canal banks situated in meliorated territories of Belorussian Polesie during 1996-1999. Thirty-three helminth species were found in the animals examined. Most of the parasites are usual in common shrew Sorex araneus L., which is a predominate insectivore species in canal banks. PMID- 17722642 TI - [Palpal sensory organ in the chicken mite Dermanyssus gallinae (Acari: Dermanyssidae)]. AB - Palptarsus of the chicken mite bears 5 single-wall upper-pore (SW-UP) chemo mechanoreceptor sensilla (type A); 4 double-wall upper-pore (DW-UP) chemosensitive sensilla (type B), and 6 no-pore (NP) mechanoreceptor sensilla (type M). The author assumes that sensilla of the type A participate in perception of the aggregation pheromone; of the type B, in perception of trophic stimuli; and of the type M, in determination of mechanical properties of the substrate. PMID- 17722641 TI - [Dispersal of the flea Ctenophyllus hirticrus and spreading of plague epizooties in Gorny Altai]. AB - Gradual dispersion of an abundant flea species Ctenophyllus hirticrus specific to the Pallas's pika (the main plague carrier), is revealed in the Gorno-Altai natural plague focus on the territory, occupied by two populations of this lagomorph. Spreading of Yersinia pestis in these areas took place a short time later the rise of this ectoparasite's abundance. It is supposed that the colonization of these areas by C. hirticrus was one of the factors determined epizooties spreading within the focus and formation of new sites of stable Y. pestis preservation. PMID- 17722643 TI - [Species composition and ecological peculiarities of the blood-sucking mosquito genus Ochlerotatus (communis species group) (Diptera: Culicidae) of the Novgorod Province]. AB - Eleven mosquito species of the communis species group (genus Ochlerotatus, family Culicidae) were found in the Novgorod Province as a result of nine-year investigations (1996-2004). Ochlerotatus impiger, O. nigrinus, and O. sticticus are recorded in the Novgorod Province for the first time. PMID- 17722644 TI - [Skin lesions in small mammals parasitized by Psorergates apodemi and P. dissimilis (Gheyletoidea: Psorergatidae)]. AB - Histopathology in the sites of localization and parasiting of the mites Psorergates apodemi Fain et al., 1966 and P. dissimilis Fain et al., 1966 on the Ural field mouse Apodemus uralensis (Pallas) and the bank vole Clethrionomys glareolus (Schreber) is described. The mites affected all epidermis cell layers down to the cambium layer and caused hyperkeratosis. PMID- 17722645 TI - Transporters in the intestine limiting drug and toxin absorption. AB - The pharmacokinetic behaviour of drugs strongly depends on transporters in intestine and liver. The extent of absorption in the intestine depends on diffusion across the mucosa as well as transporter-mediated uptake across the apical membrane of enterocytes. Efflux pumps in this membrane may strongly reduce the extent of net uptake. These efflux pumps are ATP-binding cassette (ABC) transporters which are also expressed in the apical membrane of the hepatocyte were they mediate excretion into bile. This combined activity strongly determines whether drugs have access to the systemic circulation. PMID- 17722646 TI - Using genomics to understand intestinal biology. AB - The use of microarrays to evaluate the transcriptome has transformed our view of biology. In addition to the focused, hypothesis-testing studies that we have traditionally conducted in cell biology, we are now able to see global changes within the entire system of the cell in response to a treatment. By examining a biological question under multiple complementary perturbations model systems (e.g. yeast, C. Elegans) have revealed new complexity that would have been impossible to see on a gene-by-gene approach. Unfortunately, beyond the use of transcript profiles to define the molecular signature of diseases (e.g. cancer), transcriptomics has not been extensively used to study intestinal biology. This review will provide a roadmap for effective use of gene expression profiling for biological research and will review some of the microarray work that has been done to better understand the nature of intestinal development and enterocyte differentiation. PMID- 17722648 TI - DNA protein interactions at the rRNA of Saccharomyces cerevisiae. AB - The rDNA cluster is the genetic locus encoding the ribosomal RNAs and physically defines where ribosomes begin to be assembled. In the yeast Saccharomyces cerevisiae, the highly repetitive structure of this locus makes it a very interesting target for studies about genome stability, chromatin-mediated transcriptional silencing and progression of aging. In fact, recombination among the repeated units is suppressed in a WT cell. Moreover, when genes transcribed by RNA polymerase II are inserted in the rDNA cluster, their transcription is silenced. Finally, the formation of rDNA minicircles (ERCs) has been shown to be one of the causes of aging in yeast. DNA topoisomerase I have been shown to suppress recombination specifically at the rDNA of S.cerevisiae. Moreover, also the chromatin structure of this locus is affected in a top1 strain, because rDNA specific transcriptional silencing is abolished. Nonetheless, the molecular basis of how this enzyme interferes with these functions is yet unknown. Here are reported results obtained by in vivo studies of DNA protein interactions occurring on the rDNA locus. The analyses include a fine mapping of nucleosome positioning; RNA polymerase I transcription factors and DNA topoisomerase I cleavage sites. Important conclusions can be drawn: i) nucleosome positioning in the Non Transcribed Spacer is not affected by RNA polymerase I transcription; ii) the RNA polymerase I transcription factors bind DNA in vivo with a defined hierarchy; iii) the DNA topoisomerase I cleaves the NTS in very specific sites, but cleavage is not induced by RNA polymerase I transcription. These in vivo studies help to characterize the molecular basis of important phenomena as the transcriptional silencing and genome stability in yeast. PMID- 17722650 TI - Reverse gyrase: an unusual DNA manipulator of hyperthermophilic organisms. AB - Reverse gyrase is the only DNA topoisomerase capable of introducing positive supercoiling into DNA molecules. This unique activity reflects a distinctive arrangement of the protein, which is composed of a topoisomerase IA module fused to a domain containing sequence motives typical of helicases; however, reverse gyrase works neither like a canonical topoisomerase IA nor like a helicase. Extensive genomic analysis has shown that reverse gyrase is present in all organisms living above 70 degrees C and in some of those living at 60- 70 degrees C, but is invariably absent in organisms living at mesophilic temperatures. For its peculiar distribution and biochemical activity, the enzyme has been suggested to play a role in maintenance of genome stability at high temperature. We review here recent phylogenetic, biochemical and structural data on reverse gyrase and discuss the possible role of this enzyme in the biology of hyperthermophilic organisms. PMID- 17722649 TI - Human DNA topoisomerase IB: structure and functions. AB - Human DNA Topoisomerase I is a 765aa monomeric enzyme composed of four domains: the N-terminal domain, highly charged and responsible for several protein-protein interactions, the core domain that embraces the DNA during catalysis, the highly charged linker domain and the C-teminal domain containing the active site. The enzyme promotes the relaxation of supercoiled DNA by nicking and rejoining one of the strands of the DNA. Its activity is critical for many biological processes including DNA replication, transcription, and recombination. The aim of this review is to analyze the enzyme activity in terms of structure-function relationship. PMID- 17722647 TI - Concentrative nucleoside transporters (CNTs) in epithelia: from absorption to cell signaling. AB - Concentrative and Equilibrative Nucleoside Transporter proteins (CNT and ENT, respectively) are encoded by gene families SLC28 and SLC29. They mediate the uptake of natural nucleosides and a variety of nucleoside-derived drugs, mostly used in anticancer therapy. CNT and ENT proteins are mostly localized in the apical and basolateral sides, respectively, in (re)absorptive epithelia. This anatomic distribution determines nucleoside and nucleoside-derived vectorial flux. CNT expression (particularly CNT2) is associated with differentiation and is also nutritionally regulated in intestinal epithelia, whereas ENT protein amounts (mostly ENT1) are increased when cells are exposed to proliferative stimuli such as EGF, TGF-alpha or wounding. Although all these features suggest a role for NT proteins in nucleoside salvage and (re)absorption, recent data demonstrate that CNT2 might be under purinergic control, in a manner that is dependent on energy metabolism. A physiological link between CNT2 function and intracellular metabolism is also supported by the evidence that extracellular adenosine can activate the AMP-dependent kinase (AMPK), by a mechanism which relies upon adenosine transport and phosphorylation. Thus the complex pattern of NT isoform expression in mammalian cells can fulfill physiological roles other than salvage. PMID- 17722651 TI - Role of flexibility and long range communication on the function of human topoisomerase I. AB - Eukaryotic topoisomerase I is an essential enzyme that regulates the changes in DNA topology, relaxing the superhelical tension associated with DNA replication, transcription and recombination. Human topoisomerase I is of significant medical interest being the only target of the antitumor drug camptothecin. The enzyme undergoes large conformational changes during its catalytic cycle and the knowedge of the degree of flexibility of the different regions provides an useful guide to the understanding of such movements. Molecular dynamics simulation is a well consolidated method for the investigation of structural and dynamic properties of proteins and nucleic acids and has been successfully applied to study the dynamical properties of the DNA-human topoisomerase complex. This review highlights some structural and dynamic properties of topoisomerase, obtained by MD simulations, that permits to explain the importance of flexibility in the modulation of the functional properties of the enzyme and in the transmission of communication between domains located far away one from each other. PMID- 17722652 TI - RecQ helicases and topoisomerases: implications for genome stability in humans. AB - In recent years growing evidence has suggested that the RecQ helicases play a crucial role in preserving genome stability. The importance of this observation in humans is substantiated by the fact that the absence of a functional RecQ helicase is associated with genetic syndromes characterised by elevated predisposition to a wide variety of cancers. It is well recognized that maintenance of genome integrity relies on the accurate execution of the DNA replication process as well as on efficient DNA repair. A number of studies have described interactions of RecQ helicases with topoisomerases and it has been proposed that this cooperation may be essential for cell viability and the avoidance of cancer development in human cells. PMID- 17722653 TI - DNA topoisomerase i as a transcription protein and a lethal cellular toxin. AB - DNA topoisomerase I constitutes a significant relaxing activity in nuclei of eukaryotic cells. The enzyme acts during several DNA transactions involving the generation of torsional stress in the DNA template. Moreover, antitumor agents targeting DNA topoisomerase I are used in the treatment of human cancers with significant clinical outcome. Major progress has been attained in recent years in the understanding of the basic cellular functions of DNA topoisomerase I. In particular, the consequences of topoisomerase I activity during transcription have been extensively investigated and constitute still a very active research area. Understanding of topoisomerase I inhibitors emphasizes drug activity against the enzyme, however the high drug potency cannot be explained by the DNA damage outcome only. Even though the understanding of enzyme structure has progressed in last years, however more insights into the activity of topoisomerase I poisons have not been achieved yet. Here, we will review landmark investigations on topoisomerase I involvement in different stages of the transcription process, addressing both enzyme functions as well as drug effects on molecular processes. Moreover, we will discuss recent findings on the targeting of topoisomerase I to pre-selected sites in transcribed chromatin by fusion to a sequence-specific DNA-binding protein domain. PMID- 17722654 TI - Interplay between wrn and the checkpoint in s-phase. AB - Stability of the genome is crucial for survival and faithful transmission of the genetic blueprint to progenitors. During DNA replication chromosome integrity can be challenged by a variety of exogenous and endogenous damaging agents and by the process of duplication itself. Thus, eukaryotic cells have evolved a sophisticated response called replication checkpoint supervising the accurate and complete genome replication. The replication checkpoint response bridges together replication, repair and cell cycle proteins in a coordinated network having the ATR kinase as culprit. ATR-mediated phosphorylation events control that stalled replication forks are properly sensed and stabilised, cell cycle progression halted and replication eventually recovered. In the recent years, the Werner syndrome protein (WRN) emerged as a central actor of the replication checkpoint being instrumental for correct recovery from arrested replication and a substrate of ATR. In this review, how WRN and the replication checkpoint could cross-talk and contribute to faithful recovery of stalled replication forks will be discussed. PMID- 17722655 TI - The interplay among chromatin dynamics, cell cycle checkpoints and repair mechanisms modulates the cellular response to DNA damage. AB - Cells are continuously under the assault of endogenous and exogenous genotoxic stress that challenges the integrity of DNA. To cope with such a formidable task cells have evolved surveillance mechanisms, known as checkpoints, and a variety of DNA repair systems responding to different types of DNA lesions. These lesions occur in the context of the chromatin structure and, as expected for all DNA transactions, the cellular response to DNA damage is going to be influenced by the chromatin enviroment. In this review, we will discuss recent studies implicating chromatin remodelling factors and histone modifications in the response to DNA double-strand breaks (DSBs) and in checkpoint activation in response to UV lesions. PMID- 17722656 TI - Purification, kinetic properties and physicochemical characterization of a novel acid phosphatase (AP) from germinating peanut (Arachis hypogaea) seed. AB - Acid phosphatase activity was detected in peanut (Arachis hypogaea) cotyledons during germination. Four (4) to six (6) days of germination was the meantime corresponding to maximum hydrolytic activity of this enzyme. The understanding of the role of acid phosphatase activity during germination led to purify this enzyme by successive chromatography separations on DEAE-Sepharose CL-6B, Sephacryl S-100 HR and Phenyl-Sepharose HP to apparent homogeneity from germinated peanut cotyledon five days old. This enzyme designated peanut cotyledon acid phosphatase (AP) had native molecular weight of 24 kDa by gel permeation. SDS-PAGE of the purified acid phosphatase resolved a single protein band that migrated to approximately 21.5 kDa. Thus, this acid phosphatase likely functions as a monomer. The enzyme had optimum pH (5.0) and temperature (55 degrees C), and appeared to be stable in the presence of anionic, cationic and non-ionic detergents. Substrate specificity indicated that the purified acid phosphatase hydrolyzed a broad range of phosphorylated substrates. However, natural substrates such as ADP and ATP were the compounds with highest rate of hydrolysis for the enzyme. Moreover, the purified acid phosphatase exhibited phytase activity. These results showed that this enzyme played a peculiar role during germination, notably in reducing the rate of phytic acid, an antinutritional substance contained in peanut seed. PMID- 17722657 TI - Characterization of dextransucrase immobilized on calcium alginate beads from Leuconostoc mesenteroides PCSIR-4. AB - Immobilization of dextransucrase from Leuconostoc mesenteroides PCSIR-4 on alginate is optimized for application in the production of dextran from sucrose. Dextransucrase was partially purified by ethanol upto 2.5 fold. Properties of dextransucrase were less affected by immobilization on alginate beads from soluble enzyme. Highest activities of both soluble and immobilized dextransucrase found to be at 35 degrees C and optimum pH for activity remain 5.00. Substrate maxima for immobilized enzyme changed from 125 mg/ml to 200 mg/ml. Incubation time for enzyme-substrate reaction for maximum enzyme activity was increased from 15 minutes to 60 minutes in case of immobilized enzyme. Maximum stability of immobilized dextransucrase was achieved at 25 degrees C with respect to time. PMID- 17722659 TI - Nitrogen effects on proteins, chlorophylls and fatty acids during the growth of Arthrospira platensis. AB - Spirulina platensis (=Arthrospira platensis) is a tunisian strain which has been isolated for the first time in Oued Essed (Sousse, Sidi Bou Ali). Biomass evolution, proteins, chlorophylls and fatty acids composition of this alga were monitored by varying nitrogen concentrations in the culture medium. Nitrogen stress was provoked by adding sodium nitrate (NaNO3) in the culture medium with concentrations varying from 0 to 5 g/l. Results obtained showed that nitrogen depletion increased total proteins and total chlorophylls. The addition of NaNO3 (5g/l) led to an increase of total fatty acids amounts and modify fatty acids composition. Optimal quantities of palmitic, gamma -linolenic and oleic acids were obtained with NaNO3 free-cultures. Thus, the tunisian strain has valuable biological substances, worthy to determine the optimal conditions for its propagation. PMID- 17722658 TI - Simultaneous purification and polymerization method for bovine serum albumin preparation. AB - Bovine serum albumin (BSA) has various applications in blood group serology and different research purposes. In this study purification of BSA has been compared with human serum albumin (HSA) using modified ethanol precipitation method based on the method of Cohn. The purification process was carried out under controlled conditions, particularly of ethanol concentration, pH, ionic strength and temperature. It was revealed that the produced BSA and HSA have purity more than 95%. It is obvious that HSA can be used, as a drug when the amount of its polymers is less than 5% whereas polymer generation is required in order to enhance the potentiating properties of BSA in agglutination of red cells. We propose here a simple and rapid two-step method for simultaneously purification and polymerization of BSA. By this method simply BSA with desired amount of polymers was obtained by 40% ethanol concentration. PMID- 17722660 TI - Estimation of total and direct serum bilirubin using modified micro assay method. AB - Estimation of total and direct bilirubin in serum plays an important role in differential diagnosis of hyperbilirubinemia. Several direct spectrophotometric methods are commercially available for total and direct bilirubin estimation in which the amount of the sample (serum) varies from 200 ml to 800 ml. It is difficult to collect such amount of serum from infants, as neonatal jaundice is the most common problem in this age group. To overcome this problem modified micro assay method was developed using dimethylsulfoxide (DMSO). The amount of the serum sample is reduced from 100 ml to 20 ml per test for both total and direct bilirubin. A method comparison study was performed using 100 consecutive serum samples, by modified micro assay method and a reference Jendrassik-Grof method. Total bilirubin in these human serum samples ranged from 0.4-15.0 mg/dl and direct bilirubin ranged from 0.05-12.0 mg/dl. The results conclude that modified micro assay method had significant correlation with r-value of 0.99989 for total serum bilirubin and with r-value of 0.99971 for direct serum bilirubin. Linearity of the method is 20 mg/dl and 15 mg/dl for total and direct bilirubin, respectively. Monoreagent used during the assay is stable for 24 hours at 2-8 degrees C while the kit is stable for one year at 2-8 degrees C. In conclusion this micro assay method is rapid, reliable, simple and accurate for the estimation of total and direct bilirubin with small serum quantities. It is equally reliable for manual; semi automated and automated chemistry analyzers. PMID- 17722661 TI - Biochemical evaluation of borage (Borago officinalis) rosette leaves through their essential oil and fatty acid composition. AB - Borago officinalis rosette leaves were sampled in the region of Amdoun (Tunisia) during different stages of their development. Essential oil contents varied from 0.01% to 0.13% respectively in young and adult leaves. Twenty three volatile compounds were identified. Hydrocarbons, mainly represented by nonadecane (29.8%), tetracosane (11.3%) and heptacosane (4.7%), constituted the major class in the young leaves (45.8%), followed by aldehydes (22.4%). The percentages of these two classes decreased to reach respectively 15% and 8.1% in adult leaves in favour of alcohols (57.9%) where cis-3-hexenol (29.6%) and hexanol (14.5%) were the main compounds. Total fatty acids amounts increased from 5.03 mg/g DW in young leaves to 32.23 mg/g DW in adult ones. The predominant fatty acids were alpha-linolenic (C18:3 n-3), stearidonic (C18:4 n-3), gamma-linolenic (C18:3 n 6), palmitic (C16: 0) and linoleic (C18:2 n-6) acids. PMID- 17722662 TI - Essential oil composition of two myrtus communis L. varieties grown in North Tunisia. AB - Two Myrtus communis varieties (var. italica and baetica) were studied in order to investigate their essential oil yield and composition. Essential oil yield varied in leaves, fruits and stems. So, in leaves, it was 0.5% for italica and 0.3% for baetica and was higher than in fruits and stems with respectively 0.1% and 0.04% for italica and 0.07% and 0.03% for baetica. The essential oil analysis performed by GC and GC/MS showed a composition characterized by a high percentage of monoterpene hydrocarbons in leaves, largely due to alpha-pinene with 51.3% for italica and 27.7% for baetica; 1,8-cineole, the alone compound of ether class, was predominant in fruits and stems with respectively 31.6% and 34.7% for italica and 19.8% and 25.8% for baetica. PMID- 17722663 TI - Overcoming barriers to glycemic control in African Americans with type-2 diabetes: benefits of insulin therapy. AB - A disproportionate number of African-American men and women are affected by obesity and diabetes. The documented rate of poor glycemic control in the African American population may contribute to the high rate of morbidity and mortality due to diabetes observed in these patients. Since the benefits of strict glycemic control have been demonstrated in multiple large trials, the aim of treatment should be to achieve the goals set forth by the American Diabetes Association. Insulin remains an essential therapeutic agent for helping patients achieve glycemic control and preventing long-term comorbidities. However, barriers to insulin therapy exist for both the physician and patient. Strategies to counter this resistance include identifying barriers to treatment, restoring the patient's sense of control, utilizing simple regimens, and reviewing the benefits of insulin and the risk of hypoglycemia. In treating African-American patients with diabetes, providers of various racial and ethnic backgrounds may maximize treatment efficacy by attempting to understand and practice culturally competent care. PMID- 17722664 TI - Beyond misdiagnosis, misunderstanding and mistrust: relevance of the historical perspective in the medical and mental health treatment of people of color. AB - In this article, we discuss the relationship and relevance of the historical interaction primarily between African-American culture and the medical and mental health communities, and explore the role of historical experience in contributing to mistrust and underutilization of services by people of color. We conclude that failure on the part of practitioners to go beyond clinical history gathering to recognize and acknowledge the larger historical perspectives from which they and their patients of color draw conclusions and make decisions contributes to the mistrust of the medical and mental health communities and to perpetuation of the current climate of healthcare disparities. PMID- 17722665 TI - Patient satisfaction in specialized versus nonspecialized adult sickle cell care centers: the PiSCES study. AB - BACKGROUND: Sickle cell disease (SCD) patients can receive their ambulatory care from either SCD specialists (caregivers with sickle cell-only clinics) or nonspecialized care centers. Patient satisfaction, an important factor that may influence compliance and outcome, can differ between the two groups because of the perceived quality of care, outcomes or practice style. METHODS: We administered a patient satisfaction survey to 308 participants in an SCD prospective cohort study. Of the 308 patients, 133 (43.2%) received the majority of their SCD care at specialized centers, 152 (49.3%) received their care from nonspecialized centers and 26 (7.5) did not provide information. The satisfaction surveys measured general satisfaction (GS), technical quality (TQ), interpersonal manner (IM), communication (CM), financial aspects (FA), time spent with doctor (TA), and accessibility and convenience (AC). Patients reported their levels of satisfaction using a five-point Likert scale. We compared unadjusted group means, as well as means adjusted for potential confounders such as marital status, on patient satisfaction between specialized and nonspecialized centers. RESULTS: SCD patients who received their care from specialized centers had significantly higher mean satisfaction scores, compared to those who received their care from nonspecialized centers: GS 4.00(+/-0.93) vs. 3.66 (+/- 01.16, p=0.0326), TQ 3.98 (+/- 0.77) vs. 3.65 (+/- 0.91, p=0.0058), AC 3.83 (+/-0.79) vs. 3.51 (+/- 1.02, p=0.0142) , FA 3.88 (+/-0.96) vs. 3.49 (+/-1.25, p=0.0120). There were no statistically significant group differences in IM, TA and CM. CONCLUSION: SCD patients who received most of their SCD care from specialized centers had somewhat higher satisfaction scores in some areas when compared with patients who received their care from nonspecialized centers. PMID- 17722666 TI - Total antioxidants status and some hematological values in sickle cell disease patients in steady state. AB - Congenital hemoglobin mutations may alter the delicate balance of free-radical generation and antioxidant defense systems in the red cell. Oxidative stress may thus play a role in the pathophysiology of the clinical manifestations of the disease. We assessed the total antioxidant status in steady-state sickle cell anemia (SCA) patients and related it to certain hematological parameters and their recent clinical history. Forty (25 males/15 females) adult SCA patients and 30 age-matched controls were studied. All patients and control subjects had total antioxidant status (TAS), hematocrit, white blood cells, platelets and reticulocyte count done. The results showed that TAS levels were about 50% lower in the SCA patients compared with the controls. Among the SCA patients, 57.1% of those with TAS levels <1.00 mmol/L had bone pain crisis >3 times in the past year, compared with 16% in those with TAS levels >1.00 mmol/L. Total leukocyte count and platelets were also significantly higher in the SCA patients than controls. Our data support the growing evidence that oxidative stress has a role to play in the pathophysiology of SCA and intervention aimed at increasing the antioxidant capacity of these patients may be beneficial. PMID- 17722667 TI - Outcomes of men who present with elevated serum PSA (>20 ng/mL) to an inner-city hospital. AB - INTRODUCTION: We report the incidence, clinicopathologic features, and outcomes of men who presented to an inner-city hospital with serum PSA >20 ng/ml. MATERIALS AND METHODS: Five-hundred-sixty men underwent a transrectal ultrasound needle-guided biopsy of the prostate for elevated PSA >4 ng/ml with or without an abnormal digital rectal examination. RESULTS: Of the 560 men, 65 (12%) were found to have a serum PSA >20 ng/ml, and 57 (10%) were diagnosed with prostate cancer. In the group of 57 men with cancer, the positive predictive value of PSA alone was 72% for PSA levels of 20-29.99 ng/ml and 100% for PSA >30 ng/ml. Of the 57 men, 18 underwent definitive therapy, 24 underwent androgen deprivation, 8 refused treatment or were lost to follow-up, and 7 were treated on protocol. An additional seven men with cancer refused therapy or were lost to follow-up, thus giving a total of 15 (26%) men who were noncompliant to medical advice. CONCLUSIONS: Serum PSA >30 ng/ml is an almost certain predictor of the presence of prostate cancer. Aggressive prostate cancer education and screening programs are needed in our inner cities in order to detect prostate cancer at an earlier, treatable stage. PMID- 17722668 TI - Reducing liver cancer disparities: a community-based hepatitis-B prevention program for Asian-American communities. AB - OBJECTIVES: Several Asian-American groups are at a higher risk of dying of liver diseases attributable to hepatitis-B infection. This culturally diverse community should be well informed of and protected against liver diseases. The present study assesses the knowledge of hepatitis B before and after a hepatitis-B educational program and determines the infection status of an Asian community. METHODS: Nine Asian communities of Montgomery County, MD, enrolled in the hepatitis-B prevention program between 2005 and 2006. They attended culturally tailored lectures on prevention, completed self-administered pre- and posttests, and received blood screening for the disease. RESULTS: More than 800 Asian Americans participated in the study. Knowledge of prevention was improved after educational delivery. The average infection rate was 4.5%, with Cambodian, Thai, Vietnamese, Chinese and Korean groups having higher infection rates. The age group of 36-45 had the highest percentage of carriers (9.1%). CONCLUSION: Many Asian groups, particularly those of a southeast Asian decent, were subject to a higher probability of hepatitis-B infection. At an increased risk are first generation Asian immigrants, groups with low immunization rates and those aged 36 45. The findings provide potential directions for focusing preventive interventions on at-risk Asian communities to reduce liver cancer disparities. PMID- 17722669 TI - Relationships among body mass index, parental perceptions, birthweight and parental weight after referral to a weight clinic. AB - OBJECTIVE: We sought to determine whether, in a specialty referral clinic, parental perceptions of their child's obesity were commensurate with the child's body mass index z score. Secondarily, we examined the impact of birth weight and parental body mass index on their child's body mass index z score and review results of an intake questionnaire. DESIGN: Cross-sectional study SETTING: University of Michigan from March 21, 2003 through June 30, 2004 PARTICIPANTS: Eighty-two children ages 1-20.2 years of age INTERVENTION: Body mass index z score for all participants was calculated. An intake questionnaire was completed by caregivers in which they were asked to describe their child as little overweight, overweight, very overweight or obese. OUTCOME MEASURES: Mean body mass index z score was compared to each parental descriptor. Regression analysis related body mass index z score to birthweight and parental body mass index. RESULTS: Body mass index z score was not related to parental descriptors. Maternal body mass index and child birthweight were predictors of the child's body mass index z score (r2=0.15, p<0.05; and r2=0.11, p<0.05, respectively). Both together produced a better model than either alone (r2=0.23, p<0.05). There was no relationship between paternal and child body mass index z score (p>0.05). CONCLUSIONS: There is a divergence between the parental perception of childhood obesity and the clinical definition that persists even in the context of an explicit referral. Given the significant impact of maternal weight on childhood overweight, education for prevention of overweight youth should encompass prenatal, early childhood and adolescent health maintenance. PMID- 17722670 TI - QT interval dispersion changes according to the vessel involved during percutaneous coronary angioplasty. AB - Increased QT dispersion (QTd) is a noninvasive marker of an electrophysiologic abnormality associated with high mortality in coronary artery disease. The purposes of this study were to measure changes in QTd and ST-segment changes immediately before, during and after intracoronary balloon inflation and to determine whether the coronary artery vessel involved and/or the duration of inflation affect(s) QTd. A total of 45 patients (32 men, 13 women, mean age 58 +/ 11 years) who were referred for elective percutaneous transluminal coronary angioplasty were included. The mean QT interval dispersions for all patients before the inflation, during the balloon inflation at 60 sec and after the balloon deflation at 5 min were 68 +/- 13 ms, 82 +/- 16 ms and 71 +/- 13 ms, respectively. There was no significant difference between baseline and 5 min after deflation. The increase in QTd during the balloon inflation was significant (p<0.01). There was no significant QTd change in patients with left circumflex artery (Cx) lesions during inflation and after deflation compared with baseline. The differences were statistically significant only in patients with left anterior descending (LAD) lesions and right coronary artery (RCA) lesions at 60 sec during balloon inflation (p=0.001 vs. p=0.04). Acute reversible myocardial ischemia induced by balloon inflation causes an increase in QTd limited to the LAD and RCA vessels. Therefore, when using QTd as a marker of myocardial repolarization abnormality due to acute reversible ischemia, the involved coronary artery vessel must be taken into account. PMID- 17722671 TI - Recruiting diverse patients to a breast cancer risk communication trial--waiting rooms can improve access. AB - Low participation among underserved populations in health research constrains progress in public health practices. From 2003 to 2005, Women's Health Clinic patients at the VCU Health System were recruited to a trial investigating breast cancer risk communication. In secondary analyses, we examined dimensions of the recruitment of these diverse women. The sample characteristics (age, insurance, race and previous mammograms) were compared to the overall clinic. Of recruitment attempts for eligible women, 45% consented; of those who declined, the top cited reasons were lack of time (40%) and lack of interest (18%). Of 899 participants, 35% qualified for the indigent care program, compared to 31% of the overall clinic (P<0.001). Forty-five percent of participants were African American, compared to 54% of overall clinic patients (P<0.001). Participants were younger (50 vs. 53 years, P<0.001) than the overall clinic population. Nonrepresentative enrollment of patients in clinical trials is common and could lead to suboptimal applicability of findings. Although there were statistically significant race and age differences between the study sample and the overall population, we demonstrate that waiting room recruitment can engage diverse women in a clinical trial and cancer risk communication. PMID- 17722672 TI - Trends in kidney transplantation rates and disparities. AB - OBJECTIVE: To examine the likelihood of transplantation and trends over time among persons with end-stage renal disease (ESRD) in Wisconsin. METHODS: We examined the influence of patient- and community-level characteristics on the rate of kidney transplantation in Wisconsin among 22,387 patients diagnosed with ESRD between January 1, 1982 and October 30, 2005. We grouped patients by the year of ESRD onset in order to model the change in transplantation rates over time. RESULTS: After multivariate adjustment, all other racial groups were significantly less likely to be transplanted compared with whites, and the racial disparity increased over calendar time. Older patients were less likely to be transplanted in all periods. Higher community income and education level and a greater distance from patients' residence to the nearest dialysis center significantly increased the likelihood of transplantation. Males also had a significantly higher rate of transplantation than females. CONCLUSION: These results demonstrate a growing disparity in transplantation rates by demographic characteristics and a consistent disparity in transplantation by socioeconomic characteristics. Future studies should focus on identifying specific barriers to transplantation among different subpopulations in order to target effective interventions. PMID- 17722673 TI - Dialysis access thrombosis in a family cohort. AB - In 2004, 464,952 individuals were newly diagnosed with chronic renal insufficiency (CRI); 102,356 of those newly diagnosed patients required initiation of dialysis for end-stage renal disease (ESRD). Among the ESRD population, about one third is African American despite the fact that this population represent only about 12% of the total population in the United States (U.S. Renal Data System 2006). Familial aggregation of kidney disease disproportionately affects minorities. This paper describes the detection and management of dialysis access failure due to hypercoagulable states in a genetically related group. We also discuss the implications that associated familial disorders may have on the diagnoses, treatment and survival for this devastating illness. PMID- 17722674 TI - Childhood pyogenic meningitis: clinical and investigative indicators of etiology and outcome. AB - The relevant parameters of 71 consecutive pediatric admissions for pyogenic meningitis at the University of Ilorin Teaching Hospital, Ilorin, Nigeria, were analyzed to identify possible clinical and nonmicrobiologic investigative clues of disease etiology and mortality. Cerebrospinal fluid (CSF) was Gram-smear positive (GSP) in 41 (57.6%) of the 71 cases. Twenty-three (56.1%) had Gram positive cocci (GPC), 14 (34.2%) Gram-negative bacilli (GNB) and three (7.3%) Gram-negative diplococci (GND). The respective mean ages of GPC, GNB and GND cases were 4.49 +/- 5.3, 3.06 +/- 4.8 and 4.47 +/-4.9 years. Streptococcus pneumoniae accounted for 22 (78.6%) of the 28 CSF isolates (p=0.00), Haemophilus influenzae for two (7.1%) cases and Neisseria meningitides in one (3.5%). Anemia was significantly more common among GSP cases (p=0.04), as was convulsion among those with GNB-positive smears (p=0.03) and a bulging fontanelle in the Gram smear-negative category. Otherwise, the prevalence and resolution times of the other clinical parameters were comparable across the etiological categories. There were 30 deaths (42.3%) among which GNB-positive cases had significantly shorter stay (p=0.045). Mortality was significantly higher in those with an abnormal respiratory rhythm at admission (p=0.04), purulent/turbid CSF (p=0.03), CSF protein of >150 mg/dl (p=0.02) and glucose <1 mg/dl (p=0.047). Our findings highlight the inherent limitations of predicting the etiology of pediatric meningitides from the clinical parameters as well as the poor prognostic import of respiratory dysrhythmia and a profoundly deranged CSF protein and glucose. The etiological burden of GPC/S. pneumoniae in childhood meningitides in sub-Saharan Africa, the propensity of GNB/H. influenzae for quick fatality and the need for the relevant preventive vaccines are expounded in the discussion. PMID- 17722675 TI - Diffuse large B-cell lymphoma mimicking advanced basal cell carcinoma. AB - Primary cutaneous B-cell lymphomas (PCBCLs) are made up of a heterogenous group of B-cell lymphoproliferative diseases confined to the skin at the time of diagnosis with no evidence of extracutaneous involvement. With early diagnosis and adequate treatment, PCBCLs as a group has excellent prognosis, with about a 95% survival rate at five years. We report a case of diffuse large B-cell lymphoma (DLBCL) in a 52-year-old woman presenting as a fungating skin ulcer mimicking advanced basal cell carcinoma. Review of available literature showed most studies of PCBCLs being done on Europeans with no universally acceptable system of classification. Clinical findings, diagnostic evaluations and treatment outcomes of PCBCLs are discussed with emphasis on comparison of European Organization for Research and Treatment of Cancer (EORTC) and the World Health Organization (WHO) Classification of Neoplasms of the Hematopoietic and Lymphoid Tissue classification systems. PMID- 17722676 TI - Remembering the patient when rebuilding the Charity Hospital system. PMID- 17722677 TI - Pay-for-performance--financial health disparities and the impact on healthcare disparities. PMID- 17722678 TI - Adenomatous hyperplasia of the gallbladder. AB - Adenomatous hyperplasia of the gallbladder is an uncommon condition, particularly in men. A literature search yields minimal information on this entity, thus suggesting the infrequency of its occurrence. Adenomyomatosis is an entity that closely resembles adenomatous hyperplasia but has hypertrophy of the muscular layer and extensive Rokitansky-Aschoff sinuses. We report the finding of adenomatous hyperplasia in a middle-aged male in the setting of symptomatic cholelithiasis. PMID- 17722679 TI - Partitioning the adoption process to better predict permanency. AB - Under federal outcome standards established by the Adoption and Safe Families Act of 1997, discharges to adoption are expected to occur within 24 months of the most recent removal from home for at least 32% of cases. In the research recounted here, adoption is treated as a process composed of two discrete steps: adoptive placement and adoption finalization. It was hypothesized that the predictors of completion may differ for each step, offering direction for practice and policy. Predictors included child characteristics, maltreatment history, placement history, system variables, and service delivery variables. Children's adoption event history was viewed through five annual entry cohorts, including all children with adoption case plans, rather than the exit cohorts of the federal measure, which includes only adopted children. Over this five-year period, the length of time from removal to adoption finalization decreased significantly, primarily as a result of decreased time from adoption placement to finalization. Child and family characteristics and abuse/neglect history were found to be much more predictive in the analysis of timely adoption placement than of time from placement to finalization. These and other significant predictors suggest strategies for improving timely adoption outcomes. PMID- 17722680 TI - An exploratory study of drug-exposed infants: case substantiation and subsequent child maltreatment. AB - This study explores factors related to drug-exposed infants' case substantiation and subsequent child maltreatment. Child protective services computerized administrative data (from January 1998 to October 2001) were obtained from an urban Nevada county. The data included 457 drug-exposed infant cases. Chi-square, t-test, one-way ANOVA, and logistic regression were used to analyze the data. Results indicate that: (1) drug-exposed infant case substantiation was related to the type of drug exposure and the unit to which the case was assigned, but not to the mother's ethnicity; and (2) subsequent maltreatment among drug-exposed infants was related to the mother's age and prior parental alcohol abuse, but not to the type of drug exposure, nor to the initial drug-exposed infant status of case substantiation. Implications for child welfare practice and research are discussed. PMID- 17722681 TI - Family group decision making and disproportionality in foster care: a case study. AB - Research on the disproportionate number of children of color in the child welfare system suggests that we should focus on key decision points such as investigations, substantiations, and placements to understand how experiences of children vary by race and ethnicity. This article describes one community's efforts to use Family Group Decision Making in placement decisions to reduce disproportionality in foster care by diverting children from regular foster care services and keeping them within their extended families. PMID- 17722682 TI - Characteristics of difficult-to-place youth in state custody: a profile of the Exceptional Care Pilot Project population. AB - This study examines the characteristics of Texas youth designated as 'most difficult to place' recipients of service under the "Exceptional Care Pilot Project" (N = 46). Findings include, among others, high levels of comorbid psychiatric disturbance (> 3 diagnostic groupings), physical (78.3%) and sexual (88%) maltreatment, and placement breakdowns (m = 4.8 therapeutic placements). This initial profile of the population provides a base for helping other states identify and plan for the needs of their most troubled youth. PMID- 17722683 TI - Mental health and behavioral problems of youth in the child welfare system: residential treatment centers compared to therapeutic foster care in the Odyssey Project population. AB - This is the first multisite, prospective study of behavioral and mental health disorders of youth in residential treatment centers (RTC) and therapeutic foster care (TFC), and the first study to compare the two. This study addressed two questions in a sample of 22 agencies in 13 states: (1) how prevalent were emotional and behavioral disorders in the youth admitted to RTCs and TFC?, and (2) were the youth in RTCs significantly more likely to be disturbed than youth served in TFCs? Data were drawn from the Time 1 phase of the longitudinal national "Odyssey Project" developed by the Child Welfare League of America (1995). Measures included an extensive child and family characteristics form (CFC) and the Child Behavior Checklist (CBCL). The results revealed extremely high levels of behavioral and mental health disorders in the sample as a whole, well above the norms for a non-child welfare population. The prevalence of disorder in the RTC population was substantially greater than in the TFC population. PMID- 17722684 TI - Methamphetamine and the changing face of child welfare: practice principles for child welfare workers. AB - Methamphetamine use and production is changing child welfare practice. Methamphetamine is a significant public health threat (National Institute of Justice, 1999) reaching epidemic proportions (Anglin, Burke, Perrochet, Stamper, & Dawud-Nouris, 2000). The manufacturing of methamphetamine is a serious problem for the child welfare system, yet child welfare has not addressed the needs of children living in homes where methamphetamine is manufactured (U.S. Department of Justice, 2002; DOJ, 2003; Altshuler, 2005). This article presents key issues for child welfare workers related to the use, production, and effects of methamphetamine on children and families, and identifies practice principles for child welfare workers in order to ensure safety for victims, parents, and workers themselves. PMID- 17722685 TI - World Suicide Prevention Day--September 10, 2007: "suicide prevention across the life span". PMID- 17722686 TI - Suicide and alcohol psychoses in Belarus 1970-2005. AB - BACKGROUND: The relationship between alcohol and suicide is well documented. The research evidence suggests an important role for a cultural and social context in the alcohol-suicide association. PURPOSE: To estimate the aggregate level effect of alcohol consumption on the suicide rate in Slavic culture. METHOD: Trends in the suicide and alcohol-psychoses morbidity rate in the former Soviet Slavic republic of Belarus from 1970 to 2005 were analyzed employing an ARIMA time series analysis. RESULTS: The results of the analysis suggest a close association between the suicide and alcohol-psychoses morbidity rate. CONCLUSION: This study replicates previous findings that highlighted a close link between alcohol and suicide at the aggregate level. The results of this study also suggest that alcohol is responsible for the fluctuation of the suicide rate in the former Soviet republic of Belarus during the last decades. PMID- 17722687 TI - The relationship between psychological buffers, hopelessness, and suicidal ideation: identification of protective factors. AB - In this study we examined the role of psychological buffers (life satisfaction, self-esteem, perception of family cohesion, and perception of social support) in the development of hopelessness and suicidal ideation. The participants were 314 university students, 71 males and 243 females, who were asked to complete a battery of instruments measuring the psychological buffers mentioned above. The results of a set of hierarchical multiple regression analyses suggested that life satisfaction and self-esteem are independent predictors of lower levels of hopelessness, while perception of social support seems to be the major predictor of lower levels of suicidal ideation independent of depression and hopelessness severity. Thus, hopelessness seems to be minimized by the level of life satisfaction and level of self-esteem exhibited by the individuals, while the key factor to the mitigation of suicidal ideas seems to be perception of social support. PMID- 17722688 TI - Assessment of accuracy of suicide mortality surveillance data in South Africa: investigation in an urban setting. AB - Although it is not a legal requirement in South Africa, medical practitioners determine the manner of injury death for a surveillance system that is currently the only source of epidemiological data on suicide. This study assessed the accuracy of suicide data as recorded in the system using the docket produced from standard medico-legal investigation procedures as the gold standard. It was conducted in one of three cities where the surveillance system had full coverage for the year 2000. In the medico-legal system, one-third of cases could not be tracked, had not been finalized, or had unclear outcomes. For the remaining cases, the sensitivity, specificity, and positive and negative predictive values were generally high, varying somewhat across sex and race groups. Poisoning, jumping, and railway suicides were more likely than other methods to be misclassified, and were more common among females and Whites. The study provides encouraging results regarding the use of medical practitioner expertise for the accurate determination of suicide deaths. However, suicides may still be underestimated in this process given the challenge of tracing disguised suicides and without the careful examination of potential misclassifications of true suicides as unintentional deaths. PMID- 17722689 TI - Suicide and changing values and beliefs in Ireland. AB - This paper addresses some of the generalized theories explaining rising suicide rates in Ireland. The conclusion here is that linking suicide patterns to changing beliefs and values is problematic. Church attendance as well as adherence to traditional values remain high in this country compared to European levels, and variations in beliefs and values, especially rural/urban differences, do not fit with general explanations. Moreover, attitudes to value areas fluctuate in that justification for suicide--which showed an upward trend in the 1980s--was reversed in the 1990s, and this may have resulted from increased public focus and debate. Generalized explanations are unlikely to decipher complex phenomena such as suicidal behavior. Religious belief, if protective in relation to suicide, is unlikely to act alone. Social transformations have a differential impact depending on one's socio-economic positioning, which translates ideas of a general male vulnerability to suicide into focused areas of male distress. PMID- 17722690 TI - The economic cost of suicide in Ireland. AB - OBJECTIVE: To calculate the costs of suicide in Ireland. METHOD: The paper identifies all episodes of suicide in Ireland in 2001 and 2002, and projects the economic costs arising from these episodes over subsequent years. All prices have been converted to 2001 Euros. Both direct and indirect costs were calculated. Indirect costs included both the cost of lost output and human costs. RESULTS: The total cost of suicide is estimated at over Euro 906 million in 2001, and over Euro 835 million in 2002 (in 2001 prices). This is equivalent to a little under 1% of the gross national product in Ireland for those years. CONCLUSIONS: The results show that investment in health education and health promotion can be justified on the basis of the costs associated with suicide in Ireland. These costs fall on individuals, families, and society. The huge human cost of suffering associated with suicide can also be prevented through appropriate intervention to prevent death occurring. It is important that any suicide prevention strategy should include an evaluative framework to ensure that investment occurs in the areas most likely to generate the highest returns in term of suicides prevented and lives saved. PMID- 17722691 TI - Unemployment and suicidal behavior in a New Zealand birth cohort: a fixed effects regression analysis. AB - This study examined the association between exposure to unemployment and suicidal behaviors (suicidal ideation and attempted suicide) in a birth cohort of New Zealand young adults using fixed-effects logistic and Poisson regression models. Data were gathered on unemployment and suicidal behaviors at annual periods from ages 16-25 years. At all ages increasing exposure to unemployment was associated with increased risks of suicidal ideation (p < .0001) and number of suicide attempts (p < .0001). Following adjustment for fixed effects and time-dynamic covariates, associations between unemployment and suicidal ideation reduced to marginal significance (p < .10), while the association between unemployment and suicide attempts was not statistically significant (p > .10). After adjustment, those experiencing 6 or more months of unemployment in a given year had odds of suicidal ideation that were 1.43 (95% CI: .96 to 2.16) times higher, and rates of suicide attempts that were 1.72 (95% CI: .89 to 3.32) times higher, than those who were not exposed to unemployment. Although unemployment was associated with moderate increases in risks of suicidal behaviors, much of this association was explained by confounding factors. PMID- 17722692 TI - The content of suicide notes from attempters and completers. AB - A study of the content of suicide notes from attempted suicides and completed suicides was conducted using the Linguistic Inquiry and Word Count (LIWC) text analysis program. Notes from completed suicides had fewer metaphysical references, more future tense verbs, more social references (to others) and more positive emotions than did the notes from attempted suicides. The implications of these results were discussed. PMID- 17722693 TI - Distinct biphasic mRNA changes in response to Asian soybean rust infection. AB - Asian soybean rust (ASR), caused by Phakopsora pachyrhizi, is now established in all major soybean-producing countries. Currently, there is little information about the molecular basis of ASR-soybean interactions, which will be needed to assist future efforts to develop effective resistance. Toward this end, abundance changes of soybean mRNAs were measured over a 7-day ASR infection time course in mock-inoculated and infected leaves of a soybean accession (PI230970) carrying the Rpp2 resistance gene and a susceptible genotype (Embrapa-48). The expression profiles of differentially expressed genes (ASR-infected compared with the mock inoculated control) revealed a biphasic response to ASR in each genotype. Within the first 12 h after inoculation (hai), which corresponds to fungal germination and penetration of the epidermal cells, differential gene expression changes were evident in both genotypes. mRNA expression of these genes mostly returned to levels found in mock-inoculated plants by 24 hai. In the susceptible genotype, gene expression remained unaffected by rust infection until 96 hai, a time period when rapid fungal growth began. In contrast, gene expression in the resistant genotype diverged from the mock-inoculated control earlier, at 72 h, demonstrating that Rpp2-mediated defenses were initiated prior to this time. These data suggest that ASR initially induces a nonspecific response that is transient or is suppressed when early steps in colonization are completed in both soybean genotypes. The race-specific resistance phenotype of Rpp2 is manifested in massive gene expression changes after the initial response prior to the onset of rapid fungal growth that occurs in the susceptible genotype. PMID- 17722694 TI - Identification of 118 Arabidopsis transcription factor and 30 ubiquitin-ligase genes responding to chitin, a plant-defense elicitor. AB - Chitin, found in the cell walls of true fungi and the exoskeleton of insects and nematodes, is a well-established elicitor of plant defense responses. In this study, we analyzed the expression patterns of Arabidopsis thaliana transcription factor (TF) and ubiquitin-ligase genes in response to purified chitooctaose at different treatment times (15, 30, 60, 90, and 120 min after treatment), using both quantitative polymerase chain reaction and the Affymetrix Arabidopsis whole genome array. A total of 118 TF genes and 30 ubiquitin-ligase genes were responsive to the chitin treatment. Among these genes, members from the following four TF families were overrepresented: APETALA2/ethylene-reponsive element binding proteins (27), C2H2 zinc finger proteins (14), MYB domain-containing proteins (11), and WRKY domain transcription factors (14). Transcript variants from a few of these genes were found to respond differentially to chitin, suggesting transcript-specific regulation of these TF genes. PMID- 17722695 TI - A novel nuclear protein interacts with the symbiotic DMI3 calcium- and calmodulin dependent protein kinase of Medicago truncatula. AB - Many higher plants establish symbiotic relationships with arbuscular mycorrhizal (AM) fungi that improve their ability to acquire nutrients from the soil. In addition to establishing AM symbiosis, legumes also enter into a nitrogen-fixing symbiosis with bacteria known as rhizobia that results in the formation of root nodules. Several genes involved in the perception and transduction of bacterial symbiotic signals named "Nod factors" have been cloned recently in model legumes through forward genetic approaches. Among them, DMI3 (Doesn't Make Infections 3) is a calcium- and calmodulin-dependent kinase required for the establishment of both nodulation and AM symbiosis. We have identified, by a yeast two-hybrid system, a novel protein interacting with DMI3 named IPD3 (Interacting Protein of DMI3). IPD3 is predicted to interact with DMI3 through a C-terminal coiled-coil domain. Chimeric IPD3::GFP is localized to the nucleus of transformed Medicago truncatula root cells, in which split yellow fluorescent protein assays suggest that IPD3 and DMI3 physically interact in Nicotiana benthamiana. Like DMI3, IPD3 is extremely well conserved among the angiosperms and is absent from Arabidopsis. Despite this high level of conservation, none of the homologous proteins have a demonstrated biological or biochemical function. This work provides the first evidence of the involvement of IPD3 in a nuclear interaction with DMI3. PMID- 17722696 TI - Disruption of a maize 9-lipoxygenase results in increased resistance to fungal pathogens and reduced levels of contamination with mycotoxin fumonisin. AB - Plant oxylipins, produced via the lipoxygenase (LOX) pathway, function as signals in defense and development. In fungi, oxylipins are potent regulators of mycotoxin biosynthesis and sporogenesis. Previous studies showed that plant 9-LOX derived fatty acid hydroperoxides induce conidiation and mycotoxin production. Here, we tested the hypothesis that oxylipins produced by the maize 9-LOX pathway are required by pathogens to produce spores and mycotoxins and to successfully colonize the host. Maize mutants were generated in which the function of a 9-LOX gene, ZmLOX3, was abolished by an insertion of a Mutator transposon in its coding sequence, which resulted in reduced levels of several 9-LOX-derived hydroperoxides. Supporting our hypothesis, conidiation and production of the mycotoxin fumonisin B1 by Fusarium verticillioides were drastically reduced in kernels of the lox3 mutants compared with near-isogenic wild types. Similarly, conidia production and disease severity of anthracnose leaf blight caused by Colletotrichum graminicola were significantly reduced in the lox3 mutants. Moreover, lox3 mutants displayed increased resistance to southern leaf blight caused by Cochliobolus heterostrophus and stalk rots caused by both F. verticillioides and C. graminicola. These data strongly suggest that oxylipin metabolism mediated by a specific plant 9-LOX isoform is required for fungal pathogenesis, including disease development and production of spores and mycotoxins. PMID- 17722697 TI - All five host-range variants of Xanthomonas citri carry one pthA homolog with 17.5 repeats that determines pathogenicity on citrus, but none determine host range variation. AB - Citrus canker disease is caused by five groups of Xanthomonas citri strains that are distinguished primarily by host range: three from Asia (A, A*, and A(w)) and two that form a phylogenetically distinct clade and originated in South America (B and C). Every X. citri strain carries multiple DNA fragments that hybridize with pthA, which is essential for the pathogenicity of wide-host-range X. citri group A strain 3213. DNA fragments that hybridized with pthA were cloned from a representative strain from all five groups. Each strain carried one and only one pthA homolog that functionally complemented a knockout mutation of pthA in 3213. Every complementing homolog was of identical size to pthA and carried 17.5 nearly identical, direct tandem repeats, including three new genes from narrow-host range groups C (pthC), A(w) (pthAW), and A* (pthA*). Every noncomplementing paralog was of a different size; one of these was sequenced from group A* (pthA* 2) and was found to have an intact promoter and full-length reading frame but with 15.5 repeats. None of the complementing homologs nor any of the noncomplementing paralogs conferred avirulence to 3213 on grapefruit or suppressed avirulence of a group A* strain on grapefruit. A knockout mutation of pthC in a group C strain resulted in loss of pathogenicity on lime, but the strain was unaffected in ability to elicit an HR on grapefruit. This pthC- mutant was fully complemented by pthA, pthB, or pthC. Analysis of the predicted amino acid sequences of all functional pthA homologs and nonfunctional paralogs indicated that the specific sequence of the 17th repeat may be essential for pathogenicity of X. citri on citrus. PMID- 17722698 TI - Type 2A phosphoprotein phosphatase is required for asexual development and pathogenesis of Sclerotinia sclerotiorum. AB - Sclerotinia sclerotiorum is a necrotrophic, omnivorous plant pathogen with worldwide distribution. Sclerotia of S. sclerotiorum are pigmented, multihyphal structures that play a central role in the life and infection cycles of this pathogen. Plant infection depends on the formation of melanin-rich infection cushions, and secretion of hydrolytic enzymes and oxalic acid. Type 2A Ser/Thr phosphatases (PP2As) are involved in the regulation of a variety of cellular process. In the presence of cantharidin, a PP2A-specific inhibitor, hyphal elongation and sclerotia numbers were impaired whereas sclerotial size increased. We partially inactivated PP2A by antisense expression of the gene (pph1) encoding the PP2A catalytic subunit. When antisense expression was induced, almost complete cessation of fungal growth was observed, indicative of a crucial role for PP2A in fungal growth. RNAi-based gene silencing was employed to alter the expression of the 55-kDa R2 (B regulatory subunit). Isolates in which rgb1 RNA levels were decreased were slow growing, but viable. Melanin biosynthesis, infection-cushion production, and pathogenesis were significantly impaired in the rgb1 mutants, yet theses mutants were pathogenic on wounded leaves. Reduced ERK (extracellular signal-regulated kinases)-like mitogen-activated protein kinase (MAPK) function conferred a reduction in NADPH oxidase and PP2A activity levels, suggesting a functional link between MAPK, reactive oxygen species, and PP2A activity in S. sclerotiorum. PMID- 17722699 TI - The phytotoxin coronatine contributes to pathogen fitness and is required for suppression of salicylic acid accumulation in tomato inoculated with Pseudomonas syringae pv. tomato DC3000. AB - The roles of the phytotoxin coronatine (COR) and salicylic acid (SA)-mediated defenses in the interaction of Pseudomonas syringae pv. tomato DC3000 and tomato (Solanum lycopersicum) were investigated. Unlike findings reported for Arabidopsis thaliana, DC3000 mutants impaired for production of COR or one of its components, coronafacic acid (CFA) or coronamic acid (CMA), induced distinctly different disease lesion phenotypes in tomato. Tomato plants inoculated with the CFA- CMA- mutant DB29 showed elevated transcript levels of SlICS, which encodes isochorismate synthase, an enzyme involved in SA biosynthesis in S. lycopersicum. Furthermore, expression of genes encoding SA-mediated defense proteins were elevated in DB29-inoculated plants compared with plants inoculated with DC3000, suggesting that COR suppresses SlICS-mediated SA responses. Sequence analysis of SlICS revealed that it encodes a protein that is 55 and 59.6% identical to the A. thaliana ICS-encoded proteins AtICS1 and AtICS2, respectively. Tomato plants silenced for SlICS were hypersusceptible to DC3000 and accumulated lower levels of SA after infection with DC3000 compared with inoculated wild-type tomato plants. Unlike what has been shown for A. thaliana, the COR- mutant DB29 was impaired for persistence in SlICS-silenced tomato plants; thus, COR has additional roles in virulence that are SA independent and important in the latter stages of disease development. In summary, the infection assays, metabolic profiling, and gene expression results described in this study indicate that the intact COR molecule is required for both suppression of SA-mediated defense responses and full disease symptom development in tomato. PMID- 17722700 TI - Expression of the membrane-associated resistance protein RPW8 enhances basal defense against biotrophic pathogens. AB - The powdery mildew resistance genes RPW8.1 and RPW8.2 from Arabidopsis differ from the other isolated plant resistance (R) genes in their predicted protein domains and their resistance spectrum. The two homologous RPW8 genes encode small proteins featuring a predicted amino-terminal transmembrane anchor domain and a coiled-coil domain and confer resistance to a broad spectrum of powdery mildews. Here, we show that Arabidopsis plants expressing the RPW8 genes have enhanced resistance to another biotrophic pathogen, Hyaloperonospora parasitica, raising the possibility that the RPW8 genes may function to enhance salicylic-acid dependent basal defenses, rather than as powdery-mildew-specific R genes. When overexpressed from their native promoters, the RPW8 genes confer enhanced resistance to the Cauliflower mosaic virus, but render plants more susceptible to the necrotrophic fungal pathogens Alternaria and Botrytis spp. Furthermore, we show that the RPW8 proteins appear to be localized to the endomembrane system, overlapping with the endoplasmic reticulum-associated small GTPase SAR1, and accumulate to higher levels in response to application of exogenous salicylic acid, one of the signaling molecules of plant defense. PMID- 17722701 TI - Role of the transcriptional activator xlnR of Fusarium oxysporum in regulation of xylanase genes and virulence. AB - Fungal infection of plants involves degradation of the host cell wall through the action of lytic enzymes secreted by the pathogen. The role of these enzymes in virulence is difficult to determine due to their functional redundancy and, therefore, remains controversial. Here, we have studied XlnR, a zinc-finger transcription factor from the vascular wilt pathogen Fusarium oxysporum that is orthologous to the major transcriptional activator of xylanase genes in Aspergillus spp. Transcription of the xlnR gene was activated by inducing carbon sources such as oat spelt xylan (OSX) and repressed by glucose. Targeted knockout of xlnR in F. oxysporum resulted in lack of transcriptional activation of structural xylanase genes, both in culture and during infection of tomato plants, as well as in dramatically reduced extracellular xylanase activity. By contrast, overexpression of xlnR under the control of the Aspergillus nidulans gpdA promoter did not significantly increase xylanase activity, suggesting that XlnR is regulated not only at the transcriptional but also at the post-translational level. The deltaxlnR mutants were still fully virulent on tomato plants. Thus, XlnR, the major transcriptional activator of xylanase genes, is not an essential virulence determinant in F. oxysporum. PMID- 17722702 TI - Differential effects of combined N sources on early steps of the Nod factor dependent transduction pathway in Lotus japonicus. AB - The development of nitrogen-fixing nodules in legumes is induced by perception of lipochitin-oligosaccharide signals secreted by a bacterial symbiont. Nitrogen (N) starvation is a prerequisite for the formation, development, and function of root nodules, and high levels of combined N in the form of nitrate or ammonium can completely abolish nodule formation. We distinguished between nitrate and ammonium inhibitory effects by identifying when and where these combined N sources interfere with the Nod-factor-induced pathway. Furthermore, we present a small-scale analysis of the expression profile, under different N conditions, of recently identified genes involved in the Nod-factor-induced pathway. In the presence of high levels of nitrate or ammonium, the NIN gene fails to be induced 24 h after the addition of Nod factor compared with plants grown under N-free conditions. This induction is restored in the hypernodulating nitrate-tolerant har1-3 mutant only in the presence of 10 and 20 mM KNO3. These results were confirmed in Lotus plants inoculated with Mesorhizobium loti. NIN plays a key role in the nodule organogenesis program and its downregulation may represent a crucial event in the nitrate-dependent pathway leading to the inhibition of nodule organogenesis. PMID- 17722704 TI - Proton pump inhibitors and the kidney: critical review. AB - Proton pump inhibitors (PPIs) are widely prescribed to treat a number of gastrointestinal disorders due to excessive acid production. While effective and safe, adverse renal effects have been described. Most concerning is the ever increasing number of cases of acute interstitial nephritis (AIN) associated with PPI therapy. It appears to be a class effect as all PPIs have been documented to cause AIN. Several adverse drug event registries now note PPIs as the most common cause of drug-induced AIN. While most patients recover kidney function, many are left with some level of chronic kidney disease. Hyponatremia is an extremely rare complication and is thought to result from inappropriate ADH secretion. Interactions with calcineurin inhibitors may occur with certain PPIs when used in susceptible patients, particularly those with polymorphisms in the cytochrome P450-2C19 enzyme gene. This paper will critically review the effect of PPIs on the kidney. PMID- 17722703 TI - Comparative expression profiling of Nicotiana benthamiana leaves systemically infected with three fruit tree viruses. AB - Plant viruses cause a wide array of disease symptoms and cytopathic effects. Although some of these changes are virus specific, many appear to be common even among diverse viruses. Currently, little is known about the underlying molecular determinants. To identify gene expression changes that are concomitant with virus symptoms, we performed comparative expression profiling experiments on Nicotiana benthamiana leaves infected with one of three different fruit tree viruses that produce distinct symptoms: Plum pox potyvirus (PPV; leaf distortion and mosaic), Tomato ringspot nepovirus (ToRSV; tissue necrosis and general chlorosis), and Prunus necrotic ringspot ilarvirus (PNRSV; subtle chlorotic mottling). The numbers of statistically significant genes identified were consistent with the severity of the observed symptoms: 1,082 (ToRSV), 744 (PPV), and 89 (PNRSV). In all, 56% of the gene expression changes found in PPV-infected leaves also were altered by ToRSV, 87% of which changed in the same direction. Both PPV- and ToRSV infected leaves showed widespread repression of genes associated with plastid functions. PPV uniquely induced the expression of large numbers of cytosolic ribosomal genes whereas ToRSV repressed the expression of plastidic ribosomal genes. How these and other observed expression changes might be associated with symptom development are discussed. PMID- 17722705 TI - Desmin as a marker of proteinuria in early stages of membranous nephropathy in elderly patients. AB - AIMS AND METHOD: Idiopathic membranous nephropathy (IMN) is the most common cause of nephrotic syndrome in adults worldwide. Many patients with IMN are elderly, but little is known about the relationship regarding the morphological stage determined by electron microscopy (EM), the amount of proteinuria, and the expression of glomerular podocyte markers such as desmin and nephrin in nephrotic glomeruli in IMN. We studied 59 patients with histopathologically proven IMN. We compared the clinical features, EM stage classification, and the immunohistochemical features of glomerular expression of podocyte markers, including desmin and nephrin, between older (age > or = 60 years) and younger (age < 60 years) patients. We also investigated these parameters in patients with minimal-change nephrotic syndrome (MCNS), minor glomerular abnormalities (MGA), and normal kidneys as age-matched controls. RESULTS: Prevalence of nephrotic syndrome was significantly higher in the older (52.9%) than the younger group (20.0%) of IMN. The level of proteinuria was higher in early stages (Stages I + II) than in late stages (Stages III + IV) in IMN. The glomerular expression of desmin in podocytes was significantly higher in IMN as compared to MCNS, MGA, or age-matched controls. Desmin expression was significantly increased in earlier EM stages (Stages I + II) and in higher proteinuric group (daily proteinuria > or = 1 g) of older patients with IMN. Reciprocally, the reduced expression of nephrin was associated with the early EM stages (Stages I + II) of patients with IMN. CONCLUSIONS: We conclude that the expression of desmin in podocytes is upregulated in patients with IMN as compared to other glomerular diseases including MCNS or MGA, or to controls. In elderly patients with IMN, desmin expression was associated with early EM stages and heavy proteinuria, which may reflect phenotypic alteration of the podocyte. PMID- 17722706 TI - Association of diabetic retinopathy and renal function in patients with types 1 and 2 diabetes mellitus. AB - AIMS: It takes years for microvascular complications in diabetes mellitus such as diabetic retinopathy (RP) and nephropathy (NP) to develop. Since retinal and renal vessels are exposed to the diabetic milieu, it is often assumed that progression of diabetic RP and NP occurs at the same time. However, smaller studies have demonstrated that this may not always be the case. The present study was undertaken to correlate diabetic retinopathy with parameters of renal function in a large ambulatory collective of patients with Types 1 and 2 diabetes. METHODS: The study design was cross-sectional. Ambulatory patients from a large university out-patient clinic were studied (323 patients with Type 1, 906 patients with Type 2 diabetes). RP status was obtained through retinal photography by an experienced ophthalmologist and was grouped into no RP, RP Stages 1-3, or blind. Retinal pathology was correlated with clinical parameters of renal function (proteinuria, estimated glomerular filtration rate according to the MDRD formula, presence of urinary sediment abnormalities, hypertension). RESULTS: No patient showed urinary sediment abnormalities (e.g. presence of hematuria or acanthocytes) or increased urinary excretion of immunoglobulin light chains suggesting the absence of other nondiabetic renal diseases. The majority of Type 1 diabetes patients with macroalbuminuria (> or = 200 mg/l) had some signs of RP independent of the presence of hypertension. There was a correlation between RP and microalbuminuria (r = 0.164, p < 0.01). In contrast, up to 47.5% of the hypertensive patients with Type 2 diabetes and overt proteinuria had no signs of RP. There was also discordance of microalbuminuria and RP in patients with Type 2 diabetes. Stratification according to K/DOQI States 2-5 (MDRD formula) showed that the majority of patients with Type 1 diabetes in States 3-5 had signs of RP, albeit the absolute number of patients in these K/DOQI stages was very small. In contrast, up to 40% of dialysis-dependent Type 2 diabetics (K/DOQI State 5) showed no evidence of RP. CONCLUSIONS: This study revealed that many patients with Type 2 diabetes and renal abnormalities (proteinuria and/or renal insufficiency) showed, in contrast to Type 1 diabetics, no signs of RP. Our study was, however, limited by the lack of renal biopsies. Although urinary sediment analysis was normal in these patients, other causes for renal insufficiency (e.g. vascular nephropathy), especially in Type 2 diabetics, cannot be excluded. Nevertheless, we believe that absence of RP in patients with Type 2 diabetes does not imply that renal abnormalities including diabetic nephropathy, are also absent. It is recommended that these patients undergo renal biopsy. PMID- 17722707 TI - Mineral metabolism influences pulse pressure increase provoked by chronic kidney disease. AB - BACKGROUND: Pulse pressure (PP) increase has been associated with hypertension, ageing and chronic kidney disease. Although hyperparathyroidism and phosphate imbalance have been suspect in PP increase in hemodialysis patients, the link between these parameters and pulse pressure, in renal disease before dialysis, has not been established. METHODS AND PATIENTS: 1966 chronic kidney disease (CKD) patients. STATISTICS: ANOVA, Student's t-and Chi-square, rank correlations (Spearman) and multivariate analysis, with PP as the dependent variable, while adjusting for other covariables. RESULTS: There was an increase of pulse pressure parallel to renal function deterioration, and a significant influence of age, diabetes, hypertension, phosphate and PTH on pulse pressure in the whole population, as well as in patients with glomerular filtration rate < 60 ml/min. The impact of phosphate was particularly high after the age of 50. CONCLUSION: PP increase present in renal disease patients might be primarily due to the underlying mineral metabolism disturbances. PMID- 17722708 TI - Effect of famotidine and lansoprazole on serum phosphorus levels in hemodialysis patients on calcium carbonate therapy. AB - AIMS: Histamine H2 receptor antagonists (HRA) or proton pump inhibitors (PPI) are frequently administered to patients on hemodialysis, because their intestinal mucosa is fragile. Although three studies have indicated that concomitant HRA administration causes a decrease in the binding of phosphate by calcium carbonate, the HRA doses tested in these studies were 2-4 times higher than the recommended dose for hemodialysis patients. In addition, it remains unclear whether PPI therapy affects serum phosphate levels in hemodialysis patients taking calcium carbonate. Accordingly, the aim of this study was to evaluate the influence of lansoprazole and the recommended dose of famotidine on serum phosphate and calcium levels in hemodialysis patients. METHODS: The study included 115 hemodialysis patients who were taking calcium carbonate and who were also treated with either famotidine (10 mg/day) or lansoprazole (30 mg/day). Changes of the mean serum phosphate and calcium levels over 2 months before and after the start of famotidine or lansoprazole therapy were compared. The same parameters were also compared when famotidine was switched to lansoprazole. RESULTS: The mean serum phosphate level increased significantly after administration of either famotidine or lansoprazole (by 6.6 +/- 21.9% or 13.0 +/- 26.3%, p = 0.032 and p = 0.029, respectively). The mean serum calcium level was unchanged after administration of famotidine, but showed a significant decrease after administration of lansoprazole (by 3.44 +/- 7.73%, p = 0.013). Therefore, the calcium x phosphorus product was significantly increased by administration of famotidine, but not by administration of lansoprazole (6.68 +/- 23.37% and 8.73 +/- 27.41%, p = 0.046 and p = 0.251, respectively). When famotidine was switched to lansoprazole, the serum phosophate level did not change, but serum calcium decreased significantly by 3.8 +/- 13.0% (p = 0.0006). CONCLUSION: Not only administration of 20 mg/ day of famotidine as previously reported, but also 10 mg/day of this drug (the recommended dose for hemodialysis patients) caused a significant increase of serum phosphate in patients taking calcium carbonate. PPIs have been reported to show no effect on the serum phosphate level, but 30 mg/day of lansoprazole also caused a significant increase of serum phosphate in patients taking calcium carbonate. PMID- 17722709 TI - Remission of nephrotic membranous glomerulonephritis after high-dose trimethoprim sulfamethoxazole treatment for pneumocystis jiroveci pneumonia. AB - We report an unusual case of nephrotic syndrome due to membranous glomerulonephritis that responded to high-dose trimethoprim-sulfamethoxazole (TMP SMX) treatment. A 52-year-old man presented with nephrotic syndrome and was diagnosed to have idiopathic membranous glomerulonephritis. At the time of diagnosis, his serum creatinine level was 1.2 mg/dl and daily urine protein excretion was 7.45 g. The patient was initially treated with angiotensin converting enzyme inhibitor and diuretics. After a 6-month period, the patient remained symptomatic. Therefore, immunosuppressive therapy with a 6-month course of alternating corticosteroids with cyclophosphamide was commenced. Unfortunately, as a sequel of the immunocompromised state, the patient acquired severe pneumonia due to Pneumocystis jiroveci infection when he was on the fourth month of immunosuppressive therapy. At this time, he still had nephrotic range proteinuria and hypoalbuminemia. Because of the risk of aggravating infection, immunosuppressive agents were discontinued. A 14-day course of intravenous high dose TMP-SMX therapy was given for the treatment of Pneumocystis jiroveci pneumonia. With this medication, not only the pneumonia was cured, but also a sustained remission of the nephrotic syndrome occurred. This case suggests a possible therapeutic role of high-dose TMP-SMX in membranous glomerulonephritis. We will discuss the possible mechanism. PMID- 17722710 TI - A pediatric occurrence of crescentic glomerulonephritis associated with antineutrophil cytoplasmic antibodies and mesangial IgA deposits. AB - Antineutrophil cytoplasmic antibody-(ANCA) associated glomerulonephritis usually shows histopathologic features of pauciimmune crescentic glomerulonephritis and occurs late in life. We report a 14-year-old Japanese girl presenting with proteinuria, hematuria and mildly elevated serum creatinine. A renal biopsy specimen demonstrated crescentic glomerulonephritis, immunofluorescence showed mesangial IgA staining. Electron microscopic examination disclosed paramesangial deposits. Serum ANCA against myeloperoxidase (MPO) were detected at high titers. Myeloperoxidase-ANCA-related nephritis accompanied by IgA nephropathy is considered rare in childhood and teen years. Yet, if ANCA assays and detailed electron microscopic examination of renal specimens were performed routinely in patients with rapidly progressive glomerulonephritis, the diagnosis might be more frequent in young patients. PMID- 17722711 TI - Hyperammonemia in distal renal tubular acidosis: is it more common than we think? AB - The hyperammonemia in distal renal tubular acidosis, previously only described in two cases, is considered an unusual occurrence. After the report published in 2005, we observed plasma ammonia levels above normal range during metabolic decompensation in two other consecutive pediatric patients suffering from distal renal tubular acidosis. The ammonia plasma levels returned to normal range after treatment with sodium bicarbonate and potassium salt. In distal renal tubular acidosis, hyperammonemia is probably the result of an imbalance between the increased ammonia synthesis, in response to metabolic acidosis, and the impaired ammonia excretion, typical of distal renal tubular acidosis. According to this physiopathological mechanism, our observation shows that hyperammonemia is not an uncommon finding in distal renal tubular acidosis, and should be included among differential diagnosis of hyperammonemia in infants and children. PMID- 17722712 TI - Analgesic nephropathy selectively affecting a unilateral non-functioning hypoplastic kidney. AB - Analgesic nephropathy results from chronic abuse of non-narcotic analgesics, most frequently with the use of phenacetin and mixed analgesic preparations. Renal papillary necrosis and chronic interstitial nephritis with progressive scarring are characteristic of the histopathology of analgesic nephropathy. Typically, papillary necrosis in these patients is bilateral and affects almost all renal papillae. This report describes a case of severe analgesic nephropathy that discriminantly affected a unilateral non-functioning kidney and spared the contralateral normally developed kidney. The patient herein consumed therapeutic doses of acetaminophen and naproxen daily and for several years. We estimated the cumulative doses of acetaminophen and naproxen used by the patient during that period to be approximately 1.0 and 0.4 kg, respectively. The cumulative dose of acetaminophen is at the threshold of doses that were traditionally associated with an increased risk for end-stage kidney failure. Simultaneous intake of both analgesics could have had a synergetic adverse effect on renal function. This case also demonstrates that preexisting renal insufficiency is prerequisite to the development of analgesic nephropathy. Conversely, kidneys with normal function are resistant to the chronic nephrotoxicity associated with habitual analgesic use. PMID- 17722713 TI - Leukocytapheresis (LCAP) for the treatment of rheumatoid arthritis on a maintenance hemodialysis patient. AB - A 57-year-old-woman, who was treated with regular maintenance hemodialysis (HD), newly contracted rheumatoid arthritis (RA). Oral predonisolone was effective for alleviating her arthralgia but the RA activity became steroid-dependent. For treatment of poorly controlled synovitis leukocytapheresis (LCAP) showed excellent efficacy in the treatment of her joint pain. No serious adverse effects were observed. Serological markers such as CRP, serum amyloid A, matrix metalloproteinase 3 and peripheral blood lymphocyte count fluctuated with her clinical symptoms. We recommend LCAP as candidate therapy for steroid-dependent patients with RA who are on maintenance HD. PMID- 17722714 TI - Successful treatment of fulminant encapsulating peritoneal sclerosis following fungal peritonitis with tamoxifen. AB - Encapsulating peritoneal sclerosis remains a serious complication of peritoneal dialysis. Prolonged duration on dialysis and severe episodes of peritonitis are the two most important risk factors for developing the condition. Here we describe a patient who developed a fulminant form of encapsulating peritoneal sclerosis soon after suffering from an episode of fungal peritonitis. There was clinical evidence of ongoing inflammation and gross malnutrition. Signs of chronic intestinal stasis were present on radiological imaging. There was concern in this situation that symptoms could partly relate to ongoing peritoneal sepsis, which could be worsened by immunosuppressives such as steroids. Tamoxifen was used without steroids in our patient with prompt resolution of stasis symptoms and withdrawal of artificial nutrition support. To our knowledge tamoxifen has never been previously used alone, in this scenario. We propose that tamoxifen might be a safer alternative to use in this clinical setting where there is concern about presence of ongoing sepsis, than corticosteroids and immunosuppressive agents. PMID- 17722715 TI - Decreased mineral metabolism parameters (magnesium and phosphate) and elevated pulse pressure in hypertension. PMID- 17722716 TI - Comment on FK 506 analysis. PMID- 17722717 TI - The judgement of Solomon and journal status. PMID- 17722719 TI - A survey of horse owners in Great Britain regarding horses in their care. Part 1: Horse demographic characteristics and management. AB - REASONS FOR PERFORMING STUDY: Information is scarce as to how horses are kept and managed in the general horse population of Great Britain. OBJECTIVES: To characterise the demographics of horses in Great Britain and assess their care (with particular reference to the respiratory system). METHODS: Horse owners were surveyed using a self-administered postal questionnaire. These owners were selected randomly, following geographical stratification, using 2-stage cluster sampling of veterinary practices and their clients. RESULTS: The overall response proportion to the survey was 68.2%. An investigation of nonresponse bias detected minimal differences between responders and nonresponders. A summary of the demographic characteristics, feeding and management of horses in a sample of the general population of Great Britain is presented. CONCLUSIONS AND POTENTIAL RELEVANCE: Horses are kept under a great variety of conditions with some potentially exposed to high concentrations of organic dusts associated with stabling. This information is relevant to their health and welfare. PMID- 17722718 TI - Exercise-induced pulmonary haemorrhage (EIPH): mechanistic bases and therapeutic interventions. PMID- 17722720 TI - A survey of horse owners in Great Britain regarding horses in their care. Part 2: Risk factors for recurrent airway obstruction. AB - REASONS FOR PERFORMING STUDY: Recurrent airway obstruction (RAO) is a commonly encountered respiratory condition of horses. Despite this, the epidemiology of this predominately manageable and reversible disease in Great Britain has been largely ignored. OBJECTIVES: To estimate the prevalence of RAO in the general horse population of Great Britain and to investigate possible risk factors for RAO associated with management or early life. METHODS: Horse owners were surveyed using a self-administered postal questionnaire that contained a risk-screening questionnaire (RSQ) designed to identify horses with RAO. These owners were randomly selected, following geographical stratification, using 2-stage cluster sampling of veterinary practices and their clients. Multilevel, multivariable logistic regression models were used to investigate risk factors for RAO in the selected horse population. RESULTS: The estimated true prevalence of RAO in the selected horse population was 14.0% (95%CI 10.7-17.4%). Risk factors for RAO identified in a general horse management logistic regression model included increasing age and exposure to an urbanised environment. Recurrent airway obstruction has long been associated with mature horses while the association with an urbanised environment could be related to different management practices in these areas or possibly air pollution could be involved. The second model associated exposure to hay and respiratory infection in early life with a horse having RAO in later life. Challenges to the respiratory system in early life may be involved in the development of this disease. CONCLUSIONS AND POTENTIAL RELEVANCE: Recurrent airway obstruction is a significant health problem in the horse population of Great Britain. This form of epidemiological investigation highlights potential risk factors for the disease. PMID- 17722722 TI - Does clinical experience make up for failure to keep up to date? PMID- 17722721 TI - Equine idiopathic cheek teeth fractures. Part 1: Pathological studies on 35 fractured cheek teeth. AB - REASONS FOR PERFORMING STUDY: There is little published information on the pathology of idiopathic fractures of cheek teeth (CT). OBJECTIVES: To perform pathological examinations on equine CT with idiopathic fractures in order to establish fracture patterns and to gain information on their aetiopathogenesis. HYPOTHESIS: Gross and histological examination of CT with idiopathic fractures, including measurements of dentinal thickness, will provide information on fracture patterns, and on the duration and aetiopathogenesis of these fractures. METHODS: Of 35 CT with idiopathic fractures that were examined to determine their fracture patterns, 20 underwent gross, histological and ultrastructural examinations, including dentinal thickness measurements, with the latter compared to dentinal measurements of dental age and Triadan position matched control CT, to help determine the duration of any pre-existing endodontic disease. RESULTS: The fracture planes involved the pulp chambers in 30 out of 35 CT examined, and ran through coalesced, carious infundibula in the other 5 (maxillary) CT. The maxillary CT, particularly the Triadan 09 position were preferentially affected. The most common fracture plane, which was termed a maxillary buccal slab fracture, occurred through the 2 lateral (1st and 2nd) pulp chambers of maxillary CT and usually involved only the clinical crown. Buccal slab fractures of mandibular CT (through 4th and 5th pulp chambers) and midline sagittal fractures through the infundibula (of maxillary CT) were the next most common fracture patterns. Reduced dentinal thickness (probably indicating prior pathological changes in the fractured CT) was present in 25% of fractured CT. CONCLUSIONS: Most idiopathic equine CT fractures involve the pulp chambers, especially those on the buccal aspect of both upper and lower CT. No predisposition to fracture was found in the majority of affected CT that appeared to have a normal endodontic appearance prior to development of fractures through their pulp chambers. The remaining idiopathic CT fractures were caused by advanced infundibular caries. POTENTIAL RELEVANCE: All CT with idiopathic fractures are all at risk of pulpar or even apical infection. PMID- 17722723 TI - Equine idiopathic cheek teeth fractures: part 2: a practice-based survey of 147 affected horses in Britain and Ireland. AB - REASONS FOR PERFORMING STUDY: There is limited information on the prevalence of idiopathic cheek teeth (CT) fractures in the general equine population and on which CT are most commonly affected. OBJECTIVES: To obtain information on the prevalence of fracture patterns and clinical details of idiopathic CT fractures. METHODS: Details of cases with idiopathic CT fractures encountered were obtained via a questionnaire sent to suitably experienced veterinary practitioners and equine dental technicians (EDTs). RESULTS: Details of 147 horses that suffered a total of 182 idiopathic CT fractures; and median 0.4% (range 0.07-5.9%) of horses examined were diagnosed with such fractures; 133 maxillary CT and 49 mandibular CT fractures were found; maxillary Triadan 09s and 10s were preferentially fractured (46% of all fractured CT); fracture patterns included maxillary CT slab fractures (through 1st and 2nd pulp chambers) in 87 teeth (48% of all fractured CT), maxillary CT midline sagittal fractures (through the infundibula) in 31 CT; and various other types of maxillary CT fractures in 15 CT. In the mandibular CT, lateral slab fractures (through the 4th and 5th pulp chambers) were found in 28 CT and a variety of other fracture patterns in the other 21 mandibular CT. Clinical signs included quidding in 33% of cases, bitting and behavioural problems (29%) and halitosis (12%), however 39% of horses with idiopathic CT fractures were asymptomatic. Treatments included oral extraction of the smaller dental fragment in 37% of cases, extraction of the entire fractured tooth (9%); removal of sharp edges on the remaining part of fractured tooth (14%); reduction of height of the opposite tooth (4%); other surgical or endodontic treatments, or referral of case for further investigation and treatment (10%); or no specific treatment (39%). Following treatment, 81% of cases were reported to be asymptomatic, 6% had ongoing clinical problems and the outcome was unclear in 13% of cases. CONCLUSIONS: Idiopathic CT fractures are present in approximately 0.4% of horses and may variably cause none to severe clinical signs. Most idiopathic CT fractures respond well to treatment. POTENTIAL RELEVANCE: Understanding of the prevalence, clinical findings and treatment of idiopathic CT fractures will improve management of these disorders. PMID- 17722724 TI - Equine idiopathic cheek teeth fractures: part 3: a hospital-based survey of 68 referred horses (1999-2005). AB - REASONS FOR PERFORMING STUDY: There is limited information available on the more serious sequellae of idiopathic cheek teeth (CT) fractures. OBJECTIVES: To obtain information on clinical and ancillary diagnostic findings in referred horses with idiopathic CT fractures. METHODS: Details of all horses suffering from idiopathic CT fractures referred to the Equine Hospital at the University of Edinburgh 1999 2005 were examined, and information concerning fracture patterns, clinical and ancillary diagnostic findings, treatments and long-term response to treatments were obtained and analysed. RESULTS: A total of 60 maxillary and 17 mandibular idiopathic CT fractures were diagnosed in 68 horses. Fracture patterns included maxillary CT lateral slab fractures (45%), maxillary CT midline sagittal fractures (16%) and various other patterns of maxillary CT fractures (17%). In the mandibular CT, lateral slab fractures were found (12%) and various other CT fracture patterns were present in 10%. The more centrally positioned CT (maxillary and mandibular Triadan 08s and 09) were preferentially fractured. Clinical signs included quidding in 47% of cases; bitting and behavioural problems (28%); signs of apical infection, including bony swellings and nasal discharge (21%); anorexia/weight loss (15%); halitosis (13%); and buccal food impaction (12%). The treatment of all cases was conservative whenever possible and included corrective rasping of the remaining tooth (46% of cases); oral extraction of the smaller and loose dental fragment (32%) and extraction of the entire fractured tooth by oral extraction (28%) or by repulsion (13%). Prophylactic treatment of adjacent, nonfractured CT with carious infundibula was possibly of value in preventing further midline sagittal maxillary CT fractures. CONCLUSIONS: Horses referred with idiopathic CT fractures frequently have clinical signs of apical infection of the fractured CT and these teeth require extraction, orally if possible. More conservative treatment of idiopathic CT fractures without signs of gross apical infection can resolve clinical signs in most cases. POTENTIAL RELEVANCE: In the absence of apical infection, extraction of only the loose dental fragments of CT with idiopathic fractures is usually successful. PMID- 17722726 TI - Magnetic resonance imaging evaluation of 264 horses with foot pain: the podotrochlear apparatus, deep digital flexor tendon and collateral ligaments of the distal interphalangeal joint. AB - REASONS FOR PERFORMING STUDY: To improve understanding of the interrelationships between injuries of the podotrochlear apparatus and deep digital flexor tendon (DDFT). HYPOTHESES: There is a difference in frequency of different types of lesions at different anatomical sites of the DDFT. Lesions of the collateral sesamoidean ligament (CSL), distal sesamoidean impar ligament (DSIL), distal interphalangeal (DIP) joint and navicular bursa are seen in association with lesions of the navicular bone. METHODS: The magnetic resonance (MR) images of 264 horses with unilateral or bilateral foot pain were analysed and graded. Descriptive statistics were performed to establish the frequency of occurrence of DDFT lesion types at different anatomical levels, and lesions of the CSL, DSIL, navicular bursa, DIP joint and collateral ligaments (CLs) of the DIP joint. A Chi square test was used to test for a difference in the proportion of navicular bone grades between limbs with and without DDFT lesions at each level, and to compare navicular bone grades for limbs with and without each of DSIL, CSL, navicular bursa or DIP joint lesions. RESULTS: Lesions of the DDFT occurred in 82.6% of limbs, occurring most commonly at the level of the CSL (59.4%) and the navicular bone (59.0%). Core lesions predominated at the level of the proximal phalanx (90.3%), whereas at the level of the CSL and navicular bone core lesions, sagittal splits and dorsal abrasions were most common. There was a positive association between DDFT lesions and navicular bone pathology involving all aspects of the bone. Lesions of the DSIL (38.2% limbs) were more common than those of the CSL (10.5%), but the presence of either was associated with abnormalities of the navicular bone, especially involving the proximal or distal borders and the medulla. CONCLUSIONS AND CLINICAL RELEVANCE: There are close interactions between injuries of the components of the podotrochlear apparatus, the DDFT, the navicular bursa and the DIP joint. Further knowledge about the biomechanical risk factors for injury may have importance for both disease prevention and management. PMID- 17722725 TI - Pulmonary response to airway instillation of autologous blood in horses. AB - REASONS FOR PERFORMING STUDY: Exercise-induced pulmonary haemorrhage (EIPH) occurs in the majority of horses performing strenuous exercise. Associated pulmonary lesions include alveolar and airway wall fibrosis, which may enhance the severity of EIPH. Further work is required to understand the pulmonary response to blood in the equine airways. OBJECTIVES: To confirm that a single instillation of autologous blood into horse airways is associated with alveolar wall fibrosis, and to determine if blood in the airways is also associated with peribronchiolar fibrosis. METHODS: Paired regions of each lung were inoculated with blood or saline at 14 and 7 days, and 48, 24 and 6 h before euthanasia. Resulting lesions were described histologically and alveolar and airway wall collagen was quantified. RESULTS: The main lesion observed on histology was hypertrophy and hyperplasia of type II pneumocytes at 7 days after blood instillation. This lesion was no longer present at 14 days. There were no significant effects of lung region, treatment (saline or autologous blood instillation), nor significant treatment-time interactions in the amount of collagen in the interstitium or in the peribronchial regions. CONCLUSION: A single instillation of autologous blood in lung regions is not associated with pulmonary fibrosis. POTENTIAL RELEVANCE: Pulmonary fibrosis and lung remodelling, characteristic of EIPH, are important because these lesions may enhance the severity of bleeding during exercise. A single instillation of autologous blood in the airspaces of the lung is not associated with pulmonary fibrosis. Therefore the pulmonary fibrosis described in EIPH must have other causes, such as repetitive bleeds, or the presence of blood in the pulmonary interstitium in addition to the airspaces. Prevention of pulmonary fibrosis through therapeutic intervention requires a better understanding of these mechanisms. PMID- 17722727 TI - Effects of an adapted intravenous amiodarone treatment protocol in horses with atrial fibrillation. AB - REASON FOR PERFORMING STUDY: Good results have been obtained with a human amiodarone (AD) i.v. protocol in horses with chronic atrial fibrillation (AF) and a pharmacokinetic study is required for a specific i.v. amiodarone treatment protocol for horses. OBJECTIVES: To study the efficacy of this pharmacokinetic based i.v. AD protocol in horses with chronic AF. METHODS: Six horses with chronic AF were treated with an adapted AD infusion protocol. The protocol consisted of 2 phases with a loading dose followed by a maintenance infusion. In the first phase, horses received an infusion of 6.52 mg AD/kg bwt/h for 1 h followed by 1.1 mg/kg bwt/h for 47 h. In the second phase, horses received a second loading dose of 3.74 mg AD/kg bwt/h for 1 h followed by 1.31 mg/kg bwt/h for 47 h. Clinical signs were monitored, a surface ECG and an intra-atrial electrogram were recorded. AD treatment was discontinued when conversion or any side effects were observed. RESULTS: Three of the 6 horses cardioverted successfully without side effects. The other 3 horses did not convert and showed adverse effects, including diarrhoea. In the latter, there were no important circulatory problems, but the diarrhoea continued for 10-14 days. The third horse had to be subjected to euthanasia because a concomitant Salmonella infection worsened the clinical signs. CONCLUSION: The applied treatment protocol based upon pharmacokinetic data achieved clinically relevant concentrations of AD and desethylamiodarone. POTENTIAL RELEVANCE: Intravenous AD has the potential to be an alternative pharmacological treatment for AF in horses, although AD may lead to adverse drug effects, particularly with cumulative dosing. PMID- 17722728 TI - Verification of scintigraphic imaging for injury diagnosis in 264 horses with foot pain. AB - REASONS FOR PERFORMING STUDY: Nuclear scintigraphy is commonly used as a diagnostic aid for foot pain, but there is limited information about different patterns of radiopharmaceutical uptake (RU) and their correlation with the results of other imaging modalities. OBJECTIVES: To describe patterns of RU in horses with foot pain. MATERIALS AND METHODS: Scintigraphic images of the feet of 264 horses with front foot pain were analysed subjectively and using region of interest analysis. Magnetic resonance images of all feet were analysed prospectively; the navicular bones were reassessed retrospectively and assigned a grade. A Spearman rank correlation test was used to test for a relationship between the scintigraphic grade of the navicular bone and magnetic resonance imaging (MRI) grade. Sensitivity and specificity of scintigraphy for detection of lesions in the deep digital flexor tendon (DDFT), the collateral ligaments (CL) of the distal interphalangeal (DIP) joint and the navicular bone were determined. RESULTS: Increased radiopharmaceutical uptake (IRU) was detected in: a) the navicular bone (36.6%); b) pool phase images in the DDFT (13.0%); and c) at the insertion of the DDFT on the distal phalanx (14.3%). There was focal IRU at the insertion of the medial or lateral CL of the DIP joint in 9.4% and 1.5% of limbs, respectively. There was IRU in the medial and lateral palmar processes in 7.6% and 3.4% of limbs, respectively. There was a significant positive correlation between the scintigraphy grade and total MRI grade for the navicular bone and no difference between either focal or diffuse IRU and total MRI grade. There was high specificity, but low sensitivity of scintigraphy for detection of MR lesions of the navicular bone, the DDFT and the CLs of the DIP joint. CONCLUSIONS: Positive nuclear scintigraphic results are good predictors of injury or disease of the navicular bone, DDFT and CLs of the DIP joint. However, a negative scintigraphic result does not preclude significant injuries. CLINICAL RELEVANCE: Nuclear scintigraphy is a useful tool in the investigation of foot lameness and may help to determine the significance of MR lesions, especially if >1 lesion is identified that may be contributing to lameness. PMID- 17722729 TI - Comparison of 2 methods of centesis of the bursa of the biceps brachii tendon of horses. AB - REASONS FOR PERFORMING STUDY: Centesis of the bicipital bursa using an 8.9 cm long spinal needle has been reported but the alternative of employing a 3.8 cm long hypodermic needle requires validation. OBJECTIVE: To compare the efficacy of 2 different methods of centesis of the bicipital bursa and to evaluate the usefulness of ultrasonographic imaging to determine the location of solution administered when centesis of the bursa is attempted. METHODS: For Trial 1, 6 clinicians, who had no previous experience of centesis of the bicipital bursa, attempted to inject a solution composed of an aqueous radiopaque contrast medium and physiological saline solution (PSS) into the bicipital bursae of 2/12 horses using the previously described distal approach to inject one bursa and a proximal approach to inject the contralateral bursa. The bicipital tendon and bursa were examined ultrasonographically before and after injection; and both shoulders were examined radiographically to identify the location of the medium. In Trial 2, another 6 clinicians, also with no previous experience of centesis, repeated Trial 1, using 6 horses, but the radiopaque contrast medium was mixed with air instead of PSS. RESULTS: Accuracy of centesis using the proximal approach was 39% and that of the distal approach 28%. Ultrasonographic examination of the shoulder allowed the location of solution and air to be accurately predicted in all 12 shoulders examined. CONCLUSIONS: Clinicians who have had no previous experience performing centesis of the bicipital bursa are unlikely to be successful in centesis using either approach. Radiographic examination after injecting a radiopaque contrast medium may be necessary to assess the success of centesis especially if bursal fluid is not obtained during centesis. Injecting air along with the radiopaque contrast medium provides more accurate ultrasonographic confirmation of centesis and better radiographic definition than does injection without air. PMID- 17722731 TI - Use of concurrent scintigraphic and magnetic resonance imaging evaluation to improve understanding of the pathogenesis of injury of the podotrochlear apparatus. AB - REASONS FOR PERFORMING STUDY: Use of physiological methods of diagnostic imaging could provide insight into the pathogenesis of foot pain in live horses. OBJECTIVES: To describe patterns and intensity of increased radiopharmaceutical uptake (IRU) in the navicular bone, and relate this to distribution and types of signal intensity change in the navicular bone and to the presence or absence of lesions of the related soft tissue structures detected using MRI. MATERIALS AND METHODS: Scintigraphic and MR images of 264 horses with unilateral or bilateral foot pain were analysed and graded. A Spearman rank correlation was used to test for relationships between scintigraphic grade of the navicular bone and MRI scores for each region of the bone. Chi-square tests were used to test for associations between scintigraphy grade and presence of increased signal intensities, for differences in the proportion of focal and diffuse IRU between MRI grades, and for associations between an abnormal scintigraphic grade of the navicular bone and presence or absence of a lesion. RESULTS: There were significant positive correlations between scintigraphy grade and both maximum and total MRI grades for the navicular bone and between scintigraphy grade and the MRI grades for the flexor border, the distal border and medulla. However, there was no difference in the proportions of focal and diffuse IRU between navicular bone MRI grades, although diffuse IRU was relatively under-represented in Grade 3 navicular bones. There was no association between IRU in the navicular bone and MR lesions of either the DSIL origin or the CSL insertion, however there was an association between IRU in the navicular bone and combined lesions of the CSL, DSIL and navicular bursa. In limbs with a DDFT lesion, navicular bone scintigraphic Grades 2 and 3 were over-represented. CONCLUSIONS AND CLINICAL RELEVANCE: Scintigraphy and MRI provide complementary information about the pathogenesis of lesions of the podotrochlear apparatus. Further understanding of these disease processes may eventually permit more targeted treatments. PMID- 17722730 TI - Equine laminitis: ultrastructural lesions detected 24-30 hours after induction with oligofructose. AB - REASONS FOR PERFORMING STUDY: The pathology of equine laminitis has been well documented 48 h after dosing with oligofructose when clinical lameness and lamellar disintegration is well advanced. Further analysis of the earliest lesions, by collecting lamellar samples at the first sign of foot lameness after oligofructose dosing is required in order to increase understanding of the disease. OBJECTIVES: To investigate lamellar epidermal hemidesmosome damage and basement membrane dysadhesion by transmission electron microscopy (TEM). METHODS: Eight clinically normal, mature Standardbred horses were divided randomly into 2 groups of 4. The treatment group were dosed with oligofructose (10 g/kg bwt) and subjected to euthanasia when shifting weight from one foot to other commenced and at the first sign of lameness during walking and turning. This occurred at 24 h in 3 horses and 30 h in one. The sham treatment control group were dosed with water and subjected to euthanasia after 48 h. Lamellar tissues of the front feet were harvested and processed for ultrastructural study using TEM. RESULTS: Examination by TEM showed excessive waviness of the basement membrane zone and pointed tips of some secondary epidermal lamellae, an ultrastructural lesion typical of laminitis. The average number of hemidesmosomes/microm of basement membrane was decreased and their distance from the centre of the lamina densa of the basement membrane was increased. CONCLUSIONS: Laminitis lesions are detectable 24 h after oligofructose administration. POTENTIAL RELEVANCE: Hindgut events occurring in the first 24 h after dosing have begun the destruction of the hoof lamellar interface. Prevention and treatment strategies should precede lameness if they are to be efficacious. PMID- 17722732 TI - Acute in vivo interactions of Helicobacter equorum with its equine host. AB - REASONS FOR PERFORMING STUDY: A novel urease-negative Helicobacter species has been isolated from faecal samples of clinically healthy horses, but no information is available about the main sites of colonisation in the equine gastrointestinal tract nor is the pathogenic potential of this microorganism known. An experimental infection in horses was therefore carried out. METHODS: Four horses were infected with H. equorum strain CCUG 52199T and subjected to euthanasia at 10 (n = 2) and 30 days (n = 2) post inoculation. A fifth animal was inoculated with phosphate buffered saline and used as control. Gastrointestinal samples were examined histologically and bacteriologically. These samples, as well as faecal material collected at regular intervals, were also subjected to PCR analysis. RESULTS: All horses remained clinically healthy and no specific macroscopic lesions were identified, nor were there any microscopic changes. H. equorum-DNA was detected in the faeces during the whole experiment in all infected animals but not in the negative control. Sites of colonisation were caecum, colon and rectum. CONCLUSIONS: H. equorum is able to colonise the equine lower bowel and is excreted in faeces without apparent pathology. No association between the presence of the organism and gastrointestinal disease was demonstrated. PMID- 17722733 TI - Physiology of equine performance and associated tests of function. AB - This review addresses the physiology of performance horses in the context of functional tests aimed at assisting clinicians in the search for explanations of the individual's limitations, actual or perceived as below expectation. The intention is to assist clinicians who are faced frequently by owners or trainers seeking explanations for poor performance; and for research workers as a basis on which to proceed in their search for new methodologies, particularly those that can be applied in the field as for treadmill exercise. The review sets out fundamental physiological pathways, the entailment of which may represent a limiting factor to performance, while taking into account the individual's status, including anamnesis and the possibility of actual disease being present. Tests that assess the possible roles of several body systems, as causes of limited performance, are discussed. These systems include pulmonary, cardiovascular and neuromuscular systems. The evaluation of anaerobic and aerobic energy pathways is also discussed. Emphasis is given to the assessment of pulmonary ventilation by techniques such as spirometry and ergospirometry. These techniques are considered to be of particular potential for further development. PMID- 17722734 TI - Harmful effects and acute lethal toxicity of intravenous administration of low concentrations of hydrofluoric acid in rats. AB - The acute toxicity of hydrofluoric acid (HFA) was investigated in a 24-h lethal dose study of intravenous infusion in rats. The lethal dose lowest (LDLo) and LD50 were 13.1 and 17.4 mg/kg, respectively. Harmful systemic effects were also studied 1 h after acute sublethal exposure to HFA. The maximum dose was set at 9.6 mg/kg (LD5). Rats were injected with HFA (1.6, 3.2, 6.4 or 9.6 mg/kg), saline, sodium fluoride (NaF) or HCl solution. NaF and HCl solution concentrations corresponded to the F- and H+ concentrations of 9.6 mg/kg HFA. Blood urea nitrogen (BUN) and Cr were significantly increased in response to HFA concentrations greater than 3.2mg/kg. Acute glomerular dysfunction also occurred at HFA concentrations greater than 3.2 mg/kg. HCO3- and base excess (BE) were significantly decreased in the 6.4 and 9.6 mg/kg groups. Ca2+ was significantly decreased, and K+ was increased in the 9.6 mg/kg group. BUN was significantly increased in the NaF and HFA groups and was increased in the HFA group compared with that in the NaF group. Cr was significantly increased in the HFA group only. HCO3- and BE were significantly decreased in the NaF and HFA groups and were increased in the HFA group compared with values in the NaF group. Ca2+ was significantly decreased in the NaF and HFA groups, and K+ was significantly increased in the NaF and HFA groups. F- exposure directly affected serum electrolytes. Mortality was thought to be due to cardiac arrhythmia resulting from hypocalcemia and hyperkalemia. Metabolic acidosis and renal failure were more severe in response to HFA exposure than in response to NaF exposure because of more free F-, which has strong cytotoxicity, in the HFA group than in the NaF group. Lethal effects of HFA are promoted by exposure routes such as inhalation that cause rapid absorption into the body. Even low exposure to HFA can cause acute renal dysfunction, electrolyte abnormalities and metabolic acidosis. These complications result in a poor prognosis. PMID- 17722735 TI - The effects of diazinon on lipid peroxidation and antioxidant enzymes in rat erythrocytes: role of vitamins E and C. AB - Reactive oxygen species caused by organophosphates may be involved in the toxicity of various pesticides. Therefore, in this study, we aimed to investigate the effects of acute exposure to organophosphate insecticide diazinon (DI) and possible ameliorating role of vitamins E and C, with the following parameters: lipid peroxidation (LPO) and the activity of the glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in rat erythrocytes. The experimental groups were arranged as control group, DI-treated group (DI) and DI + vitamin E + vitamin C treated group (DI + Vit). DI + Vit groups were treated orally with a single dose of 335 mg/kg DI body weight. Vitamins E and C were injected at doses of 150 mg/kg body weight intramuscular (in) and 200 mg/kg body weight intraperitoneal (ip), respectively, 30 min after the treatment of DI in DI + Vit group. Blood samples were taken 24 h after the DI. The results showed that DI administration caused to increase in LPO and the activities of SOD and GSH-Px enzymes in erythrocytes. Also, the combination of vitamins E and C decreased LPO and the activities of GSH Px and SOD compared with the DI group. In conclusion, although treating rats with single dose DI increases LPO and antioxidant enzyme activities in erythrocytes, vitamins C and E combination can reduce LPO caused by DI. PMID- 17722736 TI - An in vitro blood culture for evaluating the genotoxicity of titanium dioxide: the responses of antioxidant enzymes. AB - Titanium dioxide (TiO2) is extensively used in many industrial areas, including cosmetics, pharmaceutical, paint and paper production. Although the uses of TiO2 have become so widespread, there is limited information concerning its toxicity on humans. However, the genotoxicity of TiO2 remains to be controversial. The possible genotoxic effects of TiO2 have been evaluated in human whole blood cultures (WBCs) related to oxidative status. The blood was processed to examine the following oxidative stress markers: glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase. In addition, the frequencies of sister-chromatid exchanges (SCEs) and micronuclei (MN) were scored as genetic endpoints. Different concentrations of TiO2 (1, 2, 3, 5, 7.5 and 10 microM) were tested. From the results, it appeared that TiO2 was able to induce genotoxic effects, as observed by the increases found in SCE and MN frequencies in TiO2 treated cultures. Present results also show that treatments with TiO2 promoted oxidative stress in human WBC with an increase in concentrations. In conclusion, our data indicate that TiO2 can enhance oxidative stress-mediated DNA damage in vitro. PMID- 17722737 TI - Altered cholinergic metabolism and muscarinic receptor linked second messenger pathways after chronic exposure to dichlorvos in rat brain. AB - Chronic dichlorvos exposure (6 mg/kg b.wt/day) for a period of 8 weeks resulted in significant reduction in body weight gain of the male Wistar rats. However, the dietary intake remained unchanged in experimental animals following dichlorvos treatment. Activity of the synthesizing enzyme of acetylcholine (ACh) ie, choline acetyltransferase, was found to be significantly increased and the activity of hydrolyzing enzyme, acetyl cholinesterase (AChE), was inhibited in all the three brain regions studied. Chronic dichlorvos treatment also caused significant reduction in both high affinity (HA) and low affinity (LA) choline uptake (CU), with maximal effect being observed in the brain stem followed by cerebellum and cerebrum. Muscarinic receptor binding was significantly decreased in brain stem and cerebellum as reflected in the decreased receptor number (B(max)), without any change in the binding affinity (K(d)) of the receptors. Dichlorvos treatment caused marked inhibition in cAMP synthesis as indicated by decreased adenylate cyclase activity as well as cAMP levels in cerebrum, cerebellum and brain stem. Our study shows that organophosphates may interact with muscarinic receptor-linked second messenger system and this could be a potential mechanism for the neurotoxic effects observed after repeated exposure to low levels of organophosphates, which are unexplainable on the basis of cholinergic hyperactivity. PMID- 17722738 TI - Predicting human skin absorption of chemicals: development of a novel quantitative structure activity relationship. AB - The objective of this study was to construct and validate a quantitative structure-activity relationship model for skin absorption. Such models are valuable tools for screening and prioritization in safety and efficacy evaluation, and risk assessment of drugs and chemicals. A database of 340 chemicals with percutaneous absorption was assembled. Two models were derived from the training set consisting 306 chemicals (90/10 random split). In addition to the experimental K(ow) values, over 300 2D and 3D atomic and molecular descriptors were analyzed using MDL's QsarIS computer program. Subsequently, the models were validated using both internal (leave-one-out) and external validation (test set) procedures. Using the stepwise regression analysis, three molecular descriptors were determined to have significant statistical correlation with K(p) (R2 = 0.8225): logK(ow), X0 (quantification of both molecular size and the degree of skeletal branching), and SsssCH (count of aromatic carbon groups). In conclusion, two models to estimate skin absorption were developed. When compared to other skin absorption QSAR models in the literature, our model incorporated more chemicals and explored a large number of descriptors. Additionally, our models are reasonably predictive and have met both internal and external statistical validations. PMID- 17722739 TI - Toxicity of pharmaceutical wastewater on male reproductive system of Mus musculus. AB - This study reports on the toxic effects of 35-days intragastric perfusion of pharmaceutical wastewater on the male reproductive system of Mus musculus. Flow cytometric analyses and staining with fluorescein diacetate (FDA) and propidium iodide (PI) were used to assess the toxicity on spermatogenic cells. Significant depletions in the relative percentages of elongated spermatid (HC), diploid spermatogonia (2C), and S-phase cells were observed. These alterations in different germ cell populations were reflected in the various germ cell ratios. The ratios of 1C:4C and HC:2C showed a significant decline after pharmaceutical wastewater treatment, while the 4C:2C and 1C:2C ratios increased significantly. FDA and PI staining displayed reduced viability of spermatogenic cells in wastewater treated group. Statistically significant percentages of sperm abnormalities showed the genotoxic potential of this pharmaceutical wastewater. Testicular histopathological studies of treated animals revealed expansion of interstitial space and reduction in the number and size of Leydig cells. Thus, the present study has established the toxicity of pharmaceutical wastewater on the reproductive biology of male mice. PMID- 17722740 TI - Risk assessment of occupational exposure to polycyclic aromatic hydrocarbons by means of urinary1-hydroxypyrene. AB - Polycyclic aromatic hydrocarbons have mutagenic and carcinogenic properties and some of them are classified as probable or possible human carcinogens. Aim of this study was to evaluate the genotoxic risk in workers exposed to diesel exaust. Environmental and biological monitoring exposure to polycyclic aromatic hydrocarbons was carried out on fifty-two workers exposed to diesel exhaust. Urinary 1-hydroxypyrene was employed as a biomarker of internal dose. Significant urinary 1-hydroxypyrene differences between smokers and non-smokers were found. Twenty per cent of urinary 1-hydroxypyrene values exceeded benchmark level for genotoxic effect, while the results of environmental monitoring excluded the existence of exposure to polycyclic aromatic hydrocarbons. In the absence of greater knowledge about the relationship between urinary 1-hydroxypyrene and genotoxic effects under the conditions of very low exposure, extreme caution is recommended when this biomarker of internal dose is employed as an indicator of genotoxic risk. PMID- 17722741 TI - Novel therapeutic avenues in myeloma: changing the treatment paradigm. AB - Our better understanding of the complex interaction of multiple myeloma (MM) cells with their bone marrow microenvironment and the signaling pathways that are dysregulated in this process has resulted in a dramatic increase in the therapeutic agents available for this disease. A number of these new agents have demonstrated significant activity in patients with MM. Over the past 5 years, three drugs have received approval from the US Food and Drug Administration for therapy in MM--bortezomib, thalidomide, and lenalidomide. To date, the choice of therapy for MM is not individualized according to the biologic characteristics of the disease, but future studies should enable us to identify patients who may benefit most from certain therapeutic interventions, and thus develop individualized therapy for MM. In this review, we will present some of the treatment algorithms currently developed for patients with MM and focus on established advances in therapy, specifically with thalidomide, bortezomib, and lenalidomide. We will also discuss some of the emerging novel therapeutic agents showing promise in phase I/II clinical trials in MM. PMID- 17722742 TI - Pediatric cancers in the new millennium: dramatic progress, new challenges. AB - Over the past 50 years, great strides have been made in diagnosis, treatment, and survival of childhood cancer. In the 1960s the probability of survival for a child with cancer was less than 25%, whereas today it may exceed 80%. This dramatic change has occurred through significant and steady progress in our understanding of tumor biology, creation of specialized multidisciplinary care teams, incremental improvements in therapy, establishment of specialized centers with research infrastructure to conduct pivotal clinical studies, and the evolution of a cooperative group mechanism for clinical research. Most children with cancer in the United States, Europe, and Japan receive appropriate diagnosis and treatment, although access is limited in developing countries. The price of success, however, is the growing population of survivors who require medical and psychosocial follow-up and treatment for the late effects of therapy. Here we review the progress made in pediatric oncology over the past 3 decades and consider the new challenges that face us today. PMID- 17722743 TI - Association between the rates of synchronous and metachronous metastases: analysis of SEER data. AB - Patients with cancer are usually staged based on the presence of detectable regional and/or distant disease. However, staging is inexact and cM0 patients may have microscopic metastases (cM0pM1) that later cause relapse and death. Since the clinical tools used to stage patients are fairly similar for different tumors, the ratio of the rates of metachronous to synchronous metastases should be similar for different tumors (hypothesis #1). Improvements in diagnostic tools should have caused the ratio of metachronous-to-synchronous metastases to have decreased over time (hypothesis #2). Finally, the fraction of patients with either metachronous or synchronous metastases should have declined over time due to increased screening and earlier diagnoses (hypothesis #3). To test these hypotheses, Surveillance, Epidemiology, and End Results (SEER) data from 1973 1998 were analyzed for 19 solid tumors. A linear relationship was seen between the rates of metachronous and synchronous metastases, with modestly strong correlation coefficients, consistent with hypothesis #1. Over time, changes in staging methods have not significantly altered the ratio of metachronous/synchronous metastases, contrary to hypothesis #2. Also over time, a decrease in the number of patients with metastases was found, consistent with hypothesis #3. Therefore, the rate of anticipated metachronous metastases can be estimated from the rate of clinically evident metastases at presentation. Changes in screening/staging of disease over time may have reduced the overall fraction of patients with metastases. PMID- 17722744 TI - Cost considerations in the management of cancer in the older patient. AB - Patients aged 65 years and older represent 12% of the US population yet account for approximately 56% of cancer cases and 69% of all cancer mortalities. The overall cost of cancer in 2005 was $209.9 billion--$74 billion for direct medical costs and $118.4 billion for indirect mortality costs. This paper considers the direct, indirect, and out-of-pocket expenditures incurred by cancer patients > or = 50 years of age. Several major empirical studies on supportive care for older patients and cancer-related costs were reviewed. Insurance coverage, hematologic malignancies, squamous cell carcinoma of the head and neck, and cancers of the breast, prostate, colorectum, and lung were evaluated. Major sources of direct medical expenditures covered by third-party insurers for patients aged 65 years and older include extended length of hospital stay, home health assistance following hospital discharge, adjuvant prescription medications, lower-risk treatment (for prostate cancer), and advent of new pharmaceuticals (for colorectal cancer). The mean total direct medical cost for breast cancer is $35,164, and the cumulative cost for prostate cancer is $42,570. Emerging targeted cancer drug costs range from $20,000 to $50,000 annually per patient. Additional clinical trials and cost-effective treatments are needed for older patients to ameliorate the disproportionate economic burden among older individuals with cancer. Additional research about cancer costs may also lead to reforms in cancer care reimbursement, and therefore provide access to affordable health care for older patients. PMID- 17722745 TI - Intracystic papillary carcinoma of the breast: differential diagnosis and management. PMID- 17722746 TI - ASCO 2007: plenary top 5. PMID- 17722747 TI - Medicare's drug discount card program: beneficiaries' experience with choice. AB - This article describes Medicare beneficiaries' experience with the choice among Medicare drug discount cards and is based primarily on surveys and focus groups with beneficiaries as well as interviews with other stakeholders. Although competition and choice have the potential to reduce cost and enhance quality in the Medicare Program, our findings highlight some of the challenges involved in making choice work in practice. Despite the unique and temporary nature of the drug discount card program, these findings have considerable relevance to the Part D drug benefit and to other Medicare initiatives that rely on choice. PMID- 17722748 TI - Diagnosis-based risk adjustment for medicare prescription drug plan payments. AB - The 2003 Medicare Prescription Drug, Improvement, and Modernization Act (MMA) created Medicare Part D, a voluntary prescription drug benefit program. The benefit is a government subsidized prescription drug benefit within Medicare. This article focuses on the development of the prescription drug risk-adjustment model used to adjust payments to reflect the health status of plan enrollees. PMID- 17722749 TI - Medicaid's expenditures for newer pharmacotherapies for adults with disabilities. AB - Medicaid's drug expenditures have grown at double-digit inflation rates since 2000. These prescription drug costs are important contributors to increasing health care costs for disabled persons. In spite of this knowledge, little has been reported about specific patterns of medication use among disabled enrollees. We analyzed Kansas Medicaid data to describe trends in medication use patterns across 3 years among disabled beneficiaries. The marked shifts toward newer medications and disproportionate contributions of newer, more expensive medications to overall prescription costs for antipsychotics, antidepressants, anticonvulsants, antiulcer medications, anti-inflammatory agents, and opioids have implications for both policy and practice. PMID- 17722750 TI - Prescription drug use and expenditures among dually eligible beneficiaries. AB - Using Medicaid Analytic eXtract (MAX) claims files for 1999 and 2001, the authors describe patterns of prescription drug use and expenditures among dually eligible Medicare and Medicaid beneficiaries for all Medicaid full dually eligible beneficiaries and three important subgroups: (1) aged, (2) disabled, and (3) full year nursing home residents. The analyses indicate great variation in use and expenditures across States that cannot be explained through differences in use of cost containment strategies. Further, the findings suggest that Medicare Part D plans may achieve significant savings by providing incentives for greater use of generic drugs. PMID- 17722751 TI - Disabled Medicare beneficiaries by dual eligible status: California, 1996-2001. AB - This highlight describes the characteristics and inpatient utilization of under age 65 disabled California Medicare beneficiaries by dual eligible status (i.e., Medicaid State buy-in coverage or not). More disabled dually eligible beneficiaries are younger, non-White, and in fee-for-service (FFS) than non dually eligible beneficiaries. Disabled dually eligible beneficiaries experienced consistently higher hospitalization rates and average length of stay (LOS) than nondually eligible beneficiaries from 1996 to 2001. Inpatient days remain higher among dually eligible beneficiaries when stratified by the system of care, age, sex, or race. In addition, the hospitalization rate of disabled dually eligible beneficiaries was higher for most diagnoses, but how much higher varied by condition. PMID- 17722752 TI - Medicaid's role in the many markets for health care. AB - To illuminate Medicaid's growing role as a health care purchaser, we estimated Medicaid spending and market shares for 30 markets defined by provider category of service. For approximately 15 markets, our estimates are more detailed than the data available from standard sources. Two-thirds of Medicaid spending occurs in markets where the program has a modest market share. The other one-third occurs in markets that Medicaid dominates, especially in the areas of long-term care (LTC), mental retardation, and mental health. We explore the implications of the different roles for payment policy, industry organization, data availability, and quality of care. PMID- 17722753 TI - Physician code creep: evidence in Medicaid and State Employee Health Insurance billing. AB - This study estimates a fixed effects ordered logit model physician office visit billing using claims data from South Carolina Medicaid and the State Employees Health Plan. The results find code creep increasing expenditures on physician office visits at a rate of 2.2 percent annually for both programs, with no significant difference in the rate between the two. The models also indicate that physician billing patterns differ between the programs, with the Medicaid claims averaging 1.3 percent less per visit than comparable State Employees Health Plan claims. PMID- 17722754 TI - Evolution of state outreach efforts under SCHIP. AB - States have shown creativity and adaptability in developing outreach strategies to promote State Children's Health Insurance Program (SCHIP) enrollment. As the program has matured and the fiscal environment has tightened, States have learned what efforts are successful and have tailored their approaches accordingly. This article reviews the evolution of State outreach strategies under SCHIP, using qualitative information from all 50 States and the District of Columbia. Early campaigns were aimed at building broad awareness of SCHIP. Over time, States have adapted their outreach campaigns to close the gaps in enrolling hard-to-reach populations, by modifying their target populations, messages, methods, organizational strategies, and emphasis. PMID- 17722756 TI - Lighting the way to interdisciplinary primary health care. AB - Between 2004 and 2006, the Enhancing Interdisciplinary Collaboration in Primary Health Care (EICP) initiative undertook research on interdisciplinary collaboration. The last report prepared by the Initiative, Interdisciplinary Primary Health Care: Finding the Answers - A Case Study Report, offers a research based blueprint for action by showcasing some current successful collaborative practices in primary health care. Several key learnings are discussed, especially in areas such as health human resources, funding, liability, regulation, information and communication technologies, management and leadership and planning and evaluation. Each of the primary health care organizations that were studied has created very different organizational cultures and teams. Each has faced different obstacles and developed innovative solutions to overcome them, indicating that there is no single right way, no step-by-step prescription as how to best pursue this method of care. Their innovative approaches are enlightening the way to interdisciplinary primary health care. PMID- 17722755 TI - Partially capitated managed care versus FFS for special needs children. AB - Little research has examined whether Medicaid managed care plans (MCPs) that incorporate case management are effective in coordinating services for children with special health care needs (CSHCN). This study evaluates the effects of enrollment of special needs children into a partially capitated MCP (with ongoing case management) versus the fee-for-service (FFS) option on use of therapeutic services, specifically speech, occupational, and physical therapy by site of service (school versus health care sector). Results show that special needs children enrolled in the partially capitated MCP are significantly more likely to obtain occupational and physical therapy at school relative to their FFS counterparts. Moreover, children enrolled in FFS are significantly less likely to be either regular or frequent users of each type of therapy relative to children enrolled in managed care. We attribute much of these disparities in use of therapeutic services at school to the availability of case management and coordination that is an integral component of the partially capitated MCP. PMID- 17722757 TI - Models of primary care service delivery in Ontario: why such diversity? AB - A surprisingly large and ever-growing number of alternative models of primary care service delivery have been developed in Ontario. The models are relatively poorly understood, and it is unclear why there are so many of them. What needs of providers and of government as payer are they attempting to address? Through a literature review and interviews with key informants, we sought to explain why there are so many models. PMID- 17722758 TI - Primary mental health care reform: catch the wave. AB - There is growing energy behind primary mental health care reform - from political activity, research, funding and clinical practice. The evidence that early adopters have been busy reforming mental health services in primary health care is apparent in the rise of references to primary mental health care and collaborative care in national and provincial planning documents, clinical trials examining the efficacy of collaborative mental health care, funded clinical programs across the country, and the establishment of a nationally funded initiative - the Canadian Collaborative Mental Health Initiative - to research and develop tools to implement collaborative mental health care. In conclusion, there is real momentum in primary mental health care reform. Health care planners and executives will want to turn their attention to collaborative care as the benefits to individuals and their families, the health care system, and to the economy are clear. PMID- 17722759 TI - A comprehensive approach to effectively engage physicians during a hospital closure: using the physician engagement model. AB - In 2003, St. Vincent's Hospital (SVH) closed its doors. The authors investigate the involvement of the medical staff in the successful closure of SVH using the Physician Engagement (PE) Model. This 10-strategy model is based on engagement, communication, education and support. Results were gathered by surveys, unstructured interviews and meetings. Data suggested that engaging physicians in the process was favourable, particularly by using the PE model. Six recommendations are given to assist administrators/decision-makers in future closures. PMID- 17722760 TI - CCHSE president Bonnie Adamson envisions college as "a gold standard learning organization". Interview by Dan Levitt. PMID- 17722761 TI - ESPR Subject Area 4 'Environmental Education, Science Communication, Science & Policy, Health Issues'. PMID- 17722762 TI - The fate of dissolved organic carbon (DOC) in the wastewater treatment process and its importance in the removal of wastewater contaminants. AB - GOAL, SCOPE AND BACKGROUND: Dissolved organic carbon (DOC) constitutes a parameter of organic pollution for waters and wastewaters, which is not so often studied, and it is not yet regulated by directives. The term 'DOC' is used for the fraction of organics that pass through a 0.45 microm pores' size membrane. The type of wastewater plays an important role in the quality of DOC and it has been shown that DOC may contain aquatic humic substances, hydrophobic bases, hydrophobic neutrals, hydrophilic acids, hydrophilic bases and hydrophilic neutrals. The quality of the DOC is expected to affect its fate in a wastewater treatment plant (WWTP), since a considerable fraction of DOC is not biodegradable, and it may be released in the aquatic environment together with the treated effluent. In the present study, the occurrence of DOC during the wastewater treatment process is investigated and its removal rates during primary, secondary and overall treatment are being estimated. Furthermore, a correlation is being attempted between DOC and the concentrations of selected Persistent Organic Pollutants (POPs) and Heavy Metals (HMs) in the dissolved phase of wastewaters, to examine whether there are common sources for these pollution parameters in WWTPs. Also, DOC is being correlated with the partition coefficients of the above-mentioned pollutants in wastewater, in order to examine the effect of 'solubility enhancement' in WWTPs and to evaluate the result of this phenomenon in the efficiency of a WWTP to remove organic pollutants. METHODS: For the purposes of this study, 24-h composite wastewater samples were collected from the influent (raw wastewater, RW), the effluent of primary sedimentation tank (primary sedimentation effluent, PSE) and the effluent of secondary sedimentation tank (secondary sedimentation effluent, SSE). Samples were analyzed for the presence of 26 POPs (7 PCBs and 19 organochlorine pesticides), 8 HMs and DOC. RESULTS AND DISCUSSION: Mean concentrations of DOC in RW and PSE were at similar levels (approximately 70 mg l(-1)), suggesting that primary treatment has a minor effect on the DOC content of wastewater. DOC concentrations in SSE were significantly lower (approximately 19 mg l(-1)) as a result of the degradation of organic compounds in the biological reactor. Calculated removals of DOC were 0.8% in the primary treatment, 63% in the secondary treatment, and 69% in the overall treatment, exhibiting large differences from other organic pollution parameters, such as BOD and COD. The overall DOC removal was found to be independent from the DOC concentration in raw wastewater. Poor correlation was also observed between the DOC content and the concentrations of wastewater contaminants, such as persistent organic pollutants (POPs) and heavy metals (HMs), probably suggesting that their occurrence in WWTPs is due to different sources. A good negative linear relationship was revealed between DOC concentrations and the logarithms of the distribution coefficients (Kd) of various POPs and HMs between the solid and the liquid phases of wastewater. This relationship suggests that DOC facilitates hydrophobic pollutants to remain in the dissolved phase thus causing lower removal percentages during the treatment process. CONCLUSION: DOC was measured at three stages of a municipal WWTP that receives mainly domestic wastewater and urban runoff. DOC concentrations in untreated and primarily treated wastewater were almost equal, and only after the secondary sedimentation there was a decrease. Concentrations and removal rates of DOC were in the same levels as in other WWTPs that receive municipal wastewater. The origin of DOC was found to be different to the one of POPs and of HMs, as no correlation was observed between the concentrations of DOC and the concentrations of these pollutants. On the contrary, DOC was found to have significant negative correlation with the Kd of all pollutants examined, suggesting that it plays an important role in the partitioning of those pollutants between the dissolved and the sorbed phase of wastewaters. This effect of DOC on partitioning can affect the ability of WWTPs to remove toxic pollutants, and that way it facilitates the discharge of those chemicals in the aquatic ecosystems together with the treated effluent. RRECOMMENDATION:By the results of this work it is shown that the presence of DOC in wastewaters can significantly affect the partition of hazardous pollutants between the dissolved and the sorbed phase. It is therefore of importance that this parameter is controlled more in wastewaters, since it can cause a decrease in the efficiency of WWTPs to remove quantitatively persistent pollutants. PMID- 17722763 TI - Knowledge transfer initiative between molecular biologists and environmental researchers and regulators. AB - A Natural Environment Research Council (NERC) funded Knowledge Transfer (KT) workshop was held in the United Kingdom (UK) to identify the needs and opportunities in the application of molecular biology and 'omics' techniques to environmental monitoring and risk assessment. Attendees highlighted a lack of effective communication between end-users and researchers as well as difficulties with data interpretation as reasons behind the slow uptake of molecular biology and omics techniques. A number of promising areas in which new techniques could be implemented at a practical level in the very near future were identified, thereby raising the profile of these recent technologies and providing vital proof of concept work. Molecular taxonomy, bacterial source tracking and pre screening of chemicals for potential toxicities were all viewed as areas in which omics and molecular techniques could have immediate value, with the aim of reducing cost, increasing efficiency and providing more comprehensive data of improved quality. PMID- 17722764 TI - Water protection against pollution. Conceptual framework for a science-policy interface. AB - Science-policy integration is one of the many complex challenges that scientific and policy-making communities are facing. It involves knowledge sharing and exchanges among a wide range of disciplines and actors. In many instances, the lack of proper communication and of a coordination mechanism leads to research outputs not being used or simply known by policy-makers, and to policy research needs not being communicated to the scientific communities in a timely fashion. This paper discusses the integration of scientific and technological progress into the policy-making and implementation process, with emphasis on water policies. It highlights the need and complexity of developing a knowledge-based approach which would enable to lead to an operational science-policy interface linked to WISE (Water Information System for Europe), including the newly developed WISE-RTD webportal (http://www.wise-rtd.info/). PMID- 17722765 TI - Derivation of soil values for the path 'soil-soil organisms' for metals and selected organic compounds using species sensitivity distributions. AB - BACKGROUND, AIMS AND SCOPE: According to the German Federal Soil Protection Act, the natural function of soil as a habitat for human beings, animals, plants and soil organisms is, among other things, to be protected by deriving soil values for important chemicals regarding their amounts in the environment, their persistence and/or their toxicity. This contribution presents the results of the mathematical derivation of such values for nine metals and ten organic substances from soil ecotoxicological effect values available in the literature for microbial processes, plants and soil invertebrates. MATERIAL AND METHODS: Ecotoxicological data were mostly extracted from published papers and reports and had to originate from valid studies that were performed according to internationally standardised guidelines (e.g. ISO) or were otherwise well documented, plausible and performed according to accepted laboratory practice. As test results, both structural (i.e., effects on mortality, growth or reproduction) and functional (i.e., effects on microbial activity or organic matter breakdown) parameters were included. The derivation of soil values was performed using the distribution based extrapolation model (DIBAEX) and EC(50)s (Effective Concentration) as input data. RESULTS: For 19 compounds, soil values could be calculated. In 18 of these 19 cases clear laboratory ecotoxicological effects (i.e., EC50 values) below the calculated soil value have been found in the literature. DISCUSSION: In those few cases where a comparison with field studies is possible, effects have been observed in the same order of magnitude as the calculated soil values. A comparison with other similar approaches confirmed the plausibility of the calculated values. CONCLUSIONS: The DIBAEX-method is a feasible and widely accepted method for deriving soil values from ecotoxicological input data. Data availability was already satisfactory for some substances, but other substances, especially organics, were only poorly covered. The soil values presented here were based on EC50 input data. However, depending on the protection level aimed at by using soil values in legislation, it might be appropriate to use other input data such as NOECs in the derivation process. RECOMMENDATIONS AND PERSPECTIVES: It is recommended to generate an appropriate number of data for further relevant substances by means of a test battery or multi-species approaches such as terrestrial model ecosystems. These tests should also consider the influence of the bioavailability of substances. A final recommendation for legally binding soil values demands a plausibility check of the mathematically derived values. This should include a comparison with natural background concentrations, soil values for other pathways and soil values used in legislation of other countries. Finally, expert judgement always has to be considered. PMID- 17722766 TI - Decolourization and removal of some organic compounds from olive mill wastewater by advanced oxidation processes and lime treatment. AB - BACKGROUND: Olive mill wastewater (OMW) generated by the olive oil extracting industry is a major pollutant, because of its high organic load and phytotoxic and antibacterial phenolic compounds which resist biological degradation. Mediterranean countries are mostly affected by this serious environmental problem since they are responsible for 95% of the worldwide olive-oil production. There are many methods used for OMW treatment, such as adsorption, electro coagulation, electro-oxidation, biological degradation, advanced oxidation processes (AOPs), chemical coagulation, flocculation, filtration, lagoons of evaporation and burning systems, etc. Currently, there is no such economical and easy solution. The aim of this study was to evaluate the feasibility of decolourization and removal of phenol, lignin, TOC and TIC in OMW by UV/H2O2 (AOPs). The operating parameters, such as hydrogen peroxide dosage, times, pH, effect of UV and natural sunlight were determined to find the suitable operating conditions for the best removal. Moreover, there is no study reported in the literature related to the use of METHODS: OMW was obtained from an olive-oil producing plant (Mugla area of Turkey) which uses a modern production process. No chemical additives are used during olive oil production. This study was realised by using two different UV sources, while taking the time and energy consumption into consideration. These two sources were mercury lamps and natural sunlight. Before starting AOPs experiments, one litre of OMW was treated by adding lime until a pH of 7.00. Then, 100 ml was taken from each sample, and 1 to 10 ml of a 30% H2O2 (Riedel deHaen) solution was added. These solutions in closed vessels were laid in the natural sunlight for a week and their compositions and colour changes were analysed daily by UV-Vis spectrophotometer. At the end of the one-week period, they were treated with lime. In this study, the effect of changes in the initial pH, times and H2O2 concentrations on removal was investigated. At the end of all experiments, changes in colour, phenol, lignin, TOC and TIC concentrations were analysed according to standard methods. RESULTS AND DISCUSSION: In the samples exposed to natural sunlight and having an H2/OMW ratio of 3 ml/100 ml, a significant colour removal was achieved approximately 90% of the time at the end of 7 days. When the same samples were treated with lime (pH: up to 7), 99% efficiency was achieved. When phenol and lignin removals were examined in the same concentration, phenol and lignin removal were found 99.5%, 35%, respectively. However, for maximum lignin removal, more use of H2O2 (10 ml H2O2/100 ml OMW) was found to be necessary. Under these conditions, it was found that lignin can be removed by 70%, but to 90% with lime, at the end of a seven day period. Rate constants obtained in the experiments performed with direct UV were found to be much higher than those of the samples exposed to natural sunlight (k(a)lignin=0.3883>> k(b)lignin=0.0078; k(a)phenol=0.5187>> k(b)phenol = 0.0146). Moreover, it should be remembered in this process that energy consumption may induce extra financial burden for organisations. CONCLUSIONS: It was found, in general, that colour, lignin, total organic carbon and phenol were removed more efficiently from OMW by using H2O2 UV and lime OMW. Moreover, in the study, lime was found to contribute, both initially and after radical reactions, to the efficiency to a great extent. RECOMMENDATIONS AND PERSPECTIVES: Another result obtained from the study is that pre-purification carried out with hydrogen peroxide and lime may constitute an important step for further purification processes such as adsorption, membrane processes, etc. PMID- 17722767 TI - Determination of PCDDs, PCDFs, PCBs and HCB emissions from the metallurgical sector in Poland. AB - BACKGROUND: The aim of the project was to measure the actual emissions of PCDD/F, PCBs and HCB from 20 selected metallurgical installations in Poland, in order to update the national inventory of dioxin emission from metallurgical industry for developing a strategy for dioxins and furans emission abatement from the subject facilities (UNEP 2005). METHODS: Sampling methodology used in this work was developed at the Cracow University of Technology because of the complexity of simultaneous sampling and determining PCDFs, PCDDs, PCB and HCB. For the determination a GC-MS/MS system was used. RESULTS AND DISCUSSION: Results from the work indicate that the highest dioxins and PCB concentrations were recorded for iron ore sintering plants at 1.10-1.32 ng total1 TEQ/Nm3 followed by aluminium scrap melting at 0.03-0.66 ng total TEQ/Nm3. The highest HCB concentrations at 613-1491 ng/Nm3 were also recorded fo iron ore sintering plants, whereas at aluminium plants the HCB concentrations were in the range of only 10.1-22.7 ng/Nm3. CONCLUSIONS: The above investigations indicate that secondary aluminium production is the most significant dioxins source, if calculated as emission factor values. However, iron ore sintering plants are operating at much higher production capacity, causing this process to become the major source of dioxins, PCB and HCB pollution to the atmosphere in Poland. RECOMMENDATIONS AND PERSPECTIVES: Based on the performed tests and the environmental reviews of selected plants several recommendations were formulated for the reduction of generation or of emission of these pollutants from iron ore sintering plants, electric arc furnace steel production processes, hot-blast furnace operations, secondary aluminium smelting and primary zinc production from zinc cathodes. PMID- 17722768 TI - Toxicity of cobalt-complexed cyanide to Oncorhynchus mykiss, Daphnia magna, and Ceriodaphnia dubia. Potentiation by ultraviolet radiation and attenuation by dissolved organic carbon and adaptive UV tolerance. AB - BACKGROUND: Cobalt cyanide complexes often result when ore is treated with cyanide solutions to extract gold and other metals. These have recently been discovered in low but significant concentrations in effluents from gold leach operations. This study was conducted to determine the potential toxicity of cobalt-cyanide complexes to freshwater organisms and the extent to which ultraviolet radiation (UV) potentiates this toxicity. Tests were also conducted to determine if humic acids or if adaptation to UV influenced sensitivity to the cyanide complexes. METHODS: Rainbow trout (Oncorhynchus mykiss), Daphnia magna, and Ceriodaphnia dubia were exposed to potassium hexacyanocobaltate in the presence and absence of UV radiation, in the presence and absence of humic acids. Cyano-cobalt exposures were also conducted with C. dubia from cultures adapted to elevated UV. RESULTS: With an LC50 concentration of 0.38 mg/L, cyanocobalt was over a 1000 times more toxic to rainbow trout in the presence of UV at a low, environmentally relevant irradiance level (4 microW/cm2 as UVB) than exposure to this compound in the absence of UV with an LC50 of 112.9 mg/L. Toxicity was immediately apparent, with mortality occurring within an hour of the onset of exposure at the highest concentration. Fish were unaffected by exposure to UV alone. Weak-acid dissociable cyanide concentrations were observed in irradiated aqueous solutions of cyanocobaltate within hours of UV exposure and persisted in the presence of UV for at least 96 hours, whereas negligible concentrations were observed in the absence of UV. The presence of humic acids significantly diminished cyanocobalt toxicity to D. magna and reduced mortality from UV exposure. Humic acids did not significantly influence survival among C. dubia. C. dubia from UV-adapted populations were less sensitive to metallocyanide compounds than organisms from unadapted populations. CONCLUSIONS: The results indicate that metallocyanide complexes may pose a hazard to aquatic life through photochemically induced processes. Factors that decrease UV exposure such as dissolved organic carbon or increased pigmentation would diminish toxicity. PMID- 17722769 TI - Comparing domestic versus imported apples: a focus on energy use. AB - GOAL, SCOPE AND BACKGROUND: The issue of whether food miles are a relevant indicator for the environmental impacts associated with foods has received significant attention in recent years. It is suggested here that issues other than the distance travelled need to be considered. The argument is presented by illustrating the case for the provision of apples. MATERIALS AND METHODS: The effects of variability in primary energy requirements for apple cultivation and for other life cycle stages, seasonality (timing of consumption) and loss of produce during storage are studied in this paper, by comparing apples from different supplier countries for consumption in Europe. RESULTS: Data sources for primary energy use (PEU) of apple production are identified ranging from 0.4-3.8 MJ/kg apples for European and Southern American countries and 0.4-0.7 MJ/kg for New Zealand. This variability is related to different yields and producer management practices in the different countries. Storage loss may range from 5% to 40% for storage periods between 4 and 10 months, and this has a significant effect on the results (e.g. increasing the total PEU by 8-16% when stored for 5-9 months in Europe as compared with a no loss and no storage situation). The storage periods and related storage losses change markedly through the year for imported (i.e. non-European) versus European apples. DISCUSSION: The timing of consumption and related storage losses need to be included in the assessment, as this affects the order of preference for locally sourced versus imported apples. The variability in energy requirements in different life cycle stages, but particularly for the fruit production stage, is also significant in this comparative analysis. CONCLUSIONS: Overall, it seems that there are similarities in the total PEU ranges for European and New Zealand apples during the Southern Hemisphere's apple season (European spring and summer). However, during the European autumn and winter (Northern Hemisphere apple season) PEU values are generally higher for apples imported from the Southern Hemisphere compared with European apples consumed in Europe. However, this latter observation may not hold true where apples for consumption in one European country are imported from another European country, because energy use for road transportation has a significant influence on the result. RECOMMENDATIONS AND PERSPECTIVES: Future studies comparing alternative sources of fresh produce need to account for ranges of data for the fruit production and storage stages, which reflect the seasonality of production. PMID- 17722770 TI - Vertical distribution of acid-volatile sulfide and simultaneously extracted metals in mangrove sediments from the Jiulong River Estuary, Fujian, China. AB - BACKGROUND: Acid-volatile sulfide (AVS) is operationally defined as sulfides in sediment, which are soluble in cold acid, and is reported as the most active part of the total sulfur in aquatic sediments. It is a key partitioning phase controlling the activities of divalent cationic heavy metals in sediment. METHODS: In order to examine this in mangrove environments, six sites were selected along the Jiulong River Estuary in Fujian, China, which had previously been reported to be polluted by heavy metals. Sediments were sampled from 0-60 cm depth at each site, and the spatial distribution of AVS and SEM (simultaneously extracted metals: copper, cadmium, zinc, and lead) were determined. RESULTS AND DISCUSSION: The results indicate that the AVS concentrations had a spatial variation, ranging from 0.24 to 16.10 pmol g(-1) sediment dry weight. The AVS concentration in the surface layer is lower than that of the deeper sediment, with peak values in the 15-30 cm horizon. There was no correlation between the AVS value and organic matter content or total dissolved salts, but a significant positive correlation of AVS with surface sediment (0-5 cm) moisture content was found. This indicates that water logged sediments tend to have a high AVS value. The amount of SEM was within the range of 0.33-2.80 micromol g(-1) sediment dry weight and decreased with sediment depth. CONCLUSIONS: There was a marked variation in AVS and SEM among different sites studied. AVS concentrations were generally lower in the surface sediments, while SEM concentrations slightly decreased with the depth. Higher concentrations of SEM found in the upper layers of the sediments confirm the earlier suggestions that this study area may suffer from increasing heavy metal pollution. RECOMMENDATIONS AND PERSPECTIVES: When monitoring environmental impacts by using AVS, the micro and large-scale spatial variation as well as vertical distribution need to be estimated to avoid misleading results. Both AVS and SEM concentrations in different sediment layers should be taken into account in assessing the potential impact of heavy metals on the biotic environment, PMID- 17722771 TI - The mother of invention. A physician-owned medical group builds its own clinical decision support tool and brings it to the open market. PMID- 17722772 TI - Shift report redesign. A Midwest medical center uses server-based phone technology to streamline shift reporting. PMID- 17722774 TI - Going mobile--from square one. A bankrupted provider in New York gets reorganized and back on track with mobile charge-capture technology. PMID- 17722773 TI - Integrated ED. A Mississippi area medical center streamlines critical patient care through EDIS. PMID- 17722775 TI - Leading the charge to efficiency. Dana-Farber Cancer Institute's transition to electronic charge capture increases accuracy and enables online reconciliation. PMID- 17722776 TI - "To reach a representative, please click the icon". A Blue's call center Web based VoIP solution empowers providers and saves time. PMID- 17722778 TI - The key to improving the patient experience. PMID- 17722777 TI - Weathering the perfect storm. An examination of procedures intended to ensure consent is truly informed. PMID- 17722779 TI - [Frozen section: interest and limitations in cancer pathology]. AB - The utility of frozen section examination in the intra-operative management of patients with cancer is well established since the inception of the technique in the eurly part of this century. The aim of this review are to describe technical aspects, indications for and limitations of frozen section diagnosis in cancer surgery. Most common reusonsfor interpretative errors are discussed. The authors offred several recommandations for surgeons and patholgists wich will optimize the clinical utility of intra-operative consultation. PMID- 17722780 TI - [Predictive factors of recurrent hemorrhage in duodenal ulcer: report of 208 cases]. AB - The aim of this study was to evaluate clinical, biological and endoscopic predictive factors of recurrent bleeding. Two hundred and eight patients (169 males/39 females) with a bleeding from duodenal ulcers, confirmed by an endoscopy, were included in a retrospective study performed over 3 years. Forrest classification was used to describe endoscopic stigmata of bleeding. Those who are Forrest la and lb were directly operated. Twenty two patients (10,5%) had rebled. Based on bivariate analysis, the predictive factors of recurrent bleeding were the site of ulcer, a shock at admission, ulcer size D 2.0 cm and the presence of stigmata of bleeding (Forrest II) p<0,05. Only endoscopic stigmata of bleeding and shock were predictive factors of recurrent bleeding in multivariate analysis. Mortality with 2.4% of rate, was strongly linked with recurrent bleeding in elderly and ill people. PMID- 17722781 TI - [Breast cancer in elderly women in Tunisia. Retrospective study of 106 patients older than 65 years]. AB - OBJECTIVE: To report the epidemiological profile, anatomo - clinic, prognostic and therapeutic of breast cancers in aged woman from the region of the Center of Tunisia. Our retrospective study concern 106 patients with mammary cancers treated between January 1990 and December 1997 at the Farhat Hached Hospital in Sousse (Tunisia). The mean age was 71 years (extremes 65-91), 66% of the patients had an age more than 75 years, the mean age at the menopause was of 50 years. The size middle clinic was of 50 mm, 45.3 % of tumors was classed T4, 39.6 % T3. 39.6% of patients have a clinical axillary adenopathis. 14.2% of patients have metastases at diagnostics. 62.5% of the cases have a high histo-pronostic grading. The prognostic factor analysis recovered in multivary survey two parameters significatifs for the survival: the size tumoral (p <0.005) and the presence of metastases at the time of the diagnosis (p <0.001). The biologic and evolutionary features of the cancer of the breast in the aged woman bring to consider the hormonal approach like the most logical, especially for the patients bearers of hormonosensibles tumors, of or the interest of the systematic dosage of the hormonal receptors. PMID- 17722782 TI - [Idiopathic nephrotic syndrome in children: report of 57 cases]. AB - The aim of this study was to analysis epidemiological, clinical, biochemical and histopathological profile of INS in children and to document their management and their final course. A retrospective study of 57 children with INS hospitalized in the pediatric department of Monastir hospital from the 1st of January 1989 to the 31 th of December 1999 was conducted. The annual rate was of 3,2 cases 1000 admissions, sex ratio was of 1,28 with 32 boys and 25 girls. The mean age at the onset of the affection was of 5 years and 3 months. The renal biopsy was performed in 18 children. The histological finding were a minimal change histology in 50% of cases, a focal segmental glomerulosclerosis in 33% of cases and membrano-proliferative glomerulonephritis in 11% of cases. A cortico-therapy was initiated in all children. 87,5% of them were steroid sensitive. 22,4% of patients had steroid dependent nephrotic syndrome and 12,5% of patients had steroid resistant nephrotic syndrome. All children steroid resistant underwent immunosuppressive therapy; however chronic failure was observed in 57% of them. After a mean follow up period of 46 months, recovery was obtained in 48,2%, complete remission in 28,5% and death in 5,3% of cases. PMID- 17722783 TI - [Isolated fetal pyelectasis: pathologic significance and therapeutic implications]. AB - We report a retrospective study of nine neonatal observations of antenatal isolated pyelectasis during a period of two years. Pyelectasis associated with other congenital abnormalities and in utero died foetus were excluded. Finding interesting sex, gestational age at diagnosis, echographic aspect, antenatal management and postnatal follow-up were assigned. Foetal kidneys was noted in two cases and an oligoamnios was noted in two other cases. No foetal urinary intervention was assessed. Postnatal exploration revealed a transitional pyelectasis in four cases, an ureteropelvic junction obstruction in four cases and a congenital megauretere in one case. Postnatal renal function was decreased in two cases. Postnatal surgery was assessed in two cases and a spontaneous regression under a sequential treatment occurred in the other three cases. Isolated foetal pyelectasis can have a pathologic significance.This examination permits, in plus, to evaluate the renal prognosis. Antenatal therapeutic implications of interruption of pregnancy or urinary intervention are still not clear and those after birth depend essentially on renal function determined by scintigraphy. PMID- 17722784 TI - [Acute severe asthma in infants. Study of 34 cases]. AB - Acute severe asthma is the most severe acute complication of infant asthma. The aim of our study was to specify its characteristics in the Tunisian infant and analysis his initial medical care. It is a retrospective study included 34 infants less than 3 year old, admitted during the period from January 1, 1995 to December 31, 2000. The acute severe asthma was induced by a respiratory viral infection in 80 % of cases. The delay hospitalisation was upper than 48 hours in 56 % of the cases. Before admission, corticosteroids were not instituted in 84 % of the cases. The initial examination noted neurological disorders in 52 % of cases and hemodynamic disorders in 8 % of cases. All patients received beta2 adrenergic and intravenous corticosteroids. Intravenous aminophylline was used in 68 % of patients. Mechanical ventilation was necessary among 6 patients. The evolution was complicated: pneumothorax (3 cases), hypokaliemia (3 cases), inappropriate secretion of ADH syndrome (1 case). There were 2 deaths. Acute severe asthma forces a correct evaluation of the severity of the asthmatic disease in order to adapt the long-term therapy. PMID- 17722785 TI - [Attitude to cervical cancer screening of women residing in two regions of northern Tunisia]. AB - The objective of this survey to describe knowledge, attitudes and behaviours of women residing in two regions of the North of Tunisia, towards cervical cancer screening methods. 936 women residing to the Ariana (urbanized region) and 993 women residing to Zaghouan (region to farming predominance) were included; they were chosen according to the method of quotas while taking like criteria's, the of area residence (urban or rural), age and the level of education. Every woman should have answered to a questionnaire. Data collected were related to women perception of the severity of the cervical cancer, of their vulnerability for this cancer, of screening efficiency and the recourse of women to this service. The recourse to the cervical cancer screening was significantly more frequent in Ariana (24,6% vs. 13,8% p <0,001); the half of women is optimistic towards the therapeutic progress recorded in Tunisia in the domain of cancer. A better organization of cervical cancer screening including the individual invitations of women and a better sensitization and implication of physicians of the first line in the two sectors public and private, are indispensable to improve the frequency of recourse to cervical cancer screening. PMID- 17722787 TI - [Tuberculous thoracic parietal abcess. Report of 4 cases]. AB - Cold abcess of the chest wall is a rare extra-pulmonary tuberculous location, usually described in cases of severe or disseminated form of tuberculous. His frequency is estimated for 1 to 5% of osteoarticular tuberculous. Four cases of cold abcess of the chest wall are reported. Three of the patients are more than 65- year- old and a 30-year-old woman. In three cases, abcess is developped in the posterior chest wall and it is sternal in the fourth case . Neither immunodepression nor previous tuberculous history or other location of the tuberculosis were noted. Diagnosis is based on demonstrating mycobacterium tuberculosis in pus culture in three cases and on histologic pattern in the last one. Classic anti-tuberculosis treatement was prolonged at 12 and 15 months in 2 patients because of respectively general and local prolonged evolution. PMID- 17722786 TI - [Persistent forms of cow's milk allergy. Report of 6 cases]. AB - BACKGROUND: Cow's milk allergy is defined as reproducible adverse reaction to a food protein antigen which is immune medieted. About 80 to 90 % become clinically tolerated within the first three year of live. The aim of this study is to evaluate the clinical, immunological and evolutive characteristics of the 10 % to 20 % of persistent form of cow's milk allergy. METHODS: This study included six persistent form of cow's milk allergy (2 boys and 4 girls). The provocation challenge test according to Rance recommendation, have been made from 6 months to one year. RESULTS: 4/6 infants with persistent cow's milk allergy have an atopic familial disease. Clinical presentation changed over time at once symptoms were preventely gastrointestinal, at the end there was an increased frequency of atopic disease (asthma: 4/6 infants) CONCLUSION: Persistent form of cow's milk allergy are characterized by considerable importance of familial atopic disease; change in cow's milk allergy manifestations over time and more prolonged delay between cow's milk persistent consumption and manifestations of symptoms. PMID- 17722789 TI - [Particular evolution of the thyroid state in Grave's disease: two cases]. AB - We report two cases of Grave's disease (GD) caracterized by the succession of hypothyroid and hyperthyroid states. Case 1: A 32 years old woman, has presented initially a typical GD with hyperthyroidism. Grave's ophtalmopathy and homogenous goiter. Four months later, she presented a spontaneous hypothyroidism necessiting treatment with thyroxine and a severe myasthenia gravis. More later (6 months), she experienced symptoms of hyperthyroidism after thymectomy. The level of anti thyrotropin-receptor antibodies (TSab) was very high (141 UI/I, NV < 10). Case 2: A 29 years old woman has been treated by thyroxine (150 microg/day) for a primary hypothyroidism. Ten months later, she presented symptoms of hyperthyroidism even after stoppage of thyroxine. TSH value was decreased (TSH < 0.05 microU/ml) and FT4 level was raised (FT4 = 25.5 pmol/l). The thyroid antibodies were positive. We discuss, after review of the litterature, the physiopathological mecanisms of these changes in the thyroid state, particularly the role of the blocking and stimulating anti-thyrotropin-receptor antibodies. PMID- 17722788 TI - [Recurrent bilateral shoulder hand syndrome induced by phenobarbital]. AB - Algodystrophy syndrome is characterized by pain, vasomotor disorders and/or trophic skin changes, without laboratory signs of inflammation. Among the etiological factors of this syndrome (trauma, cerebrovascular accident, diabetes mellitus...), iatrogenic ones including phenobarbital can be observed. We report a case of phenobarbital induced recurrent bilateral shoulder-hand syndrome in a 67 years old women with hypertension, diabetes, and history of epileptic crisis following ischemic cerebrovascular accidents. The patient recovered after barbiturate withdrawal and treatment with calcitonin. It's necessary to diagnose promptly shoulder-hand syndrome of iatrogenic cause in order to withdraw definitively the responsible drug, to start an effective therapy, at this stage, on pain and bone demineralization and to prevent severe sequels. PMID- 17722790 TI - [Plexiform fibrohistiocytic tumor: a low grade malignancy lesion]. AB - The plexiform fibrohistiocytic tumor is rare. It affects mainly children and adolescent. This tumor occurs at the dermo-subcutaneous region of the upper extremities. We report a case of a 11 year-old child exhibited a nodule on his forearm who is diagnosed as a plexiform fibrohistiocytic tumor. Histologically, it was a plexiform proliferation of spindle fibroblast-like cells associated with mononuclear histiocyte-like cells. Treatement consisted on a large excision and in the follow-up there is no recurrence of the tumor. 'I'he differential diagnosis may be difficult with other tumors in to the derm or sub-cutaneus adipose tissu, having a plexiform pattern or a predominantly fibroblastic pattern like the fibromatosis and well differenciated fibrosarcoma. This tumor reccured in 20 to 30 % of the cases. Lymph node and pulmonary metastasis are rare. This clinical behaviour leads authors to class it into a "borderline tumor". PMID- 17722791 TI - [Role of mitochondrial dysfunction in non-alcoholic steatohepatitis]. AB - The non alcoholic steatohepatitis is a more and more frequent disease. Great progress in the physiopathologic mechanisms has been recently observed. The mitochondrial dysfunction seems to be the main mechanism implied in the necroticoinflammatory genesis of the non alcoholic steatohepatitis lesions. When this one is of metabolic origin, this dysfunction occurs on a vulnerable to aggressions steatosis liver. Several implied factors leads to the increased liberation of free radicals that will activate the lipidic peroxydation. This one is considered as the main generator of necroticoinflammatory lesions and fibrosis. The future therapeutic alternatives depends on a better comprehension of mitochondrial dysfunction. PMID- 17722792 TI - [Bronchiectasis in rheumatoid arthritis. High resolution computed pulmonary tomography]. AB - To evaluate the prevalence of bronchiectasis in rhumatoid arthritis (RA) we have study thirty patients (24 women and 6 men), with a mean age of 45,2 years. All patients have a RA with a follow up of 5,84 years, positive rhumatoid factor were found in 22 cases. All patients have had high resolution computed pulmonary tomography, study of clinical, radiological and spirometry parameters. Bronchiectasis was found in 5 cases (16,6%) and is the most frequent abnormality found. These bronchiectasis are associated to an interstitial syndrome (2 cases) and pleural node (1 case). We don't find any significant difference in rhumatoid factor, extra-articular involvements, respiratory manifestations, smoke use or spirometry parameters between the sub group with or without bronchiectasis. PMID- 17722793 TI - [Epidemiological features of patients hospitalized in coronary care units at the military hospital, Tunisia, for 1994-1998: preliminary results]. AB - The aim of this study was to evaluate the frequency of cardiovascular disease and risk factors associated in patients hospitalised in coronary care units at Military Hospital, Tunis, over the period 1994-1998. The clinical features of 3513 patients (2389 men and 1124 women) on hospital admission were analysed. 47.3% of patients were hospitalised for coronary disease, 12.5% for valvular heart disease, 5.2% for cardiomyopathy, 16.2% for arrhythmia and conduction disturbance, 6.4% for hypertension and 12.2% for other pathologies. With this risk factor profile Tunisia has to implement a national strategy of primary prevention and heart heath promotion in addition to the efforts recently made in secondary prevention of some chronic disease such as hypertension and diabetes. PMID- 17722794 TI - [Acute polyradiculoneuropathy. Guillain-Barre syndrome]. AB - A retrospective study of 120 cases of acute polyradiculoneuropathy hospitalized in the National Institute of Neurology, since 1974. We analysed the clinical and neurophysiological pictures, the course of the disease and the prognosis. All ages and sex were affected. The mean age of onset was 34 years. There were a predominance of male 2.5:1. Weakness, particularly of the lower limbs, was the initial complaint of patients. A rise in the level of cerebro-spinal fluid protein in the absence of pleiocytosis was found in 80% of patients. Electrophysiological data showed most frequent sensory motor demyelinating polyradiculo-neuropathies (60%). Conduction blocks were found in 90% of cases. The last 6 years, gammaglobulin (0.4g/kg per day for 5 days) was given for the first days of the disease and has been shown to improve the vital and functional prognosis. PMID- 17722795 TI - [Patient flow analysis in seven primary health care centers in Monastir (Tunisia)]. AB - Patient flow analysis was considered as a part of work organisation in primary health care center which led to quality and patient satisfaction. From 14 January to 6 march 1998 we conduct a research in the 7 PHC of Monastir health district to describe PFA and to detect bottlenecks in this flow. The median waiting time to see the physician was 1h 24 mn, 5 mn for care and 4 mn the contact with the physician. Thus only 15.42% of median stay time, 1h 41 mn, was used by patient. PMID- 17722796 TI - [The place of endoscopic sphincterotomy in the treatment of acute biliary pancreatitis: report of 78 cases]. AB - In this retrospective study, 78 patients with acute biliary pancreatitis underwent endoscopic retrograde cholangio-pancreatography (31 men, 47 women; median age 61 years). It was a severe pancreatitis in 70% cases. The median time from admission to endoscopic sphincterotomy was 4 days. Endoscopic sphincterotomy was performed in 73 patients (93.3%). Bile duct clearance was achieved in 69 patients (88.37%). Overall, the complication rate was 7%. All the patients recovered after endoscopic sphincterotomy. Surgery was necessary in 40% cases. PMID- 17722797 TI - [Functional outcome after resection followed by a coloanal anastomosis for cancer of the rectum]. AB - The aim of the study was to asseses the operative, functional results of total proctectomy with coloanal anastomosis (CAA). Between 1990 and 2002, 24 patients (14 males and 10 females ) with a mean age of 50,6 years were operated on for cancer of the rectum and they underwent a total proctectomy with CAA. There was one operative death. 3 patients developed non specific complications. 4 patients experienced a supra anastomosis stenosis and underwent a new straight CAA Functional outcome were evaluated by a scoring system fonction and were considered good in 87 and 84% at 1 and 2 years respectively. Low anterior resection combined with CAA provides good treatment for mid-rectal cancers and for some distal rectal cancers. It had a good functional outcome. However Both procedures and selection of patients who underwent radiotherapy must be carefully performed. PMID- 17722798 TI - [Adult granulosa cell tumors of the ovary. Report of 32 cases]. AB - The aim of this study is the analysis of different epidemiological, clinical, paraclinical and therapeutic aspects of adult granulosa cell tumors of the ovary (AGCT) GCT accounts for 5.7% of all ovarian malignancies. Echography objectives pelvic tumor in all cases. Diagnosis was histological. Primary treatment was exclusively surgically in 11 cases, followed by chemotherapy in 19 cases and radiotherapy in 2 cases. Patients with stage Ia who desire further childbearing can be treated with unilateral adnexectomy. For all other cases, radical surgery followed by chemotherapy for advanced stages and recurrences is the treatment of choice. Prognosis is tightly depending on stage and histologic finding. PMID- 17722799 TI - [Pulmonary aspergillosis in a child with chronic granulomatous disease]. AB - The chronic granulomatous disease is characterised by the occurence of multiple bacterial and fungal infections since the early childhood. This susceptibility to infections must be prevented by a primary prophlylaxis against the opportunistic germs like pneumocystis and aspergillus. Our case is about a twelve-year-old boy who had a prophylaxis since his fourth month of life. At 10 years he presented a pleuro-pneumonia refractory to a large spectrum antibiotherapy. The aspergillar etiology was established on clinical, radiological and serological arguments. An amphotericine B treatment allowed a good clinical and radiological outcome of this pleuro-pulmonary affection. However, a dorsal spondylodiscitis complicated the course of the disease. A secondary vertebral aspergillosis or a Pott's disease were suspected. The vertebral bipsy was'nt conclusive. The association of antituberculous and antifungal agents with adjuvant molecules (IFN, granulotic transfusions and GM-CSF) permitted a good clinical outcome and the stabilisation of the radiological lesions. PMID- 17722800 TI - [Testicular epidermoid cyst. A case report]. AB - Epidermoid cyst of the testis is a rare, begnin intratesticular tumor. Through a case report of a patient who underwent an orchidectomy, we study clinical, radiological and therapeutic aspects and particularities of this pathology. PMID- 17722801 TI - [Vertebroplasty success in a case of aggressive hemangioma]. AB - Vertebral hemangioma is a vascular tumor most oftenly asymptomatic and of casual radiological discovery. More rarely, it can be aggressive, causing neurological complications and therefore requiring a convenient and sustained therapy where vertebroplasty is of essential importance. In this context, we report a case of an aggressive vertebral angioma of L4 which was responsible for lumbocruralgy. She underwent verterbroplasty and then had a very good outcome. In this way we deal with the the different technics of vertebroplasty, their advantages compared to other therapeutic medical, and or surgical methods, as well as their complications. PMID- 17722802 TI - [Embolic pseudotumor diagnosed by surgery]. AB - We report a case of pulmonary infarction in a 72-year-old woman who was hospitalised for hemoptysis, chest pain and weight and coin a lesion in the loss periphery of the left lower lobe. Camputed tomography of the chest demonstrated a sub pleural solitary nodule with spicular radiation. Video-assisted thoracoscopic surgery was performed to obtain a histological diagnosis. Thoracoscopic examination showed a lesion that evoked chronic abscess. Histological examination confirmed an ischemic infarction. This is the second case of pseudotumor due to pulmonary infarction that was diagnosed by video-assisted thoracoscopic resection. PMID- 17722803 TI - [Isolated splenic metastasis revealing colon cancer]. AB - Splenic metastasis of colon cancer is uncommon especially when isolated. In fact, they are usually associated to multi visceral location. Malignant melanoma, cancer of breast and lung and ovarian carcinoma are the most common cancer which metastases in spleen. Splenic metastasis of colon cancer is rare and exceptionally isolated. Ten cases of isolated splenic metastasis in colon cancer are reported in literature. We report a new case of intra splenic kystic metastasis revealing an asymptomatic sigmoid cancer in a 63 years old patient. PMID- 17722804 TI - [Malignancy arising in seborrheic keratosis: two cases report]. AB - Seborrheic keratosis are one of the most common benign epidermal tumors encountered in clinical practice. Malignant transformation is exceptional. It may occur by the involvement of human papilloma virus. We report two cases of seborrheic keratosis in respectively 58 and 60-years-old women, which, on biopsy, revealed the presence of Bowen's disease for the former and Squamous cell carcinoma for the later. PMID- 17722805 TI - Self medication practices among workers in a tertiary hospital in Nigeria. AB - Studies in most developing countries revealed (70-95%) of illnesses are treated through self medication. Poor accessibility to medical services have been associated with this practice. This study determines the pattern of self medication among workers at the University College Hospital, Ibadan, Nigeria. In a cross sectional study, workers were selected using a stratified random sampling technique. A high proportion of workers (73%) reported the practice of self medication and 95.6% of them correctly use appropriate drugs. About 80% of these workers stock their drugs at home. Also, 80.4% procure their drugs in chemist shops. A higher proportion of workers directly involved with medical care services (90.9%) practice self medication compared to those involved with non medical care services (62.9%), P < 0.01. Also, the higher the education of workers the more is the proportion that practice self medication. (P < 0.05). Self-medication is commonly practiced among the hospital population who have relatively easy access to medical care services. Thus self medication may be a real health option. PMID- 17722806 TI - Validation of a Yoruba translation of the World Health Organization's quality of life scale--short form among stroke survivors in Southwest Nigeria. AB - The World Health Organization's quality of life scale - short form (WHOQOL-BREF) is a well-validated, cross-cultural tool for measuring quality of life (QOL) of patients with chronic diseases. It has been translated into over 20 languages, none of which is an indigenous Nigerianlanguage. The aim of this study was to investigate the validity of a Yoruba translated version of the WHOQOL-BREF Yoruba is the indigenous language of southwestern Nigeria. The English version of the WHOQOL-BREF was translated into Yoruba and it went through two rounds of back translation. The English and Yoruba versions of WHOQOL-BREF were completed by 41 stroke survivors, literate in both languages. Participants were recruited through purposive sampling method from physiotherapy clinics of all tertiary health institutions in southwestern Nigeria between April and August, 2004. Data was analyzed using Spearman rank order correlation and paired t- test with the alpha level set at 0.05. Participants (24 males, 14 females) were aged 55 +/- 10.7 years and have had stroke for 28.4 +/- 6.7 months. Participants' domain scores on the Yoruba translated version of WHOQOL-BREF correlated significantly with those on its English version (r = 0.695-0.859; p = 0.000). This Yoruba version is a valid translation of the English WHOQOL-BREF and may be used for assessing QOL of stroke survivors in southwestern Nigeria. PMID- 17722808 TI - Study processes of first year clinical students of the College Of Medicine, University of Ibadan, Ibadan Nigeria. AB - Students adopt several learning approaches towards achieving the perceived goal of passing their prescribed examinations. This study was carried out to determine the study processes being used by medical students of the College of Medicine, University of Ibadan on arrival at the Faculty of Clinical Sciences. One hundred and sixty five first year clinical students were studied using the modified 'Biggs' Study Process Questionnaire. Additional questions to identify local factors that would contribute to the learning were also included. There were 143 respondents (87% of the study population). The predominant study pattern among the students was the deep approach (63%). The achieving and superficial approaches were used by 8% and 29% of the students respectively. Additional analysis showed that 68%, 31% and 1% had 'good', 'average' and poor learning capacities respectively. Self interest was the principal reason why the students chose medicine as a career. Most students (76%) preferred lectures to tutorials, and only 30% found out extra information about topics taught frequently. Thirty nine percent of the study cohort saw their teachers as role models, and 76% intended to travel abroad after graduation. Majority of 1st year clinical students of the College of Medicine, University of Ibadan adopted a deep approach to learning and have a good capacity to learn. However, most do not employ self directed learning strategies and do not see their teachers as role models. The majority intend to travel abroad upon graduation. PMID- 17722807 TI - Quinine lowers serum and testicular testosterone in adult Sprague-Dawley rats. AB - We have earlier demonstrated that quinine (QU) is a testicular toxicant. This present study was aimed at evaluating the effects of QU on both the serum and testicular levels of testosterone (TT) in an attempt to elucidate one of the potential mechanisms of QU-induced testicular toxicity. Thirty adult male Sprague Dawley rats weighing 180-200g were used and were randomly divided into 3 groups of 10 rats each. Rats in group 1 had distilled water. Rats in group 2 had QU only at the dose of 10 mg/kg body weight per day (5 days in a week) for 8 weeks. Rats in group 3 rats had 10 mg/kg of QU (5 days in week) and 0.05 mg/kg of TT (3 days in a week) for 8 weeks. All the animals were sacrificed at the end of 8 weeks by decapitation. Seminal analysis was done on the tubular fluid aspirated from the caudal epididymides. The two testes were excised, weighed, and volume estimated. One testis of each rat (0.25 g of tissue) was homogenized with Potassium Chloride and TT level determined in the supernatant of the homogenate, while the other testis was processed for histology. Morphometry was carried out by assessing the diameter, cross-sectional area, number of profiles per unit area, length density and numerical density of the seminiferous tubules, and the relative and absolute volume of testicular components. The serum levels of TT in all the animals were also determined at the time of sacrifice. Both the serum and testicular levels of TT in rats administered QU only were significantly (P < 0.001) lower than those of the control and QU plus TT-treated rats. We conclude that QU induces spermatogenic epithelial toxicity by possibly interfering with the steroidogenic function of the Leydig cell. PMID- 17722809 TI - Plasmid determined resistance to quinolones in clinical isolates of Gram-negative bacilli. AB - A total of 166 strains of Gram-negative bacilli comprising 65 Klebsiella species, 22 Escherichia coli, 39 Pseudomonas aeruginosa, 20 Proteus species, 18 other Pseudomonas species and 2 Salmonella typhi, were isolated from clinical specimens in the University College Hospital, Ibadan. Antimicrobial susceptibility testing and plasmid profiling of the strains were done. Ceftazidine had the highest antibacterial activity of 83.1% compared to the fluoroquinolones followed by ciprofloxacin (78.3%), pefloxacin (69.9%) and ofloxacin (56%) respectively. Of the 166 strains, 44 were found to be resistant to most of the antimicrobial agents tested. Resistance to ofloxacin was common among the resistant strains. The resistant strains harboured plasmids with molecular sizes ranging from 6.6kb to 17.4kb and were grouped into five plasmid profile groups. Transformation experiment showed that 59.2% of the resistant strains carried a common R-plasmid of size 10.7kb. Resistance to ciprofloxacin and pefloxacin were found to be plasmid borne. PMID- 17722811 TI - Knowledge and perception of stroke among adults in Osogbo, Nigeria. AB - Stroke is a major cause of neurological admission in Nigeria. Its prevention has been reported to be dependent on public knowledge of stroke warning signs and risk factors. Ignorance of stroke risk factors and inability to control such risk factors may contribute to high prevalence of stroke among blacks. This cross sectional descriptive study therefore investigated knowledge and perception of stroke among adults living in Osogbo, Nigeria. Multistage sampling technique was used to select a sample of 900 adults aged between 18 and 80 years as at their last birthday. Data were collected using a pretested modified version of instrument used in a previous study. Data collected from the final survey instrument were analyzed using both descriptive and inferential statistics. A total of 900 adults with male to female ratio of 1.4:1 and mean age 43.6+/-17.63 years participated in this study. Four hundred and seven (45.2%) of the interviewees reported that they were hypertensive. Heart was incorrectly identified by 54% of the respondents as injured organ during stroke. Majority (83.0%) of the respondents indicated that stroke was preventable whereas only 37.1% of them were aware of stroke recurrence. The most common stroke risk factors listed by the respondents were hypertension (78.2%) stress (59.9%) and old age (58.3%). Stroke survivors were perceived by 68.7% of the respondents as being able to return to activities of daily living but with diminished quality of social life. Knowledge of stroke warning signs and risk factors was good among the respondents. However, their baseline knowledge about stroke was poor. Stroke survivors were perceived as being unable to return to pre-stroke's quality of social life. Development of educational strategies to enlighten the public about stroke is therefore recommended. PMID- 17722812 TI - Pre-donation screening of intending blood donors for antibodies to infectious agents in a Nigerian tertiary health institution: a pilot study. AB - Large pools of blood donors are difficult to get in most donor centres in Nigeria; donors come in trickles and only when there is pressing need. Predonation screening for transmissible agents, using induvidualised rapid screening techniques is often employed to avoid wastage of blood bags and reagents. The aim is to compare the relative prevalences of serum markers of infectious diseases in intending blood donors before blood donation for the purpose of elimination. Both paid and volunteer blood donors were screened for HIV, HbsAg, and HCV antibodies using the rapid test kits. The presence of microfilaria in blood and low haematocrit were also checked for. Prospective donors were initially sorted using a structured questionnaire on risk behaviour and were physically examined. Screenings were done before bleeding them. A total of 1259 donors were screened during the six-month duration of the study and 151 (12%) were rejected. Seropositivity for HBsAg in 69 (5.48%), HCV in 56 (4.45%), HIV in 9 (0.71%) were responsible for the rejection. Fourteen (1.1%) were rejected because of low haematocrit, while two (0.16%) others were not bled because of circulating microfilaria. We conclude that hepatitis viruses were responsible for most cases of donor rejection in Nigeria, post-donation screening for infectious agents lead to wastage of blood bags, problems of decontaminating and discarding infectious blood, and the loss to treatment and follow-up of infected persons who are likely to continue to spread the infectious agents. We therefore suggest pre-donation screening of prospective donors in blood banks. PMID- 17722810 TI - Effect of hyperglycemia on the efficacy of morphine analgesia in rats. AB - The effect exerted by hyperglycemia on the analgesic potential of morphine was studied in female Wistar rats with the hotplate device and the formalin test. Hyperglycemia induced by an intraperitoneal (ip) injection of alloxan (40mg/Kg) significantly (p < 0.05) reduced the potency of morphine in the two tests employed. While morphine caused an inhibition of 48.64% (44.83 +/- 3.69s vs 30.16 +/- 4.12s) in the pain sensitivity of control non-diabetic animals using the hotplate device, an inhibition of only 36.25% (31.50 +/- 2.28s Vs 23.12 +/- 1.80s) was recorded in the pain sensitivity of the diabetic group using the same method. In the formalin test, morphine inhibited the pain sensitivity by 35.23% (1.93 +/- 0.17 Vs 1.25 +/- 0.21) in the control non diabetic group and by 25.93% (2.16 +/- 0.09 Vs 160 +/- 0.15) in the diabetic group. From these data, it is hypothesized that the hyperglycemic state is responsible for selectively affecting the potency of morphine. These results, if found to be true in man, may have clinical implications for the use of morphine in diabetic subjects. PMID- 17722813 TI - Human immunodeficiency virus-associated tuberculosis: pattern and trend in the University of Ilorin Teaching Hospital. AB - To define the incidence and spectrum of extra pulmonary tuberculosis (EPTB) and the trend of pulmonary tuberculosis (PTB) among human immunodeficiency virus (HIV) infected patients in the University of Ilorin teaching hospital, a tertiary care centre in Nigeria. Review of all PTB cases diagnosed by Ziehl-Neelsen staining technique and EPTB diagnosed by tissue histology and/or cytology between January 2000 and December 2004. HIV/TB coinfection occurred in 40% (297 cases) of the 744 new cases of tuberculosis (TB) seen in the last 5 years, HIV/PTB occurred in 79% and HIV/EPTB occurred in 21%. About 47 new cases of HIV/PTB and 12 of HIV/EPTB were diagnosed per year. Tuberculous pleurisy with effusion; 23%, tuberculous meningitis; 16% and genital tuberculosis; 10% as (tuberculous: orchitis, endometritis and frozen pelvis) were common form of extra pulmonary presentation. The chance of mixed presentation was 3 times higher amongst the HIV positive than HIV negative patients; 27 vs. 11: X2 = 6.99, OR 3.25; 95% CI = 1.32 8.14, p-value = 0.008. Similarly the chance of miliary tuberculosis was 4 1/2 times higher in the HIV positive group; 9 vs. 2: X2 = 4.29, OR 4.67; 95% CI = 0.90-45.93, p-value = 0.03. Both conditions recorded the lowest CD4+ cells count; 88 cells/ul and 93.6.6 cells/ul, thus serving as features of advanced HIV illness. PTB and EPTB are common amongst the HIV infected patients; miliary spread and mixed presentation are signs of severe immunosuppression. PMID- 17722814 TI - Determination of trace elements status of Nigerians with sickle cell anaemia using INAA and PIXE. AB - The clinical application of trace elements in the management of Sickle Cell Anaemia (SCA) has not become standard recommended practice despite decades of research. A major reason for this is the ambivalence in published results as to the relative importance of some of these elements in the disease. An attempt has been made in this work to correct some of the various factors that could contribute to such inconsistencies. Results from separate investigations carried out on Nigerian subjects by our group, using both INAA and PIXE methods have been holistically evaluated and compared. Trace and minor elements were determined in wholeblood, erythrocytes, plasma, headhair and nail obtained from SCA patients in steady state and compared with identical samples from normal controls. Twelve elements were determined in blood while 20 and 30 elements were analysed in nail and hair samples respectively from the total 225 subjects. The results indicate a general mild zinc deficiency, more serious for males, in Nigerian SCA patients. It is clear that the elements Na, K, Rb and Br play key roles in maintaining homeostasis in the steady-state SCA patients. Possible gender influence in the utilization of K, Br and Fe in SCA is also suggested. PMID- 17722816 TI - Pulmonary tuberculosis in Ibadan: a ten-year review of laboratory reports (1996 2005). AB - Tuberculosis (TB) control programme is a balance between accurate diagnosis of the disease and effective treatment of cases to eliminate the disease in the community. We carried out a retrospective review of the specimens processed in the TB laboratory of the Department of Medical Microbiology, University College Hospital, Ibadan between 1996 and 2005. Majority of the specimens processed were sputum (75.2%) while cerebrospinal fluid and aspirates from other sources accounted for 4.3% and 20.5% respectively. Of the sputum processed, 2,738 (62.4%) were from male patients while 1,650(37.6%) were from female patients giving a male to female ratio of 1.66:1.00. Only 380 (9.5%) were reported smear positive while 477 (10.9%) were positive for culture. Three hundred and four (6.9%) were smear negative but culture positive while 207 (4.7%) were smear positive but negative for culture. Those sputum that were missed by smear microscopy (6.9%) were only confirmed by culture after six to eight weeks incubation. This culture method is only available in few reference centers in Nigeria. Thus, undiagnosed cases resulting from inadequate diagnostic facilities contribute an impediment to TB control efforts in the community. Hence there is an urgent need to have more accurate, affordable tools that would be available for use at the all levels of health care to achieve total eradication of TB in the community. PMID- 17722815 TI - Serum and seminal plasma hormonal profiles of infertile Nigerian male. AB - Male infertility constitutes a worldwide problem, especially in Nigeria where most men do not readily accept that they may contribute to the couple's infertility. In order to assess hormonal disturbances in the male infertility we compared male reproductive hormonal levels in human serum and seminal plasma and evaluated the hypothalamic-pituitary-testicular-axis in infertile Nigerian males. The biophysical semen parameters were assessed by W.H.O. standard manual method. Serum and seminal plasma male reproductive hormones (Leutinizing hormones, Follicular stimulating hormone, Prolactin and Testosterone) were measured by Enzyme Immunoassay (EIA) technique of W.H.O. in sixty (60) infertile adult male Nigerians (Oligospermic; n = 40 and azoopermic; n = 20) and forty controls of proven fertility (Normospermic subjects; n = 40). The results show that the serum concentrations of gonadotropins (LH and FSH) were significantly higher (P<0.05) in infertile subjects than controls. Patterns of serum prolactin levels were similar. The values of gonadotropins in serum were significantly higher (P<0.05) than those of seminal plasma. Seminal plasma testosterone in infertile subjects was significantly higher (P<0.005) than that of controls but the serum levels of testosterone were significantly higher (P<0.05) in azoospermic than oligospermic subjects and controls. There was no significant correlation between serum hormonal level and seminal plasma hormonal level in all the groups (P<0.05). We concluded that male infertility in Nigerians is characterized by hyperprolactinaemia, raised serum gonadotropins (LH, FSH), and raised seminal plasma testosterone. Hormonal profiles in serum and seminal plasma were not significantly correlated, and hence cannot be used as exclusive alternative in male infertility investigations. The observed spermogram in spite of significant elevation of seminal plasma testosterone in infertile males investigated suggests Sertoli cells malfunction. PMID- 17722817 TI - Prevalence and surgical morbidity of impacted mandibular third molar removal in the aging population: a retrospective study at the Lagos University Teaching Hospital. AB - Prophylactic surgical extraction of impacted third molars is not an uncommon practice in Europe and America. This has been justified on the basis that the risk of surgical morbidity increases with increasing age among other reasons. The purpose of this study is to report the prevalence of impacted third molar extraction and associated morbidity in patients = 40 years of age in our institution. A retrospective review of patients = 40 years of age who required surgical extraction of their impacted third molars between April 2001 and March 2006 at the Lagos University Teaching Hospital was carried out. Data collected included patients' age and sex, tooth/teeth extracted, indication(s) for tooth/teeth extraction, types of impaction, and surgical morbidity (intra-and postoperative complications). A total of 6.3% of patients requiring third molar surgical extraction were 40 years or older. No intraoperative complications occurred in any of the patients. Only 3 patients (9.7%) developed minor postoperative complications (infected socket, dry socket) which were reversible and of short duration). Less than 7% of patients requiring surgical extraction of impacted third molars in our institution were 40 years and above. In addition, minor postoperative complications were seen in only 3 patients. Our result does not support prophylactic surgical extraction of third molars based on the assumption that surgical morbidity increases with age. PMID- 17722818 TI - Aorto-femoral bypass in the HIV infected patient. AB - We describe a 49-year old male Nigerian with HIV infection who presented in our institution with aorto-iliac arterial occlusive disease and progressive severe ischaemic changes of the lower extremity. His preoperative CD4 count was 43 cells / microlitre. He underwent a successful intra-peritoneal aorto-femoral bypass. This report illustrates that vascular reconstruction in an HIV infected patient can be successfully performed with minimal morbidity despite a high risk factor for major infection. The histological finding was in keeping with an accelerated atherosclerosis resulting from HIV infection. PMID- 17722819 TI - Malignant schwannoma of the nasal cavity and paranasal sinuses in a Nigerian. AB - An unusual case of malignant schwannoma with involvement of the forehead, external nose, right nasal cavity, paranasal sinus system (bilateral frontal sinus, right ethmoidal sinus), right orbit and anterior cranial fossa is reported in a Nigerian. Malignant schwannomas of the paranasal sinus are extremely rare, as only 20 well-documented cases have been previously published in English literature. No report in black Africans has been found in extant literature. The clinical features of this tumour are presented with detailed management. The patient had a wide surgical resection of the lesion with reconstruction of the resultant fronto-nasal defect using forehead musculofascial flap plus full thickness skin graft and adjuvant radiotherapy with satisfactory outcome. The good result of combined surgery and radiation regimens in this case demonstrates the usefulness of adjuvant radiation therapy in this condition. PMID- 17722821 TI - [Acupuncture for treatment of kinetic insufficiency of kidney-qi and study on the mechanism]. AB - OBJECTIVE: To observe the therapeutic effect of acupuncture on kinetic insufficiency of kidney-qi and to study on the mechanism. METHODS: Forty-four healthy professional sportsmen were randomly divided into an acupuncture group and a control group. They trained for 4 weeksq with regular detection. In the latter 2 weeks, the acupuncture group received scalp and body-acupuncture. RESULTS: Three weeks later, signs of insufficiency of kidney-qi appeared in most of the sportsmen in the two groups. Two weeks after treatment, in the acupuncture group the signs improved, and testosterone (T) and estradiol (E2) levels increased (P < 0.05); the symptoms did not significantly improve and the T and EZ levels decreased in the control group (P < 0.05). CONCLUSION: Acupuncture therapy can regulate excitatory and inhibitory functions of the nervous system, improve symptoms of kinetic insufficiency of kidney-qi, and has regulative and repairing action on the sexual glands and adrenal gland. PMID- 17722820 TI - [Multi-central randomized controlled trials of electroacupunture at Zhigou (TE 6) for treatment of constipation induced by stagnation or deficiency of qi]. AB - OBJECTIVE: To assess the therapeutic effect and safety of electroacupuncture (EA) at Zhigou (TE 6) on constipation induced by stagnation or deficiency of qi. METHODS: Multi-central randomized controlled trials were adopted and the patients conforming to the criteria for diagnosis, enrolling and excluding were divided into an observation group and a control group according to random number table. The observation group were treated with EA at Zhigou (TE 6) and the control group with EA at non-acupoint for 4 weeks. The cumulative score of clinical symptoms, colon transmission test and various safety indexes were assessed. The following up was carried out 1 and 3 months after the end of treatment. RESULTS: EA at Zhigou (TE 6) could obviously improve clinical symptoms and colon transmission time, decrease using rate of Kaisailu and cathartics, with an effective rate of 94.4%, which was better than 61.3% in the control group (P < 0.0001). CONCLUSION: EA at Zhigou (TE 6) has a function of regulating qi and relaxing the bowels and it is an effective method for treatment of constipation with safety and no adverse effect. PMID- 17722822 TI - [Clinical study on acupuncture, moxibustion, acupuncture plus moxibustion at Weiwanxiashu (EX-B3) for treatment of diabetes]. AB - OBJECTIVE: To compare clinical therapeutic effects of acupuncture, moxibustion, acupuncture plus moxibustion at Weiwanxiashu (EX-B 3) on diabetes. METHODS: Seventy-nine cases of type 2 diabetes were randomly divided into 3 groups: acupuncture group (A), moxibustion group (B) and acupuncture plus moxibustion group (C) and Weiwanxiashu (EX-B 3) was selected in the 3 groups. The main clinical symptoms, fasting blood glucose, 24 hurinal glucose, glycosylated hemoglobin, and blood lipids were investigated and compared before and after treatment. RESULTS: After treatment, the clinical symptoms significantly improved; fasting blood glucose, 24 h-urinal glucose, glycosylated hemoglobin, and cholesterol, triglyceride, low density lipoprotein all decreased in varying degrees, and the high density lipoprotein increased (P < 0.05) in all of the 3 groups, with the effects being the best in the acupuncture plus moxibustion group. CONCLUSION: Acupuncture, moxibustion, or acupuncture plus moxibustion at Weiwanxiashu (EX-B 3) is an effective therapy for diabetes, and the acupuncture plus moxibustion has a better result. PMID- 17722823 TI - [Study on acupuncture treatment of diabetic neurogenic bladder]. AB - OBJECTIVE: To probe into a better therapy for diabetic neurogenic bladder. METHODS: The patients were randomly divided into a treatment group and a control group, 35 cases in each group. The control group were treated with intramuscular injection of Methycobal 250 microg, once every other day; the treatment group were treated with intramuscular injection of Methycobal 250 microg, once every other day, and acupuncture at Guanyuan (CV 4), Shenshu (BL 23), Ciliao (BL 32), Huiyang (BL 35), once every day. The residual urine were compared before and after treatment in the two groups; the effective rate for improvement of symptoms were compared between the two groups. The mental and healthy nursing were conducted for the patients. RESULTS: After treatment, the improving rate for the urgency of urination, frequency of micturition, dribbling urination, urinary incontinence and dysuria in the treatment group was significantly better than that in the control group, but with no significant difference between the two groups in prolongation of urination time. After treatment, the residual urine in the bladder significantly improved in the two groups with more significantly improved in the treatment group than in the control group. CONCLUSION: Methycobal plus acupuncture has a better result than the simple Methyeobal for treatment of diabetic neurogenic bladder, and strengthening nursing care in the treatment can significantly enhance life quality of the patient. PMID- 17722824 TI - [Clinical observation on acupuncture for treatment of diabetic nephropathy]. AB - OBJECTIVE: To observe the clinical therapeutic effect of acupuncture on early metaphase diabetic nephropathy. METHODS: Fifty-four cases of diabetes were randomly divided into an acupuncture group (n=30) and a control group (n=24). The patients in the two groups were all treated by oral administration of Gliguidon or subcutaneous injection of insulin with acupuncture at Ganshu (BL 18), Weiwanxiashu (EX-B 3), Shenshu (BL 23), Guanyuan (CV 4) and other acupoints added in the acupuncture group, for 30 days. RESULTS: The total effective rate was 93.3% in the acupuncture group and 66.7% in the control group. After treatment, blood beta2-microglobulin (beta2-MG), and urine beta2-MG in the acupuncture group decreased significantly with a significant difference as compared with those in the control group; total cholesterol (TC) and triglyceride (TG) significantly decreased and high density lipoprotein (HDL) significantly increased in the acupuncture group with significant differences compared with the control group. CONCLUSION: Acupuncture can improve lipid metabolism and protect the renal function of the patient with early metaphase diabetes. PMID- 17722825 TI - [Clinical observation on penetration needling combined with electroacupuncture for treatment of post-stroke shoulder-hand syndrome]. AB - OBJECTIVE: To probe a method for increasing clinical therapeutic effect of poststroke shoulder-hand syndrome. METHODS: Eighty cases of poststroke shoulder hand syndrome were randomly divided into a treatment group and a control group, 40 cases in each group. The treatment group were treated by penetration needling combined with electroacupuncture, and the control group with routine acupuncture combined with electroacupuncture, once daily, 5 sessions each week, for 4 weeks. Changes of clinical symptoms, articular mobility and pain score were observed. RESULTS: The therapeutic effect in the treatment group was significantly better than that in the control group (P < 0.05). CONCLUSION: Penetration needling combined with electroacupuncture, or routine acupuncture combined with electroacupuncture can effectively alleviate pain, improve motion function and reduce edema, but the penetration needling is better than the routine acupuncture for treatment of poststroke shoulder-hand syndrome. PMID- 17722826 TI - [Observation on therapeutic effect of acupuncture on early peripheral facial paralysis]. AB - OBJECTIVE: To observe therapeutic effects of acupuncture at different opportunities on peripheral facial paralysis. METHODS: Fifty-two cases were randomly divided into a treatment group (n=28) and a control group (n=24). The treatment group at the acute stage (1-10 days) were treated with acupuncture at Dicang (ST 4), Jiache (ST 6), Yangbai (GB 14), etc., with less than 4 points selected on the face and with shallow puncture, and 10 days later electroacupuncture were added at acupoints selected routinely; the control group were treated with the same methods as the treatment group but acupuncture was not given at the acute stage. RESULTS: The cured rate of 78.6% in the treatment group was significantly higher than 50.0% in the control group (P < 0.05). CONCLUSION: Early acupuncture is a key for achieving the best therapeutic effect on facial paralysis. PMID- 17722827 TI - [Clinical observation on selection of acupoints on the same nerve segment for treatment of prolapxe of lumber intervertebral disc]. AB - OBJECTIVE: To search for an effective therapy for prolapse of lumber intervertebral disc. METHODS: One hundred and sixteen cases of such disease were randomly divided into a treatment group (n=66) and a control group (n=50). They were treated respectively with needling acupoints at the same nervous segment and acupoints selected routinely. The clinical therapeutic effects after 2 and 3 courses were observed. RESULTS: The cured and markedly effective rate of 2 courses and the cured rate of 3 courses were 90.9% and 74.2% in the treatment group, respectively, which were better than 66.0% and 32.0% in the control group (P < 0.01). CONCLUSION: The acupoint selection of the same nervous segment is an effective therapy for prolapse of lumber intervertebral disc. PMID- 17722828 TI - [Clinical observation on catgut implantation at acupoint for treatment of somatic form disorders]. AB - OBJECTIVE: To compare therapeutic effects of catgut implantation at acupoint plus small dose of Paroxetine Hydrochloride and simple Paroxetine Hydrochloride. METHODS: Eighty-eight cases of such disease were divided into 2 groups, a treatment group (n=54) and a control group (n=34). The treatment group were treated with catgut implantation at main points Dazhui (GV 14), Zhongwan (CV 12), Tianshu (ST 25), Ganshu (BL 18), Pishu (BL 20), Shenshu (BL 23), etc., plus oral administration of small dose of Paroxetine Hydrochloride; and the control group were treated with simple Paroxetine Hydrochloride. They were treated for 6 weeks. Hamilton Depression Rating Scale (HAMD) was used for assessment of the therapeutic effect. RESULTS: The effective rate was 92.6% in the treatment group and 85.3% in the control group with a significant difference between the two groups (P < 0.05); at the end of the first week and the second week of treatment, the score for HAMD in the treatment group significantly decreased as compared with that in the control group (P < 0.01). CONCLUSION: Catgut implantation at acupoint plus small dose of Paroxetine Hydrochloride has a better therapeutic effect on somatic form disorders. PMID- 17722829 TI - [Effect of acupuncture on rehabilitation training of child's autism]. AB - OBJECTIVE: To observe the effect of acupuncture on rehabilitation training for children's autism. METHODS: Forty autistic children receiving rehabilitation training were divided into a control group and a treatment group, 20 cases in each group. The control group received rehabilitation training including ABA training, the Conductive Education Approach and the training of sensory integration, about 90 sessions for each training; the treatment group received acupuncture treatment for 60-90 sessions after the rehabilitation training. Their results were detected by the revised Chinese version of Psycho-Educational Profile for autistic and developmentally disabled children (C-PEP). RESULTS: The markedly effective rate was 55.0% in the treatment group and 15.0% in the control group with a very significant difference between the two groups (P < 0.01); the differences before and after training in some projects such as the total score of development, imitation, oral cognition in the treatment group were very significantly different from those in the control group (P < 0.01). CONCLUSION: Acupuncture combined with scientific and effective rehabilitation training has a better therapeutic effect than that of the simple rehabilitation training for child's autism. PMID- 17722830 TI - [Clinical observation on acupuncture plus cake-separated moxibustion for treatment of chronic laryngitis]. AB - OBJECTIVE: To search for an effective therapy for chronic laryngitis. Methods Ninety cases of chronic laryngitis were randomly divided into a treatment group of 60 cases and a control group of 30 cases. The treatment group were treated by acupuncture at Futu (LI 18), Renying (ST 9), Shuitu (ST 10), etc. , and cake separated moxibustion at Yongquan (KI 1); the control group with oral administration of Huang's Xiang Sheng Pills. Their therapeutic effects were observed after treatment of 4 weeks. The relationship of syndrome types, pathological types and therapeutic effects with the therapeutic courses in the two groups were compar treatment of chronic . RESULTS: The total effective rate was 96.7 in the treatment group and 76.6% in the control group with a very significant difference between the two groups (P < 0.01); the therapeutic effects for the yin-deficiency and lung-dryness type and the phlegm-heat accumulation type were superior to that of the control group (P < 0.05), and the therapeutic effect for the lung and spleen qi-deficiency type was similar to the control group. The therapeutic effect for chronic simple laryngitis was significantly better than that of the control group (P < 0.05); the therapeutic effect of hypertrophic laryngitis and atrophic laryngitis was similar to that of the control group. CONCLUSION: Acupuncture combined with cake-separated moxibustion has an obvious therapeutic effect on chronic laryngitis. PMID- 17722831 TI - [Observation on therapeutic effect of fire needle therapy on facial spasm]. AB - OBJECTIVE: To compare therapeutic effects of fire needle therapy and filiform needle therapy on facial spasm. METHODS: One hundred and twenty-seven cases of such disease were divided into two groups. The treatment group (n=79) were treated with fire needle therapy at Taiyang (EX-HN 5), Cuanzhu (BL 2) and Quanliao (SI 18), and the control group (n=48) with filiform needle therapy at the same acupoints as those in the treatment group. Their therapeutic effects were compared. RESULTS: The cured rate and the effective rate were 64.6% and 92.4% in the treatment group, and 45.8% and 87.5% in the control group, respectively, with a significant difference between the two groups (P < 0.05). CONCLUSION: Fire needle therapy is an effective therapy for facial spasm, with a therapeutic effect better than that of filiform needle therapy. PMID- 17722832 TI - [Observation on the therapeutic effect of painless festering moxibustion on knee osteoarthritis]. AB - OBJECTIVE: To observe the therapeutic effect of painless festering moxibustion on knee osteoarthritis and to probe into a new therapy. METHODS: Thirty-four cases of knee osteoarthritis were treated with painless festering moxibustion at the best moxibustion part close to the knee joint. The internationally acknowledged knee joint function rating scale (percentage method) including such indexes as pain, walking, joint flexion mobility, instability, engorgement, stair activity and twist-locking before and after treatment was used for assessment of the therapeutic effect. RESULTS: Ten cases were cured, 14 cases were markedly effective, 9 cases were effective and 1 cases was ineffective, with a total effective rate of 97.060%. CONCLUSION: Painless festering moxibustion has an obvious therapeutic effect on knee osteoarthritis. PMID- 17722833 TI - [Summarization of professor He Pu-ren's channel syndrome differentiation for treatment of complicated and difficult diseases]. AB - Channel syndrome differentiation is a more commonly-used syndrome differentiation method of Professor HE Pu-ren clinically, which includes the 3 aspects: differentiation of diseases and syndromes on the channel parts along the body surface; differentiation of diseases and syndromes of the internal organs connected with the channels; differentiation of qi and blood of the channels. According to results of the channel syndrome differentiation, with flexible application of the HE's Santong methods and selection of corresponding treatment program, many complicated and difficult diseases are cured. PMID- 17722834 TI - [Effect of acupuncture serum on the number of osteclast cultured in vitro]. AB - OBJECTIVE: To observe effects of acupuncture serum of ovariectomized rats on the number of in vitro cultural osteoclast of newborn rats. METHODS: Forty 12-month old SD female rats were randomly divided into 4 groups: sham-operation control group, ovariectomized (model) group, acupuncture prevention group and acupuncture treatment group. Osteoclasts isolated from long bone of the newborn SD rat were cultured on 24-well culture plates with DMEM containing 10% the test serum. Forty eight hours later, the osteoclasts were stained with tartrate resistant acid phosphatase (TRAP) and the number of TRAP-positive multinucleated cells were counted. RESULTS: The number of TRAP-positive multinucleated cells in the model group significantly increased as compared with the sham-operation control group (P < 0.01), and in the acupuncture prevention group and the acupuncture treatment group significantly declined compared with the model group (P < 0.05). CONCLUSION: Acupuncture serum can equally reduce the number of osteoclasts in the two group. PMID- 17722835 TI - [Effects of acupuncture on serum insulin antibody and tumor necrosis factor alpha in the experimental rat with insulin resistance]. AB - OBJECTIVE: To observe effects of acupuncture and diet on insulin resistance (IR) and to probe the mechanism. METHODS: Forty SID rats were equally divided into 5 groups: blank group (group I), model group I (group II), model group II (group III), acupuncture group I (group IV) and acupuncture group II (group V). The groups II, III, N and V were fed with high-fat-sugar-salt forage to made IR model, then the groups I, III and V were fed with normal forage, and the groups II and IV with the high-fat-sugar-salt forage, and the acupuncture groups IV and V received acupuncture treatment. Two weeks later, the fasting blood glucose (FBG), plasma insulin (INS), insulin sensitivity index (ISI), INS antibody and tumor necrosis factor alpha (TNF-alpha) were detected. RESULTS: As compared with group I, FBG and INS increased, ISI decreased in the group II (all P < 0.01); as compared with the group II , FBG and INS decreased (all P < 0.01) and ISI increased (P < 0.05, P < 0.01) in the group [II, IV, V; no case with INS antibody (+) in all groups; TNF-alpha in the group II increased compared with that of the group I (P < 0.01), and TNF-alpha in the group III, IV, V decreased compared with that of group II (P < 0.01). CONCLUSION: Acupuncture exerts a reversal effect on insulin resistance, and diet can promotes this effect. The mechanism is carried out possibly through decreasing the secretion of TNF-alpha. PMID- 17722836 TI - [Discussion on randomized controlled trials about clinical researches of acupuncture and moxibustion medicine]. AB - The characteristics of clinical tests of acupuncture and moxibustion were analyzed by studies of the literature about clinical evidence-based trials of acupuncture and moxibustion medicine at present and on the basis of full analysis on the cause of insufficient evidence of clinical researches of acupuncture and moxibustion, in combination with the authors' experiences of clinical studies, and it is put forward that future clinical researches of acupuncture and moxibustion medicine should actively search for new research methods, insist evidence-based acupuncture and moxibustion medical researches, pay attention to retaining own researching characteristics of the acupuncture and moxibustion medicine, accumulate experiences, gradually establish and perfect the assessment system conforming with clinical research methods of acupuncture and moxibustion medicine, elevate the position of acupuncture and moxibustion medicine and develop the acupuncture and moxibustion medicine. PMID- 17722837 TI - [Study on acupuncture and moxibustion for treatment of spinal cord injury at the rehabilitation stage]. AB - OBJECTIVE: To explore the mechanism and methods of acupuncture for the patient of spinal cord injury at the stage of rehabilitation. METHODS: Expound the mechanism of acupuncture for treatment of spinal cord injury and put forward some personal opinions about acupuncture treatment methods according to clinical practice of many years. CONCLUSION: Acupuncture treatment can improve the motor function at the stage of rehabilitation in the patient of spinal cord injury. PMID- 17722838 TI - [Systematic assessment of acupuncture for treatment of herpes zoster in domestic clinical studies]. AB - OBJECTIVE: To assess the effectiveness of acupuncture for treatment of herpes zoster. METHODS: According to the requirement of evidence-based medicine, acupuncture, body acupuncture, electroacupuncture, head acupuncture, three edged needle, plum-blossom needle, fire needle, elongated needle, encircling needling, herpes zoster, etc. were selected as subject words to retrieve the relative medical database at home, and clinically randomized controlled trials were used as enrolled criteria, the treatment group were treated with acupuncture or acupuncture plus other therapies, and the control group with medicine, the cured rate and the time of killing pain for herpes zoster were used as assessment indexes. Altogether 43 papers were enrolled. Among them 10 papers were conducted for Meta-analysis by RevMan 4.2.9. RESULTS: The total OR was 4.27 with 95% CI [2.90, 6.29] of the clinically cured rate in the 10 studies, and the total OR was -7.64 with 95% CI [-8.12, -7.15] of the time of killing pain in the 4 studies. The therapeutic effect in the treatment group on herpes zoster was superior to that of the western medicine (P < 0.01). CONCLUSION: Acupuncture therapy for herpes zoster is effective, but more high-quality studies are required to prove this view point. PMID- 17722839 TI - [Fan Yu-qi and "Taiyi miraculous moxa roll"]. AB - OBJECTIVE: To explore the manipulation method, the range of indications and the characteristics of acupoint selection for "Taiyi miraculous moxa roll". METHODS: Apply computer to make retrieval and statistics of the literature, and then induction and analysis were made by manual methods. CONCLUSION: The "Taiyi miraculous moxa roll" method substitutes moxibustion for acupuncture, with very wide ranges of indications, the most being the thoracico-abdominal diseases, the next being the diseases in the head, and the less being in the limbs and in the lumbodorsal position; so far as the syndrome differentiation is concerned, the most is deficiency syndrome, the next is cold syndrome, wind syndrome, heat syndrome, phlegm syndrome and so on. The most acupoints selected are on the trunk, and the next on the limbs, and then on the head. This method is worth to be popularized. PMID- 17722840 TI - [Zheng Yu-lin, a founder of the acupuncture and moxibustion cause of new China]. AB - Mr. ZHENG Yu-lin is one of the most outstanding acupuncture scientists in the modern times in our country. He inherits the learning handed down in a family and is bold in making innovations, successfully combines the exercises to benefit the internal organs with Chinese traditional acupuncture needling methods, forming a set of unique Zheng's needling methods, which is used for treatment of severe ophthalmopathy with excellent therapeutic effects, and is famed the world over. Main achievements: took on scientific researches of acupuncture and moxibustion, teaching and clinical works in the first stage of establishment of China Academy of Traditional Chinese Medicinel trains a large number of famous specificities of acupuncture and moxibustion for new China; advocates study on channel essence; cures stubborn diseases for leaders of friend countries undertaking the great trust of the central leaders for many times, becoming an important ties of Chinese political foreign affairs. PMID- 17722842 TI - [Homage to McKusick's "Mendelian inheritance in man"]. AB - McKusick's database MIM has grown since its early beginning in sixties to 1985 when the online version (OMIM) appeared. The last edition of three volumes was printed in 1998. It has become a very valuable tool for all geneticists, and also clinicians of other disciplines started using it as a source of important information. The original limitation to disorders with mendelian inheritance has been step by step broken down, all components of human genome and also genes without known function and their epigenetic changes have been included. It was a pleasure for all of us to congratulate to McKusick's honorary degree obtained this year by the oldest European university in Bologna (with a short biography). PMID- 17722841 TI - [Survey of studies on correlation between Helicobacter pylori and cerebral infarction]. AB - OBJECTIVE: To probe into the correlativity of Helicobacter pylori (HP) with cerebral infarction and the possible mechanism. METHODS: Comprehensively discuss the data of studies on the clinical correlativity of HP with cerebral infarction and the possible pathogenic mechanisms. CONCLUSION: Most scholars hold that HP infection is one of risk factors of cerebral infarction. At present, the theory about positive correlation tendency between HP infection and occurrence of cerebral infarction has not been defined. For the mechanism about HP infection possibly inducing cerebral infarction, studies indicate that HP is involved in attack of cerebral infarction possibly alone or via influencing other risk factors, and the pathogenic mechanism mainly include inflammation, immunology and metabolism and so on. However, whether HP infection is a risk factor for attack of cerebral infarction, and the accurate pathogenic mechanisms need further be studied scientifically. PMID- 17722843 TI - [Milestones of cardiovascular therapy. IV. Reserpine]. AB - Reserpine, the purified alkaloid of Rauwolfia serpentina, was the first potent drug widely used in the long-term treatment of hypertension. Rauwolfia serpentina is a tropical woody plant of the Apocyanaceae family ingenious to Asia, South America and Africa. Extracts of its different parts and of plants resembling to rauwolfia were used in Hindu medicine for snakebite, insomnia, insanity and many other diseases and complaints. In Europe, Georg Eberhard Rumpf first reported about rauwolfia in his Herbarium amboinense, 1755. The first modern paper about therapeutic applications of the whole root of rauwolfia was published in 1931 in the Indian Medical Journal by Sen and Bose, and many papers dealing with botanics, chemistry and pharmacology then appeared in Indian and European periodics. In 1949, Vakil published the first report of the antihypertensive effect of rauwolfia in the British Heart Journal. In the Ciba laboratories in Basel, Switzerland, Mueller, Schlittler and Bein analysed various rauwolfia alkaloids and published in 1952 the first complete report about their chemistry and pharmacology. In the same year, reserpine was introduced under the name Serpasil in the treatment of hypertension, tachycardia and thyreotoxicosis. The combination of reserpine, dihydroergocristine and a diuretic is still on the market (Brinerdin, Crystepin). In psychiatry, reserpine was prescribed as a tranqulizing agent until modem synthetic antidepressant and antipsychotic drugs were introduced. The author also briefly summarizes the chemistry, pharmacology and clinical use of reserpine. PMID- 17722844 TI - [Ten years since the successful introduction of the first monoclonal antibody (rituximab) into the therapy of lymphomas]. AB - Cancer treatment is based on combination of systemic chemotherapy and radiotherapy. The new methods of therapy based on biological priniciples have been introduced within last decade. The monoclonal antibody rituximab was launched ten years ago in 1997. This antibody against CD20 antigen, which is expressed on B cell lymphocytes and on the majority of B-cell lymphoid malignancies, has revolutionized the lymphoma therapeutic strategy. The immuno chemotherapy has dramatically improved the outcome of diffuse large B-cell lymphomas patients. The combination of rituximab and chemotherapy as first line therapy has for the first time improved the survival of follicular lymphoma patients previously considered to be incurable. Rituximab has become the inevitable part of therapeutic regimens for other B-cell lymphomas, chronic lymphocytic leukaemia as well as for some non-malignant diseases. The important milestones, the therapeutic results of rituximab and other approved monoclonal antibodies (alemtuzumab, ibritumomab tiuxetan 90Y) is reviewed in this paper as well as short compendium of new antibodies is given. The cost effectiveness of the new therapy is discussed. PMID- 17722845 TI - [Proteomics techniques and their application in haemato-oncologic malignancies]. AB - The understanding haematological malignancies at the protein level is important for the prediction of therapy response, the possibility for disease diagnostics, the development of targeted treatment, and it must be based on the knowledge regarding the molecular pathogenesis of the tumour. 'Proteomics' describes the analysis of the entire proteome of a cell or a tissue and incorporates multiple technologies, including - Western blotting, two-dimensional polyacrylamide gel electrophoresis, mass spectrometry, and ProteinChip-based technology. Although there is a limited number of studies to date in haematological malignancies, those performed highlight the potential impact of these technologies in the discovery of novel markers associated with the drug resistance and the identification of biomarkers which may facilitate the development of a rapid diagnostic test that would be easily applicable in the clinical setting. Thereby this article describes used proteomics techniques and highlights studies regarding proteomic research in haematological malignancies, namely the primarily publications concerning research of multiple myeloma, leukaemias and lymphomas. PMID- 17722846 TI - [Use of capillary electrophoresis in the clinical research]. AB - Capillary electrophoresis (CE) is a modern separation method, which represents a competent alternative to liquid chromatography. The CE separation is performed in very thin silica capillaries. Advantages of CE are the high separation efficiency, low sample consumption and short time of analysis compared to liquid chromatography. CE represents a strong tool for analysis of body fluids. PMID- 17722847 TI - [Thrombotic complications of sepsis and their pharmacological prophylaxis]. AB - Patients with severe sepsis are at increased risk for developing thrombembolic phenomena. This article aims to clarify the association between systemic inflammation activation and coagulation, pathogenesis of coagulation abnormalities during severe sepsis. The article reviews incidence and deep venous thrombosis risk factors among these patients and summarizes recent evidence-based guidelines for deep venous thrombosis prophylaxis. PMID- 17722848 TI - [The information value of detection of borrelia antibodies in the healthy blood donors and in the population at risk]. AB - BACKGROUND: Geographic differences of particular species of ticks and variant strains of Borrelias impede the comparison of local and foreign experience. The authors tried to support some literary observations with their own results and designed a study aimed at determination of anti-Borrelia antibodies (AB) in the selected population samples. The goal of the study was to find and statistically evaluate: a) difference in distribution of values of AB in the sample of probands from the risk and non-risk environment (foresters in Sumava and Prague blood donors, respectively) by means of ELISA method, b) tick bite frequency in the risk and non-risk groups, c) to determine and statistically evaluate the prevalence of probands with increased levels of antiborrelial antibodies in the local study population by ELISA method and the prevalence of probands with non normal values found by Western blot (WB) method. METHODS AND RESULTS: In the group of Prague blood donors (control group), in total 200 probands were examined; in the risk group, 71 probands from Sumava forest were examined. Blood specimens were examined in the National Reference Laboratory for Lyme Borreliosis in Prague. In all specimens, ELISA NRLB KC90 was used. Western blot assay was used for confirmation. CONCLUSIONS: On the basis of literature review from Europe and USA, it is possible to generalize the following, despite some equivocations: 1. regional differences are not significant, with the exception of high-risk territories or "occupational exposure"; 2. there is no significant difference between males and females; 3. considerable caution is necessary in comparing the control and risk groups; prerequisite for such comparison is defining the characteristics of both groups. PMID- 17722849 TI - [Comparison of the activities of the elderly in homes of seniors in 1989 and 2000]. AB - BACKGROUND: One of important factors affecting the life of the residents in seniors' homes (SHs) is their activity in leisure time. The objective of our work was to describe these activities and their development in a period of eleven years. METHODS AND RESULTS: We have examined two sets of inhabitants of SHs with our own standardized interview: all 48 residents of one SH (average age 69.3 years) in 1989, and randomly selected 59 residents of four SHs (average age 71.2 years) in 2000. In our questionnaire, seniors answered if they took part in some of the proposed activities. The two sets of inhabitants were compared with each other, in sex and age groups, and according to cognitive impairments and mobility. In statistical evaluations we used the chi-square test in contingency tables. The inhabitants reported 179 activities, on average 3.7 activities per one resident in 1989. In 2000 they presented 187 activities, and the average (3.2 activities per one resident) decreased slightly. In both years, the most frequent activities were walking outdoors, watching TV and listening to radio. In six of the compared activities we observed a decrease in the number of residents pursuing them in 2000. When comparing the activities in sexes, we observed a greater decrease in activities in women than in men. Comparisons in age groups revealed a greater decrease of activities in "old" inhabitants (75 + years). In 2000, a considerable number of residents (without regard to age) took part in activities organized by institutions. We observed a significant increase in the number of residents with cognitive impairments and mobility deficits. CONCLUSIONS: The authors point at the issue of leisure time activities of the elderly in seniors' homes. In the monitored period of eleven years, a decrease of activities was observed. PMID- 17722850 TI - [Clostridial sepsis and gas gangrene of the abdominal wall after cholecystectomy]. AB - Clostridial sepsis is a rare complication after intraabdominal operations, mostly fatal. According to our knowledge only two papers describing clostridial sepsis as postoperative complication in 4 patients were published in the Czech literature, only one of them survived. Authors present a case report of patient operated on for cholecystolithiasis and obstructive icterus where within 48 hours after cholecystectomy the clostridial sepsis and gas gangrene of the abdominal wall developed and that were successfuly managed. PMID- 17722851 TI - EPO crisis: are we turning a corner? PMID- 17722852 TI - Dialysis and PKD patients: an analysis. PMID- 17722853 TI - Hemoglobin levels, quality of life, and survival. PMID- 17722855 TI - Even for a minimalist, EPO has clear value. PMID- 17722854 TI - Dialysis without [adequate] EPO. PMID- 17722856 TI - EPO use: let the patients be involved in the decision. PMID- 17722857 TI - Making a difference. PMID- 17722858 TI - Why I raise money for kidney disease research. PMID- 17722859 TI - My experiences. From sound stage to end-stage... Tinseltown learns about kidney failure. PMID- 17722860 TI - Upcoming and future strategies of tick control: a review. AB - Ticks are distributed worldwide and significantly impact human and animal health. Due to severe problems associated with the continuous use of acaricides on animals, integrated tick management is recommended. Increasing public health concern over the tick-borne diseases demands the strategic control of ticks on animals that transmit diseases to human beings. Immunological control of tick vector of Kyasanur Forest Disease (KFD) on cattle and other wild reservoir hosts is one of the possible alternative strategy for reducing the transmission of KFD to man. Chemical-vaccine synergies have been demonstrated and a combination of chemical and vaccine for tick and tick-borne disease control has been identified as a sustainable option. Studies have suggested the possibility of vaccine strategies directed towards both tick control and transmission of pathogens. Besides tick vaccine, use of endosymbionts, which are essential for the survival of arthropod hosts, for the control of tick vectors will be one of the targeted areas of research in near future. India with huge natural resources of herbs and other medicinal plants, the possibilities of developing herbal acaricides is discussed. The future of research directed towards target identification is exciting because of new and emerging technologies for gene discovery and vaccine formulation. PMID- 17722861 TI - The distribution of interstitial cells of Cajal in the ileum is not altered by infection with Schistosoma mansoni. AB - BACKGROUND & OBJECTIVES: The interstitial cells of Cajal (ICC) act as pacemakers that generate slow waves and function as a relay between smooth muscle cells of the gastrointestinal (GI) tract. Recent reports indicate the crucial role played by the ICC in defining GI motility during human disease status like pyloric stenosis, Hirschsprung's disease and ulcerative colitis. Experimental data showed that Nippostrongylus infection in the rat caused an altered GI motility pattern accompanied by a complete loss of ICC-deep muscular plexus. The aim of the present study was to delineate if ICC were similarly affected during Schistosoma mansoni infections, thereby responsible for the disturbed GI motility patterns triggered in the afflicted mammalian host. METHODS & RESULTS: Immunohistochemistry was done using whole mounts and sections from naive and S. mansoni infected mice ileum. Primary antibodies detected Kit-immunoreactivity (Kit-ir representing ICC), PGP-9.5 (protein gene product 9.5 representing a neuronal marker), SK3 (ionic channel marker for non-Kit fibroblast like cells), and Cx43 (gap junction protein representing a muscle marker). Single/double immunofluorescence staining and confocal microscopy depicted that muscle thickness (Cx43-ir) and inflammatory infiltrate increased with infection. Kit-ir ICC and SK3-ir fibroblast like cells (FLC) were present at all normal locations as seen in controls and during acute and chronic stages of infection. INTERPRETATION & CONCLUSION: No disappearance of either ICC population was noted. A preferential (although not exclusive) location of inflammatory infiltrate in contact with SK3-ir FLC in the muscle layer was observed. The present study thus delineated that ICC are not affected during S. mansoni infections, and thereby may not be responsible for mediating the disturbed GI motility patterns caused by schistosomiasis. PMID- 17722862 TI - Maternal malaria during pregnancy and infant mortality rate: critical literature review and a new analytical approach. AB - BACKGROUND & OBJECTIVES: Malaria during pregnancy is a recognised risk factor for low birth weight and probably decreases the survival of offspring, particularly during their first month of life. On the other hand, acquired maternal immunity may protect infants against malaria infection or disease. This study assesses these two opposite effects simultaneously. METHODS: We used the data of a large epidemiological study on malaria (Garki project) to analyse the impact of malaria during pregnancy on survival of offspring in their first year of life. The dataset contains 138,197 survey records, representing 12,849 subjects. Of 663 reported deliveries, 417 could be linked to survival data for the newborn. RESULTS: The mortality rate during the first year of life was independent of maternal malaria infection during pregnancy (crude rate ratio 1.0). After adjustment for malaria in infancy, the rate ratio was 1.2. The corresponding rate ratios for maternal malaria during the second half of pregnancy were 1.46 and 1.73. None of these rate ratios was statistically significant. This may be due to the small number of deaths in the first year of life with a complete record of maternal malaria (27 deaths). The infants during the first four months of life had the lowest risk for Plasmodium falciparum, R malariae and P. ovale infections which may be partly due to acquired maternal immunity. There was a positive association between malaria during pregnancy and malaria during first year of life which might be due to similarity in exposure risks within a family, or confounding effects of socioeconomic status. However, this association was weaker in the first four months of life, and in those women who contracted infection during the second half of pregnancy. This may indicate that acquired immunity is stronger in this group and partially protects babies for a few months. INTERPRETATION & CONCLUSION: It seems that on the whole, malaria during pregnancy was not a major risk factor for infant mortality in the Garki project. These results suggest that ignoring acquired maternal immunity may overestimate the hazard of malaria during pregnancy on infant survival. PMID- 17722863 TI - Bacterial, fungal and parasitic contamination of cockroaches in public hospitals of Hamadan, Iran. AB - BACKGROUND & OBJECTIVES: To determine the possible role of cockroaches in dissemination of medically important microorganisms, a study was carried out in public hospitals and residential areas of Hamadan city, west of Iran. Bacteria, fungi and parasites of medical importance were isolated and identified. The total number of Blattella germanica collected from hospitals were 133 as the case group. The cockroaches collected from residential areas were 45 as the control group. METHODS: A total of 178 cockroaches were collected, over a period of two years (133 from hospitals; and 45 from residential areas) in Hamadan. Medically important microorganisms were isolated from external and internal surfaces using standard methods. RESULTS: In the case group, 130 out of 133 (98%) Blattella germanica showed contamination with high bacterial load (more than 1 x 10(3)) whereas only 2 out of 45 (4.45%) cockroaches of the control group were carrying medically important bacteria with high bacterial load. Bacteriological examinations revealed that almost all test cockroaches had at least one of the following microorganisms either in their body surface or digestive tract. Enterobacter (22.6%), Klebsiela (21%), Enterococcus (17.3%), Staphylococcus (16.5%), Esherichia coli and Streptococcus (8.3%), Pseudomonas (3%), and also Shigella, Haemophilus and group A beta-hemolytic Streptococcus each less than 1%. In addition the results showed (74.4.%) of test cockroaches harboured fungi Candida (48.9%), Mucor (10.5%), Aspergillus niger (7.5%), Rhizopus (4.5) and also Penicillium and Aspergillus fumigans each 1.5%. Some parasitic worms of medical importance were also isolated from the test cockroaches, but carriage rates were low. INTERPRETATION & CONCLUSION: The data from this study emphasise the importance of cockroaches as potential vectors of medically important microorganisms such as pathogenic bacteria and fungi in hospital environments. PMID- 17722865 TI - Oxidoreductases in early gestational monkey placenta during maternal malarial infection: histochemical localisation. AB - BACKGROUND & OBJECTIVES: Early gestational malaria is more deleterious than late gestational infection. Still the pathophysiology of maternofoetal organ--the placenta in malaria remains almost unexplored during early gestation. Present study dealing with oxidoreductases in early gestational placenta during maternal malarial infection of Plasmodium cynomolgi bastianellii in rhesus monkeys was anticipated to provide a better insight into the functional impairment of this organ leading to foetal abnormalities. METHODS: Three control and four experimental monkeys (Macaca mulatta) were quarantined for one month prior to experimentation. Experimental monkeys at 2- 2 1/2 months of gestation were inoculated with P. cynomolgi bastianellii. On attaining first peak of parasitaemia the placentae were collected from anesthetised animals. The snap frozen, cryostat sections were subjected to histochemical localisation for 3 (or 17) beta-hydroxysteroid dehydrogenase (beta-HSD) [3 (or 17) beta-hydroxysteroid: NAD (P+) oxidoreductase, EC 1.1.1.51 hydroxysteroid dehydrogenases] and NADPH tetrazolium reductase [NADPH: (acceptor) oxidoreductase, EC 1.6.99.1 NADPH-TR]. Comparative microscopy of control and malaria infected placental sections was performed and analysed. RESULTS: A localised decrease in both the enzymes was observed in syncytiotrophoblast layer of malaria infected monkey placenta. The areas showing morphological damage of syncytiotrophoblast were also depicting gross reduction in NADPH-TR activity. INTERPRETATION & CONCLUSION: The altered enzymatic activities [3 (or 17) beta-HSD and NADPH-TR] in malaria infected early gestational monkey placenta have been discussed in the light of placental function. It could be concluded by present studies that these alterations would affect the cellular metabolism especially steroidogenesis and detoxification process which in turn would affect the normal development of the foetus as well as maintenance of gestation. PMID- 17722864 TI - CD4 count, viral load and parasite density of HIV positive individuals undergoing malaria treatment with dihydroartemisinin in Benin City, Edo state, Nigeria. AB - BACKGROUND & OBJECTIVES: A prospective study on 72 HIV infected and 33 HIV negative individuals undergoing malaria treatment with dihydroartemisinin (Cotecxin) was undertaken to compare CD4 cells count, viral load and parasite density at two time-points, a baseline visit and a 9-day post-treatment visit. METHODS: CD4 count and viral load of the subjects were estimated using Dynabeads T4-T8 Quantification Protocol (Dyneal Biotech, Norway) and Amplicor HIV-1 Monitor Test respectively (Roche, United Kingdom). RESULTS: There was a significant decrease in CD4 count at 9-day post-treatment when compared with baseline value (p < 0.05) in HIV infected individuals with CD4 < or =200 cells/microl. Also, the 9-day post-treatment viral load value was statistically higher than the baseline value (p < 0.05). In HIV positive patients with CD4 >200 cells/microl, a marked significant increase was obtained when the mean viral load at baseline was compared to the 9-day post-treatment visit value (p <0.05). The mean parasite density in HIV positive subjects was statistically higher when compared to that of HIV negative individuals at baseline and 9-day post-treatment (p < 0.05). INTERPRETATION & CONCLUSION: The study as such may not confirm the impact of malaria infection on progression to AIDS, incorporating effective malaria control in HIV management programmes may improve tremendously the quality of life of HIV infected individuals. PMID- 17722866 TI - Influence of biological and physicochemical characteristics of larval habitats on the body size of Anopheles gambiae mosquitoes (Diptera: Culicidae) along the Kenyan coast. AB - BACKGROUND & OBJECTIVES: The number and productivity of larval habitats ultimately determine the density of adult mosquitoes. The biological and physicochemical conditions at the larval habitat affect larval development hence affecting the adult body size. The influence of biological and physicochemical characteristics on the body size of Anopheles gambiae was assessed in Jaribuni village, Kilifi district along the Kenyan Coast. METHODS: Ten cages measuring 1 x 1 x 1 m (1 m3) with a netting material were placed in 10 different aquatic habitats, which were positive for anopheline mosquito larvae. Emergent mosquitoes were collected daily by aspiration and the wing lengths were determined by microscopy. In the habitats, physicochemical parameters were assessed: pH, surface debris, algae and emergent plants, turbidity, substrate, nitrate, ammonia, phosphate and chlorophyll a content. RESULTS: A total of 685 anopheline and culicine mosquitoes were collected from the emergent cages. Only female mosquitoes were considered in this study. Among the Anopheles spp, 202 were An. gambiae s.s., eight An. arabiensis, two An. funestus, whereas the Culex spp was composed of 214 Cx. quinquefasciatus, 10 Cx. tigripes, eight Cx. annulioris and one Cx. cumminsii. The mean wing length of the female An. gambiae s.s. mosquitoes was 3.02 mm (n=157), while that of An. arabiensis was 3.09 mm (n=9). There were no associations between the wing lengths and the environmental and chemical parameters, except for a positive correlation between wing length of An. gambiae and chlorophyll a content (r = 0.622). The day on which the mosquitoes emerged was not significant for the anopheline (p = 0.324) or culicine mosquitoes (p = 0.374), because the mosquito emerged from the cages on a daily basis. INTERPRETATION & CONCLUSION: In conclusion, there was variability in production of emergent mosquitoes from different habitats, which means that there should be targeted control on these habitats based on productivity. PMID- 17722867 TI - Alpha 2 macroglobulin activity in rats infected with Typanosoma lewisi and treated with cyclophosphamide and its effect on the malignancy of the disease. AB - BACKGROUND & OBJECTIVES: Trypanosoma lewisi is a common, flagellated parasite of the rat. Our previous study showed that rabbits injected with serum collected from rats infected with Trypanosoma lewisi and treated with cyclophosphamide (CyI) produced high levels of antibodies against a new protein in the CyI rat serum. RESULTS: In the present study, this protein was characterised as alpha2 macroglobulin (alpha2M) and the kinetics of its production and its influence on the malignancy of the disease were determined. In rats infected with T. lewisi, alpha2M was first demonstrated and peaked on the second day post-infection (972 microg/ml) and then reduced gradually, reaching a level of 32 microg/ml on the eighth day post-infection. However, in the CyI rats the level of alpha2M was gradually increased as the disease progressed, reaching a level of 890 microg/ml on the eighth day post-infection. Injection of both crude and purified alpha2M into rats infected with T. lewisi led to increased parasitaemia. INTERPRETATION & CONCLUSION: The present study suggests that increased levels of alpha2M in the CyI rats contribute to the malignancy of the disease. PMID- 17722868 TI - Impact of Olyset nets on malaria transmission in India. AB - BACKGROUND & OBJECTIVES: Efficacy of Olyset nets, long-lasting insecticidal nets were tested from August 2003 to August 2006 against Anopheles culicifacies, the vector which transmits 60% of all malaria cases in rural India. METHODS: Three villages in District Gautam Budh Nagar (Uttar Pradesh), India were selected for the trial and Olyset nets were distributed in one village, in another village untreated nets were distributed and the third village was kept as control where nets were not used. Entomological, and epidemiological data were collected using standard methods. RESULTS: The use of Olyset nets reduced the indoor resting density of An. culicifacies and also reduced mosquito entry into the structures where Olyset nets were used. No mosquitoes were caught landing on the Olyset nets. There was a reduction in the parity rate of An. culicifacies in the Olyset net village as compared with untreated net and no net villages. The impact of Olyset nets was observed on malaria incidence and only one case of Plasmodiumfalciparum malaria was reported in the Olyset net village but these continued to be found in the village with untreated nets and the control. CONCLUSION: Results of the present study confirmed that Olyset nets are highly effective in reducing the indoor resting density of mosquitoes, man-vector contact and malaria incidence. PMID- 17722869 TI - Preliminary evaluation of mosquito larvicidal efficacy of plant extracts. PMID- 17722870 TI - Seasonal prevalence of malaria vectors in Sonitpur district of Assam, India. PMID- 17722871 TI - A note on the serum potassium level among thai hospitalised patients with falciparum malaria. PMID- 17722873 TI - Release of D-xylose from wheat straw by acid and xylanase hydrolysis and purification of xylitol. AB - Xylitol is a valuable sweetener produced from xylose-rich biomass. Our objective was to optimize conditions for maximum release of D-xylose from wheat straw by acid or enzyme hydrolysis with minimal release of other monosaccharides, and to purify xylitol from three other alditols. Ground straw was treated with 10 parts of 0.2-0.4 M sulfuric acid at 110-130 degrees C for 15-45 min or at reflux with 0.75-1.25 M sulfuric acid for 1.5-3 h. Under optimum conditions of either 0.3 M acid at 123 degrees C for 28 min or 1.0 M acid at 100 degrees C for 3 h, 18 or 19% of D-xylose plus approximately 6% other sugars were produced from straw (dry basis). A 16% yield of D-xylose plus 6% other sugars was obtained when hydrothermally (10% straw, 160 degrees C, 1 h) treated straw was incubated with a commercial xylanase. The lack of enzyme specificity for D-xylose release was attributed to the autohydrolysis of polysaccharides during the pretreatment plus slow hydrolysis of cellulose during enzyme digestion. Xylitol with a purity of 95% was obtained in 10% yield from straw after the reduction of an acid hydrolyzate followed by fractional crystallization. Purification of the mixture of four alditols by open-column chromatography on a strongly basic anion-exchange resin in hydroxide form gave 7% xylitol crystals with a purity of 99%. PMID- 17722872 TI - Pomegranate ellagitannin-derived metabolites inhibit prostate cancer growth and localize to the mouse prostate gland. AB - Our group has shown in a phase II clinical trial that pomegranate juice (PJ) increases prostate specific antigen (PSA) doubling time in prostate cancer (CaP) patients with a rising PSA. Ellagitannins (ETs) are the most abundant polyphenols present in PJ and contribute greatly towards its reported biological properties. On consumption, ETs hydrolyze to release ellagic acid (EA), which is then converted by gut microflora to 3,8-dihydroxy-6H-dibenzo[b, d]pyran-6-one (urolithin A, UA) derivatives. Despite the accumulating knowledge of ET metabolism in animals and humans, there is no available data on the pharmacokinetics and tissue disposition of urolithins. Using a standardized ET enriched pomegranate extract (PE), we sought to further define the metabolism and tissue distribution of ET metabolites. PE and UA (synthesized in our laboratory) were administered to C57BL/6 wild-type male mice, and metabolite levels in plasma and tissues were determined over 24 h. ET metabolites were concentrated at higher levels in mouse prostate, colon, and intestinal tissues as compared to other tissues after administration of PE or UA. We also evaluated the effects of PE on CaP growth in severe combined immunodeficient (SCID) mice injected subcutaneously with human CaP cells (LAPC-4). PE significantly inhibited LAPC-4 xenograft growth in SCID mice as compared to vehicle control. Finally, EA and several synthesized urolithins were shown to inhibit the growth of human CaP cells in vitro. The chemopreventive potential of pomegranate ETs and localization of their bioactive metabolites in mouse prostate tissue suggest that pomegranate may play a role in CaP treatment and chemoprevention. This warrants future human tissue bioavailability studies and further clinical studies in men with CaP. PMID- 17722874 TI - Design of HIV protease inhibitors targeting protein backbone: an effective strategy for combating drug resistance. AB - The discovery of human immunodeficiency virus (HIV) protease inhibitors (PIs) and their utilization in highly active antiretroviral therapy (HAART) have been a major turning point in the management of HIV/acquired immune-deficiency syndrome (AIDS). However, despite the successes in disease management and the decrease of HIV/AIDS-related mortality, several drawbacks continue to hamper first-generation protease inhibitor therapies. The rapid emergence of drug resistance has become the most urgent concern because it renders current treatments ineffective and therefore compels the scientific community to continue efforts in the design of inhibitors that can efficiently combat drug resistance. The present line of research focuses on the presumption that an inhibitor that can maximize interactions in the HIV-1 protease active site, particularly with the enzyme backbone atoms, will likely retain these interactions with mutant enzymes. Our structure-based design of HIV PIs specifically targeting the protein backbone has led to exceedingly potent inhibitors with superb resistance profiles. We initially introduced new structural templates, particulary nonpeptidic conformationally constrained P 2 ligands that would efficiently mimic peptide binding in the S 2 subsite of the protease and provide enhanced bioavailability to the inhibitor. Cyclic ether derived ligands appeared as privileged structural features and allowed us to obtain a series of potent PIs. Following our structure based design approach, we developed a high-affinity 3( R),3a( R),6a( R)-bis tetrahydrofuranylurethane (bis-THF) ligand that maximizes hydrogen bonding and hyrophobic interactions in the protease S 2 subsite. Combination of this ligand with a range of different isosteres led to a series of exceedingly potent inhibitors. Darunavir, initially TMC-114, which combines the bis-THF ligand with a sulfonamide isostere, directly resulted from this line of research. This inhibitor displayed unprecedented enzyme inhibitory potency ( K i = 16 pM) and antiviral activity (IC 90 = 4.1 nM). Most importantly, it consistently retained is potency against highly drug-resistant HIV strains. Darunavir's IC 50 remained in the low nanomolar range against highly mutated HIV strains that displayed resistance to most available PIs. Our detailed crystal structure analyses of darunavir-bound protease complexes clearly demonstrated extensive hydrogen bonding between the inhibitor and the protease backbone. Most strikingly, these analyses provided ample evidence of the unique contribution of the bis-THF as a P 2-ligand. With numerous hydrogen bonds, bis-THF was shown to closely and tightly bind to the backbone atoms of the S 2 subsite of the protease. Such tight interactions were consistently observed with mutant proteases and might therefore account for the unusually high resistance profile of darunavir. Optimization attempts of the backbone binding in other subsites of the enzyme, through rational modifications of the isostere or tailor made P 2 ligands, led to equally impressive inhibitors with excellent resistance profiles. The concept of targeting the protein backbone in current structure-based drug design may offer a reliable strategy for combating drug resistance. PMID- 17722875 TI - N-benzyl-2-(6,8-dichloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)-N-(6-(7 nitrobenzo[c][1,2,5]oxadiazol-4-ylamino)hexyl)acetamide as a new fluorescent probe for peripheral benzodiazepine receptor and microglial cell visualization. AB - The aim of this work was to develop new fluorescent probes for the localization and function of the peripheral benzodiazepine receptor (PBR). This receptor is primarily expressed on the mitochondria, and it is overexpressed in a variety of different states including glioma, breast cancer, Alzeheimer's disease, and activated microglia. For the mentioned purpose, imidazopyridine and imidazopyrimidine compounds 5-20 were synthesized, and their affinity for PBR was determined. Although some intrinsically fluorescent imidazopyrimidine compounds 12-20 possess good binding affinity, they cannot be used for visualizing PBR due to their unfavorable fluorescence characteristics. Among the imidazopyridine-7 nitrofurazan conjugates 5-11, compound 10 was the most active, and it was found to stain live Ra2 microglial cells effectively. An in vivo biodistribution study carried out on compound 10 showed that this imidazopyridine derivative, injected in the carotid artery, is able to penetrate to liver parenchyma, whereas fluorescein isothiocyanate labeled dextran (FITC-dextran), used as a control dye, hardly penetrated from blood vessels to tissues. On the other hand, as for the distribution to brain, the patterns of staining with 10 and FITC-dextran are similar, indicating that both of them hardly penetrate into the brain because of the existence of the blood-brain barrier. The obtained results indicate that compound 10 represents a new useful fluorescent probe for visualization of activated microglia and PBR. PMID- 17722876 TI - Design of a thermocontrollable protein complex. AB - It is widely recognized that stimuli-responsive nanostructures play a promising role in nanodevices for medical treatments and experimental tools. We have designed and constructed a basic structure which controls the distance between two termini domains through temperature reversibility. Our structure, shaped like a bouquet, is composed of two proteins, alpha-helix and elastin-like protein (ELP). Alpha-helices align and bundle the ELP while ELP twists and forms a fiber like structure at warm temperatures. This ELP conformational change alters the distance between the structure termini at the site opposite the alpha-helix. We connected enhanced yellow fluorescent protein (EYFP) and enhanced cyan fluorescent protein (ECFP) at the structure's two termini to evaluate the distance using fluorescence resonance energy transfer (FRET) efficiency. These proteins spontaneously formed a complex which decreased the distance between the two fluorescent proteins located at its termini, at physiologically relevant temperatures. This change was repeated with complete reversibility (n = 5). PMID- 17722877 TI - Tandem 3D-QSARs approach as a valuable tool to predict binding affinity data: design of new Gly/NMDA receptor antagonists as a key study. AB - Quantitative structure-activity relationships (QSARs) represent a very well consolidated computational approach to correlate structural or property descriptors of chemical compounds with their chemical or biological activities. We have recently reported that autocorrelation Molecular Electrostatic Potential (autoMEP) vectors in combination to Partial Least-Square (PLS) analysis or to Response Surface Analysis (RSA) can represent an interesting alternative 3D-QSAR strategy. In the present paper, we would like to present how the applicability of in tandem linear and nonlinear 3D-QSAR methods (autoMEP/PLS&RSA) can help to predict binding affinity data of a new set of N-methyl-d-aspartate (Gly/NMDA) receptor antagonists. PMID- 17722880 TI - Gold nanoparticle chemiresistor sensors: direct sensing of organics in aqueous electrolyte solution. AB - A novel chemiresistor sensor for detection of organic analytes in high conductivity aqueous electrolyte solution is reported. The chemiresistor sensor is based on thin films of gold nanoparticles capped with a 1-hexanethiol monolayer that is inkjet printed onto a microelectrode. In order for a change in nanoparticle film resistance to be measured, the electronic conduction must preferentially occur through the nanoparticle film rather than through the high conductivity electrolyte solution. This was achieved by miniaturizing the chemiresistor device such that the double layer capacitance of the electrodes in contact with the electrolyte solution gives rise to a significantly larger impedance compared to the nanoparticle film resistance. This system was shown to be sensitive to simple organics dissolved in an aqueous electrolyte solution. The organic analytes, dissolved in the aqueous solution, partition into the hydrophobic nanoparticle film causing the nanoparticle film to swell, resulting in an increase in the low-frequency impedance of the sensor. An increase in the impedance, at 1 Hz, of the gold nanoparticle chemiresistor on exposure to toluene, dichloromethane, and ethanol dissolved in 1 M KCl solution was demonstrated with detection limits of 0.1, 10, and 3000 ppm, respectively. Titration curves over 3 orders of magnitude could be obtained for analytes such as toluene. PMID- 17722878 TI - Iron(III)-catecholato complexes as structural and functional models of the intradiol-cleaving catechol dioxygenases. AB - The structural and spectroscopic characterization of mononuclear iron(III) catecholato complexes of ligand L4 (methyl bis(1-methylimidazol-2-yl)(2 hydroxyphenyl)methyl ether, HL4) are described, which closely mimic the enzyme substrate complex of the intradiol-cleaving catechol dioxygenases. The tridentate, tripodal monoanionic ligand framework of L4 incorporates one phenolato and two imidazole donor groups and thus well reproduces the His2Tyr endogenous donor set. In fact, regarding the structural features of [FeIII(L4)(tcc)(H2O)] (5.H2O, tcc = tetrachlorocatechol) in the solid state, the complex constitutes the closest structural model reported to date. The iron(III) catecholato complexes mimic both the structural features of the active site and its spectroscopic characteristics. As part of its spectroscopic characterization, the electron paramagnetic resonance (EPR) spectra were successfully simulated using a simple model that accounts for D strain. The simulation procedure showed that the observed g = 4.3 line is an intrinsic part of the EPR envelope of the studied complexes and should not necessarily be attributed to a highly rhombic impurity. [FeIII(L4)(dtbc)(H2O)] (dtbc = 3,5-di-tert-butylcatechol) was studied with respect to its dioxygen reactivity, and oxidative cleavage of the substrate was observed. Intradiol- and extradiol-type cleavage products were found in roughly equal amounts. This shows that an accurate structural model of the first coordination sphere of the active site is not sufficient for obtaining regioselectivity. PMID- 17722879 TI - Branched poly(lactide) synthesized by enzymatic polymerization: effects of molecular branches and stereochemistry on enzymatic degradation and alkaline hydrolysis. AB - In this article the effects of the number of molecular branches (chain ends) and the stereochemistry of poly(lactide)s (PLAs) on the enzymatic degradation and alkaline hydrolysis are studied. Various linear and branched PLAs were synthesized using lipase PS (Pseudomonas fluorescens)-catalyzed ring-opening polymerization (ROP) of lactide monomers having different stereochemistries (L lactide, D-lactide, and D,L-lactide). Five different alcohols were used as initiators for the ROP, and the monomer-to-initiator molar feed ratio was varied from 10 to 100 and 1000 for each branch in the polymer architecture. The properties of branched PLAs that would affect the enzymatic and alkaline degradations, i.e., the glass transition temperature, the melting temperature, the melting enthalpy, and the advancing contact angle, were determined. The PLA films were degraded using proteinase K or 1.0 M NaOH solution, and the weight loss and changes in the number average molecular weight (Mn) of the polymer were studied during 12 h of degradation. The results suggest that an increase in the number of molecular branches of branched PLAs enhances its enzymatic degradability and alkali hydrolyzability. Moreover, the change in Mn of the branched poly(L-lactide) (PLLA) by alkaline hydrolysis indicated that the decrease in Mn was in the first place dependent on the number of molecular branches and thereafter on the length of the molecular branch of branched PLA. The branched PLLA, poly(D-lactide) (PDLA), and poly(D,L-lactide) (PDLLA) differed in weight loss and change in Mn of the PLA segment during the enzymatic degradation. It is suggested that the branched PDLLA was degraded preferentially by proteinase K. PMID- 17722881 TI - Aptamer-based rolling circle amplification: a platform for electrochemical detection of protein. AB - Aptamer-based rolling circle amplification (aptamer-RCA) was developed as a novel versatile electrochemical platform for ultrasensitive detection of protein. This method utilized antibodies immobilized on the electrode surface to capture the protein target, and the surface-captured protein was then sandwiched by an aptamer-primer complex. The aptamer-primer sequence mediated an in situ RCA reaction that generated hundreds of copies of a circular DNA template. Detection of the amplified copies via enzymatic silver deposition then allowed enormous sensitivity enhancement in the assay of target protein. This novel aptamer-primer design circumvented time-consuming preparation of the antibody-DNA conjugate for the common immuno-RCA assay. Moreover, the detection strategy based on enzymatic silver deposition enabled a highly efficient readout of the RCA product as compared to a redox-labeled probe based procedure that might exhibit low detection efficiency due to RCA product distance from the electrode. With the platelet-derived growth factor B-chain (PDGF-BB) as a model target, it was demonstrated that the presented method was highly sensitive and specific with a wide detection range of 4 orders of magnitude and a detection limit as low as 10 fM. Because of the wide availability of aptamers for numerous proteins, this platform holds great promise in ultrasensitive immunoassay. PMID- 17722882 TI - A general, positive ion mode ESI-MS approach for the analysis of singly charged inorganic and organic anions using a dicationic reagent. AB - Anion analysis continues to be of great importance to many scientific and technical fields. We propose here a general and sensitive method of detecting singly charged anions by ESI-MS and LC-ESI-MS as positive ions. This method utilizes a dicationic reagent to form a complex with the anion that retains an overall positive charge for analysis by MS. Nitrate, thiocyanate, perchlorate, perfluorooctanoic acid (PFOA), halogenated acetic acids, and various other inorganic and organic anions and are investigated. The use of tandem mass spectrometry to enhance the detection limits of some of the anions is demonstrated. Chaotropic anions provided the lowest detection limits, with PFOA detected at the hundreds of femtograms level. Indeed, this single approach provides the lowest reported detection limits for a variety of anions, especially PFOA, nitrate, monochloroacetic acid, dichloroacetic acid, and bromochloroacetic acid, among others. The integrated areas and signal-to-noise ratios for five ions during a chromatographic run in both the positive and negative ion modes are compared. The ability of this method to detect differences in related ions is shown for four arsenic species. Finally, a tap water sample is analyzed for the anions in this study using the dicationic reagent method. PMID- 17722883 TI - A C-terminal dimerization motif is required for focal adhesion targeting of Talin1 and the interaction of the Talin1 I/LWEQ module with F-actin. AB - Focal adhesion complexes are plasma membrane-associated multicomponent complexes that are essential for integrin-linked signal transduction as well as cell adhesion and cell motility. The cytoskeletal protein Talin1 links integrin adhesion receptors with the actin cytoskeleton. Talin1 and the other animal and amoebozoan talins are members of the I/LWEQ module superfamily, which also includes fungal Sla2 and animal Hip1/Hip1R. The I/LWEQ module is a conserved C terminal structural element that is critical for I/LWEQ module protein function. The I/LWEQ module of Talin1 binds to F-actin and targets the protein to focal adhesions in vivo. The I/LWEQ modules of Sla2 and Hip1 are required for the participation of these proteins in endocytosis. In addition to these roles in I/LWEQ module protein function, we have recently shown that the I/LWEQ module also contains a determinant for protein dimerization. Taken together, these results suggest that actin binding, subcellular targeting, and dimerization are associated in I/LWEQ module proteins. In this report we have used alanine scanning mutagenesis of a putative coiled coil at the C-terminus of the Talin1 I/LWEQ module to show that the amino acids responsible for dimerization are necessary for F-actin binding, the stabilization of actin filaments, the cross linking of actin filaments, and focal adhesion targeting. Our results suggest that this conserved dimerization motif in the I/LWEQ module plays an essential role in the function of Talin1 as a component of focal adhesions and, by extension, the other I/LWEQ module proteins in other multicomponent assemblies involved in cell adhesion and vesicle trafficking. PMID- 17722884 TI - A fluorescence method to define transmembrane alpha-helices in membrane proteins: studies with bacterial diacylglycerol kinase. AB - Hydropathy plots have problems in identifying the sequences of transmembrane (TM) alpha-helices when they contain charged residues. Here we show that fluorescence spectroscopy can be used to define the ends of TM alpha-helices. Diacylglycerol kinase (DGK) from Escherichia coli contains three transmembrane (TM) alpha helices per monomer. We have used fluorescence techniques to define the region of the putative first TM helix (TM1) that spans the hydrophobic core of the lipid bilayer surrounding DGK in reconstituted membranes. Single Cys mutants were introduced into TM1 and flanking sites, in a mutant of DGK lacking the two native Cys residues. Introduction of Cys residues into the region between residues 28 and 34 resulted in mutants with low activities, due to a combination of reduced affinities for ATP and diacylglycerol and a reduced maximum rate. Cross-linking experiments showed that the low-activity mutants were present largely in the normal, trimeric form after reconstitution. Fluorescence emission maxima for the Cys mutants labeled with N-((2-(iodoacetoxy)ethyl)-N-methyl)amino-7-nitrobenz-2 oxa-1,3-diazole (IANBD) reconstituted into bilayers of dioleoylphosphatidylcholine varied with position, suggesting that the region of TM1 spanning the hydrophobic core of the bilayer runs from Glu-28 on the cytoplasmic side to Asp-49 or Val-50 on the periplasmic side. This locates the charged/polar cluster 32RQE34 within the hydrophobic core of the bilayer. Fluorescence quenching experiments agree with this assignment for TM1, the results showing a periodicity consistent with distinct stripes of amino acid residues along the length of the helix, the stripes facing the lipid bilayer and facing the rest of the protein, respectively. The residues located close to the glycerol backbone region of the bilayer remained the same when the lipid fatty acyl chain length was changed in the range C14 to C22, showing that hydrophobic matching between the protein and the surrounding lipid bilayer is highly efficient. PMID- 17722886 TI - Lambda Red-mediated mutagenesis and efficient large scale affinity purification of the Escherichia coli NADH:ubiquinone oxidoreductase (complex I). AB - The proton-pumping NADH:ubiquinone oxidoreductase, the respiratory complex I, couples the transfer of electrons from NADH to ubiquinone with the translocation of protons across the membrane. The Escherichia coli complex I consists of 13 different subunits named NuoA-N (from NADH:ubiquinone oxidoreductase), that are coded by the genes of the nuo-operon. Genetic manipulation of the operon is difficult due to its enormous size. The enzymatic activity of variants is obscured by an alternative NADH dehydrogenase, and purification of the variants is hampered by their instability. To overcome these problems the entire E. coli nuo-operon was cloned and placed under control of the l-arabinose inducible promoter ParaBAD. The exposed N-terminus of subunit NuoF was chosen for engineering the complex with a hexahistidine-tag by lambda-Red-mediated recombineering. Overproduction of the complex from this construct in a strain which is devoid of any membrane-bound NADH dehydrogenase led to the assembly of a catalytically active complex causing the entire NADH oxidase activity of the cytoplasmic membranes. After solubilization with dodecyl maltoside the engineered complex binds to a Ni2+-iminodiacetic acid matrix allowing the purification of approximately 11 mg of complex I from 25 g of cells. The preparation is pure and monodisperse and comprises all known subunits and cofactors. It contains more lipids than earlier preparations due to the gentle and fast purification procedure. After reconstitution in proteoliposomes it couples the electron transfer with proton translocation in an inhibitor sensitive manner, thus meeting all prerequisites for structural and functional studies. PMID- 17722885 TI - Isolation and characterization of glutaminyl cyclases from Drosophila: evidence for enzyme forms with different subcellular localization. AB - Glutaminyl cyclases (QCs) present in plants and vertebrates catalyze the formation of pyroglutamic acid (pGlu) from N-terminal glutamine. Pyroglutamyl hormones also identified in invertebrates imply the involvement of QC activity during their posttranslational maturation. Database mining led to the identification of two genes in Drosophila, which putatively encode QCs, CG32412 (DromeQC) and CG5976 (isoDromeQC). Analysis of their primary structure suggests different subcellular localizations. While DromeQC appeared to be secreted due to an N-terminal signal peptide, isoDromeQC contains either an N-terminal mitochondrial targeting or a secretion signal due to generation of different transcripts from gene CG5976. According to the prediction, homologous expression of the corresponding cDNAs in S2 cells revealed either secreted protein in the medium or intracellular QC activity. Subcellular fractionation and immunochemistry support export of isoDromeQC into the mitochondrion. For enzymatic characterization, DromeQC and isoDromeQC were expressed heterologously in Pichia pastoris and Escherichia coli, respectively. Compared to mammalian QCs, the specificity constants were about 1 order of magnitude lower for most of the analyzed substrates. The pH dependence of the specificity constant was similar for both enzymes, indicating the necessity of an unprotonated substrate amino group and two protonated groups of the enzyme, resulting in an asymmetric bell shaped characteristic. The determination of the metal content of DromeQC revealed equimolar protein-bound zinc. These results prove conserved enzymatic mechanisms between QCs from invertebrates and mammals. Drosophila is the first organism for which isoenzymes of glutaminyl cyclase have been isolated. The identification of a mitochondrial QC points toward yet undiscovered physiological functions of these enzymes. PMID- 17722888 TI - Ring closure reaction dynamics of diarylethene derivatives in solution. AB - Photochromic ring closure reaction dynamics of 1,2-bis(2-methylbenzo[b]thiophen-3 yl)hexafluoro cyclopentene and its derivatives in solution has been studied by femtosecond time-resolved fluorescence. Time-resolved spontaneous fluorescence of the open isomer reveals a fast component of around 1 ps and a slow component on the order of 100 ps. Fluorescence time profiles, reaction quantum yields, and relative populations of the parallel (C(s) symmetry) and antiparallel (C(2) symmetry) conformations indicate that both time components are attributable mostly to the C(2) conformer that undergoes the ring closure reaction. The fast component is assigned to the direct ring closure reaction, and the slow component is assigned to the reaction through conformation change. Time constants of the slow component for the derivatives are inversely proportional to the reaction quantum yields, suggesting that the rate of the conformational dynamics is comparable to the rate of other population relaxation processes. The relative amplitude and exact time constant of the fast component depend on the detection wavelength displaying a higher relative amplitude with shorter time constant at longer wavelengths. The results allow us to propose a conformational inhomogeneity model, in which a broad distribution of conformations of the open isomers in the ground state is projected into two minima in the excited electronic potential surface to lead to the slow and the fast reaction pathways. PMID- 17722887 TI - Thermodynamic studies of bromine-iodine competition in the formation of NaSnXYZ (X, Y, Z, = Br or I) complexes. AB - The thermodynamic studies of NaSnXYZ (X, Y, Z = Br or I) are presented. The determined theoretical structures and vibrational properties lead to improved experimental values of dissociation enthalpies and entropies. The ab initio thermodynamic data is also reported. The nature of bonding of binary SnXY-NaZ complexes is discussed with the emphasis on differences between bromine and iodine. PMID- 17722890 TI - Gas-phase reactions and rearrangements of alkyl esters with H3O+, NO+, and O2*+: a selected ion flow tube study. AB - Selected ion flow tube mass spectrometry (SIFT-MS) has been employed to study the ion-molecule reactions of 17 alkyl esters reacting with the common SIFT-MS reagent ions, H3O+, H3O+.nH2O (n = 1, 2, 3), NO+, and O2+. The majority of reactions were observed to proceed at or near collision rate, with the exception of H3O+.3H2O, which was found to be slow for 8 of 17 alkyl esters. Unexpected product ions in the form of the parent carboxylic acid cation were observed to arise from the H3O+ and NO+ reactions of some alkyl esters. The observed reactions have been probed by the ab initio CBS-4M and G2(MP2,SVP) methods. The postulated reaction pathway involves a 1,5 H atom migration from a beta-carbon onto the carbonyl oxygen. PMID- 17722889 TI - Methylsalicylate: a rotational spectroscopy study. AB - We report the free-jet rotational spectra of methylsalicylate, a molecule with a possible tautomeric and conformational equilibrium. In the ground electronic state, the molecule adopts a form stabilized by an intramolecular hydrogen bond between the phenolic hydrogen and the carbonylic oxygen, and this structure is characterized as the lowest-energy form by quantum chemical calculations. All rotational transitions are split because of the internal rotation of the methyl group, and the value of the barrier for this motion was determined to be V(3) = 5.38 kJ mol(-1). PMID- 17722891 TI - Coherent control of population transfer in Rydberg atoms via chirped microwave pulses. AB - We present a comprehensive and ab initio nonperturbative investigation of the coherent population transfer among the 3D high-lying Rydberg hydrogen and alkali atomic states via linearly polarized chirped microwave pulses. The time-dependent Schrodinger equation for the dynamical evolution of Rydberg atoms is accurately and efficiently solved by means of the time-dependent generalized pseudospectral method. For atomic H, the population transfer from n = 35 to 30 with nearly 100% efficiency is achieved by means of the sequential two-photon Deltan = -1 transitions. The calculation fully utilizes all of the available orbital angular momentum l states for a given n, and the interference pattern and population evolution dynamics of individual l states are analyzed in detail. It is shown that the coherent control of the population transfer from the high n to the low n states can be accomplished by the optimization of the chirping parameters and microwave field strength. Similar analysis is performed for the Na atom, where the alkali atomic structure is described by an accurate model potential. We found that while the global population transfer pattern is qualitatively similar, there are significant differences in the dynamical response of atomic H and Na to the chirped microwave fields. Due to the degeneracy of the l states (for a given n) in unperturbed atomic H, the population transfer involves significant coupling and interference among a number of low-lying l states. For the case of Na atoms, however, the population transfer from the n to (n - 1) state is dominated by a single channel, namely, from the |n,l = 0> to the |n - 1,l = 0> state. PMID- 17722893 TI - Nonlinear optical and two-photon absorption properties of octupolar tris(bipyridyl)metal complexes. AB - The linear (absorption and emission) and nonlinear optical (NLO) properties of a series of D(3) [(Fe(II), Ru(II), Ni(II), Cu(II), Zn(II)] octupolar metal complexes featuring the 4,4'-bis[(dibutylamino)styryl]-2,2'-bipyridine ligand are reported. Zinc(II), nickel(II), and copper(II) complexes exhibit similar absorption spectra in the visible region (lambda(ILCT) = 474-476 nm) which are assigned to intraligand charge-transfer (ILCT) bands. The quadratic and cubic NLO properties are strongly influenced by the nature of the metallic center. Harmonic light scattering studies at lambda = 1.91 microm reveal that these chromophores display large first hyperpolarizabilities beta(1.91) in the range of (211-340) x 10(-30) esu; replacing the Zn(II) metal ion by Ni(II) or Cu(II) results in a decrease of the static beta(0) coefficient by a factor of 1.5-1.6. Z-scan measurements at 765 and 965 nm reveal relatively large two-photon absorption cross-sections [650 < sigma(2) < 2200 GM], showing that both beta and sigma(2) values can be tuned by simple modification of the metal ion. PMID- 17722892 TI - Second hyperpolarizabilities of singlet polycyclic diphenalenyl radicals: effects of the nature of the central heterocyclic ring and substitution to diphenalenyl rings. AB - Adopting density functional theory and a hybrid exchange-correlation functional, the relationship between the second hyperpolarizability (gamma) and the diradical character has been investigated for diphenalenyl-based compounds containing different heterocyclic five-membered central rings (C(4)H(4)X, where X = NH, PH, O, S, CH(2), SiH(2), BH, GaH, C=O, C=S, and C=Se) or substituted by donor (NH(2))/acceptor(NO(2)) groups. It turns out that these structural modifications can tune the diradical character from 0.0 to 0.968 and lead to variations of gamma over more than 1 order of magnitude, demonstrating the controllability of gamma in this family of compounds. In particular, when the central ring is strongly aromatic, the diradical character is larger than 0.7, which is associated with pretty large gamma values except for almost the pure diradical case (y approximately 1). On the other hand, when the aromaticity decreases--or the antiaromaticity increases--the diradical character and the second hyperpolarizability get smaller. These relationships are correlated to structural (bond length alternation) and charge distribution (charge transfer between the phenalenyl rings and the central ring) properties, which account for the relative importance of the resonance diradical, zwitterionic, and quinoid forms. Therefore, the diradical character and the second hyperpolarizability can be controlled by the aromaticity of the ring while the paradigm of the enhancement of gamma for intermediate diradical character is globally verified. Then, upon introducing donor groups, the zwitterionic character increases, leading to closed shell species and small second hyperpolarizabilities. In the case of substitution by acceptor groups, the charge transfer is reduced but the diradical character and the second hyperpolarizability hardly changes. PMID- 17722894 TI - Ion chemistry in cold plasmas of H2 with CH4 and N2. AB - The distributions of ions and neutrals in low-pressure (approximately 10(-2) mbar) DC discharges of pure hydrogen and hydrogen with small admixtures (5%) of CH(4) and N(2) have been determined by mass spectrometry. Besides the mentioned plasma precursors, appreciable amounts of NH(3) and C(2)H(x) hydrocarbons, probably mostly from wall reactions, are detected in the gas phase. Primary ions, formed by electron impact in the glow region, undergo a series of charge transfer and reactive collisions that determine the ultimate ion distribution in the various plasmas. A comparison of the ion mass spectra for the different mixtures, taking into account the mass spectra of neutrals, provides interesting information on the key reactions among ions. The prevalent ion is H3+ in all cases, and the ion chemistry is dominated by protonation reactions of this ion and some of its derivatives. Besides the purely hydrogenic ions, N(2)H+, NH(4)+, and CH(5)+ are found in significant amounts. The only mixed C/N ion clearly identified is protonated acetonitrile C(2)H(4)N+. The results suggest that very little HCN is formed in the plasmas under study. PMID- 17722895 TI - Three-photon absorption cross-section enhancement in two symmetrical fluorene based molecules. AB - In this article, we report the pure three-photon absorption effects of two novel symmetrical fluorene-based molecules with 2D-pi-2D [9,9-diethylhexyl-2,7-bis-(N,N diphenylamine)fluorene] and 2D-D-pi-D-2D [5,5'-(9,9-bis-(2-ethylhexyl)-9H fluorene-2-yl)bis(N,N-diphenylthiophen-2-amine)] structural motifs. The obtained three-photon absorption cross sections, (4.74 +/- 0.01) x 10(-76) and (6.77 +/- 0.02) x 10(-76) cm(6) s(2) for the 2D-pi-2D and 2D-D-pi-D-2D archetypes, respectively, are rather high. The geometries and electronic excitations of the two molecules were systematically studied by the PM3 and ZINDO/S methods. The influence of the different molecular structures on the three-photon absorption cross section is discussed micromechanically. The experimental and theoretical results demonstrate that the transition dipole moment between the ground and final states is the most definitive factor. A new fitting method that is more accurate than those reported previously was used to obtain the 3PA coefficient. PMID- 17722896 TI - *H atom and *OH radical reactions with 5-methylcytosine. AB - The reactions between either a hydrogen atom or a hydroxyl radical and 5 methylcytosine (5-MeCyt) are studied by using the hybrid kinetic energy meta-GGA functional MPW1B95. *H atom and *OH radical addition to positions C5 and C6 of 5 MeCyt, or *OH radical induced H-abstraction from the C5 methyl group, are explored. All systems are optimized in bulk solvent. The data presented show that the barriers to reaction are very low: ca. 7 kcal/mol for the *H atom additions and 1 kcal/mol for the reactions involving the *OH radical. Thermodynamically, the two C6 radical adducts and the *H-abstraction product are the most stable ones. The proton hyperfine coupling constants (HFCC), computed at the IEFPCM/MPW1B95/6-311++G(2d,2p) level, agree well with B3LYP results and available experimental and theoretical data on related thymine and cytosine radicals. PMID- 17722897 TI - Electric field effects on aromatic and aliphatic hydrocarbons: a density functional study. AB - The influence of a uniform static external electric field on some aliphatic and aromatic molecular species is studied within the density functional theory (DFT) employing the 6-311++G(2d,2p) basis set with B3LYP exchange-correlation prescription. The electric field perturbs the molecular geometry but drastically alters the dipole moments and engenders, to a varying degree, the molecular vibrational Stark effect, i.e., shifts in the infrared (IR) vibrational frequencies accompanied by spectral intensity redistribution. For polar molecules, significant negative ("red") and positive ("blue") frequency shifts are observed for field orientations both parallel and antiparallel to their permanent dipole moments. Further, a selective reordering of frontier orbitals is observed to be brought about by moderately intense fields. In particular, molecules having a lowest unoccupied molecular orbital (LUMO) with predominant pi character possess a threshold field beyond which energy gap between the highest occupied molecular orbital (HOMO) and LUMO diminishes rapidly. A time-dependent (TD) DFT analysis reveals that an increase in the applied field strength by and large increases the excitation energies corresponding to significant electronic transitions among frontier MOs with a concomitant decrease in their oscillator strengths. PMID- 17722898 TI - Photodissociation of 1,3,5-triazine: an ab initio and RRKM study. AB - The ab initio/Rice-Ramsperger-Kassel-Marcus (RRKM) approach has been applied to investigate the photodissociation mechanism of 1,3,5-triazine at different wavelengths of the absorbed photon. Reaction pathways leading to various decomposition products have been mapped out at the G3(MP2,CC)//B3LYP level, and then the RRKM and microcanonical variational transition state theories have been applied to compute rate constants for individual reaction steps. Relative product yields (branching ratios) for the dissociation products have been calculated using the steady-state approach. The results show that, after being excited by 275, 248, or 193 nm photons, the triazine molecule isomerizes to an opened-ring structure on the first singlet excited-state potential energy surface (PES), which is followed by relaxation into the ground electronic state via internal conversion. On the contrary, excitation by 285 and 295 nm photons cannot initiate the ring-opening reaction on the excited-state PES, and the molecule relaxes into the energized ring isomer in the ground electronic state. The dissociation reaction starting from the ring isomer is calculated to have branching ratios of various reaction channels significantly different from those for the reaction initiating from the opened-ring structure. The existence of two distinct mechanisms of 1,3,5-triazine photodissociation can explain the inconsistency in the translational energy distributions of HCN moieties at different wavelengths observed experimentally. PMID- 17722899 TI - Selection of a respiratory syncytial virus fusion inhibitor clinical candidate, part 1: improving the pharmacokinetic profile using the structure-property relationship. AB - We previously reported the discovery of substituted benzimidazole fusion inhibitors with nanomolar activity against respiratory syncytial virus (Andries, K.; et al. Antiviral Res. 2003, 60, 209-219). A lead compound of the series was selected for preclinical evaluation. This drug candidate, JNJ-2408068 (formerly R170591, 1), showed long tissue retention times in several species (rat, dog, and monkey), creating cause for concern. We herein describe the optimization program to develop compounds with improved properties in terms of tissue retention. We have identified the aminoethyl-piperidine moiety as being responsible for the long tissue retention time of 1. We have investigated the replacement or the modification of this group, and we suggest that the pKa of this part of the molecules influences both the antiviral activity and the pharmacokinetic profile. We were able to identify new respiratory syncytial virus inhibitors with shorter half-lives in lung tissue. PMID- 17722900 TI - Synthesis and structure-affinity relationships of new 4-(6-iodo-H-imidazo[1,2 a]pyridin-2-yl)-N-dimethylbenzeneamine derivatives as ligands for human beta amyloid plaques. AB - A new and extensive set of 4-(6-iodo-H-imidazo[1,2-a]pyridin-2-yl)-N dimethylbenzeneamine (IMPY) derivatives was synthesized and assayed for affinity toward human Abeta plaques. 6-Ethylthio- (12h), 6-cyano- (12e), 6-nitro- (12f), and 6-p-methoxybenzylthio- (15d) analogues were discovered to have high affinity (KI < 10 nM). However, introduction of a hydrophilic thioether group in the 6 position (15a-c, 15e-g) reduced or abolished affinity. In secondary N-methyl analogues, a bromo substituent in the adjacent ring position (14a) imparted high affinity (KI = 7.4 nM) whereas a methyl substituent did not (14c). The tolerance for nonhydrophilic thioether substituents in the 6-position opens up the possibility of developing new sensitive positron emission tomography radioligands for imaging human Abeta plaques in Alzheimer's disease, especially in view of the amenability of thioethers to be labeled with carbon-11 or fluorine-18 through S alkylation reactions. The structure-activity relationships revealed in this study extends insight into the topography of the binding site for IMPY-like ligands in human Abeta plaques. PMID- 17722902 TI - L-(+)-2-Amino-4-thiophosphonobutyric acid (L-thioAP4), a new potent agonist of group III metabotropic glutamate receptors: increased distal acidity affords enhanced potency. AB - L-2-Amino-4-phosphonobutyric acid (l-AP4), l-2-amino-4-thiophosphonobutyric acid (l-thioAP4), and l-2-amino-4-(hydroxy)phosphinylbutyric acid (desmethylphosphinothricin, DMPT) were synthesized from protected vinylglycine. They were tested as agonists at group III metabotropic glutamate receptors (mGluR) along with phosphinothricin (PT). DMPT and PT display a much lower potency at mGlu4 receptor (EC50 = 4.0 and 1100 microM, respectively) in comparison to l-AP4 (EC50 = 0.08 microM), whereas l-thioAP4 has a 2-fold higher potency (EC50 = 0.039 microM). Similar rank orders of potency were observed at mGlu6,7 and mGlu8 receptors. The higher potency of l-thioAP4 is due to its stronger second acidity compared to l-AP4. These pKa values of 5.56 and 6.88, respectively, were determined using 31P NMR chemical shift variations. The second distal negative charge of l-AP4/l-thioAP4 probably provides stronger binding to specific basic residues of the binding sites of group III mGluRs, which stabilizes the active conformation of the receptor. PMID- 17722901 TI - Second generation tetrahydroquinoline-based protein farnesyltransferase inhibitors as antimalarials. AB - Substituted tetrahydroquinolines (THQs) have been previously identified as inhibitors of mammalian protein farnesyltransferase (PFT). Previously we showed that blocking PFT in the malaria parasite led to cell death and that THQ-based inhibitors are the most potent among several structural classes of PFT inhibitors (PFTIs). We have prepared 266 THQ-based PFTIs and discovered several compounds that inhibit the malarial enzyme in the sub- to low-nanomolar range and that block the growth of the parasite (P. falciparum) in the low-nanomolar range. This body of structure-activity data can be rationalized in most cases by consideration of the X-ray structure of one of the THQs bound to mammalian PFT together with a homology structural model of the malarial enzyme. The results of this study provide the basis for selection of antimalarial PFTIs for further evaluation in preclinical drug discovery assays. PMID- 17722904 TI - Pharmacological characteristics and binding modes of caracurine V analogues and related compounds at the neuronal alpha7 nicotinic acetylcholine receptor. AB - The pharmacological properties of bisquaternary caracurine V, iso-caracurine V, and pyrazino[1,2-a;4,5-a']diindole analogues and of the neuromuscular blocking agents alcuronium and toxiferine I have been characterized at numerous ligand gated ion channels. Several of the analogues are potent antagonists of the homomeric alpha7 nicotinic acetylcholine receptor (nAChR), displaying nanomolar binding affinities and inhibiting acetylcholine-evoked signaling through the receptor in a competitive manner. In contrast, they do not display activities at heteromeric neuronal nAChRs and only exhibit weak antagonistic activities at the related 5-HT3A serotonin receptor. In a mutagenesis study, five selected analogues have been demonstrated to bind to the orthosteric site of the alpha7 nAChR. The binding site of the compounds overlaps with that of the standard alpha7 antagonist methyllycaconitine, the binding of them being centered in a cation-pi interaction between the quaternary nitrogen atom of the ligand and the Trp149 residue in the receptor, with additional key contributions from other aromatic receptor residues such as Tyr188, Tyr195, and Trp55. PMID- 17722903 TI - Novel substituted (pyridin-3-yl)phenyloxazolidinones: antibacterial agents with reduced activity against monoamine oxidase A and increased solubility. AB - Oxazolidinones represent a new and promising class of antibacterial agents. Current research in this area is mainly concentrated on improving the safety profile and the antibacterial spectrum. Oxazolidinones bearing a (pyridin-3 yl)phenyl moiety (e.g., 3) generally show improved antibacterial activity compared to linezolid but suffer from potent monoamine oxidase A (MAO-A) inhibition and low solubility. We now disclose the finding that new analogues of 3 with acyclic substituents on the pyridyl moiety exhibit excellent activity against Gram-positive pathogens, including linezolid-resistant Streptococcus pneumoniae. Generally, more bulky substituents yielded significantly reduced MAO A inhibition relative to the unsubstituted compound 3. The MAO-A SAR can be rationalized on the basis of docking studies using a MAO-A/MAO-B homology model. Solubility was enhanced with incorporation of polar groups. One optimized analogue, compound 13, showed low clearance in the rat and efficacy against S. pneumoniae in a mouse pneumonia model. PMID- 17722905 TI - Synthesis and biological activities of new checkpoint kinase 1 inhibitors structurally related to granulatimide. AB - In the course of structure-activity relationship studies on granulatimide analogues, new pyrrolo[3,4-c]carbazoles in which the imidazole heterocycle has been replaced by a five- or a six-membered ring bearing one or two carbonyl functions have been synthesized. Their checkpoint kinase 1 (Chk1) inhibitory properties and their in vitro antiproliferative activities toward three tumor cell lines-murine leukemia L1210 and human colon carcinoma HT29 and HCT116 have been determined. The results of molecular modeling in the ATP binding pocket of Chk1 are described. Among the newly synthesized compounds, compounds 13 and 16, in which the imidazole was replaced by a quinone and a hydroquinone and which bear a hydroxy group on the indole moiety, are the most potent Chk1 inhibitors in this series with IC50 values of 27 and 23 nM, respectively. PMID- 17722906 TI - The disruption of hepatic cytochrome p450 reductase alters mouse lipid metabolism. AB - To elucidate the role of hepatic cytochrome P450 oxidoreductase (POR) in lipid metabolism, we characterized perturbations in lipid homeostasis in a mouse model deficient in liver POR. Using an integrative approach in which transcriptomics, lipidomics, and various bioinformatic algorithms were employed, a disruption in liver lipid mobilization, oxidation, and electron transport functions were identified. Analyzing the promoters of genes in these biological processes identified common binding motifs for nuclear receptors sensitive to lipid status, while Srebp-1c binding sites were only identified in genes involved in lipid metabolism. POR-null mice had drastic increases in hepatic lipid content (diacylglycerols, triacylglycerols, phosphatidylcholine, and cholesterol esters) and a specific enrichment in n-7 and n-9 monounsaturated fatty acids (FAs). It was found that while transporters involved in peroxisomal FA oxidation were induced, mitochondrial oxidation appeared to be more tightly controlled, supporting the increase in monounsaturated FAs. Genes coding for hepatic transporters were differentially expressed, where lipid uptake was induced and efflux repressed, indicating that in the absence of hepatic POR the liver serves as a lipid reservoir. Furthermore, while significant changes in intestinal gene expression were found in POR-deficient mice, only minor changes to plasma and intestinal lipid content were observed. Thus, while liver POR plays an important role regulating gene expression and lipid metabolism locally, the hepatic deficiency of this enzyme reverberates throughout the biological system and produces a coordinated response to the low levels of circulating cholesterol and bile. PMID- 17722907 TI - A molecular dynamics calculations of hole transfer rates in DNA strands. AB - A computational model, which includes both tunneling and thermal hopping mechanisms, has been applied to study the charge transfer in DNA (GC)n and (AT)n strands. The calculations revealed the crucial role played by the A or G NH2 group vibrations in the hole transfer in both types of strands. Charge-transfer rates in the two strands have been determined based on the molecular dynamics calculations. They are in good agreement with the available experimental data. The modeling approach used here may be employed in the theoretical study of the charge transfer in natural and artificial DNA strands containing AT and GC pairs. PMID- 17722908 TI - Comprehensive experimental and theoretical study of chemical equilibria in the reacting system of the tert-amyl methyl ether synthesis. AB - The chemical equilibrium of the reactive system (methanol+isoamylenes<-->methyl tert-amyl ether) was studied in the temperature range 298-393 K in the liquid phase using the method of sealed ampoules as well as in the gaseous phase using a tubular flow reactor in the temperature range 355-378 K. In both cases, a cation exchanger Amberlist-15 was used as a heterogeneous catalyst. The reactive system of the methyl tert-amyl ether synthesis exhibits a strong nonideal behavior of the mixture compounds in the liquid phase. The knowledge of the activity coefficients is required in order to obtain the thermodynamic equilibrium constants Ka. Two well-established procedures, UNIFAC and COSMO-RS, have been used to assess activity coefficients of the reaction participants in the liquid phase. Thermodynamic equilibrium constants KP measured in the gaseous phase together with the vapor pressures of the pure compounds have been used to obtain Ka in the liquid phase on a consistent experimental basis in order to check the results obtained from the UNIFAC and COSMO-RS methods. Enthalpies of reactions DeltarH degrees of the methyl tert-amyl ether synthesis reaction in the gaseous and in the liquid phase were obtained from temperature dependences of the corresponding thermodynamic equilibrium constants. Consistency of the experimental data of DeltarH degrees was verified with help of enthalpies of formation and enthalpies of vaporization of methyl tert-amyl ether, methanol, and methyl-butenes, available from the literature. For the sake of comparison, high level ab initio calculations of the reaction participants have been performed using the Gaussian-03 program package. Absolute electronic energy values, normal frequencies (harmonic approximation), and moments of inertia of the molecules have been obtained using G2(MP2), G3(MP2), and G3 levels. Using these results, calculated equilibrium constants and the enthalpy of reaction of the methyl tert amyl ether synthesis in the gaseous phase based on the principles of statistical thermodynamics are found to be in acceptable agreement with the data obtained from the thermochemical measurements. PMID- 17722909 TI - Equations of state for fluids: empirical temperature dependence of the second virial coefficients. AB - In this paper, an empirical dependence of the second virial coefficients is derived from equations of state. The second virial coefficient B2 is found to be a linear function of 1/T1+beta, where T is the temperature and beta is a constant and has different value for different substances. Excellent experimental supports to this relationship are reported for nonpolar fluids, polar fluids, heavy globular molecule fluids, and quantum fluid He-4. PMID- 17722910 TI - Organic crystal fibers aligned into oriented bundles with polarized emission. AB - We demonstrate a simple method for growing organic crystal fiber bundles as long as centimeters by controlling the shape and dimension of the evaporation channel of the chloroform solution of N,N'-bis(1-ethylpropyl)-3,4,9,10 perylenebis(dicarboximide) (EPPTC). The capillary effect induces a thin solution film (capillary film) on the wall of the evaporation channel, and fast evaporation of the solvent gives rise to a concentration gradient along the channel. Thus, the strong pi-stacking between the EPPTC molecules in the capillary film results in formation of crystal fibers. Nearly linearly polarized emission centered around 620 nm has been detected from these crystal fibers under optical excitation. Measurements of the electron diffraction pattern and optical microscopic properties show well-defined stacking of the molecules in the crystal fibers with excellent alignment. PMID- 17722911 TI - Raman scattering study of high-pressure phase transition in thiourea. AB - A high-pressure Raman spectroscopic study of phase transitions in thiourea is reported. The changes in the Raman spectra with increasing and decreasing pressure have been followed to a maximum pressure of approximately 11 GPa. We observe several changes in the spectra including splitting of modes, appearance of new modes, and sudden change in the slope of the frequency-pressure curve at several pressures. On the basis of this study, we propose the existence of three more transitions in this system to phases VII, VIII, and IX at approximately 1, 3, and 6.1 GPa, respectively, in addition to the V-VI phase transition at 0.35 GPa reported earlier. All the transitions have been found to be completely reversible. We interpret these changes in terms of symmetry-lowering phase transitions. PMID- 17722912 TI - A-B diblock copolymer micelles: effects of soluble-block length and component compatibility. AB - Micellization of a diblock copolymer in dilute solution is studied by dissipative particle dynamics. The influence of the compatibility between blocks A and B and the interaction between the insoluble block and solvent on aggregation number P and micellar core radius Rc are examined. The micelle size distribution is obtained, and it is quite polydisperse. Different from the scaling theory for starlike micelles, the mean aggregation number based on weight average

w decreases with increasing soluble-block length NA and the power law relation can be obtained,

w approximately NA(-alpha). Similarly, the micellar core radius declines with NA, following Rc approximately NA(-beta) with beta=alpha/3. However, the exponent depends on the mutual compatibility between soluble and insoluble blocks. For the same composition, the incompatible diblocks form a smaller micelle and its aggregation number declines with a smaller exponent alpha. When NA approximately NB, the micelles deviate significantly from the spherical shape and solvophilic blocks are observed to be entrapped in the solvophobic core for compatible diblocks. PMID- 17722913 TI - Theoretical study of solvent effects on the thermodynamics of iron(III) [tetrakis(pentafluorophenyl)]porphyrin chloride dissociation. AB - A quasichemical method that combines ab initio treatment of explicit solvent with dielectric continuum models has been used to study the origin of a strong effect of methanol on the extent of iron(III) [tetrakis(pentafluorophenyl)]porphyrin chloride dissociation in acetonitrile-methanol solutions. It is shown that the dissociation is energetically more favorable in methanol than in acetonitrile primarily because of the strong specific interactions between the chloride anion and the solvent methanol molecules in its first solvation shell. These interactions are weaker in acetonitrile. The final estimate for the difference in the dissociation free energies in methanol and acetonitrile is -23 kJ/mol, in a good agreement with the experimental value of -21 kJ/mol. Energy decomposition analysis of chloride-solvent interactions suggests that stronger chloride methanol binding is a result of the contribution of charge delocalization effects to the chloride-methanol interactions. PMID- 17722914 TI - Homogeneous nucleation temperatures in aqueous mixed salt solutions. AB - This is the first report on the measurement of homogeneous nucleation temperature, TH, in the presence of aqueous mixed salt systems of varying compositions and ionic strengths. The TH,m (TH value in aqueous mixed salt system) data for these systems have been analyzed in terms of a simple empirical equation. The TH,m values in simple aqueous mixed salts like NaCl-KCl can be approximated by linear summation of the products of ionic strength fraction and the TH values of pure salt solutions at the same ionic strength as that of the mixture. The empirical parameter, q0, indicating ionic interaction is related to the viscosity B-coefficients. The TH,m data, though correlated on the basis of the B-coefficients also depends upon the mixing of two ions of like charges. Further, a linear correlation exists between the q0 parameter and self-diffusion coefficient, D0, of the ionic solute. The q0 parameter is also well correlated with the rotational correlation time, tauch/tauc0 of the ionic species involved in the mixtures. It is possible to compute TH,m for the salt mixtures with no common ions from the knowledge of the TH,m values of the salt mixtures with common ions. PMID- 17722915 TI - Novel dinuclear uranyl complexes with asymmetric schiff base ligands: synthesis, structural characterization, reactivity, and extraction studies. AB - The reaction of uranyl nitrate with asymmetric [3O, N] Schiff base ligands in the presence of base yields dinuclear uranyl complexes, [UO2(HL1)]2.DMF (1), [UO2(HL2)]2.2DMF.H2O (2), and [UO2(HL3)]2.2DMF (3) with 3-(2 hydroxybenzylideneamino)propane-1,2-diol (H3L1), 4-((2,3 dihydroxypropylimino)methyl)benzene-1,3-diol (H3L2), and 3-(3,5-di-tert-butyl-2 hydroxybenzylideneamino)propane-1,2-diol (H3L3), respectively. All complexes exhibit a symmetric U2O2 core featuring a distorted pentagonal bipyramidal geometry around each uranyl center. The hydroxyl groups on the ligands are attached to the uranyl ion in chelating, bridging, and coordinate covalent bonds. Distortion in the backbone is more pronounced in 1, where the phenyl groups are on the same side of the planar U2O2 core. The phenyl groups are present on the opposite side of U2O2 core in 2 and 3 due to electronic and steric effects. A similar hydrogen-bonding pattern is observed in the solid-state structures of 1 and 3 with terminal hydroxyl groups and DMF molecules, resulting in discrete molecules. Free aryl hydroxyl groups and water molecules in 2 give rise to a two dimensional network with water molecules in the channels of an extended corrugated sheet structure. Compound 1 in the presence of excess Ag(NO3) yields {[(UO2)(NO3)(C6H4OCOO)](NH(CH2CH3)3)}2 (4), where the geometry around the uranyl center is hexagonal bipyrimidal. Two-phase extraction studies of uranium from aqueous media employing H3L3 indicate 99% reduction of uranyl ion at higher pH. PMID- 17722916 TI - Controlled synthesis of the ZnWO4 nanostructure and effects on the photocatalytic performance. AB - ZnWO4 photocatalysts with various morphologies were synthesized by a hydrothermal process. The effects of hydrothermal temperature and time on the crystallinity and morphology of ZnWO4 catalyst were investigated. The crystallinity was enhanced with the increase of hydrothermal temperature and hydrothermal time. The formation of ZnWO4 nanoparticles was controlled via kinetic process above 160 degrees C, and ZnWO4 nanorods with a highly [100]-preferred orientation formed via the thermodynamically control process in the temperature range of 120-140 degrees C. The morphology and crystallinity of ZnWO4 photocatalyst have a significant influence on the photocatalytic activity for aqueous Rhodamine B and gaseous formaldehyde degradation. ZnWO4 nanorod catalyst showed a much higher photocatalytic activity than the nanoparticle one. The enhanced photocatalytic activity can be attributed to the anisotropic structure of nanorod. PMID- 17722917 TI - Metal-ion-dependent GFP emission in vivo by combining a circularly permutated green fluorescent protein with an engineered metal-ion-binding coiled-coil. AB - Coordination of metal ions significantly contributes to protein structures and functions. Here we constructed a fusion protein, consisting of a de novo designed, metal-ion-binding, trimeric coiled-coil and a circularly permutated green fluorescent protein (cpGFP), where the fluorescent emission from cpGFP was induced by metal ion coordination to the coiled-coil. A circularly permutated GFP, (191)cpGFP(190), was constructed by connecting the original N- and C-termini of GFP(UV) by a GGSGG linker and cleaving it between Asp(190) and Gly(191). The metal-ion-binding coiled-coil, IZ-HH, was designed to have three alpha-helical structures, with 12 His residues in the hydrophobic core of the coiled-coil structure. IZ-HH exhibited an unfolded structure, whereas it formed the trimeric coiled-coil structure in the presence of divalent metal ions, such as Cu(2+), Ni(2+), or Zn(2+). The fusion protein (191)cpGFP(190)-IZ-HH was constructed, in which (191)cpGFP(190) was inserted between the second and third alpha-helices of IZ-HH. Escherichia coli cells, expressing (191)cpGFP(190)-IZ-HH, exhibited strong fluorescence when the Cu(2+) and Zn(2+) ions were present in the medium, indicating that they passed through the cell membrane and induced the proper folding of the (191)cpGFP(190) domain. This strategy, in which protein function is regulated by a metal-ion-responsive coiled-coil, should be applicable to the design of various metal-ion-responsive, nonnatural proteins that work both in vitro and in vivo. PMID- 17722918 TI - Hydrogen-bonding and pi-pi base-stacking interactions are coupled in DNA, as suggested by calculated and experimental trans-Hbond deuterium isotope shifts. PMID- 17722920 TI - A single-point mutation converts the highly amyloidogenic human islet amyloid polypeptide into a potent fibrillization inhibitor. PMID- 17722919 TI - Identification of a selective small-molecule ligand for HIV-1 frameshift-inducing stem-loop RNA from an 11,325 member resin bound dynamic combinatorial library. PMID- 17722921 TI - The electronic structure of the H-cluster in the [FeFe]-hydrogenase from Desulfovibrio desulfuricans: a Q-band 57Fe-ENDOR and HYSCORE study. AB - The active site of the (57)Fe-enriched [FeFe]-hydrogenase (i.e., the "H-cluster") from Desulfovibrio desulfuricans has been examined using advanced pulse EPR methods at X- and Q-band frequencies. For both the active oxidized state (H(ox)) and the CO inhibited form (H(ox)-CO) all six (57)Fe hyperfine couplings were detected. The analysis shows that the apparent spin density extends over the whole H-cluster. The investigations revealed different hyperfine couplings of all six (57)Fe nuclei in the H-cluster of the H(ox)-CO state. Four large 57Fe hyperfine couplings in the range 20-40 MHz were found (using pulse ENDOR and TRIPLE methods) and were assigned to the [4Fe-4S](H) (cubane) subcluster. Two weak (57)Fe hyperfine couplings below 5 MHz were identified using Q-band HYSCORE spectroscopy and were assigned to the [2Fe](H) subcluster. For the H(ox) state only two different 57Fe hyperfine couplings in the range 10-13 MHz were detected using pulse ENDOR. An (57)Fe line broadening analysis of the X-band CW EPR spectrum indicated, however, that all six (57)Fe nuclei in the H-cluster are contributing to the hyperfine pattern. It is concluded that in both states the binuclear subcluster [2Fe](H) assumes a [Fe(I)Fe(II)] redox configuration where the paramagnetic Fe(I) atom is attached to the [4Fe-4S](H) subcluster. The (57)Fe hyperfine interactions of the formally diamagnetic [4Fe-4S](H) are due to an exchange interaction between the two subclusters as has been discussed earlier by Popescu and Munck [Popescu, C.V.; Munck, E., J. Am. Chem. Soc. 1999, 121, 7877 7884]. This exchange coupling is strongly enhanced by binding of the extrinsic CO ligand. Binding of the dihydrogen substrate may induce a similar effect, and it is therefore proposed that the observed modulation of the electronic structure by the changing ligand surrounding plays an important role in the catalytic mechanism of [FeFe]-hydrogenase. PMID- 17722923 TI - Advancing decal-transfer lithography with a reusable PDMS-coated nanoscale stamp. PMID- 17722922 TI - An exchange-free measure of 15N transverse relaxation: an NMR spectroscopy application to the study of a folding intermediate with pervasive chemical exchange. AB - A series of experiments are presented that provide an exchange-free measure of dipole-dipole (15)N transverse relaxation, R(dd), that can then be substituted for (15)N R(1rho) or R(2) rates in the study of internal protein dynamics. The method is predicated on the measurement of a series of relaxation rates involving (1)H-(15)N longitudinal order, anti-phase (1)H and (15)N single-quantum coherences, and (1)H-(15)N multiple quantum coherences; the relaxation rates of all coherences are measured under conditions of spin-locking. Results from detailed simulations and experiments on a number of protein systems establish that R(dd) values are independent of exchange and systematic errors from dipolar interactions with proximal protons are calculated to be less than 1-2%, on average, for applications to perdeuterated proteins. Simulations further indicate that the methodology is rather insensitive to the exact level of deuteration so long as proteins are reasonably highly deuterated (>50%). The utility of the methodology is demonstrated with applications involving protein L, ubiquitin, and a stabilized folding intermediate of apocytochrome b(562) that shows large contributions to (15)N R(1rho) relaxation from chemical exchange. PMID- 17722924 TI - Mechanism of water photooxidation reaction at atomically flat TiO2 (rutile) (110) and (100) surfaces: dependence on solution pH. AB - The mechanism of water photooxidation reaction at atomically flat n-TiO(2) (rutile) surfaces was investigated in aqueous solutions of various pH values, using photoluminescence (PL) measurements. The PL bands, which peaked at around 810 and 840 nm for the (110) and (100) surfaces, respectively, were assigned to radiative transitions between conduction-band electrons and surface-trapped holes (STH), [Ti-O=Ti(2)](s)+, formed at triply coordinated (normal) O atoms at the surface lattice. The PL intensity (I(PL)) decreased stepwise with increasing solution pH, namely, it sharply decreased at around pH 4, near the point of zero charge of TiO(2) (about 5), and then rapidly decreased to zero near pH 13. The first sharp decrease around pH 4 is attributed to the increased rate of nucleophilic attack of a water molecule to a hole at a site of surface bridging oxygen (Ti-O-Ti), the density of which increases with increasing pH. The nucleophilic attack is regarded as the main initiating step of the water oxidation reaction in low and intermediate pH. The high PL intensity at low pH is ascribed to slow nucleophilic attack owing to a very low density of Ti-O-Ti by its protonation at the low pH. The second sharp decrease near pH 13 is attributed to formation of surface anionic species like Ti-O- which can be readily oxidized by photogenerated holes. Interrelations between reaction intermediates proposed in this work and those reported by time-resolved laser spectroscopy are discussed. PMID- 17722925 TI - Molecular recognition and screening using a 15N group selective STD NMR method. AB - We present a novel saturation transfer difference (STD) experiment where group selective (GS) saturation of amide protons in (15)N labeled hosts is achieved. It is demonstrated that a train of BIRD(d) pulses that inverts only protons attached to (15)N indeed results in saturation of the amide protons, while the background proton magnetization is much less affected. The undesired effect of partial saturation of the unlabeled protons can be completely cancelled out in difference spectra by switching the (15)N carrier between the on- and the off-resonance frequencies. As a result, clean and artifact-free STD spectra are obtained without the need of time-consuming optimization of experimental parameters and acquiring control spectra in the absence of the host. The use of the (15)N-GS STD experiment is demonstrated for the case of a glycopeptide antibiotic (dimeric eremomycin)-cell-wall analogue peptide (N-Ac-D-Ala) model system where the host and guest (1)H signals overlap. The application seems feasible for ligand screening against proteins without the prerequisite of a clean on-resonance frequency or defined ligand library. The new experiment can be used as the basis for studying intermolecular interactions where the standard STD experiment is difficult to optimize. PMID- 17722927 TI - Dissociation of DNA-histone assemblies resulting from protein side-chain functionalization. PMID- 17722926 TI - Carbon dots for multiphoton bioimaging. PMID- 17722928 TI - Alternating copolymerization of epoxides and cyclic anhydrides: an improved route to aliphatic polyesters. PMID- 17722930 TI - Formation of nanoparticles by intramolecular cross-linking: following the reaction progress of single polymer chains by atomic force microscopy. PMID- 17722929 TI - Nanosized (mu12-Pt)Pd164-xPtx(CO)72(PPh3)20 (x approximately 7) containing Pt centered four-shell 165-atom Pd-Pt core with unprecedented intershell bridging carbonyl ligands: comparative analysis of icosahedral shell-growth patterns with geometrically related Pd145(CO)x(PEt3)30 (x approximately 60) containing capped three-shell Pd145 core. AB - Presented herein are the preparation and crystallographic/microanalytical/magnetic/spectroscopic characterization of the Pt-centered four-shell 165-atom Pd-Pt cluster, (mu(12)-Pt)Pd(164 x)Pt(x)(CO)(72)(PPh(3))(20) (x approximately 7), 1, that replaces the geometrically related capped three-shell icosahedral Pd(145) cluster, Pd(145)(CO)(x)(PEt(3))(30) (x approximately 60), 2, as the largest crystallographically determined discrete transition metal cluster with direct metal-metal bonding. A detailed comparison of their shell-growth patterns gives rise to important stereochemical implications concerning completely unexpected structural dissimilarities as well as similarities and provides new insight concerning possible synthetic approaches for generation of multi-shell metal clusters. 1 was reproducibly prepared in small yields (<10%) from the reaction of Pd(10)(CO)(12)(PPh(3))(6) with Pt(CO)(2)(PPh(3))(2). Its 165-atom metal-core geometry and 20 PPh(3) and 72 CO ligands were established from a low-temperature (100 K) CCD X-ray diffraction study. The well-determined crystal structure is attributed largely to 1 possessing cubic T(h) (2/m3) site symmetry, which is the highest crystallographic subgroup of the noncrystallographic pseudo-icosahedral I(h) (2/m35) symmetry. The "full" four-shell Pd-Pt anatomy of 1 consists of: (a) shell 1 with the centered (mu(12)-Pt) atom encapsulated by the 12-atom icosahedral Pt(x)Pd(12-x) cage, x = 1.2(3); (b) shell 2 with the 42-atom nu(2) icosahedral Pt(x)Pd(42-x) cage, x = 3.5(5); (c) shell 3 with the anti-Mackay 60 atom semi-regular rhombicosidodecahedral Pt(x)Pd(60-x) cage, x = 2.2(6); (d) shell 4 with the 50-atom nu(2) pentagonal dodecahedral Pd(50) cage. The total number of crystallographically estimated Pt atoms, 8 +/- 3, which was obtained from least-squares (Pt(x)/Pd(1-x))-occupancy analysis of the X-ray data that conclusively revealed the central atom to be pure Pt (occupancy factor, x = 1.00(3)), is fortuitously in agreement with that of 7.6(7) found from an X-ray Pt/Pd microanalysis (WDS spectrometer) on three crystals of 1. Our utilization of this site-occupancy (Pt(x)Pd(1-x))-analysis for shells 1-3 originated from the microanalytical results; otherwise, the presumed metal-core composition would have been (mu(12)-Pt)Pd(164). [Alternatively, the (mu(12)-Pt)M(164) core-geometry of 1 may be viewed as a pseudo-Ih Pt-centered six-shell successive nu(1) polyhedral system, each with radially equivalent vertex atoms: Pt@M(12)(icosahedron)@M(30)(icosidodecahedron)@M(12)(icosahedron)@M(60)(rhombicos dodecahedron)@M(30)(icosidodecahedron)@M(20)(pentagonal dodecahedron)]. Completely surprising structural dissimilarities between 1 and 2 are: (1) to date 1 is only reproducibly isolated as a heterometallic Pd-Pt cluster with a central Pt instead of Pd atom; (2) the 50 atoms comprising the outer fourth nu(2) pentagonal dodecahedral shell in 1 are less than the 60 atoms of the inner third shell in 1, in contradistinction to shell-by-shell growth processes in all other known shell-based structures; (3) the 10 fewer PR3 ligands in 1 necessitate larger bulky PPh(3) ligands to protect the Pd-Pt core-geometry; (4) the 72 CO ligands consist of six bridging COs within each of the 12 pentagons in shell 4 that are coordinated to intershell metal atoms. SQUID magnetometry measurements showed a single-crystal sample of 1 to be diamagnetic over the entire temperature range of 10-300 K. PMID- 17722931 TI - SnTe nanocrystals: a new example of narrow-gap semiconductor quantum dots. PMID- 17722932 TI - PtCl2-catalyzed rapid access to tetracyclic 2,3-indoline-fused cyclopentenes: reactivity divergent from cationic Au(I) catalysis and synthetic potential. PMID- 17722933 TI - En route to an efficient catalytic asymmetric synthesis of AS-3201. PMID- 17722935 TI - Quantification of two polyacetylenes in Radix Ginseng and roots of related Panax species using a gas chromatography-mass spectrometric method. AB - A sensitive method for quantitating the pharmacologically active polyacetylenes panaxynol and panaxydol in Radix Ginseng was developed using a capillary gas chromatography-mass spectrometric (GC-MS) method. The detection mode of selected ion monitoring (SIM) allowed sensitive and selective quantitation of the two compounds in ginseng. Method validation showed that the GC-MS method has much lower detection and quantitation limits than the high-performance liquid chromatography (HPLC)-UV method. This indicates that GC-MS is particularly useful for the analysis of polyacetylene compounds, which have relatively low abundances compared with ginsenosides in ginseng. Based on the quantitative results of different types of ginseng herbs, it was found that the panaxydol and panaxynol contents were higher in forest ginseng than in cultivated ginseng. This method was further applied to the quantitative analyses of panaxynol and panaxydol in Radix Notoginseng and American ginseng. The ratio of panaxydol to panaxynol can be utilized as a marker for differentiating ginseng, notoginseng, and American ginseng. This study introduces the first GC-MS method for the quantitative analysis of polyacetylenes in herbs of the Panax genus. PMID- 17722936 TI - Formation of nanowire striations driven by Marangoni instability in spin-cast polymer thin films. AB - Parallel striations made of silver nanowires were formed through the Marangoni instability induced during spin casting of poly(2-vinyl pyridine)/silver nanowire/chloroform solutions. The striation patterns of the silver nanowires resembled those obtained from spin casting of the corresponding neat polymer solutions, indicating essentially the same driving mechanism (i.e., the Marangoni instability). The silver nanowires were found to concentrate in the valleys of the striation pattern to balance the nonuniform surface tension distribution in the polymer thin film. The resulting nanowire striation patterns were found to depend on polymer concentration, rotational speed, and nanowire loading. Interestingly, this nanowire striation phenomenon was found to be independent of the substrate characteristics, hydrophobic or hydrophilic. PMID- 17722937 TI - Contact shape controls adhesion of bioinspired fibrillar surfaces. AB - Following a recent bioinspired paradigm, patterned surfaces can exhibit better adhesion than flat contacts. Previous studies have verified that finer contact structures give rise to higher adhesion forces. In this study, we report on the effect of the tip shape, which was varied systematically in fibrillar PDMS surfaces, produced by lithographic and soft-molding methods. For fiber radii between 2.5 and 25 microm, it is found that shape exerts a stronger effect on adhesion than size. The highest adhesion is measured for mushroom-like and spatular terminals, which attain adhesion values 30 times in excess of the flat controls and similar to a gecko toe. These results explain the shapes commonly found in biological systems, and help in the exploration of the parameter space for artificial attachment systems. PMID- 17722939 TI - Controlling the interparticle spacing of Au-salt loaded micelles and Au nanoparticles on flat surfaces. AB - The self-organization of diblock copolymers into micellar structures in an appropriate solvent allows the deposition of well ordered arrays of pure metal and alloy nanoparticles on flat surfaces with narrow distributions in particle size and interparticle spacing. Here we investigated the influence of the materials (substrate and polymer) and deposition parameters (temperature and emersion velocity) on the deposition of metal salt loaded micelles by dip-coating from solution and on the order and inter-particle spacing of the micellar deposits and thus of the metal nanoparticle arrays resulting after plasma removal of the polymer shell. For identical substrate and polymer, variation of the process parameters temperature and emersion velocity enables the controlled modification of the interparticle distance within a certain length regime. Moreover, also the degree of hexagonal order of the final array depends sensitively on these parameters. PMID- 17722938 TI - Wettability and topography of phospholipid DPPC multilayers deposited by spin coating on glass, silicon, and mica slides. AB - The surface free energy of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) layers deposited on glass, silicon, or mica by the spin-coating method was estimated. For this purpose, the advancing and receding contact angles of water, formamide, and diiodomethane were measured, and then two concepts of the interfacial interactions were applied. In the contact angle hysteresis approach, the apparent total surface free energy is calculated from the advancing and receding contact angles of the probe liquids, and in the Lifshitz-van der Waals/acid-base approach, the total surface free energy is calculated from previously determined components of the energy, that is, the apolar Lifshitz-van der Waals and the polar electron-donor and electron-acceptor, which are calculated from the advancing contact angles of the probe liquids alone. Comparison of the results obtained using these two approaches provided more information about changes in the hydrophobic/hydrophilic character of the DPPC layers and, simultaneously, a verification of the approaches. Moreover, the roughness and topography of the investigated layers were also examined by atomic force microscopy measurements. The hydrophilic character of the DPPC layers decreased if up to 0.5 mg of DPPC/mL was used to deposit on the substrates by the spin-coating method. Then it increased and leveled off if up to 2-2.5 mg of DPPC/mL was used. The changes in the energy were correlated with the changes in topography of the surfaces. PMID- 17722940 TI - Self-organization of gold-containing hydrogen-bonded rosette assemblies on graphite surface. AB - The self-organization of supramolecular structures, in particular gold-containing hydrogen-bonded rosettes, on highly oriented pyrolytic graphite (HOPG) surfaces was investigated by tapping-mode atomic force microscopy (TM-AFM) and scanning tunneling microscopy (STM). TM-AFM and high-resolution STM results show that these hydrogen-bonded assemblies self-organize to form highly ordered domains on HOPG surfaces. We find that a subtle change in one of the building blocks induces two different orientations of the assembly with respect to the surface. These results provide information on the control over the construction of supramolecular nanoarchitectures in 2D with the potential for the manufacturing of functional materials based on structural manipulation of molecular components. PMID- 17722941 TI - Conducting polymer diffraction gratings on gold surfaces created by microcontact printing and electropolymerization at submicron length scales. AB - Conducting polymer diffraction gratings on Au substrates have been created using microcontact printing of C18-alkanethiols, followed by electropolymerization of either poly(aniline) (PANI) or poly(3,4-ethylenedioxythiophene) (PEDOT). Soft polymer replicas of simple diffraction grating masters (1200 lines/mm) were used to define the alkanethiol template for polymer growth. Growth of PANI and PEDOT diffraction gratings was followed in real time, through in situ tapping-mode atomic force microscopy, and by monitoring diffraction efficiency (DE) as a function of grating depth. DE increased as grating depth increased, up to a limiting efficiency (13-26%, with white light illumination), defined by the combined optical properties of the grating and the Au substrate, and ultimately limited by the loss of resolution due to coalescence of the polymer films. Grating efficiency is strongly dependent upon the grating depth and the refractive index contrast between the grating material and the surrounding solutions. Both PEDOT and PANI gratings show refractive index changes as a function of applied potential, consistent with changes in refractive index brought about by the doping/dedoping of the conducting polymer. The DE of PANI gratings are strongly dependent on the pH of the superstrate solution; the maximum sensitivity (DeltaDE/DeltapH) is achieved with PANI gratings held at +0.4 V versus Ag/AgCl, where the redox chemistry is dominated by the acid-base equilibrium between the protonated (emeraldine salt) and deprotonated (emeraldine base) forms of PANI. Simulations of DE were conducted for various combinations of conducting polymer refractive index and grating depth, to compute sensitivity parameters, which are maximized when the grating depth is ca. 50% of its maximum obtainable depth. PMID- 17722942 TI - Adsorption of benzene, toluene, and xylenes on monolithic carbon aerogels from dry air flows. AB - Monolithic carbon aerogels were obtained by carbonization of organic aerogels prepared by polymerization of resorcinol and formaldehyde under different conditions. Some carbon aerogels obtained were further CO2-activated. Samples were characterized by gas adsorption, scanning electron microscopy, high resolution transmission electron microscopy, and mechanical tests. Benzene, toluene and xylenes were adsorbed from dry air by using carbon bed columns, obtaining the breakthrough curves. There was no correlation between the amount adsorbed at the breakthrough point and the volume of micropores narrower than 0.7 nm. Conversely, a good linear relationship between the amount adsorbed at the breakthrough point and the total micropore volume up to a mean micropore width of around 1.05 nm was found. In addition, the height of the mass transfer zone decreased with the mean width of the total micropores up to a value of around 1.05-1.10 nm. One of the best adsorbents obtained showed the lowest height of the mass transfer zone and one of the highest amounts adsorbed at the breakthrough point, either per mass or volume unit. However, it had a lower elastic modulus and compressive strength than other monolithic carbon aerogels, although its compressive strength (3 MPa) was still high enough to use it in carbon bed columns. The sample with the best mechanical properties was a poorer adsorbent. Regeneration of the exhausted adsorbents allowed the recovery of the hydrocarbons adsorbed without any appreciable loss of adsorption capacity of the carbon bed. PMID- 17722943 TI - Fingerprinting species and strains of Bacilli spores by distinctive coat surface morphology. AB - In this work, we applied high-resolution atomic force microscopy (AFM) to identify and characterize similarities and differences in the spore surface morphology of strains from four species of Bacilli: B. anthracis, B. cereus, B. pumilis, and B. subtilis. Common features of the examined spores in the dry state included ridges that spanned the long axis of each spore, and nanometer-scale fine rodlets that covered the entire spore surface. However, important differences in these features between species permitted them to be distinguished by AFM. Specifically, each species possessed significant variation in ridge architecture, and the rodlet width in B. anthracis was significantly less than that of the other species. To characterize similarities and differences within a species, we examined three B. subtilis strains. The ridge patterns among the three strains were largely the same; however, we detected significant differences in the ridge dimensions. Taken together, these experiments provide important information about natural variation in spore surface morphology, define structural features that can serve as species- and strain-specific signatures, and give insight into the dynamics of spore coat flexibility and its role during spore dormancy and germination. PMID- 17722944 TI - Strain and shape of epitaxial InAs/InP nanowire superlattice measured by grazing incidence X-ray techniques. AB - Quantitative structural information about epitaxial arrays of nanowires are reported for a InAs/InP longitudinal heterostructure grown by chemical beam epitaxy on an InAs (111)B substrate. Grazing incidence X-ray diffraction allows the separation of the nanowire contribution from the substrate overgrowth and gives averaged information about crystallographic phases, epitaxial relationships (with orientation distribution), and strain. In-plane strain inhomogeneities, intrinsic to the nanowires geometry, are measured and compared to atomistic simulations. Small-angle X-ray scattering evidences the hexagonal symmetry of the nanowire cross-section and provides a rough estimate of size fluctuations. PMID- 17722945 TI - GaAs/AlGaAs nanowire heterostructures studied by scanning tunneling microscopy. AB - We directly image the interior of GaAs/AlGaAs axial and radial nanowire heterostructures with atomic-scale resolution using scanning tunneling microscopy. We show that formation of monolayer sharp and smooth axial interfaces are possible even by vapor-phase epitaxy. However, we also find that instability of the ternary alloys formed in the Au seed fundamentally limits axial heterostructure control, inducing large segment asymmetries. We study radial core shell nanowires, imaging even ultrathin submonolayer shells. We demonstrate how large twinning-induced morphological defects at the wire surfaces can be removed, ensuring the formation of wires with atomically flat sides. PMID- 17722946 TI - Colloidal quantum dots in all-dielectric high-Q pillar microcavities. AB - We have fabricated all-dielectric high-Q optical pillar resonators with embedded colloidal CdSe/ZnS quantum dots or rods as light emitters by focused ion beam milling. Three-dimensional light confinement and distinct pillar microcavity modes are observed. Results from a waveguide model for the mode patterns and their spectral positions are in excellent agreement with the experimental data. Cavities with elliptical cross sections show higher quality factors in the short axis direction than do circular resonators of the same cross-sectional area. PMID- 17722948 TI - Regulation of cerebral blood flow during exercise. AB - Constant cerebral blood flow (CBF) is vital to human survival. Originally thought to receive steady blood flow, the brain has shown to experience increases in blood flow during exercise. Although increases have not consistently been documented, the overwhelming evidence supporting an increase may be a result of an increase in brain metabolism. While an increase in metabolism may be the underlying causative factor for the increase in CBF during exercise, there are many modulating variables. Arterial blood gas tensions, most specifically the partial pressure of carbon dioxide, strongly regulate CBF by affecting cerebral vessel diameter through changes in pH, while carbon dioxide reactivity increases from rest to exercise. Muscle mechanoreceptors may contribute to the initial increase in CBF at the onset of exercise, after which exercise-induced hyperventilation tends to decrease flow by pial vessel vasoconstriction. Although elite athletes may benefit from hyperoxia during intense exercise, cerebral tissue is well protected during exercise, and cerebral oxygenation does not appear to pose a limiting factor to exercise performance. The role of arterial blood pressure is important to the increase in CBF during exercise; however, during times of acute hypotension such as during diastole at high-intensity exercise or post-exercise hypotension, cerebral autoregulation may be impaired. The impairment of an increase in cardiac output during exercise with a large muscle mass similarly impairs the increase in CBF velocity, suggesting that cardiac output may play a key role in the CBF response to exercise. Glucose uptake and CBF do not appear to be related; however, there is growing evidence to suggest that lactate is used as a substrate when glucose levels are low. Traditionally thought to have no influence, neural innervation appears to be a protective mechanism to large increases in cardiac output. Changes in middle cerebral arterial velocity are independent of changes in muscle sympathetic nerve activity, suggesting that sympathetic activity does not alter medium-sized arteries (middle cerebral artery).CBF does not remain steady, as seen by apparent increases during exercise, which is accomplished by a multi-factorial system, operating in a way that does not pose any clear danger to cerebral tissue during exercise under normal circumstances. PMID- 17722949 TI - Future perspectives in the evaluation of the physiological demands of soccer. AB - Soccer (association football) is a team sport that incorporates frequent fluctuations between high and low exercise intensities. These unpredictable changes may be accompanied by unorthodox patterns of movements and the performance of specific skills. The individual activity profiles are highly variable and include elements of self-pacing, since decision making about opportunities to become engaged in play dictates individual activities. Approaches utilised to investigate the demands placed on players during competitive performances include behavioural observations during games, physiological evaluations in matches and assessments of the physical capacity of players. Observations made during games to determine the work-rate patterns of individual players are highly variable and make generalisations based on individual activity patterns conditional, unless the sample sizes are large and data are collected on a number of occasions. The data may also be affected by the diverse methodological approaches to their collection and analysis and a failure to determine the reliability and objectivity of the relevant measuring tools. Techniques that can be used to collect data in matches are limited as the sports rules and regulations restrict some approaches. The validity of applying data from non-competitive matches to the competitive situation must, therefore, be subject to formal scrutiny. There is also a concern as to the degree to which principles of steady-state are applicable to dynamically changing exercise intensities. In the evaluation of the physical capacities of players, the variability in overall soccer performance is reduced to fitness statistics, whereas in reality, soccer performance is a construct based on many different performance components and their interaction at the level of both player and team. Despite these caveats, valuable insights have been acquired into the physiological requirements of the game that have subsequently informed both research projects and impacted upon practice. The challenge for future researchers is to overcome remaining research design hurdles and devise ways to understand more fully the complexities of invasive field games such as soccer. The interactions between individuals within a team require investigation and there is a need to refine and develop methods that employ sophisticated measurement techniques and yet possess both internal and external validity, such as laboratory-based simulations. PMID- 17722950 TI - Altering the length-tension relationship with eccentric exercise : implications for performance and injury. AB - The effects of eccentric exercise on muscle injury prevention and athletic performance are emerging areas of interest to researchers. Of particular interest are the adaptations that occur after a single bout, or multiple bouts of eccentric exercise. It has been established that after certain types of eccentric exercise, the optimum length of tension development in muscle can be shifted to longer muscle lengths. Altering the length-tension relationship can have a profound influence on human movements. It is thought that the length-tension relationship is influenced by the structural makeup of muscle. However, the mechanism responsible for the shift in optimum length is not readily agreed upon. Despite the conflict, several studies have reported a shift in optimum length after eccentric exercise. Unfortunately, very few of these studies have been randomised, controlled training studies, and the duration of the shift has not yet been established. Nonetheless, this adaptation may result in greater structural stability at longer muscle lengths and consequently may have interesting implications for injury prevention and athletic performance. Both contentions remain relatively unexplored and provide the focus of this review. PMID- 17722947 TI - The molecular bases of training adaptation. AB - Skeletal muscle is a malleable tissue capable of altering the type and amount of protein in response to disruptions to cellular homeostasis. The process of exercise-induced adaptation in skeletal muscle involves a multitude of signalling mechanisms initiating replication of specific DNA genetic sequences, enabling subsequent translation of the genetic message and ultimately generating a series of amino acids that form new proteins. The functional consequences of these adaptations are determined by training volume, intensity and frequency, and the half-life of the protein. Moreover, many features of the training adaptation are specific to the type of stimulus, such as the mode of exercise. Prolonged endurance training elicits a variety of metabolic and morphological changes, including mitochondrial biogenesis, fast-to-slow fibre-type transformation and substrate metabolism. In contrast, heavy resistance exercise stimulates synthesis of contractile proteins responsible for muscle hypertrophy and increases in maximal contractile force output. Concomitant with the vastly different functional outcomes induced by these diverse exercise modes, the genetic and molecular mechanisms of adaptation are distinct. With recent advances in technology, it is now possible to study the effects of various training interventions on a variety of signalling proteins and early-response genes in skeletal muscle. Although it cannot presently be claimed that such scientific endeavours have influenced the training practices of elite athletes, these new and exciting technologies have provided insight into how current training techniques result in specific muscular adaptations, and may ultimately provide clues for future and novel training methodologies. Greater knowledge of the mechanisms and interaction of exercise-induced adaptive pathways in skeletal muscle is important for our understanding of the aetiology of disease, maintenance of metabolic and functional capacity with aging, and training for athletic performance. This article highlights the effects of exercise on molecular and genetic mechanisms of training adaptation in skeletal muscle. PMID- 17722951 TI - Changing epidemiology of rare mould infections: implications for therapy. AB - There has been an increase in rare mould infections in recent decades. These infections have been reported primarily in severely immunocompromised patients. The emergence of these organisms is multifactorial and can be related to more intense immunosuppression, the prolonged survival of patients who have what were previously fatal diseases, and the selective pressure of broad spectrum antifungal agents used for prophylaxis or therapy. Among these rare mould infections, the Zygomycetes are the most commonly encountered, and in some institutions the increase in these organisms appears to be associated with the use of voriconazole. Aspergillus terreus, a species that is resistant to amphotericin B, and less frequently, A. ustus and A. lentulus, have been noted increasingly as causes of invasive aspergillosis in tertiary care centres in the US. Several species of Scedosporium with innate resistance to many antifungal agents have emerged as major causes of disseminated mould infections that are frequently very difficult to treat. Among patients who have haematological malignancies, are neutropenic or have received a haematopoietic stem cell transplant, infections due to Fusarium species respond poorly to many antifungal agents. Dematiaceous, or brown-black, fungi, most often associated with chronic localised infections, are now increasingly reported as a cause of disseminated infection in immunosuppressed hosts. Concomitant with the increased number of infections with these rare moulds, several new mould-active antifungal agents have been developed. The new expanded spectrum azole, voriconazole, has changed our approach to moulds such as S.apiospermum, Fusarium species and A. terreus that are amphotericin B resistant. Posaconazole, the most recently approved expanded spectrum azole, is the first drug in the azole class to show activity against the Zygomycetes and has proven extremely useful for step-down therapy after initial treatment with amphotericin B. It is not known whether posaconazole is effective as primary therapy for zygomycosis; the use of this agent for that purpose awaits clinical trials with the recently developed intravenous formulation of posaconazole. PMID- 17722952 TI - Insulin therapy in diabetes mellitus: how can the currently available injectable insulins be most prudently and efficaciously utilised? AB - The era of animal source insulins has passed and human recombinant DNA insulins are gradually being replaced because of the superior efficacy of insulin analogues. Analogue insulins are available in both rapid- and long-acting preparations. Currently available rapid-acting insulins are lispro, aspart and glulisine, and the currently available long-acting analogue basal insulins are detemir and glargine. The rapid-acting insulin analogues are also available in combination with protamine in fixed-dose pre-mixed insulins to provide a more sustained action. The chemical structure, subcutaneous behaviour, time of onset, maximal effect and duration of action of both analogue and human insulins, and how these actions can be best utilised in the diabetic patient are discussed in this review. In addition, strategies where efficacy of the available analogue insulins can be maximally utilised in both type 1 and type 2 diabetes mellitus are described. Maximal utilisation of analogue insulins will result not only in better glycaemic control, but will also minimise the frequency and severity of hypoglycaemic episodes. In addition, maximisation of glycaemic control will result in prevention, delay of onset or amelioration of both the microvascular and perhaps the macrovascular complications of diabetes. PMID- 17722954 TI - Metastatic colorectal cancer: current systemic treatment options. AB - The treatment of colorectal cancer has become increasingly complex over recent years. With the emergence of new chemotherapy drugs and targeted agents, there has been great improvement in the prognosis of patients with metastatic colorectal cancer. This review summarises the evidence supporting the use of combination chemotherapy with oxaliplatin and/or irinotecan with fluorouracil (5 FU) for the treatment of colorectal cancer and outlines the pivotal trials. Phase III trials have demonstrated the superiority of combination chemotherapy over single-agent 5-FU, but the optimal sequencing and combination of treatment is yet to be determined. Oral fluoropyrimidine derivatives have been shown to be equivalent to bolus 5-FU treatment and these offer another option for the treatment of colorectal cancer, but further studies are required to evaluate their use with irinotecan and oxaliplatin. The use of newer targeted therapies, such as bevacizumab and cetuximab, alone and in combination with chemotherapy are discussed, and the most recent data supporting their use is outlined. Bevacizumab containing regimens have been shown to be superior to those without for the first line treatment of colorectal cancer, and cetuximab has demonstrated activity in combination with chemotherapy in both the first- and second-line setting. Other targeted agents, such as vatalanib and panitumumab, are discussed and early clinical studies with these agents show promising results. PMID- 17722955 TI - Lenalidomide in myelodysplastic syndrome and multiple myeloma. AB - The use of thalidomide is limited by adverse effects of sedation, constipation, neuropathy and thromboembolism. In order to discover more potent and less toxic immunomodulators than thalidomide, its chemical structure was modified and lenalidomide was formed. Lenalidomide is approved by the US FDA for the treatment of patients with low-risk myelodysplastic syndrome (MDS) with deletion 5q cytogenetic abnormality. Two studies and a case report have evaluated lenalidomide in these MDS patients and showed significantly higher cytogenetic responses and durable red blood cell transfusion independence. Lenalidomide should be the drug of choice for patients with low and intermediate-1 risk MDS (based on the International Prognostic Scoring System) with chromosome 5q31 deletion with or without other karyotype abnormalities. Lenalidomide, in combination with dexamethasone, has been compared with dexamethasone alone in patients with relapsed or refractory multiple myeloma (MM) in two studies (MM-009 in North America and MM-010 in Europe, Israel and Australia). In these two phase III trials, lenalidomide demonstrated impressive (58-59%) response rates with dexamethasone. Lenalidomide has also been shown to overcome thalidomide resistance in MM patients. Therefore, the lenalidomide plus dexamethasone regimen provides another treatment option, in addition to first line MM treatment regimens of bortezomib, thalidomide or high-dose dexamethasone, for the treatment of relapsed or refractory MM. Lenalidomide does not produce significant sedation, constipation or neuropathy, but does lead to significant myelosuppression, unlike thalidomide. The prescribing information has a black box warning for risk of myelosuppression, deep vein thrombosis/pulmonary embolism and teratogenicity. Administration of lenalidomide is recommended at a starting dose of 10 mg/day orally for deletion 5q in MDS patients. Significant risk of myelosuppression may lead to dose reduction in the majority of these patients. Clinical trials of relapsed and refractory MM have shown that lenalidomide is clinically efficacious at a dosage of 25 mg/day when administered in combination with dexamethasone. Lenalidomide should be continued until disease progression in both MDS and MM patients. PMID- 17722953 TI - Ampicillin/sulbactam: current status in severe bacterial infections. AB - Ampicillin/sulbactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity against Gram-positive, Gram-negative and anaerobic bacteria. Data from comparative studies justify the use of ampicillin/sulbactam in a 2 : 1 ratio in various severe bacterial infections. In comparative clinical trials, ampicillin/sulbactam has proved to be a significant drug in the therapeutic armamentarium for lower respiratory tract infections and aspiration pneumonia, gynaecological/obstetrical infections, intra-abdominal infections, paediatric infections such as acute epiglottitis and periorbital cellulitis, diabetic foot infections, and skin and soft tissue infections. Of particular interest during this era of increasing antimicrobial resistance in various settings and populations is the effectiveness of sulbactam against a considerable proportion of infections due to Acinetobacter baumannii. PMID- 17722957 TI - Docetaxel: in gastric cancer. AB - Docetaxel is a taxane analogue that inhibits microtubule disassembly and, in cultured gastric cancer cells, induces apoptosis-associated binding activity of the transcription factor activating protein-1, and activates the proapoptotic genes BCL2L1 and BAX. In patients with metastatic or locally advanced/recurrent gastric or gastro-oesophageal junction adenocarcinoma, the median time to tumour progression was significantly prolonged with 3-week cycles of intravenous (IV) docetaxel plus cisplatin and fluorouracil (5-fluorouracil) compared with 4-week cycles of IV cisplatin plus IV fluorouracil (5.6 vs 3.7 months) in a large (n = 445), randomised, multicentre, phase III trial. Furthermore, recipients of this triple regimen experienced a significantly longer median overall survival time, a higher overall response rate and delayed deterioration in health-related quality of life than those receiving cisplatin plus fluorouracil. These data are supported by two large (n > 100), randomised, phase II studies in patients with metastatic or locally advanced/recurrent gastric or gastro-oesophageal junction cancer. In general, combination therapy with docetaxel, cisplatin and fluorouracil was relatively well tolerated given the nature of chemotherapy in patients with metastatic or locally advanced/recurrent gastric or gastro oesophageal adenocarcinoma PMID- 17722958 TI - Docetaxel in gastric cancer: a viewpoint by David Wilson. PMID- 17722959 TI - Docetaxel in gastric cancer: a viewpoint by Andre M. Murad. PMID- 17722956 TI - Primary ciliary dyskinesia: recent advances in pathogenesis, diagnosis and treatment. AB - Primary ciliary dyskinesia is a genetic disorder causing dysfunctional motility of cilia and impaired mucociliary clearance, resulting in a myriad of clinical manifestations including recurrent sinopulmonary disease, laterality defects and infertility. The heterogenous clinical presentation of primary ciliary dyskinesia and the limitations of transmission electron microscopy to assess ultrastructural defects within the cilium often delay diagnosis. Recent advances in the understanding of the basic biology and function of the cilium have led to potential diagnostic alternatives, including ciliary beat analysis and nasal nitric oxide measurements. Moreover, the identification of disease-causing mutations could lead to the development of comprehensive genetic testing that may overcome many of the current diagnostic limitations. Although the clinical manifestations of primary ciliary dyskinesia have been recognised for over a century, there are few studies examining treatments and standards of care have yet to be established. Multicentre collaborative efforts have been established in North America and Europe, which should help to develop standardised approaches to the diagnosis and treatment of primary ciliary dyskinesia. PMID- 17722960 TI - Fluticasone furoate: intranasal use in allergic rhinitis. AB - Fluticasone furoate nasal spray is a new topical intranasal corticosteroid with enhanced affinity for the glucocorticoid receptor and low systemic exposure, which was recently approved in the US for the treatment of seasonal or perennial allergic rhinitis in adults and in children aged >or=2 years. Fluticasone furoate nasal spray employs a novel delivery device with a unique side-actuated design, a short nozzle and a new trigger mechanism designed for ease of use. In well controlled clinical trials, intranasal fluticasone furoate 110microg once daily for 2 weeks in adults and adolescents with seasonal allergic rhinitis reduced nasal and ocular symptoms, and improved health-related quality of life to a significantly greater extent than placebo. Similarly, treatment with intranasal fluticasone furoate 110microg once daily for 4-6 weeks in adults and adolescents with perennial allergic rhinitis was superior to placebo in reducing nasal symptoms and with respect to overall response to therapy. In children aged 6-11 years, fluticasone furoate nasal spray was shown to be effective in reducing the nasal symptoms of seasonal and perennial allergic rhinitis following treatment for 2 and 4 weeks, respectively. Fluticasone furoate nasal spray was well tolerated in adults, adolescents and children aged 2-11 years, with an overall incidence of adverse events similar to that with placebo. PMID- 17722963 TI - Tacrolimus once-daily formulation in the prophylaxis of transplant rejection in renal or liver allograft recipients: a viewpoint by Helio Tedesco Silva Jr. PMID- 17722962 TI - Tacrolimus once-daily formulation: in the prophylaxis of transplant rejection in renal or liver allograft recipients. AB - Tacrolimus once-daily (OD) is a new oral formulation of the well established immunosuppressant tacrolimus. Tacrolimus OD provided equivalent steady-state systemic tacrolimus exposure to that achieved with standard oral tacrolimus twice daily in stable renal and liver transplant recipients. The two formulations also provided broadly similar steady-state systemic exposure in de novo renal and liver transplant recipients. In a large, randomised, nonblind, multicentre, three armed, noninferiority trial in de novo renal transplant recipients, the efficacy failure rates (primary endpoint) [any patient who died, experienced graft failure, had a biopsy-confirmed acute rejection or was lost to follow-up] of tacrolimus OD (14.0%) and standard tacrolimus (15.1%) were noninferior to that of ciclosporin (cyclosporine) microemulsion (17.0%) at 1 year, when each was given in conjunction with corticosteroids, mycophenolate mofetil and basiliximab induction. Data from a pharmacokinetic study suggests that tacrolimus OD has similar efficacy to standard tacrolimus in de novo liver transplant recipients over 6 weeks of treatment. In noncomparative 2-year trials, tacrolimus OD was effective in stable renal and liver transplant recipients converted to tacrolimus OD from standard tacrolimus. The overall tolerability profile of tacrolimus OD appears to be similar to that of standard tacrolimus in de novo and stable renal and liver transplant patients. PMID- 17722961 TI - Telbivudine. AB - Telbivudine, the unmodified L-enantiomer of the naturally occurring nucleoside D thymidine, is a potent synthetic nucleoside analogue. It acts as a hepatitis B virus (HBV) polymerase inhibitor and preferentially inhibits HBV second strand (DNA-dependent) compared with first strand (RNA-dependent) DNA synthesis. More telbivudine than lamivudine recipients with hepatitis B e antigen (HBeAg) positive chronic hepatitis B and similar proportions of telbivudine or lamivudine recipients with HBeAg-negative disease achieved a therapeutic response at 52 weeks in the large 2-year GLOBE trial. In a phase III trial in Chinese patients, greater reductions in serum HBV DNA occurred with telbivudine than lamivudine at 52 weeks. Reductions in serum HBV DNA at 24 weeks were greater with telbivudine than adefovir in the 1-year switching trial. A lower residual viral load at 52 weeks was seen in patients who received telbivudine or who switched from adefovir to telbivudine at 24 weeks than in patients receiving adefovir. In the 1-year lamivudine switching trial in patients with serum HBV DNA levels >3 log10 copies/mL despite having received prior treatment with lamivudine for a mean of [almost equal or equal to]7 months, those randomised to telbivudine therapy achieved greater reductions in serum HBV DNA levels at 24 weeks than patients randomised to continue lamivudine therapy. Telbivudine was generally well tolerated and most adverse events were of mild or moderate severity. The incidence of severe ALT flares with telbivudine was half that seen with lamivudine at both 52 and 104 weeks in the GLOBE trial. PMID- 17722964 TI - Tacrolimus once-daily formulation in the prophylaxis of transplant rejection in renal or liver allograft recipients: a viewpoint by Sander Florman. PMID- 17722965 TI - Nitazoxanide: a review of its use in the treatment of gastrointestinal infections. AB - Nitazoxanide (Alinia, Daxon, Dexidex, Paramix, Kidonax, Colufase, Annita) has in vitro activity against a variety of microorganisms, including a broad range of protozoa and helminths. Nitazoxanide is effective in the treatment of protozoal and helminthic infections, including Cryptosporidium parvum or Giardia lamblia, in immunocompetent adults and children, and is generally well tolerated. Nitazoxanide is a first-line choice for the treatment of illness caused by C. parvum or G. lamblia infection in immunocompetent adults and children, and is an option to be considered in the treatment of illnesses caused by other protozoa and/or helminths. PMID- 17722966 TI - Is there still a role for aprotinin in cardiac surgery? AB - Cardiac surgery is associated with a systemic inflammatory response and systemic coagulopathy, which can result in significant organ dysfunction and bleeding. Aprotinin, a serine protease inhibitor, can limit systemic inflammation, and has been associated with myocardial, pulmonary and cerebral protection in addition to its proven haemostatic efficacy. Data are currently conflicting regarding the haemostatic efficacy of aprotinin relative to alternative agents including tranexamic acid. Recent studies have demonstrated aprotinin usage is associated with increased rates of thrombotic and renal complications, but these findings are at odds with the majority of studies relating to aprotinin safety to date. The lack of adequately powered, randomised studies evaluating aprotinin and alternative agents limits drawing conclusions about the complete use or disuse of aprotinin presently and requires individualised patient selection based on bleeding risk and co-morbidities for its usage. PMID- 17722967 TI - Thiazolidinediones and their fluid-related adverse effects: facts, fiction and putative management strategies. AB - Thiazolidinediones (TZDs) or glitazones are agents that are widely used for the treatment of type 2 diabetes mellitus. These drugs have a multitude of therapeutic effects including reduction in insulin resistance and hyperglycaemia, anti-inflammatory effects and amelioration of hypertension, microalbuminuria and hepatic steatosis. The TZD molecular target, peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear transcription factor, is expressed diffusely in humans, including many tissues comprising the cardiovascular and renal systems. This suggests a potential for TZDs to elicit perturbing effects on these systems, which are independent of their effects on glucose and lipid metabolism. One of the most common adverse effects of TZDs is fluid retention, which can result in, or exacerbate, oedema and congestive heart failure (CHF). The frequency of peripheral oedema is approximately 5% when TZDs are used in mono or combination oral therapy, and about 15% when used with insulin. Patients with type 2 diabetes are at high risk of myriad morbid complications, including CHF. The development of CHF, particularly in the elderly, is a harbinger of premature mortality. TZD-induced oedema is largely peripheral, may have its origins in changes in haemodynamics, with some contribution from molecules, which regulate cell and tissue permeability (e.g. vascular endothelial growth factor and protein kinase Cbeta), and remains the preponderant manifestation of TZD-induced fluid retention even in those with existing heart failure. Preclinical and pilot clinical data attest to the fact that at least part of the fluid retention derives from a direct effect of TZDs on sodium reabsorption via the renal medullary collecting duct, a mechanism that is sensitive to diuretic agents that have this nephron segment as their site of action, in whole or in part (spironolactone, amiloride and hydrochlorothiazide). Our review suggests various potential clinical strategies by which TZD-induced fluid retention might be effectively monitored and addressed. PMID- 17722968 TI - Safety considerations with bisphosphonates for the treatment of osteoporosis. AB - Bisphosphonates are the most commonly prescribed medications for the treatment of osteoporosis. Although evidence supports a good safety profile for these agents, numerous tolerability issues have been associated with their use. This review provides an overview of the safety issues associated with the nitrogen-containing class of bisphosphonates and discusses the potential effect of these issues on adherence. The review specifically considers upper gastrointestinal (UGI) adverse events (AEs), renal toxicity, influenza-like illness, osteonecrosis of the jaw and evidence on how to treat or prevent these events. In clinical trials, UGI AEs, including severe events such as oesophageal ulcer, oesophagitis and erosive oesophagitis, have been reported at similar frequencies in placebo- and active treatment arms. However, postmarketing studies have highlighted UGI AEs as a concern. These studies show that a significant portion of patients are less compliant with administration instructions outside strict clinical trial supervision, and when oral bisphosphonates are not administered as directed, patients are more likely to experience UGI AEs. Some clinical trials with oral bisphosphonates have suggested that a decrease in the frequency of administration may lead to improvement in gastrointestinal tolerability. In the authors' experience, the issue of UGI tolerability can be minimised by explaining to the patient and/or caregiver the importance of following administration instructions. Intravenous (IV) bisphosphonates have been recently approved for use in osteoporosis, offering an alternative regimen for patients with osteoporosis. Earlier generation IV bisphosphonates (e.g. etidronate) have been associated with acute renal failure. Alternatively, late-generation IV bisphosphonates (i.e. ibandronate) have shown a better safety profile in relation to renal toxicity. Influenza-like illness, often referred to as an acute-phase reaction, covers symptoms such as fatigue, fever, chills, myalgia and arthralgia. These symptoms are transitory and self-limiting and usually do not recur after subsequent drug administration. Symptoms of influenza-like illness have been associated with both IV and oral bisphosphonates. Osteonecrosis of the jaw has also been associated with IV bisphosphonate treatment, particularly in patients treated with high doses. A small number of patients with cancer and osteoporosis using oral bisphosphonates have also reported this AE. As osteonecrosis of the jaw is difficult to treat and is often associated with dental procedures and poor oral hygiene, preventive measures seem to be the best management option for patients taking bisphosphonates.Overall, the safety and tolerability profile of the nitrogen-containing bisphosphonates is good, and long-term treatment does not appear to carry a risk of serious AEs. By encouraging adherence to administration instructions physicians can minimise certain complications, such as UGI intolerability. By being aware of other potential safety issues, such as renal impairment, influenza-like illness and osteonecrosis of the jaw, physicians can detect these AEs early in the course of treatment. PMID- 17722969 TI - Benefit-risk assessment of nesiritide in the treatment of acute decompensated heart failure. AB - Nesiritide is a recombinant form of human B-type natriuretic peptide, a naturally occurring endogenous hormone released by cardiac ventricles in response to an increase in ventricular wall stress. Its use in the treatment of acute decompensated heart failure (ADHF) has been evaluated in a series of randomised controlled clinical trials. It is currently approved in the US for the treatment of ADHF. Nesiritide induces a balanced vasodilation and an indirect increase in cardiac output, but has no actual inotropic effects and exerts a neutral effect on heart rate. In addition, it inhibits adverse neurohormonal activation and, in some individuals, promotes natriuresis and diuresis. In adults with ADHF, nesiritide reduces pulmonary capillary wedge pressure, right atrial pressure and systemic vascular resistance; decreases symptoms of heart failure; and enhances global clinical status. Important questions regarding the risks of nesiritide therapy have recently been raised, and resolution of the safety of nesiritide is a process that remains in evolution. The most frequently reported adverse effect is dose-related hypotension. In addition, nesiritide may cause an acute increase in serum creatinine concentration. This increase seems to be a haemodynamic response to a combination of volume depletion, vasodilation and neurohormonal inhibition. Nesiritide-induced changes in renal function have not been definitively shown to negatively affect mortality. The effect of nesiritide on all-cause mortality is currently unresolved. Recent meta-analyses of existing databases have raised concerns regarding adverse effects of the drug on 30-day mortality. However, reviews of large, observational, registry databases do not suggest an adverse inpatient mortality effect compared with other vasodilator therapies. Further resolution of the mortality question awaits completion of pending randomised controlled clinical trials. When used for approved indications and according to recommended dosage and administration regimens, nesiritide represents a reasonable treatment adjunct for ADHF. PMID- 17722972 TI - Adverse drug event detection in a community hospital utilising computerised medication and laboratory data. AB - OBJECTIVE: Computerised monitors can detect and, with clinical intervention, often prevent or ameliorate adverse drug events (ADEs). We evaluated whether a computer-based alerting system was useful in a community hospital setting. METHODS: We evaluated 6 months of retrospectively collected medication and laboratory data from a 140-bed community hospital, and applied the rules from a computerised knowledge base to determine if the resulting alerts might have allowed a clinician to prevent or lessen harm related to medication toxicity. We randomly selected 11% (n = 58, of which 56 were available) of charts deemed to be high- or critical-priority alerts, based on the likelihood of the alerts being associated with injury, to determine the frequencies of ADEs and preventable ADEs. RESULTS: In 6 months, there were 8829 activations of the rule set, generating a total of 3547 alerts. Of these, 528 were of high or critical priority, 664 were of medium priority and 2355 were of low priority. Chart review among the sample (56 charts) of high- or critical-priority alerts found five non preventable and two preventable ADEs, suggesting that among the total high- or critical-priority alerts alone, there would be approximately 94 non-preventable ADEs and 37 preventable ADEs annually in this hospital that could be detected using this method. CONCLUSIONS: Computer-based rules engines have the potential to identify and, with clinical intervention, mitigate preventable ADEs, and implementation is feasible in community hospitals without an advanced information technology application. PMID- 17722971 TI - Clinical pattern of zileuton-associated liver injury: results of a 12-month study in patients with chronic asthma. AB - OBJECTIVE: Zileuton is a 5-lipoxygenase inhibitor approved by the US FDA in 1996 for the treatment of asthma in adults and children. During phase II/III clinical trials, zileuton was generally well tolerated, although elevations in ALT and AST levels were noted in some patients, and a single treated patient developed hepatocellular jaundice. To more fully characterise the hepatic effects of zileuton, and to establish appropriate monitoring guidelines, a 12-month open label, safety surveillance study was conducted prior to FDA approval. PATIENTS AND METHODS: In this study, 2458 patients with asthma received zileuton 600mg four times daily in addition to usual asthma care, and 489 patients were treated with usual asthma care only. All patients had their liver biochemistry checked monthly for the first 5 months, and at months 7, 10 and 12 thereafter. RESULTS: A total of 109 patients (4.4%) receiving zileuton treatment had elevations in ALT levels to > or =3 x the upper limit of normal (ULN), including 31 patients (1.3%) who had levels elevated to > or =8 x ULN, compared with 5 of 480 patients in the usual care alone group (1.0%) who had levels elevated to > or =3 x ULN, of whom 1 (0.2%) had levels elevated to > or =8 x ULN. Elevations in ALT levels were generally not associated with increases in alkaline phosphatase and/or total bilirubin levels. Therefore, the hepatic injury was predominantly hepatocellular. The majority of elevations in ALT level to > or =3 x ULN (64.2%) in the zileuton treated group occurred within the first 3 months of treatment. There was no correlation between the time of onset of ALT level elevation and the height of the peak ALT level observed. There was no overall difference in the occurrence of elevations in ALT level to > or =3 x ULN between men (4.5%) and women (4.7%), but more women than men experienced an ALT level > or =8 x ULN (1.8% vs 0.5%). Women aged > or =65 years appeared to be at higher risk of elevated ALT levels than those aged <65 years (a rate of 10.1% compared with 4.1%). Patients who experienced ALT levels of > or =3 x ULN but <5 x ULN were allowed to remain on treatment and 52.5% of these patients were able to continue zileuton therapy and experienced resolution of the elevation (a reduction in level to <2 x ULN). In each of the patients who discontinued treatment because of elevated ALT levels, the ALT level returned towards baseline, with a mean time to resolution (defined as a reduction in levels to <2 x ULN) of 4 weeks. No patient in this study developed clinically apparent jaundice or liver failure. Two patients (0.1%) experienced total bilirubin levels > or =1.5 x ULN in association with serum ALT levels exceeding 3 x ULN. CONCLUSIONS: This study established that liver chemistry monitoring is most effective in detecting elevation of ALT levels during the first 3 months of zileuton therapy and that with appropriate monitoring the risk of irreversible liver injury appears to be low. PMID- 17722970 TI - Drug-induced cardiovascular disorders. AB - As the variety and range of pharmaceutical agents available to the medical profession continues to expand, one unavoidable effect will be an increase in drug-induced disease, including cardiovascular disorders. However, given the high rates of cardiovascular disease and prevalence of recognised cardiovascular risk factors in the population, it is sometimes impossible to conclusively attribute any individual patients' ill health to one particular drug. As a result, the relationship between drugs and cardiovascular disease is often difficult to quantify. This review discusses specific forms of drug-induced cardiovascular disease such as heart failure, left ventricular systolic dysfunction, hypertension and arrhythmia. Suspected culprit drugs for all disorders are highlighted. Specific attention is given to certain drug groups with a strong association with one or more forms of cardiovascular disease: these include anthracyclines, antipsychotics, NSAIDs and cyclo-oxygenase 2 inhibitors. Additionally, advice is offered on how physicians might distinguish drug-induced cardiovascular disorders from other aetiologies. PMID- 17722973 TI - Inferring function using patterns of native disorder in proteins. AB - Natively unstructured regions are a common feature of eukaryotic proteomes. Between 30% and 60% of proteins are predicted to contain long stretches of disordered residues, and not only have many of these regions been confirmed experimentally, but they have also been found to be essential for protein function. In this study, we directly address the potential contribution of protein disorder in predicting protein function using standard Gene Ontology (GO) categories. Initially we analyse the occurrence of protein disorder in the human proteome and report ontology categories that are enriched in disordered proteins. Pattern analysis of the distributions of disordered regions in human sequences demonstrated that the functions of intrinsically disordered proteins are both length- and position-dependent. These dependencies were then encoded in feature vectors to quantify the contribution of disorder in human protein function prediction using Support Vector Machine classifiers. The prediction accuracies of 26 GO categories relating to signalling and molecular recognition are improved using the disorder features. The most significant improvements were observed for kinase, phosphorylation, growth factor, and helicase categories. Furthermore, we provide predicted GO term assignments using these classifiers for a set of unannotated and orphan human proteins. In this study, the importance of capturing protein disorder information and its value in function prediction is demonstrated. The GO category classifiers generated can be used to provide more reliable predictions and further insights into the behaviour of orphan and unannotated proteins. PMID- 17722974 TI - A logical model provides insights into T cell receptor signaling. AB - Cellular decisions are determined by complex molecular interaction networks. Large-scale signaling networks are currently being reconstructed, but the kinetic parameters and quantitative data that would allow for dynamic modeling are still scarce. Therefore, computational studies based upon the structure of these networks are of great interest. Here, a methodology relying on a logical formalism is applied to the functional analysis of the complex signaling network governing the activation of T cells via the T cell receptor, the CD4/CD8 co receptors, and the accessory signaling receptor CD28. Our large-scale Boolean model, which comprises 94 nodes and 123 interactions and is based upon well established qualitative knowledge from primary T cells, reveals important structural features (e.g., feedback loops and network-wide dependencies) and recapitulates the global behavior of this network for an array of published data on T cell activation in wild-type and knock-out conditions. More importantly, the model predicted unexpected signaling events after antibody-mediated perturbation of CD28 and after genetic knockout of the kinase Fyn that were subsequently experimentally validated. Finally, we show that the logical model reveals key elements and potential failure modes in network functioning and provides candidates for missing links. In summary, our large-scale logical model for T cell activation proved to be a promising in silico tool, and it inspires immunologists to ask new questions. We think that it holds valuable potential in foreseeing the effects of drugs and network modifications. PMID- 17722975 TI - Design of multi-specificity in protein interfaces. AB - Interactions in protein networks may place constraints on protein interface sequences to maintain correct and avoid unwanted interactions. Here we describe a "multi-constraint" protein design protocol to predict sequences optimized for multiple criteria, such as maintaining sets of interactions, and apply it to characterize the mechanism and extent to which 20 multi-specific proteins are constrained by binding to multiple partners. We find that multi-specific binding is accommodated by at least two distinct patterns. In the simplest case, all partners share key interactions, and sequences optimized for binding to either single or multiple partners recover only a subset of native amino acid residues as optimal. More interestingly, for signaling interfaces functioning as network "hubs," we identify a different, "multi-faceted" mode, where each binding partner prefers its own subset of wild-type residues within the promiscuous binding site. Here, integration of preferences across all partners results in sequences much more "native-like" than seen in optimization for any single binding partner alone, suggesting these interfaces are substantially optimized for multi specificity. The two strategies make distinct predictions for interface evolution and design. Shared interfaces may be better small molecule targets, whereas multi faceted interactions may be more "designable" for altered specificity patterns. The computational methodology presented here is generalizable for examining how naturally occurring protein sequences have been selected to satisfy a variety of positive and negative constraints, as well as for rationally designing proteins to have desired patterns of altered specificity. PMID- 17722976 TI - Functional representation of enzymes by specific peptides. AB - Predicting the function of a protein from its sequence is a long-standing goal of bioinformatic research. While sequence similarity is the most popular tool used for this purpose, sequence motifs may also subserve this goal. Here we develop a motif-based method consisting of applying an unsupervised motif extraction algorithm (MEX) to all enzyme sequences, and filtering the results by the four level classification hierarchy of the Enzyme Commission (EC). The resulting motifs serve as specific peptides (SPs), appearing on single branches of the EC. In contrast to previous motif-based methods, the new method does not require any preprocessing by multiple sequence alignment, nor does it rely on over representation of motifs within EC branches. The SPs obtained comprise on average 8.4 +/- 4.5 amino acids, and specify the functions of 93% of all enzymes, which is much higher than the coverage of 63% provided by ProSite motifs. The SP classification thus compares favorably with previous function annotation methods and successfully demonstrates an added value in extreme cases where sequence similarity fails. Interestingly, SPs cover most of the annotated active and binding site amino acids, and occur in active-site neighboring 3-D pockets in a highly statistically significant manner. The latter are assumed to have strong biological relevance to the activity of the enzyme. Further filtering of SPs by biological functional annotations results in reduced small subsets of SPs that possess very large enzyme coverage. Overall, SPs both form a very useful tool for enzyme functional classification and bear responsibility for the catalytic biological function carried out by enzymes. PMID- 17722977 TI - V3 loop truncations in HIV-1 envelope impart resistance to coreceptor inhibitors and enhanced sensitivity to neutralizing antibodies. AB - The V1/V2 region and the V3 loop of the human immunodeficiency virus type I (HIV 1) envelope (Env) protein are targets for neutralizing antibodies and also play an important functional role, with the V3 loop largely determining whether a virus uses CCR5 (R5), CXCR4 (X4), or either coreceptor (R5X4) to infect cells. While the sequence of V3 is variable, its length is highly conserved. Structural studies indicate that V3 length may be important for interactions with the extracellular loops of the coreceptor. Consistent with this view, genetic truncation of the V3 loop is typically associated with loss of Env function. We removed approximately one-half of the V3 loop from three different HIV-1 strains, and found that only the Env protein from the R5X4 strain R3A retained some fusion activity. Loss of V1/V2 (DeltaV1/V2) was well tolerated by this virus. Passaging of virus with the truncated V3 loop resulted in the derivation of a virus strain that replicated with wild-type kinetics. This virus, termed TA1, retained the V3 loop truncation and acquired several adaptive changes in gp120 and gp41. TA1 could use CCR5 but not CXCR4 to infect cells, and was extremely sensitive to neutralization by HIV-1 positive human sera, and by antibodies to the CD4 binding site and to CD4-induced epitopes in the bridging sheet region of gp120. In addition, TA1 was completely resistant to CCR5 inhibitors, and was more dependent upon the N-terminal domain of CCR5, a region of the receptor that is thought to contact the bridging sheet of gp120 and the base of the V3 loop, and whose conformation may not be greatly affected by CCR5 inhibitors. These studies suggest that the V3 loop protects HIV from neutralization by antibodies prevalent in infected humans, that CCR5 inhibitors likely act by disrupting interactions between the V3 loop and the coreceptor, and that altered use of CCR5 by HIV-1 associated with increased sensitivity to changes in the N-terminal domain can be linked to high levels of resistance to these antiviral compounds. PMID- 17722978 TI - Nod1 signaling overcomes resistance of S. pneumoniae to opsonophagocytic killing. AB - Airway infection by the Gram-positive pathogen Streptococcus pneumoniae (Sp) leads to recruitment of neutrophils but limited bacterial killing by these cells. Co-colonization by Sp and a Gram-negative species, Haemophilus influenzae (Hi), provides sufficient stimulus to induce neutrophil and complement-mediated clearance of Sp from the mucosal surface in a murine model. Products from Hi, but not Sp, also promote killing of Sp by ex vivo neutrophil-enriched peritoneal exudate cells. Here we identify the stimulus from Hi as its peptidoglycan. Enhancement of opsonophagocytic killing was facilitated by signaling through nucleotide-binding oligomerization domain-1 (Nod1), which is involved in recognition of gamma-D-glutamyl-meso-diaminopimelic acid (meso-DAP) contained in cell walls of Hi but not Sp. Neutrophils from mice treated with Hi or compounds containing meso-DAP, including synthetic peptidoglycan fragments, showed increased Sp killing in a Nod1-dependent manner. Moreover, Nod1(-/-) mice showed reduced Hi-induced clearance of Sp during co-colonization. These observations offer insight into mechanisms of microbial competition and demonstrate the importance of Nod1 in neutrophil-mediated clearance of bacteria in vivo. PMID- 17722979 TI - Genome dynamics of Campylobacter jejuni in response to bacteriophage predation. AB - Campylobacter jejuni is a leading cause of food-borne illness. Although a natural reservoir of the pathogen is domestic poultry, the degree of genomic diversity exhibited by the species limits the application of epidemiological methods to trace specific infection sources. Bacteriophage predation is a common burden placed upon C. jejuni populations in the avian gut, and we show that amongst C. jejuni that survive bacteriophage predation in broiler chickens are bacteriophage resistant types that display clear evidence of genomic rearrangements. These rearrangements were identified as intra-genomic inversions between Mu-like prophage DNA sequences to invert genomic segments up to 590 kb in size, the equivalent of one-third of the genome. The resulting strains exhibit three clear phenotypes: resistance to infection by virulent bacteriophage, inefficient colonisation of the broiler chicken intestine, and the production of infectious bacteriophage CampMu. These genotypes were recovered from chickens in the presence of virulent bacteriophage but not in vitro. Reintroduction of these strains into chickens in the absence of bacteriophage results in further genomic rearrangements at the same locations, leading to reversion to bacteriophage sensitivity and colonisation proficiency. These findings indicate a previously unsuspected method by which C. jejuni can generate genomic diversity associated with selective phenotypes. Genomic instability of C. jejuni in the avian gut has been adopted as a mechanism to temporarily survive bacteriophage predation and subsequent competition for resources, and would suggest that C. jejuni exists in vivo as families of related meta-genomes generated to survive local environmental pressures. PMID- 17722981 TI - Role of dendritic cells in differential susceptibility to viral demyelinating disease. AB - Although persistent viral diseases are a global health concern, the mechanisms of differential susceptibility to such infections among individuals are unknown. Here, we report that differential interactions between dendritic cells (DCs) and virus are critical in determining resistance versus susceptibility in the Theiler murine encephalomyelitis virus-induced demyelinating disease model of multiple sclerosis. This virus induces a chronic demyelinating disease in susceptible mice, whereas the virus is completely cleared in resistant strains of mice. DCs from susceptible mice are more permissive to viral infection, resulting in severe deficiencies in development, expansion, and function, in contrast to DCs from resistant mice. Although protective prior to viral infection, higher levels of type I interferons (IFNs) and IFN-gamma produced by virus-infected DCs from susceptible mice further contribute to the differential inhibition of DC development and function. An increased DC number and/or acquired resistance of DCs to viral infection render susceptible mice resistant to viral persistence and disease progression. Thus, the differential permissiveness of DCs to infectious agents and its subsequent functional and developmental deficiencies determine the outcome of infection- associated diseases. Therefore, arming DCs against viral infection-induced functional decline may provide a useful intervention for chronic infection-associated diseases. PMID- 17722980 TI - Natural killer cells promote early CD8 T cell responses against cytomegalovirus. AB - Understanding the mechanisms that help promote protective immune responses to pathogens is a major challenge in biomedical research and an important goal for the design of innovative therapeutic or vaccination strategies. While natural killer (NK) cells can directly contribute to the control of viral replication, whether, and how, they may help orchestrate global antiviral defense is largely unknown. To address this question, we took advantage of the well-defined molecular interactions involved in the recognition of mouse cytomegalovirus (MCMV) by NK cells. By using congenic or mutant mice and wild-type versus genetically engineered viruses, we examined the consequences on antiviral CD8 T cell responses of specific defects in the ability of the NK cells to control MCMV. This system allowed us to demonstrate, to our knowledge for the first time, that NK cells accelerate CD8 T cell responses against a viral infection in vivo. Moreover, we identify the underlying mechanism as the ability of NK cells to limit IFN-alpha/beta production to levels not immunosuppressive to the host. This is achieved through the early control of cytomegalovirus, which dramatically reduces the activation of plasmacytoid dendritic cells (pDCs) for cytokine production, preserves the conventional dendritic cell (cDC) compartment, and accelerates antiviral CD8 T cell responses. Conversely, exogenous IFN-alpha administration in resistant animals ablates cDCs and delays CD8 T cell activation in the face of NK cell control of viral replication. Collectively, our data demonstrate that the ability of NK cells to respond very early to cytomegalovirus infection critically contributes to balance the intensity of other innate immune responses, which dampens early immunopathology and promotes optimal initiation of antiviral CD8 T cell responses. Thus, the extent to which NK cell responses benefit the host goes beyond their direct antiviral effects and extends to the prevention of innate cytokine shock and to the promotion of adaptive immunity. PMID- 17722982 TI - Genome analysis of Minibacterium massiliensis highlights the convergent evolution of water-living bacteria. AB - Filtration usually eliminates water-living bacteria. Here, we report on the complete genome sequence of Minibacterium massiliensis, a beta-proteobacteria that was recovered from 0.22-mum filtered water used for patients in the hospital. The unexpectedly large 4,110,251-nucleotide genome sequence of M. massiliensis was determined using the traditional shotgun sequencing approach. Bioinformatic analyses shows that the M. massiliensis genome sequence illustrates characteristic features of water-living bacteria, including overrepresentation of genes encoding transporters and transcription regulators. Phylogenomic analysis based on the gene content of available bacterial genome sequences displays a congruent evolution of water-living bacteria from various taxonomic origins, principally for genes involved in energy production and conversion, cell division, chromosome partitioning, and lipid metabolism. This phylogenomic clustering partially results from lateral gene transfer, which appears to be more frequent in water than in other environments. The M. massiliensis genome analyses strongly suggest that water-living bacteria are a common source for genes involved in heavy-metal resistance, antibiotics resistance, and virulence factors. PMID- 17722983 TI - Early endocardial morphogenesis requires Scl/Tal1. AB - The primitive heart tube is composed of an outer myocardial and an inner endocardial layer that will give rise to the cardiac valves and septa. Specification and differentiation of these two cell layers are among the earliest events in heart development, but the embryonic origins and genetic regulation of early endocardial development remain largely undefined. We have analyzed early endocardial development in the zebrafish using time-lapse confocal microscopy and show that the endocardium seems to originate from a region in the lateral plate mesoderm that will give rise to hematopoietic cells of the primitive myeloid lineage. Endocardial precursors appear to rapidly migrate to the site of heart tube formation, where they arrive prior to the bilateral myocardial primordia. Analysis of a newly discovered zebrafish Scl/Tal1 mutant showed an additional and previously undescribed role of this transcription factor during the development of the endocardium. In Scl/Tal1 mutant embryos, endocardial precursors are specified, but migration is severely defective and endocardial cells aggregate at the ventricular pole of the heart. We further show that the initial fusion of the bilateral myocardial precursor populations occurs independently of the endocardium and tal1 function. Our results suggest early separation of the two components of the primitive heart tube and imply Scl/Tal1 as an indispensable component of the molecular hierarchy that controls endocardium morphogenesis. PMID- 17722985 TI - Assessing the significance of conserved genomic aberrations using high resolution genomic microarrays. AB - Genomic aberrations recurrent in a particular cancer type can be important prognostic markers for tumor progression. Typically in early tumorigenesis, cells incur a breakdown of the DNA replication machinery that results in an accumulation of genomic aberrations in the form of duplications, deletions, translocations, and other genomic alterations. Microarray methods allow for finer mapping of these aberrations than has previously been possible; however, data processing and analysis methods have not taken full advantage of this higher resolution. Attention has primarily been given to analysis on the single sample level, where multiple adjacent probes are necessarily used as replicates for the local region containing their target sequences. However, regions of concordant aberration can be short enough to be detected by only one, or very few, array elements. We describe a method called Multiple Sample Analysis for assessing the significance of concordant genomic aberrations across multiple experiments that does not require a-priori definition of aberration calls for each sample. If there are multiple samples, representing a class, then by exploiting the replication across samples our method can detect concordant aberrations at much higher resolution than can be derived from current single sample approaches. Additionally, this method provides a meaningful approach to addressing population based questions such as determining important regions for a cancer subtype of interest or determining regions of copy number variation in a population. Multiple Sample Analysis also provides single sample aberration calls in the locations of significant concordance, producing high resolution calls per sample, in concordant regions. The approach is demonstrated on a dataset representing a challenging but important resource: breast tumors that have been formalin-fixed, paraffin-embedded, archived, and subsequently UV-laser capture microdissected and hybridized to two-channel BAC arrays using an amplification protocol. We demonstrate the accurate detection on simulated data, and on real datasets involving known regions of aberration within subtypes of breast cancer at a resolution consistent with that of the array. Similarly, we apply our method to previously published datasets, including a 250K SNP array, and verify known results as well as detect novel regions of concordant aberration. The algorithm has been fully implemented and tested and is freely available as a Java application at http://www.cbil.upenn.edu/MSA. PMID- 17722984 TI - A discrete class of intergenic DNA dictates meiotic DNA break hotspots in fission yeast. AB - Meiotic recombination is initiated by DNA double-strand breaks (DSBs) made by Spo11 (Rec12 in fission yeast), which becomes covalently linked to the DSB ends. Like recombination events, DSBs occur at hotspots in the genome, but the genetic factors responsible for most hotspots have remained elusive. Here we describe in fission yeast the genome-wide distribution of meiosis-specific Rec12-DNA linkages, which closely parallel DSBs measured by conventional Southern blot hybridization. Prominent DSB hotspots are located approximately 65 kb apart, separated by intervals with little or no detectable breakage. Most hotspots lie within exceptionally large intergenic regions. Thus, the chromosomal architecture responsible for hotspots in fission yeast is markedly different from that of budding yeast, in which DSB hotspots are much more closely spaced and, in many regions of the genome, occur at each promoter. Our analysis in fission yeast reveals a clearly identifiable chromosomal feature that can predict the majority of recombination hotspots across a whole genome and provides a basis for searching for the chromosomal features that dictate hotspots of meiotic recombination in other organisms, including humans. PMID- 17722987 TI - Casuistry and the moral continuum. Evaluating animal biotechnology. AB - While the science of animal biotechnology is advancing at a rapid pace, the ethical discussion about the boundaries the public might want to set is at the most nascent stage. There is a tendency in the public debate for opponents to favor an all-out ban on the science, while proponents want to grant it carte blanche. I argue that a more nuanced position on animal biotechnology considers individual projects to be located on a moral continuum, where some are clearly morally justified, others morally impermissible, and some lie in the ethical gray zone. To begin to define this continuum, we use the bioethical method of casuistry to analyze one case at the end of moral permissibility, and we contrast it with a case that is located at the opposite end of the moral spectrum. I advocate this approach to assessing the moral merit of biotechnology projects because of its attention to the details of individual cases--the protocols, ends, and methods--on which an accurate moral judgment necessarily rests. PMID- 17722989 TI - Evolving political science. Biological adaptation, rational action, and symbolism. AB - Political science, as a discipline, has been reluctant to adopt theories and methodologies developed in fields studying human behavior from an evolutionary standpoint. I ask whether evolutionary concepts are reconcilable with standard political-science theories and whether those concepts help solve puzzles to which these theories classically are applied. I find that evolutionary concepts readily and simultaneously accommodate theories of rational choice, symbolism, interpretation, and acculturation. Moreover, phenomena perennially hard to explain in standard political science become clearer when human interactions are understood in light of natural selection and evolutionary psychology. These phenomena include the political and economic effects of emotion, status, personal attractiveness, and variations in information-processing and decision-making under uncertainty; exemplary is the use of "focal points" in multiple-equilibrium games. I conclude with an overview of recent research by, and ongoing debates among, scholars analyzing politics in evolutionarily sophisticated terms. PMID- 17722986 TI - Linkage disequilibrium in wild mice. AB - Crosses between laboratory strains of mice provide a powerful way of detecting quantitative trait loci for complex traits related to human disease. Hundreds of these loci have been detected, but only a small number of the underlying causative genes have been identified. The main difficulty is the extensive linkage disequilibrium (LD) in intercross progeny and the slow process of fine scale mapping by traditional methods. Recently, new approaches have been introduced, such as association studies with inbred lines and multigenerational crosses. These approaches are very useful for interval reduction, but generally do not provide single-gene resolution because of strong LD extending over one to several megabases. Here, we investigate the genetic structure of a natural population of mice in Arizona to determine its suitability for fine-scale LD mapping and association studies. There are three main findings: (1) Arizona mice have a high level of genetic variation, which includes a large fraction of the sequence variation present in classical strains of laboratory mice; (2) they show clear evidence of local inbreeding but appear to lack stable population structure across the study area; and (3) LD decays with distance at a rate similar to human populations, which is considerably more rapid than in laboratory populations of mice. Strong associations in Arizona mice are limited primarily to markers less than 100 kb apart, which provides the possibility of fine-scale association mapping at the level of one or a few genes. Although other considerations, such as sample size requirements and marker discovery, are serious issues in the implementation of association studies, the genetic variation and LD results indicate that wild mice could provide a useful tool for identifying genes that cause variation in complex traits. PMID- 17722990 TI - Stephen Jay Gould as a political theorist. AB - Before his death in 2002, paleontologist Stephen Jay Gould elaborated a large and inclusive theory of life's change. In this essay I concentrate on the aspects of Gould's vast theory that have the most direct political relevance. I briefly discuss his views on the philosophy of science. I examine the way he combined political values and methodology in a seamless, critical analysis of intelligence testing and sociobiology. I concentrate most extensively on the impact his "punctuated equilibria" concept has made on contemporary political analysis, and I demonstrate that in their appropriation of this concept political scientists have violated the rules that Gould himself articulated for its use. In closing, I consider the possibility that a comprehensive theory of life, a theory that must include political values, might approach traditional questions of political thought more satisfyingly than has conventional philosophy. PMID- 17722991 TI - Land, ecology, and democracy. A twenty-first century view. AB - Land is necessary for human flourishing, and its use remains a compelling concern for every society, even those wherein industrialization has sharply diminished people's awareness of land. Here, we consider land's influence on political thinking, particularly thinking about democratic governance, and ask if this influence might be made more beneficial by the application of lessons drawn from ecological research. We identify five such lessons and apply them in six ways to the institution of private-property rights in nature--the main legal institution that allocates and perpetuates power over land--and to modern assumptions about liberal individualism and rights to health. We conclude that people can live well on land, promoting both human and land health, only in governmental forms engaging more citizens more deliberatively than now typical even in democracies. Implications for political institutions and human welfare are discussed under conditions of globalizing interdependence. PMID- 17722992 TI - Terrorists and biological weapons. Forging the linkage in the Clinton Administration. AB - By the end of the Clinton administration, the claim that terrorists armed with biological weapons represented a huge threat to the security of the United States had achieved the status of received knowledge. How this linkage was forged, despite informed dissent not only outside the Clinton administration but also within it, and how it was used to justify a radical reframing of biological knowledge, especially in genetic engineering and genomics, in terms of military goals is the subject of this essay. My method is historical. I assume that no category is fixed but, rather, that key terms, such as "weapons of mass destruction," "biological weapon," and "terrorism" itself, are contingent, shaped under specific historical and political circumstances, and are therefore more fluid than often thought. This account draws on a wide variety of sources including government documents, policy papers and books, conference records, media materials, memoirs, and detailed interviews with nine subjects selected from among participants in the events examined. It shows that the nature of a linkage between terrorism and biological weaponry was debated at many levels in Washington, and it offers reasons why, ultimately, a counterbioterrorism "bandwagon" was constructed and began rolling at the end of the second Clinton administration. PMID- 17722993 TI - Prolonged increase in T-cell receptor (TCR) variant fractions of spleen T lymphocytes in pregnant mice after gamma irradiation. AB - To investigate the relationship between the radiation-induced increase of T-cell receptor (TCR) defective variant fractions and physiological status such as pregnancy, C57BL/ 6N mice were irradiated with 3 Gy of gamma rays at various days of gestation, just before and just after pregnancy. While the highest level of variant fractions in spleen T lymphocytes appeared at 9 days postirradiation and resolved fairly rapidly for nonpregnant mice, the increased variant fractions for pregnant mice irradiated at 16.5 days of gestation reached a plateau at 14 days postirradiation and remained at high levels until 28 days after irradiation. Therefore, variant fractions 28 days postirradiation were measured to determine the overall effect of radiation on the kinetics of TCR variant fractions during gestation. There was no significant difference in the baseline TCR variant fraction between unirradiated nonpregnant and pregnant mice. TCR variant fractions after irradiation were about twofold higher in pregnant mice (from 10.5 days of gestation until delivery) than those in nonpregnant mice. Both gamma radiation and pregnancy caused a decrease in the proportion of naive T-cell subsets and an increase in TCR variant fractions of naive T cells. In addition, the prolonged postirradiation increase in the TCR variant fractions of pregnant mice was associated with an increase in serum progesterone level. Differences between pregnant and nonpregnant mice in the kinetics of postirradiation restoration of T-cell systems may be involved in producing the differences in residual TCR variant fractions of these mice. PMID- 17722994 TI - Advantage of combining NLCQ-1 (NSC 709257) with radiation in treatment of human head and neck xenografts. AB - NLCQ-1 (NSC 709257), a hypoxia-selective cytotoxin that targets DNA through weak intercalation, was investigated for efficacy in combination with single or fractionated radiotherapy of human head and neck xenografts. A staged tumor experiment was performed in tumor-bearing female athymic nude mice that were locally irradiated with or without NLCQ-1. Tumor hypoxia was assessed by immunohistochemistry for pimonidazole adducts in tumors of varying weight. Fractionated radiation, depending on the dose, was administered either once daily for 4 days or once daily for 4 days followed by a 7-day rest and repeat. NLCQ-1 was administered i.p. at 15 mg/kg alone or 45 min before each radiation dose. Hypoxia (1-52%) was detected in all tumors and was positively correlated with tumor size. NLCQ-1 alone resulted in about 10 days of tumor growth delay, measured at sixfold the tumor's original size, without causing toxicity. All combination treatments with NLCQ-1 were more effective than treatments with radiation alone. Radiation at 1 Gy given once daily for 4 days on days 20 and 30 caused 3.5 days of tumor growth delay, whereas in combination with NLCQ-1 it caused 14.5 days of growth delay. Radiation at 5 Gy given in two doses 10 days apart resulted in 3.5 days of tumor growth delay, whereas more than 20 additional days of delay were observed in combination with NLCQ-1. Radiation given as a single dose of 10 Gy resulted in about 7 days of tumor growth delay, whereas in combination with NLCQ-1 about 30 additional days of delay were seen. These results suggest a significant advantage in combining radiation with NLCQ-1 in treatment of human head and neck tumors, which are known to have hypoxic areas. PMID- 17722995 TI - mBAND analysis of chromosomal aberrations in human epithelial cells exposed to low- and high-LET radiation. AB - Energetic heavy ions pose a potential health risk to astronauts who have participated in extended space missions. High-LET radiation is much more effective than low-LET radiation in the induction of biological effects, including cell inactivation, genetic mutations, cataracts and cancer. Most of these biological end points are closely correlated with chromosomal damage, which can be used as a biomarker for radiation damage. Multicolor banding in situ hybridization (mBAND) has proven to be highly useful for the study of intrachromosomal aberrations, which have been suggested as a biomarker of exposure to high-LET radiation. To investigate biological signatures of radiation quality and the complexity of intrachromosomal aberrations, we exposed human epithelial cells in vitro to (137)Cs gamma rays or iron ions (600 MeV/nucleon) and collected chromosomes using a premature chromosome condensation technique. Aberrations in chromosome 3 were analyzed using mBAND probes. The results of our study confirmed the observation of a higher incidence of inversions for high-LET radiation. However, detailed analysis of the inversion type revealed that both iron ions and gamma rays induced a low incidence of simple inversions. Half of the inversions observed in the low-LET-irradiated samples were accompanied by other types of intrachromosome aberrations, but few inversions were accompanied by interchromosome aberrations. In contrast, iron ions induced a significant fraction of inversions that involved complex rearrangements of both inter- and intrachromosome exchanges. PMID- 17722996 TI - Solid cancer incidence in atomic bomb survivors: 1958-1998. AB - This is the second general report on radiation effects on the incidence of solid cancers (cancers other than malignancies of the blood or blood-forming organs) among members of the Life Span Study (LSS) cohort of Hiroshima and Nagasaki atomic bomb survivors. The analyses were based on 17,448 first primary cancers (including non-melanoma skin cancer) diagnosed from 1958 through 1998 among 105,427 cohort members with individual dose estimates who were alive and not known to have had cancer prior to 1958. Radiation-associated relative risks and excess rates were considered for all solid cancers as a group, for 19 specific cancer sites or groups of sites, and for five histology groups. Poisson regression methods were used to investigate the magnitude of the radiation associated risks, the shape of the dose response, how these risks vary with gender, age at exposure, and attained age, and the evidence for inter-site variation in the levels and patterns of the excess risk. For all solid cancers as a group, it was estimated that about 850 (about 11%) of the cases among cohort members with colon doses in excess of 0.005 Gy were associated with atomic bomb radiation exposure. The data were consistent with a linear dose response over the 0- to 2-Gy range, while there was some flattening of the dose response at higher doses. Furthermore, there is a statistically significant dose response when analyses were limited to cohort members with doses of 0.15 Gy or less. The excess risks for all solid cancers as a group and many individual sites exhibit significant variation with gender, attained age, and age at exposure. It was estimated that, at age 70 after exposure at age 30, solid cancer rates increase by about 35% per Gy (90% CI 28%; 43%) for men and 58% per Gy (43%; 69%) for women. For all solid cancers as a group, the excess relative risk (ERR per Gy) decreases by about 17% per decade increase in age at exposure (90% CI 7%; 25%) after allowing for attained-age effects, while the ERR decreased in proportion to attained age to the power 1.65 (90% CI 2.1; 1.2) after allowing for age at exposure. Despite the decline in the ERR with attained age, excess absolute rates appeared to increase throughout the study period, providing further evidence that radiation-associated increases in cancer rates persist throughout life regardless of age at exposure. For all solid cancers as a group, women had somewhat higher excess absolute rates than men (F:M ratio 1.4; 90% CI 1.1; 1.8), but this difference disappears when the analysis was restricted to non-gender-specific cancers. Significant radiation-associated increases in risk were seen for most sites, including oral cavity, esophagus, stomach, colon, liver, lung, non melanoma skin, breast, ovary, bladder, nervous system and thyroid. Although there was no indication of a statistically significant dose response for cancers of the pancreas, prostate and kidney, the excess relative risks for these sites were also consistent with that for all solid cancers as a group. Dose-response estimates for cancers of the rectum, gallbladder and uterus were not statistically significant, and there were suggestions that the risks for these sites may be lower than those for all solid cancers combined. However, there was emerging evidence from the present data that exposure as a child may increase risks of cancer of the body of the uterus. Elevated risks were seen for all of the five broadly classified histological groups considered, including squamous cell carcinoma, adenocarcinoma, other epithelial cancers, sarcomas and other non epithelial cancers. Although the data were limited, there was a significant radiation-associated increase in the risk of cancer occurring in adolescence and young adulthood. In view of the persisting increase in solid cancer risks, the LSS should continue to provide important new information on radiation exposure and solid cancer risks for at least another 15 to 20 years. PMID- 17722997 TI - Increased mitochondrial mass in cells with functionally compromised mitochondria after exposure to both direct gamma radiation and bystander factors. AB - The bystander effect describes radiation-like damage in unirradiated cells either in the vicinity of irradiated cells or exposed to medium from irradiated cells. This study aimed to further characterize the poorly understood mitochondrial response to both direct irradiation and bystander factor(s) in human keratinocytes (HPV-G) and Chinese hamster ovarian cells (CHO-K1). Oxygen consumption rates were determined during periods of state 4, state 3 and uncoupled respiration. Mitochondrial mass was determined using MitoTracker FM. CHO-K1 cells showed significantly reduced oxygen consumption rates 4 h after exposure to 5 Gy direct radiation and irradiated cell conditioned medium (ICCM) and an apparent recovery 12-24 h later. The apparent recovery was likely due to the substantial increase in mitochondrial mass observed in these cells as soon as 4 h after exposure. HPV-G cells, on the other hand, showed a sustained increase in oxygen consumption rates after ICCM exposure and a transient increase 4 h after exposure to 5 Gy direct radiation. A significant increase in mitochondrial mass per HPV-G cell was observed after exposure to both direct radiation and ICCM. These findings are indicative of a stress response to mitochondrial dysfunction that increases the number of mitochondria per cell. PMID- 17722998 TI - Attenuated DNA damage repair by trichostatin A through BRCA1 suppression. AB - Recent studies have demonstrated that some histone deacetylase (HDAC) inhibitors enhance cellular radiation sensitivity. However, the underlying mechanism for such a radiosensitizing effect remains unexplored. Here we show evidence that treatment with the HDAC inhibitor trichostatin A (TSA) impairs radiation-induced repair of DNA damage. The effect of TSA on the kinetics of DNA damage repair was measured by performing the comet assay and gamma-H2AX focus analysis in radioresistant human squamous carcinoma cells (SQ-20B). TSA exposure increased the amount of radiation-induced DNA damage and slowed the repair kinetics. Gene expression profiling also revealed that a majority of the genes that control cell cycle, DNA replication and damage repair processes were down-regulated after TSA exposure, including BRCA1. The involvement of BRCA1 was further demonstrated by expressing ectopic wild-type BRCA1 in a BRCA1 null cell line (HCC-1937). TSA treatment enhanced radiation sensitivity of HCC-1937/wtBRCA1 clonal cells, which restored cellular radiosensitivity (D(0) = 1.63 Gy), to the control level (D(0) = 1.03 Gy). However, TSA had no effect on the level of radiosensitivity of BRCA1 null cells. Our data demonstrate for the first time that TSA treatment modulates the radiation-induced DNA damage repair process, in part by suppressing BRCA1 gene expression, suggesting that BRCA1 is one of molecular targets of TSA. PMID- 17723000 TI - Lymphoma development in mice chronically exposed to UMTS-modulated radiofrequency electromagnetic fields. AB - There are public concerns regarding possible carcinogenic or cancer-promoting effects of electromagnetic fields (EMFs) from mobile phones and base stations. The objective of the present study was to investigate whether chronic exposure to EMFs of the UMTS (Universal Mobile Telecommunication System) influences the development of lymphoma in a lymphoma animal model, the AKR/J mouse. Unrestrained mice were chronically sham-exposed (n = 160) or exposed (n = 160) in identical exposure systems (radial waveguides) to a generic UMTS test signal (24 h per day, 7 days per week, 0.4 W/kg SAR). Additionally, 30 animals were kept as cage controls. Animals were checked visually each day and were weighed and palpated weekly to detect swollen lymph nodes. Starting at the age of 6 months, blood samples were taken from the tail every 2 weeks to perform differential leukocyte counts and to measure the hematocrit. Visibly diseased animals or those older than 43 weeks were killed humanely, and tissue slices were examined for metastatic infiltrations and lymphoma type. The study was performed in a blinded way. Cage control animals had a significantly lower growth rate than those kept in the radial waveguides. The number of ill animals, the mean survival time, and the severity code of the disease did not differ between the experimental groups. Therefore, the data show no negative effects from exposure and corroborate earlier findings in AKR/J mice exposed to GSM EMF (Sommer et al., BMC Cancer 4, 77-90, 2004). PMID- 17722999 TI - Targeting integrins and PI3K/Akt-mediated signal transduction pathways enhances radiation-induced anti-angiogenesis. AB - The integrins and PI3K/Akt are important mediators of the signal transduction pathways involved in tumor angiogenesis and cell survival after exposure to ionizing radiation. Selective targeting of either integrins or PI3K/Akt can radiosensitize tumors. In this study, we tested the hypothesis that the combined inhibition of integrin alphanubeta3 by cRGD and PI3K/Akt by LY294002 would significantly enhance radiation-induced inhibition of angiogenesis by vascular endothelial cells. Treatment with cRGD inhibited the adhesion and tube formation of human umbilical vein endothelial cells (HUVECs). The inhibitory effect was further increased when cRGD and LY294002 were applied simultaneously. Both radiation and cRGD induced Akt phosphorylation, up-regulated COX2 expression, and increased PGE2 production in HUVECs. Treatment with LY294002 effectively inhibited radiation- and cRGD-induced Akt phosphorylation and up-regulation of COX2 and increased apoptosis of HUVECs. The combined use of cRGD and LY294002 enhanced radiation-induced cell killing. The clonogenic survival of HUVECs was decreased from 34% with 2 Gy radiation to 4% with these agents combined. These results demonstrate that combined use of ionizing radiation, cRGD and LY294002 inhibited multiple signaling transduction pathways involved in tumor angiogenesis and enhanced radiation-induced effects on vascular endothelial cells. PMID- 17723001 TI - Induction and processing of oxidative clustered DNA lesions in 56Fe-ion irradiated human monocytes. AB - Space and cosmic radiation is characterized by energetic heavy ions of high linear energy transfer (LET). Although both low- and high-LET radiations can create oxidative clustered DNA lesions and double-strand breaks (DSBs), the local complexity of oxidative clustered DNA lesions tends to increase with increasing LET. We irradiated 28SC human monocytes with doses from 0-10 Gy of (56)Fe ions (1.046 GeV/ nucleon, LET = 148 keV/microm) and determined the induction and processing of prompt DSBs and oxidative clustered DNA lesions using pulsed-field gel electrophoresis (PFGE) and Number Average Length Analysis (NALA). The (56)Fe ions produced decreased yields of DSBs (10.9 DSB Gy(-1) Gbp(-1)) and clusters (1 DSB: approximately 0.8 Fpg clusters: approximately 0.7 Endo III clusters: approximately 0.5 Endo IV clusters) compared to previous results with (137)Cs gamma rays. The difference in the relative biological effectiveness (RBE) of the measured and predicted DSB yields may be due to the formation of spatially correlated DSBs (regionally multiply damaged sites) which result in small DNA fragments that are difficult to detect with the PFGE assay. The processing data suggest enhanced difficulty compared with gamma rays in the processing of DSBs but not clusters. At the same time, apoptosis is increased compared to that seen with gamma rays. The enhanced levels of apoptosis observed after exposure to (56)Fe ions may be due to the elimination of cells carrying high levels of persistent DNA clusters that are removed only by cell death and/or "splitting" during DNA replication. PMID- 17723003 TI - Thoracic CT findings following endovascular stent-graft treatment for thoracic aortic aneurysm. AB - PURPOSE: To investigate the transient computed tomographic (CT) findings and morphological characteristics of the descending thoracic aorta following endovascular repair of thoracic aortic aneurysm (TAA). METHODS: Of 50 TAAs repaired using custom-made endoprostheses between May 1997 and September 2005, 35 (25 men; mean age 67 years) were successfully treated and followed for >3 months by thoracic CT. The TAA etiologies were 22 degenerative/atherosclerotic, 7 dissection-related from intramural hematoma, 2 traumatic, 2 anastomotic, and 2 penetrating ulcers. The CT findings following stent-graft placement were retrospectively studied. RESULTS: Over a mean follow-up of 27.0+/-25 months (range 3-92), periaortic changes were observed in 17 (48.6%) patients, and the amount of pleural effusion increased in 13 (37.1%). In all cases, these findings disappeared without specific treatment during the follow-up period. Late secondary endoleak was observed in 1 (2.9%) patient, and there was 1 (2.9%) caudal migration of the proximal end of the stent-graft. Five (14.3%) aneurysms increased in size. Two patients, both with dissection, showed aortic neck dilatation. There was a positive relationship between neck dilatation and dissection-related TAA etiology (p = 0.035). CONCLUSION: Although aortic neck dilatation is less common after endovascular TAA repair than after abdominal repairs, patients with dissection-related TAA may be a subgroup prone to aneurysm neck dilatation. PMID- 17723004 TI - Deteriorating consumptive coagulopathy with type III endoleak following endovascular repair for abdominal aortic aneurysm associated with liver cirrhosis. AB - PURPOSE: To report a case of deteriorating consumptive coagulopathy with type III endoleak following endovascular aneurysm repair (EVAR) of the abdominal aorta associated with liver cirrhosis. CASE REPORT: A 72-year-old man with liver cirrhosis developed type III endoleak following EVAR. Spontaneous intramuscular hematoma developed due to deteriorating consumptive coagulopathy induced by type III endoleak and liver dysfunction. Although additional EVAR was performed at 52 months after primary EVAR, the patient died due to multiorgan failure and multifocal hematoma of the muscles and subserosa. CONCLUSION: EVAR for patients with liver dysfunction and coagulopathy should be considered with great caution. We suggest that prompt and adequate treatment using an endovascular technique or surgical repair should be performed for patients with liver dysfunction, coagulopathy, and turbulent endoleak, even if the coagulopathies are worse compared to before EVAR. PMID- 17723002 TI - Relationship between phosphorylated histone H2AX formation and cell survival in human microvascular endothelial cells (HMEC) as a function of ionizing radiation exposure in the presence or absence of thiol-containing drugs. AB - Human microvascular endothelial cells (HMEC) were exposed to ionizing radiation at doses ranging from 0 to 16 Gy in either the presence or absence of the active thiol forms of amifostine (WR1065), phosphonol (WR255591), N-acetyl-l-cysteine (NAC), captopril or mesna. Each of these clinically relevant thiols, administered to HMEC at a dose of 4 mM for 30 min prior to irradiation, is known to exhibit antioxidant properties. The purpose of this investigation was to determine the relationship(s), if any, between the frequency of radiation-induced histone H2AX phosphorylation at serine 139 (gamma-H2AX) in cells and subsequent survival, as assessed by colony-forming ability, in exposed cell populations as a function of the presence or absence of each of the five thiol compounds during irradiation. gamma-H2AX formation in irradiated cells, as a function of relative DNA content, was quantified by bivariant flow cytometry analysis with FITC-conjugated gamma H2AX antibody and nuclear DAPI staining. gamma-H2AX formation in cells was measured as the relative fold increase as a function of the treatment conditions. The frequency of gamma-H2AX-positive cells increased with increasing dose of radiation followed by a dose- and time-dependent decay. The most robust response for gamma-H2AX formation occurred 1 h after irradiation with their relative frequencies decreasing as a function of time 4 and 24 h later. To assess the effects of the various thiols on gamma-H2AX formation, all measurements were made 1 h after irradiation. WR1065 was not only effective in protecting HMEC against gamma-H2AX formation across the entire dose range of radiation exposures used, but it was also significantly more cytoprotective than either its prodrug (WR2721) or disulfide (WR33278) analogue. WR1065 had no significant effect on gamma-H2AX formation when administered immediately or up to 30 min after radiation exposure. An inhibitory effect against gamma-H2AX formation induced by 8 Gy of radiation was expressed by each of the thiols tested. NAC, captopril and mesna were equally effective in reducing the frequency of gamma-H2AX formation, with both WR1065 and WR255591 exhibiting a slightly more robust protective effect. Each of the five thiols was effective in reducing the frequency of gamma H2AX-positive cells across all phases of the cell cycle. In contrast to the relative ability of each of these thiols to inhibit gamma-H2AX formation after irradiation, NAC, captopril and mesna afforded no protection to HMEC as determined using a colony-forming survival assay. Only WR1065 and WR255591 were effective in reducing the frequencies of radiation-induced gamma-H2AX-positive cells as well as protecting against cell death. These results suggest that the use of gamma-H2AX as a biomarker for screening the efficacy of novel antioxidant radioprotective compounds is highly problematic since their formation and disappearance may be linked to processes beyond simply the formation and repair of radiation-induced DSBs. PMID- 17723005 TI - Multidetector CT angiography in the follow-up of patients treated with renal artery stents: value of different reformation techniques compared with axial source images. AB - PURPOSE: To evaluate the role of 4 different reformation techniques in comparison with axial images from multidetector computed tomographic angiography (MDCTA) in the follow-up of renal artery stents. METHODS: Data on 40 patients (20 men; mean age 65 years) who underwent MDCTA as part of their routine follow-up after successful primary stenting of a main renal artery were retrospectively analyzed. Multiplanar reformation (MPR), curved planar reformation (CPR), volume rendering threshold (VRT), and virtual angioscopy (VA) were reviewed by 2 independent observers who were blinded to the results of the axial source images, which served as the gold standard. The stenosis degree was scored as I = 0%, II <50%, III = 51%-75%, IV = 76%-99%, or V = occlusion; a stenosis >50% was considered hemodynamically significant. RESULTS: Five hemodynamically significant stenoses were identified on axial images. The correlation with axial images was perfect for both observers using MPR and CPR (kappa = 1 for each observer); corresponding results were kappa = 0.69 and kappa = 0.64 for VRT and kappa = 0.88 and kappa = 0.83 for VA, respectively. The interobserver correlations were excellent for all reformation techniques (kappa = 0.95 to 1). CONCLUSION: Compared to axial images, MPR and CPR correlated perfectly with axial images; VA performed surprisingly well, while VRT was affected by artifacts and consequently showed inferior results. PMID- 17723006 TI - Improved technical success and midterm patency with subintimal angioplasty compared to intraluminal angioplasty in long femoropopliteal occlusions. AB - PURPOSE: To compare the efficacy of subintimal angioplasty combined with primary stenting to intraluminal angioplasty with stenting for revascularization of long (>10 cm) femoropopliteal arterial occlusions. METHODS: Baseline characteristics and outcomes of 52 patients (40 men; mean age 65.6+/-9.7 years) with superficial femoral artery (SFA) occlusions in 61 limbs (mean occlusion length 22.7+/-9.9 cm) treated with subintimal angioplasty and primary stenting were compared with a 54 patient control group (46 men; mean age 64.8+/-8.2 years) from our registry database who had intraluminal angioplasty with stenting in 60 limbs (mean occlusion length 22.0+/-8.5 cm). RESULTS: All baseline clinical and angiographic characteristics showed no differences. In all patients, at least 1 self-expanding nitinol stent was implanted. Subintimal angioplasty was successful in 58 (95.1%) of 61 limbs, whereas technical success for the conventional approach was 86.7% (52/60 limbs; p = 0.11). In both groups, there were no major complications requiring surgery. Primary patency at 12 months for successful cases was 76.4% for subintimal angioplasty and 59.2% for conventional angioplasty (p = 0.06); on an intention-to-treat basis, including technical failures, the rates were 72.4% and 50.9%, respectively (p = 0.02). CONCLUSION: Subintimal angioplasty combined with stenting was feasible, with a high technical success rate and better short and midterm results for revascularization of long femoropopliteal occlusions than the conventional intraluminal approach. PMID- 17723007 TI - Periprocedural embolic events related to carotid artery stenting detected by diffusion-weighted MRI: comparison between proximal and distal embolus protection devices. AB - PURPOSE: To evaluate and compare the efficacy of proximal versus distal embolus protection devices (EPD) during carotid artery angioplasty/stenting (CAS) based on diffusion-weighted magnetic resonance imaging (DW-MRI). METHODS: Forty-four patients (31 men; mean age 68 years, range 48-85) underwent protected CAS and had DW-MRI before and after the intervention. The cohort was analyzed according to the type of EPD used: a proximal EPD was deployed in 25 (56.8%) patients (17 men; mean age 66 years, range 48-85) and a distal filter in 19 (14 men; mean age 70 years, range 58-79). Fifteen (60.0%) patients with proximal protection were symptomatic of the target lesion; in the distal protection group, 10 (52.6%) were symptomatic. RESULTS: New lesions were seen on the postinterventional DW-MRI in 28.0% (7/25) of the proximal EPD group versus 32.6% (6/19) of those with a distal filter (p = NS). The majority were clinically silent. The new lesions in the vascular territory of the stented carotid artery in the group as a whole and per patient were fewer in the proximal EPD group (p = NS). No significant differences were noted in the T(2) appearance of the new lesions or the number of new lesions observed away from the vascular territory of the stented artery. CONCLUSION: Proximal embolus protection devices show a nonsignificant trend toward fewer embolic events, which warrants large-scale studies. Furthermore, proximal protection devices can be useful to control and treat acute in-stent thrombosis. PMID- 17723008 TI - Long-term single-center results with AneuRx endografts for endovascular abdominal aortic aneurysm repair. AB - PURPOSE: To evaluate the long-term single-center results with the AneuRx stent graft in endovascular abdominal aortic aneurysm (AAA) repair (EVAR). METHODS: Between December 1996 and August 2003, 212 patients (197 men; mean age 71.3+/-7.0 years) were treated with the AneuRx stent-graft for an infrarenal AAA. Postoperatively, patients were enrolled in a fixed surveillance protocol, and data were prospectively captured into a database. RESULTS: Graft deployment was successful in 98.6% (209/212). Thirty-day mortality was 2.4%. Median hospital stay was 4.3+/-5.5 days. Median follow-up was 52.0 months (range 1-109); only 1 patient was lost to follow-up. At 9 years, patient survival was 56% and freedom from secondary interventions was 48%. In 68% of cases, these reinterventions were needed for a fixation-related complication, and most of these complications (75%) encompassed the area of the proximal aneurysm neck. Primary clinical success was 37% at 9 years. After secondary interventions, the assisted primary clinical success improved to 73% at 9 years. Freedom from aneurysm-related death was 97% at 1 year and 90% at 9 years. CONCLUSION: As an alternative to open repair, EVAR with the AneuRx device has low perioperative mortality. Reinterventions are mostly due to fixation-related complications. While the overall mortality risk in this population was 5% per year, annual aneurysm-related death was only 1%. The focus should be on surveillance and reducing the rate of long-term complications, which might be possible with improved proximal stent-graft fixation. PMID- 17723009 TI - Transpopliteal removal of an OptEase inferior vena cava filter after treatment of symptomatic filter thrombosis. AB - PURPOSE: To describe a case of transpopliteal retrieval of an inferior vena cava (IVC) filter. CASE REPORT: A paraplegic patient had an IVC filter placed for deep venous thrombosis (DVT) after anticoagulant therapy was stopped. Two weeks later, he developed massive scrotal and bilateral lower extremity swelling due to iliocaval thrombosis, which was treated by power pulse-spray thrombectomy and catheter-directed thrombolytic infusion via bilateral popliteal approaches. Following successful thrombus removal, the filter was uniquely retrieved via the right popliteal access; the patient was discharged on warfarin anticoagulation. CONCLUSION: Transpopliteal IVC filter retrieval is feasible and may be a useful alternative technique in selected instances. PMID- 17723010 TI - Aortic neck dilatation and endograft migration are correlated with self-expanding endografts. AB - PURPOSE: To compare self-expanding and balloon-expandable stent-grafts in terms of aortic neck dilatation and endograft migration. METHOD: Two-hundred and forty two patients (178 men; mean age 68 years, range 56-91) underwent elective endovascular repair of abdominal aortic aneurysm. Two-hundred self-expanding (115 Excluder, 48 Endologix, 23 Vanguard, 10 Anaconda, and 4 Talent) and 42 balloon expandable (Lifepath) endografts were used. All patients underwent contrast enhanced computed tomography (CT) prior to the intervention, at 1, 3, and 6 months after the procedure, and annually thereafter. Comparison was made between the first and the last follow-up CT scans. RESULTS: Fifty-five (27.5%) of the 200 patients treated with self-expanding endografts had aortic neck dilatation compared to only 3 (7.1%) of the 42 patients treated with balloon-expandable endografts (p = 0.023). Forty-nine (24.5%) patients in the self-expanding group versus only 3 (7.1%) patients of the balloon-expandable group presented with endograft migration (p = 0.034); all had dilated necks. The difference between the means of neck dilatation for the Lifepath balloon-expandable stent-graft and the Excluder self-expanding endoprosthesis was statistically significant (p = 0.011, 95% CI 0.07 to 0.91). CONCLUSION: Aortic neck dilatation following endovascular AAA repair appears to be correlated with self-expanding endografts, which may contribute to a higher incidence of graft migration compared to that occurring with balloon-expandable endografts. PMID- 17723011 TI - Successful percutaneous angioplasty and stenting of the radial artery in a patient with chronic upper extremity ischemia and digital gangrene. AB - PURPOSE: To report percutaneous treatment of a chronic radial artery occlusion in a multimorbid patient with ischemic tissue loss. CASE REPORT: A 62-year-old man with multiple comorbidities, including renal failure and severe coronary artery disease, presented with painful, ulcerated lesions of his right hand. He has severe peripheral vascular disease, with a history of 4 digital amputations of the left hand, a right above-knee amputation, and a left femoral to peroneal artery bypass. Arteriography demonstrated chronic occlusion of the radial and ulnar arteries, with a patent interosseous and collateral flow to the distal radial artery filling the palmar arch. Angioplasty and stenting of the radial artery was performed, relieving the patient's symptoms and allowing the lesions to heal. CONCLUSION: Percutaneous intervention can treat severe upper extremity ischemia with gangrene in patients with severe chronic ischemia and multiple comorbidities. PMID- 17723012 TI - Iliac conduit for renal and visceral artery access during endovascular repair of a pararenal aneurysm with a fenestrated stent-graft. AB - PURPOSE: To report a technique for fenestrated stent-graft repair involving a conduit implanted at the origin of a patent aneurysmal common iliac artery (CIA) in a patient with a pararenal aortic aneurysm and iliac artery occlusion. CASE REPORT: A 60-year-old man with multiple comorbidities presented with an 8-cm abdominal aortic aneurysm (AAA) with no infrarenal neck according to computed tomography (CT). Both CIAs were aneurysmal; the left was occluded, as were the left internal and external iliac arteries and the inferior mesenteric artery. Two patent accessory renal arteries were depicted. Because an infrarenal neck was absent, treatment with a fenestrated endograft was performed under general anesthesia. The right CIA was approached via an oblique retroperitoneal incision. A 10-mm polytetrafluoroethylene tube graft was implanted on the origin of the right CIA aneurysm in an end-to-side fashion to facilitate delivery of a Zenith endograft constructed with 2 small fenestrations for the renal arteries, 1 large strut-free fenestration for the superior mesenteric artery, and a scallop for the celiac trunk. The proximal fenestrated body of the Zenith device was introduced via the right iliac artery by direct puncture of the common femoral artery. The conduit was used to cannulate the 3 fenestrations for subsequent deployment and for delivery of the distal Zenith aortomonoiliac device. The procedure was completed successfully, but 12 hours after surgery, the patient developed a significant right retroperitoneal hematoma, which was treated surgically. CT confirmed patency of all visceral arteries and no endoleak. One month after the initial procedure, he had recovered totally and was discharged. CONCLUSION: Iliac conduits could widen the feasibility of fenestrated endografting in patients unfit for open surgery with pararenal aneurysms and challenging iliac anatomy. However, this adjunctive procedure has its own morbidity. PMID- 17723013 TI - Hybrid thoracoabdominal aneurysm repair with simultaneous antegrade visceral revascularization and supra-aortic debranching from the ascending aorta. AB - PURPOSE: To describe a hybrid technique involving combined antegrade revascularization of both supra-aortic and visceral arteries and complete exclusion of a dissecting thoracoabdominal aortic aneurysm (TAAA). TECHNIQUE: A 46-year-old man had a dissecting TAAA involving the left subclavian artery (LSA) and the descending thoracic and abdominal aorta down to the left common iliac artery. The ascending aorta was the only feasible source of inflow to the cerebral and visceral vessels. Via a median thoracolaparotomy, the supra-aortic and visceral arteries were dissected, and an octopus graft was implanted using 3 bifurcated Dacron grafts. An 18-x9-mm bifurcated Dacron graft was anastomosed in an end-to-side fashion to the ascending aorta, the brachiocephalic trunk, and the left common carotid artery. A 16-x8-mm bifurcated Dacron graft was sutured end-to side to the celiac artery and superior mesenteric artery. A third 12-x7-mm bifurcated graft was sutured to both renal arteries. In a second step, 3 tapered custom-made thoracic Zenith TX2 endografts were used to repair the thoracic and the thoracoabdominal aorta. A bifurcated Zenith AAA device was used to treat the aneurysm at the level of the infrarenal aorta and both iliac arteries. Despite covering the LSA and all intercostal and lumbar arteries, the patient developed only a temporary paresis of the left leg. Computed tomography showed complete exclusion of the aneurysm and normal flow to the supra-aortic and visceral arteries. CONCLUSION: In selected cases, this hybrid approach using the ascending aorta for antegrade revascularization of cerebral and visceral arteries is feasible, with acceptable perioperative morbidity. However, its role for the treatment of complex thoracoabdominal aortic disease must be evaluated further. PMID- 17723014 TI - Impact of diabetes, patient age, and gender on the 30-day incidence of stroke and death in patients undergoing carotid artery stenting with embolus protection: a post-hoc subanalysis of a prospective multicenter registry. AB - PURPOSE: To assess the impact of diabetes, patient age, and gender on major periprocedural (30-day) complications (major and minor strokes, all-cause deaths) following carotid artery stenting (CAS). METHODS: An exploratory analysis was performed of 695 patients (516 men; mean age 69.9+/-8.4 years) enrolled consecutively between September 1999 and September 2002 in a multicenter Italian/German registry of routine CAS using cerebral protection devices. There were 535 nondiabetic patients and 160 diabetic patients in the analysis. RESULTS: Logistic regression analysis revealed that diabetes and age, but not gender, impacted the cumulative 30-day incidence of any stroke and death (OR 2.1, 95% CI 1.0 to 4.8, p = 0.068 and OR 1.06, 95% CI 1.01 to 1.12, p = 0.031, respectively), as well as the 30-day incidence of major strokes and deaths (OR 5.9, 95% CI 1.6 to 21.8, p = 0.007 and OR 1.13, 95% CI 1.02 to 1.25, p = 0.018, respectively). According to receiver-operating characteristic analysis, age had no discriminatory power to predict complications in nondiabetic patients, but an age of 75 years was identified as the optimal cut point to predict complications in diabetic patients. Compared with nondiabetic patients, diabetics > or =75 years had a 4.3 greater risk of experiencing any stroke or death (95% CI 1.3 to 12.3, p = 0.016) and a 12.0 greater risk of a major stroke or death (95% CI 2.1 to 66.5, p = 0.005). Diabetics <75 years had no increase in risk over that of nondiabetic patients. CONCLUSION: Diabetic patients > or =75 years carry a significantly increased risk for strokes or death after protected CAS. The findings should be taken into consideration when treating elderly diabetic patients. PMID- 17723015 TI - Percutaneous interventions in patients with acute ischemic stroke related to obstructive atherosclerotic disease or dissection of the extracranial carotid artery. AB - PURPOSE: To determine the safety, feasibility, and efficacy of carotid artery stenting (CAS) in patients with acute stroke who underwent angioplasty of the extracranial internal carotid artery (ICA). METHODS: Patients were eligible for CAS if they presented within 6 hours of symptom onset and had a National Institutes of Health Stroke Scale (NIHSS) score >4. The records of all 18 acute stroke patients (11 men; mean age 68.3+/-14.3 years) who underwent endovascular intervention in the stroke-related extracranial ICA between May 2003 and February 2006 were reviewed. Fourteen (77.8%) had atheromatous obstructions and 4 (22.2%) had dissection of the extracranial ICA. Major adverse cerebral and cardiac events (MACCEs) and neurological status, including NIHSS and the modified Rankin Scale (mRS) scores, were recorded for all patients. RESULTS: Successful revascularization was achieved in 83.3% (15/18) of the patients. Cerebral protection devices were applied successfully in 13 (72.2%). At discharge, a neurological improvement (NIHSS reduction > or =4) was observed in 77.8% (14/18) of patients. The clinical success rate was 72.2% (13/18). The median NIHSS was 8.5 on admission versus 4.5 at discharge (p<0.01). The 30-day death and stroke rate was 11.1%. During the 14.6+/-9.3-month follow-up, the MACCE and the death/stroke rates were 33.3% and 27.8%, respectively. The median mRS scores at 30 days and at midterm follow-up were 1 and 2.5, respectively (p = NS). CONCLUSION: Endovascular revascularization of the extracranial ICA in patients with acute ischemic stroke is associated with high procedural success rates and favorable midterm outcome. PMID- 17723016 TI - Steno-occlusive carotid artery disease in the setting of acute ischemic stroke: to stent or not to stent? PMID- 17723017 TI - Retrievability of the Gunther Tulip vena cava filter after dwell times longer than 180 days in patients with multiple trauma. AB - PURPOSE: To evaluate the retrieval feasibility of the Gunther Tulip inferior vena cava filter (IVCF) after dwell times >180 days in patients with multiple trauma. METHODS: A retrospective study was conducted of 117 multiple-trauma patients (70 men; mean age 36 years, range 17 to 64) who underwent prophylactic placement of Gunther Tulip retrievable IVCFs between December 1, 2003 and October 1, 2006. Prior to IVCF retrieval, all patients had vena cavography to identify possible IVCF thrombus entrapment. Filter retrieval was performed in the catheterization laboratory under sterile conditions from a right internal jugular vein approach. After IVCF retrieval, repeat vena cavography was performed to evaluate the IVC for contrast extravasation, intraluminal defects, or IVC narrowing. RESULTS: Twelve (10.3%) filters were not retrieved as the patients died of their injuries (no deaths related to IVCF placement or retrieval). Forty-one (35.0%) filters had dwell times >180 days (mean 261.5 days, range 182-403). Of these, 31 (76%) were uneventfully retrieved; 10 were left in place permanently. Pre-retrieval vena cavography identified filter tilting in 13 filters: 9 had a mild tilt < or =10 degrees, and 4 had severe tilting > or =25 degrees. All of the 10 filters that could not be retrieved were tilted (4 severe and 6 mild). In comparison to the 64 (54.7%) filters in place for <180 days (mean 51 days, range 42-180), 4 (6.2%) could not be retrieved (p = 0.367). No filter had trapped thrombus identified by vena cavography at the time of retrieval. None of the retrieved filters had structural fracture or collapse, and none had migrated. Post-retrieval vena cavograms demonstrated no contrast extravasation, intraluminal defects, or impingement on adjacent organs. CONCLUSION: If retrieval of a Gunther Tulip filter with an dwell time >180 days is considered, the patient should be ambulatory and a candidate for anticoagulation if indicated; notably, the filter should have a <25 degrees tilt. Under these circumstances, retrieval of the Gunther Tulip filter after 180 days of dwell time appears justified and safe. PMID- 17723018 TI - Initial experience with directed laser atherectomy using the CLiRpath photoablation atherectomy system and bias sheath in superficial femoral artery lesions. AB - PURPOSE: To report a safety and efficacy study of directed excimer laser atherectomy with the Bias Sheath guiding catheter to create larger lumens in the superficial femoral artery (SFA). METHODS: Fourteen patients (9 men; mean age 66+/-9 years, range 46-76) with chronic lower limb ischemia (Rutherford class 2 to 5) referable to SFA stenoses were treated with the 8-F-compatible Bias Sheath and a 1.7- or 2.0-mm laser catheter. Eight (57%) lesions were de novo and 6 (43%) were in-stent restenoses (ISR). Mean diameter stenosis was 96%+/-8% (range 80% 100%; 10 total occlusions), and mean lesion length was 126+/-78 mm (range 30 290). The primary study endpoint was laser success, defined as <50% angiographic residual stenosis post-laser, without major perforations. RESULTS: The primary endpoint was achieved in 8 (57%) lesions; all patients underwent additional balloon angioplasty, which achieved an angiographic residual stenosis <30% in all. Three lesions could not be completely traversed with the study device. Two dissections were detected after Bias Sheath application; 1 required stenting. There were 2 embolic events (specific to the antegrade device design); both were treated with aspiration therapy. Intravascular ultrasound (IVUS)-based minimal lumen diameters were 0.23+/-0.2 mm (range 0-1.0) at baseline and 3.2+/-0.8 mm after Bias Sheath application. Rutherford category improved at 1 month in 10 (71%) patients. One patient remained unchanged, another worsened (category 2 to 3), 1 died, and the fourth was not examined. The ankle-brachial index improved from 0.41+/-0.18 at baseline to 0.79+/-0.19 at discharge and to 0.80+/-0.19 at 1 month. Primary 1-month patency (<50% restenosis by duplex) was 85% (11/13 lesions). CONCLUSION: SFA lesions, including ISR, can be treated in the majority of cases with directed laser atherectomy, significantly reducing plaque burden as measured by IVUS. Embolization was attributed to device-specific features of the prototype antegrade sheath design, which was discontinued. Larger studies are mandatory to document the long-term technical and clinical impact of this new device. PMID- 17723019 TI - Angio-seal in antegrade endovascular interventions: technical success and complications in a 55-patient series. AB - PURPOSE: To assess the technical success and complications of Angio-Seal vascular closure device in antegrade common femoral artery (CFA) punctures. METHODS: Over a 14-month period, 55 patients (37 men; age range 37-94 years) underwent antegrade CFA Angio-Seal placement at a single center; the clinical data and angiograms were reviewed retrospectively. A total of 56 antegrade CFA punctures were made for hemostasis; 6-F Angio-Seal devices (40 model STS and 12 model VIP) were deployed in 52 CFAs, and 8-F Angio-Seal devices were deployed in 4. RESULTS: The technical success rate was 98.2% (55/56). Two (3.6%) patients developed small, non-expanding hematomas (<5 cm) during deployment of the device. There was 1 episode of device/operator failure, presumably due to extravascular deployment within soft tissue. None of the patients developed pseudoaneurysm, arterial injury, or large hematomas requiring transfusion. Small calcified plaques at the puncture site did not influence the outcome. CONCLUSION: This series suggests that Angio-Seal may be a safe and effective device for hemostasis in antegrade CFA punctures. Further randomized trials testing its risk-benefit balance in comparison to standard manual compression are warranted. PMID- 17723020 TI - Iliac arterial conduits for endovascular access: technical considerations. AB - PURPOSE: To describe the relevant technical details that have proved helpful in a 10-year experience using iliac access conduits. TECHNIQUES: Standard surgical techniques are used to achieve retroperitoneal exposure of the common iliac artery (CIA) via a relatively short oblique incision in the lower quadrant of the abdomen. On occasion, the distal abdominal aorta is the only reasonable or available target for anastomosis and conduit attachment. A left-side approach is preferred. A 10-mm-diameter Dacron graft is the best conduit because it provides enough luminal space for introduction of all delivery systems. The anastomosis is sewn end-to-side between the graft and the CIA using a running suture technique. After completion of the anastomosis, the conduit is exited through the abdominal wall via a small stab incision made just above the inguinal ligament, providing a smooth angle of entry that will facilitate introduction of the large devices to be passed through the conduit. Upon completion of the endovascular procedure, the iliac conduit is excised, leaving behind only a short stub that is carefully oversewn with a running propylene suture. After achieving perfect hemostasis, the incision is closed in layers using standard technique. CONCLUSION: Access challenges requiring an iliac conduit may also be overcome by direct puncture and repair of the CIA following retroperitoneal exposure, without attaching a conduit or retrograde endarterectomy via a femoral artery exposure, with or without subsequent relining with a covered stent. While such techniques may have merit, we continue to rely on the iliac conduit approach for all such cases. PMID- 17723021 TI - Early and midterm results after open and endovascular repair of ruptured abdominal aortic aneurysms in a comparative analysis. AB - PURPOSE: To compare early and midterm results of open versus endovascular aortic repair of ruptured abdominal aneurysms (rAAA). METHODS: A retrospective analysis was performed of 58 consecutive patients with rAAA who were treated with open or endovascular aneurysm repair (EVAR) at a single center between January 2000 and December 2005. Patients without definitive signs of rupture (symptomatic patients) were excluded from the study. Twenty-nine patients (21 men; median age 71 years) were treated using endovascular techniques (EVAR group) and 29 (28 men; median age 71 years) with open repair (OR group). The hemodynamic status at the time of admission was evaluated with respect to blood pressure, pulse rate, and hemoglobin level to reduce selection bias. Patients underwent follow-up by clinical examination and computed tomography. RESULTS: The 30-day mortality rate was 31% (9/29) in each group (p = 1.0); the morbidity rates also did not differ between groups [16 (55.2%) EVAR vs. 18 (62.1%) OR; p = 0.9]. There was 1 (3.4%) primary conversion in the EVAR group and 7 (24.1%) endoleaks [3 (10.3%) primary; 4 (13.8%) secondary]. There was no difference between the groups with regard to intensive care unit stay (4 days for EVAR vs. 3 days for OR, p = 0.98) or total hospital stay (9 days for EVAR vs. 12 days for OR, p = 0.69). After a mean follow up of 40.25 months (range 1-70), the midterm mortality rates did not differ [5 (17.2%) EVAR vs. 3 (10.3%) OR, p = 0.41]. CONCLUSION: EVAR of rAAAs is feasible, with equal early and midterm mortality rates compared to open repair. When a defined patient selection is used for rupture, including hemodynamic status, there is no evidence of a better outcome with EVAR in emergency cases. PMID- 17723022 TI - Successful treatment of cold-induced neck pain and jaw claudication with revascularization of severe atherosclerotic external carotid artery stenoses. AB - PURPOSE: To present a patient whose cold-triggered neck pain and jaw claudication remitted after revascularization of severe atherosclerotic stenoses of both external carotid arteries (ECA). CASE REPORT: A 60-year-old vintner presented with jaw claudication and neck pain that increased in severity while he worked in cold temperatures. Angiography showed severe atherosclerotic narrowing of both ECAs. The symptoms disappeared after staged, bilateral percutaneous transluminal angioplasty procedures. However, the pain recurred together with severe bilateral ECA restenoses 6 months later; once again, the pain remitted after redilation. Right-sided neck pain and severe ECA narrowing recurred 5 months later and resolved after carotid endarterectomy. The patient remained asymptomatic and showed no ECA stenosis during a 3-year follow-up. CONCLUSION: Cold-triggered neck pain may be a symptom of atherosclerotic ECA stenoses, and carotid revascularization may be an efficient and safe treatment. PMID- 17723024 TI - Treatment of a false visceral aneurysm with the Symbiot covered stent. PMID- 17723023 TI - Percutaneous rotational and aspiration atherectomy in infrainguinal peripheral arterial occlusive disease: a multicenter pilot study. AB - PURPOSE: To report a safety and efficacy study of the first rotational aspiration atherectomy system (Pathway PV) for the treatment of arterial lesions below the femoral bifurcation. METHODS: From December 2005 to February 2006, 15 patients (9 men; mean age 71+/-9 years) with Rutherford stage 2 to 5 lower limb ischemia were enrolled at 3 study sites. Target lesions were in the superficial femoral (n = 7, 47%), popliteal (n = 7, 47%), and posterior tibial (n = 1, 6%) arteries. Mean diameter stenosis was 97%+/-10%; mean lesion length was 61+/-62 mm (range 5-250). The primary study endpoint was the 30-day serious adverse event (SAE) rate. RESULTS: Interventional success (residual stenosis <30%) was achieved in all lesions (100%). Stand alone atherectomy was performed in 6 (40%) patients, adjunctive balloon angioplasty in 7 (47%), and stenting/endografting in 2 (13%). The SAE rate at 30 days was 20% (3/15), including 1 perforation due to an unrecognized displacement of the guidewire (sealed with an endograft), 1 false aneurysm at the puncture site (successful duplex-guided compression therapy), and 1 dissection in conjunction with a distal embolism (stent implantation and aspiration thrombectomy). Primary patency rates measured by duplex ultrasound at 1 and 6 months were 100% and 73%, respectively; the TLR rate was 0% after 6 months. The ankle-brachial index increased significantly from 0.54+/-0.3 at baseline to 0.89+/-0.16, 0.88+/-0.19, and 0.81+/-0.20 (p<0.05) at discharge, 1 month, and 6 months, respectively. Mean Rutherford categories were 2.92+/-1.19 (range 1-5), 0.64+/-1.12 (range 0-1), and 0.83+/-1.33 (range 0-3) at the same time points (p<0.05). CONCLUSION: The application of this new atherectomy device was feasible in all cases. The serious adverse event rate was moderate; however, all events were solved during the index procedure. The 0% 6-month TLR rate is promising. PMID- 17723025 TI - Management of chronic mesenteric ischemia. The role of endovascular therapy. AB - Chronic mesenteric ischemia is an uncommon disorder manifested most commonly as abdominal pain. Surgical revascularization has traditionally been the treatment of choice. Endovascular management of this entity was originally attempted as an alternative for high-risk patients. Improvements in stent technology, refinement in technique, and increased efficiency of antiplatelet regimens have, over time, increased the popularity of this minimally invasive approach. We present a review of the available series on endovascular treatment of chronic mesenteric ischemia, with emphasis on short- and long-term outcome and morbidity and mortality results. Principles of operative technique and controversial issues and topics of interest are also discussed. PMID- 17723026 TI - Global collaborators on advanced stent-graft techniques for aneurysm repair (GLOBALSTAR) project. PMID- 17723027 TI - The psychophysiology of posttraumatic stress disorder: a meta-analysis. AB - This meta-analysis of 58 resting baseline studies, 25 startle studies, 17 standardized trauma cue studies, and 22 idiographic trauma cue studies compared adults with and without posttraumatic stress disorder (PTSD) on psychophysiological variables: facial electromyography (EMG), heart rate (HR), skin conductance (SC), and blood pressure. Significant weighted mean effects of PTSD were observed for HR (r = .18) and SC (r = .08) in resting baseline studies; eyeblink EMG (r = .13), HR (r = .23), and SC habituation slope (r = .21) in startle studies; HR (r = .27) in standardized trauma cue studies; and frontalis EMG (r = .21), corrugator EMG (r = .34), HR (r = .22), and SC (r = .19) in idiographic trauma cue studies. The most robust correlates of PTSD were SC habituation slope, facial EMG during idiographic trauma cues, and HR during all study types. Overall, the results support the view that PTSD is associated with elevated psychophysiology. However, the generalizability of these findings is limited by characteristics of the published literature, including its disproportionate focus on male veterans and neglect of potential PTSD subtypes. PMID- 17723028 TI - Vitamins, minerals, and mood. AB - In this article, the authors explore the breadth and depth of published research linking dietary vitamins and minerals (micronutrients) to mood. Since the 1920s, there have been many studies on individual vitamins (especially B vitamins and Vitamins C, D, and E), minerals (calcium, chromium, iron, magnesium, zinc, and selenium), and vitamin-like compounds (choline). Recent investigations with multi ingredient formulas are especially promising. However, without a reasonable conceptual framework for understanding mechanisms by which micronutrients might influence mood, the published literature is too readily dismissed. Consequently, 4 explanatory models are presented, suggesting that mood symptoms may be expressions of inborn errors of metabolism, manifestations of deficient methylation reactions, alterations of gene expression by nutrient deficiency, and/or long-latency deficiency diseases. These models provide possible explanations for why micronutrient supplementation could ameliorate some mental symptoms. PMID- 17723030 TI - Toward a neurophysiological theory of auditory stream segregation. AB - Auditory stream segregation (or streaming) is a phenomenon in which 2 or more repeating sounds differing in at least 1 acoustic attribute are perceived as 2 or more separate sound sources (i.e., streams). This article selectively reviews psychophysical and computational studies of streaming and comprehensively reviews more recent neurophysiological studies that have provided important insights into the mechanisms of streaming. On the basis of these studies, segregation of sounds is likely to occur beginning in the auditory periphery and continuing at least to primary auditory cortex for simple cues such as pure-tone frequency but at stages as high as secondary auditory cortex for more complex cues such as periodicity pitch. Attention-dependent and perception-dependent processes are likely to take place in primary or secondary auditory cortex and may also involve higher level areas outside of auditory cortex. Topographic maps of acoustic attributes, stimulus-specific suppression, and competition between representations are among the neurophysiological mechanisms that likely contribute to streaming. A framework for future research is proposed. PMID- 17723031 TI - Receiver operating characteristics (ROCs) in recognition memory: a review. AB - Receiver operating characteristic (ROC) analysis is being used increasingly to examine the memory processes underlying recognition memory. The authors discuss the methodological issues involved in conducting and analyzing ROC results, describe the various models that have been developed to account for these results, review the behavioral empirical literature, and assess the models in light of those results. The empirical literature includes studies of item recognition, relational recognition (e.g., source and associative tests), as well as exclusion and remember-know tasks. Nine empirical regularities are described, and a number of unresolved empirical issues are identified. The results indicate that several common classes of recognition models, such as pure threshold and pure signal detection models, are inadequate to account for recognition memory, whereas several hybrid models that incorporate a signal detection-based process and a threshold recollection or attention process are in better agreement with the results. The results indicate that there are at least 2 functionally distinct component/processes underlying recognition memory. In addition, the ROC results have various implications for how recognition memory performance should be measured. PMID- 17723029 TI - Retrieval of emotional memories. AB - Long-term memories are influenced by the emotion experienced during learning as well as by the emotion experienced during memory retrieval. The present article reviews the literature addressing the effects of emotion on retrieval, focusing on the cognitive and neurological mechanisms that have been revealed. The reviewed research suggests that the amygdala, in combination with the hippocampus and prefrontal cortex, plays an important role in the retrieval of memories for emotional events. The neural regions necessary for online emotional processing also influence emotional memory retrieval, perhaps through the reexperience of emotion during the retrieval process. PMID- 17723032 TI - Neuropsychological impairments in schizophrenia: Integration of performance-based and brain imaging findings. AB - Until recently, the dominant view was that schizophrenia patients have limited, if any, neuropsychological impairments, and those that are observed are only secondary to the florid symptoms of the disorder. This view has dramatically changed. This review integrates recent evidence demonstrating the severity and profile of neuropsychological impairments in schizophrenia. We present quantitative evaluation of the literature demonstrating that the most severe impairments are apparent in episodic memory and executive control processes, evident on a background of a generalized cognitive deficit. The neuropsychological impairments potentially represent genetic liability to the disorder, as similar, yet milder, impairments are evident in schizophrenia patients even before the onset of psychotic symptoms, as well as in the nonpsychotic relatives of schizophrenia patients. Corresponding cognitive neuroimaging literature on executive functions, episodic memory, and working memory in schizophrenia documenting abnormalities in frontal and medial temporal lobes is summarized, and current models integrating neuropsychological and neuroimaging data are discussed. PMID- 17723033 TI - Sensitive questions in surveys. AB - Psychologists have worried about the distortions introduced into standardized personality measures by social desirability bias. Survey researchers have had similar concerns about the accuracy of survey reports about such topics as illicit drug use, abortion, and sexual behavior. The article reviews the research done by survey methodologists on reporting errors in surveys on sensitive topics, noting parallels and differences from the psychological literature on social desirability. The findings from the survey studies suggest that misreporting about sensitive topics is quite common and that it is largely situational. The extent of misreporting depends on whether the respondent has anything embarrassing to report and on design features of the survey. The survey evidence also indicates that misreporting on sensitive topics is a more or less motivated process in which respondents edit the information they report to avoid embarrassing themselves in the presence of an interviewer or to avoid repercussions from third parties. PMID- 17723035 TI - Young children associate novel words with complex objects rather than salient parts. AB - How do children learn associations between novel words and complex perceptual displays? Using a visual preference procedure, the authors tested 12- and 19 month-olds to see whether the infants would associate a novel word with a complex 2-part object or with either of that object's parts, both of which were potentially objects in their own right and 1 of which was highly salient to infants. At both ages, children's visual fixation times during test were greater to the entire complex object than to the salient part (Experiment 1) or to the less salient part (Experiment 2)--when the original label was requested. Looking times to the objects were equal if a new label was requested or if neutral audio was used during training (Experiment 3). Thus, from 12 months of age, infants associate words with whole objects, even those that could potentially be construed as 2 separate objects and even if 1 of the parts is salient. PMID- 17723037 TI - Children's differentiation between beliefs about matters of fact and matters of opinion. AB - Two experiments investigated children's implicit and explicit differentiation between beliefs about matters of fact and matters of opinion. In Experiment 1, 8- to 9-year-olds' (n = 88) explicit understanding of the subjectivity of opinions was found to be limited, but their conformity to others' judgments on a matter of opinion was considerably lower than their conformity to others' views regarding an ambiguous fact. In Experiment 2, children aged 6, 8, or 10 years (n = 81) were asked to make judgments either about ambiguous matters of fact or about matters of opinion and then heard an opposing judgment from an expert. All age groups conformed to the opposing judgments on factual matters more than they did to the experts' views on matters of opinion. However, only the oldest children explicitly recognized that opinions are subjective and cannot be "wrong." Implications of these results for models of children's reasoning about epistemic states are discussed. PMID- 17723036 TI - The varieties of speech to young children. AB - This article examines caregiver speech to young children. The authors obtained several measures of the speech used to children during early language development (14-30 months). For all measures, they found substantial variation across individuals and subgroups. Speech patterns vary with caregiver education, and the differences are maintained over time. While there are distinct levels of complexity for different caregivers, there is a common pattern of increase across age within the range that characterizes each educational group. Thus, caregiver speech exhibits both long-standing patterns of linguistic behavior and adjustment for the interlocutor. This information about the variability of speech by individual caregivers provides a framework for systematic study of the role of input in language acquisition. PMID- 17723039 TI - It's a sign of the kind: gestures and words guide infants' inductive inferences. AB - The role of words and gestures in guiding infants' inductive inferences about nonobvious properties was examined. One hundred seventy-two 14-month-olds and 22 month-olds were presented with novel target objects followed by test objects that varied in similarity to the target. Objects were introduced with a novel word or a novel gesture or with no label. When target and test objects were highly similar in shape, both 14- and 22-month-olds inferred that these objects shared a nonobvious property, regardless of whether the objects were labeled with a word or a gesture or with no label. When objects were labeled with the same word, both 14- and 22-month-olds generalized the nonobvious properties to objects that shared minimal perceptual similarity. Finally, when objects were labeled with the same gesture, 14-month-olds, but not 22-month-olds, generalized the nonobvious properties to objects that shared minimal perceptual similarity. These results indicate that 14-month-olds possess a more generalized symbolic system as they will rely on both words and gestures to guide their inferences. By 22-months of age, infants treat words as a privileged referential form when making inductive inferences. PMID- 17723040 TI - Can being scared cause tummy aches? Naive theories, ambiguous evidence, and preschoolers' causal inferences. AB - Causal learning requires integrating constraints provided by domain-specific theories with domain-general statistical learning. In order to investigate the interaction between these factors, the authors presented preschoolers with stories pitting their existing theories against statistical evidence. Each child heard 2 stories in which 2 candidate causes co-occurred with an effect. Evidence was presented in the form: AB?E; CA?E; AD?E; and so forth. In 1 story, all variables came from the same domain; in the other, the recurring candidate cause, A, came from a different domain (A was a psychological cause of a biological effect). After receiving this statistical evidence, children were asked to identify the cause of the effect on a new trial. Consistent with the predictions of a Bayesian model, all children were more likely to identify A as the cause within domains than across domains. Whereas 3.5-year-olds learned only from the within-domain evidence, 4- and 5-year-olds learned from the cross-domain evidence and were able to transfer their new expectations about psychosomatic causality to a novel task. PMID- 17723034 TI - Food reinforcement and eating: a multilevel analysis. AB - Eating represents a choice among many alternative behaviors. The purpose of this review is to provide an overview of how food reinforcement and behavioral choice theory are related to eating and to show how this theoretical approach may help organize research on eating from molecular genetics through treatment and prevention of obesity. Special emphasis is placed on how food reinforcement and behavioral choice theory are relevant to understanding excess energy intake and obesity and how they provide a framework for examining factors that may influence eating and are outside of those that may regulate energy homeostasis. Methods to measure food reinforcement are reviewed, along with factors that influence the reinforcing value of eating. Contributions of neuroscience and genetics to the study of food reinforcement are illustrated by using the example of dopamine. Implications of food reinforcement for obesity and positive energy balance are explored, with suggestions for novel approaches to obesity treatment based on the synthesis of behavioral and pharmacological approaches to food reinforcement. PMID- 17723038 TI - Socioeconomic status, schooling, and the developmental trajectories of adolescents. AB - The socioeconomic stratification of American society profoundly influences how the life course unfolds by shaping various developmental pathways as well as the connections among these pathways. Drawing on a nationally representative sample of American adolescents, this study charted trajectories of personal control and parental consultation from middle school to the end of high school and then examined how various combinations of these trajectories were associated with math/science course taking in high school across socioeconomic strata. Results indicated that low and/or decreasing levels of personal control were associated with the accumulation of fewer math/science credits, as were declining levels of parental consultation no matter what the initial level. Mismatches between control and consultation trajectories (e.g., high, stable control with low, stable consultation) were also associated with fewer math/science credits. These patterns tended to be less predictive of math/science credit accumulation at the highest and lowest ends of the socioeconomic spectrum. PMID- 17723041 TI - Maternal employment and child cognitive outcomes: the importance of analytic approach. AB - J. Brooks-Gunn, W. J. Han, and J. Waldfogel (2002) and the National Institute of Child Health and Human Development Early Child Care Research Network (ECCRN; 2000b) came to different conclusions about the effects of maternal employment- although they were addressing similar questions using the same data set. Brooks Gunn et al. concluded that maternal employment in infancy has a negative effect on children's cognitive abilities at age 3, whereas the ECCRN found that early nonmaternal care is not related to children's cognitive abilities in their first 3 years. The authors account for this difference by comparing 2 approaches to data analysis: a top-down testing of continuous variables (the approach used by the ECCRN, 2000b) and an a priori comparison approach that involves pairwise testing of specific dichotomous contrasts (the approach used by Brooks-Gunn et al., 2002). This comparison illustrates the critical importance of analytic approach. It also suggests that Brooks-Gunn et al.'s conclusion from this data set is overstated and should not be used on its own as the basis for practical or policy decisions. PMID- 17723042 TI - Language access and theory of mind reasoning: evidence from deaf children in bilingual and oralist environments. AB - This investigation examined whether access to sign language as a medium for instruction influences theory of mind (ToM) reasoning in deaf children with similar home language environments. Experiment 1 involved 97 deaf Italian children ages 4-12 years: 56 were from deaf families and had LIS (Italian Sign Language) as their native language, and 41 had acquired LIS as late signers following contact with signers outside their hearing families. Children receiving bimodal/bilingual instruction in LIS together with Sign-Supported and spoken Italian significantly outperformed children in oralist schools in which communication was in Italian and often relied on lipreading. Experiment 2 involved 61 deaf children in Estonia and Sweden ages 6-16 years. On a wide variety of ToM tasks, bilingually instructed native signers in Estonian Sign Language and spoken Estonian succeeded at a level similar to age-matched hearing children. They outperformed bilingually instructed late signers and native signers attending oralist schools. Particularly for native signers, access to sign language in a bilingual environment may facilitate conversational exchanges that promote the expression of ToM by enabling children to monitor others' mental states effectively. PMID- 17723043 TI - Relations of maternal socialization and toddlers' effortful control to children's adjustment and social competence. AB - The authors examined the relations of maternal supportive parenting to effortful control and internalizing problems (i.e., separation distress, inhibition to novelty), externalizing problems, and social competence when toddlers were 18 months old (n = 256) and a year later (n = 230). Mothers completed the Coping With Toddlers' Negative Emotions Scale, and their sensitivity and warmth were observed. Toddlers' effortful control was measured with a delay task and adults' reports (Early Childhood Behavior Questionnaire). Toddlers' social functioning was assessed with the Infant/Toddler Social and Emotional Assessment. Within each age, children's regulation significantly mediated the relation between supportive parenting and low levels of externalizing problems and separation distress, and high social competence. When using stronger tests of mediation, controlling for stability over time, the authors found only partial evidence for mediation. The findings suggest these relations may be set at an early age. PMID- 17723045 TI - Trajectories of maternal depressive symptoms, maternal sensitivity, and children's functioning at school entry. AB - Using data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development, the authors modeled trajectories of maternal depressive symptoms from infant age 1 month to 7 years. The authors identified 6 trajectories of maternal depressive symptoms: high-chronic, moderate increasing, high-decreasing, intermittent, moderate-stable, and low-stable. Women on these depression trajectories varied in sociodemographic risk and in changes in observed maternal sensitivity over time. Maternal sensitivity was generally higher and increased when depressive symptoms were low; sensitivity was lower and decreased when depressive symptoms were either high or increasing. Child outcomes at 1st grade were examined by trajectory group. The authors discuss the complexity of disentangling maternal symptoms from maternal sensitivity and sociodemographic risk when predicting children's functioning. PMID- 17723044 TI - A conceptual model for the development of externalizing behavior problems among kindergarten children of alcoholic families: role of parenting and children's self-regulation. AB - The purpose of this study was to test a conceptual model predicting children's externalizing behavior problems in kindergarten in a sample of children with alcoholic (n = 130) and nonalcoholic (n = 97) parents. The model examined the role of parents' alcohol diagnoses, depression, and antisocial behavior at 12-18 months of child age in predicting parental warmth/sensitivity at 2 years of child age. Parental warmth/sensitivity at 2 years was hypothesized to predict children's self-regulation at 3 years (effortful control and internalization of rules), which in turn was expected to predict externalizing behavior problems in kindergarten. Structural equation modeling was largely supportive of this conceptual model. Fathers' alcohol diagnosis at 12-18 months was associated with lower maternal and paternal warmth/sensitivity at 2 years. Lower maternal warmth/sensitivity was longitudinally predictive of lower child self-regulation at 3 years, which in turn was longitudinally predictive of higher externalizing behavior problems in kindergarten, after controlling for prior behavior problems. There was a direct association between parents' depression and children's externalizing behavior problems. Results indicate that one pathway to higher externalizing behavior problems among children of alcoholics may be via parenting and self-regulation in the toddler to preschool years. PMID- 17723046 TI - Preschoolers monitor the relative accuracy of informants. AB - In 2 studies, the sensitivity of 3- and 4-year-olds to the previous accuracy of informants was assessed. Children viewed films in which 2 informants labeled familiar objects with differential accuracy (across the 2 experiments, children were exposed to the following rates of accuracy by the more and less accurate informants, respectively: 100% vs. 0%, 100% vs. 25%, 75% vs. 0%, and 75% vs. 25%). Next, children watched films in which the same 2 informants provided conflicting novel labels for unfamiliar objects. Children were asked to indicate which of the 2 labels was associated with each object. Three-year-olds trusted the more accurate informant only in conditions in which 1 of the 2 informants had been 100% accurate, whereas 4-year-olds trusted the more accurate informant in all conditions tested. These results suggest that 3-year-olds mistrust informants who make a single error, whereas 4-year-olds track the relative frequency of errors when deciding whom to trust. PMID- 17723047 TI - Do 9-month-old infants expect distinct words to refer to kinds? AB - In 3 experiments, 9-month-old infants' expectations for what distinct count noun labels refer to were investigated. In Experiment 1, a box was opened to reveal 2 objects inside during familiarization: either 2 identical objects or 2 different objects. Test trials followed the same procedure, except before the box was opened, the contents were described using 2 distinct labels ("I see a wug! I see a dak!") or the same label twice ("I see a zav! I see a zav!"). Infants who heard a label repeated twice looked longer at 2 different objects versus 2 identical objects, whereas infants who heard 2 distinct labels showed a different pattern of looking. Experiments 2 and 3 presented infants with object pairs that only differed in shape or color, and it was found that infants expected the different shaped (but not the different-colored) objects to be labeled by distinct count nouns. Because the property of shape is a cue to kind membership and the property of color is not, these results suggest that even at the beginning of word learning, infants may expect distinct labels to refer to distinct kinds of objects. PMID- 17723048 TI - European American and Chinese parents' responses to children's success and failure: implications for children's responses. AB - The authors examined cultural differences in parents' responses to their children's performance. In Study 1 (N = 421), Chinese 5th graders reported that their parents de-emphasized their academic success and emphasized their academic failure, whereas their American counterparts reported that their parents did the opposite. This partially accounted for Chinese (vs. American) children responding less positively to success and more negatively to failure. In Study 2 (N = 128), Chinese and American mothers' responses to their 4th and 5th graders' performance were observed in the laboratory. The cultural differences in children's reports of parents' responses documented in Study 1 were replicated; mothers' responses were also associated with children's subsequent performance. In addition, Chinese mothers were more involved than were American mothers, but their affect was similar. Taken together, the results suggest that parents' responses to children's performance may be a channel for cultural transmission and perpetuation of responses to performance. PMID- 17723049 TI - This cat has nine lives? Children's memory for genericity in language. AB - Generic noun phrases ("Birds lay eggs") are important for expressing knowledge about abstract kinds. The authors hypothesized that genericity would be part of gist memory, such that young children would appropriately recall whether sentences were presented as generic or specific. In 4 experiments, preschoolers and college students (N = 280) heard a series of sentences in either generic form (e.g., "Bears climb trees") or specific form (e.g., "This bear climbs trees") and were asked to recall the sentences following a 4-min distractor task. Participants in all age groups correctly distinguished between generic and specific noun phrases (NPs) in their recall, even when forgetting the details of the NP form. Memory for predicate content (e.g., "climb trees") was largely unaffected by genericity, although memory for category labels (e.g., "bear") was at times better for those who heard sentences with generic wording. Overall, these results suggest that generic form is maintained in long-term memory even for young children and thus may serve as the foundation for constructing knowledge about kinds. PMID- 17723050 TI - Children do show negative priming: further evidence for early development of an intact selective control mechanism. AB - Reactions to stimuli that were shortly before presented as distractors are usually slowed down; this phenomenon is known as negative priming. Negative priming is an accepted index for tapping into selective control mechanisms. Although this effect is well established for adults, it has been claimed that children do not show negative priming. Recently, however, V. E. Pritchard and E. Neumann challenged this view and concluded that selective control mechanisms are already fully developed in young children. The authors of the present study analyzed differences between older studies, in which no negative priming had been observed, and the Pritchard and Neumann (2004) study. In sum, the present study yielded further evidence for an intact selective control mechanism in young children. The authors also linked this empirical finding to the broader literature on negative priming by a direct comparison with an adult sample. PMID- 17723051 TI - Swagger, sway, and sexuality: Judging sexual orientation from body motion and morphology. AB - People can accurately judge the sexual orientation of others, but the cues they use have remained elusive. In 3 studies, the authors examined how body shape and motion affect perceived sexual orientation. In 2 studies, participants judged the sexual orientation of computer-generated animations in which body shape and motion were manipulated. Gender-typical combinations (e.g., tubular body moving with shoulder swagger or hourglass body moving with hip sway) were perceived generally to be heterosexual; gender-atypical combinations were perceived generally to be homosexual. These effects were stronger for male targets. Body shape affected perceived sexual orientation of women, but motion affected perceived sexual orientation of both men and women. Study 3 replicated and extended these findings. Participants judged dynamic outlines of real people (men and women, both gay and straight) in which body shape and motion were measured. Again, gender-atypical body motion affected perceived sexual orientation and, importantly, affected accuracy as well. PMID- 17723052 TI - Applying the attractor field model to social cognition: Perceptual discrimination is facilitated, but memory is impaired for faces displaying evaluatively congruent expressions. AB - A new model of mental representation is applied to social cognition: the attractor field model. Using the model, the authors predicted and found a perceptual advantage but a memory disadvantage for faces displaying evaluatively congruent expressions. In Experiment 1, participants completed a same/different perceptual discrimination task involving morphed pairs of angry-to-happy Black and White faces. Pairs of faces displaying evaluatively incongruent expressions (i.e., happy Black, angry White) were more likely to be labeled as similar and were less likely to be accurately discriminated from one another than faces displaying evaluatively congruent expressions (i.e., angry Black, happy White). Experiment 2 replicated this finding and showed that objective discriminability of stimuli moderated the impact of attractor field effects on perceptual discrimination accuracy. In Experiment 3, participants completed a recognition task for angry and happy Black and White faces. Consistent with the attractor field model, memory accuracy was better for faces displaying evaluatively incongruent expressions. Theoretical and practical implications of these findings are discussed. PMID- 17723053 TI - Process components of the Implicit Association Test: a diffusion-model analysis. AB - The authors present a diffusion-model analysis of the Implicit Association Test (IAT). In Study 1, the IAT effect was decomposed into 3 dissociable components: Relative to the compatible phase, (a) ease and speed of information accumulation are lowered in the incompatible phase, (b) more cautious speed-accuracy settings are adopted, and (c) nondecision components of processing require more time. Studies 2 and 3 assessed the nature of interindividual differences in these components. Construct-specific variance in the IAT relating to the construct to be measured (such as implicit attitudes) was concentrated in the compatibility effect on information accumulation (Studies 2 and 3), whereas systematic method variance in the IAT was mapped on differential speed-accuracy settings (Study 3). Implications of these dissociations for process theories of the IAT and for applications are discussed. PMID- 17723054 TI - Reducing explicit and implicit outgroup prejudice via direct and extended contact: The mediating role of self-disclosure and intergroup anxiety. AB - In 4 studies, the authors investigated mediators of the effect of cross-group friendship. In Study 1, cross-group friendship among White elementary school children predicted more positive explicit outgroup attitude toward South Asians, mediated by self-disclosure and intergroup anxiety. In Study 2, cross-group friendship and extended contact among White and South Asian high school students positively predicted explicit outgroup attitude, mediated by self-disclosure and intergroup anxiety. Study 3 replicated these findings in a larger independent sample. In all 3 studies, exposure to the outgroup positively predicted implicit outgroup attitude. Study 4 further showed that self-disclosure improved explicit outgroup attitude via empathy, importance of contact, and intergroup trust. The authors discuss the theoretical and practical implications of these findings, which argue for the inclusion of self-disclosure as a key component of social interventions to reduce prejudice. PMID- 17723055 TI - Can't take my eyes off you: Attentional adhesion to mates and rivals. AB - In 3 experiments, mating primes interacted with functionally relevant individual differences to guide basic, lower order social perception. A visual cuing method assessed biases in attentional adhesion--a tendency to have one's attention captured by particular social stimuli. Mate-search primes increased attentional adhesion to physically attractive members of the opposite sex (potential mates) among participants with an unrestricted sociosexual orientation but not among sexually restricted participants (Studies 1 and 2). A mate-guarding prime increased attentional adhesion to physically attractive members of one's own sex (potential rivals) among participants who were concerned with threats posed by intrasexual competitors but not among those less concerned about such threats (Study 3). Findings are consistent with a functionalist approach to motivation and social cognition and highlight the utility of integrating evolutionary and social cognitive perspectives. PMID- 17723056 TI - An unconscious desire for hierarchy? The motivated perception of dominance complementarity in task partners. AB - In 6 studies, the authors examined the perception of dominance complementarity, which is the perception of a target as different from the self in terms of dominance. The authors argue that these perceptions are motivated by the desire for positive task relationships. Because dominance complementarity bodes well for task-oriented relationships, seeing dominance complementarity allows one to be optimistic about a work relationship. As evidence that perceptions of dominance complementarity are an instance of motivated perception, the authors show that complementary perceptions occur when participants think about or expect task oriented relationships with the target and that perceptions of dominance complementarity are enhanced when individuals care about the task component of the relationship. PMID- 17723057 TI - Bridging the partisan divide: Self-affirmation reduces ideological closed mindedness and inflexibility in negotiation. AB - Three studies link resistance to probative information and intransigence in negotiation to concerns of identity maintenance. Each shows that affirmations of personal integrity (vs. nonaffirmation or threat) can reduce resistance and intransigence but that this effect occurs only when individuals' partisan identity and/or identity-related convictions are made salient. Affirmation made participants' assessment of a report critical of U.S. foreign policy less dependent on their political views, but only when the identity relevance of the issue rather than the goal of rationality was salient (Study 1). Affirmation increased concession making in a negotiation over abortion policy, but again this effect was moderated by identity salience (Studies 2 and 3). Indeed, although affirmed negotiators proved relatively more open to compromise when either the salience of their true convictions or the importance of remaining faithful to those convictions was heightened, the reverse was true when the salient goal was compromise. The theoretical and applied significance of these findings are discussed. PMID- 17723058 TI - Can emotions be truly group level? Evidence regarding four conceptual criteria. AB - Recent advances in understanding prejudice and intergroup behavior have made clear that emotions help explain people's reactions to social groups and their members. Intergroup emotions theory (D. M. Mackie, T. Devos, & E. R. Smith, 2000; E. R. Smith, 1993) holds that intergroup emotions are experienced by individuals when they identify with a social group, making the group part of the psychological self. What differentiates such group-level emotions from emotions that occur purely at the individual level? The authors argue that 4 key criteria define group-level emotions: Group emotions are distinct from the same person's individual-level emotions, depend on the person's degree of group identification, are socially shared within a group, and contribute to regulating intragroup and intergroup attitudes and behavior. Evidence from 2 studies supports all 4 of these predictions and thus points to the meaningfulness, coherence, and functionality of group-level emotions. PMID- 17723059 TI - Can I count on you to be there for me? Individual differences in a knowledge structure. AB - In Study 1, the authors applied the prototype methodology to identify indicators that people use to predict whether a potential partner will "be there" for them at future times of stress. Using these indicators, the authors constructed a new type of measure of individual differences, the Knowledge of Indicators (KNOWI) Scale. It assesses knowledge of indicators that lead to an expectation that a partner will be there when needed. This measure applies signal detection methods to assess each participant's ability to discriminate good from poor indicators. Two studies showed that the KNOWI Scale predicts performance on two laboratory tasks. In Study 2, participants interacted with a confederate who described a problem revealing subtle cues that another person will not be there when needed. High-scoring participants on the KNOWI Scale recognized the cues more readily. In Study 3, participants read stories about spouses that portrayed a "secure base script." They then read stories about the interaction of inanimate objects and judged which story best matched the human story. High-scoring participants on the KNOWI Scale made more correct matches. In Study 4, the KNOWI Scale was shown to possess convergent and discriminant validity. PMID- 17723060 TI - Working models of attachment and reactions to different forms of caregiving from romantic partners. AB - Inspired by attachment theory, the authors tested a series of theoretically derived predictions about connections between attachment working models (attachment to one's parents assessed by the Adult Attachment Interview; M. Main & R. Goldwyn, 1994) and the effectiveness of specific types of caregiving spontaneously displayed by dating partners during a stressful conflict-resolution discussion. Each partner first completed the Adult Attachment Interview. One week later, each couple was videotaped while they tried to resolve a current problem in their relationship. Trained observers then rated each interaction for the degree to which (a) emotional, instrumental, and physical caregiving behaviors were displayed; (b) care recipients appeared calmed by their partners' caregiving attempts; and (c) each partner appeared distressed during the discussion. Individuals who had more secure representations of their parents were rated as being more calmed if/when their partners provided greater emotional care, especially if they were rated as more distressed. Conversely, individuals who had more insecure (dismissive) representations of their parents reacted more favorably to instrumental caregiving behaviors from their partners, especially if they were more distressed. The broader theoretical implications of these findings are discussed. PMID- 17723061 TI - Culture and self-concept stability: consistency across and within contexts among Asian Americans and European Americans. AB - Whereas prior cultural research has focused on consistency of self-descriptions across contexts, the current 4 studies examined cultural differences in consistency of multiple self-dimensions and did so both across and within different contexts. Supporting predictions, Study 1a found that Asian Americans were less consistent in their self-descriptions across relationship contexts than were European Americans. Yet Study 1b, a short-term longitudinal study, found that Asian Americans' self-descriptions nonetheless showed high consistency within these contexts over time. Together, these findings suggest that for Asian Americans self-concept stability derives from defining the self in "if-then" terms, that is, as variable across relationship contexts but stable within them. In Studies 2a and 2b, parallel consistency effects emerged for 2 core motivational facets of the self-concept: self-view importance and self enhancement. Moreover, dialectical beliefs mediated the cultural difference in consistency across contexts. Overall, the results demonstrate both the robustness and the boundaries of cultural differences in self-concept consistency as well as the importance of examining multiple forms of stability in the self-concept. Implications for authenticity and well-being are discussed. PMID- 17723062 TI - Interpreting visual preferences in the visual paired-comparison task. AB - Performance on the visual paired-comparison (VPC) task has typically been interpreted with E. Sokolov's (1963) comparator model of the orienting response; novelty preferences are interpreted as evidence of retention, whereas null preferences are interpreted as evidence of forgetting. Here the authors capitalized on the verbal nature of human adults to clarify the interpretation of visual preferences in VPC performance. In 2 experiments, adults were tested on either the VPC task or a forced-choice recognition task after delays of 3 min to 12 months. In Experiment 1, adults tested on the VPC task exhibited novelty preferences after short delays, null preferences after intermediate delays, and familiarity preferences after long delays. In Experiment 2, adults tested on the forced-choice recognition task exhibited high levels of accuracy irrespective of delay, but the latency with which they recognized the stimuli increased systematically over the retention interval. These data are inconsistent with a simple Sokolovian interpretation of VPC performance and instead suggest that memory may be expressed as a novelty preference, null preference, or familiarity preference depending on the accessibility of the representation. PMID- 17723063 TI - When is an odd number not odd? Influence of task rule on the MARC effect for numeric classification. AB - When classifying numbers as odd or even with left-right keypresses, performance is better with the mapping even-right/odd-left than with the opposite mapping. This linguistic markedness association of response codes (MARC) effect has been attributed to compatibility between the linguistic markedness of stimulus and response codes. In 2 experiments participants made keypresses to the Arabic numerals or number words 3, 4, 8, and 9 using the odd-even parity rule or a multiple-of-3 rule, which yield the same keypress response for each stimulus. For both stimulus modes, the MARC effect was obtained with the odd-even rule, but tended to reverse with the multiple-of-3 rule. The reversal was complete for the right response, but task rule had little influence on the left response. The results are consistent with the view that the MARC effect and its reversal are caused by correspondence of the stimulus code designated as positive by the task rule with the positive-polarity right response code. PMID- 17723064 TI - Component processes of conceptual priming and associative cued recall: the roles of preexisting representation and depth of processing. AB - The authors investigated depth-of-processing effects on conceptual priming by comparing incidental (implicit) and intentional (explicit) tests of word association. In Experiment 1, depth of processing at study influenced priming of weak and medium associates but not of strong associates. In Experiment 2, depth of processing influenced priming of weak associates but not of compound phrases (e.g., coathanger), whose preexperimental association strength matched that of weak associates. In Experiment 3, the same pattern persisted when study was auditory and test was visual, ensuring that priming was conceptual and not perceptual. In all experiments, in matched intentional tests, depth-of-processing effects occurred for all association strengths and for both phrases and associates, suggesting that the incidental tests were uncontaminated by voluntary retrieval, because they showed depth-of-processing effects only for some materials and not others, within the same participants and tests. Because depth of-processing effects on involuntary free-association priming depend on the presence versus absence of a cohesive preexperimental representation, the memory systems and conceptual/perceptual processing approaches to memory-test dissociations require modification to account for component processes of conceptual priming. PMID- 17723065 TI - Retrieval-induced forgetting in item recognition: evidence for a reduction in general memory strength. AB - Retrieving a subset of previously studied material can impair later recognition of related items. Using the remember-know procedure (Experiment 1) and the receiver operating characteristic procedure (Experiment 2), the authors examined how such retrieval-induced forgetting can be explained in terms of single-process and dual-process accounts of recognition memory. Consistent across the 2 experiments, dual-process analysis suggested that retrieval practice reduces unpracticed items' familiarity but leaves their recollection largely unaffected, a finding that disagrees with prior work that points to recollective deficits in the forgotten items. Assuming that recognition is entirely based on a single source of memorial information, single-process analysis led to an excellent description of the data and suggested that retrieval practice reduces unpracticed items' general memory strength. This suggestion is consistent with prior work on free recall, cued recall, associative recognition, and response latencies and agrees with the inhibitory account of retrieval-induced forgetting. The authors argue that retrieval-induced forgetting in item recognition is caused by a reduction in general memory strength. PMID- 17723066 TI - The influence of open goals on the acquisition of problem-relevant information. AB - There have been a number of recent findings indicating that unsolved problems, or open goals more generally, influence cognition even when the current task has no relation to the task in which the goal was originally set. It was hypothesized that open goals would influence what information entered the problem-solving process. Three studies were conducted to establish the effect of open goals on the acquisition of problem-relevant information. It was found that problem relevant information, or hints, presented implicitly in a 2nd task in between attempts at solving problems aided problem solving. This effect cannot be attributed to strategic behavior after participants caught on to the manipulation, as most participants were not aware of the relationship. The implications of this research are discussed, including potential contributions to our understanding of insight, incubation, transfer, and creativity. PMID- 17723067 TI - Cue-independent task-specific representations in task switching: evidence from backward inhibition. AB - The compound-cue model of cognitive control in task switching explains switch cost in terms of a switch of task cues rather than of a switch of tasks. The present study asked whether the model generalizes to Lag 2 repetition cost (also known as backward inhibition), a related effect in which the switch from B to A in ABA task sequences is costlier than is the same switch in CBA task sequences. The model suggests that Lag 2 repetition cost should be absent from A'BA task sequences, in which A' and A are different cues for the same task. The cost is robust on such sequences, which suggests that cue-independent, task-specific representations are necessary for explaining task-switching performance and that the compound-cue model has limited explanatory power. PMID- 17723068 TI - Influences of spoken word planning on speech recognition. AB - In 4 chronometric experiments, influences of spoken word planning on speech recognition were examined. Participants were shown pictures while hearing a tone or a spoken word presented shortly after picture onset. When a spoken word was presented, participants indicated whether it contained a prespecified phoneme. When the tone was presented, they indicated whether the picture name contained the phoneme (Experiment 1) or they named the picture (Experiment 2). Phoneme monitoring latencies for the spoken words were shorter when the picture name contained the prespecified phoneme compared with when it did not. Priming of phoneme monitoring was also obtained when the phoneme was part of spoken nonwords (Experiment 3). However, no priming of phoneme monitoring was obtained when the pictures required no response in the experiment, regardless of monitoring latency (Experiment 4). These results provide evidence that an internal phonological pathway runs from spoken word planning to speech recognition and that active phonological encoding is a precondition for engaging the pathway. PMID- 17723069 TI - If you say thee uh you are describing something hard: the on-line attribution of disfluency during reference comprehension. AB - Eye-tracking and gating experiments examined reference comprehension with fluent (Click on the red. . .) and disfluent (Click on [pause] thee uh red . . .) instructions while listeners viewed displays with 2 familiar (e.g., ice cream cones) and 2 unfamiliar objects (e.g., squiggly shapes). Disfluent instructions made unfamiliar objects more expected, which influenced listeners' on-line hypotheses from the onset of the color word. The unfamiliarity bias was sharply reduced by instructions that the speaker had object agnosia, and thus difficulty naming familiar objects (Experiment 2), but was not affected by intermittent sources of speaker distraction (beeps and construction noises; Experiments 3). The authors conclude that listeners can make situation-specific inferences about likely sources of disfluency, but there are some limitations to these attributions. PMID- 17723070 TI - Shared syntactic representations in bilinguals: Evidence for the role of word order repetition. AB - Studies on syntactic priming strongly suggest that bilinguals can store a single integrated representation of constructions that are similar in both languages (e.g., Spanish and English passives; R. J. Hartsuiker, M. J. Pickering, & E. Veltkamp, 2004). However, they may store 2 separate representations of constructions that involve different word orders (e.g., German and English passives; H. Loebell & K. Bock, 2003). In 5 experiments, the authors investigated within--and between--languages priming of Dutch, English, and German relative clauses. The authors found priming within Dutch (Experiment 1) and within English as a 2nd language (Experiments 2 and 4). An important finding is that priming occurred from Dutch to German (Experiment 5), which both have verb-final relative clauses; but it did not occur between Dutch and English (Experiments 3 and 4), which differ in relative-clause word order. The results suggest that word-order repetition is needed for the construction of integrated syntactic representations. PMID- 17723071 TI - No retrieval-induced forgetting using item-specific independent cues: evidence against a general inhibitory account. AB - Retrieval practice with particular items from memory can impair the recall of related items on a later memory test. This retrieval-induced forgetting effect has been ascribed to inhibitory processes (M. C. Anderson & B. A. Spellman, 1995). A critical finding that distinguishes inhibitory from interference explanations is that forgetting is found with independent (or extralist) cues. In 4 experiments, the authors tested whether the forgetting effect is cue independent. Forgetting was investigated for both studied and unstudied semantically related items. Retrieval-induced forgetting was not found using item specific independent cues for either studied or unstudied items. However, forgetting was found for both item types when studied categories were used as cues. These results are not in line with a general inhibitory account, because this account predicts retrieval-induced forgetting with independent cues. Interference and context-specific inhibition are discussed as possible explanations for the data. PMID- 17723072 TI - Binding facilitates attention switching within working memory. AB - The authors investigated the units of selective attention within working memory. In Experiment 1, a group of participants kept 1 count and 1 location in working memory and updated them repeatedly in random order. Another group of participants were instructed to achieve the same goal by memorizing the verbal and spatial information in an integrative way as a moving digit. The behavioral data showed that switching attention between properties of an integrated working-memory item was faster than switching between respective properties of different items. Experiment 2 demonstrated that this switching facilitation cannot be simply ascribed to the different amount of working-memory items maintained by the two groups of participants. Finally, by adopting a pure verbal task in Experiment 3, the authors observed the same binding facilitation, with the possibility of "location-based selection" excluded. They summarize the observations of all 3 experiments in the study and suggest both a location- and object-based mechanism for attention selection in working memory. PMID- 17723073 TI - Teaching adults new words: the role of practice and consolidation. AB - Semantic and orthographic learning of new words was investigated with the help of the picture-word interference (PWI) task. In this version of the Stroop task, picture naming is delayed by the simultaneous presentation of a semantically related as opposed to an unrelated distractor word (a specific PWI effect), as well as by an unrelated word compared with a nonword (a general PWI effect). This interference is taken to reflect automatic orthographic and semantic processing. The authors observed that participants showed both types of PWI effects for newly learned words following a single study session. Interestingly, specific PWI effects were not obtained immediately after testing but did emerge a week later without additional practice. This suggests that a period of consolidation is involved in the establishment of word representations. In addition, identical PWI effects were obtained when the study and test words were presented in either the same or different letter case. This provides evidence that the newly acquired orthographic representations are coded in an abstract format. PMID- 17723074 TI - The crucial role of postcue encoding in directed forgetting and context-dependent forgetting. AB - People can intentionally forget previously studied material if, after study, a forget cue is provided and new material is learned. It has recently been suggested that such list-method directed forgetting arises because the forget cue induces a change in internal context and causes context-dependent forgetting of the studied material (L. Sahakyan & C. M. Kelley, 2002). The authors compared directed forgetting and context-dependent forgetting by examining whether, like a forget cue, a change in internal context needs subsequent learning of new material to be effective. Participants studied an item list and, after study, received a remember cue or a forget cue or their internal context was changed through an imagination task. In each condition, half the participants learned a second list, and the other half fulfilled an unrelated distractor task. Both the forget cue and the change in internal context induced forgetting of the first list only when learning of the second list was interpolated. These results suggest that postcue encoding of new material is crucial for both directed forgetting and (some forms of) context-dependent forgetting. PMID- 17723075 TI - Does therapeutic use of acetaminophen cause acute liver failure? AB - STUDY OBJECTIVE: To compare the reported occurrence of liver failure in subjects in prospective trials with that in patients in retrospective reports after repeated use of therapeutic dosages of acetaminophen. DESIGN: Systematic review of the medical literature. DATA SOURCE: MEDLINE and EMBASE biomedical and pharmacologic databases. SUBJECTS: Adults who received repeated dosing of acetaminophen 4 g/day or lower for at least 24 hours. MEASUREMENTS AND MAIN RESULTS: Articles written in several languages were abstracted by trained personnel using a structured abstraction form. Data were categorized by methodology (prospective vs retrospective), acetaminophen dosage, and type of liver effect. A total of 791 articles were identified, which included 30,865 subjects in prospective studies and 9337 patients in retrospective reports. The prospective studies reported no cases of fulminant hepatic injury, liver transplantation, or death due to acetaminophen. Of the 30,865 subjects in these studies, 129 (0.4%) were identified who had a serum aminotransferase level that exceeded the upper limit of normal, including 61 subjects in randomized trials in which the proportion of serum aminotransferase level increase was the same as or less than that in the placebo group and 68 subjects in trials without a placebo group. In addition, 4263 (13.8%) received the maximum recommended therapeutic dosage (3.9-4 g/day). In the retrospective reports, 96 patients (1.0%) had a serum alanine aminotransferase level that exceeded the upper limit of normal, one (0.01%) underwent liver transplantation, and six (0.06%) died. Causality relationship of acetaminophen for each retrospective case was assessed with the Naranjo adverse drug reaction probability scale. The mean +/- SD Naranjo score for all 103 retrospective cases was 3.2 +/- 1.9, indicating a possible relationship between the increased aminotransferase levels and acetaminophen use. Some retrospective reports contained information suggesting that the patient had ingested an overdose despite a history of therapeutic use. CONCLUSION: Prospective studies indicated that repeated use of a true therapeutic acetaminophen dosage may slightly increase the level of serum aminotransferase activity, but hepatic failure or death was not reported. Retrospective reports indicated a higher rate of increased serum aminotransferase levels, and several reported associated liver injury and death. The differing results and presence of evidence indicating inaccurate acetaminophen dosage information in some case reports suggests that these cases may be inadvertent overdoses, rather than true therapeutic dosages. PMID- 17723076 TI - Comparison of the dose response to levalbuterol with and without pretreatment with S-albuterol after methacholine-induced bronchoconstriction. AB - STUDY OBJECTIVE: To determine the effect of S-albuterol on the dose response to levalbuterol in patients with moderate bronchoconstriction induced by a methacholine challenge. DESIGN: Prospective, randomized, double-blind, placebo controlled, crossover study. SETTING: University-affiliated clinical trial center. PATIENTS: Twenty-two adults with mild, stable asthma. INTERVENTION: At the screening visit, patients were switched from their beta2-agonist to ipratropium bromide for use as an as-needed rescue therapy. At the baseline visit 2-6 days later, the provocative concentration of methacholine to induce a 30% decrease in forced expiratory volume in 1 second (FEV(1) PC(30)) was determined, followed by a nebulized racemic albuterol dose-response study with three doses of albuterol, to familiarize patients with the procedures. At visits 2 and 3, patients were randomly assigned to receive nebulized normal saline placebo or S albuterol 5 mg before the methacholine challenge and were administered three escalating doses of levalbuterol after the challenge. MEASUREMENTS AND MAIN RESULTS: Area under the curve for FEV(1) over 40 minutes (AUC(0-40)) after administration of levalbuterol was the primary outcome, with slope of FEV(1) as the secondary outcome. In addition, the fraction of exhaled nitric oxide (FeNO) was measured before and after the challenges. In the 17 patients who met criteria for completion, no deleterious effect for S-albuterol was found for FEV(1) PC(30), AUC(0-40) FEV(1), or the FEV(1) slope(0-40). However, S-albuterol reduced the provocative concentration of methacholine to induce a 20% decrease in FEV(1) (PC(20) 0.52 +/- 2.06 vs 0.39 +/- 1.58 mg/ml, placebo vs S-albuterol, p=0.044) but did not affect FeNO. CONCLUSION: A single high dose of S-albuterol did not alter the bronchodilator response to levalbuterol. The effect on bronchial responsiveness requires further study. PMID- 17723077 TI - Risk of warfarin-related bleeding events and supratherapeutic international normalized ratios associated with complementary and alternative medicine: a longitudinal analysis. AB - STUDY OBJECTIVE: To determine the risk of bleeding and supratherapeutic international normalized ratios (INRs) associated with use of complementary and alternative medicine (CAM) in patients receiving warfarin. DESIGN: Prospective, longitudinal study. SETTING: An acute care, academic and research hospital in Canada. PATIENTS: A total of 171 adults who were prescribed warfarin anticoagulation therapy for an expected duration of at least 4 months after enrollment. INTERVENTION: Patients were asked to complete a 16-week diary by recording bleeding events and exposure to factors previously reported to increase the risk of bleeding and supratherapeutic INRs, including CAM consumption. MEASUREMENTS AND MAIN RESULTS: Prescription, medical, and laboratory records were reviewed. Risk factors for bleeding events and supratherapeutic INR (at least 0.5 units above the target range) were evaluated longitudinally by using generalized estimating equation (GEE) modeling. Of the 171 patients completing a diary, 87 (51%) reported at least one bleeding event and 36 (21%) had a supratherapeutic INR. Seventy-three patients (43%) indicated they had used at least one CAM product previously reported to interact with warfarin. Warfarin use of less than 3 months' duration was the only statistically significant risk factor identified for supratherapeutic INR. The CAM therapies associated with an increased risk of self-reported bleeding included cayenne, ginger, willow bark, St. John's wort, and coenzyme Q(10). Use of more than one CAM while receiving warfarin was also a significant risk factor. Two CAMs were independently associated with an increased risk of self-reported bleeding: coenzyme Q(10) (odds ratio [OR] 3.69, 95% confidence interval [CI] 1.88-7.24) and ginger (OR 3.20, 95% CI 2.42-4.24). Other risk factors significantly associated with increased bleeding included high target INR (2.5-3.5), diarrhea, acetaminophen use, increased alcohol consumption, and increased age. CONCLUSIONS: The use of CAM by patients receiving warfarin is common, and consumption of coenzyme Q(10) or ginger appears to increase the risk of bleeding in this population. PMID- 17723078 TI - T-cell responses to hepatitis B surface antigen in lung transplant recipients. AB - STUDY OBJECTIVE: To determine whether lung transplant recipients would have a less vigorous T-cell response to hepatitis B surface antigen (HBsAg) than that of patients awaiting lung transplantation and healthy subjects, we sought to measure and compare T-cell responses among these three groups. DESIGN: Prospective study. SETTING: Lung transplant clinic at a university hospital. SUBJECTS: Twelve lung transplant recipients, 12 patients awaiting lung transplantation, and 15 healthy subjects. All participants had received the hepatitis B vaccine series and had a documented antibody response to it. INTERVENTION: Blood samples were obtained from each participant. MEASUREMENTS AND MAIN RESULTS: Participants' sex, age, time since lung transplantation (if applicable), and time since hepatitis B immunization were recorded. Peripheral blood mononuclear cells were isolated from the participants' blood samples for the trans vivo delayed-type hypersensitivity (DTH) assay. These cells were mixed with saline, tetanus toxoid, or HBsAg and injected into the footpads of immunodeficient mice. Resultant swelling of the footpad was used as an index of human T-cell response. The healthy subjects were younger than the patients in both transplant groups. However, we found no significant difference in DTH response elicited by HBsAg among the healthy subjects, patients awaiting lung transplantation, and lung transplant recipients (mean +/- standard error [SE] 34.7 +/- 4.3, 32.1 +/- 3.1, and 33.5 +/- 4.0 x 10( 4) in., respectively, p>0.8) or when tetanus toxoid was used as a positive control (15.7 +/- 2.8, 22.8 +/- 6.5, and 21.7 +/- 3.9 x 10(-4) in., respectively, p>0.3). No correlation between age or time since immunization and DTH response was noted. CONCLUSION: Lung transplant recipients maintained a T-cell response to HBsAg that was similar in vigor to that of both patients awaiting transplantation and healthy subjects even though their antibody concentrations waned rapidly after transplantation. The role of these T cells as a correlate of protection from infection remains to be investigated. PMID- 17723079 TI - Pharmacokinetics of a guanfacine extended-release formulation in children and adolescents with attention-deficit-hyperactivity disorder. AB - STUDY OBJECTIVE: To evaluate the single- and multiple-dose pharmacokinetics of an oral extended-release formulation of guanfacine in children and adolescents with a diagnosis of attention-deficit-hyperactivity disorder (ADHD). DESIGN: Phase I II, open-label, dose-escalation study. SETTING: Clinical study center. PATIENTS: Fourteen children (aged 6-12 yrs) and 14 adolescents (aged 13-17 yrs) with ADHD. INTERVENTION: All patients received guanfacine as a single 2-mg dose on day 1. They received a daily dose of 2 mg on days 9-15, 3 mg on days 16-22, and 4 mg on days 23-29. MEASUREMENTS AND MAIN RESULTS: Blood samples, vital signs, and electrocardiograms (ECGs) were obtained before dosing on day 1 and at intervals over 24 hours, with repeat measurements on days 14 and 28. Guanfacine demonstrated linear pharmacokinetics. Mean plasma concentrations, peak exposure (C(max)), and total or 24-hour exposure (area under the concentration-time curve [AUC](0-infinity) or AUC(0-24), respectively) were as follows in children and adolescents, respectively: after a single 2-mg dose, AUC(0-infinity) was 65.2 +/- 23.9 ng x hour/ml and 47.3 +/- 13.7 ng x hour/ml and C(max) was 2.55 +/- 1.03 ng x ml and 1.69 +/- 0.43 ng/ml after multiple 2-mg doses, AUC(0-24) was 70.0 +/- 28.3 ng x hour/ml and 48.2 +/- 16.1 ng x hour/ml and C(max) was 4.39 +/- 1.66 ng/ml and 2.86 +/- 0.77 ng/ml; and after multiple 4-mg doses, AUC(0-24) was 162 +/- 116 ng x hour/ml and 117 +/- 28.4 ng x hour/ml and C(max) was 10.1 +/- 7.09 ng/ml and 7.01 +/- 1.53 ng/ml. After a single 2-mg dose, half-life was 14.4 +/- 2.39 hours in children and 17.9 +/- 5.77 hours in adolescents. The most frequent treatment-emergent adverse events were somnolence, insomnia, headache, blurred vision, and altered mood. Most were mild to moderate in severity, with the highest frequency associated with the 4-mg doses. Blood pressure, pulse, and ECG reading.hour/ml s were all within normal limits. CONCLUSION: Guanfacine extended release formulation demonstrated linear pharmacokinetics. Plasma concentrations and concentration-related pharmacokinetic parameters were higher in children than in adolescents. These differences are likely due to heavier body weights in adolescents and young male subjects. No serious adverse events were reported. PMID- 17723080 TI - Enoxaparin use in the neonatal intensive care unit: experience over 8 years. AB - STUDY OBJECTIVE: To evaluate the effectiveness and safety of enoxaparin therapy in a neonatal intensive care unit (NICU). DESIGN: Retrospective chart review. SETTING: Level III NICU in a Canadian academic center. PATIENTS: All neonates treated with enoxaparin while in the NICU between January 1, 1998, and June 1, 2006. MEASUREMENTS AND MAIN RESULTS: Data abstracted included patient demographics, diagnosis of thrombosis and its progression, enoxaparin dosages with corresponding antifactor Xa levels, and adverse events. Sixteen neonates (four term, 12 preterm) were treated with enoxaparin at a mean +/- SD initial subcutaneous dose of 1.41 +/- 0.15 mg/kg every 12 hours. The target therapeutic range (antifactor Xa level 0.5-1.0 U/ml) was achieved by 12 infants at a mean +/- SD dose of 1.92 +/- 0.43 mg/kg every 12 hours, after a mean of 5.6 days (range 1 15 days). Preterm infants required a higher dose (per kilogram) compared with term infants to maintain therapeutic antifactor Xa levels (mean +/- SD 1.94 +/- 0.39 vs 1.65 +/- 0.14 mg/kg every 12 hrs, p<0.001). Enoxaparin doses were more strongly correlated to antifactor Xa levels in term infants (r(2)=0.51, p<0.001) compared with preterm infants (r(2)=0.20, p<0.001). Ten (71%) of 14 thromboembolic events resolved, either partially or completely, at a mean of 39 days (range 8-61 days) of enoxaparin therapy. Nine infants (56%) experienced minor local adverse effects at the site of the indwelling subcutaneous catheter (induration, bruises, hematomas, or leakage). Systemic adverse events that were possibly related to enoxaparin therapy included osteopenia (one infant), scleral hemorrhage (one), and minor gastrointestinal tract bleeding (three) found in gastric feeding tubes. No adverse effects were associated with antifactor Xa levels greater than 1.0 U/ml. CONCLUSION: Enoxaparin may be effective in the treatment of neonatal thrombosis. An initial dosage of 1.5 mg/kg every 12 hours is likely inadequate to obtain therapeutic antifactor Xa levels rapidly and differs for term and preterm neonates. Therapeutic levels in preterm infants may be more variable, and the pharmacokinetics of this drug in preterm infants requires further evaluation. Future studies in neonates should prospectively evaluate a higher starting dose of enoxaparin to document effectiveness, acceptance, compliance with treatment guidelines, and adverse effects. PMID- 17723082 TI - Potential roles for statins in critically ill patients. AB - The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the most commonly prescribed agents for hypercholesterolemia and have revolutionized the management of hyperlipidemia and the area of cardiovascular risk reduction. However, recent data suggest that their effects go well beyond the lipid lowering seen with long-term use and may include acute antiinflammatory activity, anticoagulation, immunomodulation, as well as promotion of changes in smooth muscle tone. Because of these data, promising research has begun into the use of these agents in various critical care areas such as the early phases of sepsis, bacteremia, and ischemic stroke. Recent data also show a decrease in cerebral vasospasm after subarachnoid hemorrhage, an area deficient in therapeutic options. More research is necessary to ascertain the true role of statins in the treatment of these various disorders. Nevertheless, the concept of a statin's role as being only a routine preventive therapy with benefits limited to patients undergoing extended treatment is rapidly becoming inaccurate. PMID- 17723081 TI - Lack of an effect of oral iron administration on mycophenolic acid pharmacokinetics in stable renal transplant recipients. AB - STUDY OBJECTIVES: To determine if coadministration of polysaccharide iron complex and slow-release ferrous sulfate alter the absorption of mycophenolic acid (MPA), and to examine the potential influence of dosing relative to mycophenolate mofetil (MMF) administration and the effect of immediate- versus sustained release iron products on the steady-state pharmacokinetics of MPA. DESIGN: Prospective, open-label, three-phase, crossover, steady-state pharmacokinetic study. SETTING: National Institutes of Health-sponsored General Clinical Research Center at a university medical center. PATIENTS: Twelve adult (mean age 50 yrs) renal transplant recipients who were receiving concomitant iron and MMF maintenance therapy. INTERVENTION: Oral iron therapy was coadministered with MMF on days -6-0, MMF was administered alone on days 1-8 (control phase), then oral iron therapy was administered 2 hours after MMF administration on days 9-16. MEASUREMENTS AND MAIN RESULTS: Baseline demographics, concurrent drug regimens, and clinical laboratory values were assessed. Blood samples were obtained at baseline and at 1, 2, 3, 4, 6, 8, and 12 hours after MMF administration on days 0, 8, and 16. The MPA levels were measured by high-performance liquid chromatography. We found no significant differences in the dose-standardized area under the concentration-time curve from 0-12 hours (AUC(0-12)) for MPA between the control phase (39.66 +/- 8.70 mg mg x hr/L) and the concomitant ferrous sulfate or dose-separated ferrous sulfate (37.56 +/- 9.95 or 32.84 +/- 8.43 mg x hr/L, respectively, p>0.05) phases. Dose-standardized AUC(0-12) values for MPA did not significantly differ after the concomitant administration of polysaccharide iron complex from that of the control phase (48.46 +/- 9.68 and 43.80 +/- 9.46 mg x hr/L, respectively, p=0.065). However, the AUC(0-12) for MPA significantly increased when polysaccharide iron complex was administered 2 hours after MMF (53.41 +/- 11.75 mg x hr/L, p=0.012). Maximum concentrations and times to reach maximum concentrations remained consistent across all study phases in each arm of the trial (p>0.05). CONCLUSION: Multiple doses of iron therapy-slow release ferrous sulfate, or polysaccharide iron complex-did not significantly reduce systemic exposure to MMF, as measured by using AUC(0-12) values. PMID- 17723083 TI - Monotherapy versus combination therapy with class III antiarrhythmic agents to attenuate transmural dispersion of repolarization: a potential risk factor for torsade de pointes. AB - Class III antiarrhythmic agents are used for conversion to and maintenance of sinus rhythm from arrhythmias of atrial or ventricular origin. Monotherapy can be limited by adverse events or recurrent arrhythmias. Sotalol, dofetilide, and ibutilide may induce torsade de pointes in 2-8% of patients, whereas amiodarone induces torsade de pointes in less than 1%. We reviewed the literature regarding the possible combination of class III antiarrhythmics and risk for inducing torsade de pointes. Animal studies using amiodarone plus sotalol or d-sotalol suggest that these drug combinations prolong the QTc interval but do not induce torsade de pointes. Similar data extracted from human studies of ibutilide in patients also receiving amiodarone or sotalol showed greater efficacy with combination therapy than with monotherapy, without increased torsade de pointes induction. Reduced transmural dispersion of repolarization with amiodarone and sotalol combination therapy may serve as a mechanism for reducing the risk of torsade de pointes compared with sotalol monotherapy. PMID- 17723084 TI - The utility of hospital antibiograms as tools for guiding empiric therapy and tracking resistance. Insights from the Society of Infectious Diseases Pharmacists. AB - Hospital antibiograms are commonly used to help guide empiric antimicrobial treatment and are an important component of detecting and monitoring trends in antimicrobial resistance. To serve these purposes, antibiograms must be constructed using standardized methods that allow inter- and intrahospital comparisons. Antibiograms that include surveillance cultures and duplicate bacterial isolates can overestimate rates of resistance. In 2002, the National Committee for Clinical Laboratory Standards (now known as the Clinical and Laboratory Standards Institute [CLSI]) published standards for constructing antibiograms. According to national surveys, many of the recommended elements of the CLSI document have not been fully adopted. In lieu of full compliance with CLSI standards, it is necessary that the methods used to construct antibiograms are clearly delineated. Antibiograms have several limitations, such as their inability to track emergence of resistance during therapy. The antibiogram can serve as a valuable tool in guiding antimicrobial therapy, but other patient factors, such as previous infection history and antibiotic use, also need to be considered. Additional data are needed for specialized applications of resistance analyses. PMID- 17723085 TI - Interference of maltose, icodextrin, galactose, or xylose with some blood glucose monitoring systems. AB - Maltose, a disaccharide composed of two glucose molecules, is used in a number of biological preparations as a stabilizing agent or osmolality regulator. Icodextrin, which is converted to maltose, is present in a peritoneal dialysis solution. Galactose and xylose are found in some foods, herbs, and dietary supplements; they are also used in diagnostic tests. When some blood glucose monitoring systems are used--specifically, those that use test strips containing the enzymes glucose dehydrogenase-pyrroloquinolinequinone or glucose dye oxidoreductase--in patients receiving maltose, icodextrin, galactose, or xylose, interference of blood glucose levels can occur. Maltose, icodextrin, galactose, and xylose are misinterpreted as glucose, which can result in erroneously elevated serum glucose levels. This interference can result in the administration of insulin, which may lead to hypoglycemia. In severe cases of hypoglycemia, deaths have occurred. If patients are receiving maltose, icodextrin, galactose, or xylose, clinicians must review the package inserts of all test strips to determine the type of glucose monitoring system being used and to use only those systems whose tests strips contain glucose oxidase, glucose dehydrogenase nicotinamide adenine dinucleotide, or glucose dehydrogenase-flavin adenine dinucleotide. PMID- 17723086 TI - Discordant effects of beta-blockade on central aortic systolic and brachial systolic blood pressure: considerations beyond the cuff. AB - The role of beta-blockers in uncomplicated hypertension has been challenged recently. Compared with other antihypertensives, beta-blockers are less effective for preventing cardiovascular events in patients with uncomplicated hypertension. Moreover, a recent meta-analysis of placebo-controlled clinical trials concluded that atenolol is not more efficacious than placebo for preventing cardiovascular events in patients with hypertension. Although these agents lower blood pressure measured conventionally over the brachial artery with a blood pressure cuff, they do not exert a commensurate effect on blood pressure in the central aorta. Central aortic blood pressure and aortic augmentation index are strong predictors of left ventricular hypertrophy, an independent risk factor for cardiovascular events. Emerging data are illuminating the antihypertensive paradox whereby antihypertensive agents may elicit discordant effects on central and peripheral blood pressure and hemodynamics. Vasodilatory antihypertensives, such as renin angiotensin-aldosterone system inhibitors and calcium channel blockers, elicit reductions in central aortic blood pressure equal to or greater than that in the brachial artery. Conversely, beta-blockers lower central aortic blood pressure to a lesser degree even when blood pressure measured by sphygmomanometry is reduced substantially. Given the strong relationship between central aortic blood pressure and target organ damage, the effectiveness of beta-blockers may be overestimated in practice on the basis of conventional blood pressure measurements alone. Differences in central and peripheral blood pressure may account for the lack of cardiovascular protection afforded by beta-blockers in clinical trials and could account for a portion of the apparent "benefit beyond blood pressure" reduction with other classes of antihypertensive agents. Future studies should aim to better clarify the role of central aortic blood pressure in the treatment of hypertension. In the meantime, the effects of antihypertensive drugs on blood pressure "beyond the brachial blood pressure cuff" should be considered when prescribing antihypertensive agents for a patient. PMID- 17723087 TI - Safe use of meropenem in a patient with a possible nonimmediate allergy to imipenem. AB - Strong data are lacking on the cross-reactivity between individual carbapenems. We describe a 48-year-old woman with ventilator-associated Pseudomonas aeruginosa pneumonia who received an 8-day course of imipenem-cilastatin and experienced a delayed (i.e., nonimmediate) hypersensitivity reaction, evidenced by an extensive erythematous macular morbilliform rash and an increased eosinophil count. Eight days after completion of therapy, the pneumonia returned, and it was decided to avoid using imipenem-cilastatin; she was administered a 14-day course of meropenem. To our knowledge, this is the first report of a nonimmediate hypersensitivity reaction to imipenem-cilastatin without cross-reactivity to meropenem. This suggests that if carbapenem therapy is unavoidable, meropenem may be cautiously administered in patients with a known allergy to imipenem cilastatin. PMID- 17723088 TI - Agitation associated with aripiprazole initiation. AB - Aripiprazole is a novel antipsychotic with a mechanism of action different from those of traditional first- and second-generation antipsychotics. We describe three patients with long histories of treatment for schizophrenia or schizoaffective disorder in whom conversion to aripiprazole was being attempted. After they started aripiprazole, their psychosis, agitation, anxiety, or aggression worsened. Although the cause of the increased agitation was unclear, it may have been related to long-term use of dopamine-blocking antipsychotics and resultant upregulation of postsynaptic dopamine receptors. The mechanism of partial dopamine agonism observed with aripiprazole may increase dopaminergic activity and worsen positive dopamine-associated symptoms, such as paranoia, agitation, and aggression. The treatment of schizophrenia is often a clinical challenge, particularly when patients have a long history of noncompliance and poor response. Clinicians face difficult decisions in finding an effective and well-tolerated regimen. These cases magnify some of the challenges and provide insight into the clinical implications of converting to therapies with different pharmacodynamic effects. PMID- 17723089 TI - Clindamycin-induced Sweet's syndrome. AB - Drug-induced acute febrile neutrophilic dermatosis, or Sweet's syndrome, is rare and, to our knowledge, has not previously been associated with clindamycin therapy. We describe a 47-year-old woman with type 2 diabetes mellitus and end stage renal disease requiring hemodialysis who developed Sweet's syndrome after receiving oral and intravenous clindamycin for a tooth infection. After the clindamycin was discontinued, the patient's clinical symptoms resolved over several days. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship between the patient's development of Sweet's syndrome and clindamycin therapy. Clinicians should be aware that Sweet's syndrome can occur with clindamycin treatment. Early recognition of this condition in conjunction with cessation of drug exposure, with or without antiinflammatory therapy, can produce complete recovery. PMID- 17723090 TI - A concept for NASA's Mars 2016 astrobiology field laboratory. AB - The Mars Program Plan includes an integrated and coordinated set of future candidate missions and investigations that meet fundamental science objectives of NASA and the Mars Exploration Program (MEP). At the time this paper was written, these possible future missions are planned in a manner consistent with a projected budget profile for the Mars Program in the next decade (2007-2016). As with all future missions, the funding profile depends on a number of factors that include the exact cost of each mission as well as potential changes to the overall NASA budget. In the current version of the Mars Program Plan, the Astrobiology Field Laboratory (AFL) exists as a candidate project to determine whether there were (or are) habitable zones and life, and how the development of these zones may be related to the overall evolution of the planet. The AFL concept is a surface exploration mission equipped with a major in situ laboratory capable of making significant advancements toward the Mars Program's life-related scientific goals and the overarching Vision for Space Exploration. We have developed several concepts for the AFL that fit within known budget and engineering constraints projected for the 2016 and 2018 Mars mission launch opportunities. The AFL mission architecture proposed here assumes maximum heritage from the 2009 Mars Science Laboratory (MSL). Candidate payload elements for this concept were identified from a set of recommendations put forth by the Astrobiology Field Laboratory Science Steering Group (AFL SSG) in 2004, for the express purpose of identifying overall rover mass and power requirements for such a mission. The conceptual payload includes a Precision Sample Handling and Processing System that would replace and augment the functionality and capabilities provided by the Sample Acquisition Sample Processing and Handling system that is currently part of the 2009 MSL platform. PMID- 17723091 TI - Searching for life on Mars: selection of molecular targets for ESA's aurora ExoMars mission. AB - The European Space Agency's ExoMars mission will seek evidence of organic compounds of biological and non-biological origin at the martian surface. One of the instruments in the Pasteur payload may be a Life Marker Chip that utilizes an immunoassay approach to detect specific organic molecules or classes of molecules. Therefore, it is necessary to define and prioritize specific molecular targets for antibody development. Target compounds have been selected to represent meteoritic input, fossil organic matter, extant (living, recently dead) organic matter, and contamination. Once organic molecules are detected on Mars, further information is likely to derive from the detailed distribution of compounds rather than from single molecular identification. This will include concentration gradients beneath the surface and gradients from generic to specific compounds. The choice of biomarkers is informed by terrestrial biology but is wide ranging, and nonterrestrial biology may be evident from unexpected molecular distributions. One of the most important requirements is to sample where irradiation and oxidation are minimized, either by drilling or by using naturally excavated exposures. Analyzing regolith samples will allow for the search of both extant and fossil biomarkers, but sequential extraction would be required to optimize the analysis of each of these in turn. PMID- 17723092 TI - Porphyrin as an ideal biomarker in the search for extraterrestrial life. AB - A key issue in astrobiological research is identifying target molecules that are unambiguously biological in origin and can be easily detected and recognized. We suggest porphyrin derivatives as an ideal target, because these chromophores are global in distribution and found in virtually all living organisms on Earth, including microorganisms that may approximate the early evolution of life on Earth. We discuss the inherent qualities that make porphyrin ideally suited for astrobiological research and discuss methods for detecting porphyrin molecules in terrestrial sedimentary environments. We present preliminary data to support the use of ToFSIMS as a powerful technique in the identification of porphyrins. PMID- 17723093 TI - Origin of informational polymers and the search for non-terran life: protection of the polymeric state of DNA by phosphate minerals. AB - An in-depth analysis of the effects exerted on the DNA backbone by 25 crystal phosphate minerals is reported. Degradation of DNA oligomers was performed with two different reactions: Hydrolysis following Nucleophilic Degradation (HND), initiated by the nucleophilic addition of formamide on both purine and pyrimidine nucleobases, and Hydrolysis following Nucleophilic Substitution (HNS) carried on by water and starting with the removal of a nondegraded base. A complete panel of effects on the phosphoester bonds, from protection to enhanced instability to absence of interference, is described. These effects differ in the different degradation pathways and in different physical-chemical conditions. The relationship between the hardness of the mineral and its protective ability is discussed. In addition to its interest per se, this study was prompted by the observed catalytic abilities of soluble and mineral phosphates (Saladino et al., 2006c) on the synthetic reactions by formamide. The relevance of these observations in the search for nonterran life is discussed. PMID- 17723094 TI - Carotenoid analysis of halophilic archaea by resonance Raman spectroscopy. AB - Recently, halite and sulfate evaporate rocks have been discovered on Mars by the NASA rovers, Spirit and Opportunity. It is reasonable to propose that halophilic microorganisms could have potentially flourished in these settings. If so, biomolecules found in microorganisms adapted to high salinity and basic pH environments on Earth may be reliable biomarkers for detecting life on Mars. Therefore, we investigated the potential of Resonance Raman (RR) spectroscopy to detect biomarkers derived from microorganisms adapted to hypersaline environments. RR spectra were acquired using 488.0 and 514.5 nm excitation from a variety of halophilic archaea, including Halobacterium salinarum NRC-1, Halococcus morrhuae, and Natrinema pallidum. It was clearly demonstrated that RR spectra enhance the chromophore carotenoid molecules in the cell membrane with respect to the various protein and lipid cellular components. RR spectra acquired from all halophilic archaea investigated contained major features at approximately 1000, 1152, and 1505 cm(-1). The bands at 1505 cm(-1) and 1152 cm( 1) are due to in-phase C=C (nu(1) ) and C-C stretching ( nu(2) ) vibrations of the polyene chain in carotenoids. Additionally, in-plane rocking modes of CH(3) groups attached to the polyene chain coupled with C-C bonds occur in the 1000 cm( 1) region. We also investigated the RR spectral differences between bacterioruberin and bacteriorhodopsin as another potential biomarker for hypersaline environments. By comparison, the RR spectrum acquired from bacteriorhodopsin is much more complex and contains modes that can be divided into four groups: the C=C stretches (1600-1500 cm(-1)), the CCH in-plane rocks (1400-1250 cm(-1)), the C-C stretches (1250-1100 cm(-1)), and the hydrogen out-of plane wags (1000-700 cm(-1)). RR spectroscopy was shown to be a useful tool for the analysis and remote in situ detection of carotenoids from halophilic archaea without the need for large sample sizes and complicated extractions, which are required by analytical techniques such as high performance liquid chromatography and mass spectrometry. PMID- 17723096 TI - Biomarker and stable isotope characterization of coastal pond-derived organic matter, McMurdo Dry Valleys, Antarctica. AB - Small coastal ponds that contain photosynthetic microbial mat communities represent an extreme environment where a potentially significant source of labile organic carbon can be found within the McMurdo Dry Valleys, Antarctica. To distinguish coastal pond-derived organic matter from other sources of organic matter in the Dry Valleys, bulk organic carbon, nitrogen, and sulfur isotope signatures and phospholipid fatty acid (PLFA) profiles of benthic microbial mats located at two sites--Hjorth Hill coast and Garwood Valley--were investigated. The average isotope values at Hjorth Hill coast and Garwood Valley are, respectively, -10.9 per thousand and -10.2 per thousand for delta(13) C, 3.7 per thousand and -1.3 per thousand for delta(15)N, and 8.1 per thousand and 16.7 per thousand for delta(34)S. Microbial mats from all ponds are dominated by monounsaturated PLFAs (indicative of Gram-negative bacteria) and polyunsaturated PLFAs (indicative of microeukaryotes). Biomarkers specific to aerobic prokaryotes, eukaryotes, and photoautotrophic microeukaryotes, as well as sulfur reducing bacteria, are present in all samples. Benthic mats at Garwood Valley are thicker and more laminated, have a higher biomass, and have a greater carbon and nitrogen content, which suggests greater productivity than mats at Hjorth Hill coast. Greater productivity is supported, as well, by higher dissolved oxygen contents likely derived from heightened photosynthetic productivity. More productivity at Garwood Valley likely results from a larger influx of terrestrial surface waters together with a concomitant nutrient loading. PMID- 17723097 TI - Biogeochemistry of hypersaline springs supporting a mid-continent marine ecosystem: an analogue for martian springs? AB - Hypersaline springs that host unique mid-continent marine ecosystems were examined in central Manitoba, Canada. The springs originate from a reflux of glacial meltwater that intrudes into underlying bedrock and dissolved buried salt beds. Two spring types were distinguished based both on flow rate and geochemistry. High flow springs (greater than 10 L/s) hosted extensive marine microbial mats, which were dominated by algae but also included diverse microbes. These varied somewhat between springs as indicated by changes in profiles of fatty acid methyl esters. Culture studies confirmed the presence of sulfate reducing bacteria in sediments at the high flow sites. In contrast, low flow springs were affected by solar evaporation, increasing salinity, and temperature. These low flow springs behaved more like closed nutrient-limited systems and did not support microbial mats. Direct comparison of the high and low flow springs revealed interesting implications for the potential to record biosignatures in the rock record. High flow springs have abundant, well-developed microbial mats, which desiccate and are cemented along the edges of the spring pools; however, the high mass flux overwhelms any geochemical signature of microbial activity. In contrast, the nutrient-limited low flow sites develop strong geochemical signatures of sulfate reduction, even in the absence of microbial mats, due to less dilution with the lower flows. Geochemical and physical evidence for life did not correlate with the abundance of microbial life but, rather, with the extent to which the biological system formed a closed ecosystem. PMID- 17723098 TI - Ultrastructural and geochemical characterization of Archean-Paleoproterozoic graphite particles: implications for recognizing traces of life in highly metamorphosed rocks. AB - Abundant graphite particles occur in amphibolite-grade quartzite of the Archean Paleoproterozoic Wutai Metamorphic Complex in the Wutaishan area of North China. Petrographic thin section observations suggest that the graphite particles occur within and between quartzite clasts and are heterogeneous in origin. Using HF maceration techniques, the Wutai graphite particles were extracted for further investigation. Laser Raman spectroscopic analysis of a population of extracted graphite discs indicated that they experienced a maximum metamorphic temperature of 513 +/- 50 degrees C, which is consistent with the metamorphic grade of the host rock and supports their indigenicity. Scanning and transmission electron microscopy revealed that the particles bear morphological features (such as hexagonal sheets of graphite crystals) related to metamorphism and crystal growth, but a small fraction of them (graphite discs) are characterized by a circular morphology, distinct marginal concentric folds, surficial wrinkles, and complex nanostructures. Ion microprobe analysis of individual graphite discs showed that their carbon isotope compositions range from -7.4 per thousand to 35.9 per thousand V-PDB (Vienna Pee Dee Belemnite), with an average of -20.3 per thousand, which is comparable to bulk analysis of extracted carbonaceous material. The range of their size, ultrastructures, and isotopic signatures suggests that the morphology and geochemistry of the Wutai graphite discs were overprinted by metamorphism and their ultimate carbon source probably had diverse origins that included abiotic processes. We considered both biotic and abiotic origins of the carbon source and graphite disc morphologies and cannot falsify the possibility that some circular graphite discs characterized by marginal folds and surficial wrinkles represent deflated, compressed, and subsequently graphitized organic-walled vesicles. Together with reports by other authors of acanthomorphic acritarchs from greenschist-amphibolite-grade metamorphic rocks, this study suggests that it is worthwhile to examine carbonaceous materials preserved in highly metamorphosed rocks for possible evidence of ancient life. PMID- 17723101 TI - Sharing the mystery: science as exploration. PMID- 17723102 TI - The science of storytelling. PMID- 17723103 TI - The power of our myth. PMID- 17723104 TI - Changes in the transcriptional profile of cardiac myocytes following green fluorescent protein expression. AB - Green fluorescent protein (GFP) and its multiple forms, such as enhanced GFP (EGFP), have been widely used as marker proteins and for tracking purposes in many biological systems, including the heart and cardiac cell systems. Despite some concerns on its toxicity under certain circumstances, GFP remains amongst the most reliable and easy-to-use markers available. Using rat full genome DNA microarrays, we have investigated the broader consequences of adenoviral-driven GFP expression in cardiac myocytes. In our transcriptional profiling analysis, we set a threshold of a twofold change. We removed possible changes resulting from adenoviral infection by comparison with transcriptional profiles of cardiac myocytes with adenoviral-driven expression of an unrelated protein, the kinase MEK. Our analysis revealed changes in the expression of 212 genes. Of these genes, 174 were upregulated and 38 were downregulated following GFP expression. Many of these genes remain unannotated, but an evaluation of those with described functions for their resulting proteins indicated that many were involved in processes, including responses to stimuli/stress and signal transduction. Our analysis thus indicates the broader consequences of GFP expression in altering gene expression profiles in cardiac cells. Care should therefore be taken when using GFP expression as a control in gene expression studies. PMID- 17723105 TI - HMGA1 mediates the activation of the CRYAB promoter by BRG1. AB - alphaB-Crystallin (CRYAB) is a small heat-shock protein that is implicated in many cellular processes, such as transcription and differentiation, as well as pathologic process. It is expressed at high levels in vertebrate eye lens and at low levels in a variety of other cell types. We previously identified CRYAB as a target gene of the chromatin-remodeling SWI/SNF-like Brg or hBrm-associated factors (BAF) complexes. In this report, we identify a 30 bp DNA element required for mediating the activation of CRYAB by brahma-related gene 1 (BRG1). This BRG1 response element is located at the edge of a positioned nucleosome immediately upstream of the transcription initiation site. An AT-rich sequence within this region is bound by the high-mobility group AT-hook 1 (HMGA1) proteins in vitro and in vivo. We demonstrate that the HMGA1 target sequences and HMGA1 proteins are required for the maximal activation of the CRYAB promoter by BRG1. Our data indicate that HMGA1 nonhistone chromatin proteins, the SWI/SNF chromatin remodeling complexes, and sequence-specific transcription factors act together to regulate the expression of the CRYAB gene. PMID- 17723108 TI - Causes and consequences of critical bleeding and mechanisms of blood coagulation. AB - Pharmacists who practice in the critical care setting require a solid background on the causes and consequences of bleeding, as well as the mechanisms of hemostasis. This article provides an overview of these topics. Bleeding and outcomes as a result of surgery and trauma, from medical and pharmacologic causes, and in obstetrics and gynecology are discussed. Patients with brain trauma, those with inherited and acquired bleeding disorders, and patients undergoing therapeutic anticoagulation are addressed, as these are populations at special risk for severe bleeding. Bleeding events as a result of hypothermia, acidosis, and disseminated intravascular coagulation are also discussed, as is the pathophysiology of massive blood loss. Traditional and newer cell-based models of coagulation mechanisms are described and compared. Application of this information in pharmacy practice will help ensure that therapies to manage and arrest blood loss are used appropriately in a wide variety of clinical scenarios. PMID- 17723106 TI - Mechanistic exploration of phthalimide neovascular factor 1 using network analysis tools. AB - Neovascularization is essential for the survival and successful integration of most engineering tissues after implantation in vivo. The objective of this study was to elucidate possible mechanisms of phthalimide neovascular factor 1 (PNF1), a new synthetic small molecule proposed for therapeutic induction of angiogenesis. Complementary deoxyribonucleic acid microarray analysis was used to identify 568 transcripts in human microvascular endothelial cells (HMVECs) that were significantly regulated after 24-h stimulation with 30 muM of PNF1, previously known as SC-3-149. Network analysis tools were used to identify genetic networks of the global biological processes involved in PNF1 stimulation and to describe known molecular and cellular functions that the drug regulated most highly. Examination of the most significantly perturbed networks identified gene products associated with transforming growth factor-beta (TGF-beta), which has many known effects on angiogenesis, and related signal transduction pathways. These include molecules integral to the thrombospondin, plasminogen, fibroblast growth factor, epidermal growth factor, ephrin, Rho, and Ras signaling pathways that are essential to endothelial function. Moreover, real-time reverse transcriptase polymerase chain reaction (RT-PCR) of select genes showed significant increases in TGF-beta-associated receptors endoglin and beta glycan. These experiments provide important insight into the pro-angiogenic mechanism of PNF1, namely, TGF-beta-associated signaling pathways, and may ultimately offer new molecular targets for directed drug discovery. PMID- 17723109 TI - Update on transfusion medicine. AB - Clinical pharmacists often participate on critical care teams that manage patients with bleeding emergencies. Although blood products are usually dispensed from the blood bank and not the pharmacy, pharmacists should be conversant in the language and trends of transfusion medicine, much like they are with other therapeutic agents. Toward that goal, this review provides a concise transfusion medicine tutorial, covering all commonly used blood products, including red blood cells, platelets, fresh frozen plasma, and plasma derivatives such as cryoprecipitate, prothrombin complex concentrates, and albumin. Usage patterns, the rationale for administering the various blood products, and studies that have attempted to determine appropriate criteria for ordering transfusions (transfusion triggers) are discussed. The benefits, risks, and several ongoing controversies that relate to the appropriateness and safety of blood product use are also summarized. PMID- 17723111 TI - Goals of therapy in common bleeding emergencies. AB - Acute hemorrhage is a medical emergency requiring immediate attention, regardless of whether it manifests as blood volume lost and inadequate oxygen delivery, or as a pathologic space-occupying lesion capable of exerting elevated organ damaging pressures. The most commonly encountered and challenging hemorrhagic emergencies to manage include bleeding secondary to traumatic injury, intracranial hemorrhage, severe gastrointestinal bleeding, and diffuse intraoperative bleeding. The critical steps taken to locate, assess, and arrest bleeding in each of these circumstances can take various paths. For all of them, the basic principles of treatment are the same: identify and correct the anatomic source and restore normal hemostatic function. The agents used to accomplish these goals, however, may differ. Several typical clinical scenarios and the evidence-based approaches used to manage such cases are presented. PMID- 17723110 TI - Pharmacologic interventions for the management of critical bleeding. AB - Hospital pharmacists are often consulted for their knowledge about coagulation and therapeutic interventions for the management of critical bleeding. Many pharmacotherapies are available for this purpose, both systemic and topical, and others are in development. These agents and their mechanisms of action are reviewed, and perspectives are provided regarding their use in various clinical settings. Also provided are associated precautions to promote safe use. Current controversies surrounding pharmacotherapeutic agents used to control serious bleeding (e.g., in various types of surgery, trauma, obstetrics, and intracranial hemorrhage) are also discussed. PMID- 17723112 TI - Key concepts in the management of difficult hemorrhagic cases. AB - Goals of hemorrhage management involve promoting coagulation and reducing fibrinolysis to enhance clot formation and stability, and minimizing hemorrhagic expansion to reduce the likelihood of adverse outcomes. The optimal hemostatic regimen to obtain these goals will differ according to the clinical scenario. Two hypothetical cases of patients with hemorrhage are presented that are typical of those encountered by clinical pharmacists who practice in centers that treat trauma or surgical patients or patients in need of emergency or critical care because of serious bleeding. To maximize therapy, the clinician must be aware of how best to clinically apply hemostatic agents, their comparative benefits and disadvantages, and the optimal methods for monitoring their effectiveness and toxicities. PMID- 17723113 TI - Practical considerations when developing guidelines for managing critical bleeding. AB - In the critical care environment, clinicians strive to provide the best treatment possible for patients in desperate need. Such motivation, however, can be a key driver of escalating costs, especially when the use of nonreimbursable therapies goes unchecked or when futile attempts are made to improve outcomes in patients who may not benefit from aggressive management. Proactive intervention in the form of protocols is necessary to guide the use of blood products, coagulation factors, and antifibrinolytic agents. Evidence from clinical trials as well as recommendations from opinion leaders and professional societies should be critically evaluated and used to develop institution-specific protocols. If adopted with multidisciplinary cooperation, such protocols can curb the temptation to rely on anecdotal bedside observations to guide care and treat the patient with critical bleeding. Forming an ad hoc group of an institution's pharmacy and therapeutics committee can be an important step toward this end. The processes that a multidisciplinary group might follow are described, thus providing an idealized example of how pharmacists, working collaboratively with other clinicians and administrators, can be positioned at the center of an institution-wide solution to promote carefully considered, safe, effective, and cost-conscious care. PMID- 17723115 TI - Atherothrombosis risk factors: too many and too little. PMID- 17723117 TI - Neonatal immune tolerance for hemophilia: can we "tolerate" new paradigms for gene therapy trials? PMID- 17723116 TI - A comparison of the associations between seven hemostatic or inflammatory variables and coronary heart disease. AB - BACKGROUND: While meta-analyses of prospective studies have established that plasma levels of several hemostatic variables are associated with the risk of coronary heart disease (CHD), these have been suggested to be acute-phase reactant proteins. This study examines their associations with inflammatory markers [C-reactive protein (CRP) and interleukin-6 (IL-6)] and the effect of adjustment on their associations with CHD risk. METHODS AND RESULTS: In a nested case-control study, 247 CHD cases and 473 controls were matched for age and sex from 10 529 men and women in the Fletcher Challenge cohort. Plasma levels of all hemostatic variables except von Willebrand factor (VWF) and lipoprotein (a) [Lp(a)] showed significant associations with CRP and IL-6. Fibrinogen, VWF, tissue plasminogen activator antigen (t-PA), D-dimer, Lp(a), CRP and IL-6 levels were significantly associated with risk of CHD. After adjustment for conventional risk factors, CRP, D-dimer and IL-6 levels were significantly associated with risk of CHD. On further adjustments for the other six hemostatic and inflammatory variables these associations were reduced, but remained significant for D-dimer and IL-6; odds ratios (95% CI), comparing the highest to lowest third, were 3.10 (1.25-7.67) and 2.79 (1.11-6.99), respectively. CONCLUSION: The associations of plasma levels of some hemostatic variables (fibrinogen, VWF, t-PA and Lp(a); but not fibrin D-dimer) with CHD risk are attenuated when inflammatory markers (CRP and IL-6) as well as conventional risk factors are included in multivariable analyses. D-dimer and IL-6 each have the potential to increase the prediction of CHD, in addition to conventional risk factors. PMID- 17723118 TI - Multiple roles of the endothelial cell protein C receptor. PMID- 17723119 TI - Binding of factor VIIa to the endothelial cell protein C receptor reduces its coagulant activity. AB - BACKGROUND: Endothelial cell protein C receptor (EPCR) binds protein C through its gamma-carboxyglutamic acid (Gla) domain and enhances its thrombin thrombomodulin complex-dependent activation. So far, only protein C/activated protein C has been shown to interact with EPCR. Factor VII (FVII), the coagulation trigger upon tissue factor (TF) interaction, is a serine protease whose Gla domain is highly homologous to the Gla domain of protein C. OBJECTIVES: To characterize the binding of FVII/FVIIa to EPCR and its functional consequences. METHODS AND RESULTS: We demonstrated by surface plasmon resonance (SPR) that FVII/FVIIa binds to EPCR through its Gla domain. At therapeutic concentrations, FVIIa reduced the activation of protein C by 40%. Soluble EPCR (sEPCR) was also able to prolong dose-dependently the clotting time induced by the FVIIa-TF complex. SPR and amidolytic experiments showed that FVIIa is able to interact simultaneously with TF and EPCR, thus ruling out the possibility that the effect of EPCR on clotting time was due to the inhibition of the binding between FVIIa and TF. sEPCR inhibited dose-dependently the activation of FX by the FVIIa-TF complex. Notably, blocking the binding site of EPCR on the endothelial surface increased the generation of FXa 2-fold. CONCLUSIONS: EPCR binds to FVII/FVIIa and inhibits the procoagulant activity of the FVIIa-TF complex. PMID- 17723120 TI - Antiphospholipid syndrome: new light comes from in vivo studies. PMID- 17723121 TI - Role of p38 mitogen-activated protein kinase in antiphospholipid antibody mediated thrombosis and endothelial cell activation. AB - BACKGROUND: The purpose of this study was to examine whether SB 203580, a p38 mitogen-activated protein kinase (MAPK) inhibitor, is effective in reversing the pathogenic effects of antiphospholipid antibodies. METHODS: The adhesion of THP-1 monocytes to cultured endothelial cells (EC) treated with immunoglobulin G (IgG) from a patient with antiphospholipid syndrome (IgG-APS) or control IgG (IgG-NHS) in the presence and absence of SB 203580 was examined. The size of an induced thrombus in the femoral vein, the adhesion of leukocytes to EC of cremaster muscle, tissue factor (TF) activity in carotid artery and in peritoneal macrophages, the ex vivo expression of vascular cell adhesion molecule-1 (VCAM-1) in aorta preparations and platelet aggregation were studied in mice injected with IgG-APS or control IgG-NHS and with or without SB 203580. RESULTS: SB 203580 significantly reduced the increased adhesion of THP-1 to EC in vitro, the number of leukocytes adhering to EC, the thrombus size, the TF activity in carotid arteries and in peritoneal mononuclear cells, and the expression of VCAM-1 in aorta of mice, and completely abrogated platelet aggregation induced by IgG-APS. CONCLUSION: These data suggest that targeting the p38 MAPK pathway may be valuable in designing new therapy modalities for treating thrombosis in patients with APS. PMID- 17723122 TI - Platelet function, antiplatelet therapy and clinical outcomes: to test or not to test? PMID- 17723124 TI - Efficacy of inferior vena cava filters in anticoagulated patients. AB - BACKGROUND AND OBJECTIVES: The benefit of an inferior vena cava (IVC) filter in addition to standard anticoagulation regimens is unknown. METHODS: We examined data for patients who received IVC filters with anticoagulation (AC-Filter) after an episode of venous thromboembolism (VTE) and compared them with data for those who received anticoagulation only (AC-Only). Outcome measures were new pulmonary embolism (PE), recurrent deep vein thrombosis (DVT), and mortality at 90 days and at 5 years. Demographic data included age, gender, and ethnicity/race, prior thromboembolic history, cancer, serum albumin, and time in therapeutic range. In addition, subsets matched for age, gender and race/ethnicity were examined in detail. RESULTS: AC-Filter patients (n = 251), when compared to AC-Only patients (n = 1377), did not differ significantly with regard to gender or cancer status, but white males in general had better outcomes. AC-Filter patients were more likely to have had a previous history of PE or VTE (P < 0.001). In comparison to AC-Only patients, AC-Filter patients had lower mean serum albumin levels (3.1 +/- 0.8 vs. 3.6 +/-0.8 mg dL(-1), P < 0.001) and were older (65 +/- 16.1 years vs. 60 +/- 17.5 years, P < 0.001). After stratification according to previous history of PE or VTE prior to the index VTE event, no differences in the outcome measures of new PE, recurrent DVT or mortality were identified between groups, but patients with a prior history of PE from either group were more likely to have a new PE (hazard ratio 1.9, P < 0.001). CONCLUSIONS: These data suggest that IVC filters may not provide any substantial additional benefit for patients who can tolerate anticoagulant therapy. PMID- 17723123 TI - Different methodologies for evaluating the effect of clopidogrel on platelet function in high-risk coronary artery disease patients. AB - BACKGROUND: Two point-of-care (POC) systems have been recently proposed as rapid tools with which to evaluate residual platelet reactivity (RPR) in coronary artery disease (CAD) patients. OBJECTIVES AND METHODS: We compared Platelet Function Analyzer-100 (PFA-100) closure times (CTs) by collagen/adenosine 5' diphosphate (ADP) (C/ADP CT) cartridge and the VerifyNow P2Y12 Assay (VerifyNow) with light transmission aggregation (LTA) induced by 2 and 10 micromol L(-1) ADP in 1267 CAD patients on dual antiplatelet therapy who underwent percutaneous coronary intervention. We also performed the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay by cytofluorimetric analysis in a subgroup of 115 patients. RESULTS: Cut-off values for identifying RPR were: > or = 54% and > or = 66% for LTA induced by 2 and 10 micromol L(-1) ADP respectively, and > or = 264 P2Y12 Reaction Units (PRU) for VerifyNow. The cut-off for PFA-100 C/ADP CT was > or = 68 s. RPR was detected in 25.1% of patients by 2 mumol L(-1) ADP-induced LTA (ADP-LTA), in 23.2% by 10 micromol L(-1) ADP-LTA, in 24.4% by PFA 100, and in 24.7% by VerifyNow. PFA-100 results did not parallel those obtained with LTA. VerifyNow showed a significant correlation (rho = 0.62, P < 0.001) and significant agreement (k = 0.34, P < 0.001) with LTA induced by 2 micromol L(-1) ADP. The correlation was similar but the agreement was better between VerifyNow and 10 micromol L(-1) ADP-LTA (rho = 0.64, P < 0.0001; k = 0.43, P < 0.001). Significant relationships were found between VASP platelet reactivity index and both ADP-LTA and VerifyNow. PFA-100 C/ADP CT did not significantly correlate with any of the other assays. CONCLUSIONS: Our results show a significant correlation between LTA and VerifyNow but not the PFA-100 C/ADP assay. Clinical validation studies for POC systems are necessary. PMID- 17723125 TI - Fondaparinux combined with intermittent pneumatic compression vs. intermittent pneumatic compression alone for prevention of venous thromboembolism after abdominal surgery: a randomized, double-blind comparison. AB - BACKGROUND: The benefit of combined mechanical and pharmacologic methods for venous thromboembolism prevention after abdominal surgery has not been clearly established. OBJECTIVES: To compare the efficacy and safety of fondaparinux in conjunction with intermittent pneumatic compression vs. intermittent pneumatic compression alone in this context. PATIENTS AND METHODS: This was a randomized, double-blind, placebo-controlled superiority trial. Patients aged at least 40 years undergoing abdominal surgery were randomized to receive either fondaparinux 2.5 mg or placebo s.c. for 5-9 days, starting 6-8 h postoperatively. All patients received intermittent pneumatic compression. The primary efficacy outcome was venous thromboembolism up to day 10. The main safety outcomes were major bleeding and all-cause mortality. Follow-up lasted 32 days. RESULTS: Of the 1309 patients randomized, 842 (64.3%) were evaluable for efficacy. The venous thromboembolism rate was 1.7% (7/424) in the fondaparinux-treated patients and 5.3% (22/418) in the placebo-treated patients (odds ratio reduction 69.8%; 95% confidence interval 27.9-87.3; P = 0.004). Fondaparinux significantly reduced the proximal deep vein thrombosis rate from 1.7% (7/417) to 0.2% (1/424; P = 0.037). Major bleeds occurred in 1.6% (10/635) and 0.2% (1/650) of fondaparinux-treated and placebo treated patients, respectively (P = 0.006), none being fatal or involving a critical organ. By day 32, eight patients (1.3%) receiving fondaparinux and five (0.8%) receiving placebo had died. CONCLUSIONS: In patients undergoing abdominal surgery and receiving intermittent pneumatic compression, fondaparinux 2.5 mg reduced the venous thromboembolism rate by 69.8% as compared to pneumatic compression alone, with a low bleeding risk as compared to placebo. PMID- 17723126 TI - Influence of thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 gene polymorphisms on tissue-type plasminogen activator induced recanalization in ischemic stroke patients. AB - OBJECTIVE: Endogenous resistance to tissue-type plasminogen activator (t-PA) might decrease the benefit of thrombolysis-induced recanalization. Thrombin activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor-1 (PAI-1) are fibrinolysis inhibitors. TAFI removes residues from partially degraded fibrin that in turn eliminates plasminogen binding sites; PAI-1 directly inhibits the activity of t-PA. We aimed to study whether the presence of two common functional polymorphisms of the TAFI and PAI-1 genes influence rates of recanalization of the middle cerebral artery (MCA) among t-PA-treated stroke patients. METHODS AND RESULTS: TAFI and PAI-1 polymorphism determinations were performed by restriction fragment length polymorphism mapping and conventional sequencing in 139 patients with strokes involving the MCA and who received t-PA within 3 h. Recanalization was diagnosed by means of transcranial Doppler. No association was found between PAI-1 4 G/5 G polymorphism and recanalization rate. Dyslipidemia and TAFI Thr325Ile polymorphism were the main variables associated with recanalization resistance by the end of t-PA infusion: odds ratio (OR) 4.1 [95% confidence interval (95% CI) 1.6-10.8, P = 0.003] and OR 5.6 (95% CI 1.2-20, P = 0.031), respectively. The combination of the two polymorphisms doubled the risk of absence of recanalization: OR 11.1 (95% CI 1.4-89.8, P = 0.025). CONCLUSIONS: Polymorphic fibrinolysis inhibitor genes influence t-PA-induced recanalization resistance in ischemic stroke patients, especially when coexisting in the same patient. Efforts to individualize thrombolytic treatments are required. PMID- 17723127 TI - Prevention of catheter-related venous thrombosis with nadroparin in patients receiving chemotherapy for hematologic malignancies: a randomized, placebo controlled study. AB - BACKGROUND: Hemato-oncology patients treated with intensive chemotherapy usually require the placement of a central venous catheter (CVC). CVCs are frequently complicated by catheter-related central venous thrombosis (CVT), which has been associated with an increased risk of pulmonary embolism and catheter-related infection. OBJECTIVES: To determine the efficacy and safety of thromboprophylaxis with s.c. low-molecular-weight heparin (nadroparin) administered once daily in a randomized placebo-controlled, double-blind trial in patients with hematologic malignancies. PATIENTS AND METHODS: Consecutive patients with hematologic malignancies requiring intensive chemotherapy including autologous stem cell transplantation were eligible. The patients were randomized to receive nadroparin 2850 antifactor Xa units once daily or placebo s.c. for 3 weeks. Venography was performed on day 21 after CVC insertion. Secondary outcomes were bleeding and catheter-related infection. RESULTS: In total, 113 patients were randomized to nadroparin or placebo, and 87 patients (77%) underwent venography. In total, 11 venographically proven catheter-related CVTs were diagnosed. The frequency of catheter-related CVT was not significantly different between study groups, namely four catheter-related CVTs in the placebo group [9%; 95% CI: 0.002-0.16] vs. seven catheter-related CVTs in the nadroparin group (17%; 95% CI: 0.06-0.28). In addition, no difference in the incidence of catheter-related infection or bleeding was observed between the groups. CONCLUSION: This study showed that the actual risk for catheter-related CVT in patients with hematologic malignancies is lower than suggested in earlier studies in cancer patients. Although prophylactic administration of nadroparin appeared to be safe in this group of patients with a high risk of bleeding, it cannot be recommended for the prevention of catheter related CVT or catheter-related infection in patients with hematologic malignancies. PMID- 17723128 TI - Effect of leg exercises on popliteal venous blood flow during prolonged immobility of seated subjects: implications for prevention of travel-related deep vein thrombosis. AB - BACKGROUND: Venous stasis is an important contributing factor in the development of travel-related deep vein thrombosis. This study examined factors affecting popliteal venous blood flow in order to determine the most effective exercise regimen to prevent venous stasis. METHODS: Twenty-one healthy subjects were randomly assigned to various activities over a 9-week period. Subjects remained seated throughout the investigation and 3660 duplex ultrasound examinations were performed by a single examiner using a SonoSite 180 Plus handheld ultrasound. Baseline popliteal vein blood flow velocity, cross-sectional area and volume flow in subjects sitting motionless were assessed in the first 3 weeks.The remaining 6 weeks involved subjects performing airline-recommended activities, foot exercises, foot exercises against moderate resistance and foot exercises against increased resistance in order to determine the most beneficial method for enhancing popliteal venous flow. Sitting with feet not touching the floor and the effect of sleeping were also assessed. RESULTS: The median age of the subjects was 22 years (range: 18-25.5 years), height 171 cm (162.5-180.5 cm) and body mass index 25.3 kg m(-2) (23.2-26.3 kg m(-2)). Blood volume flow in the popliteal vein was reduced by almost 40% with immobility of seated subjects and by almost 2-fold when sitting motionless with feet not touching the floor. Foot exercises against increased resistance positively enhanced volume flow (P < 0.0001). CONCLUSION: Leg exercise regimens enhanced popliteal venous flow during prolonged immobility of seated subjects, reinforcing the importance of regular leg movement to prevent venous stasis during prolonged sitting, such as in long-distance travel. PMID- 17723129 TI - The plasma kallikrein-kinin system and risk of cardiovascular disease in men. AB - BACKGROUND: The plasma kallikrein-kinin system (PKKS) has been implicated in cardiovascular disease, but activation of the PKKS has not been directly probed in individuals at risk of coronary heart disease (CHD) or stroke. OBJECTIVE: To determine the involvement of the PKKS, including factor XI, in cardiovascular disease occurring in a nested case-control study from the Second Northwick Park Heart Study (NPHS-II). METHODS AND RESULTS: After a median follow-up of 10.7 years, 287 cases of CHD and stroke had been recorded and 542 age-matched controls were selected. When FXIIa-C1 esterase inhibitor (C1-inhibitor) concentrations were divided into tertiles (lowest tertile as reference), the odds ratios (ORs) at 95% CIs for CHD were 0.52 (0.34-0.80) in the middle tertile and 0.73 (0.49 1.09) in the highest tertile (P = 0.01 for the overall difference; P = 0.01 for CHD and stroke combined). For kallikrein-C1-inhibitor complexes, the ORs for stroke were 0.29 (0.12-0.72) and 0.67 (0.30-1.52) in the middle and high tertiles, respectively (P = 0.02). FXIIa-C1-inhibitor and kallikrein-C1-inhibitor complexes were negatively related to smoking and fibrinogen (P < 0.005). FXIa inhibitor complexes correlated strongly with FXIIa-inhibitor complexes. CONCLUSIONS: Lower levels of inhibitory complexes of the PKKS enzymes and particularly of FXIIa contribute to the risk of CHD and stroke in middle-aged men. This observation supports the involvement of the PKKS in atherothrombosis. PMID- 17723130 TI - Randomized, prospective clinical trial of recombinant factor VIIa for secondary prophylaxis in hemophilia patients with inhibitors. AB - BACKGROUND: Hemophilic patients with factor VIII (FVIII) and FIX inhibitors suffer from frequent bleeding episodes and reduced quality of life. OBJECTIVES: To evaluate whether secondary prophylaxis with activated recombinant factor VII (rFVIIa) can safely and effectively reduce bleeding frequency as compared to conventional on-demand therapy. METHODS: Thirty-eight male patients entered a 3 month preprophylaxis period to confirm high baseline bleeding frequency (mean > or = 4 bleeds per month). Twenty-two patients were randomized 1:1 to receive daily rFVIIa prophylaxis with either 90 or 270 microg kg(-1) for 3 months, followed by a 3-month postprophylaxis period. RESULTS: Bleeding frequency was reduced by 45% and 59% during prophylaxis with 90 and 270 microg kg(-1), respectively (P < 0.0001); however, there was no significant difference detected between doses. The majority of this reduction was maintained during the postprophylaxis period. Although all types of bleed were similarly reduced, the effect was most pronounced for spontaneous joint bleeds. Patients reported significantly fewer hospital admissions and days absent from work/school during prophylaxis as compared to the preprophylaxis period. No thromboembolic events were reported during prophylaxis. CONCLUSION: Clinically relevant reductions in bleeding frequency during prophylaxis as compared to conventional on-demand therapy were achieved without raising safety concerns. These results provide evidence for the concept of secondary rFVIIa prophylaxis in inhibitor patients with frequent bleeds. PMID- 17723131 TI - A collaborative study to establish the 1st International Standard for factor XIII plasma. AB - BACKGROUND: An international collaborative study, involving 23 laboratories, was carried out, under the auspices of the FXIII Standardization Working Party (SWP), to calibrate the 1st International Standard (IS) for factor XIII (FXIII) plasma. METHODS: Potency estimates for the proposed candidate FXIII plasma (preparation Y: NIBSC code 02/206) were calculated relative to locally collected normal plasma pools (pool N), for both FXIII activity and antigen levels. RESULTS: Estimates of FXIII activity potency for preparation Y showed good agreement between laboratories, with an interlaboratory geometric coefficient of variation (GCV) of 11.5% and a mean value of 0.91 U mL(-1). Furthermore, there was a negligible difference in potencies by two commercially available methods, the potencies differing only by approximately 1%. Estimates of FXIII antigen (A(2)B(2) complex) potency for preparation Y showed good agreement between laboratories, with an interlaboratory GCV of 16.3% and a mean value of 0.93 U mL(-1). Accelerated degradation studies showed that the proposed standard is very stable, with a predicted loss of activity (and antigen) per year of< 0.06% at the recommended storage temperature of -20 degrees C. CONCLUSIONS: The suitability and potency of preparation Y were considered by the participants, members of the ISTH/SSC FXIII Subcommittee, the Scientific and Standardization Committee and the SWP. Following their approval, preparation Y was proposed to and accepted by the Expert Committee on Biological Standardization of the World Health Organization to be the 1st IS for FXIII plasma with an activity potency of 0.91 IU per ampoule and an antigen potency of 0.93 IU per ampoule. PMID- 17723132 TI - A genetic basis for the interrelation of coagulation factors. AB - BACKGROUND: Evidence found in the literature for a strong correlation between coagulation factors suggests that single genes might influence the plasma concentrations of multiple coagulation factors (i.e. pleiotropically acting genes). OBJECTIVE: To determine whether there is a genetic basis for the correlation among coagulation factors by assessing the heritability of interrelated coagulation factors. PATIENTS/METHODS: We performed principal components analysis, and subsequently variance components analysis, to estimate the heritability of principal components of coagulation factors in family members of a large French-Canadian kindred. RESULTS: Four clusters were identified by principal components analysis in 200 family members who did not carry the protein C 3363C mutation. Cluster 1 consisted of prothrombin, factor VII (FVII), FIX, FX and protein S; cluster 2 consisted of FV, FIX, protein C and tissue factor pathway inhibitor; cluster 3 consisted of FVIII and von Willebrand factor; and cluster 4 consisted of antithrombin, protein C and FVII. The heritability of the principal components estimated by variance components analysis was, respectively, 37%, 100%, 37%, and 37%. CONCLUSION: Our findings support the hypothesis that genes can influence plasma levels of interrelated coagulation factors. PMID- 17723133 TI - Systemic administration of anti-urokinase plasminogen activator receptor monoclonal antibodies induces hepatic fibrin deposition in tissue-type plasminogen activator deficient mice. AB - BACKGROUND: Degradation of extracellular matrix proteins, such as fibrin, is pivotal to tumor invasion. Inhibition of the interaction between urokinase plasminogen activator (u-PA) and its receptor (u-PAR), and hence pro-u-PA activation, is an attractive approach to anti-invasive cancer therapy. A number of inhibitors exist for the human system, but because of species specificity none of these are efficient in mice. We have recently generated an inhibitory monoclonal antibody (mAb) against mouse u-PAR (mR1) by immunization of u-PAR deficient mice. OBJECTIVES: To evaluate the effect of mR1 in vivo in a physiological setting sensitive to deregulated fibrinolysis, we have administered mR1 systemically and quantitated the effect on liver fibrin accumulation. METHODS: Wild-type and tissue-type plasminogen activator (t-PA) deficient mice were administered with mR1, or control antibody, during 6 weeks. Thereafter, the livers were retrieved and the amount of liver fibrin measured by unbiased morphometrical analysis of immunofluorescence signal. RESULTS: Systemic administration of mR1 caused significantly increased fibrin signal in anti-u-PAR treated t-PA-deficient mice compared to mock-treated, which mimics the phenotype of u-PAR;t-PA double-deficient mice. Fibrin and fibronectin accumulated within the sinusoidal space and was infiltrated by inflammatory cells. Analysis of small and rare hepatic fibrin plaques observed in t-PA-deficient mice showed infiltrating macrophages that, contrary to surrounding Kuppfer cells, expressed u PAR. CONCLUSION: We show that u-PAR-expressing macrophages are involved in cell mediated fibrinolysis of liver fibrin deposits, and that the antimouse-u-PAR mAb is effective in vivo and thus suited for studies of the effect of targeting the u PA/u-PAR interaction in mouse cancer models. PMID- 17723134 TI - Proteomic analysis of platelet alpha-granules using mass spectrometry. AB - BACKGROUND: Platelets have three major types of secretory organelles: lysosomes, dense granules, and alpha-granules. alpha-Granules contain several adhesive proteins involved in hemostasis, as well as glycoproteins involved in inflammation, wound healing, and cell-matrix interactions. This article represents the first effort to define the platelet alpha-granule proteome using mass spectrometry (MS). METHODS: We prepared a subcellular fraction enriched in intact alpha-granules from human platelets using sucrose gradient ultracentrifugation. alpha-Granule proteins were separated and identified using sodium dodecylsulfate polyacrylamide gel electrophoresis and liquid chromatography-tandem MS. RESULTS: In the sucrose fraction enriched in alpha granules, we identified 284 non-redundant proteins, 44 of which appear to be new alpha-granule proteins, on the basis of a literature review. Immunoelectron microscopy confirmed the presence of Scamp2, APLP2, ESAM and LAMA5 in platelet alpha-granules for the first time. We identified 65% of the same proteins that were detected in the platelet releasate (J. A. Coppinger et al. [Blood 2004;103: 2096-104]) as well as additional soluble and membrane proteins. Our method provides a suitable tool for analyzing the granule proteome of patients with storage pool deficiencies. PMID- 17723135 TI - Characterization of the interaction between von Willebrand factor and osteoprotegerin. AB - BACKGROUND AND OBJECTIVE: Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor superfamily, plays an important role in bone remodeling and is also involved in vascular diseases. OPG is physically associated with von Willebrand factor (VWF), a glycoprotein involved in primary hemostasis, within the Weibel-Palade bodies (WPBs) of endothelial cells and in plasma. The present study aimed to elucidate the molecular mechanisms underlying the interaction between OPG and VWF. METHODS AND RESULTS: In a solid-phase binding assay, VWF was able to bind specifically to OPG in a calcium-dependent manner. This interaction displayed strong pH dependence with optimal binding occurring at pH 6.5 and was severely impaired by chloride-ion concentrations above 40 mm. Using a series of purified VWF derivatives the functional site that supports VWF interaction with OPG was localized on its Al domain. Fluorescence microscopy on human umbilical vein endothelial cells showed co-localization of VWF and OPG in WPBs. When secretion was induced, OPG remained associated with VWF in extracellular patches of release under biochemical conditions found in blood plasma. CONCLUSIONS: Our observations demonstrate the existence of an interactive site for OPG within the VWF A1-domain. This study established that the optimal biochemical parameters allowing a complex formation between VWF and OPG are those thought to prevail in the trans-Golgi network. These conditions would allow VWF to act as a cargo targeting OPG to WPBs. Finally, blood environments appear suitable to preserve the complex, which may participate in vascular injury, arterial calcification and inflammation. PMID- 17723137 TI - Scott syndrome dogs have impaired coated-platelet formation and calcein-release but normal mitochondrial depolarization. PMID- 17723136 TI - Two novel monoclonal antibodies to VWFA3 inhibit VWF-collagen and VWF-platelet interactions. AB - BACKGROUND: The interaction of collagen-von Willebrand factor (VWF)-GPIb is essential for platelet adhesion, especially under high shear conditions. VWF, which acts as a bridge between platelets and exposed subendothelium, interacts with collagen through its A3 domain, which is a new target for the antithrombotic agent. OBJECTIVE: To develop functional blockers that specifically inhibit VWF dependent adhesion of platelets to collagen under high shear stress. METHODS: To develop murine antihuman VWF A3 monoclonal antibodies (mAbs) by standard hybridoma technology, and characterize their abilities to block interactions between VWF A3 and collagen as well as platelet function. RESULTS: Thirty anti VWF-A3 mAbs were obtained. Among them, two mAbs, designated as SZ-123 and SZ-125, were found to inhibit VWF-collagen type III interaction. SZ-123 and SZ-125 inhibited the binding of purified human VWF (1.5 or 3 mug mL(-1)) to human placenta collagen type III (IC(50) = 0.07 +/- 0.02 and 0.15 +/- 0.03 mug mL(-1), respectively) or to calf skin collagen type III (IC(50) = 0.48 +/- 0.06 and 0.51 +/- 0.07 mug mL(-1), respectively) coated on plates. Under flow shear condition (1000 s(-1)), SZ-123 and SZ-125 inhibited platelet adhesion on human placenta collagen- or calf skin collagen-coated surfaces. Both mAbs also inhibited platelet aggregation induced by ristocetin, botrocetin or bovine plasma. CONCLUSIONS: SZ-123 and SZ-125 inhibited VWF-collagen and VWF-platelet interactions. PMID- 17723138 TI - Effect of daptomycin on prothrombin time and the requirement for outlier exclusion in International Sensitivity Index calibration of thromboplastin. PMID- 17723139 TI - Mg(2+) binding to the Gla domain of factor X influences the interaction with tissue factor. PMID- 17723140 TI - Current practise of testing for inherited thrombophilia. PMID- 17723141 TI - Influence of argatroban on coagulation parameters in heparin-induced thrombocytopenia patients after cardiothoracic surgery. PMID- 17723142 TI - Altered fibrin clot structure in patients with advanced coronary artery disease: a role of C-reactive protein, lipoprotein(a) and homocysteine. PMID- 17723143 TI - Outcome of the subsequent pregnancy after a first loss in women with factor V Leiden or prothrombin 20210A mutation: a rebuttal. PMID- 17723146 TI - Modular co-evolution of metabolic networks. AB - BACKGROUND: The architecture of biological networks has been reported to exhibit high level of modularity, and to some extent, topological modules of networks overlap with known functional modules. However, how the modular topology of the molecular network affects the evolution of its member proteins remains unclear. RESULTS: In this work, the functional and evolutionary modularity of Homo sapiens (H. sapiens) metabolic network were investigated from a topological point of view. Network decomposition shows that the metabolic network is organized in a highly modular core-periphery way, in which the core modules are tightly linked together and perform basic metabolism functions, whereas the periphery modules only interact with few modules and accomplish relatively independent and specialized functions. Moreover, over half of the modules exhibit co-evolutionary feature and belong to specific evolutionary ages. Peripheral modules tend to evolve more cohesively and faster than core modules do. CONCLUSION: The correlation between functional, evolutionary and topological modularity suggests that the evolutionary history and functional requirements of metabolic systems have been imprinted in the architecture of metabolic networks. Such systems level analysis could demonstrate how the evolution of genes may be placed in a genome scale network context, giving a novel perspective on molecular evolution. PMID- 17723147 TI - PROUD: effects of preoperative long-term immunonutrition in patients listed for liver transplantation. AB - BACKGROUND: Patients with end stage liver disease are characteristically malnourished which is associated with poor outcome. Formulas enriched with arginine, omega-3 fatty acids, and nucleotides, "immunonutrients", potentially improve their nutritional status. This study is designed to evaluate the clinical outcome of long-term "immunonutrition" of patients with end-stage liver disease while on the waiting list for liver transplantation. METHODS/DESIGN: A randomized controlled double blind multi-center clinical trial with two parallel groups comprising a total of 142 newly registered patients for primary liver transplantation has been designed to assess the safety and efficacy of the long term administration of ORAL IMPACT, an "immunonutrient" formula, while waiting for a graft. Patients will be enrolled the day of registration on the waiting list for liver transplantation. Study ends on the day of transplantation. Primary endpoints include improved patients' nutritional and physiological status, as measured by mid-arm muscle area, triceps skin fold thickness, grip strength, and fatigue score, as well as patients' health related quality of life. Furthermore, patients will be followed for 12 postoperative weeks to evaluate anabolic recovery after transplantation as shown by reduced post-transplant mechanical ventilation, hospital stay, wound healing, infectious morbidities (pneumonia, intraabdominal abscess, sepsis, line sepsis, wound infection, and urinary tract infection), acute and chronic rejection, and mortality. DISCUSSION: Formulas enriched with arginine, omega-3 fatty acids, and nucleotides have been proven to be beneficial in reducing postoperative infectious complications and length of hospital stay among the patients undergoing elective gastrointestinal surgery. Possible mechanisms include downregulation of the inflammatory responses to surgery and immune modulation rather than a sole nutritional effect. TRIAL REGISTRATION: ClinicalTrials.gov NCT00495859. PMID- 17723148 TI - Activity and Life After Survival of a Cardiac Arrest (ALASCA) and the effectiveness of an early intervention service: design of a randomised controlled trial. AB - BACKGROUND: Cardiac arrest survivors may experience hypoxic brain injury that results in cognitive impairments which frequently remain unrecognised. This may lead to limitations in daily activities and participation in society, a decreased quality of life for the patient, and a high strain for the caregiver. Publications about interventions directed at improving quality of life after survival of a cardiac arrest are scarce. Therefore, evidence about effective rehabilitation programmes for cardiac arrest survivors is urgently needed. This paper presents the design of the ALASCA (Activity and Life After Survival of a Cardiac Arrest) trial, a randomised, controlled clinical trial to evaluate the effects of a new early intervention service for survivors of a cardiac arrest and their caregivers. METHODS/DESIGN: The study population comprises all people who survive two weeks after a cardiac arrest and are admitted to one of the participating hospitals in the Southern part of the Netherlands. In a two-group randomised, controlled clinical trial, half of the participants will receive an early intervention service. The early intervention service consists of several consultations with a specialised nurse for the patient and their caregiver during the first three months after the cardiac arrest. The intervention is directed at screening for cognitive problems, provision of informational, emotional and practical support, and stimulating self-management. If necessary, referral to specialised care can take place. Persons in the control group will receive the care as usual. The primary outcome measures are the extent of participation in society and quality of life of the patient one year after a cardiac arrest. Secondary outcome measures are the level of cognitive, emotional and cardiovascular impairment and daily functioning of the patient, as well as the strain for and quality of life of the caregiver. Participants and their caregivers will be followed for twelve months after the cardiac arrest.A process evaluation will be performed to gain insight into factors that might have contributed to the effectiveness of the intervention and to gather information about the feasibility of the programme. Furthermore, an economic evaluation will be carried out to determine the cost-effectiveness and cost-utility of the intervention. DISCUSSION: The results of this study will provide evidence on the effectiveness of this early intervention service, as well as the cost effectiveness and its feasibility. TRIAL REGISTRATION: Current Controlled Trials [ISRCTN74835019]. PMID- 17723149 TI - Health behaviors and risk factors in those who use complementary and alternative medicine. AB - BACKGROUND: Surveys have generally found that individuals more likely to use complementary and alternative medicine are female, live in the western United States, are likely to have a health complaint, and have a higher socioeconomic status than do nonusers. What is not known is the extent to which those who use complementary and alternative medicine also engage in positive health behaviors, such as smoking cessation or increased physical activity and/or exhibit fewer health risk factors such as obesity. This has been identified as a key research question in a recent Institute of Medicine report. In the present study we sought to determine whether the use of complementary and alternative medicine is associated with health behaviors or risk factors known to impact on health status. METHODS: The current study is a cross-sectional regression analysis using data from the 2002 National Health Interview Survey. Data were collected in person from 31,044 adults throughout the 50 states and the District of Columbia. RESULTS: After controlling for a range of other factors, we found that engaging in leisure-time physical activity, having consumed alcohol in one's life but not being a current heavy drinker, and being a former smoker are independently associated with the use of CAM. Obese individuals are slightly less likely to use CAM than individuals with a healthy body-mass index. No significant associations were observed between receipt of an influenza vaccine and CAM use. CONCLUSION: Those engaging in positive health behaviors and exhibiting fewer health risk factors are more likely to use CAM than those who forgo positive health behaviors or exhibit more health risk factors. The fact that users of CAM tend to pursue generally healthy lifestyles suggests that they may be open to additional recommendations toward optimizing their health. PMID- 17723150 TI - High-efficiency protein expression in plants from agroinfection-compatible Tobacco mosaic virus expression vectors. AB - BACKGROUND: Plants are increasingly being examined as alternative recombinant protein expression systems. Recombinant protein expression levels in plants from Tobacco mosaic virus (TMV)-based vectors are much higher than those possible from plant promoters. However the common TMV expression vectors are costly, and at times technically challenging, to work with. Therefore it was a goal to develop TMV expression vectors that express high levels of recombinant protein and are easier, more reliable, and more cost-effective to use. RESULTS: We have constructed a Cauliflower mosaic virus (CaMV) 35S promoter-driven TMV expression vector that can be delivered as a T-DNA to plant cells by Agrobacterium tumefaciens. Co-introduction (by agroinfiltration) of this T-DNA along with a 35S promoter driven gene for the RNA silencing suppressor P19, from Tomato bushy stunt virus (TBSV) resulted in essentially complete infection of the infiltrated plant tissue with the TMV vector by 4 days post infiltration (DPI). The TMV vector produced between 600 and 1200 micrograms of recombinant protein per gram of infiltrated tissue by 6 DPI. Similar levels of recombinant protein were detected in systemically infected plant tissue 10-14 DPI. These expression levels were 10 to 25 times higher than the most efficient 35S promoter driven transient expression systems described to date. CONCLUSION: These modifications to the TMV based expression vector system have made TMV vectors an easier, more reliable and more cost-effective way to produce recombinant proteins in plants. These improvements should facilitate the production of recombinant proteins in plants for both research and product development purposes. The vector should be especially useful in high-throughput experiments. PMID- 17723151 TI - Regions of Diversity 8, 9 and 13 contribute to Streptococcus pneumoniae virulence. AB - BACKGROUND: Streptococcus pneumoniae is the leading cause of community-acquired pneumonia. Previously, using comparative genomic analyses, 13 regions of genomic plasticity have been identified in the S. pneumoniae genome. These "Regions of Diversity" (RDs) accounted for half the genomic variation observed amongst all pneumococci tested, moreover, were determined to encode a variety of putative virulence factors. To date, genes within 5 RDs have been unequivocally demonstrated to contribute to S. pneumoniae virulence. It is unknown if the remaining RDs also contribute to virulence. RESULTS: Using allelic exchange, we created S. pneumoniae mutants that were deficient in RD2, 5, 7, 8, 9, 12 and 13. Mutants deficient in RD8, 9 and 13 were attenuated in a mouse model of disease. RD8 is 40,358 nucleotides in length and encodes 37 genes. Using a panel of isogenic mutants, we determined that RD8b3 is the operon within RD8 that is responsible for virulence. Mice infected with mutants deficient in RD8, RD8b3, RD9 and RD13 had significantly less bacteria in the blood two days after intranasal challenge and improved survival over time versus mice infected with wild type. In all instances mutants colonized the nasopharynx at levels equivalent to wild type. CONCLUSION: Genes within RD1, 3, 4, 6, and 10 have previously been shown to contribute to virulence. This study demonstrates that genes within RD8, 9 and 13 also contribute to virulence. The ability of mutants deficient in RD2, 5, 7, 8, 9, 12, and 13 to colonize the nasopharynx indicates that genes within these RDs are not required for asymptomatic carriage. Nonetheless, the observation that mutants deficient in RD8b3, 9 and 13 are attenuated indicates that genes within these loci are necessary for spread of the bacteria beyond the nasopharynx to normally sterile sites. PMID- 17723152 TI - Strong decline in female sterilization rates in Norway after the introduction of a new copayment system: a registry based study. AB - BACKGROUND: January 1, 2002, copayment for outpatient female sterilization in Norwegian public hospitals increased from 33 euro to 750 euro after a revision of the health care system. The aim of the present study was to investigate the effect of the new copayment system on female sterilization epidemiology. METHODS: We retrieved data on all female sterilizations 1999-2005 (N = 23 1333) from the Norwegian Patient Register, an administrative register to which it is mandatory for all hospitals to report. Sterilizations with diagnostic codes indicative of vaginal delivery, caesarean section, spontaneous abortion, ectopic pregnancy, and termination of pregnancy were analyzed separately. All other sterilizations were defined as "interval sterilization". RESULTS: An abrupt fall in female sterilization was observed after the raise in copayment. Age-adjusted incidence rates dropped from 6.3-6.8 per 1000 women in 1999-2001 to 2.2-2.3 per 1000 women during 2002-2005. Interval sterilizations dropped to 25% of the previous level after the rise in copayment while sterilizations in conjunction with caesarean section and postpartum sterilization remained constant. CONCLUSION: For many Norwegian women seeking contraception, sterilization is no longer an available alternative. PMID- 17723156 TI - Comparative optimism in the spontaneous generation of future life-events. AB - We examined whether comparative optimism characterizes the events people generate when they describe their future. In contrast to previous studies in which participants estimated the likelihoods of experimenter-generated events, our participants freely listed important events they believed were possible in their future versus the average person's future. They also provided desirability ratings, controllability ratings, and likelihood estimates for these self generated events. Participants listed more desirable and fewer undesirable events in their future than in the average person's future. These differences were stronger for controllable than uncontrollable events. Comparative optimism was also observed in participants' ratings of the likelihood of positive and negative events. Taken together, these findings suggest that a comparative optimism characterizes future expectations about spontaneously generated events as well as the pre-selected events sampled in previous studies. PMID- 17723155 TI - Health Related Quality of Life, an appropriate indicator to assess the impact of morbidity management and disability prevention activities towards elimination of lymphatic filariasis. AB - BACKGROUND: Lymphatic filariasis has been identified as one of the six diseases that can be potentially eliminated. Global programme to eliminate lymphatic filariasis has been launched, applying principal strategies of mass drug administration to interrupt transmission and morbidity management to prevent disability. The strategy for mass drug administration has been clearly laid out and guidelines have been well documented for implementation, monitoring and evaluation of the programme but such a guideline is warranted for morbidity management and disability prevention activities. DISCUSSION: Health Related Quality of Life, a multidimensional construct referring to patients' perceptions of the impact of disease and treatment on their physical, psychological and social function and well being is crucial in the evaluation of health care interventions. Lymphatic filariasis has a wide clinical spectrum and disability is more pronounced in the advanced stages of lymphoedema and hydrocele. Since the advanced stages of lymphoedema are not reversible, morbidity management and disability prevention activities can lessen the disabilities due to secondary infections and there by improve the quality of life of the patient. Thus, an improvement in quality of life is considered to be important as a primary outcome in the determination of therapeutic benefit. Therefore it can be used as an indicator to assess the impact of morbidity management and disability prevention activities in global programme to eliminate lymphatic filariasis. SUMMARY: Disease specific Health Related Quality of Life instrument can be used to measure the longitudinal changes in quality of life of patients following the intervention. High responsiveness, clinical relevance to patients and its sensitiveness to detect small changes are the merits of disease specific instrument. Morbidity management and disability prevention activities under filariasis elimination programme aim at improving the quality of life of patients with irreversible manifestations. Therefore there is an urgent need to develop an instrument to assess the health related quality of life, specific for lymphatic filariasis by incorporating all the difficulties and problems caused to patients by the disease in the physical, mental and social domains of health. PMID- 17723153 TI - Usefulness of C-reactive protein in monitoring the severe community-acquired pneumonia clinical course. AB - BACKGROUND: The aim of the present study was to evaluate the C-reactive protein level, the body temperature and the white cell count in patients after prescription of antibiotics in order to describe the clinical resolution of severe community-acquired pneumonia. METHODS: A cohort of 53 consecutive patients with severe community-acquired pneumonia was studied. The C-reactive protein levels, body temperature and white cell count were monitored daily. RESULTS: By day 3 a C-reactive protein level 0.5 times the initial level was a marker of poor outcome (sensitivity, 0.91; specificity, 0.59). Patients were divided according to their C-reactive protein patterns of response to antibiotics, into fast response, slow response, nonresponse, and biphasic response. About 96% of patients with a C-reactive protein pattern of fast response and 74% of patients with a slow response pattern survived, whereas those patients with the patterns of nonresponse and of biphasic response had a mortality rate of 100% and 33%, respectively (P < 0.001). On day 3 of antibiotic therapy, a decrease in C reactive protein levels by 0.31 or more from the previous day's level was a marker of good prognosis (sensitivity, 0.75; specificity, 0.85). CONCLUSION: Daily C-reactive protein measurement after antibiotic prescription is useful in identification, as early as day 3, of severe community-acquired pneumonia patients with poor outcome. The identification of the C-reactive protein pattern of response to antibiotic therapy was useful in the recognition of the individual clinical course, either improving or worsening, as well as the rate of improvement, in patients with severe community-acquired pneumonia. PMID- 17723157 TI - The Rookwood Driving Battery: normative older adult performance. AB - OBJECTIVES: The current study aimed to obtain older adult normative data on a neuropsychological battery in relation to functions underlying driving ability. The effect of age on performance on the battery was previously unknown; normative data revision was necessary to enable more appropriate use of the battery with older clients. DESIGN: Cross-sectional cohort study. METHODS: Volunteers were sought from healthy older people living independently in the community to complete the Rookwood Driving Battery. A group of 202 volunteers above the age of 70 were recruited from local social groups to complete the battery. Of these, 184 completed a screening test of cognitive integrity (Mini Mental State Examination, MMSE). The age ranged from 70 to 96 (mean age=81 years, SD=5.438). In the total sample, 155 (77%) were females. RESULTS: Results of the MMSE indicated that 161 (87.5%) of the group fell above a cut-off (25/30) typically used in epidemiological studies to identify age-related cognitive decline. Of these cognitively intact volunteers, performance was marked by higher battery error scores (mean=5.12, SD=3.75) than those observed in an earlier normative study using younger volunteers below 70 years of age (mean=1.41, SD=1.87). The two age groups differed significantly on all 10 battery subtests; in all cases the level of significance was .002 or less; for nine subtests, significance fell below .001. In the 'intact' older group, battery performance was observed to be closely related to score on the MMSE, a test of general cognitive integrity (r=.558, p=.01). CONCLUSIONS: Performance on the Rookwood Battery differs for the over 70s and under 70s. The authors suggest essential modifications in its use with older people. PMID- 17723158 TI - Use of almotriptan in triptan-experienced and triptan-naive patients. AB - OBJECTIVE: To evaluate the efficacy of oral almotriptan 12.5 mg as an acute treatment for migraine with a focus on triptan-experienced versus triptan-naive patients. RESEARCH DESIGN AND METHODS: Four recent Almirall-sponsored clinical trials of oral almotriptan 12.5 mg in acute migraine, in which data regarding previous acute therapy were collected, are reviewed. The results and conclusions are limited by the open-label and post hoc design of some of these trials and analyses. RESULTS: In two trials, almotriptan 12.5 mg was used to treat migraine sufferers who were dissatisfied with or were receiving inadequate results with their previous therapy. One of these trials enrolled only patients whose dissatisfaction with their current therapy was confirmed by a validated questionnaire; the other looked at almotriptan 12.5 mg efficacy in patients with previous poor response to sumatriptan. In the other two trials, patients had been achieving satisfactory results with their migraine therapy; one was a randomized, double-blind clinical trial of almotriptan 12.5 mg and zolmitriptan 2.5 mg, the other was an open-label almotriptan 12.5 mg satisfaction trial. Almotriptan 12.5 mg is shown to be effective, well-tolerated, and preferred to previous agents in both patients who were satisfied with, and those who were dissatisfied with, their previous therapy. CONCLUSIONS: Almotriptan should, therefore, not only be considered as first-line therapy for acute migraine but should also be considered for patients who are not satisfied with or not receiving optimal relief from their current acute therapy. PMID- 17723159 TI - A randomised, double-blind, placebo-controlled trial of a herbal medicinal product containing Tropaeoli majoris herba (Nasturtium) and Armoraciae rusticanae radix (Horseradish) for the prophylactic treatment of patients with chronically recurrent lower urinary tract infections. AB - OBJECTIVES: The aim of this study was to verify the efficacy and safety of a herbal medicinal product containing Tropaeoli majoris herba and Armoraciae rusticanae radix in the prophylactic treatment of chronically recurrent urinary tract infections (UTIs), and to test whether the medicinal product decreases the incidence of relapses over the study period. METHODS: A total of 219 adults aged between 18 and 75 years were screened and 174 patients enrolled. Of these 174 patients, a group of 45 patients were screening failures. Patients were randomised to receive either the study drug or placebo twice daily for 90 days. A UTI is confirmed by defined symptoms together with a laboratory result. The diagnosis of a new episode of a recurrent UTI included urine analysis from a central laboratory. The primary efficacy criterion - the number of recurrent UTIs over the study period - was tested between the treatment groups. RESULTS: For the per-protocol population, the mean number of recurrent UTIs in the study period was 0.43 versus 0.77 for the placebo group. This result is statistically significant (p = 0.035). A total of 36 patients in the test group and 37 patients in the placebo group reported adverse events. Two serious adverse events were reported in the placebo group and one serious adverse event in the treatment group (not associated with the study medication). CONCLUSION: This randomised, double-blind, placebo-controlled trial demonstrates the efficacy and safety of the herbal medicinal product Angocin Anti-Infekt N* in the prophylactic treatment of chronically recurrent UTIs. PMID- 17723160 TI - Azelastine hydrochloride: a review of pharmacology, pharmacokinetics, clinical efficacy and tolerability. AB - INTRODUCTION: Azelastine hydrochloride (Astelin) nasal spray 0.1% solution is a second-generation intranasal antihistamine available in the US for treatment of both seasonal allergic rhinitis (SAR) and nonallergic vasomotor rhinitis (VMR). SCOPE: Searches of journal articles including the title word 'azelastine' from 1979 through the present were conducted by the product manufacturer primarily through Medline and EMBASE but also included, at various times, Dialog, Biosis, Toxline, and Diogenes (an adverse-event database). One limitation of the present review is that it could not exclude the possibility of publication bias, whereby findings from smaller studies and/or trials with negative findings may not have been published. FINDINGS: Azelastine is a phthalazinone derivative with H(1) receptor binding approximately tenfold greater than chlorpheniramine on a milligram-per-milligram basis. Azelastine has demonstrated a wide range of pharmacologic effects on chemical mediators of inflammation including leukotrienes, kinins, and platelet activating factor in vitro and in vivo. The molecule also has been shown to downregulate intercellular adhesion molecule-1 expression and to reduce inflammatory cell migration in patients with rhinitis. Well-controlled studies in SAR and VMR demonstrated that azelastine nasal spray improves nasal symptoms of rhinitis, including congestion and postnasal drip, and has a rapid onset of action that appears likely due to topical activity. Azelastine nasal spray has demonstrated greater efficacy when used in combination with fluticasone propionate nasal spray when compared to either agent alone, and this combination may provide benefit for patients with moderate-to-severe rhinitis. Bitter taste is the most common side effect associated with azelastine nasal spray and this problem can be mitigated by the dosing technique recommended by the manufacturer in the product labeling. The incidence of somnolence also may be reduced with the recommended administration technique. CONCLUSIONS: Azelastine is an effective, rapid-acting, and well-tolerated second-generation antihistamine that improves nasal symptoms associated with SAR and VMR. Clinical studies demonstrated that azelastine nasal spray can improve symptoms of SAR in patients who remained symptomatic after treatment with oral antihistamines and that azelastine nasal spray in combination with fluticasone nasal spray provided significantly (p < 0.05) greater relief than either agent alone in patients with SAR. PMID- 17723161 TI - Special issue on "molecular targets, biomarkers and animal models for anti-cancer pharmacological research: potentials and challenges from chemoprevention to chemotherapeutic treatment". PMID- 17723162 TI - Biomarkers for diet and cancer prevention research: potentials and challenges. AB - As cancer incidence is projected to increase for decades there is a need for effective preventive strategies. Fortunately, evidence continues to mount that altering dietary habits is an effective and cost-efficient approach for reducing cancer risk and for modifying the biological behavior of tumors. Predictive, validated and sensitive biomarkers, including those that reliably evaluate "intake" or exposure to a specific food or bioactive component, that assess one or more specific biological "effects" that are linked to cancer, and that effectively predict individual "susceptibility" as a function of nutrient nutrient interactions and genetics, are fundamental to evaluating who will benefit most from dietary interventions. These biomarkers must be readily accessible, easily and reliably assayed, and predictive of a key process(es) involved in cancer. The response to a food is determined not only by the effective concentration of the bioactive food component(s) reaching the target tissue, but also by the amount of the target requiring modification. Thus, this threshold response to foods and their components will vary from individual to individual. The key to understanding a personalized response is a greater knowledge of nutrigenomics, proteomics and metabolomics. PMID- 17723163 TI - Predicting the physiological relevance of in vitro cancer preventive activities of phytochemicals. AB - There is growing interest in the ability of phytochemicals to prevent chronic diseases, such as cancer and heart disease. However, some of these agents have poor bioavailability and many of the in-depth studies into their mechanisms of action have been carried out in vitro using doses which are unachievable in humans. In order to optimize the design of chemopreventive treatment, it is important to determine which of the many reported mechanisms of action are clinically relevant. In this review we consider the physiologically achievable doses for a few of the best studied agents (indole-3-carbinol, diindolylmethane, curcumin, epigallocatechin-3-gallate and resveratrol) and summarize the data derived from studies using these low concentrations in cell culture. We then cite examples of in vitro effects which have been observed in vivo. Finally, the ability of agent combinations to act synergistically or antagonistically is considered. We conclude that each of the compounds shows an encouraging range of activities in vitro at concentrations which are likely to be physiologically relevant. There are also many examples of in vivo studies which validate in vitro observations. An important consideration is that combinations of agents can result in significant activity at concentrations where any single agent is inactive. Thus, for each of the compounds reviewed here, in vitro studies have provided useful insights into their mechanisms of action in humans. However, data are lacking on the full range of activities at low doses in vitro and the benefits or otherwise of combinations in vivo. PMID- 17723165 TI - Leukemia, an effective model for chemical biology and target therapy. AB - The rapid rise of chemical biology aimed at studying signaling networks for basic cellular activities using specific, active small molecules as probes has greatly accelerated research on pathological mechanisms and target therapy of diseases. This research is especially important for malignant tumors such as leukemia, a heterogeneous group of hematopoietic malignancies that occurs worldwide. With the use of a chemical approach combined with genetic manipulation, great progress has been achieved over the past few decades on the biological, molecular and cytogenetic aspects of leukemia, and in its diagnosis and therapy. In particular, discoveries of the clinical effectiveness of all-trans retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia and the kinase inhibitors Imatinib and Dasatinib in the treatment of chronic myelogenous leukemia not only make target therapy of leukemia a reality, but also push mechanisms of leukemogenesis and leukemic cell activities forward. This review will outline advances in chemical biology that help our understanding of the molecular mechanisms of cell differentiation and apoptosis induction and target therapy of leukemia. PMID- 17723166 TI - Emerging roles of deubiquitinating enzymes in human cancer. AB - Protein modifications by the covalent linkage of ubiquitin have significant involvement in many cellular processes, including stress response, oncogenesis, viral infection, transcription, protein turnover, organelle biogenesis, DNA repair, cellular differentiation, and cell cycle control. Protein ubiquitination and subsequent degradation by the proteasome require the participation of both ubiquitinating enzymes and deubiquitinating enzymes. Although deubiquitinating enzymes constitute a large family in the ubiquitin system, the study of this class of proteins is still in its infant stage. Recent studies have revealed a variety of molecular and biological functions of deubiquitinating enzymes and their association with human diseases. In this review we will discuss the possible roles that deubiquitinating enzymes may play in cancers. PMID- 17723164 TI - Targeting multiple signal pathways by chemopreventive agents for cancer prevention and therapy. AB - In recent years, growing interest has been focused on the field of cancer prevention. Cancer prevention by chemopreventive agents offers significant promise for reducing the incidence and mortality of cancer. Chemopreventive agents may exert their effects either by blocking or metabolizing carcinogens or by inhibiting tumor cell growth. Another important benefit of chemopreventive agents is their nontoxic nature. Therefore, chemopreventive agents have recently been used for cancer treatment in combination with chemotherapeutics or radiotherapy, uncovering a novel strategy for cancer therapy. This strategy opens a new avenue from cancer prevention to cancer treatment. In vitro and in vivo studies have demonstrated that chemopreventive agents could enhance the antitumor activity of chemotherapeutics, improving the treatment outcome. Growing evidence has shown that chemopreventive agents potentiate the efficacy of chemotherapy and radiotherapy through the regulation of multiple signaling pathways, including Akt, NF-kappaB, c-Myc, cyclooxygenase-2, apoptosis, and others, suggesting a multitargeted nature of chemopreventive agents. However, further in-depth mechanistic studies, in vivo animal experiments, and clinical trials are needed to investigate the effects of chemopreventive agents in combination treatment of cancer with conventional cancer therapies. More potent natural and synthetic chemopreventive agents are also needed to improve the efficacy of mechanism-based and targeted therapeutic strategies against cancer, which are likely to make a significant impact on saving lives. Here, we have briefly reviewed the role of chemopreventive agents in cancer prevention, but most importantly, we have reviewed how they could be useful for cancer therapy in combination with conventional therapies. PMID- 17723167 TI - Keap1 eye on the target: chemoprevention of liver cancer. AB - Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, causing nearly 600,000 deaths each year. Increased risk of HCC due to chronic infection with hepatitis B virus (HBV) and exposure to dietary aflatoxins is responsible for many of these deaths. Prevention strategies targeting HBV infection and aflatoxin exposure could dramatically impact the rates of HCC. Universal HBV vaccination programs have begun in some high-risk areas. Strategies to reduce aflatoxin contamination in food stores have also been implemented. However, complete elimination of aflatoxin contamination might not be possible. For this reason, chemoprevention strategies which alter aflatoxin disposition are a practical strategy to reduce the incidence of HCC in populations with high dietary aflatoxin exposure. The mechanisms of aflatoxin-induced hepatocarcinogenesis are well known. This knowledge provides the basis for evaluation of both exposures to aflatoxin, as well as modulation of aflatoxin disposition by chemopreventive agents. Products of aflatoxin DNA damage and toxicity as well as other metabolites can be used as biomarkers to evaluate modulation of aflatoxin disposition. Modulation of aflatoxin disposition can be achieved through induction of conjugating and cytoprotective enzymes. Many of these enzymes are regulated through Kelch ECH-associating protein 1 (Keap1)-NF-E2 related factor 2(Nrf2)-antioxidant response element (ARE) signaling, making this pathway an important molecular target for chemoprevention. Rodent studies have identified several classes of chemopreventive agents which induce cytoprotective genes. These inducers include phenolic antioxidants, dithiolethiones, isothiocyanates, and triterpenoids. Furthermore, clinical interventions have shown that inducers of Keap1-Nrf2- ARE signaling increase cytoprotective enzyme expression, resulting in modulation of aflatoxin disposition. Much work remains to be done in order to take promising chemopreventive agents from preclinical evaluation to application in at-risk populations. However, appropriately designed clinical trials will aid in this process, which can have profound impact on the incidence of HCC. PMID- 17723168 TI - Discovery and development of sulforaphane as a cancer chemopreventive phytochemical. AB - Sulforaphane (SF) is a phytochemical that displays both anticarcinogenic and anticancer activity. SF modulates many cancer-related events, including susceptibility to carcinogens, cell death, cell cycle, angiogenesis, invasion and metastasis. We review its discovery and development as a cancer chemopreventive agent with the intention of encouraging further research on this important compound and facilitating the identification and development of new phytochemicals for cancer prevention. PMID- 17723169 TI - Molecular targets of cancer chemoprevention by garlic-derived organosulfides. AB - The medicinal benefits of Allium vegetables, especially garlic, have been noted throughout recorded history. The known health benefits of Allium vegetables and their constituents include cardiovascular protective effects, stimulation of immune function, reduction of blood glucose level, radioprotection, improvement of memory loss, protection against microbial, viral and fungal infections, as well as anticancer effects. Population-based case control studies have suggested an inverse correlation between dietary intake of Allium vegetables and the risk of different types of cancers. The anticarcinogenic effect of Allium vegetables including garlic is attributed to organosulfur compounds (OSC), which are highly effective in affording protection against cancer in animal models induced by a variety of chemical carcinogens. More recent studies have shown that certain naturally occurring OSC analogues can suppress proliferation of cancer cells in culture and in vivo. The OSC-induced changes in the proliferation of cancer cells are frequently associated with perturbations in cell cycle progression and induction of G2/M phase arrest. The OSC have also been demonstrated to induce apoptosis via the intrinsic pathway by altering the ratio of the Bcl-2 family of proteins both in cell culture and in in vivo models. Anti-angiogenic activity for garlic-derived OSC has also been documented. This article summarizes current knowledge on molecular targets of cancer chemoprevention by OSC. PMID- 17723170 TI - Oriental herbs as a source of novel anti-androgen and prostate cancer chemopreventive agents. AB - Androgen and androgen receptor (AR) signaling are crucial for the genesis of prostate cancer (PCa), which can often develop into androgen-ligand-independent diseases that are lethal to the patients. Recent studies show that even these hormone-refractory PCa require ligand-independent AR signaling for survival. As current chemotherapy is largely ineffective for PCa and has serious toxic sideeffects, we have initiated a collaborative effort to identify and develop novel, safe and naturally occurring agents that target AR signaling from Oriental medicinal herbs for the chemoprevention and treatment of PCa. We highlight our discovery of decursin from an Oriental formula containing Korean Angelica gigas Nakai (Dang Gui) root as a novel anti-androgen/AR agent. We have identified the following mechanisms to account for the specific anti-AR actions: rapid block of AR nuclear translocation, inhibition of binding of 5alpha-dihydrotestesterone to AR and increased proteasomal degradation of AR protein. Furthermore, decursin lacks the agonist activity of the "pure" anti-androgen bicalutamide and is more potent than bicalutamide in inducing PCa apoptosis. Structure-activity analyses reveal a critical requirement of the side-chain on decursin or its structural isomer decursinol angelate for anti-AR, cell cycle arrest and proapoptotic activities. This work demonstrates the feasibility of using activity-guided fractionation in cell culture assays combined with mechanistic studies to identify novel anti-androgen/ AR agents from complex herbal mixtures. PMID- 17723172 TI - Biomarker and animal models for assessment of retinoid efficacy in cancer chemoprevention. AB - Vitamin A is essential for normal growth and development. Epidemiology and laboratory studies suggest that decreased vitamin A levels and defective metabolism/ action may contribute to the genesis of certain cancers. Based on this information, natural and synthetic derivatives of vitamin A (retinoids) have been used for chemoprevention of cancer. Retinoids have had some success in the chemoprevention of leukoplakia and in the decreased incidence of second primaries in head and neck cancer. There is little information on biomarkers that can be used to assess the efficacy of the chemopreventive activity of retinoids. The ability of retinoids to induce RARb has been consistently shown to correlate with the response of cells and tissues to retinoic acid, but few other biomarkers have been certified as indicators of retinoid activity. In light of the failure of the ATBC and CARET clinical intervention trials for chemoprevention of lung cancer, greater use of animal models for chemoprevention studies is necessary. The potential combination of phytochemicals that inhibit DNA methyltransferase activity with retinoids holds promise for more effective chemoprevention of retinoid-unresponsive premalignant lesions. PMID- 17723171 TI - Vitamin D and prevention of breast cancer. AB - Epidemiologic data have demonstrated that breast cancer incidence is inversely correlated with indices of vitamin D status, including ultraviolet exposure, which enhances epidermal vitamin D synthesis. The vitamin D receptor (VDR) is expressed in mammary epithelial cells, suggesting that vitamin D may directly influence sensitivity of the gland to transformation. Consistent with this concept, in vitro studies have demonstrated that the VDR ligand, 1,25 dihydroxyvitamin D (1, 25D), exerts negative growth regulatory effects on mammary epithelial cells that contribute to maintenance of the differentiated phenotype. Furthermore, deletion of the VDR gene in mice alters the balance between proliferation and apoptosis in the mammary gland, which ultimately enhances its susceptibility to carcinogenesis. In addition, dietary supplementation with vitamin D, or chronic treatment with synthetic VDR agonists, reduces the incidence of carcinogen-induced mammary tumors in rodents. Collectively, these observations have reinforced the need to further define the human requirement for vitamin D and the molecular actions of the VDR in relation to prevention of breast cancer. PMID- 17723173 TI - Tea beverage in chemoprevention and chemotherapy of prostate cancer. AB - Prostate cancer (PCa) is the most frequently diagnosed malignancy and the second leading cause of cancer-related deaths in American males with similar trends in many western countries. The existing treatment approaches and surgical intervention have not been able to effectively cope with this dreaded disease. For these reasons, it is necessary to intensify our efforts for a better understanding of the disease process and for the development of novel approaches for its prevention and treatment. Based on considerable evidence from in vivo and in vitro data and epidemiological studies, in recent years the beverage tea has gained considerable attention for reducing the risk of several cancers. Much of the cancer preventive effects of tea, especially green tea appear to be mediated by the polyphenols present therein. Geographical evidence suggests that the incidence and occurrence of PCa is lower in populations that consume tea regularly. This evidence suggests that tea polyphenols could be extrapolated to optimize their chemopreventive properties against PCa. PCa represents an excellent candidate disease for chemoprevention because it is typically diagnosed in men over 50 years of age and therefore, even a modest delay in neoplastic development achieved through pharmacological or nutritional intervention could result in a substantial reduction in the incidence of clinically detectable disease. In this review we address the issue of possible use of tea, especially green tea, for the prevention as well as treatment of PCa. PMID- 17723175 TI - Prevention and therapy of squamous cell carcinoma of the rodent esophagus using freeze-dried black raspberries. AB - AIM: This study was conducted to determine if short-term treatment of Nnitrosomethylbenzylamine (NMBA)-induced tumors in the rat esophagus with dietary freeze-dried black raspberries (FBR) would result in tumor regression and enhanced survival of the animals. METHODS: Four-week-old male Fisher-344 rats were administered an AIN-76A control diet and injected subcutaneously with 0.5 mg/kg NMBA once per week for 15 weeks. At 19 weeks, when rats had an average of 5 6 tumors (papillomas) per esophagus, they were given a control diet containing either 5%, 10%, or 20% FBR. After 7 weeks of berry treatment, all surviving rats were killed and tumor incidence, number and volume were determined. RESULTS: Esophageal tumor incidences, numbers and volumes in NMBA-treated rats were not influenced by any of the berry treatments. There were progressive increases in the survival of NMBA-treated rats fed 5%-20% FBR diets; however, these increases were not significant. CONCLUSION: FBR at 5%, 10%, and 20% of the diet had no effect on the development of NMBA-induced tumors in the rat esophagus or on animal survival when administered for 7 weeks beginning at the papilloma stage of tumor development. Thus, FBR appear to have no therapeutic value in the treatment of esophageal tumors. In contrast, dietary FBR are highly effective in preventing the development of NMBA-induced esophageal tumors in rats when administered before and during NMBA treatment or shortly after NMBA treatment when the esophagi contain preneoplastic (dysplastic) lesions of varying degrees of severity. PMID- 17723174 TI - Cancer chemoprevention by phytochemicals: potential molecular targets, biomarkers and animal models. AB - Recent studies have strongly indicated that certain daily-consumed dietary phytochemicals could have cancer protective effects against transgenic mice cancer models and cancers mediated by carcinogens, irradiations and carcinogenic metabolites derived from exogenous or endogenous sources. The cancer-protective effects elicited by these dietary compounds are believed to be due at least in part to the induction of cellular defense systems including the detoxifying and antioxidant enzymes system, as well as the inhibition of anti-inflammatory and anti-cell growth signaling pathways culminating in cell cycle arrest and/or celldeath. In this review, we summarize the potential mechanisms including the modulation of nuclear factor kappaB (NF-kappaB), cyclooxygenases-2 (COX-2), activator protein-1 (AP-1), mitogen-activated protein kinases (MAPKs) and the induction of phase II cellular detoxifying and antioxidant enzymes mediated mainly by the antioxidant response elements (ARE) within the promoter regions of these genes through nuclear factor-erythroid 2-related factor 2 (Nrf2), a member of the Cap "n" collar (CNC) family of the basic region-leucine zipper transcription factor. In addition, we also review several animal models of carcinogenesis and cancer chemopreventive efficacy studies of these animal models using dietary chemopreventive compounds. Finally, we discuss the cellular signaling cascades mediated by Nrf2, NF-kappaB, AP-1, MAPKs and COX-2, which have been considered to play pivotal roles in tumor initiation, promotion and progression processes, and could be promising molecular targets for the design of drugs targeting cancer prevention and therapy. PMID- 17723176 TI - Development of novel agents based on nitric oxide for the control of colon cancer. AB - Nitric oxide-donating nonsteroidal anti-inflammatory drugs (NO-NSAIDs) represent a novel class of compounds that hold promise as agents for the control of colon cancer. They are derivatives of conventional NSAIDs that have been modified by adding to them, via a spacer molecule, a nitric oxide releasing moiety. The expectation is that the combined effects of NO and the NSAID moiety will exceed those of each structural component alone. Extensive work has demonstrated their potency and efficacy in preclinical models of colon cancer. The mechanism of action of NO-NSAIDs involves the modulation of several critical cellular signaling pathways, whereas the induction of a state of oxidative stress, at least by NO-aspirin, appears to be a major proximal event. Clinical trials are needed to assess the role of NO-NSAIDs in the control of colon cancer. PMID- 17723178 TI - Dextran sulfate sodium-induced colitis-associated neoplasia: a promising model for the development of chemopreventive interventions. AB - Individuals diagnosed with ulcerative colitis face a significantly increased risk of developing colorectal dysplasia and cancer during their lifetime. To date, little attention has been given to the development of a chemopreventive intervention for this high-risk population. The mouse model of dextran sulfate sodium (DSS) - induced colitis represents an excellent preclinical system in which to both characterize the molecular events required for tumor formation in the presence of inflammation and assess the ability of select agents to inhibit this process. Cyclic administration of DSS in drinking water results in the establishment of chronic colitis and the development of colorectal dysplasias and cancers with pathological features that resemble those of human colitis associated neoplasia. The incidence and multiplicity of lesions observed varies depending on the mouse strain used (ie, Swiss Webster, C57BL/6J, CBA, ICR) and the dose (0.7%-5.0%) and schedule (1-15 cycles with or without a subsequent recovery period) of DSS. The incidence of neoplasia can be increased and its progression to invasive cancer accelerated significantly by administering DSS in combination with a known colon carcinogen (azoxymethane (AOM), 2-amino-3 methylimidazo[4,5-f]quinoline (IQ), 2-amino-1- methyl-6-phenylimidazo[4,5 b]pyridine (PhIP)) or iron. More recent induction of colitis-associated neoplasia in genetically defined mouse strains has provided new insight into the role of specific genes (ie, adenomatous polyposis coli (Apc), p53, inducible nitric oxide synthase (iNOS), Msh2) in the development of colitis-associated neoplasias. Emerging data from chemopreventive intervention studies document the efficacy of several agents in inhibiting DSS-induced neoplasia and provide great promise that colitis-associated colorectal neoplasia is a preventable disease. PMID- 17723177 TI - From dissection of disease pathogenesis to elucidation of mechanisms of targeted therapies: leukemia research in the genomic era. AB - Leukemia is a group of heterozygous diseases of hematopoietic stem/progenitor cells that involves dynamic change in the genome. Dissection of genetic abnormalities critical to leukemia initiation provides insights into the elusive leukemogenesis, identifies distinct subsets of leukemia and predicts prognosis individually, and can also provide rational therapeutic targets for curative approaches. The past three decades have seen tremendous advances in the analysis of genotype-phenotype connection of leukemia, and in the identification of molecular biomarkers for leukemia subtypes. Intriguingly, differentiation therapy, targeted therapy and chemotherapy have turned several subtypes of leukemia from highly fatal to highly curable. The use of all-trans retinoic acid and arsenic trioxide, which trigger degradation of PML-RARalpha, the causative fusion protein generated by t (15;17) translocation in acute promyelocytic leukemia (APL), has led to a dramatic improvement of APL clinical outcome. Imatinib mesylate/ Gleevec/STI571, which inhibits the tyrosine kinase activity of BCR-ABL oncoprotein, has now become the new gold standard for the treatment of chronic myeloid leukemia. Optimal use of chemotherapeutic agents together with a stringent application of prognostic factors for risk-directed therapy in clinical trials has resulted in a steady improvement in the treatment outcome of acute lymphoblastic leukemia. Hence, the pace of progress extrapolates to a prediction of leukemia control in the twenty-first century. PMID- 17723179 TI - Salvicine, a novel topoisomerase II inhibitor, exerts its potent anticancer activity by ROS generation. AB - Salvicine is a novel diterpenoid quinone compound obtained by structural modification of a natural product lead isolated from a Chinese herb with potent growth inhibitory activity against a wide spectrum of human tumor cells in vitro and in mice bearing human tumor xenografts. Salvicine has also been found to have a profound cytotoxic effect on multidrug-resisitant (MDR) cells. Moreover, Salvicine significantly reduced the lung metastatic foci of MDA-MB-435 orthotopic xenograft. Recent studies demonstrated that salvicine is a novel non intercalative topoisomerase II (Topo II) poison by binding to the ATPase domain, promoting DNA-Topo II binding and inhibiting Topo II-mediated DNA relegation and ATP hydrolysis. Further studies have indicated that salcivine-elicited ROS plays a central role in salvicine-induced cellular response including Topo II inhibition, DNA damage, circumventing MDR and tumor cell adhesion inhibition. PMID- 17723180 TI - Combinatorial strategies for cancer eradication by silibinin and cytotoxic agents: efficacy and mechanisms. AB - In an effort to develop effective alternative strategies that increase the therapeutic efficacy and minimize the systemic toxicity of chemotherapeutic agents, more efforts are being directed towards the investigation of dietary supplements and other phytotherapeutic agents for their synergistic efficacy in combination with anticancer drugs. One such agent is silibinin, which has shown promising chemopreventive and anticancer effects in various in vitro and in vivo studies. The present review summarizes the effects of the combination of silibinin and chemotherapeutic drugs on the growth inhibition, cell cycle regulation, and apoptosis induction in prostate, breast, and lung cancer systems. Together, the results indicate a synergistic effect of silibinin on growth inhibition, reversal of chemoresistance, apoptosis induction, and a strong increase in G2-M checkpoint arrest when given in combination with these drugs. These results are highly significant with respect to the combined chemotherapy approach, wherein the criteria for combination is that the response has to be synergistic and that the drugs should not share common mechanisms of resistance and not overlap in their major side-effects. PMID- 17723181 TI - Targeted cancer therapies based on antibodies directed against epidermal growth factor receptor: status and perspectives. AB - Compelling experimental and clinical evidence suggests that epidermal growth factor receptor (EGFR) plays an important role in the pathogenesis of a variety of human cancers; thus, providing a strong rationale for the development of receptor antagonists as effective and specific therapeutic strategies for the treatment of EGFR-expressing cancers. Monoclonal antibodies (mAb), owing to their high specificity towards a given target, represent a unique class of novel cancer therapeutics. A number of anti-EGFR mAb are currently being developed in our clinic, including two that have been approved by the United States Food and Drug Administration for the treatment of refractory metastatic colorectal cancer (mCRC) and squamous cell carcinomas of the head and neck (SCCHN). Cetuximab (Erbitux, IMC-C225), an IgG1 mAb, has demonstrated significant antitumor activity, both as a single agent and in combination with chemotherapeutics and radiation, in patients with refractory mCRC and SCCHN, respectively. Panitumumab (Vectibix), an IgG2 mAb, has been approved as a single agent for the treatment of patients with refractory mCRC. These mAb, via blocking ligand/receptor interactions, exert their biological activity via multiple mechanisms, including inhibition of cell cycle progression, potentiation of cell apoptosis, inhibition of DNA repair, inhibition of angiogenesis, tumor cell invasion and metastasis and, potentially, induction of immunological effector mechanisms. Anti-EGFR antibodies have demonstrated good safety profiles and potent anticancer activity in our clinic and may prove to be efficacious agents in the treatment of a variety of human malignancies. PMID- 17723182 TI - From cell signaling to cancer therapy. AB - Cancer has been seriously threatening the health and life of humans for a long period. Despite the intensive effort put into revealing the underlying mechanisms of cancer, the detailled machinery of carcinogenesis is still far from fully understood. Numerous studies have illustrated that cell signaling is extensively involved in tumor initiation, promotion and progression. Therefore, targeting the key molecules in the oncogenic signaling pathway might be one of the most promising ways to conquer cancer. Some targeted drugs, such as imatinib mesylate (Gleevec), herceptin, gefitinib (Iressa), sorafenib (Nexavar) and sunitinib (Sutent), which evolve from monotarget drug into multitarget ones, have been developed with encouraging effects. PMID- 17723184 TI - [Study and evaluation of occupational carcinogens]. PMID- 17723183 TI - Roles of secreted frizzled-related proteins in cancer. AB - The Wnt signaling pathway is implicated in a variety of biological processes ranging from developmental cell fate to human disease. The components involved in Wnt signaling have been under intense investigation over the last 2 decades. Aberrant canonical Wnt activation has been linked to tumor formation and involves activation of effector molecules or loss of tumor suppressor function. Secreted frizzled-related proteins (sFRPs) are Wnt antagonists. In recent years, accumulating evidence has suggested that sFRPs act as tumor suppressors because their expression is frequently silenced in cancer by promoter hypermethylation. However, sFRPs may also promote cell growth in some contexts. Here, we focus on the known knowledge of sFRPs in tumorigenesis. PMID- 17723185 TI - [Nested case-control study of chrysotile and lung cancer]. AB - OBJECTIVE: To investigate the relationship between simple exposure to chrysotile and lung cancer. METHODS: The nested case-control study method was used. All of lung cancer cases collected from a male fixed prospective cohort with follow-up of 30 years served as cases and a 1:4 matched proportion was used to select non cancer case as controls. Controls matched for sex age (+/-5 years old), work time (+/-5 years) and smoking were collected in the same cohort. RESULTS: Forty cases died of lung cancer in the study cohort, and the incidence was higher than the average incidence (SMR =1.77). The top four work types of death density were raw material (741.5), combing and spinning (424.3), weaving (365.0), and repairing (285.5), which was consistent with exposed level. According to the exposed level of chrysotile, the research objects were divided into the high level group and the low level group. The result demonstrated that lung cancer incidence of the high exposed level group of chrysotile was higher (OR = 3.7 95% CI 2.30 approximately 8.16), compared with the low exposed level group. CONCLUSION: Simple exposure to chrysotile can increase the risk of lung cancer for workers who are exposed to chrysotile. PMID- 17723186 TI - [Burden of major cancers on years of life lost with premature death in crocidolite-contaminated area in Dayao]. AB - OBJECTIVE: To evaluate the effects of environmental low-dose exposure to crocidolite on people's health and the society. METHODS The mortality data of cancer between 1994 and 2003 in an environmental crocidolite-contaminated area was obtained from hospital medical records of Dayao Center for Disease Prevention and Control, and Dayao Public Health Bureau. The years of life lost with premature death (YLLs), was used to measure and assess the death, health losses and social burden of cancer in this area. RESULTS: In the environmental crocidolite-contaminated area, lung cancer was the prime cause of death in all kinds of cancers between 1994 and 2003, followed by liver cancer, mesothelioma stomach cancer and colorectal cancer, with mortality 10.15/10(5), 9.04/10(5), 8.48/10(5), 3.96/10(5) and 3.55/10(5) respectively. The mortality of main cancer in male and female increased with age growing except that of breast cancer in female. Results showed that the types of leading cancers of YLLs were liver cancer, lung cancer, mesothelioma, leukemia and stomach cancer with YLLs 1981.39 person-year, 1886.63 person-year, 1799.23 person-year, 948.01 person-year and 754.18 person-year respectively. The distribution of YLLs was similar in both sexes, higher in the middle age group (aged from 15 to 44 years and 45 to 59 years) and lower in other age groups. The indirect economic loss resulting from lung cancer (15.02% of the total loss), liver cancer (13.98% of the total loss) and mesothelioma (13.01% of the total loss) was relatively great. The YLLs and the indirect economic loss attributable to environmental low-dose exposure to crocidolite were 3092.23 person-year and 5,175,800 Yuan respectively. CONCLUSION: Lung cancer, liver cancer, mesothelioma, leukemia and breast cancer are the major cancers with an important impact on people's health and premature mortality in the environmental crocidolite-contaminated area. The impact of cancer mortality is more severer in those aged over 45 years. Social burden of cancer is the greatest in persons aged from 15 to 59 years. Policies and plans should be worked out for the protection of environment and the prevention of cancer. PMID- 17723187 TI - [Treatment 16 cases of acute paraquat poisoning]. PMID- 17723188 TI - [Pathological study of lung cancer induced by Yunnan tin mine dusts in F344 rats]. AB - OBJECTIVE: To set up animal models of the lung cancer induced by Yunnan tin mineral dusts (no radon) in F344 rats and to explore the process of carcinogenesis and pathologic alterations in various stages of malignant transformation in the animal models. METHODS: One hundred and ninety F344 rats were randomly divided into Yunnan tin mineral dust group (100 rats), furfural physiological saline group (30 rats), physiological saline group (30 rats) and normal control group (30 rats). The intratracheal instillation with mass fraction of 6% suspension liquid mixture Yunnan tin mineral dusts, volume fraction of 2% furfural physiological saline and physiological saline 0.2 ml was performed in the rates once per week respectively except normal control group. Then the rats were sacrificed in batch periodically after one week. The last rat was exposed to the tin mine dusts for 100 weeks. The morphological process and tumor formation were dynamically observed under LM and TEM. Immunohistochemistry detection of cytokeratin of High MW and low MW was used for tumor classification. Pollak stein was used to evaluate the development of fibrosis of lung in the rats. RESULTS: Bronchoalveolar inflammation occurred in the early stage after the intratracheal instillation of Yunnan tin mineral dust was performed in F344 rates. Along with reduction of inflammation, collagen fibrils increased at alveolar interstices. Simple hyperplasia, papillary hyperplasia and metaplasia of the epithelial cells in alveolar and bronchi were observed, followed by atypical adenomatous hyperplasia and squamous dysplasia. Lung cancer was induced in the end. Among the 14 cases of lung cancer, 9 cases were adenocarcinoma, 2 squamous cell carcinoma and 3 mixed carcinoma. No lung cancer occurred in other three control groups. There was a significant difference in the malignancy rate between the experimental group and the three control groups (P < 0.01). The squamous metaplasia and squamous carcinoma were found in alveoli that expressed cytokeratin of High MW. Lung fibrosis was found in 31 cases of in the tin mineral dust group. The greater the mineral dust deposit was, the more serious the alveolar fibrosis was. CONCLUSION: Yunnan tin mineral dusts without radon induce lung cancer in rates. The adenocarcinoma and squamous carcinomas induced in F344 rat lung can occur in the alveoli. The further study on whether type II alveolar epithelial cells are the origin cells of adenocarcinoma and some peripheral squamous lung carcinomas is worthwhile. PMID- 17723189 TI - [Effect of Chinese herbal drugs and tetrandrine on TGF-beta1 signaling pathway]. AB - OBJECTIVE: To investigate the molecule mechanism of the anti-fibrotic effects of Chinese herbal drugs (Qidan granules) in rats. METHODS: The male rats were randomly divided into four experimental groups: normal group, model group, Qidan group, tetrandrine group. Every group had 10 rats. Normal group were treated with physiologic saline while others were treated with silicon dioxide (50 mg/rat) by intratracheal instillation to induce silicosis. On 30th day Qidan group and Tetrandrine group were treated with Qidan granules (3125 mg/kg) or treated with tetrandrine (22 mg/kg) respectively. All the rats were scarified after 5 months. Lung/body coefficient was measured. Content of hydroxyproline was measured by alkaline hydrolysis. The gene expression of transforming growth factor-beta1 in bronchoalveolar lavage fluid was examined by using enzyme-linked immunosorbent assay (ELISA). The gene expressions of transforming growth factor-beta1, transcription factor Smad 3 and Smad 7 in lung were analyzed by using immunohistochemical technique (SP) and the image analysis. RESULTS: Model group mainly had Grade III approximately IV silicotic nodule while Qidan group and tetrandrine group had Grade II silicotic nodule. In Qidan group and tetrandrine group, lung/body coefficient and content of hydroxyproline and expression of transforming growth factor-beta1 and Smad3 in lung and expression of transforming growth factor-beta1 in bronchoalveolar lavage fluid were lower than those in model group (P < 0.05). Expression of Smad 7 in lung was higher than model group (P < 0.05). Injury of kidney occurred in tetrandrine group. CONCLUSION: Qidan granules and tetrandrine could inhibit expression of both Smad 7 and transforming growth factor-beta1 and promote expression of Smad 3. Qidan granules and tetrandrine could inhibit remarkably silicotic fibrosis in rats. Qidan granules are safer than tetrandrine. PMID- 17723190 TI - [Histomorphological feature of silicotic nodules under Warthin-Starry silver staining and its possible prompt value in the histopathologic examination]. AB - OBJECTIVE: To investigate histomorphological feature of silicotic nodules under Warthin-Starry (WS) silver staining and its value in the histopathological examination. METHODS: Six cases with silicosis obtained by autopsy and 21 cases with sarcoidosis were collected (among which 3 cases were obtained by autopsy and 18 cases were obtained by biopsy). The serial sections of those paraffin embedded samples were applied respectively for (1) hematoxylin and eosin (HE) staining, (2) WS staining, (3) streptomyces avidin-peroxidase (SP) immunohistochemical staining for mouse anti-human CD68 monoclonal antibody, (4) observing under transmission electron microscope (TEM), (5) X-ray spectrum chemical element analysis(X-RSA). The emphasis of observation and analysis were the dust particles in silicotic nodules and granulomas cells (dust cells, epithelioid cells and multinucleated giant cells in the granulomas). The dust particles deposit in the granulomas were graded under the HE and WS staining. RESULTS: Under the HE staining the dust particles deposit degrees were (+++) in cellular silicotic nodules, (+) in the fibrous ones, and (-) in the sarcoid nodules; under the WS staining and the dust particles deposit degrees were (+++) in both silicotic nodules whose dust particles were characteristically black, and (+/++) in sarcoid nodules. The dust particles deposit degrees in silicotic nodules were markedly higher than those in sarcoidosis (P < 0.01). The results of immunohistochemical staining indicated that the expression of CD68 in both cells of silicotic nodules and sarcoid nodules were positive. The positive degrees decreased successively with the content of the dust particles. The dust particles of silicotic nodules could be more readily observed than those of sarcoidosis in size and electronic density under TEM. The results of X-RSA indicated that the main chemical element in both dust particles was silicon. CONCLUSION: WS staining is better than HE staining in showing the dust particles of silicotic nodules, which appear characteristically black, especially in the fibrous ones. Together the TEM observation and X-RSA, the silicotic nodules may be prompted. PMID- 17723191 TI - [Automobile tyre colloidal particle induced allergic damage of respiratory system in traffic policemen and its allergenicity]. AB - OBJECTIVE: To explore the damage of respiratory system in the traffic policemen induced by automobile tyre colloidal particle and its allergenicity. METHODS: The respiratory system symptoms in 445 traffic policemen working outside their offices and 243 controls were investigated and their pulmonary ventilation function index such as FVC, FEV(1.0), MMF and V(50) were determined. The specific IgE antibody of automobile tyre colloidal particle of their serum was determined and the skin-prick test of automobile tyre colloidal particle antigen was performed. Sixty-six traffic policemen working outside their offices and 5 controls with the positive of IgE antibody among them were detected by nasal mucosa provocation test. Sixty-six traffic policemen working outside their offices with the positive of IgE antibody were determined by Terbutaline inhalation test. RESULTS: The positive rate of respiratory system symptoms of traffic policemen such as cough, stethocatharsis, short breath, nasal obstruction, sneeze and nose running was 38.02%, 27.03%, 20.00%, 23.08%, 27.47%, 32.09% and 34.95% respectively and significantly higher than those of the control with significant difference (P < 0.01) or (P < 0.05). The positive rate of specific IgE antibody of automobile tyre colloidal particle, skin- prick test and nasal mucosa provocation test was 14.51%, 23.73% and 54.55% respectively with significant difference (P < 0.01) and (P < 0.05). The percentage, the actual figure compared with the prediction figure, of the index of pulmonary ventilation function (FVC, FEV(1.0) MMF and V(50)) of traffic policemen were significantly lower than those of the control. Terbutaline inhalation test in 66 positive subjects of specific IgE antibody of automobile tyre colloidal particle was positive in 44 subjects, accounting for 9.67% in all policemen investigated. CONCLUSION: The automobile tyre colloidal particle is one of etiological factors that induce pulmonary ventilation function damage and could result in allergic asthma of traffic police. PMID- 17723192 TI - [Diagnostic value and clinical application of CT/HRCT for coal workers' pneumoconiosis with large opacities]. AB - OBJECTIVE: To study the diagnostic value of CT/HRCT for the coal workers' pneumoconiosis (CWP) with large opacities. METHODS: Sixty-two patients with CWP were examined with both chest radiograph and CT/HRCT scan. Comparison was done. RESULTS: Large opacities were found in 19 patients in the chest radiograph of 62 patients with CWP. The detection rate was 30.6%. Thirty large opacities were found using chest radiograph. Forty-three patients with large opacities were found using the CT/HRCT. The detection rate was 69.4%. One hundred and twenty three large opacities were found using CT/HRCT. Ninety-three more large opacities were found by CT/HRCT than by chest radiograph. The total detection rate of large opacities by CT was 4.1 times than by chest radiograph. Both differences were statistically significant (chi2 = 18.58, P < 0.01). CT/HRCT found all patients with large opacities detected in the chest radiograph. Seventeen patients with Stage III large opacities (>or= 1.0 cm x 2.0 cm) were found by the chest radiograph. The detection rate was 27.4% (17/62). Twenty-seven large opacities were found using chest radiograph. Thirty-four patients with Stage III large opacities were found using the CT/HRCT. The detection rate was 54.8%. The found Stage III large opacities added up to 67. The found Stage III large opacities by CT/HRCT were 40 more than using chest radiograph. Both differences were statistically significant (chi2 = 9.63, P < 0.01). CT/HRCT was reliable to show the morphology, the inside structure, the tiny lesion and the special location of the large opacities of CWP. It could provide more important information for differential diagnosis. CONCLUSION: CT/HRCT is significantly better than the chest radiograph in the diagnosis of complicated CWP. It can find the large opacities that the chest radiograph can not. It has a great diagnostic and practical value as an assistant examination method. CT/HRCT could be considered as the reference and evidence for staging progression in diagnosis of pneumoconiosis. PMID- 17723194 TI - [COX's proportional hazards model analysis for life span of patients with coal workers' pneumoconiosis]. PMID- 17723193 TI - [HRCT and pathology for nodules in cadaveric lung with coal workers' pneumoconiosis]. AB - OBJECTIVE: To evaluate imaging of high-resolution computed tomography (HRCT) for nodules of cadaveric lungs of coal workers' or coal workers with coal workers' pneumoconiosis (CWP) and to determine types of small nodules of CWP and dust speckle based on CT-pathologic correlation. METHODS: Thirty-two entire lung specimens were available from autopsy of the patients with CWP and coal workers occupationally exposed to coal dusts. They comprised 25 workers without CWP, 3 patients with 0+ stage and 4 patients with I stage. Thirty-two lung specimens were inflated and fixed by Heitzman's method, and underwent coronal single slice computed tomography (SSCT)/multi-slice computed tomography (MSCT) and HRCT scans. Gross specimens section (50 approximately 100 microm of slice thickness) and histological section (5 approximately 8 microm of slice thickness) were performed on seventeen pieces of 10 mm-thickness slices of lung specimen in thirteen cases. The nodules were divided into round, ill defined and stellate-shaped, and their distributions and relationships with pulmonary lobule were analyzed. RESULTS: The findings were as follows (1) 14 cases without CWP and 18 cases with CWP (including 5 cases with I stage 11 cases with II stage and 2 cases with III stage) were diagnosed by pathology. (2) Nodules were displayed on HRCT in 32 cases, among which 29 cases were verified by pathology. There was no significant difference between HRCT and pathology (chi2 = 0.5, 0.25 < P < 0.5). (3) Nodules of CWP on HRCT included well-defined round nodules, ill defined nodules and stellate-shape nodules. Twelve of fourteen round nodules on HRCT were pathologically typical ones. Twenty-six ill defined nodules on HRCT included 14 atypical ones, 11 dust macules and 1 typical one by pathology. Six dust macules and 3 atypical nodules were found by pathology in nine stellate-shape nodules on HRCT. (4) HRCT accurately displayed nodular distributions including nodules adjacent to small artery, thickened septa and subpleural regions. CONCLUSION: HRCT could display typical, atypical nodules and some dust macules presenting pathologic changes, as well as relationship between nodules and structure of pulmonary lobule. PMID- 17723195 TI - [Pathogenic feature and drug resistance analysis for nosocomial infection of patients with pneumoconiosis]. PMID- 17723196 TI - [Analysis of pulmonary ventilation function of 646 patients with coal workers' pneumoconiosis]. PMID- 17723197 TI - [Analysis of pulmonary ventilation function of patients with pneumoconiosis]. PMID- 17723198 TI - [Change of blood fluoride ion concentration in rabbits and rats inhaling perfluoroisobutylene]. PMID- 17723199 TI - [Drug resistance of tuberculosis mycobacteria L forms and related gene mutation of tuberculosis patients with pneumoconiosis in Huainan mine area]. PMID- 17723200 TI - [Change of liver function and blood glucose in patients with acute paraquat poisoning]. PMID- 17723201 TI - [Model for evaluation of hazards of radon induced lung cancer]. PMID- 17723202 TI - [Pneumoconiosis-like lesions in three workers of education institution]. PMID- 17723203 TI - [Autopsy for one death case due to diagnosis error of silicosis complicated with pulmonary alveolar proteinosis]. PMID- 17723204 TI - [Acute nitrite poisoning in four patients]. PMID- 17723205 TI - [Hypertensive crisis induced by percutaneous absorption-caused acute organophosphorus pesticides poisoning in one patient]. PMID- 17723206 TI - [Simulation of results of leakage and diffusion of liquid chlorine from tanks]. PMID- 17723207 TI - [Analysis for papers of last decade for research on pneumoconiosis in China]. PMID- 17723208 TI - Revving the engine: signal transduction fuels T cell activation. AB - For initiation of an immune response, resting T cells must reprogram their metabolism. Continuing the "From the Field" series (see Editorial [2007] 26, 131), Jones and Thompson draw attention to the importance of metabolism during T cell activation and consider how this process is regulated by receptor-mediated signal transduction. PMID- 17723209 TI - The alphabeta T cell repertoire comes into focus. AB - The size of the lymphocyte repertoire is of great interest, but direct information has been elusive. Moon et al. (2007) report the enumeration and isolation of naive CD4(+) T cells and show their numbers could predict the size and diversity of the primary immune response. PMID- 17723210 TI - CD8(+) T cell differentiation: choosing a path through T-bet. AB - Activated CD8(+) T cells can differentiate into transient effector cells or long lived memory cells. In this issue of Immunity, Joshi et al. (2007) suggest that inflammatory cytokines dictate this balance by regulating the expression of the transcription factor T-bet. PMID- 17723211 TI - Islet beta-cell death - fuel to sustain autoimmunity? AB - Under what context do dying beta-cells enhance the autoimmune process in type 1 diabetes? Kim et al. (2007) find that secondary necrosis of beta-cells can prime the autoimmune response via uptake by and activation of antigen-presenting cells through Toll-like receptor 2. PMID- 17723212 TI - The expanding universe of regulatory T cell subsets in cancer. AB - Evidence has indicated that failed antitumor immunity is dominated by immunosuppressive mechanisms within the tumor microenvironment. In this issue of Immunity, Peng et al. (2007) add to this list by describing tumor-infiltrating gammadelta T cells that have regulatory function. PMID- 17723213 TI - Balancing mucosal immunity: caught between CYLD and Charybdis. AB - The molecular mechanism of acute lung injury caused by Streptococcus pneumoniae is unclear. In this issue of Immunity, Lim et al. (2007) demonstrate that CYLD, a deubiquinating enzyme, represses the expression of plasminogen activator inhibitor-1, which is critical in preventing tissue damage. PMID- 17723215 TI - p110gamma and p110delta phosphoinositide 3-kinase signaling pathways synergize to control development and functions of murine NK cells. AB - Phosphoinositide 3-kinases (PI-3Ks) are key enzymes for cell development, activation, and survival. Here we showed that PI-3K class IB and class IA catalytic subunits, p110gamma and p110delta, played a crucial role in the development and functions of murine NK cells. p110gamma deficiency and impairment of G protein-coupled receptor (GPRC) signaling prevented full NK cell maturation. Concomitant loss of p110gamma and p110delta exacerbated this defect, resulting in a very small population of NK cells with a highly immature phenotype in the bone marrow and periphery. Moreover, combined p110gamma and p110delta signals were required for cytotoxicity and activation of the kinase ERK during NK cell-target cell interaction. p110gamma played a major role in receptor-induced interferon gamma (IFN-gamma) production through a pathway that involved the kinase ERK and 5 Lipoxigenase, which most likely generates lipid mediators activating GPRCs. Conversely, PI3Ks negatively regulated interleukin-12 (IL-12) and IL-18-induced IFN-gamma by modulating p38 kinase activation. Our data shed light on the multiple intersecting pathways through which PI3Ks control NK cell-mediated innate responses. PMID- 17723216 TI - Alveolar macrophages are the primary interferon-alpha producer in pulmonary infection with RNA viruses. AB - Type I interferons (IFNs) are critical for antiviral responses. Here we generated a knockin mouse in which green fluorescence protein (GFP) was expressed under the control of the Ifna6 promoter. Virus-induced expression of GFP recapitulated various IFN-alpha subtypes. Systemic infection of the mice with Newcastle disease virus (NDV) increased GFP(+) plasmacytoid dendritic cells (pDCs) via the Toll like receptor system, and GFP(+) conventional dendritic cells (cDCs) and macrophages via the RIG-I-like helicase system. By contrast, lung infection with NDV led to IFN-alpha production in alveolar macrophages (AMs) and cDCs, but not in pDCs. Specific depletion of AMs caused a marked defect in the initial viral elimination in the lung. pDCs produced IFN-alpha in the absence of AM-mediated viral recognition, suggesting that pDCs function when the first defense line is broken. Thus, AMs act as a type I IFN producer that is important for the initial responses to viral infection in the lung. PMID- 17723214 TI - Germinal-center organization and cellular dynamics. AB - Germinal centers (GCs) are important sites of antibody affinity maturation. In the classical model, the GC dark zone contains large centroblasts that are rapidly proliferating and undergoing somatic hypermutation of their antibody variable-region genes. Centroblasts give rise to smaller nonproliferating centrocytes in the light zone that compete for binding antigen on follicular dendritic cells. Recently, the approach of real-time imaging of GCs by two-photon microscopy of intact lymph nodes has provided new insights into GC dynamics that both support and challenge fundamental aspects of this model. Here we review recent and older findings on cell migration, proliferation, and interaction dynamics in the GC and discuss a model in which dark- and light-zone cells are morphologically similar, proliferation occurs in both zones, and GC B cells compete for T cell help as well as antigen. PMID- 17723217 TI - Tumor necrosis factor receptor-associated factor 3 is a critical regulator of B cell homeostasis in secondary lymphoid organs. AB - Tumor necrosis factor receptor-associated factor 3 (TRAF3) is an adaptor protein that directly binds to a number of receptors of the tumor necrosis factor receptor (TNF-R) superfamily. Despite in vitro evidence that TRAF3 plays diverse roles in different cell types, little is known about the in vivo functions of TRAF3. To address this gap in knowledge and to circumvent the early lethal effect of TRAF3 null mutations, we generated conditional TRAF3-deficient mice. B-cell specific Traf3(-/-) mice displayed severe peripheral B cell hyperplasia, which culminated in hyperimmunoglobulinemia and increased T-independent antibody responses, splenomegaly and lymphadenopathy. Resting splenic B cells from these mice exhibited remarkably prolonged survival ex vivo independent of B cell activating factor and showed increased amounts of active nuclear factor-kappaB2 but decreased amounts of nuclear protein kinase Cdelta. Furthermore, these mice developed autoimmune manifestations as they aged. These findings indicate that TRAF3 is a critical regulator of peripheral B cell homeostasis and may be implicated in the regulation of peripheral self-tolerance induction. PMID- 17723220 TI - Transfer of movement sequences: bigger is better. AB - Experiment 1 was conducted to determine if proportional transfer from "small to large" scale movements is as effective as transferring from "large to small." We hypothesize that the learning of larger scale movement will require the participant to learn to manage the generation, storage, and dissipation of forces better than when practicing smaller scale movements. Thus, we predict an advantage for transfer of larger scale movements to smaller scale movements relative to transfer from smaller to larger scale movements. Experiment 2 was conducted to determine if adding a load to a smaller scale movement would enhance later transfer to a larger scale movement sequence. It was hypothesized that the added load would require the participants to consider the dynamics of the movement to a greater extent than without the load. The results replicated earlier findings of effective transfer from large to small movements, but consistent with our hypothesis, transfer was less effective from small to large (Experiment 1). However, when a load was added during acquisition transfer from small to large was enhanced even though the load was removed during the transfer test. These results are consistent with the notion that the transfer asymmetry noted in Experiment 1 was due to factors related to movement dynamics that were enhanced during practice of the larger scale movement sequence, but not during the practice of the smaller scale movement sequence. The findings that the movement structure is unaffected by transfer direction but the movement dynamics are influenced by transfer direction is consistent with hierarchal models of sequence production. PMID- 17723218 TI - Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor. AB - As acute infections resolve, effector CD8(+) T cells differentiate into interleukin-7 receptor(lo) (IL-7R(lo)) short-lived effector cells (SLECs) and IL 7R(hi) memory precursor effector cells (MPECs) capable of generating long-lived memory CD8(+) T cells. By using another SLEC marker, KLRG1, we found that KLRG1(hi) effector cells began appearing early during infection and were committed to downregulating IL-7R. Unlike IL-7R(hi) MPECs, KLRG1(hi) IL-7R(lo) SLECs relied on IL-15, but IL-15 could not sustain their long-term maintenance or homeostatic turnover. The decision between SLEC and MPEC fates was regulated by the amount of inflammatory cytokines (i.e., IL-12) present during T cell priming. According to the amount of inflammation, a gradient of T-bet was created in which high T-bet expression induced SLECs and low expression promoted MPECs. These results elucidate a mechanism by which the innate immune system sets the relative amounts of a lineage-determining transcription factor in activated CD8(+) T cells and, correspondingly, regulates their memory cell potential. PMID- 17723221 TI - Extended experience benefits spatial mental model development with route but not survey descriptions. AB - Spatial descriptions symbolically represent environmental information through language and are written in two primary perspectives: survey, analogous to viewing a map, and route, analogous to navigation. Readers of survey or route descriptions form abstracted perspective flexible representations of the described environment, or spatial mental models. The present two experiments investigated the maintenance of perspective in spatial mental models as a function of description perspective and experience (operationalized through repetition), and as reflected in self-paced reading times. Experiment 1 involved studying survey and route descriptions either once or three times, then completing map drawing and true/false statement verification. Results demonstrated that spatial mental models are readily formed with survey descriptions, but require relatively more experience with route descriptions; further, some limited evidence suggests perspective dependence in spatial mental models, even following extended experience. Experiment 2 measured self-paced reading during three successive description presentations. Average reading times over the three presentations reduced more for survey relative to route descriptions, and there was no evidence for perspective specificity in resulting spatial mental models. This supports Experiment 1 findings demonstrating the relatively time-consuming nature of acquiring spatial mental models from route, but not survey descriptions. Results are discussed with regard to developmental, discourse processing, and spatial mental model theory. PMID- 17723222 TI - A simpler analysis for the measurement of second virial coefficients by self interaction chromatography. AB - We describe a thermodynamic approach that supports the adoption of a simplified procedure for the determination of protein second virial coefficients (B(2)) by self-interaction chromatography. Its major advantage over the original method is a decrease in the number of parameters to which magnitudes must be assigned for the determination of B(2). Improved correlation of virial coefficients obtained by the chromatographic procedure with those obtained by light scattering is achieved by taking into account the twofold larger magnitudes of the former because of the experimental distinction between free and immobilized protein molecules in self-interaction chromatography. PMID- 17723219 TI - Tumor suppressor CYLD regulates acute lung injury in lethal Streptococcus pneumoniae infections. AB - Streptococcus pneumoniae (S. pneumoniae) causes high early mortality in pneumococcal pneumonia, which is characterized by acute lung injury (ALI). The molecular mechanisms underlying ALI and the high early mortality remain unknown. Despite recent studies that identify deubiquitinating enzyme cylindromatosis (CYLD) as a key regulator for T cell development, tumor cell proliferation, and NF-kappaB transcription factor signaling, its role in regulating bacteria-induced lethality, however, is unknown. Here, we showed that CYLD deficiency protected mice from S. pneumoniae pneumolysin (PLY)-induced ALI and lethality. CYLD was highly induced by PLY, and it inhibited MKK3-p38 kinase-dependent expression of plasminogen activator inhibitor-1 (PAI-1) in lung, thereby potentiating ALI and mortality. Thus, CYLD is detrimental for host survival, thereby indicating a mechanism underlying the high early mortality of pneumococcal pneumonia. PMID- 17723223 TI - Electrophysical characteristics of Azospirillum brasilense Sp245 during interaction with antibodies to various cell surface epitopes. AB - This work was undertaken to examine the electrooptical characteristics of cells of Azospirillum brasilense Sp245 during their interaction with antibodies developed to various cell surface epitopes. We used the dependences of the cell suspension optical density changes induced by electroorientation on the orienting field frequency (740, 1000, 1450, 2000, and 2800kHz). Cell interactions with homologous strain-specific antibodies to the A. brasilense Sp245 O antigen and with homologous antibodies to whole bacterial cells brought about considerable changes in the electrooptical properties of the bacterial suspension. When genus specific antibodies to the flagellin of the Azospirillum sheathed flagellum and antibodies to the serologically distinct O antigen of A. brasilense Sp7 were included in the A. brasilense Sp245 suspension, the changes caused in the electrooptical signal were slight and had values close to those for the above changes. These findings agree well with the immunochemical characteristics of the Azospirillum O antigens and with the data on the topographical distribution of the Azospirillum major cell surface antigens. The obtained results can serve as a basis for the development of a rapid test for the intraspecies detection of microorganisms. PMID- 17723224 TI - 2,5-Dihydroxybenzoic acid instead of alpha-cyano-4-hydroxycinnamic acid as matrix in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for analyses of in-gel digests of silver-stained proteins. PMID- 17723225 TI - Relationships between anger, symptoms, and cognitive factors in OCD checkers. AB - The purpose of this study was to examine whether individuals diagnosed with obsessive-compulsive disorder (OCD) with primary checking compulsions report higher levels of trait anger and anger expression compared with a student control group, and whether trait anger and anger expression are correlated with specific beliefs and interpretations that are common among individuals who compulsively check. A group of individuals with OCD reporting significant checking compulsions (n=33) and a group of undergraduate students (n=143) completed a questionnaire package that included measures of trait anger and anger expression, as well as measures of obsessive-compulsive symptoms and beliefs. The compulsive checking group reported greater trait anger, though not greater anger expression, than the student control group. Furthermore, beliefs concerning perfectionism and intolerance of uncertainty were positively correlated with anger expression and trait anger among compulsive checkers but not among the student control group. The implications of these findings are discussed in terms of cognitive behavioural treatments for and models of compulsive checking in OCD. PMID- 17723226 TI - The ND4 G11696A mutation may influence the phenotypic manifestation of the deafness-associated 12S rRNA A1555G mutation in a four-generation Chinese family. AB - We report here the clinical, genetic and molecular characterization of a large Han Chinese family with aminoglycoside-induced and nonsyndromic hearing loss. The penetrance of hearing loss (affected matrilineal relatives/total matrilineal relatives) in this pedigree was 53%, when aminoglycoside-induced deafness was included. When the effect of aminoglycosides was excluded, the penetrance of hearing loss in this pedigree was 42%. These matrilineal relatives exhibited a wide range of severity of hearing loss, varying from profound to normal hearing. Furthermore, these affected matrilineal relatives shared some common features: bilateral hearing loss of high frequencies and symmetries. Sequence analysis of mitochondrial DNA (mtDNA) in the pedigree identified the homoplasmic 12S rRNA A1555G mutation and other 35 variants belonging to Eastern Asian haplogroup D4. Of these, the V313I (G11696A) mutation in ND4 was associated with vision loss. However, the extremely low penetrance of visual loss, and the mild biochemical defect and the presence of one/167 Chinese controls indicted that the G11696A mutation is itself not sufficient to produce a clinical phenotype. Thus, the G11696A mutation may act in synergy with the primary deafness-associated 12S rRNA A1555G mutation in this Chinese family, thereby increasing the penetrance and expressivity of hearing loss in this Chinese pedigree. PMID- 17723227 TI - Characterization, expression and transcriptional regulation of P450c17-I and -II in the medaka, Oryzias latipes. AB - Recently we reported the isolation of two types of cytochrome P450c17s (steroid 17alpha-hydroxylase/C17, 20 lyase) encoded by two different genes, from genomes of teleost fish. In this study, we characterized the expression profile, enzymatic activity and transcriptional regulation of P450c17-I and -II in the medaka ovary. Similar to tilapia, medaka P450c17-I possessed both hydroxylase and lyase activities, while P450c17-II possessed only the hydroxylase activity. In situ hybridization and gene expression profiles during 48h prior to spawning indicated that P450c17-I is responsible for the production of estradiol-17beta during oocyte growth, while P450c17-II for the production of 17alpha, 20beta dihydroxy-4-pregnen-3-one during oocyte maturation and cortisol production in the head kidney. Luciferase assays and expression profiles of transcription factors as revealed by real time PCR suggested that P450c17-I and -II expression are tightly controlled by Ad4BP/SF-1, Lrh-1, Foxl2, and Dax1 during the 48 h prior to spawning. PMID- 17723228 TI - Transcriptional suppression of cytokine-induced iNOS gene expression by IL-13 through IRF-1/ISRE signaling. AB - IL-13 has been reported as one of the major down-regulators of iNOS expression in various tissues and cells. The molecular mechanism of iNOS suppression by IL-13 remains unclear, especially at the transcriptional stage. In this study, we found that IL-13 inhibited the expression of iNOS mRNA, protein, and NO product in a concentration-dependent manner for cytokine-stimulated rat hepatocytes. The most effective dose for IL-13 inhibitory effect is approximately 5 ng/ml. IL-13 also decreased the rat iNOS transcriptional activity by promoter analysis, but had no effect on iNOS mRNA stability. By using TranSignal Protein/DNA Combo Array, we identified cytokine-stimulated IRF-1/ISRE binding that was decreased by the addition of IL-13. Gel shift assay confirmed that IL-13 reduced the IRF-1/ISRE binding at nucleotides -913 to -923 of the rat iNOS promoter. Western blot revealed that IL-13 diminished the relative amount of IRF-1 protein translocated to the nucleus. Our data demonstrate that IL-13 down-regulates the cytokine induced iNOS transcription by decreasing iNOS specific IRF-1/ISRE binding activity. PMID- 17723229 TI - Effect of temperature and pH on 31P nuclear magnetic resonances of phospholipids in cholate micelles. AB - Accurate and precise determination of phospholipid composition by 31P NMR spectroscopy requires correct assignments and adequate spectral resolution. Because temperature and pH may affect chemical shifts (delta), our first aim was to establish the temperature coefficient (Deltadelta/DeltaT) of common phospholipid classes when using sodium cholate as detergent. This parameter can then be used to aid in resonance assignments. The second goal was to investigate the pH dependence of delta so that, in addition to temperature, pH control can be used to minimize spectral overlap. For phosphatidylcholine, sphingomyelin, dihydrosphingomyelin and phosphatidylglycerol, delta values were invariant with pH and temperature. Whereas the Deltadelta/DeltaT for phosphatidylinositol was 4 x 10(-3)ppm/ degrees C, regardless of pH, these coefficients were highly pH dependent for phosphatidic acid, phosphatidylethanolamine and phosphatidylserine, exhibiting maximal variations with the deprotonation of the headgroup, particularly for phosphatidic acid. These trends indicate the importance of H bonding on delta and Deltadelta/DeltaT for phospholipid resonances. PMID- 17723230 TI - Numerical analysis of pulsatile blood flow and vessel wall mechanics in different degrees of stenoses. AB - Hemodynamics factors and biomechanical forces play key roles in atherogenesis, plaque development and final rupture. In this paper, we investigated the flow field and stress field for different degrees of stenoses under physiological conditions. Disease is modelled as axisymmetric cosine shape stenoses with varying diameter reductions of 30%, 50% and 70%, respectively. A simulation model which incorporates fluid-structure interaction, a turbulence model and realistic boundary conditions has been developed. The results show that wall motion is constrained at the throat by 60% for the 30% stenosis and 85% for the 50% stenosis; while for the 70% stenosis, wall motion at the throat is negligible through the whole cycle. Peak velocity at the throat varies from 1.47 m/s in the 30% stenosis to 3.2m/s in the 70% stenosis against a value of 0.78 m/s in healthy arteries. Peak wall shear stress values greater than 100 Pa were found for > or =50% stenoses, which in vivo could lead to endothelial stripping. Maximum circumferential stress was found at the shoulders of plaques. The results from this investigation suggest that severe stenoses inhibit wall motion, resulting in higher blood velocities and higher peak wall shear stress, and localization of hoop stress. These factors may contribute to further development and rupture of plaques. PMID- 17723231 TI - Preparation and evaluation of solid-phase microextraction fibers based on monolithic molecularly imprinted polymers for selective extraction of diacetylmorphine and analogous compounds. AB - All of the studies on solid-phase microextraction based on molecularly imprinted polymers up to now have been carried out on the synthesis of the polymer on the surface of the fiber which is brittle and the polymer coating strips during handling. The objective of this study was to develop a method for fabrication of a monolithic and robust solid-phase microextraction fiber on the basis of molecularly imprinted polymer for selective extraction of diacetylmorphine and its structural analogues followed by their GC or GC/MS analysis. A fiber was produced by copolymerization of methacrylic acid-ethylene glycol dimethacrylate imprinted with diacetylmorphine. The effective factors influencing the polymerization have been investigated and are detailed here. Also, the influences of pH, extraction time and temperature on the extraction efficiency of analytes were investigated. The prepared fiber was thermally stable up to 300 degrees C which has vital importance in SPME coupled with GC or GC/MS. The adsorption isotherm modeling was performed by fitting the data of studied compounds to bi Langmuir isotherm model. The evaluated equilibrium constants for diacetylmorphine were 0.011 and 1824.72 microM(-1), and the number of binding sites was 170.37 and 4.64 nmolg(-1), respectively. This fiber was successfully used for extraction of template molecule from aqueous solution and further analysis with GC or GC/MS. The high extraction efficiency was obtained for diacetylmorphine, 6 monoacetylcodeine, and 6-monoacetylmorphine, yielding the detection limits of 300, 47, and 1 ngmL(-1), respectively. PMID- 17723232 TI - Estimation of adsorption isotherm parameters with inverse method--possible problems. AB - In recent years the inverse method (IM) has been frequently applied to estimate of isotherm parameters. The IM has been used for adsorption process modeling for one, two and even three component chromatography. This method requires only a few injections with various sample concentrations, so the solute consumption and time requirements are very modest. The successful estimation of isotherm parameters with IM depends on applied chromatography column model and a numerical method used to solve the model. For HPLC column the classical equilibrium-dispersive (ED) model can be used. This model is solved frequently with very fast Rouchon finite difference method. However, the accuracy of computations with Rouchon method is decreasing with increase of the number of analyzed components. The aim of this work is the comparison of the results obtained with inverse method when ED model was solved with Rouchon or orthogonal collocation on finite element (OCFE) scheme. Assuming that solution of ED model with OCFE method can be regarded as real a solution, it was found that the Rouchon scheme may not give satisfactory results even for column with 10,000 theoretical plates for three component chromatography. Moreover, the optimal conditions for separation, calculated with Rouchon method, can be remarkably different from that obtained with the OCFE method. The next aim of this work is the presentation of Craig method application to estimation of model parameters with IM. PMID- 17723233 TI - Determination of total cholesterol in serum by high-performance liquid chromatography with electrochemical detection. AB - A simple and sensitive HPLC method that does not require derivatization for determining cholesterol has been developed. Investigation of voltammetric behavior of cholesterol showed that cholesterol could be oxidized on a glassy carbon electrode in non-aqueous solvents. This was applied to the development of a method by HPLC with electrochemical detection (HPLC-ED). The HPLC-ED was optimized using the separation of cholesterol and oxysterols including 26 hydroxycholesterol and 24S-hydroxycholesterol. The separation was carried out with a Develosil C30-UG-3 column; acetonitrile-2-propanol (9:1, v/v) containing 50mM LiClO(4) as a mobile phase; and an applied potential at 1.9V versus Ag/AgCl. The current peak height was linearly related to the amount of cholesterol injected from 0.5-100 microM (r>0.999). The detection limit (S/N=3) of cholesterol was 0.36 microM (1.8 pmol). Cholesterol at 100 microM was directly detected with a relative standard deviation (RSD) of less than 1.0% (n=8). Total cholesterol and free cholesterol in control human serum were determined by the present method with the recovery of more than 90% and the RSD (n=6) of less than 3.0%. PMID- 17723234 TI - Comparison of two sample preconcentration strategies for the sensitivity enhancement of flavonoids found in Chinese herbal medicine in micellar electrokinetic chromatography with UV detection. AB - Two on-column preconcentration techniques named stacking with reverse migrating micelles (SRMM) and anion selective electrokinetic injection and a water plug sweeping with reverse migrating micelles (ASIW-sweep-RMM) were used and compared for concentration and separation of flavonoids in Chinese herbs using reverse migration micellar electrokinetic chromatography (RM-MEKC). The optimal background electrolyte (BGE) used for separation and preconcentration was a solution composed of 20mM phosphoric acid (H(3)PO(4))-100mM sodium dodecyl sulfate (SDS)-20% (v/v) acetonitrile (ACN) buffer (pH 2.0), the applied voltage was -15kV. To achieve reasonable results of the two techniques, the conditions which affected preconcentration were examined. A comparison of used techniques with normal hydrodynamic injection (5s), concerning enhancement factors and limits of detection (LODs) was presented. Under the optimum stacking conditions, about 27-37- and 45-194-fold improvement in the detection sensitivity was obtained for SRMM and ASIW-sweep-RMM, respectively, compared to usual hydrodynamic sample injection (5s). The LODs (S/N=3) for SRMM and ASIW-sweep-RMM in terms of peak height, can reach down to 1.15 x 10(-2) microg/ml for hesperetin and 2.4 x 10(-3) microg/ml for nobiletin, respectively. Finally, the amounts of the six flavonoids in extract of Fructus aurantii Immaturus were successfully determined using ASIW-sweep-RMM. The six analytes were baseline separated with sample matrix under the optimum ASIW-sweep-RMM conditions and the experimental results showed that preconcentration was well achieved after the dilution of sample solutions. PMID- 17723235 TI - A nanoparticle-based solid-phase extraction method for liquid chromatography electrospray ionization-tandem mass spectrometric analysis. AB - A solid-phase extraction (SPE) procedure with the use of superparamagnetic Fe(3)O(4) nanoparticles as extracting agent was developed for HPLC-ESI-MS/MS analysis. Four most heavily used triazine pesticides (herbicides) were taken as the test compounds. The NPs showed an excellent capability to retain the compounds tested, and a quantitative extraction was achieved within 10min under the testing conditions, i.e. 100 microL NP solution was added to 400 mL sample in a beaker with stirring. After extraction, the superparamagnetic NPs were easily collected by using an external magnet. Very importantly, analytes retained on the Fe(3)O(4) NPs could be quantitatively recovered by dissolving the NPs with an HCl solution, allowing subsequent HPLC-ESI-MS/MS quantification. A capillary HPLC-ESI MS/MS method with the present NP-based SPE procedure was developed for the determination of triazines including atrazine, prometryn, terbutryn, and propazine. Atrazine-d(5) was used as internal standard. The method had an LOD of 10 pg/mL atrazine, and a linear calibration curve over a range from 30 pg to 50.0 ng/mL. Simultaneous determination of the four triazine pesticides in water samples taken from local lakes was demonstrated. PMID- 17723236 TI - Effect of metal tolerant plant growth promoting Bradyrhizobium sp. (vigna) on growth, symbiosis, seed yield and metal uptake by greengram plants. AB - The nickel and zinc tolerant plant growth promoting Bradyrhizobium sp. (vigna) RM8 was isolated from nodules of greengram, grown in metal contaminated Indian soils. The plant growth promoting (PGP) potentials of strain RM8 was assessed both in the presence and absence of nickel and zinc under in vitro conditions. Strain RM8 tolerated a high level of nickel (300 microg ml(-1)) and zinc (1400 microg ml(-1)) on yeast extract mannitol agar medium. Bradyrhizobium sp. (vigna) strain RM8 produced 13.3 microg ml(-1) of indole acetic acid in Luria Bertani broth at 100 microg ml(-1) of tryptophan which increased to 13.6 microg ml(-1) at 50 microg Ni ml(-1) and 13.5 microg ml(-1) at 300 microg Zn ml(-1). Strain RM8 was positive for siderophore, HCN and ammonia both in the absence and presence of nickel and zinc. The PGP activity of this strain was further evaluated with increasing concentrations of nickel and zinc using greengram as a test crop. The bioinoculant enhanced the nodule numbers by 82%, leghaemoglobin by 120%, seed yield by 34%, grain protein by 13%, root N by 41% and shoot N by 37% at 290 mg Ni kg(-1) soil. At 4890 mg Zn kg(-1) soil, the bioinoculant increased the nodule numbers by 50%, leghaemoglobin by 100%, seed yield by 36%, grain protein by 13%, root N by 47% and shoot N by 42%. The bioinoculant strain RM8 reduced the uptake of nickel and zinc by plant organs compared to plants grown in the absence of bioinoculant. This study suggested that the bioinoculant due to its intrinsic abilities of growth promotion and attenuation of the toxic effects of nickel and zinc could be exploited for remediation of metal from nickel and zinc contaminated sites. PMID- 17723237 TI - Heavy metals mobility in full-scale bioreactor landfill: initial stage. AB - Selected heavy metals (HMs) including Cd, Cr, Cu, Ni, Pb and Zn initially released from a full-scale bioreactor landfill were monitored over the first 20 months of operation. At the initial landfill stage, the leachate exhibited high HMs release, high organic matter content (27000-43000gl(-1) of TOC) and low pH (5 6). By the fifth month of landfilling, the methanogenic stage had been established, and HMs release was reduced below the Chinese National Standards. Total released HMs accounted for less than 1% of landfill deposited during the investigated period. Most landfill HMs were inorganic. Fourier-transform infrared (FT-IR) spectra data and model calculations using Visual MINTEQ indicated that humic substances strongly affected the mobility of organic fractions of HMs in the methanogenic landfill. The initial rates of HMs release could be enhanced by recycling the leachate back to bioreactor landfill, but the total quantity released may be reduced by early establishment of methanogenic stage in bioreactor landfill. PMID- 17723238 TI - Elevated in-home sediment contaminant concentrations - the consequence of a particle settling-winnowing process from Hurricane Katrina floodwaters. AB - Sediment samples were collected from two homes which were flooded in the wake of Hurricane Katrina in August 2005. The samples were analyzed for trace metals and semi-volatile organic compounds using techniques based on established EPA methods. The data showed higher concentrations of some metals and semi-volatile organic pollutants than reported in previous outdoor sampling events of soils and sediments. The Lake Pontchartrain sediments became resuspended during the hurricane, and this material subsequently was found in the residential areas of New Orleans following levee breaches. The clay and silt particles appear to be selectively deposited inside homes, and sediment contaminant concentrations are usually greatest within this fraction. Re-entry advisories based on outdoor sample concentration results may have under-predicted the exposure levels to homeowners and first responders. All contaminants found in the sediment sampled in this study have their origin in the sediments of Lake Pontchartrain and other localized sources. PMID- 17723239 TI - Absorption of polycyclic aromatic hydrocarbons to cellulose. AB - Polycyclic aromatic hydrocarbons (PAHs) are widespread toxic chemicals. The environmental fate of these chemicals is in part controlled by sorption to (organic matter in) sediments and soils. One of the most abundant organic matter compounds on earth is cellulose. Remarkably, sorption of PAHs to cellulose has hardly been studied; only two reports on the binding of some low-molecular-weight PAHs exist in the literature. In this study, sorption of PAHs to cellulose was investigated in more detail, by measuring isotherms for a series of 13 PAHs, covering a wide hydrophobicity range. The results indicated that sorption of PAHs to cellulose is a linear partition process for all PAHs investigated (phenanthrene-indeno[1,2,3-cd]pyrene). The affinity of PAHs for cellulose appeared to be about 400 times lower than for octanol and even up to 300000 times lower than for black carbon or coal. Linked to the estimated yearly production of cellulose and black carbon, these results suggest that cellulose is probably not a major environmental sorption domain for PAHs. PMID- 17723240 TI - The three-dimensional structure of 3,3',4,4'-tetrachlorobiphenyl, a dioxin-like polychlorinated biphenyl (PCB). AB - The crystal structure of PCB 77 (3,3',4,4'-tetrachlorobiphenyl, C(12)H(6)Cl(4)), a dioxin-like PCB congener, is described. The dihedral angle of PCB 77 is 43.94(6) degrees, which is slightly larger than calculated or experimental dihedral angles of biphenyl derivatives in solution but smaller than experimental dihedral angles in the gas phase. PMID- 17723241 TI - Structure and activity of apoferritin-stabilized gold nanoparticles. AB - A simple method for synthesizing gold nanoparticles stabilized by horse spleen apoferritin (HSAF) is reported using NaBH(4) or 3-(N-morpholino)propanesulfonic acid (MOPS) as the reducing agent. AuCl(4)(-) reduction by NaBH(4) was complete within a few seconds, whereas reduction by MOPS was much slower; in all cases, protein was required during reduction to keep the gold particles in aqueous solution. Transmission electron microscopy (TEM) showed that the gold nanoparticles were associated with the outer surface of the protein. The average particle diameters were 3.6 and 15.4 nm for NaBH(4)-reduced and MOPS-reduced Au HSAF, respectively. A 5-nm difference in the UV-Vis absorption maximum was observed for NaBH(4)-reduced (530 nm) and MOPS-reduced Au-HSAF (535 nm), which was attributed to the greater size and aggregation of the MOPS-reduced gold sample. NaBH(4)-reduced Au-HSAF was much more effective than MOPS-reduced Au-HSAF in catalyzing the reduction of 4-nitrophenol by NaBH(4), based on the greater accessibility of the NaBH(4)-reduced gold particle to the substrate. Rapid reduction of AuCl(4)(-) by NaBH(4) was determined to result in less surface passivation by the protein. Methods for studying ferritin-gold nanoparticle assemblies may be readily applied to other protein-metal colloid systems. PMID- 17723243 TI - [FeIII(SR)4]1- complexes can be synthesized by the direct reaction of thiolates with FeCl3. AB - It is shown that the previously characterized [Fe(III)(SR)(4)](1-) (R=Et, i-Pr, Ph) complexes can be synthesized by the direct reaction of 4equiv. of LiSR with FeCl(3) in DMF solution. [Fe(III)(SR)(4)](1-) complexes are synthetic analogs for the [Fe(III)(S-Cys)(4)] center in rubredoxin proteins. PMID- 17723242 TI - Only one of a wide assortment of manganese-containing SOD mimicking compounds rescues the slow aerobic growth phenotypes of both Escherichia coli and Saccharomyces cerevisiae strains lacking superoxide dismutase enzymes. AB - A variety of manganese-containing coordination compounds, frequently termed superoxide dismutase (SOD) mimics, have been reported to have SOD activity in vitro and to be effective at improving conditions related to increased oxidative stress in multicellular organisms. We tested the effectiveness of several of these compounds in substituting for authentic SOD enzymes in two simple systems- the prokaryote Escherichia coli and the single-celled eukaryote, Saccharomyces cerevisiae--where strains are available that completely lack cytoplasmic SOD activity and are thus significantly impaired in their ability to grow aerobically. Most of the compounds tested, including Euk-8 and Euk-134, manganese salen derivatives developed by Eukarion; M40403, a manganese complex of a bis(cyclohexylpyridine)-substituted macrocyclic ligand developed by Metaphore; and several manganese porphyrin derivatives, were ineffective in both systems. Only the manganese tetrapyridyl porphyrin complex MnTM-2-PyP and two close relatives were effective in rescuing aerobic growth of E. coli lacking SOD, and, in the case of sod1Delta yeast, only MnTM-2-PyP itself was fully effective. Surprisingly, several compounds reported to be beneficial in other in vivo model systems (Euk-8, Euk-134, M40403) were actually toxic to these organisms lacking SOD, although they had no effect on the wild-type parent strains. Our results suggest the possibility that the beneficial effects of some of the so-called "SOD mimic drugs" may be due to some property other than in vivo superoxide dismutase activity. PMID- 17723244 TI - DFT study on the reactivity of iron porphyrins tuned by ring substitution. AB - The effect of beta-substituents (-NO2, -Br, -OCH3) in the reactivity of Fe(II) and Fe(III) porphyrins is studied by means of density functional theory (DFT) calculations. The binding of nitric oxide, carbon monoxide and dioxygen (NO, CO, O2) was explored due to the relevance of their interactions in the chemistry of heme proteins and in biomimetic catalysis. The binding capability (BC) of the porphyrins was found to be strongly modulated both by the donor and attractor substituents used in the work. Unexpectedly, we found that the BC of Fe(II) porphyrins is mainly decreased for the diatomic ligands, when both donor or withdrawing substituents were considered. This effect was particularly significant when the ligand was oxygen. The correlation of Fe-X and X-O (X=N, C, O) bond distances is explained in terms of backdonation effects. PMID- 17723245 TI - Computational studies of modified [Fe3S4] clusters: why iron is optimal. AB - This work reports density functional computations of metal-substituted models of biological [Fe3S4] clusters in oxidation states [MFe2S4](+/0/-1) (M=Mn, Fe, Co, Ni, Cu, Zn, and Mo). Geometry optimization with a dielectric screening model is shown to provide a substantial improvement in structure, compared to earlier used standard procedures. The error for average Fe-S bonds decreased from 0.038A to 0.016A with this procedure. Four density functionals were compared, B3LYP, BP86, TPSS, and TPSSh. B3LYP and to a lesser extent TPSSh energies were inconsistent with experiment for the oxidized [Fe3S4]+ cluster. BP86 (and to a slightly lesser extent TPSS) was within expected theoretical and experimental uncertainties for all oxidation states, the only qualitative error being 5kJ/mol in favor of the M(S)=3/2 configuration for the [Fe3S4]+ cluster, so BP86 was used for quantitative results. Computed reorganization energies and reduction potentials point directly towards the [Fe3S4] cluster as the superior choice of electron carrier, with the [ZnFe2S4] cluster a close second. In addition, partially and fully Mo-substituted clusters were investigated and found to have very low reorganization energies but too negative reduction potentials. The results provide a direct rationale why any substitution weakens the cluster as an electron carrier, and thus why the [Fe3S4] composition is optimal in the biological clusters. PMID- 17723246 TI - Histopathology, parasite density and cell phenotypes of the popliteal lymph node in canine visceral leishmaniasis. AB - While enlargement of popliteal lymph nodes (LN) is frequently described in canine visceral leishmaniasis (CVL), there are few histopathologic studies of lymph nodes during this chronic immunopathological condition. Besides a detailed histopathologic analysis, we have characterized the parasite load and major immunophenotypic features of the LN in Leishmania (Leishmania) chagasi-infected dogs. Our major histopathological findings highlight that hypertrophy/hyperplasia of LN cortical and medullary zones was the principal characteristic observed in asymptomatic dogs (AD), whereas atrophy of LN cortical zone was predominant in symptomatic animals (SD). The LN parasite density detected by anti-Leishmania immunohistochemical assay or expressed as Leishman Donovan Units was also highly correlated with the skin parasitism, the most reliable parameter to decode the clinical status of CVL. The major LN immunophenotypic changes during ongoing CVL were an increased frequency of T-lymphocytes, particularly CD8+ T-cells, up regulation of MHC-II expression by lymphocytes and decreased levels of CD21+ B cells. Our findings further demonstrated that changes in the LN B-lymphocyte compartment exhibited a negative correlation with the skin parasite load. Conversely, we also showed evidence for a positive association between skin parasitism and LN T-cell-mediated immunity, suggesting that T-cells, especially CD8+ lymphocytes, may have a Type-2 immunological profile in this lymphoid tissue in response to CVL. PMID- 17723247 TI - PRISMA-7: a case-finding tool to identify older adults with moderate to severe disabilities. AB - Many comprehensive rating scales have been developed to assess disabilities. These assessments, which require significant amounts of time, are usually performed by trained professionals. A simple case-finding instrument is needed to quickly identify older persons with potential disabilities, who then should undergo comprehensive assessments. In a cross-sectional study of 594 community dwelling older subjects, we developed a questionnaire from an initial list of 23 yes/no questions, and compared it with an existing one to determine their relative ability to identify older persons with moderate to severe disabilities. Initially designed to identify older people with any disability, the existing seven-question tool also provided to be a good marker of significant disabilities, with a cut-off score of three or more positive answers. The sensitivity and specificity of this cut-off are 78.3% and 74.7%, respectively. These validity indices support the use of this questionnaire in identifying older persons with potential moderate to severe disabilities with a view to referring them for more comprehensive assessment. PMID- 17723248 TI - Wide distribution and subcellular localization of histamine in sympathetic nervous systems of different species. AB - Previous studies have demonstrated that histamine (HA) acts as a neurotransmitter in the cardiac sympathetic nervous system of the guinea pig. The aim of the current study was to examine whether HA widely exists in the sympathetic nervous systems of other species and the subcellular localization of HA in sympathetic terminals. An immunofluorescence histochemical multiple-staining technique and anterograde tracing method were employed to visualize the colocalization of HA and norepinephrine (NE) in sympathetic ganglion and nerve fibers in different species. Pre-embedding immunoelectron microscopy was used to observe the subcellular distribution of HA in sympathetic nerve terminals. Under the confocal microscope, coexistence of NE and HA was displayed in the superior cervical ganglion and celiac ganglion neurons of the mouse and dog as well as in the vas deferens, mesenteric artery axon, and varicosities of the mouse and guinea pig. Furthermore, colocalization of NE and HA in cardiac sympathetic axons and varicosities was labeled by biotinylated dextranamine injected into the superior cervical ganglion of the guinea pig. By electron microscopy, HA-like high-density immunoreactive products were seen in the small vesicles of the guinea pig vas deferens. These results provide direct cellular and subcellular morphological evidence for the colocalization of HA and NE in sympathetic ganglion and nerve fibers, and support that HA is classified as a neurotransmitter in sympathetic neurons. PMID- 17723249 TI - Ethanol tolerance and the variation of plasma membrane composition of yeast floc populations with different size distribution. AB - The ethanol tolerance of a self-flocculating yeast strain SPSC01 was investigated in an oxygen-limited fed-batch bioreactor. Employing Focused Beam Reflectance Measurement (FBRM) on-line monitoring system, four yeast floc populations with the average size ranging from 100 to 400mum were obtained. It was found that ethanol tolerance increased with the increasing floc size in the 100, 200, and 300mum floc populations, while increasing the average floc size further to 400mum resulted in lower ethanol tolerance. Examination of the membrane composition of different floc populations revealed that the plasma membrane composition of the floc populations was significantly different in the contents of ergosterol, phosphatidylinositol, as well as phospholipid palmitoleic acid. What's more, the plasma membrane of more ethanol tolerant floc population was less permeable when subjected to 15% (v/v) ethanol shock treatment, and the plasma membrane ATPase activities were higher in the floc populations with higher ethanol tolerance. These results indicate that the average size distribution of the floc populations exerted great influence on the physiological status of yeast cells during the ethanol production process, leading to the changes in plasma membrane composition that contributed to improved ethanol tolerance in self-flocculating yeast SPSC01. PMID- 17723250 TI - Systematic review of baseline low-dose CT lung cancer screening. AB - The purpose of this systematic review was to provide physicians and patients with a synthesis of the available data and an assessment of the operating characteristics associated with baseline LDCT screening for lung cancer. Various databases, meeting abstracts, clinical trials in progress, and major textbooks for relevant data from 1966 to 2006 were searched for relevant studies. The median value of sensitivity, specificity, positive predictive value and negative predictive value were 81%, 81%, 8% and 99%, respectively. Of the studies that compared LDCT with other lung cancer screening maneuvers, it was found that LDCT detected a greater number of cancerous nodules. On average, 80% of lung cancers detected by baseline LDCT screening were categorized as Stage I cancers. Current data demonstrate that both the operating characteristics of baseline LDCT screening and the relatively high proportion of Stage I cancers detected with LDCT may potentially lead to effective screening programs. However, evidence of reduced mortality and morbidity with the use of LDCT is not established. Therefore, LDCT for lung cancer screening should be considered as investigative and needs to be confirmed by well-designed randomized controlled trials prior to community and institutional implementation. PMID- 17723251 TI - Computational identification and analysis of immune-associated nucleotide gene family in Arabidopsis thaliana. AB - GTP-binding proteins represent a ubiquitous regulatory mechanism in controlling growth and development in eukaryotes under normal and stress conditions. The IAN/GIMAP proteins belong to a novel family of functionally uncharacterized GTP binding proteins expressed in both plant and vertebrate cells during anti pathogenic responses. To gain novel insights into their roles in plants, we did genome-wide analysis of the IAN/GIMAP gene family. We identified 13 Arabidopsis IAN/GIMAP genes, which share similar gene structures and mostly reside in a tandem cluster on chromosomes. Sequence comparison reveals that these genes encode 26-52 kDa proteins with one GTP-binding domain and a conserved box unique to the family. Phylogenetic analysis suggests that the IAN/GIMAP genes of angiosperms and vertebrates may have evolved by independent gene duplication events. GENEVESTIGATOR sources were mined for comprehensive and comparative Arabidopsis IAN/GIMAP gene family expression analysis. These data reveal that IAN/GIMAPs exhibit diverse expression patterns during development and in response to external stimuli, indicating that these paralogous genes are likely involved in complex biological processes in Arabidopsis. Our present findings provide a basis for elucidating the novel GTPase family protein-mediated regulatory mechanisms in the future. PMID- 17723252 TI - Comparative salt tolerance analysis between Arabidopsis thaliana and Thellungiella halophila, with special emphasis on K(+)/Na(+) selectivity and proline accumulation. AB - The eco-physiology of salt tolerance, with an emphasis on K(+) nutrition and proline accumulation, was investigated in the halophyte Thellungiella halophila and in both wild type and eskimo-1 mutant of the glycophyte Arabidopsis thaliana, which differ in their proline accumulation capacity. Plants cultivated in inert sand were challenged for 3 weeks with up to 500mM NaCl. Low salinity significantly decreased A. thaliana growth, whereas growth restriction was significant only at salt concentrations equal to or exceeding 300mM NaCl in T. halophila. Na(+) content generally increased with the amount of salt added in the culture medium in both species, but T. halophila showed an ability to control Na(+) accumulation in shoots. The analysis of the relationship between water and Na(+) contents suggested an apoplastic sodium accumulation in both species; this trait was more pronounced in A. thaliana than in T. halophila. The better NaCl tolerance in the latter was associated with a better K(+) supply, resulting in higher K(+)/Na(+) ratios. It was also noteworthy that, despite highly accumulating proline, the A. thaliana eskimo-1 mutant was the most salt-sensitive species. Taken together, our findings indicate that salt tolerance may be partly linked to the plants' ability to control Na(+) influx and to ensure appropriate K(+) nutrition, but is not linked to proline accumulation. PMID- 17723253 TI - K(+) starvation inhibits water-stress-induced stomatal closure. AB - The effect of potassium starvation on stomatal conductance was studied in olive trees and sunflower plants, two major crops with greatly differing botanical characteristics. In both species, K(+) starvation inhibited water-stress-induced stomatal closure. In olive trees, potassium starvation favoured stomatal conductance and transpiration, as well as inhibiting shoot growth, in the three cultivars studied: 'Lechin de Granada', 'Arbequina' and 'Chetoui'. However, 'Lechin de Granada' - generally considered more drought-tolerant than 'Arbequina' and 'Chetoui' - proved less susceptible to potassium starvation. Results for olive trees also suggest genetic variability in olive cultivars in relation to potassium requirements for stem growth and the regulation of water transpiration. The results obtained suggest that inhibition of the stomatal closure mechanism produced by moderate potassium starvation is a widespread plant physiological disorder, and may be the cause of tissue dehydration in many water-stressed crops. PMID- 17723254 TI - Hand hygiene monitoring: what it really measures. PMID- 17723256 TI - MRI-based registration of pelvic alignment affected by altered pelvic floor muscle characteristics. AB - BACKGROUND: Pelvic floor muscles have potential to influence relative pelvic alignment. Side asymmetry in pelvic floor muscle tension is claimed to induce pelvic malalignment. However, its nature and amplitude are not clear. There is a need for non-invasive and reliable assessment method. An intervention experiment of unilateral pelvic floor muscle activation on healthy females was performed using image data for intra-subject comparison of normal and altered configuration of bony pelvis. METHODS: Sequent magnetic resonance imaging of 14 females in supine position was performed with 1.5 T static body coil in coronal orientation. The intervention, surface functional electrostimulation, was applied to activate pelvic floor muscles on the right side. Spatial coordinates of 23 pelvic landmarks were localized in each subject and registered by specially designed magnetic resonance image data processing tool (MPT2006), where individual error calculation; data registration, analysis and 3D visualization were interfaced. FINDINGS: The effect of intervention was large (Cohen's d=1.34). We found significant differences in quantity (P<0.01) and quality (P=0.02) of normal and induced pelvic displacements. After pelvic floor muscle activation on the right side, pelvic structures shifted most frequently to the right side in ventro caudal direction. The right femoral head, the right innominate and the coccyx showed the largest displacements. INTERPRETATION: The consequences arising from the capacity of pelvic floor muscles to displace pelvic bony structures are important to consider not only in management of malalignment syndrome but also in treatment of incontinence. The study has demonstrated benefits associated with processing of magnetic resonance image data within pelvic region with high localization and registration reliability. PMID- 17723255 TI - Clinical and pathological features of an Alzheimer's disease patient with the MAPT Delta K280 mutation. AB - We identified a case of Alzheimer's disease with a deletion of the lysine residue at codon 280 (DeltaK280) in exon 10-encoded microtubule-binding repeat domain of the tau gene (MAPT). This mutation was originally identified in a sporadic case of frontotemporal dementia (FTD) with a family history of Parkinson's disease. In the original report, the authors were careful in their assessment of the pathogenicity and suggested one could not be sure whether the mutation was pathogenic or not. The mutation has always presented a conundrum because it is the only known mutation, of assumed pathogenicity, which increases the proportion of 3-repeat tau mRNA in in vitro assays. Here we present the clinical and pathological features of a new case with this mutation and discuss whether the mutation is indeed pathogenic. PMID- 17723258 TI - Safety assessment of hydroxypropyl methylcellulose as a food ingredient. AB - Hydroxypropyl methyl cellulose (HPMC; CAS No. 9004-65-3) is an odorless and tasteless, white to slightly off-white, fibrous or granular, free-flowing powder that is a synthetic modification of the natural polymer, cellulose. It is used in the food industry as a multipurpose food ingredient. HPMC is approved by FDA as both a direct and an indirect food additive, and is approved for use as a food additive by the EU. The JECFA has evaluated the food uses of HPMC and established an acceptable daily intake (ADI) of 'not specified' for such uses. Based on the no-observed-adverse-effect level (NOAEL) of 5000 mg/kg body weight/day from a 90 day feeding study in rats, a tolerable intake for ingestion of HPMC by humans of 5 mg/kg body weight/day is posited and, as such, is more than 100-fold greater than the estimated current consumption of 0.047 mg/kg body weight/day. PMID- 17723257 TI - In vivo effects of partial electrothermal shrinkage on mechanical properties of the anterior cruciate ligament in rabbits. AB - BACKGROUND: No studies have been conducted to clarify an in vivo remodeling of the radiofrequency-treated lesion of the anterior cruciate ligament. The purpose was to determine in vivo effects of radiofrequency shrinkage on mechanical properties of the anterior cruciate ligament. METHODS: Thirty skeletally mature rabbits were used. In each group, radiofrequency energy set at non-ablative levels was applied to the posterolateral bundle of the anterior cruciate ligament with a bipolar radiofrequency generator. All animals were sacrificed at 0, 6, and 12 weeks after surgery, respectively. In each group, 7 and 3 out of the 10 specimens were used for biomechanical and histological evaluations. FINDINGS: After shrinkage treatment, the anterior-posterior translation of the knee and the length of the posterolateral bundle were significantly reduced immediately after surgery, but that this effect disappeared at 6 weeks. The tensile strength and the tangent modulus of the treated bundle were significantly lower than that of the normal control bundle at each period. In addition, the tensile strength and the tangent modulus measured at 12 weeks were significantly lower than that at 0 week. Histological examination showed granulation-like tissues with numerous plump fibroblasts and inflammatory cells were dominantly found in the midsubstance of the posterolateral bundle at 12 weeks. INTERPRETATIONS: This result suggested that the anterior cruciate ligament tissue shortened with the radiofrequency treatment is elongated gradually over time. The mechanical properties of the posterolateral bundle of the anterior cruciate ligament reduced by the radiofrequency shrinkage are not restored in vivo, but significantly deteriorated with time. PMID- 17723259 TI - Informing common pool resource problems: a survey of preference for catchment management strategies amongst farmers and the general public in the Ythan river catchment. AB - In principle the protection of environmental resources is in every ones interest, yet it is evident that this is not what often occurs. In some cases there is an identifiable person or corporation, whose environmental impact can be tractably regulated either politically or via market forces. In other cases there is cumulative impact on a commonly held or "common pool" resource, from a variety of users, making establishing rights and responsibilities for resource management more difficult. The water of the Ythan catchment is one such 'Common Pool Resource' (CPR). An intensively farmed catchment also sustaining a sizable population, the consequent nitrate inputs to the water are believed to be the cause of algal matting at the estuary mouth, an internationally designated wildlife reserve. This led to its designation as Scotland's first Nitrate Vulnerable Zone (NVZ). Supported by the EU Life Environment fund, the Ythan Project attempted to foster co-operation between farmers and the wider community of the Ythan catchment to protect and restore the river environment. Throughout the project surveys were undertaken concerning the popularity of the Ythan Project's voluntary approach compared with more individualist or state-organised approaches. Taking CPR theory as a framework, key findings from those surveys are presented and discussed as to their implications for organisational intervention in CPR problems. PMID- 17723260 TI - Robust detection protocols for uncertain introductions of invasive species. AB - Two important features of real-world port inspections of shipping containers for invasive species are the general absence of underlying economic considerations and the climate of severe uncertainty that surrounds the likelihood of invasive species introductions. In this article we propose and illustrate a method for determining inspection protocols that address both of these issues. We seek inspection protocols that are robust in the sense that they maximize the range of uncertainty over which the expected loss from the introduction of an invasive species plus the costs of inspections do not exceed some critical value. These inspection strategies are practical and provide ready alternatives to existing protocols. PMID- 17723261 TI - The origin of autonomous agents by natural selection. AB - We propose conditions in which an autonomous agent could arise, and increase in complexity. It is assumed that on the primitive Earth there arose a recycling flow-reactor containing spontaneously formed oil droplets or lipid aggregates. These droplets grew at a basal rate by simple incorporation of lipid phase material, and divided by external agitation. This type of system was able to implement a natural selection algorithm once heredity was added. Macroevolution became possible by selection for rarely occurring chemical reactions that produced holistic autocatalytic molecular replicators (contained within the aggregate) capable of doubling at least as fast as the lipid aggregate, and which were also capable of benefiting the growth of its lipid aggregate container. No nucleotides or monomers capable of modular heredity were required at the outset. To explicitly state this hypothesis, a computer model was developed that employed an artificial chemistry, exhibiting conservation of mass and energy, incorporated within each individual of a population of lipid aggregates. This model evolved increasingly complex self-sustaining processes of constitution, a result that is also expected in real chemistry. PMID- 17723262 TI - Microwave assisted facile synthesis of {1/1,3-bis/1,3,5-tris-[(2 nitroxyethylnitramino)-2,4,6-trinitrobenzene]} using bismuth nitrate pentahydrate as an eco-friendly nitrating agent. AB - 1-(2-Nitroxyethylnitramino)-2,4,6-trinitrobenzene (3a), 1,3-bis(2-nitroxyethyl nitramino)-2,4,6-trinitrobenzene (3b) and 1,3,5-tris(2-nitroxyethylnitramino) 2,4,6-trinitrobenzene (3c) were prepared by the nitration of 1-(2 hydroxyethylamino)-2,4,6-trinitrobenzene (2a) 1,3-bis(2-hydroxyethylamino)-2,4,6 trinitrobenzene (2b) and 1,3,5-tris(2-hydroxyethylamino)-2,4,6-trinitrobenzene (2c) using bismuth nitrate pentahydrate (eco-friendly nitrating agent) in tetrahydrofuran adsorbed on silica gel under microwave irradiation, respectively. Key intermediate compounds viz., 2a, 2b and 2c were synthesized by condensing picryl chloride, styphnyl chloride and 1,3,5-trichloro-2,4,6-trinitrobenzene with ethanol amine, respectively, based on the lines of the reported method. The synthesized compounds were characterized based on their physical constant, infrared (IR) spectroscopy and (1)H nuclear magnetic resonance (NMR) spectroscopy. The spectroscopic data obtained indicated the formation of nitrate esters (3a-3c). The nitration methodology adopted in the present study is of relevance in the context of green chemistry. The target compounds (3a-3c) synthesized using eco-friendly approach are of interest from the point of high energy materials (HEMs). PMID- 17723263 TI - Solid phase extraction of heavy metal ions in environmental samples on multiwalled carbon nanotubes. AB - Multiwalled carbon nanotubes (MWNTs) were used as solid phase extractor for Cu(II), Cd(II), Pb(II), Zn(II), Ni(II) and Co(II) ions as ammonium pyrrolidine dithiocarbamate (APDC) chelates, in the present study. The influences of the experimental parameters including pH of the solutions, amounts of MWNTs, amounts of APDC, eluent type and volume, sample volume etc. on the quantitative recoveries of analyte ions were investigated. The effects of matrix ions of natural waters and some transition metals on the recoveries of the analyte ions were also examined in the model solutions. Tests of addition/recovery for analyte ions in real samples were performed with satisfactorily results. The detection limits (3s) for the analyte ions were in the range of 0.30-0.60 microg l(-1). The concentrations of analytes in standard reference materials (NIST RM 8418 Wheat gluten, LGC 6010 Hard drinking water and NIST SRM 1515 Apple leaves) pretreated by the presented method were measured with FAAS and the analytical values were well agreed with the certified values and the reference values without the interference of major components. The presented method has been applied to the determination of analytes in food and environmental samples with satisfactory results. PMID- 17723264 TI - Ultrasonic degradation of Rhodamine B in aqueous solution: influence of operational parameters. AB - The aim of the study was to investigate decolorization of Rhodamine B (RB) in aqueous solution using ultrasonic degradation. The results showed that decolorization follows pseudo-first-order reaction kinetics. The apparent reaction rate constant (kap) was found to increase with decreasing pH and decreases with increasing initial RB concentration. Power density was very important parameter and increasing it causes a considerable increase of removal efficiency. UV-vis spectral changes of RB indicate that in the sonolysis of RB, the cleavage of aromatic chromophore ring structure and the N-deethylation take place, but decomposition of aromatic structure is predominant. PMID- 17723265 TI - Activation of c-jun in the rat basilar artery after subarachnoid hemorrhage. AB - Subarachnoid hemorrhage (SAH) initiates a series of cellular and molecular events, some of which involve a mitogen activated protein kinase, c-jun N terminal kinase (JNK). However, precise details regarding activation of c-jun in the vessel wall after SAH largely remain to be elucidated. In this study, we therefore investigated the localization and time-dependent expression of c-jun in the rat basilar artery after SAH in a rat single-hemorrhage model featuring infusion of autologous arterial blood. Basilar arteries were obtained at 2, 6 and 12h and 1, 2, 4 and 7 days after SAH, as well as from controls. Western blot analysis with c-jun, phosphorylated c-jun at Ser(63), and actin antibodies revealed that c-jun was immediately phosphorylated at Ser(63) within 2h, thereafter gradually becoming dephosphorylated, while total c-jun and actin levels remained almost unchanged. Immunohistochemistry demonstrated phosphorylation of c-jun at Ser(63) to occur in smooth muscle cells of the basilar artery 2h after SAH. These results indicate that c-jun is activated in the basilar artery immediately after the onset of SAH, presumably resulting in transcription of immediate early genes and smooth muscle cell proliferation. PMID- 17723267 TI - Immunohistochemical localization of TRPC6 in the rat substantia nigra. AB - Transient receptor potential channels (TRPC) are plasma membrane, nonselective cationic channels and have been proposed as candidates involved in the regulation of cellular Ca2+ influx [D.E. Clapham, L.W. Runnels, C., Strubing, The TRP ion channel family, Nat. Rev. Neurosci. 2 (2001) 387-396; A. Martorana, C. Giampa, Z. DeMarch, M.T. Viscomi, S. Patassini, G. Sancesario, G. Bernardi, F.R. Fusco, Distribution of TRPC1 receptors in dendrites of rat substantia nigra: a confocal and electron microscopy study, Eur. J. Neurosci. 24 (2006) 732-738]. Studies on regional localization patterns of TRPCs are necessary to provide helpful guidelines for correlating current types with particular channels. In this study, we examined the distribution of one particular member of TRPC superfamily, namely, TRPC6, in the substantia nigra of normal rat brain. Single and double label immunohistochemistry were employed to perform both light and confocal microscopy observations. Our single label studies showed that, in the substantia nigra, TRPC6 labeled the perikarya with a diffuse and intense immunoreaction product distributed throughout cell cytoplasm whereas only a light immunostaining was observed in the cell nuclei. No labeling of axon or terminals was observed, although TRPC6 was evenly distributed in the neuropil. Our dual label studies showed a TRPC6 immunoreactivity pattern that was localized into the proximal dendrites and axon hillock of the large dopaminergic neurons identified by TH immunoreaction. Furthermore, our double label immunofluorescence study for TRPC6 and mGluR1 showed a complete co-localization of the two markers in the substantia nigra. Moreover, TRPC6 did not co-localize with synaptophysin. Thus, our study shows the postsynaptic localization of TRPC6 and its association with mGluR1 in the midbrain dopamine neurons. PMID- 17723266 TI - Isoflurane preconditioning inhibited isoflurane-induced neurotoxicity. AB - The commonly used inhaled anesthetic isoflurane has been shown to be both neuroprotective and neurotoxic in various cell cultures and animal models. We hypothesize that, like cerebral ischemia, isoflurane is inherently neurotoxic. Limited exposure of isoflurane provides neuroprotection via induction of endogenous neuroprotective mechanisms (preconditioning), while prolonged exposure of isoflurane induces neurotoxicity directly by its inherent neurotoxic effects. To test this hypothesis, we treated rat primary cortical neurons at different days in vitro (DIV) and rat pheochromocytoma neurosecretory (PC12) cells with or without Alzheimer's mutated presenilin-1 (PS1) with 2.4% isoflurane for 24 h to induce cell damage determined by both MTT (3-(4,5-dimethyithiazol-2-yl)-2,5 diphenyl-tetrazolium bromide) reduction and LDH (lactate dehydrogenase) release assays. For isoflurane preconditioning, we treated the above cells with isoflurane at 0.6%, 1.2% and 2.4% for 60 min, 4 h prior to a prolonged exposure of 2.4% isoflurane for 24 h. One hour of preconditioning with isoflurane dose dependently inhibited neurotoxicity induced by 2.4% isoflurane for 24 h in both primary cortical neurons and PC12 cells. This neuroprotection was most dramatically observed in matured cortical neurons (DIV 16) and PC12 cells with over expression of Alzheimer's mutated PS1 (L286V). Preconditioning L286V PC12 cells with equivalent two minimal alveolar concentrations (MAC) of halothane (1.5%), but not sevoflurane (4%), also abolished the neurotoxicity induced by 2.4% isoflurane for 24 h. Overall, these results suggest that isoflurane may be both neuroprotective and neurotoxic, depending on the exposure concentrations and duration. PMID- 17723268 TI - Poly(ADP-ribose) polymerase-1 is involved in the neuronal death induced by quinolinic acid in rats. AB - Reactive oxygen and nitrogen species formation leads to DNA damage in animals treated with quinolinic acid. Poly(ADP-ribose) polymerase-1 (PARP-1) is a protein involved in the DNA base excision repair system. Its overactivation promotes cellular energy deficit and necrosis. Here, we evaluated the effect of PJ-34, a potent inhibitor of PARP-1, on the neuronal damage induced by quinolinic acid. Animals were administered with PJ-34 (10 mg/kg, i.p.), 1 h before and 1 h after a striatal infusion of 1 microl of quinolinic acid (240 nmol). PJ-34 clearly attenuated the circling behavior produced by quinolinic acid and completely prevented the histological damage induced by the toxin. The protective effect of PJ-34 suggests that PARP-1 activation is playing an active role in the neuronal death induced by quinolinic acid. PMID- 17723269 TI - Cholinergic modulation of intrinsic fibre-evoked excitatory transmission contains a nicotinic component in immature but not adult rat piriform cortex, in vitro. AB - The piriform cortex (PC) is highly prone to epileptogenesis, particularly in immature animals, where decreased muscarinic modulation of PC intrinsic fibre excitatory neurotransmission is implicated as a likely cause. However, whether higher levels of acetylcholine (ACh) release occur in immature vs. adult PC remains unclear. We investigated this using in vitro extracellular electrophysiological recording techniques. Intrinsic fibre-evoked extracellular field potentials (EFPs) were recorded from layers II to III in PC brain slices prepared from immature (P14-18) and adult (P>40) rats. Adult and immature PC EFPs were suppressed by eserine (1 microM) or neostigmine (1 microM) application, with a greater suppression in immature (approximately 40%) than adult (approximately 30%) slices. Subsequent application of atropine (1 microM) reversed EFP suppression, producing supranormal (approximately 12%) recovery in adult slices, suggesting that suppression was solely muscarinic ACh receptor-mediated and that some 'basal' cholinergic 'tone' was present. Conversely, atropine only partially reversed anticholinesterase effects in immature slices, suggesting the presence of additional non-muscarinic modulation. Accordingly, nicotine (50 microM) caused immature field suppression (approximately 30%) that was further enhanced by neostigmine, whereas it had no effect on adult EFPs. Unlike atropine, nicotinic antagonists, mecamylamine and methyllycaconitine, induced immature supranormal field recovery (approximately 20%) following anticholinesterase-induced suppression (with no effect on adult slices), confirming that basal cholinergic 'tone' was also present. We suggest that nicotinic inhibitory cholinergic modulation occurs in the immature rat PC intrinsic excitatory fibre system, possibly to complement the existing, weak muscarinic modulation, and could be another important developmentally regulated system governing immature PC susceptibility towards epileptogenesis. PMID- 17723270 TI - Identification and characterization of SMI32-immunoreactive amacrine cells in the mouse retina. AB - Mammalian neurons express the neural intermediate filament protein neurofilament (NF). In the retina, NFs have been detected primarily in the axons and processes of retinal ganglion and horizontal cells. We found an amacrine cell type that was immunolabeled with an antibody against SMI32, a non-phosphorylated epitope on neurofilament proteins of high molecular weight, in the mouse retina. This type of amacrine cell was non-randomly distributed, and these cells exhibited a central-peripheral density gradient. Most of these cells co-expressed GABA and ChAT, but not glycine or any other amacrine cell marker. These results suggest that some SMI32-immunoreactive amacrine cells belong to a GABAergic population, and that SMI32 can therefore be used as a marker for a subset of amacrine cells in addition to ganglion cells and horizontal cells in the mouse retina. PMID- 17723272 TI - 1H magnetic resonance spectroscopy study of thalamus in treatment resistant depressive patients. AB - Treatment-resistant depression (TRD) is a common clinical problem, and represents a considerable challenge to treatment, however, the pathogenesis of this disease is poorly understood. Thalamus is generally believed to have a role in the pathophysiology of depression. In this study, we adopted 1.5T (1)H magnetic resonance spectroscopy ((1)H MRS) to examine possible alterations of thalamus metabolism in 20 adult TRD patients. Our results suggested there might be damage and loss of neurons, as well as membrane phospholipids associated metabolism abnormality in the TRD thalamus. PMID- 17723271 TI - Media conditioned by retinal pigment epithelial cells suppress the canonical Wnt pathway. AB - Retinal pigment epithelial (RPE) cells play critical roles in the maintenance of visual function, partly by secreting various biologically active factors that modulate the intraocular environment. Recent studies suggest involvement of Wnt proteins secreted by RPE cells in the pathogenesis of photoreceptor degeneration. In the present study, we examined, via the luciferase assay, the effect of media conditioned by RPE cells (RPE-CM) on activity of the canonical Wnt pathway in vitro. We isolated primary RPE cells from Long-Evans rats at P6-P9. In culture, these cells formed a monolayer with polygonal cell morphology and demonstrated repigmentation at confluency and immunoreactivity for ZO-1, a marker for tight junctions. To evaluate the effect of RPE-CM on the canonical Wnt pathway, we replaced the culture media of COS-7 cells transfected with (Tcf)(7)LUC, a multimeric Tcf-responsive element luciferase reporter construct, with RPE-CM and measured luciferase activity with or without Wnt3a or SB216763, a specific GSK3 inhibitor. RPE-CM did not enhance basal or Wnt3a-induced (Tcf)(7)LUC activity; instead, this activity decreased by 60%. RPE-CM also reduced SB216763-induced (Tcf)(7)LUC activity by 65%, which suggests that the inhibitory effect of RPE-CM is probably due to intracellular crosstalk rather than extracellular antagonism. RPE cells may thus be able to modulate the intraocular environment by regulating the canonical Wnt pathway. PMID- 17723273 TI - Effects of methylphenidate in ADHD adults on target evaluation processing reflected by event-related potentials. AB - Attention deficit/hyperactivity disorder (ADHD) is a widely examined disease in childhood. There is evidence that the disease responds well to medication with methylphenidate (MPH). The effect of MPH in adults with ADHD is a question that is often raised, because many adults request such therapy today. As yet, there is a lack of studies on event-related potentials (ERPs) and MPH in ADHD adults. In the present study we examined 10 adults diagnosed with ADHD, with and without MPH medication (30 mg daily), by means of ERP in a visual Go/NoGo experiment to gain information about target evaluation processing in these patients and about the effects on these attentional processes during medication with MPH. Visually, there seem to be differences in the frontal electrodes for the N2 and in the parietal electrodes for the P300. But these differences do not achieve statistical significance. There are also no statistically relevant differences for the N1 or the slow wave. MPH does not seem to have an effect on target evaluation processing, when comparing the ERPs of non-medicated and medicated ADHD adults. Especially the P3 does not appear to be modulated by medication with MPH in these ADHD adults, in contrast to findings in ADHD children. PMID- 17723274 TI - Decreased gene expression of neuropeptide Y and its receptors in hippocampal regions during ethanol withdrawal in rats. AB - Ethanol withdrawal is associated with neuronal hyperexcitability and increased hippocampal glutamate release. Neuropeptide Y (NPY) appears to play an important role in regulation of hippocampal neuronal excitability by inhibiting glutamate release. Expression of NPY and its receptors Y1, Y2, and Y5 was studied in hippocampal areas of rats during ethanol withdrawal after repeated intragastric ethanol administration for 2 or 4 days using in situ hybridization. Withdrawal was associated with decreased hippocampal expression of NPY and each of its receptors, particularly Y2, after 2 and/or 4 days of ethanol compared to control rats. These data suggest that the hippocampal NPY system is downregulated during ethanol withdrawal and these neuroadaptational changes could play a role in mediating withdrawal hyperexcitability. PMID- 17723275 TI - Coordination of pointing and stepping: do postural phenomena result from the juxtaposition of the dynamics of each task? AB - We questioned whether postural phenomena associated with the coordination of pointing and stepping resulted from the sole juxtaposition of the dynamics of each task during the overlapping time period ("juxtaposition hypothesis"). Nine subjects were involved in three experimental conditions: (1) "isolated stepping" (the stepping was performed alone), (2) "isolated pointing" (the pointing was performed alone), and (3) an "experimental sequence" (pointing and stepping were coordinated). Acceleration of centre of gravity (x''G) and displacement of centre of foot pressure (xP) were recorded using a force plate. Pointing acceleration was recorded using a wrist-strapped mono-axial accelerometer. The dynamics of a "theoretical sequence" were calculated by the linear summation of x''G and xP traces recorded in conditions (1) and (2). The juxtaposition hypothesis was tested by between-condition comparison of x''G and xP during the anticipatory postural adjustments of stepping, i.e., at time intervals when pointing was expected to most significantly influence stepping. Results showed that x''G and xP were higher (p<0.001 and 0.01, respectively) in the experimental than in the theoretical sequence. Also, when compared to isolated stepping, the experimental sequence was performed with a higher x''G (p<0.01) while xP remained unchanged (p>0.05). Altogether, our results suggest that the postural dynamics of pointing and stepping are not simply juxtaposed when both tasks are coordinated in a motor sequence. Conversely, the biomechanical consequences of the focal movement (pointing) on the mobility task (stepping) may be anticipated and integrated in the motor planning of quick stepping. PMID- 17723276 TI - Multiphoton microscope imaging: the behavior of neural progenitor cells in the rostral migratory stream. AB - Neural progenitor cells (NPCs) in the subventricular zone (SVZ) travel a long distance along the rostral migratory stream (RMS) to give rise to interneurons in the olfactory bulb (OB). Using the multiphoton microscope and time-lapse recording techniques we here report the behavior of NPCs in the RMS under both intact and ischemic conditions in living brain slices. The NPCs were visualized in 3-week-old transgenic mice that carry the reporter gene, green fluorescent protein (GFP), driven by the nestin promoter. Cortical brain ischemia was induced by permanent occlusion of the right common carotid artery and the middle cerebral artery. We observed that the RMS contained two populations of NPCs: nonmigrating cells (bridge cells) and migrating cells. Bridge cells enabled migrating cells to travel and also produced new cells in the RMS. The direction of NPC migration in the RMS was bidirectional in both intact and ischemic conditions. Cortical ischemia impeded NPC travel in the RMS next to the lesion area during the early period of ischemia. Cell-cell contact was a prominent feature affecting NPC translocation and migratory direction. These data suggest that behavior and function of nestin-positive NPCs in the RMS are variable. Cell-cell contacts and microenvironmental changes influence NPC behavior in the RMS. This study may provide insights to help in understanding NPC biology. PMID- 17723277 TI - Expression of the cell surface markers mAb 2F7 and PSA-NCAM in the embryonic rat brain. AB - Cell surface markers of neuronal precursor cells are of interest since they allow the isolation of these cells from mixed populations of cells. The monoclonal antibody (mAb) 2F7, a cell surface marker, has been shown to label neuronal precursors and post-mitotic neurones in the embryonic rat spinal cord and cortex. Little is known about the expression of the epitope recognised by mAb 2F7 in other regions of the developing brain. The present study found expression of this epitope in the embryonic rat cortex, ventral mesencephalon (VM) and striatum at times at which neurogenesis is known to occur in these regions. The expression profile of mAb 2F7 was similar to that of the polysialylated form of the neural adhesion molecule (PSA-NCAM), a commonly used marker of neuronal precursor cells. The percentage of mAb 2F7-positive cells incorporating bromodeoxyuridine (BrdU) was found to be comparable to that of PSA-NCAM-positive cells in primary cell cultures of embryonic rat cortex, VM and striatum. These data demonstrate that mAb 2F7 can be used as a cell surface marker for neuronal precursor cells in several regions of the embryonic rat brain. PMID- 17723278 TI - Application of fractal analysis to neuronal dendritic arborisation patterns of the monkey dentate nucleus. AB - The deep nuclei of the cerebellar cortex have not yet received adequate exploratory attention. An exception is represented by the pioneering work of Chan Palay, published in 1977, on the dentate nucleus morphology. She has classified each individual cell in the dentatus of the monkey into one of six types. Although fractal analysis is presently the most prominent quantitative method for morphometric neuronal studies, no article referring to applications of this method to the analysis of cell types of the dentate nucleus has so far been published. In the present study we apply fractal analysis to this unsolved problem and calculate the fractal dimension for each dendritic arbour of a neuron. We will hereby prove that by application of fractal analysis to the dendritic arbours of these cells whilst ignoring other neuronal attributes allows for clear discrimination of only three cell types. PMID- 17723279 TI - Construct validity of a multidimensional electronic pain diary for adolescents with arthritis. AB - The aim of this study was to evaluate the construct validity and feasibility of a multidimensional electronic pain diary (e-Ouch(c)) in adolescents with juvenile idiopathic arthritis (JIA). Two descriptive studies with repeated measures were conducted between January and December 2005. Participants were drawn from a large metropolitan rheumatology clinic in a university affiliated pediatric tertiary care centre. In Study 1, 76 adolescents with active arthritis recorded their pain three times a day for 2weeks using the e-Ouch(c). In Study 2, 36 adolescents recorded their pain three times a day for 1week before and 2weeks after joint injections. Adolescents in both studies completed multiple measures to determine the construct validity and feasibility of the e-Ouch(c). Adolescents reported mild levels of pain intensity, unpleasantness, and interference as well as stiffness, and mild to moderate levels of fatigue. e-Ouch(c) average weekly pain unpleasantness and interference scores were higher in adolescents with higher pain intensity scores. Correlations between average weekly pain ratings on the e Ouch(c) and scores from: (a) recalled least, average and worst weekly pain, (b) health-related quality of life and pain coping, and (c) disease activity were as predicted. Pain ratings were significantly lower following joint injections with effect sizes in the low to moderate and moderate to high ranges at the first and second week post-injection, respectively. These findings provide evidence of the construct validity and feasibility of the e-Ouch(c) electronic diary in adolescents with JIA. Use of real-time data capture approaches should be considered in future studies of chronic arthritis. PMID- 17723280 TI - Molecular detection of bovine and porcine Torque teno virus in plasma and feces. AB - Torque teno virus (TTV) is frequently detected in humans, livestock and some companion animals. Very little is known about presence of TTV in Canadian livestock and the goal of this study was to evaluate the presence of TTV in swine and cattle using molecular tools. TTV DNA was detected and confirmed by sequencing in the plasma of 90.5% and in the feces of 60.3% of the animals tested in a single swine herd as well as 80.9% and 1.1% in the plasma of individuals from general Quebec swine and cattle populations, respectively. The impact of the TTV presence in livestock population for the agri-food chain should be further investigated. PMID- 17723281 TI - Comparison between ultrasonographic and caliper measurements of testicular volume in the dog. AB - The aim of this study was to compare the accuracy of two methods used to clinically estimate testicular volume in the dog. Caliper and ultrasonographic measurements of testicular dimensions (length, width and height) of both testes were performed on 21 adult Beagles. Either measurement was taken in vivo over the scrotal skin and again in vitro after castration, excluding or including, when possible, the epididymis. In a sub-sample of 14 testes of 7 randomly selected dogs, the testicular volume was calculated by the formula of an ellipsoid: length (l)xwidth (w)xheight (h)x0.5236, and the empiric formula of Lambert: (l)x(w)x(h)x0.71. The calculated volumes were then compared to the actual ones, which were estimated by water displacement. For each measurement method, the formula that estimated more accurately the true testicular volume was, subsequently, applied to the calculation of the testicular volume of the remaining testes. The formula of ellipsoid estimated testicular volume more accurately when in vivo and in vitro caliper measurements and in vitro ultrasound measurements were performed. The formula of Lambert estimated testicular volume more accurately when in vivo ultrasound measurements were performed. The volumes calculated from the measurements of calipers over the scrotal skin overestimated true volumes, on average, by 69+/-27% (concordance correlation coefficient r(ccc)=0.49). By contrast, those calculated from the ultrasonography measurements were more accurate, overestimating the true volumes by 17+/-24% (rccc=0.81). Therefore, ultrasonography when the formula of Lambert is used is more accurate than caliper methods for the estimation of testicular volume in clinical practice and should be the method of choice. PMID- 17723282 TI - Development of photocrosslinked polyacrylic acid hydrogel as an adhesive for dermatological patches: involvement of formulation factors in physical properties and pharmacological effects. AB - Photocrosslinked polyacrylic acid hydrogel is a promising candidate adhesive for dermatological patches. In this study, we investigated the effects of the composition and molecular weight of the polymer on the characteristics of the hydrogel. Several photocrosslinkable polymers with different photocrosslinkable moieties or molecular weights were prepared, and various physical properties were measured. Differences in photocrosslinkable modifications markedly affected the swelling behavior of the hydrogel. The molecular weight of the polymer had a significant effect on various physical properties, such as the viscosity of the polymer solution, gel formation, and the swelling behavior of the prepared hydrogels. The pharmacological effects of the hydrogel were also evaluated using carrageenan-induced edema in rats. Application of the hydrogels maintained the skin surface at a reduced temperature throughout the experimental period, and the cooling effect was accompanied by an anti-inflammatory response. Because we can freely control the physical properties of the hydrogel and anticipate the significant pharmacological effects, photocrosslinked polyacrylic acid hydrogel is an attractive candidate adhesive for dermatological patches. PMID- 17723283 TI - Uptake of inert microparticles in normal and immune deficient mice. AB - Intestinal microparticle uptake is important for drug delivery, environmental pollution and multiple organ dysfunction syndrome. This paper explores further whether uptake occurs at mucosa associated lymphoid tissue (MALT) via the microfold (M) cells of Peyer's patch domes or through villous epithelium. It does this by comparing the results of exposure of either severe combined immunodeficient (SCID) mice (lacking MALT) or normal BALBc mice, to oral gavage with 2 microm fluorescent latex microparticles. At 5 and 30 min after gavage, full circumference samples along the small intestine were processed for fluorescence microscopy and microparticle numbers were collected for surface and tissue sites. Uptake occurred in both BALBc and SCID mice within 5 min of particle administration and increased further in the following 25 min. In BALBc mice, almost all particles (96%) are in non-MALT sites in MALT circumference samples, with very few at the domes: uptake was also substantial in entirely villous samples. In SCID mice, particle numbers were only slightly lower than those of the BALBc mice, and occurred exclusively by the villous route. These findings confirm that the villous uptake route must be considered when assessing the extent of the dose delivered following pharmaceutical or toxicological oral exposure to microparticles. PMID- 17723284 TI - Acoustic-electric interactions in the guinea pig auditory nerve: simultaneous and forward masking of the electrically evoked compound action potential. AB - The study investigated the time course of the effects of acoustic and electric stimulation on the electrically evoked compound action potential (ECAP). Adult guinea pigs were used in acute experimental sessions. Bursts of acoustic noise and high-rate (5000 pulses/s) electric pulse trains were used as maskers. Biphasic electric pulses were used as probes. ECAPs were recorded from the auditory nerve trunk. Simultaneous masking of the ECAP with acoustic noise featured an onset effect and a decrease in the amount of masking to a steady state. It was characterized by a two-component exponential function. The amount of masking increased with masker level and decreased with probe level. Post stimulatory ECAP recovery often featured a non-monotonic time course, described by a three-component exponent. Electric maskers produced similar post-stimulatory effects in hearing and acutely deafened subjects. Acoustic stimulation affects the ECAP in a level- and time-dependent manner. Simultaneous masking follows a time course comparable to that of adaptation to an acoustic stimulus. Refractoriness, spontaneous activity, and adaptation are suggested to play a role in ECAP recovery. Post-stimulatory changes in synchrony, possibly due to recovery of spontaneous activity and an additional hair-cell independent mechanism, are hypothesized to contribute to the observed non-monotonicity of recovery. PMID- 17723286 TI - Effect of postnatal treadmill exercise on c-Fos expression in the hippocampus of rat pups born from the alcohol-intoxicated mothers. AB - Maternal alcohol-intoxication during pregnancy exerts detrimental effects on fetal development and is known to influence learning ability and memory capability by altering neuronal activity in the hippocampus. c-Fos expression represents neuronal activity and plays a crucial role in the brain development. Physical exercise is known to enhance neuronal plasticity and activity. In the present study, we investigated the influence of postnatal treadmill running on the c-Fos expression in the hippocampus of rat pups born from the alcohol intoxicated mothers. The results obtained show that maternal alcohol-intoxication suppressed c-Fos expression in the hippocampus of rat pups and that postnatal treadmill exercise enhanced c-Fos expression in the hippocampus of these rat pups. The present study suggests that exercise should be considered as a therapeutic means of countering the effects of maternal alcohol-intoxication, and that it may provide a useful strategy for enhancing the neuronal activity of children born from the mothers who abuse alcohol during pregnancy. PMID- 17723285 TI - A role for epigenetics in hearing: Establishment and maintenance of auditory specific gene expression patterns. AB - Epigenetics is a large and diverse field encompassing a number of different mechanisms essential to development, DNA stability and gene expression. DNA methylation and histone modifications work individually and in conjunction with each other leading to phenotypic changes. An overwhelming amount of evidence exists demonstrating the essential nature of epigenetics to human biology and pathology. This field has spawned a vast array of knowledge, techniques and pharmaceuticals designed to investigate and manipulate epigenetic phenomena. Despite its centricity to molecular biology, little work has been conducted examining how epigenetics affects hearing. In this review, we discuss both the basic tenets of epigenetics and highlight the most recent advances in this field. We discuss its importance to human development, genomic stability, gene expression, epigenetic modifying agents as well as briefly introduce the expansive field of cancer epigenetics. We then examine the evidence of a role for epigenetics in hearing related processes and hearing loss. The article concludes with a discussion of areas of epigenetic research that could be applied to hearing research. PMID- 17723287 TI - Identification and determination of four metabolites of mangiferin in rat urine. AB - Four metabolites of mangiferin were firstly isolated and identified from rat urine. The structures of the four metabolites were determined to be 1,3,7 trihydroxyxanthone (M-1), 1,3,6,7-tetrahydroxyxanthone (M-2), 1,3,6-trihydroxy-7 methoxyxanthone (M-3) and 1,7-dihydroxyxanthone (M-4), respectively. A simple and specific analytical method for determination of the four metabolites in rat urine was developed by high performance liquid chromatography (HPLC). Quercetin was employed as an internal standard. The correlation coefficients of the calibration curves were higher than 0.997, both intra- and inter-day precision of four metabolites were determined and their R.S.D. did not exceed 10%. The accuracy and linear range had been investigated in detail. The cumulative urinary excretions of the four metabolites were measured and the possible metabolic pathway of the metabolites was discussed. PMID- 17723288 TI - An in vitro embryotoxicity assay based on the disturbance of the differentiation of murine embryonic stem cells into endothelial cells. I: Establishment of the differentiation protocol. AB - The aim of the present study was to establish an experimental protocol to differentiate murine embryonic stem (ES) cells into endothelial cells in vitro. The spinner flask technique as well as the hanging drop method were used to generate so-called embryoid bodies (EBs). In order to find out the optimal differentiation environment, EBs were cultured under various experimental conditions for up to 14 days. The influence of basic fibroblast growth factor (bFGF) alone, vascular endothelial growth factor (VEGF) alone, bFGF and VEGF together and a cocktail consisting of bFGF, VEGF, interleukin-6 (IL-6) and erythropoietin (Epo) on the induction of differentiation of ES cells into endothelial cells was studied. Different concentrations of growth factors and times of treatment were applied. Endothelial cells were characterized by analyzing the expression of platelet-endothelial cell adhesion molecule (PECAM 1), the endothelial-specific vascular endothelial cadherin (VE-Cadherin), the angiopoietin receptor Tie-2, VEGF receptors 1 and 2 (Flt-1 and Flk-1, respectively) and the soluble form of Flt-1 (sFlt) at the mRNA level. PECAM-1 and VE-Cadherin were also studied at the protein level. The data clearly showed that EBs generated by the hanging drop method, followed by their transfer into suspension culture on day 3 of differentiation and their subsequent plating on day 5 is the best of the studied methods to differentiate ES cells into endothelial cells. Addition of VEGF alone or a cocktail consisting of VEGF, bFGF, IL-6 and Epo resulted in the strongest gene expression levels of the above mentioned endothelial cell markers in the differentiated ES cells. PMID- 17723289 TI - Young patients with focal seizures may have the primary motor area for the hand in the postcentral gyrus. AB - OBJECTIVE: We determined whether the primary motor hand area was most frequently located in the precentral gyrus in young patients with intractable focal seizures. METHODS: Sixty-five patients with focal seizures aged between 5 months and 20 years who underwent a two-stage epilepsy surgery using chronic subdural EEG monitoring were studied. Pairs of subdural electrodes were electrically stimulated, and the brain region with contralateral hand movement induced by the lowest-intense stimulus was defined as the primary motor hand area. RESULTS: Contralateral hand movement was induced without afterdischarges in 50 children but not in the remaining 15 children. The unpaired t-test revealed that failure to induce contralateral hand motor movement was associated with younger age of subjects. Among the 50 patients with a positive motor response, the primary motor hand area was confined to the precentral gyrus in 9 patients, confined to the postcentral gyrus in 24, and located in both the pre- and post-central gyri in the remaining 17. The McNemar's test revealed that the observed frequency of 24 patients showing the primary motor hand area confined to the postcentral gyrus was larger than chance frequency. Logistic regression analysis failed to demonstrate that the observation of the primary motor hand area confined to the postcentral gyrus was associated with the age, the presence of dysplastic lesion or the seizure onset involving the frontal lobe. CONCLUSION: Our study failed to support the traditionally-accepted notion that the primary motor hand area is most frequently located in the precentral gyrus but rather demonstrated that a substantial proportion of young patients had the primary motor hand area in the postcentral gyrus. PMID- 17723290 TI - A novel mutation of the FECH gene in a Chinese family with erythropoietic protoporphyria. PMID- 17723291 TI - CG400462, a new bacterial enoyl-acyl carrier protein reductase (FabI) inhibitor. AB - CG400462, a novel FabI inhibitor, has a potent antibacterial activity against staphylococci. The minimal inhibitory concentration at which 90% of bacterial strains tested were inhibited (MIC(90)) of CG400462 was 0.5 microg/mL against 238 strains of Staphylococcus aureus and 1.0 microg/mL against 51 strains of coagulase-negative staphylococci, irrespective of whether the strains were methicillin-susceptible or -resistant. CG400462 was also effective by subcutaneous administration against systemic infections in mice. In time-kill studies, CG400462 at concentrations of 1x, 2x and 4x MIC had a bacteriostatic activity over 24h. Genetic approaches have confirmed that the mode of action of CG400462 is via inhibition of FabI, which is involved in the biosynthesis of fatty acids in bacteria. Study of the resistance mechanism of S. aureus showed that CG400462-resistant mutants had an alteration in FabI of Met99-->Thr or Tyr147-->His. PMID- 17723292 TI - Porous silicon biosensor for detection of viruses. AB - There is a growing need for virus sensors with improved sensitivity and dynamic range, for applications including disease diagnosis, pharmaceutical research, agriculture and homeland security. We report here a new method for improving the sensitivity for detection of the bacteriophage virus MS2 using thin films of nanoporous silicon. Porous silicon is an easily fabricated material that has extremely high surface area to volume ratio, making it an ideal platform for surface based sensors. We have developed and evaluated two different methods for covalent bioconjugation of antibodies inside of porous silicon films, and we show that the pore penetration and binding efficiency depend on the wettability of the porous surface. The resulting films were used to selectively capture dye-labeled MS2 viruses from solution, and a viral concentration as low as 2 x 10(7) plaque forming units per mL (pfu/mL) was detectable by measuring the fluorescence from the exposed porous silicon film. The system exhibits sensitivity and dynamic range similar to the Luminex liquid array-based assay while outperforming protein micro-array methods. PMID- 17723293 TI - An integrated view of quantitative trait variation using tomato interspecific introgression lines. AB - Resolving natural phenotypic variation into genetic and molecular components is a major objective in biology. Over the past decade, tomato interspecific introgression lines (ILs), each carrying a single 'exotic' chromosome segment from a wild species, have exposed thousands of quantitative trait loci (QTL) affecting plant adaptation, morphology, yield, metabolism, and gene expression. QTL for fruit size and sugar composition were isolated by map-based cloning, while others were successfully implemented in marker-assisted breeding programs. More recently, integrating the multitude of IL-QTL into a single database has unraveled some unifying principles about the architecture of complex traits in plants. PMID- 17723294 TI - Revival of electron crystallography. AB - Since the structure determination of bacteriorhodopsin in 1990, much progress has been made in the further development and use of electron crystallography. In this review, we provide a concise overview of the new developments in electron crystallography concerning 2D crystallization, data collection and data processing. Based on electron crystallographic work on bacteriorhodopsin, the acetylcholine receptor and aquaporins, we highlight the unique advantages and future perspectives of electron crystallography for the structural study of membrane proteins. These advantages include the visualization of membrane proteins in their native environment without detergent-induced artifacts, the trapping of different states in a reaction pathway by time-resolved experiments, the study of non-specific protein-lipid interactions and the characterization of the charge state of individual residues in membrane proteins. PMID- 17723295 TI - Structure and mechanism of ABC transporter proteins. AB - ATP-binding cassette (ABC) transporters are ubiquitous membrane proteins that couple the transport of diverse substrates across cellular membranes to the hydrolysis of ATP. The crystal structures of four ABC transporters have recently been determined. They reveal similar arrangements of the conserved ATP hydrolyzing nucleotide-binding domains, but unrelated architectures of the transmembrane domains, with the notable exception of a common 'coupling helix' that is essential for transmitting conformational changes. The structures suggest a mechanism that rationalizes ATP-driven transport: While binding of ATP appears to trigger an outward-facing conformation, dissociation of the hydrolysis products may promote an inward-facing conformation. This basic scheme can, in principle, explain nutrient import by ABC importers and drug extrusion by ABC exporters. PMID- 17723296 TI - Synthesis and SAR of 2-aryl pyrido[2,3-d]pyrimidines as potent mGlu5 receptor antagonists. AB - A novel series of potent 2-aryl pyrido[2,3-d]pyrimidine mGlu5 receptor antagonists are described. The synthesis and pharmacological activities of these analogs are discussed. PMID- 17723298 TI - Conversion of the LXR-agonist TO-901317--from inverse to normal modulation of gamma-secretase by addition of a carboxylic acid and a lipophilic anchor. AB - TO-901317, a LXR agonist, is an inverse modulator of Alzheimer's disease associated gamma-secretase. We synthesized TO-901317 analogous compound but replaced the hexafluorocarbinol moiety by an oxyacetic acid functionality and hypothesized that the replacement would change the mode of action from an inverse modulation to normal modulation of gamma-secretase. As anticipated, acid 9 was found to be an effective modulator of gamma-secretase and displayed activity at low micromolar concentration. This significant modification can be applied to several inverse gamma-secretase modulators. Such modulators may preserve the cleavage of other gamma-secretase substrates such as Notch. PMID- 17723297 TI - Two new alkaloids and active anti-hepatitis B virus constituents from Hypserpa nitida. AB - Two new alkaloids, hypserpanines A and B (1, 11), together with eleven known compounds, phenolbetain (2), acutumine (3), acutumidine (4), dechloroacutumine (5), dauricumine (6), dauricumidine (7), pronuciferine (8), glaziovine (9), S reticuline (10), magnoflorine (12) and laurifoline(13), were isolated from Hypserpa nitida Miers. (Menispermaceae) and chemically elucidated through spectral analyses. All the isolated alkaloids were evaluated for their anti-HBV activities in vitro using the HBV transfected Hep G2.2.15 cell line. The most active compound, dauricumidine (7), exhibited an IC(50) value of 0.450 mM (SI=4.13) on hepatitis B virus (HBV) surface antigen (HBsAg) secretion of the Hep G2.2.15 cell line. PMID- 17723299 TI - Novel indanyl-substituted imidazo[1,2-a]pyridines as potent reversible inhibitors of the gastric H+/K+-ATPase. AB - A series of novel 8-indanylamino- and 8-indanyloxy-substituted imidazo[1,2 a]pyridines with reduced lipophilicity was synthesized from easily accessible starting compounds. The anti-secretory activity of these compounds has been assessed in a competitive binding assay against H(+)/K(+)-ATPase from hog gastric mucosa. Some of the compounds proved to be potent inhibitors of the gastric acid pump. PMID- 17723300 TI - Pyrrolidine-carboxamides and oxadiazoles as potent hNK1 antagonists. AB - The preparation and structure-activity-relationships of novel pyrrolidine carboxamides and oxadiazoles are described. Compounds in this series were found to be potent hNK(1) antagonists in vitro and efficacious in vivo with minimal interactions with P(450) liver enzymes. Oxadiazole analog 22 was determined to have excellent hNK(1) binding affinity, functional activity, and a good PD response in vivo. PMID- 17723301 TI - 1,2,4-benzothiadiazine linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates: synthesis, DNA-binding affinity and cytotoxicity. AB - Benzothiadiazine-pyrrolobenzodiazepine conjugates linked through different alkane spacers have been prepared. These new classes of hybrid molecules exhibit cytotoxicity against many cancer cell lines. Their DNA thermal denaturation studies have been carried out and one of the compounds (4b) elevates the DNA helix melting temperature of the CT-DNA by 6.7 degrees C after incubation for 36 h. PMID- 17723302 TI - Current status of the taxanes as adjuvant therapy for breast cancer. AB - Adjuvant chemotherapy for breast cancer reduces the risks of recurrence and death in many subsets of patients. The quest for better regimens, defined as both more effective and less toxic has led to numerous clinical trials testing the taxanes in the adjuvant setting. These trials are generally positive but do not clearly identify a single best or ideal regimen for all patients. This paper reviews the available data in this area of clinical research. PMID- 17723303 TI - Two simple methods for determining gait events during treadmill and overground walking using kinematic data. AB - The determination of gait events such as heel strike and toe-off provide the basis for defining stance and swing phases of gait cycles. Two algorithms for determining event times for treadmill and overground walking based solely on kinematic data are presented. Kinematic data from treadmill walking trials lasting 20-45s were collected from three subject populations (healthy young, n=7; multiple sclerosis, n=7; stroke, n=4). Overground walking trials consisted of approximately eight successful passes over two force plates for a healthy subject population (n=5). Time of heel strike and toe-off were determined using the two new computational techniques and compared to events detected using vertical ground reaction force (GRF) as a gold standard. The two algorithms determined 94% of the treadmill events from healthy subjects within one frame (0.0167s) of the GRF events. In the impaired populations, 89% of treadmill events were within two frames (0.0334s) of the GRF events. For overground trials, 98% of events were within two frames. Automatic event detection from the two kinematic-based algorithms will aid researchers by accurately determining gait events during the analysis of treadmill and overground walking. PMID- 17723304 TI - A novel series of parenteral cephalosporins exhibiting potent activities against Pseudomonas aeruginosa and other Gram-negative pathogens: synthesis and structure activity relationships. AB - A series of 7beta-[2-(2-aminothiazol-4-yl)-2-(Z) (carboxymethoxyimino)acetamido]cephalosporins bearing a 1-(substituted)-1H pyrrolo[3,2-b]pyridinium group at C-3' position was synthesized and their in vitro antibacterial activities against Pseudomonas aeruginosa and other Gram negative pathogens were evaluated. Among the cephalosporins prepared, 7beta-[2-(2 amino-5-chlorothiazol-4yl)-2(Z)-((S)-1 carboxyethoxyimino)acetamido]cephalosporins (42d) showed potent antibacterial activities against P. aeruginosa and other Gram-negative pathogens including the strains which produce class C beta-lactamase and extended spectrum beta-lactamase (ESBL). These results imply that both the Cl atom on the C-7 aminothiazole moiety and the alpha-substituent at the iminoether moiety are essential for the stability against beta-lactamase and the potent activity against Gram-negative bacteria including P. aeruginosa. PMID- 17723306 TI - Synthesis and antidiabetic activity of 2,5-disubstituted-3-imidazol-2-yl pyrrolo[2,3-b]pyridines and thieno[2,3-b]pyridines. AB - In the present investigation, two series of 2,5-disubstituted-3-imidazol-2-yl pyrrolo[2,3-b]pyridines (2a-l) and thieno[2,3-b]pyridines (3a-l) were designed as analogs of BL 11282 (1). The in vitro glucose dependent insulinotropic activity of all the test compounds was evaluated using RIN5F cell based assay and all the test compounds showed glucose and concentration dependent insulin secretion. The in vivo antidiabetic activities of most potent compounds from each series (2c and 3c) were assessed in C57BL/6J mice. Compounds 2c and 3c showed dose dependent insulin secretion and significant glucose reduction in vivo. In general, compounds 2c and 3c were found to be equipotent at all the three different doses selected and with respect to BL 11282, both the test compounds were found to be more potent, at all the time points. PMID- 17723305 TI - Inhibition of the Mycobacterium tuberculosis enoyl acyl carrier protein reductase InhA by arylamides. AB - InhA, the enoyl acyl carrier protein reductase (ENR) from Mycobacterium tuberculosis, is one of the key enzymes involved in the type II fatty acid biosynthesis pathway of M. tuberculosis. We report here the discovery, through high-throughput screening, of a series of arylamides as a novel class of potent InhA inhibitors. These direct InhA inhibitors require no mycobacterial enzymatic activation and thus circumvent the resistance mechanism to antitubercular prodrugs such as INH and ETA that is most commonly observed in drug-resistant clinical isolates. The crystal structure of InhA complexed with one representative inhibitor reveals the binding mode of the inhibitor within the InhA active site. Further optimization through a microtiter synthesis strategy followed by in situ activity screening led to the discovery of a potent InhA inhibitor with in vitro IC(50)=90 nM, representing a 34-fold potency improvement over the lead compound. PMID- 17723308 TI - Production and purification of the bacterial autolysin N-acetylmuramoyl-L-alanine amidase B from Pseudomonas aeruginosa. AB - The bacterial cell wall heteropolymer peptidoglycan is not a static structure as it is constantly being made and recycled throughout the bacterium's life cycle. This turnover of peptidoglycan is a highly coordinated event involving a complement of autolytic enzymes that include those with specificity for either the carbohydrate or the peptide linkages of peptidoglycan. One major class of these autolysins are the N-acetylmuramoyl-L-alanine amidases which cleave the amide linkage between the stem peptides and the lactyl moiety of muramoyl residues. They are required in the periplasm for cell separation during division and in both the periplasm and cytoplasm to trim soluble released PG fragments during turnover for recycling. The gene encoding N-acetylmuramoyl-L-alanine amidase B in Pseudomonas aeruginosa was cloned and over-expressed in Escherichia coli. The recombinant protein with a C-terminal His-tag was purified to apparent homogeneity by a combination of affinity and cation-exchange chromatographies using Ni(2+)NTA-agarose and Source S, respectively. Four separate assays involving zymography, light scattering, HPLC and MALDI-TOF mass spectrometry were used to confirm the activity of the protein as an N-acetylmuramoyl-L-alanine amidase. PMID- 17723307 TI - Profiling of membrane protein variants in a baculovirus system by coupling cell surface detection with small-scale parallel expression. AB - Production of structure-grade mammalian membrane proteins in substantial quantities has been hindered by a lack of methods for effectively profiling multiple constructs expression in higher eukaryotic systems such as insect or mammalian cells. To address this problem, a specialized small-scale eukaryotic expression platform by Thomson Instrument Company (Vertiga-IM) was developed and used in tandem with a Guava EasyCyte microcapillary 96-well cytometer to monitor cell density and health and evaluate membrane protein expression. Two proof of concept experiments were conducted using the human beta(2)-adrenergic receptor (beta(2)AR) and the gap junction protein connexin26 (Cx26) in a baculovirus expression system. First, cell surface expression was used to assess the expression levels of 14 beta(2)AR truncation variants expressed using the Vertiga IM shaker. Three of these variants were then compared to wild-type beta(2)AR using three metrics: cell surface expression, saturation ligand binding and protein immunoblot analysis of dodecylmaltoside extracted material. Second, a series of systematic Cx26 truncation variants were evaluated for expression by protein immunoblot analysis. The cumulative results for these two systems show that the Vertiga-IM instrument can be used effectively in the parallel insect cell microexpression of membrane protein variants, and that the expression of cell surface molecules as monitored with the Guava EasyCyte instrument can be used to rapidly assess the production of properly folded proteins in the baculovirus expression system. This approach expedites the in vitro evaluation of a large number of mammalian membrane protein variants. PMID- 17723310 TI - Analysis of differential gene expression in the generalist entomopathogenic fungus Beauveria bassiana (Bals.) Vuillemin grown on different insect cuticular extracts and synthetic medium through cDNA-AFLPs. AB - The entomopathogen Beauveria bassiana has an extremely diverse insect host range in addition to a saprophytic phase. The molecular basis for this plasticity was investigated by a comparative analysis of gene expression patterns through cDNA AFLPs of a B. bassiana isolate grown on cuticular extracts of insects of diverse orders as well as synthetic medium. For some of the fragments, expression patterns were verified by Q-RT-PCR. Among the differentially expressed genes two proteases were identified, which are known to be directly involved in the process of pathogenesis in entomopathogenic fungi. However, the majority of the transcript derived fragments identified have a rather indirect function in fungal pathogenesis, as they are involved in the regulation of gene expression, signal transduction, cytoskeleton formation or secretion. In general, the gene expression profile of the fungal isolate on cuticular extracts of diverse insects was pretty similar. This sheds light on the putative generalist nature of B. bassiana with its ability to penetrate many different insect cuticles possibly due to a rather stereotype gene expression program. PMID- 17723309 TI - A freeze substitution fixation-based gold enlarging technique for EM studies of endocytosed Nanogold-labeled molecules. AB - We have developed methods to locate individual ligands that can be used for electron microscopy studies of dynamic events during endocytosis and subsequent intracellular trafficking. The methods are based on enlargement of 1.4 nm Nanogold attached to an endocytosed ligand. Nanogold, a small label that does not induce misdirection of ligand-receptor complexes, is ideal for labeling ligands endocytosed by live cells, but is too small to be routinely located in cells by electron microscopy. Traditional pre-embedding enhancement protocols to enlarge Nanogold are not compatible with high pressure freezing/freeze substitution fixation (HPF/FSF), the most accurate method to preserve ultrastructure and dynamic events during trafficking. We have developed an improved enhancement procedure for chemically fixed samples that reduced auto-nucleation, and a new pre-embedding gold enlarging technique for HPF/FSF samples that preserved contrast and ultrastructure and can be used for high-resolution tomography. We evaluated our methods using labeled Fc as a ligand for the neonatal Fc receptor. Attachment of Nanogold to Fc did not interfere with receptor binding or uptake, and gold-labeled Fc could be specifically enlarged to allow identification in 2D projections and in tomograms. These methods should be broadly applicable to many endocytosis and transcytosis studies. PMID- 17723312 TI - Affective pain modulation in fibromyalgia, somatoform pain disorder, back pain, and healthy controls. AB - Previous research suggested that patients with fibromyalgia (FM) experience a higher pain intensity (clinical pain) than do patients with musculoskeletal pain after negative emotional priming compared to positive priming. To further examine affective pain modulation in FM, we applied an experimental pain induction to compare 30 patients with FM with 30 healthy (pain-free) participants (HC), and 30 patients with back pain (BP). For another group of 30 patients with somatoform pain disorder (SF), we predicted the same pain modulation as for FM. As primes we presented positive, neutral, negative, and pain-related pictures and assessed pain intensity in response to a fixed pressure weight. Overall, picture valence modulated pain intensities (in the order of pain-related > negative pictures > neutral), but the pain intensities between neutral and positive pictures did not differ significantly. SF reported significantly higher pain intensities than did BP and HC; FM were in between, but did not differ significantly from the three other groups. There was no interaction of priming and group. Affective modulation of pain was not specifically altered in FM and SF, but SF were more sensitive to pressure pain than BP and HC. PMID- 17723311 TI - Nitric oxide production in mouse and rat macrophages: a rapid and efficient assay for screening of drugs immunostimulatory effects in human cells. AB - Activation of inducible nitric oxide (NO) synthase (iNOS) and resulting high output NO release is known to depend on the action of cytokines. We investigated in vitro production of NO by resident peritoneal macrophages from mice and rats, and secretion of cytokines by these cells as well as by human peripheral blood mononuclear cells (PBMC). The cells were cultured in the presence of a selected group of acyclic nucleoside phosphonates that have previously been shown to possess immunobiological potential. Several of the compounds enhanced production of NO in animal macrophages. This activity was associated with stimulatory effects on secretion of cytokines such as TNF-alpha in all mouse and rat macrophages and human PBMC, and IL-10 in mouse and human cells. Statistically highly significant correlation between the range of NO biosynthesis in rodent cells and extent of cytokine stimulation in human PBMC has been observed. It is suggested that the NO assay may be regarded as an efficient, economical and relatively reliable tool in primary screening for intrinsic immunostimulatory activity of compounds in human cell system, at least from the point of view of cytokine secretion. PMID- 17723313 TI - NMR data processing using iterative thresholding and minimum l(1)-norm reconstruction. AB - Iterative thresholding algorithms have a long history of application to signal processing. Although they are intuitive and easy to implement, their development was heuristic and mainly ad hoc. Using a special form of the thresholding operation, called soft thresholding, we show that the fixed point of iterative thresholding is equivalent to minimum l(1)-norm reconstruction. We illustrate the method for spectrum analysis of a time series. This result helps to explain the success of these methods and illuminates connections with maximum entropy and minimum area methods, while also showing that there are more efficient routes to the same result. The power of the l(1)-norm and related functionals as regularizers of solutions to underdetermined systems will likely find numerous useful applications in NMR. PMID- 17723314 TI - MR diffusion - "diffraction" phenomenon in multi-pulse-field-gradient experiments. AB - Using pulsed-field-gradient (PFG) experiments, the sizes of the pores in ordered porous media can be estimated from the "diffraction" pattern that the signal attenuation curves exhibit. A different diffraction pattern is observed when the experiment is extended to a larger number (N) of diffusion gradient pulse pairs. Simulations to calculate signal values from arbitrary gradient waveforms are performed for diffusion in restricted geometries using a matrix operator formalism. The simulations suggest that the differences in the characteristics of the attenuation curves are expected to make it possible to measure smaller pore sizes, to improve the accuracy of pore size measurements and potentially to distinguish different pore shapes using the N-PFG technique. Moreover, when an even number of PFG pairs is used, it is possible to observe the diffraction pattern at shorter diffusion times and measure an approximation to the average pore size even when the sample contains pores with a broad distribution of sizes. PMID- 17723315 TI - Development of a clinical assay for detection of GAA mutations and characterization of the GAA mutation spectrum in a Canadian cohort of individuals with glycogen storage disease, type II. AB - Glycogen storage disease, type II (GSDII; Pompe disease; acid maltase deficiency) is an autosomal recessive disease caused by mutations of the GAA gene that lead to deficient acid alpha-glucosidase enzyme activity and accumulation of lysosomal glycogen. Although measurement of acid alpha-glucosidase enzyme activity in fibroblasts remains the gold standard for the diagnosis of GSDII, analysis of the GAA gene allows confirmation of clinical or biochemical diagnoses and permits predictive and prenatal testing of individuals at risk of developing GSDII. We have developed a clinical molecular test for the detection of GAA mutations based on cycle sequencing of the complete coding region. GAA exons 2-20 are amplified in six independent PCR using intronic primers. The resulting products were purified and sequenced. Preliminary studies using this protocol were conducted with DNA from 21 GSDII-affected individuals from five centers across Canada. In total, 41 of 42 mutations were detected (96.7% detection rate). Mutations spanned intron 1 through exon 19 and included nine novel mutations. Haplotype analysis of recurrent mutations further suggested that three of these mutations are likely to have occurred independently at least twice. Additionally, we report the identification of the c.-32-13T>G GAA mutation in an individual with infantile variant GSDII, despite reports of this mutation being associated almost exclusively with late-onset forms of the disease. The development of a clinical molecular test provides an important tool for the management and counseling of families and individuals with GSDII, and has provided useful information about the GAA mutation spectrum in Canada. PMID- 17723316 TI - Pyomyositis associated with hematological malignancy: case report and review of the literature. AB - Pyomyositis occurs most commonly in patients with various immunosuppressive diseases. However, the association of pyomyositis with an underlying hematological malignancy has not been reviewed. We present herein a relevant case and also review the available literature regarding the association of non tropical pyomyositis and hematological malignancies. The case patient, a 46-year old female, had non-tropical pyomyositis of the iliopsoas and obturator muscles due to Staphylococcus aureus and underlying Hodgkin's disease. Forty-four patients with pyomyositis and an associated hematological malignant disease have been reported in the literature. The most common types of hematological oncology diseases found were acute lymphocytic leukemia (present in 11/44 patients (25%)) and multiple myeloma (7/44 patients (15.9%)). Staphylococcus aureus was the most common cause of pyomyositis (26 out of 44 patients (59.1%)). The muscles of the thigh were most commonly affected (18/44 patients (40.9%)). Medical therapy with antibiotics and surgical drainage were employed in 25/44 (56.8%) of the patients. Thirty out of 44 (68.2%) of the patients had a successful outcome. Death occurred in 5/44 (11.4%) patients. In cases of pyomyositis, the physician should consider an underlying hematological malignancy. PMID- 17723317 TI - New trends in telescopic remote Raman spectroscopic instrumentation. AB - Raman spectroscopy is a powerful analytical technique in many areas of research for several reasons. These include the sensitivity to small structural changes, non-invasive sampling capability, minimal sample preparation, narrow line widths of Raman lines, and high spatial resolution in the case of micro-Raman spectroscopy. Advancements in lasers, spectrographs and holographic optical components have made Raman spectroscopy an effective tool for analyzing natural and synthetic materials. These advances have led to the development of both in situ Raman spectroscopy and telescopic remote Raman spectroscopy for a lander or rover for planetary exploration. A telescopic Raman spectroscopic system capable of measuring Raman spectra of minerals, inorganic and organic chemicals, and biogenic materials to radial distances in the range 10-100 m has been developed. In this work, the author reviews the current status of telescopic remote Raman spectroscopic instrumentation and examines new trends in the field of remote Raman spectroscopy and its combination with time-resolved remote laser-induced native fluorescence (LINF) and laser-induced breakdown spectroscopy (LIBS), and their applications in earth and planetary science. PMID- 17723318 TI - Combined remote LIBS and Raman spectroscopy at 8.6m of sulfur-containing minerals, and minerals coated with hematite or covered with basaltic dust. AB - Combined remote laser-induced breakdown spectroscopy (LIBS) and Raman spectroscopy investigations at a distance of 8.6m have been carried out in air and under a simulated Martian atmosphere of 933Pa (7Torr) CO(2) on calcite (CaCO(3)), gypsum (CaSO(4).2H(2)O), and elemental sulfur (S), and LIBS investigations on chalcopyrite (CuFeS(2)) and pyrite (FeS(2)). Both Raman and LIBS techniques have also been used sequentially in air on hematite-coated calcite crystals and on a sample of anhydrite covered with basaltic dust. These experiments demonstrate that by using a frequency-doubled Nd:YAG pulsed laser co radiating 1064 nm and 532 nm laser beams with a 5x beam expander, it is possible to measure simultaneously both the Raman and LIBS spectra of calcite, gypsum and elemental sulfur by adjusting the laser power electronically. The spectra of calcite, gypsum, and elemental sulfur contain fingerprint Raman lines; however, it was not possible to measure the remote Raman spectra of pyrite and chalcopyrite because of low intensities of Raman lines. In the cases of CuFeS(2), FeS(2), and elemental sulfur, S atomic emission lines in the LIBS spectra were detected only in 7Torr of CO(2) pressure and not in air. No S atomic emission lines were detected for gypsum in air or in CO(2). In the case of coated/dusted minerals, it was possible to remove the coating or dust with the focused LIBS laser and measure the Raman spectra of subsurface minerals with a 532 nm laser excitation. The complementary nature of these two techniques is highlighted and discussed. PMID- 17723319 TI - Differential 2-D protein gel electrophoresis analysis of Legionella pneumophila wild type and Tat secretion mutants. AB - The twin-arginine translocation (Tat) pathway is a secretory pathway for translocation of folded proteins with two arginines in their signal peptide across the cytoplasmic membrane. Recently, we showed the presence of the Tat secretion pathway in Legionella pneumophila Philadelphia-1 and its role in intracellular replication and biofilm formation. To analyse the importance of the Tat pathway in protein export and its role in L. pneumophila virulence, a comparative 2-D protein gel electrophoresis analysis was performed on supernatants of the wild type and two Tat secretion mutants in order to identify possible Tat substrates. Twenty proteins were identified as differential proteins, eight of which were present in a lower quantity in the supernatant of the tat mutants. Among these, one protein with a typical twin-arginine motif in its signal peptide was identified as the 3',5'-cyclic nucleotide phosphodiesterase. Two other proteins that resulted as differential proteins from this study were flagellin and LvrE, which were studied in more detail and their Tat-dependence was further confirmed with specific antibodies. LvrE was shown to play a role in intracellular growth in differentiated U937 cells. PMID- 17723320 TI - Cardiac papillary fibroelastoma of the mitral chorda. AB - We describe a case of cardiac papillary fibroelastoma in a 33-year-old man. The diagnosis was established by echocardiography. Computerised tomographic angiography gave no evidence of coronary stenosis, but illustrated a radiopaque filling defect in the left ventricle. The papillary fibroelastoma was removed together with the involved chorda, and an artificial chord was implanted under cardiopulmonary bypass. Histological study confirmed the diagnosis of papillary fibroelastoma. Due to the potentials of cerebral and coronary embolisation, surgical management to the patients with a papillary fibroelastoma is highly recommended. PMID- 17723321 TI - Indirect determination of pyruvic acid by capillary electrophoresis with amperometric detection. AB - A method of indirectly measuring pyruvic acid (PA) by capillary electrophoresis with amperometric detection is proposed for the first time. It is based on the oximation reaction between PA and hydroxylamine (NH(2)OH), and the quantification of PA was performed by direct and sensitive amperometric detection of excessive NH(2)OH after the oximation reaction. This method displayed a good sensitivity, and the detection limits of NH(2)OH and PA are 1.76 x 10(-7) and 3.88 x 10( 7)mol/L, respectively at S/N=3. The linear relationship between the peak current and PA concentration is exhibited over the range from 4 x 10(-6) to 1 x 10( 4)mol/L. This method has been applied to determine PA in rat plasma with satisfactory results. PMID- 17723322 TI - Surgical therapy of perianal Crohn's disease. AB - The surgical management of perianal Crohn's disease is complex with a wide range of operations being described. The initial emergency treatment is to drain any source of underlying sepsis. A loose seton drainage or a defunctioning stoma can then be used as a 'bridge' to definitive treatment allowing both adequate assessment of the condition and preventing further sepsis. The likelihood of success of any surgical repair must be weighed against the risk of faecal incontinence. Improved results of a local surgical repair are seen with optimal surgical and medical management of perianal Crohn's disease. PMID- 17723323 TI - Perianal Crohn's disease: overview. PMID- 17723325 TI - Formation of osteoclast-like cells on HA and TCP ceramics. AB - An essential property of bone substitute materials is that they are integrated into the natural bone remodelling process, which involves the resorption by osteoclast cells and the formation by osteoblast cells. If monocyte cells adhere to a calcium phosphate surface (bone or bone substitute material), they can fuse together and form multinucleated osteoclast cells. In this study we show that osteoclast-like cells derived from a human leukoma monocytic lineage responded in a different way to tricalciumphosphate (TCP) than to hydroxyapatite (HA) ceramics. Both ceramics were degraded by resorbing cells; however, HA enhanced the formation of giant cells. The osteoclast-like cells on HA formed a more pronounced actin ring, and larger lacunas could be observed. TCP ceramics are medically used as bone substitute materials because of their high dissolution rate. On the other hand, highly soluble calcium phosphate ceramics like TCP seem to be inappropriate for osteoclast resorption because they produce a high calcium concentration in the osteoclast interface and in the environment. PMID- 17723324 TI - Familial prevalence among first-degree relatives of celiac disease in North India. AB - BACKGROUND AND OBJECTIVES: Prevalence of celiac disease is increased in first degree relatives with reported prevalence rates in the west between 2.8 and 10%. Paucity of similar data from Asia and the Indian subcontinent prompted us to determine the familial prevalence of celiac disease in first-degree relatives of patients diagnosed with this disorder in Northern India. METHODS: One hundred sixty-nine first-degree relatives (66 parents, 71 siblings and 32 children) of 53 probands were screened by using anti tissue transglutaminase antibodies. Duodenal biopsy was performed in all seropositive relatives and graded as per Marsh classification. Patients with both positive serology and biopsy suggestive of celiac disease were classified as typical celiac disease whereas those with only positive serology were classified as potential celiacs. RESULTS: The prevalence of celiac disease among first-degree relatives was 8.2% (14/169). The prevalence of celiac disease among siblings (15.6%) was much higher as compared to that in parents (3.5%) and offspring (3%). More than one family member was affected in 23% (12/53) of families. Of 14 new cases detected by targeted screening, 11 (78%) were overtly symptomatic with either chronic diarrhoea (8) or easy fatiguability (3). Growth retardation was seen in all six newly diagnosed children, three of whom (22%) were otherwise asymptomatic. Eight members detected to be seropositive had minimal changes on duodenal biopsy (Marsh I and II) suggesting that they have potential celiac disease. CONCLUSION: Familial prevalence of celiac disease in North India is similar to the data from the West. However unlike the situation in the West, the overwhelming majority of first-degree relatives in India are overtly symptomatic with majority having chronic diarrhoea. Since gluten restriction is a highly effective treatment modality, early detection of these patients would result in significant improvement in quality of life as manifested by cessation of diarrhoea and improvement in growth and lab parameters. Our data strongly supports the targeted screening of all first-degree relatives of celiac disease patients in north India. PMID- 17723327 TI - Recent analytical methodologies on equilibrium, kinetics, and dynamics at liquid/liquid interface. AB - The form of liquid/liquid interface is flexible and it cannot be fixed at a spatial position. Also the interface is prevented from any physical contact by the organic phase and aqueous phase. In addition, analytical methods operated in vacuo cannot be applied. These restrictions depressed the development of liquid/liquid interfacial chemistry. However, the modification of liquid/liquid interfacial form and original analytical methods have been invented interdependently. The present review classifies the forms of liquid/liquid interface first, and it arrays the related analytical methods with brief explanations. It dominantly deals with recent reports of analytical methodologies, which were published in 2001-2004, on equilibrium, kinetics, and dynamics of substances at liquid/liquid interface, but it also includes historically important studies. PMID- 17723328 TI - DNA-based bioanalytical microsystems for handheld device applications. AB - This article reviews and highlights the current development of DNA-based bioanalytical microsystems for point-of-care diagnostics and on-site monitoring of food and water. Recent progresses in the miniaturization of various biological processing steps for the sample preparation, DNA amplification (polymerase chain reaction), and product detection are delineated in detail. Product detection approaches utilizing "portable" detection signals and electrochemistry-based methods are emphasized in this work. The strategies and challenges for the integration of individual processing module on the same chip are discussed. PMID- 17723326 TI - Recent advances in analytical chemistry--a material approach. AB - Advancements of materials research have profound direct impacts on developments in analytical chemistry and may hold the key to improvement of existing or new techniques at present times and near future. Applications of materials in analytical chemistry are reviewed, with focus on sensors, separations and extraction techniques. This review aims to survey examples of interesting works carried out in the last five years over a broad spectrum of materials classified as hybrids, nanomaterials and biomolecular materials. PMID- 17723329 TI - Analytical applications of room-temperature ionic liquids: a review of recent efforts. AB - Room-temperature ionic liquids (RTILs) are solvents that may have great potential in chemical analysis. Recent surge in the number of publications/reports/books/monographs clearly indicate an increasing interest of scientific and engineering community toward these exciting and unique solvents. Consequently, a variety of analytical applications of RTILs have started to emerge. This review presents an account of some of the recent reports on RTILs in major subdisciplines of analytical chemistry. Specifically, recent literature representing the applications of RTILs in chromatography, extraction, electroanalytical chemistry, sensing, and spectrometry is reviewed. With a rapid growth in the number of publications on analytical applications of RTILs, it appears that in the near future these neoteric solvents are definitely going to be a permanent feature in analytical chemistry. PMID- 17723331 TI - Designing split reporter proteins for analytical tools. AB - A current focus of biological research is to quantify and image cellular processes in living cells and animals. To detect such cellular processes, genetically-encoded reporters have been extensively used. The most common reporters include firefly luciferase, renilla luciferase, green fluorescent protein (GFP) and its variants with various spectral properties. This review describes novel design of split-GFP and luciferase reporters based on protein splicing, and highlights some potential applications with the reporters to study protein-protein interactions, protein localization, intracellular protein dynamics, and protein activity in living cells and animals. PMID- 17723330 TI - Electrochemical non-enzymatic glucose sensors. AB - The electrochemical determination of glucose concentration without using enzyme is one of the dreams that many researchers have been trying to make come true. As new materials have been reported and more knowledge on detailed mechanism of glucose oxidation has been unveiled, the non-enzymatic glucose sensor keeps coming closer to practical applications. Recent reports strongly imply that this progress will be accelerated in 'nanoera'. This article reviews the history of unraveling the mechanism of direct electrochemical oxidation of glucose and making attempts to develop successful electrochemical glucose sensors. The electrochemical oxidation of glucose molecules involves complex processes of adsorption, electron transfer, and subsequent chemical rearrangement, which are combined with the surface reactions on the metal surfaces. The information about the direct oxidation of glucose on solid-state surfaces as well as new electrode materials will lead us to possible breakthroughs in designing the enzymeless glucose sensing devices that realize innovative and powerful detection. An example of those is to introduce nanoporous platinum as an electrode, on which glucose is oxidized electrochemically with remarkable sensitivity and selectivity. Better model of such glucose sensors is sought by summarizing and revisiting the previous reports on the electrochemistry of glucose itself and new electrode materials. PMID- 17723332 TI - Advanced analytical tools in proteomics. AB - Proteomics deals with the study of proteins, their structures, localizations, posttranslational modifications, functions and interactions with other proteins. The mapping of protein structure-function holds the key to a better understanding of cellular functions under both normal and disease states, which is critical for modern drug discovery. However, the study of human proteome presents scientists with a task much more daunting than the human genome project. In fact, the estimated >100,000 different proteins expressed from 30,000 to 40,000 human genes make it extremely challenging, if not impossible with existing protein analysis techniques, to map the entire cellular functions at the translational level. Consequently, there have been rapid advances in the techniques and methods capable of large-scale proteomic studies. Among them, the recently developed high throughput screening methods have enabled scientists to analyze proteins quickly and efficiently at an organism-wide scale. Herein, we overview some of these emerging tools for high-throughput protein analysis. In particular, we focus on recent advances in the bioassay development, which has provided sensitive and selective tools for high-throughput identification and characterizations of enzymes. Finally, the recently developed bioimaging techniques to visualize and quantify proteins in living cells are also discussed. PMID- 17723334 TI - Separations based on the mechanical forces of light. AB - A photon as a particle has an energy and a momentum. In a matter-photon interaction, the matter and photons may exchange their momenta observing the momentum conservation law. The consequence of the momentum transfer from a photon to a matter particle is a mechanical force exerted on the particle. Several separation methods based on this force of light are reviewed. Photophoresis separations for micron-sized particles and optical force chromatography for chemical-sized molecules are discussed. PMID- 17723333 TI - Polymeric microfluidic system for DNA analysis. AB - The application of micro total analysis system (microTAS) has grown exponentially in the past decade. DNA analysis is one of the primary applications of microTAS technology. This review mainly focuses on the recent development of the polymeric microfluidic devices for DNA analysis. After a brief introduction of material characteristics of polymers, the various microfabrication methods are presented. The most recent developments and trends in the area of DNA analysis are then explored. We focus on the rapidly developing fields of cell sorting, cell lysis, DNA extraction and purification, polymerase chain reaction (PCR), DNA separation and detection. Lastly, commercially available polymer-based microdevices are included. PMID- 17723335 TI - Separation of antidepressants by capillary electrophoresis with in-line solid phase extraction using a novel monolithic adsorbent. AB - The separation of three selective serotonin reuptake inhibitors (SSRIs) by capillary electrophoresis (CE) with fully integrated solid-phase extraction (SPE) is described. Polymeric monolithic SPE modules were prepared in situ within a fused silica capillary from either butyl methacrylate-co-ethylene dimethacrylate or 3-sulfopropyl methacrylate-co-butyl methacrylate-co-ethylene dimethacrylate. Using a 1cm SPE module placed at the inlet of the capillary, a mixture of sertraline, fluoxetine and fluvoxamine was extracted from aqueous solution by applying a simple pressure rinse. Under pressure-driven conditions, efficient elution was possible from both SPE materials investigated using 50mM phosphate buffer, pH 3.5 in acetonitrile (20/80, v/v). Two different strategies were investigated for the efficient elution and subsequent CE separation. Injection of an aqueous sample plug directly into the non-aqueous elution/separation buffer was found to be unsuitable with poor elution profiles observed in the electrodriven mode. Alternatively, a sample plug equivalent to several capillary volumes could be injected by pressure followed by filling the capillary with the non-aqueous elution/separation buffer from the outlet end using a combination of pressure and electrodriven flow. Using a neutral monolith, efficient elution/separation was not possible due to an unstable electroosmotic flow (EOF), however, by adding the ionisable monomer, 3-sulfopropyl methacrylate to the SPE module to increase and stabilise the EOF, it was possible to achieve efficient elution from the SPE module, followed by baseline separation by CE using a 200 mM acetate buffer, pH 3.5 in acetonitrile (10/90, v/v). With enrichment factors of over 500 achieved for each of the analytes this demonstrates the potential of in line SPE-CE for the sensitive analysis of these drugs. PMID- 17723336 TI - Measurement of ordered associate of protonated tetraphenylporphine formed at toluene/aqueous H2SO4 interface by attenuated total internal reflection spectroscopy with polarized light. AB - Attenuated total internal reflection (ATR) spectroscopy with an s- or p-polarized visible light was examined for some species of protonated 5,10,15,20 tetraphenylporphine (tpp) at toluene/aqueous H2SO4 (3-6 mol dm(-3)) interface. Tpp initially dissolved in the toluene phase was diprotonated at the interface to form monomeric H2tpp2+, the absorption peak of which was 438nm. At the same time, a long H2tpp2+ oligomer was formed, the absorption peak of which was 448 nm. The two interfacial species were transient. Just after their disappearance, a rod shaped H2tpp2+ associate was formed at the interface, the absorption peak of which was 417 and 478 nm. The former and latter wavelengths corresponded to H- and J-bands of the associate, respectively. Theoretical calculation of the strength of electric field of light at the interface allowed one to estimate the interfacial concentration of the three species with measured reflection absorbance (A(R)). The monomeric H2tpp2+ and its oligomer were at sub-monolayer levels, whereas the associate was at a multilayer level. Reflection absorption anisotropy (K(R)), which was calculated from A(R) with the s- and p-polarized lights, was adopted for the evaluation of out-of-plane orientation of the interfacial species for the first time. The K(R) value suggested that the rod shaped associate lay at the interface. PMID- 17723337 TI - Preconcentration and frontal electroelution of amino acids for in-line solid phase extraction-capillary electrophoresis. AB - A new frontal electroelution approach that can be used for the preconcentration of amino acids in in-line solid-phase extraction-capillary electrophoresis (SPE CE) has been developed. A single capillary was employed featuring a short monolithic SPE column created inside the capillary via photo-initiated, free radical polymerisation of 3-sulfopropyl methacrylate and butyl methacrylate monomers. A weak electrolyte of dilute H2SO4, pH 2.9, was found to promote adsorption of the amino acids onto the SPE column. Elution of the amino acids was achieved using a dual solvation/ion-exchange transient boundary mobilised via EOF by using a strong electrolyte containing 62.5mM ethylenediamine, pH 2.9 with H2SO4 and 40% (v/v) acetonitrile. Using these two electrolytes, tryptophan was adsorbed onto the SPE column in weak electrolyte and eluted via a frontal electroelution mechanism in the strong electrolyte. Injections up to 20 min, corresponding to over 14 column volumes (or 1400% of the capillary volume) of sample provided quantitative extraction of tryptophan from the weak electrolyte and were eluted without any loss in efficiency. This represents a practical increase of approximately 300-fold when compared to a typical hydrodynamic injection occupying 5% of the capillary volume. PMID- 17723339 TI - Use of vitamin B2 for fluorescence detection of thymidine-related single nucleotide polymorphisms. AB - In combination with abasic site (AP site)-containing DNAs, potential use of a biotic fluorescence compound, Vitamin B2 (riboflavin), is demonstrated for the fluorescence detection of the thymine (T)-related single-nucleotide polymorphisms. Our method is based on construction of the AP site in DNA duplexes, which allows small ligands to bind to target nucleotides accompanied by fluorescence signaling: an AP site-containing probe DNA is hybridized with a target DNA so as to place the AP site toward a target nucleobase, by which hydrophobic microenvironments are provided for ligands to recognize target nucleotides through stacking and hydrogen-bonding interactions. In 10 mM sodium cacodylate buffer solutions (pH 7.0) containing 100 mM NaCl and 1.0 mM EDTA, Vitamin B2 is found to selectively bind to T (K11=1.8x10(6) M(-1) at 5 degrees C) over other nucleobases, and this is accompanied by significant quenching of its fluorescence. While the sensing functions depend on the flanking sequences to the AP site, Vitamin B2 is applicable to the detection of T/C (cytosine), T/G (guanine) and T/A (adenine) mutation sequences of the CYP2A6 gene, where the flanking nucleobases are guanines in both positions (-GXG-, X=AP site). PMID- 17723338 TI - Development of liposomal immunosensor for the measurement of insulin with femtomole detection. AB - The monitoring of insulin is of great relevance for the management of diabetes, the detection of pancreatic islet-cell malfunction, the definition of hypoglycemia, and the diagnosis of insulinoma. A liposomal immunosensing system for the determination of insulin was developed in this study. The insulin sensor was constructed by the immobilization of anti-insulin antibodies on the inner wall of the microcapillary immunoseparator. Liposomes tagged with anti-insulin and encapsulating a fluorescent dye were used as the detectable label. In the presence of insulin, sandwich immunocomplexes were formed between the immobilized antibodies in the column, the sample of insulin, and the antibody-tagged sulforhodamine B-dye-loaded liposomes. Signals generated by lysing the bound liposomes with 30 mM n-octyl-beta-D-glucopyranoside were measured by a fluorescence detector. The detected signal was directly proportional to the amount of insulin in the test sample. The liposomal immunosensing system successfully detected as low as 136 attomole. MeOH (30%) was used for the regeneration of antibody-binding sites in the microcapillary after each measurement, which allowed the immunoseparator to be used for at least 70 repeated assays. The antibody activity in this proposed microcapillary immunoseparator could be well maintained for at least 1 week. The calibration curve for insulin in Tris-buffered saline had a linear dynamic range of 10 pM-10 nM, and the total assay time was less than 30 min. The coefficient of variation for triplicate measurements was <5.00%, which indicated that well-reproducible results can be obtained by this newly developed method. PMID- 17723340 TI - Enrichment of N-terminal sulfonated peptides by a water-soluble fullerene derivative and its applications to highly efficient proteomics. AB - Recent studies have shown that N-terminal sulfonation of tryptic peptides by various sulfonating molecules greatly improves their post-source decay processes (e.g., in matrix-assisted laser desorption ionization) or the gas phase fragmentation processes (e.g., in tandem mass spectrometer), enhancing the ability to identify their sequences de novo. In the present work, we have demonstrated that incorporation of water-soluble C60-N,N-dimethylpyrrolidinium iodide selectively precipitates the 4-sulfophenyl isothiocyanate-modified peptide (SPITC-GGYR, SPITC-ASHLGLAR) by forming a noncovalent ion pair to the SO3- group of the SPITC, and thereby the C60 derivative can be utilized to enrich the modified peptide. Electrospray ionization (ESI) mass analyses show that the cationic SPITC-GGYR and SPITC-ASHLGLAR species are well separated from unmodified peptides and the modified peptides are subsequently detached from the C60 derivative upon using an acidic solution. PMID- 17723341 TI - A highly stable and sensitive chemically modified screen-printed electrode for sulfide analysis. AB - We report here a highly stable and sensitive chemically modified screen-printed carbon electrode (CMSPE) for sulfide analysis. The CMSPE was prepared by first ion-exchanging ferricyanide into a Tosflex anion-exchange polymer and then sealing with a tetraethyl orthosilicate sol-gel layer. The sol-gel overlayer coating was crucial to stabilize the electron mediator (i.e., Fe(CN)6(3-)) from leaching. The strong interaction between the oxy-hydroxy functional group of sol gel and the hydrophilic sites of Tosflex makes the composite highly rigid to trap the ferricyanide mediator. An obvious electrocatalytic sulfide oxidation current signal at approximately 0.20 V versus Ag/AgCl in pH 7 phosphate buffer solution was observed at the CMSPE. A linear calibration plot over a wide range of 0.1 microM to 1mM with a slope of 5.6 nA/muM was obtained by flow injection analysis. The detection limit (S/N=3) was 8.9 nM (i.e., 25.6 ppt). Practical utility of the system was applied to the determination of sulfide trapped from cigarette smoke and sulfide content in hot spring water. PMID- 17723342 TI - A microfluidic chip based liquid-liquid extraction system with microporous membrane. AB - A robust and simple approach for microfabricated chip based liquid-liquid extraction was developed for on-chip sample pretreatment. The chip based extraction system was composed of two microfabricated glass plates with a microporous membrane sandwiched in between. A simple bonding approach using epoxy was used to achieve bonding and sealing of the L-L extraction chip. Gravity was employed to drive the aqueous and organic flows through separate channels in the extraction system, separated by the membrane. During extraction, the analyte in an aqueous sample stream was transferred through the membrane into the organic stream. The fluorescence intensity of the analyte extracted into the organic stream was monitored in situ by a laser induced fluorescence detection system. The performance of the system was demonstrated using an aqueous solution of butyl rhodamine B (BRB) and isobutanol as sample and extractant, respectively. The system proved to be an efficient means for achieving chip based microporous membrane liquid-liquid extraction. The precision of fluorescence measurements was 1.5% R.S.D. (n=4). A linear response range of 1x10(-7) to 1 x 10(-4) M BRB was obtained with a regression equation: I=8.00 x 10(6) C + 4.91. An enrichment factor of ca. 3 was obtained with an extraction efficiency of 69%. PMID- 17723343 TI - Extraction mechanisms of charged organic dye molecules into silica-surfactant nanochannels in a porous alumina membrane. AB - Extraction mechanisms of charged organic dye molecules are examined for an assembly of silica-surfactant nanochannels with a channel diameter of 3.4 nm, which is formed inside the pores of an anodic alumina membrane by a surfactant template method. Experimental results confirm that the extraction mechanism depends on the sign of a charge of the dye molecules. The extraction of the cationic rhodamine 6G is predominantly caused by an ion-pair extraction process, whereas an anion-exchange process is mainly responsible for the extraction of the anionic sulforhodamine B. These extraction mechanisms are discussed by considering the microstructures of the silica-surfactant nanochannels. PMID- 17723344 TI - Integration of multiple-ion-sensing on a capillary-assembled microchip. AB - Multiple-ion-sensing functions are integrated on a capillary-assembled microchip (CAs-CHIP). Since the CAs-CHIPs are fabricated by embedding various chemically functionalized square capillaries onto a lattice PDMS channel plate having same channel dimensions as outer dimensions of square capillaries, integration of parallel multiple-ion-sensing is easily realized. Here, three ion-sensing capillaries are prepared and used for integrating these functions onto a single microchip. Ion-sensing square capillaries (sodium, potassium, calcium) are prepared by attaching ion-selective optode membranes to inner wall of capillaries, and are characterized in terms of response time, response range, and ion selectivity. Finally, fully characterized ion-sensing capillaries are embedded into PDMS channel plate in parallel to fabricate a multiple-ion-sensing chip. The CAs-CHIP-based strategy is promising for integrating multiple chemical sensing functions onto a single microchip. PMID- 17723345 TI - Microbial detection in microfluidic devices through dual staining of quantum dots labeled immunoassay and RNA hybridization. AB - This paper reported the development of a microfludic device for the rapid detection of viable and nonviable microbial cells through dual labeling by fluorescent in situ hybridization (FISH) and quantum dots (QDs)-labeled immunofluorescent assay (IFA). The coin sized device consists of a microchannel and filtering pillars (gap=1-2 microm) and was demonstrated to effectively trap and concentrate microbial cells (i.e. Giardia lamblia). After sample injection, FISH probe solution and QDs-labeled antibody solution were sequentially pumped into the device to accelerate the fluorescent labeling reactions at optimized flow rates (i.e. 1 and 20 microL/min, respectively). After 2 min washing for each assay, the whole process could be finished within 30 min, with minimum consumption of labeling reagents and superior fluorescent signal intensity. The choice of QDs 525 for IFA resulted in bright and stable fluorescent signal, with minimum interference with the Cy3 signal from FISH detection. PMID- 17723346 TI - Hadamard transform capillary electrophoresis combined with laser-induced fluorometry using electrokinetic injection. AB - Hadamard transform capillary electrophoresis (HTCE) based on electrokinetic injection allows laser-induced fluorescence detection using a small laser, namely the laser-diode-pumped YAG laser, as an excitation source. A small hole is fabricated at the center of a capillary by laser ablation; this hole functions as an inlet port for a sample solution. Therefore, the sample solution can be introduced electrophoretically into the capillary through the small hole. Multiple sample injection is accomplished by introducing a buffer solution from the end of the capillary and the sample solution through the hole. Both solutions are injected using two sets of high-voltage power supplies and migrate toward the opposite end of the capillary. A fluorescent analyte, rhodamine B, is successfully detected in the case of both single and multiple injection according to the Hadamard sequence code. By transforming the data encoded by the Hadamard matrix, the decoded data showed an increase in the signal-to-noise (S/N) ratio by a factor of 9.8. In the case of the sample containing two amino acids labeled with rhodamine B isothiocyanate (RBITC), although the concentration of every component including free RBITC is lower than the concentration limit of detection obtained by single injection, a substantial improvement in the sensitivity is achieved and all components are identified by the Hadamard transform technique. PMID- 17723347 TI - Characterization of interaction property of multicomponents in Chinese Herb with protein by microdialysis combined with HPLC. AB - Interaction of traditional Chinese Herb Rhizoma Chuanxiong and protein was studied by microdialysis coupled with high performance liquid chromatography. Compounds in Rhizoma Chuanxiong, such as ferulic acid, senkyunolide A and 3 butylphthalide, were identified by HPLC, HPLC-MS and UV-vis. Microdialysis recoveries and binding degrees of compounds in Rhizoma Chuanxiong with human serum albumin (HSA) and other human plasma protein were determined: recoveries of microdialysis sampling ranged from 36.7 to 98.4% with R.S.D. below 3.1%; while binding to HSA ranged from 0 to 91.5% (0.3mM HSA) and from 0 to 93.5% (0.6mM HSA), respectively. Compared with HSA, most of compounds bound to human blood serum more extensively and the results showed that binding of these compounds in Rhizoma Chuanxiong was influenced by pH. Two compounds were found to bind to HSA and human blood serum, their binding degrees were consistent with ferulic acid and 3-butylphthalide, the active compounds in Rhizoma Chuangxiong. PMID- 17723348 TI - Silver-ion redox sensing based on colloid formation by gallate ester derivatives. AB - Plasmon absorption of silver colloid, which was formed by reduction of silver ion with compounds bearing gallate ester groups in ethanol, was observed by absorption spectroscopy. The time-dependent absorption of silver colloid was found, which shows that the silver colloid is unstable and easy to aggregate. It seemed that a calixarene derivative bearing two gallate ester groups was the most suitable for determining silver ion. In order to prevent the silver colloid aggregation, poly(N-vinylpyrrolidone) (PVP) was added into the solution at a constant time after the preparation of sample solutions. In the calibration graph, the absorbance increased with increasing silver ion concentration, especially in the concentration range of 2.00 x 10(-6) to 1.00 x 10(-5) M. It is possible to determine silver ion concentrations using this method. PMID- 17723349 TI - Determination of sulfite in beer samples using an amperometric fill and flow channel biosensor employing sulfite oxidase. AB - A simple method is described to determine sulfite in beer samples using a fill and flow channel biosensor. A droplet of sample is placed into the inlet of a rectangular flow cell and begins to flow through the channel by capillarity. The flow is maintained and controlled by a porous outlet plug of defined porosity. In a rectangular flow cell, the sample solution flows through three consecutive zones: over a predictor electrode, an enzyme layer and a detector electrode. Together these three zones enable the differentiation between current due to sulfite and current due to other electroactive species in the sample. The predictor electrode is located upstream, and on the opposite channel wall to the enzyme layer and detector electrode, and is poised at the same potential (+0.65 V versus Ag/AgCl) as the detector electrode. On this electrode, the current contribution from all species in the sample solution that are oxidized at that potential is determined. The enzyme layer contains sulfite oxidase, which, in the process of oxidizing sulfite, produces hydrogen peroxide, which itself is reduced by excess sulfite. The current at the downstream detector electrode is therefore different from that at the predictor electrode as a result of the enzyme reaction and the difference of the currents, corrected for the dimensions of the electrodes, is proportional to the concentration of sulfite. The method enables a straightforward correction of the interfering current at the detector electrode and a determination of the analyte concentration. The effect of interferences from ascorbic acid, ethanol, sorbic acid and tartaric acid in the detection of sulfite is efficiently removed. The concentration of sulfite in a sample of beer measured by the biosensor is equivalent to that measured using a reference method based on the AOAC-recommended Monier-Williams method. PMID- 17723350 TI - Parametric studies of matched filters to enhance the signal-to-noise ratios of LC MS-MS peaks. AB - Chromatographic parameters of reference signals employed in matched filter methods have been studied using numerical experiments to improve the signal-to noise (S/N) ratios of small liquid chromatography (LC) peaks obtained with electrospray tandem mass spectrometers (MS-MS). These parameters include the width, shape, and S/N ratios of chromatographic peaks used as the reference signal profiles. Our results show the effect of reference peak widths on improving the S/N ratio of chromatographic peaks; the influence of reference peak shapes is negligible. To verify simulation results, various reference signals, including analyte peaks of high concentration standards, internal standard peaks, and artificial Gaussian peaks of different widths, have been employed to enhance signal peaks on real liquid chromatography-tandem mass spectrometry (LC-MS-MS) chromatograms via matched filter methods. Our experimental results demonstrate that the S/N ratio enhancement of chromatographic peaks agree with the simulation predictions. These findings, therefore, suggest that regardless of peak shape, a well-smooth peak with a width close to that of the analyte peak is an adequate reference signal, when matched filter methods are used to improve LC-MS-MS chromatograms. Nevertheless, all methods processed LC-MS-MS peaks in this study do not achieve the ideal improvement ratios estimated with simulation results. We attribute this deficiency to spike-like noise, which have considerable low frequency components riding on LC-MS-MS chromatograms. Matched filtering, which works as a low-pass filter in the frequency domain, cannot effectively eliminate low frequency flicker noise contributed by these spikes. In addition, simple median filtering does not provide adequate improvement despite being able to smooth out most spikes in the chromatograms. PMID- 17723352 TI - Determination of critical micelle concentrations and aggregation numbers by fluorescence correlation spectroscopy: aggregation of a lipopolysaccharide. AB - Fluorescence correlation spectroscopy (FCS) is often used to determine the mass or radius of a particle by using the dependence of the diffusion coefficient on the mass and shape. In this article we discuss how the particle size of aggregates can be measured by using the concentration dependence of the amplitude of the autocorrelation function (ACF) instead of the temporal decay. We titrate a solution of aggregates or micelles with a fluorescent label that possesses a high affinity for these structures and measure the changes in the amplitude of the ACF. We develop the theory describing the change of the ACF amplitude with increasing concentrations of labels and use it to fit experimental data. It is shown how this method can determine the aggregation number and critical micelle concentration of a standard detergent nonaethylene glycol monododecyl ether (C12E9) and a lipopolysaccharide (LPS: Escherichia coli 0111:B4). PMID- 17723351 TI - Simple and robust near-infrared spectroscopic monitoring of indium-tin-oxide (ITO) etching solution using Teflon tubing. AB - The ability to monitor etching solutions using a spectroscopy directly through existing Teflon lines in electronic industries is highly beneficial and offers many advantages. A monitoring method was developed using near-infrared (NIR) measurements with Teflon tubing as a sample container for the quantification of components in the indium-tin-oxide (ITO) etching solution composed of hydrochloric acid (HCl), acetic acid (CH3COOH) and water. Measurements were reproducible and it was possible to use the same calibration model for different Teflon tubings. Even though partial least squares (PLS) calibration performance was slightly degraded for Teflon cells when compared to quartz cells of the similar pathlength, the calibration data correlated well with reference data. The robustness of Teflon-based NIR measurement was evaluated by predicting the spectra of 10 independent samples that were collected using five different Teflon tubes. Although, two Teflon tubes were visually less transparent than the other three, there was no significant variation in the standard error of predictions (SEPs) among the five Teflon tubes. Calibration accuracy was successfully maintained and highly repeatable prediction results were achieved. This study verifies that a Teflon-based NIR measurement is reliable for the monitoring of etching solutions and it can be successfully integrated into on-line process monitoring. PMID- 17723353 TI - Determination of molecular weight profile for a bioactive beta-(1-->3) polysaccharides (Curdlan). AB - This paper focuses on the development of methodology based on MALDI-TOF mass spectrometry for evaluation of molecular weight profile of the water-insoluble portion of an extracellular polysaccharide, i.e. Curdlan. As previously demonstrated, MALDI analysis of water-insoluble Curdlan fraction gave number average (M(n)) and weight-average (M(w)) molecular weights of 8000 and 8700 Da, respectively [T.W.D. Chan, K.Y. Tang, Rapid Commun. Mass Spectrom. 17 (2003) 887]. To validate the MALDI determined molecular weight information, several additional analytical schemes were used to analysis the water-insoluble Curdlan fraction. In all cases, the water-insoluble Curdlan sample was fractionated by gel permeation chromatography (GPC) using Sephadex G-75 column. The M (n) of low mass and narrow distributed polysaccharide fractions were obtained by MALDI-MS. Good linearity was found in the calibration plot constructed from the measured M (n)-values and the corresponding elution time/volume. The relative quantity of various fractionated samples was then measured using three different approaches. These include (a) direct refractometric analysis; (b) UV-vis absorption analysis of the Aniline Blue stained sample; and (c) GC-MS analysis of the hydrolyzed and TMS-derivatized sample. Using results obtained from theses quantification methods and the correlation function between the GPC retention time and M (n), the MW and MWD of water-insoluble Curdlan were obtained. Our results demonstrated that the previous use of MALDI methods for measuring M(n), M(w) and polydispersity (PD) of water-insoluble Curdlan (with and without GPC fractionation) were unreliable. However, by standardizing the narrow distributed polysaccharides using MALDI-MS method, reliable molecular weight information for dispersed polysaccharides could be obtained. The M (n),M (w) and PD of the water-insoluble Curdlan were found to be 22,000, 31,500 Da and 1.40, respectively. PMID- 17723354 TI - Improved analysis of membrane protein by PVDF-aided, matrix-assisted laser desorption/ionization mass spectrometry. AB - Characterization of membrane proteins remains an analytical challenge because of difficulties associated with tedious isolation and purification. This study presents the utility of the polyvinylidene difluoride (PVDF) membrane for direct sub-proteome profiling and membrane protein characterization by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). The hydrophobic adsorption of protein, particularly membrane proteins, on the PVDF surface enables efficient on-PVDF washing to remove high concentrations of detergents and salts, such as up to 5% sodium dodecyl sulfate (SDS). The enhanced spectrum quality for MALDI detection is particularly notable for high molecular weight proteins. By using on-PVDF washing prior to MALDI detection, we obtained protein profiles of the detergent-containing and detergent-insoluble membrane fractions from Methylococcus capsulatus (Bath). Similar improvements of signal-to-noise ratios were shown on the MALDI spectra for proteins electroblotted from SDS polyacrylamide gel electrophoresis (SDS-PAGE) onto the PVDF membrane. We have applied this strategy to obtain intact molecular weights of the particulate methane monooxygenase (pMMO) composed of three intrinsic membrane-bound proteins, PmoA, PmoB, and PmoC. Together with peptide sequencing by tandem mass spectrometry, post-translational modifications including N-terminal acetylation of PmoA and PmoC and alternative C-terminal truncation of PmoB were identified. The above results show that PVDF-aided MALDI-MS can be an effective approach for profiling and characterization of membrane proteins. PMID- 17723355 TI - Simultaneous spectrophotometric determination of iron, nickel and cobalt in micellar media by using direct orthogonal signal correction-partial least squares method. AB - A very simple and selective spectrophotometric method for simultaneous determination of iron(II), nickel(II) and cobalt(II) based on formation of their complexes with 1-(2-pyridylazo)-2-naphtol (PAN) in micellar media is described. Although the complexes of Fe(II), Ni(II) and Co(II) with reagent show a spectral overlap, they have been simultaneously determined by partial least squares (PLS) with and without preprocessing step using direct orthogonal signal correction (DOSC). The linear range was 0.30-4.50 microg ml(-1) for Co(II), 0.20-3.00 microg ml(-1) for Ni(II) and 0.30-5.00 microg ml(-1) for Fe(II). The results obtained by the PLS and DOSC-PLS were statistically compared. Interference effects of common anions and cations were studied and the proposed method was also applied satisfactorily to the determination of Fe(II), Ni(II) and Co(II) in synthetic samples. PMID- 17723356 TI - High-resolution protein hydration NMR experiments: probing how protein surfaces interact with water and other non-covalent ligands. AB - High-resolution solution NMR experiments are extremely useful to characterize the location and the dynamics of hydrating water molecules at atomic resolution. However, these methods are severely limited by undesired incoherent transfer pathways such as those arising from exchange-relayed intra-molecular cross relaxation. Here, we review several complementary exchange network editing methods that can be used in conjunction with other types of NMR hydration experiments such as magnetic relaxation dispersion and 1J(NC') measurements to circumvent these limitations. We also review several recent contributions illustrating how the original solution hydration NMR pulse sequence architecture has inspired new approaches to map other types of non-covalent interactions going well beyond the initial scope of hydration. Specifically, we will show how hydration NMR methods have evolved and have been adapted to binding site mapping, ligand screening, protein-peptide and peptide-lipid interaction profiling. PMID- 17723357 TI - Analysis of protein interaction networks using mass spectrometry compatible techniques. AB - The ability to map protein-protein interactions has grown tremendously over the last few years, making it possible to envision the mapping of whole or targeted protein interaction networks and to elucidate their temporal dynamics. The use of mass spectrometry for the study of protein complexes has proven to be an invaluable tool due to its ability to unambiguously identify proteins from a variety of biological samples. Furthermore, when affinity purification is combined with mass spectrometry analysis, the identification of multimeric protein complexes is greatly facilitated. Here, we review recent developments for the analysis of protein interaction networks by mass spectrometry and discuss the integration of different bioinformatic tools for predicting, validating, and managing interaction datasets. PMID- 17723358 TI - Proteomics in cancer research: methods and application of array-based protein profiling technologies. AB - With the human genome sequence now determined, the field of molecular medicine is moving beyond genomics to proteomics, the large-scale analysis of proteins. It is now possible to examine the expression of more than 1000 proteins using mass spectrometry technology coupled with various separation methods. Microarray technology is a new and efficient approach, for extracting relevant biomedical data and has a wide range of applications. It provides a versatile tool to study protein-protein, protein-nucleic acid, protein-lipid, enzyme-substrate and protein-drug interactions. This review paper will explore the key themes in proteomics and their application in clinical cancer research. PMID- 17723359 TI - Duplexed sandwich immunoassays on a fiber-optic microarray. AB - In this paper, we describe a duplexed imaging optical fiber array-based immunoassay for immunoglobulin A (IgA) and lactoferrin. To fabricate the individually addressable array, microspheres were functionalized with highly specific monoclonal antibodies. The microspheres were loaded in microwells etched into the distal face of an imaging optical fiber bundle. Two microsphere-based sandwich immunoassays were developed to simultaneously detect IgA and lactoferrin, two innate immune system proteins found in human saliva. Individual microspheres could be interrogated for the simultaneous measurement of both proteins. The working concentration range for IgA detection was between 700 pM and 100 nM, while the working concentration range for lactoferrin was between 385 pM and 10 nM. The cross-reactivity between detection antibodies and their non specific targets was relatively low in comparison to the signal generated by the specific binding with their targets. These results suggest that the degree of multiplexing on this fiber-optic array platform can be increased beyond a duplex. PMID- 17723360 TI - Active bead-linked immunoassay on protein microarrays. AB - Protein microarrays are becoming a powerful tool in proteome, biochemical, and clinical studies. In addition to the quality of arrayed immobilized probe molecules, sensitivity of the microarray-based assay is highly dependent on the detection technique. Here we suggest four simple techniques for rapid detection of analytes bound to protein microarrays. The techniques employ functionalized magnetic and non-magnetic beads moved to, from, or along the array surface by external forces. In contrast to other labeling techniques actively controlled physical labels: (i) make detection extremely fast to allow microarray reading in seconds; (ii) provide a low background due to active removal of weakly bound beads; and (iii) provide a highly sensitive detection, since one antigen-antibody bond is capable of holding bead immobilized on the array surface. In combination with the electrophoretically assisted active immunoassay we described recently such active reading allows to reduce total indirect immunoassay time to 7-10 min while having sensitivity in the femtomolar concentration range. High speed, sensitivity, and specificity make active bead-linked detection an ideal choice in rapid high-throughput screening and in emergency diagnostics. PMID- 17723361 TI - Microarray techniques for more rapid protein quantification: use of single spot multiplex analysis and a vibration reaction unit. AB - Protein microarray technology is a powerful, popular tool for the high-throughput analysis of protein interactions. One important use for protein microarray technology is protein quantification by immunoassay, which was originally based on enzyme linked immunosorbent assay (ELISA) methods. Recently, new research and diagnostic applications have created a need for a rapid and easily applied high throughput protein quantification method. Here, we introduce several novel techniques that address these needs. Our improved protein microarray-based sandwich immunoassay techniques allow researchers to: (1) control the size and shape of protein spots on the microarray using a perforated seal; (2) analyze two proteins within a single spot, thus increasing the number of tests run on a single microarray without increasing the number of protein spots; (3) improve the efficiency and speed of the Ag-Ab interaction through vibratory reagent convection, which increased the signal intensity by more than two-fold and decreased the reaction time from 30 to 10 min. These new techniques will facilitate rapid immunoassays for diagnostic purposes and other research areas utilizing protein microarray analysis, such as investigations of ligand-receptor or protein-small molecule interactions. PMID- 17723362 TI - Templated xerogels as platforms for biomolecule-less biomolecule sensors. AB - We report on a new sensor strategy that we have termed protein imprinted xerogels with integrated emission sites (PIXIES). The PIXIES platform is completely self contained, and it achieves analyte recognition without a biorecognition element (e.g., antibody). The PIXIES relies upon sol-gel-derived xerogels, molecular imprinting, and the selective installation of a luminescent reporter molecule directly within the molecularly imprint site. In operation the templated xerogel selectively recognizes the target analyte, the analyte binds to the template site, and binding causes a change in the physicochemical properties within the template site that are sensed and reported by the luminescent probe molecule. We report the PIXIES analytical figures of merit for and compare these results to a standard ELISA. For human interleukin-1 the PIXIES-based sensor elements exhibited the following analytical figures of merit: (i) approximately 2 pg/mL detection limits; (ii) <2 min response times; (iii) >85 selectivity; (iv) <6% R.S.D. long term drift over 16 weeks of ambient storage; (v) >95% reversibility after more than 25 cycles; and (vi) >85% recoveries on spiked samples. PMID- 17723363 TI - Increasing robustness and sensitivity of protein microarrays through microagitation and automation. AB - Assay systems that employ protein microarrays for the analysis of complex samples are powerful tools to generate a high amount of data from a limiting amount of sample. Due to miniaturization, these systems are susceptible to fluctuations during signal generation and the use of uniform conditions for sample incubation and during the assay procedure is required to get reproducible results. Diffusion limits may prevent constant conditions on all parts of the array and can lead to the decease of the sensitivity of the array. Therefore, we set-up an automated assay system integrating a novel microagitation device using surface acoustic wave (SAW) technology. Multiplexed assays for the detection of autoantibodies from human serum and sandwich immunoassay for the detection of matrix metalloproteases (MMPs) were used to evaluate the system. Diffusion-rate limited solid phase reactions were enhanced by microagitation using the SAW technology resulting in up to three-fold higher signals. PMID- 17723365 TI - Optimization of aptamer microarray technology for multiple protein targets. AB - Aptamer-based microarrays for the quantitation of multiple protein analytes have been developed. A multiplex aptamer microarray was generated by printing two RNA aptamers (anti-lysozyme and anti-ricin) and two DNA aptamers (anti-IgE and anti thrombin) on to either streptavidin (SA) or neutravidin (NA)-coated glass slides. However, substantial optimization was required in order to ensure the simultaneous function of the aptamer:analyte pairs. The effects of protein labeling, assay buffer, surface coating, and immobilization chemistry and orientation were investigated. A single buffer (PBS buffer containing 5 mM MgCl2 and 0.1% Tween 20) was found to work well with all the aptamers, even though this was not the buffer originally used in their selection, while neutravidin-coated slides yielded a lower detection limit, wider detection range, and more uniform background than streptavidin-coated slides. Incubation with Cy3-labeled proteins yielded sensitive, target-specific, and dose-dependent responses to each protein. Target protein concentrations as low as 72 pg/mL (5 pM, lysozyme), 15 ng/mL (0.5 nM, ricin), 1.9 ng/mL (0.01 nM, IgE), and 170 ng/mL (5 nM, thrombin) could be detected. These results show that aptamer arrays can potentially be used with numerous proteins in parallel, furthering the notion that aptamer arrays may be useful in proteomics. PMID- 17723366 TI - Selection of aptamers by systematic evolution of ligands by exponential enrichment: addressing the polymerase chain reaction issue. AB - Aptamers are DNA oligonucleotides capable of binding different classes of targets with high affinity and selectivity. They are particularly attractive as affinity probes in multiplexed quantitative analysis of proteins. Aptamers are typically selected from large libraries of random DNA sequences in a general approach termed systematic evolution of ligands by exponential enrichment (SELEX). SELEX involves repetitive rounds of two processes: (i) partitioning of aptamers from non-aptamers by an affinity method and (ii) amplification of aptamers by the polymerase chain reaction (PCR). New partitioning methods, which are characterized by exceptionally high efficiency of partitioning, have been recently introduced. For the overall SELEX procedure to be efficient, the high efficiency of new partitioning methods has to be matched by high efficiency of PCR. Here we present the first detailed study of PCR amplification of random DNA libraries used in aptamer selection. With capillary electrophoresis as an analytical tool, we found fundamental differences between PCR amplification of homogeneous DNA templates and that of large libraries of random DNA sequences. Product formation for a homogeneous DNA template proceeds until primers are exhausted. For a random DNA library as a template, product accumulation stops when PCR primers are still in excess of the products. The products then rapidly convert to by-products and virtually disappear after only 5 additional cycles of PCR. The yield of the products decreases with the increasing length of DNA molecules in the library. We also proved that the initial number of DNA molecules in PCR mixture has no effect on the by-products formation. While the increase of the Taq DNA polymerase concentration in PCR mixture selectively increases the yield of PCR products. Our findings suggest that standard procedures of PCR amplification of homogeneous DNA samples cannot be transferred to PCR amplification of random DNA libraries: to ensure efficient SELEX, PCR has to be optimized for the amplification of random DNA libraries. PMID- 17723367 TI - Development of immobilized membrane-based affinity columns for use in the online characterization of membrane bound proteins and for targeted affinity isolations. AB - Membranes obtained from cell lines that express or do not express a target membrane bound protein have been immobilized on a silica-based liquid chromatographic support or on the surface of an activated glass capillary. The resulting chromatographic columns have been placed in liquid chromatographic systems and used to characterize the target proteins and to identify small molecules that bind to the target. Membranes containing ligand gated ion channels, G-protein coupled receptors and drug transporters have been prepared and characterized. If a marker ligand has been identified for the target protein, frontal or zonal displacement chromatographic techniques can be used to determine binding affinities (K(d) values) and non-linear chromatography can be used to assess the association (k(on)) and dissociation (k(off)) rate constants and the thermodynamics of the binding process. Membrane-based affinity columns have been created using membranes from a cell line that does not express the target protein (control) and the same cell line that expresses the target protein (experimental) after genomic transfection. The resulting columns can be placed in a parallel chromatography system and the differential retention between the control and experimental columns can be used to identify small molecules and protein that bind to the target protein. These applications will be illustrated using columns created using cellular membranes containing nicotinic acetylcholine receptors and the drug transporter P-glycoprotein. PMID- 17723368 TI - Immobilized enzyme reactor chromatography: optimization of protein retention and enzyme activity in monolithic silica stationary phases. AB - Our group recently reported on the application of protein-doped monolithic silica columns for immobilized enzyme reactor chromatography, which allowed screening of enzyme inhibitors present in mixtures using mass spectrometry for detection. The enzyme was immobilized by entrapment within a bimodal meso/macroporous silica material prepared by a biocompatible sol-gel processing route. While such columns proved to be useful for applications such as screening of protein-ligand interactions, significant amounts of entrapped proteins leached from the columns owing to the high proportion of macropores within the materials. Herein, we describe a detailed study of factors affecting the morphology of protein-doped bioaffinity columns and demonstrate that specific pH values and concentrations of poly(ethylene glycol) can be used to prepare essentially mesoporous columns that retain over 80% of initially loaded enzyme in an active and accessible form and yet still retain sufficient porosity to allow pressure-driven flow in the low muL/min range. Using the enzyme gamma-glutamyl transpeptidase (gamma-GT), we further evaluated the catalytic constants of the enzyme entrapped in capillary columns with different silica morphologies as a function of flowrate and backpressure using the enzyme reactor assay mode. It was found that the apparent activity of the enzyme was highest in mesoporous columns that retained high levels of enzyme. In such columns, enzyme activity increased by approximately 2 fold with increases in both flowrate (from 250 to 1000 nL/min) and backpressure generated (from 500 to 2100 psi) during the chromatographic activity assay owing to increases in k(cat) and decreases in K(M), switching from diffusion controlled to reaction controlled conditions at ca. 2000 psi. These results suggest that columns with minimal macropore volumes (<5%) are advantageous for the entrapment of soluble proteins for bioaffinity and bioreactor chromatography. PMID- 17723364 TI - Advances in cancer tissue microarray technology: Towards improved understanding and diagnostics. AB - Over the past few years, tissue microarray (TMA) technology has been established as a standard method for assessing the expression of proteins or genes across large sets of tissue specimens. It is being adopted increasingly among leading research institutions around the world and utilized in cancer research in parallel with the cDNA microarray technology. This article summarizes various aspects of cancer understanding and diagnostics in which TMA has had great impact. Although tremendous advances continue to be made to facilitate imaging and archiving of TMA specimens, automatic evaluation and quantitative analysis of TMA still remains an important challenge for modern investigators. PMID- 17723369 TI - Protein digestion and phosphopeptide enrichment on a glass microchip. AB - This work describes an integrated glass microdevice for proteomics, which directly couples proteolysis with affinity selection. Initial results with standard phosphopeptide fragments from beta-casein in peptide mixtures showed selective capture of the phosphorylated fragments using immobilized metal affinity chromatography (IMAC) beads packed into a microchannel. Complete selectivity was seen with angiotensin, with capture of only the phosphorylated form. On-chip proteolysis, using immobilized trypsin beads packed into a separate channel, was directly coupled to the phosphopeptide capture and the integrated devices evaluated using beta-casein. Captured and eluted fragments were analyzed using both capillary electrophoresis (CE) and capillary liquid chromatography/mass spectrometry (cLC/MS). The results show selective capture of only phosphopeptide fragments, but incomplete digestion of the protein was apparent from multiple peaks in the CE separations. The MS analysis indicated a capture bias on the IMAC column for the tetraphosphorylated peptide fragment over the monophosphorylated fragment. Application to digestion and capture of a serum fraction showed capture of material; however, non-specific binding was evident. Additional work will be required to fully optimize this system, but this work represents a novel sample preparation method, incorporating protein digestion on line with affinity capture for proteomic applications. PMID- 17723370 TI - Creating hierarchical models of protein families based on Expressed Sequence Tags: the "Sprockets" analysis pipeline. AB - We have created an analysis pipeline called Sprockets, which can be used to classify proteins into various hierarchical "families", and build searchable models of these families. The construction of these families is based on data from Expressed Sequence Tags (ESTs) and Coding DNA Sequences (CDSs), making Sprockets clusters especially suitable for studying gene families in organisms for which the completely sequenced genome does not (yet) exist. The pipeline consists of two main parts: pair-wise analysis and grouping of sequences with Z score statistics, followed by hierarchical splitting of clusters into alignable protein families. Various computational and statistical techniques applied in Sprockets allow it to act like a massive and selective multiple sequence alignment engine for combining individual sequence collections and related public sequences. The end result is a database of gene Hidden Markov Models, each related to the other by three levels of similarity: secondary structure, function and evolutionary origin. For a sample 20,000 EST set from Lactuca spp., Sprockets provided a 9% improvement in mapping of function to unknown sequences over traditional pair-wise search methods and InterPro mapping. PMID- 17723371 TI - Perchlorate: an enigma for the new millennium. PMID- 17723373 TI - Risk assessment, remedial decisions and the challenge to protect public health: the perchlorate case study. AB - While scientists have a responsibility to defer judgment in the absence of conclusive data, public health and ecological protection require that government regulators make decisions based on available information. The risk assessment paradigm has evolved to help risk managers balance risks to public health with the cost of pollution control and remediation. Risk assessments are designed to be reasonably protective of public health, however the time and money required to develop and evaluate a robust scientific database can significantly delay regulatory action while exposures continue. The federal assessment of perchlorate, a component of rocket fuel and a thyroid toxicant, is presented here as a case study that demonstrates some of the limitations of risk assessment in protecting public health. Perchlorate was detected in a city well field that lies beneath a military training range at Aberdeen Proving Ground, a U.S. Army garrison in Maryland. Cleanup was put on hold, pending promulgation of a national drinking water standard for perchlorate. This case study (1) illustrates the challenge of preventing chemical exposures in the absence of promulgated standards, and (2) makes recommendations for approaches to preventing exposures to chemicals of unknown, or uncertain toxicity before they occur. PMID- 17723372 TI - Environmental perchlorate: why it matters. AB - The only known mechanism of toxicity for perchlorate is interference with iodide uptake at the sodium-iodide symporter (NIS). The NIS translocates iodide across basolateral membranes to the thyroid gland so it can be used to form thyroid hormones (TH). NIS is also expressed in the mammary gland during lactation, so that iodide can be transferred from a mother to her child. Without adequate iodide, an infant cannot produce sufficient TH to meet its developmental needs. Effects expected from perchlorate are those that would be seen in conditions of hypothyroidism or hypothyroxinemia. The probability of a permanent adverse effect is greatest during early life, as successful neurodevelopment is TH-dependent. Study of perchlorate risk is complicated by a number of factors including thyroid status of the mother during gestation, thyroid status of the fetus, maternal and infant iodine intake, and exposure of each to other TH-disrupting chemicals. Perhaps the greatest standing issue, and the issue most relevant to the field of analytical chemistry, is the simple fact that human exposure has not been quantified. This review will summarize perchlorate's potential to adversely affect neurodevelopment. Whether current environmental exposures to perchlorate contribute to neuro-impairment is unknown. Risks posed by perchlorate must be considered in conjunction with iodine intake. PMID- 17723374 TI - Development of a drinking water regulation for perchlorate in California. AB - Perchlorate is an environmental contaminant often associated with military installations and rocket propellant manufacture and testing facilities across the U.S. Highly water soluble, perchlorate has been found by federal and state agencies at almost 400 sites within the U.S. in groundwater, surface water, soil or public drinking water. There is no federal drinking water standard for perchlorate, but it is on the drinking water Contaminant Candidate List, and falls under the Unregulated Contaminant Monitoring Rule (UCMR) for which monitoring is required. The recent National Academy of Science (NAS) report on the potential health effects of perchlorate recommended a perchlorate reference dose of 0.0007 mg/kg of body weight which would be equivalent to a drinking water concentration of 24.5 microg/L. In California, approximately 395 wells in 96 water systems have been shown to contain perchlorate, and about 90% of these are located in Southern California. Water taken from the Colorado River, a major surface water supply to Southern California, has had reported detections of perchlorate ranging from non-detect to 9 microg/L. California has established a Public Health Goal (PHG) of 6 microg/L for perchlorate, and a proposed drinking water regulation is imminent. This review details the regulatory process involved with particular attention given to the occurrence of perchlorate in California drinking water sources and analytical methodology utilized. PMID- 17723375 TI - Perchlorate and chlorate in dietary supplements and flavor enhancing ingredients. AB - The oxyhalide anions perchlorate and chlorate were measured in a series of dietary (vitamin and mineral) supplements and flavor enhancing ingredients collected from various commercial vendors in two large US cities. Analyses were conducted using liquid chromatography with tandem mass spectrometry (LC-MS/MS). The limit of detection was based on the mass of supplements and ingredients extracted and ranged from 2 to 15 ng/g for perchlorate and 4 to 30 ng/g for chlorate. Perchlorate and chlorate were detected in 20 and 26, respectively, of the 31 dietary supplements tested, with concentrations ranging from non detectable to as high as 2400 and 10,300 ng/g, respectively. Based upon the recommended dose provided by each manufacturer for different supplements, the daily oral dose of perchlorate and chlorate could be as high as 18 and 20 microg/day, respectively. The highest level of perchlorate was found in a supplement recommended for pregnant women as a prenatal nutritional supplement. Of the 31 dietary supplements investigated, 12 were specifically marketed for pregnant women and children. Perchlorate and chlorate were also detectable in four products marketed for the enhancement of food flavor. Perchlorate is found naturally in some parts of the world, is present in some natural fertilizers, is used as an oxidizer in solid fuel engines, and has been used at therapeutic doses in humans to treat overactive thyroid glands. Perchlorate has been detected in drinking water, dairy products, some produce and grains, and human breast milk. This is the first report of perchlorate measured in over-the-counter dietary supplements and flavor enhancing ingredients. PMID- 17723377 TI - Analysis of perchlorate in foods and beverages by ion chromatography coupled with tandem mass spectrometry (IC-ESI-MS/MS). AB - A new IC-ESI-MS/MS method, with simple sample preparation procedure, has been developed for quantification and confirmation of perchlorate (ClO4-) anions in water, fresh and canned food, wine and beer samples at low part-per-trillion (ng l(-1)) levels. To the best of our knowledge, this is the first time an analytical method is used for determination of perchlorate in wine and beer samples. The IC ESI-MS/MS instrumentation consisted of an ICS-2500 ion chromatography (IC) system coupled to either an API 2000 or an API 3200 mass spectrometer. The IC-ESI-MS/MS system was optimized to monitor two pairs of precursor and fragment ion transitions, i.e., multiple reaction monitoring (MRM). All samples had oxygen-18 isotope labeled perchlorate internal standard (ISTD) added prior to extraction. Chlorine isotope ratio (35Cl/37Cl) was used as a confirmation tool. The transition of 35Cl16O4- (m/z 98.9) into 35Cl16O3- (m/z 82.9) was monitored for quantifying the main analyte; the transition of 37Cl16O4- (m/z 100.9) into 37Cl16O3- (m/z 84.9) was monitored for examining a proper isotopic abundance ratio of 35Cl/37Cl; and the transition of 35Cl18O4- (m/z 107.0) into 35Cl18O3- (m/z 89.0) was monitored for quantifying the internal standard. The minimum detection limit (MDL) for this method in de-ionized water is 5 ng l(-1) (ppt) using the API 2000 mass spectrometer and 0.5 ng l(-1) using the API 3200 mass spectrometer. Over 350 food and beverage samples were analyzed mostly in triplicate. Except for four, all samples were found to contain measurable amounts of perchlorate. The levels found ranged from 5 ng l(-1) to 463.5+/-6.36 microg kg(-1) using MRM 98.9-->82.9 and 100 microl injection. PMID- 17723376 TI - Potential perchlorate exposure from Citrus sp. irrigated with contaminated water. AB - Citrus produced in the southwestern United States is often irrigated with perchlorate-contaminated water. This irrigation water includes Colorado River water which is contaminated with perchlorate from a manufacturing plant previously located near the Las Vegas Wash, and ground water from wells in Riverside and San Bernardino counties of California which are affected by a perchlorate plume associated with an aerospace facility once located near Redlands, California. Studies were conducted to evaluate the uptake and distribution of perchlorate in citrus irrigated with contaminated water, and estimate potential human exposure to perchlorate from the various citrus types including lemon (Citrus limon), grapefruit (Citrus paradise), and orange (Citrus sinensis) produced in the region. Perchlorate concentrations ranged from less than 2-9 microg/L for Colorado River water and from below detection to approximately 18 microg/L for water samples from wells used to irrigate citrus. Destructive sampling of lemon trees produced with Colorado River water show perchlorate concentrations larger in the leaves (1835 microg/kg dry weight (dw)) followed by the fruit (128 microg/kg dw). Mean perchlorate concentrations in roots, trunk, and branches were all less than 30 microg/kg dw. Fruit pulp analyzed in the survey show perchlorate concentrations ranged from below detection limit to 38 microg/kg fresh weight (fw), and were related to the perchlorate concentration of irrigation water. Mean hypothetical exposures (mug/person/day) of children and adults from lemons (0.005 and 0.009), grapefruit (0.03 and 0.24), and oranges (0.51 and 1.20) were estimated. These data show that potential perchlorate exposures from citrus in the southwestern United States are negligible relative to the reference dose recommended by the National Academy of Sciences. PMID- 17723378 TI - Photochemical formation of perchlorate from aqueous oxychlorine anions. AB - Evidence of atmospherically produced perchlorate is being accumulated, yet information regarding its formation process is largely unknown. For the first time, the present study demonstrates that perchlorate can be generated as an end product of photochemical transformation reactions of chlorine precursors such as aqueous salt solutions of hypochlorite, chlorite, and chlorate upon exposure to ultraviolet (UV) radiation. For example, under exposure to UV light from photochemical reactor lamps at a peak wavelength of 253.7 nm for 7 days, the observed perchlorate concentrations were 5, 25, and 626 microg/L at initial chlorite concentrations of 100, 1000, and 10,000 mg/L, respectively. In addition, perchlorate was generated within 7 days from aqueous chlorite solutions at mid latitude (33 degrees 59'N, 101 degrees 89'W) spring and summer solar radiation. Via UV radiation from the artificial lamps and sunlight, chlorite was converted to chloride (68%) and chlorate (32%) as end-products on the basis of molar percentage. However, perchlorate was not detected from aqueous chloride solutions at initial concentrations up to 10,000 mg/L under the experimental conditions. Relevant mechanistic pathways were proposed based on the fact that chlorine dioxide (as a primary intermediate) may play a significant role in phototransformation of the precursors leading to perchlorate. PMID- 17723379 TI - Approaches to sample pretreatment in the determination of perchlorate in real world samples. AB - Perchlorate can be determined by the tandem technique of ion chromatography (IC) coupled to electrospray ionization mass spectrometry (ESI-MS). However, detection by ESI-MS can be compromised by the coelution of matrix components that can suppress the analyte signal. In addition, the presence of surface-active and other types of matrix components can cause fouling of the electrospray inlet, reducing overall signal and requiring frequent maintenance. The influences of matrix components can be minimized by using analytical columns with different selectivities, in-line diversion of separated matrix components, and off-line selective removal of matrix components via ion exchange or adsorption. This paper will discuss these sample preparation approaches for samples containing anionic species including surfactants and inorganic ions that elute in the vicinity of perchlorate. PMID- 17723380 TI - Challenges in determining perchlorate in biological tissues and fluids: implications for characterizing perchlorate exposure. AB - The ability to measure environmental contaminants in biological tissues and fluids is important in the characterization of exposure. However, the analysis of certain contaminants in these matrices presents significant challenges. Perchlorate (ClO4-) has emerged as a potential contaminant of concern primarily in drinking water and also in contaminated food. Significant advances have been made in the analysis of perchlorate in environmental matrices (water, soil) by ion chromatography (IC). In contrast, the analysis of perchlorate in extracts of biological tissues and fluids (vegetation, organs, milk, blood, urine, etc.) presents several challenges including small sample sizes, extracts with high matrix conductivity, and co-elution of other ions during IC analysis. To be able to detect low concentrations of perchlorate in biological samples, interferences must be removed or minimized, such as through the use of preparative chromatography cleanup techniques and/or alternative analytical methods less susceptible to common interferences (preconcentration or mass spectrometric detection). We present discussion and examples of the challenges encountered in the analysis of tissue extracts and fluids for perchlorate by IC and how some of those analytical challenges have been overcome. PMID- 17723381 TI - Sample processing method for the determination of perchlorate in milk. AB - In recent years, many different water sources and foods have been reported to contain perchlorate. Studies indicate that significant levels of perchlorate are present in both human and dairy milk. The determination of perchlorate in milk is particularly important due to its potential health impact on infants and children. As for many other biological samples, sample preparation is more time consuming than the analysis itself. The concurrent presence of large amounts of fats, proteins, carbohydrates, etc., demands some initial cleanup; otherwise the separation column lifetime and the limit of detection are both greatly compromised. Reported milk processing methods require the addition of chemicals such as ethanol, acetic acid or acetonitrile. Reagent addition is undesirable in trace analysis. We report here an essentially reagent-free sample preparation method for the determination of perchlorate in milk. Milk samples are spiked with isotopically labeled perchlorate and centrifuged to remove lipids. The resulting liquid is placed in a disposable centrifugal ultrafilter device with a molecular weight cutoff of 10 kDa, and centrifuged. Approximately 5-10 ml of clear liquid, ready for analysis, is obtained from a 20 ml milk sample. Both bovine and human milk samples have been successfully processed and analyzed by ion chromatography mass spectrometry (IC-MS). Standard addition experiments show good recoveries. The repeatability of the analytical result for the same sample in multiple sample cleanup runs ranged from 3 to 6% R.S.D. This processing technique has also been successfully applied for the determination of iodide and thiocyanate in milk. PMID- 17723382 TI - Matrix interference free determination of perchlorate in urine by ion association ion chromatography-mass spectrometry. AB - Quantitative measurement of perchlorate in biological fluids is of importance to assess its toxicity and to study its effects on the thyroid gland. Whenever possible, urine samples are preferred in toxicologic/epidemiologic studies because sample collection is non-invasive. We present here a pretreatment method for the determination of perchlorate in urine samples that lead to a clean matrix. Urine samples, spiked with isotopically labeled perchlorate, are exposed to UV to destroy/decompose organic molecules and then sequentially treated with an H+-form cation exchange resin to remove protolyzable compounds, with ammonia to raise the pH to 10-11 and finally passed through a mini-column of basic alumina to remove the color and other organic matter. After filtration through a 0.45 microm syringe filter, the sample thus prepared can be directly injected into an ion chromatograph (IC). We use ion association-electrospray ionization mass spectrometry (ESI-MS) to detect and quantify perchlorate. The proposed sample preparation method leads to excellent limits of detection (LOD's) for perchlorate since there is essentially no dilution of sample and the matrix effects are eliminated. Results of urine samples from both men and women volunteers are reported for perchlorate, as well as for iodide and thiocyanate, which are generally present at much higher concentrations and for which a "dilute and shoot" approach is adequate. The limit of detection (S/N=3) for iodide, thiocyanate and perchlorate by the present method was 0.40, 0.10 and 0.080 microg l(-1), respectively. PMID- 17723383 TI - Analysis of perchlorate, thiocyanate, nitrate and iodide in human amniotic fluid using ion chromatography and electrospray tandem mass spectrometry. AB - Because of health concerns surrounding in utero exposure to perchlorate, we developed a sensitive and selective method for quantifying iodide, as well as perchlorate and other sodium-iodide symporter (NIS) inhibitors in human amniotic fluid using ion chromatography coupled with electrospray ionization tandem mass spectrometry. Iodide and NIS inhibitors were quantified using a stable isotope labeled internal standards (Cl18O4-, S13CN- and 15NO3- with excellent assay accuracy of 100%, 98%, 99%, 95% for perchlorate, thiocyanate, nitrate and iodide, respectively, in triplicate analysis of spiked amniotic fluid sample). Excellent analytical precision (<5.2% RSD for all analytes) was found when amniotic fluid quality control pools were repetitively analyzed for iodide and NIS-inhibitors. Selective chromatography and tandem mass spectrometry reduced the need for sample cleanup, resulting in a rugged and rapid method capable of routinely analyzing 75 samples/day. Analytical response was linear across the physiologically relevant concentration range for the analytes. Analysis of a set of 48 amniotic fluid samples identified the range and median levels for perchlorate (0.057-0.71, 0.18 microg/L), thiocyanate (<10-5860, 89 microg/L), nitrate (650-8900, 1620 microg/L) and iodide (1.7-170, 8.1 microg/L). This selective, sensitive, and rapid method will help assess exposure of the developing fetus to low levels of NIS-inhibitors and their potential to inhibit thyroid function. PMID- 17723384 TI - Streamlined sample preparation procedure for determination of perchlorate anion in foods by ion chromatography-tandem mass spectrometry. AB - A rapid, sensitive, and specific method was developed for the determination of perchlorate anion in foods. The foods included high moisture fruits and vegetables, low moisture foods (e.g. wheat flour and corn meal), and infant foods. Improvements to existing procedures were made in sample preparation that reduced sample test portion size from 100 to 5 or 10 g, extraction solvent volume from 150 to 20-40 ml, and replaced blending extraction-vacuum filtration and their associated large glassware with a simple shakeout-centrifugation in a small conical tube. Procedures common to all matrices involved: extraction, centrifugation, graphitized carbon solid phase extraction (SPE) cleanup, and ion chromatography-tandem mass spectrometry (IC-MS/MS) analysis. A Waters IC-Pak Anion HR column (4.6 mm x 75 mm) was eluted with 100mM ammonium acetate in 50:50 (v/v) acetonitrile/water mobile phase at a rate of 0.35 ml/min. A triple stage quadrupole mass spectrometer, equipped with electrospray ionization (ESI) in the negative ion mode, was used to detect perchlorate anion. An 18O4-labeled perchlorate anion internal standard was used to correct for any matrix effects. The method limit of quantitation (LOQ) was: 1.0 microg/kg in fruits, vegetables, and infant foods; 3.0 microg/kg in dry products. Fortified test portions gave 80 120% recoveries. Determination of incurred perchlorate anion residues agreed well with results for comparable commodities or products analyzed by published methods. PMID- 17723385 TI - Perchlorate in seawater: bioconcentration of iodide and perchlorate by various seaweed species. AB - There has been no reliable published data on the presence of perchlorate in seawater. Seaweeds are among the most important plant life in the ocean and are good sources of iodine and have been widely used as food and nutritional supplement. Perchlorate is known to inhibit the transport of iodide by the sodium iodide symporter (NIS), present e.g., in the thyroid and mammary glands. With perchlorate being increasingly detected in drinking water, milk and various other foods, increasing the iodide intake through inexpensive natural supplements may be an attractive solution for maintaining iodine assimilation. We report here measurable concentrations of perchlorate in several samples of seawater (detectable in about half the samples analyzed). We also report the iodide and perchlorate concentrations of 11 different species of seaweed and the corresponding bioconcentration factors (BCF) for perchlorate and iodide, relative to the seawater from which they were harvested. All seaweed samples came from the same region, off the coast of Northeastern Maine. Concentrations of iodide and perchlorate in four seawater samples collected from the region near harvest time were 30+/-11 and 0.16+/-0.084 microg l(-1), respectively. Concentrations of both iodide and perchlorate varied over a wide range for different seaweed species; iodide ranging from 16 to 3134 mg kg(-1) and perchlorate from 0.077 to 3.2 mg kg( 1). The Laminaria species had the highest iodide concentration; Laminaria digitata is the seaweed species most commonly used in the kelp tablets sold in health food stores. Our sample of L. digitata contained 3134+/-15 mg iodide/kg dry weight. The BCF varied widely for different species, with Laminaria species concentrating iodide preferentially over perchlorate. The iodide BCF (BCF(i)) to perchlorate BCF (BCF(p)) quotient ranged from 0.66 to 53; L. digitata and L. saccarina having a BCF(i)/BCF(p) value of 45 and 53, respectively, far greater than a simple anion exchange process will allow. Although most seaweed samples contain some amount of perchlorate, the great majority contains iodide in so much higher amount that at least for the commonly used Laminaria species, the iodide/perchlorate ratio is greater than the square of the perchlorate to iodide selectivity factor reported for the mammalian NIS and should thus lead to net beneficial iodine nutrition even in a two-stage mother-infant scenario. PMID- 17723386 TI - Stability of low levels of perchlorate in drinking water and natural water samples. AB - Perchlorate ion (ClO4-) is an environmental contaminant of growing concern due to its potential human health effects, impact on aquatic and land animals, and widespread occurrence throughout the United States. The determination of perchlorate cannot normally be carried out in the field. As such, water samples for perchlorate analysis are often shipped to a central laboratory, where they may be stored for a significant period before analysis. The stability of perchlorate ion in various types of commonly encountered water samples has not been generally examined-the effect of such storage is thus not known. In the present study, the long-term stability of perchlorate ion in deionized water, tap water, ground water, and surface water was examined. Sample sets containing approximately 1000, 100, 1.0, and 0.5 microg l(-1) perchlorate ion in deionized water and also in local tap water were formulated. These samples were analyzed by ion chromatography for perchlorate ion concentration against freshly prepared standards every 24h for the first 7 days, biweekly for the next 4 weeks, and periodically after that for a total of 400 or 610 days for the two lowest concentrations and a total of 428 or 638 days for the high concentrations. Ground and surface water samples containing perchlorate were collected, held and analyzed for perchlorate concentration periodically over at least 360 days. All samples except for the surface water samples were found to be stable for the duration of the study, allowing for holding times of at least 300 days for ground water samples and at least 90 days for surface water samples. PMID- 17723387 TI - Surface-enhanced Raman scattering for perchlorate detection using cystamine modified gold nanoparticles. AB - Perchlorate (ClO4-) has recently emerged as a widespread environmental contaminant found in groundwater and surface water, and there is a great need for rapid detection and monitoring of this contaminant. This study presents a new technique using cystamine-modified gold nanoparticles as a substrate for surface enhanced Raman scattering (SERS) detection of perchlorate at low concentrations. A detection limit of 5x10(-6) M (0.5 mg/L) has been achieved using this method without sample preconcentration. This result was attributed to a strong plasmon enhancement by gold metal surfaces and the electrostatic attraction of ClO4- onto positively charged, cystamine-modified gold nanoparticles at a low pH. The methodology also was found to be reproducible, quantitative, and not susceptible to significant interference from the presence of anions such as sulfate, phosphate, nitrate and chloride at concentrations <1 mM, making it potentially suitable for rapid screening and routine analysis of perchlorate in environmental samples. PMID- 17723388 TI - Development of gold-silica composite nanoparticle substrates for perchlorate detection by surface-enhanced Raman spectroscopy. AB - Surface-enhanced Raman spectroscopy (SERS) holds promise for rapid, in situ detection of perchlorate (ClO4-) in the environment if sensitive and reproducible SERS substrates can be developed. In this study, new, functionalized gold-silica (Au-SiO2) composite nanoparticles were synthesized and used as SERS substrates for ClO4- detection. These nanoparticles were composed of a silica core with Au nanoparticles grafted onto the SiO2 spheres by in situ chemical reduction of AuCl4- or physisorption of Au colloids. Chemical coupling agents with such functional groups as -N+(CH3)3 and -NH3+/-NH2 were used to enhance perchlorate sorption onto the substrate and therefore the detection of ClO4-. These new substrates were found to be optically stable and provide a greatly enhanced surface plasmon or SERS, resulting in a detection limit as low as 10(-6) M ClO4- (0.1 mg/L) in water. PMID- 17723389 TI - Rapid on-line preconcentration and suppressed micro-bore ion chromatography of part per trillion levels of perchlorate in rainwater samples. AB - The development of a rapid method for the determination of perchlorate in rain and drinking waters is presented. In the optimised method, an on-line preconcentration technique was employed utilising a 10 mm x 4.6 mm Phenomenex Onyx monolithic guard cartridge coated with (N-dodecyl-N,N dimethylammonio)undecanoate for selective preconcentration, with subsequent elution into a fixed volume injection loop ('heart-cut' of the concentrator column eluate) and separation using an IonPac AS16 (250 mm x 2mm) anion exchange column and a potassium hydroxide concentration gradient. Off-line optimisation studies showed that the coated monolith displayed near quantitative recovery up to 50 microg/L perchlorate level from standards prepared in reagent water. On line preconcentration of perchlorate obtained detection limits down to 56 ng/L in reagent water, between 70 and 80 ng/L in rainwater samples and 2.5 microg/L in non-pretreated drinking water. After an additional sample sulphate/carbonate removal step, low ng/L perchlorate concentrations could also be observed in drinking water. The complete on-line method exhibited reproducibility for n=10 replicate runs of R.S.D.< or =3% for peak height/area and R.S.D.=0.08% for retention time. The optimised method, of 20 min total duration, was applied to the determination of perchlorate by standard addition in 10 rainwater samples and one drinking water sample. Concentrations of perchlorate present ranged from below the detection limit for four rainwater samples, with another three samples showing perchlorate present at between 70 and 100 ng/L, and one sample showing perchlorate present at 2.8 microg/L. Levels of 1.1 microg/L in the drinking water sample were also recorded. PMID- 17723390 TI - Matrix diversion methods for improved analysis of perchlorate by suppressed ion chromatography and conductivity detection. AB - Two inline matrix diversion methods were developed for the sensitive analysis of perchlorate in a matrix comprising up to 1000 mg l(-1) of chloride, sulfate and bicarbonate ions using suppressed ion chromatography and conductivity detection. The first method used a cryptand C1 concentrator column, which exhibited a high selectivity for perchlorate ion over the other matrix anions. After retaining the sample anions in a concentrator column derivatized with a crytpand phase, a rinse step was implemented with a weak base to divert the matrix ions to waste while selectively retaining perchlorate in the concentrator column for subsequent analysis. The analysis was done using a 2mm IonPac AS16 or 2 mm IonPac AS20 separator column. The second method was a two-dimensional matrix diversion method with a focus on improving the detection sensitivity. The first dimension was used to achieve some resolution of the matrix ions from perchlorate. The perchlorate ion was then diverted into a concentrator column for subsequent analysis in the second dimension. By pursuing analysis using a 4mm IonPac AS16 or IonPac AS20 column in the first dimension and subsequently pursuing analysis using a 2mm IonPac AS16 or IonPac AS20 column format, excellent sensitivities were achieved when the first and second dimensions were operated at the same linear flow velocity (cm min(-1)). While sensitive detection of perchlorate in the low microg l(-1) regime was achieved by the above methods in the presence of matrix ions, superior recovery for perchlorate was demonstrated under a variety of matrix concentrations by the second method. PMID- 17723391 TI - Enzyme-amplified protein microarray and a fluidic renewable surface fluorescence immunoassay for botulinum neurotoxin detection using high-affinity recombinant antibodies. AB - Two immunoassay platforms were developed for either the sensitive or rapid detection of botulinum neurotoxin A (BoNT/A), using high-affinity recombinant monoclonal antibodies against the receptor binding domain of the heavy chain of BoNT/A. These antibodies also bind the same epitopes of the receptor binding domain present on a nontoxic recombinant heavy chain fragment used for assay development and testing in the current study. An enzyme-linked immunosorbent assay (ELISA) microarray using tyramide amplification for localized labeling was developed for the specific and sensitive detection of BoNT. This assay has the sensitivity to detect BoNT in buffer and blood plasma samples down to 14fM (1.4 pg mL(-1)). Three capture antibodies and one antibody combination were compared in the development of this assay. Using a selected pair from the same set of recombinant monoclonal antibodies, a renewable surface microcolumn sensor was developed for the rapid detection of BoNT/A in an automated fluidic system. The ELISA microarray assay, because of its sensitivity, offers a screening test with detection limits comparable to the mouse bioassay, with results available in hours instead of days. The renewable surface assay is less sensitive but much faster, providing results in less than 10 min. PMID- 17723392 TI - Developing an electrochemical deoxyribonucleic acid (DNA) biosensor on the basis of human interleukine-2 gene using an electroactive label. AB - Development of an electrochemical DNA biosensor based on a human interleukine-2 (IL-2) gene probe, using a pencil graphite electrode (PGE) as transducer and methylene blue (MB) as electroactive label is described. The sensor relies on the immobilization of a 20-mer single stranded oligonucleotide probe (hIL-2) related to the IL-2 gene on the electrode. The hybridization between the probe and its complementary sequence (chIL-2) as the target was studied by square wave voltammetry (SWV) of MB accumulated on the PGE. In this approach the extent of hybridization is evaluated on the basis of the difference between SWV signals of MB accumulated on the probe-PGE and MB accumulated on the probe-target-PGE. Some hybridization experiments with non-complementary oligonucleotides were carried out to assess whether the suggested DNA sensor responds selectively to the target. Some experimental variables affecting the performance of the biosensor including: polishing of PGE, its electrochemical activation conditions (i.e., activation potential and activation time) and probe immobilization conditions on the electrodes (i.e., immobilization potential and time) were investigated and the optimum values of 1.80 V and 300 s for PGE activation, and -0.5 V and 400s for the probe immobilization on the electrode were suggested. PMID- 17723393 TI - Self-assembling gold nanoparticles on thiol-functionalized poly(styrene-co acrylic acid) nanospheres for fabrication of a mediatorless biosensor. AB - A novel strategy to construct a sensitive mediatorless sensor of H2O2 was described. At first, a cleaned gold electrode was immersed in thiol functionalized poly(styrene-co-acrylic acid) (St-co-AA) nanosphere latex prepared by emulsifier-free emulsion polymerization St with AA and function with dithioglycol to assemble the nanospheres, then gold nanoparticles were chemisorbed onto the thiol groups and formed monolayers on the surface of poly(St co-AA) nanospheres. Finally, horseradish peroxidase (HRP) was immobilized on the surface of the gold nanoparticles. The sensor displayed an excellent electrocatalytical response to reduction of H2O2 without the aid of an electron mediator. The biosensor showed a linear range of 8.0 micromol L(-1)-7.0 mmol L( 1) with a detection limit of 4.0 micromol L(-1). The biosensor retained more than 97.8% of its original activity after 60 days' storage. Moreover, the studied biosensor exhibited good current reproducibility and good fabrication reproducibility. PMID- 17723394 TI - Bulk-modified modified screen-printing carbon electrodes with both lactate oxidase (LOD) and horseradish peroxide (HRP) for the determination of L-lactate in flow injection analysis mode. AB - A screen-printed carbon electrode modified with both HRP and LOD (SPCE-HRP/LOD) has been developed for the determination of L-lactate concentration in real samples. The resulting SPCE-HRP/LOD was prepared in a one-step procedure, and was then optimised as an amperometric biosensor operating at [0, -100]mV versus Ag/AgCl for L-lactate determination in flow injection mode. A significant improvement in the reproducibility (coefficient variation of about 10%) of the preparation of the biosensors was obtained when graphite powder was modified with LOD in the presence of HRP previously oxidised by periodate ion (IO4-). Optimisation studies were performed by examining the effects of LOD loading, periodation step and rate of the binder on analytical performances of SPCE HRP/LOD. The sensitivity of the optimised SPCE-HRP/LOD to L-lactate was 0.84 nAL micromol(-1) in a detection range between 10 and 180 microMol. The possibility of using the developed biosensor to determine L-lactate concentrations in various dairy products was also evaluated. PMID- 17723396 TI - A selective optical sensor for picric acid assay based on photopolymerization of 3-(N-methacryloyl) amino-9-ethylcarbazole. AB - A novel optical sensor based on covalent immobilization for picric acid assay has been described. To improve the stability of the sensor, a terminal double bond was attached to the fluorescent compound, 3-amino-9-ethylcarbazole (AEC), via methacryloyl chloride. The resultant compound, 3-(N-methacryloyl) amino-9 ethylcarbazole (MAEC) was copolymerized with 2-hydroxypropyl methacrylate on surface-modified quartz glass plates by UV irradiation. The resulting optical sensor (optode membrane) was used to determine picric acid based on fluorescence quenching. It shows a linear response toward picric acid in the concentration range of 9.33 x 10(-8) to 9.33 x 10(-5) mol l(-1), with rapid response, high stability and good selectivity to picric acid. PMID- 17723395 TI - A biosensor based on graphite epoxy composite electrode for aspartame and ethanol detection. AB - A gelatin membrane with carboxyl esterase and alcohol oxidase was subsequently integrated onto the surface of a graphite epoxy composite electrode (GECE). The developed biosensors showed linearity in the range of 2.5-400 microM for aspartame and 2.5-25 microM for ethanol with response times of 170 and 70s for each analyte, respectively. The resulting bienzyme biosensor was used for aspartame detection in diet coke samples and ethanol detection in beer and wine samples. From the obtained results, it can be concluded that the developed biosensor is a selective, practical and economic tool for aspartame and ethanol detection in real samples. PMID- 17723397 TI - Potentiometric anion selectivity of polymer-membrane electrodes based on cobalt, chromium, and aluminum salens. AB - Metallo-salens of cobalt(II) (Co-Sal), chromium(III) (Cr-Sal), and aluminum(III) (Al-Sal) are used as the active ionophores within plasticized poly(vinyl chloride) membranes. It is shown that central metal-ion plays a critical role in directing the ionophore selectivity. Polymer-membrane electrodes based on Co-Sal, Cr-Sal, and Al-Sal are demonstrated to exhibit enhanced responses and selectivity toward nitrite/thiocyanate, thiocyanate, and fluoride anions, respectively. The improved anion selectivity of the three ionophore systems is shown to deviate significantly from the classical Hofmeister pattern that is based only on ion lipophilicity. For example, optimized membrane electrodes for nitrite ion based on Co-Sal exhibit logK(Nitrite,Anion)(pot) values of -5.22, -4.66, -4.48, -2.5 towards bromide, perchlorate, nitrate, and iodide anions, respectively. Optimized membrane electrodes based on Co-Sal and Cr-Sal show near-Nernstian responses towards nitrite (-57.9+/-0.9 mV/decade) and thiocyanate (-56.9+/-0.8 mV/decade), respectively, with fast response and recovery times. In contrast, Al-Sal based membrane electrodes respond to fluoride ion in a super-Nernstian (-70+/-3 mV/decade) and nearly an irreversible mode. The operative response mechanism of Co-Sal, Cr-Sal, and Al-Sal membrane electrodes is examined using the effect of added ionic sites on the potentiometric response characteristics. It is demonstrated that addition of lipophilic anionic sites to membrane electrodes based on the utilized metallo-salens enhances the selectivity towards the primary ion, while addition of cationic sites resulted in Hofmeister selectivity patterns suggesting that the operative response mechanism is of the charged carrier type. Electron spin resonance (ESR) data indicates that Co(II) metal-ion center of Co Sal ionophore undergoes oxidation to Co(III). This process leads to formation of a charged anion-carrier that is consistent with the response behavior obtained for Co-Sal based membrane electrodes. PMID- 17723399 TI - Refreshable mercury film silver based electrode for determination of chromium(VI) using catalytic adsorptive stripping voltammetry. AB - The refreshable mercury film silver based electrode Hg(Ag)FE applied for determination of Cr(VI) traces using catalytic adsorptive striping voltammetry (CAdSV) will be presented. The film electrode is characterized by its very good surface reproducibility (not less than 2%) and long-term stability (1500-2000 measurement cycles). The mechanical refreshing of mercury film is realized in the specially constructed device, in a time shorter than 1-2s. In the paper, it will be proved that a mechanically weak hanging mercury drop electrode (HMDE) may be substituted by mercury film Hg(Ag)FE electrode with a surface area adjustable from 1.5 to 12 mm2. For the electrode surface 4 mm2 the detection limit obtained for Cr(VI) was 0.19 nM, while the linearity range measured for a 20s accumulation time was between 0.5 and 50 nM. The relative standard deviation (R.S.D.) in determination of Cr(VI) varied from 1 to 5%. The influence of the excess of Cr(III) on determination of Cr(VI) was analyzed using samples from the Dobczyce reservoir spiked with known amounts of Cr(VI) and Cr(III). PMID- 17723398 TI - Measuring quaternary ammonium cleaning agents with ion selective electrodes. AB - Data for coated-wire, ion selective electrodes (ISEs) are presented for cationic surfactant ions found in common cleaners including benzyldimethyltetradecylammonium, benzyldimethyldodecylammonium, and benzyldimethylhexadecylammonium. The ion exchangers dinonylnaphthalene sulfonic acid, tetraphenyborate, and tetrakis(4-chlorophenyl)borate are examined, showing dinonylnaphthalene sulfonic acid to be the favored species. The ISEs exhibit approximately Nernstian behavior down to the 10(-6) M limit of detection with lifetimes in excess of 50 days when used continuously, and a shelf life of over 100 days. Reaching the upper detection limit at the critical micelle concentration requires use of polymeric-membrane reference electrodes including a new membrane cocktail, which allow response measurements of an order of magnitude higher than the traditional fritted-glass reference electrode. The surfactant ISEs show excellent selectivity over the common metal ions Na+, K+, Mg2+, Ca2+, and Cu2+ with selectivity coefficients less than 10(-5.3). The ISEs are also selective over the lower molecular weight quaternary ammonium ions tetradecyltrimethylammonium, dodecyltrimethylammonium, benzyldimethyl(2 hydroxyethyl)ammonium, and tetrabutylammonium with selectivity coefficients ranging from 10(-1.7) to 10(-5.5). Use of a single electrode to determine accurately the total cationic surfactant concentration in common cleaning solutions is accomplished with information about concentration dependent interferences and a modified Nikolsky-Eisenman model. Finally, quaternary ammonium surfactants have a deleterious effect on the measurements of pH and common ions like K+, Mg2+ and Ca2+ with polymeric ISEs. This makes it critical to include surfactant electrodes in a detector array when cleaning agents are present. PMID- 17723400 TI - Chemiluminescence from singlet oxygen under laminar flow condition in a micro channel. AB - Singlet oxygen was generated by reaction of sodium hypochlorite and hydrogen peroxide in a micro-channel. The two reagent solutions were delivered into the micro-channel by syringe pumps, providing a laminar flow. Such a laminar flow forms a liquid-liquid interface instantly in a micro-channel, and then the interface collapses gradually through molecular diffusion with the residence times. The chemiluminescence from the singlet oxygen was emitted in the course of the collapse of the interface under laminar flow condition. The chemiluminescence intensity was observed continuously and stably in the micro-channel as long as the reagents were fed into the channel. We examined the features of the chemiluminescence emitted in the micro-channel by changing the flow rates of reagents and the detection points in the micro-channel. The data obtained were considered along with the residence times and diffusion lengths. We also examined the effects of antioxidants, such as sodium azide, histidine, nitroblue tetrazolium, and 2-propanol on the chemiluminescence intensity. PMID- 17723401 TI - A novel electrogenerated chemiluminescence sensor for pyrogallol with core-shell luminol-doped silica nanoparticles modified electrode by the self-assembled technique. AB - The core-shell luminol-doped SiO2 nanoparticles were synthesized and immobilized on the surface of chitosan film coating graphite electrode by the self-assembled technique. Then, a novel electrogenerated chemiluminescence (ECL) sensor for pyrogallol was developed based on its ECL enhancing effect for the core-shell luminol-doped silica nanoparticles. The ECL analytical performances and the sensing mechanism of this ECL sensor for pyrogallol were investigated in detail. The corresponding results showed that: compared with the conventional ECL reaction procedures by luminol ECL reaction system, the electrochemical (EC) reaction of pyrogallol and its subsequent chemiluminescence (CL) reaction occurred in the different spatial region whilst offering a high efficiency to couple the EC with the CL reaction to form the ECL procedures. In this case, this new sensing scheme offered more potential to improve the analytical performances of the ECL reaction. Under the optimum experimental conditions, this ECL sensor showed less than 5% decrease in continuums over 100 times ECL measurements, the detection limit was 1.0 x 1.0(-9) mol/L for pyrogallol. The linear range extended from 3.0 x 10(-9) mol/L to 2.0 x 10(-5) mol/L for pyrogallol. PMID- 17723402 TI - Synthesis of water-soluble, ring-substituted squaraine dyes and their evaluation as fluorescent probes and labels. AB - A series of ring-substituted squaraines absorbing and emitting in the red and NIR spectral region was synthesized and their spectral and photophysical properties (quantum yields, fluorescence lifetimes) and photostabilities were measured and compared to Cy5, a commonly used fluorescent label. The absorption maxima in aqueous media were found to be between 628 and 667 nm and the emission maxima are between 642 and 685 nm. Squaraine dyes exhibit high extinction coefficients (163,000-265,000 M(-1) cm(-1)) and lower quantum yields (2-7%) in aqueous buffer but high quantum yields (up to 45%) and long fluorescence lifetimes (up to 3.3 ns) in presence of BSA. Dicyanomethylene- and thio-substituted squaraines exhibit an additional absorption around 400 nm with extinction coefficients between 21,500 and 44,500 M(-1) cm(-1). These dyes are excitable not only with red but also with blue diode lasers or light emitting diodes. Due to the favourable spectral and photophysical properties these dyes can be used as fluorescent probes and labels for intensity- and fluorescence lifetime-based biomedical applications. PMID- 17723403 TI - On-line dynamic fractionation and automatic determination of inorganic phosphorus in environmental solid substrates exploiting sequential injection microcolumn extraction and flow injection analysis. AB - Sequential injection microcolumn extraction (SI-MCE) based on the implementation of a soil-containing microcartridge as external reactor in a sequential injection network is, for the first time, proposed for dynamic fractionation of macronutrients in environmental solids, as exemplified by the partitioning of inorganic phosphorus in agricultural soils. The on-line fractionation method capitalises on the accurate metering and sequential exposure of the various extractants to the solid sample by application of programmable flow as precisely coordinated by a syringe pump. Three different soil phase associations for phosphorus, that is, exchangeable, Al- and Fe-bound, and Ca-bound fractions, were elucidated by accommodation in the flow manifold of the three steps of the Hieltjes-Lijklema (HL) scheme involving the use of 1.0M NH4Cl, 0.1M NaOH and 0.5M HCl, respectively, as sequential leaching reagents. The precise timing and versatility of SI for tailoring various operational extraction modes were utilized for investigating the extractability and the extent of phosphorus re distribution for variable partitioning times. Automatic spectrophotometric determination of soluble reactive phosphorus in soil extracts was performed by a flow injection (FI) analyser based on the Molybdenum Blue (MB) chemistry. The 3sigma detection limit was 0.02 mg P L(-1) while the linear dynamic range extended up to 20 mg P L(-1) regardless of the extracting media. Despite the variable chemical composition of the HL extracts, a single FI set-up was assembled with no need for either manifold re-configuration or modification of chemical composition of reagents. The mobilization of trace elements, such as Cd, often present in grazed pastures as a result of the application of phosphate fertilizers, was also explored in the HL fractions by electrothermal atomic absorption spectrometry. PMID- 17723404 TI - A novel spectrophotometric method for batch and flow injection determination of sulfite in beverages. AB - A novel spectrophotometric assay method for batch and flow injection determination of sulfite in beverages is described. The method involves a reaction with diaquacobyrinic acid heptamethyl ester (diaquacobester, DACbs) in acetate buffer of pH 3 to form a highly stable sulfite cobester complex (SO3Cbs). In the absence of sulfite, the reagent displays three absorption maxima at 349, 409 and 525 nm. Addition of sulfite is associated with the development of a new absorption band at 313 nm, an increase in the intensity of the band at 425 nm and a decrease in the absorbance of the bands at 349 and 525 nm. Variations of the absorptions at 313, 349, 425 and 525 nm are linearly proportional to sulfite concentrations over the range of 0.05-25 microg ml(-1)with a detection limit of 0.01-0.2 microg ml(-1). Negligible interferences are caused by most common ions. Validation of the method according to the quality assurance standards shows suitability for quality control assessment of sulfite in complex matrices without prior treatment. The method has the advantages of high selectivity, good sensitivity, fast reaction, high stability of the reagent and reaction product and absorbance measurements at four different wavelengths in the same run. The method is successfully applied to determine the sulfite contents of some beverages. The results compare fairly well with data obtained using the standard method. PMID- 17723405 TI - Monodisperse porous polymer particles with polyionic ligands for ion exchange separation of proteins. AB - A new "grafting to" strategy was proposed for the preparation of polymer based ion exchange supports carrying polymeric ligands in the form of weak or strong ion exchangers. Monodisperse porous poly(glycidyl methacrylate-co-ethylene dimethacrylate), poly(GMA-co-EDM) particles 5.9 microm in size were synthesized by "modified seeded polymerization". Poly(2,3-dihydroxypropyl methacrylate-co ethylene dimethacrylate), poly(DHPM-co-EDM) particles were then obtained by the acidic hydrolysis of poly(GMA-co-EDM) particles. The hydroxyl functionalized beads were treated with 3-(trimethoxysilyl)propyl methacrylate to have covalently linked methacrylate groups on the particle surface. The selected monomers carrying weak or strong ionizable groups (2-acrylamido-2-methyl-1-propane sulfonic acid, AMPS; 2-dimethylaminoethylmethacrylate, DMAEM and N-[3 (dimethylamino)propyl] methacrylamide, DMAPM) were subsequently grafted onto the particles via immobilized methacrylate groups. The final polymer based materials with polyionic ligands were tried as chromatographic packing in the separation of proteins by ion exchange chromatography. The proteins were successfully separated both in the anion and cation exchange mode with higher column yields with respect to the previously proposed materials. The plate heights obtained for poly(AMPS) and poly(DMAEM) grafted poly(DHPM-co-EDM) particles by using proteins as the analytes were 80 and 200 microm, respectively. Additionally, the plate height exhibited no significant increase with the increasing linear flow rate in the range of 1-20 cm/min. The most important property of the proposed strategy is to be applicable for the synthesis of any type of ion exchanger both in the strong and weak form. PMID- 17723406 TI - Geographical classification of wine and olive oil by means of classification and influence matrix analysis (CAIMAN). AB - Classification and influence matrix analysis (CAIMAN) is a new classification method, recently proposed and based on the influence matrix (also called leverage matrix). Depending on the purposes of the classification analysis, CAIMAN can be used in three outlines: (1) D-CAIMAN is a discriminant classification method, (2) M-CAIMAN is a class modelling method allowing a sample to be classified, not classified at all, or assigned to more than one class (confused) and (3) A-CAIMAN deals with the asymmetric case, where only a reference class needs to be modelled. In this work, the geographic classification of samples of wine and olive oil has been carried out by means of CAIMAN and its results compared with discriminant analysis, by focusing great attention on the model predictive capabilities. The geographic characterization has been carried out on three different datasets: extra virgin olive oils produced in a small area, with a "protected denomination of origin" label, wines with different denominations of origin, but produced in enclosed geographical areas, and olive oils belonging to different production areas. Final results seem to indicate that the application of CAIMAN to the geographical origin identification offers several advantages: first, it shows--on an average basis--good performances; second, it is able to deal in a simple way classification problems related to tipicity, authenticity, and uniqueness characterization, which are of increasing interest in food quality issues. PMID- 17723407 TI - On-line monitoring of microg/L levels of haloacetic acids using ion chromatography with post-column nicotinamide reaction and fluorescence detection. AB - A method for measuring the concentrations of the five regulated haloacetic acids (HAA5) in drinking water is reported. This method uses ion chromatography to separate HAA5 species, followed by post-column reaction with nicotinamide and detection of the fluorescent products. The result of method detection limit, accuracy, precision, linearity and interference studies are reported. The on-line monitoring method is compared directly to USEPA 552.3 in Memphis drinking water. Though not meant to replace the USEPA 552.3 for compliance monitoring, the proposed method does offer attractive alternatives considering the ease of automation and application of on-line monitoring directly from drinking water distribution systems. PMID- 17723408 TI - Determination of selectivity differences for basic compounds in gradient reverse phase high performance liquid chromatography under high pH conditions by partial least squares modelling. AB - The retention behaviour of compounds in a chromatographic system is believed to be multivariate by nature, i.e. many physico-chemical properties of an analyte can influence its retention. Principal component analysis (PCA) and partial least squares (PLS) can therefore be particularly useful tools for visualising, exploring and modelling the complex interactions between solutes and the mobile and stationary phase. PCA allows the relationships between compounds (the observations) and their retention parameters (the variables) to be visualised in usually just two or three dimensions. PLS can be used to model quantitative structure-retention relationships (QSRRs) and may lead to better understanding of retention and selectivity changes in chromatographic systems. The objective of the study was to investigate the chromatographic behaviour of basic compounds under optimised gradient conditions using octadecyl high performance liquid chromatography (HPLC) columns designed for high pH separations. Three pharmaceutical mixtures were analysed by linear gradient reverse phase HPLC (RP HPLC) at high pH using ammonia as a pH modifier, and methanol and/or acetonitrile as the organic modifier. The separations were carried out on three octadecyl columns: Waters XTerra MS C18, Agilent Zorbax Extend C18 and Thermo Hypersil Keystone BetaBasic-18. Multivariate PCA and PLS modelling were employed to explore and explain the differences in selectivity between the chromatographic systems studied when the basic compounds were analysed under the high pH conditions. The interactions between the analytes and the mobile-stationary phases were described by relating the compound molecular descriptors with the selectivity of each chromatographic system. The selectivity differences between the chromatographic systems were identified. PMID- 17723409 TI - Determination of lanthanides by source excited energy dispersive X-ray fluorescence (EDXRF) method after preconcentration with ammonium pyrrolidine dithiocarbamate (APDC). AB - A new analytical procedure for determination of lanthanides in environmental samples after chemical separation from major matrix elements on DOWEX 50W-X8 resin followed by preconcentration with chelating agent ammonium pyrrolidine dithiocarbamate (APDC) and analyses of thin targets by energy dispersive X-ray fluorescence (EDXRF) method using 109Cd as the source of excitation was presented. Characteristic Lalpha X-ray lines of the lanthanides were used for calculations of the net peak area and mass concentrations. The influence of pH value of the solution and addition of organic matter on the complexation was investigated. Percentage of recovery of each lanthanide after separation on DOWEX 50W-X8 resin was also determined. Accuracy of the method was tested on standard reference materials and real environmental samples (red mud material). For that purpose samples of standard reference materials and red mud were prepared as thick targets and directly analyzed (without the separation step) by EDXRF method using 241Am as the excitation source. In that case lanthanides concentrations were determined over their characteristic Kalpha X-ray lines and results were compared with those obtained after separation/preconcentration step described above. Results showed that selected lanthanides made stable complexes with APDC in the alkaline medium with the maximum recovery at pH=8. The presence of organic matter slightly modified the complexation by means of somewhat higher recovery percentage at pH lower than 7 and approx. 20% lower recovery at pH higher than 7. Recovery of the elements after separation on DOWEX 50W-X8 resin and preconcentration with APDC at pH=8 varied from 91.4% (Pr) to only 24.9% in the case of Dy. Concentrations of lanthanides measured in standard reference material and environmental samples of red mud after microwave digestion, separation on DOWEX 50W-X8 resin, preconcentration with APDC at pH=8 and recalculation on the percentage of recovery were in good agreement with certified values in the case of SRM as well as with the concentrations obtained by direct determination over Kalpha lines using 241Am excitation source in the case of red mud leading to the conclusion that presented method was applicable for the determination of lanthanides in real environmental samples. PMID- 17723410 TI - Digital image-based titrations. AB - The exploitation of digital images obtained from a CCD camera (WebCam) as a novel instrumental detection technique for titration is proposed for the first time. Named of digital image-based (DIB) titration, it also requires, as a traditional titration (for example, spectrophotometric, potentiometric, conductimetric), a discontinuity in titration curves where there is an end point, which is associated to the chemical equivalence condition. The monitored signal in the DIB titration is a RGB-based value that is calculated, for each digital image, by using a proposed procedure based on the red, green, and blue colour system. The DIB titration was applied to determine HCl and H3PO4 in aqueous solutions and total alkalinity in mineral and tap waters. Its results were compared to the spectrophotometric (SPEC) titration and, by applying the paired t-test, no statistic difference between the results of both methods was verified at the 95% confidence level. Identical standard deviations were obtained by both titrations in the determinations of HCl and H3PO4, with a slightly better precision for DIB titration in the determinations of total alkalinity. The DIB titration shows to be an efficient and promising tool for quantitative chemical analysis and, as it employs an inexpensive device (WebCam) as analytical detector, it offers an economically viable alternative to titrations that need instrumental detection. PMID- 17723411 TI - Optimization of LC-MS/MS using triple quadrupole mass analyzer for the simultaneous analysis of carbosulfan and its main metabolites in oranges. AB - This paper describes an analytical method involving a simple solvent extraction for the simultaneous liquid chromatography coupled to quadrupole tandem mass spectrometry (LC-MS/MS) determination of carbosulfan, its most toxic metabolite- carbofuran--, and its other main metabolites--3-hydroxycarbofuran, 3 ketocarbofuran, 3-hydroxy-7-phenolcarbofuran, 3-keto-7-phenolcarbofuran, 7 phenolcarbofuran and dibutylamine--in oranges. Chromatography was performed on a Zorbax Bonus-RP (150 mm x 2.1 mm, 5 microm). The mobile phase was a ternary gradient water-methanol-acetonitrile with 1.0 mM ammonium acetate at flow rate of 0.2 ml min(-1). The LC separation and MS/MS optimization were studied to select the most appropriate operating conditions. The method developed has also been validated. The limits of quantification (LOQs) were from 1 microg kg(-1) for carbofuran to 10 microg kg(-1) for 3-keto-7-phenolcarbofuran. Extracts spiked with carbosulfan and its metabolites, at LOQ level, yielded average recoveries in the range 60-94%, with relative standard deviations (R.S.D.s) less than 15%. Calibration curves for carbosulfan and its metabolites (range LOQ-1000LOQ) were linear, with coefficients of correlations better than 0.990. The method was successfully applied to establish the primary degradation products in oranges treated with carbosulfan. The LC-MS/MS method developed is simple, rapid, and suitable for the quantification and confirmation of carbosulfan and seven of its main metabolites in orange at levels lower than 10 microg kg(-1). PMID- 17723412 TI - Measurement of tobramycin by reversed-phase high-performance liquid chromatography with mass spectrometry detection. AB - Analysis of tobramycin faces challenges owing to its significant basicity, hydrophilicity and lack of a UV absorbing chromophore. Chromatographic methods, coupled with derivatization to introduce chromophores for tobramycin analysis, were extensively studied. A direct reversed-phase HPLC method for tobramycin analysis has not been reported. Here, we would like to report a simple LC/MS method for quantitative analysis of tobramycin in pharmaceutical formulations. Reversed-phase HPLC analysis of tobramycin was achieved using a pH stable C18 column with basic (pH 11) aqueous mobile phase (ammonium hydroxide buffer), while direct detection was carried out employing a single quadruple mass detector in negative mode via electrospray ionization. This unique separation-detection combination provided simple and specific determination of tobramycin. This method was found to be linear at a tobramycin concentration range of 0.2-0.8 mg/mL with a correlation coefficient value of 0.999. The quantitation limit and detection limit were calculated as 0.210 and 0.063 microg/mL, respectively, with 99.994% confidence. This method was successfully applied to measure tobramycin content in matrices containing tobramycin and other pharmaceutical formulation ingredients. Recoveries of 101.8, 97.8 and 106.7% were obtained for tobramycin spiked in the pharmaceutical formulation at concentrations of 1.68, 1.0 and 0.35 mg/mL, respectively. The relative standard deviations for six injections of spiked samples ranged from 0.2 to 3.2%, indicating good method repeatability. PMID- 17723413 TI - Simultaneous analysis of trans- and cis-isomers of 2-glucosyloxycinnamic acids and coumarin derivatives in Dendrobium thyrsiflorum by high-performance liquid chromatography (HPLC)-photodiode array detection (DAD)-electrospray ionization (ESI)-tandem mass spectrometry (MS). AB - A novel method has been developed for simultaneous analysis for three pairs of trans- and cis-isomers of 2-glucosyloxycinnamic acids, along with their biogenic metabolites (three coumarin derivatives including scopoletin, scoparone and ayapin) in a Chinese medicinal herb Dendrobium thyrsiflorum by using high performance liquid chromatography (HPLC)-photodiode array detection (DAD) electrospray ionization (ESI)-tandem mass spectrometry (MS). The method was carried out by using a Polaris C18 column with a gradient solvent system of 0.5% acetic acid aqueous solution-acetonitrile. Seven target analytes including isodensifloside, isothyrsifloside, densifloside, thyrsifloside, scoparone, ayapin and scopoletin were exclusively identified by comparing their retention behaviors, UV and MS spectra with the authentic standards, and their contents in D. thyrsiflorum were simultaneous determined by employing UV detection at 342 nm. In addition, another pair of isomers of 2-glucosyloxycinnamic acids was putatively elucidated mainly based on the MS fragmentation. The method was validated and found to be satisfactorily linear, selective and robust. Recoveries ranged from 95.56 to 97.94% for all compounds at three different spiking levels. The limits of detection (LOD) and quantitation (LOQ) ranged, respectively, from 0.02 to 0.13 microg mL(-1) and 0.07 to 0.39 microg mL(-1) depending on various compounds. The established quality evaluation method was successfully used for evaluating the quality of D. thyrsiflorum samples of different organs and collections. PMID- 17723414 TI - The automation of the acquisition and evaluation of pyrolysis-gas chromatography mass spectrometry data for paint samples. AB - The evaluation is described of an automated pyrolysis-gas chromatography-mass spectrometry system combined with a software package to convert total ion current chromatograms into forms that resemble a conventional mass spectra called "spectragrams". The spectragram for a single paint sample can be "closest fit" matched to a previously created paint pyrogram library via pre-determined target compounds in a handling list. Up to 45 paint samples can be dealt with in an overnight unattended run. PMID- 17723415 TI - Monitoring yoctomole alkaline phosphatase by capillary electrophoresis with on capillary catalysis-electrochemical detection. AB - An electrophoretically mediated microanalysis method for detection of yoctomole (ymol) alkaline phosphatase (ALP) was developed by a combination of on-capillary enzyme-catalyzed reaction and electrochemical detection. In this method, ALP molecules were electrokinetically injected into a capillary of 10 microm i.d. and then electromigrated to the section of the capillary immersed in a warm water bath of 37 degrees C, where ALP reacted for a certain time with disodium phenyl phosphate as the enzyme substrate. ALP could be measured through determining the electroactive product phenol of the enzyme-catalyzed reaction by using electrochemical detection. The phenol concentration was proportional to the mass of ALP. As a catalyst, ALP was not consumed during the reaction, which provided amplification of signal with prolonged the reaction time. In order to enhance the signal-to-noise ratio, the detection end of the capillary was etched to a horn shape and a single carbon fiber microcylinder electrode of 6 microm in diameter as the working electrode was inserted into the detection end of the capillary. Under these conditions, the mass of ALP as low as 1.2 x 10(-22) mol (72 molecules) or 4.0 x 10(-23) mol (24 molecules) could be detected for the on capillary reaction time of 15 min or 2h. PMID- 17723416 TI - Enhancing deoxyribonucleic acid (DNA) detection sensitivity through microconcentration on patterned fluorocarbon polymer surface. AB - A microconcentration concept is proposed to enhance the sensitivity of deoxyribonucleic acid (DNA) hybridization due to evaporation of the hybridization solution on a patterned hydrophobic fluorocarbon polymer (FCP) surface. The combination of microconcentration and hybridization processes provides a tool to manipulate nanoliter solution. To fabricate a patterned DNA microarray with hydrophobic surrounding surface, a plasma polymerization and lift-off protocol was designed so that the process can be carried out in a standard microelectronic fabrication laboratory with minimal adjustments on the equipment. After microconcentration, a 1 microL hybridization solution can be concentrated to below 10 nL, which improves the hybridization sensitivity by a factor of 100. PMID- 17723417 TI - Solid phase microextraction and gas chromatography with ion trap detector (GC ITD) analysis of amitraz residues in beeswax after hydrolysis to 2,4 dimethylaniline. AB - An analytical method for the determination of amitraz residues in beeswax after hydrolysis to 2,4-dimethylaniline is reported. It consists of wax extraction with an acid buffer solution, head space solid phase microextraction and GC-ITD analysis. The limit of determination is 1 ng g(-1). Wax samples from beekepers and commercial foundations were analysed, content of residues varied from <1 to 20.5 ng g(-1). PMID- 17723418 TI - Silicone glue coated stainless steel wire for solid phase microextraction. AB - A new solid phase microextraction (SPME) fiber based on high-temperature silicone glue coated on a stainless steel wire is presented. The fiber coating can be prepared easily in a few minutes, it is mechanically stable and exhibits relatively high thermal stability (up to 260 degrees C). The extraction properties of the fiber to benzene, toluene, ethylbenzene, and xylenes (BTEX) were examined using both direct and headspace SPME modes coupled to gas chromatography-flame ionization detection. The effects of the extraction and desorption parameters including extraction and desorption time, sampling and desorption temperature, and ionic strength on the extraction/desorption efficiency have been studied. For both headspace and direct SPME the calibration graphs were linear in the concentration range from 0.5 microg L(-1) to 10 mg L( 1) (R2>0.996) and detection limits ranged from 0.07 to 0.24 microg L(-1). Single fiber repeatability and fiber-to-fiber reproducibility were less than 6.8 and 21.5%, respectively. Finally, headspace SPME was applied to determine BTEX in petrol station waste waters with spiked recoveries in the range of 89.7-105.2%. PMID- 17723419 TI - Microwave assisted micellar extraction coupled with solid phase microextraction for the determination of organochlorine pesticides in soil samples. AB - Microwave assisted micellar extraction (MAME) coupled with solid phase microextraction (SPME) and HPLC-UV determination have been used for the determination of five organochlorine pesticides from agricultural soil samples. A non-ionic surfactant, Polyoxyethlylene 10 Lauryl Ether was used, and the different variables for the optimization of MAME and SPME procedures were studied. This method was applied successfully to the determination of these pesticides in several kinds of agricultural soil samples with different characteristics. Most of the compounds studied can be recovered in good yields with R.S.D. lower than 9% and detection limit ranged between 56-96 ng g(-1) for the pesticides studied. PMID- 17723420 TI - A new analytical application of nylon-induced room-temperature phosphorescence: determination of thiabendazole in water samples. AB - This paper discusses the first analytical determination of the widely used fungicide thiabendazole by nylon-induced phosphorimetry. Nylon was investigated as a novel solid-matrix for inducing room-temperature phosphorescence of thiabendazole, which was enhanced under the effect of external heavy-atom salts. Among the investigated salts, lead(II) acetate was the most effective in yielding a high phosphorescence signal. An additional enhancement of the phosphorescence emission was attained when the measurements were carried out under a nitrogen atmosphere. There was only a moderate increase in the presence of cyclodextrins. The room-temperature phosphorescence lifetimes of the adsorbed thiabendazole were measured under different working conditions and, in all cases, two decaying components were detected. On the basis of the obtained results, a very simple and sensitive phosphorimetric method for the determination of thiabendazole was established. The analytical figures of merit obtained under the best experimental conditions were: linear calibration range from 0.031 to 0.26 microg ml(-1) (the lowest value corresponds to the quantitation limit), relative standard deviation, 2.4% (n=5) at a level of 0.096 microg ml(-1), and limit of detection calculated according to 1995 IUPAC Recommendations equal to 0.010 microg ml(-1) (0.03 ng/spot). The potential interference from common agrochemicals was also studied. The feasibility of determining thiabendazole in real samples was successfully evaluated through the analysis of spiked river, tap and mineral water samples. PMID- 17723421 TI - Automated flow fluorescent immunoassay for part per trillion detection of the neonicotinoid insecticide thiamethoxam. AB - An ultra sensitive automated flow fluorescent immunoassay was developed using the KinExAtrade mark 3000 system for quantitative analysis of the neonicotinoid insecticide thiamethoxam. Five new monoclonal antibodies were obtained and screened with a competitive ELISA. One monoclonal antibody designated as E6VI was evaluated for sensitivity, selectivity and solvent tolerance with the KinExA. Sensitivity determined from the concentration of half-maximal inhibition (IC50) was obtained by plotting KinExA signals to a four-parameter sigmoidal curve as a function of analyte concentrations. For the most sensitive clone, the IC50 and the limit of detection were approximately 30 pg ml(-1) and 16 pg ml(-1), respectively. Cross-reactivity was estimated by measuring the equilibrium constants (K(d)) for four other neonicotinoid insecticides (clothianidin, imidacloprid, dinotefuran, and acetamiprid). E6VI was very specific to thiamethoxam with <0.11% cross-reactivity for tested neonicotinoids. An excellent correlation (r2=0.99) was obtained between spiked and measured concentrations of thiamethoxam in stream and tap water, potato, cucumber, and apple samples. PMID- 17723422 TI - Ultrasensitive detection of pepsinogen I and pepsinogen II by a time-resolved fluoroimmunoassay and its preliminary clinical applications. AB - A fast and highly sensitive assay for pepsinogen I (PG I) and pepsinogen II (PG II) by using time-resolved fluoroimmunoassay (TRFIA) detection technique has been developed for the determination of serum PG I and PG II against gastrointestinal diseases. On the noncompetitive assay, one monoclonal antibody (McAb) coated on wells was directed against a specific antigenic site on the PG I or PG II. The McAb, called as labelling McAb, was prepared with the europium-chelate of N-(p isothiocyanatobenzyl)-diethylenetriamine-N,N,N,N-tetraacetic acid and directed against a different antigenic site on the PG I or PG II molecule. After bound/free separation by washing, the fluorescence counts of bound Eu(3+)-McAb were measured. The levels of PG in sera from patients or healthy volunteers were determined by PG I and PG II TRFIA using the autoDELFIA(1235) system. The measurement ranges of PG I-TRFIA were 3.5-328.0 microg L(-1) and those of PG II TRFIA were 2.0-55.0 microg L(-1). The within-run and between-run CVs of the PG I TRFIA were 1.9% and 4.7%, respectively, and those of PG II-TRFIA were 2.1% and 3.8%, respectively. The recovery rates of PG I-TRFIA and PG II-TRFIA were 102.7% and 104.6%, respectively. The detection limitations of PG I and PG II were 0.05 microg L(-1) and 0.02 microg L(-1), respectively. The dilution experiments showed the percentage of expected value of PG I-TRFIA was 93.2-102.3% and of PG II-TRFIA was 97.3-110.6%. The cross-reacting rate between PG I and PG II was negligible. The linear correlation of radioimmunoassay (RIA) and TRFIA measurements resulted in a correlation coefficient as 0.926 of PG I and as 0.959 of PG II. The europium labelling McAbs were stable for at least one year at -20 degrees C, and the results of the TRFIA with same reagents were reproducible over one year as well. The means of 1600 healthy volunteers were 162.4+/-52.1 microg L(-1) for serum PG I, 11.7+/-6.8 microg L(-1) for serum PG II, and 13.8+/-7.4 for the PG I/PG II ratio. The normal ranges of Serum PG I levels for healthy volunteers were 58.2 266.6 microg L(-1), and those of serum PG II levels were less than 25.3 microg L( 1). The availability of a highly sensitive, reliable, and convenient PG-TRFIA method for quantifying PG will allow investigations into the possible diagnostic value of this analysis in various clinical conditions, including gastric carcinoma, duodenal ulcer, gastric ulcer and gastritis. The sensitivity and reproducibility of the assay were satisfactory for clinical applications. PMID- 17723423 TI - Comparison between conventional indirect competitive enzyme-linked immunosorbent assay (icELISA) and simplified icELISA for small molecules. AB - A simplified indirect competitive enzyme-linked immunosorbent assay (icELISA) for small molecules was established by modifying the procedure of conventional icELISA. The key change was that the analyte, antibody, and enzyme-labeled second antibody in the simplified icELISA were added in one step, whereas in conventional icELISA these reagents were added in two separate steps. Three small chemicals, namely zeatin riboside, glycyrrhetinic acid, and chlorimuron-ethyl, were used to verify the new assay format and compare the results obtained from conventional icELISA and simplified icELISA. The results indicated that, under optimized conditions, the new assay offered several advantages over the conventional icELISA, which are simpler, less time consuming and higher sensitive although it requires more amount of reagents. The assay sensitivity (IC50) was improved for 1.2-1.4-fold. Four licorice roots samples were analyzed by conventional icELISA and simplified icELISA, as well as liquid chromatography (LC). There was no significant difference among the content obtained from the three methods for each sample. The correlation between data obtained from conventional icELISA and simplified icELISA analyses was 0.9888. The results suggest that the simplified icELISA be useful for high throughput screening of small molecules. PMID- 17723424 TI - Advantages of using a mercury coated, micro-wire, electrode in adsorptive cathodic stripping voltammetry. AB - A mercury coated, gold, micro-wire electrode is used here for the determination of iron in seawater by catalytic cathodic stripping voltammetry (CSV) with a limit of detection of 0.1 nM Fe at a 60s adsorption time. It was found that the electrode surface is stable for extended periods of analyses (at least five days) and that it is reactivated by briefly (2s) applying a negative potential prior to each scan. Advantages of this electrode over mercury drop electrodes are that metallic mercury use is eliminated and that it can be readily used for flow analysis. This is demonstrated here by the determination of iron in seawater by continuous flow analysis. It is likely that this method can be extended to other elements. Experiments using bismuth coated, carbon fibre, electrodes showed that the bismuth catalyses the oxidation of the important oxidants bromate and hydrogen peroxide, which makes it impossible to use bismuth based electrodes for catalytic CSV involving these oxidants. For this reason mercury coated electrodes retain a major advantage for catalytic voltammetric analyses. PMID- 17723425 TI - Fast ultrasound-assisted treatment of urine samples for chronopotentiometric stripping determination of mercury at gold film electrodes. AB - This work describes an efficient, fast, and reliable analytical methodology for mercury determination in urine samples using stripping chronopotentiometry at gold film electrodes. The samples were sonicated in the presence of concentrated HC1 and H2O2 for 15 min in order to disrupt the organic ligands and release the mercury. Thirty samples can be treated over the optimized region of the ultrasonic bath. This sample preparation was enough to allow the accurate stripping chronopotentiometric determination of mercury in the treated samples. No background currents and no passivation of the gold film electrode due to the sample matrix were verified. The samples were also analyzed by cold vapour atomic absorption spectrometry (CV-AAS) and good agreement between the results was verified. The analysis of NIST SRM 2670 (Toxic Metals in Freeze-Dried Urine) also validated the proposed electroanalytical method. Finally, this method was applied for mercury evaluation in urine of workers exposed to hospital waste incinerators. PMID- 17723426 TI - Application of adsorptive stripping voltammetry to the simultaneous determination of bismuth and copper in the presence of nuclear fast red. AB - A sensitive and selective method for the simultaneous determination of copper and bismuth by adsorptive stripping was developed using nuclear fast red (2 anthracenesulfonic acid, 4-amino-9,10-dihydro-1,3-dihydroxy-9,10-dioxo-, monosodium salt) as selective complexing agent onto hanging mercury drop electrode. In a single scan both metals gave peaks that were distinctly separated by 85 mV allowing their determination in the presence of each other. Optimal analytical conditions were found to be: nuclear fast red concentration of 80 microM, pH of 2.8 and adsorptive potential of -300 mV versus Ag/AgCl. With accumulation time of 180s the peaks currents are proportional to concentration of copper and bismuth over the 1-100 and 5-60 ng mL(-1) range with detection limits of 0.2 and 1.2 ng mL(-1), respectively. The procedure was applied to simultaneous determination of copper and bismuth in some real samples. PMID- 17723427 TI - Influence of the physical properties and handling of silica gel modified carbon paste electrodes on the phase transfer of solved Cu(II) ions. AB - Carbon paste electrodes (CPE) modified with natural minerals might be utilised to mimic adsorption/desorption reactions at natural interfaces. As a step towards this aim, several properties and application conditions of CPEs, modified with silica gel, were tested for their influence on phase transfer reactions of solved Cu(II)-tetrammine complex ions. The peak current recorded during the anodic stripping of adsorbed Cu(II) species increased with increasing diameter of the circular electrode surface. A silica gel content of 29 mass percent yielded the highest peak current at otherwise constant exposition conditions. A substitution of graphite by glassy carbon did not enhance the electrode sensitivity. The peak current increased with increasing exposition time (up to 20 min) and with decreasing size of the modifier particles. Typically between 12% and 22% of the solved Cu ions were adsorbed onto the electrode surface and between 15% and 20% of this Cu fraction was subsequently removed by stripping and electrode regeneration. Despite the incomplete electrode regeneration the mass transfer ratios of the Cu(II) species were relatively constant during several application cycles. PMID- 17723428 TI - Application of band-target entropy minimization (BTEM) and residual spectral analysis to in situ reflection-absorption infrared spectroscopy (RAIRS) data from surface chemistry studies. AB - The band-target entropy minimization (BTEM) curve resolution technique has been used to analyze in situ reflection-absorption infrared spectroscopy (RAIRS) data of CO chemisorption on Ni(111) single crystal surfaces. The bilinearity assumption for pRAIRS data, that is, negative logarithm to the base 10 of raw reflectance RAIRS data, was found to be sufficiently valid for the test data. A total of 11 real pure component pRAIRS spectra were elucidated via BTEM in tandem with an iterative residual spectral data analysis. Furthermore, 2 abstract pure component right singular vectors were found to account for all the pRAIRS non linearities, baseline drifts and other spectral noise. In total, 100.2% of the pRAIRS signals were accounted for by these 13 spectral components. The 11 real pure component pRAIRS spectra and their corresponding relative concentration kinetic sequences correlate with 6 well-known adsorbed CO domain structures. Moreover, amongst the BTEM resolved spectra were five new bands that were not previously observed using conventional visual identification methods adopted by surface chemists. These new bands engendered new understanding to the mechanism of CO chemisorption on Ni(111). The combination of BTEM with residual spectral analysis was thus demonstrated to be efficacious for curve resolution of in situ RAIRS data obtained from surface chemistry studies. PMID- 17723429 TI - Investigation of degradation mechanisms by portable Raman spectroscopy and thermodynamic speciation: the wall painting of Santa Maria de Lemoniz (Basque Country, North of Spain). AB - This article presents the "in situ" and totally non destructive investigation of a wall painting in Santa Maria de Lemoniz (Biscay, Basque Country, Spain) by Raman microprobe spectroscopy 14 years after its restoration. Although no sample was allowed to be taken, it has been possible to determine the original pigments in the artwork (vermilion, red iron oxide, yellow iron oxide, carbon black, lead white), as well as some degradation products (calcium oxalate dihydrate, anhydrite). For the first time, the mechanism for the transformation of malachite into copper basic sulphates has been ascertained by the integration of Raman data with thermodynamic speciation studies. Moreover, some remarks regarding the unsuitability of the past intervention procedure with regard to the chemical stability of the artwork are made. PMID- 17723430 TI - Chromium speciation using sequential injection analysis and multivariate curve resolution. AB - In this paper we develop a suitable method for the speciation of chromium in tanning and environmental water samples. We use sequential injection analysis (SIA) with a diode array detector linked to chemometric tools such as multivariate curve resolution-alternating least squares (MCR-ALS) to determine Cr(III) and Cr(VI) species. Although Cr(III) is an absorbent species, its sensitivity is much lower than that of Cr(VI). To increase its sensitivity, therefore, it was complexed with EDTA. This method involves generating a pH gradient in the system reactor that converts dichromate into chromate in such a way that, when the sample reaches the detector, selective areas are observed and a data matrix is obtained. Applying MCR enables Cr(III) and Cr(VI) to be successfully determined simultaneously in tanning and environmental wastewater samples. PMID- 17723431 TI - Evaluation of a tungsten coil atomization-laser-induced fluorescence detection approach for trace elemental analysis. AB - The analytical utility of a tungsten (W)-coil atomization-laser-induced fluorescence (LIF) approach has been evaluated for trace level measurements of elemental chromium (Cr), arsenic (As), selenium (Se), antimony (Sb), lead (Pb), tin (Sn), copper (Cu), thallium (Tl), indium (In), cadmium (Cd), zinc (Zn) and mercury (Hg). Measurements of As, Cr, In, Se, Sb, Pb, Tl, and Sn were performed by laser-induced fluorescence using a single dye laser operating near 460 nm whose output was converted by frequency doubling and stimulated Raman scattering to wavelengths ranging from 196 to 286 nm for atomic excitation. Absolute limits of detection (LODs) of 1, 0.3, 0.3, 0.2, 1, 6, 1, 0.2 and 0.8 pg and concentration LODs of 100, 30, 30, 20, 100, 600, 100, 20, and 80 pg/mL were achieved for As, Se, Sb, Sn, In, Cu, Cr, Pb and Tl, respectively. Determinations of Hg, Pb, Zn and Cd were performed using two-color excitation approaches and resulted in absolute LODs of 2, 30, 5 and 0.6 pg, respectively, and concentration LODs of 200, 3000, 500 and 60 pg/mL, respectively. The sensitivities achieved by the W-coil LIF approaches compare well with those reported by W-coil atomic absorption spectrometry, graphite furnace atomic absorption spectrometry, and graphite furnace electrothermal atomization-LIF approaches. The accuracy of the approach was verified through the analysis of a multielement reference solution containing Sb, Pb and Tl which each had certified performance acceptance limits of 19.6-20.4 microg/mL. The determined concentrations were 20.05+/-2.60, 20.70+/ 2.27 and 20.60+/-2.46 microg/mL, for Sb, Pb and Tl, respectively. The results demonstrate that W-coil LIF provides good analytical performance for trace analyses due to its high sensitivity, linearity, and capability to measure multiple elements using a single tunable laser and suggest that the development of portable W-coil LIF instrumentation using compact, solid-state lasers is feasible. PMID- 17723432 TI - Solid sampling-graphite furnace atomic absorption spectrometry for the direct determination of silver at trace and ultratrace levels. AB - In this work, the possibilities of solid sampling-graphite furnace atomic absorption spectrometry for the direct determination of silver in solid samples of very different nature (a biological sample, a soil, an ore concentrate and a polymer) and showing substantial differences in their analyte content (from approximately, 40 ng g(-1) up to 350 microg g(-1)) have been evaluated, the goal always being to develop fast methods, only relying on the use of aqueous standards for calibration. Different factors had to be taken into account in order to develop suitable procedures for all the samples under investigation. Among the most important ones, the following can be mentioned: (i) optimization of the temperature program in order to selectively atomize the analyte; (ii) the use of chemical modifiers (such as Pd or HNO3), depending on the sample characteristics; (iii) appropriate wavelength, argon flow and sample mass selection (depending on the analyte content); (iv) the use of 3-field mode Zeeman effect background correction in order to further expand the linear range up to 1000 ng of Ag, which was needed for analysis of the sample showing the highest Ag content (polypropylene). The procedures finally proposed show interesting features for the determination of silver in solid samples: the advantage of using aqueous standard solutions for calibration, a high sample throughput (approximately, 15 min per sample), a low detection limit (2 ng g(-1)), sufficient precision (R.S.D. values in the vicinity of 10%) and a reduced risk of analyte losses and contamination. PMID- 17723433 TI - Improved sensitivity for some [corrected] metal ions by use of sulfide in the Belousov-Zhabotinskii oscillating reaction. AB - A highly sensitive method for the determination of trace amounts of some [corrected] metal ions by use of sulfide in the Belousov-Zhabotinskii (B-Z) oscillating chemical reaction is proposed. The use of sulfide increased strongly the sensitivity of the B-Z reaction for some [corrected] metal ions, such as Ag+, Pb2+, Hg2+, Cd2+, Cu2+, and Bi3+. Results showed that the variational ratio of oscillating period (P(R)) is linearly proportional to the negative logarithm of concentration of metal ions. The detection limit is down to 10(-12) mol L(-1). Various influencing factors on the determination were also examined. PMID- 17723434 TI - The potential of mid infrared spectroscopy (MIRS) for real time bioprocess monitoring. AB - The need for effective bioprocess (fermentation) monitoring is growing in importance due to the rapid pace of change in the fermentation industry, and attendant financial pressures. Vibrational spectroscopy has shown great promise in bioprocess monitoring. In particular, recently attention has been focused on the capability of mid infrared spectroscopy (MIRS) to monitor multiple analytes in highly complex fermentation fluids. The potential of this powerful analytical technique is critically evaluated by discussion of relevant studies. The advantages and limitations of MIR are discussed in the context of "rival" technologies, such as near infrared, focusing especially on employing such techniques in bioprocesses for real time (either in situ or ex situ) measurements. The potential barriers to the development of MIRS for real time monitoring are identified and further research directions highlighted. PMID- 17723435 TI - Combination of mid- and near-infrared spectroscopy for the determination of the quality properties of beers. AB - The combination of infrared (MIR) and near-infrared (NIR) spectroscopy has been employed for the determination of important quality parameters of beers, such as original and real extract and alcohol content. A population of 43 samples obtained from the Spanish market and including different types of beer, was evaluated. For each technique, spectra were obtained in triplicate. In the case of NIR a 1mm pathlength quartz flow cell was used, whereas attenuated total reflectance measurements were used in MIR. Cluster hierarchical analysis was employed to select calibration and validation data sets. The calibration set was composed of 15 samples, thus leaving 28 for validation. A critical evaluation of the prediction capability of multivariate methods established from the combination of NIR and MIR spectra was made. Partial least squares (PLS) and artificial neural networks (ANN) were evaluated for the treatment of data obtained in each individual technique and the combination of both. Different parameters of each methodology were optimized. A slightly better predictive performance was obtained for NIR-MIR combined spectra, and in all the cases ANN performs better than PLS, which may be interpreted from the existence of some non linearity in the data. The root-mean-sqare-error of prediction (RMSEP) values obtained for the combined NIR-MIR spectra for the determination of real extract, original extract and ethanol were 0.076% w/w, 0.14% w/w and 0.091% v/v. PMID- 17723436 TI - Fluorescent investigation of the interactions between N-(p-chlorophenyl)-N'-(1 naphthyl) thiourea and serum albumin: synchronous fluorescence determination of serum albumin. AB - The interactions between N-(p-chlorophenyl)-N'-(1-naphthyl) thiourea and serum albumin were investigated by fluorescence spectroscopy and UV absorption spectrum under physiological conditions. The results of spectroscopic measurements suggested that N-(p-chlorophenyl)-N'-(1-naphthyl) thiourea should have a strong ability to quench the intrinsic fluorescence of both bovine serum albumin and human serum albumin through static quenching procedure, and the hydrophobic interaction was the predominant intermolecular force stabilizing the complex. Thermodynamic parameter enthalpy changes (DeltaH) and entropy changes (DeltaS) were calculated according to the Vant'Hoff equation. The binding distances between N-(p-chlorophenyl)-N'-(1-naphthyl) thiourea and the proteins were evaluated on the basis of the theory of Foster energy transfer. In addition, the effects of other ions on the binding constants of complexes were also discussed. Synchronous fluorescence technology was successfully applied to the determination of serum albumins added to the CPNT solution. PMID- 17723437 TI - Flow injection analysis of ultratrace orthophosphate in seawater with solid-phase enrichment and luminol chemiluminescence detection. AB - Solid-phase extraction technique had been applied to extract molybdophosphoric heteropoly acid (MoP) paired with cetyltrimethylammonium bromide (CTAB) from seawater matrix using C18 sorbent. Chemiluminescence emission could be generated via MoP reaction with alkaline luminol. Based on these, a novel on-line solid phase extraction method coupled with flow injection (FI) analysis and luminol chemiluminescence detection had been established to determine ultratrace orthophosphate in seawater. The MoP-CTAB compound could be efficiently extracted on an in-line Sep-Pak C18 cartridge, and rapidly eluted by 0.3 mol l(-1) sulphuric acid-ethanol solution. Then the compound was reduced by luminol to produce chemiluminescence light, which could be detected using a luminescence analyzer. Experimental parameters were optimized using a univariate experimental design. Using artificial seawater with salinity of 35 as a matrix, the standard curve with a linear range between 0.005 and 0.194 micromol l(-1) had been obtained, and the recovery and the detection limit of the proposed method were found to be 92.5% and 0.002 micromol l(-1), respectively. The relative standard deviation (R.S.D.), which was determined over eight hour, was 4.66% (n=7) for the artificial seawater at a concentration of 0.097 micromol l(-1) orthophosphate. Si of 200 micromol l(-1) would not interfere with the detection of 0.012 micromol l( 1) orthophosphate compound. Three typical seawater samples were analyzed using both the proposed method and the magnesium hydroxide-induced coprecipitation (MAGIC) method, and the results of the two methods showed no significant difference using the t test. Compared to the MAGIC method, the proposed method was more sensitive, time saving and easy for on-line analysis. PMID- 17723438 TI - Gas chromatographic-mass spectrometric analysis of N-acetylated amino acids: the first case of aminoacylase I deficiency. AB - During the metabolic work-up of a patient presenting with neonatal convulsions, we consistently observed the presence of unusual peaks in the gas chromatographic mass spectrometric analysis of urinary organic acids. The gas chromatographic mass spectrometric characteristics of the unusual peaks suggested that they corresponded to derivatives of N-acetylated amino acids. The tentative identification was confirmed by the identity of retention times and mass spectra of the trimethylsilyl derivatives of the authentic compounds. We describe our observations that led to the identification of the various N-acetylated amino acids in this first patient with a confirmed deficiency of aminoacylase I, an enzyme involved in the cytosolic degradation of N-terminally modified proteins. The potential and limitations of urinary organic acid analysis for the detection of N-acetylated amino acids was further studied using pure compounds. In addition, we provide mass spectral data for 37 trimethylsilyl derivatives from 17 N-acetylated amino acids, most of which have not been reported previously. Our data provide valuable information that will help the clinical laboratorians who are responsible for organic acid analysis to recognize this new condition and could aid its detection in other patients. PMID- 17723439 TI - A new immune resonance scattering spectral assay for trace fibrinogen with gold nanoparticle label. AB - Gold nanoparticles in size of 9.0 nm was prepared by the trisodium citrate and used to label goat anti-human fibrinogen. In the pH 6.2 buffer solution and in the presence of polyethylene glycol (PEG), the immune reaction between gold labeled goat anti-human fibrinogen and fibrinogen took place and the labeled gold nanoparticles were released from the goat anti-human fibrinogen, and the released gold particles aggregated which leaded the resonance scattering intensity at 560 nm (I560 nm) to enhance greatly. The I560 nm is proportional to the fibrinogen concentration in the range from 0.027 to 1.07 microg mL(-1). The detection limit is 1.14 ng mL(-1). This simple assay was applied to determination of fibrinogen in human plasma, with satisfactory results. PMID- 17723440 TI - Size effect in thiol and amine binding to small Pt nanoparticles. AB - A study was carried out to compare the binding affinities of 1-dodecanethiol and dodecylamine for small Pt nanoparticles. The results showed that the affinity of thiol for Pt nanoparticles increases with increasing particle size whereas the affinity of amine for Pt nanoparticles decreases. The divergence in binding affinities has resulted in differences in catalytic activities of thiol- and amine-protected Pt nanoparticles in the room temperature electro-oxidation of methanol (a fuel cell reaction). It was therefore possible for the larger Pt nanoparticles to be catalytically more active than the smaller Pt nanoparticles up to a certain critical size, before the surface area effects of nanoparticles become noticeable. PMID- 17723441 TI - Attachment of nickel hexacyanoferrates nanoparticles on carbon nanotubes: preparation, characterization and bioapplication. AB - The successful attachment of nickel hexacyanoferrate nanoparticles to carbon nanotubes through a simple, two-step procedure is reported. Histidine can be covalently linked to the carbon nanotube surface, which can then be used as interlinker for the binding of nickel hexacyanoferrate nanoparticles. A detailed investigation by Fourier transform infrared spectra (FT-IR), transmission electron microscopy, UV-vis and electrochemistry was performed in order to elucidate the preparation process and properties of the nanocomposites. Abundant nanoparticles were found attached onto the carbon nanotube surface and the nanocomposites are highly stable. Additionally, the nanostructure exhibits more efficient electron transfer ability and larger electrochemical response towards hydrogen peroxide as compared to the nanoparticles and carbon nanotubes physically mixed together. With the immobilization of cholesterol oxidase onto the nanostructure modified electrode surface, a biosensor that responds sensitively to cholesterol has been constructed. In pH 6.98 phosphate buffer, an almost interference free determination of cholesterol has been observed at -0.2V versus SCE with a linear range from 0.005 to 3mM and response time <20s. PMID- 17723442 TI - Electronic micropipettor: a versatile fluid propulsion and injection device for micro-flow analysis. AB - The shortage of ready to use small sized liquid propulsion and switching devices for microfluidic cells (micro-cell) is a bottleneck in the dissemination of micro flow analysis (mu-FA), now that microfluidic electrochemical cells can be designed and assembled in any laboratory by thermal transfer of laser printed masks and CD-Rs. Microprocessor-controlled electronic pipettors, commercially available with minimum capacity of 10 microL, represent a compromise solution between oversized peristaltic pumps and tiny "on a chip" micropumps and valves. The versatility of the electronic pipette coupled with the mu-cell (13-microm deep longitudinal channel) was demonstrated in three operation modes: SIA like, FIA like and direct injection analysis (DIA). Injections of 100 nL K4Fe(CN)6 (0.1 mol L(-1) KCl) define a linear analytical curve (r=0.999) in the range of 5 x 10( 7) to 1.0 x 10(-3) mol L(-1) for flow amperometry at a gold electrode potentiostated at 0.4V versus Ag/AgCl. Methods for the amperometric mu-flow determination of promethazine (FIA like), dipyrone (SIA like) and chlorpromazine (DIA) in pharmaceutical formulations were developed and applied to real samples. Excellent linearity of analytical curves and high repeatability (R.S.D.<3.0%) at the low picomole range was obtained and all results for real samples were in agreement with reference methods. The results reflect the stability and the reliability of the setups envisioned for the electronic pipette coupled with amperometric mu-cell and the validity of the mu-FA methods. PMID- 17723443 TI - On-chip integrated hydrolysis, fluorescent labeling, and electrophoretic separation utilized for acetylcholinesterase assay. AB - A sensitive on-chip acetylcholinesterase (AChE) assay that serves as a basis for the development of a fully integrated on-chip AChE-inhibitor detection assay is presented. The sequential steps required for the on-chip analysis process were integrated into a microchip. Transport and mixing of the reagents occurred by a combination of electroosmosis and electrophoresis using computer-controlled electrokinetic transport. AChE-catalyzed hydrolysis of acetylthiocholine to thiocholine was determined by on-chip reaction of thiocholine with eosinmaleimide, and the resulting thioether was electrophoretically separated and detected by laser-induced fluorescence (LIF). Enzyme-substrate mixing and reaction by confluent flow of reagents was compared with electrophoretically mediated microanalysis (EMMA), based on injection of an enzyme plug, and the utilization of differences in electrophoretic mobility as a driving force for efficient mixing and reaction. Both methods yielded similar results, however the EMMA-plug technique is preferable. The EMMA-plug technique was optimized for length and pushing time of enzyme plug, length of dyes mixture plug, acetylthiocholine concentration, and detector location. Detection of O-ethyl S-[2 (diisopropylamino)ethyl] methylphosphonothiolate (VX) and paraoxon, two AChE inhibitors, was demonstrated by off-chip mixing of the inhibitor and AChE, followed by the on-chip AChE assay. Limit of detection of VX for 5.5 min incubation and of paraoxon for 8 min incubation was 4x10(-10) and 4x10(-7) M, respectively. Utilization of the AChE microchip assay for inhibition kinetics was demonstrated also by evaluation of the inhibitor-enzyme bimolecular reaction constant (k(i)). The evaluated k(i) values for VX and paraoxon for AChE from the electric eel were 3.5 x 10(7) and 1.7 x 10(5) M(-1) min(-1), respectively, conforming well to reported values obtained by bulk methods. PMID- 17723444 TI - Monolithic molecularly imprinted polymer for sulfamethoxazole and molecular recognition properties in aqueous mobile phase. AB - A monolithic molecularly imprinted polymer (monolithic MIP) for sulfamethoxazole (SMO) was prepared by in situ polymerization method as the HPLC stationary phase. By optimizing the polymerization conditions, the monolithic MIP showed highly specific recognition for the template SMO over its three structurally related analogs. As shown by SEM and the pore size distribution profile, the resultant MIP monolith showed a main pore diameter of 594 nm and a large specific surface area of 124 m2 g(-1), this allowed the mobile phase to flow through the column with low backpressure. Furthermore, the recognition abilities of the monolithic MIP in aqueous and organic media were studied. The results exhibited that the monolithic MIP possessed excellent recognition ability in aqueous media. Hydrophobic interactions, in addition to shape recognition, were the dominant effect for recognition in the mobile phase with high water content. Moreover, the binding sites and the dissociation constant were also determined by frontal chromatography as 122 micromol g(-1) and 1.88 x 10(-5)mol L(-1), respectively, which demonstrated that the obtained SMO-MIP monolith had a high binding capacity and strong affinity ability to the template molecule. Furthermore, the resultant SMO-MIP monolith was used as HPLC column directly to determine the SMO contents in three kinds of pharmaceutical tablets with the optimized aqueous mobile phase. PMID- 17723445 TI - A surface-fluorinated-TiO2-KMnO4 photocatalytic system for determination of chemical oxygen demand. AB - A new method for chemical oxygen demand (COD) determination has been developed, based on photocatalytic oxidative degradation by using a fluorinated-TiO2-KMnO4 system. In such a system, a linear correlation is observed between the amount of oxidizable dissolved organic matter and the amount of MnO4- consumed by the coupled reduction process. Thus, the COD determination is transformed to a simple and direct determination of the deletion of MnO4-. The surface fluorination of TiO2 nanoparticles can enhance the rate of photocatalytic oxidation of organic matter and the rate of coupled photocatalytic reduction of MnO4-. This makes the method be rapid, environment friendly and easy for operation. Under optimized conditions, this method can respond linearly to COD of potassium hydrogen phthalate (KHP) in the range of 0.1-280 mg L(-1), with a detection limit of 0.02 mg L(-1) COD. The COD in samples of tap water, lake water and paper industry sewage has been determined satisfactorily by using this method. PMID- 17723446 TI - Multi-way modeling of hydro-chemical data of an alluvial river system--a case study. AB - A large data set pertaining to water quality of an alluvial river was analyzed using multi-way data analysis methods with a view to extract the hidden information, spatial and temporal variation trends in the river water quality. Four-way data (8 monitoring sites x 22 water quality variables x 10 monitoring years x 12 sampling months) analysis was performed using PARAFAC and Tucker3 models. A two component PARAFAC model, although explained 35.1% of the data variance, could not fit to the data set. Tucker3 model of optimum complexity (2,3,1,3) explaining 39.7% of the data variance, allowed interpretation of the data information in four modes. The model explained spatial and temporal variation trends in terms of water quality variables during the study period and revealed that sampling sites in mid-stretch of the river were dominated mainly by the variables of anthropogenic origin. The results delineated the mid stretch of the river as critical from pollution point of view and also identified summer months as having high influence on river water quality in this stretch. The information regarding spatial and temporal variations in water quality generated by the four-way modeling of data would be useful in developing long-term water resources management strategies in the river basin. PMID- 17723447 TI - Chemical speciation of Co, Ni, Cu, and Zn in mine effluents and effects of dilution of the effluent on release of the above metals from their metal dissolved organic carbon (DOC) complexes. AB - The paper explores the lability of DOC complexes of Co, Ni, Cu, and Zn in the mining effluent, and investigates the effects of dilution of the effluent on the release of metals from the metal-DOC complexes. This study was done using competing ligand exchange method in conjunction with adsorptive cathodic stripping voltammetry on effluent samples from Copper Cliff Mine, Sudbury, Canada, using two samples of the effluent: one, undiluted (100%) effluent, and the other, diluted (45%) effluent. The dilution was done with tap water in order to determine the effects of dilution on the metal complexes in the effluents when they were discharged into receiving streams of freshwaters. The dilution of the effluent had a small effect on release of Cu from the Cu-DOC complexes, but had a much greater effect on the release of Zn from the Zn-DOC complexes. The release of Ni and Co from their DOC complexes decreased drastically on dilution of the effluent. The much greater release of Cu from the Cu-DOC complexes compared to the release of Ni, Co, and Zn from their DOC complexes in both the undiluted and the diluted effluent was probably due to the higher absolute concentration of Cu and the higher [Cu]/[DOC] ratio. The drastic decrease in the release of Ni and Co from the Ni- and Co-DOC complexes in the diluted (45%) effluent compared with the undiluted (100%) effluent probably resulted from strengthening of the metal-DOC bond due to the reduced screening of charges by a smaller concentration of Ca2+ in the diluted (45%) effluent. This work also shows that change in the ionic strength produces conformational changes in and in aggregation and precipitation of the DOC and also changes in electrostatic interactions between the metal cations and the humate polyanions. PMID- 17723448 TI - Analysis of heavy metals in road-deposited sediments. AB - Road-deposited sediments were analysed for heavy metal concentrations at three different landuses (residential, industrial, commercial) in Queensland State, Australia. The sediments were collected using a domestic vacuum cleaner which was proven to be highly efficient in collecting sub-micron particles. Five particle sizes were analysed separately for eight heavy metal elements (Zn, Fe, Pb, Cd, Cu, Cr, Al and Mn). At all sites, the maximum concentration of the heavy metals occurred in the 0.45-75 microm particle size range, which conventional street cleaning services do not remove efficiently. Multicriteria decision making methods (MCDM), PROMETHEE and GAIA, were employed in the data analysis. PROMETHEE, a non-parametric ranking analysis procedure, was used to rank the metal contents of the sediments sampled at each site. The most polluted site and particle size range were the industrial site and the 0.45-75 microm range, respectively. Although the industrial site displayed the highest metal concentrations, the highest heavy metal loading coincided with the highest sediment load, which occurred at the commercial site. GAIA, a special form of principal component analysis, was applied to determine correlations between the heavy metals and particle size ranges and also to assess possible correlation with total organic carbon (TOC). The GAIA-planes revealed that irrespective of the site, most of the heavy metals are adsorbed to sediments below 150 microm. A weak correlation was found between Zn, Mn and TOC at the commercial site. This could lead to higher bioavailability of these metals through complexation reactions with the organic species in the sediments. PMID- 17723450 TI - Optimization of transmission near infrared spectrometry procedures for quality control of pesticide formulations. AB - The use of different response functions to be optimized in the frame of the use of near infrared spectrometry for quality control of active principles in agrochemical formulations has been evaluated. Both, simple functions, based on parameters like sensitivity, repeatability, accuracy, signal to noise ratio, limit of detection or sample throughput, and a complex function, considering all the aforementioned aspects, were employed in the development of a new method for Iprodione determination in agrochemicals. Optimization strategies were based on the previous screening of the most important instrumental factors like number of cumulated scans, nominal resolution, mirror velocity and zero filling factor, based on a two-level full factorial design and on the search for the optimum conditions using central composite designs. Data found evidenced the influence of the response function on the optimum values of experimental conditions and could be employed as a general guide to evaluate the experimental factors in routine use of near infrared spectrometry. Finally the optimized method for Iprodione has been applied to the determination of Diuron and results found compared with those obtained by a conventional approach. PMID- 17723449 TI - Isotope dilution-thermal ionisation mass spectrometric analysis for tin in a fly ash material. AB - Isotope dilution-thermal ionisation mass spectrometry (ID-TIMS) analysis has been applied to the determination of tin in a fly ash sample supplied by the EC Joint Research Centre (Ispra, Italy). The proposed procedure includes the silica gel/phosphoric acid technique for tin thermal ionisation activation and a strict heating protocol for isotope ratio measurements. Instrumental mass discrimination factor has been previously determined measuring a natural tin standard solution. Spike solution has been prepared from 112Sn-enriched metal and quantified by reverse isotope dilution analysis. Two sample aliquots were spiked and tin was extracted with 4.5M HCl during 25 min ultrasound exposure time. Due to the complex matrix of this fly ash material, a two-step purification stage using ion exchange chromatography was required prior TIMS analysis. Obtained results for the two sample-spike blends (10.11+/-0.55 and 10.50+/-0.64 micromol g(-1)) are comparable, both value and uncertainty. Also a good reproducibility is observed between measurements. The proposed ID-TIMS procedure, as a primary method and due to the lack of fly ash reference materials certified for tin content, can be used to validate more routine methodologies applied to tin determination in this kind of samples. PMID- 17723451 TI - Validation and uncertainty assessment of rapid extraction and clean-up methods for the determination of 16 organochlorine pesticide residues in vegetables. AB - Rapid and practical extraction methods were developed using dichloromethane and ethyl acetate for the routine determination of 16 organochlorine pesticide residues and applied to approximately 30 fresh vegetables (tomato, cucumber and pepper) by using GC-ECD. The procedures were validated. Measurement uncertainties were calculated by applying bottom-up approach. The average recoveries obtained for each pesticide ranged between 65 and 102% at three fortification levels. The uncertainties of the analytical methods were lower than 21 and 16% with and without recovery correction, respectively. The calculated limits of detection and quantification were typically less than 1 ng g(-1) that were much lower than the maximum residue levels. PMID- 17723452 TI - Evaluation of calix-crown ionophores for selective separation of radio-cesium from acidic nuclear waste solution. AB - Extraction of Cs-137 from nitric acid was carried out using nitrobenzene solutions of calix-crowns such as calix[4]arene-bis(crown-6) (CC-A), calix[4]arene-bis(benzo crown-6) (CC-B) and calix[4]arene-bis(napthocrown-6) (CC C). CC-C was found to be superior extractant for Cs(I) as compared to the other two calix-crown ligands used in the present study. The effect of diluent on the extraction of Cs(I) indicated the trend: nitrobenzene>dichloroethane>chloroform>decanol>>carbon tetrachloride approximately n-hexane approximately toluene. Subsequently, the studies were carried out with nitrobenzene solutions of the calix-crown ligands (mainly CC-C) on the effects of (a) aqueous phase acidity, (b) ligand concentration, and (c) cesium concentration on Cs extraction from nitric acid media. Conditions for quantitative extraction and stripping were optimized and the extracted species conformed to {[CsL]+.[NO3]-.nH2O}. Selectivity studies were carried out using an irradiated natural U target involving tracer amount of fission products activities. Extraction of Cs(I) from a synthetic high level waste solution was also carried out. The promising results obtained in the present studies indicate possible use of the calix-crown ligand for Cs(I) recovery from the acidic high level waste. PMID- 17723453 TI - Handling complex effects in slurry-sampling-electrothermal atomic absorption spectrometry by multivariate calibration. AB - Analysis of solid samples by slurry-sampling-electrothermal atomic absorption spectrometry (SS-ETAAS) can imply spectral and chemical interferences caused by the large amount of concomitants introduced into the graphite furnace. Sometimes they cannot be solved using stabilized temperature platform furnace (STPF) conditions or typical approaches (previous sample ashing, use of chemical modifiers, etc.), which are time consuming and quite expensive. A new approach to handle interferences using multivariate calibrations (partial least squares, PLS, and artificial neural networks, ANN) is presented and exemplified with a real problem consisting on determining Sb in several solid matrices (soils, sediments and coal fly ash) as slurries by ETAAS. Experimental designs were implemented at different levels of Sb to develop the calibration matrix and assess which concomitants (seven ions were considered) modified the atomic signal mostly. They were Na+ and Ca2+ and they induced simultaneous displacement, depletion (enhancement) and broadening of the atomic peak. Here it is shown that these complex effects can be handled in a reliable, fast and cost-effective way to predict the concentration of Sb in slurry samples of several solid matrices. The method was validated predicting the concentrations of five certified reference materials (CRMs) and studying its robustness to current ETAAS problems. It is also shown that linear PLS can handle eventual non-linearities and that its results are comparable to more complex (non-linear) models, as those from ANNs. PMID- 17723455 TI - A disposable immunosensor for detection of 17beta-estradiol in non-extracted bovine serum. AB - This paper reports the assembly of a disposable immunosensor based on the direct competitive enzyme-linked immunosorbent assay (ELISA), for simple and fast measurement of 17beta-estradiol (17beta-E2) in bovine serum, using screen-printed electrodes (SPEs) and a Palm-Sens portable electrochemical detector. The immunosensor strip was assembled immobilising, by passive adsorption, anti-rabbit IgG onto the surface of the working SPE electrode. After the interaction between anti-rabbit IgG and rabbit anti-17beta-E2 polyclonal antibodies (PAb), the competition was performed using 17beta-estradiol-alkaline phosphatase conjugate (17beta-E2-AP) synthesised in our laboratory. The enzymatic substrate used for signal generation was 1-naphthylphosphate and its conversion to an electroactive product (1-naphthol) was measured using differential pulse voltammetry (DPV). To develop a prototype for field measurements, the entire competitive protocol has been optimised directly in a blank non-extracted bovine serum. According to the new EU criteria established by the Commission Decision 2002/657/EC for qualitative and quantitative screening methods, the detection capability (CCbeta), was determined. The CCbeta value resulted below the action limit (40 pg mL(-1)) fixed for 17beta-E2) Spiked and real samples were analysed using the electrochemical immunostrips obtaining precision values (relative standard deviation, R.S.D.%) ranging from 8.6 to 17.0% and a recovery (R%) from 88.2 to 120.0%. Results obtained on real samples were confirmed by liquid chromatography coupled on-line with tandem mass spectrometry (LC-MS/MS) using an atmospheric pressure chemical ionisation (APCI) source and a heated nebulizer (HN) interface; this is the method currently used to confirm illegal hormone administration for regulatory purposes. The disposable immunosensor appears suitable as a screening tool for field analysis of bovine serum estradiol. PMID- 17723454 TI - Novel potentiometric and optical silver ion-selective sensors with subnanomolar detection limits. AB - Ten Ag+-selective ionophores have been characterized in terms of their potentiometric selectivities and complex formation constants in solvent polymeric membranes. The compounds with pi-coordination show much weaker interactions than those with thioether or thiocarbamate groups as the coordinating sites. Long-term studies with the best ionophores show that the lower detection limit of the best Ag+ sensors can be maintained in the subnanomolar range for at least 1 month. The best ionophores have also been characterized in fluorescent microspheres. The so far best lower detection limits of 3 x 10(-11) M (potentiometrically) and 2 x 10( 11) M Ag+ (optically) are found with bridged thiacalixarenes. PMID- 17723456 TI - Electrochemical deposition of sol-gel films for enhanced chromium(VI) determination in aqueous solutions. AB - A pyridine-functionalized sol-gel film has been formed by electrodeposition at a glassy carbon electrode surface. When this protonated film is exposed to a Cr(VI) solution, the Cr(VI) anions are preconcentrated at the electrode surface. Using square wave voltammetry, the Cr(VI) species are reduced to Cr(III), and a peak current corresponding to this reduction is generated at 0.17V. The peak currents can be correlated with the Cr(VI) concentration. The functionalized sol-gel films demonstrated an enhanced sensitivity for Cr(VI) in aqueous solutions, providing a limit of detection at the low ppb level. Interference studies also displayed the high selectivity of the films for Cr(VI), and the system was able to tolerate a large excess of Cr(III) with no adverse affects. The reported electrodeposition method of film formation uses commercially available reagents and yields films quickly and reproducibly. The growth of these sol-gel films was monitored using an electrochemical quartz crystal microbalance (EQCM), and they were characterized by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). The reported work shows the promise of such an electrode for use in Cr(VI) sensing applications. PMID- 17723457 TI - Preventing inhibition of tyrosinase with modified electrodes. AB - Wines, especially red wines, contain numerous biologically active compounds, the most important of which are polyphenols, whose nutritional importance is attributed to their antioxidant power. Because of this, the detection of the amount of phenolic compounds in red wines becomes extremely important. However, using free enzyme in the determination of phenolic compounds in wines cannot reflect the actual values since there are also naturally found inhibitors in red wines. In this study, benzoic acid, cinnamic acid, and sorbic acid were utilized to understand the behavior of immobilized polyphenol oxidase in the conducting polymer matrices toward inhibition. Cinnamic acid was found to be the most powerful inhibitor for both free and immobilized enzyme in copolymer matrix of poly(terephthalic acid bis-(2-thiophen-3-yl-ethyl) ester) (PTATE) with polypyrrole (PPy). In the case of immobilized enzyme in PPy matrix, it was observed that sorbic acid is a stronger inhibitor than cinnamic acid. The inhibitory effects of these inhibitors on PPO were compared with respect to both the structural differences of inhibitors and conducting polymer matrices. PMID- 17723458 TI - Speciation analysis of selenium in natural water using square-wave voltammetry after preconcentration on activated carbon. AB - A simple, accurate, sensitive and selective method was described for rapid determination of ultra-trace quantities of selenium. Selenium(IV) was collected on activated carbon (AC) after reduction to elemental Se by l-ascorbic acid. The collected selenium was then dissolved by oxidation reaction with bromate in acidic media and was indirectly determined through the bromide formation using square-wave voltammetry (OSWV). The total amount of Se(IV) and Se(VI) was collected on AC after its reduction by hydrazine. Selenium in the range 0.01-20 microg L(-1) could be determined by this method. The method was used to the determination of Se(IV) and Se(VI) in natural water with satisfactory results. PMID- 17723459 TI - Ultrasonic acoustic wave detection of single or capillary electrophoretically resolved underivatized amino acids. AB - Acoustic wave detection of various underivatized amino acids that were hydrodynamically introduced into and electrokinetically migrated along a capillary tube has been achieved. The detection principle is based on the measurement of the ultrasonic absorption and density change of the aqueous amino acid samples as they pass by the detection zone. Acoustic wave detection of underivatized leucine was obtained in the ultrasonic frequency range of 100 kHz to 20 MHz. This was accomplished by measuring the insertion loss from the vector ratio of the signal voltage to the source voltage obtained at the generating and receiving piezoelectric transducers. Linear concentration dependence of the insertion loss of underivatized leucine was established. The effects of capillary internal diameter, capillary geometry (square and circular), buffer concentration, buffer pH and acoustic wave frequency on the insertion loss were investigated. Subsequently, separations of underivatized amino acids (leucine/histidine and leucine/tryptophan) were performed under different buffer conditions and different capillary geometry. PMID- 17723460 TI - Analysis of fatty acids in lung tissues using gas chromatography-mass spectrometry preceded by derivatization-solid-phase microextraction with a novel fiber. AB - In this article, a laboratory-made sol-gel derived fiber with butyl methacrylate/hydroxy-terminated silicone oil (BMA/OH-TSO) coating was first used for headspace solid-phase microextraction (HS-SPME) of medium and long chain fatty acids after derivatization and applied to the analysis of fatty acids in lung tissues by coupling to gas chromatography-mass spectrometry (GC-MS). The experimental parameters for derivatization, HS-SPME and desorption were optimized. Fatty acids in cancerous lung tissues from five patients with lung cancer were determined under the optimized conditions. Normal lung tissues from the same five patients were used as controls. This fiber showed higher extraction efficiency for fatty acids after derivatization when compared with commercial polydimethylsiloxane (PDMS) and polydimethylsiloxane-divinylbenzene (PDMS/DVB) fibers due to the three-dimensional network in the coating. The method presented in this paper showed satisfactory precision, accuracy, linearity and limits of detection (LODs). The relative standard deviation values were below 13.3% (n=5) and the recoveries obtained ranged from 76.35% to 107.0%. The results obtained using the SPME method were also compared with those got by using liquid-liquid extraction (LLE) technique. It was found that the sensitivity could be enhanced by the SPME method. The analysis of the cancerous lung tissues and normal controls from five patients with lung cancer indicated that the main components of lung tissue were palmitic acid (C16:0), stearic acid (C18:0) and lignoceric acid (C24:0). A comparison between the levels of the fatty acids in cancerous lung tissues and normal controls from the same a patient with lung cancer shows that most of the saturated fatty acids showed higher levels in cancerous lung tissues, while unsaturated fatty acids showed higher levels in normal controls on the whole. PMID- 17723461 TI - On-line preconcentration and separation of Co, Ni and Cd via capillary microextraction on ordered mesoporous alumina coating and determination by inductively plasma mass spectrometry (ICP-MS). AB - In this paper, an ordered mesoporous alumina coating was prepared and applied to capillary microextraction (CME) of trace Co, Ni and Cd for the first time. The coated capillary was used for on-line coupling CME with inductively plasma mass spectrometry (ICP-MS) for the determination of trace metals of Co, Ni and Cd. The porous structure of Al2O3 coating was examined by SEM and TEM. The effects of the extraction parameters including pH, sample flow rate and volume, elution solution and interfering ions on the recovery of analytes have been investigated and optimized. Under the optimized conditions, the limits of detection were 0.33, 1.5 and 1.4 ng L(-1) for Co, Ni and Cd, respectively, with a preconcentration factor of 10 times. The precisions for all investigated elements were 2.7, 4.1 and 2.5% (c=0.05 ng L(-1), n=7), for Co, Ni and Cd, respectively, and the sample frequency was 8 h(-1). The proposed method was successfully applied for the analysis of trace metals in water, rice and urine samples with the recovery of 94-105%. In order to validate the proposed method, two certified reference materials of GBW 0913 human urine and NIES No.10-b rice flour were analyzed, and the determination values are in good agreement with the certified values. The ordered mesoporous Al2O3 coated capillary can be used more than 20 times without decreasing the extraction efficiency. PMID- 17723462 TI - A study of the analytical behaviour of selected synthetic and naturally occurring quinolines using electrospray ionisation ion trap mass spectrometry, liquid chromatography and gas chromatography and the construction of an appropriate database for quinoline characterisation. AB - Mass spectral fragmentation of quinoline alkaloids of significance in plants has been investigated using electrospray ionisation ion trap mass spectrometry (ESI MS(n)) with a view to characterisation of molecules of unknown structure isolated from these natural sources. This investigation has led to the generation of an appropriate database incorporating data from ESI-MS(n) and also from gas liquid chromatography (GLC) and liquid chromatography (HPLC) for these low molecular mass quinolines. This has been put to practical application in the identification of quinoline alkaloids in a plant extract. Thus, an acid extraction of the leaves of Choisya ternata containing such tertiary alkaloids was analysed by liquid chromatography-electrospray ionisation mass spectrometry (HPLC-ESI-MS) and the resulting behaviour of the quinolines was compared with that of the quinoline alkaloids in the database. PMID- 17723463 TI - Feasibility study on qualitative and quantitative analysis in tea by near infrared spectroscopy with multivariate calibration. AB - This study attempted the feasibility to use near infrared (NIR) spectroscopy as a rapid analysis method to qualitative and quantitative assessment of the tea quality. NIR spectroscopy with soft independent modeling of class analogy (SIMCA) method was proposed to identify rapidly tea varieties in this paper. In the experiment, four tea varieties from Longjing, Biluochun, Qihong and Tieguanyin were studied. The better results were achieved following as: the identification rate equals to 90% only for Longjing in training set; 80% only for Biluochun in test set; while, the remaining equal to 100%. A partial least squares (PLS) algorithm is used to predict the content of caffeine and total polyphenols in tea. The models are calibrated by cross-validation and the best number of PLS factors was achieved according to the lowest root mean square error of cross validation (RMSECV). The correlation coefficients and the root mean square error of prediction (RMSEP) in the test set were used as the evaluation parameters for the models as follows: R=0.9688, RMSEP=0.0836% for the caffeine; R=0.9299, RMSEP=1.1138% for total polyphenols. The overall results demonstrate that NIR spectroscopy with multivariate calibration could be successfully applied as a rapid method not only to identify the tea varieties but also to determine simultaneously some chemical compositions contents in tea. PMID- 17723464 TI - The potential of Raman spectroscopy for characterisation of the fatty acid unsaturation of salmon. AB - Raman spectroscopy has been evaluated for characterisation of the degree of fatty acid unsaturation (iodine value) of salmon (Salmo salar). The Norwegian Quality Cuts from 50 salmon samples were obtained, and the samples provided an iodine value range of 147.8-170.0 g I2/100 g fat, reflecting a normal variation of farmed salmon. Raman measurements were performed both on different spots of the intact salmon muscle, on ground salmon samples as well as on oil extracts, and partial least squares regression (PLSR) was utilised for calibration. The oil spectra provided better iodine value predictions than the other data sets, and a correlation coefficient of 0.87 with a root mean square error of cross-validation of 2.5 g I2/100 g fat was achieved using only one PLSR component. The ground samples provided comparable results, but at least two PLSR components were needed. Higher prediction errors were obtained from Raman spectra of intact salmon muscle, and this may partly be explained by sampling uncertainties in the relation between Raman measurements and reference analysis. All PLSR models obtained were based on chemically sound regression coefficients, and thus information regarding fatty acid unsaturation is readily available from Raman spectra even in systems with high contents of protein and water. The accuracy, the robustness and the low complexity of the PLSR models obtained suggest Raman spectroscopy as a promising method for rapid in-process control of the degree of unsaturation in salmon samples. PMID- 17723465 TI - Improving the robustness of a partial least squares (PLS) model based on pure component selectivity analysis and range optimization: case study for the analysis of an etching solution containing hydrogen peroxide. AB - Pure component selectivity analysis (PCSA) was successfully utilized to enhance the robustness of a partial least squares (PLS) model by examining the selectivity of a given component to other components. The samples used in this study were composed of NH4OH, H2O2 and H2O, a popular etchant solution in the electronic industry. Corresponding near-infrared (NIR) spectra (9000-7500 cm(-1)) were used to build PLS models. The selective determination of H2O2 without influences from NH4OH and H2O was a key issue since its molecular structure is similar to that of H2O and NH4OH also has a hydroxyl functional group. The best spectral ranges for the determination of NH4OH and H2O2 were found with the use of moving window PLS (MW-PLS) and corresponding selectivity was examined by pure component selectivity analysis. The PLS calibration for NH4OH was free from interferences from the other components due to the presence of its unique NH absorption bands. Since the spectral variation from H2O2 was broadly overlapping and much less distinct than that from NH(4)OH, the selectivity and prediction performance for the H2O2 calibration were sensitively varied depending on the spectral ranges and number of factors used. PCSA, based on the comparison between regression vectors from PLS and the net analyte signal (NAS), was an effective method to prevent over-fitting of the H2O2 calibration. A robust H2O2 calibration model with minimal interferences from other components was developed. PCSA should be included as a standard method in PLS calibrations where prediction error only is the usual measure of performance. PMID- 17723466 TI - Robustness study of a reversed-phase liquid chromatographic method for the analysis of carboxylic acids in industrial reaction mixtures. AB - The robustness study of the reversed-phase liquid chromatographic method developed for the quantitative analysis of carboxylic acids is a real asset to prepare method transfer because it provides an indication of its reliability during routine use. Indeed, it was possible to predict the consequences of small variations in operating conditions on the responses. The design of experiments approach was applied to model the effects and interactions of a high number of factors varying simultaneously with a limited number of runs. First we identified the factors which potentially affect the chromatographic responses used for carboxylic acids quantitation: detection wavelength (lambda), column temperature (T), acetonitrile ratio in mobile phase (Me), duration of the plateau before the gradient (L) and gradient slope (S). Then we estimated the order of magnitude of realistic variations to assign factor levels. Finally a central composite design was carried out around the nominal conditions defined during method optimization. The statistical treatment of responses (retention factors, and concentrations) showed that the column temperature, the acetonitrile ratio in the mobile phase, the duration of the plateau before the gradient and the gradient slope were the most influent factors. The building of the robust domain from response-surfaces allowed us to give tolerance limits for the factors (216 nm< lambda <222 nm, 49.3 degrees C < T < 51.4 degrees C, 4.90% < Me < 5.18%, v/v, 4.5 min < L < 5.4 min, 9%< S <11%) for which the performances of the method were maintained. PMID- 17723467 TI - Development and validation of an analytical method for the determination of semicarbazide in fresh egg and in egg powder based on the use of liquid chromatography tandem mass spectrometry. AB - In this work the development of a method to determine semicarbazide (SEM) in fresh whole egg and in whole egg and egg white powders as those used in the food industry, by using LC-MS/MS is described. The method is based on a recently validated one for the determination of SEM in baby food. SEM is extracted from egg with 0.2 mol L(-1) hydrochloric acid and derivatised with 2 nitrobenzaldehyde. The extract is neutralised and purified by passing through a solid phase extraction (SPE) cartridge. The 2-nitrobenzaldehyde derivative is eluted with ethyl acetate. The eluate is evaporated to dryness and the residue re dissolved in methanol:water mobile phase. SEM is determined by reversed-phase LC MS/MS. The "in-house" validation of this method has been performed taking into account the "Harmonized guidelines for single-laboratory validation of methods of analysis" (IUPAC Technical report) and the Commission Decision (2002/657/EC). The performance characteristics of the method were established by in-house validation procedures employing assays with standard solutions, sample blanks and spiked samples. Linearity, matrix effect, trueness, precision, selectivity, limits of detection and of quantification were determined. The fitness for purpose of this method was assessed based on its performance characteristics. LOD's of 0.15 and 0.4 microg kg(-1) for whole fresh egg and industrial egg powders, respectively, were obtained. The LOQ for fresh whole egg was 0.2 microg kg(-1) and for industrial egg powders 0.8 microg kg(-1). Linear calibration curves were obtained in the ranges 1-100 and 0.8-400 microg kg(-1) for fresh whole egg and the egg powders, respectively. PMID- 17723468 TI - Method validation approach on the basis of a quadratic regression model. AB - A method validation approach that bases on a quadratic regression model in which two types of error are incorporated is presented and applied to an experimental data set. The validation approach enables the determination of analytical performance characteristics referred to in Commission Decision 2002/657/EC (i.e., repeatability, within-laboratory reproducibility, decision limit, detection capability). PMID- 17723469 TI - Common components and specific weights analysis: a tool for monitoring the molecular structure of semi-hard cheese throughout ripening. AB - Twelve semi-hard (Raclette) cheeses, belonging to four brand products, namely A (n=3), B (n=3), C (n=3) and D (n=3), were produced during summer period and ripened at an industrial scale. Tryptophan, riboflavin and vitamin A fluorescence spectra were scanned on the 12 cheeses at 2, 30 and 60 days of ripening. The physico-chemical analyses were performed only at the end of the ripening stage (60 days). Common components and specific weights analysis (CCSWA) were applied on the four data tables. CCSWA showed that the common component 1 (q1), discriminating cheeses labelled A, B and C from those labelled D, expressed 94.4 and 59% of the inertia of vitamin A and tryptophan fluorescence spectra and a less amount for riboflavin fluorescence spectra and physico-chemical data (24.2 and 13.2%, respectively). Common component 3 (q3), differentiating between cheeses labelled B and those labelled A and C, explained 34.6 and 23.9% of the inertia of the physico-chemical data and tryptophan fluorescence spectra, respectively, and a tiny part of the inertia of riboflavin and vitamin A fluorescence spectra (3.2 and 0.7%, respectively). The CCSWA showed its ability to describe the overall information collected from fluorescence and physico chemical data tables and to extract relevant information at the molecular level throughout ripening of the investigated semi-hard cheeses. PMID- 17723470 TI - Synchronous-scan fluorescence as a selective detection method for sodium dodecylbenzene-sulfonate and pyrene in environmental samples. AB - Synchronous-scan fluorescence spectra of dodecylbenzene sulfonic acid sodium salt (SDBS) and pyrene in aqueous solution were studied. The concentration ranges of SDBS and pyrene in aqueous solutions were 0.01-10.00 and 0.001-0.050 mg L(-1), respectively. The optimized wavelength differences (Deltalambda) of 46-55 and 38 nm were maintained between excitation and emission wavelengths for SDBS and pyrene, respectively, and they were found to be suitable for effective determination of SDBS and pyrene without mutual interferences; the peaks were observed at lambda(ex) 229-232 nm (SDBS) and lambda(ex) 335 nm (pyrene). Linear relationships between synchronous-scan fluorescence spectroscopy (SFS) intensity and concentration of SDBS or pyrene in aqueous solution (Milli-Q water, river water, and mucus of fish gills) were established. It was demonstrated that SFS method was effective for simultaneous analyses of SDBS and pyrene in mixed solution. PMID- 17723471 TI - Enzymatic chemiluminescent assay of glucose by sequential-injection analysis with soluble enzyme and on-line sample dilution. AB - This work reports a sequential-injection analysis (SIA) method for the enzymatic assay of glucose with soluble glucose oxidase (GOD) and on-line sample dilution with chemiluminescence (CL) detection. A zone of sample was aspirated in the holding coil of the SIA manifold and, if necessary, was diluted on-line by means of an auxiliary dilution conduit. Then, a zone of GOD was aspirated adjacent to the sample zone and a stopped-flow period was applied to allow the enzymatic reaction to proceed with production of hydrogen peroxide. Then, zones of a catalyst (Co(II) solution) and alkaline luminol were aspirated into the holding coil. Finally, the flow was reversed and the stacked zones were sent to a flow cell located in front of a photomultiplier tube (PMT) that monitored the CL intensity. The linear dynamic range was 1 x 10(-5)-1 x 10(-3) mol L(-1) glucose, the coefficient of variation at 8 x 10(-5) mol L(-1) of glucose was s(r)=3.1% (n=8), the limit of detection at the 3sigma level was c(L)= 1 x 10(-6) mol L(-1) and the sampling frequency was 28 h(-1). With on-line dilution by a factor of 1/200, the linear range could be extended up to 0.2 mol L(-1) glucose. The advantages of the proposed method are the simple manifold and instrumentation used, the scope for automated on-line dilution, the low consumption of sample and reagents and the elimination of enzyme immobilisation procedures. The method was applied to the analysis of commercial drinks and honey with percent relative errors in glucose determination in the range 100+/-6.1%. PMID- 17723472 TI - Multi-pumping flow system for the determination of dissolved orthophosphate and dissolved organic phosphorus in wastewater samples. AB - A multi-pumping flow system (MPFS) for the spectrophotometric determination of dissolved orthophosphate and dissolved organic phosphorus in wastewater samples is proposed. The determination of orthophosphate is based on the vanadomolybdate method. In-line ultraviolet photo-oxidation is employed to mineralise organic phosphorus to orthophosphate prior to detection. A solenoid valve allows the deviation of the flow towards the UV-lamp to carry out the determination of organic phosphorus. Calibration was found to be linear up to 20 mg P L(-1), with a detection limit (3s(b)/S) of 0.08 mg P L(-1), an injection throughput of 75 injections h(-1) and a repeatability (R.S.D.) of 0.6% for the direct determination of orthophosphate. On the other hand, calibration graphs were linear up to 40 mg P L(-1), with a detection limit (3s(b)/S) of 0.5 mg P L(-1), an injection throughput of 11 injections h(-1) and a repeatability (R.S.D.) inferior to 2.3% for the procedures involving UV photo-oxidation. PMID- 17723473 TI - Flow-injection spectrophotometric determination of reverse transcriptase inhibitors used for acquired immuno deficiency syndrome (AIDS) treatment: focus on strategies for dealing with the background components. AB - This paper describes a rapid method for the quantification of reverse transcriptase inhibitors in mixtures of therapeutic interest containing zidovudine, zalcitabine and nevirapine. The method is based on a pH-gradient flow injection system with diode array detection and further data analysis using multivariate curve resolution. Data matrices of unknown samples mixtures have been analyzed simultaneously with those of standards and background via the construction of augmented data matrices. In this case, the spectral domain has been chosen for performing column-wise (i.e., wavelength-wise) matrix augmentation. The quantification is accomplished from the comparison of the analyte peaks resolved for unknown mixtures and standards, being peak areas the quantitative information to be correlated with the concentration in both calibration and prediction steps. The influence of background signal on the response is tackled through two main strategies involving modelling or subtraction. The potentiality of this method for the analysis of drugs in the presence of unknown interferences is demonstrated. Results obtained in the analysis of drug samples have proven the excellent performance of this method. Overall prediction errors in the quantification of two- and three-component mixtures are about 5-10%. PMID- 17723474 TI - Headspace liquid-phase microextraction using ionic liquid as extractant for the preconcentration of dichlorodiphenyltrichloroethane and its metabolites at trace levels in water samples. AB - A novel technique, high temperature headspace liquid-phase microextraction (HS LPME) with room temperature ionic liquid (RTIL), 1-butyl-3-methylimidazolium hexafluorophosphate ([C4MIM][PF6]) as extractant, was developed for the analysis of dichlorodiphenyltrichloroethane (p,p'-DDT and o,p'-DDT) and its metabolites including 4,4'-dichlorodiphenyldichloroethylene (p,p'-DDE) and 4,4' dichlorodiphenyldichloroethane (p,p'-DDD) in water samples by high performance liquid chromatography with ultraviolet detection. The parameters such as salt content, sample pH and temperature, stirring rate, extraction time, microdrop volume, and sample volume, were found to have significant influence on the HS LPME. The conditions optimized for extraction of target compounds were as follows: 35% NaCl (w/v), neutral pH condition, 70 degrees C, 800 rpm, 30 min, 10 microL [C4MIM][PF6], and 25 mL sample solutions. Under the optimized conditions, the linear range, detection limit (S/N=3), and precision (R.S.D., n=6) were 0.3 30 microg L(-1), 0.07 microg L(-1), and 8.0% for p,p'-DDD, 0.3-30 microg L(-1), 0.08 microg L(-1), and 7.1% for p,p'-DDT, 0.3-30 microg L(-1), 0.08 microg L(-1), and 7.2% for o,p'-DDT, and 0.2-30 microg L(-1), 0.05 microg L(-1), and 6.8% for p,p'-DDE, respectively. Water samples including tap water, well water, snow water, reservoir water, and wastewater were analyzed by the proposed procedure and the recoveries at 5 microg L(-1) spiked level were in the range of 86.8 102.6%. PMID- 17723475 TI - Pressurized liquid extraction as a novel sample pre-treatment for trace element leaching from biological material. AB - Pressurized liquid extraction (PLE), commonly used for organic compounds extraction, has been applied for trace element leaching from marine biological material in order to determine major and trace elements (Al, As, Cd, Co, Cu, Fe, Hg, Li, Mn, Pb, Se, Sr, V and Zn). The released elements by formic acid PLE have been evaluated by inductively coupled plasma-optical emission spectrometry (ICP OES). Different variables, such as formic acid concentration, extraction temperature, static time, extraction steps, pressure, mean particle size and diatomaceous earth (DE) mass/sample mass ratio were simultaneously studied by applying an experimental design approach (Plackett-Burman design (PBD) and central composite design (CCD)). Results showed that the extraction temperature was statistically significant (confidence interval of 95%) for most of the elements (high metal releasing was achieved at high temperatures). In addition, formic acid concentration was also statistically significant (confidence interval of 95%) for metals such as Cd and Cu. Most of the metals can be extracted using the same PLE operating conditions (formic acid concentration of 1.0 M, extraction temperature at 125 degrees C, static time of 5 min, one extraction step, extraction pressure at 500 psi and DE mass/sample mass ratio of 2). Taking in mind PLE requirements at the optimised operating conditions (125 degrees C), a time of 6 min is needed to pre-heat the cell. Therefore, the PLE assisted multi element leaching is completed after 12 min. Analytical performances, such as limits of detection and quantification, repeatability of the over-all procedure and accuracy, by analysing GBW-08571, DORM-2, DOLT-3 and TORT-2 certified reference materials, were finally assessed. PMID- 17723476 TI - Improved methods for urinary atrazine mercapturate analysis--assessment of an enzyme-linked immunosorbent assay (ELISA) and a novel liquid chromatography-mass spectrometry (LC-MS) method utilizing online solid phase extraction (SPE). AB - Elimination of interfering substances in urine by solid phase extraction (SPE) prior to analysis resulted in 10-fold improvement in the sensitivity of atrazine mercapturate (AM) enzyme-linked immunosorbent assay (ELISA) compared to previous reports. Of the two tested SPE systems, Oasis HLB and MCX, the mixed-mode MCX gave good recoveries (82%) of AM in spiked samples measured by ELISA, whereas the reverse-phase HLB phase was not compatible with the immunochemical method. At relatively high concentrations of urinary AM (>20 ng mL(-1)), sample dilution was effective enough for the elimination of interfering substances. The new liquid chromatography-mass spectrometry (LC-MS) method developed for AM utilizes online SPE with Oasis HLB, column switching and a stable-isotope internal standard. The limit of quantification (0.05 ng mL(-1)) indicates improved sensitivity compared with most previously published LC-MS methods for AM. Validation of all three methods, LC-MS, ELISA+SPE and ELISA+dilution with spiked urine samples showed good correlation between the known and measured concentrations with R2 values of 0.996, 0.957 and 0.961, respectively. When a set (n=70 plus 12 blind duplicates) of urine samples from farmers exposed to atrazine was analyzed, there was a good agreement (R2=0.917) between the log normalized data obtained by ELISA+SPE and LC MS. High correlation among the data obtained by the two tested methods and the LC MS method by the Center of Disease Control and Prevention (CDC), together with low variability among the blind duplicates, suggests that both methods reported here would be suitable for the analysis of urinary AM as a biomarker for human exposure of atrazine. PMID- 17723477 TI - Analysis of Strychnos alkaloids in traditional Chinese medicines with improved sensitivity by sweeping micellar electrokinetic chromatography. AB - The application of an on-line sweeping preconcentration method in micellar electrokinetic chromatography (MEKC) for the determination of Strychnos alkaloids, namely strychnine and brucine, has been investigated in this work. After experimental optimizations, the best separation was achieved in 50 mmol l( 1) H3PO4 (pH 2.0) containing 100 mmol l(-1) SDS and acetonitrile in a ratio of 4:1 (v/v), with an applied voltage of -20 kV at 20 degrees C. The sample matrix consisted of 100 mmol l(-1) H3PO4 (pH 2.0), and sample introduction was performed at 0.5 psi for 270 s, with photodiode array detection at 203 nm. Compared with the conventional MEKC injection method, up to 100-fold improvement in concentration sensitivity was achieved in terms of peak height by using this sweeping injection technique. In the method, the compound berberine was used as the internal standard for the improvement of the experimental reproducibility. The calibration curve was linear over a range of 0.5-15 microg ml(-1) for both strychnine and brucine, with a correlation coefficient of 0.998 and 0.997, respectively. The detection limits (S/N=3:1) for strychnine and brucine were 0.05 and 0.07 microg ml(-1), respectively. The sweeping-MEKC method has been successfully applied to the analysis of strychnine and brucine in Strychnos nux vomica L. and its Chinese medicinal preparations. PMID- 17723478 TI - A novel monolithic column for capillary electrochromatographic separation of oligopeptides. AB - A monolithic column was prepared using l-phenylalanine as template and a covalent approach through the formation of Schiff base with o-phthalaldehyde (OPA). OPA, allylmercaptan, l-phenylalanine, and triethylamine were stirred at first, then methacrylic acid, 2-vinylpyridine, ethyleneglycol dimethacrylate, alpha,alpha azobisisobutyronitrile, and 1-propanol were added to the reaction mixture. The resulting material was introduced into a capillary column. Following thermal polymerization, the template was then extracted with a mixture of HCl and methanol. The column was employed for the capillary electrochromatographic separation of oligopeptides. A capillary column of 75 (50) cm x 75 microm ID with a mobile phase of phosphate buffer (pH 7.0, 40 mM)/methanol (5%, v/v), an applied voltage of +15 kV, and detection at 214 nm, could baseline separate angiotensin I, angiotensin II, [Sar1, Thr8] angiotensin, oxytocin, vasopressin, tocinoic acid, beta-casomorphin bovine, beta-casomorphin human, and FMRF amide within 20 min. The separation behavior of the templated polymer was also compared with that of the non-templated polymer. As a result, it can be concluded that the electrochromatographic separation of this set of peptides was mediated by a combination of electrophoretic migration and chromatographic retention involving hydrophobic, hydrogen bonding, electrostatic as well as the Schiff base formation with OPA in the cavity of the templated polymer. PMID- 17723479 TI - Ultraviolet absorbance detection of colchicine and related alkaloids on a capillary electrophoresis microchip. AB - The separation and UV absorbance detection of four toxic alkaloids, colchicine, thiocolchicine, colchicoside, and thiocolchicoside, on a microchip-based capillary electrophoresis device are reported. To increase the sensitivity of UV absorbance detection, optical cells with extended path lengths were integrated into the separation channel during the microfabrication process. The absorbance values realized on the microchip using these optical cells were proportional to the increase in average depths according to the Beer-Lambert Law, resulting in sensitivity enhancements by as much as five times. Linearity of response was observed from 5.0 to 500 mg L(-1) of colchicine, with detection limits ranging from 2 to 6 mg L(-1) depending upon the specific alkaloid and the dimension of the optical cell. The extraction of colchicine from spiked milk samples was performed and an average recovery rate of 83% with a relative standard deviation of 3.8% was determined using the optimized conditions on the microchip. PMID- 17723480 TI - Characterization and application of a new ultraviolet derivatization reagent for amino acids analysis in capillary electrophoresis. AB - A new ultraviolet (UV) labeling reagent, p-acetamidobenzenesulfonyl fluoride (PAABS-F), was designed and synthesized to label and determine the amino acids by capillary electrophoresis (CE) with diode-array detector (DAD). PAABS-F is very stable and easy to synthesize. It reacted with primary or secondary amino acids very quickly under facile conditions to give corresponding derivatives in high yield with excellent sensitivity and stability. No by-products were observed in amino acid derivatives when stored at room temperature under natural daylight for at least 7 days. Both amino acids standard solution and real samples reacted with this new UV labeling reagent smoothly to form high UV-absorption derivatives. The labeled 20 standard amino acids were efficiently separated by CE and the mass detection limits (S/N=3) were ranged from 59.3 fmol for L-tryptophan to 1.70 pmol for L-histidine. PMID- 17723481 TI - Puff-by-puff resolved characterisation of cigarette mainstream smoke by single photon ionisation (SPI)-time-of-flight mass spectrometry (TOFMS): comparison of the 2R4F research cigarette and pure Burley, Virginia, Oriental and Maryland tobacco cigarettes. AB - Soft single photon ionisation (SPI)-time-of-flight mass spectrometry (TOFMS) is applied for the characterisation and comparison of puff-by-puff resolved and total yields of cigarette mainstream smoke from single tobacco type cigarettes (Virginia, Oriental, Burley, and Maryland) and the 2R4F University of Kentucky research cigarette. Puff-by-puff characteristics of various smoke components within one cigarette type as well as between different cigarette types can differ tremendously. This is demonstrated by means of a few selected compounds. Puff yields vary between 15 and 106 microm for acetaldehyde, 6 and 57 microm for NO, and between 1 and 8 microm for butadiene. Thereby, cigarettes containing 100% Oriental and Burley tobacco exhibit a very unique behaviour for the first and last puff. Different cultivation and processing methods as well as burning characteristics are most likely responsible for this. Since the 2R4F cigarette contains all four tobacco types it combines features of all of them. However, for some smoke constituents, smoking of the 2R4F reference cigarette results in exceptionally high yields which might not be attributable to the four pure tobacco types, but to other factors. In addition, comparison of the different cigarettes was also carried out by normalising the yields to puff resolved particulate matter. This procedure minimises effects caused by unequal smoke formation and represents another approach in evaluating the data. PMID- 17723482 TI - Identification of C-21 steroidal glycosides from the roots of Cynanchum chekiangense by high-performance liquid chromatography/tandem mass spectrometry. AB - High-performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC/ESI-MS/MS) was used to identify C-21 steroidal glycosides with immunological activities in roots of Cynanchum chekiangense. In the MS/MS spectra, fragmentation reactions of the [M+Na]+ were recorded to provide structural information about the glycosyl and aglycone moieties. To further confirm the fragments structures, off-line Fourier transform ion cyclotron resonance tandem mass spectrometry (FT-ICR-MS/MS) was also performed. In the study, four known steroidal glycosides cynascyroside C, chekiangensosides A and B, glaucoside H, and four novel steroidal glycosides chekiangensosides C, D, E and chekiangensoside A isomer were identified based on mass spectral data, NMR spectral data and standards. This is the first report on identifying steroidal glycosides in roots of C. chekiangense by HPLC/ESI-MS/MS directly, which could save time and material consuming efforts in traditional phytochemistry analysis. PMID- 17723483 TI - Stability-indicating high-performance thin-layer chromatographic determination of levonorgestrel and ethinyloestradiol in bulk drug and in low-dosage oral contraceptives. AB - A stability-indicating high-performance thin-layer chromatography (HPTLC) method was developed and validated for simultaneous determination of steroidal hormones levonorgestrel and ethinyloestradiol both in bulk drug and in low-dosage oral contraceptives. Optimization of conditions for the spectrodensitometric procedure was reached by eluting HPTLC silica gel plates in a 10 cm x 10 cm horizontal chamber. The solvent system consisted of hexane-chloroform-methanol (1.0:3.0:0.25, v/v/v). This system was found to give compact, dense and typical peaks for both levonorgestrel (R(f)=0.65+/-0.03) and ethinyloestradiol (R(f)=0.43+/-0.02). Densitometric analysis of the drugs was carried out in the reflectance mode at 225 nm by using a computer controlled densitometric scanner. The calibration curves of levonorgestrel and ethinyloestradiol were linear in the range of 200-800 and 40-160 ng per spot, respectively. The method was validated for precision, robustness and recovery. As the proposed method can effectively separate the drugs from their degradation products, it can be employed as a stability-indicating method. PMID- 17723484 TI - Cross-sensitive rare-earth metal sensors based on bidentate neutral organophosphorus compounds and chlorinated cobalt dicarbollide. AB - A variety of new chemical sensors (ion selective electrodes) for determination of rare-earth (RE) and trivalent metal cations such as yttrium(III), lanthanum(III), praseodymium(III), neodymium(III) and europium(III) that are commonly present in aqueous radiological samples, e.g. in high-level liquid waste (HLW) and solutions from reprocessing spent nuclear fuel, have been developed and studied. The sensors are based on bidentate neutral organophosphorus compounds, such as methylene bridged diphosphine dioxides and carbamoylmethylphosphine oxides, which are efficient extractants, especially when used in conjunction with chlorinated cobalt dicarbollide, for recovery and concentration of the RE and actinide elements from acidic HLW derived from the nuclear fuel cycle. The sensors exhibit remarkable sensitivity to RE cations and indicate promise for HLW analysis. PMID- 17723485 TI - Application of SiO2-poly(dimethylsiloxane) hybrid material in the fabrication of amperometric biosensor. AB - Silica xerogel was widely used in the development of biosensors by coupling the desired biological components to various transducers. Unfortunately, the application of xerogels is limited due to their poor mechanical properties and poor structural maintenance of entrapped biomaterials. In this study, the availability of poly(dimethylsiloxane) (PDMS)-modified silica sol-gel (TEOS/PDMS Ormosil) glass in the immobilization of enzymes and its application in the fabrication of amperometric biosensor was investigated. We demonstrated that most of activity of encapsulated horseradish peroxidase can be preserved in PDMS modified SiO2 glass compared with conventional silica xerogel. The synthesized monoliths exhibited high transparency and crack-free. The enzyme electrode based on glucose oxidase encapsulated TEOS/PDMS Ormosil glass on Pd electrode was fabricated and characterized electrochemically. The characteristics of the biosensor were studied by cyclic voltammetry and chronoamperometry. The biosensor exhibited a series of good properties: high sensitivity (1.63 microA mM(-1) analyte), short response time and high reproducibility. The results indicate that TEOS/PDMS Ormosil glass has great potential to the immobilization of biomaterials as well as the fabrication of biosensors. PMID- 17723486 TI - Voltammetric determination of boron by using Alizarin Red S. AB - A novel voltammetric method for boron determination in ppb level is described. Boron complexes with Alizarin Red S (ARS) and the complex, as well as the free ligand, both adsorbs on a hanging mercury drop electrode. The method is based on the monitoring the anodic peak of the complex at -0.47 V in ammonium acetate phosphate buffer (pH 7). The maximum peak current was obtained by scanning the potential from -700 mV versus Ag/AgCl to more positive potentials without accumulation in the presence of 1 x 10(-6) mol L(-1) of ARS. The instrumental parameters were mainly differential pulse mode with a pulse duration of 0.02 s and a scan rate of 5 mV s(-1). The limit of detection based on signal to ratio of 3 was calculated as 15 microgL(-1). The calibration plot for boron was linear in the range of 0-500 microg L(-1). The interference of various ions was examined and serious interference was observed from antimony(III). The relative standard deviation was found to be 5.1% for the 100 microg L(-1) boron level (n=10). The method was applied to the determination of boron in water and seawater samples with high boron content. The results obtained from the developed method were compared with Azomethine-H-method and no statistically significant difference was found. PMID- 17723487 TI - Examination of n=2 reaction mechanisms that reproduce pH-dependent reduction potentials. AB - Flavo- and quinoproteins often exhibit trends in reduction potentials that approximate -30 mV per pH unit. At least five different reaction mechanisms can model the behavior described by the following Nernst equation: E(observed)=E0'+(0.059/2) log [H+]. The pH-reduction potential profile described by this equation can be reproduced by various models using different reaction mechanisms, and these mechanisms yield different reduction potentials and acid dissociation constants. In order to understand these discrepancies, this article discusses how the various methods reproduce this pH-dependent Nernst equation. PMID- 17723488 TI - Variable selection for discriminating herbal medicines with chromatographic fingerprints. AB - When discriminating herbal medicines with pattern recognition based on chromatographic fingerprints, typically, the majority of variables/data points contain no discrimination information. In this paper, chemometric approaches concerning forward selection and key set factor analysis using principal component analysis (PCA), unweighted and weighted methods based on the inner- and outer-variances, Fisher coefficient from the between- and within-class variations were investigated to extract representative variables. The number of variables retained was determined based on the cumulative variance percent of principal components, the ratio of observations to variables and the factor indicative function (IND). In order to assess the methods for variable selection and criteria levels to determine the number of variables retained, the original and reduced datasets were compared with Procrustes analysis and a weighted measure of similarity. Moreover, the tri-variate plots of the first three PCA scores were used to visually examine the reduced datasets in low dimensional space. Herbal samples were finally discriminated by use of Bayes discrimination analysis with the reduced subsets. The case study for 79 herbal samples showed that, the methods of forward selection associating the variables with the loadings closest to 0 and key set factor analysis were preferable to determine the representative variables. Procrustes analysis and the weighted measure were not indicative to extract representative variables. High matching between the original and reduced datasets did not suggest high prediction accuracy. Visually examining the PC1-PC2 PC3 scores projection plots with the reduced subsets, not all the herb samples could be separated due to the complexity of chromatographic fingerprints. PMID- 17723489 TI - Classification study of skin sensitizers based on support vector machine and linear discriminant analysis. AB - The support vector machine (SVM), recently developed from machine learning community, was used to develop a nonlinear binary classification model of skin sensitization for a diverse set of 131 organic compounds. Six descriptors were selected by stepwise forward discriminant analysis (LDA) from a diverse set of molecular descriptors calculated from molecular structures alone. These six descriptors could reflect the mechanic relevance to skin sensitization and were used as inputs of the SVM model. The nonlinear model developed from SVM algorithm outperformed LDA, which indicated that SVM model was more reliable in the recognition of skin sensitizers. The proposed method is very useful for the classification of skin sensitizers, and can also be extended in other QSAR investigation. PMID- 17723490 TI - Resonance Rayleigh scattering study on the interaction of gold nanoparticles with berberine hydrochloride and its analytical application. AB - The interaction of gold nanoparticles with berberine hydrochloride has been studied by using resonance Rayleigh scattering (RRS) spectra. In pH 3.8-5.5 aqueous solution, citrate acid ([H2L2-]) self-assembled on the surface of positively charged gold nanoparticles (average diameter is about 12.0 nm) to form a supermolecular complex with negative charges. By virtue of electrostatic attraction, hydrophobic force and charge transfer, the complex bound with berberine to form complex, which had bigger diameter (35 nm) than gold nanoparticles. The formation of the binding production not only resulted in the red shift of absorption of gold nanoparticles from 518 to 672 nm, but also led to the greatly enhancement of RRS intensity. At the same time, the intensities of second-order scattering (SOS) and frequency-doubling scattering (FDS) were also increased. Under definite condition, the increment of the RRS (DeltaI) were proportional to the concentration of berberine. A sensitive and simple method for the determination of berberine based on the RRS technique has been developed. The detection limit (3sigma) for berberine was 0.40 ng mL(-1) and the quantitative determination range was 1.33-240 ng mL(-1). In this work, the optimum conditions of reaction, the effect of foreign substances and the analytical application had been investigated. PMID- 17723491 TI - Sonoelectrochemical synthesis of spike-like gold-silver alloy nanoparticles from bulk substrates and the application on surface-enhanced Raman scattering. AB - The synthesis of non-spherical spike-like gold-silver alloy nanoparticles on platinum substrates was first developed by sonoelectrochemical methods in this study. First, a silver substrate was roughened by a triangular-wave oxidation reduction cycle (ORC) in an aqueous solution containing 0.1 M HCl. Silver containing complexes were found in the solution after the ORC treatment. Then a gold substrate was subsequently roughened by the similar ORC treatment in the same silver complexes-containing solution. After this procedure, Au- and Ag containing complexes were left in the solution. Subsequently, the Au working electrode was immediately replaced by a Pt electrode. A cathodic overpotential was applied under controlled sonication and slight stirring to synthesize Au-Ag alloy nanoparticles on the Pt substrate. Encouragingly, the surface-enhanced Raman scattering (SERS) of Rhodamine 6G on the Au-Ag alloy nanoparticles deposited Pt substrate exhibits a higher intensity by eight-fold of magnitude and a better resolution, as compared to that obtained on the Au nanoparticles deposited Pt substrate. PMID- 17723492 TI - Novel self-protective phosphorescence from crystalline nanoparticles assembled by 3-bromo- and 3-iodo-carbazoles based on halogen-halogen interaction in suspension solutions. AB - The crystalline nanoparticles can be assembled by 3-bromo- and 3-iodo-carbazole (3-BrC and 3-IC) based on the halogen-halogen interaction in suspension aqueous solutions. As the colloid-like suspension was dropped onto film the particles further aggregate as rod-like structures with size of 3 microm in length and 1 microm in width. The halogen-halogen interaction are well proved by single crystal X-ray data, and the data reveal that each bromine atom interacts with the neighboring two, and each iodine atom interacts with the neighboring five and I-I interaction is stronger than that of Br-Br. Both 3-BrC and 3-IC can emit novel self-protective room temperature phosphorescence (RTP) in the range of 480 to near 800 nm at the excitation of 338 nm, and 3-BrC shows additionally the delayed fluorescence emission from 350 to 480 nm, both possessing the charge-transfer character caused by halogenations. RTP decay possesses the bi-exponential property and RTP lifetimes are 3.37, 31.16 ms (with ethanol) and 1.52, 30.83 ms (with THF) for 3-BrC or 3.53, 14.95 ms (with ethanol) and 1.68 ms, 13.74 ms (with THF) for 3-IC, showing " heavier atom ", I, makes intersystem crossing rate k(ISC) from both S1 to T1 and T1 to S(0) faster. For the results, the detection limits of 3-BrC and 3-IC can reach 2.4 x 10(-7) and 9.0 x 10(-8)mol L(-1), respectively, with wider linear range and higher precision compared with other systems. PMID- 17723493 TI - Palladium and the electrochemical quartz crystal microbalance: a new method for the in situ analysis of the precious metal in aqueous solutions. AB - A new method for the quantitative determination of palladium(II) by the electrochemical quartz crystal microbalance (EQCM) technique has been developed. Using a bare carbon-coated quartz crystal, Pd(II) ions are directly deposited from aqueous solution as palladium metal onto the crystal surface, and the Pd(II) concentration is determined with a detection limit of 0.0156 mM, or 1.66 ppm. No complexing agent or preconcentration of palladium is required for the analysis. The palladium is stripped from the crystal through its electrochemical oxidation, regenerating the crystal for subsequent multi-cycle palladium analyses. A conventional gold-coated quartz crystal was incapable of carrying out the same measurements. The EQCM technique presented is simple, sensitive, and reproducible for the detection of this widely used precious metal. PMID- 17723494 TI - A comprehensive immunoassay for the detection of microcystins in waters based on polyclonal antibodies. AB - Microcystins (MCs) are a group of closely related toxic cyclic heptapeptides produced by common cyanobacteria (blue-green algae), and microcystin-leucine arginine (MC-LR) is among the most frequent and most toxic microcystin congeners. In this study, a free amino group was introduced to MC-LR at its seventh amino acid residue with 2-mercaptoethylamine, and the product aminoethyl-MC-LR was coupled to bovine serum albumin (BSA) and horseradish peroxidise (HRP) by glutaraldehyde to be complete antigen (MC-LR-BSA) and labelled hapten (MC-LR HRP), respectively. Polyclonal antibodies against MC-LR were generated by immunization with MC-LR-BSA. A direct competitive enzyme-linked immunosorbent assay (dc-ELISA) was established to detect the MCs in waters, which showed a good cross-reactivity with MC-LR, MC-RR, MC-YR, MC-LF, MC-LW and nodularin, and have a detection limit for MC-LR 0.12 microg L(-1), the 50% inhibition concentration (IC50) for MC-LR was 0.63+/-0.06 microg L(-1) and the quantitative detection range was from 0.17 to 2.32 microg L(-1), the analysis result of water samples showed good recovery and reliability. So the comprehensive and reliable dc-ELISA will well potentially suit for sensitive analysis for total MCs in drinking as well as resource water samples. PMID- 17723495 TI - A novel flow-based strategy for implementing differential kinetic analysis. AB - Differential kinetic analysis can be implemented in a multi-pumping flow system, and this was demonstrated in relation to an improved spectrophotometric catalytic determination of iron and vanadium in Fe-V alloys. The method exploited the influence of Fe(II) and V(IV) on the rate of iodide oxidation by Cr(VI) under acidic conditions; therefore the Jones reductor was needed. The sample was inserted into an acidic KI stream that acted also as carrier stream, and a Cr(VI) solution was added by confluence. Successive measurements were performed during sample passage through the detector, each one related to a different yet reproducible condition for reaction development. Data treatment involved multivariate calibration by the PLS algorithm. The proposed system is very simple and rugged, allowing about 50 samples to be run per hour, meaning 48 mg KI per determination. The first two latent variables carry ca. 94% of the analytical information, pointing out that the intrinsic dimensionality of the data set is two. Results are in agreement with inductively coupled argon plasma-optical emission spectrometry. PMID- 17723498 TI - Metal oxide thin films as sensing layers for ozone detection. AB - In2O3-x thin films with a thickness of 100-990 nm were grown by dc magnetron sputtering. Their structural, electrical and ozone sensing properties were analyzed. Structural investigations carried out by electron probe micro analysis, secondary ion mass spectrometry and atomic force microscopy showed a strong correlation between stoichiometry, surface topology and gas sensitivity. Moreover, the electrical conductivity of In2O3-x thin films exhibited a change of over six orders of magnitude during photoreduction with ultraviolet light and subsequent oxidation in ozone atmosphere at room temperature. PMID- 17723497 TI - pH-sensitive diamond field-effect transistors (FETs) with directly aminated channel surface. AB - We have introduced pH sensors fabricated on diamond thin films through modification of the surface-terminated atom. We directly modified the diamond surface from hydrogen to amine or oxygen with ultraviolet (UV) irradiation under ammonia gas. The quantified amine site based on the spectra obtained by X-ray photoelectron spectroscopy (XPS) is 26% (2.6 x 10(14) cm(-2)) with UV irradiation for 8h and its coverage is dependent on the UV irradiation time. This directly aminated diamond surface is stable with long-term exposure in air and electrolyte solution. We fabricated diamond solution-gate field-effect transistors (SGFETs) without insulating layers on the channel surface. These diamond SGFETs with amine modified by direct amination are sensitive to pH (45 mV/pH) over a wide range from pH 2 to 12 and their sensitivity is dependent on the density of binding sites corresponding to UV irradiation time on the channel surface. PMID- 17723499 TI - Determination of labile trace metals with screen-printed electrode modified by a crown-ether based membrane. AB - In this work, we have undertaken the construction of a screen-printed electrode modified by a specific membrane to protect the working surface from interferences during the analysis of trace metals by anodic stripping voltammetry. Different crown-ethers selected for their metals affinity have been incorporated into a membrane then deposed on the working surface of the electrode. Each modified electrode has been first tested in an acidified KNO3 10(-1) mol L(-1) solution (pH 2) doped by free Cd2+ and Pb2+ ions. The response and selectivity of the modified electrodes have been investigated according to different parameters: (i) the substrates (commercial ink or carbon based homemade ink), (ii) the electrode support (polystyrene or transparency film) and (iii) crown-ethers nature (dibenzo 24-crown-8 and tetrathiacyclododecane 12-crown-4). The influence of the substrate on the response of the electrode is clearly demonstrated. Homemade ink appears as the most appropriate substrate to modify the working surface of the screen printed electrode by a crown-ether based membrane. The effect of the composition of the membrane has been shown too. The best membrane developed showed a detection limit of 0.6 x 10(-8) mol L(-1) for Cd and 0.8 x 10(-8) mol L(-1) for Pb and a quantification limit of 10(-8) mol L(-1) for Cd and 2 x 10(-8) mol L(-1) for Pb. This method, which integrates the extraction, preconcentration and measurement, was successfully applied to environmental samples without pretreatment. PMID- 17723500 TI - Electropolymerization and characterization of polyaniline films using a spectroelectrochemical flow cell. AB - A new spectroelectrochemical flow cell is presented and its capability to provide a better understanding of reaction mechanisms is illustrated with the study of the electrosynthesis and characterization of a conducting polymer, polyaniline (PANI). A spectroelectrochemical study of electropolymerization of aniline under flow conditions has been performed for the first time. The significant influence that the flow rate of feeding monomer solution has on the electropolymerization process and, consequently, on the electrochromic properties of the resulting polymer has been demonstrated. PMID- 17723501 TI - Preparation and characterization of diethylene glycol bis(2-aminophenyl) ether modified glassy carbon electrode. AB - Diethylene glycol bis(2-aminophenyl) ether (DGAE) diazonium salt was covalently electrografted on a glassy carbon (GC) surface and behavior of this novel surface was investigated. Synthesis of DGAE diazonium salt (DGAE-DAS) and in situ modification of GC electrode were performed in aqueous media containing NaNO2, keeping the temperature below +4 degrees C. For the characterization of the modified electrode surface by cyclic voltammetry, dopamine (DA) was used to prove the attachment of the DGAE-DAS on the GC surface. Raman spectroscopy and electrochemical impedance spectroscopy (EIS) were used to observe the molecular bound properties of the adsorbates at the DGAE-modified GC surface (GC-DGAE). The EIS results were analyzed using the Randles equivalent circuit. The charge transfer resistance on bare GC and the modified surface were calculated using the model equivalent circuit for the ferrocene redox system. Surface coverage was found as 0.4 showing the presence of high pinhole and defects in the modified electrode. The rate constant of electron transfer through the monolayer was calculated for ferrocene. Working potential range and the stability of the DGAE modified GC electrode was also determined. PMID- 17723502 TI - New real-time analytical applications of electrochemical quartz crystal microbalance Stoichiometry and phase composition monitoring of electrodeposited thin chalcogenide films. AB - The electrochemical quartz crystal microbalance (EQCM) has recently gained increasing popularity as a powerful tool for electrochemical interface examinations. This paper reports on its great potential for developing new real time analytical protocols. Potentiostatic coulometry is used in conjunction with quartz crystal microgravimetry (QCMg) with controlled hydrodynamics to develop two new analytical procedures: real-time stoichiometry monitoring of electrodeposited binary chalcogenide films and phase composition quantification of electrodeposited ternary chalcogenide compounds. The newly developed EQCM methods are illustrated on the examples of Ag2+deltaSe-electrodeposited films and the electroformation of ternary CuAgSe-films. Both compounds have been successfully used as ion-selective membranes for flow-injection detectors. The experimental set-up including hydrodynamic control, the main strategy of the approach used and its scope and limitations are broadly discussed. The obtained data allow for real time profile monitoring of either stoichiometry (Ag2+deltaSe case) or phase composition (CuAgSe-case). PMID- 17723503 TI - Application of electrochemical optical waveguide lightmode spectroscopy for studying the effect of different stress factors on lactic acid bacteria. AB - Electrochemical optical waveguide lightmode spectroscopy (EC-OWLS) has been developed to combine evanescent-field optical sensing with electrochemical control of surface adsorption processes. For bioanalytical sensing, a layer of indium tin oxide (ITO) served as both a high-refractive index waveguide and a conductive electrode. In addition, an electrochemical flow-through fluid cuvette was applied, which incorporated working, reference, and counter electrodes, and was compatible with the constraints of optical sensing. The subject of our study was to monitor how the different stress factors (lactic acid, acetic acid and hydrogen peroxide) influence the survival of lactic acid bacteria. The advantage of EC-OWLS technique is that we could carry out kinetic studies on the behaviour of bacteria under stress conditions, and after exposure of lactobacilli to acid and oxidative stress we get faster results about the status of bacteria compared to the traditional quantitative methods. After optimization of the polarization potential used, calibration curve was determined and the sensor response of different rate of living and damaged cells was studied. The bacterial cells were adsorbed in native form on the surface of the sensor by ensuring polarizing potential (1V) and were exposed to different concentration of acetic acid and hydrogen peroxide solution to 1h, respectively and the behaviour of bacteria was monitored. Results were compared to traditional micro-assay method. PMID- 17723504 TI - Continuous oxygen monitoring in subcutaneous adipose tissue using microdialysis. AB - A measurement system, consisting of an optochemical glass capillary oxygen sensor, an optoelectronic measuring unit and a microdialysis catheter (CMA 60) for the extraction of the biological fluid from the subcutaneous adipose tissue of critically ill patients is reported. The capillary sensor is based on the oxygen sensitive dye platinum (II) meso-tetra(pentafluorophenyl) porphyrin (Pt TFPP) incorporated in a polystyrene matrix. The measuring system has been tested in vitro and in vivo. In particular in vitro long-term stability of the sensor has been investigated in different measurement media (elomel, 5% mannitol, Ringer, dialysed blood). The influence of different flow rates from 0.1 up to 7.0 microl min(-1) on the sensor response as well as the oxygen recovery rate are discussed. The presented measurement system allows the measurement of oxygen in biological fluid in the range from 0 to 300 mmHg, with a resolution better than 1 mmHg and high accuracy (better than +/-1 mmHg absolute). Finally, the suitability of the described measurement system for the continuous oxygen monitoring in subcutaneous adipose tissue has been proved in in vivo investigations performed on test animals. PMID- 17723505 TI - Luminescence lifetime-based carbon dioxide optical sensor for clinical applications. AB - The development of both an optical planar and capillary based carbon dioxide sensor, which final aim is pCO2 monitoring in adipose tissue of critically ill patients, is reported. The sensor is based on the measuring principle of phase fluorometry using a dual luminophore referencing scheme (DLR) to convert the CO2 dependent intensity signal into phase domain. The CO2 sensors have been prepared by incorporating two appropriate luminophores and a phase transfer agent in a same hydrophobic polymer as matrix. The short-lifetime luminophore used as pH indicator is 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS). The second inert luminophore is the long-lifetime dye Ruthenium(II) tris(4,7-diphenyl 1,10-phenanthroline) (Ru(dpp)3(2+)), which has been made insensitive to oxygen by immobilising in a suitable oxygen impermeable polymer. As phase transfer agent, tetraoctylammonium hydroxide (TOA-OH) has been chosen. Both sensor types have been characterised with respect to optimise sensitivity and mechanical stability. For this purpose, several polymers, such as ethylcellulose, eudragit RL100 (EG), copolymer eudragit/poly(ethylene glycol) (PEG) and silicone have been examined as appropriate matrix for incorporation of two indicators. The largest phase shift up to 13 degrees and 15 degrees has been observed in the case of silicone and copolymer EG/PEG, respectively, and they have been in detail examined in terms of sensitivity and stability. The presented sensors enable the measurement of pCO2 in the range from 0 to 150 mmHg, with a resolution of 0.5 mmHg and an accuracy of +/-1 mmHg absolute or less than 7% of the read-out value. All measurements have been carried out only in aqueous solutions before clinical measurements. PMID- 17723506 TI - Comparison of antibody and aptamer receptors for the specific detection of thrombin with a nanometer gap-sized impedance biosensor. AB - Nanogap-impedance biosensors with electrode separations of 75 nm have been fabricated by means of standard optical lithography and a sacrificial layer technique. Due to a large surface-to-volume ratio and high sensitivity, these sensors are superior compared to open interdigitated electrode structures. As a model, the blood coagulation factor thrombin was detected. As specific receptors, either an antibody or a RNA-aptamer have been used. The microwave frequency impedance measurements showed that both ligands were equally suitable for the specific detection of thrombin. PMID- 17723507 TI - Bioelectronic sniffer for nicotine using enzyme inhibition. AB - A novel bioelectronic sniffer for nicotine in the gas phase was developed with enzyme inhibition principle to butyrylcholinesterase activity. The bioelectronic devices for nicotine in the gas and liquid phases were constructed using a Clark type dissolved oxygen electrode and a membrane immobilized butyrylcholinesterase and choline oxidase. After the assessment of the sensor performances to choline and butyrylcholine as pre-examinations, the characteristics of the biosensor and bio-sniffer for nicotine were evaluated in the liquid and gas phases, respectively. The sensor signal of the bio-devices with 300 micromol l(-1) of butyrylcholine decreased quickly following application of nicotine and reached to the steady-state current, thus relating the concentration of nicotine in the liquid and gas phases. The biosensor was used to measure nicotine solution from 10 to 300 micromol l(-1). In the gas-phase experiment, the current signal of the bio-sniffer was also found to be linearly to the nicotine concentration over the range of 10.0-1000 ppb including 75.0 ppb as threshold limit value (TLV) by American Conference of Governmental Industrial Hygienists (ACGIH). PMID- 17723509 TI - Deoxyribonucleic acid (DNA) biosensors for environmental risk assessment and drug studies. AB - In the present work, electrochemical DNA biosensors are proposed as a screening device for the rapid bio-analysis of environmental pollution and DNA-drug interaction studies. The binding of small molecules to DNA immobilised on disposable screen-printed electrodes has been measured through the variation of the electrochemical signal of guanine by square wave voltammetric scans. These kinds of biosensors were used to evaluate the soil contamination level in an Italian polluted area and the results were compared with several methods for the DNA damage detection, as Comet genotoxicity effects, aberrant anatelophases and micronucleated cells frequency on plant roots, and with fixed wavelength fluorescence (FF) by using 2-aminoanthracene as standard compound. The results showed the ability of the biosensors to distinguish in 11 min low, medium and high contaminated soils with good correlation with well established techniques as well as FF, Comet and genotoxicity tests. The same kind of biosensors was also used to evaluate the interaction of DNA with some anti-proliferative metallo drugs, and the electrochemical responses reflected the kind of interaction. The reproducibility of the electrochemical measurements of DNA guanine peak was estimated as less than 10% of relative standard deviation (R.S.D.%). PMID- 17723508 TI - Optical bio-sniffer for methyl mercaptan in halitosis. AB - An optical bio-sniffer for methyl mercaptan (MM) one of major odorous chemicals in halitosis (bad breath) was constructed by immobilizing monoamine oxidase type A (MAO-A) onto a tip of a fiber optic oxygen sensor (od: 1.59 mm) with an oxygen sensitive ruthenium organic complex (excitation: 470 nm, fluorescent: 600 nm). A flow cell for circulating buffer solution was applied to rinse and clean the tip of the device like nasal mucosa. In order to amplify the bio-sniffer output, a substrate regeneration cycle caused by coupling MAO-A with l-ascorbic acid (AsA) as reducing reaction with reagent system was applied to the sensor system. After evaluating the sensor characteristics using a gas flow measurement system with a gas generator, the optical bio-sniffer was applied to expired gases from healthy male volunteers for halitosis analysis as a physiological application. The optical bio-sniffer was applied to detect the oxygen consumption induced by MAO-A enzymatic reaction (and AsA chemical reduction) with gaseous MM application. The bio-sniffer was calibrated against MM vapor from 8.7 to 11500 ppb with correlation coefficient of 0.977, including a MM threshold (200 ppb) of pathologic halitosis and the human sense of smell level 3.5 (10.0 ppb), with good gas-selectivity based on the MAO-A substrate specificity. As the result of the physiological application, the optical bio-sniffer could successfully monitor the MM level change in breath samples during daytime, which is consistent with the previously reported results. PMID- 17723511 TI - A Mach-Zehnder interferometer based on silicon oxides for biosensor applications. AB - Integrated optical devices have been increasingly interested in biosensor applications including environmental pollution, biological process and medical diagnostics. Integrated optics allows high-detection sensitivity to be achieved using optical transduction techniques in a microfluidic format. Among different transduction techniques, a Mach-Zehnder interferometer (MZI) has advantage of its inherent high sensitivity and accuracy. The evanescent wave of an optical waveguide interacts with an adjacent layer, and this can be the basis of the recognition of biomolecules. In recent years, silicon dielectrics as potential materials have been attracted in an integrated optics. The refractive index of these silicon-based materials can be easily adjusted continuously over a wide range between 1.45 (SiO2) and 1.97 (SiO). This comes to be very attractive in terms of design and fabrication of single-mode waveguides. In this article, we tried to realize the Mach-Zehnder interferometer sensor based on silicon oxides, and the refractive index of the oxides was controlled by the oxygen concentration to achieve the single-mode behavior of a total internal reflection (TIR) waveguide. We have performed to verify the feasibility of the MZI sensor for the direct detection of immunoreactions. PMID- 17723510 TI - Application of "membrane-engineering" to bioelectric recognition cell sensors for the ultra-sensitive detection of superoxide radical: a novel biosensor principle. AB - A new, hybrid type of ultra-sensitive electrophysiological superoxide anion (O2* ) sensor is described, which is based on "membrane-engineered" mammalian cells immobilized in an alginate matrix. The membrane-engineering process involved the electroinsertion of superoxide dismutase (SOD) molecules in the membranes of Vero fibroblast cells, which acted as catalytic units able to convert O2*- to H2O2. Superoxide dismutation triggered changes to the cell membrane potential that were measured by appropriate microelectrodes, according to the principle of the bioelectric recognition assay (BERA). The sensor instantly responded to O2*- with a detection limit (S/N=3) of 100 pM. Combined with a 4-month storage capacity at room temperature, the novel biosensor principle offers new perspectives for monitoring ultra-low concentrations of free radical species and oxidative agents in biological systems. PMID- 17723512 TI - Structural development of a minimally invasive sensor chip for blood glucose monitoring. AB - Our newly developed glucose sensor chip has the world smallest blood sample volume, as small as 200 nL, which makes lancing with less pain possible. Forming the inside walls of the cavity, where the blood is collected, by screen printing of the adhesive ink instead of the conventional adhesive sheet placing drastically reduced the cavity thickness, to less than 50 microm, and the blood sample volume. On this thin-cavity type sensor, the cavity thickness was proven to have the strong influence on the sensor response. This means that thinner cavity requires more accurate printing, in terms of thickness control. The printing conditions were adjusted to minimize the dispersion in the cavity geometry. One of the challenges was how to print patterns without saddles, which was achieved by selecting proper ink. After the adjustment, the contribution of the dispersion in the cavity thickness and the electrode area to the dispersion in sensor responses was estimated, respectively, which indicated the contribution of the cavity thickness still existed. Finally, the sensor was evaluated using whole sheep blood containing glucose of from 60 to 493 mg dL(-1). Irrespective of the influence relating to the cavity thickness, the coefficients of variation of the sensor responses were from 4.4 to 7.6. In addition, the correlation curve showed linearity in this blood glucose range, and the coefficient of determination r2 was 0.98. That is, the sensor was verified to have sufficient performance for practical use. PMID- 17723513 TI - Highly selective microbiosensors for in vivo measurement of glucose, lactate and glutamate. AB - An alternative approach to production of amperometric microbiosensors, which combines electrochemical electrometallization and electropolymerisation of phenylene diamine film with covalent binding enzymes, is presented. In this respect, for a sensitive detection of hydrogen peroxide (HP) at +0.4V versus Ag/AgCl (detection limit of 0.5 microM, s/n=3), carbon fiber microelectrodes (30 microm in diameter and 500 microm long) were covered with ruthenium. To obtain a highly selective detection of HP, in the presence of different interfering compounds (ascorbic acid, uric acid, etc.), an additive semi-permeable polymer film was formed on the top of the ruthenium layer by electropolymerisation of m phenylene diamine (m-PD). The enzymatic selective layers were formed by covalent cross-linking the enzymes (glucose oxidase, lactate oxidase or glutamate oxidase) with BSA by glutaraldehyde in the presence of ascorbate oxidase. An additional polymeric layer based on polyurethane and Nafion was deposited on the top of the enzymatic membrane (glucose oxidase, lactate oxidase, or glutamate oxidase) in order to extend the dynamic range of biosensors up to 4mM for glucose (R=0.997; Y[nA]=-0.22+9.68x[glucose, mM]), 1.75mM for lactate (R=0.991; Y[nA]=0.43+15.36x[lactate, mM]) and 0.25 mM for glutamate (R=0.999; Y[nA]=0.02+29.14x[glutamate, mM]). The developed microbiosensors exhibited also negligible influences from interfering compounds at their physiological concentrations. Microbiosensors remained stable during 10h in a flow injection system at 36 degrees C and pH 7.4. The microbiosensors developed are now used in vivo and, as an example, we report here the data obtained with the glucose biosensor. PMID- 17723514 TI - A needle-type optical enzyme sensor system for determining glucose levels in fish blood. AB - A needle-type biosensor system was developed for rapid and simple determination of glucose levels in fish blood. The sensor comprises a needle-type hollow container (18-gauge needle), immobilized enzyme membrane and optic fiber probe with ruthenium complex. The enzyme membrane was prepared from glucose oxidase, azide-unit pendant water-soluble photopolymer and an ultra-thin dialysis membrane. The optic fiber probe was inserted into the rolled enzyme membrane placed in the needle-type hollow container. The calibration curve was linear for glucose levels in fish plasma. One assay was completed within 3 min. A good reproducibility was observed for 60 times without exchange of the enzyme membrane. The sensor was inserted into the caudal vein of fish to measure blood glucose levels. The sensor responded immediately after insertion and glucose levels could be monitored. Good correlations were observed between values determined using the sensor and conventional methods in the range of 48-157 mg dl(-l) (correlation coefficient, 0.9474). PMID- 17723515 TI - Enzymatic methods in food analysis: determination of ascorbic acid. AB - The feasibility and expediency of enzymatic methods application in food analysis is demonstrated by the example of ascorbic acid (AsA) determination in foods. Enzymatic determination of ascorbic acid is based on its action as a second substrate of horseradish (HRP) and peanut (PNP) peroxidases in the reactions of o dianisidine (OD) and 3,3',5,5'-tetramethylbenzidine (TMB) oxidation with hydrogen peroxide. The rates of the reactions are monitored spectrophotometrically by measuring the duration of the induction period on kinetic curves plotted in coordinates absorption-time. The proposed procedures are sensitive (c(L)=0.1 microM), simple, and rapid. The procedure using horseradish peroxidase and the reaction of TMB oxidation was used to determine ascorbic acid in fruit juices, milk and sour-milk products for babies' nutrition. PMID- 17723516 TI - Encapsulation of biomolecules for bioanalytical purposes: preparation of diclofenac antibody-doped nanometer-sized silica particles by reverse micelle and sol-gel processing. AB - In recent years, the sol-gel technique has attracted increasing interest as a unique approach to immobilize biomolecules for bioanalytical applications as well as biochemical and biophysical studies. For this purpose, crushed biomolecule doped sol-gel glass monoliths have been widely used. In the present work, for the first time, the encapsulation of anti-diclofenac antibodies in silica nanoparticles was carried out by a combination of reverse micelle and sol-gel technique. Cyclohexane was used for the preparation of the microemulsion as organic solvent, while surfactant Igepal CO-520 was found to be the optimal stabilizer. The antibody source was a purified IgG fraction originating from a polyclonal rabbit antiserum. Tetramethyl orthosilicate (TMOS) was used as precursor. Rather uniform, monodispersed and spherical silica particles of about 70nm diameter size were fabricated, as was demonstrated by transmission electron microscopy (TEM) and scanning electron microscopy/energy dispersive X-ray fluorescence analysis (SEM/EDX). The biological activity of the encapsulated antibodies was evaluated by incubation of the nanoparticles with a diclofenac standard solution and analysis of the filtrate and followed washing solutions by a highly sensitive enzyme-linked immunosorbent assay (ELISA), using non-doped particles as blanks. While only about 6% of the added diclofenac was nonspecifically retained by the blank, the corresponding amount of about 66% was much higher with the antibody-doped particles. An obvious advantage of this approach is the general applicability of the developed technique for a mild immobilization of different antibody species. PMID- 17723517 TI - Brownian motion of aggregating nanoparticles studied by photon correlation spectroscopy and measurements of dynamic magnetic properties. AB - We have investigated colloidal stability of magnetic nanoparticle suspensions in different buffer systems and NaCl concentrations commonly used for biological applications. We have also investigated how conjugation of proteins to magnetic nanoparticles affects colloidal stability. Two different techniques, giving complementary information on the state of the particle system studied, have been used and compared. We have monitored the rotational Brownian motion of particles using measurements of dynamic magnetic susceptibility in the frequency domain. The results were processed using an algorithm that enables us to quantify changes of particle size distribution for particle suspensions subjected to various buffer conditions. The measurements were compared to results obtained for the translational Brownian motion of the same nanoparticles using photon correlation spectroscopy (PCS). We demonstrate that the complementarity of the two techniques enables more precise characterization of particles in suspension, particularly for suspensions of particles with a wide distribution in size and shape, or systems that are close to the onset of agglomeration. PMID- 17723518 TI - Rapid detection of toxicity in wastewater: recent developments with manometric respirometry. AB - Manometric respirometry can be used for the direct toxicity assessment (DTA) of wastewater. A first prototype portable system for field use as well as the principle of operation has been reported previously [A. Tzoris, D. Cane, P. Maynard, E.A.H. Hall, Anal. Chim. Acta 460 (2002) 257; A. Tzoris, D. Fearnside, M. Lovell, E.A.H. Hall, Environ. Toxicol. 17 (2002) 284; A. Tzoris, V. Fernandez Perez, E.A.H. Hall, Sens. Actuators B 105 (2005) 39]. In this report we examine the simple mathematical derivation of the principle and identify some design parameters that could be altered or improved. Hence by changing the geometry of the respiration chamber aiming at a larger surface area and smaller air headspace volume combined with sample stirring for improved aeration, the response of the instrument was improved by at least 50%. Data obtained from real samples as well as data from a comparative study with a lab-based respirometer routinely used in toxicity assessment is presented. Correlation was excellent with the advantage that a test could be completed in 6min or with five repeat measurements the data could be collected within a 10min measurement period. Using a 25% inhibition threshold, all samples found toxic by the standard method were also found toxic by the Baroxymeter method and dilution factors could be estimated for pretreatment of the toxic waste prior to release to a processing plant. PMID- 17723519 TI - Combination of immunomagnetic separation with flow cytometry for detection of Listeria monocytogenes. AB - Listeria monocytogenes can grow at the low temperature commonly used in the storage and transportation of food, and the number of cases of food poisoning caused by L. monocytogenes has increased recently in the US and Europe. Several methods of detecting L. monocytogenes cells have been proposed; however, all existing methods require approximately 48 h incubation. In this study, we attempted rapid detection of L. monocytogenes using flow cytometry (FCM). The method is based on measuring the number of L. monocytogenes cells by using a combination of FCM and immunomagnetic separation (IMS). First, polyclonal antibodies (anti-L. monocytogenes rabbit IgG-FITC) conjugated with fluorescein isothiocyanate (FITC) were reacted with L. monocytogenes cells, and then FCM was applied. The cell numbers were determined by FCM using a traditional colony counting method in the range of 10(4)-10(8) cells ml(-1). Tetrameric antibody complexes (TAC) were used because they can recognize both magnetic and FITC molecules on the FITC-conjugated antibodies. FITC-labeled L. monocytogenes cells were reacted with a secondary antibody (TAC) bound to magnetic beads. Then, IMS was used. The method is suitable for detection in the range of 10(2)-10(8)cells ml(-1). The FCM assay enumerated the cells within 1 min and the total assay time, including sample preparation, was less than 2 h. PMID- 17723520 TI - Miniaturized fluorescence detection chip for capillary electrophoresis immunoassay of agricultural herbicide atrazine. AB - This paper reports a miniaturized fluorescence detection chip for capillary electrophoresis immunoassay of atrazine, which effectively reduces the size of fluorescence detection system. The photodiode with fluorescence filter was embedded in PDMS (polydimethylsiloxane) microfluidic chip and was placed just below the microfluidic channel. This detection chip is only few mm thick without loss of fluorescence due to the proximity of photodiode and channel. To investigate the feasibility of in situ detection of agricultural herbicide, atrazine was detected using capillary electrophoresis immunoassay in microfluidic chip. Mixture of 570 nM fluorescence-labeled atrazine (Ag*) and 700 nM anti atrazine antibody (Ab) was injected and separated in 25 mm long microfluidic channel. The separated peaks of Ab-Ag* immunocomplex and Ag* were detected by the miniaturized detector and the change of peak magnitude was also observed with the variation of Ab concentration. The result was verified with those of external PMT (photomultiplier tube) and commercial capillary electrophoresis system. Hence, we have demonstrated the feasibility of portable CE immunoassay of atrazine with on chip fluorescence detector. PMID- 17723521 TI - Analysis of size characterized manganese species from liver extracts using capillary zone electrophoresis coupled to inductively coupled plasma mass spectrometry (CZE-ICP-MS). AB - Mn is of toxicological concern because overexposure can lead to progressive, permanent neurodegenerative damage. Monomethyl-Mn-pentadienyl-tricarbonyl (MMT) is used as an anti-knock agent in fuel. Exhausted Mn compounds are absorbed in the lung and transported to the liver. Extended exposure causes an overflow of the liver with Mn species moving e.g. to the brain, causing irreversible central nervous system (CNS) disorders like Manganism. This paper focuses on experiments for getting more information on Mn species in liver extracts. The investigations are performed with respect to (1) a size characterization and (2) a subsequent identification of the Mn species in liver extracts using preparative size exclusion chromatography (SEC) followed by capillary zone electrophoresis coupled to inductively coupled plasma mass spectrometry (CZE-ICP-MS). First, extracts were analyzed using a mass calibrated SEC column coupled to ICP-MS detection. The chromatogram showed the 55 Mn-trace and proved main Mn elution between ca. 60-150 kDa. Second, liver extracts were fractionated on the same SEC column, however, now the effluent was directed to a fraction collector. This resulted in fractions containing pre-purified, size characterized Mn species per fraction. It turned out that the Mn concentrations per fraction reflected roughly the previous on line Mn trace. Third, the fractions were subject to CZE-ICP-MS, where the MS was operated additionally with dynamic reaction cell (DRC) technique. From size characterization (with SEC coupled on-line to ICP-MS or connected to a fraction collector and subsequent Mn determination in fractions) it was shown that most Mn species from liver extract were of high molecular mass (HMM) nature as they eluted mostly between 50 and 80 min, corresponding to ca. 60-150 kDa. With the two-dimensional speciation approach employing first SEC and then CZE-ICP-DRC-MS together with standard addition method, a series of Mn species was identified. Mn species predominantly were Mn-enzymes e.g. arginase, isocitric dehydrogenase, galactosyltransferase, prolidase, pyruvate carboxylase and oxalate oxidase. A typical Mn-transporter--Mn-albumin-- was also seen, whilst Mn-transferrin obviously was degraded during SEC separation. This Mn-compound (independent whether as a standard or from liver extract) was not stable during SEC even at the finally chosen physiological conditions. PMID- 17723522 TI - An automated extraction approach for isolation of 24 polyaromatic hydrocarbons (PAHs) from various marine matrixes. AB - An efficient and selective analytical method for determination and quantification of 24 various polyaromatic hydrocarbons (PAHs) in blue mussel (Mytilus edulis), salmon fillet (Salmo salar), fish oil and fish feed has been developed. The samples were extracted by means of accelerated solvent extraction (ASE) technique followed by a purification step with gel permeation chromatography (GPC). Identification and quantification were performed by using GC/MS. The novel combination of silica and alumina in the extraction step furnishes highly purified analytes for the most of the 24 PAHs investigated, and thus a fast and selective analytical method is developed. A small limitation with the method concerns the quantification of acenaphthene (Ace), fluorene (Fl), pyrene (Py) and benzo[a]anthracene (BaA), as the found values for these compounds do not match the certified values (SRM 2977, mussel tissue). Chrysene (Chr) and triphenylene (Tph) give unresolved peaks. The limits of detection (LOD) and limits of quantification (LOQ) found for benzo[a]pyrene (BaP) were 1.7 and 0.44 pg/g (LOD), and 5.8 and 1.5 pg/g (LOQ) for salmon fillet and blue mussel, respectively. This is in a very good accordance with respect to the European Community legislation for official control of BaP levels in foodstuff. The method may be used for qualitative identification of petroleum compounds in marine matrixes. PMID- 17723524 TI - Determination of organochlorine pesticides and polychlorinated biphenyls in chicken eggs by matrix solid phase dispersion. AB - A multiresidue method for the determination of 20 organochlorine pesticides (aldrin, endrin, dieldrin, alpha-BHC, beta-BHC, gamma-BHC, delta-BHC, alpha chlordane, gamma-chlordane, 4,4'-DDE, 4,4'-DDT, 4,4'-DDD, endosulfan I, endosulfan II, endosulfan sulfate, endrin aldehyde, heptachlor, heptachlor epoxide, endrin ketone and methoxychlor) and eight PCB congeners (PCB 20, 28, 52, 101, 118, 138, 153, 180) in chicken eggs has been developed and validated. The samples were extracted by a simple and fast matrix solid-phase dispersion (MSPD) method using Florisil as the sorbent material and dichloromethane/hexane (1:1) as the eluting system. Further purification of the extracts was conducted using a conventional clean-up procedure with concentrated sulphuric acid. Determination and quantitation of PCBs and OCs residues was carried out using a gas chromatograph equipped with an electron capture detector (GC-ECD). A mass spectrometric detector (GC-MS) in the selected ion monitoring (SIM) mode was used for confirmation purposes. The method detection limits were <0.7 ng g(-1) for all PCBs and OCs and the relative standard deviations for analyses of samples fortified over the range of 10-200 ng g(-1) were <8%. All compounds provided average recoveries (spiked at five concentration levels) ranging from 82% to 110%. The proposed method was used to analyze 30 commercial products taken from local markets in the course of a 3-month sampling campaign. PMID- 17723523 TI - Continuous determination of volatile products in anaerobic fermenters by on-line capillary gas chromatography. AB - Bio-ethanol and biogas produced during the anaerobic conversion of organic compounds has been a subject of great interest since the oil crisis of the 1970s. In ethanol fermentation and anaerobic treatment of wastewaters, end-product (ethanol) and intermediate-products (short-chain fatty acids, SCFA) cause inhibition that results in reduced process efficiency. Control of these constituents is of utmost importance for bioreactor optimization and process stability. Ethanol and SCFA can be detected with precision by capillary gas chromatography usually conducted in off-line measurements. In this work, an on line monitoring and controlling system was developed and connected to the fermenter via an auto-sampling equipment, which could perform the feeding, filtration and dilution of the sample and final injection into the gas chromatograph through an automation-based programmed procedure. The sample was continuously pumped from the recycle stream of the bioreactor and treated using a microfiltration unit. The concentrate was returned to the reactor while the permeate was quantitatively mixed with an internal standard solution. The system comprised of a gas chromatograph with the flow cell and one-shot sampler and a PC with the appropriate software. The on-line measurement of ethanol and SCFA, directly from the liquid phase of an ethanol fermenter and a high-rate continuous mode anaerobic digester, was accomplished by gas chromatography. Also, this monitoring and controlling system was proved to be effective in the continuous fermentation of alcohol-free beer. PMID- 17723525 TI - Uncertainty associated to the analysis of organochlorine pesticides in water by solid-phase microextraction/gas chromatography-electron capture detection- evaluation using two different approaches. AB - As the performances of analytical instrumentation are being gradually enhanced, the limits of detection become increasingly lower, allowing more environmental contaminants to be determined in different matrices. Problems emerge when dealing with data from different origins, once the uncertainty of the results is difficult to be compared, especially if its calculation procedure is rather different, as very often happens. Samples of two organochlorine pesticides of somewhat opposite characteristics (lindane and heptachlor, classified as persistent organic pollutants--POPs) were analyzed in aqueous media using headspace solid-phase microextraction (SPME) prior to gas chromatography-electron capture detection (GC-ECD) and this methodology was in-house validated. Detection limits of 0.097 and 0.050 microg l(-1), average intermediate precision of 11.6% and 27.5%, and average recovery of 95.6% and 103.0%, for lindane and heptachlor, respectively, were found. In the absence of available interlaboratory studies to assess the reliability of the results, the expanded uncertainty was calculated following two different approaches (bottom-up/Eurachem and modified top-down) and the results were compared. Globally it was clearly shown that, for both pesticides, the lower the concentration range, the higher the uncertainty associated to the results. Expanded uncertainties estimated by bottom-up/Eurachem approach varied from 51% to 14% for a lindane concentration range of 0.1-1 microg l(-1), and from 48% to 24% for a heptachlor range of 0.1-2 microg l(-1). Modified top-down approach pointed to 44% (lindane and heptachlor) in the same ranges, meaning that a uniform procedure for uncertainty estimation should be adopted. PMID- 17723526 TI - Evaluation of solid sorbents for the determination of fenhexamid, metalaxyl-M, pyrimethanil, malathion and myclobutanil residues in air samples: application to monitoring malathion and fenhexamid dissipation in greenhouse air using C-18 or Supelpak-2 for sampling. AB - A methodology is described for greenhouse air analysis by sampling fenhexamid, pyrimethanil, malathion, metalaxyl-M and myclobutanil in solid sorbents. Pesticides were determined by gas chromatography with NP Detector. The trapping efficiency of XAD-2, XAD-4, Supelpak-2, Florisil and C-18 at different sampling conditions (rate, time and air humidity) and pesticides concentration levels has been evaluated. No breakthrough was observed in the range of concentration studied (0.10-75 microg of each pesticide). In almost all the cases good stability results were obtained. Personal pumps have been used with selected sorbents (Supelpak-2 and C-18) in order to sample malathion and fenhexamid in air of experimental greenhouse after their application in a tomato crop. The dissipation process of the analytes in various time periods after application has been studied. Malathion concentrations varied between 20.1 microg m(-3) just after application and 1.06 microg m(-3) 3 days later. Fenhexamid concentrations, determined by high performance liquid chromatography with UV detection, fall rapidly; after 12 h post-application being below 0.50 microg m(-3). PMID- 17723527 TI - Screening method for organophosphorus insecticides and their metabolites in olive oil samples based on headspace solid-phase microextraction coupled with gas chromatography. AB - This work is focused on the effectiveness of headspace solid-phase microextraction (HS-SPME) for the analysis of nine organophosphorus (OPs) insecticides (dimethoate, diazinon, fenitrothion, malathion, fenthion, parathion ethyl, methyl bromophos, methidathion, ethion) and four metabolites (omethoate, malaoxon, fenthion sulfoxide and fenthion sulfone) residues in olive oil samples. The efficiency of six fibre types with different film thickness was compared. PDMS (100 microm) was found to be the most suitable fibre for the analysis of OPs in olive oils. Optimization of SPME conditions (stirring rate, extraction time, temperature, salt addition) was based on previous developed method in the laboratory that was enriched with additional analytes including major metabolites. In addition, the effect of the oil matrix on the pesticide recoveries was evaluated using spiked oil samples of different composition (acidity, fatty acids, triglycerides, sterols). It was found that only acidity and total amount of sterols are the main factors influencing the SPME efficiency. Matrix effects were compensated for, by using the internal standard method for the quantification of pesticides. The recoveries at three spiking levels were between 80% and 106% with R.S.D. (%) values below 10% in most cases. Good linearity (R2>0.985) was observed in the 0.025-0.50 mg kg(-1) concentration range with satisfactory R.S.D. (%) values of 4.5-10.4%. The method allowed detection of the tested compounds at concentrations below 0.010 mg kg(-1) with GC-FTD detection. In addition, intra- and inter-day precision was satisfactory (R.S.D. (%) <10%). The performance results confirm the usefulness of the proposed methodology for the analysis of OPs in olive oils. Moreover, the maximum residue limits required by European and international regulations can be attained without difficulty. Finally, the method was applied to 30 virgin olive oil samples from major olive production areas of Greece in the framework of an extended monitoring survey of OPs residues in olive oil. The most commonly found pesticides were fenthion, dimethoate and ethion in levels that did not exceed the MRLs. PMID- 17723528 TI - Coupling of headspace solid phase microextraction with ultrasonic extraction for the determination of chlorinated pesticides in bird livers using gas chromatography. AB - In the present study a combined analytical method involving ultrasonic extraction (USE), sulfuric acid clean-up and headspace solid-phase microextraction (HS-SPME) was developed for the determination of chlorinated pesticides (CPs) in bird livers. Extraction of CPs from 1g of liver was performed by ultrasonication for 30 min using 20 mL of solvent mixture (n-hexane:acetone (4:1, v/v)). The extract was subsequently subjected to a clean-up step for lipid removal. A comparative study on several clean-up procedures prior to the HS-SPME enrichment step was performed in order to achieve maximum recovery and optimal clean-up efficiency, which would provide suitable limits of detection in the gas chromatographic analysis. For this purpose, destructive (sulfuric acid or sodium hydroxide treatment) and non-destructive (alumina column) clean-up procedures has been assayed. The treatment of the extract with 40% (v/v) H2SO4 prior to HS-SPME process showed the best performance since lower detection limits and higher extraction efficiencies were obtained. The method detection limit ranged from 0.5 to 1.0 ng g(-1) wet weight and peak areas were proportional to analyte concentrations (r2>0.990) in the range of 5-500 ng g(-1) wet wt. The method was found to be reproducible (R.S.D.<10%) and effective under the operational conditions proposed and was applied successfully to the analysis of CPs in liver tissues of various bird species from Greece. PMID- 17723529 TI - Analysis of phenolic acids as chloroformate derivatives using solid phase microextraction-gas chromatography. AB - In the presented study, a simple and original procedure of phenolic acids derivatization treated by ethyl and methyl chloroformate performed in an aqueous media consisting of acetonitrile, water, methanol/ethanol and pyridine has been modified and optimized. Seven phenolic acid standards-caffeic, ferulic, gallic, p coumaric, protocatechuic, syringic and vanillic were derivatized into corresponding methyl/ethyl esters and subsequently determined by the means of gas chromatography connected to the flame-ionisation detector (FID). Some selected validation parameters as linearity, detection and quantitation limits and peak area repeatability were valued. The total time of gas chromatography (GC) analysis was 24 min for methyl chloroformate and 30 min for ethyl chloroformate derivatization. The more suitable methyl chloroformate derivatization was used for further experiments on the possibility of multiple pre-concentration by the direct solid phase microextraction technique (SPME). For this purpose, polyacrylate (PA), polydimethylsiloxane (PDMS), carboxen/polydimethylsiloxane (CAR/PDMS) and polydimethylsiloxane/divinylbenzene (PDMS/DVB) fibres were tested and the extraction conditions concerning time of extraction, temperature and time of desorption were optimized. The most polar PA fibre gave the best results under optimal extraction conditions (50 min extraction time, 25 degrees C extraction temperature and 10 min desorption time). As a result, the total time of SPME-GC analysis was 74 min and an increase in method sensitivity was reached. The limits of quantitation (LOQ) of p-coumaric, ferulic, syringic and vanillic acid esters after SPME pre-concentration were 0.02, 0.17, 0.2 and 0.2 microg mL(-1), respectively, showing approximately 10 times higher sensitivity in comparison with the original GC method. PMID- 17723530 TI - Doping control analysis in human urine by liquid chromatography-electrospray ionization ion trap mass spectrometry for the Olympic Games Athens 2004: determination of corticosteroids and quantification of ephedrines, salbutamol and morphine. AB - A new liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) (n) ion trap method for the determination of corticosteroids in urine has been developed and validated. Some anabolic agents, such as epitrenbolone, trenbolone, 2-hydroxymethylformebolone, tetrahydrogestrinone, gestrinone and formoterol were included in the LC-ESI-MS method. Matrix interference, specificity, identification capability, carry over and robustness were estimated as validation parameters. Recoveries ranged from 74 to 113% at the minimum required performance limit (MRPL), which is 30 ng mL(-1) for corticosteroids and 10 ng mL(-1) for anabolic agents. Methods for the confirmation and quantification of norpseudoephedrine, ephedrine, methylephedrine, salbutamol, morphine and morphine glucuronide were also developed and validated and in order to minimize analysis time, direct urine injection was used. These methods proved to be specific, accurate and precise across a calibration range for each substance since matrix interference, specificity, carry over, within and between run precision, limit of detection, limit of quantification, intermediate precision and uncertainty were estimated. PMID- 17723531 TI - Development of a novel liquid chromatography--evaporative light scattering detection method for bacitracins and applications to quality control of pharmaceuticals. AB - A novel liquid chromatography method for the direct determination of bacitracin main components (Bc-A, -B1, -B2 and -B3), a basic, cyclic polypeptide antibiotic, was developed and validated, based on ion pairs formation with trifluoroacetic acid (TFA) and evaporative light scattering detection (ELSD). The selected analytical column was the Waters Nova-pak C8 (3.9 x 150 mm), for which the optimum (using modified Simplex algorithm) mobile phase was H2O-ACN (73:27, v/v) containing 0.80 microL mL(-1) of TFA, at a flow rate of 1.0 mL min(-1). Optimized ELSD parameters were: nebulizing gas (nitrogen) pressure=3.5 bar, evaporation temperature=50 degrees C, detector gain=12. Retention time of Bc-B1, -B2, -B3, -A and -F (oxidative degradation product of Bc-A) was 5.3, 5.8, 7.7, 8.7, 15.9 min, respectively, while zinc ions and related peptides were eluted at 1.3-1.9 min. A logarithmic calibration curve was obtained for each component (r>0.998), while the concentration range of total bacitracin was 30-235 microg mL(-1). Detection limits for the individual components were in the range 1.0-1.6 microg mL(-1). The proposed method was applied for the direct determination of Bc components and related peptides in raw materials and pharmaceutical formulations (tablets, powder and aerosol) without tedious pretreatment (for tablets, a liquid-liquid extraction of magnesium with oxine was required). In the case of matrix interference, synthetic standards containing the same amounts of excipients or the standard addition technique were used. Recovery from spiked commercial formulations was ranged from 96.7% to 101.5% (in respect of total Bc). PMID- 17723532 TI - Development of a liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS) method for the quantification of bioactive substances present in olive oil mill wastewaters. AB - A novel liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI MS/MS) method was developed and validated for the simultaneous determination of the bioactive substances hydroxytyrosol, tyrosol and 2-(5 ethylidene-2-oxo-tetrahydro-2H-pyran-4-yl)acetic acid in olive oil mill wastewater samples (OMW). The chromatographic separation was performed on a RP-C8 column using a water-acetonitrile gradient program and the detection was achieved by tandem MS in the negative ion mode. Calibration curves were linear for all bioactive compounds over the range of 1-100 ng injected, while the method exhibited good accuracy, intra- and inter-day precision. The limit of detection and the limit of quantification were in the low to mid pg range and the method was simple and rapid. Because the disposal of OMW is an environmental problem and on the other hand OMW are rich in biologically active compounds that could be recovered and exploited in various applications, the developed method was applied to the monitoring of OMW samples and the quantitative determination of the aforementioned substances. In this way, the original content in bioactive compounds could be assigned in the raw matrix, and the enrichment of the samples by various pretreatment methods could be assessed. Also, full-scan ESI MS was applied to OMW samples for the identification of several compounds known to be present in OMW. PMID- 17723533 TI - Optimization and validation of a high performance liquid chromatography method for the simultaneous determination of vitamins A and E in human serum using monolithic column and diode-array detection. AB - In this study a novel, simple and rapid reversed-phase high performance liquid chromatography (HPLC) procedure for simultaneous determination of vitamins A and E (retinol and alpha-tocopherol) in blood serum has been developed and validated using monolithic column and diode-array detection (DAD). The monolithic column Chromolith Performance RP-18e (100 mm x 4.6 mm) was operated at ambient temperature. One hundred percent methanol at flow rate 2.5 ml min(-1) was used as a mobile phase. Detection of both compounds was performed with diode-array detector, retinol was monitored at 325 nm and alpha-tocopherol at 295 nm. The linear dependence between peak area and concentration ranged from 0.25 to 10.00 micromol l(-1) for retinol and 0.5-50.0 micromol l(-1) for alpha-tocopherol. The limit of detection (LOD) for retinol was 0.02 micromol l(-1) and limit of quantification (LOQ) was 0.07 micromol l(-1). The limit of detection (LOD) for alpha-tocopherol was 0.1 micromol l(-1) and limit of quantification (LOQ) was 0.3 micromol l(-1). Retinol was eluted in 0.8 min and alpha-tocopherol in 1.4 min. The simultaneous analysis of vitamin A and E can be achieved in less than 2 min. The implementation of monolithic column Chromolith Performance shortens the time of analysis of both vitamins four times in comparison with using traditional particulate column Pecosphere C18 (150 mm x 4.6 mm), 5 microm. This fact may play an important role for routine clinical analysis of biological samples. PMID- 17723534 TI - Liquid chromatography-tandem mass spectrometry in chiral study of amlodipine biotransformation in rat hepatocytes. AB - A high proportion of drugs are chiral compounds used as racemic mixtures in a clinical practice. Very often only one of two enantiomers exhibits a desired pharmacological effect. Amlodipine, 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl) 3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine, is a chiral calcium channel blocker, currently used as a racemate in clinical practice. Racemic mixture is used even though it is known that R- and S-amlodipine do not have the same biological activity and only S-amlodipine possesses vasodilating properties. In this work a novel reversed phase liquid chromatography (RP-LC) separation method for amlodipine and its metabolites was developed. Based on this separation chiral aspects of amlodipine biotransformation were studied by incubation of amlodipine and its two individual enantiomers with primary culture of rat hepatocytes. Structure of the metabolites was elucidated using a liquid chromatography (LC) separation with ultraviolet (UV) and mass spectrometry (MS) detection. An LC-tandem MS (MS/MS) method was used to establish fragmentation pattern of amlodipine and its metabolites. Eight metabolites presented in the highest amount were identified and semiquantified by employing an LC separation. Basically two types of metabolites were detected, reduced type--dihydropyridine metabolites and oxidized type--pyridine metabolites. Other metabolic modification included changes of functional groups, e.g., methylester hydrolysis or acetylation of amino group. The results exhibited that R-amlodipine was stereoselectively metabolized by the respective biotransformation enzymes in rat liver hepatocytes and it is also demonstrated by greater extent of R-amlodipine conversion into metabolites where the values for R-amlodipine are for the most metabolites higher than those for metabolites of S-amlodipine. PMID- 17723535 TI - Development and validation of a reversed-phase ion-pair liquid chromatography method for the determination of magnesium ascorbyl phosphate and melatonin in cosmetic creams. AB - A reversed-phase ion-pair high-performance liquid chromatographic method was developed and validated for the determination of magnesium ascorbyl phosphate and melatonin in cosmetic creams. The determination was performed on a BDS C 18 analytical column (250 x 4.6 mm i.d., 5 microm particle size); the mobile phase consisted of 0.020 M tetrabutylammonium hydroxide and 0.025 M potassium dihydrogen phosphate (pH 6.8) mixed with acetonitrile in a ratio (77:23, v/v) and pumped at a flow rate 1.00 ml min(-1). The UV detector was operated at 260 nm. The retention times of the magnesium ascorbyl phosphate, melatonin and chlorthalidone that was used as internal standard, were 6.55, 9.18 and 11.07 min, respectively. Calibration graphs are linear (r better than 0.9990, n=6), in concentration range 1.00-10.00 microg ml(-1) for magnesium ascorbyl phosphate and 0.63-6.25 microg ml(-1) for melatonin. The intra- and inter-day R.S.D. values were less than 6.0%, while the relative percentage error E(r) was less than 3.5% (n=5). The quantitation limits were 0.69 and 0.47 microg ml(-1), for magnesium ascorbyl phosphate and melatonin, respectively. The method was applied to the analysis of a cosmetic cream and proved to be suitable for rapid and reliable quality control. PMID- 17723536 TI - Validation and global uncertainty of a liquid chromatographic with diode array detection method for the screening of azoxystrobin, kresoxim-methyl, trifloxystrobin, famoxadone, pyraclostrobin and fenamidone in grapes and wine. AB - Azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, famoxadone and fenamidone are permitted Q(o) Inhibitor (Q(o)I) fungicides applied to vine in some European countries for the treatment of downy and powdery mildews. In this work, a method is validated for the analysis of these fungicides in grapes and wine. This screening method consists in a simple one step liquid-liquid extraction followed by liquid chromatography (LC) fitted with a diode array detector (DAD). Limits of detection for grapes and wine were below 0.2 mg kg(-1) or mg l(-1), precision was not above 13%, and recoveries were, on average, 95+/ 5% for grapes and 104+/-6% for wine. Global uncertainties evaluated in the concentration range from 0.25 to 2.50 mg l(-1) were below 20%. A confirmatory method by gas chromatography (GC) with mass spectrometry (MS) detection was used. PMID- 17723537 TI - Sensitive and simple liquid chromatographic method with ultraviolet detection for the determination of nifedipine in canine plasma. AB - An isocratic high-performance liquid chromatographic method with detection at 240 nm was developed, optimized and validated for the determination of nifedipine in canine plasma. Liquid-liquid extraction was used as the sample preparation technique. Carbamazepine was used as internal standard. A Hypersil BDS RP-C18 column (250 mm x 4.6 mm, 5 microm) was equilibrated with a mobile phase composed of water and methanol, 45:55 (v/v). Its flow rate was 1 ml min(-1). The elution time for nifedipine and carbamazepine was approximately 12 and 8 min, respectively. Calibration curves of nifedipine in plasma were linear in the concentration range of 1-200 ng ml(-1). Limits of detection and quantification in plasma were 0.5 and 1.5 ng ml(-1), respectively. Recovery was greater than 98%. Intra- and inter-day relative standard deviation for nifedipine in plasma was less than 8.5 and 10%, respectively. This method was applied to the determination of nifedipine plasma levels after administration of commercially available soft gelatine capsules to dogs. PMID- 17723538 TI - Modelling flow rate gradient elution in reversed-phase liquid chromatography. AB - The fundamental equation of flow programming elution was tested in several different types of flow-rate gradients (step, linear, multilinear, parabolic and more combined gradients) implemented in the separation of two multicomponent mixtures of solutes. The retention prediction obtained for all solutes under all flow-programmed conditions was excellent. In addition, although flow programming appears quite limited in its ability to provide improved performance in liquid chromatography, there are specific flow-rate profiles which provide significant improvement in the rearrangement of the peaks within a chromatogram. PMID- 17723539 TI - Contribution to the standardization of the chromatographic conditions for the lipophilicity assessment of neutral and basic drugs. AB - The chromatographic conditions aiming to a better simulation of n-octanol-water partitioning using a base deactivated silica (BDS) column as stationary phase were investigated for structurally diverse basic and neutral drugs. Extrapolated retention factors log k(w), determined using different methanol fractions as organic modifier, were considered as lipophilicity indices. The effect of n decylamine and n-octanol as mobile phase additives was examined and the appropriateness of the final retention outcome to reproduce lipophilicity data was evaluated. Moreover, the influence of n-octanol on the linearity of the log k/methanol fraction relationship and on the uniformity of the retention mechanism was investigated. 1:1 correlation between log k(w) values and the logarithm of the distribution coefficient (logD) was established for basic drugs in presence of both n-decylamine and n-octanol as mobile phase additives. However, for neutral drugs n-decylamine proved to be a sufficient and more important factor than n-octanol. PMID- 17723540 TI - Determination of 226Ra in aqueous solutions via sorption on thin films and alpha spectrometry. AB - An improved spectrometric method to determine the 226Ra activity in aqueous solutions is described. The method involves two stages, a preconcentration stage of 226Ra sorption onto a thin manganese layer and a measurement stage using alpha spectrometry. Manganese oxide thin films were prepared and characterized with X ray diffraction (XRD) and X-ray fluorescence (XRF) analyses. The thin films were found to follow the XRD patterns and chemical formula of the K-birnessite layered exchanger. The preconcentration of radium was studied relative to the initial radium concentration, pH and salt concentrations. The preconcentration kinetics was studied as a function of manganese surface, solution volume and salt concentration. Extensive Monte Carlo calculations were performed to optimise the detection of alpha-particles. In this way, the thin film preparation procedure as well as the radium sorption and the measurement conditions were optimised and detection limits lower than 0.5 mBq L(-1) were obtained for 2d of procedure completion. The method was validated with IAEA standards and it was applied for the determination of 226Ra in bottled waters and also wastewaters from the major thermoelectric plant in Greece. Moreover, the 226Ra distribution coefficients (K(d)) of two differently prepared powder manganese oxides, a crystalline silicotitanate and an aluminium-pillared montmorillonite were determined by gamma spectrometry. 226Ra sorption experiments on silicotitanate thin films were performed and improvements in resolution and reduction of exposure time were observed. PMID- 17723541 TI - Characterization of oil spills in the environment using parallel factor multiway analysis. AB - The aim of this study was to characterize samples of petroleum spills derived from the oily free-phase zone located in the subsurface of a petroleum refinery and to reveal the contained distinct petroleum fractions, thus enabling the identification of the spill origin. The samples were collected from different monitoring wells and were analyzed using gel permeation chromatography (GPC) combined with a UV-diode array detector. The PARAFAC algorithm was employed for the analysis of the 3-D experimental data matrix, which contained the areas under the chromatographic trace, measured for distinct time slices over the 270-440 nm UV range for the whole sample population. The application of the PARAFAC method revealed two significant elution profiles possessing characteristic UV signals, which were attributed to the gasoline and diesel fractions, respectively. A third elution profile was also identified which corresponded to biodegraded heavy fractions. The relative contribution of these compositional features to the oil spill samples was also identified. The presented method can be employed as a rapid and reliable fingerprinting tool in environmental studies, where petroleum pollutants of unknown composition are expected. PMID- 17723542 TI - Surface plasmon resonance imaging as a multidimensional surface characterization instrument--application to biochip genotyping. AB - Surface plasmon resonance imaging (SPRI) sensors allow the characterization of a metal/dielectric interface. Providing proper biochemical functionalization and spatial structuration of the functionalized surface, an optical biochip system- label free and real time--can be achieved. We study the impact of the different physical parameters on the quality of the measurements. Such a SPRI system has a great sensitivity to small variations of the physical parameters (layer optical index, thickness, etc.) occurring at the sensor surface. Precision and reliability of the measurements are provided by a multidimensional approach (4D i.e. spatial coordinates x-y, time t, angle of incidence theta) allowing multiple self-calibration procedures. Such apparatus has already been successfully applied in genomics and proteomics, studying DNA:DNA and oligosaccharide:protein interactions. In this article, we illustrate the advantages of the SPRI setup applied to the detection of gene mutations, using as a model the genetic disease Cystic Fibrosis. The results demonstrate that the system is able to monitor and analyse the interaction under investigation, allowing the diagnosis of genetic single nucleotide polymorphisms by exploiting only a part of the multidimensional potential (x, y, t, theta). PMID- 17723543 TI - Analysis of protein-based binding media found in paintings using laser induced fluorescence spectroscopy. AB - Laser induced fluorescence (LIF) spectroscopy of intrinsic fluorophores from organic media found in paintings (casein, animal glue and egg proteins) provides novel non-invasive means of characterisation of general classes of media on the basis of fluorescence emission arising from the presence of certain amino acids and their degradation byproducts. Proteins from traditionally employed binding media include collagen, casein, albumin and other egg proteins, of animal sources (skins, milk and egg respectively). Wavelength dependence of the spectra is presented for analyses of thin films of protein-based binding media. PMID- 17723544 TI - A study of ancient pottery by means of X-ray fluorescence spectroscopy, multivariate statistics and mineralogical analysis. AB - Energy-dispersive X-ray fluorescence spectroscopy was used to determine the composition of 64 potsherds from the Hellenistic settlement of Orraon, in northwestern Greece. Data classification by principal components analysis revealed four distinct groups of pottery, pointing to different local production practices rather than different provenance. The interpretation of statistical grouping was corroborated by a complementary X-ray diffraction analysis. Compositional and mineralogical data, combined with archaeological and materials' science criteria, allowed addressing various aspects of pottery making, such as selection of raw clays, tempers and firing conditions. PMID- 17723545 TI - Determination of the pesticide carbaryl and its photodegradation kinetics in natural waters by flow injection-direct chemiluminescence detection. AB - A novel flow injection-chemiluminescence method for the quantitative assay of the pesticide carbaryl in environmental samples is presented. The determination is based on the CL-emission generated by the oxidation of the pesticide with potassium permanganate. The linear response of CL-emission versus concentration is valid in the range from 0.01 to 1.0 microg mL(-1), yielding detection limits (S/N=3) as low as 14.8 ng mL(-1). The method shows high reproducibility (R.S.D.=2.29%, n=10) and is subject to minor interferences from various organic and inorganic species likely to be found in natural waters. The suggested method is rapid and capable to be fully automated, thus resulting to a method of satisfactory sampling throughput, with low detection limits and efficient precision for routine analysis. The use of this technique to a new application of direct chemiluminescence involving the determination of carbaryl photodegradation in natural waters was successfully accomplished. PMID- 17723546 TI - Kinetic separation in flow injection spectrophotometry: simultaneous determination of copper and zinc in a single run. AB - A flow injection spectrophotometric method for the simultaneous determination of copper (II) and zinc (II) in mixtures was developed, utilizing metal-zincon complex formation and kinetic differences in the ligand substitution reaction of these complexes with aminopolycarboxylic acids at pH 9.18. The linear range for the determination of zinc is 0.2-9.7 microg ml(-1) and for copper is 0.2-3.5 microg ml(-1). About 90 samples can be determined in 1h. The proposed method has been applied to the determination of zinc and copper in various vitamin formulations with no need for previous separation. PMID- 17723547 TI - Automated sequential injection fluorimetric set-up for multiple release testing of topical formulation. AB - A fully automated sequential injection analysis (SIA) device for simultaneous release testing of multiple ointment samples was devised and applied to the release testing of an ointment containing salicylic acid as an active substance. The SIA system consisted of a bi-directional 5 ml syringe pump, two 8-position selection valves, auxiliary peristaltic pump, fluorescence detector and three Franz cells maintained at 32 degrees C (water bath). The ointment sample was placed on top of a synthetic Millipore GTTP poly(carbonate) membrane (thickness 10 microm, pore size 0.2 microm) of the Franz cell containing 15 ml of aqueous phosphate buffer of pH 7.4 as the acceptor liquid. The samples of the acceptor liquid (50 microl) were aspirated in 15 min intervals for the period of 6 h from each of the 3 cells and dispensed to a fluorescence detector to determine the concentration of salicylic acid (excitation at 297 nm and emission at 405 nm). The volume of the acceptor medium taken for analysis was automatically replenished after each measurement. The calibration curve was rectilinear for 1 100 microg ml(-1) of salicylic acid. The device allowed simultaneous monitoring of the release tests for up to six cells including automated computer-aided evaluation of the release profile parameters. PMID- 17723548 TI - Determination and antioxidant activity evaluation of etodolac, an anti inflammatory drug, by sequential injection analysis. AB - A robust, accurate and sensitive automated procedure for the determination of etodolac, an anti-inflammatory drug, in pharmaceutical formulas by sequential injection analysis, is reported. The same system was also applied to evaluate the antioxidant activity of the drug expressed as Trolox equivalent antioxidant capacity (TEAC). The methodology is based on measuring at 734 nm the decay of absorbance of a solution with the radical 2,2'-azinobis(3-ethylbenzothiazoline-6 sulfonic acid) (ABTS*+) after its reduction by etodolac. Optimum ABTS*+-etodolac reaction was achieved with 0.329 mL of sample and 0.205 mL of ABTS*+ solution. Etodolac was determined at concentrations up to 4.5 x 10(-5) mol L(-1). A solution detection limit of 6.6 x 10(-6) mol L(-1) was obtained under the optimised experimental conditions. A relative standard deviation (n=10) lower than 4.7% with a sample throughput of more than 21 samples/h was obtained. No interference from excipients was observed. The developed methodology was applied in the analysis of pharmaceutical preparations and the obtained results were in good agreement with those furnished by the reference procedure with relative deviations lower than 1.4%. PMID- 17723549 TI - Using on-line solid phase extraction for determination of amiloride in human urine by sequential injection technique. AB - This presented paper deals with a new methodology for the direct determination of amiloride in human urine. The methodology described is based on the sequential injection analysis technique (SIA) coupled with solid phase extraction (SPE) microcolumn. SPE microcolumn was used for selective retention of amiloride, while the urine matrix components were eluted with water carrier flow to the waste. Due to the acid-basic and polarity properties of amiloride molecule and principles of ion-exchange chromatography, it was possible to retain amiloride on the ion exchange sorbent (SPE BAKER WCX-carboxy group). Eluting solution was 0.01 M HNO3+0.1 M KCl, flow rate 20 microl s(-1). The fluorescence detection of amiloride was performed at lambda(em) 385 nm (secondary filter). Recovery was found in the range 96.8-99.4% for 10 times diluted urine, linearity of determination in the range 0.5-100 microg ml(-1) (r=0.998), and 3sigma limit of detection (LOD) was 0.05 microg ml(-1). The whole procedure comprising raw sample pre-treatment, analyte detection and column reconditioning took 8 min. The proposed SIA-SPE method has been applied for direct determination of amiloride in human urine. PMID- 17723551 TI - A smart multisyringe flow injection system for analysis of sample batches with high variability in sulfide concentration. AB - A fully automated smart multisyringe flow injection analysis (MSFIA) system for the monitoring of sulfide in a wide concentration range is proposed. It allows the determination of sulfide in samples containing suspended solids without requiring any preliminary batch sample treatment. The smart system is able to choose by itself the best approach to quantify the analyte, selecting either a spectrophotometric or a reflectometric detection. The method, carried out in a multi-commuted system, is based on the analyte release as hydrogen sulfide from the donor channel of the gas-diffusion module into an alkaline acceptor channel solution, which is merged with N,N-dimethyl-p-phenylenediamine (DMPD) and Fe(III). The in-line generated methylene blue (MB) dye can be delivered to an optical fiber diffuse reflectance sensor or to a flow-cell spectrophotometer according to the analyte concentration. The detection limit (3s(b)/S) was 4.6 microg l(-1). Two linear calibration graphs between 50-1000 and 500-10000 microg l(-1) sulfide for reflectometry and spectrophotometry, respectively, were obtained. The potentialities of this method were assessed via the determination of sulfide at a wide range of concentrations (4.6 microg l(-1) to 100 mg l(-1)). The high selectivity and sensitivity, the low reagent consumption and the miniaturization of the proposed automated method should be highlighted. PMID- 17723550 TI - Modified tubular electrode in a multi-commutated flow system: determination of acetaminophen in blood serum and pharmaceutical formulations. AB - This work describes the construction of a Nafion coated glassy carbon tubular electrode and its use, coupled to a multi-commutated flow system, for the voltammetric determination of acetaminophen in serum and pharmaceutical formulations. The modification of the electrode enhanced the analytical signal intensity and, simultaneously, prevented the electrode surface fouling. The multi commutated system conferred high versatility to the manifold, allowing it to be easily adjusted to each determination without the need to introduce any physical reconfiguration. The on line enzymatic hydrolysis of acetaminophen, giving rise to 4-aminophenol, allowed the problem of interferences resulting from the oxidation of the matrix serum constituents to be overcome. The method presented a linear range up to 5.0 x 10(-4) mol l(-1) with a detection limit of 1.7 x 10(-5) mol l(-1), a sampling rate of 24 determinations per hour and a repeatability (expressed in relative standard deviation) always lower than 3%. The method was applied to serum samples and pharmaceutical formulations and no statistically significant difference between the results obtained by the proposed method and by the reference methods was found, for a confidence level of 95%. PMID- 17723552 TI - Determination of mercury by multisyringe flow injection system with cold-vapor atomic absorption spectrometry. AB - A new software-controlled time-based multisyringe flow injection system for mercury determination by cold-vapor atomic absorption spectrometry is proposed. Precise known volumes of sample, reducing agent (1.1% SnCl2 in 3% HCl) and carrier (3% HCl) are dispensed into a gas-liquid separation cell with a multisyringe burette coupled with one three-way solenoid valve. An argon flow delivers the reduced mercury to the spectrometer. The optimization of the system was carried out testing reaction coils and gas-liquid separators of different design as well as changing parameters, such as sample and reagents volumes, reagent concentrations and carrier gas flow rate, among others. The analytical curves were obtained within the range 50-5000 ng L(-1). The detection limit (3sigma(b)/S) achieved is 5 ng L(-1). The relative standard deviation (R.S.D.) was 1.4%, evaluated from 16 successive injections of 250 ng L(-1) Hg standard solution. The injection and sample throughput per hour were 44 and 11, respectively. This technique was validated by means of solid and water reference materials with good agreement with the certified values and was successfully applied to fish samples. PMID- 17723553 TI - Optical fiber reflectance sensor coupled to a multisyringe flow injection system for preconcentration and determination of 1-naphthylamine in water samples. AB - A novel optical fiber reflectance sensor is coupled to a multisyringe flow injection system (MSFIA) for the preconcentration and determination of 1 naphthylamine (NPA) in water samples using C18 disks (octadecyl groups). NPA, being a first-class carcinogen, is important from a toxicological point of view and, therefore, its quantification is of considerable interest. In this study, the Griess reaction is used for sensitive and selective spectrophotometric determination of NPA. The reaction involves conversion of nitrite into nitrous acid in acidic medium followed by diazotization of sulphanilic acid and formation of a diazonium salt. The diazonium salt is then combined with NPA to form 4 (sulphophenylazo)-1-naphthylamine, an azo dye. This compound is subsequently retained onto a C18 disk followed by spectrophotometric detection at 540 nm, and it is then eluted with methanol in water (80%, v/v), so that the C18 disk is regenerated for subsequent experiments. Under the established optimum conditions, a calibration graph for NPA was constructed. Good linearity was observed within a concentration range from 10 to 160 microg l(-1). The lineal regression equation is A=(0.0027+/-0.0001) [NPA]+(0.0296+/-0.0047), r=0.9991; relative standard deviation values obtained from the analysis of 10 samples of 10, 80 and 160 microg l(-1) are 4.7, 1.2 and 0.6%, respectively. The mean value relative errors for concentrations of 10, 80, 160 microg l(-1) are 3.4, 0.9 and 0.4%, respectively. The detection and quantification limits were 1.1 and 3.7 microg l( 1). A sampling throughput of 14 injections per hour is achieved. The repeatability calculated for five different C18 disks was E(rel)=2.8%. The proposed technique has been validated by replicate analysis (n=6) of several water samples with spiked NPA, giving satisfactory results. PMID- 17723554 TI - Determination of arsenic(III) by flow injection solid phase extraction coupled with on-line hydride generation atomic absorption spectrometry using a PTFE turnings-packed micro-column. AB - A novel flow injection (FI) solid phase extraction method for the determination of arsenic(III) at trace levels was developed, using on-line hydride generation atomic absorption spectrometry (HG-AAS). Selective determination of As(III) was achieved by on-line formation and retention of the pyrrolidine dithiocarbamate arsenic complex As(III)-PDC on the PTFE turnings which are packed in the preconcentration micro-column. The retained complex was eluted by 2 ml 2 mol l( 1) HCl and subsequently introduced on-line into the integrated reaction chamber/gas-liquid separator (RC-GLS). A 1.5% (m/v) NaBH4 solution was used for arsine generation, while a gas stream of N2 was employed for flash release and transportation towards the atomic absorption flow through cell (AAC) for atomization and measurement. The excellent performance of PTFE turnings as sorbent material and the compact design of the RC-GLS result to high sensitivity, selectivity and sampling frequency. For 60s preconcentration time and sample consumption 10.4 ml a sampling frequency of 25 h(-1) and a detection limit of c(L)=0.02 microg l(-1) were obtained. The repeatability, expressed as relative standard deviation (R.S.D.), at 1.0 microg l(-1) As(III), was s(r)=2.8%. The proposed method was successfully applied to the selective determination of As(III) in natural waters and total arsenic determination in certified reference material. PMID- 17723555 TI - Flow injection potentiometric determination of total antioxidant activity of plant extracts. AB - A new flow injection potentiometric (FIP) method, rapid, reproducible and simple to apply, has been developed for the in vitro evaluation of antioxidative capacity of aqueous plant extracts. This method is based on the transient negative signal measurements with a flow-type platinum electrode detector due to the composition change of a [Fe(CN)6]3-/[Fe(CN)6]4- redox-reagent solution. The variables affecting the signal height such as composition and concentration of redox-reagent, injected sample volume, flow rates of carrier and redox-reagent solution streams were studied in details and the conditions were optimized. For the compounds under study, a linear relationship was stated between the potentiometric signal height and the logarithm of antioxidant concentration. It was stated that a wide antioxidant activity range from 1 microM to 10 mM could be determined by the changing concentrations of the hexacyanoferrate(III) from 5 to 0.01 x 10(-4). The present FIP method was applied to quantify relative antioxidant activity (RAA index) of the representative water-soluble antioxidants (ascorbic acid, pyrocatechol, pyrogallol, caffeic acid, chlorogenic acid, gallic acid, tannic acid, uric acid, L-cysteine, trolox). The high sampling rate (100 h( 1)) and a satisfactory reproducibility (R.S.D.=0.7-1.8%, n=5, 0.1 mM each compound) were obtained. The method was also applied to estimate total antioxidant activity (TAA) of real samples (green and black tea infusions, herbal infusions and fresh fruit extracts) and the results were compared with those achieved using well-known in vitro testing methods. PMID- 17723556 TI - Dynamic mass spectrometer for studies of organic and inorganic molecules. AB - Experimental technique is described and relative cross-sections of direct and dissociative ionization of CO2, C4H9OH, C2H5OH, CH3OH, C6H12O6 and C7H8 molecules by electron impact in the near-threshold energy range are obtained. The experiment is performed on a setup with ion mass separation based on a monopole mass spectrometer which is proved to be successful for such a sort of experiments. For the incident electron energy range from 7 to 35 eV the energy dependences of cross-section of appearance of the main molecule ions and the fragment ions formed due to its dissociation are given. PMID- 17723557 TI - Determination of trace elements in serum by dynamic reaction cell inductively coupled plasma mass spectrometry: developing of a method with a desolvating system nebulizer. AB - An inductively coupled plasma mass spectrometer (ICP-MS), equipped with a dynamic reaction cell (DRC) and coupled with a desolvating nebulizing system (Apex-ACM) to reduce the oxide formation, was used in the determination of Al, Co, Cr, Mn, Ni and Se in serum samples. The effect of the operating conditions of the DRC system was studied to get the best signal-to-background (S/B) ratio. The potentially interfering molecular ions at the masses m/z27Al, 59Co, 52Cr, 55Mn, 60Ni and 78Se, were significantly reduced in intensity by using NH3 and H2, as the reaction cell gases in the DRC, while a proper Dynamic Bandpass Tuning parameter q (RPq) value was optimized. The detection limits for 27Al, 59Co, 52Cr, 55Mn, 60Ni and 78Se, estimated with 3-sigma method, resulted to be 0.14, 0.003, 0.002, 0.01, 0.01 and 1.8 microg L(-1), respectively. This analytical method was developed on both a human serum certified reference material and a lyophilized animal serum produced and proposed in an intercomparison study. The results obtained for the reference samples agreed satisfactorily with the certified values. Precision (expressed as CV%) between sample replicates was better than 10% for elements determination, with the only exception of aluminium (14%). PMID- 17723558 TI - On-line monitoring of pine needles combustion emissions in the presence of fire retardant using a "thermogravimetry (TG)-bridge/mass spectrometry method". AB - In this work a new method called TG-bridge/mass spectrometry is presented, for the on-line monitoring of the pine needles combustion emissions in a common lab furnace. The TG-bridge (thermogravimetry-bridge) system has been developed in house as a TG-MS (thermogravimetry-mass spectrometry) interface, for TG-MS analysis. In this work, TG-bridge was used for directly sampling of the combustion emissions from the inside of the furnace and transferring them into the mass spectrometer (MS), without disturbing the sub-pressure conditions inside the MS ion source. The effect of Fire-Trol 931 (a long-term fire retardant) on the emissions, produced during the combustion of pine needles, is tested in the lab for future application in the field. It was shown that in treated samples, increased evolution of ammonia and aromatic compounds took place, compared to untreated samples. Maximum concentrations of specific compounds, such as benzene and toluene, evolved during the combustion experiments in the furnace, were determined. PMID- 17723559 TI - Instrumental analysis of bacterial cells using vibrational and emission Mossbauer spectroscopic techniques. AB - In biosciences and biotechnology, the expanding application of physicochemical approaches using modern instrumental techniques is an efficient strategy to obtain valuable and often unique information at the molecular level. In this work, we applied a combination of vibrational (Fourier transform infrared (FTIR), FT-Raman) spectroscopic techniques, useful in overall structural and compositional analysis of bacterial cells of the rhizobacterium Azospirillum brasilense, with 57Co emission Mossbauer spectroscopy (EMS) used for sensitive monitoring of metal binding and further transformations in live bacterial cells. The information obtained, together with ICP-MS analyses for metals taken up by the bacteria, is useful in analysing the impact of the environmental conditions (heavy metal stress) on the bacterial metabolism and some differences in the heavy metal stress-induced behaviour of non-endophytic (Sp7) and facultatively endophytic (Sp245) strains. The results show that, while both strains Sp7 and Sp245 take up noticeable and comparable amounts of heavy metals from the medium (0.12 and 0.13 mg Co, 0.48 and 0.44 mg Cu or 4.2 and 2.1 mg Zn per gram of dry biomass, respectively, at a metal concentration of 0.2 mM in the medium), their metabolic responses differ essentially. Whereas for strain Sp7 the FTIR measurements showed significant accumulation of polyhydroxyalkanoates as storage materials involved in stress endurance, strain Sp245 did not show any major changes in cellular composition. Nevertheless, EMS measurements showed rapid binding of cobalt(II) by live bacterial cells (chemically similar to metal binding by dead bacteria) and its further transformation in the live cells within an hour. PMID- 17723560 TI - Oxidative stability and radical scavenging activity of extra virgin olive oils: an electron paramagnetic resonance spectroscopy study. AB - The oxidative stability of extra virgin olive oils (EVOO) from the Greek island of Crete was evaluated by electron paramagnetic resonance (EPR) spectroscopy and the spin trapping technique. The spin trap N-t-butyl-alpha-phenylnitrone (PBN) was added to the olive oil samples and the production of free radicals was monitored during heating at 70 degrees C. Induction time for the accelerated oxidation of virgin olive oils at 70 degrees C was determined. The EPR results were compared with the oxidative stability values provided by the Rancimat method at 110 degrees C and high linear correlations were found (r=0.922). EPR spin trapping provides a sensitive and rapid method for evaluating the oxidative stability of EVOO. The same samples of Greek extra virgin olive oils were also examined for their radical scavenging activity (RSA) toward the stable galvinoxyl radical by EPR spectroscopy. The decrease of the intensity of the EPR signal upon incubation time was followed. Both oxidative stability and radical scavenging activity of EVOO samples were correlated to their content in polyphenols and tocopherols. PMID- 17723561 TI - Applications of Fourier transform-infrared spectroscopy to edible oils. AB - Recent developments in Fourier transform infrared (FT-IR) spectroscopy instrumentation extend the application of this technique to the field of food research, facilitating particularly the studies on edible oils and fats. In this work, FT-IR spectroscopy is used as an effective analytical tool in order: (a) to determine extra virgin olive oil adulteration with lower priced vegetable oils (sunflower oil, soyabean oil, sesame oil, corn oil) and (b) to monitor the oxidation process of corn oil samples undergone during heating or/and exposure to ultraviolet radiation. A band shift observed at 3009 cm(-1) assigned to the C_H stretching vibration of the cis-double bond, allows the determination of extra virgin olive oil adulteration. Changes in the 3050-2800 and 1745 cm(-1) spectral region appear after heating at elevated temperatures and aid the oxidation process monitoring. In addition, an analytical technique for the measurement of carbonylic compounds in oils, produced after heating, is applied. The possible antioxidant effect of oregano is also discussed. PMID- 17723562 TI - New simple spectrophotometric assay of total carotenes in margarines. AB - Direct and reliable spectrophotometric method for assaying total carotenes (TC) in margarines with the minimum of sample manipulation is proposed. For the first time saponification step used in determination of carotenes in margarines was omitted leading to a substantial cost saving and reduction of time needed to complete the analysis. The resulting analytical procedure is characterized in details in terms of the figures of merit. The method is sensitive, precise and accurate; for both, standard additions and calibration in soybean oil, recovery ranges between 98 and 102%. For the most accurate analyses the approach of standard additions is preferred but for quick routine analyses this latter can be replaced by the calibration in soybean oil. Limit of detection value (LOD=3S.D.(B)/a, where S.D.(B) is the standard deviation of the blank, "a" is the slope of calibration line) as low as 12 microg TC/100 g was achieved in soybean oil enabling the sensitive detection. Concentration of TC in margarines declared as being coloured with beta-carotene (carotene) ranges between 0.3 and 0.9 mg/100 g while in carrot extract-coloured margarine TC is 0.2 mg/100 g. PMID- 17723563 TI - Complexation efficiency of differently fixed 8-hydroxyquinoline and salicylic acid ligand groups for labile aluminium species determination in soils- comparison of two methods. AB - Two methods utilizing the complexation of labile Al species by 8-hydroxyquinoline (HQN) and salicylic acid (SA) ligand groups were developed for aluminium operationally defined fractionation in acid soils. First, the solid phase extraction (SPE) procedure by a short-term ion-exchange batch reaction with chelating resins Iontosorb Oxin and Iontosorb Salicyl containing both ligand groups was used previously. Second, the 8-hydroxyquinoline, salicylic acid and ammonium salicylate agents with different concentrations by a single extraction protocol were applied in this paper. The flame atomic absorption spectrometry (FAAS) and optical emission spectrometry with inductively coupled plasma were used for aluminium quantification. The comparison of results from both methods show the possibility to supersede the first laborious method for the second simpler one in Al environmental risk assessment. The use of 1% 8-hydroxyquinoline in 2% acetic acid and 0.2% salicylic acid by a single extraction protocol without a need of sample filtration can supersede the SPE procedure in the Al pollution soil monitoring. Finally, the new scheme usable in a laboratory and moreover, directly in a field was proposed for Al fractionation in solid and liquid environmental samples. The labile Al species in soils and sediments are separated after their single leaching by 8-hydroxyquinoline or salicylic acid without a need of sample filtration. The labile Al species in soil solutions and natural waters are separated after their ultrafiltration followed by the SPE procedure with Iontosorb Oxin or Iontosorb Salicyl. PMID- 17723564 TI - Local factor analysis of rank-deficient reaction systems. AB - The analysis of spectral measurement data sets using local factor analysis (LFA) requires the rank of the sub-matrix under study to be equal to the number of absorbing species present in the associated sub-system. However, because of mass balance or kinetic constraints, LFA will fail if local rank deficiency occurs. A local rank deficiency sub-system may be present in a global full-rank reaction system or a rank-deficient one. In this paper, the problems occurring when using window target-testing factor analysis (WTTFA), one type of the LFA methods, in a local rank-deficient situation are shown. A new augmented WTTFA (AWTTFA) is then proposed for the correct use of WTTFA when rank deficiency occurs. Principles of this new method have been demonstrated by a simulated kinetic system and an industrial batch data set. PMID- 17723565 TI - Antimicrobial peptide-based array for Escherichia coli and Salmonella screening. AB - Numerous bacteria, plants, and higher organisms produce antimicrobial peptides (AMPs) as part of their innate immune system, providing a chemical defense mechanism against microbial invasion. Many AMPs exert their antimicrobial activity by binding to components of the microbe's surface and disrupting the membrane. The goal of this study was to incorporate AMPs into screening assays for detection of pathogenic species. Surface-immobilized AMPs such as polymyxins B and E could be used to detect Salmonella typhimurium and Escherichia coli O157:H7 in two assay formats: direct and sandwich. Both types of assay confirmed that the peptides were immobilized in active form and could bind cells in a concentration-dependent manner. Cell binding to the AMPs was peptide-density dependent. This method for monitoring pathogen binding was extended to include other cationic AMPs such as cecropin A, magainin I and parasin. Detection limits (LODs) for E. coli O157:H7 and S. typhimurium obtained with AMPs during sandwich assays were in the ranges of 5x10(4) to 5x10(5) and 1x10(5) to 5x10(6)cells mL( 1), respectively. The different AMPs showed significantly different affinities for the two bacterial species; the potential for classification of pathogens based on different binding patterns to AMPs is discussed. PMID- 17723566 TI - Gold nanoelectrode ensembles for direct trace electroanalysis of iodide. AB - A procedure for the standardization of ensembles of gold nanodisk electrodes (NEE) of 30 nm diameter is presented, which is based on the analytical comparison between experimental cyclic voltammograms (CV) obtained at the NEEs in diluted solutions of redox probes and CV patterns obtained by digital simulation. Possible origins of defects sometimes found in NEEs are discussed. Selected NEEs are then employed for the study of the electrochemical oxidation of iodide in acidic solutions. CV patterns display typical quasi-reversible behavior which involves associated chemical reactions between adsorbed and solution species. The main CV characteristics at the NEE compare with those observed at millimeter sized gold disk electrodes (Au-macro), apart a slight shift in E1/2 values and slightly higher peak to peak separation at the NEE. The detection limit (DL) at NEEs is 0.3 microM, which is more than one order of magnitude lower than DL at the Au-macro (4 microM). The mechanism of the electrochemical oxidation of iodide at NEEs is discussed. Finally, NEEs are applied to the direct determination of iodide at micromolar concentration levels in real samples, namely in some ophthalmic drugs and iodized table salt. PMID- 17723567 TI - Selective electrochemical sensor for copper (II) ion based on chelating ionophores. AB - Plasticized membranes using 3-(2-pyridinyl)-2H-pyrido[1,2,-a]-1,3,5-triazine 2,4(3H)-dithione (L1) and acetoacetanilide (L2) have been prepared and explored as Cu2+-selective sensors. Effect of various plasticizers, viz. chloronaphthalene (CN), benzyl acetate (BA), o-nitrophenyloctyl ether (o-NPOE), and anion excluders, sodium tetraphenylborate (NaTPB) and oleic acid (OA) was studied in detail and improved performance was observed at several instances. Optimum performance was observed with dithione derivative (L1) having a membrane composition of L1 (5):PVC (120):o-NPOE (240):OA (10). The sensor works satisfactorily in the concentration range 5.0 x 10(-8) to 1.0 x 10(-2) M (detection limit 4.0 x 10(-8) M) with a Nernstian slope of 29.5 mV decade(-1) of activity. Wide pH range (3.0-9.5), fast response time (12s), non-aqueous tolerance (up to 20%) and adequate shelf life (4 months) indicate the vital utility of the proposed sensor. The potentiometric selectivity coefficient values as determined by match potential method (MPM) indicate good response for Cu2+ in presence of interfering ions. The proposed electrode comparatively shows good selectivity with respect to alkali, alkaline earth, transition and some rare earth metals ions. The electrode was used for the determination of copper in different milk powder, water samples and as indicator electrode in potentiometric titration of copper ion with EDTA. PMID- 17723568 TI - Fabrication of a new polyaniline grafted multi-wall carbon nanotube modified electrode and its application for electrochemical detection of hydrogen peroxide. AB - A modified electrode is fabricated by grafting polyaniline (PANI) chains onto multiwalled carbon nanotube (MWNT) for the detection of hydrogen peroxide (H2O2). PANI grafted MWNT modified electrode (PANI-g-MWNT-ME) displays excellent electrocatalytic response to the detection of H2O2 in a concentration range of (1.0-20) x 10(-8) M showing linear response to current, with an extended lower detection limit down to 1 nM. This modified electrode exhibits an accelerated electron transfer at the interface with minimized surface fouling and surface renewability. Further, electrochemical analysis of H2O2 performed in the presence of common interferents such as uric acid, ascorbic acid and acetaminophen with the modified electrode reveals that there is no overlapping signal from the interferents. The combined presence of MWNT and PANI in the modified electrode provides high sensitivity and selectivity. PMID- 17723569 TI - Enhancement of a conducting polymer-based biosensor using carbon nanotube-doped polyaniline. AB - A biosensor with improved performance was developed through the immobilization of horseradish peroxidase (HRP) onto electropolymerized polyaniline (PANI) films doped with carbon nanotubes (CNTs). The effects of electropolymerization cycle and CNT concentration on the response of the biosensor toward H2O2 were investigated. It was found that the application of CNTs in the biosensor system could increase the amount and stability of the immobilized enzyme, and greatly enhanced the biosensor response. Compared with the biosensor without CNTs, the proposed biosensor exhibited enhanced stability and approximately eight-fold sensitivity. A linear range from 0.2 to 19 microM for the detection of H2O2 was observed for the proposed biosensor, with a detection limit of 68 nM at a signal to-noise ratio of 3 and a response time of less than 5s. PMID- 17723570 TI - Effect of condensation phenomena on potentiometric measurements. AB - Results of potentiometric analysis, namely those of pH measurements, depend on temperature control of the experimental setup, as it is expressed in the analytical law, the Nernst equation, starting from the primary level, where reference values are conventionally assigned to standard solutions, through the whole traceability chain, down to the service laboratory. Fundamental studies of pH standards, based on the measurement of the potential of an electrochemical cell without transference, known as Harned cell, containing a platinum-hydrogen electrode and a silver-silver chloride reference electrode, refer condensation phenomena on the portions of the cell walls which are not immersed in the thermostatic bath, as one of the major sources of error in the assessment of both the silver-silver chloride electrode standard potential and on pH values. In this work such effect, which is bound to happen due to significant temperature differences between the ambient air temperature and the water bath, has been quantified, presenting an original contribution to the improvement of the quality of potentiometric analysis results. This was possible due to the availability of a climatic cabin "WALKIN" with a temperature control of +/-0.01 degrees C, which permitted that temperature gradients were built between the thermostat water bath (controlled to +/-0.005 degrees C) where cells filled to about 2/3 full were immersed up to 90% of their height, and the surrounding environment. PMID- 17723571 TI - Electrogenerated chemiluminescence biosensor based on Ru(bpy)3(2+) and dehydrogenase immobilized in sol-gel/chitosan/poly(sodium 4-styrene sulfonate) composite material. AB - A new electrogenerated chemiluminescence biosensor was fabricated by immobilizing ECL reagent Ru(bpy)3(2+) and alcohol dehydrogenase in sol gel/chitosan/poly(sodium 4-styrene sulfonate) (PSS) organically modified composite material. The component PSS was used to immobilize ECL reagent Ru(bpy)3(2+) by ion-exchange, while the addition of chitosan was to prevent the cracking of conventional sol-gel-derived glasses and provide biocompatible microenvironment for alcohol dehydrogenase. Such biosensor combined enzymatic selectivity with the sensitivity of ECL detection for quantification of enzyme substrate and it was much simpler than previous double-layer design. The detection limit was 9.3 x 10(-6) M for alcohol (S/N=3) with a linear range from 2.79 x 10(-5) to 5.78 x 10(-2) M. With ECL detection, the biosensor exhibited wide linear range, high sensitivity and good stability. PMID- 17723572 TI - Simultaneous determination of psychotropic drugs in human urine by capillary electrophoresis with electrochemiluminescence detection. AB - Amitriptyline, doxepin and chlorpromazine are often used as psychotropic drugs in treatment of the various mental diseases, and are also partly excreted by kidney. This work developed a simple, selective and sensitive method for their simultaneous monitoring in human urine using capillary electrophoresis coupled with electrochemiluminescence (ECL) detection based on end-column ECL reaction of tris-(2,2'-bipyridyl)ruthenium(II) with aliphatic tertiary amino moieties. Acetone was used as an additive to the running buffer to obtain their absolute separation. Under optimized conditions the proposed method displayed a linear range from 5.0 to 800 ng mL(-1) for the three drugs with the correlation coefficients more than 0.995 (n=8). Their limits of detection were 0.8 ng mL(-1) (3.6 fg), 1.0 ng mL(-1) (4.5 fg) and 1.5 ng mL(-1) (6.8 fg) at a signal to noise ratio of 3, respectively. The relative standard deviations for five determinations of 20 ng mL(-1) amitriptyline, doxepin and chlorpromazine were 1.7%, 4.2% and 3.6%, respectively. For practical application an extract step with 90:10 heptane/ethyl acetate (v/v) was performed to eliminate the influence of ionic strength in sample. The recoveries of amitriptyline, doxepin and chlorpromazine at different levels in human urine were between 83% and 93%, which showed that the method was valuable in clinical and biochemical laboratories for monitoring amitriptyline, doxepin and chlorpromazine. PMID- 17723573 TI - A new chemiluminescence probe for singlet oxygen based on tetrathiafulvalene anthracene dyad capable of performing detection in water/alcohol solution. AB - A new tetrathiafulvalene-anthracene dyad 1 with two "tetraethylene glycol" units was synthesized and characterized. Strong chemiluminescence was observed upon reaction of dyad 1 with singlet oxygen (1O2), and this reaction shows fairly good selectivity toward 1O2 over other reactive oxygen species. Due to the introduction of two hydrophilic "tetraethylene glycol" units, the detection of 1O2 with dyad 1 can be performed in alcohol/water solution, which is relatively a mild medium when compared with water/tetrahydrofuran solution required by other tetrathiafulvalene-anthracene dyads. Dyad 1 may have a wider use for detection of 1O2 in biological systems. PMID- 17723574 TI - Spectrofluorimetric study of the interaction of copper(II) and bis heterocyclictriazene reagent in the presence of beta-cyclodextrin. AB - A new reagent, 1,3-bis(2-benzothiazolyl-diazoamino)benzene (BBTAB), was first synthesized and characterized by elemental analysis, 1H NMR and IR spectra. The inclusion complex of BBTAB with beta-cyclodextrin (beta-CD) was formed. BBTAB in the inclusion complex or alone reacts with copper(II) to form chelate complex in a slight basic medium, which results in drastic or slight fluorescence enhancement, respectively. The spectrofluorimetric method of trace amount of copper(II) based on the enhancement of inclusion complex by binding with copper(II) was established. The excitation and emission wavelengths of the BBTAB/beta-CD/Cu system are 389 and 480 nm, respectively. Under optimal conditions, a linear response of BBTAB/beta-CD to copper(II) is obtained in the range of 3.0 x 10(-7) to 1.0 x 10(-5) mol L(-1), and the detection limit is determined to be 1.2 x10(-8) mol L(-1). The method is selective, sensitive and simple, and has been used for the determination of trace copper(II) in water samples with satisfactory results. The possible response mechanism of BBTAB/beta CD or BBTAB to copper(II) and the role of beta-CD in the drastic enhancement of fluorescence of BBTAB/beta-CD/Cu system have been discussed. PMID- 17723575 TI - Atmospheric-pressure ionization studies and field dependence of ion mobilities of isomeric hydrocarbons using a miniature differential mobility spectrometer. AB - The ionization pathways and ion mobility were determined for sets of structural isomeric and stereoisomeric non-polar hydrocarbons (saturated and unsaturated cyclic hydrocarbons and aromatic hydrocarbons) using a novel miniature differential mobility spectrometer with atmospheric-pressure photoionization (APPI) to assess how structural and stereochemical differences influence ion formation and ion mobility. The analytical results obtained using the differential mobility spectrometry (DMS) were compared with the reduced mobility values measured using conventional time-of-flight ion mobility spectrometry (IMS) with the same ionization technique. The majority of differences in DMS ion mobility spectra observed among isomeric cyclic hydrocarbons can be explained by the formation of different product ions. Comparable differences in ion formation were also observed using conventional IMS and by investigations using the coupling of ion mobility spectrometry with mass spectrometry (APPI-IMS-MS) and APPI-MS. Using DMS, isomeric aromatic hydrocarbons can in the majority of cases be distinguished by the different behavior of product ions in the strong asymmetric radio frequency (rf) electric field of the drift channel. The different peak position of product ions depending on the electric field amplitude permits the differentiation between most of the investigated isomeric aromatics with a different constitution; this stands in contrast to conventional IMS in which comparable reduced mobility values were detected for the isomeric aromatic compounds. PMID- 17723576 TI - Simultaneous determination of phenyl- and sulfonyl-urea herbicides in river water at sub-parts-per-billion level by on-line preconcentration and liquid chromatography-tandem mass spectrometry. AB - A method based on on-line preconcentration followed by liquid chromatography electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) was developed for the determination of three sulfonyl-urea (thifensulfuron, metsulfuron, chlorsulfuron) and two phenyl-urea (isoproturon and chlortoluron) herbicides in water at sub-ppb concentration ranges. Preconcentration was accomplished using on line enrichment on a C18 cartridge; the procedure was optimized by an evaluation of the breakthrough volumes for the target analytes. Subsequently, LC-ESI-MS/MS was adopted for analytes separation and detection. In particular, a selective reaction monitoring (SRM) approach, based on the detection of a peculiar fragment for each analyte, was chosen for MS/MS analysis, in order to enhance selectivity. Normalization to the response of a phenyl-urea herbicide (chloroxuron), used as an internal standard, was also adopted to achieve a reproducibility enhancement. The described method was applied to the analysis of the target analytes in river water samples and LOD values ranging between 8 and 30 ppt were obtained. PMID- 17723577 TI - High-performance liquid chromatographic determination of biogenic amines in wines with an experimental design optimization procedure. AB - A novel and sensitive HPLC method for determining biogenic amines in wine samples is described. It involves pre-column labeling of the analytes with 1,2 naphthoquinone-4-sulfonate (NQS) and liquid-liquid extraction of derivatives with chloroform for analyte preconcentration and sample clean-up. A linear gradient elution consisting of a mixture of 2% of acetic acid aqueous solution and methanol is used to separate the amine derivatives in a C18 column. The eluted compounds are detected spectrophotometrically at 270 nm. The optimization of both derivatization and separation conditions is accomplished by means of factorial and central composite designs and multicriteria decision functions. The analytical parameters of the method are established using red wine samples. Detection limits range from 0.006 to 0.315 mg L(-1). The run-to-run repeatabilities of retention times and peak areas are around 0.6 and 5.6%, respectively. Recoveries ranging from 91.9 to 105% prove the accuracy of the method for determining histamine, putrescine, cadaverine, tryptamine, phenylethylamine and serotonin in red wines. The proposed method has been applied to the analysis of commercial wines from different Spanish regions. PMID- 17723578 TI - Formation of halogenated by-products of parabens in chlorinated water. AB - Chemical transformations of four alkyl esters of p-hydroxybenzoic acid, parabens, in chlorinated water samples are investigated. Quantification of the parent species and identification of their reaction by-products were performed using gas chromatography in combination with mass spectrometry. Experiments were accomplished considering free chlorine and paraben concentrations at the mg L(-1) and microg L(-1) level, respectively. Concentration of water samples, using solid phase extraction, and silylation of the target species were carried out in order to improve the detectability of parent species and their possible transformation products, achieving quantification limits at the low ng L(-1) level. Under employed experimental conditions, the decrease in the concentrations of parabens followed pseudo-first-order kinetics. Half-lives values obtained for model ultrapure water solutions were in good agreement with those observed in tap water samples. For the first type of sample, only two by-products were detected for each paraben. They corresponded to chlorination of the aromatic ring in one or two carbons situated in ortho-positions to the hydroxyl group. Both species were also generated after the addition of parabens to chlorinated tap water. Moreover, three new transformation products were noticed for each parent compound. They were identified as bromo- and bromochloro-parabens, formed due to the existence of traces of bromide in tap water sources. Experiments carried out by mixing paraben-containing personal care products with tap water, containing free chlorine, confirmed the formation of all above described halogenated by-products. In addition, the presence of the di-chlorinated forms of methyl and propyl paraben has been detected for first time in raw sewage water samples. PMID- 17723580 TI - Development of microwave-assisted extraction followed by headspace solid-phase microextraction and gas chromatography-mass spectrometry for quantification of camphor and borneol in Flos Chrysanthemi Indici. AB - In the work, microwave-assisted extraction (MAE) followed by headspace solid phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS) was developed for quantitative analysis of the bioactive components of camphor and borneol in a traditional Chinese medicines (TCM) of Flos Chrysanthemi Indici. After systematical investigation, the optimal experimental parameters microwave power (400 W), irradiation time (4min), fiber coating (PDMS/DVB fiber), extraction temperature (40 degrees C), extraction time (20 min), stirring rate (1100 rpm), and salt effect (no salt added) were investigated. The optimized method provided satisfactory precision (RSD values less than 12%), good recovery (from 86% to 94%), and good linearity (R2>0.999). The proposed method was applied to quantitative analysis of camphor and borneol in Flos Chrysanthemi Indici samples from 11 different growing areas. To demonstrate the method feasibility, steam distillation was also used to analyze camphor and borneol in Flos Chrysanthemi Indici samples from these different growing areas. The very close results were obtained by the two methods. It has been shown that the proposed ME HS-SPME-GC-MS is a simple, rapid, solvent-free and reliable method for quantitative analysis of camphor and borneol in TCM, and a potential tool for quality assessment of Flos Chrysanthemi Indici. PMID- 17723581 TI - Evaluation of polychlorotrifluoroethylene as sorbent material for on-line solid phase extraction systems: determination of copper and lead by flame atomic absorption spectrometry in water samples. AB - Polychlorotrifluoroethylene (PCTFE) in the form of beads was applied, as packing material for flow injection on-line column preconcentration and separation systems coupled with flame atomic absorption spectrometry (FAAS). Its performance characteristics were evaluated for trace copper determination in environmental samples. The on-line formed complex of metal with diethyldithiophosphate (DDPA) was sorbed on the PCTFE surface. Isobutyl methyl ketone (IBMK) at a flow rate of 2.8 mL min(-1) was used to elute the analyte complex directly into the nebulizer burner system of spectrophotometer. The proposed sorbent material reveal, excellent chemical and mechanical resistance, fast adsorption kinetics permitting the use of high sample flow rates up to 15 mL min(-1) without loss of retention efficiency. For copper determination, with 90 s preconcentration time the sample frequency was 30 h(-1), the enhancement factor was 250, which could be further improved by increasing the loading (preconcentration) time. The detection limit (3s) was c(L)=0.07 microg L(-1), and the precision (R.S.D.) was 1.8%, at the 2.0 microg L(-1) Cu(II) level. For lead determination, the detection limit was c(L)=2.7 microg L(-1), and the precision (R.S.D.) 2.2%, at the 40.0 microg L(-1) Pb(II) level. The accuracy of the developed method was evaluated by analyzing certified reference materials and by recovery measurements on spiked natural water samples. PMID- 17723579 TI - Microwave-assisted UV-digestion procedure for the accurate determination of Pd in natural waters. AB - A procedure was developed for the selective determination of Pd in environmental aquatic solutions. The method is based on a preliminary microwave-assisted UV digestion for the degradation of dissolved organic material, and the subsequent determination of Pd using a recently presented enrichment procedure with ETAAS detection. Due to the simultaneous use of microwave and UV irradiation only extremely small quantities of hydrogen peroxide were necessary to yield a quantitative degradation of interfering organic ligands. Thus the on-line pre concentration of Pd in the digested samples using the complexing agent N,N diethyl-N'-benzoylthiourea was possible without any further sample pre-treatment. Using a sample volume of 1.57 ml for FI-ETAAS analysis a limit of detection of 15 ng l(-1) was obtained for the combined procedure, with a relative standard deviation being not more than 4.9%. The method was applied to quantify the water soluble fraction of Pd in urban road dust. Extractions with a rain sample of pH 5.9 revealed that an average of 2.2% (n=8) of the total Pd present in urban road dust was water soluble. PMID- 17723582 TI - A pre-concentration procedure using coprecipitation for determination of lead and iron in several samples using flame atomic absorption spectrometry. AB - The present paper proposes a pre-concentration procedure for determination of lead and iron in several samples by flame atomic absorption spectrometry. In it, lead(II) and iron(III) ions are coprecipitated using the violuric acid-copper(II) system as collector. Afterwards, the precipitate is dissolved with 1M HNO3 solution and the metal ions are determined. The optimization step was performed using factorial design involving the variables: pH, violuric acid mass (VA) and copper concentration (Cu). Using the optimized experimental conditions, the proposed procedure allows the determination these metals with detection limits of 0.18 microg L(-1) for iron and 0.16 microg L(-1) for lead. The effects of foreign ions on the pre-concentration procedure were also evaluated and the results demonstrated that this method could be applied for determination of iron and lead in several real samples. The proposed method was successfully applied to the analysis of seawater, urine, mineral water, soil and physiological solution samples. The concentrations of lead and iron achieved in these samples agree well with others data reported in the literature. PMID- 17723583 TI - Application of liquid-phase microextraction to the analysis of trihalomethanes in water. AB - A liquid-phase microextraction method for the determination of trihalomethanes (THMs) including chloroform (CHCl3), bromodichloromethane (CHBrCl2), dibromochloromethane (CHBr2Cl) and bromoform (CHBr3) in water samples was developed, with analysis by gas chromatography-electron capture detection (GC ECD). After the determination of the most suitable solvent and stirring rate for the extraction, several other parameters (solvent drop volume, extraction time and ionic strength of the sample) were optimized using a factorial design to obtain the most relevant variables. The optimized extraction conditions for 5 mL of sample volume in a 10 mL vial were as follows: n-hexane an organic solvent; a solvent drop volume of 2 microL; an extraction time of 5.0 min; a stirring rate of 600 rpm at 25 degrees C; sample ionic strength of 3M sodium chloride. The linear range was 1-75 microg L(-1) for the studied THMs. The limits of detection (LODs) ranged from 0.23 microg L(-1) (for CHBr2Cl) to 0.45 microg L(-1) (for CHCl3). Recoveries of THMs from fortified distilled water were over 70% for a fortification level of 15 microg L(-1), and relative standard deviations of the recoveries were below 5%. Real samples collected from tap water and well water were successfully analyzed using the proposed method. The recovery of spiked water samples was from 73% to 78% with relative standard deviations below 7%. PMID- 17723584 TI - Analysis of charge transport in gels containing polyoxometallates using methods of different sensitivity to migration. AB - Two methods have been used for examination of transport of charge in gels soaked with DMF and containing dissolved polyoxometallates. The first method is based on the analysis of both Cottrellian and steady-state currents and therefore is capable of giving the concentration of the electroactive redox centres and their transport (diffusion-type) coefficient. The second method provides the real diffusion coefficients, i.e. transport coefficients free of migrational influence, for both the substrate and the product of the electrode reaction. Several gels based on poly(methyl methacrylate), with charged (addition of 1 acrylamido-2-methyl-2-propanesulphonic acid to the polymerization mixture) and uncharged chains, have been used in the investigation. The ratio obtained for the diffusion coefficient (second method) and transport coefficient (first method) was smaller for the gels containing charged polymer chains than for the gels with uncharged chains. In part these changes could be explained by the contribution of migration to the transport of polyoxomatallates in the gels. However, the impact of the changes in the polymer-channel capacity at the electrode surface while the electrode process proceeds was also considered. These structural changes should affect differently the methods based on different time domains. PMID- 17723585 TI - An absorbance-based micro-fluidic sensor for diffusion coefficient and molar mass determinations. AB - The H-Sensor reported herein is a micro-fluidic device compatible with flow injection analysis (FIA) and high performance liquid chromatography (HPLC). The device detects analytes at two separate off-chip absorbance flow cells, providing two simultaneous absorbance measurements. The ratio of these two absorbance signals contains analyte diffusion coefficient information. A theoretical model for the sensing mechanism is presented. The model relates the signal Ratio to analyte diffusion coefficient. The model is qualitatively evaluated by comparing theoretical and experimental signal Ratio values. Experimental signal Ratios were collected via FIA for a variety of analytes, including sodium azide, benzoic acid, amino acids, peptides, and proteins. Measuring absorbance at multiple wavelengths provides higher order data allowing the analyte signals from mixtures to be deconvolved via classical least squares (CLS). As a result of the H-Sensor providing two simultaneous signals as a function of time for each sample injection, two simulated second-order HPLC chromatograms were generated using experimental H-Sensor data. The chemometric deconvolution method referred to as the generalized rank annihilation method (GRAM) was used to demonstrate chromatographic and spectroscopic deconvolution. GRAM also provides the signal Ratio value, therefore simultaneously obtaining the analyte diffusion coefficient information during deconvolution. The two chromatograms successfully serve as the standard and unknown for the GRAM deconvolution. GRAM was evaluated on chromatograms at various chromatographic resolutions. GRAM was found to function to a chromatographic resolution at and above 0.25 with a percent quantitative error of less then 10%. PMID- 17723586 TI - Highly selective determination of methylmercury with methylmercury-imprinted polymers. AB - Methylmercury-imprinted and non-imprinted polymers were prepared by formation monomer complex of methylmercury with (4-ethenylphenyl)-4-formate-6-phenyl-2,2' bipyridine and thermally polymerizing with divinylbenzene (crosslinker) in the presence of 2,2'-azobisisobutyronitrile as initiator and subsequently leached with the acidic thiourea solution (1.0 mol L(-1) of thiourea and 4.0 mol L(-1) of HCl). In the same way, non-imprinted copolymers were prepared without methylmercury chloride added. The separation and preconcentration characteristics of the polymers for methylmercury were investigated by batch and column procedures. The results demonstrated that the methylmercury-imprinted polymers had higher adsorption capacity (170 micromol g(-1) of dry microbeads) and good selectivity for methylmercury compared to non-imprinted polymers. The distribution ratio (D) values of the methylmercury-imprinted polymers increased for methylmercury with respect to both D values of Hg(II), Cu(II), Zn(II), Cd(II) and non-imprinted polymers. The relatively selective factor (alpha(r)) values of CH3Hg+/Hg(II), CH3Hg+/Cu(II), CH3Hg+/Zn(II), and CH3Hg+/Cd(II) are 24.0, 46.7, 50.7, and 40.2, which are greater than 1. The methylmercury-imprinted polymers can be used at least twenty times with recoveries no less than 95%. Based on the packed columns with methylmercury-imprinted polymers, a highly selective solid phase extraction (SPE) and preconcentration method for methylmercury was developed. The metal ion imprinted polymer solid-phase extraction (MIIP-SPE) preconcentration procedure showed a linear calibration curve within concentration range from 0.093 to 22 microg L(-1). The detection limit and quantification limit were 0.041 and 0.093 microg L(-1) (3sigma) for cold vapor atomic absorption spectrometry (CVAAS). The relative standard deviation of the 10 replicate determinations was 3.5% for the determination of methylmercury in human hair sample. Determination of methylmercury in certified human hair sample (IAEA-086) and soil certified reference material (CRM 580) demonstrated that the interfering substances in matrix had been almost removed during preconcentration. The methylmercury-imprinted polymers were good enough for methylmercury determination in matrixes containing components with similar chemical property such as Hg(II), Cu(II), Zn(II), and Cd(II). PMID- 17723587 TI - Column preconcentration of lead in aqueous solution with macroporous epoxy resin based polymer monolithic matrix. AB - The objective of this article was to investigate the feasibility of epoxy resin based monoliths prepared by stepwise polymerization and column preconcentration of metal ions using large-scale monolithic matrix. A novel macroporous polymer monolith matrix was prepared from epoxy resin (EP) and ethylenediamine (EDA) and pore-forming reagent (polyethylene glycol, PEG-1000) by in situ step-addition polymerization. The morphology of the resulting polymer monolith was characterized by scanning electron microscopy (SEM). A solid-phase extraction (SPE) cartridge prepared from a simple glass-tube was used for the preconcentration and determination of Pb(II) combined with flame atomic absorption spectroscopy (FAAS). The characteristics of the monoliths for the extraction of Pb(II) in aqueous solution were investigated. The experimental results showed that trace Pb(II) ions could be quantitatively preconcentrated in the pH range of 4.0-9.0 with recoveries of >95%. The maximum static adsorption capacity of the monolith adsorbent was 106.8 mg g(-1). The column was eluted by 1.0 mol L(-1) HNO3 and recovery of Pb(II) was more than 97%. Moreover, the polymer monolith adsorbent shows superior reusability and stability. The precision and the accuracy of the proposed procedure were satisfactory by analyzing a standard reference material and three natural water samples. It was shown that the EP-EDA monolith was suitable for the preconcentration of environmental Pb(II) as an ion-selective SPE adsorbent. PMID- 17723588 TI - Electrochemical detection of cysteine in a flow system based on reductive desorption of thiols from gold. AB - A simple strategy for cysteine determination using flow-injection analysis with electrochemical detection is described. The approach is based on the chemisorptions reactions of the sulfur moiety of cysteine upon polycrystalline gold electrodes and its subsequent reductive desorption. The electrochemical measurements were accomplished by the application of differential pulse voltammetry (DPV) for the operational optimization and pulsed electrochemical detection (PED) in combination with flow-injection analysis for the electrochemical detection as time function. The electroactive species could be adsorbed in a potential level (0.1 V versus SCE), at other (-0.6 V versus SCE) occurs their reductive desorption from the electrode, while the analytical current is recorded simultaneously, and a third potential step is applied to the complete regeneration of the gold electrode surface (-1.3 V versus SCE). The linear response range was observed between 1.0 x 10(-6) and 6.0 x 10(-6) mol L( 1) with a good reproducibility (R.S.D.<3.2%) and sensitivity (1.1 microA/microM). The repeatability (a series of 27 continuous FIA peaks of 5. 0 micromol L(-1) of cysteine) was 3.8 % and the limit of detection was 5.0 x 10(-7) mol L(-1). The sample throughput was 23 samples per hour with a very high stability in its voltammetric response. The developed methodology was successfully used for the determination of cysteine in commercial supplementary food sample. PMID- 17723589 TI - A comparison of boron-doped diamond thin-film and Hg-coated glassy carbon electrodes for anodic stripping voltammetric determination of heavy metal ions in aqueous media. AB - The performance of boron-doped diamond (BDD) for the anodic stripping voltammetric (ASV) determination of heavy metal ions (Zn2+, Cd2+, Pb2+, Cu2+, Ag+) was compared with that of Hg-coated glassy carbon (Hg-GC). Hg has historically been the electrode of choice for ASV but there is an ongoing search for alternate electrodes and diamond is one of these. Despite the fundamentally different nature of the metal reduction and oxidation reactions on these two electrodes, BDD provides as good or superior analytical detection figures of merit when compared to Hg. The stripping peak potentials for all the metals studied were similar at both electrodes indicating that BDD is as active as Hg for metal phase formation and oxidation. Due to the more heterogeneous chemical and electrical properties across the BDD surface, the stripping peaks were broader and more asymmetric than they were for Hg-GC. The linear dynamic range for BDD was three to four orders of magnitude (r2>0.995), similar to Hg-GC, but the sensitivity for BDD was three to five times lower. However, the lower background current and noise for BDD enabled detection limits as low as those seen for Hg-GC. The minimum concentration of each metal ion detectable (S/N> or =3) with BDD was in the mid to low ppb range (e.g., 50 ppb Zn2+, 1.0 ppb Cd2+, 5.0 ppb Pb2+, 10 ppb Cu2+ and 1.0 ppb Ag+). BDD exhibited an electrode-to electrode and run-to-run variability of less than 5%, which is comparable to that for Hg-GC. The possibility of incomplete metal oxidation and metal phase detachment from BDD was investigated using double step chronoamperometry. Neither of these processes was found to occur to any appreciable extent. The results demonstrate that BDD is a viable alternate electrode to Hg for ASV. PMID- 17723590 TI - Electrochemical behaviour of isatin at a glassy carbon electrode. AB - The electrochemical behavior of isatin--a molecule with a broad range of applications in synthetic, biological and clinical activity--has been investigated over a wide pH range at a glassy carbon electrode (GCE) using cyclic, square wave and differential pulse voltammetry. The oxidation of isatin is an irreversible process, pH dependent and occurs with the formation of a main oxidation product that strongly adsorbs on the electrode surface. The reduction of isatin is also a pH dependent irreversible process. Cyclic voltammograms show two consecutive charge transfer reactions. The diffusion coefficient of isatin was calculated in pH 7.0 phosphate buffer to be D(0)=4.9 x 10(-7) cm2 s(-1). The limit of detection obtained in a solution of pH 7.0 phosphate buffer was LOD=0.194 microM, based on three times the noise level. PMID- 17723591 TI - A cerium(III) selective polyvinyl chloride membrane sensor based on a Schiff base complex of N,N'-bis[2-(salicylideneamino)ethyl]ethane-1,2-diamine. AB - A polyvinyl chloride (PVC) based membrane sensor for cerium ions was prepared by employing N,N'-bis[2-(salicylideneamino)ethyl]ethane-1,2-diamine as an ionophore, oleic acid (OA) as anion excluder and o-nitrophenyloctyl ether (o-NPOE) as plasticizer. The plasticized membrane sensor exhibits a Nernstian response for Ce(III) ions over a wide concentration range (1.41 x 10(-7) to 1.0 x10 (-2) M) with a limit of detection as low as 8.91 x 10(-8) M. It has a fast response time (<10s) and can be used for 4 months. The sensor revealed a very good selectivity with respect to common alkali, alkaline earth and heavy metal ions. The response of the proposed sensor is independent of pH between 3.0 and 8.0. It was used as an indicator electrode in potentiometric titration of fluoride, carbonate and oxalate anions and determination of cerium in simulated mixtures. PMID- 17723593 TI - The second chemiluminescence emission of luminol-periodate-menadione sodium bisulfite system and its analytical application. AB - In this paper, a new chemiluminescence phenomenon described as the second chemiluminescence emission was observed when menadione sodium bisulfite was injected into a reaction mixture of luminol and potassium periodate, in which luminol was oxidized by excess amount of potassium periodate for about 24h. The mechanism of the second chemiluminescence emission was proposed based a series of experiments. Moreover, our experiment discovered that the second chemiluminescence intensity was a linear function of the concentration of menadione sodium bisulfite in the range of 2 x 10(-9) to 4 x 10(-5) g L(-1). Based on this phenomenon, a new flow-injection method for the determination of menadione sodium bisulfite has been established. PMID- 17723592 TI - Electrogenerated chemiluminescence detection for deoxyribonucleic acid hybridization based on gold nanoparticles carrying multiple probes. AB - A novel sensitive electrogenerated chemiluminescence (ECL) method for the detection deoxyribonucleic acid (DNA) hybridization based on gold nanoparticles carrying multiple probes was developed. Ruthenium bis(2,2'-bipyridine)(2,2' bipyridine-4,4'-dicarboxylic acid)-N-hydroxysuccinimide ester (Ru(bpy)2(dcbpy)NHS) was used as a ECL label and gold nanoparticle as a carrier. Probe single strand DNA (ss-DNA) was self-assembled at the 3'-terminal with a thiol group to the surface of gold nanoparticle and covalently labeled at the 5' terminal of a phosphate group with Ru(bpy)2(dcbpy)NHS and the resulting conjugate, (Ru(bpy)2(dcbpy)NHS)-ss-DNA-Au, was taken as a ECL probe. When target analyte ss-DNA was immobilized on a gold electrode by self-assembled monolayer technique and then hybridized with the ECL probe to form a double-stranded DNA (ds-DNA), a strong ECL response was electrochemically generated. The ECL intensity was linearly related to the concentration of the complementary sequence (target ss-DNA) in the range from 1.0 x 10(-11) to 1.0 x 10(-8) mol L(-1), and the linear regression equation was S=57301+4579.6 lg C (unit of C is mol L(-1)). A detection limit of 5.0 x 10(-12) mol L(-1) for target ss-DNA was achieved. The ECL signal generated from many reporters of ECL probe prepared is greatly amplified, compared to the convention scheme which is based on one reporter per hybridization event. PMID- 17723594 TI - A selective fluorescence-on reaction of spiro form fluorescein hydrazide with Cu(II). AB - The spiro form fluorescein hydrazide (1) bearing a cleavable active bond is characterized as a highly selective and sensitive fluorescence probe for Cu2+. In 0.01 M Tris-HCl buffer (pH 7.2), the probe displays a highly selective fluorescence-on response to Cu2+ only, instead of other common metal ions. The reaction mechanism has been explored and proposed as that the hydrazide group of 1 recognizes and binds Cu2+, and the subsequent complexation of Cu2+ promotes hydrolytic cleavage of the amide bond, causing the release of fluorophore (fluorescein) and thereby the retrievement of fluorescence. Conditions for fluorescence measurement were optimized, generating a calibration curve that is linear over the concentration range of 0.1-10 microM Cu2+. The detection limit for Cu2+ is 64 nM based on 11 blank determinations (k=3), also showing a highly sensitive feature. The fluorescence-on reaction described here has been used for the determination of trace Cu2+ in real biological fluids with satisfactory results. PMID- 17723595 TI - Calibration of Phen Green for use as a Cu(I)-selective fluorescent indicator. AB - Conditional stability constants for the Cu-sensitive fluorescent dye Phen Greentrade mark SK (PGSK) were determined for complexes containing both Cu(I) and Cu(II). Experimental conditions were optimized to minimize oxidation of Cu(I) to Cu(II). A binding constant of 10(11.38) for PGSK and Cu(I) was determined using chloride as the competing ligand and an iterative procedure involving equilibrium calculations to fit experimental data. The new constant was tested by evaluating PGSK fluorescence in the presence of the strong Cu(I)-ligand neocuproine and thiourea. There was good agreement between experimental data and changes in fluorescence predicted by calculations using the new constant and published constants for the competing ligands. Using EDTA to buffer the free ion concentration of Cu2+, the conditional stability constant of PGSK with Cu(II) was measured to be 10(9.8). Both of these new constants are significantly higher than previously published values. Finally PGSK was used to examine the kinetics of Cu(I) dissociation from the biologically important ligand glutathione. PMID- 17723596 TI - Laser-induced breakdown spectroscopy for quantitative spectrochemical analysis of geological materials: effects of the matrix and simultaneous determination. AB - A microscopic laser-induced breakdown spectrometer was used to evaluate the analytical matrix effect commonly observed in the analysis of geological materials. Samples were analyzed in either the powder or pressed pellet forms. Calibration curves of a number of iron and aluminum compounds showed a linear relationship between the elemental concentration and peak intensity. A direct determination of elemental content can thus be made from extrapolation on these calibration curves. To investigate matrix effects, synthetic model samples were prepared from various iron and aluminum compounds spiked with SiO2 and CaCO3. The addition of these matrices had a pronounced analytical effect on those compounds prepared as pressed pellets. However, results indicated the absence of matrix effects when the samples were presented to the laser as loose powders on tape and results were compared to certified values, indicating the reliability of this approach for accurate analysis, provided the sample particle diameters are greater than approximately 100 microm. Finally, the simultaneous analysis of two different elements was demonstrated using powders on tape. PMID- 17723597 TI - Comparative analysis of the volatile components in cut tobacco from different locations with gas chromatography-mass spectrometry (GC-MS) and combined chemometric methods. AB - A combined approach of subwindow factor analysis and orthogonal projection resolution was used to analyze the volatile components of cut tobacco samples from different sources. After extracted with simultaneous distillation and extraction method, the volatile components in cut tobacco from five different locations were detected by GC-MS. Then, the qualitative and quantitative analysis of the volatile components of cut tobacco from Changde area was completed with the help of subwindow factor analysis resolving two-dimensional original data into pure mass spectra and chromatograms. One hundred and two volatile components among 138 separated peaks were identified and quantified, accounting for about 88.90% of the total content. Finally, orthogonal projection method was used to extract the common peaks from different locations. Among the identified components, there were 74 components coexisting in five studied samples although the relative content of each component showed difference to some extent. The results showed a fair consistency in their GC-MS fingerprints. It was the first time to apply orthogonal projection method to compare different cut tobacco samples, and it reduced the burden of qualitative analysis as well as the subjectivity. The obtained results proved the combined approach powerful for the analysis of complex cut tobacco samples. The developed method can be used to compare the sameness and differences of cut tobacco from different sources and for quality control of cigarette production and materials. PMID- 17723598 TI - Establishment of a knowledge base for identification of residual solvents in pharmaceuticals. AB - A knowledge base for identification of residual solvents in pharmaceuticals has been established using gas chromatograph-mass spectrometry (GC-MS) and gas chromatograph-Fourier transform infrared spectrometry (GC-FTIR). Sixty solvents were studied according to the guideline for residual solvents regulated by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The standard mass spectra library, the limit of detection (LOD) mass spectra library, the standard vapor phase infrared spectra library, and the limit of detection (LOD) vapor-phase infrared spectra library were established and constituted the knowledge base. Using the knowledge base, the problem of qualitation, which was the difficulty of determining residual solvents, can be resolved. PMID- 17723599 TI - Determination of biogenic amines in apples and wine with 8-phenyl-(4-oxy-acetic acid N-hydroxysuccinimide ester)-4, 4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a diaza-s-indacene by high performance liquid chromatography. AB - A precolumn-derivatization high performance liquid chromatographic method for biogenic amine analysis has been developed. Derivatization of biogenic amines was performed with a new fluorescent reagent, 8-phenyl-(4-oxy-acetic acid N hydroxysuccinimide ester)-4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s indacene (TMPAB-OSu), which was synthesized in our lab. The derivatization conditions and the influence of elution composition on the separation were investigated. In pH 8.5 H3BO3-Na2B4O7 media, the reaction of biogenic amines with TMPAB-OSu completed at 45 degrees C for 5 min. The labeled biogenic amines were separated on an ZORBAX Eclipse XDB-C8 column (150 mm x 4.6 mm, 5 microm) and detected with fluorescence at excitation and emission wavelengths of 497 and 509 nm, respectively. Detection limits of biogenic amines were 0.1-4 nmol L(-1), at a signal-to-noise ratio of 3. The proposed method has been applied to the quantitative determination of spermine, phenethylamine, spermidine, cadaverine and putrescine in pericarp and pulp of mature and immature apples and wine with recoveries of 95-102% and R.S.D. of 0.7-3.9. PMID- 17723601 TI - Cadmium bioavailability and speciation using the permeation liquid membrane. AB - The permeation liquid membrane (PLM) technique was used to evaluate cadmium speciation in media resembling natural freshwaters. A planar sheet PLM system was characterized by measuring Cd fluxes in the absence and presence of complexing agents such as citrate, malonate, nitrilotriacetate and the Suwannee River standard humic acid. Comparison with theoretical speciation calculations and the results of a Cd2+ selective electrode, showed that free Cd was correctly measured using the planar sheet PLM within the studied concentration range, i.e. 10(-8) to 10(-4) M. The effect of pH and potentially co-transported ions on Cd transport through the PLM was also studied. An example of the ability of the hollow-fiber PLM (HFPLM) to measure free Cd in the nM range is also presented. In order to evaluate the usefulness of the technique as a predictor of bioavailability, Cd PLM measurements (fluxes) were compared to Cd biouptake (internalization flux) for a freshwater alga, Chlorella kesslerii, in the absence and presence of SRHA. The use of PLM measurements is shown to be an attractive tool to better understand Cd biouptake. PMID- 17723600 TI - A monoclonal antibody-based time-resolved fluoroimmunoassay for chloramphenicol in shrimp and chicken muscle. AB - A time-resolved fluoroimmunoassay (TR-FIA) for determination of chloramphenicol (CAP) in shrimp and chicken muscle was developed. The method was based on a direct competitive immunoassay using europium-labeled anti-CAP monoclonal antibody (MAb) and CAP-ovalbumin as coated antigen. The limit of detection was 0.05 ng g(-1) and limit of quantification was 0.1 ng g(-1). Recoveries ranged from 101.2 to 112.5% for shrimp and 104.9 to 115.3% for chicken muscle at spiked levels of 0.1-5 ng g(-1), with intra-assay and inter-assay variations 8.7-14.6 and 9.6-17.8%, respectively. The results obtained by the TR-FIA and ELISA correlated well. The established TR-FIA was validated for the determination of incurred shrimp samples and confirmed by gas chromatography with microcell electron capture detector (GC-microECD). PMID- 17723602 TI - Speciation measurements of uranium in alkaline waters using diffusive gradients in thin films technique. AB - This work investigated the application of diffusive gradients in thin films technique (DGT) to uranium speciation measurements in natural water. Two binding phases were examined, a commercially available affinity membrane, Whatman DE 81 (DE 81), with amino binding functional groups and the conventionally used Chelex 100 beads imbedded polyacrylamide hydrogel (Chelex) with iminodiacetate functional groups. The DGT devices assembled with the binding phases of DE 81 (DE 81 DGT) and Chelex gel (Chelex DGT) were tested both in synthetic river water solutions and in local river water. DE 81 DGT and Chelex DGT measured 80% and 75% of the total uranium in synthetic river water solution, respectively, and measured 73% and 60% of the total uranium in St. Lawrence River, Canada, respectively. The binding properties of the DE 81 membrane and Chelex gel for uranium, and the diffusion of uranyl complexes in the polyacrylamide gel (PAM) were also studied. PMID- 17723603 TI - Patterning chemical stimulation of reconstructed neuronal networks. AB - A spatially resolved delivery of substances integrated with cell culture substrates shows promise for application in pharmacological assays, bioanalytical studies on cell signaling pathways and cell-based biosensors, where control over the extracellular biochemical environment with a cellular resolution is desirable. In this work, we studied a biohybrid system where rat embryonic cortical neuronal networks are reconstructed on microstructured silicon chips and interfaced to microfluidics. The design of cell-cell and cell-medium interactions in confined geometries is presented. We developed an aligned microcontact printing technique (AmicroCP) for poly(lysine)-extracellular matrix proteins on microstructured chips, which allows a high degree of geometrical control over the network architecture and alignment of the neuronal network with the microfluidic features of a substrate. Spatially resolved on-chip delivery of compounds with a cellular resolution is demonstrated by chemical stimulation of patterned rat cortical neurons within a network with a number of solutions of excitatory neurotransmitter glutamate delivered via microfluidics. The combination of the system described with a patch-clamp technique allowed both modulation of the biochemical environment on a cellular level and the monitoring of electrophysiological properties in the reconstructed rat embryonic cortical networks changed by this microenvironment. PMID- 17723604 TI - Partial least squares-based multivariate spectral calibration method for simultaneous determination of beta-carboline derivatives in Peganum harmala seed extracts. AB - The partial least squares regression method has been applied for simultaneous spectrophotometric determination of harmine, harmane, harmalol and harmaline in Peganum harmala L. (Zygophyllaceae) seeds. The effect of pH was optimized employing multivariate definition of selectivity and sensitivity and best results were obtained in basic media (pH>9). The calibration models were optimized for number of latent variables by the cross-validation procedure. Determinations were made over the concentration range of 0.15-10 microg mL(-1). The proposed method was validated by applying it to the analysis of the beta-carbolines in synthetic quaternary mixtures of media at pH 9 and 11. The relative standard errors of prediction were less than 4% in most cases. Analysis of P. harmala seeds by the proposed models for contents of the beta-carboline derivatives resulted in 1.84%, 0.16%, 0.25% and 3.90% for harmine, harmane, harmaline and harmalol, respectively. The results were validated against an existing HPLC method and it no significant differences were observed between the results of two methods. PMID- 17723606 TI - Continuous multi-element (Cu, Mn, Ni, Se) monitoring in saline and cell suspension using on-line microdialysis coupled with simultaneous electrothermal atomic absorption spectrometry. AB - We have developed a microdialysis sampling technique coupled on-line with simultaneous electrothermal atomic absorption spectrometry (SIMAAS) for the continuous monitoring of copper (Cu), manganese (Mn), nickel (Ni), and selenium (Se) in saline solutions and in cell suspensions. These trace elements are considered to be those associated most significantly with oxidative stress in biological systems. We employed ultrapure saline (0.9% NaCl) as the perfusate and, thus, the dialysate samples contained a high concentration of salt in the matrix. The use of modifiers [Pd coupled with Mg(NO3)2] prevented the target elements from undergoing evaporation at a pyrolysis temperature of 1200 degrees C, a process that effectively eliminated interference from NaCl. The excellent linearity, detection limits, and precision of the SIMAAS technique allowed the Cu, Mn, Ni, and Se concentrations to be determined in saline. For the on-line microdialysis-SIMAAS system, the ultrapure saline was perfused at a flow rate of 1 microL/min. The probe recoveries of Cu, Mn, Ni, and Se in saline were 57.9, 65.0, 65.5, and 67.9%, respectively. A standard saline solution was measured continuously by the on-line system to ensure long-term stability; each measurement fell within a range of two standard deviations. We determined the on line spiked recoveries of Cu, Mn, Ni, and Se (101.3, 88.8, 91.3, and 98.5%, respectively) by adding a spiking standard into the stirred saline. The spiked recoveries (Cu, 37.5%; Mn, 3.8%; Ni, 71.1%; Se, 33.8%) were also determined through on-line spiking of a standard into the stirred cell suspension; these values demonstrate that Cu, Mn, and Se were depleted in the cell suspension, but Ni was not. The use of this on-line microdialysis-SIMAAS system permitted the in situ, dynamic, and continuous monitoring of Cu, Mn, Ni, and Se in cell suspensions at a temporal resolution of 20 min. PMID- 17723607 TI - Interlaboratory study to improve the quality of trace element determinations in rainwater. AB - This is the first publication which describes the development of a reference material (RM) for the determination of 11 trace elements (Cu, Pb, Mn, Ni, Zn, Fe, Cd, Co, V, As and Al) in rainwater at microgram per liter concentrations. An interlaboratory comparison study for the determination of trace elements in rainwater was carried out for material performance studies to establish analyte concentrations with a stated uncertainty. Fifteen reputed laboratories from Asia, Europe and North America participated in the study. These laboratories used their regular in-house methods to analyze the rainwater samples. The aim of this study is to establish concentration levels of trace elements in rainwater based on interlaboratory study results. Details of the production, homogeneity and stability of the reference sample are given in this article. The organization of the study and the quality assurance measures undertaken at the organizer's laboratory are described. The analytical results obtained from individual laboratories and the analytical methods used for the determination of trace elements in rainwater are discussed. Based on the results obtained from the intercomparison study, certified values as well as informative values are assigned to the 11 trace elements in rainwater. PMID- 17723608 TI - Studies on electrochemical behaviors of acyclovir and its voltammetric determination with nano-structured film electrode. AB - A multi-wall carbon nanotubes (MWNTs)-dihexadecyl hydrogen phosphate (DHP) film coated glassy carbon electrode (GCE) was fabricated, and the electrochemical behaviors of acyclovir on the MWNTs-DHP film-coated GCE were investigated by using cyclic voltammetry (CV), linear sweep voltammetry (LSV), electrochemical impedance spectroscopy (EIS) and chronocoulometry (CC). The oxidation peak current of acyclovir increased significantly and the peak potential shifted negatively at the MWNTs-DHP film-modified GCE, compared with that at a bare GCE. The results showed that this nano-structured film electrode exhibited excellent enhancement effects on the electrochemical oxidation of acyclovir. Consequently, a simple and sensitive electroanalytical method was developed for the determination of acyclovir. The oxidation peak current was proportional to the concentration of acyclovir from 8.0 x 10(-8) to 1.0 x 10(-5) mol/L. The detection limit was about 3.0 x 10(-8) mol/L for 60s accumulation at 0.00 V. The proposed method was demonstrated by using acyclovir tablets and the result was satisfying. PMID- 17723609 TI - Microwave assisted sample preparation for determining water-soluble fraction of trace elements in urban airborne particulate matter: evaluation of bioavailability. AB - The feasibility of using two different microwave-based sample preparation methods was investigated to determine the total and water-soluble trace metal fraction in airborne particulate matter. The extraction techniques were then applied to urban particulate matter of different sizes in order to evaluate their bioavailability of associated trace metals. While a combination of HNO3-HF-H2O2 was used for the total trace metal fraction of particulate matter, water was employed for the microwave-assisted extraction of water-soluble trace metal fractions. Inductively coupled plasma-mass spectrometry (ICP-MS) was used for the analysis of trace elements. The experimental protocol for the microwave assisted digestion was established using two different SRMs (1648, urban particulate matter and 1649a, urban dust). In the case of water-soluble trace metal fraction, the quantities extracted from the SRMs were compared between ultrasonic and microwave-assisted extractions, and there was a good agreement between the two extraction methods. Blanks values and limits of detection (LODs) for total and water-soluble trace metal concentrations were determined for three different filter substrates (Teflon, Zeflour, and Quartz). Subsequently, the proposed digestion method was evaluated for its extraction efficiency with these filter substrates. Finally, the real-world application of the proposed microwave-based sample preparation methods was demonstrated by analyzing trace elements in airborne particulate samples collected from different outdoor environments in Singapore. The solubility of 11 trace elements detected in the particulate samples is quantified. PMID- 17723611 TI - Treatment of colored effluent of the textile industry in Bangladesh using zinc chloride treated indigenous activated carbons. AB - The adsorption of colored compounds from the textile dyeing effluents of Bangladesh on granulated activated carbons produced from indigenous vegetable sources by chemical activation with zinc chloride was studied. The most important parameters in chemical activation were found be the chemical ratio of ZnCl2 to feed (3:1), carbonization temperature (450-465 degrees C) and activation time (80 min). The adsorbances at 511 nm (red effluent) and 615 nm (blue effluent) were used for color estimation. It is established that at optimum temperature (50 degrees C), time of contact (30-40 min) and adsorbent loading (2 g l(-1)), activated carbons developed from Segun saw-dust and water hyacinth showed substantial capability to remove coloring materials from the effluents. It is observed that adsorption of reactive dyes by all sorts of activated carbons is higher than disperse dyes. It is explained that activated carbon, because of its acidic nature, can better adsorb reactive dye particles containing large number of nitrogen sites and -SO3Na group in their structure. The use of carbons would be economical, as saw-dust and water hyacinth are waste products and abundant in Bangladesh. PMID- 17723610 TI - Development of new cleanup method of polychlorinated dibenzo-p dioxins/dibenzofurans in fish by freezing-lipid filtration. AB - Freezing-lipid filtration as a new method has been developed for the rapid determination of polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDDs/Fs) in biological samples. This method can effectively reduce the time of sample pretreatment, labor and amount of solvents compared with conventional methods. By freezing-lipid filtration procedure, about 90% of lipids in extract could be removed without any significant loss of PCDD/Fs. For further cleanup of extracts after freezing-lipid filtration, automatic parallel LC columns including silica gel, alumina and carbon columns were applied. During automatic parallel LC columns cleanup, most of co-extracted interferences such as residue lipids and fatty acids could be eliminated and dioxins could be separated from many other dioxin-like congeners such as polychlorinated biphenyls by this procedure. The extracts after cleanup were analyzed by high-resolution gas chromatography (HRGC)/high-resolution mass spectrometry (HRMS) using an isotope dilution method. The average recoveries and relative standard deviation (R.S.D.) of 17 native congeners in the spiked fish samples at 8-80 pg/g (n=3) were ranged between 85.3 and 117.2% and 5.7-20.3%, respectively. PMID- 17723612 TI - Analysis of volatile compounds emitted from fresh Syringa oblata flowers in different florescence by headspace solid-phase microextraction-gas chromatography mass spectrometry. AB - In this study, a simple and solvent-free method was developed for determination of the volatile compounds from fresh flowers of Syringa oblata using headspace solid-phase microextraction and gas chromatography-mass spectrometry. The SPME parameters were studied, the optimum conditions of a 65mum polydimethylsiloxan/divinylbenezene (PDMS/DVB), extraction temperature of 25 degrees C and extraction time of 30 min were obtained and applied to extraction of the volatile compounds emitted from fresh flowers of S. oblata. The volatile compounds released from fresh flowers of S. oblata were separated and identified by GC-MS. Lilac aldehyde A, lilac aldehyde B, lilac aldehyde C, lilac aldehyde D, lilac alcohol A, lilac alcohol B, lilac alcohol C, lilac alcohol D, alpha-pinene, sabinene, beta-pinene, myrcene, d-limonene, eucalyptol, cis-ocimene, benzaldehyde, terpinolene, linalool, benzene acetaldehyde, alpha-terpineol, p methoxyanisole, p-anisaldehyde, (Z,E)-alpha-farnesene and (E,E)-alpha-farnesene were the most abundant volatiles released from fresh flowers of S. oblata var. alba. The relative contents of main volatile fragrance were found to be different in emissions from two varieties of S. oblata flowers (white or purple in color). The four isomers of lilac alcohol and four isomer lilac aldehyde were the characteristic components of the scent of fresh flowers of S. oblata. The main volatile fragrance from fresh flowers of S. oblata var. alba in different florescence ((A) flower buds; (B) at the early stage of flower blooming; (C) during the flower blooming; (D) at the end of flower blooming; (E) senescence) were studied in this paper. The results demonstrated that headspace SPME-GC-MS is a simple, rapid and solvent-free method suitable for analysis of volatile compounds emitted from fresh flowers of S. oblata in different florescence. PMID- 17723613 TI - Enantiomeric quantification of (S)-(+)-methamphetamine in urine by an immunoaffinity column and liquid chromatography-electrospray-mass spectrometry. AB - A method using an immunoaffinity column (IAC) and liquid chromatography electrospray ionization mass spectrometry (LC/MS) for on-line detecting the presence of MA in the effluent was developed for the quantitative and enantiomeric determination of (S)-(+)-methamphetamine (d-MA) in urine. The IAC was made in our laboratory and utilized in the LC/MS to simultaneously extract and separate enantiomers of MA from urine samples. An aqueous ammonium acetate buffer was used as the mobile phase. Urine samples were spiked with racemic deuterated methamphetamine (MA-d14) as internal standard (IS), filtered through a membrane, and injected into the LC/MS without any further pre-treatment. Protonated molecular ion of MA and MA-d(14) (m/z 150 and 164) were isolated and further fragmented, the respective product ions, m/z 119 and 130, were collected for quantitative determination. This is an improvement of our previous method (A.C. Lua, Tsong-Yung Chou, J. Chromatogr. A 967 (2002) 191). In the previous method, MA was separated with HPLC, the efflux was fractionated and each fraction was either determined with an immunoassay or GC/MS. Monitoring of MA in the efflux is tedious and time consuming. Urine samples spiked with different concentrations of d-MA were measured by this method. A linear relationship exists in the 150-1050 ng/mL range, and the detection limit (defined as signal-to-noise ratio 3) of d-MA was determined to be 18 ng/mL. The linearity of the method for d MA can be described by the equation (Y=1.415 x 10(-3)X+0.034, correlation coefficient: r2=0.999). Within run, accuracy and precision (n=6, relative error: 7.2 to +4.0% and relative standard deviation: 3.8-9.3%) of the method are fairly good. PMID- 17723614 TI - Urinary polyamines and N-acetylated polyamines in four patients with Alzheimer's disease as their N-ethoxycarbonyl-N-pentafluoropropionyl derivatives by gas chromatography-mass spectrometry in selected ion monitoring mode. AB - Simultaneous determination of putrescine, cadaverine, spermidine, spermine, N1 acetylputrescine, N1-acetylcadaverine, N1-acetylspermidine, N8-acetylspermidine and N1-acetylspermine in aqueous samples was achieved as their N-ethoxycarbonyl-N pentafluoropropionyl derivatives by gas chromatography-mass spectrometry (GC-MS) in selected ion monitoring (SIM) mode. The overall GC-SIM-MS method was linear (r> or =0.9987), repetitive (% relative standard deviation=1.3-6.4), and accurate (% relative error=-2.1-8.6). As compared to normal subjects, the levels of putrescine, N1-acetylspermine and spermine were significantly elevated while the levels of N1-acetylputrescine, N1-acetylcadaverine and N1-acetylspermidine were markedly reduced in all four Alzheimer's disease (AD) patients. When star symbol plotting was applied to the normalized levels of nine polyamines relative to the corresponding normal mean values, each star pattern of the AD patients was deformed, thus being readily distinguishable from the nonagon shape of the normal group average. PMID- 17723615 TI - Combination of liquid-phase hollow fiber membrane microextraction with gas chromatography-negative chemical ionization mass spectrometry for the determination of dichlorophenol isomers in water and urine. AB - A method for the determination of trace amount of dichlorophenol isomers in urine samples using the combination of liquid-phase hollow fiber microextraction (LPME HF) with gas chromatography-negative chemical ionization mass spectrometry (GC NCI-MS) has been demonstrated. The method has been optimized with respect to several parameters including the effects of negative chemical ionization (NCI) reagent pressure, the hollow fiber length, extraction time, stirring rate, sample pH and salt concentration for the determination of dichlorophenol isomers in water. The correlation coefficient (r2) of the calibration curves for 2,5 dichlorophenol, 2,3-dichlorophenol, 2,6-dichlorophenol, 3,5-dichlorophenol and 3,4-dichlorophenol were 0.988, 0.981, 0.985, 0.971 and 0.994, respectively. The average recovery rates for 2,5-dichlorophenol, 2,3-dichlorophenol, 2,6 dichlorophenol, 3,5-dichlorophenol and 3,4-dichlorophenol were 0.97, 0.93, 0.96, 0.95 and 0.95, respectively (n=3 for each dichlorophenol) indicate that the methodology is feasible for the determination of trace amounts of dichlorophenol isomers in water and urine samples. Limits of detection (LOD) have been found to be in the range of 5-20 ng/ml. In addition, differentiation of the five dichlorophenol isomers is an easy task using the current approach of combining LPME-HF with NCI-GC-MS technique since they exhibit different NCI spectra. PMID- 17723617 TI - Surface plasmon resonance immunosensor for histamine based on an indirect competitive immunoreaction. AB - The use of a surface plasmon resonance immunosensor for the analysis of histamine (beta-imidazole ethylamine) is described. The method is based on an indirect competitive reaction of an anti-histamine antibody in a sample solution with histamine immobilized on a sensor chip and with histamine in the sample solution. A sensor chip immobilized with histamine was prepared using a self-assembly monolayer of 11-mercaptoundecanoic acid (11-MUA) as an anchor membrane, followed by an amino-coupling reaction with histamine after activation of the 11-MUA layer on the sensor chip by treatment with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide. The sensor chip can be reused, after regeneration with a 10mM HCl solution, which dissociates the anti-histamine antibody complex from histamine on the sensor chip. The affinity constants for the immunocomplex of the anti-histamine antibody with histamine in the solution and for that of the anti-histamine antibody with histamine immobilized on the sensor chip were calculated to be 1.5 x 10(7) and 7.2 x 10(5) M(-1), respectively, by assuming a Langmuir-type adsorption of the anti-histamine antibody to histamine immobilized on the sensor chip. The detection limit of the method was determined to be 3ppb. PMID- 17723616 TI - Piezoelectric quartz crystal sensor for rapid analysis of pirimicarb residues using molecularly imprinted polymers as recognition elements. AB - A new piezoelectric quartz crystal (PQC) sensor using molecularly imprinted polymer (MIP) as sensing material has been developed for fast and onsite determination of pirimicarb in contaminated vegetables. Three MIPs particles have been prepared by conventional bulk polymerization (MIP-B) and precipitation polymerization in either acetonitrile (MIP-P1) or chloroform (MIP-P2). MIP-P2, with uniform spherical shape and mean diameter at about 50 nm, has shown the best performance as the sensing material for PQC sensor. The sensor fabricated with MIP-P2 can achieve a steady-state response within 5 min, a very short response time as compared to MIPs-coated PQC sensor reported in the literature. The sensor developed exhibits good selectivity (low response to those pesticides with similar structures to pirimicarb, such as atrazine, carbaryl, carbofuran and aldicarb) and high sensitivity to pirimicarb with a linear working range from 5.0 x 10(-6) to 4.7 x 10(-3) mol L(-1) (following a regression equation (r=0.9988) of -DeltaF=0.552+1.79 x 10(6) C), a repeatability (R.S.D., n=5) of 4.3% and a detection limit (S/N=3, n=5) of 5 x 10(-7) mol L(-1). The MIP-coated PQC sensor developed is shown to provide a sensitive and fast method for onsite determination of pirimicarb in aqueous extract from contaminated vegetables with satisfactory recoveries from 96 to 103% and repeatability (R.S.D., n=5) from 4.6 to 7.1% at pirimicarb concentrations ranging from 8.0x10(-6) to 2.0 x 10(-4) mol L(-1). PMID- 17723618 TI - Use of beta-cyclodextrin bonded phase with s-triazine moiety in the spacer for separation of aromatic carboxylic acid isomers by high-performance liquid chromatography. AB - The separation and retention behavior of five aromatic carboxylic acid isomers was investigated by means of high-performance liquid chromatography (HPLC) using a beta-cyclodextrin bonded phase with s-triazine ring in the spacer. The influence of mobile phase pH on the retention was examined. The presence of s triazine moiety in the spacer enhances greatly the selectivity of the isomers of aromatic carboxylic acids. Baseline separations of the five aromatic carboxylic acid isomers were achieved. In particular, the isomers of toluic, aminobenzoic, nitrobenzoic and hydroxybenzoic acid were successfully and effectively separated. The chromatographic results indicate that, in addition to inclusion complexation, pi-pi interaction and hydrogen bonding interaction between the bonded phase and analytes play significant roles in the retention of these acid isomers. Different elution orders were observed for these acidic solutes with different substituents. Possible retention mechanisms are discussed. PMID- 17723619 TI - Measurement of non-methane hydrocarbons in Taipei city and their impact on ozone formation in relation to air quality. AB - Air pollutants data from semi-continuous measurements at multiple sampling sites in Taipei metropolitan area of Taiwan was obtained by collecting air samples in canisters. The hydrocarbon composition was determined by using GC/MS and GC/FID. The air samples were pre-concentrated onto glass beads prior to separation by PLOT and DB-1 columns of GC. The method showed detection limit of <1 ppb and relative standard deviation in the range of 5-30% for different compounds. Aromatic hydrocarbons (toluene, benzene, etc.) and aliphatic hydrocarbons (ethylene, acetylene, propane, etc.) were correlated primarily to determine the source of emission. The estimated hydrocarbons were ranked according to their abundance and photochemical reactivity. The criteria pollutants, ozone and NO2 were measured by UV-differential optical absorption spectroscopy (UV-DOAS), and were utilized to determine the relative importance of non-methane hydrocarbons (NMHC) and significant contribution of NO2 in limiting ozone formation. The obtained results suggest that ozone formation in Taipei city is probably limited by the supply of non-methane hydrocarbons. The concentration profile of targeted pollutants was compared to other metropolitan areas to determine air quality and the pollutant sources. PMID- 17723620 TI - Sampling and analysis of volatile organics emitted from wastewater treatment plant and drain system of an industrial science park. AB - Volatile organic compounds (VOCs) were monitored in the different sections of a wastewater treatment plant (WWTP), the outlet of both the WWTP and rainfall water, and the downstream of the WWTP joining the river in the area or vicinity of an industrial science park located in Hsinchu, Taiwan. Levels of VOCs were determined by collecting air samples over several sampling points and analyzed using gas chromatography. Among VOCs identified in the drainage and effluent system in each season, acetone, isopropanol (IPA) and dimethyl sulfide (DMS) were the major emission species and maximum concentrations were 400.4, 22.8 and 641.2 ppbv, respectively. The ambient air and wastewater sample analysis from neighboring wastewater streams identified pollutants being discharged from unaccounted sources other than the industrial park. According to the 24h semi continuous monitoring data (27/7/2002-29/7/2002), the total VOC concentration was an average of 93 ppbv (acetone contributed approximately 78%) with a dramatic variation during the day and night. The emission rate of measured VOCs estimated using fixed box model projected an average of 2-4 microg m(-2) h(-1)) during the day and 9-17 microg m(-2) h(-1) during the night. In addition, the isopleth maps show that the acetone and DMS emissions influence adversely the nearby residential area located at less than 100 m downwind from the plant. Eventually, based on this study, an on-line monitoring and alerting system could be built for a long-term performance, and with regular information on the varying pollutants over time construction of a green strategy and creation of a sustainable environment can be achieved. PMID- 17723621 TI - Differentiation of herbs linked to "Chinese herb nephropathy" from the liquid chromatographic determination of aristolochic acids. AB - A HPLC method was developed and applied to analyze aristolochic acids (AA-I and AA-II) in Chinese medicinal herbs. The herb samples were extracted by using ultrasonication with the extraction efficiency of better than 82%. Extracts were then filtered and injected onto a C18 column eluting under a gradient program using methanol and water-containing 0.5% acetic acid. The method with the detection limits of 1.33 ng for AA-I and 7.29 ng for AA-II per injection was successfully applied for the analysis of traditional Chinese medicine (TCM) and related products and differentiation of Chinese medicinal herbs that have previously been misused and caused toxicological effects. The developed protocol provided an example that analysis of selected component markers could serve for health security and quality control of TCM consumption. PMID- 17723622 TI - Sol-gel monolithic anion-exchange column for capillary electrochromatography. AB - A single-step approach has been used to prepare a monolithic electrochromatographic column by sol-gel processing of an organofunctional silicon alkoxide precursor that contains a propyl-N,N,N-trimethylammonium group. We have found that the time of adding the porogen, poly(ethylene glycol), during the sol-gel reaction affected the separation performance. Since the surface charge of this material is switchable in sign upon manipulation of solution pH, the direction and magnitude of the electroosmotic flow (EOF) can be controlled by adjusting the pH of the running electrolyte. By controlling the direction of the EOF from cathode to anode, inorganic anions can be separated in a short time. Because of the quaternary ammonium functional group, the resulting material is anion exchangeable. Interestingly, the anion-exchange selectivity of inorganic anions on this column changes with solution pH or applied voltage. The column shows excellent run to run reproducibility (R.S.D.<0.4%), good day to day reproducibility (R.S.D.<4%), and reasonable column to column reproducibility (R.S.D.<9%). PMID- 17723623 TI - Simultaneous determination of l-ascorbic acid, ascorbic acid-2-phosphate magnesium salt, and ascorbic acid-6-palmitate in commercial cosmetics by micellar electrokinetic capillary electrophoresis. AB - L-ascorbic acid (LAA) can be used as a whitening agent in cosmetics. Because of its instability, some more stable derivatives have been developed to control melanin production, such as ascorbic acid-2-phosphate magnesium salt (AAPM) and ascorbic acid-6-palmitate (AA6P). To assess the quality of cosmetics, a micellar electrokinetic capillary electrophoresis technique (MEKC) was established for simultaneous analysis of AA and its two derivatives. Separation was performed with 10mM borate (pH 9.5) containing 50 mM sodium dodecyl sulfate (SDS) at 20 kV. The detection wavelength was 265 nm. Several parameters, including borate concentration, buffer pH, and SDS level, were investigated. On method validation, calibration curves were linear over a concentration range of 150.0-1000.0 microM for LAA and 200.0-1000.0 microM for AAPM and AA6P. For intraday and interday analysis, relative standard deviation and relative errors were all less than 3%. Limits of detection were 70 microM for AAPM and AA6P, and 50 microM for LAA. All recoveries were greater than 95%. This method was applied to quality control of commercial cosmetics. PMID- 17723624 TI - Attenuated total reflection Fourier transform infrared spectra of faceted diamonds. AB - Attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy has been employed for characterization of faceted diamonds. ATR spectra of round brilliant cut natural diamonds of approximately 0.1 ct were observed with excellent spectral quality. The mirror-flat spectrum of the table facet enables a good contact to the ATR crystal with a minimal applied pressure. The observed ATR spectra agreed very well with the diffuse reflectance and transflectance spectra. The detailed spectral information in the one-phonon region of diamonds with high nitrogen impurities can be clearly observed in the ATR spectra but those in the diffuse reflectance and transflectance spectra were obscured by the saturated absorption. The strong evanescent field under the ATR condition enables spectral acquisition of a thin film on the mirror-flat surface of the faceted diamonds. The spectral signatures of this thin film were not observable in the diffuse reflectance or the transflectance spectra. PMID- 17723625 TI - Analysis of salicylic acid based on the fluorescence enhancement of the As(III) salicylic acid system. AB - A new, simple and sensitive spectrofluorimetric method for the determination of salicylic acid (lambda(ex)=315 nm, lambda(em) = 408 nm) using As(III) as a sensitizing reagent has been investigated by measuring the increase of fluorescence intensity of salicylic acid due to the complexation of As(III) salicylic acid in presence of sodium dodecyl sulfate (SDS) 10(-3) M. Under optimum conditions, a significant relationship was obtained between the fluorescence intensity and salicylic acid concentration. A linear calibration curve was obtained in the range 13.8-13812 microg l(-1) with product-moment correlation coefficient (R) 0.99985 and detection limit 4.2 microg l(-1). The R.S.D. is 2.35% (n=5). The method was applied successfully to the determination of salicylic acid in human serum. PMID- 17723627 TI - Per-O-methylation reaction for structural analysis of carbohydrates by mass spectrometry. AB - Per-O-methylation of carbohydrates is an important sample preparation step in structural analysis of complex carbohydrates, which has generated considerable interest as shown by thousands of citations in the last 10 years. This article provides a critical overview of the per-O-methylation methods applied for structural analysis of carbohydrates by mass spectrometry. The understanding of the O-methylation mechanism can help the researchers to apply the adequate O methylation method and can generate new ideas in the effort of improving this reaction. The per-O-methylation of carbohydrates is relied upon stepwise reactions. The parameters that affect the reaction are discussed for the most important methods and are critically commented for each reaction step. The limits of each method are emphasized. The improvements of the per-O-methylation reaction are described in detail with their advantages and disadvantages and some illustrative examples are given. The methods that give complete O-methylation in non-hazardous conditions with high yields within minutes at room temperature with a very low amount of side-products are especially highlighted. PMID- 17723626 TI - Distribution characteristics of methamphetamine and amphetamine in urine and hair specimens collected from alleged methamphetamine users in northern Taiwan. AB - This study was conducted to better understand the distribution characteristics of methamphetamine and amphetamine in urine and hair specimens collected from alleged methamphetamine users in the local population. It is anticipated that the data hereby obtained will be helpful to the interpretation of the time and pattern of drug use. Eight alleged methamphetamine-using arrestees from Keelung Police Department (north of Taipei, Taiwan) consented to contribute both urine and hair specimens. Each arrestee contributed seven urine specimens collected at 0, 12, 24, 48, 72, 96, and 120 h, respectively, after the arrest. Hair specimens were cut into 2-cm sections. The limits of detection and quantitation of the urine protocol were 40 and 50 ng/mL, respectively, for both amphetamine and methamphetamine, while the corresponding limits of detection and quantitation for the hair protocol were 0.8 and 1.0 ng/mg, respectively. The concentration variations of methamphetamine and amphetamine in the urine specimens exhibited three distinct patterns: (a) continuous decrease in the analytes' concentrations for specimens collected at hours 0-120; (b) increase in the analytes' concentrations in specimens collected at hours 0-12, followed by decrease; (c) increase in analytes' concentrations in specimens collected at later times. Together with the amphetamine/methamphetamine concentration ratios found in these urine specimens, the observed trends in the changes of the analytes' concentrations are helpful for the interpretation on the time of drug use. Unlike urine specimens, amphetamine/methamphetamine concentration ratios in various hair specimens and hair sections remain relatively constant. PMID- 17723628 TI - Determination of benzene in gasoline using direct injection-mass spectrometry. AB - A high-speed determination of benzene in gasoline samples using a non-separative method based on direct injection into the mass spectrometer is proposed. The results obtained are very similar to those provided with fast GC-MS. The calibration set was made up of gasoline samples in which the benzene was determined chromatographically and samples of gasoline subjected to a process of evaporation--until the complete disappearance of the original benzene--to which known concentrations of this compound had been added. A PLS1 multivariate calibration model was constructed. Cross-validation was used to select the optimum number of PLS components. The prediction capacity of the model was checked with an additional group of gasoline samples that had not been used either in the construction or in the validation of the model. With the direct injection method proposed here it was possible to analyse 24 samples over a period of 1h. The direct injection method is rapid, simple and--in view of the results--highly suitable for the determination of benzene in gasoline samples. PMID- 17723629 TI - Determination of 36 elements in plant reference materials with different Si contents by inductively coupled plasma mass spectrometry: comparison of microwave digestions assisted by three types of digestion mixtures. AB - Closed-vessel microwave digestion of nine standard reference plant materials (NIST, BCR, IAEA) and a laboratory standard of plant material with different Si contents assisted by HNO3 + H2O2 (procedure A), HNO3 + H2O2 + HF + H3BO3 (procedure B) and HNO3 + H2O2 + HBF4 (procedure C) were used to determine the recovery of 36 elements by ICP-MS: Ag, Al, As, Ba, Be, Bi, Cd, Ce, Co, Cr, Cs, Cu, Fe, Ga, Ge, In, La, Li, Mn, Mo, Nd, Ni, Pb, Pr, Rb, Sb, Se, Sn, Sr, Th, Tl, U, V, W, Y, Zn. Additions of HF + H3BO3 and HBF4 in procedures B and C exceeded by 10% (B1, C1) and 100% (B2, C2) the equivalent concentrations of Si in the samples determined by ICP-OES. Most recoveries of certified elements (e.g., Al*, Cu, Mo*, Rb*, Sb*, Th) decreased significantly (*p < or = 0.05) with increasing Si content in plant reference materials digested by procedure A, while the recoveries from procedures B and C decreased insignificantly only for Mo and Sb. Digestions B and C gave significantly higher recoveries of Al, Sb, W and REEs, which were tighter to the reference values of these elements. A similar effect was found for Cu, Fe, Li, Ni, Sn, Th, Tl, V, Zn, Ba, Rb and Sr recoveries in samples with Si contents exceeding 2000 microg g(-1). If the Si content in plant samples is less than 10 mg g(-1), digestion of 0.5 g of plant samples through 0.05 mL of HF and 0.5 mL of 4% H3BO3 or 0.1 mL of HBF4 is recommended to get satisfactory results for most of the elements. For materials with Si content exceeding 10 mg g(-1) the weight of the sample for digestion should be reduced to 0.25 g. However, the operation of potential interferences should be taken into account and eliminated through correction equations and adequate dilution of the samples. PMID- 17723630 TI - A novel route for immobilization of oligonucleotides onto modified silica nanoparticles. AB - A novel approach for immobilization of probe oligonucleotides that uses zirconium phosphate modified silica nanoparticles is proposed. The surface modification of nanoparticles was carried out in two stages. Initially binding of Zr4+ to the surface of silica nanoparticles and later treated with phosphoric acid for terminal phosphate groups. Oligonucleotide probes modified with amine group at 5' end were strongly binds to the phosphate terminated silica nanoparticles with imidazole in presence of 0.1 mol L(-1) EDC [N-ethyl-N'-(3-dimethylaminopropyl) carbodiimide], as phosphate groups are more reactive towards amine group. Various studies, i.e., synthesis of silica nanoparticles, their surface modification, probe immobilization, measurement of hybridization and effect of bovine serum albumin (BSA) were carried out during optimization of reaction conditions. The significant reduction in the background signal was observed by treating the probe modified silica nanoparticles with bovine serum albumin prior to hybridization. The probe modified silica nanoparticles were retained their properties and the hybridization was induced by exposure of single-stranded DNA (ssDNA) containing silica nanoparticles to the complementary DNA in solution. The decrease in the fluorescence signal for one mismatch and three mismatch was observed upon hybridization of probe with target DNAs, while there was no response for the random target ssDNA under the same experimental conditions. The intensity of fluorescence signal was linear to the concentration of target DNA ranging from 3.9 x 10(-9) to 3.0 x 10(-6)mol L(-1). A detection limit of 1.22 x 10(-9) mol L( 1) of oligonucleotides can be estimated. The proposed hybridization assay is simple and possesses good analytical characteristics and it can provide an effective and efficient route in the development of DNA biosensors and biochips. PMID- 17723631 TI - Simultaneous analysis of the photocatalytic degradation of polycyclic aromatic hydrocarbons using three-dimensional excitation-emission matrix fluorescence and parallel factor analysis. AB - Polycyclic aromatic hydrocarbons (PAHs) may be photochemically degraded. Monitoring of degradation process of PAHs is carried out by traditional methods, which normally imply time-consuming procedures that do not allow the chemical process to be analyzed in real time. In the present study, photodegradation kinetics of dibenz[a,h]anthracene, benz[a]anthracene, benz[a]pyrene and benz[k]fluorantene were investigated in aqueous solutions under different conditions. A 2(3) factorial design was used for optimizing the degradation process. Fluorescence spectroscopy is a fast, cheap and sensitive analytical method, attractive for use in conjunction with chemometric methods; in this case three-way analytical methodology based on fluorescence excitation-emission matrix (EEM) and parallel factor analysis (PARAFAC) was employed. A four-factor PARAFAC model made it possible to resolve the species presents in the degradation mixture and quantify the relative concentration of the analytes throughout the degradation. Several different parameters, such as core consistency, percentage of fit and correlation coefficients between recovered and reference spectra were employed to determine the suitable number of factors for the PARAFAC model. This new methodology allows us to determine satisfactorily the PAHs concentration during the photodegradation in mixtures of arbitrary composition, representing an interesting alternative to the conventional techniques normally used for the monitoring of degradation reactions. PMID- 17723632 TI - Investigation on sensitized chemiluminescence systems and their mechanism for five fluoroquinolones. AB - The novel chemiluminescence (CL) reaction systems were established for lomefloxacin (LMFX), ofloxacin(OFLX), norfloxacin (NFLX), gatifloxacin (GAFX) and enoxacin (ENX). The sensitized CL emission mechanism was investigated for the five systems by comparing the fluorescence emission with CL spectra. For LMFX Ce(IV)-S2O3(2-)-H2SO4 and OFLX-Ce(IV)-S2O4(2-)-H2SO4 systems, the CL intensity is enhanced through intermolecular energy transfer from the excited SO2* to LMFX and OFLX. For NFLX-Ce(IV)-S2O4(2-)-HNO3 system, the sensitized CL is based on intermolecular energy transfer from the excited SO2* to NFLX oxide. For Eu3+-GAFX Ce(IV)-S2O4(2-)-HCl and Dy3+-ENX-Ce(IV)-S2O3(2-)-H2SO4 systems, the CL spectra are from the narrow characteristic emission at 590, 619 and 649 nm of Eu3+* (5D0- >7F1, 5D0-->7F2, 5D0-->7F3) and at 482 and 578 nm of Dy3+ (4F9-->6H15/2, 4F9- >6H13/2) through intermolecular energy transfer from the excited SO2* to GAFX and ENX, followed by intramolecular energy transfer from GAFX* to Eu3+ and ENX* to Dy3+. The conditions of CL emission were investigated and optimized. The proposed five enhanced CL systems have good linearity, higher sensitivity, precision and potential capability for residue analysis of studied analytes in foods and biological samples. PMID- 17723633 TI - Leachability and analytical speciation of antimony in coal fly ash. AB - The present study assesses the single extraction of Sb from two coal fly ashes with aqueous solutions at a range of pHs (1-12) and with citrate 1 mol L(-1) at pH 5, in order to obtain preliminary information about Sb leaching from this matrix. Speciation analysis of the coal fly ash extracts by HPLC-ICP-MS and HPLC HG-AFS was carried out in order to identify the presence of individual Sb species. Sb(V) was the main Sb species in the leachates, although minor amounts of Sb(III) were also detected in some extracts. Citrate at pH 5 gave the best extraction efficiency for both samples whereas Sb species were also fairly soluble in aqueous solutions at acidic pHs. Analysis by HPLC-ICP-MS provided the most accurate results in some extracts (aqueous solution at pH 1 and citrate at pH 5) when both coupled techniques used were compared. The presence in these leachates of higher content of interfering metal ions (Ca, Fe and Pb) than those obtained for the Sb species reduced stibine generation in the HPLC-HG-AFS analysis. The proposed methodology can be considered reliable and useful for antimony speciation in environmental studies. PMID- 17723635 TI - Mechanistic aspects of electrochemical hydride generation for cadmium. AB - The mechanistic aspects of a novel methodology for the electrochemical hydride generation (EcHG) of cadmium, entitled as the catholyte variation, have been studied. The hydrogen overvoltage of different cathode materials was determined in dilute electrolyte. The lead-tin alloy used as the cathode material for the EcHG of Cd had the highest hydrogen overpotential. In this technique, both electrolyte medium and cathode surface would change during electrolysis. The catholyte variation EcHG coupled with a flame heated quartz tube atomizer (QTA) atomic absorption spectrometer (AAS) produced peak-shaped transient signal of Cd. The analytical signal was significantly enhanced at neutralization time. The simultaneous production of lead and tin hydrides as well as the hydrogen at that time may speed up the desorption of cadmium species from the surface of the cathode. Also the high hydrogen overvoltage and the neutral medium aided the formation and separation of cadmium hydride molecules. The generated CdH2 vapour was kinetically stable. PMID- 17723636 TI - Comparison of liquid-liquid extraction, solid-phase extraction and co precipitation preconcentration methods for the determination of cadmium, copper, nickel, lead and zinc in seawater. AB - Three major types of pre-concentration methods were evaluated and optimised for the extraction and determination of Cd, Cu, Ni, Pb and Zn from seawater samples. The traditional APDC/DDDC-Freon liquid-liquid extraction method showed excellent results for a multi-elemental analysis. However, the technique is labour consuming, very sensitive to operational conditions, employs environmentally unsafe and expensive solvents and requires large sample volumes. In the solid phase extraction method, the performances of a traditional Amberlite XAD-4 and a novel Dowex Optipore V-493 were evaluated. Application of Dowex Optipore V-493 resin provided better results at low concentrations than the generally used Amberlite XAD-4 resin using low sample volumes. However, the presence of natural organic compounds may decrease extraction efficiency of both resins for Cu. Thus, a pre-treatment with UV irradiation is advantageous for samples with high organic content. Cobalt co-precipitation methods showed good Cu and Ni recoveries, but gave poor results for Cd at low concentrations. In addition, high sample volumes are required. Both solid phase and co-precipitation methods showed unsatisfactory results in determination of Pb. Finally, a summary of methods advantages are given for choosing the most suitable method. PMID- 17723634 TI - On-line cloud point extraction combined with electrothermal vaporization inductively coupled plasma atomic emission spectrometry for the speciation of inorganic antimony in environmental and biological samples. AB - A new method for the determination of inorganic Sb species by on-line cloud point extraction combined with electrothermal vaporization inductively coupled plasma atomic emission spectrometry (ETV-ICP-AES) is presented and evaluated. The method is based on the complexation of Sb(III) with pyrrolidine dithiocarbamate (PDC) which form an hydrophobic complex at pH 5.5 and subsequently enter surfactant rich phase at pH 5.5, whereas Sb(V) remained in aqueous solutions. The preconcentration step is mediated by micelles of the non-ionic surfactant Triton X-114 with ammonium pyrrolidine dithiocarbamate (APDC). The micellar system containing the complex was loaded into the FIA manifold at a flow rate of 2.5 mL min(-1), and the surfactant-rich phase was retained in a microcolumn packed with absorbent cotton, at pH 5.5. After the surfactant-rich phase was eluted with 100 microL acetonitrile, it was determined by ETV-ICP-AES. Sb(V) is reduced to Sb(III) by l-cysteine prior to determined total Sb, and its assay is based on subtracting Sb(III) from total antimony. The main factors affecting separation/preconcentration and the vaporization behavior of analyte in graphite tube were investigated in detail. Under the optimized conditions, the precision relative standard deviation (R.S.D.) for eight replicate measurements of 0.2 microg mL(-1) Sb(III) was 4.3%. The apparent concentration factor, which is defined as the concentration ratio of the analyte in the final diluted surfactant rich extract ready for ETV-ICP-AES detection and in the initial solution, was 872 for Sb(III). The limit of detection (LOD) for Sb(III) was 0.09 microg L(-1). The proposed method was successfully applied for the speciation of inorganic antimony in different water samples and urine sample with satisfactory results. PMID- 17723638 TI - An improved method to detect ethyl glucuronide in urine using reversed-phase liquid chromatography and pulsed electrochemical detection. AB - Pulsed electrochemical detection (PED) following reversed-phase liquid chromatography (LC) has been applied recently to the detection of ethyl glucuronide (EtG) in the urine of live and deceased individuals. In this paper, several key improvements to the method are made to enhance sensitivity, reproducibility, and accuracy. These improvements include (i) further optimization of the sample preparation procedure that has increased the recovery from ca. 50% to 84+/-3% in synthetic urine matrix; (ii) changing the internal standard from methyl glucuronide (MetG) to propyl glucuronide (ProG), which does not elute within the interference of the matrix; and (iii) altering the mobile phase of the separation from acetonitrile to t-butanol to virtually eliminate signal suppression in PED. As a consequence, detection limits have been reduced to 0.01 microg mL(-1), reproducibility has been improved by a factor of two, and sample size has been reduced five-fold. Blind studies in synthetic urine showed no significant difference between the amount recovered and the true value determined at the 95% confidence level for all samples. Importantly, PED requires no derivatization, and it can detect virtually all glucuronides. PMID- 17723637 TI - Heteroscedasticity of retention factor and adequate modeling in micellar liquid chromatography. AB - The two concepts of micelle formation (pseudo-phase and mass-action) could be the basis of retention models in micellar liquid chromatography (MLC). The separation of 4-hydroxybenzoic acid esters and seven polyaromatic hydrocarbons were performed to study the repeatability of retention factor in MLC. The full two factor experimental design was used for studying the dependence of retention factor variance on mobile phase composition (sodium dodecylsulfate, 1-butanol). The experimentally observed heteroscedasticity and perturbations after linearization were taken into account by using statistical weights obtained on the basis of errors propagation law and the modeling of retention by non-weighted and weighted least squares method was performed. The mechanistical retention models based on pseudo-phase and mass-action concepts of micelle formation were compared by fitting quality and prediction capability and high robustness of bilogarithmic dependence was observed. The significance of retention factor heteroscedasticity for retention hydrophobicity relationships was shown. PMID- 17723639 TI - Determination of cefuroxime axetil in tablets and biological fluids using liquid chromatography and flow injection analysis. AB - Cefuroxime axetil is the pro-drug of cephalosporin cefuroxime that is used in the treatment of common community-acquired infections. A simple and precise liquid chromatographic method for the determination of cefuroxime axetil in pharmaceutical tablets, human serum and urine has been developed and validated. Cefuroxime axetil and indapamide (internal standard) were separated by a reversed phase column (Supelco Hypersil 5 microm, 150 mm x 4.6 mm i.d., C18) using a mobile phase consisting of KH2PO4 (0.1 M) and acetonitrile (70:30 v/v) (at pH 4.0). The mobile phase was pumped at 1.0 mL min(-1) flow rate and cefuroxime axetil was detected by ultraviolet detection at 281 nm within an average analysis time of 11 min. Flow injection analysis was performed for pharmaceutical tablet analysis using a carrier stream of methanol:water (10:90v/v) with a flow rate of 1.0 mL min(-1). The LOD and LOQ concentrations of the HPLC method were 1.35 x 10( 7) and 4.08 x 10(-7)M for the HPLC analysis and 1.31 x 10(-7) and 4.00 x 10(-7)M for FIA. The results of the analysis of the tablet formulation obtained by using these methods were statistically comparable with each other and with an additional spectrophotometric method. There was no significant difference between all these methods. PMID- 17723640 TI - Stability indicating high-performance thin-layer chromatographic determination of gatifloxacin as bulk drug and from polymeric nanoparticles. AB - A simple, sensitive, selective, precise and stability indicating high-performance thin-layer chromatographic method for determination of gatifloxacin both as a bulk drug and from polymeric nanoparticles was developed and validated as per the International Conference on Harmonization (ICH) guidelines. The method employed thin-layer chromatography (TLC) aluminium plates precoated with silica gel 60F 254 as the stationary phase and the mobile phase consisted of n-propanol-methanol concentrated ammonia solution (25%) (5:1:0.9, v/v/v). This solvent system was found to give compact spots for gatifloxacin (R(f) value of 0.60+/-0.02). Densitometric analysis of gatifloxacin was carried out in the absorbance mode at 292 nm. The linear regression analysis data for the calibration plots showed good linear relationship with r=0.9953 with respect to peak area in the concentration range of 400-1200 ng spot(-1). The mean value (+/-S.D.) of slope and intercept were 9.66+/-0.05 and 956.33+/-27.67, respectively. The method was validated for precision, accuracy, ruggedness and recovery. The limits of detection and quantitation were 2.73 and 8.27 ng spot(-1), respectively. Gatifloxacin was subjected to acid and alkali hydrolysis, oxidation, photodegradation and dry heat treatment. The drug undergoes degradation under acidic and basic conditions and upon wet and dry heat treatment. The degraded products were well separated from the pure drug. The statistical analysis proves that the developed method for quantification of gatifloxacin as bulk drug and from polymeric nanoparticles is reproducible and selective. As the method could effectively separate the drug from its degradation products, it can be employed as stability-indicating one. PMID- 17723641 TI - Novel catalytic oxidative coupling reaction of N,N-dimethyl-p-phenylenediamine with 1,3-phenylenediamine and its applications to the determination of copper and iron at trace levels by flow injection technique. AB - A new catalytic oxidative coupling reaction of N,N-dimethyl-p-phenylenediamine (DPD) with 1,3-phenylenediamine (mPD) in the presence of hydrogen peroxide has been developed for trace metals analysis. The rate of the oxidation/coupling reaction can be enhanced significantly by iron, copper and cobalt. These metal ions can catalyze the oxidation reaction of DPD to form an oxidized product; the oxidized DPD was then coupled with mPD to give a blue-colored product which was measured spectrophotometrically at 650 nm. On the basis of such a reaction scheme, two simple flow injection analysis methods for the determination of copper and iron have been developed. Detailed studies on chemical and FIA variables affecting the sensitivity of the detection were carried out. Interferences from several ionic species were examined for the determination of copper: the interference effect by Fe(III) and Fe(II) up to 1.5 mg L(-1) was successfully suppressed by pretreating sample with ammonium acetate buffer solution (pH 8.4). Good linearity of a standard calibration graph was obtained over the ranges of 0-8 and 0-2 microg L(-1) of copper and iron, respectively, and the detection limits were 0.05 and 0.02 microg L(-1) for copper and iron, respectively. The precision of the methods in terms of relative standard deviation were 1.4 and 1.5% of R.S.D. which were obtained from 10 injections of 2.0 and 1.0 microg L(-1) of standard copper and iron, respectively. The proposed methods were successfully applied to the determination of copper and iron in tap and river water samples. The accuracy of the proposed methods was assessed by the analysis of certified reference material of river water. PMID- 17723642 TI - Flow-injection methylene blue-based spectrophotometric method for the determination of peroxide values in edible oils. AB - A flow-injection method for measuring the peroxide value (PV, mequiv. O2 kg(-1)) in edible oils is described. The technique is based on spectrophotometric monitoring at 660 nm of methylene blue (MB), generated from leucomethylene blue (LMB) oxidation with peroxides present in oil samples. After being optimized, the method was validated in terms of linearity, precision sensitivity and recovery. Linear calibration graph was obtained in the range 0.1-5 mequiv. O2 kg(-1), with a detection limit (S/N=3) of 0.014 mequiv. O2 kg(-1). The precision of the method (R.S.D., n=9) for within and between-days is better than 1.5% and 2.2%, respectively at 0.4 mequiv. O2 kg(-1). The method was applied successfully to the determination of PV in six edible oil samples, and compared to the classical official method. Using the linear regression test, Student's t-test and variance ratio F-test, there was no significant difference between the compared methods. The proposed method is accurate, simple, cheap and could be used to control edible oil rancidity with a high sample throughputs (30 samples h(-1)). PMID- 17723643 TI - Application of 8-amino-N-(2-hydroxybenzylidene)naphthyl amine as a neutral ionophore in the construction of a lanthanum ion-selective sensor. AB - In this work, a novel La(III) membrane sensor based on 8-amino-N-(2 hydroxybenzylidene)naphthylamine (AIP) is presented. This electrode reveals good selectivity for La(3+) over a wide variety of lanthanides metal ions. Theoretical calculations and conductance study of AIP to lanthanum and some other metal ions were carried out and confirmed selectivity toward La(III) ions. The electrode comprises 7% AIP, 30% PVC, 61% NPOE and 2% KTpClPB. The sensor displays a linear dynamic range between 1.0 x 10(-7) and 1.0 x 10(-1) M, with a nice Nernstian slope of 20.3+/-0.3 mV per decade and a detection limit of 8.0 x 10(-8) M. The potentiometric response is independent of pH in the range of 4.0-9.0. The proposed sensor posses the advantage of short response time, and especially, very good selectivity towards a large number of cations, such as Sm(III), Ce(III, Pr(III), Yb(III) and Hg(II), low detection limit and wide linear dynamic range in comparison with former ones. The electrode can be used for at least seven weeks without any considerable divergence in the potentials. It was used as an indicator electrode in the potentiometric titration of La(III) ions with EDTA. The sensor was applied to the determination of La(III) ions concentration in binary mixtures. It was also applied for the determination of fluoride ions in mouth wash preparations. PMID- 17723644 TI - Polymer-coated bismuth film electrodes for the determination of trace metals by sequential-injection analysis/anodic stripping voltammetry. AB - In this work, the utility of polymer-coated bismuth film electrodes (BiFEs) was assessed for the simultaneous on-line determination of Cd(II), Pb(II) and Zn(II) by square-wave anodic stripping voltammetry (SWASV) in the sequential-injection analysis (SIA) mode. The polymeric Nafion coating was initially plated on a glassy carbon electrode forming part of the flow-through electrochemical cell. The subsequent steps of the bismuth layer generation, analyte preconcentration, voltammetric measurement and electrode cleaning were conducted on-line. For a sample volume of 1.2 mL, the limits of detection (at S/N=3) were 2 microg L(-1) for Cd(II) and Pb(II) and 6 microg L(-1) for Zn(II), the coefficients of variation at 20 microg L(-1) were 5.1% for Cd(II), 5.9% for Pb(II) and 6.2% for Zn(II) and the measurement frequency was between 10 and 20 h(-1) (depending on the sample volume aspirated). It is demonstrated that the polymer-coated BiFEs, combined with SIA, can provide an environmentally friendly, sensitive and robust tool to perform rapid and cost-efficient on-line monitoring of trace metals by ASV, even in the presence of surface-active compounds. PMID- 17723645 TI - Monitoring of the insecticide trichlorfon by phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy. AB - Trichlorfon is an organophosphorus insecticide, which is extensively being used for protection of fruit crops. Trichlorfon is a thermal labile compound, which cannot be easily determined by gas chromatography (GC) and has no suitable group for sensitive detection by high performance liquid chromatography (HPLC). In this study, a 31P nuclear magnetic resonance (31P NMR) has been described for monitoring of trichlorfon without any separation step. The quantitative works of 31P NMR spectroscopy has been performed in the presence of an internal standard (hexamethylphosphoramide). Limit of detection (LOD) for this method has been found to be 55 mg L(-1), without any sample preparation, and the linear working range was 150-5500 mg L(-1). Relative standard deviation (R.S.D.%) of the method for three replicates within and between days was obtained < or =9%. The average recovery efficiency was approximately 99-112%. This method was applied for monitoring trichlorfon in a commercial insecticide sample and tomato sample. PMID- 17723646 TI - Chromatographic separation for domoic acid using a fragment imprinted polymer. AB - We prepared molecularly imprinted polymers for an amnesic shellfish poison, domoic acid. To prepare the polymer, we tested several commercial aromatic dicarboxylic compounds such as isomers of phthalic acid for templates of molecularly imprinted polymers. The highest selective recognition ability of the polymer for domoic acid in the tested compounds was found when o-phthalic acid was used as the template. The ability was due to the acidity of the carboxylic acids in the domoic acid and the similarity of the shape around the carboxylic acids of domoic acid and the templates. The effective chromatographic separation of domoic acid in the extract from blue mussels was achieved with a LC column packed with the fragment imprinted polymer using o-phthalic acid as the template. This polymer can be utilized for a clean up procedure of domoic acid in toxic shellfish. PMID- 17723647 TI - Ultra-performance liquid chromatography-tandem mass spectrometry: a novel challenge in multiresidue pesticide analysis in food. AB - Potential of ultra-performance liquid chromatography (UPLC) separation strategy coupled with tandem (in space) mass spectrometric detection (MS/MS) in multiresidue pesticide analysis was critically assessed. Performance parameters such as number of theoretical plates, height of theoretical plate, peak symmetry and peak capacity were measured/calculated on the basis of data generated by analysis of apple extracts containing 17 (semi)polar pesticides representing various classes of active ingredients of widely used crop protective preparations. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) procedure provided improved chromatographic parameters resulting in significantly increased sample throughput including lower solvent consumption and lower limits of quantitation (LOQs) for most of target analytes compared to common method employing conventional high-performance liquid chromatography (HPLC) separation. PMID- 17723648 TI - Method optimization for the determination of four mercury species by micro-liquid chromatography-inductively coupled plasma mass spectrometry coupling in environmental water samples. AB - A method based on the coupling microHPLC-microneb-ICPMS has been developed for Hg(II), MeHg+, EtHg+ and PhHg+ species. Gradient elution using methanol and l cysteine at pH 3.0 allowed the chromatographic separation of all species in less than 13 min (total analysis time 15 min). The direct coupling of microLC to ICPMS through a Micromist nebulizer permits the analysis of environmental water without sample pretreatment and derivatization steps. Nebulizer type, organic modifier and column length were the main parameters tested. The methanol content and pH of the mobile phase greatly affected the retention time and sensitivity of the method. Key factors to obtain high signal to noise ratio, at concentrations below 1 microg L(-1), were found to be the nebulization step and traces of Hg present in the complexing agent. A detailed optimization of carrier and make up gas flow rates have enabled the nebulization of the methanol gradient elution with good mass transport efficiency, low organic solvent loading into the plasma and excellent precision. The performance of the microHPLC-microneb-ICPMS method developed was evaluated on a surface water sample filtered (0.22 microm) and spiked with 0.5 microg L(-1) (as Hg) of each species. Precision (R.S.D., n=6) for all species of Hg varied from 0.5 to 2.1%. Detection limit, defined as three times the standard deviation (n=6), ranged from 8 ng L(-1) for EtHg+ to 32 ng L( 1) for PhHg+ and was noticeably lower than those reported in previous LC-based methods. Accuracy was suitable with recoveries ranging from 85 to 100% when tested at two levels (0.5 and 10 microg L(-1)) in groundwater samples. Recovery was matrix affected when water samples of high salinity (depurated wastewater and seawater) were used. PMID- 17723649 TI - Simultaneous determination of naphthoquinone derivatives in Boraginaceous herbs by high-performance liquid chromatography. AB - A high-performance liquid chromatographic method using diode-array detection (HPLC-DAD) has been developed for the simultaneous quantification of eight naphthoquinone derivatives namely shikonin, acetylshikonin, deoxyshikonin, beta acetoxyisovalerylshikonin, isobutylshikonin, beta,beta-dimethylacrylshikonin, 2 methyl-n-butyrylshikonin and isovalerylshikonin in nine species of the Boraginaceae family. These species, coming from different areas of China, are all used as interchangeable sourcing plants for the Chinese Materia Medica known as "Zicao", and are Arnebia euchroma (Royle) Johnston., A. guttata Bunge, Lithospermum erythrorhizon Sieb. et Zucc., Onosma paniculatum Bur. et Franch., O. exsertum Hemsl., O. confertum W.W. Smith, O. hookerii Clarke var. longiflorum Duthie, O. hookerii Clarke and O. waltonii Duthic. Quantification of the eight naphthoquinones in all the Zicao samples are reported and compared with each other. Furthermore, two positional isomers, 2-methyl-n-butyrylshikonin and isovalerylshikonin, were successfully separated and quantified for the first time in the present study. The results showed that, besides the three officially used species (namely, A. euchroma, A. guttata and L. erythrorhizon) that were listed in Chinese pharmacopoeia as interchangeable sourcing plants for Zicao, other six species of Onosma used by native peoples in Tibet and Yunnan Province also contain various types and considerable amounts of naphthoquinones and that O. waltonii contains the most. Therefore, these species of Onosma could be developed as new sources of naphthoquinones. The entire analytical procedure is reproducible and suitable for the quantification of naphthoquinones in all related Boraginaceous plants for quality assessment purposes. PMID- 17723650 TI - Low pressure ion chromatography with a low cost paired emitter-detector diode based detector for the determination of alkaline earth metals in water samples. AB - The use of a low pressure ion chromatograph based upon short (25 mm x 4.6 mm) surfactant coated monolithic columns and a low cost paired emitter-detector diode (PEDD) based detector, for the determination of alkaline earth metals in aqueous matrices is presented. The system was applied to the separation of magnesium, calcium, strontium and barium in less than 7min using a 0.15M KCl mobile phase at pH 3, with post-column reaction detection at 570 nm using o-cresolphthalein complexone. A comparison of the performance of the PEDD detector with a standard laboratory absorbance detector is shown, with limits of detection for magnesium and calcium using the low cost PEDD detector equal to 0.16 and 0.23 mg L(-1), respectively. Finally, the developed system was used for the determination of calcium and magnesium in a commercial spring water sample. PMID- 17723651 TI - Approach for ochratoxin A fast screening in spices using clean-up tandem immunoassay columns with confirmation by high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). AB - An approach for ochratoxin A (OTA) fast cost-effective screening based on clean up tandem immunoassay columns was developed and optimized for OTA detection with a cut-off level of 10 microg kg(-1) in spices. Two procedures were tested and applied for OTA detection. Column with bottom detection immunolayer was optimized for OTA determination in Capsicum ssp. spices. A modified clean-up tandem immunoassay procedure with top detection immunolayer was successfully applied for all tested spices. Its main advantages were decreasing of the number of analysis steps and quantity of antibody and also minimizing of matrix effects. The total duration of the extraction and analysis was about 40 min for six samples. Chilli, red pepper, pili-pili, cayenne, paprika, nutmeg, ginger, white pepper and black pepper samples were analyzed for OTA contamination by the proposed clean-up tandem immunoassay procedures. Clean-up tandem immunoassay results were confirmed by HPLC-MS/MS with immunoaffinity column clean-up. Among 17 tested Capsicum ssp. spices, 6 samples (35%) contained OTA in a concentration exceeding the 10 microg kg(-1) limit discussed by the European Commission. All tested nutmeg (n=8), ginger (n=5), white pepper (n=7) and black pepper (n=6) samples did not contain OTA above this action level. PMID- 17723652 TI - Validated high-performance thin-layer chromatography method for determination of trigonelline in herbal extract and pharmaceutical dosage form. AB - A new, simple, sensitive, selective, precise and robust high-performance thin layer chromatographic (HPTLC) method for analysis of trigonelline was developed and validated for the determination of trigonelline in herbal extracts and in pharmaceutical dosage forms. Analysis of trigonelline was performed on TLC aluminium plates pre-coated with silica gel 60F-254 as the stationary phase. Linear ascending development was carried out in twin trough glass chamber saturated with mobile phase consisting of n-propanol-methanol-water (4:1:4, v/v/v) at room temperature (25+/-2 degrees C). Camag TLC scanner III was used for spectrodensitometric scanning and analysis in absorbance mode at 269 nm. The system was found to give compact spots for trigonelline (R(f) value of 0.46+/ 0.02). The linear regression analysis data for the calibration plots showed good linear relationship with r2=0.9991+/-0.0002 in the concentration range 100-1200 ng spot(-1) with respect to peak area. According to the International Conference on Harmonization (ICH) guidelines the method was validated for precision, recovery, robustness and ruggedness. The limits of detection and quantification were determined. The trigonelline content of herbal extracts quantified and estimated from the formulation was found to be well within limits (+/-5% of the labeled content of the formulations). Statistical analysis of the data showed that the method is reproducible and selective for the estimation of trigonelline. PMID- 17723653 TI - Optimisation of derivatisation for the analysis of estrogenic compounds in water by solid-phase extraction gas chromatography-mass spectrometry. AB - An optimisation of derivatisation methods for the simultaneous determination of endocrine disrupting chemicals (EDCs) in water by solid-phase extraction (SPE) gas chromatography-mass spectrometry (GC-MS) was developed in this study. Seven highly potent EDCs including 17beta-estradiol (E2), estrone (E1), 16alpha hydroxyestrone, 17alpha-ethynylestradiol (EE2), bisphenol A, 4-nonylphenol and 4 tert-octylphenol were selected as the target compounds. The SPE technique, followed by the derivatisation with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) was used for the extraction recoveries of compounds from water and effluent samples. The stability of the silylation derivatives under different reaction conditions was investigated. The combined use of BSTFA and pyridine as derivatisation reagents, together with the use of hexane as the final solvent, was preferred in order to generate more stable derivatives of EDCs. The relative response factor (RRF) of all derivatives except that of EE2 was stable 120 h after derivatisation. The addition of pyridine as derivatisation reagent with BSTFA can prevent the conversion of EE2 to other products during the reaction. Several parameters that may affect the recovery of EDCs, such as the SPE flow rate, and water properties including aquatic colloid content and surfactant concentration were tested. The results showed that the flow rate (1-25 mL min( 1)), colloid concentration (0-50 mg L(-1)) and surfactants concentration (0-10 microg L(-1)) did not cause significant decrease in the EDCs recovery. PMID- 17723654 TI - Simultaneous determination of preservatives in soft drinks, yogurts and sauces by a novel solid-phase extraction element and thermal desorption-gas chromatography. AB - A novel solid-phase extraction element combined with thermal desorption-gas chromatography (TD-GC) using a pyrolysis-GC system was applied for the determination of the five preservatives - benzoic acid, sorbic acid, and methyl, ethyl and propyl esters of p-hydroxybenzoic acid - in soft drinks, yogurts and sauces. The extraction element is made of a titanium (Ti) tubing (30 mm x 1.2 mm i.d.x1.6 mm o.d.) coated with a chemically bonded layer of polydimethylsiloxane (PDMS) to a thickness of 500 microm. A sample pH of 2.0, sample volume of 5 ml, extraction time of 45 min with addition of salt (15% m/v NaCl) and TD temperature from 40 to 280 degrees C at a heating rate of 40 degrees Cmin(-1) and maintained at 280 degrees C for 9 min, were selected as optimum extraction and desorption conditions. The linearity of the method was satisfactory over a concentration range of 2-1000 mg L(-1) for benzoic acid and sorbic acid, 0.2-300 mg L(-1) for methyl ester of p-hydroxybenzoic acid, and 0.02-300 mg L(-1) for ethyl and propyl esters of p-hydroxybenzoic acid, and the correlation coefficients were higher than 0.997. The limit of detection ranged from 0.002 to 0.2 mg L(-1). The potential of the proposed method was assessed by applying it to the determination of preservatives in real samples. The recoveries (92-106%) and precisions (R.S.D.s of 0.9-4.6% (n=5)) of the method were examined by analyzing soft drink, yogurt and sauce samples spiked at levels of between 20 and 100 mg L(-1). This simple, accurate and highly sensitive method may be used in the determination of the preservatives in various water-based food samples. PMID- 17723655 TI - Evaluation of the electrophoretic behaviour of opioid peptides Separation by capillary electrophoresis-electrospray ionization mass spectrometry. AB - A general equation established in a previous study was used to model the electrophoretic mobility of a series of opioid peptides as a function of pH of the separation electrolyte. The concordance between the predicted and the experimental electrophoretic mobilities was excellent and the optimum pH for the separation of the modelled compounds could be predicted from a limited amount of experimental data. The equations were also useful for the accurate determination of the ionization constants of the polyprotic analytes. It was also demonstrated that if ionization constant values are known, the CE separations of the studied peptides can easily be predicted taking into account the classical semiempirical relationships between electrophoretic mobility and charge-to-mass ratio (m(e) versus q/M(alpha)). The separations simulated considering the accurate charge-to mass ratios of each peptide at a certain pH value were in good agreement with the experimental results. Once an optimum separation pH value and a running buffer compatible with electrospray mass spectrometry (ESI) detection were selected, a method for the separation and characterization of this series of analytes by capillary electrophoresis-electrospray ionization mass spectrometry (CE-ESI-MS) was established using a commercial sheath-flow interface. Method validation was performed in order to prove the suitability of the proposed method for quantitative analysis. Thus, quality parameters, such as repeatability, reproducibility, limits of detection and linearity were determined. PMID- 17723656 TI - A novel fluorescent array for mercury (II) ion in aqueous solution with functionalized cadmium selenide nanoclusters. AB - Mono-disperse CdSe nanoclusters have been prepared facilely and functionalized with l-cysteine through two steps by using safe and low cost substances. They are water-soluble and biocompatible. Especially these functionalized quantum dots can be stably soluble in water more than for 30 days, and the intensity of fluorescence and absorbance was decreased less than 15% of fresh prepared CdSe colloids. These functionalized CdSe QDs exhibited strong specific affinity for mercury (II) through QDs interface functional groups. Based on the quenching of fluorescence signals of functionalized CdSe QDs at 530 nm and no obvious wavelength shift or no new emission band in present of Hg (II) at pH 7.75 of phosphate buffer solution, a simple, rapid and specific array for Hg (II) was proposed. In comparison with conventional organic fluorophores, these nanoparticles are brighter, more stable against photobleaching, and do not suffer from blinking. Under optimum conditions, the response of linearly proportional to the concentration of Hg (II) between 0 and 2.0 x10(-6) mol L(-1), and the limit of detection is 6.0 x 10(-9) mol L(-1). The relative standard deviation of six replicate measurements is 1.8% for 1.0 x 10(-7) mol L(-1) Hg (II). The mechanism of reaction is also discussed. The proposed method was successfully applied for Hg (II) detection in four real samples with a satisfactory result that was obtained by cold vapor atomic fluorescence spectrometry (CV-AFS). PMID- 17723657 TI - Sulfonated poly(ether ether ketone) as an alternative charged material to poly(vinyl chloride) in the design of ion-selective electrodes. AB - To date, poly(vinyl chloride) (PVC) is the most used polymer in the design of ion selective electrode (ISE) membranes. This paper is focused on the use of sulfonated poly(ether ether ketone) (SPEEK) as an alternative material to PVC for the design of ISEs. SPEEK of the desired degree of sulfonation is synthesized from poly(ether ether ketone) (PEEK). An NH4+-ISE has been chosen as a model electrode to study the efficiency of SPEEK as polymer matrix of the membrane. The material was evaluated in ionophore free ion exchanger membranes as well as in ion-selective electrodes membranes containing nonactine as ionophore. Analytical performance parameters of the prepared electrodes were evaluated. The electrodes show a slope between 50 and 60 mVdec(-1) depending on both the calibration medium and the membrane composition. A linear range of response between 10(-4) and 1.0 M and a lifetime of 1-2 months were obtained. The interferences of cations such us Ca2+, Na+, Li+ and K+ over the prepared ISEs are studied as well. Although the plasticizer in the SPEEK based membrane matrix is not necessary, its presence improves the sensibility. This makes SPEEK a good potential choice over alternative membrane matrices reported in the literature and a promising platform for the establishment of membrane components. PMID- 17723658 TI - Organotin compounds: an ionophore system for fluoride ion recognition. AB - Ion-selective properties were established for membrane electrodes prepared by using organotin compounds of type (L(CN)RSnF2)n, (R=n-Bu (I),=Ph (II)) and (L(CN)SnF3)n (III) (L(CN)=C(6)H4(CH2NMe2)-2). Electrodes formulated with the optimized membranes containing the organotin compounds I-III as ionophores and sodium tetraphenylborate (10-30%) exhibited high selectivity for fluoride over other anions. An electrode prepared with ionophore II using dibutyl phthalate as the plasticizer and 15% sodium tetraphenylborate (NaTPB) as anion additive, possesses the best potentiometric response characteristics. It shows a detection limit of 7.9 x 10(-7) M with a slope of 62.7 mV decade(-1) of activity in buffer solutions of pH 5.5. The interference from other anions is suppressed under this optimized measurement conditions. An entirely non-Hofmeister selectivity sequence (F->CH3COO->Cl->I- approximately Br->ClO4->NO2->NO3->SCN-) with remarkable preference towards fluoride is obtained. The influence on the electrode performances by anion additive was studied, and the possible response mechanism was investigated by UV-vis spectra. The electrode has been used for direct determination of fluoride in drinking mineral water with satisfactory results. PMID- 17723659 TI - Electrodeposited glucose oxidase/anionic clay for glucose biosensors design. AB - An amperometric glucose biosensor was developed using an anionic clay matrix (layered double hydroxide (LDH), Ni/Al-NO3) for the immobilization of glucose oxidase (GOx). The biofilm was prepared by electrodeposition of the clay and GOx and subsequent cross-linking with glutaraldeyde. The Pt surface modified with the Ni/Al-NO3 shows a much reduced noise, giving rise to a better signal to noise ratio for the currents relative to H2O2 oxidation, and a linear range for H2O2 determination wider than the one observed for bare Pt electrodes. Under the optimised operative conditions, the performances of the biosensor have been evaluated by measuring the steady-state currents (at +0.45 V versus SCE) to increasing concentrations of glucose in "air saturated" 0.1 M phosphate buffer (pH 7.0). Both batch and flow injection modes were explored. The response to glucose was linear up to 8.0 and 12.0 mM, and the sensitivities were 7.7+/-0.1 and 19.1+/-0.2 mA M(-1) cm(-2), respectively. The current response of the biosensors does not significantly change for 15 consecutive days in batch and for 10 days in flow, at least, if stored at 4 degrees C in phosphate buffer, when not in use. The effects of interferants and applicability to fruit juices and soft drinks analysis of the biosensor were also investigated. PMID- 17723660 TI - Flow injection chemiluminescence determination of naproxen based on KMnO4-Na2SO3 reaction in neutral aqueous medium. AB - A simple, rapid and sensitive flow injection chemiluminescence (CL) method is described for the determination of naproxen. It was found that strong CL signal was generated when naproxen was mixed with KMnO4 and Na2SO3 in neutral aqueous medium. Under the optimum experimental conditions, the CL intensity was linearly related to the concentration of naproxen from 4.0 x 10(-9) to 1.0 x 10(-6)g mL( 1) (r=0.9993). The detection limit was 2 x 10(-9)g mL(-1) naproxen, the relative standard deviation for 1.0 x 10(-7) g mL(-1) naproxen solution was 1.5% (n=11) and the sampling frequency was 120 h(-1). The method was applied to the determination of naproxen in pharmaceutical preparation with satisfactory results. The mechanism of CL reaction was discussed briefly. PMID- 17723662 TI - Development of an ultrasound-assisted extraction method for biomonitoring of vanadium and nickel in the coastal environment under the influence of the Prestige fuel spill (North east Atlantic Ocean). AB - As a consequence of the Prestige shipwreck occurred in the Northeast Atlantic Ocean in November 2002, the need for establishing the environmental impact caused by metals has been of primary concern. Among the different metals contained in the fuel spill, V and Ni are particularly of interest since they appear at relatively high concentration in the original fuel. Biomonitoring of V and Ni using wild mussels (Mytilus edulis) collected along the Galician Coast (NW Iberian Peninsula) has been performed. Ultrasound-assisted extraction of V and Ni from dried mussel tissues using probe sonication allowed a fast solid-liquid extraction thus facilitating sample preparation from large sample batches used for biomonitoring. V and Ni were determined in shellfish caught in the Galician littoral and tar balls from the Prestige spill by electrothermal-atomic absorption spectrometry and inductively coupled plasma-optical emission spectrometry, respectively. A Plackett-Burman saturated design was applied for screening optimization of variables influencing the ultrasound-assisted extraction of V and Ni from shellfish. Efficient extraction of both metals was obtained from slurries prepared in 2 mL capacity sample vials (10 mg sample with a particle size less than 100 microm) using a 3% (v/v) HNO3 diluent and subjected to probe sonication (3 min; 30% vibrational amplitude of the probe). The method was successfully validated by means of three certified reference materials: NRCC TORT-2 Lobster hepatopancreas, NIST-SRM 1566b Oyster tissue and NIST-SRM 2977 Mussel tissue. The detection limit (LOD) of V and Ni in the marine biological tissues, calculated according to the 3sigma criterion, were 0.24 microg g(-1) and 0.15 microg g(-1) for V and Ni, respectively. V and Ni concentrations in M. edulis were in the range 1.7-4.8 and 0.8-2.8 microg g(-1), respectively. Whilst no significant variations in Ni contents were observed in regard to reference values, an important increase in V concentration is observed at some sampling points, thereby indicating bioaccumulation. PMID- 17723661 TI - A novel approach for the rapid decomposition of Actinide resin and its application to measurement of uranium and plutonium in natural waters. AB - A rapid and robust procedure is described for the decomposition of Actinide resin permitting the routine application of this resin as a preconcentrator. Although the classical Fe(OH)3 precipitation is effective in scavenging actinides, the need for careful handling to recover the sticky precipitate makes the new method much more attractive. The known difficulty of decomposing Actinide resin, which is required prior to the subsequent separation of adsorbed actinides, is innovatively overcome by using a borate fusion attack. This procedure effectively solves the normally encountered problem by safely and speedily decomposing the resin in minutes rather than hours. The alternative and apparently simpler technique of direct ashing of the Actinide resin is not used since it leads to a residue that is not readily leachable. The new technique has been incorporated into a procedure for the isolation of Pu and U from natural water samples and their subsequent quantification by alpha spectrometry. The efficiency of loading of the elements onto Actinide resin has been tested using both batch and column based approaches. The integrated method involving Actinide resin preconcentration, borate fusion, anion and UTEVA chromatography and electrodeposition provides limits of detection of 0.001 BqL(-1) and chemical recoveries in excess of 80% from groundwater and seawater samples as large as 5L. Comparative data, presented for the analysis of independently analysed river, borehole and surface run-off waters using both the described procedure and other competing techniques, show very good agreement. PMID- 17723663 TI - Extraction and determination of elemental selenium in sediments--a comparative study. AB - This paper proposes a new technique to extract elemental Se from soil and sediment samples. In this study, we have identified that the purchased red elemental selenium standard (PF-Se) was impure and rather consisted of a mixture of CS2 soluble amorphous elemental Se (ca. 10%, w/w), water soluble oxidized Se (ca. 15-17%, w/w) and, CS2 insoluble red monoclinic elemental Se. In more recent studies, a slow oxidation and a mineral phase transition of this sample was also observed. The solubility of the amorphous elemental Se in CS2 was at least 0.64 mg L(-1). The black elemental Se purchased from Sigma-Aldrich had a much lower solubility in CS2 (7.2 microg mL(-1)) compared to that given in the literature. Any selenium compounds with electrical charge and polar nature is insoluble in CS2. In a sodium sulphite solution, PF-Se was completely dissolved thus giving a clear indication of the lack of selectivity in that extraction system. Other comparative studies also demonstrated that over extraction did occur with the Na2SO3 method. Compared to Na2SO3, CS2 extraction of elemental Se is not only much simpler, straightforward and with higher analytical precision, but also much more selective and accurate. With HG-AFS, the detection limit can reach as low as 1.0 ng g(-1) in sediment sample owing to a low reagent blank of CS2 solvent. PMID- 17723664 TI - Flow injection system for potentiometric determination of alkaline phosphatase inhibitors. AB - A simple flow injection system for potentiometric detection of alkaline phosphatase (ALP) activity has been developed and adapted for determination of selected inhibitors of this enzyme. In this system monofluorophosphate (MFP) has been applied as a specific ALP substrate. The use of this substrate enables application of fluoride ion selective electrode (FISE) as a detector of the product of the enzyme catalyzed reaction. Moreover, chemical stability and low cost of MFP enables the use of the substrate as a component of the carrier. This way, fluoride ions contained in this substrate define and stabilize baseline signal generated by the detector. Effects from several potential ALP inhibitors and interfering species were studied and discussed. The system allows inhibitive detection of beryllium and vanadate ions at ppb levels with relatively high selectivity, short time of analysis and high throughput of the system (near 8 samples h(-1)). PMID- 17723665 TI - Elucidation of molecular and elementary composition of organic and inorganic substances involved in 19th century wax sculptures using an integrated analytical approach. AB - Wax sculptures contain several materials from both organic and inorganic nature. These works of art are particularly fragile. Determining their chemical composition is thus of prime importance for their preservation. The identification of the recipes of waxy pastes used through time also provides valuable information in the field of art history. The aim of the present research was to develop a convenient analytical strategy, as non-invasive as possible, that allows to identify the wide range of materials involved in wax sculptures. A multi-step analytical methodology, based on the use of complementary techniques, either non- or micro-destructive, was elaborated. X-ray fluorescence and micro Raman spectroscopy were used in a non-invasive way to identify inorganic pigments, opacifiers and extenders. The combination of structural and separative techniques, namely infrared spectroscopy, direct inlet electron ionisation mass spectrometry and high temperature gas chromatography, was shown to be appropriate for unravelling the precise composition of the organic substances. A micro chemical test was also performed for the detection of starch. From this study it has been possible to elucidate the composition of the waxy pastes used by three different sculptors at the end of the 19th century. Complex and elaborated recipes, in which a large range of natural substances were combined, were highlighted. PMID- 17723667 TI - Real-time observation of temperature-dependent protein-protein interactions using real-time dual-color detection system. AB - This study examined the ability of a real-time dual-color detection system to allow direct observations of the kinetics of temperature-dependent protein protein interaction at a single-molecule level. The primary target protein was an Alexa Fluor 488-labeled actin conjugate, which had been pre-incubated with an unlabeled rabbit anti-actin antibody (IgG). The complementary fluorescent protein was Alexa Fluor 633-labeled goat anti-rabbit IgG antibody, which interacts with the rabbit anti-actin antibody (IgG) bound to the Alexa Fluor 488-labeled actin conjugate. The individual protein molecules labeled with different fluorescent dyes in solution were effectively focused, interacted with the other protein molecules at 500 aM, and detected directly in real-time using the dual-wavelength (lambda(ex)=488 and 635 nm) laser-induced fluorescence detection system. The kinetics of the protein-protein interactions were examined at different temperatures (12-32 degrees C). At concentrations in the aM range, the number of bound complex molecules through the protein-protein interaction decreased gradually with time at a given temperature, and increased with decreasing temperature at a set time. A high concentration (above 500 pM) of the protein sample caused aggregation and nonspecific binding of the protein molecules, even though the protein molecules were not an example of complementary binding. The results demonstrated that the real-time kinetics of a protein-protein interaction could be analyzed effectively at the single-molecule level without any time delay using the real-time dual-color detection system. PMID- 17723666 TI - Development of enzyme-linked immunosorbent assays for the detection of deacetoxycephalosporin C and isopenicillin N synthase activity. AB - Although there are a number of existing assays for monitoring the activity of both isopenicillin N synthase (IPNS) and deacetoxycephalosporin C synthase (DAOCS), none have demonstrated the qualities required for screening a mutant library. Hence, enzyme-linked immunosorbent assays (ELISAs) for IPNS and DAOCS were developed based on the detection of the catalytic turnover products isopenicillin N and cephalexin/phenylacetyl-7-aminodeacetoxycephalosporanic acid (G-7-ADCA), respectively. These assays are relatively fast compared to existing assays, such as the hole-plate bioassay, and are amenable with high-throughput screening. Both the IPNS and DAOCS-ELISAs were optimised for use with crude protein extracts rather than purified protein, thereby eliminating any additional time required for purification. The ELISA developed for the detection of cephalexin had an IC50 value of 154+/-9 ng mL(-1) and LOD of 7.2+/-2.2 ng mL(-1) under conditions required for the assay. Good recoveries and correlation was observed for spiked samples when the concentration of crude protein was kept below 1 mg mL(-1). The DAOCS-ELISA was found to have increased sensitivity compared to the hole-plate bioassay (10.3 microg mL(-1)). The IPNS-ELISA did not significantly increase the sensitivity (approximately 5 microg mL(-1)) compared to that of the hole-plate bioassay (16 microg mL(-1)) for isopenicillin N. The minimum amount of crude protein extract required for producing detectable amounts of product for both assays was below 0.5% of the maximum amount of protein that the assay could contain without any effect on the ELISA. This suggests that when screening a mutant library, mutants producing low amounts of the product could still be detected using these assays. PMID- 17723668 TI - A microfluidic protease activity assay based on the detection of fluorescence polarization. AB - This article describes a fluorescence polarization (FP)-based protease assay on a microfluidic device that is compatible with fast and reproducible analyses of protease activities. The optical systems were arranged for simultaneously measuring fluorescence intensities of vertical and horizontal polarization planes, and the binding of tetramethylrhodamine (TMR) labeled-biotin with streptavidin was utilized for optimizing FP detection in continuously flowing solutions within 74-microm wide, 12-microm deep microchannels of a glass chip. In developing off-chip FP-based assays for proteinase K, trypsin, papain and elastase, TMR conjugated-casein protein (TMR-alpha-casein) was employed as a universal substrate. After optimization of the hydrodynamic flow control to allow complete mixing of TMR-alpha-casein and short proteolysis time as possible, and of buffer composition to minimize protein sticking problems, the developed assay was transferred to the microfluidic chip by monitoring FP changes of TMR-alpha casein in the main microchannel. The results indicate that the proposed device would serve as an integrated microfluidic platform with automated injection of reacting species, diffusion-controlled mixing, reaction and detection for protease activities without the need to separate the products. PMID- 17723669 TI - Square wave anodic stripping voltammetric determination of Pb2+ using acetylene black paste electrode based on the inducing adsorption ability of I-. AB - Herein, a sensitive and simplified electrochemical method was proposed for the determination of trace levels of Pb2+ by anodic stripping voltammetry (ASV) based on the inducing adsorption ability of I- toward Pb2+. In the presence of low concentration of I-, Pb2+ was induced to accumulate onto the acetylene black (AB) paste electrode surface, and then reduced at -0.90 V. During the following square wave sweep from -0.90 to -0.30 V, the reduced Pb was oxidized, resulting in a sensitive and well-shaped stripping peak at -0.56 V. Further studies indicate that low concentration of I- significantly enhances the sensitivity of determination of Pb2+. After all the experimental parameters were optimized, a novel and sensitive method was developed for the electrochemical determination of Pb2+. The linear range is found to be from 2.0 x 10(-8) to 4.0 x 10(-6) mol L( 1), and the lowest detectable concentration is estimated to be 6.0 x 10(-9)mol L( 1). This newly proposed method was finally demonstrated with water samples. Otherwise, the anodic stripping responses of Pb2+ on AB paste electrode and graphite paste electrode were compared. PMID- 17723670 TI - Analytical applications of a carbon nanotubes composite modified with copper microparticles as detector in flow systems. AB - In this work we report on the successful use of a composite prepared by dispersion of multi-wall carbon nanotubes (1-5 microm length, 20-50 nm diameter) and copper microparticles within mineral oil as detector for amino acids quantification in flow injection analysis and capillary electrophoresis. The resulting electrode displays a highly sensitive amperometric detection of amino acids, based on the copper dissolution facilitated by the strong activity of amino acids as ligands of Cu(II). The sensor makes possible the detection of amino acids, electroactive or not, at very low potentials (0.000 V) and physiological pH. A correlation between the sensitivity for the amino acids and the amount of copper within the composite is observed, demonstrating the importance of the metal in the sensor response. The best analytical performance is obtained for the electrode containing 12.0% (w/w) copper. The excellent results obtained with the carbon nanotube paste electrodes containing copper (CNTPE-Cu) as detector in flow systems makes them an interesting alternative for further analytical applications involving different bioanalytes. PMID- 17723672 TI - Simple and sensitive liquid chromatographic method with fluorimetric detection for the analysis of gamma-amino-n-butyric acid in human urine. AB - A simple and sensitive liquid chromatographic method is described for the analysis of gamma-amino-n-butyric acid (GABA) in human urine. GABA is increased in the urine of cancer patients and could be used as a biomarker in the diagnosis and treatment of related patients. The method is based on derivatizing GABA with a fluorescent reagent (naproxen acyl chloride) for transforming the non chromophoric GABA to a derivative with chromophoric and fluorophoric properties. The resulting derivative is highly responsive to a fluorimetric detector (lambda(ex)=230 nm, lambda(em)=350 nm). The lower quantitation of the method is attainable at 100 nM GABA with a detection limit about 10nM (S/N=3 with 20 microL injected). Application of the method to the analysis of GABA in the urine of patients with ovarian and uterine cancer was demonstrated. PMID- 17723671 TI - Screening and identification of multi-component in Qingkailing injection using combination of liquid chromatography/time-of-flight mass spectrometry and liquid chromatography/ion trap mass spectrometry. AB - An approach for screening and identification of multi-component in complex traditional Chinese medicine systems with a combinative LC/MS (MS(n)) technique was described in this paper. The chemical profile of Qingkailing injection, a well-known traditional Chinese formula in China, was studied using the established method as for an application. Benefit from combining the accurate mass measurement of LC/TOF-MS to generate elemental compositions and the complementary multilevel structural information provided by LC/ion trap MS(n), 33 components in Qingkailing injection were identified in all. The three isomers of chlorogenic acid, isochlorogenic acid and neochlorogenic acid which are derived from Flos Lonicerae, one of the medicinal materials in Qingkailing, were differentiated by verifying their MS3 fragmentation data. All the components identified were surveyed and classified according to their medicinal materials derivation. This study is expected to provide an effective and reliable pattern for comprehensive and systematic characterization of the complex traditional Chinese medicine systems. PMID- 17723673 TI - Determination of isatin and monoamine neurotransmitters in rat brain with liquid chromatography using palladium hexacyanoferrate modified electrode. AB - The fabrication and application of a novel electrochemical detector (ED) with palladium hexacyanoferrate (PdHCF) chemically modified electrode (CME) for liquid chromatography (LC) were described. The electrochemical behaviors of isatin, monoamine neurotransmitters and their metabolites at this CME were investigated by cyclic voltammetry. It was found that the CME exhibited efficiently electrocatalytic of isatin and showed high sensitivity and stability for determination of monoamine neurotransmitters. The linear ranges were over three orders of magnitude and the detection limits were 2.5 x 10(-8) mol L(-1) for isatin, 2.5 x 10(-10) mol L(-1) for norepinephrine (NE), 2.5 x 10(-10) mol L(-1) for 5-hydroxyindoleacetic acid (5-HIAA), 5.0 x 10(-10) mol L(-1) for dopamine (DA), 1.0 x 10(-9)mol L(-1) for 3,4-dihydroxyphenylacetic acid (DOPAC), 1.2 x 10( 10) mol L(-1) for 5-hydroxytryptamine (5-HT) and 2.5 x 10(-9)mol L(-1) for homovanillic acid (HVA). Combined with microdialysis, the method was successfully applied to study the effect of isatin on the levels of monoamine neurotransmitters in experimental Parkinsonian rats. The results showed that isatin could significantly increase striatal monoamine neurotransmitters release to the basal level. PMID- 17723674 TI - Determination of atrazine and simazine in water samples by high-performance liquid chromatography after preconcentration with heat-treated diatomaceous earth. AB - A sensitive and selective column adsorption method is proposed for the preconcentration and determination of atrazine and simazine. Atrazine and simazine were preconcentrated on heat-treated diatomaceous earth as an adsorbent and then determined by high-performance liquid chromatography (HPLC). Several parameters on the recoveries of the analytes were investigated. The experimental results showed that it was possible to obtain quantitative analysis when the solution pH was 2 using 100 mL of validation solution containing 1.5 microg of triazines and 5 mL of ethanol as an eluent. Recoveries of atrazine and simazine were 95.7+/-4.2% and 75.0+/-1.9% with a relative standard deviation for seven determinations of 4.7% and 2.7% under optimum conditions. The maximum preconcentration factor was 100 for triazines when 500 mL of sample solution volume was used. The linear ranges of calibration curves for atrazine and simazine were 1-150 ng mL(-1) and 1-300 ng mL(-1), respectively, with correlation coefficients of 0.999 and the detection limits (3Signal-to-Noise) were 0.24 ng mL(-1) and 0.21 ng mL(-1) for atrazine and simazine. The capacity of the adsorbent was also examined and found to be 0.8 mg g(-1) and 1.3 mg g(-1) for atrazine and simazine, respectively. The proposed method was successfully applied to the determination of triazines in river water and tap water samples with high precision and accuracy. PMID- 17723675 TI - A new tool for inorganic nitrogen speciation study: simultaneous determination of ammonium ion, nitrite and nitrate by ion chromatography with post-column ammonium derivatization by Nessler reagent and diode-array detection in rain water samples. AB - The paper presents a new method for a simultaneous determination of inorganic nitrogen species in the oxidized (NO2-, NO3-) and reduced (NH4+) form in rain water samples. The method is based on a system of nitrogen species separation employing ion exchange and diode-array detection. The ions are separated in a strong ion-exchanger, nitrites and nitrates are determined directly at 208 and 205 nm, respectively, while the ammonium ions are determined in the column hold up time after a post-column derivatization by the Nessler reagent, at 425 nm. The use of a diode-array detector permits a simultaneous identification of the inorganic nitrogen species in 8 min. The detection limits obtained are: NO2-, 0.1 mg L(-1); NO3-, 0.05 mg L(-1); NH4+, 1 mg L(-1). The method proposed has been successfully used for speciation analysis of inorganic nitrogen in precipitation. PMID- 17723676 TI - Selective solid-phase extraction of nickel(II) using a surface-imprinted silica gel sorbent. AB - A new Ni(II)-imprinted amino-functionalized silica gel sorbent with excellent selectivity for nickel(II) was prepared by an easy one-step reaction by combining a surface imprinting technique for selective solid-phase extraction (SPE) of trace Ni(II) in water samples prior to its determination by inductively coupled plasma atomic emission spectrometry (ICP-AES). Compared with non-imprinted polymer particles, the ion-imprinted polymers (IIPs) had higher selectivity and adsorption capacity for Ni(II). The maximum static adsorption capacity of the ion imprinted and non-imprinted sorbent for Ni(II) was 12.61 and 4.25 mg g(-1), respectively. The relatively selective factor (alpha(r)) values of Ni(II)/Cu(II), Ni(II)/Co(II), Ni(II)/Zn(II) and Ni(II)/Pd(II) were 45.99, 32.83, 43.79 and 28.36, which were greater than 1. The distribution ratio (D) values of Ni(II) imprinted polymers for Ni(II) were greatly larger than that for Cu(II), Co(II), Zn(II) and Pd(II). The detection limit (3sigma) was 0.16 ng mL(-1). The relative standard deviation of the method was 1.48% for eight replicate determinations. The method was validated by analyzing two certified reference materials (GBW 08618 and GBW 08402), the results obtained is in good agreement with standard values. The developed method was also successfully applied to the determination of trace nickel in plants and water samples with satisfactory results. PMID- 17723677 TI - Determination of selected polychlorinated biphenyls in soil by miniaturised ultrasonic solvent extraction and gas chromatography-mass-selective detection. AB - Miniaturised ultrasonic solvent extraction procedure was developed for the determination of selected polychlorinated biphenyls (PCBs) in soil samples by gas chromatography-mass-selective detection by using 2(3) factorial experimental design. Recoveries of PCBs from fortified soil samples are over 90% for three different fortification levels between 40 and 120 microg kg(-1), and relative standard deviations of the recoveries are below 7%. The limits of detection (LODs) ranged from 0.003 to 0.006 microg kg(-1). The performance of the proposed method was compared to traditional shake flask extraction method on the spiked real soil sample and extraction methods showed comparable efficiencies. Proposed miniaturised ultrasonic solvent extraction offers several advantages, i.e., reducing sample requirement for measurement of target compound, less solvent consumption and reducing the costs associated with solvent purchase and waste disposal. PMID- 17723678 TI - Laser induced thermal lens spectrometry for cobalt determination after cloud point extraction. AB - A new approach, employing cloud point extraction (CPE) in combination with thermal lens spectrometry (TLS), has been developed for the determination of cobalt. The CPE and TLS methods have good matching conditions for combination because TLS is suitable for low volume samples obtained after CPE and for organic solvents, which are used for dissolving the remaining analyte phase. 1-(2 Pyridylazo)-2-naphthol (PAN) was used as a complexing agent and octylphenoxypolyethoxyethanol (Triton X-114) was added as a surfactant; then the pH of solution was adjusted. After phase separation at 50 degrees C based on the cloud point extraction of the mixture, the surfactant-rich phase was dried and the remaining phase was dissolved using 20 microL of carbon tetrachloride. The obtained solution was introduced into the quartz micro cell and the analyte was determined by thermal lens spectrometry. The He-Ne laser (632.8 nm) was used as both the probe and the excite source. Under optimum conditions, the analytical curve was linear for the concentration range of 0.2-40 ng mL(-1) and the detection limit was 0.03 ng mL(-1). The enhancement factor of 470 was achieved for a 10 mL sample. Relative standard deviations were lower than 5%. The method was successfully applied to the extraction and determination of cobalt in tap, river and sea water. PMID- 17723679 TI - Enhanced plasmon resonance light scattering signals of colloidal gold resulted from its interactions with organic small molecules using captopril as an example. AB - Gold nanoparticles are known for their plasmon resonance absorption (PRA) depending on their size. Our this investigation shows that plasma resonance light scattering (PRLS) signals in the corresponding PRA region could be measured using a common spectrofluorometer, and be enhanced when aggregation of gold nanoparticles occurs due to their interaction with organic small molecules (OSMs). Using captopril (Cap) as an example, we investigated the interactions of gold nanoparticles with OSMs in order to propose a general method of OSMs such as typical clinic organic drugs. In aqueous medium of pH 2.09, there are about 2.2 x 10(3) Cap molecules covalently binding to the surface of a 10-nm diameter gold nanoparticle through the thiol functional group of Cap, and thus forms a core shell assembly of [(Au)(31000)]@[(Cap)(2200)], displaying strong enhanced PRLS signals in the PRA region of gold colloid. The PRLS intensities characterized at 553.0 nm were found to be proportional to the concentration of Cap over the range of 0.1-1.7 mg L(-1) with the determination limit (3sigma) of 32.0 microg L(-1). With that, Cap in pharmaceutical preparations could be determined with the recovery of 97.0-104.5% and R.S.D. of less than 2.4%. PMID- 17723680 TI - Baseline isotopic data of polyhalogenated compounds. AB - The delta2H- and delta13C-values of polyhalogenated compounds were determined by EA-IRMS. Most of the compounds were related to the chloropesticides DDT and its metabolites, hexachlorocyclohexanes, and toxaphene, as well as several polybrominated compounds such as bromophenols and -anisoles. delta2H-values ranged between -235 per thousand and +75 per thousand whereas delta13C-values were found in the range -22 per thousand to -38 per thousand. No correlation between delta2H- and delta13C-values could be identified. Comparative analysis clarified that bromophenols and the corresponding bromoanisoles may vary in their isotopic distribution. 2H NMR was used to quantify abundances of 2H isotopomers. Quantification of isotopomers of 2,4-dibromophenol and 2,4-dibromoanisole proved that both compounds from different suppliers do not originate from the same source. Differences in the delta2H-values of two toxaphene products were further investigated by the synthesis of products of different degree of chlorination from camphene. It was shown that the delta13C-values remained mostly unaltered as was expected since no carbon is lost in this procedure. However, the reaction products became enriched in 2H with increasing degree of chlorination. Different delta2H-values of the starting material will also impact the delta2H-values of the chlorination products. PMID- 17723681 TI - Determination of cationic surfactants in pharmaceuticals based on competitive aggregation in ternary amphiphile mixtures. AB - The surfactant to dye binding degree (SDBD) method was extended for the first time to the determination of cationic amphiphiles. For this purpose, Cresyl Violet (CV) and sodium dodecylsulphate (SDS) were selected as dye and reactant surfactant, respectively. This chemical system was used for the determination of cationic surfactants in pharmaceuticals. The approach was based on the competition established between the dye and cationic analytes to form mixed aggregates with the anionic surfactant (SDS-CV and SDS-analyte), which resulted in an increase of the amount of SDS required to reach a given SDS-CV binding degree. The feasibility of the proposed method to determine quaternary ammonium surfactants belonging to different structural groups (alkyldimethylbenzylammonium chlorides, alkyltrimethylammonium bromides and alkylpyridinium chlorides) in a wide variety of pharmaceutical formulations (solutions, creams and powders) was proved. The analytical features of the SDBD method (versatility, high precision and selectivity, ruggedness, rapidity, simplicity and low cost) made it an advantageous alternative to the conventional methods used in cationic surfactant quality control. PMID- 17723683 TI - Improved surface-enhanced Raman scattering on optimum electrochemically roughened silver substrates. AB - In this work, the effects of preparation conditions used in roughening silver substrates by electrochemical triangular-wave oxidation-reduction cycles (ORC) on surface-enhanced Raman scattering (SERS) were first investigated. The optimum roughening conditions for obtaining strongest SERS of Rhodamine 6G (R6G) are as follows. Ag electrodes were cycled in deoxygenated aqueous solutions containing 0.1 M NaCl from -0.3 to +0.2 V versus Ag/AgCl at 25 mV s(-1) for five scans. The SERS of R6G adsorbed on this optimum procedure-prepared roughened Ag substrate exhibits a higher intensity by one order of magnitude, as compared with that of R6G adsorbed on a normally roughened Ag substrate. PMID- 17723682 TI - Fluorescence water sensor based on covalent immobilization of chalcone derivative. AB - A new fluorescence sensor for determining water content in organic solvents has been successfully demonstrated based on a fluorescent dye. 4'-N,N-dimethylamino-4 methylacryloylamino chalcone (DMC), in which the charge donor and acceptor parts were both contained, was copolymerized with acrylamide, hydroxyethyl methacrylate and triethylene glycol dimethacrylate onto glass surface. The fluorescence intensity of DMC decreased with increasing of water content in organic solvents owing to the formation of solvate complexes. DMC fluorescence intensity changed as a linear function of water content in the range of 0-6% in the samples of acetone, ethanol, and acetonitrile solutions. Satisfactory reproducibility, reversibility and a short response time were realized. With the optimum membrane described, detection limits were of 0.006%, 0.008%, and 0.002% for acetone, ethanol, and acetonitrile, respectively. The sensing membrane was found to have a lifetime at least 2 months. PMID- 17723684 TI - Analytical methods for the characterization of surface finishing in bricks. AB - The recent restoration works of Santo Stefano Church Facade (XV century) in Venice have shown traces variously saved of different kind of surface finishes. These finishes were found on the brick's surface both in the masonry and in the decorative elements. Different brick's surface and decorative tile samples were investigated using several techniques: optical microscopy, scanning electron microscopy, thermal analysis, infrared spectroscopy and reflectance Fourier transform infrared microspectroscopy. The evaluation of the reached results was used to understand the decorative techniques and to recognize the material employed. PMID- 17723685 TI - 13C nuclear magnetic resonance spectroscopy to determine olive oil grades. AB - 13C nuclear magnetic resonance spectroscopy was used in a first attempt to differentiate olive oil samples by grades. High resolution 13C NMR Distortionless Enhancement by Polarization Transfer (DEPT) spectra of 137 olive oil samples from the four grades, extra virgin olive oils, olive oils, olive pomace oils and lampante olive oils, were measured. The data relative to the resonance intensities (variables) of the unsaturated carbons of oleate (C-9 and C-10) and linoleate (L-9, L-10 and L-12) chains attached at the 1,3- and 2-positions of triacylglycerols were analyzed by linear discriminant analysis. The 1,3- and 2- carbons of the glycerol moiety of triacylglycerols along with the C-2, C-16 and C 18 resonance intensities of saturated, oleate and linoleate chains were also analyzed by linear discriminant analysis. The three discriminanting functions, which were calculated by using a stepwise variable selection algorithm, classified in the true group by cross-validation procedure, respectively, 76.9, 70.0, 94.4 and 100% of the extra virgin, olive oil, olive pomace oil and lampante olive oil grades. PMID- 17723686 TI - Direct determination of impurities in high purity silicon carbide by inductively coupled plasma optical emission spectrometry using slurry nebulization technique. AB - A novel method for the determination of Al, Ca, Cr, Cu, Fe, Mg, Mn, Ni and Ti in high purity silicon carbide (SiC) using slurry introduction axial viewed inductively coupled plasma optical emission spectrometry (ICP-OES) was described. The various sizes of SiC slurry were dispersed by adding dispersant polyethylene imine (PEI). The stability of slurry was characterized by zeta potential measurement, SEM observation and signal stability testing. The optimal concentration of PEI was found to be 0.5 wt% for the SiC slurry. Analytical results of sub-mum size SiC by the slurry introduction were in good accordance with those by the alkaline fusion method which verified that determination could be calibrated by aqueous standards. For mum size SiC, results of most elements have a negative deviation and should be calibrated by the Certified Reference Material slurry. Owing to a rather low contamination in the sample preparation and stability of the slurry, the limits of detection (LODs), which are in the range of 40-2000 ng g(-1), superior to those of the conventional nebulization technique by ICP-OES or ICP-MS. PMID- 17723688 TI - A galactose polyacrylate-based hydrogel scaffold for the detection of cholera toxin and staphylococcal enterotoxin B in a sandwich immunoassay format. AB - A galactoside-based polyacrylate hydrogel was used as a scaffold to immobilize antibodies for the development of a sandwich immunoassay to detect cholera toxin (CT) and staphylococcal enterotoxin B (SEB). The hydrogel possesses large pores and simulates a solution-like environment allowing easy penetration of large biomolecules. Highly crosslinked hydrogels containing pendant amine or carboxyl functionalities were polymerized through a free-radical polymerization process. Covalent crosslinking of the antibodies on hydrogel films was accomplished using a homobifunctional crosslinker or carbodiimide chemistry. Utilizing the two different crosslinking methodologies, our results demonstrated the effectiveness of repetitive additions of crosslinker reactant into a single location on the gel surface. This approach in fact increased the amount of immobilized antibody. Patterned arrays of the immobilized antibodies for sandwich immunoassay development were achieved using a PDMS template containing micro-channels. This template provided a suitable means for applying reagents in multiple cycles. Fluorescence and three-dimensional (3D) imaging by confocal microscopy and laser scanning confocal microscopy of Cy3-labeled anti-CT and/or Cy3-anti-SEB tracer molecules provided qualitative and quantitative measurements on the efficiency of protein immobilization, detection sensitivity and signal-to-noise ratios. As a result of using the galactose polyacrylate-base hydrogel as a platform for immunoassay development, we have successfully been able to achieve low limits of detection for SEB and cholera toxins (1.0 ng mL(-1)). Repetitive additions (>3 cycles) of the crosslinker and antibody have also shown a dramatic increase in the immobilization of antibody resulting in improved immunoassay sensitivity. Fluorescence signal-to-noise ratios using the hydrogel-based immunoassays have been observed as high a 40:1. PMID- 17723689 TI - Colorimetric multiplexed immunoassay using specific aggregation of antigenic peptide-modified luminous nanoparticles. AB - A rapid immunoassay capable of detecting specific antibodies in one-step procedure is described. Antigenic peptides with cationic (KKKKC) or anionic (DDDDC) pentamer tail were immobilized on luminous nanospheres of 40 nm diameter (O) through cystamine and bifunctional linker molecules under various conditions. The numbers of each peptide anchored to a sphere were 5.0 x 10(2) and 0.8-3.8 x 10(3), respectively. A mixture of the antigenic peptides of FAK and c-Myc was immobilized to the spheres with red emission, while that of c-Myc and alpha catenin was likewise to green spheres. Multiplexed immunoassay was easily achieved by adding the antibodies to a mixed dispersed solution of these spheres under appropriate conditions. Anti-FAK and anti-alpha-catenin antibodies formed aggregates with red and green emissions, respectively. On the other hand, the anti-c-Myc antibody formed aggregates emitting a yellow light. This system enabled us to differentiate three antibodies in one vessel from the definite differences in aggregate color. PMID- 17723690 TI - Development of a chemiluminescent immunosensor for chloramphenicol. AB - A direct competitive chemiluminescent immunosensor system that exploits the competition between chloramphenicol (CAP) as an analyte and CAP-horseradish peroxidase conjugate as a tracer for binding to an anti-CAP antibody on a solid support was devised by installing a flow-through cell which was connected to an injector and a peristaltic pump inside a dark box, followed by positioning a photomultiplier tube as light detector in front of it. The anti-CAP antibody was immobilized onto positively charged Biodyne B membrane pieces by a dipping procedure. The operating conditions for the immunosensor were selected with respect to substrate composition (0.25, 13.3 and 0.66 mM for luminol, H2O2 and p iodophenol, respectively), injection volume of the substrate solution (200 microL) and the concentrations of antibody for immobilization (0.10 mg mL(-1)) and tracer (0.030 mg mL(-1)). At these conditions, sensor response according to analyte concentration was well fitted to a linear equation when plotted in semi logarithmic scale, with the limit of detection for CAP of 10(-8) M. By using the immunosensor, CAP measurement in the model samples prepared from five food materials was conducted. PMID- 17723691 TI - Identification of P-glycoprotein substrates using open tubular chromatography on an immobilized P-glycoprotein column: Comparison of chromatographic results with Caco-2 permeability. AB - The Caco-2 cell monolayer model was used to classify 13 compounds as P glycoprotein (Pgp) substrates or non-substrates. The apparent permeability coefficients (Papp) in the basal-to-apical direction (Papp(B-A)) and in the apical-to-basal direction (Papp(A-B)) were determined for each compound and a compound was designated as a Pgp substrate if Papp(B-A)/Papp(A-B), the permeability ratio, exceeded 2.0. The same compounds were chromatographed on open tubular glass columns containing membranes from cell lines that either expressed Pgp (Pgp+-OT column) or did not express Pgp (Pgp(-)-OT column). The differential retentions in min, Deltat values, of the compounds were determined using the following relationship Deltat=t((Pgp(+)-OT))-t((Pgp(-)-OT)). A statistically significant correlation was observed between the Deltat values and the permeability ratios, r2=0.7749 (p=0.0063), indicating that the differential chromatography approach could be used to quantitatively assess permeability ratios. The results also indicated that a Deltat value > or =0.5 min was a reliable measure of a permeability ratios >2 and could be used as a rapid qualitative determination of whether a test compound was a Pgp substrate. The chromatographic study took 1h to complete and a single pair of columns could be used to screen at least 150 compounds a week and 600 compounds during the 4-week lifetime of the columns. PMID- 17723692 TI - Capillary electrophoresis for capture and concentrating of target nucleic acids by affinity gels modified to contain single-stranded nucleic acid probes. AB - Selective capture and pre-concentration of target nucleic acids from relatively complicated samples may provide a method to facilitate introduction to a microfluidic-based detection system to improve detection limits. An acrylamide polymer gel modified with Acrydite that contained 20mer oligonucleotide probe was prepared and loaded into a capillary column. The results indicated that the amount of probe DNA that was captured into the acrylamide was about 40% of the starting monomer, and different quantities of probe could therefore be coupled into the gel. The gel was passivated by pre-treatment with non-complementary DNA oligonucleotide to block non-selective adsorption sites, and the gel was determined to be stable for multiple cycles of use. The probe could hybridize with target sequences that were introduced by electrokinetic injection from a sample solution. The target could be freed from the polymer gel by use of a combination of heating, chaotropic salt and voltage conditions. Target capture efficiency was up to 90% when using samples that did not saturate probe sites in the columns, and recovery of target from the gel could be as high as 95%. PMID- 17723693 TI - High sensitivity detection of bisphenol A using liposome chromatography. AB - An antibody column in tandem with a fluorescent dye entrapped liposome column was developed for highly sensitive detection of an endocrine disruptor, bisphenol A (BPA). Anti-BPA antibody was immobilized in a protein G column with orientation control. A derivative of BPA was conjugated to phospholipase A2 (PLA2). BPA sample solutions mixed with the BPA-PLA2 conjugates were injected on to the anti BPA antibody column and competitive binding occurred in the antibody column. The amount of the free conjugate was proportional to the concentration of the BPA sample. The eluted conjugates were injected on to the second column gel on which calcein-entrapped liposomes were immobilized and the PLA2-catalyzed hydrolysis of liposomal phospholipids causing fluorescent dye leakage as a signal amplification. In this system, the mixture of BPA and BPA-PLA2 conjugate were incubated for 60 min in the anti-BPA column, and then the collected solution was applied to the liposome column. The BPA detection range of 0.02-140 ng mL(-1) was wider than 0.03-6.6 ng mL(-1) obtained by the method of competitive ELISA using the same antibody. Moreover, this system could be adapted to an HPLC system resulting in almost the same detection limit in online detection. The method could be applied to environmental samples, river water and soil extracts. The BPA concentration of 0.1 ng mL(-1) and 10 ng g(-1) was detectable in water and soil extract, respectively. PMID- 17723694 TI - Capturing molecules with templated materials--analysis and rational design of molecularly imprinted polymers. AB - The creation of synthetic tailor-made receptors capable of recognizing desired molecular targets with high affinity and selectivity is a persistent long-term goal for researchers in the fields of chemical, biological, and pharmaceutical research. Compared to biomacromolecular receptors, these synthetic receptors promise simplified production and processing, less costs, and more robust receptor architectures. During recent decades, molecularly imprinted polymers (MIPs) are widely considered mimics of natural molecular receptors suitable for a diversity of applications ranging from biomimetic sensors, to separations and biocatalysis. A remaining challenge for the next generation of MIPs is the synthesis of deliberately designed and highly efficient receptor architectures suitable for recognizing biologically relevant molecules, for which natural receptors are either not prevalent, or difficult to isolate and utilize. Hence, this review discusses recent advances in synthetic receptor technology for biomolecules (e.g. drugs, amino acids, steroids, proteins, entire cells, etc.) via molecular imprinting techniques. Surface imprinting methods and epitope imprinting approaches have been introduced for protein recognition at imprinted surfaces. Imprinting techniques in aqueous solution or organic-water co-solvents have been introduced avoiding denaturation of biomolecules during MIP synthesis. In addition, improved bioreactivity of entire enzyme or active site mimics generated by molecular imprinting will be highlighted. Finally, the emerging importance of molecular modeling and molecular dynamics studies detailing the intermolecular interactions between the template species, the porogenic solvent molecules, and the involved monomer and cross-linker in the pre-polymerization solution will be addressed yielding a rational approach toward next-generation MIP technology. PMID- 17723695 TI - Prospects of conducting polymers in biosensors. AB - Applications of conducting polymers to biosensors have recently aroused much interest. This is because these molecular electronic materials offer control of different parameters such as polymer layer thickness, electrical properties and bio-reagent loading, etc. Moreover, conducting polymer based biosensors are likely to cater to the pressing requirements such as biocompatibility, possibility of in vivo sensing, continuous monitoring of drugs or metabolites, multi-parametric assays, miniaturization and high information density. This paper deals with the emerging trends in conducting polymer based biosensors during the last about 5 years. PMID- 17723696 TI - Electronic deoxyribonucleic acid (DNA) microarray detection of viable pathogenic Escherichia coli, Vibrio cholerae, and Salmonella typhi. AB - An electronic deoxyribonucleic acid (DNA) microarray technique was developed for detection and identification of viable Escherichia coli O157:H7, Vibrio cholerae O1, and Salmonella typhi. Four unique genes, the E. coli O157 lipopolysaccharide (LPS) gene (rfbE) and H7 flagellin gene (fliC), the V. cholerae O1 LPS gene (rfbE), and the S. typhi LPS gene (tyv), were chosen as the targets for detection. These targets were selectively amplified from mRNA of viable cells using reverse transcription polymerase chain reaction (RT-PCR) and detected using the electronic DNA microarray technique. Specific captures and reporters were designed and examined for selective detection and correct identification of the target pathogens. The technique was able to detect as few as 2-150 cells of E. coli O157:H7. The co-presence of six other common bacteria and a parasite at 10- and 1000-fold higher concentrations than the target E. coli O157:H7 did not interfere with the specific detection. Comparative analysis of live and heat killed E. coli O157:H7 cells showed that the technique only responded to the viable cells and not to the dead cells. Thus, the integration of RT-PCR of specific mRNA with the electronic DNA microarray technique enables specific and sensitive detection of viable target cells. This technique is potentially useful for high throughput screening of multiple pathogenic bacteria in different samples. PMID- 17723697 TI - Ferrocenylnaphthalene diimide-based electrochemical detection of methylated gene. AB - Ferrocenylnaphthalene diimide (FND)-based electrochemical hybridization assay was applied to the detection of methylated cytosine of DNA using the products obtained after treatment with bisulfite followed by polymerase chain reaction (PCR), where unmethylated cytosine is converted to thymine and methylated one to cytosine. Twenty-meric DNA probes for the methylated (cytosine) and unmethylated (thymine) types of the part of the promoter region of cyclin D-dependent protein kinase inhibitor, p16, gene (p16(Ink4a)) were used to be immobilized on the electrochemical array (ECA) chip. Using 1 microL of 10 ng/microL of methylated sample obtained from the methylation-specific PCR of methylated genome containing 10-times excess of unmethylated one, the methylated PCR sample could be detected by the identical electrochemical signals from the two DNA probes under the settled optimum hybridization conditions. PMID- 17723698 TI - Tetrakis-acridinyl peptide: distance dependence of photoinduced electron transfer in deoxyribonucleic acid assemblies. AB - The distance dependence of photoinduced electron transfer in deoxyribonucleic acid (DNA) duplex was investigated using the "TAP cassette" systems of the general formula (AT)6A(n)XA(9-n) (X denote guanine (G) or cytosine (C)). The tetrakis-9-acridinyl peptide (TAP) binds tightly with (AT)6 duplex region showing strong fluorescence that was not quenched by the A(n)XA(9-n) single-stranded region. Quenching was observed after duplex formation with the complementary T(9 n)XT(n) strand (G-C pairing), showing clear dependence on the distance between the TAP and a guanine. An extremely low beta value of 0.22 was obtained in our electron transfer (ET) system that suggests exceptional good mediation of ET process. Experiments with G-mismatches showed negligible quenching for systems with guanine separated by more than one AT base pair that indicated rather inefficient ET process for duplexes containing disrupted pi-electronic system. PMID- 17723699 TI - Photoactive, covalent attachment of deoxyribonucleic acid on gold with double strand specificity using self-assembled monolayers containing psoralen. AB - Taking advantages of psoralen photochemistry, we have developed a new method of immobilizing DNA on gold substrate surfaces. A psoralen derivative having an alkylamine function was synthesized, and was self-assembled on gold substrate surfaces in a combined use of a thiol-derivatized molecule, 3,3' dithiobis(succinimidyl propionate) forming amide bonds on the surface. We found that by irradiating with long wavelength ultraviolet light (320-400 nm), DNA molecules added in the solution phase were covalently immobilized on the monolayer surface through the photoadduct formation of the psoralen molecules with the DNA nucleobases. The present method has its advantage that is applicable to native DNAs, no chemically modifying DNAs, in spite of its covalent immobilization principle. We have examined 12 mer synthetic oligonucleotide immobilizations and have found that the surface concentration thus attained was to be 20 pmol cm(-2), which is consistent with saturated surface coverage. Interestingly, the immobilization occurred double-stranded-DNA-preferentially; no immobilization for single-stranded DNAs. Characterization of the immobilization chemistry has been achieved using atomic force microscopic imaging, infrared absorption, X-ray photoelectron spectroscopy, electrochemistry, and quartz crystal microbalance and their results were described. PMID- 17723700 TI - Spatiotemporal control of cell adhesion on a self-assembled monolayer having a photocleavable protecting group. AB - Control of cell adhesion is a key technology for cell-based drug screening and for analyses of cellular processes. We developed a method to spatiotemporally control cell adhesion using a photochemical reaction. We prepared a cell culturing substrate by modifying the surface of a glass coverslip with a self assembled monolayer of an alkylsiloxane having a photocleavable 2-nitrobenzyl group. Bovine serum albumin (BSA) was adsorbed onto the substrate to make the surface inert to cell adhesion. When exposed to UV light, the alkylsiloxane underwent a photocleavage reaction, leading to the release of BSA from the surface. Fibronectin, a protein promoting cell adhesion, was added to cover the irradiated regions and made them cell-adhesive. Seeding of cells on this substrate resulted in their selective adhesion to the illuminated regions. By controlling the sizes of the illuminated regions, we formed cell-adhesive spots smaller than single cells and located focal adhesions of the cells. Moreover, by subsequently illuminating the region alongside the cells patterned on the substrate in advance, we released their geometrical confinements and induced migration and proliferation. These manipulations were conducted under a conventional fluorescence microscope without any additional instruments. The present method of cell manipulation will be useful for cell biological studies as well as for the formation of cell arrays. PMID- 17723701 TI - Metal ion-imprinted polymers--novel materials for selective recognition of inorganics. AB - Ion-imprinted polymers (IIPs) are recently identified nano-porous polymeric materials which on leaching the imprint ion can rebind, sense or transport (when cast as membranes) selectively the target analyte in presence of closely related inorganic ions. The IIPs find interesting applications in solid phase extraction, sensors and membrane separations of inorganics. Unlike the molecularly imprinted polymers, the IIP field is in its infancy and has been briefly reviewed here along with some rough guidelines and concepts for further development of IIPs. PMID- 17723702 TI - Determination of total safranal by in situ acid hydrolysis in supercritical fluid media: Application to the quality control of commercial saffron. AB - A procedure allowing hydrolysis reactions to be conducted in a dynamic supercritical-CO2 medium was developed for quantifying total safranal (viz. free safranal present in the sample+safranal resulting from picrocrocin hydrolysis), which are the main component of the essential oil and responsible for the characteristic aroma of saffron. The proposed method allows total safranal amounts over the ranges 0.05-1.5 mg mL(-1) to be determined. The standard deviation achieved was 2%. This method was applied to the determination of safranal in natural saffron samples. The results obtained were compared with the "safranal value" total index, which is widely used as a quality measure of saffron products. The comparison revealed that the proposed method provides useful information not contained in the safranal value, based on the fact that, some samples with a high "safranal index" contain low concentrations of safranal. The proposed method is very useful for quality control in commercial saffron samples. PMID- 17723703 TI - Microwave-assisted extraction through an aqueous medium and simultaneous cleanup by partition on hexane for determining pesticides in agricultural soils by gas chromatography: a critical study. AB - A simple microwave-assisted extraction and partitioning method (MAEP) using water acetonitrile and n-hexane for desorption and simultaneous partitioning, respectively, together with gas chromatography (GC) was studied to determine representative pesticides (trifluralin, metolachlor, chlorpyriphos and triadimefon) with a broad range of physico-chemical properties in agricultural soils. Three points were considered crucial in this study: instrumental and sample-associated factors affecting extraction of the target compounds were studied through experimental design; the spiking procedure at trace levels was carried out to reproduce the solute-soil sorption taking place in the environment as closely as possible; and results were analyzed taking into account the adsorption behaviour of the compounds on different kinds of soils. The complete analytical procedure proposed consisted of the MAEP of pesticides from 1.0 g of soil with 1 mL of 1:1 water/acetonitrile mixture, and 5 mL of hexane for trapping. The microwave heating program applied was 2 min at 250 W and 10 min at 900 W, and 130 degrees C maximum temperature. After extraction, the hexane layer was evaporated to dryness; the residue was re-dissolved and directly analyzed by gas chromatography electron capture detection (GC-ECD). Clean chromatograms were obtained without any additional cleanup step. Besides the four pesticides used to optimise MAEP, the method was applied to determine an additional group of pesticides (triallate, acetochlor, alachlor, endosulphan I and II, endrin, methoxychlor and tetradifon) in different soils. Most of the compounds studied were recovered in good yields with relative standard deviations (R.S.D.s) below 9% and detection limits ranged from 0.004 to 0.036 microg g(-1). The described method is efficient and fast to determine hydrophobic pesticides at ng g(-1) level in soil with different clay-to-organic matter ratios. PMID- 17723705 TI - Glucose biosensor based on the layer-by-layer self-assembling of glucose oxidase and chitosan derivatives on a thiolated gold surface. AB - The work proposed here deals with the design and characterization of biorecognition layers for the amperometric glucose determination based on the self-assembling of new chitosan derivatives, Nafion and glucose oxidase onto thiolated gold electrodes. The supramolecular multistructure is obtained by deposition of a layer of chitosan derivative (quaternized or hydrophobic) onto the gold surface modified with the sodium salt of 3-mercapto-1-propansulfonic acid, followed by the deposition of a layer of Nafion (as anti-interference barrier) and by the alternate deposition of the chitosan derivative and glucose oxidase (as biocatalytic layer). The influence of the deposition time and concentration of polyelectrolytes, organization and number of layers, and nature of the chitosan derivative on the sensitivity and selectivity of the bioelectrode is examined and optimized in order to obtain a rational design of the biosensor. The system is studied electrochemically from the oxidation at 0.700 V of the hydrogen peroxide enzymatically generated using gold as substrate, and spectrophotometrically from the protein absorption at 277 nm using quartz as substrate. The selected biosensor containing five quaternized chitosan/glucose oxidase bilayers exhibits very good analytical performance with a sensitive ((4.9+/-0.2) x 10(2) nA mM(-1)) and highly selective response (0% interference for maximum physiological levels of ascorbic acid and uric acid), demonstrating that the alternate electrostatic adsorption of conveniently selected polyelectrolytes allows noticeable improvements in the selectivity and sensitivity of a biosensor. PMID- 17723704 TI - Expression and characterization of insulin growth factor-I-enhanced green fluorescent protein fused protein as a tracer for immunoassay. AB - The insulin-like growth factor-I (IGF-I) is an important polypeptide hormone under investigation for body metabolism study and for doping detection. Here, we describe for the first time the expression of a recombinant fusion protein of IGF I and the enhanced green fluorescent protein (EGFP). The genetic fusion approach enables preparation of conjugates with 1:1 stoichiometry and homogeneous structure. The fused protein (EGFP-IGF-I) was expressed as a soluble protein in cytoplasm of Escherichia coli and its fluorescence and immunoreaction properties were thoroughly characterized. Finally, we demonstrated the utility of the EGFP IGF-I fusion protein for the fluorescence immunoassay of IGF-1. The linear range of the assay is 1.6 x 10(-8) to 2.0 x 10(-6) M with a detection limit of 1.6 x 10(-8) M. To our knowledge, this is the first time that EGFP has been used as a quantitative label in a fusion protein to develop a quantitative assay for IGF-I. Furthermore, the use of genetically engineered fusion proteins, which combine peptide hormones with fluorescent protein, can lead to a new labeling approach to a number of bioanalytical applications. PMID- 17723706 TI - Organoclay-enzyme film electrodes. AB - This paper aims at showing the interest of organoclays (clay minerals containing organic groups covalently attached to the inorganic particles) as suitable host matrices likely to immobilize enzymes onto electrode surfaces for biosensing applications. The organoclays used in this work were natural Cameroonian smectites grafted with either aminopropyl (AP) or trimethylpropylammonium (TMPA) groups. The first ones were exploited for their ability to anchor biomolecules by covalent bonding while the second category exhibited favorable electrostatic interactions with negatively charged enzymes due to ion exchange properties that were pointed out here by means of multisweep cyclic voltammetry. AP-clay materials were applied to the immobilization of glucose oxidase (GOD) and TMPA clays for polyphenol oxidase (PPO) anchoring. When deposited onto the surface of platinum or glassy carbon electrodes as enzyme/organoclay films, these systems were evaluated as biosensing electrochemical devices for detection of glucose and catechol chosen as model analytes. The advantageous features of these organoclays were discussed by comparison to the performance of related film electrodes made of non-functionalized clays. It appeared that organoclays provide a favorable environment to enzymes activity, as highlighted from the biosensors characteristics and determination of Michaelis-Menten constants. PMID- 17723707 TI - A comparative study of immobilization techniques for urease on glass-pH-electrode and its application in urea detection in blood serum. AB - Different techniques have been used (physical adsorption, physically entrapped sandwich and microencapsulation) for the immobilization of urease enzyme in tetramethylorthosilicate (TMOS) derived sol-gel matrix on the sensing surface of glass-pH-electrode. No significant leaching of enzyme occurs from the microencapsulated and physically entrapped enzyme sandwich films. Potentiometric techniques have been used for the estimation of urea concentration in each instance. Various parameters of biosensor performance have been studied which indicates that microencapsulation technique is a better method of enzyme immobilization in sol-gel films derived from TMOS. The advantage of microencapsulated biosensor over others include higher sensitivity (dpH/dp(C)=2.4), lower detection limit of 52 microg mL(-1), larger linear range (0.01-30 mM) of urea determination and reasonably long-term stability of about 25 days with 80% response signal. PMID- 17723708 TI - Organophosphorus insecticides extraction and heterogeneous oxidation on column for analysis with an acetylcholinesterase (AChE) biosensor. AB - This paper presents an analysis method for organophosphorus insecticides based on AChE biosensors coupled with a preconcentration and oxidation on a solid phase column. Three organic solvents, acetonitrile (ACN), ethanol and methanol were tested for their influence on AChE activity, insecticide inhibition and their ability to elute the adsorbed insecticides. Our results showed that ACN in a concentration of 5% (v/v) had the less negative effect on biosensor analysis and was the most appropriate organic solvent for the column elution. The presence of the organic solvent in the incubation media of the biosensor was found to induce a reduction of the inhibition percentages. The inhibition of the biosensors was performed in phosphate buffer with 5% (v/v) ACN, while the initial and remaining response of the biosensors were measured in PBS. In these conditions, the LODs of paraoxon and dichlorvos were measured with or without a preconcentration step. The LODs of the AChE biosensor without sample preconcentration were 8 x 10(-8) M for paraoxon and 1 x 10(-7) M dichlorvos and the LOD obtained after the preconcentration step were 2.5 x 10(-8) M for paraoxon and 2.5 x 10(-8) M for dichlorvos. Moreover, the use of the column allowed the heterogeneous oxidation of organophosphorus insecticides for improved LOD. PMID- 17723709 TI - A chemometric approach based on a novel similarity/diversity measure for the characterisation and selection of electronic nose sensors. AB - Electronic nose sensor signals provide a digital fingerprint of the product in analysis, which can be subsequently investigated by means of chemometrics. In this paper, the fingerprint characterisation of electronic nose data has been studied by means of a novel chemometric approach based on the partial ordering technique and the Hasse matrix. This matrix can be associated to each data sequence and the similarity between two sequences can be evaluated with the definition of a distance between the corresponding Hasse matrices. Since all the signals achieved along time are intrinsically ordered, the data provided by electronic nose can be also considered as sequential data and consequently characterized by means of the proposed approach. The similarity/diversity measure has been here applied in order to characterize the class discrimination capability of each electronic nose sensor: extra virgin olive oil samples of different geographical origin have been considered and Hasse distances have been used to select the sensors which appear more able to discriminate the olive oil origins. The distance based on the Hasse matrix has showed some useful properties and proved to be able to link each electronic nose time profile to a meaningful mathematical term (the Hasse matrix), which can be consequently studied by multivariate analysis. PMID- 17723710 TI - The application of Kriging and empirical Kriging based on the variables selected by SCAD. AB - The commonly used approach for building a structure-activity/property relationship consists of three steps. First, one determines the descriptors for the molecular structure, then builds a metamodel by using some proper mathematical methods, and finally evaluates the meta-model. Some existing methods only can select important variables from the candidates, while most metamodels just explore linear relationships between inputs and outputs. Some techniques are useful to build more complicated relationship, but they may not be able to select important variables from a large number of variables. In this paper, we propose to screen important variables by the smoothly clipped absolute deviation (SCAD) variable selection procedure, and then apply Kriging model and empirical Kriging model for quantitative structure-activity/property relationship (QSAR/QSPR) research based on the selected important variables. We demonstrate the proposed procedure retains the virtues of both variable selection and Kriging model. PMID- 17723711 TI - Arsenic speciation analysis of human urine using ion exchange chromatography coupled to inductively coupled plasma mass spectrometry. AB - A sensitive and robust method for the determination of seven inorganic and organic arsenic species was developed using ion exchange chromatography combined with inductively coupled plasma mass spectrometry (IC-ICP-MS). Both anion and cation exchange columns were used in a complementary fashion. Arsenite (As(III)), arsenate (As(V)), monomethylarsonic acid (MMA(V)) and dimethylarsinic acid (DMA(V)) were selectively separated by an anion exchange column using sodium hydroxide (NaOH) gradient elution, while monomethylarsonous acid (MMA(III)), dimethylarsinous acid (DMA(III)) and arsenobetaine (AsB) were separated by a cation exchange column using 70 mM nitric acid as the mobile phase. Baseline separation, high repeatability and low detection limits (0.10-0.75 ng mL(-1)) were achieved. The spiked urine samples were analyzed with this method to evaluate the matrix effect on the method. The results suggest 1-10 dilutions should be made to urine samples before sample injection for the anion exchange analysis to minimize the matrix effect. To validate the method, a new standard reference material (NIST SRM-2670a) was also analyzed. The arsenic species in NIST SRM-2670a were determined by this method, and the sum of their concentrations agreed well with the total arsenic content certified for NIST SRM 2670a. Moreover, this method was applied to measure arsenic species in urine samples from one subject living in New Jersey who drank well water contaminated with arsenic. By this method, two key arsenic metabolites, MMA(III) and DMA(III), were found to be present in these urine samples, which has previously been rarely reported. PMID- 17723712 TI - Speciation of nickel in surface waters measured with the Donnan membrane technique. AB - The evaluation of the ecotoxicological risk of nickel (Ni) in surface water is hampered by a lack of speciation data. Six surface waters were sampled and speciation of Ni(II) was measured by the Donnan membrane technique (DMT) combined with radiochemical determination of 63Ni. The free Ni2+ ion fraction in the dissolved (<0.45 microm) phase was determined at background Ni concentration ((4 8) x 10(-8) M) and at concentrations in the range of toxicity thresholds for the Ni sensitive species Cerodaphnia dubia (5 x 10(-8) to 2 x 10(-6) M). The free ion fraction ranged from 4 to 45% at background Ni and increased with increasing Ni concentration and water hardness and with decreasing pH. The equilibration time after addition of Ni2+ (3h-7d) did not significantly change the measured free ion fraction. Predictions of the Humic-Ion Binding Model WHAM (Windermere Humic Aqueous Model) VI overestimated the observed free Ni2+ fraction (median>two fold), even when assuming that all dissolved organic matter (DOM) was present as fulvic acid (FA). The impact of several model parameters affecting the prediction of Ni speciation were evaluated, including the solubility product of Fe(OH)3, which affects the Fe competition for complexation by DOM. The best fit (R2=0.88) was obtained by increasing only the distribution term DeltaLK2, which modifies the binding strength of multi-dentate sites, to accommodate the observed dependence of free ion fraction on Ni concentration. PMID- 17723713 TI - Determination of tributyltin and 4-hydroxybutyldibutyltin chlorides in seawater by liquid chromatography with atmospheric pressure chemical ionization-mass spectrometry. AB - A liquid chromatographic method is described for the simultaneous determination of tributyltin (TBT) and the hydroxylated intermediate 4-hydroxybutyldibutyltin (OHBuDBT). Separation was achieved in reverse phase mode on a cyanopropyl-bonded silica column under a gradient elution. Various organic solvents and additives were tested and the optimum composition of the mobile phase contained methanol, water, formic acid and tropolone as a complexing agent. Butyltin compounds were detected with an ion trap mass spectrometer interfaced to a liquid chromatograph with an atmospheric pressure chemical ionization source (LC-APCI-MS). Identification and fragmentation pattern of OHBuDBT chloride in full scan MS and MS/MS are reported for the first time using LC-APCI-MS. Gas chromatography-mass spectrometry (GC-MS) spectrum of the same compound is also reported for the first time for comparison purpose. This method allowed limits of detection (LOD) of 35 and 26 ng mL(-1) for TBT and OHBuDBT, respectively, based on successive injections of 10 microL of blank seawater extract. A liquid-liquid extraction procedure using n-hexane-ethyl acetate was developed for the simultaneous analysis of TBT and OHBuDBT chlorides in natural seawater and allowed average recoveries from 72 to 96% for the two compounds at three different spiking levels. PMID- 17723714 TI - Flame atomic absorption spectrometric determination of cadmium(II) and lead(II) after their solid phase extraction as dibenzyldithiocarbamate chelates on Dowex Optipore V-493. AB - An enrichment procedure for cadmium and lead after their solid phase extraction as dibenzyldithiocarbamate chelates on Dowex Optipore V-493 has been established prior to their flame atomic absorption spectrometric determinations. The analytical parameters including pH, amounts of dibenzyldithiocarbamate, sample volume, etc., were investigated. The effects of alkaline and earth alkaline ions and some metal ions on the retentions of analytes on Dowex Optipore V-493 resin were examined. Under the optimized conditions, the detection limits (3s, n=21) for cadmium and lead were 0.43 microg L(-1) and 0.65 microg L(-1), respectively. The relative standard deviation (R.S.D.), and the recoveries of standard addition for this method were lower than 5% (n=11) and 95-102%, respectively. Three standard reference samples (LGC 6010 Hard drinking water, NIST SRM 2711 Montana soil and GBW 07605 Tea) were introduced for accuracy and precision of analytical data. The proposed solid phase extraction system was successfully applied to the analysis of environmental samples. PMID- 17723715 TI - Chromatographic determination of flumequine in food samples by post-column derivatisation with terbium(III). AB - The potential usefulness of terbium(III) as reagent for the luminescent determination of flumequine residues in food samples has been studied using both fluorescence (FL) and time-resolved (TR) modes and both batch (B) and integrated liquid chromatography (LC)/derivatisation approaches. The system was optimised in each instance to establish the analytical features of the four methods. The dynamic ranges of the calibration graphs, obtained with standard solutions of flumequine, were (ng mL(-1)): B-FL 0.18-600; B-TR 2.4-150; LC-FL 3.7-1000 and LC TR 52-3000. The detection limits were also obtained giving the following values (ng mL(-1)): B-FL 0.055; B-TR 0.7; LC-FL 1.1 and LC-TR 15. The precision, expressed as the percentage of relative standard deviation, was equal or lower than 5.1% in all instances. The LC methods, which avoid the interference of other quinolone antibiotics, were applied to the analysis of chicken muscle and liver, and whole milk samples. The sample pre-treatment only consisted of a deproteinisation step. The validation procedure for the analysis of samples was carried out using EC recommendations, and the decision limit and detection capability were calculated. The recoveries obtained ranged from 95.0% to 103.8%. PMID- 17723716 TI - Determination of capsaicinoids in peppers by microwave-assisted extraction-high performance liquid chromatography with fluorescence detection. AB - A new method has been developed for the extraction of capsaicinoids (nordihydrocapsaicin, capsaicin, dihydrocapsaicin, homocapsaicin and homodihydrocapsaicin) in peppers employing microwave-assisted extraction. The parameters studied are: extraction solvent (methanol, ethanol, acetone, ethyl acetate and water), temperature (50-200 degrees C), sample quantity (0.1-1 g), volume of solvent (15-50 mL) and the extraction time (5-20 min). The results found for the optimum conditions are: 125 degrees C as extraction temperature, 25 mL of solvent, 0.5 g of freshly triturated peppers and extraction for 5 min, employing 100% ethanol as solvent. The capsaicinoids obtained were stable under the optimised extraction conditions. The resulting method presents a high degree of reproducibility (R.S.D.<6%). PMID- 17723717 TI - Direct determination of acrylamide in food by gas chromatography-high-resolution time-of-flight mass spectrometry. AB - Simple and rapid gas chromatographic (GC) method employing a high-resolution time of-flight mass analyzer that enables direct analysis (no derivatization) of acrylamide in various heat-processed foodstuffs has been developed and validated. Co-isolation of acrylamide precursors such as sugars and asparagine, constituting the risk of results overestimation due to additional formation of analyte in hot GC injector, is avoided by the extraction with n-propanol followed by solvent exchange to acetonitrile (MeCN). Introduction of a novel purification strategy, dispersive solid phase extraction, based on addition of primary-secondary amine (PSA) sorbent into deffated extract in MeCN, provides a significant reduction of some abundant matrix co-extracts (mainly free fatty acids). Isotope dilution technique (d3-acrylamide as an internal standard) is employed for compensation of potential target analyte losses and/or matrix-inducted chromatographic response enhancement. Limits of quantifications (LOQs) ranged between 15 and 40 microg kg( 1) and recoveries were between 97 and 108% depending on the examined food matrix. The repeatability of measurements (expressed as relative standard deviation, R.S.D.) was as low as 1.9% for potato crisps containing acrylamide at a level of 1 mg kg(-1). Slightly higher values (R.S.D.<4.0%) were achieved for breakfast cereals and crisp bread with approximately 10 times lower content of this processing contaminant. Trueness of results generated by this new method was demonstrated via FAPAS (Food Analysis Performance Assessment Scheme) interlaboratory proficiency tests. PMID- 17723718 TI - Determination of herbicides by solid phase extraction gas chromatography-mass spectrometry in drinking waters. AB - A solid phase extraction (SPE) method has been optimized for the gas chromatography-mass spectrometry (GC-MS) simultaneous determination of herbicides belonging to the following different families: carbamate (molinate), atrazines (atrazine, propazine, simazine, ametryne, cyanazine, terbutylazine, deethylterbutylazine, deethylatrazine), dinitroaniline (trifluralin, pendimethalin), chloroacetamide (alachlor, metolachlor). Different solid substrates have been compared (C18, cyano, styrene-divinylbenzene, phenyl, graphitic carbon). The type of conditioning and elution solvent, its volume, and the sample flow rate have been considered as variables affecting the recovery yields of the herbicides. The optimized experimental conditions are C18 phase conditioned with 3 mL acetone, loaded with 1L water sample at 5 mL min(-1), and eluted with 3 mL acetone. Good recoveries (included between 79% and 99%) and R.S.D. (included between 2% and 12%) have been obtained for all analytes, except for deethylatrazine whose recovery was 46+/-7%. The recovery of deethylatrazine increases up to 94+/-17% if a non-porous graphitic carbon is coupled to the C18 phase, keeping the other parameters constant as optimized. The optimized method has been successfully checked for the identification and quantitation of the selected herbicides in raw and drinking water samples, with quantitation limits as low as 0.01 microg L(-1), fully in agreement with the current legislation. The method is easily routinable. After development, the method is currently routinely applied for the analysis of herbicides in waters and, up today, more than one thousand samples have been analysed at the "Laboratorio della Societa Metropolitana Acque di Torino" (Laboratory of the Municipal Waterworks of Turin) in charge of the control of drinking water quality in Torino. PMID- 17723719 TI - Identifying constituents in commercial gasoline using Fourier transform-infrared spectroscopy and independent component analysis. AB - A new method is proposed that enables the identification of five refinery fractions present in commercial gasoline mixtures using infrared spectroscopic analysis. The data analysis and interpretation was carried out based on independent component analysis (ICA) and spectral similarity techniques. The FT IR spectra of the gasoline constituents were determined using the ICA method, exclusively based on the spectra of their mixtures as a blind separation procedure, i.e. assuming unknown the spectra of the constituents. The identity of the constituents was subsequently determined using similarity measures commonly employed in spectra library searches against the spectra of the constituent components. The high correlation scores that were obtained in the identification of the constituents indicates that the developed method can be employed as a rapid and effective tool in quality control, fingerprinting or forensic applications, where gasoline constituents are suspected. PMID- 17723720 TI - Pattern recognition analysis of differential mobility spectra with classification by chemical family. AB - Differential mobility spectra for alkanes, alcohols, ketones, cycloalkanes, substituted ketones, and substituted benzenes with carbon numbers between 3 and 10 were obtained from gas chromatography-differential mobility spectrometry (GC DMS) analyses of mixtures in dilute solution. Spectra were produced in a supporting atmosphere of purified air with 0.6-0.8 ppm moisture, gas temperature of 120 degrees C, sample concentrations of approximately 0.2-5 ppm, and ion source of 5 mCi (185 MBq) 63Ni. Multiple spectra were extracted from chromatographic elution profiles for each chemical providing a library of 390 spectra from 39 chemicals. The spectra were analyzed for structural content by chemical family using two different approaches. In the one approach, the wavelet packet transform was used to denoise and deconvolute the DMS data by decomposing each spectrum into its wavelet coefficients, which represent the sample's constituent frequencies. The wavelet coefficients characteristic of the compound's structural class were identified using a genetic algorithm (GA) for pattern recognition analysis. The pattern recognition GA uses both supervised and unsupervised learning to identify coefficients which optimize clustering of the spectra in a plot of the two or three largest principal components of the data. Because principal components maximize variance, the bulk of the information encoded by the selected coefficients is about differences between chemical families in the data set. The principal component analysis routine embedded in the fitness function of the pattern recognition GA acts as an information filter, significantly reducing the size of the search space since it restricts the search to coefficients whose principal component plots show clustering on the basis of chemical family. In a second approach, a back propagation neural network was trained to categorize spectra by chemical families and the network was successfully tested using familiar and unfamiliar chemicals. Performance of the network was associated with a region of the spectrum associated with fragment ions which could be extracted from spectra and were class specific. PMID- 17723721 TI - Analysis of arsenic and calcium in soil samples by laser ablation mass spectrometry. AB - We present an analytical procedure based on laser ablation mass spectrometry (LAMS) in order to detect and quantify arsenic and calcium in soil samples and we analyze the diverse factors that influence the precision of LAMS, such as laser fluence and matrix effect. The results indicate that a Zn matrix is a good choice for the analysis of those metals in soil samples. This work also provides a method for the direct determination of As in soil samples whose concentrations are lower than 100 ppm with a 70 ppm minimum detection limits (MDL). PMID- 17723722 TI - Univariate near infrared methods for determination of pesticides in agrochemicals. AB - It has been developed a general strategy for the determination of pesticides in agrochemicals by Fourier transform near infrared (FT-NIR) spectroscopy. The methodology is based on previous extraction of the active principles through sonication with acetonitrile and direct determination by transmission measurements, using glass vials as measurement cells and univariate calibration at selected wavenumbers as a function of the pesticide to be analyzed. Chlorsulfuron, metamitron, iprodione, pirimicarb, procymidone and tricyclazole were used as test molecules and data obtained by FT-NIR for 20 samples containing one of these active principles compare well with those found by reference liquid chromatography (HPLC) procedures. In short, FT-NIR provides relative standard deviations between 0.04 and 0.7% and limit of detection values ranging from 0.004 to 0.17 mg g(-1) with recovery values between 96.4 and 100.5%. On the other hand, FT-NIR offers a 10 times faster methodology than chromatography ones and an environmentally friendly alternative which reduces the reagent consumption to 1 mL acetonitrile per sample. PMID- 17723723 TI - Least-squares support vector machines and near infrared spectroscopy for quantification of common adulterants in powdered milk. AB - This paper proposes the use of the least-squares support vector machine (LS-SVM) as an alternative multivariate calibration method for the simultaneous quantification of some common adulterants (starch, whey or sucrose) found in powdered milk samples, using near-infrared spectroscopy with direct measurements by diffuse reflectance. Due to the spectral differences of the three adulterants a nonlinear behavior is present when all groups of adulterants are in the same data set, making the use of linear methods such as partial least squares regression (PLSR) difficult. Excellent models were built using LS-SVM, with low prediction errors and superior performance in relation to PLSR. These results show it possible to built robust models to quantify some common adulterants in powdered milk using near-infrared spectroscopy and LS-SVM as a nonlinear multivariate calibration procedure. PMID- 17723724 TI - A membraneless gas diffusion unit: design and its application to determination of ethanol in liquors by spectrophotometric flow injection. AB - This work presents new design of a gas diffusion unit, called 'membraneless gas diffusion (MGD) unit', which, unlike a conventional gas diffusion (GD) unit, allows selective detection of volatile compounds to be made without the need of a hydrophobic membrane. A flow injection method was developed employing the MGD unit to determine ethanol in alcoholic drinks based on the reduction of dichromate by ethanol vapor. Results clearly demonstrated that the MGD unit was suitable for determination of ethanol in beer, wine and distilled liquors. Detection limit (3S/N) of MGD unit was lower than the GD unit (GD: 0.68%, v/v; MGD: 0.27%, v/v). The MGD design makes the system more sensitive as mass transfer is more efficient than that of GD and thus, MGD can perfectly replace membrane based designs. PMID- 17723726 TI - Determination of trace impurities in high-purity zirconium dioxide by inductively coupled plasma atomic emission spectrometry using microwave-assisted digestion and wavelet transform-based correction procedure. AB - This paper describes a rapid, accurate and precise method for the determination of trace Fe, Hf, Mn, Na, Si and Ti in high-purity zirconium dioxide (ZrO2) powders by inductively coupled plasma atomic emission spectrometry (ICP-AES). The samples were dissolved by a microwave-assisted digestion system. Four different digestion programs with various reagents were tested. It was found that using a mixture of sulfuric acid (H2SO4) and ammonium sulfate ((NH4)2SO4), the total sample dissolution time was 30 min, much shorter than that required for conventional digestion in an opening system. The determination of almost all of the target analytes suffered from spectral interferences, since Zr shows a line rich atomic emission spectrometry. The wavelet transform (WT), a recently developed mathematical technique was applied to the correction of spectral interference, and more accurate and precise results were obtained, compared with traditional off-peak background correction procedure. Experimental work revealed that a high Zr concentration would result in a significant decrease in peak height of the analyte lines, which was corrected by standard addition method. The performance of the developed method was evaluated by using synthetic samples. The recoveries were in the range of 87-112% and relative standard deviation was within 1.1-3.4%. The detection limits (3sigma) for Fe, Hf, Mn, Na, Si and Ti were found to be 1.2, 13.3, 1.0, 4.5, 5.8 and 2.0 microg g(-1), respectively. The results showed that with the microwave-assisted digestion and the WT correction, the detection limits have improved by a factor of about 5 for Fe, 4 for Mn and Ti, 3 for Si, and 2 for Hf and Na, respectively, in comparison with conventional open-system digestion and off-peak correction. The proposed technique was applied to the analysis of trace elements above-mentioned in three types of ZrO2 powders. PMID- 17723725 TI - Determination of hydrogen sulfide and volatile thiols in air samples by mercury probe derivatization coupled with liquid chromatography-atomic fluorescence spectrometry. AB - A new procedure is proposed for the sampling and storage of hydrogen sulphide (H2S) and volatile thiols (methanethiol or methyl mercaptan, ethanethiol and propanethiol) for their determination by liquid chromatography. The sampling procedure is based on the trapping/pre-concentration of the analytes in alkaline aqueous solution containing an organic mercurial probe p-hydroxymercurybenzoate, HO-Hg-C6H4-COO- (PHMB), where they are derivatized to stable PHMB complexes based on mercury-sulfur covalent bonds. PHMB complexes are separated on a C18 reverse phase column, allowing their determination by liquid chromatography coupled with sequential non-selective UV-vis (DAD) and mercury specific (chemical vapor generation atomic fluorescence spectrometry, CVGAFS) on-line detectors. PHMB complexes, S(PHMB)2CH3S-PHMB, C2H5S-PHMB and C3H7S-PHMB, are stable alt least for 12 h at room temperature and for 3 months if stored frozen (-20 degrees C). The best analytical figures of merits in the optimized conditions were obtained by CVGAFS detection, with detection limits (LODc) of 9.7 microg L(-1) for H2S, 13.7 microg L(-1) for CH(3)SH, 17.7 microg L(-1) for C2H5SH and 21.7 microg L(-1) for C3H7SH in the trapping solution in form of RS-PHMB complexes, the relative standard deviation (R.S.D.) ranging between 1.0 and 1.5%, and a linear dynamic range (LDR) between 10 and 9700 microg L(-1). Conventional UV absorbance detectors tuned at 254 nm can be employed as well with comparable R.S.D. and LDR, but with LODc one order of magnitude higher than AFS detector and lower specificity. The sampling procedure followed by LC-DAD-CVGAFS analysis has been validated, as example, for H2S determination by a certified gas permeation tube as a source of 3.071+/-0.154 microg min(-1) of H2S, giving a recovery of 99.8+/ 7% and it has been applied to the determination of sulfur compounds in real gas samples (biogas and the air of a plant for fractional distillation of crude oil). PMID- 17723727 TI - Development and validation of a new analytical method for the determination of 1,4-dichlorobenzene in honey by gas chromatography-isotope dilution mass spectrometry after steam-distillation. AB - A simple, fast, sensitive and robust analytical method using gas chromatography (GC)-isotope dilution mass spectrometry (MS) was developed and validated for the identification and quantification of 1,4-dichlorobenzene (p-DCB) residues in honey samples. The proposed methodology is based on steam-distillation using a Clevenger-type apparatus followed by gas chromatography-mass spectrometry (GC-MS) in the selected ion monitoring (SIM) mode employing the isotopically labeled analogue d4-1,4-dichlorobenzene (d4-p-DCB) as internal standard (IS). Validation of the method was performed in two different GC-MS systems, using quadrupole MS (QMS) and ion-trap MS (ITMS) detectors, with no statistically significant differences between two. Recoveries were better than 91% with percent relative standard deviations lower than 12%. The instrumental limits of detection were 1 microg kg(-1) in the GC-ITMS system and 0.6 microg kg(-1) in the GC-QMS system. The expanded uncertainty was estimated as 17% at the currently accepted "action level" of 10 microg kg(-1). The method was applied to the analysis of 310 honey samples in an extensive national monitoring study. A quality control (QC) system applied during the assays has demonstrated a good performance and long-term stability over a period of more than 8 months of continuous operation. PMID- 17723728 TI - Homogeneous chemiluminescent assays for free choline in human plasma and whole blood. AB - Choline was oxidized in the presence of choline oxidase and the hydrogen peroxide generated was detected using a chemiluminescent acridinium-9-carboxamide. The dose response for choline (0-150 microM) was established in buffer and was validated for the quantification of choline in human plasma and whole blood. This homogeneous assay was performed in a 96-well microplate format and required minimal sample volume (4 microL) and short analysis time (<5s per well). The new assay(s) correlated well (R>0.98, plasma; R>0.97, whole blood) with LC-MS/MS. PMID- 17723729 TI - Synthesis of salicylaldehyde-modified mesoporous silica and its application as a new sorbent for separation, preconcentration and determination of uranium by inductively coupled plasma atomic emission spectrometry. AB - A new functionalized mesoporous silica (MCM-41) using salicylaldehyde was utilized for the separation, preconcentration and determination of uranium in natural water by inductively coupled plasma atomic emission spectrometry (ICP AES). Experimental conditions for effective adsorption of trace levels of U(VI) were optimized. The preconcentration factor was 100 (1.0 mL of elution for a 100 mL sample volume). The analytical curve was linear in the range 2-1000 microg L( 1) and the detection limit was 0.5 ng mL(-1). The relative standard deviation (R.S.D.) under optimum conditions was 2.5% (n=10). Common coexisting ions did not interfere with the separation and determination of uranium at pH 5. The sorbent exhibited excellent stability and its sorption capacity under optimum conditions has been found to be 10mg of uranium per gram of sorbent. The method was applied for the recovery and determination of uranium in different water samples. PMID- 17723730 TI - Creation of recognition sites for organophosphate esters based on charge transfer and ligand exchange imprinting methods. AB - This manuscript describes a method for the selective binding behavior of paraoxan and parathion compounds on surface imprinted polymers which were prepared using both charge transfer (CT) (methacryloyl-antipyrine, MAAP) and ligand-exchange (LE) (methacryloyl-antipyrine-gadalonium, MAAP-Gd) monomers. These polymers were prepared in the presence of azobisisobutyronitrile (AIBN) as an initiator and crosslinking EDMA and were imprinted with organophosphate esters. Influence of CT and LE imprinting on the creation of recognition sites toward paraoxan and parathion was determined applying adsorption isotherms. The effect of initial concentration of paraoxan and parathion, adsorption time and imprinting efficiency on adsorption selectivity for MIP-CT and MIP-LE was investigated. Association constant (K(ass)), number of accessible sites (Q(max)), relative selectivity coefficient (k') and binding ability were also evaluated. PMID- 17723731 TI - Montmorillonite as an adsorbent for extraction and concentration of atrazine, propazine, deethylatrazine, deisopropylatrazine and hydroxyatrazine. AB - Adsorption properties of the clay mineral montmorillonite in the potassium homoionic form (KMT) was investigated to achieve the extraction and concentration of the herbicides atrazine (AT) and propazine (PROP), as well as the main degradation products of atrazine, namely deethylatrazine (DEA), deisopropylatrazine (DIA) and hydroxyatrazine (ATOH). A batch approach was proposed, with recovery percentages for AT, PROP and DIA higher than 90% at concentrations of 0.50 and 2.50 microg L(-1). For DEA and ATOH, however, low recoveries were obtained. For DEA, this fact can be explained by its low K(d) with KMT, contrary to ATOH, which interacts strongly with the mineral surface, hindering the complete desorption and hence, generating low recovery percentages. The influence of pH, ionic strength and humic acid was studied, and a comparison with the C(18) phase as SPE cartridges was carried out. Montmorillonite showed a similar performance to commercial cartridge for concentrations of AT, DEA and PROP, but better recoveries for DIA was obtained using the clay mineral. For ATOH the recovery was also higher on the clay mineral, although for this compound the most suitable SPE cartridge is constituted by cation exchange resin. After the concentration and elution steps, the 0.50 and 2.50 microg L(-1) gave chromatographic peak areas that could be easily quantified with an analytical curve obtained in the concentration range between 7.5 and 100 microg L(-1). The obtained concentration factors are suitable to allow the application of the method to the monitoring of triazine residues in drinking water. PMID- 17723732 TI - Optimization of microwave-assisted solvent extraction for volatile organic acids in tobacco and its comparison with conventional extraction methods. AB - In the present study, a new method using microwave-assisted solvent extraction (MASE) technique followed directly GC analysis was developed for the extraction of volatile organic acids (VOAs) in tobacco. The MASE conditions (heating time, volume of extracting solvent and extraction temperature) were optimized by means of an orthogonal array design (OAD) procedure. The results suggested that extractant, temperature and heating time were statistically the most significant factors. The extracts were directly analyzed with capillary GC operating in splitless-injection mode on an Agilent HP-FFAP capillary column. Under optimum operating conditions, MASE showed significantly better recoveries than those obtained by the conventional extraction method (ultrasonic and reflux extraction), ranging from 90.6% to 103.2%. In addition, a drastic reduction of the extraction time (20 min versus 4h) and solvent consumption (20 mL versus 100 mL) was achieved with an outstanding reproducibility (CV < or =5%). PMID- 17723733 TI - Monitoring of bentonite pore water with a probe based on solid-state microsensors. AB - Repositories for the disposal of radioactive waste generally rely on a multi barrier system to isolate the waste from the biosphere. This multi-barrier system typically comprises the natural geological barrier provided by the repository host rock and its surroundings and an engineered barrier system (EBS). Bentonite is being studied as an appropriated porous material for an EBS to prevent or delay the release and transport of radionuclides towards biosphere. The study of pore water chemistry within bentonite barriers will permit to understand the transport phenomena of radionuclides and obtain a database of the bentonite-water interaction processes. In this work, the measurement of some chemical parameters in bentonite pore water using solid-state microsensors is proposed. Those sensors are well suited for this application since in situ measurements are feasible and they are robust enough for the long periods of time that monitoring is needed in an EBS. A probe containing an ISFET (ion sensitive field effect transistor) for measuring pH, and platinum microelectrodes for measuring conductivity and redox potential was developed, together with the required instrumentation, to study the chemical changes in a test cell with compacted bentonite. Response features of the sensors' probe and instrumentation performance in synthetic samples with compositions similar to those present in bentonite barriers are reported. Measurements of sensors stability in a test cell are also presented. PMID- 17723734 TI - Potentiometric membrane sensor based on 6-(4-nitrophenyl)-2,4-diphenyl-3,5-diaza bicyclo[3.1.0]hex-2-ene for detection of Sn(II) in real samples. AB - A Sn2+ ion-selective electrode which was prepared with a polymeric membrane based on 6-(4-nitrophenyl)-2,4-diphenyl-3,5-diaza-bicyclo[3.1.0]hex-2-ene (NDDBH) as a ionophore. Effects of experimental parameters such as membrane composition, nature and amount of plasticizer, the amount of additive and concentration of internal solution on the potential response of Sn2+ sensor were investigated. The electrode exhibited a Nernstian slope of 28.8+/-1.1 mV/decade of Sn2+ over a concentration range of 1.0 x 10(-5) to 1.0 x 10(-1) M of Sn2+ in an acidic solution (pH 1). The limit of detection was 4.0 x 10(-6) M. The results show that this electrode can be used in ethanol media until 20% (v/v) concentration without interference. It can be used for more than 6 weeks without any considerable divergence in the potentials. The proposed membrane electrode revealed very good selectivity for Sn(II) ions over a wide variety of other cations and could be used in acidic media. The standard electrode potentials were determined at different temperatures and used to calculate the isothermal coefficient of the electrode. The stability constant (log K(s)) of the Sn(II)-ionophore complex was determined at 25 degrees C by potentiometric titration in mixed aqueous solution. It was used as indicator electrode in potentiometric determination of Sn(II) ion in real samples. PMID- 17723735 TI - Simultaneous amperometric determination of lignin peroxidase and manganese peroxidase activities in compost bioremediation using artificial neural networks. AB - The activities of lignin-degrading peroxidases are the primary decomposition indexes in compost bioremediation. In this paper, artificial neural networks (ANNs) have been combined with an enzyme sensor for simultaneous determination of lignin peroxidase (LiP) and manganese peroxidase (MnP) activities secreted by Phanerochaete chrysosporium in composting of municipal solid waste. The LiP and MnP activities were detected through catalytic redox of H2O2, hydroquinone and veratryl alcohol as substrates by an amperometric sensor immersed in the culture filtrate solution. Due to the dynamic, nonlinear and uncertain characteristics of the complex composting system, ANNs have been used as a chemometric tool for overlapping signal deconvolution and modelling to quantify the two enzyme activities separately. Feedforward backpropagation network was used for the training process. The effects of the transfer functions, the amount of current values, the number of hidden neurons and the optimization algorithm were investigated. The LiP activities in the filtrate varied from 8.14 to 29.79 U L( 1), and from 0.36 to 1.37 U L(-1) for MnP activities. A good prediction capability was obtained, with correlation coefficients of 0.9936 for LiP activity and 0.9976 for MnP activity between the expected and predicted values of the external test samples. The performance of the ANN model was compared with the linear regression model in respect to simulation accuracy, adaptability to uncertainty, etc. All the results show that the combination of amperometric enzyme sensor and artificial neural networks is a rapid, sensitive and robust method in the quantitative study of composting system. PMID- 17723736 TI - Determination of triflumizole by differential pulse polarography in formulation, soil and natural water samples. AB - A novel electroanalytical procedure is proposed for the determination of the triflumizole in formulation, soil and natural water samples using differential pulse polarography (DPP). Triflumizole exhibited a single well-defined cathodic peak over the pH range of 1.0-9.0 in Britton-Robinson (B-R) buffers. The peak potentials were shifted to more negative values upon increasing the pH and a plot of reduction potentials (E(p)) versus pH exhibited two linear segments with a break at pH 4.0 which corresponded to the pK(a)+/-1 value of triflumizole. The peak appeared as a maximum at pH 2.0 (-810 mV versus saturated calomel electrode (SCE)) was well resolved and suitable to be investigated for analytical use. The current-concentration plot obtained using this peak was rectilinear over the range from 2.0 to 91.0 micromol L(-1) with a correlation coefficient of 0.993. The limit of detection (LOD) and limit of quantification (LOQ) were obtained as 0.72 and 2.39 micromol L(-1), respectively. The proposed method was successfully applied to the determination of triflumizole in spiked soil and lake water. The mean recoveries of the pesticide were 102.1 and 103.6% with a relative standard deviation of 1.01 and 2.68% in soil and lake water, respectively. The method was extended to the determination of triflumizole in agrochemical fungicide formulation Trifmine and results were in agreement with that obtained by high performance liquid chromatographic analysis (HPLC). The influence of some diverse ions and some other pesticides was also investigated. PMID- 17723737 TI - Models and objective functions for the optimisation of selectivity in reversed phase liquid chromatography. AB - Interpretive methodologies are the most efficient tools for finding the optimal conditions in chromatography. These methodologies are supported by models or algorithms able to infer the system behaviour upon changes in the experimental factors. Once the models are built with data obtained from sets of carefully designed experiments, molecular modelling or other approaches, they can be applied to predict the performance of new conditions. The different elements involved in these methodologies, for both isocratic and gradient elution, are given. Special attention is devoted to the description of retention, owing to its major impact on the prediction of chromatographic resolution. Several models considering the main factors affecting retention (i.e. organic modifiers, pH and temperature), and procedures that enhance the predictions, are presented. Both the existence of skewed peaks and the effect of elution conditions on peak profiles are considered. Finally, the assessment of resolution, as well as other secondary aims that affect the practical suitability of the optimal conditions, is discussed. PMID- 17723738 TI - HPLC-UV and HPLC-MSn multiresidue determination of amidosulfuron, azimsulfuron, nicosulfuron, rimsulfuron, thifensulfuron methyl, tribenuron methyl and azoxystrobin in surface waters. AB - The paper presents a new HPLC method, with UV and MS(n) detection, for the determination of seven pesticides, including the sulfonylurea herbicides amidosulfuron, azimsulfuron, nicosulfuron, rimsulfuron, thifensulfuron methyl, tribenuron methyl, and the fungicide azoxystrobin characterised by a methoxyacrilate structure. The methodology consists of a preconcentration/SPE (solid phase extraction) step and HPLC-UV (240 nm detection wavelength)-MS(n) analysis. Under the optimised conditions and after a 1000/1 preconcentration factor, the limits of detection were lower than 14.5 ng L(-1) for UV detection and lower than 8.1 ng L(-1) for MS detection. The limits of quantification were lower than 48.3 ng L(-1) in UV detection and than 26.9 ng L(-1) in MS(n) detection. The analysis of two samples, spiked with a mixture of the pesticides at threshold level concentrations, gave more than 60% recovery. PMID- 17723739 TI - 2,7-dimethyl-3,8-dinitrodipyrazolo[1,5-a:1',5'-d]pyrazine-4,9-dione: a new labelling reagent for liquid chromatographic analysis of amino acids. AB - The use of 2,7-dimethyl-3,8-dinitrodipyrazolo[1,5-a:1',5'-d]pyrazine-4,9-dione as pre-column reagent for LC analysis of amino acids is proposed. The compound reacts (30 min at 68 degrees C in presence of 0.04 M triethylamine in a dimethylsulfoxide-water mixture) with primary and secondary amino function and the stable resulting adducts can be chromatographed under reversed-phase conditions and detected at lambda=280 nm. The derivatization conditions were optimized by a series of experiments. The effect of temperature, triethylamine concentration and reagent on the reaction was investigated. The yield of the glycine derivative was found to be quantitative at a reagent amino acid molar ratio of about 6 by comparison with an authentic specimen of synthesized glycine adduct. Application of the method to quality control of commercially available oral polyaminoacid formulations is described. PMID- 17723740 TI - Proteomic profiling of human urinary proteome using nano-high performance liquid chromatography/electrospray ionization tandem mass spectrometry. AB - Urine, a blood filtrate produced by the urinary system, is an ideal bio-sample and a rich source of biomarkers for diagnostic information. Many components in urine are useful in clinical diagnosis, and urinary proteins can be strong indication for many diseases such as proteinuria, kidney, bladder and urinary tract diseases. To enhance our understanding of urinary proteome, the urine proteins were prepared by different sample cleanup preparation methods and identified by nano-high performance liquid chromatography electrospray ionization tandem mass spectrometry followed by peptide fragmentation pattern. The experimental results demonstrated that a total of 2283 peptides, corresponding to 311 unique proteins, were identified from human urine samples, in which 104 proteins with higher confidence levels. The present study was designed to establish optimal techniques to create a proteomic map of normal urinary proteins. Also, a discussion of novel approaches to urine protein cleanup and constituents is given. PMID- 17723741 TI - Determination of ethylenediaminetetraacetic acid, ethylenediaminedisuccinic acid and iminodisuccinic acid in cosmetic products by capillary electrophoresis and high performance liquid chromatography. AB - A capillary electrophoresis (CE) and a high performance liquid chromatography (HPLC) method are described for the simultaneous determination of ethylenediaminetetraacetic acid (EDTA), S,S'-ethylenediaminedisuccinic acid (EDDS) and R,S-iminodisuccinic acid (IDS) complexing agents as their Fe(III) complexes in cosmetics like shower cream and foam bath. The non-biodegradable EDTA is used in combination with biodegradable analogues like EDDS and IDS in many commercial products. The HPLC method involves separation by reversed-phase ion pair chromatography on a C(18) column using methanol-formate buffer (20 mM tetrabutylammonium hydrogen sulfate, 15 mM sodium formate adjusted to pH 4.0 with formic acid) (10:90, v/v) as mobile solvent at a flow rate of 0.8 mL min(-1) at 24 degrees C using UV detection at 240 nm. The CE separation was performed in a fused silica capillary of 50 microm i.d. with the total length of 50 cm with a 10 mM MES and MOPSO (pH 5.5) at an applied voltage of -25 kV. The samples were introduced by applying a 50 mbar pressure for 2s. Absorbances at 215 and 225 nm were monitored for the detection of the complexes. The methodology performance of the two methods was evaluated in terms of linearity, limit of detection (LOD), limit of quantitation (LOQ) and reproducibility. The LOD values obtained from HPLC are low when compared with CE. The applicability of both the methods was demonstrated for the analysis of cosmetic products such as shower cream and foam bath. The results obtained by both CE and HPLC were found to be comparable and in good agreement. PMID- 17723743 TI - Separation and determination of trace amounts of zinc, lead, cadmium and mercury in tap and Qaroun lake water using polyurethane foam functionalized with 4 hydroxytoluene and 4-hydroxyacetophenone. AB - A stable chelating sorbent was synthesized by covalently linking 4-hydroxytoluene or 4-hydroxyacetophenone with the polyurethane foam (PUF) through -N=N- group. The synthesized chelating sorbents were characterized by IR and UV/vis measurements. The modified foams show excellent stability towards various solvents. Factors influencing the extraction process of Zn(II), Pb(II), Cd(II) and Hg(II) were studied and evaluated as a function of pH of metal ion solution and equilibration shaking time. The values of sorption capacity of metal ions (microg g(-1)) were determined with the two types of bonded foams. The two phenolic bonded foams were studied comparatively. The potential applications of the two newly synthesized foams for the removal and separation of the examined metal ions from two natural water samples (drinking tap water and Qaroun lake water at Fayoum City, Egypt) were investigated. Precision (assessed as a relative standard deviation, R.S.D.) was also evaluated and found to be < or =7.3% (N=5) with a detection limit under 0.46 microg L(-1). PMID- 17723742 TI - Simultaneous separation of five fluoroquinolone antibiotics by capillary zone electrophoresis. AB - A novel methodology has been developed for simultaneous separation of ciprofloxacin (CPFLX), gatifloxacin (GTFLX), levofloxacin (LVFLX), moxifloxacin (MFLX) and sparfloxacin (SPFLX) fluoroquinolone antibiotics (FQs), using capillary zone electrophoresis (CZE) with UV detection at 282 nm. Electrolyte composition was optimized through the variation of the Tris/hydrochloride and sodium tetraborate buffer mixture. The electrolyte consisted of a 25 mmol L(-1) Tris/hydrochloride and 15 mmol L(-1) sodium tetraborate buffer mixture resulting in pH 8.87. All analytes were separated in less than 3 min. The proposed method was applied to the separation of FQs in pharmaceutical formulations, and the assay results were within 95-105% of the label claim. PMID- 17723744 TI - Simultaneous quantification of 17 trace elements in blood by dynamic reaction cell inductively coupled plasma mass spectrometry (DRC-ICP-MS) equipped with a high-efficiency sample introduction system. AB - A quadrupole inductively coupled plasma mass spectrometer (Q-ICP-MS) equipped with a dynamic reaction cell (DRC) and coupled with a desolvating nebulization system (APEX-IR) was employed to determine 17 elements (Al, As, Ba, Cd, Co, Cr, Li, Mn, Mo, Ni, Pb, Sb, Se, Sn, Sr, V, and Zr) in blood samples. Ammonia (for Al, Cr, Mn, and V) and O2 (for As and Se) were used as reacting gases. Selection of the best flow rate of the gases and optimization of the quadrupole dynamic bandpass tuning parameter (RPq) were carried out, using digested blood diluted 1+9 with deionized water and spiked with 1 microg L(-1) of Al, Cr, Mn, V and 5 microgL(-1) of As and Se. Detection limits were determined in digested blood using the 3sigma criterion. The desolvating system allowed a sufficient sensitivity to be achieved to determine elements at levels of ng L(-1) without detriment of signal stability. The accuracy of the method was tested with the whole blood certified reference material (CRM), certified for Al, As, Cd, Co, Cr, Mn, Mo, Ni, Pb, Sb, Se, and V, and with indicative values for Ba, Li, Sn, Sr, and Zr. The addition calibration approach was chosen for analysis. In order to confirm the DRC data, samples were also analyzed by means of sector field inductively coupled plasma mass spectrometry (SF-ICP-MS), operating in medium (m/Deltam=4000) and high (m/Deltam=10,000) resolution mode and achieving a good agreement between the two techniques. PMID- 17723745 TI - New reliable Raman collection system using the wide area illumination (WAI) scheme combined with the synchronous intensity correction standard for the analysis of pharmaceutical tablets. AB - A novel and reliable Raman collection system for the non-destructive analysis of pharmaceutical tablets has been proposed. The main idea was to develop and utilize the wide area illumination (WAI) scheme for Raman collection to cover a large surface area (coverage area: 28.3mm2) of solid tablet to dramatically improve the reliability in sample representation and the reproducibility of sampling due to less sensitivity of sample placement with regard to the focal plane. Simultaneously, the effective and synchronous standard configuration using isobutyric anhydride was harmonized with the WAI scheme to correct the problematic variation of Raman intensity from the change of laser power. To verify the quantitative performance of the proposed scheme, the compositional analysis of active ingredient in naproxen tablet has been performed. The average sample composition was successfully represented by using the WAI scheme compared to the conventional scheme with a much smaller illumination area. After the intensity correction using the non-overlapping peak of isobutyric anhydride standard and area normalization, a partial least squares (PLS) model was developed using an optimized spectral range and the concentrations of naproxen in tablets were accurately predicted. The prediction accuracy was not sensitive to changes in laser power or tablet position within +/-2mm. Additionally, the prediction accuracy was repeatable without systematic drift or need for re calibration. PMID- 17723746 TI - Automatic identification of terpenoid skeletons by feed-forward neural networks. AB - Feed-forward neural networks (FFNNs) were used to predict the skeletal type of molecules belonging to six classes of terpenoids. A database that contains the 13C NMR spectra of about 5000 compounds was used to train the FFNNs. An efficient representation of the spectra was designed and the constitution of the best FFNN input vector format resorted from an heuristic approach. The latter was derived from general considerations on terpenoid structures. PMID- 17723747 TI - Voltammetric studies on the electrochemical determination of methylmercury in chloride medium at carbon microelectrodes. AB - Electroanalytical techniques have been used to determine methylmercury at low levels in environmental matrices. The electrochemical behaviour of methylmercury at carbon microelectrodes in a hydrochloric acid medium using cyclic, square wave and fast-scan linear-sweep voltammetric techniques has been investigated. The analytical utility of the methylmercury reoxidation peak has been explored, but the recorded peak currents were found to be poorly reproducible. This is ascribed to two factors: the adsorption of insoluble chloromercury compounds on the electrode surface, which appears to be an important contribution to hinder the voltammetric signal of methylmercury; and the competition between the reoxidation of the methylmercury radical and its dimerization reaction, which limits the reproducibility of the methylmercury peak. These problems were successfully overcome by adopting the appropriate experimental conditions. Fast-scan rates were employed and an efficient electrochemical regeneration procedure of the electrode surface was achieved, under potentiostatic conditions in a mercury-free solution containing potassium thiocyanate--a strong complexing agent. The influence of chloride ion concentration was analysed. Interference by metals, such as lead and cadmium, was considered. Calibration plots were obtained in the micromolar and submicromolar concentration ranges, allowing the electrochemical determination of methylmercury in trace amounts. An estuarine water sample was analysed using the new method with a glassy carbon microelectrode. PMID- 17723748 TI - A rapid and sensitive chemiluminescence enzyme-linked immunosorbent assay for the determination of fumonisin B1 in food samples. AB - An enzyme-linked immunosorbent assay (ELISA) based on polyclonal antibody with enhanced chemiluminescent (ECL) detection of fumonisin B1 (FB1) in food samples has been developed. Assay conditions, including concentrations of antibody and enzyme conjugate, competition time and so on, were optimized. The effects of pH and two different organic solvents were investigated. The optimized ECL-ELISA system allowed FB1 determination in a linear working range of 0.14-0.9 microg L( 1) with IC50 value of 0.32 microg L(-1) and a limit of detection of 0.09 microg L(-1). The ECL-ELISA was about 10 times more sensitive and about 30% time less than that of colorimetric ELISA using the same antibody and HRP-conjugate. Good recoveries with spiked food samples were obtained, and the results correlated well with those obtained using conventional direct competition ELISA assay and HPLC method, which indicated that ECL-ELISA was capable of being applied for the specific detection and routine monitoring of FB1 in food samples. PMID- 17723749 TI - Flow-injection post chemiluminescence determination of atropine sulfate. AB - A new post chemiluminescence (PCL) reaction was observed when atropine sulfate was injected into the reaction mixture after the finish of CL reaction of Ce(IV) and sodium sulfite. The possible mechanism for the PCL reaction was discussed via the investigation of the CL kinetic characteristics, the CL spectra, the UV absorption spectra and the fluorescence spectra of some related substances. The flow injection PCL method for the determination of atropine sulfate was established. The relative standard deviation (R.S.D.) was 2.8% (n=11, c=5.0 x 10( 6)g mL(-1)). The PCL intensity responded linearly to the concentration of atropine sulfate in the range 1.0 x 10(-6) to 5.0 x 10(-5)g mL(-1) with a linear correlation of 0.9947. The detection limit was 4 x 10(-7)g mL(-1) atropine sulfate. The method had been applied to the determination of atropine sulfate in the tablets and the results were consistent with the method of Chinese pharmacopoeia. PMID- 17723750 TI - Sensors based on galvanic cell generated electrochemiluminescence and its application. AB - In this paper, a novel electrochemiluminescence (ECL) imaging sensor array was developed for determination of hydrogen peroxide (H2O2), which was based on Cu/Zn alloy galvanic cell generated ECL. In alkaline solution, Cu/Zn galvanic cell was formed because of corrosion effect, the galvanic cell could supply stable potential for ECL generation of luminol, and the weak ECL emission could be enhanced by H(2)O(2). The galvanic cell sensor array was designed by putting Cu/Zn alloy in 96-well microtiter plates separately. The relative ECL intensity was proportional with the concentration of hydrogen peroxide in the range of 1.0 x 10(-6) to 1.0 x 10(-4) mol l(-1) and the detection limit was 3.0 x 10(-7) mol l(-1) (3sigma), the relative standard deviation (R.S.D.) for 11 parallel measurements of 1.0 x 10(-5)mol l(-1) H2O2 was 4.0%. PMID- 17723751 TI - A flow cytometric assay technology based on quantum dots-encoded beads. AB - A flow cytometric detecting technology based on quantum dots (QDs)-encoded beads has been described. Using this technology, several QDs-encoded beads with different code were identified effectively, and the target molecule (DNA sequence) in solution was also detected accurately by coupling to its complementary sequence probed on QDs-encoded beads through DNA hybridization assay. The resolution of this technology for encoded beads is resulted from two longer wavelength fluorescence identification signals (yellow and red fluorescent signals of QDs), and the third shorter wavelength fluorescence signal (green reporting signal of fluorescein isothiocyanate (FITC)) for the determination of reaction between probe and target. In experiment, because of QDs' unique optical character, only one excitation light source was needed to excite the QDs and probe dye FITC synchronously comparing with other flow cytometric assay technology. The results show that this technology has present excellent repeatability and good accuracy. It will become a promising multiple assay platform in various application fields after further improvement. PMID- 17723752 TI - Anodic stripping voltammetry at in situ bismuth-plated carbon and gold microdisc electrodes in variable electrolyte content unstirred solutions. AB - Carbon and gold microdisc electrodes (30 and 10 microm, respectively) have been tested as substrates for in situ bismuth film plating from unstirred solutions of variable acetate buffer content and were subsequently used in the anodic stripping voltammetry determination of Pb(II) and Cd(II) ions. The effects of Bi(III) concentration, analyte accumulation time, stirring as well as supporting electrolyte content have been studied. Under optimal conditions good voltammetric responses were obtained by means of square wave anodic stripping voltammetry in unstirred analyte solutions of 5 x 10(-8) to 10(-6)M, even in the absence of added buffer. In an indicative application, Pb(II) ion levels were determined in tap water using bismuth-plated carbon microdisc electrodes. PMID- 17723753 TI - Determination of picomolar levels of platinum in estuarine waters: a comparison of cathodic stripping voltammetry and isotope dilution-inductively coupled plasma mass spectrometry. AB - A comparative study to determine picomolar concentrations of platinum in natural waters was performed using two different analytical techniques. Results obtained by cathodic stripping voltammetry (CSV) were compared with those obtained by isotope dilution-inductively coupled plasma mass spectrometry (ID-ICPMS) combined with anion exchange resin column extraction method. Using successive UV irradiations with low-pressure mercury (L-Hg) lamp for 4h prior to CSV analysis, the results of both methods were comparable. Without adequate photolytic decomposition, the results obtained using CSV were generally lower than those obtained using ID-ICPMS in the estuarine waters around Tokyo Bay. This difference implies the presence of organically complexed Pt species in the estuarine waters. The Pt enrichment in the middle of the Tokyo Bay estuaries probably reflects the anthropogenic release of Pt from highly populated areas in Tokyo. PMID- 17723754 TI - New spectrofluorometric application for the determination of ternary mixtures of drugs. AB - A new spectrofluorometric method was developed for the determination of a ternary mixture of dexamethasone, dexchlorpheniramine maleate, and fluphenazine hydrochloride in dosage forms where the literature did not reveal any method for analysis of this mixture. The method was based on the use of the first and second derivatives of the ratio of the emission spectra with a zero-crossing technique. The ratio spectra were obtained by dividing the emission spectrum of the mixture by that of one of the components. The concentrations of the other components were then determined from their respective calibration graphs treated similarly. The method can resolve the spectral overlapping of the three components and was applied successfully for the determination of these drugs in synthetic mixtures and in commercial dosage forms. PMID- 17723755 TI - Raman spectroscopic and structural investigation of 1,4-diphenylbuta-1,3-diene and selected monomethyl and dimethyl substituted homologues. AB - The Raman and mass spectra of 1,4-diphenylbuta-1,3-diene and several of its monomethyl and dimethyl homologues are reported and discussed, with a view to developing a spectroscopic protocol for detecting the presence and position of a methyl group in these compounds. Raman spectroscopy and mass spectrometry are shown to provide complementary information, by which the four available monomethyl homologues may be readily distinguished from each other and 1,4 diphenylbuta-1,3-diene itself. The utility of these 1,4-diarylbutadienes as model compounds for carotenoids and related materials, which may serve as indicators of extinct or extant extraterrestrial life, is considered. PMID- 17723756 TI - Surfactant-sensitized malachite green method for trace determination of orthophosphate in aqueous solution. AB - A surfactant-sensitized spectrophotometric method for determination of trace orthophosphate has been developed using anion surfactant (Ultrawet 60 L) with molybdate and malachite green in low acidic medium (pH(T) 1.0). The method detection limit (3 x standard deviation of blank, n=10) was 8 nM and the calibration curve was linear over a range of 10-400 nM (r2=0.997). The molar absorptivity was 1.26 x 10(5) L mol(-1) cm(-1) at 600 nm with the background correction at 530 nm. The precision of method was 3.4% at 50 nM and 2.4% at 100 nM orthophosphate (n=10). The hydrolysis of eight organic phosphorus and polyphosphate compounds was less than 2% of the total phosphorus present (5-10 microM). This method showed less arsenate interference than previous methods, with only 3% even in the presence of orthophosphate in the samples. No interference of silicate up to 40 microM was observed. Background anions (in an order of SO4(2-)>NO3->Cl-) have greater effects than cations (Ca2+>Mg2+>Na+) on the reagent blank and the molar absorptivity of the color product. PMID- 17723757 TI - Novel oxidation reaction of prochlorperazine with bromate in the presence of synergistic activators and its application to trace determination by flow injection/spectrophotometric method. AB - A simple and fast flow injection spectrophotometric method for the determination of bromate in water samples was developed. The detection system is based on the oxidation of prochlorperazine (PCP) with bromate in strongly acidic medium. Large amounts of chloride and bromide was found, for the first time, to act as an activator, and to enhance the sensitivity for bromate detection. The oxidation product of PCP gives pink color, which can be used to monitor the reaction spectrophotometrically at 525 nm. Under the optimal conditions, the method is selective; only nitrite, chlorite and hypochlorite can interfere with the determination of bromate. The elimination of these three ions is discussed. The calibration graph for bromate determination was linear in the range of 10-130 microg L(-1) with a detection limit of 2.3 microg L(-1). The repeatability was satisfactory, with the relative standard deviation of 1.1% (25 microg L(-1), n=10). The sample throughput was 44 h(-1). The proposed method was found to be highly reliable for screening drinking waters containing bromate, which is above or below legislation limit of 10 microg L(-1). PMID- 17723758 TI - Dynamic microwave-assisted extraction coupled with on-line spectrophotometric determination of safflower yellow in Flos Carthami. AB - A rapid dynamic microwave-assisted extraction and on-line detection by spectrophotometry is proposed for the determination of safflower yellow in Flos Carthami. A high pressure and a peristaltic pump were used to deliver the solvent. A TM010 microwave resonance cavity was applied to concentrate the microwave energy and the forward power about 60 W was enough for the extraction. Other extraction conditions also were examined and optimized. In this work, the extraction process can be monitored by measuring the absorption of safflower yellow in the extract, which would be convenient for rapid optimization of the extraction process. The detection and quantification limits are 8 and 27 microg mL(-1), respectively. The within-day and between-day precision (R.S.D.) are 1.6 3.2% and 2.8-4.2%, respectively. Compared with off-line detection, the proposed method may provide more rapid measurement and is more convenient for obtaining continuous measurements. PMID- 17723759 TI - Spectrophotometric determination of 4,6-dinitro-o-cresol (DNOC) in soil and lemon juice. AB - Although the use of once widely applied selective herbicide, 4,6-dinitro-o-cresol (DNOC), was cancelled by US-EPA in 1987, it is still found in soil and water due to its slow degradation in the environment. Since solid phase extraction spectrophotometry combinations are much simpler and cheaper than chromatography/MS based methods and most routine laboratories lack such sophisticated instrumentation, it is desirable to establish novel sensitive, well established, and field-applicable spectrophotometric methods for the rapid assay of DNOC in water and soil. For this purpose, two distinct spectrophotometric methods utilizing the periodate and copper(II)-neocuproine (Nc) reagents have been developed following Zn/HCl reduction of the pesticide in a microwave oven for 15s, and validated for DNOC determination at mg L(-1) level. The LOD values were 1.6 and 0.2 mg L(-1) for periodate and Cu(II)-Nc methods, respectively. Statistical comparison of the developed methods was made with the aid of high performance liquid chromatography (HPLC) equipped with a C18 (5 microm), 250 mm x 4.6 mm ID reversed phase column in conjunction with a UV (264 nm) detector, and a methanol (HPLC grade) +0.1% glacial acetic acid mixture mobile phase. Both spectrophotometric methods were directly applicable to soil since they were not interfered with common soil cations and anions, together with some pesticides. These methods were applied to real samples such as synthetically contaminated montmorillonite and lemon juice, and overall recovery efficiencies at the order of 95% or greater were achieved in the devised adsorption/elution procedures. An 8-hydroxyquinoline (oxine)-impregnated XAD copolymer resin stabilized with Fe(III) salt was used to preconcentrate DNOC at a concentration factor of 20 from lemon juice contaminated with 1 mg L(-1) DNOC, and the analyte retained at pH 2.5 was eluted with 0.025 M methanolic NaOH. Both the devised spectrophotometric methods and the proposed preconcentration column with optimized sorption and desorption conditions are novel for DNOC assay in the natural environment. PMID- 17723760 TI - Separation of chelating agents as copper complexes by capillary zone electrophoresis using quaternary ammonium bromides as additives in N methylformamide. AB - This study presents the use of quaternary ammonium bromides as additives in N methylformamide (NMF) for the separation and quantification of chelating agents as copper complexes by capillary zone electrophoresis (CZE). The new quaternary ammonium bromides were synthesized in our laboratory and used for the first time for CZE applications performed in NMF media. The methods were developed and optimized for determination of six chelating agents (trans-1,2-diaminocyclohexane N,N,N',N'-tetraacetic acid (CDTA), diethylenetriaminepentaacetic acid (DTPA), ethylenediaminetetraacetic acid (EDTA), N-(2-hydroxyethyl)ethylenediamine-N,N',N' triacetic acid (HEDTA), nitrilotriacetic acid (NTA) and triethylenetetraaminehexaacetic acid (TTHA)) as copper complexes. Among the tested electrolyte additives in NMF media (pH(app) 10.2) dimethyldioctylammonium bromide (DMDOAB), dimethyldinonylammonium bromide (DMDNAB) and dimethyldidecylammonium bromide (DMDDAB), at a concentration of 20 mmol L(-1) improved the separation of the copper complexes. The optimized methods require only 12 min for one analysis, and the detection limits for copper complexes of DMDNAB, the best-performing additive, were < or =24 micromol L(-1). Relative standard deviations (R.S.D.) for migration times were < or =2.5, < or =2.1, < or =3.1% and for peak areas, < or =3.1, < or =3.0, < or =3.2% for DMDOAB, DMDNAB and DMDDAB used as additives, respectively. All three methods were successfully applied to the analysis of natural and wastewater samples. No matrix effects from these samples were observed. The interaction between quaternary ammonium bromides and copper complexes is discussed. PMID- 17723761 TI - Modeling of analytical peaks: peaks properties and basic peak functions. AB - The general approach to the detailed characterizing of peak properties based on the use of characteristic points on a peak contour located at the certain levels is proposed. Three basic functions of peaks have been chosen which are submitted in normalized form on height and width. The ability to characterize a peaks shape of a certain analytical series is shown by an example of series of analytical peaks of thallium obtained by stripping voltammetry at linear and step potential sweep. Also the proposed shape parameters are studied for groups of stripping voltammetry and chromatographic peaks. PMID- 17723762 TI - Tutorial on a chemical model building by least-squares non-linear regression of multiwavelength spectrophotometric pH-titration data. AB - Although the modern instrumentation enables for the increased amount of data to be delivered in shorter time, computer-assisted spectra analysis is limited by the intelligence and by the programmed logic tool applications. Proposed tutorial covers all the main steps of the data processing which involve the chemical model building, from calculating the concentration profiles and, using spectra regression, fitting the protonation constants of the chemical model to multiwavelength and multivariate data measured. Suggested diagnostics are examined to see whether the chemical model hypothesis can be accepted, as an incorrect model with false stoichiometric indices may lead to slow convergence, cyclization or divergence of the regression process minimization. Diagnostics concern the physical meaning of unknown parameters beta(qr) and epsilon(qr), physical sense of associated species concentrations, parametric correlation coefficients, goodness-of-fit tests, error analyses and spectra deconvolution, and the correct number of light-absorbing species determination. All of the benefits of spectrophotometric data analysis are demonstrated on the protonation constants of the ionizable anticancer drug 7-ethyl-10-hydroxycamptothecine, using data double checked with the SQUAD(84) and SPECFIT/32 regression programs and with factor analysis of the INDICES program. The experimental determination of protonation constants with their computational prediction based on a knowledge of chemical structures of the drug was through the combined MARVIN and PALLAS programs. If the proposed model adequately represents the data, the residuals should form a random pattern with a normal distribution N(0, s2), with the residual mean equal to zero, and the standard deviation of residuals being near to experimental noise. Examination of residual plots may be assisted by a graphical analysis of residuals, and systematic departures from randomness indicate that the model and parameter estimates are not satisfactory. PMID- 17723763 TI - Detection of trace organophosphorus vapor with a self-assembled bilayer functionalized SiO2 microcantilever piezoresistive sensor. AB - Using piezoresistive SiO2 microcantilever technology, we present an ultra sensitive chemical sensor for trace organophosphorus vapor detection. A self assembled composite layer of Cu2+/11-mercaptoundecanoic acid is modified on the surface of the sensing cantilever as a specific coating to capture P=O containing compounds. Experimental results indicate that the sensor can be quite sensitive to DMMP vapor (well known as a simulant of nerve agent). The signal-noise-limited detection resolution of the sensor is experimentally obtained as low as several parts per billion. Besides that the sensor can yield reversible and repeatable response to DMMP vapor, adsorption of DMMP on the self-assembled composite layer is well fit to the Langmuir isotherm model. PMID- 17723764 TI - Flow-injection immuno-bioassay for interleukin-6 in humans based on gold nanoparticles modified screen-printed graphite electrodes. AB - A flow-injection electrochemical immunoassay system based on a disposable immunosensor for the determination of interleukin-6 (IL-6) was proposed. The immunosensor was prepared by entrapping horseradish peroxidase (HRP)-labeled IL-6 antibody into gold nanoparticles-modified composite membrane at a screen-printed graphite electrode. With a non-competitive immunoassay format, the immunosensor was inserted in the flow system with an injection of sample, and the injected sample containing IL-6 antigen was produced transparent immunoaffinity reaction with the immobilized HRP-labeled IL-6 antibody. The formed antigen-antibody complex inhibited partly the active center of HRP, and decreased the immobilized HRP to H2O2 reduction. The performance and factors influencing the performance of the immunosensor were investigated. Under optimal conditions, the current change obtained from the labeled HRP relative to thionine-H2O2 system was proportional to the IL-6 concentration in the range of 5-100 ng L(-1) with a detection limit of 1.0 ng L(-1) (at 3delta). The flow-injection immunoassay system could automatically control the incubation, washing and measurement steps with acceptable reproducibility and good stability. Moreover, the proposed immunosensors were used to analyze IL-6 in human serum specimens. Analytical results of clinical samples show the developed immunoassay has a promising alternative approach for detecting IL-6 in the clinical diagnosis. PMID- 17723765 TI - Penicillamine determination using a tyrosinase micro-rotating biosensor. AB - Tyrosinase [EC 1.14.18.1], immobilized on a rotating disk, catalyzed the oxidation of catechols to o-benzoquinone, whose back electrochemical reduction was detected on glassy carbon electrode surface at -150mV versus Ag/AgCl/NaCl 3M. Thus, when penicillamine (PA) was added to the solution, this thiol-containing compound participate in Michael type addition reactions with o-benzoquinone to form the corresponding thioquinone derivatives, decreasing the reduction current obtained proportionally to the increase of its concentration. This method could be used for sensitive determination of PA in drug and human synthetic serum samples. A linear range of 0.02-80 microM (r=0.999) was obtained for amperometric determination of PA in buffered pH 7.0 solutions (0.1 M phosphate buffer). The biosensor has a reasonable reproducibility (R.S.D.<4.0%) and a very stable amperometric response toward this compound (more than 1 month). PMID- 17723766 TI - A fluorescent chemosensor for cobalt ions based on a multi-substituted phenol ruthenium(II) tris(bipyridine) complex. AB - An amide-linked 2,6-bis{[(2-hydroxy-5-tert-butylbenzyl)(pyridyl-2-methyl)-amino] methyl}-4-methylphenol-ruthenium(II) tris(bipyridine) 2PF6- complex, 1, was first used to recognize Co(II) in EtOH/H(2)O (1:1, v/v) solution, with the ruthenium(II) tris(bipyridine) moiety selected as a fluorophore and the multi substituted phenol unit chosen as a receptor. The fluorescence quenching of 1 was attributed to the formation of an inclusion complex between multi-substituted phenol unit and Co(II) by 1:1 complex ratio (K=2.5 x 10(5)), which has been utilized as the basis of the fabrication of the Co(II)-sensitive fluorescent chemosensor. The analytical performance characteristics of the proposed Co(II) sensitive chemosensor were investigated. The sensor can be applied to the quantification of Co(II) with a linear range covering from 1.0 x 10(-7) to 5.0 x 10(-5) M and a detection limit of 5 x 10(-8) M. The experiment results show that the response behavior of 1 to Co(II) is pH-independent in medium condition (pH 4.5-9.5) and show excellent selectivity for Co(II) over transition metal cations except Cu(II). The chemosensor has been used for determination of Co(II) in water samples. PMID- 17723767 TI - Chemiluminescence optosensing implemented with multicommutation: determination of salicylic acid. AB - In this paper we have coupled, for the first time, chemiluminescent detection with multicommuted optosensing principles. This approach has been implemented with the use of a commercial flow cell of 1mm optical path length filled with an appropriate anionic exchanger gel as chemiluminescence sensing phase. The cell was placed in front of the window of the photosensor module of a home-made luminometer developed in our laboratory and a flat mirror was stuck on the back of the cell. The suitability of using chemiluminescence as detection technique in multicommuted flow-through optosensors has been demonstrated: the determination of salicylic acid by simple oxidation with permanganate on the sensing solid phase was chosen as model reaction. The proposed system allows the determination of salicylic acid in pharmaceuticals, with a sample frequency as high as even 60 samples h(-1) and showing a detection limit of 0.30 microg mL(-1), the linear response range is 1-30 microg mL(-1) and the R.S.D. is 3.1%. Satisfactory results have been obtained when applying the sensor to pharmaceuticals. The accuracy of the proposed methodology has been tested by using a reference method. PMID- 17723768 TI - Detection of carbamic and organophosphorous pesticides in water samples using a cholinesterase biosensor based on Prussian Blue-modified screen-printed electrode. AB - In the present paper, a comparative study using Co-phthalocyanine and Prussian Blue-modified screen-printed electrodes, has been performed. Both the electrodes have demonstrated an easiness of preparation together with high sensitivity towards thicoholine (LOD=5 x 10(-7) and 5 x 10(-6) M for Co-phthalocyanine and Prussian Blue, respectively) with high potentialities for pesticide measurement. Prussian Blue-modified screen-printed electrodes were then selected for successive enzyme immobilization due to their higher operative stability demonstrated in previous works. AChE and BChE enzymes were used and inhibition effect of different pesticides was studied with both the enzymes. AChE-based biosensors have demonstrated a higher sensitivity towards aldicarb (50% inhibition with 50 ppb) and carbaryl (50% inhibition with 85 ppb) while BChE biosensors have shown a higher affinity towards paraoxon (50% inhibition with 4 ppb) and chlorpyrifos-methyl oxon (50% inhibition with 1 ppb). Real samples were also tested in order to evaluate the matrix effect and recovery values comprised between 79 and 123% were obtained. PMID- 17723769 TI - New extraction procedure to improve the determination of quinolones in poultry muscle by liquid chromatography with ultraviolet and mass spectrometric detection. AB - The present article aims to develop a new extraction procedure to improve the determination of quinolones in chicken muscle. This new determination method was validated using liquid chromatography-ultraviolet detection (LC-UV) and liquid chromatography-mass spectrometry detection (LC-MS), which has special bearing on stability studies. The results obtained by using the method were compared with the results obtained with a previous methodology. The new extraction procedure presents a sensitivity low enough to determine concentration of these drugs below the permissible maximum residue limits (MRL) in chicken muscle and is less time consuming than the previous methodology. PMID- 17723770 TI - A rapid ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometric method for the qualitative and quantitative analysis of the constituents of the flower of Trollius ledibouri Reichb. AB - A rapid ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometric (UPLC-ESI-MS/MS) method was developed for the qualitative and quantitative determination of the constituents of the flower of Trollius ledibouri Reichb. The analysis was performed on an AcQuity UPLCtrade mark BEH C18 column using gradient elution with a mobile phase of 0.1% acetic acid and acetonitrile over 20 min. A tandem quadrupole spectrometer operating in either full scan mode or in MS/MS mode for multiple reaction monitoring (MRM) was used for the qualitative and quantitative analysis of the constituents, respectively. According to the mass spectrometric fragmentation mechanism and UPLC-ESI-MS/MS data, the chemical structures of 15 constituents of the flower of T. ledibouri Reichb. were identified on-line without time-consuming isolation and four of them, 2''-O-beta-L-galactopyranosylorientin, 2''-O-beta-arabinopyranosylorientin, orientin and vitexin, were quantified. The limits of quantification of these four flavonoids were 540, 321, 515 and 220 microg g(-1) plant material, respectively. Four commercial samples from different sources were analyzed. The UPLC-ESI-MS/MS method for analyzing the constituents can be used to evaluate the quality of the flower of T. ledibouri Reichb. PMID- 17723771 TI - Synthesis of silica-based benzeneboronic acid affinity materials and application as pre-column in coupled-column high-performance liquid chromatography. AB - Three silica-based benzeneboronic acid affinity materials were synthesized by using an m-aminobenzeneboronic acid as the ligand and using three different spacer arms. Under high-pressure, three affinity pre-columns were packed with these materials and the retention of every affinity pre-column with 11 urinary nucleosides was studied. With different spacer arms of boronic acid-substituted silica materials, the absorption to vicinal alcohols (cis-diols) and stability under acidic elution conditions are of great difference. Coupled-column liquid chromatographic methods for the direct analysis of urinary nucleosides were respectively established. As a result, two of three affinity pre-columns showed good chromatographic property in the on-line analysis of urinary nucleosides. The coupled-column system including pre-column I is the best with excellent linearity (R2>0.995), good recoveries (85.6-96.9%) and reproducibility (R.S.D.: 1.01 4.02%). The pre-column I could at least endure 150 repetitive injections of a 100 microL urinary sample. PMID- 17723772 TI - Non-aqueous capillary electrophoresis with red light emitting diode absorbance detection for the analysis of basic dyes. AB - Non-aqueous capillary electrophoresis was evaluated for the separation of five hydrophobic basic blue dyes for application in forensic dye analysis. The use of a red light emitting diode as a high intensity, low-noise light source provided sensitive detection of the blue dyes while also allowing the evaluation of solvents that absorb strongly in the UV region. Excellent peak shapes and separation selectivity were obtained in methanol, ethanol, acetonitrile and dimethylsulfoxide, however water, tetrahydrofuran, dimethylformamide and acetone were unsuitable as solvents due to poor peak shapes and a lack of sensitivity, most likely due to adsorption onto the capillary wall. Due to the known compatibility of methanol with capillary electrophoresis-mass spectrometry, this solvent was examined further with the relative acidity/basicity of the electrolyte being optimised with an artificial neural network. The optimised method was examined for the separation of ink samples from 6 fibre tip and 2 ball point blue or black pens and showed that a unique migration time for the main dye component in seven of the eight pens could be obtained. PMID- 17723773 TI - Quantitative determination of oxidized carbon nanotube probes in yeast by capillary electrophoresis with laser-induced fluorescence detection. AB - Short oxidized multi-walled carbon nanotubes were functionalized with fluorescein isothiocyanate to form carbon nanotube probes (CNTP). The distribution of CNTP in yeast was quantitatively determined by capillary electrophoresis coupled with laser-induced fluorescence detection. The detection sensitivity for CNTP was greatly improved comparing with UV absorbance and Raman detection. The time- and temperature-dependent influx patterns of CNTP into yeast were obtained. The apparent permeability coefficient for influx of CNTP into yeast was calculated, which suggested that CNTP might permeate into yeast through endocytosis. This study implies that CNTP could be a fine drug transporter and might be wildly used in multidrug resistance research and microorganism detection. PMID- 17723774 TI - Sensitive analysis of two barbiturates in human urine by capillary electrophoresis with sample stacking induced by moving reaction boundary. AB - An on-line stacking method based on moving reaction boundary (MRB) was developed for the sensitive determination of barbital and phenobarbital in human urine via capillary electrophoresis (CE). The optimized conditions for the method are: 60 mmol L(-1) pH 11.0 Gly-NaOH as the background electrolyte, 10 mmol L(-1) pH 5.5 Gly-HCl as sample buffer, secobarbital as the internal standard (IS), 12.5 kV, 1.4 psi 10s sample injection, 75 microm ID 60.2 cm total length (50 cm effective length) capillary and 214 nm detect wavelength. Under the optimized conditions, the method can well stack and separate barbital and phenobarbital in urine samples and result in 20.5-fold and 22.6-fold improvement in concentration sensitivity for barbital and phenobarbital, respectively. Furthermore, the method holds: (1) good linear calibration functions for the two target compounds (correlation coefficients r>0.999), (2) low limits of detection (0.27 microg mL( 1) for barbital and 0.26 microg mL(-1) for phenobarbital), (3) low limits of quantification (0.92 microg mL(-1) for barbital and 0.87 microg mL(-1) for phenobarbital), (4) good precision (R.S.D. of intra-day and inter-day less than 5.38% for barbital and 1.67% for phenobarbital, respectively) and (5) high recoveries at three concentration levels (90.27-106.36% for barbital and 93.05 113.60% for phenobarbital in urine). The method is simple, sensitive and efficient, and can fit to the need of clinical and forensic toxicology. PMID- 17723775 TI - Spectrofluorimetric studies on the binding of salicylic acid to bovine serum albumin using warfarin and ibuprofen as site markers with the aid of parallel factor analysis. AB - The interactions of salicylic acid (SL) and two different site markers (warfarin for site I and ibuprofen for site II) with bovine serum albumin (BSA) in pH 7.4 Tris-HCl buffer have been investigated with the use of spectrofluorimetry. An equilibrium solution of BSA and SA was titrated separately with the two markers. This initial work showed that the binding of SL with BSA could be quite complex, and that there was probably a competitive interaction occurring between ibuprofen and SL. However, the spectral results were difficult to interpret clearly for the interaction of warfarin and SL in similar circumstances. To extract more information from the resolution of fluorescence excitation-emission spectra, the contour plots of the fluorescence spectra indicated that the optimal excitation wavelengths for BSA, SL, warfarin and ibuprofen were different, and were found to be at 278, 295, 306 and 218 nm, respectively. The spectral information was arranged into three-way excitation-emission fluorescence matrix (EEM) stack arrays, and was submitted for analysis by the parallel factor analysis (PARAFAC) algorithm. Firstly, it was demonstrated that the estimated excitation and emission spectral responses for SL, BSA and the site markers, warfarin and ibuprofen, agreed well with the measured spectra. Then, the interpretation of the plots of simultaneously extracted (by PARAFAC) equilibrium concentrations for the above four reactants, showed that: (i) the SL primarily appears to bind in site I but at a different location from the high-affinity binding site (HAS) for warfarin, and the interaction partially overlaps with the low-affinity binding site (LAS) for warfarin. (ii) The SL may have two LAS-one in site II where the HAS for ibuprofen is located, and the other in site I at the LAS for ibuprofen. Thus, application of the PARAFAC method for the study of competitive interaction of SL and BSA with the aid of two different site markers has extracted information unobtainable by traditional methods such as the Scatchard plot, and provided useful means of data visualization. PMID- 17723777 TI - Comparative analysis of naphthodianthrone and phloroglucine derivatives in St. John's Wort extracts by near infrared spectroscopy, high-performance liquid chromatography and capillary electrophoresis. AB - A near infrared spectroscopic (NIRS) method is established for quantitative determination of naphthodianthrones and phloroglucine derivatives in St. John's Wort extracts. The validated NIRS method is compared with optimised liquid chromatography (LC) and capillary electrophoresis (CE), applying UV as a detection tool. Optimisation of stationary and mobile phase conditions in reversed-phase liquid chromatography (RP-LC) allow separating the derivatives of interest with high peak symmetry and robustness. Elution takes 15 and 25 min on non-porous or porous silica C18 with different porosities, respectively. Capillary electrophoresis (CE) is used for cross-validation of RP-LC. CE enables baseline separation of hypericine and pseudohypericine in less than 2min, but is ten times less sensitive. The validated RP-LC is chosen as a reference method for calibration of the NIRS-system. Analysis of 80 St. John's Wort extracts (320 NIR spectra) and the subsequent chemometric calculations of the best regression model show that NIRS is suitable for analysis of hypericine, pseudohypericine and hyperforine. RP-LC or CE must be employed for the other remaining lower concentrated naphthodianthrone and phloroglucine derivatives. Hypericine and hyperforine are analysed via NIRS with a standard error of estimation (SEE) of 0.52 and 0.50 microg mL(-1) and standard error of prediction (SEP) of 0.64 and 0.71 microg mL(-1) within few seconds. The current study demonstrates the suitability of NIRS as an alternative to LC and CE for St. John's Wort producing phytopharmaceutical industry. The short analysis time of few seconds' assures high sample throughput in routine analysis. PMID- 17723776 TI - Seafood freshness determination through vapour phase Fourier transform infrared spectroscopy. AB - A new vapour-phase manifold has been developed to determine trimethylamine (TMA) in fish and cephalopod samples by Fourier transform infrared (FT-IR) spectroscopy. Samples were treated off-line for 1h with trichloroacetic acid (TCA), filtered and washed. The obtained extracts were aspirated and alkalinized with NaOH 2.0M, in an on-line system. TMA was separated from the solution in a gas phase separator and then transported by means of a nitrogen carrier into a home made 10 cm pathlength IR gas cell, where the corresponding FT-IR spectra were acquired by accumulating 30 scans per spectrum with 2 cm(-1) nominal resolution. The method was applied to the determination of TMA in natural samples providing concentration values statistically comparables with those obtained by a head space gas chromatography (HS-GC) reference procedure. The sample throughput by FT-IR is increased by a factor of 6 as compared with HS-GC. PMID- 17723778 TI - Application of lead film electrode for simultaneous adsorptive stripping voltammetric determination of Ni(II) and Co(II) as their nioxime complexes. AB - An adsorptive stripping voltammetric (AdSV) procedure for simultaneous determination of Ni(II) and Co(II) in the presence of nioxime as a complexing agent at an in situ plated lead film electrode was described. The Co(II) signal was enhanced by exploitation of the catalytic process in the presence of nitrite. Ni(II) and Co(II) signals are better separated than in the case of bismuth film electrodes. Calibration graphs for an accumulation time of 120 s are linear from 1 x 10(-9) to 1 x 10(-7) mol L(-1) and from 1 x 10(-10) to 5 x 10(-9) mol L(-1) for Ni(II) and Co(II), respectively. The proposed procedure was applied for Ni(II) and Co(II) determination in water certified reference materials. PMID- 17723779 TI - Determination of tryptophan and histidine by adsorptive cathodic stripping voltammetry using H-point standard addition method. AB - A sequential method is proposed for the determination of tryptophane and histidine by adsorptive cathodic stripping voltammetry using standard addition and H-point standard addition method (HPSAM). The complexes of copper(II) with the amino acids were accumulated onto the surface of a hanging mercury drop electrode for 60s. Then the preconcentrated complexes were reduced by square wave voltammetry and the peak currents were measured. The effect of various parameters such as pH, concentration of copper, accumulation potential, accumulation time and scan rate on the sensitivity were studied by one-at-a time and artificial neural network. Under the optimized conditions, the peak currents at about +0.05 to -0.30 V is proportional to the concentration of tryptophan and histidine over the concentration ranges of 5-220 and 100-1200 nM, respectively. Optimization of the parameters by one-at-a time showed that at accumulation potential of 0.10 V (versus Ag/AgCl reference electrode) the peak current is proportional only to the concentration of tryptophan and histidine does not have any contribution to the current. The optimization results by artificial neural network showed that at accumulation potential of -0.06 V (versus Ag/AgCl) the peak current is proportional to the both concentrations of tryptophan and histidine. Therefore, the method of H-point standard addition has been used for resolving overlap voltamograms for determination of histidine in the present of tryptophane. The method was successfully applied to the determination of tryptophan and histidine in synthetic and real samples. PMID- 17723781 TI - Statistical design-principal component analysis optimization of a multiple response procedure using cloud point extraction and simultaneous determination of metals by ICP OES. AB - A procedure has been developed for the simultaneous determination of traces amounts of Cd, Cr, Cu, Mn, Ni and Pb from saline oil-refinery effluents and digested vegetable samples using inductively coupled plasma optical emission spectrometry (ICP OES). The procedure is based on cloud point extraction (CPE) of these metals as 2-(bromo-2-pyridylazo)-5-diethyl-amino-phenol (Br-PADAP) complexes into a micellar phase of octylphenoxypolyethoxyethanol (Triton X-114). Optimization of the procedure was performed by response surface methodology (RSM) using a Doehlert design. Principal components (PC) were used to simplify the multiple response analysis. A response surface for the first PC score is useful in determining the optimum conditions for the Cd, Cr, Cu, Mn and Pb determinations whereas the second PC is highly correlated with the Ni response. Improvement factors of 22, 36, 46, 25, 65 and 39, along with limits of detection (3sigma(B)) of 0.081, 0.79, 0.38, 0.83, 0.28 and 0.69 microg L(-1), and precision expressed as relative standard deviation (%R.S.D., n=8, 20.0 microg L(-1)) of 1.5, 2.2, 3.5, 2.6, 2.5 and 2.5 were achieved for Cd, Cr, Cu, Mn, Ni and Pb, respectively. The accuracy was evaluated by spike tests in oil-refinery effluent samples and analysis of a vegetable certified reference material (NIST 1571, orchard leaves). Results found were in agreement with certified values. PMID- 17723780 TI - Bismuth film electrode for anodic stripping voltammetric determination of tin. AB - The bismuth film electrode (BiFE), in combination with anodic stripping voltammetry, offers convenient measurement of low concentrations of tin. The procedure involves simultaneous in situ formation of the bismuth film electrode on a glassy carbon substrate electrode, together with electrochemical deposition of tin, in a non-deaerated model solution containing bismuth ions, catechol as complexing agent and the metal analyte, followed by an anodic stripping scan. The BiFE is characterized by an attractive electroanalytical performance, with two distinct voltammetric stripping signals corresponding to tin, accompanied with low background contributions. Several experimental parameters were optimized, such as concentration of bismuth ions and catechol, deposition potential, deposition time and pH of the model solution. In addition, a critical comparison is given with bare glassy carbon and mercury film electrodes, revealing the superior characteristics of BiFE for measurement of tin. BiFE exhibited highly linear behavior in the examined concentration range from 1 to 100 microg L(-1) of tin (R2=0.997), an LoD of 0.26 microg L(-1) tin, and good reproducibility with a calculated R.S.D. of 7.3% for 10 microg L(-1) tin (n=10). As an example, the practical applicability of BiFE was tested with the measurement of tin in a real sample of seawater. PMID- 17723782 TI - Validation and application of an analytical method for monomethylmercury quantification in aquatic plant tissues. AB - An analytical methodology for monomethylmercury (MMHg) determination in aquatic plant tissues with low detection limit (346 pg g(-1)) is proposed. It consists of acid digestion (HBr/CuSO4), cleanup step with a Na2S solution, pre-concentration procedure using a dithizone solution in toluene and quantification by GC-ECD. The performance of the methodology has been tested by determining the MMHg concentrations in the certified reference material Fucus Sea Plant Homogenate- IAEA-140/TM (CRM) and in leaves, stems and roots of the salt marsh plants Sarcocornia fruticosa and Halimione portulacoides. The results obtained for CRM were not statistically different (alpha=0.056) from the certified value and repeatability was lower than 2.5% for the plant samples analyzed. This coefficient of variation was similar to those obtained in the externally quality control using within-batch and between-batch (<1.4%). PMID- 17723783 TI - Preparation of novel ion exchange polyurethane foam and its application for separation and determination of palladium in environmental samples. AB - The new strong anion exchanger (PUFIX) from polyurethane foam was prepared by coupling of the primary amine of the foam matrix with ethyl iodide. PUFIX was characterized using different tools (IR spectra, elemental analysis, density and thermal analysis). The sorption properties of the new anion exchanger (PUFIX) and chromatographic behaviour for separation and determination of palladium(II) ions at low concentrations from aqueous iodide or thiocyanate media were investigated by a batch and dynamic processes. The maximum sorption of Pd(II) was in the pH range of 0.3-2. The kinetics of sorption of the Pd(II) by the PUFIX was found to be fast with average values of half-life of sorption (t(1/2)) of 3.32 min. The variation of the sorption of Pd(II) with temperature gives average values of DeltaH, DeltaS, DeltaG and DeltaE to be -38.3 kJ mol(-1), -100.7J K(-1) mol(-1), 8.3 and 11.8 kJ mol(-1), respectively. The sorption capacity of PUFIX was 1.69 mmol g(-1) for Pd(II), preconcentration factors of values approximately 250 and the recovery 99-100% were achieved (R.S.D. approximately 1.24%). The lower detection limit, 1.28 ng mL(-1) was evaluated using spectrophotometric method (R.S.D. approximately 2.46%). PMID- 17723784 TI - Phenols removal by immobilized tyrosinase reactor in on-line high performance liquid chromatography. AB - The development of an immobilized enzyme reactor (IMER) based on tyrosinase immobilized on aminopropyl-controlled pore glass (AP-CPG) for the removal of phenols from model aqueous solutions was reported. To elucidate the influence of the substrate nature, the apparent (V'max, K'm) and the inherent (Vmax, Km) Michaelis-Menten constants were determined by Lineweaver-Burk method and the external diffusional contributions on measured enzyme activities were removed by a graphical method. The dephenolization process was realized by recycling the phenol solutions through the bioreactor connected to a chitosan trap in order to remove the colored quinone-type products of the tyrosinase reactions. The results indicated that a complete removal of phenol derivatives in the range of 150-300 min, with the exception of 60% removal for phenol reached in 400 min, was obtained. The observed sequence: cresol > 4-methylcathecol > catechol > 4-Cl phenol phenol was in accordance to the V'max/K'm values. PMID- 17723787 TI - Management of distal humeral fractures in the elderly. AB - Although relatively uncommon, fractures of the distal humerus in the elderly patient population are significant injuries of which optimal management is a subject of debate in orthopaedic literature. The combination of complex anatomy, poor bone quality and extensive comminution often seen with these fractures makes successful treatment difficult. Currently, most surgeons support surgical fixation of distal humeral fractures with the belief that restoration of the patient's native elbow joint provides the best opportunity for a good functional outcome. Others have proposed the use of total elbow arthroplasty as a primary treatment method for geriatric distal humeral fractures based on the difficulties associated with ORIF and the relatively low demands of this patient population. To date, there have been no prospective randomised trials comparing these two treatment alternatives, and a comparison of available outcome data shows good functional outcome for both forms of fracture management. With the aging of the population and an associated increase in the incidence of distal humeral fractures, the debate over the optimal treatment regime will undoubtedly continue. PMID- 17723786 TI - The management of ankle fractures in the elderly. AB - In recent years, the incidence and severity of ankle fractures in the elderly population have increased. Although surgical fixation has gained wide acceptance for younger ankle fracture patients, controversy exists within the orthopaedic community with respect to the optimal way to manage these fractures in the geriatric patient population. Although some authors categorise ankle fractures in the elderly as fragility fractures associated with osteoporosis, it appears that risk factors such as increased weight, poly-pharmacy and propensity for falls play larger roles than poor bone quality. The presence of osteoporosis may increase the level of difficulty involved with the surgical management of these patients, leading some authors to alter their standard operative technique. Early studies cited high complication rates and poor outcome following operative intervention, however, more recent investigations have demonstrated successful functional outcomes following surgical management and appropriate postoperative rehabilitation. Based on the current evidence, the literature appears to support surgical fixation of displaced ankle fractures in the elderly patient population. PMID- 17723788 TI - Advances in the medical management of osteoporosis. AB - Osteoporosis is a skeletal disorder characterised by compromised bone strength predisposing to increased risk of fracture, which is rapidly reaching epidemic proportions as the population ages. Many patients presenting with a fracture caused by a fall from standing height or less are not on any kind of therapy and many patients who sustain these fragility fractures are not started on therapy by their orthopaedic surgeon. In 2004, the United States Surgeon General released a report on osteoporosis recommending that physicians adopt a pyramidal approach to therapy. The base of the pyramid includes calcium, vitamin D, physical therapy and fall prevention. The second level calls for management or elimination of secondary causes of osteoporosis. The third level consists of treatment with either anti-resorptive or anabolic medications. The orthopaedic surgeon is in an ideal position to diagnose fragility fractures and suggest treatment in the hope of preventing future fractures. Anti-resorptive and anabolic therapies currently available are discussed. PMID- 17723789 TI - Advances in the treatment of intracapsular hip fractures in the elderly. AB - A review of recent advances in the treatment of intracapsular hip fractures in the elderly patient is offered to provide some guidelines on choosing the appropriate treatment for a given patient. Alternatives discussed include open reduction and internal fixation versus arthroplasty; unipolar versus bipolar hemiarthroplasty versus total hip arthroplasty; cemented versus cementlless prostheses; and a surgical approach. These recommendations are based upon a review of the substantial literature on the subject and the author's own experience. It is recommended that patients more than 60-years-old with a femoral neck fracture be treated in the following manner: Patients with undisplaced, stable fractures perform an ORIF, patients with displaced fractures, replace the head of the femur, the use of a Moore or Thompson prostheses should be relegated to the medically infirm, minimally ambulatory patient, modular unipolar or bipolar (cemented stem) hemiarthroplasty has the most reliable and predictable outcome in most patients, an uncemented modular hemiarthroplasty should be considered in patients with significant cardiovascular risk factors, THA perhaps recommended for the "active elderly patient". The use of large heads and meticulous capsular repair techniques will reduce the early dislocation rate while still allowing excellent long-term functional outcomes. PMID- 17723790 TI - Locking plate technology and its role in osteoporotic fractures. AB - Osteoporosis is a public health issue that leads to increased morbidity and dependency in an increasing population. Fractures in osteoporotic bone have been a contraindication to internal fixation due to their past poor results. Various treatment methods and innovations have been attempted that have met with some success. This paper reviews one such innovation, locking-plate osteosynthesis, looking at its technology and success and its role in osteoporotic patients. As this is an evolving technology, surgeon's experience with these plates and screws are in advance of clinical studies and therefore the surgeons should proceed with caution when choosing locking plate technology in the treatment of osteoporotic fractures. PMID- 17723791 TI - Nonoperative management of osteoporotic vertebral compression fractures. AB - As the population ages, vertebral compression fractures are an increasing source of pain and dysfunction. The immobilisation that often occurs with fractures can lead to multiple medical complications and their management can be complex as care may require multiple treatment modalities. Each individual responds to pain differently and a treatment plan must be tailored to the individual's pain, functional limitations and goals. The likely first choice for managing stable osteoporotic vertebral compression fractures is conservative management. Treatment options usually involve a combination of medications, bracing and physical therapy. If radicular pain is a component of the pain syndrome, epidural steroid injections may be beneficial. In addition, some patients may benefit from vertebral augmentation. This paper reviews current recommendations for managing vertebral compression fractures. Treatment options including vertebral augmentation are reviewed, including indications and complications. PMID- 17723792 TI - The medical and economic impact of preoperative cardiac testing in elderly patients with hip fractures. AB - PURPOSE: To assess the medical and economic impact of preoperative cardiac testing (stress thallium imaging or echocardiography) on the treatment of elderly patients with hip fractures. MATERIALS AND METHODS: 235 consecutive patients over the age of 60 treated for a hip fracture (236 fractures) (OTA 31) at a single Level I trauma centre were identified from a prospective orthopaedic trauma database and studied as part of a retrospective cohort series. 35 (15%) had cardiac testing prior to treatment of their hip fracture. The indication for testing was a newly diagnosed cardiac abnormality in 16 of these cases and a prior history of cardiovascular disease without an acute cardiac problem in 19. RESULTS: Cardiac evaluation did not change the orthopaedic management in any case. No patient underwent cardiac surgery or coronary angioplasty as a result of the testing. In 48% of cases, cardiac testing did not lead to new medical treatment. In 52%, recommendations were only made for medical management of previously known cardiac disease. Patients who had cardiac testing had a significantly greater average delay to surgery (3.3 days) than those who did not (1.9 days), (P<.001). The cost of preoperative cardiac testing totalled more than $44,000 for the 35 patients. DISCUSSION AND CONCLUSION: Preoperative cardiac testing did not lead to changes in perioperative orthopaedic or medical management of elderly patients with hip fractures. Patients undergoing testing had a significant delay to surgery. Extrapolated to the population of elderly hip fracture patients in the United States (250,000 annually), preoperative cardiac testing (performed in 15% of cases) would cost nearly $47,000,000 annually. Preoperative cardiac testing may add profoundly to the healthcare costs associated with treating this population of patients without influencing orthopaedic or medical management. PMID- 17723793 TI - Operative management of periprosthetic femur fractures in the elderly using biological fracture reduction and fixation techniques. AB - Treatment of periprosthetic femur fractures often requires deviation from standard fixation techniques due to the presence of associated arthroplasty components, however, the use of adjuvant bone grafts and bone graft substitutes remain controversial. 59 patients (average age, 74 years) with either a periprosthetic femoral shaft about an arthroplasty stem (n=29) or supracondylar fracture above a total knee arthroplasty (n=30) were treated with biological open reduction internal-fixation techniques without the use of bone grafts or bone graft substitutes. All except one patient healed after the index procedure. Three patients had progressive malalignment associated with failed screw fixation but all healed without further surgical intervention. 49 out of the 59 patients returned to their baseline level of function. These results indicate that use of adjuvant bone graft materials may not be routinely necessary when treating periprosthetic femur fractures using lateral plates and biological reduction and fixation techniques. PMID- 17723794 TI - Current concepts in plate and screw fixation of osteoporotic proximal humerus fractures. AB - Most surgeons feel that angular stable implants have improve the ability to obtain reliable fixation of an osteoporotic fracture of the proximal humerus fracture, but complications such as varus fracture collapse and screw penetration of the articular surface remain problematic. The use of limited drilling, blunt tipped locking bolts and routine incorporation of the rotator cuff into the internal fixation construct may help limit these complications. It may be of benefit to replace the concept of standard screw fixation of the osteoporotic proximal humerus with a concept of an angular stable scaffold support of the subchondral bone combined with fixation that does not rely on bone quality and utilizes the more predictable fixation of sutures through the rotator cuff attachments. PMID- 17723795 TI - Biomechanics of osteoporotic fractures. AB - The objective of this review article is to present biomechanics concepts and data relevant to osteoporotic fractures. Fractures are mechanical events that occur when the applied load exceeds the fracture load (bone strength); both loading and strength must be considered to understand fracture risk. Hip fractures are almost always due to a fall, but only 5% of falls result in fracture. Hip fracture risk is greatest for a sideways fall that impacts on the greater trochanter. The loading events that cause vertebral fractures are poorly understood but include falls and heavy lifting. Activities that involve forward flexion and lifting generate the largest forces on the spine. Factors that affect bone strength include bone size (geometry) and bone density (vBMD). Men have larger bones at all ages compared to women and this is the main factor in the gender difference in whole-bone strength. Both men and women lose trabecular bone density and thus bone strength with aging, which is the main reason for the age-related loss of bone strength at the hip and spine, although dramatic decreases in the toughness of cortical bone may also contribute to osteoporotic fragility. The factor of risk (applied force/fracture force) is a useful concept for considering both the injury and the disease component of osteoporotic fractures. Within this article, I will review data on age-related changes in factors that affect fracture risk. Advanced engineering concepts will not be presented, but a familiarity with basic mechanical principles is assumed. PMID- 17723796 TI - Are there advances in the treatment of extracapsular hip fractures in the elderly? AB - While the rate of failure following hip fracture surgery for extracapsular hip fractures in the elderly is low, an incidence of implant cutout from the femoral head remains regardless of whether fixation is by sliding hip screw or intramedullary nail. In general, a well-executed osteosynthesis is the best assurance of a good outcome with few complications, and typically a less than ideal placement of the implant in the femoral head is the reason for cut-out and failure of the operation. It is clear that there is no difference in the incidence of complications or functional outcome between a sliding hip screw and an intramedullary nail for pertrochanteric fractures (AO/OTA 31-A1 and A2), while the implant of choice in the elderly for the true intertrochanteric fracture (AO/OTA 31-A3; reverse intertrochanteric) is a nail. However, what is less clear is whether there are newer ideas and/or implant designs that represent true advances in the treatment of extracapsular fractures in the elderly. The following review focuses on just this issue. PMID- 17723797 TI - Vertebral augmentation in osteoporotic fractures. AB - Osteoporotic vertebral compression fractures result in an enormous medical, social and economic burden to society. Here, we review osteoporotic vertebral compression fractures, focusing on both their diagnosis and the treatment options, particularly vertebral augmentation. PMID- 17723798 TI - Robotics in cardiac surgery: the Emperor's new clothes. PMID- 17723799 TI - The seven stages of an idea. PMID- 17723800 TI - Bone marrow-derived mononuclear cell transplantation improves myocardial recovery by enhancing cellular recruitment and differentiation at the infarction site. AB - OBJECTIVE: Stem cell therapy in myocardial infarction is under intensive investigation; however, the mechanisms of recovery and the optimal transplantation technique remain controversial. The goal of this controlled and randomized study was to test the hypothesis that locally injected bone marrow derived mononuclear cells can focus in on the damaged myocardium and improve cardiac function by means of active participation in remodeling. METHODS: Myocardial infarction was introduced through occlusion of the circumflex coronary artery for 90 minutes in 14 piglets (24.0 +/- 4.9 kg) that were randomized to a cell-therapy group (n = 7) and a control group (n = 7). At reperfusion, autologous purified prelabeled or unlabeled cells (10(8) cells/2 mL) or saline were injected into the myocardium. Cardiac function was measured by using echocardiography preoperatively and postoperatively and at 3 weeks, when hearts were collected for histopathologic examination. RESULTS: The ejection fraction recovered in the cell-therapy group (P = .02) but failed to recover in the control group, and at 3 weeks, it remained at the lower level compared with that in the cell-therapy group (P = .067). The number of living cells in the necrotic area was significantly greater in the cell-therapy group (P < .001). Labeled cells were detected in the infarcted area, and they showed signs of myocyte differentiation. Furthermore, the proportional area of muscle actin-positive cells at the granulation area was higher in the cell-therapy group (P = .035). CONCLUSIONS: Autologous bone marrow-derived mononuclear cells at the infarcted area localize in the myocardium. The exact mechanism of recovery remains to be determined, but our findings may give new information concerning the cellular events that occur during cell therapy-enhanced recovery. PMID- 17723801 TI - Left ventricular pacing site and timing optimization during biventricular pacing using a multielectrode patch in pigs. AB - OBJECTIVES: Biventricular pacing is important therapy for congestive heart failure, reversing left ventricular dysfunction in dilated cardiomyopathy. Although left ventricular lead location and right ventricular-left ventricular delay are believed to be critical in biventricular pacing, there is no established technique for optimizing pacing site and timing. METHODS: After median sternotomy in 8 anesthetized pigs, an ultrasonic flow probe was placed on the ascending aorta to measure cardiac output, and pressure catheters were inserted into both ventricles. Temporary bipolar epicardial pacing leads were attached to the right atrium and anterior right ventricle. A patch with 5 bipolar electrodes was placed behind the left ventricle. A temporary bipolar lead was also placed on the left ventricular apex. Complete heart block was established by ethanol ablation. Right ventricular pressure overload was induced by snaring the pulmonary artery until right ventricular systolic pressure doubled. Dual-chamber mode biventricular pacing was instituted at 9 right ventricular-left ventricular delays, +80 ms to -80 ms in 20 ms increments, and 6 left ventricular sites. Data from the 54 combinations of these variables were acquired in a randomized fashion. Mixed model technology was used for statistical analysis. RESULTS: Qualitatively, two unique site/timing pairs were optimal. Statistically, pacing the obtuse margin at a right ventricular-left ventricular delay of +60 ms (mean cardiac output = 1.80 L/min) and the inferolateral wall at a right ventricular left ventricular delay of -20 ms (mean cardiac output = 1.79 L/min) was superior to all other site/timing combinations (mean cardiac output = 1.71 L/min; P = .006). CONCLUSIONS: Left ventricular pacing site and right ventricular-left ventricular delay can be optimized with a multielectrode patch and randomized data collection. This technique can be used further in clinical studies. PMID- 17723802 TI - Time-dependent response of both ventricles after septal ablation: implications for biventricular support after left ventricular assist device placement. AB - OBJECTIVES: An ovine model of septal ablation was studied to elucidate the mechanisms involved in right ventricular failure when commencing left ventricular mechanical assistance. The disruption of ventricular interdependence after acute and chronic septal injury was examined. METHODS: Twelve sheep underwent percutaneous transluminal septal myocardial ablation using 0.6 mL ethanol. Twelve other sheep underwent a sham procedure. Left ventricular and right ventricular pressure and volume (conductance) response 15 minutes and 4 weeks postinjury were measured. Ultrasonic crystals measured chamber dimensions and wall movement. Areas at risk and infarct zones were quantified. RESULTS: Compared with sham, ablation chronically reduced systolic interventricular septal thickening (18.4% +/- 5.8% vs 7.3% +/- 3.1%; P < .001) and acutely increased right ventricular ejection fraction (37.6% +/- 8.5% vs 69.9% +/- 7.2%; P < .001), preload recruitable stroke work (42.0 +/- 4.4 erg x 10(3) vs 48.7 +/- 2.0 erg x 10(3), P < .001), end-systolic elastance (1.03 +/- 0.19 mm Hg mL(-1) vs 1.31 +/- 0.18 mm Hg mL(-1); P < .001), and Tau (24.9 +/- 3.8 ms vs 29.6 +/- 8.2 ms; P < .001). In contrast, for left ventricular ejection fraction (55.5% +/- 5.9% vs 38.9% +/- 7.7%; P < .001), preload recruitable stroke work (85.9 +/- 10.6 mm Hg vs 66.5 +/- 9.6 mm Hg; P < .001) and elastance (2.13 +/- 0.51 mm Hg mL(-1) vs 1.81 +/- 0.44 mm Hg mL(-1); P < .001) were reduced, but Tau increased (22.0 +/- 3.5 ms vs 28.9 +/- 5.8 ms; P < .001) and remained elevated at 4 weeks compared with sham. The area at risk was the same between groups, and injury was limited to the septum (17.2% +/- 2.7% vs 2.9% +/- 5.8%; P < .001). CONCLUSIONS: Acute and chronic hemodynamic responses are distinctly different after septal injury; the acute response demonstrates a paradoxical motion. Resolution of this motion at 4 weeks is suggestive of reduced septal compliance and buttressing. Ventricular interactions after placement of a left ventricular assist device will vary depending on the injury duration. PMID- 17723803 TI - Elevated flow rate during cardiopulmonary bypass is associated with fluid accumulation. AB - OBJECTIVE: High flow rates during cardiopulmonary bypass are assumed to increase fluid accumulation. This study aimed to determine whether two different flow rates during cardiopulmonary bypass alter the intraoperative fluid balance and extravasation rate. METHODS: Sixteen pigs underwent 60 minutes of normothermic bypass, followed by 90 minutes of hypothermic bypass. A high-flow group (HF group, n = 8) had a cardiopulmonary bypass flow rate of 110 mL x kg(-1) x min(-1) and a low-flow group (LF group, n = 8) had a rate of 80 mL x kg(-1) x min(-1). Blood chemistry, hemodynamic parameters, plasma and interstitial colloid osmotic pressure, net fluid balance, plasma volume, fluid extravasation rate, and total tissue water content were measured or calculated. Results are presented as mean (standard deviation). RESULTS: The average net fluid balance during cardiopulmonary bypass was 1.02 (0.25) and 0.73 (0.23) mL x kg(-1) x min(-1) in the HF group and LF group, respectively (P < .05). The average fluid extravasation rate was 0.98 (0.22) and 0.77 (0.22) mL x kg(-1) x min(-1) in the HF group and the LF group (P = .07). Total water content was higher in the kidneys (P < .05) and tended to be higher in the lungs (P = .05), liver (P = .07), and brain (P = .07) of the HF group than in those of the LF group. The between-group differences in net fluid balance and fluid extravasation rate were present during the first 30 minutes of normothermic cardiopulmonary bypass. Thereafter, the values stabilized and remained similar in the two groups. Plasma volume and systemic vascular resistance differed between the groups. CONCLUSION: Cardiopulmonary bypass flow rate of 110 mL x kg(-1) x min(-1) was associated with higher positive net fluid balance and fluid extravasation rate than 80 mL x kg( 1) x min(-1). The effect was mainly observed in the initial phase of cardiopulmonary bypass. PMID- 17723804 TI - Prolonged extracorporeal membrane oxygenation-assisted support provides improved survival in hypothermic patients with cardiocirculatory arrest. AB - OBJECTIVE: Extracorporeal circulation is considered the gold standard in the treatment of hypothermic cardiocirculatory arrest; however, few centers use extracorporeal membrane oxygenation instead of standard extracorporeal circulation for this indication. The aim of this study was to evaluate whether extracorporeal membrane oxygenation-assisted resuscitation improves survival in patients with hypothermic cardiac arrest. METHODS: A consecutive series of 59 patients with accidental hypothermia in cardiocirculatory arrest between 1987 and 2006 were included. Thirty-four patients (57.6%) were resuscitated by standard extracorporeal circulation, and 25 patients (42.4%) were resuscitated by extracorporeal membrane oxygenation. Accidental hypothermia was caused by avalanche in 22 patients (37.3%), drowning in 22 patients (37.3%), exposure to cold in 8 patients (13.5%), and falling into a crevasse in 7 patients (11.9%). Multivariate logistic regression analysis was used to compare extracorporeal membrane oxygenation with extracorporeal circulation resuscitation, with adjustment for relevant parameters. RESULTS: Restoration of spontaneous circulation was achieved in 32 patients (54.2%). A total of 12 patients (20.3%) survived hypothermia. In the extracorporeal circulation group, 64% of the nonsurviving patients who underwent restoration of spontaneous circulation died of severe pulmonary edema, but none died in the extracorporeal membrane oxygenation group. In multivariate analysis, extracorporeal membrane oxygenation assisted resuscitation showed a 6.6-fold higher chance for survival (relative risk: 6.6, 95% confidence interval: 1.2-49.3, P = .042). Asphyxia-related hypothermia (avalanche or drowning) was the most predictive adverse factor for survival (relative risk: 0.09, 95% confidence interval: 0.01-0.60, P = .013). Potassium and pH failed to show statistical significance in the multivariate analysis. CONCLUSIONS: Extracorporeal rewarming with an extracorporeal membrane oxygenation system allows prolonged cardiorespiratory support after initial resuscitation. Our data indicate that prolonged extracorporeal membrane oxygenation support reduces the risk of intractable cardiorespiratory failure commonly observed after rewarming. PMID- 17723805 TI - Neurologic outcomes of thymectomy in myasthenia gravis: comparative analysis of the effect of thymoma. AB - OBJECTIVES: The objectives of this study were to compare the clinical features and the outcomes after thymectomy between patients with and without thymoma and to evaluate the influence of thymectomy on the subsequent clinical course of myasthenia gravis. METHODS: Between 1995 and 2003, 64 consecutive patients underwent thymectomy, and of these, 60 patients were followed up for at least 12 months postoperatively. The study population was divided into 2 groups based on the presence of thymoma. We performed a retrospective analysis to compare the neurologic outcomes of thymectomy between patients with thymomatous myasthenia gravis and those with nonthymomatous myasthenia gravis. RESULTS: Twenty-four patients had a thymoma. No significant differences were observed between the 2 groups regarding the preoperative severity of myasthenia gravis. There was no significant difference in the follow-up duration between the 2 groups. There was no significant difference in the overall remission rate between the 2 groups (P = .064). The mean time required to reach a remission was 10.6 months and 23.5 months in the thymoma and nonthymoma groups, respectively. The mean duration of remission was 43.1 months and 30.8 months in the thymoma and nonthymoma groups, respectively. In the early phase of follow-up, more patients reached remission in the thymoma group than those in the nonthymoma group (P = .040). CONCLUSIONS: Neurologic outcomes of the thymoma group were no worse than those of the nonthymoma group. It is expected that earlier thymectomy is likely to result in a better prognosis by shortening the disease period, even for patients with nonthymomatous myasthenia gravis. PMID- 17723806 TI - Use of tissue expanders in adult postpneumonectomy syndrome. AB - OBJECTIVE: Mediastinal shift and rotation after pneumonectomy can lead to severe symptomatic airway compression. Historically, a variety of treatments, such as muscle-flap transposition, pericardial fixation, and plombage, have been used. In this study we retrospectively evaluated the effectiveness of intrathoracic tissue expansion in postpneumonectomy syndrome. METHODS: Since 1990, our center has used tissue expanders as plombage in patients with postpneumonectomy syndrome. Between 1990 and 2005, a total of 20 patients were treated. The outcome was evaluated by using preoperative, perioperative, and postoperative bronchoscopy and imaging studies. Patient satisfaction was determined with a validated questionnaire. RESULTS: In 19 of the 20 patients, up to 3 tissue expanders were placed and filled within the pleural cavity. Access to the pleural cavity could not be obtained in 1 patient because of adhesions. Perioperative and postoperative bronchoscopic scans demonstrated decompression of the left main bronchus in 16 (84%) of 19 patients. On discharge, all patients reported improvement of their respiratory symptoms. Six (32%) patients required reoperation because of herniation (n = 2), luxation (n = 1), inadequate positioning (n = 2), and leakage of the tissue expander (n = 4). In 4 patients additional filling was performed in the outpatient clinic, with immediate improvement of respiratory distress. CONCLUSION: Use of tissue expanders in adults with postpneumonectomy syndrome is an effective means of decompressing the remaining bronchus, thereby leading to a significant improvement in respiratory symptoms. Although 32% of patients required reoperation for complications, each complication was readily correctable. PMID- 17723807 TI - Effects of head-down tilt on intrapulmonary shunt fraction and oxygenation during one-lung ventilation in the lateral decubitus position. AB - OBJECTIVE: During one-lung ventilation, surgical positions significantly affect deterioration of oxygenation, and the lateral decubitus position is superior in preventing dangerous hypoxemia compared with the supine position. However, additional head-down tilt causes more compression of the dependent ventilated lung by the abdominal contents and may result in dangerous hypoxemia, as occurs in the supine position. Therefore, we evaluated the effect of head-down tilt on intrapulmonary shunt and oxygenation during one-lung ventilation in the lateral decubitus position. METHODS: Thirty-four patients requiring one-lung ventilation were randomly allocated to the control group (n = 17) or the head-down tilt group (n = 17). Hemodynamic and respiratory variables were measured 15 minutes after one-lung ventilation in the lateral decubitus position (baseline), 5 and 10 minutes after a 10-degree head-down tilt (T5 and T10, respectively), and 10 minutes after the patient was returned to a horizontal position (T20) in the head down tilt group. Measurements were done at the same time points in the control group without head-down tilting. RESULTS: In the head-down tilt group, cardiac filling pressures were increased after head-down tilt without any changes in cardiac index. Percent change of shunt to baseline value was significantly increased at T10 and T20 in the head-down tilt group. Percent change of arterial oxygen tension to baseline value was significantly decreased at T5, T10, and T20 in the head-down tilt group, whereas it was decreased only at T20 in the control group. CONCLUSION: Head-down tilt during one-lung ventilation in the lateral decubitus position caused a significant increase in shunt and a decrease in percent change of arterial oxygen tension, without causing dangerous hypoxemia. PMID- 17723808 TI - Sarcomatoid lung cancer (spindle/giant cells): an aggressive disease? AB - OBJECTIVE: We investigated the clinical, surgical, and pathologic features of sarcomatoid lung carcinomas with spindle/giant cells, giving special attention to the prognostic behavior of these rare tumors. METHODS: Surgical specimens from 39 patients (29 men and 10 women; mean age, 61 years) were examined by means of light microscopy. Preoperative and postoperative data were collected, and survival was calculated by using the Kaplan-Meier method. RESULTS: Nineteen patients were diagnosed with cancer preoperatively. Only one sarcomatoid tumor had been diagnosed. Presenting symptoms were noted in 85% of patients, and complete resection was achieved in 37 tumors. Postoperative pTNM staging: T2/T3/T4, 22/15/2; N0/N1/N2, 28/8/3; 15 stage IB, 14 stage IIB, 7 stage IIIA, 2 stage IIIB, and 1 stage IV. Histopathologic analysis revealed necrosis in 90% of the tumors (34 pleomorphic, 3 spindle cell, and 2 giant cell carcinomas). During follow-up (median, 24 months), 21 patients died of disease recurrence, and 3 died of postoperative complications. The 5-year survival rate (33%; median, 11 months) was negatively influenced by large tumors (7.5% survival for > or =7 cm vs 56% for <7 cm, P = .0026). The disease-free interval was significant for patients who relapsed (0% for disease-free interval <6 months vs 33% for disease-free interval > or =6 months, P = .0019). CONCLUSIONS: A highly heterogeneous group, spindle/giant cell lung carcinomas tend to be symptomatic, peripheral, and necrotic. Preoperative diagnosis is difficult. Most patients in our study relapsed and died the first year after surgical intervention. Surgical intervention can permit long-term survival, but adjuvant therapy warrants consideration because of the aggressive nature of these tumors. PMID- 17723809 TI - Risk-adjusted econometric model to estimate postoperative costs: an additional instrument for monitoring performance after major lung resection. AB - OBJECTIVES: The objectives of this study were to develop a risk-adjusted model to estimate individual postoperative costs after major lung resection and to use it for internal economic audit. METHODS: Variable and fixed hospital costs were collected for 679 consecutive patients who underwent major lung resection from January 2000 through October 2006 at our unit. Several preoperative variables were used to develop a risk-adjusted econometric model from all patients operated on during the period 2000 through 2003 by a stepwise multiple regression analysis (validated by bootstrap). The model was then used to estimate the postoperative costs in the patients operated on during the 3 subsequent periods (years 2004, 2005, and 2006). Observed and predicted costs were then compared within each period by the Wilcoxon signed rank test. RESULTS: Multiple regression and bootstrap analysis yielded the following model predicting postoperative cost: 11,078 + 1340.3X (age > 70 years) + 1927.8X cardiac comorbidity - 95X ppoFEV1%. No differences between predicted and observed costs were noted in the first 2 periods analyzed (year 2004, $6188.40 vs $6241.40, P = .3; year 2005, $6308.60 vs $6483.60, P = .4), whereas in the most recent period (2006) observed costs were significantly lower than the predicted ones ($3457.30 vs $6162.70, P < .0001). CONCLUSIONS: Greater precision in predicting outcome and costs after therapy may assist clinicians in the optimization of clinical pathways and allocation of resources. Our economic model may be used as a methodologic template for economic audit in our specialty and complement more traditional outcome measures in the assessment of performance. PMID- 17723810 TI - Surgical treatment of synchronous multiple primary lung cancers: experience of 92 patients. AB - OBJECTIVES: According to our previous study, the concurrent detection of p53 and epidermal growth factor receptor mutations significantly improves the clonality assessment and impact management of patients with multiple primary lung cancer. Nevertheless, the treatment, outcome, and safety of patients with this complex disease remain controversial. This series of cases detail our experiences with surgical resections in 92 patients during the past 16 years. METHODS: A database of 1651 patients was evaluated for unilateral and bilateral synchronous multiple primary lung cancers. The relationships among the location of tumors, number of tumors, tumor size, tumor histology, vascular invasion, regional lymph node metastasis, extranodal extension, type of surgery, mortality, and survival were analyzed. RESULTS: The 5-year survival for all synchronous multiple primary lung cancers was 35.3%. The overall surgical mortality was 1.1%. Notably, lymph node metastasis, extranodal extension, vascular invasion, tumors with adenosquamous carcinoma or different histology, and poor survival were observed. Multivariate analysis showed that only the occurrence of lymph node metastasis remained a statistically significant prognostic factor. The 5-year survivals were 15.5% [corrected] and 52.5% [corrected] for patients with and without lymph node metastasis, respectively (P < .001). CONCLUSION: An aggressive surgical approach is safe and justified in patients with synchronous multiple primary lung cancers and node-negative diseases. The status of this particular form of non-small cell lung cancers might be considered in the conventional TNM staging system for more accurate prediction of patient prognosis. PMID- 17723811 TI - Prognostic factors in resected stage I non-small cell lung cancer with a diameter of 3 cm or less: visceral pleural invasion did not influence overall and disease free survival. AB - OBJECTIVE: Resection is the treatment of choice for patients with stage I non small cell lung cancer. Stage I non-small cell lung cancer has been further subdivided into IA (T1N0M0, tumor size < or = 3 cm without visceral pleural invasion) and IB (T2N0M0, tumor size > 3 cm or any size with visceral pleural invasion). The aim of this study was to evaluate the prognostic factors in patients with resected stage I non-small cell lung cancer with a diameter of 3 cm or less. METHODS: We retrospectively reviewed the clinicopathologic characteristics of 445 patients with resected stage I non-small cell lung cancer with a diameter of 3 cm or less who were treated at Taipei Veterans General Hospital between 1980 and 2000. Disease-free survival, overall survival, and their predictors were analyzed. RESULTS: The 5- and 10-year overall survivals were 61.4% and 40.0%, respectively. The 5- and 10-year disease-free survivals were 74.5% and 73.4%, respectively. Tumor size, smoking index, and number of mediastinal lymph nodes dissected were significant predictors for both disease free survival (P = .009, P = .002, and P = .006, respectively) and overall survival (P = .004, P < .001, and P = .001, respectively) in multivariate analyses. Visceral pleural invasion did not influence overall survival or disease free survival. CONCLUSIONS: Tumor size, smoking index, and number of mediastinal lymph nodes dissected were prognostic factors for both overall survival and disease-free survival in resected stage I non-small cell lung cancer with a diameter of 3 cm or less. Small tumors (<3 cm) of stage IB (T2N0M0) non-small cell lung cancer with visceral pleural invasion should be treated as T1 disease and not T2 disease. PMID- 17723812 TI - Description of regional mitral annular nonplanarity in healthy human subjects: a novel methodology. AB - OBJECTIVE: Finite-element analysis demonstrates that the nonplanar shape of the mitral annulus diminishes mitral leaflet stress. It has therefore been postulated that repair with annuloplasty rings that maintain the nonplanar shape of the annulus could increase repair durability. Although the global nonplanarity of the mitral annulus has been adequately characterized, design of such a ring requires a quantitative description of regional annular geometry. By using real-time 3 dimensional echocardiography in conjunction with available image processing software, we developed a methodology for describing regional annular geometry and applied it to the characterization of the normal human mitral annulus. METHODS: Five healthy volunteers underwent mitral valve imaging with real-time 3 dimensional echocardiography. Regional annular height was calculated at 36 evenly spaced intervals. RESULTS: Maximal annular height/commissural width ratio was found to occur at the midpoint of the anterior annulus in all cases. These values averaged 26% +/- 3.1%, whereas those for the midposterior annulus averaged 18% +/ 3.0%. The average commissural width was 35.2 +/- 6.0 mm. Although substantial spatial heterogeneity was observed, regional annular height at a given rotational position was highly conserved among subjects when normalized to commissural width. CONCLUSIONS: These quantitative imaging and analytic techniques demonstrate that the normal human mitral annulus is regionally heterogeneous in its nonplanarity, and they establish a means of describing annular geometry at a regional level. With wider application, these techniques may be used both to characterize pathologic annular geometry and to optimize the design of mitral valve annuloplasty devices. PMID- 17723813 TI - Patency rates of endoscopically harvested radial arteries one year after coronary artery bypass grafting. AB - OBJECTIVES: To improve patients' acceptance of the radial artery as a graft for coronary revascularization, we introduced an endoscopic harvesting technique. The aim of this study was to assess graft quality 1 year after the operation. METHODS: In 50 patients who underwent endoscopic radial artery harvesting for coronary artery bypass grafting, 64-slice computed tomography, electrocardiography, and echocardiography were utilized to assess graft patency and left ventricle function at a 1-year follow-up. In addition, the influencing factors of radial artery graft patency were evaluated. Radial artery patency was compared with a control group from our database. RESULTS: Any patency of endoscopically harvested radial artery grafts was 78% (39/50) and perfect patency was 72% (36/50) 1 year after coronary revascularization. The implanting surgeon and graft harvester, patient factors, graft properties, medication, and target territory did not influence the patency rates of the radial artery graft. The only significant and strong parameter to predict perfect graft patency was the severity of the target vessel stenosis (P < .001). In patients with a target vessel stenosis of 90% or greater, radial artery graft patency was 90.3% (28/31). Patency rates of endoscopically (72%) and conventionally (74%) harvested radial arteries were not different (P = .822). CONCLUSIONS: Patency rates 1 year after endoscopic radial artery harvesting are comparable to the open technique. On the basis of our results, we attempt to use the radial artery as a bypass graft only for target coronary arteries with 90% or greater stenosis. We recommend endoscopic harvesting as the technique of choice to harvest the radial artery. PMID- 17723814 TI - Opening and closing kinematics of fresh and calcified aortic valve prostheses: an in vitro study. AB - OBJECTIVES: In vitro testing of biologic valves has been performed using only fresh but treated valves suitable for patient implantation. The present study investigates changes in hemodynamic performance and leaflet kinematics in progressively calcified porcine and pericardial aortic valve prostheses. METHODS: Edwards Perimount Magna (Edwards Lifesciences, Irvine, Calif) (n = 5) and Medtronic Mosaic Ultra (Medtronic Inc, Minneapolis, Minn) (n = 5) heart valves (23 mm) were investigated in an artificial circulation system (70 beats/min, cardiac output 5 L/min). Leaflet kinematics were visualized with a high-speed camera (3000 frames/sec). Valves were then exposed to a calcium-phosphate solution at a constant pulse rate of 300 beats/min for a total of 6 weeks. Repeated testing was performed after 1, 2, 3, 4, and 6 weeks of calcification. The calcification process might not be similar to in vivo performance. RESULTS: Initially, the Perimount Magna valves demonstrated lower pressure gradients compared with the Mosaic Ultra valves (9.7 +/- 0.36 mm Hg vs 14.0 +/- 1.16 mm Hg), but they showed higher closing volume and leakage flow. Total energy loss was equivalent after 1 week of calcification. Perimount Magna valves calcified significantly faster and more severely, leading to an increase in gradients and closure volume. Leaflet kinematics showed progressively longer opening and closing times for the pericardial valves (closing time Perimount Magna 135 +/- 11 msec vs Mosaic Ultra 85 +/- 9 msec after 6 weeks). CONCLUSIONS: On the basis of visual inspection, despite the new ThermaFix (Edwards Lifesciences) tissue treatment, the Perimount Magna pericardial valves calcified in vitro faster and more severely than did the Mosaic Ultra porcine valves, which demonstrated a more constant performance throughout the calcification process. Leaflet kinematics showed a progressive prolongation of opening and closing times for pericardial valves, leading to higher closing volume. PMID- 17723815 TI - Cumulative sum failure analysis for eight surgeons performing minimally invasive direct coronary artery bypass. AB - OBJECTIVE: Analysis of average and individual surgical performance for minimally invasive direct coronary artery bypass was used to enhance quality control for that operation. METHODS: A total of 1441 standard minimally invasive direct coronary artery bypass procedures performed from August 1996 to January 2006 were analyzed for mortality and 10 other major perioperative complications. Learning curves and assessment of perioperative outcome were calculated using descriptive statistics and cumulative sum observed minus expected failure analysis for 8 involved surgeons with a personal experience ranging from 27 to 443 procedures. RESULTS: The incidence of in-hospital mortality was 0.9% and compared favorably with the predicted mortality calculated by the logistic EuroSCORE (3.6%, P < .01). Cumulative sum analysis revealed that 2 surgeons crossed the 95% reassurance boundary after 50 operations and that 2 surgeons crossed the 95% reassurance boundary after 100 operations. There were significant differences between surgeons with regard to the learning curves and perioperative complications (3.6%-29.6%, P < .01). Two surgeons crossed the 95% alarm-line indicating unacceptably high failure rates. CONCLUSIONS: Minimally invasive direct coronary artery bypass has become a procedure with low mortality and low complication rates, but results are case-load and surgeon dependent. Cumulative sum analysis is a valuable method allowing for a breakdown of complication rates over time displaying individual surgeons' strengths. PMID- 17723816 TI - Staphylococcus aureus poststernotomy mediastinitis: description of two distinct acquisition pathways with different potential preventive approaches. AB - OBJECTIVE: Determining the acquisition routes of infection is crucial to designing specific preventive approaches against Staphylococcus aureus poststernotomy mediastinitis. METHODS: From 2002 to 2004, a nasal sample was obtained from patients before cardiac surgery. We collected clinical and microbiologic data of all episodes of S aureus poststernotomy mediastinitis. A case-control study (3:1) was performed to confirm the role of previous preoperative nasal colonization by S aureus as a risk factor for S aureus poststernotomy mediastinitis. Pulsed field gel electrophoresis molecular analysis of nasal and surgical site S aureus isolates was performed to analyze their relatedness in each patient with poststernotomy mediastinitis and with other patients of the study cohort. RESULTS: S aureus nasal cultures were positive in 228 (15.9%) of 1432 patients: methicillin-susceptible S aureus in 222 (15.5%) and meticillin-resistant S aureus in 6 (0.4%). S aureus poststernotomy mediastinitis was diagnosed in 17 (1.2%) of 1432 patients: 9 (3.95%) of 228 in colonized patients versus 8 (0.66%) of 1204 in noncolonized patients (P < .0001). Seven of 9 patients (1.2%) with methicillin-susceptible S aureus had an identical isolate by pulsed field gel electrophoresis in preoperative nasal and surgical-site cultures, but no clonal relatedness was shown among the isolates from these 9 patients. None of the 8 patients with methicillin-resistant S aureus poststernotomy mediastinitis had an identical isolate by pulsed field gel electrophoresis in preoperative nasal and surgical-site cultures, and the same clone of methicillin-resistant S aureus was responsible for all these cases. CONCLUSIONS: Endogenous [corrected] nasal colonization often precedes methicillin resistant S aureus poststernotomy mediastinitis, which suggests that preoperative [corrected] decontamination is adequate for preventing methicillin-susceptible [corrected] S aureus poststernotomy mediastinitis, whereas hospital infection control measures seem to be the major factor for preventing methicillin-resistant S aureus poststernotomy mediastinitis. PMID- 17723817 TI - Does right thoracotomy increase the risk of mitral valve reoperation? AB - OBJECTIVE: The study objective was to determine whether a right thoracotomy approach increases the risk of mitral valve reoperation. METHODS: Between January of 1993 and January of 2004, 2469 patients with mitral valve disease underwent 2570 reoperations (1508 replacements, 1062 repairs). The approach was median sternotomy in 2444 patients, right thoracotomy in 80 patients, and other in 46 patients. Multivariable logistic regression was used to identify factors associated with median sternotomy versus right thoracotomy, mitral valve repair versus replacement, hospital death, and stroke. Factors favoring median sternotomy (P < .03) included coronary artery bypass grafting (30% vs 2%), aortic valve replacement (39% vs 2%), tricuspid valve repair (27% vs 13%), fewer previous cardiac operations, more recent reoperation, and no prior left internal thoracic artery graft. These factors were used to construct a propensity score for risk-adjusting outcomes. RESULTS: Hospital mortality was 6.7% (163/2444) for the median sternotomy approach and 6.3% (5/80) for the thoracotomy approach (P = .9). Risk factors (P < .04) included earlier surgery date, higher New York Heart Association class, emergency operation, multiple reoperations, and mitral valve replacement. Stroke occurred in 66 patients (2.7%) who underwent a median sternotomy and in 6 patients (7.5%) who underwent a thoracotomy (P = .006). Mitral valve replacement (vs repair) was more common in those receiving a thoracotomy (P < .04). CONCLUSIONS: Compared with median sternotomy, right thoracotomy is associated with a higher occurrence of stroke and less frequent mitral valve repair. Specific strategies for conducting the operation should be used to reduce the risk of stroke when right thoracotomy is used for mitral valve reoperation. In most instances, repeat median sternotomy, with its better exposure and greater latitude for concomitant procedures, is preferred. PMID- 17723818 TI - Long-term outcomes after coronary artery bypass grafting: preoperative kidney function is prognostic. AB - OBJECTIVE: End-stage renal disease is an independent predictor of mortality after coronary artery bypass grafting. Limited information exists, however, regarding the impact of chronic kidney disease on long-term outcome after bypass grafting. The purpose of this study was to assess the impact of kidney function on long term outcomes in patients undergoing coronary artery bypass grafting. METHODS: We studied 931 consecutive patients undergoing coronary artery bypass grafting in a single center. Demographic and clinical data were collected preoperatively. Chronic kidney disease was defined preoperatively according to the Modification of Diet in Renal Disease equation as an estimated glomerular filtration rate less than 60 mL x min(-1) x 1.73 m(-2). Multivariate Cox proportional hazard analyses were performed to determine the independent prognostic factors after bypass grafting. The primary outcome was a composite, combining death, acute coronary syndrome, stroke or transient ischemic attack, and coronary or peripheral revascularization during follow-up. Secondary outcomes were overall causes of death and cardiovascular death, acute coronary syndrome, and stroke or transient ischemic attack. RESULTS: One hundred fourteen (12.2%) patients had preoperative chronic kidney disease (estimated glomerular filtration rate range, 20.5-59.8 mL x min(-1) x 1.73 m(-2)). After a mean follow-up of 3.1 +/- 1.4 years (median, 3.3 years), chronic kidney disease was found to be an independent predictor of the composite outcome (hazard ratio and 95% confidence interval, 1.46 [1.01-2.11]; P = .0467) and overall death (hazard ratio and 95% confidence interval, 1.89 [1.16 3.07]; P = .0106). CONCLUSIONS: Beyond the perioperative period, preoperative moderate-to-severe chronic kidney disease is an independent long-term predictor of cardiovascular events and total mortality after coronary artery bypass grafting. Chronic kidney disease status should be incorporated into prediction models and clinical risk assessments. PMID- 17723819 TI - Impaired cerebral autoregulation distal to carotid stenosis/occlusion is associated with increased risk of stroke at cardiac surgery with cardiopulmonary bypass. AB - OBJECTIVES: Severe carotid stenosis and occlusion are associated with an increased risk of stroke during and after cardiac surgery with cardiopulmonary bypass. Relevance of an impaired cerebral autoregulation caused by stenosis/occlusion is unknown. METHODS: We prospectively assessed the incidence of stroke in relation to severity of carotid disease and corresponding autoregulatory reserve in 2797 patients who had coronary artery bypass graft and/or valve surgery with cardiopulmonary bypass. Patients underwent preoperative carotid sonography and, in case of severe extracranial disease, transcranial Doppler sonography with carbon dioxide stimulation to assess cerebrovascular reserve capacity. RESULTS: Sixty-seven (2.4%) patients had an ischemic stroke, which was fatal in 5. Anterior hemispheric stroke occurred in 42 (1.9%) patients with no/low-grade stenosis, 6 (1.8%) with medium-grade stenosis, 1 (0.6%) with high-grade stenosis/occlusion and normal autoregulation, and 3 (27.3%) with high grade stenosis/occlusion and exhausted autoregulatory reserve. Increased risk was observed in patients with high-grade stenosis/occlusion and exhausted autoregulatory reserve also after adjustment for potential confounders (adjusted odds ratio [OR] 28.3, 95% confidence interval [CI] 5.8-139.1). Stroke risk was not increased in patients with stenosis/occlusion and normal autoregulation (1.5%, adjusted OR 0.6, 95% CI 0.2-1.6). CONCLUSIONS: Cerebrovascular reserve capacity evaluated by preoperative transcranial Doppler carbon dioxide testing is a major determinant of stroke risk in patients with carotid artery stenosis/occlusion undergoing cardiac surgery with cardiopulmonary bypass. Its assessment facilitates identification of patients with an excess perioperative stroke risk. PMID- 17723821 TI - Usefulness of microsimulation to translate valve performance into patient outcome: patient prognosis after aortic valve replacement with the Carpentier Edwards supra-annular valve. AB - OBJECTIVE: Numerous reports have been published documenting the results of aortic valve replacement. It is often not easy to translate these outcomes involving the condition of the valve into the actual consequences for the patient. We previously developed an alternative method to study outcome after aortic valve replacement that allows direct estimation of patient outcome after aortic valve replacement: microsimulation modeling. The goal of this article is to provide insight into microsimulation methodology and to give an overview of the advantages and disadvantages of simulation methods (in particular microsimulation) in comparison with standard methods of outcome analysis. METHODS: By using a primary dataset containing 1847 patients and 14,429 patient years, advantages and disadvantages of standard methods of outcome analysis are discussed, and the potential role of microsimulation is illustrated by means of a step-by-step explanation of building, testing, and using such a model. RESULTS: Total life expectancy, event-free life expectancy, and reoperation-free life expectancy for a 65-year-old male patient were 10.6 years, 9.2 years, and 9.8 years, respectively. Lifetime risk of reoperation due to structural valve deterioration was 13.3%. CONCLUSIONS: Microsimulation is capable of providing accurate estimates of age-related life expectancy and lifetime risk of reoperation for patients who underwent aortic valve replacement with the Carpentier-Edwards supra-annular valve. It provides a useful tool to facilitate and optimize the choice for a specific heart valve prosthesis in a particular patient. PMID- 17723820 TI - Patient-prosthesis mismatch after mitral valve replacement: myth or reality? AB - OBJECTIVE: Determining the risk of patient-prosthesis mismatch after mitral valve replacement is still controversial. In this study, we aimed to clarify incidence and clinical implications of such a complication. The accuracy of preoperative prediction of patient-prosthesis mismatch using published in vitro hemodynamic parameters was also investigated. METHODS: Ninety-two patients who underwent mitral valve replacement and received Carpentier-Edwards stented bioprosthesis (Edwards Lifesciences, LLC, Irvine Calif) were enrolled. Hemodynamic performances were evaluated at discharge, and the incidence of in vivo patient-prosthesis mismatch (indexed effective orifice area < or =1.2 cm2/m2) was evaluated. Correlation between in vivo patient-prosthesis mismatch and predicted patient prosthesis mismatch, based on previously published in vitro hemodynamic parameters, was also investigated. RESULTS: Five patients died within 30 days of the operation (5.4% mortality). Mean prosthesis size was 29.8 +/- 2. Mean postoperative effective orifice area and indexed effective orifice area (2.5 +/- 0.8 cm2 and 1.5 +/- 0.4 cm2/m2, respectively) compared favorably with those predicted in vitro (2.2 +/- 0.7 cm2 and 1.3 +/- 0.5 cm2/m2, respectively). In the subgroup of patients receiving prosthesis size of 27 or smaller, the difference reached statistical significance (2.47 +/- 0.83 and 1.61 +/- 0.7 for postoperative and predicted effective orifice areas, respectively; P < .001). Postoperative patient-prosthesis mismatch was recorded in 8 patients (8.6%), comparing favorably with the predicted patient-prosthesis mismatch (39% for overall population and 80% for patients receiving prosthesis size < or = 27). No significant correlation between size of prosthesis and early hemodynamic and clinical outcomes was shown. CONCLUSIONS: In our study, stented mitral bioprostheses showed satisfactory postoperative hemodynamic performance, even in smaller prosthesis sizes (< or =27 mm). Risk of in vivo postoperative patient prosthesis mismatch seems to be less relevant than preoperative risk prediction based on in vitro data. Further studies are needed to evaluate the potential clinical impact of mitral patient-prosthesis mismatch. PMID- 17723822 TI - Feasibility, safety, and efficacy of totally endoscopic coronary artery bypass grafting: multicenter European experience. AB - OBJECTIVE: The invention of robotic systems has begun a new era of endoscopic cardiac surgery. Reports on totally endoscopic coronary artery bypass grafting are limited, however, and data regarding feasibility, safety, and efficacy are needed to determine this technique's position in the therapeutic armamentarium. This study describes the largest multicenter experience in the literature with robotic totally endoscopic coronary artery bypass grafting specifically addressing procedural feasibility, safety, and efficacy. METHODS: Between September 1998 and November 2002, a total of 228 patients with coronary artery disease were scheduled for totally endoscopic coronary artery bypass grafting with the da Vinci Surgical System (Intuitive Surgical Inc, Sunnyvale, Calif.) at five European institutions. Patients underwent totally endoscopic coronary artery bypass grafting with either an on-pump (group A, n = 117) or an off-pump approach (group B, n = 111). Patients underwent postoperative angiography or stress electrocardiography and were followed up for 6 months. RESULTS: Procedural feasibility was demonstrated through the completion of 164 successful totally endoscopic cases. Sixty-four patients (group C, 28%) had conversion to nonrobotic procedures. Conversion rates decreased with time. The overall procedural efficacy, as defined by angiographic patency or lack of ischemic signs on stress electrocardiography, was 97%. The incidence of major adverse cardiac events within 6 months was 5%. CONCLUSION: Both on- and off-pump totally endoscopic coronary artery bypass grafting are feasible, with a conversion rate that diminishes with increasing experience. Conversion does not adversely affect outcome and thus constitutes a safe alternative. Although target vessel reintervention may be slightly higher than that reported for open coronary artery bypass grafting, graft patency and major adverse cardiac events for both approaches are comparable to those reported in the Society of Thoracic Surgeons database, demonstrating the safety and efficacy of the totally endoscopic coronary artery bypass grafting procedure. PMID- 17723823 TI - The multi-purse string maze procedure: a new surgical technique to perform the full maze procedure without atriotomies. AB - OBJECTIVE: The maze procedure is the most effective surgical procedure for atrial fibrillation. In recent years, a number of different surgical ablation devices were introduced and gradually replaced the need for the procedure to be performed by using the cut-and-sew technique. In this article a new surgical approach is presented using a full maze IV lesion set, without atriotomies. METHODS: Between January 2005 and June 2006, 12 patients underwent operations with the multi-purse string technique: 9 patients as a combined procedure with coronary artery bypass grafting, 2 patients as a combined procedure with aortic valve replacement, and 1 patient as a standalone procedure. In 5 additional patients, a small left atrial atriotomy was required to ensure the completeness of the mitral valve isthmus lesion. A combination of bipolar radiofrequency and cryothermal energies was used in all cases. All patients were part of our comprehensive follow-up and local atrial fibrillation registry. RESULTS: No perioperative morality, cerebrovascular accidents/transient ischemic attacks, or both were documented in this series. In a mean follow-up of 13 +/- 6 months, 1 late death was documented, and 91% of the patients are free from atrial fibrillation or flutter. CONCLUSIONS: Our experience suggests that the maze IV procedure can be performed without the need for atriotomies by using the multi-purse string approach. The intermediate results are promising, with high rates of success in ablating atrial fibrillation. Future studies should be performed to validate the safety of the use of bipolar radiofrequency devices endocardially on a beating heart. PMID- 17723824 TI - Trial of new vascular clips for aortic anastomosis in a canine model. AB - OBJECTIVES: We created a new vascular clip designed for aortic surgery. The purposes of this investigation were to examine surgical applicability in a clinically relevant aortic replacement model and to assess biomechanical strength of the clipped anastomosis and serial histologic changes in the clipped anastomotic site. METHODS: Twenty-one beagles underwent descending thoracic aortic replacement. Distal anastomosis was performed with the new clips, mimicking the cuffed anastomosis technique, and proximal anastomosis was carried out by conventional suture anastomosis. Tissue specimens of the anastomotic sites were harvested at 1, 3, 6, and 12 months postoperatively for examination. RESULTS: There was no significant difference in the time required to carry out clip anastomosis (12.2 +/- 1.3 minutes) and suture anastomosis (13.7 +/- 0.9 minutes; P = .38). Neither type of anastomotic site was disrupted by raising the intraluminal pressure to 280 mm Hg. Microscopically, the areas of aortic wall compressed by vascular clips appeared as hyalinized areas adjacent to surrounding collagen fibers, with no significant infiltration of inflammatory cells. Identical histologic changes were observed at the site of the sutured anastomosis. The media at the clipped anastomosis site was significantly thinner than that at the sutured anastomosis site at 1 month after the operation. However, there was no significant difference in the thickness of the media at 3 months. CONCLUSIONS: The new vascular clips were effective in this clinically relevant model, with appropriate biomechanical strength, and the anastomotic sites underwent similar histologic changes to those observed after suture anastomosis. PMID- 17723825 TI - Surgical atrial septal defect closure after interventional occluder placement: incidence and outcome. AB - OBJECTIVE: Closure of ostium secundum atrial septal defects is generally performed by using an interventional approach. We evaluated the outcome of patients requiring secondary surgical therapy. METHODS: From September 1996 until December, 2005, 418 patients received interventional and 297 patients underwent surgical closure of an ostium secundum atrial septal defect at our center. Another 15 patients (local, 5; regional, 5; and national, 5 referrals) had complications after occluder placement, and they form the study population. RESULTS: Indications for surgical repair in these 15 patients were dislocation of the occluder in 5, neurologic events after occluder placement in 5, residual defects in 4, and sepsis with questionable occluder infection in 1 patient. A total of 7 patients had neurologic events, 5 of embolic origin. The interval between interventional occluder placement and definitive surgical repair was 319 +/- 416 days (median 123 days; range 0-1395 days). Patient age at operation was 34.9 +/- 18.6 years. Nine patients were operated on via an anterolateral minithoracotomy, and 6 received a conventional sternotomy. One patient with sepsis underwent abdominal surgery on postoperative day 1 and subsequently died of multiorgan failure; there was no proof of occluder endocarditis. At 2.2 +/- 1.9 years of follow-up, all other patients had returned to full-time work without residual neurologic impairment. CONCLUSIONS: Complications may arise after interventional ostium secundum atrial septal defect closure. This must be evaluated against the extremely low risk of a standard surgical closure. The functional outcome after secondary surgical ostium secundum atrial septal defect closure with removal of an occluder system is excellent. PMID- 17723827 TI - Coarctation Long-term Assessment (COALA): significance of arterial hypertension in a cohort of 404 patients up to 27 years after surgical repair of isolated coarctation of the aorta, even in the absence of restenosis and prosthetic material. AB - OBJECTIVE: Recent studies have demonstrated that there is a loss of aortic compliance in patients after coarctation repair. The clinical effect of this and other mechanisms apart from restenosis on the rate of arterial hypertension is unknown. METHODS: From 1974 through 2000, 404 patients born before January 1, 1985, underwent surgical intervention for isolated aortic coarctation. From those 382 who are still alive, 273 patients aged 16 to 73 years (1-27 years after surgical intervention) underwent a structured clinical investigation according to a prospective protocol, including blood pressure measurement at all limbs, ambulatory blood pressure measurement, and symptom-limited exercise testing. RESULTS: Sixty-seven (25%) patients were already taking antihypertensive drugs, and another 63 (23%) patients had an increased ambulatory blood pressure. Still another 26 (10%) patients had a blood pressure during exercise exceeding 2 standard deviations of reference values. Only 117 (43%) patients had a normal blood pressure reaction. From those 156 patients with hypertension, only 21 (13%) had a systolic brachial-ankle blood pressure difference of greater than 20 mm Hg, suggesting restenosis. In the patient group without restenosis (n = 245), independent risk factors for hypertension were repair with prosthetic material, male sex, a residual brachial-ankle blood pressure difference, and older age at follow-up. CONCLUSIONS: The majority of patients were hypertensive at long-term follow-up after coarctation repair. This is caused by restenosis, defined by a gradient of greater than 20 mm Hg, in only a few patients. Even in those without prosthetic material or minimal-grade restenosis, there is a substantial incidence of arterial hypertension. PMID- 17723828 TI - Utility of intravenous catheters for femoral arterial cannulation in infants having complicated sternal re-entry. AB - OBJECTIVE: Many children undergoing surgery for congenital heart disease have had prior operations. Reoperative sternotomy carries with it the risk of cardiac injury and the need for emergency peripheral cannulation. Unfortunately, in smaller children, many of the standard sites are occluded, stenosed, or too small for the smallest manufactured cannulas. Using a model, we evaluated the feasibility of using peripheral intravenous catheters for establishing cardiopulmonary support. METHODS: A model cardiopulmonary bypass circuit was created. Catheters of varying diameter and length were used to simulate arterial cannulation. With each catheter, flows were incrementally increased until a maximum arterial line pressure was achieved. Data were recorded. RESULTS: Catheter diameters increased from 24 to 14 gauge, and catheter lengths increased from 1 inch to 1.88 inches. Flow could not be established through the 24-gauge catheter without an unacceptably high arterial line pressure. From the next smallest catheter (22 gauge x 1 inch) to the largest catheter (14 gauge x 1.88 inches), maximum achievable flow rates ranged from 70 to 540 mL/min, respectively. CONCLUSIONS: Peripheral arterial cannulation may be lifesaving in cases of complicated sternal re-entry in children. Intravenous catheters can be used when vessels are too small for standard cannulas. Flow rates that provide adequate support while maintaining acceptable arterial line pressures are achievable with peripheral intravenous catheters until central cannulation can be accomplished safely. PMID- 17723829 TI - Replacement of the systemic atrioventricular valve with a mechanical prosthesis in children aged less than 6 years: late clinical results of survival and subsequent replacement. AB - OBJECTIVE: We analyzed the survival, clinical course, and role of prosthesis patient mismatch after systemic atrioventricular valve replacement in children. METHODS: From 1974 to 2006, 69 patients underwent systemic atrioventricular valve replacement (median age 1.2 years, range 1.1 months to 5.4 years), with 17 patients requiring re-replacement of the systemic atrioventricular valve. Prosthesis-patient relationship was analyzed by comparing (1) the prosthetic valve diameter and the predicted annulus diameter based on the body surface area and (2) the prosthetic valve diameter and the measured annulus diameter. RESULTS: Survival was 73% at 1 year and 65% at 5, 10, and 15 years. Age, weight, body surface area, predicted annulus diameter, prior surgery, underlying disease, and ratio of prosthetic valve diameter to body weight were significant predictors of death. Variables associated with re-replacement of the systemic atrioventricular valve were body surface area, prosthetic valve diameter, predicted annulus diameter, and presence of multiple left-sided obstructive lesions. The majority of patients received a prosthesis larger than the predicted annulus diameter. There was good correlation between the prosthetic valve diameter and the measured annulus diameter (r = 0.85). Mismatch, as described by the difference in z scores of prosthetic valve diameter and measured annulus diameter, was not a significant predictor of death or re-replacement of the systemic atrioventricular valve. CONCLUSIONS: Although valve replacement is considered the last therapeutic option after failed attempts of valvuloplasty, long-term outcome is favorable. Selection of the prosthesis is made on the basis of the measured annulus diameter. An elevated ratio of prosthetic valve diameter to body weight is associated with patients with low body weight or a large native annulus in dilated ventricles. PMID- 17723830 TI - Evolution of surgical techniques for atrial septal defect repair in adults: a 10 year single-institution experience. AB - OBJECTIVE: We retrospectively analyzed our experience in atrial septal defect repair with varied minimally invasive surgical approaches. METHODS: From 1997 to 2006, 64 patients underwent surgical repair of atrial septal defects in our center. Patients were grouped into four groups according to the approach used; group 1 (n = 16), partial lower sternotomy; group 2 (n = 20), right anterior small thoracotomy with transthoracic clamping; group 3 (n = 4), right anterior small thoracotomy with endoaortic balloon clamping; and group 4 (n = 24), totally endoscopic approach with the use of the da Vinci surgical system (Intuitive Surgical, Mountain View, Calif). Preoperative diagnosis was a large secundum type atrial septal defect in 60 patients, primum type in 3 patients, and sinus venosus type in 1 patient. RESULTS: Complete atrial septal defect closure was verified by intraoperative transesophageal echocardiography in all patients. There was neither perioperative mortality nor major complication. Groups 3 and 4 had significantly longer aortic crossclamp, cardiopulmonary bypass, and skin-to-skin operative times than had groups 1 and 2 (P = .000). All groups had similar ventilation time, postoperative drainage, and intensive care unit and hospital stays. Only 2 patients in group 4 were converted to the minithoracotomy owing to endoaortic balloon failure. During the follow-up of 30 +/- 24.3 months, 1 patient in group 3 was reoperated on owing to significant residual shunting. CONCLUSIONS: All types of atrial septal defects can be repaired via those four different approaches as safely as can be done by the conventional technique. General complications during surgical procedures are negligible. These approaches may be considered a standard treatment and an adjunct to transcatheter treatment options in atrial septal defect repair. PMID- 17723831 TI - Determinants of early outcome after neonatal cardiac surgery in a developing country. AB - OBJECTIVE: Significant technologic advances have improved outcomes in neonatal cardiac surgery over the past 3 decades. However, outcomes might be different in developing countries with resource limitations. We sought to identify the determinants of early outcome after neonatal cardiac surgery in a tertiary referral center in South India. METHODS: Hospital records of 330 consecutive neonates who underwent surgical intervention between January 1999 and April 2006 were reviewed, and perioperative variables were recorded. Main outcome measures were 30-day mortality, postoperative bloodstream infection, and hospital stay of longer than 10 days. Multivariate logistic regression analysis was performed. RESULTS: Overall mortality was 8.8%. Mortality significantly decreased from 21.4% before 2002 to 4.3% after 2002 (3.2% for corrective operations, P < .0001). The prevalence of postoperative bloodstream infection remained the same, whereas surgical site infection and hospital stay significantly increased after 2002. Predictors of outcomes on multivariate analysis were as follows: (1) mortality- operation before 2002 (odds ratio, 5.5), age less than 7 days (odds ratio, 3.8), preoperative antibiotic use (odds ratio, 5.6), and postoperative exchange transfusion (odds ratio, 14.9); (2) postoperative bloodstream infection (21.2%)- use of cardiopulmonary bypass (odds ratio, 2.0), reintubation (odds ratio, 7.7), and surgical site infection (odds ratio, 4.1); and (3) hospital stay of longer than 10 days (61.2%)--use of cardiopulmonary bypass (odds ratio, 2.8), delayed sternal closure (odds ratio, 3.6), reintubation (odds ratio, 12.1), surgical site infection (odds ratio, 13.8), and postoperative antibiotic use (odds ratio, 4.4). CONCLUSIONS: With increasing experience, neonatal cardiac surgery can be performed with excellent outcomes in developing countries with resource limitations. Infectious complications contribute significantly to morbidity and mortality, and improvements in infection-control practices should be emphasized to improve outcomes further. PMID- 17723832 TI - Two-year general and neurodevelopmental outcome after neonatal complex cardiac surgery in patients with deletion 22q11.2: a comparative study. AB - OBJECTIVE: Neonatal complex cardiac surgery carries a significant risk for adverse neurodevelopmental outcome. We hypothesized this risk to be higher in patients with deletion 22q11.2. METHODS: From 1996 to 2004, neonates who had complex cardiac surgery at age 6 weeks or less had multisite, multidisciplinary health and neurodevelopmental outcomes (Bayley Scales of Infant Development II; mental and psychomotor developmental indices [MDI, PDI] as mean [SD] and delay [<70]) assessed at 18 to 24 months of age. All 16 patients with deletion 22q11.2 (group 1) were compared with 16 patients without deletion 22q11.2 (group 2) having undergone neonatal complex cardiac surgery at the same center and matched for cardiac lesion, socioeconomic status, and year of operation. Outcomes were compared by univariate and multivariate analyses. RESULTS: Heart lesions in each group consisted of 6 (37.5%) cases of interrupted aortic arch, 6 (37.5%) cases of truncus arteriosus, and 4 (25%) cases of tetralogy of Fallot. Outcomes were available for all survivors. Mortality was 3 (19%) and 1 (6%) in groups 1 and 2, respectively (P = .6). MDI and PDI scores were 66.1 (10.6) and 55.0 (9.4) for group 1 and 86.3 (14.6) and 82.3 (14.3) for group 2 (P < .001). Only deletion 22q11.2 was significant in stepwise multiple regression to predict MDI and PDI scores. Mental delay occurred in 8 (61.5%) of 13 in group 1 and 2 (13.8%) of 15 in group 2 (P = .016). Psychomotor delay occurred in 11 (84.6%) of 13 in group 1 and 1 (6.7%) of 15 in group 2 (P < .001). CONCLUSION: Neonates affected by deletion 22q11.2 and having neonatal complex cardiac surgery have significantly worse neurodevelopmental outcome than do those without deletion 22q11.2. PMID- 17723833 TI - Simvastatin attenuates cardiac isograft ischemia-reperfusion injury by down regulating CC chemokine receptor-2 expression. AB - OBJECTIVE: Accumulating evidence reveals that statins possess direct anti inflammatory properties through inhibition of proinflammatory cytokine and chemokine secretion in addition to their antioxidant effects, which may contribute to amelioration of ischemia-reperfusion injury. This study tested the hypothesis that perioperative treatment of simvastatin suppresses the cardiac isograft ischemia-reperfusion injury by down-regulation of CC chemokine receptor 2 expression in an inbred rat model of cardiac transplantation. METHODS: Donor hearts from Lewis rats were heterotopically transplanted to Lewis rat recipients. Recipients were orally treated with simvastatin (1 mg/kg) or vehicle every morning 3 days before the surgery until the harvest day. Rats were killed at 6 hours and at 1, 3, and 7 days after transplantation. Injury was assessed by infarct size measurement, histologic and immunohistochemical examination, and intragraft myeloperoxidase activity assay. Monocyte chemoattractant protein-1 levels in serum and graft were analyzed by enzyme-linked immunosorbent assay, and intragraft CC chemokine receptor-2 expression was measured by quantitative real time polymerase chain reaction. RESULTS: The infarct size and macrophage infiltration were all significantly reduced in the simvastatin-treated group compared with those of the control group at 1 day after transplantation. Neutrophil accumulation was significantly suppressed until 3 days after transplantation, whereas myeloperoxidase activity had been significantly diminished at 1 day after transplantation. Both monocyte chemoattractant protein 1 concentrations in serum and graft were remarkably decreased at 6 hours after transplantation. Intragraft CC chemokine receptor-2 expression was also down regulated at 1 day and 3 days after transplantation. CONCLUSIONS: Perioperative treatment of simvastatin could suppress the isograft ischemia-reperfusion injury through retarding intragraft monocyte chemoattractant protein-1 accumulation and CC chemokine receptor-2 expression. PMID- 17723834 TI - Relation of waveform of transit-time flow measurement and graft patency in coronary artery bypass grafting. PMID- 17723835 TI - Intermittent incomplete closure of Medtronic Advantage aortic valve leaflets causes unnecessary reoperation. PMID- 17723836 TI - Transaortic resection of an apical left ventricular fibroelastoma facilitated by a thoracoscope. PMID- 17723837 TI - Left atrial myxoma: the role of multisclice computed tomography. PMID- 17723838 TI - Pulmonary artery banding for idiopathic dilative cardiomyopathy: a novel therapeutic strategy using an old surgical procedure. PMID- 17723839 TI - Cell Saver device efficiently removes cell-derived microparticles during cardiac surgery. PMID- 17723841 TI - Anterior transclavicular approach to malignant tumors of the thoracic inlet: importance of the scapulothoracic articulation. PMID- 17723840 TI - Primary intrapulmonary thymoma associated with congenital hyperhomocysteinemia. PMID- 17723842 TI - Osteomalacia associated with a fibroblast growth factor-23 secreting chest wall tumor. PMID- 17723844 TI - Primary thoracic synovial sarcoma: factors affecting long-term survival. PMID- 17723843 TI - Staged closure of tracheogastrocutaneous fistula after esophagectomy for infiltrative granular cell tumor. PMID- 17723845 TI - Overt lymph node metastases from a gastrointestinal stromal tumor of the esophagus. PMID- 17723846 TI - Suppurative Salmonella thyroiditis coexistence with invasive thymoma. PMID- 17723847 TI - Lung transplantation in Kartagener syndrome and situs inversus: potential of multidetector row computed tomography and three-dimensional postprocessing. PMID- 17723848 TI - Comparing, by means of a meta-analytic approach, the available evidence on off pump coronary artery bypass surgery (OPCABG) with percutaneous coronary intervention (PCI). PMID- 17723850 TI - Fixed subaortic stenosis. PMID- 17723851 TI - Familial recurrence of discrete membranous subaortic stenosis. PMID- 17723852 TI - Bovine jugular vein as aortic enlargement patch in the Norwood procedure. PMID- 17723853 TI - Improved saphenous vein graft patency for coronary artery bypass grafting: "no touch" harvesting or "dissection without touching"? PMID- 17723856 TI - Conservative management of postintubation tracheobronchial ruptures. PMID- 17723858 TI - A segmentectomy for stage IA non-small cell lung cancer should be associated with surgical margin cytology findings and a frozen section histologic examination of lymph nodes. PMID- 17723860 TI - The sinuses of valsalva: they should be anatomically correct and physiologically compliant. PMID- 17723861 TI - If older donors are acceptable, then older recipients should also be acceptable. PMID- 17723864 TI - Independent lung ventilation in adult single-lung transplantation: is it time for fast-track anesthesia and early tracheal extubation? PMID- 17723866 TI - Iatrogenic coronary stenosis. PMID- 17723868 TI - Performance-enhancing substances: is your adolescent patient using? AB - Small, but significant, numbers of adolescents use anabolic-androgenic steroids to improve their appearance or sports performance. Many more use creatine and other performance-enhancing substances with the hope of achieving these goals. This article assists primary care physicians in the office assessment of adolescents who may be using these substances, focusing on identifying adolescents at risk, asking the right questions, and helping adolescents feel comfortable discussing this sensitive topic. Providers must present themselves as credible sources of information on the topic to communicate effectively with adolescent athletes. PMID- 17723869 TI - Prevalence of use of performance-enhancing substances among United States adolescents. AB - Adolescents may regard the use of performance-enhancing substances as an easy means to gain self-esteem through improved body appearance and athletic performance. The use of performance-enhancing substances by adolescents is particularly troubling because safety data are largely lacking. This poses a dilemma for the pediatrician who needs correct information, including the potential efficacy and negative health effects of such substances, to identify the patients in need of counseling and to find the best way to help adolescent patients make informed decisions to promote healthy behaviors. This article is intended to assist pediatricians by providing a summary of the current state of knowledge regarding the prevalence of use of performance-enhancing substances by United States adolescents. PMID- 17723870 TI - Consequences of use of anabolic androgenic steroids. AB - Whether providing anticipatory guidance to the young adolescent patient, conducting a preparticipation examination on a young athlete, or treating a sick user of anabolic androgenic steroids (AASs), the primary care physician must be familiar with the adverse consequences of the use of these compounds. This article reviews the endocrine, cardiovascular, neuropsychiatric, musculoskeletal, hematologic, hepatic, and miscellaneous effects of AASs, highlighting effects reported in children and adolescents, and relying on consequences in adults when pediatric data is unavailable. PMID- 17723871 TI - Erythropoietin and other blood-boosting methods. AB - Dating back to the earliest Olympics, athletes have been searching for a performance edge. Recombinant human erythropoietin was made commercially available in 1987 to treat various diseases associated with anemia. Within a few years, elite endurance athletes capitalized on its potential as an undetectable performance-enhancing agent. Although antidoping agencies have developed a test to detect its use, there are pitfalls. More importantly, athletes continue to add more sophisticated doping practices to their armamentarium, challenging regulatory agencies, putting their health at great risk, and tainting the spirit of fair competition. PMID- 17723873 TI - Beyond sports-doping headlines: the science of laboratory tests for performance enhancing drugs. AB - This primer on urine analysis in sports-doping control is an overview with an emphasis on the main analytical chemistry technologies in use: gas chromatography mass spectrometry (GC-MS), liquid chromatography-tandem mass spectrometry (LC-MS MS), isotope ratio mass spectrometry detection of exogenous testosterone use, and isoelectric focusing detection of recombinant erythropoietin (EPO) use. Included are graphic examples of GC-MS selected ion monitoring and full scan, LC-MS-MS, and EPO test electropherogram data; a list of common acronyms; and answers to questions frequently asked about tampering and test accuracy. PMID- 17723872 TI - The world anti-doping program and the primary care physician. AB - The presence of a prohibited substance in an athlete's urine (or blood, when applicable) or the use of a prohibited method constitutes a doping offense, even if the substance is a pharmaceutical and is properly prescribed. To avoid a doping offense for the therapeutic use of a prohibited substance or method the International Standard for Therapeutic Use Exemptions (TUE) must be followed. When the TUE is required, the appropriate process must be completed before testing under conditions where the substance or method is prohibited. This article describes the World Anti-Doping Code and the International Standards, which are part of the Code. In addition, the procedures for the proper preparation and submission of TUE requests are presented along with the manner in which the requests are considered by the Therapeutic Use Exemption Committees. PMID- 17723874 TI - Creatine and other supplements. AB - Ergogenic dietary supplement use is highly prevalent among adolescent and collegiate athletes, and use is increasing. To make appropriate recommendations for or against use by individual athletes, physicians who work with adolescent athletes should be knowledgeable about the most commonly used supplements and be able to access high-quality information about others. This article first discusses the legal and regulatory environment of dietary supplements. Several of the most commonly used supplements are then discussed in detail, including creatine, beta-hydroxy-beta-methylbutyrate, protein, amino acids, stimulants, alkalotic agents, glycerol, vitamins, and minerals. Finally, the "Gateway Theory" as it may relate to adolescent supplement and other drug use is discussed. PMID- 17723875 TI - The history of the development of anabolic-androgenic steroids. AB - The history of anabolic-androgenic steroids (AASs) is an interesting tale that has its roots in ancient "endocrinology." More than 6000 years ago, farmers noted enhanced domestication of animals after castration. The development of AASs, and, later, their artificial synthesis, have remained a hot topic in scientific research and pharmaceuticals. Over the years, AASs have been used as a proposed treatment for a wide variety of ailments, despite deleterious side effects. Unfortunately, they have been, and still are, abused by body builders, athletes, and teens. PMID- 17723876 TI - Anabolic-androgenic steroids: use and abuse in pediatric patients. AB - The "win at all costs" mentality fuels athletes to seek performance-enhancing substances, such as anabolic-androgenic steroids, to gain an advantage over their opponents. Nonathletes espouse this same attitude to "win" the battle of attractiveness. An enhanced understanding of anabolic-androgenic steroids and the motivations behind their abuse will arm pediatricians with the ability to engage their patients in a balanced discussion of the benefits and costly risks of anabolic-androgenic steroids and successfully deter further use. PMID- 17723877 TI - Testosterone precursors: use and abuse in pediatric athletes. AB - The dietary supplements androstenedione, dehydroepiandrosterone, and androstenediol are precursors in the endogenous production of testosterone. The efficacy and safety of these prohormones are not well established but are promoted to have the same androgenic effects on building muscle mass and strength as anabolic-androgenic steroids. Studies have demonstrated repeatedly that acute and long-term administration of these oral testosterone precursors does not effectively increase serum testosterone levels and fails to produce any significant changes in lean body mass, muscle strength, or performance improvement compared with placebo. The Anabolic Steroid Control Act of 2004 lists androstenedione as a schedule III controlled substance, and it is regulated by the U.S. Food and Drug Administration. Testosterone precursors are banned by most major sports organizations. PMID- 17723878 TI - Sports medicine: performance-enhancing drugs. AB - Performance-enhancing drugs, ergogenic aids, or sports supplements have been a part of sports since sporting competition began and likely always will be. Considered cheating by purists and necessary by some athletes, we must accept the fact that they are used, understand why they are used, and study how to prevent their use to institute change. This article summarizes current information regarding the use of performance-enhancing drugs in young athletes and provides proven prevention strategies for instituting a program in your local schools. PMID- 17723879 TI - Gene doping: a review of performance-enhancing genetics. AB - Unethical athletes and their mentors have long arrogated scientific and medical advances to enhance athletic performance, thus gaining a dishonest competitive advantage. Building on advances in genetics, a new threat arises from athletes using gene therapy techniques in the same manner that some abused performance enhancing drugs were used. Gene doping, as this is known, may produce spectacular physiologic alterations to dramatically enhance athletic abilities or physical appearance. Furthermore, gene doping may present pernicious problems for the regulatory agencies and investigatory laboratories that are entrusted to keep sporting events fair and ethical. Performance-enhanced genetics will likewise present unique challenges to physicians in many spheres of their practice. PMID- 17723880 TI - Abuse of growth hormone among young athletes. AB - The underground abuse of growth hormone (GH) among young athletes presents a challenge to medical professionals. Health care professionals providing knowledgeable guidance regarding healthy ways to improve performance and appearance, as well as accurate information regarding substances' perceived benefits, risks, and unknown qualities, is invaluable to the young athlete. Further research focused on the profile and motivation of young people who use GH is essential to understanding and intervening better with those who use these substances. PMID- 17723881 TI - Correlation between preoperative biliary drainage, bile duct contamination, and postoperative outcomes for pancreatic surgery. AB - BACKGROUND: Although previously examined, the potential relationship between preoperative biliary drainage (PBD), intraoperative bile culture (IBC), and postoperative morbidity and mortality rate for pancreatic surgery remains unclear. METHODS: Two hundred twenty patients underwent operation for either benign pancreatic disease or malignant periampullary and pancreatic neoplasms, consisting of pylorus-preserving proximal pancreatoduodenectomy (n = 180), biliary bypass (n = 31), and total pancreatectomy (n = 9). An intraoperative bile specimen was prospectively collected immediately after division of the bile duct and sent for bacteriologic evaluation for both aerobic and anaerobic microorganisms. Morbidity and mortality rates were evaluated. RESULTS: Of 220 patients evaluated, 113 patients (51.4%) had a positive IBC. Factors associated with a positive IBC were age >70 years (odds ratio [OR], 5.9;95% confidence interval, [CI]: 1.6-22.1; P = .007), history of coronary artery disease (OR, 0.08; 95% CI, 0.01-0.5; P = .007), diagnosis of neoplasia (OR, 0.3; 95% CI, 0.1 0.9; P =. 03), and PBD (OR, 0.1; 95% CI, 0.06-0.2; P = .0001). Infectious complications (OR, 1.8; 95% CI, 1-3; P = .03), and wound infection (OR, 2.8; 95% CI,1.4-5.3; P = .002) were greater in patients with positive IBC. CONCLUSIONS: PBD predisposes to a positive IBC. Patients with a positive IBC have a clinically important increased risk of developing both infectious complications and wound infection after pancreatic surgery. PMID- 17723882 TI - Serum interleukin-15 level is a useful predictor of the complications and mortality in severe acute pancreatitis. AB - BACKGROUND: In severe acute pancreatitis, multiple organ dysfunction syndrome and infectious complications are contributors to high mortality. Interleukin (IL)-15 is a novel cytokine that shares many biologic properties with IL-2. Serum IL-15 levels have not yet been determined in SAP. METHODS: Serum IL-15 concentrations were measured in 54 patients with severe acute pancreatitis on admission. The relationships with severity, organ dysfunction, infection, and prognosis were analyzed. Utility of IL-15 for the prediction of clinical outcome was evaluated by receiver operator characteristic (ROC) curve analysis. RESULTS: Serum IL-15 levels were increased significantly in severe acute pancreatitis (5.8 +/- 0.5 pg/mL), and they were correlated with Ranson, APACHE II, and Japanese severity score. Serum IL-15 levels were greater in patients with organ dysfunction, patients with infection, and nonsurvivors (P < 05 each). Incidences of organ dysfunction in patients whose IL-15 levels were less than 3.0, 3.0-5.3, and greater than or equal to 5.3 pg/mL, were 8%, 31%, and 89%, respectively (P < .001). Usefulness of IL-15 for the prediction of organ dysfunction was superior to CRP, IL-6, and IL-8, and it was similar to Ranson, APACHE II, and Japanese severity score. Incidences of infection in patients whose IL-15 levels were less than 5.5, 5.5-9.0, and greater than or equal to 9.0 pg/mL, were 7%, 25%, and 50%, respectively (P < .05). Mortality rates in patients whose IL-15 levels were less than 5.5, 5.5-9.0, and greater than or equal to 9.0 pg/mL, were 11%, 25%, and 80%, respectively (P < .001). Usefulness of IL-15 for the prediction of death was superior to CRP, IL-6, and IL-8. CONCLUSIONS: Serum IL-15 level is a useful predictor of the complications (especially organ dysfunction) and mortality in severe acute pancreatitis. PMID- 17723883 TI - Enterokinase induces severe necrosis and rapid mortality in cerulein pancreatitis: characterization of a novel noninvasive rat model of necro hemorrhagic pancreatitis. AB - BACKGROUND: Unlike edematous pancreatitis, induction of severe necrotizing pancreatitis in rats generally requires an invasive laparotomy with infusion and/or ligation of the pancreatic duct or duodenal or arterial occlusion. The aim of this study was to establish and characterize a noninvasive model of severe acute pancreatitis in rats. METHODS: Wistar rats were infused intravenously with cerulein or a combination of cerulein and enterokinase. Saline (154-mmol/L NaCl) or enterokinase only was infused in controls. In a first set of experiments, intrapancreatic protease activation and the release of cytokines were correlated with the severity of organ injury. Pancreatic and pulmonary injuries were determined at 6 h. In a second set of experiments, we assessed 24-h survival, serum parameters possibly reflecting the course of the disease, and morphologic changes later in the course of the disease. RESULTS: The severity of pancreatic injury and survival were correlated strongly with the amount of enterokinase infused simultaneously with cerulein. Trypsin as well as elastase and cathepsin B activity in pancreatic tissue samples were increased markedly in these animals. Marked pancreatic hemorrhage, necrosis, and leukocyte infiltration were present in animals with the greatest amounts of enterokinase infused. IL-6 and LDH, but not IL-1beta, CRP, and amylase, in serum correlated with the severity of pancreatitis. CONCLUSIONS: This noninvasive rat model of acute pancreatitis is characterized by major pancreatic necrosis, hemorrhage, and fatality. The simple and noninvasive induction technique may have advantages for future studies on inflammatory changes and sepsis in necrotizing pancreatitis compared with other currently available invasive models. PMID- 17723884 TI - Early discharge after nonoperative management for splenic injuries: increased patient risk caused by late failure? AB - BACKGROUND: With increasing experience and knowledge about nonoperative management of splenic injury (NOMSI), patients are being discharged early and possibly placed at risk for late failure of NOMSI and its associated complications. To evaluate if blunt trauma patients managed by NOMSI can be safely discharged early, because failure after the third day from injury occurs infrequently and is not associated with added morbidity. METHODS: The medical records of patients who failed NOMSI from January 1993 to December 2005 in an academic level 1 trauma center were reviewed. Patients who failed NOMSI within 3 days (early failure) were compared with patients who failed it after 3 days (late failure) to identify characteristics that may help predict late failure. Primary outcomes were complications and death related to late failure. RESULTS: Of 691 patients admitted with blunt trauma to the spleen, 499 (72%) had NOMSI and 36 (7%) failed it. Early failure was recorded in 26 patients (5%) and late failure in 10 (2%). Late bleeding was the cause of failure in all patients with late failure and occurred in 8 +/- 6 (mean +/- SD) days after admission (4-8 days in 7 patients and 12-22 days in 3). When comparing age, Injury Severity Score, hemotocrit on admission, preoperative blood transfusions, and grade of splenic injury, no differences were found between patients with early and late failure. All but 1 patient with late failure were still in the hospital for associated injuries at the time of failure. No patient died, had delayed diagnosis, or suffered added morbidity because of late failure. CONCLUSION: Late failure occurs infrequently, unpredictably, and almost always in patients who are still in the hospital for associated injuries. In-hospital observation beyond the third day after injury is not necessary for most patients with splenic injury, who have no other reason to remain hospitalized. PMID- 17723886 TI - Targeting individual hemodynamics to maintain renal perfusion during pneumoperitoneum in a porcine model. AB - BACKGROUND: Although aggressive fluid hydration prevents a decrease in renal cortical perfusion (RCP) during laparoscopic donor nephrectomy, excess fluid is deleterious. We assessed whether goal-directed fluid administration, based on hemodynamic measures, would maintain RCP during pneumoperitoneum with less fluid loading. METHODS: In a pilot study of 7 pigs, goal-directed fluid administration was guided by monitoring of stroke volume (SV) by esophageal Doppler measurement. During 15 mmHg CO(2) pneumoperitoneum, a bolus of 5 mL/kg 0.9% NaCl was given when SV decreased to 90% of baseline. Next, 18 pigs were randomized into 3 groups: low fluid (5 mL/kg per hour), high fluid (25 mL/kg per hour) and goal directed. Urine output, heart rate, mean arterial pressure, cardiac output, SV, and RCP were recorded every 15 minutes. RESULTS: Pilot data revealed mean RCP (mL/min per 100 g) was maintained (40 vs 39) during pneumoperitoneum using goal directed therapy. In the randomized study, RCP was decreased in the low fluid group (43 vs 29; P= .02), but maintained in the high (46 vs 40) and goal-directed (42 vs 39) groups. Mean fluid administered in the goal-directed group during pneumoperitoneum was 10 mL/kg and only 3 of 6 of pigs required boluses. Urine output was decreased in all 3 groups. CONCLUSION: A goal-directed strategy during pneumoperitoneum allows for tailored fluid administration and maintains RCP with lower volumes of intravenous fluid. PMID- 17723885 TI - Environmental impact of accelerated clinical care in a high-volume center. AB - BACKGROUND: "Fast-track" surgery, involving multimodal care, improves efficiency and short-term outcomes in patients undergoing bowel resection. The sustainability of the benefits and the "drag" effect on non-participating surgeons through changed nursing and resident practice is undetermined. METHODS: 297 consecutive elective colon resections (DRG149) within three study periods (pre-change, immediate post-change, long-term post-change) were retrospectively reviewed. Two surgeons began to "fast-track" their patients in 1999 independently from the other surgeons in the hospital. Surgeons were grouped into "fast-track surgeons," "high-volume surgeons," (>/=10 cases per year) and "low-volume surgeons," (<10 cases per year). Comparisons of duration of stay (DOS), readmission rates, and mortality were made for each of three time periods and surgeon groups. Trends were also compared with unrelated hospital non-colectomy control groups (uncomplicated craniotomy DRG 001 and pancreatic surgery DRG 192) and to a colectomy control group from a statewide database (DRG 149). RESULTS: Mean DOS for colon resection significantly decreased among the "fast-track" surgeons and among all the other surgeons in the hospital, from 6.3 +/- 0.3 days, down to 3.7 +/- 0.1 days. We found no significant difference in mortality or readmission rates between the study periods. 15% of the cases were performed laparoscopically, and the improvements in outcome were independent of surgical technique. Control group analyses demonstrated that the environmental impact on outcome was independent of hospital-wide or regional improvement efforts. CONCLUSIONS: Implementation of a new practice pattern in a shared environment leads to improved outcomes for patients of other surgeons within the same environment. Dissemination and cross-pollination of new methods through resident, nurse, and case manager practice pattern modification creates a favorable force for change and this impact is sustained over a 3-year period. PMID- 17723887 TI - Peritoneal acidosis mediates immunoprotection in laparoscopic surgery. AB - BACKGROUND: We have shown previously that abdominal insufflation with CO(2) increases serum levels of IL-10 and TNFalpha and increases survival among animals with lipopolysaccharide (LPS)-induced sepsis, even after a laparotomy. We demonstrated previously that the effect of CO(2) is not from changes in systemic pH, although the peritoneum is locally acidotic during abdominal insufflation with CO(2) even when systemic pH is corrected. We hypothesized that acidification of the peritoneum via means other than CO(2) insufflation would produce alterations in the inflammatory response similar to those associated with CO(2) pneumoperitoneum. METHODS: In total, 42 rats were randomized into 7 groups (n = 6): 1) LPS only, 2) anesthesia control, 3) helium pneumoperitoneum, 4) CO(2) pneumoperitoneum, 5) buffered mild acid lavage, 6) buffered strong acid lavage, and 7) buffered strong acid lavage + helium pneumoperitoneum. Animals received anesthesia with vaporized isoflurane (except the LPS-only group) and their respective abdominal treatment (pneumoperitoneum and/or lavage) for 30 min followed immediately by stimulation with systemic LPS (1 mg/kg, IV). Blood was harvested via cardiac puncture 60 min after LPS injection, and serum levels of IL 10 and TNFalpha levels were determined by enzyme-linked immunosorbent assay. RESULTS: Mean peritoneal pH decreased (P < .05) after CO(2) pneumoperitoneum, buffered strong acid lavage, and buffered strong acid lavage + helium pneumoperitoneum, and it decreased (P = .1) after helium pneumoperitoneum alone and buffered mild acid lavage. IL-10 levels were increased (P < .01), and TNFalpha levels decreased (P < .001) among animals with acidic peritoneal cavities compared with animals with pH-normal peritoneal cavities. Decreasing peritoneal pH correlated with both increasing IL-10 levels (r = -.465, P < .01) and decreasing TNFalpha levels (r = 0.448, P < .01). Among animals with peritoneal acidosis, there were no differences in levels of IL-10 or TNFalpha regardless of insufflation status (P > .05 for both cytokines). CONCLUSIONS: Acidification of the peritoneal cavity whether by abdominal insufflation or by peritoneal acid lavage increases serum IL-10 and decreases serum TNFalpha levels in response to systemic LPS challenge. The degree of peritoneal acidification correlates with the degree of inflammatory response reduction. These results support the hypothesis that pneumoperitoneum-mediated attenuation of the inflammatory response after laparoscopic surgery occurs via a mechanism of peritoneal cell acidification. PMID- 17723888 TI - Biomechanical analyses of overlap and mesh dislocation in an incisional hernia model in vitro. AB - BACKGROUND: Incisional hernia repair is one of the most common surgical complications. Despite the introduction of mesh techniques of repair, recurrences are still prevalent. The aim of the current study was to evaluate the dependence of mesh dislocation on defect size, facial overlap, mesh-position, and orientation of the mesh in cases of anisotropic stretchability. METHODS: An in vitro incisional hernia model was used, which consisted of a pressure chamber, an elastic silicone pad representing the peritoneal sac, and a silicone mat with bovine muscle tissue representing the abdominal wall. Intrinsic pressure (up to 200 mm Hg) was generated within the pressure chamber by continuous inflation with CO(2). A slit-like or flap-like defect was created in the silicone mat to simulate small or large hernia defects, respectively. The implanted mesh was arranged in both onlay and sublay configurations. A large pore polypropylene mesh with significant anisotropic stretchability was investigated, whereas overlaps of 2, 3, and 4 cm were applied. RESULTS: Despite the application of pressures up to 200 mm Hg, no mesh ruptures occurred. In the slit-like defect model, the minimal overlap required to prevent dislocation at 200 mm Hg was 3 cm using the sublay technique provided that the mesh was positioned with its most stretchable axis parallel to the largest slit dehiscence. Perpendicular rotation of the mesh resulted in dislocation at 160 mm Hg, despite using an overlap of 3 cm. Mesh reinforcement showed less stability in both the onlay position and the flap-like defect. CONCLUSION: An overlap of 3 cm is sufficient to prevent early mesh dislocation. Meshes with anisotropic stretchability should be orientated with the most stretchable axis in the direction of least overlap. PMID- 17723889 TI - Management in patients with liver cirrhosis and an umbilical hernia. AB - BACKGROUND: Optimal management in patients with umbilical hernias and liver cirrhosis with ascites is still under debate. The objective of this study was to compare the outcome in our series of operative versus conservative treatment of these patients. METHODS: In the period between 1990 and 2004, 34 patients with an umbilical hernia combined with liver cirrhosis and ascites were identified from our hospital database. In 17 patients, treatment consisted of elective hernia repair, and 13 were managed conservatively. Four patients underwent hernia repair during liver transplantation. RESULTS: Elective hernia repair was successful without complications and recurrence in 12 out of 17 patients. Complications occurred in 3 of these 17 patients, consisting of wound-related problems and recurrence in 4 out 17. Success rate of the initial conservative management was only 23%; hospital admittance for incarcerations occurred in 10 of 13 patients, of which 6 required hernia repair in an emergency setting. Two patients of the initially conservative managed group died from complications of the umbilical hernia. In the 4 patients that underwent hernia correction during liver transplantation, no complications occurred and 1 patient had a recurrence. CONCLUSIONS: Conservative management of umbilical hernias in patients with liver cirrhosis and ascites leads to a high rate of incarcerations with subsequent hernia repair in an emergency setting, whereas elective repair can be performed with less morbidity and is therefore advocated. PMID- 17723890 TI - Functional evaluation of the grafted wall with porcine-derived small intestinal submucosa (SIS) to a stomach defect in rats. AB - BACKGROUND: Small intestinal submucosa (SIS) represents a novel bio-scaffolding material that may be used to repair hollow-organ defects. However, it is unclear whether neurophysiologic responses return to SIS-grafted areas in the gut. We evaluated the functional recovery of a stomach defect grafted with the porcine derived SIS. METHODS: Twelve rats had a full-thickness defect created in the stomach. SIS was secured to the gastric wall. After 6 months, muscle strips were harvested from within the grafted area to perform both a histologic and a functional study. Additional full-thickness muscle strips were harvested from the posterior in the same stomach as controls. A dose response curve was obtained with carbachol (CCH) or sodium nitroprusside (SNP). Activation of intrinsic nerves was achieved by electrical field stimulation (EFS). RESULTS: The response to CCH and amplitude in EFS showed tonic contraction in both controls and SIS strips in a concentration-dependent and frequency-dependent manner. The magnitude after each stimulation was significantly lower in SIS strips compared with controls (P < .01). However, the contraction ratio of EFS to ED(50) of CCH was not significantly different between the groups. Additionally, SNP produced relaxation in both strips in a concentration-dependent manner. Histologic findings revealed that an insufficient amount of smooth-muscle cells existed in the muscularis propria, whereas compensated growth was observed in the submucosa with nerve regeneration. CONCLUSIONS: This study demonstrates that SIS provides a template for nerve migration to the graft in the rodent stomach. Innervations showed a similar distribution to that observed in the controls. The clinical implications of such findings warrant additional investigation. PMID- 17723891 TI - Thermal sensitization through ROS modulation: a strategy to improve the efficacy of hyperthermic intraperitoneal chemotherapy. AB - BACKGROUND: The purpose of this study was to investigate whether modulation of cellular reactive oxygen species (ROS) provides a synergistic effect with hyperthermia to induce tumor cell death in a colon cancer cell line. MATERIALS AND METHODS: HT-29 colon cancer cells were exposed to heat (43 degrees C) in the presence of the ROS-generating drug, 2-2'-azobis-(2-amidinopropane) dihydrochloride (AAPH) for 1 h. Viable cell mass and apoptosis was measured by MTT and annexin V staining, respectively. Oxidative stress was evaluated by DCFH fluorescence. Protein levels were determined by Western blot analysis. RESULTS: A synergistic effect on cell viability with AAPH was noted under hyperthermic conditions as compared with hyperthermia alone (P < .05). The number of nonviable cells after hyperthermia and AAPH exposure was also significantly increased compared with AAPH at 37 degrees C (42% vs 20%, P < .05). ROS levels were increased modestly with AAPH at 37 degrees C, whereas they increased significantly in a dose-dependent manner with AAPH at 43 degrees C. Transient increases of phosphorylated-p38 and ERK and decreases in phosphorylated-AKT were observed in the cells exposed to AAPH at 43 degrees C. Pretreatment of inhibitors of p38 yielded additional decreases in cell mass when used in combination with AAPH and hyperthermia (P < .05). Increased expression of HSP 27 observed at 43 degrees C was abrogated with AAPH exposure. CONCLUSIONS: Oxidative stress increased the cytotoxic effects of hyperthermia in colon cancer cells. Thermal sensitization through modulation of cellular ROS may represent a novel approach to increase the efficacy of hyperthermia as an anticancer modality. PMID- 17723892 TI - Carotid-subclavian arterial reconstruction: concomitant ipsilateral carotid endarterectomy increases risk of perioperative stroke. AB - BACKGROUND: Carotid-subclavian bypass (CSB) and carotid-subclavian transposition (CST) have excellent long-term patency with low perioperative mortality and morbidity. Carotid endarterectomy (CEA) is necessary for severe ipsilateral internal carotid artery stenosis in a small subset of these patients. CEA can be performed as a combined or separate procedure. This study was undertaken to delineate the results of CSB and CST at our institution and to determine if concomitant CEA with CSB or CST is safe. METHODS: We evaluated the outcome of 36 patients with symptomatic subclavian artery stenosis treated surgically at a single institution during a 22-year period. Outcomes of patients undergoing CSB or CST with concomitant CEA were compared with those of patients undergoing CSB or CST alone. Available literature was reviewed to compare the rate of perioperative stroke following CSB or CST with concomitant CEA versus CSB or CST alone. RESULTS: Twenty-one patients underwent CST and 15 patients underwent CSB. There were 2 (5.6%) deaths and 2 (5.6%) strokes within 30 days of surgery. Concomitant CEA was performed in 6 CST patients and 2 CSB patients. Both perioperative strokes occurred in patients who had concomitant CEA. There were no strokes in the CST or CSB alone group (P = .044). In a collected review of 12 evaluable studies plus our experience, the rate of perioperative stroke was 0.32% in 617 patients who underwent CSB or CST alone versus 4.73% in 148 patients who had concomitant CEA with CSB or CST (P < .001). CONCLUSIONS: Both CSB and CST are safe and effective for symptomatic subclavian artery stenosis, with excellent long-term results. In patients also requiring CEA, the rate of perioperative stroke is significantly higher with a combined procedure. Consideration should be given to performing CEA separately from CSB or CST. PMID- 17723894 TI - Laparoscopic central pancreatectomy: single institution experience of 6 patients. AB - BACKGROUND: Medial pancreatectomy is an alternative technique for benign or low grade malignant tumors of the neck of the pancreas. We describe our experience of laparoscopic central pancreatectomy. METHODS: We conducted a prospective evaluation of laparoscopic pancreatic resection in the Department of Abdominal Surgery at Haut-Leveque Hospital, CHU Bordeaux. From January 1999 until February 2006, 397 patients underwent pancreatic resection for pancreatic lesions, of whom 60 (15%) were enrolled for laparoscopic pancreatic resection. Of the 60 patients, 6 underwent laparoscopic central pancreatectomy. Surgical procedure, postoperative course, and follow-up data were collected. RESULTS: Laparoscopic central pancreatectomy was successful in all patients. In 1 case, we had to perform a laparotomy to find the specimen, which had been lost in the cavity during the anastomosis. The median operative time was 225 minutes (range, 180 to 365 minutes). None of the patients required blood transfusion in the perioperative period, and there was no mortality. Symptomatic pancreatic fistula occurred in 2 patients (33%). None of the patients required reoperation or radiologic drainage. Oral feeding was resumed in a median of 11 days (range, 9 to 21 days). The median postoperative hospital stay was 18 days (range, 15 to 25 days). At a median follow-up of 15 months (range, 4 to 34 months), all patients were alive without exocrine or endocrine insufficiency. CONCLUSIONS: Laparoscopic central pancreatectomy is feasible and safe. Laparoscopic central pancreatectomy may become the standard approach for resection of benign or low-grade malignant tumors of the neck of the pancreas if performed by highly skilled surgeons. PMID- 17723893 TI - A "defined baseline" in PTH monitoring increases surgical success in patients with multiple gland disease. AB - BACKGROUND: Parathyroid hormone (PTH) monitoring with a quick intact PTH (QIPTH) assay is used in minimally invasive exploration for primary hyperparathyroidism (PHPT) in order not to miss multiple gland disease (MGD). Controversy exists on which criterion is most reliable to predict cure. METHODS: QIPTH values of 310 consecutive patients (single gland disease [SGD]: n = 289; MGD: n = 21) with sporadic PHPT were analyzed using 3 different criteria: "Vienna Criterion": >/=50% decay from a defined "baseline" level (right after induction of anesthesia before skin incision) 10 min after excision. "Miami Criterion": >/=50% decay from highest (preincision or preexcision) value 10 min after excision; "Halle Criterion": decay of the PTH- level to less than or equal to 35 pg/mL within 15 min after excision. RESULTS: The "Vienna" and "Halle Criteria" correctly detected MGD in 19 (91%) and the "Miami Criterion" in 12 (57%) of 21 patients. Incorrect prediction of incomplete excision occurred in 22 patients (8%) with SGD, using the "Vienna Criterion" ("Miami Criterion": 2%, "Halle Criterion": 29%). All of these were recognized intraoperatively from unintended intraoperative manipulation (n = 18), technical failure (n = 2), or borderline increased PTH values (n = 2), and they did not lead to bilateral exploration. Analyzing patients with SGD and MGD, accuracy and specificity were 92% and 89% for the "Vienna Criterion," 93% and 54% applying the "Miami Criterion," and 72% and 89% using the "Halle Criterion." CONCLUSION: Strict definition of a PTH "baseline level" ("Vienna Criterion") improves intraoperative diagnosis of MGD, thus reducing reoperations and increasing long-term cure. PMID- 17723896 TI - Moving the cheese: a commentary on debate over the acute care surgery initiative. PMID- 17723895 TI - Intercostal video-assisted mediastinal surgery through an intercostal window (IVAMS): a simpler approach to perform mediastinal parathyroidectomy. PMID- 17723897 TI - Comparison of data extraction from standardized versus traditional narrative operative reports for database related research and quality control. PMID- 17723898 TI - Focal nodular hyperplasia of the liver in an 8-year-old boy. PMID- 17723899 TI - Regarding "the concept of acute care surgery". PMID- 17723900 TI - Analysis of efficacy and safety of drotrecogin alfa (activated) in surgical patients, using an international integrated database. PMID- 17723901 TI - Modified Billroth I after distal gastrectomy for prevention of remnant gastritis? The feasibility report (Billroth I evolved in year 120). PMID- 17723902 TI - What is in a word: Pancreatoduodenectomy or pancreaticoduodenectomy? PMID- 17723903 TI - Celiac axis compression during the expiratory phase as a cause of hepatic ischemia during pancreaticoduodenectomy. PMID- 17723904 TI - Right paramedian sectoriectomy using the double liver hanging maneuver. PMID- 17723906 TI - Sudden cardiac death: epidemiology, mechanisms, and therapy. AB - Sudden cardiac death is a major public health problem affecting 500,000 patients annually in the United States alone. The major risk factor for sudden cardiac death is the presence of coronary artery disease, usually in the setting of reduced ejection fraction. Globally, the incidence is expected to rise sharply as the prevalence of coronary artery disease and heart failure continue to increase. However, sudden cardiac death is a heterogeneous condition and may be caused by acute ischemia, structural defects, myocardial scar, and/or genetic mutations. Sudden death may occur even in a grossly normal heart. Beta-blockers can reduce the risk of sudden cardiac death, while implantable cardioverter defibrillators are effective at terminating malignant arrhythmias. Ejection fraction remains the major criterion to stratify patients for defibrillator implantation but this strategy alone is insensitive and nonspecific. Novel clinical, electrophysiologic, and genetic markers have been identified that may increase precision in patient selection for primary prevention therapy. This review discusses the epidemiology, mechanisms, etiologies, therapies, treatment guidelines, and future directions in the management of sudden cardiac death. PMID- 17723907 TI - Scaling of the resolving power and sensitivity for planar FAIMS and mobility based discrimination in flow- and field-driven analyzers. AB - Continuing development of the technology and applications of field asymmetric waveform ion mobility spectrometry (FAIMS) calls for better understanding of its limitations and factors that govern them. While key performance metrics such as resolution and ion transmission have been calculated for specific cases employing numerical simulations, the underlying physical trends remained obscure. Here we determine that the resolving power of planar FAIMS scales as the square root of separation time and sensitivity drops exponentially at the rate controlled by absolute ion mobility and several instrument parameters. A strong dependence of ion transmission on mobility severely discriminates against species with higher mobility, presenting particular problems for analyses of complex mixtures. While the time evolution of resolution and sensitivity is virtually identical in existing FAIMS systems using gas flow and proposed devices driven by electric field, the distributions of separation times are not. The inverse correlation between mobility (and thus diffusion speed) and residence time for ions in field driven FAIMS greatly reduces the mobility-based discrimination and provides much more uniform separations. Under typical operating conditions, the spread of elimination rates for commonly analyzed ions is reduced from >5 times in flow driven to 1.6 times in field-driven FAIMS while the difference in resolving power decreases from approximately 60% to approximately 15%. PMID- 17723910 TI - C-reactive protein measurement in the patient with vascular disease. AB - C-reactive protein (CRP) is becoming more frequently measured in patients with vascular disease. Awareness of why CRP levels are measured, knowledge of normal versus elevated levels, ability to obtain accuracy in measurement, and teaching appropriate for patients with vascular disease may enhance the care given by vascular nurses. The purpose of this article is to provide a guide for vascular nurses in understanding the role of the serum marker CRP for patients with vascular disease. PMID- 17723911 TI - Review of an article: Badger S, Soong C, O'Donnell M, Boreman C, McGuigan K. Benefits of a supervised exercise program after lower limb bypass surgery. Vasc Endovascular Surg 2007;41(1):27-32. PMID- 17723909 TI - Sudden increase in skin temperature predicts venous ulcers: a case study. AB - Venous ulcers affect approximately 2.5 million adults with chronic venous disease (CVD). Venous ulcers are a significant health problem with a reoccurrence rate as high as 72%. There is a critical need for a prediction/prevention model of venous ulcers that includes objective methods to assess the skin. Among individuals affected by CVD, skin temperature is elevated in the lower extremities. This case study of a patient with CVD highlights the potential predictive usefulness and feasibility of measuring skin temperature with an infrared dermal thermometer as part of the standard of care for venous ulcer prevention. PMID- 17723912 TI - 5 Million Lives Campaign. PMID- 17723915 TI - Mechanisms of drug-induced liver disease. AB - Drug-induced liver injury depends initially on development of hepatocyte stress and cell death, which can be induced directly by parent drugs or by toxic metabolites. Hepatocyte stress can lead to activation of built-in death programs for apoptosis or necrosis. Subsequently, the innate immune system's participation is recruited. The interplay between proinflammatory and anti-inflammatory components of innate immune system determines the outcome of drug-induced liver injury. Both environmental factors and genetic differences in cellular responses to stress and the innate immune response may account for different susceptibilities between individuals to drug-induced liver injury. PMID- 17723916 TI - Causality assessment of drug-induced hepatotoxicity: promises and pitfalls. AB - Drug-induced liver injury is the leading cause of acute liver failure in the United States, but the ability to ascribe hepatic injury confidently to a specific drug remains a challenging and often difficult pursuit. This article explores the ongoing challenges inherent in what is currently a clinical process of elimination made in the attempt of assigning causality in drug-induced liver injury. In particular, it points out the shortcomings and pitfalls that often limit the applicability of the causality-assessment methodologies currently in use. PMID- 17723917 TI - Drug hepatotoxicity from a regulatory perspective. AB - This article summarizes problems of drug-induced liver injury (DILI), as seen from the perspective of the Food and Drug Administration (FDA). After brief consideration of the scope of FDA activities and processes of new drug development and review for possible approval of products for clinical use and marketing, some of the perceived current problems in detection, confirmation, close observation, differential diagnosis, and follow-up of cases of possible DILI in controlled clinical trials are described. Readers are invited to consider possible solutions to the many problems of DILI, propose ways to support research in the field, and keep abreast of progress by visiting the web site at www.fda.gov/cder/livertox. PMID- 17723918 TI - Acetaminophen hepatotoxicity. AB - Acetaminophen is a commonly used antipyretic and analgesic agent. It is safe when taken at therapeutic doses; however, overdose can lead to serious and even fatal hepatotoxicity. The initial metabolic and biochemical events leading to toxicity have been well described, but the precise mechanism of cell injury and death is unknown. Prompt recognition of overdose, aggressive management, and administration of N-acetylcysteine can minimize hepatotoxicity and prevent liver failure and death. Liver transplantation can be lifesaving for those who develop acute liver failure. PMID- 17723919 TI - Hepatotoxicity due to antibiotics. AB - Antimicrobial drugs are important causative agents in idiosyncratic drug-induced liver injury (DILI). As with idiosyncratic DILI in general, antibiotic-induced liver injury is rare but difficult to diagnose and almost impossible to predict. Diagnosis requires awareness of possible causal agents, vigilance in monitoring symptoms and sometimes biochemical tests, attention to careful history taking and establishing temporal association, and exclusion of competing etiologies. In most instances, patients with antibiotic-associated DILI recover if the offending agent is withdrawn in a timely fashion. PMID- 17723920 TI - Nonsteroidal anti-inflammatory drug-induced hepatotoxicity. AB - Nonsteroidal anti-inflammatory drugs are among the most common drugs associated with drug-induced liver injury, with an estimated incidence of between 3 and 23 per 100,000 patient years. Nimesulide, sulindac, and diclofenac seem to be associated with the highest risk and the only risk factor consistently identified is the concomitant use of other hepatotoxic drugs. Diclofenac-induced liver injury is a paradigm for drug-related hepatotoxicity. Recent studies suggest that genetic factors favoring the formation and accumulation of the reactive acylglucuronide metabolite of diclofenac and an enhanced immune response to the metabolite-protein adducts are associated with increased susceptibility to hepatotoxicity. PMID- 17723921 TI - Herbal hepatotoxicity. AB - There is appropriate concern about the potential risk for hepatotoxicity from herbal products because they are unregulated and therefore not standardized with regard to their contents. This is particularly the case for the crude herbals that are commonly formulated as a mixture, so that their ingredients may be ambiguous and even contain harmful contaminants. Presented here is an overview of the more commonly recognized herbal products that have been reported to be associated with liver injury. Although many of them are clearly implicated, there are some, particularly those identified solely through an occasional case report, for which the relationship is uncertain. PMID- 17723923 TI - Drug-induced liver injury associated with HIV medications. AB - Antiretroviral therapy (ART) for HIV infection frequently has been associated with elevated liver enzyme levels. Determining the cause of elevated liver enzyme levels in patients who have HIV is difficult because ART usually consists of three different drugs, patients may be taking additional hepatotoxic medications and patients who have HIV often suffer from other liver diseases. Several agents, however, are recognized as having noteworthy and specific patterns of toxicity. This article reviews the different HIV drug classes, incidence of elevated liver enzyme values by class and by individual drug, risk factors, specific toxicities, and possible mechanisms of injury. PMID- 17723924 TI - Cancer chemotherapy I: hepatocellular injury. AB - Although hepatotoxicity is a frequent concern with all medications, chemotherapeutic agents are more often implicated in causing liver damage than most other drug classes. In many instances, these reactions are considered dose related because cytotoxic therapy directed at rapidly growing cancer cells may readily impact hepatocytes even though they are dividing more slowly. Because the stakes (remission of cancer) are high, so are the risks that the oncologist and the patient are willing to assume. The dose of many chemotherapeutic agents is limited by the toxic effects on the lungs, bone marrow, kidneys, and gastrointestinal system, including the liver. An awareness of the toxic potential of each chemotherapeutic agent is necessary before initiation of new oncologic treatments. PMID- 17723922 TI - Lipid-lowering agents that cause drug-induced hepatotoxicity. AB - The effort to reduce cardiovascular risk factors, including hyperlipidemia, has led to the increased use of lipid-lowering agents. Hyperlipidemic patients often have underlying fatty liver disease, however, and thus may have elevated and fluctuating liver biochemistries. Therefore, caution should be applied before attributing elevated liver tests to lipid-lowering agents. Data indicate that patients who have chronic liver disease and compensated cirrhosis should not be precluded from receiving statins to treat hyperlipidemia. Several recent studies and expert opinion currently fully endorse statin use in patients who have nonalcoholic fatty liver disease and other chronic liver disease if clinically indicated. PMID- 17723925 TI - Cancer chemotherapy II: atypical hepatic injuries. AB - Although chemotherapy generally is accompanied by regular testing for liver enzyme abnormalities, atypical reactions may occur that escape ordinary detection, because hepatocyte injury is not the primary event. The presence of fatty liver, mitochondrial changes, and even biliary abnormalities can be associated with normal or nearly normal liver enzyme levels. This article discusses unique aspects of liver damage associated with cancer chemotherapy. These unique reactions merit special attention and a special vigilance from clinicians. PMID- 17723926 TI - Better understanding of keratoconus and staying up-to-date. PMID- 17723927 TI - Time to go back to school! Is it a good thing? PMID- 17723928 TI - Mechanisms of opioid-induced tolerance and hyperalgesia. AB - Opioid tolerance and opioid-induced hyperalgesia are conditions that negatively affect pain management. Tolerance is defined as a state of adaptation in which exposure to a drug induces changes that result in a decrease of the drug's effects over time. Opioid-induced hyperalgesia occurs when prolonged administration of opioids results in a paradoxic increase in atypical pain that appears to be unrelated to the original nociceptive stimulus. Complex intracellular neural mechanisms, including opioid receptor desensitization and down-regulation, are believed to be major mechanisms underlying opioid tolerance. Pain facilitatory mechanisms in the central nervous system are known to contribute to opioid-induced hyperalgesia. Recent research indicates that there may be overlap in the two conditions. This article reviews known and hypothesized pathophysiologic mechanisms surrounding these phenomena and the clinical implications for pain management nurses. PMID- 17723929 TI - Patient satisfaction with postoperative pain management--effect of preoperative factors. AB - Patients often suffer from inadequate treatment of postoperative pain. The purpose of this study was to survey the factors affecting patient satisfaction with postoperative pain management. A questionnaire with 41 items was given on the third postoperative day to 102 patients undergoing major orthopedic or vascular surgery. Intensity of pain was assessed using a 10-cm visual analogue scale (VAS) and given analgesics were recorded. Nurses (n = 74) working on the wards received a questionnaire concerning attitudes toward management of pain. The questionnaires were returned by 75.5% of the patients and 86.3 % of the nurses. Mean VAS on all wards was 2 (scale 0-10). Twenty-eight percent of the patients agreed having hard pain during the day of the operation and 39.3% during the first postoperative night. Eighty percent of the patients were satisfied with pain management, and their satisfaction correlated significantly with received preoperative information (p < .01) and preoperative well-being (p < .01). There is discrepancy between the amount of experienced pain and values of the frequent VAS recordings, which does not seem to be due to the nurses' attitudes toward pain. Preoperative interview is important tool to receive and give information concerning postoperative pain management. PMID- 17723930 TI - Nurse case management program of chronic pain patients treated with methadone. AB - Methadone treatment in chronic pain patients is still limited owing to misconceptions about addiction, safety, and its unique pharmacokinetic and pharmacodynamic properties. Nevertheless, patients with chronic noncancer pain are frequently treated with methadone at our Pain Centre either as the first opioid of choice, for specific pain conditions, or as a second-line opioid in patients developing tolerance or intractable side effects with other opioids. The aim of this study was to examine whether a nurse case management program of chronic pain patients treated with methadone is feasible and safe in trying to improve patients' care in an ambulatory setting. This program consisted of three phases: initial primary education session, telephone follow-up during methadone titration, and a subsequent maintenance period. The nurse case manager functioned autonomously and when required reported to and consulted the physician. The study included 75 subjects and was done over a nine-month period by completing follow up questionnaires for every call. Of a total of 194 recorded calls, 41% were unscheduled. Forty-four percent of phone calls resulted in a methadone increase and 11% led to a decrease or cessation of methadone. No patients developed serious morbidity or mortality. Fifty-seven percent of patients were either satisfied or very satisfied with their treatment. A nurse-led case management program of methadone in chronic pain patients can improve patient care in an ambulatory setting. PMID- 17723934 TI - Symptomatic relief: left ventricular assist devices versus resynchronization therapy. AB - In patients who have end-stage heart failure, medical therapy is of limited use, and heart transplantation is frequently not an option because of the shortage of donor hearts. Two new treatment options, left ventricular assist devices (LVADs) and implantable cardiac resynchronization therapy (CRT) devices, can improve survival and quality of life in patients who have heart failure. Both types of devices are easy to implant. However, LVADs carry the risk of infection and mechanical failure, and CRT is ineffective in a substantial proportion of patients who have heart failure. Therefore, methods must be devised to identify patients who have heart failure who are likely to benefit from these devices. Data suggest that early LVAD implantation, before end-stage heart failure develops, is critical to slowing or reversing disease progression. Similarly, in indicated patients who have less advanced disease, CRT may be particularly beneficial. PMID- 17723935 TI - Should patients who have persistent severe symptoms receive a left ventricular assist device or cardiac resynchronization therapy as the next step? AB - Currently, cardiac resynchronization therapy (CRT) should be considered before a left ventricular assist device for most patients who have moderate or severe left ventricular systolic dysfunction and have not responded symptomatically to conventional pharmacologic measures. There is little evidence that the severity of cardiac dyssynchrony as measured using current techniques is useful in predicting the benefits of CRT. QRS duration on the surface ECG is a surrogate marker of the severity of the left ventricular ejection fraction as well as of several types of dyssynchrony. More clinical trials are required to determine whether excluding patients who have QRS duration less than 120 msec or those who have no evidence of dyssynchrony from implantation of CRT is appropriate. Perhaps all patients who have moderate or severe left ventricular systolic dysfunction should be considered for CRT, either to improve symptoms if they are persistent or relapsing, or to improve outcome. In the longer-term future, it is possible that the development of less expensive, small, and safe left ventricular assist devices will supplant the role of both CRT and CRT-defibrillator devices. PMID- 17723936 TI - Does myectomy convey survival benefit in hypertrophic cardiomyopathy? AB - Obstructive hypertrophic cardiomyopathy (HCM) can be treated by transaortic subaortic myectomy, which has been shown to improve patients' symptoms and abolish left ventricular outflow tract obstruction. Different options, such as dual chamber pacing and septal ethanol ablation, are now available for the management of obstructive HCM, and it is important to evaluate the risks and benefits of myectomy, especially its impact on survival. In this article, the authors review the clinical course of obstructive HCM and the early and long-term results of surgery. They examine the outcomes of obstructive HCM in patients after surgical versus conservative therapy. In addition, they review the studies that have compared other techniques to surgery for the management of obstructive HCM. PMID- 17723937 TI - Valve pathology in heart failure: which valves can be fixed? AB - Heart transplantation has evolved to become the gold standard treatment for patients who have symptoms of severe congestive heart failure associated with end stage heart disease. From an epidemiologic perspective, this treatment is "trivial" because less than 2800 patients in the United States are offered transplantation because of limitations of age, comorbid conditions, and donor availability. New surgical strategies to manage patients who have severe end stage heart disease have therefore evolved to cope with the donor shortage in heart transplantation and have included high-risk coronary artery revascularization, cardiomyoplasty, and high-risk valvular repair or replacement. PMID- 17723938 TI - Patients who have dilated cardiomyopathy must have a trial of bridge to recovery (pro). AB - This article documents the experience that mechanical unloading of a diseased heart by application of a left ventricular assist device showing the consequence of functional improvement and weaning thereafter is a realistic option. The patient who has been weaned first is still doing fine with sufficient and stable cardiac function more than 10 years after device removal. Furthermore, it is discussed how to identify potential patients for weaning, what problems may arise, how the follow-up should be designed, the medication before and after weaning, the surgical procedure, and the general management. Moreover, the authors outline the difficulties that result from the gene and protein expression analysis of the diseased myocardium when compared to the cardiac function. PMID- 17723939 TI - Patients who have dilated cardiomyopathy must have a trial of bridge to recovery: the case against that proposition. AB - The idea that patients who have dilated cardiomyopathy (presumably a large heart with near-normal coronary arteries) must have a trial of bridge to recovery is risible. Many such patients should be managed so that they go directly to transplantation and others may be better treated with drug therapy. Some may be more suited to destination therapy. What is needed in this field is more precise terminology, clearer statements of clinical intent at the time of device insertion, improved characterization of patients, more accurate clinical assessment, and above all more information from randomized clinical trials. PMID- 17723940 TI - Cardiac transplantation: any role left? AB - The authors analyze the question of whether heart transplantation still has a role in the current era of complex technologies. To achieve this objective, the authors first discuss the known benefits of different therapeutic modalities currently available for patients who have end-stage heart failure, including pharmacologic management, electrophysiologic therapies, high-risk surgical strategies, implantation of mechanical circulatory support device therapy, and heart transplantation. The authors then evaluate the current developments and future perspectives in the field that may influence the likelihood of heart transplantation to remain the therapeutic modality of choice for end-stage heart failure. PMID- 17723941 TI - Destination therapy: does progress depend on left ventricular assist device development? AB - The role of therapy using mechanical circulatory support devices has evolved rapidly over the last two decades. New developments in the field achieved smaller adverse events, but, currently, only minor improvements in survival were observed in published observational data. The authors discuss the development of mechanical circulatory support devices as a "destination therapy" option for patients who have end-stage heart failure and are ineligible for heart transplantation as it relates to left ventricular assist device development. PMID- 17723942 TI - Lifetime circulatory support must not be restricted to transplant centers. AB - Heart failure that does not respond to maximum medical management is a frightening and debilitating condition. The patients have poor quality of life and become progressively more dependent on hospital admissions for escalating medical therapy. Long-term circulatory support can provide symptomatic relief and improved survival for those who do not have access to cardiac transplantation. User-friendly blood pumps with proven durability already exist. Rotary blood pumps must be made available in centers other than those involved in transplantation. The mystique must be removed from this relatively simple intervention. PMID- 17723943 TI - Factors predictive of elevated serum CA125 levels in patients with epithelial ovarian cancer. AB - Our objective was to identify factors that correlate with high CA125 (cancer antigen 125) concentrations in Tunisian women with epithelial ovarian cancer and to introduce recommendations for reporting and interpreting individual CA125 assay results. We analyzed repeated serum CA125 levels, by the immunoenzymatic assay using an AxSym CA125 kit, in 90 patients who were treated for ovarian cancer from 1994 to 2006 in CHU Farhat Hached Sousse Tunisia. Using a logistic model, we found that carcinosis is significantly predictive of high levels of serum CA125 (p = 0.005). A woman's age (> or = 45 years, p = 0.016) and menopausal status (postmenopausal patient, p = 0.034) are also predictive of increased CA125 concentration. Patients with serous histological subtype have higher CA125 values (p = 0.001). Presence of ascites is associated with high serum CA125 values and thus could be considered as a predictor of high serum CA125 concentration (p = 0.023). The International Federation of Gynecology and Obstetrics stage and primary tumor size are not significant predictors of CA125 concentrations (p > 0.05). We conclude that clinically significant parameters should lead to the best interpretation of rising CA125 levels and consequently to more appropriate management of epithelial ovarian cancer patients. PMID- 17723945 TI - [Use of body weight and body surface area in dosing of anticancer agents in adult patients]. AB - Dosing of anticancer drugs in adults is mostly adjusted to estimated body surface area or body weight. Dose normalisation to body size is assumed to decrease the interindividual pharmacokinetic and pharmacodynamic variability. This approach is rarely validated before approval. Theoritically, body size should be used only if it has been demonstrated that it constitues a significant factor affecting clinical variability. Recent studies have shown, a posteriori, that several marketed anticancer agents could be administered at a fixed dose. Moreover, the abandon of body surface area in dosing of new drugs in phase I trials has been recommended. At the present time, body size continues to be used in the dosing of new agents in adult patients. This review presents the concepts and the limits of weight and body surface area-based dosing of anticancer drugs in adult patients. PMID- 17723944 TI - [Fertility preservation in adolescent cancer patients]. AB - Recent advances in cancer therapy have improved the survival rate of infant and adolescent facing cancers. The objective of treatment is not only to cure cancer but also to limit its secondary consequences. Impaired fertility is an important sequel of numerous treatments against cancer. Therefore, efforts to maintain fertility must be a major consideration in the treatment plan. This review focuses on various options for preserving fertility in adolescents. In female patients, ovarian transposition out of the radiation field may considerably reduce the radiation received by the ovaries. The benefits of GnRH analogue are not yet clear and apoptosis inhibiting agents are unavailable. Embryo freezing is the most reliable method to preserve fertility. This method is time-intensive, requires a partner, and ovarian stimulation may not always be compatible with the need of starting treatment against cancer immediately. Oocyte cryopreservation is an experimental technique that can be used in post-pubertal patients irrespective of their marital status. The cryopreservation of mature oocytes has similar constrains as embryo freezing ; in addition the technique is not as well established and the pregnancy rates obtained are much lower than those achieved with embryos. Freezing of immature oocytes followed by in vitro maturation in spite of its theoretical advantages is inefficient in current practice. Ovarian tissue cryopreservation offers great hope because it has the potential to preserve a large number of primordial follicles without any ovarian stimulation and preliminary trials have shown some success. For male adolescents cancer patients semen cryopreservation is a successful alternative that should be offered systematically when cancer therapies that may impair gonadal function are indicated. For prepubertal males there is presently no standardized technique for preserving fertility ; however, the development of testicular germ-cell harvest needs to be considered. PMID- 17723946 TI - [Lung cancer treatment in elderly patients]. AB - The treatment of an elderly patient with a bronchial carcinoma is a daily challenge for the physician, because of the high incidence of lung carcinoma and a population getting older. The treatment has to be adapted, after geriatric assessment and evaluation of comorbidities, iatrogenic complications being more frequent and more severe in these patients. At the opposite, these patients are to often under-treated. This article will update the therapeutic strategy for non small cell and small-cell lung carcinoma in the elderly. PMID- 17723947 TI - [Interests and perspectives of PET-CT for breast cancer: review of the literature]. AB - 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a technique of functional imaging whose interest in oncology does not cease growing. This article summarizes the results of the technique in senology. For the initial evaluation of locally advanced breast cancer (extended primitive lesion, axillary lymph nodes...), the FDG-PET makes it possible to evaluate lymph nodes (in particular internal mammary nodes) and to seek remote metastases. The sensitivity of the examination appears nevertheless low for the secondary lesions of small size and for bone metastases of osteoblastic form, for which the performances of the bisphosphonates scintigraphy are higher. For the search of a loco-regional or remote recurrence, the performances of FDG-PET are very interesting, including in the event of normality of the biological assessment. The impact of FDG-PET on the therapeutic strategy is undeniable and seems estimated at least 20%. FDG-PET is not recommended for the characterization of a breast lesion. In addition to the small tumoral size, the causes of false negative are mostly represented by the lobular histological form, by the tumours with low proliferation, the tumours of low grade and the well differentiated lesions. The causes of false positive are mainly in relation with inflammatory and/or infectious phenomena. For similar reasons, FDG-PET cannot replace the anatomy-pathological analysis of the axillary nodes. To evaluate the effectiveness of a neo-adjuvant chemotherapy, FDG-PET seems to be a powerful examination. Nevertheless, the data of the literature appear insufficient to recommend it in current practice. It is the same way for the prognostic interest. PMID- 17723948 TI - [Management of lymphedema of the upper extremity after treatment of breast cancer]. AB - Management of breast cancer-related lymphedema is based on complex decongestive physiotherapy including two phases. The first intensive phase reduces lymphedema volume with daily low stretch bandages associated with manual lymph drainage. Treatment includes exercises and skin care. The second phase of treatment consists of stabilization of lymphedema volume with regular overnight self bandaging, daily elastic compression garment and manual lymph drainage if needed. Lymphedema volume may be stabilized after the intensive phase if the patient is compliant to long term treatment. Practical advices such as weight control and skin care to avoid cellulitis should be given. Regular and prolonged medical follow-up is required for this chronic disease to maintain motivation of the patient. PMID- 17723949 TI - [Hysteroscopic injection in sentinel node biopsy for endometrial cancer increases the frequency of para-aortic drainage: Is it necessary to reconsider the role of para-aortic lymphadenectomy?]. AB - In cancer research, regional lymph node status is a major prognostic factor and a decision criterion for adjuvant therapy. The sentinel node procedure, which has emerged to reduce morbidity of extensive lymphadenectomy, remains a major step in the surgical management of various cancers. In endometrial cancer, the sentinel node biopsy is still at the stage of feasibility. The main problem of the diffusion of the sentinel node biopsy in endometrial cancer is the absence of injection site consensus. The different injection sites (myometrial, pericervical and hysteroscopy) allow to identify para-aortic lymph node drainage. In this article, we review the interest of hysteroscopic injection in endometrial cancer. This injection site could contribute to select the patients potentially being able to profit from a lombo-aortic lymphadenectomy. PMID- 17723950 TI - [Propensity score: interest and limits]. AB - Propensity score, an indicator of the propensity to get one treatment among two (or more), is encountered in non randomized studies (prospective or retrospective). It is calculated after the research of predictive factors for treatment attribution, and corresponds to the probability to receive one of the treatments conditional to variables observed before treatment. This probability is usually generated thanks to a logistic regression equation. This score sums up by itself a whole set of parameters. It can be used as cofactor in other multivariate models that aim to evaluate with a reduced risk of confusion, the impact of therapeutical modalities on such end-points as survival, morbidity, secondary effects or quality of life. It appears very convenient to realize matching or stratification in order to compare these end-points among resulting subgroups. Despite this advantage that enables to obtain a posteriori similar subgroups, this method cannot pretend to reach the level of evidence of randomized trials, because absence of bias is never guaranteed. Apart from this major methodological weakness, propensity score appears less useful in studies provided with a large population, since in such cases, multivariate models can include enough covariates to produce in a secure way stable conclusions. When samples are small, this score remains interesting although its reliability, once more, depends on sample size and conclusions need nuances. Examples are included to illustrate the topic. PMID- 17723951 TI - [Cutaneous melanoma and sentinel lymph node biopsy: where are we today?]. AB - Malignant cutaneous melanoma is the cancer which has the most increased these last ten years. His prognose is linked with melanoma thickness, tumoral ulceration and lymph node metastasis. The research of these node metastasis is important for the prognosis and the treatment. The sentinel lymph node biopsy is used since 1991 and is now considered as a reliable choice for the patient staging. However, his therapeutic interest remains discussed. We discussed the used of the sentinel lymph node biopsy for malignant cutaneous melanoma with the last publications. PMID- 17723952 TI - [What's new in sentinel node biopsy?]. AB - Sentinel node (SN) biopsy is become a standard of care in breast cancer surgical practice. However, the advent of this technique, recently discussed during the 29th San Antonio Breast Cancer Symposium 2006, revealed new questions, which the concept of the SN procedure raises: can we increase the current indications? Could be axillary lymph node dissection avoided in patients with metastatic SN? the morbidity of the biopsy of the SN, which is the prognostic value of micrometastatis discovered by the diffusion of the ultra-stadification of the SNs? PMID- 17723953 TI - [Positive sentinel node biopsy in breast cancer: is axillary surgery necessary in all cases?]. AB - Our retrospective study analyzes various factors to evaluate the risk of invasion of the not sentinel node when the sentinel node biopsy is positive in the infiltrated breast cancers. We compared in single varied then multivaried analysis, various parameters between two groups: positive not sentinel nodes and negative not sentinel nodes among 180 cases of positive sentinel node biopsy between 2001 and 2004. At the time of the single varied analysis, seem to be risk factors of non sentinel node involvement: the histopronostic SBRIII rank, positive a HER2neu status, the presence of extracapsulal node extension and infiltration of the sentinel node by a macrometastasis. The tumoral embol, the absence of hormonal receivers, a tumoral size > 10 mm and the number of sentinel node taken appear at the limit of the significativity. In multivaried analysis, SBRIII rank and the presence of an extracapsular node extension remain related to non sentinel node involvement. The histological type, association with a CIS, the size of the sentinel nodes, the number of positive sentinel nodes and the year of surgery are nonsignificant. Additional axillairy clearing out at the time of a positive node sentinel biopsy should be discussed according to different criteria determined by a precise histological analysis. PMID- 17723954 TI - [Family mesotheliomas: genetic interaction with environmental carcinogenic exposure?]. AB - Our patient was refered to hospital for a malignant mesthelioma 22 years after the prior diagnosis of a mesothelioma in his brother. Their family history included others cancers. No exposure to asbestos was documented in brother's history. Literature is rich with family mesothelioma reports. Most of them are linked to an occupationnal asbestos exposure. But, some studies suggest that family genetic factors are involved in the development of mesothelioma: (genetically transmitted mesotheliomas in Turkish families in Cappadoce, family clustering of cancers including mesotheliomas, inhibition of tumor suppressor genes (INK4A, p53, Nf2...), a small proportion of mesothelioma among asbestosis exposed workers. Many studies suggest an interaction between genetic and environment. A genetic predisposition could lead to an increased susceptibility to carcinogenic factors. PMID- 17723955 TI - [Cost/effectiveness analysis of adjuvant therapy with trastuzumab in patients with HER2 positive early breast cancer]. AB - Trastuzumab (Herceptin), a recombinant, humanised, monoclonal-antibody that targets human epidermal growth factor receptor 2 (HER2), has been approved as an adjuvant therapy for HER2-positive early breast cancer. The aim of this study was to assess the incremental cost-effectiveness ratio of this treatment compared with adjuvant therapy alone in the French setting. A cost-effectiveness analysis was performed using a Markov state transition model. The transition probabilities were estimated from the interim results of the Hera trial. Unit costs data were mainly estimated in a French Oncology Center (Georges-Francois Leclerc, Dijon). The model estimated that overall mean survival of patients treated with trastuzumab was 20.08 years versus 16.23 in the observation group (3.85 life years gained). For 1 000 patients with a 10-year follow-up, an adjuvant therapy with trastuzumab would avoid 49.7 loco-regional recurrences, 179.5 distant recurrences and 133.4 deaths. The incremental discounted cost of trastuzumab therapy over a lifetime horizon was estimated at 27594 euro per patient in association with a discounted gain of 2.27 life-years. In accordance with the techniques of economical evaluation, the utilization of trastuzumab as an adjuvant therapy in patients with early HER2 positive breast cancer improves patient survival with an acceptable cost-effectiveness ratio in the French setting (incremental cost-effectiveness ratio of 12,148 euros /LYG). PMID- 17723956 TI - [Risk of second cancer after germinal cell testicular cancer: study from the data of Doubs cancer registry]. AB - Testicular cancer, both seminoma and nonseminoma tumours, account for 1 to 1.5 % of male cancers. Many studies have shown that the risk of a second cancer after radiotherapy is dependent on the size of the exposure fields and the strength of delivered doses of radiotherapy. According to the literature, the relative risk of second cancer among patients treated by irradiation for seminoma limited to the testis varies from 1.5 to 1.9. We conducted a retrospective epidemiological study to measure the risk of second cancer in a population treated for both seminoma and nonseminoma tumours. The study period included patients who were diagnosed from 1978 to 2002. Data were provided by the Doubs cancer registry. Among these 291 cases of testicular cancer, we found 11 cases of second cancer after 157 seminomas (stomach, lungs, testis, ORL, kidney and oesophagus), and 3 cases after 134 nonseminomas (thyroid, kidney and testis). We found a high risk for second pulmonary and testicular cancers (standardised incidence ratio almost statistically significant). While our results are not conclusive regarding the etiology of these second cancers, they do form a useful, comparative basis for further study. They constitute the first step of a study that will be carried out on the risk related to radiation after orchidectomy. PMID- 17723957 TI - [Can children visit their relatives in an adult ICU?]. AB - For the last three years, our oncology ICU (intensive care unit) has been opened to visiting children between 0 and 18 years. Our objective was to attempt to decrease the psychological burden in critically ill cancer patients and their children. We report here the evaluation of this new policy. Encouraged by the child psychologists in our hospital, we first recorded the opinions of the nursing staff, patients and relatives about this innovative approach. As our preliminary findings were favourable, a liberalised greeting and education policy for visiting children was implemented. A dedicated procedure was followed in order to provide children with a better understanding of their parent's disease, to alleviate any traumatic experience the visit might cause and to create an environment where mutual confidence would reign. After 2 years, each visiting child, patient, accompanying parent and the nursing staff were directly questioned using a specifically designed questionnaire. The daily lives of the staff, children, families and patients themselves appeared to be dramatically improved, even in the most difficult medical situations. Based on these promising results, the new policy has definitively been adopted in our unit. We propose that children ought to be allowed to visit a parent in the ICU and that this policy warrants evaluation in other types of units. PMID- 17723958 TI - [Towards a culture of prevention? A definition problem and conceptual distinction]]. PMID- 17723959 TI - Living with cancer: the journey from victim to survivor. PMID- 17723960 TI - Port navigation: let the journey begin. AB - Central venous access plays an important role in modern medical patient assessment and treatment. The use of central venous access devices has become routine in the oncology setting. Clinical oncology nurses need to know how the devices function, how to provide proper care, and how to manage potential side effects. The focus of this article will be on the navigation of implanted, skin tunneled ports. PMID- 17723961 TI - Inpatient diabetes mellitus in the oncology setting. AB - CASE STUDY: A.B. is a 32-year-old Caucasian man with a significant, 12-year medical history of diabetes mellitus type I as well as a history of hypertension and hypercholesterolemia. He presented to his primary care doctor with blurred vision and was referred to a retinal specialist, who diagnosed hemorhagic and leukemic retinopathy resulting in limited vision. A complete blood count was drawn during the visit with his retinal specialist. The results were abnormal, revealing a white blood cell count of 30,000/mm3, platelet count of 70,000/mm3, and a hemoglobin of 12.2 gm/dl. The peripheral smear showed peripheral blasts. A.B. was referred to a hematologist, who performed a bone marrow aspiration, confirming the diagnosis of pre-B-cell acute lymphocytic leukemia (ALL). Cytogenetic studies revealed positivity for the Philadelphia chromosome and a translocation of genes 4 and 11. PMID- 17723962 TI - Evaluating patients with mildly elevated transaminase levels. AB - CASE STUDY: S.B. is a 52-year-old woman with recurrent stage IV ovarian cancer. She initially presented three and a half years ago with complaints of abdominal pain, increased abdominal girth, and abdominal bloating. A CA-125 blood test was elevated, and a computed tomography scan of the abdomen and pelvis revealed bilateral ovarian masses highly suspicious for malignancy. She was taken to surgery for a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and suboptimal tumor reduction. Pathology revealed poorly differentiated papillary serous ovarian cancer. Metastatic disease was noted in the rectosigmoid area and vaginal apex. Postoperatively, she received six cycles of paclitaxel and carboplatin. At completion, her CA-125 normalized and imaging studies showed no evidence of disease. However, within three months, her CA-125 was elevated and a palpable mass at the vaginal apex was proven by biopsy to be recurrent disease. PMID- 17723963 TI - Easy to write? Creating easy-to-read patient education materials. AB - The Leukemia & Lymphoma Society develops and distributes both detailed and easy to-read booklets intended to help patients and caregivers communicate with healthcare providers about their treatment and support needs. The easy-to-read booklets initially were developed for newly diagnosed patients; however, the society has learned that all patients with cancer are likely to benefit from the information at some point in their journeys. To date, the society has developed easy-to-read booklets about acute lymphocytic leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, lymphomas, myeloma, and coping with blood cancer. All booklets are free to patients, healthcare providers, and the general public, and most titles are available in Spanish-language versions. They can be ordered through the society's Information Resource Center (800-955-4572, infocenter@lls.org, or www.lls.org) or its 68 chapters. This article focuses on the development of the booklet Myeloma: A Guide for Patients and Caregivers and includes a handout based on its content. PMID- 17723964 TI - Nursing care of patients receiving high-dose, continuous-infusion interleukin-2 with pulse dose and famotidine. AB - High-dose, continuous-infusion interleukin-2 (IL-2) followed by pulse dose and concurrent administration of famotidine has demonstrated response rates of 64% and 33% in patients with metastatic melanoma and metastatic renal cell carcinoma, respectively. Currently, no information is available concerning the nursing care of patients receiving that IL-2 regimen. Given the high response rates of patients on the treatment, attention by the nursing profession is warranted. Effective nursing care of patients receiving IL-2 is essential to the regimen's success. Recognition and prompt treatment of common side effects lead to better patient outcomes. This article provides nurses with an overview of the treatment regimen, expected side effects, psycho-social considerations, and discharge instructions for patients receiving continuous-infusion plus pulse IL-2 and famotidine. PMID- 17723966 TI - A review of anemia management in the oncology setting: a focus on implementing standing orders. AB - Standing orders serve an important role in various healthcare settings by empowering nurses to implement certain procedures and activities on behalf of physicians, enabling more immediate interventions, and ultimately improving patient care. Standing orders are based on established clinical practice guidelines and are well suited for supportive interventions. Several evidence based clinical practice guidelines are available for the treatment of anemia in patients with cancer. The guidelines can serve as a basis for the development of standing orders for the management of treatment-related anemia in patients with cancer, which will enable the delivery of consistently high-quality care to patients. A major advantage to the implementation of standing orders is that patients with suboptimal hemoglobin levels can be treated by oncology nurses in a timely manner and receive high-quality care that is consistent with available clinical evidence. PMID- 17723965 TI - Pseudomyxoma peritonei syndrome of appendiceal origin: an overview. AB - Pseudomyxoma peritonei (PMP) syndrome is an uncommon, slowly progressive condition that usually arises from perforation of an adenoma in the appendix. PMP syndrome is characterized by mucin accumulation in the peritoneal cavity. Mucinous implants are found on all peritoneal surfaces and the omentum. PMP syndrome rarely metastasizes outside the abdominal cavity but remains a fatal illness as the space in the abdomen and pelvis required for normal function of the gastrointestinal tract becomes filled with copious amounts of the mucinous tumor. Treatment options include observation, aggressive debulking surgery, intraperitoneal chemotherapy, radiotherapy, and mucolytic agents. PMID- 17723967 TI - A model of chemotherapy education for novice oncology nurses that supports a culture of safety. AB - Chemotherapy education at a mid-sized community hospital was redesigned to help novice oncology nurses improve patient safety and their own practice by implementing error prevention techniques during chemotherapy administration. Using a proactive approach with multidisciplinary participation and open communication, a systems analysis was conducted to identify potential chemotherapy errors. Then, chemotherapy processes were devised or strengthened to avoid errors. The project required a philosophical shift from error measurement to safety promotion. PMID- 17723968 TI - Intravesical antineoplastic therapy following transurethral resection of bladder tumors: nursing implications from the operating room to discharge. AB - An aging population and latent effects from exposure to carcinogens will likely augment the current trend of increased incidence of urinary bladder cancer. Intravesical antineoplastic therapy is a common treatment for urinary bladder cancer. Transurethral resection of bladder tumors often is followed immediately by the instillation of an antineoplastic agent in the operating room or postanesthesia care unit. Oncology nurses, who have a unique knowledge of safe handling and patient care, can improve staff safety and patient outcomes in several areas of healthcare organizations, as well as reduce the mortality and morbidity of urinary bladder cancer by learning more about the disease and intravesical antineoplastic therapy. PMID- 17723969 TI - The use of oral transmucosal fentanyl citrate during high-dose-rate gynecologic brachytherapy. AB - Gynecologic brachytherapy is a form of cancer treatment in which radioactive sources are placed into the pelvic organs via specialized applicators. Traditional low-dose-rate (LDR) brachytherapy has been performed over several days in a hospital setting. Since the 1990s, high-dose-rate (HDR) brachytherapy has been used increasingly because of its decreased treatment time, outpatient administration, and equal or superior efficacy compared with LDR treatment. However, the management of procedural pain in the radiation oncology setting has not been studied extensively. The purpose of this article is to discuss the use of oral transmucosal fentanyl citrate (OTFC) for the management of pain during gynecologic HDR brachytherapy. OTFC provides noninvasive, rapid analgesia with a low incidence of side effects and may be appropriate for other forms of procedure related cancer pain. PMID- 17723970 TI - The role of high-dose chemotherapy supported by hematopoietic stem cell transplantation in patients with multiple myeloma: implications for nursing. AB - Multiple myeloma (MM), a neoplastic proliferation of plasma cells originating from the B-cell line, is associated with deleterious complications and poor outcomes. The failure of conventional combination chemotherapies to improve the overall survival of patients with MM has led to the use of high-dose chemotherapy supported by stem cell transplantation (SCT). Although several novel therapies have emerged since the late 1990s, their survival benefits are undetermined. High dose chemotherapy with SCT provides better response rates compared to conventional chemotherapy and yields a trend toward greater survival benefits, especially with the use of a tandem (two successive) transplantation strategy. This article discusses standard SCT in patients with MM and some of the new transplantation strategies, including tandem autologous SCTs and reduced intensity nonmyeloablative allogeneic SCT, and their implications for nursing. PMID- 17723971 TI - Lenalidomide: a new agent for patients with relapsed or refractory multiple myeloma. AB - Lenalidomide is a potent, novel thalidomide analog that has demonstrated promising clinical activity in patients with relapsed or refractory multiple myeloma (MM). It is a lead immunomodulatory drug currently approved by the U.S. Food and Drug Administration. Neutropenia, thrombocytopenia, and thromboembolic events are common adverse effects associated with lenalidomide therapy in patients with MM. Careful monitoring of those known serious adverse effects is essential to prevent life-threatening complications. This article discusses lenalidomide's mechanisms of action, clinical trial results, and the management of common adverse effects in patients with MM. PMID- 17723973 TI - Acupressure for chemotherapy-induced nausea and vomiting: a randomized clinical trial. AB - PURPOSE/OBJECTIVES: To compare differences in the chemotherapy-induced nausea and vomiting (CINV) among three groups of women (acupressure, placebo acupressure, and usual care) undergoing chemo-therapy for breast cancer. DESIGN: A multicenter, longitudinal, randomized clinical trial throughout one cycle of chemotherapy. SETTING: Ten community clinical oncology programs associated with the M.D. Anderson Cancer Center and nine independent sites located throughout the United States. SAMPLE: 160 women who were beginning their second or third cycle of chemotherapy for breast cancer treatment and had moderate nausea intensity scores with their previous cycles. METHODS: Subjects were randomized to one of three groups: acupressure to P6 point (active), acupressure to SI3 point (placebo), or usual care only. Subjects in the acupressure group were taught to apply an acupressure wrist device by research assistants who were unaware of the active acupressure point. All subjects completed a daily log for 21 days containing measures of nausea and vomiting and recording methods (including antiemetics and acupressure) used to control these symptoms. MAIN RESEARCH VARIABLES: Acute and delayed nausea and vomiting. RESULTS: No significant differences existed in the demographic, disease, or treatment variables among the treatment groups. No significant differences were found in acute nausea or emesis by treatment group. With delayed nausea and vomiting, the acupressure group had a statistically significant reduction in the amount of vomiting and the intensity of nausea over time when compared with the placebo and usual-care groups. No significant differences were found between the placebo and usual-care groups in delayed nausea or vomiting. CONCLUSIONS: Acupressure at the P6 point is a value added technique in addition to pharmaceutical management for women undergoing treatment for breast cancer to reduce the amount and intensity of delayed CINV. IMPLICATIONS FOR NURSING: Acupressure is a safe and effective tool for managing delayed CINV and should be offered to women undergoing chemotherapy for breast cancer. PMID- 17723972 TI - A test of the self-help model and use of complementary and alternative medicine among Hispanic women during treatment for breast cancer. AB - PURPOSE/OBJECTIVES: To describe the relationships in Braden's Self-Help Model of side-effect burden to uncertainty, complementary and alternative medicine (CAM), self-care, and quality of life (QOL) in Hispanic women during breast cancer treatment. DESIGN: Descriptive, correlational; convenience sample; cross sectional design. SETTING: An outpatient oncology clinic in a public setting of a metropolitan community in southern Texas. SAMPLE: 137 Hispanic women receiving or completing treatment for breast cancer. METHODS: Participants completed a comprehensive set of instruments. Analyses included a correlation of variables and multiple regressions to examine variables for potential theoretical relationships. MAIN RESEARCH VARIABLES: CAM use, uncertainty, and enabling skills. FINDINGS: CAM use as a resource to reduce uncertainty for Hispanic women during breast cancer treatment was not supported. As a type of self-care, CAM was minimally effective in improving QOL. The greater the side-effect burden that Hispanic women experienced, the more uncertainty and depression and lower QOL scores were found. In contrast, women who were involved in CAM self-care had higher QOL scores. CONCLUSIONS: The study results provide valuable information about understanding CAM's role during breast cancer therapy among Hispanic women. The model-testing findings indicated strong support for a predicted pattern in Braden's Self-Help Model with a slight trend for CAM as a special type of self care. IMPLICATIONS FOR NURSING: The findings further inform the concept development of CAM and model building. Additional research with a longitudinal design is needed to understand how CAM is used throughout the breast cancer treatment trajectory and will contribute to knowledge guiding nurses in facilitating self-care interventions for Hispanic women. PMID- 17723974 TI - Fashionable pink camels. PMID- 17723975 TI - Prevention and early detection of cancer in the United States. PMID- 17723976 TI - Healthcare coverage for the uninsured. PMID- 17723977 TI - Nurses' responsibility to patients requesting assistance in hastening death. PMID- 17723978 TI - Bringing an inpatient palliative care program to a teaching hospital: lessons in leadership. PMID- 17723979 TI - Management of thrombosis in a neuro-oncology patient. PMID- 17723980 TI - Relationships among pain, fatigue, insomnia, and gender in persons with lung cancer. AB - PURPOSE/OBJECTIVES: To examine the relationships among pain, fatigue, insomnia, and gender while controlling for age, comorbidities, and stage of cancer in patients newly diagnosed with lung cancer within 56 days of receiving chemotherapy. DESIGN: Secondary data analysis. SETTING: Accrual from four sites: two clinical community oncology programs and two comprehensive cancer centers. SAMPLE: 80 patients newly diagnosed with lung cancer. METHODS: Analysis from baseline observation of a randomized clinical intervention trial. Multinomial log linear modeling was performed to explain the relationships among pain, fatigue, insomnia, and gender. MAIN RESEARCH VARIABLES: Pain, fatigue, insomnia, and gender. FINDINGS: For all people with lung cancer, fatigue (97%) and pain (69%) were the most frequently occurring symptoms; insomnia occurred 51% of the time. A model containing all main effects (two-way interactions of pain and fatigue, pain and insomnia, and insomnia and gender; and the three-way interaction of pain, fatigue, and insomnia, along with three covariates [age, comorbidities, and stage of cancer]) was a good fit to the data. Parameter estimates indicated that a statistically significant effect from the model was the three-way interaction of pain, fatigue, and insomnia. Gender did not make a difference. Age, comorbidities, and stage of cancer were not significant covariates. CONCLUSIONS: For people newly diagnosed with lung cancer undergoing chemotherapy, multiple symptoms occur simultaneously rather than in isolation; a symptom cluster exists, consisting of pain, fatigue, and insomnia; and no relationship was found among gender, pain, fatigue, and insomnia. IMPLICATIONS FOR NURSING: By understanding this symptom cluster, healthcare providers can target specific troublesome symptoms to optimize symptom management and achieve the delivery of high-quality cancer care. PMID- 17723981 TI - Oncology nurses' perceptions about palliative care. AB - PURPOSE/OBJECTIVES: To explore oncology nurses' perceptions about palliative care. RESEARCH APPROACH: Descriptive study with narrative data analysis. SETTING: Oncology units in three midwestern hospitals. PARTICIPANTS: 33 actively practicing oncology nurses. METHODOLOGIC APPROACH: Oncology nurses participated in focus groups that elicited concrete experiences and reflections about palliative care. Researchers identified subtexts by which to sort data, worked inductively in each subtext to identify categories, resorted the text according to the categories, carefully examined the category narratives, and established narrative descriptors that captured the essence of each category. Data matrices were constructed to examine the emerging categories more closely. MAIN RESEARCH VARIABLE: Oncology nurses' perceptions about palliative care. FINDINGS: Narratives revealed 14 descriptors about palliative care. Considerable agreement occurred in nurses' descriptions about the nature of palliative care. Divergent viewpoints were evident as nurses described how palliative care intersects with other practice areas. Three descriptors of the healthcare context in which palliative care occurs were identified: limited time for addressing complex palliative care issues, health care's emphasis on prolonging life, and the challenge of coordinating care across disciplines. CONCLUSIONS: Participants clearly comprehend palliative care goals. However, divergent perspectives about the intersections of palliative care with oncology nursing may limit timely consultation with specialty palliative care teams. The current acute care context poses challenges to implementing palliative care. INTERPRETATION: Palliative care teams and oncology nurses need to develop partnership models that clearly illustrate how both partners contribute to palliative care across the continuum of oncology care. Furthermore, the partnership models must address barriers that the acute care context poses to quality palliative care. PMID- 17723982 TI - Oncology End-of-Life Nursing Education Consortium training program: improving palliative care in cancer. AB - PURPOSE/OBJECTIVES: To describe an evaluation of the oncology version of the End of-Life Nursing Education Consortium (ELNEC-Oncology) training program, which is designed to provide oncology nurses with the knowledge and materials necessary to disseminate palliative care information to their colleagues in local chapters of the Oncology Nursing Society (ONS). DATA SOURCES: Participant reports. DATA SYNTHESIS: 124 nurses representing 74 ONS chapters attended the first two courses. Dyads of ONS members from local chapters applied to attend ELNEC and completed surveys regarding their goals and expectations for implementing end-of life (EOL) education and training after completion of the program. Participants educated more than 26,000 nurses after attending the program, including 7,593 nurses within their ONS chapters and 18,517 colleagues within their workplaces. Barriers to implementation included a lack of funding and time constraints. Participants sought additional palliative care learning opportunities, including attending other workshops, subscribing to palliative care journals, and becoming involved in committees focused on palliative care. CONCLUSION: The ELNEC-Oncology program is a national collaboration with ONS that provides oncology nurses with the tools and expertise to effectively disseminate palliative care content to colleagues within their local chapters and work settings. IMPLICATIONS FOR NURSING: EOL care information remains critical to the science of oncology nursing, and ELNEC-Oncology provides an effective strategy for disseminating the information. PMID- 17723983 TI - Factors affecting performance of usual activities during radiation therapy. AB - PURPOSE/OBJECTIVES: To examine factors that might affect patients' ability to perform their usual activities during radiation therapy. DESIGN: Prospective, longitudinal design. SETTING: A community hospital radiation oncology department. SAMPLE: 77 patients receiving radiation therapy for curative or adjuvant intent. METHODS: The role function mode of the Roy Adaptation Model guided the study. Participants rated the extent to which they were performing their usual activities on a scale of 0 (not at all) to 10 (all the time). Data were collected at baseline prior to starting radiation, weekly during treatment, and one month post-treatment. Cross-sectional and longitudinal regression analyses were used to capture changes in performance of usual activities over time. MAIN RESEARCH VARIABLES: Performance of usual activities, Karnofsky Performance Status (KPS), fatigue, and side effects. FINDINGS: Participants maintained relatively high performance status throughout the course of treatment. The ability to perform usual activities decreased significantly from baseline to the end of treatment. Ability to perform usual activities was highly negatively correlated with fatigue and side effects. Work, sick-leave benefits, living situation, fatigue, KPS, and comorbidities were associated with ability to perform usual activities along the trajectory of radiation therapy. CONCLUSIONS: Fatigue and side effects of treatment negatively affected patients' ability to carry out their usual activities during radiation therapy. IMPLICATIONS FOR NURSING: Management of side effects of treatment, including fatigue, and supporting patients' need to work or not work during treatment may help patients continue to perform activities that are important to them during radiation therapy. PMID- 17723984 TI - Activities of daily living in women with advanced breast cancer. AB - PURPOSE/OBJECTIVES: To detail the daily activities of women with advanced breast cancer. DESIGN: Descriptive, qualitative. SETTING: Six clinical sites in New England. Of the six sites, three were urban, one was suburban, and two were rural, with three sites being comprehensive cancer centers. SAMPLE: 84 women with a confirmed diagnosis of stage IV breast cancer with a life expectancy of four months or more. METHODS: A secondary analysis of an expressive writing intervention study control group. As part of the control writing group, participants kept handwritten activity logs for four consecutive days. Standard content analysis procedures were used to analyze the transcribed activity logs. MAIN RESEARCH VARIABLES: Activities of daily living in women with advanced breast cancer. FINDINGS: 22 codes were identified that depicted the daily activities of participants. Subsequent analysis merged the 22 codes into six themes. CONCLUSIONS: Findings demonstrated that patients with advanced breast cancer are living very full, active lives despite numerous symptoms and cancer treatments. IMPLICATIONS FOR NURSING: The study serves as a foundation for the development of interventions to enhance daily functioning. Oncology nurses should counsel women with advanced cancer regarding pacing and self-care activities. PMID- 17723985 TI - Breast Cancer Screening: Women's Experiences of Waiting for Further Testing. AB - PURPOSE/OBJECTIVES: To describe anxiety experienced by participants in a breast cancer screening program who have received an abnormal screening mammography result and are waiting for further testing and diagnosis and to identify the social support needed during this period. DESIGN: Exploratory, descriptive. SETTING: Quebec Breast Cancer Screening Program (QBCSP) participants in Montreal, Canada. SAMPLE: Nonprobability sample of 631 asymptomatic women, aged 50-69, who had abnormal screening mammogram results in the two months prior to the survey and who spoke or read French or English. METHODS: Mailed self-report questionnaire. MAIN RESEARCH VARIABLES: Anxiety, social support, and breast cancer screening. FINDINGS: Fifty-one percent of the participants were quite or very anxious at every stage of the prediagnostic phase. Seventy-five percent expressed their feelings to family and friends whose support was comforting but did not diminish participants' anxiety. Satisfaction from social support offered by healthcare professionals reduced their anxiety. CONCLUSIONS: To decrease anxiety in the prediagnostic phase, women need support from healthcare professionals during the early stage of the screening process to prevent exacerbation of their concerns. Support has to be integrated into a continuity-of care process. IMPLICATIONS FOR NURSING: Nurses can play a significant role in breast cancer screening programs. They can evaluate, at an early stage, participant anxiety and offer the appropriate social support. They also can ensure the follow-up and personalized support required while a patient awaits a diagnosis. PMID- 17723986 TI - Knowledge of hereditary prostate cancer among high-risk African American men. AB - PURPOSE/OBJECTIVES: To measure knowledge of hereditary prostate cancer in a group of high-risk African American men. DESIGN: Cross-sectional, correlational pilot study. SETTING: Four geographic sites: Detroit, MI; Houston, TX; Chicago, IL; and Columbia, SC. SAMPLE: 79 men enrolled in the African American Hereditary Prostate Cancer Study. METHODS: Telephone interviews. MAIN RESEARCH VARIABLES: Knowledge of hereditary prostate cancer. FINDINGS: Knowledge of hereditary prostate cancer was low. CONCLUSIONS: The high percentage of incorrect responses on questions that measure genetic testing, prevention, and risk based on a positive family history highlights educational needs. IMPLICATIONS FOR NURSING: A critical need exists for nurses to educate high-risk African American men about hereditary prostate cancer. PMID- 17723987 TI - The pain experience of Hispanic patients with cancer in the United States. AB - PURPOSE/OBJECTIVES: To explore Hispanic patients' cancer pain experience from a feminist perspective to find explanations for inadequate pain management. DESIGN: A qualitative online forum study. SETTING: Internet and community settings. SAMPLE: 15 Hispanic patients with cancer recruited using a convenience sampling method. METHODS: A six-month online forum was conducted using nine discussion topics, and the data were processed using a thematic analysis. MAIN RESEARCH VARIABLES: Cancer pain experience. FINDINGS: Four major themes emerged related to the following findings. The first was a lack of communication with healthcare providers regarding undermedication. The second was that women and men were enduring pain because of traditional gender roles guiding their behaviors. Third, participants placed the highest priority on family during the diagnosis and treatment process, thus setting aside their needs for pain management. The fourth theme was that participants were enduring inconvenience and unfair treatment in the U.S. healthcare system while simultaneously appreciating the treatment they had received. CONCLUSIONS: Because of cultural factors and marginalized status in the United States as Hispanics and as immigrants, most of the participants could not adequately describe and manage their pain. IMPLICATIONS FOR NURSING: Findings suggest a need for further investigation of the influences of multiple factors, including financial issues, cultural norms, and gender stereotypes, on cancer pain experience among diverse subgroups of Hispanic patients with cancer. PMID- 17723988 TI - Experiences of Japanese patients with colorectal cancer during the first six months after surgery. AB - PURPOSE/OBJECTIVES: To investigate the dynamic experience of patients who recently experienced the stressful situation of being diagnosed with colorectal cancer and undergoing surgery. RESEARCH APPROACH: A qualitative and inductive inquiry. SETTING: General hospitals in Japan. PARTICIPANTS: 12 patients who had undergone colorectal cancer surgery and had been discharged in the previous six months. METHODOLOGIC APPROACH: To inductively elicit the findings from patients' real experiences, interviews and qualitative analysis were used. MAIN RESEARCH VARIABLES: Experience of patients with colorectal cancer. FINDINGS: Three domains that symbolized experiences of patients with colorectal cancer during the first six months after surgery emerged: types of burdens, steps in accepting the cancer diagnosis, and way of living a normal life. Burdens included vulnerability, lack of control, asking for assistance or support, and a "why has this happened to me?" attitude. Way of living a normal life included resisting vulnerability, constructing a daily living routine, and asking for help. CONCLUSIONS: Although patients faced many and varied burdens, they were able to take several actions to gradually accept their cancer diagnoses and resume normal lives. INTERPRETATION: Some of the patients were sincere and skillful in asking for help to live normal lives, but others found that difficult. The present findings are significant in helping nurses provide interventions to enable patients to make use of assistance or support. PMID- 17723989 TI - Social support and psychological and physical states among Japanese women with breast cancer before and after breast surgery. AB - PURPOSE/OBJECTIVES: To investigate the relationship of social support and psychological and physical states among Japanese women with breast cancer and to compare the variables before and one year after breast surgery. DESIGN: A prospective longitudinal study. SETTING: A general hospital in northern Japan. SAMPLE: 61 Japanese women with breast cancer. METHODS: Measures were the Japanese versions of the Interpersonal Relationship Inventory, the General Health Questionnaire, and the Physical States Interview Form. Data were collected at four time points: before (time 1), three months after (time 2), six months after (time 3), and one year after (time 4) breast surgery. MAIN RESEARCH VARIABLES: Social support (support, reciprocity, and conflict), social support network, and psychological and physical states. FINDINGS: Psychological and physical states correlated significantly at all four time points. Significant correlations also were found between psychological states and support at times 2 and 4 and between psychological states and reciprocity at time 4. Repeated measures analysis of variance showed significant differences in support, reciprocity, conflict, and physical states but no significant differences in social support network or psychological states. CONCLUSIONS: The results of the study suggest that healthcare professionals need to consider social support as an important factor when helping Japanese women adjust to the diagnosis and treatment of breast cancer. IMPLICATIONS FOR NURSING: Healthcare professionals need to provide appropriate social support for Japanese women with breast cancer not only at the time of diagnosis of breast cancer but also after breast surgery. PMID- 17723990 TI - The double malnutritional burden and regional disparities in Taiwan elementary school children: survey database and reference values. AB - This special issue on the Nutrition and Health Survey in Taiwan Elementary School Children carried out during 2001-2002 (NAHSIT Children 2001-2002) portrays the current dilemma of the so-called "double nutritional burden" in Taiwanese children with papers addressing topics on the dietary characteristics, nutrition related knowledge, attitudes, and behaviors, usage of nutritional supplements, nutritional biochemistry, and various aspects of diet, nutrition, behavior, health and wellbeing in children. The emergence of a double health burden in Taiwanese children is more prevalent in the underprivileged and less urbanized communities than in metropolitan cities. The NAHSIT Children 2001-2002 survey provides age-, and gender- specific percentile values for anthropometric measurements, physiological variables like physical fitness, blood pressure and pulse, respiratory function and bone density; nutritional hematology and biochemistry. For international comparison, these reference data are tabulated in this report and the survey data are made available in the data archive system maintained by the Center for Survey Research, Academia Sinica. PMID- 17723991 TI - Nutrition and Health Survey of Taiwan Elementary School Children 2001-2002: research design, methods and scope. AB - The "Nutrition and Health Survey of Taiwan's Elementary School Children (2001 2002)" was to investigate the nutritional status, influential dietary and non dietary factors, health and development, and school performance, as well as the inter-relationships among these factors. The survey adopted a two-staged stratified, clustered probability sampling scheme. Towns and districts in Taiwan with particular ethnic and geographical characteristics were designated into 13 strata including Hakka areas, mountain areas, eastern Taiwan, the Penghu Islands, 3 northern regions, 3 central regions and 3 southern regions. Eight schools were selected from each stratum using the probabilities proportional to sizes method. Twenty-four pupils were randomly selected within each school. The survey included face-to-face interviews and health examinations. Taking seasonal effects into consideration, the face-to-face interviews were evenly allocated into each of the two semesters. A total of 2,419 face-to-face interviews and 2,475 health examinations were completed. Interview data included household information, socio demographics, 24-hour dietary recall, food frequency, dietary and nutritional knowledge, attitudes and behaviors, physical activity, medical history, oral health, pubertal development, and bone health. Health exam data included anthropometry, blood pressure, physical fitness, bone density, dental health, and blood and urine collection. SUDAAN was used to adjust sampling design effect. There were no significant differences in sibling rank and parental characteristics between respondents and non-respondents, which indicates that our survey is representative and unbiased. The results of this survey will increase our understanding on the nutrition and health status of schoolchildren and can be used to shape public health policy in Taiwan. PMID- 17723992 TI - Dietary nutrient intake and major food sources: the Nutrition and Health Survey of Taiwan Elementary School Children 2001-2002. AB - The aim of the study was to investigate nutrient intake and their dietary sources in Taiwanese children ages 6-12 years by analyzing the 24-hour recall data of 2386 participants from a nationally representative sample. Results showed that children in Taiwan were slightly lower in mean proportion of energy intake from carbohydrates (53.5% of energy intake) and higher in those from fats (30.8%) and protein (15.8%) as based on the recommendations of Department of Health in Taiwan. The mean intake of vitamins and of minerals by children was equivalent to or exceeded Daily Reference Intake of Taiwan (DRI) or other recommended standards with the exception of a seriously insufficient calcium intake and extremely high sodium intake. A substantial proportion of children in different age/gender/location strata had lower mean vitamin and mineral intake by DRI and other recommended standards. These nutrient profiles were mainly related to dietary patterns with relatively low intake of fruits, vegetables, cereals/grains, and dairy products, but high intake of the protein-rich foods, salt/sauces, and fats/oils. According to the suboptimal dietary nutrient profiles of Taiwanese children, particularly in the underprivileged areas, recommendations are made in this article for policy makers and health practitioners to consider in order to improve dietary quality of elementary school children. PMID- 17723993 TI - Nutrition knowledge, attitude, and behavior of Taiwanese elementary school children. AB - The purpose of this study is to understand nutrition knowledge, attitude, and behavior in Taiwanese elementary school children, and the relationship of these various components. The results indicated that children's knowledge was fair in nutrition basics, but poor in 'the physiological function of nutrients', 'relationships between diet/nutrients and disease', and 'the daily serving requirement for different food groups'. Children in general valued the importance of nutrition, but they did not concern the health benefit of foods in food selections. Their dietary quality was not satisfactory, and the diet of most children did not meet the recommended serving requirements for milk, vegetable, fruit, and cereals and grains groups. Positive relationships were found among nutrition knowledge, attitude, caring- about-nutrition behavior and dietary quality score. The restraint or disinhibited eating behavior of 4th to 6th graders was not serious, but a large number of children already performed some self-controlling practices to avoid obesity, but not frequently. One fourth of the students skipped meals, especially breakfast, and one quarter of 4th to 6th graders prepared their own breakfast; which may have some impact on children's diet quality. A gap was found between nutrition knowledge, attitude and eating behavior, especially vegetable and fruit consumption, indicating that the attitude toward eating for health was not strong in this age group. Future nutrition education for school children should not only include food serving requirements of food groups, but also apply appropriate theories to improve the motivation for healthy eating. PMID- 17723994 TI - The relationship between snack intake and its availability of 4th-6th graders in Taiwan. AB - The purpose of this study was to examine the relationship between the snack intake and snack availability of elementary school children. Data analyzed were from 722 4th to 6th graders' food availability and food intake questionnaires collected in the Nutrition and Health Survey in Taiwan Elementary School Children 2001-2002. The snacks commonly eaten were divided into two groups. Healthy snacks included dairy products, 100% fruit juice and fresh fruits. Unhealthy snacks included high fat/sugar snacks, cookies, candy, carbonated/sugared beverages and fast food. Structural equating modeling was used to test the models that describe the availability and intake of two snack groups. Results indicated that parents' intake and children's preference were major predictors of children intake of both healthy and unhealthy snacks. Other than that, the intake of unhealthy snacks was positively associated with "purchase by children themselves" but not the intake of healthy snacks, which was influenced predominantly by "present in home". The results support the perception that a positive family food environment is important for improving children's diet quality. To build a healthy family food environment, parents have to not only provide healthy snacks but also limit the unhealthy snacks in home. In addition to that, the role modeling of parents as eating healthy snacks instead of unhealthy snacks themselves may help children to develop similar behaviors. PMID- 17723995 TI - Dietary supplement usage among elementary school children in Taiwan: their school performance and emotional status. AB - Dietary supplement consumption practices among 2417 children (1295 boys and 1122 girls) aged 6 to 12 years in Taiwan were derived from the Nutrition and Health Survey in Taiwan Elementary School Children (NAHSIT 2001-2002). The proportion (22%) of boys and girls using supplements was equivalent. Some 77% of the child supplement takers took only one type of supplement. The top five supplements consumed were: multivitamins and minerals, calcium, vitamin C, cod-liver oil and bee propolis in that order. Children in the most urbanized southern Taiwan had the highest usage (33%), but prevalence was lowest in the mountainous areas (5%). Higher parental education level and household monthly income were associated with higher intakes. Supplement users were more competent at school; however, the frequency and number of supplement types were not related to competence. PMID- 17723997 TI - Evaluation of folate status by serum and erythrocyte folate levels and dietary folate intake in Taiwanese schoolchildren. AB - The folate status and dietary folate intake of Taiwanese schoolchildren was investigated by analysis of both serum and red blood cell (RBC) folate levels and dietary folate intake in 1105 boys and 958 girls aged 6-13 years sampled from the Nutrition and Health Survey in Taiwan Elementary School Children 2001-2002 (NAHSIT Children 2001-2002). Mean serum folate levels were 18.3+/-8.8 nmol/L (8.1+/-3.9 ng/mL) in boys and 20.3+/-9.7 nmol/L (9.0+/-4.3 ng/mL) in girls. Mean RBC folate levels were 700+/-320 nmol/L (308+/-141 ng/mL) in boys and 751+/-347 nmol/L (331+/-153 ng/mL) in girls. The prevalence of serum folate deficiency was 1.4% in boys and girls, and the prevalence of marginal serum folate deficiency (7 14 nmol/L) was 31.1% in boys and 25.8% in girls. In addition, 8.5% of boys and 7.4% girls had RBC folate deficiency (RBC folate < 318 nmol/L), and 17% of children had marginal RBC folate deficiency (RBC folate of 318-454 nmol/L). Our results suggesting that Taiwanese schoolchildren have poor folate status especially during periods of rapid growth and development such as the transition from childhood to early adolescence (boys at age 12-12.9, girls at age 11-12.9). The average estimated folate intakes were 269+/-9 microg/d in boys and 259+/-9 microg/d in girls, and 42% of Taiwanese schoolchildren had a dietary folate intake below 2/3 of the RDA, indicating a poor dietary folate intake in this population. This study shows that the folate status of Taiwanese schoolchildren is currently inadequate and strategies are needed for improvement. PMID- 17723996 TI - Thiamin and riboflavin status of Taiwanese elementary schoolchildren. AB - In The Nutrition and Health Survey of Taiwan Elementary School Children (NAHSIT Children 2001~2002), erythrocyte activity coefficients of transketolase (ETKAC) and glutathione reductase (EGRAC) were chosen as indices for assessing the functional status of thiamin and riboflavin nutriture. Mean values of the ETKAC for boys and girls, both of which were in a normal range, were 1.07+/-0.00 and 1.06+/-0.01, respectively. The respective prevalence rates of marginal and deficient thiamin states were 10.4% and 7.8% for boys and 9.3% and 7.3% for girls. Mean values of the EGRAC were 1.18+/-0.00 for boys and 1.19+/-0.01 for girls, both of which showed an increasing trend with age. The respective rates of marginal and deficient riboflavin states were as high as 32.5% and 3.5% for boys and 35.9% and 4.5% for girls. The marginal and deficient riboflavin statuses of Taiwanese schoolchildren were associated with a low frequency of dairy food consumption and an elevated risk of anemia. PMID- 17723998 TI - Magnesium deficiency and its lack of association with asthma in Taiwanese elementary school children. AB - The purpose of this study was to investigate magnesium nutritional status and its association with asthma in elementary school children (1277 boys and 1109 girls) participating in the Nutrition and Health Survey in Taiwan (NAHSIT children 2001 2002). Dietary magnesium intake was based on 24-hour dietary recalls. Serum magnesium was measured. Average magnesium intake was 247 mg and 228 mg for the boys and girls, respectively, which is equivalent to 135-123% of the relevant Taiwanese Dietary Reference Intakes (DRIs). Mean serum magnesium concentration was 0.87 mmol/L and 0.86 mmol/L, respectively. The prevalence of serum magnesium <0.8 mmol/L was 10.5-13.5% in both gender in our sample of elementary school children. In Taiwan, asthma was diagnosed in about 5.8% and 4.7% of boys and girls, respectively. In this study, there were no associations between asthma prevalence, dietary magnesium and serum magnesium concentration. In about 40% of our sample of school children, however, dietary magnesium may be suboptimal. This deficit should be targeted though improved intake of magnesium-rich foods such as whole grains, green vegetables and soybean products, particularly in Taiwanese school children whose dietary intakes are below the DRIs and/or who have low serum magnesium levels. PMID- 17723999 TI - Bone mass status of school-aged children in Taiwan assessed by quantitative ultrasound: the Nutrition and Health Survey in Taiwan Elementary School Children (NAHSIT Children 2001-2002). AB - Bone health status in childhood and adolescence may be important factors influencing the attainment of peak bone mass. The Nutrition and Health Survey in Taiwan Elementary School Children 2000-2001 was carried out to evaluate the overall nutrition and health status of school children aged between 6 and 13 years. The survey was conducted using a multi-stage complex sampling scheme. Townships and city districts in Taiwan were classified into 13 strata. Bone mass measured as broadband ultrasound attenuation was taken at heel by quantitative ultrasound bone densitometry. A total of 1164 boys and 1016 girls who had complete physical examination data with ultrasound bone scan were included in the current analysis. There were no apparent differences in BUA across all strata for both genders. In both boys and girls, age, height, body weight, BMI, and intake frequencies of vegetables and fruits/juices were significantly related to BUA. Results of multivariate regression showed that age (beta=1.36, p=0.0002) and body weight (beta=0.40, p<0.0001) were significant predictors for BUA in boys, whereas in girls body weight (beta=0.47, p<0.0001), height, (beta=0.20, p=0.01), dietary phosphorus intake (beta=-0.002, p=0.038), and frequency of fruit/juice intake (beta=0.15, p=0.029) remained statistically significant. The differential effects dietary intake variables on BUA in boys and girls may be in part due to the development of puberty. It would be necessary to include levels of physical activity in future analyses for better understanding factors influencing the development of peak bone mass in Taiwanese children. PMID- 17724000 TI - Hyperuricemia and metabolic syndrome in Taiwanese children. AB - Metabolic fitness in childhood is of increasing concern in transitional and advanced economies as the metabolic syndrome (MS) is recognized more often in this age group. As the MS appears, so also does hyperuricemia. Studies in Taiwan have identified both indigenous and Chinese with high prevalence of hyperuricemia. Data (1227 boys and 1057 girls, aged 6-12) from the Nutrition and Health Survey in Taiwan Elementary School Children (NAHSIT Children 2001-2002) were used to appraise the association between uric acid (UA) and MS in children. Mean serum urate increases by age, ranging from 5.69 mg/dL to 7.11 mg/dL for boys and 5.61 mg/dL to 6.13 md/dL for girls. Boys have higher UA concentrations (6.07 mg/dL vs. 5.74 mg/dL) and hyperuricemia (UA > or = 7 mg/dL) rate (26.5% vs. 18.8%) than girls. Children of Mountain areas have higher rates of hyperuricemia (boys: 39.2%, girls: 30.1%). 5.56% of boys and 6.39% of girls were classified as having the MS by ATP III criteria. Serum urate was closely correlated with the MS parameters, and waist circumference (WC) in particular (r=0.387). WC alone accounted for 18% of variance of serum urate concentration. Both serum urate and hyperuricemia are significant risk factors for the MS (serum urate in mg/dL, OR: 1.54, 95% CI: 1.36-1.74; hyperuricemia, OR: 3.73, 95% CI: 2.47-5.62). Adjustment for age and region accentuate these relationships. Not only abdominal fatness, but also uric acid status, or both together may be of interest to public health workers and clinicians in regard to the transitional health problem of MS. PMID- 17724001 TI - Prevalence of obesity and its comorbidities among schoolchildren in Taiwan. AB - To evaluate the prevalence of obesity and its comorbidities among a representative sample of elementary schoolchildren in Taiwan, the Nutrition and Health Survey in Taiwan Elementary School Children used a stratified, multi staged complex sampling scheme. In total 2,405 children (1,290 boys and 1,115 girls) were included. The prevalence of overweight and obesity was 15.5 and 14.7% in boys and 14.4 and 9.1% in girls. With respect to geographic differences, the prevalence of obesity for boys was highest in the southern area (23.3% for the 3rd stratum) and lowest in the mountain area (4.3%). For girls, the prevalence of overweight and obesity was highest in the central area (13.0% for the 3rd stratum) and lowest in the southern area (2.6% for the 3rd stratum). The obese children had higher mean levels of blood pressure, triglyceride, low density lipoprotein-cholesterol, uric acid and serum glutamic pyruvic transaminase, but lower level of high density lipoprotein-cholesterol when compared with the normal weight children. For obese and normal weight boys, the prevalence was 12.9 % vs. 0.3 % for high blood pressure, 31.4 % vs. 19.6 % for dyslipidemia, and 6.4 % vs. 0.8 % for abnormal serum glutamic pyruvic transaminase level. In conclusion, we found that about one third of the boys and one quarter of the girls were overweight and/or obesity in Taiwan. Furthermore, the prevalence of obesity related comorbidities was significantly increased for obese and/or overweight elementary schoolchildren in the Taiwan area. PMID- 17724002 TI - The spectrum of phytoestrogens in nature: our knowledge is expanding. AB - The classical phytoestrogens, so far known, constitute a group of plant-derived compounds which include mainly isoflavones, lignans, coumestanes, stilbenes and the flavonoids quercetin and kaempherol. The discovery of many more novel estrogen-like compounds in the plant kingdom demonstrates that the spectrum of phytoestrogens in nature is expanding. The classical as well as the novel phytoestrogens show a complex mode of action via interaction with the nuclear estrogen receptor isoforms ERalpha and ERbeta, exhibiting either estrogen-agonist or estrogen-antagonist effects. Their final biological activity, assessed by cell culture assay systems, animal studies and clinical trials, depends on multiple factors such as the chemical structure of the phytoestrogen, the kind of tissue and cell type, the intrinsic estrogenic status, the route of administration, the metabolism as well as the time and the level of exposure. They are characterized by high tissue specificity and dose-dependent activity. However, although phytoestrogen intake as food or dietary supplements, in particular soya products and the isoflavones genistein and daidzein, has been associated with "health promoting effects", some data indicate increased disease risk. Evidently, phytoestrogen supplementation should be viewed with caution until further studies satisfactorily delineate the effects of individual phytoestrogens on human health and disease. PMID- 17724003 TI - Management of thyroid nodules in children and adolescents. AB - Thyroid nodules in childhood and adolescence are less prevalent but more often malignant than in adulthood. Malignant nodules are predominantly papillary cancers; benign nodules are mostly solid colloid nodules/adenomas, but can be cystic or due lymphocytic thyroiditis. Previous neck irradiation (nowadays mostly encountered in childhood cancer survivors) is a clear risk factor for developing nodules. Neck irradiation for childhood Hodgkin's disease has a relative risk of 27 for the development of thyroid nodules. Female sex, a thyroid radiation dose>or=2500 cGy, and time since irradiation of >or=10 yr are independent risk factors. This subset of patients deserves long-term follow-up. The diagnostic steps for thyroid nodules in children and adolescents are not different from those in adults. First, history and physical examination should identify risk factors for malignancy of the nodule. Second, thyroid function should be assessed by serum TSH, followed by a thyroid scan in the case of a suppressed TSH. Serum calcitonin might be measured if there is suspicion of medullary thyroid carcinoma (e.g. a family history of MEN). Thyroid ultrasound is useful, especially in guidance of FNAC for optimal results, but presently should not be used for final decisions on the benign or malignant nature of the nodule. FNAC has the highest diagnostic accuracy in recognizing malignant nodules and should be applied in all nodules>or=1 cm and in nodules<1 cm only if there is suspicion for cancer (e.g. by ultrasound characteristics). Surgery is the most cost-effective treatment option for thyroid nodules, solving the problem fast. Levothyroxine treatment has a low efficacy. Experience with other treatment options like ethanol injection or laser therapy is still limited. PMID- 17724004 TI - Differentiated thyroid cancer in children and adults: same or distinct disease? AB - Differentiated thyroid cancer (Dtc) is a rare disease, especially in children. Differences in the biology and clinical course of Dtc in children, when compared with adults, may be related both to pathogenesis as well as to clinical outcome of the disease. In childhood, the thyroid gland exhibits higher susceptibility to the carcinogenetic effect of ionizating radiation than in adulthood. Papillary thyroid cancer (Ptc) is more prevalent in children in comparison to adult patients. Among molecular events known to occur in papillary thyroid carcinoma, rEt/Ptc rearrangements exhibit higher prevalence in younger patients, while brAF mutations are very rare in this age group. cancer disease presents at a more advanced stage: 1) primary tumour at diagnosis is larger, especially in relation to the volume of the whole gland; 2) neck lymph node involvement is more commonly observed; 3) distant metastases are detected 3-4 times more frequently than in adults. the lungs are almost the sole distant metastatic site in children and pulmonary metastases are nearly always functional. Additionally, recurrence rates tend to be higher in children; nevertheless, cause-specific cancer mortality remains low. Up to now, thyroid cancer guidelines have been formulated on the basis of experience gained in the general population of patients. the peculiarities in childhood disease raise the question of whether it should be considered a distinct subtype, with specifically tailored therapy recommendations. A definitive answer to this question is not possible with the present state of knowledge. In the opinion of the authors, molecular analyses of childhood thyroid cancer may be crucial, as the clinical data have not satisfactorily answered this question. PMID- 17724005 TI - Early onset adiposity: a pathway to polycystic ovary syndrome in adolescents? AB - Polycystic Ovary Syndrome is a heterogenous syndrome of unknown causation commonly associated with obesity. The particular timing of the onset of obesity may be important, since the earlier the onset of obesity the greater the severity of the metabolic and hormonal aberrations. Early postnatal life and peripubertal periods may be critical windows for the development of the "adiposity insult". The interaction of adiposity with genetic traits as well as with prenatal environmental factors may further aggravate the metabolic and endocrine abnormalities, which become more pronounced in adolescence. PMID- 17724007 TI - Galectin-3 as a marker distinguishing functioning from silent corticotroph adenomas. AB - OBJECTIVE: Galectin-3 (Gal-3) belongs to the family of carbohydrate-binding proteins with high affinity for galactoside and is involved in many biological processes including cell growth and differentiation, cell adhesion, tumor progression, apoptosis and metastasis. The aim of this study was to disclose differences in the expression of Gal-3 in silent and functioning corticotroph pituitary adenomas. DESIGN: We examined 30 pituitary adenomas (19 functioning corticotroph, 11 silent corticotroph adenomas). Two prolactinomas and 2 functioning somatotroph adenomas served as positive controls. Antigen retrieval was done by three-minute incubation via pressure boiler in citrate buffer solution, pH 6.0. A polymer was used as a secondary link to DAB chromogen. The independent variables t-test was used for comparison of the mean expression of Gal-3 in the two different corticotroph adenoma subgroups. RESULTS: Eighteen of the functioning corticotroph adenomas (94.73%) were positive for Gal-3 with a cytoplasmic and focally membranous distribution; two cases also exhibited nuclear expression, whereas 9 of the silent corticotroph adenomas (81.81%) had zero or<1% expression of Gal-3 (p=0.001). CONCLUSIONS: Gal-3 is highly expressed in functioning corticotroph adenomas of the pituitary gland, while silent adenomas exhibit very focal to null expression of Gal-3. This observation can be used in the pathological diagnosis to separate functioning from silent corticotroph adenomas of the pituitary. PMID- 17724006 TI - Contribution of endocrine parameters in predicting outcome of multiple trauma patients in an intensive care unit. AB - OBJECTIVE: To evaluate whether tentative prognostic models for intensive care unit survival of multiple trauma patients could be improved by including endocrine parameters. DESIGN: Prospective study. PATIENTS: Eighty-three male and 11 female multiple trauma patients. MEASUREMENTS: Upon admission, severity of trauma was assessed with the Acute Physiology and Chronic Health Evaluation II (APACHE II), the Sequential Organ Failure Assessment (SOFA) score and the Injury Severity Score (IS). Concurrently, blood was drawn to measure thyrotropin (TSH), free thyroxine (fT4), trioodothyronine (T3), corticotropin (ACTH), prolactin (PRL), cortisol and dehydroepiandrosterone sulphate (DHEAS). Adrenal reserve was assessed with the Synacthen test. RESULTS: Seventy-five of the 83 men and 8 of the 11 women survived. APACHE II and SOFA scores were higher in non-survivors compared to survivors (with considerable overlap). From the baseline endocrine work-up, survivors had higher ACTH and DHEAS values compared to non-survivors (also with considerable overlap). No differences between survivors and non survivors were noted in the Synacthen test or in thyroid function tests. Nevertheless, a multivariate logistic regression model that incorporated the APACHE II score and hormonal parameters (Cortisol post-Synacthen, DHEAS, TSH*age) was well-fitted to assess survival/non-survival as an endpoint and better than APACHE II, SOFA or IS scores alone to predict ICU survival or death. CONCLUSION: In critically ill multiple trauma patients, age, TSH, Cortisol post-Synacthen and DHEAS values upon admission to the ICU, combined with the APACHE II score, may predict outcome more accurately than the APACHE II score alone.an the APACHe II score alone. PMID- 17724009 TI - Cushing's syndrome in pregnancy: report of a case and review of the literature. AB - Cushing's syndrome (CS) during pregnancy is a rare nosology with only a few cases reported in the literature. Misdiagnosis is common, as the syndrome may be easily confused with preeclampsia or gestational diabetes. CS during pregnancy is usually associated with severe maternal and fetal complications. A high degree of clinical awareness is therefore required to avoid miscarriage or premature delivery. We report an 18-year old female referred to our institution with amenorrhea and truncal obesity. Physical examination revealed cushingoid characteristics, including mild hypertension (130/100 mmHg). She was also found to be 8 weeks pregnant. A provisional diagnosis of CS was made based on plasma cortisol and adrenocorticotropin hormone (ACTH) measurements but the patient did not receive any relevant therapy. She eventually gave birth to a healthy full term infant via vaginal delivery. A right adrenal adenoma was diagnosed post labor and was subsequently treated with surgical resection. The patient's condition remained stable and 19 months after the adrenalectomy she gave birth to a second healthy full-term infant. Hydrocortisone (30 mg/day) was administered throughout the second gestation. Six months post-labor the treatment was discontinued after a normal hypothalamic-pituitary-adrenal (HPA) axis was ascertained. PMID- 17724008 TI - Oral bisphosphonate adverse effects in 849 patients with metabolic bone diseases. AB - OBJECTIVE: Bisphosphonates are potent antiresorptive agents used for a spectrum of metabolic bone diseases. The aim of this study was to compare the adverse effects (AEs) of alendronate, etidronate and risedronate prescribed in a non selected population, attending a single institution on an outpatient basis. DESIGN: 849 patients receiving either alendronate (n=710), etidronate (n=181) or risedronate (n=130) were studied for a period of 1916 person-years. RESULTS: AEs were reported by 25.2% [21% gastrointestinal (GI) system-related], 11.1% (9.9%) and 20.8% (15.4%) of patients on alendronate/etidronate/risedronate, respectively, resulting in permanent discontinuation in 21.0%, 7.7% and 13.8%, respectively. The odds ratio (95% Ci) for AEs in the case of a history of gi disease was 2.4 (1.4-3.8), 2.1 (0.8-5.1) and 2.5 (0.9-6.6), respectively. The majority of AEs were of a mild nature and usually occurred within six months of therapy initiation. The odds ratio for AEs given the concurrent use of NSAIDS was 2.0 (1.4-3.0), 0.8 (0.3-2.4) and 2.2 (0.8-5.9), respectively. CONCLUSIONS: Etidronate appears to have a better Ae profile. Bisphosphonate AEs are fairly mild, affect the gi system, occur most frequently in the presence of gi disease or concurrent use of NSAIDS and tend to be of the same type in the event of administration of a different bisphosphonate. PMID- 17724010 TI - Growth hormone deficiency in a patient with autoimmune polyendocrinopathy type 2. AB - Autoimmune polyglandular syndrome (APs) type 2 is characterized by the presence of Addison's disease, in association with autoimmune thyroid disease and/or type 1 diabetes mellitus and is rare in children. A 12.5 yr old prepubertal boy presented with symptoms related to Addison's disease and a large goiter. He was euthyroid with positive thyroid antibodies, low cortisol, aldosterone and very high adrenocorticotropin (ActH) and renin levels. Growth hormone (GH) secretion and an MrI scan of the pituitary were normal. He was started on hydrocortisone, fludrocortisone and subsequently on L thyroxine. Eighteen months later, decreased growth rate was noted and GH deficiency was detected, apparently secondary to autoimmune hypophysitis. Interestingly, he did not develop any other pituitary hormone deficiencies. He was started on GH therapy and had a good treatment response in the next 3 years. the combination of adrenal and thyroid insufficiencies with autoimmune hypophysitis is a very rare manifestation of APs type 2. GH deficiency as the only symptom of lymphocytic hypophysitis is extremely rare. In children with autoimmune polyendocrine disorders, careful monitoring of growth is needed. In the case of low growth rate, GH should be evaluated by dynamic tests and, if GH deficiency is detected, treatment with hGH must be initiated. PMID- 17724011 TI - Brunner's missing 'Aha experience' delayed progress in diabetes research by 200 years. AB - In 1889, the pancreatectomy performed on a dog by Joseph von Mehring and Oskar Minkowski led to the discovery of the pancreatic origin of diabetes disease. Already 200 years before, Johann Conrad Brunner had successfully performed eight pancreatectomies on dogs and had precisely described the symptoms of polyphagia, polyuria, and polydipsia. He did not, however, recognize the association with the diabetes disease and thus missed an opportunity to accelerate the course of diabetes research by 200 years. PMID- 17724012 TI - Islet cell dysfunction in progression to diabetes mellitus. AB - The epidemic of type 2 diabetes mellitus is increasing in most nations. This illness is a major cause of cardiovascular disease, stroke, blindness, renal failure, and amputations. Because available interventions have failed to show durability, new modes of therapy need to be directed at the underlying causes of abnormal glucose metabolism. The development of such modes of therapy will require an improved understanding of how the beta-cell mass compensates for changes in insulin resistance and why beta cells lose the capacity to secrete insulin. In addition, new therapeutic modalities need to address alpha-cell dysregulation, because the inability to suppress glucagon production results in ongoing elevated levels of hepatic glucose. PMID- 17724013 TI - Application of incretin mimetics and dipeptidyl peptidase IV inhibitors in managing type 2 diabetes mellitus. AB - Approximately two thirds of patients with type 2 diabetes mellitus (T2DM) are unable to reach the hemoglobin A(1c) target set by the American Diabetes Association (HbA(1c) <7.0%). Therefore, T2DM continues to be a major public health concern. Incretin mimetics and dipeptidyl peptidase IV inhibitors are medications that have the potential to improve patients' glycemic control, as well as to result in beneficial socioeconomic effects. Research suggests that significant benefits are to be gained from incretin mimetics and dipeptidyl peptidase IV inhibitors, either one used as monotherapy or used together as combination therapy. However, the benefits and risks of these agents need to be evaluated more thoroughly, with emphasis on such adverse effects as edema, hypoglycemia, and weight gain. PMID- 17724014 TI - The pathophysiologic role of incretins. AB - Many patients with type 2 diabetes mellitus (T2DM) are unable to achieve adequate glycemic control. Of the approximately 19 million individuals with T2DM in the United States, only about a third achieve the hemoglobin A(1c) (HbA(1c)0 goal set forth by the American Diabetes Association (HbA(1c) <7% [6% if it can be achieved safely]). The incretin mimetics are a new class of medications available for treating patients with T2DM. They mimic the action of incretins, which are peptide hormones that originate in the gastrointestinal tract. The two major incretins in humans are glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). These hormones are released during nutrient absorption, augmenting insulin secretion. However, incretins are susceptible to degradation by dipeptidyl peptidase IV (DPP-IV). Dipeptidyl peptidase IV inhibitors suppress the degradation of incretins, thus extending the activity of GLP-1 and GIP. The glycemic profiles of patients after administration of incretin mimetics and DPP-IV inhibitors show improvement in postprandial glucose levels and ultimately in HbA(1c). Therefore, incretin mimetics and DPP-IV inhibitors may play a clinically significant role in the treatment of patients with T2DM. PMID- 17724015 TI - Transcription termination factor rho can displace streptavidin from biotinylated RNA. AB - In Escherichia coli, binding of the hexameric Rho protein to naked C-rich Rut (Rho utilization) regions of nascent RNA transcripts initiates Rho-dependent termination of transcription. Although the ring-shaped Rho factor exhibits in vitro RNA-dependent ATPase and directional RNA-DNA helicase activities, the actual molecular mechanisms used by Rho to disrupt the intricate network of interactions that cement the ternary transcription complex remain elusive. Here, we show that Rho is a molecular motor that can apply significant disruptive forces on heterologous nucleoprotein assemblies such as streptavidin bound to biotinylated RNA molecules. ATP-dependent disruption of the biotin-streptavidin interaction demonstrates that Rho is not mechanistically limited to the melting of nucleic acid base pairs within molecular complexes and confirms that specific interactions with the roadblock target are not required for Rho to operate properly. We also show that Rho-induced streptavidin displacement depends significantly on the identity of the biotinylated transcript as well as on the position, nature, and length of the biotin link to the RNA chain. Altogether, our data are consistent with a "snow plough" type of mechanism of action whereby an early rearrangement of the Rho-substrate complex (activation) is rate-limiting, physical force (pulling) is exerted on the RNA chain by residues of the central Rho channel, and removal of structural obstacles from the RNA track stems from their nonspecific steric exclusion from the hexamer central hole. In this context, a simple model for the regulation of Rho-dependent termination based on the modulation of disruptive dynamic loading by secondary factors is proposed. PMID- 17724017 TI - Critical role of helix 4 of HIV-1 capsid C-terminal domain in interactions with human lysyl-tRNA synthetase. AB - Human tRNALys3 is used as the primer for human immunodeficiency virus type 1 (HIV 1) reverse transcription. HIV-1 Gag and GagPol, as well as host cell factor lysyl tRNA synthetase (LysRS), are required for specific packaging of tRNALys into virions. Gag alone is sufficient for packaging of LysRS, and these two proteins have been shown to interact in vitro with an equilibrium binding constant of approximately 310 nM. The capsid (CA) domain of Gag binds to LysRS with a similar affinity as full-length Gag. In this work, we report further characterization of the interaction between HIV-1 CA and human LysRS using truncation constructs and point mutations in the putative interaction helices. Fluorescence anisotropy binding measurements reveal that a LysRS variant lacking the N-terminal 219 residues still displays high affinity binding to CA. The CA C-terminal domain (CTD) is also sufficient for binding to LysRS. Nuclear magnetic resonance spectroscopy studies using 15N-labeled CA-CTD reveal chemical shift perturbations of residues in and proximal to helix 4 of CA-CTD upon LysRS binding. A synthetic peptide that includes helix 4 binds to LysRS with high affinity, whereas peptides derived from the other three helical domains of CA-CTD do not. Alanine-scanning mutagenesis studies targeting residues in the helix 4 region support a direct interaction between this domain of CA-CTD and LysRS. The high resolution mapping studies reported here will facilitate future work aimed at disrupting the Gag LysRS interaction, which represents a novel anti-viral strategy. PMID- 17724016 TI - Basic fibroblast growth factor activates the MAPK and NFkappaB pathways that converge on Elk-1 to control production of matrix metalloproteinase-13 by human adult articular chondrocytes. AB - The pathology of joint destruction is associated with elevated production of basic fibroblast growth factor (bFGF) and matrix metalloproteinase-13 (MMP-13). In osteoarthritic joint disease, expression of bFGF and MMP-13 in chondrocytes and their release into the synovial fluid are significantly increased. We have previously found that the capacity for cartilage repair in human adult articular chondrocytes is severely compromised by minimal exposure to bFGF because bFGF reduces responsiveness to bone morphogenetic protein-7 and insulin-like growth factor-1 and induces MMP-13 through protein kinase Cdelta-dependent activation of multiple mitogen-activated protein kinase (MAPK) signaling pathways. Here we show using biochemical and molecular approaches that transcription factor Elk-1, a direct downstream target of MAPK, is a critical transcriptional activator of of MMP-13 by bFGF in human articular chondrocytes. We also provide evidence that Elk 1 is a direct target of NFkappaB and induces MMP-13 expression upon activation of the NFkappaB signaling pathway. Taken together, our results suggest that elevated expression of MMP-13 occurs through Elk-1 activation of both MAPK and NFkappaB signaling pathways, thus revealing a two-pronged biological mechanism by which bFGF controls the production of catabolic enzymes that are associated with excessive degradation of the cartilage matrix in degenerative joint diseases such as osteoarthritis. PMID- 17724018 TI - Gestational choline deficiency causes global and Igf2 gene DNA hypermethylation by up-regulation of Dnmt1 expression. AB - During gestation there is a high demand for the essential nutrient choline. Adult rats supplemented with choline during embryonic days (E) 11-17 have improved memory performance and do not exhibit age-related memory decline, whereas prenatally choline-deficient animals have memory deficits. Choline, via betaine, provides methyl groups for the production of S-adenosylmethionine, a substrate of DNA methyltransferases (DNMTs). We describe an apparently adaptive epigenomic response to varied gestational choline supply in rat fetal liver and brain. S Adenosylmethionine levels increased in both organs of E17 fetuses whose mothers consumed a choline-supplemented diet. Surprisingly, global DNA methylation increased in choline-deficient animals, and this was accompanied by overexpression of Dnmt1 mRNA. Previous studies showed that the prenatal choline supply affects the expression of multiple genes, including insulin-like growth factor 2 (Igf2), whose expression is regulated in a DNA methylation-dependent manner. The differentially methylated region 2 of Igf2 was hypermethylated in the liver of E17 choline-deficient fetuses, and this as well as Igf2 mRNA levels correlated with the expression of Dnmt1 and with hypomethylation of a regulatory CpG within the Dnmt1 locus. Moreover, mRNA expression of brain and liver Dnmt3a and methyl CpG-binding domain 2 (Mbd2) protein as well as cerebral Dnmt3l was inversely correlated to the intake of choline. Thus, choline deficiency modulates fetal DNA methylation machinery in a complex fashion that includes hypomethylation of the regulatory CpGs within the Dnmt1 gene, leading to its overexpression and the resultant increased global and gene-specific (e.g. Igf2) DNA methylation. These epigenomic responses to gestational choline supply may initiate the long term developmental changes observed in rats exposed to varied choline intake in utero. PMID- 17724019 TI - Reinvestigation of a selenopeptide with purportedly high glutathione peroxidase activity. AB - A 15-amino acid long selenopeptide (15SeP) was recently reported to possess nearly the same catalytic activity as glutathione peroxidase (Gpx) for the reduction of hydrogen peroxide by glutathione (Sun, Y., Li, T. Y., Chen, H., Zhang, K., Zheng, K. Y., Mu, Y., Yan, G. L., Li, W., Shen, J. C., and Luo, G. M. (2004) J. Biol. Chem. 279, 37235-37240). Such a finding is startling considering the high efficiency of the natural enzyme and the modest catalytic properties of most short peptides. As 15SeP had been subjected only to limited chemical characterization, we prepared it by a new route involving selenocysteine-mediated native chemical ligation. High resolution matrix-assisted laser desorption ionization mass spectrometry confirmed the identity of the reaction product, whereas circular dichroism spectroscopy showed that 15SeP assumes a random coil conformation in solution. Although low levels of peroxidase activity were detectable under standard assay conditions, the peptide is >5 orders of magnitude less active than native Gpx. Our observations are incompatible with claims ascribing remarkable catalytic properties to 15SeP and suggest that the efficiency of Gpx derives from its well defined three-dimensional structure. PMID- 17724020 TI - S-adenosylmethionine-dependent protein methylation in mammalian cytosol via tyrphostin modification by catechol-O-methyltransferase. AB - It has previously been shown that incubation of mammalian cell cytosolic extracts with the protein kinase inhibitor tyrphostin A25 results in enhanced transfer of methyl groups from S-adenosyl-[methyl-3H]methionine to proteins. These findings were interpreted as demonstrating tyrphostin stimulation of a novel type of protein carboxyl methyltransferase. We find here, however, that tyrphostin A25 addition to mouse heart cytosol incubated with S-adenosyl-[methyl-3H]methionine or S-adenosyl-[methyl-14C]methionine stimulates the labeling of small molecules in addition to proteins. Base treatment of both protein and small molecule fractions releases volatile radioactivity, suggesting labile ester-like linkages of the labeled methyl group. Production of both the base-volatile product and labeled protein occurs with tyrphostins A25, A47, and A51, but not with thirteen other tyrphostin family members. These active tyrphostins all contain a catechol moiety and are good substrates for recombinant and endogenous catechol-O methyltransferase. Inhibition of catechol-O-methyltransferase activity with tyrphostin AG1288 prevents both base-volatile product formation and protein labeling from methyl-labeled S-adenosylmethionine in heart, kidney, and liver, but not in testes or brain extracts. These results suggest that the incorporation of methyl groups into protein follows a complex pathway initiated by the methylation of select tyrphostins by endogenous catechol-O-methyltransferase. We suggest that the methylated tyrphostins are further modified in the cell extract and covalently attached to cellular proteins. The presence of endogenous catechols in cells suggests that similar reactions can also occur in vivo. PMID- 17724021 TI - Cystic fibrosis transmembrane conductance regulator-independent phagosomal acidification in macrophages. AB - It was reported recently that the cystic fibrosis transmembrane conductance regulator (CFTR) is required for acidification of phagosomes in alveolar macrophages (Di, A., Brown, M. E., Deriy, L. V., Li, C., Szeto, F. L., Chen, Y., Huang, P., Tong, J., Naren, A. P., Bindokas, V., Palfrey, H. C., and Nelson, D. J. (2006) Nat. Cell Biol. 8, 933-944). Here we determined whether the CFTR chloride channel is a generalized pathway for chloride entry into phagosomes in macrophages and whether mutations in CFTR could contribute to alveolar macrophage dysfunction. The pH of mature phagolysosomes in macrophages was measured by fluorescence ratio imaging using a zymosan conjugate containing Oregon Green(R) 488 and tetramethylrhodamine. Acidification of phagolysosomes in J774A.1 macrophages (pH approximately 5.1 at 45 min), murine alveolar macrophages (pH approximately 5.3), and human alveolar macrophages (pH approximately 5.3) was insensitive to CFTR inhibition by the thiazolidinone CFTR(inh)-172. Acidification of phagolysosomes in alveolar macrophages isolated from mice homozygous for DeltaF508-CFTR, the most common mutation in cystic fibrosis, was not different compared with that in alveolar macrophages isolated from wild-type mice. We also measured the kinetics of phagosomal acidification in J774A.1 and murine alveolar macrophages using a zymosan conjugate containing fluorescein and tetramethylrhodamine. Phagosomal acidification began within 3 min of zymosan binding and was complete within approximately 15 min of internalization. The rate of phagosomal acidification in J774A.1 cells was not slowed by CFTR(inh)-172 and was not different in alveolar macrophages from wild-type versus DeltaF508-CFTR mice. Our data indicate that phagolysosomal acidification in macrophages is not dependent on CFTR channel activity and do not support a proposed mechanism for cystic fibrosis lung disease involving defective phagosomal acidification and bacterial killing in alveolar macrophages. PMID- 17724022 TI - A dimeric Smac/diablo peptide directly relieves caspase-3 inhibition by XIAP. Dynamic and cooperative regulation of XIAP by Smac/Diablo. AB - Caspase activation, the executing event of apoptosis, is under deliberate regulation. IAP proteins inhibit caspase activity, whereas Smac/Diablo antagonizes IAP. XIAP, a ubiquitous IAP, can inhibit both caspase-9, the initiator caspase of the mitochondrial apoptotic pathway, and the downstream effector caspases, caspase-3 and caspase-7. Smac neutralizes XIAP inhibition of caspase-9 by competing for binding of the BIR3 domain of XIAP with caspase-9, whereas how Smac liberates effector caspases from XIAP inhibition is not clear. It is generally believed that binding of Smac with IAP generates a steric hindrance that prevents XIAP from inhibiting effector caspases, and therefore small molecule mimics of Smac are not able to reverse inhibition of the effector caspases. Surprisingly, we show here that binding of a dimeric Smac N-terminal peptide with the BIR2 domain of XIAP effectively antagonizes inhibition of caspase-3 by XIAP. Further, we defined the dynamic and cooperative interaction of Smac with XIAP: binding of Smac with the BIR3 domain anchors the subsequent binding of Smac with the BIR2 domain, which in turn attenuates the caspase-3 inhibitory function of XIAP. We also show that XIAP homotrimerizes via its C terminal Ring domain, making its inhibitory activity toward caspase-3 more susceptible to Smac. PMID- 17724023 TI - P68 RNA helicase unwinds the human let-7 microRNA precursor duplex and is required for let-7-directed silencing of gene expression. AB - MicroRNAs are short, single-stranded RNAs that arise from a transient precursor duplex. We have identified a novel activity in HeLa cell extracts that can unwind the let-7 microRNA duplex. Using partially purified material, we have shown that microRNA helicase activity requires ATP and has a native molecular mass of approximately 68 kDa. Affinity purification of the unwinding activity revealed co purification of P68 RNA helicase. Importantly, recombinant P68 RNA helicase was sufficient to unwind the let-7 duplex. Moreover, like its native homolog, P68 RNA helicase did not unwind an analogous small interfering RNA duplex. We further showed that knockdown of P68 inhibited let-7 microRNA function. From our data, we conclude that P68 RNA helicase is an essential component of the let-7 microRNA pathway, and in conjunction with other factors, it may play a role in the loading of let-7 microRNA into the silencing complex. PMID- 17724025 TI - Structure/function characterization of micro-conotoxin KIIIA, an analgesic, nearly irreversible blocker of mammalian neuronal sodium channels. AB - Peptide neurotoxins from cone snails continue to supply compounds with therapeutic potential. Although several analgesic conotoxins have already reached human clinical trials, a continuing need exists for the discovery and development of novel non-opioid analgesics, such as subtype-selective sodium channel blockers. Micro-conotoxin KIIIA is representative of micro-conopeptides previously characterized as inhibitors of tetrodotoxin (TTX)-resistant sodium channels in amphibian dorsal root ganglion neurons. Here, we show that KIIIA has potent analgesic activity in the mouse pain model. Surprisingly, KIIIA was found to block most (>80%) of the TTX-sensitive, but only approximately 20% of the TTX resistant, sodium current in mouse dorsal root ganglion neurons. KIIIA was tested on cloned mammalian channels expressed in Xenopus oocytes. Both Na(V)1.2 and Na(V)1.6 were strongly blocked; within experimental wash times of 40-60 min, block was reversed very little for Na(V)1.2 and only partially for Na(V)1.6. Other isoforms were blocked reversibly: Na(V)1.3 (IC50 8 microM), Na(V)1.5 (IC50 284 microM), and Na(V)1.4 (IC50 80 nM). "Alanine-walk" and related analogs were synthesized and tested against both Na(V)1.2 and Na(V)1.4; replacement of Trp-8 resulted in reversible block of Na(V)1.2, whereas replacement of Lys-7, Trp-8, or Asp-11 yielded a more profound effect on the block of Na(V)1.4 than of Na(V)1.2. Taken together, these data suggest that KIIIA is an effective tool to study structure and function of Na(V)1.2 and that further engineering of micro conopeptides belonging to the KIIIA group may provide subtype-selective pharmacological compounds for mammalian neuronal sodium channels and potential therapeutics for the treatment of pain. PMID- 17724024 TI - Leucine carboxyl methyltransferase-1 is necessary for normal progression through mitosis in mammalian cells. AB - Protein phosphatase 2A (PP2A) is a multifunctional phosphatase that plays important roles in many cellular processes including regulation of cell cycle and apoptosis. Because PP2A is involved in so many diverse processes, it is highly regulated by both non-covalent and covalent mechanisms that are still being defined. In this study we have investigated the importance of leucine carboxyl methyltransferase-1 (LCMT-1) for PP2A methylation and cell function. We show that reduction of LCMT-1 protein levels by small hairpin RNAs causes up to a 70% reduction in PP2A methylation in HeLa cells, indicating that LCMT-1 is the major mammalian PP2A methyltransferase. In addition, LCMT-1 knockdown reduced the formation of PP2A heterotrimers containing the Balpha regulatory subunit and, in a subset of the cells, induced apoptosis, characterized by caspase activation, nuclear condensation/fragmentation, and membrane blebbing. Knockdown of the PP2A Balpha regulatory subunit induced a similar amount of apoptosis, suggesting that LCMT-1 induces apoptosis in part by disrupting the formation of PP2A(BalphaAC) heterotrimers. Treatment with a pan-caspase inhibitor partially rescued cells from apoptosis induced by LCMT-1 or Balpha knockdown. LCMT-1 knockdown cells and Balpha knockdown cells were more sensitive to the spindle-targeting drug nocodazole, suggesting that LCMT-1 and Balpha are important for spindle checkpoint. Treatment of LCMT-1 and Balpha knockdown cells with thymidine dramatically reduced cell death, presumably by blocking progression through mitosis. Consistent with these results, homozygous gene trap knock-out of LCMT-1 in mice resulted in embryonic lethality. Collectively, our results indicate that LCMT-1 is important for normal progression through mitosis and cell survival and is essential for embryonic development in mice. PMID- 17724026 TI - Protein kinase C zeta. A novel regulator of both phosphorylation and de phosphorylation of cardiac sarcomeric proteins. AB - Our experiments investigated associations of specific isoforms of protein kinase C (PKC) with individual proteins in the cardiac troponin complex. Troponin I (cTnI) associated with PKCepsilon and zeta and troponin T (cTnT) associated with PKC alpha, delta, and epsilon. Based on its association with cTnI, we hypothesized that PKCzeta is a major regulator of myofilament protein phosphorylation. To test this, we infected adult cardiac myocytes with adenoviral constructs containing DsRed monomer-tagged wild type (WT) and the following constitutively active forms of PKCzeta: the pseudo-substrate region (A119E), 3' phospho-inositide-dependent kinase-1 (T410E), and auto-phosphorylation (T560E). The A119E and T410E mutants displayed increased localization to the Z-discs compared with WT and T560E. Immunoprecipitations were performed in myocytes expressing PKCzeta using PKC phospho-motif antibodies to determine the phosphorylation of cTnI, cTnT, tropomyosin, myosin-binding protein C, and desmin. We did not find serine (Ser) phosphorylation of cTnI or cTnT. However, we observed a significant decrease in threonine (Thr) phosphorylation of cTnI and cTnT notably by PKCzeta T560E. Ser phosphorylation of tropomyosin was increased by all three active mutants of PKCzeta. Ser/Thr phosphorylation of myosin-binding protein C increased primarily by PKCzeta A119E. Both PKCzeta A119E and T410E mutants increased desmin Ser/Thr phosphorylation. To explain the apparent Thr dephosphorylation of cTnI and cTnT, we hypothesized that PKCzeta exists as a complex with p21-activated kinase-1 (Pak1) and protein phosphatase 2A (PP2A), and this was confirmed by immunoprecipitation Western blot. Our data demonstrate that PKCzeta is a novel regulator of myofilament protein phosphorylation. PMID- 17724028 TI - Feasibility of pathways for transfer of acyl groups from mitochondria to the cytosol to form short chain acyl-CoAs in the pancreatic beta cell. AB - The mitochondria of pancreatic beta cells are believed to convert insulin secretagogues into products that are translocated to the cytosol where they participate in insulin secretion. We studied the hypothesis that short chain acyl CoA (SC-CoAs) might be some of these products by discerning the pathways of SC CoA formation in beta cells. Insulin secretagogues acutely stimulated 1.5-5-fold increases in acetoacetyl-CoA, succinyl-CoA, malonyl-CoA, hydroxymethylglutaryl CoA (HMG-CoA), and acetyl-CoA in INS-1 832/13 cells as judged from liquid chromatography-tandem mass spectrometry measurements. Studies of 12 relevant enzymes in rat and human pancreatic islets and INS-1 832/13 cells showed the feasibility of at least two redundant pathways, one involving acetoacetate and the other citrate, for the synthesis SC-CoAs from secretagogue carbon in mitochondria and the transfer of their acyl groups to the cytosol where the acyl groups are converted to SC-CoAs. Knockdown of two key cytosolic enzymes in INS-1 832/13 cells with short hairpin RNA supported the proposed scheme. Lowering ATP citrate lyase 88% did not inhibit glucose-induced insulin release indicating citrate is not the only carrier of acyl groups to the cytosol. However, lowering acetoacetyl-CoA synthetase 80% partially inhibited glucose-induced insulin release indicating formation of SC-CoAs from acetoacetate in the cytosol is important for insulin secretion. The results indicate beta cells possess enzyme pathways that can incorporate carbon from glucose into acetyl-CoA, acetoacetyl CoA, and succinyl-CoA and carbon from leucine into these three SC-CoAs plus HMG CoA in their mitochondria and enzymes that can form acetyl-CoA, acetoacetyl-CoA, malonyl-CoA, and HMG-CoA in their cytosol. PMID- 17724027 TI - Glutathione depletion is necessary for apoptosis in lymphoid cells independent of reactive oxygen species formation. AB - Changes in the intracellular redox environment of cells have been reported to be critical for the activation of apoptotic enzymes and the progression of programmed cell death. Glutathione (GSH) depletion is an early hallmark observed in apoptosis, and we have demonstrated that GSH efflux during death receptor mediated apoptosis occurs via a GSH transporter. We now evaluate the relationship between GSH depletion, the generation of reactive oxygen species (ROS), and the progression of apoptosis. Simultaneous single cell analysis of changes in GSH content and ROS formation by multiparametric FACS revealed that loss of intracellular GSH was paralleled by the generation of different ROS including hydrogen peroxide, superoxide anion, hydroxyl radical, and lipid peroxides. However, inhibition of ROS formation by a variety of antioxidants showed that GSH loss was independent from the generation of ROS. Furthermore, GSH depletion was observed to be necessary for ROS generation. Interestingly, high extracellular thiol concentration (GSH and N-acetyl-cysteine) inhibited apoptosis, whereas, inhibition of ROS generation by other non-thiol antioxidants was ineffective in preventing cell death. Finally, GSH depletion was shown to be a necessary for the progression of apoptosis activated by both extrinsic and intrinsic signaling pathways. These results document a necessary and critical role for GSH loss in apoptosis and clearly uncouple for the first time GSH depletion from ROS formation. PMID- 17724029 TI - Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, suppresses hepatic gluconeogenesis through 5'-AMP-activated protein kinase. AB - Epigallocatechin-3-gallate (EGCG), a main catechin of green tea, has been suggested to inhibit hepatic gluconeogenesis. However, the exact role and related mechanism have not been established. In this study, we examined the role of EGCG in hepatic gluconeogenesis at concentrations that are reachable by ingestion of pure EGCG or green tea, and are not toxic to hepatocytes. Our results show in isolated hepatocytes that EGCG at relatively low concentrations ( 32 pmol/l (=300 ng/l). Patients with failing transplants are less likely to achieve RA targets of key biochemical variables when compared to patients on dialysis. There is still wide variability in the completeness of data returns from individual units. PMID- 17724043 TI - Survival of incident RRT patients in the UK (chapter 12). AB - This analysis presents the survival of patients starting renal replacement therapy (RRT) in UK renal units ('centres'), and includes an analysis of survival by centre. Data from 59 of the 70 UK centres are included. This is the first year that UK centre anonymity has been removed from analysis of patient survival by centre. Survival after adjustment for comorbidity is also reported for the first time although this analysis is restricted to those centres returning data on comorbidity in at least 85% of incident patients. The importance of adjusting for comorbidity can be seen in that for one centre, after adjustment of survival for age and diagnosis, the adjusted 1 year after 90 day survival was 84.6%. After adjusting to the average comorbidity present across centres, survival increased to 90.4%. Improved comorbidity data returns by renal units may require investment in informatics staff and creating structural process at renal unit level for clinicians to support these data returns. From the date of first RRT, the 1 year survival of all patients (unadjusted for age) is 79%. From the 90th day of RRT (to allow comparison with other countries' 1 year survival), the 1 year survival is 83%. The age adjusted (60 years) survival for the 1 year after 90 day period is 86%. There is a high death rate in the first 90 days on RRT (6% of all patients starting RRT), a period not included in reports by many registries and other studies. The 5 year survival (including deaths within the first 90 days) rates are 58, 53, 44, 28, 19 and 12%, respectively for patients aged 18-34, 35 44, 45-54, 55-64, 65-74 and >75 years. The 'vintage effect' of increasing hazard of death with length of time on RRT, prominent in data from the US, is only noted in older age groups (65-75 and 75+ years) at 5-6 years after starting RRT. Six centres had a figure for the 1 year after 90 day survival which was outside 2 SDs from the mean for the UK: in three cases this was better survival, and in three, poorer survival, than expected. Poor reporting by renal units of patient comorbidity makes interpretation of these apparent differences in patient survival between centres difficult and a relationship to clinical performance cannot yet be inferred. PMID- 17724044 TI - Demography and management of childhood established renal failure in the UK (chapter 13). AB - The incidence and prevalence of ERF in children in the UK are relatively static at 8.0 and 47.7 per million population under the age of 15 years, respectively. The prevalence of ERF in children from the South Asian community is almost three times that of the White population whilst the incidence is over three times that of the White population and similar to the increase seen in the adult population. The high incidence and prevalence are related to the high incidence of inherited diseases which cause ERF in the South Asian community. ERF in children is more common in males than females (male to female ratio 1.54:1). This is due to a preponderance of males with renal dysplasia and obstructive uropathy causing ERF. For the South Asian patients, the gender ratio is 1:1 as the inherited diseases are mainly autosomal recessive. Renal dysplasia is the single most common cause of ERF in childhood, followed closely by glomerular disorders and then obstructive uropathy. The majority of prevalent paediatric ERF patients (76%) have a renal allograft. Of these, 28% are from living donations. The proportion of patients from ethnic minority groups with a functioning allograft is significantly smaller than that in the White population (P < 0.0001). Despite this, the rate of living related donation is no higher in the ethnic minority population. In prevalent patients PD is twice as commonly used as HD with the majority managed with automated PD. For patients at one year from starting RRT, 49% are on PD, 10% on HD and 41% have a transplant. PMID- 17724045 TI - Growth in children with established renal failure--a Registry analysis (chapter 14). AB - Short stature is a major problem in paediatric ERF patients with 29% of transplant patients and 41% of dialysis patients below the second percentile for height. Only 6.5% of transplant patients and 15.5% of dialysis patients are receiving rhGH. There is no significant difference in the height distribution of patients commencing RRT and those who have had a functioning allograft for at least 1 year. In patients with at least 2 years between presentation and RRT, there is a significant fall in height Z score. This overall statistic is strongly influenced by the very poor growth of patients with glomerular disease. PMID- 17724047 TI - The Renal Long Term Care Workforce Survey (in conjunction with the British Renal Society) (chapter 16). PMID- 17724046 TI - Aspects of anaemia management in children with established renal failure (chapter 15). AB - Despite the universal availability of erythropoietin and intravenous iron, 14% of transplant patients and 30% of dialysis patients have a haemoglobin (Hb) <10.5 g/dl. Only 11% of anaemic transplant patients were receiving erythropoietin. There was a linear relationship between estimated glomerular filtration rate (eGFR) and Hb with the risk of anaemia occurring at a much higher eGFR than would be expected in the chronic kidney disease (CKD) population. There was also a significant association between the use of mycophenolate and anaemia. Around 95% of dialysis patients were receiving erythropoietin and 47% intravenous iron. It is speculated that raising the target Hb for this population to 13 g/dl could shift the whole distribution curve to the left, reducing the proportion with anaemia. Doing this would require careful monitoring to steepen the distribution curve and limit the upper tail if complications of high haematocrits are to be avoided. PMID- 17724048 TI - International comparison of UK registry data (chapter 17). AB - In 2005, the incidence of renal replacement therapy (RRT) in the United Kingdom was 110 per million of the population (pmp) using the day 0 definition and 103 pmp using the day 90 definition. Relative to the 42 countries reporting data to the USRDS, the day 0 and day 90 rates for RRT incidence in the UK are the 32nd and 35th lowest, respectively. However, the overall incidence for the UK masks higher rates in Scotland, Wales and Northern Ireland (123, 129 and 140 pmp, respectively). Of the six countries with RRT incidence rates comparable with those in the UK (Australia, Finland, Malaysia, New Zealand, Norway and the Netherlands) three had relatively high rates for the age band 20-44, and two had relatively high rates for the age band 45-60. The proportion of incident patients with diabetes as the cause of established renal failure also varied considerably among these six comparator countries from 16% to 40% but rates of peritoneal dialysis utilization were comparable with that in the UK and generally higher than in countries with higher rates of RRT incidence. When transplantation rates were considered alongside prevalence rates for RRT, the UK position appeared relatively high at 46% (11th out of 37 countries), although still considerably lower than in Norway and the Netherlands (72 and 54%, respectively). Although variation in RRT incidence rate exists within the four countries of the UK, the overall RRT incidence, reported for the first time this year, appears similar to that observed in a number of demographically similar countries around the world. Examining the UK alongside the six comparator countries, different patterns of RRT incidence were observed across the age bands and variation in the RRT incidence secondary to diabetes mellitus raised interesting questions. The higher rates of renal transplantation achieved in several of the comparator countries also justifies further analysis. PMID- 17724050 TI - Introduction to the 2006 UK Renal Registry report (chapter 2). AB - The UK Renal Registry is part of the UK Renal Association and provides independent audit and analysis of renal replacement therapy in the UK. The Registry is funded directly by participating renal units through an annual fee per patient registered. The Registry is now collecting data on incidence and prevalence from 100% of UK renal units, with the five remaining non-linked sites in England providing summary data. Maintaining and enhancing Registry functionality will be an important touchstone for the Connecting for Health initiative. Collaboration with other formal agencies also promises an exciting prospect for future development. After a long proving period, the means, methods and roles have come together to complete an effective adjunct to clinical activity, planning, research and the performance of the renal community. PMID- 17724052 TI - Comorbidities in UK patients at the start of renal replacement therapy (chapter 6). AB - Comorbidity returns have continued to improve, albeit slowly, with centres running Mediqal software having the highest rates of completeness. Diabetes as a primary renal diagnosis accounted for 20% of those starting RRT, but a further 7% had diabetes present as a comorbid condition. The incidence of smoking remained high at 17% of diabetic patients, which was similar to that found in non diabetics. Twelve percent of the patients starting RRT had a previous myocardial infarction (MI) and 31% of those aged over 65 years starting RRT had ischaemic heart disease (IHD). Patients starting on peritoneal dialysis (PD) were on average 9 years younger than those on haemodialysis (HD) and had fewer comorbidities present. Patients starting RRT without any comorbidity present had a lower median estimated glomerular filtration rate (eGFR) than those with comorbid conditions. Patients with a previous MI or coronary artery bypass grafting (CABG), started RRT with slightly higher mean haemoglobin than those without comorbid conditions or other comorbid conditions. On univariate survival analysis, diabetes was not associated with an increased risk of death amongst patients aged over 65 years, possibly due to its close association with other comorbidities in this age group. In the multivariate survival analysis, the presence of ischaemic/neuropathic ulcers was the predictor of worst survival, followed by malignancy, previous MI and age per 10 year increment. Smoking was less common in both South Asian and black patients than whites (7 vs 17%) starting RRT. Twenty-three percent of both South Asian and white patients started RRT with IHD compared with only 12% of Black patients. PMID- 17724051 TI - All patients receiving renal replacement therapy in the United Kingdom in 2005 (chapter 4). AB - Summary data are provided for the whole United Kingdom. There were 41,776 adult patients alive on renal replacement therapy (RRT) in the UK at the end of 2005, a prevalence for adults of 694 pmp. Addition of 748 children under the age of 18 on RRT gives a total prevalence of 706 pmp. The more detailed analysis includes data on 37,534 patients from 65 of the 70 units which returned detailed data to the Registry: all in Northern Ireland, Scotland and Wales, and 45 of the 50 units in England. The annual increase in prevalence in the 38 renal units participating in the Registry since 2000 was 5.0%. There is substantial variation in the crude Local Authority area prevalence from 299 pmp to 1275 pmp. In general, areas with large ethnic minority populations had high standardized prevalence ratios (SPR). Nevertheless several Local Authority areas in South Wales (Methyr Tydfil, Swansea and Rhondda/Cynon/Taff) had a higher SPR than would be predicted from the local ethnic mix. Another group in North West England (Bury, Rochdale, Oldham and Salford), had a lower SPR than expected from the local ethnic mix. The median age of prevalent patients on RRT was 56.6 years, that of patients on HD 64.5 years, PD 59.2 years and transplanted patients 49.7 years. The median vintage of the whole RRT population was 5.1 years: that of transplanted patients was 9.8 years, HD patients 2.8 years and PD patients 2.1 years. The maximal prevalence rate (SPR) occurred in men (2270 pmp) in the 75-79-year age band and women (1144 pmp) in the 65-74-year age band. Of RRT patients in the UK, 45% had a transplant, 41.7% were on centre-based haemodialysis and 12% on peritoneal dialysis. The proportion of patients on home haemodialysis remained very small (1.2%) in spite of the recent NICE guidelines. The haemodialysis population is continuing to expand, mainly through growth in the proportion of patients undergoing dialysis in satellite units. The peritoneal dialysis population is continuing to contract in spite of the small but progressive rise in automated PD. The most common identifiable diagnosis in those under 65 was glomerulonephritis (18.0%) and in those over 65 it was diabetes (13.4%). One-year survival rates of prevalent patients in the different centres contributing to the UK Renal Registry are presented. The centres agreed to remove anonymity. There is no evidence of any significant differences in survival of prevalent patients between UK centres. The one-year survival of prevalent dialysis patients increased significantly from 1998 to 2004 in England (83.3% to 87.1% P = 0.0001 for linear trend), Scotland (84.0% to 87.0% P = 0.023 for linear trend) and Wales (83.4% to 86.1% P = 0.027 for linear trend). The test for non-linearity in this trend (indicating that there has been a large increase which is now tailing off) was significant for England and Wales. PMID- 17724053 TI - Haemodialysis dose and serum bicarbonate (chapter 7). AB - Data from 21 renal units was insufficient to allow analyses of the dose of dialysis in those units. Amongst the remainder, there is evidence of a progressive increase in the proportion of patients meeting the Renal Association audit standard for urea reduction ratio (URR). In the UK as a whole, 81% of prevalent haemodialysis patients met the standard for URR in 2005. Greater achievement of the standard in a given unit is associated with a higher median URR in that unit, although there is some evidence that some units have been able to narrow the distribution of achieved URR values. Achievement of the standard remains, as in previous years' Reports, less common amongst patients recently established on haemodialysis compared with those established on haemodialysis for longer. Correction of acidosis, as measured by serum bicarbonate concentration remains highly variable, although there is continued uncertainty about the interpretation of routine measurements of venous serum bicarbonate concentration in haemodialysis patients. Overall, approximately 64% of UK haemodialysis patients, and 50% of peritoneal dialysis patients met the Renal Association standard for serum bicarbonate in 2005. PMID- 17724054 TI - Management of anaemia in haemodialysis and peritoneal dialysis patients (chapter 8). AB - Forty-one percent of UK patients commence RRT with an Hb < 10.0 g/dl. The mean Hb at commencement of RRT is 10.3 g/dl. Eighty-five percent of patients on dialysis in the UK have an Hb > or = 10.0 g/dl by 6 months after commencement of RRT. The median Hb on haemodialysis in the UK is 11.8 g/dl with an IQR of 10.7-12.8 g/dl. Eighty-six percent of haemodialysis patients in the UK have a Hb > or = 10.0 g/dl. The median Hb on peritoneal dialysis in the UK is 12.0 g/dl with an IQR of 11.0-12.9 g/dl. Ninety percent of peritoneal dialysis patients in the UK have an Hb > or = 10.0 g/dl. In the UK, 49% of patients on PD and 48% of patients on haemodialysis have an Hb between 10.5-12.5 g/dl. The median ferritin in UK haemodialysis patients is 413 microg/l (IQR 262-623), 95% of UK haemodialysis patients have a ferritin > or =100 microg/l. The median ferritin in UK PD patients is 256 microg/l (IQR 147-421), 86% of UK peritoneal dialysis patients have a ferritin > or = 100 microg/l. A higher proportion of HD patients than PD patients receive ESA therapy (88% vs 76%). The ESA dose is higher for HD than PD patients (9204 vs 6080 IU/week). PMID- 17724056 TI - Nailing down PKC isoform specificity in diabetic nephropathy two's company, three's a crowd. PMID- 17724057 TI - Spirituality, quality of life and the dialysis patient. PMID- 17724059 TI - Clinical research of kidney diseases 1: researchable questions and valid answers. PMID- 17724060 TI - Identification of compositionally distinct regions in genomes using the centroid method. AB - MOTIVATION: It is known that most genomic regions of special interest, e.g. horizontally acquired sequences, genomic islands, etc. have distinct word (m-mer) compositions. Most of the earlier work along this direction, addressed di- and tri-nucleotide compositions. We present an approach that can be applied to analyze compositions of any given word size. The method, called the centroid approach, can reveal compositionally distinct regions in genomic sequences for any given word size. RESULTS: We applied our method to 50 bacterial genomes and demonstrated its ability to identify embedded sequences of varying lengths from distantly related organisms. We also investigated the genetic makeup of the regions identified as compositionally distinct by our method, for four organisms from our dataset. Pathogenicity island (PAI) components and genes encoding strain specific proteins are all frequently seen to be constituents of these regions. AVAILABILITY: Program is available on request from the authors. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 17724061 TI - Exploring the functional landscape of gene expression: directed search of large microarray compendia. AB - MOTIVATION: The increasing availability of gene expression microarray technology has resulted in the publication of thousands of microarray gene expression datasets investigating various biological conditions. This vast repository is still underutilized due to the lack of methods for fast, accurate exploration of the entire compendium. RESULTS: We have collected Saccharomyces cerevisiae gene expression microarray data containing roughly 2400 experimental conditions. We analyzed the functional coverage of this collection and we designed a context sensitive search algorithm for rapid exploration of the compendium. A researcher using our system provides a small set of query genes to establish a biological search context; based on this query, we weight each dataset's relevance to the context, and within these weighted datasets we identify additional genes that are co-expressed with the query set. Our method exhibits an average increase in accuracy of 273% compared to previous mega-clustering approaches when recapitulating known biology. Further, we find that our search paradigm identifies novel biological predictions that can be verified through further experimentation. Our methodology provides the ability for biological researchers to explore the totality of existing microarray data in a manner useful for drawing conclusions and formulating hypotheses, which we believe is invaluable for the research community. AVAILABILITY: Our query-driven search engine, called SPELL, is available at http://function.princeton.edu/SPELL. SUPPLEMENTARY INFORMATION: Several additional data files, figures and discussions are available at http://function.princeton.edu/SPELL/supplement. PMID- 17724062 TI - TMpro web server and web service: transmembrane helix prediction through amino acid property analysis. AB - TMpro is a transmembrane (TM) helix prediction algorithm that uses language processing methodology for TM segment identification. It is primarily based on the analysis of statistical distributions of properties of amino acids in transmembrane segments. This article describes the availability of TMpro on the internet via a web interface. The key features of the interface are: (i) output is generated in multiple formats including a user-interactive graphical chart which allows comparison of TMpro predicted segment locations with other labeled segments input by the user, such as predictions from other methods. (ii) Up to 5000 sequences can be submitted at a time for prediction. (iii) TMpro is available as a web server and is published as a web service so that the method can be accessed by users as well as other services depending on the need for data integration. AVAILABILITY: http://linzer.blm.cs.cmu.edu/tmpro/ (web server and help), http://blm.sis.pitt.edu:8080/axis/services/TMProFetcherService (web service). PMID- 17724063 TI - Current progress in bioinformatics 2007. PMID- 17724064 TI - Use of isolated hepatocyte preparations for cytochrome P450 inhibition studies: comparison with microsomes for Ki determination. AB - Predicting drug-drug interactions requires an assessment of the drug concentration available to the enzyme active site, both in vivo, and within an in vitro incubation. These predictions are confounded when the inhibitor accumulates within the liver, either as a result of active transport processes or intracellular binding (including lysosomal trapping). In theory, hepatocytes should provide a more accurate estimation of inhibitory potency compared with microsomes for those compounds that undergo hepatic accumulation. However, they are not routinely used for Ki determination and there is limited comparative information available. Therefore, the aims of this study were to compare Ki values determined in rat microsomes and freshly isolated hepatocytes using six cytochrome P450 inhibitors (miconazole, fluconazole, ketoconazole, quinine, fluoxetine, and fluvoxamine) with a range of uptake properties (cell-to-medium concentration ratios 4.2-6000). Inhibition studies were performed using four probe substrates for CYP2C, CYP2D, and CYP3A enzymes (tolbutamide and phenytoin, dextromethorphan and midazolam, respectively). Comparison of unbound Ki values (range 0.05-30 microM) showed good agreement between microsomes and hepatocytes for inhibition of 18 pathways of metabolism. In addition to this, there was no relationship between the cell-to-medium concentration ratios (covering over 3 orders of magnitude) and the microsomal to hepatocyte Ki ratio of these inhibitors. These data suggest that the hepatic accumulation of these inhibitors results from intracellular binding rather than the involvement of uptake transporters and indicate that microsomes and hepatocytes appear to be equivalent for determining the inhibitory potency of the six inhibitors investigated in the present study. PMID- 17724065 TI - The CYP3A4*18 allele, the most frequent coding variant in asian populations, does not significantly affect the midazolam disposition in heterozygous individuals. AB - The objective of this study was to identify CYP3A4 variants in Koreans and to characterize their functional consequences in vitro and in vivo. Four single nucleotide polymorphisms were identified in 50 Koreans by direct DNA sequencing. In an additional genotyping using 248 subjects, CYP3A4(*)18 was confirmed as the most frequent coding variant in Koreans at 1.7%, and its frequency was similar to that of Asians, suggesting that CYP3A4(*)18 would be the highest coding variant in Asians. The recombinant CYP3A4.18 protein prepared in baculovirus expression system showed 67.4% lower Vmax and 1.8-fold higher K(m) for midazolam 1' hydroxylation compared with the wild type. The mean values of Cmax and area under the concentration curve (AUC) in the CYP3A4(*)1/(*)18 and CYP3A5(*)1/(*)3 subjects (n = 8) were 63% and 32% higher than in CYP3A4(*)1/(*)1 and CYP3A5(*)1/(*)3 carriers (n = 8), respectively. Although the in vitro assay exhibited a significant reduction of the enzyme activity for midazolam, the in vivo differences associated with the CYP3A4(*)1/(*)18 tend to be low (P < 0.07 in Cmax and P < 0.09 in AUC). In summary, the heterozygous CYP3A4(*)1/(*)18 does not appear to cause a significant change of midazolam disposition in vivo; however, the clinical relevance of CYP3A4(*)18/(*)18 remains to be evaluated. PMID- 17724066 TI - Anthrax protective antigen cleavage and clearance from the blood of mice and rats. AB - Bacillus anthracis protective antigen (PA) is an 83-kDa (PA83) protein that is cleaved to the 63-kDa protein (PA63) as an essential step in binding and internalizing lethal factor (LF). To assess in vivo receptor saturating PA concentrations, we injected mice with PA variants and measured the PA remaining in the blood at various times using PA83- and PA63-specific enzyme-linked immunosorbent assays. We found that both wild-type PA (WT-PA) and a receptor binding-defective mutant (Ub-PA) were cleaved to PA63 independent of their ability to bind cells. This suggested a PA-acting protease activity in the blood. The protease cleaved PA at the furin cleavage sequence because furin site modified PA mutants were not cleaved. Cleavage measured in vitro was leupeptin sensitive and dependent on calcium. Cell surface cleavage was important for toxin clearance, however, as Ub-PA and uncleavable PA mutants were cleared at slower rates than WT-PA. The cell binding-independent cleavage of PA was also verified by using Ub-PA (which is still cleaved) to rescue mice from toxin challenge by competitively binding circulating LF. This mutant was able to rescue mice even when given 12 h before toxin challenge. Its therapeutic ability was comparable to that of dominant-negative PA, which binds cells but does not allow LF translocation, and to the protection afforded through receptor clearance by WT-PA and uncleavable receptor binding-competent mutants. The PA cleavage and clearance observed in mice did not appear to have a role in the differential mouse susceptibility as it occurred similarly in lethal toxin (LT)-resistant DBA/2J and LT-sensitive BALB/cJ mice. Interestingly, PA63 was not found in LT-resistant or sensitive rats and PA83 clearance was slower in rats than in mice. Finally, to determine the minimum amount of PA required in circulation for LT toxicity in mice, we administered time-separated injections of PA and LF and showed that lethality of LF for mice after PA was no longer measurable in circulation, suggesting active PA sequestration at tissue surfaces. PMID- 17724067 TI - Construction and characterization of single-chain variable fragment antibodies directed against the Bordetella pertussis surface adhesins filamentous hemagglutinin and pertactin. AB - A single-chain variable fragment (scFv) antibody library against Bordetella pertussis was constructed using M13 phage display. The library was enriched for phages surface displaying functional scFv by biopanning against B. pertussis immobilized on polystyrene plates. Two hundred eighty-eight individual clones from the enriched library were screened for binding to B. pertussis cells, filamentous hemagglutinin (FHA), and pertactin (PRN) in enzyme-linked immunosorbent assays (ELISAs). Based on the binding ability, the clones were put into eight groups. The scFv DNA inserts from the 288 clones were digested with BstOI, and 18 unique restriction patterns, named types 1 to 18, were found. Eight clones (types 1 to 7 and 18) were selected for further testing against FHA, PRN, and B. pertussis by ELISA. The results showed that types 1, 5, 7, and 18 bound strongly to B. pertussis cells as well as FHA and PRN. Type 3 bound strongly to the cells and FHA but weakly to PRN. Types 4 and 6 bound FHA only, and type 2 did not bind to the cells or antigens. The ability of the eight clones to inhibit B. pertussis from binding to HEp-2 cells was assayed. Types 1, 5, and 7, but not the remaining clones, inhibited the adherence of B. pertussis to HEp-2 cells. The scFvs were sequenced, and the deduced amino acid sequence showed that the scFvs were different antibodies. Maltose-binding protein (MBP) fusion proteins composed of three different regions of FHA (heparin-binding domain, carbohydrate recognition domain, and the RGD triplet motif) were constructed. The three fusion proteins and Mal85 (MBP-FHA type I domain) were used to map the binding sites for scFvs of types 1, 5, and 7 by ELISA. The results showed that all three scFvs bound to the heparin-binding domain fusion protein but not the other fusion proteins. BALB/c mice who received recombinant phage-treated B. pertussis had reduced bacterial counts in the nasal cavity, trachea, and lungs compared to the control groups. PMID- 17724068 TI - Modulation of host innate immune response in the bladder by uropathogenic Escherichia coli. AB - Uropathogenic Escherichia coli (UPEC), the most frequent cause of urinary tract infection (UTI), is associated with an inflammatory response which includes the induction of cytokine/chemokine secretion by urothelial cells and neutrophil recruitment to the bladder. Recent studies indicate, however, that UPEC can evade the early activation of urothelial innate immune response in vitro. In this study, we report that infection with the prototypic UPEC strain NU14 suppresses tumor necrosis factor alpha (TNF-alpha)-mediated interleukin-8 (CXCL-8) and interleukin-6 (CXCL-6) secretion from urothelial cell cultures compared to infection with a type 1 piliated E. coli K-12 strain. Furthermore, examination of a panel of clinical E. coli isolates revealed that 15 of 17 strains also possessed the ability to suppress cytokine secretion. In a murine model of UTI, NU14 infection resulted in diminished levels of mRNAs encoding keratinocyte derived chemokine, macrophage inflammatory peptide 2, and CXCL-6 in the bladder relative to infection with an E. coli K-12 strain. Furthermore, reduced stimulation of inflammatory chemokine production during NU14 infection correlated with decreased levels of bladder and urine myeloperoxidase and increased bacterial colonization. These data indicate that a broad phylogenetic range of clinical E. coli isolates, including UPEC, may evade the activation of innate immune response in the urinary tract, thereby providing a pathogenic advantage. PMID- 17724069 TI - Helicobacter pylori induces CCL20 expression. AB - CCL20 attracts immature dendritic cells and memory T cells and plays a role on mucosal surfaces in inflammation. However, whether Helicobacter pylori infection induces CCL20 in human gastric epithelial cells remains to be determined. The aim of this study was to analyze the molecular mechanism of H. pylori-induced CCL20 expression. Expression of CCL20 mRNA was assessed by reverse transcription-PCR. Five normal and five H. pylori-infected gastric tissue samples were stained immunohistochemically for CCL20. A luciferase assay was used to monitor activation of the CCL20 gene promoter, and an electrophoretic mobility shift assay was used to explore the binding of transcription factors to this promoter. The CCL20 expression in epithelial cells of H. pylori-positive tissues was higher than that in H. pylori-negative tissues. H. pylori induced CCL20 expression in gastric epithelial cell lines, and the induction was dependent on an intact cag pathogenicity island. Activation of the CCL20 promoter by H. pylori occurred through the action of NF-kappaB. Transfection of IkappaB kinase and NF-kappaB inducing kinase dominant negative mutants inhibited H. pylori-mediated activation of CCL20. Treatment with an inhibitor of Hsp90 suppressed H. pylori-induced CCL20 mRNA due to deactivation of NF-kappaB. Collectively, these results suggest that H. pylori activates NF-kappaB through an intracellular signaling pathway that involves IkappaB kinase and NF-kappaB-inducing kinase, leading to CCL20 gene transcription, and that Hsp90 is a crucial regulator of H. pylori-induced CCL20 expression, presumably contributing to the immune response in H. pylori. PMID- 17724071 TI - Severe tryptophan starvation blocks onset of conventional persistence and reduces reactivation of Chlamydia trachomatis. AB - The intracellular survival of the bacterial pathogen Chlamydia trachomatis depends on protein synthesis by the microbe soon after internalization. Pharmacologic inhibition of bacterial translation inhibits early trafficking of the parasitophorous vacuole (inclusion) to the microtubule-organizing center (MTOC) and promotes its fusion with lysosomes, which is normally blocked by Chlamydia. Depletion of cellular tryptophan pools by gamma interferon-inducible indoleamine-2,3-dioxygenase (IDO) is believed to be the major innate immune mechanism controlling C. trachomatis infection in human cells, an action to which the bacteria can respond by converting into a nonreplicating but highly reactivatable persistent state. However, whether severe IDO-mediated tryptophan starvation can be sufficient to fully arrest the chlamydial life cycle and thereby counteract the onset of persistence is unknown. Here we demonstrate that at low exogenous tryptophan concentrations a substantial fraction of C. trachomatis bacteria fail to traffic to the MTOC or to switch into the conventional persistent state in gamma interferon-induced human cells. The organisms stay scattered in the cell periphery, do not retain infectivity, and display only low transcriptional activity. Importantly, the rate at which these aberrant Chlamydia bacteria become reactivated upon replenishment of cellular tryptophan pools is substantially lower. Thus, severe tryptophan depletion in cells with high IDO activity affects chlamydial development more rigorously than previously described. PMID- 17724070 TI - In vivo evidence of Pseudomonas aeruginosa nutrient acquisition and pathogenesis in the lungs of cystic fibrosis patients. AB - One of the hallmarks of Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients is very-high-cell-density (HCD) replication in the lung, allowing this bacterium to induce virulence controlled by the quorum-sensing systems. However, the nutrient sources sustaining HCD replication in this chronic infection are largely unknown. Here, we performed microarray studies of P. aeruginosa directly isolated from the lungs of CF patients to demonstrate its metabolic capability and virulence in vivo. In vivo microarray data, confirmed by real-time reverse transcription-PCR, indicated that the P. aeruginosa population expressed several genes for virulence, drug resistance, and utilization of multiple nutrient sources (lung surfactant lipids and amino acids) contributing to HCD replication. The most abundant lung surfactant lipid molecule, phosphatidylcholine (PC), induces key genes of P. aeruginosa pertinent to PC degradation in vitro as well as in vivo within the lungs of CF patients. The results support recent research indicating that P. aeruginosa exists in the lungs of CF patients as a diverse population with full virulence potential. The data also indicate that there is deregulation of several pathways, suggesting that there is in vivo evolution by deregulation of a large portion of the transcriptome during chronic infection in CF patients. To our knowledge, this is the first in vivo transcriptome analysis of P. aeruginosa in a natural infection in CF patients, and the results indicate several important aspects of P. aeruginosa pathogenesis, drug resistance, nutrient utilization, and general metabolism within the lungs of CF patients. PMID- 17724072 TI - Systemic translocation of Salmonella enterica serovar Dublin in cattle occurs predominantly via efferent lymphatics in a cell-free niche and requires type III secretion system 1 (T3SS-1) but not T3SS-2. AB - Salmonella enterica is an important diarrheal pathogen, and infections may involve severe systemic sequelae depending on serovar- and host-specific factors. The molecular mechanisms underlying translocation of host-restricted and specific serovars of S. enterica from the intestines to distal organs are ill defined. By surgical cannulation of lymph and blood vessels draining the distal ileum in cattle, S. enterica serovar Dublin was observed to translocate predominantly via mesenteric lymph nodes to efferent lymphatics in a manner that correlates with systemic virulence, since the fowl typhoid-associated serovar Gallinarum translocated at a significantly lower level. While both S. enterica serovars Dublin and Gallinarum were intracellular while in the intestinal mucosa and associated with major histocompatibility complex class II-positive cells, the bacteria were predominantly extracellular within efferent lymph. Screening of a library of signature-tagged serovar Dublin mutants following oral inoculation of calves defined the role of 36 virulence-associated loci in enteric and systemic phases of infection. The number and proportion of tagged clones reaching the liver and spleen early after oral infection were identical to the values in efferent lymph, implying that this may be a relevant mode of dissemination. Coinfection studies confirmed that lymphatic translocation requires the function of type III secretion system 1 (T3SS-1) but, remarkably, not T3SS-2. This is the first description of the mode and genetics of systemic translocation of serovar Dublin in its natural host. PMID- 17724073 TI - Antigen-specific cellular and humoral responses are induced by intradermal Mycobacterium leprae infection of the mouse ear. AB - Leprosy is caused by infection with Mycobacterium leprae. The immune response of leprosy patients can be highly diverse, ranging from strong cellular responses accompanied by an apparent deficit of M. leprae-specific antibodies to strong humoral responses with a deficit of cell-mediated responses. Leprosy takes many years to manifest, and this has precluded analyses of disease and immune response development in infected humans. In an attempt to better define development of the immune response during leprosy we have developed an M. leprae ear infection model. Intradermal inoculation of M. leprae into the ear supported not only infection but also the development of a chronic inflammatory response. The inflammatory response was localized, comprising a T-cell infiltration into the ear and congestion of cells in the draining lymph nodes. The development of local chronic inflammation was prevented by rifampin treatment. Importantly, and in contrast to subcutaneous M. leprae footpad infection, systemic M. leprae-specific gamma interferon and antibody responses were detected following intradermal ear infection. These results indicate the utility of intradermal ear infection for both induction and understanding of the immune response during M. leprae infection and the identification or testing of new leprosy treatments. PMID- 17724074 TI - Impact of alcaligin siderophore utilization on in vivo growth of Bordetella pertussis. AB - Bordetella pertussis, the causative agent of human whooping cough, or pertussis, is an obligate human pathogen with diverse high-affinity transport systems for the assimilation of iron, a biometal that is essential for growth. Under iron starvation stress conditions, B. pertussis produces the siderophore alcaligin. The alcaligin siderophore gene cluster, consisting of the alcABCDERS and fauA genes, encodes activities required for alcaligin biosynthesis, the export of the siderophore from the cell, the uptake of the ferric alcaligin complex across the outer membrane, and the transcriptional activation of alcaligin system genes by an autogenous mechanism involving alcaligin sensing. The fauA gene encodes a 79 kDa TonB-dependent outer membrane receptor protein required for the uptake and utilization of ferric alcaligin as an iron source. In this study, using mixed infection competition experiments in a mouse respiratory model, inactivation of the B. pertussis ferric alcaligin receptor protein was found to have a profound impact on in vivo growth and survival of a fauA mutant compared with a coinfecting wild-type strain. The attenuating effect of fauA inactivation was evident early in the course of the infection, suggesting that the contribution of ferric alcaligin transport to the ecological fitness of B. pertussis may be important for adaptation to iron-restricted host conditions that exist at the initial stages of infection. Alcaligin-mediated iron acquisition by B. pertussis may be critical for successful host colonization and establishment of infection. PMID- 17724076 TI - Identification of LpxL, a late acyltransferase of Francisella tularensis. AB - Lipopolysaccharide (LPS) is a major component of the outer membrane of gram negative bacteria, and the lipid A region of LPS mediates stimulation of the immune system in a structure-dependent manner. Unlike the LPS of many other gram negative bacteria, the LPS of Francisella tularensis isolated from in vitro cultures is not proinflammatory. This observed lack of proinflammatory prowess may reflect structural features of the lipid A, such as the number and length of the acyl chains and the single-phosphate group. To better understand this phenotype, we have begun to elucidate LPS biosynthesis in F. tularensis. We present complementation, mutational, and chemical data demonstrating that F. tularensis FTT0232c encodes a functional late acyltransferase enzyme with specificity similar to that of the Escherichia coli LpxL ortholog. Expression of this late acyltransferase complemented the temperature-sensitive and hypoacylated lipid A phenotypes of an E. coli lpxL mutant, expression of FTT0232c is increased during intracellular growth relative to that during in vitro growth, and finally, LPS obtained from a mutant of F. tularensis lacking FTT0232c showed an abundant triacyl lipid A species after mass spectrometric analysis, consistent with the loss of an LpxL late acyltransferase. PMID- 17724075 TI - Effects of DNA- and Mycobacterium bovis BCG-based delivery of the Flt3 ligand on protective immunity to Mycobacterium tuberculosis. AB - The control of intracellular pathogens such as Mycobacterium tuberculosis is dependent on the activation and maintenance of pathogen-reactive T cells. Dendritic cells (DCs) are the major antigen-presenting cells initiating antimycobacterial T-cell responses in vivo. To investigate if immunization strategies that aim to optimize DC function can improve protective immunity against virulent mycobacterial infection, we exploited the ability of the hematopoietic growth factor Fms-like tyrosine kinase 3 ligand (Flt3L) to expand the number of DCs in vivo. A DNA fusion of the genes encoding murine Flt3L and M. tuberculosis antigen 85B stimulated enhanced gamma interferon (IFN-gamma) release by T cells and provided better protection against virulent M. tuberculosis than DNA encoding the single components. Vaccination of mice with a recombinant Mycobacterium bovis BCG strain secreting Flt3L (BCG:Flt3L) led to early expansion of DCs compared to immunization with BCG alone, and this effect was associated with increased stimulation of BCG-reactive IFN-gamma-secreting T cells. BCG and BCG:Flt3L provided similar protective efficacies against low-dose aerosol M. tuberculosis; however, immunization of immunodeficient mice revealed that BCG:Flt3L was markedly less virulent than conventional BCG. These results demonstrate the potential of in vivo targeting of DCs to improve antimycobacterial vaccine efficacy. PMID- 17724078 TI - Break-induced loss of heterozygosity in fission yeast: dual roles for homologous recombination in promoting translocations and preventing de novo telomere addition. AB - Loss of heterozygosity (LOH), a causal event in tumorigenesis, frequently encompasses multiple genetic loci and whole chromosome arms. However, the mechanisms leading to such extensive LOH are poorly understood. We investigated the mechanisms of DNA double-strand break (DSB)-induced extensive LOH by screening for auxotrophic marker loss approximately 25 kb distal to an HO endonuclease break site within a nonessential minichromosome in Schizosaccharomyces pombe. Extensive break-induced LOH was infrequent, resulting from large translocations through both allelic crossovers and break-induced replication. These events required the homologous recombination (HR) genes rad32(+), rad50(+), nbs1(+), rhp51(+), rad22(+), rhp55(+), rhp54(+), and mus81(+). Surprisingly, LOH was still observed in HR mutants, which resulted predominantly from de novo telomere addition at the break site. De novo telomere addition was most frequently observed in rad22Delta and rhp55Delta backgrounds, which disrupt HR following end resection. Further, levels of de novo telomere addition, while increased in ku70Delta rhp55Delta strains, were reduced in exo1Delta rhp55Delta and an rhp55Delta strain overexpressing rhp51. These findings support a model in which HR prevents de novo telomere addition at DSBs by competing for resected ends. Together, these results suggest that the mechanisms of break-induced LOH may be predicted from the functional status of the HR machinery. PMID- 17724077 TI - G protein-coupled receptor Ca2+-linked mitochondrial reactive oxygen species are essential for endothelial/leukocyte adherence. AB - Receptor-mediated signaling is commonly associated with multiple functions, including the production of reactive oxygen species. However, whether mitochondrion-derived superoxide (mROS) contributes directly to physiological signaling is controversial. Here we demonstrate a previously unknown mechanism in which physiologic Ca(2+)-evoked mROS production plays a pivotal role in endothelial cell (EC) activation and leukocyte firm adhesion. G protein-coupled receptor (GPCR) and tyrosine kinase-mediated inositol 1,4,5-trisphosphate dependent mitochondrial Ca(2+) uptake resulted in NADPH oxidase-independent mROS production. However, GPCR-linked mROS production did not alter mitochondrial function or trigger cell death but rather contributed to activation of NF-kappaB and leukocyte adhesion via the EC induction of intercellular adhesion molecule 1. Dismutation of mROS by manganese superoxide dismutase overexpression and a cell permeative superoxide dismutase mimetic ablated NF-kappaB transcriptional activity and facilitated leukocyte detachment from the endothelium under simulated circulation following GPCR- but not cytokine-induced activation. These results demonstrate that mROS is the downstream effector molecule that translates receptor-mediated Ca(2+) signals into proinflammatory signaling and leukocyte/EC firm adhesion. PMID- 17724079 TI - Inhibition of mammalian target of rapamycin induces phosphatidylinositol 3-kinase dependent and Mnk-mediated eukaryotic translation initiation factor 4E phosphorylation. AB - The initiation factor eukaryotic translation initiation factor 4E (eIF4E) plays a critical role in initiating translation of mRNAs, including those encoding oncogenic proteins. Therefore, eIF4E is considered a survival protein involved in cell cycle progression, cell transformation, and apoptotic resistance. Phosphorylation of eIF4E (usually at Ser209) increases its binding affinity for the cap of mRNA and may also favor its entry into initiation complexes. Mammalian target of rapamycin (mTOR) inhibitors suppress cap-dependent translation through inhibition of the phosphorylation of eIF4E-binding protein 1. Paradoxically, we have shown that inhibition of mTOR signaling increases eIF4E phosphorylation in human cancer cells. In this study, we focused on revealing the mechanism by which mTOR inhibition increases eIF4E phosphorylation. Silencing of either mTOR or raptor could mimic mTOR inhibitors' effects to increase eIF4E phosphorylation. Moreover, knockdown of mTOR, but not rictor or p70S6K, abrogated rapamycin's ability to increase eIF4E phosphorylation. These results indicate that mTOR inhibitor-induced eIF4E phosphorylation is secondary to mTOR/raptor inhibition and independent of p70S6K. Importantly, mTOR inhibitors lost their ability to increase eIF4E phosphorylation only in cells where both Mnk1 and Mnk2 were knocked out, indicating that mTOR inhibitors increase eIF4E phosphorylation through a Mnk-dependent mechanism. Given that mTOR inhibitors failed to increase Mnk and eIF4E phosphorylation in phosphatidylinositol 3-kinase (PI3K)-deficient cells, we conclude that mTOR inhibition increases eIF4E phosphorylation through a PI3K-dependent and Mnk-mediated mechanism. In addition, we also suggest an effective therapeutic strategy for enhancing mTOR-targeted cancer therapy by cotargeting mTOR signaling and Mnk/eIF4E phosphorylation. PMID- 17724080 TI - Improved glucose homeostasis in mice with muscle-specific deletion of protein tyrosine phosphatase 1B. AB - Obesity and type 2 diabetes are characterized by insulin resistance. Mice lacking the protein-tyrosine phosphatase PTP1B in all tissues are hypersensitive to insulin but also have diminished fat stores. Because adiposity affects insulin sensitivity, the extent to which PTP1B directly regulates glucose homeostasis has been unclear. We report that mice lacking PTP1B only in muscle have body weight and adiposity comparable to those of controls on either chow or a high-fat diet (HFD). Muscle triglycerides and serum adipokines are also affected similarly by HFD in both groups. Nevertheless, muscle-specific PTP1B(-/-) mice exhibit increased muscle glucose uptake, improved systemic insulin sensitivity, and enhanced glucose tolerance. These findings correlate with and are most likely caused by increased phosphorylation of the insulin receptor and its downstream signaling components. Thus, muscle PTP1B plays a major role in regulating insulin action and glucose homeostasis, independent of adiposity. In addition, rosiglitazone treatment of HFD-fed control and muscle-specific PTP1B(-/-) mice revealed that rosiglitazone acts additively with PTP1B deletion. Therefore, combining PTP1B inhibition with thiazolidinediones should be more effective than either alone for treating insulin-resistant states. PMID- 17724081 TI - Thioredoxin and TRAF family proteins regulate reactive oxygen species-dependent activation of ASK1 through reciprocal modulation of the N-terminal homophilic interaction of ASK1. AB - Apoptosis signal-regulating kinase 1 (ASK1), a member of the mitogen-activated protein kinase kinase kinase family, plays pivotal roles in reactive oxygen species (ROS)-induced cellular responses. In resting cells, endogenous ASK1 constitutively forms a homo-oligomerized but still inactive high-molecular-mass complex including thioredoxin (Trx), which we designated the ASK1 signalosome. Upon ROS stimulation, the ASK1 signalosome unbinds from Trx and forms a fully activated higher-molecular-mass complex, in part by recruitment of tumor necrosis factor receptor-associated factor 2 (TRAF2) and TRAF6. However, the precise mechanisms by which Trx inhibits and TRAF2 and TRAF6 activate ASK1 have not been elucidated fully. Here we demonstrate that the N-terminal homophilic interaction of ASK1 through the N-terminal coiled-coil domain is required for ROS-dependent activation of ASK1. Trx inhibited this interaction of ASK1, which was, however, enhanced by expression of TRAF2 or TRAF6 or by treatment of cells with H2O2. Furthermore, the H2O2-induced interaction was reduced by double knockdown of TRAF2 and TRAF6. These findings demonstrate that Trx, TRAF2, and TRAF6 regulate ASK1 activity by modulating N-terminal homophilic interaction of ASK1. PMID- 17724082 TI - Structural changes in Mcm5 protein bypass Cdc7-Dbf4 function and reduce replication origin efficiency in Saccharomyces cerevisiae. AB - Eukaryotic chromosomal replication is a complicated process with many origins firing at different efficiencies and times during S phase. Prereplication complexes are assembled on all origins in G(1) phase, and yet only a subset of complexes is activated during S phase by DDK (for Dbf4-dependent kinase) (Cdc7 Dbf4). The yeast mcm5-bob1 (P83L) mutation bypasses DDK but results in reduced intrinsic firing efficiency at 11 endogenous origins and at origins located on minichromosomes. Origin efficiency may result from Mcm5 protein assuming an altered conformation, as predicted from the atomic structure of an archaeal MCM (for minichromosome maintenance) homologue. Similarly, an intragenic mutation in a residue predicted to interact with P83L suppresses the mcm5-bob1 bypass phenotype. We propose DDK phosphorylation of the MCM complex normally results in a single, highly active conformation of Mcm5, whereas the mcm5-bob1 mutation produces a number of conformations, only one of which is permissive for origin activation. Random adoption of these alternate states by the mcm5-bob1 protein can explain both how origin firing occurs independently of DDK and why origin efficiency is reduced. Because similar mutations in mcm2 and mcm4 cannot bypass DDK, Mcm5 protein may be a unique Mcm protein that is the final target of DDK regulation. PMID- 17724083 TI - Regulation of gene transcription by the histone H2A N-terminal domain. AB - Histone N-terminal domains play critical roles in regulating chromatin structure and gene transcription. Relatively little is known, however, about the role of the histone H2A N-terminal domain in transcription regulation. We have used DNA microarrays to characterize the changes in genome-wide expression caused by mutations in the N-terminal domain of histone H2A. Our results indicate that the N-terminal domain of histone H2A functions primarily to repress the transcription of a large subset of the Saccharomyces cerevisiae genome and that most of the H2A repressed genes are also repressed by the histone H2B N-terminal domain. Using the histone H2A microarray data, we selected three reporter genes (BNA1, BNA2, and GCY1), which we subsequently used to map regions in the H2A N-terminal domain responsible for this transcriptional repression. These studies revealed that a small subdomain in the H2A N-terminal tail, comprised of residues 16 to 20, is required for the transcriptional repression of these reporter genes. Deletion of either the entire histone H2A N-terminal domain or just this small subdomain imparts sensitivity to UV irradiation. Finally, we show that two residues in this H2A subdomain, serine-17 and arginine-18, are specifically required for the transcriptional repression of the BNA2 reporter gene. PMID- 17724084 TI - Conditional deletion of activating protein 2alpha (AP-2alpha) in the developing retina demonstrates non-cell-autonomous roles for AP-2alpha in optic cup development. AB - Activating protein 2alpha (AP-2alpha) is known to be expressed in the retina, and AP-2alpha-null mice exhibit defects in the developing optic cup, including patterning of the neural retina (NR) and a replacement of the dorsal retinal pigmented epithelium (RPE) with NR. In this study, we analyzed the temporal and spatial retinal expression patterns of AP-2alpha and created a conditional deletion of AP-2alpha in the developing retina. AP-2alpha exhibited a distinct expression pattern in the developing inner nuclear layer of the retina, and colocalization studies indicated that AP-2alpha was exclusively expressed in postmitotic amacrine cell populations. Targeted deletion of AP-2alpha in the developing retina did not result in observable retinal defects. Further examination of AP-2alpha-null mutants revealed that the severity of the RPE defect was variable and, although defects in retinal lamination occur at later embryonic stages, earlier stages showed normal lamination and expression of markers for amacrine and ganglion cells. Together, these data demonstrate that, whereas AP-2alpha alone does not play an intrinsic role in retinogenesis, it has non-cell-autonomous effects on optic cup development. Additional expression analyses showed that multiple AP-2 proteins are present in the developing retina, which will be important to future studies. PMID- 17724085 TI - The human F-Box DNA helicase FBH1 faces Saccharomyces cerevisiae Srs2 and postreplication repair pathway roles. AB - The Saccharomyces cerevisiae Srs2 UvrD DNA helicase controls genome integrity by preventing unscheduled recombination events. While Srs2 orthologues have been identified in prokaryotic and lower eukaryotic organisms, human orthologues of Srs2 have not been described so far. We found that the human F-box DNA helicase hFBH1 suppresses specific recombination defects of S. cerevisiae srs2 mutants, consistent with the finding that the helicase domain of hFBH1 is highly conserved with that of Srs2. Surprisingly, hFBH1 in the absence of SRS2 also suppresses the DNA damage sensitivity caused by inactivation of postreplication repair-dependent functions leading to PCNA ubiquitylation. The F-box domain of hFBH1, which is not present in Srs2, is crucial for hFBH1 functions in substituting for Srs2 and postreplication repair factors. Furthermore, our findings indicate that an intact F-box domain, acting as an SCF ubiquitin ligase, is required for the DNA damage induced degradation of hFBH1 itself. Overall, our findings suggest that the hFBH1 helicase is a functional human orthologue of budding yeast Srs2 that also possesses self-regulation properties necessary to execute its recombination functions. PMID- 17724086 TI - Essential role of endothelial Smad4 in vascular remodeling and integrity. AB - New blood vessels are formed through the assembly or sprouting of endothelial cells (ECs) and become stabilized by the formation of perivascular matrix and the association with supporting mural cells. To investigate the role of endothelial Smad4 in vascular development, we deleted the Smad4 gene specifically in ECs using the Cre-LoxP system. EC-specific Smad4 mutant mice died at embryonic day 10.5 due to cardiovascular defects, including attenuated vessels sprouting and remodeling, collapsed dorsal aortas, enlarged hearts with reduced trabeculae, and failed endocardial cushion formation. Noticeably, Smad4-deficient ECs demonstrated an intrinsic defect in tube formation in vitro. Furthermore, the mutant vascular ECs dissociated away from the surrounding cells and suffered from impaired development of vascular smooth muscle cells. The disturbed vascular integrity and maturation was associated with aberrant expression of angiopoietins and a gap junction component, connexin43. Collectively, we have provided direct functional evidence that Smad4 activity in the developing ECs is essential for blood vessel remodeling, maturation, and integrity. PMID- 17724089 TI - Activation of nuclear factor (erythroid-2 like) factor 2 by toxic bile acids provokes adaptive defense responses to enhance cell survival at the emergence of oxidative stress. AB - Oxidative stress, causing necrotic and apoptotic cell death, is associated with bile acid toxicity. Using liver (HepG2, Hepa1c1c7, and primary human hepatocytes) and intestinal (C2bbe1, a Caco-2 subclone) cells, we demonstrated that toxic bile acids, such as lithocholic acid (LCA) and chenodeoxycholic acid, induced the nuclear factor (erythroid-2 like) factor 2 (Nrf2) target genes, especially the rate-limiting enzyme in glutathione (GSH) biosynthesis [glutamate cysteine ligase modulatory subunit (GCLM) and glutamate cysteine ligase catalytic subunit (GCLC)] and thioredoxin reductase 1. Nrf2 activation and induction of Nrf2 target genes were also evident in vivo in the liver of CD-1 mice treated 7 to 8 h or 4 days with LCA. Silencing of Nrf2 via small-interfering RNA suppressed basal and bile acid-induced mRNA levels of the above-mentioned genes. Consistent with this, overexpression of Nrf2 enhanced, but dominant-negative Nrf2 attenuated, Nrf2 target gene induction by bile acids. The activation of Nrf2-antioxidant responsive element (ARE) transcription machinery by bile acids was confirmed by increased nuclear accumulation of Nrf2, enhanced ARE-reporter activity, and increased Nrf2 binding to ARE. It is noteworthy that Nrf2 silencing increased cell susceptibility to LCA toxicity, as evidenced by reduced cell viability and increased necrosis and apoptosis. Concomitant with GCLC/GCLM induction, cellular GSH was significantly increased in bile acid-treated cells. Cotreatment with N acetyl-l-cysteine, a GSH precursor, ameliorated LCA toxicity, whereas cotreatment with buthionine sulfoximine, a GSH synthesis blocker, exacerbated it. In summary, this study provides molecular evidence linking bile acid toxicity to oxidative stress. Nrf2 is centrally involved in counteracting such oxidative stress by enhancing adaptive antioxidative response, particularly GSH biosynthesis, and hence cell survival. PMID- 17724087 TI - DLGH1 is a negative regulator of T-lymphocyte proliferation. AB - Discs large homolog 1 (DLGH1), a founding member of the membrane-associated guanylate kinase family of proteins containing PostSynaptic Density-95/Discs large/Zona Occludens-1 domains, is an ortholog of the Drosophila tumor suppressor gene Discs large. In the mammalian embryo, DLGH1 is essential for normal urogenital morphogenesis and the development of skeletal and epithelial structures. Recent reports also indicate that DLGH1 may be a critical mediator of signals triggered by the antigen receptor complex in T lymphocytes by functioning as a scaffold coordinating the activities of T-cell receptor (TCR) signaling proteins at the immune synapse. However, it remains unclear if DLGH1 functions to enhance or attenuate signals emanating from the TCR. Here, we used Dlgh1 gene targeted mice to determine the requirement for DLGH1 in T-cell development and activation. Strikingly, while all major subsets of T cells appear to undergo normal thymic development in the absence of DLGH1, peripheral lymph node Dlgh1(-/ ) T cells show a hyper-proliferative response to TCR-induced stimulation. These data indicate that, consistent with the known function of Discs large proteins as tumor suppressors and attenuators of cell division, in T lymphocytes, DLGH1 functions as a negative regulator of TCR-induced proliferative responses. PMID- 17724088 TI - Ciprofloxacin prolonged-release tablets do not affect warfarin pharmacokinetics and pharmacodynamics. AB - The purpose of this study was to determine whether the pharmacokinetics of warfarin and ciprofloxacin PR (a prolonged-release formulation of ciprofloxacin) were altered after coadministration. Eighteen healthy male volunteers were given a single oral 7.5-mg dose of warfarin, a single oral 500-mg dose of ciprofloxacin PR, or both drugs administered together in a randomized, open-label, 3-way crossover study. Ciprofloxacin concentrations, warfarin (R)- and (S)-enantiomer concentrations, prothrombin time, and activated partial thromboplastin time were measured over 120 hours following study drug administration. There were no significant differences in pharmacokinetic or pharmacodynamic parameters among treatments. A slightly greater value of half-life for (R)-warfarin was observed when coadministered with ciprofloxacin PR compared with warfarin administered alone (52.6 vs 50.1 hours, P = .029). This difference is not considered clinically relevant, because the values remain similar. These results show that warfarin pharmacokinetics and pharmacodynamics are not altered with concomitant administration of ciprofloxacin PR. PMID- 17724090 TI - Combined proximal and distal realignment procedures to treat the habitual dislocation of the patella in adults. AB - BACKGROUND: Habitual dislocation of the patella (HDP) is a rare condition. Many surgical procedures using proximal realignment have been reported to treat HDP in children, with around 80% satisfactory results. However, few articles have addressed the treatment of HDP associated with high-grade patellofemoral chondromalacia in adults. HYPOTHESIS: A combination of proximal and distal realignment procedures of the patella will reduce pain and increase function in adult patients with HDP. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Twelve patients with 13 symptomatic cases of HDP of the knee underwent surgical treatment that included lateral release, medial retinaculum advancement, and the anteromedial tibial tubercle transfer procedure. The average period between dislocation and surgery was 10.8 years. One patient had an additional procedure, an open-wedge varus corrective osteotomy of the distal femur, because of a 20 degrees valgus deformity of the knee. The patellofemoral morphology study included routine and Merchant views of the knee and a computed tomography scan at full extension and at 30 degrees flexion of the knee, before the operation and at follow-up. Any associated intra-articular pathologic findings during the surgical procedure were addressed. Patellofemoral function was evaluated with the Kujala functional score before surgery and at the time of the final follow-up. RESULTS: Chondromalacia of the patella over the medial facet and central ridge was grade III in 8 knees and grade IV in 5 knees. Corresponding chondral erosion of the lateral femoral condyle was noted in every knee. All patients were followed for an average period of 67.3 months (range, 25-103 months). The average preoperative Kujala functional score was 43.9 and the average postoperative score was 88.9 (P< .05). Radiographically, there was a statistically significant improvement in the congruence angle from 62.1 degrees +/- 15.0 degrees preoperatively to -2.7 degrees +/- 9.8 degrees postoperatively (P< .01) and in the lateral patellofemoral angle from -40.2 degrees +/- 9.3 degrees preoperatively to 1.4 degrees +/- 7.0 degrees postoperatively (P< .01). No patient has reported an episode of patellar dislocation after the surgical procedures. CONCLUSION: Combined proximal and distal realignments of the patella effectively treat HDP in adults with associated high-grade patellofemoral chondromalacia. PMID- 17724091 TI - High-stiffness distal fixation restores anterior laxity and stiffness as well as joint line fixation with an interference screw. AB - BACKGROUND: Fixation of an anterior cruciate ligament graft at the joint line with an interference screw restores anterior laxity better than low-stiffness distal fixation with double staples and sutures tied to a post at implantation in porcine bone. HYPOTHESIS: Fixation of an anterior cruciate ligament graft with a high-stiffness distal fixation device restores anterior laxity and knee stiffness as well as joint line fixation with an interference screw in human bone. STUDY DESIGN: Controlled laboratory study. METHODS: Eleven cadaveric knees with foam reinforcement of the bone were reconstructed with a double-looped tendon graft and fixed with an interference screw and 3 high-stiffness methods of fixation (tandem washer, WasherLoc, and WasherLoc with bone dowel). Anterior laxity at 225 and 110 N of anterior load and knee stiffness were measured at 0 degrees , 30 degrees , 60 degrees , 90 degrees , and 120 degrees of flexion with a 6 degrees of freedom load application system. RESULTS: The increase in anterior laxity and knee stiffness with the interference screw was not significantly different from that with the high-stiffness distal methods. CONCLUSION: In the human knee, the use of high-stiffness fixation devices placed distal to the joint line restored anterior laxity and knee stiffness as well as joint line fixation with an interference screw at implantation. CLINICAL RELEVANCE: The stiffness provided by each method of fixation should be considered along with the length of the graft when determining anterior laxity and knee stiffness. PMID- 17724092 TI - Long-term follow-up and knee osteoarthritis change after medial patellofemoral ligament reconstruction for recurrent patellar dislocation. AB - BACKGROUND: Proximal or distal realignment procedures have long been selected as treatment for recurrent patellar dislocation, but associated knee osteoarthritis has been a substantial problem that leads to poor results. A new approach, medial patellofemoral ligament reconstruction, has recently started, but there have been no reports on the long-term follow-up. HYPOTHESIS: Anatomical medial patellofemoral ligament reconstruction can lead to satisfactory long-term outcome and a low association rate of knee osteoarthritis. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Twenty-four knees from 22 patients who underwent medial patellofemoral ligament reconstruction for recurrent patellar dislocation were reviewed at a mean follow-up of 11.9 years (range, 8.5-17.2 years). A lateral release was done on 14 of 24 knees. The clinical/physical outcome and the association of knee osteoarthritis were investigated. Patellofemoral and femorotibial osteoarthritis on the radiographs was evaluated using the Crosby/Insall and the Kellgren/Lawrence grading systems. RESULTS: According to the Crosby/Insall criteria, 11 knees (46%) were classified as excellent, 10 (42%) as good, 3 (12%) as fair/poor, and none as worse at follow-up. Further lateral subluxation or dislocation occurred in only 2 knees. The mean Kujala score improved significantly from 63.2 points preoperatively to 94.2 points at follow up (P < .0001). According to the Crosby/Insall grading system, patellofemoral osteoarthritis was none to mild in 23 of the 24 knees and moderate in 1 knee, pre operatively. At the final follow-up, 21 knees were none to mild, and 3 knees were moderate. There were only 2 knees that had definite progression from none to mild to a moderate grade. CONCLUSION: The association of definite knee osteoarthritis in medial patellofemoral ligament reconstruction with or without lateral release was small in the long-term follow-up. The conclusion is that medial patellofemoral ligament reconstruction not only prevents further patellar dislocation but also shows no or only slight progression of knee osteoarthritis. PMID- 17724093 TI - Donor site evaluation after autologous osteochondral mosaicplasty for cartilaginous lesions of the elbow joint. AB - BACKGROUND: One significant disadvantage of autologous osteochondral mosaicplasty (mosaicplasty) is the harvesting of osteochondral grafts from the normal articular area of the knee joint. However, the effect of harvesting grafts on knee function remains unclear. PURPOSE: To clarify the functional effects on the donor knee of harvesting osteochondral grafts and to perform magnetic resonance imaging evaluation of donor site repair after mosaicplasty for capitellar osteochondritis dissecans in young athletes. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Eleven male competitive athletes with advanced lesions of capitellar osteochondritis dissecans underwent mosaicplasties. The surgical technique involves obtaining small-sized cylindrical osteochondral grafts from the lateral periphery of the femoral condyle at the level of the patellofemoral joint and transplanting them to osteochondral defects in the capitellum. Assessment at a mean follow-up of 26 months included local findings of the donor knees, a Lysholm knee scoring scale, International Knee Documentation Committee standard evaluation form, and magnetic resonance imaging evaluation. RESULTS: All patients returned to a competitive level of their previous sports without any donor site disturbances. Based on the Lysholm knee score and International Knee Documentation Committee evaluation form, all knees were graded as excellent and normal, respectively. The magnetic resonance imaging showed 50% to 100% defect fill in 6 of 9 patients and normal or nearly normal signals in 4 patients at the donor sites. CONCLUSION: No adverse effects of osteochondral graft harvest on donor knee function were found after mosaicplasty for capitellar osteochondritis dissecans in young athletes. However, magnetic resonance imaging indicates that the donor site is resurfaced with fibrous tissue. PMID- 17724094 TI - Arthroscopic autologous osteochondral grafting for cartilage defects of the knee: prospective study results at a minimum 7-year follow-up. AB - BACKGROUND: Articular cartilage lesions, with their inherent limited healing potential, remain a challenging problem for orthopaedic surgeons. Various approaches have been proposed to treat these lesions; nevertheless, opinions on indications and clinical efficacy of these techniques are still controversial. PURPOSE: To evaluate the outcome of osteochondral autografts for treatment of femoral condyle cartilage lesions at a medium-to long-term follow-up. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: We prospectively evaluated 30 patients (mean age, 29.3 years) with full-thickness knee chondral lesions (<2.5 cm(2)) treated with arthroscopic autologous osteochondral transplantation. Thirteen patients underwent previous surgery, while 17 patients were operated on for the first time. In 19 patients, associated procedures were performed. All patients were evaluated at 2- and 7-year follow-up. The International Cartilage Repair Society form, Tegner score, and magnetic resonance imaging were used for clinical evaluation. RESULTS: The International Cartilage Repair Society objective evaluation showed 76.7% of patients had good or excellent results at 7 year follow-up, and International Knee Documentation Committee subjective score significantly improved from preoperative (34.8) to 7-year follow-up (71.8). The Tegner evaluation showed a significant improvement after the surgery at 2- and 7 year follow-up (from 2.9 to 6.2 and 5.6, respectively); however, we noticed reduced sports activity from 2- to 7-year follow-up. Magnetic resonance imaging evaluation showed good integration of the graft in the host bone and complete maintenance of the grafted cartilage in more than 60% of cases. CONCLUSION: The results of this technique at medium- to long-term follow-up are encouraging. This arthroscopic 1-step surgery appears to be a valid solution for treatment of small, grade III to IV cartilage defects. PMID- 17724095 TI - Analysis of cartilage tissue on a cellular level in fresh osteochondral allograft retrievals. AB - BACKGROUND: Fresh human osteochondral allografting is a biological cartilage replacement technique used to treat articular and osteoarticular defects in the knee. A small number of grafts fail, and we analyzed every retrieved graft during a 4-year period in order to learn more about the potential causes of failure. HYPOTHESIS: A large percentage of chondrocytes still remain viable many years after fresh osteochondral allografting. STUDY DESIGN: Descriptive laboratory study. METHODS: Retrieval specimens were obtained at the time of revision surgery and immediately analyzed. Chondrocyte viability and viable cell density were determined using a live/dead staining technique followed by confocal microscopy. Glycosaminoglycan content was a measure of the cartilage matrix. Radiolabeled sulfate uptake served as a biochemical marker of chondrocyte metabolic activity. Cartilage and subchondral bone were examined histologically. RESULTS: Fourteen patients yielded a total of 26 retrieval specimens that had been originally implanted as individual fresh osteochondral allografts. Average graft survival was 42 months. Chondrocyte viability was 82% +/- 17%, and chondrocyte viable cell density was 15 590 +/- 5900 viable cells/mm(3). Retrieved tissue demonstrated radiolabeled sulfate uptake of 437 +/- 270 counts per minute and 3.5% +/- 0.8% hexosamine per dry weight. Histologically, all specimens showed some degree of cartilage fibrillation. There was evidence of bone allograft incorporation in most specimens, as well as pannus formation in 4 specimens, but no evidence of immune rejection. CONCLUSION: A small percentage of fresh osteochondral allografts fail, but the precise cause is unknown. The main theories for failure investigated here include immunologic rejection, failure of bony incorporation, and chondrocyte death causing breakdown of the cartilage matrix. We show that chondrocytes remain viable many years after transplantation, allograft bone incorporates, and immune rejection does not seem to play a primary role in failure. CLINICAL RELEVANCE: Fresh osteochondral allografting is becoming more common in the treatment of articular cartilage defects in the knee. Our findings support the paradigm of fresh osteochondral allografting, the transplantation of hyaline cartilage with biological incorporation of the underlying bone scaffold. The reasons for failure of a small percentage of grafts remain unclear. PMID- 17724096 TI - Proximal tibial opening wedge osteotomy as the initial treatment for chronic posterolateral corner deficiency in the varus knee: a prospective clinical study. AB - BACKGROUND: Nonoperative treatment of posterolateral knee injuries tends to yield poor results. In patients with chronic posterolateral knee injuries, failure to correct genu varus alignment will often result in failure of the posterolateral knee repair or reconstruction. PURPOSE: To prospectively assess the functional outcomes of patients with combined grade 3 posterolateral instability and genu varus alignment initially treated with a proximal tibial opening wedge osteotomy. STUDY DESIGN: Cohort study (prognosis); Level of evidence, 2. METHODS: Twenty-one patients with combined chronic posterolateral corner deficiency and genu varus alignment were initially treated with a proximal tibial opening wedge osteotomy and observed prospectively. Second-stage ligamentous reconstruction was performed in patients with continued clinical and functional instability after the osteotomies had healed and they had undergone at least 3 months of rehabilitation. RESULTS: At a mean follow-up of 37 months, 8 of 21 patients (38%) had sufficient improvement in knee function that a subsequent posterolateral corner reconstruction was not necessary. There was a significant difference in coronal alignment between the preoperative and postoperative mechanical axis action point. There were no significant differences in the preoperative and postoperative posterior tibial slope. Thirteen patients underwent a second-stage ligament reconstruction at an average of 13.8 months after the initial osteotomy procedure. Final postoperative Cincinnati Knee Rating System scores were significantly lower for those patients who required a subsequent posterolateral corner reconstruction than for those patients who did not have a reconstruction. The P value for the preoperative differences between groups was not significant (P = .11). Seven of 9 patients with high-velocity knee injuries required a second stage reconstruction. Ten of 14 patients (71%) with multiligament knee injuries required a posterolateral corner reconstruction. In contrast, 4 of 6 patients (67%) with an isolated posterolateral corner injury did not require a second stage ligament reconstruction. CONCLUSION: Proximal tibial opening wedge osteotomy can be an effective first method of treatment for patients with chronic combined posterolateral knee injuries and genu varus alignment. Patients with low velocity knee injuries and isolated chronic posterolateral knee injuries may not require a second-stage soft tissue ligament reconstruction after healing the osteotomy and undergoing a program of rehabilitation. PMID- 17724097 TI - Does health research warrant the modification of qualitative methods? PMID- 17724098 TI - Hope is forked: hope, loss, treatments, and AIDS dementia. AB - In the HIV epidemic hope and loss are temporally structured according to pre, and post highly active antiretroviral therapies (HAART). AIDS dementia is a neurological condition on which HAART has had an important impact, yet this form of dementia has received little sociocultural attention. In this article, the author explores ethnographically personal hope from the perspective of "Matthew," a significant other to a person with AIDS dementia, and how treatments influence this. Hope is present in Matthew's narrative, but its nature is complex and fluctuates with the arrival and perceived failure of HAART. The author concludes by suggesting that hope in this context is forked, which is suggestive of the tenacious nature of hope in the context of AIDS dementia in the era of HAART. PMID- 17724099 TI - Lesbian body image perceptions: the context of body silence. AB - As are all women, lesbians are influenced by Western society's expectations of what a woman should look like. However, they are also influenced by the lesbian subculture. One of the author's aims was to explore how the sociocultural contexts in which lesbians belong influence their perceptions of body image. She purposively selected 20 lesbians and used constant comparative analysis to guide data collection and analyze the resulting transcribed interviews. The internalization of the dominant culture's beauty expectations coupled with the adoption of a lesbian identity caused the participants to contend with a multitude of oppressive mandates from both sociocultural contexts. The author interpreted the outcomes of these oppressions through the lens of stigma theory. The results of the stigma assisted in the development of the context of Body Silence. The study results might serve to provide a better understanding of lesbian body image as an important component of lesbians' mental health. PMID- 17724100 TI - Painful childhood: children living with juvenile arthritis. AB - In this article the author explores the everyday life and coping of children living with juvenile arthritis. The author considered the children as experts on their illness who can give valuable insights into illness management from a patient's perspective. This is in contrast to most research, which lets others, such as caregivers, speak in the place of children. She used an ethnographic approach with open-ended interviews and participant observation to capture the complexity of chronic illness's impact on everyday life. Results of the study indicate that living with juvenile arthritis entails a constant taking control over one's body and achieving normality in life. These children must negotiate between their protected status of being a sick child and their immense responsibility in illness management. The author suggests that existing research on adult chronic illness has only limited relevance to understanding children's illness experience and that further research with children is needed. PMID- 17724101 TI - Diaries written for ICU patients. AB - Diaries are written for critically ill patients, to help them understand their intensive care stay and come to terms with their illness. The aim of this content analysis of eight such diaries is to understand the potential benefits for patients and families of this care intervention. A main category emerged: Sharing throughout the ICU time. Four themes were identified: (a) Sharing the story, (b) Sharing the presence, (c) Sharing feelings, and (d) Sharing through support. The first theme reflects the narration of daily events. The second is the perceived presence of health professionals and family at the patient's bedside and the presence of the patient as a person through the diary entries. The third theme describes the expression of feelings as written throughout the text. The last theme refers to the support offered to the patient. The diaries reflect the commitment and care of contributors to the patients' welfare. PMID- 17724102 TI - Toward increased capacity for practice-based research among health professionals: implementing a multisite qualitative research project with dietitians. AB - Despite repeated efforts to encourage health professionals to conduct practice based research, including qualitative research, few practitioners have become active researchers. Mentoring, networking, and hands-on experience have been identified as potential approaches for changing this situation. In this article, the authors describe how they implemented a research mentoring/training component in a national study exploring Canadian dietitians' attitudes and practices with regard to obesity and weight management. They discuss the successes and challenges experienced by mentors and trainees, and provide recommendations for future initiatives to enhance capacity for qualitative, practice-based research among health care practitioners. PMID- 17724103 TI - Establishing terminal status in end-of-life discussions. AB - The communicative purpose of an end-of-life discussion is to change the goals of treatment for a terminal patient from therapeutic to comfort care. In this study, the authors present a comparative discourse analysis of end-of-life discussions that reached a consensus to change the goals of treatment and discussions that did not. They found that the presentation of medical information was subtly different across these discussions: Decision-making discussions were based on a consistent accumulation of negative evidence, whereas non-decision-making discussions were inconsistent in this respect, including mention of positive rather than negative outcomes of medical problems, discussion of possible treatment options, and mitigating summary statements. The authors note that end of-life discussions with these specific features do not progress to a decision to change the goals of treatment to comfort care. PMID- 17724104 TI - The incorporation of the HIV/AIDS identity into the self over time. AB - In the mid-1990s HIV/AIDS transitioned from a terminal illness to a chronic disease because of medical advances. In this qualitative study the author examines how people incorporate the HIV/AIDS identity into their selves at three points in time. Findings demonstrate a five-component process, including diagnosis, postdiagnosis turning point, immersion, post-immersion turning point, and integration. In addition, the disclosure process corresponds to a particular component of incorporation. The author makes comparisons with the incorporation process of other chronic illness. Findings augment the literature on HIV/AIDS, chronic illness, and identity and have practical implications for HIV/AIDS educators. PMID- 17724105 TI - Daughters caring for dying parents: a process of relinquishing. AB - Caring for elderly, dying parents is challenging for daughters as they try to balance other obligations and responsibilities. The purpose of this grounded theory study was to explain the domain of daughters' caregiving experiences in Newfoundland and Labrador, Canada. The primary author interviewed 12 women whose parents had died. Three types of turmoil (emotional, relational, and societal) emerged as the central issue for these women. The authors discovered a substantive theory of Relinquishing with interdependent processes of Keeping Vigil, Navigating Systems, Facing Loss, and an end process of Coming to Terms. In moving through the process of Relinquishing, social conditions of personal ideals, family expectations, and societal demands determine strategies employed by any one daughter to manage her turmoil. The findings fill a gap in knowledge related to daughters' caregiving for dying parents by contributing a theoretical framework that will inform women, health care providers, researchers, and health policy makers. PMID- 17724106 TI - "It's like . . . a confronting issue": life-changing narratives of young people. AB - In this article, the authors report on the narrative accounts given in interviews by 27 first-year university students in New South Wales, Australia, regarding their experiences of loss. The students were drawn from four campuses: a large city campus, a smaller urban campus, one outer metropolitan campus, and one rural campus. From participants' accounts, the researchers found that it was important for these students to organize their experience and make sense of it. In making sense, these students imposed meaning on their experiences and thereby constructed and reconstructed stories of loss to make better sense of their experience. The researchers recognized that within the interviews, they were positioned as an audience and that they were part of a reexperiencing of the narrative. In this sense, they were collaborators in the retelling of the narrative of a lived experience. PMID- 17724107 TI - Exploring the use of vignettes: from validity to trustworthiness. AB - In this article one of the authors presents her experience of using vignettes in an action research case study, with particular emphasis on their trustworthiness. The research was carried out with a group of health care professionals who were working together to improve preoperative education for patients awaiting a hip replacement in one National Health Service Trust in the United Kingdom. The authors describe the exploration of three types of vignette--napshots, portraits, and composites--as a means of collecting, analyzing, and representing data. They provide an example of each and briefly present their evaluative use by the health care professionals. The vignettes were constructed to provide one account of the truth that was representative of events. Within this representation was the writer, researcher, and reader feature. The vignettes stimulated reflection and analysis within the action research cycle and thus contributed to the improvement of practice. PMID- 17724108 TI - Everybody has a story: listening to imprisoned sexual offenders. AB - In this article the author addresses two basic questions found at the intersection of ethics and qualitative research methodology: Why are some people reluctant to share their stories? and Are there some people whose stories ought not to be heard? Focusing on imprisoned sexual offenders, the author argues that the establishment of trust in the research relationship is essential to creating safe places for people living with "problem experiences" to tell their stories. He also argues that however repugnant, the stories of society's worst offenders must be heard if we as a society are to better understand their actions and protect ourselves. PMID- 17724109 TI - Using focus groups to improve the validity of cross-national survey research: a study of physician decision making. AB - In this article, the authors demonstrate how qualitative methods can form a foundation for quantitative research by improving instrument validity, informing the data collection process, and improving cost-effectiveness in a study of physician decision making. To test terminology, applicability, and comprehension of a quantitative questionnaire for doctors in the United States and United Kingdom, each country's researchers conducted physician focus groups with questions organized around the experiment, including (a) validity of video vignettes of actor "patients," (b) population accessibility, (c) level of remuneration, (d) appropriate endorsement figure, and (e) question comprehension. Focus group data collected during instrument development and fieldwork planning streamlined processes and achieved cost efficiencies and effectiveness for the overall study. Beyond simply adding a post hoc qualitative component to an already free-standing quantitative methodology, focus groups were used in the study formulation, where the qualitative methodology was integrated into the process of developing a valid survey instrument. PMID- 17724110 TI - Walking the talk: how participatory interview methods can democratize research. AB - In this article, the author explores the importance of participatory, respectful, and community-specific approaches to research relationships across differences in social location and experience. Drawing on transcripts from group interviews with 6 young Aboriginal mothers from Vancouver's Downtown Eastside who had experienced substance use during pregnancy and fetal alcohol syndrome/fetal alcohol effects, she discusses three practical strategies used in her doctoral research to address the empirical and methodological implications of this work: the provision of honoraria, collaborating with community leaders in participant recruitment, and the use of shared analysis in group interviews. Shared analysis in the group interviews was integral to supporting policy analysis that challenges the privatization of mothering and substance use. Group interviews can benefit both the participants and the research, support womens' agency, and democratize the research process while mitigating the potential for the misrepresentation and appropriation of women's experiences. PMID- 17724111 TI - Carspecken's critical approach as a way to explore nursing leadership issues. AB - Nursing leaders are attempting to provide effective support for staff as well as optimal client care in the most challenging of times for the health care industry globally. Regardless of where leaders practice, their health care setting will have its own socially constructed way of getting the work done. In this article the authors suggest Carspecken's critical methodology, particularly his use of the pragmatic horizon, as a useful method to assist leaders in recognizing their own behaviors as a first step to providing leadership that is more emancipatory. The aim of this reflection and resulting action is increasing leadership effectiveness to improve health care outcomes. PMID- 17724114 TI - Endocrine-related resources from the National Institutes of Health. PMID- 17724113 TI - Carnitine-associated encephalopathy caused by long-term treatment with an antibiotic containing pivalic acid. AB - An 18-month-old boy was treated with an antibiotic containing pivalic acid for 6 months for intractable otitis media and then developed repeated convulsions and loss of consciousness. Laboratory data showed hypoglycemia and hypocarnitinemia. Intravenous administration of glucose was ineffective against the seizures and loss of consciousness. However, the patient regained consciousness and recovered soon after intravenous infusion of carnitine. To our knowledge, intravenous carnitine administration that contributed to marked improvements in neurologic deficit caused by administration of an antibiotic containing pivalic acid has not been reported previously. These findings indicate that long-term use of such antibiotics should be avoided. PMID- 17724112 TI - Management of hereditary angioedema in pediatric patients. AB - Hereditary angioneurotic edema is a rare disorder caused by the congenital deficiency of C1 inhibitor. Recurring angioedematous paroxysms that most commonly involve the subcutis (eg, extremities, face, trunk, and genitals) or the submucosa (eg, intestines and larynx) are the hallmarks of hereditary angioneurotic edema. Edema formation is related to reduction or dysfunction of C1 inhibitor, and conventional therapy with antihistamines and corticosteroids is ineffective. Manifestations occur during the initial 2 decades of life, but even today there is a long delay between the onset of initial symptoms and the diagnosis of hereditary angioneurotic edema. Although a variety of reviews have been published during the last 3 decades on the general management of hereditary angioneurotic edema, little has been published regarding management of pediatric hereditary angioneurotic edema. Thus, we review our experience and published data to provide an approach to hereditary angioneurotic edema in childhood. PMID- 17724115 TI - W. Zacheus Cande: Evolutionary biologist in cell biologist's clothing. Interview by Ruth Williams. AB - Zac Cande wants to get to the roots of cell division and cytoskeletal mechanics. PMID- 17724116 TI - Putting the glue in glia: Necls mediate Schwann cell axon adhesion. AB - Interactions between Schwann cells and axons are critical for the development and function of myelinated axons. Two recent studies (see Maurel et al. on p. 861 of this issue; Spiegel et al., 2007) report that the nectin-like (Necl) proteins Necl-1 and -4 are internodal adhesion molecules that are critical for myelination. These studies suggest that Necl proteins mediate a specific interaction between Schwann cells and axons that allows proper communication of the signals that trigger myelination. PMID- 17724117 TI - A Skp2 autoinduction loop and restriction point control. AB - We describe a self-amplifying feedback loop that autoinduces Skp2 during G1 phase progression. This loop, which contains Skp2 itself, p27(kip1) (p27), cyclin E cyclin dependent kinase 2, and the retinoblastoma protein, is closed through a newly identified, conserved E2F site in the Skp2 promoter. Interference with the loop, by knockin of a Skp2-resistant p27 mutant (p27(T187A)), delays passage through the restriction point but does not interfere with S phase entry under continuous serum stimulation. Skp2 knock down inhibits S phase entry in nontransformed mouse embryonic fibroblasts but not in human papilloma virus-E7 expressing fibroblasts. We propose that the essential role for Skp2-dependent degradation of p27 is in the formation of an autoinduction loop that selectively controls the transition to mitogen-independence, and that Skp2-dependent proteolysis may be dispensable when pocket proteins are constitutively inactivated. PMID- 17724118 TI - Three-dimensional arrangement of F-actin in the contractile ring of fission yeast. AB - The contractile ring, which is required for cytokinesis in animal and yeast cells, consists mainly of actin filaments. Here, we investigate the directionality of the filaments in fission yeast using myosin S1 decoration and electron microscopy. The contractile ring is composed of around 1,000 to 2,000 filaments each around 0.6 mum in length. During the early stages of cytokinesis, the ring consists of two semicircular populations of parallel filaments of opposite directionality. At later stages, before contraction, the ring filaments show mixed directionality. We consider that the ring is initially assembled from a single site in the division plane and that filaments subsequently rearrange before contraction initiates. PMID- 17724119 TI - Functional association of Sun1 with nuclear pore complexes. AB - Sun1 and 2 are A-type lamin-binding proteins that, in association with nesprins, form a link between the inner nuclear membranes (INMs) and outer nuclear membranes of mammalian nuclear envelopes. Both immunofluorescence and immunoelectron microscopy reveal that Sun1 but not Sun2 is intimately associated with nuclear pore complexes (NPCs). Topological analyses indicate that Sun1 is a type II integral protein of the INM. Localization of Sun1 to the INM is defined by at least two discrete regions within its nucleoplasmic domain. However, association with NPCs is dependent on the synergy of both nucleoplasmic and lumenal domains. Cells that are either depleted of Sun1 by RNA interference or that overexpress dominant-negative Sun1 fragments exhibit clustering of NPCs. The implication is that Sun1 represents an important determinant of NPC distribution across the nuclear surface. PMID- 17724120 TI - The yeast integral membrane protein Apq12 potentially links membrane dynamics to assembly of nuclear pore complexes. AB - Although the structure and function of components of the nuclear pore complex (NPC) have been the focus of many studies, relatively little is known about NPC biogenesis. In this study, we report that Apq12 is required for efficient NPC biogenesis in Saccharomyces cerevisiae. Apq12 is an integral membrane protein of the nuclear envelope (NE) and endoplasmic reticulum. Cells lacking Apq12 are cold sensitive for growth, and a subset of their nucleoporins (Nups), those that are primarily components of the cytoplasmic fibrils of the NPC, mislocalize to the cytoplasm. APQ12 deletion also causes defects in NE morphology. In the absence of Apq12, most NPCs appear to be associated with the inner but not the outer nuclear membrane. Low levels of benzyl alcohol, which increases membrane fluidity, prevented Nup mislocalization and restored the proper localization of Nups that had accumulated in cytoplasmic foci upon a shift to lower temperature. Thus, Apq12p connects nuclear pore biogenesis to the dynamics of the NE. PMID- 17724121 TI - A nuclear envelope protein linking nuclear pore basket assembly, SUMO protease regulation, and mRNA surveillance. AB - The nuclear pore complex (NPC) is both the major conduit for nucleocytoplasmic trafficking and a platform for organizing macromolecules at the nuclear envelope. We report that yeast Esc1, a non-NPC nuclear envelope protein, is required both for proper assembly of the nuclear basket, a structure extending into the nucleus from the NPC, and for normal NPC localization of the Ulp1 SUMO protease. In esc1Delta cells, Ulp1 and nuclear basket components Nup60 and Mlp1 no longer distribute broadly around the nuclear periphery, but co-localize in a small number of dense-staining perinuclear foci. Loss of Esc1 (or Nup60) alters SUMO conjugate accumulation and enhances ulp1 mutant defects. Similar to previous findings with Mlp1, both Esc1 and Ulp1 help retain unspliced pre-mRNAs in the nucleus. Therefore, these proteins are essential for proper nuclear basket function, which includes mRNA surveillance and regulation of SUMO protein dynamics. The results raise the possibility that NPC-localized protein desumoylation may be a key regulatory event preventing inappropriate pre-mRNA export. PMID- 17724122 TI - Deletion of tumor necrosis factor death receptor inhibits amyloid beta generation and prevents learning and memory deficits in Alzheimer's mice. AB - The tumor necrosis factor type 1 death receptor (TNFR1) contributes to apoptosis. TNFR1, a subgroup of the TNFR superfamily, contains a cytoplasmic death domain. We recently demonstrated that the TNFR1 cascade is required for amyloid beta protein (Abeta)-induced neuronal death. However, the function of TNFR1 in Abeta plaque pathology and amyloid precursor protein (APP) processing in Alzheimer's disease (AD) remains unclear. We report that the deletion of the TNFR1 gene in APP23 transgenic mice (APP23/TNFR1(-/-)) inhibits Abeta generation and diminishes Abeta plaque formation in the brain. Genetic deletion of TNFR1 leads to reduced beta-secretase 1 (BACE1) levels and activity. TNFR1 regulates BACE1 promoter activity via the nuclear factor-kappaB pathway, and the deletion of TNFR1 in APP23 transgenic mice prevents learning and memory deficits. These findings suggest that TNFR1 not only contributes to neurodegeneration but also that it is involved in APP processing and Abeta plaque formation. Thus, TNFR1 is a novel therapeutic target for AD. PMID- 17724123 TI - Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth. AB - Neurotrophins, such as NGF and BDNF, induce sustained activation of Rap1 small G protein and ERK, which are essential for neurite outgrowth. We show involvement of a GDP/GTP exchange factor (GEF) for Rap1, PDZ-GEF1, in these processes. PDZ GEF1 is activated by GTP-Rap1 via a positive feedback mechanism. Upon NGF binding, the TrkA neurotrophin receptor is internalized from the cell surface, passes through early endosomes, and arrives in late endosomes. A tetrameric complex forms between PDZ-GEF1, synaptic scaffolding molecule and ankyrin repeat rich membrane spanning protein which interacts directly with the TrkA receptor. At late endosomes, the complex induces sustained activation of Rap1 and ERK, resulting in neurite outgrowth. In cultured rat hippocampal neurons, PDZ-GEF1 is recruited to late endosomes in a BDNF-dependent manner involved in BDNF-induced neurite outgrowth. Thus, the interaction of PDZ-GEF1 with an internalized neurotrophin receptor transported to late endosomes induces sustained activation of both Rap1 and ERK and neurite outgrowth. PMID- 17724124 TI - Nectin-like proteins mediate axon Schwann cell interactions along the internode and are essential for myelination. AB - Axon-glial interactions are critical for the induction of myelination and the domain organization of myelinated fibers. Although molecular complexes that mediate these interactions in the nodal region are known, their counterparts along the internode are poorly defined. We report that neurons and Schwann cells express distinct sets of nectin-like (Necl) proteins: axons highly express Necl-1 and -2, whereas Schwann cells express Necl-4 and lower amounts of Necl-2. These proteins are strikingly localized to the internode, where Necl-1 and -2 on the axon are directly apposed by Necl-4 on the Schwann cell; all three proteins are also enriched at Schmidt-Lanterman incisures. Binding experiments demonstrate that the Necl proteins preferentially mediate heterophilic rather than homophilic interactions. In particular, Necl-1 on axons binds specifically to Necl-4 on Schwann cells. Knockdown of Necl-4 by short hairpin RNA inhibits Schwann cell differentiation and subsequent myelination in cocultures. These results demonstrate a key role for Necl-4 in initiating peripheral nervous system myelination and implicate the Necl proteins as mediators of axo-glial interactions along the internode. PMID- 17724125 TI - Unregulated actin polymerization by WASp causes defects of mitosis and cytokinesis in X-linked neutropenia. AB - Specific mutations in the human gene encoding the Wiskott-Aldrich syndrome protein (WASp) that compromise normal auto-inhibition of WASp result in unregulated activation of the actin-related protein 2/3 complex and increased actin polymerizing activity. These activating mutations are associated with an X linked form of neutropenia with an intrinsic failure of myelopoiesis and an increase in the incidence of cytogenetic abnormalities. To study the underlying mechanisms, active mutant WASp(I294T) was expressed by gene transfer. This caused enhanced and delocalized actin polymerization throughout the cell, decreased proliferation, and increased apoptosis. Cells became binucleated, suggesting a failure of cytokinesis, and micronuclei were formed, indicative of genomic instability. Live cell imaging demonstrated a delay in mitosis from prometaphase to anaphase and confirmed that multinucleation was a result of aborted cytokinesis. During mitosis, filamentous actin was abnormally localized around the spindle and chromosomes throughout their alignment and separation, and it accumulated within the cleavage furrow around the spindle midzone. These findings reveal a novel mechanism for inhibition of myelopoiesis through defective mitosis and cytokinesis due to hyperactivation and mislocalization of actin polymerization. PMID- 17724126 TI - Rapid default transition of CD4 T cell effectors to functional memory cells. AB - The majority of highly activated CD4 T cell effectors die after antigen clearance, but a small number revert to a resting state, becoming memory cells with unique functional attributes. It is currently unclear when after antigen clearance effectors return to rest and acquire important memory properties. We follow well-defined cohorts of CD4 T cells through the effector-to-memory transition by analyzing phenotype, important functional properties, and gene expression profiles. We find that the transition from effector to memory is rapid in that effectors rested for only 3 d closely resemble canonical memory cells rested for 60 d or longer in the absence of antigen. This is true for both Th1 and Th2 lineages, and occurs whether CD4 T cell effectors rest in vivo or in vitro, suggesting a default pathway. We find that the effector-memory transition at the level of gene expression occurs in two stages: a rapid loss of expression of a myriad of effector-associated genes, and a more gradual gain of expression of a cohort of genes uniquely associated with memory cells rested for extended periods. PMID- 17724127 TI - Blood leukocyte microarrays to diagnose systemic onset juvenile idiopathic arthritis and follow the response to IL-1 blockade. AB - Systemic onset juvenile idiopathic arthritis (SoJIA) represents up to 20% of juvenile idiopathic arthritis. We recently reported that interleukin (IL) 1 is an important mediator of this disease and that IL-1 blockade induces clinical remission. However, lack of specificity of the initial systemic manifestations leads to delays in diagnosis and initiation of therapy. To develop a specific diagnostic test, we analyzed leukocyte gene expression profiles of 44 pediatric SoJIA patients, 94 pediatric patients with acute viral and bacterial infections, 38 pediatric patients with systemic lupus erythematosus (SLE), 6 patients with PAPA syndrome, and 39 healthy children. Statistical group comparison and class prediction identified genes differentially expressed in SoJIA patients compared with healthy children. These genes, however, were also changed in patients with acute infections and SLE. An analysis of significance across all diagnostic groups identified 88 SoJIA-specific genes, 12 of which accurately classified an independent set of SoJIA patients with systemic disease. Transcripts that changed significantly in patients undergoing IL-1 blockade were also identified. Thus, leukocyte transcriptional signatures can be used to distinguish SoJIA from other febrile illnesses and to assess response to therapy. Availability of early diagnostic markers may allow prompt initiation of therapy and prevention of disabilities. PMID- 17724128 TI - Enhanced TLR-mediated NF-IL6 dependent gene expression by Trib1 deficiency. AB - Toll-like receptors (TLRs) recognize a variety of microbial components and mediate downstream signal transduction pathways that culminate in the activation of nuclear factor kappaB (NF-kappaB) and mitogen-activated protein (MAP) kinases. Trib1 is reportedly involved in the regulation of NF-kappaB and MAP kinases, as well as gene expression in vitro. To clarify the physiological function of Trib1 in TLR-mediated responses, we generated Trib1-deficient mice by gene targeting. Microarray analysis showed that Trib1-deficient macrophages exhibited a dysregulated expression pattern of lipopolysaccharide-inducible genes, whereas TLR-mediated activation of MAP kinases and NF-kappaB was normal. Trib1 was found to associate with NF-IL6 (also known as CCAAT/enhancer-binding protein beta). NF IL6-deficient cells showed opposite phenotypes to those in Trib1-deficient cells in terms of TLR-mediated responses. Moreover, overexpression of Trib1 inhibited NF-IL6-dependent gene expression by down-regulating NF-IL6 protein expression. In contrast, Trib1-deficient cells exhibited augmented NF-IL6 DNA-binding activities with increased amounts of NF-IL6 proteins. These results demonstrate that Trib1 is a negative regulator of NF-IL6 protein expression and modulates NF-IL6 dependent gene expression in TLR-mediated signaling. PMID- 17724131 TI - TCR-based lineage tracing: no evidence for conversion of conventional into regulatory T cells in response to a natural self-antigen in pancreatic islets. AB - Foxp3-expressing regulatory T (T reg) cells derive primarily from selection in the thymus. Yet conversion of mature conventional CD4(+) T (T conv) cell lymphocytes can be achieved in several conditions, such as transforming growth factor beta treatment, homeostatic expansion, or chronic exposure to low-dose antigen. Such conversion might provide a means to generate peripheral tolerance by "converting" potentially damaging T cells that react to self-antigens. We tested this hypothesis in mice transgenic for the BDC2.5 T cell receptor (TCR), which is representative of a diabetogenic specificity that is naturally present in NOD mice and reactive against a pancreatic self-antigen. In the thymus, before any exposure to antigen, clonotype-positive T reg and T conv cells express a second TCRalpha chain derived from endogenous loci. High-throughput single-cell sequencing of secondary TCRs of the Valpha2 family showed their joining CDR3alpha regions to be very different in T reg and T conv cell thymocytes. These specific CDR3alpha motifs, thus, provided a "tag" with which to test the actual impact of T conv to T reg cell conversion in response to peripheral self-antigen; should the autoreactive clonotypic TCR induce T conv to T reg cell conversion upon encounter of cognate antigen in the pancreas or draining lymph node, one would expect to detect tag CDR3alpha motifs from T conv cells in the T reg cell populations. Sequencing large numbers of peripheral BDC(+)Valpha2(+) cells showed that little to no conversion occurs in response to this pancreatic autoantigen. PMID- 17724130 TI - Progressive CD4+ central memory T cell decline results in CD4+ effector memory insufficiency and overt disease in chronic SIV infection. AB - Primary simian immunodeficiency virus (SIV) infections of rhesus macaques result in the dramatic depletion of CD4(+) CCR5(+) effector-memory T (T(EM)) cells from extra-lymphoid effector sites, but in most infections, an increased rate of CD4(+) memory T cell proliferation appears to prevent collapse of effector site CD4(+) T(EM) cell populations and acute-phase AIDS. Eventually, persistent SIV replication results in chronic-phase AIDS, but the responsible mechanisms remain controversial. Here, we demonstrate that in the chronic phase of progressive SIV infection, effector site CD4(+) T(EM) cell populations manifest a slow, continuous decline, and that the degree of this depletion remains a highly significant correlate of late-onset AIDS. We further show that due to persistent immune activation, effector site CD4(+) T(EM) cells are predominantly short lived, and that their homeostasis is strikingly dependent on the production of new CD4(+) T(EM) cells from central-memory T (T(CM)) cell precursors. The instability of effector site CD4(+) T(EM) cell populations over time was not explained by increasing destruction of these cells, but rather was attributable to progressive reduction in their production, secondary to decreasing numbers of CCR5(-) CD4(+) T(CM) cells. These data suggest that although CD4(+) T(EM) cell depletion is a proximate mechanism of immunodeficiency, the tempo of this depletion and the timing of disease onset are largely determined by destruction, failing production, and gradual decline of CD4(+) T(CM) cells. PMID- 17724129 TI - Thymic selection pathway regulates the effector function of CD4 T cells. AB - Recently, a new developmental pathway for CD4 T cells that is mediated by major histocompatibility complex class II-positive thymocytes was identified (Choi, E.Y., K.C. Jung, H.J. Park, D.H. Chung, J.S. Song, S.D. Yang, E. Simpson, and S.H. Park. 2005. Immunity. 23:387-396; Li, W., M.G. Kim, T.S. Gourley, B.P. McCarthy, D.B. Sant'angelo, and C.H. Chang. 2005. Immunity. 23:375-386). We demonstrate that thymocyte-selected CD4 (T-CD4) T cells can rapidly produce interferon gamma and interleukin (IL) 4 upon in vivo and in vitro T cell receptor stimulation. These T-CD4 T cells appear to be effector cells producing both T helper type 1 (Th1) and Th2 cytokines, and they maintain a potential to produce Th2 cytokines under Th1-skewing conditions in a signal transducer and activator of transcription 6-independent manner. The IL-4 mRNA level is high in CD4 single positive thymocytes if they are selected on thymocytes, which is at least partly caused by enhanced histone acetylation of the IL-4 locus. However, mice that can generate T-CD4 T cells showed attenuated immune responses in an allergen-induced airway inflammation model, suggesting a protective role for T-CD4 T cells during an airway challenge. Our results imply that this thymic selection pathway plays an important role in determining the effector function of the resulting CD4 cells and in regulating immune response. PMID- 17724132 TI - COX-2 suppresses tissue factor expression via endocannabinoid-directed PPARdelta activation. AB - Although cyclooxygenase (COX)-2 inhibitors (coxibs) are effective in controlling inflammation, pain, and tumorigenesis, their use is limited by the recent revelation of increased adverse cardiovascular events. The mechanistic basis of this side effect is not well understood. We show that the metabolism of endocannabinoids by the endothelial cell COX-2 coupled to the prostacyclin (PGI(2)) synthase (PGIS) activates the nuclear receptor peroxisomal proliferator activated receptor (PPAR) delta, which negatively regulates the expression of tissue factor (TF), the primary initiator of blood coagulation. Coxibs suppress PPARdelta activity and induce TF expression in vascular endothelium and elevate circulating TF activity in vivo. Importantly, PPARdelta agonists suppress coxib induced TF expression and decrease circulating TF activity. We provide evidence that COX-2-dependent attenuation of TF expression is abrogated by coxibs, which may explain the prothrombotic side-effects for this class of drugs. Furthermore, PPARdelta agonists may be used therapeutically to suppress coxib-induced cardiovascular side effects. PMID- 17724133 TI - MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival. AB - The innate immune system relies on evolutionally conserved Toll-like receptors (TLRs) to recognize diverse microbial molecular structures. Most TLRs depend on a family of adaptor proteins termed MyD88s to transduce their signals. Critical roles of MyD88-1-4 in host defense were demonstrated by defective immune responses in knockout mice. In contrast, the sites of expression and functions of vertebrate MyD88-5 have remained elusive. We show that MyD88-5 is distinct from other MyD88s in that MyD88-5 is preferentially expressed in neurons, colocalizes in part with mitochondria and JNK3, and regulates neuronal death. We prepared MyD88-5/GFP transgenic mice via a bacterial artificial chromosome to preserve its endogenous expression pattern. MyD88-5/GFP was detected chiefly in the brain, where it associated with punctate structures within neurons and copurified in part with mitochondria. In vitro, MyD88-5 co-immunoprecipitated with JNK3 and recruited JNK3 from cytosol to mitochondria. Hippocampal neurons from MyD88-5 deficient mice were protected from death after deprivation of oxygen and glucose. In contrast, MyD88-5-null macrophages behaved like wild-type cells in their response to microbial products. Thus, MyD88-5 appears unique among MyD88s in functioning to mediate stress-induced neuronal toxicity. PMID- 17724134 TI - A role for AID in chromosome translocations between c-myc and the IgH variable region. AB - Chromosome translocations between oncogenes and the region spanning the immunoglobulin (Ig) heavy chain (IgH) variable (V), diversity (D), and joining (J) gene segments (Ig V-J(H) region) are found in several mature B cell lymphomas in humans and mice. The breakpoints are frequently adjacent to the recombination signal sequences targeted by recombination activating genes 1 and 2 during antigen receptor assembly in pre-B cells, suggesting that these translocations might be the result of aberrant V(D)J recombination. However, in mature B cells undergoing activation-induced cytidine deaminase (AID)-dependent somatic hypermutation (SHM), duplications or deletions that would necessitate a double strand break make up 6% of all the Ig V-J(H) region-associated somatic mutations. Furthermore, DNA breaks can be detected at this locus in B cells undergoing SHM. To determine whether SHM might induce c-myc to Ig V-J(H) translocations, we searched for such events in both interleukin (IL) 6 transgenic (IL-6 tg) and AID( /-) IL-6 tg mice. Here, we report that AID is required for c-myc to Ig V-J(H) translocations induced by IL-6. PMID- 17724137 TI - MicroRNAs in tumorigenesis: a primer. AB - MicroRNAs (miRNAs) are a family of 21- to 25-nucleotide, noncoding small RNAs that primarily function as gene regulators. It is surprising that these tiny molecules, so diverse and consequential in their biological functions, have been hidden for so many years. Thanks to their discovery, cancer research has found a new arena. Aided by innovative molecular techniques, the research of miRNAs in oncology has progressed rapidly in recent years. miRNA abnormalities are becoming an emerging theme in cancer research. Specific functions of miRNAs, many of which are relevant to cancer development, are becoming apparent. The value of miRNAs in cancer classification and prognostication is being explored, and new therapeutic strategies targeting miRNAs are being developed. Because there is great promise that miRNA research will provide breakthroughs in the understanding of cancer pathogenesis and development of new valuable prognostic markers, pathologists should be adequately informed of this rapidly progressing field. Here, we offer a review on the basics of miRNA biology and the emerging role of miRNA in cancer pathogenesis, classification, and prognostication, including highlights of the involvement of specific miRNAs in different tumor types. PMID- 17724138 TI - Aldosterone induces elastin production in cardiac fibroblasts through activation of insulin-like growth factor-I receptors in a mineralocorticoid receptor independent manner. AB - Aldosterone is known to regulate electrolyte homeostasis, but it may also contribute to other processes, including the maladaptive remodeling of postinfarct hearts. Because aldosterone has been implicated in the stimulation of collagen production in the heart, we investigated whether it would also affect elastin deposition in cultures of human cardiac fibroblasts. We first demonstrated that treatment with 1 to 50 nmol/L aldosterone leads to a significant increase in collagen type I mRNA levels and in subsequent collagen fiber deposition. Pretreatment of cells with the mineralocorticoid receptor antagonist spironolactone, but not with the glucocorticoid receptor antagonist RU 486, inhibited collagen synthesis in aldosterone-treated cultures. Most importantly, we demonstrated that aldosterone also increases elastin mRNA levels, tropoelastin synthesis, and elastic fiber deposition in a dose-dependent manner. Strikingly, neither spironolactone nor RU 486 eliminated aldosterone-induced increases in elastin production. We further discovered that the proelastogenic effect of aldosterone involves a rapid increase in tyrosine phosphorylation of the insulin-like growth factor-I receptor and that the insulin-like growth factor I receptor kinase inhibitor AG1024 or an anti-insulin-like growth factor-I receptor-neutralizing antibody inhibits both insulin-like growth factor-I and aldosterone-induced elastogenesis. Thus, we have demonstrated for the first time that aldosterone, which stimulates collagen production through the mineralocorticoid receptor-dependent pathway, also increases elastogenesis via a parallel mineralocorticoid receptor-independent pathway involving I insulin-like growth factor-I receptor signaling. PMID- 17724139 TI - Snail family transcription factors are implicated in thyroid carcinogenesis. AB - E-Cadherin (CDH1) expression is reduced in thyroid carcinomas by primarily unknown mechanisms. In several tissues, SNAIL (SNAI1) and SLUG (SNAI2) induce epithelial-mesenchymal transition by altering target gene transcription, including CDH1 repression, but these transcription factors have not been studied in thyroid carcinoma. Recently, our group has provided direct evidence that ectopic SNAI1 expression induces epithelial and mesenchymal mouse tumors. SNAI1, SNAI2, and CDH1 expression were analyzed in thyroid-derived cell lines and samples of human follicular and papillary thyroid carcinoma by reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry. The effect of SNAI1 expression on CDH1 transcription was analyzed by reverse transcriptase-polymerase chain reaction and Western blotting in ori-3 cells. Thyroid carcinoma development was analyzed in CombitTA-Snail mice, in which SNAI1 levels are up-regulated. SNAI1 and SNAI2 were not expressed in cells derived from normal thyroid tissue, or in normal human thyroid samples, but were highly expressed in cell lines derived from thyroid carcinomas, in human thyroid carcinoma samples, and their metastases. SNAI1 expression in ori-3 cells repressed CDH1 transcription. Combi-TA mice developed papillary thyroid carcinomas, the incidence of which was increased by concomitant radiotherapy. In conclusion, SNAI1 and SNAI2 are ectopically expressed in thyroid carcinomas, and aberrant expression in mice is associated with papillary carcinoma development. PMID- 17724140 TI - BMP7, a putative regulator of epithelial homeostasis in the human prostate, is a potent inhibitor of prostate cancer bone metastasis in vivo. AB - Bone morphogenic protein 7 (BMP7) counteracts physiological epithelial-to mesenchymal transition, a process that is indicative of epithelial plasticity. Because epithelial-to-mesenchymal transition is involved in cancer, we investigated whether BMP7 plays a role in prostate cancer growth and metastasis. BMP7 expression in laser-microdissected primary human prostate cancer tissue was strongly down-regulated compared with normal prostate luminal epithelium. Furthermore, BMP7 expression in prostate cancer cell lines was inversely related to tumorigenic and metastatic potential in vivo and significantly correlated to E cadherin/vimentin ratios. Exogenous addition of BMP7 to human prostate cancer cells dose-dependently inhibited transforming growth factor beta-induced activation of nuclear Smad3/4 complexes via ALK5 and induced E-cadherin expression. Moreover, BMP7-induced activation of nuclear Smad1/4/5 signaling transduced via BMP type I receptors was synergistically stimulated in the presence of transforming growth factor beta, a growth factor that is enriched in the bone microenvironment. Daily BMP7 administration to nude mice inhibited the growth of cancer cells in bone. In contrast, no significant growth inhibitory effect of BMP7 was observed in intraprostatic xenografts. Collectively, our observations suggest that BMP7 controls and preserves the epithelial phenotype in the human prostate and underscore a decisive role of the tumor microenvironment in mediating the therapeutic response of BMP7. Thus, BMP7 can still counteract the epithelial-to-mesenchymal transition process in the metastatic tumor, positioning BMP7 as a novel therapeutic molecule for treatment of metastatic bone disease. PMID- 17724141 TI - Cooperation of the proapoptotic receptor agonist rhApo2L/TRAIL with the CD20 antibody rituximab against non-Hodgkin lymphoma xenografts. AB - Recombinant human rhApo2L/TRAIL selectively stimulates apoptosis in various cancer cells through its receptors DR4 and DR5, and is currently in clinical trials. Preclinical studies have established antitumor activity of rhApo2L/TRAIL in models of epithelial cancers; however, efficacy in non-Hodgkin lymphoma (NHL) models is not well studied. Of 7 NHL cell lines tested in vitro, rhApo2L/TRAIL stimulated apoptosis in BJAB, Ramos RA1, and DoHH-2 cells. Rituximab, a CD20 antibody used to treat certain types of NHL, augmented rhApo2L/TRAIL-induced caspase activation in Ramos RA1 and DoHH2 but not BJAB or SC-1 cells, through modulation of intrinsic rather than extrinsic apoptosis signaling. In vivo, rhApo2L/TRAIL and rituximab cooperated to attenuate or reverse growth of tumor xenografts of all 4 of these cell lines. Depletion of natural killer (NK) cells or serum complement substantially reduced combined efficacy against Ramos RA1 tumors, suggesting involvement of antibody-dependent cell- and complement mediated cytotoxicity. Both agents exhibited greater activity against disseminated than subcutaneous BJAB xenografts, and worked together to inhibit or abolish disseminated tumors and increase survival. Moreover, rhApo2L/TRAIL helped circumvent acquired rituximab resistance of a Ramos variant. These findings provide a strong rationale for clinical investigation of rhApo2L/TRAIL in combination with rituximab as a novel strategy for NHL therapy. PMID- 17724142 TI - Extracellular calcium sensing promotes human B-cell activation and function. AB - Calcium is a second messenger for many signaling pathways in B cells, but its role as a receptor ligand has not been well characterized. However, pulses of free calcium were found to cause the rapid release of internal calcium stores in normal human B cells. This response appeared to be mediated by a cell surface protein with receptor properties as it could be blocked by pretreatment with trypsin and with kinase and phospholipase Cgamma inhibitors. The calcium receptor on B cells was not the conventional calcium-sensing receptor (CaSR) since B cells did not express CaSR and calcium-induced responses could not be blocked by specific CaSR inhibitors. B-cell responses to extracellular calcium activated phosphoinositide-3 kinase/AKT, calcineurin, extracellular signal regulated kinase, p38 mitogen-activated protein kinase, protein kinase C, Ca(2+)/calmodulin kinase II, and nuclear factor-kappaB signaling pathways, and resulted in transcription of the early response gene, CD83. This extracellular calcium sensor enhanced B-cell responses to Toll-like receptor, B-cell receptor, and cytokine receptor agonists. These findings suggest a means by which B cells prepare to engage in immune responses by responding to calcium fluctuations in their environment. PMID- 17724143 TI - Acquired hematopoietic stem-cell disorders and mammalian size. AB - Hematopoietic stem cells (HSCs) can both self renew and differentiate into precursors of all types of blood cells. HSCs are divided into an active pool and a quiescent reserve. Cells selected for the active pool contribute to hematopoiesis for many years. Mutations in HSCs can lead to neoplasms such as chronic myeloid leukemia, although the risk of neoplastic HSC disorders varies across mammals. We use allometric scaling relations combined with mutation selection evolutionary dynamics to determine which mammalian species is most resistant to HSC disorders. We find that the advantage of large mammals at escaping the selective pressure of cancer cells is insufficient to overcome the increased risk of acquiring mutations. Hence, mutation dominates, which favors smaller stem-cell pools and, consequently, smaller mammals, since these minimize the development of mutations in the active stem-cell pool. Consequently, the smaller the active stem-cell pools, the better. PMID- 17724144 TI - Blunted hepcidin response to oral iron challenge in HFE-related hemochromatosis. AB - Inadequate hepcidin synthesis leads to iron overload in HFE-related hemochromatosis. We explored the regulation of hepcidin by iron in 88 hemochromatosis patients (61 C282Y/C282Y, 27 C282Y/H63D) and 23 healthy controls by analyzing urinary hepcidin before and 24 hours after a 65-mg oral iron dose. Thirty-four patients were studied at diagnosis and had iron overload, and 54 patients were iron depleted. At diagnosis, hepcidin values in C282Y homozygotes were similar to controls, whereas values in C282Y/H63D heterozygotes were higher (P = .02). However, the hepcidin/ferritin ratio was decreased in both homozygotes (P < .001) and heterozygotes (P = .017), confirming the inadequate hepcidin production for the iron load with both genotypes. In iron-depleted patients of both genotypes studied at a time remote from phlebotomy, basal hepcidin was still lower than in controls (P < .001 for C282Y/C282Y and P = .002 for heterozygotes). After an iron challenge, mean urinary hepcidin excretion increased in controls (P = .001) but not patients, irrespective of genotype and iron status. Significant hepcidin increase ( > or = 10 ng/mg creatinine) was observed in 74% of controls, 15% of homozygotes, and 32% of heterozygotes. The hepcidin response to oral iron is blunted in HFE-related hemochromatosis and not improved after iron depletion. The findings support the involvement of HFE in iron sensing and subsequent regulation of hepcidin. PMID- 17724145 TI - Perforin-dependent apoptosis functionally compensates Fas deficiency in activation-induced cell death of human T lymphocytes. AB - Activation-induced cell death (AICD) is involved in peripheral tolerance by controlling the expansion of repeatedly stimulated T cells via an apoptotic Fas (CD95; APO-1)-dependent pathway. The TNFRSF-6 gene encoding Fas is mutated in children suffering from autoimmune lymphoproliferative syndrome (ALPS), which is characterized by lymphoproliferation and autoimmunity. We examined AICD in Fas deficient T cells from ALPS patients. We showed that primary activated Fas deficient T cells die by apoptosis after repeated T cell antigen receptor (TCR) stimulation despite resistance to Fas-mediated cell death. This Fas-independent AICD was found to be mediated through a cytotoxic granules-dependent pathway. Cytotoxic granules-mediated AICD was also detected in normal T lymphocytes though to a lesser extent. As expected, the cytotoxic granules-dependent AICD was abolished in T cells from Rab27a- or perforin-deficient patients who exhibited defective granules-dependent cytotoxicity. Supporting an in vivo relevance of the cytotoxic granules-dependent AICD in ALPS patients, we detected an increased number of circulating T lymphocytes expressing granzymes A and B. Altogether, these data indicated that the cytotoxic granules-dependent cell death in ALPS may compensate for Fas deficiency in T lymphocytes. Furthermore, they identified a novel AICD pathway as a unique alternative to Fas apoptosis in human peripheral T lymphocytes. PMID- 17724146 TI - A Ser678Pro substitution in Fks1p confers resistance to echinocandin drugs in Aspergillus fumigatus. AB - An S678P substitution in Fks1p, the major subunit of glucan synthase, was sufficient to confer echinocandin resistance in Aspergillus fumigatus. The equivalent mutation in Candida spp. has been implicated in echinocandin resistance. This work demonstrates that modification of Fks1p is a conserved mechanism for echinocandin resistance in pathogenic fungi. PMID- 17724147 TI - Intracellular metabolism and persistence of the anti-human immunodeficiency virus activity of 2',3'-didehydro-3'-deoxy-4'-ethynylthymidine, a novel thymidine analog. AB - The therapeutic benefits of current antiretroviral therapy are limited by the evolution of drug-resistant virus and long-term toxicity. Novel antiretroviral compounds with activity against drug-resistant viruses are needed. 2',3' didehydro-3'-deoxy-4'-ethynylthymidine (4'-Ed4T), a novel thymidine analog, has potent anti-human immunodeficiency virus (HIV) activity, maintains considerable activity against multidrug-resistant HIV strains, and is less inhibitory to mitochondrial DNA synthesis in cell culture than its progenitor stavudine (D4T). We investigated the intracellular metabolism and anti-HIV activity of 4'-Ed4T. The profile of 4'-Ed4T metabolites was qualitatively similar to that for zidovudine (AZT), with the monophosphate metabolite as the major metabolite, in contrast to that for D4T, with relatively poor formation of total metabolites. The first phosphorylation step for 4'-Ed4T in cells was more efficient than that for D4T but less than that for AZT. The amount of 4'-Ed4T triphosphate (4' Ed4TTP) was higher than that of AZTTP at 24 h in culture. There was a dose dependent accumulation of 4'-Ed4T diphosphate and 4'-Ed4TTP on up-regulation of thymidylate kinase and 3-phosphoglycerate kinase expression in Tet-On RKO cells, respectively. The anti-HIV activity of 4'-Ed4T in cells persisted even after 48 h of drug removal from culture in comparison with AZT, D4T, and nevirapine (NVP). The order of increasing persistence of anti-HIV activity of these compounds after drug removal was 4'-Ed4T > D4T > AZT > NVP. In conclusion, with the persistence of 4'-Ed4TTP and persistent anti-HIV activity in cells, we anticipate less frequent dosing and fewer patient compliance issues than for D4T. 4'-Ed4T is a promising antiviral candidate for HIV type 1 chemotherapy. PMID- 17724148 TI - Dietary inclusion of colicin e1 is effective in preventing postweaning diarrhea caused by F18-positive Escherichia coli in pigs. AB - With worldwide concern over the use of antibiotics in animal agriculture and their contribution to the spread of antibiotic resistance, alternatives to conventional antibiotics are needed. Previous research in our laboratories has shown that colicin E1 is effective against some Escherichia coli strains responsible for postweaning diarrhea (PWD) in vitro. In this study we examined the efficacy of the dietary inclusion of colicin E1 in preventing experimentally induced PWD caused by F18-positive enterotoxigenic E. coli in young pigs. Twenty four weaned pigs (23 days of age), identified by genotyping to be susceptible to F18-positive E. coli infections, were individually housed and fed diets containing 0, 11, or 16.5 mg colicin E1/kg diet. Two days after the start of the trial, all animals were orally inoculated with 1 x 10(9) CFU of each of two F18 positive E. coli strains isolated from pigs with PWD. The dietary inclusion of colicin E1 decreased the incidence and severity of PWD caused by F18-positive enterotoxigenic E. coli and improved the growth performance of the piglets. Additionally, the reduced incidence of PWD due to dietary colicin E1, lowered the levels of expression of the genes for interleukin 1beta and tumor necrosis factor beta in ileal tissues from these animals. The dietary inclusion of colicin E1 may be an effective alternative to conventional antibiotics in the diets of weaning pigs for the prevention of PWD caused by F18-positive enterotoxigenic E. coli. PMID- 17724149 TI - Quinolone-mediated bacterial death. PMID- 17724150 TI - vanD and vanG-like gene clusters in a Ruminococcus species isolated from human bowel flora. AB - A vancomycin-resistant, anaerobic, gram-positive coccus containing the vanD and vanG-like genes (strain CCRI-16110) was isolated from a human fecal specimen during a hospital surveillance program to detect carriers of vancomycin-resistant enterococci. Comparison of the 16S rRNA gene sequence of strain CCRI-16110 with databases revealed a potentially novel Ruminococcus species that was most similar (<94% identity) to Clostridium and Ruminococcus species. Strain CCRI-16110 was highly resistant to vancomycin and teicoplanin (MICs of >256 microg/ml). The complete DNA sequence of the vanD cluster was most similar (98.2% identity) to that of Enterococcus faecium BM4339, containing the vanD1 allele. An intD gene with 99% identity with that of this E. faecium strain was found to be associated with the vanD gene cluster of this novel anaerobic bacterium. Strain CCRI-16110 also harbors genes encoding putative VanS(G), VanG, and VanT(G) proteins displaying 56, 73.6, and 55% amino acid sequence identity, respectively, compared to the corresponding proteins encoded by the vanG1 and vanG2 operons of Enterococcus faecalis BM4518 and N03-0233. This study reports for the first time an anaerobic bacterium containing the vanD gene cluster. This strain also harbors a partial vanG-like gene cluster. The presence of vanD- and vanG-containing anaerobic bacteria in the human bowel flora suggests that these bacteria may serve as a reservoir for the vanD and vanG vancomycin resistance genes. PMID- 17724151 TI - Comparative immunogenicities of frozen and refrigerated formulations of live attenuated influenza vaccine in healthy subjects. AB - The frozen version of live attenuated influenza vaccine (LAIV; FluMist) was compared with a newly licensed, refrigerated formulation, the cold-adapted influenza vaccine, trivalent (CAIV-T), for their immunogenicity, safety, and tolerability in healthy subjects 5 to 49 years of age. Eligible subjects were randomized 1:1 to receive CAIV-T or frozen LAIV. Subjects 5 to 8 years of age received two doses of vaccine 46 to 60 days apart; subjects 9 to 49 years of age received one dose of vaccine. Equivalent immunogenicities were defined as serum hemagglutination inhibition (HAI) geometric mean titer (GMT) ratios >0.5 and <2.0 for each of the three vaccine-specific strains. A total of 376 subjects 5 to 8 years of age and 566 subjects 9 to 49 years of age were evaluable. Postvaccination HAI GMT ratios were equivalent for CAIV-T and LAIV. The GMT ratios of CAIV-T/LAIV for the H1N1, H3N2, and B strains were 1.24, 1.02, and 1.00, respectively, for the 5- to 8-year-old age group and 1.14, 1.12, and 0.96, respectively, for the 9- to 49-year-old age group. Seroresponse/seroconversion rates (fourfold or greater rise) were similar in both age groups for each of the three vaccine strains. Within 28 days, the most frequent reactogenicity event in the CAIV-T and LAIV groups was runny nose/nasal congestion, which occurred at higher rates after dose 1 (44% and 42%, respectively) than after dose 2 (41% and 29%, respectively) in the 5- to 8-year-old group. Otherwise, the rates of adverse events (AEs) were similar between the treatment groups and the two age cohorts, with no serious AEs related to the study vaccines. The immunogenicities, reactogenicity events, and AEs were comparable for refrigerated CAIV-T and frozen LAIV. PMID- 17724152 TI - Variations in reverse transcriptase and RNase H domain mutations in human immunodeficiency virus type 1 clinical isolates are associated with divergent phenotypic resistance to zidovudine. AB - Mutations in the RNase H domain of human immunodeficiency virus type 1 RT have been reported to cause resistance to zidovudine (ZDV) in vitro. However, very limited data on the in vivo relevance of these mutations in patients exist to date. This study was designed to determine the relationship between mutations in the RNase H domain and viral susceptibility to nucleoside analogues. Viruses harboring complex thymidine analogue mutation (TAM) and nucleoside analogue mutation (NAM) profiles were evaluated for their phenotypic susceptibilities to ZDV, tenofovir (TNF), and the nonapproved nucleoside reverse transcriptase inhibitors (NRTIs) beta-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine (Reverset), beta-D-5-fluorodioxolane-cytosine, and apricitabine. As controls, viruses from NRTI-naive patients were also studied. The pol RT region (codons 21 to 250) of the viruses were sequenced and evaluated for mutations in the RNase H domain (codons 441 to 560) and the connection domain (codons 289 to 400). The results showed that viruses from patients failing multiple NRTI-containing regimens had distinct TAM and NAM profiles that conferred various degrees of resistance to ZDV (0.9- to >300-fold). Sequencing of the RNase H domain identified five positions (positions 460,468, 483, 512, and 519) at which extensive amino acid polymorphisms common in both wild-type viruses and viruses from treated patients were identified. No mutations were observed at positions 539 and 549, which have previously been associated with ZDV resistance. Mutations in the RNase H domain did not appear to correlate with the levels of phenotypic resistance to ZDV. Although some mutations were also observed in the connection domain, the simultaneous presence of the L74V and M184V mutations was the most significant determinant of phenotypic resistance to ZDV in patients infected with viruses with TAMs. PMID- 17724153 TI - Synergistic efficacy of the combination of ST-246 with CMX001 against orthopoxviruses. AB - The combination of ST-246 and hexadecyloxypropyl-cidofovir or CMX001 was evaluated for synergistic activity in vitro against vaccinia virus and cowpox virus (CV) and in vivo against CV. In cell culture the combination was highly synergistic against both viruses, and the results suggested that combined treatment with these agents might offer superior efficacy in vivo. For animal models, ST-246 was administered orally with or without CMX001 to mice lethally infected with CV. Treatments began 1, 3, or 6 days postinfection using lower dosages than previously used for single-drug treatment. ST-246 was given at 10, 3, or 1 mg/kg of body weight with or without CMX001 at 3, 1, or 0.3 mg/kg to evaluate potential synergistic interactions. Treatment beginning 6 days post viral inoculation with ST-246 alone only increased the mean day to death at 10 or 3 mg/kg but had no effect on survival. CMX001 alone also had no effect on survival. When the combination of the two drugs was begun 6 days after viral infection using various dosages of the two, a synergistic reduction in mortality was observed. No evidence of increased toxicity was noted with the combination either in vitro or in vivo. These results indicate that combinations of ST-246 and CMX001 are synergistic both in vitro and in vivo and suggest that combination therapy using ST-246 and CMX001 for treatment of orthopoxvirus disease in humans or animals may provide an additional benefit over the use of the two drugs by themselves. PMID- 17724154 TI - Mupirocin-resistant, methicillin-resistant Staphylococcus aureus strains in Canadian hospitals. AB - Mupirocin resistance in Staphylococcus aureus is increasingly being reported in many parts of the world. This study describes the epidemiology and laboratory characterization of mupirocin-resistant methicillin-resistant S. aureus (MRSA) strains in Canadian hospitals. Broth microdilution susceptibility testing of 4,980 MRSA isolates obtained between 1995 and 2004 from 32 Canadian hospitals was done in accordance with CLSI guidelines. The clinical and epidemiologic characteristics of strains with high-level mupirocin resistance (HLMup(r)) were compared with those of mupirocin-susceptible (Mup(s)) strains. MRSA strains were characterized by pulsed-field gel electrophoresis (PFGE) and typing of the staphylococcal chromosomal cassette mec. PCR was done to detect the presence of the mupA gene. For strains with mupA, plasmid DNA was extracted and subjected to Southern blot hybridization. A total of 198 (4.0%) HLMup(r) MRSA isolates were identified. The proportion of MRSA strains with HLMup(r) increased from 1.6% in the first 5 years of surveillance (1995 to 1999) to 7.0% from 2000 to 2004 (P < 0.001). Patients with HLMup(r) MRSA strains were more likely to have been aboriginal (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.5 to 9.4; P = 0.006), to have had community-associated MRSA (OR, 2.2; 95% CI, 1.0 to 5.0; P = 0.05), and to have been colonized with MRSA (OR, 1.7; 95% CI, 1.0 to 3.0; P = 0.04). HLMup(r) MRSA strains were also more likely to be resistant to fusidic acid (21% versus 4% for mupirocin-susceptible strains; P < 0.001). All HLMup(r) MRSA strains had a plasmid-associated mupA gene, most often associated with a 9 kb HindIII fragment. PFGE typing and analysis of the plasmid profiles indicate that both plasmid transmission and the clonal spread of HLMup(r) MRSA have occurred in Canadian hospitals. These results indicate that the incidence of HLMup(r) is increasing among Canadian strains of MRSA and that HLMup(r) MRSA is recovered from patients with distinct clinical and epidemiologic characteristics compared to the characteristics of patents with Mup(s) MRSA strains. PMID- 17724155 TI - In vitro activity of human beta-defensin 2 against Pseudomonas aeruginosa in the presence of tear fluid. AB - Pseudomonas aeruginosa causes vision-threatening keratitis and is difficult to treat due to emerging resistance. Human beta-defensin 2 (hBD-2) is an antimicrobial peptide expressed by ocular surface epithelia with broad-spectrum activity against various pathogens, including P. aeruginosa. The activity of hBD 2 against P. aeruginosa in the presence of human tears or NaCl was studied. In some experiments, tears were heat-inactivated, filtered, and separated into cationic/anionic fractions or mucin MUC5AC was removed by immunoprecipitation before use. Immunoprecipitation was performed to study the interaction between hBD-2 and MUC5AC. hBD-2 activity was reduced by 40 to 90% in the presence of 17.5 to 70% (vol/vol) tears. NaCl reduced hBD-2 activity, but at most it could account for only 36% of the inhibitory effect of tears. Heat inactivation and filtration attenuated the ability of tears to inhibit hBD-2 activity by 65 and 68%, respectively. Anionic tear fractions significantly reduced (86%) the activity of hBD-2, whereas only a 22% reduction was observed with the cationic fractions. In the absence of MUC5AC, the activity of hBD-2 was restored by 64%. Immunoprecipitation studies suggested that the loss of hBD-2 activity in tears is due to a direct binding interaction with MUC5AC. Our data showed that the antimicrobial activity of hBD-2 is sensitive to the presence of human tears and that this is partly due to the salt content and also the presence of MUC5AC. These data cast doubt on the effectiveness of hBD-2 as an antimicrobial peptide, and additional studies are required to conclusively elucidate its role in innate immunity at the ocular surface in vivo. PMID- 17724156 TI - An OXA-66/OXA-51-like carbapenemase and possibly an efflux pump are associated with resistance to imipenem in Acinetobacter baumannii. AB - We investigated the mechanisms involved in imipenem resistance in 23 clinical strains of Acinetobacter baumannii. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed the presence of a 30-kDa protein in imipenem-intermediate A. baumannii (IIAB) and imipenem-resistant A. baumannii (IRAB) strains; this protein was almost undetectable in imipenem-susceptible A. baumannii (ISAB) strains. The 30-kDa protein was identified as an OXA-51-like carbapenemase using two-dimensional gel electrophoresis and mass spectrometry. Similar to other recent findings, bla(OXA-51-like) genes were found to exist in all 23 clinical strains; however, the transcript levels of bla(OXA-51-like) in the IIAB and IRAB were higher than in the ISAB strains using reverse transcriptase PCR (RT-PCR) and real-time RT-PCR assays. This change was due to the presence of an insertion sequence, ISAba1, upstream of bla(OXA-51-like) in the IIAB and IRAB strains that was not present in the ISAB strains. The introduction of bla(OXA-66) (a bla(OXA-51)(-like) gene), identified in ISAB ab1254 and IRAB ab1266, into Escherichia coli TOP10 cells resulted in 3.95-fold and 7.90-fold elevations in resistance to imipenem, respectively. Furthermore, when ISAB ab8 and ISAB ab1254 and their in vitro-selected imipenem-resistant mutants ISAB ab8(r) and ISAB ab1254(r) were compared, the results showed no change in the bla(OXA-66)/bla(OXA-51-like) gene sequences, in expression of the gene, and in the outer membrane protein profiles. However, there was a four- to eightfold reduction in imipenem resistance upon adding carbonyl cyanide m chlorophenylhydrazone. Taken together, these results suggest that the OXA-66/OXA 51-like carbapenemase contributes to intrinsic resistance to imipenem; however, drug export by an efflux pump may be more important and/or occur more frequently in imipenem-resistant A. baumannii. Furthermore, this is the first report of a Taiwanese strain of an OXA-66/OXA-51-like carbapenemase that confers imipenem resistance in A. baumannii. PMID- 17724157 TI - Concentration-dependent Mycobacterium tuberculosis killing and prevention of resistance by rifampin. AB - Rifampin is a cornerstone of modern antituberculosis therapy. However, rifampin's half-life of 3 h is believed to limit its utility for intermittent therapy, so new congeners with long half-lives are being developed. Using an in vitro pharmacokinetic-pharmacodynamic model of tuberculosis, we examined the relationships between rifampin exposure, microbial killing of log-phase-growth Mycobacterium tuberculosis, and suppression of resistance. Rifampin's microbial killing was linked to the area under the concentration-time curve-to-MIC ratio. The suppression of resistance was associated with the free peak concentration (C(max))-to-MIC ratio and not the duration that the rifampin concentration was above MIC. Rifampin prevented resistance to itself at a free C(max)/MIC ratio of > or =175. The postantibiotic effect duration was > or =5.2 days and was most closely related to the C(max)/MIC ratio (r(2) = 0.96). To explain rifampin's concentration-dependent effect, we examined the kinetics of rifampin entry into M. tuberculosis. Rifampin achieved concentration-dependent intracellular steady state concentrations within 15 min. Our results suggest that doses of rifampin higher than those currently employed would optimize the effect of rifampin, if patients could tolerate them. Another major implication is that in the design of new rifampin congeners for intermittent therapy, the important properties may include (i) the efficient entry of the rifamycin into M. tuberculosis, (ii) the achievement of a free C(max)/MIC of >175 that can be tolerated by patients, and (iii) a long postantibiotic effect duration. PMID- 17724158 TI - Crystal structure of cefditoren complexed with Streptococcus pneumoniae penicillin-binding protein 2X: structural basis for its high antimicrobial activity. AB - Cefditoren is the active form of cefditoren pivoxil, an oral cephalosporin antibiotic used for the treatment of respiratory tract infections and otitis media caused by bacteria such as Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Klebsiella pneumoniae, and methicillin susceptible strains of Staphylococcus aureus. Beta-lactam antibiotics, including cefditoren, target penicillin-binding proteins (PBPs), which are membrane associated enzymes that play essential roles in the peptidoglycan biosynthetic process. To envision the binding of cefditoren to PBPs, we determined the crystal structure of a trypsin-digested form of PBP 2X from S. pneumoniae strain R6 complexed with cefditoren. There are two PBP 2X molecules (designated molecules 1 and 2) per asymmetric unit. The structure reveals that the orientation of Trp374 in each molecule changes in a different way upon the formation of the complex, but each forms a hydrophobic pocket. The methylthiazole group of the C-3 side chain of cefditoren fits into this binding pocket, which consists of residues His394, Trp374, and Thr526 in molecule 1 and residues His394, Asp375, and Thr526 in molecule 2. The formation of the complex is also accompanied by an induced-fit conformational change of the enzyme in the pocket to which the C-7 side chain of cefditoren binds. These features likely play a role in the high level of activity of cefditoren against S. pneumoniae. PMID- 17724159 TI - Prevalence and expression of the plasmid-mediated quinolone resistance determinant qnrA1. AB - Since its discovery, qnrA has been found in most common Enterobacteriaceae. Ciprofloxacin MICs conferred by different qnrA-positive plasmids could range from 0.1 microg/ml to 2 microg/ml in Escherichia coli J53. The reasons for different ciprofloxacin MICs conferred by qnrA have not been fully clarified. Five hundred forty-one consecutive gram-negative clinical strains that were resistant or intermediate to ciprofloxacin and that were isolated in Shanghai in 2005 were screened for qnrA by PCR. For qnrA-positive isolates, the transferability of quinolone resistance was determined by conjugation and mutations within the quinolone resistance-determining region (QRDR) of gyrA and parC. aac(6')-Ib-cr was detected and qnrA RNA expression was determined using real-time reverse transcription-PCR for transconjugants with different ciprofloxacin MICs. The qnrA gene was detected in 7 of the 541 clinical isolates. Quinolone resistance was transferred in four strains by conjugation. Mutations in the QRDR of gyrA and parC were detected in five qnrA-positive clinical strains with higher ciprofloxacin MICs. Of four qnrA-bearing plasmids in E. coli J53, pHS4 and pHS5 conferred ciprofloxacin MICs of 0.094 to 0.125 microg/ml; pHS3, which harbored the aac(6')-Ib-cr gene as well, conferred a ciprofloxacin MIC of 0.25 microg/ml, and pHS6, which had both the aac(6')-Ib-cr gene and a high expression level of qnrA, had a ciprofloxacin MIC of 1.0 microg/ml. The prevalence of qnrA appeared to be higher in Enterobacter cloacae than in other Enterobacteriaceae. The coexistence of qnrA and aac(6')-Ib-cr in a single plasmid and increased qnrA expression can account for the different levels of ciprofloxacin resistance seen in transconjugants. PMID- 17724160 TI - First report of the emergence of CTX-M-type extended-spectrum beta-lactamases (ESBLs) as the predominant ESBL isolated in a U.S. health care system. AB - CTX-M-type extended-spectrum beta-lactamases (ESBLs) have become increasingly common worldwide, with the notable exception of the United States, where TEM- and SHV-type ESBLs have appeared to predominate. We have noted the emergence of ESBLs in our health care system (the University Health System in San Antonio, TX), especially in Escherichia coli isolates, that preferentially hydrolyze cefotaxime rather than ceftazidime, suggesting the possibility of CTX-M-type enzymes. Microbiology laboratory records were reviewed to identify ESBL-producing isolates and to compare the diameters of ceftazidime disk diffusion zones of inhibition to cefotaxime zone diameters. All isolates had been initially detected and confirmed using the procedures recommended by the Clinical and Laboratory Standards Institute. A total of 94 stored ESBL-producing isolates recovered between January 2000 and June 2006 (predominately from blood and normally sterile fluids) were retrieved for further study and screened using PCR primers specific for the presence of CTX-M, TEM, and SHV ESBLs. Only small numbers of retained ESBL producing isolates were available for study in 2000 and 2002. The percentages of available ESBL-producing organisms in the following years were found to produce CTX-M enzymes: 2000, 25%; 2001, 10%; 2002, 0%; 2003, 60%; 2004, 69%; 2005, 89%; and 2006, 70%. The most common CTX-M-type ESBL was CTX-M-15, followed by CTX-M 16, CTX-M-8, and CTX-M-14. Comparing the disk diffusion zone diameters of cefotaxime and ceftazidime was helpful with the initial recognition of CTX-M producing E. coli, which had an average cefotaxime zone diameter 7 mm smaller than the ceftazidime zone. However, comparing ceftazidime and cefotaxime zones for CTX-M-producing Klebsiella spp. was not helpful with initial recognition. CTX M enzymes were also identified in Proteus mirabilis, Enterobacter spp., and Morganella morganii. Based on pulsed-field gel electrophoresis typing of the E. coli isolates, the CTX-M-producing isolates did not represent the spread of a single clone in the institution or in the community. In conclusion, CTX-M-type ESBLs are now the most common ESBL type isolated from patients in our health care system and may also be present but unrecognized in other U.S. locales. PMID- 17724161 TI - Electrostatic interaction of internal Mg2+ with membrane PIP2 Seen with KCNQ K+ channels. AB - Activity of KCNQ (Kv7) channels requires binding of phosphatidylinositol 4,5 bisphosphate (PIP(2)) from the plasma membrane. We give evidence that Mg(2+) and polyamines weaken the KCNQ channel-phospholipid interaction. Lowering internal Mg(2+) augmented inward and outward KCNQ currents symmetrically, and raising Mg(2+) reduced currents symmetrically. Polyvalent organic cations added to the pipette solution had similar effects. Their potency sequence followed the number of positive charges: putrescine (+2) < spermidine (+3) < spermine (+4) < neomycin (+6) < polylysine (>>+6). The inhibitory effects of Mg(2+) were reversible with sequential whole-cell patching. Internal tetraethylammonium ion (TEA) gave classical voltage-dependent block of the pore with changes of the time course of K(+) currents. The effect of polyvalent cations was simpler, symmetric, and without changes of current time course. Overexpression of phosphatidylinositol 4 phosphate 5-kinase Igamma to accelerate synthesis of PIP(2) attenuated the sensitivity to polyvalent cations. We suggest that Mg(2+) and other polycations reduce the currents by electrostatic binding to the negative charges of PIP(2), competitively reducing the amount of free PIP(2) available for interaction with channels. The dose-response curves could be modeled by a competition model that reduces the pool of free PIP(2). This mechanism is likely to modulate many other PIP(2)-dependent ion channels and cellular processes. PMID- 17724162 TI - Simulation of Ca2+ movements within the sarcomere of fast-twitch mouse fibers stimulated by action potentials. AB - Ca(2+) release from the sarcoplasmic reticulum (SR) of skeletal muscle takes place at the triadic junctions; following release, Ca(2+) spreads within the sarcomere by diffusion. Here, we report multicompartment simulations of changes in sarcomeric Ca(2+) evoked by action potentials (APs) in fast-twitch fibers of adult mice. The simulations include Ca(2+) complexation reactions with ATP, troponin, parvalbumin, and the SR Ca(2+) pump, as well as Ca(2+) transport by the pump. Results are compared with spatially averaged Ca(2+) transients measured in mouse fibers with furaptra, a low-affinity, rapidly responding Ca(2+) indicator. The furaptra Deltaf(CaD) signal (change in the fraction of the indicator in the Ca(2+)-bound form) evoked by one AP is well simulated under the assumption that SR Ca(2+) release has a peak of 200-225 microM/ms and a FDHM of approximately 1.6 ms (16 degrees C). Deltaf(CaD) elicited by a five-shock, 67-Hz train of APs is well simulated under the assumption that in response to APs 2-5, Ca(2+) release decreases progressively from 0.25 to 0.15 times that elicited by the first AP, a reduction likely due to Ca(2+) inactivation of Ca(2+) release. Recovery from inactivation was studied with a two-AP protocol; the amplitude of the second release recovered to >0.9 times that of the first with a rate constant of 7 s( 1). An obvious feature of Deltaf(CaD) during a five-shock train is a progressive decline in the rate of decay from the individual peaks of Deltaf(CaD). According to the simulations, this decline is due to a reduction in available Ca(2+) binding sites on troponin and parvalbumin. The effects of sarcomere length, the location of the triadic junctions, resting [Ca(2+)], the parvalbumin concentration, and possible uptake of Ca(2+) by mitochondria were also investigated. Overall, the simulations indicate that this reaction-diffusion model, which was originally developed for Ca(2+) sparks in frog fibers, works well when adapted to mouse fast-twitch fibers stimulated by APs. PMID- 17724163 TI - Phosducin regulates the expression of transducin betagamma subunits in rod photoreceptors and does not contribute to phototransduction adaptation. AB - For over a decade, phosducin's interaction with the betagamma subunits of the G protein, transducin, has been thought to contribute to light adaptation by dynamically controlling the amount of transducin heterotrimer available for activation by photoexcited rhodopsin. In this study we directly tested this hypothesis by characterizing the dark- and light-adapted response properties of phosducin knockout (Pd- / -) rods. Pd- / - rods were notably less sensitive to light than wild-type (WT) rods. The gain of transduction, as measured by the amplification constant using the Lamb-Pugh model of activation, was 32% lower in Pd- / - rods than in WT rods. This reduced amplification correlated with a 36% reduction in the level of transducin betagamma-subunit expression, and thus available heterotrimer in Pd- / - rods. However, commonly studied forms of light adaptation were normal in the absence of phosducin. Thus, phosducin does not appear to contribute to adaptation mechanisms of the outer segment by dynamically controlling heterotrimer availability, but rather is necessary for maintaining normal transducin expression and therefore normal flash sensitivity in rods. PMID- 17724164 TI - Acute downregulation of ENaC by EGF involves the PY motif and putative ERK phosphorylation site. AB - The epithelial sodium channel (ENaC) is expressed in a variety of tissues, including the renal collecting duct, where it constitutes the rate-limiting step for sodium reabsorption. Liddle's syndrome is caused by gain-of-function mutations in the beta and gamma subunits of ENaC, resulting in enhanced Na reabsorption and hypertension. Epidermal growth factor (EGF) causes acute inhibition of Na absorption in collecting duct principal cells via an extracellular signal-regulated kinase (ERK)-dependent mechanism. In experiments with primary cultures of collecting duct cells derived from a mouse model of Liddle's disease (beta-ENaC truncation), it was found that EGF inhibited short circuit current (Isc) by 24 +/- 5% in wild-type cells but only by 6 +/- 3% in homozygous mutant cells. In order to elucidate the role of specific regions of the beta-ENaC C terminus, Madin-Darby canine kidney (MDCK) cell lines that express beta-ENaC with mutation of the PY motif (P616L), the ERK phosphorylation site (T613A), and C terminus truncation (R564stop) were created using the Phoenix retroviral system. All three mutants exhibited significant attenuation of the EGF induced inhibition of sodium current. In MDCK cells with wild-type beta-ENaC, EGF induced inhibition of Isc (<30 min) was fully reversed by exposure to an ERK kinase inhibitor and occurred with no change in ENaC surface expression, indicative of an effect on channel open probability (P(o)). At later times (>30 min), EGF-induced inhibition of Isc was not reversed by an ERK kinase inhibitor and was accompanied by a decrease in ENaC surface expression. Our results are consistent with an ERK-mediated decrease in ENaC open probability and enhanced retrieval of sodium channels from the apical membrane. PMID- 17724165 TI - Neutrophil transepithelial migration in response to the chemoattractant fMLP but not C5a is phospholipase D-dependent and related to the use of CD11b/CD18. AB - In Crohn's disease and ulcerative colitis patients, the numbers of neutrophils recovered from stool directly correlates with the severity of disease, implying that neutrophils in the lumen contribute to the tissue destruction; therefore, it is important to understand the mechanisms behind transintestinal epithelial migration. Neutrophil transintestinal epithelial migration to fMLP is appreciated to be CD11b/CD18 integrin (Mac-1)-dependent, while we recently reported that migration to C5a is Mac-1-independent. Here, we investigated whether phospholipase D (PLD), a signaling molecule linked to chemoattractant activation of neutrophils, is necessary for both Mac-1-dependent and Mac-1-independent migration. Both fMLP and C5a increased neutrophil expression of the Mac-1 activation epitope, indicating PLD was activated. This up-regulation was dose dependently prevented by incubation of neutrophils in 1-butanol, an inhibitor of PLD activity. Despite this effect on Mac-1, 1-butanol did not prevent neutrophil migration across acellular filters. Incubation in 1-butanol did inhibit fMLP but not C5a-mediated migration across intestinal epithelial cell monolayers, showing that transepithelial migration to fMLP but not C5a is dependent on PLD. The addition of phosphatidic acid, a reaction product of PLD, partially restored fMLP mediated transepithelial migration in the presence of 1-butanol but not the migration of Mac-1-deficient neutrophil-differentiated HL-60 cells. Thus PLD control over expression of the Mac-1 activation epitope is critical for neutrophil migration to fMLP but not C5a. Moreover, as PLD controls other neutrophil functions, such as the oxidative response, degranulation, and protease release, we could exclude these functions as being important in neutrophil transepithelial migration to C5a. PMID- 17724166 TI - Analysis of ocular hypopigmentation in Rab38cht/cht mice. AB - PURPOSE: To characterize the ocular phenotype resulting from mutation of Rab38, a candidate gene for Hermansky-Pudlak syndrome. METHODS: Chocolate mice (cht, Rab38(cht/cht)) and control heterozygous (Rab38(cht/)(+)) and wild-type mice were examined clinically, histologically, ultrastructurally, and electrophysiologically. Mice homozygous for both the Rab38(cht) and the Tyrp1(b) alleles were similarly examined. RESULTS: Rab38(cht/cht) mice showed variable peripheral iris transillumination defects at 2 months of age. Patches of RPE hypopigmentation were noted clinically in 57% of Rab38(cht/cht) eyes and 6% of Rab38(cht/)(+) eyes. Rab38(cht/cht) mice exhibited thinning of the iris and RPE and larger b-wave amplitudes in the scotopic range when compared with the control animals. Compared with wild-type mice, Rab38(cht/cht) melanosomes were smaller and there were fewer in neuroectodermally derived retinal pigment epithelium; in neural crest-derived choroid melanocytes, they were smaller in size only. Mutation of both Rab38 and Tyrp1 produced mice with ocular and coat color pigment dilution greater than that seen with either mutation alone. Comprehensive clinical and pathologic analyses showed no other organ system or blood defects in Rab38(cht/cht) mice. CONCLUSIONS: Rab38(cht/cht) mice show ocular characteristics reminiscent of human oculocutaneous albinism, as well as iris and RPE thinning. The synergistic effects of the Rab38(cht) and Tyrp1(b) alleles suggest that TYRP1 is not the only target of RAB38 trafficking. This mouse line provides a useful model for studying melanosome biology and its role in human ocular diseases. PMID- 17724168 TI - Localization of D-beta-aspartic acid-containing proteins in human eyes. AB - PURPOSE: Biologically uncommon D-beta-aspartic acid (D-beta-Asp) has been detected in proteins from various human tissues in elderly donors. Previous studies have identified D-beta-Asp residues at four different specific sites in alpha-crystallin from aged human lenses and an increased amount of D-beta-Asp residues with age. D-beta-Asp is formed as a result of racemization and accumulates with age; therefore, it is thought to be a potential marker of aging. To reveal the role of the D-beta-Asp formation in the aging process of eyes, immunohistochemical localization of D-beta-Asp was investigated in ocular samples of various ages. METHODS: Polyclonal antibody to the D-beta-Asp-containing peptide was prepared. To confirm the specificity of the antibody, SDS-PAGE and Western blotting analyses of lens were performed. To detect the locality of the D beta-Asp-containing protein, immunohistochemical staining using the antibody was carried out in ocular samples obtained from nine donors 18 to 88 years of age and two fetuses. RESULTS: The antibody to the D-beta-Asp-containing peptide reacted with the lens peptide of the aged donors around 20 kDa that was compatible with alpha-A crystallin. In addition, the binding of the antibody to the alpha-A crystallin was almost completely blocked with the addition of the excess D-beta Asp-containing peptide. The antibody showed a negative reaction with any of the tissues in the eye of human fetuses and in donors younger than 18 years. In contrast, relatively strong immunoreactivity to the D-beta-Asp-containing peptides was seen in the nuclei of the lens, in nonpigmented ciliary epithelial cells, in drusen, and in the sclera of elderly donors. In addition, moderate to weak immunoreactivity was seen in the cortex of the lens, in the blood vessels of the retina, in the optic nerve head, and in the lamina cribrosa of elderly donors. Furthermore, the immunoreactions were almost completely blocked with the addition of the excess D-beta-Asp-containing peptide in the reaction mixture. CONCLUSIONS: The D-beta-Asp-containing proteins appeared in various ocular tissues with age. This study clearly demonstrated that the D-beta-Asp-containing proteins are more widespread in aged tissues than previously thought. The formation of D-beta-Asp in protein can cause major changes in its structure because different side chain orientations can induce an abnormal peptide backbone, and the main chain of the peptide can then become elongated by the beta linkage. Therefore, this modification can be the result of the partial unfolding of protein, leading to various age-related ocular diseases. In particular, D-beta Asp would provide a new aspect of the molecular mechanisms of age-related macular degeneration because drusen is positive for D-beta-Asp. PMID- 17724167 TI - Effects of foveal ablation on emmetropization and form-deprivation myopia. AB - PURPOSE: Because of the prominence of central vision in primates, it has generally been assumed that signals from the fovea dominate refractive development. To test this assumption, the authors determined whether an intact fovea was essential for either normal emmetropization or the vision-induced myopic errors produced by form deprivation. METHODS: In 13 rhesus monkeys at 3 weeks of age, the fovea and most of the perifovea in one eye were ablated by laser photocoagulation. Five of these animals were subsequently allowed unrestricted vision. For the other eight monkeys with foveal ablations, a diffuser lens was secured in front of the treated eyes to produce form deprivation. Refractive development was assessed along the pupillary axis by retinoscopy, keratometry, and A-scan ultrasonography. Control data were obtained from 21 normal monkeys and three infants reared with plano lenses in front of both eyes. RESULTS: Foveal ablations had no apparent effect on emmetropization. Refractive errors for both eyes of the treated infants allowed unrestricted vision were within the control range throughout the observation period, and there were no systematic interocular differences in refractive error or axial length. In addition, foveal ablation did not prevent form deprivation myopia; six of the eight infants that experienced monocular form deprivation developed myopic axial anisometropias outside the control range. CONCLUSIONS: Visual signals from the fovea are not essential for normal refractive development or the vision-induced alterations in ocular growth produced by form deprivation. Conversely, the peripheral retina, in isolation, can regulate emmetropizing responses and produce anomalous refractive errors in response to abnormal visual experience. These results indicate that peripheral vision should be considered when assessing the effects of visual experience on refractive development. PMID- 17724169 TI - Expression of JAM-A in the human corneal endothelium and retinal pigment epithelium: localization and evidence for role in barrier function. AB - PURPOSE: Junctional adhesion molecules (JAMs) are a family of adhesion proteins found in intercellular junctions. Evidence suggests that JAM-A is important for the regulation of tight junction assembly and epithelial barrier function. The authors recently reported that JAM-A is expressed in rabbit corneal endothelium and that antibody to JAM-A produces corneal swelling. In the present study, they investigate JAM-A expression in the human corneal endothelium and retinal pigment epithelium (RPE) and examine the effect of a function-blocking antibody to JAM-A on the permeability of cultured RPE cell monolayers. METHODS: Expression of JAM-A in human corneal endothelium, human RPE tissue, and cultured ARPE-19 monolayers was assessed by immunofluorescence confocal microscopy. Localization of JAM-A was compared with the tight junction-associated protein zonula occludens-1 (ZO-1). To investigate JAM-A function in ARPE-19 cells, ARPE-19 monolayers were subjected to a calcium switch protocol to disrupt cell junctions and treated with a function blocking antibody to JAM-A or an isotype-matched control. Dextran flux assays were performed to assess the effect of JAM-A antibody on ARPE-19 monolayer permeability. RESULTS: Expression of JAM-A was observed in human corneal endothelium, and its distribution correlated with the tight junction-associated protein ZO-1. In addition, expression of JAM-A was observed in human RPE and in intercellular junctions of ARPE-19 monolayers. The localization pattern of JAM-A in the RPE and ARPE-19 monolayers was similar to that of ZO-1. ARPE-19 monolayers treated with antibody to JAM-A demonstrated a 33% increase in permeability to 10,000 MWt dextran compared with monolayers treated with control antibody. CONCLUSIONS: Results of this study provide new information about JAM-A expression in tight junctions of the human corneal endothelium and human RPE. The observation that antibodies to JAM-A increase ARPE-19 monolayer permeability is consistent with previous findings of JAM-A function in epithelial tight junctions and suggests JAM-A may have a role in the regulation of RPE barrier function. PMID- 17724170 TI - Genetic heterogeneity in microcornea-cataract: five novel mutations in CRYAA, CRYGD, and GJA8. AB - PURPOSE: To unravel the molecular genetic background in families with congenital cataract in association with microcornea (CCMC, OMIM 116150). METHODS: CCMC families were recruited from a national database on hereditary eye diseases; DNA was procured from a national gene bank on hereditary eye diseases and by blood sampling from one large family. Genomewide linkage analysis, fine mapping, and direct genomic DNA sequencing of nine cataract candidate genes were applied. Restriction enzyme digests confirmed identified mutations. RESULTS: Analyses of 10 Danish families with hereditary congenital cataract and microcornea revealed five novel mutations. Three of these affected the crystallin, alpha-A gene (CRYAA), including two mutations (R12C and R21W) in the crystallin domain and one mutation (R116H) in the small heat shock domain. One mutation (P189L) affected the gap junction protein alpha 8 (GJA8), and one mutation (Y134X) was detected in crystallin gamma-D (CRYGD). CONCLUSIONS: The identification of a CRYGD mutation adds another gene to those that may be mutated in CCMC and underscores the genetic heterogeneity of this condition. Three CRYAA mutations at the R116 position, in association with CCMC, suggest that R116 represents a CCMC mutational hotspot. The CCMC phenotype demonstrates variable expression with regard to cataract morphology and age of appearance. Clinical heterogeneity, including additional malformation of the anterior segment of the eye, confirm that dedicated cataract genes may be involved in the largely unknown developmental molecular mechanisms involved in lens-anterior segment interactions. PMID- 17724171 TI - Detection of surfactant proteins A and D in human tear fluid and the human lacrimal system. AB - PURPOSE: To evaluate the expression and presence of surfactant protein (SP) A and SP-D in the lacrimal apparatus, at the ocular surface, and in tears in healthy and pathologic states. METHODS: Expression of mRNA for SP-A and SP-D was analyzed by RT-PCR in healthy lacrimal gland, conjunctiva, cornea, and nasolacrimal ducts as well as in a spontaneously immortalized conjunctival epithelial cell line (HCjE; IOBA-NHC) and a SV40-transfected cornea epithelial cell line (HCE). Deposition of SP-A and SP-D was determined by Western blot, dot blot, and immunohistochemistry in healthy tissues, in tears, aqueous humor, and in sections of different corneal abnormalities (keratoconus, herpetic keratitis, and Staphylococcus aureus-based ulceration). Cell lines were stimulated with different cytokines and bacterial components and were analyzed for the production of SP-A and SP-D by immunohistochemistry. RESULTS: The presence of SP-A and SP-D on mRNA and protein levels was evidenced in healthy lacrimal gland, conjunctiva, cornea, and nasolacrimal duct samples. Moreover, both proteins were present in tears but were absent in aqueous humor. Immunohistochemistry revealed the production of both peptides by acinar epithelial cells of the lacrimal gland and epithelial cells of the conjunctiva and nasolacrimal ducts, whereas goblet cells revealed no reactivity. Healthy cornea revealed weak reactivity on epithelial surface cells only. In contrast, SP-A and SP-D revealed strong reactivity in patients with herpetic keratitis and corneal ulceration surrounding lesions and in several immigrated defense cells. Reactivity in corneal epithelium and endothelium was also seen in patients with keratoconus. Cell culture experiments revealed that SP-A and SP-D are produced by both epithelial cell lines without and after stimulation with cytokines and bacterial components. CONCLUSIONS: These results show that SP-A, in addition to SP-D, is a peptide of the tear film. Based on the known direct and indirect antimicrobial effects of collectins, the surfactant-associated proteins A and D seem to be involved in several ocular surface diseases. PMID- 17724172 TI - AAV-mediated expression targeting of rod and cone photoreceptors with a human rhodopsin kinase promoter. AB - PURPOSE: Gene therapy for retinal degeneration requires well-defined promoters that drive expression in rod and cone photoreceptors. This study was undertaken to develop short, active derivatives of the human rhodopsin kinase (RK) gene promoter for targeting transgene expression in rods and cones. RK, also known as G protein-coupled receptor kinase 1 (GRK1), is a component of the light adaptation pathway expressed in rods and cones. METHODS: Human RK (hRK) promoter and its concatemers or derivatives extending into the conserved 5' untranslated region (5'-UTR) were assayed for promoter activity in WERI retinoblastoma or Crx/Sp1-supplemented HEK-293 cells. The derivative displaying the highest activity was linked to a GFP reporter and packaged in a pseudotyped adenoassociated viral vector (AAV2/5). The AAV vector was tested in vivo by subretinal injections in wild-type mice, in the all-cone Nrl(-/-) mice, and in the cone-rich diurnal Nile grass rat (Arvicanthis niloticus). Control eyes received a similar AAV2/5 vector carrying a mouse rod opsin (mOps) promoter controlled GFP reporter. RESULTS: The hRK promoter with the full 5' untranslated sequence (-112 to +180) was the most active in cell culture. Delivered by the AAV2/5 vector, RK promoter drove GFP expression specifically in photoreceptors. In rods, hRK promoter-mediated expression was as efficient as, but appeared more uniform than, mOps promoter-mediated expression. In cones, the hRK promoter drove expression, whereas the mOps promoter did not. CONCLUSIONS: The hRK promoter is active and specific for rod and cone photoreceptors. Because of its small size and proven activity in cones, it is a promoter of choice for somatic gene transfer and gene therapy targeting rods and cones. PMID- 17724173 TI - Prediction and verification of miRNA expression in human and rat retinas. AB - PURPOSE: MicroRNAs (miRNAs) play a global role in regulating gene expression and have important tissue-specific functions. Little is known about their role in the retina. The purpose of this study was to establish the retinal expression of those miRNAs predicted to target genes involved in vision. METHODS: miRNAs potentially targeting important "retinal" genes, as defined by expression pattern and implication in disease, were predicted using a published algorithm (TargetScan; Envisioneering Medical Technologies, St. Louis, MO). The presence of candidate miRNAs in human and rat retinal RNA was assessed by RT-PCR. cDNA levels for each miRNA were determined by quantitative PCR. The ability to discriminate between miRNAs varying by a single nucleotide was assessed. The activity of miR 124 and miR-29 against predicted target sites in Rdh10 and Impdh1 was tested by cotransfection of miRNA mimics and luciferase reporter plasmids. RESULTS: Sixty seven miRNAs were predicted to target one or more of the 320 retinal genes listed herein. All 11 candidate miRNAs tested were expressed in the retina, including miR-7, miR-124, miR135a, and miR135b. Relative levels of individual miRNAs were similar between rats and humans. The Rdh10 3'UTR, which contains a predicted miR 124 target site, mediated the inhibition of luciferase activity by miR-124 mimics in cell culture. CONCLUSIONS: Many miRNAs likely to regulate genes important for retinal function are present in the retina. Conservation of miRNA retinal expression patterns from rats to humans supports evidence from other tissues that disruption of miRNAs is a likely cause of a range of visual abnormalities. PMID- 17724174 TI - Ferritin H- and L-chains in fiber cell canine and human lenses of different ages. AB - PURPOSE: This study was designed to elucidate potential age-related changes in the concentration, structure, and assembly pattern of ferritin chains in lens fiber cells. METHODS: Canine and human lens fiber cell homogenate proteins were separated by one-dimensional and two-dimensional SDS-PAGE. Ferritin chains were immunodetected and quantitated with ferritin chain-specific antibodies. Total ferritin concentration was measured by ELISA. Binding of iron was determined in vitro with (59)Fe. RESULTS: Ferritin H- and L-chains in canine and human fiber cells of healthy lenses were extensively modified. The H-chain in both species was truncated, and its concentration increased with age. Canine L-chain was approximately 11 kDa larger than standard canine L-chain, whereas human L-chain was of the proper size. Two-dimensional separation revealed age-related polymorphism of human and canine lens fiber cell L-chains and human H-chains. Normal size ferritin chains were not identified in canine fiber cells, but a small amount of fully assembled ferritin was detected, and its concentration decreased with age. CONCLUSIONS: Such significantly altered ferritin chains are not likely to form functional ferritin capable of storing iron. Therefore, lens fiber cells, particularly from older lenses, may have limited ability to protect themselves against iron-catalyzed oxidative damage. PMID- 17724175 TI - Modified saponification and HPLC methods for analyzing carotenoids from the retina of quail: implications for its use as a nonprimate model species. AB - PURPOSE: To investigate carotenoid content in the retina of Japanese quail (Coturnix japonica), for comparison with carotenoids in human retina, and to assess the effects of different saponification procedures on the recovery of quail retinal carotenoids. METHODS: Extracted retinal carotenoids were saponified with methods adapted from recent studies, then identified and quantified with reverse-phase high-performance liquid chromatography (HPLC). To assess the effects of saponification conditions on carotenoid recovery from quail retina, we varied base concentration and the total time of saponification across a wide range and again used HPLC to compare carotenoid concentrations among conditions. RESULTS: Astaxanthin and galloxanthin were the dominant carotenoids recovered in the quail retina, along with smaller amounts of five other carotenoids (lutein, zeaxanthin, 3'-epilutein, epsilon-carotene, and an unidentified carotenoid). Astaxanthin was sensitive to saponification conditions; recovery was poor with strong bases (0.2 and 0.5 M KOH) and best with weak bases (0.01 and 0.2 M KOH). In contrast, xanthophyll carotenoids (galloxanthin, zeaxanthin, lutein, 3' epilutein, and the unknown) were best recovered with strong base after 6 hours of saponification at room temperature. The recovery of epsilon-carotene was not affected by saponification conditions. CONCLUSIONS: Separate chemical hydrolysis procedures--using a strong base to recover xanthophylls and a weak base to recover astaxanthin--should be used for maximizing recovery of quail retinal carotenoids. Because the dominant carotenoids in quail retina are absent in human retina, and because of their different packaging (e.g., esterified in oil droplets) and light-absorbance properties compared with xanthophylls in the human eye, use of the quail as a model organism for studying human retinal carotenoids should be approached with caution. PMID- 17724176 TI - Progression of diabetic macular edema: correlation with blood retinal barrier permeability, retinal thickness, and retinal vessel diameter. AB - PURPOSE: To study the progression of diabetic macular edema (DME) in relation to baseline retinal thickness, retinal vascular leakage, and retinal trunk vessel diameters. METHODS: In this single-center study, 45 patients were enrolled with 62 eligible eyes defined as having DME of a grade less than clinically significant macular edema (CSME). From the start, the patients were included in a multicenter study exploring the effect of ruboxistaurin versus placebo for 3.4 years. Subsequently, the patients were followed up for a mean of 5.7 years by optical coherence tomography, fundus photography, and vitreous fluorometry. Baseline values in eyes that progressed to photocoagulation treatment were compared with values from eyes that did not reach this endpoint. RESULTS: In the 22 eyes of 18 patients in which CSME was diagnosed and treated, mean retinal vascular leakage at baseline was 5.6 (95% CI 4.2-7.6) nm/s, whereas eyes that did not progress to photocoagulation had a significantly lower mean leakage at baseline of 3.4 (95% CI 2.7-4.3) nm/s. No significant difference was found for measures of baseline retinal thickness or summarized retinal trunk vessel diameters. Eyes that progressed to photocoagulation treatment (mean delay to treatment, 3.6 years) had significantly higher foveal thicknesses than did nonprogressing eyes, from 18 months after study initiation. CONCLUSIONS: Progression to photocoagulation treatment for CSME was associated with higher retinal vascular leakage at baseline, whereas baseline retinal vessel diameters and retinal thickness were comparable in progressing and nonprogressing eyes. Baseline leakage was the strongest predictor of progression from non-CSME to photocoagulation for CSME. PMID- 17724177 TI - Estimating the amount of mental effort required for independent mobility: persons with glaucoma. AB - PURPOSE: To validate the use of the secondary-task method to estimate the amount of mental effort required for independent travel and to determine how the amount of mental effort varies with characteristics of the environment. METHODS: Reaction time (RT) to a secondary task (randomly presented vibrations) was obtained in 28 persons with glaucoma as they walked in four different environments: hallway, high-pedestrian area, approach-to-stairs area, and stairs. Cronbach's alpha was used to assess the reliability of the secondary-task RT measures from the split-half measures of the high-pedestrian area. The construct validity of the RT measures as an estimate of mental effort was assessed by (1) the association between the RT scores and the item measure scores for similar environments derived from a Rasch analysis of perceived difficulty ratings obtained in a separate group of 83 persons with glaucoma and (2) the association between the RT scores and the severity of visual field loss. RESULTS: Reliability was supported by a Cronbach's alpha coefficient of 0.89. Construct validity was also supported by the data: (1) Log RT scores were linearly related to the Rasch analysis item measures for comparable mobility situations (P = 0.008), and (2) the log RT, averaged across the four environments, was linearly related to the mean deviation score of the Humphrey Visual Field Analyzer (estimate of visual field loss; P = 0.003; Carl Zeiss Meditec, Inc., Dublin, CA). A comparison of the log RT scores obtained in the four environments showed significantly higher log RT scores in the stairs area than in the high-pedestrian and hallway environments, whereas the log RT scores in the high-pedestrian and hallway environments were not significantly different. CONCLUSIONS: The findings in this study demonstrate the reliability and construct validity of the secondary-task RT measure as an estimate of the amount of mental effort required to travel independently. It is sensitive to environmental characteristics and the loss in a walker's visual field. The method could be an objective way to document those who may benefit from professional intervention and to evaluate the effectiveness of an intervention. PMID- 17724178 TI - The impact of optical factors on resolution acuity in children with Down syndrome. AB - PURPOSE: Down syndrome (DS) is associated with reduced visual acuity that cannot be explained by motivational or attentional factors. To isolate the contribution of optical factors to visual performance in DS, two types of resolution acuity were measured: grating resolution acuity, which is limited by optical quality, and interferometric acuity, which effectively bypasses the optics of the eye. METHODS: Twenty-nine children with DS (age range, 9-16 years) were tested. Sixty eight age-matched, developmentally healthy children acted as controls. All wore best refractive correction, and none had clinically significant ocular disease. Grating resolution and interferometric acuity were measured according to a two alternative, forced-choice procedure. RESULTS: There was no change in grating resolution acuity or interferometric acuity with age in either group. Mean grating resolution acuities were -0.12 log of the minimum angle of resolution (logMAR; SD +/- 0.07) for the control group and +0.48 logMAR (SD +/- 0.09) for the DS group. Mean interferometric acuities were -0.11 logMAR (SD +/- 0.08) for the control group and +0.004 (SD +/- 0.06) for the DS group. In the DS group, the mean interferometric acuity was reduced by a factor of 1.3, whereas mean grating resolution acuity was substantially reduced, by a factor of 4.1, compared with controls. CONCLUSIONS: Grating resolution and interferometric thresholds are reduced in children with DS. However the discrepancy between developmentally healthy children and those with DS is greater for grating resolution acuity, suggesting that degradation in optical quality is a major contributor to poor visual performance in children with DS. PMID- 17724180 TI - Exposure to Chlamydia pneumoniae infection and age-related macular degeneration: the Blue Mountains Eye Study. AB - PURPOSE: To assess cross-sectional and longitudinal associations between exposure to Chlamydia pneumoniae infection and age-related macular degeneration (AMD) in the nested case-control sample drawn from the Blue Mountains Eye Study (BMES) cohort. METHODS: The BMES examined 3654 persons aged 49 to 97 years during 1992 through 1994 (BMES I survey). Survivors from this cohort (n = 2335; 75%) and 1174 persons who moved in this area or reached an eligible age were examined during 1997 through 2000 (BMES II survey, n = 3509). One hundred ninety-seven AMD cases and 433 control subjects matched for age, sex and smoking status, were drawn from the BMES II survey. Photographic macular grading followed the Wisconsin grading system. Plasma samples were analyzed with an enzyme-linked immunosorbent assay to determine antibody titers to the elementary bodies from C. pneumoniae AR39. Associations between seroreactivity to C. pneumoniae and prevalent and incident AMD were assessed by using logistic regression models. RESULTS: There were 159 early and 38 late AMD cases. Of them, 87 cases of early and 22 of late AMD developed between the baseline and follow-up examinations. After adjustment for age, gender, and smoking, no significant association was evident between C. pneumoniae antibody titer and any prevalent early or late AMD (OR 1.02, 95% CI 0.66-1.56 comparing upper with lower tertile of antibody titer). Findings were similar when early or late AMD was analyzed separately. Analysis confined to incident AMD also showed no significant association with the incidence of either early (OR 0.92, 95% CI 0.52-1.64) or late (OR 1.85, 95% CI 0.57-6.05) AMD. The results did not change after adjustment for family history of AMD and cardiovascular disease. CONCLUSIONS: In this nested case-control sample of an older Australian population we found no association between C. pneumoniae antibody titers and early AMD. The study has insufficient power to assess an association with late AMD. PMID- 17724179 TI - Heritability and familial aggregation of refractive error in the Old Order Amish. AB - PURPOSE: To determine the heritability of refractive error and familial aggregation of myopia and hyperopia in an elderly Old Order Amish (OOA) population. METHODS: Nine hundred sixty-seven siblings (mean age, 64.2 years) in 269 families were recruited for the Amish Eye Study in the Lancaster County area of Pennsylvania. Refractive error was determined by noncycloplegic manifest refraction. Heritability of refractive error was estimated with multivariate linear regression as twice the residual sibling-sibling correlation after adjustment for age and gender. Logistic regression models were used to estimate the sibling recurrence odds ratio (OR(s)). Myopia and hyperopia were defined with five different thresholds. RESULTS: The age- and gender-adjusted heritability of refractive error was 70% (95% CI: 48%-92%) in the OOA. Age and gender-adjusted OR(s) and sibling recurrence risk (lambda(s)), with different thresholds defining myopia ranged from 3.03 (95% CI: 1.58-5.80) to 7.02 (95% CI: 3.41-14.46) and from 2.36 (95% CI: 1.65-3.19) to 5.61 (95% CI: 3.06-9.34). Age and gender-adjusted OR(s) and lambda(s) for different thresholds of hyperopia ranged from 2.31 (95% CI: 1.56-3.42) to 2.94 (95% CI: 2.04-4.22) and from 1.33 (95% CI: 1.22-1.43) to 1.85 (95% CI: 1.18-2.78), respectively. Women were significantly more likely than men to have hyperopia. There was no significant gender difference in the risk of myopia. CONCLUSIONS: In the OOA, refractive error is highly heritable. Hyperopia and myopia aggregate strongly in OOA families. PMID- 17724181 TI - A population-based epidemiological and genetic study of X-linked retinitis pigmentosa. AB - PURPOSE: To perform a nation-wide elucidation of the prevalence and the mutation spectrum in X-linked retinitis pigmentosa (XLRP), and to make genotype-phenotype comparisons. METHODS: The study comprised 96 affected males and 149 female carriers from 42 families representing all identified XLRP individuals in the Danish population (5.4 million inhabitants). RPGR and RP2 were screened for mutations in 34 families, the medical files of the patients were scrutinized, and phenotype data were extracted. RESULTS: The prevalence of affected males was estimated to be 1:26,200 and 1:18,000 of female carriers. A rough estimate, however, indicates that the real prevalence of affected males was approximately 1:15,000. The cumulated life risk of development of XLRP in carriers was strongly age dependent and included one third of the carriers older than 60 years. Molecular analysis of RP2 and RPGR uncovered 28 different mutations in 33 of 34 index cases analyzed. Twelve patients carried a mutation in RP2, 12 in exons 1 to 14, and 9 in open reading frame (ORF) 15 of RPGR. Males with RP2 mutations tended to have higher degrees of myopia, lower visual acuities, and more preserved visual fields than did males with RPGR mutations at the same age. No significant differences in phenotype were found in age of onset and type of mutation in either RP2 or RPGR. CONCLUSIONS: A very high mutation detection rate in familial cases makes genetic testing a valuable clinical tool for genetic counseling and prenatal testing. The proportion of RP2-mediated XLRP in the Danish population is higher and the proportion of RPGR-ORF15 is lower than reported in other studies. Thus, strategies for diagnostic procedures should take into account the population-specific mutation spectrum. PMID- 17724182 TI - Retinopathy in persons without diabetes: the Los Angeles Latino Eye Study. AB - PURPOSE: To assess the prevalence of retinopathy and its relationship to sociodemographic and clinical characteristics in a population-based cohort of adult Latinos without diabetes mellitus. METHODS: This was a population-based, cross-sectional study comprising 6357 Latinos, 40 years of age and older, from six census tracts in La Puente, Los Angeles, California. An interviewer administered questionnaire assessed sociodemographic factors and medical history. Color fundus photographs were taken and graded in a masked manner according to a modified Airlie House Classification Grading System. Participants underwent a physical examination that included height, weight, blood pressure, random serum glucose, and glycosylated hemoglobin measurements. Univariate and multivariate logistic regression analyses were used to assess associations between sociodemographic and clinical characteristics and retinopathy in persons without diabetes. RESULTS: The prevalence of retinopathy among individuals without diabetes in the Los Angeles Latino Eye Study (LALES) population was 6.6% (95% confidence interval 5.9%-7.4%). Stepwise logistic regression indicated that stage II hypertension (World Health Organization 2003 Guidelines), male gender, current smoking status, and obesity (body mass index >or= 30 kg/m(2)) were associated with retinopathy (odds ratio = 4.3, 1.6, 1.4, and 1.3, respectively). No statistically significant associations with retinopathy were present for Native American ancestry; country of origin; health insurance status; history of cardiovascular disease; or history of aspirin, oral contraceptive, or hormone replacement therapy. CONCLUSIONS: The data suggest that the prevalence of retinopathy in nondiabetic individuals among Latinos of primarily Mexican ancestry is significant. Independent risk indicators for retinopathy in the study population are hypertension, male gender, current smoking status, and obesity. PMID- 17724183 TI - Exposure to a controlled adverse environment impairs the ocular surface of subjects with minimally symptomatic dry eye. AB - PURPOSE: Adverse environmental conditions elicit dry eye (DE)-related signs and symptoms. The purpose of this work is to determine whether these conditions can alter a normal-to-borderline ocular surface in subjects with DE symptoms. METHODS: Ten minimally symptomatic contact lens (CL)-wearing subjects were exposed, without (WO-) and with (W-)CLs, to a controlled adverse environment (CAE) of 22.0 +/- 2.0 degrees C and 19.0% +/- 4.0% relative humidity (RH) for 2 hours in an environmental chamber (EC). One month later, the same subjects were placed in an indoor normal environment (INE) of 24.2 +/- 1.3 degrees C and 34.8% +/- 2.9% RH for 2 hours. DE-related signs and symptoms were evaluated before and after each exposure. The reversibility of changes provoked by CAE or INE was also evaluated. RESULTS: Without CL wear, significant changes were found in DE signs (noninvasive tear break-up time [NIBUT], conjunctival hyperemia and phenol red thread test) after CAE exposure, but not found after INE exposure. However with CL wear, the same tests were altered after both CAE and INE exposure. Most of these changes returned to normal values within 1 month after environmental exposure. CONCLUSIONS: Significant changes in comfort and the ocular surface tests were found after 2 hours of exposure to CAE. These results show the negative impact that an adverse environment, especially low RH, can have on the ocular surface. These alterations were fully reversible. This indicates that the CAE is a safe and functional condition in which to standardize DE diagnostic tests and evaluate therapeutics. PMID- 17724184 TI - Impulse activity in corneal sensory nerve fibers after photorefractive keratectomy. AB - PURPOSE: To evaluate the changes in spontaneous and stimulus-evoked nerve impulse activity of corneal polymodal and mechanonociceptor sensory fibers of the cornea after photorefractive keratectomy (PRK). METHODS: A central corneal ablation 6 mm in diameter and 70 microm in depth was performed with an excimer laser in both eyes of three anesthetized cats, after removal of the corneal epithelium. Single nerve fiber activity was recorded in these animals 12 to 48 hours after surgery. Activity in corneal nerve fibers with receptive fields (RFs) within and/or close to the wound, as well as with RFs far from the lesioned area, was studied. Incidence and frequency of spontaneous discharges and nerve impulse firing responses to mechanical (Cochet-Bonet esthesiometer) and chemical (CO(2) gas pulses) stimuli were studied. RESULTS: The incidence of nociceptor fibers exhibiting ongoing activity (15/35 vs. 1/9) and the frequency of their spontaneous firing (0.25 +/- 0.09 impulses [imp]/s versus 0.08 +/- 0.08 imp/s) was higher in fibers with RFs within and/or bordering the wounded area than in those with RFs far away from the wound. Mechanical responsiveness of fibers with RFs within or nearby the ablated area was often reduced. In these fibers, CO(2) pulses evoked a lower-frequency impulse discharge (0.9 +/- 0.2 imp/s inside, 2.3 +/- 0.7 imp/s outside the wound). CO(2)-evoked discharges recorded from fibers innervating the intact wound border were similar to those recorded in corneal fibers of intact cats. CONCLUSIONS: The spontaneous impulse activity and the abnormal responsiveness shown by a part of the corneal nerve fibers innervating the injured cornea are presumably the neurophysiological substrate of the pain sensations experienced by human patients hours after PRK surgery. PMID- 17724185 TI - Coated microneedles for drug delivery to the eye. AB - PURPOSE: To test the hypothesis that coated microneedles can deliver drugs into the eye via intrascleral and intracorneal routes in a minimally invasive manner. METHODS: Solid metal microneedles measuring 500 to 750 microm in length were coated with model drugs, protein, and DNA; inserted into nonpreserved human cadaveric sclera; and imaged. Microneedles coated with sodium fluorescein were then inserted into rabbit cornea in vivo. After needle removal, fluorescein concentration in the anterior segment of the rabbit eye was measured for 24 hours. Similar experiments were performed using pilocarpine-coated microneedles, and the rabbit pupil size was monitored afterward. RESULTS: In vitro insertion tests showed that microneedles were mechanically strong enough to penetrate into human cadaveric sclera and that the drug coating rapidly dissolved off the needles within the scleral tissue within 30 seconds after insertion. In vivo delivery from fluorescein-coated microneedles showed that fluorescein concentrations in the anterior chamber were 60 times greater than those achieved by topical application without microneedles. Similarly, microneedle delivery of pilocarpine caused rapid and extensive rabbit pupil constriction. There were no measurable inflammatory responses caused by microneedle insertion. CONCLUSIONS: This study demonstrated for the first time that coated microneedles can deliver drugs into the eye via intrascleral and intracorneal routes. This minimally invasive approach may avoid the complications associated with intraocular injection and systemic administration. PMID- 17724186 TI - Effect of allergic conjunctival inflammation on the allogeneic response to donor cornea. AB - PURPOSE: Immunologic rejection is the most common cause of corneal allograft rejection. Ipsilateral ocular inflammation has been identified as a predictor of future corneal graft failure. This study investigates the effect of perioperative allergic conjunctivitis on corneal allograft survival. METHODS: C57BL6 donor corneas were transplanted into naive A/J mice, A/J mice sensitized to short ragweed (SRW) pollen by intraperitoneal injection and then challenged with topical SRW to induce allergic conjunctivitis (Sens(+)Chall(+)), and A/J mice sensitized to SRW and challenged with topical PBS (Sens(+)Chall(-)). Syngeneic grafts were also performed in eyes with allergic conjunctivitis. Graft survival and infiltrating cell phenotype in rejected grafts were compared between groups. RESULTS: Mice with allergic conjunctivitis (Sens(+)Chall(+)) rejected corneal allografts significantly more quickly than naive mice. Syngeneic grafts in allergic eyes survived indefinitely. The rate of rejection in Sens(+)Chall(-) mice was similar to that in naive mice. There were no significant differences, between groups, in the numbers of infiltrating CD4(+) cells, CD8(+) cells, and macrophages at the time of graft rejection. Eosinophils were seldom observed in rejected grafts in naive and Sens(+)Chall(-) mice but were observed consistently in Sens(+)Chall(+) eyes. Eosinophils were also found consistently in the ciliary body of Sens(+)Chall(+) eyes at the time of graft rejection. CONCLUSIONS: Active allergic conjunctivitis at the time of transplantation accelerates corneal allograft rejection. Local conjunctival inflammation is an important factor in accelerating rejection. PMID- 17724188 TI - Postnatal corneal transparency, keratocyte cell cycle exit and expression of ALDH1A1. AB - PURPOSE: Recent studies have shown that rabbit corneal keratocytes abundantly express two water-soluble proteins, transketolase (TKT) and aldehyde dehydrogenase class 1A1 (ALDH1A1), in vivo and that these proteins may contribute to corneal transparency at the cellular level. The purpose of this study was to determine the relationship between the expression of these proteins and the development of postnatal corneal transparency. METHODS: Rabbits 1 day to 42 days of postnatal age were evaluated by in vivo confocal microscopy (CM) to measure corneal epithelial thickness, stromal thickness, and corneal haze. Selected corneas were then processed for immunocytochemistry and Western and Northern blot analyses, to determine stromal cell density, cell cycle entry, and expression of ALDH1A1 and TKT. RESULTS: Quantitative measurement of corneal haze showed that the postnatal cornea was hazy after birth and became transparent during the first weeks after eyelid opening. Development of transparency was associated with decreased cytoplasmic light-scattering from postnatal corneal stromal cells, with the appearance of nuclear light-scattering after eyelid opening. Four days after birth, stromal cell density decreased rapidly, and the cells became quiescent, showing decreased staining by Ki67, a cell cycle marker. Whereas expression of TKT showed a gradual increase after birth, ALDH1A1 showed a marked increase after eyelid opening, and the combined expression significantly correlated with the reduction in light-scattering by postnatal stromal cells. CONCLUSIONS: The data suggest that development of postnatal corneal transparency is associated with decreased keratocyte density and quiescence and the expression of TKT/ALDH1A1. PMID- 17724189 TI - Validation study of VEP vernier acuity in normal-vision and amblyopic adults. AB - PURPOSE: Vernier displacement thresholds can be measured with swept-parameter visual evoked potentials (sVEPs) and may therefore be useful in pre- or nonverbal subjects. This study was conducted to test whether sVEP vernier thresholds are valid measures of the visibility of vernier offsets in two different settings. METHODS: Vernier acuity thresholds were measured psychophysically and electrophysiologically using square-wave gratings containing vernier displacements modulated at 3.76 Hz. The detectability of the vernier alignment cue was degraded by introducing either gaps or standing offsets in the stimulus. These manipulations were performed in normal-vision observers. In a second experiment, psychophysical and sVEP vernier acuity were measured in amblyopic observers. RESULTS: sVEP thresholds and overall amplitudes in normal observers were strongly affected by the introduction of gaps or standing offsets, as were psychophysical thresholds. Psychophysical and sVEP vernier offset thresholds were significantly correlated in the amblyopic eyes, as were sVEP and optotype interocular threshold differences. sVEP amplitudes of patients with strabismus were lower than those of patients with anisometropic amblyopia, even though optotype acuities were the same in the two groups. CONCLUSIONS: Vernier acuity thresholds derived from the sVEP tap mechanisms that are specific for the relative position of stimulus elements, and they correlate with perceptual visibility in normal and amblyopic observers. Because of this correlation and because sVEP thresholds can be measured without the need for instruction or behavioral responses, they may be useful in assessing visual function in pre- and nonverbal patients. PMID- 17724187 TI - Morphologic characterization of organized extracellular matrix deposition by ascorbic acid-stimulated human corneal fibroblasts. AB - PURPOSE: To characterize the structure and morphology of extracellular matrix (ECM) synthesized by untransformed, cultured human corneal fibroblasts in long term cultures. METHODS: Human corneal stromal keratocytes were expanded in transwell culture in the presence of fetal bovine serum and a stable derivative of vitamin C. The cells were allowed to synthesize a fibrillar ECM for up to 5 weeks. Constructs were assessed by light (phase-contrast and differential interference-contrast) and transmission (standard and quick freeze/deep etch) microscopy. RESULTS: Electron micrographs revealed stratified constructs with multiple parallel layers of cells and an extracellular matrix comprising parallel arrays of small, polydisperse fibrils (27-51 nm) that often alternate in direction. Differential interference contrast images demonstrated oriented ECM fibril arrays parallel to the plane of the construct, whereas quick-freeze, deep etch micrographs showed the details of the matrix interaction with fibroblasts through arrays of membrane surface structures. CONCLUSIONS: Human keratocytes, cultured in a stable vitamin C derivative, are capable of assembling extracellular matrix, which comprises parallel arrays of ECM fibrils. The resultant constructs, which are highly cellular, are morphologically similar to the developing mammalian stroma, where organized matrix is derived. The appearance of arrays of structures on the cell membranes suggests a role in the local organization of synthesized ECM. This model could provide critical insight into the fundamental processes that govern the genesis of organized connective tissues such as the cornea and may provide a scaffolding suitable for tissue engineering a biomimetic stroma. PMID- 17724190 TI - Reduction of inner retinal thickness in patients with autosomal dominant optic atrophy associated with OPA1 mutations. AB - PURPOSE: To determine the morphologic changes in the retina in the macula and around the optic disc in patients with autosomal dominant optic atrophy (ADOA) associated with a mutation in the OPA1 gene. METHODS: Cross-sectional images of the macular area of the retina were obtained by optical coherence tomography (OCT) in patients with ADOA who had a heterozygous mutation in the OPA1 gene. There were 15 eyes of eight patients from five families: four men and four women. The average age of the patients was 48.1 years. In the OCT images, the cross sections of the sensory retina were divided manually into four areas. The thickness of the overall sensory retina and the divided areas were measured at 1 and 2 mm on the temporal, nasal, superior, and inferior sides of the fovea as well as at the fovea. The thickness of the retinal nerve fiber layer (RNFL) around the optic discs was measured by taking circular scans (3.4 mm in diameter) centered on the optic disc. The results in the patients with ADOA were compared with those from 11 normal control subjects. RESULTS: The overall thickness of the sensory retina in the macular area was significantly thinner in the patients with ADOA than in the control subjects at all points except the fovea (P < 0.0001). The RNFL in the macular area in the patients with ADOA was significantly thinner than that in control subjects at all points (P < 0.0001), especially at 1 mm from the fovea. The circumpapillary RNFL was significantly thinner at the temporal, superior, and inferior areas in patients with ADOA but not in the nasal area. The total cross-sectional area of the circumpapillary RNFL was significantly correlated with visual acuity. The thickness of the combined ganglion cell layer, inner plexiform layer, inner nuclear layer, and outer plexiform layer in the macular area was significantly thinner in the patients (P < 0.0056). The thickness of the outer nuclear layer and the photoreceptor inner segments and the thickness of the photoreceptor outer segments were not significantly different between the patients with ADOA and normal control subjects. CONCLUSIONS: The RNFL and the layer including the ganglion cell layer are significantly thinner in patients with ADOA associated with an OPA1 gene mutation, whereas the photoreceptor layers are not affected morphologically. The inner retina is the main area of the retina altered in ADOA. PMID- 17724191 TI - Optic disc evaluation by optical coherence tomography in nonarteritic anterior ischemic optic neuropathy. AB - PURPOSE: To describe the characteristics of the optic nerve head (ONH) in patients with nonarteritic anterior ischemic optic neuropathy (NAION) and compare them with control subjects by using optical coherence tomography (OCT). METHODS: Patients with NAION underwent a complete ophthalmic examination, including OCT scanning of the ONH at diagnosis. The examination was repeated 1.5, 3, and 6 months later. Age- and sex-matched control subjects with no ocular disease underwent a similar evaluation. Data were obtained by using the ONH analysis protocol of the StratusOCT (Carl Zeiss Meditec, Dublin, CA). RESULTS: Twenty three patients and 23 control subjects were included. In eyes with NAION, the vertical integrated rim area decreased significantly (P < 0.01) from the acute phase to the 6-month visit. The cup-to-disc (C/D) area ratio increased significantly (P = 0.002) from the acute examination to the 3-month visit. There was a significant difference between the NAION fellow eyes and the control eyes in C/D ratio, evaluated by slit lamp funduscopy (P < 0.001), and in the C/D area ratio (P = 0.001). The vertical integrated rim area was significantly (P = 0.001) greater in NAION fellow eyes than in control eyes. There was no significant difference in optic disc area or vertical disc diameter among the control eyes, NAION-affected eyes, and NAION fellow eyes. CONCLUSIONS: Although patients with NAION have lower C/D ratios than does the normal population, with a higher level of nerve fiber crowding, there was no difference in optic disc size between patients with NAION and control subjects. After the development of NAION, 47.8% of eyes had a C/D ratio that differed from that in the fellow eye by more than 0.1. PMID- 17724192 TI - Acuity development in infantile nystagmus. AB - PURPOSE: To compare development of acuity in patients with isolated infantile nystagmus and infantile nystagmus associated with a visual sensory defect. METHODS: Visual acuities in 57 children (1 month to 4 years of age) with infantile nystagmus were assessed by using Teller acuity cards oriented vertically during binocular viewing. Twenty-two had isolated infantile nystagmus, 21 had albinism, 7 had aniridia, and 7 had mild or moderate bilateral optic nerve hypoplasia (BONH). Longitudinal acuity was measured in 40 of these patients (mean 1.8, 2.3, 3.1, and 3.3, measurements per patient group, respectively). The rate of acuity development across the study groups was quantified by linear regression of log acuity versus log age and compared to published normative data. RESULTS: The rate of acuity development was similar across all groups and paralleled the normative data. The slope of log grating acuity versus log age (+/-SEM) was normal, 0.73; isolated infantile nystagmus, 0.80 +/- 0.11; albinism, 0.80 +/- 0.11; aniridia, 0.87 +/- 0.16; and BONH, 0.79 +/- 0.18. The slopes were not significantly different (ANCOVA, F(4,142) = 0.21, P = 0.93). Compared with published binocular normative data, mean acuity adjusted for age was reduced by 1.2 octaves in isolated infantile nystagmus and by 1.7 to 2.5 octaves in nystagmus with associated sensory defect. CONCLUSIONS: The rate of acuity development in infantile nystagmus is largely independent of the gaze-holding instability or an associated visual sensory defect. Reduction of mean acuity in albinism, aniridia, and BONH is due to the visual sensory defect and exceeds the acuity reduction observed in isolated infantile nystagmus. PMID- 17724193 TI - The British Infantile and Childhood Glaucoma (BIG) Eye Study. AB - PURPOSE: Pediatric glaucoma is a rare, potentially blinding condition, yet, in the United Kingdom, there is a paucity of contemporary epidemiologic and clinical data regarding this condition. The British Infantile and Childhood Glaucoma (BIG) Eye Study is the first national population-based study conducted to examine the incidence, detection patterns, current management, and intraocular pressure (IOP) control at 1 year in children with newly diagnosed glaucoma in the United Kingdom. METHODS: A prospective study was conducted wherein children in the United Kingdom and Republic of Ireland aged 0.80) when compared with untreated baseline values or vehicle-treated control eyes. CONCLUSIONS: The reduction in IOP produced by 0.001% KL was equivalent to, and at some measured time points, greater than the effect produced by 0.005% latanoprost. The IOP reduction by KL in normal monkeys appeared to have no effect on aqueous humor production or tonographic outflow facility and may thus indicate a drug-induced increase in uveoscleral outflow. PMID- 17724200 TI - Expression of indoleamine 2,3-dioxygenase in human corneal cells as a local immunosuppressive factor. AB - PURPOSE: To identify the localization of indoleamine 2,3-dioxygenase (IDO) in human corneal cells and to evaluate its functional ability as a local immunosuppressive factor. METHODS: The expression profile of IDO was identified in primary cultures of human corneal cells (fibroblasts, epithelial cells, endothelial cells) by RT-PCR and Western blot analysis. The immunosuppressive function of IDO was assessed by culturing human CD4(+) T cells with conditioned medium derived from the three types of human corneal cells, and changes in proliferation and apoptosis were determined. IDO expression and its apoptotic effects on CD4(+) T cells were also investigated after IFN-gamma treatment. RESULTS: Among the three types of human corneal cells, IDO mRNA and protein expression were observed in human corneal fibroblasts and epithelial cells, with higher levels in the human corneal fibroblasts. Human CD4(+) T cells cultivated in conditioned medium derived from human corneal fibroblasts showed decreased cell proliferation and increased apoptosis. IFN-gamma treatment significantly induced IDO expression and showed apoptotic effects on immune cells. CONCLUSIONS: These results suggest that human corneal fibroblasts are relatively immunoresistant and that the IDO expression can act as one of the factors for the maintenance of immune privilege in the cornea. PMID- 17724201 TI - Characterization of IL-17+ interphotoreceptor retinoid-binding protein-specific T cells in experimental autoimmune uveitis. AB - PURPOSE: The aims of this study were to determine whether IL-17(+) T cells were present in CD4 and CD8 interphotoreceptor retinoid-binding protein (IRBP) specific T cells and to determine the role of antigen-specific and nonspecific IL 17(+) T cells in the pathogenesis of experimental autoimmune uveitis (EAU). METHODS: B6 mice were immunized with uveitogenic peptide IRBP1-20. In vivo-primed T cells were separated and stimulated with the immunizing peptide. Intracellular expression of IFN-gamma and IL-17 by the T cells was assessed, and the pathogenic activity of the activated T cells was determined. RESULTS: A subset of autoreactive IRBP-specific CD8 T cells expressed IL-17. IRBP-specific T cells preferentially expressed IL-17 when expanded by IL-23, whereas IFN-gamma expressing cells were dominant when the T cells were cultured with IL-2. Importantly, both expanded T-cell populations were uveitogenic. In addition, IL 23 promoted the expansion of antigen-specific and non-antigen-specific IL-17(+) T cells, whereas TGF-beta and IL-6 acted only on non-antigen-specific IL-17(+) T cells. Only the antigen-specific IL-17(+) T cells were uveitogenic. The activation of autoreactive IL-17(+) T cells was markedly increased in vivo by the mycobacterial component of CFA and pertussis toxin (PTX) and in vitro by the ligation of Toll-like receptors. CONCLUSIONS: IL-17(+) T cells can be readily detected among activated autoreactive and bystander T cells and may play a major role in the pathogenesis of EAU. PMID- 17724202 TI - Effects of CXCR3 signaling on development of fatal encephalitis and corneal and periocular skin disease in HSV-infected mice are mouse-strain dependent. AB - PURPOSE: The host inflammatory response to ocular infection with herpes simplex virus (HSV) can be either protective, with disease-free survival, or it can promote diseases such as HSV corneal disease (or herpes stromal keratitis [HSK] in humans) and encephalitis (HSE), depending on mouse strain. The role of CXCR3 chemokine signaling in HSV-induced central nervous system (CNS) inflammation and corneal disease was evaluated, and responses in genetically susceptible and resistant strains of mice were contrasted. METHODS: Resistant C57BL/6J (B6) and susceptible 129S6 (129) mice were given monoclonal antibodies (mAbs) to neutralize the CXCR3 ligands monokine induced by interferon-gamma (MIG, CXCL9) and interferon inducible protein-10 (IP-10, CXCL10) during HSV infection. In addition, the development of HSV disease was monitored in CXCR3-null mutant mice derived from resistant (B6) and susceptible (BALB/c) strains. Inflammatory cells infiltrating the cornea and brain stem were isolated and stained for flow cytometric analysis. RESULTS: MIG and IP-10 were induced in nervous system tissue after HSV inoculation by the corneal route. HSV-infected 129 mice treated with MIG- or IP-10-neutralizing mAbs showed significantly enhanced survival compared with mice treated with control isotype antibody, whereas survival of the B6 mice was unaltered. Similarly, greater survival was observed for BALB.CXCR3(-/-) mice compared with control BALB/c mice. Reduced CNS inflammation was documented that extended to the cornea, such that HSV corneal disease severity was reduced in susceptible BALB.CXCR3(-/-). In contrast, although survival of B6 and B6.CXCR3(-/ ) mice was indistinguishable, B6.CXCR3(-/-) mice developed more severe corneal and periocular skin disease. CONCLUSIONS: The effects of CXCR3 signaling in HSV infection are strongly dependent on mouse strain. PMID- 17724203 TI - Efficacy of topical immunoglobulins against experimental adenoviral ocular infection. AB - PURPOSE: Presently, there is no U.S. Federal Drug Administration (FDA)-approved antiviral therapy for the treatment of adenoviral (Ad) ocular infections. The goal of the present study was to determine the antiviral efficacy of human immunoglobulin (Ig), a preparation of highly purified and concentrated immunoglobulin (IgG) antibodies isolated from a large pool of human plasma donors, in vitro and on acute Ad replication in the Ad5 New Zealand White (NZW) rabbit ocular model. METHODS: The antiviral activity of human Ig against multiple wild-type and human ocular isolates of adenovirus serotypes was investigated in vitro by using neutralizing assays in different human epithelial cell lines. In vivo bilateral topical ocular toxicity and antiviral efficacy were evaluated with established Ad5/NZW rabbit ocular models. In vivo Ig antiviral results were compared with those obtained with topical 0.5% cidofovir and saline. RESULTS: In three different epithelial cell lines, 0.05). The response amplitude of accommodation during facility tasks was found to be similar in the two refractive groups. However, the velocity of accommodation was found to be lower in myopes than in emmetropes for distance facility (P < 0.05) but not for near facility (P > 0.05). Velocity of disaccommodation was lower in myopes than in emmetropes at both distance and near (P < 0.05). CONCLUSIONS: During distance accommodative facility testing, myopes exhibited a lower velocity of accommodation and disaccommodation, which led to a lower distance accommodative facility rate. For near facility measurements, however, although velocity of disaccommodation was lower in myopes, velocity of accommodation was found to be similar in the two refractive groups. A variety of factors that contribute to these differences are discussed. PMID- 17724231 TI - Anti endothelial cell antibodies in vasculitis. PMID- 17724232 TI - Resolved: capillary endothelium is a major contributor to the glomerular filtration barrier. AB - There is growing debate as to the primal role of capillary endothelial cells in the barrier function of the glomerular filter. Two experts argue the points for and against. Clearly unresolved is agreement whether glomerular capillary endothelium has fenestrae subtended by diaphragms. PMID- 17724233 TI - Quality improvement or research? The ethics of hospital project oversight. PMID- 17724234 TI - Study's suggestion for oxygen saturation risks blinding neonates. PMID- 17724235 TI - Use of AEGs not rare everywhere. PMID- 17724236 TI - Nurse residency programs are a necessary investment. PMID- 17724237 TI - An Italian perspective on family presence. PMID- 17724238 TI - Exploration of power imbalances and communication are key. PMID- 17724240 TI - Decisions made by critical care nurses during mechanical ventilation and weaning in an Australian intensive care unit. AB - BACKGROUND: Responsibilities of critical care nurses for management of mechanical ventilation may differ among countries. Organizational interventions, including weaning protocols, may have a variable impact in settings that differ in nursing autonomy and interdisciplinary collaboration. OBJECTIVE: To characterize the role of Australian critical care nurses in the management of mechanical ventilation. METHODS: A 3-month, prospective cohort study was performed. All clinical decisions related to mechanical ventilation in a 24-bed, combined medical surgical adult intensive care unit at the Royal Melbourne Hospital, a university affiliated teaching hospital in Melbourne, Victoria, Australia, were determined. RESULTS: Of 474 patients admitted during the 81-day study period, 319 (67%) received mechanical ventilation. Death occurred in 12.5% (40/319) of patients. Median durations of mechanical ventilation and intensive care stay were 0.9 and 1.9 days, respectively. A total of 3986 ventilation and weaning decisions (defined as any adjustment to ventilator settings, including mode change; rate or pressure support adjustment; and titration of tidal volume, positive end expiratory pressure, or fraction of inspired oxygen) were made. Of these, 2538 decisions (64%) were made by nurses alone, 693 (17%) by medical staff, and 755 (19%) by nurses and staff in collaboration. Decisions made exclusively by nurses were less common for patients with predominantly respiratory disease or multiple organ dysfunction than for other patients. CONCLUSIONS: In this unit, critical care nurses have high levels of responsibility for, and autonomy in, the management of mechanical ventilation and weaning. Revalidation of protocols for ventilation practices in other clinical contexts may be needed. PMID- 17724241 TI - Evidence-based review and discussion points. PMID- 17724242 TI - Chronically critically ill patients: health-related quality of life and resource use after a disease management intervention. AB - BACKGROUND: Chronically critically ill patients often have high costs of care and poor outcomes and thus might benefit from a disease management program. OBJECTIVES: To evaluate how adding a disease management program to the usual care system affects outcomes after discharge from the hospital (mortality, health related quality of life, resource use) in chronically critically ill patients. METHODS: In a prospective experimental design, 335 intensive care patients who received more than 3 days of mechanical ventilation at a university medical center were recruited. For 8 weeks after discharge, advanced practice nurses provided an intervention that focused on case management and interdisciplinary communication to patients in the experimental group. RESULTS: A total of 74.0% of the patients survived and completed the study. Significant predictors of death were age (P = .001), duration of mechanical ventilation (P = .001), and history of diabetes (P = .04). The disease management program did not have a significant impact on health-related quality of life; however, a greater percentage of patients in the experimental group than in the control group had "improved" physical health-related quality of life at the end of the intervention period (P = .02). The only significant effect of the intervention was a reduction in the number of days of hospital readmission and thus a reduction in charges associated with readmission. CONCLUSION: The intervention was not associated with significant changes in any outcomes other than duration of readmission, but the supportive care coordination program could be provided without increasing overall charges. PMID- 17724243 TI - Types of intensive care units with the healthiest, most productive work environments. AB - BACKGROUND: The quality of nurses' work environments in hospitals is of great concern. The American Association of Critical-Care Nurses has specified 6 standards essential to a healthy (ie, satisfying and productive) work environment. These standards are sufficiently aligned to the Essentials of Magnetism processes to make this tool suitable for measuring healthy work environments. OBJECTIVES: To identify differences in staff nurses' perceptions of the work environment by type of intensive care unit. METHODS: A cross-sectional descriptive design with strategic sampling was used in this secondary analysis of data from 698 staff nurses working in 34 intensive care units in 8 magnet hospitals. Intensive care units were grouped into 4 types: medical, including coronary care; surgical, including trauma and cardiovascular; neonatal and pediatric; and medical-surgical. All nurses completed the Essentials of Magnetism instrument. Analysis of variance was used to identify initial differences; multivariate analysis of variance was used to control for covariates. RESULTS: The intensive care nurses and units scored above the National Magnet Hospital Profile mean on process variables and on the Essentials of Magnetism outcome variables. Neonatal and pediatric units scored significantly higher than did the other types of intensive care units sampled. CONCLUSIONS: Intensive care unit structures supported care processes and relationships that resulted in job satisfaction among nurses and high-quality care for patients in this strategic sample. Systematic study of the structures and processes present in units reporting a healthy work environment can be used to assist other clinical units in improving work environments. PMID- 17724244 TI - Understanding collaboration between nurses and physicians as knowledge at work. AB - BACKGROUND: Collaboration between nurses and physicians is linked to positive outcomes for patients, especially in the intensive care unit. However, effective collaboration poses challenges because of traditional barriers such as sex and class differences, hierarchical organizational structures in health-care, and physicians' belief that they are the final arbiter of clinical decisions. OBJECTIVE: To further analyze the results of an investigation on how intensive care unit culture, expressed through everyday practices, affected the care of patients who became confused. METHODS: A model of the types of knowledge (case, patient, and person) used in clinical work was used to analyze the breakdown in collaboration detected in the original study. RESULTS: Breakdown of collaboration occurred because of the types of knowledge used by physicians and nurses. Certain types of knowledge were privileged even when not applicable to the clinical problem, whereas other types were dismissed even when applicable. CONCLUSION: Viewing collaboration through the conceptual lens of knowledge use reveals new insights. Collaboration broke down in the specific context of caring for patients with confusion because the use of case knowledge, rather than patient knowledge, was prominent in the intensive care unit culture. PMID- 17724245 TI - Role of nurses in a university hospital during mass casualty events. AB - Mass casualty events due to terror attacks have escalated throughout Israel since September 2000, with a high proportion of these events occurring in the Jerusalem area. Immediately after news of a large-scale terror attack is received, family/public information centers are set up in all local hospitals to meet the needs of members of the public who call or arrive at hospitals anxious to obtain information about relatives who may have been at the site of the attack. The most urgent task facing these centers is the quick and accurate identification of victims whose identity is in question. To date, some 3000 casualties have been treated at Hadassah Hebrew University Medical Center (Hadassah), a level I trauma center. This number accounts for nearly half of Israel's total number of casualties from terror attacks during this period. Extensive experience has led the hospital to develop a unique organizational model for its family/public information center; in this model, members of the nursing staff identify casualties. The experience and knowledge gained in dealing with terror events also can be applied to other types of mass casualty events, such as major road or work accidents. PMID- 17724246 TI - Accuracy and precision of noninvasive temperature measurement in adult intensive care patients. AB - BACKGROUND: Research on the accuracy and precision of noninvasive methods of measuring body temperature is equivocal. OBJECTIVES: To determine accuracy and precision of oral, ear-based, temporal artery, and axillary temperature measurements compared with pulmonary artery temperature. METHODS: Repeated measures design conducted for 6 months. Sequential temperature measurements on the same side of the body were obtained within 1 minute, with measurements repeated 3 times at 20-minute intervals. Accuracy, precision, and confidence limits were analyzed. RESULTS: In 60 adults with cardiopulmonary disease and a pulmonary artery catheter, mean pulmonary artery temperature was 37.1 degrees C (SD 0.6 degrees C, range 35.3 degrees C-39.4 degrees C). Mean (SD) offset from pulmonary artery temperature (with the mean reflecting accuracy and SD reflecting precision) and confidence limits were 0.09 degrees C (0.43 degrees C) and -0.75 degrees C to 0.93 degrees C for oral measurements, -0.36 degrees C (0.56 degrees C) and -1.46 degrees C to 0.74 degrees C for ear measurements, -0.02 degrees C (0.47 degrees C) and -0.92 degrees C to 0.88 degrees C for temporal artery measurements, and 0.23 degrees C (0.44 degrees C) and -0.64 degrees C to 1.12 degrees C for axillary measurements. Percentage of pairs with differences greater than +/-0.5 degrees C was 19% for oral, 49% for ear, 20% for temporal artery, and 27% for axillary measurements. Intubation increased oral measurements compared with pulmonary artery temperatures (mean difference 0.3 degrees C, SD 0.3 degrees C, P = .001). CONCLUSIONS: Oral and temporal artery measurements were most accurate and precise. Axillary measurements underestimated pulmonary artery temperature. Ear measurements were least accurate and precise. Intubation affected the accuracy of oral measurements; diaphoresis and airflow across the face may affect temporal artery measurements. PMID- 17724247 TI - Hyperinsulinemic euglycemia therapy for verapamil poisoning: a review. AB - Treatment of patients with verapamil overdose remains challenging. Traditional decontamination and supportive measures with intravenous calcium and vasopressors are the mainstays in initial care. Recently, the successful use of rescue hyperinsulinemic euglycemia therapy has been described in multiple cases. Treatment resulted in improved hemodynamic parameters and increased metabolic efficiency in patients with a low-output, myocardial shock state. Information on clinical use of hyperinsulinemic euglycemia therapy in humans is limited to case reports and small case series; no controlled clinical trials have been done. Hyperinsulinemic euglycemia therapy should be considered for patients with calcium channel blocker overdose who do not respond to initial supportive therapy. PMID- 17724248 TI - Simulation and the teaching and learning of practice in critical care units. PMID- 17724249 TI - His electrograms in the interpretation of cardiac arrhythmias. PMID- 17724250 TI - ECG marker of nontransmural myocardial infarction. PMID- 17724251 TI - Hyperinsulinemic euglycemia therapy for verapamil poisoning: case report. AB - A 49-year-old woman was brought to the emergency department because of an intentional overdose of sustained-release verapamil along with captopril and glyburide. The estimated interval between ingestion and the time she was found was several hours. Initial findings were blood pressure 72/39 mm Hg, heart rate 32/min, and a score of 9 on the Glasgow Coma Scale. She was intubated and given intravenous fluid and vasopressor support. Decontamination with activated charcoal was instituted. Administration of dopamine and norepinephrine, atropine, sodium bicarbonate, and calcium chloride did not yield significant clinical improvement. Hyperinsulinemic euglycemia therapy was started: a bolus of regular insulin then infusions of insulin and 10% dextrose. After 24 hours of therapy, the bradycardia resolved and the patient's hemodynamic condition stabilized with normalization of cardiac indices. On day 5 the patient was transferred to the medical unit, and on day 8 she was discharged to psychiatric care. PMID- 17724253 TI - Acetaminophen inhibits prostanoid synthesis by scavenging the PGHS-activator peroxynitrite. AB - The primary pharmacological target of acetaminophen is prostaglandin endoperoxide H2 synthase (PGHS). The enzymatic catalytic mechanism is radical-based, initiated, and maintained by the persistent presence of peroxides, particularly peroxynitrite, which is termed "peroxide tone". Whereas the prevailing concept assumes a direct reduction of the active, oxidized enzyme by acetaminophen, here we show that acetaminophen is a potent scavenger of peroxynitrite (peroxynitrite mediated phenol nitration, IC50 approximately 72 microM; Sin-1-mediated DHR123 oxidation, IC50 approximately 11 microM) and thus inhibits PGHS by eliminating the peroxide tone. Nanomolar concentrations of peroxynitrite increased the activity of isolated PGHS and prostacyclin formation by aortic endothelial cells. This elevated activity was efficiently inhibited by pharmacologically relevant concentrations of acetaminophen (IC50 approximately 10 microM for 6-keto PGF1alpha) and other free radical scavengers. However, when the peroxide tone was provided by H2O2 or tert-butyl-OOH, acetaminophen had only negligible inhibitory effects. Our concept could help to explain the efficacy of acetaminophen to inhibit PGHS in cell types with moderate oxidant formation. However, high levels of peroxynitrite or other peroxides such as lipid peroxides formed at inflammatory sites might overwhelm the ability of acetaminophen to decrease PGHS activation. The concept presented herein provides a molecular basis to explain the excellent analgesic and antipyretic properties of acetaminophen together with its minimal anti-inflammatory effects. PMID- 17724252 TI - Cot, a novel kinase of histone H3, induces cellular transformation through up regulation of c-fos transcriptional activity. AB - Post-translational modification of histones is critical for gene expression, mitosis, cell growth, apoptosis, and cancer development. Thus, finding protein kinases that are responsible for the phosphorylation of histones at critical sites is considered an important step in understanding the process of histone modification. The serine/threonine kinase Cot is a member of the mitogen activated protein kinase (MAPK) kinase kinase family. We show here that Cot can phosphorylate histone H3 at Ser-10 in vivo and in vitro, and that the phosphorylation of histone H3 at Ser-10 is required for Cot-induced cell transformation. We found that activated Cot is recruited to the c-fos promoter resulting in increased activator protein-1 (AP-1) transactivation. The formation of the Cot-c-fos promoter complex was also apparent when histone H3 was phosphorylated at Ser-10. Furthermore, the use of dominant negative mutants of histone H3 revealed that Cot was required for phosphorylation of histone H3 at Ser-10 to induce neoplastic cell transformation. These results revealed an important function of Cot as a newly discovered histone H3 kinase. Moreover, the transforming ability of Cot results from the coordinated activation of histone H3, which ultimately converges on the regulation of the transcriptional activity of the c-fos promoter, followed by AP-1 transactivation activity. PMID- 17724254 TI - Anxiety predicts mortality and morbidity after coronary artery and valve surgery- a 4-year follow-up study. AB - OBJECTIVE: To explore the long-term effect of anxiety and depression on outcome after cardiac surgery. To date, the relationship between psychosocial factors and future cardiac events has been investigated mainly in population-based studies, in patients after cardiac catheterization or myocardial infarction. METHODS: In total, 180 patients who underwent cardiac surgery using cardiopulmonary bypass were prospectively studied and followed up for 4 years. Anxiety (Spielberger State-Trait Anxiety Inventory, STAI-S/STAI-T), depression (Beck Depression Inventory, BDI), living alone, and education level along with clinical risk factors and perioperative characteristics were assessed. Psychological self report questionnaires were completed preoperatively and 6, 12, 24, 36, and 48 months after discharge. Clinical end-points were mortality and cardiac events requiring hospitalization during follow-up. RESULTS: Average preoperative STAI-T score was 44.6 +/- 10. Kaplan-Meier analysis showed a significant effect of preoperative STAI-T >45 points (p = .008) on mortality. In multivariate models, postoperative congestive heart failure (OR: 10.8; 95% confidence interval [CI]: 2.9-40.1; p = .009) and preoperative STAI-T (score OR: 1.07; 95% CI: 1.01-1.15; p = .05) were independently associated with mortality. The occurrence of cardiovascular hospitalization was independently associated with postoperative intensive care unit days (OR: 1.41; 95% CI: 1.01-1.96; p = .045) and post discharge 6th month STAI-T (OR: 1.06; 95% CI:1.01-1.13; p = .03). CONCLUSIONS: The results of the present study suggest that the assessment of psychosocial factors, particularly the ongoing assessment of anxiety, could help in risk stratification and identification of patients at risk of mortality and cardiovascular morbidity after cardiac surgery. PMID- 17724255 TI - Association between physical fitness, parasympathetic control, and proinflammatory responses to mental stress. AB - OBJECTIVES: To examine the association between physical fitness, cardiac parasympathetic control, and inflammatory cytokine responses to mental stress. Exercise and physical fitness may act as a buffer to the detrimental effects of psychosocial stress exposure. METHODS: Participants were 207 men and women (52 +/ 3 years) drawn from the Whitehall II epidemiological cohort. Participants completed two mental stressors consisting of a 5-minute Stroop task and a 5 minute mirror tracing task. Blood samples were obtained during baseline and 45 minutes post stress. Heart rate variability (HRV) was measured during baseline, stress, and recovery. Physical fitness was assessed from a submaximal exercise test. RESULTS: Interleukin (IL)-6 and IL-1 receptor antagonist were increased significantly at 45 minutes post stress. Multiple linear regression analysis, adjusted for age, body mass index, gender, smoking, alcohol, grade of employment, and basal levels of inflammatory markers demonstrated that exercise heart rate (a fitness indicator) was related to IL-6 (beta = 0.24; p = .005) and tumor necrosis factor (TNF)-alpha responses to stress (beta = 0.27; p = .002). Exercise heart rate was also related to the HRV response to stress (beta = -0.23; p = .02). A higher systolic blood pressure response to exercise was a predictor of TNF-alpha responses to stress (beta = 0.18; p = .03). CONCLUSIONS: Physical fitness (as indexed by lower exercise heart rate) is associated with smaller inflammatory cytokine responses to acute mental stress, an effect that may be partly mediated through parasympathetic pathways. This may be one of the mechanisms by which physical fitness confers protection against cardiovascular risk. PMID- 17724257 TI - Disseminating cardiopulmonary resuscitation training by distributing 35,000 personal manikins among school children. AB - BACKGROUND: Because most cardiac arrests occur at home, widespread training is needed to increase the incidence of cardiopulmonary resuscitation (CPR) by lay persons. The aim of this study was to evaluate the effect of mass distribution of CPR instructional materials among schoolchildren. METHODS AND RESULTS: We distributed 35,002 resuscitation manikins to pupils (12 to 14 years of age) at 806 primary schools. Using the enclosed 24-minute instructional DVD, they trained in CPR and subsequently used the kit to train family and friends (second tier). They completed a questionnaire on who had trained in CPR using the kit. Teachers also were asked to evaluate the project. The incidence of bystander CPR in out-of hospital cardiac arrest in the months following the project was compared with the previous year. In total, 6947 questionnaires (19.8%) were returned. The 6947 kits had been used to train 17,140 from the second tier (mean, 2.5 persons per pupil; 95% confidence interval, 2.4 to 2.5). The teachers had used a mean of 64 minutes (95% confidence interval, 60 to 68) for preparation and a mean of 13 minutes (95% confidence interval, 11 to 15) to tidy up. Incidence of bystander CPR in the months after the project did not increase significantly compared with the previous year (25.0% versus 27.9%; P=0.16). CONCLUSIONS: CPR training can be disseminated in a population by distributing personal resuscitation manikins among children in primary schools. The teachers felt able to easily facilitate CPR training. The incidence of bystander CPR did not increase significantly in the months following the project. PMID- 17724256 TI - Attachment anxiety, relationship context, and sleep in women with recurrent major depression. AB - OBJECTIVE: To examine the relationship between attachment anxiety, marital status, bed-partner status, and sleep in recurrently depressed women. METHODS: The current study measured polysomnography (PSG) and subjective sleep quality in 107 women with recurrent major depression. Women were categorized as high or low in attachment anxiety based on Bartholomew and Horowitz's Relationship Questionnaire (1991). RESULTS: There were no significant main or interaction effects of any of the relationship measures on subjective sleep quality. In contrast, PSG results indicated that women with bed partners displayed better sleep efficiency (p < .005). Marital status was also associated with sleep efficiency (p < .05), and married women displayed significantly shorter sleep latencies as compared with never married women (p < .05). Anxiously attached women displayed a reduced percentage of stage 3-4 sleep (p < .05). Moreover, a significant interaction between attachment anxiety and marital status (p < .05) suggested that anxiously attached women who were previously married (i.e., divorced, separated, or widowed) displayed a particularly low percentage of stage 3-4 sleep. CONCLUSIONS: Depressed women who exhibit an anxious attachment style and have experienced a marital rupture show reduced stage 3-4 sleep, which may signal a concomitant reduction in restorative cognitive and metabolic processes. Relationship context influences sleep continuity. These results provide a more nuanced approach to considering qualitative and structural aspects of relationships that may influence sleep. PMID- 17724258 TI - Cardiac arrest in schools. AB - BACKGROUND: The purpose of the present study is to improve understanding of the epidemiology of cardiac arrest in the school setting, with a special focus on the role of school-based automated external defibrillators. METHODS AND RESULTS: The investigation was a retrospective study of emergency medical service-treated, nontraumatic, out-of-hospital cardiac arrests in Seattle and King County, Washington, that occurred in schools between 1990 and 2005. Cases were identified with cardiac arrest location data from emergency medical service cardiac arrest registries. Patient characteristics, cardiac arrest characteristics, and outcome information were abstracted from the registries and incident report forms. During the study period, 97 cardiac arrests occurred in schools, accounting for 0.4% of all treated cardiac arrests and 2.6% of public location cardiac arrests. Of the 97 cases, 12 cardiac arrests were among students, 33 among faculty and staff, and 45 among adults not employed by the school (7 adults with indeterminate school association). School-based cardiac arrest occurred on average in 1 of 111 schools annually, with a greater annual incidence among colleges (1 cardiac arrest per 8 colleges) than high schools (1 per 125 high schools) or lower-level schools (1 cardiac arrest per 200 preschools through middle schools). The estimated annual incidence of cardiac arrest was 0.18 per 100,000 person-years among students and 4.51 per 100,000 person-years for school faculty and staff. CONCLUSIONS: The present study characterizes school-setting cardiac arrest and provides a framework within which to consider preparation efforts and outcome expectations. PMID- 17724259 TI - Influence of nonfatal hospitalization for heart failure on subsequent mortality in patients with chronic heart failure. AB - BACKGROUND: Patients with chronic heart failure (HF) are at increased risk of both fatal and nonfatal major adverse cardiovascular events. We used data from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) trials to assess the influence of nonfatal hospitalizations for HF on subsequent mortality rates in a broad spectrum of HF patients. METHODS AND RESULTS: In the present study, 7599 patients with New York Heart Association class II to IV HF and reduced or preserved left ventricular ejection fraction were randomized to placebo or candesartan. We assessed the risk of death after discharge from a first hospitalization for HF using time-updated Cox proportional hazards models on 7572 patients for whom discharge data were available. Of 7572 patients, 1455 (19%) had at least 1 HF hospitalization, and 586 of 1819 deaths occurred after discharge from an HF hospitalization. The mortality rate was increased after HF hospitalizations, even after adjustment for baseline predictors of death (hazard ratio, 3.15; 95% confidence interval, 2.83 to 3.50). Longer duration of HF hospitalization enhanced the risk of dying, as did repeat HF hospitalizations. Moreover, risk of death was highest within a month of discharge and then declined progressively over time, particularly for death resulting from HF progression and for sudden cardiac death. We observed a similar pattern of risk associated with all-cause hospitalization, although the magnitude was less than that with HF hospitalization. CONCLUSIONS: In patients with chronic HF, the risk of death is greatest in the early period after discharge after a hospitalization for HF and is directly related to the duration and frequency of HF hospitalizations. These findings suggest a role for increased surveillance in the early postdischarge period of greatest vulnerability after an HF admission. PMID- 17724260 TI - Brachial artery flow-mediated dilation and asymmetrical dimethylarginine in the cardiovascular risk in young Finns study. AB - BACKGROUND: Elevated asymmetrical dimethylarginine (ADMA) is a novel risk factor for atherosclerosis that may impair endothelial function by interfering with endothelial nitric oxide synthesis. To gain insight into the effects of ADMA on systemic endothelial function, we examined the association between ADMA and brachial artery flow-mediated dilation (FMD) in a large population of young adults. METHODS AND RESULTS: Plasma ADMA and brachial FMD, as well as conventional cardiovascular risk factors, were measured in 2096 white adults aged 24 to 39 years. In univariate analysis, ADMA was inversely correlated with FMD (r=-0.07, P=0.003). The inverse association between ADMA and FMD remained significant in a multivariable regression model adjusted for age, sex, conventional cardiovascular risk factors, estimated glomerular filtration rate, and brachial artery baseline diameter (beta+/-SE -1.56+/-0.62%, P=0.01). CONCLUSIONS: We conclude that elevated plasma ADMA concentrations are associated with decreased brachial FMD responses in healthy adults. These data provide evidence at the population level that ADMA levels are associated with endothelial function. PMID- 17724261 TI - Macrophage expression of peroxisome proliferator-activated receptor-alpha reduces atherosclerosis in low-density lipoprotein receptor-deficient mice. AB - BACKGROUND: The peroxisome proliferator-activated receptor-alpha (PPARalpha) plays important roles in lipid metabolism, inflammation, and atherosclerosis. PPARalpha ligands have been shown to reduce cardiovascular events in high-risk subjects. PPARalpha expression by arterial cells, including macrophages, may exert local antiatherogenic effects independent of plasma lipid changes. METHODS AND RESULTS: To examine the contribution of PPARalpha expression by bone marrow derived cells in atherosclerosis, male and female low-density lipoprotein receptor-deficient (LDLR(-/-)) mice were reconstituted with bone marrow from PPARalpha(-/-) or PPARalpha(+/+) mice and challenged with a high-fat diet. Although serum lipids and lipoprotein profiles did not differ between the groups, the size of atherosclerotic lesions in the distal aorta of male and female PPARalpha(-/-) --> LDLR(-/-) mice was significantly increased (44% and 46%, respectively) compared with controls. Male PPARalpha(-/-) --> LDLR(-/-) mice also had larger (44%) atherosclerotic lesions in the proximal aorta than male PPARalpha(+/+) --> LDLR(-/-) mice. Peritoneal macrophages from PPARalpha(-/-) mice had increased uptake of oxidized LDL and decreased cholesterol efflux. PPARalpha(-/-) macrophages had lower levels of scavenger receptor B type I and ABCA1 protein expression and an accelerated response of nuclear factor-kappaB regulated inflammatory genes. A laser capture microdissection analysis verified suppressed scavenger receptor B type I and increased nuclear factor-kappaB gene expression levels in vivo in atherosclerotic lesions of PPARalpha(-/-) --> LDLR( /-) mice compared with the lesions of control PPARalpha(+/+) --> LDLR(-/-) mice. CONCLUSIONS: These data demonstrate that PPARalpha expression by macrophages has antiatherogenic effects via modulation of cell cholesterol trafficking and inflammatory activity. PMID- 17724262 TI - Beta2-microglobulin as a biomarker in peripheral arterial disease: proteomic profiling and clinical studies. AB - BACKGROUND: Peripheral arterial disease (PAD) is common but commonly unrecognized. Improved recognition of PAD is needed. We used high-throughput proteomic profiling to find PAD-associated biomarkers. METHODS AND RESULTS: Plasma was collected from PAD patients (ankle brachial index of <0.90; n=45) and subjects with risk factors but without PAD (n=43). Plasma was analyzed with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to quantify 1619 protein peaks. The peak intensity of a 12-kDa protein was higher in PAD patients. Western blot analyses and immunoaffinity studies confirmed that this protein was beta2-microglobulin (B2M). In a validation study, B2M was measured by ELISA in plasma in age- and gender-matched PAD (n=20) and non-PAD (n=20) subjects. Finally, we studied a larger cohort of subjects (n=237) referred for coronary angiography but without known PAD. Plasma B2M levels were higher in PAD patients than in non-PAD patients with coronary artery disease. Plasma B2M correlated with ankle brachial index and functional capacity. Independent predictors of PAD were diabetes mellitus, age, and the combination of B2M and C reactive protein level. CONCLUSIONS: In PAD patients, circulating B2M is elevated and correlates with the severity of disease independent of other risk factors. These findings might provide a needed biomarker for PAD and new insight into its pathophysiology. Further studies in other populations are needed to confirm the utility of measuring B2M in cardiovascular disease risk assessment. PMID- 17724263 TI - Risk factors related to infections of implanted pacemakers and cardioverter defibrillators: results of a large prospective study. AB - BACKGROUND: The Prospective Evaluation of Pacemaker Lead Endocarditis study is a multicenter, prospective survey of the incidence and risk factors of infectious complications after implantation of pacemakers and cardioverter-defibrillators. METHODS AND RESULTS: Between January 1, 2000, and December 31, 2000, 6319 consecutive recipients of implantable systems were enrolled at 44 medical centers and followed up for 12 months. All infectious complications were recorded, and their occurrence was related to the baseline demographic, clinical, and procedural characteristics. Among 5866 pacing systems, 3789 included 2 and 117 had >2 leads; among 453 implantable cardioverter-defibrillators, 178 were dual lead systems. A total of 4461 de novo implantations occurred and 1858 pulse generator or lead replacements. Reinterventions were performed before hospital discharge in 101 patients. Single- and multiple-variable logistic regression analyses were performed to identify risk factors; adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated. At 12 months, device-related infections were reported in 42 patients (0.68%; 95% CI, 0.47 to 0.89). The occurrence of infection was positively correlated with fever within 24 hours before the implantation procedure (aOR, 5.83; 95% CI, 2.00 to 16.98), use of temporary pacing before the implantation procedure (aOR, 2.46; 95% CI, 1.09 to 5.13), and early reinterventions (aOR, 15.04; 95% CI, 6.7 to 33.73). Implantation of a new system (aOR, 0.46; 95% CI, 0.24 to 0.87) and antibiotic prophylaxis (aOR, 0.4; 95% CI, 0.18 to 0.86) were negatively correlated with risk of infection. CONCLUSIONS: This study identified several factors of risk of device infection and confirmed the efficacy of antibiotic prophylaxis in recipients of new or replacement pacemakers or implantable cardioverter-defibrillators. PMID- 17724265 TI - In search of Andreas Roland Gruntzig, MD (1939-1985). PMID- 17724264 TI - Transient limb ischemia induces remote preconditioning and remote postconditioning in humans by a K(ATP)-channel dependent mechanism. AB - BACKGROUND: Transient limb ischemia administered before a prolonged ischemic insult has systemic protective effects against ischemia-reperfusion (IR) injury (remote ischemic preconditioning [RIPC]). It has been demonstrated that protection from IR can be achieved by brief periods of ischemia applied at a remote site during an injurious ischemic event (remote postconditioning [RPostC]). Using an in vivo model of endothelial IR injury, we sought to determine whether RPostC occurred in humans and whether it shared mechanistic similarities with RIPC. METHODS AND RESULTS: Endothelial function was assessed by flow-mediated dilation before and after IR (20 minutes of arm ischemia followed by reperfusion). RIPC was induced by conditioning cycles of 5 minutes of ischemia and reperfusion on the contralateral arm or leg before IR. For RPostC induction, conditioning cycles were administered during the ischemic phase of IR. Oral glibenclamide was used to determine the dependence of RIPC and RPostC on K(ATP) channels. IR caused a significant reduction in flow-mediated dilation in healthy volunteers (baseline, 9.3+/-1.2% versus post-IR, 3.3+/-0.7%; P<0.0001) and patients with atherosclerosis (baseline, 5.5+/-0.6% versus post-IR, 2.3+/-0.5%; P<0.01). This reduction was prevented by RIPC (post-IR+RIPC: healthy volunteers, 7.2+/-0.5% [P<0.0001 versus post-IR]; patients, 4.5+/-0.3% [P<0.01 versus post IR]) and RPostC (post-IR+RPostC: 8.0+/-0.5%; P<0.0001 versus post-IR). The protective effects of RIPC and RPostC were blocked by glibenclamide. CONCLUSIONS: This study demonstrates for the first time in humans that RPostC can be induced by transient limb ischemia and is as effective as RIPC in preventing endothelial IR injury. RIPC and RPostC share mechanistic similarities, with protection being dependent on K(ATP) channel activation. These results suggest that remote conditioning stimuli could be protective in patients with acute ischemia about to undergo therapeutic reperfusion. PMID- 17724266 TI - Images in cardiovascular medicine. Cardiac computed tomography of severe aortic endocarditis. PMID- 17724267 TI - Images in cardiovascular medicine. Ablation of atrial flutter in a patient with mustard procedure using integration of real-time electroanatomical mapping with 3 dimensional computed tomographic imaging. PMID- 17724268 TI - Letter by Rundek et al regarding article, "Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta analysis". PMID- 17724269 TI - Tyrosine hydroxylase: another piece of the genetics of hypertension puzzle. PMID- 17724270 TI - Diet and primordial prevention of cardiovascular disease in children and adolescents. PMID- 17724271 TI - Molecular imaging of cardiovascular disease. PMID- 17724272 TI - Electrophysiological interventions for inherited arrhythmia syndromes. PMID- 17724273 TI - Can large-scale trials or meta-analyses demonstrate blood pressure--independent effect of angiotensin receptor blockers? PMID- 17724274 TI - Mechanisms of fetal programming of adult hypertension: role of sex hormones. PMID- 17724275 TI - Carbon monoxide stimulates the Ca2(+)-activated big conductance k channels in cultured human endothelial cells. AB - We used the whole-cell patch-clamp technique to study K channels in the human umbilical vein endothelial cells and identified a 201 pS K channel, which was blocked by tetraethylammonium and iberiotoxin but not by TRAM34 and apamin. This suggests that the Ca(2+)-activated big-conductance K channel (BK) is expressed in endothelial cells. Application of carbon monoxide (CO) or tricarbonylchloro(glycinato)ruthenium(II), a water soluble CO donor, stimulated the BK channels. Moreover, application of hemin, a substrate of heme oxygenase, mimicked the effect of CO and increased the BK channel activity. The stimulatory effect of hemin was significantly diminished by tin mesoporphyrin, an inhibitor of heme oxygenase. To determine whether the stimulatory effect of CO on the BK channel was mediated by NO and the cGMP-dependent pathway, we examined the effect of CO on BK channels in cells treated with, N(G)-nitro-l-arginine methyl ester, 1H(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one, an inhibitor of soluble guanylate cyclase, or KT5823, an inhibitor of protein kinase G. Addition of either diethylamine NONOate or sodium nitroprusside significantly increased BK channel activity. Inhibition of endogenous NO synthesis with N(G)-nitro-l-arginine methyl ester, blocking soluble guanylate cyclase or protein kinase G, delayed but did not prevent the CO-induced activation of BK channels. Finally, application of an antioxidant agent, ebselen, had no effect on CO-mediated stimulation of BK channels in human umbilical vein endothelial cells. We conclude that BK channels are expressed in human umbilical vein endothelial cells and that they are activated by both CO and NO. CO activates BK channels directly, as well as via a mechanism involving NO or the cGMP-dependent pathway. PMID- 17724276 TI - Recombinant vascular endothelial growth factor 121 attenuates hypertension and improves kidney damage in a rat model of preeclampsia. AB - Inhibitors of angiogenic factors are known to be upregulated, and their levels increase in the maternal circulation before the onset of preeclampsia. We reproduced a previously characterized model of preeclampsia by adenoviral overexpression of the soluble vascular endothelial growth factor (VEGF) receptor sFlt-1 (also referred to as sVEGFR-1) in pregnant and nonpregnant Sprague-Dawley rats. Animals were treated with VEGF121 at 0, 100, 200, or 400 microg/kg once or twice daily (n=8 per group; 64 total) and compared with normal control animals (n=4 per group) by examination of systolic blood pressure, urinary albumin and creatinine, renal histopathology, and glomerular gene expression profiling. sFlt 1 expression induced hypertension with proteinuria and glomerular endotheliosis and significant changes in gene expression. VEGF121 treatment alleviated these symptoms and reversed 125 of 268 sFlt-1-induced changes in gene expression. VEGF121 had beneficial effects in this rat model of preeclampsia without apparent harm to the fetus. Further study of VEGF121 as a potential therapeutic agent for preeclampsia is warranted. PMID- 17724277 TI - Estrogen protects against increased blood pressure in postpubertal female growth restricted offspring. AB - Placental insufficiency in the rat results in intrauterine growth restriction and development of hypertension in prepubertal male and female growth-restricted offspring. However, after puberty, only male growth-restricted offspring remain hypertensive, whereas female growth-restricted offspring stabilize their blood pressure to levels comparable to adult female controls. Because female rats reach their maximum levels of estrogen at puberty, we hypothesize that estrogen may be a factor involved in the stabilization of blood pressure in adult female growth restricted offspring. At 10 weeks of age, female control and growth-restricted offspring underwent ovariectomy or sham surgery and insertion of a telemetry probe. Mean arterial pressure was similar at 16 weeks of age between control (123+/-4 mm Hg) and growth-restricted offspring (122+/-2 mm Hg); however, ovariectomy led to a significant increase in blood pressure in growth-restricted offspring (140+/-2 mm Hg; P<0.05 versus intact counterpart) with no significant effect in controls (124+/-1 mm Hg). Estrogen replacement by subcutaneous minipellet initiated at 14 weeks of age in a subset of ovariectomized control and growth-restricted offspring reversed the effect of ovariectomy on blood pressure in growth-restricted offspring at 16 weeks of age (111+/-3 mm Hg; P<0.05 versus ovariectomized counterpart); renin angiotensin system blockade also abolished ovariectomy-induced hypertension in female growth-restricted offspring (106+/-2 mm Hg; P<0.05 versus ovariectomized counterpart). Therefore, sex differences are observed in this model of fetal programmed hypertension, and results from this study suggest that estrogen contributes to normalization of blood pressure in adult female growth-restricted offspring. PMID- 17724278 TI - Stability of target hemoglobin levels during the first year of epoetin treatment in patients with chronic kidney disease. AB - BACKGROUND AND OBJECTIVES: Instability of hemoglobin levels during epoetin therapy is a new problem in hemodialysis. We evaluated extent and correlates of time in target, that is, the time spent with hemoglobin > or = 11 g/dl during the first year of epoetin and its association with renal survival. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data were collected in 917 visits for 12.0 mo in 119 patients with chronic kidney disease; thereafter, patients started renal survival analysis for 10.1 mo. At baseline, hemoglobin was 10.0 +/- 0.8 g/dl and GFR was 22.1 +/- 14.2 ml/min per 1.73 m2. RESULTS: Hemoglobin target, reached in 1.5 mo, was steadily maintained in only 24% of patients. Time in target was not merely due to differences in time to target; after first achievement of target, in fact, a reduction of hemoglobin < 11 g/dl occurred in 51% of patients. At multivariate analysis, male gender, basal GFR and hemoglobin levels, first epoetin dose, and iron supplementation were directly associated with length of time in target. A lower risk for renal death (dialysis n = 53; death n = 8) was detected in the higher tertile of time in target (11.3 mo) versus lower tertile (3.2 mo). This difference persisted at Cox analysis after adjustment for age, gender, GFR, BP, and proteinuria. CONCLUSIONS: In chronic kidney disease, time in target during the first year of epoetin therapy is frequently short depending not only on time to target but also on post-target hemoglobin reductions, correlates with male gender, timing, and intensity of initial therapy and is coupled with better renal survival. PMID- 17724279 TI - Teaching NeuroImage: cryptococcal brain pseudocysts in an immunocompetent patient. PMID- 17724280 TI - Does statin use decrease the amount of Alzheimer disease pathology in the brain? PMID- 17724281 TI - From paroxysmal to chronic pain in trigeminal neuralgia: implications of central sensitization. PMID- 17724282 TI - Telemedicine for acute stroke: when virtual is as good as reality. PMID- 17724283 TI - Zolmitriptan nasal spray in the acute treatment of cluster headache: a double blind study. AB - OBJECTIVE: To evaluate the efficacy and tolerability of zolmitriptan 5 mg and 10 mg nasal spray (ZNS) vs placebo in the acute treatment of cluster headache. Design/ METHODS: We conducted a multicenter, double-blind, randomized, three period crossover study using ZNS 5 mg, ZNS 10 mg, and placebo. Headache intensity was rated by a 5-point scale: none, mild, moderate, severe, or very severe. The primary efficacy measure was headache response (pain reduced from moderate, severe, or very severe at baseline, to mild or none) at 30 minutes. Logistic regression was used to account for treatment period effect as well as for cluster headache subtype effect. RESULTS: A total of 52 adult patients treated 151 attacks. For the primary endpoint, both doses reached significance at 30 minutes (placebo = 30%, ZNS 5 mg = 50%, ZNS 10 mg = 63.3%). For headache relief, ZNS 10 mg separated from placebo at 10 minutes (24.5% vs 10%). Zolmitriptan 5 mg separated from placebo at 20 minutes (38.5% vs 20%). For pain-free status, ZNS 10 mg was superior to placebo at 15 minutes (22.0% vs 6%). Both doses had higher pain-free rates than placebo at 30 minutes (placebo = 20%, ZNS 5 mg = 38.5%, ZNS 10 mg = 46.9%). Side effects were mild and seen in 16% of those attacks treated with placebo, 25% of attacks treated with ZNS 5 mg, and 32.7% treated with ZNS 10 mg. CONCLUSIONS/RELEVANCE: Zolmitriptan nasal spray, at doses of 5 and 10 mg, is effective and tolerable for the acute treatment of cluster headache. PMID- 17724284 TI - Motor cortex stimulation for pain control induces changes in the endogenous opioid system. AB - BACKGROUND: Motor cortex stimulation (MCS) for neuropathic pain control induces focal cerebral blood flow changes involving regions with high density of opioid receptors. We studied the possible contribution of the endogenous opioid system to MCS-related pain relief. METHODS: Changes in opioid receptor availability induced by MCS were studied with PET scan and [(11)C]diprenorphine in eight patients with refractory neuropathic pain. Each patient underwent two preoperative (test-retest) PET scans and one postoperative PET scan acquired after 7 months of chronic MCS. RESULTS: The two preoperative scans, performed at 2 weeks interval, did not show significant differences. Conversely, postoperative compared with preoperative PET scans revealed significant decreases of [(11)C]diprenorphine binding in the anterior middle cingulate cortex (aMCC), periaqueductal gray (PAG), prefrontal cortex, and cerebellum. Binding changes in aMCC and PAG were significantly correlated with pain relief. CONCLUSION: The decrease in binding of the exogenous ligand was most likely explained by receptor occupancy due to enhanced secretion of endogenous opioids. Motor cortex stimulation (MCS) may thus induce release of endogenous opioids in brain structures involved in the processing of acute and chronic pain. Correlation of this effect with pain relief in at least two of these structures supports the role of the endogenous opioid system in pain control induced by MCS. PMID- 17724285 TI - Impaired trigeminal nociceptive processing in patients with trigeminal neuralgia. AB - BACKGROUND: Trigeminal neuralgia (TN) usually leads to paroxysms of short lasting but very severe pain. Between the attacks the patient is usually asymptomatic, but a constant dull background pain may persist in some cases. The mechanisms associated with the development of this chronic pain are not well understood. OBJECTIVE: To determine trigeminal nociceptive fiber impairment in patients with TN comparing symptomatic and nonsymptomatic sides using the nociceptive blink reflex (nBR) and pain-related evoked potentials (PREP) and to identify possible central mechanisms of pain chronicity. METHODS: We investigated 24 patients with TN without and 18 patients with TN with concomitant chronic facial pain. PREP and nBR were investigated following nociception specific electrical stimulation on both sides of the face and in each division of the trigeminal nerve (V1, V2, and V3). RESULTS: We found prolonged PREP and nBR latencies and reduced amplitudes comparing symptomatic and nonsymptomatic sides in all patients with TN. In patients with chronic facial pain, however, PREP amplitudes were larger and latencies shorter compared to patients with TN without facial pain, while nBR results were similar across groups. CONCLUSION: The data suggest an impairment of the trigeminal nociceptive system due to demyelination and/or axonal dysfunction on the symptomatic side and locate this defect close to the root entry zone in the brainstem. Moreover, central facilitation of trigeminal nociceptive processing was observed in patients with trigeminal neuralgia with concomitant chronic facial pain indicating overactivation of central sensory transmission. This may represent a possible adaptive mechanism for the development of chronic pain. PMID- 17724286 TI - Morphometric fingerprint of asymptomatic Parkin and PINK1 mutation carriers in the basal ganglia. AB - BACKGROUND: Mutations in the Parkin and PINK1 genes can cause parkinsonism. Since asymptomatic carriers of a single mutant allele of the Parkin or PINK1 gene display a presynaptic dopaminergic dysfunction in the striatum, they provide a unique in vivo model to study structural and functional reorganization in response to latent nigrostriatal dysfunction. We hypothesized that subclinical nigrostriatal neurodegeneration caused by these mutations would induce morphologic changes in the dysfunctional striatal gray matter. METHODS: In asymptomatic carriers of a heterozygous Parkin (n = 13) or PINK1 (n = 10) mutation and 23 age-and sex-matched individuals without a mutation, we applied observer independent region-of-interest and voxel-based morphometry to high resolution structural MRIs. RESULTS: Relative to controls without a mutation, Parkin and PINK1 mutation carriers displayed a bilateral increase in gray matter volume in the putamen and the internal globus pallidus. In 8 of the 13 Parkin mutation carriers, the presynaptic dopaminergic function was studied with (18)F DOPA PET. The metabolic-morphometric regression analysis revealed that the linear decrease in individual presynaptic striatal (18)F-DOPA uptake was linked to a reciprocal decrease in the striatal gray matter volume in the putamen bilaterally and in the left caudate nucleus. CONCLUSIONS: The alternative causes of the increased striatal gray matter volume may be either due to excessive levels of neuronal activity caused by chronic dopaminergic dysfunction or due to long-term adaptation to chronic nigrostriatal dysfunction actively compensating for the dopaminergic denervation. In any case, the results indicate that a genetically driven regional dysfunction may be imprinted in the structure of the dysfunctional brain region, for example in the striatum. PMID- 17724287 TI - Volumetric brain changes in females with fragile X-associated tremor/ataxia syndrome (FXTAS). AB - BACKGROUND: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder occurring in male and rare female carriers of a premutation expansion (55 to 200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene. METHODS: Volumetric MRI studies, clinical staging, cognitive testing, and molecular analysis were conducted in 15 female premutation carriers affected by FXTAS (age 59.5 +/- 10.3 years), 20 unaffected female carriers (43.3 +/- 11.2 years), 11 genetically normal female controls (51.0 +/- 10.3 years), 36 affected male carriers (65.0 +/- 5.6 years), 25 unaffected male carriers (53.5 +/ 12.5 years), and 39 male controls (58.0 +/- 15.0 years). Female and male carriers with FXTAS were matched on duration of disease. RESULTS: We found less pronounced reductions of cerebellar volume and a lower incidence of involvement (symmetric high T2 signal) of the middle cerebellar peduncles (MCP sign) in females affected by FXTAS (13%) compared with affected males (58%). We found reduced brain volumes and increased white matter disease associated with the presence of FXTAS in females compared with female controls. We also observed significant associations between reduced cerebellar volume and both increased severity of FXTAS symptoms and increased length of the CGG repeat expansion in male premutation carriers, but not in females. CONCLUSIONS: Females affected by fragile X-associated tremor/ataxia syndrome (FXTAS) demonstrated milder brain changes than affected males, although they showed a similar pattern of radiologic findings consistent with brain atrophy and white matter disease. FXTAS should be considered (by ordering fragile X DNA testing) in females who present with late onset ataxia, action tremor, or neuropathy, particularly in those with a family history of mental retardation, autism, or premature ovarian failure. PMID- 17724288 TI - Investigations of face expertise in the social developmental disorders. AB - BACKGROUND: Patients with social developmental disorders (SDD), also known as autism spectrum disorders, may have impaired recognition of facial identity or facial expressions. OBJECTIVE: Our goal was to determine whether SDDs were characterized by loss of a perceptual mechanism responsible for face expertise, as current theories suggest that such a loss should be selective for upright faces, disproportionately affect the perception of facial configuration, and possibly be more severe in the eye region. METHOD: We tested a group of 24 adult patients with SDD with an oddity paradigm that required them to detect changes in facial configuration or feature color, in either the eyes or the mouth, in both upright and inverted faces. RESULTS: One group of subjects with SDD with normal famous face recognition had only a mild reduction in accuracy and a normal pattern of inversion effects. A second group of subjects with SDD with impaired famous face recognition had a severe reduction of accuracy. This deficit was not limited to upright faces. It affected the perception of feature configuration and feature color to a similar degree and both eye and mouth changes were discriminated poorly in upright faces. CONCLUSION: The impaired face recognition that is present in a subset of patients with social developmental disorders is accompanied by impaired face perception, and this impairment is not exclusive to upright faces, facial configuration, or the eye region. The reduced face processing skills in these subjects may be more consistent with recent computational models of face expertise than with classic dual-route hypotheses. PMID- 17724289 TI - What does fluorodeoxyglucose PET imaging add to a clinical diagnosis of dementia? AB - BACKGROUND: Few studies have compared the accuracy of [(18)F]fluorodeoxyglucose (FDG) PET to the accuracy of clinical and pathologic diagnosis in dementia patients. METHODS: Forty-four individuals with dementia, cognitive impairment, or normal cognitive function underwent clinical initial evaluation (IE) and PET scanning and were followed up for approximately 4 years until a final evaluation (FE) and 5 years until death and autopsy. Clinical, pathologic, and imaging diagnoses were categorized as Alzheimer disease (AD) or not AD. RESULTS: Sensitivity of the IE for the pathologic diagnosis of AD was 0.76, and specificity was 0.58; PET had values of 0.84 and 0.74, and FE had values of 0.88 and 0.63. Positive predictive values for IE, PET, and FE were 0.70, 0.81, and 0.76. Negative predictive values were 0.65, 0.78, and 0.80. The diagnosis of AD was associated with a 70% probability of detecting AD pathology; with a positive PET scan this increased to 84%, and with a negative PET scan this decreased to 31%. A diagnosis of not AD at IE was associated with a 35% probability of AD pathology, increasing to 70% with a positive PET scan. CONCLUSIONS: As a diagnostic tool, PET is superior to a baseline clinical evaluation and similar to an evaluation performed 4 years later. Although the addition of [(18)F]fluorodeoxyglucose PET to a clinical diagnosis provides useful information that can affect the likelihood of detecting Alzheimer disease pathology, the value of this technique in the current clinical environment with limited therapeutic options is likely to be modest. PMID- 17724290 TI - Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease. AB - BACKGROUND: Treatment with 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors ("statins") has been associated in some epidemiologic studies with reduced risk of Alzheimer disease (AD). However, direct evidence of statin effects on neuropathologic markers of AD is lacking. We investigated whether antecedent statin exposure is associated with neuritic plaque (NP) or neurofibrillary tangle (NFT) burden in a population-based sample of human subjects. METHODS: Brain autopsies were performed on 110 subjects, ages 65 to 79 years, who were cognitively normal at enrollment into the Adult Changes in Thought Study. Neuropathologic findings were compared between statin users with > or =3 prescriptions of > or =15 pills of simvastatin, pravastatin, lovastatin, or atorvastatin vs nonusers, based on pharmacy dispensing records. RESULTS: After controlling for age at death, gender, cognitive function at study entry, brain weight, and presence of cerebral microvascular lesions, the odds ratio (OR) for each unit increase in Braak NFT stage in statin users vs nonusers was 0.44 (95% CI: 0.20 to 0.95). The OR for each unit increase in Consortium to Establish a Registry for Alzheimer's Disease (CERAD) staging of NPs did not deviate significantly from unity (OR 0.69; 95% CI: 0.32 to 1.52). However, the risk for typical AD pathology (Braak stage > or = IV and CERAD rating > or = moderate) was reduced in statin users (OR 0.20; 95% CI: 0.05 to 0.86). CONCLUSIONS: These findings demonstrate an association between antecedent statin use and neurofibrillary tangle burden at autopsy. Additional study is needed to examine whether statin use may be causally related to decreased development of Alzheimer disease-related neuropathologic changes. PMID- 17724291 TI - In-hospital mortality of generalized convulsive status epilepticus: a large US sample. AB - OBJECTIVE: To evaluate the in-hospital mortality associated with generalized convulsive status epilepticus (GCSE), and predictors of death in a large US cohort. METHODS: We identified our cohort from the National Inpatient Sample for the years 2000 through 2004 by searching the International Classification of Diseases, Ninth Revision, code for GCSE. We excluded patients with partial status epilepticus, and assessed whether associated diagnoses including brain tumors, CNS infections, stroke, hypoxic-ischemic brain injury, metabolic derangements, and respiratory failure predicted mortality. We used logistic regression models to identify predictors of death. RESULTS: Eleven thousand five hundred eighty patients were included in this analysis. The mean age of the patients was 39 +/- 25.6 years, and the median duration of stay was 3 days. Male sex (53.4%) and white race (42.4%) were predominant. Overall in-hospital mortality was 399 in 11,580 (3.45%). Age was a significant predictor of death. Mortality tripled in those who received mechanical ventilation compared with those who did not (7.43% vs 2.22%, odds ratio [OR] 2.79, 95% CI 2.18 to 3.59). Other predictors of mortality included hypoxic-ischemic brain injury (OR 9.85, 95% CI 6.63 to 14.6), cerebrovascular diseases (OR 2.08, 95% CI 1.13 to 3.82), female sex (OR 1.34, 95% CI 1.04 to 1.73), and higher comorbidity index (OR 6.79, 95% CI 4.27 to 10.8). CONCLUSION: Overall in-hospital mortality from generalized convulsive status epilepticus is low, but remarkably increases in those treated with mechanical ventilation. Other predictors of mortality include older age, female sex, hypoxic ischemic brain injury, and higher comorbidity index. PMID- 17724292 TI - Status epilepticus as initial manifestation of posterior reversible encephalopathy syndrome. AB - We report 10 cases of status epilepticus (SE) in patients with posterior reversible encephalopathy syndrome (PRES). In all cases, SE brought PRES to medical attention. The majority of the cases had focal-onset complex partial SE. Complete resolution of SE was achieved after combined treatment of PRES and SE in all cases. SE in the setting of PRES carries a favorable prognosis but requires timely recognition and treatment of the course of PRES. PMID- 17724293 TI - Long-term outcome after thrombolysis in telemedical stroke care. AB - BACKGROUND: IV thrombolysis represents the most effective acute stroke therapy. However, it is almost exclusively performed in stroke centers and is not available in most community areas. The Telemedical Pilot Project for Integrative Stroke Care (TEMPiS) was started in February 2003. Twelve community hospitals with no or very limited stroke thrombolysis experience and two stroke centers were connected via a network providing online neurologic examination and transfer of neuroradiologic scans. Following recently published preliminary results on acute phase safety of telethrombolysis, the present study reports on its long term functional outcome. METHODS: Modified Rankin Scale (mRS), Barthel Index (BI), and mortality rate were prospectively collected 3 and 6 months after IV thrombolysis in patients of community network hospitals (telemedical group) and the stroke centers. Values of 95/100 for the BI and 0/1 for the mRS were defined as a favorable outcome. RESULTS: Over the first 22 months, 170 patients were treated with tPA in the telemedical hospitals and 132 in the stroke center hospitals. Mortality rates were 11.2% vs 11.5% at 3 months (p = 0.55) and 14.2% vs 13% at 6 months (p = 0.45). A good functional outcome after 6 months was found in 39.5% of the telemedical hospitals vs 30.9% of the stroke centers (p = 0.10) for the mRS and 47.1% vs 44.8% (p = 0.44) regarding the BI. CONCLUSIONS: Mortality rates and functional outcomes for telemedicine-linked community hospitals and stroke centers were similar and comparable to the results from randomized trials. PMID- 17724294 TI - Statin treatment withdrawal in ischemic stroke: a controlled randomized study. AB - BACKGROUND: Pretreatment with statins has been shown to reduce brain injury in cerebral ischemia. In this controlled randomized study, we investigated the influence of statin pretreatment and its withdrawal on the outcome of acute ischemic stroke patients. METHODS: From 215 patients admitted within 24 hours of a hemispheric ischemic stroke, 89 patients on chronic statin treatment were randomly assigned either to statin withdrawal for the first 3 days after admission (n = 46) or to immediately receive atorvastatin 20 mg/day (n = 43). The primary outcome event was death or dependency (modified Rankin Scale [mRS] score > 2) at 3 months. Early neurologic deterioration (END) and infarct volume at days 4 to 7 were secondary outcome variables. In a secondary analysis, outcome variables were compared with the nonrandomized patients without previous statin therapy (n = 126). RESULTS: Patients with statin withdrawal showed a higher frequency of mRS score > 2 at the end of follow-up (60.0% vs 39.0%; p = 0.043), END (65.2% vs 20.9%; p < 0.0001), and greater infarct volume (74 [45, 126] vs 26 [12, 70] mL; p = 0.002) compared with the non-statin-withdrawal group. Statin withdrawal was associated with a 4.66 (1.46 to 14.91)-fold increase in the risk of death or dependency, a 8.67 (3.05 to 24.63)-fold increase in the risk of END, and an increase in mean infarct volume of 37.63 mL (SE 10.01; p < 0.001) after adjusting for age and baseline stroke severity. Compared with patients without previous treatment with statins, statin withdrawal was associated with a 19.01 (1.96 to 184.09)-fold increase in the risk of END and an increase in mean infarct volume of 43.51 mL (SE 21.91; p = 0.048). CONCLUSION: Statin withdrawal is associated with increased risk of death or dependency at 90 days. Hence, this treatment should be continued in the acute phase of ischemic stroke. PMID- 17724295 TI - Homoplasmy, heteroplasmy, and mitochondrial dystonia. AB - BACKGROUND: In clinical practice, mitochondrial disease is seldom considered until a variable combination of seizures, alteration in tone, muscle weakness, and developmental problems is evident. However, it is not uncommon for one symptom to occur in isolation and dominate the clinical phenotype. We report six patients from two families where dystonia was the principal clinical manifestation. A mitochondrial etiology was considered in each case because of the association of dystonia with other less prominent clinical features such as epilepsy. METHODS: Histochemical and biochemical analyses were undertaken in skeletal muscle biopsies from individuals in both families. Sequencing of skeletal muscle mtDNA was also performed and suspected mutations were quantified by hot last cycle PCR-RFLP or primer extension assay. Functional consequences of one of the mutations were investigated by measurement of steady state levels of mitochondrial tRNA. RESULTS: Two distinct mitochondrial pathologies were identified: a novel, homoplasmic mitochondrial tRNA(Cys) (MTTC) mutation and the primary, m.11778G>A Leber hereditary optic neuropathy (LHON) mutation. The mild nature of both mutations has permitted very high levels of mutated mtDNA to accumulate. Patients with the mutation in the MTTC gene have no wild type mtDNA detectable and although the LHON mutation is heteroplasmic in the patients we report, it is commonly observed to be homoplasmic. CONCLUSIONS: The mitochondrial etiology identified in these patients emphasizes the pathologic potential of homoplasmic mutations and has important implications for the investigation and genetic counseling of families where dystonia is the principal clinical feature. We advocate that mitochondrial disease should be given serious consideration in patients with familial, progressive dystonia, particularly when additional neurologic features such as epilepsy are present. PMID- 17724297 TI - Superficial siderosis and csf hypovolemia: the defect (dural) in the link. PMID- 17724296 TI - Brain MRI in mucopolysaccharidosis: effect of aging and correlation with biochemical findings. AB - OBJECTIVE: To investigate the influence of aging on conventional MRI and magnetic resonance spectroscopy (MRS) findings of mucopolysaccharidosis (MPS) patients and to test the correlation of enzyme levels, urinary glycosaminoglycans (GAG), and neuroimaging findings. METHODS: Sixty patients with MPS types I (n = 8), II (n = 31), IV-A (n = 4), and VI (n = 17) underwent T2, fluid-attenuated inversion recovery (FLAIR), and MRS of the brain. For analysis of MRI variables, we measured the normalized cerebral volume (NCV), CSF volume (NCSFV), ventricular volume (NVV), and lesion load (NLL) on FLAIR using semiautomated and automated segmentation techniques. For MRS, a point-resolved spectroscopy technique was used. Voxels were positioned at the white and gray matter. Statistical analysis involved Pearson or Spearman tests for correlation between neuroimaging, age, enzyme levels, and urinary GAG. RESULTS: The median age at onset of the disease was 20 months. Patients with longer disease duration had more NLL in the white matter (r = 0.28, p = 0.03), and this difference was more pronounced in MPS II patients (r = 0.44, p = 0.02). Metabolites ratios in MRS, NCV, NCSFV, and NVV did not correlate with disease duration or age of the patients (p > 0.05). MRI and MRS variables in either the white or the gray matter did not correlate with enzymatic activity or GAG levels. Patients with MPS II had a lower mean NCV (p < 0.001). CONCLUSIONS: Our data showed that white matter lesion is more extensive as disease duration increases, especially in mucopolysaccharidosis type II patients. MRI and magnetic resonance spectroscopy findings did not correlate with either enzymatic or glycosaminoglycan levels. PMID- 17724298 TI - Apraxic agraphia following a right cerebellar hemorrhage. PMID- 17724299 TI - Lead poisoning from the beauty case: neurologic manifestations in an elderly woman. PMID- 17724300 TI - The case of the colorless crystals. PMID- 17724301 TI - Intratumoral hemorrhage after thrombolysis in a patient with glioblastoma multiforme. PMID- 17724302 TI - Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy. PMID- 17724303 TI - Longitudinal follow-up of "benign" multiple sclerosis at 20 years. PMID- 17724304 TI - Effect of referral bias on assessing survival in als. PMID- 17724305 TI - Jack Ruby. PMID- 17724306 TI - Counterpoint: Satellite cell addition is not obligatory for skeletal muscle hypertrophy. PMID- 17724309 TI - In response to Point:Counterpoint: "Satellite cell addition is/is not obligatory for skeletal muscle hypertrophy". PMID- 17724310 TI - Last Word on Point:Counterpoint: Satellite cell addition is/is not obligatory for skeletal muscle hypertrophy. PMID- 17724311 TI - Proper "normalization" of flow-mediated dilation for shear. PMID- 17724313 TI - Human papillomavirus vaccine: waiting for a miracle. PMID- 17724314 TI - Colleges contemplate revising post-graduate medical education. PMID- 17724315 TI - Three provinces to study 2-dose HPV vaccine. PMID- 17724316 TI - Pass me that scalpel, instrumentalist. PMID- 17724317 TI - Nova Scotia paramedics to be wired. PMID- 17724318 TI - WHO regulations to prevent spread of infectious disease. PMID- 17724319 TI - The next wave: "physician extenders"? PMID- 17724320 TI - Libya negotiates deal for release of doctor, 5 nurses. PMID- 17724321 TI - Red in the desert. PMID- 17724322 TI - A Canadian immigrant with coinfection of Strongyloides stercoralis and human T lymphotropic virus 1. PMID- 17724323 TI - A 71-year-old woman with abdominal pain and acute renal failure. PMID- 17724324 TI - Human papillomavirus vaccines launch a new era in cervical cancer prevention. PMID- 17724325 TI - Patient information about HPV and the HPV vaccine. PMID- 17724326 TI - Feasibility of self-collection of specimens for human papillomavirus testing in hard-to-reach women. AB - To study the feasibility of self-collected specimens for testing human papillomavirus (HPV) status among hard-to-reach women, outreach nurses recruited women in women's centres, shelters and alleys in Vancouver's Downtown Eastside. Of the 151 participants for whom samples were available, 43 (28.5%) tested positive for high-risk HPV. Outreach nurses were able to recontact 81.4% of the participants who tested positive and referred them for further testing. About 14% (21/151) of participants had never received a Papanicolaou smear in British Columbia, as compared with 8.3% (608/7336) of women in the BC general population (p < 0.05). This difference suggests that self-collection of specimens for HPV testing is a feasible method to reach women who have not previously participated in cervical cancer screening programs. PMID- 17724328 TI - Lactate and the osmolar gap. PMID- 17724329 TI - "Emotional incontinence". PMID- 17724330 TI - Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. AB - Glucagon-like peptide-1 (GLP-1), released from gut endocrine L cells in response to glucose, regulates appetite, insulin secretion, and gut motility. How glucose given orally, but not systemically, induces GLP-1 secretion is unknown. We show that human duodenal L cells express sweet taste receptors, the taste G protein gustducin, and several other taste transduction elements. Mouse intestinal L cells also express alpha-gustducin. Ingestion of glucose by alpha-gustducin null mice revealed deficiencies in secretion of GLP-1 and the regulation of plasma insulin and glucose. Isolated small bowel and intestinal villi from alpha gustducin null mice showed markedly defective GLP-1 secretion in response to glucose. The human L cell line NCI-H716 expresses alpha-gustducin, taste receptors, and several other taste signaling elements. GLP-1 release from NCI H716 cells was promoted by sugars and the noncaloric sweetener sucralose, and blocked by the sweet receptor antagonist lactisole or siRNA for alpha-gustducin. We conclude that L cells of the gut "taste" glucose through the same mechanisms used by taste cells of the tongue. Modulating GLP-1 secretion in gut "taste cells" may provide an important treatment for obesity, diabetes and abnormal gut motility. PMID- 17724331 TI - An extracellular region of the erythropoietin receptor of the subterranean blind mole rat Spalax enhances receptor maturation. AB - Erythropoietic functions of erythropoietin (EPO) are mediated by its receptor (EPO-R), which is present on the cell surface of erythroid progenitors and induced by hypoxia. We focused on EPO-R from Spalax galili (sEPO-R), one of the four Israeli species of the subterranean blind mole rat, Spalax ehrenbergi superspecies, as a special natural animal model of high tolerance to hypoxia. Led by the intriguing observation that most of the mouse EPO-R (mEPO-R) is retained in the endoplasmic reticulum (ER), we hypothesized that sEPO-R is expressed at higher levels on the cell surface, thus maximizing the response to elevated EPO, which has been reported in this species. Indeed, we found increased cell-surface levels of sEPO-R as compared with mEPO-R by using flow cytometry analysis of BOSC cells transiently expressing HA-tagged EPO-Rs (full length or truncated). We then postulated that unique extracellular sEPO-R sequence features contribute to its processing and cell-surface expression. To map these domains of the sEPO-R that augment receptor maturation, we generated EPO-R derivatives in which parts of the extracellular region of mEPO-R were replaced with the corresponding fragments of sEPO-R. We found that an extracellular portion of sEPO-R, harboring the N glycosylation site, conferred enhanced maturation and increased transport to the cell surface of the respective chimeric receptor. Taken together, we demonstrate higher surface expression of sEPO-R, attributed at least in part to increased ER exit, mediated by an extracellular region of this receptor. We speculate that these sEPO-R sequence features play a role in the adaptation of Spalax to extreme hypoxia. PMID- 17724333 TI - Retraction: "Vitamin C conjugates of genotoxic lipid peroxidation products: structural characterization and detection in human plasma". PMID- 17724332 TI - T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1. AB - Dietary sugars are transported from the intestinal lumen into absorptive enterocytes by the sodium-dependent glucose transporter isoform 1 (SGLT1). Regulation of this protein is important for the provision of glucose to the body and avoidance of intestinal malabsorption. Although expression of SGLT1 is regulated by luminal monosaccharides, the luminal glucose sensor mediating this process was unknown. Here, we show that the sweet taste receptor subunit T1R3 and the taste G protein gustducin, expressed in enteroendocrine cells, underlie intestinal sugar sensing and regulation of SGLT1 mRNA and protein. Dietary sugar and artificial sweeteners increased SGLT1 mRNA and protein expression, and glucose absorptive capacity in wild-type mice, but not in knockout mice lacking T1R3 or alpha-gustducin. Artificial sweeteners, acting on sweet taste receptors expressed on enteroendocrine GLUTag cells, stimulated secretion of gut hormones implicated in SGLT1 up-regulation. Gut-expressed taste signaling elements involved in regulating SGLT1 expression could provide novel therapeutic targets for modulating the gut's capacity to absorb sugars, with implications for the prevention and/or treatment of malabsorption syndromes and diet-related disorders including diabetes and obesity. PMID- 17724335 TI - Multidimensional ultrafast spectroscopy special feature: multidimensional ultrafast spectroscopy. PMID- 17724334 TI - Reprogramming of keratin biosynthesis by sulforaphane restores skin integrity in epidermolysis bullosa simplex. AB - Epidermolysis bullosa simplex (EBS) is a rare inherited condition in which the epidermis loses its integrity after mechanical trauma. EBS is typified by the dysfunction of intermediate filaments in basal keratinocytes of epidermis. Most cases of EBS are due to mutations in the keratin 5 or 14 gene (K5 and K14), whose products copolymerize to form intermediate filaments in basal keratinocytes. Available treatments for this disorder are only palliative. Here we exploit functional redundancy within the keratin gene family as the basis for therapy. We show that genetic activation of Gli2 or treatment with a pharmacological activator of Nrf2, two transcription factors eliciting distinct transcriptional programs, alleviates the blistering caused by a K14 deficiency in an EBS mouse model, correlating with K17 induction in basal epidermal keratinocytes. Nrf2 induction is brought about by treatment with sulforaphane, a natural product. Sulforaphane thus represents an attractive option for the prevention of skin blistering associated with K14 mutations in EBS. PMID- 17724336 TI - Central serotonergic neurons are differentially required for opioid analgesia but not for morphine tolerance or morphine reward. AB - Opioids remain the most effective analgesics despite their potential adverse effects such as tolerance and addiction. Mechanisms underlying these opiate mediated processes remain the subject of much debate. Here we describe opioid induced behaviors of Lmx1b conditional knockout mice (Lmx1bf/f/p), which lack central serotonergic neurons, and we report that opioid analgesia is differentially dependent on the central serotonergic system. Analgesia induced by a kappa opioid receptor agonist administered at the supraspinal level was abolished in Lmx1bf/f/p mice compared with their wild-type littermates. Furthermore, compared with their wild-type littermates Lmx1bf/f/p mice exhibited significantly reduced analgesic effects of mu and delta opioid receptor agonists at both spinal and supraspinal sites. In contrast to the attenuation in opioid analgesia, Lmx1bf/f/p mice developed tolerance to morphine analgesia and displayed normal morphine reward behavior as measured by conditioned place preference. Our results provide genetic evidence supporting the view that the central serotonergic system is a key component of supraspinal pain modulatory circuitry mediating opioid analgesia. Furthermore, our data suggest that the mechanisms of morphine tolerance and morphine reward are independent of the central serotonergic system. PMID- 17724337 TI - Neuronal population coding of continuous and discrete quantity in the primate posterior parietal cortex. AB - Quantitative knowledge guides vital decisions in the life of animals and humans alike. The posterior parietal cortex in primates has been implicated in representing abstract quantity, both continuous (extent) and discrete (number of items), supporting the idea of a putative generalized magnitude system in this brain area. Whether or not single neurons encode different types of quantity, or how quantitative information is represented in the neuronal responses, however, is unknown. We show that length and numerosity are encoded by functionally overlapping groups of parietal neurons. Using a statistical classifier, we found that the activity of populations of quantity-selective neurons contained accurate information about continuous and discrete quantity. Unexpectedly, even neurons that were nonselective according to classical spike-count measures conveyed robust categorical information that predicted the monkeys' quantity judgments. Thus, different information-carrying processes of partly intermingled neuronal networks in the parietal lobe seem to encode various forms of abstract quantity. PMID- 17724338 TI - Contribution of the receptor guanylyl cyclase GC-D to chemosensory function in the olfactory epithelium. AB - The mammalian main olfactory epithelium (MOE) recognizes and transduces olfactory cues through a G protein-coupled, cAMP-dependent signaling cascade. Additional chemosensory transduction mechanisms have been suggested but remain controversial. We show that a subset of MOE neurons expressing the orphan receptor guanylyl cyclase GC-D and the cyclic nucleotide-gated channel subunit CNGA3 employ an excitatory cGMP-dependent transduction mechanism for chemodetection. By combining gene targeting of Gucy2d, which encodes GC-D, with patch clamp recording and confocal Ca2+ imaging from single dendritic knobs in situ, we find that GC-D cells recognize the peptide hormones uroguanylin and guanylin as well as natural urine stimuli. These molecules stimulate an excitatory, cGMP-dependent signaling cascade that increases intracellular Ca2+ and action potential firing. Responses are eliminated in both Gucy2d- and Cnga3 null mice, demonstrating the essential role of GC-D and CNGA3 in the transduction of these molecules. The sensitive and selective detection of two important natriuretic peptides by the GC-D neurons suggests the possibility that these cells contribute to the maintenance of salt and water homeostasis or the detection of cues related to hunger, satiety, or thirst. PMID- 17724339 TI - Risky prey behavior evolves in risky habitats. AB - Longstanding theory in behavioral ecology predicts that prey should evolve decreased foraging rates under high predation threat. However, an alternative perspective suggests that growth into a size refuge from gape-limited predation and the future benefits of large size can outweigh the initial survival costs of intense foraging. Here, I evaluate the relative contributions of selection from a gape-limited predator (Ambystoma opacum) and spatial location to explanations of variation in foraging, growth, and survival in 10 populations of salamander larvae (Ambystoma maculatum). Salamander larvae from populations naturally exposed to intense A. opacum predation risk foraged more actively under common garden conditions. Higher foraging rates were associated with low survival in populations exposed to free-ranging A. opacum larvae. Results demonstrate that risky foraging activity can evolve in high predation-risk habitats when the dominant predators are gape-limited. This finding invites the further exploration of diverse patterns of prey foraging behavior that depends on natural variation in predator size-selectivity. In particular, prey should adopt riskier behaviors under predation threat than expected under existing risk allocation models if foraging effort directly reduces the duration of risk by growth into a size refuge. Moreover, evidence from this study suggests that foraging has evolved over microgeographic scales despite substantial modification by regional gene flow. This interaction between local selection and spatial location suggests a joint role for adaptation and maladaptation in shaping species interactions across natural landscapes, which is a finding with implications for dynamics at the population, community, and metacommunity levels. PMID- 17724340 TI - Dichotomy and perceptual distortions in absolute pitch ability. AB - Absolute pitch (AP) is the rare ability to identify the pitch of a tone without the aid of a reference tone. Understanding both the nature and genesis of AP can provide insights into neuroplasticity in the auditory system. We explored factors that may influence the accuracy of pitch perception in AP subjects both during the development of the trait and in later age. We used a Web-based survey and a pitch-labeling test to collect perceptual data from 2,213 individuals, 981 (44%) of whom proved to have extraordinary pitch-naming ability. The bimodal distribution in pitch-naming ability signifies AP as a distinct perceptual trait, with possible implications for its genetic basis. The wealth of these data has allowed us to uncover unsuspected note-naming irregularities suggestive of a "perceptual magnet" centered at the note "A." In addition, we document a gradual decline in pitch-naming accuracy with age, characterized by a perceptual shift in the "sharp" direction. These findings speak both to the process of acquisition of AP and to its stability. PMID- 17724341 TI - Analysis of potential transcriptomic biomarkers for Huntington's disease in peripheral blood. AB - Highly quantitative biomarkers of neurodegenerative disease remain an important need in the urgent quest for disease-modifying therapies. For Huntington's disease (HD), a genetic test is available (trait marker), but necessary state markers are still in development. In this report, we describe a large battery of transcriptomic tests explored as state biomarker candidates. In an attempt to exploit the known neuroinflammatory and transcriptional perturbations of disease, we measured relevant mRNAs in peripheral blood cells. The performance of these potential markers was weak overall, with only one mRNA, immediate early response 3 (IER3), showing a modest but significant increase of 32% in HD samples compared with controls. No statistically significant differences were found for any other mRNAs tested, including a panel of 12 RNA biomarkers identified in a previous report [Borovecki F, Lovrecic L, Zhou J, Jeong H, Then F, Rosas HD, Hersch SM, Hogarth P, Bouzou B, Jensen RV, et al. (2005) Proc Natl Acad Sci USA 102:11023 11028]. The present results may nonetheless inform the future design and testing of HD biomarker strategies. PMID- 17724342 TI - Structure of the Cyclin T binding domain of Hexim1 and molecular basis for its recognition of P-TEFb. AB - Hexim1 is a cellular protein that associates with the positive transcription elongation factor b (P-TEFb) to regulate RNA polymerase II elongation of nascent mRNA transcripts. It directly binds to Cyclin T1 of P-TEFb and inhibits the kinase activity of Cdk9, leading to an arrest of transcription elongation. Here, we report the solution structure of the Cyclin T binding domain (TBD) of Hexim1 that forms a parallel coiled-coil homodimer composed of two segments and a preceding alpha helix that folds back onto the first coiled-coil unit. NMR titration, fluorescence, and immunoprecipitation experiments revealed the binding interface to Cyclin T1, which covers a large surface on the first coiled-coil segment. Electrostatic interactions between an acidic patch on Hexim1 and positively charged residues of Cyclin T1 drive the complex formation that is confirmed by mutagenesis data on Hexim1 mediated transcription regulation in cells. Thus, our studies provide structural insights how Hexim1 recognizes the Cyclin T1 subunit of P-TEFb, which is a key step toward the regulation of transcription elongation. PMID- 17724344 TI - Feeling the heat: ground squirrels heat their tails to discourage rattlesnake attack. PMID- 17724343 TI - Spatial regulation of Raf kinase signaling by RKTG. AB - Subcellular compartmentalization has become an important theme in cell signaling such as spatial regulation of Ras by RasGRP1 and MEK/ERK by Sef. Here, we report spatial regulation of Raf kinase by RKTG (Raf kinase trapping to Golgi). RKTG is a seven-transmembrane protein localized at the Golgi apparatus. RKTG expression inhibits EGF-stimulated ERK and RSK phosphorylation, blocks NGF-mediated PC12 cell differentiation, and antagonizes Ras- and Raf-1-stimulated Elk-1 transactivation. Through interaction with Raf-1, RKTG changes the localization of Raf-1 from cytoplasm to the Golgi apparatus, blocks EGF-stimulated Raf-1 membrane translocation, and reduces the interaction of Raf-1 with Ras and MEK1. In RKTG null mice, the basal ERK phosphorylation level is increased in the brain and liver. In RKTG-deleted mouse embryonic fibroblasts, EGF-induced ERK phosphorylation is enhanced. Collectively, our results reveal a paradigm of spatial regulation of Raf kinase by RKTG via sequestrating Raf-1 to the Golgi apparatus and thereby inhibiting the ERK signaling pathway. PMID- 17724345 TI - The synthesis and in vitro testing of a zinc-activated MRI contrast agent. AB - Zinc(II) plays a vital role in normal cellular function as an essential component of numerous enzymes, transcription factors, and synaptic vesicles. While zinc can be linked to a variety of physiological processes, the mechanisms of its cellular actions are less discernible. Here, we have synthesized and tested a Zn(II) activated magnetic resonance imaging (MRI) contrast agent in which the coordination geometry of the complex rearranges upon binding of Zn(II). In the absence of Zn(II) water is restricted from binding to a chelated Gd(III) ion by coordinating acetate arms resulting in a low relaxivity of 2.33 mM(-1) x s(-1) at 60 MHz. Upon addition of Zn(II) the relaxivity of the Gd(III)-Zn(II) complex increases to 5.07 mM(-1) x s(-1) and is consistent with one water molecule bound to Gd(III). These results were confirmed by nuclear magnetic relaxation dispersion analysis. There was no observed change in relaxivity of the Gd(III) complex when physiologically competing cations Ca(II) and Mg(II) were added. A competitive binding assay gave a dissociation constant of 2.38 x 10(-4) M for the Gd(III)-Zn(II) complex. In vitro magnetic resonance images confirm that Zn(II) concentrations as low as 100 microM can be detected by using this contrast agent. PMID- 17724347 TI - Single nucleotide polymorphisms in the NOD2/CARD15 gene are associated with an increased risk of relapse and death for patients with acute leukemia after hematopoietic stem-cell transplantation with unrelated donors. AB - PURPOSE: Hematopoietic stem cell transplantation (HSCT) is an important option in the management of acute leukemia, but the risk of disease relapse and death remains appreciable. Recent studies have suggested that nucleotide-binding oligomerization domain 2 (NOD2)/caspase recruitment domain 15 (CARD15) gene single nucleotide polymorphisms (SNPs), implicated in innate immunity and Crohn's disease, may also affect immune function post-HSCT. PATIENTS AND METHODS: NOD2/CARD15 genotypes were analyzed in 196 patients diagnosed with acute leukemia and their unrelated donors. The pairs are part of a previously well-characterized cohort with a median follow-up of 2.2 years (range, 0.42 to 6.61 years). T-cell depletion was used in 83% of pairs. RESULTS: NOD2/CARD15 SNPs were associated with a reduction in overall survival (44% v 22%; log-rank P = .0087) due to an increase in disease relapse (32% v 54%; Gray's test P = .001) as compared with wild-type pairs. In multivariate analyses, the two most significant factors impacting outcome were transplantation in relapse and the presence of SNPs. The incidence of acute graft-versus-host disease was low and there was no significant difference due to the presence of SNPs. CONCLUSION: These data indicate an unrecognized role for the NOD2/CARD15 gene in unrelated donor HSCT for acute leukemia. The increased risk of disease relapse suggests that the wild-type gene product may contribute to a graft-versus-leukemia effect. These data suggest that NOD2/CARD15 genotyping before transplantation may contribute to prognosis and influence clinical management. PMID- 17724346 TI - Synergism of Bacillus thuringiensis toxins by a fragment of a toxin-binding cadherin. AB - The insecticidal crystal proteins produced by Bacillus thuringiensis (Bt) are broadly used to control insect pests with agricultural importance. The cadherin Bt-R(1) is a binding protein for Bt Cry1A toxins in midgut epithelia of tobacco hornworm (Manduca sexta). We previously identified the Bt-R(1) region most proximal to the cell membrane (CR12-MPED) as the essential binding region required for Cry1Ab-mediated cytotoxicity. Here, we report that a peptide containing this region expressed in Escherichia coli functions as a synergist of Cry1A toxicity against lepidopteran larvae. Far-UV circular dichroism and (1)H NMR spectroscopy confirmed that our purified CR12-MPED peptide mainly consisted of beta-strands and random coils with unfolded structure. CR12-MPED peptide bound brush border membrane vesicles with high affinity (K(d) = 32 nM) and insect midgut microvilli but did not alter Cry1Ab or Cry1Ac binding localization in the midgut. By BIAcore analysis we demonstrate that Cry1Ab binds CR12-MPED at high (9 nM)- and low (1 microM)-affinity sites. CR12-MPED-mediated Cry1A toxicity enhancement was significantly reduced when the high-affinity Cry1A-binding epitope ((1416)GVLTLNIQ(1423)) within the peptide was altered. Because the mixtures of low Bt toxin dose and CR12-MPED peptide effectively control target insect pests, our discovery has important implications related to the use of this peptide to enhance insecticidal activity of Bt toxin-based biopesticides and transgenic Bt crops. PMID- 17724348 TI - Concept of optimal surgical cytoreduction in advanced ovarian cancer: a brief critique and a call for action. PMID- 17724349 TI - Comorbidity and disease status based risk stratification of outcomes among patients with acute myeloid leukemia or myelodysplasia receiving allogeneic hematopoietic cell transplantation. AB - PURPOSE: Retrospective studies have shown similar survival among patients with acute myeloid leukemia (AML) and myelodysplasia (MDS) after nonmyeloablative compared with myeloablative conditioning. Refined risk stratification is required to design prospective trials. PATIENTS AND METHODS: We stratified outcomes among patients with AML (n = 391) or MDS (n = 186) who received either nonmyeloablative (n = 125) or myeloablative (n = 452) allogeneic hematopoietic cell transplantation (HCT) based on comorbidities, as assessed by a HCT-specific comorbidity index (HCT-CI), as well as disease status. Patients receiving nonmyeloablative conditioning were older, more frequently pretreated, more often received unrelated grafts, and more often had HCT-CI scores of 3 compared with patients who received myeloablative conditioning. RESULTS: Patients with HCT-CI scores of 0 to 2 and either low or high disease risks had probabilities of overall survival at 2 years of 70% and 57% after nonmyeloablative conditioning compared with 78% and 50% after myeloablative conditioning, respectively. Patients with HCT-CI scores of 3 and either low or high disease risks had probabilities of overall survival of 41% and 29% with nonmyeloablative conditioning compared with 45% and 24% with myeloablative regimens, respectively. After adjusting for pretransplantation differences, stratified outcomes were not significantly different among patients receiving nonmyeloablative compared with myeloablative conditioning, with the exception of lessened nonrelapse mortality (hazard ratio, 0.50; P = .05) in the highest risk group. CONCLUSION: Patients with low comorbidity scores could be candidates for prospective randomized trials comparing nonmyeloablative and myeloablative conditioning regardless of disease status. Additional data are required for patients with low-risk diseases and high comorbidity scores. Novel antitumor agents combined with nonmyeloablative HCT should be explored among patients with high comorbidity scores and advanced disease. PMID- 17724350 TI - Raloxifene examined for breast cancer prevention. PMID- 17724352 TI - Personal medication record campaigns get underway. PMID- 17724353 TI - Government's new pricing methods put squeeze on pharmacies. PMID- 17724354 TI - Patient care interventions by pharmacy students in the intensive care unit. PMID- 17724355 TI - Questionable conclusions about epoetin alfa. PMID- 17724358 TI - Pharmacist's intervention for older hospitalized patients. PMID- 17724359 TI - Improving emergency care for victims of sexual offense. PMID- 17724360 TI - Lenalidomide in the treatment of multiple myeloma. AB - PURPOSE: The pharmacology, clinical use, adverse effects, dosage and administration, and cost of lenalidomide in the treatment of multiple myeloma (MM) are reviewed. SUMMARY: Lenalidomide is an analogue of thalidomide and has been shown to be more potent than thalidomide in the stimulation of T-cell, interleukin-2, and interferon-gamma production. Both drugs have direct cytotoxic effects on myeloma cells and are capable of inducing apoptosis. They are also capable of reducing angiogenesis through the inhibition of the secretion of vascular endothelial growth factor (VEGF). Inhibition of VEGF leads to alterations in the microvasculature of the bone marrow environment and inhibits myeloma cell growth and proliferation. Unlike thalidomide, lenalidomide has almost no sedative or constipative properties and induces only minimal neurotoxicity; however, there is concern about lenalidomide's teratogenic potential. Phase I, II, and III trials have been carried out with lenalidomide in patients with relapsed or refractory MM, and the drug has shown impressive response rates in relapsed disease. The combination of lenalidomide and dexamethasone has shown superior patient survival. Lenalidomide's efficacy in newly diagnosed MM is currently being studied. Neutropenia and thrombocytopenia were found to be the most common grade 3 or higher toxicities. Rates of these toxicities varied among trials and may have been affected by the setting in which lenalidomide was used (i.e., relapsed or refractory disease versus newly diagnosed MM). CONCLUSION: Lenalidomide, a thalidomide analogue, has produced good results when used with dexamethasone in patients with relapsed or refractory MM. Lenalidomide is associated with hematologic toxicities, and participation in a restricted-distribution program is required of prescribers, pharmacies, and patients because of the drug's teratogenic potential. PMID- 17724361 TI - Dosing factor VIIa (recombinant) in nonhemophiliac patients with bleeding after cardiac surgery. AB - PURPOSE: The dosing of factor VIIa (recombinant) in nonhemophiliac patients with cardiac-surgery-associated bleeding (CSAB) is discussed. SUMMARY: Factor VIIa (recombinant) is a vitamin K-dependent glycoprotein that is FDA-approved for use in patients with hemophilia A or B with inhibitors to factor VIII or IX and for patients with factor VII deficiency. Case reports and observational studies indicate that factor VIIa (recombinant) may be efficacious for the treatment of acute bleeding episodes related to trauma, surgery, and coagulopathies. The use of factor VIIa (recombinant) for CSAB is increasing. No controlled clinical trials have been conducted to determine the safety and efficacy of factor VIIa (recombinant) in the treatment of CSAB; therefore, the appropriate dosing scheme remains unclear. In addition, thromboembolic events associated with factor VIIa (recombinant) have been reported, so the safety of factor VIIa (recombinant) in patients with normal coagulation systems is unclear. Data from one randomized, controlled, clinical trial of the use of factor VIIa (recombinant) in intracerebral hemorrhage showed a dose-related trend toward adverse events when factor VIIa (recombinant) was compared with placebo. CONCLUSION: No particular dose of factor VIIa (recombinant) is strongly supported in the literature for off label use, and thromboembolic events may be dose dependent. Use of the smallest possible dose is warranted because of the high cost of factor VIIa (recombinant) and the potential for thromboembolic events. A single dose of 2.4 or 4.8 mg or 45 microg/kg should be considered. PMID- 17724362 TI - Elevated serum transaminase levels resulting from concomitant use of rosuvastatin and amiodarone. AB - PURPOSE: The case of a patient whose serum transaminase levels became elevated after concomitant use of rosuvastatin and amiodarone is described. SUMMARY: A 73 year-old white woman with a medical history of diabetes mellitus, hypertension, hypothyroidism, hyperlipidemia, and aortic stenosis reported to a clinic on February 9, 2006. Laboratory tests revealed the following values: total cholesterol, 172 mg/dL; low-density-lipoprotein cholesterol, 96 mg/dL; high density-lipoprotein cholesterol, 55 mg/dL; triglycerides, 105 mg/dL; aspartate transaminase (AST), 14 IU/L; alanine transaminase (ALT), 13 IU/L; alkaline phosphatase (ALP), 68 IU/L; and serum creatinine (SCr), 1.1 mg/dL. At this time, rosuvastatin 5 mg daily was initiated. On April 20, 2006, laboratory tests revealed an AST of 30 IU/L, ALT of 58 IU/L, ALP of 99 IU/L, and SCr of 1.0 mg/dL. Because of the severity of her aortic stenosis, the patient underwent aortic valve replacement on May 15, 2006, and amiodarone was initiated. Laboratory tests completed on May 31, 2006, revealed an AST of 192 IU/L, ALT of 336 IU/L, ALP of 322 IU/L, and SCr of 1.1 mg/dL. She did not report any symptoms of myopathy or liver dysfunction. Ultrasound revealed no liver abnormalities. The rosuvastatin was discontinued because of a potential interaction with the amiodarone. One week after the rosuvastatin was stopped, her laboratory tests showed an AST of 68 IU/L, an ALT of 126 IU/L, an ALP of 292 IU/L, a creatine kinase concentration of 22 IU/L, and an SCr of 1.0 mg/dL. Two months later, her liver function test values had continued to decline. CONCLUSION: A potential interaction between rosuvastatin and amiodarone resulted in asymptomatic elevation of serum transaminase levels in a 73-year-old woman. PMID- 17724363 TI - Comparative tolerability of 2- and 15-minute intravenous infusions of pantoprazole. AB - PURPOSE: The safety and tolerability of 80 mg i.v. pantoprazole administered as a 2-minute versus a 15-minute infusion were studied. METHODS: In a single-blind, randomized, multiple-dose, parallel-group study, 48 healthy participants (ages 18 45 years) were randomly assigned for treatment with 80 mg i.v. pantoprazole infused for 2 or 15 minutes once daily for seven days. A blinded evaluator assessed the injection site for phlebitis and infiltration on a 5-point scale at specified intervals. Participants completed the visual analogue scale (VAS) for pain and burning at baseline and at 5 minutes postinjection. RESULTS: More than 99% of the preinfusion and postinfusion infiltration scores and >95% of the phlebitis scores were rated as zero in 48 healthy participants. A total of 7 infiltration scores (1%) and 72 postinfusion phlebitis scores (5%) of greater than 0 were recorded, all of which were mild in nature. Forty-one phlebitis scores of 1 and 1 score of 2 were from 12 participants in the 2-minute group, and 20 scores of 1 and 10 scores of 2 were from 8 participants in the 15-minute group. VAS assessments showed that the perception of pain and burning was not greater in the 2-minute group. There were no significant differences in adverse events between the two groups. CONCLUSION: The safety and tolerability profiles of i.v. pantoprazole administered as a 2-minute infusion were similar to those of the 15-minute infusion. This protocol may result in the savings of staff time with no additional discomfort to the patient. PMID- 17724364 TI - Analysis of pharmacist charges for medication therapy management services in an outpatient setting. AB - PURPOSE: Pharmacist charges for medication therapy management (MTM) services in an outpatient setting were analyzed. METHODS: Patients' visits with pharmacists in three ambulatory care clinics in a large, urban teaching institution from December 2005 through February 2006 were analyzed. Data collected included the number and type of current diseases, insurance coverage, number of medications patients were taking, pharmacist time spent per patient visit, pharmacy services provided, and estimated charge for services based on level of care provided using physician and pharmacist billing codes. Data were analyzed using descriptive statistics. RESULTS: A total of 500 pharmacist-patient visits were evaluated. The mean +/- S.D. patient age was 59.0 +/- 13.3 years. Patients had a mean +/- S.D. of 4.0 +/- 2.0 diseases and were taking 9.1 +/- 4.6 medications. The majority of visits (83%) lasted 30 minutes or less. The mean charge per visit using incident to physician care billing was $37.09 and $63.24 for level 1 and level 2 visits, respectively. Pharmacist billing was found to result in an average charge of $26.58 ($1 per minute), $53.16 ($2 per minute), or $79.72 ($3 per minute) per visit. There was no difference in pharmacist time spent with complex patients versus noncomplex patients ( p = 0.1314). The use of pharmacist billing codes would not be beneficial unless each visit was billed as $3 per minute. CONCLUSION: Converting from incident-to physician billing to pharmacist billing would not generate additional revenue for this medical center at this time. PMID- 17724365 TI - Effect of a robotic prescription-filling system on pharmacy staff activities and prescription-filling time. AB - PURPOSE: The effects of using an automated prescription-filling system, the ScriptPro SP-200, in an independent pharmacy were evaluated. METHODS: The study was conducted at Punches Pharmacy Plus, an independent pharmacy located in Clare, Michigan. The study design was a preinstallation and postinstallation assessment of the ScriptPro SP-200 automated prescription-filling system. Videotaping and work sampling techniques were used to collect the preinstallation and postinstallation data of the ScriptPro SP-200. The use of the pharmacy staff and the time spent in direct and indirect prescription- filling activities, such as receiving, order entry, filling, inspecting, packaging, dispensing, phone calls, and inventory management, were measured and compared preinstallation and postinstallation. RESULTS: With the installation of automation, the percentage of time spent by the pharmacy staff significantly changed (p < 0.001). Meanwhile, there was a statistically significant difference in terms of the percentages of time spent on various activities between the preinstallation and postinstallation of automation (p < 0.001). Before installation of automation, the direct and indirect prescription-filling times used were 6.07 and 2.11 minutes, respectively, to fill one prescription. Analyses of the average time spent per prescription showed that the installation of automation could save nearly 0.22 minute per prescription, especially filling time per prescription-which was significantly decreased from 2.63 to 2.07 minutes with an average of 0.56 minute saved (p < 0.05). CONCLUSION: An automated system reduced prescription-filling time but required staffing adjustments to optimize the efficiency gained. PMID- 17724366 TI - Admissions to a medical intensive care unit related to adverse drug reactions. AB - PURPOSE: The frequency, severity, and preventability of adverse drug reactions (ADRs) leading to admission in a medical intensive care unit (MICU) were studied. METHODS: A prospective consecutive 19-week observational study was conducted between December 2004 and May 2005 in the department of critical care medicine at a tertiary care teaching hospital. Patients admitted to the MICU because of an ADR were followed prospectively until hospital discharge or death. The causality, severity, and preventability of each ADR were determined. Duration of MICU stay and overall duration of hospital stay were also assessed. RESULTS: A total of 281 patients were admitted to the MICU over the 19-week study period. Of these, 21 (7.5%) admissions were ADR related. Of the 21 ADRs analyzed, 3 (14%) were moderate, 14 (67%) were severe, and 4 (19%) were fatal. A total of 18 ADRs (86%) were deemed preventable. Drug interactions were the cause of 12 ADRs (57%), 100% of which were preventable. Aspirin was the most commonly implicated medication (28.6%). Bleeding was the most common ADR admission diagnosis (gastrointestinal bleeding accounted for 33% of all ADRs). ADR-related admissions resulted in an additional 119 total days of MICU stay and an additional 114 days of medical ward stay. CONCLUSION: The majority of the ADRs for which patients were admitted to an MICU were deemed preventable. Bleeding caused by some combination of nonsteroidal antiinflammatory drugs (NSAIDs), cyclooxygenase-2-selective NSAIDS, aspirin, and clopidogrel was the most common reason for ADR-related MICU admissions. PMID- 17724367 TI - Emergency department care for victims of sexual offense. AB - PURPOSE: Emergency department (ED) care for sexual offense victims was studied and compared with national treatment guidelines. METHODS: This retrospective study analyzed data from the 2003 National Hospital Ambulatory Medical Care Survey. ED visits were selected based on the reason for the patient's visit, diagnosis, and cause of visit. ED visits were evaluated as two subgroups: rape or sexual assault and molestation or other sexual offense. Data were analyzed to determine whether certain screening procedures were performed, including pregnancy testing, HIV serology testing, urinalysis, cervical or urethral culture, and urine culture. Medication codes for each patient visit were examined to determine if antibiotics, antiretrovirals, emergency contraceptives, anxiolytics, analgesics, or antiemetics were provided. RESULTS: In 2003, there were 251,762 ED visits for a sexual offense; 179,149 of these were for sexual assault or rape and 72,613 for molestation or other sexual offense. Nearly 70% of visits did not involve the prescribing of antibiotic therapy, and during only 6.7% of visits was appropriate antibiotic prophylaxis, as recommended by the Centers for Disease Control and Prevention, provided. For female victims age 12 years or older, pregnancy tests were performed during 36.7% of visits for sexual assault or rape and 6.7% of visits for molestation or other sex crimes. Only 13% of sexual assault or rape victims received HIV serology testing. Sufficient care was provided during only 20.4% of all visits for sexual offense victims. CONCLUSION: The majority of victims of a sexual offense in the United States in 2003 did not receive sufficient care in the ED in accordance with national treatment guidelines. PMID- 17724368 TI - Clinical documentation for patient care: models, concepts, and liability considerations for pharmacists. AB - PURPOSE: A guide to the appropriate documentation of the critical aspects of the patient medical record to ensure reimbursement and the reduction of medical liability is presented. SUMMARY: Several documentation styles can be adopted to record pharmacist interventions, including unstructured notes, semistructured notes, and systematic notes. Documentation should be clear, concise, legible, nonjudgmental, patient focused, and standardized, and it should ensure patient confidentiality. Systematic documentation styles include SOAP (subjective, objective, assessment, plan), TITRS (title, introduction, text, recommendation, signature), and FARM (findings, assessment, recommendations or resolutions, management). SOAP is the primary form for which payers traditionally reimburse. Systematic documentation should be used to demonstrate how pharmacist interventions improved patient care and should not just be used for reimbursement. Pharmacists have the opportunity to build a collaborative relationship with other professionals and with patients. Documentation can provide evidence of this symbiotic relationship where the pharmacist assists in providing a caring and compassionate environment for the patient's benefit. Professional liability, as it relates to clinical documentation, can be an issue. Documentation provides the necessary information to successfully manage the process of discovery and the review of the conduct of all parties involved in a liability issue. CONCLUSION: Documentation in a universal format allows for communication among health care practitioners. Written documentation is one key to a successful, open-communication partnership among providers. In addition, accurate, appropriate, and concise documentation is an essential component of ensuring that the patient care provided is evident, not only for patient safety and continuity but also for cases where reimbursement and quality of care are being challenged contractually or legally. PMID- 17724369 TI - Developing dashboards to measure and manage inpatient pharmacy costs. AB - PURPOSE: A pharmacy dashboard was developed and implemented to identify trends in drug use; normalize data for patient volumes; allow the user to determine whether changes were due to cost increases, actual use changes, or both; permit evaluation of drug use within key diagnoses for individual services; and allow multiple formats and layers of analysis. SUMMARY: At the University of Michigan, a drug cost and drug-use database had been developed, and an enterprise data warehouse had been implemented. The data warehouse served as the core data source for the pharmacy dashboard effort. The department of pharmacy services worked with the clinical information and decision support services (CIDSS) unit to develop and promote the use of the pharmacy dashboard. On the basis of the core data in the data warehouse, the dashboard was designed to harness these data for the useful and actionable presentation to service chiefs, individual house officers, and administration for a better understanding of drug costs and use within the institution. In addition to the drug cost and drug-use trend data, the dashboard included help features such as access to the Drugdex database for detailed clinical information about specific drugs, including indications, adverse effects, and drug interactions. CONCLUSION: The cost reports that were developed through the collaboration between the CIDSS and the department of pharmacy services have permitted a more robust understanding of drug-use trends by a wider audience of physician leaders and clinical pharmacists at the institution. These data are critical in formulating strategies to control drug expenses by each service. PMID- 17724370 TI - Genome-wide detection of testis- and testicular cancer-specific alternative splicing. AB - Alternative pre-messenger RNA (mRNA) splicing is a key molecular event that allows for protein diversity and plays important roles in development and disease. Alternative pre-mRNA splicing regulations during spermatogenesis and alternative pre-mRNA splicing etiology in testicular tumorigenesis are yet to be characterized. By genome-wide analysis, here we describe alternative splicing features that distinguish distinctive patterns of alternative pre-mRNA splicing among human testis, testicular cancer and mouse testis. Through computationally subtractive analysis, we detected 80 testis-specific transcript candidates in human testis, 175 in human testicular cancer and 262 in mouse testis, which were integrated into a database. Reverse transcription-polymerase chain reaction confirmed that most of these transcript candidates from mouse testis were testis specific. Around 40% of the transcripts were from unknown/hypothetical genes, which were useful for further functional analysis. These transcripts were not overlapped, indicating lack of evolutionary conservation. Further chromosome mapping showed distinct chromosomal preference of alternative pre-mRNA splicing events. Comparison analysis indicated that alternative pre-mRNA splicing in human testicular tumor shared some characters/trends with those in mouse testis. Moreover, human testicular tumor tended to use rare splice sites and there were also distinct sequences adjacent dominant splice sites between normal testis and testicular tumor. These special features of alternative pre-mRNA splicing in human testicular tumor suggested that testicular tumorigenesis was involved in multiple steps/levels of alternative splicing events. Using alternative splicing as a potential source for new clinical diagnostic, prognostic and therapeutic strategies for treatment of testicular tumors seems to have a bright prospect. PMID- 17724371 TI - Evaluation of oxidative stress in a group of adolescents exposed to a high level of aflatoxin B1--a multi-center and multi-biomarker study. AB - The association between aflatoxin B1 (AFB1) exposure and oxidative stress was extensively examined in 84 adolescents from an area at high risk for hepatocellular carcinoma in China. Plasma level of aflatoxin B1-albumin adducts (AAAs) was associated with AFB1 excretion in urine (r = 0.394, P < 0.001). Urinary AFB1 was also associated with both the urinary excretion of 8 hydroxydeoxyguanosine (8-OHdG) (r > or = 0.479, P < 0.001) and 8-OHdG and hOGG1 levels in peripheral leukocytes (r > or = 0.308, P < or = 0.005). Similarly, AAA was significantly associated with both the urinary excretion of 8-OHdG (r > or = 0.259, P < or = 0.018) and the 8-OHdG and hOGG1 levels in peripheral leukocytes (r > or = 0.313, P < or = 0.004). In addition, urinary 8-OHdG was correlated with both the level of DNA 8-OHdG (r > or = 0.24, P < or = 0.05) and the expression of hOGG1 in peripheral leukocytes (r > or = 0.429, P < 0.001). Protein carbonyl content (PCC) level was significantly associated with not only the level of DNA 8 OHdG (r > or = 0.366, P < 0.001) and the urinary 8-OHdG (r > or = 0.258, P < or = 0.018) but also the expression of hOGG1 in peripheral leukocytes (r = 0.485, P < 0.001). A significant but weak association was found between high-performance liquid chromatograph-electrochemical detection (HPLC-ECD) and enzyme-linked immunosorbent assay (ELISA) for urinary 8-OHdG (r = 0.334, P = 0.002) and between HPLC-ECD and flow cytometry assays for 8-OHdG in leucocytes (r = 0.395, P < 0.001). Significant associations were observed between AAA and PCC and liver function indices (alanine aminotransferase and aspartate aminotransferase). These findings suggest significant contribution from AFB1 exposure to oxidative stress and subsequent repair among adolescents that may impose substantial risk for hepatocarcinogenesis in adulthood in this region. PMID- 17724372 TI - IGF-1 and IGFBP-3 gene variants influence on serum levels and prostate cancer risk in African-Americans. AB - Insulin-like growth factor (IGF)-1 and Insulin-like growth factor binding protein 3 (IGFBP-3) are strong inhibitors of apoptosis and play a role in mediating the effects of growth hormone. Both IGF-1 and IGFBP-3 serum levels have been linked to cancer risk. Here, we explore the relationship between three common IGF polymorphisms [C/T single-nucleotide polymorphism (SNP) (rs7965399) and a dinucleotide repeat (CA)n within the 5' regulatory region of the IGF-1 gene and the -202 A/C SNP in the IGFBP-3 gene], serum levels and prostate cancer (Pca) risk in 767 African-Americans enrolled in a clinic-based case-control study. IGF 1 and IGFBP-3 levels were measured using immunochemiluminometric assay and the three polymorphisms were typed for 401 Pca cases and 366 age- and ethnicity matched controls. Multiple linear regression and multivariable unconditional logistic regression were used to test for associations between genotypes and circulating IGF levels and Pca risk, respectively. The presence of at least one copy of the IGFBP-3 -202 C allele was strongly associated with lower IGFBP-3 serum levels (3532 versus 3106 ng/ml; P = 0.008). We also observed a 2-fold increase in Pca risk for individuals homozygous for the IGFBP-3 -202 C allele [odds ratio = 2.4; 95% confidence interval = 1.2-4.8). Furthermore, IGF-1 (CA)19 genotypes were significantly associated with lower IGFBP-3 serum levels (P = 0.003). Our results reveal that variation in the 5'-untranslated region of the IGF-1 and IGFBP-3 genes may be influencing IGF serum levels and Pca risk in African-Americans and suggest a need to explore this variation across diverse populations. Our study adds clarity and further support to the previous findings, implicating serum IGFBP-3 levels and the IGFBP-3 -202 A/C SNP in prostate carcinogenesis. PMID- 17724373 TI - 2-cyano-lup-1-en-3-oxo-20-oic acid, a cyano derivative of betulinic acid, activates peroxisome proliferator-activated receptor gamma in colon and pancreatic cancer cells. AB - Betulinic acid (BA) is a phytochemical triterpenoid acid from bark extracts and is cytotoxic to cancer cells and tumors. We modified the A-ring of BA to give a 2 cyano-1-en-3-one moiety and the effects of the 2-cyano-lup-1-en-3-oxo-20-oic acid (CN-BA), 2-cyano derivative of BA, and its methyl ester (CN-BA-Me) were investigated in colon and pancreatic cancer cells. Both CN-BA and CN-BA-Me were highly cytotoxic to Panc-28 pancreatic and SW480 colon cancer cells. CN-BA and CN BA-Me also induced differentiation in 3T3-L1 adipocytes, which exhibited a characteristic fat droplet accumulation induced by peroxisome proliferator activated receptor gamma (PPARgamma) agonists. Based on these results, we investigated the activities of CN-BA and CN-BA-Me as PPARgamma agonists using several receptor-mediated responses including activation of transfected PPARgamma responsive constructs, induction of p21 in Panc-28 cells and induction of caveolin-1 and Kruppel-like factor 4 in colon cancer cells. The results clearly demonstrated that both CN-BA and CN-BA-Me activated PPARgamma-dependent responses in colon (caveolin-1) and pancreatic (p21) cancer cells, whereas induction of KLF4 by these compounds in colon cancer cells was PPARgamma independent and also dependent on cell context. The PPARgamma agonist activities of CN-BA and CN-BA-Me were structure-, response/gene- and cell context-dependent suggesting that these compounds are a novel class of selective PPARgamma modulators with potential for clinical treatment of colon and pancreatic cancer. PMID- 17724374 TI - Biotransformation and transport of the tobacco-specific carcinogen 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in bile duct-cannulated wild type and Mrp2/Abcc2-deficient (TR ) Wistar rats. AB - The role of uptake and efflux transport proteins in the tissue distribution of the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolites is largely unknown. Carbonyl reduction of NNK results in formation of the carcinogenic 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), which in rats is glucuronidated to the non-toxic NNAL-O-glucuronide. Previous in vitro studies showed that NNAL-O-glucuronide is a substrate for the human ATP-binding cassette transport proteins multidrug resistance protein (MRP)1 (ABCC1) and MRP2 (ABCC2). To investigate the influence of Mrp2 deficiency on NNK biotransformation and biliary excretion, [(3)H]NNK was administered intravenously to bile duct-cannulated wild-type (WT) and Mrp2-deficient (TR(-)) Wistar rats; plasma, bile and urine samples were collected for 5 h and analyzed by high pressure liquid chromatography with radiochemical detection. The total radioactivity recovered in WT and TR(-) bile was 12 and 7% of the dose, respectively. NNAL-O-glucuronide accounted for 87% of the radioactivity in WT bile but was not detected in TR(-) bile. Urinary recovery of 1-(3-pyridyl)-1 butanol-4-carboxylic acid (hydroxy acid), NNAL-O-glucuronide and NNAL-N-oxide from 2-5 h was greater in TR(-) compared with WT rats. NNK plasma clearance was significantly higher in TR(-) (115 +/- 23 ml/min/kg) compared with WT (48 +/- 13 ml/min/kg) rats. A higher concentration and/or earlier appearance of hydroxy and 1-(3-pyridyl)-1-butanone-4-carboxylic acids, NNAL-N-oxide and NNK-N-oxide, and decreased NNK and NNAL concentrations in TR(-) plasma suggested increased cytochrome P450 biotransformation in TR(-) rats. The total recovery of hydroxy acid in bile and urine was significantly higher in TR(-) compared with WT rats. Thus, Mrp2 is responsible for the biliary excretion of NNAL-O-glucuronide and Mrp2 deficiency results in increased formation of carcinogenic NNK metabolites. PMID- 17724375 TI - Rapid reversal of interleukin-6-dependent epithelial invasion in a mouse model of microbially induced colon carcinoma. AB - Chronic inflammation of mucosal surfaces renders them increasingly susceptible to epithelial cancers both in humans and mice. We have previously shown that anti inflammatory CD4(+)CD45RB(lo)CD25(+) regulatory (Treg or T(R)) lymphocytes down regulate inflammation and block development of bacteria-triggered colitis and colorectal cancer (CRC) in 129/SvEv Rag2-/- mice. Interestingly, T(R) cells collected from Interleukin (IL)-10-deficient cell donors not only failed to suppress carcinogenesis but instead promoted invasive mucinous colonic carcinoma with a strong gender bias expressing in male mice. We found we show that peritoneal invasion in this model is dependent on pleiotropic cytokine IL-6. Mucinous carcinoma arose rapidly and consistently after treatment with IL10-/- T(R) cells, which were found to express Foxp3+ and localize throughout tumor tissue. Carcinogenesis was rapidly reversible with transfer of wild type IL10 competent T(R) cells. Likewise, treatment with IL10-Ig fusion protein was sufficient to revert the lesions histologically, and restore inflammatory cytokine and oncogene expression to base line levels. These studies indicate an essential role for IL 6 in this CRC phenotype. Furthermore, immune-competent T(R) cells were important not only for preventing pathology but also for constructive remodeling of bowel following tumorigenic microbial insults. These data provide insights into etiopathogenesis of inflammation-associated epithelial invasion and maintenance of epithelial homeostasis. PMID- 17724376 TI - Candidate markers for the detection of hepatocellular carcinoma in low-molecular weight fraction of serum. AB - Hepatocellular carcinoma (HCC) represents an important public health problem in Egypt where up to 90% of HCC cases are attributable to hepatitis C viral (HCV) infection. Serum alpha-fetoprotein is elevated in only approximately 60% of HCC patients. The development of effective markers for the detection of HCC could have an impact on cancer mortality and significant public health implications worldwide. The objective of our study was to assess six candidate markers for detection of HCC identified by mass spectrometric analysis of enriched serum. The study examined 78 HCC cases and 72 age- and gender-matched cancer-free controls recruited from the Egyptian population. Matrix-assisted laser desorption ionization time-of-flight mass spectrometric analysis of enriched low-molecular weight fraction of serum was used for identification of the candidate markers. Our analyses show that all six candidate markers are associated with HCC after adjustment for important covariates including HCV and hepatitis B viral infections. The marker candidates are independently predictive of HCC with areas under the receiver operating characteristic (AuROC) curve ranging from 63-93%. A combination of the six markers improves prediction accuracy to 100% sensitivity, 91% specificity and 98% AuROC curve in an independent test set of 50 patients. Two of the candidate markers were identified by sequencing as fragments of complement C3 and C4. In conclusion, a set of six peptides distinguished with high prediction accuracy HCC from controls in an Egyptian population with a high rate of chronic HCV infection. Further evaluation of these marker candidates for the diagnosis of HCC is needed. PMID- 17724377 TI - Green tea and black tea consumption in relation to colorectal cancer risk: the Singapore Chinese Health Study. AB - The relationships between green tea and black tea consumption and colorectal cancer risk were examined within the Singapore Chinese Health Study, a prospective cohort study of diet and cancer involving >60,000 men and women. Intake of green tea and black tea was assessed through in-person interviews. Incident cancer cases and deaths among cohort members were identified through record linkage of the cohort database with respective databases from the nationwide Singapore Cancer Registry and the Singapore Registry of Births and Deaths. The proportional hazard regression method was used to examine the associations between intake of green and black tea separately and colorectal cancer risk with adjustment for potential confounders. After an average of 8.9 years of follow-up, 845 colorectal cancer cases were identified. Subjects who drank green tea exhibited a statistically non-significant increase in risk [relative risk (RR) = 1.12, 95% confidence interval (CI) = 0.97-1.29] relative to non-drinkers of green tea. This risk increase was mainly confined to men (RR = 1.31, 95% CI = 1.08-1.58); the comparable RR in women was 0.89 (95% CI = 0.71 1.12). In men, the green tea-colorectal cancer association was noted mainly in those with advanced disease (Duke C or D) (RR = 1.53, 95% CI = 1.19-1.97), and the association was dose dependent (P for trend = 0.0002). This latter association was especially strong within the colon subsite (RR = 1.75, 95% CI = 1.24-2.46; P for trend < 0.0001). Irrespective of gender, intake of black tea was not associated with risk of colorectal cancer (RR = 0.92, 95% CI = 0.79-1.07) in this Asian population. PMID- 17724378 TI - Protective role of 17 beta -estradiol against the development of Helicobacter pylori-induced gastric cancer in INS-GAS mice. AB - The incidence of gastric cancer is higher in men than women. Epidemiological studies suggest that female hormones reduce gastric cancer risk. We examined the effect of ovarian-dependent female hormones on Helicobacter pylori-induced gastric cancer in hypergastrinemic INS-GAS mice. Male and female sexually intact or ovariectomized (OVX) mice were inoculated with H.pylori SS1 or vehicle-only at 10 weeks of age, and tissues were evaluated at 16 or 28 weeks post-infection (WPI). A subset of OVX females were supplemented with 17beta-estradiol (E2), beginning at 16 WPI. Stomachs were evaluated by histopathology, Ki-67 proliferation index, H.pylori quantitative culture and quantitative polymerase chain reaction for messenger RNA expression of inducible nitric oxide synthase (iNOS) and inflammatory cytokines. Infected OVX females developed significantly more severe gastritis (P < 0.05) than infected intact females at both time points. E2 treatment in infected OVX females attenuated the severity of gastritis. Gastrointestinal intraepithelial neoplasia (GIN) developed in 42% of infected males and 10% of infected OVX females by 28 WPI, whereas infected intact females and E2-treated OVX females did not develop GIN. Infected OVX females showed significantly increased iNOS expression and epithelial cell proliferation when compared with intact, infected females. Likewise, interferon-gamma, tumor necrosis factor-alpha and interleukin-1beta (IL-1beta) expression in infected OVX females were significantly increased at 28 WPI when compared with intact counterparts. E2 treatment in infected OVX females significantly decreased IL 1beta expression, increased IL-10 expression and reduced epithelial cell proliferation. These results demonstrate a protective effect of E2 in H.pylori induced gastric cancer in a mouse model. PMID- 17724380 TI - Spirituality and health in Punjabi Sikh. AB - The purpose of this study was to examine the interrelationship of health, illness, and spirituality for Punjabi Sikh living in Canada. A grounded theory study with a convenience sample and use of snowballing technique provided a sample of 15 participants ranging in age from 20 to 70 years. Constant comparative method with dimensional analysis was used to analyze the data beginning with the first interview. The themes of being healthy and looking for the spiritual are described. Looking for the spiritual results in the person becoming spiritually strong and therefore being healthier, recovering from illness, or having the ability to feel comfortable when near death. Nurses who understand the interplay of spirituality and health can support Punjabi Sikh in their food requirements, prayers, and feelings of hope and anguish during illness or life transitions. PMID- 17724381 TI - A theoretical framework for using health realization to reduce stress and improve coping in refugee communities. AB - Refugees have faced extraordinarily stressful situations in their past, and many continue to experience stress daily as they cope with the refugee adjustment experience. A strengths-based, community-focused intervention known as Health Realization (HR) is a promising strategy for nurses to promote positive psychological outcomes in these populations. Although similar in some ways to cognitive therapy, the HR intervention emphasizes the role of thought versus the content of thought. It does not promote actively changing intrusive or negative thoughts but rather promotes an understanding that allows a degree of detachment from thoughts--a shift in consciousness that can provide relief and facilitate healing. An adapted stress and coping model provides a theoretical framework to test the effectiveness of using HR with refugees, which in turn provides a solid foundation for research that can support or refute the existing substantial anecdotal evidence for the use of this intervention in holistic nursing practice. PMID- 17724382 TI - The effect of faith or spirituality in pregnancy: a content analysis. AB - This study used a qualitative descriptive research design to discover the relevance and meaning of spirituality in the lives of 130 urban low-income pregnant women by asking the open-ended question, "How does your faith or spirituality affect your pregnancy if at all?" Forty-seven percent of the women in this study described how spirituality affected their pregnancy positively, 45% described that spirituality did not affect them, and 5.4% were unsure. A content analysis of those who answered positively revealed six themes from the data describing the meaning of faith or spirituality in pregnancy: (a) guidance and support; (b) protection, blessing, or reward; (c) communication with God; (d) strength and confidence; (e) help with difficult moral choices; and (f) a generalized positive effect. These findings point to the importance of attending to spirituality as a resource in pregnancy for those who value it and further exploring the meaning of spirituality in pregnancy. PMID- 17724386 TI - Phenomenology: an exploration. AB - Investigators who use phenomenological approaches to understand experiences of human healing, caring, and wholeness need to consider the differences that exist between descriptive and hermeneutic phenomenology. In this article, these two approaches are compared and contrasted with respect to roots, similarities, and differences. Guidelines are offered to assist prospective investigators in selecting the approach most suitable to personal cognitive style and beliefs about the ways humans experience and find meanings during transitions through wellness and illness to advance nursing knowledge in a holistic view. PMID- 17724384 TI - Self-care activities captured through discussion among community-dwelling older adults. AB - Four separate focus group sessions were conducted in the Detroit metropolitan area to invite vital elders to speak freely about their health, health problems, health practices, and how they maintain their bio-psycho-social and spiritual well-being. Twenty-eight participants were interviewed. The majority were African American, female, widowed, Protestant, and had achieved a high school or greater educational level. Field notes and taped interviews were transcribed for data analysis. Together, two raters completed data reduction and coding for theme identification and categorization. A holistic nursing model was used to guide the content analysis. Five themes were revealed that described the context of well being for community-dwelling elders: faith ways, positive energy, support systems, wellness activities, and affirmative self-appraisal. Well-being depended on an awareness of how lifestyle impacted the physical, psychological, social, and spiritual health of each individual. This study lends credence to interventions aimed at promoting holistic health care for community-dwelling elders. PMID- 17724389 TI - The silence of suffering: breaking the sound barriers. AB - Suffering is an inevitable reality that student nurses may be unprepared to witness. The 14-week college course, Understanding Suffering, was developed to help students better understand the suffering experience. Content for the course was drawn from nursing, sociological, and theological perspectives. Students scored significantly higher on a post-course evaluation of empathy and stated they felt better prepared to intervene in difficult clinical situations involving suffering. Course development, assignments, and evaluation are described in the article. PMID- 17724390 TI - Toward easing suffering through reflection. AB - This article is a partially constructed reflective narrative on my practice as a complementary therapist working with Indigo, a dying patient at the hospice, and her family that offers insights into practice and narrative construction. The reflective effort is to appreciate and work toward easing Indigo's suffering. However, this emerges as problematic and invites the reader to dialogue with the text in terms of the readers' own experiences. PMID- 17724391 TI - Alternative method for predicting optimal insertion depth of the laryngeal tube in children. AB - BACKGROUND: Little information is available about the accuracy of the teeth mark on the laryngeal tube (LT) as a guide to correct placement in children. The aim of this crossover study was to evaluate three methods for optimal insertion depth of the size (#) 2 tube in children weighing 12-25 kg. METHOD: In 24 children, the LT #2 was consecutively inserted by three different methods: (A) until the thick teeth mark on the tube was aligned with the upper incisors, (B) until resistance was felt, and (C) by inserting to a depth, previously measured, of the curved distance between the cricoid cartilage and the upper incisor. In each case, the depth of insertion, the degree of effective ventilation, the presence of leakage, and the fibreoptic view were assessed. RESULTS: Insertion based on the teeth mark led to a shorter insertion depth and a greater incidence of inadequate ventilation compared with the other two methods. There was no difference in the adequacy of ventilation between methods B and C. The vocal cords were more easily identified with methods B (62.5%) and C (75%) than with method A (12.5%). CONCLUSIONS: Insertion of the LT #2 aligned with the teeth mark can result in a shallow insertion depth and inadequate ventilation. The measured distance from the cricoid cartilage to the upper incisor offers alternative guidance for correct LT insertion. PMID- 17724392 TI - Motivational factors and physician advice for physical activity in older urban adults. AB - This study aimed to ascertain by means of a new scale older adults' motives for engaging in physical activity, in a probability and representative sample of an older urban population. The sample size was 630 older adults, ranging from 65 to 94 years in age, randomly selected using multistage sampling. The participants completed a 17-item questionnaire, as well as answering questions on demographic variables, type of demand for physical activity, and physician's recommendation. A principal-component analysis was performed. The relationships among the four factors (physical health, social relationships, competence, and physician's advice) show a clearly motivational structure. Significant relationships have also been found between physician's recommendation and type of demand. The findings suggest that programs promoting physical activity in older adults should have different characteristics from those aimed at general adult populations. PMID- 17724393 TI - Physical and psychological outcomes of a supported physical activity program for older carers. AB - This study evaluated health benefits of a supported physical activity program for 116 older carers (mean age 64.4 [SD = 7.9], 85% women). Participants undertook a 6-month center-based physical activity program (strength training, yoga, or Tai Chi). Eighty-eight participants (76%) completed the program. Multivariate repeated-measures ANOVA identified overall significant improvement postintervention (p = .004). Univariate analyses revealed significant improvements for balance, strength, gait endurance, depression, and SF-36 (physical component; p < .05). There was no change in the Zarit Carer Burden Scale (p > .05). Change in performance scores did not differ significantly between those with higher and lower attendance at classes, although there was significantly greater improvement in gait endurance and balance (p < .05) in those attending classes run twice weekly than in those attending once-weekly classes. In conclusion, a carer physical activity program, providing additional carer support to facilitate participation, can achieve high levels of involvement by carers and significant health benefits. PMID- 17724394 TI - Quality of life in the Fourth Age: exercise experiences of nursing home residents. AB - Life in the Fourth Age has been typified as a time of continued functional decline and reduced quality of life. Exercise might positively affect this experience. This study explored the exercise experiences of nursing home residents age 86-99 years who participated in a 6-month exercise intervention. An interpretive phenomenological approach was adopted. Twenty-one interviews were held with 14 residents at baseline and 7 residents at follow-up. Although their expectations were initially conservative, by the end of the intervention participants noted improved quality of life through better mobility, decreased fear of falling, and feelings of achievement and success. They valued the program as an opportunity to do something for themselves, to add something to their weekly routine, to meet other people, and to be more active generally. The professionalism of the exercise instructor appears to have been critical, balancing principles of safe and effective practice with the need to ensure that participants had fun in a supportive environment. PMID- 17724395 TI - Effects of exercise training with weighted vests on bone turnover and isokinetic strength in postmenopausal women. AB - The effects of 12 wk of exercise training using weighted vests on bone turnover and isokinetic strength were evaluated in postmenopausal women randomly assigned as exercisers (EX; n = 9) or controls (CON; n = 7). Training included 3 multimodal exercise sessions per wk wearing weighted vests. The vest load was progressively increased each wk to a maximum of 15% of body weight. Bone turnover was determined from resting levels of serum osteocalcin and NTx. Knee and ankle strength were measured at 60 degrees/s and 180 degrees/s using an isokinetic dynamometer. After 12 wk, NTx decreased by 14.5% (P or = 2.0 for at least 3 weeks or a negative TEE with a normalized ratio range > or = 2.0 or a partial thromboplastin time > 50 seconds at the time of DCC. Immediately after policy implementation, anticoagulation status and TEE results were reviewed in 53 patients (42 men/11 women; ages 21-84 years) and 1 year post-policy implementation. RESULTS: Before policy implementation, 14 of 52 patients (27%) had DCC performed without adequate anticoagulation or a negative TEE. Immediately postimplementation, only 2 of 50 patients (4%) had DCC performed without adequate anticoagulation or a negative TEE (P = .002). One year post-policy implementation, only 4 of 48 patients (8%) had DCC performed without adequate anticoagulation or a negative TEE (P = .03). CONCLUSIONS: Implementing a written policy greatly reduces the number of patients undergoing DCC without adequate anticoagulation or a negative TEE. The impact of this intervention was quickly demonstrable and persisted during follow-up. Supplementing published recommendations with guideline-driven policies may reduce variations in clinical practice and improve quality of care. PMID- 17724427 TI - HIV testing of commercially insured patients diagnosed with sexually transmitted diseases. PMID- 17724428 TI - Voluntary rapid human immunodeficiency virus (HIV) testing in jails. AB - OBJECTIVES: To provide human immunodeficiency virus (HIV) rapid testing to persons in jails, identify previously undiagnosed cases of HIV infection, and refer HIV-infected inmates to care, treatment, and prevention services. DESIGN: Four state health departments (Florida, Louisiana, New York, and Wisconsin) collaborated with jails to implement stand-alone voluntary rapid HIV testing programs. Inmates requested or were referred by medical staff for rapid HIV testing. HIV testing was provided by the health department, correctional facility, or a community-based organization. Inmates whose rapid test was reactive were offered confirmatory testing, medical evaluation, prevention services, and discharge planning. RESULTS: From December 2003 through May 2006, rapid HIV testing was provided to 33,211 inmates, more than 99.9% of whom received their test results. Most of the inmates tested were male (79%), black (58%), and less than 35 years of age (60%). A total of 440 (1.3%) rapid HIV tests were reactive, and 409 (1.2%) of the results were confirmed positive. The testing programs identified 269 (0.8%) previously undiagnosed cases of HIV infection. In the multivariate analyses, new HIV diagnoses were associated with race/ethnicity, report of risky behaviors, and with no report of HIV risk behavior. Almost 40% of diagnoses were for inmates whose only reported risk was heterosexual contact. CONCLUSIONS: Rapid HIV testing in jails identified a considerable number of previously undiagnosed cases of HIV infection. Rapid HIV testing should be available to all inmates, regardless of whether inmates reported HIV risky behaviors. PMID- 17724429 TI - Prognostic value of mortality in emergency department sepsis score, procalcitonin, and C-reactive protein in patients with sepsis at the emergency department. AB - The prognostic value of procalcitonin (PCT) in patients with sepsis at the emergency department (ED) has not been evaluated. We conducted a prospective observational study to compare the prognostic value of PCT on sepsis and compared with a validated score, Mortality in Emergency Department Sepsis (MEDS) score, and C-reactive protein (CRP) in the setting of ED of an urban, university-based medical center. Five hundred twenty-five consecutive adult patients admitted to the ED fulfilling the American College of Clinical Pharmacists/Society of Critical Care Medicine Consensus Conference definition of sepsis were prospectively enrolled. Serum PCT and CRP were evaluated for each patient. Clinical characteristics and laboratory results on ED admission were recorded using a standardized form. Each patient was followed for at least 30 days. The main outcome was early (5-day) and late (6- to 30-day) mortality. The median age of the study sample was 64.0 (interquartile range, 47-76) years old, and the overall 30-day mortality rate was 10.5%. The c-statistic in the prediction of early mortality was 0.89 for MEDS, 0.76 for PCT, and 0.68 for CRP. The c statistic in the prediction of late mortality was 0.78 for MEDS, 0.70 for PCT, and 0.63 for CRP. Overall, MEDS score has the best discriminative capability among the three tested markers. Under the best cutoff value, PCT was the most sensitive, and MEDS score was the most specific marker. We suggest further combining the information on PCT and MEDS score to enhance the accuracy in predicting ED sepsis mortality. PMID- 17724430 TI - Endotoxin pretreatment improves bacterial clearance and decreases mortality in mice challenged with Staphylococcus aureus. AB - We studied the effects of tolerance induced by Escherichia coli-derived LPS on the innate immune response to a subsequent Staphylococcus aureus bacterial challenge. LPS tolerance was induced in wild-type mice by either intraperitoneal or intravenous injection of 2 microg of LPS on 2 consecutive days. Mice were challenged with an intravenous injection of live S. aureus (5 x 10(8) colony forming units) 2 days after the second LPS dose. LPS-tolerant mice had a diminished serum interferon-gamma response to the bacterial challenge. Bacterial counts in liver and spleen tissues were decreased, and survival was improved after the Staphylococcus challenge in LPS-tolerant mice compared with saline pretreated control mice. LPS pretreatment by the intravenous route was also associated with a decreased number of bacterial colonies in lung tissue in addition to liver and spleen, suggesting that induction of LPS tolerance was somewhat compartmentalized after intraperitoneal LPS pretreatment. Induction of tolerance seemed to be due to LPS-specific signaling because LPS pretreatment of LPS-nonresponsive C3H/HeJ mice did not provide similar effects after bacterial challenge. Flow cytometric analysis of spleens from LPS-tolerant mice revealed an increase in phagocytic cells (neutrophiles and macrophages) compared with control mice. Ex vivo culture of splenocytes from LPS-tolerant mice demonstrated increased uptake of fluorescein isothiocyanate-tagged ovalbumin, but no difference in either phagocytosis of fluorescein isothiocyanate-labeled Staphylococcus or bactericidal activity could be demonstrated on a per-cell basis. These results show that attenuation of inflammation and mortality during LPS tolerance extends to gram-positive bacterial organisms and suggests that LPS induced enhancement of the innate immune response may be attributed to increased numbers of phagocytic cells. PMID- 17724431 TI - Heme oxygenase-derived endogenous carbon monoxide impairs flow-induced dilation in resistance vessels. AB - Vascular tissues normally express heat shock protein 32 (heme oxygenase [HO] 1), which degrades heme. A product of this reaction, carbon monoxide (CO), has been shown to promote relaxation of vascular smooth muscle, but it also inhibits NOS. Because flow-induced dilation is dependent upon the formation of endothelium derived NO, we conducted the current study to determine if HO-mediated formation of CO impairs flow-induced dilation. In isolated pressurized first-order gracilis muscle arterioles, proximal and distal pressures were manipulated to generate intraluminal flows of 0 to 50 microL/min at a constant vascular midline pressure of 80 +/- 1 mmHg. Vehicle-treated vessels displayed flow-related vasodilation, which was abolished by a NOS inhibitor, Nomega-nitro-L-arginine methyl ester. Acute intraluminal pretreatment with an inhibitor of HO, chromium mesoporphyrin (CrMP), enhanced flow-induced responses in similarly prepared vessels. In contrast, a substrate for heme formation that drives CO generation, delta aminolevulinic acid, abolished flow-induced dilation in a manner which could be fully prevented and reversed by CrMP. In addition, the HO product biliverdin had no effect on flow-induced dilation, whereas the responses were abolished by exogenous CO. Furthermore, spontaneous generation of CO was measured in isolated vascular segments to confirm that delta-aminolevulinic acid increased carbon formation by 29%, whereas CrMP reduced it by 43%. These data show flow-induced dilation can be impaired by a HO product, and that the impairment was not produced by biliverdin but is mimicked by CO. These results suggest that the HO generated CO attenuates flow-induced dilation in the vasculature and, accordingly, may contribute to vascular dysfunction after injury. PMID- 17724433 TI - Na+/H+ exchange inhibition delays the onset of hypovolemic circulatory shock in pigs. AB - Severe blood loss is a major cause of death occurring within hours of traumatic injury. Na+/H+ exchange (NHE-1) activity is an important determinant of the extent of ischemic myocardial injury. The goal of the present study was to test the hypothesis that NHE-1 inhibition delays the onset of hypovolemic circulatory shock, thereby preventing early death due to severe hemorrhage in pigs. Severe hypovolemia was studied in 16 (25.2 kg) anesthetized male pigs in steps of 10-, 20-, 30-, 40-, and 50-mL kg(-1) blood loss, each in 30-min intervals. Shed blood resuscitation was started 30 min after 50 mL kg(-1) blood loss. The experiment was terminated after 3 h of resuscitation. Eight pigs were used as seline control. Eight pigs received 3 mg kg(-1) benzamide, N-(aminoiminomethyl)-4-[4-(2 furanylcarbonyl)-1-piperazinyl]-3-(methylsulfonyl), methanesulfonate (NHE-1 inhibitor) 15 min before hemorrhage. Seven control pigs died at 40- to 50-mL kg( 1) blood loss. One control pig survived initial resuscitation but died soon after. In contrast, all animals treated with NHE-1 inhibitor survived the entire protocol. In control animals, cardiac output and MAP gradually decreased at each step of blood loss with marked increase in heart rate. Cardiovascular decompensation occurred at 40 mL kg(-1) blood loss. Na+/H+ exchange inhibition increased oxygen delivery, attenuated cardiovascular decompensation, delayed the onset of irreversible hypovolemic circulatory shock, and enabled resuscitation to survival. Echocardiography analysis showed that myocardial hypercontracture gradually developed with each step of blood loss in control animals, but this hypercontracture was attenuated in the animals receiving the NHE-1 inhibitor. We conclude that NHE-1 inhibition attenuates ischemic myocardial hypercontracture, cardiovascular decompensation, delays the onset of hypovolemic circulatory shock, and prevents early death in severe hemorrhage. PMID- 17724432 TI - IL-6 modulates sepsis-induced decreases in transcription of hepatic organic anion and bile acid transporters. AB - Sepsis, a lethal inflammatory syndrome, is characterized by organ system dysfunction. In the liver, we have observed decreased expression of genes encoding proteins modulating key processes. These include organic anion and bile acid transport. We hypothesized that the inflammatory mediator IL-6 modulates altered expression of several key hepatic genes in sepsis via induction of the intracellular transcription factor signal transducer and activator of transcription (Stat) 3. Sepsis was induced in IL-6 +/+ and IL-6 -/- mice, and expression of the liver-restricted genes encoding the sodium-taurocholate cotransporter (Ntcp), the multidrug resistant protein (MRP) 2 and the organic anion transporter protein (OATP), was determined. As demonstrated previously, cecal ligation and puncture decreases expression of Ntcp, MRP-2, and OATP in IL-6 +/+ mice. Transcription elongation analysis demonstrated that altered expression resulted from decreased transcription. These changes were not observed in IL-6 -/ animals. Cecal ligation and puncture increased the DNA binding activity of Stat 3 in IL-6 +/+ but not IL-6 -/- mice. Because the promoters of Ntcp, MRP-2, and OATP do not contain Stat-3 binding sites, we postulated that altered Ntcp, MRP-2, and OATP expression resulted from activation of hepatocyte nuclear factor (HNF) 1alpha, which is IL-6 dependent. Cecal ligation and puncture decreased HNF-1alpha expression and DNA binding activity in IL-6 +/+ but not IL-6 -/- mice. Recombinant human IL-6 restored the sepsis-induced decrease in Ntcp, MRP-2, OATP, and HNF-1alpha expression in IL-6 -/- mice. We conclude that sepsis decreases the expression of three key hepatic genes via a transcriptional mechanism that is IL 6, Stat-3, and HNF-1alpha dependent. PMID- 17724434 TI - Liver X receptor is a key regulator of cytokine release in human monocytes. AB - Aberrant regulation of innate immune responses and uncontrolled cytokine bursts are hallmarks of sepsis and endotoxemia. Activation of the nuclear liver X receptor (LXR) was recently demonstrated to suppress inflammatory genes. Our aim was to investigate the expression of LXR in human monocytes under normal and endotoxemic conditions and to study the influence of LXR activation on endotoxin induced cytokine synthesis and release. Adherent human monocytes or whole blood were pretreated with a synthetic LXR agonist (3-{3-[(2-chloro-3-trifluoromethyl benzyl)-(2,2-diphenyl-ethyl)-amino]-propoxy}-phenyl)-acetic acid) and subsequently challenged with LPS (from Escherichia coli) or peptidoglycan (from Staphylococcus aureus). Cytokine release was assessed by a Multiplex antibody bead kit, and cytokine mRNA levels were measured by real-time reverse transcriptase-polymerase chain reaction. We found that LXRalpha mRNA was up regulated in CD14+ monocytes in LPS-challenged blood, whereas LXRbeta mRNA was not altered. Addition of 3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-(2,2-diphenyl ethyl)-amino]-propoxy}-phenyl)-acetic acid to monocytes suppressed the LPS induced release of IL-1beta, IL-6, IL-8, IL-10, IL-12p40, TMF-alpha, macrophage inflammatory protein 1alpha, macrophage inflammatory protein 1beta, and monocyte chemoattractant protein 1 in a concentration-dependent manner. Surprisingly, an accompanying decrease in cytokine mRNA accumulation was not observed. The suppressed cytokine release could not be explained by a diminished transport of mRNA out of the nucleus or a decreased secretion of cytokines. We propose that LXR is a key regulator of cytokine release in LPS-challenged human monocytes, possibly by interfering with translational events. PMID- 17724435 TI - Cytokine-induced epithelial permeability changes are regulated by the activation of the p38 mitogen-activated protein kinase pathway in cultured Caco-2 cells. AB - Increased intestinal/epithelial permeability in sepsis and endotoxemia has been noted to be induced by proinflammatory cytokines such as interferon-gamma, TNF alpha, and IL-1beta. The p38 mitogen-activated protein kinase (MAPK) signaling pathway plays an important role in regulating the inflammatory response induced by these cytokines. We tested the hypothesis that epithelial permeability changes are regulated through the p38 MAPK signaling pathway. Caco-2 cells were cultured for 21 days and then stimulated with a cytokine mixture (CytoMix: TNF-alpha, interferon-gamma, and IL-1beta). Epithelial barrier function was evaluated by measuring permeability in an Ussing chamber. CytoMix-induced changes of MAPKs (p38, c-Jun amino-terminal kinase, and extracellular-regulated kinase), NO production, and inflammatory responses (IL-6 and IL-8 levels) were also assessed. The signaling pathways were further studied by pretreating cells with SB203580, a specific p38 MAPK inhibitor. CytoMix increased permeability at 24 and 48 h but not at 4 h. This was associated with increased IL-6 and IL-8 production, as well as increases in phosphorylation of all three MAPKs. Treatment with SB203580 completely blocked p38 activity with transient inhibition of p38 phosphorylation. SB203580 also prevented the CytoMix-induced permeability increase and reduced NO, IL-6, and IL-8 levels. The results suggest that p38 MAPK plays an important role in regulating epithelial barrier function during inflammation. PMID- 17724436 TI - Etanercept reduces acute tissue injury and mortality associated to zymosan induced multiple organ dysfunction syndrome. AB - It has been well demonstrated that TNF-alpha is integral to the pathogenesis of multiple organ dysfunction syndrome (MODS). In this study, we investigate the effects of etanercept (10 mg/kg, s.c.), a specific TNF-alpha-soluble inhibitor, on the acute phase and late mortality in a murine model of MODS of nonseptic origin induced by zymosan (500 mg/kg, suspended in saline solution, i.p.). Etanercept was administered 1 h after the injection of zymosan. Animals were killed after 18 h. In another set of experiments, mice were monitored for systemic toxicity, loss of body weight, and mortality for 12 days. Sham-treated and TNF receptor 1 (TNFR1)-deficient animals were used as control. Treatment of mice with Etanercept and TNFR1 gene deletion decreased the peritoneal exudation and the migration of neutrophils caused by zymosan. In addition, pharmacological and genetic neutralization of TNF-alpha attenuated pancreas and ileum injury (histology), the increase in myeloperoxidase activity in the ileum and in the lung, and the formation of TNF-alpha and IL-1beta. Immunohistochemical analysis for TNF-alpha, transforming growth factor beta, and vascular endothelial growth factor revealed a positive staining in pancreas and ileum sections. The degree of immunostaining was markedly reduced after etanercept treatment and in TNFR1 knockout mice. Furthermore, TNF-alpha neutralization decreased the potent apoptotic stimulus induced by zymosan. All of these findings ultimately led to an amelioration of organ functions at 18 h and to a better survival rate at 12 days. Therefore, we demonstrate that etanercept reduces acute tissue injury and mortality associated to MODS of nonseptic origin in mice. PMID- 17724437 TI - Molecular remission of multiple myeloma with cytoreductive autografting followed by a dose-reduced allograft. PMID- 17724438 TI - Late death after unrelated-BMT for dyskeratosis congenita following conditioning with alemtuzumab, fludarabine and melphalan. PMID- 17724439 TI - High-unbound mycophenolic acid concentrations in an infant on peritoneal dialysis following hematopoietic cell transplant. PMID- 17724440 TI - Risk factors for acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: retrospective analysis of 73 patients who received cyclosporin A. AB - Cyclosporin A (CsA) has been used most widely as an immunosuppressive agent for preventing graft-versus-host disease (GVHD). To explore the risk factors including CsA blood levels for grades II-IV acute GVHD, we retrospectively analyzed the data of patients who underwent allogeneic hematopoietic stem cell transplantation in our hospital between March 1989 and July 2001. Seventy-three patients (47 males and 26 females) received CsA and short-term methotrexate for GVHD prophylaxis. CsA 1.5 mg/kg was administered as a 3-h infusion twice daily from day 1 until the patient recovered from the toxic gastrointestinal complication. Methotrexate was given at a dose of 15 mg/m(2) on day 1 and 10 mg/m(2) on days 3, 6 and 11. Grades II-IV acute GVHD occurred in 18 patients (24.7%). Multivariate Cox regression analysis revealed that higher C(5) (the whole-blood CsA concentration at 5 h after the start of infusion) before the onset of acute GVHD reduced the onset of grades II-IV acute GVHD with a hazard ratio of 0.994 (95% confidence interval 0.989-0.999) for every increase of 1 ng/ml. Our data indicate that inadequate exposures of CsA can be a vital risk for developing acute GVHD. From our results, we consider that precise monitoring of CsA concentrations and adjustment of CsA dose using the concentration may be effective to prevent the onset of severe acute GVHD. To confirm this finding, further prospective study will be needed. PMID- 17724442 TI - Selective recruitment of stem cell donors with rare human leukocyte antigen phenotypes. AB - Many patients in need of a hematopoietic stem cell transplant do not find a fully matching donor although more than 11,000,000 potential donors are registered worldwide. Therefore, it is relevant to recruit donors who add diversity to the donor pool. We present the 'Roots' approach that includes the selection of already registered donors with rare HLA phenotypes and the recruitment of relatives of these donors. Two projects (Roots A and B) with different donor selection criteria were carried out. HLA phenotype frequency distributions of new donors differ significantly from the respective control groups: 2.7% of Roots A donors versus 1.1% of the control group have an HLA-AB phenotype that is unique in the DKMS file (P=0.001). Additionally, 39.5% of Roots B donors but only 18.3% of the control group have a unique HLA-ABDR phenotype (P<0.001). Similar results are found when phenotypes that are at most available 10 times in the DKMS donor file are analyzed. The results show that the Roots approach is generally suited to increasing the ratio of donors with rare HLA phenotypes in a donor file. Additional costs of Roots donor recruitment seem justified through the ratio of recruited donors with rare HLA phenotypes. PMID- 17724441 TI - Association of squamous cell carcinoma of the oral cavity in allogeneic hematopoietic stem cell transplant recipients. PMID- 17724443 TI - Recovery, viability and clinical toxicity of thawed and washed haematopoietic progenitor cells: analysis of 952 autologous peripheral blood stem cell transplantations. AB - Cryopreservation and thawing of haematopoietic stem cells are associated with cell loss and infusion-related toxicities. We analysed viability, total nucleated cell (TNC) and CD34+ cell recovery, and infusion-related toxicities of 952 thawed and washed products. Mean TNC and CD34+ viable cells recoveries were 55.9+/-18.6 and 98.0+/-36.5%, respectively. Mean cell viability was 68.25+/-18.9%. TNC recovery was correlated with viability but independent of the initial nucleated cell concentration. No difference in TNC recovery or viability was observed according to underlying diseases, except for myeloma, for which these variables were significantly lower (P<0.05). CD34+ cell recovery was not correlated with viability or CD34+ initial count and was similar for all diseases. Cryostorage duration was not associated with cell loss. Immediate adverse events occurred in 169 patients (19%) and were moderate (grade I or II) for the majority of patients. Clinical toxicity was associated with a higher infused cell number and the presence of clumps in infused bags. The washing procedure of cell products lead to a low rate of adverse events, but patients transplanted with high cell numbers or bags in which clumps were identified are predisposed to such complications. PMID- 17724444 TI - Evaluation of intervention strategy based on CMV-specific immune responses after allogeneic SCT. AB - Late occurring CMV disease is an important problem after allogeneic SCT and has been associated with poor CMV-specific immunity. We conducted a prospective study of 58 patients studied at 3-6 months after allo-SCT, to base the antiviral therapy on monitoring of CMV-specific immunity. Reactivation of CMV was measured by quantitative PCR, and intracellular IFN-gamma production was analysed by FACS and enzyme-linked immunospot. Antiviral therapy was deferred in patients with documented CMV-specific immunity without symptoms of CMV disease or severe GVHD. Nineteen episodes of CMV reactivation were assessable. The strategy was correctly applied in 16/19 episodes. Therapy was deferred in 5/19 (none of these patients developed CMV disease) and was given according to the strategy in 11/19 episodes. Two patients received antiviral therapy despite having T cell-specific immunity. There was a tendency that patients with late CMV reactivation had weak CD8 T cell immunity at 3 months (P=0.06). The donors' serostatus influenced the strength of both CD4 and CD8 immunity at 3 months after SCT (P<0.01). There was no effect as regards the type of conditioning, donor type, stem cell source or acute GVHD. Monitoring the immunity of SCT patients may allow more targeted use of antiviral therapy. PMID- 17724445 TI - Six cases of leprosy associated with allogeneic hematopoietic SCT. AB - We report here the first six cases of leprosy associated with HLA-identical allogeneic SCT in different phases and with different findings and outcomes. Skin and peripheral nerves may be sites of leprosy associated with SCT, stressing the importance of differential diagnosis between leprosy and GVHD or drug reactions. Clinical manifestations of leprosy before or after transplantation did not influence the outcome of SCT in our cases. PMID- 17724446 TI - Long-term outcomes in children with high-risk neuroblastoma treated with autologous stem cell transplantation. AB - We retrospectively analysed the outcomes of children transplanted for high-risk neuroblastoma (NB) at a single institution predominantly transplanted with total body irradiation and chemotherapy. The aims of this study were to determine the prognostic impact of clinical and biological features and to document long-term health outcomes. Forty patients were transplanted with a single unpurged autograft. Fourteen patients died from disease progression and two from late complications of treatment. Twenty-three patients are alive at a median of 4.6 years from diagnosis. Kaplan-Meier estimates of overall survival at 2, 5 and 10 years are 76+/-7.0, 60.2+/-8.4 and 54.7+/-9.3% following transplant. Response to induction therapy was significantly associated with survival (P<0.01). Long-term complications included growth (100%) and pubertal failure (83%), hearing impairment (73%), orthopaedic complications (63%), renal impairment (47%) and thyroid abnormalities (36%). Intrinsic and acquired resistance to chemotherapy remains the major obstacle to improving outcomes in high-risk NB. Although patients with chemo-sensitive disease are less likely to experience a relapse, substantial therapy-related toxicities result in poor long-term health outcomes for survivors. PMID- 17724447 TI - Reduced-intensity conditioning for allogeneic hematopoietic stem cell transplantation with fludarabine and melphalan is associated with durable disease control in myelodysplastic syndrome. AB - We retrospectively evaluated the outcome of reduced-intensity conditioning (RIC) followed by allogeneic hematopoietic stem cell transplantation (HCT) in 43 patients with myelodysplastic syndrome (MDS) or AML arising from MDS. All patients received fludarabine plus melphalan followed by an allogeneic HCT from an HLA-identical sibling (SIB: n=19) or unrelated donor (MUD: n=24). Median age was 58 years (range: 30-71). Diagnoses at transplantation were RA (n=8), RARS (n=1), RAEB (n=13), RAEB-T (n=6), or AML arising from MDS (n=15). Of 28 patients with MDS, two patients had low, 10 had intermediate-1, nine had intermediate-2 and seven had high-risk MDS by IPSS criteria. All patients initially engrafted with the median neutrophil recovery of 15 days (range: 9-27). The 2-year overall survival, disease-free survival, relapse and transplant-related mortality were 53.5% (CI 45.2-61.1), 51.2% (CI 43.3-58.5), 16.3% (CI 7.9-30.7) and 35.2% (26.4 45.7), respectively. Grade II-IV acute graft-versus-host disease occurred in 27 (63%) patients. There was no significant survival difference between SIB and MUD HCT, but the relapse rate was higher among SIB donor recipients when compared to MUD (38.5 versus 7%, P=0.02). RIC with fludarabine plus melphalan was associated with durable disease control and acceptable toxicity in this high-risk cohort. PMID- 17724448 TI - Pathobiology of transforming growth factor beta in cancer, fibrosis and immunologic disease, and therapeutic considerations. AB - Transforming growth factor beta (TGF-beta) is a highly pleiotropic cytokine that plays an important role in wound healing, angiogenesis, immunoregulation and cancer. The cells of the immune system produce the TGF-beta1 isoform, which exerts powerful anti-inflammatory functions, and is a master regulator of the immune response. However, this is context dependent, because TGF-beta can contribute to the differentiation of both regulatory (suppressive) T cells (Tr cells) and inflammatory Th17 cells. While TGF-beta might be underproduced in some autoimmune diseases, it is overproduced in many pathological conditions. This includes pulmonary fibrosis, glomerulosclerosis, renal interstitial fibrosis, cirrhosis, Crohn's disease, cardiomyopathy, scleroderma and chronic graft-vs-host disease. In neoplastic disease, TGF-beta suppresses the progression of early lesions, but later this effect is lost and cancer cells produce TGF-beta, which then promotes metastasis. This cytokine also contributes to the formation of the tumor stroma, angiogenesis and immunosuppression. In view of this, several approaches are being studied to inhibit TGF-beta activity, including neutralizing antibodies, soluble receptors, receptor kinase antagonist drugs, antisense reagents and a number of less specific drugs such as angiotensin II antagonists and tranilast. It might be assumed that TGF-beta blockade would result in severe inflammatory disease, but this has not been the case, presumably because the neutralization is only partial. In contrast, the systemic administration of TGF beta for therapeutic purposes is limited by toxicity and safety concerns, but local administration appears feasible, especially to promote wound healing. Immunotherapy or vaccination stimulating TGF-beta production and/or Tr differentiation might be applied to the treatment of autoimmune diseases. The benefits of new therapies targeting TGF-beta are under intense investigation. PMID- 17724449 TI - Matrix Gla protein is involved in elastic fiber calcification in the dermis of pseudoxanthoma elasticum patients. AB - Mature MGP (Matrix gamma-carboxyglutamic acid protein) is known to inhibit soft connective tissues calcification. We investigated its possible involvement in pseudoxanthoma elasticum (PXE), a genetic disorder whose clinical manifestations are due to mineralization of elastic fibers. PXE patients have lower serum concentration of total MGP compared to controls (P<0.001). Antibodies specific for the noncarboxylated (Glu-MGP) and for the gamma-carboxylated (Gla-MGP) forms of MGP were assayed on ultrathin sections of dermis from controls and PXE patients. Normal elastic fibers in controls and patients were slightly positive for both forms of MGP, whereas Gla-MGP was more abundant within control's than within patient's elastic fibers (P<0.001). In patients' calcified elastic fibers, Glu-MGP intensively colocalized with mineral precipitates, whereas Gla-MGP precisely localized at the mineralization front. Data suggest that MGP is present within elastic fibers and is associated with calcification of dermal elastic fibers in PXE. To investigate whether local cells produce MGP, dermal fibroblasts were cultured in vitro and MGP was assayed at mRNA and protein levels. In spite of very similar MGP mRNA expression, cells from PXE patients produced 30% less of Gla-MGP compared to controls. Data were confirmed by immunocytochemistry on ultrathin sections. Normal fibroblasts in vitro were positive for both forms of MGP. PXE fibroblasts were positive for Glu-MGP and only barely positive for Gla MGP (P<0.001). In conclusion, MGP is involved in elastic fiber calcification in PXE. The lower ratio of Gla-MGP over Glu-MGP in pathological fibroblasts compared to controls suggests these cells may play an important role in the ectopic calcification in PXE. PMID- 17724450 TI - Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells. AB - In vitro reprogramming of somatic cells into a pluripotent embryonic stem cell like state has been achieved through retroviral transduction of murine fibroblasts with Oct4, Sox2, c-myc and Klf4. In these experiments, the rare 'induced pluripotent stem' (iPS) cells were isolated by stringent selection for activation of a neomycin-resistance gene inserted into the endogenous Oct4 (also known as Pou5f1) or Nanog loci. Direct isolation of pluripotent cells from cultured somatic cells is of potential therapeutic interest, but translation to human systems would be hindered by the requirement for transgenic donors in the present iPS isolation protocol. Here we demonstrate that reprogrammed pluripotent cells can be isolated from genetically unmodified somatic donor cells solely based upon morphological criteria. PMID- 17724452 TI - Hemodialysis-associated amyloidosis with cervical spinal cord compression and incomplete tetraplegia: a case report. AB - STUDY DESIGN: Case report. OBJECTIVES: To report a rare case of hemodialysis associated amyloidosis of cervical spinal canal with incomplete tetraplegia in long-term hemodialysis patient. SETTINGS: Traumatology Clinic, Zagreb; Spinal Unit, Varazdinske Toplice, Croatia. METHODS: Forty-seven-year-old male patient at long-term hemodialysis treatment developed progressive limbs weakness, graded as C4 ASIA C. Cervical computed tomography myelography showed extreme narrowing of the spinal canal. Decompressive laminectomy with bilateral foraminotomies was performed and histological examination revealed amyloidal deposition. RESULTS: Rehabilitation program started immediately after surgery with physical and occupational therapy, along with psychological support aiming at restoring full activities of daily living. Three months after surgery, the patient returned to his community, neurologically improved to ASIA E. Hemodialysis program was regularly maintained perioperatively and during the rehabilitation. CONCLUSION: Vertebral involvement with neurological deterioration in hemodialysis-associated amyloidosis patients prompts for early diagnosis, surgical and rehabilitation management, in this instance with good outcome.Spinal PMID- 17724451 TI - Antibodies neutralizing Nogo-A increase pan-cadherin expression and motor recovery following spinal cord injury in rats. AB - STUDY DESIGN: A rat model of spinal cord injury was used to test the hypothesis that Nogo-A monoclonal antibody (NEP1-40) promotes morphologic and functional recoveries of injured spinal cord. OBJECTIVE: Nogo-A is a myelin-associated neurite outgrowth inhibitory protein, which blocks elongation nerve fibers and limits neuronal regeneration after central nervous system injury. METHODS: Forty four rats were utilized and allocated into control (vehicle) and NEP1-40-treated groups. In all animals, the spinal cord was hemi-transected at Th-10 and phosphate-buffered saline solution was immediately applied on the injured area in the control group. NEP1-40 solution was immediately applied on the hemi transected area in the treatment group. Each group was subdivided into three subgroups according to the postsurgical day of killing (3, 8 and 21 days). The spinal cords were removed for analysis. RESULTS: Motor scores in the NEP1-40 treated groups were significantly higher than those in the vehicle groups both at 8 and 21 days post injury. Immunohistochemical staining for pan-cadherin, a marker of neuronal cell adhesion and axonal sprouting, revealed a significant increase in staining in the NEP1-40 treatment group at 8 and 21 days post injury. Transmission electron microscopical evaluation revealed degeneration of the myelin and loss of cytoarchitectural organization in the axons of controls. Better preservation and normal histologic features were observed in the NEP1-40 treated groups. CONCLUSION: We have demonstrated improved preservation of injured axons and significant pan-cadherin expression after NEP1-40 treatment after the spinal cord injury. Inhibition of Nogo-A may improve the capacity for neuronal regeneration after spinal cord injury. PMID- 17724453 TI - Neonatal latex allergy. PMID- 17724454 TI - Unexpected source of latex sensitization in a neonatal intensive care unit. AB - We report a term infant with gastroschisis who presented with a systemic allergic reaction at a specific time of each day coinciding with infusion from a new preparation of total parenteral nutrition and intravenous lipid emulsion. The source of latex was traced to the rubber stopper of the lipid emulsion. We present this case to highlight the possibility of allergy from this unexpected source in a neonate. PMID- 17724455 TI - Currarino syndrome as an etiology of a neonatal Escherichia coli meningitis. AB - We report the case of a 29-day-old baby girl in whom Escherichia coli meningitis led to the diagnosis of Currarino syndrome (CS) (OMIM 176450), an autosomal dominant genetic disorder associated with sacral agenesis, anorectal malformation, presacral masses and spinal cord malformations. Her condition improved with antibiotics and early surgical treatment. A familial study identified other genetically related individuals with similar symptoms. PMID- 17724456 TI - Passive cooling to initiate hypothermia for transported encephalopathic newborns. AB - Two newborns at high risk for severe encephalopathy were passively cooled by discontinuing the supplied heat from a radiant warmer. Cooling was attempted in both babies (successfully in one) before the arrival of the neonatal transport team. Both infants had core temperatures of approximately 34 degrees C on arrival at the NICU. Passive cooling may be an effective method to initiate cooling very early in the course of encephalopathy. PMID- 17724457 TI - sIL-6R: more than an agonist? AB - On target cells, interleukin-6 (IL-6) interacts with its receptor complex consisting of the membrane-bound IL-6 receptor (IL-6R) and the signal transducing protein gp130. IL-6R can exist as a soluble protein (sIL-6R), which binds the ligand IL-6. This soluble complex can bind to gp130 on cells that lack the membrane-bound IL-6R and initiate signaling. This process is named transsignaling. The significance of transsignaling via sIL-6R is underlined by different publications and exceeds very probably the significance of the membrane bound IL-6R. It is the general assumption that sIL-6R acts as an agonist in combination with IL-6 resulting in an enhancement of the IL-6 effects. In this article, we suppose 'non-agonistic' properties. There are several publications that give reasons to speculate that sIL-6R (a) has IL-6-antagonistic effects, (b) has orphan properties and (c) interacts with yet unknown binding partners different from IL-6. Knowledge about additional properties of sIL-6R will enlarge the biologic understanding of this molecule and might give an explanation for the sometimes contrasting effects of the cytokine IL-6. PMID- 17724460 TI - Regulation of mitotic exit by the RNF8 ubiquitin ligase. AB - RNF8 is a ubiquitin ligase with a FHA domain near its N terminus, and a RING finger domain at its C terminus, through which it recruits several ubiquitin conjugating enzymes. In metazoans, only the mitotic checkpoint regulator CHFR shares this domain architecture. Here we show that RNF8 is a nuclear protein that follows a cell-cycle-dependent turnover, reaching its highest levels in mitosis, followed by a strong decline in late mitotic stages. Overexpression of RNF8 caused a delay in cytokinesis and the frequent appearance of aberrant mitotic figures. These effects were dependent on the ubiquitin ligase activity of RNF8, since they were significantly attenuated when a RING-finger mutant, inactive as an E3, was overexpressed. Depletion of RNF8 also caused a delay in the exit from the mitotic arrest induced by nocodazole, associated with a reduced turnover of the APC/C substrate cyclin B1. These observations suggest that RNF8 regulates the rate of exit from mitosis and cytokinesis. PMID- 17724458 TI - Carbohydrate residues downstream of the terminal Galalpha(1,3)Gal epitope modulate the specificity of xenoreactive antibodies. AB - Carbohydrates are involved in many immunological responses including the rejection of incompatible blood, tissues and organs. Carbohydrate antigens with Galalpha(1,3)Gal epitopes are recognized by natural antibodies in humans and pose a major barrier for pig-to-human xenotransplantation. Genetically modified pigs have been established that have no functional alpha1,3-galactosyltransferase (alpha1,3GT), which transfers alphaGal to N-acetyllactosamine (LacNAc) type oligosaccharides. However, a low level of Galalpha(1,3)Gal is still expressed in alpha1,3GT knockout animals in the form of a lipid, isoglobotrihexosylceramide (iGb3), which is produced by iGb3 synthase on lactose (Lac) type core structures. Here, we define the reactivity of a series of monoclonal antibodies (mAb) generated in alpha1,3GT-/- mice immunized with rabbit red blood cells (RbRBC), as a rich source of lipid-linked antigens. Interestingly, one mAb (15.101) binds weakly to synthetic and cell surface-expressed Galalpha(1,3)Gal on LacNAc, but strongly to versions of the antigen on Lac cores, including iGb3. Three dimensional models suggest that the terminal alpha-linked Gal binds tightly into the antibody-binding cavity. Furthermore, antibody interactions were predicted with the second and third monosaccharide units. Collectively, our findings suggest that although the terminal carbohydrate residues confer most of the binding affinity, the fine specificity is determined by subsequent residues in the oligosaccharide. PMID- 17724461 TI - AZGP1 mRNA levels in normal human lung tissue correlate with lung cancer disease status. AB - Evidence in animal models has suggested an association between susceptibility to lung tumorigenesis and gene-expression profiles in normal lung. Here, we compared RNA pools from normal lung tissue of lung adenocarcinoma patients (cases) or non lung cancer patients (controls) by hybridization of whole-human genome expression arrays. Principal component analysis identified a gene-expression signature of 85 genes that distinguishes cases from controls as well as smokers from nonsmokers. Elevated mRNA levels of one of these genes, AZGP1, were significantly associated with disease status. These results support the hypothesis that differences in the gene-expression levels of the normal tissue may be predictive of genetic predisposition to lung cancer in humans. PMID- 17724462 TI - The transcriptional repressor NIPP1 is an essential player in EZH2-mediated gene silencing. AB - EZH2 is a Polycomb group (PcG) protein that promotes the late-stage development of cancer by silencing a specific set of genes, at least in part through trimethylation of associated histone H3 on Lys 27 (H3K27). Nuclear inhibitor of protein phosphatase-1 (NIPP1) is a ubiquitously expressed transcriptional repressor that has binding sites for the EZH2 interactor EED. Here, we examine the contribution of NIPP1 to EZH2-mediated gene silencing. Studies on NIPP1 deficient cells disclose a widespread and essential role of NIPP1 in the trimethylation of H3K27 by EZH2, not only in the onset of this trimethylation during embryonic development, but also in the maintenance of this repressive mark in proliferating cells. Consistent with this notion, EZH2 and NIPP1 silence a common set of genes, as revealed by gene-expression profiling, and NIPP1 is associated with established Polycomb target genes and with genomic regions that are enriched in Polycomb targets. Furthermore, most NIPP1 target genes are trimethylated on H3K27 and the knockdown of either NIPP1 or EZH2 is often associated with a loss of this modification. Our data reveal that NIPP1 is required for the global trimethylation of H3K27 and is implicated in gene silencing by EZH2. PMID- 17724463 TI - Activation of the mitochondrial death pathway is commonly mediated by a preferential engagement of Bak. AB - Among the members of the Bcl-2 family, the multidomain proteins Bax and Bak are crucial for the activation of mitochondria. However, it is still unclear whether they act in a unique and distinct manner or whether they exhibit redundant functions. To systematically investigate their activation on a single-cell level, we established MCF-7 cell lines stably expressing GFP-fusion variants of these proteins. We found that MCF-7/GFP-Bak cells showed an increased sensitivity to apoptosis induction by staurosporine, actinomycin D, TRAIL and overexpression of Puma compared to GFP-Bax-expressing cells. Independently of the death stimulus used, oligomerization of endogenous and exogenous Bak was mostly detected prior to an activation of Bax, whereas cells displaying oligomerized Bax in the absence of Bak clusters were not observed. In addition, activation of Bax but not Bak was attenuated by a caspase inhibitor. Consistent with this, caspase-3-deficient MCF 7 cells displayed a significantly reduced activation of endogenous Bax than caspase-3-proficient MCF-7 cells. Thus, our data strongly suggest that diverse apoptotic stimuli preferentially engage the Bak pathway, whereas the triggering of Bax occurs, at least partially, downstream of mitochondrial caspase activation, most likely constituting a positive feedback loop for the amplification of the death signal. PMID- 17724464 TI - Bfl-1/A1 functions, similar to Mcl-1, as a selective tBid and Bak antagonist. AB - The prosurvival Bcl-2-family member Bfl-1/A1 is a transcriptional target of nuclear factor-kappaB (NF-kappaB) that is overexpressed in many human tumors and is a means by which NF-kappaB inhibits apoptosis, but its mode of action is controversial. To better understand how Bfl-1 functions, we investigated its interaction with proapoptotic multidomain proteins Bax and Bak, and the BH3-only proteins Bid and tBid. We demonstrate that in living cells Bfl-1 selectively interacts with Bak and tBid, but not with Bax or Bid. Bfl-1/Bak interaction is functional as Bfl-1 suppressed staurosporine (STS)-induced apoptosis in wild-type and Bax-deficient cells, but not in Bak-/- cells. We also show that Bfl-1 blocks tumor necrosis factor-alpha (TNFalpha)-induced activation of Bax indirectly, via association with tBid. C-terminal deletion decreased Bfl-1's interaction with Bak and tBid and reduced its ability to suppress Bak- and tBid-mediated cell death. These data indicate that Bfl-1 utilizes different mechanisms to suppress apoptosis depending on the stimulus. Bfl-1 associates with tBid to prevent activation of proapoptotic Bax and Bak, and it also interacts directly with Bak to antagonize Bak-mediated cell death, similar to Mcl-1. Thus, part of the protective function of NF-kappaB is to induce Mcl-1-like activity by upregulating Bfl-1. PMID- 17724465 TI - Deregulated Wnt/beta-catenin program in high-risk neuroblastomas without MYCN amplification. AB - Neuroblastoma (NB) is a frequently lethal tumor of childhood. MYCN amplification accounts for the aggressive phenotype in a subset while the majority have no consistently identified molecular aberration but frequently express MYC at high levels. We hypothesized that activated Wnt/beta-catenin (CTNNB1) signaling might account for this as MYC is a beta-catenin transcriptional target and multiple embryonal and neural crest malignancies have oncogenic alterations in this pathway. NB cell lines without MYCN amplification express higher levels of MYC and beta-catenin (with aberrant nuclear localization) than MYCN-amplified cell lines. Evidence for aberrant beta-catenin-TCF transcriptional activity was demonstrated using expression profiles from 73 primary NBs. Findings included increased WNT ligands (WNT1, WNT6, WNT7A, WNT10B), DVL1 and TCF7 expression in high-risk NBs without MYCN amplification, consistent with canonical beta-catenin signaling. More directly, Patterns of Gene Expression and Gene Set Enrichment Analyses demonstrated beta-catenin target genes (for example, MYC, PPARD, NRCAM, CD44, TCF7) as coordinately upregulated in high-risk NBs without MYCN amplification in comparison to high-risk MYCN-amplified or intermediate-risk NBs, supporting pathway activation in this subset. Thus, high-risk NBs without MYCN amplification may deregulate MYC and other oncogenic genes via altered beta catenin signaling providing a potential candidate pathway for therapeutic inhibition. PMID- 17724466 TI - Epigenetic silencing of CXCL12 increases the metastatic potential of mammary carcinoma cells. AB - Expression of the chemokine receptor CXCR4 has been linked with increased metastasis and decreased clinical prognosis in breast cancer. The current paradigm dictates that CXCR4 fosters carcinoma cell metastasis along a chemotactic gradient to organs expressing the ligand CXCL12. The present study asked if alterations in autocrine CXCR4 signaling via dysregulation of CXCL12 in mammary carcinoma cells modulated their metastatic potential. While CXCR4 was consistently detected, expression of CXCL12 characteristic of human mammary epithelium was silenced by promoter hypermethylation in breast cancer cell lines and primary mammary tumors. Stable re-expression of functional CXCL12 in ligand null cells increased orthotopic primary tumor growth in the mammary fat-pad model of tumorigenesis. Those data parallel increased carcinoma cell proliferation measured in vitro with little-to-no-impact on apoptosis. Moreover, re-expression of autocrine CXCL12 markedly reduced metastatic lung invasion assessed using in vivo bioluminescence imaging following tail vein injection. Consistent with those data, decreased metastasis reflected diminished intracellular calcium signaling and chemotactic migration in response to exogenous CXCL12 independent of changes in CXCR4 expression. Together these data suggest that an elevated migratory signaling response to ectopic CXCL12 contributes to the metastatic potential of CXCR4-expressing mammary carcinoma cells, subsequent to epigenetic silencing of autocrine CXCL12. PMID- 17724467 TI - Analysis of transactivation capability and conformation of p53 temperature dependent mutants and their reactivation by amifostine in yeast. AB - The p53 gene is often mutated during cancer development. Frequency and functional consequences of these mutations vary in different tumor types. We analysed conformation and temperature dependency of 23 partially inactivating temperature dependent (td) p53 mutants derived from various human tumors in yeast. We found considerable differences in transactivation capabilities and discriminative character of various p53 mutants. No correlations in transactivation rates and conformations of the td p53 proteins were detected. Amifostine-induced p53 reactivation occurred only in 13 of 23 td mutants, and this effect was temperature dependent and responsive element specific. The most of the p53 mutations (10/13) reactivated by amifostine were located in the part of the p53 gene coding for hydrophobic beta-sandwich structure of the DNA-binding domain. PMID- 17724468 TI - Protein kinase C alpha-CARMA3 signaling axis links Ras to NF-kappa B for lysophosphatidic acid-induced urokinase plasminogen activator expression in ovarian cancer cells. AB - We reported previously that a signaling pathway consisting of G(i)-Ras-NF-kappaB mediates lysophosphatidic acid (LPA)-induced urokinase plasminogen activator (uPA) upregulation in ovarian cancer cells. However, it is not clear what signaling components link Ras to nuclear factor (NF)-kappaB for this LPA-induced event. In the present study, we found that treatment of protein kinase C (PKC) inhibitors including conventional PKC (cPKC) inhibitor Go6976 abolished LPA induced uPA upregulation in ovarian cancer cell lines tested, indicating the importance of cPKC activity in this LPA-induced event. Indeed, LPA stimulation led to the activation of PKCalpha and Ras-PKCalpha interaction. Although constitutively active mutants of PKCalpha (a cPKC), PKCtheta (a novel PKC (nPKC)) and PKCzeta (an atypical PKC (aPKC)) were all able to activate NF-kappaB and upregulate uPA expression, only dominant-negative PKCalpha mutant attenuated LPA induced NF-kappaB activation and uPA upregulation. These results suggest that PKCalpha, rather than PKC isoforms in other PKC classes, participates in LPA induced NF-kappaB activation and uPA upregulation in ovarian cancer cells. To determine the signaling components downstream of PKCalpha mediating LPA-induced uPA upregulation, we showed that forced expression of dominant-negative CARMA3 or silencing CARMA3, Bcl10 and MALT1 with specific siRNAs diminished these LPA induced events. Furthermore, we demonstrated that PKCalpha/CARMA3 signaling axis is important in LPA-induced ovarian cancer cell in vitro invasion. PMID- 17724470 TI - Sustained TGF beta exposure suppresses Smad and non-Smad signalling in mammary epithelial cells, leading to EMT and inhibition of growth arrest and apoptosis. AB - To better understand the dual, tumour-suppressive and tumour-promoting function of transforming growth factor-beta (TGFbeta), we analysed mammary epithelial NMuMG cells in response to short and long-term TGFbeta exposure. NMuMG cells became proliferation-arrested and apoptotic after exposure to TGFbeta for 2-5 days, whereas surviving cells underwent epithelial-mesenchymal transition (EMT). After chronic TGFbeta exposure (2-3 weeks), however, NMuMG cells became resistant to proliferation arrest and apoptosis, showing sustained EMT instead (TD cells). EMT was fully reversed by a pharmacologic TGFbeta-receptor-I kinase inhibitor or withdrawal of TGFbeta for 6-12 days. Interestingly, both cell cycle arresting/proapoptotic (Smads, p38 kinase) and antiapoptotic, proliferation and EMT-promoting signalling pathways (PI3K-PKB/Akt, ERK) were co-suppressed to low, but significant levels. Except for PI3K-Akt, TGFbeta-dependent downregulation of these signalling pathways in transdifferentiated (TD) cells was fully reversed upon TGFbeta withdrawal, together with partial re-induction of proliferation arrest and apoptosis. Co-injection of non-tumorigenic NMuMG cells with tumour forming CHO cells oversecreting exogenous TGFbeta1 (CHO-TGFbeta1) allowed outgrowth of epithelioid cells in CHO-TGFbeta1 cell-induced tumours. These epithelial islands enhanced CHO-TGFbeta1 tumour cell proliferation, possibly due to chemokines (for example, JE/MCP-1) secreted by NMuMG/TD cells. We conclude that suppression of antiproliferative, proapoptotic TGFbeta signalling in TD cells may permit TGFbeta-dependent proliferation, survival and EMT-enhancing signalling pathways to act at low levels. Thus, TGFbeta may modulate its own signalling to facilitate switching from tumour suppression to tumour progression. PMID- 17724469 TI - Reduced expression of vacuole membrane protein 1 affects the invasion capacity of tumor cells. AB - Vacuole membrane protein 1 (Vmp1) is described as a cancer-relevant cell cycle modulator, but the function of this protein and its mode of action in tumor progression are still unknown. In this study, we show that the VMP1 mRNA level is significantly reduced in kidney cancer metastases as compared to primary tumors. Further, VMP1 expression is also decreased in the invasive breast cancer cell lines HCC1954 and MDA-MB-231 as compared to the non-invasive cell lines MCF-12A, T-47D and MCF-7. We show for the first time that Vmp1 is a plasma membrane protein and an essential component of initial cell-cell contacts and tight junction formation. It interacts with the tight junction protein Zonula Occludens 1 and colocalizes in spots between neighboring HEK293 cells. Downregulation of VMP1 by RNAi results in loss of cell adherence, and increases the invasion capacity of the non-invasive kidney cancer cell line Caki-2. In conclusion, our findings establish Vmp1 to be a novel cell-cell adhesion protein and that its expression level determines the invasion and metastatic potential of cancer cells. PMID- 17724471 TI - Germline BRCA2 mutations and the risk of esophageal squamous cell carcinoma. AB - The incidence of esophageal squamous cell carcinoma (ESCC) is very high among the Turkmen population of Iran. Family studies suggest a genetic component to the disease. Turkmen are ethnically homogenous and are well suited for genetic studies. A previous study from China suggested that BRCA2 might play a role in the etiology of ESCC. We screened for mutations in the coding region of the BRCA2 gene in the germline DNA of 197 Turkmen patients with ESCC. A nonsense variant, K3326X, was identified in 9 of 197 cases (4.6%) vs 2 of 254 controls (0.8%) (OR=6.0, 95% CI=1.3-28; P=0.01). This mutation leads to the loss of the C terminal domain of the BRCA2 protein, a part of the region of interaction with the FANCD2 protein. We observed nine other BRCA2 variants in single cases only, including two deletions, and seven missense mutations. Six of these were judged to be pathogenic. In total, a suspicious deleterious BRCA2 variant was identified in 15 of 197 ESCC cases (7.6%). PMID- 17724472 TI - Disruption of cyclin D1 nuclear export and proteolysis accelerates mammary carcinogenesis. AB - Cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and polyubiquitination by SCF(FBX4-alphaB crystallin). Inhibition of cyclin D1 proteolysis has been implicated as a causative factor leading to its overexpression in breast and esophageal carcinomas; however, the contribution of stable cyclin D1 to the genesis of such carcinomas has not been evaluated. We therefore generated transgenic mice wherein expression of either wild-type or a stable cyclin D1 allele (D1T286A) is regulated by MMTV-LTR. MMTV-D1T286A mice developed mammary adenocarcinomas at an increased rate relative to MMTV-D1 mice. Similar to human cancers that overexpress cyclin D1, D1T286A tumors were estrogen receptor-positive and exhibited estrogen-dependent growth. Collectively, these results suggest that temporal control of cyclin D1 subcellular localization and proteolysis is critical for maintenance of homeostasis within the mammary epithelium. PMID- 17724474 TI - The histone deacetylase inhibitor trichostatin A induces GADD45 gamma expression via Oct and NF-Y binding sites. AB - The GADD45gamma protein is a potential tumor suppressor whose expression is reduced in several tumors. However, very little is known about the regulation of its expression. We have determined that the most relevant region of its promoter lies between nucleotides -112 and -54, relative to the transcription start site. Putative Oct and NF-Y elements were found in this region and factors belonging to these families interacted with these elements in vitro and with the promoter in vivo. Mutation of these elements reduced the basal activity of the promoter, suggesting that both sites are essential for basal expression. These factors interact with chromatin modifying proteins and we found that histone deacetylase 1 or silencing mediator for retinoid and thyroid hormone receptor overexpression reduced the basal activity of the promoter. In contrast, forced expression of the histone acetylase protein PCAF or cell treatment with the HDAC inhibitor trichostatin A increased GADD45gamma mRNA levels and induced GADD45gamma promoter activity through its Oct and NF-Y elements. Moreover, ectopic expression of a dominant-negative version of NF-YA strongly inhibited trichostatin A-induced activation of the promoter. Our data strongly suggest that inhibition of deacetylase activity could potentially be used for treatment of tumors where GADD45gamma expression is reduced. PMID- 17724473 TI - P-TEFb inhibitors interfere with activation of p53 by DNA-damaging agents. AB - Tumor suppressor p53 is stabilized in response to gamma-irradiation or treatment with DNA-damaging agents, and as a result p53 transcriptionally activates its targets leading to cell-cycle arrest or apoptosis. P-TEFb (positive transcription elongation factor b) inhibitors such as flavopiridol or 4-amino-6-hydrazino-7-b-d ribofuranosyl-7H-pyrrolo[2,3-d]-pyrimidine-5-carboxamide (ARC) upregulate p53 protein levels, but inhibit the expression of its targets p21 and hdm2. DNA damaging agents, doxorubicin and cisplatin are being used in combination with P TEFb inhibitor flavopiridol in clinical trials for the treatment of some cancer patients. In this study, we found that P-TEFb inhibitors block the phosphorylation of p53 induced by doxorubicin. Furthermore, treatment of cells with P-TEFb inhibitors together with doxorubicin inhibits doxorubicin-induced binding of p53 to DNA and p53 transcriptional activity. These data suggest that P TEFb inhibitors may antagonize the activation of p53 by DNA-damaging agents in tumors with wild-type p53. PMID- 17724475 TI - The activity of hsp90 alpha promoter is regulated by NF-kappa B transcription factors. AB - Heat-shock proteins (HSP) 90 exert a relevant role in the survival and response to therapy of many neoplastic cell types. Here, we show that the promoter of hsp90alpha gene, that encodes the inducible form of HSP90, is regulated by nuclear factor-kappaB (NF-kappaB) activity. Indeed, we found that NF-kappaB factors bound to one of the two putative consensus sequences present in the hsp90alpha-flanking region; mutation of such motif hampered the phorbol-myristate 13-acetate-stimulated expression of a luciferase reporter gene under the control of the hsp90alpha promoter. Furthermore, the downmodulation of NF-kappaB (p65) levels by a specific small interfering (si) RNA resulted in reducing the levels of endogenous HSP90alpha protein. These findings disclose a previously unrecognized mechanism that contributes to connect NF-kappaB factors and HSPs in cell defence machinery. PMID- 17724477 TI - BRAF(E600) in benign and malignant human tumours. AB - Of the RAF family of protein kinases, BRAF is the only member to be frequently activated by mutation in cancer. A single amino acid substitution (V600E) accounts for the vast majority and results in constitutive activation of BRAF kinase function. Its expression is required to maintain the proliferative and oncogenic characteristics of BRAF(E600)-expressing human tumour cells. Although BRAF(E600) acts as an oncogene in the context of additional genetic lesions, in primary cells it appears to be associated rather with transient stimulation of proliferation. Eventually, BRAF(E600) signalling triggers cell cycle arrest with the hallmarks of cellular senescence, as is illustrated by several recent studies in cultured cells, animal models and benign human lesions. In this review, we will discuss recent advances in our understanding of the role of BRAF(E600) in benign and malignant human tumours and the implications for therapeutic intervention. PMID- 17724476 TI - Regulation of cyclin D1 expression by mTORC1 signaling requires eukaryotic initiation factor 4E-binding protein 1. AB - There is currently substantial interest in the regulation of cell function by mammalian target of rapamycin (mTOR), especially effects linked to the rapamycin sensitive mTOR complex 1 (mTORC1). Rapamycin induces G(1) arrest and blocks proliferation of many tumor cells, suggesting that the inhibition of mTORC1 signaling may be useful in cancer therapy. In MCF7 breast adenocarcinoma cells, rapamycin decreases levels of cyclin D1, without affecting cytoplasmic levels of its mRNA. In some cell-types, rapamycin does not affect cyclin D1 levels, whereas the starvation for leucine (which impairs mTORC1 signaling more profoundly than rapamycin) does. This pattern correlates with the behavior of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1, an mTORC1 target that regulates translation initiation). siRNA-mediated knock-down of 4E-BP1 abrogates the effect of rapamycin on cyclin D1 expression and increases the polysomal association of the cyclin D1 mRNA. Our data identify 4E-BP1 as a key regulator of cyclin D1 expression, indicate that this effect is not mediated through the changes in cytoplasmic levels of cyclin D1 mRNA and suggest that, in some cell types, interfering with the amino acid input to mTORC1, rather than using rapamycin, may inhibit proliferation. PMID- 17724479 TI - Off-label use of drug-eluting stents: assessing the risk. PMID- 17724480 TI - Do corticosteroids prevent atrial fibrillation after cardiac surgery? PMID- 17724478 TI - Proapoptotic compound ARC targets Akt and N-myc in neuroblastoma cells. AB - We have previously described the identification of a nucleoside analog transcriptional inhibitor ARC (4-amino-6-hydrazino-7-beta-D-ribofuranosyl-7H pyrrolo[2,3-d]-pyrimidine-5-carboxamide) that was able to induce apoptosis in cancer cell lines of different origin. Here, we report the characterization of ARC on a panel of neuroblastoma cell lines. We found that these cell lines were more than 10-fold sensitive to ARC than to the well-known nucleoside analog DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole), and that ARC-induced apoptosis proceeds through mitochondrial injury. Also, we observed that ARC mediated cell death was accompanied by caspase-3 cleavage and repression of antiapoptotic proteins such as Mcl-1 and survivin. Conversely, we found that overexpression of Mcl-1-protected neuroblastoma cell line NB-1691 from ARC induced apoptosis. Furthermore, we found that while ARC inhibited the phosphorylation of Akt Ser-473 in multiple cancer cell lines, forced expression of myristoylated Akt promoted resistance to ARC-induced apoptosis in neuroblastoma cells. In addition, we observed that ARC was able to downregulate the protein levels of N-myc, a commonly amplified oncogene in neuroblastomas, and Akt protected N-myc from ARC-induced downregulation. These data suggest that ARC may antagonize different antiapoptotic pathways and induce apoptosis in neuroblastoma cells via multiple mechanisms. Overall, ARC could represent an attractive candidate for anticancer drug development against neuroblastomas. PMID- 17724481 TI - Elderly patients should not be denied fibrinolytic therapy. PMID- 17724482 TI - Is orbital decompression a safe and effective treatment for Graves' orbitopathy? PMID- 17724484 TI - A multidisciplinary approach to the management of children with complex genital anomalies. PMID- 17724483 TI - Does the andropause exist? PMID- 17724485 TI - What is the role of EUS in screening for chronic pancreatitis? PMID- 17724486 TI - Is mycophenolate mofetil really necessary in renal transplantation? A review of the MYSS follow-up study. PMID- 17724488 TI - Flu-related neurological complications: incidence and risk factors in children. PMID- 17724487 TI - Diagnosis of distal renal tubular acidosis: use of furosemide plus fludrocortisone versus ammonium chloride. PMID- 17724489 TI - Should cranial MRI screening of preterm infants become routine? PMID- 17724490 TI - Metastatic eyelid disease associated with hepatocellular carcinoma. AB - CASE REPORT: The eyelid is an unusual site for metastasis. We report a case of hepatocellular carcinoma in which eyelid lesions were the presenting sign of metastatic disease. This 76-year-old female patient presented with a recent history of a chalazion of her right upper and lower eyelids. Biopsy of 1 lesion showed moderately differentiated metastatic hepatocellular carcinoma. She had been diagnosed with hepatocellular carcinoma 15 months previously and had no evidence of metastasis up to that point. COMMENT: Eyelid lesions are rarely the initial manifestation of metastatic disease. This report and literature review of metastatic eyelid disease underscore the importance of considering metastasis in the differential diagnosis of eyelid lesions. PMID- 17724491 TI - Ultrasound biomicroscopy of eyelid eccrine hidrocystoma. AB - CASE REPORT: A 58-year-old white female noted a lesion on her left lower eyelid, present for 3 months. Examination disclosed a dark-blue, subepithelial, smooth mass along the cilia near the punctum. The lesion did not transmit light and was thought to be a solid mass, such as a deep-blue nevus or melanoma versus a cystic mass with internal debris. Ultrasound biomicroscopy showed a fairly circumscribed echolucent mass measuring 3.2 x 3.5 mm suggestive of a cyst with numerous internal echo impedances. Following resection, histopathologic evaluation disclosed a cyst lined by a dual layer of eccrine sweat ductal epithelium, consistent with eccrine hidrocystoma. COMMENTS: Eyelid hidrocystomas can be pigmented and can be confused clinically with melanocytic tumors. Ultrasound biomicroscopy can provide helpful diagnostic information about the internal architecture of such lesions. PMID- 17724492 TI - Retinal tear and raised intraocular pressure following unintentional intraocular botulinum toxin type A injection. AB - CASE REPORT: A 67-year-old woman with a 30-year history of dysthyroid orbitopathy and diplopia had an inadvertent injection of botulinum toxin type A into the vitreous cavity. Full pupil mydriasis and an intraocular pressure (IOP) of 50 mm Hg in the right eye were noted after the injection. An attack of acute angle closure was initially suspected despite a patent peripheral iridotomy (PI). The episode resolved with topical and intravenous IOP-lowering agents. Postoperative retinal examination revealed a retinal tear, which was successfully treated with laser photocoagulation. Visual acuity returned to baseline within 2 weeks, and the results of further retinal examinations remained stable. COMMENTS: This case supports the animal studies and human case reports that have demonstrated no retinal toxicity after intraocular injections of botulinum toxin type A. Temporary mydriasis and elevated IOP that may occur after injection do not appear to be detrimental and can be treated with topical and intravenous IOP-lowering agents. Transiently elevated IOP after injection is most likely due to volume increase, though acute angle closure with occlusion of the PI might be considered. PMID- 17724493 TI - Dietary lutein, zeaxanthin, and fats and the progression of age-related macular degeneration. AB - BACKGROUND: To estimate the effect of dietary intake of lutein and zeaxanthin (L/Z) and fats on the progression of age-related macular degeneration (AMD). METHODS: Two hundred and fifty-four subjects identified with early age-related macular degeneration (AMD) were re-examined to determine 7-year AMD progression. Intakes of L/Z and fatty acids were estimated from food frequency questionnaires. Progression was defined by 3 different definitions, 2 quantitative and 1 qualitative, which varied in the stringency of the change required for the AMD to be deemed to have progressed. Covariates included age, smoking, AMD family history, source study, and follow-up duration. RESULTS: Energy-adjusted L/Z intake as a continuous variable was associated with AMD progression in the worse affected eye when defined by the most stringent criterion (odds ratio [OR] = 2.65, 95% confidence interval [CI] 1.13-6.22, p = 0.02). Similar associations were observed for the 2 other progression definitions (p = 0.18 and p = 0.13). Energy-adjusted omega-3 fatty acid intake modelled as a quintile median was associated with AMD progression only in the side-by-side assessment (OR = 2.56, 95% CI 1.11-5.91, p = 0.03), with borderline significance in the other 2 definitions (p = 0.05 and p = 0.08). No association of AMD progression was observed with the intake of either total fat or other subgroups: saturated, polyunsaturated, or monounsaturated fats; trans fatty acids; or omega-6 fatty acids. INTERPRETATION: The findings of the study are counterintuitive, suggesting that increased intakes of dietary L/Z and omega-3 fatty acids are associated with progression of AMD. These results may indicate that too much of a good thing might be harmful. It is possible that in this study participants adopted a more healthy diet, having been aware of their AMD status at the beginning of the study. This healthy diet was then reflected in the dietary questionnaire completed at the end of study. However, this explanation may not adequately explain why those whose AMD had progressed, on the basis of fundus signs and not symptoms such as visual acuity decline, adopted a healthier lifestyle more aggressively than those without progression. PMID- 17724494 TI - Weight effect of saline accumulation in surgical drapes. AB - BACKGROUND: Positive vitreal pressure during phacoemulsification is a known risk factor for posterior capsule rupture. Knowledge of modifiable causes of positive vitreal pressure is imperative to aid in its management intraoperatively. The aim of our study was to determine whether the weight from the accumulation of a large volume of saline in the surgical drapes could have an effect on intraocular pressure in patients. Such an effect could indicate a source of posterior vitreal pressure in patients undergoing prolonged phacoemulsification. METHODS: In 23 adult patients undergoing phacoemulsification at the Jones Eye Institute at the University of Arkansas for Medical Sciences, intraocular pressure readings were taken before and after the addition of 500 cc of saline to the surgical drapes and taken again after removal of the saline. RESULTS: Statistically significant differences in intraocular pressure were found between the baseline measurement, the measurement with saline, and the measurement after saline removal. No differences in the rise in intraocular pressure were found according to age, race, sex, or which eye was tested. INTERPRETATION: Accumulation of a large volume of saline in surgical drapes has a modest effect on intraocular pressure. This may indicate a contributing cause of posterior vitreal pressure during prolonged phacoemulsification. PMID- 17724495 TI - A live attenuated human rotavirus vaccine. AB - Rotavirus infections are the leading cause of severe gastroenteritis in young children worldwide. This review provides a summary of the development of a live oral rotavirus vaccine, Rotarix (GlaxoSmithKline, Rixensart, Belgium) developed from a single protective G1P[8] human strain. To attenuate the wild-type virus, the original isolate, 89-12, was passaged multiple times in tissue culture. Large safety and efficacy trials that have included more than 100,000 children around the world have shown the vaccine is safe and not associated with intussusception. The vaccine is highly immunogenic and protective against disease caused by all the most common circulating human serotypes. Efficacy against severe rotavirus gastroenteritis and hospitalization has ranged from 85-100%. Rotarix is available in the European Union, most countries in Latin America, Australia, and numerous other countries around the world. The vaccine is administered as two oral doses with at least four weeks between doses. The first dose may be administered from the age of 6 weeks, and both doses should be completed by 24 weeks of age. PMID- 17724496 TI - Telbivudine for the treatment of chronic hepatitis B. AB - The hepatitis B virus (HBV) has a complex natural history and causes a wide spectrum of disease. Choices of therapy depend on a number of factors predictive of treatment response, clinical circumstances and stage of disease, and the likelihood and consequences of resistance to treatment. Telbivudine (beta-L 2'deoxythymidine) is a thymidine analogue that belongs to a new class of beta-L configuration nucleoside analogues with specific activity against hepadnavirus. Phase III studies of telbivudine versus lamivudine in hepatitis B e antigen (HBeAg) and anti-HBe have been completed. In HBeAg-positive patients, HBV DNA was not detectable by polymerase chain reaction (PCR) assay in 56% of the HBeAg positive patients receiving telbivudine after two years of treatment. In HBeAg negative patients, at two years, HBV DNA was undetectable by PCR in 82% of HBeAg negative patients (versus 52% of lamivudine recipients). Patients who were PCR negative after 24 weeks were less likely to develop resistance. HBeAg seroconversion rates were also greatest in patients whose HBV DNA was undetectable at 24 weeks. These results are promising and could be used to devise a strategy to utilize combination therapy or to adjust therapy if an inadequate early viral response is observed. However, resistance is a potential shortcoming of the use of single agents for the treatment of HBV. PMID- 17724497 TI - Dalbavancin: a review. AB - Dalbavancin is a second-generation lipoglycopeptide bactericidal agent. Due to its once-weekly intravenous (i.v.) dosing and greater tissue penetration, dalbavancin may offer advantages in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) as compared to vancomycin, the gold standard in the treatment of MRSA. Dalbavancin binds to the terminal D-alanyl-D-alanine moiety of peptidoglycan precursors in bacterial cell walls. Such binding blocks enzymes involved in the final stages of peptidoglycan synthesis and cell wall formation. Dalbavancin exhibits an elimination half-life of approximately 200 hours, allowing it to be dosed weekly. The best-studied dosing schedule for dalbavancin involves the i.v. administration of 1 g of dalbavancin followed by 500 mg one week later. Phase III clinical trials comprising more than 1,500 patients evaluated once-weekly dalbavancin in Gram-positive skin and soft tissue infections (SSTIs). When compared to linezolid, cefazolin or vancomycin, dalbavancin met the primary endpoint of noninferiority at two weeks following therapy. The side-effect profile of dalbavancin is mild, with headache and pyrexia being the most common adverse effects. Dalbavancin is eliminated renally and hepatically, and does not need dose adjustments in patients with renal insufficiency. Once-weekly dosing with dalbavancin gives it another advantage when compared with vancomycin, and may alleviate the need for the continued presence of indwelling catheters in some patients with SSTIs and other infections requiring prolonged doses of antibiotics. While some in vitro evidence supports dalbavancin's effectiveness against vancomycin-resistant S. aureus, the preponderance of in vivo evidence does not demonstrate its effectiveness against vancomycin-resistant S. aureus. PMID- 17724498 TI - Exploiting the PTHrP signaling pathway to treat chronic lung disease. AB - Despite tremendous advances in intensive care in general and respiratory care in particular, chronic lung disease (CLD) still remains a major cause of morbidity and mortality both in the premature infant and adult. This is primarily due to a lack of understanding of the molecular mechanisms involved in both normal and abnormal lung development. Based on the cellular/molecular mechanisms involved in physiologic lung development, we have taken a basic biologic approach to elucidate the pathophysiology of CLD. Stretch regulated parathyroid hormone related protein (PTHrP) signaling between the alveolar type II (ATII) cell and the mesoderm coordinately upregulates the key genes for the homeostatic fibroblast phenotype, which in turn stimulates surfactant synthesis by ATII cells. Under the influence of conditions that predispose to CLD, normal PTHrP signaling is disrupted and interstitial fibroblasts transdifferentiate to myofibroblasts, the hallmark cell of CLD. We have exploited the understanding of these molecular processes to demonstrate the proof-of-principle that by stabilizing the alveolar PTHrP signaling pathway using exogenously administered agonists of peroxisome proliferator-activated receptor-gamma a key target of PTHrP signaling, we can prevent and/or rescue the molecular injuries caused by insults that lead to CLD. Based upon extensive work from our laboratory, we suggest a novel and innovative molecular approach to prevent and/or treat fibrotic conditions in general and CLD in particular. However, to avoid any subsequent unexpected adverse consequences, it is important to emphasize that before translating the suggested approach into human trials, further testing and refinement in animal models is needed. PMID- 17724499 TI - Beta-amyloidbased immunotherapy as a treatment of Alzheimers disease. AB - The pathology of Alzheimer's disease shows a significant correlation between beta amyloid peptide conformation and the clinical severity of dementia. For many years efforts have been focused on the development of inhibitors of beta-amyloid formation and its related neurotoxic effects. A new concept has been developed which shows that site-directed antibodies may modulate formation of beta-amyloid. The performance of anti-beta-amyloid antibodies in transgenic mice models of Alzheimer's disease showed that they are delivered to the central nervous system, preventing in vivo formation of beta-amyloid. Moreover, those antibodies dissolve beta-amyloid plaques and protect the mice from learning and age-related memory deficits. Experimental active immunization with beta-amyloid (1-42) in humans was stopped in phase II of their clinical trials. However, several new preparations, able to provide antibodies against beta-amyloid by either active or passive routes, have been formulated and have reached clinical testing. The data presented support the hypothesis that beta-amyloid peptide plays a central role in Alzheimer's disease, and antibodies which modulate beta-amyloid conformation may lead to immunotherapy of the disease. PMID- 17724515 TI - [Health and aging in the 20th century]. PMID- 17724517 TI - [Functionality and health: a typology of aging in Mexico]. AB - OBJECTIVE: To analyze present conditions of aging in Mexico within the scope of health status and risk factors. MATERIALS AND METHODS: Four types of aging are depicted: ideal, active, habitual and pathological. Indicators include chronic diseases, cognitive impairments, functional capacity, health self-assessment, consumption of alcohol and tobacco and physical activity. Data come from the survey of the population 50 years and older in the 2001 Mexican Health and Aging Study (MHAS). RESULTS: Findings corroborate the relations between aging and each one of the variables studied, but even more importantly, they indicate a typology that combines all variables in a single index. CONCLUSIONS: The typology that resulted from this study provides guidelines for delimiting the factors that lead to aging under good conditions and, therefore, suggests interventions and plans for good health and wellbeing, although it also indicates that pathological aging can occur at an early age. In addition, new research topics arose. PMID- 17724516 TI - [Mexican older adults with a wide socioeconomic perspective: health and aging]. AB - OBJECTIVES: Describe the Estudio Nacional de Salud y Envejecimiento en Mexico (ENASEM), also known by its name in English as the Mexican Health and Aging Study (MHAS). MATERIALS AND METHODS: This article summarizes the study design, its fieldwork protocol, survey contents, scope and analytical potential. It also presents descriptive results on selected topics. This is a prospective panel study on persons aged 50 or older in the year 2000. RESULTS: In the baseline survey, completed in 2001 with a national and urban-rural representation, about 15 200 interviews were completed. In the follow-up survey of the same persons in 2003, 90% of the attempted contacts resulted in successful interviews, and 546 interviews were completed about individuals who had died between the 2001 and 2003 visits. Descriptive results are presented on demographic characteristics, health, life style, institutional support, pensions, employment, family help, and two-year changes in health. CONCLUSIONS: There is evidence of large heterogeneity among older adults in Mexico, which is illustrated in a brief and precise way in the results presented. This study and its data bases have great analytical potential for exploring multiple dimensions in the health of older adults. PMID- 17724518 TI - [Functional dependence and chronic disease in older Mexicans]. AB - OBJECTIVE: The aim of this study is to determine the prevalence of functional dependence in older Mexicans and associated chronic conditions. MATERIAL AND METHODS: The study was conducted between June and December 2004 in the Geriatric Department of the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City. The data for the variables were obtained from the information in the National Study of Health and Aging in Mexico survey (ENASEM). The survey was based on the law for statistical and geographic information,Chapter V, Article 38. A total of 4,872 subjects from the national survey of aging and health in Mexico were asked about their need for help in basic activities of daily living (BADL) and instrumental activities of daily living (IADL). Presence of disease was obtained through self-reporting. RESULTS: Prevalence of functional dependence was 24 and 23% for BADL and IADL, respectively. Joint disease, cerebrovascular disease, cognitive impairment and depression were associated with dependency in BADL and IADL. CONCLUSION: The prevalence of functional dependence is high among Mexicans over 65 years old. This study shows the chronic conditions that are closely associated with functional dependence and provides a perspective in order to develop preventative measures. PMID- 17724520 TI - [Cognitive impairment and associated factors in older adults in Mexico]. AB - OBJECTIVE: To determine the prevalence of cognitive impairment in the elderly and its relation with sociodemographic and health factors in the Mexican population. MATERIAL AND METHODS: From the first wave data of the National Aging and Health Study, collected in 2001 in Mexico, subjects 65 years or older and who had completed a cognitive assessment were selected. Subjects were classified according to two groups: with and without cognitive impairment, based on the cutoff point corresponding to the 10th percentile of the total cognitive assessment score, adjusted for age and educational level. All subjects with cognitive impairment that also had difficulty with one of the activities of daily living were classified as a third group: with cognitive impairment and functional dependency. Prevalence rates were calculated, and an association with demographic and health variables was established through regression analysis. RESULTS: Seven percent of the population had cognitive impairment while 3.3% had both conditions. The probability of cognitive impairment was not significantly associated with any demographic or health variables. Cognitive impairment and functional dependency indicated an association with gender, age, marital status, diabetes, stroke, heart disease and depression. CONCLUSIONS: The high prevalence of cognitive impairment and its relation with chronic disease frequently observed in the Mexican elderly suggest the need to increase early identification of both conditions in the population. PMID- 17724519 TI - [Cognitive impairment and alcohol and cigarette consumption in Mexican adults older than 65 years]. AB - OBJECTIVE: To determine the prevalence of the consumption of alcohol and cigarette smoking and their association with cognitive impairment among older Mexican adults. MATERIAL AND METHODS: A total of 4,872 people over 65 years of age included in the sample of the National Mexican Health and Aging Study carried out in 2001 were questioned about their consumption of alcohol and cigarette smoking. For the classification of those subjects with cognitive impairment, the total scale of the different cognitive domains was used. The chi-square, Mann Whitney U test, and logistical regression were used in order to find associations. RESULTS: The prevalence of alcoholism according to CAGE was 2.8% and the prevalence of the consumption of cigarette smoking was 14%. Factors associated with the consumption of alcohol were:age 65-69 (p <0.001), men (RR 3.17, p <0.001), and high level of education (p <0.001). The association between the consumption of alcohol and cognitive impairment (chi2=6.59, p <0.01) was statistically significant. CONCLUSIONS: The prevalence of consumption of alcohol and cigarette smoking in older Mexican adults are similar to that reported in other countries; the consumption of alcohol and its association with cognitive impairment was significant. PMID- 17724521 TI - Prevalence of self-reported overweight-obesity and its association with socioeconomic and health factors among older Mexican adults. AB - OBJECTIVE: To investigate the prevalence of obesity and its association with socioeconomic factors and comorbidities in a population-based study. MATERIAL AND METHODS: Data were examined from 4,605 persons ages 60 and older that participated in the 2001 Mexican Health and Aging Study, conducted in rural and urban communities in Mexico. The prevalence of obesity (according to self reported weight and height) was obtained, stratified by age, and logistic regression was used to study cross-sectional associations between obesity and socioeconomic factors. RESULTS: Of the population studied, 20.9% were classified as obese and the prevalence diminishes with age. Overall, women were more likely than men to be obese. Lower educational level was associated with lower risk of overweight. In both men and women, obesity was more common between subjects with hypertension (OR 1.38 and 1.71, respectively) and long-distance walk limitation (OR 2.08 and 2.21, respectively). CONCLUSION: In older Mexican adults, hypertension and long-distance walk limitation were independent associated factors for higher prevalence of obesity. PMID- 17724522 TI - [Pain in the elderly: prevalence and associated factors]. AB - OBJECTIVE: To determine the prevalence and the factors associated with pain in the Mexican elderly. MATERIAL AND METHODS: Persons ages 50 years or older answered the question: "Do you often suffer physical pain?" Prevalences were obtained, after which multivariate analyses were conducted for the entire sample and for each age group to determine the associated factors. RESULTS: Pain prevalence was 41.5%, more frequent in women (48.3% vs. 33.6%) and increased with age. There was a lower prevalence for persons with more education. Pain was directly associated with the report of arthritis, lung disease, falls, hypertension, depression, stroke, cancer history and problems with activities of daily living and instrumental activities of daily living. CONCLUSIONS: Pain is a common problem among elderly and is associated with some comorbidities. PMID- 17724523 TI - [Childhood health and social factors associated to elderly morbidity]. AB - OBJECTIVE: The aim was to determinate if health status of the elderly in Mexico at the beginning of the 21st. Century is associated to earlier social and health conditions during child-hood, including sex differences. MATERIAL AND METHODS: The research was conducted using survey data from the Mexican Health and Aging Study (MHAS) 2001. RESULTS: Linear regression models point out that life styles during childhood and adulthood are not independent, both influencing morbidity in elderly years. CONCLUSION: Parents' education and household characteristics through childhood represent main protection factors; however, this finding cannot be generalized. PMID- 17724524 TI - Health care utilization among older Mexicans: health and socioeconomic inequalities. AB - OBJECTIVE: To examine the determinants of the utilization of health care services among the population of older adults in Mexico. Three types of health care services are analyzed: preventive care, visits to the doctor, and hospitalizations. MATERIAL AND METHODS: Data was used from the 2001 Mexican Health and Aging Study (MHAS/ENASEM) and estimates were made using multivariate probit regression methods. RESULTS: Socioeconomic factors, health conditions reported by the individuals, and the availability of health insurance are significant determinants of the differential use of services by older adults. CONCLUSION: Specific health conditions are important determinants of use of the various types of health care services. For all three types, however, the availability of health insurance is an enabling factor of health care use. Older age is associated with greater propensity to use health care services but its effect is small when controlling for health conditions. PMID- 17724525 TI - [Gender and poverty: health determinants in old age]. PMID- 17724526 TI - Open letter in favor of the creation of asthma programs in Brazil. PMID- 17724527 TI - Asthma and gastroesophageal reflux disease. PMID- 17724528 TI - Another parameter for identifying obstructive respiratory disorder--FEV1/FEV6 in focus. PMID- 17724529 TI - Evaluation of pantoprazol treatment response of patients with asthma and gastroesophageal reflux: a randomized prospective double-blind placebo-controlled study. AB - OBJECTIVES: To determine the effect that the treatment of GERD has on the clinical management, as well as the respiratory function, of patients with asthma and to evaluate the clinical characteristics of this group of patients. METHODS: Patients with asthma and concomitant GERD, documented using 24 h pH-metry, were evaluated by means of quality of life questionnaires, as well as questionnaires related to respiratory and digestive symptoms. In addition, esophageal manometry, spirometry and the determination of peak expiratory flow were also performed prior to and after the study. Forty-nine individuals who were diagnosed with GERD by means of 24 h esophageal pH-metry were selected and participated in a clinical randomized double-blind placebo-controlled study, involving the administration of 40 mg/day of pantoprazol for 12 consecutive weeks. RESULTS: Forty-four individuals completed the study (n = 22 per group). There was significant improvement in the scores for respiratory symptoms and quality of life only in the group that received pantoprazol (p = 0.01 and p = 0.001, respectively). No respiratory function parameters changed in either group. CONCLUSIONS: In this study, the effective treatment of GERD improved patient quality of life, and the symptoms of asthma significantly decreased in the group that received the medication. There were no changes in pulmonary function parameters. PMID- 17724531 TI - Mediastinal lymph node distribution, size and number: definitions based on an anatomical study. AB - OBJECTIVE: To create a reference map of mediastinal lymph nodes through the analysis of their size, number and distribution in various lymph node stations. METHOD: A total of 50 cadavers, 38 males and 12 females, were studied. Of those 50, 39 were Caucasian. The mean age was 59.9 +/= 14.1 years, the mean height was 173.1 +/= 7.6 cm, and the mean weight was 71.0 +/= 12.0 kg. A bilateral mediastinal dissection was performed in order to resect and isolate all lymph nodes. The area, as well as the major and minor transverse diameters, of each lymph node was determined by radiographic imaging analysis. RESULTS: In a sample of 485 chains, 1742 lymph nodes were dissected (2.58 +/= 1.89 lymph nodes/station), revealing a mean number of 21.2 +/= 8.5 lymph nodes on the right and 13.6 +/= 6.3 on the left. The lymph node stations 1, 2R, 4R, 5, and 7 were present in more than 90% of the sample. Only the 4R and 7 lymph node stations were always present. The lymph node stations 2L, 3p, and 8 were present in 32, 36, and 54% of the sample, respectively. Mediastinal lymph nodes were present in greater numbers in the 2R, 4R and 7 lymph node stations. In addition, these stations presented the largest mediastinal lymph nodes. CONCLUSION: Composing a reference map for lymph node sizes was feasible. No alterations were observed in the distribution, number, or size of lymph nodes in the age brackets studied, regardless of gender, race, weight, or height. PMID- 17724532 TI - Comparative study of the resistance of manual and mechanical sutures in the bronchial stump of dogs submitted to left pneumonectomy. AB - OBJECTIVE: To compare the resistance of manual suture with that of mechanical suture immediately after the suture of the left bronchial stump of dogs submitted to pneumonectomy. METHODS: A total of 15 mixed-breed dogs of both genders, each weighing between 8 and 23 kg, were randomly divided into 2 groups. In group I (n = 7), the bronchial stump was sutured manually (the Sweet method) and, in group II (n = 8), it was stapled. Immediately after the closure of the bronchial stump, the intratracheal pressure was progressively increased in a controlled manner. RESULTS: The mean rupture pressure of the bronchial stump suture line was 33.71 mmHg in group I and 89.87 mmHg in group II (p < 0.01). CONCLUSION: These data allowed us to conclude that mechanical suture of the bronchial stump, submitted to pressure immediately after closure, is more resistant than is manual suture in dogs submitted to pneumonectomy. PMID- 17724533 TI - Determination of the efficacy of FEV6 as a surrogate for FVC in the diagnostic screening for chronic obstructive pulmonary disease through the comparison of FEV1/FVC and FEV1/FEV6 ratios. AB - OBJECTIVE: To determine the efficacy of using forced expiratory volume in six seconds (FEV6) as a surrogate for forced vital capacity (FVC) in the diagnostic screening for chronic obstructive pulmonary disease (COPD) by comparing FEV1/FVC ratios with FEV1/FEV6 ratios. METHODS: In November of 2003, on World COPD Day, we conducted a campaign of diagnostic screening for COPD. The participants completed the clinical questionnaire of the Global Initiative for Obstructive Lung Disease, and those who responded affirmatively to at least three questions underwent spirometry. RESULTS: A total of 134 individuals responded to three questions affirmatively and underwent spirometry. Of those, 59 were excluded: 45 for being non-smokers and 14 due to the fact that their tests did not meet the American Thoracic Society criteria for satisfactory spirometry. The number of tests in which the FEV1/FEV6 ratio was below 70% was similar to that found for the FEV1/FVC ratio. The sensitivity of FEV1/FEV6 in diagnosing airway obstruction (defined as FEV1/FVC below 70%) was 92%, and its specificity was 99%. The positive predictive value was 100%, and the negative predictive value was 98%. The Kendall correlation test revealed r = 0.99 (p < 0.0001). The t-test for paired samples revealed a negative correlation: t = -5.93 (p < 0.0001). CONCLUSION: The FEV1/FEV6 proved efficient for use in the diagnostic screening for COPD. There is a strong correlation between FEV1/FVC and FEV1/FEV6. PMID- 17724530 TI - Accuracy of the stair climbing test using maximal oxygen uptake as the gold standard. AB - OBJECTIVE: To determine the accuracy of the variables related to the fixed-height stair climbing test (SCT) using maximal oxygen uptake (VO2 max) as the gold standard. METHODS: The SCT was performed on a staircase consisting of 6 flights (72 steps; 12.16 m total height), with verbal encouragement, in 51 patients. Stair-climbing 'time' was measured, and the variables 'work' and 'power' also being calculated. The VO2 max was measured using ergospirometry according to the Balke protocol. We calculated the Pearson linear correlation (r), as well as the values of p, between the SCT variables and VO2 max. To determine accuracy, the VO2 max cut-off point was set at 25 mL/kg/min, and individuals were classified as normal or altered. The cut-off points for the SCT variables were determined using the receiver operating characteristic curve. The Kappa statistic (k) was used in order to assess concordance. RESULTS: The following values were obtained for the variable 'time': cut-off point = 40 s; x= 41 +/= 15.5 s; r = "0.707; p < 0.005; specificity = 89%; sensibility = 83%; accuracy = 86%; and k = 0.724. For 'power', the values obtained were as follows: cut-off point = 200 w; x= 222.3 +/= 95.2 w; r = 0.515; p < 0.005; specificity = 67%; sensibility = 75%; accuracy = 71%; and k = 0.414. Since the correlation between 'work' and VO2 max was not significant, that variable was discarded. CONCLUSION: Of the SCT variables tested, using VO2 max as the gold standard, the variable 'time' was the most accurate. PMID- 17724534 TI - Effect of theophylline associated with short-acting or long-acting inhaled beta2 agonists in patients with stable chronic obstructive pulmonary disease: a systematic review. AB - OBJECTIVES: To determine whether, in stable patients with chronic obstructive pulmonary disease, administration of theophylline in combination with short acting or long-acting inhaled beta2-agonists is more efficacious than is a placebo or each of these drugs used in isolation. METHODS: A systematic review and meta-analysis were carried out. All randomized and double-blind clinical trials found in the literature were selected. RESULTS: A total of eight studies were included. In comparing the effect of theophylline combined with beta2 agonists to that of a placebo, we found a statistically significant improvement in mean FEV1 (0.27 L; 95% CI: 0.11 to 0.43) and mean dyspnea (-0.78; 95% CI: 1.26 to -0.29). None of the meta-analyses performed detected any difference between the results obtained using theophylline combined with beta2-agonists and those obtained using beta2-agonists alone. When the administration of theophylline combined with beta2-agonists was compared to that of theophylline alone, there was a statistically significant improvement in mean dyspnea (-0.19; 95% CI: -0.34 to 0.04). CONCLUSION: In patients with stable chronic obstructive pulmonary disease, theophylline combined with beta2 agonists is more efficacious than is a placebo in terms of improving FEV1 and dyspnea. In addition, theophylline combined with beta2 agonists is more efficacious than is theophylline in improving dyspnea. Furthermore, administration of theophylline combined with beta2 agonists is no more efficacious, for any of the variables studied, than is the use of beta2-agonists in isolation. PMID- 17724535 TI - Influence of the oxygen delivery system on the quality of life of patients with chronic hypoxemia. AB - OBJECTIVE: To evaluate the health-related quality of life of patients with chronic obstructive pulmonary disease receiving long-term oxygen therapy (LTOT) at home through oxygen cylinders and compare these results with those obtained six months after the transition from oxygen cylinders to oxygen concentrators. METHODS: A total of 45 patients were evaluated. Of those, 24 had chronic hypoxemia and 21 presented no evidence of hypoxemia. The patients with chronic hypoxemia had been regularly receiving LTOT for at least the last six months and were evaluated at baseline, while using cylinders, and six months after the transition from cylinders to concentrators. The non-hypoxemic patients were evaluated at the same time points as were the hypoxemic patients. In order to evaluate quality of life, a version of the Saint George's Respiratory Questionnaire (SGRQ), translated and validated for use in Brazil, was administered. RESULTS: At baseline, quality of life, as evaluated using the total score and the symptom and impact domain scores of the SGRQ, was more impaired in the hypoxemic patients than in the non-hypoxemic patients. After six months of using the concentrators, the hypoxemic patients presented a significant improvement in the quality of life, and, at that time, no difference was found between the patients with and without hypoxemia. CONCLUSION: Our findings show that quality of life is impaired in patients with chronic obstructive pulmonary disease and chronic hypoxemia, that their quality of life can be improved through regular use of LTOT, and that the oxygen delivery system has an influence on this improvement. PMID- 17724536 TI - Comparative analysis and reproducibility of the modified shuttle walk test in normal children and in children with cystic fibrosis. AB - OBJECTIVE: To analyze the shuttle walk test, and its respective retest, comparing children with cystic fibrosis (CF) to normal children. METHODS: The children were divided into two groups: the CF group, composed of children in whom the diagnosis had been confirmed through sweat testing; and the control group, composed of normal children with no history of pulmonary diseases and no alterations in respiratory function. The children were submitted to at least two consecutive tests, 30 min apart. We evaluated distance walked, cardiac overload, peripheral oxygen saturation (SpO2) and subjective perception of exertion (dyspnea at rest scale and Borg dyspnea scale). RESULTS: A total of 28 children were evaluated. Ages ranged from 7 to 15 years (11.57 +/= 2.50 and 11.28 +/= 1.85 years for the CF and control groups, respectively). The Borg scale scores were significantly higher in the controls (p = 0.007). No differences were found regarding cardiac overload and SpO2. In relation to the intergroup retest, the controls presented significant improvements on the second test, both in the distance walked and in dyspnea at rest (p = 0.014 and p = 0.036, respectively). The CF group presented a significant improvement only in the dyspnea at rest score (p = 0.168 and p = 0.042, respectively). CONCLUSION: The cardiac overload imposed by the test did not differ between the groups. The greater fatigue at the beginning of the second test suggests that the 30 min rest between the tests was insufficient. PMID- 17724537 TI - Impact of the implementation of a therapeutic guideline on the treatment of nosocomial pneumonia acquired in the intensive care unit of a university hospital. AB - OBJECTIVE: To evaluate the impact that the implementation of therapeutic guidelines has on the empirical treatment of nosocomial pneumonia. METHODS: A clinical trial, using historical controls and involving current ICU patients who had acquired nosocomial pneumonia, was carried out from June of 2002 to June of 2003. All were treated according to therapeutic guidelines developed by the Commission for Nosocomial Infection Control of the institution (group with intervention). As controls, the medical charts of the patients who acquired nosocomial pneumonia between June of 2000 and June of 2001 (group without intervention) were analyzed. Mortality and mean treatment period, as well as the length of hospital and ICU stays, were determined for the patients who acquired nosocomial pneumonia. RESULTS: Mortality associated with pneumonia was lower in the group treated according to the therapeutic guidelines (26 vs. 53.6%; p = 0.00). As for overall mortality, there was no statistically significant difference between the two periods (51 vs. 57.9%; p = 0.37). There was also no difference in the type of microorganisms isolated, treatment period, length of hospital stay or length of ICU stay. CONCLUSION: The implementation of therapeutic guidelines for the treatment of nosocomial pneumonia acquired in the ICU can be efficacious in decreasing mortality rates. PMID- 17724538 TI - Evaluation of serum and pleural levels of the tumor markers CEA, CYFRA21-1 and CA 15-3 in patients with pleural effusion. AB - OBJECTIVE: To determine the levels of the tumor markers carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1) and carbohydrate antigen 15-3 (CA 15 3) in the blood and pleural fluid of patients with benign or malignant pleural effusion, evaluating the sensitivity of each marker in these fluids. METHODS: We prospectively evaluated 85 patients with pleural effusion. The study of the pleural fluid observed the criteria established in the literature. Levels of the markers were determined using electrochemiluminescence. The sensitivity was determined on the condition that the specificity was > or = 90%. RESULTS: Of the 85 cases, 36 (42.4%) were malignant, 30 (35.3%) were benign, and the results were inconclusive in 19 (22.3%). In the malignant cases, the CEA and CYFRA21-1 levels were higher in the pleural fluid than in the blood, which was not observed for CA 15-3. In the benign cases, the CYFRA21-1 levels were higher in the pleural fluid than in the blood, whereas the opposite was found for CEA and CA 15-3. There were significant differences between malignant and benign cases for all markers, in pleural fluid and blood. In the pleural fluid, the sensitivity of CEA, CYFRA21-1 and CA 15-3 was 69.4, 69.4 and 66.7%, respectively, and the combined sensitivity was 80.6%. In the blood, the sensitivity was 57.1%, 71.4% and 48.6% for CEA, CYFRA21-1 and CA 15-3, respectively, and the combined sensitivity was 77%. CONCLUSION: The results suggest that these markers might be useful in the differentiation between malignant and benign pleural effusion. PMID- 17724540 TI - Profile of patients with tuberculosis: evaluation of the Brazilian national tuberculosis control program in Bage, Brazil. AB - OBJECTIVE: To present epidemiological data on patients diagnosed with tuberculosis, as well as on associated factors, and to determine the efficacy of the National Tuberculosis Control Program in Bage, Brazil. METHODS: A retrospective study was carried out at the Pablo Barcellos Center, analyzing cases of tuberculosis reported from January 2001 to December 2004. Data were collected through the review of clinical charts and from the National Case Registry database. RESULTS: During this period, of the 4468 sputum smear microscopies performed, 131 were positive, with higher prevalence among males aged 26 to 35 years old. Prevalence was lower among those aged 65 and above. Over 50% of the patients were Caucasian, had only 1 to 3 years of schooling and worked in low-income jobs (mean salary, 265 Brazilian reals/month). There was no significant difference between smokers and former smokers/nonsmokers, and only one of the 131 cases was HIV positive. CONCLUSION: The number of sputum smear microscopies performed in Bage increased in the past four years. In 2003 and 2004, it exceeded the goal of the National Tuberculosis Control Program. However, the number of new cases decreased, demonstrating the efficacy of the active search for tuberculosis cases in the city. PMID- 17724539 TI - Descriptive study of the implementation and impact of the directly observed treatment, short-course strategy in the Sao Jose do Rio Preto municipal tuberculosis control program (1998-2003). AB - OBJECTIVE: To describe treatment outcomes (cure, noncompliance or death) after the implementation of the Directly Observed Treatment, Short-course (DOTS) strategy for tuberculosis control in the city of Sao Jose do Rio Preto, Brazil, between 1998 and 2003. METHODS: A descriptive study, based on secondary data (National Case Registry database, Tuberculosis Epidemiology database, and the 'Black Book' Registry), was conducted using a specific instrument. The data were analyzed using descriptive statistics. RESULTS: After the implementation of the DOTS strategy, there was a decrease in noncompliance and case detection rates as well as an increase in cure and death rates. The increase in the number of tuberculosis-related deaths might be attributable to three factors: the predominance of the disease in individuals over 50 years of age, tuberculosis/HIV co-infection, and the presence of accompanying diseases. CONCLUSION: The implementation of the DOTS strategy strengthened the decentralization of the tuberculosis control plans as well as the integration of the Basic Health Care Clinic teams with the Tuberculosis Control Program team. Political commitment of the administrator to tuberculosis control, in conjunction with the policy of benefits and incentives, is essential for the sustainability of the DOTS strategy. PMID- 17724541 TI - Transfusion-related acute lung injury. AB - Transfusion-related acute lung injury (TRALI) is a serious clinical syndrome associated with the transfusion of plasma-containing blood components. Recently, TRALI has come to be recognized as the leading cause of transfusion-related death in the United States and United Kingdom. This complication typically presents as shortness of breath, hypoxemia, hypotension, fever and noncardiogeneic pulmonary edema, all occurring during or within 6 h after transfusion. Although the mechanism of TRALI has not been fully elucidated, it has been associated with human leukocyte antigen antibodies (class I, class II or neutrophil alloantigens) and with biologically active mediators in stored cellular blood components. Most of the donors implicated in cases of TRALI are multiparous women. Rarely diagnosed, TRALI can be confused with other causes of acute respiratory failure. Greater knowledge regarding TRALI on the part of clinicians could be crucial in preventing and treating this severe complication of blood transfusion. PMID- 17724542 TI - Diabetes mellitus in patients with cystic fibrosis. AB - Cystic fibrosis-related diabetes (CFRD) is the principal extra-pulmonary complication of cystic fibrosis, occurring in 15-30% of adult cystic fibrosis patients. The number of cystic fibrosis patients who develop diabetes is increasing in parallel with increases in life expectancy. The aim of this study was to review the physiopathology, clinical presentation, diagnosis and treatment of CFRD. A bibliographic search of the Medline and Latin American and Caribbean Health Sciences Literature databases was made. Articles were selected from among those published in the last twenty years. Insulin deficiency, caused by reduced beta-cell mass, is the main etiologic mechanism, although insulin resistance also plays a role. Presenting features of type 1 and type 2 diabetes, CFRD typically affects individuals of approximately 20 years of age. It can also be accompanied by fasting, non-fasting or intermittent hyperglycemia. Glucose intolerance is associated with worsening of nutritional status, increased morbidity, decreased survival and reduced pulmonary function. Microvascular complications are always present, although macrovascular complications are rarely seen. An oral glucose tolerance test is recommended annually for patients > or = 10 years of age and for any patients presenting unexplained weight loss or symptoms of diabetes. Patients hospitalized with severe diseases should also be screened. If fasting hyperglycemia persists for more than 48 h, insulin therapy is recommended. Insulin administration remains the treatment of choice for diabetes and fasting hyperglycemia. Calories should not be restricted, and patients with CFRD should be managed by a multidisciplinary team. PMID- 17724543 TI - Mediastinal lymph node amyloidosis in a patient with sarcoidosis. AB - A 27-year-old male patient presented with respiratory symptoms, bilateral enlargement of the cervical lymph nodes and enlarged liver. In the imaging studies, bilateral enlargement of the hilar nodes was observed, together with pulmonary infiltrate. The patient was submitted to lung and liver biopsies, which revealed noncaseating granulomas. The clinical, radiological and histopathological findings were consistent with sarcoidosis and lymph node amyloidosis. The combination of sarcoidosis and amyloidosis has rarely been reported. PMID- 17724544 TI - Castleman's disease or angiofollicular hyperplasia as a solitary pulmonary nodule: case report. AB - Castleman's disease is a rare disorder generally characterized by a mediastinal nodule, with a great variety of alternative presentations regarding age, clinical manifestations and evolution. This case report describes a 40-year-old female patient presenting with uncharacteristic chest pain for a few years. A chest X ray revealed a hypotransparency on the right side. Computed tomography and pulmonary arteriography did not elucidate the diagnosis, which was made through surgical resection and anatomopathological examination of the nodule, which presented characteristics of angiofollicular hyperplasia, or Castleman's disease. This article emphasizes the importance of adding this disease to the list of morbidities in the differential diagnosis of pulmonary solitary nodules. PMID- 17724545 TI - Pulmonary lymphangiomatosis: a report of two cases. AB - Lymphangiomatosis, a rare diseases of controversial origin, occurs in individuals of any age, regardless of gender, but is predominantly seen in younger individuals. It often presents with thoracic involvement, although, the bones, spleen and liver can also be affected. Histologically, the pulmonary involvement includes proliferation, complex anastomoses and secondary dilatation of the lymphatic vessels. Clinically, the presentation is variable. Although radiographic findings can be suggestive of the disease, the final diagnosis is made histologically. We report two cases of lymphangiomatosis, both in females: one was oligosymptomatic and is being treated for the disease; the other had a more progressive form, was diagnosed quite late and ultimately died of the disease. PMID- 17724546 TI - Pulmonary metastases in men: primary tumor in an unusual location. AB - We report a case of breast cancer identified in a 72-year-old male as an accidental finding during the course of the investigation of a primary tumor and the search for pulmonary metastases. We address aspects related to the epidemiology, diagnosis, treatment and prognosis of this condition in males. PMID- 17724548 TI - Multi-disciplinary rehabilitation after hip fracture is associated with improved outcome: A systematic review. AB - BACKGROUND: While hip fractures are an important cause of disability, dependency and death in older adults, the benefit of multi-disciplinary rehabilitation for people who have sustained hip fracture has not been demonstrated. METHODS: Systematic review of randomized controlled trials which compare co-ordinated multi-disciplinary rehabilitation with usual orthopaedic care in older people who had sustained a hip fracture. Outcome measures included: mortality, return home, "poor outcome", total length of hospital stay, readmissions and level of function. RESULTS: We identified 11 trials including 2177 patients. Patients who received multi-disciplinary rehabilitation were at a lower risk (Risk Ratio 0.84, 95% CI 0.73-0.96) of a "poor outcome" - that is dying or admission to a nursing home at discharge from the programme, and showed a trend towards higher levels of return home (Risk Ratio 1.07, 95% CI 1.00-1.15). Pooled data for mortality did not demonstrate any difference between multi-disciplinary rehabilitation and usual orthopaedic care. CONCLUSION: This is the first review of randomized trials to demonstrate a benefit from multi-disciplinary rehabilitation; a 16% reduction in the pooled outcome combining death or admission to a nursing home. This result supports the routine provision of organized care for patients following hip fracture, as is current practice for patients after stroke. PMID- 17724549 TI - Actual vs best practice for families post-stroke according to three rehabilitation disciplines. AB - OBJECTIVE: To investigate occupational therapists', physiotherapists' and speech language pathologists' family-related rehabilitation practice post-stroke and its association with clinician and environmental variables. METHODS: A Canadian cross sectional telephone survey was conducted on 1755 clinicians. Three case studies describing typical patients after stroke receiving acute care, in-patient rehabilitation, or community rehabilitation, and including specific descriptors regarding family stress and concern, were used to elicit information on patient management. RESULTS: One-third of the sample identified a family-related problem and offered a related intervention, but only 12/1755 clinicians indicated that they would typically use a standardized assessment of family functioning. Working in the community out-patient setting was associated (OR 9.16), whereas working in a rehabilitation in-patient setting was negatively associated (OR 0.58) with being a problem identifier, the reference group being acute care. Being a PT (OR 0.53) or an SLP (OR 0.49) vs an OT was negatively associated with being a problem identifier, whereas being older (OR 1.02 ) or working in Ontario (OR 1.58) was associated with being a problem identifier. To work in a community out-patient setting (OR 2.43), being older clinicians (OR 1.02) or not perceiving their work environment being supportive of an on-going professional learning (OR 1.72) was associated with being an intervention user,whereas being a PT (OR 0.50) was negatively associated with being a user. CONCLUSION: For these 3 disciplines, the prevalence of a family-related focus is low post-stroke. Given the increasing evidence regarding the effectiveness of family-related interventions on stroke outcomes, it is imperative that best practice is implemented. PMID- 17724550 TI - Changes in proprioceptive systems activity during recovery from post-stroke hemiparesis. AB - OBJECTIVE: To investigate the activity of proprioceptive systems during early recovery of motor function after ischaemic stroke in a prospective, longitudinal, functional imaging study. METHODS: Ten patients with unilateral infarction of the posterior internal capsule were investigated using oxygen-15-water positron emission tomography during passive extension of the index finger. Patients were assessed initially after stroke (mean 4.7 days) and again after rehabilitation. Changes in brain activation patterns were analysed. RESULTS: All patients showed significant improvement in motor function of the paretic limb. During passive finger movement of the non-paretic index finger, significant increases in cerebral blood flow were observed in the somatosensory areas I and II (SI and SII) of the non-infarcted hemisphere. Additionally, significant activation of ipsilateral SII in the infarcted hemisphere was observed. After rehabilitation, ipsilateral SII activation vanished and the normal activation pattern was restored. During passive movement of the paretic index finger only SI and SII of the infarcted hemisphere were activated. During rehabilitation, additional recruitment of SII in the non-infarcted hemisphere occurred. CONCLUSION: Recovery from internal capsule infarction is accompanied by substantial changes in activity of proprioceptive systems of the paretic and non-paretic limb. These changes may reflect an inter-hemispheric shift of attention to proprioceptive stimuli associated with recovery. PMID- 17724552 TI - Assessment of postural instability in patients with traumatic brain injury upon enrolment in a vocational adjustment programme. AB - OBJECTIVE: To assess postural instability in patients with traumatic brain injury upon enrolment to vocational adjustment. DESIGN: A cross-sectional study. PATIENTS AND METHODS: Sixty-eight patients at the time of admission to a vocational adjustment programme and 52 healthy age-matched controls were evaluated. Complaints of dizziness, or balance impairment and data from a clinical examination were recorded. Postural characteristics during quiet upright standing were assessed using a static posturographic platform. RESULTS: Twenty six patients complained of dizziness or instability and 36 had evidence of neurological impairment. Centre of pressure displacement and area were significantly increased in the traumatic brain injury group as a whole, compared with controls, even among 23 patients who had no complaint or clinical abnormality. CONCLUSION: In spite of a high variability in time since injury, significant posturographic abnormalities were found in patients with traumatic brain injury, including those who had no complaints or evidence of neurological impairment. Posturography may help in understanding how a traumatic brain injury impairs the human balance, and may provide helpful information for patients participating in vocational adjustment programmes, especially when jobs require a long standing posture or balance. PMID- 17724551 TI - Ultrasonographic measurement of shoulder subluxation in patients with post-stroke hemiplegia. AB - OBJECTIVE: To evaluate the ultrasonographic measurement of shoulder subluxation in patients with post-stroke hemiplegia. DESIGN: Prospective, single blind study. PATIENTS: A total of 41 patients with post-stroke hemiplegia were included (24 men and 17 women, mean age 56 years (standard deviation 11), age range 34-78 years). METHODS: Clinical evaluation of the affected shoulder was assessed using the Motricity Index scores and the Modified Ashworth Scale. Two ultrasonographic measurements were taken to check intra-rater reliability. The shoulder subluxation ratio was determined as the ratio of the radiographic vertical and horizontal distance, and the ultrasonographic lateral and anterior distances in the affected shoulder divided by that in the unaffected shoulder. RESULTS: Intraclass correlation coefficients of the repeated ultrasonographic lateral/anterior distance measurements in the unaffected and affected shoulders were 0.979/0.969 and 0.950/0.947, respectively. Ultrasonographic lateral/anterior distance ratios were negatively correlated with Motricity Index scores of the affected shoulder abduction (r = -0.490, p < 0.001/ r = -0.671, p < 0.001). Ultrasonographic anterior distance ratio was negatively correlated with Modified Ashworth Scale score of the affected shoulder (r = -0.374, p < 0.05). However, there was no correlation between radiographic distance ratios and clinical evaluation scores. CONCLUSION: We strongly recommend ultrasonography as a diagnostic tool to measure the degree of shoulder subluxation in patients with post-stroke hemiplegia. PMID- 17724553 TI - Psychometric properties of an International Classification of Functioning, Disability and Health (ICF)-oriented, adaptive questionnaire for the assessment of mobility, self-care and domestic life. AB - OBJECTIVE: Development of an adaptive, International Classification of Functioning, Disability and Health (ICF)-oriented patient questionnaire on mobility and self-care based on an item response theory model (MOSES questionnaire). METHODS: Using item reconstruction rules, items were developed for the ICF chapters "mobility", "self-care" and "domestic life". The resulting instrument, together with other instruments (SF-36, Short Musculoskeletal Function Assessment Questionnaire (SMFA), MacNew, Functional Independence Measure (FIM), Barthel) was presented to 549 patients with musculoskeletal disease, 212 patients with cardiac disease and 258 neurological rehabilitation patients in rehabilitation clinics in Germany. RESULTS: The MOSES questionnaire includes 58 items on 12 scales and fulfills the requirements of the 1-parameter item response theory model (Rasch model). The results indicate good reliability and high construct validity and sensitivity to change of the instrument. In the construction and selection of items, ICF contents that include complex processes of evaluation, and which presuppose skills that are not acquired prior to the individual learning process, were omitted due to a lack of unidimensionality. CONCLUSION: The successful implementation of the concept of applying rules to ICF categories in formulating the items of a patient questionnaire showed that the goal of a theory-driven measurement of activities using the ICF is feasible. The results of the project also raise questions as to the homogeneity of the contents of some ICF categories. PMID- 17724554 TI - Application and validation of the barrow neurological institute screen for higher cerebral functions in a control population and in patient groups commonly seen in neurorehabilitation. AB - OBJECTIVE: To determine whether the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS) can differentiate brain-dysfunctional patients from controls. DESIGN: A case-control study. SUBJECTS: A total of 92 controls and 120 patients from a neuro-rehabilitation clinic with a diagnosis of: right and left hemisphere stroke, traumatic brain injury, Parkinson's disease or anoxic brain damage. METHODS: The BNIS has a maximum total score of 50 points, < 47 indicates cognitive dysfunction. Group comparisons and exploration of variables influencing the BNIS total score were made. RESULTS: A significant difference was found between the control group and the total patient group for the BNIS total score and for the subscales (p < 0.0005). Sensitivity was 88% and specificity 78%. Presence of disease and educational level had the greatest influence on the results of the BNIS. Patients with Parkinson's disease were shown to be the least cognitively affected and those with anoxic brain damage the most affected. CONCLUSION: The BNIS has potential value as a screening instrument for cognitive functions and is sufficiently sensitive to differentiate brain-dysfunctional patients from a control population. It appears to be applicable in a neurological rehabilitation setting, and can be used early in the process, giving a baseline cognitive functional level. PMID- 17724555 TI - Patients with neuromuscular diseases benefit from treatment in a warm climate. AB - OBJECTIVE: Several studies have shown positive effects of treatment of chronic diseases in a warm climate. The aim of this study was to evaluate the long-term effect of a 4-week rehabilitation programme in a warm climate for patients with neuromuscular diseases. DESIGN: A randomized controlled trial with a cross-over design. One period of intervention and one period of "life as usual". PATIENTS: A total of 60 persons with a neuromuscular diagnosis. METHODS: Long-term effects were defined as changes in physical and psychological functions persisting after 3 months. Several scales were used according to the World Health Organization's classification of functioning. RESULTS: A comparison of the changes in the 2 periods showed significantly better results for all primary outcome scales in favour of the intervention. Mean difference in changes in pain (VAS scale), 6-min walking test and "timed up and go" were 9.0 (SD 28.8) units, 52 (75) m and 1.0 (2.3) sec, p = 0, 03, < 0.01 and 0.01, respectively. Median difference in changes in "Fatigue Severity Scale" and "Life Satisfaction Scale" were 0.4 (-0.5, 1.7) and 0.0 (0.0, 1.0), p = < 0.01 and 0.01, respectively. CONCLUSION: This study shows positive long-term effects on different dimensions of health after a 4-week rehabilitation programme in a warm climate for patients with neuromuscular diseases. This effect might be due to the programme, the warm climate, or a combination of both. PMID- 17724556 TI - Life habits in myotonic dystrophy type 1. AB - OBJECTIVE: To describe and compare life habits between individuals with adult and mild phenotypes of myotonic dystrophy; identify life habit dimensions in which accomplishment is compromised; and describe satisfaction related to life habits. DESIGN: Cross-sectional study. SUBJECTS: A random sample of 200 subjects with myotonic dystrophy (42 mild phenotypes, 158 adult phenotypes). MEASUREMENT: The Assessment of Life Habits (LIFE-H), a questionnaire assessing self-perceived life habits (activities and participation as described in the International Classification of Functioning, Disability and Health (ICF)). RESULTS: Participants with the adult phenotype demonstrated significantly lower participation levels than those with the mild phenotype on 8 out of the 11 categories of the LIFE-H. Lower levels of accomplishment were reported in Mobility, Housing, Fitness, Nutrition, Personal Care, Employment, Recreation, and Community Life categories among the adult phenotype. The Recreation category was the most affected, with 4 out of 7 items revealing compromised accomplishment among 22-27% of individuals. The lowest satisfaction score was observed in the Employment and Recreation categories. In all categories, individuals with the adult phenotype displayed significantly lower satisfaction levels than those with the mild phenotype. CONCLUSION: This study helped to establish a clearer distinction between activities and participation levels of individuals with the mild phenotype and those with the adult phenotype and supported tailored rehabilitation and community services to improve accomplishment of life habits. PMID- 17724557 TI - Walking tasks encountered by urban-dwelling adults and persons with incomplete spinal cord injuries. AB - OBJECTIVE: Gait retraining should target the walking skills most needed for independence in the home and community. The main objective of this study was to document the walking tasks most commonly encountered in daily life by able-bodied adults. The study also compared participation in walking tasks between able bodied adults and persons with incomplete spinal cord injuries. PARTICIPANTS: Convenience sample of 50 able-bodied adults and 16 ambulatory, community-dwelling persons with incomplete spinal cord injuries. METHODS: A walking survey was developed, and its content validity and concurrent validity confirmed. Participants used the survey to document the frequency with which walking tasks were encountered during a full waking day. RESULTS: Frequently encountered tasks included walking on smooth and rough surfaces, opening/closing doors and carrying objects. Tasks encountered more than once per day by the majority of able-bodied participants included negotiating obstacles, walking on uneven and sloped surfaces, in crowded environments, narrow spaces, and on steps and stairs. Participants with spinal cord injuries encountered fewer tasks, including many of those frequently encountered by able-bodied participants. CONCLUSION: The findings identify the important walking tasks for ambulation in the home and community. These tasks should be included in therapy programs aiming to retrain functional walking. PMID- 17724558 TI - Effect of manual therapy and stretching on neck muscle strength and mobility in chronic neck pain. AB - OBJECTIVE: To study the effect of manual therapy and stretching on neck function in women with chronic neck pain. METHODS: A total of 125 women were randomized into 2 groups. Group 1 received manual therapy twice a week for 4 weeks followed by stretching exercises. Group 2 performed stretching 5 times a week for 4 weeks followed by manual therapy. Neck function was assessed by isometric neck strength and mobility measurements, and spontaneous neck pain during the past week and strain-evoked pain during the neck strength trials using a visual analogue scale. RESULTS: Both neck muscle strength (11-14%) and mobility (7-15%) improved similarly in both groups, with the exception of greater passive flexion-extension mobility (p = 0.019) in group 1 at week 4. Pain during the neck strength trials decreased from the baseline to week 4 by 26-35% and to week 12 by 39-61% similarly in both groups. Average neck pain during the past week decreased by 64% and 53% in groups 1 and 2, respectively, during the first 4 weeks, remaining rather stable thereafter. The decreases in neck pain during both the past week and strength trials showed association with the changes in neck strength results (r = 0.20-0.29). CONCLUSION: Both manual therapy and stretching were effective short-term treatments for reducing both spontaneous and strain-evoked pain in patients with chronic neck pain. It is possible that the decrease in pain reduced inhibition of the motor system and in part improved neck function. However, the changes in neck muscle strength were minor, showing that these treatments alone are not effective in improving muscle strength. PMID- 17724559 TI - Robot-mediated upper limb physiotherapy for patients with spastic hemiparesis: a preliminary study. AB - OBJECTIVE: To investigate the clinical usefulness of the REHAROB Therapeutic System, which provides passive robot-mediated physiotherapy for patients with spastic hemiparesis. DESIGN: Controlled, randomized, preliminary study. PATIENTS AND METHODS: Thirty patients with hemiparesis as a consequence of upper motor neurone lesion were divided randomly into 2 groups: robotic and control. Subjects from both groups received 30 minutes of Bobath therapy sessions on 20 consecutive work days. Members of the robotic group received an additional 30 minutes of robot-mediated therapy on the same days. The clinical status of each patient was assessed before the first session and at the end of the programme. The difference in the scores was statistically evaluated by t-test for dependent variables in case of parametric data and Friedman's test in case of non-parametric data. RESULTS: The majority of the parameters measured improved in both groups, but modified Ashworth score of shoulder adductors and elbow flexors showed a statistically significant change only in the robotic group. CONCLUSION: The results suggest that it could be useful to supplement traditional physiotherapy with this form of robot-mediated therapy. Clinical investigation of a higher number of patients is planned in the near future. PMID- 17724561 TI - Abstracts from the 32nd European Society of Neuroradiology (ESNR) Annual Meeting and 16th Advanced Course. September 20-23, 2007. Genoa, Italy. PMID- 17724568 TI - Introduction to special article on human rights. PMID- 17724567 TI - Quantifying sample biases of inland lake sampling programs in relation to lake surface area and land use/cover. AB - We quantified potential biases associated with lakes monitored using non probability based sampling by six state agencies in the USA (Michigan, Wisconsin, Iowa, Ohio, Maine, and New Hampshire). To identify biases, we compared state monitored lakes to a census population of lakes derived from the National Hydrography Dataset. We then estimated the probability of lakes being sampled using generalized linear mixed models. Our two research questions were: (1) are there systematic differences in lake area and land use/land cover (LULC) surrounding lakes monitored by state agencies when compared to the entire population of lakes? and (2) after controlling for the effects of lake size, does the probability of sampling vary depending on the surrounding LULC features? We examined the biases associated with surrounding LULC because of the established links between LULC and lake water quality. For all states, we found that larger lakes had a higher probability of being sampled compared to smaller lakes. Significant interactions between lake size and LULC prohibit us from drawing conclusions about the main effects of LULC; however, in general lakes that are most likely to be sampled have either high urban use, high agricultural use, high forest cover, or low wetland cover. Our analyses support the assertion that data derived from non-probability-based surveys must be used with caution when attempting to make generalizations to the entire population of interest, and that probability-based surveys are needed to ensure unbiased, accurate estimates of lake status and trends at regional to national scales. PMID- 17724569 TI - Gentamicin-induced anaphylaxis. AB - BACKGROUND: Gentamicin is a common cause of allergic contact dermatitis but immediate (type 1) hypersensitivity is unusual. AIMS AND METHODS: We report a case of anaphylaxis to gentamicin in a 69-year-old man who developed urticaria, hypotension and loss of consciousness within minutes of receiving intravenous gentamicin. RESULTS: The patient was successfully resuscitated and made a full recovery. Prick testing and patch testing to gentamicin was positive. CONCLUSIONS: Although allergic reactions to gentamicin are well recognised, there are few reported cases of anaphylaxis to gentamicin. PMID- 17724570 TI - Sestamibi scan-directed, minimally invasive video-assisted parathyroidectomy: an effective treatment for solitary parathyroid adenoma. AB - BACKGROUND: Solitary adenomas have been shown to be responsible for almost 90% of cases of primary hyperparathyroidism. AIM: The purpose of this study was to determine the utility of sestamibi scanning pre-operatively to guide minimally invasive video-assisted (MIVA) parathyroidectomy. METHODS: We reviewed 40 patients who underwent parathyroidectomy between 2003 and 2004. All patients underwent a pre-operative sestamibi scan. RESULTS: Thirty-three (82%) patients had a localized solitary adenoma on sestamibi scan. Of these patients 29 underwent attempted MIVA parathyroidectomy. MIVA parathyroidectomy was successful in 22 patients. When pre-operative sestamibi scanning was correlated with pathological diagnosis it was shown to have a sensitivity of 82% and positive predictive value of 94%. CONCLUSION: Pre-operative sestamibi scan localization of a parathyroid adenoma offers a 94% positive predictive value for adenoma location. This facilitates MIVA parathyroidectomy to be used effectively to treat primary hyperparathyroidism in the majority of patients. PMID- 17724571 TI - [Sinushistiocytosis with massive lymphadenopathy (Rosai-Dorfman disease)]. AB - Sinus histiocytosis with massive lymphadenopathy (SHML) is a rare, painless lymphoproliferative disorder of unknown origin with a usually benign course. About 40% of the patients show an extranodal involvement with skin being the most common site in 27% of these patients. We describe a patient with widespread disease involving the respiratory tract, kidneys and skin. Histopathology revealed the characteristic features of SHML with emperipolesis and immunohistochemical positivity of histiocytes for S100 and macrophage-associated antigens. PMID- 17724572 TI - Foraging scent marks of bumblebees: footprint cues rather than pheromone signals. AB - In their natural habitat foraging bumblebees refuse to land on and probe flowers that have been recently visited (and depleted) by themselves, conspecifics or other bees, which increases their overall rate of nectar intake. This avoidance is often based on recognition of scent marks deposited by previous visitors. While the term 'scent mark' implies active labelling, it is an open question whether the repellent chemicals are pheromones actively and specifically released during flower visits, or mere footprints deposited unspecifically wherever bees walk. To distinguish between the two possibilities, we presented worker bumblebees (Bombus terrestris) with three types of feeders in a laboratory experiment: unvisited control feeders, passive feeders with a corolla that the bee had walked over on its way from the nest (with unspecific footprints), and active feeders, which the bee had just visited and depleted, but which were immediately refilled with sugar-water (potentially with specific scent marks). Bumblebees rejected both active and passive feeders more frequently than unvisited controls. The rate of rejection of passive feeders was only slightly lower than that of active feeders, and this difference vanished completely when passive corollas were walked over repeatedly on the way from the nest. Thus, mere footprints were sufficient to emulate the repellent effect of an actual feeder visit. In confirmation, glass slides on which bumblebees had walked on near the nest entrance accumulated hydrocarbons (alkanes and alkenes, C23 to C31), which had previously been shown to elicit repellency in flower choice experiments. We conclude that repellent scent marks are mere footprints, which foraging bees avoid when they encounter them in a foraging context. PMID- 17724573 TI - Postmating changes in cuticular chemistry and visual appearance in Ectatomma tuberculatum queens (Formicidae: Ectatomminae). AB - In the ectatommine ant Ectatomma tuberculatum, the visual appearance of queens changes after mating and ovarian development in that their cuticle turns from shiny to matte. In this study, we have shown that this change seems to be caused by 15-fold accumulation of hydrocarbons, in particular heptacosane that covers the multiple grooves present on the cuticular surface creating a wax coat in mated fully fertile queens. Analyses of the scrapped wax revealed that it is composed largely of heptacosane. Peak-by-peak comparison of the cuticular hydrocarbon (CHC) composition of mated, virgin with developed ovaries and virgin with nondeveloped ovaries revealed significant differences between the queen groups. Although the total amount of the CHC of virgin queens with developed ovaries was not higher than virgin queens that did not have developed ovaries, the composition showed a shift toward the mated queen. While it is possible that the large accumulation of hydrocarbons may give extra physical and chemical protection to queens, we propose that the switch in the relative abundance of heptacosane and nonacosane and perhaps of other components is indicative of being a mating and fertility cue. This is the first report in social insects where external chemical changes are accompanied by changes in visual appearance. PMID- 17724574 TI - [Methylphenidate in adults with attention-deficit/hyperactivity disorder]. PMID- 17724575 TI - Fulminant type 1 diabetes in Korea: high prevalence among patients with adult onset type 1 diabetes. AB - AIMS/HYPOTHESIS: The aim of this study was to investigate the prevalence of fulminant type 1 diabetes and the clinical characteristics of the disease among newly diagnosed Korean patients. METHODS: Using data retrieved from the Seoul National University Hospital database, we identified all patients newly diagnosed with type 1 diabetes from 1 January 1999 to 31 July 2006. Information on clinical manifestations and laboratory data, including the presence of islet autoantibodies detected at diagnosis, were obtained by reviewing medical records. RESULTS: We identified 99 patients newly diagnosed with type 1 diabetes. Seven patients (7.1%) fulfilled the criteria for fulminant type 1 diabetes. Among the patients aged > or =18 years at onset, 30.4% had fulminant type 1 diabetes. Patients with this diabetes subtype tested negative for islet autoantibodies, had a higher age of onset (median 28 vs 10 years, p < 0.001) and a markedly shorter duration from onset of hyperglycaemic symptoms to first hospital visit (median 3 vs 30 days, p < 0.001) than patients with non-fulminant type 1 diabetes, and showed trends of increased serum aspartate aminotransferase and amylase levels and a decreased glucagon-stimulated serum C-peptide response. CONCLUSIONS/INTERPRETATION: In Korea, the prevalence of fulminant type 1 diabetes was 7.1% among all patients newly diagnosed with type 1 diabetes and 30.4% among patients with adult-onset diabetes. The clinical and metabolic characteristics of the patients with fulminant type 1 diabetes were similar to those reported in Japanese studies. PMID- 17724576 TI - Increased physical activity is a cornerstone in the prevention of type 2 diabetes in high-risk individuals. PMID- 17724577 TI - Increased skeletal muscle ceramide level in men at risk of developing type 2 diabetes. AB - AIMS/HYPOTHESIS: Intramyocellular lipids, including ceramide, a second messenger in the sphingomyelin signalling pathway, might contribute to the development of insulin resistance. The aim of our study was to assess parameters of the skeletal muscle sphingomyelin signalling pathway in men at risk of developing type 2 diabetes. METHODS: We studied 12 lean (BMI < 25 kg/m(2)) men without a family history of diabetes (control group), 12 lean male offspring of type 2 diabetic patients, and 21 men with overweight or obesity comprising 12 with NGT (obese NGT) and nine with IGT (obese-IGT). A euglycaemic-hyperinsulinaemic clamp and a biopsy of vastus lateralis muscle were performed. Ceramide, sphingomyelin, sphinganine and sphingosine levels and sphingomyelinase and ceramidase activities were measured in muscle. Muscle diacylglycerol and triacylglycerol levels were estimated in a subgroup of 27 men (comprising men from all the above groups). RESULTS: Compared with the control group, the lean offspring of diabetic patients and the men with overweight or obesity showed lower insulin sensitivity (all p < 0.005) and a greater muscle ceramide level (all p < 0.01). The obese-IGT group had lower insulin sensitivity (p = 0.0018) and higher muscle ceramide (p = 0.0022) than the obese-NGT group. There was lower muscle sphingosine level and alkaline ceramidase activity in offspring of diabetic patients (p = 0.038 and p = 0.031, respectively) and higher sphinganine level in the obese-NGT (p = 0.049) and obese-IGT (p = 0.002) groups than in the control group. Muscle sphingomyelin was lower (p = 0.0028) and neutral sphingomyelinase activity was higher (p = 0.00079) in the obese-IGT than in the obese-NGT group. Muscle ceramide was related to insulin sensitivity independently of other muscle lipid fractions. CONCLUSIONS/INTERPRETATIONS: Ceramide accumulates in muscle of men at risk of developing type 2 diabetes. PMID- 17724579 TI - Flow cell within an LED: a proposal for an optical absorption detector. AB - Droplets formed at the tip of a tube under the same conditions possess extreme uniformity of form, volume and weight. These properties of liquid drop formation have been known for a long time and consequently many applications for the drop have been found in instrumentation and chemical analysis methods. In the present paper, we report on the analytical use of a dynamic LED-based flow-through optical absorption detector with optical path length controlled by continuous dropping of a solution. This arrangement consists of a flow cell built within a high-intensity red LED (lambda(max) = 630 nm). The feasibility of the detector is demonstrated by colorimetric determination of methylene blue, and ammonium by Berthelot's reaction, in a flow-injection system. For ammonium, the reaction forms a blue dye (indophenol) with a maximum absorption at 630-650 nm. The detection limit, considered as 3 times the signal of the blank, is better than 125 microg l(-1). The small flow cell represents a good combination of optical path length, low volume and fast washout. This detector can be used advantageously in automated methods and can represent a solution to problems of optical detection involving gas bubbles and precipitation of particles in turbidimetric applications. PMID- 17724578 TI - Relative quantitation of proteins fractionated by the ProteomeLab PF 2D system using isobaric tags for relative and absolute quantitation (iTRAQ). AB - We describe an optimised protocol for application of isobaric tags for relative and absolute quantitation (iTRAQ) and tandem mass spectrometry to obtain relative quantitative data from peptides derived from tryptic digestions of proteins fractionated by using the 2D liquid-phase ProteomeLab PF 2D technique. This methodology is suitable for the quantitation of proteins from a pool of co eluting proteins which are often difficult to identify for the purpose of candidate protein selection for biologically relevant qualitative/quantitative changes under experimental conditions or in disease states. iTRAQ quantitation also facilitates the possibility of result to result comparison using other methodologies such as UV protein quantitation via the ProteomeLab PF 2D technique. The optimised protocol outlined here allows relative quantitation by MALDI-TOF/TOF mass spectrometry with high sensitivity and without the need to perform 2D HPLC separation of labelled peptides. The overall outcome is the simplification in the data complexity and the ease of use of the labelling protocol. PMID- 17724580 TI - Development and validation of a qualitative screening method for the detection of exogenous anabolic steroids in urine by liquid chromatography-tandem mass spectrometry. AB - A screening method for the urinary detection of 34 exogenous anabolic steroids has been developed. The method involves an enzymatic hydrolysis, liquid-liquid extraction and detection by liquid chromatography-tandem mass spectrometry. The use of some adducts such as [M+NH(4)](+), [M+CH(3)COO](-) and [M+H+MeOH](+) was necessary in order to detect some analytes at the required level (lower than 10 ng/ml). Two transitions were selected for each analyte. Different concentration factors have been studied in order to increase the sensitivity. A concentration factor of 50 was selected for the screening method although the high ion suppression observed under these conditions can hamper its application as a quantitative method. The method was validated and limits of detection were obtained by spiking ten different blank urine samples at five different concentration levels. Up to 29 analytes were detected in all spiked urines at the required level. Limits of detection between 1 and 10 ng/ml were obtained for most analytes which fulfil current requirements. The applicability of the method was shown by analysing positive samples. PMID- 17724581 TI - Changes in somatosensory-evoked potentials and high-frequency oscillations after paired-associative stimulation. AB - Paired-associative stimulation (PAS), combining electrical median nerve stimulation with transcranial magnetic stimulation (TMS) with a variable delay, causes long-term potentiation or depression (LTP/LTD)-like cortical plasticity. In the present study, we examined how PAS over the motor cortex affected a distant site, the somatosensory cortex. Furthermore, the influences of PAS on high-frequency oscillations (HFOs) were investigated to clarify the origin of HFOs. Interstimulus intervals between median nerve stimulation and TMS were 25 ms (PAS(25)) and 10 ms (PAS(10)). PAS was performed over the motor and somatosensory cortices. SEPs following median nerve stimulation were recorded before and after PAS. HFOs were isolated by 400-800 Hz band-pass filtering. PAS(25) over the motor cortex increased the N20-P25 and P25-N33 amplitudes and the HFOs significantly. The enhancement of the P25-N33 amplitude and the late HFOs lasted more than 60 min. After PAS(10) over the motor cortex, the N20-P25 and P25-N33 amplitudes decreased for 40 min, and the HFOs decreased for 60 min. Frontal SEPs were not affected after PAS over the motor cortex. PAS(25/10) over the somatosensory cortex did not affect SEPs and HFOs. PAS(25/10) over the motor cortex caused the LTP/LTD-like phenomena in a distant site, the somatosensory cortex. The PAS paradigms over the motor cortex can modify both the neural generators of SEPs and HFOs. HFOs may reflect the activation of GABAergic inhibitory interneurons regulating pyramidal neurons in the somatosensory cortex. PMID- 17724582 TI - Learning effects on muscle modes and multi-mode postural synergies. AB - We used the framework of the uncontrolled manifold hypothesis to explore the effects of practice on the composition of muscle groups (M-modes) and multi-M mode synergies stabilizing the location of the center of pressure (COP). In particular, we tested a hypothesis that practice could lead to a transition from co-contraction muscle activation patterns to reciprocal patterns. We also tested a hypothesis that new sets of M-modes would form stronger synergies stabilizing COP location. Subjects practiced load release tasks for five days while standing on a board with a narrow support surface (unstable board). Their M-modes and indices of multi-M-mode synergies were computed during standing without instability and during standing on an unstable board before practice, in the middle of practice, and at the end of practice. During standing without instability, subjects showed two consistent M-modes uniting dorsal and ventral muscles of the body respectively (reciprocal modes). While standing on an unstable board, prior to practice, subjects commonly showed M-modes uniting muscle pairs with opposing actions at major leg joints-co-contraction modes. Such sets of M-modes failed to stabilize the COP location in the anterior-posterior direction. Practice led to better task performance reflected in fewer incidences of lost balance. This was accompanied by a drop in the occurrence of co contraction M-modes and the emergence of multi-mode synergies stabilizing the COP location. We conclude that the central nervous system uses flexible sets of elemental variables (modes) to ensure stable trajectories of important performance variables (such as COP location). Practice can lead to adjustments in both the composition of M-modes and M-mode co-variation patterns resulting in stronger synergies stabilizing COP location. PMID- 17724584 TI - Use of Glubran 2 acrylic glue in interventional neuroradiology. AB - INTRODUCTION: Glubran 2 is a cyanoacrylate-based synthetic glue modified by the addition of a monomer synthesized by the manufacturer. With this material it is possible to obtain the stability of endovascular embolization that is needed to treat tumours and vascular disease. MATERIAL AND METHODS: We report our 3-year experience of the use of Glubran for treating extracerebral tumours, spinal tumours, spinal arteriovenous malformations, and brain and spine dural fistulae. Glubran 2 was diluted with Lipiodol and injected in a continuous column with the flow rate monitored by seriography. The injection was stopped when retrograde flow was displayed in the afferent vessel. RESULTS: There were no periprocedural or subsequent clinical complications and the glue resulted in successful selective permanent occlusion with intralesional penetration similar to the angiographic features of microcatheterization. CONCLUSIONS: The embolization procedure was technically straightforward and relatively safe. However, Glubran 2 can be difficult to use and the procedure does carry major risks for patients. Glue injection requires in-depth study of the lesion, its circulation and the collateral circulation to avoid severe complications due to inappropriate use. PMID- 17724583 TI - Visual and musculoskeletal underpinnings of anchoring in rhythmic visuo-motor tracking. AB - Anchoring, that is, a local reduction in kinematic (i.e., spatio-temporal) variability, is commonly observed in cyclical movements, often at or around reversal points. Two kinds of underpinnings of anchoring have been identified visual and musculoskeletal-yet their relative contributions and interrelations are largely unknown. We conducted an experiment to delineate the effects of visual and musculoskeletal factors on anchoring behavior in visuo-motor tracking. Thirteen participants (reduced to 12 in the analyses) tracked a sinusoidally moving visual target signal by making flexion-extension movements about the wrist, while both visual (i.e., gaze direction) and musculoskeletal (i.e., wrist posture) factors were manipulated in a fully crossed (3 x 3) design. Anchoring was affected by both factors in the absence of any significant interactions, implying that their contributions were independent. When gaze was directed to one of the target turning points, spatial endpoint variability at this point was reduced, but not temporal endpoint variability. With the wrist in a flexed posture, spatial and temporal endpoint variability were both smaller for the flexion endpoint than for the extension endpoint, while the converse was true for tracking with the wrist extended. Differential anchoring effects were absent for a neutral wrist posture and when gaze was fixated in between the two target turning points. Detailed analyses of the tracking trajectories in terms of velocity profiles and Hooke's portraits showed that the tracking dynamics were affected more by wrist posture than by gaze direction. The discussion focuses on the processes underlying the observed independent effects of gaze direction and wrist posture on anchoring as well as their implications for the notion of anchoring as a generic feature of sensorimotor coordination. PMID- 17724585 TI - Massive air embolism in a newborn. PMID- 17724586 TI - Postnatal clinical and imaging follow-up of infants with prenatal isolated mild ventriculomegaly: a series of 101 cases. AB - BACKGROUND: Postnatal imaging and clinical outcome of fetuses with isolated mild ventriculomegaly (IMV) have never been systematically analysed. OBJECTIVE: To evaluate the postnatal clinical outcomes of a large cohort of fetuses with IMV and to correlate them with pre- and postnatal imaging. MATERIALS AND METHODS: We report a prospective study of 101 fetuses with IMV (10-15 mm ventriculomegaly with otherwise normal US, MRI, karyotype and TORCH screening). IMV was divided into minor (10-11.9 mm) and moderate (12-15 mm) ventriculomegaly. Ventriculomegaly was considered uni- or bilateral, stable, progressive, regressive or resolved according to the prenatal US follow-up. Clinical follow-up was performed by a neuropaediatrician. Postnatal imaging included cranial US (n = 71) and MRI (n = 76). RESULTS: The outcome of minor and moderate IMV was excellent in 94% and 85% of infants, respectively. It was not different between uni- and bilateral IMV, and between stable, regressive and resolved IMV, and was independent of gestational age at diagnosis and gender. Fixed neurological abnormalities were observed in nine infants. Postnatal MRI showed white-matter abnormalities in 14 infants, including 6 of the 9 infants with a poor outcome. CONCLUSION: The prognosis was slightly better in minor IMV than in moderate IMV. Postnatal MRI showed white-matter abnormalities in two-thirds of the infants with a poor outcome. PMID- 17724587 TI - Production of poly-beta-hydroxybutyrate (PHB) by Alcaligenes latus from maple sap. AB - Maple sap, an abundant natural product especially in Canada, is rich in sucrose and thus may represent an ideal renewable feedstock for the production of a wide variety of value-added products. In the present study, maple sap or sucrose was employed as a carbon source to Alcaligenes latus for the production of poly-beta hydroxybutyrate (PHB). In shake flasks, the biomass obtained from both the sap and sucrose were 4.4 +/- 0.5 and 2.9 +/- 0.3 g/L, and the PHB contents were 77.6 +/- 1.5 and 74.1 +/- 2.0%, respectively. Subsequent batch fermentation (10 L sap) resulted in the formation of 4.2 +/- 0.3 g/L biomass and a PHB content of 77.0 +/ 2.6%. The number average molecular weights of the PHB produced by A. latus from maple sap and pure sucrose media were 300 +/- 66 x 10(3) and 313 +/- 104 x 10(3) g/mol, respectively. Near-infrared, (1)H magnetic resonance imaging (MRI), and (13)C-MRI spectra of the microbially produced PHB completely matched those obtained with a reference material of poly[(R)-3-hydroxybutyric acid]. The polymer was found to be optically active with [alpha](25) (D) equaled to -7.87 in chloroform. The melting point (177.0 degrees C) and enthalpy of fusion (77.2 J/g) of the polymer were also in line with those reported, i.e., 177 degrees C and 81 J/g, respectively. PMID- 17724588 TI - A simple but effective cancer vaccine consisting of an antigen and a cationic lipid. AB - Developing a cancer vaccine with a potent adjuvant, which is safe for human use, remains to be an unmet need. In this study, we developed a simple, safe, yet efficient, peptide-based therapeutic cancer vaccine, DOTAP/E7 complex, which comprises only two molecules: a DOTAP cationic lipid and a peptide antigen derived from E7 oncoprotein of human papillomavirus (HPV) type 16. The anti cancer activity of DOTAP/E7 against existing HPV positive TC-1 tumor was compared to that of our previous LPD/E7 formulation, which contains bacterial DNA CpG motifs. Tumor-bearing mice showed significant tumor inhibition following a single vaccination of either formulation at the optimal lipid dose, suggesting that DOTAP liposome alone can provide a potent adjuvant activity without plasmid DNA. E7 peptide formulated with DOTAP induced migration of activated dendritic cells (DC) to the draining lymph node (DLN) and efficiently generated functional antigen-specific CD8+ T lymphocyte responses. Accumulation of CD8+ tumor infiltrating T cells and apoptosis at tumor sites were observed after treatment with DOTAP/E7 complexes, which was also associated with a decreased amount of CD25(+)Foxp3(+) regulatory T cells in treated animals. Reactive oxygen species (ROS) induced by DOTAP cationic lipid in DLN revealed a plausible mechanism of the initial interaction between DC and DOTAP. An adequate amount of ROS generation was apparently required for the initiation of the vaccine mechanism; however, an overdose of DOTAP induced massive ROS production and apoptosis of DC in DLN, which led to diminished anti-cancer immunity. Overall, these results indicate that cationic lipid DOTAP alone serves as an efficient vaccine adjuvant for the induction of a therapeutic, antigen-specific anti-cancer activity. PMID- 17724590 TI - Polyetheretherketone (PEEK) cage filled with bone morphogenic protein and demineralised bone matrix in anterior cervical discectomy and fusion. PMID- 17724589 TI - The absence of invariant chain in MHC II cancer vaccines enhances the activation of tumor-reactive type 1 CD4+ T lymphocytes. AB - Activation of tumor-reactive T lymphocytes is a promising approach for the prevention and treatment of patients with metastatic cancers. Strategies that activate CD8(+) T cells are particularly promising because of the cytotoxicity and specificity of CD8(+) T cells for tumor cells. Optimal CD8(+) T cell activity requires the co-activation of CD4(+) T cells, which are critical for immune memory and protection against latent metastatic disease. Therefore, we are developing "MHC II" vaccines that activate tumor-reactive CD4(+) T cells. MHC II vaccines are MHC class I(+) tumor cells that are transduced with costimulatory molecules and MHC II alleles syngeneic to the prospective recipient. Because the vaccine cells do not express the MHC II-associated invariant chain (Ii), we hypothesized that they will present endogenously synthesized tumor peptides that are not presented by professional Ii(+) antigen presenting cells (APC) and will therefore overcome tolerance to activate CD4(+) T cells. We now report that MHC II vaccines prepared from human MCF10 mammary carcinoma cells are more efficient than Ii(+) APC for priming and boosting Type 1 CD4(+) T cells. MHC II vaccines consistently induce greater expansion of CD4(+) T cells which secrete more IFNgamma and they activate an overlapping, but distinct repertoire of CD4(+) T cells as measured by T cell receptor Vbeta usage, compared to Ii(+) APC. Therefore, the absence of Ii facilitates a robust CD4(+) T cell response that includes the presentation of peptides that are presented by traditional APC, as well as peptides that are uniquely presented by the Ii(-) vaccine cells. PMID- 17724591 TI - Impact of iliac crest bone graft harvesting on fusion rates and postoperative pain during instrumented posterolateral lumbar fusion. AB - This study aims to evaluate the influence of bone harvesting on postoperative pain and fusion rates. Group 1 patients received iliac crest bone graft (ICBG) either alone or augmented with local bone. Group 2 received only local bone. No statistical significance was found in radiological union or in the Oswestry Disability Index scores. Visual Analogue Scale scores showed less pain in group 2. Logistic regression showed no correlation between residual pain and occurrence of fusion. Harvesting ICBG did not appear to increase fusion rates and no relation was found between radiological non-union and pain. PMID- 17724592 TI - Comment on Changulani et al. "Comparison of the use of the humerus intramedullary nail and dynamic compression plate for the management of diaphyseal fractures of the humerus. A randomised controlled study". PMID- 17724594 TI - Arthroscopic treatment of symptomatic type D medial plica. AB - We aimed to review the results of subtotal arthroscopic resection of symptomatic type D medial plica. We retrospectively evaluated 23 knees with symptomatic type D medial plica in 22 patients without other intra-articular pathology. All patients complained of chronic knee pain that had not been alleviated by medical treatment or physical therapy. In only three (13%) of the patients studied was the plica diagnosed pre-operatively with magnetic resonance imaging. The type D medial plicae in our series were classified as fenestrated (14 knees), torn (5 knees), or reduplicated (4 knees). Fibrotic changes in the plicae and degenerative changes on the medial femoral condyle were found in 16 knees Patellofemoral chondromalacia was present in three knees Arthroscopic partial resection was performed in all patients. Comparative Lysholm Knee Scale scores before and after surgery revealed a significant clinical improvement (pre operative status, 67.19 +/- 8.05 vs. post-operative status, 90.57 +/- 9.80; P < 0.001). Type D medial plica should be considered as a possible cause of chronic knee pain. Arthroscopic partial resection of the plicae in symptomatic patients gives satisfactory results. PMID- 17724595 TI - Is radial shortening useful for Litchman stage 3B Kienbock's disease? AB - Treatment of Litchman stage 3 Kienbock's disease is still controversial. In this study our aim was to evaluate the effectiveness of radial shortening on stage 3B Kienbock's disease in comparison with stage 3A cases. Radial shortening was performed for 23 patients who had stage 3A (group I, n = 13) and 3B (group II, n = 10) Kienbock's disease between 1994 and 2004. The radial osteotomy was performed 4.5 cm proximal to the distal articular surface. The mean shortening was 2.6 mm (range 2 to 4.5). The average follow-up period was 85 months (range 26 147). Based on the modified Nakamura system, the mean clinical points were 14.3 in group I and 13.3 in group II. There was no statistical difference between both groups with regard to clinical points (P = 0.483). The extension-flexion arc showed significant improvement in both groups. Based on the results of this long term follow-up study, we concluded that radial shortening osteotomy can be performed in the treatment of type 3B Kienbock's disease as reliably as type 3A, despite the lack of evident radiological improvement. PMID- 17724593 TI - Functional outcome following excision of a tumour and reconstruction of the distal radius. AB - We retrospectively studied the functional and oncological results of 15 patients after reconstruction of the distal radius with osteoarticular allograft or non vascularised fibular graft following wide excision of an aggressive benign or malignant tumour. Eight patients underwent osteoarticular allograft and seven patients had a non-vascularised autogenous fibular graft reconstruction. The average time for incorporation of the graft was 6 and 5 months in each reconstruction respectively. There was no tumour recurrence after follow up over 41.5-95.5 (average 60.5) months. All patients had good and excellent functional results. Three patients in the group reconstructed with osteoarticular allograft had plate loosening and graft fractures which were successfully treated subsequently. PMID- 17724596 TI - Ciprofloxacin inhibits lipopolysaccharide-induced toll-like receptor-4 and 8 expression on human monocytes derived from adult and cord blood. PMID- 17724597 TI - Extramedullary, extranodal lymphoplasmacytic lymphoma with macroglobulinemia: long-term complete remission with fludarabine. PMID- 17724598 TI - Revelation of ancestral roles of KNOX genes by a functional analysis of Physcomitrella homologues. AB - KNOX genes are indispensable elements of indeterminate apical growth programmes of vascular plant sporophytes. Since little is known about the roles of such genes in non-vascular plants, functional analysis of moss KNOX homologues (MKN genes) was undertaken using the genetically amenable model plant, Physcomitrella patens. Three MKN genes were inactivated by targeted gene knockout to produce single, double and triple mutants. MKN2 (a class 1 KNOX gene) mutants were characterised by premature sporogenesis, abnormal sporophyte ontogeny and irregular spore development. MKN4 (a second class 1 gene) mutants were phenotypically normal. MKN1-3 (a class 2 KNOX gene) mutants exhibited defects in spore coat morphology. Analysis of double and triple mutants revealed that the abnormal sporophytic phenotype of MKN2 mutants was accentuated by mutating MKN4 and to a lesser degree by mutating MKN1-3. The aberrant spore phenotype of MKN1-3 and MKN2 mutants was exacerbated by mutating MKN4. This study provides the first instance in which an abnormal phenotype has been associated with the disruption of a class 2 KNOX gene as well as the first demonstrated case of functional redundancy between a class 1 and a class 2 KNOX gene. We conclude that KNOX genes play significant roles in programming sporophytic development in moss and we provide evidence that ancestral function(s) of this gene family were instrumental in the successful transition of plants to a terrestrial environment. PMID- 17724599 TI - Ultradian cycles in mice: definitions and links with REMS and NREMS. AB - Sleep can be organized in two quite different ways across homeothermic species: either in one block (monophasic), or in several bouts across the 24 h (polyphasic). Yet, the main relationships between variables, as well as regulating mechanisms, are likely to be similar. Correlations and theories on sleep regulation should thus be examined on both types of sleepers. In previous studies on monophasic humans, we have shown preferential links between the number of ultradian cycles and the rapid eye movement sleep (REMS) time, rather than with its counterpart non-rapid eye movement sleep (NREMS). Here, the sleep of 26 polyphasic mice was examined, both to better describe the NREMS distribution, which is far more complex than in humans, and to replicate the analyses performed on humans. As in humans, the strongest links with the number of cycles were with REMS. Links were not significant with NREMS taken as a whole, although positive correlations were found with the NREMS immediately preceding REMS episodes and inversely significant with the residue. This convergence between monophasic and polyphasic patterns supports the central role played by REMS in sleep alternation. PMID- 17724600 TI - Absorption of copper and copper-histidine complexes across the apical surface of freshwater rainbow trout intestine. AB - Bioavailability is integral in mediating the delicate balance between nutritive and potentially toxic levels of copper in fish diets. Brush-border membrane vesicles isolated from freshwater rainbow trout intestine were used to characterise apical copper absorption, and to examine the influence of the amino acid histidine on this process. In the absence of histidine, a low affinity, high capacity copper uptake mechanism was described. However, when expressed as a function of ionic copper (Cu(2+)), absorption was linear, rather than saturable, suggesting that the saturable curve was an artifact of copper speciation. Conversely, in the presence of L: -histidine (780 microM) saturable uptake was characterised. The uptake capacity discerned (J (max) of 354 +/- 81 nmol mg protein(-1) min(-1)) in the presence of histidine indicated a significantly reduced capacity for copper transport than that in the absence of histidine. To determine if copper uptake was achievable through putative histidine uptake pathways, copper and histidine were incubated in the presence of tenfold greater concentrations of amino acids proposed to block histidine transporters. Accounting for changes in copper speciation, significant inhibition of uptake by glycine and lysine were noted at copper levels of 699 and 1,028 microM. These results suggest that copper-histidine complexes may be transportable via specific amino acid-transporters in the brush-border membrane. PMID- 17724601 TI - Synchronous gastric cancer in primary sporadic colorectal cancer patients in Korea. AB - BACKGROUND AND AIMS: Colorectal cancer has been reported to be the malignancy most frequently associated with gastric cancer in Korea. The aim of this study was to define the frequency and clinical characteristics of synchronous gastric cancer detected at preoperative esophagogastroduodenoscopy (EGD) in colorectal cancer patients. MATERIALS AND METHODS: This prospective study analyzed the EGD results from 1,542 consecutive colorectal cancer patients who underwent surgery from January 2003 to December 2005 at the Center for Colorectal Cancer, National Cancer Center, Korea. RESULTS: Of the 1,542 cases, 1,155 (74.9%) underwent EGD at our center and 387 underwent EGD at other hospitals within 6 months before surgery. Of the 1,542 cases, synchronous gastric cancers were detected in 31 cases (2.0%). Of these 31 cases, 26 had early gastric cancer (EGC; 83.9%) and 5 had advanced gastric cancer. Ten (38.5%) of the 26 EGC cases were managed using endoscopic mucosal resection. Compared to colorectal cancer patients without synchronous gastric cancer, the group of patients with synchronous gastric cancer was older (65.5+/-9.6 vs 58.4+/-11.3 years, p=0.001) and had a greater proportion of males (77.4 vs 59.4%, p=0.043). CONCLUSION: This study found that 2% of Korean sporadic colorectal cancer patients had synchronous gastric cancer. A preoperative EGD for colorectal cancer patients is likely to greatly assist in the diagnosis of synchronous gastric cancer at an early stage and the implementation of appropriate minimally invasive treatment. PMID- 17724602 TI - Induction of PDGF-B in TCA-treated epidermal keratinocytes. AB - Trichloroacetic acid (TCA) is one of the most widely used peeling agents, and induces full necrosis of the whole epidermis, followed by reconstitution of the epidermis and the matrix of the papillary dermis. The cytotoxic effects of TCA, such as suppressing proliferation of keratinocytes and fibroblasts and protein synthesis by fibroblasts, have already been reported. However, the entire biological mechanism responsible for TCA peeling has yet to be determined. Hypothetical activation effects of TCA treatment on epidermal cells to induce production of growth factors and cytokines are examined, and are compared with its cytotoxic effects in terms of time course and applied TCA concentrations. After various periods of incubation with TCA, viability of Pam212 murine keratinocytes was investigated with MTT assay and dye exclusion assay, and production of growth factors and cytokines with reverse transcription-polymerase chain reaction (RT-PCR). Changes in platelet-derived growth factor (PDGF)-B mRNA expression and protein production in the human skin specimens after TCA application were then examined by RT-PCR and immunohistochemistry, respectively. Incubation with TCA showed cytotoxicity and induced death of Pam212 cells, depending on the incubation period and the TCA concentration. In addition, expressions of PDGF-B, tumor growth factor (TGF)-alpha, TGF- beta1 and vascular endothelial growth factor, which are the growth factors reportedly secreted from keratinocytes during wound healing, were all detected in Pam212 cells after short term treatment with TCA. Expressions of inflammatory cytokines such as interleukin (IL)-1 and IL-10 were also induced. In TCA-treated NIH-3T3 fibroblasts, in contrast, observed was upregulation of only keratinocyte growth factor, which is reportedly secreted from fibroblasts, as well as the similar cytotoxic effect. In human skin, PDGF-B mRNA expression became significantly upregulated after TCA application, and then immediately downregulated. Immunoreactive PDGF-B in the cytoplasm of keratinocytes became detectable throughout the epidermis after TCA application, reached maximum after the peak of mRNA expression, and then declined significantly over 24 h when the epidermis became completely necrotic. The TCA-treated epidermis acts as a major source of growth factors, including PDGF-B, before undergoing full necrosis. This effect might contribute to a promotion of re-epithelialization and dermal regeneration without wound contraction and scarring. PMID- 17724603 TI - The impact of different closure materials on pharyngeal wound healing: an experimental animal study. AB - The formation of pharyngo-cutaneous fistula (PCF) is controversial and various predisposing factors have been proposed. This study aimed to compare different suture materials in the closure of pharyngeal wounds in experimental animals. Fifty-two Sprague-Dawley rats were divided into three groups. Artificial pharyngotomy was performed and was then repaired with Vicryl, polypropylene, and Vicryl plus fibrin glue, respectively. Outcome measurements included gross wound inspection and histological examination. There was a significant difference in the rates of PCF formation between group I and group II (Fisher's exact test, p = 0.046). In addition, minimal inflammatory response was found in the polypropylene group when compared to the other groups. The fibrin glue-treated group had the highest fibroblast activity and collagen deposition. Polypropylene produced minimal tissue reaction, which facilitated the healing process. Therefore, proper selection of suture material can probably reduce the rate of PCF but should not be substituted for proper aseptic and meticulous surgical techniques. PMID- 17724604 TI - Obstructive site localization using multisensor manometry versus the Friedman staging system in obstructive sleep apnea. AB - The aim of this study was to find the correlation between an anatomy-based staging system and pressure manometry performed during sleep. A retrospective study of 45 patients with obstructive sleep apnea (OSA) was carried out. All patients were evaluated by polysomnography, and obstruction sites were localized using a multisensor manometer during the full night. Obstruction sites were classified into retropalatal and retroglossal. The patients were also staged by anatomic findings of tonsil size and palate position. The % retroglossal obstruction was 29.4, 33.5 and 48.6% in stages I, II and III, respectively. There was no significant difference between stages. In contrast, when compared according to the Friedman tongue position (FTP), the mean % retroglossal obstruction of FTP grade 3 was significantly higher than that of FTP grade 1 (P = 0.009) although apnea hypopnea index, body mass index and lowest SpO2 were not different among FTP grades. It seems that FTP correlates with retroglossal obstruction and may be used to select patients in need of retroglossal modification of the airway. PMID- 17724605 TI - Does the prevalence of otolaryngological diseases in deaf children differ from children without hearing impairment? AB - There is no enough data about the prevalence of otorhinolaryngological (ORL) diseases in deaf children. In this study, we aimed to determine the prevalence of ORL diseases among deaf children and compare children from a school for the deaf with those attending regular primary schools for the presence of ear, nose and throat (ENT) problems. The subjects were 1,282 children attending three primary schools in the province of Duzce and 572 hearing-impaired children from eight schools for the deaf. Following ENT examinations, ORL findings were statistically compared between two groups using a Chi-square test and P values less than 0.05 were considered significant. Upper airway pathologies including chronic tonsillitis, rhinitis, septal deviation and tubal dysfunction, and chronic otitis media (COM) were found to be statistically higher in deaf children than in children without hearing impairment. Although the incidence of middle ear effusion was found to be higher in deaf children, it was not statistically significant. On the other hand, the incidence of impacted wax was lower in deaf children than others. In conclusion, we should have enough data on the prevalence of ORL diseases in deaf children to give a clue to help prevent ORL diseases and if we can detect them early, we can solve the problems before they become more complicated and we can rehabilitate these children better. PMID- 17724606 TI - Morphology and function of Bast's valve: additional insight in its functioning using 3D-reconstruction. AB - The utriculo-endolymphatic valve was discovered by Bast in 1928. The function of Bast's valve is still unclear. By means of orthogonal-plane fluorescence optical sectioning (OPFOS) microscopy 3D-reconstructions of the valve and its surrounding region are depicted. The shape of the duct at the utricular side is that of a flattened funnel. In the direction of the endolymphatic duct and sac this funnel runs into a very narrow duct. The valve itself has a rigid 'arch-like' configuration. The opposing thin, one cell-layer thick, utricular membrane is highly compliant. We propose that opening and closure of the valve occurs through movement of the flexible base/utricular membrane away from and toward the relatively rigid valve lip. PMID- 17724607 TI - Simultaneous detection of eight cytokines in human dermal wounds with a multiplex bead-based immunoassay for wound age estimation. AB - We performed quantification of IL 2, IL 4, IL 6, IL 8, IL 10, GM-CSF, IFN gamma, and TNF alpha in human dermal wounds for wound age estimation. The proliferation of dermal cells and infiltration of inflammatory cells were also analyzed. Neutrophils and macrophages were detected from 2 h post-injury, and strong infiltrations were seen at 33-49 h. T and B lymphocytes also infiltrated simultaneously from 71 h. Strong proliferation of fibroblasts were shown from 246 h, and thickening of the epidermis from 71 h. IL 10, GM-CSF, IFNgamma, and TNF alpha increased from the early phase of dermal wound healing, IL 6 exclusively in the middle phase, IL 2, IL 4, and IL 8 from the middle phase to the late phase. Among the cytokines analyzed in the present study, IL 6, IL 8, IFNgamma, and TNF alpha were strongly expressed. Results of the present study suggest that multiplex cytokine analysis at the wound site can be useful for wound age estimation. In addition, multiplex data obtained from the same sample with a single method would demonstrate more accurate interactions of cytokines during dermal wound healing. Although the present study was oriented to practical forensic pathology, the data obtained would be informative for various fields of medicine. PMID- 17724608 TI - Chromium in exhaled breath condensate and pulmonary tissue of non-small cell lung cancer patients. AB - OBJECTIVE: Chromium in exhaled breath condensate (EBC) has recently been proposed as a biomarker of pulmonary exposure. The aim of this study was to measure the Cr levels in the EBC and pulmonary tissue of patients with early, operable non-small cell lung cancer (NSCLC) who had not been occupationally exposed to Cr before and after tumour resection and to correlate Cr in lung tissue with that in EBC. METHODS: Cr levels in the EBC and pulmonary tissue of 20 NSCLC patients were measured by means of electrothermal atomic absorption before and after tumour resection. Cr levels were also measured in the urine of 15 of these patients. RESULTS: The pre-surgery EBC Cr levels of the NSCLC patients were not different from those of the controls, but both EBC and urinary Cr levels increased after surgery. There was a significant correlation between Cr levels in EBC and pulmonary tissue (R = 0.55, P = 0.01), but not between these and urinary Cr levels. CONCLUSION: Cr levels in EBC and urine of NSCLC patients were increased after surgical intervention. Measured Cr EBC levels were by one order of magnitude lower than those observed in moderately exposed workers. This fact, together with the correlation between Cr in EBC and in pulmonary tissue, confirms that EBC is a promising biological fluid to test pulmonary exposure to Cr, giving complementary information to that provided by urinary Cr, not correlated with EBC and tissue. PMID- 17724609 TI - Non-uniform changes in magnetic resonance measurements of the semitendinosus muscle following intensive eccentric exercise. AB - This study was designed to determine the regional differences of magnetic resonance (MR) measurements in the hamstrings [biceps femoris muscle long head (BFl) and short head (BFs), semimembranosus muscle (SM), and semitendinosus muscle (ST)] following eccentric knee-flexion exercise. Twelve male volunteers performed eccentric knee-flexion exercise. Maximum isometric torque, plasma creatine kinase (CK) activity, muscle soreness, and MR images of the hamstrings were measured before and immediately following exercise, and on the first, second, third and seventh days following the exercise. Cross-sectional areas (CSAs) and transverse relaxation times (T2s) of the hamstrings were measured from the T2-weightened MR imaging sequences of 30% (proximal), 50% (middle), and 70% (distal) areas of the thigh length. The CSA of the ST at proximal and middle regions had significantly increased on the third day, but no significant changes were found for the BFl or SM. Immediately following exercise, T2 values had increased significantly in the BFs, BFl, and ST. On the third day, T2 values of only ST increased significantly at proximal, middle and distal regions. Significant differences of T2 values between proximal and distal regions in the ST were found for the second, third and seventh days following the exercise. These results suggest that because of the anatomical characteristics of the muscles, the degrees of response following the exercise differed among the muscles and the regions of ST muscle. PMID- 17724610 TI - Effects of exercise intensity and duration on fat metabolism in trained and untrained older males. AB - Advancing age is associated with changes in fat and carbohydrate (CHO) metabolism, which is considered a risk factor for cardiovascular disease and diabetes. The effects of exercise intensity and duration on fat and CHO metabolism in elderly male subjects were investigated in the present study. Seven trained (63.7+/-4.7 years) and six untrained (63.5+/-4.5 years) healthy males performed three 30 min trials on a cycle ergometer at 50, 60 and 70% VO2max and two other trials at 60 and 70% VO2max in which the total energy expenditure was equal to that for 30 min at 50% VO2max Respiratory measures were undertaken throughout the exercise and blood samples taken before and immediately after each trial. Statistical analyses revealed a significant effect of exercise intensity on fat oxidation when the exercise durations were equated as well as when the energy expenditure was held constant for the three trials, though no training effect was noted. Total carbohydrate oxidation increased significantly with exercise intensity (P<0.05) and with training. Significantly higher levels of non esterified free fatty acid (NEFA) and glycerol were observed for trained compared with untrained though not for B-hydroxybutyrate (3-OH) or insulin. No differences in NEFA, glycerol, 3-OH were evident for increases in exercise intensity. Carbohydrate and fat oxidation are significantly affected by exercise intensity in elderly males, although only CHO oxidation is influenced by training. Furthermore, training-induced increases in the availability of NEFA and glycerol are not associated with an increase in fat oxidation, rather an increase in CHO oxidation. PMID- 17724611 TI - Two alloalleles of Xenopus laevis hairy2 gene--evolution of duplicated gene function from a developmental perspective. AB - Gene duplication is a fundamental source of a new gene in the process of evolution. A duplicated gene is able to accept many kinds of mutations that could lead to loss of function or novel phenotypic diversity. Alternatively, the duplicated genes complementarily lose part of their functions to play original roles as a set of genes, a process called subfunctionalization. Pseudotetraploid frog Xenopus laevis has four sets of genes, and it is generally thought that the alloalleles in X. laevis have mutually indistinguishable functions. In this paper, we report differences and similarities between Xhairy2a and Xhairy2b in the neural crest, floor plate, and prechordal plate. Knockdown studies showed that Xhairy2a seems not to function in the neural crest, although both of them are required in the floor plate and the prechordal plate. Temporal expression pattern analysis revealed that Xhairy2a is a maternal factor having lower zygotic expression than Xhairy2b, while Xhairy2b is not loaded in the egg but has high zygotic expression. Spatial expression pattern analysis demonstrated that future floor plate expression is shared by both alloalleles, but Xhairy2b expression in the neural crest is much higher than Xhairy2a expression, consistent with the results of individual knockdown experiments. Therefore, our data suggest that subfunctionalization occurs in Xhairy2. PMID- 17724612 TI - Carbonic anhydrase 9 (CA9) expression in tumor cells enhances sensitivity to tirapazamine. AB - PURPOSE: Carbonic anhydrase 9 (CA9) is over-expressed in many human solid tumors under conditions of low oxygen concentration and can be associated with a low probability of survival. In this study, stable CA9-expressing cell lines were established using the CA9 gene-defective human C33a cell line and the HeLa cell line to investigate the role of CA9 in response to ionizing radiation and hypoxia selective cytotoxin, Tirapazamine (TPZ). METHODS AND MATERIALS: Human CA9 cDNA or an empty vector was transfected into the C33a and HeLa cell lines and C33a vector, C33a-CA9, HeLa-vector, and HeLa-CA9 cell lines were produced accordingly. Sensitivity of the C33a-vector/C33a-CA9 cells to ionizing radiation and TPZ was measured using clonogenic assays. The alkaline comet assay was used to measure single strand DNA breaks caused by TPZ in the C33a-vector, C33a-CA9, HeLa-vector, and HeLa-CA9 cell lines. RESULTS: Radiation sensitivity, as determined with clonogenic survival assays, of C33a-vector/C33a-CA9 cells did not differ under either normoxic or hypoxic conditions. However, increased clonogenic sensitivity to TPZ was observed in C33a-CA9 cells under the hypoxic condition by 26% (95% CI 14-39%, P = 0.02 in comparison to the C33a-vector cells). The comet assay showed significantly greater DNA damage in the C33a-CA9 cells compared with that of the C33a-vector cells with the same treatment under hypoxic conditions, supporting the results of the clonogenic survival data. Because this difference in the amount of DNA damage was not observed for the hypoxic HeLa-CA9/HeLa-vector cell lines, both of which have induced CA9 expression by hypoxia, the enhanced sensitivity of C33a-CA9 cells to TPZ is considered to be due to the specific condition of CA9 over-expression. CONCLUSION: Our results suggest the possibility that CA9 over-expression in tumors might be exploited to increase the treatment effects of TPZ. PMID- 17724613 TI - Transcriptome profiling, sequence characterization, and SNP-based chromosomal assignment of the EXPANSIN genes in cotton. AB - The knowledge of biological significance associated with DNA markers is very limited in cotton. SNPs are potential functional marker to tag genes of biological importance. Plant expansins are a group of extracellular proteins that directly modify the mechanical properties of cell walls, enable turgor-driven cell extension, and likely affect length and quality of cotton fibers. Here, we report the expression profiles of EXPANSIN transcripts during fiber elongation and the discovery of SNP markers, assess the SNP characteristics, and localize six EXPANSIN A genes to chromosomes. Transcriptome profiling of cotton fiber oligonucleotide microarrays revealed that seven EXPANSIN transcripts were differentially expressed when there was parallel polar elongation during morphogenesis at early stage of fiber development, suggesting that major and minor isoforms perform discrete functions during polar elongation and lateral expansion. Ancestral and homoeologous relationships of the six EXPANSIN A genes were revealed by phylogenetic grouping and comparison to extant A- and D-genome relatives of contemporary AD-genome cottons. The average rate of SNP per nucleotide was 2.35% (one SNP per 43 bp), with 1.74 and 3.99% occurring in coding and noncoding regions, respectively, in the selected genotypes. An unequal evolutionary rate of the EXPANSIN A genes at the subgenome level of tetraploid cotton was recorded. Chromosomal locations for each of the six EXPANSIN A genes were established by gene-specific SNP markers. Results revealed a strategy for discovering SNP markers in a polyploidy species like cotton. These markers could be useful to associate candidate genes with the complex fiber traits in MAS. PMID- 17724615 TI - Rain, prey and predators: climatically driven shifts in frog abundance modify reproductive allometry in a tropical snake. AB - To predict the impacts of climate change on animal populations, we need long-term data sets on the effects of annual climatic variation on the demographic traits (growth, survival, reproductive output) that determine population viability. One frequent complication is that fecundity also depends upon maternal body size, a trait that often spans a wide range within a single population. During an eight year field study, we measured annual variation in weather conditions, frog abundance and snake reproduction on a floodplain in the Australian wet-dry tropics. Frog numbers varied considerably from year to year, and were highest in years with hotter wetter conditions during the monsoonal season ("wet season"). Mean maternal body sizes, egg sizes and post-partum maternal body conditions of frog-eating snakes (keelback, Tropidonophis mairii, Colubridae) showed no significant annual variation over this period, but mean clutch sizes were higher in years with higher prey abundance. Larger females were more sensitive to frog abundance in this respect than were smaller conspecifics, so that the rate at which fecundity increased with body size varied among years, and was highest when prey availability was greatest. Thus, the link between female body size and reproductive output varied among years, with climatic factors modifying the relative reproductive rates of larger (older) versus smaller (younger) animals within the keelback population. PMID- 17724614 TI - cAMP-response element binding protein (CREB) regulates cyclosporine-A-mediated down-regulation of cathepsin B and L synthesis. AB - Cyclosporin A (CsA) is an immunosuppressant with severe side effects including gingival overgrowth. We have previously reported that CsA impairs the activity of the lysosomal enzymes cathepsin B and L in human gingival fibroblasts (HGFs). Here, we have examined the effects of CsA on the DNA-binding activity of the cyclic AMP response element-binding protein (CREB) and cell viability, and the effects of CREB on cathepsin B and L synthesis and activity in HGFs. We have confirmed that CsA down-regulates cathepsin B and L synthesis. Further, CsA has no effect on cell viability and dramatically impairs CREB-DNA binding activity. Importantly, the synthesis of cathepsin B and L is down-regulated, and their activity is also significantly impaired in HGFs transfected with plasmid expressing dominant-negative CREB. These results suggest that CREB is essential for the CsA-mediated down-regulation of cathepsin B and L synthesis in HGFs. PMID- 17724616 TI - Comparative performance of invasive and native Celastrus species across environmental gradients. AB - The ability to understand and predict the success of invasive plant species in their new ranges is increased when there is a sympatric native congener available for comparison. Celastrus orbiculatus (oriental bittersweet) is a liana introduced into the United States in the mid-1800s from East Asia as an ornamental plant. Its native congener, Celastrus scandens (American bittersweet), ranges from the east coast of the United States as far west as Wyoming. In the Northeastern United States, C. orbiculatus is continuing to expand its range while C. scandens appears to be in serious decline. One hypothesis for this decline is that C. scandens does not have such a wide range of ecological tolerances in the current landscape as C. orbiculatus, which seems to tolerate a greater range of resource conditions. To investigate this hypothesis, we transplanted these two species into ten sites that spanned a full range of light and soil moisture conditions to compare their establishment and performance in terms of aboveground growth (biomass and height) and mortality. After two years, C. orbiculatus showed significantly lower mortality and greater biomass across all resource conditions compared to C. scandens. In addition, C. orbiculatus preferred more mesic soil moisture conditions, while C. scandens performed better in drier soil moisture conditions. Since much of the Northeastern United States is now forested, this preference for mesic soil conditions could make it more successful than C. scandens in the region. This study shows the utility of manipulative experiments, particularly those using congeneric native species as benchmarks, for assessing the causes and predicting the course of invasions. PMID- 17724617 TI - Microbial responses to nitrogen addition in three contrasting grassland ecosystems. AB - The effects of global N enrichment on soil processes in grassland ecosystems have received relatively little study. We assessed microbial community response to experimental increases in N availability by measuring extracellular enzyme activity (EEA) in soils from three grasslands with contrasting edaphic and climatic characteristics: a semiarid grassland at the Sevilleta National Wildlife Refuge, New Mexico, USA (SEV), and mesic grasslands at Konza Prairie, Kansas, USA (KNZ) and Ukulinga Research Farm, KwaZulu-Natal, South Africa (SAF). We hypothesized that, with N enrichment, soil microbial communities would increase C and P acquisition activity, decrease N acquisition activity, and reduce oxidative enzyme production (leading to recalcitrant soil organic matter [SOM] accumulation), and that the magnitude of response would decrease with soil age (due to higher stabilization of enzyme pools and P limitation of response). Cellulolytic activities followed the pattern predicted, increasing 35-52% in the youngest soil (SEV), 10-14% in the intermediate soil (KNZ) and remaining constant in the oldest soil (SAF). The magnitude of phosphatase response did not vary among sites. N acquisition activity response was driven by the enzyme closest to its pH optimum in each soil: i.e., leucine aminopeptidase in alkaline soil, beta N-acetylglucosaminidase in acidic soil. Oxidative enzyme activity varied widely across ecosystems, but did not decrease with N amendment at any site. Likewise, SOM and %C pools did not respond to N enrichment. Between-site variation in both soil properties and EEA exceeded any treatment response, and a large portion of EEA variability (leucine aminopeptidase and oxidative enzymes), 68% as shown by principal components analysis, was strongly related to soil pH (r = 0.91, P < 0.001). In these grassland ecosystems, soil microbial responses appear constrained by a molecular-scale (pH) edaphic factor, making potential breakdown rates of SOM resistant to N enrichment. PMID- 17724618 TI - Past climate changes and ecophysiological responses recorded in the isotope ratios of saguaro cactus spines. AB - The stable isotope composition of spines produced serially from the apex of columnar cacti has the potential to be used as a record of changes in climate and physiology. To investigate this potential, we measured the delta(18)O, delta(13)C and F(14)C values of spines from a long-lived columnar cactus, saguaro (Carnegiea gigantea). To determine plant age, we collected spines at 11 different heights along one rib from the stem apex (3.77 m height) to the base of a naturally occurring saguaro. Fractions of modern carbon (F(14)C) ranged from 0.9679 to 1.5537, which is consistent with ages between 1950 and 2004. We observed a very strong positive correlation (r = 0.997) between the F(14)C age of spines and the age of spines determined from direct and repeated height measurements taken on this individual over the past 37 years. A series of 96 spines collected from this individual had delta(18)O values ranging from 38 per thousand to 50 per thousand [Vienna standard mean ocean water (VSMOW)] and delta(13)C values from -11.5 per thousand to -8.5 per thousand [Vienna Peedee belemnite (VPDB)]. The delta(18)O and delta(13)C values of spines were positively correlated (r = 0.45, P < 0.0001) and showed near-annual oscillations over the approximately 15-year record. This pattern suggests that seasonal periods of reduced evaporative demand or greater precipitation input may correspond to increased daytime CO(2) uptake. The lowest delta(18)O and delta(13)C values of spines observed occurred during the 1983 and 1993 El Nino years, suggesting that the stable isotope composition recorded in spine tissue may serve as a proxy for these climate events. We compared empirical models and data from potted experimental cacti to validate these observations and test our hypotheses. The isotopic records presented here are the first ever reported from a chronosequence of cactus spines and demonstrate that tissues of columnar cacti, and potentially other long-lived succulents, may contain a record of past physiological and climatic variation. PMID- 17724619 TI - Limited impact of elevated levels of polyphenol oxidase on tree-feeding caterpillars: assessing individual plant defenses with transgenic poplar. AB - Polyphenol oxidase (PPO) is commonly believed to function as an effective antiherbivore defense in plants. PPO is induced in plants following herbivory, and insect performance is often negatively correlated with PPO levels. However, induced defenses create numerous changes in plants, and very little work has been done to test the direct effects of PPO on insect herbivores separately from other changes. This study examined the impacts of high levels of PPO on the performance of two species of tree-feeding caterpillars (Lymantria dispar and Orgyia leucostigma) on poplar. Transgenic PPO-overexpressing poplar (Populus tremula x Populus alba) was used as a source of elevated-PPO leaves, thereby controlling for the multiple effects of induction. In addition, the impacts of treating poplar foliage with high levels of purified mushroom PPO were examined on the two caterpillar species. Contrary to expectation, in several cases increased PPO levels had no significant effect on insect consumption or growth rates. Although one of the mechanisms by which PPO is believed to impact herbivores is via increased oxidative stress, the ingestion of large amounts of PPO had little or no effect on semiquinone radical and oxidized protein levels in the gut contents of lymantriid caterpillars. PPO activity in caterpillars is likely limited by the low oxygen and high ascorbate levels commonly found in their gut contents. This study questions whether induced PPO functions as an effective post-ingestive defense against tree-feeding caterpillars, and indicates that controlled, mechanistic studies are needed in other plant-herbivore systems to test for a direct effect of PPO on insect performance. PMID- 17724620 TI - Measurement of oral mucositis in children: a review of the literature. AB - GOALS OF WORK: The assessment of oral mucositis is important. There is a paucity of validated oral mucositis assessment instruments for use in children. This paper reviews the available mucositis measurement tools and their applicability to a paediatric population. MATERIALS AND METHODS: Literature search of PUBMED and bibliography searches identified articles relevant to mucositis measurement tools and the measurement of mucositis in paediatrics. RESULTS: The relevant issues in the literature could be grouped into three categories: (1) development and evaluation of oral assessment tools, (2) oral assessment in the paediatric population, and (3) challenges to the assessment of oral mucositis in children. There were numerous validated mucositis assessment scales for use in adults. Only three of these scales have received limited evaluation for use in the paediatric population. The unique challenges presented by the paediatric population are excluded from much of the discussion in the literature. CONCLUSION: The paper demonstrates the need to consider the issues specific to children. It must be determined whether previously developed tools are ideally suited for children enrolled on mucositis clinical trials. PMID- 17724622 TI - [Wegener's granulomatosis in ENT: clinical presentation, diagnosis and therapy]. AB - INTRODUCTION: Wegener's granulomatosis (WG) is a vasculitis that effects the upper and lower part of the respiratory tract and the kidneys. Untreated the disease results in death within weeks or months. The diagnosis is based on clinical criteria, level of antineutrophil cytoplasmatic antibodies (ANCA) and signs of granulomatous necrotizing vasculitis in histology. METHODS: A case of an 18-year-old woman with initially symptoms of bilateral "mastoiditis" and weakness of her facial nerve is described. In this case ANCA levels remained normal for 3 months and persistent otological symptoms were predominant. The further clinical course was characterized by neurological problems (Palsy Nn. VII, IX, XII and thrombosis of the right sigmoid sinus). The initial therapy consisted of Prednisone 100 mg and Cyclophosphamide 100 mg daily. The patient has been treated successfully with Methotrexate 20 mg 1 x/week and Prednisone 15 mg/die for 4 months now. CONCLUSION: A common clinical presentation of WG involves the upper respiratory tract. Therefore ENT-specialists should be familiar with the disease. Especially in cases of persistent signs of bilateral "Mastoiditis" and neurological symptoms WG should be ruled out as differential diagnosis. A close interdisciplinary cooperation is essential for therapy and follow-up, because systemic involvement is the limiting prognostic factor. PMID- 17724621 TI - Conducting routine fatigue assessments for use in clinical oncology practice: patient and provider perspectives. AB - GOALS OF WORK: Fatigue is the most common symptom associated with cancer and its treatment. The present study measured patient and provider perceptions of the feasibility and acceptability of conducting computerized fatigue assessments during routine follow-up outpatient clinic visits. MATERIALS AND METHODS: A subset of 64 patients from a larger study, testing items for inclusion in a fatigue item bank, completed two computerized fatigue assessments at 2- to 3 month intervals. After the second assessment, patients completed a questionnaire about the usefulness of the assessments and the understandability of graphic reports depicting the fatigue scores. They were also asked about the optimal frequency for conducting fatigue assessments. Providers were asked similar feasibility questions. MAIN RESULTS: Providers thought displays of fatigue scores would be more useful than patients did. Patients and providers also differed on the frequency with which fatigue assessments should be conducted. Interestingly, of the 37% of patients who reported that assessments should be conducted at a different frequency than the choices that were offered, 50% reported that the assessments should be conducted according to their treatment schedule. The majority of providers thought fatigue assessments should be administered at each MD visit. CONCLUSION: Patients and providers differed about the perceived usefulness of displaying fatigue scores and the frequency with which routine assessments should be conducted. However, both patients and providers appeared to endorse the notion that routine assessments would be beneficial. Integration of routine assessments of commonly experienced symptoms such as fatigue may have important implications for improving symptom management in the future, ultimately resulting in better overall patient care. PMID- 17724623 TI - [Long-term results following mastoid obliteration in canal wall down tympanomastoidectomy]. AB - BACKGROUND: The primary goal in chronic otitis media is the creation of a dry, safe ear with hearing preservation and reconstruction. This study was designed to evaluate the authors' experience using autologous bone pate and conchal cartilage for mastoid obliteration in canal wall down tympanomastoidectomy. METHODS: A retrospective long-term review in 2003 of thirty-nine ears was performed, which underwent mastoid obliteration in canal wall down tympanomastoidectomy between 1993 and 2002 performed by the senior author. Data included questionnaire results, clinical observation as well as pre- and postoperative audiometry. RESULTS: Long-term follow-up shows, that 38 out of 39 ears maintained a small, dry, healthy mastoid cavity. Recurrent cholesteatoma occurred in a single patient. A self-cleaning mastoid bowl was achieved in 90 %, resulting in reduced follow-up visits. Postoperative vertigo in canal wall down revision surgery is clearly diminished due to the mastoid obliteration. Overall, 92 % of patients are satisfied with the surgical result. CONCLUSION: Obliteration of a canal wall down mastoid cavity by autologous bone pate and conchal cartilage is a reliable and effective technique that results in a dry, trouble free mastoid cavity in 90 % of the patients with chronic otitis media. PMID- 17724625 TI - [Liver surgery]. PMID- 17724624 TI - [Knee joint injuries in children]. PMID- 17724626 TI - [Liver function test to predict hepatic failure after liver resection--expensive and without clinical relevance?]. AB - Hepatic failure after liver resection is a complication that is dreaded by surgeons and has a poor outcome. Inadequate functional reserve of the remaining liver parenchyma leads to the inability to regenerate and finally to the progression of liver failure. In order to predict the functional reserve of the remaining liver parenchyma, many different liver function tests have been established. Basis for most liver function assessments are metabolic liver functions such as cytochrome p450 dependent pathways or the extraction and biliary excretion of dye. Nuclear imaging of the liver parenchyma does not only allow visualisation of the liver but also accumulation of information on hepatocyte volume that might be a better predictor for the hepatic reserve and the regenerative capacity compared to the liver volume alone. However, to date no single method has been proven to be able to predict safe limits of resectability. If an underlying liver disease is excluded the resectability is mostly limited by volumetric analysis and technical feasibility of liver resection. In patients with underlying liver disease cirrhosis should be excluded. In case of liver cirrhosis, only Child-Pugh-Turcott A patients with normal bilirubin levels and without portal hypertension should be considered for liver resection. PMID- 17724627 TI - [Liver surgery: what is feasible?]. AB - BACKGROUND: Bilobar hepatic metastases, a small residual liver volume, de-novo and recurrent lesions, simultaneous pulmonary metastases and infiltration of vascular structures are often limiting factors in the surgical treatment of primary and secondary liver tumors. Nevertheless surgery is the "gold standard" with the chance of long-term survival, not possible to achieve with locally ablation and chemotherapy. METHODS: The combination with neoadjuvant chemotherapy and radiofrequency ablation, extended liver resection after selective portal vein embolization, two-stage hepatectomy, resection and reconstruction of vascular structures in deep hypothermia and simultaneous resection of pulmonary metastases, increase the resectability even in patients with poor prognosis achieving 5-year-survival rates between 26-46 % in colorectal liver metastases, 40 % in primary liver tumors and a median survival of 42 months after resection of liver and lung metastases. CONCLUSION: Interdisciplinary treatment and aggressive surgical resection seem to be justified, when performed safely as a curative option. PMID- 17724629 TI - [Liver metastases of colorectal carcinoma--may the DRG-system influence the operative procedure?]. AB - The economic analysis of surgery in colorectal liver metastases reveals the different effectiveness of various follow-up programmes after curative surgery for colorectal cancer. Interval hepatic resection for synchronous liver metastases is recommended in the majority of cases with rectal cancer. This procedure provides benefits for the patient and the hospital under the economic point of view. The interval between primary tumor resection and surgery of liver metastases does not deteriorate the prognosis, on the contrary, unnecessary resections will be avoided if additional metastases will grow in the time between, excluding curative treatment (selection mechanism). The identical statement cannot be applied to patients with colon cancer, since the operative risk is only slightly increased in case of easily accessible liver metastases which may be removed simultaneously. However, also in these patients interval hepatic resection after neoadjuvant chemotherapy should be considered as a therapeutic option! In patients with multiple liver metastases liver surgery as well as radiofrequency ablation or a combination of both may be economically justified. Radiofrequency ablation is the preferred palliative procedure under aspects of cost-effectiveness, however, wether this procedure is superior to chemotherapy alone has not be evaluated so far in prospectively randomized trials. PMID- 17724628 TI - [Liver metastases of colorectal carcinoma--how often can be operated upon?]. AB - Recurrent liver metastases of colorectal carcinoma are frequent. The repeat hepatectomy is superior to other therapeutic options. In about 20% of patients with recurrent liver metastases a complete resection (R0) is possible. The morbidity of repeat hepatectomy is similar to that of first hepatectomy. The 5 year survival rate after repeat hepatectomy ranges between 30 and 40%. Often in the follow-up additional operations become necessary for extrahepatic recurrencies. For determination of the optimal therapy an interdisciplinary approach must be chosen. PMID- 17724630 TI - [Percutaneous, laparoscopic and open surgical radiofrequency ablation of malignant liver lesions]. AB - The growing clinical impact of radiofrequency ablation of liver lesions is reflected by a rapidly increasing number of published papers. Experimental work focuses on factors that reduce the variability of the ablation zone. The Pringle maneuver plays a key role in this question from a surgeon's perspective. Large single center studies and a meta-analysis show a sharp rise in the rate of local recurrences for tumors larger 3 cm. An open surgical approach is significantly correlated to a low local recurrence rate. Bile duct lesions and intrahepatic abscesses are the most frequent complications. Intraductal bile duct cooling can prevent these complications. Three prospective randomized trials support the use of RFA for small hepatocellular carcinoma. The use of RFA in patients with multiple colorectal metastases is supported by single center studies showing a 3 year survival of > 35%. The favourable cost / benefit ratio will make RFA a part of future multimodal cancer therapy concepts. PMID- 17724632 TI - [Hepatocellular carcinoma and cholangiocarcinoma--different prognosis, pathogenesis and therapy]. AB - Primary liver cancer is one of the most common cancer worldwide. Beside hepatocellular carcinoma (HCC), accounting for more than 80%, cholangiocarcinoma (CC) is the second most frequent primary malignant epithelial liver tumor. Combined hepatocellular-cholangiocarcinoma (HCC/CC) is a rare form of liver cancer with a frequency of 1%. Both, hepatocellular carcinoma and cholangiocarcinoma, show a wide geographical variation with low-incidence areas in North America and Europe and high incidence areas in Africa and Asia. Whereas hepatocellular carcinomas develop by malignant transformation of hepatocytes, cholangiocarcinomas arise from the small intrahepatic bile duct epithelium. The UICC-TNM classification of malignant liver tumors is applied for both tumor entities. 70-80% of hepatocellular carcinoma occur in cirrhotic liver. In high incidence areas, such as Asia and Africa, HCC is strongly associated with chronic viral hepatitis B and C and liver cirrhosis. Nutritional factors, toxins and metabolic diseases contribute also to hepatocarcinogenesis. The etiology of cholangiocarcinoma remains unclear, most occur in absence of known etiological factors. But several risk factors including hepatolithiasis, liver fluke infection, and anatomical abnormalities associated with inflammation of the biliary tract have been described. PMID- 17724634 TI - [Case report: primary hyperfractionated accelerated radiotherapy in a case of hepatocellular carcinoma (HCC)]. AB - BACKGROUND: Hepatocellular carcinomas are among the most frequent solid tumour entities worldwide. Because of the advanced tumour stage frequently observed at diagnosis a tumour resection as a curative treatment option is often impossible. Therefore the consideration of alternative treatment methods (possibly enhancing the chance of a subsequent tumour resection) and the improvement of existing palliative treatment options are gaining considerable importance. CASE REPORT: A 77-years-old female patient was diagnosed to have a rapidly progredient expansion in the liver in August 2003. Due to its large extension a local tumour resection was impossible and therefore a hyperfractionated accelerated radiotherapy up to a total dose of 55.0 Gy (single dose 1.2 Gy / 1.3 Gy 2 daily fractions, 12 fractions per week, overall treatment time: 27 days) was applied to both well definable expansions (segments IV and V) from September to October 2003. RESULTS: Despite the large target volume (about 50% of the total liver volume) at an extended HCC and considering the fact that initially symptomatic treatment was aimed at, a curative tumour resectability with subsequent R0 partial liver resection at an interval of 9 months could be achieved by means of radiotherapy treatment. PMID- 17724633 TI - [Transarterial chemoembolization (TACE) of the hepatocellular carcinoma (HCC) in patients with portal vein thrombosis--experiences]. AB - PURPOSE: Comparative analysis of the course of disease in patients with initial diagnosis of portal vein thrombosis in HCC treated with sequential TACE. Evaluation of the efficacy and safety of the method in a selected patient cohort. PATIENTS AND METHODS: The study included 22 patients with HCC that were palliatively treated at least 3 times with TACE. All patients presented a portal vein thrombosis in the initial CT investigation. The TACE-procedure was carried out in regular intervals using a suspension consisting of a fixed dosage of Mitomycin C (10 mg) and 10-20 ml Lipiodol. Follow-up investigations were carried out with contrast enhanced Multislice-CT before and after TACE and control of the laboratory panel (i. e. blood count, liver enzymes and coagulation). RESULTS: Mean survival was 15.7 months (95%-CI 11.6-19.8) with a mean follow-up after last TACE of 6.1 +/- 4.8 months. The mean number of TACE procedures was 5.5 +/- 2.7. During the investigation period 17 / 22 (77.3%) patients died. In 23.5% retrospective analysis revealed a liver decompensation as the cause of death and in 58.8% patients died from the tumor disease. The cumulative 1-, 2- and 3-year survival was 55.0, 21.0 and 0%. The mean tumor size was 7.2 +/- 3.4 cm. Unifocal tumors were found in 18.2% of the cases whereas multifocal tumors were found in 81.8%. In 59.1% of the patients tumor extended to both liver lobes. In case of tumor infiltration of the portal vein survival was significantly worse compared to patients with no evidence of a tumor thrombosis (p = 0.01; cumulative 1- and 2 year survival 46% and 8% vs. 77% and 46%). CONCLUSION: The palliative treatment of the HCC with TACE shows an improvement of survival. There was no increase of death due to liver decompensation in our cohort. Patients with a tumor infiltration of the portal vein showed a significantly worsened survival. The presence of a portal vein thrombosis at the initial diagnosis of the HCC is not an absolute contraindication for TACE treatment but patients have to be elected carefully with critical regard to their liver function. PMID- 17724635 TI - [The hepatocellular carcinoma: alternative therapeutical strategies]. AB - Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world. The prognosis of HCC patients is generally very poor with a 5 year survival rate of less than 5%. Therapeutic strategies include surgery (resection or liver transplantation) and non-surgical interventions, such as percutaneous ethanol injection or radiofrequency thermal ablation as well as transarterial embolization or chemoembolization. Therefore, the development and evaluation of novel HCC treatment strategies such as the use of antiangiogenic, antiproliferative or antiinflammatoric drugs, immune therapeuticals, gene therapy and internal or external radiation are of utmost importance. This review should give an overview of possible alternative therapies in HCC treatment. PMID- 17724636 TI - [Surgical therapy of proximal extrahepatic bile duct tumors (Klatskin tumors)]. AB - Due to their anatomical position, the tendency of early infiltrative growth and their poor prognosis without treatment, klatskin tumors are challenging concerning diagnosis and therapy. In contrast to other tumors of the gastrointestinal tract, for which exact diagnostic and stage dependent therapeutic guidelines could be formulated, clear recommendations for klatskin tumors are missing. Thus, survival rates after local resection, e. g. resection of the bile duct bifurcation alone, show high rates of R1/2 resection and early tumor recurrence. With an additional hepatic resection formally curative resections and long-term survival can be improved. Extended liver resections including the portal vein provide the highest rates of R0 resections for hilar carcinomas of the extrahepatic bile duct. Survival rates after liver transplantation for klatskin tumors are not yet convincing. Promising first results have been reported for the combination of neoadjuvant treatment and liver transplantation and might show future perspectives for the treatment of klatskin tumors. PMID- 17724637 TI - [Palliative locoregional therapy for hilar cholangiocarcinoma: photodynamic therapy and brachytherapy]. AB - In hilar cholangiocarcinoma, only 20-30% of the patients are candidates for curative surgical resection, leaving the majority with merely palliative treatment options. Since the natural history of hilar cholangiocarcinoma is dominated by local complications rather than metastatic disease, local palliative treatment seems a reasonable option. Here, endoluminal photodynamic therapy has emerged as a promising treatment with several prospective observational studies and 2 prospective randomised studies published which included nearly 200 patients. With low complication rate and morbidity, PDT achieves an increased median survival as well as an increased quality of life even in patients with reduced performance status. Radiotherapy is an alternative local treatment option applied as brachytherapy, external beam radiotherapy or combined modality treatment. To date, however, sufficient data from controlled clinical trials are lacking, thus palliative radiotherapy has to be considered an experimental treatment option. PMID- 17724638 TI - ["Fast-track" and elective, laparoscopic colo-rectal surgery]. AB - The aim of this prospective clinical evaluation was to investigate the influence of "Fast-track"-treatment in patients undergoing laparoscopic colorectal operations and its effect on morbidity, hospital stay and recovery. PATIENTS AND METHODS: Bowel cleaning under enteral hypercaloric nutrition (Biosorb Energie, Fa. Nutricia, Germany) was achieved with Fleet (Ferring Arzneimittel, Germany) one day prior to surgery. A peridural catheter was placed preoperatively. Intraoperative electrolyte substitution should not exceed 12 ml/kg KG/h. In case of decreasing intraoperative blood pressure hydroxyethylstarch 6% was substituted. The nasogastric tube was removed immediately after the operation, the urinary catheter was removed on the first postoperative day. The patients stayed on the intermediate care department for one night and started already there with oral feeding and mobilisation (for 2 h). The following days mobilisation increased to 4 h daily under normal enteral nutrition without infusions. RESULTS: Between June 2003 and January 2006, 147 patients undergoing elective colorectal surgery were included in this study. Diverticulitis (n = 114), malignant tumors of the sigmoid colon (n = 6) or rectal cancer (n = 13), colonic adenomas (n = 5), stenotic Crohn's disease (n = 4) and small bowel carcinoid (n = 1), rectal prolaps (n = 1) and elongated colon sigmoideum (n = 4) were indications for surgical treatment. Laparoscopic sigmoid resection (n = 117), left hemicolectomy (n = 11), ileocecal resection (n = 8), anterior resection with total mesorectal excision (n = 9), abdomino-perineal exstirpation (n = 1) and anterior-segmental resection of the rectum (n = 1) were performed. Drainages were removed on the 2nd, peridural catheter on the 3rd postoperative day. Defecation occurred in all patients until the 2 (nd) postop. day. Early postoperative complication rate was 15% (22/147 patients) without mortality. 8 patients (5%) with anastomotic leakage were reoperated. The mean hospital stay was 6 days. The re-admission rate was 3% (4/147 patients) and included one patient with anastomotic leakage. CONCLUSION: "Fast-track"-treatment in combination with minimal-invasive surgery is a safe and comfortable perioperative treatment for patients with elective colorectal operations. PMID- 17724640 TI - [Surgical options in the treatment of rectal prolapse: indications, techniques and results]. AB - Two different approaches can be distinguished in the surgical treatment of rectal prolapse, i. e. the transabdominal route and the perineal procedures. The following article deals with both operative options with a detailed discussion of the Delorme's operation and the perineal rectosigmoidectomy, also known as the Altemeier procedure for the perineal techniques. Regarding abdominal operations simple rectopexy is compared with operations including bowel resection including minimally invasive approaches. In general, perineal procedures for full-thickness rectal prolapse cause less morbidity compared with abdominal operations. They are especially indicated in the elderly and /or high-risk patients. Recurrences, on the other hand, are usually encountered more often following local techniques as compared with abdominal operations. It can be concluded that perineal as well as abdominal procedures remain important options in the surgical treatment of rectal prolapse and should be part of the armamentarium of colorectal surgeons. PMID- 17724641 TI - [Obtaining of mesenchymal progenitor cells from the human umbilical cord]. AB - BACKGROUND: Mesenchymal progenitor cells (MPCs or mesenchymal stem cells, MSC) have the capability for differentiation into various lineages of mesenchymal tissue. MPCs are widely distributed in a variety of tissues in the adult human body and also present in the fetal environment. However, MPCs are a rare population in these tissues. In this study we evaluated the possibility that MPCs or cells with MPC-like potency are present in the umbilical cord (UC). METHODS: Term UCs were collected and stored in sterile saline solution. The UCs (10 cm) were cut into 1 cm length, the vessels were striped manually and the tissue immersed in an enzyme cocktail for 3 h at 37 degrees C. The isolated umbilical cord mesenchymal progenitor cells (UCMPCs) were pelleted by low speed centrifugation, suspended and cultured. RESULTS: (1) Umbilical cord mesenchymal progenitor cells (UMPCs) could be isolated in sufficient quantities and (2) could be cultured easily. (3) These cells demonstrated a fibroblast-like phenotype. (4) They could be expanded in culture and induced to form several different types of cells. (5) In immunochemistry these cells express mesenchymal markers (CD 13, CD 105) but not haematopoetic lineage markers (CD 14 and CD 34). CONCLUSION: Our observation suggested that MPCs are present in human umbilical cord. Instead, it should be considered a valuable resource for the isolation of potent cells for cell-based therapies, especially in general and pediatric surgery. PMID- 17724642 TI - [Gunshot injuries--incidence and treatment]. AB - BACKGROUND: Gunshot injuries are very rare in the European Union. To show the requirements for the trauma surgeon to deal with gunshot injuries this analysis was performed. METHODS: Gunshot injuries seen at Lorenz Boehler Trauma Center from 1997 to 2004 were reviewed. The case histories of 67 patients were analysed for the cause of the gunshot injury, type of weapon, surgical intervention, days of treatment and outcome. RESULTS: The most commonly cause of gunshot injuries were criminal offenses (n = 35). Handguns were used most often (n = 32). The locations of injuries were evenly distributed over head (n = 18 ), trunk (n = 16), upper (n = 15) and lower limb (n = 18). Surgical treatment was performed in 57 patients. The median stay on ICU was 10 days. 6 patients died. CONCLUSION: Gunshot injuries are frequently not confined to the extremities. The challenge for the trauma surgeon is to deal with injuries of the head, chest and abdomen. PMID- 17724643 TI - Replantation of thumb avulsion injuries. AB - PURPOSE: To point out detailed technical considerations and tactical modifications within the experience of 59 replantations of thumb avulsion injuries, to clarify the indications of replantation, and to evaluate the long term results. PATIENTS AND METHODS: Seventy-two thumb avulsions of 510 thumb amputations were treated at our centre between 1986 - 2002. Sixty-two of them were male and 10 were female. The average age of the patients was 27 years. Fifty nine avulsed thumbs were replanted, and 13 were considered as "not replantable" and operated using other reconstructive procedures. Since the main goal of thumb replantation is survival with sensitivity and good function, all the injured tissues were repaired or primarily reconstructed. As a main principle, we always aimed for a one-stage reconstruction including vein grafts for the arterial injury, direct vein repair or vein transfer to establish venous outflow, tendon transfers to restore movement, and nerve transfer to restore sensation. RESULTS: Overall survival rate was 84.7 %. The average follow-up time was 65.2 months. 80 percent of the patients returned to their original work within an average of 4 months after replantation. The patients were generally satisfied with the outcome and ability to use their thumb. The average range of movement of the interphalangeal joint was 75 % of the normal side. On average, key pinch strength was 65 % of contralateral hand. Two-point discrimination was less than 10 mm in 60 % of the cases. Semmes-Weinstein monofilament testing evaluation showed 2.83 in 35 patients, 3.61 in 20, and 6.68 in 4 patients. CONCLUSIONS: In replantation of avulsion amputation of the thumb, functional success depends on repair or reconstruction of all damaged tissues, if necessary, using nerve transfers and tendon transfers. If these could be done primarily as a one-stage reconstruction, the costs would be less, the patients would return to their work when the one stage treatment and rehabilitation is finished, and would also eliminate the technical difficulties encountered in secondary reconstructions. PMID- 17724644 TI - [BIAX total wrist arthroplasty: management and results after 42 patients]. AB - The BIAX total wrist arthroplasty was introduced in 1983 by Cooney, Beckenbaugh and Linscheid in the USA. However the production of this prosthesis was discontinued in 2004 without having developed a follow-up model. Between 2001 and 2003 we have implanted the BIAX prosthesis in 42 cases. In contrast to other studies, our patients had more post-traumatic (n = 19) and degenerative athroses (n = 20), only 3 patients had rheumatoid arthritis of the wrist. Follow-up time was 2.6 (+/- 0.8) years. The patients were 53 (+/- 11) years old. Indication for total wrist arthroplasty was comparable to that for arthrodesis. However, as pain reduction is lower in heavy workers these patients were excluded from arthroplasty implantation. Range of movement was preserved by total arthroplasty or slightly improved. Pain was reduced by 4.5 (+/- 2.3) points from 7.6 (+/- 1.0) to 3.0 (+/- 2.1) using a visual analogue scale with 0 points for no pain and 10 points for severe pain. Patient satisfaction with the operation was 7.7 (+/- 2.2, 1 bad, 10 excellent). 4 patients had a postoperative dislocation. After reposition the joints were permanently stable. In one case a flexion contracture of unknown origin was treated by tendon transfer. In 11 patients the prosthesis had to be removed after 2 (+/- 0.9) years. Four of these patients received an arthrodesis, 7 had a change to the Universal2 prosthesis. The reason for explantation was mainly abrasion of the dorsal polyethylene edge of the proximal socket, resulting in foreign body reaction, synovialitis and loosening of the prostheses in 7 patients and permanent dislocation in 2 patients due to the then flattened socket. These complications led us to abandon the implantation of the BIAX prostheses. PMID- 17724645 TI - [Vascularized joint transfer for finger joint reconstruction]. AB - In a retrospective clinical study 16 vascularized joint transfers to the hand with an average follow-up of 8.2 (3 - 15) years were evaluated. The finger joint defect was caused by trauma in 12 patients, tumour in 2 patients and infection and congenital deformity in 1 patient each. There were 14 men and 2 women. The mean age range was 26 (2 - 42) years. In 6 cases a partial vascularized joint transfer was carried out, with the transplant being harvested in two cases from non-replantable finger according to the "tissue bank concept" according to Chase and in the other two cases from the PIP-joint of the second toe. In 10 patients a complete vascularized joint transfer was carried out, with the joint being harvested from the hand in 6 cases and from the 2nd toe in 4 cases. The following criteria were evaluated: active range of motion (neutral-0-method), postoperative arthritis, growth and complications. Active range of motion of the transplanted joint was for partial PIP-joint transfer Ex/Flex 0/20/65 degrees und for partial MP-joint transfer 0/20/30 degrees . After DIP-to-PIP-joint transposition active range of motion was measured Ex/Flex 0/20/60 degrees , after PIP-to-PIP transposition 0/30/60 degrees , PIP-to-MP-transposition 0/20/80 degrees and after MP-to-MP-transposition 0/20/57 degrees . The results after microvascular PIP joint transfer from the 2nd toe for PIP-joint reconstruction were 0/25/58 degrees for PIP-joint reconstruction and 0/15/70 degrees for MP-joint reconstruction. Arthritic changes could be seen in 3 out of 4 patients with partial vascularized joint transfer. In all complete joint transfers there was no clinical and radiological evidence of arthritis even after 15 years. In the two skeletal immature patients at the time of transfer, normal growth compared to the contralateral donor site could be seen. In 8 out of 14 patients complications occurred. In 4 cases tendolysis of the extensor tendon was necessary. In 4 patients skeletal malalignment (3 x sagittal plane, 1 x rotation) was diagnosed. In one patient flexor pulley reconstruction was necessary in order to correct a bowstring deformity. Indications for vascularized joint transfer at the finger in children is set because of lack of therapy option offering normal growth potential. In adults vascularized joint transfer is indicated in case of contraindication for prosthetic joint replacement or arthrodesis. PMID- 17724646 TI - [DIGITOS-prosthesis for the proximal interphalangeal joint--long-term results]. AB - Most important methods for the surgical treatment of painful arthritis of the proximal interphalangeal joint are the joint fusion or the implantation of a prosthesis. There are a lot of different models for joint replacement. Sixteen patients received 19 middle joint replacements performed with the DIGITOS prosthesis between 1996 and 1999. Over a period of seven years, 14 patients with 17 prostheses have been observed prospectively. In the 7-year follow-up, a minimal radiolucent line at the bone-cement junction and huge periarticular osteophytes could be found in every case. No cortical penetration, luxation, or implant fractures were recorded. The preoperative median range of motion was 50 degrees. Postoperatively, there was an improvement to 60 degrees. The range of motion decreased to 50 degrees after one year and to as little as 30 degrees after seven years. Preoperatively, eleven patients had pain with activity and three had pain without activity. During the whole follow-up period there were only two patients who had pain at work. All patients were satisfied with the results of the operation throughout the control period and would choose the same treatment again. PMID- 17724647 TI - [Post-acute management of fractures of the proximal interphalangeal joint with metal prosthesis: first experience]. AB - AIM: The purpose of this report is to present our management strategy for fractures of the proximal interphalangeal joint by means of a metal prosthesis via a dorsomedial approach and to discuss our clinical and radiological results. PATIENTS AND METHODS: Two patients with complex crush injuries and fractures of the proximal interphalangeal joints who were treated surgically in the years 2004 and 2005 were examined again at an average of 13 months postoperatively. Management was standardised, first in the emergency room with wound cleaning and temporary osteosynthesis. About 3-4 weeks later a secondary procedure with implantation of a metallic prosthesis was carried out. Clinical and radiological follow-ups were performed. The final result was evaluated by means of the modified Mayo wrist score. In addition, the patients' functional limitations were assessed quantitatively with the DASH evaluation scheme. RESULTS: In one of the two patients, revision surgery in the form of a definitive arthrodesis was necessary. Grip strength on the injured side was weakened by 10 %. One patient achieved a very good and the other a good result upon evaluation with the modified Mayo wrist score. The DASH evaluation gave on average a functional limitation of 30 points. PMID- 17724648 TI - [Suspension arthroplasty of the thumb carpometacarpal joint in different views--a questionnaire]. AB - PURPOSE: Obviously there are different judgements of the results of suspension arthroplasties of the thumb carpometacarpal joint. Consequently, the three main groups involved in therapy were asked about this topic. PATIENTS AND METHODS: 51 patients who had had a suspension arthroplasty on the thumb carpometacarpal joint in the period 1998 - 2006 were questioned. 12 of these patients were operated on both hands (63 operations). A questionnaire sent to 250 family doctors was compared with the results from the 51 patients. Furthermore there was an interview by telephone which included 25 practising specialists (orthopaedicians and surgeons). RESULTS: The results contrasted widely. Concerning the operation, 50 from 51 patients had a high subjective satisfaction. The family doctors had a different view. Nearly 80 % disregarded the success of the operation or they could not judge the chances. Only 50 % of all family doctors arranged for an X ray or a consultation at a specialist when the patient had continuing problems. The results of the 25 specialists were also not uniform. 50 % of them, especially the hand surgeons, believe in the success of the primary osteoarthritis operation. The high barrier to operations for rhizarthrosis is based on a lack of information. PMID- 17724649 TI - [Carpo-metacarpal flexion of the thumb in healthy adults]. AB - Metacarpophalangeal flexion of the thumb is known to be highly variable. To obtain normative values, active metacarpophalangeal flexion of the thumb was measured bilaterally in healthy Caucasian adults (female n = 403; male n = 366) in a standardized manner. Independent of gender, inter-individual variation was high, ranging between 16 degrees and 90 degrees and showing a continuous decrease with increasing age. Women showed a bigger range of motion than men but in both range of motion was higher on the left thumb (mean 1.4 degrees in women and mean 1.1 degrees in men). No influence of hand dominance was observed. Thus, the healthy contralateral side should be used as parameter of comparison. PMID- 17724650 TI - [Diagnosis and therapy of carpal tunnel syndrome--guideline of the German Societies of Handsurgery, Neurosurgery, Neurology, Orthopaedics, Clinical Neurophysiology and Functional Imaging, Plastic, Reconstructive and Aesthetic Surgery, and Surgery for Traumatology]. AB - Evidence-based supradisciplinary guideline that deals with the epidemiology, pathogenesis, symptoms, clinical and electrophysiological diagnosis, supplementary imaging investigations, differential diagnosis, conservative and surgical treatments, prognosis and course along with complications and revision surgery. The recommendations on investigation and treatment are based on a comprehensive literature search with critical evaluation and two consensus methods (expert group and Delphi technique) within the participating specialist societies. Besides this long version, a short version and a patient version can be viewed through the AWMF platform. The development of the guideline and the methodological foundations are documented in a method report. MAIN STATEMENTS: Apart from an accurate history and clinical neurological examination (including clinical tests), electrophysiological investigations (distal motor latency and sensory neurography) are particularly important. Radiography, MRI, high resolution ultrasonography can be regarded as optional supplementary investigations. Among conservative treatment methods, treatment with a nocturnal splint and local infiltration of a corticosteroid preparation are effective. Oral steroids, splinting and ultrasound showed only short-term benefit. Surgical treatment is clearly superior to all other methods. Open and endoscopic procedures (when the endoscopic surgeon has sufficient experience) are equivalent. A routine epineurotomy and interfascicular neurolysis cannot be recommended. Early functional treatment postoperatively is important. PMID- 17724651 TI - [Development and implementation of the guideline "Diagnosis of and Therapy for Carpal Tunnel Syndrome"]. AB - In the period from July 2005 through November 2006, the evidence-based guidelines were developed by a steering committee consisting of three members from each of the societies involved (German Society for Hand Surgery, German Society of Neurosurgery, German Society of Neurology and German Society of Orthopaedics), coordinated by one member each from the DGH and the DGNC, under the methodological guidance of Prof. Selbmann of the German Association of the Scientific Medical Societies (AWMF). Six all-day working sessions and one proceeding to build a consensus (modified Delphi process) were held within the seven specialised societies involved. Degrees of recommendation, based upon the degree of evidence of the underlying literature studies, modified, if necessary, by the expert opinion of the steering committee's members and the external evaluators of the Delphi round, were established for the most important diagnostic and therapeutic methods. In addition to the long version, a short version and a patient information bulletin were prepared as well, and the ways, means, and considerations surrounding their realisation and implementation, and other potential developments were also pursued. PMID- 17724652 TI - [Reintervention after endoscopic surgery of the carpal tunnel syndrome]. AB - BACKGROUND: The carpal tunnel syndrome is one of the most frequent peripheric nerve compression syndromes. Almost 15 years ago, the endoscopic surgery of the carpal tunnel was introduced, in order to reduce postoperative pain and to shorten the length of the postoperative inactivity period, especially work absence. In the literature the rate of complications due to the endoscopic carpal tunnel release surgery is reported differently in respect to number and severity. This paper summarizes all reinterventions after endoscopic surgery in a single specialized hand surgery department, which prefers the open approach even for first time interventions. PATIENTS AND METHOD: A retrospective analysis of all reoperations between 1998 and 2006 is presented. There were 22 reinterventions done on 21 patients. A reoperation was performed if the symptoms of the carpal tunnel syndrome persisted or new pain or sensomotor deficit appeared. There were 8 male and 14 female patients. The age span ranged from 28 to 86 years. The time distance between the first and the second surgery was between 19 days and 36 months. RESULTS: Most of the intraoperative findings were incomplete releases of the retinaculum (n = 13). In three cases abundant adherences caused the clinical symptoms. Three times pathologies were found in carpal tunnel, which could not be recognized or treated endoscopically: severe bleeding in the synovia, massive synovialitis and a swannoma of the median nerve. In seven patients transsected nerves had to be treated: one complete transsection of the median nerve, two nerves with injured radial fascicles, two nerves with violated ulnar fascicles, one neuroma of the median nerve and one transsection of both branches of the ulnar nerve. CONCLUSION: In 22 cases the result of the endoscopic release of the carpal tunnel forced to redo the intervention. In seven patients there were important lesions of the neurovascular structures. Since the long-term result of the endoscopic and open surgery of the carpal tunnel is comparable, it should be discussed if endoscopic surgery is justified even with the risk of mutilant complications and which preoperative imaging procedure is required to discover pathologies and anatomical variants. PMID- 17724653 TI - Molecular mechanics (MM3(pi)) conformational analysis of molecules containing conjugated pi-electron fragments: Leucomycin-V. AB - The conformations of the 16-membered macrolide antibiotic leucomycin-V (1) were studied with molecular mechanics. Leucomycin-V contains a conjugated pi-electron fragment and necessitates special treatment with the MM3(pi) modeling protocol. Comparison was made with results from the standard MM3 scheme. The CONFLEX conformational search procedure was used for finding low-energy conformations. The computed data are indicative for the existence of mainly one conformation of the macro-ring of 1 and minor participation of several others. Intramolecular hydrogen bonds play important roles for the preferred geometry of the macro-ring and the conformations of the side chains. The most probable macro-ring conformation of 1 is very similar to the preferred conformation of another 16 ring macrolide antibiotic, tylosin. The same order of conformational preference for 1 was estimated with the MM3 and the MM3(pi) methods. Surprisingly, when changing the chirality of the C(9) macro-ring atom of 1, the two methods produced different order of conformational preferences for the 9-epi form (2), as well as enhanced population of several clusters of conformations. PMID- 17724654 TI - The prediction of the circular dichroism of the benzene chromophore: TDDFT calculations and sector rules. AB - The CD spectra of the series PhCH(Me)R, with R = Et (1), nPr (2), iPr (3), and tBu (4), are reported (1-3 for the first time) at room temperature in the 185-280 nm range and at 183 K. These purely hydrocarbon compounds represent the simplest chiral systems containing the phenyl chromophore and exhibit Cotton effects exclusively allied with the benzene transitions. The bands in 1La and 1Lb regions were checked against the available sector rules, with discordant outcomes. Time dependent density-functional theory calculations, with various functionals and basis sets tested, correctly reproduced the prominent CD bands observed for 1-4. PMID- 17724655 TI - Synthesis and chiroptical properties of a helical poly(phenylacetylene) bearing optically active pyrene pendants. AB - A novel poly(phenylacetylene) derivative bearing optically active pyrene moieties as the pendant groups (poly-(R)-1) was prepared by the polymerization of the corresponding monomer (R)-1 in the presence of a rhodium catalyst, and its chiroptical property was investigated. Poly-(R)-1 exhibited an induced circular dichroism (ICD) in the polymer backbone region due to the predominantly one handed helical conformation. The ICD pattern dramatically changed and was accompanied by inversion of the Cotton effect sign in response to a change in the temperature and solvent, indicating that poly-(R)-1 underwent a helix-helix transition in response to the external stimuli. PMID- 17724656 TI - Mucoadhesive tablet releasing iodine for treating oral infections. AB - Iodine complexes with ethyl cellulose (EC) and hydroxypropyl cellulose (HPC) were prepared by immersing polymer powder in aqueous solutions of iodine. These complexes were incorporated in a mucoadhesive tablet for potential use as antimicrobial agent for treating oral infections. The release profile of iodine from the adhesive tablets was determined and the antimicrobial activity was assessed by diffusion assays using Candida albicans and Porphyromonas gingivalis cultures. Iodine was readily absorbed up to 35%w/w in the polymers. A differential scanning colorimeter (DSC) scan revealed a correlation between the endotherm peak of the complexes and the iodine content in the polymer complex. The tablets exhibited marked antifungal and antibacterial activities against the fungal/bacterial strains tested. PMID- 17724657 TI - Characterization of amorphous solids with weak glass transitions using high ramp rate differential scanning calorimetry. AB - Measurement of the glass transition temperature (T(g)) of proteins and other high molecular weight polymers in the amorphous state is often difficult, since the transition is extremely weak, that is, the DeltaC(p) at the glass transition temperature is small. For example, little is known about the solid-state properties of hydroxyethyl starch (HES), which is beginning to become more commonly evaluated as a bulking agent in pharmaceutical products. For weak thermal events, such as the change in heat capacity at the T(g) of a pure protein or large synthetic polymer, increased heating rate should produce greater sensitivity in terms of heat flow. Recent innovations in rapid scanning technology for differential scanning calorimetry (DSC) allow measurements on materials where the thermal events are difficult to detect by conventional DSC. In the current study, measurements of the T(g) of proteins in the solid state, amorphous pharmaceutical excipients which have small DeltaC(p) at the glass transition temperature, and bacterial spores, have all been made using high ramp rate DSC, providing information on materials that was inaccessible using conventional DSC methods. PMID- 17724658 TI - Biorelevant refinement of the Caco-2 cell culture model to assess efficacy of paracellular permeability enhancers. AB - Epithelial cell monolayers are routinely used to evaluate efficacy of paracellular permeability enhancers (PPEs). The purpose of the present work was to investigate how biorelevant refinements to the Caco-2 cell model impact in vitro efficacy (decrease in transepithelial electrical resistance and increase in mannitol permeability) of PPEs. Standard transport buffer was replaced by fasted state simulated intestinal fluid (FaSSIF) or serum; or stirring was performed to decrease the unstirred water layer thickness. Apical FaSSIF significantly reduced the efficacy of amphiphilic PPEs palmitoylcarnitine and hexadecylphosphocholine and reduced the amount of these PPEs associated with cells. In contrast, FaSSIF did not affect efficacy of nonamphiphilic PPEs, ethylenediaminetetraacetic acid or 3-nitrocoumarin. Basolateral serum increased the transepithelial flux of PPEs, but did not lessen their potency. Stirring increased the flux of all PPEs, and also enhanced the potency of the amphiphilic PPEs. These results show that inclusion of FaSSIF and agitation in the cellular models significantly alter the efficacy of amphiphilic PPEs but not of hydrophilic or lipophilic PPEs. Future studies should be directed at evaluating the ability to these refined in vitro systems to predict in vivo effects of PPEs. PMID- 17724659 TI - Characterization of antigens adsorbed to anionic PLG microparticles by XPS and TOF-SIMS. AB - The chemical composition of the surface of anionic PLG microparticles before and after adsorption of vaccine antigens was measured using X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (TOF-SIMS). The interfacial distributions of components will reflect underlying interactions that govern properties such as adsorption, release, and stability of proteins in microparticle vaccine delivery systems. Poly(lactide-co-glycolide) microparticles were prepared by a w/o/w emulsification method in the presence of the anionic surfactant dioctyl sodium sulfosuccinate (DSS). Ovalbumin, lysozyme, a recombinant HIV envelope glyocoprotein and a Neisseria meningitidis B protein were adsorbed to the PLG microparticles, with XPS and time-of-flight secondary mass used to analyze elemental and molecular distributions of components of the surface of lyophilized products. Protein (antigen) binding to PLG microparticles was measured directly by distinct elemental and molecular spectroscopic signatures consistent with amino acids and excipient species. The surface sensitive composition of proteins also included counter ions that support the importance of electrostatic interactions being crucial in the mechanism of adsorptions. The protein binding capacity was consistent with the available surface area and the interpretation of previous electron and atomic force microscope images strengthened by the quantification possible by XPS and the qualitative identification possible with TOF-SIMS. Protein antigens were detected and quantified on the surface of anionic PLG microparticles with varying degrees of efficiency under different adsorption conditions such as surfactant level, pH, and ionic strength. Observable changes in elemental and molecular composition suggest an efficient electrostatic interaction creating a composite surface layer that mediates antigen binding and release. PMID- 17724660 TI - Rapid throughput solubility screening method for BCS class II drugs in animal GI fluids and simulated human GI fluids using a 96-well format. AB - A rapid solubility-screening assay was developed with a focus on Biopharmaceutic Classification Scheme (BCS) class II drug solubility in animal and simulated human gastrointestinal (GI) fluids. The assay enables biologically promising drug leads to be evaluated for solubility limitations earlier in the drug development process, minimizes GI fluid needs, and produces in vitro solubility information with potential in vivo implications. A number of BCS II drugs were dissolved in DMSO at approximately 40 mM, and robotically distributed to a 96-well plate. The DMSO was evaporated and drugs were equilibrated with selected GI fluids, both fed and fasted states. After equilibration, precipitated wells were subjected to HPLC analysis. A spreadsheet calculated solubility automatically from HPLC output. Intra-day, inter-day, and inter-plate reproducibility were within 15% RSTD for the tested drugs with the primary source of variability being injection precision of our injector system. The reported solubility from screening assays was well correlated with literature data (r(2) = 0.80) with a slope of 0.86 and (r(2) = 0.99) with a slope of 0.89. This screening assay converts conventional solubility measurements to a 96-well format for increased throughput (>12 samples/h), reduces fluid needs, and minimizes drug consumption. PMID- 17724661 TI - A developmental staging series for the lizard genus Anolis: a new system for the integration of evolution, development, and ecology. AB - Vertebrate developmental biologists typically rely on a limited number of model organisms to understand the evolutionary bases of morphological change. Unfortunately, a typical model system for squamates (lizards and snakes) has not yet been developed leaving many fundamental questions about morphological evolution unaddressed. New model systems would ideally include clades, rather than single species, that are amenable to both laboratory studies of development and field-based analyses of ecology and evolution. Combining an understanding of development with an understanding of ecology and evolution within and between closely related species has the potential to create a seamless understanding of how genetic variation underlies ecologically and evolutionarily relevant variation within populations and between species. Here we briefly introduce a new model system for the integration of development, evolution, and ecology, the lizard genus Anolis, a diverse group of lizards whose ecology and evolution is well understood, and whose genome has recently been sequenced. We present a developmental staging series for Anolis lizards that can act as a baseline for later comparative and experimental studies within this genus. PMID- 17724662 TI - The fenton activity of iron(III) in the presence of deferiprone. AB - Hydroxyl radical production from a range of clinically relevant iron chelators in the presence of hydrogen peroxide was measured using the deoxyribose oxidation assay. Hydroxyl radical production from an iron complex is dependent on whether the ligand is able to completely surround the iron, thereby preventing access of reductants to the coordinated iron cation. The partially coordinated [(deferiprone)(2)Fe(III)](+) complex is able to generate hydroxyl radicals in the presence of oxidants, whereas the fully coordinated [(deferiprone)(3)Fe(III)](0) complex is not. Hydroxyl radical production from iron(III)deferiprone complexes is dependent on the molar ratio of iron to deferiprone, which, in turn, affects the speciation of the complex. Mass spectrometry data have confirmed the presence of the [(deferiprone)(2)Fe(III)](+) complex in aqueous solution. Hydroxyl radical production from the [(deferiprone)(2)Fe(III)](+) complex is maximal in the presence of equimolar ascorbate and hydrogen peroxide and is abolished in the absence of hydrogen peroxide. Under biological conditions, any [(deferiprone)(2)Fe(III)](+) complex formed intracellularly will be rapidly reduced by ascorbate. The resulting unstable iron(II) complex will dissociate to hexa-aquo iron(II), a major component of the endogenous intracellular labile iron pool. PMID- 17724663 TI - Metabolism and disposition of resveratrol in the isolated perfused rat liver: role of Mrp2 in the biliary excretion of glucuronides. AB - In this study, the hepatic metabolism and transport system for resveratrol was examined in isolated perfused livers from Wistar and Mrp2-deficient TR(-) rats. Based on extensive metabolism to six glucuronides and sulfates (M1-M6), the hepatic extraction ratio and clearance of resveratrol was very high in Wistar and TR(-) rats (E: 0.998 vs. 0.999; Cl: 34.9 mL/min vs. 36.0 mL/min). However, biliary excretion and efflux of conjugates differs greatly in TR(-) rats. While cumulative biliary excretion of the glucuronides M1, M2, M3, and M5 dropped dramatically to 0-6%, their efflux into perfusate increased by 3.6-, 1.8-, 2.5-, and 1.5-fold. In contrast, biliary secretion of the sulfates M4 and M6 was partially maintained in the Mrp2-deficient rats (61% and 39%) with a concomitant decline of their efflux into perfusate by 33.2% and 78.1%. This indicates that Mrp2 exclusively mediates the biliary excretion of resveratrol glucuronides but only partly that of sulfates. Cumulative secretion of unconjugated resveratrol into bile of TR(-) rats was only reduced by 40%, and into perfusate by 19%, suggesting only a minor role of Mrp2 in resveratrol elimination. In summary, resveratrol was dose-dependently metabolized to several conjugates whereby the canalicular transporter Mrp2 selectively mediated the biliary excretion of glucuronides. PMID- 17724664 TI - Fluoxetine pretreatment effects pharmacokinetics of 3,4 methylenedioxymethamphetamine (MDMA, ECSTASY) in rat. AB - Fluoxetine has been shown to provide protection from MDMA induced long term neurotoxicity. The purpose of this investigation is to evaluate the pharmacokinetic drug interaction between MDMA and fluoxetine and also to determine the role of P-glycoprotein (P-gp) on mediating drug-drug interactions with MDMA. Bi-directional transport studies were conducted across MDCK-MDR1 and Caco-2 monolayers. MDMA brain and plasma levels were measured in P-gp deficient [mdr1a(-/-)] and normal [mdr1a(+/+)] mice after a 5 mg/kg i.p. dose of MDMA. Sprague-Dawley rats were pretreated with fluoxetine (4 days, 10 mg/kg, i.p.) or saline followed by MDMA (10 mg/kg, p.o.) and brain and plasma samples were collected over 10 h. MDMA and its active metabolite MDA were quantified using a HPLC method with fluorescence detection. In transport studies MDMA exhibited high permeability with essentially unpolarized transport. No significant difference in MDMA and MDA brain levels were seen in P-gp deficient versus normal mice. Pretreatment of rats with fluoxetine resulted in an increase in MDMA (1.4-fold) and MDA (1.5-fold) exposure in both brain and plasma. Elimination half-life was increased for MDMA (2.4 vs. 4.9 h) and MDA (1.8 vs. 8.2 h) with fluoxetine pretreatment. P-gp does not play a physiologically relevant role in absorption and distribution of MDMA, hence this transporter may not have a role in drug-drug interactions with MDMA. Fluoxetine pretreatment to provide protection from MDMA induced long term neurotoxicity decreases elimination of MDMA and MDA and may lead to enhanced risk of MDMA acute toxic effects. Overall, our results indicate that caution need to be practiced when recommending fluoxetine as an agent to provide protection from MDMA induced long term neurotoxicity. PMID- 17724665 TI - Temperature scanning FTIR analysis of interactions between sugar and polymer additive in amorphous sugar-polymer mixtures. AB - The impact of a polymer additive (polyvinylpyrrolidone, PVP) on hydrogen bonding in amorphous sugar matrices as well as on the glass transition temperature, T(g), were examined by temperature scanning Fourier transform infrared spectroscopy (TS FTIR). An amorphous sugar matrix containing PVP was prepared by air-drying an aqueous solution of a sugar-PVP mixture. The hydrogen bonds in the sugar-PVP mixture (sugar-PVP and sugar-sugar hydrogen bonds) were analyzed from the IR peak positions corresponding to the stretching vibration of C==O groups of PVP and O- H groups of the sugar and the temperature dependence of the peak position of the O--H stretching vibration band. The addition of PVP to amorphous mono and disaccharides significantly lowered the extent of hydrogen bond formation while interactions between sugars and the PVP tended to prevent the disruption of hydrogen bonds due to increasing temperature, the magnitude of which was larger for larger oligomers. The T(g) value for the amorphous sugar was increased by the addition of PVP in many cases. As the size of sugar molecule became larger, the relative magnitude of the increased T(g) by PVP to the difference between the T(g) values for sugar alone and PVP alone became larger and then reached a certain level; it was slight in the case of glucose. Collectively, these results demonstrate that the magnitude of the impact of PVP on an amorphous sugar matrix strongly vary and are dependent on the types of sugar. PMID- 17724666 TI - Prediction of drug tissue to plasma concentration ratios using a measured volume of distribution in combination with lipophilicity. AB - One of the drug specific parameters needed in physiologically based pharmacokinetic (PBPK) models is the tissue to plasma drug concentration ratios (K(p) values). The aim of this study was to develop an empirical method for predicting K(p) values using a preclinically determined in vivo volume of distribution, in combination with descriptors for drug lipophilicity. Pharmacokinetic data in laboratory animals for a wide range of drug compounds were collected. Obtained correlations between K(p) values for muscle and other tissues, in a training set of 49 compounds, were used to predict K(p) values for a test set of 22 compounds, based on their volume of distribution and lipophilicity. Predicted K(p) values agreed well with experimentally determined values (n = 118), especially for noneliminating tissues (r(2) = 0.81) with 72% and 87% being within a factor +/-2 and +/-3, respectively. In conclusion, we present an empirical method based on a measured volume of distribution and a drug lipophilicity descriptor, which can be used to predict tissue K(p) values with reasonable accuracy. PMID- 17724667 TI - Dilution of microbicide gels with vaginal fluid and semen simulants: effect on rheological properties and coating flow. AB - Microbicides are agents applied topically to the vagina to prevent HIV transmission. Microbicide products formulated as semi-solid dosage forms or "gels" coat vulnerable tissue to deliver active ingredients. Effective microbicide delivery vehicles must have appropriate rheological properties to ensure appropriate deployment in vivo. Microbicide products become diluted by fluids in the vagina after application; dilution affects vehicle rheological properties and mechanics of vaginal distribution, thus affecting efficacy. To simulate the changes that might occur after application, this study analyzed the effects of small dilutions (10-30%) with vaginal fluid and semen simulants on three semi-solid vaginal formulations: a cellulose lubricant (KY Jelly), a polyacrylic acid moisturizer (Replens), and a carrageenan prototype microbicide (Carraguard). Rheological behavior was characterized using cone-and-plate rheometry. Data were fitted to either the power-law, Carreau, or Herschel-Bulkley model. Rheological parameters from these fits were input to models of coating flow due squeezing, and the simulated area coated output from these models was used to compare the responses of the different formulations to the two diluents for varying degrees of dilution. There were differences in the responses of the three materials to dilution. Even small dilutions altered the rank order of vaginal coating rates compared to the undiluted formulations. PMID- 17724668 TI - Drug-polymer interaction and its significance on the physical stability of nifedipine amorphous dispersion in microparticles of an ammonio methacrylate copolymer and ethylcellulose binary blend. AB - Using spectroscopic and thermal analysis, this study investigated drug-polymer interaction and its significance on the physical stability of drug amorphous dispersion in microparticles of an ammonio polymethacrylate copolymer (Eudragit RL) (RL) and ethylcellulose (EC) binary blend (RL/EC = 2:1 w/w) prepared for use in controlled release of poorly water-soluble drugs. Solid dispersion of the model drug, nifedipine in the microparticles could be described as an ideal amorphous mixture for drug loadings up to 11% w/w. The antiplasticizing effect of the polymer blend was indicated by a significant increase in the glass transition point from approximately 50 degrees C for the amorphous nifedipine to approximately 115 degrees C for its solid solution. Moreover, shifts in infrared vibration wavenumber of nifedipine carbonyl and amine groups suggested that the hydrogen bonds (H-bonds) originally formed among nifedipine molecules were broken and replaced by those formed between nifedipine and polymers in the microparticles. Further infrared analysis on nifedipine amorphous dispersions with a single polymer, namely RL or EC, confirmed the proposed hydrogen-bonding interactions; and their stability study results suggested that both antiplasticizing effects and hydrogen bonding of EC and RL with nifedipine might be responsible for the physical stability of the microparticles of nifedipine amorphous dispersion with a RL/EC binary blend. PMID- 17724669 TI - Estimation of ADME properties in drug discovery: predicting Caco-2 cell permeability using atom-based stochastic and non-stochastic linear indices. AB - The in vitro determination of the permeability through cultured Caco-2 cells is the most often-used in vitro model for drug absorption. In this report, we use the largest data set of measured P(Caco-2), consisting of 157 structurally diverse compounds. Linear discriminant analysis (LDA) was used to obtain quantitative models that discriminate higher absorption compounds from those with moderate-poorer absorption. The best LDA model has an accuracy of 90.58% and 84.21% for training and test set. The percentage of good correlation, in the virtual screening of 241 drugs with the reported values of the percentage of human intestinal absorption (HIA), was greater than 81%. In addition, multiple linear regression models were developed to predict Caco-2 permeability with determination coefficients of 0.71 and 0.72. Our method compares favorably with other approaches implemented in the Dragon software, as well as other methods from the international literature. These results suggest that the proposed method is a good tool for studying the oral absorption of drug candidates. PMID- 17724670 TI - Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? AB - The trends in head and neck cancer incidence and smoking prevalence are reviewed, discussing where such trends parallel but also how and why they may not. In the U.S., public health efforts at tobacco control and education have successfully reduced the prevalence of cigarette smoking, resulting in a lower incidence of head and neck cancer. Vigilance at preventing tobacco use and encouraging cessation should continue, and expanded efforts should target particular ethnic and socioeconomic groups. However, an unfortunate stagnation has been observed in oropharyngeal cancer incidence and likely reflects a rising attribution of this disease to oncogenic human papillomavirus, in particular type 16 (HPV-16). For the foreseeable future, this trend in oropharyngeal cancer incidence may continue, but with time the effects of vaccination of the adolescent and young adult female population should result in a lower viral prevalence and hopefully a reduced incidence of oropharyngeal cancer. To hasten the reduction of HPV-16 prevalence in the population, widespread vaccination of adolescent and young adult males should also be considered. PMID- 17724671 TI - Prospective investigation of the cigarette smoking-head and neck cancer association by sex. AB - BACKGROUND: Men are approximately 3 times more likely to develop squamous cancers of the head and neck (oral cavity, pharynx, and larynx) than women. Very few prospective studies have examined the association between cigarette smoking and cancers of the head and neck in women, even though the rates of smoking in women are increasing rapidly worldwide. METHODS: The association between cigarette smoking and head and neck cancer was investigated in 476,211 participants, aged 50-71 years, of the National Institutes of Health/American Association of Retired Persons (NIH-AARP) diet and health study by using age-standardized incidence rates and hazard ratios from Cox models adjusted for other risk factors for these cancers. RESULTS: Over the course of follow-up (1995 through 2000), 584 men and 175 women were diagnosed with head and neck cancer. Nonsmoking (24.4), former smoking (36.9), and current smoking (147.3) men had higher rates of incident head and neck cancer per 100,000 person-years of follow-up than women did in each equivalent category of cigarette use (non: 4.8; former: 17.2; current: 75.7). The hazard ratios associated with smoking were significantly larger in women (12.96; 95% confidence interval [CI], 7.81-21.52) than in men (5.45, 95% CI, 4.22-7.05; P for interaction: <.001) for head and neck cancer overall and also for the 3 subsites (oral cavity, oro-hypopharynx, and larynx) examined in stratified analyses. Ever-smoking accounted for 45% of head and neck cancers in men and 75% in women, assuming causality. CONCLUSIONS: Cigarette smoking is a strong risk factor for head and neck cancer in both men and women. Incidence rates of head and neck cancer were higher in male smokers than female smokers, but smoking may explain a higher proportion of head and neck cancer in women than in men. PMID- 17724672 TI - Behavioral variation and reproductive success of male baboons (Papio anubis x Papio hamadryas) in a hybrid social group. AB - We take advantage of an array of hybrid baboons (Papio anubis x Papio hamadryas) living in the same social group to explore the causes and consequences of different male mating strategies. Male hamadryas hold one-male units and exhibit a sustained, intense interest in adult females, regardless of the latter's reproductive state. Anubis baboons, by contrast, live in multi-male, multi-female groups where males compete for females only when the latter are estrous. These two taxa interbreed to form a hybrid zone in the Awash National Park, Ethiopia, where previous work has suggested that hybrid males have intermediate and ineffective behavior. Here, we first examine male mating strategies with respect to morphological and genetic measures of ancestry. We found significant relationships between behavioral measures and morphology; males with more hamadryas-like morphology had more hamadryas-like behavior. However, genetic ancestry was not related to behavior, and in both cases intermediates displayed a previously unreported level of behavioral variation. Furthermore, male behavior was unrelated to natal group. Second, we evaluated reproductive success by microsatellite-based paternity testing. The highest reproductive success was found for individuals exhibiting intermediate behaviors. Moreover, over nine years, some genetically and morphologically intermediate males had high reproductive success. We conclude that the behavior of hybrid males is therefore unlikely to be an absolute barrier to admixture in the region. PMID- 17724673 TI - Tradeoffs between somatic and gonadal investments during development in the African clawed frog (Xenopus laevis). AB - Tradeoffs between time to and size at metamorphosis occur in many organisms with complex life histories. The ability to accelerate metamorphosis can increase survival to the next life stage, but the resulting smaller size at metamorphosis is often associated with lower post-metamorphic survival or reduced fecundity of adults. Reduced fecundity is thought to be because of reduced energy reserves, longer time to maturity, or reduced capacity to carry eggs or compete for mates. This pattern could also be explained by a shift in allocation to somatic growth that further retards the growth or development of reproductive tissues. The main goal of this study was to determine if the relationship between growth and development of somatic and gonadal tissues depends on environmental conditions. We address this question through two experiments in which we quantify the development and growth of the body and gonads of Xenopus laevis reared in different resource environments. First, tadpoles were reared communally and development and growth were evaluated over time. Restricted food reduced somatic and gonadal growth rate, but did not affect the developmental rate of either tissue type. Second, tadpoles were reared individually and evaluated at metamorphosis. Restricted food reduced somatic development and growth, but only influenced size, and not developmental stage of testes at metamorphosis. This work demonstrates that environmental conditions influence tradeoffs between growth and development of somatic and gonadal tissues, apparently in a sex specific manner. These tradeoffs may contribute to phenotypic correlations between small size and reduced fitness. PMID- 17724674 TI - Calcium-induced quiescence of sperm motility in the bluegill (Lepomis macrochirus). AB - Before dilution in hypoosmotic media sperm of freshwater fish are maintained quiescent by a range of factors including osmolality, K+ and pH, and the onset of motility is generally associated with an increase in cytoplasmic Ca2+. In contrast, Ca2+ in conjunction with osmolality was found to inhibit motility of intact bluegill sperm. Consistent with seminal plasma composition, 0.16 mmol/L Ca2+ and greater, in conjunction with an osmotic concentration of 290 mOsm/kg, inhibited the onset of bluegill sperm motility; sperm diluted in saline at 290 mOsm/kg without Ca2+ became motile. Cations Mn2+ and Sr2+, in conjunction with osmolality, had an inhibitory effect on initiation of sperm motility similar to that of Ca2+. Sperm motility was inhibited by Ca2+ channel blockers nimodipine and nifedipine, the mitochondrial Ca2+ uniporter inhibitor ruthenium red and the calmodulin inhibitors W-7 and trifluoperazine dihydrochloride. These results provide evidence that elevated cytoplasmic Ca2+ inhibits sperm motility and yet low levels permit or promote motility. This study demonstrates a unique inhibitory action of Ca2+ on the motility of intact fish sperm at physiologically relevant levels. PMID- 17724676 TI - Liquid-based cytology versus conventional Papanicolaou smear in an organized screening program : a prospective randomized study. AB - BACKGROUND: The objective of this study was to evaluate whether liquid-based cytology (LBC) can improve high-standard cervical cancer screening cytology further. The primary endpoint was histopathologic high-grade lesions in current and subsequent screening rounds. The secondary endpoints were cytologic diagnosis and inadequate samples. METHODS: Women were randomized to smear taking by conventional Papanicolaou (Pap) smear or LBC according to the time of appointment. Eight thousand eight hundred ten conventional Pap smears and 4674 LBC samples were included. Evaluations of atypical cytology and referral to colposcopy and treatment were performed as routine procedures. Histopathologic diagnoses were retrieved from a regional database 8 months after the study was closed. The mean follow-up was 2 years and 9 months. RESULTS: Inadequate samples were observed in 0.3% of LBC samples versus 0.7% of Pap smears (P = .002). The total fraction of nonbenign diagnoses in cytology was 4.5% versus 3.5%, respectively (P < .001). Histopathologic evaluation was made on 570 patients constituting 4.6% of the LBC samples and 4% of the Pap smears. Forty percent more high-grade lesions were identified as a result of LBC sampling (1.20% vs 0.85%; P = .05). The influence of the sampling method was significant for all variables (odds ratio [OR], 1.60; 95% confidence interval [95% CI], 1.12-2.28) for high grade lesions that were identified by histology when adjusting for age and screening unit in a logistic regression model. At the second follow-up 2 years and 1 month later, the OR was decreased only slightly (1.51; 95% CI, 1.13-2.01). CONCLUSIONS: In the ongoing cervical screening program of western Sweden, liquid cytology produced a significantly higher yield of histologic high-grade lesions compared with conventional Pap smears. PMID- 17724678 TI - Abnormal cervicovaginal cytology with negative human papillomavirus testing. AB - BACKGROUND: Human papillomavirus (HPV) testing has become part of cervicovaginal diagnostics in many laboratories. False-negative HPV results, even if rare, are potentially relevant clinically, particularly when testing is used alone. In this study, the authors investigated the occurrence and causes of abnormal cervicovaginal cytologies with negative HPV testing. METHODS: The study was performed on 4130 liquid-based cytology (LBC) specimens from 2918 women who had abnormal cervical cytology or colposcopy or a history of abnormal cervical smear. HPV testing with Hybrid Capture II was repeated in LBC specimens with obviously atypical cytology (squamous intraepithelial lesion or abnormal squamous cells, cannot exclude high-grade lesion) and initial negative test results. The results were compared with the follow-up results and with the cytologic features of the specimens. RESULTS: Of 4130 LBC specimens, 94 (2.28%) showed obviously abnormal cells despite negative HPV results, and 50 of those 94 samples (53.19%) were HPV positive on a repeated testing of the same specimen. Histologic follow-up showed high-grade intraepithelial lesion or carcinoma in 10 specimens that initially were negative for HPV. Eight of those samples were HPV-positive on testing repetition. Both specimens that had persistently negative results had poor quality cytologic samples at revision. CONCLUSIONS: High-grade lesions may be identified in the follow-up of HPV-negative specimens with abnormal cytology. Testing repetition in patients with discordant cytology may prevent most potentially clinically relevant false-negative HPV results. PMID- 17724679 TI - Evaluation of quantity and staining pattern of human papillomavirus (HPV) infected epithelial cells in thin-layer cervical specimens using optimized HPV CARD assay. AB - BACKGROUND: Testing for human papillomavirus (HPV) is used in the triage of women with a cervical cytology of atypical squamous cells of undetermined significance (ASCUS). A fluorescent in situ hybridization assay was developed for the detection of HPV using the catalyzed receptor deposition technique (HPV-CARD). In this study, the utility of this assay was tested for the detection of HPV in liquid-based cervical cytology specimens. METHODS: A total of 195 liquid-based cytology specimens were analyzed using the HPV-CARD assay. The results from the assay were compared with HPV polymerase chain reaction (PCR) and typing results. The number of HPV-infected cells and the staining pattern was correlated with the cytology classification. RESULTS: A 91% concordance between HPV-CARD and PCR was observed for the detection of high-risk HPV viruses. A 78% concordance was observed for specimens that were negative for HPV. In ASCUS, low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL) categories, the average number of HPV-positive cells per slide was 19 cells, 127 cells, and 450 cells, respectively. The number of cells with a punctate staining, suggestive of HPV integration, was 21% in ASCUS, 34% in LSIL, and 46% in HSIL specimens. CONCLUSIONS: The results of the current study indicate positive correlations between the severity of the disease and the increased overall quantity of HPV-positive epithelial cells in cervical cytology specimens and accumulation of cells with punctate staining suggestive of integrated HPV. In summary, the developed HPV-CARD assay was found to provide novel information regarding the proportion and staining pattern of HPV-infected epithelial cells in different cytologic categories of cervical specimens. PMID- 17724680 TI - Quality of integrated care for patients with nonsmall cell lung cancer: variations and determinants of care. AB - BACKGROUND: In the current study, the authors focused on determinants influencing the quality of care and variations in the actual quality of integrated care for patients with nonsmall cell lung cancer (NSCLC) to estimate whether there is room for improvement. METHODS: The authors tested the quality of integrated care for 276 NSCLC patients with 14 quality indicators of professional (4 indicators), organizational (3 indicators), and patient-oriented quality (7 indicators). Patient characteristics and actual care data were derived from medical record data, patient-oriented care was derived from patient questionnaires, and professional and hospital characteristics were derived from questionnaires for professionals. The performance measure was the proportion of patients to whom the indicator applied who had positive scores on the indicator. Multilevel logistic regression analysis determined the influence of patient, professional, and hospital characteristics on care. RESULTS: With regard to professional quality, the proportions of patients who underwent fluorodeoxyglucose-positron emission tomography or cervical mediastinoscopy according to the guideline criteria were 88% and 84%, respectively. Only 50% of the biopsies were adequately obtained during mediastinoscopy, and in 3% of the patients with clinical stage III disease (based on the TNM classification) there was a search for brain metastases before the initiation of combination therapy. With regard to organizational quality, the diagnostic route of 79% of the patients was completed within 21 days; 51% of patients began therapy within 35 days and 57% were discussed during multidisciplinary consultation. All but 1 patient-oriented quality indicator scored /=20% with regard to 11 of the 14 indicators. The patient-related determinants "stage of disease," "age," and "comorbidity" were found to influence the indicator scores the most. CONCLUSIONS: The quality of integrated care (especially patient-oriented care) for NSCLC patients needs improvement. Patient characteristics appear to influence performance more than professional or hospital characteristics. PMID- 17724681 TI - Spinal metastases from myxoid liposarcoma warrant screening with magnetic resonance imaging. AB - BACKGROUND: Myxoid liposarcoma (MLS) has an unusual tendency for extrapulmonary metastasis, particularly to the spine and soft tissues. The objective of this study was to determine the prevalence of spinal metastasis, treatment outcomes, and optimal screening method for spinal metastasis in patients with MLS. METHODS: Data from patients with had spinal metastases were obtained from the authors' institutional soft tissue sarcoma database. The accuracy with which positron emission tomography (PET) scans and bone scans identified metastatic lesions was compared with the accuracy of magnetic resonance imaging (MRI). Clinical response to treatment was based on pain, neurologic scores, and survivorship analysis. RESULTS: There were 33 patients who developed spinal metastasis after a median 36 months of follow-up (range, from 7.5 months to 33 years). Known spinal metastases were detected by bone scans in 16% of patients and by PET scans in 14% of patients. Patients who underwent surgery had high-grade spinal cord compression more often than patients who did not undergo surgery (72% vs 19%, respectively; P = .002). Pain and neurologic function were improved or maintained in all patients who received radiation alone (n = 8 patients) and in all but 1 patient who underwent surgery (n = 18 patients). The median overall survival was 51.4 months from the time of primary diagnosis and 21.9 months from the time of first metastasis. CONCLUSIONS: Bone scans and PET scan lack sufficient sensitivity to detect spinal metastasis from MLS. Treatment of metastasis is palliative, but local treatment can yield long-term disease control in select patients. Screening with whole-spine MRI may lead to the earlier detection of spinal metastasis. PMID- 17724682 TI - Features at presentation predict children with acute lymphoblastic leukemia at low risk for tumor lysis syndrome. AB - BACKGROUND: Tumor lysis syndrome (TLS) is a well-recognized complication of acute lymphoblastic leukemia (ALL). The ability to predict children at differing risk of TLS would be an early step toward risk-based approaches. The objectives of the current study were 1) to describe the prevalence and predictors of TLS in childhood ALL and 2) to develop a sensitive prediction rule to identify patients at lower risk of TLS. METHODS: Health records of children aged /=2 laboratory abnormalities occurring in the time frame of interest. Predictors of TLS were determined using univariate and multiple logistic regression analyses. RESULTS: Among 328 patients, 23% met criteria for TLS. Factors predictive of TLS were male sex (odds ratio [OR], 1.8; P = .041), age >/=10 years (OR, 4.5; P < .0001), splenomegaly (OR, 3.3; P < .0001), mediastinal mass (OR, 12.2; P < .0001), T-cell phenotype (OR, 8.2; P < .0001), central nervous system involvement (OR, 2.8; P = .026), lactate dehydrogenase >/=2000 U/L (OR, 7.6; P < .0001), and white blood count (WBC) >/=20 x 10(9)/L (OR, 4.7; P < .0001). Among variables that were available at presentation, multiple regression analysis identified age >/=10 years, splenomegaly, mediastinal mass, and initial WBC >/=20 x 10(9)/L as independent predictors of TLS. When all 4 of those predictors were absent at presentation (n = 114 patients), the negative predictive value of developing TLS was 97%, with a sensitivity of 95%. CONCLUSIONS: Clinical and laboratory features at the time of presentation identified a group of children with ALL at low risk for TLS that may benefit from a risk-stratified approach directed at reduced TLS monitoring and prophylaxis. PMID- 17724683 TI - Distinct signaling mechanisms activate the target of rapamycin in response to different B-cell stimuli. AB - Phosphoinositide 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR), a downstream kinase, are both required for proliferation of splenic B cells. However, the functions of PI3K and mTOR in response to different stimuli and among B cell subsets have not been fully elucidated. We used flow cytometry and magnetic cell sorting to examine the requirement for PI3K and mTOR in responses of splenic B cell subsets to BCR and LPS stimulation. BCR-mediated phosphorylation of Akt and Erk is sensitive to the PI3K catalytic inhibitor wortmannin in both marginal zone (MZ) and follicular (FO) cells. BCR-mediated mTOR activation in both subsets is inhibited by wortmannin, though less strongly in MZ cells. In contrast, LPS-induced mTOR signaling is strikingly resistant to wortmannin in both subsets. Similarly, functional responses to LPS are partially wortmannin resistant yet sensitive to mTOR inhibition by rapamycin. We also observed mitogen-independent mTOR activity that is regulated by nutrient availability, and is significantly elevated in MZ cells relative to FO cells. These data define both similarities and differences in PI3K/mTOR signaling mechanisms in MZ and FO cells, and suggest that mTOR signaling can occur in the absence of PI3K activation to promote B cell responses to LPS. PMID- 17724684 TI - Memory phenotype CD8+ T cells with innate function selectively develop in the absence of active Itk. AB - T cells with a memory-like phenotype and possessing innate immune function have been previously identified as CD8(+)CD44(hi) cells. These cells rapidly secrete IFN-gamma upon stimulation with IL-12/IL-18 and are involved in innate responses to infection with Listeria monocytogenes. The signals regulating these cells are unclear. The Tec kinase Itk regulates T cell activation and we report here that a majority of the CD8(+) T cells in Itk null mice have a phenotype of CD44(hi) similar to memory-like innate T cells. These cells are observed in mice carrying an Itk mutant lacking the kinase domain, indicating that active Tec kinase signaling suppresses their presence. These cells carry preformed message for and are able to rapidly produce IFN-gamma upon stimulation in vitro with IL-12/IL-18, and endow Itk null mice the ability to effectively respond to infection with L. monocytogenes or exposure to lipopolysaccharides by secretion of IFN-gamma. Transfer of these cells rescues the ability of IFN-gamma null mice to reduce bacterial burden following L. monocytogenes infection, indicating that these cells are functional CD8(+)CD44(hi) T cells previously detected in vivo. These results indicate that active signals from Tec kinases regulate the development of memory-like CD8(+) T cells with innate function. PMID- 17724685 TI - (tmp)(2)Zn x 2 MgCl(2) x 2 LiCl: a chemoselective base for the directed zincation of sensitive arenes and heteroarenes. PMID- 17724688 TI - Back to the beginning--the quest for thymic epithelial stem cells. AB - Stem cell-based therapies hold much promise for the rejuvenation of aged or damaged tissues; however, before such cells can be used therapeutically, they must first be accurately identified. In this issue of the European Journal of Immunology it is reported that MTS24, a marker previously associated with progenitor cells of the thymic epithelium, fails to accurately identify epithelial cell populations with the ability to reconstitute a functional thymus. This finding demonstrates that much progress needs to be made before thymic epithelial stem cells can be harnessed for clinical benefit. PMID- 17724689 TI - Staying alive--naive CD4(+) T cell homeostasis. AB - The immune system must maintain a broad repertoire of naive T cells in order to respond to the diverse range of pathogens that it will encounter over the course of a lifetime. Although it is known that contact with IL-7 is crucial for the survival of naive T cells, the precise intracellular signals that mediate its effects remain obscure. An article in this issue of the European Journal of Immunology has found that IL-7 requires the coordinated action of multiple pathways to maintain naive CD4(+) T cells. PMID- 17724690 TI - Evaluation of opioid induced nausea and vomiting in sickle cell disease. AB - A common side effect of opioids is nausea and vomiting; however, the incidence in hospitalized patients receiving opioids for acute pain is unknown. We performed a retrospective study in adult patients with sickle cell disease admitted for an acute pain crisis during a six-month period to evaluate the incidence of nausea and vomiting and characterize the prescribing of antiemetics. Eligibility included normal hepatic and renal function. Thirty-four subjects with a total of 97 admissions were evaluated. As expected, opioids were prescribed during all admissions. Fifty percent of the subjects experienced nausea or vomiting during the study period and these same patients accounted for the majority of the admissions, 17 subjects with 71 admissions (Group I). Nausea was reported in 18 (25%) of these admissions and vomiting was reported in 24 (34%) of these admissions. The most common antiemetics prescribed were: prochlorperazine, metoclopramide, and promethazine and antiemetics were ordered during 22 (23%) separate admissions for all subjects included in the study. The clinical benefit of these medications is limited due to uneven documentation. In conclusion, many of our patients experienced nausea or vomiting with antiemetics infrequently prescribed on an as needed basis. This suggests a need for better approaches to manage nausea and vomiting in patients receiving opioids. PMID- 17724695 TI - Influence of microemulsion chirality on chromatographic figures of merit in EKC: results with novel three-chiral-component microemulsions and comparison with one- and two-chiral-component microemulsions. AB - Novel microemulsion formulations containing all chiral components are described for the enantioseparation of six pairs of pharmaceutical enantiomers (atenolol, ephedrine, metoprolol, N-methyl ephedrine, pseudoephedrine, and synephrine). The chiral surfactant dodecoxycarbonylvaline (DDCV, R- and S-), the chiral cosurfactant S-2-hexanol, and the chiral oil diethyl tartrate (R- and S-) were combined to create four different chiral microemulsions, three of which were stable. Results obtained for enantioselectivity, efficiency, and resolution were compared for the triple-chirality systems and the single-chirality system that contained chiral surfactant only. Improvements in enantioselectivity and resolution were achieved by simultaneously incorporating three chiral components into the aggregate. The one-chiral-component microemulsion provided better efficiencies. Enantioselective synergies were identified for the three-chiral component nanodroplets using a thermodynamic model. Additionally, two types of dual-chirality systems, chiral surfactant/chiral cosurfactant and chiral surfactant/chiral oil, were examined in terms of chromatographic figures of merit, with the former providing much better resolution. The two varieties of two chiral-component microemulsions gave similar values for enantioselectivity and efficiency. Lastly, the microemulsion formulations were divided into categories based on the number of chiral microemulsion reagents and the average results for each pair of enantiomers were analyzed for trends. In general, enantioselectivity and resolution were enhanced while efficiency was decreased as more chiral components were used to create the pseudostationary phase (PSP). PMID- 17724696 TI - Analysis of inflammatory biomarkers from tissue biopsies by chip-based immunoaffinity CE. AB - To aid in the biochemical analysis of human skin biopsies, a semiautomatic chip based CE system has been developed for measuring inflammatory biomarkers in microdissected areas of the biopsy. Following solubilization of the dissected tissue, the desired biomarkers were isolated by immunoaffinity capture using a panel of 12 antibodies, immobilized on a disposable glass fiber disk, within the extraction port of the chip. The captured analytes were labeled with a 635 nm light-emitting laser dye and electroeluted into the separation channel. Electrophoretic separation of all of the analytes was achieved in 2.2 min with quantification of each peak being performed by online LIF detection and integration of each peak area. Comparison of the results obtained from the chip based system to those obtained using commercially available high-sensitivity immunoassays demonstrated that the chip-based assay provides a fast, accurate procedure for studying the concentrations of inflammatory biomarkers in complex biological materials. The degree of accuracy and precision achieved by the chip based CE is comparable to conventional immunoassays and the system is capable of analyzing circa six samples per hour. With the ever-expanding array of antibodies that are commercially available, this chip-based system can be applied to a wide variety of different biomedical analyses. PMID- 17724697 TI - Single-run separation of cationic, anionic, and polyanionic compounds by CE-ESI MS. AB - A method for a single-run separation of cationic, anionic, and polyanionic compounds by CE hyphenated to ESI MS (CE-ESI-MS) is described. One of the main issues for coupling CE to MS with an ESI source consists in maintaining an electric contact for the electrophoretic separation. This condition is only performed if a liquid flow arising from the separation capillary is directed to the needle, making it coupling-compatible. This latter situation is incompatible with the separations of polyanionic compounds of higher electrophoretic mobility (in absolute value) than the electroosmotic mobility, performed in bare fused silica capillaries under a negative polarity. In this study, several alternative approaches were evaluated to circumvent this difficulty, and applied to the setup of the CE-MS separation of a mixture containing both cationic and polyanionic compounds, which are synthesis intermediates of contrast agents for medical imaging. Eventually, the detection of the cationic and anionic compounds in a single run could be obtained by either using neutrally coated polymethylsiloxane (DB-1) capillaries and simultaneously applying a negative voltage polarity and a pressure allowing to compensate for the residual cathodic EOF or by dynamically modifying the inner wall of a bare fused-silica capillary with a polycationic polymer (hexadimethrine bromide) and using it afterwards under negative voltage polarity. PMID- 17724698 TI - Coupling CE with atmospheric pressure photoionization MS for pharmaceutical basic compounds: optimization of operating parameters. AB - The use of CE coupled with MS (CE-MS) has evolved as a useful tool to analyze charged species in small sample volumes. Because of its sensitivity, versatility and ease of implementation, the ESI interface is currently the method of choice to hyphenate CE to MS. An alternative can be the atmospheric pressure photoionization (APPI) source, however, numerous parameters must be optimized for its coupling to CE. After evaluation of the sheath liquid composition and the CE capillary outlet position, an experimental design methodology was assessed for optimizing other ionization source parameters, such as sheath liquid flow rate, drying gas flow rate and temperature, nebulizing gas pressure, vaporizer temperature, and capillary voltage. For this purpose, a fractional factorial design (FFD) was selected as a screening procedure to identify factors which significantly influence sensitivity and efficiency. A face-centered central composite design (CCD) was then used to predict and optimize sensitivity, taking into account the most relevant variables. Sensitivity was finally evaluated with the optimized conditions and height-to-noise ratios (H/N) around 10 were achieved for an injection of 200 ng/mL of each analyte. PMID- 17724700 TI - UGT2B7 promoter variant -840G>A contributes to the variability in hepatic clearance of morphine in patients with sickle cell disease. AB - The purpose of the study was to determine if UDP-glucuronosyltransferase (UGT) 2B7 allelic variants encoding for UGT2B7, primary enzyme responsible for morphine glucuronidation contribute to the variability in the hepatic clearance of morphine in sickle cell disease (SCD). Twenty-four hour PK study of morphine and UGT2B7 variants genotyping was performed in 20 SCD patients in a steady state of health. Presence of the -840G allele (GG and GA) was associated with lower morphine metabolites/morphine AUC ratio compared with AA genotype (1.8 +/- 0.5 vs. 3.0 +/- 1.8 for M6G/M and 10.1 +/- 2.7 vs. 15.7 +/- 9.4 for M3G/M) (P = 0.03). Presence of UGT2B7 -840G allele is associated with significantly reduced glucuronidation of morphine and thus contributes to the variability in hepatic clearance of morphine in SCD. PMID- 17724699 TI - Pulmonary hypertension associated with sickle cell disease: clinical and laboratory endpoints and disease outcomes. AB - Screening for pulmonary hypertension (pHTN) has not yet become routine in sickle cell disease (SCD), despite clinical evidence of its high prevalence and associated mortality. Our objectives are to identify clinical conditions and laboratory findings predictive of/or associated with pHTN. One hundred twenty five adult outpatients with Hb SS, SC, SOArab, Sbeta(0), or Sbeta(+) thalassemia, who underwent echocardiography and/or right heart catheterization due to cardiorespiratory symptoms, were studied. pHTN was identified in 36% (28/77) of SS/Sbeta(0) and in 25% (12/48) of SC/SOArab/Sbeta(+) patients studied. In SS/Sbeta(0) patients, pHTN was associated with low hemoglobin, low GFR, increasing age, no history of treatment with hydroxyurea and a history of leg ulcers, with trends for associations with higher total bilirubin, LDH levels, systolic systemic blood pressure, history of avascular necrosis, seizures, and cerebrovascular events. Twelve (40%) of the SS/Sbeta(0) patients with pHTN had >or= 1+ proteinuria. (P<0.039). The presence of proteinuria correlated with lower GFR and had a high positive predictive value (0.60) for pHTN in subjects with SS/Sbeta(0). The data also provided evidence that pHTN in this population is associated with right heart failure, with echocardiographic evidence of right ventricle enlargement and pericardial effusion. This study confirmed that even relatively mild elevations in pulmonary pressure are associated with high prospective mortality (hazard ratio: 15.9). We concluded that pHTN has a high prevalence in all Hb S related syndromes and is associated with increased mortality in SS/Sbeta(0). Kidney dysfunction, as indicated by proteinuria or decreased GFR, also represents sufficient reason to screen for pHTN. PMID- 17724701 TI - Clinical trials in sickle cell disease: adopting the combination chemotherapy paradigm. PMID- 17724702 TI - Causes and diagnosis of copper deficiency. PMID- 17724703 TI - Could treatment with neohepatocytes benefit patients with decompensated chronic liver disease? PMID- 17724705 TI - Detection of circulating tumor cells in the peripheral blood of patients with androgen-independent, advanced or metastatic prostate cancer. PMID- 17724704 TI - Mutations and polymorphisms in hemoglobin genes and the risk of pulmonary hypertension and death in sickle cell disease. AB - Pulmonary hypertension is a common complication of sickle cell disease (SCD) and a risk factor for early death. Hemolysis may participate in its pathogenesis by limiting nitric oxide (NO) bioavailability and producing vasculopathy. We hypothesized that hemoglobin mutations that diminish hemolysis in SCD would influence pulmonary hypertension susceptibility. Surprisingly, coincident alpha thalassemia (Odds Ratio [OR]=0.95, 95% CI=0.46-1.94, P=NS) was not associated with pulmonary hypertension susceptibility in homozygous SCD. However, pulmonary hypertension cases were less likely to have hemoglobin SC (OR=0.18, 95% confidence interval [CI]=0.06-0.51, P=0.0005) or Sbeta(+) thalassemia (OR=0.25, 95% CI=0.06-1.16, P=0.10). These compound heterozygotes may be protected from pulmonary hypertension because of reduced levels of intravascular hemolysis, but develop this complication at a lower rate possibly due to the presence of non hemolytic risk factors such as renal dysfunction, iron overload and advancing age. Despite this protective association, patients with SC who did develop pulmonary hypertension remained at significant risk for death during 49 months of follow-up (Hazard Ratio=8.20, P=0.0057). PMID- 17724706 TI - Peripheral blood monocytes from patients with HBV related decompensated liver cirrhosis can differentiate into functional hepatocytes. AB - Peripheral blood monocytes (PBMCs) have the potential to differentiate into various progenitor cells. Here we have investigated the differentiation potential of PBMCs derived from patients with HBV related decompensated liver cirrhosis into hepatocyte-like cells. In our clinical trial, the PBMCs from 2 patients were mobilized by the recombinant human granulocyte colony stimulating factor, followed by leukapheresis and transplantation of PBMCs. PBMCs, induced by recombinant human hepatocyte growth factors, were identified by the expression of hepatocyte markers and specific biological functions with biochemical assays in vitro. Patients showed a lasting clinical amelioration for more than one year after transplantation, and hepatocyte-like cells were identified by expressing liver specific genes, synthesizing albumin, urea, aspirate transaminase, and glycogen, which were all similar to the human normal hepatic cell line QZG. Our results clearly demonstrated that mobilized PBMCs from patients with HBV related decompensated liver cirrhosis could differentiate into functional hepatocyte-like cells, indicating the possibility of autologous cell transplantation for treating patients with HBV related decompensated liver cirrhosis. PMID- 17724707 TI - Prognostic significance of synaptophysin in stage I of squamous carcinoma and adenocarcinoma of the lung. AB - BACKGROUND: The prognostic significance of the presence of a neuroendocrine marker (synaptophysin, SY) was analyzed in stage I of squamous carcinoma and adenocarcinoma of the lung. METHODS: A multicentric retrospective study was conducted with immunohistochemical staining in a single center of 318 patients resected for squamous carcinoma or adenocarcinoma in pathologic stage I. RESULTS: In all, 162 cases of squamous carcinoma and 156 cases of adenocarcinoma were identified, which included 105 patients in stage IA (50 patients with squamous carcinoma and 55 patients with adenocarcinoma) and 213 in stage IB (112 with squamous carcinoma and 101 with adenocarcinoma). Eighty-six tumors showed a presence of SY+ (27%). Univariate analysis showed lower survival rates at 5 years for those patients older than 70 years of age compared with those patients younger than 70 years of age (60.35% vs 70.57%; P = .007) and for those patients with SY+ compared with those with SY- (52.48% vs 72.68%; P = .0017). Patients with SY+ tumors showed a higher rate of recurrence than patients with SY- tumors (50% vs 33.6%; P = .008). Multivariate analysis showed that those patients greater that 70 years of age (hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.14-2.65) and the presence of SY (HR, 2.15; 95% CI, 1.40-3.30) were significant independent prognostic factors associated with a poor outcome. CONCLUSIONS: Stage I of squamous carcinoma and adenocarcinoma of the lung with SY+ has a poor prognosis, with a higher frequency of recurrence and lower survival rates. PMID- 17724709 TI - Hypertriglyceridemia presenting as "pink blood" and elevated hemoglobin level. PMID- 17724708 TI - The impact of hepatitis B viral load on recurrence after complete necrosis in patients with hepatocellular carcinoma who receive transarterial chemolipiodolization: implications for viral suppression to reduce the risk of cancer recurrence. AB - BACKGROUND: Hepatocellular carcinoma (HCC) has a high tendency for recurrence after radical treatment. Apart from tumor and liver function parameters, little is known about the role of hepatitis B virus (HBV) factors in the recurrence of HCC. The objective of this study was to identify the potential relation between viral load and HCC recurrence in patients undergoing transarterial chemolipiodolization. METHODS: This was a cohort study of 62 consecutive patients who had HBV-related HCC and achieved complete necrosis with transarterial chemolipiodolization. Risk factors, including viral load for posttreatment recurrence, were analyzed. RESULTS: Overall, 32 of 62 patients (51.6%) developed a recurrence during the study period (7.2-37.5 months). Multivariate analysis established Child-Pugh Class B (P = .014), multiple tumors (P = .013), and high viral load (HBV DNA levels >10(5) copies/mL) at complete necrosis (P = .001) as independent risk factors for recurrence. On both univariate and multivariate analyses, high viral load at the time of complete necrosis was identified as the strongest factor for recurrence; moreover, its statistically significant effects still were observed even when conducting the analyses separately for both local recurrence (P = .018) and distant recurrence (P = .009). CONCLUSIONS: Among individuals who underwent transarterial chemolipiodolization, high HBV viral load at complete necrosis was among the most important risk factors for posttreatment recurrence, irrespective of the locational pattern of recurrence. The current findings underscored the need for future work that tests the applicability of antiviral therapy to reduce the risk of HCC recurrence in this setting. PMID- 17724710 TI - Spermiogenesis in soft-shelled turtle, Pelodiscus sinensis. AB - Spermiogenesis in the soft-shelled turtle, Pelodiscus sinensis, was examined by transmission electron microscopy. The process includes nuclear elongation, chromatin condensation, acrosomal and flagellar development, and elimination of excess cytoplasm. In stage I, the proacrosomal vesicle occurs next to a shallow fossa of the nucleus, and a dense acrosomal granule forms beneath it. A smaller subacrosomal granule in the middle of the fibrous layer is related to the development of intranuclear tubules. The nucleus begins to move eccentrically. In stage II, the round proacrosomal vesicle is flattened by protrusion of the nuclear fossa, and the dense acrosomal granule diffuses into the vesicle, as the fibrous layer forms the subacrosomal cone. Circular manchettes develop around the nucleus, and the chromatin coagulates into small granules. The movement of the nucleus causes rearrangement of the cytoplasm. In stage III, the front of the elongating nucleus protrudes out of the spermatid and is covered by the flat acrosome; coarse granules replace the small ones within the nucleus. At the posterior pole of the head, mitochondria move backward. Numerous microtubules begin to assemble the axoneme of flagellum. In stage IV, the chromatin concentrates to dense homogeneous phase. The circular manchette is reorganized longitudinally. The Sertoli process covers the acrosome and the residues of the cytoplasmic lobes are eliminated. In stage V, the sperm head matures. After dissolution of the longitudinal manchette, the mitochondria arrange themselves around the proximal and distal centrioles. Caudal to the mitochondrial mass, a fibrous sheath surrounds the proximal portion of the flagellum. PMID- 17724711 TI - Late deposition of elastin to vertical microfibrillar fibers in the presumptive dermis of the chick embryonic tarsometatarsus. AB - Fibrillin microfibrils are integral components of elastic fibers and serve as a scaffold for elastin deposition. However, microfibrillar fibers (MFs) are not necessarily committed to develop into so-called elastic fibers. In dermis, elastin-free oxytalan MFs originating from the dermoepidermal junction are continuous to elaunin-type MFs (with a small amount of elastin) in the deeper papillary dermis, whereas the reticular dermis contains elastic fibers, or MFs embedded largely in elastin. In this study, we have investigated temporospatial patterns of elastin deposition on the MFs in tarsometatarsal presumptive dermis. While the earliest expression of elastin was demonstrated immunohistochemically as early as embryonic day 4 (ED4) in the wall of cardiac outflow and pharyngeal arch arteries, its deposition in the tarsometatarsus was first detected at ED6 in the deeper mesenchyme and at ED13 in the subectodermal mesenchyme. In the latter tissue, MFs had been organized perpendicularly to the covering ectoderm by ED4, well before an overt accumulation of collagenous matrix. Elastin deposition was observed initially in a punctate manner at ED13 and afterward became continuous along MFs. However, a characteristic spaced array of subectodermal vertical MFs was disorganized by ED17. These findings suggest that elastin deposition in the subectodermal MFs is not deployed by continuous, orderly propagation from elastic fibers in the deeper mesenchyme but occurs de novo in multiple foci along vertical MFs. Moreover, the present chronology of elastin deposition indicates that subectodermal, elastin-free MFs function as a transient, but primary fibrous structure in the presumptive dermis before the accumulation of collagenous matrix. PMID- 17724712 TI - Lobe identity in the Mongolian gerbil prostatic complex: a new rodent model for prostate study. AB - Knowledge of structural and physiological differences among the prostatic lobes (PL) is the basis for development of experimental studies in traditional laboratory rodents. Although Mongolian gerbil reproductive organs have been increasingly investigated, its prostate structure is far from being properly known, and investigations of this organ focused on the ventral lobe (VL). Thus, the present study provides a thorough morphological description of prostatic complex in the male adult gerbil on the basis of topographic, histological, and ultrastructural analysis and ductal branching. Like other rodents, four pairs of PL were observed. However, in contrast to the rat and mouse, the VL is the least voluminous component and the dorsolateral lobe (DLL) is the most prominent and spatially isolated from remaining PL. The occurrence of a dorsal lobe (DL), hidden between bladder and insertion of seminal vesicles, has not been mentioned in previous reports with Mongolian gerbil. Collagenase digestion followed by microdissection revealed that, except for DL, which has a tubular-acinar organization, all PL exhibit tubular organization and variable ductal branching. Distinct histological and ultrastructural features such as secretory epithelium, aspect of luminal secretion and stromal organization are reported for each PL and are confirmed by morphometric and stereological methods. Histological sections showed at least three intralobar segments in VL and DL. Ultrastructural analysis evidenced that, although luminal epithelial cells of PL share typical features of exocrine secretory cells, there are striking lobe phenotypical variations. Both merocrine and apocrine pathways are observed in variable rates in all PL, with the predominance of the former in the DLL and the latter in the CG. The morphological observations presented herein point to distinct structural identities for each PL, which probably reflects specific functional compromise of seminal fluid secretion. These data also point to the gerbil as a good model for investigations concerning the regulation of prostate development and homeostasis, mainly with regard to the dorsal and dorsolateral PL. PMID- 17724713 TI - Mechanism of formation of human calcium oxalate renal stones on Randall's plaque. AB - Although calcium oxalate (CaOx) renal stones are known to grow attached to renal papillae, and specifically to regions of papillae that contain Randall's plaque (interstitial apatite deposits), the mechanisms of stone overgrowth on plaque are not known. To investigate the problem, we have obtained biopsy specimens from two stone patients that included an attached stone along with its tissue base and have studied the ultrastructural features of the attachment point using light and transmission electron microscopy, Fourier transform infrared spectroscopy (mu FTIR), and immunohistochemical analysis. The epithelium is disrupted at the attachment site. The denuded plaque that borders on the urinary space attracts an envelope of ribbon-like laminates of crystal and organic matrix arising from urine ions and molecules. Into the matrix of this ribbon grow amorphous apatite crystals that merge with and give way to the usual small apatite crystals imbedded in stone matrix; eventually CaOx crystals admix with apatite and become the predominant solid phase. Over time, urine calcium and oxalate ions gradually overgrow on the large crystals forming the attached stone. PMID- 17724714 TI - Combining adenoviral oncolysis with temozolomide improves cell killing of melanoma cells. AB - Oncolytic adenoviruses are emerging agents for treatment of cancer by tumor restricted virus replication, cell lysis and virus spread. Clinical studies with first generation oncolytic adenoviruses have revealed that an increased potency is warranted in order to achieve therapeutic efficacy. One approach towards this end is to combine adenoviral oncolysis with chemotherapy. Here, a fundamental requirement is that chemotherapy does not interfere with adenovirus replication in cancer cells. We have previously developed a melanoma-targeted oncolytic adenovirus, Ad5/3.2xTyr, which features tyrosinase promoter regulated replication and enhanced cell entry into melanoma cells. In this study, we investigated a combination treatment of melanoma cells with Ad5/3.2xTyr and temozolomide (TMZ), which produces the same active metabolite as Dacarbazine/DTIC, the standard chemotherapy for advanced melanoma. We report that TMZ does not inhibit adenovirus replication in melanoma cells. Additive or synergistic cell killing of melanoma cells, dependent on the cell line used, was observed. Enhanced cell binding was not responsible for synergism of adenoviral oncolysis and TMZ treatment. We rather observed that higher numbers of virus genomes are produced in TMZ-treated cells, which also showed a cell cycle arrest in the G2 phase. Our results have important implications for the clinical implementation of adenoviral oncolysis for treatment of malignant melanoma. It suggests that such studies are feasible in the presence of TMZ or DTIC chemotherapy and recommends the investigation of a viro-chemo combination therapy. PMID- 17724715 TI - The impact of new technologies in cervical cancer screening: results of the recruitment phase of a large randomised controlled trial from a public health perspective. AB - The decision to introduce liquid-based cytology (LBC) and HPV as screening tests involves criteria based on resource consumption. We used cross-sectional data at recruitment from the NTCC trial [ISRCTN81678807] on 28,000 women aged 35-60, randomised to receive a conventional Pap test or LBC plus HPV. We computed the resources employed to detect a CIN2+ with different screening strategies. In order to result in the same overall cost per CIN2+ detected as screening by conventional cytology, the unit cost of LBC used alone should be less than that of a conventional Pap while its unit cost may be up to 20% higher if HPV-triage for Atypical Squamous Cells of Undetermined Significance is applied together. With the same criterion the unit cost of HPV used alone may be about 20% higher than that of a Pap-test using a 1 pg/ml cut-off and over 40% higher using a 10 pg/ml cut-off. If HPV testing is applied with cytology-triage, a single HPV test may cost 20-30% more than a conventional Pap to result in the same overall cost per CIN2+ detected. PMID- 17724716 TI - Early detection of cervical neoplasia by Raman spectroscopy. AB - Early detection of malignant tumours, or their precursor lesions, improves patient outcome. High risk human papillomavirus (HPV), particularly HPV16, infection can lead to the development of uterine cervical neoplasia, and therefore, the identification in clinical samples of the effects of HPV infection may have clinical value. In this report, we apply Raman microspectroscopy to live and fixed cultured cells to discriminate between defined cell types. Raman spectra were acquired from primary human keratinocytes (PHK), PHK expressing the E7 gene of HPV 16 (PHK E7) and CaSki cells, an HPV16-containing cervical carcinoma-derived cell line. Averaged Raman spectra showed variations, mostly in peaks originating from DNA and proteins, consistent with HPV gene expression and cellular changes associated with neoplasia, in both live and fixed cells. Principal component analysis produced good discrimination between the cell types, with sensitivities of up to 100% for the comparison of fixed PHK and CaSki. These results demonstrate the ability of Raman spectroscopy to discriminate between cell types representing different stages of cervical neoplasia. More specifically, this technique was able to identify cells expressing the HPV 16 E7 gene accurately and objectively, suggesting that this approach may be of value in diagnosis. Moreover, the ability to detect the effects of the virus in fixed samples also demonstrates the compatibility of Raman spectroscopy with current cervical screening methods. (c) 2007 Wiley-Liss, Inc. PMID- 17724717 TI - Misclassification of colorectal cancer stage and area variation in survival. AB - We previously investigated the impact of health area of residence on colon and rectal cancer survival by estimating area-specific relative excess risk of death (RER), stratified by stage at diagnosis. The aims of this study were to quantify errors in colorectal cancer stage obtained from an Australian population-based cancer registry and assess the potential impact of errors in stage on these estimates. For a subset of cases, we compared the cancer registry stage with that from a survey of treating surgeons. We then randomly reallocated all cases to a simulated "corrected" stage according to the estimated misclassification probabilities and repeated the analysis of area variation stratified by simulated stage 1,000 times. We found 70% agreement between the Registry and Survey stage. This reallocation of the Registry cases by stage resulted in substantial variation in area-specific RERs across the simulated samples. Area variation in survival for localized colon and localized rectal cancer, which were previously statistically significant when classified using Registry stage, appeared no longer to be so. Misclassification of cancer registry stage can have an important impact on estimates of spatial variation in stage-specific colon and rectal cancer survival. If population-based cancer registry data are to be effectively used in evaluating and improving cancer care, the quality of the stage data may need to be improved. PMID- 17724718 TI - Osteonectin downregulates E-cadherin, induces osteopontin and focal adhesion kinase activity stimulating an invasive melanoma phenotype. AB - Osteonectin is recognised as a marker of metastasis progression in melanoma and has been implicated in the transition from radial to vertical growth phase. A Tetracycline-inducible system was used to regulate Osteonectin protein levels in melanoma cell lines to examine the morphological, biochemical and invasive changes that accompany its altered expression. Assay of protein and phosphorylation changes showed a downregulation of E-cadherin, upregulation of Osteopontin and a corresponding increase in phosphorylation of Focal Adhesion Kinase on Tyr(397) and Tyr(576) concomitant with Osteonectin induction. Melanoma cells overexpressing Osteonectin displayed increased invasive potential, whereas ablation of Osteonectin gene transcription using siRNA suppressed the invasive potential of these cells and resulted in the upregulation of E-cadherin. The recently described interaction of Osteonectin with Integrin Linked Kinase leading to modulation of its activity suggests a mechanism relevant to the loss of E cadherin and cell adhesion that occurs during melanoma progression. These results indicate a central role for Osteonectin in the regulation of gene expression changes driving the progression of melanoma toward metastasis. PMID- 17724719 TI - Presence of simian virus 40 DNA sequences in diffuse large B-cell lymphomas in Tunisia correlates with aberrant promoter hypermethylation of multiple tumor suppressor genes. AB - The simian virus SV40 (SV40), a potent DNA oncogenic polyomavirus, has been detected in several human tumors including lymphomas, mainly in diffuse large B cell type (DLBCL). However, a causative role for this virus has not been convincingly established. Hypermethylation in promoter regions is a frequent process of silencing tumor suppressor genes (TSGs) in cancers, which may be induced by oncogenic viruses. In this study, we investigated the relationship between the presence of SV40 DNA sequences and the methylation status of 13 TSGs in 108 DLBCLs and 60 nontumoral samples from Tunisia. SV40 DNA presence was investigated by PCR assays targeting the large T-antigen, the regulatory and the VP1 regions. Hypermethylation was carried out by methylation-specific PCR. SV40 DNA was detected in 63/108 (56%) of DLBCL and in 4/60 (6%) of nontumoral samples. Hypermethylation frequencies for the tested TSGs were 74% for DAPK, 70% for CDH1, SHP1, and GSTP1, 58% for p16, 54% for APC, 50% for p14, 39% for p15, 19% for RB1, 15% for BLU, 3% for p53, and 0% for p300 and MGMT. No hypermethylation was observed in nontumoral samples. Hypermethylation of SHP1, DAPK, CDH1, GSTP1 and p16 genes were significantly higher in SV40-positive than in SV40-negative DLBCL samples (p values ranging from 0.0006 to <0.0001). Our findings showed a high prevalence of SV40 DNA in DLBCLs in Tunisia. The significant association of promoter hypermethylation of multiple TSGs with the presence of SV40 DNA in DLBCLs supports a functional effect of the virus in those lymphomas. PMID- 17724720 TI - Family history of urogenital cancers in patients with bladder, renal cell and prostate cancers. AB - Family history of urogenital cancers has been associated with an increased risk of cancer at the same sites. To evaluate the risks of bladder, prostate and renal cell neoplasms for family history of urogenital cancers in first-degree relatives, we analysed data from a case-control study conducted in northern Italy between 1985 and 1992 and including a total of 1,356 incident, histologically confirmed cancer cases: 727 bladder, 348 renal cell and 281 prostate cancer cases. Controls were 1,067 patients admitted to the same network of hospitals for acute, nonneoplastic conditions. Unconditional logistic regression was used to estimate odds ratios (ORs) of urogenital cancers, adjusting for age, sex, study centre, education, body mass index, smoking habit, alcohol consumption and number of brothers and, where appropriate, sisters. ORs of urogenital cancers for subjects with at least 1 first-degree relative with cancer at the same site were 6.1 [95% confidence interval (CI), 2.3-16.6] for bladder, 2.0 (95% CI: 0.6-6.2) for renal cell and 2.0 (95% CI: 0.9-4.1) for prostate cancer. PMID- 17724721 TI - Development and validation of the general module of the system of quality of life instruments for cancer patients. AB - Based on World Health Organization (WHO)'s definition of Quality of Life (QOL) and programmed decision procedures, we developed a general module of the System of Quality of Life Instruments for Cancer Patients (QLICP-GM) utilizing focus group discussions, pilot tests of 448 cases and field tests of 600 cases of 5 different cancer patients. The number of items in the final version was reduced to 32 from a 78-item pool. The psychometric properties of the scale were evaluated by indicators such as validity and reliability coefficients, SRM, and statistical methods of correlational analysis, t tests, and structural equation modeling. Correlational and structural equation model analyses indicate good construct validity with RMSEA 0.086, NNFI 0.947 and CFI 0.961. Good criterion related validity was found when FACT-G was used as the criterion. The test-retest reliability for all domains and the overall scale is above 0.85; the internal consistency alpha for each domain is higher than 0.70 except of the social function; alpha and the split-half reliability of the overall scale is 0.88 and 0.93, respectively. The pre-post changes of QOL scores are of statistical significances in 3 domains of physical function, psychological function, common symptoms and side effects, and the overall instrument, with standardized response mean ranging from 0.16 to 0.67. Equivalence tests showed nonequivalence on quality of life score changes of these domains and the overall instrument. Our study shows that the QLICP-GM has good validity, reliability, responsiveness, and can be used as the general module for cancer patients in China. PMID- 17724722 TI - Circulating human papillomavirus type 16 specific T-cells are associated with HLA Class I expression on tumor cells, but not related to the amount of viral oncogene transcripts. AB - Human papillomavirus (HPV) is a necessary factor in the pathogenesis of cervical cancer. Circulating HPV-specific T-cells responding to the E6 and E7 HPV proteins can be detected only in half of cervical cancer patients. Potential explanations for the absence of this response are lack of sufficient amounts of antigen to activate the immune response or local immune escape mechanisms. We studied the relationship between HPV 16 E6/E7 oncogene mRNA expression, human leukocyte antigen (HLA) expression on tumor cells and the presence of circulating E6- and E7-specific T-cell responses in cervical cancer patients. The amount of antigen was assessed by HPV E6/E7 mRNA expression levels measured by quantitative polymerase chain reaction. HLA Class I and Class II expression on tumor cells was analyzed by immunohistochemistry. A proliferative HPV-specific T-cell response was detected in 15/29 patients. The amount of HPV E6/E7 mRNA was not related to the presence of immune response. HLA Class I expression was downregulated in 19 patients and completely lost in 7 patients. HLA Class II expression was upregulated in 18 patients. HLA Class I expression on tumor cells showed a strong correlation with immunity (p = 0.001). Explicitly, all patients with complete HLA loss lacked HPV specific T-cell responses. The presence of circulating HPV specific T-cells might reflect ongoing antitumor response that is sustained by CD8+ T-cells killing HLA Class I positive cancer cells. We hypothesize that HLA Class I expression status on tumor cells might as well influence the response to HPV E6/E7 directed immunotherapy. PMID- 17724723 TI - HPV genotypes in CIN 2-3 lesions and cervical cancer: a population-based study. AB - The distribution of human papillomavirus (HPV) varies between countries and continents leading to different effectiveness of upcoming prophylactic HPV vaccines. This study analyses the HPV distribution in CIN 2-3, recurrent CIN 2-3 and cervical cancer in Iceland. About 80% of incident cases with CIN 2-3 lesions in 1990 and 1999, 99% of cancer cases in 1990-1994 and 1999-2003, and cases with recurrent CIN 2-3 after conization in 1990 were tested with PCR analysis for the presence of 12 oncogenic HPV types. About 95% of the CIN 2-3 and 92% of the cancer cases tested positive for the included HPV types. HPV 16 was the most frequent type followed by HPV 33, 31, 52, 35, 18, 58, 56, 39, 45, 59 in CIN 2-3 and by HPV 18, 33 45, 31, 39, 52, 35, 51, 56 in cancer. HPV 16 and 18 were associated with a significantly increased cancer risk and HPV 52 and 31 with decreased cancer risk compared to the risk of CIN 3. The HPV distribution differed between histological cancer types, stages and age groups. The number of HPV types was not a significant predictor of cancer. Oncogenic HPV types were found in all persistent or recurrent CIN 2-3 disease after conization. Vaccination against HPV 16/18 is estimated to achieve a minimum 40% reduced rate of CIN 2-3 and a minimum 60% reduced cancer rate. This rate could, however, be increased to 95% and 92% respectively by including all the 12 HPV types tested for in this study. PMID- 17724724 TI - Acne and risk of prostate cancer. AB - In a recent study, prostatectomy specimens from which Propionibacterium acnes was cultured were more likely to have inflammation than culture-negative specimens or specimens positive for other bacteria, leading the authors to hypothesize that P. acnes-mediated inflammation may contribute to prostate carcinogenesis. To indirectly explore associations between P. acnes and prostate cancer, we investigated severe acne, as measured by tetracycline use for 4 or more years, in relation to incident prostate cancer in the Health Professionals Follow-up Study. On the 1992 follow-up questionnaire, participants were asked whether they had ever used "tetracycline for at least 2 months at a time (e.g., for acne or other reason)" and their duration of use. Prostate cancer diagnoses were ascertained on each subsequent biennial questionnaire and confirmed by medical record review. Between 1992 and 2002, 2,147 cases of prostate cancer were reported among 34,629 eligible participants. Men who used tetracycline for 4 or more years had a significantly higher risk of prostate cancer (16 cases, 1,569 person-years) than men who did not use tetracycline (2,071 cases, 304,822 person-years, multivariable-adjusted RR = 1.70, 95% CI: 1.03-2.80). Although intriguing, this finding should be viewed cautiously because of the small number of exposed cases, indirect assessment of severe acne, and complex etiology of acne, which is not limited to P. acnes infection. Therefore, additional biologic and epidemiologic studies are necessary to determine and elucidate the possible role of P. acnes infection in prostate carcinogenesis. PMID- 17724726 TI - Impact of remission induction chemotherapy on survival in older adults with acute myeloid leukemia. AB - BACKGROUND: Significant controversy surrounds the use of remission induction chemotherapy (IC) in older adults with acute myeloid leukemia (AML). Earlier clinical trials have yielded conflicting results and possibly a minor survival benefit, often offset by a longer hospitalization time. METHODS: To evaluate the role of IC in patients with AML, a case control study of patients 60 years or older treated at the Cleveland Clinic Taussig Cancer Center between 1997 and 2005 was conducted. Forty-four patients who did not receive IC were matched by a propensity analysis to 138 patients who received an anthracycline-based regimen. RESULTS: The unadjusted median survival of patients who did not receive IC was 53 days, compared with 197 days (P < .001) for those who did. After further adjusting for age, gender, race, leukocyte count at presentation, AML cytogenetics, history of prior hematologic disorder, and assessing for comorbidities, not receiving IC was still associated with worse survival (hazards ratio of 1.88; 95% confidence interval, 1.15-3.05 [P = .01]). Additional predictors of poor outcomes in older adults with AML included higher leukocyte count at presentation, poor-risk cytogenetics, and African-American race (compared with Caucasians). CONCLUSIONS: The study suggests improved outcomes in older adults with AML who undergo remission induction therapy. PMID- 17724727 TI - Preventing pain during office biopsy of the prostate: a single center, prospective, double-blind, 3-arm, parallel group, randomized clinical trial. AB - BACKGROUND: A prospective, double-blind, 3-arm, parallel group, randomized clinical trial was performed to compare 3 anesthetic techniques for preventing pain during prostate biopsy. METHODS: A total of 243 men undergoing a 12-core prostate biopsy were randomized to 1 of 3 anesthetic methods: 1) seminal vesical prostatic base blockade, 2) intraprostatic blockade, and 3) apical-rectal blockade. Pain was estimated with the 10-point visual analog scale. Multivariate logistic regression evaluated factors predictive of pain. The Kruskal-Wallis test analyzed overall group comparisons and the Steel-Dwass test assessed between group comparisons in pain scores. Proportional odds ordinal logistic regression quantified the ability of covariates and treatment arms to predict biopsy pain. These values are presented as odds ratios with confidence intervals (OR, 95% CI). RESULTS: From November 2005 to June 2006, 81 men were randomized to 3 study arms. Lidocaine administration was the most painful element of the procedure, while probe insertion was the least. Apical biopsies were routinely more painful than mid-gland biopsies, which were more painful than base biopsies. The apical-rectal blockade was the most painful to administer, but has lasting effects and led to better pain control than the prostatic base-seminal vesicle blockade. Similarly, the intraprostatic blockade was more effective than the prostatic base-seminal vesicle blockade. Besides pain reported at the time of anesthetic injection, no difference was identified between the intraprostatic and apical-rectal blockades. CONCLUSIONS: Mid and apical biopsies of the prostate are more painful than base biopsies. The seminal vesicle-prostatic base blockade is less effective than intraprostatic and apical-rectal blockade at controlling pain. PMID- 17724725 TI - S-adenosyl L-methionine inhibits azoxymethane-induced colonic aberrant crypt foci in F344 rats and suppresses human colon cancer Caco-2 cell growth in 3D culture. AB - S-adenosyl L-methionine (SAM) is a universal methyl group donor to various intermediary metabolites, hormones, proteins, neurotransmitters, phospholipids and nucleic acids. Deficiency of folate, which plays a role in the synthesis of SAM leads to increased risk for colon cancer. This study tested the effectiveness of SAM supplementation in protecting against azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats. We also tested the effect of SAM on cyclooxygenase-2 (COX-2) in a macrophage cell line. Further, we developed a 3-D culture model using Caco-2 cells to test the effect of SAM on tumor spheroid size and number. Groups of rats were given the experimental diet containing either 0-, 400- or 800-ppm SAM, 1 week before the first AOM injection and continued until 8 weeks. In the control group, AOM produced a substantial number of aberrant crypt foci (ACF) (96 +/- 8). Dietary administration of SAM significantly reduced the number of total ACF (400 ppm SAM, 68 +/- 7.3, p < 0.01 and 800 ppm SAM, 57 +/- 7.1, p < 0.001). SAM significantly decreased AOM-induced colonic multicrypt foci in a dose-dependent manner. Suppression of Lipopolysaccharide (LPS) induced COX-2 protein expression was observed in a RAW264.7 cell line. We established growth of Caco-2 cells as spheroids, in a 3D matrix of collagen and matrigel. Treatment with SAM decreased both size and number of spheroids in a dose-dependent manner (p < 0.0001). These observations demonstrate for the first time that SAM can reduce the occurrence of ACF in AOM treated male F344 rats and suppress formation of human tumor spheroids and expression of COX-2. PMID- 17724728 TI - Independent predictors of cancer-specific survival in transitional cell carcinoma of the upper urinary tract: multi-institutional dataset from 3 European centers. AB - BACKGROUND: The objective of the current study was to identify variables that were predictive of cancer-specific survival in patients with nonmetastatic transitional cell carcinoma of the upper urinary tract (UUT-TCC). METHODS: Clinical and pathologic data from 269 patients who underwent nephroureterectomy for UUT-TCC from 1989 to 2005 in 3 urologic European centers were collected retrospectively. Log-rank tests and Cox proportional-hazards regression models were used for univariate and multivariate analyses. RESULTS: Two hundred fifty patients underwent nephroureterectomy, and 19 patients underwent concomitant cystectomy for synchronous muscle-invasive bladder cancer. The median follow-up of the whole cohort was 34 months, and the median follow-up of the patients who remained alive and disease-free was 52 months. At follow-up, 57 cancer-related deaths (21.2%) were censored, and 169 patients (62.8%) were alive and disease free. On univariate analysis, a history of previous bladder cancer, pathologic stage of the primary tumor and lymph nodes, tumor grade, the presence of lymphovascular invasion, tumor site, synchronous muscle-invasive bladder TCC, and tumor multifocality were associated with cancer-specific survival probabilities. On multivariate analysis, pathologic stage of the primary tumor and lymph nodes, tumor multifocality within the UUT, synchronous muscle-invasive bladder TCC, and a history of bladder TCC before the diagnosis of UUT-TCC were independent predictors of cancer-specific survival probabilities. CONCLUSIONS: In a multi institutional dataset of patients who had undergone nephroureterectomy for UUT TCC, the current results indicated that pathologic stage of the primary tumor and lymph nodes, a history of prior bladder TCC, the presence of synchronous muscle invasive bladder cancer, and tumor multifocality within the UUT were independent predictors of cancer-specific survival probabilities. PMID- 17724729 TI - Automated docking to explore subsite binding by glycoside hydrolase family 6 cellobiohydrolases and endoglucanases. AB - Cellooligosaccharides were computationally docked using AutoDock into the active sites of the glycoside hydrolase Family 6 enzymes Hypocrea jecorina (formerly Trichoderma reesei) cellobiohydrolase and Thermobifida fusca endoglucanase. Subsite -2 exerts the greatest intermolecular energy in binding beta-glucosyl residues, with energies progressively decreasing to either side. Cumulative forces imparting processivity exerted by these two enzymes are significantly less than by the equivalent glycoside hydrolase Family 7 enzymes studied previously. Putative subsites -4, -3, +3, and +4 exist in H. jecorina cellobiohydrolase, along with putative subsites -4, -3, and +3 in T. fusca endoglucanase, but they are less important than subsites -2, -1, +1, and +2. In general, binding adds 3-7 kcal/mol to ligand intramolecular energies because of twisting of scissile glycosidic bonds. Distortion of beta-glucosyl residues to the (2)S(O) conformation by binding in subsite -1 adds approximately 7 kcal/mol to substrate intramolecular energies. PMID- 17724730 TI - Repair of large full-thickness articular cartilage defects by transplantation of autologous uncultured bone-marrow-derived mononuclear cells. AB - The objective of this study was to investigate the feasibility of autologous uncultured bone marrow-derived mononuclear cell transplantation in large full thickness cartilage regeneration. After fixing with a hinged external fixator, the entire surface of the left tibial plateau was resected and large full thickness cartilage defects were formed in 48 rabbits. Animals were divided into four groups: autologous uncultured bone marrow-derived mononuclear cells with fibrin gel (BMC), autologous uncultured peripheral blood-derived mononuclear cells with fibrin gel (PBC), fibrin gel alone (GEL), or nothing (CON) transplanted to the articular cavity 7 days after the operation. The rabbits were killed 8 or 12 weeks after the operation. The repair of defects was investigated histologically and scored using a histological and histochemical grading scale that was modified from the International Cartilage Repair Society Visual Histological Assessment Scale. To evaluate the regenerated cartilage, we also morphometrically measured the staining area positive for Safranin-O or type II collagen and calculated the percentages of the positive staining areas with respect to the regenerated soft tissue area. Histological findings showed that the BMC group had superior cartilage repair compared with the other groups, and that the PBC and CON group showed better cartilage repair than did the GEL group. Histological scores and morphometrical measurements also showed the same results quantitively. The transplantation of autologous uncultured bone marrow-derived mononuclear cells contributes to articular cartilage repair. The easy and safe method used in this study is potentially viable for clinical application. PMID- 17724731 TI - Tfap2 transcription factors in zebrafish neural crest development and ectodermal evolution. AB - Transcription factor AP2 (Tfap2) genes play essential roles in development of the epidermis and migratory cells of the neural crest (NC) in vertebrate embryos. These transcriptional activators are among the earliest genes expressed in the ectoderm and specify fates within the epidermis/crest through both direct and indirect mechanisms. The Tfap2 family arose from a single ancestral gene in a chordate ancestor that underwent gene duplication to give up to five family members in living vertebrates. This coincided with the acquisition of important roles in NC development by Tfap2 genes suggesting that this gene family was important in ectodermal evolution and possibly in the origin of NC. Here, we show that a zebrafish tfap2c is expressed in the nonneural ectoderm during early development and functions redundantly with tfap2a in NC specification. In zebrafish embryos depleted of both tfap2a and tfap2c, NC cells are virtually eliminated. Cell transplantation experiments indicate that tfap2c functions cell autonomously in NC specification. Cells of the enveloping layer, which forms a temporary skin layer surrounding the ectoderm, also fail to differentiate or to express appropriate keratins in tfap2c deficient embryos. The role of Tfap2 genes in epidermal and NC development is considered here in the broader context of ectodermal evolution. Distinct, tissue-specific functions for Tfap2 genes in different vertebrates may reflect subfunctionalisation of an ancestral gene that consequently led to the gain of novel roles for different subfamily members in patterning the epidermis and NC. PMID- 17724732 TI - Effects of gamma irradiation on osteoinduction associated with demineralized bone matrix. AB - Gamma irradiation is frequently used to sterilize implanted devices but has limitations when used on biologically active materials and composites. In this study, we have evaluated the changes of biological activity of demineralized bone matrix (DBM) in the dry state and in the presence of aqueous and non-aqueous carriers while exposed to various levels of ionizing radiation. The activity of DBM in the dry state remains relatively stable with only a small loss of activity. Composites of DBM with a carrier such as lecithin, to which no water has been added, lose activity at approximately the same rate as DBM in the anhydrous form. In composites that contain water, the loss of activity occurs even at much lower levels of radiation exposure. Gamma irradiation does not change cell attachment to the DBM matrix but has an influence on both stem cell and osteoprecursor cell proliferation rates. Because of the limitations imposed by radiation, it seems most practical to handle DBM aseptically throughout the procedures of compositing pastes, putties, or suspensions, and only if necessary exposing the inert excipients to radiation sterilization prior to mixing. PMID- 17724733 TI - In vitro benzo[a]pyrene diol epoxide-induced DNA damage and chromosomal aberrations in primary lymphocytes, smoking, and risk of squamous cell carcinoma of the head and neck. AB - Cigarette smoking is a major risk factor for squamous cell carcinoma of the head and neck (SCCHN), but only a fraction of those exposed to cigarette smoke develops SCCHN, suggesting variation in individual susceptibility. Tobacco smoke contains a number of carcinogens that cause various kinds of damage to DNA. In this study, we simultaneously measured benzo[a]pyrene diol epoxide-induced DNA damage and chromosomal aberrations by the comet assay and the mutagen sensitivity assay, respectively, in cultured primary lymphocytes from newly recruited 123 patients with SCCHN and 136 age- and sex-matched controls. Using the control median as the cut-off, the elevated risk of SCCHN was 2.35 (95% CI, 1.37-4.03), 2.28 (95% CI, 1.34-3.98) and 3.25 (95% CI, 1.85-5.07) for high levels of tail extension, tail length and oliver tail moment of the comet assay, respectively, and 1.75 (95% CI, 1.04-2.94) for high levels of chromosomal aberrations of the mutagen sensitivity assay. The effects of these 2 types of measurements were additive; subjects with high levels of both DNA damage and chromosomal aberrations had a 4.77-fold increased risk (95% CI, 2.73-8.36) of SCCHN. Cigarette smoking further elevated this risk to more than 20-fold (OR 23.6; 95% CI, 8.92-62.3). These data support our previous finding that suboptimal repair contributed to susceptibility to SCCHN and the new data further suggests a possible gene-environment interaction that may play an important role in the etiology of SCCHN. Further validation studies are warranted. PMID- 17724734 TI - Does the patient's position influence the detection of detrusor overactivity? AB - AIMS: The demonstration of preoperative detrusor overactivity (DO) with associated overactive bladder symptoms (OAB) is known to have an adverse effect on surgery performed for stress incontinence or for prostatic obstruction. The purpose of this review is to examine the best position, when filling the bladder during urodynamics, to demonstrate detrusor overactivity and reproduce the OAB symptoms, when the demonstration of DO might be important. MATERIALS AND METHODS: MEDLINE and PUBMED literature searches were performed, spanning the period from 1956 to August 2005 using the keywords "detrusor overactivity" or "detrusor instability" combined with "posture or position or standing or sitting" and "urodynamics." Other studies were identified by reviewing secondary references in the original citations. RESULTS: Sixteen studies looked at the effect of position on the detection rate of DO. There is good consistency between the studies analyzed. All but two [Ramsden et al., Br J Urol 49:633-9, 1977; Choe et al., J Urol 161:1541-4, 1999] showed a clear effect, with an increase in DO when the patient is filled in the vertical position or is asked to sit or stand, with a full bladder, after being filled supine. Performing the urodynamics (UDS) in the supine position would have missed a large proportion of DO diagnoses ranging from 33% to 100%. CONCLUSIONS: This review confirms that the patient's position is a significant variable during urodynamics and that supine cystometry will fail to detect a significant percentage of patients with DO. We suggest that all patients should be filled sitting or standing, unless physically disabled. It seems desirable for the International Continence Society (ICS) to extend its "Good urodynamic practice guideline" [Schafer et al., Neurourol Urodyn 21:261-74, 2002] to cover this important issue. PMID- 17724735 TI - Altered distribution of interstitial cells in the guinea pig bladder following bladder outlet obstruction. AB - AIMS: We investigated the effects of bladder outlet obstruction (BOO) on the distribution of interstitial cells (ICs) in the guinea-pig bladder. METHODS: Bladder overactivity of BOO animals was validated with urodynamic studies. Immunohistochemical analyses for Kit and vimentin as markers for ICs were performed on both BOO and control bladders. Morphological and functional properties of detrusor smooth muscle (DSM) were examined with alpha-smooth muscle actin staining and intracellular recording, respectively. Electron microscopy was also carried out to characterize ultrastructural morphology of ICs. RESULTS: Two weeks after surgery, BOO animals showed an increased voiding frequency and a reduced voiding volume. Filling cystometry demonstrated a frequent incidence of non-voiding contractions, a reduced interval between voiding contractions and an increased voiding pressure in BOO bladders. In BOO bladders, the thickness of suburothelial and subserosal connective tissue layers was increased, whilst that of detrusor smooth muscle (DSM) layer was less affected. Population of Kit or vimentin immunoreactive ICs was increased in subserosal layers, and their distribution was altered in suburotherial layer in BOO bladders. Neither alpha actin immunoreactivity nor spontaneous electrical activity of DSM was altered in BOO bladders. ICs were characterized by their numerous mitochondria and caveolae, and had a close contact with each other and with neighboring DSM or nerves. CONCLUSIONS: These results demonstrated the increased population of ICs in the BOO guinea-pig model for the first time, and suggest that the altered distribution of ICs may contribute to the pathophysiology of bladder overactivity. PMID- 17724736 TI - Effect of random interpulse interval modulation on neuromuscular fatigue. AB - Neuromuscular endurance during electrical stimulation may be enhanced if naturally occurring motor unit firing patterns are used. Variability in the interpulse interval (IPI) distribution may enable brief periods of rest and optimization of force output. Nine individuals participated in three 3-minute fatigue protocols of the thenar muscles elicited by supramaximal stimulation of the median nerve. All protocols consisted of a mean IPI of 33.3 ms and differed only in the type of IPI modulation, which was constant (0%), random (+/-20%), or ramped from 0% to +/-20%. M-wave amplitude declined following all protocols and the reduction was smallest following the ramp protocol. There was no significant difference among the starting or final forces or between the overall force-time integrals for the three protocols. Thus, IPI variability did not improve endurance time during electrical stimulation and the M-wave amplitude was not a reliable indicator of muscle force output. PMID- 17724737 TI - Nodular-type muscle sarcoidosis developing after a dog bite. AB - We report a 46-year-old woman who experienced swelling of the right thigh around the wound caused by a dog bite. Physical findings, laboratory findings, imaging studies, and muscle biopsy showed that this was nodular-type muscle sarcoidosis. This is an unusual case of sarcoidosis, and the possibility is discussed that a dog bite may serve as a trauma to trigger sarcoidosis in genetically predisposed individuals. PMID- 17724738 TI - Disodium cromoglycate protects dystrophin-deficient muscle fibers from leakiness. AB - In dystrophin-deficient fibers of mdx mice and in Duchenne dystrophy, the lack of dystrophin leads to sarcolemma breakdown and muscle degeneration. We verified that cromolyn, a mast-cell stabilizer agent, stabilized dystrophic muscle fibers using Evans blue dye as a marker of sarcolemma leakiness. Mdx mice (n=8; 14 days of age) received daily intraperitoneal injections of cromolyn (50 mg/kg body weight) for 15 days. Untreated mdx mice (n=8) were injected with saline. Cryostat cross-sections of the sternomastoid, tibialis anterior, and diaphragm muscles were stained with hematoxylin and eosin. Cromolyn dramatically reduced Evans blue dye-positive fibers in all muscles (P<0.05; Student's t-test) and led to a significant increase in the percentage of fibers with peripheral nuclei. This study supports the protective effects of cromolyn in dystrophic muscles and further indicates its action against muscle fiber leakiness in muscles that are differently affected by the lack of dystrophin. PMID- 17724739 TI - Augmented gp130-mediated cytokine signalling accompanies human gastric cancer progression. AB - H. pylori infection accounts for most cases of gastric cancer, but the initiating events remain unclear. The principal H. pylori pathogenicity-associated CagA protein disrupts intracellular SHP-2 signalling pathways including those used by the IL-6 family cytokines, IL-6 and IL-11. Imbalanced IL-6 family cytokine signalling in the gp130(757FF) mouse model of gastric cancer arising from hyperactivation of oncogenic STAT3 after altered SHP-2 : ERK1/2 signalling produces dysplastic antral tumours preceded by gastritis and metaplasia. In a cohort of patient gastric biopsies with known H. pylori and CagA status, we investigated whether (i) STAT3 and ERK1/2 activation is altered in H. pylori dependent gastritis; (ii) these profiles are more pronounced in CagA+ H. pylori infection; and (iii) the expression of pro-inflammatory cytokines that activate STAT3 and ERK 1/2 pathways is associated with progression to gastric cancer. IL 6, IL-11, and activated STAT3 and ERK1/2 were quantified in antral biopsies from gastritic stomach, metaplastic tissue, and resected gastric cancer tissues. We observed significantly increased STAT3 and ERK1/2 activation (p = 0.001) in H. pylori-dependent gastritis, which was further enhanced in the presence of CagA+ H. pylori strains. Of known gastric ligands that drive STAT3 activation, IL-6 expression was increased after H. pylori infection and both IL-6 and IL-11 were strongly up-regulated in the gastric cancer biopsies. This suggests a mechanism by which IL-11 drives STAT3 activation and proliferation during gastric cancer progression. We addressed this using an in vitro approach, demonstrating that recombinant human IL-11 activates STAT3 and concomitantly increases proliferation of MKN28 gastric epithelial cells. In summary, we show increased STAT3 and ERK1/2 activation in H. pylori-dependent gastritis that is likely driven in an IL-6 dependent fashion. IL-11 expression is associated with adenocarcinoma development, but not gastritic lesions, and we identify a novel mechanism for IL 11 as a potent inducer of proliferation in the human gastric cancer setting. PMID- 17724740 TI - Adverse effects during the treatment with pegylated interferon and ribavirin in children with chronic hepatitis C. AB - PURPOSE: Administration of pegylated interferon-alpha (IFN-alpha) and ribavirin in adults with chronic hepatitis C (CHC) is a recommended therapeutic standard. Nevertheless, this therapeutic regimen rises numerous controversies. The aim of this study was to analyze adverse effects during the treatment with pegylated IFN alpha and ribavirin in children with CHC. METHODS: Study group comprised 30 children with CHC, age 8-19 years (mean 13,6 years), 9 girls and 21 boys. All patients were administered two medication therapy with pegylated IFN-alpha-2b in the dose of 1.5 microg/kg of body weight 1x/week subcutaneously and daily oral ribavirin 15 mg/kg of bodyweight for 48 weeks. Blood samples were taken at baseline and every 4 weeks during the whole treatment and 24 weeks of follow-up period. Panel of test included: cellular blood count and smear, ALT activity, bilirubin level. Patients complaints were noticed during every visit. Thyroid hormones and antibodies were checked every 3 months. Children were divided into group A that responded to treatment and group B-nonresponders. RESULTS: Abnormalities in laboratory tests (white blood cells, neutrophils, haemoglobin) were observed mainly during first weeks of treatment. Mean bilirubin level and platelets were normal. Mean ALT normalized during the treatment. After 12-16 weeks of the therapy somatic adverse effects decreased significantly. CONCLUSIONS: Administration of pegylated IFN-alpha and ribavirin in children with CHC is related to characteristic adverse effects. Periodical dose reduction was necessary. Although side effects and subjective patient complaints were present, children attended school without difficulties. Constant monitoring is required during the whole treatment. PMID- 17724741 TI - The US drug safety system: role of the pharmaceutical industry. AB - PURPOSE: Despite increasingly strident calls for improved drug safety in the United States, recent events underscore the continuing gap among manufacturers, regulators, patients, and physicians. In the period leading to the recent Institute of Medicine report on the future of drug safety, representatives from industry were given an opportunity to provide input into this report. In light of continuing concerns about drug safety and pending legislation, this original perspective provides an important context. METHODS: This work consolidates the views of representatives of individual pharmaceutical companies; the large industry trade associations, the Pharmaceutical Researchers and Manufacturers of America (PhRMA) and the Biotechnology Industry Association (BIO); and those of the authors with regard to the industry role of drug safety in the United States. RESULTS: To ensure continued protection of the public's health, manufacturers must recognize themselves as critical to ensuring safe products; maintain corporate safety functions separate from marketing functions; provide oversight by a senior medical executive; engage in structured epidemiological research, risk assessment, and risk communication; and mandate the formation and maintenance of an internal, interdisciplinary, senior level safety council. CONCLUSIONS: The importance of aggressive and accountable drug safety will only become more salient as the public and their elected representatives demand better accountability from industry. Individual corporations now have the opportunity to move first to counter perceptions of profit over safety and to ensure that their business practices adequately protect the public's health. PMID- 17724742 TI - Social inequality in premature mortality among Polish urban adults during economic transition. AB - Rates of premature mortality among adults are important measures of the economic and psychosocial well-being of human populations. In many countries, such rates are, as a rule, inversely related to the level of attained education. We examined changes in educational group-specific mortality rates among urban adults in Poland during the country's rapid transition in the 1990s from a socialist command economy to a free market system. Two census-based analyses of individual death records of urban dwellers aged 35-64 years were compared. We utilized all records of death, which occurred during the 2-year periods 1988-89 and 2001-02. Population denominators were taken from the censuses of 1988 and 2002. The age specific mortality rates were used to evaluate absolute differences in mortality. To assess relative differences between educational levels, mortality rate ratios (MRRs) with 95% CI (confidence interval) were calculated using Poisson regression. A regular educational gradient in mortality persisted in each 10-year age group throughout the period covered by our data. Moreover, age-specific mortality rates declined steadily in all educational groups, and this decline was most marked in the two oldest age groups (45-54 and 55-64 years). The trend was accompanied by widening of educational differences in mortality as expressed by MRRs. Systemic political transformation in Poland has brought a mixture of beneficial and detrimental effects on the well-being of society. With regard to the changes in rates of premature mortality among adults, the benefits have prevailed, although individuals with the lowest educational level benefited less than those with the highest education. PMID- 17724744 TI - Daily differences in patterns of physical activity among overweight/obese children engaged in a physical activity program. AB - The aim of this study was to compare the physical activity of overweight/obese children during days when they attended a physical activity program, and days when they did not. This is a cross-sectional intervention study of daily physical activity. The participants were referred by family, doctors, or hospital pediatricians to take part in a 10-month interdisciplinary, outpatient obesity intervention program for children. The subjects included 41 overweight and obese children aged 8-16 years, 19 boys (46%) and 22 girls (54%); BMI: 25.7 + 3.3 kg m( 2). The MTI Actigraph was used as an objective measure of daily physical activity over seven consecutive days. Physical activity program days presented a significantly higher percentage of time (4.68%) spent in moderate-to-vigorous activity compared with no physical activity program days (3.16%) and weekend (2.7%). The results of this study suggest that a physical activity program can help increasing daily physical activity in obese children, with a special focus on MVPA level. Our data point that obese children are less active at weekend than during weekdays. PMID- 17724746 TI - Long lasting pure freezing of gait preceding progressive supranuclear palsy: a clinicopathological study. AB - Primary progressive freezing of gait (PPFG) is the term used to designate an uncommon condition featuring freezing of gait with frequent falls, without bradykinesia, rigidity or tremor, and unresponsive to levodopa. There are very few pathological reports of patients with PPFG in the literature. We report on 2 patients (one with pathological confirmation) diagnosed initially as PPFG and evolving into clinically defined progressive supranuclear palsy (PSP) more than 10 years after onset of symptoms. These 2 cases suggest that PPFG can represent the initial manifestation of a neurodegenerative disease, such as PSP, rather than a differentiated nosological entity. PMID- 17724745 TI - EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma. AB - The molecular hallmark of angiomatoid fibrous histiocytoma (AFH) is not well defined, with only six cases with specific gene fusions reported to date, consisting of either FUS-ATF1 or EWSR1-ATF1. To address this, we investigated the presence of FUS-ATF1, EWSR1-ATF1, and the highly related EWSR1-CREB1 fusion in a group of nine AFHs. All cases were subjected to RT-PCR for EWSR1-ATF1 and EWSR1 CREB1. FISH for EWSR1 and FUS rearrangements was performed in most cases. Transcriptional profiling was performed in three tumors and their gene expression was compared to five clear cell sarcomas expressing either the EWSR1-ATF1 or EWSR1-CREB1 fusion. By RT-PCR, eight out of nine tumors showed the presence of the EWSR1-CREB1 fusion, while one had an EWSR1-ATF1 transcript. FISH showed evidence of EWSR1 rearrangement in seven out of eight cases. Karyotypic analysis performed in one tumor showed a t(2;22)(q33;q12). High transcript levels were noted for TFE3 in AFH tumors, while overexpression of genes involved in melanogenesis, such as MITF, GP100, and MET was noted in somatic clear cell sarcomas. We report for the first time the presence of EWSR1-CREB1 in AFH, which now appears to be the most frequent gene fusion in this tumor. EWSR1-CREB1 is a novel translocation recently described in clear cell sarcoma of the GI tract. EWSR1-ATF1, identified in some AFH cases, is the most common genetic abnormality in soft tissue clear cell sarcoma. Thus, identical fusions involving ATF1 and CREB1 are found in two distinct sarcomas, which may be able to transform two different types of mesenchymal precursor cells, unlike most other sarcoma gene fusions. PMID- 17724747 TI - Prospective comparative study on cost-effectiveness of subthalamic stimulation and best medical treatment in advanced Parkinson's disease. AB - This is an open, prospective, longitudinal study designed to compare two cohorts of patients with advanced Parkinson's disease during 1 year, one undergoing bilateral subthalamic stimulation (STN-DBS) and the other receiving the best medical treatment (BMT), with respect to the clinical effects observed and the medical expenses produced. Assessments were done by using clinical measures and a generic health related quality of life scale. A questionnaire was used to collect direct healthcare resources. As a measure of cost-effectiveness, we calculated life years gained adjusted by health-related quality of life (QALY) and the incremental cost-effectiveness ratio (ICER). Clinical and demographic variables of both groups were comparable at baseline. Total UPDRS scores improved from 50.5 +/- 3.6 to 28.5 +/- 3.8 in STN-DBS patients and worsened from 44.3 +/- 3.3 to 54.2 +/- 4 in the control group. Pharmacological costs in the operated patients were 3,799 +/- 940 euro, while in the BMT group the costs were 13,208 +/- 4,966 euro. Other medical costs were 1,280 +/- 720 euro in the STN-DBS group and 4,017 +/- 2,962 euro in BMT patients. Nondirect medical costs were 4,079 +/- 1,289 in operated patients and 2,787 +/- 1,209 euro in the BMT group. Mean QALYs were 0.7611 +/- 0.03 in STN-DBS and 0.5401 +/- 0.06 in BMT patients. In STN-DBS patients, the ICER needed to obtain an improvement of one point in the total UPDRS score was of 239.8 euro and the ICER/QALY was of 34,389 euro. Cost effectiveness parameters were mostly related to the degree of clinical improvement and the reduction of pharmacological costs after STN-DBS. An ICER of 34,389 euro/QALY is within appropriate limits to consider subthalamic stimulation as an efficient therapy. PMID- 17724748 TI - Pill counts, self reports, and electronic monitoring -- which is most informative in the study of therapy adherence in Parkinson's disease? PMID- 17724751 TI - Rational design of MOFs constructed from modified aromatic amino acids. AB - Three Phe and Tyr derivatives, 2-amino-3-(4-aminophenyl)-propionic acid (AAP), 3E [5-(2-amino-2-carboxyethyl)-2-methoxyphenyl]-acrylic acid (AMPA) and 3-(4 aminophenyl)-2-(carboxymethyl-amino)-propionic acid (ACP) have been chosen as the ligands to construct four kinds of novel metal-organic frameworks (MOFs) (five structures). These structures are, [Cd(II){(R)-AAP}(Py)(H(2)O)](ClO(4)), (R)-1; [Cd(II){(S)-AAP}(H(2)O)(2)](ClO(4)), (S)-2; [Zn(2) (II){(R,S)-AMPA}(H(2)O)], (R,S)-3; [Zn(2) (II){(R)-ACP}(Py)(3)](ClO(4))(2), (R)-4; and the inversion twin of (R)-1. Rational design to adjust the "depth" and the "width" of ligands can mediate the size and the shape of the grids of these 2D layers. Additionally, among these compounds, three pure chiral coordination polymers are obtained, owing to the inducement of chirality by the modified amino acids. This property makes them potential NLO materials. PMID- 17724756 TI - The lipase-catalyzed hydrolysis of lutein diesters in non-aqueous media is favored at extremely low water activities. AB - The enzymatic hydrolysis of a mixture of lutein diesters from Marigold flower (Tagetes erecta) was performed both in organic solvents and supercritical CO(2) (SC-CO(2)) using two commercial lipases: lipase B from Candida antarctica (Novozym 435) and the lipase from Mucor miehei (Lipozyme RM IM). Both lipases showed an unexpected dependence of initial reaction rate with the initial water activity (a(wi)) in hexane, with the highest rates of hydrolysis taking place at the lowest a(wi) of the biocatalyst particles. The same result was observed using isooctane, toluene, or SC-CO(2). It is proposed that an increase in a(wi) generates a hydrophilic microenvironment that prevents efficient partitioning of the highly hydrophobic lutein diesters to the enzyme. The critical role of water in this system has not been reported for other hydrolytic reactions in low water media. Calculations of water available for hydrolysis from isotherm analysis, Karl-Fischer titration, and substrate conversion at a(wi) = 0.13, indicate that the extent of reaction is not limited by the amount of available water. Accordingly, the enzyme that holds the largest amount of water after prehydration at the same a(wi) (0.13) will yield the greatest substrate conversion and concentration of the free lutein product. The highest conversion occurred in SC CO(2), which opens up new opportunities to develop a combined extraction-reaction process for the environmentally benign synthesis of lutein, an important nutraceutical compound. PMID- 17724757 TI - Combined removal of sulfur compounds and nitrate by autotrophic denitrification in bioaugmented activated sludge system. AB - An autotrophic denitrification process using reduced sulfur compounds (thiosulfate and sulfide) as electron donor in an activated sludge system is proposed as an efficient and cost effective alternative to conventional heterotrophic denitrification for inorganic (or with low C/N ratio) wastewaters and for simultaneous removal of sulfide or thiosulfate and nitrate. A suspended culture of sulfur-utilizing denitrifying bacteria was fast and efficiently established by bio-augmentation of activated sludge with Thiobacillus denitrificans. The stoichiometry of the process and the key factors, i.e. N/S ratio, that enable combined sulfide and nitrogen removal, were determined. An optimum N/S ratio of 1 (100% nitrate removal without nitrite formation and low thiosulfate concentrations in the effluent) has been obtained during reactor operation with thiosulfate at a nitrate loading rate (NLR) of 17.18 mmol N L(-1) d(-1). Complete nitrate and sulfide removal was achieved during reactor operation with sulfide at a NLR of 7.96 mmol N L(-1) d(-1) and at N/S ratio between 0.8 and 0.9, with oxidation of sulfide to sulfate. Complete nitrate removal while working at nitrate limiting conditions could be achieved by sulfide oxidation with low amounts of oxygen present in the influent, which kept the sulfide concentration below inhibitory levels. PMID- 17724759 TI - What is the biological relevance of the specific bond properties revealed by single-molecule studies? AB - During the last decade, many authors took advantage of new methodologies based on atomic force microscopy (AFM), biomembrane force probes (BFPs), laminar flow chambers or optical traps to study at the single-molecule level the formation and dissociation of bonds between receptors and ligands attached to surfaces. Experiments provided a wealth of data revealing the complexity of bond response to mechanical forces and the dependence of bond rupture on bond history. These results supported the existence of multiple binding states and/or reaction pathways. Also, single bond studies allowed us to monitor attachments mediated by a few bonds. The aim of this review is to discuss the impact of this new information on our understanding of biological molecules and phenomena. The following points are discussed: (i) which parameters do we need to know in order to predict the behaviour of an encounter between receptors and ligands, (ii) which information is actually yielded by single-molecule studies and (iii) is it possible to relate this information to molecular structure? PMID- 17724760 TI - Protective effect of Amomi semen extract on alloxan-induced pancreatic beta-cell damage. AB - The protective effect of Amomi semen extract (ASE) on alloxan-induced pancreatic beta-cell damage was investigated in HIT T-15 cells, a Syrian hamster pancreatic beta-cell line. Alloxan caused pancreatic beta-cell damage through the generation of reactive oxygen species (ROS), the elevation of cytosolic free Ca2+, DNA fragmentation and the decrease of cellular NAD+ and ATP levels. All these effects of alloxan were significantly prevented by pretreatment with a water-soluble extract of Amomi semen. Pretreatment with ASE in pancreatic islets isolated from mice, also significantly abolished the inhibition of glucose-stimulated insulin secretion by alloxan. The results of this study provide evidence that ASE may have a protective activity on alloxan-induced beta-cell damage, and that the protective effect is primarily due to the inhibition of ROS generation by alloxan. PMID- 17724761 TI - Anticonvulsant activity of Hypoxis hemerocallidea Fisch. & C. A. Mey. (Hypoxidaceae) corm ('African potato') aqueous extract in mice. AB - Extracts of Hypoxis hemerocallidea Fisch. & C. A. Mey. (Hypoxidaceae) corm (popularly known as 'African potato') are extensively used in South African traditional medicines for the treatment, management and/or control of an array of human ailments, including childhood convulsions and epilepsy. This study examined the anticonvulsant activity of the plant's corm aqueous extract (APE, 50-800 mg/kg i.p.) against pentylenetetrazole (PTZ)-, picrotoxin (PCT)- and bicuculline (BCL)-induced seizures in mice. Phenobarbitone and diazepam were used as reference anticonvulsant drugs for comparison. Like the reference antiseizure drugs used, Hypoxis hemerocallidea corm aqueous extract (APE, 100-800 mg/kg i.p.) significantly delayed (p < 0.05-0.001) the onset of, and antagonized, pentylenetetrazole (PTZ)-induced seizures. The plant's corm aqueous extract (APE, 100-800 mg/kg i.p.) also profoundly antagonized picrotoxin (PCT)-induced seizures, but only weakly antagonized bicuculline (BCL)-induced seizures. Although the data obtained in the present study do not provide conclusive evidence, it would appear that 'African potato' aqueous extract (APE) produces its antiseizure effect by enhancing GABAergic neurotransmission and/or action in the brain. The results of this laboratory animal study indicate that APE possesses anticonvulsant activity in the mammalian experimental model used and, therefore, tend to suggest that the herb may be used as a natural supplementary remedy in the management, control and/or treatment of childhood convulsions and epilepsy. In conclusion, the findings of this study indicate that Hypoxis hemerocallidea corm aqueous extract possesses anticonvulsant activity, and thus lend pharmacological credence to the suggested folkloric, anecdotal ethnomedical uses of the herb in the management of childhood convulsions and epilepsy in some rural communities of South Africa. PMID- 17724762 TI - Second trimester prenatal ultrasound and screening for Down syndrome. PMID- 17724763 TI - The antidiabetic activity of total lignan from Fructus Arctii against alloxan induced diabetes in mice and rats. AB - The antidiabetic activity of the total lignan from the plant Fructus Arctii, used in China for the control of diabetes, was investigated in models of alloxan induced diabetic mice and hyperglycemic-hyperlipidemic diabetic rats. The biochemical parameters studied were: blood glucose, glucose tolerance, serum insulin, serum triglycerides, total cholesterol and high density lipoprotein (HDL). Total lignan was given to mice and rats daily for 10 days at doses of 2.0, 1.0, 0.5 g/kg and 1.38, 0.69, 0.35 g/kg respectively. The alloxan-diabetic animals showed significant reductions in plasma glucose, triglycerides and total cholesterol after treatment with the total lignan from the plant Fructus Arctii and glibenclamide (used as standard) compared with the diabetic controls, while the glucose tolerance, serum insulin level and HDL-cholesterol were elevated without the risk of hypoglycemia. In conclusion, the total lignan from the plant Fructus Arctii has been proven to be a safer antidiabetic agent and might help to prevent diabetic complications. It can serve as a good adjuvant in the present armamentarium of antidiabetic drugs. PMID- 17724764 TI - Antiinflammatory activities of Rubus coreanus depend on the degree of fruit ripening. AB - The dried unripe fruit of Rubus coreanus, which is well-known in Korea and referred to as 'Bok-bun-ja', has been employed as a traditional medicine for centuries. This crude drug is utilized in Korea for the management of impotence, spermatorrhea, enuresis, asthma and allergic diseases. The principal objective of the present study was to conduct a comparison of the antiinflammatory effects of ethanol extracts of the unripe (URCE), half-ripened (HRCE) and ripe fruits (RCE) of Rubus coreanus. URCE and HRCE were found to reduce the production of nitric oxide (NO) and prostaglandin E2 (PGE2) as well as pro-inflammatory cytokines, in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages. However, RCE exerted no inhibitory effects against the production of NO and IL-6. The results of the study show that the degree of fruit ripening of Rubus coreanus affects the production of inflammatory mediators such as NO, PGE2 and inflammatory cytokines. PMID- 17724765 TI - Inhibition of non-enzymatic glycation by silk extracts from a Mexican land race and modern inbred lines of maize (Zea mays). AB - Non-enzymatic glycation and the accumulation of advanced glycation end products (AGEs) are associated with various disease states, including complications of diabetes and aging. Secondary metabolites from several plant species are known to inhibit non-enzymatic glycation and the formation of AGEs, including flavonoids found in the style (silk) of Zea mays (maize). Thirteen modern maize inbreds and one land race were tested for in vitro inhibition of non-enzymatic glycation of bovine serum albumin. Many of the tested extracts exhibited inhibitory activity, in particular the newest inbreds, which were bred for resistance to gibberella ear rot (Fusarium graminearum) and common smut (Ustilago maydis). The most active maize genotype (CO441), displaying an IC50 of 9.5 microg/mL, was more effective than aminoguanidine, a known inhibitor of glycation. Zapalote chico, a land race with high maysin content, showed only moderate inhibitory activity compared with the modern maize genotypes. Antiglycation activity was highly correlated with the total phenolic content of silk extracts and mildly correlated with resistance to certain fungal infections. The results identify modern resistant and high phenolic maize inbreds as promising candidates for the development of natural AGE inhibitors for the prevention and treatment of diabetic complications and the degenerative effects of aging. PMID- 17724767 TI - In vitro activity of an essential oil against Leishmania donovani. AB - The in vitro antileishmanial effect of the essential oil from Chenopodium ambrosioides against Leishmania donovani was investigated. The product showed significant activity against promastigotes and amastigotes, with a 50% effective concentration of 4.45 and 5.1 microg/mL, respectively. The essential oil caused an irreversible inhibition of the growth of promastigotes after a treatment with 100 or 10 microg/mL for 1 or 24 h, respectively. The phagocytic activity of the macrophages was preserved at a concentration toxic to the parasite. The essential oil from C. ambrosioides may be a potential candidate drug to development a new agent to combat this parasitic disease. PMID- 17724768 TI - Antibacterial activity of Chamomilla recutita oil extract against Helicobacter pylori. AB - The antibacterial activity of an oil extract of Chamomilla recutita flowers against Helicobacter pylori (H. pylori) was evaluated by the agar dilution method using Colombia agar with 10% sheep blood, an inoculum of McFarland 0.5 and incubation in an anaerobic atmosphere at 37 degrees C for 3 days. The oil extract was prepared by olive oil extraction of Chamomilla recutita flowers using rotary pulsation. The MIC(90) (minimal inhibitory concentration) and MIC(50) were 125 mg/mL and 62.5 mg/mL, respectively. It was shown that the Chamomilla recutita oil extract inhibited the production of urease by H. pylori. In addition, it was found that the morphological and fermentative properties of H. pylori were affected by application of the Chamomilla recutita oil extract. PMID- 17724770 TI - Antifibrotic effects of a herbal combination regimen on hepatic fibrotic rats. AB - Liver fibrosis has been characterized as chronic inflammatory processes involving multiple molecular pathogenetic pathways. This therapeutic study investigated whether a combination regimen of Salvia miltiorrhiza (S), Ligusticum chuanxiong (L) and Glycyrrhiza glabra (G) exerted in vivo antifibrotic effects on rats with hepatic fibrosis. Fibrosis was induced in rats by dimethylnitrosamine (DMN) administration for 4 weeks. Fibrotic rats were randomly assigned to one of the three groups: control, SLG (50 mg/kg) or silymarin (50 mg/kg), each given by gavage twice daily for 3 weeks starting 1 week after DMN injection. The results showed that fibrosis scores of livers from DMN-treated rats with SLG (1.13 +/- 0.13) were significantly reduced in comparison with DMN-treated rats receiving vehicle (1.63 +/- 0.18). Moreover, the hepatic collagen content of DMN rats was significantly reduced by either SLG or silymarin treatment. The double immunohistochemical staining results also showed that alpha-SMA positive cells with NF kappa B nuclear translocation were decreased in the fibrotic livers by SLG and silymarin treatments. The mRNA expression levels of TGF-beta1, alpha-SMA, collagen1 alpha 2, iNOS and ICAM-1 genes were attenuated by SLG and silymarin treatment. The results showed that SLG exerted antifibrotic effects in rats with DMN-induced hepatic fibrosis. PMID- 17724769 TI - Antiplatelet and antithrombotic activity of indole-3-carbinol in vitro and in vivo. AB - Indole-3-carbinol, a natural compound found in cruciferous vegetables, is known to have anticancer activity. In the present study, the antiplatelet and antithrombotic activities of indole-3-carbinol were investigated in vitro and in vivo. Indole-3-carbinol significantly inhibited collagen-induced platelet aggregation in human platelet rich plasma (PRP) in a concentration-dependent manner. Indole-3-carbinol significantly inhibited fibrinogen binding to the platelet surface glycoprotein IIb/IIIa (GP IIb/IIIa) receptor by flow cytometric analysis. In addition, the levels of thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) in collagen stimulated PRP were significantly inhibited in a concentration dependent manner by indole-3-carbinol. Furthermore, indole-3-carbinol dose dependently suppressed the death of mice with pulmonary thrombosis induced by intravenous injection of collagen and epinephrine. These results suggest that indole-3-carbinol can be a potent antithrombotic agent with antiplatelet activity through the inhibition of GP IIb/IIIa receptor and thromboxane B2 formation. PMID- 17724771 TI - Flavonoids from Chinese Viscum coloratum produce cytoprotective effects against ischemic myocardial injuries: inhibitory effect of flavonoids on PAF-induced Ca2+ overload. AB - Viscum coloratum has been used in the indigenous system of medicine for the treatment of various diseases such as myocardial ischemia and arrhythmia. Platelet-activating factor (PAF) is an important player in cardiovascular diseases. The aim of this study was to investigate the protective effects of Viscum coloratum flavonoids (VCF) against ischemic myocardial injuries in vivo and to further investigate its regulatory effect on PAF. Studies were performed in a rat model of myocardial infarction and in isolated myocytes. It was found that VCF relieved myocardial injuries during ischemia. PAF (10(-11) m) significantly increased the intracellular free Ca2+ concentration ([Ca2+]i) and VCF inhibited the changes induced by PAF in single cardiac myocytes. The results suggest that VCF can improve cardiac function and that VCF reduces ischemic myocardial injuries via blocking the signaling pathway of PAF. Therefore, PAF blockers may be candidate drugs for preventing cardiac injuries during ischemia/reperfusion, and subsequently improving cardiac function. PMID- 17724772 TI - Antigenotoxic effect of extract from Cynara cardunculus L. AB - The extract of artichoke Cynara cardunculus L. (CCE) was investigated for its potential antigenotoxic and antioxidant effects using four experimental model systems. In the Saccharomyces cerevisiae mutagenicity/antimutagenicity assay, CCE significantly reduced the frequency of 4-nitroquinoline-N-oxide-induced revertants at the ilv1 locus and mitotic gene convertants at the trp5 locus in the diploid Saccharomyces cerevisiae tester strain D7. In the simultaneous toxicity and clastogenicity/anticlastogenicity assay, it exerted an anticlastogenic effect against N-nitroso-N'-methylurea-induced clastogenicity in the plant species Vicia sativa L. On the contrary, despite CCE not being mutagenic itself, in the preincubation Ames assay with metabolic activation, it significantly increased the mutagenic effect of 2-aminofluorene in the bacterial strain Salmonella typhimurium TA98. In the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay, CCE exhibited considerable antioxidant activity. The SC50 value representing 0.0054% CCE corresponds to an antioxidant activity of 216.8 microm ascorbic acid which was used as a reference compound. Although the mechanism of CCE action still remains to be elucidated, different possible mechanisms are probably involved in the CCE antigenotoxic effects. It could be concluded that CCE is of particular interest as a suitable candidate for an effective chemopreventive agent. PMID- 17724773 TI - Expression of Candida albicans Sfu1 in fission yeast complements the loss of the iron-regulatory transcription factor Fep1 and requires Tup co-repressors. AB - The opportunistic pathogenic yeast Candida albicans contains a gene which encodes a putative member of the iron-regulatory GATA factor protein family. This protein, referred to as suppressor of ferric uptake (Sfu1), has two Cys(2)/Cys(2) type zinc finger domains separated by a conserved Cys-rich region. In Schizosaccharomyces pombe, the GATA-type transcription factor Fe protein 1 (Fep1) represses target gene expression when iron levels exceed those needed by the cell. To ascertain the functional similarity between Sfu1 and Fep1, the C. albicans Sfu1 was expressed in Sz. pombe cells lacking the endogenous fep1(+) gene. We determined that Sfu1 is capable of suppressing iron-related phenotypes of fep1Delta mutant cells. Using a functional SFU1-GFP fusion allele, the Sfu1 protein was localized to the nucleus under both iron-replete and iron-starved conditions. Sfu1 effectively regulated the expression of genes encoding components of the reductive and non-reductive iron transport systems. Furthermore, the iron-responsive regulation mediated by Sfu1 was GATA-dependent. The N-terminal 250 amino acid segment of Sfu1 expressed in and purified from Escherichia coli specifically associated with the hexanucleotide sequence AGATAA in an iron-dependent manner. On the other hand, expression of the full-length C. albicans Sfu1 in Sz. pombe fep1Delta tup11Delta tup12Delta triple mutant cells failed to repress target gene expression under conditions of high iron concentration. Using two-hybrid analysis, we demonstrated that Tup11 and Tup12 physically interacted with Sfu1. Taken together, these results reveal a remarkable functional conservation between Sfu1 from C. albicans and Fep1 from Sz. pombe in their ability to sense excess iron and respond by repressing target gene transcription. PMID- 17724775 TI - Eye drop delivery of nano-polymeric micelle formulated genes with cornea-specific promoters. AB - BACKGROUND: This study evaluates the eye drop delivery of genes with cornea specific promoters, i.e., keratin 12 (K12) and keratocan (Kera3.2) promoters, by non-ionic poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO PPO-PEO) polymeric micelles (PM) to mouse and rabbit eyes, and investigates the underlying mechanisms. METHODS: Three PM-formulated plasmids (pCMV-Lac Z, pK12 Lac Z and pKera3.2-Lac Z) containing the Lac Z gene for beta-galactosidase (beta Gal) whose expression was driven by the promoter of either the cytomegalovirus early gene, the keratin 12 gene or the keratocan gene, were characterized by critical micelle concentration (CMC), dynamic light scattering (DLS), and atomic force microscopy (AFM). Transgene expression in ocular tissue after gene delivery was analyzed by 5-bromo-4-chloro-3-indolyl-beta-D-galactoside (X-Gal) color staining, 1,2-dioxetane beta-Gal enzymatic activity measurement, and real-time polymerase chain reaction (PCR) analysis. The delivery mechanisms of plasmid-PM on mouse and rabbit corneas were evaluated by EDTA and RGD (arginine-glycine aspartic acid) peptide. RESULTS: The sizes of the three plasmid-PM complexes were around 150-200 nm with unimodal distribution. Enhanced stability was found for three plasmid-PM formulations after DNase I treatment. After six doses of eye drop delivery of pK12-Lac Z-PM three times a day, beta-Gal activity was significantly increased in both mouse and rabbit corneas. Stroma-specific Lac Z expression was only found in pKera3.2-Lac Z-PM-treated animals with pretreatment by 5 mM EDTA, an opener of junctions. Lac Z gene expression in both pK12-Lac Z-PM and pKera3.2-Lac Z-PM delivery groups was decreased by RGD peptide pretreatment. CONCLUSIONS: Cornea epithelium- and stroma-specific gene expression could be achieved using cornea-specific promoters of keratin 12 and keratocan genes, and the gene was delivered with PM formulation through non-invasive, eye drop in mice and rabbits. The transfection mechanism of plasmid-PM may involve endocytosis and particle size dependent paracellular transport. PMID- 17724779 TI - Functional genomics of commercial baker's yeasts that have different abilities for sugar utilization and high-sucrose tolerance under different sugar conditions. AB - In the modern baking industry, high-sucrose-tolerant (HS) and maltose-utilizing (LS) yeast were developed using breeding techniques and are now used commercially. Sugar utilization and high-sucrose tolerance differ significantly between HS and LS yeasts. We analysed the gene expression profiles of HS and LS yeasts under different sucrose conditions in order to determine their basic physiology. Two-way hierarchical clustering was performed to obtain the overall patterns of gene expression. The clustering clearly showed that the gene expression patterns of LS yeast differed from those of HS yeast. Quality threshold clustering was used to identify the gene clusters containing upregulated genes (cluster 1) and downregulated genes (cluster 2) under high sucrose conditions. Clusters 1 and 2 contained numerous genes involved in carbon and nitrogen metabolism, respectively. The expression level of the genes involved in the metabolism of glycerol and trehalose, which are known to be osmoprotectants, in LS yeast was higher than that in HS yeast under sucrose concentrations of 5-40%. No clear correlation was found between the expression level of the genes involved in the biosynthesis of the osmoprotectants and the intracellular contents of the osmoprotectants. The present gene expression data were compared with data previously reported in a comprehensive analysis of a gene deletion strain collection. Welch's t-test for this comparison showed that the relative growth rates of the deletion strains whose deletion occurred in genes belonging to cluster 1 were significantly higher than the average growth rates of all deletion strains. PMID- 17724780 TI - The pursuit of palau'amine. AB - Since its discovery in 1993, the marine natural product palau'amine has intrigued natural product chemists. Its exotic molecular architecture and purported bioactivity made it an ideal target for synthesis. However, as the years went by and related marine alkaloids were isolated, a skeptical eye was cast on the structure of palau'amine; recently these suspicions were confirmed and the structure of palau'amine revised. This Minireview gives a careful overview of the structural revision and its ramifications to both its biogenesis and total synthesis. PMID- 17724781 TI - Cooking activities during the Middle Ages: organic residues in ceramic vessels from the Sant'Antimo Church (Piombino-Central Italy). AB - A combined gas chromatography-electron ionization (GC-EI), atmospheric pressure chemical ionization (APCI) mass spectrometry (MS) and MS/MS approach has been used for characterizing organic residues of ceramic vessels of different forms and dimensions recovered from a vault of the apse of the 13th century church of Sant'Antimo in Piombino (Central Italy). The artifacts studied in this investigation are pots, jugs, colanders and pans probably used for cooking meals or as food containers. GC-MS has shown the presence of different fatty acids and other nonpolar markers, while APCI ionization proved to be particularly useful in the detection of diterpenoids and diacylglycerols. The data show that some organic markers may be of animal origin, while others are typical constituents or biodegradation products of vegetables. This allows one to propose the main use of these articles as vessels for cooking meat and maybe vegetable broths and soups. As there is no strict correlation between organic markers and shape, form and dimension of the ceramic vessel, it appears that the different objects probably served the same function. Chemical characterization of the organic residues of ceramic vessels, together with all the other archaeological data, contributes to a better understanding of their uses and the customs of people in the Middle Ages in Central Italy. PMID- 17724782 TI - Sensitivity analysis of intention-to-treat estimates when withdrawals are related to unobserved compliance status. AB - In the presence of dropout, intent(ion)-to-treat analysis is usually carried out using methods that assume a missing-at-random (MAR) dropout mechanism. We investigate the potential bias caused by assuming MAR when the dropout is related to unobserved compliance status. A framework to assess the magnitude of bias in the context of pre- and post-test design (PPD) with two treatment arms is presented. Scenarios with all-or-none and partial compliance level are investigated. Using two simulated data sets and actual data from an e-mental health trial, we demonstrate the utility of sensitivity analyses to assess the bias magnitude and show that they are plausible options when some knowledge of compliance behaviour in the dropout exists. We recommend that our approach be used in conjunction with methods of analysis which assume MAR in estimating the ITT effect. PMID- 17724783 TI - Investigating the presence of pesticide transformation products in water by using liquid chromatography-mass spectrometry with different mass analyzers. AB - Many pesticide transformation products (TPs) can reach environmental waters as a consequence of their normally having a higher polarity than their parent pesticides. This makes the development of analytical methodology for reliable identification and subsequent quantification at the sub-microgram per liter levels necessary, as required under current legislation. In this paper we report the photodegradation of several pesticides frequently detected in environmental waters from the Spanish Mediterranean region using the high-resolution and exact mass capabilities of hybrid quadrupole time-of-flight mass spectrometry (QTOF MS) hyphenated to liquid chromatography (LC). Once the main photodegradation/hydrolysis products formed in aqueous media were identified, analytical methodology for their simultaneous quantification and reliable identification in real water samples was developed using on-line solid-phase extraction (SPE)-LC-tandem MS with a triple-quadrupole (QqQ) analyzer. The methodology was validated in both ground and surface water samples spiked at the limit of quantification (LOQ) and 10 x LOQ levels, i.e. 50 and 500 ng/l, obtaining satisfactory recoveries and precision for all compounds. Subsequent analysis of ground and surface water samples resulted in the detection of a number of TPs higher than parent pesticides. Additionally, several soil interstitial water samples collected from the unsaturated zone were analyzed to explore the degradation/transformation of some pesticides in the field using experimental plots equipped with lisimeters. Several TPs were found in these samples, with most of them having also been detected in ground and surface water from the same area. This paper illustrates the extraordinary potential of LC MS(/MS) with QTOF and QqQ analyzers for qualitative/structural and quantitative analysis, respectively, offering analytical chemists one of the most powerful tools available at present to investigate the presence of pesticide TPs in water. PMID- 17724785 TI - An exploration of the NHS end of life care programme and its potential use for patients with end-stage systemic sclerosis. AB - Systemic sclerosis is an autoimmune connective tissue disorder with the highest case-specific mortality of the rheumatic disorders (Denton and Black, 1999). Despite recent developments in the treatment of systemic sclerosis, patients are still dying from its complications. Therefore the palliative care needs of patients with end-stage systemic sclerosis must be considered. There is little research into palliative care for patients with systemic sclerosis, but clinical experience suggests the level of care has been dependent upon local resources and the experience of the team responsible for the patient's care. The need for equitable, high-quality palliative care for patients with end-stage systemic sclerosis may be met by current developments in end of life care within the UK. The present paper outlines the NHS end of life care programme (DoH, 2003; NICE, 2003) and uses a case study approach to illustrate its application to palliative care in end-stage systemic sclerosis. PMID- 17724784 TI - Estimating complete prevalence of cancers diagnosed in childhood. AB - A method of estimating the complete prevalence of cancers diagnosed in childhood called CHILDPREV (CHILDhood PREValence), is presented. It is a semi-parametric method based on cancer registry data and on the completeness index method. It allows estimating prevalence even when no observation is available (typically older patients alive at the prevalence date may have been diagnosed with cancer before the introduction of the registry). The method was validated on Connecticut Tumor Registry data, which has 62 years of follow-up and provides complete prevalence, and compared with the fully parametric PIAMOD method. Results of complete childhood prevalence estimates based on SEER-9 cancer registries data for acute lymphocytic leukemia and all cancer sites combined are presented. PMID- 17724786 TI - Assessment of clinical nurse specialists in rheumatology using an OSCE. AB - OBJECTIVE: To introduce a new method of assessment; an observed structured clinical examination (OSCE) into a postgraduate course for rheumatology clinical nurse specialists. METHOD: The OSCE was introduced into a physical assessment module, which focused on the nurses' ability to perform an examination of patients' shoulders, knees and hands. A modified blueprinting exercise was used to ensure adequate sampling of the different components of the syllabus. This resulted in five active stations and one rest station. The active stations included history-taking, physical examination of the shoulder, knee and hand complexes and multidisciplinary management plans. To enhance authenticity real, rather than simulated, patients were used where practical. RESULTS: All 11 students passed all stations, the lowest score related to history-taking and the highest score related to devising a management plan. All 11 students rated the OSCE a worthwhile experience reflecting the learning outcomes of the module and recommended that the OSCE should be used to assess the next cohort of students. Eight students found the OSCE too 'anxiety-provoking' and did not want this method of assessment to be used in other modules. All examiners felt this mode of assessment was more valid than the previous assessment format of a viva on a single patient. CONCLUSION: This was the first time an OSCE was used in a postgraduate course to assess the physical examination skills of rheumatology nurse specialists. The course faculty, examiners and students found it was a reliable and valid means of assessment. PMID- 17724787 TI - Rheology of a polymer-based hybrid suspension composed of concentrated poly[(D,L lactide)-co-glycolide] solution and inorganic salt particles. AB - Suspensions composed of a solution of a biodegradable polyester in a volatile organic solvent, and solid inorganic particles of size in the order of hundreds of microns have been very important in the fabrication of porous scaffolds in the field of tissue engineering. This article reports the basic rheological investigations of this complex fluid type. A Couette geometry covered by silicon oil was found to be an appropriate geometry to retain stability of the rheological measurements. Suspension viscosity increased with the particle volume fraction, and the extent of the increase was much larger than that predicted by the Einstein suspension equation. Both start-up dynamics at the inception of steady shear and relaxation after an abrupt change of oscillatory shear frequency in the suspension showed significantly different behaviors from those in the associated polymer solution. Particle reorganization upon change of rheological state was anticipated. PMID- 17724788 TI - The influence of halide-mediated oxidation on algae-born adhesives. AB - Adhesive materials extracted from the brown algae Fucus Serratus were studied. These adhesives are composed of cross-linked alginate and polyphenols oxidized in the presence of KI or KBr. All formulations were capable of adhering to a variety of surfaces, however the adhesion properties were influenced by the halide used. SAXS and TEM experiments revealed that oxidized polyphenols self-assemble into chain-like objects, irrespective of the oxidation conditions. Yet, slight differences in the aggregate size were detected. QCM-D results showed that the kinetics of the oxidation was faster with iodide than with bromide. Moreover, oxidation with iodide generates stiffer networks, suggesting that the interaction between the alginate and the polyphenol could be the cause of the reduced adhesion. PMID- 17724789 TI - Preparation, characterization, and controlled release of novel nanoparticles based on MMA/beta-CD copolymers. AB - A series of random copolymers with different beta-cyclodextrin contents were synthesized by radical copolymerization of MMA with a monovinyl beta-CD monomer. The copolymers were characterized with IR spectroscopy, elemental analysis, DSC, and TGA. Based on these copolymers, their nanoparticles were prepared by using DMF, water, and acetone as solvents. Aqueous dispersions of the nanoparticles were further obtained by dialysis against water. Zetasizer Nano-ZS dynamic light scattering and transmission electron microscopy were employed to characterize the nanoparticles. Using camptothecin as a model drug molecule, the encapsulation efficiency and release behavior of the nanoparticles were investigated. PMID- 17724791 TI - The systemic effects of juvenoids on the red firebug Pyrrhocoris apterus and on the pea aphid Acyrthosiphon pisum with data on life table response. AB - BACKGROUND: A series of juvenoid alcohols and their glycosidic derivatives (juvenogens), synthesized at the Institute of Organic Chemistry and Biochemistry in Prague, commercially used juvenoids and the natural derivatives of juvabione were evaluated for their systemic juvenilizing effect on the red firebug, Pyrrhocoris apterus L., and on the pea aphid, Acyrthosiphon pisum Harris. A life table response experiment was designed, and demographic characteristics were computed for a cohort of A. pisum following chronic exposure to a range of concentrations of the selected trans-isomer of carbamate juvenoid 8 applied via the broad bean (Vicia faba L.) root system. RESULTS: Using the ratio of topical and per os activities, promising effects were found in two alkyl beta-D glucopyranosides (3 and 9) and the trans-isomer of carbamate juvenoid 8 in tests on P. apterus. In A. pisum, the highest systemic activity was found in tests with the trans-isomer of carbamate juvenoid 8. The longevity, the number of offspring per female and the number of offspring per reproducing female significantly decreased with concentrations of 0.05 mg mL(-1) and higher. While the net reproductive rate R(0) and the intrinsic rate of natural increase r(m) displayed similar trends, the generation time G varied slightly between 11.6 and 12.8 days. CONCLUSION: Expected systemic activity of glycosidic juvenogens in P. apterus was not confirmed by exposure of the pea aphid on broad bean treated with aqueous solutions of the compounds. Nevertheless, the carbamate juvenoid alcohol 8 displayed a considerable juvenilizing effect on A. pisum in screening tests. Furthermore, this compound indicated a sublethal effect as the realized fecundity U(x) decreased disproportionately to the age-specific survival L(x) with increased concentration. The population parameters are compared with the data in similar demographic studies and are discussed together with the possibilities of using the compounds of this structural type in practice. PMID- 17724792 TI - Transcriptional silencing of hedgehog-interacting protein by CpG hypermethylation and chromatic structure in human gastrointestinal cancer. AB - Hedgehog-interacting protein (HHIP) was identified as a putative antagonist of the Hh pathway and as a target of Hh signalling. Our aim was to clarify the expression profiles and epigenetic alterations of the HHIP gene in gastrointestinal cancer. The expression and promoter epigenetic status of HHIP in cancer cell lines and freshly resected gastrointestinal cancer tissues were examined using RT-PCR, tissue microarray analysis, methylation-specific PCR, and chromatin immunoprecipitation assay. Cells were treated with the demethylating agent 5-aza-2'-deoxycytidine and/or histone deacetylase inhibitor trichostatin A. WST-8 assays and in vitro invasion assays after treatment with HHIP-specific siRNA were performed. HHIP expression levels were reduced in most of the gastrointestinal cancer cell lines and in a certain subset of cancer tissues, and these were correlated with promoter hypermethylation. A heterochromatic structure characterized by neither acetylated H3 nor acetylated H4, and histone H3 lysine 9 hypermethylation and histone H3 lysine 4 hypomethylation was observed in cancer cells in which the HHIP gene was aberrantly silenced. On the other hand, overexpression of the HHIP gene was also found in some cancer tissues and there were significant correlations between protein expression levels of HHIP and those of Sonic hedgehog (Shh), Indian hedgehog, Patched, and glioma-associated oncogene homologue-1. An association was found between lymph node metastasis and HHIP silencing in colorectal cancer tissues with strong Shh expression and between advanced TNM stage and HHIP silencing in diffuse-type gastric cancer tissues with strong Shh expression. Down-regulation of HHIP expression by siRNA resulted in a significant increase in colon cancer cell growth and invasion in vitro. Silencing of the HHIP gene due to hypermethylation and chromatin remodelling appears to be frequently involved in gastrointestinal tumourigenesis. PMID- 17724793 TI - Impairment of the ubiquitin-proteasome system associated with extracellular transthyretin aggregates in familial amyloidotic polyneuropathy. AB - The ubiquitin-proteasome system (UPS) has been associated with neurodegenerative disorders of intracellular protein aggregation. We have studied the UPS in familial amyloidotic polyneuropathy (FAP), a neurodegenerative disorder caused by extracellular deposition of mutant transthyretin (TTR). The studies were conducted in TTR-synthesizing and non-synthesizing tissues from affected individuals, in transgenic mouse models for FAP, and in neuronal or Schwannoma cell lines cultured with TTR aggregates. In human FAP tissues presenting extracellular TTR aggregates, ubiquitin-protein conjugates were up-regulated, the proteasome levels were decreased and parkin and alpha-synuclein expression were both decreased. A similar response was detected in mouse models for TTR V30M or L55P. On the other hand, the liver, which normally synthesizes variant TTR V30M, did not show this response. Furthermore, transgenic mice immunized to decrease TTR deposition showed a significant reduction in ubiquitin levels and an increase in parkin and alpha-synuclein levels in comparison to control mice. Studies performed in cell lines with aggregates in the medium resulted in increased ubiquitin and decreased parkin levels. The overall results are indicative of TTR deposition as an external stimulus to an intracellular UPS response in FAP. PMID- 17724794 TI - Identification of Lynch syndrome: how should we proceed in the 21st century? AB - Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is the most common form of hereditary colorectal cancer. Although great advances in the understanding of its molecular basis have taken place in the last decade, optimal selection of individuals for HNPCC genetic testing remains controversial. This is especially relevant since colonoscopy has been proven effective for reducing colorectal cancer incidence and mortality in individuals at-risk for this disorder. In this manuscript, we summarize the most significant contributions to this important issue that have appeared in the last few years. PMID- 17724795 TI - Is there a changing trend in surgical management of gastroesophageal reflux disease in children? AB - Gastroesophageal reflux disease (GORD) is a pathological process in infants manifesting as poor weight gain, signs of esophagitis, persistent respiratory symptoms and changes in neurobehaviour. It is currently estimated that approximately one in every 350 children will experience severe symptomatic gastroesophageal reflux necessitating surgical treatment. Surgery for GORD is currently one of the common major operations performed in infants and children. Most of the studies found favour laparoscopic approach which has surpassed open antireflux surgery as the gold standard of surgical management for GORD. However, it must be interpreted with caution due to the limitation of the studies, especially the small number of subject included in these studies. This review reports the changing trends in the surgical treatment of GORD in children. PMID- 17724796 TI - Genetic alterations in pancreatic cancer. AB - The diagnosis of pancreatic cancer is devastating for patients and their relatives as the incidence rate is approximately the same as mortality rate. Only a small percentage, which ranges from 0.4% to 4% of patients who have been given this diagnosis, will be alive at five years. At the time of diagnosis, 80% of pancreatic cancer patients have unresectable or metastatic disease. Moreover, the therapeutic alternatives offered by chemotherapy or radiotherapy are few, if not zero. For all these reasons, there is an imperative need of analyzing and understanding the primitive lesions that lead to invasive pancreatic adenocarcinoma. Molecular pathology of these lesions is the key of our understanding of the mechanisms underlying the development of this cancer and will probably help us in earlier diagnosis and better therapeutic results. This review focuses on medical research on pancreatic cancer models and the underlying genetic alterations. PMID- 17724797 TI - New therapeutic opportunities for hepatitis C based on small RNA. AB - Hepatitis C virus (HCV) infection is one of the major causes of chronic liver disease, including cirrhosis and liver cancer and is therefore, the most common indication for liver transplantation. Conventional antiviral drugs such as pegylated interferon-alpha, taken in combination with ribavirin, represent a milestone in the therapy of this disease. However, due to different viral and host factors, clinical success can be achieved only in approximately half of patients, making urgent the requirement of exploiting alternative approaches for HCV therapy. Fortunately, recent advances in the understanding of HCV viral replication and host cell interactions have opened new possibilities for therapeutic intervention. The most recent technologies, such as small interference RNA mediated gene-silencing, anti-sense oligonucleotides (ASO), or viral vector based gene delivery systems, have paved the way to develop novel therapeutic modalities for HCV. In this review, we outline the application of these technologies in the context of HCV therapy. In particular, we will focus on the newly defined role of cellular microRNA (miR-122) in viral replication and discuss its potential for HCV molecular therapy. PMID- 17724798 TI - Importance of MutL homologue MLH1 and MutS homologue MSH2 expression in Turkish patients with sporadic colorectal cancer. AB - AIM: To assess the incidence of MLH1 (the human MutL homologue) and MSH2 (the human MutS homologue) protein expression in Turkish patients with sporadic colorectal cancers and to compare their survival and clinicopathological features. METHODS: We validated the tissue microarray technology in 77 colorectal carcinomas by analyzing the immunohistochemical expression of proteins involved in two main pathways of colorectal carcinogenesis: p53 protein for loss of heterozygosity tumors; MLH1 and MSH2 proteins for microsatellite instability (MSI). RESULTS: Our analysis showed that 29 (39.2%) had loss of MLH1 expression, 5 (6.8%) had loss of MSH2 expression and 2 cases had loss of expression of both proteins. We found that 60% of MSH2-negative tumors were located in the right side of the colon; all MSH2-negative cases were women. In addition, the loss of MSH2 expression was correlated with low p53 expression. Neither MLH1 nor MSH2 expressions were associated with prognosis, although there seemed a tendency of longer survival (71.7 +/- 8.65 mo vs 47.08 +/- 5.26 mo) for the patients with MLH1-negative versus MLH1-positive carcinomas. There were not significant differences in overall and recurrence-free survival among MLH1/MSH2-positive and negative cases. CONCLUSION: Our data supports that Turkish patients with MLH1- and MSH2-defective tumors have some distinct features from each other. Although prognostic importance remains controversial, immunohistochemical analysis of mismatch repair genes may be used as a routine histopathological examination of sporadic colorectal carcinomas. PMID- 17724799 TI - H pylori seropositivity and cytokine gene polymorphisms. AB - AIM: To investigate whether the pro- and anti-inflammatory cytokine gene polymorphisms, IL1B-511C/T, IL1B-31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G, interact with smoking and drinking habits to influence infection with H pylori. METHODS: The subjects were 410 Japanese transit company employees. C-reactive protein and conventional cardiovascular risk factors were evaluated. Serum anti-H pylori antibodies were measured. The genotypes of IL1B-511C/T, IL1B 31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G polymorphisms were determined by allelic discrimination using fluorogenic probes and a 5' nuclease assay. RESULTS: In gender- and age-adjusted logistic analyses, the subjects with TNF-857T/T had a significantly lower odds ratio (OR) for H pylori seropositivity (reference -857C/C; OR = 0.15, 95% CI: 0.03-0.59, P = 0.007). After stratification according to smoking and drinking status, among never-smokers, the subjects with IL1B-511C/T had a significantly lower OR (reference -511C/C; OR = 0.30, 95% CI: 0.10-0.90, P = 0.032). Among drinkers in the 1-5 times/wk category, the subjects with IL1B-511T/T had a significantly lower OR (reference C/C; OR = 0.38, 95% CI: 0.16-0.95, P = 0.039), and the subjects with IL1B-31C/T and T/T had a significantly higher OR (reference C/C; C/T: OR = 2.59, 95% CI, P = 0.042: 1.04 6.47; C/C: OR = 3.17, 95% CI: 1.23-8.14, P = 0.017). Among current smokers, the subjects with IL6-634C/G had a significantly higher OR (reference C/C; OR = 2.28, 95% CI: 1.13-4.58, P = 0.021). However, the interactions terms between the aforementioned genotypes and lifestyles were not statistically significant. CONCLUSION: Contrary to previous findings, the results herein suggest that the TNF-857T/T genotype may be protective against chronic infection with H pylori. Drinking and smoking habits may influence the effect of cytokine gene polymorphisms. Further studies are required to clarify the effects of the pro- and anti-inflammatory cytokine polymorphisms and gene-environmental interactions on H pylori infection. PMID- 17724800 TI - Therapeutic proteasome inhibition in experimental acute pancreatitis. AB - AIM: To establish the therapeutic potential of proteasome inhibition, we examined the therapeutic effects of MG132 (Z-Leu-Leu-Leu-aldehyde) in an experimental model of acute pancreatitis. METHODS: Pancreatitis was induced in rats by two hourly intraperitoneal (ip) injections of cholecystokinin octapeptide (CCK; 2 x 100 microg/kg) and the proteasome inhibitor MG132 (10 mg/kg ip) was administered 30 min after the second CCK injection. Animals were sacrificed 4 h after the first injection of CCK. RESULTS: Administering the proteasome inhibitor MG132 (at a dose of 10 mg/kg, ip) 90 min after the onset of pancreatic inflammation induced the expression of cell-protective 72 kDa heat shock protein (HSP72) and decreased DNA-binding of nuclear factor-kappaB (NF-kappaB). Furthermore MG132 treatment resulted in milder inflammatory response and cellular damage, as revealed by improved laboratory and histological parameters of pancreatitis and associated oxidative stress. CONCLUSION: Our findings suggest that proteasome inhibition might be beneficial not only for the prevention, but also for the therapy of acute pancreatitis. PMID- 17724802 TI - Comparison of four proton pump inhibitors for the short-term treatment of esophagitis in elderly patients. AB - AIM: To compare efficacy and tolerability of four proton pump inhibitors (PPIs) commonly used in the short-term therapy of esophagitis in elderly patients. METHODS: A total of 320 patients over 65 years with endoscopically diagnosed esophagitis were randomly assigned to one of the following treatments for 8 wk: (1) omeprazole 20 mg/d; (2) lansoprazole 30 mg/d; (3) pantoprazole 40 mg/d, or (4) rabeprazole 20 mg/d. Major symptoms, compliance, and adverse events were recorded. After 8 wk, endoscopy and clinical evaluation were repeated. RESULTS: Per protocol and intention to treat healing rates of esophagitis were: omeprazole = 81.0% and 75.0%, lansoprazole = 90.7% (P = 0.143 vs omeprazole) and 85.0%, pantoprazole = 93.5% (P = 0.04 vs omeprazole) and 90.0% (P = 0.02 vs omeprazole), rabeprazole = 94.6% (P = 0.02 vs omeprazole) and 88.8% (P = 0.04 vs omeprazole). Dividing patients according to the grades of esophagitis, omeprazole was significantly less effective than the three other PPIs in healing grade 1 esophagitis (healing rates: 81.8% vs 100%, 100% and 100%, respectively, P = 0.012). Pantoprazole and rabeprazole (100%) were more effective vs omeprazole (89.6%, P = 0.0001) and lansoprazole (82.4%, P = 0.0001) in decreasing heartburn. Pantoprazole and rabeprazole (92.2% and 90.1%, respectively) were also more effective vs lansoprazole (75.0%, P < 0.05) in decreasing acid regurgitation. Finally, pantoprazole and rabeprazole (95.2% and 100%) were also more effective vs lansoprazole (82.6%, P < 0.05) in decreasing epigastric pain. CONCLUSION: In elderly patients, pantoprazole and rabeprazole were significantly more effective than omeprazole in healing esophagitis and than omeprazole or lansoprazole in improving symptoms. H pylori infection did not influence the healing rates of esophagitis after a short-term treatment with PPI. PMID- 17724801 TI - Histone deacetylase inhibitor MS-275 alone or combined with bortezomib or sorafenib exhibits strong antiproliferative action in human cholangiocarcinoma cells. AB - AIM: To investigate the antiproliferative effect of the histone deacetylase (HDAC) inhibitor MS-275 on cholangiocarcinoma cells alone and in combination with conventional cytostatic drugs (gemcitabine or doxorubicin) or the novel anticancer agents sorafenib or bortezomib. METHODS: Two human bile duct adenocarcinoma cell lines (EGI-1 and TFK-1) were studied. Crystal violet staining was used for detection of cell number changes. Cytotoxicity was determined by measuring the release of the cytoplasmic enzyme lactate dehydrogenase (LDH). Apoptosis was determined by measuring the enzyme activity of caspase-3. Cell cycle status reflected by the DNA content was detected by flow cytometry. RESULTS: MS-275 treatment potently inhibited the proliferation of EGI-1 and TFK-1 cholangiocarcinoma cells by inducing apoptosis and cell cycle arrest. MS-275 induced apoptosis was characterized by activation of caspase-3, up-regulation of Bax and down-regulation of Bcl-2. Cell cycle was predominantly arrested at the G(1)/S checkpoint, which was associated with induction of the cyclin-dependent kinase inhibitor p21(Waf/CIP1). Furthermore, additive anti-neoplastic effects were observed when MS-275 treatment was combined with gemcitabine or doxorubicin, while combination with the multi-kinase inhibitor sorafenib or the proteasome inhibitor bortezomib resulted in overadditive anti-neoplastic effects. CONCLUSION: The growth of human cholangiocarcinoma cells can be potently inhibited by MS-275 alone or in combination with conventional cytostatic drugs or new, targeted anticancer agents. PMID- 17724804 TI - Perimuscular connective tissue contains more and larger lymphatic vessels than the shallower layers in human gallbladders. AB - AIM: To clarify whether perimuscular connective tissue contains more lymphatic vessels than the shallower layers in human gallbladders. METHODS: Lymphatic vessels were stained immunohistochemically with monoclonal antibody D2-40, which is a specific marker of lymphatic endothelium, in representative sections of 12 normal human gallbladders obtained at the time of resection for colorectal carcinoma liver metastases. In individual gallbladder specimens, nine high-power (x 200) fields with the highest lymphatic vessel density (LVD), termed "hot spots", were identified for each layer (mucosa, muscle layer, and perimuscular connective tissue). In individual hot spots, the LVD and relative lymphatic vessel area (LVA) were measured microscopically using a computer-aided image analysis system. The mean LVD and LVA values for the nine hot spots in each layer were used for statistical analyses. RESULTS: In the mucosa, muscle layer, and perimuscular connective tissue, the LVD was 16.1 +/- 9.2, 35.4 +/- 15.7, and 65.5 +/- 12.2, respectively, and the LVA was 0.4 +/- 0.4, 2.1 +/- 1.1, and 9.4 +/- 2.6, respectively. Thus, both the LVD and LVA differed significantly (P < 0.001 and P < 0.001, respectively; Kruskal-Wallis test) among the individual layers of the wall of the gallbladder, with the highest LVD and LVA values in the perimuscular connective tissue. Most (98 of 108) of the hot spots within the perimuscular connective tissue were located within 500 mum of the lower border of the muscle layer. CONCLUSION: The perimuscular connective tissue contains more and larger lymphatic vessels than the shallower layers in the human gallbladder. This observation partly explains why the incidence of lymph node metastasis is high in T2 (tumor invading the perimuscular connective tissue) or more advanced gallbladder carcinoma. PMID- 17724803 TI - Expression of angiopoietin-1, 2 and 4 and Tie-1 and 2 in gastrointestinal stromal tumor, leiomyoma and schwannoma. AB - AIM: To investigate the role of angiopoietin (Ang) -1, -2 and -4 and its receptors, Tie-1 and -2, in the growth and differentiation of gastrointestinal stromal tumors (GISTs). METHODS: Thirty GISTs, seventeen leiomyomas and six schwannomas were examined by immunohistochemistry in this study. RESULTS: Ang-1, 2 and -4 proteins were expressed in the cytoplasm of tumor cells, and Tie-1 and 2 were expressed both in the cytoplasm and on the membrane of all tumors. Immunohistochemical staining revealed that 66.7% of GISTs (20 of 30), 76.5% of leiomyomas (13 of 17) and 83.3% of schwannomas (5 of 6) were positive for Ang-1. 83.3% of GISTs (25 of 30), 82.4% of leiomyomas (14 of 17) and 100% of schwannomas (6 of 6) were positive for Ang-2. 36.7% of GISTs (11 of 30), 58.8% of leiomyomas (10 of 17) and 83.3% of schwannomas (5 of 6) were positive for Ang-4. 60.0% of GISTs (18 of 30), 82.4% of leiomyomas and 100% of schwannomas (6 of 6) were positive for Tie-1. 10.0% of GISTs (3 of 30), 94.1% of leiomyomas (16 of 17) and 33.3% of schwannomas (2 of 6) were positive for Tie-2. Tie-2 expression was statistically different between GISTs and leiomyomas (P < 0.001). However, there was no correlation between expression of angiopoietin pathway components and clinical risk categories. CONCLUSION: Our results suggest that the angiopoietin pathway plays an important role in the differentiation of GISTs, leiomyomas and schwannomas. PMID- 17724805 TI - Diagnostic accuracy of a rapid fecal test to confirm H pylori eradication after therapy: prospective comparison with a laboratory stool test. AB - AIM: To investigate the clinical performances of rapid stool test (ImmunoCard STAT HpSA, Meridian Diagnostic Inc.) in the evaluation of eradication therapy of H pylori and to compare it with a well-known and validated laboratory stool test (Amplified IDEA Hp StAR, Dako). METHODS: Stool samples of 122 patients were evaluated after eradication therapy of H pylori. H pylori status was assessed by 13C-urea breath test (UBT). Stool specimens were tested using either the rapid immunoassay kit or the laboratory immunoassay kit. RESULTS: Forty-three patients were infected and 79 non-infected. Sensitivity and specificity of ImmunoCard STAT and Hp StAR were 58.14% and 76.4%, and 97.47% and 98.73%, respectively (P > 0.05). Overall agreement between the two tests was 92.6% (113 of 122 cases). CONCLUSION: ImmunoCard STAT seems to have rather low performances, and it cannot be regarded as a reliable tool in the post-treatment setting. Also Hp StAR cannot be recommended to confirm H pylori eradication after treatment. PMID- 17724806 TI - Crohn's disease in one mixed-race population in Brazil. AB - AIM: To evaluate the classification and severity of Crohn's disease in different racial groups. METHODS: Patients with Crohn's disease from the outpatient clinic of the University Hospital Prof. Edgard Santos were enrolled in the study. This hospital is a reference centre for inflammatory bowel disease. Race was determined using self-identification. The Vienna's classification was applied for all subjects. The severity of Crohn's disease was determined according to the number of surgical procedures, hospital admissions in the last year and treatment with steroids and immunosuppressors. Statistical analysis was calculated using t test for means, chi2 or F for proportions. A P value < 0.05 was considered to be significant. RESULTS: Sixty-five patients were enrolled. Non-white patients were more frequently diagnosed with Crohn's disease in the age less than 40 years than white patients. The behaviour of disease was similar in both groups with a high frequency of the penetrating form. There was a tendency for non-white patients to have a greater frequency of hospital admissions in the last year compared to white subjects. Non-whites also had a higher rate of colonic and upper gastrointestinal involvement, and were also more frequently on treatment with immunossupressors than white patients although this difference was not statistically significant. CONCLUSION: Non-white patients with Crohn's disease had an earlier diagnosis and appeared to have had a more severe disease presentation than white patients. PMID- 17724807 TI - Is intra-operative cholangiography necessary during laparoscopic cholecystectomy? A multicentre rural experience from a developing world country. AB - AIM: To evaluate the feasibility and safety of performing laparoscopic cholecystectomy (LC) in non-teaching rural hospitals of a developing country without intra-operative cholangiography (IOC). To evaluate the possibility of reduction of costs and hospital stay for patients undergoing LC. METHODS: A prospective analysis of patients with symptomatic benign diseases of gall bladder undergoing LC in three non-teaching rural hospitals of Kashmir Valley from Jan 2001 to Jan 2007. The cohort represented a sample of patients requiring LC, aged 13 to 78 (mean 47.2) years. Main outcome parameters included mortality, complications, re-operation, conversion to open procedure without resorting to IOC, reduction in costs borne by the hospital, and the duration of hospital stay. RESULTS: Twelve hundred and sixty-seven patients (976 females/291 males) underwent laparoscopic cholecystectomy. Twenty-three cases were converted to open procedures; 12 patients developed port site infection, nobody died because of the procedure. One patient had common bile duct (CBD) injury, 4 patients had biliary leak, and 4 patients had subcutaneous emphysema. One cholecystohepatic duct was detected and managed intraoperatively, 1 patient had retained CBD stones, while 1 patient had retained cystic duct stones. Incidental gallbladder malignancy was detected in 2 cases. No long-term complications were detected up to now. CONCLUSION: LC can be performed safely even in non-teaching rural hospitals of a developing country provided proper equipment is available and the surgeons and other team members are well trained in the procedure. It is stressed that IOC is not essential to prevent biliary tract injuries and missed CBD stones. The costs to the patient and the hospital can be minimized by using reusable instruments, intracorporeal sutures, and condoms instead of titanium clips and endobags. PMID- 17724808 TI - Micrometastasis in surrounding liver and the minimal length of resection margin of primary liver cancer. AB - AIM: To describe the distribution of micrometastases in the surrounding liver of patients with primary liver cancer (PLC), and to describe the minimal length of resection margin (RM) for hepatectomy. METHODS: From November 2001 to March 2003, 120 histologically verified PLC patients without macroscopic tumor thrombi or macrosatellites or extrahepatic metastases underwent curative hepatectomy. Six hundreds and twenty-nine routine pathological sections from these patients were re-examined retrospectively by light microscopy. In the prospective study, curative hepatectomy was performed from November 2001 to March 2003 for 76 histologically verified PLC patients without definite macroscopic tumor thrombi or macrosatellites or extrahepatic metastases in preoperative imaging. Six hundreds and forty-five pathological sections from these patients were examined by light microscopy. The resected liver specimens were minutely examined to measure the resection margin and to detect the number of daughter tumor nodules, dominant lesions, and macroscopic tumor thrombi inside the lumens of the major venous system. The paraffin sections were microscopically examined to detect the microsatellites, microscopic tumor thrombi, fibrosis tumor capsules, as well as capsule invasion and the distance of histological spread of the micrometastases. RESULTS: In the retrospective study, 70 micrometastases were found in surrounding liver in 26 of the 120 cases (21.7%). The farthest distance of histological micrometastasis was 3.5 mm, 5.3 mm and 6.0 mm in 95%, 99% and 100% cases, respectively. Macroscopic tumor thrombi or macrosatellites were observed in 18 of 76 cases, and 149 micrometastases were found in the surrounding live in 25 (43.1%) of 58 cases with no macroscopic tumor thrombi. The farthest distance of histological micrometastasis was 4.5 mm, 5.5 mm and 6.0 mm in 95%, 99% and 100% cases, respectively. Two hundred and sixty-seven micrometastases were found in surrounding liver in 14 (77.8%) out of 18 cases with macroscopic tumor thrombi or macrosatellites. The farthest distance of histological micrometastasis was 18.5 mm, 18.5 mm and 19.0 mm in 95%, 99% and 100% cases, respectively. CONCLUSION: The required minimal length of RM is 5.5 mm and 6 mm respectively to achieve 99% and 100% micrometastasis clearance in surrounding liver of PLC patients without macroscopic tumor thrombi or macrosatellites, and should be greater than 18.5 mm to obtain 99% micrometastasis clearance in surrounding liver of patients with macroscopic tumor thrombi or macrosatellites. PMID- 17724809 TI - Association of the frequency of peripheral natural killer T cells with nonalcoholic fatty liver disease. AB - AIM: To investigate whether changes in the frequency of peripheral natural killer T (NKT) cells were correlated with liver disease in patients who had metabolic predispositions to nonalcoholic fatty liver disease (NAFLD). METHODS: Peripheral blood samples were obtained from 60 Chinese NAFLD patients and 60 age and gender matched healthy controls. The frequency of peripheral NKT cells was detected by flow cytometry. Clinical and laboratory data were collected for further analysis. RESULTS: NAFLD patients had a lower frequency of peripheral NKT cells than healthy controls (1.21% +/- 0.06% vs 1.62% +/- 0.07%, P < 0.001). Further analysis revealed that the frequency of peripheral NKT cells was negatively correlated with body mass index, waist circumference and serum levels of alanine aminotransferase. Logistic regression analysis revealed that elevated body mass index [hazard ratio (HR): 2.991], aspartate aminotransferase levels (HR: 1.148) and fasting blood sugar (HR: 3.133) increased the risk of NAFLD, whereas an elevated frequency of peripheral NKT cells (HR: 0.107) decreased the risk. CONCLUSION: Changes in the frequency of peripheral NKT cells were correlated with NAFLD and a decreased frequency of peripheral NKT cells was a risk factor for NAFLD. PMID- 17724810 TI - Effect of preoperative transcatheter arterial chemoembolization on proliferation of hepatocellular carcinoma cells. AB - AIM: To evaluate the effect of preoperative transcatheter arterial chemoembolization (TACE) on proliferation of hepatocellular carcinoma (HCC) cells. METHODS: A total of 136 patients with HCC underwent liver resection. Of 136 patients, 79 patients received 1 to 5 courses of TACE prior to liver resection (TACE group), who were further subdivided into four groups: Group A (n = 11) who received 1 to 4 courses of chemotherapy alone; Group B (n = 33) who received 1 to 5 courses of chemotherapy combined with iodized oil; Group C (n = 23) who received 1 to 3 courses of chemotherapy combined with iodized oil and gelatin sponge; and Group D (n = 12) who received 1 to 3 courses of chemotherapy combined with iodized oil, ethanol and gelatin sponge. The other 57 patients only received liver resection (non-TACE group). The expressions of Ki-67 and proliferating cell nuclear antigen (PCNA) protein were detected in the liver cancer tissues by immunohistochemical method. RESULTS: The Ki-67 protein expression was significantly lower in Groups C and D as compared with non-TACE group (31.35% +/- 10.85% vs 44.43% +/- 20.70%, 30.93% +/- 18.10% vs 44.43% +/- 20.70%, respectively, P < 0.05). The PCNA protein expression was significantly lower in Groups C and D as compared with non-TACE group (49.61% +/- 15.11% vs 62.92% +/- 17.21%, 41.16% +/- 11.83% vs 62.92% +/- 17.21%, respectively, P < 0.05). The Ki-67 protein expression was significantly higher in Group A as compared with non-TACE group (55.44% +/- 13.72% vs 44.43% +/- 20.70%, P < 0.05). The PCNA protein expression was significantly higher in Groups A and B as compared with non-TACE group (72.22% +/- 8.71% vs 62.92% +/- 17.21%, 69.91% +/- 13.38% vs 62.92% +/- 17.21%, respectively, P < 0.05). CONCLUSION: Preoperative multi-material TACE suppresses the proliferation of HCC cells, while a single material embolization and chemotherapy alone enhance the proliferation of HCC cells. PMID- 17724811 TI - Intestinal Kaposi's sarcoma may mimic gastrointestinal stromal tumor in HIV infection. AB - Diffuse intestinal Kaposi's sarcoma shares macroscopic and histopathologic features with gastrointestinal stromal tumors. Correct diagnosis may pose a clinical challenge. We describe the case of a young HIV-1-infected African lady without advanced immunodeficiency, who presented with a diffuse spindle cell tumor of the gut. Initial diagnosis was of a gastrointestinal stromal tumor, based on endoscopy and histopathology. Further evaluation revealed evidence for human herpesvirus 8 (HHV8) and the diagnosis had to be changed to diffuse intestinal Kaposi's sarcoma. Antiretroviral triple therapy together with chemotherapy was commenced, and has led to the rapid remission of intestinal lesions. With a background of HIV infection, the presence of HHV8 as the causative agent of Kaposi's sarcoma should be determined, as distinct treatment is indicated. PMID- 17724812 TI - Gallbladder endometriosis as a cause of occult bleeding. AB - A 17-year-old girl with colicky abdominal pain and chronic anemia presented to the gastrointestinal service of the University Hospital of Essen. In the routine workup, there were no pathological findings despite the anemia. Because of the fluctuation of symptoms with a climax at the time of menstruation, consecutive ultrasound studies were performed revealing a visible mass inside the gallbladder. This finding was confirmed by a magnetic resonance imaging (MRI) study performed at the same time. Because of the severe anemia by that time, a cholecystectomy was performed, and histology reconfirmed the diagnosis of isolated gallbladder endometriosis. The patient recovered well and has had no recurrence of the disease to date. PMID- 17724813 TI - Radiotherapy for multiple brain metastases from hepatocellular carcinomas. AB - A 78-year-old man with liver cirrhosis was found to have multiple hepatocellular carcinomas (HCCs) and underwent 3 sessions of transcatheter arterial chemoembolization. Fourteen months after diagnosis, the patient presented with left hemiparesis. Contrast-enhanced magnetic resonance imaging showed multiple metastases with ring-shaped enhancement in the cerebrum and cerebellum. There were no metastases to other organs. The metastatic lesions almost completely disappeared after whole-brain radiotherapy with a total dose of 50 Gy. Neurologic symptoms decreased, and the patient's quality of life improved. The patient underwent 2 more sessions of transcatheter arterial chemoembolization. Twelve months after the diagnosis of brain metastasis, the patient remains alive. The present case indicates that radiotherapy can improve quality of life and prolong survival in some patients with brain metastases from HCCs. PMID- 17724814 TI - Hepatocellular carcinoma masquerading as a bleeding gastric ulcer: a case report and a review of the surgical management. AB - Hepatocellular Carcinoma (HCC) is a common malignancy worldwide. While bleeding from the gastrointestinal tract (BGIT) has a well known association with HCC, such cases are mainly due to gastric and esophageal varices. BGIT as a result of invasion of the gastrointestinal tract by HCC is extremely rare and is reportedly associated with very poor prognosis. We describe a 67-year-old male who presented with BGIT. Endoscopy showed the site of bleeding to be from a gastric ulcer, but endoscopic therapy failed to control the bleeding and emergency surgery was required. At surgery, the ulcer was found to have arisen from direct invasion of the gastrointestinal tract by HCC of the left lobe. Control of the bleeding was achieved by surgical resection of the HCC en-bloc with the lesser curve of the stomach. The patient remains alive 33 mo after surgery. Direct invasion of the gastrointestinal tract by HCC giving rise to BGIT is very uncommon. Surgical resection may offer significantly better survival over non-surgical therapy, especially if the patient is a good surgical candidate and has adequate functional liver reserves. Prognosis is not uniformly grave. PMID- 17724815 TI - Intractable bleeding from solitary mandibular metastasis of hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) metastasizes to the mandible is infrequently seen. Solitary bony metastasis to the mandible is rarer. The intractable bleeding caused by rupture of the metastatic HCC is challenging to clinicians. We present a case of a 74-year-old woman with HCC under control without progression for 3 years. Left facial swelling and episodes of bleeding developed recently and biopsy revealed a metastatic HCC. Computer tomography showed a large tumor in parapharyngeal space with evident mandibular ramus destruction. Bleeding occurred from the metastatic tumor but could not be controlled by electrocauterization, Surgical, tissue glue, and bone wax and angiographic embolization. Palliative radiotherapy (2400 cGy in 6 fractions) was tried and the intractable bleeding was successfully stopped after the radiotherapy. Because of the hypervascular and osteolytic nature of the solitary mandibular metastatic lesion, the bleeding was troublesome. Radiotherapy provided successful control of intractable bleeding from the metastatic tumor. PMID- 17724816 TI - Positron emission tomography/computed tomography with (18)F-fluorodeoxyglucose identifies tumor growth or thrombosis in the portal vein with hepatocellular carcinoma. AB - Patients suffering from hepatocellular carcinoma (HCC) with tumor thrombus in the portal vein generally have a poor prognosis. Portal vein tumor thrombus must be distinguished from portal vein blood thrombus, and this identification plays a very important role in management of HCC. Conventional imaging modalities have limitations in discrimination of portal vein tumor thrombus. The application of positron emission tomography (PET) with (18)F-fluorodeoxyglucose ((18)F-FDG) for discrimination between tumor extension and blood thrombus has been reported in few cases of HCC, while portal tumor thrombosis and portal vein clot identified by (18)F-FDG PET/CT in HCC patients has not been reported so far. We present two HCC cases, one with portal vein tumor thrombus and one thrombosis who were identified with (18)F-FDG PET/CT. This report illustrates the complimentary value of combining the morphological and functional imaging in achieving a correct diagnosis in such clinical situations. PMID- 17724818 TI - Tired of fighting "unrealistic" government. PMID- 17724817 TI - Frequently overlooked and rarely listened to: music therapy in gastrointestinal endoscopic procedures. AB - To elucidate the role of music therapy in gastrointestinal endoscopic procedures following the conflicting outcomes reported in two recent studies. The findings of our recent meta-analysis that examined this matter were discussed in the context of later studies. Our meta-analysis illustrated the beneficial effects of music therapy on patient anxiety levels when used as a single measure of relaxation and analgesia. Beneficial effects were also shown on analgesia and sedation requirements and procedure duration times when used as an adjunct to pharmacotherapy. These findings are in agreement with those of both studies excluded from analysis and those that followed it. Music therapy is an effective tool for stress relief and analgesia in patients undergoing gastrointestinal endoscopic procedures. PMID- 17724819 TI - Students under pressure. PMID- 17724820 TI - Self management the key in chronic illness. PMID- 17724821 TI - [Occupational medicine for risky job individuals]. PMID- 17724822 TI - [Myocardial infarction in automobile transport drivers and occupational performance]. AB - The authors revealed significant deterioration in operative response system parameters determining occupational performance of automobile transport drivers after myocardial infarction. Those parameters appeared to depend on age, duration of coronary symptoms, area and depth of myocardial involvement, number of complications, PMID- 17724823 TI - [Changes in prevalence of atherosclerosis risk factors at young age]. AB - The article deals with results of prospective examination of schoolchildren in Kabardino-Balkaria. Findings are high prevalence of atherosclerosis risk factors both among adolescents and young adults, repeatability of arterial hypertension, dyslipidemias, increased body weight and lower physical activity on repeated examinations, significant increase in cigarette smoking and alcohol consumption with age. PMID- 17724824 TI - [Diabetes mellitus in automobile transport drivers--incidence, occupational performance]. AB - The authors present prevalence of diabetes mellitus and atherosclerosis risk factors among automobile transport drivers, relationships of those factors with the work peculiarities. Findings are deteriorated operative response system parameters in automobile transport drivers having diabetes mellitus and arterial hypertension. PMID- 17724825 TI - [Visual acuity in automobile transport drivers under changed light conditions]. AB - Visual acuity in healthy drivers depends directly on illumination of test objects. This acuity increases with better light conditions in 20-30 years of age, whereas in 35-50 year-olds no significant increase is seen. Lower visual acuity is expected with worse light conditions and vice versa - maximal visual acuity with better illumination. PMID- 17724826 TI - [Application of cell technologies for therapy of chronic renal insufficiency (experimental study)]. AB - The experiments on 29 white non-inbred rats with chronic renal failure (CRF) induced by right-side nephrectomy and coagulation of 1/2-2/3 of parenchyma of the left kidney were made to study the trend in renal function after injection (into renal cortex or intravenously) of cultured stem or progenitor cells from human fetuses (total culture of fetal kidney or mesenchymal stem cells of the bone marrow). In control tests with salt solution functional indices reflected persistence of CRF. On day 4 after introduction of the fetal cells into renal parenchyma renal function improved and normalized in 2 weeks. After intravenous injection of fetal cells CRF reduced slowly, especially after injection of medullary mesenchymal cells with normalization in 1 month. 2.5-3.5 months after the injection test parameters in some rats deteriorated but remained close to normal values. Glomerular filtration after injection of stem and progenitor cells recovered better while canalicular sodium reabsorption underwent normalization but was followed by deterioration. PMID- 17724827 TI - [Acid-base imbalance in acute obstructive uropathies]. AB - The aim of this study was to evaluate impairment of acid-base balance (ABB) in acute obstructive uropathies. Evaluation of acid-base balance was performed by pH, partial carbon dioxide pressure, plasma bicarbonate concentration, buffer bases, basis excess, hydrogen ion concentration. An automatic gas analyzer was used, plasma anion gap was calculated. Characteristic ABB alterations in different acute obstructive uropathies were detected. Acidotic shifts in acute obstruction of the upper urinary tracts and its inflammatory complications were assessed pathophysiologically. A comparative study of pathological acid-base disorders in acute supra- and infravesical obstructive uropathies was performed. PMID- 17724828 TI - [Transurethral electrosurgery of a new generation (TURis) in the treatment of the lower urinary tract and prostate diseases]. AB - Surgical interventions were made in 175 patients aged 23-87 years (mean age 64.8 years) with different diseases of the lower urinary tract (adenoma, prostatic cancer, cancer of the urinary bladder, etc.) with application of a new generation of endoscopic technique--transurethral resection in saline (TURis system) with a generator UES-40 SurgMaster (Olympus). Three patients had a cardiac pacemaker. The size of the prostate in prostatic adenoma ranged from 4.8 to 121 cm3 (mean 62.5 cm3), residual urine--92.3 ml (42.6 to 310.2 ml). Duration of surgery averaged 63 min (14 to 127 min). Mean amount of the resected tissue in sclerosis of urinary bladder cervix was 7 g (5-11 g), in prostatic adenoma--41 g (10-85 g), prostatic cancer--27 g (17-49 g). In postoperative period tamponade of the urinary bladder developed in 2 (1.5%) patients. Red cell transfusions were not necessary. Incontinence was observed in 7 (5.3%) patients after removal of urethral catheter, in 5 (3.8%) patients it stopped spontaneously to the time of discharge from the hospital, 2 (1.5%) patients with prostatic cancer retained partial orthostatic incontinence. TURis raised Qmax from 8.1 to 19.8 ml/s, on the average. The scores by IPSS fell from 20.8 to 7.5, QoL--from 5.1 to 3.7, on the average. Residual urine after operation reached 35 ml maximum. Informative value of histological material rose significantly in view of a minimal zone of coagulatory changes in the samples. Standard time limitation for transurethral resection (60-90 min) becomes insignificant in using isotonic irrigation allowing urologists to resect safely larger adenomas than it was possible earlier. PMID- 17724829 TI - [Expediency of switching from combined therapy with prostamol Uno and alpha-1 adrenoblockers to monotherapy with prostamol Uno in patients with prostatic adenoma]. AB - A 9-month randomized open comparative trial was performed of efficacy and safety of combined treatment with prostamol Uno and tamsulosin followed by monotherapy with prostamol Uno. A total of 58 patients with prostatic adenoma (PA) treated with prostamol Uno in combination with tamsulosin were divided into two groups: 28 patients continued the above combined therapy, 30 patients were switched to monotherapy with prostamol Uno. All the patients were examined in the course of 4 visits according to standard protocol requesting information on the disease history, complaints, digital rectal examination, IPSS questionnaire, QOL, uroflowmetry with test for residual urine, transrectal ultrasonography of the prostate, blood test for PSA. The results of the trial show reduction of IPSS and QOL indices in 87% patients. QOL improved both in group 1 after 3 months of combined treatment and in group 2 who continued on monotherapy with prostamol Uno to the end of month 9 (p < 0.05). Q(max) change was statistically the same in both groups. To the end of treatment month 9 the size of the prostate diminished by 6.7 cm3, on the average, in both groups. PSA levels changed insignificantly (p > 0.05). Prostamol Uno was especially safe for hypotensive patients and those on antihypertensive therapy. After discontinuation of tamsulosin 100% patients of group 2 stopped exhibiting symptoms of retrograde ejaculation. None cases of a hypotonic reaction to the drug were registered. Mean cost of a course of therapy in group 1 to that of group 2 was 1:3.16. Thus, pharmacotherapy with prostamol Uno in moderate symptoms of PA is comparable in efficacy with combination prostamol Uno + tamsulosin, is safe and cost-effective. PMID- 17724830 TI - [Efficacy of low-intensity laser radiation and antibacterial therapy in the treatment of chronic prostatitis in the presence of sexually transmitted infections]. AB - We studied 94 patients with chronic prostatitis (CP) in combination with urogenital chlamydiasis. The patients were divided into three groups. Group 1 consisted of 32 patients with bacterial prostatitis and sexually transmitted infection (STI). They were treated with fromilid in a dose 500 mg twice a day. Group 2 (n = 27) received also low-intensity laser radiation (LILR) on the prostatic gland. Group 3 patients (n = 35) with abacterial prostatitis were given fromilid (500 mg twice a day). We studied prostatic hemodynamics with color doppler mapping. A specific feature of prostatic vascularisation in CP and STI versus healthy subjects is heterogeneous decline of vessels density in ischemic zones with parallel decrease in these vessels diameter. A peripheral prostatic zone in CP patients with STI was characterized by lower vascularisation than central one. This deteriorates the course of the disease. The results of the study show that adjuvant LILR in CP patients with STI raises efficacy of therapy by 11%. Investigation of prostate vascularisation and hemodynamics of its vessels in CP patients with STI using transrectal ultrasonography and dopplerography provide detailed information about prostatic structure allowing for lesion zones. This facilitates choice of an optimal complex treatment with application of LELR in peripheral inflammation of the prostate. PMID- 17724831 TI - [Transurethral ureteropyeloscopy with lithotripsy and lithoextraction in children]. AB - High efficacy of endoscopic treatment of urolithiasis in adults stimulated its introduction in the strategy of urolithiasis management in children. 133 ureteropyeloscopies with ureterolithotripsy and ureterolithoextraction was performed in 121 children (boys and girls, age 11 months to 16 years). Concrements (0.5-2.0 cm and larger) located in the caliceal-pelvic segment, ureter, 12 patients had bilateral urolithiasis. Ineffective extracorporeal lithotripsy (ELT) was followed by ureteropyeloscopy in 86 (71%) cases. Rigid and fibroureteropyeloscopes were used. Due to ureterolithotripsy and lithoextraction, concrements were removed completely in 98 (80.9%) patients including 5 children with ligature concrements and 11 children with ureteral strictures which required additional endoureterotomy and removal of ligature. In 23 (18%) cases when migration of concrements and their fragments did not allow complete elimination of the concrements, the kidney in ureteropyeloscopy was drained by catheters or stents with further ELT. Postoperative exacerbation of pyelonephritis treated conservatively was registered in 20 (16.5%) children. Long-term complications were not seen. Thus, transurethral uretheropyeloscopy with lithotripsy and lithoextraction is highly effective, low invasive, safe treatment of urolithiasis in children in failure of ELT. PMID- 17724832 TI - Palifermin: new drug. Prevention of oral mucositis: inappropriate evaluation. AB - (1) Patients treated with high-dose chemotherapy combined with total body irradiation (myeloablative therapy) often develop oral mucositis. Prevention is based mainly on sucking ice during chemotherapy. (2) Palifermin is a growth factor marketed for the prevention of severe oral mucositis in adults with malignant haemopathies who are receiving myeloablative therapy followed by peripheral stem cell autografting. (3) Palifermin has not been compared with sucking ice, despite the efficacy of this simple treatment. (4) In a randomised placebo-controlled double-blind trial involving 212 adult patients treated with high-dose chemotherapy and total body irradiation, palifermin reduced the incidence of severe oral mucositis (63% versus 98%) and its duration (about 3 days versus 9 days). The myeloablative regimen used in this trial is not that commonly used in Europe. The efficacy of palifermin during less aggressive regimens, which cause less severe oral mucositis, is not known. (5) The main adverse events noted in clinical trials were erythema and cutaneous oedema. It is not known whether palifermin increases the long-term risk of cancer. (6) Treatment with palifermin is expensive, 4800.00 euros in France); the optimal dosing schedule is not known and the unit dose chosen by the manufacturer is wastefully large. (7) In practice, it remains to be demonstrated that palifermin is more effective than simply sucking ice. PMID- 17724833 TI - Sunitinib: new drug. For some gastrointestinal stromal tumours. AB - (1) Sunitinib, a tyrosine kinase inhibitor, is marketed for the treatment of advanced-stage and metastatic renal carcinoma, and for second-line treatment of gastrointestinal stromal tumours. Sorafenib arrived on the market almost simultaneously for second-line treatment of kidney cancer. (2) In second-line treatment of kidney cancer, two non comparative trials showed an unusually high rate of at least partial tumour regression with sunitinib (25%, compared to only 2% with sorafenib). Head-to-head trials of the two drugs are lacking. Although indirect comparisons are notoriously unreliable, sunitinib appears to provide longer progression-free survival than sorafenib (about 9 months versus 5.5 months), although overall survival times are similar. (3) Preliminary results of a trial comparing sunitinib with interferon alfa as first-line treatments in 750 patients with kidney cancer show a 6-month event-free survival advantage in the sunitinib arm. The precise overall survival time has not yet been calculated. (4) In 312 patients with gastrointestinal stromal tumours in whom imatinib has failed, a double-blind placebo-controlled trial showed that sunitinib prolonged overall survival time, but potential biases undermine these results. (5) The adverse effect profile of sunitinib appears to be similar to those of imatinib and sorafenib, apart from more thyroid disorders. The principal adverse effects are cutaneous, gastrointestinal, cardiovascular and haematological disorders. Arterial hypertension, sometimes severe, occurred in 16% of patients treated with sunitinib. Other serious adverse events included tumour haemorrhage and pulmonary embolism. A risk of cardiac toxicity leading to heart failure cannot currently be ruled out. (6) Sunitinib is metabolised by cytochrome P450 isoenzyme CYP 3A4, increasing the likelihood of drug interactions. (7) These results support the use of sunitinib as second-line therapy for patients with gastrointestinal stromal tumours. Additional clinical evaluation is needed, however. In first-line treatment of kidney cancer, it is preferable to wait for detailed results of the ongoing trial, especially effects on survival time, before judging the possible advantages and disadvantages of sunitinib compared to interferon alfa. In second line treatment, sorafenib is better-assessed than sunitinib and should therefore be preferred, pending a direct comparison of the two drugs. PMID- 17724834 TI - Sorafenib: new drug. Second-line treatment of kidney cancer: better evaluated than sunitinib. AB - (1) Kidney cancer is infrequent. Most renal malignancies are adenocarcinomas. The prognosis varies markedly from one patient to another. Interferon alfa generally increases survival time by a few months in patients with locally advanced or metastatic cancers, but it has a negative impact on quality of life. (2) Sorafenib inhibits several kinases implicated in angiogenesis and tumour growth. It was recently approved for second-line treatment of advanced-stage kidney cancer. (3) A double-blind placebo-controlled trial involving 903 patients evaluated second-line sorafenib therapy at an oral dose of 400 mg twice a day. Patients with a poor prognosis were not eligible. (4) Sorafenib increased overall survival time by about three months (50% mortality was reached at 19 months in the sorafenib group and at 16 months in the placebo group). The median progression-free survival time also increased by about three months (5.5 months with sorafenib versus about 3 months with placebo). The impact of sorafenib on quality of life was not reported. (5) An indirect comparison shows a higher rate of tumour regression with sunitinib than with sorafenib (25% versus 2%), and also longer progression-free survival (3 to 4 months longer with sunitinib). However, there was no difference between the two drugs in overall survival time, which is the most relevant outcome. Note that no practical conclusions can be drawn from indirect comparisons of this type, as they are subject to too many biases. (6) The main adverse events among patients treated with sorafenib in this trial were cutaneous disorders (about 30% of patients), diarrhoea (about 20%), hypertension (10%), and bleeding (10%). Cases of myocardial ischaemia and neuropathies also occurred. (7) Sorafenib is teratogenic in several animal species. (8) Sorafenib is metabolised by the cytochrome P450 isoenzyme CYP 3A4. The risk of clinically relevant drug interactions is poorly documented. (9) For second-line treatment of patients with kidney cancer and no factors of poor prognosis, available data favour the use of sorafenib, which is better assessed than sunitinib. PMID- 17724835 TI - Pioglitazone + metformin: new drug. A combination product to avoid. AB - More serious adverse effects, and still no tangible proof of efficacy. PMID- 17724836 TI - Pioglitazone + glimepiride: a combination product to avoid. PMID- 17724837 TI - Clopidogrel: new indication. In combination with aspirin: marginal additional benefits. AB - In patients with myocardial infarction who are not eligible for angioplasty, adding clopidogrel to aspirin reduces the overall 15-day mortality rate, but the subsequent outcome is not known. PMID- 17724838 TI - Finasteride: new indication. Benign prostatic hypertrophy: sexual disorders. AB - About 10 fewer cases of acute urinary retention and surgery per 1000 patient years of treatment . . . but about 30 treatment withdrawals due to sexual disorders. PMID- 17724839 TI - Lopinavir + ritonavir tablets: new formulation. More convenient, but minimal evaluation. AB - Kaletra tablets have the advantage of being stored at room temperature, but potential interactions are poorly documented. PMID- 17724840 TI - Nasal azelastine for self-medication: modest symptomatic relief from rhinitis. AB - Azelastine nasal solution is another drug to be marketed for allergic rhinitis, backed by a direct-to-consumer advertising campaign, similar to previous promotional campaigns for oral cetirizine and nasal beclometasone. Self medication with azelastine via the nasal route is acceptable, as it does not seem to provoke serious adverse effects. In contrast, its effectiveness in terms of symptomatic relief from rhinitis is limited. PMID- 17724841 TI - Oral methotrexate: preventing avoidable overdose. AB - (1) Even though the risk has been known since the 1980s, healthcare professionals and patients in many countries still make mistakes involving weekly oral methotrexate therapy. (2) The adverse effects of methotrexate, some of which can be life-threatening, mainly affect haematopoiesis, the kidneys, liver, gastrointestinal tract, skin and mucosa, and lungs. They can occur at low doses, are dose-dependent, and can be precipitated by renal failure or drug interactions. (3) Manifestations of adverse reactions include fever and mouth ulceration. (4) Adverse effects can be due to improper drug administration. (5) Oral methotrexate overdose is linked to errors in prescription, dispensing or administration. It often involves mistakenly taking a weekly dose daily. (6) These errors are preventable. Patients must be informed that methotrexate tablets should be taken weekly: the treatment day should be chosen with the patient when the prescription is written, and this information should be specified on the prescription. It should then be copied onto the box when the drug is dispensed, and also onto an individual treatment register. For additional safety, drug packaging should also contain information that reinforces these measures. PMID- 17724842 TI - Leukaemia due to mitoxantrone. AB - (1) Cases of acute leukaemia (usually myeloblastic) have been attributed to mitoxantrone. (2) A French epidemiological study showed an increased risk of leukaemia in women treated with mitoxantrone for breast cancer, with a relative risk of about 7. The results of studies conducted elsewhere are similar. (3) The time to onset of leukaemia after mitoxantrone exposure ranges from 8 months to several years. The risk is dose-dependent. The excess risk is particularly high when the cumulative dose is above 13 mg/m2. The prognosis for leukaemia due to mitoxantrone is worse than the prognosis for leukaemia with no known cause. (4) Cases of leukaemia have also been reported after the use of mitoxantrone to treat other cancers and multiple sclerosis. (5) This serious adverse effect must be taken into account when choosing a treatment for patients with a relatively long life expectancy. Patients treated with mitoxantrone should be monitored. PMID- 17724843 TI - Angiotensin-II receptor antagonist + diuretic + NSAID = danger! PMID- 17724844 TI - Chronic hepatitis B: a wider range of therapeutic options. AB - (1) An estimated 15% to 25% of patients with chronic hepatitis B die of complications of the disease, such as cirrhosis and liver cancer. (2) In 2000, interferon monotherapy was the first-line treatment for chronic hepatitis B. This article examines the results of trials of peginterferon and nucleoside/nucleotide analogues (adefovir, entecavir, lamivudine), through a systematic review of the literature based on standardised Prescrire methodology. (3) We found no significant new data on interferon alfa administered subcutaneously three times a week: this treatment leads to sustained eradication of HBe antigen (reflecting a lack of viral replication) in 20% to 40% of patients. Adverse effects include a flu-like syndrome, potentially severe psychiatric disorders, and haematological and thyroid problems. (4) A trial comparing peginterferon alfa-2a once a week with interferon alfa-2a three times a week in about 300 patients showed that peginterferon alfa was at least as effective as interferon alfa-2a but that it increased the risk of neutropenia. (5) Three randomised controlled trials show that adding lamivudine to peginterferon does not increase the effect on viral load. Two trials show that peginterferon alfa-2a monotherapy is more effective than lamivudine monotherapy at 48 weeks. (6) In a randomised placebo-controlled trial in more than 600 cirrhotic patients, lamivudine (100 mg/day) reduced the risk of clinical progression in 10% of patients after three years of treatment. (7) The adverse effects of lamivudine are generally mild. Viral resistance occurs frequently and can limit its use. (8) Randomised controlled trials of adefovir dipivoxil show that it is effective after lamivudine failure, and that viral resistance tends to occur later than with lamivudine. When used as first-line treatment, adefovir dipivoxil is virologically effective for at least two years in about 25% of patients. Fewer follow-up data are available for adefovir dipivoxil than for lamivudine. Adefovir dipivoxil is nephrotoxic, meaning that blood creatinine levels must be monitored. (9) Entecavir was more effective than lamivudine on viral load and histological inflammation in three comparative trials lasting 96 weeks. However, entecavir may be carcinogenic. (10) In short, the treatment options for patients with chronic hepatitis B improved significantly between 2000 and 2007. Peginterferon alfa is now the first choice treatment, followed by adefovir dipivoxil or lamivudine as second-line treatment and by entecavir as a last resort. Other antivirals are under development. PMID- 17724845 TI - Obesity: weight loss without drugs: a balanced diet avoiding high-calorie foods, plus exercise. AB - (1) Weight loss in obese patients can reduce some of the complications of obesity. (2) To determine which interventions have the greatest and most durable impact on weight, without a risk of serious adverse effects, we conducted a systematic review of the available evidence, based on standardised Prescrire methodology. (3) Clinical trials of treatments for obesity have not taken into account the social, environmental or psychological factors that contribute to obesity, nor the individual's history of obesity and previous treatments, nor the possible impact of dieting on quality of life. These flaws limit the conclusions drawn from these trials. (4) A meta-analysis of 32 randomised controlled trials involving obese patients showed that moderate and well-balanced calorie restriction is more effective than any other diet, resulting in an average weight loss of about 5 kg after one year. (5) A meta-analysis of 35 randomised controlled trials involving obese patients showed that a combination of dieting and increased exercise is more effective than either measure alone. Increasing physical activity also helps to maintain weight loss. (6) A meta-analysis of 19 randomised controlled trials showed that the addition of active support, such as behavioural therapy, makes dietary weight loss measures more effective in obese patients. Behavioural therapy with spousal participation seems to be most effective, with half of trial participants losing about 7 kg after one year. (7) Interventions that do not involve assistance from healthcare professionals are hardly any more effective than dieting alone. (8) In practice, a variety of non drug measures can help obese patients to lose weight. However, they only lead to modest enduring weight loss, and their limited impact on prevention of complications means they should not be pushed too insistently on patients. When patients want assistance with weight loss, their individual body weight history should be carefully analysed before embarking on a weight loss programme. PMID- 17724846 TI - Juvenile idiopathic arthritis: some progress but still many uncertainties. AB - (1) Juvenile idiopathic arthritis is a chronic inflammatory rheumatic disorder of unknown cause. Spontaneous remission is frequent. Between 10% and 20% of patients have ocular involvement. (2) Nonsteroidal antiinflammatory drugs and physiotherapy are the cornerstones of patient management. Intra-articular steroid injection generally provides several months of relief. The place of immunosuppressants is difficult to ascertain, given their uncertain benefits and established long-term risks in children. There is no curative treatment at present. PMID- 17724847 TI - A thioredoxin of Sinorhizobium meliloti CE52G is required for melanin production and symbiotic nitrogen fixation. AB - A miniTn5-induced mutant of a melanin-producing strain of Sinorhizobium meliloti (CE52G) that does not produce melanin was mapped to a gene identified as a probable thioredoxin gene. It was proved that the thiol-reducing activity of the mutant was affected. Addition to the growth medium of substrates that induce the production of melanin (L-tyrosine, guaiacol, orcinol) increased the thioredoxin like (trxL) mRNA level in the wild-type strain. The mutant strain was affected in the response to paraquat-induced oxidative stress, symbiotic nitrogen fixation, and both laccase and tyrosinase activities. The importance of thioredoxin in melanin production in bacteria, through the regulation of laccase or tyrosinase activities, or both, by the redox state of structural or catalytic SH groups, is discussed. PMID- 17724848 TI - Quiz page. Acute renal failure caused by renal allograft infection with C glabrata. PMID- 17724849 TI - [The 49th annual meeting of the Japanese Society of Child Neurology. Osaka, Japan. July 5-7, 2007. Program and Abstracts]. PMID- 17724851 TI - Mastering reimbursement: selecting an E&M service category. PMID- 17724850 TI - NABP/ASCP joint report: model rules for long-term care pharmacy practice. PMID- 17724852 TI - The William Nelson ECG Quiz. PMID- 17724853 TI - Biological dressings for the management of enteric fistulas in the open abdomen: a preliminary report. AB - HYPOTHESIS: Biological dressings can be effective tools in the management of enteric fistulas, which are the nemesis of exposed viscera. DESIGN: Retrospective review of medical records. SETTING: University-affiliated level I trauma center. PATIENTS: Patients with open abdominal cavities and coexistent intestinal fistulas who were treated between January 1, 1999, and July 1, 2006. INTERVENTIONS: Application of biological dressings to fistula sites within open abdominal cavities during serial fascial closure. Biological dressings included cadaveric skin, human acellular dermal matrix, and fibrin sealant. MAIN OUTCOME MEASURES: Enteric fistula closure and healing of the abdominal wound. RESULTS: During the 6 years under review, there were 69 patients with open abdomens. Of these patients, 7 (10%) developed enteric fistulas and underwent application of biological dressings. In 5 patients, fistulas closed and the abdominal wound healed after application of biological dressings. One additional patient healed after fistula resection. Biological dressing treatment and fistula resection both failed in 1 patient. There was no morbidity or mortality attributable to the intervention. CONCLUSIONS: Intestinal fistulas significantly complicate the management of patients with open abdomens. In this case series, biological dressings were effective in achieving fistula closure. A prospective multi institutional study is required to confirm these preliminary encouraging results. PMID- 17724854 TI - Some insight into the vascular endothelia growth factor/erythropoietin relationship. PMID- 17724856 TI - Facility design showcase. Brookhaven Retreat, Semour, Tennessee. PMID- 17724855 TI - Reply to comments on Manoj H. (letter to the editor, Funct Neurol 2006; 21:229). PMID- 17724857 TI - Spectral sexualities: nineteenth-century spiritualism, moral panics, and the making of U.S. obscenity law. PMID- 17724858 TI - Helen Keller and "the empire of the normal.". PMID- 17724859 TI - "Take health from the list of luxuries": labor and the right to health care, 1915 1949. PMID- 17724860 TI - Glowing dishes: radium, Marie Curie, and Hollywood. PMID- 17724861 TI - Denominational difference in Quaker relief work during the Spanish Civil War: the operation of corporate concern and liberal theologies. PMID- 17724862 TI - [Current problems of clinical toxicology in Poland]. PMID- 17724863 TI - [The importance and value of the toxicological and biochemical results in the management of the poisoned patient]. AB - The most important tasks of modern analytic toxicology can be summarized as follows: identification and quantification of toxicants potentially responsible for the intoxication of an emergency patient; confirmation or exclusion of poisoning diagnoses; grading and prognosis of an intoxication; monitoring of elimination therapies; testing for drugs of abuse; exclusion of the presence of central depressants before organ explanation or discontinuation of life support; checking the compliance of patients with prescribed drug therapy; therapeutic drug monitoring. The interpretation of toxicologic results is one of the most difficult tasks in toxicology. It is not always possible to relate symptoms and blood concentrations of drugs and poisons. In many cases, it is necessary to monitor biochemical parameters in the management of poisoned patient. PMID- 17724864 TI - Hydrocarbon toxicity: an analysis of AAPCC TESS data. AB - INTRODUCTION: Human hydrocarbon exposures have the potential to cause significant morbidity and mortality. To determine which hydrocarbons were associated with the most severe adverse outcomes, human exposure data reported to American poison information centers were analyzed. METHODS: Outcome data for single-substance, hydrocarbon exposures reported to the American Association of Poison Control Centers Toxic Exposure Surveillance System from 1994 through 2003 were analyzed. Only cases with definitive medical outcomes were included. Analyses were stratified by five age groups: <6 years, 6-12 years, 13-19 years, 20-59 years, >59 years. Hazard factors were determined by calculating the sum of the major effects and fatalities for each hydrocarbon category and dividing this by the total number of exposures for that category. To normalize the data, the overall rate of major effects and deaths for each age group was assigned hazard factor value of 1. Hydrocarbon categories with a HF of > or = 1.5 were included in the final analyses. Estimated rates of major effect and fatal outcomes (outcomes/1000 people) were also calculated. RESULTS: 318,939 exposures were analyzed. Exposures to benzene, toluene/xylene, halogenated hydrocarbons, kerosene and lamp oil resulted in the highest hazard factor values. CONCLUSIONS: These data demonstrate that hydrocarbons that are absorbed systemically and those with low viscosities are associated with higher hazard factors. The risks associated with hydrocarbons often implicated in abuse by older children and adolescents are also confirmed. PMID- 17724865 TI - The epidemiology of poisonings in infants <6 months of age. AB - Contrary to popular belief, children that are less than six months of age are the common victims of unintentional poisoning. The purpose of this study was to examine the profile of poisoning exposures of children as they matriculate through their first six months of life by examining actual exposure data from a certified regional poison information center. Data analysis revealed that adult caregivers were responsible for the majority of exposures in children 0-3 months of age as a consequence of medication administration errors. Due to enhanced motor skills, children from 4-6 months of age frequently exposed themselves to potential poisons that were within their grasp. Parents and caregivers need to be educated proactively by health care professionals to prevent unintentional poisoning exposures in children less than six months of age. PMID- 17724866 TI - [Quantitative analysis of heart scintigraphy (99mTc-MIBI GSPECT) with regional myocardial wall motion and thickening assessment for detecting myocardial injury in patients after acute paracetamol poisoning]. AB - The aim of the study was to evaluate the myocardium function in acute paracetamol poisoning using 19mTc-MIBI GSPECT. MATERIAL AND METHODS: Under examination there were 25 acutely paracetamol poisoned patients (age: 24.5 +/- 6 years) treated at the Ward of Toxicology and Environmental Diseases. The control group necessary to perform quantitative analysis of myocardial scintigraphy consisted of 20 people examined in Nuclear Medicine Unit with normal results of 99mTc-MIBI GSPECT examination. RESULTS: The quantitative analysis of the heart scintigraphy (GSPECT) revealed that, the average value of left ventricle ejection fraction (EF) in examined women and men after paracetamol poisoning was lower than in control group, while end diastolic (EDV) and end systolic volumes (ESV) were higher; these differences were not statistically significant. Indicators of regional wall motion of the left ventricle were lower for the most of the heart segments. According to the control group, they were significantly lower for anterior and inferior LV segments. Wall thickening analysis revealed the impaired systolic thickening of majority of heart segments in examined group of patients; the wall thickening was the lowest for infero-lateral and septal segments in women and for inferior, infero-lateral and anterior segments in men. CONCLUSIONS: The quantitative analysis of myocardial perfusion scintigraphy (99mTc-MIBI GSPECT) with wall motion and wall thickening assessment, showed that the left ventricle function was usually diffusely depressed in paracetamol poisoned patients. The disturbances of regional wall motion of anterior and inferior wall (LV) were mainly visible. PMID- 17724867 TI - [Evaluation of regional cerebral blood flow using 99mTc-ECD SPECT in ethanol dependent patients: pilot study]. AB - The depressant actions of ethanol in the brain is known. SPECT is non invasive method to measure the regional cerebral blood flow (rCBF) and to evaluate indirectly the brain metabolism. The aim of the study is to evaluate morphologic and functional status of CNS using 99mTc-ECD SPECT in chronic alcoholics. MATERIAL AND METHODS: Examined group consisted of 18 male alcoholic patients aged from 28 to 52 years (x = 42.1 +/- 5.4) treated at the Ward of Toxicology and Environmental Diseaes (Detoxification Unit). Only patients without prior head injury, CNS inflammatory changes, epilepsy, migraine, diabetes mellitus or other systemic injury were included. Alcohol dependence was diagnosed according to ICD 10 criteria. The intensity of withdrawal syndrome was measured using CIWA-A scale. The regional cerebral blood flow (rCBF) was measured using 99mTc-ECD SPECT with the double head E.CAM Siemens gamma camera. The reference group, necessary to obtain a normal values for the gamma camera applied, consisted of 31 healthy subjects (33.32 +/- 10.99 y). RESULTS: The mean values of rCBF in all examined region of frontal and temporal lobes, and in basal ganglia bothsided were significantly lower in the group of alcoholic patients than in the control group. No significant difference between rCBF in occipital lobes except the occipital inferior region, and in parietal lobes except the parietal superior region. Symetrical hypoperfusion (rCBF-2SD) in the frontal lobes was stated in 11 (61.1%), in temporal lobes in 4 (22.2%), in parietal and occipital lobes in 3 (16.7%) of the patients examined. In 7 the patients examined rCBF disturbances in basal ganglia were found (bothsided in 4, leftsided in 2, and rightsided in 2 the patients). Focal rCBF changes in the parietal, frontal and temporal lobes localised mostly on the left hemisphere were stated in 27.8% of the alcoholics examined. In concusion, the metabolic disturbances and the brain morphological changes mostly in frontal and temporal lobes due to chronic alcoholism were detected in the pilot study. A further investigation on more numerous group of ethanol dependent patients and monitoring of the changes in alcoholics who maintain a long-term abstinence from alcohol is needed. PMID- 17724868 TI - Association between 5-hydroxytryptamine 1A receptor gene polymorphism and suicidal behavior. AB - Suicidal behavior is highly correlated with many emotional disturbances and some psychiatric disorders. The biogenic amine, serotonin, is one of the most important neurotransmitter in the central nervous system believed to play a huge role in pathogenesis of some kind of mental disorders. Drugs targeting serotonin receptors like serotonin reuptake inhibitors (SSRIs) are useful in the present therapy of anxiety and depression. Recent studies have reported that genetic factors are associated with development of some psychiatric disorders. Serotonin receptor single nucleotide polymorphism (SNP) has emerged as the subject of controversial result in correlation with suicide attempt. Further studies should be performed to confirm the influence of allelic variation of serotonin receptor on elevated risk of auto-aggression behavior. The aim of our study was to examine the frequency and genotype distribution of C(-1019)G polymorphism of regulatory region 5-HT1A receptor in the group of 65 suicide attempters and 63 persons in the control group. Using allele specific amplification PCR (ASA-PCR), we found that allele G was higher in suicidal attempters. The genotype frequency was significantly different between hospitalized patients and control subjects. The most common intoxication causes were antidepressants (56.9%), analgesics (18.5%) and cardiologic drugs (10.8%). Our data support hypothesis which indicate role of the 5-HT1A C(-1019)G SNP polymorphism in elevated risk of suicidal attempt. PMID- 17724869 TI - [Strategic preparedness of selected hospitals to act during massive chemical disasters]. AB - The aim of our study was the evaluation of strategic preparedness of twelve hospitals in Krakow, Warsaw and the Triple City to give aid during massive chemical accidents. The study was carried on 146 persons, including 9 managers, 31 ward heads, 75 assistants, and 31 ward nurses. In statistical analysis the generalized linear model extended by random factors, particularly the Poisson's regression has been used. In any of the investigated hospitals, there were no plans regarding of action in case of chemical accidents. The knowledge about sources of possible contamination as well as environment threats were insufficient. The majority of the medical staff did not know their role as well as the role of their hospitals in case of a chemical accident. There is an urgent need for courses about the procedures which should be used during chemical accidents. The lack of hospital preparedness to act during chemical disasters in the big cities suggests that a similar situation is common in other such medical units all over the country. Further investigations, especially in the hospitals which are placed near the potentially dangerous factories, should be carried on in the near future. PMID- 17724870 TI - [Logistic preparedness of chosen urban agglomeration hospitals to act during massive chemical disasters]. AB - Twelve hospitals--five form Warsaw, three from Krakow, and four from Gdansk and Gdynia were randomized for the study. The logistic preparedness of hospitals during massive chemical accidents has been investigated. There were 146 probands (9 managers, 31 ward heads, 75 assistants and 31 ward nurses) included in the study. In statistical analysis the generalized linear model extended by random factors, particularly the Poisson's regression has been used. No hospital in the three big cities in the country was prepared for any logistic action in case of massive chemical disaster. There were no stationary and mobile decontamination units in the investigated hospitals. There was no individual protective equipment in any of the analyzed hospitals. There were serious deficits in assortment and amount of antidotes which can be used in the treatment of contaminated patients. As much as 97.2% of respondents pointed the poison information centers as a main source of information in case of chemical accidents. PMID- 17724871 TI - [Essential preparedness of physician to act during massive chemical disasters]. AB - The aim of the study was the evaluation of some aspects of doctors knowledge about the treatment in case of massive chemical accidents. The study was conducted in twelve hospitals in Krakow, Warsaw, and the Triple City. There were 106 doctors (31 ward heads and 75 assistants) included in the study. The questions contained some aspects of: external decontamination, the usage of 0.5% of sodium hypochlorite, the knowledge about the use of selected antidotes and the symptoms of chosen toxidromes. In statistical analysis the generalized linear model extended by random factors, particularly the Poisson's regression was used. The results confirm, that the medical staff is not well prepared to take an effective action in case of a chemical contamination. The essential knowledge of the medical staff in all investigated aspects of chemical safety has been found out to be not satisfactory. There is an urgent need for medical staff to undergo theoretical and practical courses about toxicity of major chemicals. The clinical toxicologists should be asked to prepare up-to-date, advanced methods and regulations for life support in case of heavy chemical accidents. PMID- 17724872 TI - [Suicidal poisoning in relation to use of psychoactive substances in adolescents]. AB - The aim of the study is to assess interrelation between a usage of psychoactive substances and suicidal behaviour of adolescents and young adults (14-19 years). A three groups were included to the prospective study: patients hospitalized at the Krakow Department of Clinical Toxicology because of suicidal poisoning (examined group); patients hospitalized at the Department poisoned acciden tally (first control group); and Krakow secondary school children (second control group). Examined group consisted mostly of females--88%; distribution of gender in both the control groups was equal. Most of adolescents examined were inhabitants of Krakow. Near half of the patients treated due to suicidal attempt attended secondary school. A medication drugs dominated as a cause of poisoning in that group, whereas carbon monoxide dominated in the control group of accidentally poisoned patients. Most of the examined (examined suicidal group and both the control groups) declared alcohol initiation, but intensity of alcohol drinking in suicidal group was much more higher compared to the control groups. 44% of the suicidal patients confirmed the use of narcotics; the difference in relation to the control groups was statistically significant. Most of examined had reached for psychoactive substances in age of 14-16 years, but the age of abuse initiation in the suicidal patients was considerably lower compared to both controls. Marijuana was the most popular, but the suicidal patients also experienced with opioids and cocaine as well as with inhalatory substance abuse. In conclusion, obtained results confirmed statistically significant difference between the use of psychoactive substances in adolescent who attempted to commit suicide and adolescents from the control groups. PMID- 17724873 TI - [Alcohol consumption and the risk of insulin resistance--population based study]. AB - The aim of the study was to assess the relationship between alcohol consumption and insulin resistance in the adult Krakow's inhabitants. MATERIALS AND METHODS: 6000 subjects at age 35-75, participants of the Polish Multicenter Study on Diabetes Epidemiology, were randomized and invited to the study. Finally in 2838 participants the standardized questionnaire examination of the life style especially alcohol consumption was performed. In all persons anthropometric and blood pressure examination was performed. Fasting lipids, fasting and after glucose load glucose and insulin were determined. Glucose tolerance was determined in all study participants according WHO 1999 criteria. Insulin resistance was defined as the highest quartile of the distribution of the HOMA-IR index assessed for population with normal glucose tolerance (NGT). RESULTS: In examined group 472 (29.2%) women and 150 (12.2%) men were abstainers. Alcohol consumption below 10 glday declared 68.4% of women and 54.9% of men, between 10 and 30 g/day--2.0% of women and 24.7% of men, above 30 g/day--8.2% of men and 0.4% of women. In men with normal glucose tolerance the lowest HOMA-IR we observed in the group drinking daily above 30 g of alcohol (2.05 +/- 1.3). In men with impaired glucose tolerance the lowest HOMA-IR was observed in the group drinking daily below 10 g of alcohol, the highest in the group of abstainers (2.81 +/- 2.04 vs. 3.23 +/- 1.72; ns). For men drinking between 10 and 30 g of alcohol daily decreased the risk of insulin resistance at 40% (OR = 0.6; 95% CI: 0.37-0.96), drinking above 30 g daily decreased the risk at 49% (OR = 0.51; 95% CI: 0.27-0.96). We didn't observed this relationship in the group of women. CONCLUSION: Our results confirm positive impact of daily alcohol intake above 10 g for the risk of insulin resistance in the group of men. PMID- 17724874 TI - [Evaluation of ventilation disorders in alcohol addicted males]. AB - The aim of the study was to evaluate the ventilatory disturbances in alcohol addicted males. The examined group consisted of 59 alcoholics acutely poisoned with ethanol. 30 healthy individuals, occasionally drinkers, were the control group. The acetaldehyde concentration in relation to results of spirometric examination was analyzed. It's serum concentration in alcoholics was higher then in the coi* trol group. The frequency of central bronchi obstruction in ethanol dependent patients was significantly higher compared with the control. In examined group negative correlation between serum acetaldehyde concentration and spirometric parameters was noted and statistically significant for FEV1 and VC ones. PMID- 17724875 TI - [Patients with alcohol problem in the Emergency Department of Medical University of Gdansk]. AB - Alcohol misuse are severe financial burden for health care system in Poland. AUDIT and CAGE are two questionnaires used for diagnosis of alcohol abuse. We analyzed the incidence of alcohol problem among emergency unit's patients and correlation of this phenomenon with the reason of admittance to the hospital. 30% patients of Clinical Hospital Emergency Unit of Gdansk misuse alcohol. Injuries and acute intoxications were considerably more frequent reason of attendances to emergency unit in population of patients with drinking problem. AUDIT questionnaire is more effective and sensitive diagnostic instrument comparing to CAGE and may be useful for identification for both, addicted and misusing alcohol patients. PMID- 17724876 TI - [Evaluation of pituitary-gonadal axis in alcohol dependent males]. AB - Chronic alcoholism leads to organic damages of nervous system, the liver and the endocrine system. The aim of the study is to evaluate pituitary-gonadal axis in males chronically dependent with alcohol. MATERIAL AND METHODS: The study group consisted of 50 alcohol dependent men aged 27 to 53 years (40.7 +/- 6.6) treated at the Ward of Toxicology and Environmental Diseases (Detoxification Unit). Al cohol dependence was diagnosed according to ICD-10 criteria. The intensity of withdrawal syndrome was measured using CIWA-A scale. In all the patients anthropometrical measurements and abdominal ultrasonography were performed as well as blood pressure was measured. Levels of gonadotropin, total testosteron, PRL were determined, thyroid and adrenal gland function were assessed and oral glucose tolerance test (OGTT) was performed in all patients. Activity of the liver enzymes, urea and creatine concentration were determined. Erectile dysfunction was assessed using IIEF. 5 questionnaire: in those patients who received < or =21 points an incidence of diabetes mellitus, thyroid gland and cardiovascular diseases was assessed using standardized questionnaire. RESULTS: Alcohol dependency longer than 15 years was stated in 25, longer than 10 years in 9, and longer than 5 years in 16 of examined patients. The moderate withdrawal syndrome was diagnosed in 22, severe withdrawal syndrome in 26 and very severe withdrawal syndrome in 2 of the patients. BMI ranged from 15.8 to 33.8 kg/m2 (mediane 24.67; +/- 0.54 kg/m2). In 24 men erectile dysfunction was diagnosed using IIEF5 questionnaire. No significant difference was noted between level of total testosterone and PRL in the group with or without erectile dysfunction (testosterone: 5.07 +/- 2.41 vs. 4.54 +/- 2.74; PRL: 330.2 +/- 214.2 vs. 307.4 +/ 258.2). Gonadropine level in the group of men with erectile dysfunction was significantly higher than that without erectile dysfunction (LH: 7.4 +/- 5.2 vs. 4.38 +/- 2.23, p < 0.01; FSH: 13.3 +/- 29.3 vs. 4.59 +/- 19.92, p < 0.05). CONCLUSION: The results obtained confirm that secondary stimulation of pituitary gonadal axis in alcoholic men depends on liver function and ethanol toxic effect on gonads. PMID- 17724877 TI - [Carbohydrate metabolism in acute poisoning with xenobiotics]. AB - The aim of the study was to evaluate carbohydrate metabolism in patients hospitalised because of acute intoxication with xenobiotics. MATERIAL AND METHODS: An analysis of 3628 patients (1553 females and 2075 males; age: 40.6 +/- 15.9 y) hospitalized at the Ward of Toxicology and Environmental Diseases because of acute poisoning in 2004-2006 was done. The patients with diabetes mellitus diagnosed prior to hospitalisation were excluded from the analysis. The blood ethanol concentration was measured, medication drugs and/or psychoactive substance screening test were performed in all patients on admission. Fasting glucose level on admission and control level on second or third day of hospitalisation were determined. Risk ratio of hyperglycaemia according to toxic agent was assessed using multiple regression model considering age, gender, and the patient education. RESULTS: In 18.2% (398 males and 254 females) of the patients the blood glucose level on admission was > or = 7.8 mmol/l; in u 3.6% (78 males and 50 females) > or = 11.1 mmol/l. In 24 (0.6%) of the patients glycaemia on admission was < or = 3.5 mmol/l. Control fasting glucose level of > or = 7.0 mmol/l was determined in 115 males and 76 female patients. 42% elevation in risk of hyperglycaemia was noted in acute carbon monoxide poisoning (OR = 1.42; 95% PU: 1.11-1.82). In ethanol intoxicated patients 12% drop in risk of hyperglycaemia was noted (OR = 0.88; 95% PU: 0.72-1.07). Benzodiazepine poisoning diminished risk of hyperglycaemia in 36% (OR=0.64; 95%PU: 0.48-0.84). Risk of hyperglycaemia in poisoning by medicines co-ingested with ethanol was always lower compared to poisoning with the single agent. CONCLUSION: A higher risk of hyperglycaemia was related to acute carbon monoxide poisoning whereas lower risk of hyperglycaemia was attributed to benzodiazepines and alcohol. A frequency of hypoglycaemia in the group of poisoned patients was much more lower compared to hyperglycaemia. PMID- 17724878 TI - The influence of carbamazepine plasma level on blood pressure and some ECG parameters in patients with acute intoxication. AB - BACKGROUND: Carbamazepine (CBZ) is an antiepileptic drug with tricyclic structure which implies its potential cardinotxic properties, especially in acute poisoning. AIM: To evaluate some cardiovascular effects connected with CBZtoxicity and tofind the relation between them and CBZ plasma level. MATERIAL AND METHODS: 34 patients (18 males, 16 females; median age 24.5) hospitalized in our Department in 1996-1997 and 2005-2006 due to acute CBZ poisoning. Analysis included following parameters: systolic (SBP) and diastolic (DBP) blood pressure, ECG parameters: heart rate (HR), duration of QRS complex, PQ interval and corrected QT interval (QTc) calculated with Bazett's (QTc(B)) and Hodges's (QTc(H)) formulas. These parameters were compared with reference values for general population available in the literature. Relations between above mentioned parameters and CBZ plasma level were studied by means of Generalized Additive Model (GAM). RESULTS: The reference values were exceeded most often for QRS (62%), DBP and QTc(B) (53%, both) and SBP (50%). The mean number of parameters with exceeded norms was 3.1 per patient (SD = 1.71). We failed to find any significant correlation between CBZ plasma level and any of the studied parameters. Positive correlation between SBP and DBP (r = 0.68; p < 0.001) and negative correlation between QRS and HR (r = -0.50; p = 0.003) were found. CONCLUSION: CBZ could affect different cardiovascular parameters which should be monitored in cases of acute drug poisonings. PMID- 17724879 TI - Hospital lethality in acute poisonings in the toxicology clinic of emergency medicine Institute 'Pirogov' for the period 2001-2005. AB - Acute poisoning is a sudden and potentially life threatening damage of human health, characterised by quick dynamics and high lethality. The death rate and the lethality from acute poisonings vary between countries and depend on the complex action of various medico-social factors. We have studied the hospital lethality from acute exogenous intoxications in the Toxicology Clinic of Emergency Medicine Institute "Pir ogov", Sofia, Bulgaria for 5 years period--2001 2005. We have monitored the lethality according to age and types of poisonings, as well as its relationship to the length of hospital stay and the complications occurred. The data from the other two Toxicology Departments in the country have also been taken into consideration in the analysis of the figures. The main reasons for the unfavourable outcome as well as the patients with the highest risk are analysed. Measures for diminishing of hospital lethality are discussed. PMID- 17724880 TI - [The assessment of albumin liver dialysis--MARS efficacy in the treatment of Amanita phalloides poisoning]. AB - Fourteen patients were included to the albumin dialysis--MARS in the Clinic of Internal Medicine Geriatry and Clinical Toxicology in the years 2004-2006 because of acute intoxication with Amanita phalloides. The 26 procedures were done. Ten patients recovered, one was transplanted and three patients at the age from 68 to 79 (average 72.6) years died because of acute liver failure (21.4% cases). All deceased patients had significant higher plasma bilirubin level and INR in compare to other probants. The procedures of albumin dialysis caused significant lowering of blood glucose level, red blood cells and platelets, but without the need for intervention. PMID- 17724881 TI - [Imbalance of oxidoreductive status in suicidal antidepressant drugs poisoning]. AB - The aim of this study was to examine the association between suicidal poisoning with antidepressants and the oxidoreductive balance by evaluation of changes in activity of glutathione reductase (GR) and total antioxidative status (TAS) in serum. GR activity and TAS were determined in 29 patients hospitalized after suicidal poisoning with antidepressants and compared with the results of the control group consisting of 16 healthy people. For this purpose, RANDOX diagnostic sets were used. The GR activity and TAS were significantly lower in the examined group, compared with the control group. The results obtained show a significant reduction of GR activity and TAS level in patients with suicidal antidepressants poisoning. It seems, that the oxidoreductive balance is shift towards the oxidative potential and leads to the decrease of the organism's antioxidative potential, which is manifested by the increase of oxygen free radicals and the intensification of the oxidative stress. PMID- 17724882 TI - [An assessment of cigarette smoking, with the usage of cotinine level, on life satisfaction in patients with coronary heart disease]. AB - The aim of the study was to evaluate the impact of smoking, verified by the measurement of cotinine levels, on life satisfaction of patients with coronary artery disease. The questionnaire was answered by 36 patients (26 men and 10 women) aged from 48 to 7.6 (mean 63.5) years. The questions regarded the current attitude toward smoking, subjective self-assessment of health and life satisfaction while smoking and after cessation. Cantril's ladder has been used among others to assess life satisfaction. In order to verify the answers regarding current smoking cotinine (nicotine metabolite) serum, urine and saliva levels have been measured. There were 38.8% of current smokers in the studied group of patients after PTCA. The fact of current smoking was negated by 19.4% of smokers during medical exam. Objective verification of smoking is necessary in questionnaire studies on tobacco consumption. Measurement of cotinine in body fluids (serum, urine, saliva) may be useful in these cases. After cessation of smoking 93.9% respondents reported major subjective improvement in self assessment of health. 54.5% of smokers admitted having been ashamed of the habit, and 60.6% the feeling of disturbing others while smoking. The increase of general life satisfaction measured by Cantril's ladder was observed in 94.7% of responders after cessation of smoking. PMID- 17724883 TI - [Determination of fentanyl, atropine and scopolamine in biological material using LC-MS/APCI methods]. AB - In this paper methods for determination of fentanyl (FL) and its three analogues: alfentanyl (AL), sufentanyl (SL) and remifentanyl (RL), atropine (AT) and scopolamine (SK) in biological material (whole blood and urine) using liquid chromatography atmospheric pressure chemical ionisation mass spectrometry technique (LC-MS/ APCI) are presented. Separation of analytes was performed in gradient conditions, using a LiChroCART LiChrospher 60 RP-select B column. The mobile phase consisted of 0.1% (v/v) formic acid in water and in acetonitrile. Target analytes were isolated from biological matrices using liquid-liquid extraction technique with n-butyl chloride or diethyl ether as extraction solvents. The validation data of the methods were: limit of detection (LOD, S/N = 3) and limit of quantification (LOQ, S/N = 10) - 0.05 and 0.25 ng/ml for FL, and 0.7 and 0.9 ng/ml for AT, both in blood, whereas 1.9 and 2.1 ng/ ml for FL, and 0.6 and 0.9 ng/ml for AT in urine. Calibration curves showed linearity in concentration ranges from LOQ to 25 ng/ml in blood and from LOQ to 50 ng/ml in urine. Determination coefficients (R2) of linear regression equation were higher then 0.98. Extraction recovery, intra-day precision (CV(w.g.)) and inter-day precision (CV(m.g.)) were determined at analytes and internal standard (I.S.) concentration of 5 ng/ml for blood, and at analytes and I.S. concentrations of 20 and 5 ng/ml, respectively for urine. Extraction recovery ranged from 76 to 100% for blood and 53--72% for urine. CV (n=5) and CV(m.g.) (n=15) equal from 4.8 to 7.5% and from 6.8 to 16.2% respectively for blood, and from 4.3 to 5.4% and from 5.8 to 9.5% for urine. The application of elaborated methods of the determination of FL, AT and SK in blood and urine for 8 expert opinions elaborated at the Institute of Forensic Research in Krakow is described. FL was detected and quantified in 3 cases, whereas AT and SK in 7. PMID- 17724885 TI - [Epidemiological analysis of cases with confirmed presence of amphetamine and THC in the material of Department of Analytical Toxicology and Drug Monitoring UJ CM]. AB - The aim of this paper is epidemiological analysis of poisonings with amphetamine and tetrahydrocanabinols (THC), particularly in three aspects: (1) co-occurrence of other substances (mixed poisonings); (2) factors shaping dynamics in number of poisonings and 3) average age of patients. The data this paper is based on come from the data set "Duch" which is run by the Department of Analytical Toxicology and Drug Monitoring UJ CM in Krakow. The data were collected between 1 Dec. 2001 and 28 Feb. 2005 (1186 days). Amphetamine and THC were determined in patient's urine in semi-quantitative manner by means of EMIT and FPIA methods. RESULTS: Amphetamine: In the studied period amphetamine was confirmed in 493 patients. Other substances were confirmed in 57.6% of patients: opiates--28.6% THC--14.2%, opiates and THC--5.9%. Since the beginning of the studied period till mid Aug 2003 daily number of cases showed increasing trend (0.062% per day), then the tendency was reversed (-0.074% per day). We observed more males than females (3.24:1). Most cases were poisoned on Mondays, less during the week and least on weekends. At the beginning of the studied period males were older than females (27 vs. 20 years). As the time progressed average age of males was stable but in women average age was increasing at the rate 0.004 year per day. As a consequence of this trend in winter 2004/2005 average age of both sexes was equal. THC: We observed 410 cases with confirmed presence of THC in urine. Other substances were confirmed in 40.2% of patients: amphetamine 17.1% amphetamine and opiates 7.1, opiates 7.1%. There were 17 various substances accompanying THC. In our material the sex ratio was biased toward males (7.8 to 1). Weekly dynamics of poisonings with THC have the same pattern as the one observed in amphetamine. At the beginning of the studied period males were older than females (28 vs. 20 years). Changes in averages followed the same pattern as in amphetamine. PMID- 17724884 TI - [Hazard for human health and life by unintentional use of synthetic sibutramine, which was sold as Chinese herbal product "meizitanc"]. AB - Problem of adulteration of herbal medicines with synthetic drugs is getting a common and dangerous phenomenon in Poland. The purpose of this study was the qualitative estimation of content of the Chinese herbal medicine for slimming "Meizitanc" as well as the estimation of hazard for human health and life. Twenty herbal packages which were secured by police in the 2006 year were investigated. The main ingredient of herbal medicine "Meizitanc" was sibutramine. The average mass of sibutramine hydrochloride in the "Meizitanc" capsule was about 10 mg. Additionally the trace amount of xylene and a starch were detected in the capsules. The presence of mentioned above substances were confirmed by different analytical methods like: gas chromatography with mass spectrometry GC/MS, thin layer chromatography TLC, high-pressure liquid chromatography HPLC/UV-DAD and infrared spectrometry IR. There were not determined any herbal-originated substances, which were mentioned on the packages. It was not found any pharmacologically active substance in one of the twenty examined packages. CONCLUSIONS: The medicine containing sibutramine should be used under the strict medical control. For safety of the patients all herbal products should be buy from authorized her PMID- 17724886 TI - [The most important clinical interactions among medicines used in cardiologic practice]. AB - This article presents a review of the most important (from the cardiologic practice point of view) interactions among medicines administered to the patients suffering from cardiovascular diseases, in particular among medicines with cytochrome P450 (and its isoenzymes) dependent metabolism. Cardiovascular patients, often advanced in age, usually affected by concomitant diseases and compelled to take many different medicines are particularly exposed to side effects dependent on these interactions. The article describes both beneficial and unprofitable interactions among medicines administered in cardiology. PMID- 17724887 TI - [Hymenoptera stings]. AB - Hymenoptera are the large group of insects which includes honey-bees, bumble bees, paper wasps, hornets, ants. Female hymenoptera possess specialized stinging apparatus with which they inject their venom into prey's or intruder's body. It could be life-threatening for people sensitive to the venom. The hymenoptera venom consists of mixture of biologically active substances, eg. enzymes (phospholipases, hialuronidase), peptides (melittin, apamin, mastoparans, bombolitins) and low-molecular-weight compounds (biogenic amines, acetylcholine, carbohydrates, lipids, free amino acids). Several types of reactions are possible to develop after stinging by hymenopteran insects: (1) non-allergic local reaction (pain, small oedema, redness at the site of the sting); allergic reactions: (2) large local reaction (extensive local swelling, exceeding 10 cm, persisting longer than 24 hours) and (3) anaphylaxis (generalized urticaria, bronchospasm, hypotension, cardiovascular collapse, loss of consciousness); (4) systemic toxic reaction (oedema, vomits, diarrhoea, headache, hypotension, seizures, altered mental status); (5) unusual reactions (cardiac ischaemia, encephalomyelitis et al.). Therapeutic management after stings includes removing of the stinger (bee stings), local remedies (ice-packs, topical steroids) and prevention and treatment of an anaphylactic shock (epinephrine, general steroids, beta-mimetics, fluid resuscitation, oxygen therapy). In the present review types of reaction after hymenoptera stings were described with special interest of anaphylactic and toxic reactions as well as therapeutic management after stings. PMID- 17724888 TI - [Withdrawal syndrome complicated with heart left ventricle dysfunction in young woman addicted to alcohol]. AB - A case of 23-years old woman, addicted to alcohol and affected by depression, with functional heart disturbances is described. The heart left ventricle dysfunction developed after alcohol withdrawal. In ECG leads (V2-V6, I, II, aVL) symmetrical, negative T waves were present. Echocardio graphy revealed decreased left ventricle ejection fraction (LVEF=35%) and local abnormal contractility. The cardiomyocytes necrosis markers (CK-MB, troponin I) were negative. After several days the improvement of the heart function was observed (LEVF= 56%, improving of myocardium regional contractility). The rest scintigraphy of the heart (99mTc MIBI GSPECT) was performed and its results corresponded with echocardiography revelations. The ECG changes improved during three weeks hospitalization, but were not normal on discharge. PMID- 17724890 TI - [Effective intracavitary pacemaking for Taxus baccata-induced cardiac conduction defects and arrhythmias]. AB - Case of suicidal intoxication following ingestion of approximately 120 leaves is presented. Cardiogenic shock, severe cardiac arrhythmias and conduction defects were observed in the course of intoxication. Authors believe that application of transient intracavitary pacemaking significantly contributed to patient recovery. PMID- 17724889 TI - [The application of 4-aminopyridine in calcium channel inhibitors acute poisoning]. AB - Calcium channel inhibitors have been extensively used to treat arterial hypertension, ischaemic heart disease and supraventricular rhythm irregularities. The poisonings by that category of drugs are extremely dangerous, particularly when accompanied by intoxication with other drugs affecting the circulatory function. This paper reports 3 cases of poisonings with calcium channel inhibitors (verapamil and diltiazem) in combination with angiotensin convertase inhibitors and nonselective beta-adrenolytics. Circulatory insufficiency and cardiac rhythm abnormalities were noted in all reported cases, in one in the form of ventricular bigeminy and two episodes of ventricular fibrillation, while in the two other cases in the form of 1 degree atrioventricular block. The persisting hypotonia combined with heart rhythm disturbances could not be prevented by the typical conservative treatment involving intravenous administration of infusion fluids, calcium formulations, catecholamines and atropin. The application of 4-amino-pyridine (Pymadin) caused that arterial tension and heart rate were higher, and the heart rhythm disturbances disappeared. The reported cases suggest a beneficial effect of 4-aminopyridine used to treat cases of poisonings by calcium channel inhibitors; however, up to the present time, no detailed procedures have been determined for 4-aminopyridine administration in cases like those reported above. 4-aminopyridine has not been included in the list of the antidotes approved by the WHO and, therefore, broader tests and more clinical observations are required to confirm its therapeutic value. PMID- 17724891 TI - [Severe bencyctane intoxication--a case report]. AB - Bencyclane relaxes smooth muscles of vasculature and has been used in the treatment of peripheral and cerebral circulation disorders. Bencyclane penetrates the blood brain barrier and may evoke various adverse central effects, such as psychotic episodes, coma, and convulsions. It also decreases arterial pressure by vasodilatation and has negative inotropic action. The cardiodepressive action of bencyclane is caused probably by a direct calcium-channel antagonistic mechanism. The case of a 23-year old man, addict on amphetamine, who ingested 5 g of bencyclane (Halidor) is presented. The patient developed coma, convulsions, shock and cardiogenic pulmonary edema. He required mechanical ventilation, treatment with pressure amines (dopamine and dobutamine) and calcium. The circulatory and respiratory insufficiency persisted to the seventh day of hospitalization, then the patient was completely recovered and confirmed suicidal ingestion of 50 tablets a 100 mg of Halidor. In cases of severe bencyclane intoxications most important is an intensive symptomatic treatment. In these cases extracorporeal methods of toxin elimination from the blood are probably completely inutile, because of large bencyclane volume of distribution. PMID- 17724892 TI - [Extended suicidal poisoning with carbamazepine and phenothiazine derivatives]. AB - Two cases (woman and man) of the extended suicidal poisonings with carbamazepine and phenothiazine derivatives are presented. Drug's blood concentrations during poisoning were monitored. We examine correlation between patient's general status and the drug's blood concentrations, carbamazepine and phenothiazine derivatives interaction due to young, healthy people who received no earlier treatment. MATERIAL AND METHODS: blood samples for toxicological examinations were collected at 0, 12, 24 and 48 hours after admission. Carbamazepine was determined using FPIA method and phenothiazines derivatives by HPLC-DAD. The highest blood concentrations were for carbamazepine: 30.92 mg/l (woman) and 20.95 ng/ml (man); for phenothiazine derivatives: 927 ng/ml (woman) and 733 ng/ ml (man). CONCLUSIONS: In both cases severe central nervous depression was observed due to summed action of the drugs. Sex and individual differences in cytochromes activities should have influence to carbamazepine metabolism and faster elimination time in woman. In the case of phenothiazine derivatives faster elimination time in man was observed. The differences in elimination times between compared drugs confirm their different metabolic routes. PMID- 17724893 TI - [Tiagabine overdose--report of two cases]. AB - Tiagabine is a derivative of nipecotinic acid used in the therapy of partial seizures, partial seizures with secondary generalization, stress disorder, psychosis and cocaine dependence. The pharmacologic effect of the drug is achieved by inhibition of reuptake of gamma aminobutyric acid (GABA) into glial cells and neurons, without permanent increase in whole brain GABA concentration. Symptoms of acute tiagabine overdose include seizures, coma, respiratory depression ' and less often dystonias, involuntary movements, somnolence, agitation, tachycardia and increase or decrease of blood pressure. Two cases of acute tiagabine overdose have been described in the paper presenting with partial and generalized seizures which were managed with benzodiazepines. CONCLUSIONS: The onset of symptoms of acute tiagabine overdose is rapid with resolution within first 24 hours from exposure. Acute tiagabine poisoning may present with a wide variety of neurological symptoms. Administration of benzodiazepines may improve the outcome of overdose. PMID- 17724894 TI - [Acute intoxication with zaleplon--a case report]. AB - There has been little data in the medical literature about intoxication with a new hypnotic agent zaleplon. The zaleplon, chemically N-[3-(3-cyanopyrazolo[1,5 a]pyrimidin-7-yl)phenyl]-N-ethylacetamid, is a selective agonist of the benzodiazepine omega 1 receptor subtype. The case of a 15-year-old female who eat 60 mg of zaleplon (1.2 mg/kg) because of suicidal attempt was described. At the admission to the hospital the somnolence, blurred speech, slowdown, ataxia, tachycardia and hypokalaemia were observed. The child was treated symptomatically, and discharged from the hospital for further psychologic treatment after 36 hours. CONCLUSIONS: Acute intoxication with zaleplon had mild clinical course. The signs of intoxications were drowsiness, blurred speech, ataxia, tachycardia, dizziness, confusion and vomiting. The described case required only symptomatic treatment. PMID- 17724895 TI - [Acute intoxication with clonidine--a case report]. AB - The case of a 24-year-old female who ingested 45 tablets of clonidine (Iporel a 0.075 mg) in the total dose of 3,375 mg in suicidal attempt was described. At the admission to the hospital the patient had complained of drowsiness and weakness. She was conscious but somnolent. Minimal blood pressure was 90/50 mmHg. The patient was treated with gastric lavage and crystalloids infusion. During two days of observation the symptoms were rapidly retreated. PMID- 17724896 TI - [Haemobilia in the course of acenocoumarol overdosage in patient with cholelithiasis--case report]. AB - Haemobilia is a rare cause of acute upper gastrointestinal bleeding and is often associated with a history of hepatic or biliary tract injury, tumor growth, hepatic artery aneurysm, cholecystitis, or hepatic abscess. We report a case of a 79-year-old women with haemobilia due to acenocoumarol overdosage. She has been, taking 12 mg acenocoumarol by mistake for 5 days before admission because of atrial fibrillation. INR was 20 during an admission. Ultrasonographic evaluation demonstrated hepatomegaly, cholelithiasis, thick sludge in gallbladder represented blood clots and also dilated biliary tract. Cholecystectomy was carried out. The cut section of gall bladder showed stone, haemolysed blood and blood clots. Choledochotomy showed only blood clots within the duct. The treatment lasted long period and patient died because of multiorgan insufficiency in the course of sepsis. PMID- 17724897 TI - A cocaine-associated quadriplegia and motor aphasia after first use of cocaine. AB - A 31-year-old female who have snorted one "line" of cocaine hydrochloride (approximately 35 mg), for the first time in her life, was admitted to the hospital because of acute onset of right hemiplegia and left hemiparesis evolving into quadriplegia. Motor aphasia, right eye-ball divergent strabismus and right mouth recess lowering were also observed. CONCLUSIONS: A first time mucosal administration of cocaine hydrochloride even in low dose can cause severe neurological complications like quadriplegia and aphasia. Cocaine-associated stroke can be a diagnostic problem in the emergency room. Unconscious patients or those with acute onset of neurological disorders can form a real diagnostic challenge, especially when there is no evidence of previous drug taking. PMID- 17724898 TI - [Carbamazepine hepatoxicity--a case report]. AB - An acute liver damage with jaun. dice and biochemical abnormalities developed in 16-year-old adolescent, affected by chronic hepatitis B, after 3 years of carbamazepine therapy. The maximum bilirubin concentration in the blood was 445 micromol/L and the highest activity of AST, ALT, PA, GTP were noted, 648 U/L, 1497 U/L, 312 U/L, 85 U/L respectively. INR was 1.59. The blood ammonia level was elevated to 60.9 micromol/L. The carbamazepine treatment was stopped and laboratory parameters improved. PMID- 17724899 TI - [Drug-induced liver failure caused by thiamazole and methimazole--a case report]. AB - Drug-induced liver injury might be responsible for 1 of 600 to 3500 of all hospital admissions. About 2-3% of all drug adverse effects may be connected with the liver. There could be pure injury of heaptic cells or impairment of hepatocellular bile secretion. In our case there was cholestatic liver injury after the use of thiamazole with the complete regression after the discontinuation of the drug. For two years' the patient was treated with methyltiouracyl without any side effects. After 19 years, because of thyreotoxicosis, the methimazole was used. The acute cholestatic liver injury with the high serum bilirubin level (41.4 mg/dl) was observed. Despite the discontinuation of the drug the patient was deceased. CONCLUSIONS: There are possible cross reactions among imidazolines in patients who are predispose to develop drug-induced liver failure. The doctors should pay much more attention to possible drug side effects. PMID- 17724900 TI - [Acute suicidal carbofuran poisoning--case report]. AB - A case of 49 years old woman with acute, severe suicidal carbofuran poisoning is described. The lowest activity of AChE was 0 IU/L. Because carbamates lead to multiorgan damages, especially affect central nervous system, computer tomography of the brain (CT) and examination of regional cerebral blood flow (99mTc-ECD SPECT) were done. No pathological changes were found in CT. 99mTc-ECD SPECT performed on 14th day of hospitalization, revealed disturbed regional cer- ' ebral flow generally in frontal and occipital lobes. Results of neuropsychological examination were pathological too. PMID- 17724901 TI - [Oral intoxication with xylene--a case report]. AB - A case of a suicidal oral exposure to xylene has been described. A 33 year-old female ingested 300-500 ml of xylene 2.5 hours before admission to the hospital. Hypotonia, metabolic acidosis, diarrhea and moderate, transient dysphagia were observed. Concentrations of xylene, toluene and ethylbenzene in blood at admission were 11.7; 2.9 and 0.18 mg/l respectively and 1.1; 0.33 and 0 mg/l after 24 hours after therapy. CONCLUSIONS: The course of acute xylene intoxication in the described case was relatively uneventful despite high blood concentration of xylene. Further study is necessary to establish the potentially lethal blood concentration of xylene. PMID- 17724902 TI - [Sodium azide--clinical course of the poisoning and treatment]. AB - Sodium azide poisonings occur very rarely. The mechanism of sodium azide toxic effect has not yet been fully explained. Despite the lack of an explicit procedure for the cases of sodium azide poisonings, in vitro tests and rare case reports suggest that treatment with antidotes for cyanide poisoning victims can be effective. This study describes two cases of suicidal sodium azide ingestion. Case 1. 30-year-old male ingested ca. 180 mg of sodium azide. On admission to hospital, within 4 hours from poisoning, the man complained of dizziness and anxiety. Physical examination revealed horizontal nystagmus, flapping tremor, HR 135/min. In laboratory tests, higher blood concentration of lactates (3 mmol/l) was detected, as well as lower potassium concentration (3.4 mmol/L) and increased transaminase activity (ALT 74 U/l, AST 90 U/l). Electrocardiographic tests showed a negative T wave in limb lead III. Other results were within normal. As the patient ingested a toxic dose of sodium azide, he was treated according to the therapy prescription for cyanide poisoning (amyl nitrite inhalation followed by intravenous administration of sodium nitrite and sodium thiosulphate). ECG record of the last day of hospitalization (7th day of treatment) showed negative T waves in lead III, V4-V6. He was discharged from hospital in good condition. Case 2.23 year-old male ingested 10 g of sodium azide 1.5 hours prior to admission to hospital. At the beginning, the patient's condition was good, but it changed to critical state within the first hours of hospitalization. He developed a deep coma, respiratory and circulatory insufficiency, metabolic acidosis, cardiac dysrrhythmias and anuria. Cardiac activity monitoring showed alternating tachycardia (140 beats per minute) and bradycardia (48 beats per minute), numerous additional supraventricular and ventricular extrasystoles and sinus dysrrhythmia. Cardiac arrest (asystolia) occurred twice, the second incident with fatal outcome. The patient received supportive therapy, he was also treated according to the therapy prescription for cyanide poisoning. Circulatory disturbances observed in both cases have been described in literature as symptoms of sodium azide poisoning. However, available literature data are scarce and lack systematization, most of them coming from several decades ago. The lack of patient's consent for detailed examination of circulatory system and liver made it impossible to gather further knowledge on the subject. The efficacy of treatment with antidotes for cyanide poisoning has not been unequivocally determined for this kind of intoxication. PMID- 17724903 TI - [Acute intoxication with trichloroethylene--a case report]. AB - In a study the case of an acute intoxication following inhalant abuse of trichloroethylene vapours is presented. Narcotic effects lasting for 48 hours after exposure were seen. The patient complained of strong, polyneuropathic lower legs and feet pain lasting for 7 days. Urinary trichloroacetic acid (TCA) was monitoring. Peak urine TCA concentration reached 840 mg/L on 4 day after exposure. PMID- 17724904 TI - [Acute oral double intoxication with caustic substance--a case report]. AB - Acute oral caustic ingestion may cause serious multiorgan failure. We described a case of patient who ingested twice large amount of liquid sodium hydroxide as a suicidal attempt. According to our knowledge this is the first case report of acute oral double intoxication with caustic substance in the medical literature. Late sequela (as esophagus stricture) after caustic ingestion may lead to extreme cachexia in spite of endoscopic and surgical treatment. Dual caustic ingestion obstructs the diagnostic and treatment and worsens patient's prognosis. PMID- 17724905 TI - [Two different clinical cases of acute arsenic trioxide intoxication]. AB - This paper describes two different cases of acute suicidal arsenic trioxide intoxication. Case no 1. A 38-year-old man, alcohol abuser, who ingested 4-5 g dental paste, which corresponds to 2.2-2.7 g of pure arsenic trioxide, developed gastritis with vomiting and abdominal pain, but without diarrhea. No cardiovascular collapse or renal failure were observed. The patient developed also symptoms of central nervous system injury (minor left paresis) and transient hepatic impairment. A head CT revealed no pathological changes in the brain. Hepatic disturbance recovered in a few days and the patient could be discharged on the 12 day. Case no 2. A 57-year-old man, who ingested few grams of pure arsenic developed vomiting, abdominal pain and severe diarrhea. Cardiovascular collapse as a result of intravascular volume depletion, vasodilatation and myocardial dysfunction was observed. The patient died on the first day of hospitalization. In both cases treatment included gastric lavage, BAL therapy, haemodialysis and supportive measures. PMID- 17724906 TI - [Acute intoxication with hydrogen peroxide with air emboli in central nervous system--a case report]. AB - 54-year-old woman with brain gas emboli after an accidental ingestion of concentrated hydrogen peroxide was described. Hydrogen peroxide (H2O2) is a water soluble, caustic liquid. Exposure to concentrated (> 30-35%) hydrogen peroxide may cause cardiorespiratory insufficiency, shock, convulsions, coma, and chemical burns of skin and mucous membranes. Arterial gas embolization in central nervous system is a relatively rare complication. There are three possible mechanisms of gas embolization: persisting patent foramen ovale, pulmonary gas emboli caused by aspiration of hydrogen peroxide to the lower respiratory tract, formation of gas emboli after reaching the brain. Absence of gas emboli and cerebral infarction in CT does not exclude intoxication. Hyperbaric therapy is most effective for brain air embolism complicating hydrogen peroxide poisoning in acute phase. Some authors suggested that this therapy is also effective if administered during the subacute phase. CONCLUSIONS: Neurologic symptoms after ingestion of hydrogen peroxide may suggest gas embolism of the cerebral vasculature. The absence of atrial septal defect does not exclude the possibility of cerebral air embolism. The absence of gas and cerebral infarction in CT scans does not exclude brain gas embolism. The use of hyperbaric therapy should be considered in treating severe cases of hydrogen peroxide poisoning. PMID- 17724908 TI - Heat stroke complicated by liver failure and hyperbilirubinaemia--a case report. AB - Heat stroke may appear as a result of exposure to high environmental temperature or strenuous exercise. It represents a medical emergency characterized by an elevated core body temperature and multi-organ failure. We have described a case of a 41 year-old female after sun exposure, who was admitted to the hospital with the temperature of 42 degrees C. Because of high plasma bilirubin level the Molecular Adsorbent Recirculating System (MARS) was started. Three sessions of MARS, which lasted for eight hours each, were conducted on 15h, 18th, and 23rd day of hospitalization. The procedure was well tolerated by the patient and resulted in a sustained decline of plasma bilirubin from 33.5 to 14.7 mg/dl. The female was discharged from the hospital in good general condition. The two months follow up showed that the patient felt very well, and the plasma bilirubin was reduced to 2.2 mg/dl. PMID- 17724907 TI - [Amanita pantherina poisoning or brain stroke?]. AB - A case of a 72-year-old female who ingested panther cap (Amanita pantherina) was presented. During the ingestion of mushrooms she developed short-time diarrhea and severe transient neurological disorders; short-term hallucination followed by deep coma, skeletal muscle flaccidity with hyporeflexia. Also significant facial asymmetry was noted. A head CT showed a small ischaemic focus in capsula interna. After a neurological consult it was concluded that this small malformation was not the cause of severe patient's condition. The sporological test revealed numerous spores of panther cap in patient's vomit. After the next 6 hours complete resolution of neurological symptoms was observed. Finally it was assumed that patient's symptoms and signs were most probably a result of panther cap poisoning complicated with transient ischaemia of the brain. PMID- 17724909 TI - [Side effects after the usage of Chinese dieting product Meizitanc]. AB - Side effects of self-treatment of eight obese women aged between 28 and 45 (average 36.5) with the body mass index (BMI) between 28 and 32 (average 30) kg/m2 have been described. All these women, without any medical consultation and upon their own will had been using Meizitanc as the only remedy for slimming. They started with a dosage of 1 capsule per day, gradually increasing the Meizitanc dose to 3 capsules a day. The patients had used the drug from 2.5 to 6 (average 3.2) months. There were many side effects observed in all women like palpitation, headache and vertigo, warm feeling, nervousness, and tremor of the hands which was observed in four patients. All these effects appeared during the last few weeks and thus forced them to get the consultation in the Poison Information Centre in the Medical University of Gdansk. All capsules were examined with the use of gas chromatography and mass spectrophotometer GC/MS. It was found that each capsule contained 10 mg of sibutramine. There was no information about the presence of sibutramine in the composition of Meizitanc on the package and leaflet. After discontinuation of Meizitanc all side effects disappeared. CONCLUSIONS: Special caution is advised during the Meizitanc treatment. In case of any side effects like palpitation, headache and vertigo, nervousness or tremor which take place during the Meizitanc treatment the medical consultation is needed. PMID- 17724910 TI - [Diagnostic difficulties in foodborne botulism--case reports and literature review]. AB - Food borne botulism is a relatively rare clinical syndrome, which symptomatology is generally highly distinctive. The physicians of various specialties should be familiar with the symptoms of botulism because its sings concern the nervous system, the organ of sight and the gastrointestinal system. In older persons with coexisting chronic diseases some symptoms of botulism may be not distinctive or may mimic exacerbation of early existing diseases. The handbook descriptions present the food borne botulism as dramatic and often deadly disease. However in some cases this disease can have mild course and poor symptomatology. Two cases of food borne botulism with different clinical course are presented in this paper, when the correct diagnosis was established with delay. A 78-year-old man was admitted with the symptoms of pneumonia and dizziness of uncertain aetiology. The diagnosis of food borne botulism was established in 10th day of hospital stay, when the most symptoms were not present. Despite of such late diagnosis and relatively good patient's condition a therapy with antitoxin was administrated. The second case reports a 70-year-old man with chronic heart failure, diabetes and obesity, when the delay of correct diagnosis was about of 24 hours. Despite of relatively early antitoxin administration and intensive supportive care patient died in 11th day of hospital stay. PMID- 17724911 TI - [The clinical experience with MARS and Prometheus procedures]. AB - Based on the hypothesis, that extracorporeal removal of endo- and egzogenic substances should be beneficial to the clinical course of the patient in liver failure or poisoned, treatment systems were evaluatedbased on the two concepts: (1) blood dialysis against albumin dialysate--Molecular Adsorbent Recirculating System (MARS), Single Pass Albumin Dialysis (SPAD), Continuous Veno-Venous Haemodiafiltration (CWHDF); (2) selective albumin filtration and adsorption combined with haemodialysis--Fractioned Plasma Separation and Adsorption Prometheus. We present our own experiences with MARS and Prometheus procedures between 2003-2006 years. PMID- 17724912 TI - Suicidal attempt of a schoolgirl to demonstrate against the school teacher and try to make her quit the school. AB - A case of a 16-year-old schoolgirl who had admitted a demonstrative suicide attempt against her school teacher thus trying to make the teacher leave the school has been presented. During the observation period in the Emergency Department the nurse taking care of the patient overheard that during her talks with the friends, the girl had been continuously urging them to swallow the same set of tablets, call the ambulance and get admitted to the hospital. The anamnesis revealed that three schoolmates decided to get rid of one of the teacher from their school by accusing her of mental cruelty which had led them to suicidal attempts. It was done mainly because of the bad marks they had got from the teacher. The idea was undertaken by our patient due to many news transmitted in the newspapers and television during last months in which the teachers were blamed for a lot of incidents which had taken place in different schools in Poland. Despite the fact that in many of these events the teachers were both physically and mentally tormented by the pupils the opinions presented by mass medias were always against them. Our patient said that in such circumstances it was supposed to be an easy way to solve all the problems with unlike teacher. CONCLUSIONS: The physicians should pay more attention on suicidal attempts causes specially in adolescents. Adolescents possess poor knowledge of the lethal potential of drugs, specially over-the-counter medications. The media have to take more responsibility for transmitting news concerning youth which should be more honest and verified. PMID- 17724913 TI - [Drug counterfeiting--the risk to the public health]. AB - Pharmaceutical counterfeiting and purchasing medicines from illegal distribution channels have become more and more common problem in our country. Different medicines, especially erectile dysfunction drugs are involved. The aim of this study was the qualitative analysis of fake Levitra tablets and the estimation of the risk they bear to potential users. Tablets were secured by the police and delivered to Bayer office in 2006. RESULTS: Trace amount of sildenafil (the active ingredient of Viagra) and not vardenafil (the active ingredient of Levitra) was found in tablets described as "Levitra" (vardenafil). The presence of this substance was discovered by NIR--and Raman spectroscopy. The appearance of tablets and blisters corresponded to the original product. There were no paper boxes and patient information leaflets attached. As prescription medicines erectile dysfunction drugs should be purchased from a pharmacy only. They need to be used under strict medical control. PMID- 17724914 TI - [Heme oxygenase as a potential therapeutic target for hepatoprotection]. AB - Heme oxygenase (HO) is the rate limiting enzyme in the breakdown of heme into carbon monoxide (CO), iron and biliverdin. To date three mammalian HO isozymes have been identified, and only one of them (HO-1) is inducible. The products of HO-catalyzed reaction, particularly CO and biliverdin/bilirubin have been shown to exert protective effects in the liver against different noxious stimuli. The results of experimental data show that induction of HO-1 expression contributes to protection against liver damage induced by several chemical compounds such as acetaminophen. PMID- 17724915 TI - [The role of intestine in detoxification]. AB - In the result of liver detoxification, xenobiotics change into more water soluble and thus easier for excretion from the body. It is convenient to consider this process as occurring in two phases. In phase I, the major reactions involved are hydroxylation, catalyzed by monoxygenases. In phase II, the preliminary modified xenobiotics after conjugation with some specific metabolites are transformed into less toxic and more soluble end-products. Recently, antiporter activity of MDR1 (MultiDrug Resistence) gene products in enterocytes was recognized as important stage in detoxification of xenobiotics, and definied as phase III of this process. PMID- 17724916 TI - [Perspectives of inhaled insulin treatment]. AB - In the article some merits and some limitations of inhaled insulin (Exubera produced by Pfizer) in the treatment of adult patients with type 1 or 2 diabetes were presented. Up till now about 3500 volunteers usually in short-term study periods (6 months) were examined. Some patients were observed in the course of treatment even 4-7 years. Inhaled insulin was well tolerated by patients and they accepted with satisfaction this new form of drug. Main adverse events were a small decrease in the forced expiratory volume at 1 s (FEV1) and a small decline in carbon monoxide diffusion capacity with no clinical significance a well as a mild or moderate cough occurring temporally. Inhaled insulin is contraindicated in smokers and patients with bronchial asthma, bronchitis and pulmonary emphysema. Despite the approval of inhaled insulin for use in adult patients with type 1 or 2 diabetes in the United States and European Union in January 2006, Pfizer designed Real World Trial to estimate the costleffectiveness of this drug and the effect of the availability of Exubera as a treatment options for glycemic control. PMID- 17724917 TI - [Insulin resistance in type 2 diabetes patients]. AB - Among 1052 type 2 diabetics 11 patients with insulin requirement from 102 to 138 (average 123) i.u. were selected. They were only 1% of the population. Two of them (average age 49,5 years) suffered from diabetes 4 and 6 years, had BMI 26-27 kg/m2 and were free of other metabolic syndrome manifestations. Nine patients (8 women and one man) with average parameters--62 years-old, diabetes duration 15.7 years, BMI 34,7 kg/m2 suffered from metabolic syndrome and its complications such as ischemic heart disease and/or state after stroke. The attempt of treatment 7 patients with metformin (2550 mg/24h) for 3-4 months has not caused significant decrease of daily insulin requirement. PMID- 17724918 TI - [No influence of imatinib on type 2 diabetes]. AB - Five patients with type 2 diabetes, three of them treated with insulin and two with oral antidiabetic drugs, receiving imatinib due to chronic myeolid leukaemia are reported. Treatment with imatinib 400 mg/day for 7 to 37 (mean 24.2) months had no positive effect on clinical course of type 2 diabetes. PMID- 17724919 TI - [Late recurrence of malignant tumours 20 years after diagnosis and treatment]. AB - Late recurrence of malignant tumours is very rare phenomenon. Seven cases of late recurrent malignancy (melanoma--2 cases, clear cell renal cancer, stomach sarcoma, breast cancer, basal cell carcinoma, ovarian cancer) after 20-32 (average 22.3) years from diagnosis and treatment were described. The histopathological examination results of primary and recurrent tumours were identical. Six patients died at the age from 40 to 89 (mean 66.8) years. The survival of patients after recurrence was from 4 to 11 (mean 7.3) months. PMID- 17724920 TI - [Tobacco smoking and multiple primary cancers]. AB - Seventy six patients (55 males and 21 females) aged from 39 to 89 (mean 63.7 +/- 9.7) years with multiple primary cancers were described. Larynx cancer was the most commonly seen multiple primary cancer component (35.5%) followed by lung cancer (12.5%). Combination of larynx cancer and lung cancer was the most often observed connection (21.1%). In seventeen patients two cancers were diagnosed concurrently. In other cases the interval between two cancers varied from 1 to 24 (mean 6.9 +/- 6.1) years. Smoking rate was 80.3% at diagnosis of the second cancer and only 10 patients (13.1%) quit smoking when first cancer was recognized. The results of the research indicate the necessity of conducting wide prophylactic actions. PMID- 17724921 TI - [The assessment of age-standardised cancer incidence rates in the chosen organ systems]. AB - Age-standardised cancer incidence rates in reproductive system, digestive system and respiratory system were analyzed taking into account the statistics for 38 States of USA (1996-2001), European Union (2006) and Europe (2006). Age standardized incidence rate in the reproductive system was higher in comparison with the corresponding rates for digestive and respiratory systems. The authors put under discussion a hypothesis of this phenomenon. PMID- 17724922 TI - [Recurrence of pheochromocytoma in the second adrenal gland 19 years after adrenalectomy]. AB - A case of the patient who underwent by bilateral adrenalectomy at the age of 37 and 56 years due to recurrent pheochromocytoma has been described. The authors stress that follow-up of patients after adrenalectomy is mandatory on lifetime basis. PMID- 17724924 TI - [Alcohol abuse by young people in Spain]. AB - Although the overall consumption of alcohol is falling in Spain we have, for years, been seeing an increase in alcohol consumption by the young. This has taken the form of episodes of drunkenness or quantities of alcohol being drunk within a few concentrated hours to reach a certain level of drunkenness, what the Anglo-Saxons call "binge drinking". The most typical name for this phenomenon although not the only one- is the botellon which is, in fact, no more than one of the expressions to describe drinking alcohol in the nighttime recreational spaces at the weekend. It is of some concern that, in conjunction with a leading position in the use of illegal drugs, Spain is also so rapidly incorporating this pattern of alcohol consumption, and one that has never formed part of our traditions. However, it does not appear that these issues are a priority for Spanish society, as has been confirmed by sociological surveys, and by the way in which the law intended to regulate alcohol consumption by minors was recently withdrawn. Diverse aspects must be taken into account if we wish to see a reversal in the current situation: the active role of the alcohol and recreation industries, the overall passive role of the professionals in alcohol and drugs in public debate, lack of determination by the authorities, the discourse in the media, the difficulty that the adult world has of taking up a position on these behaviours. Failure in not starting to act now will make it all more difficult in the future. PMID- 17724923 TI - [Spontaneous regression of cancer--review of cases from 1988 to 2006]. AB - Spontaneous regression of malignant tumours is a rare and enigmatic phenomenon. We reviewed the cases of spontaneous regression of cancer in medical literature according to MEDLINE database in the period 1988-2006 and compared them with similar reviews from 1900-1987 period. The number of reported cases of spontaneous regression increased steadily in XX century, probably due to a rising interest in this problem and new possibilities of radiological and biopsy examinations. Spontaneous regression of malignancy was reported in almost all types of human cancer, although the greatest number of cases in years 1988-2006 were reported in patients with nephroblastoma, renal cell carcinoma, malignant melanoma, lymphoma. Elucidation of the process of spontaneous regression offers the possibility of improved methods of preventing andlor treating cancer. PMID- 17724925 TI - [Caffeine: a nutrient, a drug or a drug of abuse]. AB - Coffee, tea, chocolate and caffeinated drinks are the main sources of caffeine, which is consumed in almost all ages and socioeconomic levels. Caffeine acts as a non-selective adenosine receptor antagonist in the central nervous system. Its main effects are as psychostimulant, acting in addition on the respiratory, muscular and cardiovascular systems. Basically, caffeine is metabolized by the hepatic cytochrome P-450 1A2 enzymes (CYP1A2). Several drugs can interact with its metabolism. The observed interindividual differences of its effects can be explained by variations in its metabolism. The main therapeutic use of caffeine is bronchodilator in respiratory diseases. Other possible uses are under investigation. Acute or chronic consumption of caffeine can induce several adverse effects, including intoxication that can be lethal. Finally, caffeine can be considered a drug of abuse. It has positive reinforcing actions, produces tolerance, and a withdrawal syndrome after stopping its consumption. Caffeine can cause different mental disorders such as dependence, which is not included in the DSM-IV-R, withdrawal syndrome and intoxication. Depending on its use, caffeine can be considered a nutrient, a drug or a drug of abuse. PMID- 17724926 TI - [Relation of the physical-sport activity practice and alcohol consumption of citizens older than 14 years old]. AB - The aim of the current research is to ascertain any possible relationship that could exist between the alcohol consumption of the population and several sociodemographic variables, in addition to the influence of physical exercise/sports on the creation of healthy lifestyle habits. The sample comprised 1102 subjects from Almeria Spain, over 14 years of age, to whom we administered the "physical exercise/sporting habits and life styles" questionnaire, selecting the sections on physical exercise/sporting habits in leisure, fitness and state of health perception and alcohol consumption habits, related to attitudes, behavioural and sociodemographic variables. We used an innovative tool for data analysis in the sphere of physical exercise, known as the Bayesian networks, emphasizing a positive relationship between alcohol consumption and physical exercise/sporting activities, it being the active people, with an interest in physical exercise/sports, who have a good perception of their health and physical fitness who are the ones who make habitual and occasional use of this substance. The profile of the individual who does not drink alcohol is female, over 44 years of age, with no studies, housewives who have a poor perception of their health, and who do not do any physical exercise or plays sports, whereas the populations with health risks, are men between 15 and 44 years of age who have secondary school studies or a degree and who work in the public or private sector. PMID- 17724928 TI - [Alcoholic jealousy: an old and current dilemma]. AB - The relation between alcohol and jealousy is a deeply rooted belief within the general population as well as in the medical, and particularly psychiatric, environment. Furthermore, in recent years there has been a growing interest on the forensic aspects of pathological jealousy, since they are a frequent cause of severe violence, homicide and suicide. Some authors have described a high prevalence of pathological jealousy in alcoholic patients, even awarding it a pathognomonic value in alcoholism. Nevertheless, recent studies do not completely support this relation, and draw attention to other factors. Results from the various studies contain several definitions and classifications of pathological jealousy, and although most of them highlight the prevalence of jealousy in alcoholic patients, they question its pathognomonic quality. Also, the presence of pathological jealousy in subjects with psychiatric disorders other than alcoholism is suggested, indicating the existence of predisposing and triggering factors which could explain the development of pathological jealousy. Yet, the important methodological difficulties in the published articles and the shortage of studies do not allow the confirmation of the alcoholic etiology in pathological jealousy; this is the reason why considering alcoholic jealousy as a separate entity is debatable. In this sense, the best diagnosis in these patients would be paranoid disorder combined with alcoholic dependence, hence, a dual diagnosis. PMID- 17724927 TI - [Evolution of treatment and consumption in persons with cocaine dependence, at 12 months, in respect of the associated psychopathology and daily functioning]. AB - The aim of the present study is to analyse the evolution, at 12-months, of patients with cocaine dependence undergoing treatment in drug abuse centres. We examined the relationship between sociodemographic variables, drug use characteristics, and psychopathological characteristics with maintenance of drug abstinence and the evolution of daily functioning evaluated by the therapist at 3 , 6- and 12-months. The most outstanding results are that subjects with a dependent personality pattern, according to the MCMI-II, are more likely to maintain cocaine abstinence during the 12-months following the preliminary assessment. Moreover, the variables more related with a worse daily functioning at 12-months are injected or smoked cocaine use, previous treatments for drug use and having used heroin on some occasion. Therefore, drug related aspects and not psychopathological characteristics are more important when analysing the 12 months evolution in these subjects. PMID- 17724929 TI - [Gender differences in the evolution of adolescent's tobacco consumption in Spain (1986-2002)]. AB - This work pursues two objectives: 1) to analyse time trends in tobacco consumption among Spanish schoolchildren aged 11, 13, 15 and 17 for the period 1986-2002; and 2) to study the evolution of gender differences regarding tobacco consumption in each of these age groups throughout this period. On the basis of a research with a sequential cross-sectional design, data were collected in four nation-wide studies (in 1986, 1990, 1994 and 2002), using representative samples of Spanish schoolchildren. The sub-samples used for this paper add up 14,570 subjects (51.2% girls and 48.8% boys). The analysis of temporal trends has been performed separately for each gender, within each age group. Among 11-year-olds, a growing homogeneity between genders concerning tobacco consumption has been proved, with a general trend to a decrease in the problem. Among 13-year-olds, time trends are very similar to 11-year-olds, except for the period 1994-2002, where there has been an increase in the prevalence of smoking among girls. As for the 15 and 17-year-olds, a growing differentiation between genders has been proved, with a marked rising tendency among girls in all aspects studied. Regarding boys of those ages, the situation is relatively stable since 1990. The spreading of this problem among girls will probably strengthen in the future the current trend toward an increase in tobacco consumption among Spanish adult women. PMID- 17724930 TI - [Needs satisfaction deficit among cocaine and/or marijuana users asking for treatment]. AB - As part of a pioneer investigation line on the field of addiction and mental health centred on the operationalization of clinical implications of the motivational theory of Maslow (1954/1970) and feedback treatment and prevention strategies of drug use and its associated disturbances, it is tested the psycho pathogenesis construct of this theory by means of a cross sectional design of four independent samples, on which it is explored the satisfaction degree of 16 deficitary needs on intentional samples of adolescents and young adults: Three samples of actual users of marihuana (n = 47), cocaine (n = 47) and both substances (n = 50), that were gotten between treatment solicitors and a sample of students and workers non illicit drug users (n = 150). The comparative and predictive statistical analysis provide validity to the psycho-pathogenesis construct of the theory of motivation of Maslow, and its stand out: 1)The potential utility for the treatment of the development of techniques and instruments oriented to cover the deficit of satisfaction of the needs of health, tranquillity, order, emotional security, family justice, love, friendship, respect, tenderness, power, domination, success and money and; 2) The importance for the prevention of the actual consumption of drugs as cocaine or marihuana of the development of strategies focused to keep satisfied the needs of health, tranquillity, affection, respect and success. PMID- 17724931 TI - Suicide and alcohol poisoning in Belarus between 1970 and 2005. AB - BACKGROUND: The association between alcohol and suicide is well documented. The solid body of research and empirical evidence suggests that hazardous pattern of alcohol consumption (binge drinking) lead to quicker and deeper intoxication, increasing the propensity for alcohol-related suicide. PURPOSE: To estimate the aggregate level effect of binge drinking on suicide rate. METHOD: Trends in suicide and fatal alcohol poisoning rate (as a proxy for binge drinking) from 1970 to 2005 in Belarus were analyzed employing ARIMA analysis in order to assess bivariate relationship between two time series. RESULTS: The results of time series analysis suggests close relationship between suicide and fatal alcohol poisoning rate at aggregate level. CONCLUSION: This study supports the hypothesis that suicide and alcohol closely connected in culture with prevailing intoxication-oriented drinking patterns and adds to the growing body of evidence that a substantial proportion of suicide in Belarus is due to acute effect of binge drinking. PMID- 17724932 TI - [Application of peracetic acid for the treatment of juvenile sander (Sander lucioperca) during Ichthyophthirius multifiliis infestation]. AB - White spot disease caused by the ciliate protozoan parasite Ichthyophthirius multifiliis (I. m.), is one of the most dangerous diseases in aquaculture and ornamental fish breeding worldwide. The parasite is characterized by three developmental stages: a reproductive tomont, an infective theront and a parasitic trophont. In sander (Sander lucioperca) breeding I. m. causes serious economic losses. After banning of the traditional therapeutic agent malachite green we have to face a state of emergency for the treatment of the ichthyophthiriasis in Germany. The peracetic acid (PAA), characterized by positive therapeutical properties, might close this gap. The purpose of our investigations was the determination of the toxicity of PES to juvenile sander as well as the evaluation of the therapeutic effectiveness of the substance to combat I. m. For juvenile sander (length 3 cm) we determined a 24-h-LC50 of 1.14 (0.97; 1.3) ppm PES. In two investigations PAA was applied in daily intervals of 0.5; 1, 3, 5 and 24 h and concentrations of 0.5; 1; 1.5 and 2 ppm to treat I.-m.-infection in sander. In test I all sander (length 9 cm) died as a result of the I.-m.-infection. However, the PAA exposed fish survived longer than the PES-free controls! This might be due to a disinfection of other pathogens by PAA. In test II, the fish (length 12 cm) were less infected than fish in test I. Four of six fish died in the group exposed with 2 ppm PAA for 24 hours. The abundance of I.-m.-trophonts was determined in mucus, fin and gill tissues of all fish. Significant differences could not be observed between test I and test II because of dissimilar: 1. exposure in time and concentration, 2. age and condition of the fish and 3. homogenity of the variances. Therefore, no therapy strategy was successful while fighting the parasitic trophonts protected by the overlaying fish tissues. We speculate that a successful therapy of I. m. with PAA is, as known e.g. for malachite green, only possible while fighting the free living stages theronts and tomonts. This will be part of our subsequent investigations. PMID- 17724933 TI - Hydrated sodium calcium aluminosilicate for reduction of aflatoxin in quails (Coturnix coturnix japonica). AB - The purpose of the present study was to evaluate the toxic effects of aflatoxin (AF) on growth performance and various processing parameters of quails and to determine the preventive efficacy of hydrated sodium calcium aluminosilicate (HSCAS). One hundred and eighty 1-d-old quails of both sexes were randomly divided into 4 experimental groups with 5 replicates and 45 birds following weighing. The experimental design consisted of four dietary treatments: 1) control with 0 mg AF/kg of diet and 0% HSCAS; 2) 0.5% HSCAS; 3) 2.5 mg AF/kg of diet; 4) 2.5 mg AF/kg of diet plus 0.5% HSCAS. The chicks were housed in electrically heated battery cages and exposed to light for 24 h from hatching to 3 weeks of age. Quails consumed the diets and water ad libitum. Body weight (BW) was significantly (p < 0.001) increased by addition of HSCAS to AF diet. The lowest BW gains in groups received AF alone was observed at all periods. The reduction in BW gain caused by 2.5 mg AF/kg of diet was significantly (p < 0.001) diminished by the addition of 0.5% HSCAS to the diet. The addition of HSCAS to the AF diet significantly (p < 0.001) protected against decrease of feed intake at all periods with exception of the first period. None of the treatments altered significantly the feed conversion ratio (FCR). The relative weights of the liver, kidney and spleen were increased in the chickens consuming the AF alone diet. However, light microscopic examination demonstrated the addition of HSCAS to quail feed to partially decrease fat deposition caused by the toxin, and besides, electron microscopic examination of indicated a reorganization in the endoplasmic reticulum and increase in the number of ribosomes and polisomes. Furthermore, the decrease in the antibody titre induced by Newcastle vaccine, due to aflatoxins, was relatively prevented. No significant differences were observed for serum total protein, total cholesterol and glucose levels. The results of indicate that HSCAS is effective in preventing the deleterious effects of AF. PMID- 17724934 TI - Avian influenza A viruses in birds of the order Psittaciformes: reports on virus isolations, transmission experiments and vaccinations and initial studies on innocuity and efficacy of oseltamivir in ovo. AB - Birds of the order Psittaciformes are - besides chickens, turkeys and other birds - also susceptible to infection with avian influenza A viruses (AIV) and succumb following severe disease within one week. Published data prove that various parakeets, amazons, cockatoos, African grey parrots and budgerigars (genera Barnardius, Psittacula, Cacatua, Eolophus, Amazona, Myiopsitta, Psittacus and Melopsittacus) were found dead following natural infections. Natural infections of highly pathogenic avian influenza viruses (HPAIV) of the haemagglutinin subtypes H5 and H7 cause severe disease and high rates of mortality. Experimental transmission studies with AlVs of the subtypes H5 and H7 confirm these data. Viruses of the subtypes H3N8, H4N6, H4N8, H11N6 and H11N8 may cause also clinical signs and occasionally losses in naturally infected psittacine birds. Clinical signs and losses were also noted following experimental infection of budgerigars with a H4N6 virus. In the EU and in other countries, vaccination of exposed exotic and rare birds and poultry is a possible and an acceptable measure to provide protection. Currently, the EU Commission accepts inactivated adjuvanted vaccines whereas in some other countries recently developed vector vaccines are applied. However, birds remain susceptible during the time interval between application of any vaccine and the development of immunity. This critical period can be bridged with antiviral drugs. Our in ovo studies demonstrate that the neuraminidase inhibitor oseltamivir is non-toxic for chicken embryos at concentrations of 0.1, 1.0 and 10.0 mg/kg body weight. These dosages prevented entirely the replication of a HPAIV of the subtype H7N1 when this drug is given shortly prior to, simultaneously or soon after inoculation of chicken embryos with this AIV. Thus, we speculate that exposed valuable birds such as psittacines at risk can be successfully treated. PMID- 17724935 TI - [Homeopathic prophylaxis in dairy cows on an organic farm part 1--fertility]. AB - The objective of the study was to assess the efficacy of different prophylactically applied homeopathic compounds on health and fertility during the periparturient period on an organic dairy farm. In a randomised double blinded study 146 dairy cows were enrolled in two treatment groups. The average milk yield was about 5100 kg per cow per lactation. The treatment group received the homeopathic compounds Carduus comp. and Coenzyme comp. at drying off, Traumeel on the day of calving, Lachesis comp. on day 7 post partum (p.p.) and Carduus comp. and Coenzyme comp. on day 14 days p.p. The control group followed the same protocol with a placebo (physiological saline solution). Each drug was administered subcutaneously in a dosage of 5 ml. At drying off, the day of calving and in weekly intervals until day 35 p.p. clinical examinations as well as blood sampling were performed. The effect of treatment was measured by clinical parameters, reproductive performance and serum profiles (Ca, P, AST, Urea, Bilirubin). Data of reproductive performance (days to first service, days open, conception rate) were compared between treatment groups and to those in the previous lactation. There was no significant difference between both treatment groups. Cows of the treatment group had an earlier onset of cyclic activity, especially when milk yield was considered as an influencing factor (82% vs. 57%, P < 0,05). In contrast the cows of the treatment group had a significant lower submission rate. The prophylactic treatment of all cows did not have an effect in general, but in cows with increased milk yield, especially in the current lactation. The reproductive performance in the previous lactation did not have any effects on the success of the homeopathic treatment. Reproductive performance in the herd could be enhanced slightly compared to the previous lactation. PMID- 17724936 TI - The influence of omega-3 polyunsaturated fatty acids feeding on composition of fatty acids in fatty tissues and eggs of laying hens. AB - The paper deals with supplementation of hen diet with oils with increased content of omega-3 polyunsaturated fatty acids (PUFA) and occurrence of fatty acids (FA) in fatty tissues and eggs of laying hens after the respective supplementation. The experiment was carried out on 30 laying hens of ISA BROWN hybrid, divided to three groups (A, B, C). For the period of three weeks the group A was administered flax-seed oil, group B served as a control and group C was fed base rations supplemented with fish oil. In addition to that the diet of groups A and C was supplemented with vitamin E as an antioxidant. Administration of the oils as a source of omega-3 PUFA increased their concentration in both the fatty tissues and egg-yolk which resulted in the change of the ratio of omega-6 and omega-3 PUFA. No influence of flax-seed and fish oil on concentration of alpha tocopherol in egg-yolk was observed. PMID- 17724937 TI - Clinical snapshot. Spinal epidural empyema. PMID- 17724939 TI - Clinical snapshot. Insect-bite hypersensitivity. PMID- 17724938 TI - Hypothyroidism and myxedema coma. AB - Hypothyroidism is a common endocrinopathy in dogs but is rare in cats. Lymphocytic thyroiditis and idiopathic thyroid atrophy are common causes of this condition. Specific thyroid function tests, in conjunction with clinical signs and physical examination findings, are used to help confirm a diagnosis of hypothyroidism. This disease can be managed with synthetic hormone supplementation and has an excellent prognosis. Myxedema coma is a rare and potentially fatal manifestation of severe hypothyroidism that can be successfully treated using intravenous levothyroxine. PMID- 17724941 TI - Reconstructing weight-bearing surfaces: digital pad transposition. AB - The paw pads of dogs and cats are specialized skin structures that provide cushioned, durable, weight-bearing surfaces. Otherwise normal limbs may be rendered useless when pad tissue is lost because of trauma or tumor resection. This article reviews previously described reconstructive techniques involving the movement of pad tissue into weight-bearing defects. In addition, a case series of single-stage digital pad transfer to replace all or part of metacarpal or metatarsal defects is reported. This technique was predictably successful with minimal complications in conjunction with complete tumor resection, although results in two cases of severe paw trauma were less favorable. PMID- 17724940 TI - The litterbox blues. PMID- 17724942 TI - Clinical snapshot. Uterine adenocarcinoma. PMID- 17724943 TI - The emotional impact of medical errors on practicing physicians in the United States and Canada. AB - BACKGROUND: Being involved in medical errors can compound the job-related stress many physicians experience. The impact of errors on physicians was examined. METHODS: A survey completed by 3,171 of the 4,990 eligible physicians in internal medicine, pediatrics, family medicine, and surgery (64% response rate) examined how errors affected five work and life domains. RESULTS: Physicians reported increased anxiety about future errors (61%), loss of confidence (44%), sleeping difficulties (42%), reduced job satisfaction (42%), and harm to their reputation (13%) following errors. Physicians' job-related stress increased when they had been involved with a serious error. However, one third of physicians only involved with near misses also reported increased stress. Physicians were more likely to be distressed after serious errors when they were dissatisfied with error disclosure to patients (odds ratio [OR] = 3.86, confidence interval [CI] = 1.66, 9.00), perceived a greater risk of being sued (OR = .28, CI = 1.50, 3.48), spent greater than 75% time in clinical practice (OR = 2.20, CI = 1.60, 3.01), or were female (OR = 1.91, CI = 1.21, 3.02). Only 10% agreed that health care organizations adequately supported them in coping with error-related stress. DISCUSSION: Many physicians experience significant emotional distress and job related stress following serious errors and near misses. Organizational resources to support physicians after errors should be improved. PMID- 17724944 TI - Miles to go: an introduction to the 5 Million Lives Campaign. AB - BACKGROUND: The Institute for Healthcare Improvement (IHI)'s 5 Million Lives Campaign targets a reduction of five million instances of harm from December 2006 through December 2008. The campaign continues the six interventions of the 100,000 Lives Campaign and adds six more. DEFINITION OF MEDICAL HARM AND SETTING THE GOAL: The campaign's aim is to support the reduction of medical harm, so defined: "Unintended physical injury resulting from or contributed to by medical care (including the absence of indicated medical treatment), that requires additional monitoring, treatment, or hospitalization, or that results in death." The goal of a reduction of five million incidents of harm in two years is based on an estimate that 40 to 50 incidents occur per 100 admissions, for a total of 15 million incidents of medical harm each year in the United States. THE 5 MILLION LIVES CAMPAIGN'S "PLATFORM": This campaign's six new interventions address the prevention of pressure ulcers, reduction of methicillin-resistant Staphylococcus aureus (MRSA) infection, prevention of harm from high-alert medications, reduction of surgical complications, delivery of reliable and evidence-based care for congestive heart failure, and getting hospitals' boards of directors on board. CONCLUSION: Together with complementary partner initiatives, the 5 Million Lives Campaign is intended to act as a major driver of national improvement. PMID- 17724945 TI - The continuing problem of missed test results in an integrated health system with an advanced electronic medical record. AB - BACKGROUND: Missed results can cause needless treatment delays. However, there is little data about the magnitude of this problem and the systems that clinics use to manage test results. METHODS: Surveys about potential problems related to test results management were developed and administered to clinical staff in a regional Veterans Administration (VA) health care network. The provider survey, conducted four times between May 2005 and October 2006, sampling VA staff physicians, physician assistants, nurse practitioners, and internal medicine trainees, asked questions about the frequency of missed results and diagnosis or treatment delays seen in the antecedent two weeks in their clinics, or if a trainee, the antecedent month. RESULTS: Clinical staff survey response rate was 39% (143 of 370), with 40% using standard operating procedures to manage test results. Forty-four percent routinely reported all results to patients. The provider survey response rate was 50% (441 of 884) overall, with responses often (37% overall; range 29% to 46%) indicating they had seen patients with diagnosis or treatment delays attributed to a missed result; 15% reported two or more such encounters. DISCUSSION: Even in an integrated health system with an advanced electronic medical record, missed test results and associated diagnosis or treatment delays are common. Additional study and measures of missed results and associated treatment delays are needed. PMID- 17724946 TI - Housestaff and medical student attitudes toward medical errors and adverse events. AB - BACKGROUND: A lack of formal patient safety curricula has contributed to the suboptimal training of medical students and housestaff. Attitudes of physician trainees regarding medical errors and adverse events were surveyed in a pilot study. METHODS: Five hundred sixty-three physician trainees were surveyed at an urban teaching hospital. Five domains were evaluated using a factor analysis as they relate to patient safety: knowledge, self-efficacy, awareness of safety culture, barriers/facilitators, and awareness of human factors. RESULTS: One hundred fifty-eight (28%) trainees completed the survey, with 22% (n = 35) describing exposure to at least one adverse medical event. The survey showed good internal validity and reliability. Respondents who reported exposure to adverse events demonstrated a lower awareness of human factor errors (p = .0017) and lower awareness of the hospital's approach to safety (p = .033). Older respondents scored higher on measures of self-efficacy than younger trainees (p = .042). DISCUSSION: The exposure of physician trainees to errors and adverse events can have a negative effect on their attitudes and competencies. Exposure to adverse events and the institution's response may decrease both error reporting and the willingness to adopt safety practices. The results support the need for implementing a sustained patient safety curriculum that promotes learning regarding adverse events. PMID- 17724947 TI - Awareness and use of a cognitive aid for anesthesiology. AB - BACKGROUND: The Veterans Health Administration's (VHA's) National Center for Patient Safety developed a cognitive aid to help anesthesiologists manage rare, high-mortality adverse events. METHODS: Six months after the aids were sent to VHA facilities with anesthesia machines, anesthesia providers were surveyed about their knowledge and use of the aid. RESULTS: Seven percent of respondents had used the cognitive aid in an emergency ("emergent users"). Most (87%) of respondents were aware of the aid. Half used it only as a reference ("reference users"), 30% were nonusers, and 13% of respondents were unaware of the aid. User groups did not differ regarding exposure to emergencies. All emergent users reported that it helped during an emergency, and 93% reported that it was well designed and easy to use. Emergent users were more likely than other groups to have first found out about it through formal orientation (53%; p < .001). Nonusers (46%) and reference users (38%) were more likely than emergent users (30%) and those who never saw it (5%) to have first found out about it through informal communication with a colleague (p = < 0.001). The majority of those who never saw the aid first became aware of it through this survey (71%; p < .001). The aid was used most commonly for difficult airway. DISCUSSION: A cognitive aid for use in rare emergencies proved clinically useful to anesthesia providers. PMID- 17724948 TI - Improving rapid response systems: progress, issues, and future directions. AB - "Detect the emergency and respond to it right at the patient's bedside" sums up the focus of the recent Third International Conference on Rapid Response Systems. PMID- 17724949 TI - Pollution of operating theatre atmosphere. 1976. PMID- 17724950 TI - Use of right lighting levels essential. AB - Hospital lighting must conform to a wide range of international standards. The purchaser of lights, ranging from bedside lamps to operating theatre units, is responsible for ensuring that a hospital's luminaires comply with relevant legislation. James Verrinder reports. PMID- 17724951 TI - Proper training key to defeating Legionella. AB - The long-awaited report from the Health & Safety Executive (HSE) into the Barrow Legionella outbreak has now been published and is in the public domain. Its conclusions and recommendations clearly recognise that the outbreak cannot, and should not, be attributed purely to one group or to the individuals working within one department. Moreover, the failings which contributed to the outbreak stretched from the lowest levels to the top of the council organisation. Develop Training's Tony Green explains how correct training can prevent future outbreaks. PMID- 17724952 TI - Concern remains over violence. AB - In the annual NHS staff survey run by the Healthcare Commission, personnel report that they are less stressed, suffer fewer work-related injuries and see fewer potentially harmful errors, but the results also highlight the levels of violence and abuse that they endure. PMID- 17724953 TI - MPs voice concerns over IT progress. AB - A report by the House of Commons Committee of Public Accounts has highlighted anxieties about the way in which information technology provision for the NHS is progressing. Health Estate Journal reports. PMID- 17724954 TI - Foundation Trusts require excellence. AB - As an increasing number of Trusts secure Foundation status, the importance of achieving excellence in estate management is further heightened. Report by Thomas Howard, a commercial property expert and member of the health team at law firm Browne Jacobson. PMID- 17724955 TI - Power increase at first ProCure21 project. AB - Throughout the UK, hospitals are embarking on new-build programmes to meet the needs of growing communities. However, site acreage and accommodation are often already under pressure, as Dale Power Solutions found when it was commissioned to increase standby power availability at the Friarage Hospital in Northallerton, North Yorkshire. PMID- 17724956 TI - New prion inactivation treatment presented. AB - Information on breakthroughs in prion decontamination and detection were presented by Dr Graham Jackson, head of molecular diagnostics at the Medical Research Council, to a Central Sterilising Club meeting held in Manchester earlier this year. PMID- 17724957 TI - Championing NHS design cause. AB - In support of NHS governance arrangements for assuring design quality and improving the patient environment, the Department of Health has recommended that all Trusts and PCTs embarking on new developments, whether they are refurbishment or new build projects, should appoint a Design Champion to their board of directors. Health Estate Journal reports. PMID- 17724958 TI - Game aims to prevent MRSA spread. AB - As the fight continues to limit the spread of MRSA infections in hospitals, Health Estate Journal examines how one games-based learning organisation has produced a novel way of assisting. PMID- 17724959 TI - [Diagnosis and treatment of tics]. AB - Tics are repetitive and sudden purposeless movements. Phenomenologically tics are differentiated as simple or complex, motor or vocal. Transient forms, which last less than 1 year, occur frequently in child hood. For Tourette syndrome, multiple simple and complex motor and vocal tics are present for more than one year. Frequently, additional symptoms of an obsessive-compulsive disorder or an attention deficit hyperactivity disorder are present. There is no therapy for the cause of tics. For minor symptoms or if a transient tic disorder is suspected, the use of medications should be avoided. Instead the patient and if necessary, the parents should be informed in detail and given advice. Particularly for children, it is important to exclude antiepileptic drugs as the cause of tics. For chronic tics and for pronounced symptoms, drug therapy with neuroleptic drugs or clonidine is a possibility. However, the efficacy of these substances is limited. PMID- 17724960 TI - [Attention deficit hyperactivity disorders in children and adolescents: diagnostic and therapeutic guidelines]. AB - The treatment of attention deficit hyperactivity disorders (ADHD) requires extensive diagnosis. Check lists and questionnaires may be helpful. Comorbidities are common and must be clarified. ADHD should be treated over a longer period of time. A multimodal treatment concept is recommended in which the administration of psychostimulants is combined with educational and behavioural therapeutic measures. PMID- 17724961 TI - [When should you suspect meningitis?]. AB - Bacterial meningitis is a life-threatening disease with a high mortality if left untreated. School-age children, adolescents and adults often present with typical symptoms such as fever, headache, neck stiffness and altered mental status, whereas infants show rather unspecific symptoms.The important task of the primary physician is to recognize the life-threatening condition in time and to refer the patient immediately to the next hospital. PMID- 17724962 TI - [Basic diagnostics of sleep disorders: possibilities of the family physician]. AB - Many sleep disorders can be definitively diagnosed using basic diagnostics in the family practice. Important elements of the diagnosis are the patient's general medical history and acquiring a description of the current phenomenology of the disorder. The use of sleep diaries and information provided by a third party are also helpful. For chronic sleep disorders, patient habits that are not in line with the rules of good sleep hygiene should be regarded as potential perpetuating causes of the disorder. In some cases, simple test procedures can also be useful. The identification or the exclusion of a primary physical or mental disease whose symptom may be the sleep disorder (example: insomnia for underlying depression) is important. In some cases, referral to a specialist or to a sleep medicine centre is necessary. PMID- 17724964 TI - [Early diagnosis of depression by the family physician]. AB - For patients with a depressive disorder, the family physician is often the first contact person. The doctor's early diagnosis and rapid initiation of treatment are hence of crucial importance. Because patients usually present with physical symptoms, the physician must actively explore the possibility of a depression; this means that the doctor must specifically ask about the principle symptoms and also explicitly address the subject of suicidal tendencies. The clarification of the course of depression (monophasic, recurrent or bipolar) and the exclusion physical causes are additional elements of the diagnosis. A screening is helpful for making a diagnosis, but does not replace a clinical examination. PMID- 17724963 TI - [Diabetic neuropathy: therapeutic nihilism is no longer acceptable]. AB - The repeatedly expressed doubts about the value of an effective therapy for diabetic neuropathies are no longer acceptable. Today a number of excellent longitudinal and cross-sectional studies, i.e. DCCT, Steno 2, DCCT/EDIC, European Diabetes Prospective Complications Study, are available. The attending physician should make every effort to diagnose diabetic neuropathies as soon as possible with all their multivarious manifestations. Treatment must be promptly, aggressively and multifactorially as described in evidence-based guidelines. In principle, the same risk factors apply to neuropathy in type 1 and type 2 diabetes as for macro-angiopathy and microangiopathy. Therapy focuses on establishing near-normal diabetes and blood pressure control, lipid management, intensive patient education, avoidance of exogenous noxae such as alcohol and nicotine and if necessary, an effective therapy of neuropathic pain. The objective of all diagnostic and preventive efforts must be always to avoid the development of the diabetic neuropathic foot syndrome, which is the most important end stage of somatic and autonomic diabetic neuropathy. PMID- 17724965 TI - [Antidepressants in the hands of the family doctor]. AB - Depression is today one of the widespread diseases that are first treated by the family doctor. In addition to empathetic and supportive talks with the patient and the positive reinforcement of an active behaviour pattern, basic psychotherapeutic treatment of depression also focuses on the prescription of an appropriate antidepressant. The pharmaceutical preparation, which is selected on the basis of its activity profile and tolerability, must be taken for a sufficient length of time and at an adequate dosage. PMID- 17724966 TI - [When the legs have to keep moving at night--the restless legs syndrome]. AB - The restless legs syndrome (RLS) is a frequently occurring neurological disease that is often associated with sleep disorders and reduced quality of life. The cause of RLS still has not been clearly established; however, the dopaminergic and opioid systems and iron metabolism appear to have major roles in the disease. The therapy of choice is treatment with dopaminergic drugs. In addition, opiates and anticonvulsants such as gabapentin are used. The most important side effect of dopaminergic therapy is augmentation. If therapy-related augmentation occurs while taking levodopa, the medication should be changed to dopamine agonists. If augmentation occurs while taking dopamine agonists, opiates or gabapentin should be taken instead. PMID- 17724968 TI - [Advances in the treatment of multiple sclerosis?]. AB - The natural course of multiple sclerosis (MS) is probably more favourable than previously assumed years ago. Since the introduction of interferons in Germany, the establishment and further development of new diagnostic criteria (McDonald criteria), the causal and symptomatic treatment possibilities and initiation of therapy early in the course of the disease have led to a considerable change in the treatment of MS. MS attacks are usually treated with the intravenous administration of high-dosed steroids. When the attack symptoms do not sufficiently subside, plasmapheresis can be considered. For long-term treatment of MS, beta interferon, glatirameracetate and natalizumab are available as basic causal therapy and natalizumab and mitoxantrone are available for escalation therapy. Frequently occurring spasticity, chronic fatigue syndrome, depression, cognitive disturbances, incontinence, pain, ataxia and sexual disorders must be treated symptomatically. Overall, the outpatient treatment of MS is complex and should be carried out with close cooperation between the family doctor, neurological practices and outpatient departments specialized in treating MS. PMID- 17724967 TI - [What should be done after the first TIA?]. AB - Transient ischaemic attacks (TIA) are neurological events caused by temporary cerebrovascular disorders whose effects can be fully reversed within 24 hours. TIAs are forewarnings of an impending stroke. On the average, 15% of the patients suffer a stroke within 90 days after a TIA; half of the strokes occur within the first 48 hours. This necessitates very prompt diagnosis that includes medical examination, determination of risk factors, ultrasound examination of the cerebral vessels, cerebral imaging, ECG and echocardiography. Secondary prevention includes administering platelet inhibitors or, in case of cardiogenic embolism, oral anticoagulants, treatment of vascular risk factors and a change in lifestyle. Surgical or interventional therapy is indicated if severe stenosis of the cerebral arteries is present. PMID- 17724969 TI - [Bipolar disorders: the disease of extreme emotions]. AB - Bipolar disorder is characterized by alternating phases of manic and depressive states that are separated by variably long and sometimes symptom-free intervals. Rapid changes in symptoms and mixed states during acute episodes can make diagnosis difficult. The risk of suicide is high. For diagnostic confirmation, the patient should be referred to a specialist as early as possible. The therapy should also be carried out in close collaboration with a neurologist or psychiatrist. The role of the family physician is to monitor the pharmaceutical phase prophylaxis and to attend to the patient's comorbidities. PMID- 17724970 TI - [Acute headaches--when to treat immediately, when to wait]. AB - Headaches are among the most frequently named symptoms in general practices. About 90% of the patients suffer from idiopathic headaches, for example, migraine or tension headaches, which are treated according to guidelines. An acute headache can however also be a symptom of a serious primary disease, such as subarachnoidal haemorrhage, arterial dissection, cerebral infarction, cerebral venous thrombosis or acute glaucoma. Patients with suspected symptomatic headaches must be immediately referred to a specialist or hospital for further diagnosis and therapy. PMID- 17724971 TI - [Botulinum toxin: a new dimension for spasticity]. AB - Today, botulinum toxin (Btx) belongs to the standard repertoire in the treatment of spasticity. It is usually used in combination with other measures, such as oral or intrathecal medicinal products or physiotherapy. Btx improves the ability to walk and stand of patients with spastic equinus deformity and hip and knee flexor spasticity. Btx treatment eases the care of patients with severe adductor spasticity and flexor spasticity of the extremities and hands and also the self care and dressing of patients with arm spasticity. Through the local application of Btx, painful spasms have become treatable without having to also accept the generally negative effects of, for example, oral antispasticity drugs. For children with congenital or who acquired spasticity in early childhood, the long term treatment with Btx can fundamentally contribute to the improvement of motor development. PMID- 17724972 TI - [Frequently occurring forms of dizziness and their treatment]. AB - Dizziness is not a unique clinical picture, but rather is the unspecific symptom of numerous diseases. Dizziness always develops when the real incoming vestibular, visual and somatosensory information contradict each other and the expected input signals. Disorders of the vestibular apparatus are the most frequent cause of dizziness; in contrast, cervicogenic causes play a secondary role. Dizziness syndromes usually have a favourable prognosis and can be successfully treated. PMID- 17724974 TI - [Update: migraine therapy 2007]. AB - Migraine therapy focuses on attack treatment for which analgesics, antiemetics and triptans are used. Triptans differ with regard to their effectiveness, tolerability, the speed with which the medication takes effect and duration of effect. Various pharmaceutical forms are available. Triptans are contraindicated for coronary, cerebral and peripheral vascular diseases and are also not suitable for emergency treatment. Primarily patients who have a high frequency of attacks or for whom triptans are contraindicated, not effective or not tolerated must rely on prophylactic migraine medications. Behavioural measures should accompany preventive medication. PMID- 17724973 TI - [Acetylcholinesterase inhibitors for dementia--an update]. AB - The efficacy of acetylcholinesterase (AChE) inhibitors for the treatment of dementia diseases has been established for both key cognitive symptoms and dementia-associated symptoms such as aggressiveness and the ability to perform activities of daily life. Presently three AChE inhibitors are approved for the treatment of mild to moderately severe Alzheimer dementia: donepezil, rivastigmine and galantamine. Rivastigmine is also approved for the treatment of Parkinson's dementia. The three substances differ in their efficacy and their pharmacological properties. AChE inhibitors should be used for long-term treatment. The clinical course should be monitored every six months. PMID- 17724975 TI - [Diagnosis and treatment of amyotrophic lateral sclerosis]. AB - Like Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which a very defined population of neurons selectively degenerates. Muscular atrophy and central paresis develop in ALS patients relatively quickly--usually within months to a few years. Bulbar symptoms such as swallowing disorders and dysarthria are frequently observed in the beginning. The disease progresses steadily and without remission. The average length of survival after diagnosis is two to three years. The diagnosis is made on the basis of a characteristic group of symptoms and confirmed or substantiated through additional clinical neurological tests. Currently, the cause of the disease cannot be treated. Treatment concentrates primarily on symptomatic measures and providing supportive devices. PMID- 17724976 TI - [Selective noradrenaline-dopamine reuptake inhibition (SNDRI). More latitude for antidepressive therapy]. PMID- 17724977 TI - [Differential diagnosis of somatoform disorders in elderly patients]. AB - The diagnosis of somatoform disorders in elderly patients is frequently difficult due to the presence of a mixture of symptoms related to organic pathological changes, medication side effects and mental processes. For this reason, important indications of somatoform disorders are difficulties in the doctor-patient relationship that result in the patient being convinced that he/she is suffering from an organic disease which the attending physician is not able to detect. In old age, numerous physical and social losses that must be coped with can be the source of emotional difficulties. While making a diagnosis, it is essential to recognize the underlying psychological connections to the physical symptoms of the patient. The goal is to gently and constructively expand the patient's organic explanation to include psychosomatic possibilities, for example within psychosomatic primary health care. To evaluate difficulties in a doctor-patient relationship, participation in Balint seminars can be very helpful. PMID- 17724979 TI - [Schizophrenic patients in the family practice]. AB - For over 50 years, therapy with antipsychotics represented the mainstay for the treatment of schizophrenia. While pharmacological antipsychotic approaches are especially important during the acute course of the disease, other therapeutic procedures such as psychotherapy and sociotherapy have become increasingly important for maintenance and relapse therapies. Treatment with newer atypical antipsychotics provides a pharmacological therapy that can be adapted to the needs of the individual patient and includes aspects such as favourable side effect profiles, better quality of life and hence, increased medication compliance. Negative symptoms still represent a therapeutic challenge, especially in conjunction with chronic residual symptoms. PMID- 17724978 TI - [Diagnosis and treatment of tremor in Parkinson's disease and essential tremor]. AB - For patients presenting predominantly or purely with tremor, the correct diagnosis of tremor-dominant Parkinson's disease (PD) versus essential tremor (ET) is very important for prognosis and effective therapy. ET tremor is usually characterized by symmetric bilateral postural and kinetic tremor, which may respond to low alcohol consumption. Many patients have a family history of ET tremors. Medical treatment with primidone or beta-blockers effectively controls ET tremor, but in many cases no treatment is needed at all. The typical tremor form of PD is an asymmetric rest tremor, which is treated with dopaminergic agents such as levodopa. Differential diagnosis of ET and PD may be difficult in a subset of PD patients who present with additional postural and kinetic tremor and in a minority of ET patients who show a clear asymmetry of their postural and kinetic tremor. In some patients with ET, the tremor can later become severe and even require treatment with deep brain stimulation. PMID- 17724980 TI - [Bonus-malus regulations in the framework of the AVWG guideline-suitable migraine therapy are possible]. PMID- 17724981 TI - Clinical snapshot. Feline leprosy. PMID- 17724982 TI - Piscine patients: basic diagnostics. AB - This article can serve as an introduction for practitioners who are interested in adding fish to their practice. It reviews the current literature, includes contributions from institutional collaborators, and draws on clinical expertise from diverse cases and applied research from the Animal Health Department at the New England Aquarium. Basic diagnostic approaches to piscine patients are featured. We hope to inspire other veterinary professionals to pursue diagnostics, perform surgery, and practice preventive medicine in aquatic animal patients. PMID- 17724983 TI - Mucosal immunity and chronic idiopathic enteropathies in dogs. AB - Gastrointestinal disorders, including chronic diarrhea, are common in canine general practice. Many of these diseases do not have a clearly defined underlying cause, despite thorough diagnostic investigation. This article reviews several syndromes with poorly understood causes that are associated with chronic diarrhea in dogs. Because the immune system plays a central role in the pathogenesis of many of these syndromes, gastrointestinal mucosal immunity is also reviewed. Therapeutic interventions discussed in this article, including diet, immunosuppressive agents, antibiotics, probiotics, and prebiotics, are mostly aimed at modulating the intestinal immune response. PMID- 17724984 TI - Husbandry considerations for better behavioral health in psittacine species. PMID- 17724985 TI - The cat conundrum. PMID- 17724986 TI - Clinical snapshot. Cuterebra fly Iarva. PMID- 17724987 TI - Clinical snapshot. Pneumothorax. PMID- 17724988 TI - Feline chronic renal failure: long-term medical management. AB - Chronic renal failure (CRF) is one of the most common illnesses of geriatric cats. Common clinical signs include polydipsia, polyuria, decreased appetite, weight loss, and vomiting. Although CRF is incurable, it may be possible to delay the progression of the disorder by feeding an appropriate diet and by monitoring and normalizing (if possible) several parameters, including blood pressure, serum phosphorus and potassium levels, parathyroid hormone levels, and proteinuria. PMID- 17724989 TI - Simple handling techniques for dogs. PMID- 17724990 TI - Hyperglycemia in critically ill patients. AB - Hyperglycemia is common in critically ill humans. Recent clinical trials have shown a significant reduction in morbidity and mortality rates with the use of intensive insulin therapy to maintain strict normoglycemia in critically ill patients. Hyperglycemia is associated with many detrimental effects, including reduced immune function, increased inflammation and coagulation, and modulation of the endothelium. Most of the evidence regarding the adverse effects of hyperglycemia is derived from humans with diabetes, cardiac failure, or traumatic brain injury. In addition to its anabolic effects on metabolism, insulin has antiinflammatory properties. To define the potential risks and benefits of intensive insulin therapy in critically ill animals, prospective, randomized clinical trials are necessary. PMID- 17724991 TI - Annual report of the National Influenza Surveillance Scheme, 2006. AB - Influenza surveillance in Australia is based on laboratory isolation of influenza viruses, sentinel general practitioner reports of influenza-like illness, and absenteeism data from a major national employer. In 2006, 3,130 cases of laboratory-confirmed influenza were reported to the National Notifiable Diseases Surveillance System, which was one-third lower than in 2005. The influenza season started in mid-June, with peak activity in late August. Influenza A was the predominant type notified (71%), however influenza B activity continued to increase as a proportion of reported cases. Reports of influenza-like illness from sentinel general practitioners showed a slow but steady increase throughout the first half of the year to peak in late August. In 2006, 657 influenza isolates from Australia were antigenically analysed: 402 were A(H3N2), 24 were A(H1N1) and 231 were influenza B viruses. Continued antigenic drift was seen with the A(H3N2) viruses from the previous reference strains (A/California/7/2004 and A/New York/55/2004) and drift was also noted in some of the A(H1N1) strains from the reference/ vaccine strain A/New Caledonia/20/99, although very few A(H1N1) viruses were isolated in Australia in 2006. The B viruses isolated were predominately of the B/Victoria-lineage and similar to the reference/vaccine strain B/Malaysia/2506/2004. PMID- 17724992 TI - Annual report of the Australian Gonococcal Surveillance Programme, 2006. AB - The Australian Gonococcal Surveillance Programme (AGSP) monitors the antibiotic susceptibility of Neisseria gonorrhoeae isolated in all states and territories. In 2006 the in vitro susceptibility of 3,850 isolates of gonococci from public and private sector sources was determined by standardised methods. Different antibiotic susceptibility patterns were again seen in the various jurisdictions and regions. Resistance to the penicillins nationally was at 34% and, with the exception of the Northern Territory, ranged between 17% and 51%. Quinolone resistance in gonococci increased, especially in Queensland, with resistance to this agent found in all jurisdictions. Nationally, 38% of all isolates were ciprofloxacin-resistant, and most of this resistance was at high minimum inhibitory concentration (MIC) levels. With the exception of the Northern Territory excepted, proportions of quinolone resistant gonococci ranged between 16% and 54%. All isolates remained sensitive to spectinomycin. Less than 1% of isolates showed some decreased susceptibility to ceftriaxone. A high proportion of gonococci examined in larger urban centres were from male patients and rectal and pharyngeal isolates were common. In other centres and in rural Australia the male to female ratio of cases was lower, and most isolates were from the genital tract. PMID- 17724993 TI - Annual report of the Australian Meningococcal Surveillance Programme, 2006. AB - In 2006 there were 271 laboratory-confirmed cases of invasive meningococcal disease analysed by the National Neisseria Network, a nationwide network of reference laboratories. The phenotypes (serogroup, serotype and serosubtype) and antibiotic susceptibility of 166 isolates of Neisseria meningitidis from invasive cases of meningococcal disease were determined and an additional 105 cases were confirmed by non-culture-based methods. Nationally, 217 (80%) confirmed cases were infected with serogroup B and 26 (9.6%) with serogroup C meningococci. The total number of confirmed cases was 74 (21%) fewer than the 345 cases identified in 2005. Numbers of cases decreased in all jurisdictions except Queensland. The age group showing the greatest decrease in numbers (by about one-third) was in those aged 25 years or more. A typical primary disease peak was observed in those aged 4 years or less with a lower secondary peak in adolescents and young adults. Serogroup B cases were 93% of all cases in those aged 4 years or less and 77% in those aged 15-24 years. The proportion of invasive disease represented by serogroup C disease was highest in the 20-24 years and 25-44 years age groups. The common phenotypes circulating in Australia were B:15:P1.7, B:4:P1.4, C:2a:P1.4 and C:2a:P1.5, but again with significant jurisdictional differences. No evidence of meningococcal capsular 'switching' was detected. About two thirds of all isolates showed decreased susceptibility to the penicillin group of antibiotics (MIC 0.06-0.5 mg/L). All isolates remained susceptible to rifampicin and ciprofloxacin. PMID- 17724995 TI - Compliance with three simultaneous vaccinations due at the one visit at 12 months of age in Australia. AB - The introduction of meningococcal C conjugate vaccine (Men C) into the National Immunisation Program Schedule in January 2003 was the first time that 3 simultaneous vaccine injections were recommended for all Australian children. This study aimed to assess the level of simultaneous vaccination at 12 months of age for 4 cohorts of Australian children. The percentage of children with all 3 vaccinations given simultaneously by jurisdiction increased for all states and territories across the 4 study cohorts, however some jurisdictions fared better than others. The percentage of children with all 3 vaccinations given simultaneously varied by the provider type of the Men C vaccine, being lower for general practitioner providers than other providers. Men C vaccine was the vaccine most commonly delayed. The percentage of children who received all 3 vaccinations simultaneously in Australia also varied by indigenous status, with Indigenous children more likely to receive immunisations simultaneously. The study suggests that some children in Australia are at risk of receiving Men C vaccine late, especially children in jurisdictions where general practitioners give the majority of vaccinations. PMID- 17724994 TI - Creutzfeldt-Jakob disease: Australian surveillance update to March 2007. AB - From October 1993, prospective, national surveillance of the rare class of neurodegenerative diseases known as transmissible spongiform encephalopathies (TSEs) has been performed by the Australian National Creutzfeldt-Jakob Disease Registry. Surveillance of TSEs prior to October 1993, involved the retrospective ascertainment of TSE cases from 1970 to 1993. In this report, surveillance data for 2006 are presented in detail and compared to cumulative national TSE ascertainment as well as international experience. The higher incidence of TSEs in 2006 is not without precedent and can be attributed to higher referrals and consequent post-mortem rates. PMID- 17724996 TI - Bordetella pertussis PCR positivity, following onset of illness in children under 5 years of age. AB - Bordetella pertussis is a significant cause of respiratory illness and an ongoing public health problem. Pertussis polymerase chain reaction (PCR) testing has been widely utilised since 2001, especially in infants. Uncertainty exists as to how long PCR remains positive following symptom onset. Further information on the time frame for pertussis PCR testing would assist diagnosis, epidemiological research and disease control. The Brisbane Southside Population Health Unit (BSPHU) conducted a retrospective analysis of enhanced surveillance data from pertussis notifications between January 2001 and December 2005, in children less than 5 years of age, in the BSPHU reporting area with the aim to determine the possible range of duration of Bordetella pertussis PCR, from symptom onset for this age group. Of 1,826 pertussis notifications to BSPHU between January 2001 and December 2005, 155 (8.5%) were children under 5 years of age, with 115 pertussis PCR positive results. Analysis indicated a range of PCR positivity from day one to day 31 from the onset of catarrhal symptoms with most (84%) being within 21 days from onset of catarrhal symptoms. The range of PCR positivity following onset of paroxysmal cough was from day one to day 38 with most (89%) being within 14 days from the onset of paroxysmal cough. This review of pertussis PCR data in young children showed that PCR positive results generally mirrored the understood length of infectivity with regard to both catarrhal symptoms and paroxysmal cough; namely that PCR positive results were obtained at least 21 days following onset of catarrhal symptoms and at least 14 days following onset of paroxysmal cough. PMID- 17724997 TI - Pertussis epidemiology in Australia over the decade 1995-2005--trends by region and age group. AB - Important changes have occurred in the National Immunisation Program for pertussis during the decade 1995-2005, including the introduction of acellular pertussis vaccine for all doses, removal from the schedule of the booster dose at 18 months, and the introduction of a booster dose for adolescents. In addition, the coverage of pertussis vaccine at 12 and 24 months has substantially increased as recorded by Australian Bureau of Statistics surveys and the Australian Childhood Immunisation Register. There were 75,458 notifications nationally between 1995 and 2005, with little change in the annual number of notifications at the national level but with periodic and dramatic changes in the age distribution of notified cases. Pertussis is well controlled in the 1-4 and 5-9 year age groups, and the highest annual notification rates continue to be in infants under 6 months of age. Adolescents aged 10-19 years had high notification rates in all states and territories, over this period, but 63% of notifications are now in the 20-59 year age range. Following the introduction of a fifth dose for adolescents, the current focus should be on protecting infants too young to be vaccinated and further defining the true morbidity of the disease in the elderly population. PMID- 17724998 TI - Epidemiology of Leptospira weilii serovar Topaz infections in Australia. AB - Leptospirosis is a zoonotic disease with a worldwide distribution. Leptospira weilii serovar (sv.) Topaz is a newly described serovar first isolated in the far north of Queensland, Australia. The epidemiology of L. weilii sv. Topaz infections in Australia was characterised through the use of surveillance questionnaires and molecular studies. There have been 24 human and 2 animal (bovine and bandicoot) L. weilii sv. Topaz infections diagnosed since 1991. The majority of these infections have occurred in Far North Queensland, with the remaining infections occurring in South East Queensland and in Western Australia. The majority of patients with L. weilii sv. Topaz infections presented with classical leptospirosis symptoms including; fever, headaches, sweats, chills and myalgia. The occupations of human cases of L. weilii sv. Topaz infection included banana farming, dairy and beef cattle production and tourist related activities. Fluorescent amplified fragment length polymorphism (FAFLP) was performed on 15 L. weilii sv. Topaz isolates including 2 animal isolates. Clustering analysis grouped the 15 isolates into 5 main clades with 13 unique FAFLP profiles. A high level of relatedness was demonstrated between 2 animal and 2 human isolates. PMID- 17724999 TI - Q fever cases in the Northern Territory of Australia from 1991 to 2006. AB - Q fever (infection with Coxiella burnetii) has been uncommon in Australia's Northern Territory, with no reported cases until 2002. Since then, twelve cases of Q fever have been reported, representing a much lower notification rate than in surrounding Australian states. Three cases were identified in Central Australia during 2006, prompting this review of clinical and epidemiological features of all notified Northern Territory cases. Three patients required Intensive Care admission, 1 died, 5 had moderately severe illness, 2 were treated as outpatients and 2 were excluded as unlikely Q fever cases on clinical grounds. Hospital stays were long (median length of stay 9.5 days), and diagnosis and definitive therapy were generally delayed. Although macrolides and quinolones have some reported efficacy against C. burnetii, 2 patients experienced prolonged fever (5 and 9 days respectively) despite azithromycin, and the fatality occurred in a patient treated with multiple antibiotics including ciprofloxacin. Four patients were Aboriginal, 3 were tested for HTLV-1 and 2 were positive. The patient who died was diabetic. None of acute and chronic manifestations of Q fever is required in the Northern Territory. Early institution of doxycyline in suspected cases is recommended, and more rapid diagnostic methods including polymerase chain reaction testing should be considered. Host risk factors for chronicity, which may be of particular importance in Indigenous patients, merit attention. Given the lack of occupational exposure in these cases, there seems little reason to change the current Northern Territory policy of opting out of the National Q Fever Vaccination Program. Recognised alternative exposures, such as non-occupational livestock and domestic animal contact, require consideration as local Q fever sources. PMID- 17725000 TI - Reduction in invasive meningococcal disease in Queensland: a success for immunisation. AB - Since 2003, the Australian government has funded a conjugate serogroup C meningococcal vaccine for those aged over 1 year and born since 1 January 1984. This summary of the epidemiology of invasive meningococcal disease (IMD) in Queensland assesses the effect that the vaccination program has had on IMD notifications. In Queensland, IMD cases are notified to the Notifiable Conditions System by clinicians and laboratories. Additional surveillance data are collected by population health units from relatives of the case, the case and medical practitioners. In 2005, Queensland recorded its lowest number of cases and lowest incidence of IMD since statewide surveillance began. This remained low in 2006. The serogroup C rate in Queensland also declined to its lowest in 2006. The pattern of age specific incidence remains similar, though rates are lower in all but those aged less than 12 months. However, Indigenous rates are still twice non Indigenous rates. The case fatality rate for IMD (all serogroups) has declined, possibly due to the reduced incidence of serogroup C and septicaemia cases. The program appears to have mostly achieved its aims of: reducing illness and death in the population at highest risk; inducing immunity in those who are vaccinated; and reducing the incidence of disease. However, there is considerable natural fluctuation in the rates of IMD and continued surveillance will be needed to monitor trends. PMID- 17725001 TI - Meningococcal septicaemia and a case of clinically mild illness. PMID- 17725002 TI - OzFoodNet quarterly report, 1 January to 31 March 2007. PMID- 17725003 TI - Communicable diseases surveillance. PMID- 17725004 TI - The Editors' responsibility. PMID- 17725005 TI - Obesity prevention programs demand high-quality evaluations. AB - Obesity prevention programs are at last underway or being planned in Australia and New Zealand. However, it is imperative that they are well-evaluated so that they can contribute to continuous program improvement and add much-needed evidence to the international literature on what works and does not work to prevent obesity. Three critical components of program evaluation are especially at risk when the funding comes from service delivery rather than research sources. These are: the need for comparison groups; the need for measured height and weight; and the need for sufficient process and context information. There is an important opportunity to build collaborative mechanisms across community-based obesity prevention sites to enhance the program and evaluation quality and to accelerate knowledge translation into practice and policy. PMID- 17725006 TI - A feasible method for linkage studies avoiding clerical review: linkage of the national HIV/AIDS surveillance databases with the National Death Index in Australia. AB - OBJECTIVE: To assess the sensitivity and specificity of linkage of HIV/AIDS diagnoses in Australia to the National Death Index (NDI). METHODS: An aggregated file containing 19,772 matched HIV/AIDS diagnoses reported to the national HIV/AIDS databases from 1980 to 30 June 2004 was linked to the NDI using probabilistic linkage methods based on the namecode, date of birth, and sex as identifiers. Based on the 6,900 HIV/AIDS known deaths reported by 1 January 2003 and 1,455 known non-deaths with an active follow-up beyond 1 January 2003, the different combinations of weights assigned to matched pairs were examined to obtain maximum sensitivity and specificity. RESULTS: The trade-off between sensitivity and specificity was used to obtain an optimal linkage. The optimal linkage was found to link 5,658 of the 6,900 HIV/AIDS known deaths (a sensitivity of 82%), and 116 false positives of the 1,455 known not deaths (specificity of 92%). Causes of deaths were recorded for 86.5% of deaths that were linked to the NDI. CONCLUSION: This is a feasible method for conducting linkage studies if both the identifying deaths and non-deaths are available. The relatively poor sensitivity could be due to limited identifiers available for linkage on the HIV/AIDS databases. PMID- 17725007 TI - Community attitudes to the collection and use of identifiable data for health research--is it an invasion of privacy? AB - OBJECTIVES: To investigate community views on the statutory collection of identifiable data by the Western Australian Birth Defects Registry and the extent to which the use of such data is perceived to be an invasion of privacy, when balanced against the community benefit of three public health scenarios. METHODS: Cross-sectional, computer-assisted telephone interviewing survey. Six hundred respondents were recruited randomly from the electronic version of the Western Australian telephone directory. RESULTS: Interviews were conducted in August 2006 and the response rate was 78%. Most respondents indicated support for statutory notification of cases (79%) and did not consider the statutory notification of postcodes (85%) and names and addresses (65%) to be an invasion of privacy. Similarly, most (76%) did not consider the receipt of a letter requesting participation in research to be an invasion of privacy. Overall, 55% considered none of these to be an invasion of privacy and only 4% considered all to be an invasion of privacy. CONCLUSIONS: Most Western Australians do not consider the statutory inclusion and use of identifiable data by the WA Birth Defects Registry to be an invasion of privacy, to the extent that such data are required for legitimate public health research, would be notified by the registrant's medical practitioner and would be kept confidentially and securely. PMID- 17725008 TI - A pilot study investigating of the nature of point-of-sale alcohol promotions in bottle shops in a large Australian regional city. AB - OBJECTIVE: The promotion of alcohol by retailers and media can contribute to a culture of excessive alcohol consumption, but the effect of non-advertising alcohol promotions has largely been neglected. This study sought to gather initial data on this important area. METHOD: An observational study of alcohol point-of-sale promotions in the Wollongong CBD area, conducted in July-August 2005. RESULTS: We identified 17 different promotions in three categories: gift with purchase; competitions; and buy some, get some free. CONCLUSION: Given previous research demonstrating the relationship between increased alcohol consumption and both ownership of alcohol-related merchandise and reduced per unit price, it appears that point-of-sale promotions may have the potential to further increase alcohol consumption among young people. IMPLICATIONS: Only when the extent and impact of such promotions is demonstrated will we be in a position to effectively advocate for appropriate regulations to ensure young people are not exposed to marketing strategies that further increase their exposure to alcohol-related harms. PMID- 17725009 TI - It's enough to make you sick: the impact of racism on the health of Aboriginal Australians. AB - BACKGROUND: Experience of interpersonal racism has been neglected as a mechanism by which inequalities between Aboriginal and non-Aboriginal people are created and maintained. METHODS: Cross-sectional survey of randomly selected residents of a rural Australian town (n=639). Interpersonal racism was measured by two questions on experiences in the past four weeks of negative racially based treatment that evoked an emotional or physical response. Health was measured with the mental and physical health component scores of the Short-Form 12 and self reported fair or poor general health. Linear and logistic regressions modelled the effects of interpersonal racism on health, controlling for age, sex, socio economic status and Aboriginality. FINDINGS: The 183 Aboriginal respondents had lower health component scores, were more than twice as likely to report fair-to poor general health (34% compared with 17%, p<0.001), and 2.6 to 5.0 times more likely to report negative racially based treatment. Demographic and socio economic characteristics were not associated with reporting negative racially based treatment. After controlling for other variables, Aboriginal respondents who reported negative treatment were more likely to have poor health on all three measures. Non-Aboriginal respondents who reported experiencing negative treatment had lower mental health component scores. IMPLICATIONS: Experiencing racist treatment should be recognised as a social determinant of health. Improved health care and other initiatives may not eliminate health inequalities in the absence of fundamental changes in how non-Aboriginal people behave towards Aboriginal people. PMID- 17725010 TI - "The dust hasn't settled yet": the National Q fever Management Program, missed opportunities for vaccination and community exposures. AB - AIMS: To determine the proportion of notifiable cases of Q fever attributable to occupational and community exposures and to identify missed opportunities for Q fever vaccination in notifications of occupational exposures. METHODS: A review of Q fever notifications to the BSPHU from January 2000 to September 2006 was undertaken. Notifications were categorised according to probable exposure source. Occupational exposures were further categorised according to reported past exposure to Q fever and Q fever vaccination status. RESULTS: One hundred and ninety-one Q fever notifications were identified, with occupational exposure reported in 106 cases and community exposure reported in 69 cases. In the occupational exposures, 76 cases (71%) were not vaccinated, 15 (14%) reported past exposure to Q fever and eight reported vaccination prior to illness onset, but vaccination status could not be independently verified. Community acquired Q fever was most commonly attributed to living or working near a high-risk industry (26, 38%), incidental exposures such as farm visits, or attending sale yards (27, 39%). CONCLUSIONS: Occupationally acquired cases of Q fever continue to be reported in significant numbers and opportunities for vaccination are being missed. There is an ongoing need to ensure that all employees in high-risk industries are screened and vaccinated. The proportion of community acquired notifications of Q fever has increased since the National Q fever Management Program started, commensurate with the decline in occupationally acquired cases. These proportions may be expected to change with the cessation of the program in Queensland in December 2006. PMID- 17725011 TI - Health services utilisation and barriers for settlers from the Horn of Africa. AB - OBJECTIVE: To examine health services use and barriers for recently arrived immigrants from the Horn of Africa. METHOD: A cross-sectional study conducted in Melbourne, Australia, with a convenience sample of newly arrived immigrants (n=126) from Somalia (n=67), Ethiopia (n=24), Eritrea (n=26) and Sudan (n=6). RESULTS: GPs were the major health providers for participants, yet 22 (17%) respondents had not yet accessed health services in Australia. Thirty-three (26%) participants reported having had an unmet health concern for which they would have liked to seek advice. The most commonly identified barriers to health care and recommendations for improving services were associated with communication. CONCLUSIONS: This study illustrates unmet health needs among new arrivals and a need for linguistically appropriate information about the use of Australia's health system. IMPLICATIONS: The findings support increased use of professional interpreting services and support for new arrivals in making initial contact with the health system. PMID- 17725012 TI - Socio-economic differences in public opinion regarding water fluoridation in Queensland. AB - OBJECTIVE: To describe public opinion relating to the fluoridation of drinking water in a sample of the Queensland population. METHOD: Data were collected by means of a computer-assisted telephone interview survey from a sample of the Queensland population. Descriptive statistics and logistical regression were used to examine associations between variables. RESULTS: Seventy per cent of the total sample supported water fluoridation of their local supply. More than 71% of the total sample agreed that water fluoridation was safe. People living in areas of higher socio-economic/relative socio-economic advantage were more likely to support the addition of fluoride to local drinking water and agree that it was safe. Opinions about fluoridation varied by respondent age and gender. CONCLUSIONS: General support was found in this sample of the Queensland population for fluoridation of drinking water. IMPLICATIONS: In Queensland, fluoridation of the water supply is now a political decision. Information about public opinion on fluoridation may assist decision makers in the final determination. PMID- 17725013 TI - The effects of different regulation systems on television food advertising to children. AB - OBJECTIVE: The aim of this study was to model children's potential exposure to television food advertisements under different regulatory scenarios to demonstrate the policy implications of regulatory change in Australia. METHODS: Television advertising data was collected from Sydney commercial television channels from 14-20 May 2006. Extrapolating from these data, the patterns of food advertising under four regulatory scenarios were examined, including arrangements restricting the content, volume and timing of advertisements. RESULTS: Each scenario resulted in a reduction of total and non-core food advertisements. The scenario to restrict non-core food advertisements during the major viewing period (7:00-20:30) led to the largest reduction in total and non-core food advertisements (79.2% reduction), with no change in the frequency of core food advertisements. CONCLUSIONS: The results illustrate the potential for reducing children's exposure to food advertising through simple regulatory restrictions. IMPLICATIONS: This research contributes to future debates on the regulation of television food advertising. It is particularly relevant as Australian regulations will be under review in 2007. PMID- 17725014 TI - Tobacco consumption in New Zealand: why did it fall? AB - OBJECTIVE: To estimate the relative contributions of trends in smoking prevalence and trends in smoking intensity (average number of cigarettes smoked per day) to the observed decline in per capita tobacco consumption in New Zealand from 1984 to 2004. METHOD: Tobacco consumption and smoking prevalence time series data were sourced from Statistics New Zealand and the ACNielsen Omnibus Survey respectively and checked for accuracy against other sources. The contribution of changes in smoking prevalence to the observed decline in tobacco consumption was estimated by counterfactual modelling. The corresponding contribution of trends in smoking intensity was then calculated by difference. RESULTS: Changes in smoking prevalence accounted for 48% of the decline in per capita tobacco consumption from 1984-89 and for 39% thereafter. Correspondingly, changes in smoking intensity accounted for 52% of the consumption decline during the first five years of the study period and 61% thereafter (i.e. from 1990 to 2004). DISCUSSION: Understanding the relative contributions of trends in smoking prevalence and smoking intensity to the observed decline in per capita tobacco consumption is important, because the relationship between smoking intensity and health effects is non-linear. Our results indicate that the dramatic fall in tobacco consumption in New Zealand over the past 30 years will not be accompanied by an equivalent reduction in tobacco-attributable morbidity and mortality. Furthermore, our findings raise doubts as to how much longer tobacco consumption will continue to decline, given that smoking intensity is already low. The key message for the tobacco control program is to re-focus on helping smokers to quit and stay quit. PMID- 17725015 TI - Pharmaceutical brand substitution in Australia--are there multiple switches per prescription? AB - BACKGROUND: In Australia, brand substitution by pharmacists has been possible since 1994. There is no limit to the number of substitutions per prescription. Doctors have expressed concern that patients may receive a different product each time their prescription repeats are dispensed, which has the potential to confuse patients. It is unknown how often multiple substitutions per prescription occur. OBJECTIVES: We aimed to identify the number of switches per prescription for a range of medicines and to determine the number of different brand and generic products supplied on each prescription. METHODS: Repatriation Pharmaceutical Benefits Scheme prescription claims between 1 January 2001 and 28 February 2006 were identified for atenolol, citalopram, enalapril, metformin, omeprazole, ramipril, and simvastatin. Original prescriptions with five repeats and all supplies dispensed were included. Switches were identified if a different product was supplied on consecutive repeat dispensings. RESULTS: 533,279 original prescriptions were included. 488,735 (92%) had no switches on repeats and 37,513 (7%) had only one switch. Only 1% of all prescriptions had more than one switch identified on repeats, and in most cases only two different products were supplied. None of the prescriptions had a different product supplied on each dispensing. CONCLUSION AND IMPLICATIONS: Multiple switches per prescription are uncommon and multiple different products are rarely supplied on repeats of the same prescription. The rules of the brand substitution policy appear to be adequate in allowing brand choice for patients, without leading to multiple switches per prescription. PMID- 17725016 TI - "It's much easier than going to the dentist": high levels of satisfaction in a mammography screening program. AB - OBJECTIVES: To develop a suitable instrument for measuring client satisfaction in the BreastScreen New South Wales (NSW) program and to use the instrument to measure client satisfaction. METHOD: The survey was designed and administered to 2,091 women who attended mammography screening in the BreastScreen NSW program during 2001 (85% response rate). The survey evaluated experiences of making appointments, the screening environment, the screening procedure, and the receipt of results. Socio-demographic differentials in client satisfaction were examined using logistic regression models. RESULTS: The majority of women were highly satisfied with their experience, with transport/parking, breast discomfort and time to results causing the most dissatisfaction (8-9%). The main source of dissatisfaction was during the appointment and related to discomfort during the mammogram (9%) and breast problems following the mammogram (9%). Predictors of dissatisfaction with screening (p<0.05) included high education level (OR=1.4), non-Australian born (OR=1.4), and aged 40-49 years (OR=1.6). CONCLUSIONS: Although overall satisfaction was high, the survey indicated service functions where improvements could be made. IMPLICATIONS: This research has developed an appropriate tool for assessing and monitoring client satisfaction with breast screening services. PMID- 17725017 TI - Development of a healthy food basket for Victoria. AB - OBJECTIVE: Access to an affordable, nutritious food supply is an important determinant of population health. Healthy food basket surveys have been used across Australia as a tool to monitor food cost, quality and variety. The release of the revised Nutrient Reference Values, together with local interest in food security, highlighted the need to develop a Victorian Healthy Food Basket to reflect the food access issues of the Victorian population. METHOD: The development took place at Monash University, Victoria, in December 2006. Demographic and food purchasing data were used to define the family types and foods in the healthy basket, respectively. The revised Nutrient Reference Values were used to benchmark the nutritional adequacy of the basket. RESULTS: A Victorian Healthy Food Basket consisting of 44 core and non-core foods was developed. The quantities of the 44 items in the basket were modified to meet the nutritional needs of four different family types most common in Victoria and those most vulnerable to food insecurity: two adults and two children; a single mother and two children; a single adult male; and a single elderly female. CONCLUSION: Victoria has a local tool to monitor healthy food cost and accessibility that meets at least 85% of all individual nutrient requirements and at least 95% of all energy requirements for four family types for a fortnight. IMPLICATIONS: The Victorian Healthy Food Basket provides an additional tool to monitor the cost and access to healthy food in Victoria. PMID- 17725018 TI - It's time to determine the cost of a healthy diet in Australia. PMID- 17725019 TI - Aboriginal and non-Aboriginal health differentials in Australian prisoners. AB - OBJECTIVE: Compare the self-reported physical and mental health of Aboriginal and non-Aboriginal prisoners in New South Wales (NSW). DESIGN: Cross-sectional random sample. SETTING: Twenty-nine correctional centres (27 male and two female) in NSW. PARTICIPANTS: 747 men (227 Aboriginal) and 167 women (29 Aboriginal) in full time custody. METHODS: Face to-face interviews were used to record self-reported health status. RESULTS: Aboriginal prisoners differed significantly from non Aboriginal inmates in several socio-demographic and criminographic factors. However, few differences were observed in health status between Aboriginal and non-Aboriginal men and women. After adjusting for age, Aboriginal men were more likely to report high blood pressure and diabetes. No differences were found in chronic health conditions in the female group. Aboriginal men had higher SF-36 scores than non-Aboriginal men on general health, vitality, and mental health. Aboriginal women had lower scores than non-Aboriginal women on social functioning and role-emotional but scored higher on the role-physical dimension. Aboriginal inmates were more likely to report seeing certain health professionals (doctors, dentists, drug and alcohol counsellors, and optometrists) in prison compared with the community. CONCLUSIONS: The health of Aboriginal and non-Aboriginal prisoners is remarkably similar in this population group. Few differences were observed in self-reported chronic health conditions. Aboriginal prisoners report using prison health services more while in prison compared with the community. This highlights that for many, prison is a rare opportunity to contact health services. PMID- 17725020 TI - Developing a collaborative research system for Aboriginal health. AB - OBJECTIVE: Investigator-driven research and the use of peer review are contentious in community-based research and are particularly problematic in Indigenous research. In this project, we conducted a qualitative study among stakeholders in an Australian Aboriginal majority-controlled research-funding organisation to examine the research funding process. METHODS: A steering group guided the project and contributed to the research findings. In-depth interviews (n=18) with stakeholders in the Cooperative Research Centre for Aboriginal Health were conducted to canvass views on the research funding process and options for alternate processes. A discussion document, supported by an extensive literature review, was provided prior to interview. This research was an iterative process where the discussion document and interview schedule were revised as the research findings informed the project. FINDINGS: Participants overwhelmingly endorsed a move to a more collaborative research culture, although the form the culture might take varied. Suggested elements included involvement of grant funding bodies as brokers in building collaborative networks and the substitution of named 'critical friends' for blinded peer review. Barriers to changing the research culture to a more collaborative model were described. CONCLUSIONS AND IMPLICATIONS: A collaborative structure with targeted project development would permit redistribution of the time and effort (previously expended on peer review) into research development and would increase community participation in decision making in the research funding process. PMID- 17725021 TI - Benzodiazepine prescribing in elderly Australian general practice patients. AB - OBJECTIVE: The use of benzodiazepines by elderly people is of limited therapeutic benefit and increases the risk of adverse events. This study aimed to examine the extent to which benzodiazepines are prescribed for elderly Australians. METHODS: Data for 3,970 individuals aged 65 years or more were extracted from a general practice database. Benzodiazepine prescriptions for 2002 were reviewed. RESULTS: Overall, 16% (95% CI 11-21%) of elderly patients had at least one benzodiazepine prescription. Females were almost twice as likely as males to be prescribed a benzodiazepine and prescription prevalence increased with age. CONCLUSIONS: Despite risks, benzodiazepines are widely prescribed for the elderly. Limited availability and cost of alternative therapies and pressures on the primary care system in Australia may contribute to their continued overuse. IMPLICATIONS: The prescribing of benzodiazepines for elderly Australians needs to be reduced by better managing sleep and anxiety problems. PMID- 17725022 TI - Too small for concern? Public health and nanotechnology. AB - While advances in nanotechnology promise to deliver significant benefits to many aspects of health care, there is increasing concern that regulatory regimes do not adequately capture the potential risks associated with this new technology. Concerns have arisen due to preliminary evidence suggesting that some engineered nanoparticles may display undesirable toxicological properties, presenting potential risks to human and environmental health and safety. Within this context, the role of Australia's National Industrial Chemicals and Assessment Scheme and the Therapeutic Goods Administration in regulating nano-based substances is explored. Drawing on earlier regulatory failures, combined with the scientific uncertainty surrounding nanotechnology, this article recommends that Australia adopt a proactive regulatory approach to nanotechnology through amendments to present legislative regimes. The approach articulated in this article strikes a balance between the current approach and that of the European Union's comprehensive new chemicals regime. Immediate regulatory change is called for in order to ensure that the health of the Australian public is adequately protected over the coming years. PMID- 17725023 TI - The solarium industry--how many operators are there in Australia? PMID- 17725024 TI - Smoking and surgery: an opportunity for health improvement. PMID- 17725025 TI - Gardasil and mass psychogenic illness. PMID- 17725026 TI - [Comparative analysis of sensitivity of cholinesterases of various origin to monoonium reversible inhibitors]. AB - Analytical review of literature data has been presented about constants of interaction of cholinesterases of various animals (verterbrates and squids) with 89 onium (ammonium, phosphonium, and sulfonium) reversible inhibitors forming homologous series with regularly changed structure. Values of competitive, uncompetitive, and generalized inhibition constants have been compared. On this basis, conclusions are made about mechanism of action of the studied compounds and the predominant areas of their sorption--in the <> or peripheral <> sites of the enzymes. The presented data are discussed from the point of view of comparative biochemistry and in the light of the current information about structure of the cholinesterase active center. PMID- 17725027 TI - [Adenosine triphosphatases of cestodes Bothriocephalus scorpii]. AB - Activities and properties of adenosine triphosphatases (ATPases) have been studied in mitochondrial and microsomal fractions of cestodes Bothriocephalus scorpii parasitizing in pyloric appendages of the Brandt's bullhead Myoxocephalus brandti. The highest activity has been revealed in the mitochondrial fraction. The mitochondrial and microsomal fractions of B. scorpii have the ATPase activity dependent on the presence of cations Mg2+, Mn2+, and Ca2+. Effects of ions and inhibitors on the B. scorpii ATPase activity with various cations have been studied. Both subcellular fractions are able to hydrolyze, apart from ATP, also GTP, CTP, and UTP. PMID- 17725029 TI - [Biochemical parameters of blood plasma of the harp seal Pagophilus groenlandicus Erxleben, 1777 (Pinnipedia, Procidae) of various ages]. AB - Results of study of several blood biochemical parameters of the harp seal Pagophilus groenlandicus Erxleben, 1777, from birth to the adult state are presented. The following age groups of the animals have been studied--newborns, 1.5-2 months, 1 year, 2 years, 3 years, and adults (older than 6 months). The content of total protein and its fractions, free amine nitrogen, urea, creatinine, glucose, total lipids, total calcium, and inorganic phosphorus was determined in the seal blood plasma. Differences of the degree of expression of levels of all studied parameters in the course of early postnatal ontogenesis of the animals have been established. The most significant metabolic changes in the harp seals were revealed at the period of end of weaning and transition to independent ingestion and then after the first year of life. PMID- 17725028 TI - [Comparative properties of sensitive to GABAA-ergic ligands, Cl(-), HCO3(-) activated Mg2+-ATPase from brain plasma membranes of fish and rats]. AB - Action of Cl(-) + HCO3(-) ions on Mg2+-ATPase from brain plasma membranes of fish and rats has been studied. Maximal effect of the anions on the <> Mg2+ ATPase activity is revealed in the presence of 10 mM Cl(-) and 3 mM HCO3(-) at physiological values of pH of incubation medium. The studied Cl(-), HCO3(-) activated Mg2+-ATPases of both animal species, by their sensitivity to SH reagents (5,5-dithiobis-nitrobenzoic acid, N-ethylmaleimide), oligomycin, and orthovanadate, are similar to transport ATPase of the P-type, but differ from them by molecular properties and by sensitivity to ligands of GABAA-receptors. It has been established that the sensitive to GABAA-ergic ligands, Cl(-), HCO3(-) activated Mg2+-ATPase from brain of the both animal species is protein of molecular mass around 300 kDa and of Stocks' radius 5.4 nm. In fish the enzyme is composed of one major unit of molecular mass approximately 56 kDa, while in rats- of three subunits of molecular masses about 57, 53, and 45 kDa. A functional and structural coupling of the ATP-hydrolyzing areas of the studied enzyme to sites of binding of GABAA-receptor ligands is suggested. PMID- 17725030 TI - [Biochemical strategy of survival of the freshwater mollusc Lymnaea stagnalis at near-zero temperatures]. AB - Effect of an autumn-winter decrease of the environmental temperature on changes of the content of free amino acids and reducing sugars was studied in tissue fluids of the freshwater mollusc L. stagnalis. At a decrease of the temperature to 4 and 0 degrees C at the autumn period, concentration of free alanine rose several times; an increase of histidine, glutamate, glycine, and serine concentrations was less pronounced. Accumulation of methionine, leucine, isoleucine, tyrosine, and phenylalanine was revealed at 0 degree C. In the state of long hypobiosis (at 4 degrees C), pools of all amino acids fell 4-8 times; essential amino acids, except for lysine, were not detected at all. Both at the summer and at the autumn periods, high concentrations of free fructose and glucose were revealed. In the process of hypobiosis the fructose pool decreased almost 35, while the glucose pool--12 times. Maltose that was absent in summer was found at 4 and 0 degree C as well as after 2.5 months of hypobiosis. The changes of the studied parameters in L. stagnalis in response to hypothermia are compared with the corresponding parameters of changes in cryoresistant animals in response to negative temperatures. PMID- 17725031 TI - [Aminergical regulation of pheromone sensillae in the cockroach Periplaneta americana]. AB - Vast adaptability of insects is provided substantially by fast tining of physiological functioning of an organism to conform to the permanently changing environmental conditions. One of the mechanisms of plasticity in insects is modulation of performance of their sense organs by neurohormones. Activity of at least three out of four receptor cells located in cockroach pheromonesensitive sensilla is under influence of octopamine. Increase in firing rate of pheromone receptor cells and decrease in electroantennogram amplitude is accompanied by enhanced behavioural responses of male cockroaches to sex pheromone. The effect of octopamine on reception of a repellent (1,8-cineole) by an insect is reported for the first time. Simultaneous modulation of responses of receptor cells located in sex specific sensilla to semantically different odorants implies their cooperation in formation of insect's behaviour. PMID- 17725032 TI - [Effect of temperature on auditory receptor functions in bushcrickets (Orthoptera, Tettigonioidea)]. AB - By electrophysiological methods, effect of temperature on bushcricket tympanal organ functions was studied. Activity of auditory receptors was recorded intracellularly in the 5th nerve of I thoracic ganglion in Tettigonia cantans, Metrioptera roeselii, M. bicolor, Platycleis albopunctata, Pholidoptera griseoaptera, and Phaneroptera falcata. The temperature was changed in the range from 17 to 34 degrees C. Heating of the tympanal organ to 30-32 degrees C led to a decrease of impulse amplitude, shortening of their duration, an increase of sensitivity, of the burst instantaneous frequency, and of the number of impulses in responses as well as to a decrease of latent periods (LP) of receptor reaction. The optimal frequency in all studied cells did not change, although range of perceived frequencies was enlarged. The frequency threshold curve of receptors either was shifted down along the ordinate scale without changes of its shape or the thresholds at various frequencies decreased non-uniformly. Thus, the obtained data indicate the absence of changes in the frequency tuning of the auditory receptors with changes of temperature. PMID- 17725033 TI - [Coupled evolution of digestive, respiratory, circulatory, and excretory systems: a model investigation]. AB - A model is developed of evolution of an organism with digestive, respiratory, circulatory, and excretory systems at the single system. The model is realized on the basis of the language STELLA 8.0. A balance is found between perfection of each individual physiological system and necessary energy expenditures for survival of the organism as a whole. The model is based on a coupled development of several visceral systems. There is analyzed effect of a change of consumption of substances with food and of oxygen amount on their oxidation, a branching of blood flow to organs, specifically to kidneys, to excrete final products of metabolism from blood. The energy expenditures for circulation are believed to be proportional to blood flow in a given organ. An increase of efficiency of renal excretion from blood of final metabolic products and toxic substances has a favorable effect on inner medium and activity of each cell of an individual, but increases of the organism energy expenditures. Interrelation of these factors under conditions of adaptation to changing environmental conditions determines peculiarities of evolution of each physiological system in an individual. PMID- 17725034 TI - [Organization of olfactory system of the Indian major carp Labeo rohita (Ham.): a study using scanning and transmission microscopy]. AB - Catla catla, Labeo rohita, and Cirrhinus mrigala are important alimentary fish in India. Their reproduction (breeding) depends on season. The fish perceive external factors-stimuli and chemical signals through the olfactory system that plays the key role in the central regulation of reproduction. However, in the available literature, any electron microscopy data on organization of olfactory elements in these fish are absent. We have studied ultrastructure of the olfactory organ in male L. rohita by using scanning (SEM) and transmission electron microscopy (TEM). The olfactory organ consists of olfactory epithelium, a short nerve, and olfactory bulb. The organ has oval shape and consists of approximately 47-52 lamellae in adult fish and of 14-20 lamellae in fish at the stage of fingerling. These lamellae originate from the midline raphe. By using SEM, the presence of microvillar sensory and ciliated non-sensory cells in these lamellae is shown. By using TEM, a microvillar receptor cell is revealed, which has rough endoplasmic reticulum and Golgi apparatus towards the apical end. Basal cells are found at the base of the receptor cell; supporting cells are located adjacent to olfactory receptor neurons, while epithelial cells--in the non sensory part of olfactory epithelium. Mast, blastema and macrophages cells are also found in the basal lamina. This work is the first publication on structural organization of olfactory system of the Indian major carp, which provides information about morphological and ultrastructural organization of olfactory system and opens new opportunities for study of chemical neuroanatomy, sensory signal processing, and nervous regulation of reproduction of the Indian major carp. PMID- 17725035 TI - [Postnatal changes of morphology of nerve and glial cells in neocortex of mice developing on the background of serotonin deficit]. AB - It has been shown that deficit of serotonin during embryogenesis in rodents is accompanied by changes of morphological characteristics of neurons and glial cells at the period of postnatal development. A characteristic peculiarity of these changes is cell vacuolization that is of different expression in various cortical layers. In the experimental animals as compared with control ones, neurons of all neocortex layers have changed nuclei and a reduced volume of the cytoplasm. In neurons of upper layers, nuclei and cytoplasm contain occasional small vacuoles. In deep layers, vacuolization both of nuclei and of the cytoplasm is expressed to the much greater degree and vacuoles of large size are predominant. Results of immunocytochemical study have shown that in animals developing on the background of serotonin deficit there takes place a delay of the rates of formation and differentiation of astrocytic glia. PMID- 17725036 TI - [Migration and differentiation of neurons producing gonadotropin-releasing hormone under conditions of serotonin excess in the brain of mouse embryos]. AB - The work has been carried out on mice of the Tg8 line with knockout of gene of monoamineoxidase A with an increase of serotonin and noradrenaline content in the brain, and on mice of the C3H line with unchanged genome and normal concentration of monoamines. An immunocytochemical study has been performed of development of neurons producing gonadotropin-releasing hormone (GnRH) under conditions of excess of serotonin and noradrenaline in the mice in embryogenesis. The GnRH neurons were revealed at the 18th day of embryonic development in telencephalon along trajectory of their migration from olfactory bulbs to the retrochiasmatic area. In telencephalon of mouse embryos of the Tg8 line, a redistribution of the GnRH-neurons along their migration trajectory was observed as compared with embryos of the C3H line mice. The percent of the GnRH-neurons in the Tg8 mouse embryos in caudal parts of the migration trajectory was lower than in rostral parts, the opposite distribution of the neurons being observed in the C3H line mouse embryos; at the excess of serotonin and noradrenaline in the Tg8 line mouse embryos, the total amount of GnRH-neurons in the brain was lower than in the C3H mice. In males of the Tg8 line mice under conditions of excess of serotonin and noradrenaline the optical density of neurons, which correlated with the GnRH concentration in the cell, was higher than in control mice. Thus, in the Tg8 mice under conditions of the serotonin and noradrenaline excess, migration of the GnRH neurons to their final anlage in hypothalamus is accelerated as well as the total number of the GnRH-neurons decreases, which indicates a decrease of proliferation of cells-precursors and the earlier differentiation of neurons. PMID- 17725037 TI - [NO-dependent mechanisms of ecdysterone protective action on the heart and vessels in streptozotocin-induced diabetes mellitus in rats]. AB - Ecdysterone (100 ng/100 g) chronic oral administration (2 months after STZ (5 mg/100 g) administration) normalized plasma glucose levels in rats. This potent hypoglycemic effect of ecdysterone depend on inhibition of non-constitutive NO synthesis by Ca(2+)-independent iNOS and NADP-dependent nitrate reductase as well as inhibition of L-arginine degradation by arginase result in up-regulation of Ca(2+)-dependent constitutive NO synthesis by eNOS or mithochondrial nNOS in heart and aorta of rats. PMID- 17725038 TI - [Nuclear ion channels of the granular neurons from the dentate gyrus]. AB - The nuclear envelope is a part of the endoplasmic reticulum which surrounds the genetic apparatus of the cell. Using the patch-clamp technique we have investigated ion channels in the membranes of nuclei isolated from the neurons of the dentate gyrus. Our research has shown that there is anionic (329 pS) on the outer and anionic (157 pS) and cationic (179 pS) channels on the inner nuclear membrane. Ion channels in the nuclear envelope of the neurons of the dentate gyrus differ much from ones of the neurons of the cerebellum and CA region of the hippocampus. This fact proves that different types of neurons express different sets of ion channels in the nuclear membranes. The physiological role of the ion nuclear channels in the granule cells is not clear but they may be important for the ion balance between the cytoplasm and the lumen of the nuclear envelope as well as endoplasmic reticulum of the cell if the latter represents an adequate model of granule of the some parts of ER. PMID- 17725039 TI - [Influence of enalapryl on vasomotor reactions of rats with chronic deficiency of dopamine in the mesencephalo-striatal system]. AB - The results of experiments on isolated preparations of aorta and portal vein of rats with chronic deficiency of mesencephalo-striatal dopamine have shown that endothelium-dependent reactions of dilatation were inhibited. If rats with dopamine deficiency received enalapryl (20 mg/kg) these reactions partly recovered. A possible conclusion may be that in conditions of cerebral dopamine deficiency the functional state of endothelium got worse, and endothelium dependent dilatation of vascular smooth muscles was inhibited. The use of inhibitor of angiotensin-converting enzyme enalapryl resulted in a significant restoration of the above vascular reactions. PMID- 17725040 TI - [Changes in epithelium transport system function and morphological indexes in the colon mucosa of rats with hypergastrinemia of different duration]. AB - The role of gastrin in epithelium water and electrolyte (Na+, K+, CI-) transport in comparison with mucosal morphological indexes (crypt depth, thickness of colonic mucosa and epitheliocytes nuclear profound area) was investigated by using of omeprazole-induced (OM) hypergastrinemia model (for 1-4 weeks) and in vivo perfusing technique in rats. Short-term hypergastrinemia (for 1-2 weeks) caused the alterations in electroneutral absorption of NaCl. Prolongation of hypergastrinemia influence up to 3 weeks had entailed the first manifestation of the trophic effect on colonic mucosa expressed in alterations of electrogenic sodium absorption and increased crypt depth with a thickened colonic mucosa. Prolonged OM-induced hypergastrinemia (for 4 weeks) had led to decreased colonocytes differentiation level with an increased crypt depth, a thickened colonic mucosa and decreased epitheliocytes nuclear profound area which in turn have provoked the decreasing in net water and NaCl absorption. PMID- 17725041 TI - [The synthetic cannabinoid analog WIN 55,212-2 potentiates the amplitudes of glycine-activated currents]. AB - Most of the pharmacological actions of cannabinoids are mediated by CB1 receptors. There is also evidence that these compounds can produce effects that are not mediated by the activation of identified cannabinoid receptors. Our data demonstrate that cannabinoids may directly affect the functioning of inhibitory glycine receptor (GlyR) channels. Here, we report that cannabinoid receptors agonist WIN 55,212-2, in a CB1 receptor independent manner, cause a significant potentiation of the amplitudes of glycine-activated currents (I(Gly)) in acutely isolated hippocampal CA3 and CA1 pyramidal neurons. The maximal potentiation by this compound was observed at the lowest concentration of glycine; with increasing concentrations of glycine, the potentiation significantly decreased. Also WIN 55,212-2 significantly accelerated the desensitization of Gly-induced chloride current and significantly decreased the rise time. The effects of WIN 55,212-2 on I(Gly) were not attenuated in the presence of CB1 receptor antagonist AM251, suggesting that CB1 receptor activation are not involved in action of cannabinoid on GlyRs. Altogether these data allow us to suggest the existence of a CB1R independent action of cannabinoids directly on glycine-activated currents, representing a novel antinociceptive mechanism of this compounds. PMID- 17725043 TI - [Biochemical and functional characteristics of erythrocyte membranes in sportsmens with anemia]. AB - In the article the changes of lipid-protein bilayer of erythrocyte membrane, their structural-functional particularities and activities of lipid peroxidation in interrelation with anemia's parameters in athletes. It was shown that under the intensive prolonged physical load activation of lipid peroxidation in erythrocyte membranes led to significant changes of functional parameters accompanied by increased aggregation and permeability, glycocalix sorption ability and sorption capacity along with simultaneous alteration of phospholipid and protein membrane bilayer. These membrane changes in 75% athletes accociated with anemia development which correlates with degree of biochemical and structural-functional changes in erythrocyte membrane that requires correction by antioxidant and membranoprotective therapy on stage of athletes preparation. PMID- 17725042 TI - [Characteristics of hypothyroidism correction and lipid metabolism disorder in iodine deficiency]. AB - The serum biochemical indexes (level of triiodthyronine, thyroxin, thyrothropic hormone of adenohypophysis, level of cholesterol, triglycerides) and the level of iodine excretion with urine in rats with hypothyrosis corrected by "Iodid-100" and along with excessive intake of chlorine and fluorine ions into the organism had been studied. It has been revealed that hypothyrosis has negative influence on lipid metabolism indexes. "Iodid- 100" usage stabilized hormonal and lipid status. Excessive intake of chlorine and fluorine ions by the organism decreased the effectiveness of iodine containing drugs. PMID- 17725044 TI - [Action of the red and infrared electromagnetic waves of light-emitting diodes on the behavioral manifestation of somatic pain]. AB - Research of analgesic action of electromagnetic waves (EMWs) of red (1 = 640 +/- 30 nm) and infra-red (1 = 880 +/- 30 nm) light-emitting diodes of device "MEDOLIGHT" on a tonic and acute pain of white outbreed male mice is carried out. The tonic pain was caused by hypodermic injection of 20 ml of 5% formalin solution in a back surface pad of a hinder leg. Acupuncture point (AP) E-36 or the center of pain were exposed to the action of red or infrared light-emitting diodes in cumulative density of steam radiation capacity during 10 min by 26 mWt/ cm2 in continuous or pulse regimen for frequencies 10, 600, 8000 Hz. Quantitative intensity of a painful syndrome was estimated by average group duration or quantity of painful (licking of the center of a pain, twitching of a hinder leg) and non-painful (dream, grooming, eating) behaviour manifistation of animals for the certain intervals of observation. Sensitivity of animals to acute pain--"a painful threshold"--was deter- mined in experiences with "an electric floor" on size of the electric voltage caused vocalization. The analgesic action both continuous, and pulse light-emitting diode EMWs, features of their action in relation to the place of the application and modes of influence were shown. Thus, the continuous stimulation of AP E-36 only by red EMW decreased the duration of pain paw licking on 33% and quantities of twitching of animals paw on 37% while the duration of grooming, dream, and consumption of feed raised. Such changes of painful and nonpainful behaviour unequivocally specify reduction of a tonic pain. Combined action of red and infrared EMWs caused diverse changes of painful reactions of animals and increase of extremity hyperemia. Thus at summary action of EMWs on AP E-36 of mice the long increase of painful sensitivity was observed. Exposure of EMWs to the center of a pain reduced the intensity of painful reactions of mice on 30% in average, time of their movings in a cage increased twice and duration of dream increased by 39%. Thus, summary action of red and infrared EMWs on AP E-36 promoted only to improvement of a blood circulation and increase painful sensitivity. In experiments with a tonic pain the summary pulse action on AP E-36 of the red and infrared EMWs with frequencies 10, 600, 8000 Hz reduced twice quantity of paw twitchings of animals with pain. The greatest efficiency in suppression of tonic pain syndrome observed for frequencies of 10 and 8000 Hz. The data received testify that the hypoanalgesic effect of light emitting diode EMWs depends on area of influence, lengths of wave and the modes of an irradiation chosen in view of intensity and duration of stimulation. PMID- 17725045 TI - [Prolonged after-potentials of the myelinated nervous fibres in amphibia after 4 aminopyridine-induced blockage of potassium channels]. AB - Myelinated nerve fibres of Rana ridibunda Pallas were studied by using extra cellular recording technique. 4-aminopyridine, a blocker of fast potassium channels produced considerable changes in duration of the after-depolarization and increase in total membrane depolarization (evaluated by an action potential area). These effects were time-dependent. The after-depolarization duration under 4-aminopyridine (4-AP) treatment changes in 3 phases: at the beginning of the exposure its duration increased; then the increase stopped; and later duration of the after-depolarization start to decrease. The last phase was often followed by hyperpolarizing after-potential. The interchange of these phases accompanies by statistically significant increase of the action potential area (from 189.201 +/- 28.437 m x ms in normal solution to 489.945 +/- 41.75 m x ms in 5 minutes after 4 AP application). These observations are explained as a result of the increased activation of the slow potassium channels and decreased portion of fast potassium channels involved in membrane repolarization. The decrease in post-tetanic depolarization duration, the appearance of the post-tetanic hyperpolarization at low frequencies and increase of post-tetanic hyperpolarization at higher frequencies of stimulation under 4-AP treatment are dependent on activation of slow potassium channels. PMID- 17725046 TI - [Functional and metabolic basis of sodium nitrite modulatory influence in the brain in hemic hypoxia]. AB - Free radical homeostasis parameters of rat's brain mitochondria under conditions of sodium nitrite administration at the peak of hypoxia had been studied. Prior to study experimental animals have been divided into two groups depending on resistance to hypobaric hypoxia. In brain mitochondria of high-resistant to hypoxia rats increase of the nitrites-ions contents and also intensification of pro- and antioxidative processes were registered in comparison with the control group. Decrease of all investgated free radical homeostasis parameters in brain mitochondria of low-resistant to hypoxia animals in comparison with the control group was determined. Administration of pro-hypoxic factor in toxic dose allowed us to reveal specific peculiarities of redox processes development in the brain mitochondria of experimental animals with different resistance to hypoxia. PMID- 17725047 TI - [Correction of the endothelial function damaged by gamma-irradiation with free and liposomal quercetin]. AB - It has been investigation the action of solubil quercetin (corvitin) and quercetin filled liposomes (lipoflavon) on endothelium--dependent r-irradiated isolated rats aortic rings relaxations to acetylcholine. It has been showed, that corvitin addition directly to the buffer solution (0.1 mg/ml) increase endothelium--dependent vascular responses to acetylcholine on 35%, lipoflavon addition--on 25%. PMID- 17725048 TI - [Cytokines and their role in reproductive system]. AB - In this review we analyze the involvement of cytokines in regulation of ovarian function. A growing body of evidence suggests that the ovary is a site of inflammatory reactions. Immune-competent cells present within the ovary may constitute potential in-situ modulators of ovarian function that act through local secretion of regulatory soluble factors cytokines. In addition many over cell in the ovary also produce cytokines independently of the presence of leukocytes, thus ovaries are sites of cytokine action and production. There are many evidences that cytokines are involved in the ovarian control of follicular development and are surveyed as the important regulators of steroidogenesis and gamete production. It is established that cytokines generally inhibit gonadotropin-stimulated production of steroids. However ovarian steroids, in turn, reduce the cytokine production by immunecompetent cells. There are some data about participation of cytokines in regulating the proliferation and differentiation of granulose cells. Most cytokines appear in mammalian follicles only a short time before ovulation and play the important role in process of ovulation and luteinization. Thus a variety of clinical situations may be due to cytokine action in the gonads, and therapeutic manipulation of the immune system may affect reproductive function. Moreover the findings about the expression of some cytokines by oocytes and their presence in follicular fluid provide further evidence and substantiate the physiologic role for their in ovarian function, and may lead to clinical applications in programs of in vitro fertilization and in diagnosis and treatment of infertility in women, especially in cases attributed to ovarian dysfunction. PMID- 17725049 TI - Stochastic matching and the voluntary nature of choice. AB - Attempts to characterize voluntary behavior have been ongoing for thousands of years. We provide experimental evidence that judgments of volition are based upon distributions of responses in relation to obtained rewards. Participants watched as responses, said to be made by "actors," appeared on a computer screen. The participant's task was to estimate how well each actor represented the voluntary choices emitted by a real person. In actuality, all actors' responses were generated by algorithms based on Baum's (1979) generalized matching function. We systematically varied the exponent values (sensitivity parameter) of these algorithms: some actors matched response proportions to received reinforcer proportions, others overmatched (predominantly chose the highest-valued alternative), and yet others undermatched (chose relatively equally among the alternatives). In each of five experiments, we found that the matchingactor's responses were judged most closely to approximate voluntary choice. We found also that judgments of high volition depended upon stochastic (or probabilistic) generation. Thus, stochastic responses that match reinforcer proportions best represent voluntary human choice. PMID- 17725050 TI - Response induction during the acquisition and maintenance of lever pressing with delayed reinforcement. AB - The acquisition of lever pressing by rats and the occurrence of unreinforced presses at a location different from that of the reinforced response were studied using different delays of reinforcement. An experimental chamber containing seven identical adjoining levers was used. Only presses on the central (operative) lever produced food pellets. Groups of 3 rats were exposed to one of seven different tandem random-interval (RI) fixed-time (FT) schedules. The average RI duration was the complement of the FT duration such that their sum yielded a nominal 32-s interreinforcement interval on average. Response rate on the operative lever decreased as the FT value was lengthened. The spatial distribution of responses on the seven levers converged on the operative lever when the FT was 0 or 2 s and spread across the seven levers as the FT value was lengthened to 16 or 32 s. Presses on the seven levers were infrequent during the FT schedule. Both operative- and inoperative-lever pressing intertwined in repetitive patterns that were consistent within subjects but differed between subjects. These findings suggest that reinforcer delay determined the response induction gradient. PMID- 17725052 TI - Choice in a successive-encounters procedure and hyperbolic decay of reinforcement. AB - Pigeons responded in a successive-encounters procedure that consisted of a search state, a choice state, and a handling state. The search state was either a fixed interval or mixed-interval schedule presented on the center key of a three-key chamber. Upon completion of the search state, the choice state was presented, in which the center key was off and the two side keys were lit. A pigeon could either accept a delay followed by food (by pecking the right key) or reject this option and return to the search state (by pecking the left key). During the choice state, a red right key represented the long alternative (a long handling delay followed by food), and a green right key represented the short alternative (a short handling delay followed by food). In some conditions, both the short and long alternatives were fixed-time schedules, and in other conditions both were mixed-time schedules. Contrary to the predictions of both optimal foraging theory and delay-reduction theory, the percentage of trials on which pigeons accepted the long alternative depended on whether the search and handling schedules were fixed or mixed. They were more likely to accept the long alternative when the search states were fixed-interval rather than mixed-interval schedules, and more likely to reject the long alternative when the handling states were fixed-time rather than mixed-time schedules. This pattern of results was in qualitative agreement with the predictions of the hyperbolic-decay model, which states that the value of a reinforcer is inversely related to the delay between a choice response and reinforcer delivery. PMID- 17725051 TI - Discriminated timeout avoidance in pigeons: the roles of added stimuli. AB - Two experiments examined pigeons' postponement of a signaled extinction period, or timeout (TO), from an ongoing schedule of response-dependent food delivery. A concurrent-operant procedure was used in which responses on one (food) key produced food according to a variable-interval schedule and responses on a second (postponement) key delayed the next scheduled TO according to a response-TO (R TO) interval. A series of response-independent stimulus changes on the food key temporally partitioned the R-TO into three equal segments (S1, S2, and S3). Postponement responses, in addition to postponing TO, also reinstated S1, the stimulus correlated with the greatest temporal distance from TO. In Experiment 1, the R-TO interval was manipulated systematically across blocks of sessions (conditions) at a given ratio of R-TO:TO duration. This R-TO:TO ratio was manipulated across blocks of conditions (phases). Postponement response rates varied inversely with R-TO interval in each phase. Changes in the R-TO:TO ratio did not produce consistent differences except at the 1:10 ratio for some pigeons, where it disrupted postponement responding in some conditions. Most of the postponement responses occurred in the presence of S2 and S3, the stimuli most proximal to TO, whereas most of the food-key responses occurred in S1. In Experiment 2, the R-TO contingencies were systematically manipulated in the presence of the time-correlated stimuli. In one set of conditions, the R-TO contingencies were made either ineffective or less effective in the presence of one or more stimuli. Postponement responses typically shifted to stimuli in the presence of which responses were relatively more effective. Postponement responses decreased markedly when the added stimuli were removed, and then recovered when the stimuli were reinstated. Results from both experiments indicate that the added stimuli in a discriminated TO-avoidance procedure serve predominately discriminative functions, delineating periods during which behavior is maximally effective. The results parallel those obtained in shock-avoidance procedures, providing further evidence that TO functions as an aversive stimulus. PMID- 17725053 TI - Contextual control by function and form of transfer of functions. AB - This study investigated conditions leading to contextual control by stimulus topography over transfer of functions. Three 4-member stimulus equivalence classes, each consisting of four (A, B, C, D) topographically distinct visual stimuli, were established for 5 college students. Across classes, designated A stimuli were open-ended linear figures, B stimuli were circular, C stimuli three sided, and D stimuli four-sided. Three different computer tasks then were trained with the B stimuli. Differential reinforcement and punishment procedures were then used to establish control over function transfer by the topography of the class members. For Task 1, function transfer, responding to C and D stimuli as subjects had to B stimuli, was reinforced. For Task 2, function transfer was reinforced for C stimuli but punished for D stimuli. For Task 3, function transfer was punished for both C and D stimuli. New equivalence classes were then established and tests for generalized contextual control were presented. All 5 subjects showed generalized contextual control of transfer of functions by stimulus topography. Implications of contextual control over function transfer in natural settings are discussed. PMID- 17725054 TI - Time to completion of web-based physics problems with tutoring. AB - We studied students performing a complex learning task, that of solving multipart physics problems with interactive tutoring on the web. We extracted the rate of completion and fraction completed as a function of time on task by retrospectively analyzing the log of student-tutor interactions. There was a spontaneous division of students into three groups, the central (and largest) group (about 65% of the students) being those who solved the problem in real time after multiple interactions with the tutorial program (primarily receiving feedback to submitted wrong answers and requesting hints). This group displayed a sigmoidal fraction-completed curve as a function of logarithmic time. The sigmoidal shape is qualitatively flatter for problems that do not include hints and wrong-answer responses. We argue that the group of students who respond quickly (about 10% of the students) is obtaining the answer from some outside source. The third group (about 25% of the students) represents those who interrupt their solution, presumably to work offline or to obtain outside help. PMID- 17725055 TI - Autoshaping and automaintenance: a neural-network approach. AB - This article presents an interpretation of autoshaping, and positive and negative automaintenance, based on a neural-network model. The model makes no distinction between operant and respondent learning mechanisms, and takes into account knowledge of hippocampal and dopaminergic systems. Four simulations were run, each one using an A-B-A design and four instances of feedfoward architectures. In A, networks received a positive contingency between inputs that simulated a conditioned stimulus (CS) and an input that simulated an unconditioned stimulus (US). Responding was simulated as an output activation that was neither elicited by nor required for the US. B was an omission-training procedure. Response directedness was defined as sensory feedback from responding, simulated as a dependence of other inputs on responding. In Simulation 1, the phenomena were simulated with a fully connected architecture and maximally intense response feedback. The other simulations used a partially connected architecture without competition between CS and response feedback. In Simulation 2, a maximally intense feedback resulted in substantial autoshaping and automaintenance. In Simulation 3, eliminating response feedback interfered substantially with autoshaping and automaintenance. In Simulation 4, intermediate autoshaping and automaintenance resulted from an intermediate response feedback. Implications for the operant-respondent distinction and the behavior-neuroscience relation are discussed. PMID- 17725057 TI - Patchy eczema of elderly patients. PMID- 17725056 TI - Within-trial contrast: pigeons prefer conditioned reinforcers that follow a relatively more rather than a less aversive event. AB - When behavior suggests that the value of a reinforcer depends inversely on the value of the events that precede or follow it, the behavior has been described as a contrast effect. Three major forms of contrast have been studied: incentive contrast, in which a downward (or upward) shift in the magnitude of reinforcement produces a relatively stronger downward (or upward) shift in the vigor of a response; anticipatory contrast, in which a forthcoming improvement in reinforcement results in a relative reduction in consummatory response; and behavioral contrast, in which a decrease in the probability of reinforcement in one component of a multiple schedule results in an increase in responding in an unchanged component of the schedule. Here we discuss a possible fourth kind of contrast that we call within-trial contrast because within a discrete trial, the relative value of an event has an inverse effect on the relative value of the reinforcer that follows. We show that greater effort, longer delay to reinforcement, or the absence of food all result in an increase in the preference for positive discriminative stimuli that follow (relative to less effort, shorter delay, or the presence of food). We further distinguish this within-trial contrast effect from the effects of delay reduction. A general model of this form of contrast is proposed in which the value of a primary or conditioned reinforcer depends on the change in value from the value of the event that precedes it. PMID- 17725058 TI - What is your diagnosis? Brachioradial pruritus. PMID- 17725059 TI - Cosmetic contact lenses can create diagnostic confusion. PMID- 17725060 TI - Sun sensitivity in 5 US ethnoracial groups. AB - Some sun safety activities have included only non-Hispanic white individuals, even though individuals in other ethnoracial groups may be at risk for skin cancer. The objectives of this study were to investigate distributions of self reported Fitzpatrick skin type within 5 ethnoracial groups and substantiate each group's self-report with an objective measure. The study used a cross-sectional design. The research was conducted at 70 postal stations in Southern California. Participants were US Postal Service letter carriers and included 115 Pacific Islanders, 222 black individuals, 329 Asians, 513 Hispanics, and 1364 non Hispanic white individuals. Participants self-reported skin type and had skin color measurements taken with colorimeters. Some individuals in each ethnoracial group reported having sun-sensitive skin. Correlation tests assessing the relationship between skin type and colorimeter data showed substantial associations for each group except Asians. Future sun safety research and educational messages should include all potentially high-risk individuals, irrespective of ethnoracial identity. PMID- 17725061 TI - What's eating you? Bees, Part 2: Venom immunotherapy and mastocytosis. AB - Bee stings are common in the United States. In part 1 of this series, we reviewed the characteristics of bumblebees, honeybees, and Africanized honeybees; the types and pathophysiology of sting reactions; and the medical management and prevention of bee stings. In this article, we review the concepts and practice of venom immunotherapy. We further discuss the diagnosis of systemic mastocytosis, initially presenting as anaphylaxis, and the efficacy of immunotherapy in patients with mastocytosis. PMID- 17725062 TI - Success of omalizumab as monotherapy in adult atopic dermatitis: case report and discussion of the high-affinity immunoglobulin E receptor, FcepsilonRI. AB - We report a case of a 41-year-old black man who presented with chronic severe atopic dermatitis that only responded to oral corticosteroids. Failed treatments for this patient included topical corticosteroids, topical pimecrolimus, oral prednisone, oral antihistamines, azathioprine, and narrowband UV light therapy. Only oral corticosteroids provided significant relief. The patient had an immunoglobulin E (IgE) level of 7340 IU/mL (reference range, 0-100 IU/mL). He responded to a 12-week course of omalizumab, a humanized monoclonal anti-LgE antibody currently indicated for patients 12 years and older with moderate to severe persistent asthma. Our patient experienced no adverse events throughout the course of treatment. We suggest that omalizumab may have a role in the treatment of isolated atopic dermatitis in the adult population. PMID- 17725063 TI - Blue nevi: a case report and review of the literature. AB - Blue nevi can present clinically as blue, gray, brown, or black solitary nodules or plaques on the skin. Histologically, they represent collections of melanocytes and melanophages in the dermis. We present a case of a cellular blue nevus in a 55-year-old white man that presented as an enlarging blue-gray nodule on the right dorsal foot. These cases can be challenging both clinically and histologically because malignant melanoma or malignant transformation of a blue nevus should be considered. We review the various types of blue nevi and the literature. PMID- 17725065 TI - Paintball: dermatologic injuries. AB - The popularity of paintball as an extreme sport has gained momentum in recent years. Injuries related to paintball are growing as the number of participants increases. An increasing percentage of paintball-related injuries have occurred in noncommercial settings, such as backyards. We report distinctive follicular stippling and annular scars resulting from paintball injuries in 2 males. Dermatologists may encounter paintball-related injuries during routinely scheduled visits for acne or nevi surveillance. Patients should be verbally reminded to use protective gear to prevent injuries. PMID- 17725064 TI - Botryomycosis presenting as pruritic papules in a human immunodeficiency virus positive patient. AB - Patients with human immunodeficiency virus (HIV) may present with a variety of dermatologic complaints, including reactions to medications, physiologic manifestations of their disease, numerous infectious conditions, and unusual or severe presentations of common dermatologic diseases. Botryomycosis is an uncommon infectious disorder with rare visceral involvement. The cutaneous manifestations of botryomycosis are variable and have not been well-described. We report a case of botryomycosis in an HIV-positive woman who presented with pruritic papules on her neck, trunk, and extremities. PMID- 17725066 TI - Isotretinoin as a treatment for axillary granular parakeratosis. AB - Granular parakeratosis is a condition presenting with hyperkeratotic plaques and papules that are confined to intertriginous body sites. The exact etiology is unknown, but chemical and mechanical irritation and a moist environment are potential factors. Numerous treatments have been attempted, yielding variable results. We present a case of axillary granular parakeratosis, previously unresponsive to topical treatment, that resolved after a 2-week regimen of isotretinoin. We conclude that treatment of axillary granular parakeratosis with isotretinoin is rapid and effective and should be considered in patients with no other contraindications to isotretinoin. PMID- 17725067 TI - Extensive basal cell carcinoma with probable bone metastasis. AB - Metastasis of basal cell carcinoma (BCC) rarely occurs. Few cases have been reported in the literature; those cases reported generally resulted from chronic, extensive, recurrent lesions on the head or neck. Metastases may involve lymph nodes, the lungs, and bone, as well as abdominal viscera. Once distant metastasis takes place, survival usually is short and palliative treatment is sought. With regard to bone metastases, several case reports have demonstrated similar clinical features indicative of osseous involvement. We present a case report of a patient with an extensive BCC with histologic documentation and probable bone metastasis of BCC. Clinical and radiographic features of this case were consistent with previously reported patients. However, confirmatory postmortem biopsy of the bone specimen was refused by the patient's family. PMID- 17725068 TI - Antibiotic ointment in the treatment of Grover disease. AB - Grover disease, or transient acantholytic dermatosis, chiefly affects the upper part of the trunk in men older than 40 years. Lesions may last for weeks, months, or years, and often are accompanied by intense pruritus. Some patients respond to topical steroid treatment but many do not. This article reports major or total resolution of Grover disease in 6 of 9 patients following topical application of a triple antibiotic ointment. It also proposes using a case registry as a way of further investigating the efficacy of this treatment so that dermatologists may participate. PMID- 17725069 TI - Famciclovir for cutaneous herpesvirus infections: an update and review of new single-day dosing indications. AB - Infections with herpes simplex virus (HSV) types 1 and 2 and herpes zoster are common and a substantial public health issue. Famciclovir is an effective treatment for herpes simplex and herpes zoster. We review studies evaluating the efficacy of single-day doses of famciclovir for the treatment of recurrent herpes labialis (cold sores) and genital herpes. Famciclovir has received single-day dosing indications for both of these entities. The studies leading to these new indications are reviewed. PMID- 17725070 TI - Judges', lay judges', and police officers' beliefs about factors affecting children's testimony about sexual abuse. AB - The authors examined Swedish judges', lay judges', and police officers' beliefs about factors that may complicate or facilitate children's reports of sexual abuse. Participants (N = 562) rated potential complicating and facilitating factors and freely reported which criteria they considered important when assessing the reliability of child witnesses. The groups had similar opinions regarding which factors are complicating and facilitating. Furthermore, the groups tended to regard emotional factors as more complicating than cognitive factors. When freely reporting criteria that are important when assessing reliability, judges and police officers reported criteria pertaining mainly to the child, whereas lay judges reported mainly criteria pertaining mainly to the police interview. Results indicate that participants believe that children have the capacity to remember and report about abuse but are hindered in doing so by emotional factors. Results also suggest that police officers may underestimate their own influence on the reliability of children's reports. PMID- 17725071 TI - Development and validation of the cognitive style indicator. AB - The authors describe the development and validation of the Cognitive Style Indicator (CoSI) using 3 diverse samples (N = 5,924; N = 1,580; and N = 635). Reliability, item, and factor analyses demonstrated the internal consistency and homogeneity of 3 cognitive styles: knowing, planning, and creating. The authors also found substantial support for the instrument's convergent and discriminant validity by including other cognitive style instruments and personality and academic performance measures in the validation process. Criterion-related validity was confirmed by examination of the relation between these cognitive styles and work-related characteristics. The main contributions of this study are (a) the further refinement of the analytic-intuitive cognitive style dimension by splitting the analytic pole in a knowing and a planning style and (b) the development of a valid and reliable cognitive style instrument for use in organizations. PMID- 17725072 TI - Employee satisfaction and theft: testing climate perceptions as a mediator. AB - Employee theft of both property and time is an expensive and pervasive problem for American organizations. One antecedent of theft behaviors is employee dissatisfaction, but not all dissatisfied employees engage in withdrawal or theft behaviors. The authors tested a model of theft behavior by using an organization's climate for theft as an explanatory mechanism. They found that dissatisfaction influenced employee theft behaviors through the intermediary influence of employees' individual perceptions of the organization's climate for theft. The authors encourage organizations to pay attention to such climate elements and take action to alter employee perceptions if they reflect permissive attitudes toward theft. PMID- 17725073 TI - The potency of one-to-one contact with union leaders: enhancing self-efficacy to become a union steward. AB - Finding ways to encourage union members to become union leaders is a perennial problem for unions. P. A. Roby originally found the importance of one-to-one contact with union leaders in becoming a union steward. In this study, the authors examined stewards' descriptions of their one-to-one contact with a union leader before becoming a steward. They sought to (a) replicate and strengthen Roby's findings, (b) explore one-to-one contact as a self-efficacy (i.e., confidence) enhancing experience, and (c) identify self-efficacy enhancement modes to strengthen the potency of the contact experience. The results from a mostly open-ended questionnaire of 44 stewards mirrored Roby's findings. The results indicated that self-efficacy enhancement modes were present in the one-to one contact experience and that the enhancement modes were related to self efficacy to become a steward. Two of the modes, verbal encouragement and emotional inhibition, were independently related to self-efficacy. The authors suggest how leaders could increase the potency of their contact with members as a means of encouraging members to become stewards. PMID- 17725074 TI - Change blindness and eyewitness testimony. AB - The authors explored the relevance of research on change blindness to eyewitness identification and testimony under intentional and incidental memory conditions. Participants (N = 80, 40 men and 40 women) viewed a video enactment of a burglary in which the identity of the burglar changed at the halfway point of the film. Half of participants were briefed to remember the content, and the other half were not. All were tested for the recall of the content, awareness of the change, and ability to identify either or both of the burglars. Some 61% of participants did not notice the identity change. Rates of detection were significantly higher in participants in the intentional condition, who also recalled significantly more detail from the film. Awareness of change was also significantly related to content recall scores and accuracy of identification of both burglars. The results illustrate the interrelation between the eyewitness and change blindness literatures. PMID- 17725075 TI - Cramer's model of willingness to seek counseling: a structural equation model for counseling students. AB - The author tested how well K. M. Cramer's model of willingness to seek counseling fit for master's level counseling students. Counseling students (N = 519) from across the United States completed a survey. Using structural equation modeling, the author found that Cramer's model fit with counseling students. Counseling students were most likely to report being willing to seek counseling if they had a positive attitude toward counseling, low level of self-concealment, high level of distress, and low social support. PMID- 17725076 TI - New crisis and stress management programme launched. PMID- 17725077 TI - Time of psychiatric patient assaults: fifteen-year analysis of the Assaulted Staff Action Program (ASAP). AB - An emerging literature on human-perpetrated violence suggests that seemingly apparent random acts of violence may indeed have important embedded temporal patterns. This study reviews this literature and presents the temporal findings of a fifteen-year study of patient assaults on staff in health care settings. Temporal patterns were observed for the variables of season, days of month, and shift. The reasons for these findings and their implications for health care providers are presented. A brief review of patient assaults on emergency services personnel (EMS) is outlined and this study 's findings and their implications for EMS personnel are discussed. PMID- 17725078 TI - Homicide-suicide in police families: aggression full circle. AB - Police officers are considered to be at increased risk for suicide, and such self aggression may be extended to others. This paper describes antecedents of police family homicide-suicides in a sample of 29 cases. Police experiences with violence and aggression, domestic violence, and availability of lethal weaponry are possible correlates. Results from this sample suggested that police family homicide-suicides are increasing, as approximately twice as many cases were reported in 2006 as in the two previous years. The majority of homicide victims were women (N=24; 83%), however five of the victims were men killed by women police officers. The majority of incidents occurred in younger age groups (< 40 years of age). The primary weapon employed was the police service firearm (90%). Most incidents occurred on the local police departmental level (76%) as opposed to state and federal level departments. Similar to the majority of nationwide homicide-suicides, the homicide victim was primarily a spouse or female acquaintance. In three cases a child was also killed by the perpetrator While exposure to violence in police work cannot be changed, the establishment of a strict domestic violence policy by police agencies is discussed as one strategy to reduce the incidence of violence in the police family. PMID- 17725079 TI - School violence: effective response protocols for maximum safety and minimum liability. AB - Despite the recent preoccupation with terrorism, most Americans are still killed by our own citizens, and school violence continues to be a significant source of mortality and trauma. This article describes the basic facts, features, and dynamics of school violence and presents a prevention, response, and recovery protocol adapted from the related field of workplace violence. This model may be used by educators, law enforcement professionals, and mental health clinicians in their collaborative efforts to make our academic institutions safer and healthier places to learn. PMID- 17725080 TI - Combat and Operational Stress Control. AB - Combat and Operational Stress (COS) includes all the physiological and emotional stresses encountered as a direct result of the dangers and mission demands of combat. Combat and Operational Stress Control (COSC) in the US. Army may be defined as programs developed and actions taken by military leadership to prevent, identify, and manage adverse Combat and Operational Stress Reactions (COSR) in units. This program optimizes mission performance, conserves the fighting strength, and prevents or minimizes adverse effects of COSR on Soldiers and their physical, psychological, intellectual, and social health. Its goal is to return Soldiers to duty expeditiously. COSC activities include routine screening of individuals when recruited; continued surveillance throughout military service, especially before, during, and after deployment; and continual assessment and consultation with medical and other personnel from garrison to the battlefield. PMID- 17725081 TI - Preventive psychological services in time of war: controlled coping to foster resilience. AB - The sudden onset of war results in considerable psychological challenges as well as physical danger for populations under attack. While all civilian-directed violence carries common elements of fear and threat, unexpected consequences of war often require coping strategies to be adaptive, flexible, and effective. The Hezbollah-Israel confrontation of 2006 created such unanticipated consequences for many residents of northern Israel. Although the population was experienced in dealing with years of terror and war extended stays in bomb shelters and the intensity of the attacks created additional stressors that were out of the ordinary for most residents of the war zone. We describe an intervention technique, "controlled coping, "that is designed as a first aid mechanism for such populations in similar conditions. PMID- 17725083 TI - Luring physicians with song. PMID- 17725082 TI - The effects of aerobic exercise on childhood PTSD, anxiety, and depression. AB - The purpose of the present study was to investigate the effects of aerobic exercise on childhood PTSD, depression, and anxiety. Fifteen participants, ages 14 to 17, who met DSM-IV Criteria for PTSD were recruited from an all female residential treatment center Participants engaged in an aerobic exercise program for 40 minutes, three times per week, for a total of 8 weeks. Measures included were the Children's PTSD Inventory, the UCLA Post-Traumatic Stress Disorder Reaction Index for DSM-IV, Children's Depression Inventory, and the Revised Children's Manifest Anxiety Scale. Measures were administered twice at pre intervention, again at mid-intervention, post-intervention, and at a one-month follow-up. This small n study utilized a staggered baseline, pre/post repeated measures design. Results of this study provided support for the positive effects of aerobic exercise on reducing PTSD, depression, and anxiety. Fewer participants met full criteria for PTSD after exercising. This research is a starting point toward satisfying the essential need to establish efficacious methods to treat PTSD and associated symptoms in child/adolescent populations. PMID- 17725084 TI - A sketchy profession. PMID- 17725085 TI - Where art meets science. PMID- 17725087 TI - Selected shorts. PMID- 17725086 TI - A portrait of the artist as a former surgeon. PMID- 17725088 TI - Homonymous hemianopsia. PMID- 17725089 TI - A fireman looks at sharp waves. PMID- 17725090 TI - 8 films medical students should see. PMID- 17725092 TI - Playing doctor. PMID- 17725091 TI - The history of malaria on stamps. PMID- 17725093 TI - Images and cultures: a web-based approach to teaching humanism. PMID- 17725094 TI - Hospital-treated dog bites in Minnesota, 1998-2005. AB - This paper is the first to describe the incidence of hospital-treated dog bites in Minnesota using hospital discharge data supplemented with medical record review. The rate of hospital-treated dog bites rose 40% during the 8-year period studied, with the largest growth being seen in the number of emergency department (ED) visits. The highest rates of both hospitalization and ED treatment occurred among children ages 1 to 4 years. In most instances (75%), the victim was familiar with the dog(s) involved. The dog bites most often occurred in the home (48%) and yard (18%). Our findings emphasize the importance of physicians, especially pediatricians and family physicians, counseling parents about the importance of supervising their children when they are around dogs and teaching them safe behaviors around animals. Finally, this study validates the value of hospital discharge data for surveillance of hospital-treated dog bites. PMID- 17725095 TI - Sparklers, smoke bombs, and snakes, oh my! Effect of legislation on fireworks related injuries in Minnesota, 1999-2005. AB - In 2002, Minnesota changed its law banning all fireworks and allowed for nonexplosive, nonaerial fireworks. This article reports that hospitals have seen a steady rise in the number of patients treated for injuries related to fireworks, including a 100% increase in the number of annual fireworks-related injuries between the years 1999 and 2005 based on hospital discharge data. PMID- 17725097 TI - New agents in medical oncology and the risk of venous thromboembolism. AB - Over the past several years the medical approach to cancer patients has made important steps forward both in the field of novel, selective, antiproliferative agents and more effective supportive therapies. A greater understanding of the molecular pathways regulating cell proliferation and metastasis has led to the identification of a range of targets specifically inhibited by these new drugs. The clinical development of these compounds (the so called "targeted therapies") has shown distinctive adverse effects with respect to standard chemotherapeutic agents but the potential increasing risk of venous thromboembolism remains unvaried. In fact, the incidence of this potentially life-threatening complication in patients receiving standard chemotherapy ranges from about 11% to 20% and even more depending on the type of drug administered and on the possible association with other anti-neoplastic and supportive therapies. In this paper we reviewed all the available evidences concerning the increasing risk of venous thromboembolism in cancer patients during treatment with new agents currently used in medical oncology together with data concerning the clinical value of a concomitant prophylactic anticoagulation. At present, additional information concerning safety in terms of thromboembolic risk of novel biological and molecular therapies should be collected from specifically designed original basic science studies and clinical trials in order to optimize their use in current oncology practice. PMID- 17725096 TI - Oral anticoagulation may prolong survival of a subgroup of patients with cancer: a cochrane systematic review. AB - To evaluate the effectiveness and safety of oral anticoagulants in improving survival of cancer patients. We conducted in January 2007 a comprehensive search for relevant randomized clinical trials (RCTs). We extracted data on methodological quality, participants, interventions and outcomes using a standardized form. Five RCTs fulfilled the inclusion criteria and all compared warfarin to either placebo or no intervention. Their overall methodological quality was acceptable. The effect of warfarin on mortality was not statistically significant at 6 months (RR = 0.96; 95% CI 0.80-1.16), at 1 year (RR = 0.95; 95% CI 0.86-1.05), at 2 years (RR = 0.97; 95% CI 0.87-1.08) or at 5 years (RR 0.91; 95% CI 0.83-1.01). In the subgroup of patients with small cell lung cancer (SCLC), warfarin reduced mortality at 6 months (RR = 0.69; 95% CI 0.50-0.96) but not at 1 year (RR = 0.88; 95% CI 0.77-1.01). This 6 months mortality benefit was statistically significant in the subgroup of extensive SCLC (RR = 0.65; 95% CI 0.45-0.93) but not in the subgroup of limited SCLC (RR = 0.68; 95% CI 0.36-1.28). Warfarin increased both major bleeding (RR = 4.24; 95% CI 1.85-9.68) and minor bleeding (RR = 3.34; 95% CI 1.66-6.74). The evidence suggests a survival benefit from warfarin in patients with extensive SCLC, but not in other patient groups. This survival benefit should be weighed against the increased risk for hemorrhage. PMID- 17725098 TI - Expression of genes involved in heme biosynthesis in the human retinoblastoma cell lines WERI-Rb-1 and Y79: implications for photodynamic therapy. AB - Photodynamic therapy (PDT), using protoporphyrin IX (PpIX) as a natural photosensitizer, may be a viable alternative therapy of retinoblastoma. In order to evaluate the potential value of PpIX, the expression profiles of genes involved in heme biosynthesis in human retinoblastoma WERI-Rb-1 and Y79 cells were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Expression levels were highest in protoporphyrinogen oxidase (PPOX), uroporphyrinogen synthase and aminolevulinic acid synthase. Ferrochelatase expression showed a reduction compared to PPOX. PpIX levels were 15- and 18-fold higher in WERI-Rb-1 and Y79 cells, respectively, following induction by delta aminolevulinic acid. PDT may thus be a promising treatment in vitro, at least in these two retinoblastoma cell lines. PMID- 17725099 TI - Reversing adriamycin resistance of human breast cancer cells by hyperthermia combined with Interferon alpha and Verapamil. AB - One of the major obstacles related to chemotherapy is resistance against anticancer drugs, including Adriamycin (ADM). The purpose of the present work is to investigate the reversal effects on ADM resistance by hyperthermia (42.5 degrees C) combined with two reversal agents (Interferon alpha and Verapamil) in MCF-7/ADR (ADM-resistant MCF-7 breast cancer cell line), and its relevant molecular mechanism of action. The cell survival rate and ADM IC50 of different experiment groups were measured by MTT test. The quantitative expression of MDR1 gene in cells was detected by Real-time PCR, and the expression of P-glycoprotein (P-gp) on the cells surface and the intracellular ADM accumulation was detected by flow cytometry (FCM). The ADM IC50 of the MCF-7/ADR cells decreased 830-fold after combined with Interferon alpha (IFN-alpha) and Verapamil (VRP). Although there was no distinction in the mRNA expression of MDR1, the P-gp on the MCF 7/ADR cell membrane was significantly reduced and the cellular ADM uptake increased markedly as compared to pretreatment. Our results suggeste that hyperthermia induces a considerably reversal activity against ADM resistance synergizing other reversal agents (IFN-alpha and VRP). The reversal mechanism needs further study. However, these features of hyperthermia may be exploited in clinical cancer chemotherapy. PMID- 17725100 TI - Active immunotherapy for cancer patients using tumor lysate pulsed dendritic cell vaccine: a safety study. AB - Cancer vaccine therapy represents a promising therapeutical option. Consistently, with these new treatment strategies, the use of dendritic cell vaccines is becoming increasingly widespread and currently in the forefront for cancer treatment. The purpose of this study was to evaluate the feasibility and safety of tumor lysate-pulsed dendritic cell (DC) vaccine in patients with advanced cancers. For this purpose, eighteen patients with relapsed or refractory cancer were vaccinated with peripheral monocyte-derived DCs generated with GM-CSF and IL 4, and pulsed consequently with 100 microg/ml of tumor lysate before maturation in culture in the presence of IL-1beta, PGE2 and TNF alpha for two days. The first two vaccinations were given intradermally every two weeks while further injections were given monthly. Tumor lysate-pulsed dendritic cell injections were well-tolerated in all patients with no more than grade 1 injection-related toxicity. Local inflammatory response was mainly erythematous which subsided in 48 hrs time. No end organ toxicity or autoimmune toxicity was identified. Clinical responses observed in our study were satisfactory for a phase I clinical study. We observed 4 (22%) objective clinical responses. These responses are significantly correlated with delayed type hypersensitivity testing (DTH) (p < 0.01). The results showed that this active immunotherapy is feasible, safe, and may be capable of eliciting immune responses against cancer. PMID- 17725101 TI - Loss of cytokeratin 13 expression in squamous cell carcinoma of the tongue is a possible sign for local recurrence. AB - Cytokeratin (CK) 13 is an intermediate filament protein that is expressed in a cell-type-specific manner, in the tongue and occasionally in tongue squamous cell carcinoma (SCC). Correlations between the clinical features of patients with SCC and CK13 expression in the tumor are here investigated along with CK13's utility as a marker for tongue cancer status. Samples from 121 patients with SCC of the tongue were examined by immunohistochemistry with antibodies against CK13. Correlations between the expression level of CK13 in the tumor and the patients' clinical features were statistically analyzed by univariate and multivariate methods. Univariate analysis showed a more relevant number of local recurrence (P = 0.04) in CK13-negative staining patients. In addition, CK13-negative cases were associated with local recurrence by multiple logistic regression analysis (OR: 3.36; 95% CI: 1.044-10.78; P = 0.04). Our results suggest that the loss of CK13 expression indicates tumors with a high potential for recurrence, and thus CK13 could be useful for determining the best course of treatment. PMID- 17725102 TI - Atypical thyroid nodules express both HBME-1 and Galectin-3, two phenotypic markers of papillary thyroid carcinoma. AB - Ninety-six thyroid lesions were immunohistochemically evaluated for HBME-1 and Galectin-3 expression including nodules with cytological atypia, the latter defined as nuclear features suggestive but not diagnostic of papillary thyroid carcinoma. Thirty nodules with cytological atypia, 49 papillary thyroid carcinomas (PTCs), 4 follicular carcinomas and 13 oxyphilic tumors were examined. Forty-one of the 49 PTCs, 16 atypical thyroid nodules and 3 non-malignant oxyphilic tumors exhibited a combined expression of HBME-1 and Galectin-3. In 6 of the sixteen atypical thyroid nodules the immunoreactivity for both markers was strong and diffuse, simulating the pattern observed in PTC. We conclude that thyroid nodules with cytological atypia and strong/diffuse positivity for both HBME-1 and Galectin-3, two well recognized markers of PTC, represent a starting phenotypic change towards PTC, for which a benign or borderline counterpart has not yet been defined. The expression of HBME-1 and Galectin-3 in some thyroid nodules is related to the presence of cytological atypia suggestive but not diagnostic of PTC. The phenotypic similarity between this subset of thyroid nodules with cytological atypia and PTC is also confirmed by our data according to which Galectin-3 and HBME-1 have been found to be highly sensitive for PTC. PMID- 17725104 TI - The breast dynamic contrast enhanced MRI: preliminary results of a quantitative analysis. AB - The objective of our study was to apply a quantitative analysis to the dynamic contrast enhanced MR imaging of the breast. Automated criteria increase the objectivity and reproducibility of the diagnostic interpretation of the imaging for differentiating benign and malignant lesions. The validation of this applied method was evaluated by analysing the time- signal intensity curves and the performance of the extracted enhancement parameters. The performance of some extracted parameters was evaluated by ROC (Receiver Operating Characteristic) analysis. These parameters were found to be particularly accurate in differentiating lesions. PMID- 17725103 TI - Relationship between radiation induced dicentric chromosome aberrations and micronucleus formation in human lymphocytes. AB - Chromosome damage measured by the chromosome aberration technique is a reliable method to assess the radiation dose absorbed by cells. However, this technique has some disadvantages. Scoring is difficult and requires skill and experience which of these lead low number of cell counts. The micronucleus (MN) technique which also measures chromosome losses has easy scoring criteria leading high numbers of cell counts and therefore holds more statistical power. In this study, the relationship between the results of the micronucleus technique and those obtained by the chromosome aberration technique was investigated after radiation doses of 1Gy, 2Gy, 3Gy and 4Gy to peripheral blood lymphocytes of 3 healthy individuals. Increases in the chromosome damage after radiation were observed in both techniques. When the dicentric aberration frequencies that were measured in the chromosome aberration technique and the micronucleus frequencies were compared, no difference (p > 0.05) between these two independent measures of radiation damage was reported. The relationship between the micronuclei and the free acentric chromosome aberrations measured in the chromosome aberration technique was not significant as well as that between the dicentrics and micronuclei. On the basis of the relationship between the dicentric aberrations and the micronucleus frequencies, the micronucleus technique with an easy and short-term application and with an easy scoring can be used as an alternative to the chromosome aberration technique. PMID- 17725106 TI - Novel DNA amplification on chromosomes 6q23-24 and 4p15.2 in breast cancer identified by arbitrarily primed polymerase chain reaction. AB - Breast cancer is the most common cancer among women worldwide. The molecular basis of breast cancer has not yet been fully elucidated. In this report, novel DNA amplification on chromosomes 6q23-24 and 4p15.2 were identified by arbitrarily primed polymerase chain reaction, gene cloning, nucleotide sequencing and identified by comparison with known sequences in genome data base, and quantitated by real-time PCR. Results revealed that 25 of 32 (78.1%) breast cancer cases harbored DNA amplification on chromosomes 6q23-24 and 4p15.2. There was a significant association between increase in tumor size (> 3cm) and DNA amplification on chromosome 6q23-24 (Odds ratio = 13.75, 95% CI = 1.26-350.38, P = 0.018). The results indicated that DNA amplification on chromosome 6q23-24 may be involved in the progression of breast cancer. PMID- 17725105 TI - Schedule-dependent cytotoxicity of 5-fluorouracil and irinotecan in p53 mutant human colon cancer. AB - IFL [irinotecan (CPT-11), 5-fluorouracil (5-FU), and folinic acid] is one of the treatments for metastatic colorectal cancer. We evaluated cytotoxic effects of a sequentially administered a combination of 5-FU with CPT-11 in human p53 mutant colon cancer. Sequential combination of 5-FU and CPT-11 in human colon cancer SW480 cells using a WST-8 colorimetric assay was studied. Cytotoxicity and cell cycle distribution for each drug were evaluated using an apoptosis assay and flow cytometry. Potential mechanisms of sequence-dependent cytotoxic effects were investigated using microarrays. Cytotoxicity of 5-FU (10, 100, 1000 microM) combined with subsequent use of CPT-11 (1 microM) was significantly greater than the reverse sequence of CPT-11 followed by 5-FU (p < 0.05). Following 24 hrs treatment with 5-FU (0.1-100 microM), no significant apoptosis was observed. In contrast, apoptosis was significantly induced after 24 hrs treatment with CPT-11 (1 and 10 microM). Flow cytometric analysis showed no significant difference in cell cycle distribution between different drug concentrations. We demonstrated up regulation of 85 genes and down-regulation of 21 genes correlating with sequence dependent cytotoxicities of 5-FU and CPT-11. The superiority of 5-FU-CPT-11 sequence was proven for p53 mutant colon cancer, SW480. Treatment with 5-FU followed by CPT-11 administration may be the optimal sequence for IFL treatment of metastatic colon cancers. PMID- 17725107 TI - Phospho Akt mediates multidrug resistance of gastric cancer cells through regulation of P-gp, Bcl-2 and Bax. AB - Phosphatidylinositol 3-kinase/Akt pathway is an important intracellular pathway that is frequently activated in cancer cells. The role of P-AKT in multidrug resistance of gastric cancer cells and the possible underlying mechanisms are here investigated. Up-regulation of P-AKT expression could confer resistance to both P-glycoprotein-related and P-glycoprotein-non-related drugs on AGS cells, and suppress adriamycin-induced apoptosis, along with decreased accumulation and increased releasing amount of adriamycin. P-AKT could significantly up-regulate the expression of Bcl-2, and down-regulate the expression of Bax, but not alter the expression of PTEN in gastric cancer cells. Inhibition of P-AKT expression could partially reverse P-AKT-mediated multidrug resistance and significantly up regulate P53 expression, and down-regulate the expression of P-glycoprotein and the transcription of the multidrug resistance gene 1. Further studies of the biological functions of P-AKT may be helpful for understanding the mechanisms of multidrug resistance of gastric cancer and developing possible therapeutical strategies. PMID- 17725108 TI - Expression of PCAF, p300 and Gcn5 and more highly acetylated histone H4 in pediatric tumors. AB - Any deregulation of histone acetyltransferases (HATs) could affect several processes in tumors. In this paper, the expression of the PCAF, p300 and Gcn5 HATs by RT-PCR in 34 tumor samples was evaluated. Samples of both central nervous system tumors (CNST, 13 cases) and Wilm's tumors (WT, 11 cases) over-expressed PCAF up to 1.6-, and Gcn5 up to 1.3-fold, respectively. In 9 out of 10 samples of benign tumors (BT), PCAF was not expressed. The p300 gene was the least expressed in all tumors. The medians of expression of PCAF (124.0 DU) and Gcn5 (127.0 DU) genes were higher in CNST than in both WT (102.0 and 101.0 DU, respectively) and BT (70.0 and 82.4 DU, respectively). There was a trend to decrease the expression of PCAF and Gcn5 genes in CNST, according to: chemotherapy (110.0 and 96.0 DU, respectively), chemo plus radiotherapy (124.0 and 115.0 DU, respectively) or no treatment (134.0 and 142.0 DU, respectively) in the tumors. A similar trend was observed in WT. Finally, we revealed more highly acetylated forms of histone H4 in CNST and WT. The over-expression of PCAF could represent a new molecular tumor marker in malignant tumors, especially in CNST in pediatric patients. PMID- 17725109 TI - Acral myxoinflammatory fibroblastic sarcoma of the foot. AB - We report a rare case of acral myxoinflammatory fibroblastic sarcoma (AMFS) in a 68-year-old woman. Tumor excision of a mass between the 1st and 2nd toe of the left foot was performed after a diagnosis of ganglion in February 2003. Examination of the surgical specimen confirmed AMFS. No recurrence or metastasis occurred during the follow-up period of 4 years. Clinical characteristics such as recurrence rate, metastasis rate and period of metastasis are unclear for AMFS. Long-term clinical follow-up is thus required. PMID- 17725110 TI - Hemangioblastoma of the filum terminale. Case report and review of the literature. AB - Hemangioblastomas of the filum terminale are particularly rare tumors. The authors present the case of a 62-year-old woman with a 6 month history of low back-pain, who underwent surgery for the removal of an hemangioblastoma affecting the cauda at L2-L3 level. This highly vascularized tumour is tightly adherent to the filum terminale and hence is a very challenging pathology to remove. Histologically it consisted in vascular structures interposed to a network of capillary-like vessels, surrounded by stromal cells. MRI, angiography with pre surgical embolization, and radical surgery represent the focal points in the diagnosis and treatment of these tumours. The most relevant literature has been carefully reviewed. PMID- 17725111 TI - An unusual case of a solitary pulmonary nodule associated with an abscess correctly distinguished by Pet/Ct fusion imaging. AB - The case of a male patient affected by concomitant solitary pulmonary nodule and chest abscess located on the same side and each close to the other is reported. The importance in differential diagnosis of these two lesions obtained by the 18F FDG PET/CT fusion imaging examination is discussed. PMID- 17725113 TI - Carry out your visions and dreams. PMID- 17725112 TI - Concomitant occurrence of a primary renal NHL and of a papillary urothelial ureter cancer. AB - In this manuscript for the first time we describe the concomitant diagnosis of primary renal non-Hodgkin lymphoma (PRL) and of a papillary urothelial cancer in a patient with megaloblastic anemia. PRL is a rare disease, since the kidney is one of the extranodal organs usually not containing lymphoid tissue. The disease usually affects adults with an average age of 60 years and slight male preponderance. Flank pain is the most common presenting symptom and different histologies have been reported. A review of literature indicated that simultaneous diagnosis of PRL and papillary urothelial carcinoma of the urether, makes our case unique. The early diagnosis of both diseases allowed the eradication of the two neoplasms by nephro-ureterecthomy and by performing subsequent systemic chemotherapy. PMID- 17725114 TI - Midwifery model of care--childbirth education: shifting the paradigm. PMID- 17725115 TI - Marion's message: too many or not enough cesarean sections? PMID- 17725116 TI - The enduring qualities in midwifery. PMID- 17725117 TI - Timeless tradition. PMID- 17725118 TI - The target of the bully and the effects of PTSD. PMID- 17725119 TI - Management or care: different outcomes. AB - Recently a popular magazine published a birth story of a long, medically managed, first labor of a low-risk woman, which ended in a cesarean. (1) The doctor/writer was convinced that the labor could not be safely managed other than how he described it and that no safe alternative existed to a cesarean delivery. This is another example of the media trend of promoting medical birth stories and not midwifery-supported birth stories. The article below provides two versions of the same woman's labor to show how a woman's choice of birth attendant and labor support can influence the course of labor and the likelihood of cesarean surgery. judyslome@hotmail.com. PMID- 17725120 TI - Save time and effort--and make more money--with electronic communication. PMID- 17725121 TI - Birth of hope. PMID- 17725122 TI - Trends vs. traditions. PMID- 17725123 TI - The challenges and rewards of life as an apprentice. PMID- 17725124 TI - Birthing with reverence. PMID- 17725125 TI - Healing honey. PMID- 17725126 TI - Trends versus tradition in cesarean surgery: effects on midwifery practice and cesarean mothers' future pregnancies. PMID- 17725127 TI - Story of a VBAC rupture. PMID- 17725128 TI - Leaving the care of my midwives. PMID- 17725129 TI - A work-toward solution to the American obstetrical crisis. PMID- 17725130 TI - Chlorhexidine as an alternative treatment for prevention of group B streptococcal disease. PMID- 17725131 TI - Go tell it: using media to educate about birth. PMID- 17725132 TI - Reflections on the end of a career. PMID- 17725133 TI - The business of midwifery: the financial plan for commercial insurance. PMID- 17725134 TI - Mobilizing global midwives: The story of baby Elisha. PMID- 17725137 TI - Traditional midwives are midwives. PMID- 17725136 TI - Insurance and British midwifery: the end of independent midwifery in the UK? PMID- 17725135 TI - Yunnan Paiyao: postpartum friend. PMID- 17725138 TI - A comparative study of early postoperative feeding versus conventional feeding for patients undergoing cesarean section; a randomized controlled trial. AB - OBJECTIVE: To compare the efficacy and side effects of early postoperative feeding versus conventional feeding for patients undergoing cesarean section. MATERIAL AND METHOD: Women undertaking uncomplicated cesarean section under regional anesthesia were randomly assigned to early feeding or conventional feeding groups. Early-fed women were offered a liquid diet within 8 hours after surgery, advanced to a soft diet on the next meal and then a regular diet. Conventional-fed women were prohibited from mouth-fed for the first 24 hours after surgery, advanced to a liquid diet on the first postoperative day, and then a soft diet on the second postoperative day. RESULTS: Two hundred patients were enrolled in the study; 107 patients were assigned to the early feeding group and 93 patients to the conventional feeding group. There were no significant differences in the demographic data between the two groups. In all cases, consistent anesthetic method was applied with no intraoperative adhesion and no post operative complications were observed. The rate of mild ileus symptoms in the early feeding group was significantly less than the conventional group (19.6% versus 31.1%, p = 0.03). The early feeding group also had significantly shorter time interval to bowel movement (16.7 hours versus 25.3 hours, p < 0.001), duration of intravenous fluid administration (20.5 hours versus 24.8 hours, p < 0.001), and overall length of hospital stays (3.3 days versus 4.0 days, p < 0.001). CONCLUSION: The study results indicated that the early feeding after uncomplicated cesarean section had reduced the rate of ileus symptoms and offer potential benefits associated with shorter interval to bowel movement, intravenous fluid administration, and length of hospital stays. However, management of postoperative feeding requires proper counseling on details of both regimens and flexibilities should be provided to accommodate early feeding when requested by the patients. PMID- 17725139 TI - Adverse pregnancy outcomes in gestational diabetes mellitus. AB - OBJECTIVE: To evaluate adverse pregnancy outcome in women diagnosed with gestational diabetes mellitus (GDM) at Siriraj hospital. STUDY DESIGN: Cross- sectional study. SETTING: Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University. MATERIAL AND METHOD: One hundred and sixty two women who were diagnosed with GDM and who received treatment following clinical practice guideline at Siriraj hospital were enrolled. Data were abstracted from medical record regarding adverse pregnancy outcomes of both the mothers and their infants. RESULTS: The most common clinical risk for GDM was age > or = 30 years (116 cases, 71.6%), followed by family history of diabetes mellitus (81 cases, 50%) and obesity (47 cases, 29%). Majority of the women were GDM class A1 (156 cases, 96.3%) and only six cases (3.7%) were GDM class A2. Maternal complications were found in 35 cases (21.6%) and the most common complications were postpartum hemorrhage (17 cases, 10.5%), mild preeclampsia (6 cases, 3.7%) and severe preeclampsia (3 cases, 1.9%). The most common neonatal complication was hypoglycemia (111 cases, 68.5%). This occurred in all infant of GDM class A2 mothers. Macrosomia was found in 29 cases (17.9%). No significant differences in maternal and neonatal complications were found between GDM class A1 and class A2. CONCLUSION: Women with GDM who were diagnosed and treated following treatment guidelines demonstrated no severe maternal and neonatal complications. PMID- 17725140 TI - Antiemetic effect of ondansetron and dexamethasone in gynecologic malignant patients receiving chemotherapy. AB - OBJECTIVES: To evaluate the antiemetic effect of a single dose of ondansetron and dexamethasone as a prophylaxis for chemotherapy induced acute nausea and emesis and factors associated with the control of acute nausea and emesis. MATERIAL AND METHOD: Patients who received single dose of 8 mg ondansetron and 20 mg dexamethasone as a prophylaxis for chemotherapy induced nausea and emesis at Department of Obstetrics and Gynecology, Bangkok Metropolitan Administration Medical College and Vajira Hospital, between October 2004 and April 2006 were identified. The assessment record of the drug efficacy had been evaluated in the first 24 hours after the start of chemotherapy in terms of control of vomiting, and nausea. Age of the patients, history of alcohol intake, type of cancer, regimen of chemotherapy and course of chemotherapy were analysed as possible factors associated with the control of nausea and emesis. RESULTS: Seventy-eight gynecologic-cancer patients receiving 353 cycles of chemotherapy were evaluated in this study. Completed control of acute vomiting and nausea were 68% and 57.2% respectively. Complete control of acute vomiting and nausea were 56.9% and 45.4% in patients of < or = 45 years compared to 78.8% and 68.7% in those with > 45 years. Complete control of acute vomiting and nausea were 59.2% and 48.7% in those receiving cisplatin-containing regimens compared to 86.7% and 75.2% in non cisplatin containing regimens. Univariable and multivariable analysis showed that younger patients and those who received cisplatin-containing regimens had significant lower rates of complete control of both nausea and emesis. Patients receiving the first three courses of chemotherapy had significantly higher rate of complete control of nausea but not emesis as compared to those receiving chemotherapy after the third course. CONCLUSION: A single intravenous dose of 8 mg of ondansetron and 20 mg of dexamethasone had good control of acute nausea and vomiting only in those who received non-cisplatin containing regimens and those older than 45 years. PMID- 17725141 TI - First 4-hour urinary protein - creatinine ratio for diagnosis of significant proteinuria in preeclampsia. AB - OBJECTIVE: To evaluate the diagnostic accuracy of the first 4-hour urinary protein - creatinine ratio for prediction of the significant proteinuria in preeclampsia. STUDY DESIGN: Diagnostic test SUBJECTS: One hundred and sixty-four pregnant women who were initially diagnosed with hypertensive disorder and hospitalized in the obstetric ward and labor room at Bangkok Metropolitan Administration Medical Collage and Vajira Hospital between July 2005 and April 2006. MATERIAL AND METHOD: Urine samples were collected within 24 hours in two consecutive periods: the first 4 hours and the next 20 hours. The urine volume, urine protein and creatinine concentration were separately measured and the first 4-hour urinary protein - creatinine ratio were calculated. With the use of a protein level > or = 300 mg in 24 hours urine collection as the gold standard, the sensitivity and specificity of the first 4-hour urinary protein-creatinine ratio for diagnosis of significant proteinuria were determined with cutoffs range. RESULTS: One hundred and sixty four patients were recruited for this study including 112 patients (68.3%) who had preeclampsia. The first 4-hour urinary protein-creatinine ratio was most accurate for diagnosis of preeclampsia is 0.30 with 81% sensitivity, 88% specificity, PPV of 93%, and NPV of 71%. CONCLUSION: The first 4-hour urinary protein-creatinine ratio at 0.3 is the most accurate value for diagnosis of significant proteinuria in preeclampsia PMID- 17725142 TI - Outcome of idiopathic thrombocytopenic purpura in pregnancy in King Chulalongkorn Memorial Hospital. AB - OBJECTIVE: To study the maternal and fetal outcome of idiopathic thrombocytopenic purpura (ITP) in pregnancy. MATERIAL AND METHOD: The medical records of women who were diagnosed to be idiopathic thrombocytopenic purpura during and before pregnancy from January 1995 to December 2004 were reviewed. RESULTS: There were 33pregnancies from 29 ITP women as four women had two pregnancies each and one was twins. Nine cases (27.3%) were active ITP, five cases (15.2%) were relapsing ITP and eight cases (24.2%) were inactive ITP. Eleven cases (33.3%) had severe thrombocytopenia during delivery and five neonates (23.8%) had severe thrombocytopenia. There was no statistical correlation between maternal and neonatal platelet concentration (r = -0.0601). None of the mothers and fetuses had serious hemorrhagic complication such as intracranial hemorrhage. CONCLUSION: There were low hemorrhagic risks in both mothers and infants because of the constant monitoring of multidisciplinary groups of experienced physicians, including obstetricians, hematologists, anesthesiologists and neonatologist. PMID- 17725143 TI - Pregnancy outcome of twin pregnancy in Ramathibodi Hospital. AB - OBJECTIVES: To evaluate maternal and neonatal complications and pregnancy outcomes of twin pregnancies. MATERIAL AND METHOD: The retrospective analysis included data on the twin pregnancies delivered at Ramathibodi Hospital between January 1995 and December 2000. The data retrieved from the medical records included demographic data, complications of pregnancy, and maternal and neonatal outcomes. Statistical analysis was performed. RESULTS: Of 374 twin pregnancies, 321 cases had completed medical records. Incidence of twin pregnancies was 8.6 per 1,000 births. Most common maternal complication was preterm delivery (49.2%). Other maternal complications were anemia (21.5%), pregnancy induced hypertension (13.4%), premature rupture of membranes (10%), postpartum hemorrhage (5.6%) and antepartum haemorrhage (1.9%), respectively. Median gestational age at delivery was 37 weeks. Most common route of delivery was caesarean section (58.3%). Most common neonatal complication was low birth weight (62.3%). Perinatal mortality rate was 45 per 1,000 births. Prematurity was the most common cause of neonatal death. No neonatal death was found after 34 weeks of gestation. CONCLUSION: Twin pregnancy has high maternal and neonatal complications, especially preterm delivery that increases risk of significant neonatal morbidity and mortality. PMID- 17725144 TI - Pregnancy outcomes of multiple repeated cesarean sections in King Chulalongkorn Memorial Hospital. AB - OBJECTIVES: To determine the incidence of maternal and neonatal morbidity and mortality in women with history of at least one previous cesarean section and to compare the pregnancy outcome of the women with the history of one previous cesarean section to the women with the history of two or more previous cesarean section. MATERIAL AND METHOD: We performed a retrospective study of 458 patients undergoing repeated cesarean section from 1998 to 2005. Various factors that may be associated with repeated cesarean sections and pregnancy outcomes were assessed and analyzed. RESULTS: Maternal morbidity rate was 18.6%, including operative complications (17.5%) and post operative complications (1.7%). The operative complications included intraperitoneal adhesion 45 cases (9.8%), excessive blood loss (> 1000 ml) 29 cases (6.3%), placenta previa 5 cases (1.1%), placenta adherens 6 cases (1.3%) and requirement of blood transfusion 10 cases (2.2%). Postoperative complications included postpartum hemorrhage 4 cases (0.9%). No maternal mortality was found in this study. Neonatal morbidity rate was 20.5%, including neonatal jaundice 33 case (7.20), large for gestational age 37 cases (8.1%), and preterm babies 20 cases (4.4%). There were no statistically significant differences of maternal morbidity and neonatal morbidity between the pregnant women with the history of one previous cesarean section and the women with the history of two or more previous cesarean section. CONCLUSIONS: Maternal and neonatal morbidity in repeated cesarean section were low. PMID- 17725145 TI - Prenatal prevention for severe thalassemia disease at Srinagarind Hospital. AB - OBJECTIVE: To evaluate the results and cost-effectiveness of prenatal prevention measurement in severe thalassemia diseases at Srinagarind Hospital. STUDY DESIGN: Descriptive study. SETTING: Antenatal care (ANC) Clinic, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University. SUBJECTS: 1,498 thalassemic screened pregnant women first presenting at ANC Clinic at gestational age less than 17 weeks. MATERIAL AND METHOD: Medical records of thalassemic screened pregnant women between February 2002 and February 2005 were analyzed. Those with a value of mean corpuscular volume (MCV) less than 80 fl, or positive dichlorophenol indophenol precipitation test (KKU-DCIP Clear Reagent Kit) underwent hemoglobin (Hb) typing by high performance liquid chromatography (HPLC) together with thalassemia investigation (complete blood count, MCV and Hb typing) of their husbands and to identify couples at risk of 3 severe thalassemia diseases; Hb Bart's hydrops fetalis, homozygous, -thalassemia and, -thalassemia/ Hb E disease. Then they were advised to undergo DNA analysis and, if they had fetal risk, appropriate prenatal diagnosis was offered. MAIN OUTCOME MEASURE: Number of affected fetuses detected by prenatal diagnosis. RESULTS: Nine hundred and ninety six pregnant women (66.49%) were positive on screening. Of these, 642 (64.46%) had thalassemia investigation done with their spouses. There were 19 couples at risk (1.27% of total screened pregnant women) for having fetal severe thalassemia disease from initial laboratory results. Most of them were, -thalassemia/ Hb E diseases. We found only 10 pregnant women (52.63%) that had undergone prenatal diagnosis. The consequent results were two affected fetuses (20%), one was Hb Bart's hydrops fetalis, and the other was, o-thalassemia/ Hb E disease. In these cases, their parents decided to discontinue the pregnancy. Our prevention program could save 1.14 million bahts for the cost of treatment in two prevented severe thalassemia cases. CONCLUSION: The prenatal prevention program of severe thalassemia disease at Srinagarind Hospital can effectively detect affected fetuses and reduce severe thalassemia disease, which is a major health problem in Thailand. PMID- 17725146 TI - Risk factors for cesarean hysterectomy in cesarean delivery. AB - OBJECTIVE: To identify the risk factors for cesarean hysterectomy. MATERIAL AND METHOD: A case-control study was conducted by reviewing the medical records of pregnant women delivered in King Chulalongkorn Memorial Hospital between January 1994 and December 2004. Cases included pregnant women who underwent hysterectomy immediately or within 24 hours after cesarean delivery, whereas control referred to pregnant women who underwent cesarean section at the same period. RESULTS: Of the 109,005 deliveries, twenty-seven women (0.25/1000-delivery) underwent cesarean hysterectomy. With multivariate analysis, the risk factors significantly associated with peripartum hysterectomy were placenta previa (adjusted OR = 67.96, 95% CI = 15.32, 301.46) and multiparity (adjusted OR = 7.30, 95% CI = 1.24, 43.19). When compared to controls, cases with cesarean hysterectomy had higher incidence of maternal and neonatal morbidities, needed more blood transfusion and required longer hospital stays. Operation performed in daytime found to have less mean blood loss (1,766 ml) compared to operation at nighttime (5,730 ml). CONCLUSIONS: Placenta previa and multiparity were significant risk factors of cesarean hysterectomy. Cesarean section in these cases should be done by experienced obstetricians with good preoperative care and if possible, during the daytime. Before an operation, each patient and her family should be counseled and informed regarding the risk for complications included hysterectomy. PMID- 17725147 TI - Risk factors of caesarean section due to cephalopelvic disproportion. AB - OBJECTIVE: To identify risk factors of cesarean section due to cephalopelvic disproportion SETTING: Department of Obstetrics and Gynecology, Faculty of Medicine, Siriraj Hospital. STUDY DESIGN: Case-control study. MATERIAL AND METHOD: One hundred and three singleton, viable, term pregnant women in cephalic presentation delivered by cesarean section due to cephalopelvic disproportion (CPD) and 105 controls gave normal birth just before or after the study case. Demographic, anthropometric data, labor characteristics, and neonatal outcomes were obtained from medical records. The expected risk indicators of the case and control groups were compared by using independent unpaired T-test and exact probability test as appropriate. Multiple logistic regression analysis was used to determine the significant risk factors (p < 0.05). RESULTS: Significant independent risk factors of cesarean section due to CPD were: estimated fetal weight (EFW) > 3,000 g (OR = 3.96, 95% CI = 2.06, 7.63), pre-pregnancy BMI > or = 25 kg/m2 (OR = 5.06, 95% CI = 1.67, 15.34), nulliparity (OR = 2.98, 95% CI = 1.31, 6.78) and the inadequacy of clinical pelvimetry (OR = 8.49, 95% CI = 1.01, 71.78), (p < 0.05). CONCLUSION: Risk factors for cesarean section due to CPD were EFW > 3,000 g, pre-pregnancy BMI > or = 25 kg/m2, nulliparity and the inadequacy of clinical pelvimetry. They are useful in the categorization of individual women into high and low CPD-risk groups. PMID- 17725148 TI - The changes of sexuality in Thai women during pregnancy. AB - OBJECTIVE: To determine the changes of sexuality during pregnancy in Thai women and to explore their attitudes and sources of information concerning sexuality during pregnancy. MATERIAL AND METHOD: Three hundred and sixty pregnant women who met the study criteria were recruited. Women at each trimester (n = 120) were interviewed with a structured questionnaire whether their sex desire, coital frequency and orgasmic rate decreased, increased or remained unchanged as compared with the prepregnancy period. The change in their favorite sexual position, concerns about sexual intercourse during pregnancy, and their sources of information regarding sexuality were also determined. RESULTS: The pregnant women at each trimester reported a gradual and significant decrease in sexual desire (p < 0.05) and coital frequency (p < 0.05). The change in orgasmic rate was not statistically significant (p = 0.06). Generally the preferred sexual position was "man on top" however, this gradually and significantly changed to "rear position " in each trimester of pregnancy (p < 0.05). Fifty nine percent of the women thought they could have sexual intercourse; however 79.7% of them were concerned about sexual intercourse during pregnancy. The main concern was the potential harm to the fetus. Sixty two percent of pregnant women received information about sexuality during pregnancy from their health physicians. CONCLUSION: Sexuality decreased significantly throughout pregnancy in Thai women. The majority of pregnant women are concerned about the adverse effects of sexual intercourse on pregnancy outcomes. Therefore, sexuality during pregnancy should be clearly counseled to all couples to reassure that sexual intercourse in normal pregnancy is safe. PMID- 17725150 TI - The location of needle insertion effect on maternal pain in amniocentesis. AB - OBJECTIVE: The purpose of this study was to determine whether maternal pain in amniocentesis was associated with the location of needle insertion and other identifiable clinical correlates. MATERIAL AND METHOD: This prospective study of mid-trimester amniocentesis was conducted between October 2005 and December 2005. Women were asked to complete a visual analog scale (VAS) after the amniocentesis. The distance from uterine fundus to symphysis pubis and from the location of needle insertion to symphysis pubis were measured and calculated to divide the insertion into two groups: upper third and middle third. The effect of previous amniocentesis, previous abdominal surgery, needle insertion through placenta and operators' experience was determined. The t-test was used for analysis; a probability value of < 0.05 was considered significant. RESULTS: Seventy-two women were participated in the study. The mean VAS was 2.7 +/- 2.1. The perception of pain was significantly less in patients with the upper-third insertion as compared with the middle third insertion (VAS 2.2 vs 3.9, p = 0.002). Previous amniocentesis, previous abdominal surgery, needle insertion through placenta and operators' experience had no impact on pain intensity. CONCLUSION: The pain from amniocentesis was significantly less in the patients with the needle insertion in the upper third of the uterus. PMID- 17725149 TI - The efficacy of ginger in prevention of postoperative nausea and vomiting after major gynecologic surgery. AB - OBJECTIVE: To study the efficacy of ginger in prevention of nausea and vomiting after major gynecologic surgery. STUDY DESIGN: Double blind randomized controlled trial. SETTING: Department of Obstetrics and Gynecology, Thammasat University Hospital, Faculty of Medicine, Thammasat University, Pathumthani, 12120, Thailand. MATERIAL AND METHOD: From March 2005 to April 2006, 120 patients who underwent major gynecologic surgery were randomized into group A (n = 60) and group B (n = 60). The patients in group A received two capsules of ginger taken one hour before the procedure (one capsule contains 0.5 gram of ginger powder). The patients in group B received the placebo. The visual analog nausea score (VANS) and frequency of vomiting were evaluated at 0, 2, 6, 12, and 24 hours after the operation. RESULTS: The results demonstrated the statistically significant differences in nausea between group A (48.3%) and group B (66.7%). The VANS was lower in group A compared to group B at 2, 6, 12, and 24 hours. The most statistically significant differences occurred at 2 and 6 hour. The incidence and frequency of vomiting in group A were lower than group B. Side effects caused by ginger were not detected. CONCLUSION: Ginger has efficacy in prevention of nausea and vomiting after major gynecologic surgery. PMID- 17725151 TI - The prevalence and causes of anemia during pregnancy in Maharaj Nakorn Chiang Mai Hospital. AB - OBJECTIVE: To determine the prevalence and causes of anemia during pregnancy in Maharaj Nakorn Chiang Mai Hospital. MATERIAL AND METHOD: The pregnant women were screened with hemoglobin, hematocrit, osmotic fragility test, hemoglobin E test and serology for hepatitis B, syphilis and HIV at first antenatal visit. In anemic cases, serum ferritin, serum iron/total iron binding capacity, or therapeutic trial with iron supplementation were performed to assess the iron status. The cases of abnormal thalassemia screening were followed by hemoglobin A2 level, PCR for alpha-1 (SEA type) and hemoglobin electrophoresis. Additional tests were stool exam, stool occult blood and red blood cell indices. Anemia was defined as a hemoglobin level less than 11.0 g/dl in the first and third trimester or less than 10.5 g/dl in the second trimester of pregnancy. The data was presented as mean, standard deviation and percentage. RESULTS: Six hundred and forty eight pregnant women were recruited. The prevalence of anemia was 20.1 percent (128 cases). Classified in each trimester the prevalence was 17.3%, 23.8% and 50.0% in the first, second and third trimester, respectively. Thalassemia carriers and diseases were detected in 56 from 102 anemic pregnant women (54.9%). Iron status was assessed in 58 cases and iron deficiency anemia was found in 25 cases (43.1%). Other causes of anemia were parasitic infection (8.7%) and anemia of chronic disease (2.7%). In 37 anemic pregnant women (33.0%), the causes of anemia were not found. CONCLUSION: The prevalence of anemia in pregnant women who first attended at the antenatal clinic was 20.1%. The main causes of anemia were thalassemia carriers/diseases and iron deficiency anemia. PMID- 17725152 TI - Transabdominal ultrasound in the assessment of postvoid residual urine volume in patients after hysterectomy. AB - OBJECTIVE: To evaluate the correlation between assessment of postvoid residual urine by transabdominal ultrasound and catheterization in patients after radical or transvaginal hysterectomy. MATERIAL AND METHOD: A cross-sectional study was conducted and 46 patients were enrolled after they had radical and transvaginal hysterectomy. After surgery, urinary catheter was indwelled. After catheter removal and the 3rd private voiding, the patients were sent for transabdominal ultrasound assessment of PVR at the Division of Maternal-Fetal Medicine. Complete drainage of bladder with standard catheterization was then performed and catheterized urine volume was recorded. PVR was calculated from previously published equation and compared with actual PVR from catheterization. RESULTS: Mean age of the patients was 55.9 years. The most common diagnoses were procidentia uteri (23.9%), Carcinoma of cervix stage 1b1 (23.9%), and prolapsed uteri grade 2 (21.7%). Radical hysterectomy with pelvic node dissection and vaginal hysterectomy with anterior colporhaphy and posterior colpoperiniorhaphy was performed each in 50% of cases. Mean duration of urinary catheter indwelling was 7.17 days for those underwent radical hysterectomy and 5 days for vaginal hysterectomy. The calculated PVR was significantly correlated with catheterized urine volume with correlation coefficient 0.93 (p < 0.001). If the usual cutoff of PVR > 100 ml was used to determine the necessity of re-indwelling catheter, among those with calculated PVR from ultrasound measurement < 100 ml, still 30% actually had actual PVR of > 100 ml. Among those with calculated PVR from ultrasound measurement >100 ml, all actually had actual PVR of > 100 ml. CONCLUSION: PVR estimation by ultrasound significantly correlated with actual PVR. This could reduce the process of repeat catheterization and give more comfort to the patients when the PVR is > 100 ml. PMID- 17725153 TI - Trends of perinatal deaths at Ramathibodi Hospital: 1995-2005. AB - OBJECTIVE: To study the trends in perinatal mortality rate and causes of perinatal deaths at Ramathibodi Hospital from 1995 to 2005. DESIGN: Retrospective descriptive study. MATERIAL AND METHOD: Review of medical records and reports during academic activities. RESULTS: The perinatal mortality rate was 5.10 per 1,000 births. Stillbirth and early neonatal death rate were 3.45 and 1.65 per 1,000 births, respectively. The most common cause of death was macerated fetus (46.80%). Causes of death from congenital anomalies, immaturity, asphyxia and specific conditions were 20.89%, 9.47%, 8.08% and 14.76%, respectively. CONCLUSION: The perinatal mortality rate at Ramathibodi Hospital has declined from 6.70 in 1985 to 5.10 per 1,000 births and remained steady for the last 11 years. Future progress in reducing perinatal deaths requires better understanding of the etiology of stillbirth to improve the strategies for prevention. PMID- 17725154 TI - Breastfeeding promotion in Thailand. AB - National Breastfeeding Project in Thailand began in 1989. The main activities were the promotion of the Baby-Friendly Hospital Initiative; legislation on maternity leave; and the Code of Marketing of Breastmilk Substitutes and related products. The development of Baby - Friendly Hospital Initiative may in part explain the increasing of prevalence rate of breastfeeding. However exclusive breastfeeding has not shown favorable increases. The survey in 2005 found exclusive breastfeeding at 6 months was 14.5% while the national target of the Ninth National Health Development Plan (NHDP) has been set at 30%. There are many factors affecting the success of breastfeeding promotion. The Ministry of Public Health, which is responsible for infant/child health, has to find solutions with the most potential for any problem related to such a matter especially prevention of childhood diseases. Furthermore, it must also create an environment where good health fundamentals for physical and intellectual developments from infancy to childhood and maturity exist. PMID- 17725155 TI - Role of molecular biology in obstetrics--modern single gene disorders diagnosis techniques. AB - Single gene mutations may lead to an inherited disorder with Mendelian inheritance patterns, of which over 8,000 disorders have been catalogued. The strategy of population screening, offering genetic counseling, prenatal diagnosis and termination of affected pregnancy has been successfully applied worldwide to reduce the number of new patients. Common fetal sampling techniques in utero include chorionic villous sampling, amniocentesis, and fetal blood sampling. Then appropriate analysis is applied for diagnosis, where karyotyping is mainly for chromosome abnormalities and PCR is for single gene disorders. Several modern molecular techniques are useful for identification of defects in single genes. Preimplantation genetic diagnosis is an advanced alternative giving the couple the chance to start a pregnancy ensuring that the baby is free from the genetic disease. It is the role of obstetricians to make most use of the advance molecular biology knowledge to have a healthy community. PMID- 17725156 TI - Gynecologic tumors during childhood and adolescence. AB - The majority of genital tumors are similar in almost all of the cell types but the frequency is different between children, adolescents, and female adults. The primary site of tumor is similar to the adults, however, the potential of malignant occurrence is higher among children and adolescents. The outline of this article covers clinical manifestation, differential diagnosis, investigation, and management in the particular disease/condition. The challenges of gynecology in children and adolescents are the complexity of physical and mental health, so the approach needs delicate skill and reasoning. Because they are not in full adulthood but in the transitional stage, the multidisciplinary and meticulous approach and management is a substantial issue. Balance and flexibility are the main key of this medical care. Extreme surgical intervention leading to over treatment or ignorance and carelessness leading to under quality of care are challenges facing the doctor. PMID- 17725157 TI - Verifying visual properties in sentence verification facilitates picture recognition memory. AB - According to the perceptual symbols theory (Barsalou, 1999), sensorimotor simulations underlie the representation of concepts. We investigated whether recognition memory for pictures of concepts was facilitated by earlier representation of visual properties of those concepts. During study, concept names (e.g., apple) were presented in a property verification task with a visual property (e.g., shiny) or with a nonvisual property (e.g., tart). Delayed picture recognition memory was better if the concept name had been presented with a visual property than if it had been presented with a nonvisual property. These results indicate that modality-specific simulations are used for concept representation. PMID- 17725158 TI - Basketball jump shooting is controlled online by vision. AB - An experiment was conducted to examine whether basketball jump shooting relies on online visual (i.e., dorsal stream-mediated) control rather than motor preprogramming. Seventeen expert basketball players (eight males and nine females) performed jump shots under normal vision and in three conditions in which movement initiation was delayed by zero, one, or two seconds relative to viewing the basket. Shots were evaluated in terms of both outcome and execution measures. Even though most shots still landed near the basket in the absence of vision, end-point accuracy was significantly better under normal visual conditions than under the delay conditions, where players tended to undershoot the basket. In addition, an overall decrease of inter-joint coordination strength and stability was found as a function of visual condition. Although these results do not exclude a role of motor preprogramming, they demonstrate that visual sensory information plays an important role in the continuous guidance of the basketball jump shot. PMID- 17725159 TI - Telling time from analog and digital clocks: a multiple-route account. AB - Does the naming of clocks always require conceptual preparation? To examine this question, speakers were presented with analog and digital clocks that had to be named in Dutch using either a relative (e.g., "quarter to four") or an absolute (e.g., "three forty-five") clock time expression format. Naming latencies showed evidence of conceptual preparation when speakers produced relative time expressions to analog and digital clocks, but not when they used absolute time expressions. These findings indicate that conceptual mediation is not always mandatory for telling time, but instead depends on clock time expression format, supporting a multiple-route account of Dutch clock time naming. PMID- 17725160 TI - A bottleneck in face identification: repetition priming from flanker images. AB - There is evidence that face processing is capacity-limited in distractor interference tasks and in tasks requiring overt recognition memory. We examined whether capacity limits for faces can be observed with a more sensitive measure of visual processing, by measuring repetition priming of flanker faces that were presented alongside a face or a nonface target. In Experiment 1, we found identity priming for face flankers, by measuring repetition priming across a change in image, during task-relevant nonface processing, but not during the processing of a concurrently-presented face target. Experiment 2 showed perceptual priming of the flanker faces, across identical images at prime and test, when they were presented alongside a face target. In a third Experiment, all of these effects were replicated by measuring identity priming and perceptual priming within the same task. Overall, these results imply that face processing is capacity limited, such that only a single face can be identified at one time. Merely attending to a target face appears sufficient to trigger these capacity limits, thereby extinguishing identification of a second face in the display, although our results demonstrate that the additional face remains at least subject to superficial image processing. PMID- 17725161 TI - The size of the Simon effect depends on the nature of the relevant task. AB - Four experiments were conducted to investigate contextual modulations of the Simon effect. The results showed that the Simon effect was quantitatively different depending on which kind of task needed to be performed. Importantly, this effect did not depend on the relative processing time of the relevant dimension, nor on a direct or indirect overlap between the relevant and irrelevant stimulus part. To account for the data, we refer to the neural overlap hypothesis, which extends the definition of dimensional overlap (Kornblum, Hasbroucq, & Osman, 1990) with similarity of processing regions as the key factor for the interaction between relevant and irrelevant information processing. PMID- 17725162 TI - Reading aloud: when the effect of stimulus quality distinguishes between cascaded and thresholded components. AB - A central feature of many formal accounts of reading aloud, and of Coltheart and colleagues dual-route cascaded model in particular, is that activation across various modules is cascaded. Evidence is reviewed that this assumption is problematic in a particular context, along with a solution that involves thresholding the output of the letter level to the nonlexical routine. Consideration of the known effects of repetition leads to the prediction of a three-way interaction between stimulus quality, repetition, and lexicality in which repetition and stimulus quality interact when reading aloud exception words, but produce additive effects when reading aloud nonwords. The result of such an experiment confirms this prediction, and appears consistent with the localized dual-route model. Implications for other accounts are briefly noted. PMID- 17725163 TI - Masked priming effects in semantic categorization are independent of category size. AB - The question whether subliminal primes can activate their semantic meaning or not is still of interest today. Three different competing theories have tried to account for the often inconsistent research results: The semantic categorization hypothesis, the direct motor specification hypothesis, and the category search model. The present study aimed to shed light on these different points of view by examining the role of category size in response congruency effects when novel primes are used. Three experiments were conducted and a transparent pattern of results emerged: Significant priming effects were obtained across different tasks, irrespective of category size and irrespective of stimulus set size. The findings are discussed in terms of the three theoretical frameworks. It becomes clear that the present results provide strong evidence in favor of the semantic categorization hypothesis, which assumes semantic processing of subliminal primes. PMID- 17725164 TI - Are primary-school-aged children experts in spatial associate learning? AB - In two experiments (Experiment 1: N = 180, Experiment 2: N = 150), we investigated the anecdotal observation that school age children are assumed to be experts in spatial associate learning. In the first experiment, second graders, sixth graders, and adults learned the associations between 32 pictures and either a position or a word. 16 pictures had each to be associated with one position in a 4-by-4 grid of squares (spatial condition); the other 16 pictures had each to be associated to one of 16 monosyllabic words (verbal condition). After a 3 min distractor interval the associated position or word had to be retrieved with the pictures as cues. In Experiment 2, the results were replicated in principle with modifications in the experimental details. Performance improvement as a function of age turned out to be substantially larger in the verbal condition compared to the spatial one. The results are traced back to the idea that spatial associate learning is a cognitive function maturating early during life span. PMID- 17725165 TI - [Unifocal eosinophilic granuloma of the temporal bone]. AB - We present a case of a twelve year old child with a eosinophilic granuloma of the temporal bone. The eosinophilic granuloma is the most frecuent and most benign form of the histiocytosis of the Langerhans cells. The frecuency of the othological manifestations of this condition varies between 15-60 percent and radiologically, the images are characterized by litho-lesions with sharp edges. The diagnosis is histological and the treatment includes surgical intervention accompanied by inter-lesion corticoid-therapy and/or radiotherapy. PMID- 17725167 TI - [Simultaneous pulmonar, laryngeal and lingual affectation by Mycobacterium tuberculosis]. AB - The incidence of tuberculosis has lately increased in developed countries. The most frequent affectation is the pulmonar one and in the ORL area the laryngeal. The lingual affectation is exceptional. We present a case of a man 39 years old, with bilateral pulmonar, left vocal cord and mobile tongue affectation, negative Mantoux, positive spit culture and presence of acido-alcohol resistent bacillus in lingual and laryngeal biopsies. After antituberculosis treatment during 6 months the laryngeal and lingual lesions disappeared. We have only found two cases published of simultaneous tuberculosis in these three localisations in the last 30 years. PMID- 17725166 TI - [Metastasis in maxilar sinus as only manifestation of disseminate renal adenocarcinoma]. AB - Paranasal sinuses and nose metastasis are very uncommon. About 50 have been reported. Renal cell carcinoma is the primary neoplasm which most frequently metastasizes in the nasosinusal region, followed by breast and lug. Symptoms are unspecific, but the epistaxis constitutes the most common sign due to the significant vascularizations of the tumor. Prognosis is poor. The survival rate fluctuates between 15-30% at 5 years. Surgery is the elective treatment. PMID- 17725168 TI - [Nasal neurinoma: communication of a case and clinicopathologic analysis]. AB - The schwannomas are tumors arising from nervous tissue. It appears very rarely in the nose and paranasal sinuses. We report a case of a female whit nasal obstruction that presents a nasal neurinoma schwannoma. PMID- 17725169 TI - [Kartagener sindrome (primary ciliary dyskinesia). Report of a case and literature review]. AB - Kartagener syndrome (a clinical variant of primary ciliary dyskinesia) is a recessive autossomical disease characterized by the triad of chronic sinusitis, bronchiectasis and situs inversus with dextrocardia. We report one case described in a 8 years old boy who besides presented a seromucous otitis and bronchitis of repetition. Finally we performed a short bibliographic review at respect of this uncommon pathology. PMID- 17725171 TI - [Malignant mucous primary sinonasal melanoma. A clinic case]. AB - The melanomas are unusual tumours with a high mortality. The mucosal malignant melanoma type supposes loss than 1% of the total of melanoma. The initial symptoms are unspecific and the regional metastasis are rare. The surgical approach it's the most effective treatment complemented with radiotherapy and or chimiotherapy. We present the case of primary nasal mucosal malignant melanoma and review the litterature of this disease. PMID- 17725172 TI - [Vogt Koyanagi Harada syndrome. Report of a case with hearing loss, tinnitus, vertigo associated to uveitis]. AB - Vogt-Koyanagi-Harada sindrome is an autoimmune sistemic disease characterized by granulomatous bilateral uveitis with involvement of the central nervous system which can compromise the VIII craneal pair function producing tinnitus and neurosensorial hypoacusia. We report a case diagnosed in a young woman who also suffered episodes of vertigo. We review the literature of that pathology. PMID- 17725170 TI - [Our experience in the treatment of the tumors of parotid gland]. AB - We analyse our results in the treatment of the tumors of the parotid gland, diagnosticated from 1981 till end of 2004. We saw 132 patients with tumors of the parotid, being 41 of them malignant. The surgical technique more used was the total parotidectomy with conservation of the facial nerve. The global survival obtained in the malignant tumors was 60% after five years. Surgery is the treatment of election in the tumors of epitelial origin of the parotid gland. The derived of the lymphoid tissue must be treated by other ways and are inheritance of the hematologic oncology. PMID- 17725173 TI - [Tinnitus of vascular type. Diagnostic possibilities]. AB - It's defined tinnitus as an auditive perception of internal origin that it does not answer to vibratory external action. The rest of the sounds are considered as real biological noises and not properly as tinnitus. Tinnitus is a very common symptom in our practice. It is important to determine what causes it, since medical treatment is effective in some cases and prevents serious complications, severe bleeding and neurological consequence if any surgical treatment is carried out. We present two cases of tinnitus of vascular origen, the first caused by venous malformation and the second by an arterial one. We review the literature of this entity. PMID- 17725174 TI - [Peripheral vertiginous syndrome with osteocervical lytic pathology. Importance of the exploration and its differential diagnosis]. AB - We are reporting the case of a 52 years old male with a peripheral vertiginous syndrome which could have been diagnosed as a benign paroxysmal positional vertigo. In a craneocervical CT appeared an osteolytical lesion on C3 vertebral body. With this article we pretend to emphasize the importance of a complete exploration and the differential diagnosis in the peripheral vertiginous pathology. PMID- 17725175 TI - Insertion/deletion polymorphism in the promoter of NFKB1 as a potential molecular marker for the risk of recurrence in superficial bladder cancer. AB - OBJECTIVE: Bladder cancer is a leading cause of morbidity and mortality. Despite intensive research efforts, histopathological diagnosis of grade and stage, the most important markers for predicting the outcome of the disease, is still necessary. Therefore, a new candidate gene was investigated with regard to its potential utility as a prognostic marker for the course of disease in bladder cancer. A functional insertion/deletion polymorphism has recently been identified in the promoter region of NFKB1 which regulates transcription of the transcription factor NF-kappaB. Several genes involved in oncogenic processes are controlled by NF-kappaB and might be influenced by alterations in its expression. MATERIAL AND METHODS: Genotype distributions in patients with bladder cancer (n = 242), in a subgroup consisting only of patients with superficial bladder cancer (n = 101, stage pTa and pT1) and in a group of healthy control subjects (n = 307) were determined using pyrosequencing. The results were compared and the relationship between genotype and survival, and genotype and first recurrence were determined. NFKB1 expression was assessed using native tumor tissue and quantitative real-time PCR. RESULTS: No statistically significant differences in genotype frequency between healthy controls and patients were detected. Survival was not dependent on the genotype of the polymorphism. Nevertheless, time to first recurrence differed significantly between genotypes (p = 0.037) and this difference could be ascribed to the patients with superficial tumors (p = 0.013). Moreover, multivariate analysis showed that this promoter variant was an independent risk factor. The risk of recurrence in patients with superficial tumors and the homozygous deletion was higher (HR 2.86, p = 0.005) than in those with the homozygous insertion. NFKB1 mRNA expression was highest in tumors from patients carrying the homozygous insertion genotype (p = 0.038). CONCLUSION: These results suggest that the NFKB1 promoter polymorphism is a useful marker for the identification of patients with superficial bladder cancer where the risk of recurrence is high. PMID- 17725176 TI - Reduction in non-glomerular renal clearance of the caffeine metabolite 1 methylxanthine by probenecid. AB - OBJECTIVE: Urinary caffeine metabolic ratios used to quantify the activity of numerous drug-metabolizing enzymes are an established component of cocktail approaches for metabolic phenotyping. Because in vitro evidence suggests that 1 methylxanthine (1-MX), a major caffeine metabolite, is actively secreted into urine by organic anion transporters (hOATs), coadministration of renal hOAT inhibitors like probenecid may impair these procedures. METHODS: In a randomized, placebo-controlled, double-blind crossover design, single oral doses of 300 mg caffeine with oral coadministration of placebo or 500 mg probenecid 3 times daily for 2 days were administered to 7 healthy men. The plasma and urine concentrations of caffeine and its major metabolites 1,7-dimethylxanthine (1,7 DMX) and 1-MX were determined by high-performance liquid chromatography. RESULTS: Coadministration of probenecid resulted in a 34% reduction of the renal clearance of 1-MX (mean +/- SD 190 +/- 42 versus 290 +/- 83 ml min(-1), 95% CI on difference 0.2, 200, p = 0.04) with a 41% reduction in its estimated non glomerular clearance. The renal clearances of caffeine and 1,7-DMX and the area under the plasma concentration-time curves of all substances were not significantly changed. CONCLUSIONS: 1-MX undergoes renal tubular secretion which is substantially reduced by probenecid, possibly due to inhibition of renal hOATs. This inhibition may explain the influence of probenecid on urinary caffeine metabolic ratios and, thus, its impact on the assessment of enzyme activities. It also suggests that 1-MX might serve as a model substrate for the renal tubular transport of organic anions. PMID- 17725177 TI - Modeling the influence of non-adherence on antibiotic efficacy: application to ciprofloxacin. AB - OBJECTIVE: To evaluate the consequences for antibiotic efficacy of different types of poor adherence to a short-term dosing regimen. Ciprofloxacin was taken as an example. METHOD: A simulation study on a 2-compartment pharmacokinetic model and parameter estimates taken from the literature was performed. Two empirical efficacy measures as well as a specific pharmacodynamic model of the bacterial kill curve were used. Four patterns of non-adherence were investigated: dosage omission, irregular dosing intervals, delayed dosing and treatment discontinuation. RESULTS: Errors in timing of doses with a standard deviation less than 2 h had a minor effect on antibiotic efficacy. Dosage omission, in contrast, has a significant influence on the antibacterial effect of ciprofloxacin. CONCLUSIONS: non-adherence patterns are difficult to measure experimentally, thus, recommended dosing regimens should be sufficiently robust against most of the nonintentional disturbances. PMID- 17725178 TI - Plasma and urine pharmacokinetics of niacin and its metabolites from an extended release niacin formulation. AB - OBJECTIVE: To characterize plasma and urine pharmacokinetics of niacin and its metabolites after oral administration of 2,000 mg of extended-release (ER) niacin in healthy male volunteers. METHODS: Niacin ER was administered to 12 healthy male subjects following a low-fat snack. Plasma was collected for 12 h post dose and was analyzed for niacin, nicotinuric acid (NUA), nicotinamide (NAM) and nicotinamide-N-oxide (NNO). Urine was collected for 96 h post dose and analyzed for niacin and its metabolites, NUA, NAM, NNO, N-methylnicotinamide (MNA) and N methyl-2-pyridone-5-carboxamide (2PY). RESULTS: Mean niacin Cmax and AUC(0-t) values were 9.3 microg/ml and 26.2 microg x h/ml and were the highest of all analytes measured. Peak niacin and NUA levels occurred at 4.6 h (median) while tmax for NAM and NNO were 8.6 and 11.1 h, respectively. The mean plasma terminal half-life for niacin (0.9 h) and NUA (1.3 h) was shorter as compared to NAM (4.3 h). Urine recovery of niacin and metabolites accounted for 69.5% of the administered dose; only 3.2% was excreted as niacin. The highest recovery was for 2PY (37.9%), followed by MNA (16.0%) and NUA (11.6%). Mean half-lives for 2PY and MNA calculated in urine were 12.6 and 12.8 h, respectively. CONCLUSIONS: Niacin was extensively metabolized following oral administration, and about 70% of the administered dose is recovered in urine in 96 h as niacin, NUA, MNA, NNO, NAM and 2PY. The plasma levels of the parent niacin were higher than its metabolites though only about 3% of the unchanged drug is recovered in urine. PMID- 17725179 TI - Cost of Type 2 Diabetes mellitus in Hong Kong Chinese. AB - OBJECTIVE: Hong Kong (HK) is a special administrative region of China as well as being a metropolitan city. In HK, like in many developed countries, Diabetes mellitus, with over 97% of diabetic patients having Type 2 Diabetes mellitus (Type 2 DM), is a growing public health problem but the local financial burden has never been investigated. The primary objectives of this study were to evaluate from the social perspective the costs of Type 2 DM, to identify the major cost drivers, and the proportion of the burden shared by the government, patient and the society. The study was carried out in a group of Hong Kong Chinese patients attending a government hospital. The economic impact of Type 2 DM on local and governmental healthcare expenditure was also examined. METHODS: A retrospective cohort observational study was conducted in Type 2 DM patients attending the Diabetes Mellitus Outpatient Clinic at a public hospital in the period January 2004 to May 2004, in which 204 patients were randomly selected and invited to join this study. A total of 147 patients were subsequently enrolled giving an inclusion rate of 72%. RESULTS: Annual total cost of Type 2 DM in a patient was US$ 1,725 +/- 2,044 (HK$ 13,457 +/- 15,943) with direct costs accounting for > 87.9%. The government was the major payer with over 78.4% of the total costs. Annual total direct medical costs per patient were US$ 1,492 +/- 1,716 (HK$ 11,638 +/- 13,386) of which the government paid 90.6%. Direct medical costs increased markedly if complications were present. In patients with microvascular or macrovascular complications only, the costs increased 1.1-fold compared to those for patients without complications. If both microvascular and macrovascular complications were present in the same patient, the costs were 1.3 fold higher than in patients without complications. CONCLUSION: Costs of Type 2 DM have a significant impact on the local healthcare budget. It contributed in 2004 up to 3.9% of the total HK healthcare expenditure and 6.4% of the HK Hospital Authority's (public sector) expenditures on health. PMID- 17725180 TI - Comparative bioavailability/bioequivalence of two different stavudine 40 mg capsule formulations: a randomized, 2-way, crossover study in healthy volunteers under fasting condition. AB - PURPOSE: The aim of this study was to compare the single-dose oral bioavailability of two formulations of stavudine 40 mg capsules in healthy human subjects. METHODS: A bioequivalence study of two oral capsule formulations of 40 mg stavudine was carried out in 40 healthy volunteers following a single-dose, 2 sequence, crossover and randomized design. The two formulations were stavudine 40 mg capsules (Ranbaxy Laboratories Ltd., Haryana, India) as test and zerit 40 mg capsules (Bristol-Myers Squibb, Princeton, NJ, USA) as reference product. Test and reference capsules were administered to each subject in each period separated by a 3-day washout period. Serial blood samples were collected for a period of 10 h. Blood plasma was analyzed for stavudine using a sensitive, reproducible, accurate and validated LC-MS/MS method. Pharmacokinetic parameters, including AUC(0-t), AUC(0-inf), C(max), t(max), t(1/2) and lambda(z), were determined from plasma concentrations for both formulations. AUC(0-t), AUC(0-inf) and C(max) were tested for bioequivalence after log-transformation of data. RESULTS: The LC-MS/MS method, used to quantify stavudine in human plasma, was specific and sensitive for stavudine. Plasma concentration profiles of stavudine test and reference treatments were similar. Geometric mean ratios and 90% confidence intervals for C(max), AUC(0-t) and AUC(0-inf) for stavudine were 99.9 (93.9-106), 99.9 (98.4 101) and 99.8 (98.2-101), respectively. Untransformed results for the same parameters were consistent with the natural log-transformed data. CONCLUSION: The two stavudine 40 mg capsule formulations examined were bioequivalent and may be used interchangeably in medical practice. PMID- 17725181 TI - Frequency of UDP-glucuronosyltransferase 1 (UGT1A1) gene promoter polymorphisms in neonates with prolonged and pathological jaundice in the Denizli region of Turkey. PMID- 17725182 TI - [Assessment methods and preventive measures focusing on relationships]. AB - In this contribution relationship-oriented assessment methods and preventive measures during infancy and childhood are founded in an ecological and differential understanding of development in context. Using selected developmental milestones it is demonstrated that relationships as a social context play an important role particularly during early infancy. Criteria for describing well functioning and maladaptive relationships can be derived from theoretical presumptions, empirical longitudinal studies and health related clinical judgements. These criteria may serve as guidelines for interventions, especially in cases of children with a clinical diagnosis of child neglect. Possible procedures to assess the quality of relationships are discussed using methods from contributions in this issue of the journal as examples. Diagnostic and preventive procedures are seen as mutually interacting within continuous feedback loops, where assessment procedures serve to both give evidence for the efficacy of interventions and for specifying further preventive methods. PMID- 17725184 TI - [Is it possible to assess attachment in children between three and six years using a questionnaire?]. AB - So far the measurement of attachment of three to six year old children is only possible using time consuming behaviour observation or semiprojective play procedures. The aim of this work was to develop a more easily manageable questionnaire for practitioners to assess attachment in kindergarten children and to validate it by already existing more time-consuming attachment measures. Kindergarten entry was chosen as a natural stress inducing and thus attachment behaviour provoking situation using the professional caregivers in kindergarten as observers. To validate the questionnaire a sample of 118 kindergarten children were recruited. Cluster analysis revealed three groups comparable to secure, avoidant and ambivalent attachment classifications but failed to identify a disorganized attachment group. Comparisons with other attachment measures (reunion in kindergarten, the Strange Situation for Preschool Children and the Attachment Story Completion Task) revealed only partially significant concordances. With regard to additionally assessed domains of social-emotional and cognitive development the expected coherences where found for behaviour problems, cognitive development and problems during kindergarten entry but not for self concept. Over all it was not possible to assess attachment using the questionnaire. Explanations are discussed and the results are compared to other research findings. PMID- 17725183 TI - [Risk assessment of neglect and maltreatment in infants and toddlers. Chances of early preventive intervention]. AB - The German child protection system lacks of interdisciplinary and standardized procedures for screening and diagnosing child maltreatment as well as for service delivery. Evidence based assessments of risk-screening in combination with consensus-based models for risk-judgement seem to predict the best possible results. A central part of determining whether an infant is at risk is to evaluate various domains of parental competencies and skills. In particular assessment procedures based on attachment research have proven to be practically and methodologically relevant. These include interactive and video-based observational methods as well as parental representations as sources of information for risk assessment. Attachment based intervention and treatment programs are effective, especially with regard to enhancing paternal sensitive behavior. However, these programs need to be adapted to delivery for specific risk groups. Overall an interdisciplinary approach with regard to the programs as well as to the training of the professionals has to be taken into account. PMID- 17725185 TI - [Attachment behavior with respect to mothers and fathers and attachment representations in five and seven-year-old children]. AB - During preschool and early school age attachment quality can be assessed by different means: at the behavioral level by the Strange Situation (SS), at the representational level by semiprojective methods using story stems or pictures. Both methods gain access to different levels of a theoretically assumed inner working model of attachment, in which attachment at the behavioral level is supposed to be person specific, attachment at the representational level generalized. This study aimed at analyzing whether attachment behavior to mother and father is associated, and how it is linked to the generalized attachment representation. It was also examined whether in the case of no association between mother and father attachment behavior towards the major attachment figure is linked to the attachment representation. In the Duesseldorf study 67 children aged 5 years were observed in the SS with mother, 31 of them also in the SS with father. At the age of 6.5 years an attachment story completion task was conducted. When person specific attachment to mother and father was congruent (SS secure n=6, or insecure n=8) the attachment representation was consistent as well, when father and mother attachment were discrepant no association with attachment representation could be found. The findings did not confirm a stronger influence of the major attachment figure on the formation of the attachment representation. PMID- 17725186 TI - ["I keep cool": Relationship oriented training of prosocial behaviour and constructive conflict solving for elementary school children]. AB - The evaluation of a preventive training with first graders is reported ("I keep cool"). The training focuses on the prevention of aggressive behaviour and of destructive problem solving by means of teaching prosocial behaviour and constructive problem solving. From a sample of 143 children, 92 participated in the training, 51 served as controls. Children's social competencies and behaviour problems were assessed before, after, and four months after the training via interviews with children, teachers' ratings, and separate ratings of mothers and fathers. After the training, children reported more constructive problem solving, more prosocial behavior, and a higher level of impulse control. Girls showed a lowered level of destructive problem solving behavior immediately after the training, and a lowered level of stress when confronted with intermarital conflicts of their parents at the follow-up assessment. Teachers reported less internalizing and shyness in both sexes at the follow-up assessment. Mothers reported a marginally significant lower level of oppositional-aggressive behaviour in boys immediately after the training, fathers reported a significant lower level of oppositional-aggressive behaviour and of internalizing and shyness in children of both sexes. The effect sizes of .23 < d < .94 are satisfying and comparable with those of similar programmes. PMID- 17725187 TI - [The added value of therapy]. PMID- 17725188 TI - [New therapeutic guidelines in cardiology]. AB - Cardiovascular diseases are the leading cause of mortality in the so-called industrial countries. An appropriate management is mandatory and its modalities should be known and applied by physicians. European and American recommendations are regularly published and updated. They are available on the web sites of the European Society of Cardiology (www.escardio.org), the American Heart Association (www.aha.org) and the American College of Cardiology (www.acc.org This article describes the recent therapeutic options of some cardiovascular diseases, especially coronary artery disease, valvular diseases, atrial fibrillation and implantable defibrillator, but is far to be exhaustive. PMID- 17725189 TI - [Evidence for avoiding the use of beta-blockers as first line therapy in hypertension]. AB - Arterial hypertension is a significant risk factor for cardiovascular disease, proportional to the blood pressure level. Treating hypertension reduces the risk. Until recently, beta-blockers were considered as a first line class for hypertension management. The British Hypertension Society has recently pronounced that using beta-blockers as first line antihypertensive therapy is no good choice since these agents are less protective than other antihypertensive classes against cardiovascular disorders and diabetes mellitus, especially when used in association with diuretics. PMID- 17725190 TI - [New therapeutic guidelines in lower limb arteriopathy]. AB - This article describes the recent therapeutic options for lower limb arteriopathy and, as much as possible, analyzes the medical and surgical treatments according to the recommendations and levels of evidence. PMID- 17725191 TI - [Recent advances in cardiac and vascular surgery]. AB - Significant advances in cardiac surgery include hypothermic circulatory arrest for complex aortic surgery, stentless valve for aortic valvulopathies, conservative treatment of the insufficient aortic valve, surgical interruption of the electrical circuits involved in atrial fibrillation and new extra-corporeal circuits (SMA) to decrease inflammatory systemic reactions, and for, the same reason, heart beating coronary surgery. Advances in vascular surgery include aortic endoprosthesis, coeliscopic aortic surgery and less invasive superficial veins surgery. PMID- 17725192 TI - [New developments in anesthesia-reanimation for ambulatory procedures]. AB - The one day clinic possesses its own structure and organisation; patient management is also specific. Preoperative visit and assessment are programmed at least 48 hours before anesthesia. Preoperative examinations and choice of anesthetic technique (sedation associated with local anesthesia or not, general anesthesia, locoregional anesthesia, or hypnosedation) are discussed and determined depending upon medical history, clinical examination, and type of procedure. General recommandations, instructions about fasting, interruption of some therapies, and introduction of new medication(s) are explained orally and also provided in a written document. New anesthetics and analgesics allow quick awakening and recovery of vital functions, and subsequently rapid hospital discharge. Prevention and aggressive treatment of postoperative nausea and vomiting are also a major concern in our anesthesic management of ambulatory patient. PMID- 17725193 TI - [What's new in intensive care medicine?]. AB - Over the last ten years, much progress has been achieved in intensive care medicine. Large randomized studies, most often their multicentric, were performed and their results were translated into rules to be followed for the most appropriate treatment of life-threatening organ failures. The place of non invasive ventilation in the management of hypercapnic or hypoxic respiratory insufficiencies was thus defined, and the methods for less traumatic mechanical ventilation were specified. The techniques of renal replacement therapy were compared and the optimal doses of dialysis or hemofiltration were established. The metabolic support of the patients was also altered following landmark studies, such as the management of blood glucose, which deeply influenced the approach to critically ill patients. PMID- 17725194 TI - [Recent therapeutic advances in intensive care: update on severe sepsis/septic shock and on pulmonary embolism]. AB - Septic shock and pulmonary embolism remain leading causes of death in intensive care units. Recent therapeutic advances have contributed to decrease the mortality rate of septic shock. Among these, early goal directed hemodynamic therapy, corticoid and activated protein C are the most efficient. However, due to the increased incidence of sepsis, the absolute number of deaths remains unacceptably high. In order to improve the prognosis of septic patients, the "surviving sepsis campaign" started in 2002. Its main objective is to decrease mortality rate of sepsis by 25% in the next five years. The diagnostic strategy of pulmonary embolism has been improved by the use of validated algorithms using clinical probability, d-dimers, angioscan and venous doppler. The growing use of low molecular weight heparin has also improved and facilitated the therapeutic management of pulmonary embolism while indication of fibrinolysis in presence of right ventricular dysfunction, but without shock, remains controversial. PMID- 17725195 TI - [Update in the management of persistent pulmonary hypertension of the newborn]. AB - Persistent pulmonary hypertension of the newborn is a severe disease leading to persistent and refractory hypoxemia with bad outcomes. The introduction of inhaled nitric oxide therapy significantly improved short and long term prognosis of those infants. More recently, sildenafil also appeared promising, but regimen and indications still need to be delineated. PMID- 17725196 TI - [Therapeutic update in respiratory medicine]. AB - We review what we think to be the major advances in the field of respiratory medicine over the last ten years. We concentrate here on four major diseases i.e. asthma, chronic obstructive pulmonary disease (COPD), lung cancer and chronic respiratory insufficiency due to restrictive disorders. Therapeutic advances are based either on new drugs or on new disease management concepts and, in some cases, on new medical devices. These advances have allowed a reduction in mortality and morbidity in aforementioned diseases. PMID- 17725197 TI - [Management of acute bronchiolitis in newborns]. AB - Acute bronchiolitis is a common condition of viral origin with attention of treating hypoxia and maintaining hydration. Medications are often ineffective, although widely used in our countries. If the spontaneous cure is the rule, the persistence of a respiratory symptomatology (cough or wheezing) during several weeks is not exceptional. PMID- 17725198 TI - [Respiratory syncytial immunoprophylaxis with palivizumab]. AB - Respiratory syncytial virus (RSV) is a serious pathogen causing significant morbidity, especially in premature infants and infants with chronic lung disease or significant congenital heart disease. There is no specific treatment for RSV infection and the therapy is essentially supportive. Therefore, prophylaxis is the best strategy against RSV disease. Passive immunization with monoclonal antibodies (palivizumab) provides protection against severe RSV infection and significantly reduces hospitalizations in high-risk childrens. However, palizumab is an expensive drug and its use should be reserved for children at the highest risk of severe RSV disease. PMID- 17725199 TI - [Therapeutic update in gastroenterology]. AB - During the last decade, advances in molecular biology and biotechnology allowed, the development of biological treatments aimed at more precise targets. New algorithms in inflammatory bowel diseases, chronic hepatitis C and digestive oncology are examples of the marked progress achieved by these therapies. PMID- 17725200 TI - [Recent advances in liver surgery and transplantation]. AB - Over the last 20 years, significant improvements in hepatic surgery and transplantation have allowed better results. Better patients selection, new preoperative modalities aiming at modifying the volume of the liver or the tumour, new surgical techniques, and better postoperative management are the keys to improved outcome. These progresses are reviewed in this article. In hepatic surgery, the latest surgical improvements are the possibility of laparoscopic hepatic resection and of radiofrequency ablation. Modern neoadjuvant chemotherapy may in some cases allow a reduction of large liver colorectal metastases and render them resectable. Improved radiological techniques allow better planning of the surgical resections, reduction of the risks by calculation of the residual liver mass, and induction of liver hypertrophy by preoperative portal embolisation. In liver transplantation, the most significant changes were the use of living related liver donors and of non-heart beating donors to overcome the cadaveric organ donor shortage. PMID- 17725201 TI - [Recent advances in the management of diabetes mellitus]. AB - The recent epidemic of type 2 diabetes and the recognition that achieving specific glycemic goals can reduce morbidity have made the effective treatment of hyperglycemia a priority. The new therapeutic agents and the development of algorithms for the adjustment of therapy might contribute to an improved management of the disease. Moreover, type 2 diabetes is frequently associated with other co-morbidities (obesity, hypertension, dyslipidaemia, prothrombotic state). The appropriate management of patients with type 2 diabetes requires a global approach targeting each risk factor in order to reduce cardiovascular morbidity and mortality. This challenge represents a major public health issue. In type 1 diabetes patients, intensive therapy such as in the Diabetes Control and Complications Trial (DCCT) has been shown to obtain long-term beneficial effects on the reduction of the risk of progressive retinopathy, neuropathy and nephropathy and of the risk of cardiovascular disease. This benefit reinforces the original DCCT message that intensive therapy should be implemented as early as possible in people with type 1 diabetes. The recent development of new insulin analogues and the technical improvements of portable insulin pumps might contribute to obtain such a better metabolic control. PMID- 17725202 TI - [Recent treatment perspectives in lipidology]. AB - Clinical lipidology has gained its recognition with the publication of numerous clinical trials since the 4S study in 1994. Since that time statins have fully confirmed their promises and play now a crucial role in the battle against cardiovascular diseases. The last decade has been dominated by two demonstrations that apparently are discordant: (1) the lower the cholesterol level with the pharmacological intervention, the lower the risk of cardiovascular complications, arguing for the use of very efficacious cholesterol-lowering therapies; and (2) the cardiovascular protection provided by statins is present whatever the baseline cholesterol level, supporting the concept of pleiotropic effects of statins. As a consequence, statin treatment should be prescribed and intensified according to the high individual cardiovascular risk rather than because of the cholesterol level stricto sensu. Statin therapy should be completed by the addition of ezetimibe when LDL cholesterol level remains above target values or by the addition of fenofibrate when triglyceride levels are high and/or HDL cholesterol level is low. New pharmacological approaches aiming at further improving lipid profile, especially by targeting low HDL cholesterol levels, are currently in clinical development. PMID- 17725203 TI - [Recent advances in the management of obesity]. AB - The management of an obese patient aims not only at obtaining a durable weight loss, but also at attenuating various associated risk factors. This latter objective may already be obtained with a rather moderate weight reduction (5-10% of initial body weight). The first step should favour life-style changes (diet and physical exercise), eventually together with a psychological support. In case of insufficient success, a pharmacological approach may be considered, in addition to life-style advices. Pharmacotherapy currently includes drugs that act on the central nervous system to decrease appetite (sibutramine), in the gastrointestinal tract to diminish fat absorption (orlistat) or at both central and peripheral sites (rimonabant). In case of extreme obesity or severe obesity associated with comorbidities, refractory to medical approaches, bariatric surgery may represent the only solution to obtain a major and sustained weight loss, together with a significant improvement of associated risk factors. Gastroplasty, especially laparoscopic gastric banding, has become very popular in our country. However, because of several limitations, it is increasingly replaced by derivative procedures, especially gastric bypass. In all cases, a multidisciplinary, integrated and individualized approach should be recommended, using realistic goals and targeting long-term weight reduction and improved health. PMID- 17725204 TI - [What's new in orthopaedic surgery: hopes and facts in total hip and spine arthroplasty]. AB - Progress in implant design and surface properties have improved long-term survival of total hip prosthesis and lowered the incidence of dislocation. New materials, particularly ceramics and metals, decrease the risk for implant loosening because they induce less particle disease than polyethylene debris. These new materials have been submitted to simulator studies before being released for clinical use. They have been used since a sufficient amount of time in clinical practice to consider them as being part of our current armamentarium. They enable the orthopaedic surgeon to tailor the optimal hip prosthesis to each patient's need, depending on his/her bone stock, activity level and life expectancy. Disk prostheses and the general concept of non fusion surgery in spine surgery seems attractive, since intervertebral fusion carries a number of drawbacks, particularly at the level of adjacent segments. However, the documented follow-up of non-fusion spine surgery is at present insufficient to consider a widespread use of these new technologies. Their own possible complications are largely unknown and they do not replace bone fusion in the most clear-cut accepted indications for spine surgery. The use of disk prostheses should therefore be strictly limited according to present knowledge. PMID- 17725205 TI - [Update in non-union treatment]. AB - Non-union of long bones is still a dreadfull complication. Depending on the type and location of the non-union, we describe current treatment options including various types of bone fixation, isolated or vascularised bone grafts, biophysical enhancement and newer developments with biological bone inducers (BMP). PMID- 17725206 TI - [Advances in the treatment of postmenopausal osteoporosis]. AB - During the last decade, several medications have been registered and marketed in osteoporosis. They have demonstrated their anti-fracture efficacy. Subsequently, the clinical management of osteoporosis becomes more sophisticated and complex. Bisphosphonates (alendronate, risedronate, ibandronate) have demonstrated their efficacy on the axial and appendicular skeleton. On scientific grounds, it seems difficult to distinguish between them, in terms of efficacy and/or safety. A special interest should be focused on the optimisation of patients' adherence, which remains poor with the daily and weekly formulations. Raloxifene, a selective estrogen receptor modulator, has shown anti-fracture efficacy at the level of the lumbar spine and, also, exerts collateral benefits on the breast. The peptides from the parathyroid hormone family are stimulators of bone formation. They showed anti-fracture efficacy at the axial and appendicular skeleton. Due to their prohibitive cost, their use should be restricted to patients with severe osteoporosis. Strontium ranelate, with its unique mode of action combining inhibition of bone resorption and stimulation of bone formation, is characterized by a wide scatter of activity, both in terms of skeletal sites positively affected and of patients experiencing benefits of its administration. Currently, it is the only drug which has shown an extensive anti-fracture efficacy in elderly subjects over 80 years old. PMID- 17725207 TI - [New management of phosphocalcic abnormalities in dialysis patient]. AB - Disorders of the phosphocalcic metabolism are frequent in dialysis patients. Such disorders are difficult to treat and have negative impact on bone health, but also on cardiovascular mortality. Hyperphosphoremia is a strong predictor of cardiovascular mortality. New phosphate binders are now available in Belgium. A new molecule acting on the calcium receptor of the parathyroid glands is able to control secondary and tertiary hyperparathyroidism in dialysis patients. These new therapies, specific for dialysis patients, will be reviewed in this article. PMID- 17725208 TI - [Anemia and cardiovascular risk in the chronic kidney disease population--which hemoglobin target should be reached?]. AB - Anemia is frequent when chronic kidney disease develops. Its correction by the use of erythropoietin improves the quality of life, and exercise tolerance, and decreases the cardiovascular risk. However, this later risk is not further decreased or even is increased when the hemoglobin target is set above 13 g/dl as compared to the recommended hemoglobin level between 11 and 12 g/dl. This last target therefor gives the best cost-beneficial effect ratio in the chronic kidney disease population. This target must be the new one. PMID- 17725209 TI - [What's new in immunosuppression for renal transplantation?]. AB - The goal of immunosuppression in transplantation is to prevent acute rejection and, more recently, chronic renal graft rejection related in part to side-effects of immunosuppressive therapy (hypertension, diabetes, dyslipidaemia,..). The development of new drugs in renal transplantation has improved graft survival, but also the patient's quality of life. A better understanding of the side effects of immunosuppressive therapy and the observation of optimal drug associations to reduce these side-effects have often led to propose modifications of the immunosuppressive regimen, mainly at the end of the first trimester after renal transplantation. The aim of this overview is to describe the available oral immunosuppressive agents, especially the new ones, their advantages, but also the danger when different drugs are added in acute illness. PMID- 17725210 TI - [New treatments of infectious diseases over the last ten years]. AB - This review focuses on new antibiotics, particularly for gram-positive infections, new antiretroviral drugs, new treatment of fungal infections and indications of miltefosine in the treatment of leishmaniasis. PMID- 17725211 TI - [Current therapies in hematology]. AB - This article focuses on recent advances in four important areas of hematology: aggressive lymphomas, allogeneic hematopoietic stem cell transplantation, multiple myeloma, and molecular therapy of cancer. PMID- 17725212 TI - [Current therapeutic progress in oncology: the development of targeted therapies]. AB - Over the last decades, significant advances were make in basic research as concerns the malignant transformation of normal cells. As a result, new targets for treatment were identified. "Targeted therapies" indicates that treatments are directed against specific molecular targets that play a major role in the activation of cell division and in the growth and dissemination of tumors. In particular, targeted therapies were developed against epithelial growth factor receptors and angiogenesis. We can expect specifise therapies against many other targets in the near future. Several drugs have obtained a marketing license. Predictive factors for tumor response and long term outcome should be developed for a better selection of the patient population who will benefit from these treatments. New imaging techniques are under development in order to assess the molecular response to these new approaches. PMID- 17725213 TI - [Innovative technologies in radiation oncology]. AB - At present, radiation oncology is again flourishing thanks to the development of highly accurate techniques as intensity modulated radiation therapy, stereotactic radiation therapy and hadrontherapy. These therapeutic modalities are made possible by the advent of image guided radiation therapy and respiratory gating that allows a better patient repositioning during the irradiation and between fractions. Nowadays, thanks to these recent technological advances, one can more easily conceive dose escalation, hypofractionation and combined treatment of radiation with sensitizing drugs and this together with a better protection of normal tissue aiming at, simultaneously, improved tumour control and better quality of life. This article describes these innovative technologies that, when integrated to other anti-tumoral therapeutic modalities, seem to be very promising. PMID- 17725215 TI - [Recent advances in breast cancer surgery: the sentinel-node biopsy technique]. AB - Sentinel lymph node biopsy is progressively replaces axillary conventional dissection for the treatment of breast cancer. In patients with small breast tumours avoiding axillary clearance and its potential morbidity is an important advance in the quality of care. The technique, detailed in this paper, is robust, safe and widely used today. Nevertheless it is not always well understood, and is in constant evolution regarding both the technique and the interpretation of its results. PMID- 17725214 TI - [Recent advances in the treatment of brain tumours]. AB - Neuronavigation is a tool for image guidance surgery. Based on the principle of the GPS, it is notably used for the ablation of brain tumors. Because of their millimetre precision, neuronavigation devices bring more safety and effectiveness due to the ever increasing performances of medical imaging. However, neuronavigation presents a major pitfall as it uses a static support (the images acquired preoperatively) to perform a dynamic process (the surgical ablation). To preserve the performance of neuronavigation, it is mandatory to update the images during surgery. This is now achievable by interventional MRI, intra-operative ultrasound and the incorporation of fluorescent tracers by the tumor cells. These major tools, now available at Sart Tilman University Hospital of combined with state-of-the-art chemotherapy, radiotherapy and experimental protocols (including gene therapy) will undoubtedly improve the prognosis of brain tumors. PMID- 17725216 TI - [Therapeutic progress in gynecology: organic diseases]. AB - Over the last ten years, progress in evidence-based medicine coupled with technological and surgical breakthroughs have deeply changed the management of our patients. Uterine bleeding is the first cause of gynaecological consultation and the intrauterine progestin delivery system as well as new hysteroscopic procedures have optimized the therapeutic approach to this problem. Introduction of magnetic resonance imaging and interventional procedures have improved breast disease diagnosis and management; likewise sentinel node localization, introduction of aromatase and growth factors inhibitors, new radiotherapy procedures and pharmacogenomics, have helped to ameliorate breast cancer treatment. Pelvic surgery has been switching more and more towards laparoscopic procedures not only in the field of benign lesions (eg endometriosis), of surgery of prolapse and incontinence with new prosthetic materials, but also for an improved management of gynaecological cancers. PMID- 17725217 TI - [Therapeutic progress in gynecology: functional approaches]. AB - Over the last ten years, progress in evidence-based medicine coupled with technological breakthroughs and introduction of new drugs have deeply changed the management of our patients. In the field of hormone therapy, lower dosages of estrogens and new progestins have increased tolerance and non-contraceptive benefits of oral contraceptives, while lower-doses, new progestins, new routes of administration have optimized the benefit/risk balance for the treatment of menopause. About 500,000 cycles of IVF are performed worldwide each year, optimizing male and female fertility, with less multiple pregnancies, and use of new recombinant gonadotropin, LHRH agonists/antagonists, new ovarian tissue cryopreservation techniques, etc... PMID- 17725218 TI - [Update in tocolysis]. AB - Preterm birth is the most common underlying cause of perinatal morbidity and mortality in nonanomalous infants. Treatment of preterm labor with tocolytic medication is an important part of improving perinatal outcome. Choosing a tocolytic agent requires consideration of efficacy and safety. It is the aims of the present research. PMID- 17725219 TI - [Therapeutic armamentarium in neurology: the birth of a new era]. AB - The field of neurology was long infamous for a lack of therapeutic options. How many of you have once thought: "Neurologists don't cure the disease, they admire it". But those days have passed into history, and the field is now vibrant with new treatments and hope even for patients with the worst neurodegenerative diseases. We summarized in the present review the latest major advances in therapeutic principles and practice for some of the most frequent chronic neurological disorders such as headaches, epilepsy, multiple sclerosis, dementias, Parkinson's disease, sleep/wake disturbances and peripheral neuropathies. We cannot cure or prevent, but we can now halt or control symptoms and disease progression to provide physical and psychological relief, and a better quality of life for patients who suffer from these otherwise devastating neurological conditions. PMID- 17725220 TI - [Update in drug therapy in neuropediatry]. AB - The most recent antiepileptic drugs used in children are lamotrigine, topiramate, oxcarbamaz6pine and levetiracetam. Their efficacy is proven, depending on the type of crisis, but in Belgium they are reimbursed only in certain conditions. The treatment of children with attention deficit hyperactivity disorder (ADHD), which was only constituted of methylphenidate, can now benefit from atomoxetine whose mechanism of action is different. PMID- 17725221 TI - [New prospects in the treatment of affective disorders]. AB - Remission and prevention of recurences are the main objectives in the management of affective disorders. If it is assumed that remission is the ultimate objective of treatment in affective disorders, it is important to be aware of the most effective therapeutic strategies available for achieving this state. However, with conventional agents, several patients are nonresponders or exhibit only a partial response to initial treatment. Thanks to a better understanding of pathophysiological mechanisms of affective disorders, new therapeutical strategies have been developed. The future will include the developement of new original pharmacological agents outside the field of the classical monoaminergic hypothesis of depression. PMID- 17725222 TI - [Cutaneous adverse reactions to chemotherapy and their management]. AB - Chemotherapy is an essential component in the multidisciplinary management of many cancers. Skin reactions to chemotherapeutics are rather frequent, and their morbidity may be significant. It is wise to identify them with precision in order to chose the most adequate preventive and therapeutic measures. The dermatopathology assessment is helpful for the diagnostic. PMID- 17725223 TI - [Can we sort out from the jumble about oral contraceptives and skin cancers?]. AB - Skin contains various hormonal receptors, particularly those for estrogens, progesterone and androgens. Steroid hormones of oral contraceptives affect the skin, in particular the control of the cell cycle, DNA replication, apoptosis and other cellular functions. Some estrogen-responsive pathways have the potential to promote tumor development. The question of whether oral contraceptives increase the risk for the development of skin cancer, particularly melanoma, remains an area of concern. There is some evidence that steroid hormones present in oral contraceptives do not significantly increase the risk of developing skin cancer when estrogen exposure is not excessive. PMID- 17725224 TI - [Overview of a decade of advances in ophtalmology]. AB - This review summarizes the most important advances that occurred in ophthalmology during the last decade, with a focus on corneal pathology, cataract surgery, glaucoma and retinal diseases. PMID- 17725225 TI - [Epilogue of the "therapeutic memory"...]. PMID- 17725226 TI - Major microbiology research areas and techniques: cell division, cytoskeleton, stationary-phase and bioluminescence. PMID- 17725227 TI - Of the morphogenes that make a ring, a rod and a sphere in Escherichia coli. AB - In 1993, William Donachie wrote "The success of molecular genetics in the study of bacterial cell division has been so great that we find ourselves, armed with much greater knowledge of detail, confronted once again with the same naive questions that we set to answer in the first place". Indeed, attempts to answer the apparently simple question of how a bacterial cell divides have led to a wealth of new knowledge, in particular over the past decade and a half. And while some questions have been answered to a great extent since the early reports of isolation of division mutants of Escherichia coli, some key pieces of the puzzle remain elusive. In addition to it being a fundamental process in bacteria that merits investigation in its own right, studying the process of cell division offers an abundance of new targets for the development of new antibacterial compounds that act directly against key division proteins and other components of the cytoskeleton, which are encoded by the morphogenes of E. coli. This review aims to present the reader with a snapshot summary of the key players in E. coli morphogenesis with emphasis on cell division and the rod to sphere transition. PMID- 17725228 TI - Intracellular cytoskeletal elements and cytoskeletons in bacteria. AB - Within a short period of time after the discovery of bacterial cytoskletons, major progress had been made in areas such as general spatial layout of cytoskeletons, their involvement in a variety of cellfunctions (shape control, cell division, chromosome segregation, cell motility). This progress was achieved by application of advanced investigation techniques. Homologs of eukaryotic actin, tubulin, and intermediate filaments were found in bacteria; cytoskeletal proteins not closely or not at all related to any of these major cytoskeletal proteins were discovered in a number of bacteria such as Mycoplasmas, Spiroplasmas, Spirochetes, Treponema, Caulobacter. A structural role for bacterial elongation factor Tu was indicated. On the basis of this new thinking, new approaches in biotechnology and new drugs are on the way. PMID- 17725229 TI - The sigmaS subunit of RNA polymerase as a signal integrator and network master regulator in the general stress response in Escherichia coli. AB - The sigmaS (RpoS) subunit of RNA polymerase in Escherichia coli is a key master regulator which allows this bacterial model organism and important pathogen to adapt to and survive environmentally rough times. While hardly present in rapidly growing cells, sigmaS strongly accumulates in response to many different stress conditions, partly replaces the vegetative sigma subunit in RNA polymerase and thereby reprograms this enzyme to transcribe sigmaS-dependent genes (up to 10% of the E. coli genes). In this review, we summarize the extremely complex regulation of sigmaS itself and multiple signal input at the level of this master regulator, we describe the way in which sigmaS specifically recognizes "stress" promoters despite their similarity to vegetative promoters, and, while being far from comprehensive, we give a short overview of the far-reaching physiological impact of sigmaS. With sigmaS being a central and multiple signal integrator and master regulator of hundreds of genes organized in regulatory cascades and sub-networks or regulatory modules, this system also represents a key model system for analyzing complex cellular information processing and a starting point for understanding the complete regulatory network of an entire cell. PMID- 17725230 TI - Illuminating cellular physiology: recent developments. AB - Bioluminescent methods are gaining more and more attention among scientists due to their sensitivity, selectivity and simplicity; coupled with the fact that the bioluminescence can be monitored both in vitro and in vivo. Since the discovery of bioluminescence in the 19th century, enzymes involved in the bioluminescent process have been isolated and cloned. The bioluminescent reactions in several different organisms have also been fully characterized and used as reporters in a wide variety of biochemical assays. From the 1990s it became clear that bioluminescence can be detected and quantified directly from inside a living cell. This gave rise to numerous possibilities for the in vivo monitoring of intracellular processes non-invasively using bioluminescent molecules as reporters. This review describes recent developments in the area of bioluminescent imaging for cell biology. Newly developed imaging methods allow transcriptional/translational regulation, signal transduction, protein-protein interaction, oncogenic transformation, cell and protein trafficking, and target drug action to be monitored in vivo in real-time with high temporal and spatial resolution; thus providing researchers with priceless information on cellular functions. Advantages and limitations of these novel bioluminescent methods are discussed and possible future developments identified. PMID- 17725231 TI - Recognition by French courts of compensation for post-vaccination multiple sclerosis: the consequences with regard to expert practice. AB - Over the past few years, despite scientific uncertainties, French courts have awarded compensation to sufferers of multiple sclerosis (MS) which occurred following vaccination against hepatitis B. These legal decisions have aroused fierce criticism in the medical world. Both a judgment given on 25 May 2004 by the Court of Cassation and a new publication in the journal Neurology have encouraged us to look once more at this controversial issue. French judges began compensating patients with MS at the end of the 1990s. One of the first judgments was given in 2001 by the Court of Appeal of Versailles when a pharmaceutical laboratory was held liable for the onset of MS following vaccination against hepatitis B. On appeal, the Court of Cassation overturned the judgment in September 2003, finding that the Court of Appeal judges had based their decision on a hypothetical causal link. However, the only reason why the Court of Appeal judgment was quashed was the contradictory evidence on which the judges had based their presumptions. Several of the judgments given since that date seem to confirm this hypothesis. On 25 May 2004, the 2nd civil law chamber recognized that MS which occurs following a vaccination against hepatitis B (a vaccination carried out for work-related purposes) could be considered as an accident at work, without questioning the possible causal link between the illness and the vaccine. This jurisprudence in the matter of hepatitis B vaccination shows the need for great care in expert practice. Effectively, when confronted with drug related imputability, the expert usually bases his reasoning on three points: the causal role of the generating factor, the chronology and other causes of damage. In terms of MS, all these factors are modified. More than ever, an expert must, in terms of imputability, be objective, prudent and clear in his conclusions. PMID- 17725232 TI - Insomnia in places of detention: a review of the most recent research findings. AB - Up to 40% of prisoner patients in a general medicine outpatient service seek medical consultation for sleep problems. This paper provides a brief overview of what is known about insomnia and its treatment from studies on non-detained patients and discusses the relevance of the findings from studies in liberty for prison health care. The clinical and ethical issues of insomnia in prison are described, followed by a summary of the existing studies on insomnia in prison. The results of the reported studies show that insomnia in places of detention should not be reduced to a secondary problem related to substance abuse and mental illness, as it appears to be an independent situational problem. Correctional health care physicians' evaluation of insomnia is insufficient. Drug prescription works well in some patients, but has a limited effect on insomnia relief in others. A clear need exists for the education of prison health care professionals on insomnia evaluation and management. Additional non pharmacological treatment in the prison health care setting should be used more frequently. Prison health care services should develop clear guidelines based on research evidence about insomnia and which contain treatment recommendations based on the principle of equivalence of health care outside and inside places of detention. PMID- 17725233 TI - Rib fractures in infancy: establishing the mechanisms of cause from the injuries- a literature review. AB - In the absence of a history of a significant accidental event, the most likely diagnosis in an infant with rib fractures is non-accidental injury. Medical opinion is essential when deciding if child abuse has taken place or not and this requires a consideration of whether a proposed causal explanation fits with the observed injuries. To assist in the interpretation of injuries and inform medical practitioners, it is essential to develop a clear understanding of their biomechanical mechanism of causation. The types and 'likely' mechanisms of rib fracture are well-documented, however, what forces, deflections and loading rates are required to produce particular fractures are relatively unknown. This paper presents a review of the literature, from a biomechanical engineering perspective, to assess information regarding the various types of rib fracture and their likely mechanisms, paying particular attention to the likely forces, deflections and loading rates involved. The biomechanical parameters, applied during 'two finger' infant cardiopulmonary resuscitation (CPR), are identified and discussed, and are currently believed to be below the limit at which rib fracture may occur. However, a new 'two thumb' CPR technique is identified which involves a holding/gripping mechanism of the infant thorax, similar to that which is believed to occur in inflicted injury scenarios, such as shaking. The two thumb method may provide a greater magnitude of force and deflection, a greater rate of loading and may perhaps pose a greater risk of fracture, compared with the 'two finger' supine, anterior-posterior chest compression approach. It is proposed to introduce a force/deflection boundary condition into mechanical and computer/numeric infant models. Subject to the future inclusion of loading rate/response data, a three-dimensional (force/deflection/loading rate) boundary condition will be used to provide a minimum injury threshold for potentially injurious scenarios. A number of further studies are suggested, since this paper is intended to provide a first step to developing a more sophisticated understanding of the causes of infant rib fracture. Areas of further study include specific rib fracture mechanisms, as well as the effects of age dependent characteristics, positioning and area of force application. Such additional information would allow the proposed initial boundary condition to be further refined to provide an indication of the likelihood, type and number of fractures that might be expected. PMID- 17725234 TI - Characteristics of mentally disordered offenders referred for low secure forensic rehabilitation. AB - In the light of recognition of an increased need for secure mental health provision both at a local and national level, a 12-bed low secure forensic rehabilitation unit, Hillis Lodge, was opened in Birmingham in 2001. The aim of this study was to investigate characteristics of patients referred to this service. A retrospective case note survey was undertaken of all referrals to Hillis Lodge between August 2000 and April 2004. A comparison was then made between the accepted group and those not accepted for admission to identify characteristics that may be associated with admission to a low secure forensic unit. For the referred sample, mean age was 38 years (range 23-65 years, SD = 9.17) and in 86.4% of cases the primary diagnosis was schizophrenia. Those accepted were more likely to be detained under Part III sections of the Mental Health Act 1983 and have a greater number of previous convictions. By identifying need in this particular patient sample, this study has helped to inform the assessment process and treatment programmes in a low secure forensic rehabilitation service. PMID- 17725235 TI - Attitudes of psychiatrists towards forensic psychiatry: a survey. AB - Forensic psychiatry has been rapidly expanding in recent years and more NHS forensic beds are planned. This study aimed to examine the attitudes of psychiatrists towards forensic psychiatry. A questionnaire was given to psychiatrists attending a regional Royal College of Psychiatrists conference. In addition forensic psychiatrists were surveyed in the two local regional secure units. Ninety-eight psychiatrists, including twenty-four forensic psychiatrists, completed the questionnaire. Forensic and non-forensic psychiatrists tended to agree with the expansion in forensic beds. Non-forensic psychiatrists wanted a lower threshold for admission to secure units. Forensic psychiatrists disagreed. Non-forensic psychiatrists tended to feel that forensic psychiatry has been over funded compared with other psychiatric services. They also commented that forensic services should integrate more closely with other non-secure psychiatric services and should offer more community forensic services rather than concentrating care on in-patients. Forensic services should consider what services they provide and try to meet the desires of secondary services, such as more community forensic services and greater integration with other psychiatric services. PMID- 17725236 TI - Applying visible hyperspectral (chemical) imaging to estimate the age of bruises. AB - Hyperspectral (chemical) imaging collects spectroscopic data in a two-dimensional spatial format. The potential application for the determination of the age of bruises is demonstrated and compared to reflectance probe spectrophotometry as well as photography. Blood was deposited on white cotton cloth or injected subcutaneously into pig skin to simulate a 'fresh bruise'. A mixture of blood and bile was used to simulate 'old' bruises. On the cloth background all the photographic methods clearly separated the two groups of samples (i.e. 'blood only' from 'blood plus bile'). However, on the pig skin the two groups could be separated by one of the photographic methods only. Separation of blood from blood and bile mixtures was obtained on the cloth and skin backgrounds using spectrophotometry and hyperspectral imaging. In a test using serial dilutions of blood and bile mixtures, the hyperspectral system performed slightly better than the spectrophotometer. The former also had the advantage of imaging a wider area and providing spatial data. Hyperspectral (chemical) imaging and spectrophotometry are superior to photography for the detection of bilirubin on a background of skin (due to the presence of yellow chromophores); this technology combined with mathematical analysis of the spectral data warrants further investigation. PMID- 17725237 TI - Gender differences amongst adult arsonists at psychiatric assessment. AB - Reports of gender differences amongst arsonists at psychiatric assessment are not uncommon, however some are based on relatively small samples. A new retrospective study highlighting gender differences could help to confirm or refute the current state of knowledge. The aim of the current study was to examine gender differences amongst a sample of 167 adult arsonists (129 males and 38 females). Information was collected from clinical records on sociodemographic, family background and childhood factors; adult adjustment; fire setting history; motives; features of pyromania and other offending, from the case notes of a group of arsonists referred to the West Midlands Psychiatry Service over a 24 year period. Female arsonists were older than males and more likely to have a psychiatric diagnosis. Women more frequently had a history of sexual abuse, while men had a more varied criminal background and more substance abuse problems. Our findings largely support previous research, and are discussed in this context, whilst also bringing attention to a more recently developed theory (Action System Model). Significant gender differences amongst arsonists indicates that different emphases in the treatment of male and female arsonists may be advisable, though a reliable evidence base for treatment has yet to be established. PMID- 17725238 TI - A study of wound fatalities in the north of Jordan. AB - The aim of the present study is to analyze the epidemiological and demographic features of sharp wound fatalities. A retrospective study was carried out of 58 fatalities from injuries induced by the use of sharp objects which were sent to the Forensic Medicine Teaching Centre of North Jordan--affiliated to Jordan University of Science and Technology--for the period January 1989 to December 2000. Results showed that the majority of cases (46-79.31%) were young people, below 30 years of age. Forty-six cases were male (79.31%) and 12 (20.69%) were female. The 58 cases sustained 182 injuries. The trunk sustained the maximum number of injuries 145 (79.63%). Sharp wound fatalities showed a slight variation over the 12-year study period and rose twice, in 1991 and 2000. Forty four cases (75.86%) were urban residents. Thirty-seven (63.79%) cases occurred during the warmer months of the year. Most cases were murder 47 (81.03%) and 51 (88%) victims died from acute haemorrhagic shock. Forty-three (74.14%) cases died before receiving any treatment. None of the 58 victims had used alcohol or drugs. One victim was a Syrian labourer. Cases of sharp wound fatality were more or less stable with two peaks in 1991 and 2000. As in other parts of the world, most victims were young males living in urban areas under stressful conditions. Socio cultural factors have reduced the frequency of fatalities. PMID- 17725239 TI - Elderly suicide rates: cross-national comparisons and association with sex and elderly age-bands. AB - Suicide rates generally increase with age. Examination of cross-national variations in elderly suicide rates may allow the generation of aetiological hypotheses. Suicide rates for males and females in the age-bands 65-74 years and 75+ years were ascertained from the World Health Organisation website for all the listed countries. Cross-national variations were examined by segregating different countries into four quartiles of elderly suicide rates. Suicide rates between males and females and between the two age-bands were compared across different countries. The main findings were: (i) there is wide cross-national variation in elderly suicide rates; (ii) elderly suicide rates were the lowest in Caribbean, central American and Arabic countries, and the highest in central and eastern European, some oriental and some west European countries; (iii) suicide rates were higher in men compared to women for both the age-bands; and, (iv) suicide rates were higher in the age-band 75+ years compared to the age-band 65 74 years for males and females. Potential explanations for regional and cross national variations in elderly suicide rates include cross-national differences in genetic and environmental factors, prevalence of mental illness in the elderly, life expectancy, socio-economic deprivation, social fragmentation, cultural factors, the availability of appropriate healthcare services, and public health initiatives to improve the detection and treatment of mental illness, mental health and suicide prevention. PMID- 17725240 TI - Mentally disordered offenders in Zimbabwe and in England and Wales: a socio demographic study. AB - Our aim was to compare socio-demographic, clinical and criminal characteristics of mentally disordered offender patients in a special institution in a developing and a developed country. Zimbabwe data from 1980-1990 was obtained from a hospital patient survey, in a written semistructured format. The English special (high security) hospital patients' data for the same period was obtained from the case register. The sample size for Zimbabwe was 367 patients (337 males, 30 females) and for England and Wales it was 1,966 patients (1,643 males, 323 females). The average age for Zimbabwean patients was 36 years, with standard deviation of 9.7; for England and Wales the average age was 29.7 with standard deviation of 9.6. There was significant difference in marital status in the two countries. Seventy-eight per cent of patients were single in England and Wales, compared with 49% in Zimbabwe. There were 20% illiterate patients in Zimbabwe, compared with 4% in England and Wales. Thirty-seven per cent of the patients in England and Wales had a diagnosis of personality disorder, compared with 6% in Zimbabwe. There were 53% of homicides in Zimbabwe, compared with 20% in England and Wales. Employment in the two countries was similar: 34% in Zimbabwe and 33% in England and Wales. There were differences in the socio-demographic characteristics in the two countries, except for employment status. Differences were also noticed in the diagnoses of the patients, types of crime and the methods of assault. PMID- 17725241 TI - Utility of the caput succedaneum in the forensic investigation of neonaticide: a case report. AB - Suspicion of neonaticide often leads to a request for a forensic autopsy. In that setting, it is important to correlate autopsy findings with the history given by the mother. So far, caput succedaneum has not raised interest in forensic pathology. A caput succedaneum is a haemorrhagic oedema involving the skin and superficial fascia of the head that results from circulatory stasis caused by compression exerted by the uterus or cervix on the presenting part. It is usually seen with prolonged labour. We report a case of caput succedaneum in a forensic autopsy that overturned the mother's history of giving birth suddenly, consequently increasing the evidence of neonaticide. PMID- 17725242 TI - Medical litigation as a result of awareness during general anaesthesia: a case report. AB - In the literature, little attention has been paid to the medico-legal implications of awareness during general anaesthesia, a complication which has been reported with an incidence of 0.5-2%. We present the case of a 39-year-old nurse who experienced awareness during salpingo-adnexectomy for tubo-ovarian pregnancy. The operation was performed as an emergency, due to severe haemorrhage. Anaesthesia was induced with 125 mg of thiopental sodium and 60 mg of succinylcholine, and then maintained with repeated doses of fentanyl and 7 mg of vecuronium. In the court settlement, medical liability was rejected, because her awareness during anaesthesia was ascribed to the need to use small quantities of anaesthetics, due to severe hypotension, and not to medical error. The case presented here and a brief review of the literature indicate that awareness during anaesthesia is not always a consequence of medical negligence. PMID- 17725243 TI - Unplanned complex suicide by self-strangulation associated with multiple sharp force injuries: a case report. AB - In cases of ligature strangulation, the importance of distinguishing self inflicted death from homicide is crucial. This entails objective scene investigation, autopsy and anamnesis in order to elucidate the manner of death correctly. The authors report a case of unplanned complex suicide by means of self-strangulation and multiple sharp force injury. The use of more than one suicide method, consecutively--termed unplanned complex suicide--gives this case particular significance. A brief discussion on this uncommon method of suicide is presented, particularly relevant to the attending forensic physician. In addition, a short overview of the entity of complex suicide is given. PMID- 17725244 TI - Effects of high-dose itraconazole treatment on lipoproteins in men. AB - OBJECTIVE: Epidemiological studies have convincingly demonstrated a positive association between LDL-cholesterol (LDL-C) and coronary artery disease but, in the case of HDL-C, there is an inverse association. Administration of high doses of the antifungal agent ketoconazole (800 mg/d) reduces serum concentrations of total cholesterol and LDL-C and there is a tendency for an increase in HDL-C. Our goal was to examine whether high-dose itraconazole raises HDL-C in subjects with normal levels of cholesterol. PATIENTS AND METHODS: 8 male patients with onychomycosis received 2 one-week cycles of treatment with itraconazole at a dose of 400 mg once daily in an open, prospective exploratory trial. Serum levels of itraconazole and its active metabolite hydroxyitraconazole were determined using high-performance liquid chromatography at the end of each treatment cycle. Fasting levels of serum lipoproteins and triglycerides were measured twice using routine enzymatic assays at the beginning and end of each cycle. The effects of itraconazole and hydroxyitraconazole on HDL-C metabolism were assessed in vitro using a human Caco-2 cell line and analyzing apoA-I levels with an enzyme-linked immunosorbent assay. RESULTS: During itraconazole treatment total cholesterol and LDL-C decreased on average by 12% (p < 0.001) and 17% (p < 0.001), respectively, whereas HDL-C increased by 21% (p < 0.001). The ratio LDL: HDL-C, an index of atherogenic risk, decreased by 30% (p < 0.001). Incubation of Caco-2 cells in the presence of itraconazole and hydroxyitraconazole for 3 hours resulted in a significant increase in apoA-I concentration in the medium (913 and 412%, respectively) compared with control. CONCLUSION: In addition to its inhibitory effect on cholesterol synthesis, high-dose itraconazole (400 mg/d) causes a significant decrease in serum LDL-C and, in contrast to ketoconazole, a significant increase in HDL-C. In vitro studies with Caco-2 cells indicate that the latter observation might be caused by an increase in apoA-I levels. PMID- 17725245 TI - Pharmacodynamic effects of orally administered dexlipotam on endothelial function in type 2-diabetic patients. AB - OBJECTIVE: Diabetic endotheliopathy is the result of hyperglycemia and the production of oxygen-free radicals. In vitro and in vivo data have shown beneficial effects of dexlipotam (DEX), a tromethamine salt of R(+)-alpha-lipoic acid, on oxidative stress in hyperglycemic states, but no data are available on the effects of this agent on endothelial function. The purpose of this pilot study was to evaluate the impact of DEX on endothelial function in patients with type 2 diabetes (DM2) and to estimate the safety and tolerability of DEX. MATERIAL AND METHODS: DEX 960 mg and DEX 1,920 mg were investigated in DM2 patients over a period of 4 weeks using a randomized, placebo- (PLA) controlled, double-blinded study with 3 parallel groups. The marker of arterial function after 4-week therapy with DEX was the maximum percentage change versus baseline in the flow-mediated dilation of the brachial artery (FMD) after reperfusion. RESULTS: A total of 114 diabetic patients were randomized to the three study groups. DEX was safe and well tolerated. Dyspepsia appeared to be the most relevant side effect of DEX treatment. Systolic (p = 0.078) and diastolic blood pressure (p = 0.059) tended to be lower in patients treated with DEX at a dose of 1,920 mg. There were no significant differences in FMD between the placebo- and the DEX-treated groups. In patients with poorer glucose control (HbA1c > 6.5% Hb), FMD increased significantly after 4-week treatment with DEX: PLA -1.51 +/- 2.98%, DEX 960 mg +1.22 +/- 3.22, p = 0.027, DEX 1,920 mg +1.47 +/- 3.78, p= 0.012. The magnitude of the mean change compared to placebo was 2.73% (DEX 920) and 2.98% (DEX 1,920) in patients with HbAlc > 7.5% Hb (DEX 960, p = 0.007, DEX 1,920, p = 0.032). The effects of treatment were usually statistically significant in subgroups with more severe vascular stress (longer duration of disease, pretreatment history, higher LDL-C, higher blood pressure). CONCLUSION: DEX therapy appears to reduce endothelial dysfunction in DM2, especially in men with long history of DM2 and having poor glucose control. These findings will be useful in patient selection in future prospective clinical trials with drugs to treat vascular stress. PMID- 17725246 TI - Effects of sympatholytic therapy on insulin sensitivity indices in hypertensive postmenopausal women. AB - Cardiovascular risk factors are often ineffectively controlled in hypertensive postmenopausal women, and moreover, some antihypertensive drugs may increase particular risk factors such as insulin resistance. In a multicenter, multinational (Finland, Sweden, Lithuania), double-blind, prospectively randomized study hypertensive obese postmenopausal women without hormone therapy (n = 98) were randomly assigned to receive treatment with either the centrally acting agent moxonidine, 0.6 mg/day, or with the peripherally acting atenolol, 50 mg/day, for 8 weeks. In addition to blood pressure measurements, insulin sensitivity was estimated by the quantitative insulin sensitivity check index (QUICKI) and by the insulin sensitivity index (ISI-Matsuda). Subgroup analysis in insulin-resistant women (fasting P-insulin > or = 10 mU/l) and blood pressure responders (diastolic blood pressure < or = 90 mmHg and/or reduction of blood pressure > or = 10 mmHg) were also carried out. Both atenolol and moxonidine led to a significant reduction in diastolic blood pressure of 9.5 mmHg and 6.2 mmHg, respectively. Among insulin-resistant women, an increase in the insulin sensitivity assessed by ISI was improved with moxonidine treatment (p = 0.025). A decrease in insulin sensitivity assessed by QUICKI was observed with atenolol treatment in women with fasting insulin level < 10 mU/l. In patients, in whom blood pressure was reduced, an improvement in insulin sensitivity (ISI) was associated with moxonidine treatment (p = 0.019), but not with atenolol treatment. The centrally acting sympatholytic agent moxonidine did reduce blood pressure somewhat less than atenolol, but it was associated with an improved metabolic profile in terms of decreased insulin resistance both in insulin resistant postmenopausal women and in women with a significant blood pressure response. PMID- 17725247 TI - Validation of limited sampling models (LSM) for estimating AUC in therapeutic drug monitoring--is a separate validation group required? AB - OBJECTIVE: Limited sampling models (LSM) for estimating AUC in therapeutic drug monitoring are usually validated in a separate group of patients, according to published guidelines. The aim of this study is to evaluate the validation of LSM by comparing independent validation with cross-validation using the patient data from the development group. METHODS: The design of the Monte Carlo simulation study was similar to a study described in the literature, i.e. a development group of 20 patients receiving cyclosporine orally every 12 h. Blood samples were taken at 10 fixed time points. In total 20,000 patient data sets were generated by Monte Carlo simulation, taking into account interindividual variability and measurement errors. Accuracy (mean error, ME) and precision (root mean squared error, RMSE) were calculated for evaluation of the validation procedures, varying the time points of the samples used for the estimation of AUC to identify the optimal sampling time points. In addition, the influence of the number of samples and the number of subjects was investigated. RESULTS: Cross-validation resulted in values for ME and RMSE almost identical to values using a separate validation group with the same number of subjects as the development group. CONCLUSION: A separate validation group is not needed. The most efficient method is to use all patient data for the development of the LSM, and to assess the accuracy and precision by cross-validation. PMID- 17725248 TI - Lack of influence of CYP2D6 genotype on the clearance of (R)-, (S)- and racemic methadone. AB - OBJECTIVE: To investigate the influence of CYP2D6 genotype on the oral clearance of (R)-, (S)- and rac-methadone. METHODS: In this retrospective study, CYP2D6 genotypes were identified in 56 methadone maintained subjects. Plasma concentrations of (R)-, (S)- and rac-methadone were determined by stereoselective HPLC and sufficient data were available to estimate the apparent oral clearances of (R)-, (S)- and rac-methadone using a population kinetic model in 37 of the genotyped subjects. RESULTS: The CYP2D6 allele frequencies were similar to those previously reported in Caucasians, the most common being: CYP2D6*1 (35.2%), CYP2D6*2 (12.0%) and CYP2D6*4 (22.2%). Three unknown SNPs were found in four subjects: 1811G > A (n = 1), 1834C > T (n = 1) and 2720G > C (n = 2). The oral clearances of (R)-, (S)- and rac-methadone varied 5.4-, 6.8- and 6.1-fold, respectively. No significant differences in methadone oral clearance were found between CYP2D6 genotypic PM, IM and EM (p = 0.57, 0.40 and 0.43 for (R)-, (S)- and rac-methadone, respectively). Only 1 subject had duplication of functional CYP2D6 alleles and the oral clearance of the three analytes was not markedly altered. CONCLUSIONS: CYP2D6 poor, intermediate and extensive metabolizer genotypes did not appear to impact on the oral clearance of (R)-, (S)- or rac methadone. In addition, methadone dosage requirements were not influenced by CYP2D6 genotypes in these subjects. However, the impact of duplication of functional CYP2D6 alleles on oral clearance and dosage requirements requires further investigation. PMID- 17725249 TI - Lack of effect of rifalazil on ethinyl estradiol pharmacokinetics in healthy postmenopausal women. AB - Rifalazil, a second-generation rifamycin, is being evaluated for the treatment of sexually transmitted disease and gastrointestinal infections. We determined whether rifalazil influences CYP3A4 metabolism by studying the effect of a single oral, 25 mg dose of rifalazil administered to healthy postmenopausal women, on the steady-state pharmacokinetics (PK) of ethinyl estradiol (EE) during administration of Ortho-Novum 1/35 (EE/NET). Noncompartmental PK and sequential statistical analyses were performed to establish if and when subjects achieved steady-state EE plasma concentrations and to determine whether this steady state was altered by rifalazil administration. The geometric mean ratios for the difference between EE alone and following rifalazil for EE Cmax, AUC(0-24) and Cmin were 105.9, 104.4 and 105.0, respectively. The 90% confidence intervals for each ratio fell within 80 - 125% of the reference treatment indicating no significant difference in the PK of EE before or after rifalazil administration. The posterior probabilities for the true treatment differences of Cmax or AUC(0 24) being less than 20% were > 99.99% in both cases. Based on the results of this study, there is no CYP3A4-metabolic interaction between a single oral, 25 mg dose of rifalazil and EE for either induction or inhibition. Consequently, there is minimal threat of contraceptive failure when single doses of rifalazil are administered with EE/NET. A single dose of rifalazil 25 mg was well tolerated when administered concomitantly with a combination oral contraceptive (EE/NET) by healthy postmenopausal females. PMID- 17725250 TI - Develop strong procurement card programs to save and make money. PMID- 17725251 TI - Creating a 'culture of discipline' for your teams. PMID- 17725252 TI - [Invagination in children: not always ileocaecal]. AB - Three patients, two girls aged 10 and a boy aged 11, suffered from secondary intussusception. Two of the cases were mistakenly managed as an idiopathic or classic intussusception. Hydrostatic reduction with a contrast enema was thought to be successful when retrograde influx in the ileum was seen. As the intussusception recurred, a diagnostic laparoscopy was performed followed by laparotomy and surgical treatment. In both cases an ileo-ileal intussusception was found. In one case the lead point was a malignant lymphoma, in the other case probably an area of vasculitis associated with Henoch Schonlein purpura. The enema had only repositioned the ileocolic part of the intussusception. In the third patient, the ileo-ileal intussusception resolved spontaneously. Due to the location of the intus-susception, a lead point was suspected and a laparoscopy was performed. A Meckel's diverticulum was found and resected. The importance of looking for a lead point is emphasized when dealing with an intussusception in children over the age of 3, or with evidence of underlying disease. In such cases, the relative value of a contrast enema for diagnosis and reposition is emphasised. There should be a low threshold for further investigation, including diagnostic laparoscopy. PMID- 17725253 TI - [Parkinson's disease(s): recent insight into genetic factors]. AB - In recent years, 5 genes have been identified that are unambiguously associated with genetic forms of Parkinson's disease. These genes probably explain less than 10% of all cases of Parkinson's disease. Clinically, these genetic forms can closely resemble idiopathic Parkinson's disease. Mutation analysis could be considered in cases involving an age at onset before 45 years, a positive family history or atypical presentations. However, the role of genetic testing in clinical practice remains to be established. Dysfunction of the ubiquitin proteasome complex, abnormalities of the oxidative stress response and mitochondrial defects represent the three main disease mechanisms implicated in Parkinson's disease caused by these gene mutations. Further research is likely to contribute to the understanding and future treatment of idiopathic Parkinson's disease. PMID- 17725254 TI - [Invasive Lancefield group A streptococcal infections in the Netherlands]. AB - After a steady decrease in morbidity and mortality resulting from severe group A streptococcal (GAS) infections, the 1980s witnessed a resurgence of invasive GAS disease. As a result a nationwide laboratory-based surveillance for invasive GAS infections was conducted at the National Institute of Public Health (RIVM) from 1994 to 2003. The estimated annual incidence ranged from 2.0 to 4.0 cases per 100,000 individuals per year. The case-fatality rate was 18% overall but varied substantially depending on the manifestation of the disease. GAS infections may be complicated by toxic shock-like syndrome (TSS) which is caused by bacterial exotoxins. Case fatality among TSS cases was 59%. The M-protein that extends from the cell membrane is used for sub-typing GAS in > 150 different M-types. Increased intrinsic virulence has been reported in Streptococcus pyogenes of certain M-types, notably M1 and M3. In the Netherlands these M-types have been independently associated with fatality. Over the last 50 years the genome of these M-types appears to have become enriched with phage-encoded virulence factors, possibly contributing to the altered epidemiology of invasive GAS disease. Despite this genetic plasticity, GAS have remained uniformly susceptible to penicillin. In-vitro studies have shown that the administration of immunoglobulin G can have a neutralising effect in cases ofTSS but clinical studies have failed to provide any statistical support for this. PMID- 17725255 TI - [Clinical practice guideline 'Complex regional pain syndrome type I']. AB - The development and treatment ofthe complex regional pain syndrome type I (CRPS I) are a subject of much discussion. Using the method for the development ofevidence-based guidelines, a multidisciplinary guideline for the diagnosis and treatment of this syndrome has been drawn up. The diagnosis of CRPS-I is based on the clinical observation of signs and symptoms. For pain treatment, the WHO analgesic ladder is advised up to step z. In case of pain ofa neuropathic nature, anticonvulsants and tricyclic antidepressants may be considered. For the treatment ofinflammatory symptoms, free-radical scavengers (dimethylsulphoxide or acetylcysteine) are advised. In order to enhance peripheral blood flow, vasodilatory medication may be considered. Percutaneous sympathetic blockades may be used for a cold extremity ifvasodilatory medication produces insufficient effect. To decrease functional limitations, standardised physiotherapy and occupational therapy are advised. To prevent the occurrence of CRPS-I after wrist fractures, the use of vitamin C is recommended. Adequate perioperative analgesia, limitation of operation time and limited use of bloodlessness are advised for the secondary prevention of CRPS-I. Use of regional anaesthetic techniques can also be considered in this connection. PMID- 17725256 TI - [Diagnostic image (334). A man with a skin wound under the eye]. AB - A 44-year-old man with a facial skin wound after working with a motor lawn mower had an orbital and ocular penetration by a 2.4 cm metal wire, with endophthalmitis caused by a Klebsiella ozaenae. PMID- 17725257 TI - [Delirium after a fractured hip in more than one-third of the patients]. AB - OBJECTIVE: Inventarisation and evaluation of the incidence, risk factors, and prognosis of postoperative delirium in patients with a fractured hip admitted to a surgical ward. DESIGN: Descriptive study of patient records. METHOD: All patients with a fractured hip admitted to the surgical ward of the Jeroen Bosch Hospital, Den Bosch, the Netherlands, in 2004 were included and evaluated. Active multidisciplinary interventions for the recognition and treatment of delirium by non-pharmacological and pharmacological means take place in this surgical ward. The records of all patients from the surgical and geriatric wards were evaluated and the data were analysed statistically by means of univariate and multivariate logistic 'step-forward' regression analysis. RESULTS: 114 patients were included. The incidence of postoperative delirium was 37%. Older age was a significant risk factor for the development of delirium in both the univariate and the multivariate analysis after correcting for overestimation (p < 0.01). Several other factors, including sex, type of surgery, and medical history, had no effect on the risk of delirium. CONCLUSION: Delirium after a hip fracture is not rare; the most important risk factor is older age. PMID- 17725258 TI - [Manifest carcinoma of the glandula vestibularis major (Bartholin's gland), detected one year after an inguinal lymph-node metastasis]. AB - A 68-year-old woman had had a TNM stage-III rectal carcinoma at the age of 54 for which she had undergone a low anterior resection followed by postoperative radiotherapy and adjuvant chemotherapy with fluorouracil and levamisol. More than 10 years later she presented with a swelling in the right groin, which turned out to be a metastasis; this was a poorly differentiated carcinoma with some of the characteristics of a transitional epithelial carcinoma, for which no primary tumour was found. The lymph node was excised. One year later, a swelling was detected on the labium majus, caused by a poorly differentiated transitional epithelial carcinoma of the glandula vestibularis major (Bartholin's gland). The patient was treated by means ofhemivulvectomy and postoperative radiotherapy. PMID- 17725259 TI - [Fatal ecstasy intoxication in a 22-year-old man]. AB - A 22-year-old man was admitted to the hospital with an ecstasy (MDMA) intoxication which was accompanied by hyperthermia. The patient developed rhabdomyolysis with hyperkalaemia, hypoglycaemia and acidosis, followed by multiple organ failure with disseminated intravascular coagulation and cerebral oedema. Despite maximal symptomatic treatment, the patient died after 4 days. MDMA is a serotonin agonist but also has noradrenergic and dopaminergic effects. It is a popular drug in the Netherlands among young people and is often wrongly considered to be safe. The occurrence of serious side effects is unpredictable and can have fatal consequences. Especially hyperthermia as a side effect of MDMA is a potentially life-threatening complication. The treatment is mainly symptomatic and consists of cooling, fluids, treatment of electrolyte disturbances, and support for respiration and circulation. The usefulness of dantrolene in the treatment of MDMA-induced hyperthermia is controversial, but for now it is still recommended. PMID- 17725260 TI - [Hendrik Burger, editor-in-chief of the Dutch Journal of Medicine 1904- 1913]. AB - Hendrik Burger (1864-1957) became the sixth editor-in-chief of the Journal before gaining international fame as a professor of otorhinolaryngology. He was more a teacher than researcher, and his clinic in Amsterdam became an internationally renowned training centre. He advocated better public healthcare for children who were deaf/mute or had impaired hearing and founded schools for these children. A prolific writer, Burger contributed more than 400 papers to the Journal. PMID- 17725261 TI - [Metformin-related lactic acidosis in an 85-year-old woman]. PMID- 17725262 TI - [Critical remarks regarding guidelines based on scientific research]. PMID- 17725263 TI - Dangerous abbreviations: "U" can make a difference! AB - Dangerous abbreviations are also known as "error-prone abbreviations". They are referred to as "dangerous" or "error-prone" because they can lead to misinterpretation of orders and other communications, resulting in patient harm or death. Selected medication errors arising from the use of dangerous abbreviations are highlighted in this article, along with examples of such abbreviations and strategies to eliminate their use. This column is intended to enhance the awareness of practitioners who treat and care for critical care patients of the problems associated with using ambiguous abbreviations and to provide suggestions for associated safe practices. PMID- 17725264 TI - Exemplary care of the palliative patient: the journey shared. AB - Critical care involves caring for complex and acute needs of patients with life threatening conditions. Despite skilful interventions, there are times when the care needed by patients and their families is primarily palliative. In this article, the author focuses on examples of ways nurses can make the palliative care they provide exemplary. Based on findings of a research study of outstanding palliative care nurses, the researcher describes the possible effect providing excellent palliative care may have on both the patient and the caregiver. Critical care nurses are often called to stand in the shadow of grief that accompanies death. Yet in doing so, these caregivers can be molded into more caring and compassionate people, and more exemplary nurses. Nurses in critical care are challenged daily to meet the multiple needs of patients and their families. Though state of the art technology, medications and advanced skills may save many lives, there are times when the care that is required is palliative. It is in these instances that a nurse 's strength and courage may be tested. By taking up this challenge, and sharing the final journey with patients, a nurse may learn many lessons. In part, caregivers may come to see that sometimes death is neither an enemy, nor a failure. Rather, sometimes death can lead to a more joyous embracing of life. Sometimes death is the only way that suffering can be erased. This article includes a description of key ways critical care nurses may address the needs of patients who are palliative. Specifically, the themes of helping people live on, individualizing care, defending human dignity, sensitive listening, sharing hope, and keeping the promise to never abandon are described. These themes all fall under the overarching theme of simple gestures, which is also described in this report. PMID- 17725265 TI - Family perceptions of end-of-life care in an urban ICU. AB - OBJECTIVES: As most Canadians die in hospital, the final contact of family members with their loved ones is frequently in an unknown and uncomfortable environment. Family members are integral to the end-of-life decision-making process and are vital contributors to the comfort of dying patients. A quantitative study was conducted in three critical care areas where the stated goals were to provide not only quality care to patients, but also support to families. The researchers sought to determine levels of satisfaction with care, visitation, support, comfort and pain measures. METHOD: Three hundred surveys were mailed to next of kin who had a loved one die in the critical care areas of an urban tertiary care centre within the prior three years. Survey questions covered such issues as perceptions regarding the decision to stop life supports, access to the patient, access to physicians and nurses and information regarding the patient's status, support provided by the hospital, and organ donation attitudes. FINDINGS: Multiple regression analysis revealed that three factors predicted perceptions of overall quality of care: 1) being informed by nurses and physicians of any changes, 2) having the same group of nurses provide care, and 3) having one individual act as the family contact. Together these factors accounted for 52% of the variance in perceptions of care. Two factors accounted for 59% of the variance in dissatisfaction with the information received: 1) the perception that physicians did not spend enough time answering family questions, and 2) that the family was not present when the patient died. IMPLICATIONS: Consistency in nursing care and provision of information to family members may be difficult in the fast pace of an ICU, but are reasonable program objectives considering the positive influence this has on perceptions of care. Further, flexible visitation policies which maximize access between family members and both their dying loved one and health care professionals appear to have a beneficial effect on satisfaction. PMID- 17725266 TI - Improving pain management for critically ill and injured patients. AB - The under-treatment of pain continues to be a problem in patient care. Evidence shows a significant percentage of patients suffering with acute and chronic pain, despite the treatment options available. This must be addressed, as undertreating pain has a long list of negative outcomes. In this article, the author reviews the consequences of unrelieved pain, barriers to pain management, and recommendations for improvements. As health care professionals, nurses have a responsibility to advocate for patients and provide the best pain management possible. Efforts to improve pain management will help avoid complications, such as chronic pain syndrome, while improving comfort, function, and quality of life. PMID- 17725267 TI - [Higher order aberrations in physiological optical system--own experience]. AB - PURPOSE: To assess higher order aberrations in the physiological optical system in relation to pupil diameter and age of people studied. MATERIAL AND METHODS: The study comprised 235 eyes of 122 subjects (67 women and 55 men) (mean age 43.8 +/- 15.5 years). Aberrations of the optical system were assessed using a LADARWave aberrometer (Alcon Laboratories). Aberration finding analysis included age, the pupil diameter, and their interrelations. ANOVA, Kruskal-Wallistest, multiple comparison and Ch2 tests were used to establish the statistical significance, and the correlation coefficient was calculated according to Spearman test. RESULTS: Basing on the studies performed, we found that the older subjects were the more statistically significant was the increase in the prevalence of higher order aberrations, including coma and spherical aberrations, at the same pupil diameter of 5-6.5 mm. When the relationship between aberrations and the pupil diameter was analyzed in a group of subjects aged 20-40 yrs, it turned out that the bigger the pupil diameter was the more statistically significant was the increase of higher order aberrations, including coma. While assessing the whole group studied we found a statistically significant reverse correlation between the pupil diameter and the subjects' age. Aberrations parameters between age groups 20-40, 40-60 and over 60 y. did not differ significantly. CONCLUSIONS: In the optical system an age-related increase of higher order aberrations is compensated by miosis, which reduces disadvantages of these aberrations and maintains the best optical quality of retinal image. PMID- 17725268 TI - [Risk factors evaluation in age- related macular degeneration]. AB - Age-related macular degeneration (AMD) is a leading cause of irreversible loss of central vision in developing countries. Study of risk factors seems to be more significant because of the lack of effective treatment. Exact recognition especially of modifiable risk factors of AMD development could increase prevention and decrease development and progression. The aim of our study was to evaluate selected modifiable and non-modifiable risk factors of AMD. The examination included 44 AMD patients and 30 healthy subjects in control group. In both groups age, sex, eye color, smoking, UV exposition, blood pressure, cholesterol level, type of diet, family history of AMD and cataract surgeries in anamnesis, were defined. The most significant risk factors of AMD development, in presented study were female gender and UV exposition. They increased a risk accordingly 1.55 and 3 times. Iris color and low vitamin and high fat intake in diet were also essential. There was no dependence on approved risk factor such smoking and AMD appearance. PMID- 17725270 TI - [Retinal capillary blood flow in exudative age-related macular degeneration]. AB - PURPOSE: The purpose of this study was to evaluate retinal capillary blood flow in patients with exudative AMD. MATERIAL AND METHODS: Twenty patients with exudative AMD and twenty four patients age-matched control subjects, were included into the study. Retinal capillary blood flow was evaluated with Heidelberg Retinal Flowmeter (HRF), measurements were taken in two macular regions. The total mean flow and mean velocity were calculated usingthe technique of automatic full field perfusion image analysis (AFFPIA). The U Mann-Whitney test was used for statistical analysis. RESULTS: Patients with exudative AMD revealed slightly lower retinal blood flow than control subjects in area I and in area II. In the AMD group total mean flow values were: 295.75 AU/ 303.85 AU, while in the control group were: 302.37 AU/ 304.42 AU. The mean velocity values were: 1.48 AU/ 1.42 AU in AMD patients and: 1.49 AU/ 1.52 AU in control group. The differences did not reach the statistical significance. CONCLUSIONS: The study results showed no changes in retinal capillary blood flow in patients with exudative AMD comparing to normal subjects. PMID- 17725269 TI - [Assessment of the macula function by static perimetry, microperimetry and rarebit perimetry in patients suffering from dry age related macular degeneration]. AB - PURPOSE: To compare the visual field results obtained by static perimetry, microperimetry and rabbit perimetry in patients suffering from dry age related macular degeneration (AMD). MATERIAL AND METHODS: Fifteen eyes with dry AMD (hard or soft macula drusen and RPE disorders) were enrolled into the study. Static perimetry was performed using M2 macula program included in Octopus 101 instrument. Microperimetry was performed using macula program (14-2 threshold, 10dB) within 10 degrees of the central visual field. The fovea program within 4 degrees was used while performing rarebit perimetry. RESULTS: The mean sensitivity was significantly lower (p<0.001) during microperimetry (13.5 dB) comparing to static perimetry (26.7 dB). The mean deviation was significantly higher (p<0.001) during microperimetry (-6.32 dB) comparing to static perimetry ( 3.11 dB). The fixation was unstable in 47% and eccentric in 40% while performing microperimetry. The median of the "mean hit rate" in rarebit perimetry was 90% (range 40-100%). The mean examination duration was 6.5 min. in static perimetry, 10.6 min. in microperimetry and 5,5 min. in rarebit perimetry (p<0.001). Sensitivity was 30%, 53% and 93% respectively. CONCLUSIONS: The visual field defects obtained by microperimetry were more pronounced than those obtained by static perimetry. Microperimetry was the most sensitive procedure although the most time-consuming. Microperimetry enables the control of the fixation position and stability, that is not possible using the remaining methods. Rarebit perimetry revealed slight reduction of the integrity of neural architecture of the retina. Microperimetry and rarebit perimetry provide more information in regard to the visual function than static perimetry, thus are the valuable method in the diagnosis of dry AMD. PMID- 17725271 TI - Macular microcirculation blood flow in patients with age related macular degeneration treated with photodynamic therapy and transpupillary thermotherapy. AB - PURPOSE: To assess the macular retinal and choroidal microcirculation blood flow in patients with exudative age related macular degeneration before and after photodynamic therapy (PDT) or transpupillary thermotherapy (TTT) with Doppler laser scanning (HRF--Heidelberg retinal flowmeter). MATERIAL AND METHODS: Thirty patients with exudative age-related macular degeneration were included in a prospective study. The diagnosis was established based on ophthalmic examination and fluorescein angiography results. In all cases the subfoveal choroidal neovascularization (CNV) was present. Control group consists of the fellow eyes with early stage of AMD (19 eyes) or with disciform scar (11 eyes). In 15 eyes with active CNV PDT was performed and in remaining 15--TTT. In all cases the macular blood flow was measured with Heidelberg retina flowmeter (HRF) before therapy and then 1 week, 4 weeks and 10-12 weeks after treatment. RESULTS: At the baseline examination in a group of eyes with active CNV the mean values of macular blood flow were significantly higher comparing to the fellow eyes and reached respectively: 678.6 +/- 125.0 AU and 298.4 +/- 79.2 AU (p=0.001). Four weeks after treatment all eyes showed the reduction of macular blood flow comparing to the baseline values (p=0.001). Ten to twelve weeks after laser therapy in all cases the increased macular blood flow was detected comparing to the previous examination (p=0.01). During the follow-up period the macular blood flow in the fellow eyes were significantly lower than in treated eyes. CONCLUSIONS: The measurement of macular blood flow using Doppler scanning laser (HRF--Heidelberg retinal flowmeter) may act as a non-invasive and useful diagnostic tool in assessment of CNV activity in patients with exudative age related degeneration before and after PDT or TTT. PMID- 17725272 TI - [Transpupillary thermotherapy in exudative age-related macular degeneration]. AB - PURPOSE: Assessment of TTT results in patients with exudative age-related macular degeneration. MATERIAL AND METHODS: The study comprised of 65 patients (73 eyes), in age 50-84 years (average age-75 yrs). The diagnosis of exudative AMD was established on the basis of fundus examination and fluorescein angiography (FA) and in some cases on indocyanine green angiography. The baseline visual acuity (VA) ranged from counting fingers at 50 cm to 0.8. In 31 (42.5%) eyes occult CNV, in 11 (15%) minimally classic CNV and in 31 (42.5%) eyes predominantly classic CNV were observed. Subfoveal CNV was present in 70 (95.9%) eyes and perifoveal in 3 (4.1%). TTT was delivered using a diode laser at 810 nm wavelength, a spot size of 1.2 to 4.5 mm and a duration of 60 seconds for each spot with power settings between 320-800 mW. Follow-up examinations were carried out every 10-12 weeks. In cases with persistent leakage from CNV in late frames of FA a retreatment was performed. The follow-up period ranged from 6 to 28 months (average - 9.8 months). RESULTS: Visual acuity improved in 22 (30.1%) eyes, stabilized in 34 (46.6%) and deteriorated in 17 (23.3%). Fluorescein angiography showed no CNV leakage in 58 (79.5%) eyes. In 56 (71.8%) with regression of leakage in fluorescein angiography improvement or stabilization of visual acuity was detected. Subretinal haemorrhages after TTT were observed in 4 eyes (5.5%). At the end of the follow-up period fibrosis of CNV was detected in 12 eyes (16.4%). CONCLUSIONS: TTT is effective and safe method of treatment of occult and classic CNV in a course of wet AMD. In a majority of cases TTT results in total or partial regression of CNV and stabilization of visual acuity. PMID- 17725273 TI - [Intravitreal bevacizumab (Avastin) iniections for neovascular age-related macular degeneration (AMD)--preliminary results]. AB - PURPOSE: To evaluate effects of intravitreal bevacizumab on visual acuity and angiographic lesions characteristics in patients with neovascular AMD and to report safety of such treatement. MATERIAL AND METHODS: 32 patients with confirmed choroidal neovascularisation (CNV) and AMD were treated. Patients received 2 intravitreal bevacizumabu (1.25 mg) iniections on 1-3 months basis. Control ophthalmic evaluations included visual acuity measurements with EDTRS charts, intraocular pressure measurements, complete ophthalmic examination in slit lamp, fluorescein angiography and blond pressure measurements. RESULTS: In 18 patients (56%) visual acuity improvement at a mean 3 lines on EDTRS charts was observed, in 9 patients (28%) visual acuity did not change and in 5 (16%) cases decreased visual acuity (about 1,5 lines in EDTRS charts) was noted. Mean follow up period was 3 months after second injection. In most study eyes fluorescein angiography revealed a marked reduction in leakage from CNV. Apart from one case with endophthalmitis symptoms after second bevacizumab injection, we did not observed systemic or ocular adverse effects of the applied treatment. CONCLUSIONS: Short-term results suggest that intravitreal bevacizumab is relatively safe form of AMD treatement and is associated with improvement in visual acuity and reduction in angiographic leakage in most patients with neovascular AMD. Further evaluation of the long-term effectiveness of this treatment is warranted. PMID- 17725274 TI - [The assessment of the correlation between vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF-alpha), interleukin 6 (IL-6), glycaemic control (HbA1c) and the development of the diabetic retinopathy in children with diabetes mellitus type 1]. AB - The aim of the work is to assess the correlation between HbA1c, VEGF, TNF-alpha, IL-6 and the development of diabetic retinopathy in children diagnosed with diabetes mellitus type 1. One hundred fourty nine children with long-standing diabetes mellitus type 1 were enrolled in the study. The patients were divided into two subgroups: children with retinopathy (Group 1; n=28) and children without retinopathy (Group 2, n=121). The control group consisted of 62 healthy children. All the examined children had VEGF, TNF-alpha and IL-6 measured in the blood serum using highly sensitive ELISA tests. Statistically significant higher blood serum levels of HbA1c, VEGF, TNF-alpha and IL-6 were found in the group 1 in comparison with the group 2. Children of the group 2 in relation to healthy controls showed statistically significant higher blood serum levels of VEGF, TNF alpha and IL-6. Elevated levels of VEGF, TNF-alpha, IL-6, HbA1c in blood serum of children with diabetes mellitus type 1 detected before development of overt signs of diabetic retinopathy might indicate the possibility of the occurrence of changes in the eye shortly. PMID- 17725275 TI - [Interleukin-12, vascular endothelial growth factor and tumor necrosis factor alpha in the process of neoangiogenesis of diabetic retinopathy in children]. AB - PURPOSE: Neoangiogenesis is a complex process, in which crucial role seems to be played by Vascular Endothelial Growth Factor (VEGF), Tumor Necrosis Factor-alpha (TNF-alpha) and Interleukin-12 (IL-12). Therefore it appeared to be worth of analysis to investigate the relation between IL-12, VEGF, TNF-alpha and the clinical course of the disease in children with Diabetes Mellitus type 1 (DM1). MATERIAL AND METHODS: One hundred and twenty six children in age 14.9+/-3.2 years diagnosed with DM1 from the Department of Paediatrics, Haematology, Oncology and Endocrinology of the Medical University of Gdansk were enrolled in the study along with 54 healthy children (as the control). All the children had their daily urine albumin secretion, HbAlc, C-peptide measured; 24 hrs blood pressure monitoring and ophthalmologic examination. Additionally, all of them had serum IL 12, VEGF, TNF-alpha measured using highly-sensitive ELISA tests (Quantikine High Sensitivity Human by R&D Systems, Minneapolis, Minn., USA). RESULTS: The children were divided into 2 groups: with retinopathy and without retinopathy. Between the groups statistically significant differences in age, duration of the disease, HbAlc serum level, C-reactive protein, daily albumin urine secretion and the systolic and diastolic blood pressure were found. Besides, statistically significant higher levels of VEGF, TNF-alpha and IL-12 were found in the group with retinopathy in comparison without retinopathy and healthy control group. CONCLUSIONS: Our results suggest that VEGF, TNF-alpha and IL-12 are engaged in neoangiogenesis regulation of diabetic retinopathy children. PMID- 17725276 TI - [The effect of the vitreal adherence in the macular region in diabetic maculopathy course based on FA picture in patients with type 2 of diabetes mellitus]. AB - PURPOSE: To evaluate the influence of local and systemic factors on diabetic maculopathy course, according to the vitreous adherence to the retina or its' lack. Ocular diabetic complications are among the most frequent causes of vision deterioration and blindness in adults in well developed countries. Diabetic maculopathy is the major condition decreasing vision in patients with type 2 of diabetes mellitus. MATERIAL AND METHODS: The study group consisted of 137 eyes in patients with type 2 of diabetes mellitus. CONCLUSIONS: All parameters analysis showed, that: better functional and anatomical results of the laser photocoagulation were achieved in PVD cases; vitreous adherence caused oedematic maculopathy persistence, in spite of properly performed laser photocoagulation; vitreo-retinal tractions presence was associated with more frequent oedematic maculopathy occurrence. PMID- 17725277 TI - [Intravitreal triamcinolone acetonide injections in treatment of cystoid macular edema due to diabetic maculopathy]. AB - PURPOSE: To appoint the most adequate follow-up parameter of intravitreal TA injections in CME treatment due to diabetic maculopathy and to find the most reliable treatment scheme. MATERIAL AND METHOD: 4 mg (in 0.1 ml) of crystalline TA were injected into the vitreous of 17 eyes. RESULTS: There was a statistically significant improvement of BCVA for distance and near vision. There was statistically significant difference in retinal thickness outcomes measured at baseline and at the end of thefollow-up by both OCT and RTA No correlation of BCVA changes and retinal thickness changes measured in OCT and RTA was found. CONCLUSIONS: Intravitreal TA administration seems to be an effective method of treatment in diabetic CME. OCT is the most adequate method of follow-up of intravitreal TA injections in treatment of CME due to diabetic maculopathy. RTA and FA changes analysis are alternative monitoring methods. Dosage of 4mg TA in 0.1 ml seems to be sufficient. In cases of CME recurrence subsequent intravitreal injection in the first 6 month after initial injection seems to unnecessary. PMID- 17725278 TI - [Inhtravitreal triamcinolone acetonide injections in the treatment of cystoid macular edema due to the central or branch retinal vein occlusion]. AB - PURPOSE: To appoint the most adequate follow-up parameter and to find the most reliable scheme of intravitreal TA injections in CME treatment in the course of CRVO and BRVO. MATERIAL AND METHODS: 18 eyes treated with intravitreal injection of 4 mg (in 0.1 ml) of crystalline TA. RESULTS: There was improvement of BCVA for distance noticed in 38.9% of eyes and for near in 44.4% of cases. There was statistically significant difference in retinal thickness outcomes measured at baseline and at the end of the follow-up by both OCT and RTA. No correlation of BCVA changes and retinal thickness changes measured in OCT and RTA was found. CONCLUSIONS: The intravitreal TA injections should be considered as an effective method. Foveal morphology and thickness analysis performed by OCT is the most adequate method in follow-up monitoring of intravitreal TA injections in CME treatment in non-ischemic CRVO or BRVO. Central retinal thickness measured by RTA and FA changes analysis are alternative monitoring methods. Dosage of 4mg TA in 0.1 ml seems to be sufficient. In cases of CME recurrence of subsequent intravitreal injection in the first 6 month after initial injection seems to be unnecessary. PMID- 17725279 TI - [An analysis of the fundus changes in families with high myopia]. AB - PURPOSE: Of this study is to present fundus changes in members of families with high myopia. MATERIAL AND METHODS: Detailed clinical examination of the enrolled subjects have been performed in the high myopia families. Both affected (presented with high myopia) and unaffected individuals (without high myopia) are given an ophthalmologic examination: best-corrected visual acuity testing, intraocular pressure examination, fundoscopy, axial length determination (using ultrasonography), refractometry. RESULTS: In the 19 high myopia families, 152 individuals were carefully examined. In 11 individuals retinal detachment have been observed. Additionally, myopic degeneration of the central retina (15 cases), degeneration of the peripherial retina (20 subjects), AMD (4 subjects), hypertrophy of the RPE (2 subjects), CNV (1 case), striae medullares (1 case) and macular foramen (1 case), have been identified. CONCLUSIONS: In the affected individuals (presented with high myopia) changes of the eye fundus and retinal detachment were more frequently observed comparing to unaffected members of the families without high myopia. In unaffected individuals genetic factor seems to play insignificant role in apperance of fundus. Changes within central retina in the high myopia individuals may conduce to severe visual impairment. PMID- 17725280 TI - [Fundus autofluorescence imaging in patients with Stargardt dystrophy and fundus flavimaculatus]. AB - PURPOSE: To identify patterns of fundus autofluorescence (AF) in patients with Stargardt dystrophy and fundus flavimaculatus. MATERIAL AND METHODS: 20 patients in age 7 to 47 years with Stargardt dystrophy and fundus flavimaculatus, were examined. Ophthalmic evaluation included nonstandarized Snellen visual acuity, complete ophthalmic examination, fluorescein angiography and color fundus photographs. The autofluorescence images were obtained using a confocal scanning laser ophthalmoscope HRA2. RESULTS: In 15 patients lack or decreased AF signal in a foveal region with punctate diffuse spots with increased and decreased AF signal extending far from the macular region were observed. In 4 patients apart from lack of the AF signal in the central area punctate spots were restricted to the macular region. In 1 patient AF image was copletely normal. CONCLUSIONS: Autofluorescence imaging allows for evaluation of the area with changes on the RPE level typical for this disease and is helpful, noninvasive examination for diagnostic process in such patients. A wide variation in clinical phenotype can occur in patients with Stargardt disease and fundus flavimaculatus. Obtained different phenotypes in autofluorescence imaging may correlate with different clinical types of this disease, described in the literature. PMID- 17725281 TI - Macular microcirculation blood flow changes after conventional surgery for rhegmatogenous retinal detachment. AB - PURPOSE: To assess the macular microcirculation blood flow in patients after conventional surgery for rhegmatogenous retinal detachment (RRD) with Doppler laser scanning (HRF--Heidelberg retinal flowmeter). MATERIAL AND METHODS: Thirty patients (13 males and 17 females) in age: 28-68 years, mean age: 58.7 years with unilateral RRD without macular involvement were included in a prospective study. According to the type of buckling procedure the patients were divided into 3 groups: I--encircling band (8 cases), II--encircling band with radial or circumferential buckling (12 cases), III--radial or circumferential buckling (10 cases). In all patients the macular blood flow was measured with Heidelberg retina flowmeter (HRF) before and 4 weeks after scleral buckling procedures. Control group consists of the fellow eyes. RESULTS: At the baseline examination in a group of eyes with RRD the mean values of macular blood flow were significantly lower comparing to fellow eyes and reached respectively: 298.4 +/- 79.2 AU and 435.6 +/- 121.0 AU (p=0.001) and correlated with the extent of RRD (p<0.05). Four weeks after surgery eyes that underwent the buckling procedures showed the elevation of macular blood flow as compared to the baseline values (p=0.001), however they remain slightly lower as compared to fellow eyes. The macular microcirculation blood flow changes were not influenced by the type of scleral buckling (p=0.2). CONCLUSIONS: In the eyes with rhegmatogenous retinal detachment without macular involvement the mean macular microcirculation blood flows were lower as compared to fellow eyes. Different buckling procedures for rhegmatogenous retinal detachment influence the macular blood flow, causing its improvement as compared to the preoperative status but they remain lower comparing to fellow eyes. PMID- 17725282 TI - Assessment of blood flow velocity in eyeball arteries in multiple sclerosis patients with past retrobulbar optic neuritis in color Doppler ultrasonography. AB - PURPOSE: The aim of the study was to evaluate blood flow velocity in eyeball arteries in affected and unaffected eyes in patients with past retrobulbar optic neuritis in the course of multiple sclerosis (MS). MATERIAL AND METHODS: Evaluation of blood flow velocity in 16 eyes of 16 patients with unilateral retrobulbar optic neuritis was performed in ophthalmic artery (OA), central retinal artery (CRA) and short posterior ciliary artery (SPCA). In the arteries the following parameters have been assessed: peak systolic velocity (PSV), end diastolic velocity (EDV), mean flow velocity (MV), indicators of peripheral vascular resistance such as Gosling Index (PI) and Pourcelot Index (RI). The obtained values have been compared to values of blood flow in the same arteries of the control group. Using Shapiro-Wilk test, mode of distribution of each parameter was analyzed. The statistic analysis has been done between group of affected eyeballs (group 1) and control group and between group of unaffected eyeballs (group 2) in multiple sclerosis patients and control group (13 individual, 26 eyes), regarding the age. The assessment was performed with the assistance of t-Student test, and in case of lack of normal distribution, by U Mann-Whitney test. Statistically significant difference was established when p value was below 0.05 (p < or = 0.05). RESULTS: Among the analyzed parameters of blood flow velocity, statistically significant disturbances in the examined eyeball arteries were found. The most significant disturbances of blood flow were found in CRA and SPCA. The affected parameters were: diminished MV velocity in OA; PSV, MV, RI in CRA and PSV, EDV, MV and RI indices in SPCA. The similar blood flow velocity disturbances were also found in unaffected eyeball arteries. CONCLUSIONS: In MS patients with past optic neuritis disturbances of ocular circulation can be observed. The statistically significant diminishing blood flow velocity parameters and vascular resistance indices in eyeball arteries may indicate alterations of blood flow. Lowering of systolic and mean velocities and resistance indices of blood flow are most expressed in CRA and SPCA. Reduction in blood flow parameters in the examined arteries occur both, in the eyes previously affected by past optic neuritis and in contra lateral, unaffected eyes. PMID- 17725283 TI - [An application of Color Doppler ultrasonography in evaluate of brachytherapy in patients with uveal melanomas]. AB - Uveal melanomas, even those of big size, are recently more readily treated conservatively, with radiotherapy, though the efficiency of this treatment has not been yet established. PURPOSE: Of the study was the assessment of the usefulness of Color Doppler (CD) or Power Doppler (PD) examination in monitoring the effectiveness of brachytherapy in the management of melanomas. MATERIAL AND METHODS: Examination was performed in 15 patients, who were treated because of medium size or large uveal melanomas, with plaque radiation (brachytherapy). CD/PD examination of blood flow within the tumor, with the use of SonoVue contrast agent in several cases, was performed before institution of the therapy and two times after the treatment, as follow-up. RESULTS: Regression of the tumor and gradual atrophy of its neovascularisation was observed in all the examined patients. The enhancement of Color Doppler imaging with contrast agent helps in making decision to further therapeutic options as complex situation. CONCLUSIONS: Color and Power Doppler ultrasonography is a helpful method in monitoring the effectiveness of brachytherapy in patients with uveal melanomas. PMID- 17725285 TI - [Outcome of cataract surgery in patients with pigmentary retinal degeneration]. AB - PURPOSE: To evaluate the results of cataract surgery in patients with RP because retinitis pigmentosa is one of the disease entities that belongs to tapeto retinal degenerations. The occurrence of RP appearance is 1:4000 to 1:3000. MATERIAL AND METHODS: Twenty patients with RP (7 women and 13 men, 33 eyes), who underwent cataract surgery were examined retrospectively. Average age in our group was 46.6 years. Visual acuity, intraocular pressure, slip lamp examination, fundus examination, cataract morphology, visual field were taken before surgery and on discharge, on the basis of medical documentation. Control examination was taken, on average, eighty one months after cataract surgery. Nine eyes were operated by phacoemulsification, 24 eyes by means of extracapsular cataract extraction. In the same way control group of 18 patients who underwent cataract surgery without RP (33 eyes) was examined. RESULTS: In RP group in 63.6% patients on discharge from the hospital and in 60.6% patients during the control examination, improvement of visual acuity was revealed. Deterioration was noted in 18.2% of patients on discharge from hospital and in 24.2% of patients during the control examination. In the control group improvement of visual acuity was revealed in 90.9% of patients on discharge and in 97% patients during the control examination, whereas deterioration of visual acuity occurred in 6.1% patients on discharge and in 3% patients during the check examination. CONCLUSIONS: In patients with retinitis pigmentosa cataract occurs earlier then in the control group. Cataract surgery for relatively minor opacities is beneficial in patients with RP, and causes improvement of visual acuity in most of eyes undergoing surgery. PMID- 17725284 TI - [Phacofragmentation with perfluorocarbon liquid and anterior chamber or scleral fixated intraocular lens implantation for the management of luxated crystalline lenses--long-term results]. AB - PURPOSE: Estimation of long-term results and complications of complex surgical technique, used for the management of luxated crystalline lenses. MATERIAL AND METHODS: This prospective study involved 29 consecutive patients (31 eyes) with the mean age of 62 years. The applied surgical technique comprised pars plana vitrectomy, perfluorocarbon liquid injection and crystalline lens phacofragmentation in the vitreous cavity. Simultaneously, anterior chamber intraocular lenses (IOLs) were implanted in 13 eyes, and scleral-fixated, posterior chamber IOLs in 17 eyes. In one patient with high myopia the lens was not implanted. The follow-up ranged between 9 and 38 months (mean 22.8 months). RESULTS: No complications were observed during phacofragmentation. Improvement in visual acuity was achieved in 18 cases one week after operation and in 23 patients at last examination. We achieved visual acuity of 4/50--hand movements in 4 cases, 5/16-5/50 in 3 eyes, 5/8-5/12 in 7 and 5/5-5/7 in 17 cases, in last examination. There were no intra-operative complications. Low visual acuity in some cases was due to the presence of postoperative complications or coexisting eye diseases, such as secondary glaucoma, atonic pupil, age related macular degeneration, retinal detachment and macular hole. CONCLUSIONS: Phacofragmentation with perfluorocarbon liquid and IOL implantation for the management of luxated crystalline lenses is safe and effective method, providing very good long-term functional results. PMID- 17725286 TI - [Effect of mydriasis and accommodation on intraocular pressure and pigment release in patients with the pigment dispersion syndrome]. AB - PURPOSE: To determine if mydriasis and accommodation affect intraocular pressure (IOP) and pigment release in patients with the pigment dispersion syndrome (PDS). MATERIAL AND METHODS: Seventeen patients (34 eyes) diagnosed with PDS were included in the study (10 men and 7 women). Tonometry was performed on all patients before, and at 1 and 2 hours after mydriasis and before, and at 1 and 2 hours after sustained reading. The statistical analysis was performed using the paired T-test. RESULTS: In both tests the differences in intraocular pressure values were not statistically significant. Pigment liberation occurred in 11.8% of patients after mydriasis but was not associated with an increase in IOP. CONCLUSION: Accommodation during sustained reading did not cause significant pigment release or an IOP rise. PMID- 17725287 TI - [Strabismus surgery after macular translocation]. AB - PURPOSE: To present the application of various extraocular muscle surgery techniques to eliminate incyclotorsion induced by macular translocation. MATERIAL AND METHODS: Authors present surgical options and present the case of the patient in whom macular translocation was performed in Tubingen (Germany). Afterwards five strabismological surgeries were done: 2 in Tubingen and 3 in Department of Strabismology, Cracow District Eye Hospital. RESULTS: At the end of strabismological treatment the patient was free of disabling image tilt and diplopia. CONCLUSIONS: We present this case as an announcement of future challenge for strabologists if macular translocation surgeries will be performed in Poland. PMID- 17725288 TI - [Diagnostic difficulties in patients with macular lesions]. AB - We present diagnostic difficulties associated with macular lesions giving symptoms of central visual field distortions due to retinal and choroidal diseases different than age related macular degeneration (AMD). AIM: To analyze causes of metamorphopsia similar to that occurring in AMD. MATERIAL AND METHODS: Patients presented for Preferential Hyperacuity Perimetry (PHP) examination due to the central visual field distortion. In cases of abnormal PHP result, we performed visual acuity testing and stereoscopic examination of the eye fundus. In selected cases optical coherence tomography (OCT), fluorescein angiography (FA) and indocyanine green chorioangiography (ICG) were performed. Following these examinations the decision about further management was made. Analyzed cases demonstrate the need to correlate the PHP examination, which objectifies visual field distortions symptoms with stereoscopic eye fundus examination and additional examinations of retina and choroid including OCT, FA and ICG. PMID- 17725289 TI - [Complex diagnosis of the early macular changes due to AMD]. AB - We demonstrated diagnostic cases of the early macular changes due to AMD, which caused central visual field disturbances. The aim of the study was to systemize the management in patients with macular lesions due to the age related macular degeneration, frequency determination and statement of the performed additional tests range. Patients reported central visual field distortions. We performed visual acuity testing, stereoscopic eye fundus examination, and PHP (macular visual field testing), which objectified distortions symptoms. Based on that tests and fellow eye condition, decision about OCT and FA and ICG performance were made. Further management was determined according to the results of that examinations: follow-up with vitamins and microelements supplementation or PDT. Our analysis confirm, that to monitor early macular changes due to AMD, follow-up examinations in 2-3 months interval are indicated: visual acuity testing, stereoscopic eye fundus examination and macular lesions modeling in PHP In difficult cases or in more advanced lesions FA, OCT and ICG were performed. PMID- 17725290 TI - Acute retinal pigment epithelitis in 18 years old patient. AB - We report case of acute retinal pigment epithelitis (ARPE), a very rare ophthalmic disorder, which has a very good final visual prognosis. The 18 years old woman was examined by ophthalmologist for sudden visual decrease of vision and dark spot in visual field of her left eye. The best corrected visual acuity (BCVA) of the left eye at the initial diagnosis was 0.1 and after 4 months improved to 0.9. The diagnosis or ARPE was made on the basis of fundoscopy, fluorescein angiography, electroretinography and optical coherence tomography (OCT) examination. PMID- 17725291 TI - [Diffuse atrophy of the choroid--a case report]. AB - PURPOSE: The authors present a case of the 66-year-old female patient suffering from the diffuse atrophy of the choroid. MATERIAL AND METHODS: The 66-year-old woman was referred to the Ophthalmological Clinic in Krakow with the diagnosis of choroideremia. The patient developed central vision problems (mainly in the left eye) and night blindness. We performed following investigations: distance and near visual acuity with Snellen charts, Amsler grid test, the investigation of the anterior and posterior segments of both eyes, and the fluorescein angiography as well as the infrared photo of the fundus. The assessment of ornithine serum level was performed. RESULTS: The ophthalmological examination revealed: the distance visual acuity in the RE=0.5, and in the LE=0.25. The near visual acuity in the RE=0.5, in the LE=0.75. The Amsler grid test in the RE showed no pathology but in the LE revealed in the nasal aspect of the central visual field a relative scotoma. Fundoscopy, fluorescein angiography and infrared imaging revealed the broad patch form atrophy of the RPE and choriocapillaris within the whole fundus and also within the macula. The serum level of ornithine was within the normal limits. CONCLUSIONS: Based on the results of performed investigations the definitive diagnosis of a very rare dystrophy--a diffuse atrophy of the choroid was established. PMID- 17725292 TI - [Posterior staphyloma in the normal lenght eyeball--a case report]. AB - PURPOSE: The aim of the study is to present a case of posterior staphyloma in the eyeball of the normal length. METHODS AND RESULTS: A 17-year-old boy underwent full ophthalmologic examination due to impaired vision in the right eye (R.E.) lasting for one month. The visual acuity of R.E. and L.E. was found to be 0.8 and 1.0, respectively; near visual acuity for both eyes--0.5, intraocular pressure in both eyes--16 mmHg. The anterior part of both eyes was normal. The R.E. ophthalmoscopy revealed the presence of posterior staphyloma near the temporal upper optic disc margin accompanied by serous retinal detachment above the macula. The L.E. ophthalmoscopy--normal. The eyeball length 23 mm and posterior staphyloma depth 2.4 mm. Refraction test--normal without any vision defect. Additionally fluorescein angiography, US B and OCT confirmed the presence of posterior staphyloma of the right eye. During the 3-month follow up the retinal detachment markedly decreased. CONCLUSIONS: The case report shown that posterior staphyloma may develop in the eyeball of normal length although its incidence is rare. New diagnostic methods, especially OCT, are very helpful in the clinical picture evaluation. PMID- 17725293 TI - [Disadvantageous course of ophthalmological changes in young women with long lasting diabetes mellitus followed by the symptoms of anorexia nervosa]. AB - PURPOSE: To present the course and progression of very severe proliferative retinopathy in young women with long lasting diabetes mellitus and symptoms of anorexia nervosa. MATERIAL AND METHODS: The data of 5 young women, in age 25-32 years, suffering from diabetes mellitus 15 to 29 years with intended weight lose. The progression of ophthalmological changes was observed, followed by considerable fluctuations of glucose blood. RESULTS: In the time of weight lose in all patients, the worsening of the visual acuity was observed and it was the first reason for ophthalmological check-up. The initial best corrected visual acuity was 0.1-0.9. The rubeosis of the iris, cataracts and proliferative retinopathy with intravitreal hemorrhage and tractional retinal detachment were observed. Despite the immediate ophthalmological treatment (lasertherapy, pars plana vitrectomy, criopexy and retinopexy) the useful visual acuity (>0.1) was maintained only in one eye. CONCLUSIONS: 1. In case of significant exacerbation of progression of ophthalmological changes in patients with long lasting diabetes mellitus and anorexia nervosa the monitoring of their psychological and physical conditions is essential. 2. In the case of weight lose in patients with long lasting diabetes mellitus the rigorous ophtalmological monthly consultations are obligate. PMID- 17725294 TI - [Perforating eye injury with retained inorganic intraorbital foreign body--case report]. AB - Authors would like to present a case of perforating eye injury with inorganic foreign body, which consequently stick behind the globe in muscular cone space. We discuss visual prognosis after injury which depends on injury mechanism, wound extension and localization as well as tolerance of intraorbital foreign body through eye's tissue and prevention of eye injuries. We would like to stress the necessity of meticulous primary microsurgical repair and possible secondary surgical reparation to reduce posttraumatic visual loss. There is also a possibility of late complication due to vitreoretinal proliferation as a consequence of healing process. PMID- 17725295 TI - [Retinal pigmentary degeneration--clinical features, diagnostics and possibilities of treatment]. AB - The purpose of this study was to evaluate clinical course of retinitis pigmentosa taking into consideration models of inheritance and possible treatment. Retinitis pigmentosa belongs to heterogeneous group of hereditary disorders, which are connected with gradual loss of the photoreceptor function, firstly rod cells subsequently cones, which is accompanied by the retinal pigmentary epithelium disorder. Retinitis pigmentosa connected with X chromosome is one of the most severe form of this disease that in polish population takes place with frequency at average 10-15% which is similar to ADRP--10-20%. Course of RP, despite many similarities may differ from each other and prognosis depends on model of inheritance. Unfortunately, in spite of many efforts, nowadays medicine do not have successful treatment for patients with RP. PMID- 17725296 TI - [Comparative analysis of proteins in seminal plasma of non-obstructive azoospermia patients and healthy fertile males]. AB - OBJECTIVE: To analyse protein alterations in the seminal plasma of non obstructive azoospermia patients. METHODS: Semen samples were collected from 11 healthy fertile and 6 azoospermia male volunteers respectively and tested by SELDI-TOF-MS with CM10 protein chip to get protein spectra maps, which were automatically treated with the special softwares of Ciphergen Inc. RESULTS: The mean peak heights of 28 proteins expressed in the seminal plasma of the azoospermia patients were statistically different from those of the healthy fertile males (P < 0.05 ), of which 24 were of lower contents than in the normal controls, 4 with remarkably significant difference, M/Z 7 196.058, 7 630.573, 7 547.610 and 7 709.833 (P < 0.01). CONCLUSION: The seminal plasma proteins of the azoospermia patients were significantly different from those of the healthy fertile males, with decreased contents of most of the different proteins, which might be significantly correlated with the development of azoospermia. PMID- 17725297 TI - [A preliminary study of contrast-enhanced ultrasound in benign prostatic hyperplasia]. AB - OBJECTIVE: To analyze and evaluate the characteristics of benign prostatic hyperplasia (BPH) on contrast-enhanced ultrasound. METHODS: Forty-eight BPH patients confirmed by transrectal ultrasound-guided biopsy underwent contrast enhanced ultrasound. Contrast pulse sequencing technique (CPS) and quantitative software-ACQ were used, and the parameters of beginning enhancement time, disappearing and transit time and peak intensity (PI) of the inner gland and outer gland were recorded and analyzed. RESULTS: The prostate was rich with blood and enhanced significantly on contrast-enhanced ultrasound. The beginning enhancement time of the prostatic inner gland, especially the area around the urethra, was much earlier than that of the outer gland, (26.68 +/- 3.76) and (31.24 +/- 5.33) s, respectively (P = 0.000). The contrast disappeared later in the inner gland than in the outer gland, (200.68 +/- 59.40) and (157.56 +/- 50.66) s, respectively (P = 0.000). The transit time of the contrast in the inner gland was much longer than in the outer gland, (173.94 +/- 60.14) and (129.21 +/- 56.91) s, respectively (P = 0.000). PI of the inner gland was much higher than that of the outer gland, (90.45 +/- 42.19) and (65.32 +/- 25.15) dB, respectively (P = 0.000). CONCLUSION: Contrast-enhanced ultrasound makes it possible to continuously observe the blood perfusion process of BPH, and promises to be an effective means for observing the blood supply in BPH. PMID- 17725298 TI - [Fenvalerate affects sperm motility in SD rats]. AB - OBJECTIVE: To observe the direct effects of fenvalerate (Fen) on sperm motility in SD rats. METHODS: Sperm were isolated from caudal epididymides of healthy adult male rats with the diffusion method. The motility parameters of the isolated sperm, such as VCL, VSL, VAP, BCF, STR and LIN, were monitored by computer-assisted sperm analysis (CASA) system after 1, 2 and 4 h Fen-exposure in vitro at concentrations of 0, 1, 4, 16 and 64 micromol/L respectively. RESULTS: After 1 and 2 h Fen-exposure, VSL, BCF, STR and LIN decreased significantly at 64 micromol/L compared with the control group. After 4 h Fen-exposure, the motility parameters VCL, VSL, BCF, STR and LIN dropped progressively at 64 micromol/L, and VCL declined markedly at 16 micromol/L. However, only VCL and STR showed alterations in a time-response manner. CONCLUSION: Fen may affect the caudal epididymal sperm and produce a direct toxic effect on sperm motility in SD rats. PMID- 17725299 TI - [Resveratrol helps restore spermatogenesis after testis injury induced by 2,5 hexanedione]. AB - OBJECTIVE: To study the effect of resveratrol on spermatogenesis after 2,5 hexanedione(2,5-HD)-induced testicular injury. METHODS: Forty male SD rats were randomly divided into 5 groups. Group A were normally raised and Group B, C, D and E exposed to 1% 2,5-HD for 5 weeks, followed by administration of resveratrol of different concentrations (20, 40 and 80 mg/[ kg x d], respectively) to Group C, D and E for 9 weeks. Then the rats were killed, their physical signs, body weight gain and testis weight were assessed, and immunohistochemistry and Western blot analysis used to investigate the numbers and diameters of seminiferous tubules and the expression of c-kit protein of spermatogenic cell membrane. RESULTS: The rats exposed to 2,5-HD showed weak body, lax skin, dim color pattern, tardy body weight gain, and emaciated testis. Immunohistochemistry revealed emaciated seminiferous tubules, stagnant obsolete spermatogonia and negative expression of c-kit protein. After resveratrol administration, the 2,5 HD-induced physical signs were improved and close to normal. Compared with those of the 2,5-HD injured group, the body weight and testis weight of the resveratrol treated group increased obviously (P < 0.01); and the aliquots of the seminiferous epithelia began to differentiate and the spermatogenesis and expression of c-kit protein partly resumed (P < 0.01). With increasing dose of resveratrol, the diameters and numbers of seminiferous tubules (P < 0.01) and the expression levels of c-kit protein (P < 0.01) were gradually and significantly restored almost to normal. CONCLUSION: Resveratrol could promote the recovery of spermatogenesis after 2,5-HD-induced testicular injury. PMID- 17725300 TI - [Concentration of seminal plasma and serum inhibin B: a predictor in the diagnosis of azoospermia]. AB - OBJECTIVE: To evaluate the concentrations of seminal plasma and serum inhibin B in the differential diagnosis of obstructive and non-obstructive azoospermia. METHODS: We included 37 infertile men with obstructive azoospermia, another 33 with non-obstructive azoospermia and 25 normal fertile men as controls, and measured the concentrations of their FSH serum, seminal plasma and serum inhibin B, using Testicular Histology Johnson Score for the azoospermia infertile men. RESULTS: The concentration ratio of seminal plasma to serum inhibin B was 2.17 in the control and 3.63 in the non-obstructive azoospermia group, with no significant difference (P = 0.29) in between, but obviously lower in the obstructive azoospermia group (0.18), significantly different from the above two (P < 0.01). CONCLUSION: The concentration ratio of seminal plasma to serum inhibin B can be used as a predictor in the diagnosis of obstructive and non obstructive azoospermia. PMID- 17725301 TI - [Screening and characterization of human phage Fab antibody gene to prostate specific membrane antigen]. AB - OBJECTIVE: To screen and characterize the variable region gene about prostate specific membrane antigen (PSMA) of the Chinese Fab fragment, and to establish a new approach to researches on PSMA and prostate gene therapy. METHODS: We used purified PSMA protein as antigen, stuck it on the ELISA plate and scanned the phage Fab fragment antibody library by phage display technology. After five cycles of "absorbing-elution-amplification", we got the Fab fragment phage antibody of PSMA with high antigen binding ability and specificity, and tested it with immunodetection and sequencing. RESULTS: The sequence of Fd fragment was 696 base pairs encoding 232 amino-acid residues, with 98% homological similarity to the human immunoglobulin gamma chain, while the light chain was constructed by 630 base pairs encoding 210 amino-acid residues, with 93% homological similarity to kappa chain. CONCLUSION: Using phage display technology, we obtained the gene sequence of Fab antibody fragment specific to PSMA, and the antibody gene has the classic structural features of immunoglobulin light chain and heavy chain. The coding output of the antibody gene has the specificity and immunological competence to PSMA. PMID- 17725302 TI - [Diffusion weighted imaging: its diagnostic and differential value for prostate cancer]. AB - OBJECTIVE: To explore the diagnostic and differential value of diffusion weighted imaging (DWI) for prostate cancer. METHODS: Included in the study were 50 patients with prostatic diseases, including 19 cases of prostate cancer (PCa) and 31 cases of benign prostatic hyperplasia (BPH), and another 16 healthy volunteers were recruited as controls. All underwent DWI sequence on a 1.5T superconducting MRI system with an endorectal coil. The results from DWIs and apparent diffusion coefficient (ADC) maps were treated statistically. RESULTS: The mean ADC value of the prostatic peripheral zone and the prostatic central gland of the 16 healthy volunteers were (170.23 +/- 37.39) x 10(-5) mm2/s and (127.84 +/- 17.93) x 10(-5) mm2/s, while those of the 31 BPH cases and 19 PCa cases were (175.21 +/- 64.86) x 10(-5) mm2/s and (104.23 +/- 26.15) x 10(-5) mm2/s, respectively. There were significant differences in the tissue types between any two groups after the treatment of one-way ANOVA, except between the groups of the peripheral zone and. BPH. CONCLUSION: PCa shows specific DWI features that could be distinguished from those of the normal prostatic tissues and BPH. Therefore, DWI has an important clinical application value in the diagnosis and differentiation of PCa. PMID- 17725303 TI - [A clinical study of sertraline and vardenafil in the treatment of premature ejaculation complicated by erectile dysfunction]. AB - OBJECTIVE: To evaluate the efficacy and safety of sertraline and vardenafil in the treatment of patients with concomitant erectile dysfunction (ED) and premature ejaculation (PE). METHODS: Sixty patients with concomitant ED and PE received at our clinic of andrology were randomly divided into a vardenafil group and a sertraline group. The vardenafil group received flexible doses of vardenafil from 10 mg to 20 mg and the sertraline group 50 mg daily, both for 2 months. The differences in IIEF-5 before and after the treatment were recorded and compared, and the results of ED treatment evaluated. Intravaginal ejaculatory latency time (IELT) was recorded to evaluate the outcome of PE treatment. RESULTS: In the vardenafil group, 24 patients had their ED improved and the efficacy rate was 80%, as compared with 27% in the sertraline group. There was significant difference between the two groups (P < 0.05). Twenty patients had their PE improved in vardenafil group, with an efficacy rate of 67% as compared with 40% in the sertraline group. The difference was significant between the two groups (P < 0.05). In both of the two groups, a significantly higher rate of PE improvement was found in patients with improved ED than in those without. Only mild side effects were recorded, and none withdrew from the treatment. CONCLUSION: To patients with concomitant ED and PE, the key to the treatment is to improve their erectile function, and for this purpose, vardenafil works better than sertraline. PMID- 17725304 TI - [Predictive factors for conversion of transurethral resection of the prostate to open prostatectomy]. AB - OBJECTIVE: To evaluate the factors for the conversion of transurethral resection of the prostate (TURP) to open prostatectomy and to provide clinical evidence for surgical options. METHODS: From January 1997 to March 2005, we performed 1 086 TURP and made retrospective analyses of 11 risk factors concerning the demographics, clinical history, laboratory data, ultrasound results, and intraoperative complications of the patients. In addition, multivariate logistic regression was used to determine those variables predicting the conversion of TURP. RESULTS: Thirty-nine (3.59%) of the TURP cases required conversion, mostly because of uncontrollable hemorrhage (71.79%). Multivariate analyses showed that a prostate volume > 85.2 ml (OR = 2.568, P < 0.01), intraoperative slit of capsula prostatic (OR = 1.916, P < 0.01) and a second midstream bladder specimen (VB2) white blood cell count of the urine > 13.5/HP (OR = 1.486, P < 0.01) predicted the conversion to open prostatectomy. CONCLUSION: Benign prostatic hyperplasia (BPH) patients with a huge prostate and those with intraoperative slit of capsula prostatic undergoing TURP are more likely to be converted. And uncontrollable hemorrhage, huge prostate and poor endoscopic vision are the major reasons for the conversion. PMID- 17725305 TI - [Adult prostate sarcoma: a report of 6 cases with clinical analysis]. AB - OBJECTIVE: To investigate the diagnosis, treatment and prognosis of sarcoma of the adult prostate. METHODS: We reported 6 cases of sarcoma of the adult prostate, of which 3 were leiomyosarcoma, 2 rhabdomyosarcoma and 1 malignant neurilemoma, 2 at Ghavimi Stage II, 3 at Stage III and 1 at Stage IV. The patients were aged from 18 to 44 years (mean 31 years) and their disease course ranged from 3 to 12 months (mean 7 months). Five of them received operation, radiotherapy and / or chemotherapy and 1 underwent cystostomy only. RESULTS: Immunohistochemical dyeing showed vimentin to be positive while PSA and PAP negative in all the 6 cases, actin (HHF35) positive in the cases of leiomyosarcoma and rhabdomyosarcoma, and S-100 and lysozyme positive in the case of malignant neurilemoma. One case failed to be followed up, and the other 5 died 2-11 months after the operation. CONCLUSION: Sarcoma of the adult prostate initiates with the symptom of progressive dysuria, which can be diagnosed by DRE test and confirmed by needle biopsy. Early diagnosis and radical surgical resection may offer the best chance of survival, but with poor prognosis. PMID- 17725307 TI - [Prenatal diagnosis of two pregnancies with risk of chromosomal disorders]. AB - OBJECTIVE: To report the prenatal diagnosis of 2 cases of pregnancy with the risk of chromosomal disorders. In Case 1, the pregnant woman had a daughter with testicular regression syndrome and a segmental duplication of Ypter --> Yp11.2 and a deletion of Yq11.23 --> Yqter. In Case 2, both the pregnant woman and her husband were carriers of chromosomal balanced translocation. METHODS: Two samples of amniotic fluid were obtained at the 19th week of gestation for fetal karyotype analysis. For Case 1, FISH with a probe of Xp/Yp subtelomere was performed on the metaphase of the amniotic fluid, genomic DNA of the amniotic fluid extracted and multiplex PCR conducted for AZF regions. Both the pregnant women underwent sonography to confirm the karyotypic diagnosis. RESULTS: Cytogenetic, FISH and multiplex PCR analysis of the cultured amniotic fluid cells from Case 1 showed a normal male karyotype, and ultrasound scan of the fetus showed normal male external genitalia and normal development. Cytogenetic analysis of the cultured amniotic fluid cells from Case 2 revealed a karyotype of balanced translocation with t(13 ; 14) from the father, and no abnormality of the fetus was found by ultrasound scan. CONCLUSION: It is helpful to perform cytogenetical and molecular prenatal diagnosis in combination with ultrasound scan for the fetus with the risk of chromosomal disorders and subsequently for genetic counseling. PMID- 17725306 TI - [Effects of 40H-tamoxifen on the proliferation and apoptosis of prostate stromal cells]. AB - OBJECTIVE: To investigate the effects of 4OH-Tamoxifen (OHT) on proliferation and apoptosis of primary cultured prostate stromal cells. METHODS: Primarily cultured prostate stromal cells in vitro were treated with various concentrations (10(-8) mol/L - 10(-5) mol/L) of estradiol (E2), diethylstilbestrol (DES), OHT and the mixture of E2 (10(-8) mol/L - 10(-6) mol/L) with OHT (10(-7) mol/L) and then MTT and TUNEL were used to detect their proliferation and apoptosis respectively. RESULTS: There was a significant difference (P < 0.05) between OHT and estrogens in the effects on the apoptosis and proliferation of the primarily cultured prostate stromal cells. OHT suppressed proliferation of the prostate stromal cells at the concentrations from 10(-7) mol/L to 10(-5) mol/L (P < 0.05), and this effect was concentration related (r = -0.383, P = 0.005); OHT (10(-7) mol/L) suppressed the proliferation stimulation effect of E2 at the concentrations from 10(-8) mol/L to 10(-6) mol/L (P < 0.05). OHT induced apoptosis at the concentrations from 10(-8) mol/L to 10(-5) mol/L (P < 0.05), and this effect was concentration related (r = 0.349, P = 0.012). The apoptosis induced by OHT could not be reversed by E2 at the concentrations from 10(-8) mol/L to 10(-5) mol/L (P > 0.05). CONCLUSION: OHT can obviously suppressed the proliferation and promote the apoptosis of primarily cultured prostate stromal cells, which might not be totally attributed to the competitive inhibition of the estrogen receptor. PMID- 17725308 TI - [Analysis of detection and antimicrobial resistance of pathogens in prostatic secretion from 1186 infertile men with chronic prostatitis]. AB - OBJECTIVE: To investigate the distribution and the antimicrobial resistance of the bacteria, mycoplasma and Chlamydia trachomatis isolated from the prostatic secretion of infertile men with chronic prostatitis, and to provide clinicians with grounds for choosing antibiotic agents. METHODS: The bacteria obtained were isolated and identified, the Chlamydia trachomatis was detected by FLO-PCR, and the results were analysed statistically. RESULTS: In 1 186 specimens of EPS, the total positive rate of isolates was 51.7%. Among them, there were 364 strains of gram-positive coccus, 20 gram-negative bacillus, 5 other strains and 157 mycoplasma, including 116 Ureaplasma urealyticum and 41 Mycoplasma hominis, and 67 Chlamydia trachomatis DNA. As for the isolated staphylococci, their antimicrobial resistance was the lowest against vancomycin (0.0%), but the highest against penicillins (76.9%-100%); for the Streptococcus agalactiae, it was the highest against erythromycin and clindamycin (100%), and the lowest against beta-lactams, aminoglycosides, trimethoprim + sulfamethoxazole, rifampin and vancomycin (0.0%); for the Ureaplasma urealyticum, it was the highest against ciprofloxacin (59.5%), and the lowest against josamycin, tetracycline and fosfomycin (1.7%); for the Mycoplasma hominis, it was the highest against erythromycin (100%), and the lowest against doxycycline and fosfomycin (0.0%). CONCLUSION: Bacteria, mycoplasma and Chlamydia trachomatis are the possible etiological factors of male infertility. Isolated bacterial strains differ greatly in their resistance against different antibiotics. PMID- 17725309 TI - [Update of the relationship between erectile dysfunction and endothelial function]. AB - Endothelial function plays a very important role in the process of erection. Erectile dysfunction (ED) and coronary artery disease (CAD) overlap in risk factors, aetiology and clinical outcomes. Endothelial dysfunction is considered to be their shared aetiological factor. There is growing evidence that patients presenting with ED should be investigated for CAD, even if with no symptoms of the problem. Earlier diagnosis of ED can facilitate prompt intervention, reduce long-term complications, especially the risk of CAD, and provide effective treatment for ED. PMID- 17725310 TI - [The role of seminal vesicles in male fertility]. AB - Seminal vesical secretion is important for male fertility. It affects semen coagulation, sperm motility, stability of sperm chromatin and suppression of the immune activity in the female reproductive tract. PMID- 17725311 TI - [Correlation of testis/sperm specific thioredoxin-1, 2 and 3 with male reproduction]. AB - Sptrx-1, 2 and 3 are a series of thioredoxins specifically expressed in the testis/sperm. They play a significant role structurally and functionally in the process of spermiogenesis. The genesis and mutation of sptrx-1, 2 and 3 are correlated to male reproduction. Taking sptrx-1, 2 and 3 as the target of study and treatment will open up a new field in the clinical study of male reproduction. PMID- 17725312 TI - [Animal models in sexual dysfunction]. AB - Animal models in sexual dysfunction were reviewed to further improve the modeling methods and to promote the effectiveness of drug evaluation translation from animal models to humans. A MEDLINE search was performed to retrieve articles relating to animal models in sexual dysfunction. Researches on a variety of animal models in sexual dysfunction, with their own merits, has to a certain extent contributed to the understanding of sexual function. However, no models could give a fully accurate assessment of sexual function. The existing sexual function studies on animal models of interpretive function, the development mechanisms, the effects of drugs on sexual function and the clinical translation still have some deficiencies, but with their basic principles and ideas for the improvement of the models and the preservation of the valuable data of drugs and clinical trials. PMID- 17725313 TI - [Advances in the treatment of male acquired urinary incontinence]. AB - Male acquired urinary incontinence can be a complication of radical prostatectomy and posterior urethroplasty. Mild urinary incontinence can be improved by pelvic floor exercises, biofeedback and medicine treatment. Severe urinary incontinence requires more active treatment, such as injection therapy, artificial urethral sphincter insertion, and bulbourethral sling. Recent progress in the treatment of male acquired urinary incontinence is reviewed in this article. PMID- 17725314 TI - [Shengli capsules enhance sexual ability in male rats]. AB - OBJECTIVE: To evaluate the effects of Shengli capsules on the sexual ability of normal and castrated male rats. METHODS: Shengli capsules were given by intragastric administration to 100 experimental male rats at different doses of 0.35, 0.70 and 1.40 g / kg. Data were collected and analyzed, including capture latency period, times of capture, sexual endurance and times of ejaculation, to assess the effects of Shengli capsules on the sexual ability of the rats. The Castrated Animal Impotence Model was employed to determine the erectile latency period and the function parameters of the preputial gland, seminal vesicle and prostate, so as to test the effects of Shengli on the development of the rats'sexual organs. RESULTS: Shengli was proved to be effective in shortening copulation latency in the dose groups of 0.35, 0.70 and 1.40 g / kg (P < 0.01), increasing significantly the frequency of capture in the high- and low-dose groups of 0.35 and 1.40 g / kg (P < 0.05), reducing the latency period to erection in the low-dose group of 0.35 g / kg, and blocking the shrink of the seminal vesicle and prostate in the medium-dose group of 0.70 g / kg. CONCLUSION: Shengli is significantly effective in enhancing the sexual ability of male rats: it can boost libido, increase erection frequency and improve sexual performance. However, further studies have yet to be done on its action mechanisms. PMID- 17725315 TI - Impact of noncovalent interactions between apple condensed tannins and cell walls on their transfer from fruit to juice: studies in model suspensions and application. AB - The adsorption of procyanidins (condensed tannins) on cell-wall material was quantified by bringing into contact solutions of procyanidins and suspensions of cell-wall material. A model was developed on the basis of the Langmuir isotherm formulation and a factorial experimental design. The parameters that influenced the adsorption were the concentration and molecular weight of the procyanidins, the ionic strength of the solution, the temperature, and the apple cell-wall concentration. The model was applied to partitioning of procyanidins from apple between juice and mash. The parameters to be taken into account are the composition of the apples and, specifically, (i) the concentration and molecular weight of the procyanidins, (ii) their acidity and pH as a determinant of the ionic strength, and (iii) their cell-wall content and the temperature at pressing. To estimate the ability of the model to relate procyanidin concentrations in the juice to their concentration in the apple, apples of three varieties of widely different procyanidin compositions were pressed in conditions that prevent oxidation. In these conditions, yields in the juice were >80% for phenolic acids or catechin monomers but <50% for procyanidins, with the lowest rates obtained for the higher polymers in accordance with the model. PMID- 17725316 TI - Inhibition of gastric H(+),K(+)-ATPase and Helicobacter pylori growth by phenolic antioxidants of Curcuma amada. AB - Gastric ulcer is the most prevalent gastrointestinal disorder, resulting from oxidative stress, Helicobacter pylori infection, up-regulation of proton potassium ATPase (PPA) activity, down-regulation of gastric mucosal defense, etc. In this paper it is reported that phenolic fractions of Curcuma amada, commonly known as mango ginger, acted as potent inhibitors of PPA and H. pylori growth. Mango ginger free phenolics (MGFP) and mango ginger bound phenolics (MGBP) inhibited PPA at IC50 values of 2.2 +/- 0.21 and 0.7 +/- 0.08 microg/mL, respectively, exhibiting 9-27-fold better potency over lansoprazole (IC(50) of 19.3 +/- 2.2 microg/mL). MGFP is constituted by caffeic (26%), gentisic (24%), ferulic (20%), gallic (10%), cinnamic (7%), and protocatechuic acids (7%) and MGBP by ferulic (47%), cinnamic (29%), p-coumaric acid (11%), and syringic (5%) acids as major phenolic acids. MGFP and MGBP further exhibited free radical scavenging (IC(50) of 2.2 +/- 0.17 and 4.2 +/- 0.36 microg/mL), reducing power abilities (193-104 units/g), inhibition of lipid peroxidation (IC(50) of 10.3 +/- 0.91 and 15.6 +/- 1.6 microg/mL), and DNA protection (80% at 4 microg), indicating strong antioxidative properties. MGFP and MGBP thus may be potential and inexpensive multistep blockers against ulcers. PMID- 17725317 TI - Detection of ruminant meat and bone meals in animal feed by real-time polymerase chain reaction: result of an interlaboratory study. AB - The commercialization of animal feeds infected by prions proved to be the main cause of transmission of bovine spongiform encephalopathy (BSE). Therefore, feed bans were enforced, initially for ruminant feeds, and later for all feeds for farmed animals. The development and validation of analytical methods for the species-specific detection of animal proteins in animal feed has been indicated in the TSE (Transmissible Spongiform Encephalopathies) Roadmap (European Commission. The TSE (Transmissible Spongiform Encephalopathy) roadmap. URL: http://europa.eu.int/comm/food/food/biosafety/bse/roadmap_en.pdf, 2005) as the main condition for lifting the extended feed ban. Methods based on polymerase chain reaction (PCR) seem to be a promising solution for this aim. The main objective of this study was to determine the applicability of four different real time PCR methods, developed by three National expert laboratories from the European Union (EU), for the detection and identification of cattle or ruminant species in typical compound feeds, fortified with meat and bone meals (MBM) from different animal species at different concentration levels. The MBM samples utilized in this study have been treated using the sterilization condition mandatory within the European Union (steam pressure sterilization at 133 degrees C, 3 bar, and 20 min), which is an additional challenge to the PCR methods evaluated in this study. The results indicate that the three labs applying their PCR methods were able to detect 0.1% of cattle MBM, either alone or in mixtures with different materials such as fishmeal, which demonstrates the improvement made by this technique, especially when compared with results from former interlaboratory studies. PMID- 17725318 TI - Influence of growth temperature on the amounts of tocopherols, tocotrienols, and gamma-oryzanol in brown rice. AB - Brown rice is a valuable source of lipid-soluble antioxidants including ferulated phytosterols (i.e., gamma-oryzanol), tocopherols, and tocotrienols. To evaluate the impact of temperature on the accumulation of these compounds, seeds from six different rice lines grown to maturity in replicate greenhouses in Gainesville, FL, were analyzed. The lines represented Oryza sativa indica, O. sativa japonica, and Oryza glaberrima of different origins. Temperatures were maintained near ambient at one end of each greenhouse and at approximately 4.5 degrees C above ambient at the other end. gamma-Oryzanols, tocopherols, and tocotrienols were extracted from whole seed (i.e., brown rice) and analyzed by HPLC. Tocotrienols and tocopherols varied widely between lines but changed only slightly with respect to temperature. In general, the proportions of alpha-tocotrienol and/or alpha-tocopherol increased at elevated temperature, whereas gamma-tocopherol and gamma-tocotrienol decreased. Six gamma-oryzanol peaks, identified on the basis of absorbance maxima at 330 nm and HPLC-mass spectrometry, were quantified. The most abundant component was 24-methylenecycloartanyl ferulate, present at 40-62% of total. Its levels increased 35-57% at elevated temperature in five of six lines, accounting for most of the change in total gamma-oryzanol. The results suggest that the physiological action of individual ferulated phytosterols should be investigated because their relative proportions in gamma-oryzanol can change. PMID- 17725322 TI - Square wave voltcoulometry: a tool for the study of strongly adsorbed redox molecules. AB - A new multipotential pulse technique called square wave voltcoulometry (SWVC), based on the analysis of the difference of converted charge signals obtained between two successive half-cycles when a square wave potential is applied, is developed to study charge-transfer processes taking place in electroactive monolayers. The use of SWVC presents the advantage of giving rise to a peak shaped response, which evolves to a charge plateau at high square wave pulse amplitudes, from which the total surface excess and the formal potential can be immediately measured for quasi-reversible and reversible processes. This characteristic represents its main advantage versus other multipotential step techniques, which lead to a negligible current under reversible conditions. The formal potential of the electroactive systems can be measured from the peak potential of the SWVC curves, even for quasi-reversible behavior. Moreover, the non-faradic effects on the response can be easily evaluated and avoided as is demonstrated in this paper. Experimental verification of the theoretical predictions is given for reversible and quasi-reversible systems. PMID- 17725319 TI - Synthesis and characterization of photocurable elastomers from poly(glycerol-co sebacate). AB - Elastomeric networks are increasingly being investigated for a variety of biomedical applications including drug delivery and tissue engineering. However, in some cases, their preparation requires the use of harsh processing conditions (e.g., high temperature), which limits their biomedical application. Herein, we demonstrate the ability to form elastomeric networks from poly(glycerol-co sebacate) acrylate (PGSA) under mild conditions while preserving a wide range of physical properties. These networks presented a Young's modulus between 0.05 and 1.38 MPa, an ultimate strength from 0.05 to 0.50 Mpa, and elongation at break between 42% and 189% strain, by varying the degree of acrylation (DA) of PGSA. The in vitro enzymatic and hydrolytic degradation of the polymer networks was dependent on the DA. The copolymerization of poly(ethylene glycol) diacrylate with PGSA allowed for an additional control of mechanical properties and swelling ratios in an aqueous environment, as well as enzymatic and hydrolytic degradation. Photocured PGSA networks demonstrated in vitro biocompatibility as judged by sufficient human primary cell adherence and subsequent proliferation into a confluent monolayer. These photocurable degradable elastomers could have potential application for the encapsulation of temperature-sensitive factors and cells for tissue engineering. PMID- 17725320 TI - Comment on "conformational changes and aggregation of alginic acid as determined by fluorescence correlation spectroscopy". PMID- 17725323 TI - Dissecting Tn5 transposition using HIV-1 integrase diketoacid inhibitors. AB - Diketoacid (DKA) compounds have been shown to inhibit HIV-1 integrase by a mechanism that involves sequestration of the active site metals. Because HIV-1 integrase and Tn5 transposase have similar active site architectures and catalytic mechanisms, we investigated whether DKA analogues would inhibit Tn5 transposase activity and provide a model system to explore the mechanisms of action of these inhibitors. A screen of several hundred DKA analogues identified several with activity against Tn5 Tnp. Six DKA inhibitors used in this study manifested a variety of effects on different transposition steps suggesting that different analogues may have different binding contacts with transposase. All DKA compounds inhibited paired end complex (PEC) formation in which the nucleoprotein complex required for catalysis is assembled. Dissociation of PECs by some DKA compounds indicates that these inhibitors can decrease PEC stability. Four DKA compounds inhibited the two cleavage steps releasing transposon DNA from flanking DNA, and one of these four compounds preferentially inhibited the second cleavage step. The differential effect of this inhibitor on the second cleavage event indicates that cleavage of the two transposon-donor DNA boundaries is a sequential process requiring a conformational change. The requirement for a conformational change between cleavage events was also demonstrated by the inability of transposase to perform second cleavage at 25 degrees C. Finally, all six compounds inhibit strand transfer, the final step of Tn5 transposition. Two of the compounds that inhibited strand transfer have no effect on DNA cleavage. The strand transfer inhibition properties of various DKA compounds was sensitive to the structure of the 5'-non-transferred strand, suggesting that these compounds bind in or near the transposase active site. Other results that probe compound binding sites include the effects of active site mutations and donor DNA on DKA compound inhibition activities. Thus, DKA inhibitors will provide an important set of tools to investigate the mechanism of action of transposases and integrases. PMID- 17725324 TI - Conformational changes during normal and error-prone incorporation of nucleotides by a Y-family DNA polymerase detected by 2-aminopurine fluorescence. AB - Y-family polymerases are specialized to carry out DNA synthesis past sites of DNA damage. Their active sites make fewer contacts to their substrates, consistent with the remarkably low fidelity of these DNA polymerases when copying undamaged DNA. We have used DNA containing the fluorescent reporter 2-aminopurine (2-AP) to study the reaction pathway of the Y-family polymerase Dbh. We detected 3 rapid noncovalent steps between binding of a correctly paired dNTP and the rate limiting step for dNTP incorporation. These early steps resemble those seen with high-fidelity DNA polymerases, such as Klenow fragment, and include a step that may be related to the unstacking of the 5' neighbor of the templating base that is seen in polymerase ternary complex crystal structures. A significant difference between Dbh and high-fidelity polymerases is that Dbh generates no fluorescence changes subsequent to dNTP binding if the primer lacks a 3'OH, suggesting that the looser active site of Y-family polymerases may enforce reliance on the correct substrate structure in order to assemble the catalytic center. Dbh, like other bypass polymerases of the DinB subgroup, generates single base deletion errors at an extremely high frequency by skipping over a template base that is part of a repetitive sequence. Using 2-AP as a reporter to study the base-skipping process, we determined that Dbh uses a mechanism in which the templating base slips back to pair with the primer terminus while the base that was originally paired with the primer terminus becomes unpaired. PMID- 17725325 TI - Interaction of syntaxin 1A with the N-terminus of Kv4.2 modulates channel surface expression and gating. AB - Kv4.2 channels are responsible in the heart for the Ca2+-independent transient outward currents and are important in regulating myocardial excitability and Ca2+ homeostasis. We have identified previously the expression of syntaxin 1A (STX1A) on the cardiac ventricular myocyte plasma membranes, and its modulation of cardiac ATP-sensitive K+ channels. We speculated that STX1A interacts with other cardiac ion channels, thus we examined the interaction of STX1A with Kv4.2 channels. Co-immunoprecipitation and GST pulldown assays demonstrated a direct interaction of STX1A with the Kv4.2 N-terminus. We next investigated the functional alterations of Kv4.2 gating by STX1A in Xenopus oocytes. Coexpression of Kv4.2 with STX1A (1) resulted in a reduction of Kv4.2 current amplitude; (2) caused a depolarizing shift of the steady-state inactivation curve; (3) enhanced the rate of current decay; and (4) accelerated the rate of recovery from inactivation. Additional coexpression of botulinum neurotoxin C, which cleaves STX1A, reversed the effects of STX1A on Kv4.2. STX1A inhibited partially the gating changes by KChIP2, suggesting a competitive interaction of these proteins for an overlapping binding region on the N-terminus of Kv4.2. Indeed, the N terminal truncation mutants of Kv4.2 (Kv4.2Delta2-40 and Kv4.2Delta7-11), which form part of the KChIP2 binding site, displayed reduced sensitivity to STX1A modulation. Our study suggests that STX1A directly modulates Kv4.2 current amplitude and gating through its interaction with an overlapping region of the KChIP binding motif domain on the Kv4.2 N-terminus. PMID- 17725326 TI - Contributions of the protein environment to the midpoint potentials of the A1 phylloquinones and the Fx iron-sulfur cluster in photosystem I. AB - Electrostatic calculations have predicted that the partial negative charge associated with D575PsaB plays a significant role in modulating the midpoint potentials of the A1A and A1B phylloquinones in photosystem I. To test this prediction, the side chain of residue 575PsaB was changed from negatively charged (D) to neutral (A) and to positively charged (K). D566PsaB, which is located at a considerable distance from either A1A or A1B, and should affect primarily the midpoint potential of FX, was similarly changed. In the 575PsaB variants, the rate of electron transfer from A1A to FX is observed to decrease slightly according to the sequence D/A/K. In the 566PsaB variants, the opposite effect of a slight increase in the rate is observed according to the same sequence D/A/K. These results are consistent with the expectation that changing these residues will shift the midpoint potentials of nearby cofactors to more positive values and that the magnitude of this shift will depend on the distance between the cofactors and the residues being changed. Thus, the midpoint potentials of A1A and A1B should experience a larger shift than will FX in the 575PsaB variants, while FX should experience a larger shift than will either A1A or A1B in the 566PsaB variants. As a result, the driving energy for electron transfer from A1A and A1B to FX will be decreased in the former and increased in the latter. This rationalization of the changes in kinetics is compared with the results of electrostatic calculations. While the altered amino acids shift the midpoint potentials of A1A, A1B, and FX by different amounts, the difference in the shifts between A1A and FX or between A1B and FX is small so that the overall effect on the electron transfer rate between A1A and FX or between A1B and FX is predicted to be small. These conclusions are borne out by experiment. PMID- 17725327 TI - Theory of time-resolved sum-frequency generation and its applications to vibrational dynamics of water. AB - A molecular theory of time-resolved sum-frequency generation (SFG) has been developed. The theoretical framework is constructed using the coupled-oscillator model in the adiabatic approximation. This theory can treat not only the vibrational spectroscopy but also vibrational dynamics. An application of this theory is also provided for estimation of the time constants of the intermolecular vibrational energy transfer between water molecules. This approach can be used for molecular analysis of the experimental results of Shen at al. on the SFG studies of vibrational dynamics of water. PMID- 17725328 TI - What can C1s photoelectron spectroscopy tell about structure and bonding in clusters of methanol and methyl chloride? AB - Single-component clusters of methanol and methyl chloride have been produced by adiabatic expansion, and their carbon 1s photoelectron spectra were recorded using synchrotron radiation and a high-resolution electron analyzer. The experimental spectra are interpreted by means of theoretical models based on molecular dynamics simulations. The data are used to explore to what extent core level photoelectron spectra may provide information on the bonding mechanism and the geometric structure of clusters of polar molecules. The results indicate that the cluster-to-monomer shift in ionization energy and also the width of the cluster peak may be used to distinguish between hydrogen bonding and weaker electrostatic interactions. Moreover, the larger width of the cluster peak in methanol clusters as compared to methyl chloride clusters is partly due to the structured surface of methanol clusters. Theoretical modeling greatly facilitates the analysis of core-level photoelectron spectra of molecular clusters. PMID- 17725329 TI - A mechanistic investigation of ethylene oxide hydrolysis to ethanediol. AB - The B3LYP/6-311+G(d,p) description is employed to study the heterolytic ring opening mechanisms under microsolvation conditions for ethylene oxide in acidic, neutral, and alkaline environments. In acid and alkaline media, a concerted trans S(N)2 reaction is strongly favored as compared to the corresponding cis reaction. The importance of the nucleophile, water in acidic media and hydroxide ion in alkaline media, for lowering the activation enthalpy is emphasized and activation energies of approximately 80 and approximately 60 kJ mol(-1) are obtained under acid and alkaline conditions, respectively. Under neutral conditions, the trans S(N)2 mechanism becomes inaccessible because it invokes the formation of a transient H+ and OH- pair across the 1,2-ethanediol molecule. Rather, epoxide ring opening is achieved by hydrolysis of a single water molecule. The latter mechanism displays significantly greater activation enthalpy (205 kJ mol(-1)) than those in acid and alkaline environments. This is in agreement with experiment. Product distributions of simple olefins in neutral aqueous media, as well as the detrimental impact of acid/base conditions for the selectivity of epoxidation catalysts in aqueous media, are discussed. PMID- 17725330 TI - Transient structures and kinetics of the ferrioxalate redox reaction studied by time-resolved EXAFS, optical spectroscopy, and DFT. AB - The photoredox reaction transients of ferrioxalate in water have been studied by means of time-resolved EXAFS and ultrafast optical transient spectroscopy. The transient spectra and kinetics have been measured from the femtosecond to millisecond range, and the Fe-O bond lengths of the ferrioxalate redox reaction transients have been determined with 2 ps time resolution and 0.04 A accuracy. These data in conjunction with quantum-chemistry DFT and UHF calculations were used to formulate a mechanism for the Fe(III) to Fe(II) redox reaction where dissociation precedes electron transfer. In addition, radical scavenging experiments support the mechanism proposed. PMID- 17725331 TI - Competition between energy transfer and interligand electron transfer in porphyrin-osmium(II) bis(2,2':6',2' '-terpyridine) dyads. AB - Rapid intramolecular energy transfer occurs from a free-base porphyrin to an attached osmium(II) bis(2,2':6',2' '-terpyridine) complex, most likely by way of the Forster dipole-dipole mechanism. The initially formed metal-to-ligand, charge transfer (MLCT) excited-singlet state localized on the metal complex undergoes very fast intersystem crossing to form the corresponding triplet excited state ((3)MLCT). This latter species transfers excitation energy to the (3)pi,pi* triplet state associated with the porphyrin moiety, such that the overall effect is to catalyze intersystem crossing for the porphyrin. Interligand electron transfer (ILET) to the distal terpyridine ligand, for which there is no driving force, competes poorly with triplet energy transfer from the proximal (3)MLCT to the porphyrin. Equipping the distal ligand with an ethynylene residue provides the necessary driving force for ILET and this process now competes effectively with triplet energy transfer to the porphyrin. The rate constants for all the relevant processes have been derived from laser flash photolysis studies. PMID- 17725332 TI - Topological characteristics of electron density distribution in SSXY --> XSSY (X or Y = F, Cl, Br, I) isomerization reactions. AB - The reactions of SSXY to XSSY (X or Y = F, Cl, Br, I) have been studied at B3LYP/6-311++G(2df) and MP2/6-311++G(2df) levels based on B3LYP/6-311++G(2df) optimized geometries. There are two pathways (X or Y atom transferring) for each reaction of SSXY to XSSY(X or Y = F, Cl, Br, I). The "Atoms in Molecules" theory has been applied to analyze the topological characteristics of electron density distribution along the reaction path. (a) The S-S-X or S-S-Y ring structure transition region (STR) is contributed to S(1)-X or S(1)-Y bond formation and S(2)-X or S(2)-Y bond annihilation. The STR and structure transition state (STS) are defined. (b) Comparing the two pathways of each SSXY --> XSSY (X, Y = F, Cl, Br, I) reaction, X or Y atom transferring, the broader the STR is, the later the STS appears, and the pathway is easier. (c) When X linked to the same S site of a three-member ring (S-S-F, S-S-Cl, S-S-Br, or S-S-I), the ring STR becomes broader and the STS appears later according to the sequence of X = F, Cl, Br, and I. And in these cases, for exothermic reactions, the higher the DeltaE(P-->TS1) is, the broader the STR is and the later the STS appears. (d) When the same Y atom linked to different three-member-ring S-S-X, the STR becomes broader and the STS appears later according to the sequence of X = F, Cl, Br, and I in the ring. And in these cases, for exothermic reactions, the lower the DeltaE(P-->TS2) is, the broader the STR is and the later the STS appears. PMID- 17725333 TI - Electronic to vibrational energy transfer assisted by interacting transition dipole moments: a quantum model for the nonadiabatic I2(E) + CF4 collisions. AB - We report a theoretical study of nonadiabatic transitions within the first-tier ion-pair states of molecular iodine induced by collisions with CF(4). We propose a model that treats the partner as a spherical particle with internal vibrational structure. Potential energy surfaces and nonadiabatic matrix elements for the I(2)-CF(4) system are evaluated using the diatomics-in-molecule perturbation theory. A special form of the intermolecular perturbation theory for quasi degenerate electronic states is implemented to evaluate the corrections to the long-range interaction of transition dipole moments of colliding molecules. The collision dynamics is studied by using an approximate quantum scattering approach that takes into account the coupling of electronic and vibrational degrees of freedom. Comparison with available experimental data on the rate constants and product state distributions demonstrates a good performance of the model. The interaction of the transition dipole moments is shown to induce very efficient excitation of the dipole-allowed upsilon(3) and upsilon(4) modes of the CF(4) partner. These transitions proceed predominantly through the near-resonant E-V energy transfer. The resonant character of the partner's excitation and the large mismatch in vibrational frequencies allow one to deduce the partner's vibrational product state distributions from the distributions measured for the molecule. The perspectives of the proposed theoretical model for treating a broad range of molecular collisions involving the spherical top partners are discussed. PMID- 17725334 TI - Symmetric double-well potential model and its application to vibronic spectra: studies of inversion modes of ammonia and nitrogen-vacancy defect centers in diamond. AB - In this paper, we have studied the vibronic transitions between two symmetric double-well potentials by proposing a model Hamiltonian consisting of a harmonic oscillator and a parturition described by a Gaussian function that leads to a double minima potential with a barrier between the two energy minima. Making use of the contour integral form of Hermite polynomials, we present a new formula that can calculate Franck-Condon factors of the system rigorously. The simulated vibronic spectra of ammonia and the negatively charged nitrogen-vacancy center in diamond are presented as an application of the formula. PMID- 17725335 TI - Theoretical investigation of carrier envelope phase dependence of all-optical poling with the third- and higher-order nonlinear processes. AB - Dependence of efficiency in all-optical poling with nonlinear processes, up to eighth order, is considered. The explicit form of the nonlinear susceptibility that is responsible for the poling is derived, which shows both CEP and phase mismatch dependence. On the basis of an analysis of pulse propagation in a nonlinear material, it is shown that one can identify the order of nonlinearity that is relevant to the poling process, relying on current technology of CEP stabilization and thin-film growth. PMID- 17725336 TI - Investigation of the typical triangular structure B3 in boron chemistry: insight into bare all-boron clusters used as ligands or building blocks. AB - Even though boron clusters are quite significant, bare boron clusters as ligands in chemical compounds are still unknown. Triangular B(3) is a key constituent of all-boron clusters and widely applied in the boron compounds. As a basic step toward understanding the assembly and stabilization of bare all-boron clusters and the possibility of their fusion during the cluster-assembly process, we made the first attempt to assemble the smallest bare all-boron unit B(3)-. Both the "homo-decked sandwich" and "hetero-decked sandwich" schemes were applied to the assembly of B(3)- at the B3LYP/6-311++G(d, p) level. For all the considered alkali- and alkaline earth metals, B(3)- can only be assembled in "hetero-decked sandwich" scheme (e.g., CpMB(3)(q-)) so as to avoid cluster fusion, whereas it cannot be assembled in the traditional "homo-decked sandwich" scheme (B(3)MB(3)(q )) because of thermodynamic and kinetic instability. Various assembled species in extended frameworks are designed. In particular, the dimerization of the hetero decked sandwich-like CpMB(3)(q-) could lead to a new type of antiaromatic triple decker sandwich-like complexes CpMB(6)Cp(2q-) that contain the all-boron antiaromatic unit B(6)(2-). Our work supports the experimental identification of the B(6)(2-) anion (with M+ counterions) in a photoelectron spectroscopy study. Additionally, the electronic and structural properties of B(3)- are well conserved during cluster-assembly, characteristic of a "superatom" feature. Our results are expected to be helpful for understanding the assembly and stabilization of bare all-boron cluster chemistry. Also, our work should give insight toward designing and understanding bare boron clusters as potential new ligands for coordination chemistry and as new building blocks for materials science. Interestingly, our results should provide hints to embellish, functionalize, isolate, and protect bare all-boron clusters. PMID- 17725337 TI - Synthesis, molecular modeling studies, and preliminary pharmacological characterization of all possible 2-(2'-sulfonocyclopropyl)glycine stereoisomers as conformationally constrained L-homocysteic acid analogs. AB - Bioisosteric replacements of the distal acidic group of L-glutamic acid (L-Glu, 1) and conformational constraining of its carbon skeleton, have been widely exploited to discover competitive modulators of glutamate receptors. Noteworthy, L-homocysteic acid (L-HCA, 18), a neurotransmitter belonging to the class of excitatory sulfur-containing amino acids, may be considered an endogenous occurring bioisoster of L-Glu (1). L-HCA (18) has been reported to mediate signaling between glial cells and postsynaptic neurons through the activation of glutamate receptors and others hitherto not well-characterized receptors. As a continuation of our work in the preparation of conformationally constrained glutamate analogs, we report the synthesis and the preliminary pharmacological characterization at iGluRs and mGluRs of all eight stereoisomers of 2-(2' sulfonocyclopropyl)glycine (SCGs, 8-15). Among the reported compounds, S-SCG-4 (15) showed to be a potent and relatively selective AMPA ligand. Docking experiments coupled to molecular electrostatic potential calculations allowed insight into the molecular basis of the activity of this compound to be gained. The library of SCGs (8-15), while providing a novel source of modulators of the glutamate receptors, represents a valuable chemical tool to better characterize L HCA pathways in the CNS. PMID- 17725338 TI - High-throughput screening of drug-brain tissue binding and in silico prediction for assessment of central nervous system drug delivery. AB - A high-throughput method for rapid screening of in vitro drug-brain homogenate binding is presented. The method is based on a straightforward sample pooling approach combining equilibrium dialysis with liquid chromatography mass spectrometry (LCMS). A strong correlation of fraction unbound in brain (fu) between single compound measurements and 25-pooled compounds (R2 = 0.906) was obtained for a selection of structurally diverse CNS compounds with a wide range of fractions unbound. Effects of brain homogenate dilution and dialysis time were investigated. To the best of our knowledge, it was the first time that we have demonstrated consistent fraction unbound in mouse and rat brain homogenate, revealing the drug-tissue partitioning mechanism predominated by hydrophobic interaction. On the basis of this finding, a generic approach to estimate drug binding to various tissues is proposed. A robust and interpretable QSAR for fu prediction is also presented by statistical modeling. PMID- 17725339 TI - Novel ATP-competitive kinesin spindle protein inhibitors. AB - Kinesin spindle protein (KSP), an ATPase responsible for spindle pole separation during mitosis that is present only in proliferating cells, has become a novel and attractive anticancer target with potential for reduced side effects compared to currently available therapies. We report herein the discovery of the first known ATP-competitive inhibitors of KSP, which display a unique activity profile as compared to the known loop 5 (L5) allosteric KSP inhibitors that are currently under clinical evaluation. Optimization of this series led to the identification of biphenyl sulfamide 20, a potent KSP inhibitor with in vitro antiproliferative activity against human cells with either wild-type KSP (HCT116) or mutant KSP (HCT116 D130V). In a murine xenograft model with HCT116 D130V tumors, 20 showed significant antitumor activity following intraperitoneal dosing, providing in vivo proof-of-principle of the efficacy of an ATP-competitive KSP inhibitor versus tumors that are resistant to the other known KSP inhibitors. PMID- 17725342 TI - Diffusion-limited unbinding of small peptides from PDZ domains. AB - PDZ domains are typical examples of binding motifs mediating the formation of protein-protein assemblies in many different cells. A quantitative characterization of the mechanisms intertwining structure, chemistry, and dynamics with the PDZ function represent a challenge in molecular biology. Here, we investigated the influence of native state topology on the thermodynamics and dissociation kinetics for a PDZ/peptide complex via molecular dynamics simulations based on a coarse-grained description of PDZ domains. Our native centric approach neglects chemical details but incorporates the basic structural information to reproduce the protein functional dynamics as it couples to binding. We found that at physiological temperatures the unbinding of a peptide from the PDZ domain becomes increasingly diffusive rather than thermally activated, as a consequence of the significant reduction of the free energy barrier with temperature. In turn, this results in a significant slowing down of the process of 2 orders of magnitude with respect to the conventional Arrhenius extrapolation from low-temperature calculations. Finally, a detailed analysis of a typical unbinding event based on the rupture times of single peptide-PDZ contacts allows us to shed further light on the dissociation mechanism and to elaborate a coherent picture of the relation between function and dynamics in PDZ domains. PMID- 17725341 TI - Vibrational-exciton couplings for the amide I, II, III, and A modes of peptides. AB - The couplings between all amide fundamentals and their overtones and combination vibrational states are calculated. Combined with the level energies reported previously (Hayashi, T.; Zhuang, W.; Mukamel, S. J. Phys. Chem. A 2005, 109, 9747), we obtain a complete effective vibrational Hamiltonian for the entire amide system. Couplings between neighboring peptide units are obtained using the anharmonic vibrational Hamiltonian of glycine dipeptide (GLDP) at the BPW91/6 31G(d,p) level. Electrostatic couplings between non-neighboring units are calculated by the fourth rank transition multipole coupling (TMC) expansion, including 1/R3 (dipole-dipole), 1/R4 (quadrupole-dipole), and 1/R5 (quadrupole quadrupole and octapole-dipole) interactions. Exciton delocalization length and its variation with frequency in the various amide bands are calculated. The simulated infrared amide I and II absorptions and CD spectra of 24 residue alpha helical motifs (SPE3) are in good agreement with experiment. PMID- 17725343 TI - Temperature-dependent magnetic field effect study on exciplex luminescence: probing the triton X-100 reverse micelle in cyclohexane. AB - The microenvironment within the reverse micelle of the nonionic surfactant Triton X-100 (TX-100) in cyclohexane has been investigated by studying the magnetic field effect (MFE) on pyrene-dimethylaniline exciplex luminescence. The nature of exciplex fluorescence and its behavior in the presence of a magnetic field have been found to vary significantly with the water content of the medium. Results are discussed in light of multiple exciplex formation within the micelle which is further supported by the fluorescence lifetime measurements. Those exciplexes emitting at longer wavelength are found to be magnetic field sensitive while those emitting toward the blue region of the spectrum are insensitive toward magnetic field. Since the exciplex's emission characteristics and magnetic field sensitivity depend on its immediate surrounding, it has been concluded that the environment within the micelle is nonuniform. With an increase in hydration level, different zones of varying polarity are created within the reverse micelle. It has been pointed out that the magnetic field sensitive components reside inside the polar core of the micelle while those located near the hydrocarbon tail are field insensitive. However it has been presumed that an interconversion between the different types of exciplexes is possible. The environment within the reverse micelle is found to be largely affected by the change in temperature, and this is reflected in the exciplex emission property and the extent of magnetic field effect. Interestingly, the variation of MFE with temperature follows different trends in the dry and the wet reverse micelle. A comparison has been drawn with the reverse micelle of the ionic surfactant to get an insight into the difference between the various types of micellar environment. PMID- 17725340 TI - Design, synthesis, and characterization of a dual modality positron emission tomography and fluorescence imaging agent for monoclonal antibody tumor-targeted imaging. AB - A novel lysine-based trifunctional chelate 3 was designed, synthesized, and characterized and bears both a chelating moiety (CHX-A' ') for sequestering radiometals (86Y or 111In) and the near-infrared dye Cy5.5 for dual modality PET (or SPECT) and fluorescence imaging, respectively. Successful conjugation of 3 to the monoclonal antibody trastuzumab (Herceptin) was achieved by efficient thiol maleimide chemistry, thereby yielding immunoconjugate 2. Analysis of 2 by flow cytometry and competitive binding assay demonstrates that immunoconjugate 2 binds to SKOV3 tumor cells comparably to native trastuzumab and, thus, may be used as a tumor-targeted monoclonal antibody probe for multimodality imaging. PMID- 17725344 TI - Terbium luminescence sensitized through three-photon excitation in a self assembled unlinked antenna. AB - The organic-terbium hybrid compound designed with the azido molecule L, 2-methoxy benzoic acid tris-(2-methoxybenzoyl)hydrazide, exhibits three-photon-excited green emission as well as second-harmonic generation even though the antenna is unlinked from the metal center. PMID- 17725346 TI - New series of indium formates: hydrothermal synthesis, structure and coordination modes. AB - Three new indium(III) compounds, In(HCOO)3 (1), In2(HCOO)5(OH) (2), and In(HCOO)2(OH) (3), were synthesized under hydrothermal conditions and characterized by single crystal and powder X-ray diffraction experiments, as well as by IR spectroscopy, elemental analysis, and coupled TG-DSC-MS measurement. All of these compounds adopt 3D framework structures consisting of InO6 octahedra and the 2.11 binding modes of formate with the (syn, syn-; syn, anti-; anti, anti-) configurations. The structural investigation of these indium formates reveals that the gradual introduction of the hydroxyl groups into the structures induces the polymerization of the InO6 octahedra, that is, InO6 is isolated in 1, becomes dimeric in 2, and finally forms 1D chains in 3. In addition, a simple formula that may be used for estimating the overall coordination number of the formate in Ma(HCOO)bLc is proposed. PMID- 17725345 TI - Computational studies of EPR parameters for paramagnetic molybdenum complexes. II. Larger MoV systems relevant to molybdenum enzymes. AB - The careful validation of modern density functional methods for the computation of electron paramagnetic resonance (EPR) parameters in molybdenum complexes has been extended to a number of low-symmetry MoV systems that model molybdoenzyme active sites. Both g and hyperfine tensors tend to be reproduced best by hybrid density functionals with about 30-40% exact-exchange admixture, with no particular spin contamination problems encountered. Spin-orbit corrections to hyperfine tensors are mandatory for quantitative and, in some cases, even for qualitative agreement. The g11 (g||) component of the g tensor tends to come out too positive when spin-orbit coupling is included only to leading order in perturbation theory. Compared to single-crystal experiments, the calculations reproduce both g- and hyperfine-tensor orientations well, both relative to each other and to the molecular framework. This is significant, as simulations of the EPR spectra of natural-abundance frozen-solution samples frequently do not allow a reliable determination of the hyperfine tensors. These may now be extracted based on the quantum-chemically calculated parameters. In a number of cases, revised simulations of the experimental spectra have brought theory and experiment into substantially improved agreement. Systems with two terminal oxo ligands, and to some extent with an oxo and a sulfido ligand, have been confirmed to exhibit particularly large negative Deltag33 shifts and thus large g anisotropies. This is discussed in the context of the experimental data for xanthine oxidase. PMID- 17725347 TI - Metal-porphyrin orbital interactions in highly saddled low-spin iron(III) porphyrin complexes. AB - Substituent effects of the meso-aryl (Ar) groups on the 1H and 13C NMR chemical shifts in a series of low-spin highly saddled iron(III) octaethyltetraarylporphyrinates, [Fe(OETArP)L2]+, where axial ligands (L) are imidazole (HIm) and tert-butylisocyanide ((t)BuNC), have been examined to reveal the nature of the interactions between metal and porphyrin orbitals. As for the bis(HIm) complexes, the crystal and molecular structures have been determined by X-ray crystallography. These complexes have shown a nearly pure saddled structure in the crystal, which is further confirmed by the normal-coordinate structural decomposition method. The substituent effects on the CH2 proton as well as meso and CH2 carbon shifts are fairly small in the bis(HIm) complexes. Since these complexes adopt the (d(xy))2(d(xz), d(yz))3 ground state as revealed by the electron paramagnetic resonance (EPR) spectra, the unpaired electron in one of the metal dpi orbitals is delocalized to the porphyrin ring by the interactions with the porphyrin 3e(g)-like orbitals. A fairly small substituent effect is understandable because the 3e(g)-like orbitals have zero coefficients at the meso carbon atoms. In contrast, a sizable substituent effect is observed when the axial HIm is replaced by (t)BuNC. The Hammett plots exhibit a large negative slope, -220 ppm, for the meso-carbon signals as compared with the corresponding value, +5.4 ppm, in the bis(HIm) complexes. Since the bis((t)BuNC) complexes adopt the (d(xz), d(yz))4(d(xy))1 ground state as revealed by the EPR spectra, the result strongly indicates that the half-filled dxy orbital interacts with the specific porphyrin orbitals that have large coefficients on the meso-carbon atoms. Thus, we have concluded that the major metal-porphyrin orbital interaction in low-spin saddle-shaped complexes with the (d(xz), d(yz))4(d(xy))1 ground state should take place between the d(xy) and a(2u)-like orbital rather than between the dxy and a(1u)-like orbital, though the latter interaction is symmetry-allowed in saddled D(2d) complexes. Fairly weak spin delocalization to the meso-carbon atoms in the complexes with electron-withdrawing groups is then ascribed to the decrease in spin population in the d(xy) orbital due to a smaller energy gap between the d(xy) and dpi orbitals. In fact, the energy levels of the d(xy) and dpi orbitals are completely reversed in the complex carrying a strongly electron withdrawing substituent, the 3,5-bis(trifluoromethyl)phenyl group, which results in the formation of the low-spin complex with an unprecedented (d(xy))2(d(xz), d(yz))3 ground state despite the coordination of (t)BuNC. PMID- 17725348 TI - An unusual reaction: a GaCl3-assisted methyl/chlorine exchange in silylated hydrazinodichloroarsane. AB - N,N',N'-[Tris(trimethylsilyl)]hydrazino(dichloro)arsane, (Me3Si)2N-N(SiMe3)-AsCl2 (1), has been transformed into the corresponding N-trimethylsilyl-N',N'-bis (dimethylchlorosilyl)hydrazinodimethylarsane in a two-step synthesis: (i) Addition of GaCl3 to 1 results in the formation of the corresponding hydrazinodimethylarsane GaCl3 adduct (2). (ii) Reaction of 2 with 4 (dimethylamino)pyridine (DMAP) yielded the adduct-free hydrazinodimethylarsane (3). The intriguing methyl/chlorine exchange with GaCl3 as transfer/exchange reagent represents a new synthetic route to the hitherto unknown N-trimethylsilyl N',N'-bis-(dimethylchlorosilyl)hydrazinodimethylarsane in contrast to the same reaction of the phosphorus analogue that results in the formation of triazadiphospholes. The new exchange reaction was unambiguously proven by NMR and X-ray studies (1: monoclinic, P2(1)/c, a = 9.5002(19) A, b = 13.840(3) A, c = 17.226(5) A, beta = 120.12(2) degrees ; V = 1959.1(8) A3, Z = 4; 2: orthorhombic, Pbca; a = 11.7766(2) A, b = 13.9927(2) A, c = 28.3298(4) A; V = 4668.37(12) A3, Z = 4; 3: monoclinic, P2(1)/c, a = 12.015(2) A, b = 12.466(3) A, c = 13.031(3) A, beta = 98.20(3) degrees ; V = 1931.8(7) A3, Z = 4). Structural comparisons of the hydrazinoarsanes with their GaCl3 adducts provide interesting similarities and differences. Computations at the B3LYP level reveal that the exchange process is 34 kcal/mol exergonic. PMID- 17725349 TI - PtII-mediated 1,3-dipolar cycloaddition of oxazoline N-oxides to nitriles as a key step to dihydrooxazolo-1,2,4-oxadiazoles. AB - A novel type of heterocycle, viz., 2,3a-disubstituted 5,6-dihydro-3aH [1,3]oxazolo[3,2-b][1,2,4]oxadiazoles, was generated by an intermolecular PtII mediated 1,3-dipolar cycloaddition (1,3-DCA) between the oxazoline N-oxide C(Me)2CH2OC(R)=N+(O-) (R = Me, Et) and coordinated nitriles in the complexes trans/cis-[PtCl2(R'CN)2] [R' = Me, Et, CH2Ph, Ph, N(C5H10)]. The reaction is unknown for free RCN and oxazoline N-oxides, but under PtII-mediated conditions, it proceeds smoothly (CH2Cl2, 20-25 degrees C, 18-20 h) and gives pure complexes [PtCl2{N=C(R')ONC(R)OCH2CMe2}2] [R/R' = Me/Me, 1; Me/Et, 2; Me/CH2Ph, 3; Me/Ph, 4; Me/N(C5H10), 5; Et/Me, 6; Et/Et, 7; Et/CH2Ph, 8; Et/Ph, 9; Et/N(C5H10), 10] in 42-84% yields after column chromatography. Compounds 1-10 were characterized by elemental analyses (C, H, N), FAB+-MS, IR, and 1H and 13C{1H} NMR spectroscopies, and X-ray diffraction (for 1, 2, 5, and 9). With the exception of benzonitrile complexes, 1,3-DCA of oxazoline N-oxides to the PtII-ligated nitriles occurred diastereoselectively and afforded mixtures of enantiomers. Depending on the substituents on nitriles, asymmetric atoms in both of the formed heterocyclic ligands have the same (SS/RR) or different (SR/RS) configurations. The heterocyclic ligands were liberated from 1-4 and 6-9 by treatment with excess ethane-1,2-diamine (en) in CH2Cl2 for 1 day at 20-25 degrees C (for R' = Me, Et, CH2Ph) and at 50 degrees C (for R' = Ph) to achieve the free organic species and the well-known [Pt(en)2](Cl)2; the products were separated, and 2,3a disubstituted 5,6-dihydro-3aH-[1,3]oxazolo[3,2-b][1,2,4]oxadiazoles (11-18) were characterized by ESI+-MS and 1H and 13C{1H} NMR spectroscopies. PMID- 17725350 TI - Time-resolved studies of water dynamics and proton transfer at the alumina-air interface. AB - The present study aims to understand the dynamical properties of water and OH groups layered on an alumina surface mainly by means of femtosecond IR-pump IR probe transient absorption spectroscopy. The experimental results obtained demonstrate the existence of several kinds of O-H vibrators on the surface of alumina membranes, distinguishing them by their behavior on the femtosecond time scale and by the anisotropy of their spectral response. In the high-frequency region (>3400 cm-1), the absorption is due to well-packed aluminol groups and to physisorbed water patches on the surface. When pumping at 3200 cm-1, physisorbed water hydrogen-bonded to AlOH2+ groups is observed. The anisotropy measurements demonstrate the existence of an efficient energy-transfer mechanism among the water molecules characterized by a time constant of 400 +/- 100 fs. The persisting anisotropy at long times, especially in the case of AlOH groups and of the structured physisorbed water layer on top of them, proves the anisotropic structuring induced by the surface. The excitation at 3000 cm-1 enables the detection of a photon-induced proton-transfer reaction. The proton back-transfer reaction time constant is 350 +/- 50 fs. From anisotropy measurements, we estimate the proton hopping time to be 900 +/- 100 fs in a locally extended water network lying on the surface. PMID- 17725351 TI - Synthesis and glycosylation of a series of 6-mono-, di-, and trifluoro S-phenyl 2,3,4-tri-O-benzyl-thiorhamnopyranosides. Effect of the fluorine substituents on glycosylation stereoselectivity. AB - A series of 6-mono-, di-, and trifluoro analogs of S-phenyl 2,3,4-tri-O-benzyl-D- or L-thiorhamnopyranoside has been synthesized and used as donors in glycosylation reactions, with activation by the 1-benzenesulfinyl piperidine/triflic anhydride system. The stereochemical outcome of the glycosylation reactions was found to depend on the electron-withdrawing capability of the disarming substituent at the 6-position, i.e., on the number of fluorine atoms present. The results are explained with regard to the increased stability of the glycosyl triflates, shown to be intermediates in the reaction by low-temperature 1H NMR experiments, with increased fluorine content. PMID- 17725353 TI - Dendrimer-mediated transfer printing of DNA and RNA microarrays. AB - This paper describes a new method to replicate DNA and RNA microarrays. The technique, which facilitates positioning of DNA and RNA with submicron edge resolution by microcontact printing (muCP), is based on the modification of poly(dimethylsiloxane) (PDMS) stamps with dendrimers ("dendri-stamps"). The modification of PDMS stamps with generation 5 poly(propylene imine) dendrimers (G5-PPI) gives a high density of positive charge on the stamp surface that can attract negatively charged oligonucleotides in a "layer-by-layer" arrangement. DNA as well as RNA is transfer printed from the stamp to a target surface. Imine chemistry is applied to immobilize amino-modified DNA and RNA molecules to an aldehyde-terminated substrate. The labile imine bond is reduced to a stable secondary amine bond, forming a robust connection between the polynucleotide strand and the solid support. Microcontact printed oligonucleotides are distributed homogeneously within the patterned area and available for hybridization. By using a robotic spotting system, an array of hundreds of oligonucleotide spots is deposited on the surface of a flat, dendrimer-modified stamp that is subsequently used for repeated replication of the entire microarray by microcontact printing. The printed microarrays are characterized by homogeneous probe density and regular spot morphology. PMID- 17725354 TI - trans-RhCl(CO)(PPh3)2-catalyzed monomeric and dimeric cycloisomerization of propargylic 2,3-dienoates. Establishment of alpha,beta-unsaturated delta-lactone rings by cyclometallation. AB - Cyclometallation of two unsaturated carbon-carbon bonds usually requires the application of low-valent metal catalysts, which could cleave the propargylic ester linkage. Thus, it is desirable to identify a catalyst which could undergo cyclometallation without cleaving the propargylic ester linkage. In this paper, we used trans-RhCl(CO)(PPh(3))(2) to realize the cyclometallation of propargylic 2,3-dienoates. The substituents at the 4-position of allenoate moiety nicely control the reaction pathway: when the 4-position of propargylic 2,3-dienoate 1 was monosubstituted with an aryl group, the bicyclic intermediate 7 formed by the cyclometallation could highly selectively undergo carbometalation with the alkyne moiety in the second molecule of propargylic 2,3-dienoate 1 to afford metallabicyclic intermediates 8a or 8b. Subsequent reductive elimination would afford 9, which could undergo an intramolecular Diels-Alder reaction resulting in the formation of polycyclic bis(delta-lactone)-containing structures 2. The intermediate could be trapped by adding 3-methoxyprop-1-yne affording cyclization aromatization product 4p highly selectively. If the substituent at the 4-positon of the 2,3-allenoate moiety has a beta-H atom, sequential unimolecular cyclometallation/beta-H elimination/reductive elimination occurs to afford cross conjugated 5(Z)-alkylidene-4-alkenyl-5,6-dihydropyran-2-ones. The Z stereochemistry of the exo double bond was determined by the cyclometallation. Some of the alpha,beta-unsaturated delta-lactones could be easily converted to other synthetically useful compounds via reduction reaction, hydrogenation, and iodination/coupling protocol. PMID- 17725352 TI - Proton-detected solid-state NMR spectroscopy of fully protonated proteins at 40 kHz magic-angle spinning. AB - Remarkable progress in solid-state NMR has enabled complete structure determination of uniformly labeled proteins in the size range of 5-10 kDa. Expanding these applications to larger or mass-limited systems requires further improvements in spectral sensitivity, for which inverse detection of 13C and 15N signals with 1H is one promising approach. Proton detection has previously been demonstrated to offer sensitivity benefits in the limit of sparse protonation or with approximately 30 kHz magic-angle spinning (MAS). Here we focus on experimental schemes for proteins with approximately 100% protonation. Full protonation simplifies sample preparation and permits more complete chemical shift information to be obtained from a single sample. We demonstrate experimental schemes using the fully protonated, uniformly 13C,15N-labeled protein GB1 at 40 kHz MAS rate with 1.6-mm rotors. At 500 MHz proton frequency, 1 ppm proton line widths were observed (500 +/- 150 Hz), and the sensitivity was enhanced by 3 and 4 times, respectively, versus direct 13C and 15N detection. The enhanced sensitivity enabled a family of 3D experiments for spectral assignment to be performed in a time-efficient manner with less than a micromole of protein. CANH, CONH, and NCAH 3D spectra provided sufficient resolution and sensitivity to make full backbone and partial side-chain proton assignments. At 750 MHz proton frequency and 40 kHz MAS rate, proton line widths improve further in an absolute sense (360 +/- 115 Hz). Sensitivity and resolution increase in a better than linear manner with increasing magnetic field, resulting in 14 times greater sensitivity for 1H detection relative to that of 15N detection. PMID- 17725355 TI - A triphenylamine-containing donor-acceptor molecule for stable, reversible, ultrahigh density data storage. PMID- 17725356 TI - Resting state and kinetic studies on the asymmetric allylic substitutions catalyzed by iridium-phosphoramidite complexes. PMID- 17725357 TI - Programmed dynamic covalent assembly of unsymmetrical macrocycles. PMID- 17725358 TI - A silicon-based approach to oligoarenes by iterative cross-coupling reactions of halogenated organo[(2-hydroxymethyl)phenyl]dimethylsilanes. PMID- 17725360 TI - Synthesis and applications of novel bis(ammonium) chiral ionic liquids derived from isomannide. AB - Carbohydrate-based novel bis(ammonium) chiral ionic liquids have been synthesized by following a straightforward protocol using isomannide as the substrate. Their applications in chiral discrimination and optical resolution of racemates have been established. PMID- 17725361 TI - Enantioselective iridium-catalyzed allylic amination of ammonia and convenient ammonia surrogates. AB - Iridium-catalyzed, asymmetric allylation of ammonia as a nucleophile occurs with stereoselectivity to form a symmetric diallylamine, and related allylation of the inexpensive ammonia equivalent potassium trifluoroacetamide or the highly reactive ammonia equivalent lithium di-tert-butyliminodicarboxylate forms a range of conveniently protected, primary, alpha-branched allylic amines in high yields, high branched-to-linear regioselectivities, and high enantiomeric excess. The reactions of ammonia equivalents were conducted with a catalyst generated from a phosphoramidite containing a single stereochemical element. PMID- 17725362 TI - Efficient synthesis of maleimides and carbazoles via Zn(OTf)(2)-catalyzed tandem annulations of isonitriles and allenic esters. AB - Lewis acid Zn(OTf)(2)-catalyzed tandem annulations of isonitriles and allenic esters which lead to efficient and flexible syntheses of a range of biologically significant maleimides and carbazoles and related compounds are reported. A mechanistic rationale is proposed to account for the observed reactivity. PMID- 17725363 TI - Protein-resistant silicones: incorporation of poly(ethylene oxide) via siloxane tethers. AB - Silicones with enhanced protein resistance were prepared by introducing poly(ethylene oxide) (PEO) chains via siloxane tethers (a-c) of varying lengths. Three unique ambifunctional molecules (a-c) having the general formula alpha (EtO)3Si(CH2)2-oligodimethylsiloxanen-block-poly(ethylene oxide)8-OCH3 (n = 0 (a), 4, (b), and 13 (c)) were prepared via regioselective Rh-catalyzed hydrosilylation. Nine films were subsequently produced by the H3PO4-catalyzed sol gel cross-linking of a-c each with alpha,omega-bis(Si-OH)polydimethylsiloxane (P, Mn = 3000 g/mol) in varying ratios (1:1, 1:2, and 2:3 molar ratio a, b, or c to P). Films prepared with a 2:3 molar ratio (a-c to P) contained the least amount of un-cross-linked materials, which may migrate to the film surface. For this set of films, surface hydrophilicity and protein resistance increased with siloxane tether length (a-c). These results indicate that PEO was more effectively mobilized to the surface if incorporated into silicones via longer siloxane tethers. PMID- 17725364 TI - Development of a renal microchip for in vitro distal tubule models. AB - Current developments in tissue engineering and microtechnology fields have allowed the proposal of pertinent tools, microchips, to investigate in vitro toxicity. In the framework of the proposed REACH European directive and the 3R recommendations, the purpose of these microtools is to mimic organs in vitro to refine in vitro culture models and to ultimately reduce animal testing. The microchip consists of functional living cell microchambers interconnected by a microfluidic network that allows continuous cell feeding and waste removal controls by fluid microflow. To validate this approach, Madin Darby Canine Kidney (MDCK) cells were cultivated inside a polydimethylsiloxane microchip. To assess the cell proliferation and feeding, the number of inoculated cells varied from 5 to 10 x 10(5) cells/microchip (corresponding roughly to 2.5 to 5 x 10(5) cells/cm2) and from four flow rates 0, 10, 25, and 50 microL/min were tested. Morphological observations have shown successful cell attachment and proliferation inside the microchips. The best flow rate appears to be 10 microL/min with which the cell population was multiplied by about 2.2 +/- 0.1 after 4 days of culture, including 3 days of perfusion (in comparison to 1.7 +/- 0.2 at 25 microL/min). At 10 microL/min flow rate, maximal cell population reached about 2.1 +/- 0.2 x 10(6) (corresponding to 7 +/- 0.7 x 10(7) cells/cm(3)). The viability, assessed by trypan blue and lactate deshydrogenase measurements, was found to be above 90% in all experiments. At 10 microL/min, glucose monitoring indicated a cell consumption of 16 +/- 2 microg/h/10(6) cells, whereas the glutamine metabolism was demonstrated with the production of NH3 by the cells about 0.8 +/- 0.4 micromol/day/10(6) cells. Augmentation of the flow rate appeared to increase the glucose consumption and the NH3 production by about 1.5- to 2-fold, in agreement with the tendencies reported in the literature. As a basic chronic toxicity assessment in the microchips, 5 mM and 10 mM ammonium chloride loadings, supplemented in the culture media, at 0, 10, and 25 micaroL/min flow rates were performed. At 10 microL/min, a reduction of 35% of the growth ratio with 5 mM and of 50% at 10 mM was found, whereas at 25 microL/min, a reduction of 10% with 5 mM and of 30% at 10 mM was obtained. Ammonium chloride contributed to increase the glucose consumption and to reduce the NH3 production. The microchip advantages, high surface/volume ratio, and dynamic loadings, coupled with the concordance between the present and literature results dealing with ammonia/ammonium effects on MDCK illustrate the potential of our microchip for wider in vitro chronic toxicity investigations. PMID- 17725365 TI - Development of a particle bombardment-mediated transient transformation system for Taxus spp. cells in culture. AB - In developing and developed nations, plant cell culture systems are used to supply desirable compounds in lieu of chemical synthesis or natural extraction. When plant cell culture systems are unable to meet commercial demand, metabolic engineering offers a method to increase yields. However, to benefit from metabolic engineering approaches, effective transient transformation methods are required to rapidly identify and characterize key regulatory genes before intensive, time-consuming stable transformation efforts can proceed. This paper describes a particle bombardment-mediated transient transformation system for Taxus spp. in cell culture. Optimal parameters were established for the T. cuspidata cell line P991 and the T. canadensis cell line CO93D, resulting in reliable, efficient, transient expression of the firefly luciferase gene under control of the constitutive CaMV 35S promoter. Multiple bombardments and larger gold microcarriers (1.6 vs 1.0 microm in diameter) were particularly effective in increasing luciferase activity and in reducing variation among replicates. This particle bombardment-mediated transformation system was also shown to be capable of transiently expressing the DsRed and beta-glucuronidase reporter genes under the control of the maize ubiquitin and CaMV 35S promoters, respectively. With the ability to transiently transform Taxus spp. cell cultures using a variety of promoters and reporters, characterization of genes related to paclitaxel accumulation in culture can now proceed. PMID- 17725366 TI - Colorimetric recognition of anions using preorganized tetra-amidourea derived calix[4]arene sensors. AB - The synthesis and the spectroscopic studies of the amidourea based calix[4]arene sensors 1 and 2 are described. The 4-nitrophenyl based sensor 1 was synthesized in two steps from the corresponding calix [4]arene tetraethyl ester and shown to give rise to color changes in the UV-vis spectra in DMSO upon recognition of pyrophosphate and fluoride. Fitting the changes in the absorption spectra using nonlinear regression analysis indicated strong binding of several anions by 1 such as acetate and hydrogen phosphate in 1:1 (Host:Guest) stoichiometry, and at higher concentration in 1:2 stoichiometry. The preorganized calix-cavity was, however, not found to host chlorine while binding of bromide was determined. At high concentrations of these anions, significant colorimetric changes were also observed that were clearly visible to the naked eye for both pyrophosphate and fluoride. The phenyl analogue 2 was made to enable analysis of the anion recognition using 1H NMR titrations and showed that ions such as phosphate were bound in 1:1 stoichiometry, whereas the "urea" protons were shown to be significantly affected upon coordination to the anion. PMID- 17725367 TI - An acidity scale of 1,3-dialkylimidazolium salts in dimethyl sulfoxide solution. AB - Equilibrium acidities of 16 1,3-dialkylimidazolium-type ionic liquid (IL) molecules (1-16) were systematically measured by the overlapping indicator method at 25 degrees C in dimethyl sulfoxide (DMSO) solution. The pKa values were observed to range from 23.4 for IL 12 to 19.7 for IL 6 (Tables 1 and 2), responding mainly to structural variations on the cation moiety. Excellent agreement between the spectrophotometrically determined pKa and that derived from NMR titration for 1,3,4,5-tetramethylimidazolium bis(trifluoromethanesulfonyl)imide (12) and the close match of the obtained pK values with the reported data in literature provide credence to the acidity measurements of the present work. The substituent effects at the imidazolium ring and the effects of counterions on the acidities of ionic liquids are discussed. PMID- 17725368 TI - Equilibrium surface adsorption behavior in complex anionic/nonionic surfactant mixtures. AB - Neutron reflectivity (NR) and small angle neutron scattering (SANS) have been used to investigate the equilibrium surface adsorption behavior and the solution microstructure of mixtures of the anionic surfactant sodium 6-dodecyl benzene-4 sulfonate (SDBS) with the nonionic surfactants monododecyl octaethylene glycol (C12EO8) and monododecyl triiscosaethylene glycol (C12EO23). In the SDBS/C12EO8 and SDBS/C12EO23 solutions, small globular mixed micelles are formed. However, the addition of Ca2+ ions to SDBS/C12EO8 results in a transition to a vesicle phase or a mixed vesicle/micellar phase for SDBS rich compositions. In contrast, this transition hardly exists for the SDBS/C12EO23 mixture, and occurs only in a narrow composition region which is rich in SDBS. The adsorption of the SDBS/C12EO8 mixture at the air-solution interface is in the form of a mixed monolayer, with a composition variation that is not consistent with ideal mixing. In water and in the presence of NaCl, the nonideality can be broadly accounted for by regular solution theory (RST). At solution compositions rich in SDBS, the addition of Ca2+ ions results in the formation of multilayer structures at the interface. The composition range over which multilayer formation exists depends upon the Ca2+ concentration added. In comparison, the addition of a simple monovalent electrolyte, NaCl, at the same ionic strength does not have the same impact upon the adsorption, and the surface structure remains as a monolayer. Correspondingly, in solution, the mixed surfactant aggregates remain as relatively small globular micelles. In the presence of Ca2+ counterions, the variation in surface composition with solution composition is not well described by RST over the entire composition range. Furthermore, the mixing behavior is not strongly correlated with variations in the solution microstructure, as observed in other related systems. PMID- 17725370 TI - Simulations of cyclic voltammetric and chronoamperometric electrode responses at a disk electrode using combinations of spherical and cylindrical electrode geometries. AB - Using geometric models based on one-dimensional transport at spheres and cylinders, three methods for improving the simulation of voltammetric behavior of a disk electrode have been explored. One method is based on the common assumption of equivalency between the limiting currents for a disk and a hemisphere under steady-state diffusion conditions. The second method involves the use of a partial-sphere geometry which is a better approximation that is suitable at the extreme diffusional limits achievable at a disk electrode of fully planar and steady-state transport. The third method, which is generally applicable, is a further refinement that uses a combination of appropriate one-dimensional spherical and cylindrical geometries. The results demonstrate that reasonably accurate approximations of disk behavior for several reaction mechanisms can be achieved in a fraction of the time required to compute the more rigorous two dimensional model. We propose that the approximation serve primarily as a fast way to explore system behavior and establish approximate values of the relevant parameters. More accurate computations can then be performed using the two dimensional model. PMID- 17725371 TI - Photoluminescence of a freely suspended monolayer of quantum dots encapsulated into layer-by-layer films. AB - A single monolayer of CdSe/ZnS quantum dots (QDs) has been encapsulated into a 60 nm free-suspended layer-by-layer (LbL) film. The QD monolayer showed a low light emission within this film in contact with supporting solid substrates, but the manifold increase of photoluminescencence intensity was observed when the film was lifted and freely suspended over the microfabricated cylindrical cavities. This phenomenon was discussed in relationship with the effect of the elimination of the surface quenching enhanced by optical reflection from highly reflective silicon cavities. We suggest that a significant increase of the photoluminescence intensity of QD monolayers suspended over the microfabricated array can be interesting for future diagnostic and sensing applications. PMID- 17725369 TI - Study of the formation of self-assembled monolayers on nitinol. AB - Shape memory alloys such as nitinol (NiTi) have gained interest due to their unique and unusual properties of thermal shape memory, superelasticity, and good damping properties. Nitinol is mainly used for medical purposes. In order to control the surface properties of this alloy, self-assembled monolayers (SAMs) were formed and characterized on the native oxide surface of nitinol for the first time. Factors which affect the formation of SAMs, such as head group functionality, chain length, and tail group functionality, were varied and analyzed. Functionalized alkyl phosphonic acid molecules (OH, COOH, and CH3) formed monolayers on the nitinol surface using a simple deposition method resulting in the molecules being ordered and strongly bound to the surface. Diffuse reflectance infrared spectroscopy (DRIFT), contact angle goniometry, atomic force microscopy (AFM), and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used to characterize the surfaces before and after organic modification. PMID- 17725372 TI - Polymeric optical microscreen for high-resolution surface plasmon resonance microarray imaging. AB - In this study, we demonstrate a simple method to fabricate surface plasmon resonance (SPR) imaging microarrays using polymer micropatterns. The use of a micrometer-scale polymeric optical screen (microPOS) passivates the region deposited with polymer by completely removing SPR signals or by saturating the SPR signal far beyond the detection range of SPR imaging. Two schemes were suggested to create a surface microPOS by either micropatterning a thick insulating layer before deposition of a metal layer (complete removal of SPR) or after deposition of a metal layer (saturation of SPR signal). The two schemes were successfully applied for the imaging of biological adsorption with a high imaging resolution of approximately 100 microm/pattern and 10 microm separation. The validity of the system was verified with a biotin-streptavidin system as a model for the systematic binding of biomolecules. Further, binding of prostate specific antigen (PSA) onto the anti-PSA SPR microarray was demonstrated as a useful method for detecting a cancer marker. PMID- 17725373 TI - Interaction between dendrons directly studied by single-molecule force spectroscopy. AB - In this article, we have investigated the interaction between two poly(benzyl ether) dendrons directly by single-molecule force spectroscopy. For this purpose, one dendron was immobilized on an AFM tip through a poly(ethylene glycol) (PEG) spacer, and the other dendron was anchored on a gold substrate as a self assembled monolayer. Two dendrons approached and then interacted with each other when the AFM tip and the substrate moved close together. The rupture force between dendrons was measured while the AFM tip and the substrate separated. PEG as a flexible spacer can function as a length window for recognizing the force signals and avoiding the disturbance of the interaction between the AFM tip and the substrate. The interaction between two first-generation dendrons is measured to be about 224 pN at a force loading rate of 40 nN/s. The interaction between second- and first-generation dendrons rises to 315 pN at the same loading rate. Such interactions depend on the force loading rate in the range of several to hundreds of nanonewtons per second, indicating that the rupture between dendrons is a dynamic process. The study of the interaction between surface-bound dendrons of different generations provides a model system for understanding the surface adhesion of molecules with multiple branches. In addition, this multiple-branch molecule may be used to mimic the sticky feet of geckos as a man-made adhesive. PMID- 17725374 TI - Color-changeable optical transport through Se-doped CdS 1D nanostructures. AB - The optical-transport properties of 1D Se-doped CdS nanostructures with different doping contents and/or crystallization degrees are reported. The locally excited photoluminescence shows a significant redshift during the transport along the long axis of the 1D structures and can leave enough PL intensity for detection. The magnitude of the redshift is found to be highly dependent on the content of doping and the crystallization degree. The experimental results are compared with theoretical calculations based on the fundamental absorption rule of the semiconductor, which demonstrates that the redshift is related to the optical reabsorption effects induced by the local structural disorder in the semiconductors. Such optical properties of 1D semiconductor structures might be of interest for potential applications in color-tunable nanosized light-emitting and/or frequency-converting devices. PMID- 17725375 TI - Intracellular delivery of quantum dots tagged antisense oligodeoxynucleotides by functionalized multiwalled carbon nanotubes. AB - With the goal of identifying an improved delivery scheme for intracellular tracking and anticancer therapy, we explored a novel double functionalization of a carbon nanotube delivery system containing antisense oligodeoxynucleotides (ASODNs) as a therapeutic gene and CdTe quantum dots as fluorescent labeling probes via electrostatically layer-by-layer assembling. This is the first time that we used mercaptoacetic acid-capped CdTe quantum dots as fluorescent labeling probes for clearly tracking the intracellular transport and evaluating delivery efficiency of ASODNs by functionalized multiwalled carbon nanotubes (MWNTs). PMID- 17725376 TI - Single-walled MoTe(2) nanotubes. AB - The structural, electronic, and mechanical properties of single-walled MoTe(2) nanotubes are investigated using density functional theory. All large-diameter MoTe(2) nanotubes are found to be narrow-gap semiconductors, whereas small diameter nanotubes are found to be less stable compared to large-diameter nanotubes. Notably, the armchair MoTe(2) nanotubes exhibit an indirect band gap, whereas the zigzag nanotubes exhibit a direct band gap. The band gap decreases with decreasing diameter of the tube or if the tube is under compression or elongation in the axial direction. Young's modulus of MoTe(2) nanotubes is calculated and is found to be dependent on the diameter and chirality of the tubes. The armchair nanotubes are stiffer than the zigzag nanotubes with the same diameter. Compared to the homologous MoTe(2) nanotubes, the MoTe(2) nanotubes are softer due to less strain-energy cost in forming the nanotube structures. PMID- 17725377 TI - Close-packed noncircular nanodevice pattern generation by self-limiting ion-mill process. AB - We describe a self-limiting, low-energy argon-ion-milling process that enables noncircular device patterns, such as squares or hexagons, to be formed using precursor arrays of uniform circular openings in poly(methyl methacrylate) defined using electron beam lithography. The proposed patterning technique is of particular interest for bit-patterned magnetic recording medium fabrication, where square magnetic bits result in improved recording system performance. Bit patterned magnetic medium is among the primary candidates for the next generation magnetic recording technologies and is expected to extend the areal bit density limits far beyond 1 Tbit/in(2). The proposed patterning technology can be applied either for direct medium prototyping or for manufacturing of nanoimprint lithography templates or ion beam lithography stencil masks that can be utilized in mass production. PMID- 17725378 TI - Low dietary riboflavin but not folate predicts increased fracture risk in postmenopausal women homozygous for the MTHFR 677 T allele. AB - The MTHFR C677T polymorphism is associated with mildly elevated homocysteine levels when folate and/or riboflavin status is low. Furthermore, a mildly elevated homocysteine level is a risk factor for osteoporotic fractures. We studied whether dietary intake of riboflavin and folate modifies the effects of the MTHFR C677T variant on fracture risk in 5,035 men and women from the Rotterdam Study. We found that the MTHFR C677T variant interacts with dietary riboflavin intake to influence fracture risk in women. INTRODUCTION: The MTHFR C677T polymorphism is associated with mildly elevated homocysteine (Hcy) levels in the presence of low folate and/or riboflavin status. A mildly elevated Hcy level was recently identified as a modifiable risk factor for osteoporotic fracture. We studied whether dietary intake of riboflavin and folate modifies the effects of the MTHFR C677T polymorphism on BMD and fracture risk. MATERIALS AND METHODS: We studied 5,035 individuals from the Rotterdam Study, >or=55 yr of age, who had data available on MTHFR, nutrient intake, and fracture risk. We performed analysis on Hcy levels in a total of 666 individuals, whereas BMD data were present for 4,646 individuals (2,692 women). RESULTS: In the total population, neither the MTHFR C677T polymorphism nor low riboflavin intake was associated with fracture risk and BMD. However, in the lowest quartile of riboflavin intake, female 677-T homozygotes had a 1.8 (95% CI: 1.1-2.9, p = 0.01) times higher risk for incident osteoporotic fractures and a 2.6 (95% CI: 1.3-5.1, p = 0.01) times higher risk for fragility fractures compared with the 677-CC genotype (interaction, p = 0.0002). This effect was not seen for baseline BMD in both men and women. No significant influence was found for dietary folate intake on the association between the MTHFR C677T genotype and fracture risk or BMD. In the lowest quartile of dietary riboflavin intake, T-homozygous individuals (men and women combined) had higher (22.5%) Hcy levels compared with C-homozygotes (mean difference = 3.44 microM, p = 0. 01; trend, p = 0.02). CONCLUSIONS: In this cohort of elderly whites, the MTHFR C677T variant interacts with dietary riboflavin intake to influence fracture risk in women. PMID- 17725379 TI - Fracture incidence in GH-deficient patients on complete hormone replacement including GH. AB - Fracture risk in GHD patients is not definitely established. Studying fracture incidence in 832 patients on GH therapy and 2581 matched population controls, we recorded a doubled fracture risk in CO GHD women, but a significantly lower fracture risk in AO GHD men. INTRODUCTION: The objective of this study was to evaluate fracture incidence in patients with confirmed growth hormone deficiency (GHD) on replacement therapy (including growth hormone [GH]) compared with population controls, while also taking potential confounders and effect modifiers into account. MATERIALS AND METHODS: Eight hundred thirty-two patients with GHD and 2581 matched population controls answered a questionnaire about fractures and other background information. Incidence rate ratio (IRR) and 95% CI for first fracture were estimated. The median time on GH therapy for childhood onset (CO) GHD men and women was 15 and 12 yr, respectively, and 6 and 5 yr for adult onset (AO) GHD men and women, respectively. RESULTS: A more than doubled risk (IRR, 2.29; 95% CI, 1.23-4.28) for nonosteoporotic fractures was recorded in women with CO GHD, whereas no risk increase was observed among CO GHD men (IRR, 0.61) and AO GHD women (IRR, 1.08). A significantly decreased incidence of fractures (IRR, 0.54; 95% CI, 0.34-0.86) was recorded in AO GHD men. CONCLUSIONS: Increased fracture risk in CO GHD women can most likely be explained by interaction between oral estrogen and the GH-IGF-I axis. The adequate substitution rate of testosterone (90%) and GH (94%) may have resulted in significantly lower fracture risk in AO GHD men. PMID- 17725380 TI - Effects of CD134 monoclonal antibody on hemolysis activities and expression of perforin in peripheral blood mononuclear cells of systemic lupus erythematosus patients. AB - Perforin had been demonstrated to play important roles in the pathology of systemic lupus erythematosus (SLE), which was a potential target of clinical treatment of SLE. CD134 was a member of the tumor necrosis factor receptor family, which had been demonstrated to inhibit expression of perforin mRNA. The aim of the present study was to determine the effects of CD134 monoclonal antibody (MAb) on expression and hemolysis activities of perforin and its mechanisms. Effects of CD134 MAb on hemolysis activities of perforin were measured by rabbit red blood cells. Effects of CD134 MAb on expression of perforin in peripheral blood mononuclear cells (PBMCs) were determined by reverse transcription-polymerase chain reaction (RT-PCR) method and flow cytometry. Then, expression of NF-kappaB P65 was detected by Western blot. The results showed that CD134 MAb could inhibit hemolysis activities and expression of perforin through decreasing expression of NF-kappaB P65. The inhibition effects were positively correlated to the SLE disease activity index (SLEDAI) and 24-hour protein-uria of SLE patients in active state. CD134 MAb is suggested to be a potential treatment for SLE patients. PMID- 17725381 TI - Production of monoclonal antibodies for detection of a secreted aspartyl proteinase from Candida spp. in biologic specimens. AB - Secreted acid proteinases (SAP) constitute an important group of virulence factors in Candida albicans. In the present work, an acid proteinase from C. albicans was sequentially purified from the supernatant of a yeast culture by precipitation with ammonium sulfate, ion exchange chromatography, and molecular exclusion chromatography, yielding a specific enzymatic activity of 204.1 IU/mg on bovine serum albumin (BSA). The molecular mass of the purified proteinase was estimated at 43 kd after exclusion chromatography and at 41 kd by nondenaturating sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The purified proteinase was able to degrade BSA at pH 2.5, but was not active on collagen, and it was significantly inhibited by pepstatin A. The immunization of BALB/c mice with the purified proteinase and later fusion of their spleen cells with myeloma cells resulted in 19 monoclonal antibody secreting hybridomas (MAbs) capable of detecting SAP in enzyme-linked immunosorbent assay (ELISA) assays. All MAbs obtained are isotype IgG1 kappa (kappa) immunoglobulins and develop a 41 kd protein band by Western blot (WB) in samples of SAP obtained from C. albicans (12 A) and C. dubliniensis (strain 778) crude extracts. The anti-SAP MAbs were used in capture ELISA and two combinations of these antibodies proved suitable for SAP detection, that is, MAP1 (1B1B3) or MAP2 (2D2C10) as coat antibodies, and biotinylated MAP3 (2A6E8) as detect antibody. Capture ELISA using these sets of MAbs detected over 32 ng/mL protein in purified SAP samples as well as in crude C. albicans and C. dubliniensis extracts. The results herein obtained allow for the prediction of how this set of antibodies can be useful for SAP detection in biologic specimens. PMID- 17725382 TI - Generation and characterization of murine monoclonal antibodies to genus-specific 31-kilodalton recombinant cell surface protein of Brucella abortus. AB - In the present study hybridomas were produced from fusion with splenocytes of BALB/c mice immunized with the recombinant 31-kDa cell surface protein (r31CSP) specific for Brucella species. A set of eight stabilized hybridoma cell lines was generated against r31CSP. Monoclonal antibodies (MAbs) produced by all these clones exhibited reactivity for r31CSP as well as with the protein of 31-kDa, derived from whole-cell lysate of 31-kDa Brucella abortus 544. Four of eight MAbs were IgG1, two IgG2b, and two IgM in nature. These MAbs did not show any cross reaction with whole-cell lysate of Yersinia enterocolitica O: 9, Vibrio cholerae, Salmonella typhimurium and Escherichia coli 0157 by Western blotting. Reactivity of these MAbs was further assessed with other organisms of Brucella species namely, B. abortus S99, B. canis, B. melitensis 16M, B. suis, and a clinical isolate of B. melitensis. Collectively, these data suggest that these MAbs may have the potential for use in the detection of Brucella species with high specificity. PMID- 17725383 TI - Production and characterization of monoclonal antibody against human serum albumin. AB - Hybridomas secreting monoclonal antibodies (MAbs) producing stable, specific and high affinity against human serum albumin (HSA) have been established. The aim of the present study was the production of MAbs that will be potentially used in designing immunoassay methods especially immunochromatography assay kit for screening of microalbuminuria (MAU) in the early detection of diabetic and nondiabetic nephropathy. The hybridomas were obtained by fusion of spleen cells from immunized mice with mouse myeloma cell line (SP2). After limiting dilutions three clones producing antibodies were designed as EMRC1-3, which displayed different pattern of fine specificity for HSA and low cross reaction with other proteins as elucidated by inhibition enzyme-linked immunosorbent assay (ELISA). These clones were found to be of immunoglobulin G (IgG) class with k light chain. Subclass determination showed that all three MAbs secreted IgG1 type of antibody. The results of affinity purification for the two selected clones (EMRC1 and EMRC3) displayed high affinity with no cross reactivity with any of the related protein molecules. The stable hybridomas secreting anti-HSA were expanded in 50 mL flasks for large-scale production of the required antibodies. The standard curves were constructed with a sensitivity of 10 pg per well covering up to 100 ng per well. The high binding activity to HSA antigen and having no cross reactivity with other related molecules illustrated the potential application of these antibodies as an immunodiagnostic reagent in designing an immunochromatography assay kit for screening of MAU in diabetic and nondiabetic patients. PMID- 17725384 TI - Epitope mapping of PR81 anti-MUC1 monoclonal antibody following PEPSCAN and phage display techniques. AB - PR81 is an anti-MUC1 monoclonal antibody (MAb) which was generated against human MUC1 mucin that reacted with breast cancerous tissue, MUC1 positive cell line (MCF-7, BT-20, and T-4 7 D), and synthetic peptide, including the tandem repeat sequence of MUC1. Here we characterized the binding properties of PR81 against the tandem repeat of MUC1 by two different epitope mapping techniques, namely, PEPSCAN and phage display. Epitope mapping of PR81 MAb by PEPSCAN revealed a minimal consensus binding sequence, PDTRP, which is found on MUC1 peptide as the most important epitope. Using the phage display peptide library, we identified the motif PD(T/S/G)RP as an epitope and the motif AVGLSPDGSRGV as a mimotope recognized by PR81. Results of these two methods showed that the two residues, arginine and aspartic acid, have important roles in antibody binding and threonine can be substituted by either glycine or serine. These results may be of importance in tailor making antigens used in immunoassay. PMID- 17725385 TI - Generation and characterization of mouse monoclonal antibody 5E1 against human transcription factor GLI3. AB - GLI3 is a transcriptional effector of the developmentally important hedgehog (Hh) signaling pathway. Here we report the production of mouse monoclonal antibody (MAb) against putative repressive motif in GLI3 (GLI3pRM). BALB/c mice were immunized with purified recombinant human GLI3pRM protein, and the splenocytes from these mice were fused with myeloma cell line (SP2/0) by using standard hybridoma production techniques. Resulting hybridomas producing anti-GLI3pRM antibodies were screened by enzyme-linked immunosorbent assay (ELISA) and isotyped. The specificity of MAb 5E1 was determined based on its activity in Western blot and immunofluorescence analyses of the human NT2/D1 cell line. The results showed that MAb 5E1 was immunoglobulin IgM/kappa, recognizing recombinant human GLI3pRM specifically. In addition, MAb 5E1 bound to the full-length (FL GLI3) as well as a short protein (GLI3R) and did not cross-react with a similar region in GLI2. MAb 5E1 could also be used to detect the expression of Gli3 in mouse cell lines and embryonic tissues. PMID- 17725386 TI - Production, characterization, and functional analysis of newly established CD99 monoclonal antibodies MT99/1 and MT99/2. AB - The leukocyte surface molecule CD99 is an integral membrane glycoprotein encoded by the E2/MIC2 gene. This molecule is broadly expressed on cells of the hematopoietic system and displays two surface forms, a long 32 kDa form and a short 28 kDa form. While the complete function of the CD99 molecule is unclear, it has been reported to be involved in regulation of cell adhesion, migration, and apoptosis. Thus, several CD99 monoclonal antibodies (MAbs) have been generated for biochemical and functional studies of the CD99 molecule. In the present study two CD99 MAbs, MT99/1 and MT99/2, were produced. The MAbs recognized different epitopes of the CD99 molecule. MAb MT99/1, but not MT99/2, was appropriate for biochemical characterization. Binding of MAb MT99/1 with its epitope led to the induction of cell adhesion and apoptosis. The generated MAbs can be used for future study of the function and mechanism of the CD99 molecule, including its role in the immune system, and may have application in tumor diagnosis and treatment. PMID- 17725387 TI - Creation and characterization of an IgG1-type monoclonal antibody against intact Aspergillus fumigatus conidia. AB - The inability to accurately mimic and track the natural mechanisms of sensitization, challenge, and clearance in experimental models of allergic asthma restricts the ability to identify potential therapeutic targets and elucidate basic biological mechanisms of this prominent human disease. Use of a clinically relevant fungal allergen, such as Aspergillus fumigatus, allows researchers to follow an allergen's uptake and clearance from the lung. Unfortunately, there are currently limited resources to specifically visualize or sensitively quantify a small number of fungal conidia in the lung. In this study, we have created and characterized an IgG1 isotype monoclonal antibody produced against the intact conidia of A. fumigatus for the purpose of developing specific detection and quantification techniques. PMID- 17725388 TI - Biochemical and histochemical characterization of the cattle V red blood cell antigen with monoclonal antibody IVA-41. AB - The cattle V antigen from the FV blood group system was characterized. Hemolytic as well as immunochemical analyses with monoclonal antibody (MAb) IVA-41 found that V antigen of bovine red blood cells is a membrane-bound, papain- and pronase sensitive, trypsin- and chymotrypsin-resistant N-glycosylated sialoglyco-protein with molecular weight of 64, 56, and 50 kDa under no reduction and 23 kDa under reduction conditions. In contrary to some human blood group antigens, the expression of bovine blood group V antigen is restricted to the erythrocyte membrane. PMID- 17725389 TI - Generation and characterization of monoclonal antibodies against tuberous sclerosis complex 2. AB - TSC1 and TSC2 are two recently identified tumor suppressor genes encoding hamartin and tuberin, respectively. They have been implicated in the pathogenesis of tuberous sclerosis, a neurological disorder linked with the development of hamartomas in numerous organs, including the brain, kidneys, heart, and liver. Both protein products of TSC1 and TSC2 form an intracellular complex exerting GTPase-activating (GAP) activity towards a small G protein Rheb (Ras homologue enriched in brain). Inhibition of Rheb is important for the positive regulation of mTOR pathway, while mutations of hamartin or tuberin result in uncontrolled cell cycle progression. Although the precise role for the TSC1/2 complex in tumor suppression is not clear, many studies have established a link with the regulation of transcription and protein biosynthesis, increasing susceptibility to apoptosis, cell differentiation, and cell cycle control. We describe the development of a monoclonal antibody specific towards TSC2/tuberin and characterize the suitability for Western blotting, immunoprecipitation, and immunofluorescent applications. The C-terminal region of TSC2 was expressed as a His-tag fusion protein in bacteria, affinity purified and used as an immunogen. Hybrid myelomas were produced from the spleenocytes of immunized mice and SP2/0 myeloma cells. Testing the specificity of cell culture supernatants from generated hybridomas towards recombinant His-TSC2C in ELISA assay allowed us to isolate a panel of positive clones. Further analysis of selected clones by Western blotting and immunoprecipitation revealed one clone, termed D6, which specifically recognized recombinant and endogenous TSC2. The specificity of generated antibody was also confirmed in TSC2(/) and TSC2(+/+) mouse embryo fibroblasts. In summary, the produced antibody is a useful tool in our research program and will be available for researchers investigating signal transduction pathways involving TSC1/2 signaling under physiological conditions and in human pathologies. PMID- 17725400 TI - Levinas, Winnicott, and therapy. PMID- 17725399 TI - "You are, therefore I am": Emmanuel Levinas and psychoanalysis. PMID- 17725401 TI - "The talking cure": the ethics of psychoanalysis. PMID- 17725402 TI - "What Levinas and psychoanalysis can teach each other, or how to be a mensch without going Meshugah". PMID- 17725403 TI - Is Levinas relevant to psychoanalysis? PMID- 17725404 TI - An analysis of the psyche inspired by Emmanuel Levinas. PMID- 17725405 TI - "I'm just wild about Harry!" a psychoanalyst reflects on his relationship with his dog. PMID- 17725406 TI - Can Levinas's ethical metaphysics contribute to psychoanalysis? The case for and against. PMID- 17725407 TI - Levinas and psychoanalysis: the radical turn outward and upward. PMID- 17725409 TI - Treating the genetic make-up of breast cancer: a new fashion? PMID- 17725410 TI - E1A- and E1B-Double mutant replicating adenovirus elicits enhanced oncolytic and antitumor effects. AB - Gene-modified replication-competent adenoviruses (Ads) are emerging as a promising new modality for the treatment of cancer. We have previously shown that E1B 19kDa and E1B 55kDa gene-deleted Ad (Ad-DeltaE1B19/55) exhibits improved tumor-specific replication and cell lysis, leading to an enhanced antitumor effect. In an effort to increase cancer cell selectivity of a replicating adenovirus, we first generated 11 E1A mutant Ads (Ad-E1mt1 to Ad-E1mt11) with deletion or substitution in retinoblastoma (pRb)-binding sites of E1A. Of these, Ad-E1mt7 demonstrated significant improvement in cytopathic effect (CPE) and viral replication in a cancer cell-specific manner. To further enhance the cancer cell specificity of Ad-E1mt7, Ad-DeltaE1Bmt7 was generated, in which both the E1B 19kDa and E1B 55kDa genes were deleted. As assessed in CPE assay and immunoblot analysis for Ad fiber expression, Ad-DeltaE1Bmt7 exerted marked enhancement in cancer cell-specific killing as well as viral replication in comparison with its comparative controls (Ad-E1mt7, Ad-DeltaE1B55). Furthermore, the growth of established human cervical carcinoma in nude mice was significantly suppressed by intratumoral injection of Ad-DeltaE1Bmt7. In summary, we have developed an oncolytic adenovirus with a significantly improved therapeutic profile for cancer treatment. PMID- 17725411 TI - Genetic polymorphisms and resistance mutations of HIV type 2 in antiretroviral naive patients in Burkina Faso. AB - Natural polymorphisms in the pol gene of HIV-2 may influence the susceptibility to antiretroviral drugs and the choice of treatment. We collected samples in centers for anonymous HIV testing in Ouagadougou, Burkina Faso, in patients supposedly naive for any antiretroviral treatment. Eighty-four samples were first tested as HIV-2 positive in Burkina Faso and then shipped to Brussels, Belgium, for confirmation of the serological status and plasma viral load. Fifty-two samples were confirmed as HIV-2 positive in Belgium. Twelve others were HIV-1 positive and 20 were dually reactive. Twenty-one of HIV-2 confirmed samples had an HIV-2 plasma viral load higher than 1000 copies/ml. These viruses were sequenced in the protease and reverse trancriptase genes and 17 sequences of the pol gene were obtained. Highly polymorphic positions were identified in protease and RT genes. Two samples harbored known resistance mutations: M184V RT mutation in one and Q151M with M184V in the other. Phylogenetic analysis showed that viruses in Burkina Faso did not cluster separately from published sequences from neighboring countries. The two resistant strains were unrelated. Our findings imply either that resistant viruses are circulating in Burkina Faso or that some individuals take unsupervised treatment. Both hypotheses present problems. PMID- 17725412 TI - Evolution of cervical cytologic changes among HIV-infected women with normal cytology in the HAART era. AB - The influence of HAART on the evolution to cervical squamous intraepithelial lesions (SIL) among HIV(+) women with a normal cytological test in the HAART era was studied. A retrospective cohort study (1997-2005) of HIV-infected women treated with HAART was conducted. Those with a normal cervical cytology (Papanicolaou test) and at least one subsequent test were included. Survival (time until diagnosis of SIL), univariate, and multivariate analyses were performed. A total of 133 HIV-infected patients treated with HAART were included. The incidence of SIL was 35% (47 patients). SIL was diagnosed in 36 of 110 (33%) patients with a baseline and final immunological status of >200 CD4 cells/microl and in 6 of 9 (67%) patients with a baseline and final immunological status of < or =200 CD4 (OR: 0.24, 95% CI: 0.06-1.03, p = 0.041). SIL was diagnosed in 10 of 60 (17%) patients with an undetectable baseline and final HIV viral load and in 36 of 70 (51%) patients with a detectable HIV viral load (OR: 0.19, 95% CI: 0.07 0.46, p < 0.001). A high incidence of SIL (cancer precursor lesions) was observed among HIV(+) women without a background of cervical pathology. The effect of HAART on the control of HIV replication and of immunological status (>200 CD4) through the follow-up was associated with a reduction of SIL. PMID- 17725413 TI - Role of weight-based ribavirin dosing and extended duration of therapy in chronic hepatitis C in HIV-infected patients: the PRESCO trial. AB - The response to pegylated interferon (pegIFN) plus ribavirin (RBV) as treatment of chronic hepatitis C virus (HCV) infection is lower in HIV-coinfected than in HCV-monoinfected patients and could be due to suboptimal RBV dosing and/or insufficient duration of therapy in prior trials. In a prospective, multicenter, open, comparative trial, HCV/HIV-coinfected patients received pegIFN plus weight based RBV for 48 or 72 weeks (HCV genotypes 1 and 4) and 24 or 48 weeks (HCV genotypes 2 and 3). Use of didanosine was not allowed. Out of 389 patients included in the trial, 61% were infected by HCV-1/4 and 67% had serum HCV-RNA >500,000 IU/ml. Sustained virological response (SVR) was achieved by 49.6%, significantly higher in HCV-2/3 than HCV-1/4 (72.4% vs. 35%; p < 0.0001). A high drop-out rate in the longer treatment arms precluded obtaining definitive conclusions about the efficacy of prolonging therapy. Premature treatment discontinuations due to serious adverse events occurred in 8.2%. Infection with HCV-2/3, lower baseline HCV-RNA, and negative HCV-RNA at week 12 were all independent predictors of SVR in the multivariate analysis. The use of RBV 1000 1200 mg/day plus pegIFN is relatively safe and provides SVR in nearly half of coinfected patients, twice as high in HCV-2/3 than HCV-1/4. PMID- 17725414 TI - No observable correlation between central nervous system side effects and EFV plasma concentrations in Japanese HIV type 1-infected patients treated with EFV containing HAART. AB - The present study assessed the relationship between central nervous system (CNS) side effects and plasma concentrations of efavirenz (EFV) in Japanese HIV-1 infected patients. Subjects consisted of 69 HIV-1-infected patients (57 therapy naive and 12 therapy-experienced patients) being treated using EFV in combination with other antiretroviral agents at the outpatient HIV clinic. Successful virological treatment was achieved in 61 patients. Eight patients discontinued EFV containing therapy because CNS symptoms did not resolve (four patients), EFV specific mutations were detected (two patients), or skin rash was observed (two patients). Mean EFV plasma concentration for 61 effectively treated patients, measured at 15 h postdosing, was 2.42 microg/ml (range: 0.78-6.82 microg/ml). This EFV concentration range contributed to suppressed viral load in these Japanese patients. Adverse CNS effects were observed in 19 patients soon after therapy onset. These effects disappeared within 1 month except for four patients who suffered severe CNS side effects. Mean EFV plasma concentrations were not significantly different between subjects with (2.45 +/- 1.08 microg/ml) and without (2.42 +/- 1.40 microg/ml) CNS side effects. We concluded no correlation existed between the plasma EFV concentration and the emergence of CNS side effects in Japanese HIV-1-infected patients. Further investigations, enforced with the drug concentration measurement at earlier time points and more appropriate assessment of CNS symptoms, are required. PMID- 17725415 TI - Baseline genotype as a predictor of virological failure to emtricitabine or stavudine in combination with didanosine and efavirenz. AB - The presence of drug-associated mutations among ART-naive, HIV-1(+) patients may compromise the response to antiviral therapy. We evaluated the effect of preexisting drug-associated resistance mutations to the response in treatment naive patients to therapy with emtricitabine (FTC) or stavudine (d4T) in combination with didanosine (ddI) and efavirenz (EFV). Study FTC-301A compared emtricitabine once daily (QD) with stavudine twice daily in combination with didanosine and efavirenz in ART-naive patients. Genotypic analysis was performed on baseline plasma HIV-1 RNA for all available samples and at time of virologic failure (VF). Drug resistance mutations present at baseline were evaluated as predictors of VF using logistic regression. VF rates were compared between subgroups using a two-sided exact test. Baseline drug resistance mutations were observed in 90/546 (16.5%) patients: 56/90 (62.2%) with nonnucleoside analogue (NNRTI) mutations and 42/90 (46.6%) with nucleoside analogue mutations. In a stepwise, multiple regression analysis, the presence of the K103N mutation at initiation of therapy was associated with VF in both arms (p = 0.001), however, there was a higher incidence of VF in the stavudine arm compared to the emtricitabine arm regardless of the presence or absence of mutations at baseline (p = 0.001). In this study, the presence of drug-associated resistance mutations in ART-naive patients was significantly correlated with subsequent development of virologic failure underscoring the utility of testing for resistance in addition to the use of potent and well-tolerated first line regimens in treatment-naive patients. PMID- 17725416 TI - Effects of HIV type 1 infection on hematopoiesis in Botswana. AB - Clinical observations suggest that HIV-1 infection causes higher anemia rates in patients in southern Africa than in those in the United States. To explore this difference we performed a cross-sectional exploratory study on the effect of HIV 1 infection on hematopoiesis in Botswana by examining hematological presentation, HIV disease state, hematopoietic progenitor cell number, and circulating viral levels in HIV-infected patients and HIV-uninfected controls. We found significant associations between CD34(+) and CD4(+) cell counts in HIV-positive patients. Significant relationships were also seen between the CD34(+) CD4(+) cell population and hemoglobin levels, as well as colony-forming ability. These associations, however, were not seen in uninfected controls. Circulating viral p24 levels were found to correlate significantly with CD34(+) cell count, CD34(+) CD4(+) cell count, and colony-forming ability. These results demonstrate a direct association between HIV-1 infection in southern Africa and hematopoietic progenitor cell health. PMID- 17725417 TI - Morphine-mediated deterioration of oxidative stress leads to rapid disease progression in SIV/SHIV-infected macaques. AB - Oxidative stress is well documented in HIV infection, but the effect of concomitant substance abuse is largely unknown. We studied oxidative stress in our macaque model of morphine abuse and AIDS. In plasma, we found an approximately 50% decrease in catalase activity with morphine dependence that was exacerbated by infection in rapid progressors. Superoxide dismutase was decreased by a similar degree, but only in the presence of both morphine and viral infection. The loss of these antioxidant systems was coincident with significantly increased plasma malondialdehyde upon viral infection that displayed a synergistic increase in conjunction with morphine and rapid disease. PMID- 17725419 TI - The complexity of circulating HIV type 1 strains in Oyo state, Nigeria. AB - Multiple HIV-1 subtypes and circulating recombinant forms (CRFs) are known to circulate in West Africa. We undertook a survey of HIVs in Oyo state, in southwestern Nigeria. We analyzed 71 samples from Ibadan, the capital city, and 33 samples from Saki, 100 miles west of Ibadan. We sequenced part of the gag gene and the envelope C2V3 region from 102 and 89 samples, respectively. In the 87 samples for which both genes were sequenced, subtype G and CRF02_AG were found in equal proportions (32.2% each). Other samples included CRF06_cpx (8.0%), subtype A (2.3%), C (1.1%), unclassified (1.1%), or discordant sequences suggesting the presence of a large number of recombinants involving CRF02_AG and/or subtype G (20.7%) or other subtypes (2.3%). The subtype/CRF designation was concordant in two gene fragments in the majority of samples evaluated. However, we observed differences in subtype distribution between the two locations with a predominance of subtype G in Ibadan and CRF02 in Saki. This is the first in-depth analysis of HIV variability at a state level in Nigeria. Our analysis revealed a significant level of viral heterogeneity and a geographical difference in subtype distribution, and demonstrated that CRF02_AG does not account for the majority of circulating strains. PMID- 17725418 TI - Identification of a novel circulating recombinant form (CRF) 36_cpx in Cameroon that combines two CRFs (01_AE and 02_AG) with ancestral lineages of subtypes A and G. AB - An array of CRFs have been identified in Cameroon, the most notable being CRF02_AG. HIV-1 in the East Province of Cameroon is particularly diverse: in a recent study, we found a high proportion of unique recombinant forms (URFs). Herein we describe the analysis of the full-length sequences of two of these URFs, which, after preliminary analysis of gag, pol, and env fragments, appeared to be a novel CRF. This novel strain, CRF36_cpx, contains fragments that can be assigned to the CRF01_AE, CRF02_AG, and subtype A and G radiations. Forty percent of the genome can be classified as CRF02_AG, including regions in gag, pol, env, and the accessory genes. Twenty-seven percent is CRF01_AE, comprising the majority of gag, the beginning of env, and the end of env into the 3' LTR. Twenty percent of the genome can be assigned to subtype A, with segments in pol and env. The remaining 13% of the sequence is classifiable as subtype G, in pol and vpu. The subtype A and G lineages formed by the CRF36_cpx sequences are unique and appear ancestral in nature. CRF36_cpx is both the first to combine more than one CRF and the first to include fragments of CRF02_AG. The ancestral sequences present in CRF36_cpx represent a link to extinct strains, and, potentially, insight into the evolution of HIV-1. PMID- 17725420 TI - Polymorphisms of Cx(3)CR1 and CXCR6 receptors in relation to HAART therapy of HIV type 1 patients. AB - The chemokine polymorphisms CXCR6-3E/K, In1.1T/C, H7 haplotype, CX(3)CR1-V249I, and CX(3)CR1-T280M have been shown to affect the course of HIV infection. We studied their influence on immunologic and virologic response to HAART in a group of 143 HIV-1 patients. We performed Kaplan-Meier analysis using the following end point criteria: (1) time from HAART initiation to undetectable viral load (VL < 50 copies/ml), (2) maximum duration of viral suppression, (3) time from HAART administration until CD4 elevation above 200 cells/microl for patients with baseline CD4 below 200 cells/microl and above 500 cells/microl for patients with baseline CD4 between 200 and 500 cells/microl, respectively, and (4) time from HAART initiation until CD4 reduction below baseline values. Our results revealed an improved immunologic response to HAART in patients with the CX(3)CR1-249I or CX(3)CR1-280M allele. On the contrary, patients with initial VL suppression due to HAART showed a faster virologic failure in the presence of the CXCR6-3K allele. The In1.1T/C polymorphism and H7 haplotype did not reveal any specific effect on HAART response. PMID- 17725422 TI - The major 5' end of HIV type 1 RNA corresponds to G456. AB - In the course of studies on HIV-1 RNA structure, we determined that the main 5' end of viral RNA from virions and virus producer cells corresponds to G456 in the proviral DNA sequence, one or two nucleotides down-stream from the reported ends that correspond to G454 and G455. We mapped 5' ends using the highly accurate RNA ligase-mediated rapid amplification of cDNA ends (RLM-RACE) method. The reactivity of the 5' ends indicates that they are mainly capped, although the presence of some uncapped (5'-triphosphorylated) RNA cannot formally be excluded. When we used a 5' mapping method susceptible to incorporating a cytosine at the 3' end of cDNA first strands, at a position templated by the 7-methylguanosine cap, 50% of clones derived from virion RNA had incorporated the additional cytosine. Reassignment of the 5' end has consequences for the design of short RNAs used to study HIV-1 RNA structural dynamics. PMID- 17725421 TI - CTL response to HIV type 1 subtype C is poorly predicted by known epitope motifs. AB - Cytotoxic T lymphocyte (CTL) responses are thought to be essential for the control of HIV-1 replication in vivo and immunogens that elicit CTL responses are currently a major focus of HIV vaccine research. Here we investigated two aspects of the CTL response to HIV-1 subtype C that are important for vaccine design and efficacy monitoring. First, we assessed the relationship between the CTL response and sequence diversity, using a robust statistical method. While peptides that were most frequently recognized by the CTL response in Nef and p24 tended to be conserved, this was not the case for p17 where epitope recognition coincided with highly variable regions. Second, we investigated the relationship between observed and predicted CTL responses, given the HLA genotype of infected individuals. Only 52% of the Nef peptides and 64% of the Gag peptides that elicited a CTL response contained sequence motifs thought to be required for binding by the HLA-A or -B alleles found in the corresponding patient. In a comparable subtype B dataset a much higher proportion of the peptides that elicited a CTL response were consistent with the patient HLA genotype (96% and 83% for Nef and Gag, respectively). We demonstrate that this difference between subtypes C and B is likely to result from a combination of a tendency for HLA alleles common in Southern African populations to be poorly characterized, as well as a tendency for sequence motifs associated with HLA recognition to be overspecified for sequence variation found in the B clade. Our results suggest that knowledge of HLA binding motifs is likely to be biased toward certain populations and subtypes. This can have important implications for understanding immune escape and predicting vaccine efficacy in the context of populations primarily infected with non-B subtype HIV-1. PMID- 17725423 TI - Genetic characterization of three newly isolated CRF07_BC near full-length genomes in China. AB - Though HIV-1 CRF07_BC rapidly spread in China, there have been few reports about this subtype since its first genetic characterization nearly 10 years ago. It was urgent and necessary to know the current gene variation of circulating CRF07_BC strains. Xinjiang was the main region for the CRF07_BC epidemic and also an ideal region for research on the viral gene evolution. The strains of Ulumuqi and Yili in Xinjiang were isolated, cloned, and sequenced in this study. Analyses of phylogenetic, potential CTL epitopes and N-glycosites were preformed simultaneously. New CRF07_BC isolates showed higher genetic diversity and more potential N-glycosites than old isolates. It was interesting that although the env and nef genes are highly variable, highly conserved potential CTL epitopes and N-glycosites were found in deduced gp120 V3 and Nef product of all CRF07_BC isolates. The analysis of the sequences provides some valuable information on the investigation of the epidemiology and on vaccine development. PMID- 17725424 TI - Drug resistance in plasma and breast milk after single-dose nevirapine in subtype C HIV type 1: population and clonal sequence analysis. AB - Single-dose nevirapine (SD NVP) reduces intrapartum HIV-1 transmission, but nonnucleoside reverse transcription (NNRTI) resistance mutations can emerge. Population sequencing among 32 subtype C HIV-1-infected, SD NVP-exposed Zimbawean women demonstrated NNRTI resistance in 25/32 (78%) women: 23/30 (77%) at 2 weeks, 11/31 (35%) at 8 weeks, and 5/27 (19%) at 24 weeks. A total of 447 unique TA clones (median = 28 per time point), from four women with resistance at 8 weeks but wild-type virus by population sequence at 24 weeks, identified NNRTI mutations in a median of 76% (range: 55-96%) of individual clones at 2 weeks, 48% (range: 33-80%) at 8 weeks, and 5% (range: 0-15%) by 24 weeks. NNRTI mutations in breast milk clones at 2 and weeks from one woman varied significantly from plasma. Population sequencing underestimates the diversity of NNRTI resistance mutations within minority populations following SD NVP in subtype C HIV-1 viral RNA in plasma and breast milk. PMID- 17725425 TI - Genotypic analysis of the protease and reverse transcriptase of HIV type 1 isolates from recently infected injecting drug users in western China. AB - The partial pol gene was analyzed to determine circulating HIV-1 subtypes and the prevalence of drug resistance among recently infected injecting drug users in the west of China. Phylogenetic and bootscanning analyses showed that all 25 sequences belonged to CRF07_BC. No major drug resistance mutations were found, while the CRF07_BC sequences harbored a few highly prevalent polymorphic positions in both the protease and reverse transcriptase regions. It is notable that D60E, L63P and I93L substitutions, which were more common in HIV-1 isolates from PI-treated than untreated patients, were present in most of the isolates. Compared with subtype B, the CRF07_BC strains had a decreased genetic barrier for the V106M mutation, which is selected by efavirenz and leads to high-level resistance to all present nonnucleoside RT inhibitors. Further studies are needed to determine the impact of genetic features of CRF07-BC on antitretroviral susceptibility and evolution of drug resistance mutations. PMID- 17725427 TI - Time for the American Thyroid Association to lead on thyroid screening in pregnancy. PMID- 17725428 TI - Molecular interactions between the TSH receptor and a Thyroid-stimulating monoclonal autoantibody. AB - OBJECTIVE: To study the molecular interactions between the thyroid-stimulating hormone (TSH) receptor (TSHR) and a human thyroid-stimulating monoclonal autoantibody (M22). DESIGN: Amino acid mutations were introduced in the variable region gene sequences of M22 and the wild-type (WT) or mutated M22 Fab expressed in Escherichia coli. The ability of WT or mutated M22 Fab to inhibit binding of (125)I-TSH or (125)I-M22 to the TSHR and to stimulate cyclic adenosine monophosphate (AMP) production in Chinese hamster ovary cells expressing WT TSHRs was studied. Mutated TSHRs were also used in these studies in combination with WT or mutated M22 Fab to further identify interacting residues in the TSHR-M22 complex. MAIN OUTCOME: Out of 11 amino acid changes in the heavy chain (HC) of M22, 7 had an effect on M22 Fab biological activity, while in the case of 1 mutation the Fab was not expressed. In particular, stimulating activity of M22 Fab mutated at HC residues, D52, D54, and Y56 was markedly reduced. Mutation of M22 light chain (LC) D52 also reduced M22 Fab stimulating activity, while mutations at two further residues (LC D51 and LC D93) showed no effect. Reverse charge mutations at M22 HC D52 and TSHR R80 provided experimental evidence that these two residues interacted strongly with each other. CONCLUSION: Mutation of both the TSHR and M22 Fab has allowed identification of some residues critical for the receptor-autoantibody interaction. This approach should lead to detailed mapping of the amino acids important for M22 biological activity. PMID- 17725429 TI - Molecular and genotypic characterization of human thyroid follicular cell carcinoma-derived cell lines. AB - OBJECTIVE: Our aim was to characterize the molecular and genotypic profile of eight thyroid carcinoma-derived cell lines-TPC1, FB2, B-CPAP, K1, XTC-1, C643, 8505C, and Hth74-in order to use them as in vitro models of thyroid carcinogenesis. DESIGN: We evaluated the expression of five thyroid-specific genes (Tg, TSHr, TPO, PAX8, and TTF-1) to establish the cell lineage and to assess the differentiation status of each of the cell lines. We screened for mutations in the most relevant oncogenes/tumor suppressor genes affected in thyroid carcinogenesis: RAS, BRAF, CTNNB1, and TP53 along with RET/PTC rearrangements. Considering the putative relevance in general carcinogenesis, we have also studied other molecules such as EGFR, PI3K, RAF-1, and THRB. To determine the genetic identity of the cell lines, we performed genotypic analysis. MAIN OUTCOME: The panel of cell lines we have studied displayed activation of several oncogenes (BRAF, RAS, RET/PTC) and inactivation of tumor suppressor genes (TP53) known to be important for thyroid carcinogenesis. Two of the cell lines-TPC1 and FB2-shared the same genotypic profile, probably representing clones of an ancestor cell line (TPC1). CONCLUSION: Due to their different molecular alterations, these cell lines represent a valuable tool to study the molecular mechanisms underlying thyroid carcinogenesis. We suggest that genotypic analyses should be included as a routine procedure to guarantee the uniqueness of each cell line used in research. PMID- 17725430 TI - Thyroid autoimmunity in the current iodine environment. AB - Iodine is essential for thyroid function. Thyroid disorders related to iodine deficiency decreased progressively with the continuous iodine prophylaxis and the increased iodine intake. An adverse effect resulting from iodine prophylaxis may be the induction of thyroid autoimmunity. Although experiments performed in animal models suggest that iodine could initiate or exacerbate thyroid autoimmunity, the role of iodine in humans remains controversial. Several observational studies in areas with adequate or high iodine intake suggest that there is an increase in the incidence of thyroid autoimmune disease. Moreover, intervention studies suggest that increased iodine intake may enhance thyroid autoimmunity too. However, not all studies generated the same findings, probably because of genetic, racial, and environmental differences. It seems that autoimmune exacerbation is a transient phenomenon. Studies have shown that in persons presenting thyroid antibodies, the levels of these antibodies progressively decrease when the majority of them react against a nonspecific pattern of thyroglobulin (Tg) epitopes. However, in a small number of these persons, the anti-Tg antibodies are similar to those in patients with patent thyroid autoimmune disease, reacting against specific immunodominant Tg epitopes, and their levels persist. One possible attractive explanation is that enhanced iodine intake increases the antigenicity of Tg through the incorporation of iodine into its molecule and the formation of iodinated Tg epitopes or even the generation of noniodinated pathogenetic Tg epitopes that are normally cryptic. PMID- 17725431 TI - Cigarette smoking and iodine as hypothyroxinemic stressors in U.S. women of childbearing age: a NHANES III analysis. AB - BACKGROUND: Exposure to environmental thiocyanate through smoking has been suggested to lead to hypothyroxinemia, which potentially impairs brain development in the fetuses of affected women, though studies are conflicting. It was hypothesized that iodine status might modulate the effects of thiocyanate exposure on the prevalence of hypothyroxinemia in women of childbearing age. DESIGN: The study population comprised 6967 women (age range: 15- 44 years) from the National Health and Nutrition Examination Survey (NHANES) III database. Smoking status was stratified into nonsmokers and those who smoked 1-10, 11-20, 21-30, and 31+ cigarettes a day. Iodine status was stratified based on urinary iodine excretion as <50, 50-99, 100-199, 200-299, and 300+ microug/L. Hypothyroxinemia was defined as the lower fifth percentile of total thyroxine levels among nonsmokers, adjusted for age and race/ethnicity. Univariate, multivariate, and regression analyses were conducted to evaluate the impact of smoking and urinary iodine excretion on the prevalence of hypothyroxinemia. RESULTS: Increasing levels of cigarette smoking are associated with increasing prevalence of hypothyroxinemia [chi(2)(4) = 14.15, p = 0.007]. When analyzed by urinary iodine level, the hypothyroxinemic effect of smoking was limited to the highest two urinary iodine strata [chi(2)(4) = 41.48, p < 0.001; and chi(2)(4) = 40.62, p < 0.001]. A significant interaction effect between smoking and urinary iodine was noted, underscoring the relationship between high levels of urinary iodine excretion and smoking with respect to hypothyroxinemia. CONCLUSIONS: Heavy smoking was associated with a higher prevalence of hypothyroxinemia. The impact of thiocyanate exposure from smoking on the prevalence of hypothyroxinemia is limited to those women of childbearing age with the highest urinary iodine excretion. Iodine supplementation should be cautiously considered in women of childbearing age who are smokers. PMID- 17725432 TI - Thyroid disease and pregnancy: degrees of knowledge. AB - OBJECTIVE: The literature on the impact of thyroid abnormalities on pregnancy and the postpartum has expanded rapidly over the last two decades. The objective of the present study was to determine the level of knowledge of endocrinologists, obstetrician/gynecologists, internists, and family physicians in regard to thyroid disease and pregnancy. DESIGN: A 16-item questionnaire on issues related to thyroid disease and pregnancy was developed. Endocrinologists (n = 116), obstetrician/gynecologists (n = 81), internists (n = 109), and family physicians (n = 99) were asked to complete the questionnaire. Physician self-report of confidence regarding degree of knowledge was obtained through completion of a seven-point Likert scale. MAIN OUTCOME: The percentage of questions answered correctly by all physicians was 63%. Endocrinologists had the highest correct response rate (77%), followed by obstetrician/gynecologists. Hierarchical regression analysis revealed that medical specialty, years of training, confidence level, and whether or not the physician treated pregnant women were significantly related to the overall score. CONCLUSIONS: The present study demonstrates a suboptimal level of knowledge regarding thyroid disease and pregnancy among physicians in four specialties. A comprehensive physician education program is needed. PMID- 17725433 TI - A dietary iodine questionnaire: correlation with urinary iodine and food diaries. AB - OBJECTIVE: It has been difficult to determine the sources of U.S. dietary iodine. This study was designed to validate a self-administered questionnaire about dietary iodine sources. DESIGN: We constructed a questionnaire to assess iodine intake in 46 healthy Boston-area adult volunteers. Questionnaire information was correlated with subjects' 24-hour food diaries. Spot morning urine cotinine (a metabolite of nicotine from cigarette smoking) and iodine concentrations were measured. MAIN OUTCOMES: 91% of 46 subjects were women [mean (+/- SD) age of 38 (+/- 10) years]. Information from 24-hour food diaries correlated well with questionnaire data. The median urinary iodine concentration (UIC) was 140 microg/L (range: 18-845 microg/L). There were significant positive associations between intake of yogurt (n = 9, p = 0.01) and saltwater fish (n = 6, p = 0.0003), and an inverse correlation between bagels (n = 5, p = 0.0006) and UIC. We found no associations between self-reported milk, iodized salt, tobacco use, or urinary cotinine and UIC. CONCLUSION: The questionnaire may not have been sufficiently comprehensive. Given the importance of adequate dietary iodine intake, particularly among women of childbearing age, further studies are warranted to determine important sources of dietary iodine in the United States. PMID- 17725434 TI - New medications which decrease levothyroxine absorption. AB - OBJECTIVE: Medications may sometimes interfere with the intestinal absorption of levothyroxine, primarily by forming an insoluble complex with the thyroid hormone in the intestinal lumen. The goal of this study was to examine the acute effects of three previously unstudied medications on levothyroxine absorption. DESIGN: We studied the effects of three medications on thyroxine absorption in seven normal volunteers. On each study day, the subjects ingested 1 mg levothyroxine sodium, either taken separately or co-administered with sevelamer hydrochloride (Renagel, a phosphate-binding medication used in the treatment of hyperphosphatemia), chromium picolinate (an over-the-counter nutritional supplement), or ezetimibe (Zetia, a drug used in the treatment of hypercholesterolemia). Serum thyroxine was measured at intervals over a 6-hour period following drug ingestion. MAIN OUTCOME: Sevelamer hydrochloride and chromium picolinate each significantly (p < 0.05) decreased the area under the serum thyroxine concentration curve, while ezetimibe had no effect. CONCLUSION: Hypothyroid patients taking sevelamer hydrochloride or chromium picolinate should be advised to separate the time of ingestion of these drugs from their thyroid hormone preparation by several hours. PMID- 17725435 TI - The effect of infertility medication on thyroid function in hypothyroid women who conceive. AB - OBJECTIVE: To determine whether infertility medications alter thyroid status in patients with treated hypothyroidism, and whether resulting pregnancies require additional thyroid supplementation compared with those conceived spontaneously. DESIGN: Prospective observational study of 18 infertility patients with treated hypothyroidism who conceived between July 2005 and July 2006 with or without infertility medications. Thyroid studies were performed prior to conception, at the time of pregnancy diagnosis, and approximately 6 weeks after an increase in thyroid replacement dose. MAIN OUTCOME: Orally medicated conceptions were similar to spontaneous conceptions on all thyroid related variables, and therefore the two groups were combined for analysis. Although there was a nonsignificant difference in thyrotropin (TSH) levels postconception (3.8 mIU/L vs. 2.2 mIU/L, p = 0.30), there was no difference in TSH levels after increase in thyroid replacement dose (1.7 mIU/L vs. 1.1 mIU/L, p = 0.30) between patients who conceived after gonadotropin stimulation compared with those who conceived spontaneously or with oral medications. The mean percent dose increases for the nongonadotropin and gonadotropin pregnancy groups were 30.6% and 32.4%, respectively. CONCLUSIONS: Hypothyroid patients who conceive after gonadotropin stimulation or with oral medications for ovulation induction do not need additional thyroid supplementation compared with those who conceive spontaneously. PMID- 17725436 TI - Seymour D. Van Meter, M.D. (1865-1934): the Texan who wielded a scalpel in Denver and left a lasting legacy. PMID- 17725437 TI - Preoperative embolization of thyroid arteries in a patient with a large cervicomediastinal hyperfunctioning goiter. AB - We present the case of a 61-year-old male patient with chronic obstructive pulmonary disease and a large cervicomediastinal multinodular hyperfunctioning goiter that made thyroidectomy a daunting task, especially considering the risk of intraoperative bleeding. The preoperative computed tomographic (CT) scan showed the right thyroid lobe very deeply rooted in the mediastinum, below the horizontal plane passing through the aortic arch. The thyroid mass imprinted the arterious and venous innominate trunks. To avoid a median sternotomy and remove the enlarged thyroid through a cervical approach alone, we decided to reduce the goiter in volume preoperatively by embolizing the thyroid arteries. We embolized the superior and inferior left, and the inferior right thyroid arteries. We spared the superior right thyroid artery because its blood supply contributed little to thyroid perfusion. After embolization, the patient was treated with antithyroid agents and corticosteroid drug therapy. At the same time, severe leukocytosis developed, thyroid hormone values increased, and a CT scan obtained 7 days after embolization showed the thyroid unchanged in volume. We therefore discharged the patient and were waiting for his laboratory blood chemical findings to return to normal. Thirty days later the patient was readmitted to hospital, and a new CT scan showed that the thyroid mass had diminished to half its initial volume. We could therefore perform a total thyroidectomy through a cervical approach alone. The only problem arose in dissecting tight right inferior laryngeal nerve adhesions to the thyroid capsule, probably sequelae of postembolization thyroiditis. Even though preoperative thyroid-artery embolization cannot be considered a routine technique in cervicomediastinal goiter surgery, in a rare patient who presents with a voluminous goiter such as the one we describe here, it is a useful procedure. PMID- 17725438 TI - Rifampin-induced hypothyroidism without underlying thyroid disease. AB - Rifampin (RFP) increases hepatic microsomal enzyme activity, and there are case reports of RFP-induced hypothyroidism, all associated with Hashimoto's thyroiditis. Here, we report a case of RFP-induced hypothyroidism without underlying thyroid disease. PMID- 17725439 TI - Parathymic parathyroid adenoma. PMID- 17725440 TI - Metastatic papillary thyroid carcinoma presenting as a long-standing calcified neck mass. PMID- 17725441 TI - A patient with asymmetric parotid uptake on a diagnostic iodine-131 scan during thyroid cancer follow-up. PMID- 17725443 TI - [Economic studies in dialysis. An essential tool for optimization of resources]. PMID- 17725444 TI - [Interference RNA: A curiosity that merits a Nobel price or a future therapeutic tool]. PMID- 17725445 TI - [Immunosuppressive therapy of primary focal sclerosing glomerulonephritis in the adult: a systematic review]. PMID- 17725446 TI - [Evidence based chronic hemodialysis (I)]. PMID- 17725447 TI - [Recommendations for diagnosis and treatment of aged hypertensives]. PMID- 17725448 TI - [Dialysis and transplant situation, Spain 2004]. PMID- 17725449 TI - [Prevalence of kidney insufficiency in primary care population in Spain: EROCAP study]. AB - This cross-sectional, multicenter study investigated the prevalence of chronic kidney disease and associated disorders, in an adult population sample (> 18 years old) attending Primary Care services in Spain. Estimated glomerular filtration rate (Modification Diet in Renal Disease equation) was used for analysis of kidney disease prevalence according to NFK-KDOQI (The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) stages. Data were collected on serum creatinine, other laboratory parameters blood pressure, and medical history of cardiovascular risk factors or disease (hypertension, dislypidemia, diabetes, congestive heart failure, coronary artery disease, stroke or peripheral arteriopathy) in 7,202 patients attending Primary Care Centers. 47.3% were males, mean age 60,6 +/- 14,3 years, BMI 28.2 +/- 5.3, with 27,6% overweight (27-30 kg/m2) and 32,1% obese (BMI>or=30 kg/m2), The prevalence of cardiovascular risks factors were: absence in 17.3%, one factor 26.9% two 31.2%, and 23.6% presented three or more The frequency of CV risk factors was: hypertension (66.7%), dyslipidemia (48%) and diabetes (31.5%). Congestive heart failure, coronary artery disease, stroke or peripheral vascular disease frequency was lower than 10% The prevalence of eGFR < 60 ml/min x 1.73 m2 was: stage 3 (30 59 ml/min/1.73 m2) 19.7%; stage 4 (15-29 ml/min/1.73 m2) 1.2%; stage 5 no dialysis (GFR < 15 ml/min) 0.4%. This prevalence increased with age in both sexes and 33,7% of patients attending Primary Care services over 70 years presented a eGFR < 60 ml/min. Of the total patients with eGFR < 60 ml/min 37.3% had normal serum creatinine levels. This study documents the substantial prevalence of significantly abnormal renal function among patients at Primary Care level. Early identification and appropriate nephrological management of these patients with renal disease is an important opportunity for an adequate prescription of drugs that interfere with renal function, to delay the progression of renal disease and modify CV risk factors. PMID- 17725450 TI - [The Cockcroft-Gault equation is better than MDRD equation to estimate the glomerular filtration rate in patients with advanced chronic renal failure]. AB - ABSTRACT The aim of this study was to compare the accuracy of three kidney function estimating equations: classic Cockcroft-Gault (classic CG), corrected Cockcroft-Gault (corrected CG) and simplified Modification of Diet in Renal Disease (MDRD), in patients with advanced chronic renal failure. The study was made in 84 nondialyzed patients with chronic renal disease in stage 4 or 5. The glomerular filtration rate was measured on a 24-hour urine collection as the arithmetic mean of the urea and creatinine clearances (CUrCr). In each patient, the difference between each estimating equation and the measured glomerular filtration rate was calculated. The absolute difference expressed as a percentage of the measured glomerular filtration rate indicates the intermethod variability. In the total group the glomerular filtration rate measured as the CUrCr was de 13,5+/-5,1 ml/min/1.73 m(2); and the results of the estimating equations were: classic CG 14,2+/-5 (p<0,05); corrected CG 12+/-4,2 (p<0,01) and MDRD : 12,1+/ 4,8 ml/min/1.73 m(2) (p<0,01). The variability of the estimating equations was 15,2+/-12,2%, 17,1+/-13,4 % and 19,3+/-13,3% (p<0,05), for classic CG, corrected CG and MDRD respectively. The percent of estimates falling within 30% above o below the measured glomerular filtration rate was 90% for CG classic, 87% for corrected CG and 79% for MDRD. The intraclass correlation coefficients respect to CUrCr were 0,86 for classic CG, 0,81 for corrected CG and 0,77 for MDRD. The MDRD variability, but not classic CG variability or corrected CG variability, showed a positive correlation with the glomerular filtration rate (r=0,25, p<0,05). In patients with chronic renal disease in stage 5, the variability of the different estimating equations was similar. We conclude that in our population with advanced chronic renal failure the classic CG equation is more accurate than the MDRD equation. Corrected CG equation has not any advantage respect to classic CG equation. PMID- 17725451 TI - [Therapeutic guidelines fulfillment in clinical practice in patients with chronic kidney disease (CKD)]. AB - OBJECTIVE: The present study was designed to determine the degree of fulfillment of the therapeutic objectives recommended in the clinical guidelines in patients with chronic kidney disease (CKD) in a nephrology outpatient clinic and the treatment that the patients were receiving to control these objectives. METHODS: A descriptive, cross-sectional study was performed in unselected patients with CKD (stages 1-5) who attended the nephrology outpatient clinic of the Hospital General Universitario Gregorio Maranon for follow up between 1st January and 1st April 2006. RESULTS: Data from 600 patients with a mean age of 62.8 years (56.5% male) were collected. The distribution of patients according to the stage (S) of CKD was as follows: S1: 11.5%, S2: 18%, S3: 36.7%, S4: 27.5% and S5: 6.3%. The target blood pressure (BP) < 130/80 mmHg was reached in 35.5%. The target diastolic blood pressure was controlled in 70%. However, systolic blood pressure increasing significantly with age and the degree of renal failure was controlled only in 42%. Total cholesterol was or=50 mg/l in 64.1% of patients. Triglyceride level was related to renal function (p=0.04). Most of the patients (94%) had hemoglobin (Hb) levels >or=11 g/dl, because of a significant increase in the percentage of patients treated with erythropoiesis-stimulating agents as the degree of renal function is reduced. Target levels of calcium-phosphorus (CaXP) product (<55 mg2/dl 2) were maintained in all the stages at the expense of decreased Ca and increased P in relation to the decrease in glomerular filtrate (p=0.001). Target Ca (8.4-9.5 mg/dl) was reached in 85% of cases (2% of patients in S3, 37% of patients in S4 and 54% in S5 were receiving calcitriol). Phosphorus levels were adequate in 80% of patients, but target levels of parathyroid hormone (PTH) were maintained only in 28.6% of patients in S3 (35-70 pg/ml), 14% of patients in S4 (70-110 pg/ml) and 28% in S-5 (115-300 pg/ml). CONCLUSIONS: Anemia is the best controlled factor of all the factors related to renal function. The degree of control of blood pressure (BP) has improved in recent years. However, it is still poor, particularly the control of systolic blood pressure getting worse with renal failure and age. It is difficult to reach the target PTH, despite adequate levels of Ca and P. Cholesterol levels, unlike triglyceride levels, do not depend on renal function and require an increase in the use and/or doses of cholesterol lowering drugs. PMID- 17725452 TI - [Differences in the synthesis pattern of vasoactive factors in gestational hypertension and preeclampsia]. AB - BACKGROUND AND OBJECTIVE: The gestational hypertension -HG- and preeclampsia -P- are hypertensive diseases whose pathogenic mechanism has not been determined yet. The aim of this work is to define some patterns of vasoactive factors release that allow to explain the origin of the differences between both entities. DESIGN: Prospective case-control study. MATERIAL AND METHODS: Two groups of target patients were consecutively selected, GH (n=21) and P patients (n=21). Every patient was matched with a pregnant of similar age and week of pregnancy. Two control groups were obtained, one respect to the GH and another one respect to the P group. A biochemistry, blood cell count, coagulation and quantification of vasoactive factors endothelin, nitrites and GMPc were performed in every woman. Results of GH and P groups were compared with their respective control group with the paired Student's t Test. RESULTS: Both systolic and diastolic arterial pressures were higher in hypertensive pregnants (GH and P) than in their respective controls. Moreover, blood endothelin and GMPc were higher in GH and P. GH pregnants showed decreased norepinephrine and increased epinephrine urinary excretion , as well as an increased plasma nitrites concentration than control group. P patients did not show statistically significant differences in catecholamines urinary excretion nor in plasma nitrites concentration respect their control group. CONCLUSION: There are relevant differences in the synthesis patterns of vasoactive factors between gestational hypertension and preeclampsia. These differences could account for a decreased tissue perfusion in preeclampsia and could also contribute to the genesis of the renal dysfunction of this entity. PMID- 17725453 TI - [Integral management of vascular access by nephrologist. Three years work outcome]. AB - Delay in perform the arteriovenous fistula (AVF) to begin haemodialysis is a major problem in the renal units in our country. Two nephrologists initiated, to solve this problem in its own hospital, to perform AVF from December 2001 to December 31st, 2004. Results were compared to surgical service which performed AVF until December 2001. Reduction in surgical waiting time to perform AVF and percent of patients without AVF at time of initiate haemodialysis treatment are the main results in nephrologists group. No technical differences are found between both groups. These differences come from integral management of AVF, with own and programmed surgical theatre, managed in the office, individualized the patients requirements, and a major surgical flux managed by nephrologists. We conclude that hospitals with a program similar to us with integral approach of AVF and vascular access coordinator, the vascular access could be managed in an efficacy way. PMID- 17725454 TI - [Resistance index to epoetin alpha and to darbepoetin-alpha in chronic hemodialysis patients: a cohort study]. AB - The effectiveness of the erythropoietic response can be evaluated using the resistance index (RI) to erythropoietic agents (EA) that measures the relationship between the dose administered and the hemoglobin levels attained. In a hemodialysis population, the RI is associated with several clinical and biochemical parameters, such as albumin levels, C-reactive protein (CRP), body mass index (BMI) and Kt/V. This index therefore reflects an important group of parameters that indicate comorbidities and measures the effectiveness of the treatment received. A substantial proportion of chronic hemodialysis patients show a relative resistance to human recombinant erythropoietin (rHuEPO) and require high doses to reach hemoglobin levels above 11 g/dl. Darbepoetin alpha is a new erythropoietic agent with a longer half-life than rHuEPO and greater biological activity in vivo. Furthermore, it remains at clinically effective plasma levels for much longer than rHuEPO. This study evaluated the effect on RI of switching from epoetin alpha to darbepoetin alpha in hemodialysis patients requiring i.v. rHuEPO at either high ( >10,000 UI/w) or low ( <4,000 UI/w) doses, compared to a control group receiving epoetin alpha. Unlike the control group, both groups of patients who switched to darbepoetin alpha showed a reduction in RI and a progressive reduction in the dose required of darbepoetin alpha with respect to the equivalent dose at treatment conversion. In the group requiring high doses, darbepoetin alpha RI (DRI) at week 24 was a significant 23.9% lower than epoetin alpha RI (ERI) at conversion (week 0) (p <0.01). In the group requiring low doses, DRI at week 24 was 13.4% lower than the ERI at conversion (p = NS). In both control groups, ERI at week 24 was higher than ERI at week 0. All groups showed stable hemoglobin levels across the study, with mean levels between 11.5 and 13.3 g/dl. CRP at week 24 was significantly related to albumin levels (p <0.001). In conclusion, switching hemodialysis patients from epoetin alpha to darbepoetin alpha was associated with a significant improvement in RI in the group of patients with high doses of EA, which we consider to be an important indicator of the effectiveness and quality of the treatment administered. PMID- 17725456 TI - [Economic study of dialysis using the cost-per-procedure method according to clinical protocols]. AB - Studies analyzing the economic cost of dialysis therapy have raised a considerable interest in the nephrologic community, both inside and outside our country. The objective of the present study was to approach this question from a different point of view, by applying the cost-per-procedure method, according to clinical protocol, to all the routine clinical procedures in our dialysis unit (both Hemodialysis and Peritoneal Dialysis). We analyzed 68 routine protocols (42 for Hemodialysis and 26 for peritoneal Dialysis), carrying out a pormenorized study of all the components of the economic cost of each procedure (personnel, laboratory, surgical and sanitary material, drugs and other concepts). We calculated the final cost of all these procedures after individualizing the different components of the economic spends, with the informatic support of the management department of our center, and in coordination with the data bases of the Pharmacy and General Supplies units. Although the initial implementation of this method is tedious, it subsequently allows to analyze the global cost of therapy in the Unit, as also the cost of certain subsets, or even particular patients, in a simple and flexible way. Moreover, the system is easy to update, as clinical protocols undergo changes or the economic cost of individual components vary. Finally, this method is a useful tool at the time of comparing the cost of clinical procedures in different centres, according to their varying clinical protocols, economic spends and clinical results. PMID- 17725455 TI - [The microbial pattern of the catheter exit-site infection in peritoneal dialysis: A non-diphtheria Corynebacteria emergence?]. AB - BACKGROUND: A prospective cohort study was undertaken to compare the rates of the infecting microorganisms of the peritoneal catheter exit-site in three periods of the prophylactic protocol of a peritoneal dialysis program. All patients treated for more than one month on Peritoneal Dialysis were included: Fourty-eight in Period 1 (P1), 48 in Period 2 (P2), and 54 in Period 3 (P3). Each period was of 3 years. METHODS: Infection prophylaxis protocol: P1: hydrogen peroxide or povidone iodine and non-occlusive dressing; P2: sterile water (boiled water) instead of antiseptic agents, semi-permeable dressing for taking showers, and nasal mupirocine prophylaxis for Staphylococcus aureus carriers; P3: equal to P2, plus local application of antibiotics in equivocal exit-site for infection and argentic nitrate in granulation tissue. MAIN OUTCOME MEASURE: The rates of catheter infection and microorganisms causing infection were analysed by means of the Poisson regression method. Chi-square and ANOVA when appropriate. RESULTS: The proportion of catheters implanted by nephrologist or surgeon (p<0.01) and modality treatment by CAPD or CCPD (p<0.0001) were significantly different in the three periods, while the Staph. Aureus carrieres was in the limit of significance (p=0.048). Throughout the three periods, a significantly decreasing rate of total (P=0.0035) and acute infections (P<0.001), Staph. aureus (P=0.003) and peritonitis (P=0.0025) were found. The Pseudomonas aer. (P=0.006) and Gram negative Bacteria (P=0.023) decreased significantly in P2. The multiple factor analysis included eight factors: sex, age group, ESRD, DM, catheter implantation (nephrologist, surgeon), modality treatment (CAPD, CCPD), manufacturer and prophylaxis period as possible predictors of the catheter infections, the specific microorganisms and the peritonitis. That analysis revealed the prophylaxis period as the main predictive factor of the improvements found (p<0.02,- p<0.001). In contrast, the Corynebacteria spp. increased significantly (P=0.008) throughout the three periods. One half of the Corynebacteria in each period could be considered colonisers. The other half caused true infections, but not one of those episodes required catheter intervention. The non-diphtheria Corynebacteria increase was found related with the continuous cycling Peritoneal Dialysis treatment in multiple factor analysis (p=0.0023) and in the proportion analysis (P=0.039, c2). CONCLUSION: The progressive protocol applied obtained good results, without the continued use of local antiseptics or antibiotics at the exit-site. However, the non-diphtheria Corynebacteria sp. infection increment favours the consideration of an antiseptic agent for the exit-site care. PMID- 17725457 TI - [Hemoperfusion in the treatment of acute valproic acid intoxication]. AB - Valproic acid is increasingly used in the treatment of epilepsy, and also prescribed for bipolar affective disorders, schizoaffective disorders, schizophrenia and migraine prophylaxis. Valproic acid intoxication with suicide attempt is a relatively common clinical problem that can result in coma, respiratory depression, pancytopenia, hemodynamic instability and death. The drug's relatively low molecular weight, small volume of distribution and saturable protein-binding render it potentially amenable to exracorporeal removal (hemodialysis, hemoperfusion or hemofiltration ), but published experience is scarce. We describe a case report involving valproic acid intoxication with ingestion of ethanol, who was successfully treated with charcoal hemoperfusion. With this treatment the half-life of valproic acid was reduced with rapid lowering of valproic acid levels and clinical improvement. Based on our experience in this patient and a review of previously reported cases, charcoal hemoperfusion should be considered for serious valproic acid intoxication because free as well as bound drug fractions are eliminated via this technique. PMID- 17725458 TI - [Renal infarction and kidney rupture: complication of a massive cocaine intoxication in an intestinal carrier]. AB - Major complications derived from the use of cocaine have been described, alter nasal or intravenous administration of the drug. These complications are related to vascular spasm and secondary organ damage. We present the case of an intestinal cocaine packer--in slang, "mule"--, who suffered massive absorption of the drug, resulting n bowel, liver and renal ischemia. This situation, previously undescribe in the literature, ended in kidney rupture. An attempt of embolization, was unsatisfactory, and nephrectomy was finally required. The patient recovered uneventfully, with progressive renal functional improvement. This case, albeit quite exceptional, is illustrative of several of the renal actions of cocaine, and reveals the effects of absorption of cocaine at the intestinal level. PMID- 17725460 TI - [Orthotopic renal transplant: our experience]. PMID- 17725459 TI - [Posttransplant regression of uremic tumoral calcinosis]. AB - Uremic tumoral calcinosis is the massive calcium-phosphate deposits in periarticular tissues, usually around large joints. It has been described between 1-7% hemodialysis patients and although its etiopathogenesis is unknown, it is associated to severe hyperparathyroidism, elevation of the serum calcium phosphorus product or hiperphosphataemia. We describe the case of tumoral calcinosis in the shoulder due to hiperphosphataemia and elevated calcium phosphorus product, treated with low calcium intensive dialysis and fast relapse that disappears after renal transplantation. PMID- 17725461 TI - [Interdisciplinary collaboration in cystinosis diagnosis and monitoring therapy]. PMID- 17725462 TI - [Metformin-associated lactic acidosis and acute renal failure secondary to cardiac catheterism]. PMID- 17725463 TI - [Low blood pressure in hemodialysis]. PMID- 17725464 TI - [Symptomatic hypokalemia associated with Cacchi-Ricci disease]. PMID- 17725465 TI - [Late-onset cytomegalovirus disease following renal transplantation: a report of two cases]. PMID- 17725466 TI - [C-reactive protein, acute or intermediate phase reactant in peritoneal dialysis patients with peritonitis?]. PMID- 17725467 TI - [Rhabdomyolysis due to hypothermia in immigrant illegal patient who arrives in small boat]. PMID- 17725468 TI - [Automatic implantable cardioverter defibrillator in hemodialysis patients]. PMID- 17725469 TI - [Anaphylactoid reaction in hemodyalisis: converting enzyme inhibitors interaction with no PAN 69 membrane]. PMID- 17725470 TI - Fostering clinician-led research. PMID- 17725471 TI - A novel weight-bearing strengthening program during rehabilitation of older people is feasible and improves standing up more than a non-weight-bearing strengthening program: a randomised trial. AB - QUESTION: What is the feasibility and effectiveness of a novel weight-bearing strengthening program compared with that of a traditional non-weight-bearing strengthening program for older inpatients undergoing rehabilitation? DESIGN: Randomised, controlled trial with concealed allocation, assessor blinding, and intention-to-treat analysis. PARTICIPANTS: Eighty-eight inpatients (11% loss to follow-up) aged on average 82 years old from three rehabilitation units with no contraindications to exercise. INTERVENTION: Both the weight-bearing and non weight-bearing strengthening programs were supervised by physiotherapists and were of similar intensities (10 to 15 RM) for two weeks. OUTCOME MEASURES: The primary outcomes were standing up performance measured as minimum chair height, and strength measured as maximum isometric knee extensor force of both legs. The secondary outcomes were other mobility measures such as standing-up rate, walking, standing and overall mobility, and other strength measures such as maximum isometric hip extensor, hip abductor, and knee flexor force of both legs. RESULTS: After the two-week intervention, the weight-bearing strengthening group had decreased their minimum chair height by 5.3 cm (95% CI 0.7 to 9.8) and increased their hip extensor strength on the weaker leg by 9 N (95% CI 1 to 17) more than the non-weight-bearing strengthening group. There were no clinically worthwhile or statistically-significant differences between the groups for any other measures. CONCLUSION: This novel weight-bearing strengthening program was feasible and safe in an inpatient rehabilitation setting and had some additional benefits over a traditional non-weight-bearing strengthening program. PMID- 17725472 TI - In chronic low back pain, low level laser therapy combined with exercise is more beneficial than exercise alone in the long term: a randomised trial. AB - QUESTION: Is low level laser therapy an effective adjuvant intervention for chronic low back pain? DESIGN: Randomised trial with concealed allocation, blinded assessors and intention-to-treat analysis. PARTICIPANTS: Sixty-one patients who had low back pain for at least 12 weeks. INTERVENTION: One group received laser therapy alone, one received laser therapy and exercise, and the third group received placebo laser therapy and exercise. Laser therapy was performed twice a week for 6 weeks. OUTCOME MEASURES: Outcomes were pain severity measured using a 10-cm visual analogue scale, lumbar range of motion measured by the Schober Test and maximum active flexion, extension and lateral flexion, and disability measured with the Oswestry Disability Index on admission to the study, after 6 weeks of intervention, and after another 6 weeks of no intervention. RESULTS: There was no greater effect of laser therapy compared with exercise for any outcome, at either 6 or 12 weeks. There was also no greater effect of laser therapy plus exercise compared with exercise for any outcome at 6 weeks. However, in the laser therapy plus exercise group pain had reduced by 1.8 cm (95% CI 0.1 to 3.3, p = 0.03), lumbar range of movement increased by 0.9 cm (95% CI 0.2 to 1.8, p < 0.01) on the Schober Test and by 15 deg (95% CI 5 to 25, p < 0.01) of active flexion, and disability reduced by 9.4 points (95% CI 2.7 to 16.0, p = 0.03) more than in the exercise group at 12 weeks. CONCLUSION: In chronic low back pain low level laser therapy combined with exercise is more beneficial than exercise alone in the long term. PMID- 17725473 TI - A recruitment manoeuvre performed after endotracheal suction does not increase dynamic compliance in ventilated paediatric patients: a randomised controlled trial. AB - QUESTION: Does a recruitment manoeuvre after suctioning have any immediate or short-term effect on ventilation and gas exchange in mechanically-ventilated paediatric patients? DESIGN: Randomised controlled trial with concealed allocation, assessor blinding, and intention-to-treat analysis. PARTICIPANTS: Forty-eight paediatric patients with heterogeneous lung pathology. Fourteen patients were subsequently excluded from analysis due to large leaks around the endotracheal tube. INTERVENTION: The experimental group received a single standardised suctioning procedure followed five minutes later by a standardised recruitment manoeuvre. The control group received only the single suctioning procedure. OUTCOME MEASURES: Measurements of ventilation (dynamic lung compliance, expiratory airway resistance, mechanical and spontaneous expired tidal volume, respiratory rate) and gas exchange (transcutaneous oxygen saturation) were recorded, on three occasions before and on two occasions after the recruitment manoeuvre, using a respiratory profile monitor. RESULTS: There was no difference between the experimental and the control group in dynamic compliance, expired airway resistance, or oxygen saturation either immediately after the recruitment manoeuvre, or after 25 minutes. The experimental group decreased mechanical expired tidal volume by 0.3 ml/kg (95% CI 0.1 to 0.6), increased spontaneous expired tidal volume by 0.3 ml/kg (95% CI 0.0 to 0.6), and increased total respiratory rate by 3 bpm (95% CI 1 to 4) immediately after the recruitment manoeuvre compared with the control group, but these differences disappeared after 25 minutes. CONCLUSION: There is insufficient evidence to support performing recruitment manoeuvres after suctioning infants and children. PMID- 17725474 TI - In private practice, informed consent is interpreted as providing explanations rather than offering choices: a qualitative study. AB - QUESTION: How do physiotherapists working in private practice understand and interpret the meaning and significance of informed consent in everyday clinical practice? DESIGN: Qualitative study using semi-structured interviews. PARTICIPANTS: Seventeen physiotherapists purposefully recruited from metropolitan private practices where treatment was on a one-on-one basis. RESULTS: Therapists defined informed consent as an implicit component of their routine clinical explanations, rather than a process of providing explicit patient choices. Therapists' primary concern was to provide information that led to a (therapist determined) beneficial therapeutic outcome, rather than to enhance autonomous patient choice. Explicit patient choice and explicit informed consent were defined as important only if patients requested information or therapists recognised risks associated with the treatment. CONCLUSION: Physiotherapists defined informed consent within a context of achieving therapeutic outcomes rather than a context of respect for patient autonomy and autonomous choice. Physiotherapy practice guidelines developed to ensure compliance with ethical and legal obligations may therefore be followed only if they fit with therapists' understanding and interpretation of a desired therapeutic outcome. PMID- 17725475 TI - Position affects distribution of ventilation in the lungs of older people: an experimental study. AB - QUESTION: What is the effect of sitting and side-lying on the distribution of ventilation during tidal breathing in healthy older people? DESIGN: Randomised, within-participant, experimental study. PARTICIPANTS: Ten healthy people more than 65 years old. INTERVENTION: Tidal breathing during sitting and right side lying. OUTCOME MEASURES: Distribution of ventilation as a percentage of total counts using Technetium-99m Technegas lung ventilation imaging. RESULTS: In sitting, the ratio of the distribution of ventilation to apical: middle: basal regions was 1: 3.5: 3.3 in the right lung, and 1: 2.9: 2.3 in the left lung. In right side-lying, 32% (95% CI 22 to 43) more ventilation was distributed to the right lung than to the left lung. The ratio of the distribution of ventilation to apical: middle: basal regions was 1: 2.8: 2.2 in the right lung, and 1: 2.4: 1.9 in the left lung. CONCLUSIONS: In both sitting and right side-lying, ventilation was distributed more to the middle than to the basal region, which may be related to age-associated changes in the respiratory system. PMID- 17725476 TI - Healthy adults can more easily elevate the pelvic floor in standing than in crook lying: an experimental study. AB - QUESTIONS: Are there any differences in the displacement and endurance of an elevating voluntary pelvic floor muscle contraction in standing and in crook lying? Are there any differences in these variables between males and females in either test position? DESIGN: An experimental study. PARTICIPANTS: Forty-five nulliparous female and 20 male participants aged 23 years (SD 3) with no symptoms of urinary incontinence or low back pain. INTERVENTION: Voluntary pelvic floor muscle contraction was measured in both standing and crook-lying. OUTCOME MEASURES: Transabdominal ultrasound was used to measure the displacement (mm) and endurance (s) of pelvic floor elevation. RESULTS: Displacement was greater in standing than in crook-lying (mean difference 2.6 mm, 95% CI 1.5 to 3.7). There was no difference between males and females (mean difference 1.3 mm, 95% CI 0.5 to 3.2). Similarly, endurance of pelvic floor elevation was longer in standing than in crook-lying (mean difference 17.3 s, 95% CI 12.2 to 22.4). Again there was no difference between males and females (mean difference 0.5 s, 95% CI 9.3 to 8.3). CONCLUSION: Standing was found to be a more effective position for achieving and sustaining an elevation of the pelvic floor compared to crook lying, regardless of sex, and this should be taken into account when assessing and training pelvic floor muscle contraction. PMID- 17725478 TI - Bioengineering assessment of acupuncture, part 5: cerebral near-infrared spectroscopy. AB - The assessment of cortical activation in the brain due to acupuncture is crucial. Thus far functional assessment of cortical responses to certain external stimuli (for examples, manual needle, optical, electrical) are very few due to the lack of suitable techniques to monitor changes of brain activities. Near-infrared spectroscopy has been found to be suitable for functional studies during acupuncture. By this neuromonitoring method, hemodynamic changes coupled to cortical activity can be monitored. Near-infrared spectroscopy is used to measure regional changes in oxyhemoglobin, deoxyhemoglobin, and cytochrome aa3 noninvasively and continuously. The studies in this fifth part of a review article, which have been carried out mainly by the research group of Biomedical Engineering in Anesthesia and Intensive Care Medicine at the Medical University of Graz, demonstrate that near-infrared spectroscopy is a suitable technique for the assessment of cortical changes in response to varying forms of acupuncture. The method is likely to play an important role in providing new insights into the effects of acupuncture on brain function. PMID- 17725477 TI - Loss of proprioception or motor control is not related to functional ankle instability: an observational study. AB - QUESTIONS: Is loss of proprioception or loss of motor control related to functional ankle instability? Are proprioception and motor control related? Is there any difference in proprioception or motor control between ankles with different severity of functional ankle instability? DESIGN: Cross-sectional, observational study. PARTICIPANTS: Twenty people aged between 18 and 40 years with functional ankle instability associated with a history of ankle sprain more than one month prior. Twenty age-matched controls with no functional ankle instability or history of ankle sprain. OUTCOME MEASURES: Functional ankle instability was classified using the Cumberland Ankle Instability Tool, proprioception at the ankle was measured as movement detection at three velocities, and motor control was measured using the Landing Test and the Hopping Test. RESULTS: There was little if any relation between proprioception (r = 0.14 to 0.03, 95% CI 0.40 to 0.25) or motor control (r = 0.08 to 0.07, 95% CI 0.35 to 0.20) and functional ankle instability. There was also little if any relation between proprioception and motor control except for a low correlation between movement detection at 0.1 deg/s and the Landing Test (r = 0.35, 95% CI 0.09 to 0.58). Furthermore, there was no difference between the ankles with or without functional ankle instability in proprioception or motor control. CONCLUSION: By greater than one month after ankle sprain, loss of proprioception does not make a major contribution to functional ankle instability. PMID- 17725479 TI - Thermal therapy, part 1: an introduction to thermal therapy. AB - Thermal therapy is widely known and electromagnetic (EM) energy, ultrasonic waves, and other thermal-conduction-based devices have been used as heating sources. In particular, advances in EM technology have paved the way for promising trends in thermotherapeutical applications such as oncology, physiotherapy, urology, cardiology, ophthalmology, and in other areas of medicine as well. This series of articles is generally written for oncologists, cancer researchers, medical students, biomedical researchers, clinicians, and others who have an interest in this topic. This article reviews key processes and developments in thermal therapy with emphasis on two techniques, namely, hyperthermia [including long-term low-temperature hyperthermia (40-41 degrees C for 6-72 hr), moderate-temperature hyperthermia (42-45 degrees C for 15-60 min), and thermal ablation, or high-temperature hyperthermia (> 50 degrees C for > 4-6 min)]. The article will also provide an overview of a wide range of possible mechanisms and biological effects of heat. This information will be discussed in light of what is known about the degree of temperature rise that is expected from various sources of energy. The review concludes with an evaluation of human exposure risk to EM energy or the corresponding heat, trends in equipment development, and future research directions. PMID- 17725480 TI - Thermal therapy, part 2: hyperthermia techniques. AB - Hyperthermia, the procedure of raising the temperature of a part of or the whole body above normal for a defined period of time, is applied alone or as an adjunctive with various established cancer treatment modalities such as radiotherapy and chemotherapy. Clinical hyperthermia falls into three broad categories, namely, (1) localized hyperthermia, (2) regional hyperthermia, and (3) whole-body hyperthermia (WBH). Because of the various problems associated with each type of treatment, different heating techniques have evolved. In this article, background information on the biological rationale and current status of technologies concerning heating equipment for the application of hyperthermia to human cancer treatment are provided. The results of combinations of other modalities such as radiotherapy or chemotherapy with hyperthermia as a new treatment strategy are summarized. The article concludes with a discussion of challenges and opportunities for the future. PMID- 17725482 TI - Molecular signaling in bone regeneration. AB - Regeneration is the ability of cells to restore lost or damaged tissues and organs in adults by pathways that mimic developmental processes. Although many of the molecular mechanisms that control cellular differentiation and growth during embryogenesis recur during fracture healing, these processes take place in a postnatal environment that is unique and distinct from those that exist during embryogenesis. Bone tissue has a remarkable capacity of regeneration without scarring. This article highlights central biological and molecular processes that are crucial in embryonic bone development. Several animal bone regeneration models are described. The patterns of gene expression during the regeneration process in the different models are reviewed. Exploring the similarities and the differences in the molecular processes in different models will contribute to the understanding of their potential in the processes of bone regeneration and tissue engineering. PMID- 17725483 TI - Insights on the functional role of chromatin remodelers in osteogenic cells. AB - Control of eukaryotic gene expression requires interaction between sequence specific transcription factors and their regulatory elements on the particular promoter. The dynamic alteration of chromatin structure regulates the accessibility of these elements in the genome and therefore contributes to the control of transcriptional activity. Here we discuss chromatin remodelling in the context of osteoblast lineage regulation. This review specifically highlights the role of the protein chromatin-related mesenchymal modulator (CReMM/CHD9), a recently identified chromatin remodeler, in osteogenic cell differentiation. PMID- 17725484 TI - Vitamin D modulation of the activity of estrogenic compounds in bone cells in vitro and in vivo. AB - Vitamin D analogs modulate different organs, including modulation of energy metabolism, through the induction of creatine kinase (CK) activity. Skeletal organs from vitamin D-depleted rats showed lower constituent CK than those from vitamin D-replete rats. Moreover, estradiol-17beta (E2) or dihydrotestosterone (DHT), which increased CK in organs from intact female or male rats, respectively, stimulated much less CK in vitamin D-depleted rats. Treatment of intact female rats with noncalcemic vitamin D analogs significantly upregulated E2- and DHT-induced CKresponse. These analogs upregulated the CK response to selective estrogen receptor modulators (SERMs) in organs from intact or ovariectomized (Ovx) female rats but abolished SERMs' inhibitory effect on E2 induced CK. These analogs significantly increased estradiol receptor alpha (ERalpha) protein in skeletal organs as well as histomorphological and biochemical changes due to this treatment followed by E2 or DHT. The analogs alone markedly altered the growth plate and the trabeculae and increased trabecular bone volume (%TB V) and trabecular width. The addition of E2 or DHT to this treatment restored all parameters as well as increased %TBV and cell proliferation. Treatment of Ovx female rats with JK 1624 F2-2 (JKF) decreased growth-plate width and increased %TB V, whereas QW1624 F2-2 (QW) restored growth plate width and %TB V. Treatment of E2 with JKF restored %TBV and growth-plate width, whereas E2 with QW restored all parameters, including cortical width. There was also upregulation of the response of CK to E2 in both combined treatments. Our human-derived osteoblast (hObs)-like cell cultures respond to estrogenic compounds, and pretreating them with JKF upregulated the CK response to E2, raloxifene (Ral), and some phytoestrogens. ERalpha and ERbeta proteins, as well as mRNA, were modulated by CB 1093 (CB) and JKF. JKF increased specific nuclear E2 binding in female hObs but inhibited specific membranal E2 binding. hObs express 25 hydroxyvitamin D3-1alpha hydroxylase (1-OHase)-mRNA and its biological activity, which are both modulated by parathyroid hormone (PTH) and estrogenic compounds. Our results demonstrate mutual interaction between vitamin D and estrogenic compounds. We therefore conclude that combined treatment with less-calcemic analogs of vitamin D and estrogenic compounds might be superior for treatment of bone damage caused by ovariectomy in female rats, with possible application for postmenopausal osteoporosis. PMID- 17725485 TI - Responsiveness of osteoblastic and osteolytic bone metastases to vitamin D analogs. AB - Bone is the primary site of metastases in advanced androgen-independent prostate cancer. These metastases are primarily bone-forming, although the presence of osteolytic response has also been reported. Bone-homing therapy is a strategy based on the popular seed-and-soil relationship between the epithelial malignant cells and the bone stroma. Calcitriol (1,25-dihydroxyvitamin D3) and its synthetic analogs (deltanoids) are drugs that have a direct effect on both the skeleton and the invading metastatic cells and, therefore, are considered useful in the treatment of advanced prostate cancer. In this article, I review the nature of the response induced by the malignant cells in the bone (bone formation or bone resorption) and how it affects the outcome of a vitamin D analog treatment in preclinical models of metastatic bone disease. PMID- 17725486 TI - Heparan sulfate control of proliferation and differentiation in the stem cell niche. AB - Tissue-specific stem cell populations are established in "niches," anatomic locations with precise biochemical and cellular configurations that regulate their release and participation in tissue generation, maintenance, and repair. Niches have evolved to protect and perpetuate the self-renewing, undifferentiated state of the cells within and to regulate the rate of production of committed, tissue-specific progenitors. A niche thus integrates the cell growth, cell adhesion, and cell-cell signals that mediate the balanced response of stem cells to the needs of the organism. One constituent of every niche with the capacity to mediate almost all of the required functions is the glycosaminoglycan sugar heparan sulfate. This sugar is a master regulator of mitogenic and adhesive molecule behavior with the ability to rapidly change its binding affinities on the cell surface. Its properties may be the key to understanding the interplay between stem cells and their niche that creates the dynamic system necessary for sustaining tissues. As such, it has great promise for the design of tissue specific stem cell therapeutics. PMID- 17725487 TI - Role of DLX regulatory proteins in osteogenesis and chondrogenesis. AB - Bone development is a complex process in which several cell types interact, proliferate, differentiate, and die to give rise to skeletal structures. These processes are highly integrated and require continuous and coordinated regulation by soluble molecular signals and transcription factors to assure harmonious bone development and morphogenesis. In the bone, transcription factors often have multiple functions and control the differentiation of more than one skeletal cellular component. In particular, Distal-less (Dlx) homeobox transcription factors play a central role in regulating the proliferation and differentiation of the three major cell types that constitute bone: chondrocytes, osteoblasts, and osteoclasts. The aim of this review is to summarize what is known about the role of Dlx genes in osteogenesis and to emphasize their role as coordinators at different levels of skeletal development. The elucidation of these unifying roles could improve our understanding not only of bone development but also of adult bone anabolism and catabolism resulting in bone homeostasis and might thus help to further our understanding of the genetic factors responsible for predisposition to multifactorial conditions such as osteoporosis. PMID- 17725488 TI - Histone deacetylase co-repressor complex control of Runx2 and bone formation. AB - A decade has passed since the transcription factor, Runx2, was found to be essential for osteoblast development and chondrocyte hypertrophy. During the last 10 years, our understanding of Runx2's physiological roles and the molecular mechanisms whereby it regulates gene expression to control cell-cycle progression and cellular differentiation has increased exponentially. Runx2 is expressed in osteoblasts, prehypertrophic chondrocytes, mesenchymal cells of the perichondrium, T lymphocytes, endothelial cells, and breast and prostate epithelial cells, with increased expression observed in breast and prostate carcinomas. Although Runx2 and other mammalian Runt domain proteins were originally described as transcriptional activators, they are also transcriptional repressors and thus maintain functional similarities with their Drosophila homolog, Runt. Runx2 binds a consensus DNA sequence but does not possess any enzymatic activities that directly affect chromatin structure. It alters gene expression by recruiting cofactors to gene regulatory elements. Histone deacetylases (HDACs) are among the co-repressors that interact with Runx2. In this review, we summarize data demonstrating that several HDACs and their associated proteins interact with Runx2, regulate its activity, and affect bone formation. HDACs are components of multiprotein complexes that interact with many transcription factors and are subject to regulation by extracellular signals. The elucidation of HDAC complex components that influence Runx2 activity in specific cell types and in response to various extracellular stimuli will increase our understanding of how this crucial transcription factor functions, and how we might be able to control its activity to influence bone formation or reduce bone disease associated with cancer metastasis. PMID- 17725489 TI - Role of bone regeneration and turnover modulators in control of fracture. AB - Although most fractures heal in accordance with a highly regulated and well-known multistep process, 5%-10% of fractures result in delayed union or nonunion, causing morbidity, prolonged hospitalization, and economic cost for the individual and society. Ongoing research has improved our understanding of genes and molecules that are expressed during fracture healing. This knowledge has been translated into preclinical/clinical trials. Unfortunately, the success of most promising agents, and therefore most preclinically/clinically tested factors, is controversial and frequently disappointing. Taking advantage of our knowledge concerning the temporal events contributing to fracture healing, and as a result of our studies, we suggest that the application of several factors in sequence will intervene in different, crucial crossroads, accelerate remodeling, and result in an improved outcome. These factors will encompass stimulated recruitment and proliferation of stem cells to enlarge the progenitor pool, facilitate its differentiation into mature chondrocytes and osteoblasts, and stimulate cartilage resorption and its remodeling into bone by endochondral ossification--a process in which blood vessels, metalloproteinases, and osteoclasts work in concert to remodel immature bone into mature bone. The aim of this article is to highlight events that contribute to and drive the dynamic healing process in order to help clinicians to find successful, novel treatment protocols. PMID- 17725490 TI - Pathophysiology and genetics of metabolic bone disorders characterized by increased bone turnover. AB - Bone is the most important supportive tissue in the human body, and in order to maintain its integrity, it is continuously renewed by a process called "remodeling". Paget's disease of bone (PDB), familial expansile osteolysis (FEO), expansile skeletal hyperphosphatasia (ESH), early-onset Paget's disease of bone (EOPDB), and juvenile Paget's disease (JPD) are all metabolic bone disorders characterized by accelerated bone remodeling. Histological studies have shown that bone-resorbing osteoclasts are the primary disease-causing cells in these disorders. In this review, we provide an overview of the clinical differences between diseases with increased bone turnover. Our main focus is on Paget's disease because this is, by far, the most common form of this type of disease. Molecular genetic studies of these disorders have revealed key players in bone remodeling and have provided further insights in signal transduction in osteoclasts. Moreover, a syndromal form of PDB has been characterized in which PDB is associated with inclusion body myopathy and frontotemporal dementia, pointing toward similar biological pathways in osteoclasts, muscle, and brain cells. However, several additional genes underlying conditions with increased bone turnover remain to be identified. PMID- 17725491 TI - Signaling mucins: the new kids on the MAPK block. AB - Signaling mucins are an emerging group of cell adhesion receptors that activate mitogen-activated protein kinase (MARK) pathways at the level of RAS/RHO. Recent discoveries on several fronts, including in the model eukaryote budding yeast, have broadened our understanding of this family of signaling molecules. Progress in characterizing three signaling mucins, MUC1, Muc4, and Msb2, points to a surprising degree of functional overlap in the regulation and mechanism-of activation of these molecules. The prevailing new insight is one of receptor activation by proteolytic cleavage that closely mirrors the developmental signaling factor, Notch. The unexpected parallels between signaling mucins and Notch spark new questions about mucin activation and provoke a double take at this fledgling class of signaling adhesion molecule. PMID- 17725492 TI - The phosphoinositide-phospholipase C (PI-PLC) pathway in the mouse oocyte. AB - As highlighted in this review, the phosphoinositide-phospholipase C pathway is strongly implicated in the control of mouse oocyte meiosis. The pathway becomes progressively functional as oocyte growth advances, and it appears to play a role in the G2/M transition when meiosis resumes, at least in the in vitro spontaneous model. Even if the inositol 1,4,5-trisphosphate receptors are present from the beginning, they function and release Ca2+ when the follicular antrum appears. Phospholipase C beta1 (PLC beta 1) is first exclusively localized to the nucleus and then migrates to the cytoplasm when the oocyte is fully grown. During oocyte maturation PLC beta 1 is active in the cytoplasm before it migrates and becomes active in the nucleus just prior to germinal vesicle breakdown. Because a similar circuit is observed for protein kinase C alpha (PKC alpha), PKC beta 1, PKC beta 2, and active mitogen-activated protein kinase, it is tempting to envisage that a feedback loop occurs between these pathways as demonstrated in other cell types. The chronology of these molecular movements into the oocyte reveals the particular and important role of the nucleus phosphoinositide cycle during oocyte meiosis. It appears also that this chronology is crucial and that defects leading to an inappropriate intracellular localization can have dramatic consequences. Such anomalies can prevent the production of competent oocytes and lead to fertility problems. PMID- 17725493 TI - Regulation of RUNX1 transcriptional function by GATA-1. AB - Runt-related transcription factor 1 (RUNX1) and GATA-1 are both transcription factors known to play essential roles in hematopoiesis. Genetic alterations of each are associated with abnormal platelet development, as well as predisposition to leukemia. In addition, in vitro and animal studies indicate that both factors are involved in megakaryopoiesis. We and others have previously shown that RUNX1 and GATA-1 physically interact and cooperate in the activation of megakaryocytic promoters such as alpha IIb integrin and glycoprotein Ibalpha. Moreover, transcriptional cooperation of RUNX1 with GATA-1 is conserved back to Drosophila in which RUNX1 and GATA-1 homologs cooperate in crystal cell development. In this article, we will review the molecular and functional significance of the transcriptional cross talk between RUNX1 and GATA-1. In particular, we will elaborate on recent data which suggest that GATA-1 targets RUNX1 for modification, in particular phosphorylation by cyclin-dependent kinases. Furthermore, targeting of RUNX1 by GATA-1 for phosphorylation may convert RUNX1 from a repressor to an activator. This is a potential mechanism of transcriptional cooperation and may be an essential step in megakaryocytic differentiation. PMID- 17725495 TI - Epigenetic control of tumor suppression. AB - Epigenetic silencing of tumor suppressor genes is a major contributor to neoplastic transformation and is an area of intense research. Identification of genes that undergo cancer-specific CpG island hypermethylation in combination with repressive histone tail modifications (deacetylation and methylation) and correlation of these data with tumor stage, progression, and long-term prognosis are becoming increasingly common. The efforts directed toward elucidating the mechanisms of neoplastic tumor suppression catalyzed the convergence of epigenetics, chromatin remodeling, and pharmacology of epigenome-altering drugs. This review discusses the key findings and current concepts concerning the epigenetic control of tumor suppression and analyzes the role of DNA hypermethylation in conjunction with histone deacetylation and methylation profiles of tumor suppressor genes as it relates to epigenetic loss of function in malignancy. Examples arguing for hierarchic control and interdependent regulation within the cellular tumor suppression networks are also presented. Finally, the necessity of a human epigenome database integrating the continually produced experimental information for use by both researchers and clinicians for prospective translational multidisciplinary studies of tumor suppressor networks is rationalized. PMID- 17725496 TI - Involvement of prelamin A in laminopathies. AB - The precursor protein of the nuclear lamina constituent lamin A is a 74-kDa protein called prelamin A which undergoes subsequent steps of posttranslational modification at its C-terminal CaaX residue. The unexpected finding that accumulation of unprocessable prelamin A is the molecular basis of the most severe laminopathies so far identified, including Hutchinson-Gilford progeria and restrictive dermopathy, has opened new perspectives in the study of the pathogenic mechanisms causing all lamin A/C-linked disorders, as well as new interest in the analysis of molecular mechanisms regulating prelamin A processing. However, complete knowledge of the cellular pathways affected downstream of prelamin A accumulation is still lacking, but it could give new insights both in normal and pathogenic mechanisms regulated by lamins. In this article, we review the involvement of defects of prelamin A processing in the pathogenesis of a group of laminopathies. In particular, we discuss the possibility that mutations leading to accumulation of particular forms of prelamin A result in specific nuclear abnormalities and impairment of nuclear functions leading to cell senescence or altered metabolism. PMID- 17725497 TI - Parameters of quantitative trait loci. AB - Most traits of medical relevance follow quantitative inheritance patterns. The genetic dissection of quantitative traits poses special challenges for geneticists mainly because of low penetrance and gene-gene and gene-environment interactions. Emerging genome resources and technologies are enabling systematic investigation of the genetic architecture of quantitative traits in more efficient ways. This article summarizes the current state of medical quantitative trait locus (QTL) mapping-describing the methods, limitations, and achievements in the detection and characterization of QTLs. PMID- 17725499 TI - Immune-modulatory effects and potential working mechanisms of orally applied nondigestible carbohydrates. AB - Orally applied nondigestible carbohydrates (NDC) have been associated with immune modulating effects and other health benefits. The effects of prebiotic carbohydrates have recently received much attention, but other NDC have been reported to induce immune modulation as well. Many different effects have been shown on parameters of innate and specific immunity, mostly in animal experiments or in vitro. Data from clinical trials are limited, but promising studies have reported beneficial effects on mucosal and systemic immunity in humans. NDC are fermented to various degrees by the intestinal microbiota. Therefore, immune modulatory properties have often been attributed to microbiota-dependent effects, especially in the case of prebiotic NDC. However, some NDC have been reported to bind to specific receptors on cells of the immune system, suggesting microbiota independent, immune-modulatory effects play a role as well. This review aims to provide an overview of the published immune-modulatory effects in vitro and in vivo induced by NDC such as fructans, galactooligosaccharides, beta-glucans, pectins, and resistant starch. In addition, issues related to the underlying mechanisms are discussed: interaction between bacteria, their metabolites and the immune system, as well as direct effects of NDC via lectin receptors. PMID- 17725494 TI - Roles of Smad3 in TGF-beta signaling during carcinogenesis. AB - Signaling of transforming growth factor beta (TGF-beta) is mediated through a heteromeric complex of two types of transmembrane receptors and downstream intracellular proteins known as Smads. Alterations of TGF-beta signaling underlie various forms of human cancer and developmental diseases. Human genetic studies have revealed both point mutations and deletions of Smad2 or Smad4 in several types of cancers. However, the role of Smad3 in tumorigenesis is not clear. Recent data indicate that Smad3 also functions as a tumor suppressor by inhibiting cell proliferation and promoting apoptosis. In addition, Smad3 is essential for TGF-beta-mediated immune suppression, and it plays an important role in regulating transcriptional responses that are favorable to metastasis. Therefore, through regulating different transcriptional responses, Smad3 functions as both a negative and positive regulator of carcinogenesis depending on cell type and clinical stage of the tumor. PMID- 17725500 TI - Novel functions of B cells. AB - T cells clearly help B cells to produce antibodies and acquire memory. Recently, B cells were found to support some T-cell responses through antigen presentation, and perhaps more importantly, through the generation of diverse T cells and lymphoid organogenesis. These new findings show that the development and function of T cells depend on B cells independently of specific antibody production. PMID- 17725501 TI - Spectrum of the early xenograft response: from hyperacute rejection to delayed xenograft injury. AB - Hyperacute xenograft rejection is a well-defined barrier to clinical pig-to-human xenotransplantation, and intense research in this area has identified potential solutions. In contrast, the next phase of xenograft injury, which can occur days to weeks later, has introduced a new series of immunological and nonimmunological barriers with complex mechanisms. This review addresses mechanisms of the immediate and delayed xenograft response with a focus on the relevant components. The key individual elements include carbohydrate antigens and natural antibodies to these epitopes, the role of the complement and coagulation systems, and the inflammatory cellular xenograft response that is predominantly mediated by the innate immune system. The vascular elements are central targets in this process, and the role of the endothelial cell is discussed. Important recent developments in xenotransplantation include the production of genetically modified pigs (deficient in alphaGal transferase and pigs transgenic for complement regulators) and a progressive understanding of xenograft-induced thrombotic microangiopathy, which threatens the long-term survival of transplanted pig organs and tissue. However, a clear standardized classification of the immunopathological mechanisms involved is essential. Further studies into the delayed xenograft response, using primates, are required before the routine use of pig organs for clinical transplantation. PMID- 17725502 TI - Progress toward antibody-induced transplantation tolerance. AB - Transplantation tolerance remains an elusive goal. Despite multiple animal models of tolerance induction using a variety of agents and protocols, it has yet to be achieved in humans with any predictability. In this review, we examine some of the antibodies directed toward T cells that show promise in prolonging graft survival in animal models and in preliminary clinical assessment. Because these antibodies work through multiple pathways, including depletion, downregulation, receptor-ligand blockade, and direct signaling, they have also helped us tease out the various components of long-lived donor-specific tolerance. In particular, we review the role of the thymus in therapies targeted at the peripheral immune system; the importance of the thymus in tolerance induced by anti-CD45RB suggests that central tolerance mechanisms may be more important than previously appreciated. PMID- 17725503 TI - A brief account of an adventurous journey in the neurosciences. A tribute to the contributions of Dr. Kresimir Krnjevic. PMID- 17725504 TI - The need for animal models in small-vessel brain disease. AB - An argument is made that small-vessel stroke, which usually results in lacunar infarction, is a serious medical problem. Therefore, it is surprising that only a few animal models exist that mimic small-vessel stroke and that these models have not been used for a systematic investigation of the genesis of lacunar infarctions. We make a case that the modified pial vessel class II disruption model mimics certain important aspects of lacunar infarctions, namely cavitation caused specifically by ischemia of smaller vessels. We found evidence that upregulation of inflammatory properties within a few days of inducing lesions prevents repopulation of the lesion with reactive astrocytes. We propose that this is the key mechanism by which cavitation occurs weeks later. We also found that treatment with minocycline after induction of lesions but before cavitation prevented the formation of the fluid-filled cavity. Rather than being walled off, the lesion apparently became part of the brain parenchyma and consisted of reactive astrocytes. We conclude that this new model can be used to investigate the mechanism of lacune formation and its prevention. PMID- 17725505 TI - Role of giant depolarizing potentials in shaping synaptic currents in the developing hippocampus. AB - Early in development, network activity in the hippocampus is characterized by giant depolarizing potentials (GDPs). These potentials consist of recurrent membrane depolarizations with superimposed fast action potentials separated by quiescent intervals. They are generated by the interplay of glutamate and gamma aminobutyric acid (GABA) that, in the immediate postnatal period, is depolarizing and excitatory. Here, we review some recent data concerning the functional role of GDPs in shaping synaptic currents at low-probability mossy-fiber (MF)-CA3 synapses. A pairing procedure was used to correlate GDPs-associated calcium increase in the postsynaptic cell with stimulation of afferent inputs. The pairing protocol caused the appearance of synaptic responses or persistently enhanced the number of successes in "presynaptically" silent or low-probability synapses, respectively. In double-pulses experiments, this effect was associated with a significant reduction in the paired-pulse ratio and a significant increase in the inverse squared value of the coefficient of variation of response amplitude, suggesting that long-term potentiation (LTP) expression was due to the increased probability of transmitter released. In the absence of pairing, no significant changes in synaptic efficacy could be detected. When the interval between GDPs and MF stimulation was increased, the potentiating effect progressively declined and reached the control level in less than 4 s. Mossy fiber responses were identified on the basis of their paired-pulse facilitation, short-term frequency facilitation, and sensitivity to the group III metabotropic glutamate receptor (mGluR) agonist, 2-amino-4-phosphonobutyric acid (L-AP4). Using these criteria, we found that MFs release mainly GAB A onto CA3 pyramidal cells or GABAergic interneurons. In line with their GABAergic nature, MF responses were blocked by the GABAA receptor antagonists bicuculline or gabazine and were potentiated by NO-711, a blocker of the GABA transporter GAT-1, and by flurazepam, an allosteric modulator of GABAA receptors. In addition, chemical stimulation of granule cell dendrites with glutamate in the presence of 6,7 dinitroquinoxaline-2,3-dione (DNQX) induced into target neurons barrages of L-AP4 sensitive GABAA-mediated postsynaptic currents, further supporting the GABAergic phenotype of granule cells. As in MF, pairing GDPs with Schaffer collateral stimulation induced a persistent potentiation of spontaneous and evoked alpha amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-mediated responses at poorly developed CA3-CA1 synapses. This effect was mediated by an increase in calcium in the postsynaptic cell via voltage-dependent calcium channels activated by the depolarizing action of GABA during GDPs. We provide evidence also that, at these connections, cyclic AMP-dependent protein kinase A (PKA) is the signaling molecule necessary for enhancing synaptic efficacy, since GDPs-induced potentiation was prevented by the membrane permeable PKA inhibitor (PKI 14-22) applied in the bath or by the membrane impermeable form of PKI (PKI 6-22) applied via the patch pipette. In conclusion, it is suggested that GDPs translate specific patterns of pre- and postsynaptic activity into long-lasting changes in synaptic strength and stabilize synaptic connections, thus contributing to the structural refinement of the hippocampal circuit. PMID- 17725506 TI - Oscillatory circuits underlying locomotor networks in the rat spinal cord. AB - The mammalian thoracolumbar spinal cord contains all the necessary elements to generate a rhythmic oscillatory activity that is transformed into locomotor commands to agonist and antagonist limb muscles to produce gait at various speed. This motor program is produced by interneurons in the ventral horn and can be readily recorded even with in vitro spinal cord preparations isolated from rats or mice (once dorsal afferents are stimulated or excitatory neuronchemicals applied). The locomotor program is continuously modulated and refined by afferent sensory inputs and by signals descending from brain centers. Nevertheless, this program is not the only type of rhythmic discharge produced by spinal networks. In fact, activation of metabotropic group I glutamate receptors or block of certain K+ currents by 4-aminopyridine generates non-locomotor discharges, and, at the same time, facilitates evoked locomotor activity, which then suppresses any other interfering rhythmicity. These findings suggest that accessory networks, activated by suitable stimuli, might be exploited to restore locomotor activity damaged by a lesion, an obvious goal for neuro-rehabilitation purposes. The structure of the locomotor networks appears to include a rhythm-generating circuit that drives a pattern formation circuit, commanding motoneurons to discharge appropriate signals to skeletal muscles. Studies with the K+-channel blocker tetraethylammonium have indicated that this hierarchical arrangement is preserved in vitro. Hence, isolated spinal cord preparations represent an interesting experimental tool to investigate new mechanisms to upregulate various components of locomotor networks, especially after the induction of experimental lesions. PMID- 17725507 TI - Two-deoxyglucose-induced long-term potentiation in slices of rat dentrate gyrus. AB - In keeping with previous observations in the CA1 and the somatosensory neocortex of the brain of rat, 20-min applications of 2-deoxy-D-glucose (2DG; 10 mM, replacing glucose) induced a long-term potentiation (LTP)-like enhancement of field excitatory synaptic potentials (fEPSPs) in the dentate region of hippocampal slices. The effects of 2DG were not identical at synapses of medial and lateral perforant paths (MPP and LPP). At MPP synapses, there was no post-2DG early depression of fEPSPs and the potentiation reached +78.6 +/- 5.7 % (+/- standard error of the mean) 40 min after the return to glucose. In the presence of 50 microM D-amino-phosphono valerate (APV; an N-methyl-D-aspartate [NMDA] receptor antagonist), a marked post-2DG depression appeared and the subsequent LTP was reduced to +34.7 +/- 2.8 % (for both 2DG- and APV-treatment P<0.001 by ANOVA-2W). At LPP synapses, even under control conditions, there was a sharp post 2DG depression followed by LTP (+62.2 +/- 5.7 %) and APV had little effect on either the post-2DG depression or LTP, reducing the latter by only 24 % [the 2DG treatment was very significant (P<0.001) but not the APV treatment]. Thus, 2DG evokes both NMDAR-dependent and -independent components of LTP in the perforant pathways. In view of these findings, the consumption of 2DG could have significant effects on synaptic plasticity and cognitive function. PMID- 17725508 TI - Developmental refinement in the mammalian thalamus. AB - The sensory relay synapses in the thalamus undergo extensive refinement during early life. Disruptions of spontaneous activity, but not sensory deprivation, can induce large-scale re-organization of neuronal connections in the thalamus. Recent studies also reveal an extended period of synaptic refinement in the visual and somatosensory relay synapses, where sensory deprivation produces some unexpected effects on synaptic remodeling. This article aims to provide a brief overview of recent findings and current ideas about the refinement of relay synapses in the thalamus. PMID- 17725509 TI - Molecular dynamics simulations of glutamate diffusion in synaptic cleft. AB - Diffusion of transmitters in the synaptic cleft critically influences synaptic efficacy by affecting both the amplitude and the time course of quantal events, but the value of the diffusion constant is speculative. In this study, we use molecular dynamics simulations to determine how the spatial confinement and membrane charges affect the diffusion constants of glutamate- and water as well as general properties of their diffusion. The synaptic cleft is represented as the space enclosed by two single-wall carbon sheets. Both water and especially glutamate are concentrated near the pore wall, where the concentration of glutamate can reach 30-50 times the mean value and the concentration of water can reach 2-8 times the mean value. Such spatial profiles of glutamate contradict the classical notions of diffusion on which both continuous and Monte Carlo simulations are built. The layering of glutamate- and water molecules suggests that the interfacial glutamate-cleft wall (or water-cleft wall) interactions may critically regulate their diffusion in the cleft. Indeed, the effective longitudinal diffusion constant of glutamate is steeply dependent on the cleft width, but only when the cleft is very narrow (< 5 nm). Therefore, even for a cleft as narrow as at the glutamatergic synapse in the central nervous system, the effective diffusion constant of glutamate will not be much lower than free diffusion in the bulk solution due to confinement. The effective diffusion constant of water is considerably less sensitive to cleft width over the same range of cleft widths than is glutamate, but is also higher than that of glutamate. Finally, the layering of glutamate and water and their effective diffusion constants are largely independent of how the cleft wall is charged. In conclusion, in the confined space of the synaptic cleft, glutamate is layered near the wall. Consequently, its diffusion constant becomes dependent on the cleft width. However, the diffusion of glutamate is slower than its free diffusion in water only if the cleft is very narrow. If the width of the cleft is consistent with that determined by morphometric studies in the central nervous system, glutamate diffusion should not be slowed by confinement and is thus likely to be similar to that in free solution. PMID- 17725510 TI - Hippocampal long-term synaptic plasticity and signal amplification of NMDA receptors. AB - The direction of plasticity at CA3-CA1 hippocampal synapses is determined by the strength of afferent stimulation. Weak stimuli lead to long-term depression (LTD) and strong stimuli to long-term potentiation (LTP), but both require activation of synaptic N-methyl-D-aspartate receptors (NMDARs). These receptors are therefore necessary and required for the induction of plasticity at CA3-CA1 synapses even though they carry little of the current responsible for the basal excitatory post-synaptic potential (EPSP). The influx of Ca(2+) via NMDARs triggers the subsequent and persistent changes in the expression of alpha-amino-3 hydroxy-5 methylisoxazole-4-proprionic acid receptors (AMPARs) and these receptors are responsible for the major part of the basal EPSP. The degree of activity of NMDARs is determined in part by extracellular Mg(2+) and by the co agonists for this receptor, glycine and D-serine. During strong stimulation, a relief of the voltage-dependent block of NMDARs by Mg(2+) provides a positive feedback for NMDAR Ca(2+) influx into postsynaptic CA1 spines. In this review, we discuss how the induction of LTP at CA3-CA1 synapses requires further signal amplification of NMDAR activity. We discuss how the regulation of NMDARs by protein kinases and phosphatases is brought into play. Evidence is presented that Src family kinases (SFKs) play a "core" role in the induction of LTP by enhancing the function and expression of NMDARs. At CA3-CA1 synapses, NMDARs are largely composed of NR1 (NMDA receptor subunit 1)-NR2A or NR1-NR2B containing subunits. Recent, but controversial, evidence has correlated NR1-NR2A receptors with the induction of LTP and NR1-NR2B receptors with LTD. However, LTP can be induced by activation of either subtype of NMDAR and the ratio of NR2A:NR2B receptors has been proposed as an alternative determinant of the direction of synaptic plasticity. Many transmitters and signal pathways can modify NMDAR function and expression and, for a given stimulus strength, they can potentially lead to a change in the balance between LTP and LTD. As opposed to the "core" mechanisms of LTP and LTD, the resulting alterations in this balance underlie "meta plasticity." Thus, in addition to their contribution to core mechanisms, we will also discuss how Src-family kinases could preferentially target NR1-NR2A or NR1 NR2B receptors to alter the relative contribution of these receptor subtypes to synaptic plasticity. PMID- 17725511 TI - Cocaine inhibition of GABA(A) current: role of dephosphorylation. AB - Acute cocaine toxicity is frequently associated with seizures. The mechanisms underlying the convulsant effect of cocaine are not well understood. Previously, we have shown that cocaine depresses whole-cell current evoked by gamma aminobutyric acid (GABA) in hippocampal neurons freshly isolated from rats. Cocaine's effect was voltage-independent and concentration-dependent. In the present study, using whole-cell patch-clamp recording on rat neurons freshly isolated from hippocampus, we examined the intracellular mechanisms involved in cocaine's action. Increasing intracellular Ca(2+) concentration ([Ca]i) from 0.01 to 5 microM strongly increased the depressant effect of cocaine. By contrast, 1 [N, O-bis (5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN 62), a specific antagonist of Ca/calmodulin-dependent protein kinase (CaMKII), attenuated or enhanced cocaine's action in different neurons: in three out of nine neurons dialysed with 5 microM KN-62,1 mM cocaine depressed GABA current by only 33%, but in another three out of nine neurons, cocaine depressed GABA current by as much as 83%. Chelerythrine (a specific CaCa(2+)/phospholipid dependent protein kinase C [PKC] antagonist) had minimal effect on cocaine's action. We suggest that cocaine induces an increase in [Ca]i, which stimulates phosphatase activity and thus leads to dephosphorylation of GABA receptors. This dephosphorylation-mediated disinhibitory action may play a role in cocaine induced convulsant states. PMID- 17725512 TI - Surviving anoxia: a tale of two white matter tracts. AB - Successful axon function is vital to the overall performance of the central nervous system (CNS). White matter (WM) axons are dependent on constant supply of oxygen and glucose to transmit signals with high fidelity. The optic nerve is a pure WM tract composed of completely myelinated axons while corpus callosum (CC) slices contain both gray and WM portions of the brain with a mixture of myelinated and unmyelinated axons. Axon function in both WM tracts is resistant to anoxia with a subset of axons able to survive exclusively on energy generated by glycolysis. In mouse optic nerves (MONs), removal of glucose during anoxia causes complete loss of axon function, implicating glucose as the sole source of energy. In contrast, in rat optic nerve (RON), anoxia causes rapid and complete loss of function. Because RON is about twice the diameter of MON, glucose diffusion during anoxia is inadequate. Increasing bath glucose concentration restores the ability of RON axons to persist during anoxia. Although in 10 mM glucose, MONs and CC slices exhibit identical resistance to anoxia, 30 mM glucose unmasks the greater resistance of CC axons suggesting unmyelinated axons and/or the smallest axons with the thinnest myelin sheath are resistant to anoxia. These results reveal that CNS WM is remarkably tolerant of anoxia although there is regional variability in their ability to function and survive anoxia. To achieve optimal protection of the CNS in various neurological diseases, it is critical to understand the properties of regional energy metabolisms and injury mechanisms for successful therapeutic approaches. PMID- 17725513 TI - GABA neurotransmission and neural cation-chloride co-transporters: actions beyond ion transport. AB - During neuronal development, gamma-aminobutyric acid (GABA), which is the principal inhibitory neurotransmitter in the mature brain, exerts a paradoxical depolarizing action that plays an important role in the generation of neuronal synaptic activities in the immature cortical structures and in the formation of the neuronal network. The depolarizing action of GABA is due to a differential organization of the chloride homeostasis system; in immature neurons it maintains an elevated intracellular chloride concentration ([Cl-]i), whereas in mature neurons it keeps [Cl-]i at relatively low levels. Several recent studies have shown that the function of chloride transporters during neuronal development extends beyond the simple maintenance of chloride homeostasis and might play an active role in neuronal growth and formation of synaptic connections. In the present manuscript, we summarize such evidence and discuss the perspectives in the study of the functional role of ion transporters in determining the mode of GABA actions. PMID- 17725514 TI - Endocannabinoid signaling and synaptic plasticity in the brain. AB - Repetitive firing neuron or activation of synaptic transmission plays an important role in the modulation of synaptic efficacy, such as long-term potentiation (LTP) and long-term depression (LTD). These activity-dependent changes in synaptic efficacy are thought to be critical to learning and memory; however, the underlying mechanisms remain to be defined. Endogenous cannabinoids (eCBs) are diffusible modulators that are released from depolarized postsynaptic neurons and act on presynaptic terminals. Persistent release of eCBs can lead to long-term modulation of synaptic plasticity in the brain. Given a broad distribution of eCB receptors in the brain, the eCB signaling system could contribute to use-dependent modification of brain functions. PMID- 17725515 TI - Homeostatic plasticity: comparing and contrasting cortical and hippocampal studies. A review. AB - Homeostatic plasticity is an important physiological process in the mammalian nervous system. In this review, we discuss methodological and mechanistic similarities and differences in cortical and hippocampal studies of homeostatic plasticity. Although there are many similarities, there are also region-specific differences in the effects and/or mechanisms that regulate homeostatic plasticity in these two regions. In this review, we propose a new experimental paradigm to study homeostatic plasticity that may address some unanswered questions in the field. PMID- 17725516 TI - Seizures beget seizures: the quest for GABA as a key player. AB - Synapses mediated by gamma-aminobutyric acid (GABA) A receptors are notoriously altered during periods of enhanced activity. Since a loss of inhibitory tone is a basic cause of seizures and epilepsies, it is important to determine the underlying mechanisms and the way this could be alleviated or at least reduced. Alterations of the intracellular content of chloride are thought to be a major player in the sequence of events that follow episodes of hyperactivity. In this review, I discuss these mechanisms both in the adult and developing brain, relying on studies in which chloride and GABAergic currents were measured by electrophysiological and imaging techniques. The main conclusion is that in adult systems, status epilepticus induces a complete re-organization of the networks, with cell death, axonal growth, and glutamatergic neosynapse formation leading to an increased glutamatergic drive. This, in turn, will decrease the threshold of seizure generation and thus contribute to seizure generation. In contrast, GABAergic synapses are not readily "plastic" as the lost interneurones and synapses are not replaced. Somatostatin-positive 0-LM Interneurons that innervate the dendrites of the principal cells in the hippocampus degenerate selectively, leading to a loss of the inhibitory drive in the dendrites, whereas somatic projecting basket cells and somatic inhibitory drives are relatively spared. This imbalance leads to a reduction of the inhibitory strength that is necessary but not sufficient to generate ongoing seizures. An additional important factor is the persistent increase of the intracellular chloride concentration that leads to a long-lasting shift in the depolarizing direction of the actions of GABA that will also contribute to seizure generation. In the developing brain, a major source of seizure generation is the depolarizing and often excitatory actions of GABA due to a higher intracellular chloride concentration ([Cl-]I) in immature neurons, a property that has been confirmed in all developing systems and animal species studied. As a consequence, immature GABAergic synapses will excite targets and facilitate the emergence of seizures, in keeping with the well-known higher incidence of seizures in the developing brain. Using a unique preparation with two intact hippocampi placed in a three-compartment chamber in vitro, we have provided direct evidence that seizures beget seizures and that GABA signaling plays a central role in this phenomenon. Indeed, recurrent seizures triggered in one hippocampus by a convulsive agent propagate to the other hippocampus and transform the naive hippocampus into one that generates seizures once disconnected from the other hippocampus. This transformation is conditioned by the occurrence during the seizures of high-frequency oscillations (40 Hz and above). Interestingly, these oscillations are only produced when N-methyl-D aspartate (NMDA-) and GABA receptors are operative and not blocked in the naive hippocampus. Therefore, GABA-receptor antagonists are pro-convulsive in the developing brain but, in fact, anti-epileptic. This paradoxical conclusion has quite a few clinical implications that are discussed. PMID- 17725517 TI - Inflammation in ischemic brain injury: timing is important. AB - Inflammation is a defense reaction against diverse insults that serves to remove noxious agents and to limit their detrimental effects. There is increasing evidence that post-ischemic inflammation plays an important role in brain ischemia. However, whether inflammatory processes are deleterious or beneficial to recovery is presently a matter of debate and controversy. Experimentally and clinically, stroke is followed by an acute and a prolonged inflammatory response characterized by the production of inflammatory cytokines, leukocyte and monocyte infiltration in the brain, and the activation of resident glial cells. These events may contribute to ischemic brain injury. Several groups report conflicting results regarding the role of inflammation and effects of anti-inflammatory treatments in cerebral ischemia. Experimental studies employing knockout mice for different cytokines and chemokines provide only partial answers. This highlights the importance of clarifying the role of the immune response in pathological changes at the site of ischemic lesions in the brain. Here, we describe dual effects of the brain's inflammatory response and new evidence for a neuroprotective role of proliferating microglial cells in ischemia. In addition, we discuss a potential role of post-ischemic inflammation in brain regeneration and modulation of synaptic plasticity. PMID- 17725518 TI - Regulation of hippocampal sharp waves by Ca2+-dependent slow after hyperpolarization. AB - In rodent hippocampal pyramidal neurons, repetitive discharges are followed by a slow afterhyperpolarization (sAHP) as a result of activation of a Ca2+-dependent K+ current. The sAHP is sensitive to activation of several G-protein coupled neurotransmitter receptors and downstream signal cascades. Modulations of the sAHP have been shown to be closely associated with synaptic plasticity, learning, and aging processes. However, it is presently unclear whether the sAHP generation is involved in hippocampal network activities. We explored this issue using an in vitro (thick-slice) model of mouse hippocampal sharp waves. Our data show that the sAHP occurs in CA3 pyramidal neurons following each sharp wave event and sAHP suppression is associated with a large increase in occurrence frequency of spontaneous sharp waves. Considering that sharp waves are important for hippocampal-cortical communication and memory processes, we postulate that the sAHP serves as an intrinsic regulatory mechanism of sharp waves and plays a significant role in hippocampus-dependent cognitive functions. PMID- 17725519 TI - Low-threshold-activated Ca channels: from molecules to functions: over 25 years of progress. AB - Once the tools for controlling calcium gradients became available to electrophysiologists, they began the quest for understanding the role of Ca2+ in the control of neuronal activity. In the early 1970s Paul Feltz and I spent a rich period in K. Krnjevic's laboratory in Montreal, and I was already involved in a research, which showed that an increase in intracellular Ca2+ concentration can lead to hyperpolarization of motoneurones. At about the same time, a potassium conductance activated by intracellular calcium injection was identified in mammals and snails. Since then, most of my work has dealt with the study of Ca2+ entry in neurons. Here I review the progress that led fi rst to the biophysical characterization and, later, to the molecular identification of T type calcium channels. With the advent of new optical methods, in particular two photon microscopy, we may be on the brink of a step forward in our understanding of how T channels play a role in the integrative processes that take place in a large cortical neuron such as the Purkinje cell. PMID- 17725520 TI - The mouse cerebellar cortex in organotypic slice cultures: an in vitro model to analyze the consequences of mutations and pathologies on neuronal survival, development, and function. AB - Thin acute slices and dissociated cell cultures taken from different parts of the brain have been widely used to examine the function of the nervous system, neuron specific interactions, and neuronal development (specifically, neurobiology, neuropharmacology, and neurotoxicology studies). Here, we focus on an alternative in vitro model: brain-slice cultures in roller tubes, initially introduced by Beat Gahwiler for studies with rats, that we have recently adapted for studies of mouse cerebellum. Cultured cerebellar slices afford many of the advantages of dissociated cultures of neurons and thin acute slices. Organotypic slice cultures were established from newborn or 10-15-day-old mice. After 3-4 weeks in culture, the slices flattened to form a cell monolayer. The main types of cerebellar neurons could be identified with immunostaining techniques, while their electrophysiological properties could be easily characterized with the patch clamp recording technique. When slices were taken from newborn mice and cultured for 3 weeks, aspects of the cerebellar development were displayed. A functional neuronal network was established despite the absence of mossy and climbing fibers, which are the two excitatory afferent projections to the cerebellum. When slices were made from 10-15-day-old mice, which are at a developmental stage when cerebellum organization is almost established, the structure and neuronal pathways were intact after 3-4 weeks in culture. These unique characteristics make organotypic slice cultures of mouse cerebellar cortex a valuable model for analyzing the consequences of gene mutations that profoundly alter neuronal function and compromise postnatal survival. PMID- 17725521 TI - Translational control of long-term synaptic plasticity and memory storage by eIF2alpha. AB - Both long-lasting changes in synaptic function and long-term memory require gene expression. However, the molecular mechanisms by which gene expression is turned on are not fully understood. In this review, we highlight the role of the eukaryotic initiation factor 2 alpha (eIF2alpha) signalling pathway in long-term synaptic plasticity and memory. PMID- 17725522 TI - A key glycolytic enzyme plays a dual role in GABAergic neurotransmission and in human epilepsy. AB - We have previously described a new endogenous phosphorylation mechanism that maintains ionotropic gamma-aminobutyric acid receptor (GABAAR) function and have shown that the kinase involved is the glycolytic enzyme glyceraldehyde-3 phosphate dehydrogenase (GAPDH). This enzyme is closely associated with the receptor and phosphorylates the alpha1 subunit of the receptor. In a wealth of studies, a reduction in GABAergic neurotransmission has been suggested as a pathophysiological mechanism for human epilepsy. In this paper, we present evidence showing both reduced efficacy of this glycolysis-dependent GABAAR phosphorylation mechanism and of GABAergic inhibition in epileptogenic cortical tissue samples obtained during curative surgery of patients with partial seizures, as compared to non-epileptogenic human cortical tissue. This feature is not due to a reduction in the density of GABAAR alpha1 subunits in the epileptogenic tissue as evidenced by photoaffinity labeling. Maintaining the receptor in a phosphorylated state either by favoring the endogenous phosphorylation or by inhibiting a membrane-bound phosphatase sustains the GABAAR responses in the human epileptogenic cortex. The deficiency in endogenous phosphorylation and the associated decreased GABAAR function can account for transient failures of GABAergic inhibition and may favor seizure initiation and propagation. These findings suggest a functional link between epileptic pathology and the regional cerebral glucose hypometabolism observed in patients with partial epilepsies, since the dysfunction of the GABAergic mechanism is dependent on locally produced glycolytic ATP. They also point to new targets for developing molecules active in drug-resistant epilepsies. PMID- 17725524 TI - Therapeutic opportunities in colon-specific drug-delivery systems. AB - Oral colon-specific drug-delivery systems have recently gained importance for delivering a variety of therapeutic agents. The major obstacles to delivering drugs to the colon are the absorption and degradation pathways in the upper gastrointestinal tract. However, a successfully designed colon-targeted system can overcome these obstacles. Targeting drugs to the colon has proven quite valuable in a variety of disorders, and the colon has proven to be a potential site for local as well as systemic administration of drugs. Colon targeting has proven beneficial for local action in a variety of disease conditions, such as inflammatory bowel disease, irritable bowel syndrome, and colonic cancer. Aminosalicylates, corticosteroids, immunosuppressive agents, cationized antioxidant enzymes, genetically engineered bacteria to produce cytokines, nicotine, and other drugs have exhibited significantly enhanced efficacy when delivered to the colon. Targeting drugs to cancer cells through receptors and ligands have opened up new avenues in the treatment of colonic cancer. Colon targeting has also proven useful for systemic action of protein-peptide drugs such as insulin, calcitonin, and met-enkaphalin and even for other nonpeptide drugs such as cardiovascular and antiasthmatic agents. This review also presents various approaches for targeting orally administered dosage forms to the colon. The use of a prodrug approach, bioadhesive polymers, and coating with pH sensitive and biodegradable polymers has been, to an extent, highly successful in delivering the targeted formulations to the site of action. Biodegrable hydrogels such as amylose, chondroitin sulphate, chitosan, inulin, guar gum, and pectin have also been successfully used to achieve oral colon-targeted delivery. PMID- 17725525 TI - Effects of hexaammine cobalt (III) chloride on oxidative stress-related parameters and drug metabolizing enzymes in mice. AB - Hexaammine cobalt (III) chloride has been advocated as a potential anticarcinogenic compound. There is no information on the effects of this compound on oxidative stress-related parameters in animals. In the present study the effects of administration of hexaammine cobalt (III) chloride in drinking water to balb/c male mice at doses of 25, 50, and 100 ppm for 14 weeks were examined. The tissue distribution of the compound was seen in liver, kidney, lung, intestine, blood, and spleen. The effects of the compound were monitored on levels of lipid peroxidation, GSH content, and activities of SOD, catalase, GST, and Cyt P450, along with the liver and kidney function tests. The results show that the cobalt accumulated maximally in kidney followed by liver, intestine, blood, spleen, and lung in decreasing order, in a dose-dependent manner. GSH and GST also showed increase in a dose-dependent manner while SOD and catalase showed increase with the highest dose only. Liver and kidney function tests showed no untoward change with any dose at the end of the study. The results suggest an antioxidant potentiating effect of the hexaammine cobalt (III) chloride besides nontoxicity to liver and kidney. Since the ability to induce an increase of GSH and GST along with other detoxifying enzymes by anticarcinogenic agents has been reported to correlate with the inhibition of tumorigenesis, the cobalt complex might qualify as a potential cancer chemopreventive agent. PMID- 17725526 TI - Abrogation of thioacetamide-induced biochemical events of hepatic tumor promotion stage by tannic acid in Wistar rats. AB - Tannic acid is present in almost every edible plant and is generally used as a safe food additive. In this study we investigated the antioxidative and antihyperproliferative potential of tannic acid against thioacetoamide (TAA), a potent hepatotoxic-substance-induced oxidative stress and hyperproliferation biomarker. We have shown here that the activities of hepatic antioxidant enzymes, phase II metabolizing enzymes, and the glutathione content were decreased while hepatic ornithine decarboxylase activity and DNA synthesis were induced in TAA treated animals. Tannic acid administration at two different doses prior to the TAA injection partially recovered the depleted level of glutathione, inhibited activities of antioxidant and phase II metabolizing enzymes, and resulted in significant inhibition of oxidative stress in a dose-dependent manner. Tannic acid administration before TAA treatment also resulted in a significant decrease in ODC activity and [3H]-thymidine incorporation in rat liver, which are classical markers of inflammation and tumor promotion. Our data clearly demonstrate that tannic acid possesses antioxidant and antiproliferating activities because it inhibits early biomarkers of TAA-induced tumor promotion in an in vivo animal model. PMID- 17725527 TI - The effects of combined alpha-tocopherol, ascorbic acid, and selenium against cadmium toxicity in rat intestine. AB - In this study, the effects of combined antioxidants treatment against cadmium toxicity were investigated microscopically, immunohistochemically, and biochemically in small intestine of Sprague Dawley rats. The rats were subdivided into four groups as intact control, cadmium was administrated, and both control and cadmium groups treated with ascorbic acid, alpha-tocopherol, and selenium. Metallothionein expression was localized in the base of intestinal glands in control rats and similar expression was observed with antioxidants treatment. In cadmium-administrated rats, metallothionein expression was detected in surface epithelium, longitudinal muscle layer, meissner, and myenteric plexuses, but not in the base of intestinal gland. On the other hand, in the rats treated with antioxidants and cadmium, immunreactivity increased in the surface epithelium and in the base of intestinal glands according to cadmium-administrated rats but not changed in the plexuses and longitudinal muscle layer. Biochemically, lipid peroxidation levels increased and glutathione levels decreased significantly in intestine of the cadmium group compared to the control. Treatment with antioxidants in cadmium-administrated rats led to a decrease in lipid peroxidation levels and a significant increase in glutathione levels. As a result, the combination of ascorbic acid, alpha-tocopherol, and selenium shows a protective effect against cadmium toxicity in small intestine. PMID- 17725528 TI - Investigation on the genotoxic effects of long-term administration of sodium arsenite in bone marrow and testicular cells in vivo using the comet assay. AB - The main source of environmental arsenic exposure in most populations is drinking water in which inorganic forms of arsenic predominate. The single-cell gel electrophoresis technique (the comet assay) measures DNA damage, including double strand and single-strand breaks, in somatic cells after a variety of genotoxic insults. We have used this method to measure damage to cellular DNA in the bone marrow and testicular cells of mice using the alkaline comet assay for the former and neutral comet assay for the latter. Swiss albino male mice were exposed to sodium arsenite in drinking water at concentrations of 10, 50,100, and 200 mg/l for a period of three months. Concurrently, negative and positive control sets were maintained. The negative control animals were given distilled water as drinking water for the same period of treatment while the animals in positive control sets were either given single or multiple injections of EMS (100 mg/kg body weight) according to the tissue sampled. Following long-term exposure, there was a significant dose-dependent reduction in the size and weight of testes. The comet parameters of DNA, such as tail length (microm), % of DNA in tail, and Olive tail moment (arbitrary units) were increased in both bone marrow and testicular cells due to arsenic-induced DNA strand breaks. A positive dose response relationship was noted. The magnitude of DNA strand break was more pronounced in the bone marrow cells than in the testicular cells. The minimum effective concentrations for inducing DNA damage in bone marrow cells and testicular cells were 10 mg/l and 50 mg/l, respectively. The results of the study indicate that arsenic in drinking water is genotoxic in mice and the comet assay can be used for examining DNA damage in testicular cells as a parameter for evaluating male reproductive toxicity. PMID- 17725523 TI - Gene modulation for treating liver fibrosis. AB - Despite tremendous progress in our understanding of fibrogenesis, injury stimuli process, inflammation, and hepatic stellate cell (HSC) activation, there is still no standard treatment for liver fibrosis. Delivery of small molecular weight drugs, proteins, and nucleic acids to specific liver cell types remains a challenge due to the overexpression of extracellular matrix (ECM) and consequent closure of sinusoidal gaps. In addition, activation of HSCs and subsequent release of inflammatory cytokines and infiltration of immune cells are other major obstacles to the treatment of liver fibrosis. To overcome these barriers, different therapeutic approaches are being investigated. Among them, the modulation of certain aberrant protein production is quite promising for treating liver fibrosis. In this review, we describe the mechanism of antisense, antigene, and RNA interference (RNAi) therapies and discuss how the backbone modification of oligonucleotides affects their in vivo stability, biodistribution, and bioactivity. Strategies for delivering these nucleic acids to specific cell types are discussed. This review critically addresses various insights developed with each individual strategy and for multipronged approaches, which will be helpful in achieving more effective outcomes. PMID- 17725529 TI - Genotoxic and oxidative damage induced by Helicobacter pylori in Meriones unguiculatus. AB - Infection with Helicobacter pylori has been shown to be at the origin of various gastric pathologies. However, it has not yet been established whether the etiology of such diseases, particularly of gastric cancer, is related to the production of free radicals or to mutagenesis. The aim of this study was to determine whether a six-month infection with Helicobacter pylori increased the amount of lipid peroxidation, nitric oxide, and DNA damage in Mongolian gerbils (Meriones unguiculatus). H. pylori was characterized genotypically and administered orally to the animals. Four tests were applied to identify the presence of bacteria at one, two, four, and six months after the inoculation, namely, isolation and identification in culture, the urease test, the ELISA assay, and immunohistochemical staining of gastric biopsies. The infection was considered to be successful when three of the above-mentioned tests were positive. The infection occurred in 30% of the animals in the first month after the H. pylori inoculation and in 60-70% of the animals in the later stages. Levels of malondialdehyde, nitric oxide, and DNA damage (using the "comet" assay) were determined in the gastric tissue of the animals at one, two, four, and six months. We found statistically significant increases in malondialdehyde and nitric oxide levels from the second month on. The comet assay in animals infected with H. pylori showed a significant increase in the mean tail length throughout the observation period. We conclude that our results support the assumption that oxidative damage and DNA breakage produced by the infection with H. pylori are some of the initial alterations occurring in the development of gastric diseases. PMID- 17725530 TI - Gene expression profiling of di-n-butyl phthalate in normal human mammary epithelial cells. AB - Studies show that female workers in the personal-care industry have an increased risk of developing cancer believed to be the result of increased exposure to toxic and/or carcinogenic chemicals found in cosmetics, hair dyes, and nail polish. One chemical found in multiple personal-care products, di-n-butyl phthalate (DBP), is a known endocrine disruptor and has been found in increased levels in women of childbearing age. The goal of this study was to elucidate mechanisms of phthalate toxicity in normal human cells to provide information concerning interindividual variation and gene-environment interactions. Normal human mammary epithelial cell strains were obtained from discarded tissues following reduction mammoplasty [Cooperative Human Tissue Network (sponsors: NCI/NDRI)]. Gene transcription in each cell strain was analyzed using high density oligonucleotide DNA microarrays (U133A, Affymetrix) and changes in the expression of selected genes were verified by real-time polymerase chain reaction (PCR) (ABI). DNA microarrays were hybridized with total RNA that was collected after DBP treatment for 5 hr and 10 hr. RNA was harvested from the vehicle control (acetone) at 10 hr. Data Mining Tool software (Affymetrix) was used to separate genes in clusters based on their expression patterns over time. Only 57 genes were found to be altered in all four cell strains following exposure to DBP. These included genes involved in fertility (inhibin, placental growth factor), immune response (tumor necrosis factor induced protein), and antioxidant status (glutathione peroxidase). Data from this study will help clarify the role of DBP in reproductive toxicity, and yield biomarkers of exposure for future epidemiology studies. PMID- 17725531 TI - Induction of apoptosis by calcium D-glucarate in 7,12-dimethyl benz [a] anthracene-exposed mouse skin. AB - Calcium glucarate (Cag), a naturally occurring nontoxic compound, suppresses the DMBA-induced tumor development in mouse skin. In the process of understanding the mechanisms of tumor suppression by Cag, we investigated the effect of topical application of Cag on selective and critical events of apoptotic pathway in DMBA exposed mouse epidermis. Varied doses of DMBA or Cag were used for the study. DMBA had an inhibitory effect on proteases in general and on caspases in particular. Cag tried to reverse the inhibitory effect of DMBA on 3, 8, or 9 caspase in a dose-dependent manner. Cag inhibited activity of Poly ADP-ribose polymerase enzyme, a substrate of caspses, after DMBA exposure. As indicated by western blotting, Cag treatment also inhibited PARP expression induced by DMBA at the level of protein. Cag induced the DMBA-inhibited Ca++/Mg++-dependent endonuclease, an enzyme responsible for the DNA fragmentation during apoptosis. DMBA induced the expression of mutant-p53 and Bcl-2. This induced expression of proteins was reversed when Cag was given along with DMBA. Cag showed a dose dependent inhibition of DMBA-induced mutant-p53 expression. Similarly Bcl-2 overexpression by DMBA was also inhibited by topical treatment of Cag when given along with DMBA. Inhibition of mutant-p53 and Bcl-2 expression by Cag in DMBA exposed mouse skin might contribute to the apoptogenic effect possibly exerted by Cag while suppressing the tumor development. The study indicates that Cag induces apoptosis in mouse epidermis, a possible mechanism for tumor suppression, and thus could be considered a promising anticancer agent. PMID- 17725534 TI - Cell-substrate topology upon ALA-PDT using variable-angle total internal reflection fluorescence microscopy (VA-TIRFM). AB - Because of the low penetration depth of an evanescent electromagnetic field, total internal reflection fluorescence microscopy (TIRFM) proved to be a powerful technique to examine fluorescent dyes or photosensitizers in close vicinity to the plasma membrane of living cells. In addition, on variation of the angle of incidence of exciting laser light, the penetration depth is varied, so that cell substrate topology can be examined with nanometer resolution. Using a specific illumination device for TIRFM and a highly sensitive electron multiplying (EM) CCD camera, fluorescence of the photosensitizer protoporphyrin IX (PPIX) was studied in human cancer cells after application of 5-aminolevulinic acid (5-ALA) prior to and after irradiation with sublethal light doses (635 nm, 4 J/cm2). For cells growing on microscope cover slides, cell-substrate distances varied between approximately 20 and 250 nm with a mean distance of approximately 120 nm. On light exposure, these distances generally decreased, and a mean value below 100 nm was attained. Moreover, focal contacts visualized with a fusion protein of yellow fluorescent protein and focal adhesion kinase were maintained on light exposure, i.e., light-induced detachment of cells from their substrate was not likely to occur. PMID- 17725533 TI - 5-aminolevulinic acid-mediated photodynamic therapy on Hep-2 and MCF-7c3 cells. AB - The cytotoxic effect of 5-aminolevulinic acid (ALA) induced protoporphyrin IX (PPIX) on two human carcinoma cell lines, MCF-7c3 cells and Hep 2 cells, was studied. In both cell lines, PPIX content depends on the ALA concentration and incubation time. The maximal PPIX content was higher in the MCF-7c3 cells, reaching a value of 8 microg/10(6) cells, compared to the Hep-2 cells, which accumulated 3.2 microg/10(6) cells. Treatment of cells with the iron chelator desferrioxamine prior to ALA exposure enhances the amount of PPIX, consequently diminishing enzymatic activity of ferroquelatase. Photo sensitization of the cells was in correlation with the PPIX content; therefore, conditions leading to 80% cell death in the MCF-7c3 cells provoke a 50% cell death in the Hep 2 cells. Using fluorescence microscopy, cell morphology was analyzed after incubation with 1 mM ALA during 5 hr and irradiation with 54 Jcm(-2); 24 hr post-PDT, MCF-7c3 cells revealed the typical morphological changes of necrosis. Under the same conditions, Hep-2 cells produced chromatine fragmentation characteristic of apoptosis. PPIX accumulation was observed to occur in a perinuclear region in the MCF-7c3 cells; while in Hep-2 cells, it was localized in lysosomes. Different mechanisms of cell death were observed in both cell lines, depending on the different intracellular localization of PPIX. PMID- 17725535 TI - Biochemical manipulation via iron chelation to enhance porphyrin production from porphyrin precursors. AB - Topical protoporphyrin IX (PPIX) induced photodynamic therapy (PDT) of basal cell carcinoma (BCC) produces good clinical outcomes with excellent cosmesis as long as the disease remains superficial. Efficacy for nodular BCC, however, appears inferior to standard treatment unless repeat treatments are performed. Enhancement is therefore required and may be possible by employing iron chelating agents to temporarily increase PPIX accumulation above the levels normally obtained using aminolaevulinic acid (ALA) or the methyl ester of ALA (MAL) alone. In vitro studies investigated the efficacies of the novel iron chelator, CP94 (1,2-diethyl-3-hydroxypyridin-4-one hydrochloride), and the established iron chelator, desferrioxamine (DFO), at increasing PPIX fluorescence in cultured human lung fibroblasts and squamous carcinoma cells incubated with ALA/MAL. CP94 was found to produce greater PPIX fluorescence when administered with ALA/MAL than either congener could produce alone. CP94 was also found to be superior to DFO in the enhancement of PPIX fluorescence and could be employed to accumulate the same levels of PPIX within a shorter time period. Clinical utilization of CP94 to enhance ALA/MAL-PDT could potentially result in greater PPIX accumulation or alternatively could be employed to reduce the length of the required drug light interval. Clinical investigation of this is currently underway. PMID- 17725536 TI - Innovative drug delivery strategies for topical photodynamic therapy using porphyrin precursors. AB - Photodynamic therapy (PDT) has been extensively investigated as a treatment for tumors and neoplasias of the skin, bladder, mouth, and female reproductive tract. The most convenient drug delivery route, when focusing on the photodynamic treatment of such tumors and neoplasia, is the transdermal. However, with the inherent "barrier function" of the stratum corneum of the skin, drugs with high molecular weight (> 500 Daltons) or extremes of polarity will find it difficult to successfully cross the skin. Therefore, preformed photosensitizers, which are generally large, highly conjugated molecules, are not commonly used in topical PDT. This has led to the idea of endogenous photosensitization using the small (167.8 Daltons), although hydrophilic, 5-aminolevulinic acid (ALA) being the most frequently employed agent in modern topical PDT. Although clinical application of ALA and its bimolecular effects within target cells remain as primary research themes, the design and evaluation of delivery systems required for effective photosensitizer administration have been less well addressed. This paper briefly reviews traditional approaches to topical delivery of ALA and its esters, and highlights several innovative strategies recently employed to increase the efficacy of ALA-PDT. PMID- 17725537 TI - Fluorescence monitoring of a topically applied liposomal Temoporfin formulation and photodynamic therapy of nonpigmented skin malignancies. AB - Meso-tetra(hydroxyphenyl)chlorin (mTHPC) (INN: Temoporfin) is a potent photodynamically active substance in clinical use today. Usually, the substance is given systemically and a known drawback with this administration route is a prolonged skin light sensitization. For the first time to our knowledge, a liposomal Temoporfin gel formulation for topical application was studied in connection with photodynamic therapy (PDT) of nonpigmented skin malignancies in humans. Intervals of 4 hr between drug administration and light irradiation were used. Sensitizer distribution within tumor and surrounding normal skin was investigated by means of point monitoring and imaging fluorescence spectroscopy before, during, and after PDT, showing high tumor selectivity. Furthermore, the bleaching of Temoporfin was studied during the PDT procedure by monitoring the fluorescence following excitation by using a therapeutic light. A 30-35% light induced photometabolization was shown. No pain occurred during or after treatment. It was also observed that the treated area did not show any swollen tissue or reddening, as is often seen in PDT using topical delta-aminolevulinic acid. On controlling the patients one week after treatment, healing progress was observed in several patients and no complications were registered. PMID- 17725538 TI - Photodynamic treatment of oral lesions. AB - Photodynamic treatment (PDT) was first started in the oral cavity in the mid 1980s. Hematoporphyrins were rapidly replaced by Photofrin and meta tetrahydroxyphenylchlorin (mTHPC) as photosensitisers of choice, and over the years these two have been approved by several health authorities for PDT. 5 aminolevulinic acid (ALA) and some dyes (e.g., toluidine and methyene blue) have also been tested. Several different nonthermal lasers have been used and lately light-emitting diodes (LEDs) have been tried. Most of the clinical treatments have been carried out on oral squamous cell carcinoma (OSSC), either primary or metastatic lesions, with good results. The treatment leaves little scarring and can be used before, in conjunction with, and adjunctive to other treatment modalities. The greatest disadvantage is that the patients are photosensitive for several weeks following systemic administration of the photosensitiser. PDT is now an accepted palliative treatment. Systemic administration of ALA has been more successful than local application in the treatment of precancerous lesions such as oral leukoplakia. PDT following topical application of photosensitiser (metylene blue and methyl-ALA) has shown improvement in cutaneous diseases of the oral mucous membrane such as oral lichen planus. The bactericidal effect of PDT has also been tested on oral plaque, but little clinical work has been performed so far. Instead of mechanical cleaning or antibiotic therapy, PDT may also play a role in dental diseases. PMID- 17725539 TI - Formulation and characterization of poly(ethylene glycol)-based, 5-aminolevulinic acid-loaded solid-dosage forms intended for photodynamic and photodiagnostic methodologies in the colorectal region. AB - Aminolevulinic acid-loaded, poly(ethylene glycol) disks prepared using three molecular weights (1000, 6000, and 10,000) were shown to be of potential for rectal administration as part of photodynamic and photodiagnostic colorectal procedures. The disk-shaped delivery system was mechanically robust, as judged by friability measurements. Calorimetric analysis confirmed that low concentrations of ALA (1% w/w) were dispersed completely throughout the PEG matrix, but higher concentrations (5% w/w and 10% w/w) formed crystalline suspensions. The molecular weight of the PEG determined the melting temperature, with PEG 1000 being suitable for melting around body temperature. The drug release kinetics were shown to be a function of both molecular weight and drug loading. Although the higher molecular weight PEG disks were resistant to surface erosion arising from an aqueous receptor phase, this effect was counterbalanced by more rapid and complete release when the ALA loading was increased. The lowest loading used (1% w/w) produced incomplete release, often not exceeding 30% of the total amount of drug. Results suggest that this simple formulation containing ALA can be administered directly to the colorectal area and is a feasible alternative to peroral dosing of ALA. PMID- 17725540 TI - Improving the management of bladder cancer with fluorescence cystoscopy. AB - Endoscopic visualization (cystoscopy) and transurethral resection are effective, well-tolerated diagnostic and treatment techniques for bladder cancer. However, it is widely recognized that cystoscopy can miss biologically important lesions, such as carcinoma in situ. Attempts to improve the effectiveness of cystoscopy are not new, but initial methods were impractical and had limited efficacy. Fluorescence cystoscopy became feasible with the discovery that intravesical administration of aminolevulinic acid (ALA) made bladder cancers fluoresce when exposed to blue light. More recently, the creation of a hexyl ester of ALA (HAL) made this technique practical, because HAL significantly shortens the amount of time needed for drug exposure prior to cystoscopy. Not surprisingly, studies have shown that fluorescence cystoscopy can reveal carcinoma in situ that is visually occult under conventional (white-light) cystoscopy. An unexpected finding was that fluorescence cystoscopy also enhanced the detection of papillary tumors. Studies with ALA have shown that resection of bladder cancer with fluorescence results in improved disease-free survival compared to conventional resection under white light. This report summarizes some of the recent studies of fluorescence cystoscopy in bladder cancer. PMID- 17725541 TI - Utility of the F98 rat glioma model for photodynamic therapy. AB - A syngeneic rat brain tumor model consisting of F98 glioma cells in Fischer rats was investigated for its utility in PDT studies. Results of in vitro studies demonstrated that the F98 cell line was sensitive to ALA-PDT, especially at low light irradiances. Histological examination revealed that F98 tumors share many fundamental characteristics with human GBMs, including rapid growth and infiltrative behavior. ALA-PDT in normal brain showed that high light fluences (26 J) delivered at relatively low powers (10 mW) are capable of causing significant edema. These findings suggest that light irradiation parameters should be chosen carefully when treating tumor-bearing animals. Rats inoculated with F98 cells preincubated in ALA showed a significant survival advantage following light exposure. Taken together, the results suggest that the F98 rat glioma model is appropriate for PDT studies of malignant gliomas. PMID- 17725542 TI - ALA and malignant glioma: fluorescence-guided resection and photodynamic treatment. AB - BACKGROUND: Oral application of 20 mg/kg body weight of 5-aminolevulinic acid (ALA) leads to a highly specific accumulation of fluorescent Protoporphyrin IX (PPIX) in malignant glioma tissue. In the past few years, we have participated in several clinical studies designed to investigate fluorescence guided resection (FGR) and photodynamic therapy (PDT). METHODS: PPIX selectivity and PPIX bleaching during PDT were assessed with spectroscopic measurements. FGR was performed in 18 clinics in Germany (ALA-Glioma Study Group, participants see end of paper) in a phase III trial comprising an ALA group and a white-light group. PDT was performed with microlens fibers or cylindrical diffusers postsurgically to the resection bed. Additionally, a protocol for the interstitial stereotactic placement of cylindrical diffusers was established and applied on patients with recurrent, inoperable glioblastoma. RESULTS: Compared to normal cortex, mean PPIX fluorescence in vital tumor was found more than 100-fold increased. During PDT, the PPIX fluorescence bleached to 8%, 16%, and 1% of the initial intensity for the 100, 150, and 200 J/cm2 groups (median values). FGR: Contrast-enhancing tumor was completely resected in 65% of patients in the ALA group compared to 36% in the white-light group (p < 0.0001). Progression-free survival was superior in the ALA group compared to white-light patients with cumulative 6 months progression free survival rates of 41% and 21% (p = 0.0003), respectively. Interstitial PDT can be performed with multiple radial diffusers approximately 10 mm apart, 200 mW/cm, and an irradiation time of one hour. PMID- 17725543 TI - Selective inhibition of binding of Bacillus thuringiensis Cry1Ab toxin to cadherin-like and aminopeptidase proteins in brush-border membranes and dissociated epithelial cells from Bombyx mori. AB - Binding analyses with denatured epithelial membrane proteins from Bt (Bacillus thuringiensis) demonstrated at least two kinds of proteins, APNs (aminopeptidases N) and cadherin-like proteins, as possible receptors for the Cry1A class of Bt toxins. Two alternative models have been proposed, both based on initial toxin binding to a cadherin-like protein, but one involving APN and the other not. We have used two Bombyx mori strains (J65 and Kin), which are highly susceptible to Cry1Ab, to study the role of these two types of receptors on Cry1Ab toxin binding and cytotoxicity by means of the inhibitory effect of antibodies. BBMVs (brush border membrane vesicles) of strain J65 incubated with labelled 125I-Cry1Ab revealed a marked reduction in reversible and irreversible binding when anti BtR175 (a cadherin-like protein) was used for BBMV pre-treatment. By contrast, the anti-APN1 antibody specifically affected the irreversible binding, while the reversible binding component was not affected. This is the first time that binding of Cry1Ab to APN1 and to a cadherin-like protein from BBMVs in solution has been shown. Dissociated epithelial cells from the Kin strain were used to test the inhibitory effect of the antibodies on the cytotoxicity of Cry1Ab. Pre incubation of the cells with the anti-BtR175 antibody conferred protection against Cry1Ab, but not the anti-APN1 antibody. Therefore our results seem to support the two models of the mode of action of Cry1Ab in Lepidoptera, depending on whether BBMVs or intact dissociated cells are used, suggesting that both pathways may co-operate for the toxicity of Cry1A toxins in vivo. PMID- 17725544 TI - Developmentally regulated association of plastid division protein FtsZ1 with thylakoid membranes in Arabidopsis thaliana. AB - FtsZ is a key protein involved in bacterial and organellar division. Bacteria have only one ftsZ gene, while chlorophytes (higher plants and green alga) have two distinct FtsZ gene families, named FtsZ1 and FtsZ2. This raises the question of why chloroplasts in these organisms need distinct FtsZ proteins to divide. In order to unravel new functions associated with FtsZ proteins, we have identified and characterized an Arabidopsis thaliana FtsZ1 loss-of-function mutant. ftsZ1 knockout mutants are impeded in chloroplast division, and division is restored when FtsZ1 is expressed at a low level. FtsZ1-overexpressing plants show a drastic inhibition of chloroplast division. Chloroplast morphology is altered in ftsZ1, with chloroplasts having abnormalities in the thylakoid membrane network. Overexpression of FtsZ1 also induced defects in thylakoid organization with an increased network of twisting thylakoids and larger grana. We show that FtsZ1, in addition to being present in the stroma, is tightly associated with the thylakoid fraction. This association is developmentally regulated since FtsZ1 is found in the thylakoid fraction of young developing plant leaves but not in mature and old plant leaves. Our results suggest that plastid division protein FtsZ1 may have a function during leaf development in thylakoid organization, thus highlighting new functions for green plastid FtsZ. PMID- 17725545 TI - The essential role for c-Ski in mediating TGF-beta1-induced bi-directional effects on skin fibroblast proliferation through a feedback loop. AB - The bi-directional regulation of TGF-beta1 (transforming growth factor-beta1) on fibroblast proliferation with stimulation at low concentration, but inhibition at high concentration, has important significance during tissue repair. The mechanism has not been defined. c-Ski is a major co-repressor of TGF-beta1/Smad3 signalling; however, the exact role of c-Ski in the bi-directional regulation of fibroblast proliferation remains to be determined. In the present study, we established a dose-effect relationship of bi-directional regulation of TGF-beta1 mediated proliferation in rat skin fibroblasts, and found that c-Ski overexpression promoted fibroblast proliferation by inhibiting Smad3 activity. Importantly, c-Ski expression was decreased at the high concentration of TGF beta1, but increased at the low concentration of TGF-beta1. This dose-dependent change in TGF-beta1 action did not affect Smad3 phosphorylation or nuclear translocation, but altered Smad3 DNA-binding activity, transcriptional activity and expression of the downstream gene p21 that both increased at the high concentration and decreased at the low concentration. Furthermore, c-Ski overexpression exerted synergistic stimulation with TGF-beta1 at the low concentration, but reversed the inhibitory effect of TGF-beta1 at high concentrations, while knockdown of c-Ski by RNA interference abrogated bi directional role of TGF-beta1 on fibroblast proliferation. Thus our data reveal a new mechanism for this bi-directional regulation, i.e. c-Ski expression change induced by low or high TGF-beta1 concentration in turn determines the promoting or inhibiting effects of TGF-beta1 on fibroblast proliferation, and suggests an important role of c-Ski that modulates the local availability of TGF-beta1 within the wound repair microenvironment. PMID- 17725547 TI - Use of multiple fluorophores for evaluating microvascular permeability in control rats and rats with sepsis. AB - Capillary leak accompanying systemic inflammatory response conditions is a significant clinical problem. In the present study, we describe and verify a method for studying capillary leak that is based on the injection of proteins that differ significantly in size and have spectrally distinguishable fluorophores. Control (n=11) and post-CLP (caecal ligation and puncture; n=14) Sprague-Dawley rats were injected with tracer amounts of albumin and PEG-Alb [albumin covalently linked to methoxy-poly(ethylene glycol)] labelled with fluorescein and Texas Red. Blood samples were withdrawn between 5 min and 144 h, and the fluorescence of the labelled proteins was determined. The relative retention of the PEG-Alb and albumin was assessed via measurement of the TER (transcapillary escape rate; in %/h) and the t(50%) estimate, defined as the time when the actual concentration reached 50% of its baseline. The concentration-time trends for both albumin and PEG-Alb tracers exhibited two-compartmental behaviour and were analysed using bi-exponential modelling. Retention times were significantly greater for PEG-Alb in both control and CLP rats. TER(PEG-Alb) was significantly lower than TER(albumin) for both control (8.1+/-5.6 compared with 14.8+/-7.1 %/h respectively; P<0.01) and CLP (14.8+/-6.6 compared with 22.5+/-7.3 %/h respectively; P<0.001) rats. The t(50%[PEG-Alb]) was substantially greater than the corresponding t(50%[albumin]) for both control (29.8+/-9.8 compared with 7.2+/-2.0 h respectively; P<0.001) and CLP (12.9+/-5.6 compared with 5.1+/-1.6 h respectively; P<0.001) rats. The result was similar irrespective of the fluorophore-protein combination, validating the multifluorophore technique. In conclusion, the double-fluorophore approach described in the present study may provide the future basis for a method to quantify capillary leak in disease. PMID- 17725546 TI - Identification of a region on hypoxia-inducible-factor prolyl 4-hydroxylases that determines their specificity for the oxygen degradation domains. AB - HIFs [hypoxia-inducible (transcription) factors] are essential for the induction of an adaptive gene expression programme under low oxygen partial pressure. The activity of these transcription factors is mainly determined by the stability of the HIFalpha subunit, which is regulated, in an oxygen-dependent manner, by a family of three prolyl 4-hydroxylases [EGLN1-EGLN3 (EGL nine homologues 1-3)]. HIFalpha contains two, N- and C-terminal, independent ODDs (oxygen-dependent degradation domains), namely NODD and CODD, that, upon hydroxylation by the EGLNs, target HIFalpha for proteasomal degradation. In vitro studies indicate that each EGLN shows a differential preference for ODDs, However, the sequence determinants for such specificity are unknown. In the present study we showed that whereas EGLN1 and EGLN2 acted upon any of these ODDs to regulate HIF1alpha protein levels and activity in vivo, EGLN3 only acted on the CODD. With the aim of identifying the region within EGLNs responsible for their differential substrate preference, we investigated the activity and binding pattern of different EGLN deletions and chimaeric constructs generated by domain swapping between EGLN1 and EGLN3. These studies revealed a region of 97 residues that was sufficient to confer the characteristic substrate binding observed for each EGLN. Within this region, we identified the minimal sequence (EGLN1 residues 236-252) involved in substrate discrimination. Importantly, mapping of these sequences on the EGLN1 tertiary structure indicates that substrate specificity is determined by a region relatively remote from the catalytic site. PMID- 17725548 TI - Testing the growth-differentiation balance hypothesis: dynamic responses of willows to nutrient availability. AB - Here, the growth-differentiation balance hypothesis (GDBH) was tested by quantifying temporal variation in the relative growth rate (RGR), net assimilation rate (NAR), and phenylpropanoid concentrations of two willow species (Salix sericea and Salix eriocephala) across five fertility levels. Initially, RGR increased and total phenylpropanoids declined (although every individual phenolic did not) as fertility increased, but NAR was unaffected. Subsequently, NAR and phenylpropanoids declined in the low fertility treatment, generating a quadratic response of secondary metabolism across the nutrient gradient. As above and below-ground growth rates equilibrated, NAR and phenylpropanoids increased in the low fertility treatment, re-establishing a negative linear effect of fertility on secondary metabolism. A transient quadratic response of secondary metabolism is predicted when GDBH is integrated with models of optimal phenotypic plasticity, occurring when low NAR imposes carbon constraints on secondary metabolism in low nutrient environments. Once plants acclimate to nutrient limitation, the equilibrium allocation state is predicted to be a negative correlation between growth and secondary metabolism. Although both willow species generally responded according to GDBH, the complexity observed suggests that prediction of the effects of nutrient availability on secondary metabolism (and other plastic responses) in specific cases requires a priori knowledge of the physiological status of the plant and soil nutrient availability. PMID- 17725550 TI - Modifying lysine biosynthesis and catabolism in corn with a single bifunctional expression/silencing transgene cassette. AB - Although it is one of the major crops in the world, corn has poor nutritional quality for human and animal consumption due to its low lysine content. Here, we report a method of simultaneous expression of a deregulated lysine biosynthetic enzyme, CordapA, and reduction of a bifunctional lysine degradation enzyme, lysine-ketoglutarate reductase/saccharophine dehydrogenase (LKR/SDH), in transgenic corn plants by a single transgene cassette. This is accomplished by inserting an inverted-repeat sequence targeting the maize LKR/SDH gene into an intron of a transgene cassette that expresses CordapA. This combination of LKR/SDH silencing and CordapA expression led to the accumulation of free lysine to over 4000 p.p.m. in transgenic corn grain, compared to less than 100 p.p.m. in wild-type controls. This intron-embedded silencing cassette design reduces the number of transgene cassettes needed in transgenic approaches for manipulating metabolic pathways that sometimes require expression of one gene and silencing of another. PMID- 17725549 TI - Phloem-based resistance to green peach aphid is controlled by Arabidopsis PHYTOALEXIN DEFICIENT4 without its signaling partner ENHANCED DISEASE SUSCEPTIBILITY1. AB - Green peach aphid (GPA) Myzus persicae (Sulzer) is a phloem-feeding insect with an exceptionally wide host range. Previously, it has been shown that Arabidopsis thaliana PHYTOALEXIN DEFICIENT4 (PAD4), which is expressed at elevated levels in response to GPA infestation, is required for resistance to GPA in the Arabidopsis accession Columbia. We demonstrate here that the role of PAD4 in the response to GPA is conserved in Arabidopsis accessions Wassilewskija and Landsberg erecta. Electrical monitoring of aphid feeding behavior revealed that PAD4 modulates a phloem-based defense mechanism against GPA. GPA spends more time actively feeding from the sieve elements of pad4 mutants than from wild-type plants, and less time feeding on transgenic plants in which PAD4 is ectopically expressed. The activity of PAD4 in limiting phloem sap uptake serves as a deterrent in host-plant choice, and restricts aphid population size. In Arabidopsis defense against pathogens, all known PAD4 functions require its signaling and stabilizing partner EDS1 (ENHANCED DISEASE SUSCEPTIBILITY1). Bioassays with eds1 mutants alone or in combination with pad4 and with plants conditionally expressing PAD4 under the control of a dexamethasone-inducible promoter reveal that PAD4-modulated defense against GPA does not involve EDS1. Thus, a PAD4 mode of action that is uncoupled from EDS1 determines the extent of aphid feeding in the phloem. PMID- 17725551 TI - Production of soluble recombinant proteins with Kell, Duffy and Lutheran blood group antigen activity, and their use in screening human sera for Kell, Duffy and Lutheran antibodies. AB - The aim of this study was to show that soluble recombinant (sr) proteins can mimic blood group antigens and be used to screen human sera for blood-group specific antibodies. The blood of all pregnant women and pretransfusion patients should be screened for blood-group-specific antibodies to identify and monitor pregnancies at risk of haemolytic disease of the foetus and newborn (HDFN), and to prevent haemolytic transfusion reactions. Current antibody screening and identification methods use human red blood cell panels, which can complicate antibody identification if more than one antibody specificity is present. COS-7 cells were transfected to produce sr forms of the extracellular domains of the red blood cell membrane proteins that express Kell, Duffy or Lutheran blood group antigens. These sr proteins were used to screen for and identify anti-Kell, anti Duffy or anti-Lutheran blood-group-specific allo-antibodies in human sera by haemagglutination inhibition and in solid-phase enzyme-linked immunosorbent assays (ELISAs). There is a positive correlation (correlation coefficient 0.605, P value 0.002) between antibody titre by standard indirect antiglobulin test (IAT) and signal intensity in the ELISA test. This work shows that sr proteins can mimic blood group antigens and react with human allogeneic antibodies, and that such proteins could be used to develop solid-phase, high-throughput blood group antibody screening and identification platforms. PMID- 17725552 TI - Whole blood donor deferral rate and characteristics of the Turkish population. AB - Whole blood (WB) donors are deferred for several reasons, either permanently or temporarily. In this retrospective study, we quantified the rate of and reasons for donor deferral among Turkish donors. Computer records of the last 5 years were analysed to quantify the deferral rate and reasons. Deferrals were categorized as temporary short-term (1-56 days), long-term (57-365 days) and multiple years or permanent (more than 365 days). Deferred donors were also analysed according to gender, age and education level. A total of 95 317 persons were admitted for WB donation: 89.1% of them were male donors and 59.9% were in the 30 to 49-year old age category. Rates of deferral for temporary short-term, long-term, permanent or for unknown reasons were 66, 22.5, 10 and 1.5% respectively. Female donors were deferred more frequently than male donors (25.8 vs. 13.3%, P 0.05). The main reason for deferral was common cold and/or sore throat or elevated temperature (20.4%) in male donors and low haemoglobin (51.6%) in female donors. Although the three uppermost reasons for deferral in women were identical for all age categories, these varied in the male group (high risk sex partner for the younger group vs. hypertension and low haemoglobin for the older group). Although permanent and temporary deferral rates are similar between the Turkish population and western countries, leading causes vary widely. PMID- 17725553 TI - Rab6-interacting protein 1 links Rab6 and Rab11 function. AB - Rab11 and Rab6 guanosine triphosphatases are associated with membranes of the recycling endosomes (REs) and Golgi complex, respectively. Evidence indicates that they sequentially regulate a retrograde transport pathway between these two compartments, suggesting the existence of proteins that must co-ordinate their functions. Here, we report the characterization of two isoforms of a protein, Rab6-interacting protein 1 (R6IP1), originally identified as a Rab6-binding protein. R6IP1 also binds to Rab11A in its GTP-bound conformation. In interphase cells, R6IP1 is targeted to the Golgi in a Rab6-dependent manner but can associate with Rab11-positive compartments when the level of Rab11A is increased within the cells. Fluorescence resonance energy transfer analysis using fluorescence lifetime imaging shows that the overexpression of R6IP1 promotes an interaction between Rab11A and Rab6 in living cells. Accordingly, the REs marked by Rab11 and transferrin receptor are depleted from the cell periphery and accumulate in the pericentriolar area. However, endosomal and Golgi membranes do not appear to fuse with each other. We also show that R6IP1 function is required during metaphase and cytokinesis, two mitotic steps in which a role of Rab6 and Rab11 has been previously documented. We propose that R6IP1 may couple Rab6 and Rab11 function throughout the cell cycle. PMID- 17725554 TI - Diversity and persistence of arbuscular mycorrhizas in a low-Arctic meadow habitat. AB - Little is known about the ecology and diversity of arbuscular mycorrhizal (AM) fungi in Arctic ecosystems. Here, the diversity and composition of the AM fungal community and its response to host plant community composition were studied in a low-Arctic meadow habitat. The natural vegetation in two low-Arctic meadow sites was manipulated. Plots with natural vegetation, monoculture and no vegetation were established. Seeds of Solidago virgaurea were sown into the plots and the AM fungal community in the seedling roots was analysed using the terminal restriction fragment length polymorphism (T-RFLP) method. The vegetation manipulation treatments affected the community composition but not the diversity of AM fungi found in S. virgaurea roots. The diversity of AM fungi was higher in S. virgaurea roots in the site with naturally higher plant species diversity. These results show that AM fungi in low-Arctic meadows are able to survive for a period of 2 yr without a host plant. This ability buffers the AM fungal community against short-term changes in host plant community composition and diversity. PMID- 17725555 TI - Citrate exudation from white lupin induced by phosphorus deficiency differs from that induced by aluminum. AB - Both phosphorus (P) deficiency and aluminum (Al) toxicity induce root exudation of carboxylates, but the relationship between these two effects is not fully understood. Here, carboxylate exudation induced by Al in Lupinus albus (white lupin) was characterized and compared with that induced by P deficiency. Aluminum treatments were applied to whole root systems or selected root zones of plants with limited (1 microM) or sufficient (50 microM) P supply. Aluminum stimulated citrate efflux after 1-2 h; this response was not mimicked by a similar trivalent cation, La(3+). P deficiency triggered citrate release from mature cluster roots, whereas Al stimulated citrate exudation from the 5- to 10-mm subapical root zones of lateral roots and from mature and senescent cluster roots. Al-induced citrate exudation was inhibited by P limitation at the seedling stage, but was stimulated at later growth stages. Citrate exudation was sensitive to anion-channel blockers. Al treatments did not affect primary root elongation, but inhibited the elongation of lateral roots. The data demonstrate differential patterns of citrate exudation in L. albus, depending on root zone, developmental stage, P nutritional status and Al stress. These findings are discussed in terms of possible functions and underlying mechanisms. PMID- 17725556 TI - Mating patterns and pollen dispersal in a heterodichogamous tree, Juglans mandshurica (Juglandaceae). AB - Mating patterns in heterodichogamous species are generally considered to be disassortative between flowering morphs, but this hypothesis has hitherto not been vigorously tested. Here, mating patterns and pollen dispersal were studied in Juglans mandshurica, a heterodichogamous wind-pollinated species that is widely distributed in northern and north-eastern China. Paternity analyses carried out on 11 microsatellite loci were used to estimate morph-specific rates of outcrossing and disassortative mating. Pollen dispersal and genetic structure were also investigated in the population under study. The mating pattern of J. mandshurica was highly outcrossing and disassortative. Pairwise values of intramorph relatedness were much higher than those of intermorph relatedness, and a low level of biparental inbreeding was detected. There was no significant difference in outcrossing and disassortative mating rates between the two morphs. The effective pollen dispersal distribution showed an excess of near-neighbor matings, and most offspring of individual trees were sired by one or two nearby trees. These results corroborate the previous suggestion that mating in heterodichogamous plant species is mainly disassortative between morphs, which not only prevents selfing but also effectively reduces intramorph inbreeding. PMID- 17725557 TI - Stable hydrogen isotope ratios of lignin methoxyl groups as a paleoclimate proxy and constraint of the geographical origin of wood. AB - Stable isotope ratios of organic compounds are valuable tools for determining the geographical origin, identity, authenticity or history of samples from a vast range of sources such as sediments, plants and animals, including humans. Hydrogen isotope ratios (delta(2)H values) of methoxyl groups in lignin from wood of trees grown in different geographical areas were measured using compound specific pyrolysis isotope ratio mass spectrometry analysis. Lignin methoxyl groups were depleted in (2)H relative to both meteoric water and whole wood. A high correlation (r(2) = 0.91) was observed between the delta(2)H values of the methoxyl groups and meteoric water, with a relatively uniform fractionation of 216 +/- 19 per thousand recorded with respect to meteoric water over a range of delta(2)H values from -110 in northern Norway to +20 per thousand in Yemen. Thus, woods from northern latitudes can be clearly distinguished from those from tropical regions. By contrast, the delta(2)H values of bulk wood were only relatively poorly correlated (r(2) = 0.47) with those of meteoric water. Measurement of the delta(2)H values of lignin methoxyl groups is potentially a powerful tool that could be of use not only in the constraint of the geographical origin of lignified material but also in paleoclimate, food authenticity and forensic investigations. PMID- 17725558 TI - Repression of Clostridium difficile toxin gene expression by CodY. AB - CodY, a global regulator of gene expression in low G + C Gram-positive bacteria, was found to repress toxin gene expression in Clostridium difficile. Inactivation of the codY gene resulted in derepression of all five genes of the C. difficile pathogenicity locus during exponential growth and stationary phase. CodY was found to bind with high affinity to a DNA fragment containing the promoter region of the tcdR gene, which encodes a sigma factor that permits RNA polymerase to recognize promoters of the two major toxin genes as well as its own promoter. CodY also bound, but with low affinity, to the toxin gene promoters, suggesting that the regulation of toxin gene expression by CodY occurs primarily through direct control of tcdR gene expression. Binding of CodY to the tcdR promoter region was enhanced in the presence of GTP and branched-chain amino acids, suggesting a link between nutrient limitation and the expression of C. difficile toxin genes. PMID- 17725560 TI - Role of the Escherichia coli SbmA in the antimicrobial activity of proline-rich peptides. AB - In contrast to many antimicrobial peptides, members of the proline-rich group of antimicrobial peptides inactivate Gram-negative bacteria by a non-lytic mechanism. Several lines of evidence indicate that they are internalized into bacteria and their activity mediated by interaction with unknown cellular components. With the aim of identifying such interactors, we selected mutagenized Escherichia coli clones resistant to the proline-rich Bac7(1-35) peptide and analysed genes responsible for conferring resistance, whose products may thus be involved in the peptide's mode of action. We isolated a number of genomic regions bearing such genes, and one in particular coding for SbmA, an inner membrane protein predicted to be part of an ABC transporter. An E. coli strain carrying a point mutation in sbmA, as well as other sbmA-null mutants, in fact showed resistance to several proline-rich peptides but not to representative membranolytic peptides. Use of fluorescently labelled Bac7(1-35) confirmed that resistance correlated with a decreased ability to internalize the peptide, suggesting that a bacterial protein, SbmA, is necessary for the transport of, and for susceptibility to, proline-rich antimicrobial peptides of eukaryotic origin. PMID- 17725561 TI - Systematic mutagenesis of the thymidine tract of the pyrBI attenuator and its effects on intrinsic transcription termination in Escherichia coli. AB - The pyrBI attenuator of Escherichia coli is an intrinsic transcription terminator composed of DNA with a hyphenated dyad symmetry and an adjacent 8 bp T:A tract (T tract). These elements specify a G+C-rich terminator hairpin followed by a run of eight uridine residues (U-tract) in the RNA transcript. In this study, we examined the effects on in vivo transcription termination of systematic base substitutions in the T/U-tract of the pyrBI attenuator. We found that these substitutions diminished transcription termination efficiency to varying extents, depending on the nature and position of the substitution. In general, substitutions closer to the dyad symmetry/terminator hairpin exhibited the most significant effects. Additionally, we examined the effects on in vivo transcription termination of mutations that insert from 1 to 4 bases between the terminator hairpin and U-tract specified by the pyrBI attenuator. Our results show an inverse relationship between termination efficiency and the number of bases inserted. The effects of the substitution and insertion mutations on termination efficiency at the pyrBI attenuator were also measured in vitro, which corroborated the in vivo results. Our results are discussed in terms of the current models for intrinsic transcription termination and estimating termination efficiencies at intrinsic terminators of other bacteria. PMID- 17725559 TI - Alterations in local chromatin environment are involved in silencing and activation of subtelomeric var genes in Plasmodium falciparum. AB - Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by the var gene family, undergoes antigenic variation and plays an important role in chronic infection and severe malaria. Only a single var gene is transcribed per parasite, and epigenetic control mechanisms are fundamental in this strategy of mutually exclusive transcription. We show that subtelomeric upsB var gene promoters carried on episomes are silenced by default, and that promoter activation is sufficient to silence all other family members. However, they are active by default when placed downstream of a second active var promoter, underscoring the significance of local chromatin environment and nuclear compartmentalization in var promoter regulation. Native chromatin covering the SPE2-repeat array in upsB promoters is resistant to nuclease digestion, and insertion of these regulatory elements into a heterologous promoter causes local alterations in nucleosomal organization and promoter repression. Our findings suggest a common logic underlying the transcriptional control of all var genes, and have important implications for our understanding of the epigenetic processes involved in the regulation of this major virulence gene family. PMID- 17725562 TI - Identification of the genes directly controlled by the response regulator CiaR in Streptococcus pneumoniae: five out of 15 promoters drive expression of small non coding RNAs. AB - The two-component regulatory system CiaRH of Streptococcus pneumoniae has been implicated in beta-lactam resistance, maintenance of cell integrity, competence and virulence, but the genes that are regulated directly by the system have not been defined. Using transcriptional mapping, in vitro CiaR binding, and in vivo analysis of CiaR-mediated regulation, 15 promoters were identified to be directly controlled by the response regulator CiaR. A direct repeat, TTTAAG-N5-TTTAAG, was found to be essential for CiaR binding and regulation. It is present, either completely or with subtle changes, in all promoter regions. Fourteen promoters of the regulon are activated by CiaR, and one was found to be controlled negatively. The genes that are transcribed from these promoters included ciaRH, loci that are predicted to be involved in the modification of teichoic acids (lic), in sugar metabolism (mal, man), stress response (htrA), chromosome segregation (parB), protease maturation (ppmA) and unknown functions. Remarkably, the five strongest promoters of the CiaR regulon drive expression of small RNAs. These small RNAs, designated csRNAs for cia-dependent small RNAs, are non-coding, between 87 and 151 nt in size, and show a high degree of similarity to each other. The analysis of deletion mutants in the csRNA genes revealed that csRNA4 and csRNA5 affect stationary-phase autolysis. The identification of five small non-coding regulatory RNAs opens new perspectives to approach the physiological role of the CiaRH two-component regulatory system. PMID- 17725563 TI - Escherichia coli phage-shock protein A (PspA) binds to membrane phospholipids and repairs proton leakage of the damaged membranes. AB - Escherichia coli phage-shock protein A (PspA), a 25.3 kDa peripheral membrane protein, is induced under the membrane stress conditions and is assumed to help maintain membrane potential. Here, we report that purified PspA, existing as a large oligomer, is really able to suppress proton leakage of the membranes. This was demonstrated for membrane vesicles prepared from the PspA-lacking E. coli mutants, and for membrane vesicles damaged by ethanol and Triton X-100 prepared from the mutant and the wild-type cells. PspA also suppressed proton leakage of damaged liposomes made from E. coli total lipids. Furthermore, we found that PspA bound preferentially to liposomes containing phosphatidylserine and phosphatidylglycerol. All these effects were not observed for monomer PspA that was prepared by refolding of urea-denatured PspA. These results indicate that oligomers of PspA bind to membrane phospholipids and suppress proton leakage. PMID- 17725564 TI - The MarR-type repressor MhqR (YkvE) regulates multiple dioxygenases/glyoxalases and an azoreductase which confer resistance to 2-methylhydroquinone and catechol in Bacillus subtilis. AB - Catechol and 2-methylhydroquinone (2-MHQ) cause the induction of the thiol specific stress response and four dioxygenases/glyoxalases in Bacillus subtilis. Using transcription factor arrays, the MarR-type regulator YkvE was identified as a repressor of the dioxygenase/glyoxalase-encoding mhqE gene. Transcriptional and proteome analyses of the DeltaykvE mutant revealed the upregulation of ykcA (mhqA), ydfNOP (mhqNOP), yodED (mhqED) and yvaB (azoR2) encoding multiple dioxygenases/glyoxalases, oxidoreductases and an azoreductase. Primer extension experiments identified sigma(A)-type promoter sequences upstream of mhqA, mhqNOP, mhqED and azoR2 from which transcription is elevated after thiol stress. DNase I footprinting analysis showed that YkvE protects a primary imperfect inverted repeat with the consensus sequence of tATCTcgaAtTCgAGATaaaa in the azoR2, mhqE and mhqN promoter regions. Analysis of mhqE-promoter-bgaB fusions confirmed the significance of YkvE binding to this operator in vivo. Adjacent secondary repeats were protected by YkvE in the azoR2 and mhqN promoter regions consistent with multiple DNA-protein binding complexes. DNA-binding activity of YkvE was not directly affected by thiol-reactive compounds in vitro. Mutational analyses showed that MhqA, MhqO and AzoR2 confer resistance to 2-MHQ. Moreover, the DeltaykvE mutant displayed a 2-MHQ and catechol resistant phenotype. YkvE was renamed as MhqR controlling a 2-MHQ and catechol-resistance regulon of B. subtilis. PMID- 17725565 TI - Substrate induction of siderophore transport in Bacillus subtilis mediated by a novel one-component regulator. AB - When iron is scarce, Bacillus subtilis expresses genes involved in the synthesis and uptake of the siderophore bacillibactin (BB) and uptake systems to pirate other microbial siderophores. Here, we demonstrate that transcriptional induction of the feuABCybbA operon, encoding the Fe-BB uptake system, is mediated by Btr (formerly YbbB), which is encoded by the immediately upstream gene. Btr contains an AraC-type DNA binding domain fused to a substrate binding protein (SBP) domain related to FeuA, the SBP for Fe-BB uptake. When cells are iron-limited, the Fur mediated repression of btr is relieved and Btr binds to a conserved direct repeat sequence adjacent to feuA to activate transcription. If BB is present, Btr further activates feuA expression. Btr binds with high affinity to both apo-BB and Fe-BB, and the resulting complex displays a significantly increased efficacy as a transcriptional activator relative to Btr alone. Btr can also activate transcription in response to the structurally similar siderophore enterobactin, although genetic analyses indicate that the two siderophores make distinct interactions with the Btr substrate binding domain. Thus, the FeuABC transporter is optimally expressed under conditions of iron starvation, when Fur-mediated repression is relieved, and in the presence of its cognate substrate. PMID- 17725566 TI - Assimilation of NAD(+) precursors in Candida glabrata. AB - The yeast pathogen Candida glabrata is a nicotinamide adenine dinucleotide (NAD(+)) auxotroph and its growth depends on the environmental supply of vitamin precursors of NAD(+). C. glabrata salvage pathways defined in this article allow NAD(+) to be synthesized from three compounds - nicotinic acid (NA), nicotinamide (NAM) and nicotinamide riboside (NR). NA is salvaged through a functional Preiss Handler pathway. NAM is first converted to NA by nicotinamidase and then salvaged by the Preiss-Handler pathway. Salvage of NR in C. glabrata occurs via two routes. The first, in which NR is phosphorylated by the NR kinase Nrk1, is independent of the Preiss-Handler pathway. The second is a novel pathway in which NR is degraded by the nucleosidases Pnp1 and Urh1, with a minor role for Meu1, and ultimately converted to NAD(+) via the nicotinamidase Pnc1 and the Preiss Handler pathway. Using C. glabrata mutants whose growth depends exclusively on the external NA or NR supply, we also show that C. glabrata utilizes NR and to a lesser extent NA as NAD(+) sources during disseminated infection. PMID- 17725567 TI - Genetics and evolution of weedy Helianthus annuus populations: adaptation of an agricultural weed. AB - Agricultural weeds are a major cost to economies throughout the world, and have evolved from numerous plant species in many different plant families. Despite their ubiquity, we do not yet know how easily or often weeds evolve from their wild ancestors or the kinds of genes underlying their evolution. Here we report on the evolution of weedy populations of the common sunflower Helianthus annuus. We analysed 106 microsatellites in 48 individuals from each of six wild and four weed populations of the species. The statistical tests lnRV and lnRH were used to test for significant reductions in genetic variability at each locus in weedy populations compared to nearby wild populations. Between 1% and 6% of genes were significant outliers with reduced variation in weedy populations, implying that a small but not insignificant fraction of the genome may be under selection and involved in adaptation of weedy sunflowers. However, there did not appear to be a substantial reduction in variation across the genome, suggesting that effective population sizes have remained very large during the recent evolution of these weedy populations. Additional analyses showed that weedy populations are more closely related to nearby wild populations than to each other, implying that weediness likely evolved multiple times within the species, although a single origin followed by gene flow with local populations cannot be ruled out. Together, our results point to the relative ease with which weedy forms of this species can evolve and persist despite the potentially high levels of geneflow with nearby wild populations. PMID- 17725569 TI - Molecular signatures of Pleistocene sea-level changes that affected connectivity among freshwater shrimp in Indo-Australian waters. AB - A major paradigm in evolutionary biology asserts that global climate change during the Pleistocene often led to rapid and extensive diversification in numerous taxa. Recent phylogenetic data suggest that past climatic oscillations may have promoted long-distance marine dispersal in some freshwater crustacea from the Indo-Australian Archipelago (IAA). Whether this pattern is common, and whether similar processes are acting on diversification below the species level is unknown. We used nuclear and mitochondrial molecular variation in a freshwater dependent decapod crustacean (Macrobrachium rosenbergii), sampled widely from the IAA, to assess the impact of Pleistocene sea-level changes on lineage diversification in this species. Fitting of an isolation with migration model enabled us to reject ongoing migration among lineages, and results indicate that isolation among both mainland-mainland and mainland-island lineages arose during the mid-Pleistocene. Our data suggest a scenario of widespread marine dispersal during Pleistocene glacial maxima (in support of the 'Pleistocene marine dispersal hypothesis') when sea levels were low, and geographical distances between fresh watersheds were greatly reduced, followed by increased isolation as sea levels subsequently rose. PMID- 17725570 TI - The Leptynia hispanica species complex (Insecta Phasmida): polyploidy, parthenogenesis, hybridization and more. AB - The Leptynia hispanica stick insect species complex includes bisexuals, triploid and tetraploid parthenogenetic populations, suggesting that polyploidy has played a central role in the evolution of this complex. An analysis of karyotype, mitochondrial DNA (cox2) and nuclear DNA (ef1-alpha) markers was carried out to clarify phylogenetic relationships and microevolutionary/phylogeographical patterns of the L. hispanica complex. Our analyses suggested a subdivision of bisexual populations into four groups, tentatively proposed as incipient species. Moreover, triploids and tetraploids showed two independent origins, the latter being more ancient than the former. From ef1-alpha analysis, triploids showed hybrid constitution, while the hybrid constitution of tetraploids is likely, but more data are needed. We suggest that L. hispanica is a case of 'geographical parthenogenesis' with parthenogenetic strains colonizing large peripheral ranges, and bisexuals confined to glacial refuge areas. Moreover, the age, wide distribution and competitive advantage of polyploids over diploids, demonstrate their significance in the evolution of the L. hispanica species complex. PMID- 17725571 TI - The California Hotspots Project: identifying regions of rapid diversification of mammals. AB - The high rate of anthropogenic impact on natural systems mandates protection of the evolutionary processes that generate and sustain biological diversity. Environmental drivers of diversification include spatial heterogeneity of abiotic and biotic agents of divergent selection, features that suppress gene flow, and climatic or geological processes that open new niche space. To explore how well such proxies perform as surrogates for conservation planning, we need first to map areas with rapid diversification -'evolutionary hotspots'. Here we combine estimates of range size and divergence time to map spatial patterns of neo endemism for mammals of California, a global biodiversity hotspot. Neo-endemism is explored at two scales: (i) endemic species, weighted by the inverse of range size and mtDNA sequence divergence from sisters; and (ii) as a surrogate for spatial patterns of phenotypic divergence, endemic subspecies, again using inverse-weighting of range size. The species-level analysis revealed foci of narrowly endemic, young taxa in the central Sierra Nevada, northern and central coast, and Tehachapi and Peninsular Ranges. The subspecies endemism-richness analysis supported the last four areas as hotspots for diversification, but also highlighted additional coastal areas (Monterey to north of San Francisco Bay) and the Inyo Valley to the east. We suggest these hotspots reflect the major processes shaping mammal neo-endemism: steep environmental gradients, biotic admixture areas, and areas with recent geological/climate change. Anthropogenic changes to both environment and land use will have direct impacts on regions of rapid divergence. However, despite widespread changes to land cover in California, the majority of the hotspots identified here occur in areas with relatively intact ecological landscapes. The geographical scope of conserving evolutionary process is beyond the scale of any single agency or nongovernmental organization. Choosing which land to closely protect and/or purchase will always require close coordination between agencies. PMID- 17725568 TI - Recombination, balancing selection and adaptive evolution in the aflatoxin gene cluster of Aspergillus parasiticus. AB - Aflatoxins are toxic and carcinogenic polyketides produced by several Aspergillus species that are known to contaminate agricultural commodities, posing a serious threat to animal and human health. Aflatoxin (AF) biosynthesis is almost fully characterized and involves the coordinated expression of approximately 25 genes clustered in a 70-kb DNA region. Aspergillus parasiticus is an economically important and common agent of AF contamination. Naturally occurring nonaflatoxigenic strains of A. parasiticus are rarely found and generally produce O-methylsterigmatocystin (OMST), the immediate precursor of AF. To elucidate the evolutionary forces acting to retain AF and OMST pathway extrolites (chemotypes), we sequenced 21 intergenic regions spanning the entire cluster in 24 A. parasiticus isolates chosen to represent the genetic diversity within a single Georgia field population. Linkage disequilibrium analyses revealed five distinct recombination blocks in the A. parasiticus cluster. Phylogenetic network analyses showed a history of recombination between chemotype-specific haplotypes, as well as evidence of contemporary recombination. We performed coalescent simulations of variation in recombination blocks and found an approximately twofold deeper coalescence for cluster genealogies compared to noncluster genealogies, our internal standard of neutral evolution. Significantly deeper cluster genealogies are indicative of balancing selection in the AF cluster of A. parasiticus and are further corroborated by the existence of trans-species polymorphisms and common haplotypes in the cluster for several closely related species. Estimates of Ka/Ks for representative cluster genes provide evidence of selection for OMST and AF chemotypes, and indicate a possible role of chemotypes in ecological adaptation and speciation. PMID- 17725572 TI - Bipolar gene flow in deep-sea benthic foraminifera. AB - Despite its often featureless appearance, the deep-ocean floor includes some of the most diverse habitats on Earth. However, the accurate assessment of global deep-sea diversity is impeded by a paucity of data on the geographical ranges of bottom-dwelling species, particularly at the genetic level. Here, we present molecular evidence for exceptionally wide distribution of benthic foraminifera, which constitute the major part of deep-sea meiofauna. Our analyses of nuclear ribosomal RNA genes revealed high genetic similarity between Arctic and Antarctic populations of three common deep-sea foraminiferal species (Epistominella exigua, Cibicides wuellerstorfi and Oridorsalis umbonatus), separated by distances of up to 17, 000 km. Our results contrast with the substantial level of cryptic diversity usually revealed by molecular studies, of shallow-water benthic and planktonic marine organisms. The very broad ranges of the deep-sea foraminifera that we examined support the hypothesis of global distribution of small eukaryotes and suggest that deep-sea biodiversity may be more modest at global scales than present estimates suggest. PMID- 17725573 TI - Macoma balthica in the White and Barents Seas: properties of a widespread marine hybrid swarm (Mollusca: Bivalvia). AB - A main molecular subdivision in the circumpolar Macoma balthica complex has been described between Atlantic and Pacific taxa. In NE Europe, the clams of the White and Barents Seas, however, show deviant genetic structures. Using allozyme and mitochondrial DNA data, we explore the hypothesis that these deviations result from hybridization between an Atlantic (M. b. rubra) and an invading Pacific (M. b. balthica) lineage. A practically pure Atlantic Macoma extends from France north to the Varanger Peninsula (NE Norway), whereas populations farther east have genetic compositions intermediate between true Atlantic and true Pacific. Admixture estimates range from 32 to 90% Pacific contribution, with a notable deviation in a nearly pure Atlantic outpost in the Mezen Bay (NE White Sea). The pattern of variation is not one of a simple collinear mixing however. Different characters exhibit different degrees of introgression, and the relative introgression varies regionally. Yet, there are practically no interlocus genotypic disequilibria between the diverged loci, which brings out the White Sea Barents Sea M. balthica as the best-documented marine animal hybrid swarms so far, arisen through amalgamation of genomes previously isolated since pre Pleistocene times. On top of the main admixture pattern, strong geographical structuring is also seen in characters unrelated to the principal systematic distinction. The persistence of the regional patterns indicates restricted gene flow at the present time, despite the high dispersal potential of the species. The causes of this structuring could be in a complex history of colonization events and features of local hydrography enhancing isolation and divergence of populations. PMID- 17725574 TI - The recent spread of a vertically transmitted virus through populations of Drosophila melanogaster. AB - The sigma virus is a vertically transmitted pathogen that commonly infects natural populations of Drosophila melanogaster. This virus is the only known host specific pathogen of D. melanogaster, and so offers a unique opportunity to study the genetics of Drosophila-viral interactions in a natural system. To elucidate the population genetic processes that operate in sigma virus populations, we collected D. melanogaster from 10 populations across three continents. We found that the sigma virus had a prevalence of 0-15% in these populations. Compared to other RNA viruses, we found that levels of viral genetic diversity are very low across Europe and North America. Based on laboratory measurements of the viral substitution rate, we estimate that most European and North American viral isolates shared a common ancestor approximately 200 years ago. We suggest two explanations for this: the first is that D. melanogaster has recently acquired the sigma virus; the second is that a single viral type has recently swept through D. melanogaster populations. Furthermore, in contrast to Drosophila populations, we find that the sigma viral populations are highly structured. This is surprising for a vertically transmitted pathogen that has a similar migration rate to its host. We suggest that the low structure in the viral populations can be explained by the smaller effective population size of the virus. PMID- 17725576 TI - Experimental studies of evolution in guppies: a model for understanding the evolutionary consequences of predator removal in natural communities. AB - Guppies (Poecilia reticulata) in Trinidadian streams are found with a diversity of predators in the lower reaches of streams, but few predators in the headwaters. These differences have caused the adaptive evolution of guppy behaviour, morphology, male colouration and life history. Waterfalls often serve as barriers to the upstream distribution of predators and/or guppies. Such discontinuities make it possible to treat streams like giant test tubes by introducing guppies or predators to small segments of streams from which they were previously excluded. Such experiments enable us to document how fast evolution can occur and the fine spatial scales over which adaptation is possible. They also demonstrate that the role predators play in structuring this ecosystem resembles many others studied from a more purely ecological perspective; in these streams, as elsewhere, predators depress the numbers of individuals in prey species which in turn reduces the effects of the prey species on other trophic levels and hence the structure of the ecosystem. A focus on predators is important in conservation biology because predators are often the organisms that are most susceptible to local extinction. Their selective loss occurs because large predators have been deliberately exterminated and/or are more susceptible to environmental disturbances. Furthermore, we will argue that predator re-introductions might be destabilizing if, in the absence of predators, their prey have evolved in a fashion that makes them highly susceptible to predation, even after time intervals as short as 50-100 years. A better understanding of the evolutionary impacts of top predators will be critical goal for the policy and practice of large carnivore restoration in the future. PMID- 17725575 TI - Differentiation of tundra/taiga and boreal coniferous forest wolves: genetics, coat colour and association with migratory caribou. AB - The grey wolf has one of the largest historic distributions of any terrestrial mammal and can disperse over great distances across imposing topographic barriers. As a result, geographical distance and physical obstacles to dispersal may not be consequential factors in the evolutionary divergence of wolf populations. However, recent studies suggest ecological features can constrain gene flow. We tested whether wolf-prey associations in uninterrupted tundra and forested regions of Canada explained differences in migratory behaviour, genetics, and coat colour of wolves. Satellite-telemetry data demonstrated that tundra wolves (n = 19) migrate annually with caribou (n = 19) from denning areas in the tundra to wintering areas south of the treeline. In contrast, nearby boreal coniferous forest wolves are territorial and associated year round with resident prey. Spatially explicit analysis of 14 autosomal microsatellite loci (n = 404 individuals) found two genetic clusters corresponding to tundra vs. boreal coniferous forest wolves. A sex bias in gene flow was inferred based on higher levels of mtDNA divergence (F(ST) = 0.282, 0.028 and 0.033; P < 0.0001 for mitochondrial, nuclear autosomal and Y-chromosome markers, respectively). Phenotypic differentiation was substantial as 93% of wolves from tundra populations exhibited light colouration whereas only 38% of boreal coniferous forest wolves did (chi(2) = 64.52, P < 0.0001). The sharp boundary representing this discontinuity was the southern limit of the caribou migration. These findings show that substantial genetic and phenotypic differentiation in highly mobile mammals can be caused by prey-habitat specialization rather than distance or topographic barriers. The presence of a distinct wolf ecotype in the tundra of North America highlights the need to preserve migratory populations. PMID- 17725578 TI - Akt phosphorylation is required for heat acclimation-induced neuroprotection. AB - Long-term heat exposure, known as heat acclimation (HA; 30 days at 34 +/- 1 degrees C) is neuroprotective against traumatic brain injury. Acclimated mice were previously found to display improved functional recovery as well as an increase in the levels of the specific erythropoietin receptor. As the activation of this receptor is known to facilitate functional recovery on one hand and the phosphorylation and activation of Akt, an intracellular kinase which regulates anti-apoptotic pathways on the other, in this study we investigated whether HA affects Akt phosphorylation prior to and following injury and whether this step is required for development of HA-induced neuroprotection. Akt phosphorylation was blocked using Triciribine (TCN), a compound shown to block the phosphorylation process without affecting upstream effectors of this kinase, and several post-injury functional end-point measures were subsequently evaluated. Acclimation led to a post-injury increase in the levels of phosphorylated Akt, resulting in higher levels when compared with normothermic controls at 4 h post injury (63.6 +/- 5.2% and 42.7 +/- 3.7%, respectively, p 99%). We use the NHI database to investigate the epidemiological features of BA and compare Taiwan's annual BA incidence with that of other countries. RESULTS: We identified 327 new BA cases during the period from 1996 to 2003. The overall incidence of BA was 1.46 cases per 10 000 live births (0.89-1.90 per 10 000). The estimation was 1.32-1.65 per 10 000 after adjustment for the misdiagnosis rate. The peak incidence occurred in 2002 (1.90 per 10 000), accompanying Taiwan's dengue fever epidemic in 2002. The 5-year overall survival rate during 1999-2003 was higher than that during 1996-1998 (74.8% vs 61.1%, P = 0.014). CONCLUSION: Taiwan has the second-highest incidence of BA reported in world literature. Viral infection outbreaks remain a potential candidate as a cause of BA. The management of BA has been improving, with a better 5-year overall survival rate. PMID- 17725593 TI - Helicobacter pylori infection and allergic diseases: epidemiological study in Japanese university students. AB - BACKGROUND AND AIM: A negative association between Helicobacter pylori infection and allergic diseases has not been consistent. The aim of this study was to examine the association between allergic diseases and H. pylori infection in Japan. METHODS: Newly enrolled university students completed health survey questionnaires regarding general health and the presence of allergic diseases. Helicobacter pylori status was determined by the presence of serum H. pylori IgG and the presence of allergic manifestations was confirmed by interview. RESULTS: A total of 1953 students had a routine health survey; H. pylori status was determined in 777 including 369 with allergic diseases and 408 controls. The reported frequency of allergic rhinoconjunctivitis, atopic dermatitis, urticaria, bronchial asthma and mixed diseases was 29.0%, 11.1%, 2.0%, 0.9% and 5.0%, respectively. Helicobacter pylori infection was diagnosed less frequently in the allergic group compared with controls (11.4% vs 17.6%, P = 0.015). Helicobacter pylori infection was less frequent in men with allergic diseases (OR 0.49, 95% CI 0.27-0.89). CONCLUSION: Allergic diseases are frequent in young Japanese adults and are negatively associated with H. pylori infection especially in men. PMID- 17725592 TI - Clinical and genetic factors associated with sacroiliitis in Crohn's disease. AB - BACKGROUND AND AIM: Radiographic sacroiliitis (SI), often asymptomatic, is considered the most frequent extra-intestinal manifestation (EIM) of Crohn's disease (CD). Data on the association of SI with other clinical features of CD are limited. Association of SI with CARD15 polymorphisms has recently been suggested. In a multicenter study, we investigated the association of SI in CD patients with clinical phenotypes, other EIM and CARD15 polymorphisms. METHODS: Radiographs of the sacroiliac joints were taken in 251 CD patients from three Belgian university hospitals and scored by two blinded rheumatologists. Clinical features were obtained from medical records. Forty-three percent of patients carried at least one CARD15 polymorphism. RESULTS: Sacroiliitis, defined as the presence of at least grade 2 unilateral changes, was diagnosed in 65 of the 244 scorable radiographs (27%). Only 16 of these patients were previously diagnosed with ankylosing spondylitis (AS). HLA-B27 positivity was observed in 53% of patients with AS and 7% of patients with radiographic SI. In univariate and multivariate analysis, associations between the presence of SI and peripheral arthritis (P = 0.005) and between AS and uveitis (P = 0.005) were found. No associations with other recorded clinical features or with CARD15 polymorphisms were observed. CONCLUSION: We confirm the high prevalence of radiographic sacroiliitis in a multicenter CD cohort. Uveitis is only associated with AS whereas all patients with SI are more prone to develop peripheral arthritis during their disease course, suggesting similar pathogenetic mechanisms in the development of these EIM. The previously reported association between SI and CARD15 polymorphisms was not confirmed. PMID- 17725594 TI - Plasma concentration of rabeprazole after 8-week administration in gastroesophageal reflux disease patients and intragastric pH elevation. AB - BACKGROUND AND AIM: The plasma concentration of rabeprazole in patients treated for gastroesophageal reflux disease (GERD) has not been reported, although the concentration in healthy volunteers has been reported previously. Here, CYP2C19 genotype effects of rabeprazole on the area under the plasma concentration-time curve (AUC) and the pH elevation were studied in GERD patients. METHODS: Rabeprazole 10 mg/day was administrated for 8 weeks. AUC of rabeprazole in 18 Helicobacter pylori-negative GERD subjects (five CYP2C19 homozygous extensive metabolizers [homEM], eight heterozygous extensive metabolizers [hetEM] and five poor metabolizers [PM]) were determined after the final medication. Intragastric pH was recorded for 24 h at baseline and after the final medication. RESULTS: The AUC in the PM group (957 ng x h/mL) was significantly higher than those of homEM (375 ng x h/mL) and hetEM (542 ng x h/mL) groups. Median 24-h pH curves, median 24-h pH values and 24-h and nocturnal pH > 4 and pH > 3 holding times did not significantly differ among these groups. Disappearance of erosive lesions was observed after the treatment in all subjects with grade A, B or C at baseline irrespective of CYP2C19 genotypes. CONCLUSION: The AUC of rabeprazole depended on the CYP2C19 genotypes in Japanese GERD patients; however, the intragastric pH elevation was independent of CYP2C19 genotypes, which is consistent with the CYP2C19 genotype-independent healing efficacy of erosive lesions by rabeprazole. The present low AUC values indicated that abnormal accumulative effects on AUC did not occur during the period of the 8-week administration of rabeprazole. PMID- 17725595 TI - Clinical features of Japanese patients with colonic angiodysplasia. AB - BACKGROUND AND AIM: With improvements in endoscopic resolution, angiodysplasia (AGD) has become an increasingly recognized disorder. The aim of this study was to describe the clinical features of Japanese patients with colonic AGD and compare them to the clinical features of Western patients. METHODS: Retrospective analyses were performed in all patients who had undergone colonoscopical examination from March 2003 to October 2005 at the Kyoto University Hospital. Four independent literature searches were performed to document the characteristics of colonic AGD in Western countries. The characteristics of 41 Japanese patients diagnosed as having colonic AGD were compared with those of Western patients. RESULTS: The incidence of colonic AGD increased with age, and the most prevalent underlying disease in patients with colonic AGD was cardiovascular disease (56.1%). These tendencies were similar in the Japanese and Western data. Colonic AGD in Japanese patients was predominantly located in the left colon (41.7%), whereas in Western patients, it was mainly located in the right colon (54%-81.9%). The percentage of colonic AGD with a size of more than 5 mm or elevated type detected in Japanese patients was significantly higher than that in Western patients. CONCLUSION: The characteristics of Japanese patients with colonic AGD were similar to those of Western patients, except for its localization, size, and type. PMID- 17725596 TI - Visceral obesity as a risk factor for colorectal neoplasm. AB - BACKGROUND AND AIM: Obesity as a risk factor for colorectal neoplasm (CRN) is controversial. In the present study, we evaluated visceral obesity as a risk factor for CRN. METHODS: We prospectively enrolled 200 consecutive, asymptomatic adults (male : female = 133:67, mean age, 50.9 +/- 8.5 years) undergoing both colonoscopy and abdominopelvic computed tomography (CT) scan for routine health evaluations. The presence or absence and the characteristics of CRN were determined during colonoscopy. The amount of visceral adipose tissue (VAT) and subcutaneous adipose tissue was measured by an abdominopelvic CT scan. Body mass index, waist circumference, and percentage of body fat were measured. Blood pressure and other blood markers for assessing the metabolic syndrome were also investigated. RESULTS: Of the 200 patients, 53 (26.5%) had CRN. Old age, smoking, metabolic syndrome, and a high fasting plasma glucose level were associated with an increased risk of CRN. VAT (P < 0.01) and waist circumference (P = 0.01) were significantly higher in those with CRN. A multivariate analysis of the risks of CRN showed an odds ratio of 4.07 (95% confidence interval: 1.01-16.43, P = 0.03) for those with VAT over 136.61 cm(2) relative to those with VAT under 67.23 cm(2). Waist circumference, metabolic syndrome, and fasting plasma glucose levels were not independent risk factors for CRN in the multivariate analysis. CONCLUSION: Increased VAT is an independent risk factor for CRN. Further large scale studies are needed to clarify the causal relationship between VAT and CRN. PMID- 17725597 TI - Role of metallothionein in Helicobacter pylori-positive gastric mucosa with or without early gastric cancer and the effect on its expression after eradication therapy. AB - BACKGROUND AND AIM: Metallothionein (MT) has a proven relationship with various kinds of cancer and reduces tissue damage. Helicobacter pylori (H. pylori) infection is associated with the alteration of gastric epithelial cell cycle events, a condition implicated in the initiation and development of gastric cancer. This study investigates the role of MT in H. pylori-induced gastritis with or without early gastric cancer (ECG) and evaluates the effect on MT expression after eradication therapy. METHODS: Gastric biopsy samples were immunohistochemically examined for MT expression in 36 H. pylori-negative patients without ECG and 98 positive patients with or without ECG. Real time polymerase chain reaction was performed in 14 antral biopsy samples with or without H. pylori. The severity of gastritis was also evaluated according to the updated Sydney System. In 31 successfully eradicated patients, the above assessment was repeated for two consecutive years. RESULTS: MT expression was higher in H. pylori-negative patients than in positive patients (P < 0.01). Moreover, in the corpus it was higher in H. pylori-positive patients without ECG compared to those with ECG (P < 0.05). The MT labeling index had a negative correlation with the severity of gastritis (P < 0.01). A positive correlation was shown between the MT labeling index and apoptosis: proliferation ratio (r = 0.41, P < 0.01). The MT labeling index in H. pylori-positive patients was gradually recovered after eradication (P < 0.05). CONCLUSION: The decrease of MT expression cannot prevent tissue damage in H. pylori-positive gastric mucosa and leads to more severe gastritis. This phenomenon may be attributed to gastric carcinogenesis. H. pylori eradication increases MT expression and may reduce the risk of ECG. PMID- 17725598 TI - Serum YKL-40 as a marker of disease activity and stricture formation in patients with Crohn's disease. AB - BACKGROUND AND AIM: YKL-40 is secreted by macrophages and neutrophils and is a growth factor for vascular endothelial cells and fibroblasts. Elevated serum levels of YKL-40 have been reported in patients with various inflammatory conditions and ongoing fibrosis. The aim of this study was to investigate the relationship between serum concentrations of YKL-40 and disease activity, acute phase reactants, and the presence of strictures in patients with Crohn's disease (CD). METHODS: We studied the serum concentrations of YKL-40 in 41 patients with CD, in which 12 had an endoscopically- or radiologically-proven stricture formation. Forty-six age- and sex-matched healthy volunteers served as controls and a multivariate regression analysis was performed to find out the independent predictors of intestinal strictures and clinical activity. RESULTS: The serum YKL 40 concentrations in the patients were significantly higher than that in the healthy controls (105.69 +/- 88.08 ng/mL [range 20.23-333.57]vs 44.92 +/- 24.89 ng/mL [range 18.31-113.43], P = 0.000) and patients with a stricture formation had significantly higher YKL-40 levels than those without strictures (167.50 +/- 119.30 ng/mL [range 23.62-333.57]vs 80.12 +/- 56.38 ng/mL [range 20.23-259.19], P = 0.003). Significant correlations were noted between YKL-40 levels and clinical activity (r = 0.681; P = 0.000) and the presence of intestinal strictures (r = 0.457; P = 0.003). The multivariate regression analysis found the serum YKL-40 levels to be an independent predictor of intestinal strictures (P = 0.001) and clinical activity (P = 0.001). CONCLUSION: Patients with CD, particularly those with a stricture formation, have significantly higher levels of YKL-40. YKL-40 seems to be a useful marker of disease activity as well as stricture formation in patients with CD. PMID- 17725599 TI - Risk factors for local and distant recurrence of hepatocellular carcinomas after local ablation therapies. AB - BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) recurs frequently after local ablation therapies. Recurrence following the therapies may be of two types: local recurrence and distant recurrence. The aim of the current study is to separately elucidate the predisposing factors for each recurrence. METHODS: Among the 2141 consecutive patients with HCC who were admitted to our institute and affiliated hospital between May 1997 and April 2004, 621 patients who had undergone local ablation therapies as the initial treatment were enrolled. Correlations between the clinical backgrounds of the patients and the type of recurrence were analyzed by the Cox proportional hazard model. RESULTS: A multivariate analysis revealed that tumor size (>30 mm; risk ratio 2.80; 95% confidence interval, 1.77-4.45; P < 0.0001), tumor number (> or =2; 1.74, 1.23-2.47, P = 0.002), and the serum alpha fetoprotein level (>100 ng/mL; (1.62, 1.09-2.41, P = 0.014), which were classified as "tumor factors", were significant predisposing factors for the local recurrence of HCC. In contrast, a low platelet count (<100,000/microL; 1.34, 1.04-1.74, P = 0.03) and the presence of ascites (1.73, 1.16-2.57, P = 0.008), which were classified as "background factors", as well as tumor size (1.83, 1.11-3.01, P = 0.02) and tumor number (2.23, 1.72-3.00, P < 0.0001) were predisposing factors for distant recurrence. CONCLUSION: The predisposing factors for local and distant recurrence of HCC differ and different precautions must be observed to prevent recurrence, depending on the HCC status and background liver functions. PMID- 17725600 TI - Increased esophageal mucosal/submucosal blood flow in patients with gastroesophageal reflux disease: normalization by treatment with a proton pump inhibitor. AB - BACKGROUND AND AIM: Mucosal injury caused by gastroesophageal reflux may result in changes in esophageal mucosal blood flow. Little is known about esophageal mucosal blood flow in patients with gastroesophageal reflux disease (GERD). Here we examined esophageal mucosal blood flow and the effects of treatment in patients with GERD. METHODS: The subjects included 41 cases (21 males and 20 females, mean age 64.2 years) in whom endoscopy was warranted in patients complaining of heartburn and/or regurgitation. We also studied six normal control subjects. Patients underwent endoscopy, laser Doppler flow meter measurements, and endoscopic ultrasonography before and after treatment. RESULTS: Esophageal mucosal/submucosal blood flow was increased in patients with GERD compared with the control patients. The thickness of the whole esophageal wall and that of the mucosal and submucosal layers of the esophagus correlated significantly with esophageal mucosal/submucosal blood flow. The increased esophageal mucosal/submucosal blood flow significantly decreased after 4 weeks' treatment with lansoprazole, a proton pump inhibitor. CONCLUSION: Our results indicated that the pathophysiology or underlying mechanisms of GERD includes increased esophageal mucosal/submucosal blood flow, which correlates with the thickness of the esophageal wall, but is reversible and responds to treatment with lansoprazole. This suggests that proton pump inhibitors can effectively treat GERD and promote histological normalization of the mucosa and submucosa in the lower esophagus. PMID- 17725601 TI - Functional hepatic recovery after xenotransplantation of cryopreserved fetal liver cells or soluble cell-factor administration in a cirrhotic rat model: are viable cells necessary? AB - BACKGROUND AND AIM: Chronic liver failure results in the decrease of the number of functioning hepatocytes. It dictates the necessity of using exogenous viable cells or/and agents that can stimulate hepatic regenerative processes. Fetal liver contains both hepatic and hematopoietic stem cells with high proliferative potential, which may replace damaged cells. Also, immature cells produce fetal specific factors which may support the injured liver. Our aim was to test the ability of human fetal liver cells and cell-free fetal-specific factors of non hepatic origin to stimulate recovery processes in an experimental model of carbon tetrachloride-induced cirrhosis in rats. METHODS: Cirrhotic rats were intrasplenically injected with fetal liver cells (1 x 10(7) cells/0.3 mL medium) or cell-free fetal-specific factors (0.3 mL/1 mg protein). Control groups received medium alone. Serum indexes, hepatic functions, and morphology were evaluated for 15 days. RESULT: Human fetal liver cell transplantation was shown to abrogate the mortality of cirrhotic animals, to improve serum markers, and to restore liver mitochondrial function and detoxification. Morphological patterns of liver recovery were observed by histology. In comparison, an injection of fetal-specific factors produced similar functional recovery, whilst a more limited liver regeneration was observed by histology. CONCLUSIONS: The positive effects of fetal liver cell and cell-free fetal-specific factors in experimental cirrhosis may result from the presence of stage-specific factors activating hepatocellular repair. PMID- 17725602 TI - Prevalence of and risk factors for gallbladder polyps detected by ultrasonography among healthy Chinese: analysis of 34 669 cases. AB - BACKGROUND AND AIM: Gallbladder (GB) polyps are tumor or tumor-like projections arising from GB mucosa. Although most polyps are benign, some early GB carcinomas present as polypoid lesions. The diagnosis of GB polyps is relatively easy by ultrasonography. Although numerous studies have investigated GB polyps, few studies have addressed the prevalence of and factors associated with GB polyps for specific ethnic populations. This study analyzes the prevalence and factors associated with GB polyps in a Chinese population who can afford a paid general checkup. METHODS: The prevalence of and risk factors for GB polyps diagnosed by ultrasonography were retrospectively investigated in 34 669 Chinese patients who underwent a general checkup at Chang Gung Memorial Hospital (Taipei, Taiwan) between 2000 and 2003. Demographic, hemogram, serum biochemistry, hepatitis B surface antigen, hepatitis C antibody, and ultrasonography study data was available for all the patients. The correlations between the prevalence of GB polyps and age, sex, body height, body weight, body mass index, hemogram, serum biochemistry, and viral markers were examined for all the patients. RESULTS: Excluding the patients who underwent cholecystectomy, the overall prevalence of GB polyps was 9.5% and highest for middle-aged males. The analyzed risk factors with increased odds ratios (OR) for the development of GB polyps were male sex (OR 0.646, P < 0.0005) and hepatitis B virus surface antigen positivity (OR 1.113, P < 0.0005). Other demographic characteristics and biochemical parameters, including body height, body weight, body mass index, lipid profile, chronic hepatitis C virus infection, and liver function did not correlate with the presence of GB polyps. CONCLUSION: The prevalence of GB polyps among the Chinese in this study is higher than that reported for other populations. Chinese males and other patients with chronic hepatitis B viral infections have a high risk for developing GB polyps. PMID- 17725603 TI - Disturbed colocalization of multidrug resistance protein 2 and radixin in human cholestatic liver diseases. AB - BACKGROUND AND AIM: Endocytic retrieval of multidrug resistance protein 2 (MRP2) is closely associated with cholestasis and may be attributed to the disturbed linking of MRP2 and radixin, a cross-linker between actin filaments and membrane proteins. This study aimed to investigate the role of radixin in the altered localization of MRP2 in various human cholestatic liver diseases. METHODS: Using immunofluorescence microscopy, we investigated the localization and expression of MRP2 and radixin in various cholestatic liver diseases, such as drug-induced liver injury, obstructive jaundice, primary sclerosing cholangitis and autoimmune hepatitis. Changes in localization and expression were analyzed using Scion Image (software). RESULTS: In the icteric drug-induced liver injury, MRP2 was localized outside as well as inside of ZO-1 staining, indicating endocytic retrieval from the canalicular membrane into the pericanalicular compartments of the hepatocytes. The colocalization of MRP2 and radixin observed in the controls was disturbed, and MRP2 fluorescence disappeared in the canaliculi with disrupted radixin staining. Disturbed colocalization of MRP2 and radixin as well as endocytic retrieval of MRP2 was found in the poorly drained obstructive jaundice. When drainage was good, MRP2 was exclusively colocalized with radixin. Similar findings were observed in autoimmune hepatitis and primary sclerosing cholangitis. In the controls, the immunostaining intensity curves for MRP2 and radixin were steeply elevated in the canaliculi. The intensity curves for MRP2 and radixin were broadened in the icteric drug-induced liver injury and poorly drained obstructive jaundice, indicating endocytic retrieval into the hepatocytes. The peak fluorescence intensities for MRP2 and radixin decreased in the icteric liver. CONCLUSION: Disturbed colocalization of MRP2 and radixin was common in various cholestatic liver diseases, which may be associated with endocytic retrieval of MRP2 due to failure in anchoring MRP2 in the canalicular membrane. PMID- 17725605 TI - Induction of MHC class I molecule cell surface expression and epigenetic activation of antigen-processing machinery components in a murine model for human papilloma virus 16-associated tumours. AB - Epigenetic events play an important role in tumour progression and also contribute to escape of the tumour from immune surveillance. In this study, we investigated the up-regulation of major histocompatibility complex (MHC) class I surface expression on tumour cells by epigenetic mechanisms using a murine tumour cell line expressing human E6 and E7 human papilloma virus 16 (HPV16) oncogenes and deficient in MHC class I expression, as a result of impaired antigen presenting machinery (APM). Treatment of the cells with the histone deacetylase inhibitor Trichostatin A, either alone or in combination with the DNA demethylating agent 5-azacytidine, induced surface re-expression of MHC class I molecules. Consequently, the treated cells became susceptible to lysis by specific cytotoxic T lymphocytes. Further analysis revealed that epigenetic induction of MHC class I surface expression was associated with the up-regulation of APM genes [transporter associated with antigen processing 1 (TAP-1), TAP-2, low-molecular-mass protein 2 (LMP-2) and LMP-7]. The results demonstrate that expression of the genes involved in APM are modulated by epigenetic mechanisms and suggest that agents modifying DNA methylation and/or histone acetylation have the potential to change the effectiveness of antitumour immune responses and therapeutically may have an impact on immunological output. PMID- 17725604 TI - Importance of N-linked glycosylation in the functional expression of murine CD1d1. AB - The mouse CD1d1 glycoprotein is specialized in presenting lipid antigens to a novel class of T cells called natural killer T (NKT) cells. CD1d1 is predicted to contain five potential N-linked glycosylation sites (asparagine residues at positions 25, 38, 60, 128, and 183). Glycosylation has been shown to invariably affect the molecular and functional properties of various glycoproteins, and in the current report it was found that a conservative change of the individual endogenous asparagine residues in CD1d1 to glutamine differentially affected its functional expression. Although the maturation rate of the glycosylation mutants was comparable to that of wild type, they differed in their relative levels of surface expression and in their ability to stimulate NKT cells. Mutating all five glycosylation residues resulted in the absence of detectable CD1d1 expression, with a concomitant lack of NKT cell activation. Therefore, these results demonstrate that glycosylation plays a significant role in the functional expression of CD1d1. PMID- 17725606 TI - Impaired expression of indoleamine 2, 3-dioxygenase in monocyte-derived dendritic cells in response to Toll-like receptor-7/8 ligands. AB - The effects of immunostimulatory RNAs (isRNAs) on the expression of immuno suppressive factors are largely unknown. Indoleamine 2,3-dioxygenase (IDO) is a key negative regulator of immune responses and it has been implicated in hampering immunity against tumours. Here we show that the activation of Toll-like receptors (TLR)-7/8 with isRNAs or R848, a specific ligand for TLR7/8, can induce IDO expression in human monocytes, but not in monocyte-derived dendritic cells (moDC). In contrast to TLR7/8 agnosists, treatment of the same moDC with interferon-gamma-induced IDO expression. Treatment of monocytes with 2'-O-methyl uridine-modified isRNAs alone does not induce IDO, but totally abrogated the effects of unmodified isRNAs. Like isRNAs, synthetic viral RNAs and cytomegalovirus (CMV) induced IDO in monocytes, whereas TLR2 ligand lipopeptide Pam3Cys exhibited no effect. Furthermore, IDO positive monocytes suppressed autologous T-cell activation. Collectively, these data indicate for first time that the potency of TLR7/8 signalling pathways to induce IDO expression in monocytes is silenced when the cells are programmed to differentiate into dendritic cells. The immunosuppressive properties of IDO might confer an advantage to CMV-infected monocytes to escape T-cell responses. The findings that 2'-O-methyl modified RNAs can block isRNA-induced IDO expression would facilitate the design of new TLR inhibitors. PMID- 17725607 TI - Defective Toll-like receptor 9-mediated cytokine production in B cells from Bruton's tyrosine kinase-deficient mice. AB - Bruton's tyrosine kinase (Btk), a member of the Tec family of tyrosine kinases, plays an important role in the differentiation and activation of B cells. Mutations affecting Btk cause immunodeficiency in both humans and mice. In this study we set out to investigate the potential role of Btk in Toll-like receptor 9 (TLR9) activation and the production of pro-inflammatory cytokines such as interleukin (IL)-6, tumour necrosis factor (TNF)-alpha and IL-12p40. Our data show that Btk-deficient B cells respond more efficiently to CpG-DNA stimulation, producing significantly higher levels of pro-inflammatory cytokines but lower levels of the inhibitory cytokine IL-10. The quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis presented in this work shows that mRNA production of one of the important new members of the IL-12 family, IL-27, was significantly increased in Btk-deficient B cells after CpG-DNA stimulation. In this study, we demonstrate significant differences in CpG responsiveness between transitional 1 (T1) and T2 B cells for survival and maturation. Furthermore, TLR9 expression, measured both as protein and as mRNA, was increased in Btk-defective cells, especially after TLR9 stimulation. Collectively, these data provide evidence in support of the theory that Btk regulates both TLR9 activation and expression in mouse splenic B cells. PMID- 17725609 TI - Endothelial dysfunction in Turkish patients with non-alcoholic fatty liver disease. AB - BACKGROUND: The components of the metabolic syndrome are closely related with endothelial dysfunction, which is a pathophysiological issue of cardiovascular diseases. Non-alcoholic fatty liver disease (NAFLD) is considered as one of the components of the metabolic syndrome. The aim of this study was to evaluate the endothelial-dependent dilatation (EDD) and endothelial-independent dilatation (EID) of the brachial artery in NAFLD. METHODS: Fifteen non-alcoholic steatohepatitis (NASH), 17 patients with simple steatosis and 16 healthy subjects formed the study group. Non-alcoholic fatty liver disease group was composed of patients admitted to the gastroenterology outpatient clinic because of increased liver enzymes. Endothelial functions of the brachial artery were evaluated by vascular ultrasound. EDD was assessed by establishing reactive hyperaemia, and EID was determined by using sublingual nitrate. RESULTS: No statistical difference for the basal diameter of brachial artery was found between the groups (P = 0.49). The values for EDD and EID were significantly different across all three groups (P < 0.0001 and P < 0.0001, respectively). EDD and EID were significantly lower in NASH compared with simple steatosis (P = 0.01 and P < 0.01, respectively). However, there was no statistical significance for EDD and EID in simple steatosis groups compared with controls (P = 0.58 and P = 0.98, respectively). CONCLUSIONS: Our study showed that patients with NASH had significantly worse endothelial dysfunction compared with patients with simple steatosis and healthy subjects. The treatment strategies with ameliorative effects for endothelial dysfunction might be effective for delaying the development of cardiovascular complications in NAFLD. PMID- 17725608 TI - Surveillance following treatment for colorectal cancer in Australia. Has best practice been adopted by medical oncologists? AB - BACKGROUND: Intensive follow up after surgery for colorectal cancer is associated with a significant survival advantage and is endorsed by expert panels, but are physicians convinced of the benefit? METHODS: A questionnaire was mailed to all members of the Medical Oncology Group of Australia, assessing surveillance practices after completion of adjuvant treatments. RESULTS: Responses were obtained from 141 (55%) medical oncologists of which 121 were considered evaluable. Thirteen per cent (n = 16) routinely did not carry out follow-up investigations. Of those carrying out surveillance, 47% (n = 51) nominated identifying potentially resectable metastatic disease as prime consideration. Many (44%) were motivated by patient reassurance and expectation. Carcinoembryonic antigen levels were commonly monitored 3 monthly in years 1 (77%, n = 85) and 2 (57%, n = 63) and 6 monthly thereafter (67%, n = 74). Eighty per cent (n = 88) carried out computed tomography (CT) surveillance 1 year after surgery, 69% (n = 76) at year 2 and 55% (n = 60) at year 3. Twenty-six per cent (n = 29) continued scanning annually up to 5 years. Inclusion of CT chest was routine for 33% (n = 36) and never carried out by 11% (n = 12). CONCLUSION: A significant minority (13%) of oncologists carry out no follow-up investigations, despite level I evidence of a survival advantage similar to standard adjuvant therapies. Further education and study of physician attitudes and reservations to routine surveillance are required. PMID- 17725610 TI - Insulin-sensitizing antihyperglycaemic medications are associated with better outcome in patients with diabetes undergoing cardiac stress testing. AB - BACKGROUND: There are several treatment modalities available for diabetes; however, the effects of the different medications on coronary artery disease are less understood. The purpose of this study was to evaluate the correlation of insulin-sensitizing therapy with the outcome of stress myocardial perfusion testing and to compare it with conventional therapy. METHODS: Of 417 patients referred to stress testing for evaluation of chest pain, 222 were identified as being treated with conventional therapy only (insulin and insulin secretagogues) and 195 as being treated with insulin sensitizers (metformin and thiazolidinediones (TZD)). Multivariate logistic regression models were used to correct for confounding factors and to determine the independent relation between treatment type and stress-test outcome. RESULTS: Ischaemia, infarction and the composite outcome were less frequent in the insulin-sensitizer group than in the conventional therapy group (odds ratio (OR) = 0.39, P = 0.025; OR = 0.32, P = 0.021 and OR = 0.38, P = 0.009, respectively). The subgroup analysis showed that treatment with metformin (n = 125) compared with conventional therapy was associated with less infarction or the composite outcome of ischaemia and/or ischaemia (OR = 0.18 (95% confidence interval (CI): 0.05-0.66), P = 0.010; OR = 0.34 (95%CI: 0.15-0.80), P = 0.014, respectively). Treatment with TZD (n = 43) was associated with a trend to less frequent ischaemia (OR = 0.18 (95%CI: 0.03 1.01), P = 0.051). CONCLUSION: The addition of insulin-sensitizing medications to the conventional diabetes therapy or their sole use was associated with decreased coronary artery disease or its severity in patients with diabetes as determined by stress myocardial perfusion study. Randomized prospective trials will be necessary to prove this benefit. PMID- 17725611 TI - ITP: a new regulatory issue! PMID- 17725612 TI - Incidence of iris melanoma in western Norway. PMID- 17725613 TI - Visual recovery after vitrectomy for macular hole using 25-gauge instruments. AB - PURPOSE: To determine whether vitrectomy with 25-gauge instruments contributes to better postoperative visual recovery after macular hole (MH) surgery. METHODS: The medical records for 46 consecutive eyes operated for MH by a single surgeon were retrospectively examined. Vitrectomy had been performed with a 25-gauge instrument in 23 eyes (25-G group) and with a 20-gauge instrument in 23 eyes (20 G group). Postoperative visual acuity (VA) in logMAR (logarithm of the minimum angle of resolution) units after 1 week and 1, 3, 6, 9 and 12 months, operating time, and volume of intraocular irrigating fluid were compared between the two groups. RESULTS: Mean preoperative logMAR VA was 0.72 in the 25-G group and 0.68 in the 20-G group (p = 0.282, unpaired t-test). One week after surgery, VA was significantly better in the 25-G group (0.40 +/- 0.34) than in the 20-G group (0.58 +/- 0.30) (p = 0.020). This significant difference was maintained until 9 months after surgery, but was no longer evident at 12 months (p = 0.182). Operating time was significantly shorter in the 25-G group (56 +/- 16 mins) than in the 20-G group (85 +/- 28 mins) (p = 0.003, unpaired t-test). The volume of intraocular irrigating fluid was significantly less in the 25-G group (244 +/- 72 ml) than in the 20-G group (416 +/- 113 ml) (p < 0.0001). CONCLUSIONS: The use of 25-gauge vitrectomy instruments leads to better postoperative visual recovery following surgery for MH during the first 9 months, probably as a result of shorter surgical time and a lower volume of intraocular irrigating fluid. PMID- 17725614 TI - Measurement of health-related quality of life with glaucoma: validation of the Glau-QoL 36-item questionnaire. AB - PURPOSE: To validate a glaucoma-specific health-related quality of life (HRQoL) questionnaire: the Glau-QoL. METHODS: Patients with ocular hypertension (OHT) or glaucoma took part in a cross-sectional psychometric validation study (n = 573) and a separate reproducibility study (n = 244). Patients answered the 36-item Glau-QoL, designed from in-depth patient interviews. RESULTS: The clinical validity of the Glau-QoL was excellent and clearly demonstrated that as disease severity and visual field impairment increased, HRQoL scores for the Psychological Wellbeing, Self-image, Daily Life, Driving, Anxiety and Burden of Treatment domains were negatively affected. Increased age and lower visual acuity were also associated with lower HRQoL scores, although to a lesser extent than the previously mentioned criteria. Worsening of HRQoL domains correlated with the clinical stage of glaucoma: Anxiety and Burden of Treatment scores dropped noticeably when patients were first diagnosed and started treatment, followed by a decrease in scores for Driving, Daily Life, Psychological Wellbeing, and Self image as clinical conditions worsened. Psychometric validation showed acceptable convergent and discriminant validity of the Glau-QoL, and good reproducibility, with intraclass correlation coefficients (ICC) and concordance correlation coefficients (CCC) > or = 0.69. Internal consistency reliability was high (Cronbach's alpha coefficients > 0.70) for the Daily Life, Psychological Wellbeing, Burden of Treatment and Driving domains; acceptable (coefficients of 0.65 and 0.68, respectively) for the Self-image and Anxiety domains; and weak (coefficient = 0.58) for the Confidence in Health Care domain. CONCLUSIONS: The Glau-QoL questionnaire is a valid and specific HRQoL instrument that demonstrates excellent correlations with disease progression in patients with glaucoma and/or OHT. PMID- 17725615 TI - Visual outcome and cataract development after allogeneic stem-cell transplantation in children. AB - PURPOSE: To report visual functions and prevalence of cataract after haematopoetic stem-cell transplantation (SCT) during childhood and to determine the impact of different conditioning regimes and other possible risk factors. METHODS: Assessment of visual acuity (VA), slit-lamp biomicroscopy of the lenses and examination of the ocular fundii were performed in 79 subjects 2-18 years (median 7 years) after SCT. RESULTS: Best-corrected decimal VA > or = 0.5 was achieved in 152/158 eyes (96%). There was an increased risk of cataract after conditioning with single-dose total body irradiation (s-TBI) or fractionated TBI (f-TBI) compared to busulfan or other chemotherapy (P < 0.001) and an increased risk of developing cataract earlier if treated with s-TBI compared to f-TBI (P < 0.01). The TBI mode did not affect the time to first surgical intervention. Apart from s-TBI and f-TBI, age was found to be an independent risk factor. Cataract also developed in patients prepared with chemotherapy but no patient required surgery. Neither treatment with steroids for 6 months or longer nor history of chronic graft versus host disease (GVHD) influenced cataract development. CONCLUSION: Conditioning with full dose f-TBI compared to s-TBI postpones but does not prevent cataract or cataract surgery while chemotherapy-based conditioning induces less severe cataracts, usually not requiring surgery. Corticosteroids or GVHD do not appear as risk factors. PMID- 17725616 TI - Endogenous endophthalmitis: microorganisms, disposition and prognosis. AB - PURPOSE: Endogenous endophthalmitis is a severe and potentially blinding complication caused by haematogenous spreading of microorganisms. We evaluated the causative microorganisms, disposition to and prognosis of the disease. METHODS: Thirty-one eyes of 28 patients were treated between 1996 and 2006 as the result of an endogenous endophthalmitis. RESULTS: The microorganisms responsible for infection could be identified in 94% of all eyes investigated. Candida isolates were obtained in 15, gram-positive isolates in 11, gram-negative in one and Aspergillus in two of the 29 eyes studied. The majority of patients suffered from severe general disease (immuno-deficiency, severe surgical procedures, diabetes mellitus) and one third were intravenous drug abusers. Only one patient was otherwise healthy. The prognosis depended on the causative microorganisms. Whereas none of the eyes with Candida infection became blind, all except two of the eyes with gram-positive bacteria, Nocardia or Aspergillus infection lost visual function or had to be enucleated. CONCLUSION: Compared to postoperative endophthalmitis, patients with endogenous endophthalmitis are more likely to have Candida isolates. Visual prognosis depends mainly on the underlying microorganisms, and is particularly poor in the case of infection with gram positive bacteria or Aspergillus. PMID- 17725618 TI - Identification of a new hemolysin from diarrheal isolate SSU of Aeromonas hydrophila. AB - A clinical strain SSU of Aeromonas hydrophila produces a potent cytotoxic enterotoxin (Act) with cytotoxic, enterotoxic, and hemolytic activities. A new gene, which encoded a hemolysin of 439-amino acid residues with a molecular mass of 49 kDa, was identified. This hemolysin (HlyA) was detected based on the observation that the act gene minus mutant of A. hydrophila SSU still had residual hemolytic activity. The new hemolysin gene (hlyA) was cloned, sequenced, and overexpressed in Escherichia coli. The hlyA gene exhibited 96% identity with its homolog found in a recently annotated genome sequence of an environmental isolate, namely the type strain ATCC 7966 of A. hydrophila subspecies hydrophila. The hlyA gene did not exhibit any homology with other known hemolysins and aerolysin genes detected in Aeromonas isolates. However, this hemolysin exhibited significant homology with hemolysin of Vibrio vulnificus as well as with the cystathionine beta synthase domain protein of Shewanella oneidensis. The HlyA protein was activated only after treatment with trypsin and the resulting hemolytic activity was not neutralizable with antibodies to Act. The presence of the hlyA gene in clinical and water Aeromonas isolates was investigated and DNA fingerprint analysis was performed to demonstrate its possible role in Aeromonas virulence. PMID- 17725619 TI - Protective role and regulation of Rad9 from the fission yeast Schizosaccharomyces pombe. AB - To assess novel cellular roles and regulation of Rad9 in the fission yeast Schizosaccharomyces pombe, the full-length rad9 gene was cloned into the shuttle vector pRS316, generating pYFRad9. The rad9 mRNA level was significantly increased in the S. pombe cells harboring the plasmid pYFRad9, suggesting that the cloned rad9 gene is functioning. The S. pombe cells harboring pYFRad9 showed higher survival in the minimal media containing nitric oxide (NO)-generating sodium nitroprusside (SNP, 20 muM) and no nitrogen than the vector control cells. SNP and nitrogen starvation notably enhanced the synthesis of beta-galactosidase from the rad9-lacZ fusion gene in the Pap1-positive cells but not in the Pap1 negative cells. The rad9 mRNA level, detected by semi-quantitative reverse transcriptase (RT)-PCR, was elevated in the Pap1-positive cells but not in the Pap1-negative cells by SNP and nitrogen starvation. It was also increased only in the Pap1-positive cells by diethylmaleate, which activates Pap1. Collectively, the results imply that Rad9 plays a protective role against nitrosative and nutritional stress and is positively regulated by NO and nitrogen starvation in a Pap1-dependent manner. PMID- 17725620 TI - Evaluation of phoP and rpoS mutants of Salmonella enterica serovar Typhi as attenuated typhoid vaccine candidates: virulence and protective immune responses in intranasally immunized mice. AB - The attenuation and immunoenhancing effects of rpoS and phoP Salmonella enterica serovar strain Typhi (Salmonella typhi) mutants have not been compared. Here, three S. typhi deletion mutants (phoP, rpoS, and rpoS-phoP double mutant) are constructed and these mutants are characterized with respect to invasiveness, virulence, and protective immune response compared with wild-type Ty2. It was found that phoP and phoP-rpoS deletion mutants are less invasive to HT-29 cells than the wild-type Ty2 and the rpoS single-deleted strain. The LD(50) of immunized mice was higher for phoP than for rpoS mutants, and the highest for the phoP-rpoS double mutant. In addition, all S. typhi mutants showed an increase in the specific serum IgG levels and T-cell-mediated immunity, and showed equal protection abilities against a wild-type Ty2 challenge after two rounds of immunization in BALB/c mice. It is concluded that phoP genes appear to play a more important role than rpoS genes in both cellular invasion and virulence of S. typhi, but not in immunogenicity in mice. Furthermore, the data indicate that the phoP-rpoS double mutant may show promise as a candidate for an attenuated typhoid vaccine. PMID- 17725621 TI - Diversity and geographical distribution of members of the Streptomyces violaceusniger 16S rRNA gene clade detected by clade-specific PCR primers. AB - The Streptomyces violaceusniger 16S rRNA gene clade contains organisms that are of ecological interest and a rich source of novel bioactive metabolites. Improvements in the classification of members of the S. violaceusniger clade made it possible to design, evaluate and use an oligonucleotide primer set to gain an insight into the presence, distribution and taxonomic diversity of members of this taxon in environmental samples. In silico testing showed that the primers had a perfect match with representatives of the S. violaceusniger clade. The primers, designated S-S-Svio-66-a-S-20 and S-S-Svio-1274-a-A-20, amplified an approximately 1190-bp stretch of 16S rRNA gene from authenticated members of the S. violaceusniger clade, but not from representatives of other actinomycete taxa. Following amplification of DNA extracted from sediment and soil samples, the sequences of cloned PCR products confirmed the specific amplification of target sequences in 87% of the clones; the use of 16S rRNA gene fragment similarity correlations indicated that the clones represented new species. The primers can be used to facilitate the isolation of novel members of the S. violaceusniger 16S rRNA gene clade by allowing prescreening of environmental samples and the subsequent detection and retrieval of targetted strains through the use of selective isolation procedures. PMID- 17725622 TI - Effect of temperature on composition of the methanotrophic community in rice field and forest soil. AB - Temperature change affects methane consumption in soil. However, there is no information on possible temperature control of methanotrophic bacterial populations. Therefore, we studied CH(4) consumption and populations of methanotrophs in an upland forest soil and a rice field soil incubated at different temperatures between 5 and 45 degrees C for up to 40 days. Potential methane consumption was measured at 4% CH(4). The temporal progress of CH(4) consumption indicated growth of methanotrophs. Both soils showed maximum CH(4) consumption at 25-35 degrees C, but no activity at >40 degrees C. In forest soil CH(4) was also consumed at 5 degrees C, but in rice soil only at 15 degrees C. Methanotroph populations were assessed by terminal restriction fragment length polymorphism (T-RFLP) targeting particulate methane monooxygenase (pmoA) genes. Eight T-RFs with relative abundance >1% were retrieved from both forest and rice soil. The individual T-RFs were tentatively assigned to different methanotrophic populations (e.g. Methylococcus/Methylocaldum, Methylomicrobium, Methylobacter, Methylocystis/Methylosinus) according to published sequence data. Two T-RFs were assigned to ammonium monooxygenase (amoA) gene sequences. Statistical tests showed that temperature affected the relative abundance of most T-RFs. Furthermore, the relative abundance of individual T-RFs differed between the two soils, and also exhibited different temperature dependence. We conclude that temperature can be an important factor regulating the community composition of methanotrophs in soil. PMID- 17725623 TI - Host plant genotype influences survival of hybrids between Eurosta solidaginis host races. AB - Extrinsic, host-associated environmental factors may influence postmating isolation between herbivorous insect populations and represent a fundamentally ecological cause of speciation. We investigated this issue in experiments on hybrids between the host races of Eurosta solidaginis, a fly that induces galls on the goldenrods Solidago altissima and S. gigantea. To do so, we measured the performance of parental host races and their hybrids on five genotypes of S. gigantea and nine genotypes of S. altissima to test hypotheses about how variation in plant genotype affects performance (i.e., fitness) and potentially influences gene flow between these host races. We found that rates of gall induction and of survival to adult emergence by hybrid larvae were significantly lower than those of both parental host races on both host species, adding support to the hypothesis that there is partial postmating isolation between the host races. Hybrid flies significantly varied in their performance across plant genotypes of both host species. A significant interaction between the effects of plant genotype and mating treatment (parental vs. hybrid crosses) on larval performance indicated that the relative suitability of particular plant genotypes differed between the parental host races and their hybrids. These patterns illustrate a poor correspondence between optimal parental and hybrid environments, consistent with the hypothesis that these host races are partially isolated due to extrinsic (ecological) factors. Based on these findings, we discuss the possibility that plant genotypes in which hybrid performance is high can facilitate hybridization and gene flow between partially reproductively isolated populations of herbivorous insects, thus affecting the dynamics of ecological speciation. PMID- 17725624 TI - Promiscuity drives sexual selection in a socially monogamous bird. AB - Many socially monogamous species paradoxically show signs of strong sexual selection, suggesting cryptic sources of sexual competition among males. Darwin argued that sexual selection could operate in monogamous systems if breeding sex ratios are biased or if some males attract highly fecund females. Alternatively, sexual selection might result from promiscuous copulations outside the pair bond, although several recent studies have cast doubt on this possibility, in particular by showing that variance in apparent male reproductive success (number of social young) differs little from variance in actual male reproductive success (number of young sired). Our results from a long-term study of the socially monogamous splendid fairy-wren (Malurus splendens) demonstrate that such comparisons are misleading and do not adequately assess the effects of extra-pair paternity (EPP). By partitioning the opportunity for selection and calculating Bateman gradients, we show that EPP has a strong effect on male annual and lifetime fitness, whereas other proposed mechanisms of sexual selection do not. Thus, EPP drives sexual selection in this, and possibly other, socially monogamous species. PMID- 17725625 TI - Independent evolution of complex life history adaptations in two families of fishes, live-bearing halfbeaks (zenarchopteridae, beloniformes) and poeciliidae (cyprinodontiformes). AB - We have previously documented multiple, independent origins of placentas in the fish family Poeciliidae. Here we summarize similar analyses of fishes in the family Zenarchopteridae. This family includes three live-bearing genera. Earlier studies documented the presence of superfetation, or the ability to carry multiple litters of young in different stages of development in the same ovary, in some species in all three genera. There is also one earlier report of matrotrophy, or extensive postfertilization maternal provisioning, in two of these genera. We present detailed life-history data for approximately half of the species in all three genera and combine them with the best available phylogeny to make inferences about the pattern of life-history evolution within this family. Three species of Hemirhamphodon have superfetation but lack matrotrophy. Most species in Nomorhamphus and Dermogenys either lack superfetation and matrotrophy or have both superfetation and matrotrophy. Our phylogenetic analysis shows that matrotrophy may have evolved independently in each genus. In Dermogenys, matrotrophic species produce fewer, larger offspring than nonmatrotrophic species. In Nomorhamphus; matrotrophic species instead produce more and smaller offspring than lecithotrophic species. However, the matrotrophic species in both genera have significantly smaller masses of reproductive tissue relative to their body sizes. All aspects of these results are duplicated in the fish family Poeciliidae. We discuss the possible adaptive significance of matrotrophy in the light of these new results. The two families together present a remarkable opportunity to study the evolution of a complex trait because they contain multiple, independent origins of the trait that often include close relatives that vary in either the presence or absence of the matrotrophy or in the degree to which matrotrophy is developed. These are the raw materials that are required for either an analysis of the adaptive significance of the trait or for studies of the genetic mechanisms that underlie the evolution of the trait. PMID- 17725626 TI - The quick and the dead: correlational selection on morphology, performance, and habitat use in island lizards. AB - Natural selection is an important driver of microevolution. Yet, despite significant theoretical debate, we still have a poor understanding of how selection operates on interacting traits (i.e., morphology, performance, habitat use). Locomotor performance is often assumed to impact survival because of its key role in foraging, predator escape, and social interactions, and shows strong links with morphology and habitat use within and among species. In particular, decades of study suggest, but have not yet demonstrated, that natural selection on locomotor performance has shaped the diversification of Anolis lizards in the Greater Antilles. Here, we estimate natural selection on sprinting speed and endurance in small replicate island populations of Anolis sagrei. Consistent with past correlational studies, long-limbed lizards ran faster on broad surfaces but also had increased sprint sensitivity on narrow surfaces. Moreover, performance differences were adaptive in the wild. Selection favored long-limbed lizards that were fast on broad surfaces, and preferred broad substrates in nature, and also short-limbed lizards that were less sprint sensitive on narrow surfaces, and preferred narrow perches in nature. This finding is unique in showing that selection does not act on performance alone, but rather on unique combinations of performance, morphology, and habitat use. Our results support the long-standing hypothesis that correlated selection on locomotor performance, morphology, and habitat use drives the evolution of ecomorphological correlations within Caribbean Anolis lizards, potentially providing a microevolutionary mechanism for their remarkable adaptive radiation. PMID- 17725627 TI - Host density impacts relative fitness of bacteriophage Phi6 genotypes in structured habitats. AB - Spatially structured environments may impact evolution by restricting population sizes, limiting opportunities for genetic mixis, or weakening selection against deleterious genotypes. When habitat structure impedes dispersal, low-productivity (less virulent) infectious parasites may benefit from their prudent exploitation of local hosts. Here we explored the combined ability for habitat structure and host density to dictate the relative reproductive success of differentially productive parasites. To do so, we allowed two RNA bacteriophage Phi6 genotypes to compete in structured and unstructured (semi-solid versus liquid) habitats while manipulating the density of Pseudomonas hosts. In the unstructured habitats, the more-productive phage strain experienced a relatively constant fitness advantage regardless of starting host density. By contrast, in structured habitats, restricted phage dispersal may have magnified the importance of local productivity, thus allowing the relative fitness of the less-productive virus to improve as host density increased. Further data suggested that latent period (duration of cellular infection) and especially burst size (viral progeny produced per cell) were the phage "life-history" traits most responsible for our results. We discuss the relevance of our findings for selection occurring in natural phage populations and for the general evolutionary epidemiology of infectious parasites. PMID- 17725628 TI - Associations of Type 1 diabetes mellitus, maternal vascular disease and complications of pregnancy. AB - BACKGROUND: Maternal diabetes increases the risk of pre-eclampsia and abnormalities of fetal growth. We studied the additional impact of maternal vascular disease on these risks. METHODS: The first viable (> 23 weeks) pregnancies of 138 women with Type 1 diabetes mellitus (Type 1 DM), delivered between 1994 and 2003 at the Queen's Medical Centre, Nottingham, UK were studied. Women were divided into groups with and without vascular disease (retinopathy and/or nephropathy and/or pre-existing hypertension). Primary outcomes were pre eclampsia and fetal customized birthweight percentile (cbp) (adjusted for maternal weight, height, parity, ethnicity, gestational age and gender). Secondary outcomes were perinatal outcome (miscarriage, intrauterine or neonatal death), preterm birth, birth asphyxia, neonatal hypoglycaemia and delivery mode. RESULTS: Women with vascular disease were more likely to develop pre-eclampsia (OR 3.5; CI 1.28-9.53) and deliver infants with lower cbp (median 89.0, range 0 100 vs. 98.0, range 0-100; P < or = 0.005). Infants were less likely to be macrosomic (OR 0.46; CI 0.224-0.928) but more likely to have intrauterine growth restriction (IUGR; OR 6.0; CI 1.54-23.33). Women with vascular disease had higher Caesarean section rates (90 vs. 56%, P < or = 0.001). CONCLUSIONS/INTERPRETATION: Women with Type 1 DM and vascular disease are at greater risk of pre-eclampsia and pathological fetal growth. This should influence counselling and merit increased pregnancy surveillance. PMID- 17725629 TI - The transcription factor 7-like 2 (TCF7L2) gene is associated with Type 2 diabetes in UK community-based cases, but the risk allele frequency is reduced compared with UK cases selected for genetic studies. AB - AIMS: Common polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene are strongly associated with Type 2 diabetes. Many studies include a large proportion of cases enriched for family history or young age of diagnosis and may therefore provide an overestimation of the general population risk. We aimed to compare the impact of TCF7L2 in UK community-based Type 2 diabetic subjects with that in subjects ascertained for genetic studies. METHODS: We genotyped the TCF7L2 polymorphism rs7903146 in 1068 cases from two sources: 487 from 10 GP practices and 601 ascertained for genetic studies, and 2099 control subjects from two sources: 1099 parents from a birth cohort (population control subjects) and 300 subjects with normal fasting glucose aged > or = 45 years (community control subjects). RESULTS: When compared with Type 2 diabetes cases ascertained for genetic studies, the risk allele frequency in community-based cases was lower (40 vs. 36%, P = 0.04), but there was no difference in risk allele frequency between community-based control and population-based control subjects (31 vs. 30%, P = 0.61). The T allele of rs7903146 increased Type 2 diabetes risk with an odds ratio (OR) of 1.32 (95% CI: 1.13-1.52; P = 0.0002) in community-based cases, but this OR was lower than the OR of cases enriched for genetic studies [1.58 (95% CI: 1.38-1.80), P = 1.4 x 10(-11)] and the combined OR of meta-analysis of 10 studies to date on rs7903146 [1.48 (95% CI: 1.41-1.54), P < 10(-20)]. CONCLUSION: Common variation in the TCF7L2 gene contributes to Type 2 diabetes risk in UK patients recruited in general practice, but the risk allele frequency may be lower than that in subjects enriched for genetic effects. PMID- 17725630 TI - How does ethnicity affect the association between obesity and diabetes? AB - AIMS: To examine the utility of body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHR) in assessing diabetes risk across different ethnic groups. METHODS: Cross-sectional analysis of data for eight ethnic groups from the 2003-2004 National Health and Nutrition Examination Survey and 2003-2004 Health Survey for England was performed. In 11 624 adults > or = 20 years old, self-reported as US White, US Black, Mexican American, English White, English Black, Bangladeshi, Pakistani, Indian or Chinese the presence of diabetes, defined as self-report of doctor diagnosis or glycated haemoglobin (HbA1c) > 6.1%, was ascertained. Comparisons of proportions were made using chi2-tests. Receiver operating characteristic (ROC) curves were calculated for BMI, WC and WHR predicting diabetes. RESULTS: Other ethnic groups had a higher prevalence of diagnosed diabetes than English Whites. The crude prevalence of diabetes in English Whites of normal weight (BMI < 25 kg/m2) was 3.4%. Higher prevalences were seen in other ethnic groups (5.0-10.9%). Based on ROC curves, both WC and WHR had better discriminating ability for diabetes than BMI for both genders and some ethnic groups. CONCLUSIONS: Ethnic differences exist in the crude prevalence of diabetes, even in those characterized as normal weight by BMI. Thus, clinicians need to exercise caution in interpreting diabetes risk associated with a normal BMI. The use of other anthropometric measures, such as WC or WHR, may improve risk determination across different ethnic groups. More research is needed to determine the thresholds for different anthropometric measures that improve diabetes risk determination. PMID- 17725631 TI - Are lifestyle changes achieved after participation in a screening programme for Type 2 diabetes? The ADDITION Study, Denmark. AB - AIMS: To examine the impact on health-related lifestyle of conducting a targeted stepwise diabetes screening programme. METHODS: A total of 4731 people aged 40-69 years were offered stepwise diabetes screening in part of the Danish arm of the ADDITION-study in the county of Aarhus, Denmark. The screening comprised two main steps: identification of high-risk individuals by a mailed risk score questionnaire, and subsequent testing of high-risk individuals by their general practitioner. Questionnaires on physical exercise [International Physical Activity Questionnaire (IPAQ), short form], smoking habits and alcohol consumption were mailed to the target population 1 month prior to the offer of screening, and at 12 months' follow-up. At follow-up, additional questions regarding perceived changes in dietary habits, smoking, alcohol consumption and exercise were included. Three pairs of comparison groups were analysed. RESULTS: One year after screening, smokers who underwent further testing reduced smoking by one daily cigarette more than people at low risk of diabetes. The rate of smokers was not reduced, and the result was not confirmed by data regarding perceived change. Alcohol intake and exercise were unchanged. Data on perceived changes showed that more people undertook increased exercise in the group at low risk than in the further examined group, but this was not seen when comparing high-risk attenders with non-attenders. Dietary habits were unchanged, except that slightly more people in the group with an abnormal test result reported increase of fruit and vegetable intake and reduction of fat intake compared with the group with a normal test result. CONCLUSION: Only minor and inconsistent impacts on lifestyle was observed 1 year after screening. PMID- 17725632 TI - Oesophageal dysmotility, delayed gastric emptying and gastrointestinal symptoms in patients with diabetes mellitus. AB - AIMS: Gastroparesis is a common gastrointestinal complication in diabetes mellitus, whereas dysfunction in the other gastrointestinal organs has been less thoroughly investigated. Furthermore, it is not known whether there is any relationship between motility and dysmotility between these organs. The aim of this study was to examine whether diabetic patients with gastrointestinal symptoms also have motility disturbances in the oesophagus and stomach and, if so, whether there are any associations between these disturbances. METHODS: Thirty-one patients with diabetes mellitus who complained of gastrointestinal symptoms were asked to complete a questionnaire about their symptoms. They were further investigated with oesophageal manometry and gastric emptying scintigraphy. RESULTS: Fifty-eight per cent of the patients had abnormal oesophageal function, and 68% had delayed gastric emptying. Abdominal fullness was the only symptom that related to any dysfunction, and it was associated with delayed gastric emptying (P = 0.02). We did not find any relationship in motility or dysmotility between the oesophagus and the stomach. CONCLUSION: Oesophageal dysmotility, as well as gastroparesis, are common in patients with diabetes who have gastrointestinal symptoms. It is important to investigate these patients further, to be able to reach an accurate diagnosis and instigate appropriate treatment. Our findings indicate that the oesophagus and the stomach function as separate organs and that pathology in one does not necessarily mean pathology in the other. PMID- 17725633 TI - Islet cell autoantibody levels after the diagnosis of young adult diabetic patients. AB - AIMS: The aim was to determine the course of islet cell antibodies [glutamate decarboxylase (GADA), tyrosine phosphatase-like islet antigen 2 (IA-2A) and islet cell (ICA)] after the diagnosis of the diabetic patient. METHODS: The Diabetes Incidence Study in Sweden (DISS) attempted to prospectively enrol all newly diagnosed diabetic patients aged 15-34 years during 1992 and 1993. C-peptide and autoantibody levels were determined from venous blood samples at diagnosis and again at yearly intervals for 6 years. RESULTS: After the first year, the odds of remaining GADA positive decreased by 9% per year [odds ratio (OR) = 0.91, 95% confidence interval (CI) = 0.85-0.96] while the mean GADA index remained unchanged ( = 0.8, P = 0.37). There was no change in the percentage of subjects testing IA-2A positive after the first year ( = 0.1, P = 0.75). However, the mean index decreased 0.04 per year (95% CI: 0.03-0.05)-a 7.9% decline (95% CI: 5.4 10.4%). The odds of a subject testing positive for ICA decreased by 24% per year (OR = 0.76, 95% CI = 0.70-0.82). The mean ICA levels decreased 0.75 per year (95% CI: 0.66-0.84)-a 16.4% decline (95% CI: 14.1-18.6%). The rate of change in titres for all three autoantibodies was independent of gender, human leucocyte antigen genotype and C-peptide status. CONCLUSIONS: GADA levels remained high while ICA levels declined. In contrast to a previous study, we found that the proportion of IA-2A subjects remaining positive did not decrease after the first year, while the average index decreased slightly. PMID- 17725634 TI - Effect of long-term treatment with rosiglitazone on arterial elasticity and metabolic parameters in patients with Type 2 diabetes mellitus: a 2-year follow up study. AB - AIMS: Thiazolidinediones may influence the atherogenic process by improving cardiovascular risk factors. The present study was designed to determine the long term effect of rosiglitazone on arterial compliance and metabolic parameters in patients with Type 2 diabetes. METHODS: In an open-label, prospective study, 65 diabetic patients received rosiglitazone orally (4-8 mg/day) for 6 months. After 6 months, the patients continued an open follow-up study and were divided into two groups: group 1 included patients continuing rosiglitazone for 2 years, group 2 included patients discontinuing rosiglitazone and receiving other oral glucose lowering agents. Lipid profile, glycated haemoglobin (HbA1c), insulin, C-peptide, fibrinogen, high-sensitivity-CRP and homeostasis model assessment-insulin resistance were measured. Arterial elasticity was assessed using pulse wave contour analysis. RESULTS: In patients treated with rosiglitazone for 2 years: the large artery elasticity index (LAEI) increased from 10.0 +/- 4.6 to 13.9 +/- 4.7 ml/mmHg x 100 after 2 years (P = 0.003). The small artery elasticity (SAEI) index increased significantly from 3.2 +/- 1.2 to 5.1 +/- 1.9 (P < 0.0001). In patients who discontinued rosiglitazone: LAEI did not change after 6 months, but decreased from 12.1 +/- 5.4 to 8.9 +/- 3.9 ml/mmHg x 10 (P < 0.0001) at the end of 2 years. SAEI increased during the first 6 months of treatment, from 3.9 +/- 1.8 to 5.1 +/- 1.5 ml/mmHg x 100 (P < 0.0001) and decreased after discontinuation of rosiglitazone (P = 0.042). CONCLUSIONS: Prolonged treatment with rosiglitazone improved arterial elasticity. However, significant deterioration in LAEI and SAEI was observed in patients who discontinued rosiglitazone. The beneficial vascular effect of rosiglitazone on arterial elasticity was independent of glycaemic control. PMID- 17725635 TI - Adipose tissue and liver lipid metabolism in obese children: role of the body mass index and the presence of acanthosis nigricans. AB - AIMS: The aims of our study were to determine if insulin resistance is associated with increased plasma levels of non-esterified fatty acids (NEFA), glycerol, 3 hydroxybutyrate and triglycerides in obese children. We also studied whether the presence of acanthosis nigricans (AN) led to further alterations in the above parameters. METHODS: A total of 101 children were studied on their first visit to the paediatric endocrine clinic. Seventy-four were obese, 30 of them with AN. The remaining 27 were non-obese healthy children (control group). NEFAs, glycerol, triglycerides, 3-hydroxybutyrate, insulin, leptin, adiponectin and glucose were determined in blood samples obtained after overnight fasting. The insulin resistance index (IRI) was calculated following the homeostasis model assessment (HOMA). Data from the three groups were compared using appropriate statistical tests. RESULTS: No differences in age, sex ratio and pubertal stage were observed among the three groups. The group of children with the highest body mass index (BMI) showed higher plasma levels of insulin and leptin, higher IRI and lower plasma levels of adiponectin. As insulin and IRI increased, NEFA and 3 hydroxybutyrate decreased and triglycerides increased. When obese children were categorized by BMI, the presence of AN further exacerbated these differences. CONCLUSIONS: In obese children, insulin resistance is associated with plasma lipid alterations suggestive of both decreased adipose tissue lipolysis and hepatic beta-oxidation and increased hepatic synthesis of triglycerides. Such a metabolic condition may facilitate fat storage and hinder weight loss. PMID- 17725636 TI - Ethnic differences in diabetic retinopathy. AB - AIMS/HYPOTHESIS: To compare the prevalence of diabetic retinopathy in European, Maori and Pacific peoples with diabetes. METHODS: Biomedical assessment and retinal examination, using photography where possible, was undertaken in 458 (67.5% of eligible) randomly selected household survey participants with known diabetes (168 Europeans, 144 Maori, 149 Pacific people). Glycaemia was measured by glycated haemoglobin, fructosamine and random glucose. RESULTS: In those with Type 2 diabetes, the prevalence of moderate or more severe retinopathy was 4.0% in Europeans, 12.9% in Maori and 15.8% in Pacific people (P = 0.003). There was no significant ethnic difference in the prevalence of retinopathy overall or in that of macular disease. Cataracts were more common in Pacific people (19.3%, 16.4%, 36.6%, respectively, P < 0.001). After adjusting for diabetes duration and ethnicity, Type 1 diabetes was associated with 5.3(1.7-16.4)-fold increase in moderate or more severe retinopathy. Although Maori and Pacific people with Type 2 diabetes were more hyperglycaemic, with higher systolic and lower diastolic blood pressure, in the logistic regression analysis, moderate or more severe retinopathy was associated with diabetes duration, insulin therapy, ethnicity and the extent of renal disease, but not glycaemia. CONCLUSIONS: These data demonstrate that moderate or more severe retinopathy is more common in Polynesians than Europeans. The reasons for this are unclear, but may be related to long-standing hyperglycaemia. PMID- 17725637 TI - QTL analysis of floral traits in Louisiana iris hybrids. AB - The formation of hybrid zones between nascent species is a widespread phenomenon. The evolutionary consequences of hybridization are influenced by numerous factors, including the action of natural selection on quantitative trait variation. Here we examine how the genetic basis of floral traits of two species of Louisiana Irises affects the extent of quantitative trait variation in their hybrids. Quantitative trait locus (QTL) mapping was used to assess the size (magnitude) of phenotypic effects of individual QTL, the degree to which QTL for different floral traits are colocalized, and the occurrence of mixed QTL effects. These aspects of quantitative genetic variation would be expected to influence (1) the number of genetic steps (in terms of QTL substitutions) separating the parental species phenotypes; (2) trait correlations; and (3) the potential for transgressive segregation in hybrid populations. Results indicate that some Louisiana Iris floral trait QTL have large effects and QTL for different traits tend to colocalize. Transgressive variation was observed for six of nine traits, despite the fact that mixed QTL effects influence few traits. Overall, our QTL results imply that the genetic basis of floral morphology and color traits might facilitate the maintenance of phenotypic divergence between Iris fulva and Iris brevicaulis, although a great deal of phenotypic variation was observed among hybrids. PMID- 17725638 TI - Microhabitat variation and sexual selection can maintain male color polymorphisms. AB - Male color polymorphism may be an important precursor to sympatric speciation by sexual selection, but the processes maintaining such polymorphisms are not well understood. Here, we develop a formal model of the hypothesis that male color polymorphisms may be maintained by variation in the sensory environment resulting in microhabitat-specific selection pressures. We analyze the evolution of two male color morphs when color perception (by females and predators) is dependent on the microhabitat in which natural and sexual selection occur. We find that an environment of heterogeneous microhabitats can lead to the maintenance of color polymorphism despite asymmetries in the strengths of natural and sexual selection and in microhabitat proportions. We show that sexual selection alone is sufficient for polymorphism maintenance over a wide range of parameter space, even when female preferences are weak. Polymorphisms can also be maintained by natural selection acting alone, but the conditions for polymorphism maintenance by natural selection will usually be unrealistic for the case of microhabitat variation. Microhabitat variation and sexual selection for conspicuous males may thus provide a situation particularly favorable to the maintenance of male color polymorphisms. These results are important both because of the general insight they provide into a little appreciated mechanism for the maintenance of variation in natural populations and because such variation is an important prerequisite for sympatric speciation. PMID- 17725639 TI - A reappraisal of Bateman's classic study of intrasexual selection. AB - Bateman's (1948) study showing greater variances in number of mates and reproductive success in male than female Drosophila melanogaster is a foundational paper in sexual selection. Here we show for the first time that his methods had flaws, including the elimination of genetic variance, sampling biases, miscalculations of fitness variances, statistical pseudo-replication, and selective presentation of data. We conclude that Bateman's results are unreliable, his conclusions are questionable, and his observed variances are similar to those expected under random mating. Despite our analysis, we do not intend this article as a criticism of Bateman; he accomplished his work without modern computational tools, and his approach was groundbreaking emphasizing the significance of fitness variance for sexual selection. However, this reanalysis has implications for what counts as evidence for sexual selection and we believe that our concerns should be of interest to contemporary students of sexual selection. We call for repetitions of Bateman's study using modern statistical and molecular methods. PMID- 17725640 TI - SAR increases fitness of Arabidopsis thaliana in the presence of natural bacterial pathogens. AB - Given the substantial costs of plant defenses against pathogens, there should be corresponding benefits that prevent resistance from being lost in natural plant populations. Here, we present evidence that systemic acquired resistance (SAR) benefits plants attacked by pathogenic bacteria in nature. In a large field experiment, we found that Arabidopsis thaliana treated with salicylic acid exhibited reduced titers of bacteria in their leaves and elevated fitness relative to controls. Most common members of the culturable bacterial community suffered this decrease, consistent with the role of SAR as a broad spectrum defense. We found no evidence of negative interactions between SAR and jasmonate dependent resistance. Plants treated with jasmonic acid received significantly lower insect damage to their siliques, but exhibited no differences in bacterial growth or fitness relative to controls. Collectively, these data suggest a likely role of pathogenic bacteria in the maintenance of SAR, but not jasmonate dependent resistance, in nature. PMID- 17725641 TI - Functional equivalence of morphologies enables morphological and ecological diversity. AB - Diversity in organismal forms among taxa is thought to reflect distinct selection pressures across environments. The central assumption underlying this expectation is that taxa experiencing similar selection have similar response to that selection. However, because selection acts on trait function, taxa similarity in selection response depends crucially on the relationship between function and morphology. Further, when a trait consists of multiple parts, changes in function in response to selection can result from modification of different parts, and adaptation to the same environment might result in functional but not morphological similarity. Here, we address the extent to which functional and morphological diversity in masticatory apparatus of soricid shrews reflects a shared ecological characteristic of their diet type. We examine the factors limiting morphological variation across shrew species by assessing the relative contribution of trait function (biomechanics of the jaw), ecology, and phylogeny to species similarity in mandibular traits. We found that species that shared diet type were functionally but not morphologically similar. The presence of multiple semi-independently varying traits enabled functional equivalence of composite foraging morphologies and resulted in variable response to selection exerted by similar diet. We show that functional equivalence of multiple morphologies enabled persistence of differences in habitat use (e.g., habitat moisture and coverage) among species that specialize on the same diet. We discuss the importance of developmental and functional integration among traits for evolutionary diversification of morphological structures that generate equivalent functions. PMID- 17725642 TI - Protein transport in chloroplasts - targeting to the intermembrane space. AB - The import of proteins destined for the intermembrane space of chloroplasts has not been investigated in detail up to now. By investigating energy requirements and time courses, as well as performing competition experiments, we show that the two intermembrane space components Tic22 and MGD1 (E.C. 2.4.1.46) both engage the Toc machinery for crossing the outer envelope, whereas their pathways diverge thereafter. Although MGD1 appears to at least partly cross the inner envelope, Tic22 very likely reaches its mature form in the intermembrane space without involving stromal components. Thus, different pathways for intermembrane space targeting probably exist in chloroplasts. PMID- 17725643 TI - Phosphorylation modulates the local conformation and self-aggregation ability of a peptide from the fourth tau microtubule-binding repeat. AB - Phosphorylation of tau protein modulates both its physiological role and its aggregation into paired helical fragments, as observed in Alzheimer's diseased neurons. It is of fundamental importance to study paired helical fragment formation and its modulation by phosphorylation. This study focused on the fourth microtubule-binding repeat of tau, encompassing an abnormal phosphorylation site, Ser356. The aggregation propensities of this repeat peptide and its corresponding phosphorylated form were investigated using turbidity, thioflavin T fluorescence and electron microscopy. There is evidence for a conformational change in the fourth microtubule-binding repeat of tau peptide upon phosphorylation, as well as changes in aggregation activity. Although both tau peptides have the ability to aggregate, this is weaker in the phosphorylated peptide. This study reveals that both tau peptides are capable of self-aggregation and that phosphorylation at Ser356 can modulate this process. PMID- 17725644 TI - Post-translational modifications in the active site region of methyl-coenzyme M reductase from methanogenic and methanotrophic archaea. AB - Methyl-coenzyme M reductase (MCR) catalyzes the methane-forming step in methanogenic archaea. Isoenzyme I from Methanothermobacter marburgensiswas shown to contain a thioxo peptide bond and four methylated amino acids in the active site region. We report here that MCRs from all methanogens investigated contain the thioxo peptide bond, but that the enzymes differ in their post-translational methylations. The MS analysis included MCR I and MCR II from Methanothermobacter marburgensis, MCR I from Methanocaldococcus jannaschii and Methanoculleus thermophilus, and MCR from Methanococcus voltae, Methanopyrus kandleri and Methanosarcina barkeri. Two MCRs isolated from Black Sea mats containing mainly methanotrophic archaea of the ANME-1 cluster were also analyzed. PMID- 17725645 TI - Novel globoside-like oligosaccharide expression patterns in nontypeable Haemophilus influenzae lipopolysaccharide. AB - We report the novel pattern of lipopolysaccharide (LPS) expressed by two disease associated nontypeable Haemophilus influenzae strains, 1268 and 1200. The strains express the common structural motifs of H. influenzae; globotetraose [beta-d GalpNAc-(1-->3)-alpha-d-Galp-(1-->4)-beta-d-Galp-(1-->4)-beta-d-Glcp] and its truncated versions globoside [alpha-d-Galp-(1-->4)-beta-d-Galp-(1-->4)-beta-d Glcp] and lactose [beta-d-Galp-(1-->4)-beta-d-Glcp] linked to the terminal heptose (HepIII) and the corresponding structures with an alpha-d-Glcp as the reducing sugar linked to the middle heptose (HepII) in the same LPS molecule. Previously these motifs had been found linked only to either the proximal heptose (HepI) or HepIII of the triheptosyl inner-core moiety l-alpha-d-Hepp-(1-->2) [PEtn-->6]-l-alpha-d-Hepp-(1-->3)-l-alpha-d-Hepp-(1-->5)-[PPEtn-->4]-alpha-Kdo-(2 ->6)-lipid A. This novel finding was obtained by structural studies of LPS using NMR techniques and ESI-MS on O-deacylated LPS and core oligosaccharide material, as well as electrospray ionization-multiple-step tandem mass spectrometry on permethylated dephosphorylated oligosaccharide material. A lpsA mutant of strain 1268 expressed LPS of reduced complexity that facilitated unambiguous structural determination. Using capillary electrophoresis-ESI-MS/MS we identified sialylated glycoforms that included sialyllactose as an extension from HepII, this is a further novel finding for H. influenzae LPS. In addition, each LPS was found to carry phosphocholine and O-linked glycine. Nontypeable H. influenzae strain 1200 expressed identical LPS structures to 1268 with the difference that strain 1200 LPS had acetates substituting HepIII, whereas strain 1268 LPS has glycine at the same position. PMID- 17725646 TI - The Salmonella enterica serotype Typhi regulator TviA reduces interleukin-8 production in intestinal epithelial cells by repressing flagellin secretion. AB - Unlike non-typhoidal Salmonella serotypes, S. enterica serotype Typhi does not elicit neutrophilic infiltrates in the human intestinal mucosa. The Vi capsule encoding tviABCDEvexABCDE operon (viaB locus) is a S. Typhi-specific DNA region preventing production of interleukin (IL)-8 during infection of intestinal epithelial cells. We elucidated the mechanism by which the viaB locus reduces IL 8 production in human colonic epithelial (T84) cells. A S. Typhi tviABCDEvexABCDE deletion mutant, but not a tviBCDEvexABCDE deletion mutant, elicited increased IL 8 production, which could be reduced to wild-type levels by introducing the cloned tviA regulatory gene. Thus, IL-8 expression in T84 cells was modulated by the TviA regulatory protein, but not by the Vi capsular antigen. Consistent with previous reports, IL-8 secretion by T84 cells was dependent on the presence of the flagellin protein FliC. TviA reduced expression of flhDC::lacZ and fliC::lacZ transcriptional fusions and secretion of FliC in S. Typhi. Introduction of tviA into S. enterica serotype Typhimurium reduced flagellin secretion and IL-8 expression. In conclusion, the viaB locus reduces IL-8 production in T84 cells by a TviA-mediated repression of flagellin secretion. Our data suggest that changes in flagella gene regulation played an important role during evolution of the human-adapted S. Typhi. PMID- 17725647 TI - Changing pattern of candidaemia 2001-2006 and use of antifungal therapy at the University Hospital of Vienna, Austria. AB - A retrospective survey of candidaemia between 2001 and 2006 was performed at the University Hospital of Vienna, a 2200-bed centre with large organ transplantation and haematology-oncology units. The incidence rate of Candida spp. in blood cultures increased from 0.27 cases/1000 admissions in 2001 to 0.77 cases/1000 admissions in 2006 (p <0.005). The incidence of candidaemia caused by Candida albicans and by non-albicans Candida spp. both increased during this period; although there was a trend towards an increased incidence (37%) of non-albicans Candida spp., particularly Candida glabrata, in surgical wards, C. albicans remained the predominant pathogen (63%). In the haematology-oncology unit, C. albicans remained the leading pathogen (23/29 isolates, 79%), followed by Candida tropicalis and C. glabrata (2/29, 7% each), Candida sake and Candida lusitaniae (1/29, 3% each). The overall survival rate was 43.8%, ranging from 32.8% in 2004 to 63.6% in 2002. In total, 108 (33.2%) patients died within 4 weeks of the first isolation of Candida spp. from blood; 58 (54%) of these patients died within the first 7 days, and a further 34 patients died within the next 3 months. Fluconazole was used extensively (24 701.5 defined daily doses), followed by amphotericin B (8981.4 defined daily doses), during 2005. The consumption of antifungal agents increased continuously (p <0.05) because of increased use of voriconazole and caspofungin. Although the numbers of susceptible patients remained unchanged, the net increase in the number of cases of candidaemia warrants a re-evaluation of the risk-factors and the use of improved diagnostic procedures for invasive fungal infections. PMID- 17725648 TI - Evaluation of the Murex HIV Ag/Ab Combination assay when used with dried blood spots. AB - This study evaluated the ability of the Murex HIV Ag/Ab Combination assay to detect human immunodeficiency virus (HIV) antibodies in 12 617 dried blood spots (DBSs) on filter paper. The assay had an overall sensitivity of 99.6% and a specificity of 99.9%. In view of its ability to detect p24 antigen and both HIV-1 and HIV-2 antibodies in samples collected in the form of DBSs, the Murex Ag/Ab Combination assay is suitable for use as a standard screening assay for seroprevalence studies, as well as for routine diagnostic use in clinical laboratories. PMID- 17725649 TI - Identification of Legionella spp. by 19 European reference laboratories: results of the European Working Group for Legionella Infections External Quality Assessment Scheme using DNA sequencing of the macrophage infectivity potentiator gene and dedicated online tools. AB - Identification of Legionella spp. can be achieved by DNA sequencing of the macrophage infectivity potentiator (mip) gene. The External Quality Assurance (EQA) scheme described in this report is the first to assess the proficiency of laboratories using this methodology. The results obtained from two EQA distributions sent to European reference laboratories involved in Legionella outbreak control and environmental monitoring are presented. Each distribution contained a panel of ten coded Legionella strains. All strains were from clinical and environmental sources and were considered to be wild-type strains. Participants used dedicated online tools to compare sequence text files against a database of known Legionella spp. The majority of centres (seven of ten, and 11 of 12) correctly identified all strains tested, in the first and second distributions, respectively. Typically, sequence similarity values of 98-100% were obtained when the test strains were compared with sequences contained in the database. In all but one case, lower values indicated a poor quality sequence. The exception was associated with the identification of a putative new species in the first panel. Genotypic identification of Legionella can be achieved by the use of standard protocols, dedicated identification libraries, and online tools. EQA schemes provide an independent measure of performance, and it is recommended that laboratories performing these techniques participate in such schemes, thereby allowing optimisation of and improvements in their performance. PMID- 17725650 TI - Standard and real-time multiplex PCR methods for detection of trimethoprim resistance dfr genes in large collections of bacteria. AB - Two multiplex PCR (mPCR) methods were developed to screen large collections of trimethoprim-resistant Escherichia coli isolates for the most prevalent resistance determinants. Five common integron-carried genes (dfrA1, dfrA5, dfrA7, dfrA12 and dfrA17) were selected as PCR targets. Primers and conditions for standard mPCRs and real-time mPCRs were selected and tested. Two protocols using essentially the same primer pairs were established. The standard mPCR protocol also included an internal control targeting the E. coli 16S rRNA gene. Both protocols proved to be sensitive and specific for detection of the five selected genes. Screening of three different collections of clinical urinary and blood isolates (n = 368) with the two multiplex methods revealed that the five dfr genes accounted for 75-86% of trimethoprim resistance. The standard mPCR is useful and accessible for most laboratories, while the real-time mPCR requires additional equipment and expensive reagents, but is very convenient for high throughput screening of large collections of bacterial isolates. PMID- 17725651 TI - A case-control study on excessive daytime sleepiness in episodic migraine. AB - Migraine patients often complain of sleepiness, a problem that manifests both during and outside an attack, may impair the quality of life and can lead to potentially harmful situations. Findings from an uncontrolled study suggest that a high percentage of migraineurs experience excessive daytime sleepiness (EDS). We investigated EDS in a case-control study on 100 patients with episodic migraine and 100 age- and sex-matched healthy controls and also assessed sleep quality, anxiety and depression. Although it was found that EDS was more frequent in migraineurs than in controls (14% vs. 5%; odds ratio 3.1; 95% confidence interval 1.1-8.9), the frequency was lower than previously reported. EDS correlated with migraine disability, sleep problems and anxiety. EDS in patients with migraine probably stems from the full constellation of headache-sleep affective symptoms resulting from the complex clinical burden of the disease. PMID- 17725652 TI - Relationship between biofeedback and oxidative stress in patients with chronic migraine. AB - Chronic migraine (1.5.1) is burdened with headache-related disability. During noxious stimulation, changes of cerebral blood flow enhance the release of oxygen free radicals that react with nitric oxide (NO). We investigated the role of biofeedback in limiting migraine disability by influencing oxidative stress. Peroxides, NO and superoxide dismutase (SOD) were analysed in 20 female subjects with chronic migraine and in 20 female healthy controls before and after biofeedback sessions. NO(x) levels (23.7 +/- 4.2 vs. 34.9 +/- 4.6 microm; P < 0.05) and SOD activity (6.5 +/- 1.0 vs. 8.0 +/- 0.7 U/ml; P < 0.05) were lower in migraine sufferers before treatment than in healthy controls, whereas peroxide levels (145.8 +/- 40.3 vs. 78.0 +/- 20.0 microm; P < 0.05) were higher in migraine sufferers before treatment than in healthy controls. In migraine sufferers NO(x) levels (23.7 +/- 4.2 vs. 31.3 +/- 7.1 microm; P < 0.05) and SOD activity (6.5 +/- 1.0 vs. 7.9 +/- 0.9 U/ml; P < 0.05) were lower before than after treatment, whereas peroxide levels (145.8 +/- 40.3 vs. 82.4 +/- 21.1 microm; P < 0.05) were higher before than after treatment. SOD serum activity correlated positively with NO(x) serum levels and negatively with peroxide serum levels in healthy controls and in chronic migraine sufferers before and after biofeedback. The mean Migraine Disability Assessment Score before biofeedback sessions was higher than after treatment (36.9 +/- 13.9 vs. 18.8 +/- 10.4; P < 0.001). The effectiveness of biofeedback in limiting chronic migraine may be related to muscular relaxation associated with decreased oxidative stress accompanied by psychological well-being. PMID- 17725653 TI - Paroxysmal stabbing headache in the multiple dermatomes of the head and neck: a variant of primary stabbing headache or occipital neuralgia? AB - A paroxysmal stabbing or icepick-like headache in the multiple nerve dermatomes, especially involving both trigeminal and cervical nerves, has not been fully explained or classified by the International Classification of Headache Disorder, 2(nd) Edition (ICHD-II). Of patients with acute-onset paroxysmal stabbing headache who had visited the Hallym University Medical Center during the last four years, 28 subjects with a repeated stabbing headache involving multiple dermatomes at the initial presentation or during the course were prospectively enrolled. All patients were neurologically and otologically symptom free. A coincidental involvement of both trigeminal and cervical nerve dermatomes included seven cases. Six cases involved initially the trigeminal and then cervical nerve dermatomes. Five cases showed an involvement of the cervical and then trigeminal nerve dermatomes. The remaining patients involved multiple cervical nerve branches (the lesser occipital, greater occipital and greater auricular). Pain lasted very shortly and a previous history of headache with the same nature was reported in 13 cases. Preceding symptom of an infection and physical and/or mental stress were manifested in seven and six subjects, respectively. All patients showed a self-limited benign course and completely recovered within a few hours to 30 days. Interestingly, a seasonal gradient in occurrence of a stabbing headache was found in this study. A paroxysmal stabbing headache manifested on multiple dermatomes can be explained by the characteristics of pain referral, and may be considered to be a variant of primary stabbing headache or occipital neuralgia. PMID- 17725655 TI - White sponge naevus: improvement with tetracycline mouth rinse: report of four cases. PMID- 17725654 TI - Overexpression of the autoantigen IA-2 puts beta cells into a pre-apoptotic state: autoantigen-induced, but non-autoimmune-mediated, tissue destruction. AB - IA-2 is a major autoantigen in type 1 diabetes and autoantibodies to it have become important diagnostic and predictive markers. IA-2 also is an intrinsic transmembrane component of dense core secretory vesicles and knock-out studies showed that IA-2 is a regulator of insulin secretion. Here we show that overexpression of IA-2 puts mouse insulinoma MIN-6 beta cells into a pre apoptotic state and that exposure to high glucose results in G2/M arrest and apoptosis. Molecular study revealed a decrease in phosphoinositide-dependent kinase (PDK)-1 and Akt/protein kinase B (PKB) phosphorylation. Treatment of IA-2 transfected cells with IA-2 siRNA prevented both G2/M arrest and apoptosis and increased Akt/PKB phosphorylation. A search for IA-2 interacting proteins revealed that IA-2 interacts with sorting nexin (SNX)19 and that SNX19, but not IA-2, inhibits the conversion of PtdIns(4,5)P2 to PtdIns(3,4,5)P3 and thereby suppresses the phosphorylation of proteins in the Akt signalling pathway resulting in apoptosis. We conclude that IA-2 acts through SNX19 to initiate the pre-apoptotic state. Our findings point to the possibility that in autoimmune diseases, tissue destruction may be autoantigen-induced, but not necessarily immunologically mediated. PMID- 17725656 TI - CD30-postive lymphoproliferative disorder with lesions at depot injection sites, associated with mycosis fungoides and prostatic carcinoma. PMID- 17725657 TI - Sacroiliitis and polyneuropathy during isotretinoin treatment. AB - Isotretinoin, a medication for acne, has been reported to cause a variety of side effects on the musculoskeletal system. We present a case of sacroiliitis (a relatively uncommon feature) and sensorimotor demyelinating polyneuropathy, which has been reported previously in only a few cases during isotretinoin therapy. Clinical symptoms were improved after the withdrawal of isotretinoin and the follow-up electrophysiological study performed 2 years after the initial diagnosis of polyneuropathy showed mild improvement. Dermatologists are advised to be alert to symptoms of polyneuropathy and sacroiliitis during treatment with isotretinoin. PMID- 17725658 TI - Multiple localized granuloma annulare: ultraviolet A1 phototherapy. PMID- 17725659 TI - Nodular vasculitis: an indicator for ELISpot screening for tuberculosis? PMID- 17725660 TI - Localized pemphigoid (pretibial type) with IgG antibody to BP180 NC16a domain successfully treated with minocycline and topical corticosteroid. PMID- 17725662 TI - An unusual manifestation of linear scleroderma 'en coup de sabre' on the vertex and frontoparietal regions. PMID- 17725661 TI - Black henna tattoos: coexisting rubber and para-phenylenediamine allergy? PMID- 17725663 TI - Successful application of tissue-engineered skin to refractory ulcers. AB - In this study, the effectiveness of a tissue-engineered skin (Activskin; Aierfu, Xi'an, China) was evaluated for the treatment of various refractory ulcers. These ulcers were treated with Activskin after debridement and irrigation with saline. A second application of Activskin was essential if the first application failed to persist on the wounds. Clinical efficacy and safety were assessed at regular clinic visits during 6 months of follow-up. All 11 treated patients improved with Activskin. The ulcers healed by inward migration from the wound edge. The average healing time was 27.8 days. No recurrent ulceration or other adverse events were observed during follow-up. These results provide preliminary evidence that Activskin is safe and effective in the management of refractory ulcers. PMID- 17725664 TI - Effects of calcitonin gene-related peptide on apoptosis of peripheral blood mononuclear cells from patients with systemic lupus erythematosus. AB - BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease with abnormal apoptosis and autoantibody production. Calcitonin gene-related peptide (CGRP) is a neuropeptide produced by the central and peripheral nervous systems and by endocrine cells. It can influence cell death in thymocytes and cultured smooth muscle cells, and inhibits the production of interleukin (IL)-2, which inhibits apoptosis. AIMS: To investigate the effects of calcitonin gene-related peptide (CGRP) on apoptosis of peripheral blood mononuclear cells (PBMCs) from patients with SLE. METHODS: The percentage of apoptosis of PBMCs from patients with SLE and healthy blood donors were examined using annexin-V/propidine iodide staining 48 h after culturing with CGRP and/or its receptor antagonist CGRP(8-37) at various concentrations. IL-2 activity in culture supernatants was determined using the incorporation of 3H-TdR by the IL-2-dependent cell line CTLL and evaluated by ELISA. RESULTS: The percentage of spontaneous apoptosis of PBMCs from patients with SLE was higher than that of healthy blood donors (34.18 +/- 2.86 vs. 18.23 +/- 0.81, P < 0.001). CGRP, at all tested concentrations, had no effect on apoptosis of PBMCs from healthy blood donors, but significantly inhibited apoptosis of PBMCs from patients with SLE at concentrations of >or= 0.5 x 10(-8) mol/L (0.5 x 10(-8) mol/L: 32.01 +/- 3.98 vs. 34.18 +/- 2.86, P < 0.05; 1.0 x 0(-8) mol/L: 26.76 +/- 2.69 vs. 34.18 +/- 2.86, P < 0.001; 1.5 x 10(-8) mol/L: 25.97 +/- 2.65 vs. 34.18 +/- 2.86, P < 0.001), and the effect plateaued at 1.0 x 10(-8) mol/L, at which level inhibition was not significantly increased with increasing concentration. However, CGRP, at any concentration tested, could not reduce the rate of apoptosis of PBMCs from patients with SLE to the normal range. There were significant positive relationships between the effect of CGRP, on apoptosis of PBMCs and SLE Disease Activity Index (0.5 x 10(-8) mol/L: r(s) = 0.328, P < 0.05; 1.0 x 10(-8) mol/L: r(s) = 0.431, P < 0.01; 1.5 x 10(-8) mol/L: r(s) = 0.419, P < 0.01). CGRP(8-37) itself had no effect on apoptosis, but was able to block the effects of CGRP on PBMCs (0.5 x 10(-8) mol/L: 32.01 +/- 3.98 vs. 33.12 +/- 2.37, P < 0.05; 1.0 x 10(-8) mol/L: 26.76 +/- 2.69 vs. 34.73 +/- 2.32, P < 0.001; 1.5 x 10(-8) mol/L: 25.97 +/- 2.65 vs. 35.25 +/- 3.37, P < 0.001). There was no effect of CGRP on IL-2 production. CONCLUSIONS: These results indicate that CGRP plays an important role in the apoptosis of PBMCs from patients with SLE via its receptor; low plasma levels of CGRP may cause accelerated apoptosis. This regulation does not seem to be related to IL-2. PMID- 17725665 TI - A case of agminated lentiginosis with multiple cafe-au-lait macules. AB - Agminated lentiginosis is an unusual pigmentary disorder, characterized by numerous lentigines grouped within an area of normal skin. The pigmented macules are often in a segmental distribution within a sharp demarcation at the midline. We encountered a 28-year-old woman with an unusual combination of multiple cafe au-lait macules and diffuse numerous lentigines involving the right cheek and ipsilateral upper thorax with sharp demarcation at the midline. The multiple lentigines extended bilaterally over the back in a peppered distribution. There were 21 cafe-au-lait macules on both arms, and the trunk and buttocks; however, there were no Lisch nodules, neurofibromas, or any other clinical manifestations for neurofibromatosis. Histopathology of a macule revealed the features of lentigo. PMID- 17725666 TI - Multifocal segmental hyperthermic and hyperhidrotic naevus flammeus: a peculiar variant of eccrine angiomatous hamartoma? AB - Eccrine angiomatous hamartoma (EAH) is a lesion that tends to appear as a plaque or nodular single lesion that may be painful and/or hyperhidrotic. Histopathologically, EAH is manifested by lobules of mature eccrine glands and ducts closely associated with well-differentiated, thin-walled blood vessels. Rarely, EAH can present as a macular hyperhidrotic lesion following a segmental distribution. PMID- 17725667 TI - Hairdressing and the prevalence of scalp disease in African adults. AB - BACKGROUND: Anecdotal reports suggest that certain scalp disorders are common in Africans and may be associated with hairstyles. OBJECTIVES: This study of 874 African adults in Cape Town was performed to test this hypothesis. METHODS: A questionnaire was administered and scalp examinations performed, after ethics approval. RESULTS: Participants included 30.9% men and 69.1% women (median age 36.1 years, range 18-99). Most men had natural hair: 91.7% vs. 24.3% women. The majority of men had recent haircuts (< 4 weeks): 74.8% vs. 9.9% women. The overall prevalence of acne (folliculitis) keloidalis nuchae (AKN) was 3.5%: higher in men than women (10.5% vs. 0.3%). AKN prevalence was not associated with whether clippers or blades were used. However, it was associated with haircut symptoms. Haircut-associated symptoms, i.e. at least one episode of transient pimples (or crusts) and bleeding (however small) were reported in 37% and 18.9% of men, respectively. The latter may have implications for disease transmission. Most women (58.7%) had chemically treated hair (49.2% relaxed and 9.6% permed hair) vs. 2.3% men. The prevalences of traction alopecia (TA) and central centrifugal cicatricial alopecia (CCCA) were 22.6% and 1.9%: higher in women (31.7% vs. 2.2% and 2.7% vs. 0%, respectively). CCCA was highest in women > 50 years (6.7% vs. 1.2%). TA prevalence was highest if the usual hairstyle was extensions attached to relaxed hair (48%). CONCLUSION: We found associations between specific scalp diseases, hairstyles, gender, and age. These associations need further study, better to elucidate determinants and to improve disease prevention and treatment. PMID- 17725668 TI - A clinical assessment of a patch test kit marketed to U.K. hairdressers for detecting hair dye allergy. AB - BACKGROUND: In 2004 a U.K.-based company developed and marketed a patch test kit (Colourstart); Trichocare, Ridgmont, Beds, U.K.) for use by hairdressers. It is intended to assess whether clients have a 'problem with hair dye' and promotes itself as the 'only practical solution to sensitivity testing'. However, a patient presented with a hair dye reaction that had not been detected while using this patch test system. OBJECTIVES: To assess the Colourstart system in the next seven consecutive patients presenting with a history of adverse reactions to hair dyes. METHODS: The Colourstart system was tested in parallel with commercially available hair dye patch test reagents, where applicable. RESULTS: Only three of seven patients allergic to p-phenylenediamine were detected using this system and one patient allergic to toluene-2,5-diamine sulphate was not detected using this system. CONCLUSIONS: The results raise concerns about the sensitivity of this kit for consumer protection, but also wider questions about the regulation, use and interpretation of 'home diagnostic patch test kits' in general. PMID- 17725670 TI - Pathophysiology of nocturnal scratching in childhood atopic dermatitis: the role of brain-derived neurotrophic factor and substance P. AB - BACKGROUND: Childhood atopic dermatitis (AD) is a distressing disease associated with pruritus and sleep disturbance. The pathophysiology of pruritus is complex and various neuropeptides may be involved. OBJECTIVE: To evaluate whether or not brain-derived neurotrophic factor (BDNF) and substance P are associated with disease severity, quality of life and nocturnal scratching in AD. METHODS: Patients with AD aged under 18 years were recruited. Disease severity was assessed with the SCORing Atopic Dermatitis (SCORAD) index, and quality of life with the Children's Dermatology Life Quality Index (CDLQI). Concentrations of plasma BDNF, substance P, AD-associated chemokines [cutaneous T-cell attracting cytokine (CTACK), thymus and activation regulated chemokine (TARC)], serum total IgE and eosinophil counts were measured in these patients. All children were instructed to wear the DigiTrac monitor on their dominant wrist while sleeping. The monitor was programmed to record limb motion between 22.00 and 08.00 h the following morning. RESULTS: Twenty-eight children with AD [mean (SD) age 11.1 (3.3) years] were recruited. The mean (SD) SCORAD was 48.1 (21.5) and CDLQI was 8.7 (5.4) in the patients with AD. Their mean (SD) plasma concentrations of BDNF, substance P, CTACK and TARC were 1798 (935), 94 (42), 1424 (719) and 824 (1000) pg mL(-1), respectively. BDNF was significantly correlated with SCORAD (r = 0.478, P = 0.010) and CDLQI (r = 0.522, P = 0.004), whereas substance P showed significant correlation only with CDLQI (r = 0.441, P = 0.019). BDNF and substance P were also significantly correlated with the average (r = 0.905, P < 0.001 and r = 0.925, P < 0.001) and frequency-specific (r = 0.826, P < 0.001 and r = 0.870, P < 0.001) nocturnal wrist activities measured by DigiTrac. However, there was no correlation between BDNF or substance P and the subjective symptoms of pruritus or sleep-loss scores as reported by the parents in the SCORAD. In contrast, serum total IgE levels showed significant correlations with the subjective symptoms of pruritus (r = 0.576, P = 0.001) and sleep loss (r = 0.419, P = 0.027). CONCLUSIONS: Serum levels of BDNF and substance P correlate with the clinical score and quality of life score in patients with AD. The strong correlations with nocturnal wrist movements suggest that they may be the pathogenic factors of the annoying symptoms of scratching. PMID- 17725669 TI - Abnormal activator protein 1 transcription factor expression in CD30-positive cutaneous large-cell lymphomas. AB - BACKGROUND: CD30+ cutaneous large-cell lymphomas (CLCL) represent a heterogeneous subgroup of skin lymphomas including primary cutaneous CD30+ anaplastic large cell lymphoma (C-ALCL), lymphomatoid papulosis (LyP), transformed mycosis fungoides (T-MF) and Hodgkin's lymphoma (HL) with cutaneous involvement. The activator protein 1 (AP-1) transcription factor consists of JUN, FOS and other protein families. Recent studies have revealed upregulation of JUNB in both MF and C-ALCL and overexpression of JUNB and CD30 in systemic HL and ALCL. OBJECTIVES: To assess systematically the expression pattern of AP-1 transcription factors in CLCL. METHODS: We analysed paraffin tissue sections from 27 patients with LyP, 10 with C-ALCL, eight with T-MF and two with cutaneous HL by immunohistochemistry with antibodies against c-JUN, JUNB, JUND, c-FOS and RAF-1. We also stained samples from 10 patients with C-ALCL, seven with Sezary syndrome (SS), six with T-MF, three with cutaneous HL, two with LyP and control samples with total and phosphorylated mitogen-activated protein kinase (MAPK) antibodies. Results Positive staining for JUND (++) was observed in 13 cases of LyP (48%), 10 C-ALCL, six T-MF (75%) and two cutaneous HL cases. Positive JUNB protein expression was present in four cases of T-MF (50%), four C-ALCL (44%), three LyP (11%) and two cutaneous HL. Expression of total (p44/42) MAP kinase and phosphorylated p44/42 MAP kinase were detected in nine cases of C-ALCL (90%), seven SS (88%), five T-MF (89%) and three cutaneous HL. Most of these samples also showed positive staining for JUNB. CONCLUSION: These results suggest the presence of abnormal AP-1 protein expression in CLCL, which may be relevant to CLCL. PMID- 17725671 TI - Psoriasis and psoriatic arthritis: separate or one and the same? AB - The presence and severity of skin and joint symptoms in patients with psoriasis and psoriatic arthritis frequently do not correspond, a discrepancy that has raised the question of whether they represent two related but different disease processes. The fact that some agents seem to work preferentially in one state over the other reinforces this idea. However, there are also several agents with combined efficacy against cutaneous and articular inflammation that appear to support the existence of a common aetiology. Here we review the clinical, epidemiological and genetic evidence for and against a common pathogenesis for the two diseases. We then discuss the cellular and molecular targets of their selected therapies and how they potentially implicate effector pathways as a common immunopathogenic mechanism. Finally, we examine a recently proposed model of psoriasis pathogenesis involving type 1 interferon-producing plasmacytoid dendritic cells and how it may provide further clues to the aetiological links between psoriasis and psoriatic arthritis. PMID- 17725672 TI - A novel point mutation in the gene encoding capillary morphogenesis protein 2 in a Japanese patient with juvenile hyaline fibromatosis. PMID- 17725673 TI - The significance of multiple blue-grey dots (granularity) for the dermoscopic diagnosis of melanoma. AB - BACKGROUND: The presence of multiple blue-grey dots (MBGD) is widely used by clinicians to decide if a pigmented lesion should be removed, but only little is known about their significance. OBJECTIVES: To evaluate the significance of MBGD for the dermoscopic diagnosis of melanoma. METHODS: In part 1 we retrospectively evaluated 340 pigmented lesions for the presence and morphological appearance of granularity. One hundred and seventy melanomas were included and matched with 170 benign and dysplastic naevi which were randomly chosen from our collection. In part 2, 3773 lesions were examined prospectively in at-risk patients: all lesions with granularity were recorded, surgically removed and subjected to histopathological examination. RESULTS: In part 1, granularity was found in 26.5% of the benign lesions and 93.5% of melanomas. The presence of granularity, granularity at the periphery, irregularly distributed granularity and granularity in association with red and white colour were statistically highly significant for the diagnosis of melanoma (P < 0.001). In part 2, granularity was found in 1.08% of the 3773 lesions and more frequently in sun-damaged skin. Sensitivity for the diagnosis of melanoma was 85% and specificity 99%. CONCLUSIONS: After the revision of many lesions with MBGD, we concluded that the term 'granularity' better describes this entity. Lesions with irregular granularity (periphery, irregularly distributed) should be removed especially if they are associated with red, blue or white colour. Lesions with a benign dermoscopy pattern which have granularity with a regular appearance and involving only a small portion of the lesion do not require surgical excision. PMID- 17725674 TI - Therapeutic effect of lipoprostaglandin E1 on livedoid vasculitis associated with essential cryoglobulinaemia. PMID- 17725675 TI - Epidermal cell necrosis with direct epidermal infiltration of Epstein-Barr virus (EBV)-encoded small nuclear RNA-positive T lymphocytes in a patient with EBV associated haemophagocytic syndrome. PMID- 17725676 TI - Severe linear form of granuloma annulare along Blaschko's lines preceding the onset of a classical form of granuloma annulare in a child. PMID- 17725677 TI - Designing a validated patient information website: a quality-controlled information portal illustrated by skin cancer. PMID- 17725678 TI - Multidisciplinary evaluation of patients with psoriasis presenting with musculoskeletal pain: a dermatology: rheumatology clinic experience. PMID- 17725679 TI - Orthotopic ileal neobladder reconstruction after renal transplant. AB - Radical cystectomy and urinary diversion is an effective curative treatment for muscle invasive bladder cancer. The orthotopic ileal neobladder has become a favorable choice of urinary diversion as it offers superior quality of life, cosmetic outcome and the potential for normal voiding. We treated two patients with bladder cancer who previously underwent renal transplant for end-stage renal disease. Radical cystectomy and orthotopic ileal neobladder reconstruction was performed in both patients. One patient had two renal transplants and underwent transplant nephrectomy at the time of cystectomy. In the other patient, the native kidneys were still present and the ureters were anastomosed to the neobladder. There is excellent function of the neobladder. There were no increased complications seen in these patients. Our cases demonstrate that an orthotopic ileal neobladder is safe and feasible after renal transplant and should be offered to these patients. PMID- 17725680 TI - Low-turnover bone disease in hypercalcemic hyperparathyroidism after kidney transplantation. AB - Hypercalcemia in persistent secondary hyperparathyroidism after kidney transplantation is considered to result from increased bone resorption. Bone biopsies' studies, however, have never been performed in these patients. Bone biopsies after double tetracycline labeling were obtained from 17 patients with hypercalcemic hyperparathyroidism and an estimated glomerular filtration rate > 30 mL/min/1.73 m2. Serologic bone markers, calcitriol, intact fibroblast growth factor-23 (iFGF-23), and serum and 24h urine concentration of calcium and phosphate were measured in all patients. Tubular maximum for phosphate corrected for GFR (TmP/GFR), and the fractional excretion of calcium (FeCa) were calculated. High-turnover renal osteodystrophy (ROD) was present in nine and low turnover ROD in eight patients. The bone formation rate was significantly associated with bone alkaline phosphatase, c-telopeptide and osteocalcin. In patients with high turnover ROD, osteocalcin was also significantly higher than in patients with decreased bone formation. The FeCa was normal or below normal in 14/17 patients. TmP/GFR was below normal in all patients. Neither intact PTH nor iFGF-23 was associated with TmP/GFR, FeCa or any histomorphometric bone parameter. We conclude that hypercalcemia of posttransplant hyperparathyroidism can be associated with high or low turnover bone disease. Decreased calcium excretion suggests an additive tubular effect on hypercalcemia. PMID- 17725681 TI - The evolution of nonimmune histological injury and its clinical relevance in adult-sized kidney grafts in pediatric recipients. AB - To describe the evolution, risk factors and impact of nonimmune histological injury after pediatric kidney transplantation, we analyzed 245 renal allograft protocol biopsies taken regularly from the time of transplantation to 2 years thereafter in 81 consecutive rejection-free pediatric recipients of an adult sized kidney. Isometric tubular vacuolization was present early after transplantation was not progressive, and was associated with higher tacrolimus pre-dose trough levels. Chronic tubulo-interstitial damage and tubular microcalcifications were already noted at 3 months, were progressive and had a greater association with small recipient size, male donor gender, higher donor age and female recipient gender, but not with tacrolimus exposure. Renal function assessment showed that older recipients had a significant increase in absolute glomerular filtration rate with time after transplantation, which differed from small recipients who showed no increase. It is concluded that progressive, functionally relevant, nonimmune injury is detected early after adult-sized kidney transplantation in pediatric recipients. Renal graft ischemia associated with the donor-recipient size discrepancy appears to be a greater risk factor for this chronic histological injury, suggesting that the exploration of additional therapeutic approaches to increase allograft perfusion could further extend the graft survival benefit of adult-sized kidneys transplanted into small children. PMID- 17725682 TI - Domino heart transplantation involving infants. AB - Domino heart transplantation has been well described in adults, but has not previously been reported in infant patients. We report the successful transplantation of a 'domino' heart from a 3-month-old infant with primary pulmonary hypertension undergoing heart-lung transplantation, into a 3-month-old infant with complex congenital heart disease. Both infants have survived past 1 year post-transplant, and neither infant has experienced any clinically significant allograft-related complications. Echocardiography and cardiac catheterization of the domino heart have consistently demonstrated stable hypertrophy of the right ventricle (RV) and interventricular septum, but good right and left ventricular function. Domino heart transplant surgery may be an effective way to provide 'pre-conditioned' donor hearts to infants urgently in need of heart transplantation. PMID- 17725683 TI - Tacrolimus-induced diabetes in rats courses with suppressed insulin gene expression in pancreatic islets. AB - An animal model of post-transplant diabetes was induced in rats by treating them daily with 0.1 mg/kg body weight of tacrolimus (FK506) in two i.p. injections. Rats developed hyperglycaemia and glucose intolerance after 9 days of treatment. Pancreatic islets, isolated from treated rats on different days, showed a decreased capacity to secrete insulin in response to 20 mM glucose at days 7 and 14. This suppression of insulin secretion was preceded by a reduction of the islet insulin content on day 5 that was progressively decreasing until the end of the treatment (day 14). Islet content of insulin mRNAs, transcribed from rat insulin genes 1 and 2, was strongly suppressed, similar to the insulin content, at days 7 and 14. Islet mass was not strikingly modified by tacrolimus treatment: the DNA content was slightly decreased at the end (day 14) and the rate of islet cell apoptosis slightly increased. Tacrolimus-induced diabetes in the rat seems to be mainly provoked by a decreased insulin gene transcription with little or no alteration of islet mass. This explains that the observed suppression of all the islet and animal parameters studied was completely reversed 2 weeks after interrupting tacrolimus treatment. PMID- 17725684 TI - No association between SNP rs498055 on chromosome 10 and late-onset Alzheimer disease in multiple datasets. AB - SNP rs498055 in the predicted gene LOC439999 on chromosome 10 was recently identified as being strongly associated with late-onset Alzheimer disease (LOAD). This SNP falls within a chromosomal region that has engendered continued interest generated from both preliminary genetic linkage and candidate gene studies. To independently evaluate this interesting candidate SNP we examined four independent datasets, three family-based and one case-control. All the cases were late-onset AD Caucasian patients with minimum age at onset >or= 60 years. None of the three family samples or the combined family-based dataset showed association in either allelic or genotypic family-based association tests at p < 0.05. Both original and OSA two-point LOD scores were calculated. However, there was no evidence indicating linkage no matter what covariates were applied (the highest LOD score was 0.82). The case-control dataset did not demonstrate any association between this SNP and AD (all p-values > 0.52). Our results do not confirm the previous association, but are consistent with a more recent negative association result that used family-based association tests to examine the effect of this SNP in two family datasets. Thus we conclude that rs498055 is not associated with an increased risk of LOAD. PMID- 17725685 TI - Taurine and zebu admixture in Near Eastern cattle: a comparison of mitochondrial, autosomal and Y-chromosomal data. AB - Eight Bos taurus cattle breeds from the Near East region were screened with a Bos indicus (zebu)-diagnostic Y-specific microsatellite (INRA124) to estimate the proportion of zebu Y chromosomes in each population. This value was compared with previously published values for zebu introgression for both the mitochondrial and autosomal gene pools of the same breeds. All breeds revealed considerable levels of introgression from B. indicus cattle when the autosomal data were taken into consideration; this was particularly apparent in cattle populations from Iraq in the east, and declined in the populations further west towards Anatolia. This non random pattern of introgression and admixture is suggestive of the introduction of zebu cattle from the region corresponding to present-day Iran and northern Pakistan. In addition, the maternal and paternal markers demonstrate that the movement of cattle into and within the Near East was complex. PMID- 17725687 TI - Some highlights of research on aging with invertebrates, 2006-2007. AB - The invertebrate model organisms continue to be engines of discovery in aging research. Recent work with Drosophila stem cells has thrown light on their human equivalents, and on the role of stem cells and their niches in the decline in fecundity with age. Inspired by observations of aging in bacteria and yeast, a new theoretical study has revealed evolutionary forces that could favour asymmetry in the distribution of damaged cell constituents at division, and hence pave the way for the evolution of aging and selective maintenance of integrity of the germ line. Mechanisms of nutrient sensing and cell signalling in the response of lifespan to dietary restriction have been elucidated. Powerful invertebrate models of human aging-related disease have been produced, and used to start to understand how the aging process acts as a risk factor for disease. In the near future, studies of invertebrate aging are likely to move away from an exclusive reliance on genetic manipulation towards a more biochemical and physiological understanding of these systems. PMID- 17725686 TI - Mitochondrial haplotypes reveal a strong genetic structure for three Indian sheep breeds. AB - This survey represents the first characterization of mitochondrial DNA diversity within three breeds of Indian sheep (two strains of the Deccani breed, as well as the Bannur and Garole breeds) from different geographic regions and with divergent phenotypic characteristics. A 1061-bp fragment of the mitochondrial genome spanning the control region, a portion of the 12S rRNA gene and the complete phenyl tRNA gene, was sequenced from 73 animals and compared with the corresponding published sequence from European and Asian breeds and the European Mouflon (Ovis musimon). Analysis of all 156 sequences revealed 73 haplotypes, 52 of which belonged to the Indian breeds. The three Indian breeds had no haplotypes in common, but one Indian haplotype was shared with European and other Asian breeds. The highest nucleotide and haplotype diversity was observed in the Bannur breed (0.00355 and 0.981 respectively), while the minimum was in the Sangamneri strain of the Deccani breed (0.00167 and 0.882 respectively). All 52 Indian haplotypes belonged to mitochondrial lineage A. Therefore, these Indian sheep are distinct from other Asian and European breeds studied so far. The relationships among the haplotypes showed strong breed structure and almost no introgression among these Indian breeds, consistent with Indian sheep husbandry, which discourages genetic exchange between breeds. These results have implications for the conservation of India's ovine biodiversity and suggest a common origin for the breeds investigated. PMID- 17725688 TI - Sexual selection affects lifespan and aging in the seed beetle. AB - Sexual selection in general, and sexual conflict in particular, should affect the evolution of lifespan and aging. Using experimental evolution, we tested whether removal of sexual selection leads to the evolution of accelerated or decelerated senescence. We subjected replicated populations of the seed beetle Callosobruchus maculatus to either of two selection regimes for 35 generations. These regimes either allowed (polygamy) or removed the potential (monogamy) for sexual selection to operate. To test for the evolution of intrinsic differences between the two selection regimes, we assayed longevity in replicate cohorts of virgin females and males. Virgin females from populations evolving under sexual selection had reduced lifespan as predicted by the sexual conflict theory of aging. However, this reduction was due to increased baseline mortality rather than an increase in age-specific mortality rates with age. We discuss these findings in light of other data from this model system and suggest that system specific idiosyncrasies may often modulate the general effects of male-female coevolution on the evolution of aging. PMID- 17725689 TI - Apolipoprotein E genotype influences vertical transmission of herpes simplex virus type 1 in a gender specific manner. AB - There is growing evidence that herpes simplex virus type 1 (HSV-1), together with the apolipoprotein E 4 (APOE4) allele, contribute to the pathogenesis of Alzheimer's disease (AD), although the mechanism of their interaction remains uncertain. Here we show that the combination of inherited APOE genotype and vertical transmission of HSV-1 confers a differential risk of brain infection. These risk factors are known to be associated with AD. PMID- 17725691 TI - Shared environmental factors associated with telomere length maintenance in elderly male twins. AB - During aging, chromosome ends, or telomeres, gradually erode or shorten with each somatic cell division. Loss of telomere length homeostasis has been linked to age related disease. Remarkably, specific environmental assaults, both physical and psychological, have been shown to correlate with shortened telomeres. However, the extent that genetic and/or environmental factors may influence telomere length during later stages of lifespan is not known. Telomere length was measured in 686 male US World War II and Korean War veteran monozygotic (MZ) and dizygotic (DZ) twins (including 181 MZ and 125 DZ complete pairs) with a mean age of 77.5 years (range 73-85 years). During the entire process of telomere length measurement, participant age and twin status were completely blinded. White blood cell mean telomere length shortened in this elderly population by 71 base pairs per year (P < 0.0001). We observed no evidence of heritable effects in this elderly population on telomere length maintenance, but rather find that telomere length was largely associated with shared environmental factors (P < 0.0001). Additionally, we found that individuals with hypertension and cardiovascular disease had significantly shorter telomeres (P = 0.0025 and 0.002, respectively). Our results emphasize that shared environmental factors can have a primary impact on telomere length maintenance in elderly humans. PMID- 17725690 TI - Sex differences in survival and mitochondrial bioenergetics during aging in Drosophila. AB - The goal of this study is to test the role of mitochondria and of mitochondrial metabolism in determining the processes that influence aging of female and male Drosophila. We observe that Drosophila simulans females tended to have shorter lifespan, higher levels of hydrogen peroxide production and significantly lower levels of catalase but not superoxide dismutase compared to males. In contrast, mammalian females tend to be longer lived, have lower rates of reactive oxygen species production and higher antioxidant activity. In both Drosophila and mammals, mitochondria extracted from females consume a higher quantity of oxygen when provided with adenosine diphosphate and have a greater mtDNA copy number than males. Combined, these data illustrate important similarities between the parameters that influence aging and mitochondrial metabolism in Drosophila and in mammals but also show surprising differences. PMID- 17725693 TI - Two pioneering physicians depart. PMID- 17725694 TI - Hemodynamic and metabolic changes during exercise in calves with total artificial hearts of different sizes yet similar output. AB - To evaluate the effects of downsizing of the total artificial heart (TAH), we compared the anaerobic threshold (AT) values in calves with two different types of TAH (Cleveland Clinic-Nimbus TAH and the downsized MagScrew TAH). Exercise studies were performed using a treadmill in 12 calves. During the exercise, parameters to obtain the AT were measured. To evaluate the determinants of the AT, a linear regression analysis was performed between AT and potential variables. AT values from 29 studies revealed no significant differences between the two different TAHs, with no significant differences in hemodynamic or oxygen metabolic parameters. AT values correlated well with pump flow/body weight (Q) multiplied by the hemoglobin level, regardless of the TAH used. In conclusion, downsizing of the original TAH design did not reduce AT without any significant differences in hemodynamic or oxygen metabolic parameters during exercise in calves. PMID- 17725695 TI - Flow-induced platelet activation and damage accumulation in a mechanical heart valve: numerical studies. AB - A model for platelet activation based on the theory of damage, incorporating cumulative effects of stress history and past damage (senescence) was applied to a three-dimensional (3-D) model of blood flow through a St. Jude Medical (SJM) bileaflet mechanical heart valve (MHV), simulating flow conditions after implantation. The calculations used unsteady Reynolds-averaged Navier-Stokes formulation with non-Newtonian blood properties. The results were used to predict platelet damage from total stress (shear, turbulent, deformation), and incorporate the contribution of repeated passages of the platelets along pertinent trajectories. Trajectories that exposed the platelets to elevated levels of stress around the MHV leaflets and led them to entrapment within the complex 3-D vortical structures in the wake of the valve significantly enhanced platelet activation. This damage accumulation model can be used to quantify the thrombogenic potential of implantable cardiovascular devices, and indicate the problem areas of the device for improving their designs. PMID- 17725697 TI - Cycle testing of the MagScrew total artificial heart external battery pack. AB - MagScrew total artificial heart (TAH) external battery pack (EBP) cycle bench testing was conducted on two Wilson Greatbatch (Clarence, NY, USA) lithium ion EBPs over a period of 22 months during continuous charge and discharge cycles under a simulated TAH system current requirement. A custom electronic load was developed to simulate the MagScrew current waveforms typically observed during nominal operation. These current load profiles were applied to the EBP under test during a voltage-defined discharge cycle. EBP endurance indicated a 240-min discharge cycle on a new battery diminishing linearly to 175 min after 800 cycles. A second linear trend started at this knee with 150 min of discharge time at 850 cycles until 10 min at 1600 cycles. Even at 1300 cycles, the EBP could still provide enough power for 60 min of nominal operation. In conclusion, the endurance performance of this EBP was satisfactory while exhibiting a predictable wear-out trend. PMID- 17725696 TI - Study on decellularized porcine aortic valve/poly (3-hydroxybutyrate-co-3 hydroxyhexanoate) hybrid heart valve in sheep model. AB - To overcome shortcomings of current heart valve prostheses, novel hybrid valves were fabricated from decellularized porcine aortic valves coated with poly (3 hydroxybutyrate-co-3-hydroxyhexanoate [PHBHHx]). In the mechanical test in vitro, the biomechanical performance of hybrid valve was investigated. In an in vivo study, hybrid valve conduits were implanted in pulmonary position in sheep without cardiopulmonary bypass. Uncoated grafts were used as control. The valves were explanted and examined histologically and biochemically 16 weeks after surgery. The hybrid valve conduits maintained original shapes, were covered by a confluent layer of cells, and had less calcification than uncoated control. The mechanical test in vitro revealed that PHBHHx coating improved tensile strength. The results in vivo indicated that PHBHHx coating reduced calcification and promoted the repopulation of hybrid valve with the recipient's cells resembling native valve tissue. The hybrid valve may provide superior valve replacement with current techniques. PMID- 17725698 TI - Cosmetic improvement in various acute skin defects treated with tissue-engineered skin. AB - Acute skin defects often cause many adverse events such as abnormal pigmentation and scar formation, the satisfactory healing of which remains a significant clinical challenge. Over the past several decades, a number of skin equivalents have been available for clinical purposes to promote wound closure. However, the true values of skin equivalent - tissue-engineered skin (TE-skin) composed of neonatal fibroblasts and keratinocytes - in improving the quality of wound healing are not yet elucidated. A total of 158 patients were enrolled, 129 of which were used in this study. In these patients, acute skin defects were treated with TE-skin as experimental group, and treated with Vaseline primary dressing as control group. The differences in average healing times between the two groups were determined with statistical analysis according to different depths of skin defects. Wound quality, including pigmentation, cicatrization, and pliability, was assessed by investigators from different clinical centers over a 6-month period. The cosmetic outcome of the wound was further evaluated with histological method. In the study, the average time of wound closure in the experimental group was significantly shortened by 6.5 to 20 days according to different depths of skin defects. The cosmetic quality of reconstructed skin was satisfactory, with the patients enjoying better pliability, less abnormal pigmentation, and cicatrization. Safety analysis demonstrated that the wounds treated with TE-skin did not show clinical or laboratory evidence of rejection during the trial. These results indicate that TE-skin is a suitable and clinically effective treatment for various acute skin defects. Furthermore, the TE-skin appears to produce more satisfactory cosmetic results when compared with the conventional therapy. PMID- 17725699 TI - Reconstruction of rabbit corneal epithelium on lyophilized amniotic membrane using the tilting dynamic culture method. AB - Rabbit corneal epithelium was reconstructed using tilting dynamic culture with a self-manufactured, amniotic membrane (AM) supporter and a lyophilized amniotic membrane (LAM). Rabbit corneal epithelial (RCE) cells were cultured and cryopreserved after isolation from the limbus. The second- and third-passage RCE cells were plated onto the epithelial side of the LAM of Ahn's AM supporter. Two days later, the air-liquid interface culture was maintained with third-passage RCE cells for 6 days and second-passage corneal epithelial cells for 9 days. The average viability of thawed RCE cells, assessed using trypan blue dye exclusion, was 77.42%. The reconstructed corneal epithelium was characterized by histological (hematoxylin and eosin) and immunohistochemical staining (proliferating cell nuclear antigen) for light microscopy, and by reverse transcriptase-polymerase chain reaction, glucose assay, and transmission electron microscopy. The basal layer of the reconstructed corneal epithelium was well formed, and the epithelium was tightly constructed due to the increase in cell proliferation and differentiation caused by the tilting dynamic culture, as opposed to static culture. Tilting dynamic culture was useful for the reconstruction of the epithelium using easily damaged epithelial cells and resulted in more stratum cell layers. Moreover, cytokeratin (CK3) mRNA expression in tilting dynamic cultured third-passage RCE cells seeded onto AM was greater than in static cultured third-passage RCE cells. The morphology of the reconstructed corneal epithelium on LAM by tilting dynamic culture for 9 days resembled that of the skin epidermis. This was thought to be because the tilting dynamic culture not only accelerated the proliferation and differentiation of cells by physical or mechanical stimulation, but also ensured that the supply of medium was delivered to the basal cells more efficiently. Thus, the reconstruction of the corneal epithelium using LAM and tilting dynamic culture was considered to be a good in vitro model for autologous or allogeneic transplantation of corneal epithelium and skin epidermis in patients with damaged epithelia. PMID- 17725700 TI - Morphological characteristics and proliferation of keratocytes cultured under simulated microgravity. AB - This study probed the changes of keratocytes cultured under simulated microgravity. Keratocytes were isolated from rabbit corneas using collagenase digestion method. Cells were seeded in a 55-mL capacity high-aspect-ratio vessel (HARV) of rotary cell culture system (RCCS) at a density of 1 x 10(4) cells/mL. Dehydrated bovine acellular corneal stroma (5 x 5 x 1 mm, n = 30) was used as a carrier for keratocyte culture. Rotational speed was set at 15, 20, and 30 rpm in the first, second, and third week of culture, respectively. Histological evaluation showed that keratocytes in simulated microgravity culture grew into carriers, but those under conventional gravity grew on the surface of carriers. Scanning electron microscopic evaluation showed that after 19 days in culture, keratocytes on the carriers were spherical and spread in the spaces among the collagen fibers. Cells were dendritic or spindle shaped, and they developed many foot processes linked with surrounding cells. The absorbance values of the simulated microgravity group were significantly higher (P < 0.01) than that of the conventional group from 10 to 19 days of culture. The RCCS obviously enhanced the proliferation of rabbit keratocytes and facilitated the cells' growth into or on the dehydrated bovine acellular corneal stroma. Cells showed more natural morphology. PMID- 17725702 TI - Oxygenation-ozonation of blood during extracorporeal circulation: in vitro efficiency of a new gas exchange device. AB - We have investigated the performance of a new gas exchange device (GED), named L001, specifically devised for the ozonation of human blood during extracorporeal circulation. This procedure, defined with the acronym "EBOO," means "extracorporeal blood oxygenation-ozonation." The innovative GED is made of microporous, ozone-resistant, polipropylene hollow fibers with an external diameter of 200 microm, a thickness of 50 microm, and a membrane surface area of 0.22 m(2). The material is coated with phosphorylcholine on the external side in contact with the circulating blood, while a gas mixture, necessarily composed of medical oxygen and ozone (about 99 and 1%, respectively), flows inside the fibers in opposite direction. The new GED has been tested by using a buffered saline solution containing KI and by varying several parameters, and it has shown to be very versatile and efficient. Its main characteristics are minimal foreign surface contact, high gas transfer, and negligible priming volume. This device appears to be a practical, nontoxic, and rather inexpensive tool for performing ozonation of blood for already defined human diseases. PMID- 17725701 TI - Characterization of pro-apoptotic effect of liver failure plasma on primary human hepatocytes and its modulation by molecular adsorbent recirculation system therapy. AB - Plasma from patients with liver failure may contain toxic molecules that cause hepatocyte apoptosis and worsen liver disease, suggesting that removal of pro apoptotic factors is an appropriate therapeutic strategy. We investigated the apoptosis of human hepatocytes induced by plasma from patients with both acute and acute-on-chronic liver disease, and the effect of molecular adsorbent dialysis (molecular adsorbent recirculation system [MARS] dialysis) on this. Apoptotic effects of acute and acute-on-chronic liver failure plasmas from 46 patients were assessed on cultured primary human hepatocytes using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) labeling and caspase 3 activation. In 11 patients undergoing MARS dialysis, the pro-apoptotic effect of their plasma was analyzed before and after therapy. Acute liver failure plasma induced more apoptosis than normal plasma (within 4-6 h of culture, a 2.5 fold increase by TUNEL labeling, 1.8-fold by caspase 3 activation), via a pathway involving caspase 8, suggesting involvement of the death-receptor pathway. However, not all acute liver failure plasmas were significantly more pro apoptotic than normal plasma. Plasma from patients with acutely decompensated chronic liver disease induced apoptosis at the same rate as normal plasma. MARS dialysis improved biochemical parameters indicating effective removal of albumin bound molecules, but the apoptotic effects of the plasma were unchanged. Thus, plasma of patients with acute liver failure, compared to normal plasma, induced increased apoptosis of primary human hepatocytes by a caspase-8- and caspase-3 dependent pathway. The apoptosis induced in the presence of liver failure plasma was not reduced by MARS dialysis. PMID- 17725703 TI - Abstracts of the AABB Annual Meeting, October 20-23, 2007, Anaheim, California, USA. PMID- 17725704 TI - The current and future roles of the consultant diabetologist. PMID- 17725705 TI - Rosiglitazone and myocardial infarction: cause for concern or misleading meta analysis? PMID- 17725706 TI - The importance of free fatty acids in the development of Type 2 diabetes. AB - The recent increase in the prevalence of obesity has been associated with a coincident rise in the prevalence of Type 2 diabetes, whereas weight loss has been shown to decrease the risk of Type 2 diabetes. The pathophysiological mechanisms that have been proposed to explain this link are fundamentally concerned with insulin resistance and the decline in pancreatic B-cell function that accompanies an increase in visceral obesity. They involve the rise in the plasma concentrations of free fatty acids (FFAs) that are associated with an increase in fat mass. Elevated levels of FFAs can lead to insulin resistance, and evidence is growing that B-cell function is impaired through lipotoxicity. Factors such as tumour necrosis factor-alpha (TNF-alpha) and adiponectin, released from adipose tissue, can also modulate insulin resistance. Many interventions that are helpful in treating or preventing Type 2 diabetes, such as weight loss and certain pharmacological interventions, reduce circulating FFA concentrations to a greater or lesser extent. Recent study results suggest that peroxisome proliferator-activated receptor (PPAR)gamma agonists have an effect on the development of Type 2 diabetes. However, in light of concerns over the apparent increase in congestive heart failure with PPARgamma agonists, their place in the prevention of Type 2 diabetes remains to be determined. PMID- 17725708 TI - The intake of potatoes and glucose metabolism in subjects at high risk for Type 2 diabetes. PMID- 17725707 TI - A review of the job satisfaction and current practice of consultant diabetologists in England--barriers and successes. AB - AIMS: The project aimed to describe the perceptions of consultant diabetologists about their work, explore models of care, identify problem areas, consider potential solutions, and outline strategic issues for retention and recruitment. METHODS: The study was based on semistructured qualitative interviews with 92 consultant diabetologists, recruited via a purposive sample. Interviews were recorded, transcribed and anonymized, and analysed by the project team, assisted by QSR Nvivo software. RESULTS: The consultant diabetologist role encompasses a diversity of skills/expertise, with differing emphases between individuals. Integration with general medicine is seen by some as crucial to maintaining proficiency in diabetes, and by others as hindering fulfilment of other roles. Successful team working across organizational boundaries is recognized as essential to effective services, but often impeded by the continuous reorganization and competitive culture of the National Health Service. Significant differences between consultant diabetologist perspectives of primary care colleagues and of primary care trusts emerged. Some consultants have adopted innovative working approaches, adapting national guidance to local environments, but there is general resistance to adopting centrally imposed solutions. Training programmes are not sufficiently explicit about the core skills/attributes required of consultant diabetologists. CONCLUSIONS: The skills of specialist teams are not fully exploited. Competing calls on time could be addressed by encouraging multifaceted consultant teams, allowing individuals to concentrate in specific areas. Clear definition of core skills required by consultant diabetologists underpins training programme development. Collaboration in cross boundary services reflecting local needs is impeded by competition between sectors. Protected time is necessary for cultivating multidisciplinary teams, cross-boundary partnerships and effective, relevant education programmes. Specialist training must reflect the changing role of consultant diabetologists, and include role-specific programmes. PMID- 17725709 TI - Hyperglucagonaemia is not a primary metabolic defect in non-diabetic first-degree relatives from Type 2 diabetic families. PMID- 17725710 TI - The diagnosis of diabetes. PMID- 17725712 TI - Voltage-gated ion channel Kv4.3 is associated with Rap guanine nucleotide exchange factors and regulates angiotensin receptor type 1 signaling to small G protein Rap. AB - The voltage-gated potassium channel Kv4.3 was coexpressed with its beta-subunit Kv channel-interacting protein 2 and the angiotensin type 1 receptor in HEK-293 cells. Proteomic analysis of proteins coimmunoprecipitated with Kv4.3 revealed that Kv4.3 is associated with Rap guanine nucleotide exchange factors MR-GEF and EPAC-1. Previously, we demonstrated that Kv4.3 interacts with the angiotensin type 1 receptor in HE293 cells and cardiac myocytes. On the basis of this, we investigated the angiotensin type 1 receptor signaling to small G-proteins Ras and Rap-1 in the presence and absence of the Kv4.3-Kv channel-interacting protein 2 macromolecular complex. Ras activation was not significantly affected by coexpression of Kv4.3 and Kv channel-interacting protein 2. Ras exhibited a rapid activation-inactivation pattern with maximum activity at 2.5 min after addition of angiotensin II. In contrast, activation of Rap-1 was affected dramatically by coexpression of Kv4.3 and Kv channel-interacting protein 2 with the angiotensin type 1 receptor. In the absence of Kv4.3 and Kv channel-interacting protein 2, stimulation of the angiotensin type 1 receptor resulted in steady activation of Rap-1 that reached a plateau 25 min after addition of angiotensin II. In the presence of Kv4.3 and Kv channel-interacting protein 2, Rap-1 reaches a maximum activity 2.5 min after addition of angiotensin II and then deactivates rapidly, demonstrating a pattern of activation similar to that of Ras. Our findings show that Kv4.3 regulates angiotensin type 1 receptor signaling to the small G-protein Rap-1. PMID- 17725713 TI - The use of recombinant protein and RNA interference approaches to study the reproductive functions of a gonad-stimulating hormone from the shrimp Metapenaeus ensis. AB - Although the crustacean crustacean hyperglycemic hormone/molt-inhibiting hormone/gonad-inhibiting hormone neuropeptides have been studied extensively in the last two decades and several neuropeptides from the shrimp Metapenaeus ensis have been cloned, the functions of most of these neuropeptides remained putative. In this article, we describe the use of recombinant protein and an RNA interference approach to study the reproductive function of the previously reported molt-inhibiting hormone (MeMIH-B) in M. ensis. When hepatopancreas and ovary explants were cultured in medium containing recombinant MeMIH-B, the vitellogenin gene (MeVg1) expression level was upregulated in a dose-dependent manner, reaching a maximum in explants treated with 0.3 nm recombinant MeMIH-B. Shrimp injected with recombinant MeMIH-B showed an increase in vitellogenin gene expression in the hepatopancreas. Moreover, a corresponding increase in the vitellogenin-like immunoreactive protein was detected in the hemolymph and ovary of these females. Injection of MeMIH-B dsRNA into the female shrimp caused a decrease in MeMIH-B transcript level in thoracic ganglion and eyestalk. These shrimp also showed reduction of vitellogenin gene expression in the hepatopancreas and ovary. Furthermore, the hemolymph vitellogenin level was also reduced in these animals. In summary, the results from recombinant protein and RNA interference experiments have demonstrated the gonad-stimulatory function of MeMIH-B in shrimp. PMID- 17725714 TI - Tumor necrosis factor-alpha-induced caspase-1 gene expression. Role of p73. AB - Tumour necrosis factor-alpha (TNF-alpha) is a cytokine that is involved in many functions, including the inflammatory response, immunity and apoptosis. Some of the responses of TNF-alpha are mediated by caspase-1, which is involved in the production of the pro-inflammatory cytokines interleukin-1beta, interleukin-18 and interleukin-33. The molecular mechanisms involved in TNF-alpha-induced caspase-1 gene expression remain poorly defined, despite the fact that signaling by TNF-alpha has been well studied. The present study was undertaken to investigate the mechanisms involved in the induction of caspase-1 gene expression by TNF-alpha. Treatment of A549 cells with TNF-alpha resulted in an increase in caspase-1 mRNA and protein expression, which was preceded by an increase in interferon regulatory factor-1 and p73 protein levels. Caspase-1 promoter reporter was activated by the treatment of cells with TNF-alpha. Mutation of the interferon regulatory factor-1 binding site resulted in the almost complete loss of basal as well as of TNF-alpha-induced caspase-1 promoter activity. Mutation of the p53/p73 responsive site resulted in reduced TNF-alpha-induced promoter activity. Blocking of p73 function by a dominant negative mutant or by a p73 directed small hairpin RNA reduced basal as well as TNF-alpha-induced caspase-1 promoter activity. TNF-alpha-induced caspase-1 mRNA and protein levels were reduced when p73 mRNA was down-regulated by small hairpin RNA. Caspase-5 gene expression was induced by TNF-alpha, which was inhibited by the small hairpin RNA mediated down-regulation of p73. Our results show that TNF-alpha induces p73 gene expression, which, together with interferon regulatory factor-1, plays an important role in mediating caspase-1 promoter activation by TNF-alpha. PMID- 17725715 TI - Modulation of heme and myristate binding to human serum albumin by anti-HIV drugs. An optical and NMR spectroscopic study. AB - Human serum albumin (HSA) has an extraordinary ligand-binding capacity, and transports Fe(III)heme and medium- and long-chain fatty acids. In human immunodeficiency virus-infected patients the administered drugs bind to HSA and act as allosteric effectors. Here, the binding of Fe(III)heme to HSA in the presence of three representative anti-HIV drugs and myristate is investigated. Values of the dissociation equilibrium constant K(d) for Fe(III)heme binding to HSA were determined at different myristate concentrations, in the absence and presence of anti-HIV drugs. Nuclear magnetic relaxation dispersion profiles of HSA-Fe(III)heme were measured, at different myristate concentrations, in the absence and presence of anti-HIV drugs. Structural bases for anti-HIV drug binding to HSA are provided by automatic docking simulation. Abacavir and nevirapine bind to HSA with K(d) values of 1 x 10(-6) and 2 x 10(-6) M, respectively. Therefore, at concentrations used in therapy (in the 1-5 x 10(-6) M range) abacavir and nevirapine bind to HSA and increase the affinity of heme for HSA. In the presence of abacavir or nevirapine, the affinity is not lowered by myristate. FA7 should therefore be intended as a secondary binding site for abacavir and nevirapine. Binding of atazanavir is limited by the large size of the drug, although preferential binding may be envisaged to a site positively coupled with FA1 and FA2, and negatively coupled to FA7. As a whole, these results provide a foundation for the comprehension of the complex network of links modulating HSA-binding properties. PMID- 17725716 TI - Protein kinase CK2 activates the atypical Rio1p kinase and promotes its cell cycle phase-dependent degradation in yeast. AB - Using co-immunoprecipitation combined with MS analysis, we identified the alpha' subunit of casein kinase 2 (CK2) as an interaction partner of the atypical Rio1 protein kinase in yeast. Co-purification of Rio1p with CK2 from Deltacka1 or Deltacka2 mutant extracts shows that Rio1p preferentially interacts with Cka2p in vitro. The C-terminal domain of Rio1p is essential and sufficient for this interaction. Six C-terminally located clustered serines were identified as the only CK2 sites present in Rio1p. Replacement of all six serine residues by aspartate, mimicking constitutive phosphorylation, stimulates Rio1p kinase activity about twofold in vitro compared with wild-type or the corresponding (S > A)(6) mutant proteins. Both mutant alleles (S > A)(6) or (S > D)(6) complement in vivo, however, growth of the RIO1 (S > A)(6) mutant is greatly retarded and shows a cell-cycle phenotype, whereas the behaviour of the RIO1 (S > D)(6) mutant is indistinguishable from wild-type. This suggests that phosphorylation by protein kinase CK2 leads to moderate activation of Rio1p in vivo and promotes cell proliferation. Physiological studies indicate that phosphorylation by CK2 renders the Rio1 protein kinase susceptible to proteolytic degradation at the G(1)/S transition in the cell-division cycle, whereas the non-phosphorylated version is resistant. PMID- 17725717 TI - Transfusion medicine history illustrated. Plasma and prayer in Korea, 1950. PMID- 17725718 TI - How we treat: management of life-threatening primary postpartum hemorrhage with a standardized massive transfusion protocol. AB - Management of massive, life-threatening primary postpartum hemorrhage in the labor and delivery service is a challenge for the clinical team and hospital transfusion service. Because severe postpartum obstetrical hemorrhage is uncommon, its occurrence can result in emergent but variable and nonstandard requests for blood products. The implementation of a standardized massive transfusion protocol for the labor and delivery department at our institution after a maternal death caused by amniotic fluid embolism is described. This guideline was modeled on a existing protocol used by the trauma service mandating emergency release of 6 units of group O D- red cells (RBCs), 4 units of fresh frozen or liquid plasma, and 1 apheresis unit of platelets (PLTs). The 6:4:1 fixed ratio of uncrossmatched RBCs, plasma, and PLTs allows the transfusion service to quickly provide blood products during the acute phase of resuscitation and allows the clinical team to anticipate and prevent dilutional coagulopathy. The successful management of three cases of massive primary postpartum hemorrhage after the implementation of our new massive transfusion protocol in the maternal and fetal medicine service is described. PMID- 17725719 TI - Making sense of malaria. PMID- 17725720 TI - Assessment of cord blood hematopoietic cell parameters before and after cryopreservation. AB - BACKGROUND: The testing of cord blood (CB) progenitor and stem cell units for transplantation suitability involves enumeration of total nucleated cells before freezing. CD34+ cell counts may also be a means of determining suitability. Studies have been conducted to evaluate how specific storage conditions influence cell counts. STUDY DESIGN AND METHODS: CB units were processed by hydroxyethyl starch volume reduction. Cryopreserved-thawed samples were diluted 1:3 without washing. CD34+ cells were measured with three commercially available assay methods. In specific studies, apoptosis-indicating reagents were included. CB units were analyzed for nucleated cells, aldehyde dehydrogenase-containing cells, and progenitor colonies. RESULTS: CD34+ cell levels and nucleated cells were retained during storage in test tubes at 1 to 6 degrees C for 3 days. Cryopreserved-thawed samples showed a reduction in CD34+ cells relative to prefreeze levels with the largest decrease with the Stem-Kit (Beckman Coulter) restricted gating procedure. Prefreeze samples contained minimal numbers of presumed apoptotic cells detected with 7-aminoactinomycin D or SYTO16, but after cryopreservation-thawing there was an increase. Nucleated cell levels determined with a hematology analyzer or flow cytometry were reduced after thawing. Cryopreservation-thawing reduced the percentage of CD34+ cells positive for the presence of aldehyde dehydrogenase and the number of progenitor colonies. These differences were significant. CONCLUSION: These studies indicate that CD34+ cell counts were maintained when CB samples were stored at 1 to 6 degrees C in test tubes for 3 days. Cryopreservation-thawing resulted in changes in a number of parameters including the percentage of CD34+ cells that were aldehyde dehydrogenase(+) and the number of 7-aminoactinomycin D(+) cells and SYTO16(low) cells. PMID- 17725721 TI - Large-scale generation of autologous dendritic cells for immunotherapy in patients with acute myeloid leukemia. AB - BACKGROUND: Mononuclear cells (MNCs) of severely impaired acute myeloid leukemia (AML) patients may be collected by leukapheresis for large-scale generation of dendritic cells (AML-DCs) under good manufacturing practice (GMP) conditions for adoptive immunotherapy. STUDY DESIGN AND METHODS: In five end-stage AML patients, a leukapheresis procedure was performed with a cell separator (either COBE Spectra [Gambro BCT] or Amicus [Baxter]). For large-scale AML-DC generation, the MNCs of a single leukapheresis concentrate were isolated by density gradient and plated into a cell factory under GMP conditions. The AML-DCs were harvested on Day 8 of culture, and their viability, the mature morphology, and the phenotype were evaluated. The AML-DCs were injected subcutaneously into five AML patients up to four times at a biweekly interval. RESULTS: All AML patients entered the leukapheresis procedure with a highly pathologic blood count. In a mean separation time of 198 +/- 33 minutes, a mean of 1.3 +/- 0.2-fold the total blood volume was processed with a white blood cell (WBC) yield of 9 x 10(9) to 70 x 10(9) per collection dependent on the precollection WBC count. After density gradient a mean of 2.2 x 10(9) +/- 0.3 x 10(9) MNCs were plated into a cell factory. This resulted in a mean viable and mature DC yield of 0.01 x 10(9) of MNCs. CONCLUSION: The leukapheresis procedure is a feasible and safe procedure even in patients with hematologic malignancies and highly pathologic blood counts. Sufficient amounts of MNCs can be collected in leukopenic patients and the large-scale generation of AML-DCs in cell factories under GMP conditions yields in an adequate quantity of viable and mature AML-DCs. PMID- 17725722 TI - The donor health assessment questionnaire: potential for format change and computer-assisted self-interviews to improve donor attention. AB - BACKGROUND: The Canadian donor health assessment questionnaire (DHAQ) has developed gradually over many years. The purpose of this study was to determine whether the format and method of administration of the DHAQ influences donor attentiveness. STUDY DESIGN AND METHODS: Between May 2004 and September 2005, a total of 1,397 donors participated in the study by completing the DHAQ by one of three methods: the current Canadian Blood Services (CBS) format and method of administration, which is partly self-administered and partly interviewer administered (Method 1); the DHAQ reformatted to the AABB Uniform Donor Health Questionnaire format and self-administered (Method 2); and an audiovisual computer-assisted self-interview (CASI; Method 3). This was followed by a short, scripted interview assessing recall of 17 specific items queried on the DHAQ. Time to completion of the DHAQ and degree of familiarity with computer use were also assessed. RESULTS: The percentages of donors identifying all 17 items correctly were 9.4, 20.9, and 34.8 percent and the mean percentages recall of items were 53.9, 56.0, and 69.8 percent with DHAQ administration Methods 1, 2, and 3, respectively (p < 0.0001). This difference was largely attributable to the poor recall of items queried as part of a list in Method 1. Mean times to complete the DHAQ were 3.1, 3.8, and 8.1 minutes for Methods 1, 2, and 3, respectively. More than 95 percent of donors had used a personal computer in the past year. CONCLUSION: The current format of the Canadian DHAQ is not optimal for donor attention to specific questions asked as part of a list. Attention was improved by use of AABB uniform donor history questionnaire format and was best with use of a CASI format. PMID- 17725723 TI - Frequent plateletpheresis does not clinically significantly decrease platelet counts in donors. AB - BACKGROUND: In October 2005, the US Food and Drug Administration (FDA) issued draft guidance on collecting platelets (PLTs) by automated methods. The FDA proposed limiting collections to 24 components, rather than 24 procedures, annually with up to 3 components per procedure. The rationale was from literature suggesting frequent PLT collection resulted in significant declines in donor PLT counts. Additional requirements for minimal interdonation intervals were proposed. STUDY DESIGN AND METHODS: Plateletpheresis records at a regional blood center with predonation PLT counts were used to assess the impact of the restriction on PLT collections. They were reviewed to demonstrate the effects of collection frequency, number of products collected, and interdonation interval on donor PLT counts. Total protein and albumin levels were compared in a subset of 24-times-per-year PLT donors and control whole-blood donors. RESULTS: A limit of 24 components would require replacement of approximately 20 percent of the donor base to recover lost components. No clinically important decrease in PLT counts before donation was seen in donors donating multiple PLT components up to 24 times per year, regardless of interdonation interval. No frequent donor was deferred for a PLT count less than 150 x 10(9) per L. Short interdonation intervals were associated with statistically but not clinically important decreases in PLT counts. Protein levels were not distinguishable between PLT donors and controls. CONCLUSION: The proposed restrictions are not required to prevent thrombocytopenia in frequent PLT donors and would adversely impact the supply of apheresis PLTs. Protein levels are maintained in these high-frequency donors. PMID- 17725724 TI - Determinants of repeated blood donation among new and experienced blood donors. AB - BACKGROUND: The maintenance of a safe level of blood supply is provided by a small number of volunteers, and their retention is difficult. The aim of this study was to identify factors predicting repeated blood donation among experienced and new donors. STUDY DESIGN AND METHODS: A random sample of 2,231 donors (2,070 experienced and 161 new) completed a questionnaire assessing psychosocial factors as defined by the most prominent social cognitive theories. Six months later, an objective measure of frequency of registrations to give blood was obtained from the database of the local official agency for blood donation. RESULTS: Logistic regression analysis indicated that for experienced donors, the predictors were intention, perceived control, anticipated regret, moral norm, age, and frequency of blood donation in the past. For new donors, intention and age were the only determinants of behavior. Important differences in the determinants of intention were also noted between experienced and new donors. CONCLUSION: In summary, the results of this study support the idea that distinct promotion strategies should be adopted to increase repeated blood donation among experienced versus new donors. PMID- 17725725 TI - Weak D phenotypes and transfusion safety: where do we stand in daily practice? AB - BACKGROUND: Weak D Types 1, 2, and 3 recipients cannot be immunized when exposed to D antigen. Molecular biology is very efficient to type weak D variants but rarely implemented in daily practice. The serologic typing practice of weak D in a Caucasian patient population was analyzed and a transfusion strategy is proposed. STUDY DESIGN AND METHODS: Samples typed either ddCcee or ddccEe in routine laboratories were tested with the indirect antiglobulin test (D(u) test). D(u)-positive samples were screened for weak D alleles Types 1, 2, and 3 and further tested with immunoglobulin M (IgM) anti-D reagents, used in a fully automated device. RESULTS: A total of 468 of 55,162 samples were found to be ddCcee or ddccEe. Ninety-three expressed weak D after the D(u) test leading to D+ assignment for transfusion. Seventy-three percent of D(u)-positive samples were weak D alleles Type 1, 2, or 3. Almost all weak D Types 1, 2, and 3 were positive with IgM reagents in gel matrix with an automated device. Other variants that could be potentially associated with anti-D alloimmunization, however, were also positive. CONCLUSION: Serology is very sensitive to detect weak D Types 1, 2, and 3, but there is no cutoff to distinguish variants of clinical significance. When molecular analysis is not available, it is proposed that a D+ status for blood recipients found to be weak D with a sensitive method be assigned, except for women of childbearing age or younger, because of the remaining possibility to be partial D or other rare weak D who can be immunized. PMID- 17725727 TI - Prokaryotic versus eukaryotic recombinant Lutheran blood group protein for antibody identification. AB - BACKGROUND: At present, identification of antibodies against high-frequency antigens is limited to reference laboratories having panels of rare red blood cell (RBC) specimens in stock. Antibodies against Lu(b) are among the most frequent clinically relevant antibody specificities directed against high frequency antigens. STUDY DESIGN AND METHODS: Soluble recombinant Lu(b) fusion proteins consisting of the first three N-terminal immunoglobulin superfamily domains and a V5-His tag were generated. Eukaryotic recombinant Lu(b) proteins were isolated from cell culture supernatant of stably transfected HEK293 cells with anti-V5 Sepharose. Prokaryotic Lu(b) fusion proteins were expressed in Escherichia coli, purified by Ni-NTA, and refolded by chromatographic procedures. Ten anti-Lu(b) serum samples, 6 anti-Lu(a) serum samples, 30 serum samples directed against other blood group antigens, 10 serum samples from patients with RBC autoantibodies, and 100 serum samples from randomly selected donors were used for antibody screening. RESULTS: Eukaryotic and prokaryotic recombinant Lu(b) proteins proved to be equally suited for identification of anti-Lu(b). Recombinant Lu(b) protein-based enzyme-linked immunosorbent assay correctly identified samples containing anti-Lu(b) sera, and the titers were at least two times higher than those measured by the gel agglutination-based indirect antiglobulin test. In hemagglutination inhibition assays, recombinant Lu(b) protein neutralized all anti-Lu(b), but none of the other alloantibodies decreased in reactivity. CONCLUSION: Antibody detection systems based on soluble eukaryotic or prokaryotic recombinant blood group proteins have the potential to replace current systems with rare RBCs for identification of alloantibodies against high- or low-frequency antigens. This innovation could bring routine laboratories one step closer to specialized antibody diagnostics. PMID- 17725726 TI - Three new high-prevalence antigens in the Cromer blood group system. AB - BACKGROUND: The Cromer blood group system consists of nine high-prevalence and three low-prevalence antigens carried on decay-accelerating factor (DAF). This report describes three new Cromer high-prevalence antigens, named ZENA, CROV, and CRAM. STUDY DESIGN AND METHODS: Sequence analyses were performed on DNA from three probands whose serum samples each contained an alloantibody to a high prevalence antigen in the Cromer blood group system. Polymerase chain reaction restriction fragment length polymorphism analysis to detect the mutation encoding the CROV- phenotype was performed on 100 Croatian donors. To map the respective epitopes, DAF deletion mutants were tested by immunoblotting with eluates containing the antibodies. RESULTS: In each proband, sequence analysis revealed a single-nucleotide substitution in DAF: ZENA, 726T>G mutation, predicted change His242Gln; CROV, 466G>A mutation, predicted change Glu156Lys; and CRAM, 740A>G mutation, predicted change Gln247Arg. By analysis of DAF deletion mutants, the CROV antigenic determinant mapped to the complement control protein (CCP) domain 2, which is encoded by exon 3, whereas ZENA and CRAM mapped to CCP4, which is encoded by exon 6. CONCLUSION: This study describes three novel high-prevalence antigens in the Cromer blood group system each characterized by a predicted single-amino-acid substitution. The antigens have been assigned the following International Society of Blood Transfusion (ISBT) numbers: ZENA is CROM13, CROV is CROM14, and CRAM is CROM15. PMID- 17725728 TI - Multicolor real-time polymerase chain reaction genotyping of six human platelet antigens using displacing probes. AB - BACKGROUND: Several genotyping methods for six clinically relevant human platelet antigens (HPAs) have been reported. A four-color real-time polymerase chain reaction (PCR) method using displacing probes for genotyping of the six HPAs is described. STUDY DESIGN AND METHODS: Primers and four differently fluorophor labeled displacing probes were designed and synthesized to detect single nucleotide polymorphisms responsible for each of the HPA-1, -2, -3, -4, -5, and 15 genotypes. Two HPA systems were analyzed in a single PCR procedure. After validation with samples of known genotypes, a total of 150 blood samples from healthy donors were genotyped. The results were compared with PCR with sequence specific primers (SSP), PCR-restriction fragment length polymorphism (RFLP), and/or direct DNA sequencing. The frequencies of each HPA allele were calculated. RESULTS: Unequivocal real-time PCR genotyping results were obtained with minimal manual manipulation and carryover contamination. All 150 blood samples were correctly genotyped as confirmed by PCR-SSP, PCR-RFLP, and/or direct DNA sequencing. The allelic frequencies of HPA-1 through -5 and -15 among the Chinese population in Xiamen were comparable with those previously reported with Chinese living in other territories. For each specimen, genotyping of all six HPA biallelic systems was achieved in three tubes of PCR within 90 minutes and with material cost of no more than $1. CONCLUSION: Genotyping of HPA with real-time PCR using displacing probes is more rapid and reliable compared with PCR-SSP and PCR-RFLP methods and is more affordable than existing real-time PCR-based HPA genotyping assays. Thus, our approach is more suitable for routine HPA analysis and ideal for both urgent clinical testing and high-throughput screening. PMID- 17725729 TI - Microcalorimetry: a novel method for detection of microbial contamination in platelet products. AB - BACKGROUND: Measuring heat from replicating microorganisms in culture may be a rapid, accurate, and simple screening method for platelets (PLTs). Microcalorimetry for detection of microorganisms in in vitro contaminated PLT products was evaluated. STUDY DESIGN AND METHODS: Staphylococcus epidermidis, Staphylococcus aureus, Streptococcus sanguinis, Escherichia coli, Propionibacterium acnes, and Candida albicans were inoculated in single-donor apheresis PLTs to achieve target concentrations of 10(5), 10(3), 10, or 1 colony forming units (CFU) per mL of PLTs. Contaminated PLTs in growth medium were incubated at 37 degrees C for 5 days in a calorimeter. Positivity was defined as heat flow of at least 10 microW above the lowest value of the power-time curve. RESULTS: With microcalorimetry, inocula of 10 CFUs per mL PLTs could be detected with the following detection times: S. epidermidis (31.65 hr), S. aureus (24.24 hr), S. sanguinis (7.82 hr), E. coli (7.53 hr), P. acnes (73.57 hr), and C. albicans (43.77 hr). The detection time was less than 4 hr at 10(5) CFUs per mL PLTs for S. aureus, S. sanguinis, and E. coli. Noncontaminated PLTs remained negative. The total heat ranged from 2.8 (S. sanguinis) to 8.3 J (E. coli). The shape of the power-time curve was species-specific and independent from the initial concentration of microorganisms. CONCLUSION: The detection limit of microcalorimetry was 1 to 10 CFUs per mL PLTs. Microcalorimetry is a promising novel method for detection of contaminated PLTs. Applying this method to all PLT products could reduce the frequency of transfusion-related sepsis and prolong the shelf life of PLTs. PMID- 17725730 TI - Platelet counting in platelet concentrates with various automated hematology analyzers. AB - BACKGROUND: Hematology analyzers use impedance, optical, and/or immunologic techniques for counting platelets (PLTs). PLT counting in whole blood has been validated thoroughly; however, this is not the case for PLT counting in PLT concentrates (PCs), in which red cells (RBCs) are absent. Therefore, this study is focused on PLT counting in PCs to study use of ethylenediaminetetraacetate (EDTA), carryover, and accuracy of the analyzers. STUDY DESIGN AND METHODS: In total six hematology analyzers (AcT 8, Beckman Coulter; ADVIA 2,120, Bayer; Cell Dyn 4,000, Abbott; Onyx, Beckman Coulter; K4,500, Sysmex; and XT 2,000i, Sysmex) were tested for PLT counting. PC samples with various PLT concentrations were made (0-1,700 x 10(9)/L) and measured 10 times. Carryover was determined five times. RESULTS: PC samples (1,000 x 10(9) PLTs/L) in EDTA tubes showed significantly higher PLT counts than samples in "dry" tubes for all analyzers except for the Cell-Dyn 4,000 with the impedance technique. Carryover was not more than 0.3 percent for all analyzers. The K4,500 showed the most accurate results, whereas the Cell-Dyn 4,000 with the impedance technique had low accuracy due to an overestimation of more than 20 percent. CONCLUSION: Most tested analyzers seemed to be suitable for counting PLTs in PCs. All hematology analyzers should be validated for counting PLTs in absence of RBCs as is the case in PCs, in addition to validation of PLT counting in whole blood. PMID- 17725731 TI - Effect of gamma irradiation with 30 Gy on the coagulation system in leukoreduced fresh-frozen plasma. AB - BACKGROUND: The aim of this study was to investigate the effect of gamma irradiation with 30 Gy on the coagulation system in leukoreduced fresh-frozen plasma (FFP). STUDY DESIGN AND METHODS: In 74 FFP units that had been stored for 352 +/- 103 days below -30 degrees C, the following variables were determined in parallel in an irradiated and not irradiated half: prothrombin time (PT); activated partial thromboplastin time (APTT); thrombin time; antithrombin III; protein C; protein S; von Willebrand factor antigen; ristocetin cofactor; plasminogen-alpha(2)-antiplasmin; the coagulation factors fibrinogen, factor (F)II, FV, FVII, VIII, F IX, FX, FXI, FXII, FXIII, and activated factor XII (FXIIa); D-dimer; fibrin monomer; thrombin-antithrombin complex; prothrombin fragment 1 + 2 (F1+2); plasmin-alpha(2)-antiplasmin complexes (PAPs); and platelet factor 4. The FVII activity ratio was assayed to quantify activation of FVII. RESULTS: Irradiation with 30 Gy resulted in a reduction of APTT (35.0 +/- 4.1 sec vs. 34.4 +/- 4.1 sec; p = 0.00000006) and PT (89.8 +/- 8.2% vs. 90.7 +/- 8.0%; p = 0.002) and a significant increase of the activities of the coagulation factors FII, FV, FVII, F IX, FX, and FXII. FVIII activity decreased from 118 +/- 31 to 116 +/- 32 percent (p = 0.02). Activation of the coagulation system was shown by an increase in the FVII activity ratio (1.19 +/- 0.29 vs. 1.31 +/- 0.34; p = 0.0000001), FXIIa (0.81 +/- 0.50 ng/mL vs. 0.90 +/- 0.51 ng/mL; p = 0.006), and F1+2 (1.19 +/- 0.20 nmol/L vs. 1.24 +/- 0.20 nmol/L; p = 0.000005) after irradiation with 30 Gy, whereas an increase of PAP (16.2 +/- 11.5 ng/mL vs. 20.2 +/- 12.0 ng/mL; p = 0.0004) demonstrated activation of the fibrinolytic system. No negative influence of irradiation with 30 Gy on inhibitors of coagulation was observed. CONCLUSION: Gamma irradiation of leukoreduced FFPs with 30 Gy results in a significant but very weak activation of the coagulation and fibrinolytic system in FFPs. PMID- 17725732 TI - Interruption of agitation of platelet concentrates: a multicenter in vitro study by the BEST Collaborative on the effects of shipping platelets. AB - BACKGROUND: Transported platelets (PLTs) are not under continuous agitation. The aim of this study was to determine whether PLTs shipped between 24 and 48 hours would be able to maintain a pH(22 degrees C) value of 6.5 at the end of 7 days of storage. STUDY DESIGN AND METHODS: Six laboratories prepared leukoreduced PLTs. PLT pools were divided into low and high PLT concentration with paired shipped (20-43 hr) and unshipped controls. Units were under continuous agitation at 22 +/ 2 degrees C when not being transported. In vitro measures including pH, pO(2), and pCO(2) were determined over 7 days. RESULTS: Ninety-two PLT components from 24 pools were eligible for analysis. One unshipped control and three shipped products failed to maintain a pH(22 degrees C) value of 6.5 through 7 days. In vitro characteristics were maintained slightly better over 7 days of storage in the unshipped control arms. PLT concentration, shipping time, and their interaction were significant determinants of the final pH at the end of storage (p < 0.05). Lactate generation rate increased by 35 +/- 2 (mean +/- SE) micromol per 10(12) PLTs per hour over baseline during shipping (p < 0.0001). After restoration of standard blood banking conditions with agitation, this rate dropped 24 +/- 2 micromol per 10(12) PLTs per hour (p < 0.0001). CONCLUSION: PLTs in plasma shipped for at least 20 to 24 hours maintain a pH(22 degrees C) value of 6.5 for 7 days. A longer shipping time may result in a pH(22 degrees C) value of 6.5. During shipping, glycolysis was up regulated in these PLTs resulting in increased lactic acid production. After restoration of agitation, shipped products down regulated glycolysis. These effects should be accounted for in the development of PLT storage and transportation systems. PMID- 17725733 TI - Implementation of ISBT 128, a quality system, a standardized bar code labeling of blood products worldwide, electronic transfusion pathway: four years of experience in Norway. AB - BACKGROUND: In today's world of multinational disaster relief programs, blood collected and processed in one country may be used in another. A great deal of important information is carried by a blood product label. Given the concerns about safety and traceability, it is important to use globally unique blood product coding and labeling system. STUDY DESIGN AND METHODS: In 1994 the International Society of Blood Transfusion (ISBT) gave a group, ICCBBA (formerly called International Council for Commonality in Blood Banking Automation), the responsibility for implementing a new, safe international system for coding and labeling blood products. This new system is based on 128 bar code symbology and is called ISBT 128. This study describes how ISBT 128 was implemented in blood banks in Norway. RESULTS: As soon as a couple of the most central blood banks implemented the system and started to use it in 2001, they found that it was much easier to handle than their old systems. There were two different software systems being used that were ISBT 128-compliant. The facilities started to export and import blood products to each other. The "foreign" blood products were easily scanned into "own" inventory. They were reluctant to order blood products from blood banks not using ISBT 128. Because of the success in the Department of Immunology and Transfusion Medicine at the University Hospital of Akershus and some other blood banks in Norway, the Norwegian Health Authorities advised all the blood banks to implement ISBT 128. CONCLUSION: The use of ISBT 128 has been a success from the very beginning. PMID- 17725734 TI - AABB survey of transfusion-related acute lung injury policies and practices in the United States. AB - BACKGROUND: Policies and practices with regard to transfusion-related acute lung injury (TRALI) diagnosis, laboratory investigation of TRALI cases, and donor deferral and donor management are not standardized. STUDY DESIGN AND METHODS: A Web-based survey was designed and administered to participating AABB member institutions in July 2006. RESULTS: The survey response rate was highest for donor centers, followed by larger hospital blood banks and transfusion services. Laboratory case workups regularly included HLA Class I and II antibody testing of donors followed less frequently by HNA antibody testing; recipient specimens for leukocyte antigen typing were usually not obtained, even if indicated as part of the planned workup. Several different criteria (i.e., all donors, female donors only, case by case determination) were used to select which donors should be tested. There was agreement that donors should be deferred if implicated in a TRALI case (i.e., antibody-cognate antigen match); however, donor management policies varied in other scenarios. The final diagnosis of TRALI was often (45% 66% depending on institutional type) based on a combination of clinical and serologic findings rather than on adherence to the clinical definition recommended by the Canadian Consensus Conference. Many TRALI policies appeared to be decided on a case-by-case basis at the discretion of the institution's medical director. CONCLUSIONS: There is wide variability in procedures and policies related to the diagnosis of and donor investigation and/or management of TRALI cases. Lack of a consensus approach may partly reflect limitations in understanding of TRALI pathogenesis. The survey suggests that increased education of transfusion medicine practitioners is needed. PMID- 17725735 TI - Hepatitis C antibody intraassay correlation: is retest in duplicate necessary? AB - BACKGROUND: The hepatitis C virus antibody (anti-HCV) can be identified with third-generation immunoassays. The purpose of this study was to define the correlation or agreement between first and second reactive results of anti-HCV microparticle-based enzyme immunoassay (MEIA) and of chemiluminescence assays (ChLIAs) in blood donors, to determine whether repeat testing is necessary. STUDY DESIGN AND METHODS: Commercially available assays, third-generation HCV MEIA (Abbott), third-generation HCV ChLIA (Ortho), and third-generation HCV ChLIA (Abbott), were used to evaluate anti-HCV repeatedly reactive blood obtained from donations made at 23 Mexican blood centers over a period of 1 year. The intraassay correlation between first and second reactive anti-HCV tests with the Pearson r test and the coefficient of variation (CV) were determined. RESULTS: The intraassay correlation of 565 anti-HCV repeatedly reactive samples was 0.996 for the Abbott third-generation HCV MEIA, 0.995 for the Ortho third-generation HCV ChLIA, and 0.993 for the Abbott third-generation HCV ChLIA. The CVs of these assay systems were 2.82, 5.33, and 5.69 percent, respectively. CONCLUSION: A highly significant intraassay correlation between anti-HCV duplicates was found. Specimens with a single reactive anti-HCV result with the Abbott third-generation HCV MEIA, Ortho third-generation HCV ChLIA, and Abbott third-generation HCV ChLIA assays should be considered as positive and need not be retested. Such a change in the algorithm for blood donor screening is feasible because of the availability of highly automated platforms. PMID- 17725736 TI - Immune modulation and microchimerism after unmodified versus leukoreduced allogeneic red blood cell transfusion in cancer patients: results of a randomized study. AB - BACKGROUND: Transfusion of red blood cells (RBCs) has been associated with immunomodulatory effects. Persistence of donor cells in the recipient may be contributive. STUDY DESIGN AND METHODS: A randomized single-center trial was conducted to compare microchimerism and immune responses in 35 patients undergoing cancer surgery and transfused perioperatively with either unmodified RBCs (UN-RBCs, n = 18) or leukoreduced RBCs (LR-RBCs, n = 17). Biologic parameters included microchimerism assessment peripheral blood mononuclear cell (PBMNC) phenotyping, cytokine production by stimulated PBMNCs, FoxP3 gene expression, and T-cell repertoire (TCR) analysis. RESULTS: Microchimerism was documented in 8 of 18 patients after UN-RBC transfusion while absent after LR-RBC transfusion (0/17; p = 0.001). After UN-RBC transfusion, microchimerism was associated with increased interleukin (IL)-10 production (p = 0.02), reduced TCR alteration (p = 0.04), and reduced CD56+ cell counts (p = 0.02) when compared to recipients without evidence for microchimerism. FoxP3 gene expression did not differ significantly between both treatment groups nor with the presence or absence of microchimerism in the UN-RBC group. Finally, after an initial early decrease after surgery and transfusion, IL-12 production increased and more significantly so after UN-RBC transfusion versus LR-RBC transfusion (p = 0.05). CONCLUSION: UN-RBC-induced microchimerism is associated with specific immunomodulatory effects in cancer patients who received transfusions during surgery. PMID- 17725737 TI - Profound thrombocytopenia and survival of hematopoietic stem cell transplant patients without clinically significant bleeding, using prophylactic platelet transfusion triggers of 10 x 10(9) or 20 x 10(9) per L. AB - BACKGROUND: A trigger of 10 x 10(9) per L for prophylactic platelet (PLT) transfusions is generally recommended for stable thrombocytopenic patients who receive chemotherapy, based on studies showing similar incidence, severity, and fatality of bleeding compared with the 20 x 10(9) per L trigger. The outcome of thrombocytopenic nonbleeding patients has not been well described. This retrospective analysis evaluates thrombocytopenia and survival of 381 hematopoietic stem cell transplant (HSCT) patients without clinically significant bleeding, with 10 x 10(9) and 20 x 10(9) per L prophylactic triggers. STUDY DESIGN AND METHODS: A total of 170 patients who received prophylactic PLT transfusions at 20 x 10(9) per L (1997-1998, SP1) and 211 patients who had prophylaxis at 10 x 10(9) per L (1999-2001, SP2) were identified as nonbleeding patients. PLT counts and clinical complications were assessed within 100 days from HSCT. RESULTS: PLT counts less than or equal to 10 x 10(9) per L were found in 69.2 percent of patients in SP2 and 38.3 percent in SP1 (p < 0.001). Profound thrombocytopenia (4+ PLT counts or = 150 ms and evaluated by ECHO and TDI. A responder was defined as a patient with a favorable change in NYHA class and neither HF hospitalization nor death, plus an absolute increase of LVEF > or = 10 units. RESULTS: At six-months follow-up, the whole study population had significant improvement in symptoms, systolic function, and QRS duration (P < 0.001); 32 (84%) patients had a favorable clinical outcome, 25 (66%) were considered responders according to the previous definition. Postimplant QRS was similarly reduced in both responders and nonresponders, whereas EDP had a significant improvement only in responders (P < 0.05). Using EDP, 23 (79%) patients were responders compared with 2 (22%) patients without mechanical dyssynchrony (P = 0.002). CONCLUSIONS: In HF patients with previous RV pacing, CRT is effective to improve clinical, functional outcome, and LV performance and to reduce electromechanical dyssynchrony in a large proportion of patients. Dyssynchrony evaluated by standard and TDI ECHO can be useful for CRT selection of paced patients. PMID- 17725753 TI - Patient evaluation of ICD recall communication strategies: a vignette study. AB - INTRODUCTION: Communication about the unprecedented number of implantable cardioverter defibrillator (ICD) recalls has proved challenging. While initial studies have explored the psychological impact of recalls on patients, the optimal way to communicate recalls is not currently known. This study investigated the way communication of a recall can affect patients' responses. METHODS: Sixty-six ICD patients read one of six vignettes that detailed a hypothetical device recall. Vignette variables included the source of recall dissemination (physician vs. media vs. device manufacturer) and the personal relevance (own brand is recalled vs. different brand is recalled). Subsequently, patients rated their agreement to 12 statements concerning their response to the recall on a scale from 1 (Strongly Disagree) to 5 (Strongly Agree). RESULTS: Patients were significantly more confident in the accuracy of recall information from both their physician and their manufacturer compared with the media, F (2, 63) = 36.10, P < 0.01, eta(2)= 0.53. Interestingly, patients were concerned about the recall regardless of whether their brand of ICD was recalled. Survey results indicated that 78.6% of patients reported learning about recalls from the media. In stark contrast, 77.0% of patients asserted preferring to learn about recalls from their physician. CONCLUSIONS: ICD patients report increased confidence in the accuracy of the recall information from physicians and manufacturers compared with the media in reporting recalls. Because it seems that most ICD patients learn about recalls from the media, these results demonstrate a disconnect between the initial source of recall information and the patients' desired sources. PMID- 17725754 TI - Hemodynamic collapse during left ventricular lead implantation. AB - Hypotension as a procedural complication during cardiac resynchronization therapy (CRT) implantation was reported in the initial randomized clinical trials. However, this phenomenon is not well characterized. We reviewed our CRT implantation experience to better understand this issue. There were 105 patients who underwent left ventricular lead implantation for CRT. Four patients had marked hypotension (systolic blood pressure < or = 50 mmHg) during the procedure. All had a history of hypertension and diabetes mellitus and were pacemaker dependent. Two had normal renal function, one had moderate renal insufficiency, and one was on dialysis. Three patients had ischemic cardiomyopathy. All had left ventricular ejection fraction < or =20% and were in New York Heart Association class III. Propofol and midazolam were used for sedation as standard protocol. Two patients had sudden hypotension when the coronary sinus was being cannulated, and two patients experienced sudden hypotension during left ventricular pacing. Cardiac tamponade as a possible cause was ruled out by echocardiography. We discuss possible mechanisms of sudden hemodynamic collapse during CRT implantation. PMID- 17725755 TI - An approach to ablate and pace:AV junction ablation and pacemaker implantation performed concurrently from the same venous access site. AB - BACKGROUND: Atrioventricular junction (AVJ) ablation combined with permanent pacemaker implantation (the "ablate and pace" approach) remains an acceptable alternative treatment strategy for symptomatic, drug-refractory atrial fibrillation (AF) with rapid ventricular response. This case series describes the feasibility and safety of catheter ablation of the AVJ via a superior vena caval approach performed during concurrent dual-chamber pacemaker implantation. METHODS: A total of 17 consecutive patients with symptomatic, drug-refractory, paroxysmal AF underwent combined AVJ ablation and dual-chamber pacemaker implantation procedure using a left axillary venous approach. Two separate introducer sheaths were placed into the axillary vein. The first sheath was used for implantation of the pacemaker ventricular lead, which was then connected to the pulse generator. Subsequently, a standard ablation catheter was introduced through the second axillary venous sheath and used for radiofrequency (RF) ablation of the AVJ. After successful ablation, the catheter was withdrawn and the pacemaker atrial lead was advanced through that same sheath and implanted in the right atrium. RESULTS: Catheter ablation of the AVJ was successfully achieved in all patients. The median number of RF applications required to achieve complete AV block was three (range 1-10). In one patient, AV conduction recovered within the first hour after completion of the procedure, and AVJ ablation was then performed using the conventional femoral venous approach. There were no procedural complications. CONCLUSION: Catheter ablation of the AVJ can be performed successfully and safely via a superior vena caval approach in patients undergoing concurrent dual-chamber pacemaker implantation. PMID- 17725756 TI - Evaluating patients with acute ischemic stroke with special reference to newly developed atrial fibrillation in cerebral embolism. AB - BACKGROUND: Cardioembolic strokes are extensive and have a poor prognosis. To identify the cardiovascular risk factors of cardioembolic stroke, we evaluated the cardiovascular status with special reference to persistent atrial fibrillation (AF) and paroxysmal atrial fibrillation (PAF) combined with the type of acute ischemic stroke. METHODS: We divided 315 consecutive patients admitted to our Department of Neurosurgery with an acute ischemic stroke into four types of brain infarction using clinical history, onset pattern of stroke, and brain imaging: cardioembolic (group E, n = 105), lacunar (group L, n = 92), atherothrombotic (group T, n = 111), and unclassified (n = 7). All patients underwent standard electrocardiography (ECG), a 24-hour ECG recording (Holter ECG) and transthoracic echocardiography (UCG). RESULTS: Persistent AF or PAF was detected in 97 patients (31.5%) using Holter ECG: more frequently in group E (67.6%) than in groups L (15.2%) or T (9.2%). Persistent AF or PAF was first diagnosed on admission using a standard ECG in 16 patients (5.2%) with no previous history and 14 of these patients belonged to group E (13.3%). PAF was newly detected on Holter ECG in another 26 patients (8.4%) and 13 of these patients (12.4%) belonged to group E. Concerning UCG, left atrial enlargement and mitral regurgitation were more frequent in group E than in group L or T. CONCLUSION: Holter ECG in addition to ECG on admission is important for detecting persistent AF or PAF in patients with ischemic stroke, especially with cardioembolism as diagnosed by neuroimaging. PMID- 17725757 TI - Cryoablation of accessory pathways in children. AB - BACKGROUND: Cryoablation is utilized for septal tachycardia substrates due its safety. Considering the recent studies which reveal coronary artery stenosis related to radiofrequency ablation (RFA) in children, cryoablation may offer advantages for nonseptal accessory pathways (APs) as well. The aim of this study was to investigate the efficacy and safety of cryoablation of APs in children. METHODS: A total of 39 patients (median age = 9.3 years, range 4.8 to 17.2 years) underwent cryoablation of APs. A three-dimensional, surface electrode-based navigation system (EnSite NavX, St. Jude Medical Inc., St. Paul, MN, USA) is used to decrease the fluoroscopy exposure. RESULTS: A total of 45 APs were identified. Of these APs, 23 were septal (anteroseptal, midseptal, posteroseptal) and 22 were nonseptal. Acute success rate with cryoablation was 73%. RFA was used when cryoablation failed and overall acute success rate was 84%. To assess for the effect of institutional experience, the initial 23 APs were compared to the recent 22 APs and acute success rate revealed significant improvement (57% vs. 91%). Recurrence rate was 24% during a median follow-up of 282 days. CONCLUSION: Cryoablation of APs is safe and yields to high acute success rates in children. It can potentially be used as the first ablation option for all APs in children. However, recurrence rate is higher compared to the RFA and there is a need for prospective comparative studies. PMID- 17725758 TI - Effect of dl-sotalol on mortality and recurrence of ventricular tachyarrhythmias: ischemic compared to nonischemic cardiomyopathy. AB - OBJECTIVE: We compared the effectiveness of sotalol on mortality and the recurrence of ventricular tachyarrhythmia (VTA) between idiopathic dilated cardiomyopathy (IDCM) and coronary artery disease (CAD). PATIENTS: Forty patients with spontaneous VTA and induced VTA associated with CAD (n = 23) and IDCM (n = 17) were studied. In all patients, sotalol was prescribed and an electrophysiologic study (EPS) was performed to evaluate its effect on the induction of VTA. There were no significant differences in left ventricular ejection fraction (LVEF) between CAD and IDCM (35%+/- 10% vs. 35%+/- 12%). RESULTS: After sotalol, there were no significant differences in the QTc interval on electrocardiogram (ECG) or in the effective refractory period in the apex of the right ventricle between the two groups, but sotalol was more effective in preventing the induction of VTA in CAD than in IDCM (65% vs. 29%; P < 0.05). During a mean follow-up period of 47 +/- 27 months, the overall VTA recurrence rate was significantly lower in CAD than in IDCM (P < 0.01). The all-cause mortality rate tended to be lower in CAD than in IDCM, but the difference was not significant (P = 0.07). Electrical storm (ES) occurred more frequently in IDCM than in CAD, (41% vs. 13%; P < 0.05), and all patients with ES (n = 10) failed to respond to sotalol as assessed by EPS. CONCLUSION: Sotalol reduced the overall VTA recurrence rate and all-cause mortality more in CAD than in IDCM. PMID- 17725759 TI - Unexpected, dramatic improvement in atrioventricular conduction during pacemaker implantation for apparent complete heart block. AB - We describe the case of a 29-year-old man with complete heart block after aortic and mitral valve surgery for bacterial endocarditis. Prior to pacemaker implantation, the patient had sinus bradycardia with third degree atrioventricular (AV) block. During testing of the atrial lead, the patient manifested intact AV conduction with a constant PR interval, which was robust up to 120 beats/min. This case represents a dramatic example of unexpected, improved AV conduction, perhaps a result of loss of Phase IV block. PMID- 17725760 TI - Shocking truths about implantable cardioverter defibrillator monitoring zones. AB - A 36 year-old man with hypertrophic cardiomyopathy and an ATLAS + DR implantable cardioverter defibrillator (ICD) (St. Jude Medical, Inc., St. Paul, MN, USA) for primary prevention received a shock while cycling. The ventricular fibrillation detection threshold was 182 beats/min. An additional monitoring zone was programmed to 156 beats/min with all discriminators "on" except morphology. On interrogation, the ICD shock followed sinus tachycardia. In the absence of a monitoring zone, device therapy would not have been expected. We explore the mechanisms by which monitoring zones could potentially contribute to inappropriate ICD therapy and offer trouble-shooting tips. PMID- 17725761 TI - A review of spinal injuries in the invasive cardiologist II: prevention and treatment. AB - This review provides a perspective of spinal injuries related to invasive cardiology, an understanding of the anatomy and physiology of the spine, the etiology and pathophysiology of spinal injuries, and options for prevention and treatment. In this part of our review, conventional surgical and minimally invasive options are discussed as well as emerging techniques for the treatment of back pain. We also discuss methods of preventing back injuries by modifications to the work environment as well as preventive measures that may be practiced by the invasive cardiologist. Our final objective is to describe and illustrate proven techniques for strengthening the supportive musculature to avoid spinal injury as well as to reduce painful exacerbations. PMID- 17725762 TI - Dexmedetomidine related cardiac arrest in a patient with permanent pacemaker; a cautionary tale. AB - Dexmedetomidine (Precedex), an alpha-2 adrenergic receptor agonist is frequently and safely used as sedative agent during surgical procedures. We report a case of a 76-year-old woman who developed cardiac arrest from the use of dexmedetomidine during pacemaker lead extraction procedure. PMID- 17725763 TI - Cardiac memory induced by QRS widening due to propafenone toxicity. AB - Propafenone toxicity can cause significant QRS widening and markedly abnormal ventricular activation pattern. Aberrant ventricular activation upon its resolution is known to produce persistent T-wave changes known as "cardiac memory" (CM). A 74-year-old woman presented with a severely abnormal electrocardiogram consistent with propafenone toxicity. As her QRS complex narrowed, T-wave inversions developed with the T-wave axis and resolution kinetics consistent with CM. Abnormal ventricular activation due to propafenone toxicity can result in CM development. PMID- 17725764 TI - Reverse remodeling with resynchronization in an asymptomatic patient with dilated hypokinetic cardiomyopathy. AB - Cardiac resynchronization therapy (CRT) is a validated treatment for selected heart failure patients who remain highly symptomatic despite optimal drug treatment. Yet there is currently no indication for CRT in patients with few or no symptoms. We report a spectacular "reverse remodeling" effect after CRT in an asymptomatic patient with hypokinetic dilated myocardiopathy who needed pacing for atrio-ventricular conduction disorder. CRT was chosen to prevent deterioration of left ventricular function by conventional right apical pacing. Thus, CRT could be indicated in patients with hypokinetic dilated myocardiopathy before the appearance of symptoms. PMID- 17725766 TI - A case of persistent atrial fibrillation cured by focal ablation in a young patient. AB - We present a case of a 25-year-old man who had persistent atrial fibrillation (AF) lasting for three months. The persistent AF was terminated by a 20-mg bolus infusion of adenosine triphosphate. Frequent and repetitive episodes of ectopic atrial tachycardia (EAT) emerged from the mid-portion of the saddle between the left superior and inferior pulmonary veins. The successful ablation was achieved by a focal ablation at the site with the earliest activation preceding the P-wave onset by 42 ms, and exhibited a QS pattern in the unipolar recording. This is rare case in which focal ablation could cure persistent AF. PMID- 17725765 TI - Challenges of diagnosis of long-QT syndrome in children. AB - We describe the clinical and genetic characteristics of the family, in which the diagnosis of LQT1 had been made. The electrocardiogram (ECG) characteristics of this patient indicated the likelihood of LQTS1. Polymorphic ventricular extrasystolies and episodes of polymorphic non-sustained ventricular tachycardia were confirmed by Holter ECG monitoring. On the exertional electrocardiogram polymorphic ventricular tachycardia (torsade de pointes) was recorded. Direct sequencing of both DNA strands revealed the absence of mutations or polymorphisms in the KCNQ1, HERG, and SCN5A genes. PMID- 17725767 TI - Cycle length dependent block in the "mitral-pulmonary vein" isthmus. AB - We report a case of cycle length dependent activation sequence in the coronary sinus catheter during assessment of mitral-pulmonary vein isthmus block. A 61 year-old patient presented with atrial tachycardia following a recent pulmonary vein isolation for paroxysmal atrial fibrillation. A perimitral macroreentrant atrial tachycardia was demonstrated during mapping. The isthmus block observed following initial ablation of the mitral-pulmonary vein appeared to be pacing cycle dependent and to our knowledge has not been previously described. PMID- 17725768 TI - How to determine chronaxie values of various electrodes? PMID- 17725770 TI - Cardiac resynchronization therapy in patients with heart failure and left bundle branch block. PMID- 17725771 TI - Evidence-based approaches to autism spectrum disorders. PMID- 17725773 TI - Stability and change in children with Developmental Coordination Disorder. AB - BACKGROUND: Children with Developmental Coordination Disorder (DCD) are a heterogeneous group who have a marked impairment in the performance of functional motor skills. Provision for these children is usually made via a paediatrician through occupational or physiotherapy; though with a prevalence rate of 5%, regular provision is rarely possible because of limited professional resources. METHODS: This study covers a period of nearly 4 years and initially examined a group of 31 children first identified as having DCD at 7-9 years of age. The children were observed and assessed before, during and after a total of 16 weeks of intervention carried out by parents and teachers. This was followed by a period of monitoring of performance for 26 of the children in the motor domain plus other abilities such as educational progress and self-concept. Individual children were tracked using a variety of qualitative and quantitative approaches, building up longitudinal whole child profiles. RESULTS: Following intervention, 14 of the 26 children have shown improvement and stability in all areas and no longer display DCD symptoms. Eight children have profiles which have shown variability, with the children moving in and out of the DCD classification, while the remaining four children have consistently scored poorly in their movement skills and in addition received ongoing support in school for academic subjects. CONCLUSIONS: The study has confirmed that children with DCD show varying profiles over a period of time and that the profiles have distinct characteristics related to events in the child's life. This approach to examining stability and change in the progressions of children's difficulties is in keeping with an ecological approach to explaining development with its multilayered influences creating changes. PMID- 17725775 TI - The impact of percutaneous endoscopic gastrostomy feeding in children; the parental perspective. AB - BACKGROUND: The prevalence of percutaneous endoscopic gastrostomy (PEG) feeding of children in the UK has increased. This study explored how gastrostomy feeding affects the daily lives of children and their families, from the parents' perspectives and developed a conceptual framework for assessing the impact of feeding on family life. METHODS: A semi-structured interview approach was used to obtain the parents' views regarding the impact of feeding on daily lives; both of the children and their family. The study was a cross-sectional qualitative design employing purposive sampling. Twenty-four interviews were conducted and data were analysed descriptively and thematically. RESULTS: Difficulties arising from PEG feeding included vomiting (71%), diarrhoea (33%), infection of the PEG site (46%) and leakage (54%). The key issues that emerged included delayed and disturbed sleep, restricted ability to go out, difficulties finding a place to feed, child care problems, negative attitudes of others towards feeding and family divisions. Parents primarily raised key issues regarding the impact of PEG feeding on themselves or the family rather than on the child. CONCLUSIONS: An assessment framework has been developed, based on the parents perceptions, for use in assessing the impact of feeding upon family life and identifying the support required for parents of children receiving PEG feeding. Provision of adequate support is likely to require a network of healthcare professionals, social care and support groups, all working together to meet identified needs. PMID- 17725774 TI - Health professionals' perceptions of feeding-related quality of life in children with quadriplegic cerebral palsy. AB - BACKGROUND: Our aim was to identify the major determinants of feeding-related quality of life (QoL) in children with quadriplegic cerebral palsy (QCP) from the perspective of health professionals to provide a framework for comprehensive clinical evaluation of health status in this group. METHODS: A trained facilitator conducted five semi-structured focus groups during September and November 2003. Participants were recruited through the two paediatric hospitals in Sydney and community-based services, and included general and specialist paediatricians (n = 18), nurses (n = 15) and allied health professionals (n = 13), with an 80% response rate. All sessions were audio- and videotaped. NVIVO software was used to facilitate thematic analysis of the transcribed audiotapes. RESULTS: Responses clustered into five themes: delivery of health services, parent-child interaction, the child's physical and emotional well-being, and social participation. Participants thought the QoL of child and parent was inseparable. Parent-child interaction, delivery of services and physical well being were the topics which prompted most participant interaction. These findings did not vary across disciplines. CONCLUSIONS: Health professionals identified five domains which provide a framework within which clinicians may comprehensively evaluate the health status of children with QCP and feeding difficulties. These five domains may also be used to inform a new feeding-related QoL instrument for use in this group of patients. PMID- 17725772 TI - Developmental Coordination Disorder and Joint Hypermobility Syndrome--overlapping disorders? Implications for research and clinical practice. AB - BACKGROUND: Joint Hypermobility Syndrome (JHS) and Developmental Coordination Disorder (DCD) are two childhood disorders usually identified separately. DCD is a heterogeneous condition with little known of the underlying aetiology of the disorder. This paper examines the potential overlap between DCD and JHS and examines children with DCD for symptoms which may be consistent with a diagnosis of JHS. Implications for research and clinical practice are considered. METHODS: A questionnaire covering a range of symptoms consistent with a diagnosis of JHS and related autonomic nervous systemic symptoms was completed by parents from 27 children with DCD and compared with responses from parents of 27 typically developing children. RESULTS: Children with DCD showed a significant difference from the group of typically developing children on questions regarding hypermobility, pain and autonomic nervous system symptoms, typifying JHS. CONCLUSIONS: This study has shown a similarity in symptoms seen in some DCD children to those with a diagnosis of JHS. In addition, children are also presenting with multi-system symptomatology including those involving the autonomic nervous system. This study reinforces other recent work showing the reverse pattern of JHS children showing similar functional similarities to DCD children. This has implications for future research in DCD in order to understand the underlying aetiology of this complex disorder. In addition, it is important for clinicians to be aware of these findings in order to provide appropriate and tailored support and treatment for children presenting with differing patterns of co-ordination difficulties. Children with DCD and JHS may require appropriate podiatry as well as recognition of their symptoms of pain and how this may affect participation in physical activity. PMID- 17725776 TI - Reliability of assessing the sensory perception of children with profound intellectual and multiple disabilities: a case study. AB - BACKGROUND: This study describes preliminary stages of developing a checklist to enable practitioners to determine the behavioural responses of children with profound intellectual and multiple disabilities to sensory stimuli. Reliability of currently used checklists is low, with a focus on the child's sensory integration instead of perception. METHODS: The inter-rater reliability of a checklist was determined, and adjustments were made to improve reliability. RESULTS: Strikingly, the reliability decreased for all components after adjustment. The effect of a smaller item pool was ruled out. The effect of familiarity of teachers as raters was examined. CONCLUSIONS: Results show that teachers who know a child well could interpret that child's behaviour more accurately than persons who were unfamiliar with the child. However, reliability of the checklist remains a problem. PMID- 17725777 TI - Abuse of the disabled child: a systematic review of population-based studies. AB - OBJECTIVE: To ascertain the strength of the association between childhood disability and abuse and neglect. METHODS: Systematic review of population-based studies published between 1966 and January 2006. Medline, Embase, Cinahl, Cochrane library, National Research Register, Social Sciences database and PsychInfo databases were searched for potentially relevant studies. INCLUSION CRITERIA: population-based cohort, case-control or cross-sectional studies of children <18 years of age that reported empirical data on the association of abuse with disability. Risk estimates were expressed as odds ratios with 95% confidence intervals (CI) where possible. Meta-analysis was not undertaken because of heterogeneity of studies. RESULTS: Four studies met the inclusion criteria. Two were longitudinal studies, one was a retrospective birth cohort and the remaining study was a cross-sectional survey. Types of disability studied varied widely as did methods used to ascertain abuse and neglect. Two studies accounted for potential confounding. Three studies reported an association between psychological and emotional disabilities and abuse. Two studies reported an association of learning disability with abuse. Only one study examined the association of physical disability (cerebral palsy) with abuse reporting an adjusted odds ratio for all forms of abuse of 1.79 (95% CI 0.96, 3.36) and for physical abuse of 3.00 (95% CI 1.29, 6.78). CONCLUSIONS: The evidence base for an association of disability with abuse and neglect is weak. Psychological and emotional problems, and learning difficulties appear to be associated with abuse but this association might arise because these conditions share a common aetiological pathway with abuse. There is limited evidence that physical disability predisposes to abuse. PMID- 17725778 TI - Development of the Oxford ankle foot questionnaire: finding out how children are affected by foot and ankle problems. AB - BACKGROUND: A large number of children are affected by foot and ankle problems owing to congenital deformities, clinical syndromes, neuromuscular conditions or trauma. This study aimed to identify how children's lives are affected by foot and ankle problems from the child's perspective as the first stage in developing a family-assessed instrument. METHODS: This was a qualitative study using focus groups involving children with a variety of foot and ankle problems aged 5-7, 8 11 and 12-15 years, and separate concurrent groups for their parents. The focus groups were child-centred and involved creative activities; there were two main exercises. The first activity involved agreeing or disagreeing with several statements about children with foot and ankle problems; the second activity explored a typical 'day in the life' of a child with a foot or ankle problem. All the groups were audio-recorded and transcribed; grounded theory and comparative content analysis were used to identify and code themes participants reported as important. RESULTS: The groups ran successfully with children in all ages. Consistent themes identified by all groups were; (i) specific activities that were more difficult; (ii) physical symptoms; (iii) reduced participation in certain life situations; and (iv) self-consciousness. There were few differences in the issues raised by each age group although the life situations children encounter tend to become more complex as they get older; there is also the difficulty of negotiating a larger school campus at senior compared with junior school. There were no differences in the issues raised by children and their parents. CONCLUSIONS: Focus groups involving creative child-centred activities were used successfully to elicit children's experience of their health problems. In addition to expected activity limitations and physical symptoms some children with foot or ankle problems endure participation restrictions and self consciousness that are exacerbated by the behaviour of other people or their environment, particularly at school. The findings of this study informed the development of a questionnaire to measure how severely children are affected by foot or ankle problems from the child's perspective. PMID- 17725779 TI - The provision of communication aids to children in England: an analysis of applications to the Communication Aids Project. AB - BACKGROUND: Children who experience difficulties in face-to-face interaction, understanding language and developing literacy can benefit from the provision of communication aids such as speech synthesizers and specialist software applications that support their social participation and learning. The Communication Aids Project (CAP) was a national initiative by the Department for Education and Skills in England, aimed at supporting and developing the provision of communication aids to children. This paper presents an analysis of the number and type of applications to CAP. In so doing, the paper begins to explore how the need for communication aids might be understood in England. METHODS: The analysis was carried out on a database of 3060 anonymized records, representing applications to CAP between January 2002 and January 2004. RESULTS: Applications to CAP were made on behalf of children with a broader range of disabilities than might be assumed, including a relatively high proportion of children with autistic spectrum disorder. Rates of application to CAP varied in line with Local Education Authority population size [e.g. total pupils, total pupils with special educational needs (SEN)], rather than indicators of regional variation in SEN provision (e.g. proportion of population identified as having SEN). CONCLUSIONS: Within a context of changing services to children in England and increasing emphasis on the plurality and contestability of services, the relevance of these findings for service providers and service commissioners is discussed. PMID- 17725780 TI - Involving families who have deaf children using a Family Needs Survey: a multi agency perspective. AB - BACKGROUND: Meeting the needs of deaf children and their families is multidisciplinary. Models of multi-agency working are diverse, and there is little evidence on outcome for family and child. Effective collaboration is an essential part of multi-agency working, and how this is achieved is an area that warrants research. METHODS: An approach was developed to identify family needs using a need identification tool called a Family Needs Survey (FNS) in conjunction with a multi-agency meeting. The FNS was introduced in a pilot study to involve parents of deaf children with services and to identify their needs from their perspective. RESULTS AND CONCLUSIONS: A clear pathway was determined for application of the FNS. A model of multi-agency working was developed that involves families directly with different services at one time. Outcomes were measured by uptake of the FNS, parental attendance at multi-agency meetings, and completion of a parent evaluation questionnaire. Discussion of the FNS at a multi agency meeting facilitates communication between professionals and between professionals and parents. There is some evidence that the FNS may be a useful tool. The majority of parents completed a FNS before multi-agency meetings and have indicated they are happy to share the information with other professionals. PMID- 17725781 TI - Parents' and service providers' perceptions of family-centred practice in a community-based, paediatric disability service in Australia. AB - BACKGROUND: For children who have physical disabilities and their families, involvement with a variety of providers of rehabilitation services is the norm rather than the exception. Despite family-centred practice (FCP) being recognized as the 'best practice' model, families experience models of service provision that range from 'expert' to 'collaborative'. After adopting FCP at Novita Children's Services in South Australia, it was imperative to determine the effectiveness of the implementation of FCP. Aim To investigate parents' and staff's perceptions of FCP at Novita as part of ongoing quality assurance activity, and to identify any gaps in the services provided. METHODS: The Measures of Processes of Care (MPOC) for parents/caregivers and service providers were utilized. A total of 189 families stratified by the three age groups of clients (<6, 6-12 and 13-18 years) and home location (metropolitan and rural) completed the MPOC-20 questionnaire. A total of 145 staff, allied health therapists, rehabilitation engineers, managers and other staff who have direct contact with clients and their families completed the MPOC - service providers (MPOC-SP) questionnaire. RESULTS: Parents generally rated the family-centred behaviours of staff as positive. Respectful and supportive care received the highest rating, while providing general information received the lowest. There were significant differences in scores for all five scales of the MPOC between metropolitan and rural families and the age of the child. Service providers also generally rated their family-centred behaviours as positive. There were significant differences among the professions in areas of showing interpersonal sensitivity and providing general information. CONCLUSIONS: The findings suggest that parents and service providers perceive FCP as positive at Novita, with some areas for improvement. The MPOC-20 and MPOC-SP can be used to measure FCP and to identify service delivery gaps, which warrant further exploration. PMID- 17725782 TI - Towards integrated paediatric services in the Netherlands: a survey of views and policies on collaboration in the care for children with cerebral palsy. AB - AIM: Worldwide, family-centred and co-ordinated care are seen as the two most desirable and effective methods of paediatric care delivery. This study outlines current views on how team collaboration comprising professionals in paediatric rehabilitation and special education and the parents of children with disabilities should be organized, and analyses the policies of five paediatric rehabilitation settings associated with the care of 44 children with cerebral palsy (CP) in the Netherlands. METHODS: For an overview of current ideas on collaboration, written statements of professional associations in Dutch paediatric rehabilitation were examined. The policy statements of the five participating settings were derived from their institutional files. Documents detailing the collaborative arrangements involving the various professionals and parents were evaluated at the institutional level and at the child level. Involvement of the stakeholders was analysed based on team conferences. RESULTS: Also in the Netherlands collaboration between rehabilitation and education professionals and parents is endorsed as the key principle in paediatric rehabilitation, with at its core the team conference in which the various priorities and goals are formulated and integrated into a personalized treatment plan. As to their collaborative approaches between rehabilitation centre and school, the five paediatric settings rarely differed, but at the child level approaches varied. Teams were large (averaging 10.5 members), and all three stakeholder groups were represented, but involvement differed per setting, as did the roles and contributions of the individual team members. CONCLUSION: Collaboration between rehabilitation and education professionals and parents is supported and encouraged nationwide. Views on collaboration have been formulated, and general guidelines on family-centred and co-ordinated care are available. Yet, collaborative practices in Dutch paediatric care are still developing. Protocols that carefully delineate the commitments to collaborate and that translate the policies into practical, detailed guidelines are needed, as they are a prerequisite for successful teamwork. PMID- 17725783 TI - One-year stability of the Measure of Processes of Care. AB - BACKGROUND: The Measure of Processes of Care (MPOC) is a 56-item self administered measure designed to examine what parents of a child with a chronic health problem think of the services they and their child receive, and to measure the extent to which these services are family-centred. Reliability and validity of the MPOC were established in prior studies. The aim of the present study was to assess the 1-year stability of the MPOC to justify its use as an evaluative tool. METHODS: Nine paediatric rehabilitation centres in the Netherlands participated in this short longitudinal survey study. Subjects were 205 parents (response rate 74.8%) of children aged 1-18 years who received care in one of the participating paediatric rehabilitation centres. All subjects filled out two MPOCs with a 1-year interval. RESULTS: All correlations between the scale scores of the MPOC at the first and second administration were relatively high and significant (range: 0.443-0.609, all P < 0.001), demonstrating high inter individual stability. However, all mean scale scores, except for Providing General Information, significantly reduced after 1 year. CONCLUSIONS: The MPOC has a moderate 1-year stability. However, because of its tendency to score lower when repeated after 1 year, its use as an evaluative follow-up instrument to assess the effectiveness of a programme intervention is restricted. PMID- 17725784 TI - The costs of key worker support for disabled children and their families. AB - BACKGROUND: Key workers provide a single point of contact for disabled children and their families, supporting them and facilitating access to other services. Key worker services appear to generate good outcomes for families and provision is encouraged through central government policy. Recent increases in key worker provision have been accompanied by a proliferation of delivery models yet there is very little information on their costs. METHODS: Within a study identifying which service characteristics generate good outcomes for families, unit costs for seven key worker services were estimated. Informed by economic theory, the estimates drew on data from managers, finance departments and other publicly available sources. Data on the frequency and duration of contact with key workers were obtained from families and combined with the service-specific unit costs to arrive at the contact cost per family. The variations in the costs of supporting families were explored. RESULTS: On average, key worker contact with disabled children and their families cost pound 151 over a 3-month period. Contact costs were found to vary with the level of the child's disability and the number of role aspects that key workers performed. This latter variable was associated with improved outcomes. CONCLUSION: The low response rate to the questionnaire and absence of data on the costs of other elements of the families' support packages may limit generalization from this study. Even so, such findings can help inform managers and planners about allocation of their scarce resources. Good-quality services appear to cost more but the relationship between cost, quality and outcomes is not a simple one. PMID- 17725785 TI - Providing a children's palliative care service in the community through fixed term grants: the staff perspective. AB - BACKGROUND: Children's palliative care services have recently been awarded fixed term grants, aimed at improving the provision of care for children with life limiting conditions in the community. We report findings of a qualitative study to investigate the experience of a cohort of community children's nurses from teams involved in setting up or extending community-based children's palliative care services. The purpose of the study was to identify factors that affect service delivery, from the staff perspective, and to suggest ways of promoting their sustainable development. METHODS: Semi-structured telephone interviews were conducted with 21 nurses from 12 different teams providing palliative care for children at home and in hospices. Participants were questioned about the services they provided and their own roles in that provision. NVIVO qualitative data analysis software was used to explore themes arising from the transcribed recorded interviews. FINDINGS: Key findings were the importance of physical location in facilitating multidisciplinary communication, the importance of defining role boundaries between existing and new providers of children's palliative care, and the potentially detrimental impact of insecure funding on referral patterns and recruitment to posts. Staff named the opportunity to offer direct 'hands-on' care to families, access to work-based support and networking opportunities as important factors in helping them cope with the stresses involved in managing finite resources and the emotional challenges of their work. CONCLUSIONS: The maintenance of a mixed caseload with a significant proportion of direct care, provision of ongoing support and clearly defined roles are recommended as means of bolstering the ability of staff to develop their services. The deliberate locating of services to enhance communication between staff and guidance on the preparation of funding applications may further contribute to the sustainability of these services. PMID- 17725786 TI - Paediatric SpRs' experiences of breaking bad news. AB - AIMS: To ascertain the level of support and training available to paediatric specialist registrars (SpRs) in breaking bad news and their self-reported confidence in this task. STUDY DESIGN: A questionnaire-based survey. PARTICIPANTS: Paediatric SpRs working in North Thames region. METHODS: Specialist registrars (n = 206) were sent a questionnaire relating to the level of support and training available to them in breaking bad news and their attitudes to this task. A repeat questionnaire was sent out 2 weeks later. RESULTS: The response rate was 54.9%. The study sample included 78 females and 34 males. The median year of qualification was 1995 [interquartile range (IQR) 1993-1997] and the median year of Calman training was Year 3 (IQR 2-4). Only 15.9% of participants had guidelines where they worked and 91.2% had received training in breaking bad news. Median self-perceived confidence in breaking bad news was rated as 4 out of 5. Only 21.2% of all respondents had both disclosed a diagnosis of Down syndrome and received feedback on their performance from their seniors. Few SpRs were able to adhere to all evidence-based recommendations for breaking bad news. DISCUSSION: Most SpRs had received training in breaking bad news and self reported confidence in this skill was high, although their hands-on experience was limited. Recent research shows, however, that parental dissatisfaction with the way in which bad news is broken remains high. The potential discrepancy between self-reported confidence and actual competence casts doubt on the value of self-evaluation. PMID- 17725787 TI - How much do junior staff know about common legal situations in paediatrics? AB - BACKGROUND: Recent high-profile medico-legal cases such as the death of Victoria Climbie and the subsequent Laming report have highlighted widespread deficiencies in child protection practice. Junior doctors are the frontline staff regularly facing issues with potentially major legal implications, including child protection, Gillick competence, consent, and professional responsibility/accountability. It is therefore important for them to be aware and understand the Children Act, common medico-legal principles and practices, particularly in the current, increasingly litigious climate. AIMS: (1) To determine junior medical staff's knowledge of legal issues involved in child protection and common basic legal situations, and (2) to assess whether experience and training improved this knowledge. METHODS: A standardized structured interview was developed exploring common issues with important legal implications for paediatric practice. It focused on: legal issues in child protection, the Children Act, awareness of the General Medical Council (GMC), principles of professional responsibility/accountability, the Bolam principle for good medical practice and Gillick competence. Basic demographic data were recorded. We attempted to contact all 180 paediatric junior medical staff in Wales by telephone. RESULTS: Interviews were conducted with 119/180 (66%) doctors: 46/56 specialist registrars (SpRs; 82%) and 73/124 senior house officers (SHOs; 59%). SpRs scored a median of 6.5 correct responses from a possible of 12 (range 3-11), compared with a median of 5 (range 1-11) by the SHOs (P < 0.0001; Mann-Whitney test). A third of SHOs and a fifth of SpRs were unaware that the GMC was the organization responsible for good medical practice in the UK. Similarly, a fifth of all juniors were ignorant of the legal age for consent. Approximately two-thirds of the SHOs and half of the SpRs were ignorant that the police and social services have the legal power to protect the child in child protection cases. Alarmingly, none of the SHOs and only 11% of the SpRs were aware of the Bolam principle. SpRs scored significantly higher on topics of Gillick competence, legal right to see medical notes, consent, Children Act, burden of proof in civil and criminal court, and on Bolam principle. They also had received training more frequently than SHOs, which, when combined with their greater experience, probably explains these statistically significant differences. CONCLUSION: Few junior staff have adequate knowledge of the basic legal principles and practice as they relate to children. Widespread deficiencies concerning the understanding of the Children Act and child protection powers exist. PMID- 17725788 TI - The importance of size and growth in infancy: integrated findings from systematic reviews of scientific evidence and lay perspectives. AB - BACKGROUND: Associations between growth and size during infancy and adult disease have led some to recommend that interventions in infancy might benefit lifelong health. Any such recommendations should be informed by both the scientific evidence for relationships between infancy and later outcomes and the views and opinions of those who care for babies. METHODS: Separate, but interlinked, systematic reviews were conducted of the epidemiological evidence relating infant size or growth to later health and of lay perspectives on infant size and growth. Findings were compared and integrated to consider policy implications. RESULTS: Lay and scientific perspectives both cast infant growth and size as an indicator of other aspects of an infant's life, rather than being of fundamental importance. While the scientific literature is most often concerned with infants at the extreme ends of the population distribution, and towards long-term outcomes, the literature on lay perspectives suggests a focus on defining the 'normal' range, and on current health. CONCLUSIONS: Differences and similarities between scientific and lay perspectives on health can highlight areas of agreement, as well as areas of potential misunderstanding or miscommunication. PMID- 17725789 TI - The effects of a 3-year obesity intervention in schoolchildren in Beijing. AB - BACKGROUND: Childhood obesity has become a health problem in urban areas in China. Intervention to reduce childhood obesity should be of high priority. School-based intervention programmes are needed to deal with the growing prevalence of childhood obesity in China. METHODS: Five primary schools were selected randomly for this study in the Beijing urban area in China; two were allocated to the intervention group and three to the control group. A total of 2425 children (1029 children in intervention schools and 1396 children in control schools) took part in the study for 3 years. In the intervention group, children and their parents were involved in a programme of nutrition education and physical activity. Control school students followed their usual health and physical education curriculum with no extra intervention. RESULTS: After the 3 year intervention, the prevalence of overweight and obesity were significantly lower in the intervention schools than in the control schools (overweight: 9.8% vs. 14.4%, P < 0.01; obesity: 7.9% vs. 13.3%, P < 0.01). The prevalence of overweight and obesity decreased by 26.3% and 32.5% in intervention schools respectively after intervention. The prevalence of overweight and obesity increased in control schools. There was also significant difference in body mass index between intervention and control schools (18.2 +/- 2.6 vs. 20.3 +/- 3.4, P < 0.01) after intervention. More non-obese children became obese in the control schools (7.0%) than in the intervention schools (2.4%) at end line (P < 0.01). Among the children who were obese at baseline, 49.2% remained obese at end line in intervention schools while 61.9% remained obese in control schools (P < 0.01). CONCLUSIONS: Our study showed that an intervention programme could be feasible in schools in Beijing, China. The prevalence of overweight and obesity was reduced in schoolchildren in Beijing through an intervention focused on nutrition education and physical activity. Overweight and obesity children as well as normal weight children and their parents should be involved in such an intervention programme. PMID- 17725799 TI - Aedes Dronc: a novel ecdysone-inducible caspase in the yellow fever mosquito, Aedes aegypti. AB - Caspases are cysteinyl-aspartate-specific proteases known for their role in apoptosis. Here, we describe the characterization of Aedes Dronc, a novel caspase in the yellow fever mosquito, Aedes aegypti. Aedes Dronc is predicted to contain an N-terminal caspase recruitment domain and is a homologue of Drosophila Dronc and human caspase-9. An increase in transcripts and caspase activity coincides with developmental changes in the mosquito, suggesting that Aedes Dronc plays a role in developmental apoptosis. Exposure of third instar larvae to ecdysone resulted in a significant increase in both transcript levels and caspase activity. We present here a functional characterization of the first caspase recruitment domain-containing caspase in mosquitoes, and will initiate studies on the role of apoptosis in the innate immune response of vectors. PMID- 17725800 TI - A novel cadherin-like gene from western corn rootworm, Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae), larval midgut tissue. AB - A cadherin-like gene associated with larval midgut tissues was cloned from western corn rootworm (Diabrotica virgifera virgifera: Coleoptera), an economically important agricultural pest in North America and Europe and the primary target pest species for corn hybrids expressing Cry3 toxins from Bacillus thuringiensis (Bt). The full-length cDNA (5371 bp in length) encodes an open reading frame for a 1688 amino acid polypeptide. The putative protein has similar architecture to cadherin-like proteins isolated from lepidopteran midguts that have been shown to bind to Cry1 Bt toxins and have been implicated in Bt resistance. The D. v. virgifera cadherin-like gene is expressed primarily in the larval midgut and regulated during development, with high levels of expression observed in all instars and adults but not pupae. The corresponding genomic sequence spans more than 90 kb and is interspersed with 30 large introns. The genomic organization of the cadherin-like gene for this coleopteran species bears strong resemblance to lepidopteran cadherins suggesting a common molecular basis for susceptibility to Cry3 toxins in Coleoptera. PMID- 17725801 TI - Changes in Drosophila melanogaster midgut proteins in response to dietary Bowman Birk inhibitor. AB - The midgut proteome of Drosophila melanogaster was compared in larvae fed dietary Bowman-Birk inhibitor (BBI) vs. larvae fed a control diet. By using two dimensional gel electrophoresis, nine differentially expressed proteins were observed, which were associated with enzymes or transport functions such as sterol carrier protein X (SCPX), ubiquitin-conjugating enzyme, endopeptidase, receptor signalling protein kinase, ATP-dependent RNA helicase and alpha tocopherol transport. Quantitative real-time PCR verified differential expression of transcripts coding for six of the proteins observed from the proteomic analysis. BBI evidently affects expression of proteins associated with protein degradation, transport and fatty acid catabolism. We then tested the hypothesis that SCPX was critical for the Drosophila third instars' response to BBI treatment. Inhibition of SCPX caused the third instars to become more susceptible to dietary BBI. PMID- 17725803 TI - A positive Donath-Landsteiner test in paroxysmal cold haemoglobinuria. PMID- 17725802 TI - Rituximab responsive immune thrombocytopenic purpura in an adult with underlying autoimmune lymphoproliferative syndrome due to a splice-site mutation (IVS7+2 T>C) affecting the Fas gene. AB - A 36 yr-old man of Israeli descent with a history of childhood splenectomy for severe thrombocytopenia and a family history of autoimmune lymphoproliferative syndrome (ALPS), presented with severe immune thrombocytopenic purpura refractory to standard therapy. He was found to possess a heterozygous mutation in the Fas gene (also termed TNFRSF6, CD95, Apo-1) affecting the donor splice site of intron 7 (IVS7+2 T>C). This frameshift mutation truncates the cytoplasmic domain of the Fas death receptor, resulting in circulating CD4/8 double negative T lymphocytes, lymphadenopathy and autoimmune complications typical of ALPS. Administration of Rituximab in this patient was associated with a durable hematologic response (currently more than 12 months). This report highlights the need to consider rare inherited causes of thrombocytopenia in adults with a family history of immune cytopenia(s) and the effective use of anti-CD20 monoclonal antibody in patients unresponsive to immunosuppression and splenectomy. PMID- 17725804 TI - Up-regulation of CD147 and matrix metalloproteinase-2, -9 induced by P glycoprotein substrates in multidrug resistant breast cancer cells. AB - Treatment of animals bearing multidrug resistant (MDR) tumor cells with P glycoprotein (P-gp) substrates could worsen host survival. It is assumed that this is due to increased tumor metastasis. To clarify the mechanism(s) underlying this observation, the MDR human breast cancer cell line, MCF-7/AdrR, and its sensitive parental line, MCF-7, was treated with various concentrations of P-gp substrate drugs (vincristine, paclitoxel, adriamycin) and a P-gp non-substrate drug (bleomycin) in serum-free media. Increased production of CD147, and matrix metalloproteinases (MMP)-2, -9 was observed only in MDR cancer cells exposed to P gp substrates, as determined using real-time polymerase chain reaction, western blotting and zymography. Correspondingly, P-gp substrates significantly enhanced the in vitro invasion abilities of MCF-7/Adr cells. It was also found that the drug-induced promotion of CD147, and MMP-2, -9 was consistent with increased expression of epidermal growth factor receptor (EGFR) and that inhibition of either EGFR or P-gp activity could significantly interrupt the downstream effects, and so inhibit in vitro invasion abilities motivated by P-gp substrates. These results imply that treatment of MDR tumors with P-gp substrates could adversely affect therapeutic outcomes through modulating the production of CD147, MMP-2, -9, and EGFR, and suggest that this effect may be initiated by the transporter function of P-gp. PMID- 17725805 TI - Recklessness as a hallmark of aggressive cancer. AB - Cancer recurrence after surgical treatment is a major concern for patients and doctors. Understanding what makes tumors prone to recurrence would be an important step toward its prevention. Accumulating evidence indicates that the level of membrane-associated protease regulator reversion-inducing cysteine-rich protein with Kazal motifs (RECK) expressed in tumor tissue is a good prognostic indicator in several common cancers. Certain members of the matrix metalloproteinase family are often upregulated in advanced cancers and are known to play important roles in tumor angiogenesis, invasion and metastasis. RECK negatively regulates several matrix metalloproteinases. Therefore, RECK itself may well be considered a promising tool or target molecule to be activated in cancer therapy. Here we review the recent advances in RECK research and discuss some of the important issues to be addressed in future studies. PMID- 17725806 TI - Lack and restoration of sensitivity of lung cancer cells to cellular attack with special reference to expression of human leukocyte antigen class I and/or major histocompatibility complex class I chain related molecules A/B. AB - Both cytotoxic T lymphocytes (CTL) and natural killer (NK) cells may play major roles in the host defense against cancer. However, their relationship against the same tumor remains to be elucidated. Among 26 human lung cancer cell lines established in our laboratory, 10 (38%) exhibited human leukocyte antigen (HLA) class I haplotype loss and three (12%) lost HLA-class I expression totally by flow cytometry analysis. The two cell lines (E522L and C831L) that lost their expression of HLA-class I in vitro and in vivo were applied for further evaluations. Genetic abnormalities of beta2-microglobulin gene were observed in both E522L (loss of mRNA) and C831L (point mutation). Transduction of the wild type beta2-microglobulin gene rendered them positive for HLA-class I expression. The CTL were induced from autologous peripheral blood mononuclear cells or regional lymph node lymphocytes by stimulation with wild-type beta2-microglobulin transduced-E522L or -C831L, and they showed tumor-specific cytotoxicity against wild-type beta2-microglobulin-transductant, but not parental cells. In NK cell cytotoxicity, E522L showed high sensitivity to NK cells; however, C831L showed resistance despite loss of HLA-class I expression. E522L expressed MHC class I chain related molecules A/B, but C831L did not. The transduction of the MHC class I chain related molecule A gene from E522L rendered C831L positive for expression and sensitive to NK cell cytotoxicity. Reconstruction of HLA-class I and MHC class I chain related molecules A expression could abrogate evasion from cellular attack by CTL and NK cells, and it may lead to a breakthrough in the development of cancer immunotherapy. PMID- 17725807 TI - Prospective cohort study of body mass index in adolescence and death from stomach cancer in Japan. AB - We investigated the association between body mass index (BMI) values and the risk of death from stomach cancer later in life. From 1992 to 2000, 28 443 participants (13 211 men and 15 232 women) were followed, and 129 deaths from stomach cancer (86 men and 43 women) occurred. BMI (BMI at the baseline) and BMI(20y) (BMI at age 20 years) were obtained by questionnaire at the beginning of the study. Men in the middle and highest tertiles of BMI(20y) had a higher risk of death from stomach cancer than those in the lowest tertile (after controlling for covariates, hazard ratio [HR] = 2.73 with 95% confidence interval [CI] 1.26 5.89 for the middle tertile; HR = 2.15 with 95% CI 0.97-4.73 for the highest tertile), although there was no significant trend (P = 0.30). Likewise, women in the middle and highest tertiles of BMI(20y) had an increased risk of death from stomach cancer (HR = 5.17 with 95% CI 1.50-17.87 for the middle tertile; HR = 4.22 with 95% CI 1.18-15.05 for the highest tertile; P for trend = 0.05). The analysis of BMI at the baseline did not show a significant relationship with the risk of death from stomach cancer. These results suggest that a high BMI(20y) is associated with an increased risk of death from stomach cancer. PMID- 17725808 TI - A two-part joint model for the analysis of survival and longitudinal binary data with excess zeros. AB - Many longitudinal studies generate both the time to some event of interest and repeated measures data. This article is motivated by a study on patients with a renal allograft, in which interest lies in the association between longitudinal proteinuria (a dichotomous variable) measurements and the time to renal graft failure. An interesting feature of the sample at hand is that nearly half of the patients were never tested positive for proteinuria (>/=1g/day) during follow-up, which introduces a degenerate part in the random-effects density for the longitudinal process. In this article we propose a two-part shared parameter model framework that effectively takes this feature into account, and we investigate sensitivity to the various dependence structures used to describe the association between the longitudinal measurements of proteinuria and the time to renal graft failure. PMID- 17725809 TI - Mortality modeling of early detection programs. AB - Consider a group of subjects who are offered an opportunity to receive a sequence of periodic special examinations for the purpose of diagnosing a chronic disease earlier relative to usual care. The mortality for the early detection group is to be compared with a group receiving usual care. Benefit is reflected in a potential reduction in mortality. This article develops a general probability model that can be used to predict cumulative mortality for each of these groups. The elements of the model assume (i) a four-state progressive disease model in which a subject may be in a disease-free state (or a disease state that cannot be detected), preclinical disease state (capable of being diagnosed by a special exam), clinical state (diagnosis by usual care), and a death state; (ii) age dependent transitions into the states; (iii) age-dependent examination sensitivity; (iv) age-dependent sojourn time in each state; and (v) the distribution of disease stages on diagnosis conditional on modality of detection. The model may be used to (i) compare mortality rates for different screening schedules; (ii) explore potential benefit of subpopulations; and (iii) compare relative reductions in disease-specific mortality due to advances and dissemination of both treatment and early detection screening programs. PMID- 17725811 TI - Modeling individual effects in the Cormack-Jolly-Seber model: a state-space formulation. AB - In population and evolutionary biology, there exists considerable interest in individual heterogeneity in parameters of demographic models for open populations. However, flexible and practical solutions to the development of such models have proven to be elusive. In this article, I provide a state-space formulation of open population capture-recapture models with individual effects. The state-space formulation provides a generic and flexible framework for modeling and inference in models with individual effects, and it yields a practical means of estimation in these complex problems via contemporary methods of Markov chain Monte Carlo. A straightforward implementation can be achieved in the software package WinBUGS. I provide an analysis of a simple model with constant parameter detection and survival probability parameters. A second example is based on data from a 7-year study of European dippers, in which a model with year and individual effects is fitted. PMID- 17725810 TI - Aberrant crypt foci and semiparametric modeling of correlated binary data. AB - Motivated by the spatial modeling of aberrant crypt foci (ACF) in colon carcinogenesis, we consider binary data with probabilities modeled as the sum of a nonparametric mean plus a latent Gaussian spatial process that accounts for short-range dependencies. The mean is modeled in a general way using regression splines. The mean function can be viewed as a fixed effect and is estimated with a penalty for regularization. With the latent process viewed as another random effect, the model becomes a generalized linear mixed model. In our motivating data set and other applications, the sample size is too large to easily accommodate maximum likelihood or restricted maximum likelihood estimation (REML), so pairwise likelihood, a special case of composite likelihood, is used instead. We develop an asymptotic theory for models that are sufficiently general to be used in a wide variety of applications, including, but not limited to, the problem that motivated this work. The splines have penalty parameters that must converge to zero asymptotically: we derive theory for this along with a data driven method for selecting the penalty parameter, a method that is shown in simulations to improve greatly upon standard devices, such as likelihood crossvalidation. Finally, we apply the methods to the data from our experiment ACF. We discover an unexpected location for peak formation of ACF. PMID- 17725812 TI - Semiparametric approaches for joint modeling of longitudinal and survival data with time-varying coefficients. AB - We study joint modeling of survival and longitudinal data. There are two regression models of interest. The primary model is for survival outcomes, which are assumed to follow a time-varying coefficient proportional hazards model. The second model is for longitudinal data, which are assumed to follow a random effects model. Based on the trajectory of a subject's longitudinal data, some covariates in the survival model are functions of the unobserved random effects. Estimated random effects are generally different from the unobserved random effects and hence this leads to covariate measurement error. To deal with covariate measurement error, we propose a local corrected score estimator and a local conditional score estimator. Both approaches are semiparametric methods in the sense that there is no distributional assumption needed for the underlying true covariates. The estimators are shown to be consistent and asymptotically normal. However, simulation studies indicate that the conditional score estimator outperforms the corrected score estimator for finite samples, especially in the case of relatively large measurement error. The approaches are demonstrated by an application to data from an HIV clinical trial. PMID- 17725814 TI - Uniparental (mtDNA, Y-chromosome) polymorphisms in French Guiana and two related populations--implications for the region's colonization. AB - Blood samples collected in four Amerindian French Guiana populations (Palikur, Emerillon, Wayampi and Kali'na) in the early 1980s were screened for selected mtDNA and Y-chromosome length polymorphisms, and sequenced for the mtDNA hypervariable segment I (HVS-I). In addition, two other Amerindian populations (Apalai and Matsiguenga) were examined for the same markers to establish the genetic relationships in the area. Strong dissimilarities were observed in the distribution of the founding Amerindian haplogroups, and significant p-values were obtained from F(ST) genetic distances. Interpopulation similarities occurred mainly due to geography. The Palikur did not show obvious genetic similarity to the Matsiguenga, who speak the same language and live in a region from where they could have migrated to French Guiana. The African-origin admixture observed in the Kali'na probably derives from historical contacts they had with the Bushinengue (Noir Marron), a group of escaped slaves who now lead independent lives in a nearby region. This analysis has identified significant clues about the Amerindian peopling of the North-East Amazonian region. PMID- 17725815 TI - The temporal program of peripheral blood gene expression in the response of nonhuman primates to Ebola hemorrhagic fever. AB - BACKGROUND: Infection with Ebola virus (EBOV) causes a fulminant and often fatal hemorrhagic fever. In order to improve our understanding of EBOV pathogenesis and EBOV-host interactions, we examined the molecular features of EBOV infection in vivo. RESULTS: Using high-density cDNA microarrays, we analyzed genome-wide host expression patterns in sequential blood samples from nonhuman primates infected with EBOV. The temporal program of gene expression was strikingly similar between animals. Of particular interest were features of the data that reflect the interferon response, cytokine signaling, and apoptosis. Transcript levels for tumor necrosis factor-alpha converting enzyme (TACE)/alpha-disintegrin and metalloproteinase (ADAM)-17 increased during days 4 to 6 after infection. In addition, the serum concentration of cleaved Ebola glycoprotein (GP2 delta) was elevated in late-stage EBOV infected animals. Of note, we were able to detect changes in gene expression of more than 300 genes before symptoms appeared. CONCLUSION: These results provide the first genome-wide ex vivo analysis of the host response to systemic filovirus infection and disease. These data may elucidate mechanisms of viral pathogenesis and host defense, and may suggest targets for diagnostic and therapeutic development. PMID- 17725817 TI - Decrease in oxidative phosphorylation yield in presence of butyrate in perfused liver isolated from fed rats. AB - BACKGROUND: Butyrate is the main nutrient for the colonocytes but the effect of the fraction reaching the liver is not totally known. A decrease in tissue ATP content and increase in respiration was previously demonstrated when livers were perfused with short-chain fatty acids (SCFA) such as butyrate, or octanoate. In fed rats the oxidative phosphorylation yield was determined on the whole isolated liver perfused with butyrate in comparison with acetate and octoanoate (3 mmol/L). The rate of ATP synthesis was determined in the steady state by monitoring the rate of ATP loss after inhibition of (i) cytochrome oxidase (oxidative phosphorylation) with KCN (2.5 mmol/L) and (ii) glyceraldehyde 3 phosphate dehydrogenase (glycolysis) with IAA (0.5 mmol/L). The ATP flux, estimated by 31P Nuclear Magnetic Resonance, and the measured liver respiration allowed the ATP/O ratio to be determined. RESULTS: ATP turnover was significantly lower in the presence of butyrate (0.40 +/- 0.10 micromoles/min.g, p = 0.001, n = 7) and octanoate (0.56 +/- 0.10 micromoles/min.g, p = 0.01, n = 5) than in control (1.09 +/- 0.13 micromoles/min.g, n = 7), whereas perfusion with acetate induced no significant decrease (0.76 +/- 0.10 micromoles/min.g, n = 7). Mitochondrial oxygen consumption was unchanged in the presence of acetate (1.92 +/- 0.16 vs 1.86 +/- 0.16 for control) and significantly increased in the presence of butyrate (p = 0.02) and octanoate (p = 0.0004) (2.54 +/- 0.18 and 3.04 +/- 0.15 micromoles/min.g, respectively). The oxidative phosphorylation yield (ATP/O ratio) calculated in the whole liver was significantly lower with butyrate (0.07 +/- 0.02, p = 0.0006) and octanoate (0.09 +/- 0.02, p = 0.005) than in control (0.30 +/- 0.05), whereas there was no significant change with acetate (0.20 +/- 0.02). CONCLUSION: Butyrate or octanoate decrease rather than increase the rate of ATP synthesis, resulting in a decrease in the apparent ATP/O ratio. Butyrate as a nutrient has the same effect as longer chain FA. An effect on the hepatic metabolism should be taken into account when large quantities of SCFA are directly used or obtained during therapeutic or nutritional strategies. PMID- 17725818 TI - Experimental transmission of atypical scrapie to sheep. AB - BACKGROUND: Active surveillance for transmissible spongiform encephalopathies in small ruminants has been an EU regulatory requirement since 2002. A number of European countries have subsequently reported cases of atypical scrapie, similar to previously published cases from Norway, which have pathological and molecular features distinct from classical scrapie. Most cases have occurred singly in flocks, associated with genotypes considered to be more resistant to classical disease. Experimental transmissibility of such isolates has been reported in certain ovinised transgenic mice, but has not previously been reported in the natural host. Information on the transmissibility of this agent is vital to ensuring that disease control measures are effective and proportionate. RESULTS: This report presents the successful experimental transmission, in 378 days, of atypical scrapie to a recipient sheep of homologous genotype with preservation of the pathological and molecular characteristics of the donor. This isolate also transmitted to ovinised transgenic mice (Tg338) with a murine phenotype indistinguishable from that of Nor 98. CONCLUSION: This result strengthens the opinion that these cases result from a distinct strain of scrapie agent, which is potentially transmissible in the natural host under field conditions. PMID- 17725816 TI - Thioredoxin reductase is a key factor in the oxidative stress response of Lactobacillus plantarum WCFS1. AB - BACKGROUND: Thioredoxin (TRX) is a powerful disulfide oxido-reductase that catalyzes a wide spectrum of redox reactions in the cell. The aim of this study is to elucidate the role of the TRX system in the oxidative stress response in Lactobacillus plantarum WCFS1. RESULTS: We have identified the trxB1-encoded thioredoxin reductase (TR) as a key enzyme in the oxidative stress response of Lactobacillus plantarum WCFS1.Overexpression of the trxB1 gene resulted in a 3 fold higher TR activity in comparison to the wild-type strain. Subsequently, higher TR activity was associated with an increased resistance towards oxidative stress. We further determined the global transcriptional response to hydrogen peroxide stress in the trxB1-overexpression and wild-type strains grown in continuous cultures. Hydrogen peroxide stress and overproduction of TR collectively resulted in the up-regulation of 267 genes. Additionally, gene expression profiling showed significant differential expression of 27 genes in the trxB1-overexpression strain. Over expression of trxB1 was found to activate genes associated with DNA repair and stress mechanisms as well as genes associated with the activity of biosynthetic pathways for purine and sulfur containing amino acids. A total of 16 genes showed a response to both TR overproduction and hydrogen peroxide stress. These genes are involved in the purine metabolism, energy metabolism (gapB) as well as in stress-response (groEL, npr2), and manganese transport (mntH2). CONCLUSION: Based on our findings we propose that overproduction of the trxB1-encoded TR in L. plantarum improves tolerance towards oxidative stress. This response coincides with simultaneous induction of a group of 16 transcripts of genes. Within this group of genes, most are associated with oxidative stress response. The obtained crossover between datasets may explain the phenotype of the trxB1-overexpression strain, which appears to be prepared for encountering oxidative stress. This latter property can be used for engineering robustness towards oxidative stress in industrial strains of L. plantarum. PMID- 17725819 TI - Dimerization of inositol monophosphatase Mycobacterium tuberculosis SuhB is not constitutive, but induced by binding of the activator Mg2+. AB - BACKGROUND: The cell wall of Mycobacterium tuberculosis contains a wide range of phosphatidyl inositol-based glycolipids that play critical structural roles and, in part, govern pathogen-host interactions. Synthesis of phosphatidyl inositol is dependent on free myo-inositol, generated through dephosphorylation of myo inositol-1-phosphate by inositol monophosphatase (IMPase). Human IMPase, the putative target of lithium therapy, has been studied extensively, but the function of four IMPase-like genes in M. tuberculosis is unclear. RESULTS: We determined the crystal structure, to 2.6 A resolution, of the IMPase M. tuberculosis SuhB in the apo form, and analysed self-assembly by analytical ultracentrifugation. Contrary to the paradigm of constitutive dimerization of IMPases, SuhB is predominantly monomeric in the absence of the physiological activator Mg2+, in spite of a conserved fold and apparent dimerization in the crystal. However, Mg2+ concentrations that result in enzymatic activation of SuhB decisively promote dimerization, with the inhibitor Li+ amplifying the effect of Mg2+, but failing to induce dimerization on its own. CONCLUSION: The correlation of Mg2+-driven enzymatic activity with dimerization suggests that catalytic activity is linked to the dimer form. Current models of lithium inhibition of IMPases posit that Li+ competes for one of three catalytic Mg2+ sites in the active site, stabilized by a mobile loop at the dimer interface. Our data suggest that Mg2+/Li+-induced ordering of this loop may promote dimerization by expanding the dimer interface of SuhB. The dynamic nature of the monomer-dimer equilibrium may also explain the extended concentration range over which Mg2+ maintains SuhB activity. PMID- 17725821 TI - MaxAlign: maximizing usable data in an alignment. AB - BACKGROUND: The presence of gaps in an alignment of nucleotide or protein sequences is often an inconvenience for bioinformatical studies. In phylogenetic and other analyses, for instance, gapped columns are often discarded entirely from the alignment. RESULTS: MaxAlign is a program that optimizes the alignment prior to such analyses. Specifically, it maximizes the number of nucleotide (or amino acid) symbols that are present in gap-free columns - the alignment area - by selecting the optimal subset of sequences to exclude from the alignment. MaxAlign can be used prior to phylogenetic and bioinformatical analyses as well as in other situations where this form of alignment improvement is useful. In this work we test MaxAlign's performance in these tasks and compare the accuracy of phylogenetic estimates including and excluding gapped columns from the analysis, with and without processing with MaxAlign. In this paper we also introduce a new simple measure of tree similarity, Normalized Symmetric Similarity (NSS) that we consider useful for comparing tree topologies. CONCLUSION: We demonstrate how MaxAlign is helpful in detecting misaligned or defective sequences without requiring manual inspection. We also show that it is not advisable to exclude gapped columns from phylogenetic analyses unless MaxAlign is used first. Finally, we find that the sequences removed by MaxAlign from an alignment tend to be those that would otherwise be associated with low phylogenetic accuracy, and that the presence of gaps in any given sequence does not seem to disturb the phylogenetic estimates of other sequences. The MaxAlign web-server is freely available online at http://www.cbs.dtu.dk/services/MaxAlign where supplementary information can also be found. The program is also freely available as a Perl stand-alone package. PMID- 17725820 TI - Usefulness of open lung biopsy in mechanically ventilated patients with undiagnosed diffuse pulmonary infiltrates: influence of comorbidities and organ dysfunction. AB - BACKGROUND: The purpose of this study was to evaluate the clinical usefulness of open lung biopsy (OLB) in patients undergoing mechanical ventilation for diffuse pulmonary infiltrates of unknown etiology. METHODS: This was a 10-year retrospective study in a 10-bed medical intensive care unit. The medical records of 36 ventilator-dependent patients who underwent OLB for the diagnosis of unknown pulmonary infiltrates from 1994 to 2004 were reviewed retrospectively. Data analyzed included demographic data, Charlson age-comorbidity score, number of organ dysfunctions, Acute Physiology and Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) II, Sequential Organ Failure Assessment (SOFA) score, ventilation variables, and radiological patterns. Diagnostic yield, effect on subsequent treatment changes, and complications of OLB were also assessed. RESULTS: A specific clinico-pathologic diagnosis was obtained for 31 patients (86%). The most common diagnoses were interstitial pneumonia (n = 17, including 8 acute interstitial pneumonia) and viral pneumonia (n = 4). Therapeutic modifications were made in 64% of patients. Patients who received OLB less than 1 week after initiation of mechanical ventilation were more likely to survive (63% versus 11%; P = 0.018). There were no major complications associated with the procedure. Factors independently associated with survival were the Charlson age-comorbidity score, number of organ dysfunction and the PaO2/FiO2 ratio on the day of the OLB. CONCLUSION: OLB can provide a specific diagnosis in many ventilator-dependent patients with undiagnosed pulmonary infiltrate. Early OLB seems to be useful in critically ill patients with isolated respiratory failure. PMID- 17725822 TI - Exonization of the LTR transposable elements in human genome. AB - BACKGROUND: Retrotransposons have been shown to contribute to evolution of both structure and regulation of protein coding genes. It has been postulated that the primary mechanism by which retrotransposons contribute to structural gene evolution is through insertion into an intron or a gene flanking region, and subsequent incorporation into an exon. RESULTS: We found that Long Terminal Repeat (LTR) retrotransposons are associated with 1,057 human genes (5.8%). In 256 cases LTR retrotransposons were observed in protein-coding regions, while 50 distinct protein coding exons in 45 genes were comprised exclusively of LTR RetroTransposon Sequence (LRTS). We go on to reconstruct the evolutionary history of an alternatively spliced exon of the Interleukin 22 receptor, alpha 2 gene (IL22RA2) derived from a sequence of retrotransposon of the Mammalian apparent LTR retrotransposons (MaLR) family. Sequencing and analysis of the homologous regions of genomes of several primates indicate that the LTR retrotransposon was inserted into the IL22RA2 gene at least prior to the divergence of Apes and Old World monkeys from a common ancestor (approximately 25 MYA). We hypothesize that the recruitment of the part of LTR as a novel exon in great ape species occurred prior to the divergence of orangutans and humans from a common ancestor (approximately 14 MYA) as a result of a single mutation in the proto-splice site. CONCLUSION: Our analysis of LRTS exonization events has shown that the patterns of LRTS distribution in human exons support the hypothesis that LRTS played a significant role in human gene evolution by providing cis-regulatory sequences; direct incorporation of LTR sequences into protein coding regions was observed less frequently. Combination of computational and experimental approaches used for tracing the history of the LTR exonization process of IL22RA2 gene presents a promising strategy that could facilitate further studies of transposon initiated gene evolution. PMID- 17725823 TI - Regional clinical practice patterns in reproductive endocrinology: a collaborative transnational pilot survey of in vitro fertilization programs in the Middle East. AB - BACKGROUND: This research describes current clinical and demographic features sampled from reproductive endocrinology programs currently offering in vitro fertilization (IVF) in the Middle East. METHODS: Clinic leadership provided data via questionnaire on patient demographics, demand for IVF services, annual cycle volume, indications for IVF, number of embryos transferred, twinning frequency, local regulations governing range of available adjunct therapies, time interval between initial enrollment and beginning IVF as well as information about other aspects of IVF at each center. RESULTS: Data were received from representative IVF clinics (n = 13) in Cyprus, Egypt, Iran, Israel, Jordan, Lebanon, Qatar, Saudi Arabia and Turkey. Mean (+/- SD) age of respondents was 47.8 +/- 8 yrs, with average tenure at their facility of 11.2 +/- 6 yrs. Estimated total number of IVF programs in each nation responding ranged from 1 to 91. All respondents reported individual participation in accredited CME activity within 24 months. 76.9% performed embryo transfers personally; blastocyst transfer was available at 84.6% of centers. PGD was offered at all sites. In this population, male factor infertility accounted for most IVF consultations and the majority (59.1%) of female IVF patients were < 35 yrs of age. Prevalence of smoking among female IVF patients was 7.2%. Average number of embryos transferred was 2.4 (+/- 0.4) for patients at age < 35 yrs, and 2.9 (+/- 0.8) at age > 41 yrs. For these age categories, twinning (any type) was observed in 22.6 (+/- 10.8)% and 13.7 (+/- 10.4)%, respectively. In 2005, the average number of IVF cycles completed at study sites was 1194 (range 363-3500) and 1266 (range 263-4000) in 2006. Frozen embryo transfers accounted for 17.2% of cycles at these centers in 2005. Average interval between initial enrollment and IVF cycle start was 8 weeks (range 0.3 3.5 months). CONCLUSION: This sampling of diverse IVF clinics in the Middle East, believed to be the first of its kind, identified several common factors. Government registry or oversight of clinical IVF practice was limited or nonexistent in most countries, yet number of embryos transferred was nevertheless fairly uniform. Sophisticated reproductive health services in this region are associated with minimal delay (often < 8 weeks) from initial presentation to IVF cycle start. Most Middle East nations do not maintain a comprehensive IVF database, and there is no independent agency to collect transnational data on IVF clinics. Our pilot study demonstrates that IVF programs in the Middle East could contribute voluntarily to collaborative network efforts to share clinical data, improve quality of care, and increase patient access to reproductive services in the region. PMID- 17725824 TI - Mucin-hypersecreting bile duct neoplasm characterized by clinicopathological resemblance to intraductal papillary mucinous neoplasm (IPMN) of the pancreas. AB - BACKGROUND: Although intraductal papillary mucinous neoplasm (IPMN) of the pancreas is acceptable as a distinct disease entity, the concept of mucin secreting biliary tumors has not been fully established. CASE PRESENTATION: We describe herein a case of mucin secreting biliary neoplasm. Imaging revealed a cystic lesion 2 cm in diameter at the left lateral segment of the liver. Duodenal endoscopy revealed mucin secretion through an enlarged papilla of Vater. On the cholangiogram, the cystic lesion communicated with bile duct, and large filling defects caused by mucin were observed in the dilated common bile duct. This lesion was diagnosed as a mucin-secreting bile duct tumor. Left and caudate lobectomy of the liver with extrahepatic bile duct resection and reconstruction was performed according to the possibility of the tumor's malignant behavior. Histological examination of the specimen revealed biliary cystic wall was covered by micropapillary neoplastic epithelium with mucin secretion lacking stromal invasion nor ovarian-like stroma. The patient has remained well with no evidence of recurrence for 38 months since her operation. CONCLUSION: It is only recently that the term "intraductal papillary mucinous neoplasm (IPMN)," which is accepted as a distinct disease entity of the pancreas, has begun to be used for mucin secreting bile duct tumor. This case also seemed to be intraductal papillary neoplasm with prominent cystic dilatation of the bile duct. PMID- 17725825 TI - Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes (ACCEPT-D): design of a randomized study of the efficacy of low-dose aspirin in the prevention of cardiovascular events in subjects with diabetes mellitus treated with statins. AB - BACKGROUND: Despite the high cardiovascular risk, evidence of efficacy of preventive strategies in individuals with diabetes is scant. In particular, recommendations on the use of aspirin in patients with diabetes mostly reflect an extrapolation from data deriving from other high risk populations. Furthermore, the putative additive effects of aspirin and statins in diabetes remain to be investigated. This aspect is of particular interest in the light of the existing debate regarding the need of multiple interventions to reduce total cardiovascular risk, which has also led to the proposal of a polypill. Aim of the study is to evaluate the efficacy of aspirin in the primary prevention of major cardiovascular events in diabetic patients candidate for treatment with statins. These preventive strategies will be evaluated on the top of the other strategies aimed at optimizing the care of diabetic patients in terms of metabolic control and control of the other cardiovascular risk factors. METHODS/DESIGN: The ACCEPT D is an open-label trial assessing whether 100 mg/daily of aspirin prevent cardiovascular events in patients without clinically manifest vascular disease and treated with simvastatin (starting dose 20 mg/die). Eligible patients will be randomly assigned to receive aspirin + simvastatin or simvastatin alone. ELIGIBILITY CRITERIA: male and female individuals aged >=50 years with diagnosis of type 1 or type 2 diabetes, already on treatment with statins or candidate to start the treatment (LDL-cholesterol >=100 mg/dL persisting after 3 months of dietary advise). The primary combined end-point will include cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospital admission for cardiovascular causes (acute coronary syndrome, transient ischemic attack, not planned revascularization procedures, peripheral vascular disease). A total of 515 first events are needed to detect a reduction in the risk of major cardiovascular events of 25% (alpha = 0.05; 1-beta = 0.90). Overall, 5170 patients will be enrolled. The study will be conducted by diabetes specialists and general practitioners. DISCUSSION: The study will provide important information regarding the preventive role of aspirin in diabetes when used on the top of the other strategies aimed to control cardiovascular risk factors. TRIAL REGISTRATION: Current Controlled Trials ISRCTN48110081. PMID- 17725826 TI - Progress towards the child mortality millennium development goal in urban sub Saharan Africa: the dynamics of population growth, immunization, and access to clean water. AB - BACKGROUND: Improvements in child survival have been very poor in sub-Saharan Africa (SSA). Since the 1990 s, declines in child mortality have reversed in many countries in the region, while in others, they have either slowed or stalled, making it improbable that the target of reducing child mortality by two thirds by 2015 will be reached. This paper highlights the implications of urban population growth and access to health and social services on progress in achieving MDG 4. Specifically, it examines trends in childhood mortality in SSA in relation to urban population growth, vaccination coverage and access to safe drinking water. METHODS: Correlation methods are used to analyze national-level data from the Demographic and Health Surveys and from the United Nations. The analysis is complemented by case studies on intra-urban health differences in Kenya and Zambia. RESULTS: Only five of the 22 countries included in the study have recorded declines in urban child mortality that are in line with the MDG target of about 4% per year; five others have recorded an increase; and the 12 remaining countries witnessed only minimal decline. More rapid rate of urban population growth is associated with negative trend in access to safe drinking water and in vaccination coverage, and ultimately to increasing or timid declines in child mortality. There is evidence of intra-urban disparities in child health in some countries like Kenya and Zambia. CONCLUSION: Failing to appropriately target the growing sub-group of the urban poor and improve their living conditions and health status - which is an MDG target itself - may result in lack of improvement on national indicators of health. Sustained expansion of potable water supplies and vaccination coverage among the disadvantaged urban dwellers should be given priority in the efforts to achieve the child mortality MDG in SSA. PMID- 17725827 TI - Functional diversification of the nematode mbd2/3 gene between Pristionchus pacificus and Caenorhabditis elegans. AB - BACKGROUND: Several members of the Methyl-Binding Domain protein family link DNA methylation with chromatin remodeling complexes in vertebrates. Amongst the four classes of MBD proteins, MBD2/3 is the most highly conserved and widespread in metazoans. We have previously reported that an mbd2/3 like gene (mbd-2) is encoded in the genomes of the nematodes Pristionchus pacificus, Caenorhabditis elegans and Caenorhabditis briggsae. RNAi knock-down of mbd-2 in the two Caenorhabditis species results in varying percentages of lethality. RESULTS: Here, we report that a general feature of nematode MBD2/3 proteins seems to be the lack of a bona fide methyl-binding domain. We isolated a null allele of mbd-2 in P. pacificus and show that Ppa-mbd-2 mutants are viable, fertile and display a fully penetrant egg laying defect. This egg laying defect is partially rescued by treatment with acetylcholine or nicotine suggesting a specific function of this protein in vulval neurons. Using Yeast-two-hybrid screens, Ppa-MBD-2 was found to associate with microtubule interacting and vesicle transfer proteins. CONCLUSION: These results imply that MBD2/3 proteins in nematodes are more variable than their relatives in insects and vertebrates both in structure and function. Moreover, nematode MBD2/3 proteins assume functions independent of DNA methylation ranging from the indispensable to the non-essential. PMID- 17725829 TI - Integrated network reconstruction, visualization and analysis using YANAsquare. AB - BACKGROUND: Modeling of metabolic networks includes tasks such as network assembly, network overview, calculation of metabolic fluxes and testing the robustness of the network. RESULTS: YANAsquare provides a software framework for rapid network assembly (flexible pathway browser with local or remote operation mode), network overview (visualization routine and YANAsquare editor) and network performance analysis (calculation of flux modes as well as target and robustness tests). YANAsquare comes as an easy-to-setup program package in Java. It is fully compatible and integrates the programs YANA (translation of gene expression values into flux distributions, metabolite network dissection) and Metatool (elementary mode calculation). As application examples we set-up and model the phospholipid network in the phagosome and genome-scale metabolic maps of S.aureus, S.epidermidis and S.saprophyticus as well as test their robustness against enzyme impairment. CONCLUSION: YANAsquare is an application software for rapid setup, visualization and analysis of small, larger and genome-scale metabolic networks. PMID- 17725828 TI - The epidemiology of low vision and blindness associated with trichiasis in southern Sudan. AB - BACKGROUND: We investigated vision status associated with trachomatous trichiasis (TT) and explored age-sex patterns of low vision and blindness associated with trichiasis in Mankien district of southern Sudan where trachoma prevention and trichiasis surgery were absent. METHODS: A population based survey was undertaken and eligible persons underwent eye examination. Visual acuity (VA) was tested using Snellen E chart and persons with TT identified. Vision status was defined using the WHO categories of visual impairment based on presenting VA: normal vision (VA > or = 6/18 in better eye); low vision (VA < 6/18 but > or = 3/60 in better eye); and blindness (VA < 3/60 in better eye). An ordinal logistic regression model was fitted and age/sex specific distribution of vision status predicted. RESULTS: Overall 341/3,567 persons examined had any TT. Analysis was based on 319 persons, 22 persons were excluded: 20 had both TT and cataract; and 2 had missing VA data. Of the 319 persons: 158(49.5%) had trichiasis-related corneal opacity (CO); bilateral TT and bilateral CO were found in 251(78.7%) and 110 (34.5%), respectively; 146 (45.8%) had low vision or blindness; the ratio of low vision to blindness was 3.2:1; and no sex differences were observed. In our model the predicted distribution of vision status was: normal vision, 53.9% (95% CI 50.9-56.9); low vision, 35.3% (95% CI 33.3-37.2); and blindness, 10.9% (95% CI 9.7-12.0). CONCLUSION: We have reported severe trichiasis and high prevalence of vision loss among persons with trichiasis. Our survey showed that almost 1 in 20 of the entire population suffered low vision or blindness associated with trachoma. The need for trichiasis surgery, trachoma prevention services, and rehabilitation of the blind is acute. PMID- 17725830 TI - Translational machinery of the chaetognath Spadella cephaloptera: a transcriptomic approach to the analysis of cytosolic ribosomal protein genes and their expression. AB - BACKGROUND: Chaetognaths, or arrow worms, are small marine, bilaterally symmetrical metazoans. The objective of this study was to analyse ribosomal protein (RP) coding sequences from a published collection of expressed sequence tags (ESTs) from a chaetognath (Spadella cephaloptera) and to use them in phylogenetic studies. RESULTS: This analysis has allowed us to determine the complete primary structures of 23 out of 32 RPs from the small ribosomal subunit (SSU) and 32 out of 47 RPs from the large ribosomal subunit (LSU). Ten proteins are partially determined and 14 proteins are missing. Phylogenetic analyses of concatenated RPs from six animals (chaetognath, echinoderm, mammalian, insect, mollusc and sponge) and one fungal taxa do not resolve the chaetognath phylogenetic position, although each mega-sequence comprises approximately 5,000 amino acid residues. This is probably due to the extremely biased base composition and to the high evolutionary rates in chaetognaths. However, the analysis of chaetognath RP genes revealed three unique features in the animal Kingdom. First, whereas generally in animals one RP appeared to have a single type of mRNA, two or more genes are generally transcribed for one RP type in chaetognath. Second, cDNAs with complete 5'-ends encoding a given protein sequence can be divided in two sub-groups according to a short region in their 5' ends: two novel and highly conserved elements have been identified (5' TAATTGAGTAGTTT-3' and 5'-TATTAAGTACTAC-3') which could correspond to different transcription factor binding sites on paralog RP genes. And, third, the overall number of deduced paralogous RPs is very high compared to those published for other animals. CONCLUSION: These results suggest that in chaetognaths the deleterious effects of the presence of paralogous RPs, such as apoptosis or cancer are avoided, and also that in each protein family, some of the members could have tissue-specific and extra-ribosomal functions. These results are congruent with the hypotheses of an allopolyploid origin of this phylum and of a ribosome heterogeneity. PMID- 17725832 TI - Exogenous overexpression of nerve growth factor in the urinary bladder produces bladder overactivity and altered micturition circuitry in the lumbosacral spinal cord. AB - BACKGROUND: Exogenous NGF or saline was delivered to the detrusor smooth muscle of female rats for a two-week period using osmotic mini-pumps. We then determined: (1) bladder function using conscious cystometry; (2) organization of micturition reflexes using Fos protein expression in lumbosacral (L5-S1) spinal cord neurons; (3) calcitonin gene-related peptide (CGRP)-immunoreactivity (IR) in lumbosacral spinal cord segments. METHODS: An osmotic pump infused 0.9% NaCl (n = 6) or NGF (n = 6)(2.5 microg/microl solution; 0.5 microl/hr) for two weeks into the bladder wall. NGF bladder content was determined by enzyme-linked immunoassays. Bladder function was assessed with conscious cystometry. Immunohistochemical and imaging techniques were used to determine the distribution of Fos-IR cells and CGRP expression in the L5-S1 spinal cord in saline and NGF-treated rats two hours after intravesical saline distention. Fos expression and CGRP-IR in NGF-treated rats with bladder distention was compared to that observed in cyclophosphamide (CYP; 75 mg/kg; i.p.) treated rats with bladder distention. RESULTS: Two-week infusion of NGF into the bladder wall increased bladder weight, reduced bladder capacity (60%), reduced the intercontraction interval (60%) and increased the amplitude of non-voiding contractions. NGF treatment and intravesical saline distention (2 hr) increased expression of Fos protein in L6-S1 spinal cord and altered the distribution pattern of Fos-IR cells. CGRP-IR in the lumbosacral spinal cord was also increased after NGF treatment. CONCLUSION: These data suggest that NGF infusion into the bladder wall induces bladder overactivity, can reveal a "nociceptive" Fos expression pattern in the spinal cord in response to a non-noxious bladder stimulus and increases CGRP-IR in the lumbosacral spinal cord. PMID- 17725831 TI - Short-term oleoyl-estrone treatment affects capacity to manage lipids in rat adipose tissue. AB - BACKGROUND: Short-term OE (oleoyl-estrone) treatment causes significant decreases in rat weight mainly due to adipose tissue loss. The aim of this work was to determine if OE treatment affects the expression of genes that regulate lipid metabolism in white adipose tissue. RESULTS: Gene expression in adipose tissue from female treated rats (48 hours) was analysed by hybridization to cDNA arrays and levels of specific mRNAs were determined by real-time PCR. Treatment with OE decreased the expression of 232 genes and up-regulated 75 other genes in mesenteric white adipose tissue. The use of real-time PCR validate that, in mesenteric white adipose tissue, mRNA levels for Lipoprotein Lipase (LPL) were decreased by 52%, those of Fatty Acid Synthase (FAS) by 95%, those of Hormone Sensible Lipase (HSL) by 32%, those of Acetyl CoA Carboxylase (ACC) by 92%, those of Carnitine Palmitoyltransferase 1b (CPT1b) by 45%, and those of Fatty Acid Transport Protein 1 (FATP1) and Adipocyte Fatty Acid Binding Protein (FABP4) by 52% and 49%, respectively. Conversely, Tumour Necrosis Factor (TNFalpha) values showed overexpression (198%). CONCLUSION: Short-term treatment with OE affects adipose tissue capacity to extract fatty acids from lipoproteins and to deal with fatty acid transport and metabolism. PMID- 17725834 TI - Organizational interventions employing principles of complexity science have improved outcomes for patients with Type II diabetes. AB - BACKGROUND: Despite the development of several models of care delivery for patients with chronic illness, consistent improvements in outcomes have not been achieved. These inconsistent results may be less related to the content of the models themselves, but to their underlying conceptualization of clinical settings as linear, predictable systems. The science of complex adaptive systems (CAS), suggests that clinical settings are non-linear, and increasingly has been used as a framework for describing and understanding clinical systems. The purpose of this study is to broaden the conceptualization by examining the relationship between interventions that leverage CAS characteristics in intervention design and implementation, and effectiveness of reported outcomes for patients with Type II diabetes. METHODS: We conducted a systematic review of the literature on organizational interventions to improve care of Type II diabetes. For each study we recorded measured process and clinical outcomes of diabetic patients. Two independent reviewers gave each study a score that reflected whether organizational interventions reflected one or more characteristics of a complex adaptive system. The effectiveness of the intervention was assessed by standardizing the scoring of the results of each study as 0 (no effect), 0.5 (mixed effect), or 1.0 (effective). RESULTS: Out of 157 potentially eligible studies, 32 met our eligibility criteria. Most studies were felt to utilize at least one CAS characteristic in their intervention designs, and ninety-one percent were scored as either "mixed effect" or "effective." The number of CAS characteristics present in each intervention was associated with effectiveness (p = 0.002). Two individual CAS characteristics were associated with effectiveness: interconnections between participants and co-evolution. CONCLUSION: The significant association between CAS characteristics and effectiveness of reported outcomes for patients with Type II diabetes suggests that complexity science may provide an effective framework for designing and implementing interventions that lead to improved patient outcomes. PMID- 17725833 TI - Visualizing differences in phylogenetic information content of alignments and distinction of three classes of long-branch effects. AB - BACKGROUND: Published molecular phylogenies are usually based on data whose quality has not been explored prior to tree inference. This leads to errors because trees obtained with conventional methods suppress conflicting evidence, and because support values may be high even if there is no distinct phylogenetic signal. Tools that allow an a priori examination of data quality are rarely applied. RESULTS: Using data from published molecular analyses on the phylogeny of crustaceans it is shown that tree topologies and popular support values do not show existing differences in data quality. To visualize variations in signal distinctness, we use network analyses based on split decomposition and split support spectra. Both methods show the same differences in data quality and the same clade-supporting patterns. Both methods are useful to discover long-branch effects. We discern three classes of long branch effects. Class I effects consist of attraction of terminal taxa caused by symplesiomorphies, which results in a false monophyly of paraphyletic groups. Addition of carefully selected taxa can fix this effect. Class II effects are caused by drastic signal erosion. Long branches affected by this phenomenon usually slip down the tree to form false clades that in reality are polyphyletic. To recover the correct phylogeny, more conservative genes must be used. Class III effects consist of attraction due to accumulated chance similarities or convergent character states. This sort of noise can be reduced by selecting less variable portions of the data set, avoiding biases, and adding slower genes. CONCLUSION: To increase confidence in molecular phylogenies an exploratory analysis of the signal to noise ratio can be conducted with split decomposition methods. If long-branch effects are detected, it is necessary to discern between three classes of effects to find the best approach for an improvement of the raw data. PMID- 17725835 TI - Which doctors and with what problems contact a specialist service for doctors? A cross sectional investigation. AB - BACKGROUND: In the United Kingdom, specialist treatment and intervention services for doctors are underdeveloped. The MedNet programme, created in 1997 and funded by the London Deanery, aims to fill this gap by providing a self-referral, face to-face, psychotherapeutic assessment service for doctors in London and South East England. MedNet was designed to be a low-threshold service, targeting doctors without formal psychiatric problems. The aim of this study was to delineate the characteristics of doctors utilising the service, to describe their psychological morbidity, and to determine if early intervention is achieved. METHODS: A cross-sectional study including all consecutive self-referred doctors (n = 121, 50% male) presenting in 2002-2004 was conducted. Measures included standardised and bespoke questionnaires both self-report and clinician completed. The multi-dimensional evaluation included: demographics, CORE (CORE-OM, CORE Workplace and CORE-A) an instrument designed to evaluate the psychological difficulties of patients referred to outpatient services, Brief Symptom Inventory to quantify caseness and formal psychiatric illness, and Maslach Burnout Inventory. RESULTS: The most prevalent presenting problems included depression, anxiety, interpersonal, self-esteem and work-related issues. However, only 9% of the cohort were identified as severely distressed psychiatrically using this measure. In approximately 50% of the sample, problems first presented in the preceding year. About 25% were on sick leave at the time of consultation, while 50% took little or no leave in the prior 12 months. A total of 42% were considered to be at some risk of suicide, with more than 25% considered to have a moderate to severe risk. There were no significant gender differences in type of morbidity, severity or days off sick. CONCLUSION: Doctors displayed high levels of distress as reflected in the significant proportion of those who were at some risk of suicide; however, low rates of severe psychiatric illness were detected. These findings suggest that MedNet clients represent both ends of the spectrum of severity, enabling early clinical engagement for a significant proportion of cases that is of importance both in terms of personal health and protecting patient care, and providing a timely intervention for those who are at risk, a group for whom rapid intervention services are in need and an area that requires further investigation in the UK. PMID- 17725836 TI - Chagas disease: an impediment in achieving the Millennium Development Goals in Latin America. AB - BACKGROUND: Achieving sustainable economic and social growth through advances in health is crucial in Latin America within the framework of the United Nations Millennium Development Goals. DISCUSSION: Health-related Millennium Development Goals need to incorporate a multidimensional approach addressing the specific epidemiologic profile for each region of the globe. In this regard, addressing the cycle of destitution and suffering associated with infection with Trypanosoma cruzi, the causal agent of Chagas disease of American trypanosomiasis, will play a key role to enable the most impoverished populations in Latin America the opportunity to achieve their full potential. Most cases of Chagas disease occur among forgotten populations because these diseases persist exclusively in the poorest and the most marginalized communities in Latin America. SUMMARY: Addressing the cycle of destitution and suffering associated with T. cruzi infection will contribute to improve the health of the most impoverished populations in Latin America and will ultimately grant them with the opportunity to achieve their full economic potential. PMID- 17725837 TI - Doppler ultrasound scoring to predict chemotherapeutic response in advanced breast cancer. AB - BACKGROUND: Doppler ultrasonography (US) is increasingly being utilized as an imaging modality in breast cancer. It is used to study the vascular characteristics of the tumor. Neoadjuvant chemotherapy is the standard modality of treatment in locally advanced breast cancer. Histological examination remains the gold standard to assess the chemotherapy response. However, based on the color Doppler findings, a new scoring system that could predict histological response following chemotherapy is proposed. METHODS: Fifty cases of locally advanced infiltrating duct carcinoma of the breast were studied. The mean age of the patients was 44.5 years. All patients underwent clinical, Doppler and histopathological assessment followed by three cycles of CAF (Cyclophosphamide, Adriamycin and 5-Fluorouracil) chemotherapy, repeat clinical and Doppler examination and surgery. The resected specimens were examined histopathologically and histological response was correlated with Doppler findings. The Doppler characteristics of the tumor were graded as 1-4 for <25%, 25-50%, >50% and complete disappearance of flow signals respectively. A cumulative score was calculated and compared with histopathological response. Results were analyzed using Chi square test, sensitivity, specificity, positive and negative predictive values. RESULTS: The maximum Doppler score according to the proposed scoring system was twelve and minimum three. Higher scores corresponded with a more favorable histopathological response. Twenty four patients had complete response to chemotherapy. Sixteen of these 24 patients (66.7%) had a cumulative Doppler score more than nine. The sensitivity of cumulative score >5 was 91.7% and specificity was 38.5%. The area under the ROC curve of the cumulative score >9 was 0.72. CONCLUSION: Doppler scoring can be accurately used to objectively predict the response to chemotherapy in patients with locally advanced breast cancer and it correlates well with histopathological response. PMID- 17725838 TI - Expedient syntheses of the N-heterocyclic carbene precursor imidazolium salts IPr.HCl, IMes.HCl and IXy.HCl. AB - The 1,3-diaryl-imidazolium chlorides IPr.HCl (aryl = 2,6-diisopropylphenyl), IMes.HCl (aryl = 2,4,6-trimethylphenyl) and IXy.HCl (aryl = 2,6-dimethylphenyl), precursors to widely used N-heterocyclic carbene (NHC) ligands and catalysts, were prepared in high yields (81%, 69% and 89%, respectively) by the reaction of 1,4-diaryl-1, 4-diazabutadienes, paraformaldehyde and chlorotrimethylsilane in dilute ethyl acetate solution. A reaction mechanism involving a 1,5-dipolar electrocyclization is proposed. PMID- 17725839 TI - Utility of interferon-gamma ELISPOT assay responses in highly tuberculosis exposed patients with advanced HIV infection in South Africa. AB - BACKGROUND: Interferon-gamma (IFN-gamma) ELISPOT assays incorporating Mycobacterium tuberculosis-specific antigens are useful in the diagnosis of tuberculosis (TB) or latent infection. However, their utility in patients with advanced HIV is unknown. We studied determinants of ELISPOT responses among patients with advanced HIV infection (but without active TB) living in a South African community with very high TB notification rates. METHODS: IFN-gamma responses to ESAT-6 and CFP-10 in overnight ELISPOT assays and in 7-day whole blood assays (WBA) were compared in HIV-infected patients (HIV+, n = 40) and healthy HIV-negative controls (HIV-, n = 30) without active TB. Tuberculin skin tests (TSTs) were also done. RESULTS: ELISPOTs, WBAs and TSTs were each positive in >70% of HIV- controls, reflecting very high community exposure to M. tuberculosis. Among HIV+ patients, quantitative WBA responses and TSTs (but not the proportion of positive ELISPOT responses) were significantly impaired in those with CD4 cell counts <100 cells/mul compared to those with higher counts. In contrast, ELISPOT responses (but not WBA or TST) were strongly related to history of TB treatment; a much lower proportion of HIV+ patients who had recently completed treatment for TB (n = 19) had positive responses compared to those who had not been treated (11% versus 62%, respectively; P < 0.001). Multivariate analysis confirmed that ELISPOT responses had a strong inverse association with a history of recent TB treatment (adjusted OR = 0.06, 95%CI = 0.10-0.40, P < 0.01) and that they were independent of CD4 cell count and viral load. Among HIV+ individuals who had not received TB treatment both the magnitude and proportion of positive ELISPOT responses (but not TST or WBA) were similar to those of HIV-negative controls. CONCLUSION: The proportion of positive ELISPOT responses in patients with advanced HIV infection was independent of CD4 cell count but had a strong inverse association with history of TB treatment. This concurs with the previously documented low TB risk among patients in this cohort with a history of recent treatment for TB. These data suggest ELISPOT assays may be useful for patient assessment and as an immuno-epidemiological research tool among patients with advanced HIV and warrant larger scale prospective evaluation. PMID- 17725840 TI - Identifying genes preferentially expressed in undifferentiated embryonic stem cells. AB - BACKGROUND: The mechanism involved in the maintenance and differentiation of embryonic stem (ES) cells is incompletely understood. RESULTS: To address this issue, we have developed a retroviral gene trap vector that can target genes expressed in undifferentiated ES cells. This gene trap vector harbors both GFP and Neo reporter genes. G-418 drug resistance was used to select ES clones in which the vector was integrated into transcriptionally active loci. This was then followed by GFP FACS profiling to identify ES clones with reduced GFP fluorescence and, hence, reduced transcriptional activity when ES cells differentiate. Reduced expression of the GFP reporter in six of three hundred ES clones in our pilot screening was confirmed to be down-regulated by Northern blot analysis during ES cell differentiation. These six ES clones represent four different genes. Among the six integration sites, one was at Zfp-57 whose gene product is known to be enriched in undifferentiated ES cells. Three were located in an intron of a novel isoform of CSL/RBP-J kappa which encodes the key transcription factor of the LIN-12/Notch pathway. Another was inside a gene that may encode noncoding RNA transcripts. The last integration event occurred at a locus that may harbor a novel gene. CONCLUSION: Taken together, we demonstrate the use of a novel retroviral gene trap vector in identifying genes preferentially expressed in undifferentiated ES cells. PMID- 17725841 TI - A comprehensive system for evaluation of remote sequence similarity detection. AB - BACKGROUND: Accurate and sensitive performance evaluation is crucial for both effective development of better structure prediction methods based on sequence similarity, and for the comparative analysis of existing methods. Up to date, there has been no satisfactory comprehensive evaluation method that (i) is based on a large and statistically unbiased set of proteins with clearly defined relationships; and (ii) covers all performance aspects of sequence-based structure predictors, such as sensitivity and specificity, alignment accuracy and coverage, and structure template quality. RESULTS: With the aim of designing such a method, we (i) select a statistically balanced set of divergent protein domains from SCOP, and define similarity relationships for the majority of these domains by complementing the best of information available in SCOP with a rigorous SVM based algorithm; and (ii) develop protocols for the assessment of similarity detection and alignment quality from several complementary perspectives. The evaluation of similarity detection is based on ROC-like curves and includes several complementary approaches to the definition of true/false positives. Reference-dependent approaches use the 'gold standard' of pre-defined domain relationships and structure-based alignments. Reference-independent approaches assess the quality of structural match predicted by the sequence alignment, with respect to the whole domain length (global mode) or to the aligned region only (local mode). Similarly, the evaluation of alignment quality includes several reference-dependent and -independent measures, in global and local modes. As an illustration, we use our benchmark to compare the performance of several methods for the detection of remote sequence similarities, and show that different aspects of evaluation reveal different properties of the evaluated methods, highlighting their advantages, weaknesses, and potential for further development. CONCLUSION: The presented benchmark provides a new tool for a statistically unbiased assessment of methods for remote sequence similarity detection, from various complementary perspectives. This tool should be useful both for users choosing the best method for a given purpose, and for developers designing new, more powerful methods. The benchmark set, reference alignments, and evaluation codes can be downloaded from ftp://iole.swmed.edu/pub/evaluation/. PMID- 17725842 TI - A survey of health professions students for knowledge, attitudes, and confidence about tuberculosis, 2005. AB - BACKGROUND: In 2003 the NIH perceived a need to strengthen teaching about tuberculosis (TB) to health professions students. The National Tuberculosis Curriculum Consortium (NTCC) was funded to meet this need. The purpose of this study was to survey students enrolled in NTCC schools prior to NTCC-developed educational materials being made available to faculty. METHODS: A self administered survey for students in NTCC schools to establish a baseline level of knowledge, attitudes, and confidence about tuberculosis. RESULTS: 1480/2965 (50%) students in 28 programs in 20 NTCC schools completed the survey. If public health students are eliminated from totals (only 61 respondents of 765 public health students), the overall response proportion for the seven clinically-related disciplines was 64.5%. The majority (74%) were in schools of medicine (MD/DO), undergraduate nursing (BSN), and pharmacy (PharmD); others were in programs for physician assistants (PA), advanced practice nursing (NP/APN), respiratory therapy (RT), clinical laboratory sciences (MT/CLS), and public health (MPH). Almost 90% had attended at least one lecture about TB. Although 91.4% knew TB was transmitted via aerosols, about one-third did not know the method for administering tuberculin, or that Bacillus Calmette-Guerin (BCG) vaccine was not a contraindication to TB skin testing. Fewer than two-thirds knew that about 10% of people in the U.S.A. who have latent tuberculosis infection (LTBI) and a normal immune system will develop TB disease, or that BCG is not part of the routine vaccination program in the U.S.A. because it complicates surveillance for new TB infection. CONCLUSION: There is room for improvement in knowledge, attitudes, and confidence about TB by health professions students surveyed. The NTCC-developed educational products may be used by faculty to improve student performance to be assessed with future surveys. PMID- 17725844 TI - Power analysis for genome-wide association studies. AB - BACKGROUND: Genome-wide association studies are a promising new tool for deciphering the genetics of complex diseases. To choose the proper sample size and genotyping platform for such studies, power calculations that take into account genetic model, tag SNP selection, and the population of interest are required. RESULTS: The power of genome-wide association studies can be computed using a set of tag SNPs and a large number of genotyped SNPs in a representative population, such as available through the HapMap project. As expected, power increases with increasing sample size and effect size. Power also depends on the tag SNPs selected. In some cases, more power is obtained by genotyping more individuals at fewer SNPs than fewer individuals at more SNPs. CONCLUSION: Genome wide association studies should be designed thoughtfully, with the choice of genotyping platform and sample size being determined from careful power calculations. PMID- 17725843 TI - Duloxetine in the treatment of major depressive disorder: an open-label study. AB - BACKGROUND: Major depressive disorder (MDD) is a chronic and highly disabling condition. Existing pharmacotherapies produce full remission in only 30% to 40% of treated patients. Antidepressants exhibiting dual reuptake inhibition of both serotonin (5-HT) and norepinephrine (NE) may achieve higher rates of remission compared with those acting upon a single neurotransmitter. In this study, the safety and efficacy of duloxetine, a potent dual reuptake inhibitor of 5-HT and NE, were examined. METHODS: Patients (N = 533) meeting DSM-IV criteria for MDD received open-label duloxetine (60 mg once a day [QD]) for 12 weeks during the initial phase of a relapse prevention trial. Patients were required to have a 17 item Hamilton Rating Scale for Depression (HAMD17) total score >or=18 and a Clinical Global Impression of Severity (CGI-S) score >or=4 at baseline. Efficacy measures included the HAMD17 total score, HAMD17 subscales, the CGI-S, the Patient Global Impression of Improvement (PGI-I) scale, Visual Analog Scales (VAS) for pain, and the Symptom Questionnaire, Somatic Subscale (SQ-SS). Quality of life was assessed using the Sheehan Disability Scale (SDS) and the Quality of Life in Depression Scale (QLDS). Safety was evaluated by recording spontaneously reported treatment-emergent adverse events, changes in vital signs and laboratory analytes, and the Patient Global Impression of Sexual Function (PGI-SF) scale. RESULTS: The rate of discontinuation due to adverse events was 11.3%. Treatment emergent adverse events reported by >or=10% duloxetine-treated patients were nausea, headache, dry mouth, somnolence, insomnia, and dizziness. Following 12 weeks of open-label duloxetine therapy, significant improvements were observed in all assessed efficacy and quality of life measures. In assessments of depression severity (HAMD17, CGI-S) the magnitude of symptom improvement continued to increase at each study visit, while for painful physical symptoms the onset of improvement was rapid and reached a maximum after 2 to 3 weeks of treatment. CONCLUSION: In this open-label phase of a relapse prevention study, duloxetine (60 mg QD) was shown to be safe and effective in the treatment of MDD. PMID- 17725846 TI - Developing paediatric medicines: identifying the needs and recognizing the challenges. AB - There is a significant need for research and development into paediatric medicines. Only a small fraction of the drugs marketed and utilized as therapeutic agents in children have been clinically evaluated. The majority of marketed drugs are either not labelled, or inadequately labelled, for use in paediatric patients. The absence of suitable medicines or critical safety and efficacy information poses significant risks to a particularly vulnerable patient population. However, there are many challenges associated with developing medicines for the paediatric population and this review paper is intended to highlight these. The paediatric population is made up of a wide range of individuals of substantially varied physical size, weight and stage of physiological development. Experimentation on children is considered by many to be unethical, resulting in difficulties in obtaining critical safety data. Clinical trials are subject to detailed scrutiny by the various regulatory bodies who have recently recognized the need for pharmaceutical companies to invest in paediatric medicines. The costs associated with paediatric product development could result in poor or negative return on investment and so incentives have been proposed by the EU and US regulatory bodies. Additionally, some commonly used excipients may be unsuitable for use in children; and some dosage forms may be undesirable to the paediatric population. PMID- 17725845 TI - Glutamatergic alterations in the cortex of genetic absence epilepsy rats. AB - BACKGROUND: In absence epilepsy, the neuronal hyper-excitation and hyper synchronization, which induce spike and wave discharges in a cortico-thalamic loop are suspected to be due to an imbalance between GABA and glutamate (GLU) neurotransmission. In order to elucidate the role played by GLU in disease outcome, we measured cortical and thalamic extracellular levels of GLU and GABA. We used an in vivo quantitative microdialysis approach (no-net-flux method) in an animal model of absence epilepsy (GAERS). In addition, by infusing labelled glutamate through the microdialysis probe, we studied in vivo glutamate uptake in the cortex and thalamus in GAERS and non-epileptic control (NEC) rats. Expression of the vesicular glutamate transporters VGLUT1 and VGLUT2 and a synaptic component, synaptophysin, was also measured. RESULTS: Although extracellular concentrations of GABA and GLU in the cortex and thalamus were not significantly different between GAERS and NEC rats, cortical GLU uptake was significantly decreased in unrestrained awake GAERS. Expression of VGLUT2 and synaptophysin was increased in the cortex of GAERS compared to NEC rats, but no changes were observed in the thalamus. CONCLUSION: The specific decrease in GLU uptake in the cortex of GAERS linked to synaptic changes suggests impairment of the glutamatergic terminal network. These data support the idea that a change in glutamatergic neurotransmission in the cortex could contribute to hyperexcitability in absence epilepsy. PMID- 17725847 TI - Solid lipid nanoparticles (SLN) as carriers for the topical delivery of econazole nitrate: in-vitro characterization, ex-vivo and in-vivo studies. AB - Solid lipid nanoparticles (SLN) designed for topical administration of econazole nitrate (ECN), were prepared by o/w high-shear homogenization method using different ratios of lipid and drug (5:1 and 10:1). SLN were characterized in terms of particle size, morphology, encapsulation efficiency and crystalline structure. After incorporation of SLN into hydrogels, rheological measurements were performed, and ex-vivo drug permeation tests were carried out using porcine stratum corneum (SC). In-vivo study of percutaneous absorption of ECN as a function of application time and composition of gels was carried out by tape stripping technique. Penetration tests of the drug from a conventional gel were performed as comparison. High-shear homogenization method resulted in a good technique for preparation of ECN-loaded SLN. Particles had a mean diameter of about 150 nm and a regular shape and smooth surface. The encapsulation efficiency values were about 100%. Ex-vivo tests showed that SLN were able to control the drug release through the SC; the release rate depended upon the lipid content on the nanoparticles. In-vivo studies demonstrated that SLN promoted a rapid penetration of ECN through the SC after 1 h and improved the diffusion of the drug in the deeper skin layers after 3 h of application compared with the reference gel. PMID- 17725848 TI - Novel, cell-penetrating molecular transporters with flexible backbones and permanently charged side-chains. AB - Various cell-penetrating peptides have been discovered recently that can translocate across plasma membranes and can even carry large cargo molecules into the cells. Because under physiological conditions most of these peptides carry considerable positive charges due to the presence of basic amino acids such as arginine, we decided to investigate whether molecular transporters composed of permanently charged side-chains also possess such cell penetrating ability. Arginine-rich oligomers that have a backbone with increased flexibility due to incorporation of non-alpha-amino acids (epsilon-aminocaproic acid) have been found to be effective molecular transporters. Here, we report the preparation of analogue structures by replacing the arginine residues with the quaternary form of a novel redox amino acid (Nys(+)) that contain a trigonelline moiety; it has already been shown possible to replace the original basic amino acid side-chain of neuropeptides without significant activity-loss due to the sufficiently close steric and electronic analogy between the new Nys(+) and the original side-chains (in their protonated form, e.g., Arg(+), Lys(+)). A nonamer analogue showed transporter activity resulting in increased cellular uptake in human carcinoma (HeLa) cells. PMID- 17725849 TI - Central nervous system distribution kinetics of indinavir in rats. AB - The central nervous system (CNS) distribution kinetics of indinavir were extensively evaluated using a combinational in-vivo model comprising the integration plot method (a single-passage approach) and neuropharmacokinetic method (a multiple-passage approach). A 5 mg kg(-1) dose of indinavir was administered intravenously to rats. Blood and cerebrospinal fluid (CSF) samples and whole brain were collected from the animals at specified time points and the drug concentration in each sample was determined using a high-performance liquid chromatography method. For the neuropharmacokinetic study, the simultaneous plasma, CSF and brain concentrations were fitted to an integrated model, which resulted in the estimation of the influx (K(in)) and efflux (K(out)) rate constants of the drug to/from CSF and brain parenchyma. The integration plot method involved plotting the brain-plasma or CSF-plasma concentration ratios (K(p, app)) against AUC(0-->t)/C(p(t)), and estimating the uptake clearance of the drug by brain/CSF from the slope of the initial linear portion of the plot. The K(in) and K(out) values of the drug to/from CSF were estimated to be 2.42 x 10(-2) and 13.26 x 10(-2)min(-1), respectively, and the corresponding values for brain parenchyma were 1.02 x 10(-2) and 1.32 x 10(-2) min(-1), respectively. The uptake clearances of indinavir by CSF and brain parenchyma were 8.89 and 8.38microL min(-1)g(-1), respectively. The permeability surface area products of the drug for the blood-brain barrier and blood-CSF barrier were estimated as 1.05 x 10(-2) and 2.45 x 10(-2) mLmin(-1)g(-1), respectively. The estimated kinetic parameters indicated limited CNS entry of the drug because of the limited blood brain barrier permeability and the efficient drug efflux from CNS, particularly from CSF. PMID- 17725850 TI - A novel synthetic oleanolic acid derivative with amino acid conjugate suppresses tumour growth by inducing cell cycle arrest. AB - Oleanolic acid (3beta-hydroxy-olean-12-en-28-oic acid; OA) has a wide variety of bioactivities and is used for medicinal purposes in many Asian countries. Various derivatives of OA have been synthesized in attempts to improve the potency. Here we describe the anti-tumour activity of a novel OA derivative, N-[(3beta)-3 (acetyloxy)-28-oxoolean-12-en-28-yl]-glycine methyl ester (AOA-GMe). AOAGMe was a more potent inhibitor of the growth of B16 melanoma cells than its parent compound OA, both in-vitro and in-vivo. AOA-GMe also exhibited dose-dependent inhibition of human K562 leukaemia cells, but had almost no toxicity in normal human peripheral blood mononuclear cells. AOA-GMe induced cell cycle arrest in G0/G1 and blocked G1-S transition, which correlated well with marked decreases in levels of cyclin D, cyclin-dependent kinase CDK4 and phosphorylated retinoblastoma protein, and increases in the cyclin-dependent kinase inhibitor p15. OA did not show such activities. These results suggest that AOA-GMe may induce growth arrest in tumour cells through regulation of proteins involved in the cell cycle. PMID- 17725851 TI - Effects of low oxygen levels on the expression and function of transporter OCTN2 in BeWo cells. AB - Although hypoxia is normal in early pregnancy, low placental oxygen concentrations later in pregnancy are often linked to complications such as pre eclampsia and intrauterine growth restriction. The effects of low oxygen levels on drug and nutrient uptake via the organic cation transporter OCTN2 has been studied in BeWo cells, an in-vitro model of human trophoblast. BeWo cells were cultured under 20% (control) or 2% O(2) (hypoxia) for 48 h before each experiment. In-vitro hypoxia was also simulated by the addition of CoCl(2) to the cell culture medium. RT-PCR indicated increased transcription of OCTN2 in BeWo cells cultured under hypoxia, but Western blots did not show a corresponding increase in the amount of OCTN2 protein in the hypoxic cells compared with control. Hypoxia resulted in significant reductions in OCTN2-mediated carnitine uptake. Decreased placental transport of carnitine may lead to symptoms of carnitine deficiency in infants from hypoxic pregnancies, whether caused by high altitude, pre-eclampsia or other factors. The OCTN1 substrate ergothioneine reversed the effects of hypoxia on carnitine transport, but identical concentrations of N-acetylcysteine, another water-soluble intracellular antioxidant, did not have the same effect. PMID- 17725852 TI - Protective effect of (+)-catechin against gastric mucosal injury induced by ischaemia-reperfusion in rats. AB - Ischaemia and reperfusion are known to induce gastric lesions, predominantly due to excessive formation of reactive oxygen metabolites, adhesion of neutrophils to endothelial cells, microvascular dysfunction, gastric acid secretion, endogenous histamine and gastrin release. We have studied the effect of (+)-catechin on a gastric ulcer model involving damage to gastric injury by ischaemia- reperfusion (I/R) in rats. (+)-Catechin 50 mg kg(-1)administered orally, once daily for three days after the initiation of I/R injury showed a significant (P<0.001) anti-ulcer activity against mucosal dam- age. However, (+)-catechin significantly decreased the lipid peroxidation and increased the level of catalase in the I/R condition. Elevated levels of alkaline phosphatase in the I/R group was significantly lowered (P<0.01) by (+)-catechin. The amount of H(+)K(+)ATPase was significantly decreased (P<0.001) in (+)-catechin-treated as compared with I/R rats. (+) Catechin significantly decreased elevated plasma histamine (P<0.05) and corticosterone (P<0.05). The results suggested that (+)-catechin protected gastric mucosa against ischaemia-reperfusion-induced gastric ulcers by its antioxidant activity and mucus protection. PMID- 17725853 TI - Involvement of kappa opioid receptors in formalin-induced inhibition of analgesic tolerance to morphine in mice. AB - This study examined the role of kappa opioid receptors (KOR) in the mechanism underlying tolerance to the analgesic effects of morphine induced by chronic pain. The analgesic effect of morphine (10 mg kg(-1)), estimated by the tail flick test in mice, gradually decreased during repeated daily morphine treatment. A significant decrease in the analgesic effect of morphine was seen on the fifth day of repeated morphine treatment compared with the first day. Chronic pain was induced by subcutaneous administration of 2% formalin into the dorsal part of the left hind paw, which significantly inhibited development of tolerance to morphine analgesia. The effect of formalin-induced pain on inhibition of morphine tolerance was reversed by the KOR antagonist nor-binaltorphimine. Furthermore, an antisense oligodeoxynucleotide, but not a missense oligodeoxynucleotide, against KOR completely suppressed the inhibitory effect of formalin-induced pain on morphine tolerance. Naltrindole, an antagonist of delta opioid receptor, did not affect chronic-pain-induced tolerance to morphine. Our findings show that the inhibitory effect of chronic pain on analgesic tolerance to morphine is mediated by KOR rather than delta opioid receptors. PMID- 17725854 TI - The influence of improved glycaemic control with chlorpropamide on microvascular reactivity and nitric oxide synthase activity in diabetic rats. AB - Hyperglycaemia is a primary cause of vascular complications in diabetes. A hallmark of these vascular complications is endothelial cell dysfunction, which is partly due to reduced production of nitric oxide. The aim of this study was to verify the influence of improved glycaemic control with chlorpropamide on microvascular reactivity, endothelial nitric oxide synthase (e-NOS) expression, and NOS activity in neonatal streptozotocin-induced diabetic rats (n-STZ). Diabetes was induced by STZ injection into neonates Wistar rats. n-STZ diabetic rats were treated with chlorpropamide (200 mg kg(-1), 15 days, by gavage). The changes in mesenteric arteriolar and venular diameters were determined in anaesthetized control and n-STZ diabetic rats, before and after topical application of acetylcholine, bradykinin and sodium nitroprusside (SNP). We also assessed e-NOS expression (using polymerase chain reaction after reverse transcription of mRNAs into cDNAs) and NOS activity (conversion of L-arginine to citrulline) in the mesenteric vascular bed of chlorpropamide-treated n-STZ, vehicle-treated n-STZ, and control rats. In n-STZ, chlorpropamide treatment reduced high glycaemic levels, improved glucose tolerance and homoeostatic model assessment (HOMA-beta), and restored NOS activity. Impaired vasodilator responses of arterioles and venules to acetylcholine, bradykinin and SNP were partially corrected by chlorpropamide treatment in n-STZ. We concluded that improved metabolic control and restored NOS activity might be collaborating with improved microvascular reactivity found in chlorpropamide-treated n-STZ. PMID- 17725856 TI - Theogallin and L-theanine as active ingredients in decaffeinated green tea extract: I. electrophysiological characterization in the rat hippocampus in vitro. AB - The in-vitro hippocampus slice preparation was used to mimic a physiological situation where nervous tissue is exposed directly to the water soluble extract of green tea and some of its constituents. This investigation provides evidence that L-theanine- and theogallin-enriched decaffeinated green tea extract is able to change the physiological pattern of electrical hippocampus activity in a concentration dependent manner (EC50 3 mg L(-1)). Of the seven fractions or single components tested (fraction containing all amino acids without L-theanine, fractions containing all amino acids plus L-theanine, glutamic acid, theogallin, its metabolites quinic acid and gallic acid, and L-theanine alone), glutamic acid produced the strongest changes in terms of increased population spike amplitude after single stimuli and increased long-term potentiation, commonly taken as representative for enhancement of spatial and time dependent memory. The presence of theogallin alone shifted the activity in the same direction. Similar results as with theogallin were obtained in the presence of quinic acid. No effect was seen with gallic acid. Opposite changes (decrease of population spike amplitude and attenuated long-term potentiation) were observed in the presence of L theanine alone. No effects were detected during the addition of the amino acid mixture unless L-theanine was added, leading to a decrease of the responses as observed for the action of L-theanine alone. The results provide evidence for the involvement of several active principles in the action of enriched green tea extract on electrical brain activity. The overall enhancement of hippocampal pyramidal cell responses as observed for the crude extract seems to be due to the combined action of glutamic acid and theogallin (or its presumable metabolite quinic acid), whereas L-theanine seems to have an opposite effect. However, this action was not strong enough to antagonize the effects of glutamic acid and theogallin. The results are in line with the observation that the tested green tea extract improves cognition at concomitant mental relaxation in man. PMID- 17725855 TI - Scavenging properties of metronidazole on free oxygen radicals in a skin lipid model system. AB - Reactive oxygen species (ROS) play a vital role in the pathophysiology of the skin disease rosacea, a chronic, genetically-determined and UV-triggered disease, leading to facial redness and blemishes and exhibiting a deep impact on a patient's self-esteem and quality of life. ROS can cause oxidative damage to nucleic acids, sugars, proteins and lipids, thereby contributing to adverse effects on the skin. Metronidazole has been the first-line topical agent therapy for many years; nevertheless the mechanism of action is still not well understood. The therapeutic efficacy of metronidazole has been attributed to its antioxidant effects, which can involve two pathways: decreased generation of ROS within tissues or scavenging and inactivation of existing ROS. Previous investigations have shown that metronidazole reduces ROS by decreasing ROS production in cellular in-vitro systems. The aim of the following study was to demonstrate that metronidazole additionally exhibits antioxidative properties in a cell-free system, by acting as an antioxidant scavenger. A simple skin lipid model (oxidative) system and a complex skin adapted lipid system in conjunction with thiobarbituric acid (TBA) test, a quantitative assay for the detection of malondialdehyde (MDA) and therefore lipid peroxidation, were used to determine the antioxidative properties of metronidazole after UV irradiation. Results clearly show that metronidazole has antioxidative properties in a cell-free environment, acting as a free radical scavenger. Simple skin lipid model: in the presence of 10, 100 and 500 microg mL(-1)metronidazole the MDA concentration was reduced by 25, 36 and 49%, respectively. Complex skin lipid system: in the presence of 100 and 500 microg mL(-1)metronidazole the MDA concentration was reduced by 19 and 34%, respectively. The results obtained in this study and from previous publications strongly suggest that metronidazole exhibits antioxidative effects via two mechanisms: decrease in ROS production through modulation of neutrophil activity and decrease in ROS concentration by exhibiting ROS scavenging properties. The remarkable clinical efficacy of metronidazole in the treatment of rosacea is probably due to its ability to decrease ROS via different mechanisms, thereby protecting skin components from induced damage. PMID- 17725857 TI - Effects of water-soluble low-molecular-weight beta-1, 3-D-glucan (branch beta-1, 6) isolated from Aureobasidium pullulans 1A1 strain black yeast on restraint stress in mice. AB - It is well known that different stress paradigms are able to rapidly induce corticosterone production and immune function through the activation of the hypothalamic-pituitary-adrenal axis. It has been reported that glucocorticoids suppress natural killer (NK) activity and interleukin (IL)-1 production and, on the other hand, that IL-1 and IL-6 stimulate the release of corticotrophin releasing-hormone from the rat hypothalamus. Moreover, it has been reported that IL-12 plays a central role in the initiation of cell-mediated immunity, directly and via its induction of interferon (IFN)-gamma and activation of NK cells. In this study, we examined the effects of water-soluble low-molecular-weight beta glucan isolated from Aureobasidium pullulans 1A1 strain on the corticosterone levels and immune function, such as NK activity and IL-6 and IL-12 production, using a restraint stress-induced mouse model. The water-soluble low-molecular weight beta-glucan at a dose of 50 or 100 mg kg(-1) inhibited the increases in the blood corticosterone level and the reduction of NK activity induced by restraint stress. Furthermore, the water-soluble low-molecular-weight beta-glucan (100 mg kg(-1)) prevented the reduction of IL-6 and IL-12 production by splenocytes caused by restraint stress. These findings suggest that the inhibitory actions of water-soluble low-molecular-weight beta-glucan on the increase in corticosterone level and reduction of NK activity induced by restraint stress may be associated with the abrogation of the IL-6 and IL-12 reduction caused by the stress. Thus, water-soluble low-molecularweight beta glucan may be an effective dietary supplement for the prevention of stress. PMID- 17725858 TI - Combined effect of total alkaloids from Feculae Bombycis and natural flavonoids on diabetes. AB - Both total alkaloids from Feculae Bombycis (TAFB) and natural flavonoids can inhibit alpha-glucosidase activity to depress the glucose level in blood. To investigate the cooperative effect of TAFB and flavonoids on blood glucose, we have studied their combined function compared with individual ingredients on enzymology, in-vitro and in-vivo. In the enzymological assay, the combination of TAFB and flavonoids showed more effective inhibition, compared with either TAFB or flavonoids alone, to alpha-glucosidase activity. In the everted intestine model in-vitro, the combined inhibition of starch hydrolysation and glucose transference to blood was much stronger than with separate components. In short term studies with normal and experimentally-induced diabetic mice in-vivo, the combination of TAFB and flavonoids also had a stronger suppressive effect on the postprandial elevation in blood glucose after oral administration. In long-term treatment to diabetic mice in-vivo, the compound prescription could depress not only the fasting blood glucose, but also the fasting blood total cholesterol. These results demonstrated that TAFB and flavonoids could inhibit alpha glucosidase activity cooperatively, which would successfully depress blood glucose level in the therapy of diabetes. PMID- 17725860 TI - Salutary effects of Corydalis yanhusuo extract on cardiac hypertrophy due to pressure overload in rats. AB - We have evaluated the effects of an alcohol extract from the rhizome of Corydalis yanhusuo W. T. (CY), a well-known traditional Chinese medicinal herb, on pressure overloaded cardiac hypertrophy induced by transverse abdominal aorta constriction (TAAC) in rats. Rats were given vehicle or CY extract (200 or 50 mg kg(-1) per day) from the second week after induction of pressure overload, for a period of 7 weeks. Haemodynamic parameters, relative heart weight and myocyte cross-sectional area were measured in each group. We also estimated left ventricular (LV) collagen volume fraction (CVF) using Masson trichrome staining, and type I collagen expression by Western blot assay. Chronic TAAC caused notable cardiac hypertrophy and heart dysfunction. Significant collagen deposition and greater type I collagen expression were found in model control rats. These changes were not significantly reversed after treatment with 50 mg kg(-1) CY, whereas 200 mgkg(-1) significantly improved heart function and prevented cardiac hypertrophy, with parallel reductions in myocardial fibrosis, as evidenced by reduced LV CVF and reduced levels of type I collagen. In conclusion, chronic treatment of rats with CY extract attenuated development of cardiac hypertrophy. PMID- 17725859 TI - Anti-inflammatory and analgesic activities of the ethanolic extracts from Zanthoxylum riedelianum (Rutaceae) leaves and stem bark. AB - We have evaluated the anti-inflammatory and analgesic properties of the leaves (LCE) and stem bark (BCE) crude extracts of Zanthoxylum riedelianum (Rutaceae). Different fractions of the stem bark extract (hexane, BCEH; dichloromethane, BCED; ethyl acetate, BCEE; and lyophilized aqueous residual, BCEW) were also investigated. We studied the effects of the extracts and fractions using the rat paw oedema test induced by carrageenan, dextran, histamine or nystatin; the mouse abdominal constriction test; the mouse hot-plate test (only for LCE and BCE); and the mouse formalin test. Both extracts and all BCE fractions displayed anti inflammatory activity in the carrageenan-induced oedema model, but not for dextran, histamine or nystatin. Considering the analgesic models, both extracts showed antinociceptive activity, but BCE was more active than LCE in models of central pain. All BCE fractions showed significant inhibition in the abdominal constriction test and in both phases of the formalin test. When BCED was submitted to phytochemical procedures it led to the isolation of six lignans (sesamin, methylpluviatolide, dimethylmatairesinol, piperitol-4(')-O (gamma),(gamma)-dimethylallyl ether, kaerophyllin and hinokinin), and a triterpene (lupeol). Inhibition of cyclooxygenase and its metabolites may have been involved in the mechanism of action of this plant, considering previous studies reporting the anti-inflammatory and analgesic activity for the identified lignans, as well as anti-inflammatory activity for lupeol. PMID- 17725861 TI - Gu Ling Pian, a traditional Chinese medicine, regulates function and OPG/RANKL synthesis of osteoblasts via the p38 MAPK pathway. AB - Osteoporosis is a common disease that makes bones prone to fracture and can affect both men and women. Many traditional Chinese medicine formulations have the potential effect of preventing osteoporosis. Gu Ling Pian (GLP), a traditional Chinese medicine formulation, comprised of tonifying kidney herbal medicines, has been demonstrated to prevent osteoporosis by increasing bone mineral density, however the exact mechanism has not yet been elucidated. Osteoprotegerin (OPG), a receptor activator of NF-kappaB (RANK), and RANK ligand (RANKL) play critical roles in bone remodelling by regulating the function of osteoclasts. In this study, we investigated the effect of GLP on osteoblasts, namely MG-63 cells. The cell proliferation and differentiation, synthesis of OPG/RANKL and p38 expression were tested on MG-63 cells exposed to serum from rats fed with GLP or not. The results showed that GLP significantly promoted MG 63 cell proliferation and differentiation. Upregulation of OPG and down regulation of RANKL at the protein and mRNA level were observed in GLP serum treated MG-63 cells using an enzyme-linked immunosorbent assay and real-time polymerase chain reaction. Further, treatment with GLP serum increased the level of p38 phosphorylation but did not affect the total p38 expression. These effects can be blocked by the p38 specific inhibitor SB203580. The results indicate that GLP can effectively promote the proliferation and differentiation of osteoblasts and regulate their OPG/RANKL expression, while the effects may be mediated via the p38 MAPK pathway. The findings suggest that GLP induces bone formation and may be beneficial for patients with osteoporosis. PMID- 17725862 TI - Separation and purification of saponins from Semen Ziziphus jujuba and their sedative and hypnotic effects. AB - Semen Ziziphus jujuba (SZJ) has long been used in Chinese traditional medicine for the treatment of anxiety and insomnia because of its effect of decreasing monoaminergic system activity; saponins are thought to be the main bioactive factors. To investigate the sedative and hypnotic effects of saponins from SZJ, silica gel column chromatography and thin-layer chromatography were used to purify the crude extract of total saponins from SZJ. High-performance liquid chromatography showed that saponins from SZJ comprised two components, compounds I and II. Animal tests were conducted using these two compounds to compare their sedative and hypnotic effects. Results showed that both compounds had a significant effect (P < 0.05, P < 0.01) on walking time compared with that of the control group. Compound I had a significant effect on coordinated movement (P < 0.05). Both compounds prolonged the suprathreshold barbiturate induced sleeping time (P < 0.05). The number of sleeping animals increased by 30% and 20% for compounds I and II, respectively, under the subthreshold dose of sodium barbital. PMID- 17725863 TI - Pressurized liquid extraction of organochlorine pesticides from certified solid materials. AB - In order to propose a versatile method to use in laboratories devoted to environmental analysis, a scheme for the determination of organochlorine pesticides from different solid matrices is evaluated. Pressurized liquid extraction is chosen as the sample preparation technique, followed by the purification of the extract by means of solid-phase extraction with Envi-carb cartridge (100 m(2)/g). Finally, the extracts are analyzed by programmed temperature vaporization (PTV)-gas chromatography (GC)-electron-capture detection and PTV-GC-mass spectrometry. The suitability of the method for the analysis of different matrices is determined by the extraction and analysis of four certified reference materials of solid matrices: CRM 804-050 (soil), SRM 1941b (organics in marine sediment), SRM 1944 (New York/New Jersey waterway sediment) and SRM 1649a (Urban Dust). Good statistical concordance between the results obtained and the certified or reference concentration are observed for most of the analyzed pesticides. PMID- 17725864 TI - Multiresidue determination of 77 pesticides in textiles by gas chromatography mass spectrometry. AB - A simple and efficient method for multiple determination of 77 pesticides, including one organonitrogen, eight carbamate, 12 pyrethroid, 26 organochloride, 30 organophosphorous compounds, in textiles is developed. Six representative textiles are chosen as test samples. Extraction using hexane-ethyl acetate (1:1) assisted by ultrasonic processor is carried out twice, followed by clean-up using solid-phase extraction on a florisil column. The final solution is analyzed using gas chromatography-mass spectrometry, and 77 pesticides are determined. This method is highly sensitive, selective, and reproducible, with a broad linear range and reliable accuracy. Six blank samples are spiked with 0.50 and 2.00 mg/kg of the 77 pesticides, and the corresponding recoveries are between 64.5% and 99.1%; the precisions range from 4.04% to 14.78%; and the minimum detection limits of this method are 0.02-0.20 mg/kg. PMID- 17725865 TI - Quantitative structure-property relationship study of retention time of some pesticides in gas chromatography. AB - A quantitative structure-property relationship (QSPR) study based on multiple linear regression (MLR) and artificial neural network (ANN) techniques is carried out to investigate the retention time behavior of some pesticides on the DB-5ms fused-silica column in gas chromatography. Five descriptors selected in the MLR model are: first component WHIM index (E1v), highest eigenvalue n.7 of burden matrix / weighted by atomic van der waals volume (BEHv7); average connectivity index Chi-2 (X2a), 3D-MoRSE signal 23 weighted by atomic Sanderson electronegativity (MoR23m); and principal moments of inertia B (PMIB). A 5-5-1 ANN is also generated to investigate the retention behavior of described pesticides using the same descriptors MLR model as inputs. The statistical parameters derived from MLR and ANN for all molecules are: correlation coefficient (R)(MLR) = 0.929, standard errors (SE)(MLR) = 3.452, R(ANN) = 0.943, and SE(ANN) = 3.112. The mean of relative errors between the MLR and ANN calculated and the experimental values of the retention times for the prediction set are 13.8% and 9.04%, respectively. The correlation coefficient and standard error of ANN model compared with MLR models showed the superiority of ANNs over regression models. This is partly due to the fact that ANN considers the interaction between different parameters as well as nonlinear relation. PMID- 17725866 TI - Determination of sodium monofluoroacetate (1080) in biological samples as its 4 bromomethyl-7-methoxycoumarin derivative by RP-HPLC. AB - A high-performance liquid chromatography (HPLC) method with fluorescence detection is described for the determination of sodium monofluoroacetate (MFA-Na) in biological samples. 4-Bromomethyl-7-methoxycoumarin is used as a derivatization reagent and reacted with MFA-Na to form 7-methoxy-4 methylenecoumarin monofluoroacetate for HPLC analysis. Chromatographic separation is performed on a Hewlett Packard RP-18 column using methanol-water (60:40, v/v) as the mobile phase. A fluorescent detector is employed with the excitation and emission wavelengths as 319 nm and 390 nm, respectively. The novel method yields a good linear relationship when the concentration of MFA-Na is within 1 and 500 nmol/mL (r = 0.9996). The detection limit is 50 pmol/mL. The established method is applied to determine MFA-Na in biological samples. The recovery rates of MFA Na are between 81% and 88%, and the relative standard deviations are less than 5%. The method shows good sensitivity and selectivity for the determination of MFA-Na in biological samples. PMID- 17725867 TI - Development and validation of a simple and rapid HPLC method for the quantitative determination of voriconazole in rat and beagle dog plasma. AB - A simple and rapid high-performance liquid chromatographic method with UV detection is developed and validated to determine the concentration of voriconazole in rat and beagle dog plasma. After protein precipitation using acetonitrile, the supernatant solution is chromatographed on a Diamonsil C(18) column (250 x 4.6-mm i.d., 5 microm). The mobile phase used is a combination of acetonitrile-water-acetic acid (55:45:0.25, v/v/v) with a pH of 4.0. Detection is achieved by a UV detector monitored at a wavelength of 256 nm. The matrix calibration curves are obtained both in the concentration range of 0.10-50.0 microg/mL in rat and beagle dog plasma, with the lower limit of quantitation of 0.10 microg/mL. The intra- and inter-assay precisions in terms of % relative standard deviation are lower than 8.6% and 6.0% in rat and beagle dog plasma, respectively. The accuracy in terms of % relative error ranged from -0.5% to 8.0% and -0.5% to 6.0% in rat and beagle dog plasma, respectively. This validated method is successfully applied to determine the concentration of voriconazole in plasma after intravenous administration of 36 mg/kg voriconazole to rats and 10 mg/kg voriconazole to beagle dogs, respectively. PMID- 17725868 TI - Nylon-6 capillary-channeled polymer fibers as a stationary phase for the mixed mode ion exchange/reversed-phase chromatography separation of proteins. AB - Capillary-channeled polymer (C-CP) fibers extruded from nylon-6 are used as the stationary phase for the ion-exchange/reversed-phase mixed-mode chromatographic separation of a three protein mixture. The nylon-6 C-CP fibers are packed collinearly in a 250 x 1.5-mm i.d. column with an interstitial fraction of approximately 0.6. The effects of four displacing salts at three different pHs are studied with regards to protein retention time, peak width, selectivity, and resolution for a synthetic mixture consisting of myoglobin, ribonuclease A, and lysozyme to determine the optimum mobile phase conditions. The net charge model is found to be inadequate in fully explaining the retention behavior, as the proteins are retained by anion and cation-exchange interactions, as well as hydrophobic interactions with the stationary phase. It is found that pH and displacing salt strength had a significant influence on the retention properties and resolution of the proteins. PMID- 17725869 TI - Development of a gas chromatographic test for the quantitation of the biomarker 2 butoxyacetic acid in urine samples. AB - An accurate and precise method is developed and evaluated for the detection and quantitation of 2-butoxyacetic acid (2-BAA), a metabolite and biomarker for human exposure to 2-butoxyethanol. The solvent 2-butoxyethanol (2-BE) is extensively used in various industrial and domestic applications, and it is a health concern owing to its toxicity. Sample preparation consists of liquid-liquid extraction (LLE) of urine, then esterification of 2-BAA to produce the ethyl ester analog. The gas chromatographic conditions utilize a dimethyl polysiloxane phase (HP-1) capillary column and a mass spectrometer (MS) for detection of the analyte. Validation of this method includes a recovery study using fortified urine samples, which demonstrated good accuracy and precision; recovery varied between 100% and 102% of theory, with relative standard deviations of replicate samples at 2.8% and less. The detection limit of this method ranges from 0.005 to 0.015 microg/mL equivalent level of 2-BAA in urine. PMID- 17725870 TI - Determination of volatile compounds in cider spirits by gas chromatography with direct injection. AB - Two analytical methods based on gas chromatography with direct injection are described for the quantitative analysis of volatile compounds (acetals, aldehydes, esters, alcohols, and volatile phenols) in cider brandies. Analytes were divided into major, 15, and minor volatile, 24, compounds depending on their usual concentration in samples. Parameters usually tested for method validation are evaluated. Correlation coefficients are calculated to estimate linearity, obtaining values higher than 0.999. Detection limits range between 0.325 mg/L (1 propanol) and 1.663 mg/L (methanol) among the major volatile compounds and between 0.086 mg/L (ethyl 2-methylbutyrate) and 0.332 mg/L (ethyl tetradecanoate) among the minor volatiles. Mean recoveries ranged between 109% (ethyl lactate) and 95% (1-butanol) for major volatiles and between 109% (1-octen-3-ol) and 94% (ethyl 2-methylbutyrate) for minor volatiles, thus confirming the accuracy of both methods. Reproducibility for major volatiles is < 5.4% (furfural) in all cases and < 9.6% (hexyl acetate) for minor volatiles. Moreover, the accuracy of the methods is evaluated by analyzing a certified whisky and five samples from interlaboratory assays, generally obtaining results in accordance with previous values. PMID- 17725871 TI - Biological and chemical detections in adsorbent layer for monitoring microbial production of primycin. AB - Primycin is a macrolide antibiotic complex produced in microbiological fermentation processes. The microbial production of primycin requires an in process analytical method suitable for monitoring the level of the active agents. In this paper, a method fulfilling the described requirement is presented. This method consists of a simple, efficacious extraction step, an instrumental sample application followed by a high-performance thin-layer chromatographic separation in relatively short time and a quantitative chromatogram evaluation. A dipping technique, in a solution containing sulfuric acid followed by heating at 120 degrees C, is used for chromogen formation, resulting in an absorption maximum at 290 nm. A progress diagram of the fermentation obtained by this technique is compared with one obtained by a microbiological agar diffusion method. The bioautographic evaluation of the active spots in the chromatogram are also presented. By our TLC method, the group of the active primycin components in the fermentation broth and by-products formed during the fermentation can be well separated. The relative intensities of the different TLC spots provide some information on the formation of the active components. PMID- 17725872 TI - Validation of geosmin and 2-methyl-i-borneol analysis by CLSA-GC-FID method to obtain ISO-17025 accreditation. AB - A study of the accreditation process using closed loop stripping analysis (CLSA) gas chromatography (GC)-flame ionization detection (FID) methodology for the analysis of geosmin and 2-methyl-i-borneol (MIB) is performed, completing the instrumental validation process. Quality parameters, such as the linearity ranges, repeatability and reproducibility, efficiencies, matrix effects, and interference, are presented. The experimental work is completed with a study of the associated uncertainty using a "Bottom-up Approach Method" and a short description of a control-protocol for preserving the validation conditions as a method of quality assurance protocol. The results show that CLSA-GC-FID-MS is a very good tool for the analysis of geosmin and MIB at a low level threshold, and the working range obtained is 10-400 ppt (ng/L) for geosmin and 15-400 ppt for MIB, respectively, in both drinking and natural waters. Uncertainty was approximately 16% for both compounds; good reproducibility with precision below 10% and bias between 85-90% for the three matrices considered are obtained. PMID- 17725873 TI - Thin-layer chromatography of alkaloids on cyanopropyl bonded stationary phases. Part I. AB - Selected alkaloids are chromatographed on cyanopropyl-silica thin layers using various nonaqueous and aqueous eluents. Because of the strong retention of these basic compounds, nonaqueous eluents containing medium polar diluents, strongly polar modifiers, and silanol blockers (ammonia or diethylamine) are required for separation. Likewise, aqueous eluents containing modifiers (acetonitrile, methanol, and tetrahydrofuran), buffered aqueous solutions at pH 2-8, ion-pair reagents [octane sulfonic acid sodium salt, sodium dodecyl sulphate, and bis-(2 ethylhexyl)phosphoric acid], or silanol blockers (ammonia, tetrabutyl ammonium chloride, and diethyl amine) are investigated. The separation selectivity as well as spot symmetry and efficiency system in the applied eluent systems are analyzed. The most selective and efficient systems are used in two-dimensional separations of isoquinoline alkaloids' mixture and the plant extracts Chelidonium majus, Fumaria officinalis, and Glaucium flavum. Two-dimensional thin-layer chromatography on cyanopropyl layer with diode array detection densitometry enables the separation and identification of some alkaloids in plant extracts. PMID- 17725874 TI - Identification and quantification of diethylene glycol in pharmaceuticals implicated in poisoning epidemics: an historical laboratory perspective. AB - Over the last several decades, mass poisonings of diethylene glycol (DEG), usually ingested as an unintended component of pharmaceutical preparations, have occurred. In order to promptly halt the rise in deaths due to ingestion of these pharmaceuticals, laboratory analysis has often been employed to identify and quantify the etiologic agent after the medications have been tentatively implicated. Over the past 15 years, the Centers for Disease Control and Prevention has been involved in identifying DEG in implicated pharmaceutical products during three poisoning epidemics that occurred in Nigeria (1990), Haiti (1995), and, most recently, in Panama (2006). In each case, the timeliness of the identification was paramount in reducing the mortality involved in these mass poisonings. Using state-of-the-art analytical technology, we were able to provide initial identification of DEG within 24 h of receiving samples for each epidemic, allowing a timely public health response. However, over the past 15 years, the analytical instrumentation available and the laboratory responses undertaken have changed. In addition, the type of information and the degree of confirmation of results requested during each epidemic varied based upon the number of individuals involved and the political tenor involved with the outbreak. We describe our historical approach to identifying and quantifying DEG during each of these outbreaks. Furthermore, the reoccurrence of outbreaks has prompted us to establish standard technology to use in potential future outbreaks to allow an even more timely response. This methodology includes the development of biomarkers of DEG exposure, which would be extremely useful in instances where pharmaceuticals are not clearly implicated. PMID- 17725875 TI - Rapid and unambiguous identification of melamine in contaminated pet food based on mass spectrometry with four degrees of confirmation. AB - A method for analyzing pet food without sample processing is described for rapid identification of melamine based on mass spectrometry (MS) using soft ionization by direct analysis in real time (DART) to provide accurate measurement of mass and isotope-peak intensities, in-source collisionally activated dissociation (CAD) fragmentation, and determination of active hydrogens. Usually, MS analyses based on other than electron ionization (EI) spectra can be suspect because of the limited amount of information provided by a single mass spectral peak (or very few peaks). In such cases, additional degrees of confirmation are desirable to increase confidence in the experimental results. Chromatographic retention time can provide a degree of confidence; however, this requires time and, in some cases, detailed sample processing. Currently, the United States Food and Drug Administration uses a gas chromatography-EI-MS technique for the determination of melamine in pet food that involves sample extraction and derivatization prior to a lengthy chromatographic separation. In the method described here, identification is also confirmed through a determination of the number of active hydrogen atoms in the analyte molecule achieved by hydrogen/deuterium (H/D) exchange by treatment with deuterium oxide (D2O) at the initial stage of analysis. Cross-correlation of these four experimental data provides an unambiguous identification of melamine in contaminated pet food without the need for any sample preparation or chromatography. Limits of detection and the validity of the H/D exchange method as a confirmatory technique are also presented. PMID- 17725877 TI - Toxicological screening in urine: comparison of two automated HPLC screening systems, toxicological identification system (TOX.I.S.*) versus REMEDI-HS. AB - In this paper, the comparison of two automated high-performance liquid chromatography (HPLC) screening systems, a newly developed toxicological identification system (TOX.I.S.) versus the commercially available Remedi-HS (Bio Rad), is presented. Urine samples from 405 cases screened positive for amphetamines, cocaine, and opiates by immunological assays and confirmed by GC-MS were analyzed with both systems. In more than 80% (TOX.I.S.) and 78% (Remedi-HS) of the cases (except for cocaine), the results obtained by both HPLC methods showed agreement with the earlier obtained results by immunoassay prescreening and gas chromatography-mass spectrometry (GC-MS). The evaluation showed that both automated HPLC methods led to comparable results and can be used alternatively. As the confirmation results for cocaine were rather poor (45% TOX.I.S., 54% Remedi-HS) in comparison to GC-MS, the TOX.I.S. was further optimized for the detection of the cocaine metabolite benzoylecgonine (BEC). The BEC method improved the detectability of BEC from 45% to 80%. Besides confirmation screening, the use of both systems in cases of acute intoxications was investigated. Information about basic compounds was obtained from urine screening by both systems, which therefore were useful as complementary techniques in the toxicological laboratory. The TOX.I.S. offers advantages such as common equipment, modern software, and higher versatility with the opportunity to establish additional methods in the system. PMID- 17725876 TI - Simultaneous determination of nontricyclic antidepressants in human plasma by solid-phase microextraction and liquid chromatography (SPME-LC). AB - A sensitive, selective, and reproducible solid-phase microextraction and liquid chromatographic (SPME-LC) method for simultaneous determination of mirtazapine, citalopram, paroxetine, fluoxetine, and sertraline in human plasma was developed, validated, and further applied to analyze plasma samples obtained from patients with depression. Important factors in the optimization of SPME efficiency are discussed, including the fiber coating, extraction time, pH, ionic strength, influence of plasma proteins, and desorption conditions. The limit of quantitation of the nontricyclic antidepressants in plasma varied from 25 to 50 ng/mL with a coefficient of variation lower than 5%. The response of the SPME-LC method for most of the drugs was linear over a dynamic range of 50 to 500 ng/mL, with all of them having correlation coefficients greater than 0.9970. The performance of the SPME-LC method allowed the nontricyclic antidepressants analyses in therapeutic levels. PMID- 17725878 TI - The postmortem distribution of vardenafil (Levitra) in an aviation accident victim with an unusually high blood concentration. AB - Vardenafil (Levitra) is one of the most widely prescribed treatments for erectile dysfunction. This report presents a rapid and reliable method for the identification and quantification of vardenafil in postmortem fluids and tissues, applies this method to a postmortem case, and describes the distribution of vardenafil in various fluids and tissues. This procedure utilizes sildenafil-d8, which is structurally closely related to vardenafil, as an internal standard for more accurate and reliable quantitation. The method incorporates solid-phase extraction and liquid chromatography-tandem mass spectrometry (MS) and MS-MS-MS utilizing an atmospheric pressure chemical ionization ion trap MS in the positive chemical ionization mode. Solid-phase extraction proved to be exceptionally efficient providing recoveries that ranged from 94% to 97%. The limit of detection for vardenafil was determined to be 0.19 ng/mL. The linear dynamic range for this compound was 0.39-200 ng/mL. This method was successfully applied to postmortem fluid and tissue specimens obtained from an aviation accident victim. The distribution of vardenafil in various fluids and tissues and the unusually high concentration of vardenafil in the victim's blood are examined. PMID- 17725879 TI - Quantification of eight new antidepressants and five of their active metabolites in whole blood by high-performance liquid chromatography-tandem mass spectrometry. AB - A liquid chromatography-tandem mass spectrometry method is described for the blood determination of selective serotonin reuptake inhibitors (fluoxetine, paroxetine, sertraline, fluvoxamine, and citalopram), serotonin noradrenaline reuptake inhibitors (milnacipram and venlafaxine), a noradrenergic and specific serotoninergic antidepressant (mirtazapine) and five of their active metabolites (norfluoxetine, desmethylcitalopram, didesmethylcitalopram, desmethylvenlafaxine, and desmethylmirtazapine). After a liquid-liquid extraction from blood, the compounds and the internal standard (methylrisperidone) were eluted on a XTerra RP18 column with a gradient of acetonitrile/ammonium formate buffer 4 mmol/L pH 3.2. They were then detected by electrospray ionization mass spectrometry with multiple reaction monitoring mode. The calibration curves were linear over the range 5-500 ng/mL (20-2000 ng/mL for venlafaxine and desmethylvenlafaxine). The limit of quantification was set at 5 ng/mL for each compound (except for venlafaxine and desmethylvenlafaxine: 20 ng/mL). The bias were lower than 12%. Intraday and interday precisions, expressed as variation coefficient, were lower than 11%. The extraction recoveries were between 70 and 90% except for desmethylmirtazapine, desmethylvenlafaxine, milnacipram, and didesmethylcitalopram. This specific and sensitive method allows management of intoxication and is suitable for the routine determination of antidepressants in forensic investigations. PMID- 17725880 TI - Quantitative endogenous formate analysis in plasma using headspace gas chromatography without a headspace analyzer. AB - The objective was to develop a simple routine method for quantitative measurement of endogenous formic acid in plasma and whole blood using headspace gas chromatography-flame ionization detection. (GC-FID). Two-hundred microliters of sample was placed in a 1-mL glass vial. Fifty microliters of aqueous ethanol (10%) was added as an internal standard and a derivatizing agent. Ethylformate formation was enhanced by addition of 200 microL concentrated sulfuric acid as a catalyst. The vials were then sealed immediately and placed in a water bath for 15 min at 60 degrees C. One milliliter of this headspace gas was siphoned using a gas-tight syringe and injected into a GC-FID fitted with a capillary column. Ethanol eluted at approximately 3.0 min, and ethylformate eluted around 4.7 min. The limit of quantitation for ethylformate was 0.026 mmol/L, and the limit of detection was 0.020 mmol/L. Imprecisions for spiked plasma samples at 0.25 and 1 mmol/L were 10% and 9%, respectively and recoveries were at 100% and 108%, respectively. A simple, reliable, and highly specific headspace analysis method for quantifying endogenous formate without the use of a headspace analyzer was developed. This method enables the routine clinical analysis of formate in plasma and whole blood samples. PMID- 17725881 TI - Immunochromatographic analysis of hippuric acid in urine. AB - Toluene, a clear, colorless liquid with a distinctive smell, is the most commonly used industrial organic solvent. The adverse effects of chronic toluene exposure have been reported. The abuse of volatile substances is practiced mainly by adolescents and young adults. Chronic toluene abuse causes permanent changes in brain structure correlated with brain dysfunction; therefore, it is important to monitor the level of toluene exposure to prevent neurological damages. In this study, immunochromatographic analysis was performed to measure a level of the exposed toluene easily and accurately in urine. Inhaled toluene is metabolized to hippuric acid (HA) in the liver and secreted in urine. Therefore, the monoclonal antibodies against HA were generated and characterized by indirect competitive ELISA. The sensitivity was then monitored in order to adjust the cutoff concentration to 2 mg of HA/mL of urine. Using these monoclonal antibodies as raw materials, the immunochromatographic device was manufactured with the lateral flow system. The clinical studies were performed with suspected users' urine samples, and the results were confirmed by high-performance liquid chromatography. PMID- 17725882 TI - Field-test of a date-rape drug detection device. AB - Drink Safe Technology Version 1.2 is an inexpensive color-change reagent test marketed internationally for use by consumers in settings such as a night club to detect potentially incapacitating concentrations of gamma-hydroxybutyric acid (GHB) and ketamine in beverages. The objective of this study was to compare product performance in the laboratory and performance in the hands of consumers in the field. Product performance in the laboratory adhered to the protocol defined by the manufacturer. Product performance in the hands of consumers in field settings allowed browsing participants to pipette an aliquot of their own drinks into randomly coded vials containing authentic drugs, or pure water, so as to yield the same concentrations of GHB or ketamine specified in the manufacturer defined protocol, or blanks. Consumers were to proceed according to the directions printed on the product, and to record their results on a card with a code corresponding with the vial to which they had added an aliquot of their beverage. Diagnostic performance was calculated using two-way analysis. In the laboratory, Drink Safe Technology Version 1.2 reliably detected GHB and ketamine at concentrations specified by the manufacturer's protocol. The reactive color change denoting a positive test for GHB was rapid, but a positive test for ketamine required substantially more time to resolve. Nonetheless, test accuracy following the manufacturer's protocol in the laboratory was 100%. In the field, based on 101 paired-test results recorded by consumers, the test efficiency was 65.1%, sensitivity 50%, and specificity 91.6%. The product performed much better in the laboratory than it did in the hand of consumers in the field. There seems to be considerable potential for consumers to misinterpret a test result. The potential for consumers to record a false-negative test result for a spiked drink is cause for concern. PMID- 17725883 TI - Simultaneous determination of multiple drugs of abuse and relevant metabolites in urine by LC-MS-MS. AB - A method was developed for the quantitative analysis of 30 drugs of abuse and their metabolites in urine, including opiates, barbiturates, amphetamines, cocaine, cannabinoids, phencyclidine, methadone, and benzodiazepines. This method uses solid-phase extraction (SPE) on an Oasis HLB column followed by liquid chromatography-tandem mass spectrometry. Analytes were quantified by multiple reaction monitoring with the deuterated analogues as internal standards, using an atmospheric pressure ionization-electrospray interface. The method was validated by examining specificity, precision, accuracy, linearity, recovery, reproducibility, and detection limits. The limits of detection ranged from 9 pg/mL to 2.29 ng/mL in urine depending on the analyte. The SPE procedure was automated on a RapidTrace workstation to increase analytical throughput, and the results obtained via automated SPE were compared to those obtained by manual SPE to examine carryover effect, precision, accuracy, recovery, and reproducibility. To evaluate method performance, 108 urine samples were collected anonymously and tested for the presence of these drugs. PMID- 17725884 TI - Simultaneous analysis of 14 benzodiazepines in oral fluid by solid-phase extraction and LC-MS-MS. AB - A simple and rapid procedure for the simultaneous screening of 14 benzodiazepines in oral fluid is presented. The procedure involves a solid-phase extraction followed by liquid chromatography-tandem mass spectrometry (LC-MS-MS). The target compounds include diazepam, oxazepam, temazepam, nordiazepam, lorazepam, chlordiazepoxide, alprazolam, alpha-hydroxyalprazolam, desalkylflurazepam, hydroxyethylflurazepam, clonazepam, 7-aminoclonazepam, flunitrazepam, and 7 aminoflunitrazepam. Oral fluid was obtained using a simple device that collects approximately 0.4 mL of oral fluid and dilutes it with 0.8 mL of preservative. The oral fluid sample preparation involves a solid-phase extraction on a Varian Bond Elut cartridge. Quantitation was performed by LC-MS-MS using nordiazepam d(5) as the internal standard. The extraction efficiency exceeded 83% for all compounds except for 7-aminoclonazepam, which had a recovery of 55%. The limits of quantitation ranged from 0.1 ng/mL to 1.0 ng/mL in the multiple reaction monitoring mode. This method was used to confirm 41 patients that screened positive using the OraSure Technologies Benzodiazepine Intercept MICRO-PLATE Enzyme Immunoassay kit. All screened-positive patients were positive for at least one of the analyzed benzodiazepines, thus showing that this method is suitable for confirmation of the Intercept Benzodiazepine assay. PMID- 17725885 TI - Development and GC-MS validation of a highly sensitive recombinant G6PDH-based homogeneous immunoassay for the detection of buprenorphine and norbuprenorphine in urine. AB - Buprenorphine is now increasingly prescribed as an alternative to methadone for the treatment of heroin addiction. Because of its potency (dosage usages from 0.2 mg to 8 mg), the drug concentrations in body fluids are normally very low. Here, we report the first recombinant glucose-6-phosphate dehydrogenase (G6PDH)-based homogeneous immunoassay (EMIT-type assay) for free buprenorphine and free norbuprenorphine in urine. The antibody used in this assay cross-reacts nearly identically with buprenorphine and norbuprenorphine and, at the same time, has less than 1% cross-reactivity with a wide range of commonly prescribed opiates, particularly those structurally related compounds such as morphine, codeine, and dihydrocodeine. More importantly, this assay has a low detection limit of 1 ng/mL for buprenorphine or norbuprenorphine. Further evaluation of this technique using gas chromatography-mass spectrometry (GC-MS) of authentic urine samples demonstrated that the accuracy of the assay is greater than 95%. Because this assay is designed to measure the free drugs in urine, it resulted in simplification for GC-MS or liquid chromatography-MS confirmation methods that did not require urine hydrolysis before solid-phase or liquid-liquid extraction. PMID- 17725886 TI - Determination of thiocyanate in plasma by ion chromatography and ultraviolet detection. AB - A specific and sensitive rapid high-performance liquid chromatographic method has been developed for determination of thiocyanate (SCN-) in plasma. This method is based on anion exchange chromatography after a simple ultrafiltration of plasma diluted in water. The detection of SCN- is carried out in ultraviolet (lambda = 210 nm). The proposed method is linear in the range 1-30 mg/L. Intra-assay and interassay accuracy and precision were maintained within the designated limit (< 20%). The total recovery of SCN- varied between 97 and 103.9%. The method described should be useful for clinical medicine. Moreover, this method was applied to the analysis of SCN- plasma in deceased subjects, within the context of fire, and could be of interest in forensic science as a useful additional measurement tool for cyanide determination in blood. PMID- 17725887 TI - Microwave-assisted extraction and HPLC-DAD determination of drugs of abuse in human plasma. AB - A sample preparation procedure using microwave energy is proposed for the determination of morphine, 6-acetylmorphine, codeine, cocaine, cocaethylene, benzoylecgonine, methadone, and 2-ethylene-1,5-dimethyl-3,3-diphenylpyrrolidine in human plasma. A screening asymmetrical factorial design was used to identify the most suitable extraction conditions as regards solvent, temperature, and extraction time. The target drugs were quantified by high-performance liquid chromatography with diode-array detection. The use of microwave energy was found to reduce solvent consumption and extraction time compared with solid-phase extraction. The detector response was linear over the drug concentration range of 0.05-2.0 microg/mL in human plasma. The precision and accuracy were good, with values less than 8% and 7%, respectively. Drug recoveries from spiked samples ranged from 69 to 81%. The proposed method was successfully applied to a number of forensic cases. PMID- 17725888 TI - Method for quantification of opioids and their metabolites in autopsy blood by liquid chromatography-tandem mass spectrometry. AB - A method using liquid chromatography-electrospray ionization-tandem mass spectrometry was developed and validated for the determination of morphine, codeine, hydromorphone, dihydrocodeine, oxycodone, buprenorphine, and naloxone with their metabolites morphine-3-glucuronide, morphine-6-glucuronide, normorphine, 6-acetylmorphine, 6-acetylcodeine, codeine-6-glucuronide, norcodeine, hydromorphine-3-glucuronide, dihydrocodeine-6-glucuronide, dihydromorphine, dihydromorphine-3-glucuronide, dihydromorphine-6-glucuronide, oxymorphone, norbuprenorphine, buprenorphine-3-glucuronide, norbuprenorphine-3 glucuronide, and naloxone-3-glucuronide in human whole blood. Polar metabolites (glucuronides) and other analytes were extracted by SPE using Bond Elut C18. Chromatographic separation was performed on a Phenomenex Synergi reversed-phase column with gradient elution based on a mobile phase consisting of 10mM ammonium formate adjusted to pH 3 and acetonitrile. Intraday and interday precision for all analytes were between 0.6% and 13.8%, and recoveries were between 80.3% and 101.4%. Calibration curves were linear for all analytes over the concentration range 5-400 ng/mL, and correlation coefficients (R(2)) were better than 0.999. Limits of detection and quantitation were 0.16-1.2 ng/mL and 0.5-4.09 ng/mL, respectively. The method described consolidates previous work on opioids and their metabolites published in the literature and is the first to include the detection of naloxone-3-glucuronide. The method has been applied in routine postmortem cases after opiate overdose with the threefold purpose of providing interpretive information on the cause and type of death (rapid, sub-acute, or delayed death) and to distinguish heroin, morphine, and codeine users. PMID- 17725889 TI - The distribution of fluoxetine in human fluids and tissues. AB - Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that was introduced in 1986. Certain side effects of this medication-drowsiness, dizziness, abnormal vision, diarrhea, and headache-could affect pilot performance and become a factor in an aviation accident. Our laboratory has determined the distribution of fluoxetine and its desmethyl metabolite, norfluoxetine, in various postmortem tissues and fluids from 10 fatal aviation accident cases. When available, 11 specimen types were analyzed for each case, including blood, urine, vitreous humor, bile, liver, kidney, skeletal muscle, lung, spleen, heart muscle, and brain. Blood fluoxetine concentrations in these 10 cases ranged from 21 to 1480 ng/mL. The distribution coefficients for both fluoxetine and norfluoxetine, expressed as specimen/blood ratios, were determined. The distribution coefficients for fluoxetine were determined to be 0.9 +/- 0.4 for urine, 0.10 +/- 0.03 for vitreous humor, 9 +/- 1 for bile, 38 +/- 10 for liver, 60 +/- 17 for lung, 9 +/- 3 for kidney, 20 +/- 5 for spleen, 2.2 +/- 0.3 for muscle, 15 +/- 3 for brain, and 10 +/- 2 for heart. To our knowledge, this is the first report presenting the distribution of fluoxetine in humans at therapeutic concentrations. PMID- 17725890 TI - Domestic abuse of the European rave drug prolintane. AB - Prolintane is a sympathomimetic amine with pharmacologic properties similar to d amphetamine. Side effects include insomnia, nervousness, and irritability. Overdoses of prolintane may cause hallucinations, psychosis, and death. The drug is commonly prescribed in Africa, Australia, and Europe but is not available in the United States. This manuscript reports the first medically documented cases of prolintane abuse in the United States. In the first, a 34-year-old male presented to the emergency department confused, agitated, and unable to follow commands. Initial drug and alcohol screens were negative, but analysis by gas chromatography-mass spectrometry (GC-MS) indicated the presence of amitriptyline, nortriptyline, nicotine, and prolintane. The second patient, a healthy 26-year old female, presented to the emergency department after intrauterine fetal death and spontaneous delivery. GC-MS revealed the presence of multiple drugs, including cannabinoids, cocaine, nicotine, hydrocodone, and prolintane. The medical and scientific communities should be aware of the potential for prolintane abuse because it may cause symptoms similar to those of the amphetamines but is not likely to be detected by a routine urine drug screen. PMID- 17725891 TI - Comments on "Incomplete recovery of prescription opioids in urine using enzymatic hydrolysis of glucuronide metabolites". PMID- 17725892 TI - [Unused organ donor potential in Denmark]. PMID- 17725893 TI - [Clinical trial registration: looking back and moving ahead]. PMID- 17725894 TI - [Enhanced external counterpulsation. Evidence of effect on patients suffering from angina pectoris and for whom revascularisation is not possible]. AB - Enhanced external counterpulsation (EECP) is a non-invasive therapy for patients suffering from angina pectoris and for whom revascularisation is not possible. A standard EECP treatment comprises 35 hours over 7 weeks. Cuffs wrapped around the lower extremities and the hips are inflated with air in each diastole and deflated instantly at onset of systole. EECP has a long lasting effect on angina pectoris. Several studies using different methods of assessment with objective blinded methods, have shown that EECP-therapy reduces the ischemic area of the left ventricle. PMID- 17725895 TI - [No effect of calcium supplementation on bone mineral density in children. Survey of a Cochrane review]. PMID- 17725896 TI - [Ventricular aspiration]. PMID- 17725897 TI - [Functional magnetic resonance imaging in multiple sclerosis]. AB - The use of functional magnetic resonance imaging (fMRI) in multiple sclerosis (MS) is reviewed. fMRI is an efficient method to map brain activity non invasively and has shown that adaptive cortical changes take place as a consequence of demyelination and tissue loss in MS. These changes may help to maintain normal function in the course of MS, and to some extent they might explain the moderate correlation between conventional MRI findings and disability. fMRI can provide information about brain plasticity and thus improve our understanding of the disease. PMID- 17725898 TI - [General practitioners' job satisfaction]. AB - INTRODUCTION: The aim of the study was to assess the level of job satisfaction among Danish general practitioners (GPs). MATERIALS AND METHODS: A questionnaire on job satisfaction and sociodemography was sent to all 458 registered GPs in the County of Aarhus, Denmark. RESULTS: A total of 379 (83.5%) GPs participated. Danish GPs have a high level of job satisfaction. They were most satisfied with colleagues and fellow workers, amount of responsibility and freedom to choose their own method of working, and they were least satisfied with remuneration and hours of work. Longer working hours were associated with lower job satisfaction. Furthermore, GPs with low job satisfaction wanted to retire earlier. There was no association between job satisfaction and the number of practice staff. One in every twenty (6%) GPs would not repeat the same career choice again. Apart from their remuneration, Danish GPs' job satisfaction was higher than that of their Norwegian and British colleagues. CONCLUSION: Overall job satisfaction among Danish GPs was high, also compared with foreign countries. Low job satisfaction was associated with wanting to retire early, implying that a high level of job satisfaction is important for GP retention. Shorter working hour was associated with higher job satisfaction. PMID- 17725899 TI - [Social inequality in the burden of disease]. AB - INTRODUCTION: Social inequality in health status is apparent in different life expectancy as well as expected lifetime with illness. The purpose of the study was to estimate the difference in expected lifetime with cancer, cardiovascular diseases and diseases of the musculoskeletal system between Danes with high and low educational levels. MATERIALS AND METHODS: The study was based on data from the Danish Health Interview Survey in 2000 and registered data on education and mortality in the period 1995-1999. Expected lifetime with and without long standing, limiting illness based on observed data was compared with expected lifetime with and without long-standing, limiting illness after elimination of specific diseases and causes of death. The expected lifetime for persons with high and low educational levels between the age of 30 and 75 with and without illness was compared. RESULTS: Cancer contributes by 0.3 years to the difference in partial life expectancy (age 30-75) between persons with high and low educational levels. Cardiovascular diseases cause men with low educational levels a loss of 0.6 life years and women 0.4 life years compared to men and women with high educational levels. Because of co-morbidity elimination of cancer would increase social inequality in expected lifetime with illness. The same was seen for women if cardiovascular diseases were eliminated. If diseases of the musculoskeletal system were eliminated, the difference in expected lifetime without long-standing, limiting illness from age 30 to 75 between persons with high and low educational levels would be reduced by 1.2 years. CONCLUSION: Social inequality in life expectancy would be reduced by the elimination of cancer and cardiovascular diseases. Socially disadvantaged suffer from the largest burden of disease. PMID- 17725900 TI - [Survival in patients with HIV infection]. AB - It has been difficult to measure the median survival of HIV-infected patients by comparing selected HIV samples and control groups. Data from the Danish HIV Cohort Study combined with the Central Registration System has made it possible to accurately compare the survival of HIV-infected persons and uninfected persons. In 2000 to 2005, the median remaining lifetime at age 25 years in the general population was 51 years and 39 years for HIV-infected persons without hepatitis C virus infection. In conclusion, persons with HIV infection have a good, albeit far from normal, life expectancy. PMID- 17725901 TI - [Development in violence in Odense City from 1991-2002]. AB - The study included 14,316 consecutive victims of violence registered by Odense University Hospital and/or the Institute of Forensic Medicine, University of Southern Denmark from 1991-2002. The incidence rate was 9.9 and 3.4 per 1,000 population/year for males and females respectively. The incidence rate for males decreased during the period of the study. The proportion of less serious lesions increased and the proportion of potential severe lesions such as bone fractures and deep lesions decreased during the period of the study. The proportion of patients with injuries from knives or firearms did not change during the period of the study. PMID- 17725902 TI - [Organ donation from alcohol and opioid-abusing patient]. AB - A case of a 37-year old obese patient with alcohol, sedative and opioid abuse as well as previous admissions with chest pain is presented. The patient suffered from a large subarachnoid haemorrhage and the clinical diagnosis of brain death was made. He had substantial signs of organ failure. The patient was registered as a potential organ donor in the Danish Registry for Organ Donation, and his heart and kidneys were donated. Considering all brain dead patients as potential organ donors is important. PMID- 17725903 TI - [Hemorrhagic Rift Valley fever]. AB - A case of fatal hemorrhagic Rift Valley fever during an epidemic in Kenya's North Eastern Province in January 2007 is described. PMID- 17725904 TI - [Preventable deaths in hospitals]. PMID- 17725905 TI - [Cardiovascular risk factors in hemodialysis patients--reverse epidemiology]. AB - Cardiovascular Disease (CVD) is very common among hemodialysis (HD) patients. As the relation to the traditional risk factors is uncertain, strategies for preventing CVD in these patients cannot be uncritically extrapolated from the general population. In this review, data from epidemiological studies on HD patients are presented. We conclude that further research in the pathogenesis of CVD in HD patients is required for specific clinical interventional trials to be carried out and evidence based treatment strategies to be established. PMID- 17725906 TI - [Identification of new ovarian cancer biomarkers with proteomic analyses--the diagnostic tool of the future?]. AB - New non-invasive diagnostic tests for detection of ovarian cancer in early stages can improve survival. One approach is the proteomic analysis of serum or urine, which may be the technology needed. Preliminary proteomic analyses of serum and urine have shown a higher positive predictive value than that of the combination of serum CA125 and ultrasound examination, which actually is used preoperatively for the ovarian cancer diagnosis (RMI index). Identification of new ovarian cancer biomarkers will optimally be usable as an ovarian cancer-screening tool. PMID- 17725907 TI - [Pharmacotherapy for weight loss in patients with type 2 diabetes]. PMID- 17725908 TI - [Prevention of postoperative nausea and vomiting]. PMID- 17725909 TI - [Antidepressants in depression of the elderly]. PMID- 17725910 TI - [Skin suturing]. PMID- 17725911 TI - [Potentially preventable deaths in a medium sized community hospital]. AB - INTRODUCTION: The purpose of this study was to estimate the occurrence and causes of potentially preventable deaths at a medium sized community hospital. MATERIALS AND METHODS: A review of a consecutive series of records of 48 deceased patients (age 58-98 years, median 81 years, 40% males) was conducted by four observers, followed by a consensus conference in which the deaths were classified as potentially preventable according to a checklist, focusing on the occurrence of adverse events or failure to comply with evidence-based procedures. RESULTS: 10 of the 48 deaths were considered potentially preventable; in two cases the potential was considered significant, but the age and underlying diseases of the patients suggest that the potential number of saved life years is modest. The main reasons for preventability were unintended delays, ineffective treatment plans, and lack of reactions to new and important diagnostic information. CONCLUSION: The review of the deaths revealed a considerable number of potentially preventable cases. Furthermore, a number of suggestions for improvement were identified: (1) early identification and aggressive treatment of impending sepsis; (2) employment of routines to ensure that new diagnostic information is reviewed and acted upon and (3) systematic updating of competences in all staff members. PMID- 17725912 TI - [The cost of obesity on the Danish health care system]. AB - INTRODUCTION: The prevalence of obesity and obesity-related co-morbidities in the Danish adult population is continuously rising and demands on the Danish health care system are consequently increasing. Quantitative measures of the economic costs related to obesity constitute a necessary basis for the organization of treatments, health promotion and for health policies. MATERIALS AND METHODS: On the basis of studies of the prevalence of obesity in the Danish adult population and estimates of the increased risk of co-morbidity among obese, the number (and a sensitivity-interval) of hospital contacts in 2003 was calculated. Based on the results of these calculations and on treatment rates for the identified diagnosis groups, the costs related to the treatment of obesity and obesity-related co morbidities were estimated. RESULTS: In 2003 177,703 hospital contacts in Denmark were related to obesity. The costs related to these contacts summed up to euro 137.3 mill. (euro 88.8-174.0 mill.), corresponding to 2.8% (1.8-3.6%) of the running costs at Danish hospitals. CONCLUSION: The results of this analysis are equivalent to the results from similar analyses from other European countries with comparable health care systems. The health-economic costs related to obesity in Denmark depend on the prevalence of obesity and as a consequence are expected to rise as the current obesity epidemic further develops. PMID- 17725915 TI - [Uveitis--a manifestation of syphilis]. AB - We describe two cases of neurosyphilis whose diagnosis was based on ocular symptoms. Both patients were treated in the Eye Department for bilateral uveitis, and they were tested serologically positive for syphilis. The diagnoses of neurosyphilis were confirmed by demonstration of CSF pleocytosis and specific intrathecal antibody production. Both patients were treated with 21 million units of penicillin IV daily for 15 days. Ocular syphilis is an unusual manifestation of the disease but should be considered in patients with uveitis of uncertain origin, especially if the patient has a rash and/or headache. PMID- 17725913 TI - [Can Danish health care registries provide data for specific drug-related hospital admissions in type 2 diabetes?]. AB - INTRODUCTION: Preventable drug-related hospital admissions (pDRAs) occur frequently but with unknown incidence in type 2 diabetes. The objective of this study was to assess the extent to which Danish health care registries can provide data for specific pDRA indicators in diabetes. MATERIALS AND METHODS: Operationalization of indicators was based on a random 10% sample of the Danish population from 2001-2003 with data from The National Patient Registry, The National Health Insurance Service Registry and The Register of Medicinal Product Statistics. Persons with at least one prescription for an oral antidiabetic agent were identified as type 2 diabetes patients. The frequency and the DRG-value of pDRAs were identified for 2002-2003. RESULTS: The 22 defined indicators were operationalized. Indicator validity was reduced due to lack of laboratory data and data on actual medicine use. The patient material consisted of 9,791 persons and 15,645 person years. 1,198 persons were identified with 9,621 pDRAs. Renal problems preceded by no ACE-inhibitor or angiotensin-2-receptor antagonist therapy were frequent (63.85 (CI 59.89-67.81) per 1,000 person-years), as were secondary AMIs preceded by no ASA, beta-blocker or statin therapy (4.92 (CI 3.82 6.02), 9.52 (CI 7.99-11.05) and 12.66(CI 10.89-14.42) per 1,000 person years). The resulting costs of the identified pDRAs were estimated at DKK 55.7 mill. CONCLUSION: Danish health care registries can provide data for explicit pDRA indicators in diabetes. However, the validity is reduced as laboratory data and data on actual medicine use are not being registered. PMID- 17725916 TI - Allergen avoidance. Gallates. PMID- 17725918 TI - Genetics of nickel allergic contact dermatitis. AB - Nickel sulfate is the most frequently detected cause of allergic contact dermatitis in the world; the prevalence of nickel allergic contact dermatitis is between 8 and 11% in the general female population. Although it is well recognized that environmental factors are important in the pathogenesis of this dermatitis, some investigators have hypothesized that genetic factors are important as well. This review summarizes animal and human studies evaluating genetic factors in the development of allergic contact dermatitis from nickel. PMID- 17725920 TI - Prevalence of hand dermatitis in inpatient nurses at a United States hospital. AB - BACKGROUND: Hand dermatitis is a significant problem among inpatient nurses. Accurate population-based data on the prevalence and risk factors for hand dermatitis in this group are lacking. OBJECTIVE: To determine the prevalence of hand dermatitis in inpatient nurses at a US hospital. METHODS: Each nursing unit in a single hospital was visited twice by a single physician. All nurses working at the time of each visit were questioned and examined. No nurses were enrolled twice. RESULTS: Fifty-five percent (92 of 167) of the nurses had hand dermatitis. Among intensive care unit (ICU) nurses, the prevalence was 65% (35 of 54); among non-ICU nurses, the prevalence was 50% (57 of 113). In nurses with self-reported atopic dermatitis, the prevalence was 71% (12 of 17); in nurses without self reported atopic dermatitis, it was 53% (80 of 150). Data collection on variables such as hand hygiene and glove use relied on subject recall and was considered unreliable. There was a low prevalence of atopic patients. CONCLUSIONS: Hand dermatitis affects over 50% of inpatient nurses. Hand dermatitis appears to be more common in the ICU setting and in nurses with a self-reported history of atopy. PMID- 17725919 TI - Skin reactions to pimecrolimus cream 1% in patients allergic to propylene glycol: a double-blind randomized study. AB - BACKGROUND: The low concentration of propylene glycol (PG) in pimecrolimus cream makes it unlikely that the cream will induce a PG-related irritant or allergic contact dermatitis. OBJECTIVE: To assess reactions to pimecrolimus cream in patients who are allergic to PG. METHODS: A pilot double-blind within-patient study in 20 patients, with patch testing followed by a repeated open application test (ROAT). Limitations were that patch tests and ROATs were performed on normal skin, which may be less likely to develop an allergic response than would areas of active dermatitis. RESULTS: Positive PG patch-test results were confirmed in 16 patients. Patch-test scores were compatible with allergic reactions in only two patients. However, ROAT scores were negative for these two patients. Reactions with pimecrolimus or vehicle during ROAT were identified in three patients, but an allergic reaction was uncertain because none of these patients reacted with both pimecrolimus cream and vehicle. Reactions with pimecrolimus were significantly less frequent (p<.01) and less severe (p=.02) than with PG. CONCLUSION: In patients allergic to PG, pimecrolimus cream showed a very low potential to elicit allergic skin reactions. PMID- 17725921 TI - Hand dermatitis in auto mechanics and machinists. AB - BACKGROUND: Auto mechanics and machinists presenting with suspected allergic contact dermatitis (ACD) have traditionally been patch-tested with a standard screening tray and a specialty tray such as the Oil and Cooling Fluid Series. While this has proven useful for patch-testing the machinist, there is a need for the development of a more specific allergen testing tray for the auto mechanic. OBJECTIVE: The objective of the study was to compare clinical features and patch test results of auto mechanics and machinists with hand dermatitis to evaluate differences in allergen profiles. METHODS: We performed a chart review of 33 auto mechanics and 24 machinists referred to our Occupational Contact Dermatitis Clinic from 2002 to 2005 for evaluation of hand dermatitis. RESULTS: With a panel of 84 allergens, 52 positive reactions were detected in 17 cases of ACD in mechanics. The profiles were different from the cases of ACD diagnosed in 10 of 24 machinists. CONCLUSIONS: Mechanics and machinists differ in the spectrum of occupational exposures. Patch testing with greater numbers of allergens likely identifies a larger proportion of mechanics with occupationally relevant ACD. Further study is needed to determine the most appropriate allergens to include in a clinically useful "mechanic's tray." PMID- 17725922 TI - Cross-reactions between xanthates and rubber additives. AB - BACKGROUND: We previously described allergic contact dermatitis from xanthates used in the recovery of metals from mining ores. We observed cross-reactions with carbamates, believed to be due to the common "dithio" nucleus shared by both groups. OBJECTIVE: The present study was undertaken to establish the rate of cross-reactions between xanthates and rubber additives. METHODS: Between November 2002 and December 2005, 1,220 consecutive patients were patch-tested with sodium isopropyl xanthate 10% in petrolatum (pet) and with potassium amyl xanthate 10% pet and later 5% pet, in addition to the North American Contact Dermatitis Group standard series and other series as required by their conditions. RESULTS: Fifty one patients reacted to xanthates, carbamates, or thiurams; 26 reacted to xanthates only, and these reactions were felt to be irritant. Twenty-five patients reacted to xanthates and/or to one or more of the rubber additives, 12 had positive reactions to xanthates and to either carba mix or thiuram mix, 10 reacted to xanthates and carba mix, 9 reacted to xanthates and thiuram mix, and 8 showed positive reactions to xanthates and both mixes. However, 13 patients had positive reactions to carba mix and thiuram mix but did not react to xanthates. Six patients reacted to other rubber additives such as mercaptobenzothiazole, black rubber mix, and mixed dialkyl thioureas. Five of these patients also reacted to xanthates, 4 reacted to xanthates and carba mix, and 3 reacted to xanthates, carba mix, and thiuram mix. CONCLUSIONS: Of patients sensitized to carbamates, thiurams, or mercaptobenzothiazole, 50% exhibit cross-reactions with xanthates. Xanthates are irritants, and their patch-test concentrations should be lowered to 5% or less. PMID- 17725924 TI - Cyclosporin A treatment is associated with increased serum immunoglobulin E levels in a subgroup of atopic dermatitis patients. AB - Cyclosporin A is increasingly used in the treatment of severe refractory atopic dermatitis. Although cyclosporin A treatment is highly efficacious and relatively safe, we report four adult atopic dermatitis (AD) patients who deteriorated during long-term cyclosporin A treatment, with clinical signs and symptoms more severe than at the onset of treatment. Interestingly, these patients showed large increases of total serum immunoglobulin E (IgE) levels, paralleled by increasing disease severity and serum levels of thymus and activation-regulated chemokine. This implies that cyclosporin A may induce a shift to Th2, resulting in increased IgE synthesis, in a subpopulation of AD patients. We therefore suggest that in this subpopulation, treatment with anti-B cell or combined anti-B and T-cell treatment may be favorable. PMID- 17725923 TI - Sensitivity of petrolatum and aqueous vehicles for detecting allergy to imidazolidinylurea, diazolidinylurea, and DMDM hydantoin: a retrospective analysis from the North American Contact Dermatitis Group. AB - OBJECTIVE: To determine whether petrolatum or aqueous vehicles are more sensitive for detecting allergy to imidazolidinylurea (IU), diazolidinylurea (DU), and dimethylol dimethyl hydantoin (DM). The relationship of these allergens to formaldehyde sensitivity was also explored. METHODS: Retrospective analysis of patients patch-tested by the North American Contact Dermatitis Group. All patients were simultaneously tested to seven allergens (formaldehyde, IU in petrolatum [pet], IU aqueous [aq], DU pet, DU aq, DM pet, and DM aq). Data were analyzed in pairs with various "gold standard" definitions of "true allergy" and adjusting for correlated data. RESULTS: Reaction to at least one of the seven allergens occurred in 2,398 patients. In all cases except one (which just approached statistical significance), the petrolatum-based allergen was statistically significantly more sensitive than the same allergen in an aqueous base. Most of the patients allergic to the three preservatives were also allergic to formaldehyde, but most formaldehyde-allergic patients were not allergic to the IU, DU, or DM. CONCLUSION: Of these two vehicles, petrolatum is significantly more sensitive than an aqueous vehicle is for detecting allergy to IU, DU, and DM. PMID- 17725925 TI - Joint meeting of the Experimental Contact Dermatitis Research Group and the American Contact Dermatitis Society in Baltimore, MD, September 28 to 30, 2006. PMID- 17725926 TI - Epidermal growth factor receptor inhibitor-related folliculitis. PMID- 17725927 TI - Avoid the shriek with Shrek: video-distraction assist for pediatric patch testing. PMID- 17725928 TI - Dopamine D(1) and D(2) receptor agonism enhances antinociception mediated by the serotonin and noradrenaline reuptake inhibitor duloxetine in the rat formalin test. AB - Altered functioning of monoamine-containing pathways descending from supraspinal structures to the spinal dorsal horn contributes to injury-induced sensitization of nociceptive transmission. Antidepressant drugs as typified by the dual serotonin (5-HT) and noradrenaline reuptake inhibitor duloxetine attenuate various signs and symptoms of persistent pain in animals and humans. The current study assessed whether dopamine receptor agonists could further enhance the antinociceptive activity of duloxetine in an animal model of injury-induced central sensitization, the rat formalin test. Duloxetine (3-100 mg/kg, s.c.), the dopamine D(1) receptor agonist SKF-82958 (0.1-1 mg/kg, s.c.) and the dopamine D(2) receptor agonist quinpirole (0.003-0.1 mg/kg, s.c.) all significantly attenuated spontaneous nociceptive behaviours during the second phase of the test; duloxetine and quinpirole also attenuated nociceptive behaviours during first phase and interphase. These antinociceptive actions of SKF-82958 and quinpirole were selectively antagonized by SCH 23390 and eticlopride respectively. Remarkably, when completely inactive doses of duloxetine (3 mg/kg) and SKF-82958 (0.3 mg/kg) were combined, a marked attenuation of second phase nociceptive behaviours occurred (P<0.05 vs vehicle), indicative of analgesic synergy. Similarly, when an active antinociceptive dose of quinpirole (0.03 mg/kg, P<0.05 vs vehicle) was combined with an inactive dose of duloxetine (3 mg/kg), a potentiation of duloxetine-mediated antinociception was observed (P<0.001 vs vehicle). Taken together, these results suggest that antidepressant drugs that can enhance the activity of 5-HT, noradrenaline and dopamine neurotransmission within nociceptive pathways should provide a broader spectrum of antinociception than dual mechanism of action reuptake inhibitors in animal models of injury-induced persistent nociception. PMID- 17725929 TI - Influence of Hypericum perforatum extract and its single compounds on amyloid beta mediated toxicity in microglial cells. AB - As immunocompetent cells of the brain, microglia are able to counteract the damaging effects of amyloid-beta in Alzheimer's disease by phagocytosis-mediated clearance of protein aggregates. The survival and health of microglia are therefore critical for attenuating and preventing neurodegenerative diseases. In a microglial cell line pretreated with St. John's wort (Hypericum perforatum L.) extract (HPE), the cell death evoked by treatment with amyloid-beta (25-35) and (1-40) was attenuated significantly in a dose-dependent manner. Investigation of the single compounds in the extract revealed that the flavanols (+)-catechin and (-)-epicatechin increase cell viability slightly, whereas the flavonol quercetin and its glycosides rutin, hyperosid and quercitrin showed no effect on cell viability. In contrast, at the same concentration, the flavonoids reduced the formation of amyloid-induced reactive oxygen species in microglia, indicating that improvement of cell viability by the catechins is not correlated to the antioxidant activity. No influence of HPE on the capacity of microglia to phagocytose sub-toxic concentrations of fibrillar amyloid-beta (1-40) was observed. Other experiments showed that HPE, (+)-catechin and (-)-epicatechin can alter cellular membrane fluidity and thereby may have a beneficial effect on cell health. Our findings provide in vitro evidence that treatment especially with the complex plant extract HPE may restore or improve microglial viability and thereby attenuate amyloid-beta mediated toxicity in Alzheimer's disease. PMID- 17725930 TI - Cross-national difference in the prevalence of depression caused by the diagnostic threshold. AB - BACKGROUND: According to published reports, the prevalence rates of major depressive disorder (MDD) in East-Asian countries are lower than in the West, but the reasons for this difference have not been fully investigated. METHODS: This study compared the Korean Epidemiologic Catchment Area study (KECAS) sample with the National Comorbidity Survey (NCS, USA) sample. In total, this study included 5349 participants in KECAS and 7423 in NCS aged 18-54 years. The Composite International Diagnostic Interview (CIDI) assessed for MDD. Analysis of the individual symptoms of MDD was completed. RESULTS: Diagnostic threshold of MDD was higher in KECAS participants than in NCS participants. Koreans diagnosed with MDD showed more work impairment than Americans with MDD. Koreans were more likely to express the symptoms like "low energy" and "concentration difficulty," but less to the symptoms like "depressed mood" and "thoughts of death" during an episode of MDD. LIMITATIONS: The Diagnostic and Statistical Manual of Mental Disorders (DSM) framework was the basis for the majority of the comparisons made in this study. Various depressive symptoms not included in the DSM framework were unlikely to be detected. CONCLUSIONS: Cross-cultural differences in rates of MDD are attributable to diagnostic thresholds. Symptom patterns and forms of depression in Korea, as defined by the DSM framework, are not identical to those in the U.S. PMID- 17725931 TI - Smoking-related videos for use in cue-induced craving paradigms. AB - Environmental cues (e.g., the sight of a cigarette) have long been recognized as important triggers for craving in smokers. Available imaging technologies (e.g., fMRI) allow investigation of the neural mechanisms for cue-induced craving, but there stands a need for a cue-delivery system compatible with an MRI environment. We developed a standardized set of 24 high-resolution videos, 12 containing cigarette smoking scenes (e.g., lighting up), and 12 containing neutral scenes (e.g., reading a book), each 30 s long, with comparable lighting, visual complexity, and background filmed by a professional cinematographer. Study participants were 20 smokers (mean age=37.7 years, 50% female). Each was exposed to the 24 videos in a random order under laboratory conditions. Dependent measures included heart rate, blood pressure, skin conductance, skin temperature, and self-reported craving (0-100) following each video. Overall findings indicated that smokers had greater reactivity to the smoking videos than to neutral videos (p<.01). Follow-up univariate analyses revealed significant cue effects on self-reported craving, galvanic skin response, and skin temperature. Interestingly, exploratory examination of gender revealed that men had higher blood pressure and skin temperature responses than women, and that women had higher responses when viewing videos of women smoking than when viewing men smoking. Results support this set of videos as an effective tool for investigation of cue-elicited craving, and raise the possibility of unique gender effects in cue reactivity. PMID- 17725932 TI - Predicting the initiation of substance abuse in Iranian adolescents. AB - Limited information is available on adolescent's substance abuse in Iran. The aims of this study are to estimate incidence rate of substance abuse among the sample of 10-grade male students in Tabriz City (northwestern region of Iran), and to evaluate the associated factors. Of all grade-10 male students in Tabriz, 1785 (13.7%) were randomly sampled, and were assessed twice. A self-administered questionnaire with 48 questions was distributed to students in February and March 2005. After one year (February and March 2006), another questionnaire with 10 items was distributed to those students to determine the incidence rate of substance abuse. The influence of different factors on substance abuse was evaluated with a logistic regression model. The mean age of the subjects was 16.3+/-0.87 (min. 15, max. 19) years. At the end of follow-up, 10.1% and 2.2% of students reported incidence of alcohol use and drug abuse respectively. This study has shown low prevalence of substance abuse, but higher incidence rate of substance abuse. PMID- 17725933 TI - Propofol sedation during endoscopic procedures: how much staff and monitoring are necessary? AB - BACKGROUND: Propofol has been shown to be safe for nonanesthetist use during GI endoscopy. However, published studies involved propofol administration by an additional nurse or used specialized patient monitoring or were carried out in tertiary hospitals. OBJECTIVE: Considering the downward pressure on reimbursement for endoscopic procedures, we asked how much staff and monitoring is necessary for safe use of propofol. SETTING: Two private gastroenterology practices. PATIENTS AND DESIGN: A total of 27,061 endoscopic procedures (14,856 EGDs and 12,205 colonoscopies) were prospectively assessed regarding patient characteristics, American Society of Anesthesiologists (ASA) status, dosage of propofol, fall of oxygen saturation below 90%, need to increase nasal oxygen administration above 2 L/min, and need for assisted ventilation. INTERVENTION: Propofol was administered by the endoscopy nurse supervised by the endoscopist. Patient monitoring consisted of only pulse oximetry and clinical assessment. RESULTS: The mean propofol dose for EGD was 161 mg (range 50-650 mg). During colonoscopy patients received a mean propofol dose of 116 mg (30-500 mg) in addition to 25 mg of meperidine. Oxygen saturation fell below 90% (lowest 74%) in 623 procedures (2.3%), normalizing within less than 30 seconds by stimulating the patient and increasing the nasal oxygen flow to 4 to 10 L/min. Six patients (ASA III) required mask ventilation for less than 30 seconds. No endotracheal intubation was necessary. LIMITATIONS: There was no further follow-up regarding adverse events after patient discharge from the endoscopy unit. CONCLUSIONS: An endoscopy team, consisting of 1 physician endoscopist and 1 endoscopy nurse, can safely administer propofol sedation for GI endoscopy in a practice setting without additional staff or specialized monitoring. PMID- 17725934 TI - Premedication with orally administered lorazepam in adults undergoing ERCP: a randomized double-blind study. AB - BACKGROUND: Restlessness often complicates ERCP and may be a reason for premature termination of the procedure. OBJECTIVE: Our purpose was to evaluate whether a premedication with orally administered lorazepam could reduce the need for sedatives and improve sedation quality. DESIGN: Randomized double-blind trial. SETTING: Therapeutic ERCP with an intravenous sedation containing midazolam, propofol, and S(+)-ketamine. PATIENTS: 95 inpatients (aged 20-91 years). INTERVENTIONS: 1 mg of lorazepam (n=47) or placebo (n=48) given orally before ERCP. MAIN OUTCOME MEASUREMENT: Total amount of administered propofol. RESULTS: Heart rate, blood pressure, number of oxygen desaturations, and states of restlessness did not differ between the groups. The same amount of midazolam was administered in both groups. There was no significant difference in the total amount of propofol to achieve adequate sedation (lorazepam vs placebo: 71+/-5 vs 63+/-4 microg/kg/min, mean+/-SE). Paradoxically, patients pretreated with lorazepam even needed more propofol in the early phase of sedation (275+/-39 vs 159+/-37 microg/kg in minutes 5-10, P<.05) and the total amount of ketamine administered was higher in this group as well (15.8+/-1.4 vs 11.3+/-1.2 microg/kg/min, P<.05). In both groups there were high rates of satisfaction with the course of the procedure evaluated both by the endoscopists and the patients. CONCLUSION: The trial failed to show an advantage of an oral premedication with lorazepam. The amount of sedatives administered in the lorazepam group even tended to be higher. A premedication with lorazepam may be counterproductive when followed by sedation containing another benzodiazepine. PMID- 17725935 TI - Big NAPS, little NAPS, mixed NAPS, computerized NAPS: what is your flavor of propofol? PMID- 17725936 TI - Endoscopic therapy for high-grade dysplasia in Barrett's esophagus: ablate, resect, or both? PMID- 17725937 TI - Staging of esophageal cancer by EUS: staging accuracy revisited. AB - BACKGROUND: EUS plays an important role in the preoperative staging of esophageal cancer. Recent data have called into question the staging accuracy of EUS, particularly in patients with early disease. OBJECTIVE: Our goals were to assess our institution's EUS staging accuracy by experienced endosonographers in a contemporary cohort of patients encompassing a wide range of disease stages and to assess staging accuracy after dilation of malignant strictures. DESIGN: Retrospective data review. SETTING: Single tertiary care center. PATIENTS AND INTERVENTIONS: A total of 42 patients with esophageal cancer undergoing preoperative EUS staging without neoadjuvant chemoradiotherapy between December 1999 and December 2004 were evaluated. MAIN OUTCOME MEASUREMENTS: EUS T and N stage sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. RESULTS: EUS accurately predicted T stage in 76% of cases and N stage in 89% of cases. Staging accuracy for T3 versus T1 and T2 disease and for N0 versus N1 disease was not significantly different. In 11 cases, malignant strictures required dilation, with 6 tumors being passable post dilation. Post dilation, T staging accuracy was 80% in impassable tumors and 100% in passable tumors, and N staging accuracy was 100% in the passable tumors. LIMITATIONS: Relatively small number of patients. CONCLUSIONS: EUS accurately predicts T and N stage in patients with a range of disease stages. EUS provides good staging accuracy after dilation of malignant strictures regardless of whether full tumor traversal post dilation is possible. PMID- 17725939 TI - EUS and chronic pancreatitis: seeing is believing? PMID- 17725938 TI - Preliminary experience comparing routine cytology results with the composite results of digital image analysis and fluorescence in situ hybridization in patients undergoing EUS-guided FNA. AB - BACKGROUND: Studies indicate enhanced diagnostic accuracy for digital image analysis (DIA) and fluorescence in situ hybridization (FISH) versus routine cytology examination (RC) when biliary strictures are evaluated. These tumor markers have not been applied to EUS-guided FNA. OBJECTIVE: Our purpose was to determine the accuracy of RC versus the composite results of DIA/FISH. DESIGN: Patients enrolled with known or suspected malignancy. The final diagnosis was based on strict cytopathologic and imaging criteria and 12-month follow-up. SETTINGS: Tertiary referral center. PATIENTS: A total of 39 patients were enrolled in whom each diagnostic test was performed on samples from 42 sites to evaluate lymphadenopathy (n=19), pancreatic mass (n=19), esophageal or gastric wall mass (n=3), and thyroid mass (n=1). INTERVENTIONS: EUS-guided FNA with RC, DIA, and FISH. MAIN OUTCOME MEASUREMENT: Diagnostic accuracy of RC, DIA, and FISH. RESULTS: Malignancy was diagnosed in 30 of 42 patients, including esophageal squamous cell carcinoma, esophageal adenocarcinoma, gastric adenocarcinoma, pancreatic adenocarcinoma, pancreatic mucinous cystic neoplasia, intraductal papillary mucinous neoplasia, metastatic forearm sarcoma, small cell and non-small cell lung cancer, thyroid carcinoma, malignant GI stromal tumor, melanoma, adenocarcinoma of unknown primary, and lymphoma. The sensitivity, specificity, and accuracy of DIA/FISH versus RC for detecting malignancy were 97%, 100%, and 98% versus 87%, 100%, and 90%, respectively. LIMITATIONS: Single center pilot study. CONCLUSIONS: Our findings suggest that DIA and FISH processing of EUS-guided FNA specimens provides higher diagnostic accuracy than RC does. These data suggest that these tumor markers incorporate generic targets as suggested by the high diagnostic sensitivity in this patient cohort with diverse pathologic conditions. PMID- 17725940 TI - A randomized controlled trial of pentoxifylline for the prevention of post-ERCP pancreatitis. AB - BACKGROUND: Pentoxifylline can ameliorate pancreatitis in animal models because of its anti-tumor necrosis factor properties. OBJECTIVE: Our purpose was to study the safety and efficacy of pentoxifylline in the prevention of post-ERCP pancreatitis. DESIGN: Patients due to undergo ERCP for various indications were randomized to receive pentoxifylline 400 mg orally 3 times, beginning the day before ERCP (2 and 10 pm) until the night after the procedure (6 am and 2 and 10 pm) or to receive no preventive medication. Serum amylase values were determined before and 6 and 24 hours after ERCP. Diagnosis and grading of the severity of complications was performed according to consensus criteria. PATIENTS: One hundred fifty-eight patients received pentoxifylline (group A) and 162 had no medication (group B). The groups were similar in distributions of sex, biliary sphincterotomy, pancreatography, pancreatic duct cannulations, stone extraction, stent placement, and presence of periampullary diverticulum. Group A patients were younger (mean age 63 vs 68 years, P<.05) and biliary colic was a more frequent indication (30 vs 12, P<.05). RESULTS: Nine (5.6%) patients in group A and 5 (3%) in group B had pancreatitis (2 and 1 severe, respectively; P=.28). Serum amylase values were similar in baseline and 6- and 24-hour samples. Two (1.2%) patients in group A and 7 (4.3%) in group B had hemorrhage. LIMITATIONS: This was not a double-blind trial. CONCLUSIONS: In this study pentoxifylline did not protect against post-ERCP pancreatitis or hyperamylasemia. PMID- 17725941 TI - Recognition and appropriate management of dysplasia-associated lesions or masses in inflammatory bowel disease--experience does matter. PMID- 17725942 TI - Evaluation of postsurgical recurrence in Crohn's disease: a new indication for capsule endoscopy? AB - BACKGROUND: Recurrence after surgery to treat Crohn's disease is frequent and unpredictable. The efficacy of postsurgery capsule endoscopy in detecting recurrence in patients with Crohn's disease is yet to be confirmed. OBJECTIVE: To assess the safety, accuracy, and therapeutic impact of capsule endoscopy in these patients. DESIGN: Crohn's disease recurrence at the neoileum (Rutgeers score) was assessed in the patients by colonoscopy and capsule endoscopy. The M2A Patency Capsule (Given Imaging, Yoqneam, Israel) was administered 1 week before capsule endoscopy. Capsule endoscopy was performed within 2 weeks of colonoscopy. Investigators were blinded to the results of each technique. Patient comfort during the procedures was recorded. PATIENTS: Twenty-four patients with Crohn's disease with ileocolonic anastomosis were prospectively included. All patients were asymptomatic and did not receive any prophylactic treatment. MAIN OUTCOME MEASUREMENTS: Neoileum recurrence. RESULTS: A colonoscopy was performed in all patients, although the neoileum could not be reached in 3 of them. M2A Patency Capsule excretion was delayed in 2 patients; thus capsule endoscopy was given only to 22 patients. Recurrence was visualized with colonoscopy in 6 patients and with capsule endoscopy in 5. Ten additional recurrences were visualized only with capsule endoscopy. Moreover, proximal involvement was detected in 13 patients. Therapeutic management was modified in 16 patients. All patients preferred capsule endoscopy. CONCLUSIONS: Capsule endoscopy is more effective in the evaluation of recurrence after surgery for Crohn's disease and is better tolerated than colonoscopy. This is of significant therapeutic relevance. PMID- 17725943 TI - Postoperative endoscopic surveillance in Crohn's disease: bottom up or top down? PMID- 17725944 TI - Survival of elderly persons undergoing colonoscopy: implications for colorectal cancer screening and surveillance. AB - BACKGROUND: In the elderly, the increased prevalence of colorectal neoplasia and the protective effect of colonoscopy may be offset by advancing age and comorbidity. OBJECTIVE: To describe and quantify the endoscopic findings, survival, and predictors of mortality of elderly persons after colonoscopy. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study of persons aged>or=75 years who underwent colonoscopy in 1999 and 2000 at a U.S. Veterans Affairs facility and urban county hospital. MAIN OUTCOME MEASURES: Advanced neoplasms were defined as colorectal cancer (CRC), polyp with high-grade dysplasia, villous histologic features, or tubular adenoma>or=1 cm. Comorbidity was measured with the Charlson comorbidity index. Subjects were followed until death or study closure. RESULTS: Of 469 eligible subjects, 65 were excluded and 404 were included in the study. Fifty-nine of 404 (15%) had an advanced neoplasm, including 8 (2%) with CRC. There were 167 deaths (41%); the mean overall survival was 4.1+/-0.1 years (median 5.95 years). A symptomatic indication for colonoscopy was not predictive of death. Mortality was predicted by age (hazard ratio 1.16 for each year increase beyond age 75 years, 95% CI 1.07-1.3, P=.0003) and Charlson score (hazard ratio 8.3 for each point increase, 95% CI 1.4-48.5, P=.02). The median survival of patients aged 75 to 79 years was >5 years if the Charlson score was or=80 years, the median survival was <5 years regardless of Charlson score. LIMITATIONS: Retrospective design. CONCLUSIONS: In this cohort of elders, age and comorbidity were predictors of death. The protective effect of younger age lessens as comorbidity increases. These findings may have important implications for CRC screening and surveillance in elders. PMID- 17725945 TI - Potential and present limitation of endocytoscopy in the diagnosis of esophageal squamous-cell carcinoma: a multicenter ex vivo pilot study. AB - BACKGROUND: Endocytoscopy enables the in vivo observation of cellular nuclei in the GI tract. However, potential and present limitations of endocytoscopy have not been elucidated in detail. OBJECTIVE: To investigate whether endocytoscopic images of cancerous and normal squamous cells in the esophagus correspond with horizontal histology of the mucosal surface. DESIGN: An ex vivo pilot study. SETTING: Multiple academic institutions. MATERIALS: Endoscopically or surgically resected human esophagus obtained between May 2006 and July 2006. INTERVENTIONS: Endocytoscopic observation was performed on small areas of cancerous lesions and corresponding normal squamous cells. Biopsy specimens were then retrieved from the areas scanned to make horizontal histologic sections. MAIN OUTCOME MEASUREMENTS: Comparison of the images obtained by endocytoscopy and histology and comparison of the mean numbers of the total nuclei per endocytoscopic image obtained in cancerous and normal areas. RESULTS: Twenty-seven esophageal squamous cell carcinomas were acquired and evaluable pairs of an endocytoscopic image and a histological picture were obtained at 12 cancerous and 14 normal areas that showed similar morphologies between them. The mean (+/-SD) numbers of the total nuclei per image were 129+/-14.8 at the normal area and 550+/-66.5 at the cancerous area, respectively, which were significantly different between groups (P<.0001). LIMITATIONS: Only a comparison of cancerous and normal squamous cells in the esophagus at the ex vivo setting. CONCLUSIONS: Although endocytoscopic images closely correlated with conventional histology in the esophagus, appropriate preconditioning to constantly obtain sufficient image quality and universal criteria for endocytoscopic diagnosis of various diseases are essential before clinical application. PMID- 17725947 TI - Enhancing the quality of colonoscopy: the importance of bowel purgatives. PMID- 17725948 TI - Small-caliber endobronchial ultrasonic videoscope: successful transesophageal and transgastric FNA after failed passage of a standard ultrasonic endoscope. AB - BACKGROUND: EUS-guided tissue acquisition is a valuable technique. Obstructing lesions of the oropharynx or esophagus may preclude passage of a standard echoendoscope. In the past this has prevented EUS-guided tissue sampling. The recently introduced small-caliber ultrasonic bronchovideoscope (developed for endobronchial ultrasound) may allow EUS-guided FNA in this setting. OBJECTIVE: Our purpose was to assess the possible use of the ultrasonic bronchovideoscope to perform upper GI EUS in patients where passage of standard EUS scope was unsuccessful. DESIGN: A descriptive case series. SETTING: A tertiary referral center. RESULTS: Two patients were evaluated after failure of passage of a standard echoendoscope (1 with congenital narrowing of the esophageal inlet, 1 with postoperative deformity). In both cases, sonographic visualization of the lesion of concern was achieved and FNA was performed successfully. CONCLUSIONS: The ultrasonic bronchovideoscope may be a valuable tool to perform FNA of mediastinal and GI lesions in situations when a standard ultrasonic endoscope cannot be passed because of luminal narrowing. PMID- 17725949 TI - Endoscopic evaluation of the defunctionalized stomach by using ShapeLock technology (with video). AB - BACKGROUND: Patients with Roux-en-Y gastric bypass (RYGB) present a unique problem if they require diagnostic or therapeutic interventions for which the pancreatobiliary limb or the defunctionalized stomach must be accessed. Novel shape-locking guides have been reported in the literature to reduce looping during colonoscopy, and a new guide is now available to assist with enteroscopy. OBJECTIVE: To use ShapeLock technology to permit evaluation of the defunctionalized stomach. DESIGN: Observational case series. SETTING: Tertiary care center. PATIENTS: Nine patients with a history of RYGB referred for repeat endoscopic evaluation after initial enteroscopy failed to reach the excluded stomach. INTERVENTIONS: After achieving appropriate levels of sedation, a standard enteroscope was back-loaded with the ShapeLock enteroscopy guide and was inserted through the mouth. The device was moved through the gastrojejunal (GJ) anastomosis, along the Roux limb, and into the distal pancreatobiliary limb. The device was then locked, which allowed the enteroscope to be advanced to the defunctionalized stomach. RESULTS: The ShapeLock guide was able to be advanced to the excluded stomach and perform a thorough examination of the pancreatobiliary limb in 8 of 9 patients, without complications. In 1 patient, the diameter of the GJ anastomosis prevented passage of the device. CONCLUSIONS: The ShapeLock enteroscopy guide can allow access to the upper-GI tract in patients after RYGB, provided the GJ anastomosis is of adequate diameter. This study suggested that the technique is safe and has the potential to allow therapeutic interventions in the defunctionalized stomach and duodenum, including ERCP. PMID- 17725950 TI - EUS-guided cholecystenterostomy: a new technique (with videos). AB - BACKGROUND: The cornerstone of management for acute cholecystitis is cholecystectomy. However, surgical intervention is contraindicated in the occasional patient. EUS-guided transduodenal gallbladder drainage may represent an effective minimally invasive alternative. OBJECTIVES: To describe a new technique, EUS-guided cholecystenterostomy. DESIGN AND SETTING: A single-center retrospective case series. PATIENTS: Three patients with severe acute cholecystitis unresponsive to conservative management who were deemed unfit for cholecystectomy. INTERVENTIONS: Under combined EUS and fluoroscopic guidance, cholecystenterostomy was performed via needle puncture, guidewire insertion, cystoenterostome passage, and stent placement. MAIN OUTCOME MEASURES: Technical success, clinical progress, immediate and long-term complications, and recurrence of cholecystitis. LIMITATIONS: Pilot series. RESULTS: Cholecystenterostomy was performed successfully in all patients. Rapid improvement in clinical status and inflammatory parameters ensued. A minor intraprocedural bile leak occurred in 1 patient, without significant clinical sequelae. Cholecystitis did not recur in any patient. CONCLUSIONS: EUS-guided cholecystenteric drainage is technically feasible and appears to be a safe and effective procedure. Via this technique, gallbladder drainage and resolution of related sepsis may be achieved in patients with acute cholecystitis who are unfit for surgery. PMID- 17725951 TI - EUS-guided angiography: a novel approach to diagnostic and therapeutic interventions in the vascular system. AB - BACKGROUND: Indications for diagnostic and therapeutic procedures under EUS guidance continue to expand. OBJECTIVE: To assess the feasibility and safety of EUS-guided angiography in a live porcine model. SETTING: Five acute experiments under general anesthesia. DESIGN AND INTERVENTIONS: A linear echoendoscope was advanced into the stomach. Thoracic and abdominal aorta, celiac axis, superior mesenteric and splenic artery, splenic, portal, and hepatic veins were injected with contrast by using FNA needles under fluoroscopy. The animals were then killed for postmortem examination. MAIN OUTCOME MEASUREMENTS: Ability to achieve angiography without complications. RESULTS: All vessels were identified and punctured without technical difficulties. Injections of the large-caliber vessels resulted in a blush of contrast, whereas selective injection of the smaller vessels (splenic artery, hepatic veins) demonstrated clear vascular opacification. Injection of contrast was technically easiest with the 19-gauge FNA needle and most difficult with the 25-gauge needle. There were no changes in vital signs and hemodynamic parameters during vascular injection of any vessel. At necropsy, the 25-gauge FNA needle did not cause any visible vascular injury or bleeding. The 22-gauge needle left a visible puncture mark without active bleeding. In 1 of 5 pigs, the 19-gauge needle caused a localized vascular hematoma around large-caliber vessels and 150 mL of intra-abdominal blood. LIMITATION: Technical challenges remain to achieve an adequate flow rate of contrast for prolonged visualization of large vessels. CONCLUSION: EUS-guided angiography is technically easy and safe and has potential for a wide array of diagnostic and therapeutic vascular interventions. PMID- 17725952 TI - EUS-guided angiography: a future indication for EUS? PMID- 17725953 TI - Gallstone ileus presenting with hematemesis. PMID- 17725954 TI - Radiation enteritis diagnosed by capsule endoscopy. PMID- 17725955 TI - "Watermelon rectum" associated with multiple vascular ectasia in the colon. PMID- 17725956 TI - Endoscopic clips for closing esophageal perforations: case report and pooled analysis. AB - BACKGROUND: Acute and chronic esophageal perforations have traditionally been treated with surgery or a conservative approach. Recently, endoscopic repair has been reported in some case reports. OBJECTIVE: To describe a case of a chronic esophagoperitoneal fistula successfully closed by endoscopic clips after several failed reoperations and stent placement. To perform a pooled analysis of the reports describing such closures. DESIGN: Case report and pooled analysis. SETTING: Tertiary-care hospitals. PATIENTS: Our patient presented with mature perforation in the distal esophagus caused by laparoscopic band gastroplasty. Patients for pooled analysis identified by a MEDLINE search (1966 to January 2007) performed for all the English language articles that reported esophageal perforation/fistulae and endoscopic clips. INTERVENTIONS: Endoscopic clip application after ablation of epithelialized edges in our patient. Pooled analyses for demographic and perforation variables, along with predictors for closure time after clipping, were performed. MAIN OUTCOME MEASUREMENTS: Closure of esophageal perforations. RESULTS: The fistula in our patient closed in 3 weeks after endoscopic clipping. The literature review identified a total of 11 articles that describe 17 patients (acute 7, intermediate 4, and chronic 6). The most common cause was iatrogenic (65%), and the size of the perforation ranged from 3 to 25 mm. The median healing time after clipping was 18 days (interquartile range 6-26). Both univariable and multivariable analyses identified only the duration of perforation as a significant predictor of closure time, P values .003 and .02, respectively. LIMITATIONS: Small sample size, nonrandomized sample. CONCLUSIONS: Endoclips may be effective for closing both acute and chronic esophageal perforations. The duration of the perforation is a significant factor for predicting closure time. PMID- 17725957 TI - Cap-assisted ERCP in patients with a Billroth II gastrectomy. AB - BACKGROUND: ERCP is difficult in patients with a Billroth II gastrectomy because of anatomical changes. OBJECTIVE: Cap-assisted ERCP can improve the cannulation rate and the success rate of stone removal. DESIGN: Case series. SETTING: A tertiary referral center. PATIENTS AND INTERVENTIONS: Ten consecutive patients with bile-duct stones (9) or a distal common bile duct stricture (1), who had previously undergone Billroth II gastrectomy and were referred for ERCP, were analyzed for the outcome of their ERCP. All procedures were carried out with a cap-fitted regular forward-viewing endoscope. MAIN OUTCOME MEASUREMENTS: Ability to perform afferent loop intubation and bile-duct cannulation. RESULTS: Of 10 patients in whom ERCP was attempted, afferent loop intubation and selective bile duct cannulation were achieved in all patients (100%). Endoscopic sphincterotomy (EST) was successful in all 10 patients (100%). All stones were removed by EST alone in 7 patients and by both EST and endoscopic papillary balloon dilation in 2 patients. There were no serious complications in the patients. LIMITATIONS: Small sample size, single-center experience. CONCLUSIONS: Diagnostic and therapeutic ERCP with a cap-fitted regular forward-viewing endoscope was successful in all patients with a prior Billroth II gastrectomy. The high rate of successful ERCP was achieved by improving afferent loop intubation and bile-duct cannulation with a cap-fitted endoscope. PMID- 17725958 TI - Polyflex esophageal stent migration with elimination per rectum. PMID- 17725959 TI - Hands-off conversion from an orobiliary to a nasobiliary tube: the straightforward way. PMID- 17725961 TI - Is there any need for video capsule endoscopy evaluation in postduodenal small bowel polyps detection in familial adenomatous polyposis? PMID- 17725962 TI - Persistence of resolution clips on colorectal polypectomy sites. PMID- 17725963 TI - Endoloop-assisted amputation of a large rectal lipoma. PMID- 17725964 TI - Mechanisms of gradient detection: a comparison of axon pathfinding with eukaryotic cell migration. AB - The detection of gradients of chemotactic cues is a common task for migrating cells and outgrowing axons. Eukaryotic gradient detection employs a spatial mechanism, meaning that the external gradient has to be translated into an intracellular signaling gradient, which affects cell polarization and directional movement. The sensitivity of gradient detection is governed by signal amplification and adaptation mechanisms. Comparison of the major signal transduction pathways underlying gradient detection in three exemplary chemotaxing cell types, Dictyostelium, neutrophils, and fibroblasts and in neuronal growth cones, reveals conserved mechanisms such as localized PI3 kinase/PIP3 signaling and a common output, the regulation of the cytoskeleton by Rho GTPases. Local protein translation plays a role in directional movement of both fibroblasts and neuronal growth cones. Ca(2+) signaling is prominently involved in growth cone gradient detection. The diversity of signaling between different cell types and its functional implications make sense in the biological context. PMID- 17725965 TI - Leptin and the regulation of the hypothalamic-pituitary-adrenal axis. AB - Leptin, the product of the obesity gene (ob) predominantly secreted from adipocytes, plays a major role in the negative control of feeding and acts via a specific receptor (Ob-R), six isoforms of which are known at present. Evidence has been accumulated that leptin, like other peptides involved in the central regulation of food intake, controls the function of the hypothalamic-pituitary adrenal (HPA) axis, acting on both its central and peripheral branches. Leptin, along with Ob-R, is expressed in the hypothalamus and pituitary gland, where it modulates corticotropin-releasing hormone and ACTH secretion, probably acting in an autocrine-paracrine manner. Only Ob-R is expressed in the adrenal gland, thereby making it likely that leptin affects it by acting as a circulating hormone. Although in vitro and in vivo findings could suggest a glucocorticoid secretagogue action in the rat, the bulk of evidence indicates that leptin inhibits steroid-hormone secretion from the adrenal cortex. In keeping with this, leptin was found to dampen the HPA axis response to many kinds of stress. In contrast, leptin enhances catecolamine release from the adrenal medulla. This observation suggests that leptin activates the sympathoadrenal axis and does not appear to agree with its above-mentioned antistress action. Leptin and/or Ob-R are also expressed in pituitary and adrenal tumors, but little is known about the role of this cytokine in the pathophysiology. PMID- 17725966 TI - Focal adhesion kinase and p53 signaling in cancer cells. AB - The progression of human cancer is characterized by a process of tumor cell motility, invasion, and metastasis to distant sites, requiring the cancer cells to be able to survive the apoptotic pressures of anchorage-independent conditions. One of the critical tyrosine kinases linked to these processes of tumor invasion and survival is the focal adhesion kinase (FAK). FAK was first isolated from human tumors, and FAK mRNA was found to be upregulated in invasive and metastatic human breast and colon cancer samples. Recently, the FAK promoter was cloned, and it has been found to contain p53-binding sites. p53 inhibits FAK transcription, and recent data show direct binding of FAK and p53 proteins in vitro and in vivo. The structure of FAK and p53, proteins interacting with FAK, and the role of FAK in tumorigenesis and FAK-p53-related therapy are reviewed. This review focuses on FAK signal transduction pathways, particularly on FAK and p53 signaling, revealing a new paradigm in cell biology, linking signaling from the extracellular matrix to the nucleus. PMID- 17725967 TI - Cell and molecular biology of the spindle matrix. AB - The concept of a spindle matrix has long been proposed to account for incompletely understood features of microtubule spindle dynamics and force production during mitosis. In its simplest formulation, the spindle matrix is hypothesized to provide a stationary or elastic molecular matrix that can provide a substrate for motor molecules to interact with during microtubule sliding and which can stabilize the spindle during force production. Although this is an attractive concept with the potential to greatly simplify current models of microtubule spindle behavior, definitive evidence for the molecular nature of a spindle matrix or for its direct role in microtubule spindle function has been lagging. However, as reviewed here multiple studies spanning the evolutionary spectrum from lower eukaryotes to vertebrates have provided new and intriguing evidence that a spindle matrix may be a general feature of mitosis. PMID- 17725968 TI - Mitochondrial biology and disease in Dictyostelium. AB - The cellular slime mold Dictyostelium discoideum has become an increasingly useful model for the study of mitochondrial biology and disease. Dictyostelium is an amoebazoan, a sister clade to the animal and fungal lineages. The mitochondrial biology of Dictyostelium exhibits some features which are unique, others which are common to all eukaryotes, and still others that are otherwise found only in the plant or the animal lineages. The AT-rich mitochondrial genome of Dictyostelium is larger than its mammalian counterpart and contains 56kb (compared to 17kb in mammals) encoding tRNAs, rRNAs, and 33 polypeptides (compared to 13 in mammals). It produces a single primary transcript that is cotranscriptionally processed into multiple monocistronic, dicistronic, and tricistronic mRNAs, tRNAs, and rRNAs. The mitochondrial fission mechanism employed by Dictyostelium involves both the extramitochondrial dynamin-based system used by plant, animal, and fungal mitochondria and the ancient FtsZ-based intramitochondrial fission process inherited from the bacterial ancestor. The mitochondrial protein-import apparatus is homologous to that of other eukaryote, and mitochondria in Dictyostelium play an important role in the programmed cell death pathways. Mitochondrial disease in Dictyostelium has been created both by targeted gene disruptions and by antisense RNA and RNAi inhibition of expression of essential nucleus-encoded mitochondrial proteins. This has revealed a regular pattern of aberrant mitochondrial disease phenotypes caused not by ATP insufficiency per se, but by chronic activation of the universal eukaryotic energy-sensing protein kinase AMPK. This novel insight into the cytopathological mechanisms of mitochondrial dysfunction suggests new possibilities for therapeutic intervention in mitochondrial and neurodegenerative diseases. PMID- 17725969 TI - Oxytocin and the human prostate in health and disease. AB - Oxytocin is a peptide hormone produced by the neurohypophysis. The discovery that the peptide is produced locally within the male and female reproductive tracts has raised the possibility that oxytocin may have paracrine and autocrine actions outside of the nervous system. Oxytocin and its receptor have been identified in the human prostate. The prostate is an androgen-dependent organ whose function is to secrete components of the seminal fluid. Oxytocin has been shown to modulate contractility of prostate tissue and also to regulate local concentrations of the biologically active androgens. Oxytocin has also been shown to regulate cell growth. Prostate disease is common and results from abnormal growth of the gland. Oxytocin concentrations are altered in both benign and malignant prostate diseases and in vitro studies suggest that the peptide may be involved in the pathophysiology of these diseases. PMID- 17725970 TI - Genetic and environmental contributions to prosocial behaviour in 2- to 9-year old South Korean twins. AB - Although over 50 twin and adoption studies have been performed on the genetic architecture of antisocial behaviour, far fewer studies have investigated prosocial behaviour, and none have done so on a non-western population. The present study examined mothers' ratings of prosocial behaviour in 514 pairs of 2- to 9-year-old South Korean monozygotic and dizygotic twins. Correlational analyses showed a tendency of increasing genetic effects and decreasing shared environmental effects with age although shared family environment effects and the moderating effects of age did not attain statistical significance in model fitting analyses. The best-fitting model indicated that 55% (95% CI: 45-64%) of the variance in the 2- to 9-year-olds' prosocial behaviour was due to genetic factors and 45% (95% CI: 36-55%) was due to non-shared environmental factors. It is concluded that genetic and environmental influences on prosocial behaviour in young South Koreans are mostly similar to those in western samples. PMID- 17725971 TI - Parental age difference and offspring count in humans. AB - Preferences for certain age characteristics of partners are reported across cultures: men prefer mates who are younger and women prefer mates older than themselves. To examine whether these age preferences entail fitness effects for men and women, we investigated the association among age differences between partners and offspring count. On the basis of a sample of approximately 10,000 post-reproductive Swedish men and women who did not change their partner between the birth of their first and last child, we find maximum offspring count in men if their partner is approximately 6 years younger, and in women if their partner is approximately 4 years older. We further find that after separation, on average, both men and women shift to a partner younger than the first, albeit in women the new partner is still older than the female herself. We conclude that the age preference for the partner yields fitness benefits for both men and women and may thus be an evolutionarily acquired trait. PMID- 17725972 TI - Antiviral treatment for the control of pandemic influenza: some logistical constraints. AB - Disease control programmes for an influenza pandemic will rely initially on the deployment of antiviral drugs such as Tamiflu, until a vaccine becomes available. However, such control programmes may be severely hampered by logistical constraints such as a finite stockpile of drugs and a limit on the distribution rate. We study the effects of such constraints using a compartmental modelling approach. We find that the most aggressive possible antiviral programme minimizes the final epidemic size, even if this should lead to premature stockpile run-out. Moreover, if the basic reproductive number R(0) is not too high, such a policy can avoid run-out altogether. However, where run-out would occur, such benefits must be weighed against the possibility of a higher epidemic peak than if a more conservative policy were followed. Where there is a maximum number of treatment courses that can be dispensed per day, reflecting a manpower limit on antiviral distribution, our results suggest that such a constraint is unlikely to have a significant impact (i.e. increasing the final epidemic size by more than 10%), as long as drug courses sufficient to treat at least 6% of the population can be dispensed per day. PMID- 17725974 TI - Culling-induced social perturbation in Eurasian badgers Meles meles and the management of TB in cattle: an analysis of a critical problem in applied ecology. AB - The Eurasian badger (Meles meles) is implicated in the transmission of bovine tuberculosis (TB) to cattle in the UK and Republic of Ireland. Badger culling has been employed for the control of TB in cattle in both countries, with varying results. Social perturbation of badger populations following culling has been proposed as an explanation for the failure of culling to consistently demonstrate significant reductions in cattle TB. Field studies indicate that culling badgers may result in increased immigration into culled areas, disruption of territoriality, increased ranging and mixing between social groups. Our analysis shows that some measures of sociality may remain significantly disrupted for up to 8 years after culling. This may have epidemiological consequences because previous research has shown that even in a relatively undisturbed badger population, movements between groups are associated with increases in the incidence of Mycobacterium bovis infection. This is consistent with the results from a large-scale field trial, which demonstrated decreased benefits of culling at the edges of culled areas, and an increase in herd breakdown rates in neighbouring cattle. PMID- 17725975 TI - Evolution of a single niche specialist in variable environments. AB - The pattern (space versus time) and scale (relative to the lifetime of individuals) of environmental variation is thought to play a central role in governing the evolution of the ecological niche and the maintenance of genetic variance in fitness. To evaluate this idea, we serially propagated an initially genetically uniform population of the bacterium Pseudomonas fluorescens for a few hundred generations in environments that differed in both the pattern and scale at which two highly contrasted carbon substrates were experienced. We found that, contrary to expectations, populations often evolved into a single niche specialist adapted to the less-productive substrate in variable environments and that the genetic variance in fitness across different components of the environment was not generally higher in variable environments when compared with constant environments. We provide evidence to suggest that our results reflect a novel constraint on niche evolution imposed by the supply of beneficial mutations available to selection in variable environments. PMID- 17725976 TI - Widespread endocrine disruption and reproductive impairment in an estuarine fish population exposed to seasonal hypoxia. AB - The long-term effects on marine fish populations of the recent increase worldwide in the incidence of coastal hypoxia are unknown. Here we show that chronic environmental exposure of Atlantic croaker (Micropogonias undulatus) to hypoxia in a Florida estuary caused marked suppression of ovarian and testicular growth which was accompanied by endocrine disruption. Laboratory hypoxia studies showed that the endocrine disruption was associated with impairment of reproductive neuroendocrine function and decreases in hypothalamic serotonin (5-HT) content and the activity of the 5-HT biosynthetic enzyme, tryptophan hydroxylase. Pharmacological restoration of hypothalamic 5-HT levels also restored neuroendocrine function, indicating that the stimulatory serotonergic neuroendocrine pathway is a major site of hypoxia-induced inhibition. Inhibition of tryptophan hydroxylase activity to downregulate reproductive activity could have evolved as an adaptive mechanism to survive periodic hypoxia, but in view of the recent increased incidence of coastal hypoxia could become maladaptive and potentially affect fish population abundance and threaten valuable fishery resources. PMID- 17725977 TI - Disentangling hybridization and host colonization in parasitic roundworms of humans and pigs. AB - Knowledge of cross-transmission and hybridization between parasites of humans and reservoir hosts is critical for understanding the evolution of the parasite and for implementing control programmes. There is now a consensus that populations of pig and human Ascaris (roundworms) show significant genetic subdivision. However, it is unclear whether this has resulted from a single or multiple host shift(s). Furthermore, previous molecular data have not been sufficient to determine whether sympatric populations of human and pig Ascaris can exchange genes. To disentangle patterns of host colonization and hybridization, we used 23 microsatellite loci to conduct Bayesian clustering analyses of individual worms collected from pigs and humans. We observed strong differentiation between populations which was primarily driven by geography, with secondary differentiation resulting from host affiliation within locations. This pattern is consistent with multiple host colonization events. However, there is low support for the short internal branches of the dendrograms. In part, the relationships among clusters may result from current hybridization among sympatric human and pig roundworms. Indeed, congruence in three Bayesian methods indicated that 4 and 7% of roundworms sampled from Guatemala and China, respectively, were hybrids. These results indicate that there is contemporary cross-transmission between populations of human and pig Ascaris. PMID- 17725979 TI - Songbirds use pulse tone register in two voices to generate low-frequency sound. AB - The principal physical mechanism of sound generation is similar in songbirds and humans, despite large differences in their vocal organs. Whereas vocal fold dynamics in the human larynx are well characterized, the vibratory behaviour of the sound-generating labia in the songbird vocal organ, the syrinx, is unknown. We present the first high-speed video records of the intact syrinx during induced phonation. The syrinx of anaesthetized crows shows a vibration pattern of the labia similar to that of the human vocal fry register. Acoustic pulses result from short opening of the labia, and pulse generation alternates between the left and right sound sources. Spontaneously calling crows can also generate similar pulse characteristics with only one sound generator. Airflow recordings in zebra finches and starlings show that pulse tone sounds can be generated unilaterally, synchronously or by alternating between the two sides. Vocal fry-like dynamics therefore represent a common production mechanism for low-frequency sounds in songbirds. These results also illustrate that complex vibration patterns can emerge from the mechanical properties of the coupled sound generators in the syrinx. The use of vocal fry-like dynamics in the songbird syrinx extends the similarity to this unusual vocal register with mammalian sound production mechanisms. PMID- 17725978 TI - Recent postglacial range expansion drives the rapid diversification of a songbird lineage in the genus Junco. AB - Pleistocene glacial cycles are thought to have played a major role in the diversification of temperate and boreal species of North American birds. Given that coalescence times between sister taxa typically range from 0.1 to 2.0 Myr, it has been assumed that diversification occurred as populations were isolated in refugia over long periods of time, probably spanning one to several full glacial cycles. In contrast, the rapid postglacial range expansions and recolonization of northern latitudes following glacial maxima have received less attention as potential promoters of speciation. Here we report a case of extremely rapid diversification in the songbird genus Junco as a result of a single continent wide range expansion within the last 10 000 years. Molecular data from 264 juncos sampled throughout their range reveal that as the yellow-eyed junco (Junco phaeonotus) of Mesoamerica expanded northward following the last glacial maximum, it speciated into the dark-eyed junco (Junco hyemalis), which subsequently diversified itself into at least five markedly distinct and geographically structured morphotypes in the USA and Canada. Patterns of low genetic structure and diversity in mitochondrial DNA and amplified fragment length polymorphism loci found in dark-eyed juncos relative to Mesoamerican yellow-eyed juncos provide support for the hypothesis of an expansion from the south, followed by rapid diversification in the north. These results underscore the role of postglacial expansions in promoting diversification and speciation through a mechanism that represents an alternative to traditional modes of Pleistocene speciation. PMID- 17725980 TI - Characterisation of workplaces with risks of internal exposures: air sampling. AB - The measurement of air samples may be used to assess risks of internal exposures, either by the use of workplace static air samplers (SAS) or personal air samplers (PAS). These measurements need to incorporate information on the physical and chemical nature of the aerosol, and the relationship between the sampled and potentially breathed aerosol. This paper provides an overview of methods, which are typically used in occupational dosimetry to determine these characteristics. A specific practical example is provided to illustrate how SAS are used to determine that potential personal doses are less than 1 mSv per year, and therefore do not require individual monitoring. The paper also discusses the nature and potential impact of the uncertainties associated with PAS monitoring, and how this is managed in practice. PMID- 17725981 TI - The effect of meloxicam, a selective COX-2 inhibitor, on the microvasculature of small metastatic liver tumors in rats. AB - BACKGROUND: COX-2 is involved in tumor angiogenesis and modulation of the production of angiogenetic factors by colorectal carcinoma cells. It has been shown that COX-2 inhibitors have inhibitory activities against various types of tumor, including colorectal carcinoma. In this study, we investigated the tumor vessels of small metastatic liver tumors in rats and the effect of meloxicam, a selective COX-2 inhibitor, on their growth and microvasculature. METHODS: The metastatic liver tumors were produced by intraportal inoculation of RCN-H4 cells in male F344/DuCrj rats (n = 40). The microvasculature was examined by scanning electron microscopy and stereomicroscopy. Microvascular casts were produced by perfusion via the abdominal aorta 14 days after tumor inoculation. Four groups (control, groups 1-3) of rats were treated with meloxicam 0, 0.6, 1.0 and 3.0 mg/kg/day, respectively, by oral gavage 5 days/week for two weeks from the day of inoculation of RCN-H4 cells. RESULTS: The mean number of tumors was significantly decreased in groups 1-3 (5.6+/-0.8 standard deviation, SD; 3.6+/-1.1; and 5.5+/ 1.1, respectively) compared with control (11.2+/-2.7; P = 0.0002, each). Meloxicam also significantly reduced the mean diameter of the tumor: 730+/-254, 685+/-212 and 644+/-139 in groups 1-3, respectively, in comparison with 870+/-276 in control (P = 0.0025, 0.0011 and <0.0001, respectively). CONCLUSIONS: Meloxicam's anti-angiogenic activity interferes with the growth of metastatic liver tumors. Meloxicam might have therapeutic potential for liver metastasis of colorectal carcinoma. PMID- 17725982 TI - Optimal design of oligonucleotide microarrays for measurement of DNA copy-number. AB - Copy-number variants (CNVs) occur frequently within the human genome, and may be associated with many human phenotypes. If disease association studies of CNVs are to be performed routinely, it is essential that the copy-number status be accurately genotyped. We systematically assessed the dynamic range response of an oligonucleotide microarray platform to accurately predict copy-number in a set of seven patients who had previously been shown to carry between 1 and 6 copies of an approximately 4 Mb region of 15q12.2-q13.1. We identify probe uniqueness, probe length, uniformity of probe melting temperature, overlap with SNPs and common repeats (particularly Alu elements) and guanine homopolymer content as parameters that significantly affect probe performance. Further, we prove the influence of these criteria on array performance by using these parameters to prospectively filter data from a second array design covering an independent genomic region and observing significant improvements in data quality. The informed selection of probes which have superior performance characteristics allows the prospective design of oligonucleotide arrays which show increased sensitivity and specificity compared with current designs. Although based on the analysis of data from comparative genomic hybridization experiments, we anticipate that our results are relevant to the design of improved oligonucleotide arrays for high-throughput copy-number genotyping of complex regions of the human genome. PMID- 17725984 TI - Expression, localization and tau exon 10 splicing activity of the brain RNA binding protein TNRC4. AB - Elucidating the mechanisms of alternative splicing in the brain is a prerequisite to the understanding of the pathogenesis of major neurological diseases linked to impairment of pre-mRNA alternative splicing. The gene trinucleotide repeat containing 4 (TNRC4) is predicted to encode a member of the CELF (CUG-BP- and ETR 3-like factors) family of RNA-binding proteins containing a 15-18-residue polyglutamine sequence. The TNRC4 transcript is selectively expressed in the brain. Using an anti-peptide antibody against the predicted sequence, we establish the presence of TNRC4 as a approximately 50 kDa protein in the brain. Full-length TNRC4 displays nuclear and cytoplasmic localizations in transfected cells, whereas a C-terminally truncated mutant is essentially confined to the cytoplasm. TNRC4 is not recruited into inclusions formed by polyglutamine expanded ataxin-1 or huntingtin. TNRC4 activates tau exon 10 (E10) inclusion at high efficiency in transfected cells. TNRC4 contains two consecutive N-terminal RNA recognition motifs (RRMs) separated from the C-terminal RRM. Deletion and point mutant analysis show that the activity of TNRC4 on tau E10 splicing is mainly mediated by the RNA-binding activity of the second RRM and involves an intronic element of the tau pre-mRNA. The polyglutamine sequence has no effect on the activity of TNRC4 on tau E10 splicing. This study represents the first characterization of TNRC4 and provides further insight into the mechanisms of brain-specific alternative splicing and their possible pathological implications. PMID- 17725983 TI - Familial amyotrophic lateral sclerosis-linked SOD1 mutants perturb fast axonal transport to reduce axonal mitochondria content. AB - Amyotrophic lateral sclerosis (ALS) is a late-onset neurological disorder characterized by death of motoneurons. Mutations in Cu/Zn superoxide dismutase-1 (SOD1) cause familial ALS but the mechanisms whereby they induce disease are not fully understood. Here, we use time-lapse microscopy to monitor for the first time the effect of mutant SOD1 on fast axonal transport (FAT) of bona fide cargoes in living neurons. We analyzed FAT of mitochondria that are a known target for damage by mutant SOD1 and also of membrane-bound organelles (MBOs) using EGFP-tagged amyloid precursor protein as a marker. We studied FAT in motor neurons derived from SOD1G93A transgenic mice that are a model of ALS and also in cortical neurons transfected with SOD1G93A and three further ALS-associated SOD1 mutants. We find that mutant SOD1 damages transport of both mitochondria and MBOs, and that the precise details of this damage are cargo-specific. Thus, mutant SOD1 reduces transport of MBOs in both anterograde and retrograde directions, whereas mitochondrial transport is selectively reduced in the anterograde direction. Analyses of the characteristics of mitochondrial FAT revealed that reduced anterograde movement involved defects in anterograde motor function. The selective inhibition of anterograde mitochondrial FAT enhanced their net retrograde movement to deplete mitochondria in axons. Mitochondria in mutant SOD1 expressing cells also displayed features of damage. Together, such changes to mitochondrial function and distribution are likely to compromise axonal function. These alterations represent some of the earliest pathological features so far reported in neurons of mutant SOD1 transgenic mice. PMID- 17725985 TI - The DNA polymerase gamma Y955C disease variant associated with PEO and parkinsonism mediates the incorporation and translesion synthesis opposite 7,8 dihydro-8-oxo-2'-deoxyguanosine. AB - Mitochondrial DNA is replicated and repaired by DNA polymerase gamma (pol gamma), encoded by the POLG gene. The Y955C substitution in POLG leads to autosomal dominant progressive external ophthalmoplegia (PEO) with other severe phenotypes. PEO patients with this mutation can further develop parkinsonism or premature ovarian failure. Mouse and yeast models with this mutation show enhanced amounts of oxidative lesions and increased mtDNA damage. In DNA pol gamma, Tyr955 plays a critical role in catalysis and high fidelity DNA synthesis. 7,8-dihydro-8-oxo-2' deoxyguanosine (8-oxo-dG) is one of the most common oxidative lesions in DNA and can promote transversion mutations. Mitochondria are thought to be a major source of endogenous reactive oxygen species that can react with dG to form 8-oxo-dG as one of the more common products. DNA polymerases can mitigate mutagenesis by 8 oxo-dG through allosteric interactions from amino acid side chains, which limit the anti-conformation of the 8-oxo-dG template base during translesion DNA synthesis. Here, we show that the Y955C pol gamma displays relaxed discrimination when either incorporating 8-oxo-dGTP or translesion synthesis opposite 8-oxo-dG. Molecular modeling and biochemical analysis suggest that this residue, Tyr955, in conjunction with Phe961 helps attenuate the anti-conformation in human pol gamma for error free bypass of 8-oxo-dG and substitution to Cys allows the mutagenic syn conformation. Collectively, these results offer a biochemical link between the observed oxidative stress in model systems and parkinsonism in patients, suggesting that patients harboring the Y955C POLG mutation may undergo enhanced oxidative stress and DNA mutagenesis. PMID- 17725986 TI - Genome-wide linkage analysis of 723 affected relative pairs with late-onset Alzheimer's disease. AB - Previous attempts to identify genetic loci conferring risk for late-onset Alzheimer's disease (LOAD) through linkage analysis have observed some regions of linkage in common. However, due to the sometimes-considerable overlap between the samples, some of these reports cannot be considered to be independent replications. In order to assess the strength of the evidence for linkage and to obtain the best indication of the location of susceptibility genes, we have amalgamated three large samples to give a total of 723 affected relative pairs (ARPs). Multipoint, model-free ARP linkage analysis was performed. Genome-wide significant evidence for linkage was observed on 10q21.2 (LOD=3.3) and genome wide suggestive evidence was observed on 9q22.33 (LOD=2.5) and 19q13.32 (LOD=2.0). One further region on 9p21.3 was identified with an LOD score>1. We observe no evidence to suggest that more than one locus is responsible for the linkage to 10q21.2, although this linked region may harbour more than one susceptibility gene. Evidence of allele-sharing heterogeneity between the original collection sites was observed on chromosome 9 but not on chromosome 10 or 19. Evidence for an interaction was observed between loci on chromosomes 10 and 19. Where samples overlapped, the genotyping consistency was high, estimated to average at 97.3%. Our large-scale linkage analysis consolidates clear evidence for a susceptibility locus for LOAD on 10q21.2. PMID- 17725987 TI - Functional correction of CNS lesions in an MPS-IIIA mouse model by intracerebral AAV-mediated delivery of sulfamidase and SUMF1 genes. AB - Mucopolysaccharidosis type IIIA (MPS-IIIA or Sanfilippo syndrome) is a lysosomal storage disorder caused by the congenital deficiency of sulfamidase (SGSH) enzyme and consequent accumulation of partially degraded heparan sulfate (HS) in lysosomes. The central nervous system (CNS) is the predominant site of tissue damage in MPS-IIIA. Here we describe a gene therapy approach for MPS-IIIA in a mouse model using recombinant adeno-associated virus serotype 5 (AAV2/5) as a vehicle to deliver therapeutic genes to the CNS. SUMF1 (SUlfatase Modifying Factor 1) exhibits an enhancing effect on sulfatase activity when co-expressed with sulfatases. Consistent with these findings, we demonstrated that co-delivery of SUMF1 and SGSH (via an AAV2/5-CMV-SGSH-IRES-SUMF1 vector) resulted in a synergistic increase in SGSH activity, both in primary neural cells and in murine brain. A study aimed at testing the therapeutic efficacy of simultaneous brain administration of SUMF1 and SGSH was then performed by injecting the lateral ventricles of newborn MPS-IIIA/normal mice with either AAV2/5-CMV-SGSH-IRES-SUMF1 or AAV2/5-CMV-GFP vectors. Widespread GFP expression was observed within the GFP injected brain, and a stable and significant increase of SGSH activity was detected in several brain regions following SGSH-IRES-SUMF1 administration. Treatment with AAV2/5-CMV-SGSH-IRES-SUMF1 vectors resulted in a visible reduction in lysosomal storage and inflammatory markers in transduced brain regions. Finally, the MPS-IIIA mice treated with therapeutic genes displayed an improvement in both motor and cognitive functions. Our results suggest that early treatment of CNS lesions by AAV-mediated intraventricular injection of both SGSH and SUMF1 genes may represent a feasible therapy for MPS-IIIA. PMID- 17725988 TI - Isolation of germ cells from leukemic cells. PMID- 17725989 TI - Exposure to organic solvents and adverse pregnancy outcomes. AB - BACKGROUND: Organic solvents are among the most common exposures in the workplace. Our objective was to elaborate the relationship between prenatal occupational solvent exposure and fetal growth as well as duration of pregnancy, and to quantify the impact of occupational organic solvent exposure. METHODS: We conducted a population-based study of 1670 singleton newborns of women who participated in The Finnish Prenatal Environment and Health Study after their delivery (response rate 94%) and who were working during pregnancy (65%). Exposure information was based on questions about exposure to solvents at work before and during pregnancy. The health outcomes, based on information from a questionnaire and the Finnish Medical Birth Registry, were low birth weight (<3000 g), small-for-gestational-age and preterm delivery (<37 weeks). RESULTS: In logistic regression analysis, the risk of the baby being small-for-gestational age was related to any exposure to solvents 3 months before or during pregnancy with an adjusted odds ratio (OR) of 1.67 [95% confidence interval (CI) = 1.02 2.73]. Also the adjusted OR for low birth weight was elevated with exposure, although it did not reach statistical significance (1.17; 95% CI = 0.71-1.93). The population attributable fraction for small-for-gestational-age was 2.3% for all pregnant women. CONCLUSIONS: Work exposure to organic solvents may reduce intrauterine growth by increasing the risk of the baby being small-for gestational-age. PMID- 17725990 TI - Oxygen concentration during mouse oocyte in vitro maturation affects embryo and fetal development. AB - BACKGROUND: Little is known of how the oxygen environment in the ovarian follicle affects oocyte and embryo development, but this has an important impact on the conditions used for in vitro maturation (IVM) of oocytes. We investigated the effect of varying oxygen concentrations during IVM on subsequent pre and post implantation development. METHODS: IVM of mouse cumulus-oocyte complexes (COCs) was performed under 2, 5, 10 or 20% O(2) (6% CO(2), balance N(2)). In vivo matured COCs were collected post ovulation. Embryos were generated by IVF and culture. Blastocyst development, cell number and apoptosis were assessed, and fetal and placental outcomes analysed following embryo transfer at day 18 of pregnancy. RESULTS: Oxygen concentration during IVM did not affect oocyte maturation or subsequent fertilization, cleavage and blastocyst development rates. Maturation of oocytes under 2% O(2) increased blastocyst trophectoderm cell number compared with all groups and numbers at 5% were higher than 20% (both P < 0.05). Percentage of apoptotic cells was increased in blastocysts developed from 2% O(2)-matured oocytes, compared with maturation at 5% O(2) or in vivo (P < 0.05). Rates of embryo implantation and development into a viable fetus were not altered by IVM oxygen. However, fetal weight was reduced following oocyte maturation at 5% O(2) compared wiht 20% O(2) and maturation at 5% O(2) also reduced placental weight, when compared with in vivo-matured oocytes (both P < 0.05). CONCLUSIONS: Level of O(2) exposure during oocyte maturation can alter the cellular composition of blastocysts, but these changes in cell number do not correlate with the altered fetal and placental outcomes after transfer. PMID- 17725992 TI - Forward to the special issue on the prefrontal cortex and working memory: in memory of Patricia S. Goldman-Rakic. PMID- 17725991 TI - Stimulatory and inhibitory effects of genistein on human uterine leiomyoma cell proliferation are influenced by the concentration. AB - BACKGROUND: Due to dietary exposure of women to genistein, a soy-derived phytoestrogen, and the estrogen responsiveness of uterine leiomyomas 'fibroids', we evaluated the effects of genistein (0.001-50 microg/ml) on human uterine leiomyoma (UtLM) cells versus uterine smooth muscle cells (UtSMCs) in vitro. METHODS: Light microscopy was used to determine the effects of genistein on cell morphology. Proliferation was assessed using a colorimetric assay and proliferating cell nuclear antigen (PCNA) immunocytochemistry. Flow cytometry was used to quantitate cells in the S-phase and those undergoing apoptosis. A fluorometric assay and confocal microscopy were used to detect caspase-3 activity and apoptotic bodies, respectively. RESULTS: In UtLM cells, low concentrations (< or = 1 microg/ml) of genistein stimulated proliferation, increased PCNA labeling and the percentage of cells in the S-phase, but this did not occur in UtSMCs. Higher concentrations (> or = 10 microg/ml) of genistein adversely affected the morphology, significantly inhibited proliferation, decreased PCNA labeling, increased caspase-3 activity and induced apoptosis in both cell types. CONCLUSIONS: Genistein's effects are concentration-dependent in both cell lines. Lower concentrations elicit proliferative effects on UtLM cells only; whereas, higher concentrations alter morphology, inhibit proliferation, and increase caspase activity and apoptosis in both cell types, with the latter two effects being more extensive in UtSMCs. PMID- 17725993 TI - Integration of cognitive and motivational context information in the primate prefrontal cortex. AB - The prefrontal cortex (PFC) appears to be important for processing both cognitive and motivational context information. Primate lateral PFC (LPFC) neurons are involved in cognitive context-dependent stimulus coding by responding differently to an identical stimulus according to the task situation. Such context-dependent LPFC activity appears to be supported by context-representing activity, observed also in LPFC neurons, in which the baseline activity differs as a function of the task. In LPFC, there are also neurons that code stimulus on the basis of motivational context. This motivational context is represented in differential baseline activity as a function of the reward context. In the orbitofrontal cortex (OFC), there are neurons that code stimuli depending on the motivational context as well as neurons that represent motivational context information. Furthermore, we found LPFC neurons that coded the stimulus depending on both the cognitive and motivational context, as well as LPFC neurons that represented both the cognitive and motivational context. For adaptive behavior, it is important to code the meaning of the environmental situation based on the context. While OFC is predominantly concerned with processing motivational context information, LPFC seems to play important roles in integrating the cognitive and motivational context for adaptive goal-directed behavior. PMID- 17725994 TI - The role of working memory representations in the control of attention. AB - Previous research suggests that target templates are stored visual working memory and used to guide attention during visual search. However, observers can search efficiently even if working memory is filled to capacity by a concurrent task. The idea that target templates are stored in working memory receives support primarily from studies of nonhuman primates in which the target varies from trial to trial, and it is possible that working memory templates are not necessary when target identity remains constant, as in most studies of visual search in humans. To test this hypothesis, we asked subjects to perform a visual search task during the delay interval of a visual working memory task. The 2 tasks were found to interfere with each other when the search targets changed from trial to trial, but not when target identity remained constant. Thus, a search template is stored in visual working memory only when the target varies from trial to trial. These findings suggest that the network of brain areas involved in shifting attention during visual search tasks may be able to operate essentially independently of the anatomical areas that perform visual working memory maintenance of objects, but only if the identity of the visual search target is stable across time. PMID- 17725996 TI - Specificity in inhibitory systems associated with prefrontal pathways to temporal cortex in primates. AB - The prefrontal cortex selects relevant signals and suppresses irrelevant stimuli for a given task through mechanisms that are not understood. We addressed this issue using as a model system the pathways from the functionally distinct prefrontal areas 10 and 32 to auditory association cortex, and investigated their relationship to inhibitory neurons labeled for calbindin (CB) or parvalbumin (PV), which differ in mode of inhibition. Projection neurons in area 10 originated mostly in layers 2-3 and were intermingled with CB inhibitory neurons. In contrast, projections from area 32 originated predominantly in layers 5-6 among PV inhibitory neurons. Prefrontal axonal boutons terminating in layers 2-3 of auditory association cortex were larger than those terminating in layer 1. Most prefrontal axons synapsed on spines of excitatory neurons but a significant number targeted dendritic shafts of inhibitory neurons. Axons from area 10 targeted CB and PV inhibitory neurons, whereas axons from area 32 targeted PV inhibitory neurons. The preferential association of the 2 prefrontal pathways with distinct classes of inhibitory neurons at their origin and termination may reflect the specialization of area 10 in working memory functions and area 32 in emotional communication. These findings suggest diversity in inhibitory control by distinct prefrontal pathways. PMID- 17725995 TI - Functional interactions between prefrontal and visual association cortex contribute to top-down modulation of visual processing. AB - Attention-dependent modulation of neural activity in visual association cortex (VAC) is thought to depend on top-down modulatory control signals emanating from the prefrontal cortex (PFC). In a previous functional magnetic resonance imaging study utilizing a working memory task, we demonstrated that activity levels in scene-selective VAC (ssVAC) regions can be enhanced above or suppressed below a passive viewing baseline level depending on whether scene stimuli were attended or ignored (Gazzaley, Cooney, McEvoy, et al. 2005). Here, we use functional connectivity analysis to identify possible sources of these modulatory influences by examining how network interactions with VAC are influenced by attentional goals at the time of encoding. Our findings reveal a network of regions that exhibit strong positive correlations with a ssVAC seed during all task conditions, including foci in the left middle frontal gyrus (MFG). This PFC region is more correlated with the VAC seed when scenes were remembered and less correlated when scenes were ignored, relative to passive viewing. Moreover, the strength of MFG-VAC coupling correlates with the magnitude of attentional enhancement and suppression of VAC activity. Although our correlation analyses do not permit assessment of directionality, these findings suggest that PFC biases activity levels in VAC by adjusting the strength of functional coupling in accordance with stimulus relevance. PMID- 17725997 TI - Differential regulation of fronto-executive function by the monoamines and acetylcholine. AB - The prefrontal cortex (PFC) is innervated by the monoamines, dopamine (DA), noradrenaline (NA), and serotonin, as well as acetylcholine, and the marked influence of these neurochemical systems on prefrontal working memory processes has been widely described. However, their potentially, differential contribution to prefrontal functioning is less well understood. This paper reviews evidence to support the hypothesis that these neurochemical systems recruit distinct fronto executive operations. Direct comparison of the effects of manipulations of these neuromodulators within PFC on performance of an attentional set-shifting paradigm reveals their differential contribution to distinct task stages. Depletion of prefrontal serotonin selectively disrupts reversal learning but not attentional set formation or set shifting. In contrast, depletion of prefrontal DA disrupts set formation but not reversal learning. NA depletion on the other hand specifically impairs set-shifting, whereas its effects on reversal learning remain unclear. Finally, depletion of prefrontal acetylcholine has no effect on either set formation or set shifting but impairs serial reversal learning. Because these neurochemical systems are known to represent distinct states of stress, arousal, attention, and affect, it is postulated that they augment the different types of executive operation that are recruited and performed within these states via a synergistic interaction with the PFC. PMID- 17725998 TI - Cannabinoid-mediated disinhibition and working memory: dynamical interplay of multiple feedback mechanisms in a continuous attractor model of prefrontal cortex. AB - Recurrent excitation is believed to underlie persistent neural activity observed in the prefrontal cortex and elsewhere during working memory. However, other positive and negative feedback mechanisms, operating on disparate timescales, may also play significant roles in determining the behavior of a working memory circuit. In this study, we examined dynamical interactions of multiple feedback mechanisms in a biophysically based neural model of spatial working memory. In such continuous attractor networks, a self-sustained activity pattern tends to drift randomly, resulting in a decreased accuracy of memory over time. Moreover, attractor states become unstable when spike-frequency adaptation reduces the excitability of persistently firing pyramidal neurons. Here, we show that a slow activity-dependent local disinhibition, namely cannabinoid-dependent depolarization-induced suppression of inhibition (DSI), can counteract these destabilizing effects, rendering working memory function more robust. In addition, the slow DSI effect gives rise to trial-to-trial correlations of memory guided behavioral responses. On the other hand, computer simulations revealed that a global cannabinoid agonist (mimicking the effect of drug intake) yields the opposite effect. Thus, this work suggests a circuit scenario according to which endogenous DSI is beneficial for, whereas an exogenous drug such as marijuana is detrimental to, working memory and possibly other prefrontal functions. PMID- 17726000 TI - Dysfunctional and compensatory prefrontal cortical systems, genes and the pathogenesis of schizophrenia. AB - Cognitive deficits are critical determinants of schizophrenia morbidity. In this review, we offer a mechanistic perspective regarding schizophrenia-related changes observed in prefrontal cortical networks engaged in working memory. A body of earlier work converges on aberrations in putative macrocircuit stability and functional efficiency as the underlying pathophysiology of the cognitive deficits in schizophrenia. In parsing the dysfunctional prefrontal cortical dynamics of schizophrenia, recent functional magnetic resonance imaging and electoencephalography works suggest that in the context of reduced capacity for executive aspects of working memory, patients engage a larger network of cortical regions consistent with an interplay between reduced signal-to-noise components and the recruitment of compensatory networks. The genetic programming underlying these systems-level cortical interactions has been examined under the lens of certain schizophrenia susceptibility genes, especially catechol-o methyltransferase (COMT) and GRM3. Variation in COMT, which presumably impacts on cortical dopamine signaling, translates into variable neural strategies for working memory and altering patterns of intracortical functional correlations. GRM3, which impacts on synaptic glutamate, interacts with COMT and exaggerates the genetic dissection of cortical processing strategies. These findings reveal novel insights into the modulation and parcellation of working memory processing in cortical assemblies and provide a mechanistic link between susceptibility genes and cortical pathophysiology related to schizophrenia. PMID- 17726001 TI - Ventrolateral prefrontal neuronal activity related to active controlled memory retrieval in nonhuman primates. AB - It is controversial whether monkeys, like human subjects, can recall, upon instruction, specific information about an event in memory. We therefore tested macaque monkeys on a task that was originally developed to study such active controlled memory retrieval in human subjects and we were able to demonstrate that monkeys, like human subjects, can retrieve, upon command, specific components of previously encoded events. Furthermore, following earlier functional neuroimaging work with human subjects showing the mid-ventrolateral prefrontal cortex to be involved in such active controlled retrieval, we recorded single-neuron activity within this region of the monkey brain while the monkeys performed the active retrieval task. Neuronal responses were related to the retrieval and the decision whether the retrieved information was the instructed one. These findings demonstrate, for the first time, an impressive capacity by macaque monkeys for controlled memory retrieval and, in addition, provide neurophysiological evidence about the role of the mid-ventrolateral prefrontal cortex in such controlled retrieval. PMID- 17725999 TI - Consequences of variations in genes that affect dopamine in prefrontal cortex. AB - Patricia Goldman-Rakic played a groundbreaking role in investigating the cognitive functions subserved by dorsolateral prefrontal cortex and the key role of dopamine in that. The work discussed here builds on that including: 1) Studies of children predicted to have lower levels of prefrontal dopamine but otherwise basically normal brains (children treated for phenylketonuria [PKU]). Those studies changed medical guidelines, improving the children's lives. 2) Studies of visual impairments (in contrast sensitivity and motion perception) in PKU children due to reduced retinal dopamine and due to excessive phenylalanine during the first postnatal weeks. Those studies, too, changed medical guidelines. 3) Studies of working memory and inhibitory control differences in typically developing children due to differences in catechol-O-methyltransferase (COMT) genotype, which selectively affect prefrontal dopamine levels. 4) Studies of gender differences in the effect of COMT genotype on cognitive performance in older adults. 5) A hypothesis about fundamental differences between attention deficit hyperactivity disorder (ADHD) that includes hyperactivity and ADHD of the inattentive type. Those disorders are hypothesized to differ in the affected neural system, underlying genetics, responsiveness to medication, comorbidities, and cognitive and behavioral profiles. These sound quite disparate but they all grew systematically out the base laid down by Patricia Goldman-Rakic. PMID- 17726003 TI - The representation of multiple objects in prefrontal neuronal delay activity. AB - The ability to retain multiple items in short-term memory is fundamental for intelligent behavior, yet little is known about its neural basis. To explore the mechanisms underlying this ability, we trained 2 monkeys to remember a sequence of 2 objects across a short delay. We then recorded the activity of neurons from the lateral prefrontal cortex during task performance and found that most neurons had activity that depended on the identity of both objects while a minority reflected just one object. Further, the activity driven by a particular combination of objects was not a simple addition of the activity elicited by individual objects. Instead, the representation of the first object was altered by the addition of the second object to memory, and the form of this change was not systematically predictable. These results indicate that multiple objects are not stored in separate groups of prefrontal neurons. Rather, they are represented by a single population of neurons in a complex fashion. We also found that the strength of the memory trace associated with each object decayed over time, leading to a relatively stronger representation of more recently seen objects. This is a potential mechanism for representing the temporal order of objects. PMID- 17726004 TI - An information-theoretical approach to contextual processing in the human brain: evidence from prefrontal lesions. AB - Context shapes perception, thought, and action, but little is known about the neural mechanisms supporting these modulations. Here, we addressed the role of lateral prefrontal cortex (PFC) in context updating and maintenance from an information-theoretic perspective. Ten patients with PFC lesions and 10 age matched controls responded to bilaterally displayed visual targets intermixed with repetitive and novel distracters in 2 different task contexts. In a predictable context, targets were always preceded by a novel event, whereas this temporal contingency was removed in an unpredictable context condition. We applied information theory to the analysis and interpretation of behavioral and electrophysiological data. The results revealed deficits in both the selection and the suppression of familiar versus novel information mainly observed at the visual hemifield contralateral to PFC damage due to disrupted frontocortical and frontosubcortical connectivity. The findings support a deficit in the representation of the temporal contingency between contextually related novel and familiar stimulation subsequent to lateral PFC damage. PMID- 17726005 TI - Persistent discharges in the prefrontal cortex of monkeys naive to working memory tasks. AB - Neurons in the prefrontal cortex and a network of interconnected brain areas discharge in a persistent fashion after the offset of sensory stimulation. Such persistent discharges are thought to constitute a neuronal correlate of working memory. The information content of neuronal discharges and its anatomical localization across the surface of the prefrontal cortex has been a matter of debate. Discrepant results by different laboratories may be due to the effects of different training regiments and tasks used in memory tasks. In order to address how training in a memory task alters neuronal responses, we performed recordings in monkeys that were never trained in memory tasks, but passively viewed visual stimuli. We have found that a population of prefrontal neurons responded to visual stimuli and also exhibited significantly elevated responses during "delay" intervals of the task. For a population of these neurons, persistent discharges were selective for the location and feature of the preceding stimulus. These discharges were typically disrupted by the appearance of a subsequent stimulus. Our results suggest that some prefrontal neurons represent the location and identity of visual stimuli in a persistent fashion, even when the latter are not behaviorally important or required to be kept in memory. PMID- 17726006 TI - Prefrontal delay-period activity reflects the decision process of a saccade direction during a free-choice ODR task. AB - To examine how delay-period activity participates in the decision of a saccade direction, we analyzed prefrontal activity while monkeys performed 2 tasks: oculomotor delayed-response (ODR) and self-selection ODR (S-ODR) tasks. In the ODR task, monkeys were required to make a memory-guided saccade to the cue location after a 3-s delay. In the S-ODR task, 4 identical visual cues were presented simultaneously during the cue period and monkeys were required to make a saccade in any one direction after the delay. Delay-period activity was observed in both tasks in the same neuron with similar directional preferences. Neurons with delay-period activity were classified into several groups based on the temporal pattern of the activity itself and of the strength of the directional selectivity. Among these, neurons with an increasing type of delay period activity with persistent directional selectivity throughout the delay period in the ODR task also showed directional delay-period activity in the S-ODR task. These results indicate that an increasing type of delay-period activity, which is thought to represent motor information, plays an important role in generating and enhancing directional bias in the S-ODR task and therefore contributes significantly to the decision process of the saccade direction in the S-ODR task. PMID- 17726007 TI - Identification of a novel lysophospholipid acyltransferase in Saccharomyces cerevisiae. AB - The incorporation of unsaturated acyl chains into phospholipids during de novo synthesis is primarily mediated by the 1-acyl-sn-glycerol-3-phosphate acyltransferase reaction. In Saccharomyces cerevisiae, Slc1 has been shown to mediate this reaction, but distinct activity remains after its removal from the genome. To identify the enzyme that mediates the remaining activity, we performed synthetic genetic array analysis using a slc1Delta strain. One of the genes identified by the screen, LPT1, was found to encode for an acyltransferase that uses a variety of lysophospholipid species, including 1-acyl-sn-glycerol-3 phosphate. Deletion of LPT1 had a minimal effect on 1-acyl-sn-glycerol-3 phosphate acyltransferase activity, but overexpression increased activity 7-fold. Deletion of LPT1 abrogated the esterification of other lysophospholipids, and overexpression increased lysophosphatidylcholine acyltransferase activity 7-fold. The majority of this activity co-purified with microsomes. To test the putative role for this enzyme in selectively incorporating unsaturated acyl chains into phospholipids in vitro, substrate concentration series experiments were performed with the four acyl-CoA species commonly found in yeast. Although the saturated palmitoyl-CoA and stearoyl-CoA showed a lower apparent Km, the monounsaturated palmitoleoyl-CoA and oleoyl-CoA showed a higher apparent Vmax. Arachidonyl-CoA, although not abundant in yeast, also had a high apparent Vmax. Pulse-labeling of lpt1Delta strains showed a 30% reduction in [3H]oleate incorporation into phosphatidylcholine only. Therefore, Lpt1p, a member of the membrane-bound o acyltransferase gene family, seems to work in conjunction with Slc1 to mediate the incorporation of unsaturated acyl chains into the sn-2 position of phospholipids. PMID- 17726008 TI - MEKK4 stimulation of p38 and JNK activity is negatively regulated by GSK3beta. AB - The MAPK kinase kinase MEKK4 is required for neurulation and skeletal patterning during mouse development. MEKK4 phosphorylates and activates MKK4/MKK7 and MKK3/MKK6 leading to the activation of JNK and p38, respectively. MEKK4 is believed to be auto-inhibited, and its interaction with other proteins controls its dimerization and activation. TRAF4, GADD45, and Axin each bind and activate MEKK4, with TRAF4 and Axin binding to the kinase domain and GADD45 binding within the N-terminal regulatory domain. Here we show that similar to the interaction with TRAF4 and Axin, the kinase domain of MEKK4 interacts with the multifunctional serine/threonine kinase GSK3beta. GSK3beta binding to MEKK4 blocks MEKK4 dimerization that is required for MEKK4 activation, effectively inhibiting MEKK4 stimulation of the JNK and p38 MAPK pathways. Inhibition of GSK3beta kinase activity with SB216763 results in enhanced MEKK4 kinase activity and increased JNK and p38 activation, indicating that an active state of GSK3beta is required for binding and inhibition of MEKK4 dimerization. Furthermore, GSK3beta phosphorylates specific serines and threonines in the N terminus of MEKK4. Together, these findings demonstrate that GSK3beta binds to the kinase domain of MEKK4 and regulates MEKK4 dimerization. However, unlike TRAF4, Axin, and GADD45, GSK3beta inhibits MEKK4 activity and prevents its activation of JNK and p38. Thus, control of MEKK4 dimerization is regulated both positively and negatively by its interaction with specific proteins. PMID- 17726009 TI - Glycosaminoglycans facilitate procathepsin B activation through disruption of propeptide-mature enzyme interactions. AB - Lysosomal cysteine cathepsin B participates in numerous diverse cellular processes. In acquiring its activity, the proregion, which blocks the substrate binding site in the proenzyme, needs to be cleaved off. Here we demonstrate that polyanionic polysaccharides, glycosaminoglycans (GAGs), can accelerate the autocatalytic removal of the propeptide and subsequent activation of cathepsin B. We show that naturally occurring GAGs such as chondroitin sulfates and heparin, as well as the synthetic analog dextran sulfate, accelerate the processing in a concentration-dependent manner. Heparin oligosaccharides down to the size of tetrasaccharides were efficient in accelerating the procathepsin B processing, whereas disaccharides were without effect. Further, the ability of the GAGs to accelerate procathepsin B processing was sensitive to increasing NaCl concentrations, indicating that electrostatic interaction between the GAGs and procathepsin B are operative in the accelerating effect. Also the processing of the catalytic procathepsin B mutant by wild type cathepsin B was enhanced in the presence of GAGs, suggesting that GAGs induce a conformational change in procathepsin B, converting it into a better substrate. Site-directed mutagenesis showed that His(28), Lys(39), and Arg(40), located within the procathepsin B propeptide, have significant roles in the acceleration of procathepsin B activation induced by short GAGs. Because procathepsin B and GAGs often co localize in vivo, we propose that GAGs may play a physiological role in the activation of procathepsin B. PMID- 17726010 TI - Y box-binding protein-1 binds to the dengue virus 3'-untranslated region and mediates antiviral effects. AB - Dengue virus, a member of the family Flaviviridae, poses a serious public health threat worldwide. Dengue virus is a positive-sense RNA virus that harbors a genome of approximately 10.7 kb. Replication of dengue virus is mediated coordinately by cis-acting genomic sequences, viral proteins, and host cell factors. We have isolated and identified several host cell factors from baby hamster kidney cell extracts that bind with high specificity and high affinity to sequences within the untranslated regions of the dengue virus genome. Among the factors identified, Y box-binding protein-1 (YB-1) and the heterogeneous nuclear ribonucleoproteins (hnRNPs), hnRNP A1, hnRNP A2/B1, and hnRNP Q, bind to the dengue virus 3'-untranslated region. Further analysis indicated that YB-1 binds to the dengue virus 3' stem loop, a conserved structural feature located at the 3' terminus of the 3'-untranslated region of many flaviviruses. Analysis of the impact of YB-1 on replication of dengue virus in YB-1+/+ and YB-1-/- mouse embryo fibroblasts indicated that host YB-1 mediates an antiviral effect. Further studies demonstrated that this antiviral impact is due, at least in part, to a repressive role of YB-1 on dengue virus translation via a mechanism that requires viral genomic sequences. These results suggest a novel role for YB-1 as an antiviral host cell factor. PMID- 17726011 TI - A covalent inhibitor targeting an intermediate conformation of the fusogenic subunit of the HIV-1 envelope complex. AB - Peptide inhibitors corresponding to sequences in the six helix bundle structure of the fusogenic portion (gp41) of the HIV envelope glycoprotein have been successfully implemented in preventing HIV entry. These peptides bind to regions in HIV gp41 transiently exposed during the fusion reaction. In an effort to improve upon these entry inhibitors, we have successfully designed and tested peptide analogs composed of chemical spacers and reactive moieties positioned strategically to facilitate covalent attachment. Using a temperature-arrested state prime wash in vitro assay we show evidence for the trapping of a pre-six helix bundle fusion intermediate by a covalent reaction with the specific anti HIV-1 peptide. This is the first demonstration of the trapping of an intermediate conformation of a viral envelope glycoprotein during the fusion process that occurs in live cells. The permanent specific attachment of the covalent inhibitor is projected to improve the pharmacokinetics of administration in vivo and thereby improve the long-term sustainability of peptide entry inhibitor therapy and help to expand its applicability beyond salvage therapy. PMID- 17726012 TI - Escherichia coli signal recognition particle receptor FtsY contains an essential and autonomous membrane-binding amphipathic helix. AB - Escherichia coli membrane protein biogenesis is mediated by a signal recognition particle and its membrane-associated receptor (FtsY). Although crucial for its function, it is still not clear how FtsY interacts with the membrane. Analysis of the structure/function differences between severely truncated active (NG+1) and inactive (NG) mutants of FtsY enabled us to identify an essential membrane interacting determinant. Comparison of the three-dimensional structures of the mutants, combined with site-directed mutagenesis, modeling, and liposome-binding assays, revealed that FtsY contains a conserved autonomous lipid-binding amphipathic alpha-helix at the N-terminal end of the N domain. Deletion experiments showed that this helix is essential for FtsY function in vivo, thus offering, for the first time, clear evidence for the functionally important, physiologically relevant interaction of FtsY with lipids. PMID- 17726013 TI - Membrane targeting of ribosomes and their release require distinct and separable functions of FtsY. AB - The mechanism underlying the interaction of the Escherichia coli signal recognition particle (SRP) receptor FtsY with the cytoplasmic membrane is not fully understood. We investigated this issue by utilizing active (NG+1) and inactive (NG) mutants of FtsY. In solution, the mutants comparably bind and hydrolyze nucleotides and associate with SRP. In contrast, a major difference was observed in the cellular distribution of NG and NG+1. Unlike NG+1, which distributes almost as the wild-type receptor, the inactive NG mutant accumulates on the membrane, together with ribosomes and SRP. The results suggest that NG function is compromised only at a later stage of the targeting pathway and that despite their identical behavior in solution, the membrane-bound NG-SRP complex is less active than NG+1-SRP. This notion is strongly supported by the observation that lipids stimulate the GTPase activity of NG+1-SRP, whereas no stimulation is observed with NG-SRP. In conclusion, we propose that the SRP receptor has two distinct and separable roles in (i) mediating membrane targeting and docking of ribosomes and (ii) promoting their productive release from the docking site. PMID- 17726015 TI - Role of the alpha-helix 163-170 in factor Xa catalytic activity. AB - Factor Xa (FXa) is a key protease of the coagulation pathway whose activity is known to be in part modulated by binding to factor Va (FVa) and sodium ions. Previous investigations have established that solvent-exposed, charged residues of the FXa alpha-helix 163-170 (h163-170), Arg(165) and Lys(169), participate in its binding to FVa. In the present study we aimed to investigate the role of the other residues of h163-170 in the catalytic functions of the enzyme. FX derivatives were constructed in which point mutations were made or parts of h163 170 were substituted with the corresponding region of either FVIIa or FIXa. Purified FXa derivatives were compared with wild-type FXa. Kinetic studies in the absence of FVa revealed that, compared with wild-type FXa, key functional parameters (catalytic activity toward prothrombin and tripeptidyl substrates and non-enzymatic interaction of a probe with the S1 site) were diminished by mutations in the NH(2)-terminal portion of h163-170. The defective amidolytic activity of these FXa derivatives appears to result from their impaired interaction with Na(+) because using a higher Na(+) concentration partially restored normal catalytic parameters. Furthermore, kinetic measurements with tripeptidyl substrates or prothrombin indicated that assembly of these FXa derivatives with an excess of FVa in the prothrombinase complex improves their low catalytic efficiency. These data indicate that residues in the NH(2)-terminal portion of the FVa-binding h163-170 are energetically linked to the S1 site and Na(+)-binding site of the protease and that residues Val(163) and Ser(167) play a key role in this interaction. PMID- 17726014 TI - Myeloperoxidase inactivates TIMP-1 by oxidizing its N-terminal cysteine residue: an oxidative mechanism for regulating proteolysis during inflammation. AB - An imbalance between the proteolytic activity of matrix metalloproteinases (MMPs) and the activity of tissue inhibitors of metalloproteinases (TIMPs) is implicated in tissue injury during inflammation. The N-terminal cysteine of TIMP-1 plays a key role in the inhibitory activity of the protein because it coordinates the essential catalytic Zn2+ of the MMP, preventing the metal ion from functioning. An important mechanism for controlling the interaction of TIMPs with MMPs might involve hypochlorous acid (HOCl), a potent oxidant produced by the myeloperoxidase (MPO) system of phagocytes. Here, we show that HOCl generated by the MPO-H2O2-chloride system inactivates TIMP-1 by oxidizing its N-terminal cysteine. The product is a novel 2-oxo acid. Liquid chromatography-mass spectrometry and tandem mass spectrometry analyses demonstrated that methionine and N-terminal cysteine residues were rapidly oxidized by MPO-derived HOCl but only oxidation of the N-terminal cysteine of TIMP-1 correlated well with loss of inhibitory activity. Importantly, we detected the signature 2-oxo-acid N-terminal peptide in tryptic digests of bronchoalveolar lavage fluid from patients with acute respiratory distress syndrome, demonstrating that TIMP-1 oxidation occurs in vivo. Loss of the N-terminal amino group and disulfide structure are crucial for preventing TIMP-1 from inhibiting MMPs. Our findings suggest that pericellular production of HOCl by phagocytes is a pathogenic mechanism for impairing TIMP-1 activity during inflammation. PMID- 17726016 TI - Akt phosphorylates MstI and prevents its proteolytic activation, blocking FOXO3 phosphorylation and nuclear translocation. AB - Oxidative stress can induce apoptosis through activation of MstI, subsequent phosphorylation of FOXO and nuclear translocation. MstI is a common component of apoptosis initiated by various stresses. MstI kinase activation requires autophosphorylation and proteolytic degradation by caspases. The role of Akt in regulating MstI activity has not been previously examined. Here, we show that MstI is a physiological substrate of Akt. Akt phosphorylation of MstI diminishes its apoptotic cleavage by caspases and prevents its kinase activity on FOXO3. MstI directly binds to Akt, which is regulated Akt kinase activity. Akt phosphorylates MstI on the Thr(387) residue and protects MstI from apoptotic cleavage in vitro and in apoptotic cells. Interestingly, Akt phosphorylation of MstI strongly inhibits its kinase activity on FOXO3. The phosphorylation mimetic mutant MST1 T387E blocks H2O2-triggered FOXO3 nuclear translocation and apoptosis. Thus, our findings support that Akt blocks MstI-triggered FOXO3 nuclear translocation by phosphorylating MstI, promoting cell survival. PMID- 17726017 TI - Role of the Jak/STAT pathway in the regulation of interleukin-8 transcription by oxidized phospholipids in vitro and in atherosclerosis in vivo. AB - Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (Ox-PAPC) and its component phospholipid, 1-palmitoyl-2-epoxyisoprostane-sn-glycero-3 phosphorylcholine, induce endothelial cells (EC) to synthesize chemotactic factors, such as interleukin 8 (IL-8). Previously, we demonstrated a role for c Src kinase activation in Ox-PAPC-induced IL-8 transcription. In this study, we have examined the mechanism regulating IL-8 transcription by Ox-PAPC downstream of c-Src. Our findings demonstrate an important role for JAK2 in the regulation of IL-8 transcription by Ox-PAPC. Treatment of human aortic EC with Ox-PAPC and 1 palmitoyl-2-epoxyisoprostane-sn-glycero-3-phosphorylcholine induced a rapid yet sustained activation of JAK2; activation of JAK2 by Ox-PAPC was dependent on c Src kinase activity. Furthermore, pretreatment with selective JAK2 inhibitors significantly reduced Ox-PAPC-induced IL-8 transcription. In previous studies, we also demonstrated activation of STAT3 by Ox-PAPC. Here we provide evidence that STAT3 activation by Ox-PAPC is dependent on JAK2 activation and that STAT3 activation regulates IL-8 transcription by Ox-PAPC in human EC. Transfection with small interfering RNA against STAT3 significantly reduced Ox-PAPC-induced IL-8 transcription. Using chromatin immunoprecipitation assays, we demonstrated binding of activated STAT3 to the sequence flanking the consensus gamma interferon activation sequence (GAS) in the IL-8 promoter; site-directed mutagenesis of GAS inhibited IL-8 transcription by Ox-PAPC. Finally, these studies demonstrate a role for STAT3 activation in atherosclerosis in vivo. We found increased staining for activated STAT3 in the inflammatory regions of human atherosclerotic lesions and reduced fatty streak formation in EC-specific STAT3 knock-out mice on the atherogenic diet. Taken together, these data demonstrate an important role for the JAK2/STAT3 pathway in Ox-PAPC-induced IL-8 transcription in vitro and in atherosclerosis in vivo. PMID- 17726018 TI - Stimulation of actin polymerization by vacuoles via Cdc42p-dependent signaling. AB - We have previously shown that actin ligands inhibit the fusion of yeast vacuoles in vitro, which suggests that actin remodeling is a subreaction of membrane fusion. Here, we demonstrate the presence of vacuole-associated actin polymerization activity, and its dependence on Cdc42p and Vrp1p. Using a sensitive in vitro pyrene-actin polymerization assay, we found that vacuole membranes stimulated polymerization, and this activity increased when vacuoles were preincubated under conditions that support membrane fusion. Vacuoles purified from a VRP1-gene deletion strain showed reduced polymerization activity, which could be recovered when reconstituted with excess Vrp1p. Cdc42p regulates this activity because overexpression of dominant-negative Cdc42p significantly reduced vacuole-associated polymerization activity, while dominant-active Cdc42p increased activity. We also used size-exclusion chromatography to directly examine changes in yeast actin induced by vacuole fusion. This assay confirmed that actin undergoes polymerization in a process requiring ATP. To further confirm the need for actin polymerization during vacuole fusion, an actin polymerization-deficient mutant strain was examined. This strain showed in vivo defects in vacuole fusion, and actin purified from this strain inhibited in vitro vacuole fusion. Affinity isolation of vacuole-associated actin and in vitro binding assays revealed a polymerization-dependent interaction between actin and the SNARE Ykt6p. Our results suggest that actin polymerization is a subreaction of vacuole membrane fusion governed by Cdc42p signal transduction. PMID- 17726019 TI - S100B and S100A6 differentially modulate cell survival by interacting with distinct RAGE (receptor for advanced glycation end products) immunoglobulin domains. AB - S100 proteins are EF-hand calcium-binding proteins with various intracellular functions including cell proliferation, differentiation, migration, and apoptosis. Some S100 proteins are also secreted and exert extracellular paracrine and autocrine functions. Experimental results suggest that the receptor for advanced glycation end products (RAGE) plays important roles in mediating S100 protein-induced cellular signaling. Here we compared the interaction of two S100 proteins, S100B and S100A6, with RAGE by in vitro assay and in culture of human SH-SY5Y neuroblastoma cells. Our in vitro binding data showed that S100B and S100A6, although structurally very similar, interact with different RAGE extracellular domains. Our cell assay data demonstrated that S100B and S100A6 differentially modulate cell survival. At micromolar concentration, S100B increased cellular proliferation, whereas at the same concentration, S100A6 triggered apoptosis. Although both S100 proteins induced the formation of reactive oxygen species, S100B recruited phosphatidylinositol 3-kinase/AKT and NF kappaB, whereas S100A6 activated JNK. More importantly, we showed that S100B and S100A6 modulate cell survival in a RAGE-dependent manner; S100B specifically interacted with the RAGE V and C(1) domains and S100A6 specifically interacted with the C(1) and C(2) RAGE domains. Altogether these results highlight the complexity of S100/RAGE cellular signaling. PMID- 17726020 TI - A pathway separate from the central channel through the nuclear pore complex for inorganic ions and small macromolecules. AB - Nuclear pore complexes (NPCs) are supramolecular nanomachines that mediate the exchange of macromolecules and inorganic ions between the nucleus and the cytosol. Although there is no doubt that large cargo is transported through the centrally located channel, the route of ions and small molecules remains debatable. We thus tested the hypothesis that there are two separate pathways by imaging NPCs using atomic force microscopy, NPC electrical conductivity measurements, and macromolecule permeability assays. Our data indicate a spatial separation between the active transport of macromolecules through the central channel and the passive transport of ions and small macromolecules through the pore periphery. PMID- 17726021 TI - Succination of protein thiols during adipocyte maturation: a biomarker of mitochondrial stress. AB - Although obesity is a risk factor for development of type 2 diabetes and chemical modification of proteins by advanced glycoxidation and lipoxidation end products is implicated in the development of diabetic complications, little is known about the chemical modification of proteins in adipocytes or adipose tissue. In this study we show that S-(2-succinyl)cysteine (2SC), the product of chemical modification of proteins by the Krebs cycle intermediate, fumarate, is significantly increased during maturation of 3T3-L1 fibroblasts to adipocytes. Fumarate concentration increased > or =5-fold during adipogenesis in medium containing 30 mm glucose, producing a > or =10-fold increase in 2SC-proteins in adipocytes compared with undifferentiated fibroblasts grown in the same high glucose medium. The elevated glucose concentration in the medium during adipocyte maturation correlated with the increase in 2SC, whereas the concentration of the advanced glycoxidation and lipoxidation end products, N(epsilon) (carboxymethyl)lysine and N(epsilon)-(carboxyethyl)lysine, was unchanged under these conditions. Adipocyte proteins were separated by one- and two-dimensional electrophoresis and approximately 60 2SC-proteins were detected using an anti-2SC polyclonal antibody. Several of the prominent and well resolved proteins were identified by matrix-assisted laser desorption ionization time-of-flight/time-of flight mass spectrometry. These include cytoskeletal proteins, enzymes, heat shock and chaperone proteins, regulatory proteins, and a fatty acid-binding protein. We propose that the increase in fumarate and 2SC is the result of mitochondrial stress in the adipocyte during adipogenesis and that 2SC may be a useful biomarker of mitochondrial stress in obesity, insulin resistance, and diabetes. PMID- 17726023 TI - Cyclic nucleotide phosphodiesterase PDE1C1 in human cardiac myocytes. AB - Isoforms in the PDE1 family of cyclic nucleotide phosphodiesterases were recently found to comprise a significant portion of the cGMP-inhibited cAMP hydrolytic activity in human hearts. We examined the expression of PDE1 isoforms in human myocardium, characterized their catalytic activity, and quantified their contribution to cAMP hydrolytic and cGMP hydrolytic activity in subcellular fractions of this tissue. Western blotting with isoform-selective anti-PDE1 monoclonal antibodies showed PDE1C1 to be the principal isoform expressed in human myocardium. Immunohistochemical analysis showed that PDE1C1 is distributed along the Z-lines and M-lines of cardiac myocytes in a striated pattern that differs from that of the other major dual-specificity cyclic nucleotide phosphodiesterase in human myocardium, PDE3A. Most of the PDE1C1 activity was recovered in soluble fractions of human myocardium. It binds both cAMP and cGMP with K(m) values of approximately 1 microm and hydrolyzes both substrates with similar catalytic rates. PDE1C1 activity in subcellular fractions was quantified using a new PDE1-selective inhibitor, IC295. At substrate concentrations of 0.1 microm, PDE1C1 constitutes the great majority of cAMP hydrolytic and cGMP hydrolytic activity in soluble fractions and the majority of cGMP hydrolytic activity in microsomal fractions, whereas PDE3 constitutes the majority of cAMP hydrolytic activity in microsomal fractions. These results indicate that PDE1C1 is expressed at high levels in human cardiac myocytes with an intracellular distribution distinct from that of PDE3A and that it may have a role in the integration of cGMP-, cAMP- and Ca(2+)-mediated signaling in these cells. PMID- 17726022 TI - Mycobacterial cells have dual nickel-cobalt sensors: sequence relationships and metal sites of metal-responsive repressors are not congruent. AB - A novel ArsR-SmtB family transcriptional repressor, KmtR, has been characterized from mycobacteria. Mutants of Mycobacterium tuberculosis lacking kmtR show elevated expression of Rv2025c encoding a deduced CDF-family metal exporter. KmtR dependent repression of the cdf and kmtR operator-promoters was alleviated by nickel and cobalt in minimal medium. Electrophoretic mobility shift assays and fluorescence anisotropy show binding of purified KmtR to nucleotide sequences containing a region of dyad symmetry from the cdf and kmtR operator-promoters. Incubation of KmtR with cobalt inhibits DNA complex assembly and metal-protein binding was confirmed. KmtR is the second, to NmtR, characterized ArsR-SmtB sensor of nickel and cobalt from M. tuberculosis suggesting special significance for these ions in this pathogen. KmtR-dependent expression is elevated in complete medium with no increase in response to metals, whereas NmtR retains a response to nickel and cobalt under these conditions. KmtR has tighter affinities for nickel and cobalt than NmtR consistent with basal levels of these metals being sensed by KmtR but not NmtR in complete medium. More than a thousand genes encoding ArsR-SmtB-related proteins are listed in databases. KmtR has none of the previously defined metal-sensing sites. Substitution of His88, Glu101, His102, His110, or His111 with Gln generated KmtR variants that repress the cdf and kmtR operator-promoters even in elevated nickel and cobalt, revealing a new sensory site. Importantly, ArsR-SmtB sequence groupings do not correspond with the different sensory motifs revealing that only the latter should be used to predict metal sensing. PMID- 17726024 TI - The long form of the leptin receptor regulates STAT5 and ribosomal protein S6 via alternate mechanisms. AB - The action of leptin via the long form of its receptor (LepRb) is central to the control of body energy homeostasis and neuroendocrine function, but the mechanisms by which LepRb regulates intracellular signaling have remained incompletely understood. Here we demonstrate that leptin stimulates the phosphorylation of STAT5 and ribosomal protein S6 in the hypothalamic arcuate nucleus in mice. In cultured cells, we investigate the mechanisms by which leptin regulates each of these pathways. Our analysis reveals a dominant role for LepRb Tyr(1077) (which we demonstrate to be phosphorylated during receptor activation) and a secondary role for LepRb Tyr(1138) in the acute phosphorylation of STAT5a and STAT5b. Tyr(1138) and STAT3 attenuate STAT5-dependent transcription over the long-term, however. In contrast, Tyr(985) (the LepRb phosphorylation site required for ERK activation) mediates the phosphorylation of the ribosomal S6 kinase (RSK) and S6, as well as cap-dependent translation. Thus, these data demonstrate the phosphorylation of Tyr(1077) on LepRb during receptor activation, substantiate the hypothalamic regulation of STAT5 and S6 by leptin, and define the alternate LepRb signaling pathways that mediate each of these signals and their effects in cultured cells. Dissecting the contributions of these individual pathways to leptin action will be important for our ultimate understanding of the processes that regulate energy balance in vivo. PMID- 17726025 TI - Phenylalanine biosynthesis in Arabidopsis thaliana. Identification and characterization of arogenate dehydratases. AB - There is much uncertainty as to whether plants use arogenate, phenylpyruvate, or both as obligatory intermediates in Phe biosynthesis, an essential dietary amino acid for humans. This is because both prephenate and arogenate have been reported to undergo decarboxylative dehydration in plants via the action of either arogenate (ADT) or prephenate (PDT) dehydratases; however, neither enzyme(s) nor encoding gene(s) have been isolated and/or functionally characterized. An in silico data mining approach was thus undertaken to attempt to identify the dehydratase(s) involved in Phe formation in Arabidopsis, based on sequence similarity of PDT-like and ACT-like domains in bacteria. This data mining approach suggested that there are six PDT-like homologues in Arabidopsis, whose phylogenetic analyses separated them into three distinct subgroups. All six genes were cloned and subsequently established to be expressed in all tissues examined. Each was then expressed as a Nus fusion recombinant protein in Escherichia coli, with their substrate specificities measured in vitro. Three of the resulting recombinant proteins, encoded by ADT1 (At1g11790), ADT2 (At3g07630), and ADT6 (At1g08250), more efficiently utilized arogenate than prephenate, whereas the remaining three, ADT3 (At2g27820), ADT4 (At3g44720), and ADT5 (At5g22630) essentially only employed arogenate. ADT1, ADT2, and ADT6 had k(cat)/Km values of 1050, 7650, and 1560 M(-1) S(-1) for arogenate versus 38, 240, and 16 M(-1) S(-1) for prephenate, respectively. By contrast, the remaining three, ADT3, ADT4, and ADT5, had k(cat)/Km values of 1140, 490, and 620 M(-1) S(-1), with prephenate not serving as a substrate unless excess recombinant protein (>150 microg/assay) was used. All six genes, and their corresponding proteins, are thus provisionally classified as arogenate dehydratases and designated ADT1-ADT6. PMID- 17726026 TI - p66(ShcA) and oxidative stress modulate myogenic differentiation and skeletal muscle regeneration after hind limb ischemia. AB - Oxidative stress plays a pivotal role in ischemic injury, and p66(ShcA)ko mice exhibit both lower oxidative stress and decreased tissue damage following hind limb ischemia. Thus, it was investigated whether tissue regeneration following acute hind limb ischemia was altered in p66(ShcA)ko mice. Upon femoral artery dissection, muscle regeneration started earlier and was completed faster than in wild-type (WT) control. Moreover, faster regeneration was associated with decreased oxidative stress. Unlike ischemia, cardiotoxin injury induced similar skeletal muscle damage in both genotypes. However, p66(ShcA)ko mice regenerated faster, in agreement with the regenerative advantage upon ischemia. Since no difference between p66(ShcA)wt and knock-out (ko) mice was found in blood perfusion recovery after ischemia, satellite cells (SCs), a resident population of myogenic progenitors, were examined. Similar SCs numbers were present in WT and ko mice. However, in vitro cultured p66(ShcA)ko SCs displayed lower oxidative stress levels and higher proliferation rate and differentiated faster than WT. Furthermore, when exposed to sublethal H(2)O(2) doses, p66(ShcA)ko SCs were resistant to H(2)O(2)-induced inhibition of differentiation. Finally, myogenic conversion induced by MyoD overexpression was more efficient in p66(ShcA)ko fibroblasts compared with WT. The present work demonstrates that oxidative stress and p66(ShcA) play a crucial role in the regenerative pathways activated by acute ischemia. PMID- 17726027 TI - Transmembrane segment IV contributes a functionally important interface for oligomerization of the Class II G protein-coupled secretin receptor. AB - Oligomerization of the Class II G protein-coupled secretin receptor has been reported, but the molecular basis for this and its functional significance have not been determined. In the current work, we have examined the possible contribution of each of the transmembrane (TM) segments of this receptor to its homo-oligomerization, using the method of competitive disruption screening for inhibition of receptor bioluminescence resonance energy transfer signal. TM IV was the only segment that was found to disrupt receptor bioluminescence resonance energy transfer. Evaluation of predicted interhelical and lipid-exposed faces of this TM segment demonstrated that its lipid-exposed face represented the determinant for oligomerization. This was further confirmed by mutagenesis of the intact secretin receptor. Morphological FRET was utilized to demonstrate that secretin receptor oligomerization occurred at the cell surface and that this oligomerization was disrupted by mutating Gly(243) and Ile(247), key residues within the lipid-exposed face of TM IV. Although disruption of the receptor oligomerization interface had no effect on secretin binding parameters, it reduced the ability of secretin to stimulate intracellular cAMP. This supports a clear functional effect of oligomerization of this receptor. Such an effect might be particularly relevant to clinical situations in which this receptor is overexpressed, such as in certain neoplasms. PMID- 17726028 TI - JAK2 tyrosine kinase phosphorylates PAK1 and regulates PAK1 activity and functions. AB - The serine-threonine kinase PAK1 is activated by small GTPase-dependent and independent mechanisms and promotes cell survival. However, the role of tyrosyl phosphorylation in the regulation of PAK1 function is poorly understood. In this study, we have shown that the prolactin-activated tyrosine kinase JAK2 phosphorylates PAK1 in vivo. Wild type, but not kinase-dead, JAK2 directly phosphorylates PAK1 in cells and in an in vitro kinase assay. PAK1 tyrosines 153, 201, and 285 were identified as sites of JAK2 tyrosyl phosphorylation by mass spectrometry and two-dimensional peptide mapping. Mutation of PAK1 tyrosines 153, 201, and 285 to phenylalanines individually or in combination implicated these PAK1 tyrosines in the regulation of PAK1 kinase activity. Tyrosyl phosphorylation by JAK2 significantly increases PAK1 kinase activity, whereas similar phosphorylation of the PAK1 Y153F,Y201F,Y285F mutant has no effect on PAK1 activity. Tyrosyl phosphorylation of wild type PAK1 decreases apoptosis induced by serum deprivation and staurosporine treatment and increases cell motility. In contrast, these parameters are unaltered in the PAK1 Y153F,Y201F,Y285F mutant. Our findings indicate that JAK2 phosphorylates PAK1 at these specific tyrosines and that this phosphorylation plays an important role in cell survival and motility. PMID- 17726029 TI - Further evidence for two functional forms of prothrombinase each specific for either of the two prothrombin activation cleavages. AB - Previous work showed that prothrombin derivatives cleavable only at Arg-320 (rMZ) or Arg-271 (rP2) are partial, rather than competitive, inhibitors of prothrombin activation by prothrombinase. A "ping-pong"-like model, which posits two equilibrating forms of prothrombinase, explained the inhibition pattern. The present studies were undertaken to further investigate this putative mechanism. Two models were developed, one allowing for one form of the enzyme and the other allowing for two forms. Both models also allowed channeling and ratcheting. The models were fit to full time courses of prothrombin, meizothrombin, prethrombin 2, and the B-chain. In the absence of ratcheting and channeling, neither model fits the data. In their presence, however, both models fit very well, and thus they could not be distinguished. Therefore, inhibition of rMZ activation by rP2 was studied. Inhibition was partial and the two-form model fit the data with randomly distributed residuals, whereas the one-form model did not. Initial rates of fluorescein-labeled prothrombin cleavage in the presence of various prothrombin derivatives reported by Brufatto and Nesheim (Brufatto, N., and Nesheim, M. E. (2003) J. Biol. Chem. 278, 6755-6764) were also analyzed using the two models. The two-form model fit the partial inhibition data well, whereas the one-form model did not. In addition, prothrombin at varying concentrations was activated, and subsequently, the initial rates were plotted with respect to the initial prothrombin concentration. When compared with the expected initial rates as determined by the simulation of the models, the two-form model fit the observed rates better than the one-form model. The results obtained here further support the existence of two functional forms of prothrombinase. PMID- 17726030 TI - Ubiquitination of mammalian Pex5p, the peroxisomal import receptor. AB - Protein translocation across the peroxisomal membrane requires the concerted action of numerous peroxins. One central component of this machinery is Pex5p, the cycling receptor for matrix proteins. Pex5p recognizes newly synthesized proteins in the cytosol and promotes their translocation across the peroxisomal membrane. After this translocation step, Pex5p is recycled back into the cytosol to start a new protein transport cycle. Here, we show that mammalian Pex5p is ubiquitinated at the peroxisomal membrane. Two different types of ubiquitination were detected, one of which is thiol-sensitive, involves Cys(11) of Pex5p, and is necessary for the export of the receptor back into the cytosol. Together with mechanistic data recently described for yeast Pex5p, these findings provide strong evidence for the existence of Pex4p- and Pex22p-like proteins in mammals. PMID- 17726031 TI - An endoplasmic reticulum transmembrane prolyl 4-hydroxylase is induced by hypoxia and acts on hypoxia-inducible factor alpha. AB - Prolyl 4-hydroxylases (P4Hs) act on collagens (C-P4Hs) and the oxygen-dependent degradation domains (ODDDs) of hypoxia-inducible factor alpha subunits (HIF-P4Hs) leading to degradation of the latter. We report data on a human P4H possessing a transmembrane domain (P4H-TM). Its gene is also found in zebrafish but not in flies and nematodes. Its sequence more closely resembles those of the C-P4Hs than the HIF-P4Hs, but it lacks the peptide substrate-binding domain of the C-P4Hs. P4H-TM levels in cultured cells are increased by hypoxia, and P4H-TM is N glycosylated and is located in endoplasmic reticulum membranes with its catalytic site inside the lumen, a location differing from those of the HIF-P4Hs. Despite this, P4H-TM overexpression in cultured neuroblastoma cells reduced HIF-alpha ODDD reporter construct levels, and its small interfering RNA increased HIF 1alpha protein level, in the same way as those of HIF-P4Hs. Furthermore, recombinant P4H-TM hydroxylated the two critical prolines in HIF-1alpha ODDD in vitro, with a preference for the C-terminal proline, whereas it did not hydroxylate any prolines in recombinant type I procollagen chains. PMID- 17726032 TI - A review of STD/HIV preventive interventions for adolescents: sustaining effects using an ecological approach. AB - OBJECTIVE: Behavioral intervention programs to reduce adolescent sexual risk behaviors have shown statistically significant reductions in the short-term; however, longer-term follow-up has demonstrated that effects diminish. One criticism has been the reliance on individual-level models. We review the research that has shaped this narrow perspective and propose that a broader, ecological perspective is needed to amplify and extend the efficacy of sexual risk reduction interventions. METHODS: We summarize adolescent sexual risk research and outline intervention research that is suggestive of an ecological perspective. Examples from the published literature that have investigated antecedents or conceptualized preventive interventions using a multilevel approach are provided. RESULTS: Adolescents are exposed to diverse sources of influence transecting different levels of causation. To adequately prevent, reduce, and maintain the likelihood of adolescents' adopting sexual risk behaviors, intervention programs should be designed to address these myriad levels of causation. This approach has been implemented in Brazil and was shown to be effective. CONCLUSION: Research should cross manifold levels of causation so that programs will be more effective at promoting adolescents' adoption and maintenance of STD/HIV preventive behaviors. PMID- 17726033 TI - COX-2 inhibitor. PMID- 17726034 TI - Severe disabling tendinopathy caused by anastrazole. PMID- 17726035 TI - Successful treatment of refractory lupus-associated haemophagocytic lymphohistiocytosis with infliximab. PMID- 17726036 TI - The expression of SOCS is altered in rheumatoid arthritis. AB - OBJECTIVES: Cytokines play a key pathogenic role in rheumatoid arthritis (RA). Several cytokines signal through the JAK-STAT pathway, which is negatively regulated by the suppressors of cytokine signalling (SOCS) proteins. Since SOCS protein levels can profoundly modulate cellular responses to cytokines, we have investigated their expression in chronic RA. METHODS: The levels of SOCS1-3 and CIS1 mRNA in peripheral blood (PB) and synovial fluid (SF) mononuclear cells (MCs), purified T cells and monocytes from RA patients and healthy volunteers were studied using quantitative reverse transcriptase polymerase chain reaction (RT-PCR). SOCS mRNA and protein expression in synovial tissues were examined by RT-PCR and immunohistochemistry. RESULTS: The levels of SOCS1 and SOCS3 were significantly increased in PBMCs from RA patients when compared with healthy volunteers. These differences were mainly due to up-regulation of SOCS1 in PB T cells and of SOCS3 in PB monocytes. In addition, SOCS2 was up-regulated in PB T cells. Interestingly, SF T cells expressed lower and SF macrophages higher levels of SOCS molecules than their PB counterparts. Similarly, while a significant portion of macrophages in synovial tissues expressed SOCS1 and SOCS3 proteins, the majority of T cells remained SOCS negative. Finally, SOCS1 was up-regulated in the synovial membranes from patients with RA when compared with osteoarthritis. CONCLUSIONS: SOCS expression levels are profoundly altered in RA, and the profile of SOCS expression is dependent on both the cell type as well as the cellular compartment. PMID- 17726037 TI - Intervention targeted at nurses to improve venous thromboprophylaxis. AB - OBJECTIVE: To assess the effectiveness of an intervention targeting both physicians and nurses vs. physicians only in improving venous thromboprophylaxis for older patients. DESIGN: Cluster randomized trial. SETTING: Fifty hospital based post-acute care departments in France. PARTICIPANTS: Patients aged 65 years or older. INTERVENTION: A multifaceted intervention to implement a clinical practice guideline addressing venous thromboprophylaxis. MAIN OUTCOME MEASURES: The effectiveness outcomes were elastic stocking use, ambulation or mobilization under the supervision of a physical therapist and anticoagulant-based prophylaxis. Patient outcomes included deep vein thrombosis and anticoagulant related adverse events. RESULTS: One department allocated to the intervention targeted at physicians only and seven departments allocated to the intervention targeted at both physicians and nurses dropped out of the study. Compared with the intervention targeted at physicians only (n = 497 patients), the intervention targeted at both physicians and nurses (n = 315 patients) was associated with a higher rate of mobilization (62 vs. 37%, P < 0.001) and comparable levels of elastic stocking (32 vs. 39%, P = 0.74) and anticoagulant (55 vs. 48%, P = 0.36) use. The rates of deep vein thrombosis (15 vs. 13%, P = 0.50), bleeding (1 vs. 1%, P = 0.99) and thrombocytopaenia (0 vs. 0.2%, P = 0.99) did not differ between the two groups. CONCLUSIONS: A multifaceted intervention targeting nurses in addition to physicians can increase the frequency of mobilization of older patients to prevent venous thromboembolism but does not alter the use of elastic stockings and anticoagulant. A differential drop-out of departments might have contributed to creating imbalances in baseline characteristics and outcomes in this study. PMID- 17726038 TI - Cohort profile: The Adventist Health Study-2 (AHS-2). PMID- 17726039 TI - The impact of pesticide regulations on suicide in Sri Lanka. AB - BACKGROUND: Between 1950 and 1995 suicide rates in Sri Lanka increased 8-fold to a peak of 47 per 100,000 in 1995. By 2005, rates had halved. We investigated whether Sri Lanka's regulatory controls on the import and sale of pesticides that are particularly toxic to humans were responsible for these changes in the incidence of suicide. METHODS: Ecological analysis using graphical and descriptive approaches to identify time trends in suicide and risk factors for suicide in Sri Lanka, 1975-2005. RESULTS: Restrictions on the import and sales of WHO Class I toxicity pesticides in 1995 and endosulfan in 1998, coincided with reductions in suicide in both men and women of all ages. 19,769 fewer suicides occurred in 1996-2005 as compared with 1986-95. Secular trends in unemployment, alcohol misuse, divorce, pesticide use and the years associated with Sri Lanka's Civil war did not appear to be associated with these declines. CONCLUSION: These data indicate that in countries where pesticides are commonly used in acts of self-poisoning, import controls on the most toxic pesticides may have a favourable impact on suicide. In Asia, there are an estimated 300,000 deaths from pesticide self-poisoning annually. National and international policies restricting the sale of pesticides that are most toxic to humans may have a major impact on suicides in the region. PMID- 17726040 TI - Estimating interaction on an additive scale between continuous determinants in a logistic regression model. AB - BACKGROUND: To determine the presence of interaction in epidemiologic research, typically a product term is added to the regression model. In linear regression, the regression coefficient of the product term reflects interaction as departure from additivity. However, in logistic regression it refers to interaction as departure from multiplicativity. Rothman has argued that interaction estimated as departure from additivity better reflects biologic interaction. So far, literature on estimating interaction on an additive scale using logistic regression only focused on dichotomous determinants. The objective of the present study was to provide the methods to estimate interaction between continuous determinants and to illustrate these methods with a clinical example. METHODS: and results From the existing literature we derived the formulas to quantify interaction as departure from additivity between one continuous and one dichotomous determinant and between two continuous determinants using logistic regression. Bootstrapping was used to calculate the corresponding confidence intervals. To illustrate the theory with an empirical example, data from the Utrecht Health Project were used, with age and body mass index as risk factors for elevated diastolic blood pressure. CONCLUSIONS: The methods and formulas presented in this article are intended to assist epidemiologists to calculate interaction on an additive scale between two variables on a certain outcome. The proposed methods are included in a spreadsheet which is freely available at: http://www.juliuscenter.nl/additive-interaction.xls. PMID- 17726042 TI - Guidelines for cardiac pacing and cardiac resynchronization therapy: The Task Force for Cardiac Pacing and Cardiac Resynchronization Therapy of the European Society of Cardiology. Developed in collaboration with the European Heart Rhythm Association. PMID- 17726043 TI - Guidelines for cardiac pacing and cardiac resynchronization therapy. The Task Force for Cardiac Pacing and Cardiac Resynchronization Therapy of the European Society of Cardiology. Developed in collaboration with the European Heart Rhythm Association. PMID- 17726041 TI - European guidelines on cardiovascular disease prevention in clinical practice: executive summary: Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (Constituted by representatives of nine societies and by invited experts). PMID- 17726044 TI - Stabilization of SMAR1 mRNA by PGA2 involves a stem loop structure in the 5' UTR. AB - Prostaglandins are anticancer agents known to inhibit tumor cell proliferation both in vitro and in vivo by affecting the mRNA stability. Here we report that a MAR-binding protein SMAR1 is a target of Prostaglandin A2 (PGA2) induced growth arrest. We identify a regulatory mechanism leading to stabilization of SMAR1 transcript. Our results show that a minor stem and loop structure present in the 5' UTR of SMAR1 (1-UTR) is critical for nucleoprotein complex formation that leads to SMAR1 stabilization in response to PGA2. This results in an increased SMAR1 transcript and altered protein levels, that in turn causes downregulation of Cyclin D1 gene, essential for G1/S phase transition. We also provide evidence for the presence of a variant 5' UTR SMAR1 (17-UTR) in breast cancer-derived cell lines. This form lacks the minor stem and loop structure required for mRNA stabilization in response to PGA2. As a consequence of this, there is a low level of endogenous tumor suppressor protein SMAR1 in breast cancer-derived cell lines. Our studies provide a mechanistic insight into the regulation of tumor suppressor protein SMAR1 by a cancer therapeutic PGA2, that leads to repression of Cyclin D1 gene. PMID- 17726045 TI - In vitro and in silico analysis reveals an efficient algorithm to predict the splicing consequences of mutations at the 5' splice sites. AB - We have found that two previously reported exonic mutations in the PINK1 and PARK7 genes affect pre-mRNA splicing. To develop an algorithm to predict underestimated splicing consequences of exonic mutations at the 5' splice site, we constructed and analyzed 31 minigenes carrying exonic splicing mutations and their derivatives. We also examined 189,249 U2-dependent 5' splice sites of the entire human genome and found that a new variable, the SD-Score, which represents a common logarithm of the frequency of a specific 5' splice site, efficiently predicts the splicing consequences of these minigenes. We also employed the information contents (R(i)) to improve the prediction accuracy. We validated our algorithm by analyzing 32 additional minigenes as well as 179 previously reported splicing mutations. The SD-Score algorithm predicted aberrant splicings in 198 of 204 sites (sensitivity = 97.1%) and normal splicings in 36 of 38 sites (specificity = 94.7%). Simulation of all possible exonic mutations at positions 3, -2 and -1 of the 189 249 sites predicts that 37.8, 88.8 and 96.8% of these mutations would affect pre-mRNA splicing, respectively. We propose that the SD Score algorithm is a practical tool to predict splicing consequences of mutations affecting the 5' splice site. PMID- 17726046 TI - siRNA-dependent and -independent post-transcriptional cosuppression of the LTR retrotransposon MAGGY in the phytopathogenic fungus Magnaporthe oryzae. AB - The LTR-retrotransposon MAGGY was introduced into naive genomes of Magnaporthe oryzae with different genetic backgrounds (wild-type, and MoDcl1 [mdl1] and MoDcl2 [mdl2] dicer mutants). The MoDcl2 mutants deficient in MAGGY siRNA biogenesis generally showed greater MAGGY mRNA accumulation and more rapid increase in MAGGY copy number than did the wild-type and MoDcl1 mutants exhibiting normal MAGGY siRNA accumulation, indicating that RNA silencing functioned as an effective defense against the invading element. Interestingly, however, regardless of genetic background, the rate of MAGGY transposition drastically decreased as its copy number in the genome increased. Notably, in the MoDcl2 mutant, copy-number-dependent MAGGY suppression occurred without a reduction in its mRNA accumulation, and therefore by a silencing mechanism distinct from both transcriptional gene silencing and siRNA-mediated RNA silencing. This might imply that some mechanism possibly similar to post transcriptional cosuppression of Ty1 retrotransposition in Saccharomyces cerevisiae, which operates regardless of the abundance of target transcript and independent of RNA silencing, would also function in M. oryzae that possesses the RNA silencing machinery. PMID- 17726047 TI - Poly(A) binding protein, C-terminally truncated by the hepatitis A virus proteinase 3C, inhibits viral translation. AB - Proteolytic cleavage of translation initiation factors is a means to interfere with mRNA circularization and to induce translation arrest during picornaviral replication or apoptosis. It was shown that the regulated cleavages of eukaryotic initiation factor (eIF) 4G and poly(A)-binding protein (PABP) by viral proteinases correlated with early and late arrest of host cap-dependent and viral internal ribosome entry site (IRES)-dependent translation, respectively. Here we show that in contrast to coxsackievirus, eIF4G is not a substrate of proteinase 3C of hepatitis A virus (HAV 3C(pro)). However, PABP is cleaved by HAV 3C(pro) in vitro and in vivo, separating the N-terminal RNA-binding domain (NTD) of PABP from the C-terminal protein-interaction domain. In vitro, NTD has a dominant negative effect on HAV IRES-dependent translation and an enhanced binding affinity to the RNA structural element pY1 in the 5' nontranslated region of the HAV RNA that is essential for viral genome replication. The results point to a regulatory role of PABP cleavage in RNA template switching of viral translation to RNA synthesis. PMID- 17726048 TI - Efficient expression of gene variants that harbour AGA codons next to the initiation codon. AB - In an effort to improve the knowledge about the rules which direct the effect of the early ORF sequences on translation efficiency, we have analyzed the effect of pairs of the six arginine codons at the second and third positions on the expression of lacZ variants. Whereas the pairs of identical AGA or AGG codons were favorable for the gene expression, identical pairs of each of the four CGN codons were very inefficient. This result was unexpected because tandems of AGA or AGG codons located in more internal gene positions provoke deficient expression whilst internally located CGU and CGC are the most abundant and efficiently translated arginine codons. The mixed combinations of AGA and each of the CGN codons usually resulted in efficient rates of lacZ expression independently of the peptidyl-tRNA propensity to dissociate from the ribosome. Thus, the variant harboring the pair of AGA codons was expressed as efficiently as the variant carrying a pair of AAA codons in the same positions, a configuration reported as one of the most common and efficient for gene expression. We explain these results assuming that the presence of adenines in these early positions enhance gene expression. As expected, specific mRNA levels correlated with the intensity of lacZ expression for each variant. However, the induction of lacZ AGA AGA gene in pth cells accumulated peptidyl-tRNA(Arg4) as well as a short 5'-proximal lacZ mRNA fragment suggesting ribosome stalling due to depletion of aminoacylated-tRNA(Arg4). PMID- 17726049 TI - The p300/CBP-associated factor (PCAF) is a cofactor of ATF4 for amino acid regulated transcription of CHOP. AB - When an essential amino acid is limited, a signaling cascade is triggered that leads to increased translation of the 'master regulator', activating transcription factor 4 (ATF4), and resulting in the induction of specific target genes. Binding of ATF4 to the amino acid response element (AARE) is an essential step in the transcriptional activation of CHOP (a CCAAT/enhancer-binding protein related gene) by amino acid deprivation. We set out to identify proteins that interact with ATF4 and that play a role in the transcriptional activation of CHOP. Using a tandem affinity purification (TAP) tag approach, we identified p300/CBP-associated factor (PCAF) as a novel interaction partner of ATF4 in leucine-starved cells. We show that the N-terminal region of ATF4 is required for a direct interaction with PCAF and demonstrate that PCAF is involved in the full transcriptional response of CHOP by amino acid starvation. Chromatin immunoprecipitation analysis revealed that PCAF is engaged on the CHOP AARE in response to amino acid starvation and that ATF4 is essential for its recruitment. We also show that PCAF stimulates ATF4-driven transcription via its histone acetyltransferase domain. Thus PCAF acts as a coactivator of ATF4 and is involved in the enhancement of CHOP transcription following amino acid starvation. PMID- 17726050 TI - Tissue-dependent paired expression of miRNAs. AB - It is believed that depending on the thermodynamic stability of the 5'-strand and the 3'-strand in the stem-loop structure of a precursor microRNA (pre-miRNA), cells preferentially select the less stable one (called the miRNA or guide strand) and destroy the other one (called the miRNA* or passenger strand). However, our expression profiling analyses revealed that both strands could be co accumulated as miRNA pairs in some tissues while being subjected to strand selection in other tissues. Our target prediction and validation assays demonstrated that both strands of a miRNA pair could target equal numbers of genes and that both were able to suppress the expression of their target genes. Our finding not only suggests that the numbers of miRNAs and their targets are much greater than what we previously thought, but also implies that novel mechanisms are involved in the tissue-dependent miRNA biogenesis and target selection process. PMID- 17726051 TI - A rapid high-throughput method for the detection and quantification of RNA editing based on high-resolution melting of amplicons. AB - We describe a rapid, high-throughput method to scan for new RNA editing sites. This method is adapted from high-resolution melting (HRM) analysis of amplicons, a technique used in clinical research to detect mutations in genomes. The assay was validated by the discovery of six new editing sites in different chloroplast transcripts of Arabidopsis thaliana. A screen of a collection of mutants uncovered a mutant defective for editing of one of the newly discovered sites. We successfully adapted the technique to quantify editing of partially edited sites in different individuals or different tissues. This new method will be easily applicable to RNA from any organism and should greatly accelerate the study of the role of RNA editing in physiological processes as diverse as plant development or human health. PMID- 17726052 TI - Human tryptophanyl-tRNA synthetase is switched to a tRNA-dependent mode for tryptophan activation by mutations at V85 and I311. AB - For most aminoacyl-tRNA synthetases (aaRS), their cognate tRNA is not obligatory to catalyze amino acid activation, with the exception of four class I (aaRS): arginyl-tRNA synthetase, glutamyl-tRNA synthetase, glutaminyl-tRNA synthetase and class I lysyl-tRNA synthetase. Furthermore, for arginyl-, glutamyl- and glutaminyl-tRNA synthetase, the integrated 3' end of the tRNA is necessary to activate the ATP-PPi exchange reaction. Tryptophanyl-tRNA synthetase is a class I aaRS that catalyzes tryptophan activation in the absence of its cognate tRNA. Here we describe mutations located at the appended beta1-beta2 hairpin and the AIDQ sequence of human tryptophanyl-tRNA synthetase that switch this enzyme to a tRNA-dependent mode in the tryptophan activation step. For some mutant enzymes, ATP-PPi exchange activity was completely lacking in the absence of tRNA(Trp), which could be partially rescued by adding tRNA(Trp), even if it had been oxidized by sodium periodate. Therefore, these mutant enzymes have strong similarity to arginyl-tRNA synthetase, glutaminyl-tRNA synthetase and glutamyl tRNA synthetase in their mode of amino acid activation. The results suggest that an aaRS that does not normally require tRNA for amino acid activation can be switched to a tRNA-dependent mode. PMID- 17726054 TI - Molecular basis of Diamond-Blackfan anemia: structure and function analysis of RPS19. AB - Diamond-Blackfan anemia (DBA) is a rare congenital disease linked to mutations in the ribosomal protein genes rps19, rps24 and rps17. It belongs to the emerging class of ribosomal disorders. To understand the impact of DBA mutations on RPS19 function, we have solved the crystal structure of RPS19 from Pyrococcus abyssi. The protein forms a five alpha-helix bundle organized around a central amphipathic alpha-helix, which corresponds to the DBA mutation hot spot. From the structure, we classify DBA mutations relative to their respective impact on protein folding (class I) or on surface properties (class II). Class II mutations cluster into two conserved basic patches. In vivo analysis in yeast demonstrates an essential role for class II residues in the incorporation into pre-40S ribosomal particles. This data indicate that missense mutations in DBA primarily affect the capacity of the protein to be incorporated into pre-ribosomes, thus blocking maturation of the pre-40S particles. PMID- 17726053 TI - Homing endonuclease mediated gene targeting in Anopheles gambiae cells and embryos. AB - Homing endonuclease genes (HEGs) are 'selfish' genetic elements that combine the capability to selectively disrupt specific gene sequences with the ability to rapidly spread from a few individuals to an entire population through homologous recombination repair events. Because of these properties, HEGs are regarded as promising candidates to transfer genetic modifications from engineered laboratory mosquitoes to wild-type populations including Anopheles gambiae the vector of human malaria. Here we show that I-SceI and I-PpoI homing endonucleases cleave their recognition sites with high efficiency in A. gambiae cells and embryos and we demonstrate HEG-induced homologous and non-homologous repair events in a variety of functional assays. We also propose a gene drive system for mosquitoes that is based on our finding that I-PpoI cuts genomic rDNA located on the X chromosome in A. gambiae, which could be used to selectively incapacitate X carrying spermatozoa thereby imposing a severe male-biased sex ratio. PMID- 17726055 TI - Efficacy assessment of SNP sets for genome-wide disease association studies. AB - The power of a genome-wide disease association study depends critically upon the properties of the marker set used, particularly the number and physical spacing of markers, and the level of inter-marker association due to linkage disequilibrium. Extending our previously devised theoretical framework for the entropy-based selection of genetic markers, we have developed a local measure of the efficacy of a marker set, relative to including a maximally polymorphic single nucleotide polymorphism (SNP) at the map position of interest. Using this quantitative criterion, we evaluated five currently available SNP sets, namely Affymetrix 100K and 500K, and Illumina 100K, 300K and 550K in the CEU, YRI and JPT + CHB HapMap populations. At 50% relative efficacy, the commercial marker sets cover between 19 and 68% of the human genome, depending upon the population under study. An optimal technology-independent 500K marker set constructed from HapMap for Caucasians, in contrast, would achieve 73% coverage at the same relative efficacy. PMID- 17726056 TI - The checkpoint Saccharomyces cerevisiae Rad9 protein contains a tandem tudor domain that recognizes DNA. AB - DNA damage checkpoints are signal transduction pathways that are activated after genotoxic insults to protect genomic integrity. At the site of DNA damage, 'mediator' proteins are in charge of recruiting 'signal transducers' to molecules 'sensing' the damage. Budding yeast Rad9, fission yeast Crb2 and metazoan 53BP1 are presented as mediators involved in the activation of checkpoint kinases. Here we show that, despite low sequence conservation, Rad9 exhibits a tandem tudor domain structurally close to those found in human/mouse 53BP1 and fission yeast Crb2. Moreover, this region is important for the resistance of Saccharomyces cerevisiae to different genotoxic stresses. It does not mediate direct binding to a histone H3 peptide dimethylated on K79, nor to a histone H4 peptide dimethylated on lysine 20, as was demonstrated for 53BP1. However, the tandem tudor region of Rad9 directly interacts with single-stranded DNA and double stranded DNAs of various lengths and sequences through a positively charged region absent from 53BP1 and Crb2 but present in several yeast Rad9 homologs. Our results argue that the tandem tudor domains of Rad9, Crb2 and 53BP1 mediate chromatin binding next to double-strand breaks. However, their modes of chromatin recognition are different, suggesting that the corresponding interactions are differently regulated. PMID- 17726057 TI - Improved silencing properties using small internally segmented interfering RNAs. AB - RNA interference is mediated by small interfering RNAs (siRNAs) that upon incorporation into the RNA-induced silencing complex (RISC) can target complementary mRNA for degradation. Standard siRNA design usually feature a 19-27 base pair contiguous double-stranded region that is believed to be important for RISC incorporation. Here, we describe a novel siRNA design composed of an intact antisense strand complemented with two shorter 10-12 nt sense strands. This three stranded construct, termed small internally segmented interfering RNA (sisiRNA), is highly functional demonstrating that an intact sense strand is not a prerequisite for RNA interference. Moreover, when using the sisiRNA design only the antisense strand is functional in activated RISC thereby completely eliminating unintended mRNA targeting by the sense strand. Interestingly, the sisiRNA design supports the function of chemically modified antisense strands, which are non-functional within the context of standard siRNA designs. This suggests that the sisiRNA design has a clear potential of improving the pharmacokinetic properties of siRNA in vivo. PMID- 17726058 TI - The U1 snRNP-associated factor Luc7p affects 5' splice site selection in yeast and human. AB - yLuc7p is an essential subunit of the yeast U1 snRNP and contains two putative zinc fingers. Using RNA-protein cross-linking and directed site-specific proteolysis (DSSP), we have established that the N-terminal zinc finger of yLuc7p contacts the pre-mRNA in the 5' exon in a region close to the cap. Modifying the pre-mRNA sequence in the region contacted by yLuc7p affects splicing in a yLuc7p dependent manner indicating that yLuc7p stabilizes U1 snRNP-pre-mRNA interaction, thus reminding of the mode of action of another U1 snRNP component, Nam8p. Database searches identified three putative human yLuc7p homologs (hLuc7A, hLuc7B1 and hLuc7B2). These proteins have an extended C-terminal tail rich in RS and RE residues, a feature characteristic of splicing factors. Consistent with a role in pre-mRNA splicing, hLuc7A localizes in the nucleus and antibodies raised against hLuc7A specifically co-precipitate U1 snRNA from human cell extracts. Interestingly, hLuc7A overexpression affects splicing of a reporter in vivo. Taken together, our data suggest that the formation of a wide network of protein RNA interactions around the 5' splice site by U1 snRNP-associated factors contributes to alternative splicing regulation. PMID- 17726060 TI - P-STAT1 mediates higher-order chromatin remodelling of the human MHC in response to IFNgamma. AB - Transcriptional activation of the major histocompatibility complex (MHC) by IFNgamma is a key step in cell-mediated immunity. At an early stage of IFNgamma induction, chromatin carrying the entire MHC locus loops out from the chromosome 6 territory. We show here that JAK/STAT signalling triggers this higher-order chromatin remodelling and the entire MHC locus becomes decondensed prior to transcriptional activation of the classical HLA class II genes. A single point mutation of STAT1 that prevents phosphorylation is sufficient to abolish chromatin remodelling, thus establishing a direct link between the JAK/STAT signalling pathway and human chromatin architecture. The onset of chromatin remodelling corresponds with the binding of activated STAT1 and the chromatin remodelling enzyme BRG1 at specific sites within the MHC, and is followed by RNA polymerase recruitment and histone hyperacetylation. We propose that the higher order chromatin remodelling of the MHC locus is an essential step to generate a transcriptionally permissive chromatin environment for subsequent activation of classical HLA genes. PMID- 17726059 TI - Cdc42 acts downstream of Bazooka to regulate neuroblast polarity through Par-6 aPKC. AB - Cdc42 recruits Par-6-aPKC to establish cell polarity from worms to mammals. Although Cdc42 is reported to have no function in Drosophila neuroblasts, a model for cell polarity and asymmetric cell division, we show that Cdc42 colocalizes with Par-6-aPKC at the apical cortex in a Bazooka-dependent manner, and is required for Par-6-aPKC localization. Loss of Cdc42 disrupts neuroblast polarity: cdc42 mutant neuroblasts have cytoplasmic Par-6-aPKC, and this phenotype is mimicked by neuroblast-specific expression of a dominant-negative Cdc42 protein or a Par-6 protein that lacks Cdc42-binding ability. Conversely, expression of constitutively active Cdc42 leads to ectopic Par-6-aPKC localization and corresponding cell polarity defects. Bazooka remains apically enriched in cdc42 mutants. Robust Cdc42 localization requires Par-6, indicating the presence of feedback in this pathway. In addition to regulating Par-6-aPKC localization, Cdc42 increases aPKC activity by relieving Par-6 inhibition. We conclude that Cdc42 regulates aPKC localization and activity downstream of Bazooka, thereby directing neuroblast cell polarity and asymmetric cell division. PMID- 17726061 TI - Phosphorylation of synapsin domain A is required for post-tetanic potentiation. AB - Post-tetanic potentiation (PTP) is a form of homosynaptic plasticity important for information processing and short-term memory in the nervous system. The synapsins, a family of synaptic vesicle (SV)-associated phosphoproteins, have been implicated in PTP. Although several synapsin functions are known to be regulated by phosphorylation by multiple protein kinases, the role of individual phosphorylation sites in synaptic plasticity is poorly understood. All the synapsins share a phosphorylation site in the N-terminal domain A (site 1) that regulates neurite elongation and SV mobilization. Here, we have examined the role of phosphorylation of synapsin domain A in PTP and other forms of short-term synaptic enhancement (STE) at synapses between cultured Helix pomatia neurons. To this aim, we cloned H. pomatia synapsin (helSyn) and overexpressed GFP-tagged wild-type helSyn or site-1-mutant helSyn mutated in the presynaptic compartment of C1-B2 synapses. We found that PTP at these synapses depends both on Ca2+/calmodulin-dependent and cAMP-dependent protein kinases, and that overexpression of the non-phosphorylatable helSyn mutant, but not wild-type helSyn, specifically impairs PTP, while not altering facilitation and augmentation. Our findings show that phosphorylation of site 1 has a prominent role in the expression of PTP, thus defining a novel role for phosphorylation of synapsin domain A in short-term homosynaptic plasticity. PMID- 17726062 TI - Antagonistic action of harpin proteins: HrpWea from Erwinia amylovora suppresses HrpNea-induced cell death in Arabidopsis thaliana. AB - Harpins are proteins secreted by the type-three secretion system of phytopathogenic bacteria. They are known to induce a hypersensitive response (HR) in non-host plant leaf tissue. Erwinia amylovora, the fire blight pathogen of pear and apple trees, secretes two different harpins, HrpNea and HrpWea. In the present study, we showed that an Erwinia amylovora hrpWea mutant induces stronger electrolyte leakages in Arabidopsis thaliana foliar disks than the wild-type strain, thus suggesting that HrpWea could function as a HR negative modulator. We confirmed this result by using purified HrpWea and HrpNea. HrpWea has dual effects depending on its concentration. At 200 nM, HrpWea, like HrpNea, provoked the classical defense response--active oxygen species (AOS) production and cell death. However, at 0.2 nM, HrpWea inhibited cell death and AOS production provoked by HrpNea. HrpWea probably inhibits HrpNea-induced cell death by preventing anion channel inhibition, confirming that anion channel regulation is a determinant feature of the plant response to harpins. Collectively our data show that the HrpWea harpin can act antagonistically to the classical HrpNea harpin by suppressing plant defense mechanisms. PMID- 17726063 TI - NO-mediated apoptosis in yeast. AB - Nitric oxide (NO) is a small molecule with distinct roles in diverse physiological functions in biological systems, among them the control of the apoptotic signalling cascade. By combining proteomic, genetic and biochemical approaches we demonstrate that NO and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) are crucial mediators of yeast apoptosis. Using indirect methodologies and a NO-selective electrode, we present results showing that H2O2-induced apoptotic cells synthesize NO that is associated to a nitric oxide synthase (NOS) like activity as demonstrated by the use of a classical NOS kit assay. Additionally, our results show that yeast GAPDH is a target of extensive proteolysis upon H2O2-induced apoptosis and undergoes S-nitrosation. Blockage of NO synthesis with Nomega-nitro-L-arginine methyl ester leads to a decrease of GAPDH S-nitrosation and of intracellular reactive oxygen species (ROS) accumulation, increasing survival. These results indicate that NO signalling and GAPDH S-nitrosation are linked with H2O2-induced apoptotic cell death. Evidence is presented showing that NO and GAPDH S-nitrosation also mediate cell death during chronological life span pointing to a physiological role of NO in yeast apoptosis. PMID- 17726064 TI - Nucleocytoplasmic shuttling of persistently activated STAT3. AB - Persistent activation of the transcription factor STAT3 has been detected in many types of cancer and plays an important role in tumor progression, immune evasion and metastasis. To analyze persistent STAT3 activation we coexpressed STAT3 with v-Src. We found that tyrosine phosphorylation of STAT3 by v-Src is independent of Janus kinases (Jaks), the canonical activators of STATs. The STAT3-induced feedback inhibitor, suppressor of cytokine signaling 3 (SOCS3), did not interfere with STAT3 activation by v-Src. However, the protein inhibitor of activated STAT3 (PIAS3) suppressed gene induction by persistently activated STAT3. We measured nucleocytoplasmic shuttling of STAT3 in single cells by bleaching the YFP moiety of double-labelled STAT3-CFP-YFP in the cytoplasm. Analysis of the subcellular distribution of CFP and YFP fluorescence over time by mathematical modeling and computational parameter estimation revealed that activated STAT3 shuttles more rapidly than non-activated STAT3. Inhibition of exportin-1-mediated nuclear export slowed down nucleocytoplasmic shuttling of v-Src-activated STAT3 resulting in reduced tyrosine phosphorylation, decreased induction of STAT3 target genes and increased apoptosis. We propose passage of persistently activated STAT3 through the nuclear pore complex as a new target for intervention in cancer. PMID- 17726065 TI - Sex-linked differences in pulse oxymetry. AB - The difference between genders has generated increasing interest in recent years. It is well known that women and men show differences in their respiratory system: different red blood cell counts, haemoglobin and 2,3-diphosphoglycerate plasma concentrations. Recently, further differences have been found in the ventilatory response to hypoxia and exercise and the evolution of some respiratory illnesses. In this study it was found that during rest at sea level, the haemoglobin oxygen saturation, as measured by pulse oxymetry, is slightly higher in women than in men (98.6 (SD 1.1)% versus 97.9 (SD 0.9)%; p = 0.001). These findings are consistent with other studies, which found gender differences in the transcutaneous or tissue PaO(2). The difference in oxygen saturation is not related to differences in ventilation. The disparity is modest and does not seem to produce great differences in the oxygen content of arterial blood, but combined with the different affinity of haemoglobin for oxygen or different metabolic rate, may play a role in the course of elite competition sports, high altitude ascents or the evaluation of critically ill patients. Further studies are needed to establish the degree, extent and clinical importance of these differences in the saturation of haemoglobin. PMID- 17726066 TI - Serum piperacillin/tazobactam pharmacokinetics in a morbidly obese individual. AB - OBJECTIVE: To report pharmacokinetic alterations and optimal dosing of piperacillin/tazobactam in an obese patient. CASE SUMMARY: A 39-year-old morbidly obese (weight 167 kg, body mass index 50 kg/m2) man was treated with piperacillin/tazobactam 3.375 g every 4 hours for recurrent cellulitis. The wound culture grew Groups A and B Streptococcus and rare Pseudomonas aeruginosa. Blood samples were obtained at steady-state from a peripheral venous catheter at 0, 0.5, 1, 2, 3, and 4 hours after the start of the infusion. Population pharmacokinetics were generated from a previously published data set. The serum concentrations of piperacillin/tazobactam obtained in the patient were compared with the 95% confidence interval from the representative population. Pharmacokinetic parameters such as maximal serum concentration, minimal serum concentration, average steady-state concentration, half-life, elimination rate constant, volume of distribution (V(d)), clearance, area under the curve at steadystate, and percent of time greater than the minimum inhibitory concentration (%t>MIC) were calculated and qualitatively compared between the sample and the population. DISCUSSION: Substantial differences were noted in both the absolute values at the times of sample collection and the overall concentration-versus-time profile of both compounds. The morbidly obese individual compared with the population demonstrated a reduced average serum steady-state concentration: 39.8 mg/L versus 123.6 mg/L, an increased V(d): 54.3 L versus 12.7 L, and an increased half-life: 1.4 hours versus 0.6 hours, respectively. The %t >MIC of piperacillin for the patient, assuming MICs of 2, 4, 8, 16, 32, 64, and 128 mg/L, was 100%, 100%, 90.9%, 55.4%, 19.9%, 0%, and 0%, respectively. CONCLUSIONS: Pathogens with elevated MICs may require altered dosing schemes with piperacillin/tazobactam. Future studies are warranted to assess increased dosages, more frequent dosing intervals, or continuous infusion dosing schemes for obese individuals with serious infections. PMID- 17726067 TI - Oral aloe vera-induced hepatitis. AB - OBJECTIVE: To report a case of possible oral aloe vera-induced hepatitis. CASE SUMMARY: A 73-year-old female was admitted to the hospital for acute hepatitis. Extensive laboratory testing did not reveal the cause of the patient's disease. She was asked multiple times whether she was taking any home medications, which she initially denied. It was only after an extensive medication history done by a clinical pharmacist that the patient admitted to using oral aloe vera capsules for constipation. Upon discontinuation of the oral aloe vera, liver markers of hepatotoxicity returned to normal levels. DISCUSSION: Herbal medications pose an increasing problem in patient safety, as the different types of these products and the number of patients who use them continue to grow. In the US, these products are not subject to the same regulatory scrutiny as prescription medications; thus, safety information can be difficult to obtain. In particular, hepatic toxicity due to herbal agents is poorly described in the medical literature. Aloe vera, often used topically for minor burns, can also be used orally as a laxative or an "anti-aging" agent. According to the Naranjo probability scale, the hepatotoxicity in this case was possibly related to ingestion of oral aloe vera. Additionally, using the Roussel Uclaf Causality Assessment Method for determining drug hepatotoxicity, the patient's symptoms were scored as probably caused by oral aloe vera. The more conservative designation was used in our report. CONCLUSIONS: With the widespread use of oral aloe vera and other herbal products, clinicians faced with a case of acute hepatitis that is not readily diagnosed should question patients about herbal use. PMID- 17726069 TI - Increased prevalence of subclinical hypothyroidism in common bile duct stone patients. AB - CONTEXT: Earlier, we have shown an increased prevalence of previously diagnosed hypothyroidism in common bile duct (CBD) stone patients and a delayed emptying of the biliary tract in hypothyroidism, explained partly by the missing prorelaxing effect of T(4) on the sphincter of Oddi contractility. OBJECTIVE: In this study, the prevalence of previously undiagnosed subclinical hypothyroidism in CBD stone patients was compared with nongallstone controls. PATIENTS: All patients were clinically euthyreotic and without a history of thyroid function abnormalities. CBD stones were diagnosed at endoscopic retrograde cholangiopancreatography (group 1; n = 303) or ruled out by previous medical history, liver function tests, and ultrasonography (control group II; n = 142). MAIN OUTCOME MEASURES: Serum free FT(4) and TSH (S-TSH) were analyzed; S-TSH above the normal range (>6.0 mU/liter) was considered as subclinical and S-TSH 5.0-6.0 mU/liter as borderline-subclinical hypothyroidism. RESULTS: A total of 5.3 and 5.0% (total 10.2%; 31 of 303) of the CBD stone patients were diagnosed to have subclinical and borderline-subclinical hypothyroidism, compared with 1.4% (P = 0.05) and 1.4% (total 2.8%, four of 142; P = 0.026) in the control group, respectively. In women older than 60 yr, the prevalence of subclinical hypothyroidism was 11.4% in CBD stone and 1.8% in control patients (P = 0.032) and subclinical plus borderline subclinical hypothyroidism 23.8% in CBD stone and 1.8% in control patients (P = 0.012). CONCLUSION: Subclinical hypothyroidism is more common in the CBD stone patients, compared with nongallstone controls, supporting our hypothesis that hypothyroidism might play a role in the forming of CBD stones. At minimum, women older than 60 yr with CBD stones should be screened for borderline or overt subclinical hypothyroidism. PMID- 17726068 TI - Estradiol fatty acid esters in adipose tissue and serum of pregnant and pre- and postmenopausal women. AB - CONTEXT: The 17beta-estradiol fatty acid esters are hormone derivatives with long lasting estrogenic effect. They are transported in serum lipoproteins and thought to be sequestered in adipose tissue. OBJECTIVE: Our objective was to determine the 17beta-estradiol fatty acid ester concentrations in serum and adipose tissue in women of various hormonal states. DESIGN: After several chromatographic steps separating esterified from free estradiol, time-resolved fluoroimmunoassay was used as a quantifying tool. PARTICIPANTS: Samples were obtained from pregnant women undergoing cesarean section (n = 13), or premenopausal (n = 8) and postmenopausal women (n = 6) during gynecological surgery. MAIN OUTCOME MEASURES: 17beta-Estradiol and 17beta-estradiol fatty acid ester concentrations in serum, and visceral and sc adipose tissue were examined. RESULTS: The ratio of esterified to free estradiol in plasma increased with decreasing estradiol level from 0.5% in pregnant, to 15% in premenopausal and 110% in postmenopausal women. Estradiol esters constituted about 10% of the free estradiol present in adipose tissue in pregnancy. In nonpregnant women, most of the adipose tissue estradiol was in esterified form, the median ester to free ratio being elevated to 150 490%. After menopause, the overwhelming majority of estradiol in both free and esterified form was present in adipose tissue. CONCLUSIONS: The overall higher ester to free estradiol ratio in adipose tissue than in serum indicates active esterification capacity in adipose tissue. The predominance of esterified and free estradiol in postmenopausal adipose tissue compared with serum suggests in situ production and storage. Whether the estradiol esters have an independent physiological role in adipose tissue remains to be clarified. PMID- 17726070 TI - Serum 25-hydroxyvitamin D measurement in a large population survey with statistical harmonization of assay variation to an international standard. AB - CONTEXT: An automated application of Immunodiagnostic Systems Limited (IDS) OCTEIA 25-hydroxyvitamin D [25(OH)D] enzyme immunoassay was developed for analyses of 25(OH)D in more than 7000 participants of the 1958 cohort. Variation between 25(OH)D assays hampers between-study comparisons and the definition of relevant cutoffs for hypovitaminosis D. OBJECTIVE: The objective of the study was to evaluate the importance of assay variation on the estimated prevalence of hypovitaminosis D and assess the use of statistical harmonization to overcome the observed differences. DESIGN: Agreement analyses were performed between two commercial 25(OH)D assays (IDS enzyme immunoassay and Diasorin RIA), with validation using performance data from Vitamin D External Quality Assessment Scheme (DEQAS). SETTING: The study was conducted in England, Scotland, and Wales. PARTICIPANTS: Members of the 1958 British birth cohort participated in the study. MAIN OUTCOME MEASURES: 25(OH)D was measured both by IDS and Diasorin RIA in 781 samples. Additional quality control data were obtained through participation in DEQAS (five distributions throughout the survey). RESULTS: Average 25(OH)D concentrations by IDS were -15.7 and -13.7 nmol/liter lower, compared with Diasorin or DEQAS mean, respectively (both P < 0.0001). Graphical examination demonstrated a dose-related bias between IDS with Diasorin and DEQAS mean, but log transformation removed the bias. After using the log difference between the measurements as an adjustment factor, there were no differences in average 25(OH)D concentrations (P >or= 0.21 for comparison of IDS with Diasorin or DEQAS) and estimates for hypovitaminosis D obtained by IDS were similar to Diasorin. CONCLUSIONS: Differences between assays have implications for public health messages about hypovitaminosis D. Harmonization of results with DEQAS enabled the use of previously determined cutoffs for hypovitaminosis D. PMID- 17726071 TI - Imaging medullary thyroid carcinoma with persistent elevated calcitonin levels. AB - PURPOSE: Because calcitonin level remains elevated after initial treatment in many medullary thyroid carcinoma (MTC) patients without evidence of disease in the usual imaging work-up, there is a need to define optimal imaging procedures. PATIENTS AND METHODS: Fifty-five consecutive elevated calcitonin level MTC patients were enrolled to undergo neck and abdomen ultrasonography (US); neck, chest, and abdomen spiral computed tomography (CT); liver and whole-body magnetic resonance imaging (MRI); bone scintigraphy; and 2-[fluorine-18]fluoro-2-deoxy-d glucose (FDG) positron emission tomography (PET)/CT scan (PET). RESULTS: Fifty patients underwent neck US, CT, and PET, and neck recurrence was demonstrated in 56, 42, and 32%, respectively. Lung and mediastinum lymph node metastases in the 55 patients were demonstrated in 35 and 31% by CT and in 15 and 20% by PET. Liver imaging with MRI, CT, US, and PET in 41 patients showed liver in 49, 44, 41, and 27% patients, respectively. Bone metastases in 55 patients were demonstrated in 35% by PET, 40% by bone scintigraphy, and 40% by MRI; bone scintigraphy was complementary with MRI for axial lesions but superior for the detection of peripheral lesions. Ten patients had no imaged tumor site despite elevated calcitonin level (median 196 pg/ml; range 39-816). FDG uptake in neoplastic foci was higher in progressive patients but with a considerable overlap with stable ones. CONCLUSION: The most efficient imaging work-up for depicting MTC tumor sites would consist of a neck US, chest CT, liver MRI, bone scintigraphy, and axial skeleton MRI. FDG PET scan appeared to be less sensitive and of low prognostic value. PMID- 17726073 TI - Transcriptional inhibition of oxytocin receptor expression in human myometrial cells by melatonin involves protein kinase C signaling. AB - CONTEXT: Our laboratory recently characterized the expression of the melatonin receptors in the human myometrium and showed that the expression of these receptors is suppressed during late pregnancy. OBJECTIVE: In an effort to understand better the significance of melatonin in the human myometrium, we explored the mechanisms through which this hormone influences the expression of the oxytocin receptor in vitro. DESIGN: The stable melatonin analog iodomelatonin was presented to cultured telomerase-immortalized myometrial cells of the human telomerase reverse transcriptase line under physiological doses and durations. Pharmacological inhibitors of melatonin binding, gene transcription, phospholipase C, and protein kinase C signaling were used to define the mechanism of melatonin action. RESULTS: Our results reveal that melatonin significantly inhibits oxytocin receptor mRNA expression primarily via the melatonin 2 receptor. The melatonin-dependent decrease in oxytocin receptor transcripts involves suppression of gene transcription rather than enhanced rates of transcript degradation. Melatonin effects were abolished by pretreating the cells with the phospholipase C inhibitor U73122 or the protein kinase C inhibitor C1. CONCLUSIONS: Melatonin, like oxytocin, can negatively regulate oxytocin receptor transcription in human myometrial cells via modulation of protein kinase C signaling. This is consistent with the hypothesis that the reduced melatonin receptor expression during late pregnancy, which occurs at a time when oxytocin receptors are up-regulated, may be physiologically important for the subsequent timing of labor. PMID- 17726072 TI - Phenotypic effects of null and haploinsufficiency of acid-labile subunit in a family with two novel IGFALS gene mutations. AB - CONTEXT: IGF-I deficiency may result from impairment of GH secretion or action, or from defects in IGF-I synthesis, transport, or action. Complete deficiency of the acid-labile subunit (ALS), previously described in two male patients, the only known inherited alteration in IGF-I transport, is characterized by severe circulating IGF-I and IGF binding protein (IGFBP)-3 deficiency with only mild growth retardation. OBJECTIVE: Our objective was to study the characterization, at biochemical and molecular levels, of the cause for severe circulating IGF-I and IGFBP-3 deficiency in a male patient with mild growth retardation. PATIENTS: We report an adolescent male with delayed growth and pubertal development (Tanner stage I, -2.00 sd score for height at the age of 15.3 yr), profound circulating IGF-I and IGFBP-3 deficiency, and poor response to GH treatment. RESULTS: The index case, as well as one of his brothers, and his sister were found to be compound heterozygotes for two novel IGFALS gene mutations: C540R, a missense point mutation; and S195_197Rdup, a 9-bp duplication. The parents and youngest brother were found to be carriers for one of these two mutations. The three affected siblings had marked reduction of IGF-I and IGFBP-3 levels, undetectable serum levels of ALS, inability to form ternary complexes, and moderate insulin resistance. All of them attained a normal near-adult height (between -1.0 and 0.5 sd score), which was nonetheless lower than that of their heterozygous brother. The IGF system was only modestly affected in the heterozygous carriers. CONCLUSIONS: This study confirms the critical role of ALS in forming ternary complexes and the maintenance of normal levels of IGF-I and IGFBP-3. Insulin resistance, pubertal delay in male patients, and poor GH responsiveness seem to be frequent findings in ALS deficiency. However, haploinsufficiency of the IGFALS gene has no discernible clinical effects with only modest impact on the IGF system. PMID- 17726075 TI - Exon splice enhancer mutation (GH-E32A) causes autosomal dominant growth hormone deficiency. AB - CONTEXT AND OBJECTIVE: Alteration of exon splice enhancers (ESE) may cause autosomal dominant GH deficiency (IGHD II). Disruption analysis of a (GAA) (n) ESE motif within exon 3 by introducing single-base mutations has shown that single nucleotide mutations within ESE1 affect pre-mRNA splicing. DESIGN, SETTING, AND PATIENTS: Confirming the laboratory-derived data, a heterozygous splice enhancer mutation in exon 3 (exon 3 + 2 A-->C) coding for GH-E32A mutation of the GH-1 gene was found in two independent pedigrees, causing familial IGHD II. Because different ESE mutations have a variable impact on splicing of exon 3 of GH and therefore on the expression of the 17.5-kDa GH mutant form, the GH-E32A was studied at the cellular level. INTERVENTIONS AND RESULTS: The splicing of GH E32A, assessed at the protein level, produced significantly increased amounts of 17.5-kDa GH isoform (55% of total GH protein) when compared with the wt-GH. AtT 20 cells coexpressing both wt-GH and GH-E32A presented a significant reduction in cell proliferation as well as GH production after forskolin stimulation when compared with the cells expressing wt-GH. These results were complemented with confocal microscopy analysis, which revealed a significant reduction of the GH E32A-derived isoform colocalized with secretory granules, compared with wt-GH. CONCLUSION: GH-E32A mutation found within ESE1 weakens recognition of exon 3 directly, and therefore, an increased production of the exon 3-skipped 17.5-kDa GH isoform in relation to the 22-kDa, wt-GH isoform was found. The GH-E32A mutant altered stimulated GH production as well as cell proliferation, causing IGHD II. PMID- 17726074 TI - Growth hormone treatment improves markers of systemic nitric oxide bioavailability via insulin-like growth factor-I. AB - CONTEXT AND OBJECTIVE: Impaired nitric oxide (NO) bioavailability and low levels of circulating endothelial progenitor cells (EPC) are correlated to an increased risk for development of cardiovascular diseases. We investigated whether improved systemic NO bioavailability and increased levels of EPC after GH treatment are related and mediated by the IGF-I. DESIGN, PATIENTS, AND RESULTS: Healthy middle aged volunteers (n = 16) were treated for 10 d with recombinant human GH. Before and after GH treatment, we analyzed markers of NO bioavailability and EPC levels. GH treatment was responded by significant increases in plasma IGF-I levels. Urinary cGMP levels were increased and diastolic blood pressure reduced after GH treatment (P < 0.05). Likewise, plasma nitrate and nitrite levels were increased, whereas the NO synthase inhibitor asymmetric dimethylarginine was reduced. Correspondingly, IGF-I treatment increased expression of the asymmetric dimethylarginine-metabolizing enzyme dimethylarginie dimethylaminohydrolase-1 and dimethylarginie dimethylaminohydrolase-2 in cultured human endothelial cells. IGF I levels correlated with cGMP concentrations (r = 0.51; P < 0.05). EPC numbers were increased after GH treatment and correlated with markers for NO bioavailability. These findings were also observed in mice treated with GH for 7 d. GH treatment additionally increased aortic endothelial NO synthase expression of mice. Importantly, blocking of the IGF-I receptor in vivo abolished the GH mediated effects on markers of increased NO bioavailability. CONCLUSIONS: GH treatment induced markers of increased NO bioavailability and enhanced circulating EPC numbers in healthy volunteers. Animal data demonstrate increased NO availability to be mediated via an increase in IGF-I plasma levels. Thus, GH treatment enhances systemic NO bioavailability via IGF-I and may be beneficial in certain cardiovascular diseases. PMID- 17726076 TI - Acute sex steroid withdrawal reduces insulin sensitivity in healthy men with idiopathic hypogonadotropic hypogonadism. AB - CONTEXT: Evidence suggests that testosterone (T) influences insulin sensitivity in men. The mechanism of this effect is unclear but is thought to involve changes in body composition. OBJECTIVE: The aim of this study was to determine whether acute sex steroid withdrawal decreases insulin sensitivity in young, healthy men with idiopathic hypogonadotropic hypogonadism (IHH). DESIGN: This was a 2-wk prospective study. SETTING: The study was conducted at a General Clinical Research Center. PATIENTS: Twelve men with IHH (age 40.8 +/- 2.8 yr) were studied: 1) on hormone replacement with normal T levels and 2) 2 wk after discontinuing therapy. MAIN OUTCOME MEASURES: Each evaluation comprised a 75-g oral glucose tolerance test with assessment of insulin sensitivity (fasting insulin levels, homeostatic model assessment for insulin resistance, and Matsuda insulin sensitivity index) and insulin secretion (corrected insulin response). Serum cortisol, leptin, adiponectin, free fatty acids, IL-6, C-reactive protein, and TNF-alpha levels were also measured. RESULTS: Body mass index was unchanged (27.1 +/- 1.1 to 27.2 +/- 1.1 kg/m(2)). Serum T levels decreased from 529 +/- 65 to 28 +/- 8 ng/dl (P < 0.00005). Fasting insulin levels increased from 4.9 +/- 0.7 to 6.2 +/- 0.6 microU/ml (P = 0.005), homeostatic model assessment of insulin resistance increased from 1.07 +/- 0.2 to 1.4 +/- 1.01 (P < 0.005), and insulin sensitivity index decreased from 11.0 +/- 2.3 to 7.5 +/- 0.7 (P < 0.05). There was a trend for fasting glucose levels to increase, 86.7 +/- 1.3 to 90.8 +/- 1.7 mg/dl (P = 0.09). IL-6 levels increased from 1.2 +/- 0.2 to 2.4 +/- 0.5 pg/ml (P < 0.01), whereas TNF-alpha levels decreased from 1.0 +/- 0.1 to 0.6 +/- 0.1 pg/ml (P < 0.05). No other significant changes were observed. CONCLUSIONS: 1) Acute sex steroid withdrawal reduces insulin sensitivity in young healthy IHH men. 2) The acuity of the hypogonadism and absence of changes in body mass index or leptin levels suggest that sex steroids modulate insulin sensitivity in the absence of apparent or detectable changes in body composition. PMID- 17726077 TI - Insulin resistance is unrelated to circulating retinol binding protein and protein C inhibitor. AB - CONTEXT: Recent data suggest that circulating retinol-binding protein (RBP) might be involved in the pathogenesis of insulin resistance. Moreover, protein C inhibitor (PCI), which specifically binds retinoic acid, was found to be increased in myocardial infarction survivors who are also insulin resistant. OBJECTIVE: The objective of this study was to investigate the association of insulin resistance with RBP factors and PCI active antigen. DESIGN AND SETTING: This was a clinical study. PATIENTS: Nondiabetic humans with high (IS; n = 20, 14 females, six males, aged 47.2 +/- 1.9 yr, body mass index 26 +/- 1 kg/m(2)) and low (IR; n = 20, 14 females, six males, aged 45.5 +/- 1.7 yr, body mass index 28 +/- 1 kg/m(2)) insulin-stimulated glucose-disposal (M) participated in this study. MAIN OUTCOME MEASURES: M was measured by 2-h hyperinsulinemic (40 mU.min( 1).m(-2))-isoglycemic clamp tests. Measurements of RBP were performed using a nephelometric method and validated using quantitative Western blotting. RESULTS: M (80-120 min) was higher in IS (10.9 +/- 0.6 mg.min(-1).kg(-1)) than IR (4.0 +/- 0.2; P < 10(-12)). Fasting plasma RBP concentrations were comparable between IS and IR measured by both nephelometry (IS: 4.4 +/- 0.3; IR: 4.6 +/- 0.3 mg/dl, P = 0.6) and quantitative Western blot (IS 7.9 +/- 0.5, IR 8.3 +/- 0.6 mg/dl; P = 0.6). Fasting plasma PCI active antigen was similar in both groups. Plasma RBP and PCI were not significantly related to M. RBP was positively correlated with uric acid (r = 0.488, P = 0.003), triglycerides (r = 0.592, P < 0.001), prealbumin (r = 0.63, P < 0.0001), and vitamin A (r = 0.75, P < 10(-6)). CONCLUSIONS: Our data demonstrate that healthy, insulin-resistant humans do not show altered plasma retinol binding factors, such as RBP and PCI. Both do not significantly correlate with insulin sensitivity. Thus, our findings do not support the hypothesis of insulin sensitivity modulation by proteins involved in retinol transport. PMID- 17726078 TI - Anti-Mullerian hormone is a sensitive serum marker for gonadal function in women treated for Hodgkin's lymphoma during childhood. AB - PURPOSE: The aim of this study was to evaluate the long-term effects of combination chemotherapy treatment for girls with Hodgkin's lymphoma (HL) on gonadal function using anti-Mullerian hormone (AMH) and inhibin B as ovarian reserve parameters. PATIENTS AND METHODS: LH, FSH, inhibin B, and AMH were measured in 32 women treated from 1974 to 1998 for pediatric HL with chemotherapy, with the intention to avoid radiotherapy. All patients [median age 25.0 yr (range 19.2-40.4 yr)] were in complete remission with a median follow-up time of 14.0 yr (range 5.7-24.5 yr) after therapy. All patients were treated with combination chemotherapy doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) or EBVD with or without mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). Because of incomplete remission or relapse, involved field radiotherapy was needed in seven of 32 women. Results were compared with a healthy control group. RESULTS: Patients treated with six or more cycles of MOPP combination chemotherapy had significantly higher levels of FSH and lower serum levels of inhibin B and AMH, compared with healthy women [FSH, 17.0 vs. 6.0 U/liter (P < 0.05); inhibin B, 23.0 vs. 112.5 ng/liter (P < 0.01); AMH, 0.39 vs. 2.10 microg/liter (P < 0.01)]. AMH was also significantly lower, compared with women treated without MOPP (median 0.39 vs. 1.40 microg/liter; P = 0.01). CONCLUSIONS: Women treated during childhood for HL with MOPP seem to have a distinctly lower ovarian reserve as measured by lower AMH values at early adulthood, compared with healthy women. Moreover, AMH seems to be the only predictor that is sufficiently sensitive to detect this decrease in ovarian reserve. PMID- 17726079 TI - Effect of Iodide on Human Choriogonadotropin, Sodium-Iodide Symporter Expression, and Iodide Uptake in BeWo Choriocarcinoma Cells. AB - CONTEXT: Active placental transport of maternal iodide by the thyroidal sodium iodide symporter (NIS) provides an essential substrate for fetal thyroid hormone synthesis. NIS is expressed in trophoblast and is regulated by human choriogonadotropin (hCG). In thyroid, iodide down-regulates expression of several genes including NIS. Placentas of iodine-deficient rats demonstrate up-regulation of NIS mRNA, suggesting a role for iodide in regulating placental NIS. OBJECTIVES AND METHODS: The objectives were to examine effects of iodide on expression of NIS and hCG in BeWo choriocarcinoma cells. Gene expression was studied by quantitative real-time PCR. Effects on NIS protein expression were assessed by Western blotting. Functional activity of NIS was measured by (125)I uptake. Expression of hCG protein was assessed by immunoassay of secreted hormone. RESULTS: Iodide inhibited NIS mRNA and membrane protein expression as well as (125)I uptake, which were paralleled by decreased betahCG mRNA expression and protein secretion. Iodide had no effects on pendrin expression. Addition of hCG increased NIS mRNA expression. This effect was partially inhibited by addition of iodide. The inhibitory effects of iodide on NIS mRNA expression were abolished by propylthiouracil and dithiothreitol. CONCLUSIONS: We conclude that expression of placental NIS is modulated by maternal iodide. This may occur through modulation of hCG effects on NIS and hCG gene expression. PMID- 17726080 TI - Effect of macronutrient composition on postprandial peptide YY levels. AB - BACKGROUND: Peptide YY (PYY) is released from the distal small intestine and colon after meals and reduces appetite by increasing satiety. The amount of PYY released is proportional to calories ingested. Fat ingestion has also been reported to stimulate PYY release. OBJECTIVE: The objective of the study was to determine whether macronutrient composition influences postprandial serum PYY levels by comparing 1 wk of a weight-maintenance low-carbohydrate, high-fat (LCHF) diet with a low-fat, high-carbohydrate (LFHC) diet. METHODS: In this randomized crossover study, 18 obese subjects (14 females, 4 males, mean body mass index 35.6 +/- 2.9 kg/m(2)) were randomly assigned initially to 1 wk of a weight-maintenance LCHF or LFHC diet, after which a test meal of identical composition was given and serum PYY levels were assessed for 2.5 h postprandially. After a 1-wk washout period, subjects were crossed over and retested. RESULTS: After 1 wk, mean postprandial area under the curve PYY after the LCHF test meal was 1.5-fold greater than after the LFHC test meal (P < 0.001). The LCHF diet led to 55% higher levels of postprandial serum PYY levels, compared with the LFHC diet (P = 0.005). CONCLUSIONS: These data show that a LCHF diet stimulates PYY secretion more than a LFHC diet in obese individuals. PMID- 17726082 TI - Relationships of urinary adrenal steroids at age 8 years with birth weight, postnatal growth, blood pressure, and glucose metabolism. AB - INTRODUCTION: Overactivity of the hypothalamic-pituitary-adrenal axis through a program set by early growth patterns is hypothesized to lead to central obesity, insulin resistance, and hypertension. We therefore examined links between adrenal steroid production and birth weight, rapid early growth, and body mass index (BMI), blood pressure, waist circumference, and resistance to insulin in early childhood through the action of adrenal steroids. METHODS: Timed overnight urine samples were collected in 461 children from a large representative birth cohort. In total 244 boys and 188 girls aged 8.2-8.4 yr completed the protocol. The excretion rates of individual steroids were measured to determine total androgen and cortisol metabolites. Indices of activity of 5alpha-androgen reduction of androgens and cortisol metabolites and 11beta-hydroxy steroid dehydrogenase activity were calculated. RESULTS: In both boys and girls, total urinary androgen and cortisol metabolites were positively related to current height, weight, BMI, and waist circumference. Girls had higher urine androgen metabolite levels and 5alpha-androgen indexes than boys, and in girls higher androgen metabolite excretion was associated with lower birth weight and faster postnatal weight gain. After adjustment for current BMI, total cortisol metabolites and 11beta hydroxy steroid dehydrogenase index were not related to birth weight or postnatal weight gain in either sex. CONCLUSIONS: These data confirm early growth associations in this cohort seen with plasma levels of adrenal androgens at age 8 yr, at least in girls. Larger studies and follow-up during puberty are needed to exclude the possibility of programming of cortisol metabolism by early growth. PMID- 17726081 TI - Effects of atorvastatin on bone in postmenopausal women with dyslipidemia: a double-blind, placebo-controlled, dose-ranging trial. AB - CONTEXT: In preclinical models, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase have been shown to positively affect bone remodeling balance. Observational studies and secondary analyses from lipid-lowering trials have yielded inconsistent results regarding the effect of these agents on bone mineral density and fracture risk. OBJECTIVE: Our objective was to determine whether clinically significant skeletal benefits result from hydroxymethylglutaryl coenzyme A reductase inhibition in postmenopausal women. DESIGN AND SETTING: We conducted a prospective, randomized, double-blind, placebo-controlled, dose ranging comparative clinical trial at 62 sites in the United States. PARTICIPANTS: Participants included 626 postmenopausal women with low-density lipoprotein cholesterol levels of at least 130 mg/dl (3.4 mmol/liter) and less than 190 mg/dl (4.9 mmol/liter), and lumbar (L1-L4) spine bone mineral density T score between 0.0 and -2.5. INTERVENTION: Once-daily placebo or 10, 20, 40, or 80 mg atorvastatin was administered. MAIN OUTCOME MEASURES: We assessed percent change from baseline in lumbar (L1-L4) spine bone mineral density with each dose of atorvastatin compared with placebo. RESULTS: At 52 wk, there was no significant difference between each atorvastatin and placebo group or change from baseline at any tested dose of atorvastatin or placebo in lumbar (L1-L4) spine bone mineral density. Nor did atorvastatin produce a significant change in bone mineral density at any other site. Changes in biochemical markers of bone turnover did not differ significantly between each atorvastatin and placebo group. All doses of atorvastatin were generally well tolerated, with similar incidences of adverse events across all dose groups and placebo. CONCLUSIONS: Clinically relevant doses of atorvastatin that lower lipid levels had no effect on bone mineral density or biochemical indices of bone metabolism in this study, suggesting that such oral agents are not useful in the prevention or treatment of osteoporosis. PMID- 17726084 TI - Impact sibutramine therapy in children with hypothalamic obesity or obesity with aggravating syndromes. AB - OBJECTIVE: Behavioral treatment of children suffering from hypothalamic obesity or uncomplicated obesity in combination with syndromes that aggravate this condition has proven to be ineffective. The combination of comorbidities and severe obesity lower the quality of these children's lives drastically. The present goal was to determine whether treatment with sibutramine has a beneficial effect on such children. DESIGN AND SUBJECTS: A double-blind, placebo-controlled, cross-over study (20 + 20 wk), followed by a 6-month open phase, was performed. The primary indicator of efficacy was the body mass index (BMI) sd score (SDS) value, which was analyzed using an ANOVA repeated-measures design [intention to treat (ITT)]. The 50 children (7-20 yr of age) involved included 22 with hypothalamic obesity and 28 with uncomplicated obesity plus aggravating syndromes. Forty-five patients completed the first phase, and 42 participated in the entire study. RESULTS: The group that initially received the placebo demonstrated an insignificant decrease (-0.06) in BMI SDS during this treatment but a significant decrease (-0.68; P < 0.001) when treated with sibutramine. The other group demonstrated a reduction in their BMI SDS of -0.72 during administration of sibutramine and a rebound of +0.43 when placed on the placebo (P < 0.001 in both cases). The response of children with hypothalamic obesity was also significant but was less pronounced than that of children with nonhypothalamic obesity. During the open phase, a continuous reduction in weight was observed. The treatment was tolerated well. CONCLUSION: The clinically and statistically significant weight reduction caused by sibutramine in this short term study indicates that treatment of hypothalamic and syndromal obesity with this drug may be beneficial. PMID- 17726085 TI - Serum retinol-binding protein 4 concentration and its ratio to serum retinol are associated with obesity and metabolic syndrome components in children. AB - CONTEXT: Although retinol-binding protein (RBP)-4 concentrations are elevated in animal models of obesity and insulin resistance (IR), the link between RBP4 and IR in humans is less clear. There are few published data on RBP4 levels in overweight children, and most previous studies did not control for vitamin A (VA) status and/or subclinical inflammation. OBJECTIVE: The objective of the study was to measure serum RBP4, serum retinol (SR), the RBP4-to-SR molar ratio, and dietary VA intakes in normal-weight and overweight children and investigate the relationship of these variables to IR, subclinical inflammation, and the metabolic syndrome in this age group. DESIGN: This was a cross-sectional study. SETTING: The study was conducted in Northern Switzerland. PATIENTS: Patients included 6- to 14-yr-old normal-weight, overweight, and obese children (n = 79). MAIN OUTCOME MEASURES: Body mass index, body fat percentage, waist-to-hip ratio, dietary VA intakes, serum RBP4, and SR were determined. IR was assessed using fasting insulin and the quantitative insulin sensitivity check index, and components of the metabolic syndrome and indices of subclinical inflammation were measured. RESULTS: Only 3% of children had low VA status. Independent of age, VA intakes, and C-reactive protein, body mass index, body fat percentage, and waist to-hip ratio were significant predictors of RBP4, SR, and RBP4/SR. Independent of adiposity, RBP4 and RBP4/SR were significantly correlated with serum triglycerides, and RBP4/SR was correlated with fasting insulin. The RBP4-to-SR ratio more strongly correlated with components of the metabolic syndrome than serum RBP4. CONCLUSION: Independent of subclinical inflammation and vitamin A intakes, serum RBP4 and the RBP4-to-SR ratio are correlated with obesity, central obesity, and components of the metabolic syndrome in prepubertal and early pubertal children. PMID- 17726083 TI - Body mass index predicts aldosterone production in normotensive adults on a high salt diet. AB - CONTEXT: The mechanisms underlying obesity-mediated cardiovascular disease are not fully understood. Aldosterone and insulin resistance both are associated with obesity and cardiovascular disease. OBJECTIVES: The objectives of this study were to test the hypotheses that aldosterone production is elevated and associated with insulin resistance in overweight adults on a high-sodium diet. PARTICIPANTS/INTERVENTIONS: Healthy normotensive adults were categorized as lean body mass index (BMI) less than 25 kg/m(2) (n = 63) or overweight BMI 25 kg/m(2) or greater (n = 57). After 7 d of a high-sodium diet, participants fasted overnight and remained supine throughout hemodynamic and laboratory assessments and angiotensin II (AngII) stimulation. RESULTS: The overweight group, compared with the lean group, had higher 24-h urinary aldosterone (9.0 +/- 0.8 vs. 6.6 +/- 0.5 microg per 24 h; P = 0.003) and higher AngII-stimulated serum aldosterone (11.4 +/- 1.0 vs. 9.0 +/- 0.6 ng/dl; P = 0.04). There were no differences in 24-h urinary cortisol or sodium or supine measurements of plasma renin activity, serum aldosterone, or serum potassium. The homeostasis model assessment of insulin resistance was predicted by urinary aldosterone excretion (r = 0.32, P = 0.03) and serum aldosterone response to AngII stimulation (r = 0.28, P = 0.02) independent of age and BMI. CONCLUSION: Urinary aldosterone excretion and AngII stimulated aldosterone are increased in overweight, compared with lean, normotensive adults. The correlation of these measures of aldosterone production with insulin resistance suggests a potential role for aldosterone in the pathophysiology of obesity-mediated insulin resistance. PMID- 17726086 TI - Intramuscular testosterone treatment in elderly men: evidence of memory decline and altered brain function. AB - CONTEXT: Recent clinical trials of im testosterone in eugonadal men suggest positive effects on verbal memory, but other studies find no effect. OBJECTIVE: Our objective was to determine whether supraphysiological testosterone influences verbal memory and brain function during a verbal memory task in healthy eugonadal older men. PATIENTS, DESIGN, AND SETTING: Fifteen cognitively normal men, aged 66 86 yr, participated in a randomized, double-blind, placebo-controlled crossover trial involving 9 months of participation per participant at a hospital-based research facility. INTERVENTION: We used testosterone enanthate (200 mg im every other week for 90 d) crossed over with placebo (sesame oil vehicle im) with a 90 d washout between treatments. MAIN OUTCOME MEASURES: Performance was assessed on a standardized verbal memory test, and brain activity (relative glucose metabolic rates) in medial temporal and frontal regions was measured with positron emission tomography during a verbal memory task. RESULTS: Treatment increased total testosterone by 241%. Behavioral results showed a significant decrease in short delay verbal memory with treatment (P < 0.05, effect size = 0.59 sd) and a nonsignificant decrease on a composite verbal memory measure (P = 0.09, effect size = 0.48 sd). Positron emission tomography scans revealed decreased relative activity in ventromedial temporal cortex (i.e. right amygdala/entorhinal cortex) and increased relative activity in bilateral prefrontal cortex with treatment. CONCLUSIONS: Decreased verbal memory and altered relative activity in medial temporal and prefrontal regions suggest possible detrimental effects of supraphysiological testosterone supplementation in elderly men. The results do not rule out potential benefits with other regimens, cognitive tests, or populations. PMID- 17726088 TI - H2A.Bbd: a quickly evolving hypervariable mammalian histone that destabilizes nucleosomes in an acetylation-independent way. AB - Molecular evolutionary analyses revealed that histone H2A.Bbd is a highly variable quickly evolving mammalian replacement histone variant, in striking contrast to all other histones. At the nucleotide level, this variability appears to be the result of a larger amount of nonsynonymous variation, which affects to a lesser extent, the structural domain of the protein comprising the histone fold. The resulting amino acid sequence diversity can be predicted to affect the internucleosomal and intranucleosomal histone interactions. Our phylogenetic analysis has allowed us to identify several of the residues involved. The biophysical characterization of nucleosomes reconstituted with recombinant mouse H2A.Bbd and their comparison to similar data obtained with human H2A.Bbd clearly support this notion. Despite the high interspecific amino acid sequence variability, all of the H2A.Bbd variants exert similar structural effects at the nucleosome level, which result in an unfolded highly unstable nucleoprotein complex. Such structure resembles that previously described for the highly dynamically acetylated nucleosomes associated with transcriptionally active regions of the genome. Nevertheless, the structure of nucleosome core particles reconstituted from H2A.Bbd is not affected by the presence of a hyperacetylated histone complement. This suggests that replacement by H2A.Bbd provides an alternative mechanism to unfold chromatin structure, possibly in euchromatic regions, in a way that is not dependent on acetylation. PMID- 17726087 TI - Immunological and structural properties of a pectic polymer from Glinus oppositifolius. AB - The aim of this paper was to further elucidate the structure and the immunomodulating properties of the pectic polymer GOA2, previously isolated from Glinus oppositifolius. Enzymatic treatment of GOA2 by endo-alpha-d-(1 --> 4) polygalacturonase led to the isolation of three pectic subunits, GOA2-I, GOA2-II, and GOA2-III, in addition to oligogalacturonides. GOA2-I was shown to consist of 1,2-linked Rhap and 1,4-linked GalpA in an approximately 1:1 ratio, and NMR analysis showed that the monomers were linked together in a strictly alternating manner. The galactose units in GOA2-I were found as terminal-, 1,3-, 1,6-, 1,4-, 1,3,4-, and 1,3,6-linked residues, while the arabinofuranosyl existed mainly as terminal- and 1,5-linked units. A rhamnogalacturonan-I type structure was suggested being the predominant part of GOA2-I. According to linkage analysis GOA2-II and GOA2-III contained glycosidic linkages characteristic for rhamnogalacturonan-II type structures. GOA2 was shown by sedimentation velocity in the analytical ultracentrifuge, to have a broad degree of polydispersity with a mode s(20,w) value of approximately 1.9 S, results reinforced by atomic force microscopy measurements. The polydispersity, as manifested by the proportion of material with s(20,w) > 3 S, decreased significantly with enzyme treatment. The abilities of GOA2, GOA2-I, GOA2-II, and GOA2-III to induce the proliferation of B cells, and to exhibit complement fixing activities were tested. In both test systems, GOA2-I showed significantly greater effects compared to its native pectin GOA2. GOA2-I was in addition shown to exhibit a more potent intestinal immune stimulating activity compared to GOA2. The ability of GOA2 to induce secretion of proinflammatory cytokines was examined. Marked upregulations in mRNA for IL-1beta from rat macrophages and IFN-gamma from NK cells were found. PMID- 17726089 TI - Cloning and in vivo expression of vascular endothelial growth factor receptor 2 (Flk1) in the naturally hypoxia-tolerant subterranean mole rat. AB - Vascular endothelial growth factor receptor (VEGF) plays a critical role in blood vessel formation and affects nerve growth and survival. VEGF receptor 2 (Flk1) functions as the major signal transducer of angiogenesis, mediating VEGF induction of endothelial tubulogenesis. We have cloned and analyzed expression of Flk1 in the blind subterranean mole rat Spalax ehrenbergi. Spalax experience abrupt and sharp changes in oxygen supply in their sealed underground niche and, hence, are genetically adapted to hypoxia and serve as a unique, natural mammalian model organism for hypoxia tolerance. Spalax Flk1 is relatively conserved at the nucleic acid and amino acid level compared to human, mouse, and rat orthologs. Reverse transcription-quantitative polymerase chain reaction was used to analyze Flk1 expression in muscle and brain of animals exposed to ambient or variant hypoxic oxygen levels at multiple stages of development. Transcript levels were compared with those obtained from Rattus, a primary model for human physiology. Our findings demonstrate that under normoxic conditions Flk1 patterns of expression correlate well with our previous investigations of VEGF expression. Exposure to hypoxic conditions resulted in divergent patterns of Flk1 expression between Spalax and Rattus and between muscle and brain. It appears that the regulatory mechanisms differentiating expression between the species and between tissues are most likely unique, suggesting that Flk1 expression may be regulated by multiple processes, including both angiogenesis and neurogenesis. PMID- 17726090 TI - GA-binding protein regulates KIS gene expression, cell migration, and cell cycle progression. AB - The cyclin-dependent kinase inhibitor p27(Kip1) arrests cell cycle progression through G1/S phases and is regulated by phosphorylation of serine/threonine residues. Recently, we identified the serine/threonine kinase, KIS, which phosphorylates p27(Kip1) on serine 10 leading to nuclear export of p27(Kip1) and protein degradation. However, the molecular mechanisms of transcriptional activation of the human KIS gene and its biological activity are not known. We mapped the transcription initiation site approximately 116 bp 5' to the translation start site, and sequences extending to -141 were sufficient for maximal promoter activity. Mutation in either of two Ets-binding sites in this region resulted in an approximately 75-80% decrease in promoter activity. These sites form at least 3 specific complexes, which contained GA-binding protein (GABP). Knocking down GABPalpha by siRNA in vascular smooth muscle cells (VSMCs) diminished KIS gene expression and reduced cell migration. Correspondingly, in serum stimulated GABPalpha-deficient mouse embryonic fibroblasts (MEFs), KIS gene expression was also significantly reduced, which was associated with an increase in p27(Kip1) protein levels and a decreased percentage of cells in S-phase. Consistent with these findings, following vascular injury in vivo, GABPalpha heterozygous mice demonstrated reduced KIS gene expression within arterial lesions and these lesions were significantly smaller compared to GABP+/+ mice. In summary, serum-responsive GABP binding to Ets-binding sites activates the KIS promoter, leading to KIS gene expression, cell migration, and cell cycle progression. PMID- 17726091 TI - Accuracy of electrocardiography in diagnosis of left ventricular hypertrophy in arterial hypertension: systematic review. AB - OBJECTIVE: To review the accuracy of electrocardiography in screening for left ventricular hypertrophy in patients with hypertension. DESIGN: Systematic review of studies of test accuracy of six electrocardiographic indexes: the Sokolow-Lyon index, Cornell voltage index, Cornell product index, Gubner index, and Romhilt Estes scores with thresholds for a positive test of > or =4 points or > or =5 points. DATA SOURCES: Electronic databases ((Pre-)Medline, Embase), reference lists of relevant studies and previous reviews, and experts. STUDY SELECTION: Two reviewers scrutinised abstracts and examined potentially eligible studies. Studies comparing the electrocardiographic index with echocardiography in hypertensive patients and reporting sufficient data were included. DATA EXTRACTION: Data on study populations, echocardiographic criteria, and methodological quality of studies were extracted. DATA SYNTHESIS: Negative likelihood ratios, which indicate to what extent the posterior odds of left ventricular hypertrophy is reduced by a negative test, were calculated. RESULTS: 21 studies and data on 5608 patients were analysed. The median prevalence of left ventricular hypertrophy was 33% (interquartile range 23-41%) in primary care settings (10 studies) and 65% (37-81%) in secondary care settings (11 studies). The median negative likelihood ratio was similar across electrocardiographic indexes, ranging from 0.85 (range 0.34-1.03) for the Romhilt-Estes score (with threshold > or =4 points) to 0.91 (0.70-1.01) for the Gubner index. Using the Romhilt-Estes score in primary care, a negative electrocardiogram result would reduce the typical pre-test probability from 33% to 31%. In secondary care the typical pre-test probability of 65% would be reduced to 63%. CONCLUSION: Electrocardiographic criteria should not be used to rule out left ventricular hypertrophy in patients with hypertension. PMID- 17726092 TI - Global expression profiles from C57BL/6J and DBA/2J mouse lungs to determine aging-related genes. AB - This study identified gene expression profiles that provided evidence for genomic mechanisms underlying the pathophysiology of aging lung. Aging lungs from C57BL/6 (B6) and DBA/2 (D2) mouse strains differ in physiology and morphometry. Lungs were harvested from B6 mice at 2, 18, and 26 mo and from D2 mice at 2 and 18 mo of age. Purified RNA was subjected to oligonucleotide microarray analyses, and differential expression analyses were performed for comparison of various data sets. A significant majority of differentially expressed genes were upregulated with aging in both strains. Aging D2 lungs uniquely exhibited upregulation in stress-response genes including xenobiotic detoxification cascades. In contrast, aging B6 lungs showed downregulation of heat shock-response genes. Age-dependent downregulation of genes common to both B6 and D2 strains included several collagen genes (e.g., Col1a1 and Col3a1). There was a greater elastin gene (Eln) expression in D2 mice at 2 mo, and Eln was uniquely downregulated with age in this strain. The matrix metalloproteinase 14 gene (Mmp14), critical to alveolar structural integrity, was also downregulated with aging in D2 mice only. Several polymorphisms in the regulatory and untranslated regions of Mmp14 were identified between strains, suggesting that variation in Mmp14 gene regulation contributes to accelerated aging of lungs in D2 mice. In summary, lungs of B6 and D2 mice age with variable rates at the gene expression level, and these quantifiable genomic differences provide a template for understanding the variability in age-dependent changes in lung structure and function. PMID- 17726093 TI - Effect of the nonreducing end of Shigella dysenteriae type 1 O-specific oligosaccharides on their immunogenicity as conjugates in mice. AB - Endemic and epidemic shigellosis, an acute invasive disease of the lower intestines, afflicts millions of people worldwide with an estimated one million fatalities per annum at a low infectious dose. Our approach to vaccine development against Shigella is based on the hypothesis that serum IgG antibodies to the O-specific polysaccharide (O-SP) domains of the LPS of these organisms confer protection to infection. The synthetic oligosaccharides corresponding to the tetrasaccharide repeating unit of the O-SP of Shigella dysenteriae type 1 covalently linked to human serum albumin elicited O-SP-specific IgG in mice. The antibody levels were a function of both the saccharide chain length and their loading on the protein. These synthetic saccharide conjugates elicited significantly higher levels of IgG anti O-SP than conjugates prepared with the O SP from the bacteria. Here, we evaluated the influence of the nonreducing terminal monosaccharide on the serum antibody response. To this end, we prepared synthetic oligosaccharides comprising hexa- to tridecasaccharide fragments of the native O-SP, having one of the four monosaccharide residues that constitute the repeating unit at their termini and bound them to BSA by a single-point attachment. The conjugates contained an average of 19 saccharide chains per BSA. The synthetic oligosaccharides inhibited the binding of serum raised against whole bacteria to its LPS to a similar extent but lower than the native O-SP. The highest anti-LPS levels were elicited by conjugates having N-acetylglucosamine (10-mer) or galactose residues (7- and 11-mers) at their nonreducing termini. PMID- 17726094 TI - Enhanced subunit interactions with gemcitabine-5'-diphosphate inhibit ribonucleotide reductases. AB - Ribonucleotide reductases (RNRs) catalyze the conversion of nucleotides to deoxynucleotides in all organisms. The class I RNRs are composed of two subunits, alpha and beta, with proposed quaternary structures of alpha2beta2, alpha6beta2, or alpha6beta6, depending on the organism. The alpha subunits bind the nucleoside diphosphate substrates and the dNTP/ATP allosteric effectors that govern specificity and turnover. The beta2 subunit houses the diferric Y* (1 radical per beta2) cofactor that is required to initiate nucleotide reduction. 2',2'-difluoro 2'-deoxycytidine (F2C) is presently used clinically in a variety of cancer treatments and the 5'-diphosphorylated F2C (F2CDP) is a potent inhibitor of RNRs. The studies with [1'-(3)H]-F2CDP and [5-(3)H]-F2CDP have established that F2CDP is a substoichiometric mechanism based inhibitor (0.5 eq F2CDP/alpha) of both the Escherichia coli and the human RNRs in the presence of reductant. Inactivation is caused by covalent labeling of RNR by the sugar of F2CDP (0.5 eq/alpha) and is accompanied by release of 0.5 eq cytosine/alpha. Inactivation also results in loss of 40% of beta2 activity. Studies using size exclusion chromatography reveal that in the E. coli RNR, an alpha2beta2 tight complex is generated subsequent to enzyme inactivation by F2CDP, whereas in the human RNR, an alpha6beta6 tight complex is generated. Isolation of these complexes establishes that the weak interactions of the subunits in the absence of nucleotides are substantially increased in the presence of F2CDP and ATP. This information and the proposed asymmetry between the interactions of alphanbetan provide an explanation for complete inactivation of RNR with substoichiometric amounts of F2CDP. PMID- 17726095 TI - An inducible lambdoid prophage encoding cytolethal distending toxin (Cdt-I) and a type III effector protein in enteropathogenic Escherichia coli. AB - Cytolethal distending toxins (CDTs) are inhibitory cyclomodulins, which block eukaryotic cell proliferation and are produced by a diverse group of Gram negative bacteria, including Escherichia coli strains associated with intestinal and extraintestinal infections. However, the mode of transmission of the toxin gene clusters among diverse bacterial pathogens is unclear. We found that Cdt-I produced by enteropathogenic E. coli strains associated with diarrhea is encoded by a lambdoid prophage, which is inducible and infectious. The genome of Cdt-I converting phage (CDT-1Phi) comprises 47,021 nucleotides with 60 predicted ORFs organized into six genomic regions encoding the head and tail, virulence, integrase, unknown functions, regulation, and lysis. The genomic organization of CDT-1Phi is similar to those of SfV, a serotype-converting phage of Shigella flexneri, and UTI89, a prophage identified in uropathogenic E. coli. Besides the cdtI gene cluster, the virulence region of CDT-1Phi genome contains sequences homologous to a truncated cycle inhibiting factor and a type 3 effector protein. Mutation analysis of susceptible E. coli strain C600 suggested that the outer membrane protein OmpC is a putative receptor for CDT-1Phi. CDT-1Phi genome was also found to integrate into the host bacterial chromosome forming lysogens, which produced biologically active Cdt-I. Furthermore, phage induction appeared to cause enhanced toxigenicity of the E. coli strains carrying lysogenic CDT 1Phi. Our results suggest that CDT-1Phi is the latest member of a growing family of lambdoid phages encoding bacterial cyclomodulins and that the phage may have a role in horizontal transfer of these virulence genes. PMID- 17726096 TI - Phycobilin:cystein-84 biliprotein lyase, a near-universal lyase for cysteine-84 binding sites in cyanobacterial phycobiliproteins. AB - Phycobilisomes, the light-harvesting complexes of cyanobacteria and red algae, contain two to four types of chromophores that are attached covalently to seven or more members of a family of homologous proteins, each carrying one to four binding sites. Chromophore binding to apoproteins is catalyzed by lyases, of which only few have been characterized in detail. The situation is complicated by nonenzymatic background binding to some apoproteins. Using a modular multiplasmidic expression-reconstitution assay in Escherichia coli with low background binding, phycobilin:cystein-84 biliprotein lyase (CpeS1) from Anabaena PCC7120, has been characterized as a nearly universal lyase for the cysteine-84 binding site that is conserved in all biliproteins. It catalyzes covalent attachment of phycocyanobilin to all allophycocyanin subunits and to cysteine-84 in the beta-subunits of C-phycocyanin and phycoerythrocyanin. Together with the known lyases, it can thereby account for chromophore binding to all binding sites of the phycobiliproteins of Anabaena PCC7120. Moreover, it catalyzes the attachment of phycoerythrobilin to cysteine-84 of both subunits of C phycoerythrin. The only exceptions not served by CpeS1 among the cysteine-84 sites are the alpha-subunits from phycocyanin and phycoerythrocyanin, which, by sequence analyses, have been defined as members of a subclass that is served by the more specialized E/F type lyases. PMID- 17726097 TI - Solvent coarse-graining and the string method applied to the hydrophobic collapse of a hydrated chain. AB - With computer simulations of >100,000 atoms, the mechanism for the hydrophobic collapse of an idealized hydrated chain was obtained by tiling space with (0.2 nm)(3) cubes and projecting the atomistic water molecule positions onto this grid. With the coarse-grained field thus defined, the string method in collective variables was used to compute a minimum free-energy pathway (MFEP) for the collapsing chain. These calculations provide a proof of principle for a coarse grained description of water solvent. Furthermore, the calculated MFEP characterizes the mechanism for the collapse of the hydrated chain by providing a path of maximum likelihood for dynamical trajectories. The reliability of the calculated MFEP was confirmed with the use of conventional molecular dynamics trajectories. Analysis of the MFEP provides atomistic confirmation for the mechanism of hydrophobic collapse proposed by ten Wolde and Chandler. In particular, we show that length-scale-dependent hydrophobic dewetting is the rate limiting step in the hydrophobic collapse of the considered chain. PMID- 17726098 TI - Inhibitors of metabolism rescue cell death in Huntington's disease models. AB - Huntington's disease (HD) is a fatal inherited neurodegenerative disorder. HD is caused by polyglutamine expansions in the huntingtin (htt) protein that result in neuronal loss and contribute to HD pathology. The mechanisms of neuronal loss in HD are elusive, and there is no therapy to alleviate HD. To find small molecules that slow neuronal loss in HD, we screened 1,040 biologically active molecules to identify suppressors of cell death in a neuronal cell culture model of HD. We found that inhibitors of mitochondrial function or glycolysis rescued cell death in this cell culture and in in vivo HD models. These inhibitors prevented cell death by activating prosurvival ERK and AKT signaling but without altering cellular ATP levels. ERK and AKT inhibition through the use of specific chemical inhibitors abrogated the rescue, whereas their activation through the use of growth factors rescued cell death, suggesting that this activation could explain the protective effect of metabolic inhibitors. Both ERK and AKT signaling are disrupted in HD, and activating these pathways is protective in several HD models. Our results reveal a mechanism for activating prosurvival signaling that could be exploited for treating HD and possibly other neurodegenerative disorders. PMID- 17726099 TI - Tracing electronic pathways in molecules by using inelastic tunneling spectroscopy. AB - Using inelastic electron tunneling spectroscopy (IETS) to measure the vibronic structure of nonequilibrium molecular transport, aided by a quantitative interpretation scheme based on Green's function-density functional theory methods, we are able to characterize the actual pathways that the electrons traverse when moving through a molecule in a molecular transport junction. We show that the IETS observations directly index electron tunneling pathways along the given normal coordinates of the molecule. One can then interpret the maxima in the IETS spectrum in terms of the specific paths that the electrons follow as they traverse the molecular junction. Therefore, IETS measurements not only prove (by the appearance of molecular vibrational frequencies in the spectrum) that the tunneling charges, in fact, pass through the molecule, but also can be used to determine the transport pathways and how they change with the geometry and placement of molecules in junctions. PMID- 17726100 TI - Arabidopsis CYCD3 D-type cyclins link cell proliferation and endocycles and are rate-limiting for cytokinin responses. AB - Current understanding of the integration of cell division and expansion in the development of plant lateral organs such as leaves is limited. Cell number is established during a mitotic phase, and subsequent growth into a mature organ relies primarily on cell expansion accompanied by endocycles. Here we show that the three Arabidopsis cyclin D3 (CYCD3) genes are expressed in overlapping but distinct patterns in developing lateral organs and the shoot meristem. Triple loss-of-function mutants show that CYCD3 function is essential neither for the mitotic cell cycle nor for morphogenesis. Rather, analysis of mutant and reciprocal overexpression phenotypes shows that CYCD3 function contributes to the control of cell number in developing leaves by regulating the duration of the mitotic phase and timing of the transition to endocycles. Petals, which normally do not endoreduplicate, respond to loss of CYCD3 function with larger cells that initiate endocycles. The phytohormone cytokinin regulates cell division in the shoot meristem and developing leaves and induces CYCD3 expression. Loss of CYCD3 impairs shoot meristem function and leads to reduced cytokinin responses, including the inability to initiate shoots on callus, without affecting endogenous cytokinin levels. We conclude that CYCD3 activity is important for determining cell number in developing lateral organs and the relative contribution of the alternative processes of cell production and cell expansion to overall organ growth, as well as mediating cytokinin effects in apical growth and development. PMID- 17726101 TI - Breaking up the correlation between efficacy and toxicity for nonviral gene delivery. AB - Nonviral nucleic acid delivery to cells and tissues is considered a standard tool in life science research. However, although an ideal delivery system should have high efficacy and minimal toxicity, existing materials fall short, most of them being either too toxic or little effective. We hypothesized that disulfide cross linked low-molecular-weight (MW) linear poly(ethylene imine) (MW<4.6 kDa) would overcome this limitation. Investigations with these materials revealed that the extracellular high MW provided outstandingly high transfection efficacies (up to 69.62+/-4.18% in HEK cells). We confirmed that the intracellular reductive degradation produced mainly nontoxic fragments (cell survival 98.69+/-4.79%). When we compared the polymers in >1,400 individual experiments to seven commercial transfection reagents in seven different cell lines, we found highly superior transfection efficacies and substantially lower toxicities. This renders reductive degradation a highly promising tool for the design of new transfection materials. PMID- 17726102 TI - Automated de novo prediction of native-like RNA tertiary structures. AB - RNA tertiary structure prediction has been based almost entirely on base-pairing constraints derived from phylogenetic covariation analysis. We describe here a complementary approach, inspired by the Rosetta low-resolution protein structure prediction method, that seeks the lowest energy tertiary structure for a given RNA sequence without using evolutionary information. In a benchmark test of 20 RNA sequences with known structure and lengths of approximately 30 nt, the new method reproduces better than 90% of Watson-Crick base pairs, comparable with the accuracy of secondary structure prediction methods. In more than half the cases, at least one of the top five models agrees with the native structure to better than 4 A rmsd over the backbone. Most importantly, the method recapitulates more than one-third of non-Watson-Crick base pairs seen in the native structures. Tandem stacks of "sheared" base pairs, base triplets, and pseudoknots are among the noncanonical features reproduced in the models. In the cases in which none of the top five models were native-like, higher energy conformations similar to the native structures are still sampled frequently but not assigned low energies. These results suggest that modest improvements in the energy function, together with the incorporation of information from phylogenetic covariance, may allow confident and accurate structure prediction for larger and more complex RNA chains. PMID- 17726103 TI - Lsh controls Hox gene silencing during development. AB - Polycomb-mediated repression and DNA methylation are important epigenetic mechanisms of gene silencing. Recent evidence suggests a functional link between the polycomb repressive complex (PRC) and Dnmts in cancer cells. Here we provide evidence that Lsh, a regulator of DNA methylation, is also involved in normal control of PRC-mediated silencing during embryogenesis. We demonstrate that Lsh, a SNF2 homolog, can associate with some Hox genes and regulates Dnmt3b binding, DNA methylation, and silencing of Hox genes during development. Moreover, Lsh can associate with PRC1 components and influence PRC-mediated histone modifications. Thus Lsh is part of a physiological feedback loop that reinforces DNA methylation and silencing of PRC targets. PMID- 17726104 TI - Role of VEGF in maintaining renal structure and function under normotensive and hypertensive conditions. AB - Inhibiting the actions of VEGF is a new therapeutic paradigm in cancer management with antiangiogenic therapy also under intensive investigation in a range of nonmalignant diseases characterized by pathological angiogenesis. However, the effects of VEGF inhibition on organs that constitutively express it in adulthood, such as the kidney, are mostly unknown. Accordingly, we examined the effect of VEGF inhibition on renal structure and function under physiological conditions and in the setting of the common renal stressors: hypertension and activation of the renin-angiotensin system. When compared with normotensive Sprague-Dawley (SD) rats, glomerular VEGF mRNA was increased 2-fold in transgenic (mRen-2)27 rats that overexpress renin with spontaneously hypertensive rat (SHR) kidneys showing VEGF expression levels that were intermediate between them. Administration of either an orally active inhibitor of the type 2 VEGF receptor (VEGFR-2) tyrosine kinase or a VEGF neutralizing antibody to TGR(mRen-2)27 rats resulted in loss of glomerular endothelial cells and transformation to a malignant hypertensive phenotype with severe glomerulosclerosis. VEGFR-2 kinase inhibition treatment was well tolerated in SDs and SHRs; although even in these animals there was detectable endothelial cell loss and rise in albuminuria. Mild mesangial expansion was also noted in hypertensive SHR, but not in SD rats. These studies illustrate: (i) VEGF has a role in the maintenance of glomerular endothelial integrity under physiological circumstances, (ii) glomerular VEGF is increased in response to hypertension and activation of the renin-angiotensin system, and (iii) VEGF signaling plays a protective role in the setting of these renal stressors. PMID- 17726106 TI - T cell activation requires mitochondrial translocation to the immunological synapse. AB - T helper (Th) cell activation is required for the adaptive immune response. Formation of the immunological synapse (IS) between Th cells and antigen presenting cells is essential for Th cell activation. IS formation induces the polarization and redistribution of many signaling molecules; however, very little is known about organelle redistribution during IS formation in Th cells. We show that formation of the IS induced cytoskeleton-dependent mitochondrial redistribution to the immediate vicinity of the IS. Using total internal reflection microscopy, we found that upon stimulation, the distance between the IS and mitochondria was decreased to values<200 nm. Consequently, mitochondria close to the IS took up more Ca2+ than the ones farther away from the IS. The redistribution of mitochondria to the IS was necessary to maintain Ca2+ influx across the plasma membrane and Ca2+-dependent Th cell activation. Our results suggest that mitochondria are part of the signaling complex at the IS and that their localization close to the IS is required for Th cell activation. PMID- 17726105 TI - ALL1 fusion proteins induce deregulation of EphA7 and ERK phosphorylation in human acute leukemias. AB - Erythropoietin-producing hepatoma-amplified sequence (Eph) receptor tyrosine kinases and their cell-surface-bound ligands, the ephrins, function as a unique signaling system triggered by cell-to-cell interaction and have been shown to mediate neurodevelopmental processes. In addition, recent studies showed deregulation of some of Eph/ephrin genes in human malignancies, suggesting the involvement of this signaling pathway in tumorigenesis. The ALL1 (also termed MLL) gene on human chromosome 11q23 was isolated by virtue of its involvement in recurrent chromosome translocations associated with acute leukemias with poor prognosis. The translocations fuse ALL1 to any of >50 partner genes and result in production of chimeric proteins composed of the ALL1 N terminus and the C terminus of the partner protein. The most common translocations in ALL1 associated leukemias are t(4;11) and t(9;11), which generate ALL1/AF4 and ALL1/AF9 fusion protein, respectively. In the present study, we sought to determine whether ALL1 fusion proteins are involved in regulation of Eph/ephrin genes. Screening of K562 cells producing recombinant ALL1/AF4 or ALL1/AF9 fusion protein revealed transcriptional up-regulation of the EphA7. Consistent with this finding, siRNA-mediated suppression of ALL1/AF4 in SEMK2 cells carrying the t(4;11) chromosome translocation resulted in down-regulation of EphA7. ChIP analysis demonstrated the occupancy of tagged ALL1 fusion proteins on the EphA7 promoter, pointing to EphA7 as a direct target of the formers. Further studies demonstrate that EphA7 up-regulation is accompanied by ERK phosphorylation. Finally, we show apoptotic cell death, specific for leukemic cells carrying the t(4;11) chromosome translocation, after treatment of the cells with an ERK phosphorylation blocker. PMID- 17726107 TI - Conformational instability of the MARK3 UBA domain compromises ubiquitin recognition and promotes interaction with the adjacent kinase domain. AB - The Par-1/MARK protein kinases play a pivotal role in establishing cellular polarity. This family of kinases contains a unique domain architecture, in which a ubiquitin-associated (UBA) domain is located C-terminal to the kinase domain. We have used a combination of x-ray crystallography and NMR dynamics experiments to understand the interaction of the human (h) MARK3 UBA domain with the adjacent kinase domain as compared with ubiquitin. The x-ray crystal structure of the linked hMARK3 kinase and UBA domains establishes that the UBA domain forms a stable intramolecular interaction with the N-terminal lobe of the kinase domain. However, solution-state NMR studies of the isolated UBA domain indicate that it is highly dynamic, undergoing conformational transitions that can be explained by a folding-unfolding equilibrium. NMR titration experiments indicated that the hMARK3 UBA domain has a detectable but extremely weak affinity for mono ubiquitin, which suggests that conformational instability of the isolated hMARK3 UBA domain attenuates binding to ubiquitin despite the presence of residues typically involved in ubiquitin recognition. Our data identify a molecular mechanism through which the hMARK3 UBA domain has evolved to bind the kinase domain, in a fashion that stabilizes an open conformation of the N- and C terminal lobes, at the expense of its capacity to engage ubiquitin. These results may be relevant more generally to the 30% of UBA domains that lack significant ubiquitin-binding activity, and they suggest a unique mechanism by which interaction domains may evolve new binding properties. PMID- 17726108 TI - CD200 and its receptor, CD200R, modulate bone mass via the differentiation of osteoclasts. AB - Fusion of macrophages is an essential step in the differentiation of osteoclasts, which play a central role in the development and remodeling of bone. Osteoclasts are important mediators of bone loss, which leads, for example, to osteoporosis. Macrophage fusion receptor/signal regulatory protein alpha (MFR/SIRPalpha) and its ligand CD47, which are members of the Ig superfamily (IgSF), have been implicated in the fusion of macrophages. We show that CD200, which is not expressed in cells that belong to the myeloid lineage, is strongly expressed in macrophages at the onset of fusion. By contrast, the CD200 receptor (CD200R), which, like CD200, belongs to the IgSF, is expressed only in cells that belong to the myeloid lineage, including osteoclasts, and in CD4+ T cells. Osteoclasts from CD200-/- mice differentiated at a reduced rate. Activation of the NF-kappaB and MAP kinase signaling pathways downstream of RANK, a receptor that plays a central role in the differentiation of osteoclasts, was depressed in these cells. A soluble recombinant protein that included the extracellular domain of CD200 rescued the fusion of CD200-/- macrophages and their activation downstream of RANK. Conversely, addition of a soluble recombinant protein that included the extracellular domain of CD200R or short-hairpin RNA-mediated silencing of the expression of CD200R prevented fusion. Thus CD200 engagement of the CD200R at the initiation of macrophage fusion regulated further differentiation to osteoclasts. Consistent with in vitro observations, CD200-/- mice contained fewer osteoclasts and accumulated more bone than CD200+/+ mice. The CD200-CD200R axis is therefore a putative regulator of bone mass, via the formation of osteoclasts. PMID- 17726109 TI - Gamma oscillations dynamically couple hippocampal CA3 and CA1 regions during memory task performance. AB - The hippocampal formation is believed to be critical for the encoding, consolidation, and retrieval of episodic memories. Yet, how these processes are supported by the anatomically diverse hippocampal networks is still unknown. To examine this issue, we tested rats in a hippocampus-dependent delayed spatial alternation task on a modified T maze while simultaneously recording local field potentials from dendritic and somatic layers of the dentate gyrus, CA3, and CA1 regions by using high-density, 96-site silicon probes. Both the power and coherence of gamma oscillations exhibited layer-specific changes during task performance. Peak increases in the gamma power and coherence were found in the CA3-CA1 interface on the maze segment approaching the T junction, independent of motor aspects of task performance. These results show that hippocampal networks can be dynamically coupled by gamma oscillations according to specific behavioral demands. Based on these findings, we propose that gamma oscillations may serve as a physiological mechanism by which CA3 output can coordinate CA1 activity to support retrieval of hippocampus-dependent memories. PMID- 17726110 TI - Galphai generates multiple Pins activation states to link cortical polarity and spindle orientation in Drosophila neuroblasts. AB - Drosophila neuroblasts divide asymmetrically by aligning their mitotic spindle with cortical cell polarity to generate distinct sibling cell types. Neuroblasts asymmetrically localize Galphai, Pins, and Mud proteins; Pins/Galphai direct cortical polarity, whereas Mud is required for spindle orientation. It is currently unknown how Galphai-Pins-Mud binding is regulated to link cortical polarity with spindle orientation. Here, we show that Pins forms a "closed" state via intramolecular GoLoco-tetratricopeptide repeat (TPR) interactions, which regulate Mud binding. Biochemical, genetic, and live imaging experiments show that Galphai binds to the first of three Pins GoLoco motifs to recruit Pins to the apical cortex without "opening" Pins or recruiting Mud. However, Galphai and Mud bind cooperatively to the Pins GoLocos 2/3 and tetratricopeptide repeat domains, respectively, thereby restricting Pins-Mud interaction to the apical cortex and fixing spindle orientation. We conclude that Pins has multiple activity states that generate cortical polarity and link it with mitotic spindle orientation. PMID- 17726111 TI - A cyclic nucleotide-gated channel is essential for polarized tip growth of pollen. AB - Ion signals are critical to regulating polarized growth in many cell types, including pollen in plants and neurons in animals. Genetic evidence presented here indicates that pollen tube growth requires cyclic nucleotide-gated channel (CNGC) 18. CNGCs are nonspecific cation channels found in plants and animals and have well established functions in excitatory signal transduction events in animals. In Arabidopsis, male sterility was observed for two cngc18 null mutations. CNGC18 is expressed primarily in pollen, as indicated from a promoter::GUS (beta-glucuronidase) reporter analysis and expression profiling. The underlying cause of sterility was identified as a defect in pollen tube growth, resulting in tubes that were kinky, short, often thin, and unable to grow into the transmitting tract. Expression of a GFP-tagged CNGC18 in mutant pollen provided complementation and evidence for asymmetric localization of CNGC18 to the plasma membrane at the growing tip, starting at the time of pollen grain germination. Heterologous expression of CNGC18 in Escherichia coli resulted in a time- and concentration-dependent accumulation of more Ca2+. Thus, CNGC18 provides a mechanism to directly transduce a cyclic nucleotide (cNMP) signal into an ion flux that can produce a localized signal capable of regulating the pollen tip-growth machinery. These results identify a CNGC that is essential to an organism's life cycle and raise the possibility that CNGCs have a widespread role in regulating cell-growth dynamics in both plant and animals. PMID- 17726112 TI - Essential role for autophagy protein Atg7 in the maintenance of axonal homeostasis and the prevention of axonal degeneration. AB - Autophagy is a regulated lysosomal degradation process that involves autophagosome formation and transport. Although recent evidence indicates that basal levels of autophagy protect against neurodegeneration, the exact mechanism whereby this occurs is not known. By using conditional knockout mutant mice, we report that neuronal autophagy is particularly important for the maintenance of local homeostasis of axon terminals and protection against axonal degeneration. We show that specific ablation of an essential autophagy gene, Atg7, in Purkinje cells initially causes cell-autonomous, progressive dystrophy (manifested by axonal swellings) and degeneration of the axon terminals. Consistent with suppression of autophagy, no autophagosomes are observed in these dystrophic swellings, which is in contrast to accumulation of autophagosomes in the axonal dystrophic swellings under pathological conditions. Axonal dystrophy of mutant Purkinje cells proceeds with little sign of dendritic or spine atrophy, indicating that axon terminals are much more vulnerable to autophagy impairment than dendrites. This early pathological event in the axons is followed by cell autonomous Purkinje cell death and mouse behavioral deficits. Furthermore, ultrastructural analyses of mutant Purkinje cells reveal an accumulation of aberrant membrane structures in the axonal dystrophic swellings. Finally, we observe double-membrane vacuole-like structures in wild-type Purkinje cell axons, whereas these structures are abolished in mutant Purkinje cell axons. Thus, we conclude that the autophagy protein Atg7 is required for membrane trafficking and turnover in the axons. Our study implicates impairment of axonal autophagy as a possible mechanism for axonopathy associated with neurodegeneration. PMID- 17726113 TI - Inhibition of the leucine-rich repeat protein LINGO-1 enhances survival, structure, and function of dopaminergic neurons in Parkinson's disease models. AB - The nervous system-specific leucine-rich repeat Ig-containing protein LINGO-1 is associated with the Nogo-66 receptor complex and is endowed with a canonical EGF receptor (EGFR)-like tyrosine phosphorylation site. Our studies indicate that LINGO-1 expression is elevated in the substantia nigra of Parkinson's disease (PD) patients compared with age-matched controls and in animal models of PD after neurotoxic lesions. LINGO-1 expression is present in midbrain dopaminergic (DA) neurons in the human and rodent brain. Therefore, the role of LINGO-1 in cell damage responses of DA neurons was examined in vitro and in experimental models of PD induced by either oxidative (6-hydroxydopamine) or mitochondrial (N-methyl 4-phenyl-1,2,3,6-tetrahydropyridine) toxicity. In LINGO-1 knockout mice, DA neuron survival was increased and behavioral abnormalities were reduced compared with WT. This neuroprotection was accompanied by increased Akt phosphorylation (p Akt). Similar neuroprotective in vivo effects on midbrain DA neurons were obtained in WT mice by blocking LINGO-1 activity using LINGO-1-Fc protein. Neuroprotection and enhanced neurite growth were also demonstrated for midbrain DA neurons in vitro. LINGO-1 antagonists (LINGO-1-Fc, dominant negative LINGO-1, and anti-LINGO-1 antibody) improved DA neuron survival in response to MPP+ in part by mechanisms that involve activation of the EGFR/Akt signaling pathway through a direct inhibition of LINGO-1's binding to EGFR. These results show that inhibitory agents of LINGO-1 activity can protect DA neurons against degeneration and indicate a role for the leucine-rich repeat protein LINGO-1 and related classes of proteins in the pathophysiological responses of midbrain DA neurons in PD. PMID- 17726114 TI - Molecular evidence of Late Archean archaea and the presence of a subsurface hydrothermal biosphere. AB - Highly cracked and isomerized archaeal lipids and bacterial lipids, structurally changed by thermal stress, are present in solvent extracts of 2,707- to 2,685 million-year-old (Ma) metasedimentary rocks from Timmins, ON, Canada. These lipids appear in conventional gas chromatograms as unresolved complex mixtures and include cyclic and acyclic biphytanes, C36-C39 derivatives of the biphytanes, and C31-C35 extended hopanes. Biphytane and extended hopanes are also found in high-pressure catalytic hydrogenation products released from solvent-extracted sediments, indicating that archaea and bacteria were present in Late Archean sedimentary environments. Postdepositional, hydrothermal gold mineralization and graphite precipitation occurred before metamorphism (approximately 2,665 Ma). Late Archean metamorphism significantly reduced the kerogen's adsorptive capacity and severely restricted sediment porosity, limiting the potential for post Archean additions of organic matter to the samples. Argillites exposed to hydrothermal gold mineralization have disproportionately high concentrations of extractable archaeal and bacterial lipids relative to what is releasable from their respective high-pressure catalytic hydrogenation product and what is observed for argillites deposited away from these hydrothermal settings. The addition of these lipids to the sediments likely results from a Late Archean subsurface hydrothermal biosphere of archaea and bacteria. PMID- 17726122 TI - The need for emergency medicine resident training in informed consent for procedures. AB - OBJECTIVES: To determine emergency medicine (EM) residents' perceptions and reported practices of obtaining informed consent for emergency department procedures. METHODS: The authors performed a cross-sectional observational study of EM residents. A brief, short-answer survey was distributed that covered the following topics related to informed consent: training, confidence and comfort levels, and current practices. Data were analyzed using basic frequency displays, and descriptive statistics are reported. RESULTS: Of the 20 programs contacted, 16 responded and agreed to distribute the invitation to their residents. A total of 402 of 490 eligible residents (82%) in the participating programs responded. The majority of EM residents (56%) had never received formal training on obtaining informed consent, and those who had reported that their primary exposure to formal training occurred during their medical school years (79%). More than half of the residents (56%) have felt uncomfortable obtaining consent for a procedure. Few residents (32%) felt very confident that they provide comprehensive information to patients, while 9% were not very confident that they disclose all pertinent risks, benefits, and alternatives to their patients. Sixty three percent of all EM residents believed formal training is necessary, and half (52%) reported interest in receiving training (i.e., listings of risks, benefits, and alternatives as well as standards for determining which procedures need consent). The residents' current perceptions of consent requirements for commonly performed emergency department procedures (emergent and nonemergent) are also reported. CONCLUSIONS: Few residents have had formal training in informed consent, and there is wide variability in the perception of which procedures require informed consent. Residents are not confident in their knowledge of all risks and benefits of common procedures, and comfort levels in obtaining informed consent are low. Residents can benefit from additional resources that provide standardized information and formal training on the issue. PMID- 17726123 TI - Progression of emergency medicine resident productivity. AB - OBJECTIVES: To evaluate the progression in productivity of emergency medicine (EM) residents by postgraduate year, as measured by hourly work in relative value units (RVUs). METHODS: This retrospective study was conducted at an Accreditation Council for Graduate Medical Education (ACGME)-accredited EM residency with a postgraduate year (PGY) 1-2-3 configuration. A query of an electronic billing database composed of more than 230,000 visits from academic years July 2003 to December 2006, representing at least four classes at each PGY level, was conducted. The main outcome was change in productivity in RVUs generated per hour, compared by resident PGY level. This measure encompasses not only volume of patients seen but also patient acuity in terms of evaluation and management services and procedures provided and supported by documentation adequate for coding. Descriptive statistics and Tukey's test were used for data analysis. RESULTS: Over the three-year study period, 70 EM residents were assessed at various levels of training. Productivity, as measured by mean RVUs generated per hour, was 2.51 (95% confidence interval [CI] = 2.20 to 2.82) for PGY-1 residents, 3.51 (95% CI = 3.12 to 3.90) for PGY-2 residents, and 3.61 (95% CI = 3.41 to 3.80) for PGY-3 residents (p < 0.001). Patient acuity (RVUs generated per patient) increased 5%-8% with each PGY progression: 3.05 (95% CI = 2.96 to 3.13) for PGY-1, 3.20 (95% CI = 3.09 to 3.31) for PGY-2, and 3.46 (95% CI = 3.42 to 3.50) for PGY-3 (p < 0.001). There was a statistically significant increase in productivity (p < 0.001) and acuity (p = 0.03) from PGY-1 to PGY-2, with acuity also increasing between PGY-2 and PGY-3 (p < 0.001). CONCLUSIONS: Hourly work productivity and acuity increased with experience within this ACGME-accredited EM residency. The progression in workload and acuity by PGY is measurable and commensurate with the graduated level of responsibility desired in an EM program. PMID- 17726124 TI - Modeling complex systems: gaining valid insights and avoiding mathematical delusions. PMID- 17726126 TI - Advanced statistics: developing a formal model of emergency department census and defining operational efficiency. AB - BACKGROUND: Emergency department (ED) crowding has been a frequent topic of investigation, but it is a concept without an objective definition. This has limited the scope of research and progress toward the development of consistent and meaningful operational responses. OBJECTIVES: To develop a straightforward model of ED census that incorporates concepts of ED crowding, daily patient surge, throughput time, and operational efficiency. METHODS: Using 2005-2006 patient encounter data at a Level 1 urban trauma center, a set of three stylized facts describing daily patterns of ED census was observed. These facts guided the development of a formal, mathematical model of ED census. Using this model, a metric of ED operational efficiency and a forecast of ED census were developed. RESULTS: The three stylized facts of daily ED census were 1) ED census is cyclical, 2) ED census exhibits an input-output relationship, and 3) unexpected shocks have long-lasting effects. These were represented by a three-equation system. This system was solved for the following expression, Census(t) = A(.) + B(.) cos(vT + epsilon) + a(e(t)), that captured the time path of ED census. Using nonlinear estimation, the parameters of this expression were estimated and a forecasting tool was developed. CONCLUSIONS: The basic pattern of ED census can be represented by a straightforward expression. This expression can be quickly adapted to a variety of inquiries regarding ED crowding, daily surge, and operational efficiency. PMID- 17726127 TI - Suicidal behavior in children younger than twelve: a diagnostic challenge for emergency department personnel. AB - Suicide is one of the leading causes of death in children younger than 12 years and is the fourth leading cause of death in 12 year olds. Increasing numbers of young children now present to the emergency department (ED) with mental health issues, and ED personnel must determine the most appropriate disposition options for these children, sometimes without the assistance of specialty mental health services. Much of the present body of literature describing suicidality fails to separate children from adolescents for analysis and discussion. This article reviews relevant literature pertaining to suicidal thoughts and behaviors in young children and discusses problems with available data, as well as epidemiology, risk factors, typical motivations, methods, assessment, and disposition for these patients. Suicidal children younger than 12 years are often clinically different from suicidal adolescents and adults and may require unique assessment and disposition strategies in the ED. A child who has ideation without a clear plan, or has made an attempt of low lethality, can sometimes be discharged home, provided that a supportive, responsible caregiver is willing to monitor the child and take him or her to outpatient mental health appointments. If the home environment is detrimental, or the child has used a method of high potential lethality, inpatient treatment is the most appropriate course of action. Mental health specialty services, when available, should be used to help determine the most appropriate disposition. PMID- 17726128 TI - Clinicopathological conference: 29-year-old with visual loss, hypertension, and a seizure. PMID- 17726129 TI - First death. PMID- 17726130 TI - Spectator sport: observing a pediatric resuscitation. PMID- 17726131 TI - Additional reflections about "first death". PMID- 17726132 TI - Emergency medicine in Iran, past and present. PMID- 17726133 TI - Comment on: Hosagai et al. (2007) Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation: Diabetes 56:901-911. PMID- 17726134 TI - Comment on: Harmancey et al. (2007) Adrenomedullin inhibits adipogenesis under transcriptional control of insulin: Diabetes 56:553-563. PMID- 17726135 TI - Comment on: Marchand and Polychronakos (2007) Evaluation of polymorphic splicing in the mechanism of the association of the insulin gene with diabetes: Diabetes 56:709-713. PMID- 17726137 TI - Enhanced survival and cure of F98 glioma-bearing rats following intracerebral delivery of carboplatin in combination with photon irradiation. AB - PURPOSE: The goal of the present study was to evaluate the efficacy of intracerebral (i.c.) administration of carboplatin by means of convection enhanced delivery (CED) in combination with fractionated, external beam photon irradiation for the treatment of F98 glioma-bearing rats. EXPERIMENTAL DESIGN: Carboplatin (20 microg/20 microL) was administrated i.c. by CED to F98 glioma bearing rats, 13 days after stereotactic implantation of 10(3) tumor cells. One day following initiation of CED, a 24-Gy X-ray dose was administered in three daily fractions of 8 Gy each. Photon irradiation was carried out using either a conventional (6 MV) linear accelerator or a monochromatic synchrotron source (80 keV) at the European Synchrotron Radiation Facility. The primary end point of this study was overall survival. RESULTS: The median survival times were 79 and 60 days and the corresponding percent increase in life spans were 182% and 114%, respectively, for the combination of carboplatin chemotherapy and irradiation with either 6-MV or 80-keV photons. A subset of long-term survivors (>200 days) were observed in both chemoradiotherapy groups: 16.6% and 8.3% for 6 MV and 80 keV, respectively. In contrast, the median survival times for 6-MV or 80-keV irradiated controls, chemotherapy alone, and untreated controls were 42, 51, 45, and 28 days, respectively. CONCLUSIONS: Our results convincingly show the therapeutic efficacy of i.c. administration of carboplatin by means of CED in combination with either 6-MV or 80-keV photons. Further studies are warranted to optimize this combination of chemoradiotherapy for malignant gliomas. PMID- 17726139 TI - Accuracy of colorectal polyp self-reports: findings from the colon cancer family registry. AB - INTRODUCTION: Colorectal adenomas and other types of polyps are commonly used as end points or risk factors in epidemiologic studies. However, it is not known how accurately patients are able to self-report the presence or absence of adenomas following colonoscopy. METHODS: Participants in the Colon Cancer Family Registry provided self-reports of recent colorectal cancer (CRC) screening activity, and whether or not they had ever been told they had a polyp. Positive and negative predictive values for polyp self-report were calculated by comparing medical records with self-reports from 488 participants. RESULTS: The positive predictive value for self-reported polyp was 80.9%, and the negative predictive value was 85.8%. The predictive values did not differ by age group or sex, but participants with a previous diagnosis of CRC had a lower negative predictive value (76.2%) than participants with no personal history of CRC (89.0%; P = 0.04). CONCLUSIONS: Predictive values for self-reports of polyps are fairly high, but researchers needing accurate polyp data should obtain medical record confirmation. Pursuing medical records on only those participants self-reporting a polyp could result in an underestimation of the polyp prevalence in a study population. PMID- 17726138 TI - Genetic variability in iron-related oxidative stress pathways (Nrf2, NQ01, NOS3, and HO-1), iron intake, and risk of postmenopausal breast cancer. AB - Oxidative stress resulting from excess reactive oxygen species and/or deficiencies in antioxidant capabilities may play a role in breast cancer etiology. In a nested case-control study of postmenopausal women (505 cases and 502 controls) from the American Cancer Society Prevention II Nutrition Cohort, we examined relationships between breast cancer risk and genetic polymorphisms of enzymes involved in the generation and removal of iron-mediated reactive oxygen species. Using unconditional logistic regression, genetic variations in Nrf2 (11108C>T), NQO1 (609C>T), NOS3 (894G>T), and HO-1 [(GT)(n) dinucleotide length polymorphism] were not associated with breast cancer risk in a multivariate model. A significant dose trend (P trend = 0.04), however, was observed for total number of putative "at-risk" alleles (Nrf T, NQO1 T, NOS T, and HO-1 LL and LM genotypes), with those carrying three or more at-risk alleles having an odds ratio (OR) of 1.56 [95% confidence interval (95% CI), 0.97-2.51] compared with those having none. When examined in relation to iron, carriage of three or more high-risk alleles in the highest tertile of iron intake (OR, 2.27; 95% CI, 0.97 5.29; P trend = 0.02; P interaction = 0.30) or among users of supplemental iron (OR, 2.39; 95% CI, 1.09-5.26; P trend = 0.02; P interaction = 0.11) resulted in a greater than 2-fold increased risk compared with women with no high-risk alleles. Increased risk was also observed among supplement users with the HO-1 LL or LM genotypes (OR, 1.56; 95% CI, 1.01-2.41; P interaction = 0.32) compared with S allele carriers and MM genotypes combined. These results indicate that women with genotypes resulting in potentially higher levels of iron-generated oxidative stress may be at increased risk of breast cancer and that this association may be most relevant among women with high iron intake. PMID- 17726141 TI - Glyceroneogenesis and the supply of glycerol-3-phosphate for glyceride-glycerol synthesis in liver slices of fasted and diabetic rats. AB - The pathways of glycerol-3-phosphate (G3P) generation for glyceride synthesis were examined in precision-cut liver slices of fasted and diabetic rats. The incorporation of 5 mM [U-(14)C]glucose into glyceride-glycerol, used to evaluate G3P generation via glycolysis, was reduced by approximately 26-36% in liver slices of fasted and diabetic rats. The glycolytic flux was reduced by approximately 60% in both groups. The incorporation of 1.0 mM [2-(14)C]pyruvate into glyceride-glycerol (glyceroneogenesis) increased approximately 50% and approximately 36% in slices of fasted and diabetic rats, respectively, which also showed a two-fold increase in the activity phosphoenolpyruvate carboxykinase. The increased incorporation of 1.0 mM [2-(14)C]pyruvate into glyceride-glycerol by slices of fasted rats was not affected by the addition of 5 mM glucose to the incubation medium. The activity of glycerokinase and the incorporation of 1 mM [U (14)C]glycerol into glyceride-glycerol, evaluators of G3P formation by direct glycerol phosphorylation, did not differ significantly from controls in slices of the two experimental groups. Rates of incorporation of 1 mM [2-(14)C]pyruvate and [U-(14)C]glycerol into glucose of incubation medium (gluconeogenesis) were approximately 140 and approximately 20% higher in fasted and diabetic slices than in control slices. It could be estimated that glyceroneogenesis by liver slices of fasted rats contributed with approximately 20% of G3P generated for glyceride glycerol synthesis, the glycolytic pathway with approximately 5%, and direct phosphorylation of glycerol by glycerokinase with approximately 75%. Pyruvate contributed with 54% and glycerol with 46% of gluconeogenesis. The present data indicate that glyceroneogenesis has a significant participation in the generation of G3P needed for the increased glyceride-glycerol synthesis in liver during fasting and diabetes. PMID- 17726140 TI - Novel role of the anorexigenic peptide neuromedin U in the control of LH secretion and its regulation by gonadal hormones and photoperiod. AB - Neuromedin U (NMU) is a widely spread neuropeptide, with predominant expression at the gastrointestinal tract and brain, putatively involved in the regulation of a diversity of biological functions, including food intake, energy balance and circadian rhythms; all closely related to reproduction. Yet, the implication of NMU in the control of the gonadotropic axis remains scarcely studied. We report herein analyses on the hypothalamic expression and function of NMU in different physiological and experimental states of the rat reproductive system. Expression of NMU mRNA at the hypothalamus was persistently detected along female postnatal development, with maximum levels in adulthood that fluctuated across the cycle and were modulated by ovarian steroids. Acute central administration of NMU evoked increases of serum LH levels in pubertal female rats, while repeated injection of NMU tended to advance vaginal opening. Likewise, central injection of NMU increased serum LH concentrations in cycling female rats, with peak responses in estrus. In contrast, NMU significantly inhibited preelevated LH secretion in gonadectomized and kisspeptin-treated rats. Finally, in noncycling females due to photoperiodic manipulation (constant light), hypothalamic NMU mRNA levels were markedly depressed, but relative LH responses to exogenous NMU were significantly augmented. All together, our present data support a predominant stimulatory role of NMU in the control of the female gonadotropic axis, which appears under the influence of developmental, hormonal, and photoperiodic cues, and might contribute to the joint regulation of energy balance, biological rhythms, and reproduction. PMID- 17726142 TI - Measurement of pancreatic islet cell proliferation by heavy water labeling. AB - We describe a sensitive technique for measuring long-term islet cell proliferation rates in vivo in rats. Pancreatic islets were isolated and the incorporation of deuterium ((2)H) from heavy water ((2)H(2)O) into the deoxyribose moiety of DNA was measured by GC-MS. The results of heavy water labeling and BrdU staining were compared. The two methods were highly correlated (r = 0.9581, P < 0.001). Based on long-term heavy water labeling, approximately 50% of islet cells divided in rats between 8 and 15 wk of age. Of interest, long term BrdU administration suppressed proliferation of islet cells significantly, but not of bone marrow cells. Physiological evidence further supported the validity of the method: older animals (24 wk old) had 60% lower islet cell proliferation rates than younger rats (5 wk old), and partial (50%) pancreatectomy increased proliferation by 20%. In addition, cholecystokinin-8 treatment significantly stimulated proliferation in pancreatectomized rats only. In summary, heavy water labeling is a quantitative approach for measuring islet cell proliferation and testing therapeutic agents. PMID- 17726143 TI - Knockdown of clock genes in the suprachiasmatic nucleus blocks prolactin surges and alters FRA expression in the locus coeruleus of female rats. AB - The nature of the circadian signal from the suprachiasmatic nucleus (SCN) required for prolactin (PRL) surges is unknown. Because the SCN neuronal circadian rhythm is determined by a feedback loop of Period (Per) 1, Per2, and circadian locomotor output cycles kaput (Clock) gene expressions, we investigated the effect of SCN rhythmicity on PRL surges by disrupting this loop. Because lesion of the locus coeruleus (LC) abolishes PRL surges and these neurons receive SCN projections, we investigated the role of SCN rhythmicity in the LC neuronal circadian rhythm as a possible component of the circadian mechanism regulating PRL surges. Cycling rats on proestrous day and estradiol-treated ovariectomized rats received injections of antisense or random-sequence deoxyoligonucleotide cocktails for clock genes (Per1, Per2, and Clock) in the SCN, and blood samples were taken for PRL measurements. The percentage of tyrosine hydroxylase-positive neurons immunoreactive to Fos-related antigen (FRA) was determined in ovariectomized rats submitted to the cocktail injections and in a 12:12-h light:dark (LD) or constant dark (DD) environment. The antisense cocktail abolished both the proestrous and the estradiol-induced PRL surges observed in the afternoon and the increase of FRA expression in the LC neurons at Zeitgeber time 14 in LD and at circadian time 14 in DD. Because SCN afferents and efferents were probably preserved, the SCN rhythmicity is essential for the magnitude of daily PRL surges in female rats as well as for LC neuronal circadian rhythm. SCN neurons therefore determine PRL secretory surges, possibly by modulating LC circadian neuronal activity. PMID- 17726144 TI - Activity and expression of different members of the caspase family in the rat corpus luteum during pregnancy and postpartum. AB - Studies were designed to examine the expression and activity of four caspases that contribute to the initial (caspases-2, -8, and -9) and final (caspase-3) events in apoptosis in the rat corpus luteum (CL) during pregnancy (days 7, 17, 19, and 21 of gestation), postpartum (days 1 and 4), and after injection (0, 8, 16, 24, and 36 h) of the physiological luteolysin PGF2alpha. In addition, the temporal relationship of caspase expression/activity relative to steroid production and luteal regression was evaluated. During pregnancy, the activity of all four caspases was significantly greater on day 19, before a decline in CL progesterone (P) and CYP11A1 levels at day 21 of gestation. The levels of the caspase-3 active fragment (p17, measured by Western blot) also increased at days 19 and 21 of pregnancy. Immunohistochemical analyses detected specific staining for the caspases in luteal cells (large and small) as well as in endothelial cells. However, the percentage of apoptotic cells did not increase in the CL until postpartum. Following PGF2alpha injection, there was a significant decrease in CL P by 24 h, although the activity of all four caspases did not increase until 36 h posttreatment. The active p17 fragment of caspase-3 also significantly increased at 36 h post-PGF2alpha. These results suggest that an increase in the activity of caspases-2, -8, -9, and -3 is associated with the early events of natural luteolysis at the end of pregnancy. Also, the exogenous administration of the luteolysin PGF2alpha may regulate members of the caspase family. PMID- 17726145 TI - Influence of preconditioning-like hypoxia on the liver of developing methyl deficient rats. AB - Deficiency in nutritional determinants of homocysteine (HCY) metabolism, such as vitamin B(12) and folate, during pregnancy is known to influence HCY levels in the progeny, which in turn may exert adverse effects during development, including liver defects. Since short hypoxia has been shown to induce tolerance to subsequent stress in various cells including hepatocytes, and as vitamins B deficiency and hypoxic episodes may simultaneously occur in neonates, we aimed to investigate the influence of brief postnatal hypoxia (100% N(2) for 5 min) on the liver of rat pups born from dams fed a deficient regimen, i.e., depleted in vitamins B(12), B(2), folate, and choline. Four experimental groups were studied: control, hypoxia, deficiency, and hypoxia + deficiency. Although hypoxia transiently stimulated HCY catabolic pathways, it was associated with a progressive increase of hyperhomocysteinemia in deficient pups, with a fall of cystathionine beta-synthase activity at 21 days. At this stage, inducible NO synthase activity was dramatically increased and glutathione reductase decreased, specifically in the group combining hypoxia and deficiency. Also, hypoxia enhanced the deficiency-induced drop of the S-adenosylmethionine/S adenosylhomocysteine ratio. In parallel, early exposure to the methyl-deficient regimen induced oxidative stress and led to hepatic steatosis, which was found to be more severe in pups additionally exposed to hypoxia. In conclusion, brief neonatal hypoxia may accentuate the long-term adverse effects of impaired HCY metabolism in the liver resulting from an inadequate nutritional regimen during pregnancy, and our data emphasize the importance of early factors on adult disease. PMID- 17726146 TI - Selective PPARdelta agonist treatment increases skeletal muscle lipid metabolism without altering mitochondrial energy coupling: an in vivo magnetic resonance spectroscopy study. AB - Peroxisome proliferator-activated receptor-delta (PPARdelta) activation results in upregulation of genes associated with skeletal muscle fatty acid oxidation and mitochondrial uncoupling. However, direct, noninvasive assessment of lipid metabolism and mitochondrial energy coupling in skeletal muscle following PPARdelta stimulation has not been examined. Therefore, in this study we examined the response of a selective PPARdelta agonist (GW610742X at 5 or 100 mg.kg( 1).day(-1) for 8 days) on skeletal-muscle lipid metabolism and mitochondrial coupling efficiency in rats by using in vivo magnetic resonance spectroscopy (MRS). There was a decrease in the intramyocellular lipid-to-total creatine ratio as assessed by in vivo (1)H-MRS in soleus and tibialis anterior muscles by day 7 (reduced by 49 and 46%, respectively; P < 0.01) at the high dose. Following the (1)H-MRS experiment (day 8), [1-(13)C]glucose was administered to conscious rats to assess metabolism in the soleus muscle. The relative fat-vs.-carbohydrate oxidation rate increased in a dose-dependent manner (increased by 52 and 93% in the 5 and 100 mg.kg(-1).day(-1) groups, respectively; P < 0.05). In separate experiments where mitochondrial coupling was assessed in vivo (day 7), (31)P-MRS was used to measure hindlimb ATP synthesis and (13)C-MRS was used to measure the hindlimb tricarboxylic acid cycle flux (V(tca)). There was no alteration, at either dose, in mitochondrial coupling efficiency measured as the ratio of unidirectional ATP synthesis flux to V(tca). Soleus muscle GLUT4 expression was decreased by twofold, whereas pyruvate dehydrogenase kinase 4, carnitine palmitoyl transferase 1a, and uncoupling protein 2 and 3 expression was increased by two- to threefold at the high dose (P < 0.05). In summary, these are the first noninvasive measurements illustrating a selective PPARdelta-mediated decrease in muscle lipid content that was consistent with a shift in metabolic substrate utilization from carbohydrate to lipid. However, the mitochondrial-energy coupling efficiency was not altered in the presence of increased uncoupling protein expression. PMID- 17726148 TI - Obesity-associated mouse adipose stem cell secretion of monocyte chemotactic protein-1. AB - Studies showed that monocyte chemotactic protein-1 (MCP-1) concentrations are increased in obesity. In our current study, we demonstrate that plasma MCP-1 level in leptin-deficient ob/ob mice is significantly higher than in lean mice. Furthermore, we determined that basal adipose tissue MCP-1 mRNA levels are significantly higher in ob/ob mice compared with lean mice. To determine the mechanisms underlying obesity-associated increases in plasma and adipose tissue MCP-1 levels, we determined adipose tissue cell type sources of MCP-1 production. Our data show that adipose tissue stem cells (CD34(+)), macrophages (F4/80(+)), and stromal vascular fraction (SVF) cells express significantly higher levels of MCP-1 compared with adipocytes under both basal and lipopolysaccharide (LPS) stimulated conditions. Furthermore, basal and LPS-induced MCP-1 secretion levels were the same for both adipose F4/80(+) and CD34(+) cells, whereas adipose CD34(+) cells have twofold higher cell numbers (30% of total SVF cells) compared with F4/80(+) macrophages (15%). Our data also show that CD34(+) cells from visceral adipose tissue depots secrete significantly higher levels of MCP-1 ex vivo when compared with CD34(+) cells from subcutaneous adipose tissue depots. Taken together, our data suggest that adipose CD34(+) stem cells may play an important role in obesity-associated increases in plasma MCP-1 levels. PMID- 17726147 TI - Norepinephrine and rosiglitazone synergistically induce Elovl3 expression in brown adipocytes. AB - The Elovl3 gene, which putatively encodes for a protein involved in the elongation of saturated and monounsaturated fatty acids in the C20-C24 range, is expressed in murine liver, skin, and brown adipose tissue (BAT). In BAT, Elovl3 is dramatically upregulated during tissue activation in response to cold exposure, and functional data imply that ELOVL3 is a critical enzyme for lipid accumulation in brown adipocytes during the early phase of tissue recruitment. The activation of BAT is controlled by sympathetic nerve activity and norepinephrine release. By using primary cultures of brown adipocytes, we show here that the induced Elovl3 gene expression is synergistically regulated by norepinephrine and the peroxisome proliferator-activated receptor (PPAR) gamma ligand rosiglitazone. In addition, the potency of rosiglitazone to induce Elovl3 expression was several orders of magnitude higher than for the PPARalpha and PPARdelta ligands WY-14643 and L-165041, respectively. The maximal increase in mRNA level by norepinephrine and rosiglitazone is achieved by induced transcription as well as increased mRNA stability, and the whole process requires novel protein synthesis. We conclude that norepinehrine and PPARgamma, despite having different roles in brown adipocyte activation and differentiation, cooperate in expanding the intracellular lipid pool by synergistically stimulating Elovl3 expression. PMID- 17726149 TI - Vessel wall stiffness in type 1 diabetes and the central hemodynamic effects of acute hypoglycemia. AB - OBJECTIVE: To examine the effects of intravenous insulin and acute hypoglycemia on arterial wall stiffness and central hemodynamic responses in adults with and without type 1 diabetes. RESEARCH DESIGN AND METHODS: In 30 young male volunteers [10 nondiabetic (Group 1); 10 with type 1 diabetes, <5 yr duration (Group 2); 10 with type 1 diabetes, >15 yr duration (Group 3)], intravenous insulin was administered to provoke an acute autonomic reaction (R) to hypoglycemia. Heart rate, peripheral blood pressure, and pulse wave analysis (radial artery) were monitored. Augmentation index (AIx), a measure of arterial wall stiffness and wave reflection, and central arterial pressure were recorded. RESULTS: At baseline, no significant differences were observed between Groups 1 and 2 in either AIx or in central arterial pressure, but in Group 3, both measures were significantly higher. All three groups exhibited similar responses to intravenous infusion of insulin and to hypoglycemia: AIx fell progressively from baseline to R, peripheral systolic blood pressure increased, and central systolic pressure decreased. CONCLUSION: Compared with age- and sex-matched nondiabetic controls, people who had type 1 diabetes for a long duration had increased stiffness of vessel walls. The opposing responses in peripheral and central systolic pressures during hypoglycemia may be related to the reduction in AIx, which causes diminished amplification of the systolic pressure wave. Changes in AIx are probably mediated by a direct action of insulin on arterial endothelium, or changes in heart rate. These functional changes may contribute to the increased cardiovascular morbidity that is associated with type 1 diabetes of long duration. PMID- 17726151 TI - A SELDI-TOF MS study of the genetic and post-translational molecular heterogeneity of eosinophil cationic protein. AB - Eosinophil cationic protein (ECP), a secretory protein of the eosinophil granulocyte, is a basic and highly heterogeneous protein. This heterogeneity is dependent on polymorphisms in the ECP gene and post-translational modifications, and it affects the functional properties of the protein in terms of cytotoxicity. The aim of this study was to further investigate the molecular heterogeneity, hence, an affinity capture assay based on an antigen-antibody interaction with the surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF MS) technique was developed. Of three monoclonal antibodies tested, that is, EG2, 614, and 652, the 614 mab was chosen for the experiments. ECP heterogeneity of single individuals was studied in extracts of purified blood eosinophils, and the presence of approximately 5 major molecular species was demonstrated in each subject. ECP from subjects with different ECP 434(G>C) genotypes (arg97thr) showed mass differences corresponding to the amino acid shift from arginine to threonine. ECP purified from pooled leukocytes of large numbers of healthy blood donors demonstrated an extensive mass heterogeneity with approximately 10 major molecular species. By the use of a variety of glucosidases it was shown that this heterogeneity was mainly due to N-linked oligosaccharides on which sialic acid, galactose, and acetylglucosamine was positioned. We conclude that the SELDI-TOF MS technique using specific monoclonal antibodies is a convenient and versatile tool; by means of this technique, we could detect both genetic and post-translational causes of the molecular heterogeneity of the eosinophil cationic protein. PMID- 17726152 TI - Interactions of TANGO and leukocyte integrin CD11c/CD18 regulate the migration of human monocytes. AB - The TANGO gene was originally identified as a new member of the MIA gene family. It codes for a protein of yet unknown function. TANGO revealed a very broad expression pattern in contrast to the highly restricted expression pattern determined for the other family members. The only cells lacking TANGO expression are cells of the hematopoietic system. One of the major differences between mature hematopoietic cells and other tissue cells is the lack of adhesion until these cells leave the bloodstream. In this study, we observed that TANGO expression was induced after adhesion of human monocytic cells to substrate. To understand the mechanism of TANGO function during monocyte adhesion we isolated interacting proteins and found an interaction between TANGO and the leukocyte specific integrin CD11c. In functional assays, we observed reduced attachment of human monocytic cells to fibrinogen, ICAM-1 and to human microvascular endothelial cells (HMECs) after stimulation with recombinant TANGO protein. Additionally, the migrating capacity of premonocytic cells through fibrinogen or HMECs was increased after stimulation of these cells with recombinant TANGO. Therefore, we suggest that TANGO reduced the attachment to fibrinogen or other cell adhesion molecules. As TANGO does not compete for CD11c ligand binding directly, we hypothesize TANGO function by modulation of integrin activity. Taken together, the results from this study present TANGO as a novel ligand for CD11c, regulating migratory processes of hematopoietic cells. PMID- 17726153 TI - Adoptive transfer of murine syngeneic graft-vs.-host disease by CD4+ T cells. AB - Syngeneic graft-vs.-host disease (SGVHD) develops in rodents following the treatment of lethally irradiated, bone marrow (BM) reconstituted animals with a short course of the immunosuppressive agent cyclosporine A (CsA). Using an in vivo depletion approach, we recently demonstrated that CD4(+), but not CD8(+), T cells participated in inducing SGVHD. Studies were therefore undertaken to adoptively transfer SGVHD into lethally irradiated, syngeneic BM reconstituted secondary recipients. Whole T cell populations as well as purified CD4(+)T cells isolated from SGVHD, but not normal or transplant control, animals mediated the transfer of SGVHD into secondary recipients. These cells have an apparent specificity for enteric bacterial antigens. The pathologic process that developed was identical to that observed in the animals with de novo SGVHD after syngeneic BMT and CsA therapy. It was shown that a radiation-sensitive mechanism prevented the transfer of SGVHD into normal, nonirradiated secondary recipients. The ability to reproducibly transfer SGVHD into secondary recipients will enhance our ability to study regulatory mechanisms that are altered during CsA therapy and permit the development of murine CsA-induced SGVHD. PMID- 17726154 TI - Modulation of CD1d-restricted NKT cell responses by CD4. AB - CD4+ and CD4- NKT cell populations have been shown to be functionally distinct, but the role of CD4 molecules in NKT cell activation is not clear. Here, we have used human CD1d-restricted NKT cell clones to investigate the contribution of CD4 to NKT cell functional responses. Coligation of CD4 with the TCR/CD3 complex resulted in enhanced cytokine secretion and increased calcium flux by CD4+ NKT cell clones, indicating that CD4 is functionally active in these cells. CD4 blockade specifically inhibited cytokine secretion and proliferation of CD4+ NKT cell clones in response to CD1d+ APCs but did not affect cytotoxicity, suggesting that CD4 preferentially modulates some NKT cell functional responses and not others. Anti-CD4 mAb treatment inhibited NKT cell responses to both MHC class II(+) and MHC class II(-) APCs, indicating that its effect was not due to blocking CD4 binding to MHC class II molecules on APCs. The inhibitory effect of the anti-CD4 mAb also did not require recognition of CD1d by the NKT cell, since calcium flux was reduced in response to anti-CD3 mAb stimulation. Western blot analysis revealed that anti-CD4 treatment resulted in increased phosphorylation of an inhibitory site of p56(lck) (tyrosine 505). Thus, CD4 blockade interferes with the course of CD3-mediated signaling events in NKT cells. These results indicate that CD4 can contribute to NKT cell activation independently of the presence of a CD4-ligand on APCs and suggest that it preferentially modulates cytokine and proliferative responses. PMID- 17726155 TI - Parawixin1: a spider toxin opening new avenues for glutamate transporter pharmacology. AB - Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. After release from glutamatergic nerve terminals, glial and neuronal glutamate transporters remove glutamate from the synaptic cleft to terminate synaptic transmission and to prevent neuronal damage by excessive glutamate receptor activation. In this issue of Molecular Pharmacology, Fontana et al. (p. 1228) report on the action of a venom compound, Parawixin1, on excitatory amino acid transporters (EAATs). They demonstrate that this agent selectively affects a glial glutamate transporter, EAAT2, by specifically increasing one particular step of the glutamate uptake cycle. Disturbed glutamate homeostasis seems to be a pathogenetic factor in several neurodegenerative disorders. Because EAAT2 is a key player in determining the extracellular glutamate concentration in the mammalian brain, drugs targeting this protein could prevent glutamate excitotoxicity without blocking glutamatergic transmission. Its specificity and selectivity makes Parawixin1 a perfect starting point to design small molecules for the treatment of pathological conditions caused by alterations of glutamate homeostasis. PMID- 17726156 TI - Mitochondrial complex I inhibitor rotenone-elicited dopamine redistribution from vesicles to cytosol in human dopaminergic SH-SY5Y cells. AB - Parkinson's disease is a chronic neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra. Rotenone, a pesticide, produces selective degeneration of dopaminergic neurons and motor dysfunction in rats. To determine the mechanisms underlying rotenone-induced neuronal death, we investigated whether intracellular dopamine plays a role in rotenone (0.1-0.4 microM)-induced apoptosis, using an in vitro model of human dopaminergic SH-SY5Y cells. The 40% decrease of dopamine content by inhibition of dopamine synthesis suppressed rotenone-induced apoptosis. On the other hand, the 30% increase of dopamine content by inhibition of dopamine metabolism enhanced rotenone-induced apoptosis. Depletion of intracellular dopamine using reserpine (0.1-10 microM) also prevented rotenone-induced apoptosis, and this effect was counteracted by dopamine (10-100 microM) replenishment. Inhibition of dopamine reverse transport increased cytosolic dopamine and enhanced rotenone-induced apoptosis. We examined the intracellular localization of dopamine in rotenone-treated cells immunocytochemically and quantitatively. Rotenone induced dopamine redistribution from vesicles to the cytosol. In this process, rotenone stimulated reactive oxygen species and protein carbonylation and decreased an antioxidant, glutathione. Addition of an antioxidant, N-acetylcysteine (3 mM), prevented dopamine being expelled from vesicles and inhibited rotenone-induced apoptosis. Our findings demonstrate that rotenone-generated reactive oxygen species are involved in dopamine redistribution to the cytosol, which in turn may play a role in rotenone-induced apoptosis of dopaminergic cells. PMID- 17726157 TI - Inhibition of renal dipeptidyl peptidase IV enhances peptide YY1-36-induced potentiation of angiotensin II-mediated renal vasoconstriction in spontaneously hypertensive rats. AB - Dipeptidyl peptidase IV inhibitors are a new class of antidiabetic drugs. It is urgent, therefore, to fully understand the pharmacology of these inhibitors. Although dipeptidyl peptidase IV metabolizes at least 24 endogenous substrates, the pharmacological consequences of inhibiting the metabolism of most of these substrates is unknown. Our previous results show that Y(1) receptors, but not Y(2) receptors, enhance renovascular responses to angiotensin II in kidneys from genetically susceptible animals (spontaneously hypertensive rats). Dipeptidyl peptidase IV converts peptide YY(1-36) (circulating hormone) to peptide YY(3-36), and peptide YY(1-36) is a Y(1)-receptor agonist, whereas peptide YY(3-36) is a selective Y(2)-receptor agonist. Therefore, it is conceivable that inhibition of dipeptidyl peptidase IV in genetically susceptible kidneys may increase the ability of peptide YY(1-36) to potentiate angiotensin II-induced renal vasoconstriction. Here we demonstrate that in kidneys from spontaneously hypertensive rats 1) peptide YY(1-36) potentiates renovascular responses to angiotensin II, whereas peptide YY(3-36) has little effect, 2) 3-N-[(2S,3S)-2 amino-3-methylpentanoyl]-1,3-thiazolidine (P32/98) (dipeptidyl peptidase IV inhibitor) augments the ability of peptide YY(1-36) to enhance renovascular responses to angiotensin II, 3) dipeptidyl peptidase IV is expressed in preglomerular microvessels and glomeruli, 4) kidneys metabolize arterial PYY(1 36) to PYY(3-36) via a mechanism blocked by P32/98, and 5) preglomerular microvessels and glomeruli convert peptide YY(1-36) to peptide YY(3-36), and this conversion is inhibited by P32/98. We conclude that dipeptidyl peptidase IV is expressed in the renal microcirculation and inhibition of this ecto-enzyme causes arterial PYY(1-36) to more effectively enhance angiotensin II-induced renal vasoconstriction in genetically susceptible kidneys. PMID- 17726158 TI - Modulation of airway responses to influenza A/PR/8/34 by Delta9 tetrahydrocannabinol in C57BL/6 mice. AB - Delta(9)-tetrahydrocannabinol (Delta(9)-THC) has been widely established as a modulator of host immune responses. Accordingly, the objective of the present study was to examine the effects of Delta(9)-THC on the immune response within the lungs and associated changes in the morphology of the bronchiolar epithelium after one challenge with a nonlethal dose of the influenza virus A/PR/8 (PR8). C57BL/6 mice were treated by oral gavage with Delta(9)-THC and/or vehicle (corn oil) for 5 consecutive days. On day 3, mice were instilled intranasally with 50 plaque-forming units of PR8 and/or vehicle (saline) 4 h before Delta(9)-THC exposure. Mice were subsequently killed 7 and 10 days postinfection (dpi). Viral hemagglutinin 1 (H1) mRNA levels in the lungs were increased in a dose-dependent manner with Delta(9)-THC treatment. Enumeration of inflammatory cell types in bronchoalveolar lavage fluid showed an attenuation of macrophages and CD4(+) and CD8(+) T cells in Delta(9)-THC-treated mice compared with controls. Likewise, the magnitude of inflammation and virus-induced mucous cell metaplasia, as assessed by histopathology, was reduced in Delta(9)-THC-treated mice by 10 dpi. Collectively, these results suggest that Delta(9)-THC treatment increased viral load, as assessed by H1 mRNA levels, through a decrease in recruitment of macrophages and lymphocytes, particularly CD4(+) and CD8(+) T cells, to the lung. PMID- 17726159 TI - The immunomodulator FTY720 has a direct cytoprotective effect in oligodendrocyte progenitors. AB - The immunomodulator 2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol (FTY720) has promising therapeutic effects in multiple sclerosis (MS), a degenerative disease in which demyelination of the central nervous system is accompanied by death of oligodendrocytes (OLGs), the myelin-producing cells. In vivo phosphorylation of FTY720 generates an agonist for G protein-coupled receptors for sphingosine-1-phosphate, a lipid mediator that plays a crucial role in the stimulation of OLG survival by neurotrophin-3 (NT-3). The mechanisms underlying the action of FTY720 in MS are not clearly understood, although the effects of this drug in autoimmune diseases are thought to stem from its ability to reduce lymphocyte infiltration and inflammation. Interestingly, we now found that FTY720 also has a direct effect on OLG progenitors. Treatment of these cells with FTY720 causes activation of extracellular signal-regulated kinase 1/2 and Akt, accompanied by protection from apoptosis. However, FTY720 also arrested OLG differentiation. Importantly, this effect was counteracted by NT-3, which not only enhanced the survival of OLG progenitors induced by FTY720 but also stimulated their maturation. Altogether, these observations suggest that in addition to its immunosuppressive functions, FTY720 could also have a beneficial effect in MS by direct action on OLG progenitors. However, the finding that FTY720 blocks the differentiation of these cells raises the question of whether MS therapies with FTY720 should include the use of differentiation-enhancing factors such as NT-3. This approach would ensure both protection of existing OLG progenitor pools against immune-mediated insults as well as stimulation of remyelination by enhancing the maturation of these cells. PMID- 17726160 TI - New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients. AB - We have generated a large, unique database that includes morphologic, clinical, cytogenetic, and follow-up data from 2124 patients with myelodysplastic syndromes (MDSs) at 4 institutions in Austria and 4 in Germany. Cytogenetic analyses were successfully performed in 2072 (97.6%) patients, revealing clonal abnormalities in 1084 (52.3%) patients. Numeric and structural chromosomal abnormalities were documented for each patient and subdivided further according to the number of additional abnormalities. Thus, 684 different cytogenetic categories were identified. The impact of the karyotype on the natural course of the disease was studied in 1286 patients treated with supportive care only. Median survival was 53.4 months for patients with normal karyotypes (n = 612) and 8.7 months for those with complex anomalies (n = 166). A total of 13 rare abnormalities were identified with good (+1/+1q, t(1q), t(7q), del(9q), del(12p), chromosome 15 anomalies, t(17q), monosomy 21, trisomy 21, and -X), intermediate (del(11q), chromosome 19 anomalies), or poor (t(5q)) prognostic impact, respectively. The prognostic relevance of additional abnormalities varied considerably depending on the chromosomes affected. For all World Health Organization (WHO) and French American-British (FAB) classification system subtypes, the karyotype provided additional prognostic information. Our analyses offer new insights into the prognostic significance of rare chromosomal abnormalities and specific karyotypic combinations in MDS. PMID- 17726161 TI - Excessive exposure to anionic surfaces maintains autoantibody response to beta(2) glycoprotein I in patients with antiphospholipid syndrome. AB - Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder associated with autoantibodies to phospholipid (PL)-binding proteins, such as beta(2)-glycoprotein I (beta(2)GPI). We have recently reported that binding of beta(2)GPI to anionic PL facilitates processing and presentation of the cryptic beta(2)GPI epitope that activates pathogenic autoreactive T cells. To clarify mechanisms that induce sustained presentation of the dominant antigenic beta(2)GPI determinant in patients with APS, T-cell proliferation induced by beta(2)GPI-treated phosphatidylserine liposome (beta(2)GPI/PS) was evaluated in bulk peripheral blood mononuclear cell cultures. T cells from patients with APS responded to beta(2)GPI/PS in the presence of immunoglobulin G (IgG) anti beta(2)GPI antibodies derived from APS plasma, and this response was completely inhibited either by the depletion of monocytes or by the addition of anti FcgammaRI antibody. These findings indicate that efficient presentation of the cryptic determinants can be achieved by monocytes undergoing FcgammaRI-mediated uptake of beta(2)GPI-bound anionic surfaces in the presence of IgG anti beta(2)GPI antibodies. Finally, beta(2)GPI-bound oxidized LDL or activated platelets also induced the specific T-cell response. Continuous exposure to these anionic surfaces may play a critical role in maintaining the pathogenic anti beta(2)GPI antibody response in patients with APS. PMID- 17726162 TI - Tissue factor activation: is disulfide bond switching a regulatory mechanism? AB - A majority of tissue factor (TF) on cell surfaces exists in a cryptic form (ie, coagulation function inactive) but retains its functionality in cell signaling. Recent studies have suggested that cryptic TF contains unpaired cysteine thiols and that activation involves the formation of the disulfide bond Cys186-Cys 209 and that protein disulfide isomerase (PDI) regulates TF coagulant and signaling activities by targeting this disulfide bond. This study was carried out to investigate the validity of this novel concept. Although treatment of MDA 231 tumor cells, fibroblasts, and stimulated endothelial cells with the oxidizing agent HgCl(2) markedly increased the cell-surface TF coagulant activity, the increase is associated with increased anionic phospholipids at the cell surface. Annexin V, which binds to anionic phospholipids, attenuated the increased TF coagulant activity. It is noteworthy that treatment of cells with reducing agents also increased the cell surface TF activity. No evidence was found for either detectable expression of PDI at the cell surface or association of TF with PDI. Furthermore, reduction of PDI with the gene silencing had no effect on either TF coagulant or cell signaling functions. Overall, the present data undermine the recently proposed hypothesis that PDI-mediated disulfide exchange plays a role in regulating TF procoagulant and cell signaling functions. PMID- 17726163 TI - Zebrafish as a model for defining the functional impact of mammalian ferroportin mutations. AB - The term hemochromatosis represents a group of inherited disorders leading to iron overload. Mutations in HFE, HJV, and TfR2 cause autosomal-recessive forms of hemochromatosis. Mutations in ferroportin, however, result in dominantly inherited iron overload. Some mutations (H32R and N174I) in ferroportin lead to macrophage iron loading, while others (NI44H) lead to hepatocyte iron loading. Expression of H32R or N174I ferroportin cDNA in zebrafish leads to severe iron limited erythropoiesis. Expression of wild-type ferroportin or hepcidin-resistant ferroportin (N144H) does not affect erythropoiesis. Zebrafish provides a facile way of identifying which ferroportin mutants may lead to macrophage iron loading. PMID- 17726164 TI - The importance of HLA-DPB1 in unrelated donor hematopoietic cell transplantation. AB - Hematopoietic cell transplantation (HCT) from an HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 allele-matched unrelated donor is a well-recognized life-saving treatment modality for patients with hematologic disorders. The morbidity and mortality from clinically significant acute graft-versus-host disease (aGVHD) remains a limitation. The extent to which transplantation outcome may be improved with donor matching for HLA-DP is not well defined. The risks of aGVHD, relapse, and mortality associated with HLA-DPB1 allele mismatching were determined in 5929 patients who received a myeloablative HCT from an HLA-A-, HLA-B-, HLA-C-, HLA DRB1-, and HLA-DQB1-matched or -mismatched donor. There was a statistically significantly higher risk of both grades 2 to 4 aGVHD (odds ratio [OR] = 1.33; P < .001) and grades 3 to 4 aGVHD (OR = 1.26; P < .001) after HCT from an HLA-DPB1 mismatched donor compared with a matched donor. The increased risk of aGVHD was accompanied by a statistically significantly decrease in disease relapse (hazard ratio [HR] = 0.82; P = .01). HLA-DPB1 functions as a classical transplantation antigen. The increased risk of GVHD associated with HLA-DPB1 mismatching is accompanied by a lower risk of relapse. Knowledge of the DPB1 matching status prior to transplantation will aid in more precise risk stratification for the individual patient. PMID- 17726165 TI - A microRNA-regulated lentiviral vector mediates stable correction of hemophilia B mice. AB - A longstanding goal for the treatment of hemophilia B is the development of a gene transfer strategy that can maintain sustained production of clotting factor IX (F.IX) in the absence of an immune response. To this end, we have sought to use lentiviral vectors (LVs) as a means for systemic gene transfer. Unfortunately, initial evaluation of LVs expressing F.IX from hepatocyte-specific promoters failed to achieve sustained F.IX expression in hemophilia B mice due to the induction of an anti-F.IX cellular immune response. Further analysis suggested that this may be a result of off-target transgene expression in hematopoietic-lineage cells of the spleen. In order to overcome this problem, we modified our vector to contain a target sequence for the hematopoietic-specific microRNA, miR-142-3p. This eliminated off-target expression in hematopoietic cells, and enabled sustained gene transfer in hemophilia B mice for more than 280 days after injection. Treated mice had more than 10% normal F.IX activity, no detectable anti-F.IX antibodies, and were unresponsive to F.IX immunization. Importantly, the mice survived tail-clip challenge, thus demonstrating phenotypic correction of their bleeding diathesis. This work, which is among the first applications to exploit the microRNA regulatory pathway, provides the basis for a promising new therapy for the treatment of hemophilia B. PMID- 17726166 TI - A model of segmental duplication formation in Drosophila melanogaster. AB - Segmental duplications (SDs) are low-copy repeats of DNA segments that have long been recognized to be involved in genome organization and evolution. But, to date, the mechanism of their formation remains obscure. We propose a model for SD formation that we name "duplication-dependent strand annealing" (DDSA). This model is a variant of the synthesis-dependent strand annealing (SDSA) model--a double-strand break (DSB) homologous repair model. DSB repair in Drosophila melanogaster genome usually occurs primarily through homologous repair, more preferentially through the SDSA model. The DDSA model predicts that after a DSB, the search for an ectopic homologous region--here a repeat--initiates the repair. As expected by the model, the analysis of SDs detected by a computational analysis of the D. melanogaster genome indicates a high enrichment in transposable elements at SD ends. It shows moreover a preferential location of SDs in heterochromatic regions. The model has the advantage of also predicting specific traces left during synthesis. The observed traces support the DDSA model as one model of formation of SDs in D. melanogaster genome. The analysis of these DDSA signatures suggests moreover a sequestration of the dissociated strand in the repair complex. PMID- 17726167 TI - Moulds and asthma: time for indoor climate change? PMID- 17726168 TI - Maternal diet vs lack of exposure to sunlight as the cause of the epidemic of asthma, allergies and other autoimmune diseases. PMID- 17726169 TI - Air pollution, human health, climate change and you. PMID- 17726171 TI - Reduction of persistent air leak with endoscopic valve implants. AB - The standard management of air leaks due to persistent bronchopleural fistula involves chest drainage and occasionally pleurodesis, with intractable cases requiring surgical decortication or surgical repair. However, some of these patients may be at high risk for surgery, particularly if they have already had thoracic surgery or have other medical problems; for this group there is a need for less invasive methods of stopping or reducing air leaks. Emphasys endobronchial valves (EBV) are occlusive devices designed primarily for endoscopic lung volume reduction in emphysema. Because the device is a one-way inspiratory airway blocker, it is possible that it could be used in controlling persistent air leaks while maintaining the drainage of secretions. Two cases are reported of persistent air leaks that were managed by endoscopic occlusion with EBV. In one case complete stoppage of the air leak was achieved with immediate clinical benefits. The second patient died 5 days after treatment from additional complications apparently not related to the procedure. Endobronchial blockage may be a useful salvage procedure for patients with persistent air leak for whom there is no other treatment available. PMID- 17726172 TI - Critical care as part of respiratory training in the UK. PMID- 17726170 TI - Challenges in pulmonary fibrosis. 3: Cystic lung disease. AB - Cystic lung disease is a frequently encountered problem caused by a diverse group of diseases. Distinguishing true cystic lung disease from other entities, such as cavitary lung disease and emphysema, is important given the differing prognostic implications. In this paper the features of the cystic lung diseases are reviewed and contrasted with their mimics, and the clinical and radiographic features of both diffuse (pulmonary Langerhans' cell histiocytosis and lymphangioleiomyomatosis) and focal or multifocal cystic lung disease are discussed. PMID- 17726173 TI - Effect of azithromycin on primary bronchial epithelial cells derived from stable lung allografts. PMID- 17726174 TI - NICE guidance for screening for malnutrition: implications for lung cancer services. PMID- 17726175 TI - Breathing techniques in the management of asthma. PMID- 17726176 TI - Massive pulmonary arteriovenous malformation presenting with tamponading haemothorax. PMID- 17726177 TI - The functions of plant TIR domains. AB - The Toll-interleukin-1 receptor (TIR) domain is found in innate immune molecules of insects, animals, and plants. There is a marked conservation of the signaling pathways used by TIR domain-containing immune receptors in animals. In plants, pathways involving TIR domain-containing proteins are not as well understood, but data are beginning to suggest important differences between the functions of plant and animal proteins. Plant Resistance proteins use their TIR domains for pathogen detection, and they may also function in the nucleus to direct the expression of genes involved in defense responses. This shows that plants have used their TIR domains to perform a multitude of duties and have expanded the functions of the TIR domain beyond those seen in animals. PMID- 17726178 TI - Structure and function of the PB1 domain, a protein interaction module conserved in animals, fungi, amoebas, and plants. AB - Proteins containing the PB1 domain, a protein interaction module conserved in animals, fungi, amoebas, and plants, participate in diverse biological processes. The PB1 domains adopt a ubiquitin-like beta-grasp fold, containing two alpha helices and a mixed five-stranded beta sheet, and are classified into groups harboring an acidic OPCA motif (type I), the invariant lysine residue on the first beta strand (type II), or both (type I/II). The OPCA motif of a type I PB1 domain forms salt bridges with basic residues, especially the conserved lysine, of a type II PB1 domain, thereby mediating a specific PB1-PB1 heterodimerization, whereas additional contacts contribute to high affinity and specificity of the modular interaction. The canonical PB1 dimerization is required for the formation of complexes between p40(phox) and p67(phox) (for activation of the NADPH oxidase crucial for mammalian host defense), between the scaffold Bem1 and the guanine nucleotide exchange factor Cdc24 (for polarity establishment in yeasts), and between the polarity protein Par6 and atypical protein kinase C (for cell polarization in animal cells), as well as for the interaction between the mitogen activated protein kinase kinase kinases MEKK2 or MEKK3 and the downstream target mitogen-activated protein kinase kinase MEK5 (for early cardiovascular development in mammals). PB1 domains can also mediate interactions with other protein domains. For example, an intramolecular interaction between the PB1 and PX domains of p40(phox) regulates phagosomal targeting of the microbicidal NADPH oxidase; the PB1 domain of MEK5 is likely responsible for binding to the downstream kinase ERK5, which lacks a PB1 domain; and the scaffold protein Nbr1 associates through a PB1-containing region with titin, a sarcomere protein without a PB1 domain. This Review describes various aspects of PB1 domains at the molecular and cellular levels. PMID- 17726179 TI - Clinical depression versus distress among patients with type 2 diabetes: not just a question of semantics. PMID- 17726181 TI - Effect of chromium supplementation on glucose metabolism and lipids: a systematic review of randomized controlled trials. PMID- 17726183 TI - Metabolic syndrome is associated with adherence to an unhealthy diet. PMID- 17726184 TI - Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. PMID- 17726186 TI - Accuracy and predictive value of classification schemes for ketosis-prone diabetes. PMID- 17726188 TI - Accuracy of administrative coding for type 2 diabetes in children, adolescents, and young adults. PMID- 17726190 TI - Consensus statement on the worldwide standardization of the hemoglobin A1C measurement: the American Diabetes Association, European Association for the Study of Diabetes, International Federation of Clinical Chemistry and Laboratory Medicine, and the International Diabetes Federation. PMID- 17726191 TI - The Avandia debate. PMID- 17726192 TI - Sliding-scale insulin: more evidence needed before final exit? PMID- 17726193 TI - Point: HOMA--satisfactory for the time being: HOMA: the best bet for the simple determination of insulin sensitivity, until something better comes along. PMID- 17726194 TI - Counterpoint: appreciating homeostasis model assessment: more useful earlier rather than later. PMID- 17726195 TI - Fenofibrate reduces intestinal cholesterol absorption via PPARalpha-dependent modulation of NPC1L1 expression in mouse. AB - Fibrates, including fenofibrate, exert their biological effects by binding peroxisome proliferator-activated receptor alpha (PPARalpha), a member of the nuclear receptor superfamily of ligand-activated transcription factors. Treatment with PPARalpha agonists enhances fatty acid oxidation, decreases plasma triglycerides, and may promote reverse cholesterol transport. In addition, fibrate administration can reduce intestinal cholesterol absorption in patients, although the molecular mechanism for this effect is unknown. Because Niemann-Pick C1-Like 1 (NPC1L1) is already known to be a critical protein for cholesterol absorption, we hypothesized that fenofibrate might modulate NPC1L1 expression to alter intestinal cholesterol transport. Here, we find that fenofibrate-treated wild-type mice have decreased fractional cholesterol absorption (35-47% decrease) and increased fecal neutral sterol excretion (51-83% increase), which correspond to decreased expression of NPC1L1 mRNA and protein (38-66% decrease) in the proximal small intestine. These effects of fenofibrate are dependent on PPARalpha, as Ppar alpha-knockout mice fail to respond like wild-type littermates. Fenofibrate affects the ezetimibe-sensitive pathway and retains the ability to decrease cholesterol absorption and NPC1L1 mRNA expression in chow-fed liver X receptor alpha/beta-double-knockout mice and high-cholesterol- or cholic acid-fed wild-type mice. These data demonstrate that fenofibrate specifically acts via PPARalpha to decrease cholesterol absorption at the level of intestinal NPC1L1 expression. PMID- 17726196 TI - Identification of squalamine in the plasma membrane of white blood cells in the sea lamprey, Petromyzon marinus. AB - It is well established that innate mechanisms play an important role in the immunity of fish. Antimicrobial peptides have been isolated and characterized from several species of teleosts. Here, we report the isolation of an antimicrobial compound from the blood of bacterially challenged sea lamprey, Petromyzon marinus. An acetic acid extract from the blood cells of challenged fish was subjected to solid-phase extraction, cation-exchange chromatography, gel filtration chromatography, and reverse-phase high-performance liquid chromatography, with the purified fractions assayed for antimicrobial activity. Surprisingly, antimicrobial activity in these fractions originated from squalamine, an aminosterol previously identified in the dogfish shark, Squalus acanthias. Further chromatographic and mass spectrometric analyses confirmed the identity of squalamine, an antimicrobial and antiangiogenic agent, in the active fraction from the sea lamprey blood cells. Immunocytochemical analysis localized squalamine to the plasma membrane of white blood cells. Therefore, we postulate that squalamine has an important role in the innate immunity that defends the lamprey against microbial invasion. The full biochemical and immunological roles of squalamine in the white blood cell membrane remain to be investigated. PMID- 17726197 TI - Cheap solutions for big problems? PMID- 17726198 TI - The effect of physical activity on the knee joint: is it good or bad? PMID- 17726209 TI - Stomal varices: a rare cause of stomal hemorrhage. A report of three cases. AB - Stomal varices secondary to portal hypertension are a rare but potentially fatal cause of hemorrhage. Management, determined by the site of the bleeding, centers on preventing additional bleeds and may include providing local pressure, applying silver nitrate, injection sclerotherapy, suture ligation of the bleeding point, and/or the placement of transjugular intrahepatic portosystemic shunts and refashioning the stoma. Two patients (60- and 69-year-old women) had panproctocolectomy for inflammatory bowel disease and presented at the authors' hospital with bleeding from the ileostomy 1 and 19 years, respectively, following the creation of their stomas. A third patient (a 72-year-old man) bled from an end colostomy following an abdominoperineal resection for Duke's C rectal adenocarcinoma performed 3 years previous. All three patients had recurrent admissions for stomal bleeding and stomal varices secondary to portal hypertension and were initially treated with local measures (pressure, silver nitrate, and suture ligation). Two had undergone revision of their stomas prior to current treatment. One patient responded to local treatment but later died due to liver failure, one stopped bleeding after transjugular portosystemic shunt placement, and one died from metastatic cancer. Clinicians should maintain a high index of suspicion of stomal varices in patients with underlying liver disease who present with recurrent stomal bleeds and provide appropriate treatment to stop active bleeding and reduce portal venous pressure. PMID- 17726210 TI - Misconceptions about protein requirements for wound healing: results of a prospective study. AB - The successful treatment of protein malnutrition is critical for patient healing but traditional estimates of the amount of calories and protein needed for wound patients have been empiric. In particular, only the presence of a wound, not its severity or extent, is currently included as a stratifying "stress factor." To 1) ascertain reasons for feeding failure, 2) evaluate a hypothesis that patients with wounds require more protein than is generally recommended in the literature, and 3) affirm that wound burden effects protein requirements, a 1-year, descriptive, prospective study was conducted involving 150 tube-fed patients with (n = 93) and without (n = 57) wounds admitted to a long-term, acute care facility. On admission, 11% of wound and 21% of non-wound patients had normal pre albumin levels. Using an aggressive protein provision regimen, pre-albumin levels improved in 42% of wound patients (mean 36.9 days) and in 46% of non-wound patients (mean 29.7 days). The most common cause of feeding failure was inadequate provision or assimilation of protein. Signs and symptoms of overfeeding were not observed. The average maximum amount of protein provided to patients whose pre-albumin improved was significantly higher in the wound (1.85 g/Kg/day) than in the non-wound (1.47 g/Kg/day) group (P = .0002). Among wound patients whose pre-albumin improved, a trend between higher wound burden (defined by total Pressure Ulcer Scale for Healing score) and maximum amounts of protein provided was seen. In addition to the need for more research in this area, study findings suggest that commonly estimated protein requirements for wound patients are too low and that better tools and procedures for protein assessment and maintenance need to be implemented. PMID- 17726211 TI - Implementing a wound care resource nurse program. AB - Nurses are leaders in implementing innovations that can create positive outcomes in the prevention and management of pressure ulcers in patients admitted to acute care hospitals. Believing that nurses knowledgeable in best practices could impact prevalence, incidence, and care of pressure ulcers, an educational program was developed in a Canadian healthcare system to inform and empower nurses providing skin and wound care. The program afforded participants the opportunity to acquire the knowledge and skill to recognize patients at risk for developing pressure ulcers and to independently treat Stage I and Stage II pressure ulcers and skin breakdown related to moisture, friction, and shear. The program includes evidence-based practice recommendations and highlights the Best Practice Guidelines developed by the Registered Nurses Association of Ontario, a provincial body taking an active role in the development, implementation, and evaluation of published guidelines derived from global research literature synthesis. Pre- and post participation assessment of 65 nurse participants from three hospitals deemed the program successful in terms of knowledge and fulfillment of their educational expectations. Organizational support to implement the skin and wound care resource nurse role was encouraging and medical directives for Stage I and Stage II pressure ulcers by nurses were implemented. Evaluation and monitoring of program outcomes, including pressure ulcer incidence rates, continue. PMID- 17726213 TI - Amniotic membrane transplantation. PMID- 17726215 TI - Prophylactic subconjunctival cefuroxime during cataract surgery in patients with a penicillin allergy. AB - The incidence of cross-reaction after subconjunctival cefuroxime following cataract surgery in penicillin allergy patients is not common and therefore cefuroxime with its better spectrum of action and lower toxicity is probably a better choice than gentamycin. PMID- 17726214 TI - Sutureless levator plication by conjunctival route: a new technique. AB - The experiences of sutureless levator plication by conjunctival route surgery are described in 80 primary operations performed for all grades of congenital ptosis in the past 2 years. The surgical steps, postoperative care and postoperative complications are reviewed. PMID- 17726216 TI - Competitive analysis of intraoperative adjustable suture with conventional suture technique in strabismus surgery. AB - We compared the effectiveness of fixed conventional strabismus surgery (CSG) with a one-stage intraoperative adjustable suture technique in 88 patients undergoing strabismus surgery (ASG) either with fixed conventional (38) or intraoperative adjustable suture (50) technique. The mean correction of deviation with both near fixation and distant-fixation for the ASG and CSG were not different. One-stage intraoperative adjustable suture technique is safe and effective method for strabismus surgery for cooperative patients. PMID- 17726217 TI - Visual acuity and diabetic maculopathy. AB - We investigated the relationship between visual acuity (VA) and glycosylated hemoglobin, and the presentation and type of diabetic maculopathy retrospectively from 2000 to 2003. Data on 103 eyes of 75 patients were gathered. No statistically significant correlation was found between serum HbA1c with maculopathy type. VA is a poor predictor for the presence or absence of clinically significant diabetic maculopathy and type of maculopathy, emphasizing the importance of systematic screening for and early treatment of maculopathy before visual loss. PMID- 17726218 TI - Clinical evaluation of blue-light blocker foldable acrylic IOL (HMY). AB - Efficacy and safety of blue-light-filtering acrylic IOL (HMY) were assessed and proven from 3 months to 1 year of postoperative follow-up in a clinical study performed on 80 eyes of 45 patients. Postoperative corrected visual acuity of all the eyes was 6/12 or better and 78.8% of them achieved higher than 6/6. The rate of mean corneal endothelial cell density decrease stood at 5.0%. Mild complications were observed, but none were serious. PMID- 17726220 TI - Diagnostic ability of different tools for detection of glaucoma with confocal scanning laser tomography (Heidelberg Retina Tomograph II). AB - We evaluated the diagnostic ability of various diagnostic tools to detect glaucomatous damage in 101 normal eyes and 102 glaucomatous eyes. Mikelberg's linear discriminant function (LDF) obtained the best sensitivity followed by our own four formulas. With respect to specificity, Burk's LDF showed better results than Mikelberg's LDF and our formulae. Several Heidelberg retina tomograph analysis tools are useful to discriminate healthy from patients with glaucoma. Alternative tools based on normative databases derived from different autochthon populations add evidence needed to support their global use. PMID- 17726219 TI - Intravitreal triamcinolone for cystoid macular edema related to branch retinal vein occlusion. AB - We retrospectively evaluated the effectiveness of intravitreal triamcinolone in treating 19 eyes with macular edema related to branch retinal vein occlusion (BRVO). Eyes with nonischemic BRVO respond more favorably than those with ischemic BRVO. A single injection of intravitreal triamcinolone led to elevated intraocular pressure in 3 of 19 eyes (16%). Half of phakic eyes had progression of cataract. Retreatment may be necessary. PMID- 17726221 TI - Multivariate analysis of structural parameters of the optic nerve head assessed by means of confocal scanning laser (Heidelberg Retina Tomograph II). AB - We evaluated the optic nerve head parameters measured by confocal scanning laser that discriminated between normal and glaucomatous subjects in 97 normal eyes and 94 glaucomatous eyes. Several different linear regression formulas can discriminate the presence of glaucomatous. The use of linear regression functions of HRT parameters elaborated from autochthon population around the world will add the amounts of evidence needed to support the global use of these functions. PMID- 17726222 TI - Is transpupillary thermotherapy applicable to the treatment of age-related macular degeneration with pigment epithelial detachment? AB - The cause of pigment epithelial tears at the edge of a pigment epithelial detachment (PED) following transpupillary thermotherapy in eyes with associated age-related macular degeneration is unclear. We have treated 2 eyes which had a PED with TTT. Our findings suggest pigment epithelial tears are probably related to the shape of the PED and TTT should not applied to a balloon-shaped PED. PMID- 17726223 TI - Occult giant cell arteritis and steroid therapy: how urgent is urgent? AB - We report two cases of sudden loss of vision in the second eye, within few hours of loss of vision in the first, in association with occult giant cell arteritis. Both cases presented with bilateral disc edema. The importance of starting steroid therapy to prevent sight or life threatening complications, as soon as a diagnosis is suspected is emphasized. PMID- 17726224 TI - Spontaneous resolution of unilateral vitreomacular traction. AB - Vitreomacular traction (VMT) caused visual symptoms in two healthy young adults but spontaneously resolved within four weeks without any sequelae. Optical coherence tomography (OCT) and fundus photographs proved vital in documenting the rare complete resolution of VMT. It is prudent to monitor for spontaneous resolution of VMT in young healthy adults. PMID- 17726226 TI - The combination of homozygous MTHFR 677T and angiotensin II type-1 receptor 1166C variants confers the risk of small-vessel-associated ischemic stroke. AB - Previous studies have suggested that both angiotensin II type-1 receptor (AT1R) 1166C and methylenetetrahydrofolate reductase (MTHFR) 677T variants can have disadvantageous effects on the small-vessel circulation under certain conditions. The purpose of this study was to analyze the possible consequences of the simultaneous distribution of these two genetic variants in different types of ischemic stroke. The genetic and clinical data on 357 ischemic stroke patients and 263 control subjects were analyzed by using univariate and logistic statistical approaches. Neither the MTHFR 677T nor the AT1R 1166C genetic variant alone conferred the risk of any subtype of ischemic stroke. The combination of the homozygous MTHFR 677TT genotype and at least one AT1R 1166C allele occurred more frequently in the ischemic stroke patients (8.68%) than in the controls (4.56%, p < 0.05). Specific subclassification of the patients revealed an accumulation of this combination in small-vessel-associated ischemic stroke (12.2%, p < 0.01); multivariate logistic regression analysis of the data confirmed this association, with an odds ratio of 2.66 (95% confidence interval, 1.28-7.89; p < 0.05). These findings suggest that the combination of these two genetic factors can contribute to the development of small-vessel cerebral infarcts. Although the exact mechanism of action is not known, addition of the unfavourable effects on the endothelial function can be presumed. PMID- 17726227 TI - Targeting cytokine expression in glial cells by cellular delivery of an NF-kappaB decoy. AB - Inhibition of nuclear factor (NF)-kappaB has emerged as an important strategy for design of anti-inflammatory therapies. In neurodegenerative disorders like Alzheimer's disease, inflammatory reactions mediated by glial cells are believed to promote disease progression. Here, we report that uptake of a double-stranded oligonucleotide NF-kappaB decoy in rat primary glial cells is clearly facilitated by noncovalent binding to a cell-penetrating peptide, transportan 10, via a complementary peptide nucleic acid (PNA) sequence. Fluorescently labeled oligonucleotide decoy was detected in the cells within 1 h only when cells were incubated with the decoy in the presence of cell-penetrating peptide. Cellular delivery of the decoy also inhibited effects induced by a neurotoxic fragment of the Alzheimer beta-amyloid peptide in the presence of the inflammatory cytokine interleukin (IL)-1beta. Pretreatment of the cells with the complex formed by the decoy and the cell-penetrating peptide-PNA resulted in 80% and 50% inhibition of the NF-kappaB binding activity and IL-6 mRNA expression, respectively. PMID- 17726225 TI - Blockage of VIP during mouse embryogenesis modifies adult behavior and results in permanent changes in brain chemistry. AB - Vasoactive intestinal peptide (VIP) regulates growth and development during the early postimplantation period of mouse embryogenesis. Blockage of VIP with a VIP antagonist during this period results in growth restriction, microcephaly, and developmental delays. Similar treatment of neonatal rodents also causes developmental delays and impaired diurnal rhythms, and the adult brains of these animals exhibit neuronal dystrophy and increased VIP binding. These data suggest that blockage of VIP during the development of the nervous system can result in permanent changes to the brain. In the current study, pregnant mice were treated with a VIP antagonist during embryonic days 8 through 10. The adult male offspring were examined in tests of novelty, paired activity, and social recognition. Brain tissue was examined for several measures of chemistry and gene expression of VIP and related compounds. Glial cells from the cortex of treated newborn mice were plated with neurons and examined for VIP binding and their ability to enhance neuronal survival. Treated adult male mice exhibited increased anxiety-like behavior and deficits in social behavior. Brain tissue exhibited regionally specific changes in VIP chemistry and a trend toward increased gene expression of VIP and related compounds that reached statistical significance in the VIP receptor, VPAC-1, in the female cortex. When compared to control astrocytes, astrocytes from treated cerebral cortex produced further increases in neuronal survival with excess synaptic connections and reduced VIP binding. In conclusion, impaired VIP activity during mouse embryogenesis resulted in permanent changes to both adult brain chemistry/cell biology and behavior with aspects of autism-like social deficits. PMID- 17726228 TI - Meta-analysis of 12 genomic studies in bipolar disorder. AB - Multiple genome-wide expression studies of bipolar disorder have been published. However, a unified picture of the genomic basis for the disease has not yet emerged. Genes identified in one study often fail to be identified in other studies, prompting the question of whether microarray studies in the brain are inherently unreliable. To answer this question, we performed a meta-analysis of 12 microarray studies of bipolar disorder. These studies included >500 individual array samples, on a range of microarray platforms and brain regions. Although we confirmed that individual studies showed some differences in results, clear and striking regulation patterns emerged across the studies. These patterns were found at the individual gene level, at the functional level, and at the broader pathway level. The patterns were generally found to be reproducible across platform and region, and were highly statistically significant. We show that the seeming discordance between the studies was primarily a result of the following factors, which are also typical for other brain array studies: (1) Sample sizes were, in retrospect, too small; (2) criteria were at once too restrictive (generally focusing on fold changes >1.5) and too broad (generally using p < 0.05 or p < 0.01 as criteria for significance); and (3) statistical adjustments were not consistently applied for confounders. In addition to these general conclusions, we also summarize the primary biological findings of the meta analysis, focusing on areas that confirm previous research and also on novel findings. PMID- 17726230 TI - Small chicken growth hormone (scGH) variant in the neural retina. AB - A novel variant of chicken growth hormone (cGH) that is severely truncated has recently been discovered in the neural retina. It is, however, unknown whether this protein binds to GH receptors (GHRs) and has biological activity. This possibility has therefore been addressed by homology modeling, using human (h)GH as a template because it is the only GH molecule with a crystal structure and because hGH binds to cGH receptors (cGHRs). Most of the residues of the small (s)cGH model fitted the hGH template, apart from two restricted regions from Ser 12 to Gln 20 and from Ser 55 to Val 58. The scGH model differs, however, from hGH in structure: hGH is composed of a four-helix bundle, whereas scGH has three main helices. Helices 2, 3, and 4 of hGH correspond to helices 1, 2, and 3 of scGH, but they are longer by one, four, and one residues, respectively. The secondary structure of the C-terminus of scGH is therefore similar to C-terminal hGH. The N terminus of scGH is, however, severely truncated, lacking the residues of the full-length molecule derived from exons 1, 2, and 3. The N-terminus of scGH also includes 20 residues derived from intron C of full-length cGH. The predicted structure of its N-terminus has no classical secondary structure (alpha-helix or beta-sheet), whereas the N-terminus of hGH is composed of helix 1 and two mini helices located between helix 1 and 2. This difference in ribbon structure results in a difference in the overall shape of the scGH model and hGH. The possibility that scGH could bind to a GHR dimer was assessed by examining the primary and hypothetical tertiary structure of scGH. hGH binds the extracellular domain (ECD) of two GHRs sequentially at its binding site 1 (or high affinity site) then at its binding site 2 (or low affinity site). Sequence alignment of scGH with hGH demonstrates that scGH lacks three key residues (of 14) at site 1 and nine residues (of 15) at site 2. It is therefore unlikely that tight binding of ECD1 to the site 1 of scGH could occur. scGH also lacks most of the site 2 residues, suggesting that it is unlikely that ECD2 would bind to the scGH model. In summary, we have developed a novel, structural model of scGH, with implications for its putative actions through classical GHRs. PMID- 17726229 TI - Lipopolysaccharide modulation of thyrotropin-releasing hormone (TRH) and TRH-like peptide levels in rat brain and endocrine organs. AB - Lipopolysaccharide (LPS) is a proinflammatory and depressogenic agent whereas thyrotropin-releasing hormone (TRH; pGlu-His-Pro-NH2) is an endogenous antidepressant and neuroprotective peptide. LPS and TRH also have opposing effects on K+ channel conductivity. We hypothesized that LPS can modulate the expression and release of not only TRH but also TRH-like peptides with the general structure pGlu-X-Pro-NH2, where "X" can be any amino acid residue. The response might be "homeostatic," that is, LPS might increase TRH and TRH-like peptide release, thereby moderating the cell damaging effects of this bacterial cell wall constituent. On the other hand, LPS might impair the synthesis and release of these neuropeptides, thus facilitating the induction of early response genes, cytokines, and other downstream biochemical changes that contribute to the "sickness syndrome." Sprague-Dawley rats (300 g) received a single intraperitoneal injection of 100 microg/kg LPS. Animals were then decapitated 0, 2, 4, 8, and 24 h later. Serum cytokines and corticosterone peaked 2 h after intraperitoneal LPS along with a transient decrease in serum T3. TRH and TRH-like peptides were measured by a combination of high-performance liquid chromatography and radioimmunoassay. TRH declined in the nucleus accumbens and amygdala in a manner consistent with LPS-accelerated release and degradation. Various TRH-like peptide levels increased at 2 h in the anterior cingulate, hippocampus, striatum, entorhinal cortex, posterior cingulate, and cerebellum, indicating decreased release and clearance of these peptides. These brain regions are part of a neuroimmunomodulatory system that coordinates the behavioral, endocrine, and immune responses to the stresses of sickness, injury, and danger. A sustained rise in TRH levels in pancreatic beta-cells accompanied LPS-impaired insulin secretion. TRH and Leu-TRH in prostate and TRH in epididymis remained elevated 2 24 h after intraperitoneal LPS. We conclude that these endogenous neuroprotective and antidepressant-like peptides both mediate and moderate some of the behavioral and toxic effects of LPS. PMID- 17726231 TI - Novel mutations in the NF1 gene in Czech patients with neurofibromatosis type 1. AB - Neurofibromatosis type 1 (NF1) is one of the most common inherited human disorders, with an estimated incidence of 1 per 3500 births. In most cases, the disease is caused either by mutation in the NF1 gene, or by a particular or complete deletion of the NF1 gene. The NF1 gene exhibits one of the highest mutation rates of any human disorder. In this experimental study of the NF1 gene, we screened the mutational spectrum of 22 unrelated patients from the Czech Republic using the denaturing high-performance liquid chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA) methods. We found NF1 mutations in 17 patients: 15 causal mutations were detected with the use of the DHPLC method (15/20, 75%). With the MPLA method, we also confirmed and specified two large deletions that were previously genotyped by microsatellite markers. Twelve of the above-mentioned mutations were newly found: c.1_2delATinsCC, c.1185+1G>C, c.1757_1760delCTAG, c.1642-7A>G, c.2329 T>G, c.2816delA, c.3738_3741delGTTT, c.4733 C>T, c.5220delT, c.6473_6474insGAAG, ex14_49del, ex28_49del. We present this study as a first effectual step in the routine diagnosis of the NF1 in patients from the Czech Republic. PMID- 17726232 TI - Inhibition of nitric oxide synthase and farnesyltransferase change the activities of several transcription factors. AB - Several types of cellular proteins can be modified by farnesylation and nitrosylation, of which the most significant is Ras. We used manumycin, a farnesyltransferase inhibitor, and L-NAME (Nomega-nitro-L-arginine methyl ester), a nitric oxide synthase (NOS) inhibitor, for characterization of Ras-dependent downstream targets activities. Our results suggest that change of the steady state levels of nitric oxide and inhibition of farnesylation modified the activities of several transcription factors. We have found that the inhibition of farnesylation by manumycin decreased the DNA-binding activity of nuclear factor (NF)-kappaB, did not change the DNA-binding activities of STAT, Sp1, ATF-2, and CREB, and increased the activities of c-Fos, JunD, and c-Jun. Under such conditions, phosphorylation of Akt was decreased, whereas phosphorylation of extracellular signal-regulated kinase (ERK) was increased and phosphorylation of JNK did not change. Furthermore, our results show that reduction of intracellular concentration of nitric oxides by L-NAME increases the activities of c-Fos, ATF-2 and JunD and decreases the activities of CREB, STAT, Sp1, and c-Jun. The activities of all of these transcription factors are restored to normal levels in the presence of manumycin, suggesting that simultaneous modifications of proteins by farnesylation and nitrosylation change the direction of Ras-controlled downstream pathways. Our results provide further evidence of the significance of posttranslational modifications of Ras for the specificity of transducing cascade networks and physiological outcome. PMID- 17726233 TI - Age alters the ability of substance P to sensitize joint nociceptors in guinea pigs. AB - Pain perception is altered during senescence and it is thought that this could in part be due to changes in peripheral pain sensing processes. The present study examined the effect of substance P (SP) (10(-10)-10(-8) mol; 0.1 mL bolus close intraarterial) on knee joint afferent mechanosensitivity in young (2- to 5-mo old) and aged (17- to 36-mo-old) Dunkin-Hartley guinea pigs. Single unit electrophysiological recordings were made from knee joint primary afferent nerves in response to normal (nonnoxious) and painful (noxious) rotation of the joint. In young and old animals, local application of SP had a sensitizing effect on joint afferents in response to movements made in the normal working range of the knee. With noxious hyper-rotation of the joint, SP was able to increase afferent firing rate in young but not in old animals. These data demonstrate a lack of SP mediated sensitization of joint nociceptors during senescence and suggest a peripheral deficiency in joint nociception with respect to age. PMID- 17726235 TI - Role of DJ-1 in parkinson's disease. PMID- 17726234 TI - CaM kinase II isoforms are expressed at lower levels in brains of shiverer mutants. AB - In the mammalian brain, the hippocampus is involved in memory formation and storage and has an enriched level of Ca2+/calmodulin-dependent protein kinase type II (CaM kinase II). CaM kinase II has a number of downstream targets and is shown to play a role in memory development, axonal transport, and signaling across the synapse. The shiverer mutant mouse is a knockout lacking myelin basic protein. As a result, the axons of the central nervous system (CNS) of the shiverer have no or very thin myelin sheath, neurons in their CNS have distorted shapes, and synaptic signaling is impaired. shiverer mice develop symptoms similar to those experienced by patients with multiple sclerosis. In this study, proteins from the hippocampus, cerebellum, pons, medulla, and olfactory bulbs of shiverer and wild-type mice were extracted. Western blot analysis was used to compare the expression levels of CaM kinase II in these regions of the two types of mice. Analysis shows that at least two (50 and 58-59 kDa) of the four CaM kinase II isoforms are expressed in the brain, with one isoform (50 kDa) expressed in all regions examined. shiverer brain contains a decreased level of the two isoforms of CaM kinase II, an indication that the cognitive function of these mice might also be impaired. PMID- 17726236 TI - Transcriptomic molecular markers for screening human colon cancer in stool and tissue. AB - There is a need for sensitive and specific diagnostic molecular markers that can be used to monitor early patterns of gene expression in non-invasive exfoliated colonocytes shed in the stool, and in situ in adenoma-carcinoma epithelium of the colon. RNA-based detection methods are more comprehensive than either DNA-, protein- or methylation-based screening methods. By routinely and systematically being able to perform quantitative gene expression studies on these samples using less than ten colon cancer genes selected by the enormous resources of the National Cancer Institute's Cancer Genome Anatomy Project, we were able to monitor changes at various stages in the neoplastic process, allowing for reliable diagnostic screening of colon cancer particularly at the early, pre malignant stages. Although the expression of some of the genes tested in tissue showed less variability in normal or cancerous patients than in stool, the stool by itself is suitable for screening. Thus, a transcriptomic approach using stool or tissue samples promises to offer more sensitivity and specificity than currently used molecular screening methods for colon cancer. A larger prospective clinical study utilizing stool and tissue samples derived from many control and colon cancer patients, to allow for a statistically valid analysis, is now urgently required to determine the true sensitivity and specificity of the transcriptomic screening approach for this preventable cancer. PMID- 17726237 TI - Telomerase: a crucial player in HTLV-I-induced human T-cell leukemia. AB - One in seven types of human cancer is associated with an oncogenic virus infection. Most human tumors have high telomerase activity but very short telomeres, yet the maintenance of these short telomeres is critical to avoid telomere end fusion or senescence and to support active proliferation. Oncogenic viruses have evolved a wide repertoire of strategies to stimulate telomerase functions at the transcriptional and post-transcriptional levels. Since telomerase activity is absent in somatic cells, the inhibition of telomerase is an attractive target for cancer therapeutics. PMID- 17726238 TI - Guideline for data analysis of genomewide association studies. AB - Intensive efforts have been underway to identify common genetic factors that influence health and disease including cancer using genomewide association studies (GWAS). Our experiences have shown that while it is more advantageous to have large detailed data sets, the amount of information generated by GWAS also present major challenges for statistical analyses. While prospects for the oncoming flood of GWAS is exciting, the tools for conducting and evaluating these studies are still in early developmental stages creating some investigator uncertainty and prompting conferences and workshops specifically devoted to these topics. In this review, we summarize important steps for planning the statistical analysis involving genome-wide data from single nucleotide polymorphisms (SNPs). This review is purposely meant to be relatively short and of practical use for the space constraints of typical federal grant proposals. PMID- 17726239 TI - Low concentrations of beta-carotene stimulate the proliferation of human pancreatic duct epithelial cells in a PKA-dependent manner. AB - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is among the most common causes of cancer death. Preclinical and clinical studies on the preventive effects of beta-carotene or other retinoids have used dietary supplements that yielded high systemic concentrations (1-50 microM). While some of the preclinical data suggested cancer preventive effects of these agents, they have disappointed in clinical investigations. MATERIALS AND METHODS: The effects of low concentrations (10 fM-200 nM)of beta-carotene on the proliferation, intracellular cAMP levels, PKA activation status and phosphorylation of EGFR-specific tyrosine kinases and ERK1/2 in immortalized human pancreatic duct epithelial cells was investigated. RESULTS: Our data show significant concentration-dependent and PKA dependent stimulation of all measured endpoints. Similar responses were achieved with forskolin. Our data indicate that low concentrations of beta-carotene stimulate the proliferation of the putative origin of PDAC, pancreatic duct epithelial cells via cAMP and PKA-dependent transactivation of the EGFR pathway. This could potentially have promoting effects on the development of PDAC. PMID- 17726240 TI - Molecular mechanisms for the antitumor activity of inositol hexakisphosphate (IP6). AB - BACKGROUND: Inositol hexakisphosphate (IP6), a naturally occurring polyphosphorylated carbohydrate, has been reported to have significant in vivo and in vitro anticancer activity against numerous tumors. However, the molecular mechanism of the anticancer effect of IP6 has not been fully elucidated. MATERIALS AND METHODS: Using K-562 human leukemia cells we analysed the induction of the erythroid differentiation program, as well as modulation of the gene expression profile of K-562 leukemia cells treated with IP6. RESULTS: A single treatment with IP6 (0.75 or 5.0 mM) resulted in a time- and dose-dependent growth inhibition of K-562 cells and also activation of the erythroid differentiation program. K-562 cells expressed a concomitant differentiation after 12 hours of exposure. Possible molecular mechanisms and key signaling pathways, as well as gene expression behind this anticancer effect were examined using oligonucleotide microarrays and quantitative real-time PCR. Treatment with IP6 (750 microM, 5 mM) had a marked impact, resulting in early (60 min) and late (12 h) modulation of expression of about 1800 and 1200 transcripts (at p<0.05). Through microarray analysis, the anticancer effect of IP6 in K-562 was found to be associated with the modulation of multiple genes involved in immunity, Wnt and IGF pathways, PI3 kinase signaling and apoptosis. Using selected subsets of genes, the microarray hits could be validated by Q-PCR. A 2-fold upregulation of the apoptosis pathway, measured using the BAX/BCL-2 ratio was observed for 12 hours. IP6 (5 mM) induced up to 6-fold increases in differentiation measured by hemoglobin synthesis, yielding up to 70% of benzidine-positive cells at 120 hours. CONCLUSION: The results of this study show that IP6 is a strong inducer of differentiation (cytostatic effect) and a moderately strong inducer of apoptosis (cytotoxic effect). Evidence has been provided to show that the growth inhibitory effects of IP6 are mediated through the modulation of key signaling pathways. PMID- 17726241 TI - Movements execution in amnestic mild cognitive impairment and Alzheimer's disease. AB - We evaluated the relationship between motor and neuropsychological deficits in subjects affected by amnestic Mild Cognitive Impairment (aMCI) and early Alzheimer's Disease (AD). Kinematics of goal-directed movement of aMCI and AD subjects were compared to those of age-matched control subjects. AD showed a slowing down of motor performance compared to aMCI and controls. No relationships were found between motor and cognitive performances in both AD and aMCI. Our results suggest that the different motor behaviour between AD and aMCI cannot be related to memory deficits, probably reflecting the initial degeneration of parietal-frontal circuits for movement planning. The onset of motor dysfunction in early AD could represent the transition from aMCI to AD. PMID- 17726242 TI - Relationship between object-related gestures and the fractionated object knowledge system. AB - The praxic semantic system comprises a conceptual knowledge system, which stores functional information about objects, and an action knowledge system, which stores information about the correct manipulation of objects. Moreover, mechanical problem solving abilities permit to take advantages from objects structure to use unfamiliar tools or discover alternative ways of using familiar tools. This study aims at investigating whether conceptual knowledge, action knowledge and mechanical problem solving abilities intervene in the production of gestures with objects (i.e. pantomimes and object use) by testing a group of brain damaged patients. Results showed that the mechanical problem solving abilities are not sufficient to produce pantomimes and that only severe deficits in the praxic semantic system would affect the production of these gestures. Furthermore, a double dissociation was observed between mechanical problem solving abilities and the capacity to use multiple objects. Overall, the results indicate that the praxic semantic system can be disrupted at different levels, suggesting that the semantic system for object has to be conceived as fractionated in different entities. PMID- 17726243 TI - Characteristics and reversibility of dementia in Normal Pressure Hydrocephalus. AB - Studies of the cognitive outcome after shunt insertion for treatment of Normal Pressure Hydrocephalus have reported widely mixed results. We prospectively studied performance of 60 patients with Normal Pressure Hydrocephalus on a comprehensive battery of neuropsychological tests before and after shunt surgery to determine which cognitive functions improve with shunt insertion. We also administered a subset of cognitive tests before and after temporary controlled drainage of cerebrospinal fluid to determine if change on this brief subset of tests after drainage could predict which patients would show cognitive improvement three to six months after shunt insertion. There was a significant improvement in learning, retention, and delayed recall of verbal memory three to six months after surgery (using paired t-tests). The majority (74%) of patients showed significant improvement (by at least one standard deviation) on at least one of the memory tests. Absence of improvement on verbal memory after temporary drainage of cerebrospinal fluid had a high negative predictive value for improvement on memory tests at 3-6 months after surgery (96%; p=0.0005). Also, the magnitude of improvement from Baseline to Post-Drainage on few specific tests of learning and recall significantly predicted the magnitude of improvement after shunt surgery on the same tests (r2=0.32-0.58; p=0.04-0.001). Results indicate that testing before and after temporary drainage may be useful in predicting which patients are less likely to improve in memory with shunting. PMID- 17726244 TI - The clinical overlap between the corticobasal degeneration syndrome and other diseases of the frontotemporal spectrum: three case reports. AB - The corticobasal degeneration syndrome has been suggested to be part of a complex of conditions (including the different subtypes of frontotemporal dementia and progressive supranuclear palsy), which reflect a spectrum of pathological substrates. This concept is supported by the frequent clinical overlap that can be observed among patients diagnosed with these conditions. We report three clinical cases, characterized by the overlap of the clinical features of corticobasal degeneration syndrome with, respectively, nonfluent progressive aphasia, progressive supranuclear palsy and semantic dementia. Current diagnostic criteria emphasize differences in clinical presentation, which probably reflect the preferential location of pathology in the early stages of disease. However, with disease progression, a considerable clinical overlap can be expected among the different syndromes. This concept should be extended not only to the cognitive and behavioural features of the frontotemporal dementia subtypes, but also to the movement disorders of corticobasal degeneration and supranuclear palsy. PMID- 17726245 TI - Comparison of motor activity and sleep in patients with complex partial seizures on levetiracetam treatment and a group of healthy subjects. AB - PURPOSE: Levetiracetam-treated patients commonly report daytime drowsiness, fatique, asthenia and decreasing of motor activity. However the origin of these reported side effects are still debated, we aimed to clarify effect of levetiracetam on sleep. Therefore this prospective study was conducted to evaluate the effects of levetiracetam on motor activity, amount and continuity of sleep and napping. METHODS: Various tests were performed on twenty two patients treated with levetiracetam (10 monotherapy, 12 add-on therapy) at least three days before the initiation of treatment, and consecutively for five to eight days at the third week of treatment. These tests included sleep logs, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Modified Maintenance of Wakefulness Test and actimetric measurements. In order to evaluate the sleep behavior of these patients the following sleep parameters were estimated: bedtime, wake-up time, sleep-onset time, sleep-offset time, sleep latency, total sleep time, wake time after sleep onset, fragmentation index, total activity score, nap episodes, total nap duration and sleep efficiency. Twenty members of staff from our hospital (Doctor, nurse, secretary, civil servant etc.) were evaluated as control subjects in the study. RESULTS: After three-week treatment with levetiracetam (in particular with add-on therapy), Epworth Sleepiness Scale scores, napping episodes and total nap durations increased and sleep latencies decreased. While durations of Modified Maintenance of Wakefulness Test and total activity scores decreased. However the total sleep time and the sleep efficiency did not show any difference from the pre-treatment values. CONCLUSIONS: Our results suggest that levetiracetam leads to drowsiness by decreasing the daily motor activity and increasing the naps; however this agent does not have any major effects on total sleep time and sleep efficiency during night. Actimetric analyses give information about continuity of sleep and sleep/wake states however does not give satisfactory information about architecture of sleep. In order to determine the effects of levetiracetam on the sleep architecture we need similiar protocol studies by full night polysomnography. PMID- 17726246 TI - Neurological abnormalities in Chinese schizophrenic patients. AB - BACKGROUND: This study attempted to examine the prevalence and type of neurological signs in Chinese patients with schizophrenia. METHODS: A cross sectional design was adopted with the use of the Cambridge Neurological Inventory (CNI). The CNI is comprised of 7 subscales, including motor coordination, sensory integration, disinhibition, extrapyramidal signs, dyskinesia, catatonia, and pyramidal signs. The former 3 subscales were classified as soft signs, whereas the latter 4 subscales were classified as hard signs. A total of 250 Chinese schizophrenic patients and 90 normal controls were recruited. RESULTS: Patients exhibited significantly more signs than normal controls in all subscales but pyramidal signs (p < 0.00005). Significant differences were also found in total soft signs, total hard signs as well as total neurological signs (p < 0.0005). The three subscales of soft signs showed a relatively better sensitivity and specificity as compared with the four subscales of hard signs. Improvement in sensitivity and specificity was demonstrated when the subscales were collapsed into total soft signs, total hard signs and total neurological signs. A cut-off of 4 in total soft signs yields a sensitivity of 0.63 and specificity of 0.71; whereas a cut-off of 1 in total hard signs yields a sensitivity of 0.78 and specificity of 0.89. A global cut-off of 5 in total neurological signs results in a sensitivity of 0.81 and specificity of 0.73 for detecting schizophrenia versus normal. CONCLUSIONS: High levels of neurological abnormality characterize schizophrenic patients. An extended assessment battery of CNI provides even better discrimination of patients from normal controls, and soft signs are more strongly associated with schizophrenia than are hard signs in the Chinese sample. PMID- 17726247 TI - Anton's syndrome following callosal disconnection. AB - Anosognosia for cortical blindness, also called Anton's syndrome, is a rare neurological disorder usually following bilateral lesions to occipital cortices. Neuropsychological, morphological and functional neuroimaging (SPECT and fMRI) findings are reported in a patient who incurred Anton's syndrome after an ischaemic lesion confined to the left occipital lobe involving the corpus callosum. The present case study suggests that Anton's syndrome may also follow from lesions disconnecting the occipital cortices. PMID- 17726248 TI - Persistent visual aura following catheter ablation in a patient with WPW syndrome. AB - We report a patient who has had persistent visual disturbances since she underwent catheter ablation to treat her Wolff-Parkinson-White (WPW) syndrome. We examined her visual symptoms carefully and quantitatively by means of our newly developed method combining image-processing and psychophysics. We first simulated the patient's visual symptoms using image-processing techniques. Since the simulation indicated that she would be very sensitive to the edges of the visual stimuli, we evaluated her sensitivity to the edges using psychophysics. The results indicated that she was hypersensitive to the clear-cut edges of the visual stimuli. Her visual symptoms were very similar to those of visual aura of migraine, rather than those of photosensitive epilepsy. Magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT), electroenchepalogram (EEG), and visual-evoked potentials (VEP) in the patient were normal. No abnormalities in her fundus, visual field, or electroretinogram were found, either. Transesophageal echocardiography with bubble study indicated that she had a preexisting right-to-left shunt. We hypothesize that visual aura of migraine was triggered and made persistent by the catheter ablation in this patient. Although the relationship between migraine, catheter ablation, and right to-left shunts is unknown, previous studies on the transcatheter closure of patent foramen ovale suggest a possible link between them. Catheter ablation in patients with migraine and preexisting shunts may lead to exacerbations in migraine symptoms. PMID- 17726249 TI - De Clerambault's syndrome (erotomania) as a presenting feature of fronto-temporal dementia and motor neurone disease (FTD-MND). PMID- 17726250 TI - The rheological changes after cesarean section: The influence of low molecular weight or unfractionated heparin on the rheological properties of blood. AB - Thromboembolic complications remain an important cause of maternal mortality. The present recommendations favour for prophylaxis unfractionated (UFH) and low molecular weight heparin (LMWH). We investigated 150 pregnant women before and after cesarean section in three randomized groups. Fifty women received no prophylaxis (group I), 50 women UFH two times 5000 IU/day (group III) and 50 women Dalteparin 5000 U/day (group II). We determined the blood count, the rheological parameters and cholesterol, triglycerides, D-dimer, fibrinogen and the anti-Xa-level. We found a classical hemodilution, with increase of erythrocyte aggregation and plasma viscosity postoperatively. The fibrinogen turnover and D-dimer concentration were elevated. The patients with Dalteparin prophylaxis showed lower thrombin activation, minor changes in the cholesterol and triglycerides level and an improvement of red cell deformability in low shear regions. Our results demonstrated an influence of Dalteparin on the rheological parameters post surgery. The DVT incidence was 1.33% generally and occurred only in the Control group and in women with unfractionated heparin. We observed no side effects such as major bleeding, osteopenia or allergy. PMID- 17726251 TI - Erythrocyte deformability in obesity measured by ektacytometric techniques. AB - Erythrocyte deformability (ED) has been scarcely evaluated in obese patients without other concomitant cardiovascular risk factors and contradictory results have been published regarding the influence of plasma lipids on the erythrocyte membrane lipid composition and insulin resistance on this rheological parameter. In 67 severe or morbid obese patients without other cardiovascular risk factors (51 women and 11 men, aged 34+/-11 years) and in 67 controls (45 women and 22 men, aged 32+/-10 years), ED has been determined by ektacytometric techniques in a Rheodyn SSD, the elongation index (EI) being measured at 12, 30 and 60 Pa, along with plasma lipids, red blood cell membrane lipids (cholesterol and phospholipids) and insulin resistance indexes in basal conditions and after a three month diet period. No significant differences were obtained in the EI between obese patients and the control group at any of the shear stresses tested (P>0.05). The cholesterol and phospholipid content of the red blood cell membrane did not significantly differ between cases and controls (P>0.05). Obese patients with metabolic syndrome showed lower EI at 30 and 60 Pa than those without metabolic syndrome (P=0.014 and P=0.031 respectively). Weight loss was not accompanied by any changes in these rheological parameters. Obesity itself does not seem to modify ED. However, metabolic syndrome seems to decrease ED, possibly through insulin resistance. PMID- 17726252 TI - Microvascular periodontal alterations: A possible relationship between periodontitis and rheumatoid arthritis. AB - BACKGROUND: Microvascular involvements represent one of the first steps in many autoimmune diseases such as rheumatoid arthritis (RA). The aim of this study was to investigate the differences in periodontal microcirculation between healthy subjects and patients suffering from RA. METHODS: Thirty healthy subjects and 30 patients suffering from RA were examined. The patients who showed conditions known to compromise microcirculation, such as diabetes, hypertension, pharmacological treatments, were not included in the group of healthy patients. All the patients were non-smokers. Periodontal capillaroscopy was used to investigate the characteristics of microcirculation. Visibility, course, tortuosity, as well as the possible presence of microhemorrhages, the average caliber of the capillary loops and the number of visible capillary loops per square millimeter were evaluated for each patient. RESULTS: Microcirculation architecture in the healthy and in the RA patients was characterized by a network of capillaries in polygonal mesh with parallel orientation as regards the surface. In patients suffering from RA, it was possible to observe a reduced caliber of capillaries, as well as a greater number and elongated capillaries. No significant differences relating to oral capillaroscopic pattern were detected between RA patients that were rheumatoid factor, ANA, RANA positive and RA patients that were rheumatoid factor, ANA, RANA negative. CONCLUSIONS: This study shows that capillary alterations in patients suffering from RA occur in periodontal microcirculation; such evidence could be extremely important, suggesting that microvascular periodontal alterations may play a crucial part in the complex activity associated with periodontal disease in AR patients. PMID- 17726253 TI - Influence of fatty acid composition in mammalian erythrocytes on cellular aggregation. AB - The rheologic properties of red blood cells (RBC) are determined by humoral and cellular factors. Fatty acid composition of the RBC phospholipid bilayer is one factor influencing membrane fluidity this could affect RBC aggregation because of a higher bias of RBC deformability. The present investigation was performed to investigate a possible relationship between fatty acid composition and erythrocyte aggregation using animals with high RBC aggregation (horse and pig) and animals with immeasurable RBC aggregation (sheep). Horse and pig showed similar distribution of the four major components palmitoleic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1n9), and linoleic acid (C18:2n6). The sheep's saturated fatty acids C16:0 and C18:0 were decreased, whereas unsaturated oleic acid (C18:1n9) showed a two fold increase in comparison to horse and pig. It can be assumed that the fatty acid bilayer is a minor factor influencing erythrocyte flexibility due to its influence on membrane fluidity and therefore there might be an existing link to erythrocyte aggregation. The sheep has relatively dense erythrocytes with low cell volumes. Therefore, the absence of aggregation might be postulated to arise from geometric factors against the expected effect of unsaturated fatty acids on membrane fluidity, the higher level of unsaturated fatty acids in ovine erythrocytes over that found in horse and pig was surprising. The present result, which accords with former studies, indicates that the geometric factor given by the intracellular skeleton overrides any effect of membrane composition on aggregation in sheep. PMID- 17726254 TI - Acute training in racing horses at two different levels of effort: A haemorheological analysis. AB - During acute exercise several significant cardiovascular alterations take place, along with possible physiopathological consequences, such as Exercise Inducted Pulmonary Haemorrhage (EIPH). Given the relevance of blood rheology in the determination of flow resistance and its supposed participation in the stated events, the present paper focuses on the analysis of modifications in haematocrit, blood viscosity and erythrocyte deformability in Thoroughbred horses caused by two different levels of effort (6 to 9 m/s and 13 to 16 m/s), in the same track they train in and with their own jockeys. The results obtained show a deep modification in those parameters, as consequence of the exercise. However, no significant discrepancies were observed between the different levels of effort in which the training was performed. PMID- 17726255 TI - Dissociated effects of physical activity and weight loss on fibrinogen concentrations and markers of red blood cell aggregation. Relevance for life style modification in atherothrombosis. AB - It has been shown that weight loss and physical activity contribute to a better biorheological profile. Yet, the concentrations of fibrinogen are not always reduced following life style modification. We evaluated the inter-relations between fibrinogen's pro red cell aggregation potential and reduced inflammation and improved lipid profile as anti-aggregating forces in a group of 20 apparently healthy obese volunteers following 4 and 8 months of intensive life modification program which included diet and strenuous physical activity. A significant (p=0.005) weight loss (from a mean+/-SD of 121.4+/-20.9 to 98.0+/-21.3 kg) and decrease in body mass index (from 40.8+/-4.3 to 32.9+/-5.3 kg/m(2), p=0.005) was noted in fourteen individuals who completed the 8-month program. The concentrations of clottable fibrinogen rose from 318+/-96 to 387+/-72 mg/dl (p=0.012) while there was a significant reduction in the erythrocyte sedimentation rate (ESR) (from 19.0+/-12.6 to 10.8+/-7.5 mm/h, p=0.018), triglycerides (from 143+/-80 to 80+/-44 mg/dl, p=0.005), LDL cholesterol (from 128+/-34 to 103+/-17 mg/dl, p=0.005) and total cholesterol (from 211+/-40 to 171+/-17 mg/dl, p=0.007), as well as decrease in insulin concentration (from 36.1+/-21.3 to 20.6+/-8.0 microu/ml, p=0.01) and the insulin resistance index (HOMA-R, from 9.1+/-6.4 to 4.9+/-2.1 glu*ins/405, p=0.008). Despite a significant increment in the concentrations of clottable fibrinogen, a significant reduction was noted in the degree of red cell aggregation as measured by using a slide test and direct visualization of the aggregates. Our conclusion is that the pro aggregating properties of fibrinogen following intense physical activity are probable counterbalanced by the anti-aggregatory properties of an improved lipid profile and an attenuated acute phase response. PMID- 17726256 TI - Erythrocyte deformability in anaemic patients with reticulocytosis determined by means of ektacytometry techniques. AB - It is not clearly established whether reticulocyte deformability is lower than that of the mature erythrocytes, as most of studies published on this matter have evaluated this rheological parameter by means of micropipette techniques, which are unsuitable for routine measurements. Information is scarce as regards the evaluation of reticulocyte deformability by means of ektacytometry techniques, routinely used in clinical laboratories. We aimed to evaluate erythrocyte deformability (ED), with ektacytometry, in samples of 44 anaemic patients with peripheral reticulocytosis (reticulocytes: (260+/-150)x10(3)/microl) and in 60 healthy non-anaemic volunteers with a normal reticulocyte count (reticulocytes: (60+/-20)x10(3)/microl). We also determined other factors that may influence ED, such as erythrocyte indices (MCV, MCH, MCHC), glucose, total cholesterol and triglycerides. ED was evaluated determining the elongation indices (EI) at 12, 30 and 60 Pa, by means of the Rheodyn SSD. At the three shear stresses tested, patients showed statistically lower EI than controls, higher reticulocyte count, lower cholesterol levels and higher MCHC (P<0.001, respectively). A statistically significant negative correlation (P<0.01) was found between the reticulocyte count and the EI at 12, 30 and 60 Pa (r=-0.643, r=-0.678 and r=-0.692, respectively), and between the EI and the MCHC (correlation coefficients: -0.743, -0.741 and -0.738; P<0.01). As the differences in ED could be attributed partly to alterations in erythrocyte indices and plasma lipid levels, a linear regression analysis was performed, showing that EI is independently associated with the reticulocyte count. Our results suggest that reticulocytes are responsible for the decreased ED observed in anaemic patients with peripheral reticulocytosis, when this hemorheological parameter is evaluated by means of ektacytometry techniques. PMID- 17726258 TI - Leukocyte involvement in the signs and symptoms of chronic venous disease. Perspectives for therapy. AB - Pain intensity in chronic venous disease varies with the stage in the clinical etiologic-anatomic-pathophysiologic (CEAP) classification but also with patient perception, pain being by definition subjective. The venous hypertension responsible for the varicose veins and trophic changes in CVD has a variety of algogenic repercussions in which leukocytes play a particular role, notably through their ability to roll along the vessel wall. Shear stress, hypoxia and stasis activate the marginated leukocytes to shed L-selectin from their surface and express integrins, matrix metalloproteinase 9, elastase, lactoferrin and free radicals. Meanwhile the endothelium expresses adhesion molecules that permit slow rolling on E-selectin followed by adhesion and tissue transmigration. Vein wall and valve areas in particular attract mast cells, monocyte-macrophages and T lymphocytes, and undergo remodeling. Sympathetic sensory C and Adelta fibers, which wrap around cutaneous venules and are also present in the venous intima and media, are nociceptors sensitive to the pain mediators concentrated within leukocytes, such as mast cell bradykinin, responsible for visceral pain. Neuronal inflammation combined with wall remodeling intensifies symptoms. Yet no direct link has so far been shown between pain and mast cell mediator levels. Leukocyte adhesion is also associated with the increased capillary permeability that leads to edema. Antileukocyte therapies include postural rest and venotonics which alone or in combination with compression have been shown to unstick and inhibit leukocytes. The micronized purified flavonoid fraction (MPFF) protects vascular endothelium against hypoxia and reduces adhesion molecule expression. Unlike other antileukocyte therapies, venotonics do not cause neutropenia. PMID- 17726257 TI - Changes of asymmetric dimethylarginine, nitric oxide, tetrahydrobiopterin, and oxidative stress in patients with acute myocardial infarction by medical treatments. AB - The relationship among the nitric oxide synthase (NOS) inhibitor [asymmetric dimethylarginine (ADMA)], NOS cofactor [tetrahydrobiopterin (BH(4))], and superoxide anion in the patients with acute myocardial infarction (AMI) is still unknown. This study sought to assess the NOS inhibitor and cofactor with oxidative stress in AMI patients (n=9) during initial administration and 4 weeks after medical treatments. We measured plasma NOS inhibitor and cofactor (ADMA and BH(4)) by HPLC and plasma oxidized-LDL by ELISA. Blood samples from age-matched healthy volunteers (n=9) were taken for comparison. In AMI, plasma ADMA, oxidized BH(4) (BH(2)+biopterin) and oxidized-LDL significantly increased (P<0.0001, P<0.01 and P<0.05 vs. healthy volunteers) and plasma BH(4), plasma nitrate and L arginine/ADMA significantly decreased compared with healthy volunteers (P<0.0001, P<0.05 and P<0.005 vs. healthy volunteers). Medical treatments improved plasma ADMA, nitrate, BH(4) and oxidized-LDL. In conclusion, ADMA increased, and NO and BH(4) decreased with oxidative stress in AMI, and these mediators improved in AMI patients with medical treatments. These findings indicated that inhibition of NOS with oxidative stress plays a crucial role in endothelial dysfunction in patients with AMI. PMID- 17726259 TI - Intratumor genetic heterogeneity of breast carcinomas as determined by fine needle aspiration and TaqMan low density array. AB - BACKGROUND: Gene expression profiling is thought to be an important tool in determining treatment strategies for breast cancer patients. Tissues for such analysis may at a preoperative stage be obtained, by fine needle aspiration (FNA) allowing initiation of neoadjuvant treatment. To evaluate the extent of the genetic heterogeneity within primary breast carcinomas, we examined whether a gene expression profile obtained by FNA was representative of the tumor. METHODS: Tumors from 12 consecutive cases of early predominantly estrogen receptor positive (ER+) breast cancer patients undergoing primary surgery were split in halves and FNAs were obtained from each half. A tissue biopsy of the tumors was also snap-frozen for comparison. Non-amplified RNA was investigated by the novel qRT-PCR-based technique, Low Density Array (LDA) using 4 reference genes and 44 target genes. RESULTS: Comparison of gene expression at the single gene level in the two FNA samples from each tumor demonstrated various degrees of heterogeneity. However, compared as gene expression profiles, intratumor correlations for 9/12 patients were high and these pairs could in a theoretical blinding of all the FNAs be correctly matched by statistical analysis. High correlations between the gene profiles of tumor FNAs and tissue biopsies from the same patient were observed for all patients. A cluster analysis identified clustering of both the two FNAs and the tissue biopsy of the same 9 patients. CONCLUSION: The overall genetic heterogeneity of breast carcinomas, as sampled by FNA, does not prohibit generation of useful gene profiles for treatment decision making. However, sampling and analysis strategies should take heterogeneity within a tumor, and varying heterogeneity amongst the single genes, into account. PMID- 17726260 TI - Expression of integrin alpha10 is induced in malignant melanoma. AB - Recently, integrin alpha10 was described as a collagen type II-binding integrin expressed mainly in chondrocytes. However, by array studies we detected integrin alpha10 also to be upregulated in malignant melanoma compared to primary melanocytes. Subsequent analysis of melanoma cell lines and melanoma tumor samples confirmed this finding. Further, we demonstrated that expression of integrin alpha10 is controlled by AP-2 and Ets-1, two transcription factors known to be involved in melanoma development and progression. To investigate the functional relevance of integrin alpha10, expression was downregulated via stable antisense transfection. Proliferation assays and colony forming assays revealed no differences comparing antisense integrin alpha10 cell clones with control and wild type melanoma cells, respectively. However, antisense integrin alpha10 cell clones and Mel Im cells treated with an inhibitory antibody against integrin alpha10 showed a reduced migratory potential. In summary, these data indicate that AP-2 and Ets-1 regulated expression of integrin alpha10 plays a role in migration of malignant melanoma cells. PMID- 17726261 TI - The carcinoma-stromal ratio of colon carcinoma is an independent factor for survival compared to lymph node status and tumor stage. AB - BACKGROUND: Tumor staging insufficiently discriminates between colon cancer patients with poor and better prognosis. We have evaluated, for the primary tumor, if the carcinoma-percentage (CP), as a derivative from the carcinoma stromal ratio, can be applied as a candidate marker to identify patients for adjuvant therapy. METHODS: In a retrospective study of 63 patients with colon cancer (stage I-III, 1990-2001) the carcinoma-percentage of the primary tumor was estimated on routine H&E stained histological sections. Additionally these findings were validated in a second independent study of 59 patients (stage I III, 1980-1992). (None of the patients had received preoperative chemo- or radiation therapy nor adjuvant chemotherapy.) RESULTS: Of 122 analyzed patients 33 (27.0%) had a low CP and 89 (73.0%) a high CP. The analysis of mean survival revealed: overall-survival (OS) 2.13 years, disease-free- survival (DFS) 1.51 years for CP-low and OS 7.36 years, DFS 6.89 years for CP-high. Five-year survival rates for CP-low versus CP-high were respectively for OS: 15.2% and 73.0% and for DFS: 12.1% and 67.4%. High levels of significance were found (OS p<0.0001, DFS p<0.0001) with hazard ratio's of 3.73 and 4.18. In a multivariate Cox regression analysis, CP remained an independent variable when adjusted for either stage or for tumor status and lymph-node status (OS p<0.001, OS p<0.001). CONCLUSIONS: The carcinoma-percentage in primary colon cancer is a factor to discriminate between patients with a poor and a better outcome of disease. This parameter is already available upon routine histological investigation and can, in addition to the TNM classification, be a candidate marker to further stratify into more individual risk groups. PMID- 17726262 TI - Molecular alterations of KIT oncogene in gliomas. AB - Gliomas are the most common and devastating primary brain tumours. Despite therapeutic advances, the majority of gliomas do not respond either to chemo or radiotherapy. KIT, a class III receptor tyrosine kinase (RTK), is frequently involved in tumourigenic processes. Currently, KIT constitutes an attractive therapeutic target. In the present study we assessed the frequency of KIT overexpression in gliomas and investigated the genetic mechanisms underlying KIT overexpression. KIT (CD117) immunohistochemistry was performed in a series of 179 gliomas of various grades. KIT activating gene mutations (exons 9, 11, 13 and 17) and gene amplification analysis, as defined by chromogenic in situ hybridization (CISH) and quantitative real-time PCR (qRT-PCR) were performed in CD117 positive cases. Tumour cell immunopositivity was detected in 15.6% (28/179) of cases, namely in 25% (1/4) of pilocytic astrocytomas, 25% (5/20) of diffuse astrocytomas, 20% (1/5) of anaplastic astrocytomas, 19.5% (15/77) of glioblastomas and one third (3/9) of anaplastic oligoastrocytomas. Only 5.7% (2/35) of anaplastic oligodendrogliomas showed CD117 immunoreactivity. No association was found between tumour CD117 overexpression and patient survival. In addition, we also observed CD117 overexpression in endothelial cells, which varied from 0-22.2% of cases, being more frequent in high-grade lesions. No KIT activating mutations were identified. Interestingly, CISH and/or qRT-PCR analysis revealed the presence of KIT gene amplification in 6 glioblastomas and 2 anaplastic oligoastrocytomas, corresponding to 33% (8/24) of CD117 positive cases. In conclusion, our results demonstrate that KIT gene amplification rather than gene mutation is a common genetic mechanism underlying KIT expression in subset of malignant gliomas. Further studies are warranted to determine whether glioma patients exhibiting KIT overexpression and KIT gene amplification may benefit from therapy with anti-KIT RTK inhibitors. PMID- 17726263 TI - Independent induction of caspase-8 and cFLIP expression during colorectal carcinogenesis in sporadic and HNPCC adenomas and carcinomas. AB - BACKGROUND: TNF-Related Apoptosis Inducing Ligand (TRAIL) is a promising agent for the induction of apoptosis in neoplastic tissues. Important determinants of TRAIL sensitivity are two intracellular proteins of the TRAIL pathway, caspase-8 and its anti-apoptotic competitor cellular Flice-Like Inhibitory Protein (cFLIP). METHODS: The aim of this study was to investigate basic expression of caspase-8 and cFLIP in normal colorectal epithelium (n=20), colorectal adenomas (n=66) and colorectal carcinomas (n=44) using immunohistochemistry performed on both sporadic and Hereditary Non-Polyposis Colorectal Cancer (HNPCC or Lynch syndrome) associated adenomas and carcinomas. RESULTS: Expression of both caspase-8 and cFLIP was similar in cases with sporadic and hereditary origin. Expression of caspase-8 in colorectal adenomas and carcinomas was increased when compared to normal colon tissue (P=0.02). Nuclear, paranuclear as well as cytoplasmic localizations of caspase-8 were detected. Immunohistochemistry revealed an upregulation of cFLIP in colorectal carcinomas in comparison to normal epithelium and colorectal adenomas (P<0.001). A large variation in the caspase-8/cFLIP ratio was observed between the individual adenomas and carcinomas. CONCLUSION: Caspase 8 and cFLIP are upregulated during colorectal carcinogenesis. Upregulation of caspase-8 and/or downregulation of cFLIP may be interesting approaches to maximize TRAIL sensitivity in colorectal neoplasms. PMID- 17726264 TI - Overexpression of gastrin-releasing peptide receptors in tumor-associated blood vessels of human ovarian neoplasms. AB - BACKGROUND: Peptide receptors, overexpressed in specific cancers, represent new diagnostic and therapeutic targets. In this study, receptors for the gastrin releasing peptide (GRP), and other members of the bombesin-family of peptides, were evaluated in ovarian neoplasms. METHODS: 75 primary, secondary and metastatic ovarian tumors were investigated for their bombesin-receptor subtype expression, incidence, localization and density using in vitro autoradiography on tissue sections with the universal radioligand (125)I-[D-Tyr(6), beta-Ala(11), Phe(13), Nle(14)]-bombesin(6-14) and the GRP-receptor subtype-preferring (125)I [Tyr(4)]-bombesin. RESULTS: GRP-receptors were detected in 42/61 primary ovarian tumors; other bombesin-receptor subtypes (BB1, bb3) were rarely present (3/61). Two different tissue compartments expressed GRP-receptors: the tumoral vasculature was the predominant site of GRP-receptor expression (38/61), whereas neoplastic cells more rarely expressed GRP-receptors (14/61). GRP-receptor positive vessels were present in the various classes of ovarian tumors; generally, malignant tumors had a higher incidence of GRP-receptor positive vessels compared to their benign counterparts. The prevalence of such vessels was particularly high in ovarian carcinomas (16/19) and their metastases (5/5). The GRP-receptors were expressed in high density in the muscular vessel wall. Normal ovary (n=10) lacked GRP-receptors. CONCLUSIONS: The large amounts of GRP receptors in ovarian tumor vessels suggest a role in tumoral vasculature and possibly angiogenesis. Further, these vessels might be targeted in vivo with bombesin analogs for diagnosis or for therapy. PMID- 17726265 TI - Cytology microarrays. AB - The use of high throughput genetic and expression platforms are generating many candidate diagnostic markers and therapeutic targets for a wide variety of clinical conditions. Tissue microarrays can be used for the evaluation of the utility of many of these markers. However, tissue microarrays can suffer from the limitations associated with sampling and sectioning tissues. We introduce a novel microarray technique based on cell suspensions. Multiple slides can be made, all of which are equally representative of the initial sample. A robotic device was designed that can deposit 60 distinct spots of cytological material on a glass slide. Each spot of cells deposited in this manner may correspond to a unique source. Controlling the number of cells per spot, their distribution within the spot and the size of the spot can be achieved by modifying the viscosity of the cell solution or regulating the amount of fluid deposited. A fully automated analysis of quantitatively stained microarray samples has been performed to quantify the number of cells per spot, the size of spots and the DNA amount per cell in each spot. The reproducibility of these parameters was found to be high. PMID- 17726267 TI - A golgi analysis of cortical pyramidal cells in the unilateral parkinson rat: absence of change in the affected hemisphere vs hypertrophy in the intact hemisphere. AB - PURPOSE: Unilateral dopamine (DA) depletion in the rat provides an analog of human Parkinson's disease. The classic view of DA loss is that it produces changes in the activity of striatal-cortical circuitry that results in reduced frontal cortex neural activity. This "functional deafferent" view is consistent with findings that animals display sensorimotor deficits in the contralateral-to lesion side of the body and compensatory behavior adjustments in the ipsilateral to-lesion side of the body. The present study examined how DA depletion and the associated sensorimotor changes affect the morphology of the ipsilateral or contralateral neocortex neurons as assessed by dendritic morphology in Golgi stained tissue. METHOD: Rats were given unilateral 6-hydroxydopamine (6-OHDA) or sham lesions in the nigrostriatal bundle. Lesion success was confirmed by enduring bilateral motor impairments in a skilled-reaching task, compensatory use of the ipsilateral-to-lesion limbs, and by increases in amphetamine and apomorphine-induced rotational behavior. RESULTS: Brains processed for Golgi-Cox staining at 1, 3, 8, or 24 months after the lesion showed no changes in dendritic arborization or synapse number in layer V pyramidal cells of motor cortex ipsilateral to the 6-OHDA lesion (DA-depleted hemisphere) at any postsurgical recovery stage. There was an increase in dendritic arborization in all lesion groups in the hemisphere contralateral to the lesion (good hemisphere). CONCLUSION: The results are inconsistent with the classical view of frontal cortex functional deafferentiation due to DA loss but do suggest that compensatory behavior leads to dendritic hypertrophy in the good hemisphere. PMID- 17726266 TI - The novel antiepileptic agent RWJ-333369-A, but not its analog RWJ-333369, reduces regional cerebral edema without affecting neurobehavioral outcome or cell death following experimental traumatic brain injury. AB - PURPOSE: To evaluate the therapeutic efficacy of two antiepileptic compounds, RWJ 333369 and RWJ-333369-A in a well-established experimental model of lateral fluid percussion (FP) traumatic brain injury (TBI) in the rat. METHODS: Anethestized Male Sprague-Dawley rats (n=227) were subjected to lateral FP brain injury or sham-injury. Animals were randomized to receive treatment with RWJ-333369 (60 mg/kg, p.o.) or its analog RWJ-333369-A (60 mg/kg, p.o.), or vehicle (equal volume) at 15 minutes, 4, 8, and 24 hours post-injury. In Study I, animals were assessed at 48 hours for acute motor and cognitive function and then sacrificed to evaluate regional cerebral edema. In Study II, animals were evaluated post injury for motor function at 48 hours and weekly thereafter from 1 to 4 weeks. Post-traumatic learning ability was assessed 4 weeks post-injury, followed by evaluation of hemispheric tissue loss. RESULTS: In Study I, no improvement in acute memory or motor function was observed following administration of either RWJ-333369 or RWJ-333369-A in brain-injured animals compared to vehicle-treated, brain-injured animals. However, brain-injured animals receiving treatment with RWJ-333369-A had a significant reduction in post-traumatic cerebral edema in both injured and contralateral hippocampus compared to brain-injured, vehicle-treated controls (p<0.05). In Study II, treatment with either compound did not result in any improvement of neuromotor function, learning ability or change in lesion volume following brain injury. CONCLUSION: These results indicate that the novel antiepileptic compound RWJ-333369-A reduces post-traumatic hippocampal edema without affecting neurobehavioral or histological outcome. It remains unclear whether this small effect on hippocampal edema ie related to the ability of this compound to attenuate seizure activity. PMID- 17726268 TI - Postural instability in patients with chronic stroke. AB - PURPOSE: It is known that visuospatial orientation and the extent of spontaneous recovery vary between right or left hemisphere affected stroke patients. We hypothesized that the right hemisphere affected chronic patients would show more impaired static balance than left hemisphere affected patients. The purpose of the study was to assess displacement of the center of pressure (COP) of ambulatory patients with either left or right hemiparesis. METHODS: Forty-five patients and thirty healthy subjects participated and static balance was measured while standing on a force plate. RESULTS: The patients showed more than four times higher mean velocity moment and two times faster anterior-posterior (AP) and medial-lateral (ML) speed of COP displacement than healthy subjects. The patients with left hemiparesis, and affected right hemisphere, had higher power peak magnitudes of COP displacements than patients with right hemiparesis both in ML and AP directions at low frequencies. The patients had higher power peak magnitudes of COP displacements than healthy subjects in both ML and AP directions at all separately analyzed frequency ranges. More weight bearing on the paretic side was associated with less COP displacement in ML and AP directions. CONCLUSIONS: Patients with left hemiparesis have more low frequency COP movements from side to side and from front to back than patients with right hemiparesis. Patients with right or left hemiparesis sway more than the healthy subjects. The affected hemisphere and the disturbed cerebral networks likely produce different postural deficits in right or left hemiparetic patients. PMID- 17726269 TI - Establishment of three-dimensional culture of neural stem/progenitor cells in collagen Type-1 Gel. AB - PURPOSE: Recent studies demonstrated that transplanting neural stem/precursor cells (NSPCs) into an injured spinal cord of adult rat promotes functional recovery. The functional recovery from spinal cord injury might be enhanced by transplanting NSPCs with a scaffold that fills the cavity, entraps the NSPCs in the cavity, and acts as an attachment for neurite extension. We recently focused on collagen type-1 as a scaffold for NSPC transplantation into the injured spinal cord. In the present study, we determined the optimal conditions for culturing NSPCs in 3D collagen type-1 gel with respect to cell survival and cell migration. We, then, evaluated the ability of NSPCs to differentiate under the optimal condition. METHODS: NSPCs were derived from the striatum of rat embryos. To determine the optimal cell density and collagen concentration for 3D collagen gel culture for NSPC, we performed viability assay and migration assay. Then, we examined the proportion of phenotypes differentiated from NSPC in that optimal condition. RESULTS: In viability assay, the viability rate increased as the NSPC density increased, and peaked at 1 x 10(7) to 5 x 10(7) cell/ml. For collagen concentration, the viability rate increased as the collagen concentration decreased. In migration assay, cell migration was most extensive at collagen concentrations between 0.3 and 0.75 mg/ml. Migration distances gradually declined as collagen concentrations increased. In the optimal condition, NSPCs differentiated into neurons (40.1%), astrocytes (53.1%), and oligodendrocytes (5.3%) in 3D collagen gel culture. CONCLUSION: The optimal conditions for NSPC culture in 3D collagen gel was a cell density between 1 x 10(7) and 5 x 10(7) cells/ml and a collagen concentration between 0.5 and 0.75 mg/ml. Under the condition, NSPCs could differentiate into neurons, astrocytes, and oligodendrocytes. PMID- 17726270 TI - Auditory temporal-order thresholds show no gender differences. AB - PURPOSE: Several studies on auditory temporal-order processing showed gender differences. Women needed longer inter-stimulus intervals than men when indicating the temporal order of two clicks presented to the left and right ear. In this study, we examined whether we could reproduce these results in order to further investigate the differences in auditory processing between men and women. METHODS: Neurologically healthy subjects (13 males and 13 females, age range: 19 to 37 years) had to identify the temporal order of two clicks, presented monaurally to the left and right ear. Thresholds for the inter-stimulus intervals between the clicks were determined using a three step transformed up-down procedure. RESULTS: The results show no influence of gender in the auditory temporal-order task. Inter-individual differences were, however, large, ranging from a threshold of around 15 ms to around 90 ms. CONCLUSION: Contrary to what was found in previous studies, no significant gender difference was measured in temporal-processing abilities using a task with monaurally presented clicks. PMID- 17726271 TI - Repeated sessions of noninvasive brain DC stimulation is associated with motor function improvement in stroke patients. AB - PURPOSE: Recent evidence has suggested that a simple technique of noninvasive brain stimulation - transcranial direct current stimulation (tDCS) - is associated with a significant motor function improvement in stroke patients. METHODS: We tested the motor performance improvement in stroke patients following 4 weekly sessions of sham, anodal- and cathodal tDCS (experiment 1) and the effects of 5 consecutive daily sessions of cathodal tDCS (experiment 2). A blinded rater evaluated motor function using the Jebsen-Taylor Hand Function Test. RESULTS: There was a significant main effect of stimulation condition (p=0.009) in experiment 1. Furthermore there was a significant motor function improvement after either cathodal tDCS of the unaffected hemisphere (p=0.016) or anodal tDCS of the affected hemisphere (p=0.046) when compared to sham tDCS. There was no cumulative effect associated with weekly sessions of tDCS, however consecutive daily sessions of tDCS (experiment 2) were associated with a significant effect on time (p< 0.0001) that lasted for 2 weeks after treatment. CONCLUSIONS: The findings of our study support previous research showing that tDCS is significantly associated with motor function improvement in stroke patients; and support that consecutive daily sessions of tDCS might increase its behavioral effects. Because the technique of tDCS is simple, safe and non expensive; our findings support further research on the use of this technique for the rehabilitation of patients with stroke. PMID- 17726272 TI - Long nerve gaps limit the regenerative potential of bioartificial nerve conduits filled with Schwann cells. AB - PURPOSE: Recently we successfully used a conduit of epsilon-caprolactone-co trimethylene carbonate filled with Schwann cells (SC) across a 20 mm gap in a rat median nerve. In this study we applied the tubes with SC across a 40 mm gap in order to analyse the regenerative potential of the tubes in long nerve defects. METHODS: To augment the nerve defect a cross-chest procedure was used and the tubes were implanted with injected isogeneic SCs inside (group 3). Both ulnar nerves were used for a 40 mm autograft (group 2). For control group non-operated animals were used (group 1). The grasping test, histology (S-100, PAM), electrophysiology, and the muscle weight were used to assess regeneration. RESULTS: After 12 months, grasping was seen only in three animals of group 3 (3.6 g [95% CI: 0 to 7.6 g]). However, in group 2 all rats had a partial functional regeneration (42.8 g [95% CI: 39.1 to 46.6 g]). The grasping force of the non operated animals (group 1) was 240.9 g [95% CI: 237.2 to 244.7 g] at the time. Histology from group 3 confirmed an irregular arrangement of fibres in contrast to more organized structures in group 2. Electrophysiology in group 3 displayed potentials only in the three animals with functional regeneration. In group 2 all animals exhibited potentials. A significant decrease of muscle weight was observed in groups 2 and 3, most prominent in the latter. CONCLUSION: Regeneration was not successful across the 40 mm gap using the applied tube in combination with SC. For future experiments further consideration should be taken in optimizing the cellular and material components that are critical for a successful application to overcome very large nerve gaps. PMID- 17726273 TI - No effect of a levodopa single dose on motor performance and motor excitability in chronic stroke. A double-blind placebo-controlled cross-over pilot study. AB - PURPOSE: Drugs that modulate neuronal transmission can influence motor recovery after stroke. Here, we tested if a single dose of levodopa could improve motor functions and change motor excitability in a group of chronic stroke patients. METHODS: Ten patients > 6 months after their stroke participated in a placebo controlled double-blind trial. On two different occasions, they received either 100 mg levodopa or placebo in a randomized order. After drug intake, they participated in one hour of physiotherapy aimed at an improvement of dexterity. Motor functions were tested by application of the Nine-Hole-Peg Test, a dynamometer measuring grip strength and the Action Research Arm Test. In addition, transcranial magnetic stimulation (TMS) was applied to study intracortical excitability, stimulus response curves and silent periods. TMS studies and motor function measurements were performed before drug intake, 45 minutes after drug ingestion and after the physiotherapy. RESULTS: Compared to placebo, levodopa neither improved motor functions nor changed motor excitability as tested by TMS. CONCLUSION: These findings suggests that a single levodopa dose is not sufficient to improve motor function in chronic stroke. However, it cannot be excluded that the lack of a beneficial effect is related to the small study sample. PMID- 17726274 TI - Progesterone inhibits ischemic brain injury in a rat model of permanent middle cerebral artery occlusion. AB - PURPOSE: Previous studies suggest that progesterone (PROG) has a substantial protective effect against several types of brain injury. Since most cases of human stroke are caused by permanent occlusion of cerebral arteries, we assessed the neuroprotective effects of PROG on cerebral infarction and behavioral deficits in a permanent MCAO (pMCAO) model. METHODS: pMCAO was produced by surgical insertion of a silicone-coated nylon filament into the right internal carotid artery. Laser-Doppler flowmetry was used to monitor cerebral blood flow for 10 min post-occlusion. PROG (8 mg/kg) or vehicle (2-hydroxypropyl-beta cyclodextrin) was administered intraperitoneally at 1 h post-occlusion followed by subcutaneous injections at 6, 24 and 48 h post-occlusion. Measurements of infarct volumes (cortical, subcortical and total) were performed at 72 h and functional recovery, assessed by rotarod test, were performed 24, 48, and 72 h after pMCAO. RESULTS: Following PROG treatment, stained sections revealed a significant reduction in cortical, caudate-putamen and hemispheric infarct volumes (% contralateral structure) compared to vehicle-injected controls. In addition, PROG treatment reduced functional deficits on the accelerating rotarod apparatus. CONCLUSION: We demonstrated and confirmed the neuroprotective effect of PROG using a permanent model of focal brain ischemia in rats. PMID- 17726275 TI - Heterotopic, not homotopic, fetal occipital allografts in adult hosts project to visual-related extracortical targets. AB - PURPOSE: Fetal occipital allografts implanted into the posterior cortex of adult mice project massively throughout the ipsilateral pallium of the host, but rarely outside this domain (Gaillard et al., 2004). The present study was undertaken to examine in detail whether this pattern is specific to graft location. METHODS: Cortical fragments corresponding to presumptive occipital areas were harvested from E15 mice fetuses expressing ubiquitously the eGFP protein, and implanted in correct (homotopic) and incorrect (heterotopic) cortical loci in wild-type adults. Two months later, efferents were detected by immunohistochemistry and quantified on selected DAB-treated sections. RESULTS: The present findings show (i) that robust projections are present in the ipsilateral host cortex regardless of the graft location; (ii) that 55% the grafts located in parietal and frontal cortices have obvious but sparse callosal and subcortical projections; and (iii) that grafts placed in occipital areas never contact ipsilateral subcortical targets, likely because graft-related axons are unable to cross obliquely the thalamocortical fascicles in the underlying white matter. CONCLUSIONS: These puzzling results question the use of transplantation strategies for repairing damaged networks in adults where rewiring involves complex white matter trajectories. PMID- 17726276 TI - Treatment of adult neural progenitor cells prior to transplantation affects graft survival and integration in a neonatal and adult rat model of selective retinal ganglion cell depletion. AB - PURPOSE: We tested whether microenvironmental changes surrounding apoptotic neural degeneration, cellular pre-treatment and timing of transplant can influence the survival and differentiation of transplanted cells. This was done by transplanting adult hippocampal precursor cells (AHPCs) into normal and retinal ganglion cell (RGC) depleted rat retinae. METHODS: Apoptotic RGC death was induced in neonates by removal of the contralateral superior colliculus (SC) and in adults by unilateral optic nerve transection, with or without a peripheral nerve (PN) graft. AHPCs were transplanted 24 h after SC ablation, or 5, 7 or 14 days following optic nerve (ON) transection. Hosts received untreated grafts, or grafts treated by co-culture with embryonic retinal explants or the neuropeptide somatostatin. RESULTS: AHPCs integrated within all neonatal and 65% of adult retinae. Greater numbers of AHPCs were observed within the ganglion cell layer (GCL) in SC lesioned hosts. Explant co-culture induced proliferation of grafted AHPCs within host retinae. Somatostatin-treatment resulted in reduced overall engraftment but increased integration within the GCL. In lesioned adults, greatest GCL engraftment was observed following 7 or 14 day grafts. Some AHPCs in the inner retina expressed neuronal antigens and extended processes into the ON. CONCLUSIONS: These data indicate that various factors can influence the behaviour of grafted cells and work towards encouraging the functional restoration of retinal circuitry. PMID- 17726277 TI - Anterior canal neurons in cat vestibular nuclei have large phase leads during low frequency vertical axis pitch. AB - Vestibulo-ocular and second-order neurons in medial and superior vestibular nuclei of alert cats were identified by antidromic and orthodromic electrical stimulation, and their responses to whole body rotations were recorded in the dark. Neurons that had spatial sensitivity most closely aligned with the anterior canal (anterior canal neurons) were compared with neurons that had spatial sensitivity most closely aligned with the posterior canal (posterior canal neurons). Responses were recorded during low frequency earth-horizontal axis pitch rotations in the normal upright posture, and during earth-vertical axis pitch with the head and body lying on the left side. During upright pitch, response phases of anterior canal neurons slightly lagged those of posterior canal neurons or primary vestibular afferents, as previously reported. During on side pitch, anterior canal neurons showed far greater phase leads with respect to head velocity than posterior canal neurons, primary vestibular afferents, or previously reported vestibulo-ocular reflex eye movements. These results provide challenges for vestibulo-ocular reflex models to incorporate central mechanisms for phase leads among the inputs to anterior canal neurons and to explain how the anterior canal neuron signals reported here combine with other signals to produce observed vestibulo-ocular reflex behavior. PMID- 17726278 TI - A "wait and learn" strategy of postural control learning in children? AB - This study compares the children and adult response to a novel postural challenge. One group of children (n=13, age 7-9) and one adult reference group (n=12 age 15-32) were subjected to vibration induced body sway and posturography with both open and closed eyes for 5 consecutive days. There was a gradual decrease of induced body sway over time in both groups (p< 0.001) between the subsequent trials, but only in the adult group was there a reduction of induced body sway over time within each trial (p< 0.05). The children had on a considerably less level of induced body sway when they started the second trial than they finished the first (p< 0.01). There appears to be a different approach of adaptation to a new postural challenge between children and adults. PMID- 17726279 TI - Linear vection as a function of stimulus eccentricity, visual angle, and fixation. AB - The effects of stimulus eccentricity, visual angle, and fixation on linear vection (sensation of self-translation induced by large moving scenes) were examined in healthy young people. Three aspects of vection were measured: latency, total vection time, and strength. The results showed that when peripheral and central stimuli are equal in area, they induce similar vection, but only when they are presented with a fixation cross. When presented without a fixation cross, peripheral stimuli are more effective in inducing vection than central stimuli. In addition, central stimuli with a fixation cross elicited more vection than central stimuli without a fixation cross. Fixation had no influence on the vection induced by peripheral stimuli. These findings indicate that statements about the role of central and peripheral stimuli of equal area in inducing vection should be made only in conjunction with reports about whether these stimuli are presented with or without fixation. PMID- 17726280 TI - Vestibular evoked myogenic potential threshold and seasickness susceptibility. AB - Numerous attempts have been made to find physiological parameters that might predict susceptibility to seasickness. However, to date, no physiological index has been found that can serve as a diagnostic tool for individual susceptibility to motion sickness at the personnel selection stage. A number of studies have demonstrated that linear acceleration in the vertical plane is the most provocative stimulus of motion sickness. The main physiological sensory modality responsible for monitoring vertical acceleration is the saccule. Over the last decade, vestibular evoked myogenic potentials (VEMP) have come to be recognized as a reliable procedure for the evaluation of saccular function. We used the VEMP test to assess otolith responses in 15 seasickness-susceptible (SS) and 15 non seasickness-susceptible (NSS) healthy male crew members. The SS group exhibited a significantly higher VEMP threshold and a significantly lower peak-to-peak p13 n23 amplitude interval compared with the NSS group. Further analysis by logistic regression found threshold to be the dominant factor associated with seasickness susceptibility. The study demonstrated differences in the VEMP reflex of the SS and NSS groups. The threshold difference may represent an intrinsic mechanistic difference between the vestibular systems of the two groups. Theoretically, increased susceptibility to seasickness may be due to a discrepancy between the various neural systems as a result of reduced otolith responses. PMID- 17726281 TI - Effects of fast head turns on head, trunk and pelvis motions during standing and walking in patients with unilateral vestibular deficit. AB - Patients with unilateral vestibular deficit (UVD) report difficulties with maintaining balance while executing fast head turns. Our aim was to determine whether head, trunk, and pelvis angular displacements were symmetrical in patients with UVD as they executed voluntary yaw rotation of the head towards or away from the side of the vestibular lesion, during standing and walking. Eight patients who underwent surgical resection of an acoustic neuroma stood with feet together or walked at comfortable pace across a 10-meter walkway. They turned the head as quickly and as fast as possible in the direction indicated by an illuminating arrow (left, right or none). The head angular displacement was similar towards the affected and intact sides. Acceleration tended to be larger during head rotations towards the affected versus the intact side by 13% at the head, 42% at the trunk and 37% at the pelvis (p> 0.05, NS). The pelvis rotated opposite to the head in 65% of trials towards the affected side and 56% of the trials towards the intact side during standing and 81% and 69%, respectively during walking. Overall, the UVD had only a minor influence on the symmetry of head, trunk and pelvis kinematics during fast yaw rotation of the head executed during standing and walking. PMID- 17726282 TI - Modification of compensatory saccades after aVOR gain recovery. AB - The recruitment of extra-vestibular mechanisms to assist a deficient angular vestibulo-ocular reflex (aVOR) during ipsilesional head rotations is well established and includes saccades of reduced latency that occur in the direction of the lesioned aVOR, termed compensatory saccades (CS). Less well known is the functional relevance of these unique saccades. Here we report a 42 y.o. male diagnosed with right unilateral vestibular hypofunction due to vestibular neuronitis who underwent a vestibular rehabilitation program including gaze stabilization exercises. After three weeks, he had a significant improvement in his ability to see clearly during head rotation. Our data show a reduction in the recruitment and magnitude of CS as well as improved peripheral aVOR gain (eye velocity/head velocity) and retinal eye velocity. Our data suggest an inverse, dynamic relationship between the recruitment of CS and the gain of the aVOR. PMID- 17726283 TI - Assessment of long-term work attendance within human service organisations. AB - Terms and theories of work attendance vary according to their use and focus. This paper analyzes long-term work attendance in relation to social, psychosocial, and health-related factors. Register-based and questionnaire-based data covering 3,804 human service organisation workers over a three-year period were analyzed at individual and work-unit level. The results showed positive relationships between work attendance and male gender, high income, work commitment, job satisfaction, and having positive feelings towards work. High work attendance combined with work commitment, stress, or pain did not show any negative long term effects upon short-term or long-term sick leave. Instead, work attendance seemed to be more associated with stable patterns of behaviour. Register-based measures of work attendance (at most 4-7 days of sick leave per worker per year) may be a useful tool in managing psychosocial work environment and related behaviour, but their inability to encompass information regarding individual health and disease must be borne in mind. PMID- 17726284 TI - Health professionals' attitudes and practices in relation to Functional Capacity Evaluations. AB - Functional Capacity Evaluations (FCE's) are part of practice in work injury prevention and rehabilitation, and are designed to define an individual's functional abilities or limitations in the context of safe, productive work tasks. Qualitative research methodology was used to investigate the attitudes and behaviours of health professionals in relation to FCE use. The study aimed to identify why health professionals chose a particular FCE, and to identify what factors influence health professionals' clinical judgements when providing results and recommendations for the individual being assessed. Five health professionals from the Hunter Region of New South Wales, Australia, participated in semi-structured, individual interviews using a phenomenological approach. Following inductive analysis of the data, four themes reflecting participants' attitudes and behaviours of FCE use emerged: i) referrals and expectations, including why and when the assessment is completed ii) outcomes, -- what the results aim to provide iii) workplace/practice/usage issues and iv) skills of the assessor. The results indicate the need for further research on the clinical utility of FCE's. A large scale quantitative study would allow results to be generalised to a wider community of FCE users. PMID- 17726285 TI - Occupational musculoskeletal injuries in the health care environment and its impact on occupational therapy practitioners: a systematic review. AB - The purpose of this systematic review was to explore the occupational and personal factors associated with occupational musculoskeletal injuries among health care providers and to identify the psychosocial issues as a result of the injuries. Then, an extrapolation developed to link the potential risks to occupational therapy practitioners. The inclusion criteria that developed from ten articles was based on content from the health and social science literatures. Searches were conducted via internet databases, hard-copy search of bibliographies, and citation review of article references. This review included 22 research studies over the past fifteen years (1990-2005). Classic scientific research studies and classical readings that went beyond the specified period were also included. The review revealed that patient handling was the most common occupational factor to cause work-related injuries. Inexperience and young age were major personal factors associated with injuries. Fear, anger, isolation, inability to perform duties and leisure activities were common psychosocial issues as a result of the injuries. It was extrapolated that occupational therapy practitioners were at risk for occupational musculoskeletal injuries. Future studies are recommended to examine the prevalence and risk factors specific to occupational therapy practitioners. PMID- 17726286 TI - The views of sick-listed employees' immediate superiors on co-operation in vocational rehabilitation. AB - PURPOSE: The purpose of this research was to investigate the views of sick-listed employees' immediate superiors on co-operation in vocational rehabilitation before and during a systematic, multi-professional, client-centred, solution oriented co-operation project in vocational rehabilitation (SMVR intervention). METHOD: A same-subject study with a questionnaire was used, with 95 immediate superiors giving their views on co-operation both before and during the SMVR intervention. RESULTS AND CONCLUSIONS: The immediate superiors felt that the SMVR intervention was successful in promoting co-operation, and reported a significant decrease in referrals of employees from one organisation to another without the problem being resolved. Hence SMVR co-operation was experienced positively by the immediate superiors and in fact led to a joint responsibility in finding solutions. The immediate superiors saw greater possibilities than before for employees to resume regular or other jobs during the SMVR intervention. A more elaborate co-operation model such as the SMVR intervention increased the immediate superiors' experience of successful vocational rehabilitation. Organizations seeking to increase efficiency in vocational rehabilitation might well analyse their work methods and improve their forms of co-operation. PMID- 17726287 TI - After fifteen years: the response of small businesses to the Americans with Disabilities Act. AB - This study reports findings from field research on the perceptions of small business owners and managers of the impact of the Americans with Disabilities Act (ADA) on their firms. Binary Logistic Regression analyses indicate that the majority of owners have positive attitudes toward the act and exhibit high levels of compliance. Firm support for the ADA and participation in carrying out its requirements is driven by both positive and negative factors and extends well beyond the group of businesses that under the law are required to comply with Titles I and III of the legislation. The results suggest strongly positive impacts of the ADA in the areas of accommodating customers with disabilities and disabled employees who are already on the job. Specific factors influencing compliance decisions and accommodations spending are incorporated in a proposed model of firm behavior. PMID- 17726288 TI - Employment status of women with disabilities from the Behavioral Risk Factor Surveillance Survey (1995-2002). AB - Among working aged adults (18-64) with disabilities, three out of 10 (32%) work full or part-time, compared to eight out of 10 (81%) of those without disabilities [9]. In addition, 24.7% of women with a severe disability and 27.8% of men with a severe disability are employed, while women with a non-severe disability have an employment rate of 68.4% and men with a non-severe disability have an employment rate of 85.1% [14]. This study examined data from the Behavioral Risk Factor Surveillance Survey from 1995-2002 to determine whether or not disparities exist in the rate of unemployment for women with disabilities, compared to men with disabilities and women and men without disabilities. In addition, regression analysis looked at the how disability and gender predict the outcome of unemployment. Results showed that there has been essentially no change with regard to employment for any of these populations. In addition, disability and gender were found to be the strongest predictors of unemployment for women with disabilities. Possible explanations were discussed as to the reasons for the results and issues were presented for future research. PMID- 17726289 TI - Evidence-based practice in occupational health: description and application of an implementation effectiveness model. AB - Work-related muscuoloskeletal disorders (WMSDs) continue to represent the most costly category of occupational diseases. There is a growing body of literature regarding the causal nature of these injuries and effective intervention strategies. In this context, the consistent utilization of evidence-based practice (EBP) to address these problems can be viewed as one indicator of occupational health effectiveness. However, the routine integration of EBP remains elusive in occupational and physical therapy practice, including the occupational health arena. This article describes an implementation effectiveness model from the field of organizational management and applies it to the implementation of EBP within the occupational health practice arena. As a predictive or evaluative tool regarding implementation success, the model can assist clinic managers and clinicians in developing targeted approaches to EBP initiatives within any health care facility. PMID- 17726290 TI - Employment after spinal cord injury: the impact of government policies in Canada. AB - The British Columbia Paraplegic Association (BCPA) sought a research partnership to evaluate where its activities should be focused. A survey of members with disabilities of the BCPA included questions on employment and identified three priorities related to employment. These were the need for assistance in finding appropriate work, the impact of policies of government and insurance agencies, and attitudes of employers. This paper examines the social and political environment related to employment following spinal cord injury in British Columbia, Canada. There is no coherent set of goals underlying government employment and income programs in Canada. Incremental development of particular employment and income programs during the 20th century led to a patchwork of policies and programs, which deal with people differently according to the cause of their disability. Federal and provincial governments have attempted to educate employers and reduce barriers to employment of those with disabilities by focusing on anti-discrimination legislation and individual rights (e.g. the Employment Equity Act and the Canadian Human Rights Act). However, people with disabilities face non-accommodating environments, inadequate income support, lack of opportunities and little political influence which stem from an unfair distribution of societal resources, not from discrimination. Joint efforts of the BCPA and other disability organizations are likely to have the most impact on legislative changes. PMID- 17726291 TI - Unexpected barriers in return to work: lessons learned from injured worker peer support groups. AB - Some workers who are injured at work have unexpectedly prolonged absences from work. Experiences of workers who constitute a disproportionate cost to the return to-work system and the systemic and compliance-related barriers they encounter during the process of returning to work are reported. A qualitative interview based study was conducted with 37 members of three injured worker peer support groups in a Canadian province. Four dimensions of peer support were identified: worker experience of being misunderstood by system providers, need for advocates, social support, help with procedural complexities of the workers' compensation, and health care systems. Peer support constitutes a partial return-to-work solution for workers with injuries, but injured workers encounter an uneven playing field. Injured worker peer support group needs and activities show us that sensitivity to structural and social issues may lead to better return-to work outcomes. PMID- 17726292 TI - Further validation of Hanson's Learning Profile Indicator and Silver, Hanson, and Strong's Teaching Style Inventory. AB - The purpose of this study was to validate Hanson's Learning Profile Inventory (LPI) and Teaching Style Inventory (TSI) further, and to assess the degree to which self-reported style preferences on these scales corresponded to actual observable learning and teaching style behaviors of students and teachers in differing instructional situations. No significant differences were found between the reported and observed learning and teaching style preferences of students and their instructors. Further, student and teacher classifications on the GEFT test of field independence/dependence corresponded to their classifications on the introversion/extroversion scale of the LPI and TSI further clarifying and validating this component of this scale on these two measures. This study was a formative study with a small sample (N=12) due to the burdens of observational ratings, which needs to be replicated with a confirmatory study. PMID- 17726294 TI - Endothelial lipase is increased by inflammation and promotes LDL uptake in macrophages. AB - AIM: Endothelial lipase (EL) is a member of the lipoprotein lipase family that regulates HDL metabolism. EL is known to act as a bridging molecule for monocytes or lipoproteins in vascular endothelial cells. We investigated the role and regulatory mechanisms of EL expression in macrophages. METHODS: Macrophages originating from wild-type (EL+/+) and EL-deficient (EL-/-) mice were stimulated with lipopolysaccharide (LPS). The expression of EL mRNA was evaluated by northern blotting. DiI-LDL was used to measure the uptake of native low-density lipoprotein (nLDL). RESULTS: LPS increased EL mRNA levels by increasing intracellular oxidative stress in the macrophages. LPS did not affect EL expression in macrophages derived from Toll-like receptor 4 (TLR4) gene mutant mice, C3H/HeJ. The uptake of nLDL after LPS-treatment was significantly lower in macrophages from EL-/- mice than those from EL+/+ mice. Simvastatin suppressed the LPS-induced upregulation of EL expression and uptake of nLDL. CONCLUSIONS: EL expression is upregulated by LPS via TLR4 and promotes the uptake of nLDL by macrophages. Simvastatin inhibits the LPS-induced up-regulation and uptake in macrophages. Thus, our findings provide a novel role for EL in lipoprotein metabolism and would expand the range of anti-atherogenic effects of statins. PMID- 17726293 TI - Hepatocyte growth factor fusion protein having collagen-binding activity (CBD HGF) accelerates re-endothelialization and intimal hyperplasia in balloon-injured rat carotid artery. AB - AIM: Hepatocyte growth factor (HGF) is known to stimulate endothelial cell proliferation. However, re-endothelialization is not enhanced when the native protein is administered to the injured artery, probably due to the short half life of HGF at the site of injury. Therefore, the effects of an HGF fusion protein having collagen-binding activity (CBD-HGF) on re-endothelialization and neointimal formation was studied in the balloon-injured rat carotid artery. METHODS: The left common carotid artery of male Sprague-Dawley rats was injured with an inflated balloon catheter, and then treated with CBD-HGF 10 microg/mL), HGF (10 micro g/mL) or saline (control) for 15 min. After 14 days, the rats were injected with Evans blue and sacrificed. RESULTS: The re-endothelialized area was significantly greater in the CBD-HGF- treated rats than in the control or HGF treated rats. Neointimal formation was significantly more pronounced in the CBD HGF treated rats than in other rat groups. Both HGF and CBD-HGF stimulated proliferation of vascular smooth muscle cells as well as endothelial cells in vitro. Consistent with this, cultured smooth muscle cells were shown to express the HGF receptor (c-Met). CONCLUSION: CBD-HGF accelerates re-endothelialization and neointimal formation in vivo. CBD fusion protein is a useful vehicle to deliver vascular growth factors to injured arteries. PMID- 17726295 TI - Aspirin for primary prevention of atherosclerotic disease in Japan. AB - Atherosclerotic disease is the most prevalent cause of death worldwide. The ratio of coronary heart disease/cerebrovascular disease differs between Japan and Western countries and the incidence of hemorrhagic stroke and gastrointestinal bleeding is higher in Japan. Thus, the threshold for aspirin administration for primary prevention has been controversial in Japan. Much anecdotal data from Western countries and from Japan has implied that the threshold for administering aspirin to those with risk factors for coronary heart disease is higher than that recommended in Western countries, and that the potential candidates for primary prevention in Japan seem to be diabetic patients. The Japanese primary Prevention of atherosclerosis with Aspirin for Diabetes (JPAD) trial involving 2,530 patients with type 2 diabetes started in December 2002. Compared to other primary prevention trials, this trial offered an acceptable sample size, a standard aspirin dosage, and gender balance. Because stroke is the most significant component of all atherosclerotic diseases in Japan, the impact of primary prevention with aspirin on stroke should be understood. Thus, the JPAD trial should generate reliable data on primary prevention with aspirin for diabetic patients that would also be relevant to other countries. PMID- 17726296 TI - Nonomuraea maheshkhaliensis sp. nov., a novel actinomycete isolated from mangrove rhizosphere mud. AB - A strain of Nonomuraea was isolated from Maheshkhali, Cox's Bazar, an unexplored region of Bangladesh. Strain 16-5-14(T) is a Gram-positive, aerobic, non-motile actinomycete that formed branched substrate and aerial mycelia. On the basis of 16S rRNA gene sequence similarity studies, strain 16-5-14(T) was shown to belong to the genus Nonomuraea, being most closely related to Nonomuraea kuesteri. Chemotaxonomic data supported allocation of the strain as a member of the genus Nonomuraea. The strain 16-5-14(T) contained MK-9(H(4)) as the major menaquinone, the polar lipid was phosphatidylethanolamine and major cellular fatty acids were observed as C(16 : 0 )(15.5%), iso-C(16 : 0) (13.8%) and 10-methyl C(17 : 0) (9.6%). Results of DNA-DNA hybridization and physiological tests allowed genotypic and phenotypic differentiation of strain 16-5-14(T) from closely related species N. kuesteri. Thus 16-5-14(T) represents a novel species of the genus Nonomuraea. On the basis of evaluation of the morphological, physiological and chemotaxonomic characteristics, 16S rRNA gene sequence comparisons and DNA DNA hybridization, Nonomuraea maheshkhaliensis sp. nov. (type strain, 16-5 14(T)=JCM 13929(T)=MTCC 8545(T)) is proposed. PMID- 17726297 TI - Asterotremella gen. nov. albida, an anamorphic tremelloid yeast isolated from the agarics Asterophora lycoperdoides and Asterophora parasitica. AB - Using a genotypic approach (PCR-fingerprinting, DNA/DNA reassociation, partial sequences of the 26S rDNA gene, complete sequences of the 18S rDNA gene, and sequences of the internal transcribed spacers) five tremelloid yeast isolates from the agarics Asterophora lycoperdoides and A. parasitica were shown to be conspecific with Cryptococcus ramirezgomezianus. It was not possible to distinguish the yeast strains from A. lycoperdoides and A. parasitica using sequences from the intergenic spacer (IGS1). Phylogeny based on the 26S (D1/D2 domain), ITS1-5.8S-ITS2 and complete 18S rDNA demonstrated that C. ramirezgomezianus is closely related to several additional Cryptococcus species (C. humicola, C. longus, C. musci, C. pseudolongus) within the Trichosporonales. A new genus, Asterotremella, and a new family, Asterotremellaceae were introduced for Cryptococcus species clustering within the Trichosporonales having a ubiquinone Q-9. Cryptococcus ramirezgomezianus is a synonym of Asterotremella albida. PMID- 17726298 TI - Characterization of alcohol oxidase from Aspergillus ochraceus AIU 031. AB - An alcohol oxidase (AOD) was found from Aspergillus ochraceus AIU 031, and its characteristics were revealed. This enzyme oxidized short-chain primary alcohols and ethylene glycol, and belonged to the same group as AOD from methylotrophic yeast. However, it differed in the following properties. The K(m) value for ethanol was larger and that for ethylene glycol was smaller than those of AODs derived from methylotrophic yeasts. The ethanol oxidation was optimal at pH 5-7 and 50-55 degrees C. The molecular mass of this enzyme was 262 kDa and consisted of four identical subunits of 68 kDa, which were much smaller than those of methylotrophic yeasts. PMID- 17726299 TI - Janibacter corallicola sp. nov., isolated from coral in Palau. AB - A novel Janibacter species is described on the basis of phenotypic, chemotaxonomic and genotypic data. Two bacterial strains were isolated in Palau, which were both Gram-positive, catalase-positive bacteria with meso diaminopimelic acid as the diagnostic diamino acid of the peptidoglycan. The major menaquinone was MK-8(H(4)). Mycolic acids were not detected. The G+C content of the DNA was 70-71 mol%. Comparative 16S rDNA studies of the two isolated strains revealed that they both belonged to the genus Janibacter. DNA DNA relatedness data revealed that 04PA2-Co5-61(T) and 02PA-Ca-009 belong to the same species, a new species of the genus Janibacter. From these results, Janibacter corallicola sp. nov. is proposed, with the type strain 04PA2-Co5-61(T) (=MBIC 08265(T), DSM 18906(T)). PMID- 17726300 TI - Molecular profiling of Lactobacillus, Streptococcus, and Bifidobacterium species in feces of active racehorses. AB - Diversity and compositions of the Lactobacillus, Streptococcus, and Bifidobacterium group in the feces of six healthy, actively racing horses (Thoroughbreds) were analyzed by using PCR-denaturing gradient gel electrophoresis (DGGE) and real-time PCR with primer sets specific for each group. PCR-DGGE analysis of the feces showed that Lactobacillus equi, Lactobacillus johnsonii, a phylogenetic relative of Lactobacillus salivarius, a phylogenetic relative of Lactobacillus gastricus, and Weissella confusa were predominant in almost all of the feces tested, and Streptococcus bovis/Streptococcus equinus was predominant in the Streptococcus group. The Bifidobacterium group was not detected by single-PCR but atypical species of the group were found in three of the six Thoroughbreds tested by nested-PCR. Calculation and estimation of lactic acid bacteria and bifidobacteria revealed that lactic acid bacteria were predominant in the feces and bifidobacteria were minor. These results indicate that the community of lactic acid bacteria and bifidobacteria in horse feces are unique because of the presence of specific species for horse feces and a minority of the Bifidobacterium group. Repeated tests of the feces from the same horse over 3 months showed that the diversity and composition of lactic acid bacteria and bifidobacteria in the feces was basically stable throughout the test period. PMID- 17726301 TI - Effect of herb lignin on the growth of enterobacteria. PMID- 17726302 TI - Screening of probiotic properties of lactic acid bacteria isolated from Kanjika, an ayruvedic lactic acid fermented product: an in-vitro evaluation. PMID- 17726303 TI - Enhancement of freezing-resistance of Lactobacillus rhamnosus by the application of cell immobilization. PMID- 17726304 TI - Ascorbic acid monoglucoside as antioxidant and radioprotector. AB - Ascorbic acid monoglucoside (AsAG), a glucoside derivative of ascorbic acid, has been examined for its antioxidant and radioprotective abilities. AsAG neutralized 1, 1 diphenyl -2-picryl-hydrazyl (DPPH), a stable free radical in a concentration dependent manner thus indicating its antioxidant ability. AsAG protected mice liver tissues in vitro from peroxidative damage in lipids (measured as TBARS) resulting from 25Gy gamma irradiation. It also protected plasmid pBR322 DNA from gamma-radiation induced strand breaks as evidenced from studies on agarose gel electrophoresis of the plasmid DNA after radiation exposure. Oral administration of AsAG to mice prior to whole body gamma radiation exposure (4Gy) resulted in a reduction of radiation induced lipid peroxides in the liver tissue indicating in vivo radiation protection of membranes. Pulse radiolysis studies indicated that AsAG offered radioprotection by scavenging free radicals. The rate constants for the reactions OH and N(3) radicals with AsAG were determined to be 6.4 x 10(9) dm(3) mol(-1) s(-1) and 2.3 x 10(9) dm(3) mol(-1) s(-1), respectively at pH 7. It was observed that AsAG radicals undergo conjugation as the pH of the solution is raised to 11 in the case of a one-electron oxidation reaction. As the OH(*) radical adds to the ring, the conjugation effect starts appearing at pH 10. PMID- 17726306 TI - Defective platelet aggregation in myelodysplastic syndromes. AB - INTRODUCTION: Hemorrhagic tendency in patients with myelodysplastic syndrome (MDS) is mainly attributed to thrombocytopenia. However, platelet function in these patients has not been thoroughly investigated. AIM: The aim of our study is to evaluate platelet function in patients with primary MDS. METHODS: Platelet function was studied with aggregometry in response to ristocetin, collagen, ADP and adrenaline in 26 MDS patients and 15 healthy individuals. RESULTS: Aggregation was defective in 21 patients (80.7%). Adrenaline was the agonist with the most profound defect (45.9%), followed by ADP (58.7%), whereas aggregation with ristocetin and collagen was at the borderline. Abnormal aggregation to all four agonists was detected in 6 patients (23%). On the contrary, aggregation results were normal in only 5 patients (19.2%). RAEB-t (refractory anemia with excess blasts in transformation) patients were most seriously affected. CONCLUSIONS: MDS patients have impaired platelet aggregation in response to one or more stimulants. Platelet aggregation was not statistically different between MDS patients at early stages of the disease (<12 months) and those at later stages (>12 months). Defective platelet aggregation is strongly related to MDS of worse prognosis. None of our patients was detected to have hyperfunctional platelets, defined as platelets aggregating spontaneously. Functional defects in MDS do not elicit hemorrhagic tendency. PMID- 17726305 TI - Implants of estradiol conjugated to bovine serum albumin in the male rat medial preoptic area promote copulatory behavior. AB - The expression of mating behavior in male rats is dependent on estrogen responsive neurons in the medial preoptic area (MPO). Previous reports showed that mating is attenuated if the aromatization of testosterone to estradiol (E2) is blocked in the MPO and that mating is maintained by MPO E2 implants. However, the mechanisms by which E2 exerts its action are not fully understood. It had been thought that E2 acted exclusively by binding to nuclear estrogen receptors to exert it effects; however, recent reports suggest that E2 also binds to membrane-associated receptors activating downstream intracellular cascade responses. In this study, we aimed to determine if an action of E2 at the cell surface is sufficient to support mating behavior. Therefore, either vehicle, E2, or E2 conjugated to bovine serum albumin (BSA-E2: a complex of E2 and a large protein that will not cross the plasma membrane, thereby restricting the action of E2 to cell surface signaling) was chronically administered bilaterally to the MPO of castrated, dihydrotestosterone-treated male rats. Mating behavior was supported by MPO BSA-E2 implants, suggesting that E2 operates in the MPO via a cell surface mechanism to facilitate male rat mating behavior. PMID- 17726307 TI - A novel mutation of COL4A3 presents a different contribution to Alport syndrome and thin basement membrane nephropathy. AB - BACKGROUND: Alport syndrome (AS) and thin basement membrane nephropathy (TBMN) are heterogeneous renal hereditary diseases. Mutations of COL4A3 and COL4A4 genes were reported to be the underlying pathogenicity in both diseases. However, the mechanism of the same mutation causing totally different clinical processes and outcomes in AS and TBMN is still not clear. SUBJECTS AND METHODS: Mutations of all coding exons of COL4A3 and COL4A4 were screened in a patient with autosomal recessive Alport syndrome (ARAS) of a Chinese Han consanguineous family by means of PCR and direct sequencing. Furthermore, the identified mutation was validated by restriction endonuclease AvaII in all 20 members in his family, as well as 46 patients with TBMN, 2 patients with AS from another two families, and 50 healthy controls. RESULTS: A novel missense mutation (3725G>A, G1242D) in exon 42 of COL4A3 was identified in the proband in the homozygous form. This pathogenic mutation was demonstrated in all carriers who presented with hematuria or mild proteinuria in the heterozygous form, whereas it was not detected in others whose urinalysis was normal within the family. In addition, 10 polymorphisms, including 1 non-glycine missense variant and 9 neutral polymorphisms, were detected in COL4A3/COL4A4. CONCLUSION: The novel mutation (3725G>A, G1242D) of COL4A3 was the underlying pathogenic role in the homozygous form in ARAS and in the heterozygous form in TBMN within an identical family. The result provided a potentially useful clue for the functional investigation of COL4A3 in these two hereditary glomerular disorders. PMID- 17726308 TI - Contribution of selected vitamins and trace elements to immune function. AB - Adequate intakes of vitamins and trace elements are required for the immune system to function efficiently. Micronutrient deficiency suppresses immune functions by affecting the innate T-cell-mediated immune response and adaptive antibody response, and leads to dysregulation of the balanced host response. This increases the susceptibility to infections, with increased morbidity and mortality. In turn, infections aggravate micronutrient deficiencies by reducing nutrient intake, increasing losses, and interfering with utilization by altering metabolic pathways. Insufficient intake of micronutrients occurs in people with eating disorders, in smokers (both active and passive), in individuals with chronic alcohol abuse, in patients with certain diseases, during pregnancy and lactation, and in the elderly. With aging a variety of changes are observed in the immune system, which translate into less effective innate and adaptive immune responses and increased susceptibility to infections. Antioxidant vitamins and trace elements (vitamins C, E, selenium, copper, and zinc) counteract potential damage caused by reactive oxygen species to cellular tissues and modulate immune cell function through regulation of redox-sensitive transcription factors and affect production of cytokines and prostaglandins. Adequate intake of vitamins B(6), folate, B(12), C, E, and of selenium, zinc, copper, and iron supports a Th1 cytokine-mediated immune response with sufficient production of proinflammatory cytokines, which maintains an effective immune response and avoids a shift to an anti-inflammatory Th2 cell-mediated immune response and an increased risk of extracellular infections. Supplementation with these micronutrients reverses the Th2 cell-mediated immune response to a proinflammatory Th1 cytokine-regulated response with enhanced innate immunity. Vitamins A and D play important roles in both cell-mediated and humoral antibody response and support a Th2-mediated anti inflammatory cytokine profile. Vitamin A deficiency impairs both innate immunity (mucosal epithelial regeneration) and adaptive immune response to infection resulting in an impaired ability to counteract extracellular pathogens. Vitamin D deficiency is correlated with a higher susceptibility to infections due to impaired localized innate immunity and defects in antigen-specific cellular immune response. Overall, inadequate intake and status of these vitamins and minerals may lead to suppressed immunity, which predisposes to infections and aggravates malnutrition. PMID- 17726309 TI - Diet quality of pregnant women attending an antenatal clinic in Nakuru, Kenya. AB - BACKGROUND/AIMS: To determine diet quality and common food sources of various nutrients of pregnant Kenyan women. METHODS: Cross-sectional study of 716 pregnant women attending the antenatal clinic at the Provincial General Hospital, Nakuru, Kenya. Nutrient intake was estimated using the 24-hour dietary recall method. RESULTS: Inadequate nutrient intake was found for energy, total folic acid, calcium, iron and zinc. Adequate intake was found for protein, fat, PUFA, carbohydrate, dietary fiber, vitamins A and C. Diet quality was poor as evidenced from the food sources of various nutrients. Maize flour was the most common source of the following nutrients: energy, protein, total folic acid, iron and zinc. Young women and those of low socio-economic status were at risk of inadequate intake of some of the nutrients. CONCLUSION: The results of this study indicate poor-quality diets of pregnant women attending the antenatal clinic, low in multiple micronutrients. Nutrient education for dietary diversification and nutrient supplementation should be explored as interventions for improving nutrient intake among pregnant women. PMID- 17726310 TI - A case of early diagnosed carnitine deficiency presenting with respiratory symptoms. AB - INTRODUCTION: Carnitine deficiency is an autosomal recessively inherited disease characterized by a low carnitine concentration in plasma and tissues. Primary carnitine deficiency (PCD) is caused by a deficiency in the plasma membrane carnitine transporter, with urinary carnitine wasting causing systemic carnitine depletion. The most common presentation of PCD is hypoketotic hypoglycemic encephalopathy. Cardiomyopathy can also be seen. CASE REPORT: A 9-month-old girl was admitted to our clinic with wheezing, respiratory distress and nighttime cough. She was pale, expirium was prolonged, breath sounds were coarse bilaterally and were increased in the right hemithorax. RESULTS: She had hypochromic microcytic anemia and the serum CPK level was elevated. Cardiothoracic index was increased (0.62). In the chest X-ray there was hyperaeration especially in the upper regions of the left lung, and paracardiac infiltration in the right lung. The echocardiogram showed dilated cardiomyopathy. In pulmonary perfusion scintigraphy, perfusion of the right lung was 26% and of the left lung 74%. Cardiomegaly and dilatation in main the pulmonary artery was detected in the MR angiogram. Plasma carnitine and acylcarnitine levels were found to be significantly low. Fat accumulation in myocytes and rare atrophic fibers were detected in a muscle biopsy. Oral carnitine supplementation was started at a dose of 100 mg/kg. All the symptoms and findings regressed within a short period of time. DISCUSSION: This case was presented to emphasize that carnitine deficiency can present with respiratory tract symptoms like wheezing and recurrent respiratory tract infections. Although PCD usually presents with hypoketotic hypoglycemia in infants, it also has to be suspected in the etiology of dilated cardiomyopathy. Treatment is very easy and lifesaving once the correct diagnosis is made, and the prognosis is excellent with lifelong carnitine supplementation. PMID- 17726311 TI - Overall glycemic index and glycemic load of vegan diets in relation to plasma lipoproteins and triacylglycerols. AB - BACKGROUND: To investigate the overall glycemic index (GI), glycemic load (GL), and intake of dietary fiber, and to examine the associations between these factors and plasma lipoproteins and triacylglycerols in adult vegans in the German Vegan Study (GVS). METHODS: Cross-sectional study, Germany. Healthy men (n = 67) and women (n = 87), who fulfilled the study criteria (vegan diet for >or=1 year prior to study start; minimum age of 18 years; no pregnancy/childbirth during the last 12 months) and who participated in all study segments. RESULTS: The average dietary GL of the GVS population was 144, and the average GI was 51.4. The adjusted geometric mean total, HDL, and LDL cholesterol concentrations decreased across the increasing quartiles of GL, carbohydrate and dietary fiber intake. The associations between total cholesterol, HDL cholesterol, LDL cholesterol and GL density and GI were inconsistent. Also, associations between GI, GL, the intake of carbohydrates, and triacylglycerol concentration were not observed. CONCLUSIONS: Fiber-rich vegan diets are characterized by a low GI and a low to moderate GL. The data do not support the hypothesis that a carbohydrate rich diet per se is associated with unfavorable effects on triaclyglycerols that would be predicted to increase the risk of coronary heart disease. PMID- 17726313 TI - Effects of various dietary amino acid preparations for phenylketonuric patients on the metabolic profiles along with postprandial insulin and ghrelin responses. AB - AIM: We investigated the metabolic profiles along with insulin and ghrelin responses following ingestion of various amino acid (AA) substitutes commonly used in the treatment of phenylketonuria to study the effects of added macronutrients. METHODS: Twenty healthy and 6 phenylketonuric adults ingested AA mixtures with or without carbohydrates and fat (Anamix, Easiphen, or p-am 3; 0.35 g AA/kg body weight); milk powder shakes were used for control purposes. Serum AA, glucose, urea, insulin, and ghrelin were measured over 5 h. RESULTS: Peak AA concentrations were achieved at around 60 min postprandially for supplemented AA powders and control shakes, significantly later than for pure AA. Of interest, the mean Phe/Tyr ratio declined by 40-50% in phenylketonuric patients following intake of Easiphen, Anamix, or p-am 3. The insulin peaks, up to 500% as compared with baseline, occurred at 30 min and were approximately 100% higher after intake of AA plus macronutrients. Glucose and urea remained constant. Ghrelin showed a nadir at 60 min, followed by a rise leading to a 30% increase of initial concentrations for pure AA as compared with more constant levels for preparations with macronutrients. CONCLUSION: An oral AA bolus together with macronutrients retards hyperaminoacidemia, displays a higher insulin secretion, normoglycemia, and more stable ghrelin concentrations, whereas the pure AA tested here exerted weaker anabolic effects. PMID- 17726312 TI - Effects of zinc on hepatic antioxidant systems and the mRNA expression levels assayed by cDNA microarrays in rats. AB - BACKGROUND: This study evaluated effects of zinc on the hepatic lipid peroxidation, antioxidant components and mRNA expression levels in rats. METHODS: Three diets with different Zn levels including Zn adequacy (ZA; 34.50 mg/kg, control), Zn deficiency (ZD; 3.30 mg/kg), and Zn overdose (ZO; 345.45 mg/kg) were fed to rats for 6 weeks. The mRNA expression levels were analyzed by cDNA microarrays. RESULTS: The body weight of rats fed the ZD diet was less (p < 0.01) than that of rats fed the ZA diet. Zn overdose elevated body weight, but the increase was not detected (p > 0.05) at week 6. Although copper and iron status in serum were declined (p < 0.01), those in liver were not affected (p > 0.05) by the high intake of zinc. The glutathione peroxidase (GPx) and glutathione (GSH) remained unchanged (p > 0.05) by zinc treatment. Rats fed the ZD diet showed reductions(p < 0.01) in the Cu-Zn superoxide dismutase (Cu-Zn SOD) and catalase (CAT) activity, and increases (p < 0.01) in the malondialdehyde and hydrogen peroxide (H(2)O(2)) contents. Rats fed the ZO diet particularly had higher Cu-Zn SOD (p < 0.01) activity. The mRNA expression levels of SOD were upregulated in the ZO group, and CAT was downregulated in the ZD group, while no changes in GPx mRNA levels were found after zinc treatment. CONCLUSION: The study suggested that zinc deficiency largely decreased body weight; zinc overdose, however, moderately stimulated growth in the early growing phase of rats. High dietary zinc did not compete with liver copper and iron status. Although Zn deficiency impaired antioxidant functions, zinc overdose hardly enhanced the antioxidant systems of animals. PMID- 17726314 TI - Changes in the immune system after moderate beer consumption. AB - BACKGROUND/AIM: Epidemiological studies have suggested that moderate alcohol consumption is associated with lower morbidity. However, intervention studies are needed to elucidate mechanisms involved. This study was aimed to determine the effects of moderate beer consumption on the immune function of healthy adults, taking into account gender differences. METHODS: After a 30-day alcohol abstinence period, 57 healthy volunteers consumed a moderate intake of beer (330 ml for women and 660 ml for men) for 30 days. Total leukocyte and lymphocyte counts; absolute values of T-lymphocyte CD3+, CD4+, and CD8+ subsets; delayed hypersensitivity skin response (DHSR); absolute values of B lymphocytes (CD19+) and serum immunoglobulin concentrations (IgG, IgA, and IgM); and cytokine production (IL-2, IL-4, IL-6, IL-10, IFN-gamma, and TNF-alpha) were evaluated following the abstinence and alcohol consumption periods. RESULTS: After moderate beer consumption CD3+ cells increased only in women (p < 0.05). IgG, IgM, and IgA concentrations, as well as IL-2, IL-4, IL-10, and IFN-gamma cytokine production increased while IFN-gamma/IL-10 ratio decreased in both men and women (p < 0.05). The rest of the immunological parameters analyzed remained unchanged. CONCLUSION: Moderate beer consumption produced an immunomodulatory effect in a healthy adult Spanish population; this effect appears to be more relevant in women than in men. PMID- 17726315 TI - Modification of iron status in young overweight/mildly obese women by two dietary interventions designed to achieve weight loss. AB - AIMS: To determine the modification of iron status in a group of overweight/mildly obese women following two different weight control programs. METHODS: The study subjects were 57 women who were assigned to one of two slightly hypocaloric diets: V (increased consumption of vegetables), or C (increased consumption of cereals, especially breakfast cereals). All data were determined at the start of the study and at 2 and 6 weeks into the dietary intervention period. RESULTS: Both diets led to a reduction in body weight and heme iron intake, and an increase in the intake of total and non-heme iron, at 2 and 6 weeks. At 6 weeks, a reduction in transferrin levels was seen in C subjects. Subjects with the worst initial iron status (hemoglobin 20 microM) increased Ca(i) in a concentration-dependent, ryanodine- and FK-506-sensitive way, with a potency significantly exceeding that of 20 mM caffeine. Moreover, the same active bastadins at a concentration of 5 muM in the presence of ryanodine prevented a thapsigargin-induced increase in Ca(i). These results indicate that bastadins, acting in a structure-dependent manner, modify the activity of RyR2 in primary neuronal culture and provide new information about structure-related pharmacological properties of bastadins. PMID- 17726342 TI - Brain MRI and neurological deficit measurements in focal stroke: rapid throughput validated with isradipine. AB - BACKGROUND/AIMS: Isradipine, a calcium channel blocker, provides consistent protection of the brain from injury and reduces neurological deficits produced by ischemic stroke in hypertensive rats. In these experiments, isradipine was utilized to cross-validate both the serial MRI measurement of brain infarctions with histology measurements and to validate a series of simple neurological deficit tests in order to establish a more rapid, higher throughput approach to screening compounds for utility in stroke. METHODS: Spontaneously hypertensive rats were treated with vehicle, or 2.5 or 5.0 mg/kg isradipine and middle cerebral artery occlusion. T(2)-weighted MRI image analysis was compared to standard triphenyltetrazolium chloride-stained histological image analysis of brain sections to quantify isradipine neuroprotection 1, 3, and 30 days after middle cerebral artery occlusion (MCAO; stroke). In addition, serial evaluation (i.e. 1, 2, 5, 12, 20 and 30 days after MCAO) of four simple neurobehavioral tests were completed for each animal. Tests included assessment of hindlimb and forelimb function, and balance beam and proprioception performance. RESULTS: At 1, 3 and 30 days there was a significant positive correlation of the percent hemispheric infarct for T(2)-weighted MRI and histology (p < 0.05). Practically identical isradipine dose-response neuroprotection curves were observed for both measurement procedures. Isradipine produced a dose-related reduction in all neurological deficits scored by the four neurological deficit tests (p < 0.05). In addition, a significant time-related recovery from neurological deficits in vehicle-treated rats was observed (p < 0.05). The four different neurological deficit tests did provide unique time-related profiles of neurological recovery. CONCLUSIONS: The present study validates the use of serial MRI in experimental stroke and establishes several simple neurological tests that can be used to measure neurological/behavioral deficits associated with brain injury and brain recovery of function over time. Under these conditions, T(2)-weighted MRI and neurological testing required only about 10 min each per animal, thus providing rapid data collection and analysis and requiring reduced scientific personnel. PMID- 17726343 TI - Inhibition of phosphodiesterase type 4 decreases stress-induced defecation in rats and mice. AB - BACKGROUND/AIMS: Phosphodiesterase type 4 (PDE4) has been previously shown to regulate colonic contractile activity in vitro. In this study, the effects of PDE4 inhibition were assessed in a model of stress-induced defecation previously demonstrated to be due to increased colonic transit/evacuation. METHODS: Rats were individually placed in a mild restraint cage and placed into a 12 degrees C environment (cold-restraint stress) for 60 min. Mice received restraint (only) stress at room temperature for 30 min. Loperamide (positive control compound) or two different PDE4 inhibitors (rolipram and roflumilast) were administered orally at several doses to the rodents 1 h before stress began. Vehicle alone was administered for comparison. The number of fecal pellets expelled during stress (fecal pellet output), total fecal pellet wet weight and total fecal water content were measured. RESULTS: Loperamide produced a dose-related decrease (ID(50)s in mg/kg) in fecal pellet output (rat = 7.4, mouse = 0.7) and significantly decreased fecal wet weight (72.9%) and decreased fecal percent water content (9.4%). The two PDE4 inhibitors produced a similar dose-related inhibition of fecal pellet output. Rolipram exhibited ID(50)s in rat and mouse of 14.1 and 27.1, respectively. Rolipram significantly decreased fecal wet weight (58.8%) but increased fecal percent water content (15.0%). For roflumilast, ID(50)s were 24.2 mg/kg and 12.4 in the rat and mouse, respectively. Although roflumilast also significantly (p < 0.05) decreased fecal wet weight (47.2%), it did not significantly increase fecal percent water content. CONCLUSIONS: These data indicate that PDE4 inhibition is effective in reducing rodent stress-induced defecation, provides the first functional data on a potential role for PDE4 activity in the colonic evacuation response to stress, and indicates the potential utility of PDE4 inhibitors in functional bowel disease such as irritable bowel syndrome requires further evaluation. PMID- 17726344 TI - The effect of delta 9-tetrahydrocannabinol on the extinction of an adverse associative memory. AB - The cannabinoid Delta(9)-tetrahydrocannabinol (Delta(9)-THC) is currently being employed or tested for a number of therapeutic uses. Cannabinoid CB1 receptors are critically involved in adverse memory extinction. It is not known whether an unintended effect of Delta(9)-THC is increased extinction rates of adverse memories. We therefore tested the effect of Delta(9)-THC on adverse memory extinction using an auditory-stimulus/foot shock paradigm. We found that repeated administration of a high dose of Delta(9)-THC over 6 days retarded extinction compared with controls. This is in contrast to other reports and might be a result of endocannabinoid signalling dysfunction due to cannabinoid receptor densensitization. PMID- 17726345 TI - Epidemiology and risk factors in urolithiasis. AB - Stone formation in the urinary tract affects about 5-10% of the population in industrialized countries, although it is very rare in other countries such as Greenland or Japan. The high incidence and recurrence rate contribute to making the urolithiasis a serious social problem. Nowadays, urolithiasis must be considered a 'disease in evolution' for several reasons, such as epidemiological changes, evolution of the methods used for diagnosis, and the treatment and prophylaxis of the population considered 'at risk' of stone disease. Some features of stone disease have changed over the last few years due to many social, economical and cultural factors that are described here. The increased prevalence of small urinary calculi has brought about a change in clinical symptoms, with frequent episodes of renal-ureteral colic, persistent pain and hydronephrosis. Similarly, the presence of residual fragments after extracorporeal shock wave lithotripsy has induced a radical change in the management of small calculi through the use of mini-invasive surgical techniques. PMID- 17726346 TI - Lithiasis and risk factors. AB - Nephrolithiasis is a worldwide disease with high clinical and economic costs. The increasing incidence in industrialized countries seems to be related to several risk factors, which are partly inherited and partly acquired. Although risk factors in urolithiasis are still under discussion, their identification would provide a notable gain for the patient in terms of stone episodes, and for the health service in terms of costs. This article presents an easy classification of risk factors based on clinical background. PMID- 17726347 TI - Stone composition: where do we stand? AB - Kidney stones are a common disorder of the urinary tract. Nephrolithiasis is a morbid and expensive disease. The prevalence and incidence are estimated at 5-10% and 100-300/100,000/year, respectively. Relapses occur in 50-70% of all cases. For these reasons, prevention of stone formation is of great importance. Knowing the composition of the calculus is thus fundamental for a more complete evaluation of the metabolic study. The nature of the calculus in fact helps the physician to find a convenient metaphylaxis consisting of both sanitary and therapeutic measures. Study of the composition of urinary stones remains one of the most interesting aspects of the lithiasic pathology today. Presently crystallographic examination constitutes one of the most precise and less expensive methodologies to identify the nature of the concretion. This method also allows the urologist to catalogue the typology of the lithiasis during endoscopy. PMID- 17726348 TI - Laboratory assessment. AB - Nephrolithiasis has a multifactorial origin, and several disorders may coexist in the same patient. We made a basic and a specific laboratory evaluation. The complete metabolic evaluation consisted of a serum chemistry panel: blood sugar level, complete hemogram, serum electrolytes, GOT, GPT, calcium, phosphate, uric acid, and creatinine levels and RIA dosage of PTH, vitamin D3, cAMP, FT4, FT3 and TSH. The complete analyses of random urinalysis and culture are: (1) dip-stick test: pH, leukocytes/bacteria and Brand's test, and (2) 24-hour urine collection: calcium, magnesium, oxalate, phosphate, citrate, urea, urate, sodium, creatinine, chloride, potassium. It is possible with these tests to identify secondary causes of nephrolithiasis and uncover coexisting problems that may have an impact on patient management. The future for diagnosis, prevention and therapy will be the identification of genetic alterations and related specific dosage. PMID- 17726350 TI - Stones and urinary tract infections. AB - The term infection stones refers to calculi that occur following urinary tract infections (UTIs) caused by urease-producing gram-negative organisms. They consist of magnesium ammonium phosphate, carbonate apatite and monoammonium urate. Alkaline urine is most favorable to their formation. Urinary tract obstruction, neurogenic bladder, voiding dysfunction, temporary or indwelling urinary catheters, distal renal tubular acidosis and medullary sponge kidney are considered the main risk factors for developing infection stones. Urinalysis and urine culture are essential for diagnosis. A typical finding on imaging is a moderately radiopaque, staghorn or branched stone. Curative treatment is possible only by eliminating all of the stone fragments and by eradicating UTI. A variety of operative and pharmaceutical approaches is available. Metaphylactic treatment is mandatory to prevent recurrences. The relationship between urinary stones and UTIs is well known and shows two different clinical pictures: (1) stones that develop following UTIs (infection stones) which play a key role in stone pathogenesis, and (2) stones complicated by UTIs (stones with infection) which are metabolic stones that passively trap bacteria from coexistent UTIs and may consist of calcium or non-calcium. This article presents an overview of infection stones, analyzing the epidemiology, composition, pathogenesis, diagnosis, treatment and prevention of this type of calculi. PMID- 17726349 TI - Pathophysiology and clinical aspects of urinary lithiasis. AB - Urine is a complex balanced solution containing dissociated and non-dissociated solutes. Any variation in urine saturation grade (number of crystals dissolved in a volume of urine), urinary pH and the concentration of crystallization inhibitors can break the normal existing balance and lead to urolithiasis. In the present article we analyze the principal mechanisms (absorptive, renal, resorptive) of hypercalciuria. It will be also shown how heredity directly influences the clinical aspects of cystine, xanthine and oxalate lithiasis and how diet, in association with metabolic disorders, interferes in uric acid and oxalate stone formation. Finally, we report on the roles of urinary tract malformations, urinary tract infections and drugs in the clinical characterization of urolithiasis. PMID- 17726351 TI - Prevention of stone disease. AB - In recent years stone disease has become more widespread in developed countries. At present the prevalence is 5.2 and 15% of men and 6% of women are affected. The increase is linked to changes in lifestyle, eating patterns and obesity which has become very common. The 'metabolic syndrome' includes all the diseases, e.g. hypertension, lipid imbalances, type 2 diabetes mellitus, gout and cardiovascular disease, which are concomitant in the majority of stone formers. Dietary patterns, besides leading to stone formation, also determine stone chemistry. With a diet that is rich in oxalates, calcium oxalate will constitute 75% of stones, struvite 10-20%, uric acid 5-6% and cystine 1%. As approximately 50% of patients with stones suffer recurrences, metabolic and/or pharmacological prophylaxis is recommended. PMID- 17726352 TI - ESWL prediction of outcome and failure prevention. AB - Based on our own experiences and a review of the recent literature, this article evaluates recent developments in predicting outcomes and failures of shockwave lithotripsy when treating patients with urinary tract stones. After a detailed MEDLINE research, the authors identified several variables that influence and predict extracorporeal shockwave lithotripsy (ESWL) success. These variables may be categorized as stone variables, patient variables and operator variables. Only multivariate analysis on a large number of homogenous patients may offer an objective evaluation of the factors conditioning ESWL outcome. PMID- 17726353 TI - Metaphylaxis of nephrolithiasis. AB - The introduction of extracorporeal shockwave lithotripsy (ESWL), with its noninvasive removal of stones and considerable reduction in the morbidity of stone disease, has revolutionized the therapy of urolithiasis. Unfortunately the propensity for stone recurrence is not altered by removal of stones with ESWL and stone recurrence is still about 50%. Progress in medical treatment has shown how different therapies can prevent the stone recurrence, even though it is often difficult to predict which patient will go on to become a recurrent stone former. With the right evaluation, however, the cause of calculi formation can be treated in 97% of the patients. Primary prevention of urolithiasis includes general prophylaxis in a no-risk population that has never been affected by urinary tract stones, is without familial predisposition, metabolic or genetic alterations, or urinary tract abnormalities or infections and who live in a geographical area that is at risk. Secondary prevention or metaphylaxis of stone disease is aimed at the population at risk, that is patients already affected by the stone disease, with familial predisposition, with urinary tract alterations, with metabolic or genetic alterations (gout, bone or bowel diseases) and urinary infection. PMID- 17726355 TI - Predictive items of one-year mortality in nonagenarians. The NonaSantfeliu Study. AB - BACKGROUND AND AIMS: Few studies have prospectively evaluated predictors of mortality in nonagenarian cohorts. Our objective was to determine a set of predictors of all-cause mortality in a cohort of nonagenarians after one year of follow-up. METHODS: 186 nonagenarians were evaluated prospectively, 137 of whom lived in their own homes (74%) and 49 (26%) were institutionalized. Functional status was determined by the Lawton-Brody (LI) and Barthel Index (BI), and cognition by the Spanish version of the Mini Mental State Examination (MEC). The Charlson score was used to measure global comorbidity. Nutritional status was evaluated by the short version of the Mini Nutritional Assessment questionnaire (short- MNA). RESULTS: The sample was composed of 143 women (76.5%) and 43 men, with a mean age of 93.06 (3.1) years. The rate of mortality was 19.3%. There were no differences in mortality between men and women. Although the BI and LI were both related to 1-year mortality in bivariate, unadjusted analysis, their contribution was minimal in multivariate analyses. Age, heart failure and short MNA remained associated with mortality in the multivariate analyses. CONCLUSIONS: This study supported the importance of age, heart failure and nutritional status in predicting 1- year mortality in nonagenarians. PMID- 17726354 TI - Types of anemia and mortality among older disabled women living in the community: the Women's Health and Aging Study I. AB - AIMS: To classify the different types of anemia among moderately to severely disabled women living in the community and examine the relationship between types of anemia and mortality. METHODS: We studied anemia in 688 women, >or=65 years, in the Women's Health and Aging Study I, a population based study of moderately to severely disabled older women living in the community in Baltimore, Maryland. Anemia was defined by World Health Organization criteria. Causes of anemia were classified as due to nutritional deficiencies (iron, folate, and B12 deficiencies), anemia of chronic inflammation, anemia with renal disease, and unexplained anemia. RESULTS: 147 of 688 (21.4%) women were anemic (hemoglobin <12 g/dL). Of the 147 anemic women, 22 (15.0%) had anemia due to nutritional causes, 45 (30.6%) had anemia due to chronic inflammation, 29 (19.7%) had anemia and renal disease, and 51 (34.7%) had unexplained anemia. The proportions of those who died over five years among non-anemic women and women with anemia due to nutritional causes, chronic inflammation, renal disease, and unexplained anemia were 26.1%, 18.2%, 38.6%, 64.3%, and 33.3%, respectively (p<0.0001). Compared with non-anemic women, those with anemia and renal disease (HR 1.99, 95% CI 1.18 3.35, p=0.009) and anemia of chronic inflammation (HR 1.69, 95% CI 1.00-2.84, p=0.05) had higher risk of death. CONCLUSIONS: Anemia is common among moderately to severely disabled older women living in the community, and about one-third of the anemia is unexplained. Anemia with renal disease and anemia of chronic inflammation are associated with a higher mortality. PMID- 17726356 TI - Incidence of fractures and changes over time among the aged in a Finnish municipality: a population-based 12-year follow-up. AB - BACKGROUND AND AIMS: The incidence of fractures is high in older populations. The aim of this study was to describe the incidence of different fractures and to analyse the changes in age-adjusted yearly incidences among older persons. METHODS: A prospective true cohort design. Information about fractures in 482 men and 695 women aged 65 or over living in the municipality of Lieto, south-western Finland, was collected from 1991 until 2002. Poisson's regression model was used to analyse changes in yearly incidences. RESULTS: During 10,040 person years (PY) of follow-up, 307 (26%) persons sustained 425 fractures. The total incidence rate of fractures was 53.4 per 1000 PY (95% confidence intervals: 47.9-59.5) in women, and 24.9 per 1000 PY (20.4-30.4) in men. The age-specific incidence of fractures increased with age in both genders. Rates of hip and wrist fractures tended to be higher in women. 7.2% subjects sustained two or more fractures during follow- up. The majority of fractures resulted from a fall, and only 3.5% were caused by extremely serious accidents. No significant changes in the age-adjusted incidences of all fractures were found in either gender during follow-up. CONCLUSION: Fractures are common in the aged population, and the incidence of most types of fracture is associated with increasing age. Only a minority of fractures are caused by extremely serious accidents. No significant changes in the age-adjusted yearly incidences of fractures were observed in this aged cohort during a 12-year follow-up. PMID- 17726357 TI - Effect of co-morbidity on the association of high body mass index with walking limitation among men and women aged 55 years and older. AB - BACKGROUND AND AIMS: Obesity among older persons is rapidly increasing, thus affecting their mobility negatively. The aim of this study was to examine the association of high body mass index (BMI) with walking limitation, and the effect of obesity-related diseases on this association. METHODS: In a representative sample of the Finnish population of 55 years and older (2055 women and 1337 men), maximal walking speed, chronic diseases, and BMI were ascertained in a health examination. Walking limitation was defined as maximal walking speed of less than 1.2 m/s or difficulty in walking 500 meters. To analyze the effects of chronic conditions, smoking, marital status, and education on BMI class differences in walking limitation, covariates were sequentially adjusted in logistic regression analyses. RESULTS: In women, an increasing gradient in the age-adjusted risk of walking limitation was observed with higher BMI: overweight (OR 1.47, 95% CI 1.10 1.96), obese (OR 2.77, 95% CI 2.01-3.82), and severely obese (OR 5.80, 95% CI 3.52-9.54). In men, the risk was significantly increased among the obese (OR 1.63, 95% CI 1.04-2.55) and severely obese (OR 4.33, 95% CI 2.20- 8.53). After adjustment of multiple covariates, the association remained significant among the obese (OR 1.99, 95% CI 1.38-2.86) and severely obese women (OR 3.64, 95% CI 2.12 6.26), as well as severely obese men (OR 2.78, 95% CI 1.30-5.95). Knee osteoarthritis in women and diabetes in men contributed most to the excess risk of walking limitation among obese persons, 18 and 32% respectively. CONCLUSIONS: Obesity increases the risk of walking limitation, independent of obesity-related diseases, smoking, marital status, and education, especially in older women. The results of this study emphasize the importance of maintaining normal body weight, in order to prevent obesity-related health risks and loss of functioning in older age. PMID- 17726359 TI - Is overweight/obesity associated with short sleep duration in older women? AB - BACKGROUND AND AIM: No study to date has documented the association between short sleep duration and the risk for obesity in older people. Therefore, the aim of this study was to examine cross-sectional associations between short sleep duration and variations in body fat indices in older women. METHODS: Anthropometric and body composition measurements, resting energy expenditure, daily energy expenditure, daily energy intake, plasma lipid-lipoprotein profile, and self-reported sleep duration were determined in a sample of 90 women of 50 years and above. RESULTS: The odds ratios for overweight/obesity were comparable in subjects reporting <7 hours and >or=7 hours of sleep per day, with or without adjustment for age, daily energy expenditure and daily energy intake. The results did not permit to observe any significant difference between the two sleeper groups for all the variables investigated. The correlations between sleep duration and adiposity indices were also non significant. CONCLUSIONS: Short sleep duration does not predict an increased risk of being overweight/obese in older women. This observation, together with our previously reported results in younger subjects, suggests that the sleep-body fat relationship progressively becomes less detectable with increasing in age. PMID- 17726358 TI - Admission albumin levels and functional outcome of elderly hip fracture patients: is it that important? AB - BACKGROUND AND AIMS: Low serum albumin level is considered a marker of poor health outcome in various medical conditions. A relationship between low albumin levels and poor functional outcome has been found in the elderly, lower albumin predicting a greater functional decline. The objective of this study was to evaluate to what extent admission albumin levels may affect the functional outcome of elderly hip fracture patients. METHODS: This retrospective chart review study was conducted in an orthogeriatric unit of a university-affiliated referral hospital. The participants were 449 elderly patients with hip fractures, admitted for a standard rehabilitation course. Functional outcome of patients with normo-albuminemia and hypo-albuminemia was assessed by Functional Independence Measurement (FIM) at admission and discharge. Data were analyzed by t-test, Pearson's correlation, Chi-square test and Linear Regression. RESULTS: 38.8% of patients were hypoalbuminemic upon admission. These patients were older (p<0.001) and had lower Mini-Mental State Examination (MMSE) scores (p=0.003), compared with normo- albuminemic patients. Discharge FIM scores were higher in normo-albuminemic compared with hypo-albuminemic patients (total FIM 86.1+/-23.9 and 77.0+/-26.4, respectively; p<0.001; motor-FIM 60.0+/-16.3 and 53.4+/-18.0, respectively; p<0.001). Linear regression analysis showed that total FIM at discharge was inversely associated with pre-fracture function (beta -0.13; p<0.001). A high MMSE score (beta 0.16; p<0.001), female gender (beta 0.05; p=0.02) and higher admission total FIM scores (beta 0.69; p<0.001) emerged as predictors of higher total FIM scores upon discharge. Albumin levels did not independently predict better total FIM scores upon discharge (beta -0.02; p=0.36). CONCLUSIONS: Normo-albuminemic patients present with better admission FIM scores and have higher discharge FIM scores. After controlling for possible confounders, albumin remains a non-significant predictor of higher discharge FIM scores. We suggest that low albumin levels should not be considered as adversely affecting the rehabilitation of elderly hip fracture patients. PMID- 17726360 TI - Assessment of sarcopenia: longitudinal versus cross sectional body composition data. AB - BACKGROUND AND AIMS: An accurate diagnosis of sarcopenia is required. The aim of this study is to correlate the results of two methods to define sarcopenia using cross sectional body composition data, with actual loss of fat free mass. METHODS: Healthy older subjects (926 females and 381 males aged 70 years or more) and healthy young adults (425 females and 151 males aged 20 to 40 years) were studied. Body composition was assessed by double beam X ray absorptiometry (DEXA). Among older subjects, a contemporary subsample of 148 females and 45 males had two or more measurements, separated by 4.8+/-1.5 years and loss of fat free mass per year was calculated. In the whole sample, total and appendicular lean body mass index were calculated as total or appendicular lean body mass/height. Using data from young people, sex specific t scores were obtained. In older subjects residuals were derived from a regression equation, using total or appendicular fat free mass as the dependent variable and height, fat free mass and age as independent variables. RESULTS: The concordance between residuals and t scores to define sarcopenia was 68 and 72%, respectively. Among subjects with two or more measurements, men and women lost a mean of 521+/-454 and 221+/-399 g/year of fat free mass, respectively. The odds ratio of losing more than 822 g lean body mass /year among men or 514 g lean body mass /year among women was 2.63 and 2.64 for subjects classified in the two lowest quintiles of sarcopenia, using t scores or residuals, respectively. CONCLUSIONS: Cross sectional body composition data can predict loss of fat free mass among older people. PMID- 17726362 TI - Effects of a one-year exercise training program in adults over 70 years old: a study with a control group. AB - BACKGROUND AND AIMS: Exercise training is known to improve exercise tolerance in elderly subjects. Therefore the present study aimed at investigating the effects of one year of combined endurance and resistance training in healthy older people. METHODS: After baseline evaluation, subjects were assigned to either the training group (n=24, age 77.2+/-3.6) or the control group (n=16, age 76.1+/ 4.8). Subjects in the control group did not change anything in their everyday activities, whereas subjects in the training group underwent moderately intensive combined exercise training, 3 hours a week over the course of one year. Breath-by breath oxygen uptake and heart rate were measured at each workload during the symptom-limited cardiopulmonary exercise test. Performance on the 6-minute (6 MWT) and 200-meter (200-MWT) walk tests was registered and maximal strength was measured on knee extensor and plantar flexor muscles. RESULTS: After training, oxygen uptake was significantly increased, both at the ventilatory threshold (+11.6%, p<0.01) and at the end of exercise (+14.8%, p<0.001). The distance walked in 6 min (+10%, p<0.001), the time required to cover 200 m (-7.3%, p<0.001) and the maximal muscle strength (+15.2% and +17.4% for knee extensors and plantar flexors respectively, p<0.05) also improved after training. All these parameters had not significantly changed in the control group after the one-year period. CONCLUSIONS: The results of the present study show that one year of combined exercise training is well-tolerated and improves aerobic capacity, performance on field tests and muscle strength in healthy subjects over 70 years old. PMID- 17726361 TI - Old women with a recent fall history show improved muscle strength and function sustained for six months after finishing training. AB - BACKGROUND AND AIMS: Restricted physical activity as a consequence of chronic disease or injury is a predictor of functional decline. The aim of this study was to test the hypothesis that a 6- month multidimensional training program would have sustained beneficial effects upon the physiological, functional and psychological condition of old women with a recent history of falls. METHODS: Participants were 65 home-dwelling women (70-90 years) identified from hospital records as having had an accidental fall. After assessment of muscle strength, balance performance, walking speed, balance confidence, and physical activity level, the participants were randomly assigned to a control group (n=33) or a training group (n=32), who performed a multidimensional training program including moderate resistance exercise and balance exercise twice weekly for 6 months. Measurements were repeated after 6 and 12 months. RESULTS: Six months of multidimensional training resulted in significant improvements and between-group differences in isometric knee extension strength (p<0.05), trunk extension/ flexion strength (p<0.001), habitual/maximal walking speed (p<0.001) and balance performance (p<0.001). At follow-up, 6 months after intervention, these improvements were preserved in the training group and there was also a significant between- group difference with regard to balance confidence. No between-group differences were found concerning number of falls or physical activity level during the one-year study period. CONCLUSIONS: A multi-dimensional training program produced significant improvements in physiological and functional risk factors for falls and disability in women aged 70-90 years with a recent history of falls. PMID- 17726363 TI - Cognitive stimulation intervention for elders with mild cognitive impairment compared with normal aged subjects: preliminary results. AB - BACKGROUND AND AIMS: Cognitive training programs have been developed for Alzheimer's disease patients and the healthy elderly population. Collective cognitive stimulation programs have been shown to be efficient for subjects with memory complaint. The aim of this study was to evaluate the benefit of such cognitive programs in populations with Mild Cognitive Impairment (MCI). METHODS: Twelve patients with MCI and twelve cognitively normal elders were administered a cognitive stimulation program. Cognitive performance (Logical Memory, Word paired associative learning task, Trail Making Test, verbal fluency test) were collected before and after the intervention. A gain score [(post-score - pre-score)/ pre score] was calculated for each variable and compared between groups. RESULTS: The analysis revealed a larger intervention size effect in MCI than in normal elders' performances on the associative learning task (immediate recall: p<0.05, delayed recall: p<0.01). The intervention was more beneficial in improving associative memory abilities in MCI than in normal subjects. At the end of the intervention, the MCI group had lower results than the normal group only for the delayed recall of Logical Memory. CONCLUSIONS: Although further studies are needed for more details on the impact of cognitive stimulation programs on MCI patients, this intervention is effective in compensating associative memory difficulties of these patients. Among non-pharmacological interventions, cognitive stimulation therapy is a repeatable and inexpensive collective method that can easily be provided to various populations with the aim of slowing down the rate of decline in elderly persons with cognitive impairment. PMID- 17726364 TI - Variations in quality of Home Care between sites across Europe, as measured by Home Care Quality Indicators. AB - BACKGROUND AND AIMS: The increase in the proportion of elderly people and a consequent increase in the demand for care have caused healthcare systems to become overloaded. This paper describes the use of Home Care Quality Indicators (HCQIs), derived from the Minimum Data Set for Home Care, for monitoring quality of care. Research questions were, "Do HCQI scores vary between home care organizations in different countries?" and "Are one or more country-specific sites consistently scoring better on most or all HCQIs"? METHODS: a cross sectional observational study of 65+ randomly selected clients of home care organizations in urban areas in 11 European countries who had been receiving home care for at least two weeks. Data were collected with the MDS-HC. The scoring of 16 prevalent quality indicators for home care, adjusted for population differences, was calculated with baseline data. RESULTS: Population size at baseline was 4,007 clients. Among home care clients in Europe, "rehabilitation potential in Activities of Daily Living and no therapies" (average 75.9%) and "inadequate pain control" were the most common quality problems. The prevalence between populations studied in various countries varied substantially. No country specific site consistently scored worst or best. CONCLUSIONS: HCQIs derived from the MDS-HC detect variance in quality scores between home care in the 11 partner countries. The highest prevalence of unwanted outcomes were most often found in the Czech Republic, Italy and Germany. Although further research is necessary, we believe that HCQIs may be of great value for quality improvement in home care. PMID- 17726365 TI - Strontium ranelate normalizes bone mineral density in osteopenic patients. AB - AIMS: To assess the capacity of strontium ranelate to restore normal bone mineral density (WHO definition: T-score >or=-1) in post-menopausal osteopenic women (T score between -1 and -2.5) at baseline. METHODS: Post-hoc analysis from SOTI and TROPOS studies of 1428 patients randomly assigned to receive either 2 g of strontium ranelate a day or placebo for three years. Bone mineral density was measured at baseline and each year for three years. Results were analyzed on an intention-to-treat basis. RESULTS: At lumbar spine, after one, two and three years of treatment with strontium ranelate, 26.4, 42.1 and 58.2% respectively of osteopenic patients normalized their bone mineral density, compared with 6.6, 8.9 and 11.9% in the placebo group (all p<0.001). At total hip, the percentage of patients normalizing their bone mineral density was 5.4, 10.0 and 19.6% in the strontium ranelate group and 1.8, 1.4 and 1.6% in the placebo one (all p<0.001). CONCLUSION: Strontium ranelate is able to normalize bone mineral density in a significant proportion of osteopenic patients after one, two and three years of treatment. The clinical relevance of these results should be confirmed by direct demonstration of the anti-fracture efficacy of strontium ranelate in osteopenic patients. PMID- 17726366 TI - An overview of stress urinary incontinence treatment in women. AB - Stress urinary incontinence (SUI) is common in women, but it is under-reported and under-treated. We review here the management of SUI in women. Pelvic floor muscle training treats SUI in the majority of female patients, whereas anti-SUI devices are not widely accepted. Duloxetine has been approved for treating SUI. Suburethral slings have revolutionized the surgical management of SUI with durable efficacy, in contrast with injectable bulking agents. PMID- 17726367 TI - P21(WAF1/CIP1) may be a tumor suppressor after all. AB - The cyclin-dependent kinase inhibitor p21WAF1/CIP1 was originally considered to be a tumor-suppressor because it was identified as a key mediator of p53 dependent cell cycle arrest. However, it has been suggested that p21 may also act as an oncogene because it often inhibits apoptosis. For example, deletion of p21 from p53-deficient mice resulted in longer survival and in a significantly reduced number of thymic lymphomas that was explained by higher apoptotic rates in these mice. However, recently it has been shown that a p53 mutant that had lost its ability to induce apoptosis, but retained its ability to induce p21 and cell cycle arrest, was able to suppress lymphomagenesis in different cancer models. Tumor suppression by this p53 mutant was modulated by p21, which induced senescence and preserved chromosomal stability. These data suggest that the ability of p21 to induce cell-cycle arrest may lead to tumor suppression in some types of cancer. PMID- 17726368 TI - Antitumor effects of a natural anthracycline analog (Aloin) involve altered activity of antioxidant enzymes in HeLaS3 cells. AB - The antiproliferative and cytotoxic potential of the natural anthracycline aloin from Aloe vera was tested on human uterine carcinoma HeLaS3 cells. Aloin showed a pronounced antiproliferative effect at physiological concentration (IC50 = 97 microM), caused cell cycle arrest in the S phase and markedly increased HeLaS3 cell apoptosis (to 24%). In the concentration range of 20-100 microM, its action was accompanied by remarkable changes in the activity of almost all antioxidant enzymes: MnSOD activity was increased many fold, while CuZnSOD and iNOS activities were inhibited. Moreover, inhibition of CuZnSOD was shown to occur by direct aloin interaction with the enzyme. As catalase activity was not changed, it is suggested that such conditions were responsible for antiproliferative and cytotoxic effects owing to accumulation of H2O2. Aloin alone was a more potent proapoptotic agent than a 2 Gy fractional dose of ionizing radiation or a combination of the two. Compared to other currently used therapeutics, aloin, due to its less undesirable side effects and antimetastatic potential, may prove to be the agent of choice on which clinical protocols for the treatment of human cervical carcinoma should rely in future. PMID- 17726369 TI - Neuropilin-1 interacts with integrin beta1 and modulates pancreatic cancer cell growth, survival and invasion. AB - Neuropilin-1 (Np-1) is a coreceptor for vascular endothelial growth factor-A (VEGF-A), and both are expressed at high levels in pancreatic ductal adenocarcinomas (PDACs). While VEGF-A has been implicated in tumor angiogenesis, the role of Np-1 in PDAC is less clearly defined. Accordingly, PANC-1 pancreatic cancer cells, which express relatively high levels of Np-1, were transfected with the Np-1 antisense cDNA. By comparison with sham transfected cells, Np-1 antisense expressing clones (Np-1AS) exhibited decreased anchorage independent growth, adhesion and invasiveness, and prolonged doubling times. Np-1AS were also more sensitive to the pro-apoptotic actions of ActD, as evidenced by PARP cleavage, caspase 9 activation and annexin V staining. ActD decreased Bcl-xL and STAT5 levels in the antisense expressing cells, but not in sham-transfected cells, and did not alter STAT3, Bcl-2, phospho-AKT, AKT, Bad, Bax or Bak levels. Immunoprecipitation followed by immunoblotting revealed that Np-1 associated with integrin beta1 and integrin beta1 blockade attenuated adhesion. However, Np-AS expressing clones exhibited enhanced tyrosine phosphorylated focal adhesion kinase. Thus, Np-1 confers a growth and survival advantage to PANC-1 cells, and interacts with integrin beta1 to coordinate signaling events that promote cell adherence and invasiveness. PMID- 17726370 TI - Regulation of arginine methylation in endothelial cells: role in premature senescence and apoptosis. AB - With the recent characterization of enzymes responsible for protein arginine methylation and demonstration that catabolic products of arginine methylation, such as asymmetric dimethylarginine (ADMA), are among the most powerful mechanisms of atherogenesis, developing endothelial dysfunction and cardiovascular complications in a variety of pathologic processes, the need for functional characterization of the methylation-demethylation processes becomes ever more urgent. Therefore, the aims of the present study were to refine the feedback regulation of protein arginine methylation using one of the heavily methylated proteins, an RNA-binding protein Sam68, as a prototype, to elucidate the relations between Sam68 methylation and tyrosine phosphorylation and the role of methylation in RNA binding and subcellular distribution, as well as the cellular consequences of reduced protein methylation. Screening pro-atherogenic substances known to induce endothelial dysfunction showed that ADMA did not affect the level of arginine methylation of Sam68, whereas peroxynitrite was a strong inhibitor of methylation. Advanced glycation-modified collagen I, which accumulates in diabetes and induces formation of peroxynitrite and premature endothelial cell senescence, also inhibited arginine methylation of Sam68. When the level of arginine methylation of Sam68 was pharmacologically reduced, this did not affect its RNA binding or degree of tyrosine phosphorylation, but resulted in the predominantly nuclear hypomethylation pattern. Furthermore, protein hypomethylation resulted in the increased rate of apoptosis and premature senescence. This data may offer an additional explanation for the proapoptotic and senescence-accelerating action of peroxynitrite, a potent inhibitor of protein methylation. PMID- 17726371 TI - Control of stress-regulated gene expression and longevity by the Sch9 protein kinase. AB - Cell growth and progression through the cell cycle is finely tuned by nutrient availability and stress in eukaryotic cells. In yeast, the Sch9 protein kinase has been identified as a central regulator of longevity and stress resistance. Recent work revealed that Sch9 plays critical roles in transcriptional activation dependent on the environmental conditions. Favorable growth conditions stimulate the expression of genes related to ribosomal function by direct targeting of Sch9 by the TOR kinase, whereas under osmostress conditions, Sch9 plays a direct role in the activation of stress defense genes. At least upon stress, Sch9 seems to activate transcription directly at the chromatin structure. Therefore we speculate that targeting of the kinase to chromatin might coordinate transcription dependent on environmental stimuli and be responsible for the functions of Sch9 in life span regulation and adaptation to stress. PMID- 17726372 TI - DNA damage-induced accumulation of centrosomal Chk1 contributes to its checkpoint function. AB - The checkpoint kinase Chk1 is an established transducer of ATR- and ATM-dependent signalling in response to DNA damage. In addition to its nuclear localization, Chk1 localizes to interphase centrosomes and thereby negatively regulates entry into mitosis by preventing premature activation of cyclin B-Cdk1 during unperturbed cell cycles. Here, we demonstrate that DNA damage caused by ultraviolet irradiation or hydroxyurea treatment leads to centrosomal accumulation of endogenous Chk1 in normal human BJ fibroblasts and in ATR- or ATM deficient fibroblasts. Chemical inhibition of ATR/ATM by caffeine led to enhanced centrosomal Chk1 deposition associated with nuclear Chk1 depletion. In contrast to normal or ATM-deficient fibroblasts, genetically ATR-deficient Seckel fibroblasts showed detectable constitutive centrosomal accumulation of Chk1 even in the absence of exogenous insults. After DNA damage, the centrosomal fraction of Chk1 was found to be phosphorylated at ATR/ATM phosphorylation sites. Forced immobilization of kinase-inactive but not wild-type Chk1 to centrosomes resulted in a G2/M checkpoint defect. Finally, both DNA damage, and forced centrosomal expression of Chk1 in the absence of genotoxic treatments induced centrosome amplification in a subset of cells, a phenomenon which could be suppressed by inhibition of ATM/ATR-mediated signaling. Taken together, our results suggest that accumulation of phosphorylated Chk1 at centrosomes constitutes an additional element in the DNA damage response. Centrosomal Chk1 induces G2/M cell cycle arrest and may evoke centrosome amplification, the latter possibly providing a backup mechanism for elimination of cells with impaired DNA damage checkpoints operating earlier during the cell cycle. PMID- 17726373 TI - Non-canonical activation of GLI transcription factors: implications for targeted anti-cancer therapy. AB - GLI transcription factors constitute the final effectors of the Hedgehog (HH) signaling pathway. In many tumors, such as those of the pancreas, prostate, skin or lung, ectopic activation of GLI proteins has been linked to tumorigenesis. In several of these cases, HH ligand- or receptor-induced signaling (canonical HH signaling) was found to be the cause underlying GLI activation. Recent evidence points towards additional, noncanonical, mechanisms of GLI activation. Here we review findings on the crosstalk of two HH-unrelated signaling pathways (RAS and Transforming growth factor beta) to the HH pathway downstream of the signaling component Smoothened. Both pathways stimulate and/or induce GLI1 and GLI2 activity independent of the presence of HH ligands. We also discuss the putative roles of these crosstalk mechanisms for tumor cell metastasis. The emerging picture of GLI transcription factors as an integrative platform of numerous signaling inputs has important implications for the understanding of tumor development and argues for inclusion of targets acting downstream of the receptor level in the design of current drug development programs. PMID- 17726374 TI - Human Kid is degraded by the APC/C(Cdh1) but not by the APC/C(Cdc20). AB - The APC/C(Cdh1) (anaphase promoting complex/cyclosome) targets numerous cell cycle proteins for ubiquitin mediated degradation in late mitosis and G1. The KEN box is one of two major recognition motifs of APC/C(Cdh1) substrates. This motif is however very common and shared by a tenth of the human proteome, the vast majority of which are obviously not APC/C substrates. We have observed that most known functional KEN boxes are followed by a proline residue and show that this proline plays a role in APC/C(Cdh1) specific degradation. This insight can be instrumental for identifying novel APC/C(Cdh1) substrates. We used this KENxP motif to identify human Aurora B and Kid as APC/C(Cdh1) substrates. The degradation of Xenopus XKid at metaphase by APC/C(Cdc20) is essential for chromatid segregation. Human Kid in contrast is degraded later and its APC/C(Cdh1) specific degradation is not required for mitotic progress. It is thus likely that Kid inactivation in G1 takes place both by nuclear sequestration and degradation by the APC/C(Cdh1). PMID- 17726375 TI - Telomere length profiles in humans: all ends are not equal. AB - Telomere length is an important parameter of telomere function since it determines number of aspects controlling chromosome stability and cell division. Since telomeres shorten with age in humans and premature aging syndromes are often associated with the presence of short telomeres, it has been proposed that telomere length is also an important parameter for organismal aging. How mean telomere lengths are determined in humans remains puzzling, but it is clear that genetic and epigenetic factors appear to be of great importance. Experimental evidence obtained from many different organisms has provided the basis for a widely accepted counting mechanism based on a negative feedback loop for telomerase activity at the level of individual telomeres. In addition, recent studies in both normal and pathological contexts point to the existence of chromosome-specific mechanisms of telomere length regulation determining a telomere length profile, which is inherited and maintained throughout life. In this review, we recapitulate the available data, propose a synthetic view of telomere length control mechanisms in humans and suggest new approaches to test current hypotheses. PMID- 17726376 TI - Resveratrol: from basic science to the clinic. AB - Plants produce an extraordinary array of low molecular mass natural products endowed with biological activity. Among these molecules, resveratrol (3,5,4' trihydroxystilbene) has been identified as an inhibitor of carcinogenesis with a pleiotropic mode of action. Extensive literature on its anticancer activity, performed in cellular models, suggests a potential antiproliferative and apoptogenic use of the stilbene. Similarly, studies on implanted cancers and chemical-induced tumors confirm a potential chemotherapeutical interest of the compound. Moreover, recent intriguing studies have demonstrated, in mice, that the negative effects (insulin resistance and hyperglycemia) of a high-fat diet might be prevented by resveratrol treatment. Despite these promising observations, only few clinical trials have been performed on the compound due to the scarce interest of pharmaceutical industry. We suggest that resveratrol might be considered an interesting compound in association with more specific target oriented drugs. PMID- 17726377 TI - Mitochondrial protein import: a matter of death? AB - Mitochondria play a central role not only in energy generation but also for apoptosis. A key step in mitochondrial apoptosis is the release of mitochondrial proteins, most importantly cytochrome c. This release is orchestrated by the pro- and anti-apoptotic members of the Bcl-2 protein family. The functions of these Bcl-2 family members are clear in terms of order and of principle: the pro apoptotic BH3-only protein group contains the triggers, which cause the activation of the effectors Bax and Bak, while the anti-apoptotic Bcl-2-like proteins prevent this activation. However, the molecular details are still insufficiently clear and the proposed models have certain gaps and are partly contradictory. We have recently presented evidence that targeting to mitochondria of at least one BH3-only protein is essential for its pro-apoptotic functions. Here we discuss how this mechanism might fit into and expand existing models and speculate about the potential implications of this finding. PMID- 17726378 TI - Aurora B kinase activity is required to prevent polar cortical ingression during cytokinesis. AB - Cytokinesis requires proper regulation of microtubule dynamics. It has been suggested that dynamic astral microtubules prevent cortical ingression. However, it remains unknown how astral microtubules maintain their dynamic state. Here we show that aurora B kinase, a component of the chromosome passenger complex, is required to sustain the dynamic state of astral microtubules during cytokinesis. Treatment of HeLa cells with Hesperadin, an inhibitor of aurora B kinase, caused abnormal cortical protrusion, leading to cortical ingression in the protruding region and cytokinesis failure. Actin filaments, myosin II, and RhoA failed to localize at the equator but instead distributed along the lateral and/or polar cortex in cells treated with Hesperadin. Time-lapse analyses of microtubule dynamics showed that, in cells treated with Hesperadin, abnormally bundled astral microtubules targeted the protruding region. Mitotic kinesin-like protein 1 (MKLP1), a component of the spindle midzone required for bundling of microtubules, was not detected along bundled astral microtubules in cells treated with Hesperadin, suggesting that factors other than MKLP1 may be involved in this process. Our results suggest that aurora B kinase activity is required for proper regulation of microtubule dynamics to ensure that cytokinesis occurs precisely at the cell equator. PMID- 17726379 TI - Beta2-chimaerin in cancer signaling: connecting cell adhesion and MAP kinase activation. AB - The chimaerins are Rac GTPase-activating proteins that bind diacylglycerol. Emerging evidence implicates beta2-chimaerin in tumor progression. Here, we discuss our recent work in Drosophila melanogaster in the context of previous studies performed in human cancer cell lines that together lend new mechanistic insight into the role of chimaerins in cancer. PMID- 17726380 TI - Turning the tables: Myc activates Wnt in breast cancer. AB - Previous molecular and genetic data implicate the c-myc gene as a critical downstream effector of the Wnt/TCF pathway in colon cancer. However, the involvement of c-myc in mammary epithelial cell transformation had not been explored. We recently showed that c-Myc induces a profound morphological transformation in human mammary epithelial cells accompanied by anchorage independent growth. The mechanism of c-Myc transformation was revealed in part through the finding that, in contrast to colon cancer, c-Myc activates the Wnt pathway and endogenous TCF activity by suppressing the Wnt inhibitors DKK1 and SFRP1. Notably, DKK1 and SFRP1 were found to be strongly suppressed in human breast cancer cell lines, and their re-expression inhibited the transformed phenotype. We demonstrated that breast cancer cells become dependent on repression of the Wnt inhibitors for cell proliferation, i.e. they have acquired an "oncogene addiction", suggesting that the Myc-Wnt pathway is an attractive therapeutic target. We propose that a positive feedback loop of c-myc and Wnt signaling operates in breast cancer. PMID- 17726381 TI - Interaction between the Cdk2/cyclin A complex and a small molecule derived from the pRb2/p130 spacer domain: a theoretical model. AB - Retinoblastoma (RB) family proteins pRb, p107 and pRb2/p130 are important cellular factors which play a well-recognized role as tumor and growth suppressors. These proteins are actively involved in the negative control of the cell cycle and their function is modulated via complex homeostatic processes, most of them involving post-translational regulation of their phosphorylation status. Interestingly, the family members p107 and pRb2/p130 share the ability to physically interact and inhibit the kinase activity of the Cdk2/Cyclin A and Cdk2/Cyclin E complexes. Regarding pRb2/p130, its inhibitory effect on Cdk2/Cyclin A activity has been attributed to the "spacer" region. Recently, a 39 aa-long pRb2/p130 spacer-derived peptide (Spa310, aa 641-679) was selected as the sequence responsible for Cdk2/Cyclin A inhibition. Following the identification of this active sequence, here we propose a computer-generated three-dimensional model of the interaction between the Cdk2/Cyclin A complex and the N-terminal nine-amino acid sequence of the Spa310 peptide. We believe this model to be useful for the rational development of peptide or peptidomimetic kinase inhibitors for negative cell cycle modulation in cancer cells. PMID- 17726382 TI - The role of Gas1 in embryonic development and its implications for human disease. AB - Growth Arrest Specific Gene 1 (Gas1) has long been regarded as a cell cycle inhibitor of the G(0) to S phase transition. How GAS1, a GPI-anchored plasma membrane protein, directs intracellular changes without an extracellular ligand or a transmembrane protein partner has been puzzling. A recent series of biochemical and molecular genetic studies assigned the mammalian Hedgehog (HH) growth factor to be a ligand for GAS1 in vitro and in vivo. HH has enjoyed considerable attention for its profound role in embryonic patterning as a classic morphogen, i.e. inducing various cell types in a concentration-dependent manner. GAS1 appears to help transform the HH concentration gradient into its morphogenic activity gradient by acting cooperatively with the HH receptor, the 12 transmembrane protein Patched 1 (PTC1). These findings provoke intriguing thoughts on how HH and GAS1 may coordinate cell proliferation and differentiation to create biological patterns. The role of HH extends to human genetic diseases, stem cell renewal, and cancer growth, and we consider the possibility of GAS1's involvement in these processes as well. PMID- 17726383 TI - Physician supply revisited. PMID- 17726384 TI - New directions for nurse practitioners and physician assistants in the era of physician shortages. AB - During the past 35 years, the roles for nurse practitioners (NPs) and physician assistants (PAs) have evolved in parallel with the roles that physicians have come to play. Shifting needs in primary care and expanding opportunities in specialty medicine have been the dominant trends. Future directions will be influenced additionally by the deepening physician shortage. NPs are preparing for this future by developing doctoral-level training programs in comprehensive care, whereas PAs are adding training opportunities in specific specialties. Yet, neither discipline has expanded its training capacity to the degree that will be required, and, like physicians, neither will have a supply of practitioners that will match future demand. Coordinated planning to increase the educational infrastructure for physicians, NPs, and PAs is essential. PMID- 17726385 TI - The history, purpose, and future of instruction in the responsible conduct of research. AB - This article discusses the key decisions and steps that have partially formalized instruction in the responsible conduct of research (RCR) in U.S. research institutions, the different purposes for offering and/or requiring such instruction, and suggestions for what needs to be done to enhance the professional development of researchers in the future. RCR education has developed during three distinct eras: the 1980s, when policy makers were most concerned with defining and investigating research misconduct; the 1990s, when there was significant but highly decentralized growth in RCR instruction; and the years since 2000, when there have been a series of reforms and educational developments. There is still a need for scientists, universities, and professional societies to develop consensus on best ethical practices in many areas of scientific research. More also needs to be learned about assessing the quality of RCR instruction and the effects of training on researchers' behavior. To help set the course for RCR instruction in the future, more effort and funding need to be directed to studying actual research behavior and the factors that influence it; RCR educators and administrators must develop a common vocabulary and framework for developing and evaluating the impact of RCR instruction; and research institutions and funding agencies alike need to take a more active role in promoting and supporting RCR instruction. PMID- 17726386 TI - Prevention over cure: the administrative rationale for education in the responsible conduct of research. AB - The value of responsible conduct of research (RCR) education from an administrative perspective can be summed up in the oft-used adage, an ounce of prevention is worth a pound of cure. The National Academy of Sciences has underscored the importance of RCR education in three major reports relating public trust in research to the perception and reality of integrity within the field. Compliance and integrity cannot simply be hoped for. Rising numbers of reported cases of research misconduct support this view. This scenario calls for institutions to provide an environment where research integrity is a fundamental prerequisite. Supporting this notion is the adoption by federal oversight agencies of the compliance elements delineated in the Federal Sentencing Guidelines for Organizations as a guide for determining whether an institution promotes a culture of integrity. RCR education is most valuable to the administrator in raising the awareness of researchers regarding compliance and integrity issues and thereby reducing the risk of infraction. In turn, the overall level of confidence among users and supporters may be improved also. Therefore, RCR education has become a primary operational arm of administration in the quest for institutional stability. PMID- 17726387 TI - New graduate students' baseline knowledge of the responsible conduct of research. AB - PURPOSE: To assess (1) new biomedical science graduate students' baseline knowledge of core concepts and standards in responsible conduct of research (RCR), (2) differences in graduate students' baseline knowledge overall and across the Office of Research Integrity's nine core areas, and (3) demographic and educational factors in these differences. METHOD: A 30-question, computer scored multiple-choice test on core concepts and standards of RCR was developed following content analysis of 20 United States-published RCR texts, and combined with demographic questions on undergraduate experience with RCR developed from graduate student focus groups. Four hundred two new graduate students at three health science universities were recruited for Scantron and online testing before beginning RCR instruction. RESULTS: Two hundred fifty-one of 402 eligible trainees (62%) at three universities completed the test; scores ranged from 26.7% to 83.3%, with a mean of 59.5%. Only seven (3%) participants scored 80% or above. Students who received their undergraduate education outside the United States scored significantly lower (mean 52.0%) than those with U.S. bachelor's degrees (mean 60.5%, P < .001). Participants with prior graduate biomedical or health professions education scored marginally higher than new students, but both groups' mean scores were well below 80%. The mean score of 16 participants who reported previous graduate-level RCR instruction was 67.7%. Participants' specific knowledge varied, but overall scores were universally low. CONCLUSIONS: New graduate biomedical sciences students have inadequate and inconsistent knowledge of RCR, irrespective of their prior education or experience. Incoming trainees with previous graduate RCR education may also have gaps in core knowledge. PMID- 17726389 TI - Reported goals for responsible conduct of research courses. AB - PURPOSE: To identify existing responsible conduct of research (RCR) instructors' goals for RCR education. METHOD: E-mail requests were sent to the 116 recipients of National Institutes of Health (NIH) training grants awarded in 2000. Contacts were successfully made with 92 of the recipients, and 84 (91%) identified one or more RCR instructors for their grants. Of the 115 named instructors, 67 were correctly identified as RCR instructors and responded to our e-mail messages. RESULTS: Of the 67 instructors, 50 (75%) from 37 different institutions were interviewed. The reported goals were diverse: over 50 distinct goals were volunteered by the instructors. A secondary finding is that, despite having been identified by training grant directors as teachers of required RCR courses, nearly 25% of these individuals reported that they were not actually RCR instructors, and 22% of those interviewed were not aware that NIH trainees were required to take their courses. Further, whereas 80% of the respondents reported that RCR instruction was required for individuals other than NIH trainees, only 1 of the 50 reported that her/his course was required for all researchers within the institution. CONCLUSIONS: Identifying effective strategies for RCR education depends on first defining measurable outcomes based on well-defined goals. The findings of this study suggest a lack of consensus about those goals. In addition, the confusion about who teaches RCR courses and the rare expectation that RCR education is required for all researchers are disappointing reminders that RCR education is not universally viewed as central to research. PMID- 17726390 TI - What do mentoring and training in the responsible conduct of research have to do with scientists' misbehavior? Findings from a National Survey of NIH-funded scientists. AB - PURPOSE: The authors examine training in the responsible conduct of research and mentoring in relation to behaviors that may compromise the integrity of science. METHOD: The analysis is based on data from the authors' 2002 national survey of 4,160 early-career and 3,600 midcareer biomedical and social science researchers who received research support from the U.S. National Institutes of Health. The authors used logistic regression analysis to examine associations between receipt of separate or integrated training in research ethics, mentoring related to ethics and in general, and eight categories of ethically problematic behavior. Analyses controlled for gender, type of doctoral degree, international degree, and disciplinary field. RESULTS: Responses were received from 1,479 early-career and 1,768 midcareer scientists, yielding adjusted response rates of 43% and 52%, respectively. Results for early-career researchers: Training in research ethics was positively associated with problematic behavior in the data category. Mentoring related to ethics and research, as well as personal mentoring, decreased the odds of researchers' engaging in problematic behaviors, but mentoring on financial issues and professional survival increased these odds. Results for midcareer researchers: Combined separate and integrated training in research ethics was associated with decreased odds of problematic behavior in the categories of policy, use of funds, and cutting corners. Ethics mentoring was associated with lowered odds of problematic behavior in the policy category. CONCLUSIONS: The effectiveness of training in obviating problematic behavior is called into question. Mentoring has the potential to influence behavior in ways that both increase and decrease the likelihood of problematic behaviors. PMID- 17726392 TI - The CITI program: an international online resource for education in human subjects protection and the responsible conduct of research. AB - Since 2000, the Collaborative Institutional Training Initiative (CITI) program has evolved into an international resource for education in human subjects protection and the responsible conduct of research (RCR). More than 600,000 people at more than 715 institutions in dozens of countries have made use of CITI's online curricula. Although this Web-based resource was created in response to federal requirements for education in human subjects protection, the author's evaluation suggests that learners value and respond to the content in ways that transcend mere compliance. Recent expansion of the CITI model to address the RCR is motivated by such evidence, despite the absence of global federal requirement for RCR training. The authors give an overview of the CITI project, report and analyze evaluation data, and discuss the very idea of online education in research ethics. Although the authors exercise extreme caution in suggesting that CITI or any other four-hour curriculum will be causally related to any reduction in misconduct, they submit that when all members of the team are educated about common moral standards and appropriately mentored, the temptation for misbehavior by any one member is reduced, better science is promoted, and the public trust is preserved. At the very least, providing RCR education is a positive and useful means of reminding taxpayers and others that the same investigators who are spending their billions on research are simultaneously striving to ensure that integrity is woven into the fabric of the scientific enterprise. PMID- 17726393 TI - Scientific societies and promotion of the responsible conduct of research: codes, policies, and education. AB - Scientific societies have a significant opportunity to contribute to the promotion of responsible conduct of research (RCR) and to RCR education. The degree to which societies engage such opportunity spans a broad range. There are three principal ways RCR may be promoted by scientific societies. The first is through codes of conduct encouraging their membership to practice ethical research according to the tenets of these codes. The second is through specialized policies (e.g., publication practices) developed by scientific societies that help define normative behavior. Finally, societies have a role to play in creating materials and resources aimed at educating scientists and trainees in matters pertaining to proper research conduct. This article illustrates examples of each of these activities embraced by different scientific societies. The American Society for Microbiology is used as a specific example of a society that has been proactive in each of these three areas. Scientific societies need to recognize the impact they can have on promoting RCR and to expand their efforts in these three and other relevant areas. The examples provided demonstrate the components of a model for all scientific societies to follow in promoting RCR. PMID- 17726394 TI - Responding to challenges in educating for the responsible conduct of research. AB - The importance of responsible conduct of research (RCR) is widely recognized, but the necessary role for RCR education is limited by three significant challenges. First, the stated goals and purpose of RCR education are diverse, inconsistent, and sometimes not feasible. RCR is variably defined as knowing and following the rules, being a moral person, having good character, exhibiting good ethical judgment, and acting with integrity and responsibility. However, a case can be made that the long-term goals of RCR education can be reduced simply to decreasing research misconduct and increasing responsible conduct. A second challenge is that the methods for fostering RCR are unclear because the relationship between the goals and role of education has been unclear. To reconcile goals with feasible objectives, it is proposed that the focus of RCR education can be limited to three specific purposes: empowering trainees to respond to the ethical challenges raised in the conduct of research, increasing awareness of the purpose and value of ethical decision making as well as the roles and responsibilities of whistleblowers, and fostering a positive attitude about promoting an environment that values RCR. The third and final challenge is that a lack of dedicated financial support has decreased the likelihood that thoughtful, successful RCR programs can be developed. One means proposed to address the challenges of goals, methods, and strategies is a recently created national partnership, the RCR Education Committee (RCREC), a special interest group of the Association for Practical and Professional Ethics. PMID- 17726395 TI - On becoming a doctor: a patient teaches. PMID- 17726396 TI - Expanding responsible conduct of research instruction across the university. AB - During the past two decades, serious intellectual effort by governmental agencies, research institutions, professional societies, and educators has promoted education in the responsible conduct of research (RCR), defined present standards of RCR, and shaped the debate on how best to promote research integrity in the biomedical sciences. However, revisions to the Federal Policy on Research Misconduct in 2000 specifically expanded the policy's scope to include disciplines outside the biomedical and behavioral sciences, thus creating a need for RCR education in such fields as economics, education, mathematics, and linguistics. Even as some institutions have applied the Office of Research Integrity's (ORI) framework for RCR instruction university-wide, academic administrators and faculty from fields beyond the biomedical sciences have rightly noted that several of ORI's nine core instructional areas are tangential or irrelevant to the many disciplines whose research practices differ substantially from those of the biomedical sciences. These disciplines can benefit from the rich history of discourse, policy making, and education in RCR in the biomedical sciences, but they must not simply apply the standards of biomedical and behavioral science to their own, quite different research. Creative leadership from these newly included disciplines is needed to define standards of ethical research in their areas, prepare relevant educational materials, and promote a multidisciplinary perspective on research integrity across the university. The authors suggest that the scope of RCR education for federally funded research in other areas be addressed on two levels: (1) the content of generally applicable RCR education, and (2) the special, discipline specific content. PMID- 17726398 TI - Thomas Dover, M.B. (of Dover's Powder), physician and buccaneer. PMID- 17726400 TI - Physician assistant education in the United States. AB - As physician assistant (PA) programs developed in the 1960s, curriculum models emerged around the central themes of physician-dependent practice and competency based education. By 2007, there were 136 accredited programs in the United States, with 108 (79%) offering a master-degree curriculum. PA program preclinical and clinical curricula are typically evenly divided in length, and the typical U.S. PA program has a full-time attendance curriculum of 26.5 continuous months. In academic year 2005-2006, the typical PA student was a 27 year-old white woman with a 3.4 overall grade point average and 29 months of prior health care experience who matriculated with a baccalaureate degree into a master-degree PA program. In the 2005 application cycle, the number of applicants per available seat was 2.25 for both allopathic medical schools and PA programs. The transition to a predominately master-degree curriculum resulted in new challenges for PA faculty development, and the number of PA educators with terminal academic degrees continues to lag behind the educational needs of training programs. The topic of PA specialty training and recognition remains controversial. Although the PA profession has prospered since inception, concerns exist regarding workforce issues such as the appropriate balance of autonomy and supervision, role delineation, and the continuing trend toward specialization. The omission or inaccurate classification of PAs within U.S. health care access and workforce literature projects an incomplete picture, and it is important to consider the contributions PAs have made and will continue to make in addressing the nation's health care needs. PMID- 17726402 TI - The changing paradigm of contemporary U.S. allopathic medical school graduates' career paths: analysis of the 1997-2004 national AAMC Graduation Questionnaire database. AB - PURPOSE: During the last 15 years, the proportion of U.S. allopathic medical graduates planning to pursue alternative careers (other than full-time clinical practice) has been increasing. The authors sought to identify factors associated with contemporary medical graduates' career-setting plans. METHOD: The authors obtained anonymous data from the 108,408 U.S. allopathic medical graduates who completed the 1997-2004 national Association of American Medical Colleges Graduation Questionnaire (GQ). Using multinomial logistic regression, responses to eight GQ items regarding graduates' demographics, medical school characteristics, and specialty choice were tested in association with three career-setting plans (full-time university faculty; other, including government agencies, non-university-based research, or medical or health care administration; or undecided) compared with full-time (nonacademic) clinical practice. RESULTS: The sample included 94,101 (86.8% of 108,408) GQ respondents with complete data. From 1997 to 2004, the proportions of graduates planning full time clinical practice careers decreased from 51.3% to 46.5%; the proportions selecting primary care and obstetrics-gynecology specialties also decreased. Graduates reporting Hispanic race/ethnicity or no response to race/ethnicity, lower debt, dual advanced degrees at graduation, and psychiatric-specialty choice were consistently more likely to plan to pursue alternative careers. Graduates selecting an obstetrics-gynecology specialty/ subspecialty were consistently less likely to plan to pursue alternative careers. Being female, Asian/Pacific Islander, Black or Native American/Alaskan, and selecting non-primary-care specialties were variably associated with alternative career plans. CONCLUSIONS: As the medical student population becomes more demographically diverse, as graduates increasingly select non-primary-care specialties, and as dual-degree program graduates and alternative career opportunities for physicians expand, the proportion of U.S. graduates planning full-time clinical practice careers likely will continue to decline. PMID- 17726403 TI - A three-year accelerated medical school curriculum designed to encourage and facilitate primary care careers. AB - For the past decade there has been declining medical student interest in primary care. The cause of this trend is multifactorial and includes issues of salary and indebtedness. Educational leaders have called for careful selection of medical students and the creation of three-year medical school curricula to counter these factors. On April 30, 2006, the American Osteopathic Association Commission on College Accreditation voted to approve a new accelerated curriculum at the Lake Erie College of Osteopathic Medicine (LECOM) in Erie, Pennsylvania. This pathway accelerates the traditional four-year medical school curriculum into three calendar years. In addition to reducing the time necessary to complete medical training as a primary care physician, this pathway reduces the expense involved in obtaining a medical education. This paper describes how LECOM positioned itself to address key strategies believed to be at the heart of rekindling student interest in primary care. In the accelerated curriculum, summer vacation between the first and second medical school year is eliminated. Clinical education is streamlined by focusing on 16 rotations relevant to primary care and eliminating elective experiences. Primary care mentors are assigned at the start of medical school. Case-based capstone sessions are added throughout the clinical years to reinforce primary care concepts. Students in this curriculum are designated "primary care scholars" to recognize the fact that they are engaged in a rigorous, goal-directed curriculum. Consistent with published recommendations for increasing medical students' choice of generalist careers, a detailed description of the LECOM accelerated curriculum effort is provided. PMID- 17726404 TI - Viewpoint: developing a research ethics consultation service to foster responsive and responsible clinical research. AB - Although clinical ethics has become a central, and welcome, component of the health care landscape, research ethics consultation services are still uncommon. Indeed, the usual approach to ethical concerns in research with human subjects has been primarily a regulatory one. Nonetheless, ethical problems also arise in the context of research and thus collaborations between investigators and research ethicists are as essential as those between physicians and clinical ethicists. The authors argue that the use of research ethics consultation services can be of benefit to clinical scientists, bioethicists, research institutions, and research subjects. Such services can increase sensitivity among researchers to the ethical implications of their work, result in better institutional research policies, and facilitate the development of an organizational culture that is receptive to the identification and resolution of ethical conflicts. The authors conclude by describing the process of development and implementation of such a research ethics consultation service at Weill Medical College of Cornell University. PMID- 17726405 TI - Difficult conversations in health care: cultivating relational learning to address the hidden curriculum. AB - The authors describe the philosophy and pedagogical approach of an innovative educational program, grounded in principles of relational learning and designed to improve the preparedness of health care professionals for engaging in challenging conversations with patients and families. The Program to Enhance Relational and Communication Skills (PERCS) is a project of The Institute for Professionalism and Ethical Practice at Children's Hospital Boston, developed in collaboration with Education Development Center, Inc. The one-day workshop is interdisciplinary in its structure, includes practitioners with varying levels of professional experience, uses trained actors to portray patients and family members, and involves learners in improvised case scenarios. The program responds to several developments in contemporary health care: medical education reform, changing definitions of professional competence, and calls for greater attention to qualities of compassion, trust, and respect in practitioners' relationships with patients and families. The program's pedagogy responds to these developments by creating a safe climate for relational learning, by enacting emotionally challenging and ethically salient case scenarios, and by integrating patient and family perspectives in novel and substantive ways. By creating a curriculum and learning environment that explicitly embraces the moral experience of learners, the program's developers aim to exert a countercultural influence on the dehumanizing effects of the hidden curriculum. PMID- 17726406 TI - European guidelines on cardiovascular disease prevention in clinical practice: executive summary. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts). PMID- 17726409 TI - Randomized trial of single-dose intramuscular dexamethasone compared with prednisolone for children with acute asthma. AB - OBJECTIVES: To compare the clinical efficacy of single-dose intramuscular (IM) dexamethasone phosphate to a 5-day course of oral prednisolone for the treatment of moderate asthma exacerbations in young children discharged from the emergency department (ED). METHODS: We performed a prospective, randomized trial in children aged 18 months to less than 7 years with asthma who presented to the ED with a clinical asthma score of 3 to 7 on a 9-point scale. Children were randomized to 1 dose of IM dexamethasone (0.6 mg/kg, maximum 15 mg) or oral prednisolone (2 mg/kg, maximum 50 mg) once daily for 5 days. The primary outcome, measured only for patients discharged from the ED, was change in asthma score from ED presentation to 4-day follow-up examination, as assessed by a physician masked to group assignment. We assessed secondary clinical course outcomes by a structured interview at 4 and 14 days. RESULTS: Eighty-eight patients were appropriately randomized to dexamethasone and 93 to prednisolone. Group characteristics were similar at baseline. Among those discharged from the ED, 62 (90%) of 69 and 64 (90%) of 74 patients in the dexamethasone and prednisolone groups, respectively, were reassessed at 4 days for the primary outcome. The mean change in total asthma score at 4-day follow-up was 3.6 in the dexamethasone group and 3.4 in the prednisolone group (difference, 0.2; 95% confidence interval, -0.4 to 0.7). Of patients initially discharged, 5.9% of dexamethasone patients and 4.1% of prednisolone patients were admitted before the 2-week follow up (difference, 1.8%; 95% confidence interval, -5.4% to 9.0%). CONCLUSIONS: A single dose of IM dexamethasone showed no clinically meaningful difference in outcomes compared with a 5-day course of oral prednisolone for the treatment of moderate acute asthma exacerbations in young children who are discharged from the ED. PMID- 17726407 TI - European guidelines on cardiovascular disease prevention in clinical practice: full text. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts). PMID- 17726410 TI - Diagnosis and guided reduction of forearm fractures in children using bedside ultrasound. AB - BACKGROUND: Forearm fractures are common injuries in children. Displaced and angulated fractures usually require reduction. Ultrasound diagnosis and guided reduction offer several potential advantages: (1) the procedure does not involve ionizing radiation; (2) compared with fluoroscopy units, the newer ultrasound units are more portable; and (3) repeated studies can be obtained easily and quickly. OBJECTIVE: The primary objective was to investigate the accuracy of emergency department (ED) physician-performed ultrasound in the diagnosis and guided reduction of forearm fractures in children. METHODS: Children suspected of having forearm fractures were enrolled prospectively in an urban pediatric ED from June 2004 to November 2004. A bedside ultrasound of the forearm bones was performed by a pediatric emergency medicine physician. Ultrasound findings were compared with radiograph findings. Reductions were performed under ultrasound guidance. Postreduction radiographs were performed. Any need for further reduction was recorded. RESULTS: During the study period, 68 patients were enrolled. Radiographs revealed forearm fractures in 48 patients. Twenty-nine subjects had fractures of the radius alone; 17 had fractures of both the radius and the ulna, and 2 had fractures of the ulna alone. Ultrasound revealed the correct type and location of the fracture in 46 patients. The sensitivity for the detection of forearm fractures was 97% (95% confidence interval [CI], 89%-100%) using ultrasound. The specificity was 100% (95% CI, 83%-100%). Twenty-six subjects underwent reduction of their fractures in the ED. Two subjects required rereduction after the initial reduction. The initial success rate of ultrasound guided reduction was 92% (95% CI, 75%-99%). CONCLUSIONS: Bedside ultrasound performed by pediatric emergency medicine physicians is a reliable and convenient method of diagnosing forearm fractures in children. It is also useful in guiding the reduction of these fractures. PMID- 17726411 TI - Appropriateness of children's nonurgent visits to selected Michigan emergency departments. AB - OBJECTIVES: To explore parental rationale and the appropriateness of children's visits to emergency departments (EDs) for nonurgent complaints. METHODS: At 13 Michigan EDs, interviews were conducted with parents of children aged 6 months to 18 years who were triaged by ED personnel as lowest acuity. Interviews explored chief complaint, reason for ED visit, insurance status, attempts to call for advice before coming to the ED, and usual primary care source. Investigators rated ED visit appropriateness as high, medium, or low based on characteristics of the complaint and parent care-seeking behaviors. RESULTS: Of 422 completed interviews, 51% involved parents of Medicaid enrollees, and 43% involved parents of privately insured enrollees. One third of children presented with injuries. Overall, 50% of visits were rated as high appropriateness. When injuries were excluded, 37% of visits were rated as high appropriateness. Thirty-eight percent of parents called for advice before coming to the ED; of those, 60% were told to go to the ED. The most common parent-reported reason for going to the ED was reassurance (41%), followed by thinking the situation was an emergency (33%). Medicaid patients who could name a primary care physician, rather than a clinic only, were more likely to have ED visits rated as high appropriateness (54% vs 38%, P < 0.05). CONCLUSIONS: Half of all nonurgent ED visits were rated as high appropriateness. Considering parental information sources, it would be incorrect to label all nonurgent ED visits as inappropriate. Questions remain as to whether primary care outpatient sites are an appropriate source of care for minor injuries. PMID- 17726412 TI - Lack of evidence to support routine digital rectal examination in pediatric trauma patients. AB - BACKGROUND: Current advanced trauma life support guidelines recommend that a digital rectal examination (DRE) should be performed as part of the initial evaluation of all trauma patients. Our primary goal was to estimate the test characteristics of the DRE in pediatric patients for the following injuries: (1) spinal cord injuries, (2) bowel injuries, (3) rectal injuries, (4) pelvic fractures, and (5) urethral disruptions. METHODS: We conducted a nonconcurrent, observational, chart review study of a consecutive series of pediatric trauma patients. We enrolled all patients younger than 18 years seen in our ED from January 2003 to February 2005, for whom the trauma team was activated and who had a documented DRE. For each patient, we reviewed all available clinical documents in a computerized medical record system to identify the DRE findings followed by review of radiological reports, operative reports, and discharge summaries to identify specific injuries. RESULTS: Two hundred thirteen patients met our selection criteria and were included in the analysis. We identified 3 patients with spinal cord injury (1% prevalence), 13 patients with bowel injury (6%), 5 patients with rectal injury (2%), 12 patients with a pelvic fracture (6%), and 1 patient with urethral disruption (0.5%). The DRE failed to diagnose (false negative rate) 66% of spinal cord injuries, 100% of bowel injuries, 100% of rectal wall injuries, 100% of pelvic fractures, and 100% of urethral disruption injuries. CONCLUSIONS: The DRE has poor sensitivity for the diagnosis of spinal cord, bowel, rectal, bony pelvis, and urethral injuries. Our findings suggest that the DRE should not be routinely used in pediatric trauma patients. PMID- 17726413 TI - A randomized clinical trial of oral transmucosal fentanyl citrate versus intravenous morphine sulfate for initial control of pain in children with extremity injuries. AB - BACKGROUND: Extremity injury is a common condition that requires pain management in an emergency department. In pediatric patients, the most frequently used method of pain control is intravenous (IV) morphine sulfate. Oral transmucosal fentanyl citrate (OTFC) is a potential alternative to morphine, which may obviate the need to place an IV before addressing pain. OBJECTIVE: To compare OTFC with IV morphine for sedation and analgesia during initial evaluation of children with deformity of an extremity and suspected fracture. DESIGN/METHODS: A randomized controlled trial of OTFC versus IV morphine in which 8- to 18-year-olds presenting to pediatric tertiary care emergency department with extremity deformity and suspected fracture were eligible. Only those with visual analog scale (VAS) (0 = no pain, 100 = worst pain imaginable) score equal to or greater than 50/100, and American Society of Anesthesia I or II qualified. Patients were excluded if history of loss of/altered level of consciousness, multiple traumatic injuries, or if patient had received prior medication for pain control. All patients enrolled were randomly assigned to receive either IV morphine (0.1 mg/kg) or OTFC (10-15 mug/kg). Patients rated pain intensity using VAS; scores were recorded before medicating and at 15-minute intervals after the medication was given. Adverse events such as emesis, pruritus, and respiratory depression were recorded. RESULTS: A total of 87 patients were enrolled in study (OTFC, 47; morphine, 40). There are no significant differences between the 2 groups when comparing sex, age, weight, and pretreatment VAS score (P > 0.05). Although the VAS scores were not significantly different before medicating the patient, an analysis of variance shows that there was a significant difference (P > 0.05) in VAS scores at 30 minutes. The differences persisted for every 15 minutes through the 75 minutes of monitoring. There was no statistically significant difference between the 2 groups when comparing the number of adverse events (P = 0.23). CONCLUSIONS: The use of OTFC can provide improved pain control when compared with IV morphine. The pain reduction starts 30 minutes after initiation of medication, and the effect is seen as far as 75 minutes after the initiation of analgesic medication. The study size was too small to make any statements concerning adverse effects; thus, further studies with larger sample sizes are needed to determine the use of OTFC. PMID- 17726414 TI - Test characteristics of parent's visual analog scale score in predicting ventriculoperitoneal shunt malfunction in the pediatric emergency department. AB - OBJECTIVES: Many parents of children with ventriculoperitoneal shunts present to the emergency department for evaluation of a possible shunt malfunction. No study to date has evaluated their ability to predict a shunt malfunction. Our study objective was to evaluate parents' accuracy for predicting a shunt malfunction in their child. We hypothesize that parents more experienced with prior shunt malfunctions are better able to predict subsequent malfunctions in their child. METHODS: We conducted a prospective, descriptive study on children younger than 18 years presenting to our tertiary care pediatric emergency department with a possible ventriculoperitoneal shunt malfunction. Parents rated the likelihood of a shunt malfunction using an unmarked 100-mm visual analog scale marked definitely malfunctioning at the high end. An experienced parent was defined as one who had previously experienced at least 3 shunt malfunctions in their child. RESULTS: We enrolled 85 parent-child dyads in our study. Twenty-four children were diagnosed with a malfunction. The predictive ability of parents to determine a shunt malfunction was found at a threshold visual analog scale score of 66 (sensitivity, 88.9%, and specificity, 62.2%). At a determined threshold value of 85 or more, experienced parents had a high specificity of 89.2% with a positive likelihood ratio of 5.1. Experienced parents showed an area under the curve of 0.7928 (95% confidence interval, 0.6037-0.9819); and inexperienced parents, 0.5611 (95% confidence interval, 0.3646-0.7576) (P = 0.096). CONCLUSIONS: Experienced parents are better able to predict a shunt malfunction in their child. PMID- 17726416 TI - The use of an emergency physician-directed bedside ultrasound examination to clarify a diagnosis in an 8-year-old boy with chronic abdominal pain. AB - Abdominal pain is a common presenting complaint to the emergency department. Often, patients with chronic, intermittent histories of abdominal pain with multiple visits to medical providers find it difficult to be taken seriously. We describe a patient with a history of episodic abdominal pain who was found to have intermittent ureteropelvic junction obstruction after a timely ultrasound examination by the treating emergency physician. PMID- 17726415 TI - Characterizing the teachable moment: is an emergency department visit a teachable moment for intervention among assault-injured youth and their parents? AB - OBJECTIVES: Injury interventions often invoke the teachable moment (TM); however, there is scant empirical research examining this construct with violent injuries. We sought to operationalize the TM construct and to determine whether an emergency department (ED) visit was a TM for intervention among assault-injured adolescents and their parents. SETTING AND PARTICIPANTS: One hundred sixty-eight youth (age, 10-15 years) and their parents presenting to the ED with interpersonal assault injuries at 2 urban medical centers. METHODS AND ANALYSIS: Data were collected using ED record abstraction and interviews. Interview questions assessed perceived injury severity, perceived susceptibility, and preventability/ability to avoid future conflict. Data were examined by age, sex, weapon involvement, and time elapsed between injury and interview. Factor analysis was used to identify the components of the TM construct, and a TM index was created for youth and parents. RESULTS: Youth and parents found their trip to the ED moderately stressful, although parents perceived more stress than youth. Older youth (13-15 years old) and the parents of younger youth (10-12 years old) were most likely to see their injuries as preventable. The parent TM index was positively correlated with parent-reported aggression (r = 0.16, P < 0.03); the youth's TM index scores were associated with the time elapsed since the event (r = -0.16, P = 0.03). CONCLUSIONS: This study provides preliminary support for the TM after assault injuries. The TM index may be a first step toward an assessment that can differentiate individuals who are amenable to violence prevention intervention from those who are not. PMID- 17726417 TI - Tension pneumoperitoneum after intussusception pneumoreduction. AB - Intussusception is the most common cause of intestinal obstruction in infancy. Presentation, diagnostic workup, and treatment are well understood and noncontroversial. Complications of bowel perforation are also well documented. We discuss a case of tension pneumoperitoneum after intestinal perforation during intussusception pneumoreduction in a 5-month-old child and review initial presentation, diagnosis, and management of this disease. It is important to recognize this rare complication of pneumoreduction and promptly treat the ensuing tension pneumoperitoneum. PMID- 17726418 TI - A neonate with respiratory distress and a chest wall deformity. AB - Infants with respiratory distress commonly present to a pediatric emergency department. There are rare but serious conditions that need to be considered in the differential diagnosis. We report the history of an infant that presented to our institution with respiratory distress ultimately diagnosed with a mesenchymal hamartoma of the chest wall. The presentation, diagnosis, and treatment options for mesenchymal hamartoma are discussed. PMID- 17726419 TI - Severe hypermagnesemia as a result of excessive cathartic ingestion in a child without renal failure. AB - A 14-year-old girl was referred to our hospital with lethargy and hypotension and was found to have a serum magnesium level of 14.9 mg/dL after having received an magnesium hydroxide (Magnesie Calcinee) for 7 days because of constipation. She was lethargic, her blood pressure was 70/40 mm Hg, and electrocardiogram revealed prolonged corrected QT interval and first-degree atrioventricular block. She has no renal dysfunction. Emergency hemodialysis after her condition ameliorated, her serum magnesium levels returned to normal. The present case suggests that massive oral magnesium ingestion with severe constipation and ileus may result severe hypermagnesemia without renal dysfunction. PMID- 17726420 TI - A 16-year-old boy with acute urinary retention. AB - Urinary retention can be described as the inability to void volitionally despite an adequate volume of urine in the bladder. It is a common complaint in adults, especially among elderly males with benign prostatic hyperplasia. Children, in contrast, are more likely to have voluntary retention of urine due to urethral irritation or dysuria. Gently massaging the suprapubic region while the child is in a warm bath often relieves the retention in these cases. Other patients described as lazy voiders can present with acute urinary retention. These patients are typically young girls who are embarrassed to void at school. Retraining or timed voiding is often successful managing lazy voiders. However, these benign disorders should only be diagnosed after anatomical or organic causes for their symptoms have been considered and ruled out. PMID- 17726421 TI - Case report of precursor B-cell lymphoblastic lymphoma presenting as syncope and cardiac mass in a nonimmunocompromised child. AB - We report the case of a previously healthy, 10-year-old boy who presented to the emergency department with a syncopal episode. In the emergency department, the patient was diagnosed with a right atrial mass, later identified as a precursor B cell lymphoblastic lymphoma (LL). Most causes of syncope in children are not life threatening. In most cases, it indicates a predisposition to vasovagal episodes. Lymphomas account for approximately 7% of malignancies among children younger than 20 years, are more common in white males and immunocompromised patients, and are predominantly tumors of T-cell origin. Children with non-Hodgkin lymphoma usually present with extranodal disease, most frequently involving the abdomen (31%), mediastinum (26%), or head and neck (29%). Our patient was unique in that he was a nonimmunocompromised, black boy, presenting with syncope in the setting of a large atrial mass identified as a precursor B-cell LL. To our knowledge, there are no reported cases of precursor B-cell LL presenting as syncope and a cardiac mass. PMID- 17726422 TI - Controversies in the sequelae of pediatric mild traumatic brain injury. AB - Traumatic brain injury is a common occurrence in the pediatric population, and the majority of injuries are considered to be mild. There are varying definitions of mild traumatic brain injury. Classification systems for injury severity may include initial Glasgow Coma Scale, duration of loss of consciousness, and duration of posttraumatic amnesia. Postconcussion syndrome is a constellation of symptoms, which may develop after traumatic brain injury. The symptoms can occur in the areas of cognitive, somatic, and/or affective/emotional complaints. There continues to be controversy concerning the definition of mild traumatic brain injury, the significance of postconcussion syndrome, and the development of other posttraumatic neuropsychological changes. This article will review the literature on the sequelae of pediatric mild brain injury and discuss areas of controversy. PMID- 17726424 TI - Evidence-based guidelines for family presence in the resuscitation room: a step by-step approach. AB - The benefits of family presence (FP) during resuscitation have been well documented in the literature for the past 20 years. However, many hospitals lack written guidelines to direct staff members during a resuscitation event. A structured approach affords staff a uniform and organized way to offering FP, avoiding any interference with patient care. The purpose of this paper is to provide evidence-based practice guidelines to offering FP during resuscitation in the emergency department. The guidelines illustrate a practical step-by-step approach that staff members can follow every time a patient is being evaluated and/or treated in the resuscitation room. PMID- 17726425 TI - ECGs in the ED. PMID- 17726426 TI - Pediatric emergency medicine: legal briefs. PMID- 17726427 TI - Pediatric Residency Training Program at the University of Alberta. PMID- 17726428 TI - How to assess low back pain. PMID- 17726429 TI - Do high levels of IgA rheumatoid factor indicate a poor response to treatment with TNF inhibitors in patients with RA? PMID- 17726430 TI - Should patients with prostate cancer without bone metastases receive sodium clodronate? PMID- 17726431 TI - Prospective, randomized, double-blind trial shows aerobic exercise is a valid treatment option for chronic prostatitis. PMID- 17726432 TI - Detection of occult lymph node metastases in locally advanced node-negative prostate cancer. PMID- 17726433 TI - Hypertrophy and hyperplasia of abdominal adipose tissues in women. AB - OBJECTIVE: To examine the expression of selected transcription factors involved in adipogenesis and genes related to lipid metabolism in abdominal subcutaneous and omental fat tissue. RESEARCH DESIGN AND METHODS: We obtained subcutaneous and omental adipose tissue samples from 40 women undergoing abdominal hysterectomies (age: 47+/-5 years; BMI 27.9+/-5.3 kg/m(2)). We measured isolated adipocyte size and metabolism, and detailed measures of body fat accumulation and body fat distribution were obtained (dual-energy X-ray absorptiometry and computed tomography, respectively). RESULTS: Adipocyte size of both subcutaneous and omental fat were increased with higher body fat mass values, with similar regression slopes in each compartment. In contrast, with higher body fat mass values, fat accumulation was progressively higher in the subcutaneous than in the visceral fat compartment, suggesting hyperplasia in the subcutaneous fat compartment. Messenger RNA levels of CEBPalpha, PPARgamma2, SREBP1c and genes related to lipid metabolism (LPL, FABP4, DGAT1, DGAT2, PLIN and HSL) were significantly higher in subcutaneous than in omental fat tissue (P< or =0.001 for all). Only subcutaneous expression of these genes tracked with obesity levels as reflected by significant positive associations between subcutaneous fat CEBPalpha, SREBP1c and DGAT2 expression and total body fat mass (r=0.37, r=0.41, r=0.57, respectively, P< or =0,05), fat percentage (r=0.40, r=0.39, r=058, respectively, P< or =0,05) and subcutaneous adipose tissue area (r=0.36, r=0.38, r=0.58, respectively, P< or =0,05). Omental adipose tissue expression levels of these genes were not significantly related to adiposity measures. CONCLUSIONS: These results show that in obese women, hyperplasia is predominant in the subcutaneous fat depot, whereas fat cell hypertrophy is observed both in the omental and subcutaneous compartments. PMID- 17726434 TI - The biology of behaviour: scientific and ethical implications. PMID- 17726435 TI - How to house a mind inside a brain. Lessons from history. PMID- 17726436 TI - Understanding the brain. How can our intuition fail so fundamentally when it comes to studying the organ to which it owes its existence? PMID- 17726437 TI - Clock genes running amok. Clock genes and their role in drug addiction and depression. PMID- 17726438 TI - Linking emotion to the social brain. The role of the serotonin transporter in human social behaviour. PMID- 17726439 TI - Beyond susceptibility. Behavioural genetics can advance our understanding of psychiatric disorders, but might not meet the expectations for new cures. PMID- 17726440 TI - The emergence of genomic psychology. Insights from genomic analyses might allow psychologists to understand, predict and modify human behaviour. PMID- 17726441 TI - Capacity and competence in children as research participants. Researchers have been reluctant to include children in health research on the basis of potentially naive assumptions. PMID- 17726442 TI - Thinking inside the box. To cope with an increasing disease burden, drug discovery needs biologically relevant and predictive testing systems. PMID- 17726443 TI - Trust in the brain. Neurobiological determinants of human social behaviour. PMID- 17726444 TI - Towards a philosophy for neuroethics. An informed materialist view of the brain might help to develop theoretical frameworks for applied neuroethics. PMID- 17726445 TI - Neuroethics beyond genethics. Despite the overlap between the ethics of neuroscience and genetics, there are important areas where the two diverge. PMID- 17726446 TI - Empirical neuroethics. Can brain imaging visualize human thought? Why is neuroethics interested in such a possibility? PMID- 17726447 TI - Does it make sense to speak of neuroethics? Three problems with keying ethics to hot new science and technology. PMID- 17726448 TI - Who will guard the guardians of neuroscience? Firing the neuroethical imagination. PMID- 17726449 TI - From DNA to mind. The decline of causality as a general rule for living matter. PMID- 17726450 TI - The impact of FDA and EMEA guidelines on drug development in relation to Phase 0 trials. AB - An increase in the number of identified therapeutic cancer targets achieved through recent biomedical research has resulted in the generation of a large number of molecules that need to be tested further. Current development of (anticancer) drugs is a rather inefficient process that for an average new molecule takes around 10-15 years. It is also a challenging process as it is associated with high costs and a low rate of approval. It is known that less than 10% of new molecular entities entering clinical Phase I testing progress beyond the investigational programme and reach the market; this probability is even lower for anticancer agents. In 2003, the US Food and Drug Administration (US FDA) declared the urgent need for new toolkits to improve the critical development path that leads from scientific discovery to the patient. In this scenario, Phase 0 (zero) trials should allow an early evaluation in humans of pharmacokinetic and pharmacodynamic profiles of test compounds through administration of sub-pharmacological doses and for a short time period to a low number of humans. Typically, Phase 0 studies have no therapeutic or diagnostic intent. Owing to the low doses administered and the low risk of toxicity, shorter preclinical packages to support these studies are required. Phase 0 trials have been proposed to help in making an early selection of promising candidates for further evaluation in Phase I-III trials, providing a potentially useful instrument for drug discovery, particularly in the field of oncology. Phase 0 studies are expected to reduce costs of drug development, and to limit the preclinical in vitro and in vivo testing and the time period of drug development. However, there are also concerns about the utility and feasibility of Phase 0 studies. In January 2006, guidelines on exploratory investigational new drug studies in humans have been published by the US FDA, and currently a Phase 0 programme is ongoing at the National Cancer Institute to evaluate the impact (feasibility and utility) of Phase 0 studies on drug development. In Europe, a Position Paper produced by the Evaluation of Medicinal Products (EMEA) in 2004 raised the possibility of a reduced preclinical safety package to support early microdose clinical studies, and, as announced by a recent Concept Paper on medicinal products published by the committee for medicinal products for human use of the EMEA, EMEA's guidelines on Phase 0 studies are expected shortly. The true impact of Phase 0 studies on the drug development process as well as on the safety needs to be carefully explored. PMID- 17726451 TI - Optimal indications of endocrine therapy alone as adjuvant systemic treatment of breast cancer. AB - We examined the validity of the St Gallen algorithm for Japanese breast cancer patients and sought the optimal indications of endocrine monotherapy as adjuvant systemic treatment. According to the 2005 St Gallen algorithm, endocrine responsiveness (responsive, uncertain, or non-responsive) and recurrence risk (low, intermediate, or high) were assessed in 436 invasive breast cancer patients, who underwent surgery and adjuvant therapy of tamoxifen alone in 1982 1993. Furthermore, intermediate-risk patients were divided into three groups based on lymph node metastasis and number of risk factors as follows: Group A, negative lymph node metastasis and one risk factor; Group B, negative lymph node metastasis and two to five risk factors; and Group C, positive lymph node metastasis. Cumulative 10-year recurrence-free survival (RFS) rates of each type were calculated. Recurrence-free survival was as follows: endocrine responsiveness; responsive: 86.0%, uncertain: 79.5%, non-responsive: 72.4%, risk category; low: 93.3%, intermediate: 84.0%, high: 59.6%, intermediate-risk patients; Group A: 93.5%, Group B: 88.2%, and Group C: 75.0%. In conclusion, patient classification based on St Gallen algorithm appears valid in Japanese breast cancer patients. Endocrine monotherapy may be sufficient as adjuvant treatment in the intermediate-risk patients, in which only one risk factor was present without any metastatic involvement in lymph node. PMID- 17726452 TI - Combining gene and immunotherapy for prostate cancer. AB - The nitroreductase (NR)/CB1954 enzyme prodrug system has given promising results in pre-clinical studies and is currently being assessed in phase I and II clinical trials in prostate cancer. Enhanced cell killing by apparent immune mediated mechanisms has been shown in pancreatic and colorectal cancer models, by co-expressing murine granulocyte macrophage colony-stimulating factor (GM-CSF) with NR in a single replication deficient adenoviral vector. This consists of the CMV immediate early promotor driving expression of NR, with an internal ribosome entry site (IRES) and the gene for murine GM-CSF (mGM-CSF). To examine if similar enhancement of tumour cell killing could be produced in prostate cancer, the TRAMP model was chosen. Results illustrate that the combination of suicide gene therapy using NR and CB1954, with cytokine stimulation with mGM-CSF gives an improved response compared with either modality alone. The mechanism of this improved response is however likely to be non-immune based as it lacks a memory effect. PMID- 17726453 TI - Allelic variation in ApoC3, ApoA5 and LPL genes and first and second generation antipsychotic effects on serum lipids in patients with schizophrenia. AB - Schizophrenic patients who are treated with antipsychotics, especially second generation antipsychotics, such as clozapine and olanzapine, manifest an increase in cholesterol and triglycerides as well as other changes associated with diabetes or the metabolic syndrome. Previous studies have shown that polymorphisms in several genes that regulate lipid metabolism can influence the levels of these lipids and response to drug treatment. We have investigated in an exploratory study whether polymorphisms in the apolipoprotein C-III (ApoC3), apolipoprotein A-V gene (ApoA5) and lipoprotein lipase genes influence differential lipid response to treatment with three second generation antipsychotics-olanzapine, clozapine and risperidone-or treatment with a first generation antipsychotic. A total of 189 patients with schizophrenia or schizoaffective disorder who were being treated with a single antipsychotic were studied in a cross-sectional study design in which fasting serum cholesterol and triglycerides and selected single-nucleotide polymorphosms (SNPs) in the three lipid metabolism genes were assessed. The treatment with antipsychotic monotherapy makes drug haplotype ascertainment less complex. Our analyses showed several nominally significant drug x gene and drug x haplotype interactions. The rarer C allele or the ApoA5_1131 (T/C) SNP was associated with higher cholesterol levels in patients treated with first generation antipsychotics and lower cholesterol levels in patients treated with olanzapine or clozapine. The rarer C allele of the ApoA5_SW19 (G/C) SNP was associated with higher cholesterol in risperidone-treated patients. An ApoA5 CG haplotype was associated with decreased cholesterol in olanzapine- or clozapine-treated patients and higher cholesterol in patients treated with first generation antipsychotics. The presence of the rarer T allele of the ApoC3_1100 (C/T) SNP or the presence of the ApoC3 TG haplotype was associated with decreased triglyceride levels in patients treated with olanzapine or clozapine and a nonsignificant trend for increased triglycerides in patients treated with first generation antipsychotics. The presence of the ApoC3 CC haplotype was associated with increased triglycerides in patients treated with olanzapine or clozapine. The overall magnitude of the effects was not large. These results provide a potential initial step toward a pharmacogenetic approach to selection of antipsychotic treatment which may help minimize the side effect of increases in serum lipids. PMID- 17726454 TI - Expression of long anti-HIV-1 hairpin RNAs for the generation of multiple siRNAs: advantages and limitations. AB - Promoter expressed long-hairpin RNAs (lhRNAs) that can be processed into multiple small interfering RNA (siRNAs) are being considered as effective agents for treating rapidly mutating viruses such as human immunodeficiency virus (HIV). In the present study, we have generated human U6 promoter-driven lhRNAs of 50, 53, and 80 base pairs (bp) targeting contiguous sequences within the tat and rev genes of HIV-1 and evaluated the efficacy of these lhRNAs as well as their processing in cells. By using multiple G:U mismatches in the stems, we have been able to readily incorporate the long-hairpin structures into a lentiviral vector transduction system. Here we show that such long hairpins can be stably and functionally expressed for a long term in HIV-1 susceptible T cells, where they provide potent inhibition of HIV replication against both non-mutant and mutant variants of HIV-1. Our studies provide strong support for the use of the G:U wobble pair containing lhRNAs to generate multiple siRNAs from a single transcript, but we also show that lhRNAs of 80 bp may be the upper size limit for effectively producing multiple, functional siRNAs. PMID- 17726455 TI - New insights and unresolved issues regarding insertional mutagenesis in X-linked SCID gene therapy. AB - The oncogenic potential of retrovirus-mediated gene therapy has been re emphasized because four patients developed T-cell acute lymphoblastic leukemia (T ALL)-like disease from an otherwise successful gene therapy trial for X-linked severe combined immunodeficiency (X-linked SCID). X-linked SCID, a disease caused by inactivating mutations in the IL2Rgamma gene, is part of a heterogeneous group of SCIDs characterized by the lack of T cells in conjunction with the absence of B and/or natural killer (NK) cells. Gene therapy approaches are being developed for this group of diseases. In this review we discuss the various forms of SCID in relation to normal T-cell development. In addition, we consider the possible role of LMO2 and other T-ALL oncogenes in the development of adverse effects as seen in the X-linked SCID gene therapy trial. Furthermore, we debate whether the integration near the LMO2 locus is sufficient to result in T-ALL-like proliferations or whether the gamma-retroviral viral expression of the therapeutic IL2RG gene contributes to leukemogenesis. Finally, we review some newly developed murine models that may have added value for gene therapy safety studies. PMID- 17726456 TI - Prevention of irradiation-induced salivary hypofunction by microvessel protection in mouse salivary glands. AB - Treatment of most head and neck cancers includes radiotherapy. Salivary glands (SGs) in the irradiation (IR) field are irreversibly damaged resulting in severe hyposalivation. We evaluated the importance of SG endothelial cells to this IR induced injury, and whether serotype 5 adenoviral (Ad5) vector-mediated transfer of basic fibroblast growth factor (AdbFGF) or vascular endothelial growth factor (AdVEGF) complementary DNAs would afford radioprotection. Four hours after IR, microvessel density (MVD) in SGs decreased by approximately 45%. However, if mice were pre-treated with either AdVEGF or AdbFGF 48 hours before IR the loss in MVD was significantly reduced. An irrelevant vector, AdLacZ, encoding Escherichia coli beta-galactosidase, was without effect. After 8 weeks, IR reduced salivary flow by approximately 65% in untreated mice. Mice pre-treated (using 5 x 10(9) particles/gland 48 hours prior to IR) with AdLacZ exhibited a reduction in salivary flow similar to untreated mice receiving IR. However, irradiated mice pre-treated with AdbFGF or AdVEGF showed a significant improvement in their salivary flow, to approximately 70% (P < 0.01) and 80% (P < 0.01), respectively, compared to non-irradiated control mice. These results are consistent with the notion that injury to the adjacent microvasculature may play an important role in SG radiation damage. Furthermore, our results suggest that a local transient treatment directed at protecting SG endothelial cells may be beneficial for patients undergoing IR for head and neck cancer. PMID- 17726457 TI - Autologous transplantation of SM/C-2.6(+) satellite cells transduced with micro dystrophin CS1 cDNA by lentiviral vector into mdx mice. AB - Duchenne muscular dystrophy (DMD) is a lethal muscle disorder caused by mutations in the dystrophin gene. Transplantation of autologous myogenic cells genetically corrected ex vivo is a possible treatment for this disorder. In order to test the regenerative efficiency of freshly isolated satellite cells, we purified quiescent satellite cells from limb muscles of 8-12-week-old green fluorescent protein-transgenic (GFP-Tg) mice using SM/C-2.6 (a recently developed monoclonal antibody) and flow cytometry. Freshly isolated satellite cells were shown to participate in muscle regeneration more efficiently than satellite cell-derived myoblasts passaged in vitro do, when transplanted into tibialis anterior (TA) muscles of 8-12-week-old cardiotoxin-injected C57BL/6 mice and 5-week-old dystrophin-deficient mdx mice, and analyzed at 4 weeks after injection. Importantly, expansion of freshly isolated satellite cells in vitro without passaging had no detrimental effects on their regenerative capacity. Therefore we directly isolated satellite cells from 5-week-old mdx mice using SM/C-2.6 antibody and cultured them with lentiviral vectors expressing micro-dystrophin CS1. The transduced cells were injected into TA muscles of 5-week-old mdx mice. At 4 weeks after transplantation, the grafted cells efficiently contributed to regeneration of mdx dystrophic muscles and expressed micro-dystrophin at the sarcolemma. These results suggest that there is potential for lentiviral vector mediated ex vivo gene therapy for DMD. PMID- 17726458 TI - Inhibition of tumor growth and metastasis establishment by adenovirus-mediated gene transfer delivery of the antiangiogenic factor 16K hPRL. AB - Tumor metastases, the most fearsome aspect of cancer, are generally resistant to conventional therapies. Angiogenesis is a crucial aspect of tumor growth and metastatic dissemination. Antiangiogenic therapy, therefore, holds potential as an attractive strategy for inhibiting metastasis development. Human 16K PRL (16K hPRL), a potent inhibitor of angiogenesis, has been demonstrated to prevent tumor growth in two xenograft mouse models, but whether it also affects tumor metastasis is unknown. In this study we will investigate the ability of 16K hPRL to prevent the establishment of metastasis. We demonstrate that 16K hPRL administered via adenovirus-mediated gene transfer, inhibits tumor growth by 86% in a subcutaneous (SC) B16-F10 mouse melanoma model. Computer-assisted image analysis shows that 16K hPRL treatment results in a reduction of tumor-vessel length and width, leading to a 57% reduction of average vessel size. In a pre established tumor model, moreover, 16K hPRL can significantly delay tumor development. Finally, for the first time, we provide evidence that 16K hPRL considerably reduces the establishment of B16-F10 metastasis in an experimental lung metastasis model. Both the number and size of metastases are reduced by 50% in 16K hPRL-treated mice. These results highlight a potential role for 16K hPRL in anticancer therapy for both primary tumors and metastases. PMID- 17726459 TI - Characterization of the relationship of AAV capsid domain swapping to liver transduction efficiency. AB - Recombinant adeno-associated virus (AAV) vectors show promise for use in gene therapy. For liver-targeted gene transfer in animals, AAV vectors pseudotyped with the AAV serotype 8 (AAV8) capsid have definite advantages over the widely used but less efficient serotype AAV2, even though the capsid amino acid sequences are 82% conserved. To demonstrate the mechanism behind the higher liver transduction efficiency associated with AAV8 capsids, we adopted a domain swapping strategy that would generate 27 chimeric capsid genes containing exchanged domains between AAV2 and AAV8. The resulting chimeric capsids were then used to package AAV genomes with a liver-specific human coagulation factor IX (hFIX) expression cassette. By comparing the transduction efficiencies between vectors pseudotyped with chimeric, AAV2 and AAV8 capsids, we found that the more efficient liver transduction achieved by AAV8 was closely related to the components of its interstrand Loop IV domain, particularly the subloops 1 and 4. These subloops are exposed on opposite sides of a threefold proximal peak on the virion surface, which may function as a critical structural determinant for AAV transduction. Because a single specific peptide component could not explain all the observed differences in the transduction parameters, we suggest that important subloop regions require interaction with other portions of the capsid for their functioning. PMID- 17726460 TI - Safety and immunogenicity of tyrosinase DNA vaccines in patients with melanoma. AB - Immunity to self antigens on cancer is constrained by tolerance/ignorance. DNA vaccines encoding xenogeneic differentiation antigens, such as tyrosinase (TYR), mediate tumor protection and regression in implantable mouse models, and dogs with spontaneous melanoma. We conducted a trial of mouse and human TYR DNA vaccines in stage III/IV melanoma patients. Eighteen human leukocyte antigen (HLA)-A*0201(+) melanoma patients were randomized as follows: one group received three mouse TYR DNA injections followed by three human TYR DNA injections; the other group received the same vaccines in opposite sequence. The study was conducted at three dose levels: 100, 500, and 1,500 microg DNA/injection, administered intramuscularly (IM) every 3 weeks. Most toxicities were grade 1 injection site reactions. Seven patients developed CD8(+) T-cell responses, defined by a >3 SD increase in baseline reactivity to TYR peptide in tetramer or intracellular cytokine staining (ICS) assays. There was found to be no relationship between dose, assigned schedule, and T-cell response. At a median of 42 months follow-up, median survival has not been reached. Mouse and human TYR DNA vaccines were found safe and induced CD8(+) T-cell responses in 7 of 18 patients. T cells recognizing a native TYR peptide had a phenotype consistent with that of effector memory cells. PMID- 17726461 TI - Amyloid precursor protein and amyloid beta-peptide bind to ATP synthase and regulate its activity at the surface of neural cells. AB - Amyloid precursor protein (APP) and amyloid beta-peptide (Abeta) have been implicated in a variety of physiological and pathological processes underlying nervous system functions. APP shares many features with adhesion molecules in that it is involved in neurite outgrowth, neuronal survival and synaptic plasticity. It is, thus, of interest to identify binding partners of APP that influence its functions. Using biochemical cross-linking techniques we have identified ATP synthase subunit alpha as a binding partner of the extracellular domain of APP and Abeta. APP and ATP synthase colocalize at the cell surface of cultured hippocampal neurons and astrocytes. ATP synthase subunit alpha reaches the cell surface via the secretory pathway and is N-glycosylated during this process. Transfection of APP-deficient neuroblastoma cells with APP results in increased surface localization of ATP synthase subunit alpha. The extracellular domain of APP and Abeta partially inhibit the extracellular generation of ATP by the ATP synthase complex. Interestingly, the binding sequence of APP and Abeta is similar in structure to the ATP synthase-binding sequence of the inhibitor of F1 (IF(1)), a naturally occurring inhibitor of the ATP synthase complex in mitochondria. In hippocampal slices, Abeta and IF(1) similarly impair both short- and long-term potentiation via a mechanism that could be suppressed by blockade of GABAergic transmission. These observations indicate that APP and Abeta regulate extracellular ATP levels in the brain, thus suggesting a novel mechanism in Abeta-mediated Alzheimer's disease pathology. PMID- 17726462 TI - Prevalence of human papillomavirus antibodies in young female subjects in England. AB - Sera from 1483 female subjects in England aged 10-29 years were tested. The age standardised seroprevalence was 10.7% (95% confidence intervals 9.0-12.3) for human papillomavirus (HPV) 6, 2.7% (1.8-3.6) for HPV 11, 11.9% (10.2-13.6) for HPV 16, 4.7% (3.5-5.8) for HPV 18, and 20.7% (18.6-22.7) for any of the four types. PMID- 17726463 TI - Upregulation of bfl-1 is a potential mechanism of chemoresistance in B-cell chronic lymphocytic leukaemia. AB - B-cell chronic lymphocytic leukaemia (B-CLL) is characterised by the progressive accumulation of monoclonal CD5(+) B cells. In a previous study, we have analysed the expression profile of apoptosis-regulating genes using a cDNA-based microarray and found overexpression of the antiapoptotic bcl-2 family member, bfl 1, in B-CLL cells with an apoptosis-resistant phenotype. In this study, bfl-1 mRNA levels have been determined by competitive PCR in an extended population of B-CLL patients to characterise its role in disease progression and development of chemoresistance. bfl-1 levels were significantly higher in patients with no response (NR) to last chemotherapy than in patients responding (partial response (PR)) to last chemotherapy (P<0.05) and in patients who had not required treatment (P<0.05). We found no correlation between bfl-1 mRNA levels and disease progression, IGHV mutational status or other clinical parameters. In addition, bfl-1 mRNA levels were inversely correlated with apoptotic response to in vitro fludarabine treatment of B-CLL cells. Specific downregulation of bfl-1 using siRNA induced apoptosis in resistant cells. Our data suggest that bfl-1 contributes to chemoresistance and might be a therapeutic target in B-CLL. PMID- 17726464 TI - Network-based analysis of calcium-binding protein genes identifies Grp94 as a target in human oral carcinogenesis. AB - To characterise Ca(2+) -binding protein gene expression changes in oral squamous cell carcinomas (OSCCs), we compared the gene expression profiles in OSCC-derived cell lines with normal oral tissues. One hundred Ca(2+) -binding protein genes differentially expressed in OSCCs were identified, and genetic pathways associated with expression changes were generated. Among genes mapped to the network with the highest significance, glucose-regulated protein 94 kDa (Grp94) was evaluated further for mRNA and protein expression in the OSCC cell lines, primary OSCCs, and oral premalignant lesions (OPLs). A significant (P<0.001) overexpression of Grp94 protein was observed in all cell lines compared to normal oral epithelium. Immunohistochemical analysis showed highly expressed Grp94 in primary OSCCs and OPLs, whereas most of the corresponding normal tissues had no protein immunoreaction. Real-time quantitative reverse transcriptase-PCR data agreed with the protein expression status. Moreover, overexpression of Grp94 in primary tumours was significantly (P<0.001) correlated with poor disease-free survival. The results suggested that Grp94 may have potential clinical application as a novel diagnosis and prognostic biomarker for human OSCCs. PMID- 17726465 TI - MUC-1 gene is associated with prostate cancer death: a 20-year follow-up of a population-based study in Sweden. AB - Anti-adhesion mucins have proven to play an important part in the biology of several types of cancer. Therefore, we test the hypothesis that altered expression of MUC-1 is associated with prostate cancer progression. We retrieved archival tumour tissue from a population-based cohort of 195 men with localised prostate cancer (T1a-b, Nx, M0) that has been followed for up to 20 years with watchful waiting. Semi-automated, quantitative immunohistochemistry was undertaken to evaluate MUC-1 expression. We modelled prostate cancer-specific death as a function of MUC-1 levels accounting for age, Gleason grade and tumour extent, and calculated age-adjusted and multivariate adjusted hazard ratios (HR). Men that had tumours with an MUC-intensity lower or higher than normal tissue had a higher risk of dying in prostate cancer, independent of tumour extent and Gleason score (HR 5.1 and 4.5, respectively). Adjustment for Gleason grade and tumour stage did not alter the results. Men with a Gleason score > or =7 and MUC 1 deviating from the normal had a 17 (RR=17.1 95% confidence interval=2.3-128) times higher risk to die in prostate cancer compared with men with Gleason score <7 and normal MUC-1 intensity. In summary, our data show that MUC-1 is an independent prognostic marker for prostate cancer death. PMID- 17726466 TI - Modulatory effects of heparin and short-length oligosaccharides of heparin on the metastasis and growth of LMD MDA-MB 231 breast cancer cells in vivo. AB - Expression of the chemokine receptor CXCR4 allows breast cancer cells to migrate towards specific metastatic target sites which constitutively express CXCL12. In this study, we determined whether this interaction could be disrupted using short chain length heparin oligosaccharides. Radioligand competition binding assays were performed using a range of heparin oligosaccharides to compete with polymeric heparin or heparan sulphate binding to I(125) CXCL12. Heparin dodecasaccharides were found to be the minimal chain length required to efficiently bind CXCL12 (71% inhibition; P<0.001). These oligosaccharides also significantly inhibited CXCL12-induced migration of CXCR4-expressing LMD MDA-MB 231 breast cancer cells. In addition, heparin dodecasaccharides were found to have less anticoagulant activity than either a smaller quantity of polymeric heparin or a similar amount of the low molecular weight heparin pharmaceutical product, Tinzaparin. When given subcutaneously in a SCID mouse model of human breast cancer, heparin dodecasaccharides had no effect on the number of lung metastases, but did however inhibit (P<0.05) tumour growth (lesion area) compared to control groups. In contrast, polymeric heparin significantly inhibited both the number (P<0.001) and area of metastases, suggesting a differing mechanism for the action of polymeric and heparin-derived oligosaccharides in the inhibition of tumour growth and metastases. PMID- 17726467 TI - PLD1 is overexpressed in an ER-negative MCF-7 cell line variant and a subset of phospho-Akt-negative breast carcinomas. AB - We have used a novel variant of the human oestrogen receptor (ER)-positive MCF-7 cell line, TMX2-28, as a model to study breast cancer. TMX2-28 cells show no detectable levels of mRNA or protein expression for the ER and express basal cytokeratins (CKs) 5, 14, and 17. cDNA microarray comparison between TMX2-28 and its parent cell line, MCF-7, identified 1402 differentially expressed transcripts, one of which was, phospholipase D1 (PLD1). Using real-time RT-PCR, we confirmed that PLD1 mRNA levels are 10-fold higher in TMX2-28 cells than in MCF-7 cells. We next examined PLD1 expression in human breast carcinomas. Phospholipase D1 mRNA levels were higher in breast tumours that expressed high mRNA levels of basal CKs 5 and/or 17, but PLD1 mRNA levels were not significantly higher in ER-negative tumours. Phospholipase D1 protein was overexpressed in 10 of 42 (24%) breast tumours examined by IHC. Phospholipase D1 was overexpressed in 6 of 31 ER-positive tumours and 4 of 11 ER-negative tumours. Phospholipase D1 was overexpressed in three of the four tumours that showed high CK5/17 expression. Five PLD1-positive tumours were negative for phospho-Akt expression, but positive for phospho-mammalian target of rapamycin (mTOR) expression. The other five PLD1 positive breast tumours showed positive expression for phospho-Akt; however, only two of these cases were positive for phospho-mTOR. In this study, we report that PLD1 and phospho-mTOR are coexpressed in a subset of phospho-Akt-negative breast carcinomas. PMID- 17726468 TI - Focus on emotion and disorders of emotion. AB - Regulation of emotion is becoming better understood, but despite the societal costs of disorders like depression and anxiety, their causes remain unclear. Five review articles in this issue provide perspective on this literature. PMID- 17726470 TI - Soporific signaling: how flies sleep through the night. PMID- 17726471 TI - Amygdala and neocortex: common origins and shared mechanisms. PMID- 17726472 TI - RNA decay back in play. PMID- 17726473 TI - One memory, two ways to consolidate? PMID- 17726474 TI - New insights into BDNF function in depression and anxiety. AB - The 'neurotrophin hypothesis of depression' is based largely on correlations between stress or antidepressant treatment and down- or upregulation, respectively, of brain-derived neurotrophic factor (BDNF). Genetic disruption of the signaling pathways involving BDNF and its receptor, the tyrosine kinase TrkB, does not seem to cause depressive behaviors, but does hamper the effect of antidepressant drugs. Thus, BDNF may be a target of antidepressants, but not the sole mediator of depression or anxiety. Advances in BDNF cell biology, including its transcription through multiple promoters, trafficking and secretion, may provide new insights into its role in mood disorders. Moreover, as the precursor proBDNF and the mature protein mBDNF can elicit opposite effects on cellular functions, the impact of proBDNF and its cleavage on mood should be considered. Opposing influences of mBDNF and proBDNF on long-term potentiation and long-term depression might contribute to the dichotomy of BDNF actions on behaviors mediated by the brain stress and reward systems. PMID- 17726475 TI - Social learning of fear. AB - Research across species highlights the critical role of the amygdala in fear conditioning. However, fear conditioning, involving direct aversive experience, is only one means by which fears can be acquired. Exploiting aversive experiences of other individuals through social fear learning is less risky. Behavioral research provides important insights into the workings of social fear learning, and the neural mechanisms are beginning to be understood. We review research suggesting that an amygdala-centered model of fear conditioning can help to explain social learning of fear through observation and instruction. We also describe how observational and instructed fear is distinguished by involvement of additional neural systems implicated in social-emotional behavior, language and explicit memory, and propose a modified conditioning model to account for social fear learning. A better understanding of social fear learning promotes integration of biological principles of learning with cultural evolution. PMID- 17726476 TI - Long story short: the serotonin transporter in emotion regulation and social cognition. AB - The gene encoding the serotonin transporter (5-HTT) contains a regulatory variation that has been associated with anxiety-related traits and susceptibility for depression. Here we highlight recent discoveries related to allelic variation of 5-HTT function with respect to emotion regulation and social behavior, drawing from an interdisciplinary perspective of behavioral genetics and cognitive neuroscience. Following a reductionistic path that leads from gene-behavior association studies to neuroimaging and epigenetic studies, we compare two models of 5-HTT-dependent modulation of brain activity and discuss the role of life stress experience in modifying 5-HTT function in the brain. Integration of these findings suggests that the impact of the 5-HTT gene on behavior is much broader than is commonly appreciated and may have a role in social cognition. PMID- 17726477 TI - Adult hippocampal neurogenesis in depression. AB - The development of new treatments for depression is predicated upon identification of neural substrates and mechanisms that underlie its etiology and pathophysiology. The heterogeneity of depression indicates that its origin may lie in dysfunction of multiple brain regions. Here we evaluate adult hippocampal neurogenesis as a candidate mechanism for the etiology of depression and as a substrate for antidepressant action. Current evidence indicates that adult hippocampal neurogenesis may not be a major contributor to the development of depression, but may be required for some of the behavioral effects of antidepressants. We next revisit the functional differentiation of the hippocampus along the septo-temporal axis within the context of adult hippocampal neurogenesis and suggest that neurogenesis in the ventral dentate gyrus may be preferentially involved in regulation of emotion. Finally, we speculate on how increased adult hippocampal neurogenesis may modulate dentate gyrus function to confer the behavioral effects of antidepressants. PMID- 17726481 TI - Splicing in disease: disruption of the splicing code and the decoding machinery. AB - Human genes contain a dense array of diverse cis-acting elements that make up a code required for the expression of correctly spliced mRNAs. Alternative splicing generates a highly dynamic human proteome through networks of coordinated splicing events. Cis- and trans-acting mutations that disrupt the splicing code or the machinery required for splicing and its regulation have roles in various diseases, and recent studies have provided new insights into the mechanisms by which these effects occur. An unexpectedly large fraction of exonic mutations exhibit a primary pathogenic effect on splicing. Furthermore, normal genetic variation significantly contributes to disease severity and susceptibility by affecting splicing efficiency. PMID- 17726482 TI - Deletions that reveal recessive genes. PMID- 17726478 TI - Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic. AB - Recent decades have witnessed tremendous advances in the neuroscience of emotion, learning and memory, and in animal models for understanding depression and anxiety. This review focuses on new rationally designed psychiatric treatments derived from preclinical human and animal studies. Nonpharmacological treatments that affect disrupted emotion circuits include vagal nerve stimulation, rapid transcranial magnetic stimulation and deep brain stimulation, all borrowed from neurological interventions that attempt to target known pathological foci. Other approaches include drugs that are given in relation to specific learning events to enhance or disrupt endogenous emotional learning processes. Imaging data suggest that common regions of brain activation are targeted with pharmacological and somatic treatments as well as with the emotional learning in psychotherapy. Although many of these approaches are experimental, the rapidly developing understanding of emotional circuit regulation is likely to provide exciting and powerful future treatments for debilitating mood and anxiety disorders. PMID- 17726483 TI - Searching for genes influencing a complex disease: the case of coeliac disease. AB - Recently, a few genes have been reported to be causative in inflammatory diseases. Still, we are waiting for the vast majority to be discovered. New tools for genotyping and statistical analysis have been developed and emphasis has been put on study design. Coeliac disease (CD) is a disorder, where prolamins in dietary wheat gluten and related proteins from rye or barley are not tolerated. It is one of the most common chronic diseases in humans exceeding a population prevalence of 1%. In this article, we will summarise what is currently known about the genetics influencing CD with the emphasis on the non-HLA genetic component. We will discuss some difficulties when searching for susceptibility genes in disorders with complex inheritance patterns. PMID- 17726484 TI - Simultaneous mutation scanning for gross deletions, duplications and point mutations in the DMD gene. AB - We have developed a technique to screen for gross deletions/duplications and point mutations using one streamlined approach. Fluorescent multiplex quantitative PCR is used to determine the copy number of each exon, followed by conformation sensitive capillary electrophoresis (CSCE) of the same PCR products on a multi-capillary genetic analyser. We have developed this technique to screen all 79 exons of one of the largest human genes currently known (dystrophin) using 12 multiplex PCR assays. A blind trial of 50 male and 50 female samples, in which 84 mutations had previously been found and characterized by other techniques, showed 100% sensitivity and specificity. We then applied this method to screen over 100 patient samples previously screened for deletions and duplications of 28 exons from the two hotspot regions. Our data show that combining a full deletion/duplication screen with CSCE will detect a mutation in 98% of Duchenne muscular dystrophy patients and 93% of Becker muscular dystrophy patients where the clinical diagnosis is certain. This technique is applicable to any gene and is particularly suited to mutation screening of large genes, decreasing the time taken for a complete gene screen for nearly all mutation types. PMID- 17726485 TI - Comprehensive analysis of Wolf-Hirschhorn syndrome using array CGH indicates a high prevalence of translocations. AB - Wolf-Hirschhorn syndrome (WHS) is caused by deletions involving chromosome region 4p16.3. The minimal diagnostic criteria include mild-to-severe mental retardation, hypotonia, growth delay and a distinctive facial appearance. Variable manifestations include feeding difficulties, seizures and major congenital anomalies. Clinical variation may be explained by variation in the size of the deletion. However, in addition to having a deletion involving 4p16.3, previous studies indicate that approximately 15% of WHS patients are also duplicated for another chromosome region due to an unbalanced translocation. It is likely that the prevalence of unbalanced translocations resulting in WHS is underestimated since they can be missed using conventional chromosome analyses such as karyotyping and WHS-specific fluorescence in situ hybridization (FISH). Therefore, we hypothesized that some of the clinical variation may be due to an unrecognized and unbalanced translocation. Array comparative genomic hybridization (aCGH) is a new technology that can analyze the entire genome at a significantly higher resolution over conventional cytogenetics to characterize unbalanced rearrangements. We used aCGH to analyze 33 patients with WHS and found a much higher than expected frequency of unbalanced translocations (15/33, 45%). Seven of these 15 cases were cryptic translocations not detected by a previous karyotype combined with WHS-specific FISH. Three of these 15 cases had an unbalanced translocation involving the short arm of an acrocentric chromosome and were not detected by either aCGH or subtelomere FISH. Analysis of clinical manifestations of each patient also revealed that patients with an unbalanced translocation often presented with exceptions to some expected phenotypes. PMID- 17726486 TI - A meta-analysis of association between C677T polymorphism in the methylenetetrahydrofolate reductase gene and hypertension. AB - The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene was implicated to be associated with hypertension due to its role in catalyzing the formation of 5-methylenetetrahydrofolate, a co-substrate for the conversion of homocysteine to methionine. Association studies were reported in different populations; however, a great number of subsequent studies have produced contrary results, possibly reflecting inadequate statistical power. With the cumulative data in recent years in both Caucasian and Asian populations, it was necessary to carry out a comprehensive analysis of previous findings. In this meta-analysis, we combined 26 English and Chinese studies in Caucasian and Asian populations published up to November 2006 to give a new picture of the role of the C677T polymorphism in the MTHFR gene. Evidence of significant association was detected between C677T polymorphism and hypertension in both populations. Additionally, the significant association between C677T polymorphism and hypertension/hypertension-in-pregnancy suggested that this polymorphism was one independent risk factor of hypertension. PMID- 17726487 TI - Czech dysplasia metatarsal type: another type II collagen disorder. AB - Czech dysplasia metatarsal type is an autosomal-dominant disorder characterized by an early-onset, progressive spondyloarthropathy with normal stature. Shortness of third and/or fourth toes is a frequently observed clinical feature. Similarities between individuals with this dysplasia and patients with an R275C mutation in the COL2A1 gene, prompted us to analyze the COL2A1 gene in the original families reported with Czech dysplasia. Targeted sequencing of exon 13 of the COL2A1 gene was performed, followed by sequencing of the remaining exons in case the R275C mutation was not identified. We identified the R275C substitution in two of the original patients reported with Czech dysplasia and three additional patients. All affected individuals had a similar phenotype characterized by normal height, spondyloarthropathy, short postaxial toes and absence of ocular and orofacial anomalies. The R275C mutation was excluded in a third patient reported with Czech dysplasia. However, the identification of the Y1391C mutation in this patient with disproportionate short stature made the diagnosis of spondyloperipheral dysplasia (SPD) more probable. The Y1391C mutation is located in the C-propeptide of the procollagen chain and has been reported before in a patient with the Torrance type of lethal platyspondylic skeletal dysplasia (PLSD-T). Our observation of the same Y1391C mutation in an additional unrelated patient with SPD further supports the evidence that PLSD-T and SPD represent a phenotypic continuum. The R275C mutation in the COL2A1 gene causes a specific type II collagen disorder that was recently delineated as Czech dysplasia. PMID- 17726488 TI - Molecular characterization and structural implications of 25 new ABCB4 mutations in progressive familial intrahepatic cholestasis type 3 (PFIC3). AB - Progressive familial intrahepatic cholestasis type 3 (PFIC3) is an autosomal recessive disorder due to mutations in the ATP-binding cassette, subfamily B, member 4 gene (ABCB4). ABCB4 is the liver-specific membrane transporter of phosphatidylcholine, a major and exclusive component of mammalian bile. The disease is characterized by early onset of cholestasis with high serum gamma glutamyltranspeptidase activity, which progresses into cirrhosis and liver failure before adulthood. Presently, about 20 distinct ABCB4 mutations associated to PFIC3 have been described. We report the molecular characterization of 68 PFIC3 index cases enrolled in a multicenter study, which represents the largest cohort of PFIC3 patients screened for ABCB4 mutations to date. We observed 31 mutated ABCB4 alleles in 18 index cases with 29 distinct mutations, 25 of which are novel. Despite the lack of structural information on the ABCB4 protein, the elucidation of the three-dimensional structure of bacterial homolog allows the three-dimensional model of ABCB4 to be built by homology modeling and the position of the mutated amino-acids in the protein tertiary structure to be located. In a significant fraction of the cases reported in this study, the mutation should result in substantial impairment of ABCB4 floppase activity. The results of this study provide evidence of the broad allelic heterogeneity of the disease, with causative mutations spread along 14 of the 27 coding exons, but with higher prevalence on exon 17 that, as recently shown for the closely related paralogous ABCB1 gene, could contain an evolutionary marker for mammalian ABCB4 genes in the seventh transmembrane segment. PMID- 17726489 TI - The molecular underpinnings of genetic phenomena. AB - Epiphenomena are those processes that ostensibly have no precedent at lower levels of scientific organization. In this review, it is argued that many genetic processes, including ploidy, dominance, heritability, pleiotropy, epistasis, mutational load and recombination, all are at least analogous to biochemical events that were requisite features of the RNA world. Most, if not all, of these features of contemporary whole organisms and populations may have their ultimate evolutionary roots in the chemical repertoire of catalytic RNAs. Some of these phenomena will eventually prove to be not only analogous but homologous to ribozyme activities. PMID- 17726490 TI - Molecular imaging can accelerate anti-angiogenic drug development and testing. PMID- 17726491 TI - Intracerebral hemorrhage models in rat: comparing collagenase to blood infusion. AB - Many therapies have shown promise in preclinical stroke studies, but few benefit patients. A greater understanding of stroke pathophysiology is needed to successfully develop therapies, and this depends on appropriate animal models. The collagenase and blood infusion models of intracerebral hemorrhage (ICH) are widely used; yet, investigators often prefer using one model for a variety of reasons. Thus, we directly compared these to highlight advantages and limitations of each as well as the assessment approach. An ICH was created by infusing blood or bacterial collagenase into the rats' striatum. We matched initial hematoma volume in each model (Experiment 1) and assessed the time course of bleeding (Experiment 2). Functional deficits and the progression of injury were tracked over 6 weeks using behavior, magnetic resonance imaging, and histology (Experiment 3). Despite similar initial hematoma volumes, collagenase-induced ICH resulted in a greater blood-brain barrier breakdown and more damage to the striatum, substantia nigra, white matter, and cortex. Magnetic resonance imaging revealed faster hematoma resolution in the blood model, and little increase in the volume of tissue lost from 1 to 6 weeks. In contrast, tissue loss continued over 4 weeks in the collagenase model. Finally, functional deficits recovered more quickly and completely in the blood model. This study highlights key differences between these models and that neither closely replicates the human condition. Thus, both should be used whenever possible taking into account the significant differences between these models and their limitations. Furthermore, this work illustrates significant weaknesses with several outcome measures. PMID- 17726493 TI - Paediatric liver transplantation in New Zealand: the first 5 years. AB - AIM: To report the first 5 years of paediatric liver transplantation (LTx) undertaken by the New Zealand Liver Transplant Unit. METHODS: The records of all patients aged 0 to 15 years assessed for LTx between 1 January 2002 and 1 November 2006 were examined. Demographics, criteria for listing, waiting time, transplant-hospitalisation details, and outcome to date are reported. RESULTS: Thirty-eight children were assessed for LTx, of whom 33 were listed. One improved and was de-listed, 3 died on the waiting-list, and 1 remains on the list currently. Twenty-eight children have undergone 29 transplants; there were 25 primary and 4 re-transplants (3 had their primary transplant in Australia). The median wait-time was 122 days and median age at transplantation was 2 years 6 months. Fourteen (50%) were European, 10 (36%) Maori, 3 (11%) Pacific (mostly of Samoan, Tongan, Niuean, or Cook Islands origin), and 1 (3%) Asian. The most common diagnosis was extra-hepatic biliary atresia (59%) followed by alpha-1 antitrypsin deficiency and acute liver failure (14% each). There were 6 whole liver grafts and 23 partial liver grafts including 7 live donor and 10 split LTx. Median time in the Paediatric Intensive Care Unit (PICU) was 2 days and median hospital stay after LTx was 25 days. Time spent in Auckland immediately pre- and post-transplant for families from outside the region was a median of 14 weeks. Postoperative morbidity includes biliary leaks or strictures in 10 (36%), vascular thromboses in 7 (24%), and culture positive bacterial infection in 14 (50%). Twelve (43%) experienced one or more episodes of acute rejection, 3 developed chronic rejection, and post-transplant lymphoproliferative disorder (PTLD) occurred in 2 patients. Despite these problems, graft survival is 97% and patient survival is currently 100%. All patients of school age are currently attending school. CONCLUSION: Liver transplantation is now established in New Zealand as the treatment of choice for end-stage liver disease and acute liver failure in the paediatric population. Excellent outcomes that compare well with large overseas centres have been achieved. PMID- 17726492 TI - Protective role of reactive astrocytes in brain ischemia. AB - Reactive astrocytes are thought to protect the penumbra during brain ischemia, but direct evidence has been lacking due to the absence of suitable experimental models. Previously, we generated mice deficient in two intermediate filament (IF) proteins, glial fibrillary acidic protein (GFAP) and vimentin, whose upregulation is the hallmark of reactive astrocytes. GFAP(-/-)Vim(-/-) mice exhibit attenuated posttraumatic reactive gliosis, improved integration of neural grafts, and posttraumatic regeneration. Seven days after middle cerebral artery (MCA) transection, infarct volume was 210 to 350% higher in GFAP(-/-)Vim(-/-) than in wild-type (WT) mice; GFAP(-/-), Vim(-/-) and WT mice had the same infarct volume. Endothelin B receptor (ET(B)R) immunoreactivity was strong on cultured astrocytes and reactive astrocytes around infarct in WT mice but undetectable in GFAP(-/ )Vim(-/-) astrocytes. In WT astrocytes, ET(B)R colocalized extensively with bundles of IFs. GFAP(-/-)Vim(-/-) astrocytes showed attenuated endothelin-3 induced blockage of gap junctions. Total and glutamate transporter-1 (GLT-1) mediated glutamate transport was lower in GFAP(-/-)Vim(-/-) than in WT mice. DNA array analysis and quantitative real-time PCR showed downregulation of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of tissue plasminogen activator. Thus, reactive astrocytes have a protective role in brain ischemia, and the absence of astrocyte IFs is linked to changes in glutamate transport, ET(B)R-mediated control of gap junctions, and PAI-1 expression. PMID- 17726494 TI - An outbreak of infectious syphilis in Wellington, New Zealand. AB - AIMS: To estimate the incidence of infectious syphilis in the Wellington region between 2004 and 2006, and to characterise those with infectious syphilis, in terms of demographic and risk factors, in order to inform control of the disease. METHODS: Based on information from regional laboratories, a questionnaire was sent to the requesting clinician for all individuals with positive syphilis serology between January 2004 and December 2005. The questionnaire was also used for cases of infectious syphilis seen at regional sexual health clinics in 2006. All information was recorded anonymously. RESULTS: 120 questionnaires were returned (67%), and 15 cases of infectious syphilis were identified (5 in 2004, 10 in 2005), including 3 cases not known to the sexual health clinics and hence not reported to the Institute of Environmental & Scientific Research (ESR). Another 15 cases of infectious syphilis were identified from sexual health clinic records in 2006 up to October. These 30 cases of infectious syphilis were predominantly men who have sex with men (MSM) (80%), and mainly born in New Zealand (83%). Few cases reported recent sex overseas, indicating local transmission, and anonymous partners were common. The annual incidence (per 100,000 population) of infectious syphilis is estimated at 1.3 in 2004, 2.6 in 2005, and 5.9 in 2006. CONCLUSION: Wellington is experiencing an outbreak of infectious syphilis, principally amongst MSM, but with crossover into the heterosexual community. Efforts are being made to control this outbreak through education of clinicians, partner notification, and offering screening and education in non-medical settings to at risk groups. We call on the Ministry of Health to enhance syphilis surveillance as a matter of urgency. PMID- 17726495 TI - Unplanned overnight hospital admission after strabismus surgery. AB - PURPOSE: To examine the reasons for unplanned overnight hospital admission in paediatric patients undergoing strabismus repair, to identify preventable causes (particularly postoperative nausea and vomiting), and to compare the rate of unplanned overnight stay with a group undergoing inguinal hernia repair. METHOD: A retrospective review of consecutive patients under age 17 having strabismus surgery over a 5-year period between January 1995 and December 1999 was undertaken at Christchurch Hospital, New Zealand. A control group, from a similar period, of children having elective inguinal hernia repair was used to compare the rate of overnight stay. RESULTS: 375 patients had strabismus surgery, of which 51 stayed overnight; 19 of these were from remote locations and stayed for geographic reasons only, 9 stayed overnight preoperatively only, thus leaving an unplanned overnight stay rate of 6.4%. This compared to a rate of 1.1% in those having hernia surgery. The reasons for overnight stay were postoperative nausea and vomiting (50%), anaesthetic complications (18%), late afternoon surgery (14%), social factors (14%), and pain (5%). Significant associations were found between postoperative nausea and vomiting and the extent and duration of surgery. Possible associations not reaching significance included a higher rate of postoperative nausea and vomiting in those receiving nitrous oxide, and those with evidence of stimulation of the oculo-cardiac reflex. CONCLUSIONS: The provision of suitable accommodation and careful planning of the type and timing of surgery would be expected to reduce the overnight stay rate after strabismus surgery. PMID- 17726496 TI - Five-year experience of corneal scrapes at Wellington Eye Department, New Zealand. AB - AIM: To determine the causative organisms of bacterial keratitis in Wellington and to identify the antibiotic sensitivities of each bacterium isolated. These results will then be compared with certain patient characteristics and clinical outcomes. METHODS: Corneal scrapes collected between 2001 and 2005 were retrospectively analysed and collated on a database. Corneal scrapes were collected by an ophthalmologist and processed by trained microbiological staff. RESULTS: 34 scrapes were collected; there was a positive Gram-stain in 38% of cases. A positive culture was obtained in 85% of scrapes. The commonest Gram negative organism was Moraxella spp. (12.5%). The commonest Gram-positive organism was coagulase-negative Staphylococci (25%). The Gram-negative and Gram positive bacteria were all sensitive to chloramphenicol. Ocular surface disease was the most common risk factor. CONCLUSION: Our study shows similarities and differences with other ophthalmology centres around the World, this emphasises the recognised regional variation of bacterial keratitis. The two most important points to be taken from our results are: an accurate database for recording corneal scrape details and a protocol for testing antibiotic sensitivities and resistance needs to be established in Wellington; and a future study needs to be carried out on the next five years of corneal scrapes. PMID- 17726497 TI - The Auckland City Hospital Device Point Prevalence Survey 2005: utilisation and infectious complications of intravascular and urinary devices. AB - BACKGROUND: In November 2005 a point prevalence survey of all inpatients at Auckland City Hospital was conducted to define the utilisation of intravascular and urinary devices; to measure the prevalence of infectious complications from these devices; and to provide quality assurance information about the use of these devices. METHODS: All 830 inpatients admitted on a single day under paediatric; adult medical; adult surgical, and women's health were visited by a member of the survey team and data regarding devices in situ was collected. RESULTS: Intravenous (IV) devices were present in 376/830 patients (45%; 95%CI 42 49), and 25/830 (3%; CI 2-4) had either confirmed infection or showed signs of infection. 33/830 patients (4%; CI 3-6) had intravascular devices in situ that were not required. Urinary devices were present in 93/830 patients (11%; CI 9 13), and 13/91 (14%; CI 8-23) had bacteriuria. A large proportion of urinary devices (19/91, 21%; CI 13-31) were found to have been inserted for inappropriate reasons. CONCLUSION: This study provides information on the current utilisation of devices in our hospital that can be extrapolated to other public hospitals in New Zealand. Healthcare workers require ongoing education to ensure prompt removal of devices that are not required for patient care. PMID- 17726498 TI - The challenge of paediatric obesity: more rhetoric than action. AB - A growing body of knowledge clearly shows a rapid increase in the prevalence of childhood obesity. But in spite of the many empirically-driven research projects and more laissez-faire initiatives intent on finding ways to ensure the healthy development of our young people, translating what we know into appropriate behaviour in the home, school, and community is more difficult than it sounds. It is, therefore, not surprising this concern is attracting the attention of politicians, health professionals, and educators. This article reflects on the paediatric obesity research and argues for a more coordinated effort in addressing what could (but need not) become a major public health issue. PMID- 17726499 TI - Vibrator-induced fatal rectal perforation. AB - A middle-aged man was admitted to our hospital with abdominal pain and bleeding per rectum. Subsequent laparotomy indicated an established faecal peritonitis in relation to an anterior perforation of the upper rectum. He later volunteered that he had anal intercourse 2 days previously with a vibrator at an erotic party. His partner volunteered further information regarding devient practice such as regular insertion of other foreign objects (e.g. shower hose). Tearing of the rectal mucosa following such practices is a recognised complication. However mortality following foreign body perforation is reported as extremely rare in the medical literature. Surgical repair of rectal perforation and intensive treatment did not prevent development of acute respiratory distress syndrome (ARDS) and systemic inflammatory response syndrome (SIRS) hence leading to multiple organ dysfunction syndrome (MODS) and death. This case report highlights the seriousness of rectal injuries following unusual sexual practices. Death in this case can be attributed to the late presentation and established faecal peritonitis. Death due to retroperitoneal perforation following such accidents have been reported in the literature. However previously no cases have been recorded where death occurred due to anterior rectal wall perforation. PMID- 17726500 TI - Gallbladder perforation in a patient on steroid therapy. AB - Gallbladder perforation is a serious clinical condition. A definitive diagnosis is contentious before surgery. We discuss a case where a young patient with Crohn's disease taking oral steroids presented with an acute abdomen. CT scan demonstrated a perforated gallbladder without evidence of gallstones. The patient underwent an emergency cholecystectomy and peritoneal lavage. The history and clinical findings of this patient are reviewed to highlight perforation of the gallbladder in relation to steroid therapy. PMID- 17726501 TI - Medical image. An unusual cause of shoulder pain: self-assessment questions. Synovial chondromatosis. PMID- 17726502 TI - Obesity in New Zealand children: a weighty issue. PMID- 17726503 TI - Strong forces at work on our senior doctors in New Zealand. PMID- 17726504 TI - PHARMAC responds on Herceptin assumptions and decisions. PMID- 17726505 TI - Cervical cancer prevention, feminism, and Herb Green. PMID- 17726506 TI - A tough market. PMID- 17726507 TI - Biomarkers of oxidative/nitrosative stress: an approach to disease prevention. AB - Oxidative/nitrosative stress is responsible for a variety of degenerative processes in some human diseases. Measurement of oxidatively/nitrosatively modified DNA, proteins, lipids, and sugars in biological samples has been expected to detect appropriate biomarkers for diseases in which reactive oxygen/nitrogen species are involved. Recently, the application of these biomarkers to epidemiological studies has resulted in a new discipline, molecular epidemiology, which provides the opportunity for better understanding of their causal relation with disease outcomes in a population level. In this brief review, we cover some specific biomarkers of oxidative/nitrosative stress with regard to the commonly used analytical methods for these biomarkers, their integration with epidemiology, and their application in antioxidant intervention trials, with an emphasis on those applicable to human studies and their potentialities for disease prevention. PMID- 17726508 TI - Postprandial hypotension due to a lack of sympathetic compensation in patients with diabetes mellitus. AB - Postprandial hypotension is an important hemodynamic abnormality in diabetes mellitus, but few reports are available on the relationship between autonomic dysfunction and postprandial hypotension. Ten diabetic patients and 10 healthy volunteers were recruited for this study. Postural blood pressure and heart rate changes were measured before lunch, and then the hemodynamic responses to a standardized meal were investigated. Holter electrocardiogram (ECG) monitoring was conducted for assessing spectral powers and time-domain parameters of RR variations. Postural changes from the supine to the upright position decreased the systolic blood pressure of the diabetics from 133(+/-)16 to 107(+/-)20 mmHg (p<0.01), but did not decrease the systolic blood pressure of the controls. The heart rate remained constant in the diabetics but was increased in the controls. Food ingestion decreased systolic blood pressure in the diabetics, with a maximum reduction of 25(+/-)5 mmHg. This decrease was not associated with any changes in the ratio of low frequency to high frequency, and yet the heart rate remained almost constant. Indexes involving parasympathetic tone were not affected. Food ingestion did not affect blood pressure in the control group. These findings suggest that lack of compensatory sympathetic activation is a factor contributing to postprandial hypotension in diabetics, and that parasympathetic drive does not make a significant contribution to this condition. PMID- 17726509 TI - Effects of physical and psychological stress on 5-HT2A receptor-mediated wet-dog shake responses in streptozotocin-induced diabetic rats. AB - Several epidemiological and clinical studies have indicated that the prevalence of psychiatric disorders is higher in diabetic patients than in the general population. In the present studies, we examined the behavioral changes in streptozotocin-induced diabetic rats, and investigated the effects of physical and psychological stress on the hippocampal BDNF levels and on the serotonin 2A (5-HT(2A)) receptor-mediated wet-dog shake responses. The streptozotocin (60 mg/kg, i.p.)-induced diabetes had no significant effects on the immobility time in the forced swim test or on locomotor activity in the open-field test. Moreover, there was no significant difference in the wet-dog shake responses induced by DOI, a 5-HT(2A) receptor agonist, between nondiabetic and diabetic rats. Five-day exposure to physical (electric footshock) and psychological (non footshock) stress had no significant effect on the hippocampal BDNF level in diabetic or nondiabetic rats. The 2 types of stress had no significant effect on the DOI-induced wet-dog shake responses in nondiabetic rats. In diabetic rats, the repeated exposure to physical stress markedly increased the DOI-induced wet dog shake responses, but the repeated exposure to psychological stress had no effect. These results suggest that exposure to physical stress augmented the susceptibility to the wet-dog shake responses to 5-HT(2A) receptor stimulation in streptozotocin-induced diabetic rats. PMID- 17726510 TI - Seven different glucose-6-phosphate dehydrogenase variants including a new variant distributed in Lam Dong Province in southern Vietnam. AB - We conducted a survey for glucose-6-phosphate dehydrogenase (G6PD) deficiency using blood samples from male outpatients of a local hospital in southern Vietnam. Most of the samples were from the Kinh (88.9%), the largest ethnic group in Vietnam, with a small number (11.1%) coming from the K'Ho, Chauma, Nung, and Tay minorities. We detected 25 G6PD-deficient cases among 1,104 samples (2.3%), and read the open reading frame of G6PD. A novel mutation (352T>C) predicting an aminoacid change of 118Tyr>His was found in a 1-year-old Kinh boy. His G6PD activity was estimated to be less than 10% residual activity, although he did not show chronic hemolytic anemia. Thus, we categorized this variant as Class II and named it G6PD Bao Loc. In the Kinh population, G6PD Viangchan (871G>A, 1311C>T, intron 11 nt93T>C), one of the most common variants in continental Southeast Asian populations, was the highest (6/19), followed by variants originating from the Chinese such as G6PD Canton (1376G>T) (5/19), G6PD Kaiping (1388G>A) (3/19), G6PD Gaohe (95A>G) (1/19), and G6PD Quing Yuan (392G>T) (1/19). In addition, G6PD Union (1360C>T) (2/19), which originated from the Oceania, was also detected. These findings suggest that the Kinh people are derived from various ancestries from continental Southeast Asia, China, and Oceania. In contrast, all of the 5 deficient cases in the K'Ho population were G6PD Viangchan, suggesting that they were very close to Southeast Asian populations such as the Khmer in Cambodia and the Lao in Laos. It is interesting that G6PD Mahidol (487G>A), another common variant in continental Southeast Asian populations in Myanmar, Thailand, and Malaysia, has not been detected from the Vietnamese. PMID- 17726511 TI - Autonomic dysreflexia during a bowel program in patients with cervical spinal cord injury. AB - The purpose of the present study was to investigate the relationship between bowel maneuvers and autonomic dysreflexia (AD) in patients with cervical spinal cord injuries (CSCI). Fifteen consecutive, clinically stable patients with CSCI participated. We evaluated changes in blood pressure (BP), pulse rate (PR) and classic symptoms of AD before, during and after a bowel program involving the manual removal of stool in lateral recumbency. The insertion of rectal medication induced a significant increase in systolic BP, which persisted during additional digital rectal stimulation. Furthermore, the manual removal of stool induced AD, with maximal increases of systolic BP (169.1(+-)19.5 mmHg, mean(+-)SD). However, the insertion of a finger into the anus after the end of stool flow did not cause a further increase in systolic BP. Systolic BP recovered to pre-program values within 5 min after defecation. Our study demonstrated that the combined effects of rectal and/or anal sphincter distension and uninhibited rectal contraction in response to the manual removal of stool might induce AD. We recommend avoiding, if at all possible, the manual removal of stool in order to prevent AD in patients with CSCI. PMID- 17726512 TI - Orthotopic ileal neobladder versus sigmoidal neobladder: a "quality of life" (QOL) survey. AB - To compare the quality of life (QOL) in patients with ileal neobladder and sigmoidal neobladder, a retrospective survey was conducted using a formulated questionnaire. Between January and March 1999, a QOL survey was conducted using self-administered questionnaires (EORTC QLQ-C30, IPSS, supplemented with detailed questionnaires about continence, sexual function, and patient's satisfaction with the selected urinary diversion method) for 78 patients with orthotopic urinary reservoir (OUR) who were followed-up for more than 3 months after cystectomy. Among 78 patients, 63 had OUR using an ileal segment (male/female=59/4, median age: 70.8 years old, median follow-up: 1.7 years). Fifteen patients had OUR using a sigmoidal segment (male/female=13/2, median age: 71.9, median follow-up: 3.9). The QLQ-C30 functional evaluation and the items in relation to sexual function showed no differences between the 2 groups. Concerning the voiding condition, bladder emptying, frequency, and urgency, scores in the sigmoidal OUR group were significantly higher. The QOL score concerning voiding conditions, daytime, and nighttime continence and quantity of pad showed a better score in the ileal OUR group. Concerning the satisfaction with methods of urinary diversion, patients in the sigmoidal OUR group expressed less satisfaction than their preoperative expectations. Considering several postoperative voiding conditions, ileal OUR seems superior to sigmoidal OUR. PMID- 17726513 TI - Coinfection of invasive pulmonary aspergillosis and pneumocystis jiroveci pneumonia in a non-HIV patient. AB - Invasive pulmonary aspergillosis (IPA) and pneumocystis jiroveci pneumonia (PCP) are life-threatening opportunistic infections that occur in immunocompromised hosts. Early diagnosis and treatment of these opportunistic infections is essential to the survival of immunocompromised patients. We report a 60-year-old man undergoing short-term steroid therapy after surgical resection of a brain tumor infected with combined invasive pulmonary aspergillosis and pneumocystis jiroveci pneumonia diagnosed by bronchoscopy with bronchoalveolar lavage. Our case demonstrated that short-term systemic steroid therapy in non-HIV patients with underlying chronic lung conditions and malignancies was a risk factor for IPA and PCP, and for a combination of these infections. PMID- 17726514 TI - Interphase nucleo-cytoplasmic shuttling and localization of SIRT2 during mitosis. AB - The human NAD+-dependent protein deacetylase SIRT2 resides predominantly in the cytoplasm where it functions as a tubulin deacetylase. Here we report that SIRT2 maintains a largely cytoplasmic localization during interphase by active nuclear export in a Crm1-dependent manner. We identified a functional, leptomycin B sensitive, nuclear export signal sequence within SIRT2. During the cell cycle, SIRT2 becomes enriched in the nucleus and is associated with mitotic structures, beginning with the centrosome during prophase, the mitotic spindle during metaphase, and the midbody during cytokinesis. Cells overexpressing wild-type or a catalytically inactive SIRT2 exhibit an increase in multinucleated cells. The findings suggest a novel mechanism of regulating SIRT2 function by nucleo cytoplasmic shuttling, as well as a role for SIRT2 in the nucleus during interphase and throughout mitosis. PMID- 17726515 TI - Why men matter: mating patterns drive evolution of human lifespan. AB - Evolutionary theory predicts that senescence, a decline in survival rates with age, is the consequence of stronger selection on alleles that affect fertility or mortality earlier rather than later in life. Hamilton quantified this argument by showing that a rare mutation reducing survival is opposed by a selective force that declines with age over reproductive life. He used a female-only demographic model, predicting that female menopause at age ca. 50 yrs should be followed by a sharp increase in mortality, a "wall of death." Human lives obviously do not display such a wall. Explanations of the evolution of lifespan beyond the age of female menopause have proven difficult to describe as explicit genetic models. Here we argue that the inclusion of males and mating patterns extends Hamilton's theory and predicts the pattern of human senescence. We analyze a general two-sex model to show that selection favors survival for as long as men reproduce. Male fertility can only result from matings with fertile females, and we present a range of data showing that males much older than 50 yrs have substantial realized fertility through matings with younger females, a pattern that was likely typical among early humans. Thus old-age male fertility provides a selective force against autosomal deleterious mutations at ages far past female menopause with no sharp upper age limit, eliminating the wall of death. Our findings illustrate the evolutionary importance of males and mating preferences, and show that one-sex demographic models are insufficient to describe the forces that shape human senescence. PMID- 17726516 TI - The relationship of within-host multiplication and virulence in a plant-virus system. AB - BACKGROUND: Virulence does not represent any obvious advantage to parasites. Most models of virulence evolution assume that virulence is an unavoidable consequence of within-host multiplication of parasites, resulting in trade-offs between within-host multiplication and between-host transmission fitness components. Experimental support for the central assumption of this hypothesis, i.e., for a positive correlation between within-host multiplication rates and virulence, is limited for plant-parasite systems. METHODOLOGY/PRINCIPAL FINDINGS: We have addressed this issue in the system Arabidopsis thaliana-Cucumber mosaic virus (CMV). Virus multiplication and the effect of infection on plant growth and on viable seed production were quantified for 21 Arabidopsis wild genotypes infected by 3 CMV isolates. The effect of infection on plant growth and seed production depended of plant architecture and length of postembryonic life cycle, two genetically-determined traits, as well as on the time of infection in the plant's life cycle. A relationship between virus multiplication and virulence was not a general feature of this host-parasite system. This could be explained by tolerance mechanisms determined by the host genotype and operating differently on two components of plant fitness, biomass production and resource allocation to seeds. However, a positive relationship between virus multiplication and virulence was detected for some accessions with short life cycle and high seed weight to biomass ratio, which show lower levels of tolerance to infection. CONCLUSIONS/SIGNIFICANCE: These results show that genotype-specific tolerance mechanisms may lead to the absence of a clear relationship between parasite multiplication and virulence. Furthermore, a positive correlation between parasite multiplication and virulence may occur only in some genotypes and/or environmental conditions for a given host-parasite system. Thus, our results challenge the general validity of the trade-off hypothesis for virulence evolution, and stress the need of considering the effect of both the host and parasite genotypes in analyses of host-parasite interactions. PMID- 17726517 TI - Insights from amphioxus into the evolution of vertebrate cartilage. AB - Central to the story of vertebrate evolution is the origin of the vertebrate head, a problem difficult to approach using paleontology and comparative morphology due to a lack of unambiguous intermediate forms. Embryologically, much of the vertebrate head is derived from two ectodermal tissues, the neural crest and cranial placodes. Recent work in protochordates suggests the first chordates possessed migratory neural tube cells with some features of neural crest cells. However, it is unclear how and when these cells acquired the ability to form cellular cartilage, a cell type unique to vertebrates. It has been variously proposed that the neural crest acquired chondrogenic ability by recruiting proto chondrogenic gene programs deployed in the neural tube, pharynx, and notochord. To test these hypotheses we examined the expression of 11 amphioxus orthologs of genes involved in neural crest chondrogenesis. Consistent with cellular cartilage as a vertebrate novelty, we find that no single amphioxus tissue co-expresses all or most of these genes. However, most are variously co-expressed in mesodermal derivatives. Our results suggest that neural crest-derived cartilage evolved by serial cooption of genes which functioned primitively in mesoderm. PMID- 17726518 TI - A dimer of the Toll-like receptor 4 cytoplasmic domain provides a specific scaffold for the recruitment of signalling adaptor proteins. AB - The Toll-like receptor 4 (TLR4) is a class I transmembrane receptor expressed on the surface of immune system cells. TLR4 is activated by exposure to lipopolysaccharides derived from the outer membrane of Gram negative bacteria and forms part of the innate immune response in mammals. Like other class 1 receptors, TLR4 is activated by ligand induced dimerization, and recent studies suggest that this causes concerted conformational changes in the receptor leading to self association of the cytoplasmic Toll/Interleukin 1 receptor (TIR) signalling domain. This homodimerization event is proposed to provide a new scaffold that is able to bind downstream signalling adaptor proteins. TLR4 uses two different sets of adaptors; TRAM and TRIF, and Mal and MyD88. These adaptor pairs couple two distinct signalling pathways leading to the activation of interferon response factor 3 (IRF-3) and nuclear factor kappaB (NFkappaB) respectively. In this paper we have generated a structural model of the TLR4 TIR dimer and used molecular docking to probe for potential sites of interaction between the receptor homodimer and the adaptor molecules. Remarkably, both the Mal and TRAM adaptors are strongly predicted to bind at two symmetry-related sites at the homodimer interface. This model of TLR4 activation is supported by extensive functional studies involving site directed mutagenesis, inhibition by cell permeable peptides and stable protein phosphorylation of receptor and adaptor TIR domains. Our results also suggest a molecular mechanism for two recent findings, the caspase 1 dependence of Mal signalling and the protective effects conferred by the Mal polymorphism Ser180Leu. PMID- 17726519 TI - Quadrupling muscle mass in mice by targeting TGF-beta signaling pathways. AB - Myostatin is a transforming growth factor-beta family member that normally acts to limit skeletal muscle growth. Mice genetically engineered to lack myostatin activity have about twice the amount of muscle mass throughout the body, and similar effects are seen in cattle, sheep, dogs, and a human with naturally occurring loss-of-function mutations in the myostatin gene. Hence, there is considerable interest in developing agents capable of inhibiting myostatin activity for both agricultural and human therapeutic applications. We previously showed that the myostatin binding protein, follistatin, can induce dramatic increases in muscle mass when overexpressed as a transgene in mice. In order to determine whether this effect of follistatin results solely from inhibition of myostatin activity, I analyzed the effect of this transgene in myostatin-null mice. Mstn(-/-) mice carrying a follistatin transgene had about four times the muscle mass of wild type mice, demonstrating the existence of other regulators of muscle mass with similar activity to myostatin. The greatest effect on muscle mass was observed in offspring of mothers homozygous for the Mstn mutation, raising the possibility that either myostatin itself or a downstream regulator may normally be transferred from the maternal to fetal circulations. These findings demonstrate that the capacity for increasing muscle growth by manipulating TGF-beta signaling pathways is much more extensive than previously appreciated and suggest that muscle mass may be controlled at least in part by a systemic mode of action of myostatin. PMID- 17726521 TI - Protection of hepatocytes from cytotoxic T cell mediated killing by interferon alpha. AB - BACKGROUND: Cellular immunity plays a key role in determining the outcome of hepatitis C virus (HCV) infection, although the majority of infections become persistent. The mechanisms behind persistence are still not clear; however, the primary site of infection, the liver, may be critical. We investigated the ability of CD8+ T-cells (CTL) to recognise and kill hepatocytes under cytokine stimulation. METHODS/PRINCIPLE FINDINGS: Resting hepatocytes cell lines expressed low levels of MHC Class I, but remained susceptible to CTL cytotoxicity. IFN alpha treatment, in vitro, markedly increased hepatocyte MHC Class I expression, however, reduced sensitivity to CTL cytotoxicity. IFN-alpha stimulated hepatocyte lines were still able to present antigen and induce IFN-gamma expression in interacting CTL. Resistance to killing was not due to the inhibition of the FASL/FAS- pathway, as stimulated hepatocytes were still susceptible to FAS mediated apoptosis. In vitro stimulation with IFN-alpha, or the introduction of a subgenomic HCV replicon into the HepG2 line, upregulated the expression of the granzyme-B inhibitor-proteinase inhibitor 9 (PI-9). PI-9 expression was also observed in liver tissue biopsies from patients with chronic HCV infection. CONCLUSION/SIGNIFICANCE: IFN-alpha induces resistance in hepatocytes to perforin/granzyme mediate CTL killing pathways. One possible mechanism could be through the expression of the PI-9. Hindrance of CTL cytotoxicity could contribute to the chronicity of hepatic viral infections. PMID- 17726520 TI - Phylogenomics reshuffles the eukaryotic supergroups. AB - BACKGROUND: Resolving the phylogenetic relationships between eukaryotes is an ongoing challenge of evolutionary biology. In recent years, the accumulation of molecular data led to a new evolutionary understanding, in which all eukaryotic diversity has been classified into five or six supergroups. Yet, the composition of these large assemblages and their relationships remain controversial. METHODOLOGY/PRINCIPLE FINDINGS: Here, we report the sequencing of expressed sequence tags (ESTs) for two species belonging to the supergroup Rhizaria and present the analysis of a unique dataset combining 29908 amino acid positions and an extensive taxa sampling made of 49 mainly unicellular species representative of all supergroups. Our results show a very robust relationship between Rhizaria and two main clades of the supergroup chromalveolates: stramenopiles and alveolates. We confirm the existence of consistent affinities between assemblages that were thought to belong to different supergroups of eukaryotes, thus not sharing a close evolutionary history. CONCLUSIONS: This well supported phylogeny has important consequences for our understanding of the evolutionary history of eukaryotes. In particular, it questions a single red algal origin of the chlorophyll-c containing plastids among the chromalveolates. We propose the abbreviated name 'SAR' (Stramenopiles+Alveolates+Rhizaria) to accommodate this new super assemblage of eukaryotes, which comprises the largest diversity of unicellular eukaryotes. PMID- 17726522 TI - Corpus callosum morphology in capuchin monkeys is influenced by sex and handedness. AB - Sex differences have been reported in both overall corpus callosum area and its regional subdivisions in humans. Some have suggested this reflects a unique adaptation in humans, as similar sex differences in corpus callosum morphology have not been reported in any other species of primate examined to date. Furthermore, an association between various measurements of corpus callosum morphology and handedness has been found in humans and chimpanzees. In the current study, we report measurements of corpus callosum cross-sectional area from midsagittal MR images collected in vivo from 14 adult capuchin monkeys, 9 of which were also characterized for hand preference on a coordinated bimanual task. Adult females were found to have a significantly larger corpus callosum: brain volume ratio, rostral body, posterior midbody, isthmus, and splenium than adult males. Left-handed individuals had a larger relative overall corpus callosum area than did right-handed individuals. Additionally, a significant sex and handedness interaction was found for anterior midbody, with right-handed males having a significantly smaller area than right-handed females. These results suggest that sex and handedness influences on corpus callosum morphology are not restricted to Homo sapiens. PMID- 17726523 TI - Patterns of selection in anti-malarial immune genes in malaria vectors: evidence for adaptive evolution in LRIM1 in Anopheles arabiensis. AB - BACKGROUND: Co-evolution between Plasmodium species and its vectors may result in adaptive changes in genes that are crucial components of the vector's defense against the pathogen. By analyzing which genes show evidence of positive selection in malaria vectors, but not in closely related non-vectors, we can identify genes that are crucial for the mosquito's resistance against Plasmodium. METHODOLOGY/PRINCIPLE FINDINGS: We investigated genetic variation of three anti malarial genes; CEC1, GNBP-B1 and LRIM1, in both vector and non-vector species of the Anopheles gambiae complex. Whereas little protein differentiation was observed between species in CEC1 and GNBP-B1, McDonald-Kreitman and maximum likelihood tests of positive selection show that LRIM1 underwent adaptive evolution in a primary malaria vector; An. arabiensis. In particular, two adjacent codons show clear signs of adaptation by having accumulated three out of four replacement substitutions. Furthermore, our data indicate that this LRIM1 allele has introgressed from An. arabiensis into the other main malaria vector An. gambiae. CONCLUSIONS/SIGNIFICANCE: Although no evidence exists to link the adaptation of LRIM1 to P. falciparum infection, an adaptive response of a known anti-malarial gene in a primary malaria vector is intriguing, and may suggest that this gene could play a role in Plasmodium resistance in An. arabiensis. If so, our data also predicts that LRIM1 alleles in An. gambiae vary in their level of resistance against P. falciparum. PMID- 17726524 TI - Radial glial dependent and independent dynamics of interneuronal migration in the developing cerebral cortex. AB - Interneurons originating from the ganglionic eminence migrate tangentially into the developing cerebral wall as they navigate to their distinct positions in the cerebral cortex. Compromised connectivity and differentiation of interneurons are thought to be an underlying cause in the emergence of neurodevelopmental disorders such as schizophrenia. Previously, it was suggested that tangential migration of interneurons occurs in a radial glia independent manner. Here, using simultaneous imaging of genetically defined populations of interneurons and radial glia, we demonstrate that dynamic interactions with radial glia can potentially influence the trajectory of interneuronal migration and thus the positioning of interneurons in cerebral cortex. Furthermore, there is extensive local interneuronal migration in tangential direction opposite to that of pallial orientation (i.e., in a medial to lateral direction from cortex to ganglionic eminence) all across the cerebral wall. This counter migration of interneurons may be essential to locally position interneurons once they invade the developing cerebral wall from the ganglionic eminence. Together, these observations suggest that interactions with radial glial scaffold and localized migration within the expanding cerebral wall may play essential roles in the guidance and placement of interneurons in the developing cerebral cortex. PMID- 17726525 TI - Simple sequence repeats provide a substrate for phenotypic variation in the Neurospora crassa circadian clock. AB - BACKGROUND: WHITE COLLAR-1 (WC-1) mediates interactions between the circadian clock and the environment by acting as both a core clock component and as a blue light photoreceptor in Neurospora crassa. Loss of the amino-terminal polyglutamine (NpolyQ) domain in WC-1 results in an arrhythmic circadian clock; this data is consistent with this simple sequence repeat (SSR) being essential for clock function. METHODOLOGY/PRINCIPAL FINDINGS: Since SSRs are often polymorphic in length across natural populations, we reasoned that investigating natural variation of the WC-1 NpolyQ may provide insight into its role in the circadian clock. We observed significant phenotypic variation in the period, phase and temperature compensation of circadian regulated asexual conidiation across 143 N. crassa accessions. In addition to the NpolyQ, we identified two other simple sequence repeats in WC-1. The sizes of all three WC-1 SSRs correlated with polymorphisms in other clock genes, latitude and circadian period length. Furthermore, in a cross between two N. crassa accessions, the WC-1 NpolyQ co-segregated with period length. CONCLUSIONS/SIGNIFICANCE: Natural variation of the WC-1 NpolyQ suggests a mechanism by which period length can be varied and selected for by the local environment that does not deleteriously affect WC-1 activity. Understanding natural variation in the N.crassa circadian clock will facilitate an understanding of how fungi exploit their environments. PMID- 17726526 TI - NetMHCpan, a method for quantitative predictions of peptide binding to any HLA-A and -B locus protein of known sequence. AB - BACKGROUND: Binding of peptides to Major Histocompatibility Complex (MHC) molecules is the single most selective step in the recognition of pathogens by the cellular immune system. The human MHC class I system (HLA-I) is extremely polymorphic. The number of registered HLA-I molecules has now surpassed 1500. Characterizing the specificity of each separately would be a major undertaking. PRINCIPAL FINDINGS: Here, we have drawn on a large database of known peptide-HLA I interactions to develop a bioinformatics method, which takes both peptide and HLA sequence information into account, and generates quantitative predictions of the affinity of any peptide-HLA-I interaction. Prospective experimental validation of peptides predicted to bind to previously untested HLA-I molecules, cross-validation, and retrospective prediction of known HIV immune epitopes and endogenous presented peptides, all successfully validate this method. We further demonstrate that the method can be applied to perform a clustering analysis of MHC specificities and suggest using this clustering to select particularly informative novel MHC molecules for future biochemical and functional analysis. CONCLUSIONS: Encompassing all HLA molecules, this high-throughput computational method lends itself to epitope searches that are not only genome- and pathogen wide, but also HLA-wide. Thus, it offers a truly global analysis of immune responses supporting rational development of vaccines and immunotherapy. It also promises to provide new basic insights into HLA structure-function relationships. The method is available at http://www.cbs.dtu.dk/services/NetMHCpan. PMID- 17726527 TI - Molecular characterization of a novel intracellular ADP-ribosyl cyclase. AB - BACKGROUND: ADP-ribosyl cyclases are remarkable enzymes capable of catalyzing multiple reactions including the synthesis of the novel and potent intracellular calcium mobilizing messengers, cyclic ADP-ribose and NAADP. Not all ADP-ribosyl cyclases however have been characterized at the molecular level. Moreover, those that have are located predominately at the outer cell surface and thus away from their cytosolic substrates. METHODOLOGY/PRINCIPAL FINDINGS: Here we report the molecular cloning of a novel expanded family of ADP-ribosyl cyclases from the sea urchin, an extensively used model organism for the study of inositol trisphosphate-independent calcium mobilization. We provide evidence that one of the isoforms (SpARC1) is a soluble protein that is targeted exclusively to the endoplasmic reticulum lumen when heterologously expressed. Catalytic activity of the recombinant protein was readily demonstrable in crude cell homogenates, even under conditions where luminal continuity was maintained. CONCLUSIONS/SIGNIFICANCE: Our data reveal a new intracellular location for ADP ribosyl cyclases and suggest that production of calcium mobilizing messengers may be compartmentalized. PMID- 17726528 TI - Role of transferrin receptor and the ABC transporters ABCB6 and ABCB7 for resistance and differentiation of tumor cells towards artesunate. AB - The anti-malarial artesunate also exerts profound anti-cancer activity. The susceptibility of tumor cells to artesunate can be enhanced by ferrous iron. The transferrin receptor (TfR) is involved in iron uptake by internalization of transferrin and is over-expressed in rapidly growing tumors. The ATP-binding cassette (ABC) transporters ABCB6 and ABCB7 are also involved in iron homeostasis. To investigate whether these proteins play a role for sensitivity towards artesunate, Oncotest's 36 cell line panel was treated with artesunate or artesunate plus iron(II) glycine sulfate (Ferrosanol). The majority of cell lines showed increased inhibition rates, for the combination of artesunate plus iron(II) glycine sulfate compared to artesunate alone. However, in 11 out of the 36 cell lines the combination treatment was not superior. Cell lines with high TfR expression significantly correlated with high degrees of modulation indicating that high TfR expressing tumor cells would be more efficiently inhibited by this combination treatment than low TfR expressing ones. Furthermore, we found a significant relationship between cellular response to artesunate and TfR expression in 55 cell lines of the National Cancer Institute (NCI), USA. A significant correlation was also found for ABCB6, but not for ABCB7 in the NCI panel. Artesunate treatment of human CCRF-CEM leukemia and MCF7 breast cancer cells induced ABCB6 expression but repressed ABCB7 expression. Finally, artesunate inhibited proliferation and differentiation of mouse erythroleukemia (MEL) cells. Down-regulation of ABCB6 by antisense oligonucleotides inhibited differentiation of MEL cells indicating that artesunate and ABCB6 may cooperate. In conclusion, our results indicate that ferrous iron improves the activity of artesunate in some but not all tumor cell lines. Several factors involved in iron homeostasis such as TfR and ABCB6 may contribute to this effect. PMID- 17726529 TI - Phage-Antibiotic Synergy (PAS): beta-lactam and quinolone antibiotics stimulate virulent phage growth. AB - Although the multiplication of bacteriophages (phages) has a substantial impact on the biosphere, comparatively little is known about how the external environment affects phage production. Here we report that sub-lethal concentrations of certain antibiotics can substantially stimulate the host bacterial cell's production of some virulent phage. For example, a low dosage of cefotaxime, a cephalosporin, increased an uropathogenic Escherichia coli strain's production of the phage PhiMFP by more than 7-fold. We name this phenomenon Phage Antibiotic Synergy (PAS). A related effect was observed in diverse host-phage systems, including the T4-like phages, with beta-lactam and quinolone antibiotics, as well as mitomycin C. A common characteristic of these antibiotics is that they inhibit bacterial cell division and trigger the SOS system. We therefore examined the PAS effect within the context of the bacterial SOS and filamentation responses. We found that the PAS effect appears SOS-independent and is primarily a consequence of cellular filamentation; it is mimicked by cells that constitutively filament. The fact that completely unrelated phages manifest this phenomenon suggests that it confers an important and general advantage to the phages. PMID- 17726531 TI - Kinetic analysis of Yersinia pestis DNA adenine methyltransferase activity using a hemimethylated molecular break light oligonucleotide. AB - BACKGROUND: DNA adenine methylation plays an important role in several critical bacterial processes including mismatch repair, the timing of DNA replication and the transcriptional control of gene expression. The dependence of bacterial virulence on DNA adenine methyltransferase (Dam) has led to the proposal that selective Dam inhibitors might function as broad spectrum antibiotics. METHODOLOGY/PRINCIPAL FINDINGS: Herein we report the expression and purification of Yersinia pestis Dam and the development of a continuous fluorescence based assay for DNA adenine methyltransferase activity that is suitable for determining the kinetic parameters of the enzyme and for high throughput screening against potential Dam inhibitors. The assay utilised a hemimethylated break light oligonucleotide substrate containing a GATC methylation site. When this substrate was fully methylated by Dam, it became a substrate for the restriction enzyme DpnI, resulting in separation of fluorophore (fluorescein) and quencher (dabcyl) and therefore an increase in fluorescence. The assays were monitored in real time using a fluorescence microplate reader in 96 well format and were used for the kinetic characterisation of Yersinia pestis Dam, its substrates and the known Dam inhibitor, S-adenosylhomocysteine. The assay has been validated for high throughput screening, giving a Z-factor of 0.71+/-0.07 indicating that it is a sensitive assay for the identification of inhibitors. CONCLUSIONS/SIGNIFICANCE: The assay is therefore suitable for high throughput screening for inhibitors of DNA adenine methyltransferases and the kinetic characterisation of the inhibition. PMID- 17726530 TI - Contribution of exogenous genetic elements to the group A Streptococcus metagenome. AB - Variation in gene content among strains of a bacterial species contributes to biomedically relevant differences in phenotypes such as virulence and antimicrobial resistance. Group A Streptococcus (GAS) causes a diverse array of human infections and sequelae, and exhibits a complex pathogenic behavior. To enhance our understanding of genotype-phenotype relationships in this important pathogen, we determined the complete genome sequences of four GAS strains expressing M protein serotypes (M2, M4, and 2 M12) that commonly cause noninvasive and invasive infections. These sequences were compared with eight previously determined GAS genomes and regions of variably present gene content were assessed. Consistent with the previously determined genomes, each of the new genomes is approximately 1.9 Mb in size, with approximately 10% of the gene content of each encoded on variably present exogenous genetic elements. Like the other GAS genomes, these four genomes are polylysogenic and prophage encode the majority of the variably present gene content of each. In contrast to most of the previously determined genomes, multiple exogenous integrated conjugative elements (ICEs) with characteristics of conjugative transposons and plasmids are present in these new genomes. Cumulatively, 242 new GAS metagenome genes were identified that were not present in the previously sequenced genomes. Importantly, ICEs accounted for 41% of the new GAS metagenome gene content identified in these four genomes. Two large ICEs, designated 2096-RD.2 (63 kb) and 10750-RD.2 (49 kb), have multiple genes encoding resistance to antimicrobial agents, including tetracycline and erythromycin, respectively. Also resident on these ICEs are three genes encoding inferred extracellular proteins of unknown function, including a predicted cell surface protein that is only present in the genome of the serotype M12 strain cultured from a patient with acute poststreptococcal glomerulonephritis. The data provide new information about the GAS metagenome and will assist studies of pathogenesis, antimicrobial resistance, and population genomics. PMID- 17726532 TI - TrpC3 regulates hypertrophy-associated gene expression without affecting myocyte beating or cell size. AB - Pathological cardiac hypertrophy is associated with an increased risk of heart failure and cardiovascular mortality. Calcium (Ca(2+)) -regulated gene expression is essential for the induction of hypertrophy, but it is not known how myocytes distinguish between the Ca(2+) signals that regulate contraction and those that lead to cardiac hypertrophy. We used in vitro neonatal rat ventricular myocytes to perform an RNA interference (RNAi) screen for ion channels that mediate Ca(2+) dependent gene expression in response to hypertrophic stimuli. We identified several ion channels that are linked to hypertrophic gene expression, including transient receptor potential C3 (TrpC3). RNAi-mediated knockdown of TrpC3 decreases expression of hypertrophy-associated genes such as the A- and B-type natriuretic peptides (ANP and BNP) in response to numerous hypertrophic stimuli, while TrpC3 overexpression increases BNP expression. Furthermore, stimuli that induce hypertrophy dramatically increase TrpC3 mRNA levels. Importantly, whereas TrpC3-knockdown strongly reduces gene expression associated with hypertrophy, it has a negligible effect on cell size and on myocyte beating. These results suggest that Ca(2+) influx through TrpC3 channels increases transcription of genes associated with hypertrophy but does not regulate the signaling pathways that control cell size or contraction. Thus TrpC3 may represent an important therapeutic target for the treatment of cardiac hypertrophy and heart failure. PMID- 17726533 TI - Whole blood interferon-gamma assay for baseline tuberculosis screening among Japanese healthcare students. AB - BACKGROUND: The whole blood interferon-gamma assay (QuantiFERON-TB-2G; QFT) has not been fully evaluated as a baseline tuberculosis screening test in Japanese healthcare students commencing clinical contact. The aim of this study was to compare the results from the QFT with those from the tuberculin skin test (TST) in a population deemed to be at a low risk for infection with Mycobacterium tuberculosis. METHODOLOGY/PRINCIPAL FINDINGS: Healthcare students recruited at Okayama University received both the TST and the QFT to assess the level of agreement between these two tests. The interleukin-10 levels before and after exposure to M tuberculosis-specific antigens (early-secreted antigenic target 6 kDa protein [ESAT-6] and culture filtrate protein 10 [CFP-10]) were also measured. Of the 536 healthcare students, most of whom had been vaccinated with bacillus-Calmette-Guerin (BCG), 207 (56%) were enrolled in this study. The agreement between the QFT and the TST results was poor, with positive result rates of 1.4% vs. 27.5%, respectively. A multivariate analysis also revealed that the induration diameter of the TST was not affected by the interferon-gamma concentration after exposure to either of the antigens but was influenced by the number of BCG needle scars (p = 0.046). The whole blood interleukin-10 assay revealed that after antigen exposure, the median increases in interleukin-10 concentration was higher in the subgroup with the small increase in interferon gamma concentration than in the subgroup with the large increase in interferon gamma concentration (0.3 vs. 0 pg/mL; p = 0.004). CONCLUSIONS/SIGNIFICANCE: As a baseline screening test for low-risk Japanese healthcare students at their course entry, QFT yielded quite discordant results, compared with the TST, probably because of the low specificity of the TST results in the BCG-vaccinated population. We also found, for the first time, that the change in the interleukin 10 level after exposure to specific antigens was inversely associated with that in the interferon-gamma level in a low-risk population. PMID- 17726534 TI - Detection of a microRNA signal in an in vivo expression set of mRNAs. AB - BACKGROUND: microRNAs (miRNAs) are approximately 21 nucleotide non-coding transcripts capable of regulating gene expression. The most widely studied mechanism of regulation involves binding of a miRNA to the target mRNA. As a result, translation of the target mRNA is inhibited and the mRNA may be destabilized. The inhibitory effects of miRNAs have been linked to diverse cellular processes including malignant proliferation, apoptosis, development, differentiation, and metabolic processes. We asked whether endogenous fluctuations in a set of mRNA and miRNA profiles contain correlated changes that are statistically distinguishable from the many other fluctuations in the data set. METHODOLOGY/PRINCIPAL FINDINGS: RNA was extracted from 12 human primary brain tumor biopsies. These samples were used to determine genome-wide mRNA expression levels by microarray analysis and a miRNA profile by real-time reverse transcription PCR. Correlation coefficients were determined for all possible mRNA miRNA pairs and the distribution of these correlations compared to the random distribution. An excess of high positive and negative correlation pairs were observed at the tails of these distributions. Most of these highest correlation pairs do not contain sufficiently complementary sequences to predict a target relationship; nor do they lie in physical proximity to each other. However, by examining pairs in which the significance of the correlation coefficients is modestly relaxed, negative correlations do tend to predict targets and positive correlations tend to predict physically proximate pairs. A subset of high correlation pairs were experimentally validated by over-expressing or suppressing a miRNA and measuring the correlated mRNAs. CONCLUSIONS/SIGNIFICANCE: Sufficient information exists within a set of tumor samples to detect endogenous correlations between miRNA and mRNA levels. Based on the validations the causal arrow for these correlations is likely to be directed from the miRNAs to the mRNAs. From these data sets, we inferred and validated a tumor suppression pathway linked to miR-181c. PMID- 17726535 TI - Prevalence of abnormal radiological findings in health care workers with latent tuberculosis infection and correlations with T cell immune response. AB - BACKGROUND: More than half of all health care workers (HCWs) in high TB incidence, low and middle income countries are latently infected with tuberculosis (TB). We determined radiological lesions in a cohort of HCWs with latent TB infection (LTBI) in India, and determined their association with demographic, occupational and T-cell immune response variables. METHODOLOGY: We obtained chest radiographs of HCWs who had undergone tuberculin skin test (TST) and QuantiFERON-TB Gold In Tube (QFT), an interferon-gamma release assay, in a previous cross-sectional study, and were diagnosed to have LTBI because they were positive by either TST or QFT, but had no evidence of clinical disease. Two observers independently interpreted these radiographs using a standardized data form and any discordance between them resolved by a third observer. The radiological diagnostic categories (normal, suggestive of inactive TB, and suggestive of active TB) were compared with results of TST, QFT assay, demographic, and occupational covariates. RESULTS: A total of 330 HCWs with positive TST or QFT underwent standard chest radiography. Of these 330, 113 radiographs (34.2%) were finally classified as normal, 206 (62.4%) had lesions suggestive of inactive TB, and 11 (3.4%) had features suggestive of active TB. The mean TST indurations and interferon-gamma levels in the HCWs in these three categories were not significantly different. None of the demographic or occupational covariates was associated with prevalence of inactive TB lesions on chest radiography. CONCLUSION/SIGNIFICANCE: In a high TB incidence setting, nearly two-thirds of HCWs with latent TB infection had abnormal radiographic findings, and these findings had no clear correlation with T cell immune responses. Further studies are needed to verify these findings and to identify the causes and prognosis of radiologic abnormalities in health care workers. PMID- 17726536 TI - Primary role of functional ischemia, quantitative evidence for the two-hit mechanism, and phosphodiesterase-5 inhibitor therapy in mouse muscular dystrophy. AB - BACKGROUND: Duchenne Muscular Dystrophy (DMD) is characterized by increased muscle damage and an abnormal blood flow after muscle contraction: the state of functional ischemia. Until now, however, the cause-effect relationship between the pathogenesis of DMD and functional ischemia was unclear. We examined (i) whether functional ischemia is necessary to cause contraction-induced myofiber damage and (ii) whether functional ischemia alone is sufficient to induce the damage. METHODOLOGY/PRINCIPAL FINDINGS: In vivo microscopy was used to document assays developed to measure intramuscular red blood cell flux, to quantify the amount of vasodilatory molecules produced from myofibers, and to determine the extent of myofiber damage. Reversal of functional ischemia via pharmacological manipulation prevented contraction-induced myofiber damage in mdx mice, the murine equivalent of DMD. This result indicates that functional ischemia is required for, and thus an essential cause of, muscle damage in mdx mice. Next, to determine whether functional ischemia alone is enough to explain the disease, the extent of ischemia and the amount of myofiber damage were compared both in control and mdx mice. In control mice, functional ischemia alone was found insufficient to cause a similar degree of myofiber damage observed in mdx mice. Additional mechanisms are likely contributing to cause more severe myofiber damage in mdx mice, suggestive of the existence of a "two-hit" mechanism in the pathogenesis of this disease. CONCLUSIONS/SIGNIFICANCE: Evidence was provided supporting the essential role of functional ischemia in contraction-induced myofiber damage in mdx mice. Furthermore, the first quantitative evidence for the "two-hit" mechanism in this disease was documented. Significantly, the vasoactive drug tadalafil, a phosphodiesterase 5 inhibitor, administered to mdx mice ameliorated muscle damage. PMID- 17726537 TI - Wide-scale analysis of human functional transcription factor binding reveals a strong bias towards the transcription start site. AB - BACKGROUND: Transcription factors (TF) regulate expression by binding to specific DNA sequences. A binding event is functional when it affects gene expression. Functionality of a binding site is reflected in conservation of the binding sequence during evolution and in over represented binding in gene groups with coherent biological functions. Functionality is governed by several parameters such as the TF-DNA binding strength, distance of the binding site from the transcription start site (TSS), DNA packing, and more. Understanding how these parameters control functionality of different TFs in different biological contexts is a must for identifying functional TF binding sites and for understanding regulation of transcription. METHODOLOGY/PRINCIPAL FINDINGS: We introduce a novel method to screen the promoters of a set of genes with shared biological function (obtained from the functional Gene Ontology (GO) classification) against a precompiled library of motifs, and find those motifs which are statistically over-represented in the gene set. More than 8,000 human (and 23,000 mouse) genes, were assigned to one of 134 GO sets. Their promoters were searched (from 200 bp downstream to 1,000 bp upstream the TSS) for 414 known DNA motifs. We optimized the sequence similarity score threshold, independently for every location window, taking into account nucleotide heterogeneity along the promoters of the target genes. The method, combined with binding sequence and location conservation between human and mouse, identifies with high probability functional binding sites for groups of functionally-related genes. We found many location-sensitive functional binding events and showed that they clustered close to the TSS. Our method and findings were tested experimentally. CONCLUSIONS/SIGNIFICANCE: We identified reliably functional TF binding sites. This is an essential step towards constructing regulatory networks. The promoter region proximal to the TSS is of central importance for regulation of transcription in human and mouse, just as it is in bacteria and yeast. PMID- 17726538 TI - Characterization of a family of novel cysteine- serine-rich nuclear proteins (CSRNP). AB - Gene array analysis has been widely used to identify genes induced during T cell activation. Our studies identified an immediate early gene that is strongly induced in response to IL-2 in mouse T cells which we named cysteine- serine-rich nuclear protein-1 (CSRNP-1). The human ortholog was previously identified as an AXIN1 induced gene (AXUD1). The protein does not contain sequence defined domains or motifs annotated in public databases, however the gene is a member of a family of three mammalian genes that share conserved regions, including cysteine- and serine-rich regions and a basic domain, they encode nuclear proteins, possess transcriptional activation domain and bind the sequence AGAGTG. Consequently we propose the nomenclature of CSRNP-1, -2 and -3 for the family. To elucidate the physiological functions of CSRNP-1, -2 and -3, we generated mice deficient for each of these genes by homologous recombination in embryonic stem cells. Although the CSRNP proteins have the hallmark of transcription factors and CSRNP-1 expression is highly induced by IL-2, deletion of the individual genes had no obvious consequences on normal mouse development, hematopoiesis or T cell functions. However, combined deficiencies cause partial neonatal lethality suggesting that the genes have redundant functions. PMID- 17726539 TI - GAD1 mRNA expression and DNA methylation in prefrontal cortex of subjects with schizophrenia. AB - Dysfunction of prefrontal cortex in schizophrenia includes changes in GABAergic mRNAs, including decreased expression of GAD1, encoding the 67 kDa glutamate decarboxylase (GAD67) GABA synthesis enzyme. The underlying molecular mechanisms remain unclear. Alterations in DNA methylation as an epigenetic regulator of gene expression are thought to play a role but this hypothesis is difficult to test because no techniques are available to extract DNA from GAD1 expressing neurons efficiently from human postmortem brain. Here, we present an alternative approach that is based on immunoprecipitation of mononucleosomes with anti-methyl-histone antibodies differentiating between sites of potential gene expression as opposed to repressive or silenced chromatin. Methylation patterns of CpG dinucleotides at the GAD1 proximal promoter and intron 2 were determined for each of the two chromatin fractions separately, using a case-control design for 14 schizophrenia subjects affected by a decrease in prefrontal GAD1 mRNA levels. In controls, the methylation frequencies at CpG dinucleotides, while overall higher in repressive as compared to open chromatin, did not exceed 5% at the proximal GAD1 promoter and 30% within intron 2. Subjects with schizophrenia showed a significant, on average 8-fold deficit in repressive chromatin-associated DNA methylation at the promoter. These results suggest that chromatin remodeling mechanisms are involved in dysregulated GABAergic gene expression in schizophrenia. PMID- 17726540 TI - Development of new mouse lung tumor models expressing EGFR T790M mutants associated with clinical resistance to kinase inhibitors. AB - BACKGROUND: The EGFR T790M mutation confers acquired resistance to kinase inhibitors in human EGFR mutant lung adenocarcinoma, is occasionally detected before treatment, and may confer genetic susceptibility to lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: To study further its role in lung tumorigenesis, we developed mice with inducible expression in type II pneumocytes of EGFR(T790M) alone or together with a drug-sensitive L858R mutation. Both transgenic lines develop lung adenocarcinomas that require mutant EGFR for tumor maintenance but are resistant to an EGFR kinase inhibitor. EGFR(L858R+T790M)-driven tumors are transiently targeted by hsp90 inhibition. Notably, EGFR(T790M)-expressing animals develop tumors with longer latency than EGFR(L858R+T790M)-bearing mice and in the absence of additional kinase domain mutations. CONCLUSIONS/SIGNIFICANCE: These new mouse models of mutant EGFR-dependent lung adenocarcinomas provide insight into clinical observations. The models should also be useful for developing improved therapies for patients with lung cancers harboring EGFR(T790M) alone or in conjunction with drug-sensitive EGFR kinase domain mutations. PMID- 17726541 TI - Host transcript accumulation during lytic KSHV infection reveals several classes of host responses. AB - Lytic infection by Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with an extensive shutoff of host gene expression, mediated chiefly by accelerated mRNA turnover due to expression of the viral SOX protein. We have previously identified a small number of host mRNAs that can escape SOX-mediated degradation. Here we present a detailed, transcriptome-wide analysis of host shutoff, with careful microarray normalization to allow rigorous determination of the magnitude and extent of transcript loss. We find that the extent of transcript reduction represents a continuum of susceptibilities of transcripts to virus-mediated shutoff. Our results affirm that the levels of over 75% of host transcripts are substantially reduced during lytic infection, but also show that another approximately 20% of cellular mRNAs declines only slightly (less than 2 fold) during the course of infection. Approximately 2% of examined cellular genes are strongly upregulated during lytic infection, most likely due to transcriptional induction of mRNAs that display intrinsic SOX-resistance. PMID- 17726542 TI - Insulin resistance and body fat distribution in South Asian men compared to Caucasian men. AB - OBJECTIVE: South Asians are susceptible to insulin resistance even without obesity. We examined the characteristics of body fat content, distribution and function in South Asian men and their relationships to insulin resistance compared to Caucasians. RESEARCH DESIGN AND METHODS: Twenty-nine South Asian and 18 Caucasian non-diabetic men (age 27+/-3 and 27+/-3 years, respectively) underwent euglycemic-hyperinsulinemic clamp for insulin sensitivity, underwater weighing for total body fat, MRI of entire abdomen for intraperitoneal (IP) and subcutaneous abdominal (SA) fat and biopsy of SA fat for adipocyte size. RESULTS: Compared to Caucasians, in spite of similar BMI, South Asians had higher total body fat (22+/-6 and 15+/-4% of body weight; p-value<0.0001), higher SA fat (3.5+/-1.9 and 2.2+/-1.3 kg, respectively; p-value = 0.004), but no differences in IP fat (1.0+/-0.5 and 1.0+/-0.7 kg, respectively; p-value = 0.4). SA adipocyte cell size was significantly higher in South Asians (3491+/-1393 and 1648+/-864 microm2; p-value = 0.0001) and was inversely correlated with both glucose disposal rate (r-value = -0.57; p-value = 0.0008) and plasma adiponectin concentrations (r-value = -0.71; p-value<0.0001). Adipocyte size differences persisted even when SA was matched between South Asians and Caucasians. CONCLUSIONS: Insulin resistance in young South Asian men can be observed even without increase in IP fat mass and is related to large SA adipocytes size. Hence ethnic excess in insulin resistance in South Asians appears to be related more to excess truncal fat and dysfunctional adipose tissue than to excess visceral fat. PMID- 17726543 TI - The antibacterial protein lysozyme identified as the termite egg recognition pheromone. AB - Social insects rely heavily on pheromone communication to maintain their sociality. Egg protection is one of the most fundamental social behaviours in social insects. The recent discovery of the termite-egg mimicking fungus 'termite ball' and subsequent studies on termite egg protection behaviour have shown that termites can be manipulated by using the termite egg recognition pheromone (TERP), which strongly evokes the egg-carrying and -grooming behaviours of workers. Despite the great scientific and economic importance, TERP has not been identified because of practical difficulties. Herein we identified the antibacterial protein lysozyme as the TERP. We isolated the target protein using ion-exchange and hydrophobic interaction chromatography, and the MALDI-TOF MS analysis showed a molecular size of 14.5 kDa. We found that the TERP provided antibacterial activity against a gram-positive bacterium. Among the currently known antimicrobial proteins, the molecular size of 14.5 kDa limits the target to lysozyme. Termite lysozymes obtained from eggs and salivary glands, and even hen egg lysozyme, showed a strong termite egg recognition activity. Besides eggs themselves, workers also supply lysozyme to eggs through frequent egg-grooming, by which egg surfaces are coated with saliva containing lysozyme. Reverse transcript PCR analysis showed that mRNA of termite lysozyme was expressed in both salivary glands and eggs. Western blot analysis confirmed that lysozyme production begins in immature eggs in queen ovaries. This is the first identification of proteinaceous pheromone in social insects. Researchers have focused almost exclusively on hydrocarbons when searching for recognition pheromones in social insects. The present finding of a proteinaceous pheromone represents a major step forward in, and result in the broadening of, the search for recognition pheromones. This novel function of lysozyme as a termite pheromone illuminates the profound influence of pathogenic microbes on the evolution of social behaviour in termites. PMID- 17726544 TI - Distinguishing functional amino acid covariation from background linkage disequilibrium in HIV protease and reverse transcriptase. AB - Correlated amino acid mutation analysis has been widely used to infer functional interactions between different sites in a protein. However, this analysis can be confounded by important phylogenetic effects broadly classifiable as background linkage disequilibrium (BLD). We have systematically separated the covariation induced by selective interactions between amino acids from background LD, using synonymous (S) vs. amino acid (A) mutations. Covariation between two amino acid mutations, (A,A), can be affected by selective interactions between amino acids, whereas covariation within (A,S) pairs or (S,S) pairs cannot. Our analysis of the pol gene--including the protease and the reverse transcriptase genes--in HIV reveals that (A,A) covariation levels are enormously higher than for either (A,S) or (S,S), and thus cannot be attributed to phylogenetic effects. The magnitude of these effects suggests that a large portion of (A,A) covariation in the HIV pol gene results from selective interactions. Inspection of the most prominent (A,A) interactions in the HIV pol gene showed that they are known sites of independently identified drug resistance mutations, and physically cluster around the drug binding site. Moreover, the specific set of (A,A) interaction pairs was reproducible in different drug treatment studies, and vanished in untreated HIV samples. The (S,S) covariation curves measured a low but detectable level of background LD in HIV. PMID- 17726545 TI - Locus-specific ribosomal RNA gene silencing in nucleolar dominance. AB - The silencing of one parental set of rRNA genes in a genetic hybrid is an epigenetic phenomenon known as nucleolar dominance. We showed previously that silencing is restricted to the nucleolus organizer regions (NORs), the loci where rRNA genes are tandemly arrayed, and does not spread to or from neighboring protein-coding genes. One hypothesis is that nucleolar dominance is the net result of hundreds of silencing events acting one rRNA gene at a time. A prediction of this hypothesis is that rRNA gene silencing should occur independent of chromosomal location. An alternative hypothesis is that the regulatory unit in nucleolar dominance is the NOR, rather than each individual rRNA gene, in which case NOR localization may be essential for rRNA gene silencing. To test these alternative hypotheses, we examined the fates of rRNA transgenes integrated at ectopic locations. The transgenes were accurately transcribed in all independent transgenic Arabidopsis thaliana lines tested, indicating that NOR localization is not required for rRNA gene expression. Upon crossing the transgenic A. thaliana lines as ovule parents with A. lyrata to form F1 hybrids, a new system for the study of nucleolar dominance, the endogenous rRNA genes located within the A. thaliana NORs are silenced. However, rRNA transgenes escaped silencing in multiple independent hybrids. Collectively, our data suggest that rRNA gene activation can occur in a gene-autonomous fashion, independent of chromosomal location, whereas rRNA gene silencing in nucleolar dominance is locus-dependent. PMID- 17726546 TI - A sensitive Tg assay or rhTSH stimulated Tg: what's the best in the long-term follow-up of patients with differentiated thyroid carcinoma? AB - Sensitivity of thyroglobulin (Tg) measurement in the follow-up of differentiated thyroid carcinoma (DTC) can be optimized by using a sensitive Tg assay and rhTSH stimulation. We evaluated the diagnostic yield of a sensitive Tg assay and rhTSH stimulated Tg in the detection of recurrences in the follow-up of DTC. Additionally the value of imaging techniques for the localization of recurrences was evaluated. We included 121 disease free patients in long-term follow-up for DTC (median 10 years, range 1-34). Tg during thyroid hormone suppression therapy (Tg-on) and rhTSH stimulated Tg were measured with a sensitive Tg assay. Patients with rhTSH stimulated Tg > or =1.0 ng/ml underwent imaging with neck ultrasound, FDG-PET and post therapy 131I WBS. Sensitive Tg measurement resulted in 3 patients with Tg-on > or =1.0 ng/ml, recurrence could be localized in 2 of them. RhTSH stimulation resulted in Tg > or =1.0 ng/ml in another 17 of 118 patients. Recurrence could be localized in only 1 additional patient (1 out of 118 patients). Recurrence was localized by neck ultrasound in 1 of 3, by FDG-PET in 2 of 3 and by post therapy 131I WBS in 2 of 3 patients. In the detection of recurrences in DTC, rhTSH stimulation had very limited additional value in comparison to Tg-on measurement with a sensitive Tg assay. We consider this too low to justify rhTSH stimulation in all patients during long-term follow up. Neck ultrasound, FDG-PET and post therapy 131I WBS showed complementary value in localization of disease, but were only positive in a small fracture of all procedures. PMID- 17726547 TI - Bactericidal effect of photodynamic therapy against methicillin-resistant Staphylococcus aureus strain with the use of various porphyrin photosensitizers. AB - Photodynamic therapy (PDT) is based on photosensitizers activated by light of appropriate wavelength. Their activation leads to generation of singlet oxygen and free radicals responsible for the cytotoxic effect. The aim of this project was to compare the bactericidal effect of PDT using different porphyrin photosensitizers against a methicillin-resistant Staphylococcus aureus strain. Exogenous sensitizers (protoporphyrin IX and newly synthesized derivative, protoporphyrin diarginate) induced a 3 log10-unit reduction in bacterial viable counts. With the use of endogenous, ALA-induced porphyrins, a 1.6 log10-unit reduction was obtained. The sensitizers tested executed their antibacterial activity with no essential change in the antibiotic resistance pattern of the studied strain. PMID- 17726548 TI - Elevated cyclin E level in human clear cell renal cell carcinoma: possible causes and consequences. AB - The expression of cyclin E gene (CCNE) in relation to the expression of its major regulatory protein, E2F1, was examined in clear cell renal cell carcinomas (ccRCC). We show that the overexpression of E2F1 is accompanied by the significant increase of the mean amounts of cyclin E mRNA, as well as of total cyclin E protein and its low molecular weight forms in cancer tissues as compared to peritumoral controls. A significant increase of the mean amount of total cyclin E was found in peritumoral tissues compared to cancer-free kidneys, suggesting that cancer cells might secrete factors having a profound influence on the metabolism of neighbouring tissues. A significant, positive correlations between E2F1 protein and total cyclin E mRNA, as well as between E2F1 protein and full length cyclin E protein were found in cancer-free kidneys and in peritumoral tissues, but not in ccRCCs. The overexpression of cyclin E positively correlated with the decreasing degree of tumor differentiation, implicating a role for cyclin E in the promotion of tumorigenesis. PMID- 17726550 TI - Water status monitoring of aquatic ecosystems in the context of the WFD. PMID- 17726551 TI - Coordinating links among research, standardisation and policy in support of water framework directive chemical monitoring requirements. AB - The need for coordination among scientific and policy activities is an old debate in which respective communities have often tried to impose their views rather than reflecting on pragmatic solutions. In the last few years, however, constructive exchanges have taken place in the context of expert groups linked to the implementation of the Water Framework Directive (WFD) and related EU funded research projects, which have resulted in a better understanding of communication and knowledge transfer gaps. These exchanges concern not only the way research is being interfaced with water policies, but also how improved coordination could be organised regarding technical specifications linked to standardisation. This paper discusses on-going efforts to improve coordination among research, standardisation and policy in support of WFD implementation, with emphasis on chemical monitoring requirements. PMID- 17726552 TI - Analysis of short-chain chlorinated paraffins: a discussion paper. AB - Short-chain chlorinated paraffins are a class of organic compounds widely used in many industrial applications, extensively diffused into the environment, persistent, bioaccumulative, and toxic towards aquatic organisms. However, their study and monitoring in the environment are still limited. Because of the enormous number of positional isomers that characterise their mixtures, the analysis of this class of pollutants is very difficult to perform. Beside this, the lack of certified reference materials poses a problem for the assessment of the quality assurance/quality control of any analytical procedure. At present, the scientific community does not agree on any analytical reference method, although the monitoring of short-chain chlorinated paraffins has already started in order to comply with the Water Framework Directive of the European Union on water quality. In this paper the regulatory framework, in which chlorinated paraffins are included, and the status concerning their determination are summarized. The main analytical difficulties still existing are discussed, and the definition of a method-defined parameter as well as the development of a standardised method are suggested as a way to obtain comparable monitoring data. PMID- 17726553 TI - The inadequacy of monitoring without modelling support. AB - There is much to gain in joining monitoring and modelling efforts, especially in the present process of implementing the European Water Framework Directive and in the coming implementation of the Groundwater Directive. Nevertheless, present practises in the water management world suggest that most often models are not considered an option when monitoring obligations in the WFD are solved. The present paper analyses the constraints, such as perceived insufficiency of data for modelling, lack of explicit requirement for modelling in the WFD and its associated technical guidance documents, lack of awareness about what models can do and lack of confidence in models by water managers and policy makers. The findings have mainly emerged from a series of Harmoni-CA workshops aiming at bringing the monitoring and modelling communities together for a discussion of benefits and constraints in the joint use of monitoring and modelling. The workshops were attended by scientists, water managers, policy makers, stakeholders and consultants. The overall conclusion is that modelling can significantly improve the benefits of monitoring data; by quality assurance of data, interpolation and extrapolation in space and time, development of process understanding (conceptual models), and the assessment of impacts of pressures and effects of programmes of measures. PMID- 17726554 TI - Risk assessment of contaminated sediments in river basins--theoretical considerations and pragmatic approach. AB - In order to ensure chemical quality of river basins, measures as required in the Water Framework Directive will also have to address contaminated sediments with subsequent monitoring of their successful application. Financial resources need to be allocated as part of a river basin plan to those contaminated sites that pose the biggest risk to the river basin. In order to differentiate between areas with elevated contaminant levels ("areas of concern") and those sites from which contaminated sediments can become resuspended and transported with the river, affecting the water phase and downstream sites in the catchment ("areas of risk"), the dynamics of sediment and suspended matter need to come into focus. Hydrological data have to be combined with concentration of suspended matter and its contaminant concentration to allow assessment of particle bound contaminant load. Each of these kinds of data, however, are subject to uncertainties--e.g. due to natural variability, heterogeneity of the matrix, challenges during sampling and chemical analyses of the suspended matter. Considering these uncertainties throughout the traceability chains of data collection, use of different lines of evidence and tools like fuzzy logic will increase the confidence of potentially costly management decisions. PMID- 17726556 TI - Fast characterization of non domestic load in urban wastewater networks by UV spectrophotometry. AB - Urban wastewater treatment plant efficiency, as well as biosolid quality, depends on urban wastewater quality, which can be affected by non domestic discharges (industrial, commercial etc.). The characterization of wastewater quality and non domestic discharge is complex, expensive and time consuming. However, these discharges must be controlled and reduced if possible. The development of a simple and fast methodology, namely based on alternative methods such as UV spectrophotometry, has been carried out and applied to different areas of a medium sized town of Southern Quebec (Canada). Several autosamplers and on line/on site measurements have been used in critical control points of the network areas, for a dry weather campaign in four areas (industrial, commercial, hospital and university). The flow rate study, completed by the exploitation of conductivity measurements and the qualitative examination of UV spectra allows the discrimination of non domestic loads and their variability study from one point to another. The identification of critical discharges and organic shock loads has been possible with low investment, and mitigation actions have been proposed. PMID- 17726555 TI - Intra-laboratory evaluation of Microbial Assay for Risk Assessment (MARA) for potential application in the implementation of the Water Framework Directive (WFD). AB - The Microbial Assay for Risk Assessment (MARA) is an innovative system based on an array of 11 different microbial species freeze-dried in a 96-well micro-titre plate format. Developed for testing the toxicity of chemicals, mixtures and environmental samples, the assay employs species of a taxonomically diverse range. In addition to ten prokaryotic species, a eukaryote (yeast) is included in the range. The MARA's innate scope of a multi-dimensional test allows determination of toxicity based on a unique assay fingerprint or index, numerically expressed as the mean Microbial Toxic Concentration (MTC). The most significant potential of the test is in the additional inference that can be conveyed to the toxicity evaluation because of the presence of each of the constituent species. In view of the fact that conventional aquatic bioassays, like fish or cladoceran tests, are expensive and impractical, the MARA could provide a cost-effective solution for routine ecotoxicological testing. The performance of the MARA was evaluated to ascertain its capability and potential scope. Sensitivity to toxicants and different environmental samples was assessed. Evaluation included comparison with other tests: namely Microtox, invertebrate (Daphnia magna and Thamnocephalus platyurus) microbiotests, and respiration inhibition and nitrification-inhibition tests. The most sensitive invertebrate test was found to be the T. platyurus microbiotest for three of the four metals tested. The LC(50) values for this test for Cd(ii), Cr(vi) and As(iii) were 0.2, 0.018 and 0.3 mg l(-1), respectively; and the corresponding most sensitive MARA species MTC values were 4.4, 2.8 and 17 mg l(-1), respectively. PMID- 17726557 TI - Design of a new monitoring network and first testing of new biological assessment methods according to water framework directive. AB - In most European member states, more or less completely new monitoring networks and assessment methods had to be developed as basic technical tools for the implementation of the EU Water Framework Directive (WFD). In the river basin of the Stever, the largest tributary to the river Lippe (River Rhine, Northrhine Westphalia, Germany), a WFD-monitoring network was developed, and new German biological methods for rivers, developed for the purposes of the WFD, have been applied. Like most rivers in the German lowland areas, nearly all the river courses of the Stever system are altered by hydro-morphological degradation (straightening, bank fixation, lack of canopy etc.). In 2005 and 2006, the biological quality components of macroinvertebrates, fish and macrophytes were investigated and evaluated for the assessment of the ecological status of about 50 surface water bodies within the whole Stever system. Basic physical and chemical parameters, as well as priority substances, have been analysed in the same period. In this contribution, the design of the new monitoring network, the core principles of the German biological methods, and the most important results of the pilot monitoring will be presented. As main impacts with severe effects on the faunal and floral communities, the many migration barriers and the bad quality of the river morphology could be stated. Organic pollution is no more a severe problem in the Stever. The pilot project was successfully conducted in close collaboration with the water authorities (District Government Munster) and the water association Lippeverband. PMID- 17726558 TI - Water quality indices across Europe--a comparison of the good ecological status of five river basins. AB - The European Water Framework Directive (WFD) requires the definition of near natural reference conditions to determine the extent of water bodies' deviation from "good ecological status" caused by stress gradients. However, the classification of ecological quality depends on the assessment method applied and the stressor concerned. While assessment methods that are generally applicable would be favourable, many European countries employ the locally developed water quality metrics that assess the impact of organic pollution (including eutrophication) and the associated decrease in dissolved oxygen. These indices do not specifically address stress from organic toxicants, such as pesticides. The aim of this study was to examine the performance of presently used assessment methods to identify reference conditions of non-contaminated streams in five selected European river basins, covering the geographical region from Spain to Finland, as a crucial prerequisite to indicate toxic gradients. The analysis comprised the Belgium biotic index (BBI), the biological monitoring working party (BMWP) scoring system and the revised German saprobic index. For comparison, we included an adaptation of the recently developed SPEAR index. In two previous field studies, this metric highly correlated with measured pesticide gradients. In this study, SPEAR was the only indicator that was generally applicable to all monitoring data and capable of determining "high ecological status" of reference conditions in all basins. Thus, based upon previous and own results, the authors suggest the species at risk (SPEAR) index to be potentially useful as a European wide index to address deviations from "good ecological status" due to organic toxicants and recommend it for consideration in integrated water-resource evaluations under the WFD. PMID- 17726559 TI - Biomonitoring with Gammarus pulex at the Meuse (NL), Aller (GER) and Rhine (F) rivers with the online Multispecies Freshwater Biomonitor. AB - Biological early warning systems represent a set of tools that may be able to respond to certain chemical monitoring requirements of recent European legislation, the Water Framework Directive (WFD2000/60/EC), that aims to improve and protect water quality across Europe. In situ biomonitoring was performed along the rivers Meuse (NL), Aller (GER) and Rhine (F) within the frame of the European Union-funded Project SWIFT-WFD. Gammarus pulex was used as a test organism during the evaluation of the Multispecies Freshwater Biomonitor(R) (MFB), an online biomonitor to quantitatively record different behaviour patterns of animals. At the river Meuse G. pulex reacted to pulse exposure of either a mixture of trace metals or of several organic xenobiotics, by showing up to 20% decreased locomotory activity (already at the 1st pulse) and increased mortality (at 2nd or 3rd pulse only). G. pulex deployed within the MFB system were observed to survive well at the monitoring station on the Aller (100%) and monitoring did not result in the measurement of chemical irregularities. In contrast, deployment at the monitoring station on the Rhine river demonstrated that the test organism was able to detect chemical irregularities by up to 20% decreased locomotory activity in the animals. The MFB proved to be an alert system for water quality monitoring at sensitive sites and sites with accidental pollution. PMID- 17726560 TI - An overview of pharmaceuticals and personal care products contamination along the river Somes watershed, Romania. AB - The mass flows of selected pharmaceuticals and personal care products (PPCPs) were studied in the aqueous compartment of the river Somes in Romania. PPCPs were measured in wastewater treatment effluents and in the receiving river water. The analytical method for the determination of PPCPs in river water was based on solid phase extraction and GC-ITMS. Carbamazepine, pentoxyfylline, ibuprofen, diazepam, galaxolide, tonalide and triclosan were determined in wastewater effluents with individual concentrations ranging from 15 to 774 ng L(-1). Caffeine was measured at concentrations up to 42 560 ng L(-1). Due to the high contamination of WWTP effluents, the receiving river was also polluted. The most abundant PPCPs measured in the Somes were caffeine, galaxolide, carbamazepine and triclosan. They were present at all the 15 sampling sites along the Somes, the concentrations ranging from 10 to 400 ng L(-1). The concentrations in the effluents of the different wastewater treatment plants (WWTPs) varied considerably and the differences are due to different elimination efficiencies of the studied PPCPs during sewage treatment. Only one of 5 WWTPs studied, the WWTP in Cluj-Napoca, was working properly, and therefore technical measures have to be taken for upgrading the WWTPs and reducing the environmental load of micropollutants. This study is the first overview of PPCPs along on Romanian part of river Somes. PMID- 17726561 TI - The sensitive and selective determination of aluminium by spectrofluorimetric detection after complexation with N-o-vanillidine-2-amino-p-cresol. AB - A simple, easy to use and selective spectrofluorimetric method for the determination of trace levels of aluminium has been developed. A new Schiff base, N-o-vanillidine-2-amino-p-cresol (OVAC), has been synthesized and its fluorescence activity with aluminium investigated. Based on this chelation reaction, a spectrofluorimetric method has been developed for the determination of aluminium in samples buffered at pH 4.0 using acetic acid-sodium acetate. The chelation reaction between Al(iii) and N-o-vanillidine-2-amino-p-cresol was very fast, requiring only 20 min at room temperature to complex completely. The excitation and emission wavelengths were 423.0 and 553.0 nm, respectively, at which the OVAC-Al complex gave the maximum fluorescence intensity at pH 4.0 in a 50% ethanol-50% water medium. The interference from fluoride ions was minimized by the addition of Be(2+). Other ions were found not to interfere at the concentrations likely to be found in natural waters. Under these conditions, the calibration plot was linear up to 1000 microg L(-1) (r = 0.999). The limit of detection (3sigma) for the determination of Al(iii) was 0.19 microg L(-1) and the precision for multiple determinations of 3 ng mL(-1) Al(iii) prepared in ultra pure water was found to be 0.29% (n = 16). The Schiff base ligand could be used to determine ultra-trace aluminium from natural waters. Analysis of environmental certified reference materials showed good agreement with the certified values. The procedure was found to be equally applicable to both fresh water and saline solutions (including sea water) using either normal external calibration or the standard additions method. PMID- 17726563 TI - Multi-residues analysis of pre-emergence herbicides in fluvial sediments: application to the mid-Garonne River. AB - Contamination of man and ecosystems by pesticides has become a major environmental concern. Whereas many studies exist on contamination from agriculture, the effects of urban sources are usually omitted. Fluvial sediment is a complex matrix of pollutants but little is known of its recent herbicide content. This study proposes a method for a fast and reliable analysis of herbicides by employing the accelerated solvent extractor (ASE). The aim of the study is to show the impact of a major town (Toulouse) on the herbicide content in the river. In this study, three herbicide families (i.e.s-triazine, substituted ureas and anilides) were analysed in fluvial sediment fractions at 11 sampling sites along the mid-Garonne River and its tributaries. River water contamination by herbicides is minor, except for at three sites located in urban areas. Among the herbicidal families studied, urban and suburban areas are distinguished from rural areas and were found to be the most contaminated sites during the study period, a winter low-water event. The herbicide content of the coarse sediment fractions is about one third of that found in the fine fractions and usually ignored. The distribution of pesticide concentrations across the whole range of particle sizes was investigated to clarify the role of plant remains on the significant accumulation in the coarse fractions. PMID- 17726562 TI - Soil pollution by PAHs in urban soils: a comparison of three European cities. AB - The purpose of this study was to determine the degree of contamination with polycyclic aromatic hydrocarbons (PAHs) in samples of urban soil from three European cities: Glasgow (UK), Torino (Italy) and Ljubljana (Slovenia). Fifteen PAHs (naphthalene, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene, benzo[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, dibenzo[a,h]anthracene, benzo[g,h,i]perylene, indeno[1,2,3-c,d]pyrene) were measured in urban soil samples, using harmonised sampling, sample extraction and analyte quantification methods. Although the mean concentration of each PAH in urban soils of each city showed a wide range of values, high levels of contamination were only evident in Glasgow, where the sum of concentrations of 15 PAHs was in the range 1487-51,822 microg kg(-1), cf. ranges in the other two cities were about ten-fold lower (89.5 4488 microg kg(-1)). The three predominant PAHs were phenanthrene, fluoranthene and pyrene, with the sum of these compounds about 40% of the total PAH content. These data, together with some special molecular indices based on ratios of selected PAHs, suggest pyrogenic origins, especially motor vehicle exhausts, to be the major sources of PAHs in urban soils of the three cities. The largest concentrations for PAHs were often found in sites close to the historic quarters of the cities. Overall, the different climatic conditions, the organic carbon contents of soil, and the source apportionment were the dominant factors affecting accumulation of PAHs in soil. PMID- 17726564 TI - Spatial and temporal trends of polycyclic aromatic hydrocarbons in wild mussels from the Cantabrian coast (N Spain) after the Prestige oil spill. AB - Polycyclic aromatic hydrocarbon (PAH) levels were determined in tissues of wild mussels (Mytilus galloprovincialis) collected at 17 stations along the Cantabrian coast (N Spain), from Navia (Asturias) to Fuenterrabia (Basque Country), in order to assess the extent of the environmental impact caused by the Prestige oil spill (November 13, 2002). Six sampling campaigns were carried out in April, June and November in 2003 and 2004. The comparison of PAH data with those obtained earlier in 2000 showed a widespread pyrolytic and petrogenic contamination and allowed an estimation, for the first time, of the background pollution in the region and identification of the chronic hotspots. The spatial distribution found in the first samples after the oil spill revealed the eastern area as the most affected due to the continuous arrival of fuel slicks since early summer 2003. Several stations in this area showed increased total PAH concentrations of up to 15 times the pre-spill levels, which did not recover until April 2004, more than one year after the accident. Molecular parameters within the aliphatic and aromatic fractions were determined to assess the presence of Prestige oil in these samples. PMID- 17726565 TI - Transvaginal vs transobturator approach for synthetic sling placement in patients with stress urinary incontinence. AB - We present comparative short-term experience with the transvaginal (TVT) and the transobturator (TVT-O) approaches for the treatment of stress urinary incontinence (SUI). We studied 315 women with SUI, treated with a tension-free tape placement. The TVT approach was applied in 265 women, while 50 women were treated by the TVT-O approach. The mean operation time was 25 and 17 min in the TVT and TVT-O group, respectively (p<0.001). In the TVT group, continence rates were 87% after 1 year, while in the TVT-O group, the continence rate was 94%. Postoperative pain was reported in 14.4 and 28% of the TVT and TVT-O patients, respectively (p=0.02). Complications such as bladder perforation, retropubic hematoma, and urinary retention took place only in the TVT group. Urinary tract infections were recorded in 20 and 8% of the TVT and TVT-O patients, respectively (p=0.04), while vaginal erosion took place in 1.5 and 2% and de novo urgency in 14 and 8%. Both approaches show high rates of cure at the first postoperative year, while complications are less with the TVT-O procedure. PMID- 17726566 TI - Urodynamic changes after tension-free sling procedures: Mycromesh-Plus vs TVT sling. AB - Assortments of suburethral sling procedures have become increasingly important in the treatment of stress urinary incontinence (SUI). This study compared a consecutive series of patients undergoing two types of no-tension, midurethral sling procedures: a traditional pubovaginal technique and graft (modified polytetrafluoroethylene graft; Mycromesh-Plus [MMP]) and the more recently introduced tension-free vaginal tape (TVT) sling. We observed for differences in success rates, urodynamic parameters, and complications of the two procedures. One group received a MMP sling, which was placed at the midurethra without tension. The other group underwent a minimally invasive TVT sling. Multichannel urodynamic studies were performed pre- and postoperatively. Cure rates for SUI were similar for the two groups (95 vs 95%). Urgency and urge incontinence symptoms improved substantially in both groups. Comparison of pre- and postoperative urodynamic indices demonstrated no differences in changes in average functional urethral lengths, changes in maximum urethral closure pressures, or improvement in pressure transmission ratios. Both groups showed a decrease in urethral mobility postoperatively. However, the TVT group demonstrated a lesser degree of change. While the TVT group did spontaneously void earlier than the MMP group (5.7 vs 9.7 days, p < 0.05), this did not result in significantly different postvoid residual volumes (71 vs 101 mL). Complications, including need for self-catheterization and sling revision or removal, and urinary tract infections also were fewer in the TVT group. This study demonstrated that the TVT sling affords an equivalent cure of SUI with similar urodynamic changes but significantly fewer complications than the more traditional MMP sling. PMID- 17726567 TI - Variation in the BMP2 gene: bone mineral density and ultrasound in young adult and elderly women. AB - Bone morphogenetic protein-2 (BMP2) plays a key role in bone formation and maintenance. Studies of polymorphisms within the gene in relation to bone mineral density (BMD) and fracture have been inconsistent. Our aim was to investigate associations between polymorphisms in the BMP2 gene and bone mass, fracture, and quantitative ultrasound (QUS) measures at different stages of skeletal development. Study subjects were participants of two population-based cohorts of Swedish women: the PEAK-25 cohort of young adult women aged 25 years (n = 993) and the OPRA cohort of elderly women aged 75 years (n = 1,001). We analyzed four single-nucleotide polymorphisms (SNPs) across the BMP2 gene including the Ser37Ala SNP previously identified in relation to BMD, QUS of the calcaneus, and, in the elderly women, fracture. BMP2 gene variations were associated with QUS of bone, independent of BMD, but only in the young women. Even after adjusting for confounding factors, SNP rs235754 in the 3' region of the gene was significantly associated with the ultrasound parameters speed of sound (P = 0.003) and stiffness (P = 0.002). The 5' SNP rs235710 showed trends for QUS parameters (P = 0.02-0.07). No association with BMP2 SNPs was observed in either cohort for either BMD or fracture. While further, more extensive genotyping across the gene is recommended, as we may not have captured all information, our preliminary data suggest that variation in BMP2 may play a previously unidentified role in aspects of bone quality, which may be age- and site-dependent. PMID- 17726568 TI - Lessons from a beetle and an ant: coping with taxon-dependent differences in microsatellite development success. AB - Microsatellites are powerful markers often isolated de novo for species yet to be investigated. Enriched genomic libraries are usually used for isolation purposes. We critically evaluate the outcome of an enrichment-based protocol applied to two insect species (the ant Lasius austriacus and the beetle Pityogenes chalcographus) which yielded contrasting numbers of suitable loci. Our findings of differences in microsatellite isolation are consistent with the available data on differences in genomic characteristics across these taxa. In the beetle repeated isolation of identical motifs, difficulties in primer development, and multibanded products caused loss of most candidate clones. We identified critical steps during marker development. PMID- 17726569 TI - Protein disulfide oxidoreductases and the evolution of thermophily: was the last common ancestor a heat-loving microbe? AB - Protein disulfide oxidoreductases (PDOs) are redox enzymes that catalyze dithiol disulfide exchange reactions. Their sequences and structure reveal the presence of two thioredoxin fold units, each of which is endowed with a catalytic site CXXC motif. PDOs are the outcome of an ancient gene duplication event. They have been described in a number of thermophilic and hyperthermophilic species, where they play a critical role in the structural stabilization of intracellular proteins. PDOs are homologous to both the N-terminal domain of the bacterial alkyl hydroperoxide reductase (AhpF) and to the eukaryotic protein disulfide isomerase (PDI). Phylogenetic analysis of PDOs suggests that they first evolved in the crenarchaeota, spreading from them into the Bacteria via the euryarchaeota. These results imply that the last common ancestor (LCA) of all extant living beings lacked a PDO and argue, albeit weakly, against a thermophilic LCA. PMID- 17726570 TI - Comparison of insulin monotherapy and combination therapy with insulin and metformin or insulin and rosiglitazone or insulin and acarbose in type 2 diabetes. AB - The aim of this study was to compare the efficacy of treatment with insulin alone, insulin plus acarbose, insulin plus metformin, or insulin plus rosiglitazone in type 2 diabetic subjects who were previously on insulin monotherapy, and to evaluate the effects of these treatments on cardiovascular risk factors including lipid profile, C-reactive protein (CRP) and fibrinogen. Sixty-six poorly controlled type 2 diabetic patients on insulin monotherapy were involved. They were randomized to insulin alone, insulin plus acarbose, insulin plus metformin, or insulin plus rosiglitazone groups for 6 months period. Mean fasting and postprandial glucose values as well as HbA1c levels significantly decreased in all groups. The greatest improvement in HbA1c was observed in insulin plus rosiglitazone (2.4%) and in insulin plus metformin (2%) groups. Daily total insulin dose was increased to 12.7 units/day in insulin alone group, decreased to 4.7 units/day in insulin plus rosiglitazone group, to 4.2 units/day in insulin plus metformin group, and to 2.7 units/day in insulin plus acarbose group. Least weight gain occurred in insulin plus metformin group (1.4 kg) and greatest weight gain occurred in insulin plus rosiglitazone group (4.6 kg). No significant change in lipid levels--except serum triglycerides--was observed in any groups. CRP and fibrinogen levels decreased in all groups, but the decrease in fibrinogen level was significantly greater in insulin plus rosiglitazone group. All groups were comparable in hypoglycemic episodes. No serious adverse event was noted in any group. PMID- 17726571 TI - Insulin, glucose and glycated hemoglobin in Alzheimer's and vascular dementia with and without superimposed Type II diabetes mellitus condition. AB - Increased concentrations of insulin, glucose and glycohemoglobin are associated with Type II diabetes mellitus (DM) and recognized as characteristic markers of the disease; in Alzheimer's (AD), Vascular dementia (VaD), and both dementia's with superimposed diabetes (AD + DM, VaD + DM) the knowledge is scarce. The sample (n = 122; males = 60; mean age = 73 +/- 7) comprised DM, AD, VaD, AD + DM, and VaD + DM patients, and healthy controls (C). The ANOVA's yielded significant differences between groups: Insulin p = 3.7 x 10(-3); Glucose p < 10(-12); Glycohemoglobin p = 9.2x10(-4). Comparisons between groups (DM vs. C, AD + DM vs. AD, VaD + DM vs. VaD, and demented DM vs. non-demented DM) resulted significant for all variables (Bonferroni's statistic, alpha = 0.05). Diabetic and diabetic demented patients presented significant increases largely different from controls (0.01 < p < 0.001), unlike the non-significant changes in their non-diabetic counterparts; linear relationships were found across all groups. The correlation's insulin/glucose and insulin/glycohemoglobin change to positive within demented groups, indicating a different performance of insulin in demented and non-demented subjects. PMID- 17726572 TI - Chemical architecture of the posterior striatum in the human brain. AB - The neurochemical organization of the posterior caudate nucleus (CN) (body, gyrus and tail) and putamen (Put) was analyzed in the human brain using adjacent sections stained for acetylcholinesterase (AChE), limbic system-associated membrane protein (LAMP), enkephalin (ENK), parvalbumin (PV), calbindin (CB) and tyrosine hydroxylase (TH). Striosomes were visualized in all striatal regions but the anterior two thirds of the CN tail. They were highly immunoreactive (-ir) for ENK and LAMP, devoid of PV and AChE staining, and surrounded by a ring of tissue with pale TH- and CB-ir neuropil. In the Put, other rings of tissue completely free of ENK labeling surrounded certain striosomes (clear septa). In the CN body, gyrus and tail some markers revealed gradients and heterogeneities along the dorsoventral and mediolateral axes. A rim of striatal tissue densely stained for ENK and LAMP and poorly labeled for PV was noticeable along the lateral edge of the Put and the dorsolateral sector of the CN body. Our results illustrate a chemical architecture in the posterior striatum that is heterogeneous and slightly different from that found in the more anterior striatum. PMID- 17726573 TI - Phylogenetic analysis of type I polyketide synthase and nonribosomal peptide synthetase genes in Antarctic sediment. AB - The modular polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) have been found to be involved in natural product synthesis in many microorganisms. Study on their diversities in natural environment may provide important ecological insights, in addition to opportunities for antibacterial drugs development. In this study, the PKS and NRPS gene diversities in two coast sediments near China Zhongshan Station were studied. The phylogenetic analysis of amino acid (AA) sequences indicated that the identified ketosynthase (KS) domains were clustered with those from diverse bacterial groups, including Proteobacteria, Firmicutes, Planctomycetes, Cyanobacteria, Actinobacteria, and some uncultured symbiotic bacteria. One new branch belonging to hybrid PKS/NRPS enzyme complexes and five independent clades were found on the phylogenetic tree. The obtained adenylation (A) domains were mainly clustered within the Cyanobacteria and Proteobacteria group. Most of the identified KS and A domains showed below 80 and 60% identities at the AA level to their closest matches in GenBank, respectively. The diversities of both KS and A domains in natural environmental sample were different from those in sewage-contaminated sample. These results revealed the great diversity and novelty of both PKS and NRPS genes in Antarctic sediment. PMID- 17726574 TI - Mannosylglycerate is essential for osmotic adjustment in Thermus thermophilus strains HB27 and RQ-1. AB - We disrupted the mpgS encoding mannosyl-3-phosphoglycerate synthase (MpgS) of Thermus thermophilus strains HB27 and RQ-1, by homologous recombination, to assess the role of the compatible solute mannosylglycerate (MG) in osmoadaptation of the mutants, to examine their ability to grow in NaCl-containing medium and to identify the intracellular organic solutes. Strain HB27 accumulated only MG when grown in defined medium containing 2% NaCl; mutant HB27M9 did not grow in the same medium containing more than 1% NaCl. When trehalose or MG was added, the mutant was able to grow up to 2% of NaCl and accumulated trehalose or MG, respectively, plus amino acids. T. thermophilus RQ-1 grew in medium containing up to 5% NaCl, accumulated trehalose and lower amounts of MG. Mutant RQ-1M1 lost the ability to grow in medium containing more than 3% NaCl and accumulated trehalose and moderate levels of amino acids. Exogenous MG did not improve the ability of the organism to grow above 3% NaCl, but caused a decrease in the levels of amino acids. Our results show that MG serves as a compatible solute primarily during osmoadaptation at low levels of NaCl while trehalose is primarily involved in osmoadaptation during growth at higher NaCl levels. PMID- 17726575 TI - The opsins of the vertebrate retina: insights from structural, biochemical, and evolutionary studies. AB - The vertebrate retina contains several classes of visual pigments responsible for such diverse functions as image- and nonimage-forming vision, the entrainment of circadian cycles, and the pupilary light response. With vision being vital to the survival of many species, the elucidation of the structural and biochemical properties of visual pigments has been the focus of a large body of research that has led to rapid advances in the field of photoreception. In this review, the current understanding of the structure, function, biochemistry, and evolution of the opsins that make up the photopigments in the vertebrate retina will be reviewed. These include the rod and cone opsins, melanopsin, RGR, peropsin, and VA-opsin. The goal is to highlight important questions that have been answered and to define some of the remaining questions in the field that will provide future directions for research. PMID- 17726576 TI - Polyphenolic phytochemicals--just antioxidants or much more? AB - Polyphenolic phytochemicals are ubiquitous in plants, in which they function in various protective roles. A 'recommended' human diet contains significant quantities of polyphenolics, as they have long been assumed to be 'antioxidants' that scavenge excessive, damaging, free radicals arising from normal metabolic processes. There is recent evidence that polyphenolics also have 'indirect' antioxidant effects through induction of endogenous protective enzymes. There is also increasing evidence for many potential benefits through polyphenolic mediated regulation of cellular processes such as inflammation. Inductive or signalling effects may occur at concentrations much lower than required for effective radical scavenging. Over the last 2-3 years, there have been many exciting new developments in the elucidation of the in vivo mechanisms of the health benefits of polyphenolics. We summarise the current knowledge of the intake, bio-availability and metabolism of polyphenolics, their antioxidant effects, regulatory effects on signalling pathways, neuro-protective effects and regulatory effects on energy metabolism and gut health. PMID- 17726577 TI - Regulatory mechanisms of mitogen-activated kinase signaling. AB - MAP kinases (MAPKs) are evolutionarily conserved regulators that mediate signal transduction and play essential roles in various physiological processes. There are three main families of MAPKs in mammals, whose functions are regulated by activators, inactivators, substrates and scaffolds, which together form delicate signaling cascades in response to different extracellular or intracellular stimulation. MAPK signaling is tightly regulated so that optimal biological activities are achieved and health is maintained. However, how the specificity of the signaling flow along each cascade is achieved is still relatively unclear. In this review, we summarize recent advances in understanding the regulation of MAPK cascades and the roles of MAP kinases and their regulators in development and in immune responses. PMID- 17726578 TI - Regulation of cancer-related gene expression by galectin-3 and the molecular mechanism of its nuclear import pathway. AB - Galectin-3 (Gal-3), a member of the beta-galactoside-binding gene family, distributes inside and outside the cell and has pleiotropic biological functions such as cell growth, cell adhesion, cell-cell interaction, and mRNA processing in a specific situation. In particular, Gal-3 in the nucleus plays a pivotal role in the regulation of cancer-related gene expression, including cyclin D1, TTF-1 and MUC2, presumably associated with tumor progression. Therefore, to understand the mechanism of nuclear import of Gal-3 is very significant and might be developed to the new approach for the cancer treatment. In this review, we focus on the role of Gal-3 in the nucleus and the molecular mechanism of nuclear import pathways of Gal-3, providing the hints for the inhibition of Gal-3 function. PMID- 17726579 TI - The Nedd4-like family of E3 ubiquitin ligases and cancer. AB - Accumulating evidence suggests that E3 ubiquitin ligases play important roles in cancer development. In this article, we provide a comprehensive summary of the roles of the Nedd4-like family of E3 ubiquitin ligases in human cancer. There are nine members of the Nedd4-like E3 family, all of which share a similar structure, including a C2 domain at the N-terminus, two to four WW domains in the middle of the protein, and a homologous to E6-AP COOH terminus domain at the C-terminus. The assertion that Nedd4-like E3s play a role in cancer is supported by the overexpression of Smurf2 in esophageal squamous cell carcinoma, WWP1 in prostate and breast cancer, Nedd4 in prostate and bladder cancer, and Smurf1 in pancreatic cancer. Because Nedd4-like E3s regulate ubiquitin-mediated trafficking, lysosomal or proteasomal degradation, and nuclear translocation of multiple proteins, they modulate important signaling pathways involved in tumorigenesis like TGFbeta, EGF, IGF, VEGF, SDF-1, and TNFalpha. Additionally, several Nedd4-like E3s directly regulate various cancer-related transcription factors from the Smad, p53, KLF, RUNX, and Jun families. Interestingly, multiple Nedd4-like E3s show ligase independent function. Furthermore, Nedd4-like E3s themselves are frequently regulated by phosphorylation, ubiquitination, translocation, and transcription in cancer cells. Because the regulation and biological output of these E3s is such a complex process, study of the role of these E3s in cancer development poses some challenges. However, understanding the oncogenic potential of these E3s may facilitate the identification and development of biomarkers and drug targets in human cancer. PMID- 17726580 TI - Bladder cancer angiogenesis and metastasis--translation from murine model to clinical trial. AB - In the majority of cases, death from bladder cancer results from metastatic disease. Understanding the closely linked mechanisms of invasion, metastasis and angiogenesis in bladder cancer has allowed us to develop new therapeutic strategies that harbor the promise of decisive improvements in patient survival. The essential link between cell based experiments and the translation of novel agents into human patients with bladder cancer is the animal model. With emphasis on the orthotopic xenograft model, this review outlines some key mechanisms relevant to angiogenesis and the development of metastasis in bladder cancer. We highlight especially pathways related to MMP-9, IL-8, VEGF and EGFR. Most commonly, expression patterns of these markers in patients have correlated to disease progression and patient survival, which has led to laboratory investigations of these markers and eventually novel targeted therapies that are translated back into the clinic by means of clinical trials. Although imperfect in their translatability into clinical efficacy, animal models remain a critical tool in bladder cancer research. PMID- 17726582 TI - Successful endovascular treatment of a ruptured mycotic intracavernous carotid artery aneurysm in an AIDS patient. AB - INTRODUCTION: As the medical treatment for human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) continues to advance, the HIV related aneurysms may pose a clinical problem of increasing magnitude. The authors report on a successfully treated ruptured mycotic intracavernous carotid artery aneurysm case in an AIDS patient. METHODS: This 41-year-old AIDS patient presented with severe epistaxis. His head CT revealed acute blood in the left sphenoid sinus with bony erosion of the lateral wall (Fig. 1). The cerebral angiogram demonstrated a quite irregularly shaped intracavernous carotid artery aneurysm with proximal arterial stenosis (Fig. 2). RESULTS: After balloon test occlusion, this aneurysm was trapped endovascularly with detachable balloons (Fig. 3). The blood culture was positive for Aspergillus. The patient died 2 years later from other AIDS-related causes. CONCLUSION: The cerebral aneurysms in HIV/AIDS patients can be generally categorized into two groups: the mycotic aneurysms from bacterial or fungal infections and the HIV-associated aneurysms as a distinct entity. To plan appropriate interventions, a high degree of clinical suspicion must be exercised to promptly recognize the mycotic nature of many HIV related aneurysms. PMID- 17726581 TI - Smoking during pregnancy according to obstetric complications and parity: results of the EUROPOP study. AB - This study aimed to analyse the relationship between smoking and preterm birth (22-36 weeks) according to the main obstetric complications leading to the preterm birth, both overall and by parity. The EUROPOP study is a case-control study carried out between 1994 and 1997; 3,787 preterm and 5,602 full-term births were included, from maternity units in 10 countries, using the same protocol. Social, demographic and medical information was collected after delivery, from obstetric records and interviews with the mothers. Cases were classified according to the main obstetric complication (hypertension, haemorrhage, preterm premature rupture of membranes (PPROM), idiopathic spontaneous preterm labour, intrauterine growth retardation, all other causes). Multiple logistic regression analysis was used to control for confounders. Twenty four percent of cases and 20% of controls were smokers. Smoking during pregnancy, heavy smoking (>or=10 cigarettes per day) in particular, was a risk factor for preterm birth (aOR = 1.39, 95% CI:1.20-1.60). Smoking increased the risk of preterm delivery due to all obstetric complications other than hypertension. For these complications, the risk of preterm delivery associated with smoking was higher for multiparae (aOR = 1.46, 95% CI:1.24-1.71) than for primiparae (aOR = 1.18, 95% CI:1.00-1.38). In conclusion, smoking during pregnancy increases the risk of preterm birth among women with all obstetric complications except hypertension. This association is stronger in multiparae than in primiparae and the risk is higher for heavy smokers. PMID- 17726583 TI - Subarachnoid hemorrhage as a presentation of basilar artery dissection. AB - INTRODUCTION: Subarachnoid hemorrhages caused by intracranial dissections are rare. The management of dissections in these cases not clear. METHODS: Case report. RESULTS: An 82-year-old woman presented with acute drowsiness and vomiting. CT scan demonstrated extensive subarachnoid hemorrhage and hydrocephalus that subsequently required placement of ventriculoperitoneal shunt. Angiography revealed extensive basilar artery dissection and no aneurysms. The dissection did not produce a critical stenosis and, taking into consideration that the patient had a previous occlusion of her distal left vertebral artery, it was decided to manage the patient conservatively. On a 3-month follow-up, the patient was free of recurrent events. CONCLUSION: Basilar artery dissection can present with subarachnoid hemorrhage. No guidelines are available for management of basilar artery dissections and treatment should be tailored to the individual patient. PMID- 17726584 TI - Software sensors for fermentation processes. AB - Four software sensors based on standard on-line data from fermentation processes and simple mathematical models were used to monitor a number of state variables in Escherichia coli fed-batch processes: the biomass concentration, the specific growth rate, the oxygen transfer capacity of the bioreactor, and the new R(O/S) sensor which is the ratio between oxygen and energy substrate consumption. The R(O/S) variable grows continuously in a fed-batch culture with constant glucose feed, which reflects the increasing maintenance demand at declining specific growth rate. The R(O/S) sensor also responded to rapid pH shift-downs reflecting the increasing demand for maintenance energy. It is suggested that this sensor may be used to monitor the extent of physiological stress that demands energy for survival. PMID- 17726585 TI - [Advanced Trauma Life Support. A training concept also for Europe]. AB - Advanced Trauma Life Support (ATLS) is a concept for rapid initial assessment and primary management of an injured patient, starting at the time of injury and continuing through initial assessment, lifesaving interventions, re-evaluation, stabilization and, when needed, transfer to a trauma centre. Despite some shortcomings, it is the only standardized concept for emergency room management, which is internationally accepted. Because of its simple and clear structure, it is flexible and can be universally integrated into existing emergency room algorithms under consideration of local, regional as well as national and international peculiarities in the sense of a "common language of trauma". Under these aspects ATLS also seems to be a valid concept for Europe. PMID- 17726586 TI - [Intra-articular ketamine after arthroscopic knee surgery. Optimisation of postoperative analgesia]. AB - BACKGROUND: Surgery of the knee can be very painful and sufficient postoperative pain treatment is often problematic. To optimize postoperative analgesia, application of local analgesics has been suggested. In the present study it was investigated whether intra-articular administration of ketamine reduces the level of pain after arthroscopic knee surgery. MATERIAL AND METHODS: A total of 68 patients undergoing arthroscopic knee surgery were randomized into 4 groups. At the end of surgery the following pharmaceuticals were administered: 10 ml 0.25% bupivacaine intra-articular (i.a.), 0.25 mg S-(+)-ketamine/kg body weight to 10 ml in 0.9% NaCl i.a., 0.25 mg S-(+)-ketamine/kg body weight intravenous (i.v.), and 10 ml 0.9% NaCl i.a. as placebo. Postoperative pain therapy was performed as i.v. patient controlled analgesia (PCA) with piritramide. Postoperative opioid consumption and pain intensity were assessed as the main criteria in the postoperative course. RESULTS: All 4 groups were comparable with respect to biometrical data. The scores of the visual analogue scale (VAS) showed a significantly (p<0.05) lower pain intensity in patients treated with ketamine i.a. or i.v. compared to the other groups. Shortly after surgery the highest reduction of pain was detected in the i.a. ketamine group compared to i.a. bupivacaine or placebo administration. The postoperative opioid consumption was always lowest in the i.a. ketamine group. A significant difference in piritramide consumption (p<0.05) was demonstrated in the first 20 min after operation in the i.a. ketamine group compared to the i.a. administration of placebo and bupivacaine. CONCLUSIONS: The i.a. application of ketamine after arthroscopic knee surgery leads to a significant decrease of postoperative analgesic demand and decreases patients' subjective level of pain compared to i.a. application of bupivacaine or placebo. Likewise, the i.v. application of ketamine is similarly effective but the effect is of shorter duration. PMID- 17726588 TI - [Adverse events and adverse event reporting systems]. AB - Knowledge about the incidence of errors in anaesthesia and intensive care is only rudimentary but it appears justified to assume that errors occur much more often than we all expect. One reason is most likely the complexity of our work. Errors may alter our patients' health and healing process, imply financial and legal personal and institutional threats and may reduce health workers' performances. The article summarizes several methods to identify errors within a health care system and strengthens the importance of error analysis to reduce its incidence. Results of an analysis should be published if they are of general interest. PMID- 17726589 TI - [Utilization rates and turnover times as indicators of OR workflow efficiency]. AB - BACKGROUND: In many hospitals operating room (OR) utilization rates and turnover times (the time from the end of the previous surgical procedure to the beginning of the next) are used as indicators of OR workflow inefficiency. However, there have been no detailed studies to determine whether these indicators really provide an adequate picture of avoidable wasting of time in the OR. METHODS: All relevant OR processes in a busy surgical suite with nine ORs were studied in detail over an 8-week period. Productive OR processes, and also reasons for unused times, were recorded by independent observers at 5-minute intervals; they were able to code for 10 different productive activities and 20 different reasons for unused time. Unused time in the OR, the OR utilization rate and the average perioperative turnover times were calculated for each day and a correlation analysis was performed. RESULTS: In all, 3,501 OR hours and 790 surgical cases were studied. Productive processes accounted for 85.7% of the total OR time; the unused times were times with no scheduled cases (7.7%) and waiting times that arose for many different reasons (6.6%). Correlation analysis showed that there was no close correlation between waiting time and OR utilization (Spearman's r(s) 0.104 and r(s) 0.233). The correlations between total unused time (r(s) 0.718 and r(s) 0.745) and time with no scheduled cases (r(s) 0.706 and r(s) 0.620) and utilization were more robust, but for any given OR utilization rate the range of corresponding unused time or time without scheduled cases per day was considerable. The correlation between waiting time and perioperative turnover times was negligible (r(s) 0.185 and r(s) 0.175). When different definitions of utilization rate or perioperative turnover were used the results obtained were virtually identical. CONCLUSIONS: Utilization rate and perioperative turnover time cannot be used as indicators of OR workflow efficiency, since they cannot identify the days during which avoidable waiting times occur. If the aim is to identify underused OR time and factors that hamper workflow efficiency, waiting times and times without scheduled cases need to be recorded directly and separately. PMID- 17726591 TI - [Liver resection: prt II. Operative procedure]. AB - Hepatic surgery has grown considerably in importance during the last two decades. Major roles in this development have been played by improvements in imaging diagnostics and intensive care and particularly advancements in general hepatic surgical techniques. We present the terminology of functional and segmental anatomy of the liver on which current hepatic surgery is based, along with operative strategies for standard, nonconventional, and repeat resections. Intraoperative complications are also discussed. PMID- 17726590 TI - [Nausea and vomiting in the postoperative phase. Expert- and evidence-based recommendations for prophylaxis and therapy]. AB - There are no consensus guidelines for the management of postoperative nausea and vomiting (PONV) in German speaking countries. This meeting was intended to develop such guidelines on which individual health care facilities can derive their specific standard operating procedures (SOPs). Anesthesiologists reviewed published literature on key topics which were subsequently discussed during two meetings. It was emphasized that recommendations were based on the best available evidence. The clinical relevance of individual risk factors should be viewed with caution since even well proven risk factors, such as the history of PONV, do not allow the identification of patients at risk for PONV with a satisfactory sensitivity or specificity. A more useful approach is the use of simplified risk scores which consider the presence of several risk factors simultaneously. Most individual antiemetic interventions for the prevention of PONV have comparable efficacy with a relative risk reduction of about 30%. This appears to be true for total intravenous anesthesia (TIVA) as well as for dexamethasone and other antiemetics; assuming a sufficiently high, adequate and equipotent dosage which should be weight-adjusted in children. As the relative risk reduction is context independent and similar between the interventions, the absolute risk reduction of prophylactic interventions is mainly dependent on the patient's individual baseline risk. Prophylaxis is thus rarely warranted in patients at low risk, generally needed in patients with a moderate risk and should include a multimodal approach in patients at high risk for PONV. Therapeutic interventions of PONV should be administered promptly using an antiemetic which has not been used before. The group suggests algorithms where prophylactic interventions are mainly dependent on the patient's risk for PONV. These algorithms should provide evidence-based guidelines allowing the development of SOPs/policies which take local circumstances into account. PMID- 17726592 TI - [Surgical concept and results of necrotizing fasciitis]. AB - BACKGROUND: Necrotizing fasciitis (NF) is still a source of high morbidity and mortality. These difficult cases are increasingly referred to burn centers due to special wound and critical care issues. Here we examine our institution's recent experience with a large series of NF. METHOD: We performed a retrospective chart review of 32 consecutive patients over a 10-year period with NF who required radical surgical debridement and surface reconstruction. RESULTS: Overall survival was 85%, with average length of stay of 74.0+/-7.5 days for survivors (S) and 68.8+/-6.3 days for nonsurvivors (NS) (P>0.05). Time until first operation was 5.2 days in S and 3.4 days in NS (P<0.05). Patient age averaged 51.1+/-11.2 years for S and 57.0+/-12.0 years for NS (P<0.05). Survivors averaged 1.6 relevant comorbidities and NS averaged 3.6 (P<0.05). Affected total body surface (TBS) per patient averaged 6.8+/-3.3% for S and 10.2+/-5.1% for NS (P<0.05). All NS had affection of the trunk, and none of the patients with exclusive affection of extremities died. CONCLUSIONS: There were frequent delays in diagnosis and referrals to our institution, and progress can be made in educating the medical community to identify these patients. Not only the affected TBS and location but also comorbidities, age, and immediate surgical treatment are important prognostic factors. Referral to a specialized facility such as a burn center is urgently recommended for optimal surgical intervention, wound care, and critical care management. PMID- 17726593 TI - [Trauma management under military conditions. A German field hospital in Afghanistan in comparison with the National Trauma Registry]. AB - BACKGROUND: The German armed forces run a role-III field hospital in Kabul, Afghanistan. Emergency room (ER) management is of utmost importance as a link between pre- and in-hospital treatment. PATIENTS AND METHODS: Prospective data were acquired of all patients admitted to the ER over a 3-month period. The quality of ER management was tested using established audit filters and comparing the results with those of the National Trauma Registry. RESULTS: A total of 353 patients were admitted to the ER (48.4% trauma cases). Fifty-nine patients were major trauma cases, and the proportion of combat-related injury was 33.2%. In comparison to the National Trauma Registry, significant differences were observed regarding age (25.2 vs 41.7 years, P<0.0001) and injury severity (NISS 18.8 vs 28.8, P<0.0001). The demands on the quality of ER management have increased. Using the audit filters of the National Trauma Registry, significant differences were observed regarding ER management. CONCLUSION: In a military setting, medical treatment of major trauma victims is influenced by multiple adverse factors significantly affecting the quality of trauma management. PMID- 17726594 TI - [Gastrointestinal involvement in systemic sclerosis. An underestimated complication]. AB - Systemic sclerosis (SSc) belongs to the family of autoimmune connective tissue diseases and is still a challenge to every practicing physician. The disorder is characterized by progressing fibrosis of the skin and internal organs, abnormal activation of the immune system, and distinct changes in microcirculation. Although it is rare--with a prevalence of about 20:100000--patients need to be cared for in a daily setting. In general thickening of the skin is the first sign of the disease, so dermatologists are most frequently consulted first. Two subtypes exist, limited and diffuse forms. Both entities usually involve internal organs, and therefore interdisciplinary cooperation is mandatory. The increased morbidity and mortality depend predominantly on the grade of involvement of the affected organs. Therefore it is essential to diagnose systemic sclerosis early and to identify and monitor all complications closely. In this respect gastrointestinal involvement is frequently neglected, owing to its primarily non life-threatening character, resulting in substantially delayed therapy. PMID- 17726595 TI - [A 40-year-old female with headache and infarction ECG]. AB - Cerebral lesions may contribute to a transient left ventricular ballooning syndrome that can mimic acute myocardial infarction. Fibrinolytic therapy or GP IIb/IIIa antagonists should be withheld in cases of neurologic disorder or unconsciousness even in the presence of ST-elevation.ECG transmission by telemetry and myocardial infarction alarm networks allow correct diagnosis and catheter treatment within required time limits. PMID- 17726597 TI - [Penoscrotal elephantiasis: diagnostics and treatment options]. AB - Penoscrotal elephantiasis is a symptom that can be caused by local but also by systemic disorders. When the changes are reversible, conservative measures such as physical and antiphlogistic approaches lead to success. In cases of irreversible penoscrotal elephantiasis, excision and amputation of the affected penoscrotal areas are recommended to eliminate the functional disturbances. In all manifestations it is important to prevent and treat those diseases known to cause elephantiasis. PMID- 17726596 TI - [68-year-old female patient with dyspnea and hypokalemic hypertension]. AB - Ectopic ACTH syndrome is a rare differential diagnosis of hypokalemic hypertension. Patients with ectopic ACTH syndrome due to small cell lung cancer have a poor prognosis. We report on a 68-year-old female patient who presented with dyspnea and hypokalemic hypertension. Endocrine testing was consistent with ectopic ACTH syndrome due to small cell lung cancer. After initiation of chemotherapy with etoposide and carboplatin ACTH and cortisol levels normalized and clinical symptoms impressively improved. PMID- 17726598 TI - QTL analysis of resistance to Fusarium head blight in the novel wheat germplasm CJ 9306. II. Resistance to deoxynivalenol accumulation and grain yield loss. AB - Fusarium head blight (FHB or scab) caused by Fusarium species is a destructive disease in wheat, not only causing dramatic decrease of grain yield and quality, but also leading to serious mycotoxin contamination in the infected grains. This study was conducted to identify and quantify quantitative trait loci (QTLs) contributing to resistance to deoxynivalenol (DON) accumulation as well as to grain yield loss in a population of 152 F(7) recombinant inbred lines (RILs) derived from the cross Veery/CJ 9306. DON content in scabby grains and relative decreases of yield components were analyzed. Two new QTLs (QFhs.nau-2DL and QFhs.nau-1AS) for resistance to DON accumulation caused by FHB in wheat were detected, and QTLs QFhs.ndsu-3BS and QFhs.nau-5AS were also validated in CJ 9306, based on a constructed genetic linkage map. On the average of three experiments, major QTLs QFhs.ndsu-3BS and QFhs.nau-2DL explained up to 23 and 20% of phenotypic variation, respectively. QFhs.nau-1AS and QFhs.nau-5AS separately explained 4-6% of phenotypic variation. The differences among years/experiments were significant for all the four QTLs. However, the QTL x environment interaction was significant only for QFhs.nau-2DL, but not for the others. The results suggest that simple sequence repeat (SSR) markers Xgwm533b associated with QFhs.ndsu-3BS, and Xgwm539 associated with QFhs.nau-2DL could be used in marker-assisted selection to enhance resistance to DON accumulation. QFhs.ndsu 3BS + QFhs.nau-2DL and QFhs.nau-2DL + QFhs.nau-5AS would be the optimum choices for two-locus combinations. QFhs.ndsu-3BS was also validated in CJ 9306 for resistance to grain yield loss, explaining 8-15% of phenotypic variation. No QTLs for resistance to DON accumulation or grain yield loss independent of Type II resistance were found. By comparison, however, either of QFhs.nau-2DL or QFhs.nau 5AS alone and their combination were more contributive to resistance to DON accumulation than to Type II resistance. PMID- 17726599 TI - Genetic diversity and population differentiation of traditional fonio millet (Digitaria spp.) landraces from different agro-ecological zones of West Africa. AB - Fonio millets (Digitaria exilis Stapf, D. iburua Stapf) are valuable indigenous staple food crops in West Africa. In order to investigate the genetic diversity and population differentiation in these millets, a total of 122 accessions from five countries (Benin, Burkina Faso, Guinea, Mali and Togo) were analysed by Amplified Fragment Length Polymorphisms (AFLPs). Genetic distance-based UPGMA clustering and principal coordinate analysis revealed a clear-cut differentiation between the two species and a clustering of D. exilis accessions in three major genetic groups fitting to their geographical origins. Shannon's diversity index detected in D. iburua was low (H = 0.02). In D. exilis, the most widespread cultivated species, moderate levels of genetic diversity (Shannon's diversity H = 0.267; Nei's gene diversity H' = 0.355) were detected. This genetic diversity is unequally distributed with the essential part observed in the Upper Niger River basin while a very low diversity is present in the Atacora mountain zone. Analysis of molecular variance (AMOVA) revealed that a large part of the genetic variation resides among the genetic groups (70%) and the country of origin (56%), indicating a clear genetic differentiation within D. exilis. Influence of mating system (inbreeding or apomixis), agricultural selection and ecological adaptations as well as founding effects in the genetic make-up of the landraces were visible and seemed to jointly contribute to the genetic structure detected in this species. The genetic variability found between the analysed accessions was weakly correlated with their phenotypic attributes. However, the genetic groups identified differed significantly in their mean performance for some agro morphologic traits. The results obtained are relevant for fonio millets breeding, conservation and management of their genetic resources in West Africa. PMID- 17726600 TI - Spontaneous patellar fracture in a soccer player occurred 3 years and 3 months after anterior cruciate ligament reconstruction with central third bone-patellar tendon-bone graft. PMID- 17726602 TI - Comparative performance study of different sample introduction techniques for rapid and precise selenium isotope ratio determination using multi-collector inductively coupled plasma mass spectrometry (MC-ICP/MS). AB - The analytical performance of five sample introduction systems, a cross flow nebulizer spray chamber, two different solvent desolvation systems, a multi-mode sample introduction system (MSIS), and a hydride generation (LI2) system were compared for the determination of Se isotope ratio measurements using multi collector inductively coupled plasma mass spectrometry (MC-ICP/MS). The optimal operating parameters for obtaining the highest Se signal-to-noise (S/N) ratios and isotope ratio precision for each sample introduction were determined. The hydride generation (LI2) system was identified as the most suitable sample introduction method yielding maximum sensitivity and precision for Se isotope ratio measurement. It provided five times higher S/N ratios for all Se isotopes compared to the MSIS, 20 times the S/N ratios of both desolvation units, and 100 times the S/N ratios produced by the conventional spray chamber sample introduction method. The internal precision achieved for the (78)Se/(82)Se ratio at 100 ng mL(-1) Se with the spray chamber, two desolvation, MSIS, and the LI2 systems coupled to MC-ICP/MS was 150, 125, 114, 13, and 7 ppm, respectively. Instrument mass bias factors (K) were calculated using an exponential law correction function. Among the five studied sample introduction systems the LI2 showed the lowest mass bias of -0.0265 and the desolvation system showed the largest bias with -0.0321. PMID- 17726603 TI - New concept for a toxicity assay based on multiple indexes from the wave shape of damped metabolic oscillation induced in living yeast cells (part I): characterization of the phenomenon. AB - The damped glycolytic oscillation phenomenon occurring in starved cells of the yeast Saccharomyces cerevisiae (NBRC 0565) was characterization for application to a toxicity bioassay. S. cerevisiae was grown under semi-anaerobic conditions. The transient oscillations were observed photometrically as the time course of the fluorescent intensity of reduced pyridine nucleotide resulting from instantaneous addition of glucose to a cell suspension. In this study, simple and reproducible conditions inducing damped oscillations were obtained by modifying a literature method. For estimation of the wave shapes of the damped oscillations we used six indexes. To investigate the total reproducibility as the averaged relative standard deviation (RSD(av)) for the six indexes obtained from the wave shapes, the damped oscillations were induced under the optimum conditions and the RSD(av) values were calculated as 14% in a buffer cell suspension (n = 62) and 22% in a water cell suspension (n = 78). Finally, the effects of glucose concentration on the six indexes were examined, and all the indexes changed when the glucose concentration was changed. Excellent correlations were obtained between the index of oscillation-state time and the concentration of glucose in a buffer cell suspension (r = 0.9985, 0.5-250 mmol L(-1), 10 points) and in a water cell suspension (r = 0.9989, 2.5 micromol L(-1)-250 mmol L(-1), 12 points), respectively. PMID- 17726604 TI - Visual guidance of landing behaviour when stepping down to a new level. AB - When stepping down from one level to another, the leading limb has to arrest downward momentum of the body and subsequently receive and safely support bodyweight before level walking can begin. Such step downs are performed over a wide range of heights and predicting when and where contact between the landing limb and the lower level will be made is likely a critical factor. To determine if visual feedback obtained after movement initiation is habitually used in guiding landing behaviour, the present study determined whether pre-landing kinematics and the mechanics of landing would be modulated according to the type of visual feedback available during the stepping down phase. Ten healthy participants (32.3 +/- 7.9 years) stepped, from a standing position, down from three different heights onto a forceplatform, either coming immediately to rest or proceeding directly to walking across the laboratory. Repeated trials were undertaken under habitual vision conditions or with vision blurred or occluded 2 3 s prior to movement initiation. Pre-landing kinematics were assessed by determining, for the instant of landing, lead-limb knee and ankle angle, stepping distance, forwards positioning of the body CM within the base of support and the forwards and downwards body CM velocity. Landing mechanics for the initial contact period were characterized using lead limb vertical loading and stiffness, and trail limb un-weighting. When vision was occluded movement time, ankle plantarflexion and knee flexion were significantly increased compared to that determined for habitual vision, whereas forwards body CM positioning and velocity, vertical loading and stiffness, and trail limb un-weighting, were significantly reduced (p < 0.05). Similar adaptations were observed under blurred conditions, although to a lesser extent. Most variables were significantly affected by stepping task and step height. Subjects likely reduced forwards CM position and velocity at instant of landing, in order to keep the CM well away from the anterior border of the base of support, presumably to ensure boundary margins of safety were high should landing occur sooner or later than expected. The accompanying increase in ankle plantarflexion at instant of landing, and increase in single limb support time, suggests that subjects tended to probe for the ground with their lead limb under modified vision conditions. They also had more bodyweight on the trail limb at the end of the initial contact period and as a consequence had a prolonged weight transfer time. These findings indicate that under blurred or occluded vision conditions subjects adopted a cautious strategy where by they 'sat back' on their trail limb and used their lead limb to probe for the ground. Hence, they did not fully commit to weight transfer until somatosensory feedback from the lead limb confirmed they had safely made contact. The effect of blurring vision was not identical to occluding vision, and led to several important differences between these conditions consistent with the use of impoverished visual information on depth. These findings indicate that online vision is customarily used to regulate landing behaviour when stepping down. PMID- 17726605 TI - The selective effect of the image of a hand on visuotactile interactions as assessed by performance on the crossmodal congruency task. AB - Seeing one's own body (either directly or indirectly) can influence visuotactile crossmodal interactions. Previously, it has been shown that even viewing a simple line drawing of a hand can also modulate such crossmodal interactions, as if viewing the picture of a hand somehow primes the representation of one's own hand. However, factors other than the sight of a symbolic picture of a hand may have modulated the crossmodal interactions reported in previous research. In the present study, we examined the crossmodal modulatory effects of viewing five different visual images (photograph of a hand, line drawing of a hand, line drawing of a car, an U-shape, and an ellipse) on tactile performance. Participants made speeded discrimination responses regarding the location of brief vibrotactile targets presented to either the tip or base of their left index finger, while trying to ignore visual distractors presented to either the left or right of central fixation. We compared the visuotactile congruency effects elicited when the five different visual images were presented superimposed over the visual distractors. Participants' tactile discrimination performance was modulated to a significantly greater extent by viewing the photograph of a hand than when viewing the outline drawing of a hand. No such crossmodal congruency effects were reported in any of the other conditions. These results therefore suggest that visuotactile interactions are specifically modulated by the image of the hand rather than just by any simple orientation cues that may be provided by the image of a hand. PMID- 17726606 TI - Priming of naive CD8+ T cells in the presence of IL-12 selectively enhances the survival of CD8+CD62Lhi cells and results in superior anti-tumor activity in a tolerogenic murine model. AB - During the antigen-dependant activation process several subsets CD8+ T cells appear with different phenotypic and functional characteristics. Recent studies indicate that the state of T cell differentiation radically affects their ability to effectively respond to tumor challenge, with early effector CD8+ T (CD62Lhigh) cells having better anti-tumor activity. Thus strategies aimed at optimizing the generation of such subpopulations could significantly enhance the effectiveness of adoptive cell therapy (ACT) for cancer. In this study, we show that priming of naive CD8+ T cells in the presence of IL-12 selectively rescued early CD8+ CD62L(hi) from activation induced cell death and resulted in the increased accumulation of this subset of CD8+ T cells. Furthermore, we demonstrated that IL 12 directly modulated the expression of CD62L on activated CD8+ T cells. When used for ACT, naive CD8+ T cells primed in vitro in the presence of IL-12 showed superior anti-tumor activity toward B16 melanoma. Importantly, using the Pmel-1 model, priming pmel-1 cells in vitro with IL-12 reduced the state of functional tolerance associated with the non-mutated "self" tumor antigen gp100, as demonstrated by significant tumor responses in the absence of vaccination. Together, our results suggest that in vitro conditioning of naive CD8+ T cells with IL-12 prior to ACT could significantly enhance their anti-tumor activity. PMID- 17726607 TI - Effects of tumor selective replication-competent herpes viruses in combination with gemcitabine on pancreatic cancer. AB - PURPOSE: Pancreatic cancer still has a poor prognosis, even if aggressive therapy is pursued. Currently, new modalities of oncolytic virus therapy are being tested against this cancer. The combination of one of two representative mutant herpes simplex viruses (R3616: gamma(1)34.5 inactivated, hrR3: UL39 inactivated) with a standard anti-pancreatic cancer chemotherapy drug (gemcitabine), was investigated in this study. EXPERIMENTAL DESIGN: The intracellular concentration of ribonucleotide reductase was estimated by Western blotting. The effect of gemcitabine on viral replication and the total cytotoxic effect of the combination therapy were investigated on pancreatic cancer cell lines. We compared the results of two oncolytic viruses, R3616 and hrR3. A mouse model of pancreatic cancer with peritoneal dissemination was used to evaluate the in vivo effect of the combination therapy. RESULTS: Although the replication of both viruses was inhibited by gemcitabine, the combination caused more tumor cell cytotoxicity than did virus alone in vitro. The results with R3616 were more striking. Although the difference was not statistically significant, R3616 with gemcitabine had a greater effect than did R3616 alone, while hrR3 with gemcitabine had a weaker effect than did hrR3 alone in vivo experiments. CONCLUSION: The combination of oncolytic virus with gemcitabine is a promising new strategy against advanced pancreatic cancer. Each virus has different functional characteristics, and can affect the results of the combination of viruses and chemotherapy drugs. The results indicate that there is a complicated interaction among viruses, cells, and chemotherapy drugs and that the best combination of oncolytic virus and chemotherapeutic agents should be studied more extensively before embarking on a clinical trial. PMID- 17726608 TI - [What to do in cases of inadequate effectiveness of botulinum toxin for the treatment of eyelid cramping?]. AB - In 5-15% of individuals suffering essential blepharospasm, treatment with botulinum toxin is insufficient. In these cases the following measures can be applied: increase the dose, increase or vary the injection sites, change the botulinum toxin medication, use additional oral medication, or perform surgery. Certain measures can also be carried out by the patient. In cases of hemifacial spasm, inadequate results of botulinum toxin injections are even more unusual. But for these cases, additional oral medication or the neurosurgical Janetta operation can be used. PMID- 17726610 TI - Bochdaleck diaphragmatic hernia, complicated by an antenatal gastric perforation, presenting as a pneumothorax and a perforative peritonitis. AB - The presentation of congenital diaphragmatic hernia (CDH) at birth may fall outside the typical features (cyanosis, tachypnea and respiratory failure), manifesting, instead, also with others pictures that make the diagnosis difficult or even impossible. We report a case of CDH presenting as a pneumothorax and a perforative peritonitis due to an antenatal gastric perforation. PMID- 17726611 TI - Effect of etanercept on insulin secretion and insulin sensitivity in a randomized trial with psoriatic patients at risk for developing type 2 diabetes mellitus. AB - Tumor necrosis factor-alpha (TNF-alpha) inhibitors have been used in the treatment of psoriasis, which is associated with the insulin resistance syndrome. The purpose of this study was to determine the effect of etanercept, a TNF-alpha inhibitor, on insulin secretion and insulin sensitivity in psoriatic patients with high risk factors to develop type 2 diabetes mellitus. Randomized double blind clinical trial with 2 weeks of follow-up. The allocation was done by simple randomization. The investigation was performed in 12 psoriatic patients with indication of systemic treatment and 2 or more risk factors for type 2 diabetes mellitus. Patients with infections, topical corticosteroids or salicylic acid ointments for 6 weeks before the study, diabetes, acromegaly, cancer and other systemic diseases were excluded. All subjects gave written informed consent to participate in the study and the protocol was approved by the hospital-based Ethical Committee. Etanercept was injected in a subcutaneous dose of 25 mg in 1 ml twice by week for 2 weeks or 1 ml of saline solution as placebo. Insulin secretion was estimated with the formula for the homeostasis model analysis beta cell function index and insulin sensitivity was assessed using the euglycemic hyperinsulinemic clamp technique. There was no significant difference in insulin secretion and insulin sensitivity with etanercept. Fasting serum insulin levels were decreased in the etanercept group (146 +/- 117-111 +/- 87 pmol/l, P = 0.04). Etanercept did not modify insulin secretion and insulin sensitivity in psoriatic patients with risk factors for type 2 diabetes mellitus. PMID- 17726612 TI - Microtubule breakage is not a major mechanism for resolving end-to-end chromosome fusions generated by telomere dysfunction during the early process of immortalization. AB - Telomeres, the terminal chromosomal structure crucial for maintaining genomic integrity, shorten with deoxyribonucleic acid replications in most human somatic cells. Chromosomes carrying critically short telomeres tend to form end-to-end fusions, which are subject to breakage during cell division. However, it remains obscure how such telomere-mediated fusions are resolved during the process of immortalization, which is an early and indispensable step toward cancer. It has been hypothesized that the breakage could occur at either the microtubule or chromatid, causing numerical or structural chromosome instability, respectively. In this paper, we show that although the distributions of chromosomal segment losses or gains involved in structural aberrations were significantly correlated with the profiles of critically short telomeres in human epithelial cells undergoing immortalization, no such association was detected for whole-chromosome losses or gains in either metaphase or interphase cells. By distinguishing between homologues, we further showed that the specific homologues with critically short telomeres and frequent end-to-end fusions were not preferentially involved in respective whole-chromosome losses or gains. Our data therefore demonstrate that microtubule breakage is not a major mechanism for resolving chromosomal end-to-end fusions in human cells undergoing immortalization. An important implication of this finding is that microtubule kinetochore attachment is stronger than the chromosome structure. PMID- 17726613 TI - Parotitis and acute pancreatitis in a patient with ulcerative colitis. AB - Ulcerative colitis (UC) has been associated with a number of extraintestinal manifestations, but an association with salivary gland involvement has never been reported. We describe a patient with UC who developed acute pancreatitis and parotitis. Some autoantibodies against common antigens presenting in both the parotid gland and the pancreas might have induced pancreatitis and parotitis in our patient with UC. PMID- 17726614 TI - Costello syndrome: clinical diagnosis in the first year of life. AB - We report on three patients with Costello syndrome (CS) diagnosed during the first year of life and try to outline the clinical characteristics facilitating early recognition of this syndrome, which can now be corroborated by testing the HRAS gene. Phenotypical overlap of CS with Noonan (NS) and cardiofaciocutaneous syndrome (CFCS), particularly in neonatal age, is well known. Diagnostic features useful for recognition of CS in the first year of life are the following: (1) fetal and neonatal macrosomia with subsequent slow growth due to severe feeding difficulties, (2) developmental delay, (3) particularly coarse facial dysmorphisms and gingival hyperplasia, (4) skeletal anomalies as osteoporosis and metaphyseal enlargement, (5) hypertrophic cardiomyopathy (HCM) with asymmetric septal thickening and systolic anterior motion of the mitral valve, and (6) specific atrial arrhythmias. Following a clinical suspect of CS based on specific features, molecular screening of HRAS gene mutations should precede analysis of the other genes in the Ras-MAPK pathway implicated in related disorders with overlapping phenotypes. PMID- 17726615 TI - Predictors of 6-minute walk test and 12-minute walk/run test in obese children and adolescents. AB - The purpose of this study was to identify predictors of the distance achieved during a 6-minute walk test and a 12-minute walk/run test (Cooper test) in obese children and adolescents and to evaluate the influence of a residential treatment on the association of these predictors with the distance. A search of the Revalidation Centre Zeepreventorium (De Haan, Belgium) medical records database of all children and adolescents (age 10 to 18 yrs) treated for obesity between September 2003 and February 2006, revealed 65 charts with all relevant data (anthropometrical, maximal graded exercise, lung function, 6-minute walk test and 12-minute walk/run test) at admission as well as after 3 months treatment. The multidisciplinary treatment has a positive influence on anthropometrical variables, endurance capacity, vital capacity, and residual volume (p < 0.05). The distance covered during the 6-minute walk test and the 12-minute walk/run test is correlated with all anthropometrical data and peak VO2 (p < 0.05). After 3 months of treatment, bivariate correlation was stronger for almost every parameter compared to admission. Following a stepwise regression, BMI z-score is a dominant predictor of both field tests at admission and after 3 months treatment. VO2peak contributes only significantly in the 12-minute walk/run test at admission. CONCLUSION: In obese children and adolescents BMI z-score is the most dominant predictor of the variability in performances on the 6-minute walk test and the 12-minute walk/run test at admission as well as after 3 months of treatment. PMID- 17726616 TI - Polymorphisms in methionine synthase (A2756G) and cystathionine beta-synthase (844ins68) and susceptibility to carcinomas of the upper gastrointestinal tract. AB - PURPOSE: Folate deficiency is considered to increase the risk for the development of malignant tumors such as prostate and colorectal cancer. Methionine synthase (MTR) and cystathionine ss-synthase (CBS) are enzymes that play a central role in folate metabolism, thereby affecting DNA methylation and synthesis. A single A- >G substitution at nucleotide 2756 of the MTR and a 68 bp CBS insertion polymorphism in exon 8 have been associated with decreased enzyme activity. The purpose of this study is to compare the association of the MTR A2756G polymorphism and CBS insertion polymorphism with susceptibility to carcinomas of the upper gastrointestinal tract. METHODS: Using the restriction fragment length polymorphism (RFLP)-PCR, the prevalence of MTR A2756G and CBS insertion polymorphism was determined in healthy controls (n = 257) and in patients with esophageal squamous cell carcinoma (ESCC) (n = 263), Barrett's esophagus associated esophageal adenocarcinoma (BC) (n = 89), cardiac carcinoma (CC) (n = 144), or gastric carcinoma (GC) (n = 221) from German Caucasian subjects. RESULTS: No significant difference in MTR A2756G genotype distribution was observed between controls (A/A 66.9%, A/G 29.8%, G/G 3.3%) and patients with ESCC (A/A 61.7%, A/G 36.3%, G/G 2.1%), BC (A/A 69.2%, A/G 26.9%, G/G 3.9%), CC (A/A 51.8%, A/G 44.6%, G/G 3.6%), or GC (A/A 73.4%, A/G 20.9%, G/G 5.7%). Similarly, the CBS genotype (I: allele with 68 bp insertion; N: allele without insertion) distribution among German patients with ESCC (N/N 86.8%, I/N 13.2%), BC (N/N 90.2%, I/N 9.8%), CC (N/N 90.1%, I/N 9.9%) or GC (N/N 91.3%, I/N 8.7%) was not different from healthy controls (N/N 90.4%, I/N 9.6%). The gene allele constellation I/I was not present. CONCLUSIONS: The current study suggests that there is no association between MTR A2756G polymorphism and the CBS (844ins68) insertion polymorphism and cancer of the upper gastrointestinal tract. PMID- 17726618 TI - Retrospective cohort study between selective and standard C3-7 laminoplasty. Minimum 2-year follow-up study. AB - A total of 64 patients with cervical spondylotic myelopathy (CSM) were assessed in this study. Forty-two patients underwent selective expansive open-door laminoplasty (ELAP). Twenty-two patients who underwent conventional C3-7 ELAP served as controls. There were no significant differences in recovery rate of JOA scores, C2-C7 angle or cervical range of motion between two groups. Incidence of axial symptoms and segmental motor paralysis in selective ELAP was significantly lower than those in the C3-7 ELAP. Size of anterior compression mass, postoperative spinal cord positions and decompression conditions were evaluated using preoperative or postoperative MRI in 50 of 64 patients. There was a positive correlation between number of expanded laminae and maximum anterior spaces of spinal cord. Incomplete decompression was developed in three of 37 patients in selective ELAP and in two of 13 patients in C3-7ELAP. Mean size of anterior compression mass at incomplete decompression levels was significantly greater than that at complete decompression levels. Since, there was less posterior movement of the spinal cord in selective ELAP than that in C3-7ELAP, minute concerns about size of anterior compression mass is necessary to decide the number of expanded laminae. Overall, selective ELAP was less invasive and useful in reducing axial symptoms and segmental motor paralysis. This new surgical strategy was effective in improving the surgical outcomes of CSM, and short-term results were satisfactory. PMID- 17726619 TI - Production of thermostable pectinase and xylanase for their potential application in bleaching of kraft pulp. AB - A very high level of alkalophilic and thermostable pectinase and xylanase has been produced from newly isolated strains of Bacillus subtilis and Bacillus pumilus respectively. Enzyme production for pectinase was carried out under SSF using combinations of cheap agricultural residues while xylanase was produced under submerged fermentation using wheat bran as substrate to minimize the cost of production of these enzymes Among the various substrates tested, the highest yield of pectinase production was observed by using combination of WB + CW (6592 U/g of dry substrate) supplemented with 4% yeast extract when incubated at 37 degrees C for 72 h using deionized water of pH 7.0 as moistening agent. The biobleaching effect of these cellulase free enzymes on kraft pulp was determined. Both xylanase and pectinase showed stability over a broad range of pH from 6 to 10 and temperature from 55 to 70 degrees C. The bleaching efficiency of the pectinase and xylanase on kraft pulp was maximum after 150 min at 60 degrees C using enzyme dosage of 5 IU/ml of each enzyme at 10% pulp consistency with about 16% reduction in kappa number and 84% reduction in permanganate number. Enzyme treated pulp when subjected to CDED(1)D(2) steps, 25% reduction in chlorine consumption and upto 19% reduction in consumption of chlorine dioxide was observed for obtaining the same %ISO brightness. Also an increase of 22 and 84% in whiteness and fluorescence respectively and a decrease of approximately 19% in the yellowness of the biotreated pulp were observed by pretreatment of the pulp with our enzymatic mixture. PMID- 17726617 TI - Effects of serine protease inhibitors on viability and morphology of Leishmania (Leishmania) amazonensis promastigotes. AB - To investigate the importance of serine proteases in Leishmania amazonensis promastigotes, we analyzed the effects of classical serine protease inhibitors and a Kunitz-type inhibitor, obtained from sea anemone Stichodactyla helianthus (ShPI-I), on the viability and morphology of parasites in culture. Classical inhibitors were selected on the basis of their ability to inhibit L. amazonensis serine proteases, previously described. The N-tosyl-L: -phenylalanine chloromethyl ketone (TPCK) and benzamidine (Bza) inhibitors, which are potential Leishmania proteases inhibitors, in all experimental conditions reduced the parasite viability, with regard to time dependence. On the other hand, N-tosyl lysine chloromethyl ketone (TLCK) did not significantly affect the parasite viability, as it was poor Leishmania enzymes inhibitor. Ultrastructural analysis demonstrated that both Bza and TPCK induced changes in the flagellar pocket region with membrane alteration, including bleb formation. However, TPCK effects were more pronounced than those of Bza in Leishmania flagellar pocket in plasma membrane, and intracellular vesicular bodies was visualized. ShPI-I proved to be a powerful inhibitor of L. amazonensis serine proteases and the parasite viability. The ultrastructural alterations caused by ShPI-I were more dramatic than those induced by the classical inhibitors. Vesiculation of the flagellar pocket membrane, the appearance of a cytoplasmic vesicle that resembles an autophagic vacuole, and alterations of promastigotes shape resulted. PMID- 17726620 TI - Antimicrobial susceptibility of Lactobacillus species isolated from commercial ethanol plants. AB - Bacterial contamination of commercial fermentation cultures is a common and costly problem to the fuel ethanol industry. Antimicrobials such as virginiamycin (VIR) and penicillin (PEN) are frequently used to control contamination but there are little data available on the susceptibility of bacterial contaminants to these agents. A survey of bacterial contaminants from a wet-mill ethanol plant with no history of using antibiotics and a dry-grind facility that periodically doses with VIR found that the majority of contaminants were species of Lactobacillus. Thirty-seven isolates of Lactobacillus species from the wet-mill and 42 isolates from the dry-grind facility were tested for antimicrobial susceptibility using broth dilution and agar dilution methods. In general, the Lactobacillus isolates from the dry-grind plant had higher minimum inhibitory concentrations (MICs) for the tested agents than the isolates from the wet-mill facility. The MIC(90) for VIR was 4 microg/ml for the dry-grind isolates versus 0.25 microg/ml for the wet-mill isolates; and for PEN, the MIC(90)'s were >8 and 2 microg/ml for the dry-grind and wet-mill isolates, respectively. Sixteen Lactobacillus isolates from the dry-grind plant but none from the wet-mill possessed vatE, a gene that encodes a streptogramin acetyltransferase associated with resistance to virginiamycin. Despite decreased susceptibility to virginiamycin, most dry-grind isolates had MICs lower than the maximal recommended application rate of 6 ppm. PMID- 17726621 TI - A kinetic study on the plasmid stability of three Lactococcus lactis strains. AB - The plasmid stability of three wild type Lactococcus lactis strains and their mutants was investigated at different incubation time and temperatures in two different media [M17 broth and reconstituted skim milk (RSM)]. The results showed that both incubation times and temperature are effective on plasmid loss. The plasmid profiles of wild type strains exhibited 8 to 9 distinct plasmid species with molecular weights from 2.1 to 24.0 kb. Lactose fermentation ability was found to be encoded by 22.2 (strain U70), 23.6 (strain U29) and 24.0 (strain U52) kb plasmids in the wild type strains, respectively. The stabilities of the plasmids were explained by applying a second-order polynomial modeling system. Reasonable fittings were obtained for the model and the adjusted regression coefficients (R ( 2 ) (adj)) were between 0.76 and 0.99 for the overall data. Overall, it was found that incubation time had the most profound effect on plasmid stability, with plasmid loss occurring after 72 h, while temperatures in the range of 15-40 degrees C also induced plasmid instability. PMID- 17726623 TI - Effects of biological and technical factors on brain and muscle cholinesterases in Nile tilapia, Oreochromis niloticus: implications for biomonitoring neurotoxic contaminations. AB - Influence of body length, body weight, gender, sexual maturity, and tissue storage on brain and muscle cholinesterases (ChE) in Nile tilapia was evaluated considering its potential use in biomonitoring neurotoxic contaminations in tropical environments. Results show that ChE activities in both tissues decreased significantly with increased total length (4-24.5 cm) or body weight (1-186 g) of the fish and the relationships were curvilinear. Comparisons of the slopes and elevations of the regression lines of the logarithmic ChE and body size relationships of males with those of females indicated that gender had no significant effect on the body size-specific ChE activities. Response of the ChE of sexually mature males to chlorpyrifos exposure was similar to that of females. Gonadal maturity stage of this fish does not seem to influence ChE activities. Storage of tissues at -80 degrees C for 28 days had no significant effect on ChE activities in the control fish and the fish exposed to carbofuran. However, a partial reactivation of brain ChE activities was observed in the fish exposed to carbosulfan after 28 days of storage. The results emphasize the importance of consideration of body size of the fish and storage time of the tissues in order to formulate accurate conclusions about the neurotoxic chemical exposure when ChE of the fish is used in biomonitoring programs. PMID- 17726622 TI - Excess mortality following hip fracture: the role of underlying health status. AB - We evaluated the long-term excess mortality associated with hip fracture, using prospectively collected data on pre-fracture health and function from a nationally representative sample of U.S. elders. Although mortality was elevated for the first six months following hip fracture, we found no evidence of long term excess mortality. INTRODUCTION: The long-term excess mortality associated with hip fracture remains controversial. METHODS: To assess the association between hip fracture and mortality, we used prospectively collected data on pre fracture health and function from a representative sample of U.S. elders in the Medicare Current Beneficiary Survey (MCBS) to perform survival analyses with time varying covariates. RESULTS: Among 25,178 MCBS participants followed for a median duration of 3.8 years, 730 sustained a hip fracture during follow-up. Both early (within 6 months) and subsequent mortality showed significant elevations in models adjusted only for age, sex and race. With additional adjustment for pre fracture health status, functional impairments, comorbid conditions and socioeconomic status, however, increased mortality was limited to the first six months after fracture (hazard ratio [HR]: 6.28, 95% CI: 4.82, 8.19). No increased mortality was evident during subsequent follow-up (HR: 1.04, 95% CI: 0.88, 1.23). Hip-fracture-attributable population mortality ranged from 0.5% at age 65 among men to 6% at age 85 among women. CONCLUSIONS: Hip fracture was associated with substantially increased mortality, but much of the short-term risk and all of the long-term risk was explained by the greater frailty of those experiencing hip fracture. PMID- 17726624 TI - Successful femoral vessel puncture facilitated by using a J-tipped hydrophilic guidewire in pediatric cardiac catheterization. AB - Vascular access is an important part of cardiac catheterization, but it is extremely difficult in some cases. We present two cases in which a J-tipped hydrophilic guidewire inserted from the contralateral vessel facilitated successful vascular access after initial access failure by conventional method using anatomical landmark. PMID- 17726625 TI - Transthoracic echo-Doppler assessment of coronary microvascular function late after Kawasaki disease. AB - The goal of this study was to demonstrate that Doppler transthoracic echocardiography (TTE) may represent a valuable tool for the noninvasive demonstration of coronary microvascular dysfunction in children with previous Kawasaki disease (KD) by the measurement of coronary flow reserve (CFR) during cold pressor test (CPT). Twenty-five children with previous KD (mean follow-up, 4.6 +/- 2.6 years) were included in the study-16 with no evidence of coronary artery lesions (CALs(-)) by TTE and 9 with coronary aneurysms (CALs(+)). Seventeen age-matched healthy subjects were also recruited. Diastolic peak velocity was measured by pulsed Doppler both at rest (DPV(Rest)) and during CPT (DPV(CPT)) in the anterior descending artery. CFR was calculated as DPV(CPT)/DPV(Rest). KD patients demonstrated significantly higher values of DPV(Rest) (0.21 +/- 0.05 vs 0.13 +/- 0.01 cm/sec, p < 0.0001) and DPV(CPT) (0.33 +/- 0.07 vs 0.27 +/- 0.03 cm/sec, p < 0.005). CFR was reduced in KD compared to control subjects (1.5 +/- 0.4 vs 2.1 +/- 0.2, p < 0.0001). CFR was decreased in a similar manner in both CALs(+) patients (1.4 +/- 0.4, p = 0.002 vs controls) and CALs(-) patients (1.6 +/- 0.4, p < 0.0001 vs controls). Doppler TTE at rest and during CPT may represent a valuable modality for CFR evaluation in children with a history of KD. CFR is significantly reduced in KD patients independently of the presence of CALs. PMID- 17726626 TI - Assessing and mitigating the effects of windblown soil on rare and common vegetation. AB - Acting under the auspices of the US Endangered Species Act, we quantified wind erosion and its effects on rare and common plant species on a semi-arid military installation in Hawaii. Our goal was to develop management strategies, based on local data, to aid the conservation of rare and common indigenous plants and their habitats. We collected windblown soil coming off of roads and other disturbed soils to assess likely impacts to plants occurring at certain heights and distances from disturbed surfaces. We then subjected plants in a glasshouse to windblown dust treatments, designed from our field data to simulate erosion events, and evaluated the effect of these treatments on photosynthesis and survival. We also designed several field experiments to examine the in-situ effects of windblown soil and soil substrate on germination, growth rate, and survival of indigenous and nonindigenous plants. We conclude from these experiments that most direct effects of windblown soil to plants can be effectively mitigated by locating roads and training areas at least 40 m from sensitive plant habitats and through vegetation management to maintain at least 11% aerial cover on disturbed surfaces. Effects of soil type on germination, growth, and survival was species-specific, emphasizing the importance of species trials prior to, or during, rehabilitation efforts. PMID- 17726627 TI - Objective follow-up after laparoscopic repair of large type III hiatal hernia. Assessment of safety and durability. AB - BACKGROUND: Symptomatic results of laparoscopic repair of large type III hiatal hernias, with/without prosthetic mesh, are often excellent; however, a high recurrence rate is detected when objective radiological/endoscopic follow-up is performed. The use of mesh may reduce the incidence of postoperative hernia recurrence or wrap migration in the chest. METHODS: We retrospectively studied 54 patients (10 men, 44 women; median: age 64.5 years) with a diagnosis of large type III hiatal hernia (>1/3 stomach in the chest on x-ray) who underwent laparoscopic repair at our department from January 1992 to June 2005. Complications, recurrences, and symptomatic and objective (radiological/endoscopic) long-term outcome were evaluated. RESULTS: Nineteen patients had laparoscopic Nissen/Toupet fundoplication with simple suture; in 35 patients a double mesh was added. The median radiological/endoscopic follow-up was 64 months (interquartile range (IQR): 6-104) for the non-mesh group and 33 (IQR:12-61) for the mesh group (p = 0.26). Recurrences occurred in 11/54 (20%) patients: 8/19 (42.1%) without mesh and 3/35 (8.6%) with mesh (p = 0.01). The 3 recurrences in the mesh group all occurred < or =12 months postoperatively; 4/8 recurrences in the non-mesh group occurred > or =5 years after operation. On multivariate logistic regression analysis, only mesh absence significantly predicted hernia recurrence or wrap migration. DISCUSSION: Laparoscopic repair of large type III hiatal hernias is safe and effective. Short-term symptomatic results are excellent, but mid-term objective radiological/endoscopic evaluation reveals a high recurrence rate. Possible reasons for failure of a laparoscopic hiatal repair are tension or poor muscle tissue characteristics in the hiatus. The use of a mesh, either by reducing tension or reinforcing muscle at the hiatus, might be associated with a lower recurrence rate. Longer-term follow-up will be needed before definitive conclusions can be drawn, however. PMID- 17726628 TI - Specific antibiotic prophylaxis based on bile cultures is required to prevent postoperative infectious complications in pancreatoduodenectomy patients who have undergone preoperative biliary drainage. AB - BACKGROUND: Preoperative biliary drainage (PBD) is associated with bacterial contamination of bile, but the effects of PBD on morbidity after pancreatoduodenectomy remain controversial. The aim of this study was to characterize bile contamination to develop successful specific antibiotic prophylactic strategies for pancreatoduodenectomy. METHODS: Ninety-one consecutive patients who underwent pancreatoduodenectomy for periampullary tumor were prospectively evaluated. Prophylactic antibiotics were selected based on preoperative bile cultures. Bile cultures and postoperative complications were compared in 46 patients who underwent PBD (drainage group) versus 45 patients who did not (nondrainage group). RESULTS: The incidence of positive bile cultures was higher in the drainage group (78%) than in the nondrainage group (36%) (P < 0.001). In the drainage group, positive bile cultures were frequently polymicrobial (61%) and demonstrated resistance to several antibiotics, including cefazolin (83%), cefmetazole (72%), and cefpirome (64%). Overall morbidity (30% and 22%) and infectious morbidity (13% and 11%) did not differ significantly between the drainage and nondrainage groups, respectively. CONCLUSIONS: PBD had a notable influence on bile microbial contamination, including a higher rate of antibiotic resistance. Therefore, specific antibiotic prophylaxis based on bile culture is required for preventing infectious complications in pancreatoduodenectomy patients who undergo PBD. PMID- 17726629 TI - The sealing effect of a fibrin tissue patch on the esophageal perforation area in primary repair. AB - BACKGROUND: The aim of this study was to investigate the efficacy of the fibrin tissue patch and to analyze its use in patients with esophageal perforation. METHODS: We studied 28 patients who were diagnosed with esophageal perforation between January 1990 and January 2006 at Akdeniz University Hospital. Sixteen (57.14%) were male. The average age was 59 +/- 9 years. We performed surgery and primary repair reinforcement even if the diagnosis of esophageal perforation was late. RESULTS: Twenty-three (82.14%) perforations were the result of endoscopic instruments; spontaneous perforations occurred in three (10.71%) patients. Postoperative complication (Heller myotomy) caused perforation in one patient (3.57%) and blunt trauma in one patient (3.57%). Three (10.71%) patients had cervical perforation, and 25 (89.29%) patients had thoracic esophageal perforation. Twelve (42.86%) patients underwent emergency surgery (within the first 24 h). Ten (35.71%) patients underwent surgery within 48 h, and the remaining 6 (21.43%) underwent surgery after 48 h. Nine (32.14%) patients had primary repair, 7 (25%) had reinforcement of the primary repair with fibrin tissue patch, 7 (25%) had esophagectomy and gastric pull-up, and 2 (7.14%) had drainage and placement of metallic stents. In four patients of the nine who had primary repair, fistula complication was detected, whereas in only one of the seven who had reinforcement of the primary repair with fibrin tissue patch was a fistula detected. Three patients (10.71%), two of whom had Boerhaave's syndrome, died. CONCLUSIONS: Surgical primary repair with fibrin tissue patch is the most successful treatment option in the management of esophageal perforation. PMID- 17726630 TI - Liver volumetry plug and play: do it yourself with ImageJ. AB - BACKGROUND: A small remnant liver volume is an important risk factor for posthepatectomy liver failure and can be predicted accurately by computed tomography (CT) volumetry using radiologic image analysis software. Unfortunately, this software is expensive and usually requires support by a radiologist. ImageJ is a freely downloadable image analysis software package developed by the National Institute of Health (NIH) and brings liver volumetry to the surgeon's desktop. We aimed to assess the accuracy of ImageJ for hepatic CT volumetry. METHODS: ImageJ was downloaded from http://www.rsb.info.nih.gov/ij/ . Preoperative CT scans of 15 patients who underwent liver resection for colorectal cancer liver metastases were retrospectively analyzed. Scans were opened in ImageJ; and the liver, all metastases, and the intended parenchymal transection line were manually outlined on each slice. The area of each selected region, metastasis, resection specimen, and remnant liver was multiplied by the slice thickness to calculate volume. Volumes of virtual liver resection specimens measured with ImageJ were compared with specimen weights and calculated volumes obtained during pathology examination after resection. RESULTS: There was an excellent correlation between the volumes calculated with ImageJ and the actual measured weights of the resection specimens (r(2) = 0.98, p < 0.0001). The weight/volume ratio amounted to 0.88 +/- 0.04 (standard error) and was in agreement with our earlier findings using CT-linked radiologic software. CONCLUSION: ImageJ can be used for accurate hepatic CT volumetry on a personal computer. This application brings CT volumetry to the surgeon's desktop at no expense and is particularly useful in cases of tertiary referred patients, who already have a proper CT scan on CD-ROM from the referring institution. Most likely the discrepancy between volume and weight results from exsanguination of the liver after resection. PMID- 17726631 TI - Technical error during deployment leads to vena cava filter migration and massive pulmonary embolism. AB - The Gunther Tulip vena cava filter is a safe, effective, well-established device for pulmonary embolism prophylaxis. We report a patient in whom there was migration of the filter to the right atrium, 2 weeks after insertion, caused by a technical error during deployment. An attempt to retrieve the filter percutaneously failed, necessitating removal at open-heart surgery. The potential causes of migration are described and the lessons learned from this unusual case are outlined. PMID- 17726632 TI - Endovascular repair of a primary iliac-cecal fistula presenting with gastrointestinal hemorrhage. AB - We report a case of an arterio-enteric fistula between an external iliac artery aneurysm and otherwise healthy cecum, presenting with torrential hemorrhage per rectum in an 85-year-old patient. Whilst fistulization to the aorta and common iliac arteries has been reported, to our knowledge no previous cases of primary fistulization between an external iliac aneurysm and normal cecum have been. Successful endovascular exclusion of the aneurysm was undertaken with a Wallgraft covered stent and the patient remains well at 1 year. PMID- 17726633 TI - Microarray analysis of gene expression of mouse hepatocytes of different ploidy. AB - Polyploidisation in hepatocytes has been associated with many physiologic and pathologic processes such as proliferation, metabolism, regeneration, aging, and cancer. We studied gene expression patterns in hepatocytes of different ploidy. Primary hepatocytes were obtained from mice of different ages: young (4-6 weeks old), adult (8-10 weeks old), and older (22-24 weeks old). Diploid (2N), tetraploid (4N), and octoploid (8N) hepatocytes were isolated for studies using a high-density mouse genome microarray. No major changes of gene expression patterns between hepatocytes of different ploidy were found. Fifty genes were identified as differentially expressed in the diploid and tetraploid populations, but the changes were less than twofold either way. Four genes (Gas2, Igfbp2, Nr1i3, and Ccne2) were differentially expressed in tetraploid and octoploid cells. This was confirmed in two age groups, "adult" and "older," but once again the factors were less than twofold and the expressions of Gas2 and Igfbp2 were more different between age groups than between ploidy classes. Our results show that polyploid hepatocytes are stable and "normal" without aberrant gene expression, unlike what is thought for cancer cells. By contrast to megakaryocytes, hepatocyte polyploidisation is not a differentiation step associated with major changes in gene expression. Our data support the hypothesis that hepatocyte polyploidisation is a protective mechanism against oxidative stress that occurs via a controlled process throughout growth and aging where binucleation is important. PMID- 17726634 TI - High frequency of chromosome 14 deletion in early-onset colon cancer. AB - PURPOSE: Several genes have been recognized, when mutated in the germline, to highly predispose to colorectal cancer, impairing the DNA mismatch repair system in hereditary nonpolyposis colon cancer syndrome, or APC/MYH in adenomatous polyposis. However, 10 percent of microsatellite stable colorectal cancer is reported to develop in an unexplained context of genetic predisposition. This study was designed to depict the genetic mechanisms underlying early-onset microsatellite stable colon cancers. METHODS: Patients younger than aged 50 years undergoing primary surgical resection for colon carcinoma were collected prospectively between 1993 and 2003. A first series of 8 samples has been allelotyped using 361 poly-CA polymorphisms distributed on the 39 autosomal arms within a larger set of 166 sporadic tumors. Genotyping of 24 poly-CA polymorphisms distributed on the 8 chromosomes exhibiting allelic losses in more than 30 percent of the previous cases was then applied to an independent series of 40 tumors. A third series of 70 tumors has been genotyped on chromosome 14 only. RESULTS: Comparison of genomic profile from patients younger and older than aged 50 years at the 8 most frequently lost chromosomes allowed, identify chromosome 14 as showing a significant difference between the two groups. Dense chromosome 14 genotyping detected two partial deletions in a general background of 57 percent allelic loss, pointing at a region located between D14S63 and D14S292. CONCLUSIONS: These observations suggest that a tumor-suppressor gene located on chromosome 14 might have an important role in microsatellite stable colon carcinogenesis. Because it seems to be more frequently involved in early onset cases, it could be a good candidate in inherited conditions. PMID- 17726635 TI - Cytoreductive surgery and perioperative intraperitoneal chemotherapy for colorectal carcinomatosis: if at first you don't succeed.... PMID- 17726636 TI - Physician beliefs regarding effectiveness of tobacco dependence treatments: results from the NJ Health Care Provider Tobacco Survey. AB - BACKGROUND: Physicians play an increasing role in tobacco dependence treatment as more prescription medications and community resources are developed. Beliefs about effectiveness can influence physicians' recommendations regarding treatment, so it is critical that these beliefs are evidence-based. OBJECTIVE: Describe physicians' beliefs regarding effectiveness of tobacco treatments. DESIGN: Self-reported, cross-sectional, mailed survey. PARTICIPANTS: 336 primary care physicians in New Jersey (60.3% response). MEASUREMENTS: Demographics, previous tobacco dependence training, awareness of guidelines, and perceived effectiveness of treatments. RESULTS: Physicians believed combination medications and bupropion to be the most effective (89 and 88% reported somewhat or very effective, respectively) and nicotine nasal spray least effective (50%). For nonpharmacologic treatments, physicians believed behavioral counseling (69%) and programs including group treatment (67%) were most effective, whereas telephone counseling (25%) and internet-based treatment (23%) were the least. Female and non-U.S.-trained physicians generally believed treatments to be more effective. CONCLUSIONS: Physicians in this sample believed that most cessation medications available and behavioral and group-based counseling are effective, which is supported by current evidence in the field. Low perceived effectiveness of telephone and internet treatments could hinder their utilization. Perceived effectiveness may affect physician recommendations. Therefore, training efforts to influence these beliefs warrant further attention. PMID- 17726637 TI - Complete nucleotide sequence of a Japanese isolate of Chrysanthemum virus B (genus Carlavirus). AB - The complete nucleotide sequence of a Chrysanthemum virus B isolate from Japan (CVB-S) has been determined. The genomic RNA of CVB-S is 8,990 nucleotides long, excluding the poly(A) tail and, like that of other carlaviruses, contains six open reading frames (ORFs). Multiple alignment and phylogenetic analyses indicated that the phylogenetic relationship among members of the genus Carlavirus is very diverse, with phlox virus S being the closest relative of CVB. In aphid transmission tests, CVB-S was transmitted at a very low rate by Aphis gossypii, a new vector of the virus. PMID- 17726638 TI - Beta-lactoglobulin as source of bioactive peptides. AB - Beta-lactoglobulin (beta-Lg) is currently an important source of biologically active peptides. These peptides are inactive within the sequence of the precursor protein, but they can be released by in vivo or in vitro enzymatic proteolysis. Once released, these peptides play important roles in the human health, including antihypertensive, antioxidant and antimicrobial activities as well as opioid-like features and ability to decrease the body-cholesterol levels. Bioactive peptides derived from beta-Lg are currently a point of intensive research. Their structure, biological significance and mechanism of action are briefly presented and discussed in this review. PMID- 17726639 TI - Correlation of in vitro and in vivo models for the oral absorption of peptide drugs. AB - The aim of this study was to evaluate two in vitro models, Caco-2 monolayer and rat intestinal mucosa, regarding their linear correlation with in vivo bioavailability data of therapeutic peptide drugs after oral administration in rat and human. Furthermore the impact of molecular mass (Mm) of the according peptides on their permeability was evaluated. Transport experiments with commercially available water soluble peptide drugs were conducted using Caco-2 cell monolayer grown on transwell filter membranes and with freshly excised rat intestinal mucosa mounted in Using type chambers. Apparent permeability coefficients (P (app)) were calculated and compared with in vivo data derived from the literature. It was shown that, besides a few exceptions, the Mm of peptides linearly correlates with permeability across rat intestinal mucosa (R (2) = 0.86; y = -196.22x + 1354.24), with rat oral bioavailability (R (2) = 0.64; y = -401.90x + 1268.86) as well as with human oral bioavailability (R (2) = 0.91; y = -359.43x + 1103.83). Furthermore it was shown that P (app) values of investigated hydrophilic peptides across Caco-2 monolayer displayed lower permeability than across rat intestinal mucosa. A correlation between P (app) values across rat intestinal mucosa and in vivo oral bioavailability in human (R (2) = 0.98; y = 2.11x + 0.34) attests the rat in vitro model to be a very useful prediction model for human oral bioavailability of hydrophilic peptide drugs. Presented correlations encourage the use of the rat in vitro model for the prediction of human oral bioavailabilities of hydrophilic peptide drugs. PMID- 17726642 TI - A normal birth following preimplantation genetic diagnosis by FISH determination in the carriers of der(15)t(Y;15)(Yq12;15p11) translocations: two case reports. AB - PURPOSE: To investigate the clinical application of fluorescence in situ hybridization (FISH) for assessing chromosome disorders of embryos in preimplantation diagnosis of carriers with der(15)t(Y;15)(q12;p11) translocations. METHODS: Multicolor FISH was performed using directly-labelled DNA probes, chromosome X with one (DXZ1, Xp11.1-q11.1), but Y with two (DYZ3, Yp11.1-q11.1 and DYZ1, Yq12). Normal embryos were transferred on day 6 at blastocyst stage. RESULTS: Couple A: Three of 6 biopsied embryos were normal. Two normal blastocysts were transferred, but no pregnancy was achieved. Couple B: Three of 6 biopsied embryos were normal. Two normal blastocysts were transferred. A normal male infant weighing 3,230 g was born by cesarean section on the 39th week of gestation. All of the remaining nonreplaced embryos showed mosaic or der(15). CONCLUSION: Embryos from carries of der(15)t(Y;15)(q12;p11) translocation showed a high frequency of chromosome abnormalities. PGD is a valuable screen tool for those couples to treat their infertility and break the transmission of der(15) chromosome for their offspring. PMID- 17726640 TI - Suicidal ideation in pregnancy: assessment and clinical implications. AB - The objectives of this study were 1) to determine the prevalence of suicidal ideation (SI) in pregnant women with a history of neuropsychiatric illness, 2) to assess the relative sensitivity of commonly used depression rating scales for detecting SI, and 3) to examine the sociodemographic and clinical predictors of SI in pregnant women. Demographic data, Beck Depression Inventory [BDI] and Hamilton Rating Scale for Depression [HRSD] questionnaires, and SCID interviews were obtained from 383 pregnant women presenting to the Emory Women's Mental Health Program or the Emory Women's Epilepsy Program. Among those who completed both scales, 29.2% endorsed SI on the BDI and 16.9% on the HRSD, with 33.0% endorsing SI on at least one of the rating scales and 13.1% on both rating scales. The rate of SI endorsement on the BDI was 73.3% higher than the HRSD. Multivariate logistic regression demonstrated that SI in pregnant women was associated with unplanned pregnancy (OR = 2.97), current major depression (OR = 4.12), and comorbid anxiety disorder (OR = 4.17). Further studies are warranted to identify additional predictors of perinatal suicidality and to clarify the nature of the association between such factors and the presence of SI in pregnant women. PMID- 17726643 TI - Mitochondria transfer can enhance the murine embryo development. AB - PURPOSE: To evaluate the effect of mitochondrial transfer on embryonic development. MATERIALS AND METHODS: Mitochondria concentrates were collected from murine hepatocytes and fertilized murine zygotes from young and older mice in the 2PN stage were subjected to mitochondrial transfer and cultured in vitro to evaluate the embryonic development. RESULTS: After extended in vitro culture, 37.65% and 20.91% embryos from the young mice developed to the blastocyst stage in the injected and control groups respectively, which is statistically significant. There was no difference in terms of hatching rates (1.76% and 1.82% respectively). Zygotes from the older mice (>20 weeks old) that received mitochondrial transfer also had a better developmental outcome than the control group (54.35% and 18.92% developed to morula stage, 43.48% and 8.11% developed to the blastocyst stage respectively), which is statistically significant. CONCLUSIONS: Our results for the murine model provide direct scientific evidence that mitochondrial transfer improves embryonic development. However, potential risks such as mitochondrial heteroplasmy, nuclear-mitochondrial interaction and epigenetic aspects all deserve further evaluation before mitochondrial transfer is applied clinically. PMID- 17726644 TI - Glutamate uptake is reduced in prefrontal cortex in Huntington's disease. AB - Huntington's disease (HD) is caused by a CAG repeat expansion in the HD gene, but how this mutation causes neuronal dysfunction and degeneration is unclear. Inhibition of glutamate uptake, which could cause excessive stimulation of glutamate receptors, has been found in animals carrying very long CAG repeats in the HD gene. In seven HD patients with moderate CAG expansions (40-52), repeat expansion and HD grade at autopsy were strongly correlated (r=0.88, p=0.0002). Uptake of [(3)H]glutamate was reduced by 43% in prefrontal cortex, but the level of synaptic (synaptophysin, AMPA receptors) and astrocytic markers (GFAP, glutamate transporter EAAT1) were unchanged. Glutamate uptake correlated inversely with CAG repeat expansion (r= -0.82, p=0.015). The reducing agent dithiothreitol improved glutamate uptake in controls, but not in HD brains, suggesting irreversible oxidation of glutamate transporters in HD. We conclude that impairment of glutamate uptake may contribute to neuronal dysfunction and degeneration in HD. PMID- 17726646 TI - Functional implications of caspase-mediated RhoGDI2 processing during apoptosis of HL60 and K562 leukemia cells. AB - RhoGDI2, a cytosolic regulator of Rho GTPase, is cleaved during apoptosis in a caspase-3 dependent fashion. By using 2D-gel electrophoresis, mass spectrometry and Western blotting we investigate in this paper the functional consequences of RhoGDI2 processing. We can show that loss of the N-terminal 19 amino acids results in a shift of the isoelectric point of the truncated RhoGDI2 (NDelta19) to a more basic value due to the removal of 9 acidic amino acids from the N terminus, which may be responsible for enhanced retention of the N-terminally truncated protein within the nuclear compartment. Fusion of the p53 nuclear export signaling sequence MFRELNEALELK to NDelta19 (NDelta19NES) abolished its apoptosis promoting properties, while overexpression of NDelta19 significantly increased the susceptibility to apoptosis induction by the proteasome inhibitor PSI and by staurosporine. These results suggest that cleavage of RhoGDI2 by caspase-3 is not a functionally irrelevant bystander effect of caspase activation during apoptosis, but rather expedites progression of the apoptotic process. PMID- 17726647 TI - The CD44 standard/ezrin complex regulates Fas-mediated apoptosis in Jurkat cells. AB - The transmembrane receptor CD44 conveys important signals from the extracellular microenvironment to the cytoplasm, a phenomena known as "outside-in" signaling. CD44 exists as several isoforms that result from alternative splicing, which differ only in the extracellular domain but yet exhibit different activities. CD44 is a binding partner for the membrane-cytoskeleton cross-linker protein ezrin. In this study, we demonstrate that only CD44 standard (CD44s) colocalizes and interacts with the actin cross-linkers ezrin and moesin using well characterized cell lines engineered to express different CD44 isoforms. Importantly, we also show that the association CD44s-ezrin-actin is an important modulator of Fas-mediated apoptosis. The results highlight a mechanism by which signals from the extracellular milieu regulate intracellular signaling activities involved in programmed cell death. PMID- 17726645 TI - Effect of glutamine synthesis inhibition with methionine sulfoximine on the nitric oxide-cyclic GMP pathway in the rat striatum treated acutely with ammonia: a microdialysis study. AB - Ammonia neurotoxicity is associated with overactivation of N-methyl-D-aspartate (NMDA) receptors leading to enhanced nitric oxide and cyclic GMP synthesis and to accumulation of reactive oxygen and nitrogen species. Ammonia is detoxified in the brain via synthesis of glutamine, which if accumulated in excess contributes to astrocytic swelling, mitochondrial dysfunction and cerebral edema. This study was aimed at testing the hypothesis that the activity of the NMDA/NO/cGMP pathway is controlled by the ammonia-induced production of Gln in the brain. Ammonium chloride (final concentration 5 mM), infused for 40 min to the rat striatum via a microdialysis probe, caused a significant increase in Gln (by 40%), NO oxidation products (nitrite+nitrate=NOx) (by 35%) and cGMP (by 50%) concentration in the microdialysate. A Gln synthetase inhibitor, methionine sulfoximine (MSO, 5 mM), added directly to the microdialysate, completely prevented ammonia-mediated production of Gln, and paradoxically, it increased ammonia-mediated production of NOx and cGMP by 230% and 250%, respectively. Of note, MSO given alone significantly reduced basal Gln concentration in the rat striatum, had no effect on the basal NOx concentration, and attenuated basal concentration of cGMP in the microdialysate by 50%. The results of the present study suggest that Gln, at physiological concentrations, may ameliorate excessive activation of the NO-cGMP pathway by neurotoxic concentrations of ammonia. However, in view of potential direct interference of MSO with the pathway, exogenously added Gln and less toxic modulators of Gln content and/or transport will have to be employed in further studies on the underlying mechanisms. PMID- 17726648 TI - A prospective study on dietary fat and incidence of prostate cancer (Malmo, Sweden). AB - OBJECTIVE: To study the associations between intake of various types of fat and risk of prostate cancer (PCa) in a population-based cohort. METHODS: We have studied 10,564 initially cancer-free men of the Malmo Diet and Cancer cohort, aged 45-73 years. Diet was assessed by a modified diet history method. Cases and clinical characteristics were ascertained via national and regional registry data. RESULTS: During a mean follow-up of 11.0 years, 817 incidental PCa cases were diagnosed. Out of these, 281 were classified as advanced. There were 202 cases occurring before 65 years of age. After adjustment for age and energy intake, there was no association between intake of any types of fat and risk of PCa, or between fat intake and advanced PCa or PCa occurring in persons aged <65 years. However, we observed positive associations between intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and risk of PCa. After adjustment for multiple confounders, the latter associations were weakened, but the results were otherwise virtually unchanged. CONCLUSIONS: This large study, with high-validity dietary data, does not support an association between intake of total, saturated, or mono-unsaturated fat and PCa risk. The observed associations between EPA/DHA intakes and PCa are difficult to interpret. PMID- 17726649 TI - Is Urografin density gradient centrifugation suitable to separate nonculturable cells from Escherichia coli populations? AB - The ability of Urografin or Percoll density gradient centrifugations to separate nonculturable subpopulations from heterogeneous Escherichia coli populations was analysed. Bacterial counts (total, active and culturable cells) and flow cytometric analyses were carried out in all recovered bands. After Urografin centrifugation, and despite the different origin of E. coli populations, a common pattern was obtained. High-density bands were formed mainly by nonculturable cells. However, the increase in cell density would not be common to all nonculturable cells, since part of this subpopulations banded in low-density zones, mixed with culturable cells. Bands obtained after Percoll centrifugation were heterogeneous and culturable and nonculturable cells were recovered along the gradient. Thus, fractionation in Urografin cannot be only attributed to changes in buoyant densities during the transition from culturable to nonculturable state. Urografin density gradients allow us to obtain enriched fractions in nonculturable subpopulations from a heterogeneous population, but working conditions should be carefully chosen to avoid Urografin toxicity. PMID- 17726650 TI - [Nephrology--fascinating relationships]. PMID- 17726651 TI - [Is the serum concentration of pentosidine a predictor of cardiovascular events in patients with type 2 diabetes and kidney disease?]. AB - BACKGROUND AND OBJECTIVE: Advanced glycation end-products (AGEs) are implicated in the pathogenesis of vascular damage of atherosclerosis, especially in diabetes and renal failure. Pentosidine, an AGE, is generated by glycation and oxidation reactions (glycoxidation product). METHODS: 218 patients at high risk of cardiovascular events (from the "Irbesartan in Diabetic Nephropathy Trial" [IDNT] cohort) with type 2 diabetes and nephropathy (mean age 61 +/- 6,4 years, 68 female, 150 male) were followed for a mean of 2.2 years. The mean GFR at baseline was 47,9 +/- 16,0 ml/min (MDRD formula). Serum levels of pentosidine were measured by high-performance liquid chromatography. The relationship between pentosidine, traditional risk factors and cardiovascular events (CVE) was tested in Cox proportional hazards models. RESULTS: The mean serum level of pentosidine at baseline was 148 +/- 113 pmol/ml, that of hemoglobin A (1c) (HbA (1c)) 8.6 +/- 1.7 %. During follow-up, 93 CVE occurred; a total of 50 patients died, 39 of cardiovascular causes. Final multivariate analysis showed low density lipoprotein (LDL) and duration of diabetes to be independent risk factors for a first cardiovascular event (including death from cardiovascular causes) (relative risk [RR] for the highest quartile compared with the lowest: LDL 3,041, confidence interval 1.616 - 5.724, P = 0.001; duration of diabetes: RR 2.629, CI 1.279 - 6.151, P = 0.011). CONCLUSION: The serum level of pentosidine was not an independent risk factor for cardiovascular outcomes in the selected cohort. This suggests that traditional risk factors may play a more important role in causing cardiovascular events and that serum levels of AGEs are of low predictive value. Further investigations are necessary to assess whether tissue levels of AGEs are of greater relevance. PMID- 17726652 TI - [Renal resistance index in patients with obstructive sleep apnea]. AB - BACKGROUND AND OBJECTIVE: Previous studies have demonstrated renal dysfunction in patients with obstructive sleep apnea (OSA). The renal resistance index (RI) measured by renal duplexsonography (RI = 1-[enddiastolic velocity/peak systolic velocity]) is at the same time a marker of parenchymal renal damage and predictor of the progression of renal dysfunction. It was the aim of this study to test the influence of OSA on RI. PATIENTS AND METHODS: RI was compared between patients with (n = 97) and those without OSA (n = 61). The impact of OSA on the RI was analysed by adjusting for age. Thus, the difference between the measured RI and the age-based RI was expressed as a percentage of the normal age-adjusted value (RI (%)). RESULTS: OSA patients showed a trend towards an increase in RI (69.1+/ 8.8 vs. 66.5+/-8.3 %, p = 0.068) and RI (%) (10.2+/-12.9 vs. 6.4+/-11.4 %, p = 0.060), respectively. In patients with mild or moderate OSA (apnea-hypopnea-index [AHI] 5 - 30/h) this difference was significant (RI: 70.5+/-9.1 vs. 66.5+/-8.2, p = 0.012; RI (%): 12.1+/-13,4 vs. 6.5+/-11.4 %, p = 0.012). RI of patients with severe OSA did not significantly differ from those without OSA. In patients with mild and moderate OSA there was a significant linear association between AHI and RI or RI (%). This association was independent of hypertension or diabetes. CONCLUSION: An impairment of renal perfusion and renal parenchymal damage due to increased sympathetic activity may promote renal dysfunction in patients with obstructive sleep apnea. PMID- 17726653 TI - [Is there a correlation between C-reactive protein and calcification inhibitors with cardiovascular parameters and risk factors in hemodialysis patients?]. AB - BACKGROUND AND OBJECTIVE: Patients on hemodialysis exhibit a drastically increased cardiovascular mortality. Inflammation, hyperphosphatemia and lack of calcification inhibitors are uremia-associated risk factors for vascular calcification. Functional and morphological vascular parameters are used to assess cardiovascular risk. The aim of our study was to analyse the relation between pulse wave velocity (PWV) and intima-media-thickness (IMT) with calcification inhibitors. METHODS: A cohort of 97 hemodialysis patients was consecutively selected and investigated (age 56 +/- 9 years). Carotid-femoral PWV, carotid IMT, left ventricular ejection fraction and septum thickness were determined. These parameters were correlated with serum levels of CRP and calcification inhibitors (fetuin-A and osteoprotegerin [OPG]). RESULTS: Both PWV and IMT showed a positive correlation with age and systolic blood pressure and a negative correlation with Kt/V (dialysis efficiency). Additionally, fetuin-A was negatively associated with CRP and positively with cholesterol and triglycerides. Serum levels of the calcification inhibitors fetuin-A and OPG were not correlated to PWV or IMT. CONCLUSION: The lack of correlation of calcification inhibitors with PWV and IMT means that functional and morphological measurements of vascular properties can not necessarily be replaced by analysing "biomarkers". PMID- 17726654 TI - [What is your diagnosis? Bilateral dacryoadenitis]. PMID- 17726655 TI - [Severe hyponatremia with pulmonary and cerebral edema in an Ironman triathlete]. AB - HISTORY AND ADMISSION FINDINGS: A 45-year-old female presented with somnolence and convulsions after finishing her first ironman triathlon. Besides the neurological symptoms she had a swollen face and swollen ankles. Rales could be heard on pulmonary auscultation. The past medical history was unremarkable. Due to musculoskeletal pain the patient had taken ibuprofen until two days before the race. INVESTIGATIONS: The laboratory tests showed severe hyponatremia ( 111 mmol/l ) and hypoosmolalitiy of the serum. The osmolality of the urine was high (314 mosm/kg). Radiological examination revealed pulmonary as well as cerebral edema. TREATMENT AND COURSE: On admission the patient was treated with hypertonic saline which increased the serum sodium concentration. Nevertheless she developed respiratory and hemodynamic failure. She had to be intubated, mechanically ventilated and needed catecholamines. After treatment with furosemide recovery occurred. The patient was extubated and was transferred to a hospital near her home without any neurolgical deficits one week after admission. One year later the former patient was again participant of the ironman triathlon. She was advised not to drink excessively and received oral salt supplementation. This time the athlete finished the race with a serum sodium concentration of 141 mmol/l. CONCLUSIONS: Ultra-endurance exercise can lead to severe hyponatremia, pulmonary and cerebral edema. This is caused mainly by fluid overload due to excesssive drinking and a release of ADH induced by hypovolemia and stress which impairs the excretion of free water. Hence a moderate fluid intake during and after endurance exercise is very important. PMID- 17726656 TI - [Postinterventional cholesterol crystal embolization]. AB - HISTORY AND ADMISSION FINDINGS: A 73-year old woman was admitted to the hospital because of progressive renal failure with onset 2 months after an angiogram of the legs. She had diabetes mellitus and was hypertensive. Her feet were cold, painful and showed irregular blue and purple discolorations. INVESTIGATIONS: Blood pressure was 170/80 mmHg, heart rate 72 bpm. Serum creatinine was 6,7 mg/dl (eGFR 7 ml/min) and she had proteinuria of 4,3 g/l. The erythrocyte sedimentation rate was markedly elevated, she had eosinophilia and hypocomplementemia. DIAGNOSIS AND THERAPY: Because of the acute renal failure and proteinuria a renal biopsy was taken, as well as a skin biopsy from the patients foot. Both biopsies showed cholesterol crystal emboli with elongated, biconvex transparent clefts and an inflammatory reaction of the vessel wall which had caused obstruction. Renal function did not recover, and the patient was transferred to the chronic dialysis program. Treatment with a statin was initiated and her blood pressure normalized. CONCLUSION: In most cases cholesterol crystal embolism is iatrogenic. This multiorgan syndrome occurs in patients at high risk of cardiovascular disease. Cholesterol crystals from ruptured atheromatous plaques become lodged in peripheral arteries and induce an obliterating inflammation of the vessel wall. Mortality is high (about 38 %). PMID- 17726657 TI - [What are the aims and targets of renal anemia therapy?]. PMID- 17726658 TI - [Differential diagnosis and therapy of pulmorenal syndrome--the nephrologist's perspective]. AB - The "pulmorenal syndrome" is a clinically defined syndrome under which one summarises disease entities with acute renal failure due to acute glomerulonephritis and alveolar lung hemorrhage. Wegener's granulomatosis, other inflammatory renal diseases and Goodpasture's syndrome are the most frequent causes of this syndrome. The physical examination and histological examination, mostly of a kidney biopsy, represent the mainstay of securing the diagnosis. The diagnosis is completed by serological testing for autoantibodies. The therapy is determined by the underlying disease. Plasmaspheresis is always performed when alveolar hemorrhage is present, and in most cases where the patient presents with the need for immediate dialysis. An immunosuppressive therapy is determined by the underlying disease. PMID- 17726659 TI - [Is it necessary to treat asymptomatic hyponatremia?]. PMID- 17726660 TI - Gas-phase basicity of methionine. AB - Proton affinity and protonation entropy of methionine (Met) were determined by the extended kinetic method from ESI-Q-TOF tandem mass spectrometry experiments. The values, PA(Met) = 937.5 +/- 2.9 kJ mol(-1) and Delta(p)S degrees (Met) = - 22 +/- 5 J mol(-1) K(-1), lead to gas-phase basicity GB(Met) = 898.2 +/- 3.2 kJ.mol( 1). Quantum chemical calculations using density functional theory confirm that the proton affinity of Met is indeed in the 940 kJ mol(-1) range and that a significant entropy loss, of at least - 25 J mol(-1) K(-1), occurs upon protonation. This last point is evidenced here for the first time and suggests revision of the tabulated protonation thermochemistry of Met. A comparison with previous experimental data allows us to propose the following evaluated thermochemical values: PA(Met) = 943 +/- 4 kJ mol(-1) and Delta(p)S degrees (Met) = - 35 +/- 15 J mol(-1) K(-1) and GB(Met) = 900 +/- 2 kJ mol(-1). PMID- 17726661 TI - Symptom severity and treatment course of bulimic patients with and without a borderline personality disorder. AB - There are contradictory results concerning the frequency of borderline personality disorder (BPD) in bulimic patients and its impact on eating pathology and treatment outcome. We evaluated 240 patients with bulimia nervosa using EDI 2, SIAB and SCL-90-R. Only a minority of patients had a BPD (13.8%). There were no differences in binging or purging behaviour between patients with and without BPD, but borderline patients had significantly more feelings of ineffectiveness and more disturbances in interoceptive awareness. Bulimic patients with BPD showed significantly more general psychopathology. Although, BPD patients started with higher levels of pathology, there were similar reductions of symptoms over the course of treatment in both groups. Psychotherapy in bulimic patients with a BPD has to focus not only on eating pathology but also on aspects that are caused by the severe personality disturbance. PMID- 17726662 TI - Targeting gold at the end of the rainbow: surgical gamma probes in the 21st century. AB - Surgical gamma detection probes (GDPs) have become important in the surgical management of neoplastic disease in the past 20 years. Their history and radiophysics are discussed, with consideration of the overarching issue of tumor to-background ratio (TBR). GDPs are currently most commonly used in sentinel node applications in a variety of tumors. Whether their role in clinical surgical practice can be extended to other applications will depend on the development of radiolabeled tumor marking agents which have much improved TBR, and parallel developments in oncology research which may overtake this technology. PMID- 17726663 TI - Radioimmunoguided surgery (RIGS), PET/CT image-guided surgery, and fluorescence image-guided surgery: past, present, and future. AB - (125)I-labeled anti-TAG-72 antibodies were applied in radioimmunoguided surgery (RIGS) to remove gross and occult tumors. It is challenging to handle (125)I labeled materials. PET/CT image-guided surgery utilizes (18)FDG to monitor the biochemical activity of the tumor and to integrate pre- and postoperative imaging for complete tumor removal. PET/CT image-guided surgery only detects later stage disease. Fluorescence image-guided surgery using anti-TAG-72 antibodies may provide opportunities for intraoperative cancer detection of both gross and occult tumors. PMID- 17726664 TI - Radio-guided surgery in neuroendocrine tumors. AB - The majority of Neuroendocrine tumors (NET) express somatostatin (SS) receptors, and thus can be successfully targeted with radiolabeled SS analogs in vivo. Somatostatin receptor scintigraphy (SRS) with (111)In-DTPA Octreotide is the main imaging technique for evaluation of NETs. Radio-guided surgery for NETs, therefore, primarily utilizes (111)In-DTPA Octreotide tumor localization mechanism and kinetics. Somatostatin analog radiopharmacy continues to evolve to include the development of more selective and higher affinity analogs and PET tracers. These changes are expected to open new venues for radio-guided surgery technology. PMID- 17726666 TI - Sentinel lymph node biopsy for gastrointestinal cancers. AB - Sentinel lymph node biopsy (SLNB) in gastrointestinal-(GI)-tract cancer is not yet of clinical relevance. Nevertheless, the results in the upper GI-tract promise to be helpful to individualize the indication for surgical therapy. SLNB in colon cancer still fails to show high validity to predict the nodal status, but may be helpful to clarify the prognostic role of micrometastases/isolated tumor cells. In anal cancer SLNB is able to guide the indication for groin irradiation. PMID- 17726665 TI - The sentinel concept in patients with cervical cancer. AB - The sentinel concept for patients with early cervical cancer has a high potential for decreasing morbidity and for increasing oncologic safety. The detection rate with technetium-labeling or a combination with blue dye varies between 84% and 92%. Sensitivity and negative predictive value depend on tumor size: the smaller the tumor, the higher the validity of the technique. Detection of circulating tumor cells in the sentinel node using HPVmRNA as marker may have a good prognostic value. Currently the sentinel concept should only be used in clinical studies before its validity has been proved. PMID- 17726667 TI - PET probe-guided surgery. AB - Intraoperative localization of PET-positive recurrent/metastatic lesions can be facilitated using a hand-held PET probe. PET probe is a high-energy gamma probe designed to process the 511 keV photons of PET tracers. Intraoperative gamma probe performance is a function of radiopharmaceutical uptake, clearance kinetics, and probe engineering, all determining the target to background ratio (TBR) and detection threshold. A minimum TBR of 1.5:1 is needed in the operative field for the operating surgeon to be comfortable the differences between tumor tissue and normal adjacent tissue are real. Due to high-energy photon fluxes, achieving a satisfactory TBR intraoperatively is challenging and requires development of a clinically feasible PET-probe guided surgery protocol. PMID- 17726668 TI - Characterization and expression profile of the ovarian cytochrome P-450 aromatase (cyp19A1) gene during thermolabile sex determination in pejerrey, Odontesthes bonariensis. AB - Cytochrome P450 aromatase (cyp19) is an enzyme that catalyzes the conversion of androgens to estrogens and may play a role in temperature-dependent sex determination (TSD) of reptiles, amphibians, and fishes. In this study, the ovarian P450 aromatase form (cyp19A1) of pejerrey Odontesthes bonariensis, a teleost with marked TSD, was cloned and its expression profile evaluated during gonadal differentiation at feminizing (17 degrees C, 100% females), mixed-sex producing (24 and 25 degrees C, 73.3 and 26.7% females, respectively), and masculinizing (29 degrees C, 0% females) temperatures. The deduced cyp19A1 amino acid sequence shared high identity (>77.8%) with that from other teleosts but had low identity (<61.8%) with brain forms (cyp19A2), including that of pejerrey itself. The tissue distribution analysis of cyp19A1 mRNA in adult fish revealed high expression in the ovary. Semi-quantitative reverse transcription polymerase chain reaction analysis of the bodies of larvae revealed that cyp19A1 expression increased before the appearance of the first histological signs of ovarian differentiation at the feminizing temperature but remained low at the masculinizing temperature. The expression levels at mixed-sex producing temperatures were bimodal rather than intermediate, showing low and high modal values similar to those at the feminizing and masculinizing temperatures, respectively. The population percentages of high and low expression levels at intermediate temperatures were proportional to the percentage of females and males, respectively, and high levels were first observed at about the time of sex differentiation of females. These results suggest that cyp19A1 is involved in the process of ovarian formation and possibly also in the TSD of pejerrey. PMID- 17726671 TI - Treatment choices, preferences and decision-making by patients with rheumatoid arthritis. AB - OBJECTIVES: To explore rheumatoid arthritis (RA) patient treatment preferences, their decision-making and the treatment choices they would make when faced with three anti-tumour necrosis factor-alpha (TNF-alpha) therapy options. METHODS: Two methods of enquiry were used: postal questionnaire and one-to-one interviews. RA patients not taking anti-TNF-alpha medications were asked to complete a questionnaire after reading a written scenario, which involved choosing and identifying factors that influenced their treatment choice from three anti-TNF alpha therapies: etanercept (Enbrel), adalimumab (Humira) and infliximab (Remicade). Patients who had tried more than one anti-TNF-alpha medication were asked at one-to-one interviews for their treatment preferences and how their current treatment had been decided. RESULTS: Both interviewees and questionnaire respondents chose adalimumab as their preferred treatment. Interviewees identified lack of control, convenience and technical issues as influencing treatment choice. Questionnaire respondents were less likely than interviewees to want to participate in making decisions about the selection of anti-TNF-alpha therapy. There were few gender differences. Patients younger than 61 years old were more confident about self-administering treatment, and preferred subcutaneous (sc) over intravenous (iv) medication, as this reduced regular hospital attendance. Older patients preferred health care staff to administer treatment and more readily identified 'contact with other patients/meeting others' and 'staff availability if problems arise' as factors influencing choice. CONCLUSIONS: RA patients demonstrate a clear treatment preference. Different factors influence patients who choose sc compared with iv medications. Many RA patients either wished to share in treatment decisions or relinquish responsibility to the health professional when choosing anti-TNF-alpha therapy. Patients require reassurance and continuing dialogue with clinicians to manage their condition optimally. PMID- 17726672 TI - A microarray strategy for mapping the substrate specificity of protein tyrosine phosphatase. PMID- 17726673 TI - Radicals in asymmetric organocatalysis. PMID- 17726674 TI - Structural integration of tellurium oxide into mixed-network-former glasses: connectivity distribution in the system NaPO(3)-TeO(2). AB - Sodium phosphate tellurite glasses in the system (NaPO(3))(x)(TeO(2))(1-) (x) were prepared and structurally characterized by thermal analysis, vibrational spectroscopy, X-ray photoelectron spectroscopy (XPS) and a variety of complementary solid-state nuclear magnetic resonance (NMR) techniques. Unlike the situation in other mixed-network-former glasses, the interaction between the two network formers tellurium oxide and phosphorus oxide produces no new structural units, and no sharing of the network modifier Na(2)O takes place. The glass structure can be regarded as a network of interlinked metaphosphate-type P(2) tetrahedral and TeO(4/2) antiprismatic units. The combined interpretation of the O 1s XPS data and the (31)P solid-state NMR spectra presents clear quantitative evidence for a nonstatistical connectivity distribution. Rather, the formation of homoatomic P--O--P and Te--O--Te linkages is favored over mixed P--O--Te connectivities. As a consequence of this chemical segregation effect, the spatial sodium distribution is not random, as also indicated by a detailed analysis of (31)P/(23)Na rotational echo double-resonance (REDOR) experiments. PMID- 17726675 TI - Host-extract induced changes in the secretome of the plant pathogenic bacterium Pectobacterium atrosepticum. AB - Pectobacterium atrosepticum is a Gram-negative plant pathogenic bacterium that causes rotting in potato stems and tubers. The secreted proteins of this pathogen were analyzed with proteomics from culture supernatant of cells grown in minimal medium supplemented with host extracts. More than 40 proteins were identified, among them known virulence determinants, such as pectic enzymes, metalloprotease, and virulence protein Svx, along with flagella proteins, GroEL and cyclophilin type chaperones and several hypothetical proteins or proteins with unknown function. Some of the identified proteins may be involved in utilization of nutrients or transport of minerals. Northern and real-time RT-PCR analyses suggested that most of the proteins upregulated by plant extract were transcriptionally regulated. Among the identified proteins were VgrG and four homologs of hemolysin-coregulated proteins (Hcps). A mutant strain lacking one of the hcp genes was not affected in virulence, while a bacterial strain overexpressing the same gene was shown to have increased virulence, which suggests that these proteins may be new virulence determinants of P. atrosepticum. Comparison of the secretomes of wild type cells and hrcC mutant defective in Type III secretion suggested that the production of the identified proteins was independent of functional Type III secretion system. PMID- 17726676 TI - Pixel-based analysis of multiple images for the identification of changes: a novel approach applied to unravel proteome patterns [corrected] of 2-D electrophoresis gel images. AB - A novel approach for revealing patterns of proteome variation among series of 2 DE gel images is presented. The approach utilises image alignment to ensure that each pixel represents the same information across all gels. Gel images are normalised, and background corrected, followed by unfolding of the images to 1-D pixel vectors and analysing pixel vectors by multivariate data modelling. Information resulting from the data analysis is refolded back to the image domain for visualisation and interpretation. The method is rapid and suitable for automatic routines applied after the gel alignment. The approach is compared with spot volume analysis to illustrate how this approach can solve persistent problems like mismatch of protein spots, erroneous missing values and failure to detect variation in overlapping proteins. The method may also detect variation in the border area of saturated proteins. The approach is given the name pixel-based analysis of multiple images for the identification of changes (PMC). The method can be used for multiple images in general. Effects of pretreatment of the images are discussed. PMID- 17726677 TI - SuperHirn - a novel tool for high resolution LC-MS-based peptide/protein profiling. AB - Label-free quantification of high mass resolution LC-MS data has emerged as a promising technology for proteome analysis. Computational methods are required for the accurate extraction of peptide signals from LC-MS data and the tracking of these features across the measurements of different samples. We present here an open source software tool, SuperHirn, that comprises a set of modules to process LC-MS data acquired on a high resolution mass spectrometer. The program includes newly developed functionalities to analyze LC-MS data such as feature extraction and quantification, LC-MS similarity analysis, LC-MS alignment of multiple datasets, and intensity normalization. These program routines extract profiles of measured features and comprise tools for clustering and classification analysis of the profiles. SuperHirn was applied in an MS1-based profiling approach to a benchmark LC-MS dataset of complex protein mixtures with defined concentration changes. We show that the program automatically detects profiling trends in an unsupervised manner and is able to associate proteins to their correct theoretical dilution profile. PMID- 17726678 TI - Direct chemiluminescent imaging detection of human serum proteins in two dimensional polyacrylamide gel electrophoresis. AB - A novel chemiluminescence (CL)-based imaging method capable of directly detecting proteins in polyacrylamide gels after electrophoresis is proposed. Human serum proteins are presently detected by a direct CL imaging method after native 2-D PAGE. As a consequence, some proteins, including haptoglobin (Hp), Hp precursor, hemopexin (Hpx) precursor, Ig alpha-1 chain C region, and Complement C3 precursor can be detected and identified by MS and MS/MS techniques. These proteins are all acute phase proteins, which have been defined as biomarkers for certain diseases. Moreover, serum proteins from healthy people and cirrhotic patients were analyzed. A decrease in Hp spots for cirrhotic patients could be confirmed. The CL imaging conditions were optimized, including the concentrations of H(2)O(2) and luminol. The process of CL detection of proteins is simple, and there is no need for specialized equipment. In comparison with the traditional CBB-R250 staining method, the detection sensitivity was improved and the detection period decreased about 70 times. Hence, this technique possesses potentials as a rapid, convenient, and inexpensive analytical technique for protein detection and for the diagnosis of diseases. PMID- 17726679 TI - Quantitative proteomics using uniform (15)N-labeling, MASCOT, and the trans proteomic pipeline. AB - Stable isotope labeling combined with MS is a powerful method for measuring relative protein abundances, for instance, by differential metabolic labeling of some or all amino acids with (14)N and (15)N in cell culture or hydroponic media. These and most other types of quantitative proteomics experiments using high throughput technologies, such as LC-MS/MS, generate large amounts of raw MS data. This data needs to be processed efficiently and automatically, from the mass spectrometer to statistically evaluated protein identifications and abundance ratios. This paper describes in detail an approach to the automated analysis of uniformly (14)N/(15)N-labeled proteins using MASCOT peptide identification in conjunction with the trans-proteomic pipeline (TPP) and a few scripts to integrate the analysis workflow. Two large proteomic datasets from uniformly labeled Arabidopsis thaliana were used to illustrate the analysis pipeline. The pipeline can be fully automated and uses only common or freely available software. PMID- 17726680 TI - Dynamics of protein phosphorylation on Ser/Thr/Tyr in Bacillus subtilis. AB - The Ser/Thr/Tyr phosphoproteome of Bacillus subtilis was analyzed by a 2-D gel based approach combining Pro-Q Diamond staining and [(33)P]-labeling. In exponentially growing B. subtilis cells 27 proteins could be identified after staining with Pro-Q Diamond and/or [(33)P]-labeling and one additional protein was labeled solely by [(33)P] resulting in a total of 28 potentially phosphorylated proteins. These proteins are mainly involved in enzymatic reactions of basic carbon metabolism and the regulation of the alternative sigma factor sigma(B). We also found significant changes of the phosphoproteome including increased phosphorylation and dephosphorylation rates of some proteins as well as the detection of four newly phosphorylated proteins in response to stress or starvation. For nine proteins, phosphorylation sites at serine or threonine residues were determined by MS. These include the known phosphorylation sites of Crh, PtsH, and RsbV. Additionally, we were able to identify novel phosphorylation sites of AroA, Pyk, and YbbT. Interestingly, the phosphorylation of RsbRA, B, C, and D, four proteins of a multicomponent protein complex involved in environmental stress signaling, was found during exponential growth. For RsbRA, B, and D, phosphorylation of one of the conserved threonine residues in their C-termini were verified by MS (T171, T186, T181, respectively). PMID- 17726681 TI - Circadian proteomics of the mouse retina. AB - The circadian clock in the retina regulates a variety of physiological phenomena such as disc shedding and melatonin release. Although these events are critical for retinal functions, it is almost unknown how the circadian clock controls the physiological rhythmicity. To gain insight into the processes, we performed a proteomic analysis using 2-DE to find proteins whose levels show circadian changes. Among 415 retinal protein spots, 11 protein spots showed circadian rhythmicity in their intensities. We performed MALDI-TOF MS and NanoLC-MS/MS analyses and identified proteins contained in the 11 spots. The proteins were related to vesicular transport, calcium-binding, protein degradation, metabolism, RNA-binding, and protein foldings, suggesting the clock-regulation of neurotransmitter release, transportation of the membrane proteins, calcium binding capability, and so on. We also found a rhythmic phosphorylation of N ethylmaleimide-sensitive fusion protein and identified one of the amino acid residues modified by phosphorylation. These findings provide a new perspective on the relationship between the physiological functions of the retina and the circadian clock system. PMID- 17726682 TI - Severe pulmonary hypertension in an adolescent with sickle cell disease. PMID- 17726684 TI - Smoking increases the risk of venous thrombosis and acts synergistically with oral contraceptive use. AB - The results of studies investigating the relationship of smoking with venous thrombosis are inconsistent. Therefore, in the MEGA study, a large population based case-control study, we evaluated smoking as a risk factor for venous thrombosis and the joint effect with oral contraceptive use and the factor V Leiden mutation. Consecutive patients with a first venous thrombosis were included from six anticoagulation clinics. Partners of patients were asked to participate and additional controls were recruited using a random digit dialing method. Participants completed a standardized questionnaire. Individuals with known malignancies were excluded from the analyses, leaving a total of 3,989 patients and 4,900 controls. Current and former smoking resulted in a moderately increased risk of venous thrombosis (odds ratio (OR)(current) 1.43, 95% confidence interval (CI95) 1.28-1.60, OR(former) 1.23, CI95 1.09-1.38) compared with nonsmoking. Adjustment for fibrinogen levels did not substantially change these risk estimates. A high number of pack-years resulted in the highest risk among young current smokers (OR(>or=20 pack-years) 4.30, CI95 2.59-7.14) compared with young nonsmokers. Women who were current smokers and used oral contraceptives had an 8.8-fold higher risk (OR 8.79, CI95 5.73-13.49) than nonsmoking women who did not use oral contraceptives. Relative to nonsmoking noncarriers, the joint effect of factor V Leiden and current smoking led to a 5.0 fold increased risk; for the prothrombin 20210A mutation this was a 6.0-fold increased risk. In conclusion, smoking appears to be a risk factor for venous thrombosis with the greatest relative effect among young women using oral contraceptives. PMID- 17726686 TI - Neuropathy as a presenting feature in fragile X-associated tremor/ataxia syndrome. AB - Peripheral neuropathy is common among patients with fragile X-associated tremor ataxia syndrome (FXTAS). Four patients with FXTAS are described with neuropathy as the presenting feature, two having received a prior diagnosis of Charcot-Marie Tooth (CMT) disease. A fifth is described with neuropathy as the only clinical feature. A functional connection between FXTAS and neuropathy has been suggested by the presence of lamin A/C in the intranuclear, neuronal and astrocytic inclusions of FXTAS, since mutations in lamin A/C are known to give rise to an axonal form of CMT. PMID- 17726687 TI - Cleft lip with or without cleft palate: frequency in different ethnic populations from the UCSF craniofacial clinic. PMID- 17726688 TI - Social, emotional, and behavioral functioning of children with NF1. AB - Children with neurofibromatosis type 1 (NF1) can have varying degrees of cognitive impairment, and are at risk for social, emotional, and behavioral dysfunction. We undertook an evaluation of social, emotional, and behavioral functioning of youth with NF1 and peers from multiple perspectives. We hypothesized that children with NF1 would have more psychosocial difficulties, which would be positively associated with neurological involvement. We compared 58 children with NF1, ages 7-15, with comparison classroom peers, classmates who were same race/gender and closest date of birth. Peer relationships, emotional well-being, and behavior were evaluated from multiple perspectives in multiple settings. Results showed that teachers perceived children with NF1 as more prosocial (i.e., polite, helpful to others). Teachers and peers viewed children with NF1 as displaying less leadership behavior and as more socially sensitive isolated (i.e., often left out, trouble making friends). Children with NF1 had fewer friendships and were less well liked by peers. Mothers and fathers reported more problems with social functioning among children with NF1. Few group differences in emotional well-being and behavior were identified according to child and father report. However, mothers perceived children with NF1 to have more emotional problems relative to comparison peers, predominantly among older children. Neurological involvement was significantly related to psychosocial problems. We conclude that children with NF1 are frequently socially isolated and rejected by peers; and that greater neurological involvement is associated with more emotional problems. Central nervous system involvement appears to play a key role in identifying children at risk for problems with friendships, social acceptance, and emotional functioning (i.e., depression). PMID- 17726683 TI - Characteristics of participants with self-reported hemochromatosis or iron overload at HEIRS study initial screening. AB - There are few descriptions of young adults with self-reported hemochromatosis or iron overload (H/IO). We analyzed initial screening data in 7,343 HEmochromatosis and IRon Overload Screening (HEIRS) Study participants ages 25-29 years, including race/ethnicity and health information; transferrin saturation (TS) and ferritin (SF) measurements; and HFE C282Y and H63D genotypes. We used denaturing high-pressure liquid chromatography and sequencing to detect mutations in HJV, TFR2, HAMP, SLC40A1, and FTL. Fifty-one participants reported previous H/IO; 23 (45%) reported medical conditions associated with H/IO. Prevalences of reports of arthritis, diabetes, liver disease or liver cancer, heart failure, fertility problems or impotence, and blood relatives with H/IO were significantly greater in participants with previous H/IO reports than in those without. Only 7.8% of the 51 participants with previous H/IO reports had elevated TS; 13.7% had elevated SF. Only one participant had C282Y homozygosity. Three participants aged 25-29 years were heterozygous for potentially deleterious mutations in HFE2, TFR2, and HAMP promoter, respectively. Prevalences of self-reported conditions, screening iron phenotypes, and C282Y homozygosity were similar in 1,165 participants aged 30 years or greater who reported previous H/IO. We conclude that persons who report previous H/IO diagnoses in screening programs are unlikely to have H/IO phenotypes or genotypes. Previous H/IO reports in some participants could be explained by treatment that induced iron depletion before initial screening, misdiagnosis, or participant misunderstanding of their physician or the initial screening questionnaire. PMID- 17726689 TI - Risk factors for isolated biliary atresia, National Birth Defects Prevention Study, 1997-2002. AB - Biliary atresia is a rare birth defect that affects 1 in 12,000 to 1 in 19,500 live births. We used data from the National Birth Defects Prevention Study, a multistate case-control study, to identify potential risk factors for isolated biliary atresia (no additional unrelated major birth defects diagnosed). Infants were identified from eight states from 1997 to 2002, with clinical information abstracted from medical records. Potential risk factors assessed include: demographic factors, seasonality, preterm birth, maternal smoking, maternal alcohol use, maternal illicit drug use, maternal health, maternal medication use, maternal vitamin use, and maternal nutrition. Infants of non-Hispanic black mothers were more likely to have biliary atresia than infants of non-Hispanic white mothers (adjusted odds ratio (aOR) = 2.29, 95% confidence interval (CI) 1.07-4.93) and infants conceived during the spring season were more likely to have biliary atresia than infants conceived in winter (aOR = 2.33, 95%CI 1.05 5.16). Low intakes of vitamin E, copper, phosphorus, and beta tocopherol were associated with the occurrence of isolated biliary atresia (borderline significance). Low iron intake had a borderline inverse association with biliary atresia. While this analysis provides support for previous reports of a possible association between seasonal variation and the occurrence of biliary atresia, more data are needed to evaluate whether the seasonal variation is related to infectious agents. The role of nutrients in the development of biliary atresia remains unclear. Further studies of genetic, infectious, and nutrient exposures and the association of biliary atresia are warranted. PMID- 17726690 TI - NAT2 variation and idiopathic talipes equinovarus (clubfoot). AB - Idiopathic talipes equinovarus (ITEV), or isolated clubfoot, is a common developmental anomaly that is characterized by a rigid foot, adducted forefoot, cavus midfoot, equinovarus of the hindfoot, and hypoplastic calf musculature. The etiology of this common birth defect is largely unknown, but genetic factors have been implicated in population and family studies and maternal smoking during pregnancy has been identified as an environmental risk factor. The biotransformation of exogenous substances, such as tobacco smoke, is modulated by numerous genes including N-acetylation genes, NAT1 and NAT2. Functional variants of these genes exist and can be distinguished by genotyping. We hypothesized that variation in NAT1 and NAT2 genes might be associated with ITEV. To test this hypothesis, NAT1 and NAT2 were genotyped in a sample of 56 multiplex ITEV families, 57 trios with a positive family history and 160 simplex trios with ITEV. The results detected a slight decrease in the expected number of homozygotes for the NAT2 normal allele in the Hispanic simplex trios. In addition, in a pilot case-control study of ITEV, there were significantly more slow NAT2 acetylators among the cases. This suggests that slow acetylation may be a risk factor for ITEV. This study is the first to find evidence suggesting a role for a biotransformation candidate gene in the etiology of ITEV and provides a scientific foundation to further explore the contributions of other tobacco metabolism genes in the etiology of clubfoot. PMID- 17726691 TI - Ophthalmo-acromelic syndrome: report of a case with vertebral anomalies. PMID- 17726692 TI - Nanoscale surface electrical properties of zinc oxide films investigated by conducting atomic force microscopy. AB - In this study, conducting atomic force microscopy was employed to investigate the nanoscale surface electrical properties of zinc oxide (ZnO) films prepared by pulsed laser deposition (PLD) at different substrate temperatures for use as anode materials in polymer light-emitting diodes. The results show that the surface conductivity distribution of ZnO is related to its surface structure. At substrate temperatures of 150-200 degrees C, the conducting regions may cover over 90% of the ZnO thin-film surface, thus providing the best local conductivity. Moreover, heating at substrate temperatures of above 250 degrees C can effectively make the conductivity on the ZnO surface uniform. In particular, at substrate temperatures of around 300 degrees C, the conducting regions where currents are between 1 and 2 muA may cover as much as 83% of the surface, and furthermore, the transmission ratio in the visible range is higher than 80%. This is a rather ideal production temperature for the PLD for ZnO films. PMID- 17726693 TI - Different membrane modifications revealed by atomic force/lateral force microscopy after doping of human pancreatic cells with Cd, Zn, or Pb. AB - The interaction of the cytotoxic metals cadmium, zinc, and lead with pancreatic cells was studied by atomic force/lateral Force microscopy (AFM/LFM), an approach that provides both topographic (with nanometer scale lateral resolution) and chemical information on the membrane. Different morphological modifications of the overall cell shape and roughness took place as consequence of 100 muM metal dependent treatment. Furthermore, after exposure to Cd(Cl(2)) and Zn(Cl(2)), but not Pb(Cl(2)), the LFM images revealed several areas of the cell's surface showing lateral friction contrasts that have been interpreted as marker of different alterations of the cell physiology induced by the metal loading. Thus, the coupling of LFM detection to topographic AFM characterization allows to distinguish, through a nondestructive and surface characterising approach, between different metal-induced cytotoxic effects on cells. In this framework, the role of the LFM as an important tool to discriminate between different alteration of a biological system has to be highlighted. PMID- 17726694 TI - Keipert syndrome (Nasodigitoacoustic syndrome) is X-linked and maps to Xq22.2 Xq28. AB - Keipert syndrome is a rare condition comprising sensorineural deafness associated with facial and digital abnormalities. To date, Keipert syndrome has been reported in six male patients including two sib pairs; however the genetic basis of Keipert syndrome is yet to be elucidated. We report on the diagnosis of Keipert syndrome in the nephew of the brothers in the first report of Keipert syndrome, with a pedigree consistent with X-linked recessive inheritance. Linkage analysis using microsatellite markers along the X-chromosome suggests that the gene for Keipert syndrome is located in the region Xq22.2-Xq28. We postulate the Keipert syndrome is caused by a novel gene at Xq22.2-Xq28. PMID- 17726695 TI - Chemical pollution, respiratory allergy and asthma: a perspective. AB - The European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) convened a workshop in June 2005 to address the speculation that exposure to specific chemicals, and/or chemical pollutants in general, may play an important role in the increased prevalence of allergy and asthma in 'westernized' societies. This paper summarises one perspective arrived at during this workshop. It was acknowledged that certain chemicals and certain types of pollution might trigger or exacerbate asthmatic reactions in sensitised subjects. However, overall levels of pollution appear not to have had a major impact upon the prevalence of atopic allergy. Epidemiological studies suggest that pollution may in some circumstances protect from acquisition of sensitisation. Increasing exposure to household chemicals may enhance pre-existing allergies, but evidence for their causation of allergy is lacking. Other risk factors considered included societal dietary changes and exposure to endotoxins. Future research needs were identified which included epidemiological studies employing exposure and biomonitoring data, studies on domestic exposure to chemicals and their association with the incidence of allergy and asthma, and prospective birth cohort studies employing well-defined aspects of lifestyle, diet, chemical and endotoxin exposure as factors that may drive susceptibility to allergy and asthma. PMID- 17726697 TI - A structured simple form for ordering genetic tests is needed to ensure coupling of clinical detail (phenotype) with DNA variants (genotype) to ensure utility in publication and databases. AB - Researchers and clinicians ideally need instant access to all the variation in their gene/locus of interest to efficiently conduct their research and genetic healthcare to the highest standards. Currently much key data resides in the laboratory books or patient records around the world, as there are many impediments to submitting this data. It would be ideal therefore if a semiautomated pathway was available, with a minimum of effort, to make the deidentified data publicly available for others to use. The Human Variome Project (HVP) meeting listed 96 recommendations to work toward this situation. This article is planned to initiate a strategy to enhance the collection of phenotype and genotype data from the clinician/diagnostic laboratory nexus. Thus, the aim is to develop universally applicable forms that people can use when investigating patients for each inherited disease, to assist in satisfying many of the recommendations of the HVP Meeting [Cotton et al., 2007]. We call for comment and collaboration in this article. PMID- 17726696 TI - The novel human SHOX allelic variant database. AB - Short stature due to SHOX deficiency represents the most commonly known form of growth failure, with a frequency greater than 1:1,000 in the Caucasian population. As many different mutations can cause SHOX haploinsufficiency, a comprehensive collection of gene variants represents an essential tool to distinguish between functional variants and polymorphisms. We have created a novel and widely extended SHOX database using the "LOVD in a box-solution." This database contains not only a larger amount of mutation data (140 novel mutations were added), but also reports on phenotypic consequences, mode of inheritance, and ethnic origin, as well as on functional consequences of mutations investigated. In addition, the database now includes non-disease-related polymorphisms to enable researchers to evaluate their diagnostic findings. The database (Available at: http://hyg-serv-01.hyg.uni heidelberg.de/lovd/index.php?select_db=SHOX; Last accessed: 12 April 2007) contains all presently known 199 intragenic mutations (SNPs as well as small deletions and insertions), 126 of which are unique. The remote user is able to search the data and to submit new mutations into the database. Furthermore, it includes general information about the SHOX gene via links to other resources such as MIM, GDB, HGMD, and HAPMAP, as well as websites of Short Stature Associations. PMID- 17726699 TI - Genetic changes in the evolution of multidrug resistance for cultured human ovarian cancer cells. AB - The multidrug resistant (MDR) phenotype is often attributed to the activity of ATP-binding cassette (ABC) transporters such as P-glycoprotein (ABCB1). Previous work has suggested that modulation of MDR may not necessarily be a single gene trait. To identify factors that contribute to the emergence of MDR, we undertook integrative genomics analysis of the ovarian carcinoma cell line SKOV3 and a series of MDR derivatives of this line (SKVCRs). As resistance increased, comparative analysis of gene expression showed conspicuous activation of a network of genes in addition to ABCB1. Functional annotation and pathway analysis revealed that many of these genes were associated with the extracellular matrix and had previously been implicated in tumor invasion and cell proliferation. Further investigation by whole genome tiling-path array CGH suggested that changes in gene dosage were key to the activation of several of these overexpressed genes. Remarkably, alignment of whole genome profiles for SKVCR lines revealed the emergence and decline of specific segmental DNA alterations. The most prominent alteration was a novel amplicon residing at 16p13 that encompassed the ABC transporter genes ABCC1 and ABCC6. Loss of this amplicon in highly resistant SKVCR lines coincided with the emergence of a different amplicon at 7q21.12, which harbors ABCB1. Integrative analysis suggests that multiple genes are activated during escalation of drug resistance, including a succession of ABC transporter genes and genes that may act synergistically with ABCB1. These results suggest that evolution of the MDR phenotype is a dynamic, multi-genic process in the genomes of cancer cells. PMID- 17726700 TI - The putative tumor suppressor AIM2 is frequently affected by different genetic alterations in microsatellite unstable colon cancers. AB - Mismatch repair (MMR) deficiency is a major mechanism of colorectal tumorigenesis that is observed in 10-15% of sporadic colorectal cancers and those associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. MMR deficiency leads to the accumulation of mutations mainly at short repetitive sequences termed microsatellites, constituting the high level microsatellite instability (MSI-H) phenotype. In recent years, several genes have been described that harbor microsatellites in their coding region (coding microsatellites, cMS) and are frequently affected by mutations in MMR-deficient cancers. However, evidence for a functional role of most of the known cMS-containing genes is missing, and further analyses are needed for a better understanding of MSI tumorigenesis. Here, we examined in detail alterations of the absent in melanoma 2 (AIM2) gene that shows a high frequency of cMS frameshift mutations in MSI-H colorectal, gastric, and endometrial tumors. AIM2 belongs to the HIN-200 family of interferon (IFN)-inducible proteins, its role in colon carcinogenesis, however, is unknown. Sequencing of the entire coding region of AIM2 revealed a high frequency of frameshift and missense mutations in primary MSI-H colon cancers (9/20) and cell lines (9/15). Biallelic AIM2 alterations were detected in 8 MSI-H colon tumors and cell lines. In addition, AIM2 promoter hypermethylation conferred insensitivity to IFN-gamma-induced AIM2 expression of three MSI-H colon cancer cell lines. These results demonstrate that inactivation of AIM2 by genetic and epigenetic mechanisms is frequent in MMR-deficient colorectal cancers, thus suggesting that AIM2 is a mutational target relevant for the progression of MSI-H colorectal cancers. PMID- 17726701 TI - Dornase alfa is well tolerated: data from the epidemiologic registry of cystic fibrosis. AB - After closure of the Epidemiologic Registry of Cystic Fibrosis (ERCF), a comprehensive safety analysis of dornase alfa was performed. A planned subanalysis focused on children under 5 years old. Reported serious adverse events (SAEs) were assigned a preferred term and ascribed to a specific organ system. Possible serious adverse reactions to dornase alfa (SADRs) were identified by reporting clinics. Twenty-eight of 15,865 SAEs (0.18%), occurring in 26 of 6,829 patients ever treated with dornase alfa (0.38%), and no deaths were reported as possible SADRs: most were typical complications of cystic fibrosis (CF). There was no evidence of any unrecognized risk of treatment. During 24,586 patient-years of follow-up (FU) of ever-treated patients, SAEs (mostly typical respiratory complications of CF) were more frequent on-treatment (0.4999/patient-year; 95% CI 0.4921-0.5076) than off-treatment (0.3889; 0.3787 0.3992). This was likely caused by within-patient prescription bias. During 655 patient-years of FU in 328 ever-treated patients under 5 years old, SAEs (mostly pulmonary exacerbations of CF) were slightly less frequent during treatment: 0.2911 (0.2367-0.3455) versus 0.3563 (0.3086-0.4040; ns). Results confirm the safety of dornase alfa in CF patients of all ages. Children under 5 years old tolerate dornase alfa at least as well as older patients. PMID- 17726703 TI - Dysplasia: a review. AB - Bronchopulmonary dysplasia (BPD) is a common perinatal complication of very low birth weight preterm infants with a significant risk of long-term disability and morbidity. While clinical conditions such as prematurity and mechanical ventilation are its major risk factors, studies suggest that there is an individual susceptibility to BPD. This comprehensive review summarizes data collected about the implication of genetic polymorphisms in BPD and in its risk factors. Some studies have directly related the risk of BPD to genotype. Indeed, carrier states of genetic variants of cytokines (IFNgamma T+874A), adhesion molecules (L-selectin-Pro213Ser), elements of renin-angiotensin system (ACE-I/D), antioxidant enzymes (GST-P1 Val105Ile), and surfactant proteins (SPA1, SPB intron 4) has been identified as risk factors to BPD. Other studies investigated the role of genotype in BPD risk factors. Premature birth has been linked to carrier states of genetic variants with an impact on immune status (such as IL-6 G( 174)C, MBL2 54G/A, VEGF G+405C, HSP72 A+1267G genes) and matrix metalloproteases. Fetal inflammatory response syndrome, a major determinant of BPD is also affected by genotype (including LTalpha A+250G). Disturbed intrauterine lung development and vascularization may also contribute to BPD; these processes may be impaired in the presence of some rare genetic mutations. Furthermore, there is also a genetic component in the susceptibility to other perinatal adaptational disturbances such as respiratory distress syndrome that are associated with an increased need for mechanical ventilation, and, hence, with lung damage. The genetic variants presented in this article may help to identify infants at risk for BPD. PMID- 17726702 TI - The influence of maternal respiratory infections during pregnancy on infant lung function. AB - INTRODUCTION: We studied whether maternal respiratory infections during pregnancy adversely influence lung growth and development of the offspring, resulting in poor early life lung function. METHODS: Infants were participants of the Wheezing Illnesses Study Leidsche Rijn (WHISTLER). Lung function measurements (single occlusion technique) were performed during natural sleep. Questionnaire data were used to obtain information on maternal respiratory infections during pregnancy. Multivariate analysis was conducted to assess the relationship between maternal respiratory infections during pregnancy and resistance and compliance of the respiratory system, adjusting for potential confounding variables. RESULTS: Lower values of compliance (Crs) were found in infants of mothers with respiratory infections during pregnancy; Crs fell by 5.5% (P = 0.031). The difference in Crs between infants of mothers with and without respiratory infections during pregnancy remained unchanged and statistically significant after adjusting for potential confounding variables. The more respiratory infections the mother experienced during pregnancy, the lower the value of Crs was in her offspring (P for trend = 0.016). Using Crs corrected for body weight the relationship with maternal infections was non-significant, however still showing a trend. CONCLUSIONS: The results of this study may indicate that mothers who experience respiratory infections during pregnancy have newborns with lower compliance of the respiratory system. PMID- 17726704 TI - Reference equations for pulmonary function tests in preschool children: a review. AB - Recent developments in pulmonary function tests (PFTs) in preschool children (2-5 years of age) have meant that objective assessments of respiratory function are now possible for this age group. However, the application and interpretation of these tests may be limited by the relative paucity of appropriate reference equations. This review summarizes available preschool reference equations, identifies the current gaps and limitations in the methodologies and statistics used and proposes future directions for improving reference data. A PubMed search which included the MeSH terms (preschool [2-5years]), (respiratory function test), and (reference value) yielded 214 publications which were screened to identify 34 publications presenting 36 reference equations for seven techniques. There were considerable differences with respect to population characteristics, recruitment strategies, equipment and methodologies and reported parameters both within and between each measurement technique. Despite an increasing number of reference equations for PFT for preschool children, the extent to which these can be generalized to other populations may be limited in some cases by inclusion of relatively few children less than 5 years of age, a lack of details regarding the sample populations and measurement techniques and/or inappropriate statistical analysis. A fresh approach based on large sample sizes, clearly documented population characteristics, equipment and protocols, and more rigorous modern statistical methods both for developing reference equations and interpreting results could enhance clinical application of these tests. This in turn would maximize the tremendous opportunities to detect early lung disease offered by the recent surge in developing suitable tests for preschool children. PMID- 17726706 TI - Comparison of atopic and nonatopic children with chronic cough: bronchoalveolar lavage cell profile. AB - Chronic cough is a common complaint in children and its relationship with asthma is controversial. The aim of the present study was to determine the pattern of airway inflammation in atopic and nonatopic children with chronic cough, and to investigate whether atopy is a predictive factor for eosinophilic inflammation in cough. Bronchoalveolar lavage (BAL; three aliquots of 1 ml/kg saline) was performed in the right middle lobe of 24 (11 atopic and 13 nonatopic) children with persistent cough (8 females, 16 males), mean age 4.7 years (range: 1-11). Atopy was defined as an elevated total serum IgE or a positive RAST test. Both atopic and nonatopic children with persistent cough had an increase in total cells/ml in BAL (atopic: median 39 x 10(4), range: 20-123; nonatopic: median 22 x 10(4), range: 17-132) compared to nonatopic controls (median 11 x 10(4), range 9 30). The increases were mainly in neutrophils (atopic: median 17%, range 2.5 88.5%; nonatopic: median 6%, range 1.0-55.0%) compared to controls (median 1.55%, range 0.5-7.0%; atopics vs. controls, P < 0.005). There were no significant increases in eosinophils, lymphocytes, epithelial cells, or mast cells. Eosinophils were elevated in only 5/11 atopic and none of the nonatopic children. The increased percentage of neutrophils in the BAL fluid of atopic and nonatopic children with persistent cough could be due to an underlying inflammatory process driving the cough, or even conceivably, due to the effect of coughing itself. In this highly selected series, the absence of eosinophilic inflammation in the majority suggests that most would be predicted not to respond to inhaled corticosteroid therapy. This study underscores the need to be cautious about treating coughing children with inhaled corticosteroids, even in the context of a tertiary referral practice. PMID- 17726707 TI - The increased cost of complications in children with status asthmaticus. AB - Status asthmaticus is one of the most common causes of admission to a pediatric intensive care unit (PICU). There is little published data, however, examining the complications associated with the treatment of status asthmaticus in children in the PICU. Our hypothesis was that children experiencing a complication would have an increased duration of hospitalization for status asthmaticus. We performed a retrospective review of the complication profile and hospital course of all children admitted to a PICU with status asthmaticus over a 9 years period. Twenty-two (8%) of the 293 children admitted to the ICU with status asthmaticus experienced one or more complications during their treatment. The most common complications were aspiration pneumonia, ventilator-associated pneumonia, pneumomediastinum, pneumothorax, and rhabdomyolysis. Intubated children were significantly more likely than non-intubated children to experience a complication (RR 15.3; 95% CI 6.7-35). Fifteen (42%) of the 36 intubated children experienced a complication. Intubated children experiencing a complication had significantly longer duration of mechanical ventilation (163 +/- 169 hr vs. 66 +/ 65 hr, P = 0.03), ICU length of stay (237 +/- 180 hr vs. 124 +/- 86 hr, P = 0.02) and hospital charges (US dollars 117,184 +/- 111,191 vs. US dollars 38,788 +/- 27,784; P = 0.001) than intubated children not experiencing a complication. In this review, complications were associated with increased morbidity and duration of hospitalization in children with status asthmaticus, particularly in those intubated as part of their therapy. This suggests that intubation and mechanical ventilation itself may increase the risk of developing a complication in this population. PMID- 17726708 TI - Volume targeted ventilation (volume guarantee) in the weaning phase of premature newborn infants. AB - OBJECTIVE: Several options are currently available in neonatal mechanical ventilation: complete breathing synchronization (patient triggered ventilation, synchronized intermittent positive pressure ventilation--SIPPV); positive pressure flow-cycled ventilation (pressure support ventilation, PSV); and volume targeted positive pressure ventilation (volume guarantee, VG). The software algorithm for the guarantee volume attempts to deliver a tidal volume (Vt) as close as possible to what has been selected by the clinician as the target volume. Main objectives of the present study were to compare patient-ventilator interactions and Vt variability in premature infants recovering from respiratory distress syndrome (RDS) who were weaned by various ventilator modes (SIMV/PSV + VG/SIPPV + VG and SIMV + VG). METHODS: This was a short-term crossover trial in which each infant served as his/her own control. Ten premature infants born before the 32nd week of gestation in the recovery phase of RDS were enrolled in the study. All recruited infants started ventilation with SIPPV and in the weaning phase were switched to synchronized intermittent mandatory ventilation (SIMV). Baseline data were collected during an initial 20-min period of monitoring with the infant receiving SIMV alone, then they were switched to SIPPV + VG for a 20-min period and then switched back to SIMV for 15 min. Next, they were switched to PSV + VG for the study period and switched back to SIMV for a further 15 min. Finally, they were switched to SIMV + VG and, at the end of monitoring, they were again switched back to SIMV alone. RESULTS: Each mode combined with VG discharged comparable Vts, which were very close to the target volume. Among the VG-combined modes, mean variability of Vt from preset Vt was significantly different. Variability from the target value was significantly lower in SIPPV and PSV modes than in SIMV (P < 0.0001 and P < 0.04 respectively). SIPPV + VG showed greater stability of Vt, fewer large breaths, lower respiratory rate, and allowed for lower peak inspiratory pressure than what was delivered by the ventilator during other modes. No significant changes in blood gases were observed after each of the study periods. CONCLUSIONS: With regards to the weaning phase, among combined modes, both of the ones in which every breath is supported (SIPPV/PSV) are likely to be the most effective in the delivery of stable Vt using a low working pressure, thus, at least in the short term, likely more gentle for the neonatal lung. In summary, we can suggest that the VG option, when combined with traditional, patient triggered ventilation, adheres very closely to the proposed theoretical algorithm, achieving highly effective ventilation. PMID- 17726709 TI - Optimized temperature and deadspace correction improve analysis of multiple breath washout measurements by ultrasonic flowmeter in infants. AB - BACKGROUND: Assessment of lung volume (FRC) and ventilation inhomogeneities with ultrasonic flowmeter and multiple breath washout (MBW) has been used to provide important information about lung disease in infants. Sub-optimal adjustment of the mainstream molar mass (MM) signal for temperature and external deadspace may lead to analysis errors in infants with critically small tidal volume changes during breathing. METHODS: We measured expiratory temperature in human infants at 5 weeks of age and examined the influence of temperature and deadspace changes on FRC results with computer simulation modeling. A new analysis method with optimized temperature and deadspace settings was then derived, tested for robustness to analysis errors and compared with the previously used analysis methods. RESULTS: Temperature in the facemask was higher and variations of deadspace volumes larger than previously assumed. Both showed considerable impact upon FRC and LCI results with high variability when obtained with the previously used analysis model. Using the measured temperature we optimized model parameters and tested a newly derived analysis method, which was found to be more robust to variations in deadspace. Comparison between both analysis methods showed systematic differences and a wide scatter. CONCLUSION: Corrected deadspace and more realistic temperature assumptions improved the stability of the analysis of MM measurements obtained by ultrasonic flowmeter in infants. This new analysis method using the only currently available commercial ultrasonic flowmeter in infants may help to improve stability of the analysis and further facilitate assessment of lung volume and ventilation inhomogeneities in infants. PMID- 17726711 TI - Correlates of knowledge and beliefs about depression among long-term care staff. AB - CONTEXT: Despite the high prevalence of depression in long-term care (LTC), it often is unrecognized and inadequately treated. Thus, the goals of the present study were to evaluate LTC staff characteristics that are associated with knowledge and beliefs about depression. METHODS: A cross sectional study of 371 LTC staff members completed a knowledge and beliefs about depression questionnaire, a short demographic questionnaire, a burden measure, and a questionnaire about attitudes associated with working with depressed residents. RESULTS: Relative to nurses, social workers, and activity staff, paraprofessional caregivers had a lower score on the depression measure and a higher score on the burden measure. Paraprofessional caregivers were more likely to view depression as a normal phenomenon, held less accurate beliefs about signs and symptoms of depression, and were less familiar with the effectiveness of specific treatments of depression. CONCLUSIONS: Educational interventions about depression should be specifically geared to meet the needs of paraprofessional caregivers who provide the majority of care to LTC residents, yet possess less knowledge about depression and its treatments. PMID- 17726712 TI - Primary health care reform in Uzbekistan. AB - In recent years, primary health care in Uzbekistan has seen dramatic changes in organization, management and financing. The Soviet multi-tiered system of primary care is being replaced by a two-tiered system, consisting in rural areas of rural physician points (SVPs) and outpatient clinics of central rayon hospitals. A state-guaranteed benefits package of primary care services has been introduced and financing is increasingly based on capitation. In addition, a considerable number of physicians and nurses have been trained in general practice. There are, however, a number of challenges that remain. One of them is the considerable regional differences that exist in health financing. Another challenge is that some rural areas have difficulties attracting primary care workers. Overall, the institutional and financial link between primary and secondary care needs to be strengthened, as at present GPs have an incentive to refer patients to higher levels of care, which is financially inaccessible for large parts of the population. PMID- 17726713 TI - Bonferroni parallel gatekeeping - transparent generalizations, adjusted p values, and short direct proofs. AB - In the two-step version (Dmitrienko, Tamhane, Wang and Chen, 2006) of the Bonferroni parallel-gatekeeping multiple-testing procedure (MTP): (a) a family F1 of null hypotheses H is used as a gatekeeper for another family F2 in that no H in F2 can be rejected unless at least one H is rejected in F1; (b) a Bonferroni MTP is used for F1 at local multiple-level alpha in the first step; and (c) Holm's (1979) step-down MTP is used in the second step for F2 at a local multiple level that depends on the rejections made in the first step. It is shown in this article that this two-step procedure can be generalized in that any MTP with multiple-level control and available multiplicity-adjusted p -values can be used instead of Holm's MTP in the second step. A further generalization related to what Dmitrienko, Molenberghs, Chuang-Stein and Offen (2005) called modified Bonferroni parallel gatekeeping is also given where in case all H s in F2 are rejected, additional rejections in F1 can be made in a third step at local multiple-level alpha through any MTP that is more powerful than the initial Bonferroni MTP, e.g. Holm's MTP. The proofs that these two generalized Bonferroni parallel-gatekeeping MTPs have multiple-level alpha are short and direct, without closed-testing arguments. Multiplicity-adjusted p -values can easily be calculated for these MTPs. The extensions to several successive gatekeeper families are straightforward. An illustration is given. PMID- 17726714 TI - Discrete stochastic models for compliance analysis based on an AIDS Clinical Trial Group (ACTG) study. AB - Compliance is the extent to which a patient follows the prescribed regimen. Here we investigate the statistical properties of two popular measures of compliance - percentage of compliant days and percentage of doses taken. We use a stationary Markov chain to model the dependence structure of successive data points for each subject. We illustrate our model using discrete compliance data collected from an AIDS Clinical Trial Group study (ACTG 398). We check the model assumptions and evaluate the small sample as well as large sample properties of our estimators. We show that ignoring the within-subject dependence will usually underestimate the standard errors of the estimates of these compliance measures. Our model allows the application of meta-analytic approaches to assess the variation across subjects in these compliance indices and changes in them due to intervention. PMID- 17726715 TI - Blinded sample size reestimation in non-inferiority trials with binary endpoints. AB - Sample size calculations in the planning of clinical trials depend on good estimates of the model parameters involved. When the estimates of these parameters have a high degree of uncertainty attached to them, it is advantageous to reestimate the sample size after an internal pilot study. For non-inferiority trials with binary outcome we compare the performance of Type I error rate and power between fixed-size designs and designs with sample size reestimation. The latter design shows itself to be effective in correcting sample size and power of the tests when misspecification of nuisance parameters occurs with the former design. PMID- 17726716 TI - Comparison of ROC umbrella volumes with an application to the assessment of lung cancer diagnostic markers. AB - Receiver operating characteristic (ROC) analysis is widely used to assess the ability of diagnostic markers to correctly classify into one of two disease classes. ROC surfaces and umbrella surfaces generalize the utility of ROC analysis when there are three disease classes. Identification of lung cancer diagnostic markers is an active area of research since prognosis for those diagnosed with lung cancer is so poor and there is not an accurate method for early detection of lung cancer. A study conducted for the assessment of DNA methylation markers motivated the comparison of ROC umbrella surfaces which is developed in this article using U-statistics and bootstrap methodology. PMID- 17726717 TI - Testing and estimating the non-disjunction fraction in Meiosis I using reference priors. AB - In this paper we analyze the fraction of non-disjunction in Meiosis I assuming reference (non-informative) priors. We consider Jeffreys's approach to built a non-informative prior (Jeffreys's prior) for the fraction of non-disjunction in Meiosis I. We prove that Jeffreys's prior is a proper distribution. We perform Monte Carlo studies in order to compare Bayes estimates obtained assuming Jeffreys's and uniform priors. We consider full Bayesian significance test (FBST) and Bayes factor (BF) for testing precise hypothesis on the fraction of non disjunction in Meiosis I. The ultimate goal of this paper is to compare these two test procedures through simulation studies using both prior specifications. An application to Down Syndrome data is also presented. PMID- 17726718 TI - Practice style in the nursing home: dimensions for assessment and quality improvement. AB - OBJECTIVE: Based on research staff observations during several studies in nursing homes and the findings of other studies, we propose a nomenclature of components of care for the elderly in nursing homes. The paper seeks thereby to operationalize those aspects of the nursing home practice style that can be improved. METHODS: This operationalization examines two main components (staff and institutional components) of practice style of care in nursing homes. Four domains characterize staff conduct (knowledge, practice style proficiency, flexibility and individualization of care and communication) and three domains define institutional conduct (staff support, resources and flexibility/rigidity of policies). RESULTS: The paper addresses critical aspects of staff conduct, and by extension, key features that require training, monitoring, and systemic change. Examples for each domain of practice style are provided. CONCLUSIONS: After systematically reviewing the observations and findings it was concluded that enhancing practice styles in the nursing home requires knowledge, communication, flexibility, understanding, and genuine concern on the part of nursing home staff and administrators at all levels. We acknowledge and understand, of course, that changing practice styles in nursing homes is a difficult and time-consuming process. PMID- 17726719 TI - Lipid transfer proteins from Brassica campestris and mung bean surpass mung bean chitinase in exploitability. AB - Antifungal peptides with a molecular mass of 9 kDa and an N-terminal sequence demonstrating remarkable similarity to those of nonspecific lipid transfer proteins (nsLTPs) were isolated from seeds of the vegetable Brassica campestris and the mung bean. The purified peptides exerted an inhibitory action on mycelial growth in various fungal species. The antifungal activity of Brassica and mung bean nsLTPs were thermostable, pH-stable, and stable after treatment with pepsin and trypsin. In contrast, the antifungal activity of mung bean chitinase was much less stable to changes in pH and temperature. Brassica LTP inhibited proliferation of hepatoma Hep G2 cells and breast cancer MCF 7 cells with an IC(50) of 5.8 and 1.6 microM, respectively, and the activity of HIV-1 reverse transcriptase with an IC(50) of 4 microM. However, mung bean LTP and chitinase were devoid of antiproliferative and HIV-1 reverse transcriptase inhibitory activities. In contrast to the mung bean LTP, which exhibited antibacterial activity, Brassica LTP was inactive. All three antifungal peptides lacked mitogenic activity toward splenocytes. These results indicate that the two LTPs have more desirable activities than the chitinase and that there is a dissociation between the antifungal and other activities of these antifungal proteins. PMID- 17726721 TI - Zinc-leuprolide complex: preparation, physicochemical characterization and release behaviour from in situ forming implant. AB - Leuprolide acetate (LA) has been accepted as treatment for prostatic cancer and is currently also being evaluated in phase II clinical trials for the treatment of Alzheimer's disease. In this study, the zinc complex of leuprolide was prepared and its structure determined by Fourier-transform infrared (FTIR), differential scanning calorimetry (DSC), UV, X-ray diffraction (XRD), atomic absorption spectroscopy, elemental analysis, and compared with these parameters for leuorolide acetate. Also, the in vitro release profile of leuprolide and its complex form in situ forming implant (ISFI) in comparison to a commercial formulation (Eligard) was investigated. These studies indicate that the zinc complex can be effectively synthesized and influenced on tri-phasic pattern after burst release of LA from the ISFI and shifts this trend to a continuous release profile. Non-linear regression test confirmed this transformation as a zero-order release profile as well. PMID- 17726720 TI - The specificity of neuropsychological impairment in predicting antidepressant non response in the very old depressed. AB - OBJECTIVE: In an earlier report, response inhibition predict antidepressant non response in late-life depression (Sneed et al., 2007). The purpose of this study was to ascertain whether this effect is specific to response inhibition or whether impairment in other cognitive domains also predicts non-response. METHOD: Older depressed patients (n = 84) enrolled in an 8-week trial of citalopram were classified as impaired or non-impaired relative to the sample on mental status, psychomotor speed, reaction time, spatial judgment, and memory, and contrasted with regard to antidepressant response. RESULTS: Patients who were impaired relative to the sample on digit symbol performance did not respond as quickly to citalopram as those who were unimpaired. By the end of the 8-week trial, however, both groups reached the same level of response. Impairment in other domains had no impact on antidepressant response. CONCLUSIONS: Non-response was not attributable to impairment on any of the neuropsychological tests suggesting that antidepressant non-response is specific to impaired response inhibition. PMID- 17726722 TI - Fast Fmoc synthesis of hAmylin1-37 with pseudoproline assisted on-resin disulfide formation. AB - Human amylin (1-37) and the (1-13) fragment were synthesized with and without pseudoproline dipeptides. Thallium (III) trifluoroacetate, a mild oxidant, was used to cyclize the peptides by forming a disulfide bridge from C(2) to C(7). On the basis of our model studies, incorporation of a pseudoproline dipeptide decreases the amount of time necessary for the crude linear amylin (1-13) to cyclize on the resin. Without pseudoproline dipeptides, the 1-37 crude linear amylin was not pure enough to undergo the cyclization reaction. Following the cyclization studies, the synthesis time of the linear human amylin (1-37) was systematically reduced from 58 h to 8.5 h by shortening the reaction times. Cyclization and cleavage times were also reduced to 1.5 h. PMID- 17726724 TI - D-optimal cohort designs for linear mixed-effects models. AB - The D-optimality criterion is used to construct optimal designs for different numbers of independent cohorts, which constitute a number of repeated measurements per subject over time. A cost function for longitudinal data is proposed, and the optimality criterion is optimized taking into account the cost of the study. First, an optimal number of design points for a given number of cohorts and cost was identified. Then, an optimal number of cohorts is identified by comparing the relative efficiencies (REs). A numerical study shows that for models describing the trend of a continuous outcome over time by polynomials, the most efficient number of repeated measurements is equal to the sum of the total number of cohorts and the degree of the polynomial in the model. REs of a purely longitudinal cohort design with only one cohort, and mixed longitudinal and cross sectional cohort designs with more cohorts are compared. The results show that a purely longitudinal cohort design with only one cohort of subjects measured at the optimal time points is the most efficient design. The findings in this paper show that one can obtain a highly efficient design for parameter estimation with only a few repeated measurements. The results of this study will reduce the cost of data collection and ease the logistical burdens in cohort studies. PMID- 17726723 TI - Effects of acute paroxetine treatment on the consumption of cigarette smoking and caffeine in depressed patients. AB - In the present study, we examined the effects of acute treatment with paroxetine on the consumption of cigarette smoking and caffeine in 65 patients who met the DSM-IV criteria for major depressive disorder (M/F: 28/37, age: 48 +/- 15 years). Plasma levels of cotinine or caffeine were analysed using high-performance liquid chromatography (HPLC). The amount of cigarette smoking and plasma levels of cotinine, but not caffeine, decreased 4 weeks after paroxetine treatment. There was no difference between smokers and nonsmokers with respect to their response to paroxetine treatment. In addition, plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in responders to paroxetine treatment was higher than those in nonresponders, and there was a negative correlation between the changes in plasma MHPG levels and the changes in Hamilton rating scale for depression (Ham-D) scores before and 4 weeks after paroxetine administration. These results suggest that paroxetine has the potential to reduce the amount of cigarette smoking in depressed smokers, and we reconfirmed our previous results that depressed patients with higher plasma MHPG levels had better response to paroxetine treatment than those with lower plasma MHPG levels using larger depressed samples. PMID- 17726725 TI - No evidence for an association between G protein beta3 subunit gene C825T polymorphism and tardive dyskinesia in schizophrenia. AB - OBJECTIVE: Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotic. We evaluated candidate functional polymorphism of the G protein beta3 subunit (GNB3) gene for association with drug-induced TD in the Korean schizophrenic patients. METHODS: We investigated whether the C825T polymorphism of the GNB3 gene is associated with the TD in a Korean sample of schizophrenic patients with (n = 83) and without TD (n = 126), matched for antipsychotic drug exposure and other relevant variables. RESULTS: The distribution of genotypes and allele frequencies of GNB3 were not different between schizophrenic patients with TD and without TD (p > 0.05). CONCLUSION: Within the limitations imposed by the size of the clinical sample, these findings suggest that the GNB3 825 C/T single nucleotide polymorphism (SNP) does not contribute significantly to risk for TD. PMID- 17726726 TI - Prenatal diagnosis of diastematomyelia: presentation of eight cases and review of the literature. AB - OBJECTIVES: Diastematomyelia is a rare form of spinal dysraphism. We present eight cases of diastematomyelia diagnosed prenatally in our institution as well as a review of the literature in order to determine the prognosis of isolated cases of this very unusual condition. METHODS: Records of fetuses with diastematomyelia diagnosed in our institution between January 2000 and June 2005 were collected. All liveborn fetuses were examined by a pediatric neurologist. Pre- and postnatal data were analyzed. A search was then conducted using PubMed to review previously reported cases in the literature. RESULTS: Eight cases of diastematomyelia were diagnosed during the study interval. The mean (range) gestational age at diagnosis was 21 (13-25) weeks. The main sonographic findings were widening of the spinal canal in the coronal view and an additional echogenic focus in the posterior part of the spinal column in the axial view. The diagnosis of associated open spina bifida was made in one fetus with elevated levels of amniotic fluid alpha-fetoprotein (AF-AFP) and acetylcholinesterase (AF-AChE) and the pregnancy was terminated. The other seven cases of diastematomyelia had normal levels of AF-AFP and AF-AChE and were considered isolated. One pregnancy miscarried spontaneously 1 week following amniocentesis and the remaining six were delivered at term. Review of the literature revealed 14 reports involving 26 cases of prenatally diagnosed diastematomyelia. Twelve cases had normal biochemistry and/or no additional abnormalities and all had a favorable outcome. CONCLUSIONS: When diastematomyelia is not associated with other spinal anomalies, the prognosis is favorable. Prenatal diagnosis is generally made in the second trimester but sonographic signs may be recognized as early as the first trimester. Intrauterine diagnosis of diastematomyelia should facilitate appropriate management of affected cases. PMID- 17726727 TI - Postnatal development of pups from nursing rats treated with Gingko biloba. AB - The Gingko biloba extract is contraindicated during pregnancy and lactation due to the lack of information about its effects on these reproductive phases. Previous studies have shown that G. biloba extract contains components with estrogenic and antiestrogenic activities, thus nursing dams treated with the extract of this plant could show reduction in milk production, resulting in malnutrition and poor development of pups. This work analyzes the postnatal development of pups, whose mothers were treated with G. biloba extract during the lactation period. Nursing Wistar rats received 3.5 mg/kg/day of G. biloba aqueous extract, corresponding to the highest human dose. Clinical signs of maternal toxicity were evaluated. The growth rate, viability, survival during treatment and lactation indices of the pups were calculated. The physical, motor and sensorial development of the pups was also evaluated. No maternal signs of toxicity were observed. As there were no biological differences between control and G. biloba treated pups, it is possible to assume that, in this experimental design, the administration of G. biloba aqueous extract to nursing rats during the lactation period seems to be devoid of toxic effect to mothers and to the physical, motor and sensory development of the pups. PMID- 17726728 TI - Peanut (Arachis hypogaea) consumption improves glutathione and HDL-cholesterol levels in experimental diabetes. AB - The aim of this investigation was to assess the influence of peanut (Arachis hypogaea) consumption on oxidant-antioxidant status and lipid profile in Streptozotocin (STZ) induced diabetic rats. 32 rats were divided into 4 groups as control, control+peanut, diabetic, diabetic+peanut. Control and diabetic groups were fed on standard rat chow whereas control+peanut and diabetic+peanut were fed on standard rat chow supplemented with 0.63 g % peanut for 12 weeks. Serum glucose levels, lipids, Glutathione (GSH), lipid peroxidation (LPO) and atherogenic index (AI) levels were determined at the end of the experiment. In the diabetic group TG (Triglyceride), TC (Total cholesterol), LDL-C (LDL cholesterol) levels and atherogenic indexes increased significantly whereas HDL-C (HDL-cholesterol) level decreased significantly compared to the control group. The supplementation with peanut in the diabetic group led to significantly higher HDL-C levels and lower AI levels compared to diabetic group. Peanut consumption increased GSH levels significantly both in control and diabetic groups. In conclusion, this study shows that peanut consumption may improve oxidant antioxidant status in healthy and diabetic status without increasing blood lipids. Moreover, increased HDL-C levels and decreased AI levels in diabetic rats indicate that, peanut consumption may have protective effects against cardiovascular complications of diabetes. PMID- 17726729 TI - Determination of genotoxic, antigenotoxic and cytotoxic potential of the extract from lichen Cetraria aculeata (Schreb.) Fr. in vitro. AB - Naturally occurring compounds can have protective effects towards mutagens and carcinogens as shown by numerous studies. In the present study, the genotoxic/antigenotoxic activities of the extract from lichen Cetraria aculeata (Schreb.) Fr., which has been identified as an antibacterial agent in former studies, were investigated against known mutagens such as 4-nitro-o phenylenediamine (4-NPD) and 2-aminofluorene (2-AF) in TA98 and TA100 strains of Salmonella typhimurium in the presence or absence of metabolic activity. Further genotoxicity/antigenotoxicity of the extract against mitomycin C for micronucleus formation was also evaluated in human lymphocytes. The cytotoxic effects of the extract on mammalian cells were investigated in three different cell line types by MTT assay. The results obtained show that the extract of C. aculeata has a significant antigenotoxic activity in bacterial systems, but not in mammalian cells and cytotoxic activity in some mammalian cancer cells. However, it was not mutagenic in all systems. The findings suggest that the lichen extract may have a possible therapeutic potential and therefore this must be further investigated by other multiple in vitro bioassays for the development of therapeutic agents. PMID- 17726730 TI - Comparative study of antioxidant properties of wild growing and cultivated Allium species. AB - Allium species are cultivated for the edible bulb, which is used mainly as flavoring in foods. Besides that, they could prevent tumor promotion and some processes that are associated with free radicals, such as cardiovascular diseases and aging. Therefore, different Allium species, both cultivated (Allium nutans L., A. fistulosum L., A. vineale L., A. pskemense B. Fedtsch, A. schoenoprasum L., A. cepa L. and A. sativum L.) and wild (A. flavum L., A. sphaerocephalum L., A. atroviolaceum Boiss, A. vineale L., A. ursinum L., A. scorodoprasum L., A. roseum L. and A. subhirsutum L.), were investigated in order to evaluate the antioxidant properties of their bulbs. This study reports on the results obtained for the bulb antioxidant enzyme activities (superoxide dismutase, catalase, guaiacol peroxidase, glutathione peroxidase), the quantities of non-enzymatic plant antioxidants (reduced glutathione and total flavonoids), the contents of soluble proteins, vitamin C, carotenoids, chlorophylls a and b, as well as for the quantities of malonyldialdehyde and .OH and O2.- radicals. PMID- 17726731 TI - Pharmacometrics of pterostilbene: preclinical pharmacokinetics and metabolism, anticancer, antiinflammatory, antioxidant and analgesic activity. AB - The present study evaluated the preclinical pharmacokinetics and pharmacodynamics of trans-pterostilbene, a constituent of some plants. Right jugular vein cannulated male Sprague-Dawley rats were dosed i.v. with 20 mg/kg of pterostilbene and samples were analysed by the reverse phase HPLC method. Serum AUC, serum t(1/2), urine t(1/2), Cl(total) and Vd(beta) were 17.5 +/- 6.6 microg/h/mL, 1.73 +/- 0.78 h, 17.3 +/- 5.6 h, 0.960 +/- 0.025 L/h/kg and 2.41 +/- 1.13 L/kg (mean +/- SEM), respectively. A pterostilbene glucuronidated metabolite was detected in both serum and urine. The in vitro metabolism in rat liver microsomes furthermore suggests phase II metabolism of pterostilbene. Pterostilbene demonstrated concentration-dependent anticancer activity in five cancer cell lines (1-100 microg/mL). An in vitro colitis model showed concentration-dependent suppression of PGE(2) production in the media of HT-29 cells. Antiinflammatory activity was examined by inducing inflammation in canine chondrocytes followed by treatment with pterostilbene (1-100 microg/mL). The results showed decreased levels of MMP-3, sGAG and TNF-alpha compared with control levels. Pterostilbene exhibited concentration-dependent antioxidant capacity measured by the ABTS method. Pterostilbene increased the latency period to response in both tail-flick and hot-plate analgesic tests. PMID- 17726732 TI - Activity against drug resistant-tuberculosis strains of plants used in Mexican traditional medicine to treat tuberculosis and other respiratory diseases. AB - Tuberculosis (TB) kills about 3 million people per year worldwide. Furthermore, TB is an infectious disease associated with HIV patients, and there is a rise in multidrug-resistant TB (MDR-TB) cases around the world. There is a need for new anti-TB agents. The study evaluated the antimycobacterial activity of nine plants used in Mexican traditional medicine to treat tuberculosis and other respiratory diseases. Nasturtium officinale showed the best activity (MIC = 100 microg/mL) against the sensitive Mycobacterium tuberculosis. The following plants were active also but at 200 microg/mL: Citrus sinensis, Citrus aurantifolia, Foeniculum vulgare, Larrea tridentata, Musa acuminata and Olea europaea. Contrary to the above data, activity against drug-resistant variants of M. tuberculosis was more evident, e.g. N. officinale was the most potent (MIC < or = 100 microg/mL) against the four mono-resistant variants tested; F. vulgare and O. europaea were active against all the resistant variants (MICs < or = 100 microg/mL). The most susceptible variant was the isoniazid resistant, being inhibited by C. aurantifolia, C. sinensis and O. europaea (MIC = 25 microg/mL). These data point to the importance of biological testing of extracts against drug resistant M. tuberculosis isolates, and the bioguided assay of these extracts for the identification of lead compounds against MDR-TB isolates. PMID- 17726733 TI - Protective effects of an herbal formulation of Radix Astragali, Radix Codonopsis and Cortex Lycii on streptozotocin-induced apoptosis in pancreatic beta-cells: an implication for its treatment of diabetes mellitus. AB - Hyperglycemia is one of the main causes of oxidative stress in type 2 diabetes mellitus. During hyperglycemia, the increased level of various reducing sugars in the blood enhances the production of reactive oxygen species (ROS) and triggers tissue damage, especially in pancreatic beta-cells. Streptozotocin (STZ) is a diabetogen that causes diabetes mellitus via ROS-induced apoptosis in beta-cells. In this study, SR10, an herbal formulation consisting of the aqueous extracts of Radix Astragali, Radix Codonopsis and Cortex Lycii was examined for its antidiabetic effects in vitro. SR10 treatment resulted in significant enhancement of survival rate of rat pancreatic beta-cells which were treated by streptozotocin. SR10 apparently reduced apoptosis of streptozotocin-treated beta cells by decreasing DNA fragmentation, sub-G(1) peak area and percentage of apoptotic cells. Nitric oxide (NO) production in streptozotocin-treated cells was inhibited by SR10 via the suppression of the expression of inducible nitric oxide synthase (iNOS). The implication of SR10 in treating type 2 diabetes mellitus was discussed. PMID- 17726734 TI - Dosing effects of an antiosteoporosis herbal formula--a preclinical investigation using a rat model. AB - Herba Epimedii, Fructus Ligustri Lucidi and Fructus Psoraleae are three frequently used Chinese herbs traditionally used for tonifying the 'kidney system'. They were selected for the present study to formulate an herbal preparation with a weight ratio of 5:4:1 based on their phytochemical, nature, documented treatment efficacy and toxicity. The dosing effects (1 g/day, 0.5 g/day and 0.175 g/day) of the antiosteoporosis function of the water extract of this formula were tested in ovariectomy- and calcium deficiency-induced osteoporotic rats. Eleven weeks of herbal treatment demonstrated a beneficial effect on the preservation of bone mineral density (BMD) at the femur neck in a dose-dependent manner with the preference for higher dosage. No significant increase in uterus weight was observed in the herbal formula treated rats. In addition, microarray data of kidney tissue revealed that this herbal formula was able to down-regulate the expression of phase II drug metabolizing enzymes, similar to the effects of estrogens. PMID- 17726735 TI - Quinic acid esters from Pluchea indica with collagenase, MMP-2 and MMP-9 inhibitory activities. AB - Investigation of collagenase inhibitory natural components afforded two quinic acid esters (1 and 2) and quercetin (3) from the leaves of Pluchea indica (Compositae). Of these, compounds 1 and 2 exhibited collagenase inhibitory activity (IC(50)) at a concentration of less than 10 microm, and 1 showed matrix metalloproteinase (MMP)-2 and -9 inhibitory activity (IC(50)) at 2.5 and 6.4 microm, respectively. PMID- 17726736 TI - Antiinflammatory activity of Lindera erythrocarpa fruits. AB - In this study, in vitro and in vivo antiinflammatory activities of fruits from Lindera erythrocarpa Makino were evaluated. The ethyl acetate soluble fraction derived from the ethanol extract of L. erythrocarpa fruits inhibited significantly nitric oxide (NO) production in lipopolysaccharide (LPS) induced NO in the murine macrophage cell line (RAW264.7) assay, the EC(50) being 16.35 microg/mL. Four compounds, including lucidone (1), cis/trans-methylludicone (2), methyl linderone (3) and linderone (4) were identified from the active fraction based on the bioactivity-guided fractionation procedure. Of these lucidone possessed the strongest NO inhibitory activity with an EC(50) value of 4.22 microg/mL. Furthermore, results from the protein expression assay demonstrated that lucidone suppressed iNOS and COX-2 protein expression in a dose-dependent manner. Lucidone also provided antiinflammatory activity in the croton oil induced ear edema assay. When it was applied topically at a dosage of 0.5 and 1 mg per ear, the percent edema reduction in treated mice was 44% and 25%, respectively. The results obtained in this study indicated that lucidone has a good potential to be developed as an antiinflammation agent. PMID- 17726737 TI - Lipid peroxidation and cyclooxygenase enzyme inhibitory activities of acidic aqueous extracts of some dietary supplements. AB - The botanical supplement market is growing at a fast pace with more and more people resorting to them for maintaining good health. Echinacea, garlic, ginkgo, ginseng, Siberian ginseng, grape seed extract, kava kava, saw palmetto and St John's wort are some of the popular supplements used for a variety of health benefits. These supplements are associated with various product claims, which suggest that they possess cyclooxygenase (COX) enzyme and lipid s inhibitory activities. COX enzymes are found to be at elevated levels in inflamed and cancerous cells. To test some of the product claims, selected supplements were analysed for their ability to inhibit COX-1 and -2 enzymes and lipid peroxidation in vitro. The supplements were extracted with acidified water (pH 2) at 37 degrees C to simulate the gastric environment. The supplements tested demonstrated varying degrees of COX enzyme inhibition (5-85% for COX-1 and 13-28% for COX-2). Interestingly, extracts of garlic (Meijer), ginkgo (Solaray), ginseng (Nature's Way), Siberian ginseng (GNC, Nutrilite, Solaray, Natrol), kava kava (GNC, Sundown, Solaray) and St John's wort (Nutrilite) selectively inhibited COX 2 enzyme. These supplements also inhibited lipid peroxidation in vitro (5-99%). The results indicated that the consumption of these botanical supplements studied possess health benefits. PMID- 17726738 TI - Treatment of PC-3 and DU145 prostate cancer cells by prenylflavonoids from hop (Humulus lupulus L.) induces a caspase-independent form of cell death. AB - Xanthohumol (X), isoxanthohumol (IX), 8-prenylnaringenin (8PN) and 6 prenylnaringenin (6PN), prenylflavonoids from hop (Humulus lupulus L.), were investigated for their cytotoxicity and the mechanism by which they exert cell death when incubated with prostate cancer cell lines PC-3 and DU145. All compounds induced cell death in the absence of caspase-3 activation and typical apoptotic morphological features. The general pan-caspase inhibitor zVAD-fmk could not protect this form of cell death. In addition, the formation of vacuoles was observed in PC-3 cells treated with IX and 6PN, and in DU145 treated with IX, 8PN and 6PN, which could suggest the induction of autophagy and consequent cell death. The results indicate that hop-derived prenylflavanones (IX, 8PN, 6PN), but not prenylchalcones (X) induce a caspase-independent form of cell death, suggested to be autophagy. Therefore, IX, 8PN and 6PN appear to be promising candidates for further investigation in prostate anticancer therapy. PMID- 17726739 TI - Brain metastases of melanoma--mechanisms of attack on their defence system by engineered stem cells in the microenvironment. AB - This report gives a better emphasis on the role of targeted effectors (e.g. a combination of 5-FC with CD-NSPCs as compared to the application of NSPCs alone) and how such delivery of pro-drug activating enzymes and other tumor-killing substances may overcome melanocytic defence system, interact with and promote the host defence and immune response modulations not only in melanoma but, potentially, in other highly-metastatic cancers. PMID- 17726740 TI - Adenoma of nonpigmented epithelium in ciliary body: literature review and case report. AB - Adenomas of the nonpigmented ciliary epithelium (NPCE) are often clinically indistinguishable from amelanotic malignant melanomas of the ciliary body or metastatic carcinomas. This paper reports a case study of a distinctive variant of adenoma of the NPCE, which clinically appears as epiretinal membrane in the macular region. Histopathologic studies have revealed this is an adenoma of the NPCE. Identification of this clinic feature is important because it will miss the diagnosis of the adenoma of the NPCE. In this case study, B-scan ultrasonography as well as computerized tomography (CT) has been used to provide help in diagnosing the ciliary body tumor. Because of their anterior location in the ciliary body, partial lamellar sclerouvectomy is an effective method of treatment. PMID- 17726741 TI - Amniotic membrane transplantation for porous sphere orbital implant exposure. AB - OBJECTIVE: This study is aimed at describing the clinical outcome of amniotic membrane transplantation for exposure of porous sphere implants. METHODS: A retrospective review of consecutive cases of porous sphere orbital implant exposure was carried out. Eight cases were presented between May 2004 and Oct. 2006 (5 males, 3 females; mean age 44.5 years). Six had enucleation and two had evisceration. Exposure occurred in two primary and six secondary. Orbital implant diameter was 22 mm in seven cases and 20 mm in one case. Six patients are with hydroxyapatite and two with high-density porous polyethylene (Medpor) orbital implants. The mean time from implantation to exposure was 1.1 months (range 0.8-2 months). All patients required surgical intervention. RESULTS: The time of follow up ranged from 3.0 to 28.0 months (mean 16.5 months). Amniotic membrane grafting successfully closed the defect without re-exposure in all of these patients. The grafts were left bare with a mean time to conjunctiva of about 1 month (range 0.8 1.5 months). CONCLUSION: Exposed porous sphere implants were treated successfully with amniotic membrane graft in all of patients. The graft is easy to harvest. This technique is useful, dose not lead to prolonged socket inflammation and infection, and it is valuable application extensively. PMID- 17726742 TI - Effect of basic fibroblast growth factor (bFGF) on the treatment of exposure of the orbital implants. AB - OBJECTIVE: To evaluate the efficacy and the indication of basic fibroblast growth factor (bFGF) in the treatment of exposure of orbital implants. DESIGN: Retrospective and observational case series. METHODS: We reviewed 41 patients (41 eyes) suffering exposure of orbital implants from Jan. 2000 to June 2006. The study group patients with mild exposure received combined treatment with bFGF and antibiotic drops, and while the control group patients with mild exposure were treated with antibiotic drops only. The study group patients with moderate and severe exposure received combined treatment with bFGF and antibiotic drops, and after 2 months they were subjected to amniotic membrane transplantation, while the control group patients with moderate and severe exposure underwent amniotic membrane transplantation after using antibiotic drops. Observation of the growth of conjunctival epithelium and comparison of the healing rate of the two groups. RESULTS: The healing rates of the mild, moderate and severe exposure study group were 100% and 92.3%. The healing rates of the mild, moderate and severe exposure control group were 55.6% and 66.7% respectively. The difference of the healing rates of the mild exposure study group and the control group was significant (P=0.033). And the difference of the healing rates of the moderate and severe exposure study group and the control group was not significant (P=0.167). CONCLUSION: bFGF may promote obviously the healing of orbital implant exposure, particularly it can be the first choice for the treatment of mild degree exposure. For the moderate and severe cases, it can be administered before surgical repair to enhance neovascularization and will tend to increase the success rate of surgical repair. PMID- 17726743 TI - Preoperative localization and minimally invasive management of primary hyperparathyroidism concomitant with thyroid disease. AB - The coexistence of thyroid diseases with primary hyperparathyroidism (PHPT) can present a challenge in the clinical diagnosis and management for these patients. This study aims to determine the frequency of coexisting thyroid gland lesions in a consecutive series patients with PHPT, and to analyze the clinical features, diagnosis and treatment of these patients. Twenty-two cases of a total of 52 PHPT patients who had synchronous thyroid and parathyroid pathology were surgically managed in this study. Thirteen patients had ipsilateral thyroid nodules, and 9 patients had thyroid nodules in contralateral or bilateral side. Seven patients underwent direct parathyroidectomy and hemithyroidectomy via a mini-incision (about 3 cm), while other 15 procedures were converted to Kocher incision. Seventeen nodular goiter (32.7%), 2 thyroiditis (3.8%), 2 thyroid adenoma (3.8%) and 1 thyroid carcinoma (1.9%) coexisting with parathyroid adenoma were pathologically diagnosed. The sensitivity of preoperative ultrasonography (US) and methoxy-isobutyl-isonitrile (MIBI) scintigraphy for parathyroid lesions was 63.6% and 85.7%; and the overall positive predictive values for MIBI and US were 100% and 95.5% respectively. A high incidence of thyroid diseases that coexisted with PHPT in literatures was briefly reviewed. Our study illustrated the need for clinical awareness of concomitant PHPT and thyroid disease. A combination of US, computed tomography (CT) and MIBI scintigraphy would be recommended for preoperative localization of enlarged parathyroid adenoma and for evaluation of thyroid lesions. Synchronous treatment of associated thyroid abnormalities is desirable, and open minimally invasive surgical approach with additional resection of isolated ipsilateral thyroid nodules is possible in some of these patients. PMID- 17726744 TI - Induction of experimental acute ulcerative colitis in rats by administration of dextran sulfate sodium at low concentration followed by intracolonic administration of 30% ethanol. AB - Several models of experimental ulcerative colitis have been reported previously. However, none of these models showed the optimum characteristics. Although dextran sulfate sodium-induced colitis results in inflammation resembling ulcerative colitis, an obvious obstacle is that dextran sulfate sodium is very expensive. The aim of this study was to develop an inexpensive model of colitis in rats. Sprague-Dawley rats were treated with 2% dextran sulfate sodium in drinking water for 3 d followed by an intracolonic administration of 30% ethanol. The administration of 2% dextran sulfate sodium followed by 30% ethanol induced significant weight loss, diarrhea and hematochezia in rats. Severe ulceration and inflammation of the distal part of rat colon were developed rapidly. Histological examination showed increased infiltration of polymorphonuclear leukocytes, lymphocytes and existence of cryptic abscesses and dysplasia. The model induced by dextran sulfate sodium at lower concentration followed by 30% ethanol is characterized by a clinical course, localization of the lesions and histopathological features similar to human ulcerative colitis and fulfills the criteria set out at the beginning of this study. PMID- 17726745 TI - Identification of a high frequency of chromosomal rearrangements in the centromeric regions of prostate cancer patients. AB - The aim of the present investigation was to study the major chromosomal aberrations (CA) like deletion, translocation, inversion and mosaic in prostate cancer patients of Tamilnadu, Southern India. Totally 45 blood samples were collected from various hospitals in Tamilnadu, Southern India. Equal numbers of normal healthy subjects were chosen after signing a consent form. Volunteers provided blood samples (5 ml) to establish leukocyte cultures. Cytogenetic studies were performed by using Giemsa-banding technique and finally the results were ensured by spectral karyotyping (SKY) technique. In the present investigation, major CA like deletion, translocation, inversion and mosaic were identified in experimental subjects. Results showed frequent CA in chromosomes 1, 3, 5, 6, 7, 9, 13, 16, 18 and X. In comparison with experimental subjects, the control subjects exhibited very low levels of major CA (P<0.05). In the present study, the high frequency of centromeric rearrangements indicates a potential role for mitotic irregularities associated with the centromere in prostate cancer tumorigenesis. Identification of chromosome alterations may be helpful in understanding the molecular basis of the disease in better manner. PMID- 17726747 TI - Cloning, sequencing and expression analysis of the NAR promoter activated during hyphal stage of Magnaporthe grisea. AB - The promoter of NAR gene in Magnaporthe grisea was isolated and sequenced. The promoter sequences contained the "TATA" box, the "CAAT" box, and binding sites for fungal regulatory proteins. Programs that predict promoter sequences indicated that promoter sequence lies between locations 430 and 857 of the NAR promoter fragment. GFP expression under the NAR promoter and NAR transcript analysis revealed that this promoter is activated primarily at the mycelial stage in the rice blast fungus and could be used to express native or extrinsic genes in the mycelia of the rice blast fungus. PMID- 17726748 TI - Characterization of predominant bacteria isolates from clean rooms in a pharmaceutical production unit. AB - AIMS: To screen for the predominant bacteria strains distributed in clean rooms and to analyze their phylogenetic relationships. METHODS AND RESULTS: The bacteria distributed in air, surfaces and personnel in clean rooms were routinely monitored using agar plates. Five isolates frequently isolated from the clean rooms of an aseptic pharmaceutical production workshop were selected based on their colony and cell morphology characteristics. Their physiological and biochemical properties, as well as partial 16S rDNA sequences, were analyzed. Results showed that all the five isolates belong to Gram positive bacteria, of which three were Staphylococcus, one Microbacterium and one Bacillus species. Sensitivity tests for these bacteria isolates to 3 disinfectants showed that isolate F03 was obtuse, and had low susceptivity to UV irradiation, while isolates F02, F01 and F04 were not sensitive to phenol treatment. Isolates F04, F01 and F05 were resistant to chlorhexidine gluconate. CONCLUSION: Bacteria widely distributed in clean rooms are mainly a group of Gram positive strains, showing high resistance to selected disinfectants. SIGNIFICANCE AND IMPACT OF THE STUDY: Clean rooms are essential in aseptic pharmaceutical and food production. Screening bacteria isolates and identifying them is part of good manufacturing practices, and will aid in finding a more effective disinfection method. PMID- 17726746 TI - Cell therapy in congestive heart failure. AB - Congestive heart failure (CHF) has emerged as a major worldwide epidemic and its main causes seem to be the aging of the population and the survival of patients with post-myocardial infarction. Cardiomyocyte dropout (necrosis and apoptosis) plays a critical role in the progress of CHF; thus treatment of CHF by exogenous cell implantation will be a promising medical approach. In the acute phase of cardiac damage cardiac stem cells (CSCs) within the heart divide symmetrically and/or asymmetrically in response to the change of heart homeostasis, and at the same time homing of bone marrow stem cells (BMCs) to injured area is thought to occur, which not only reconstitutes CSC population to normal levels but also repairs the heart by differentiation into cardiac tissue. So far, basic studies by using potential sources such as BMCs and CSCs to treat animal CHF have shown improved ventricular remodelling and heart function. Recently, however, a few of randomized, double-blind, placebo-controlled clinical trials demonstrated mixed results in heart failure with BMC therapy during acute myocardial infarction. PMID- 17726749 TI - Effect of chlorogenic acid on antioxidant activity of Flos Lonicerae extracts. AB - Flos Lonicerae is a medically useful traditional Chinese medicine herb. However, little is known about the antioxidant properties of Flos Lonicerae extracts. Here the antioxidant capacity of water, methanolic and ethanolic extracts prepared from Flos Lonicerae to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and reduce Fe(3+) to Fe(2+) is examined. Chlorogenic acid, a major component of Flos Lonicerae, is identified and further purified from 70% ethanolic extract with high performance liquid chromatography (HPLC) and its antioxidant capacity is characterized. The total phenolic compounds and chlorogenic acid contents in Flos Lonicerae are determined. The present results demonstrate that the Flos Lonicerae extracts exhibit antioxidant activity and chlorogenic acid is a major contributor to this activity. PMID- 17726750 TI - Effects of alpha-tocopheryl acetate supplementation in preslaughter diet on antioxidant enzyme activities and fillet quality of commercial-size Sparus macrocephalus. AB - This study examined the effects of dietary alpha-tocopheryl acetate supplementation on antioxidant enzyme activities and fillet quality in commercial size Sparus macrocephalus. Three hundred fish [main initial weight (350+/-12) g] were divided into three groups (E250, E500 and E1000) and reared in 9 cages. The fish were fed for 8 weeks with three diets containing different levels of dietary alpha-tocopheryl acetate (289, 553, 1 069 mg/kg). Over the experimental period, fish were fed to satiation and reached a final mean weight of (465+/-28) g without significant body weight difference and proximate composition difference. Fillet alpha-tocopherol was significantly (P<0.05) different between groups, reaching levels of 14.2, 22.1, 30.9 microg/mg fillet for groups E250, E500 and E1000, respectively. Total serum superoxide dismutase (SOD) activity increased significantly (P<0.05) in fish fed the diets high in alpha-tocopheryl acetate, but serum glutathione peroxidase (GPX) activity was unaffected. In storage on ice, fillets of fish fed the diets high in alpha-tocopheryl acetate exhibited significantly lower (P<0.05) levels of oxidation. These results suggested that increased dietary alpha-tocopheryl acetate could increase its flesh deposition, increase the activity of SOD and prevent lipid peroxidation of Sparus macrocephalus fillets in retail storage on ice. PMID- 17726751 TI - In vitro assessment of gastrointestinal viability of two photosynthetic bacteria, Rhodopseudomonas palustris and Rhodobacter sphaeroides. AB - The objectives of this study were to assess the potential of two photosynthetic bacteria (PSB), Rhodopseudomonas palustris HZ0301 and Rhodobacter sphaeroides HZ0302, as probiotics in aquaculture. The viability of HZ0301 and HZ0302 in simulated gastric transit conditions (pH 2.0, pH 3.0 and pH 4.0 gastric juices) and in simulated small intestinal transit conditions (pH 8.0, with or without 0.3% bile salts) was tested. The effects of HZ0301 and HZ0302 on the viability and permeability of intestinal epithelial cell in primary culture of tilapias, Oreochromis nilotica, were also detected. All the treatments were determined with three replicates. The simulated gastric transit tolerance of HZ0301 and HZ0302 strains was pH-dependent and correspondingly showed lower viability at pH 2.0 after 180 min compared with pH 3.0 and pH 4.0. Both HZ0301 and HZ0302 were tolerant to simulated small intestine transit with or without bile salts in our research. Moreover, there was no significant difference (P>0.05) among three treatments including the control and the groups treated with HZ0301 or HZ0302 both in intestinal epithelial cell viability and membrane permeability, showing no cell damage. In summary, this study demonstrated that HZ0301 and HZ0302 had high capacity of upper gastrointestinal transit tolerance and were relatively safe for intestinal epithelial cells of tilapias. PMID- 17726752 TI - Biological activities of chamomile (Matricaria chamomile) flowers' extract against the survival and egg laying of the cattle fever tick (Acari Ixodidae). AB - In the present work, the potential of acaricidal activity of chamomile flowers' extract was studied against engorged Rhipicephalus annulatus tick under laboratory condition. For this purpose, the engorged females of Rhipicephalus annulatus were exposed to two-fold serial dilutions of chamomile flowers' extract (0.5%, 1.0%, 2.0%, 4.0% and 8.0%) using "dipping method" in vitro. The engorged ticks were immersed in different plant dilutions (five ticks for each dilution) for 1 min and they were immediately incubated in separate Petri dishes for each replicate at 26 degrees C and 80% relative humidity. Mortality rate for each treatment was recorded 5 d after incubation. The mortality rate caused by different dilutions of chamomile flower' extract ranged from 6.67% to 26.7%, whereas no mortality was recorded for non-treated control group. The mass of produced eggs varied form 0.23 g (in 8.0% solutions) to 0.58 g (in control), with no statistical differences between the treatments and control (P>0.05). Also the chamomile flowers' extract in highest concentration used (8.0%) caused 46.67% failure in egg laying in engorged females while non failure was observed for non treated control group. Macroscopic observations indicated that in effective concentrations of plant (4.0% and 8.0%), patchy hemorrhagic swelling appeared on the skin of treated ticks. The results presented for the first time in this study imply that chamomile may be considered as a promising plant for biocontrol of cattle fever tick disease in the field condition. PMID- 17726753 TI - Update on the CNS adverse effects of Sustiva (efavirenz). PMID- 17726754 TI - UNAIDS/WHO report highlights epidemic resurgence. PMID- 17726755 TI - Illinois enacts landmark law to promote expanded HIV testing. PMID- 17726756 TI - Disclosure. Testimony concerning victim's serostatus disallowed. PMID- 17726757 TI - Prisons. Dismissal denied over strip-search of HIV-positive prisoner. PMID- 17726758 TI - Registered sex offender prevails in HIV-testing challenge. PMID- 17726759 TI - Sentencing. Stiff sentence for HIV-positive crack user affirmed on appeal. PMID- 17726760 TI - A doctor talks about HPV vaccination. PMID- 17726761 TI - Psychogeriatric research comes of age in developing countries. PMID- 17726762 TI - Stability of the harm avoidance personality trait in late-life depression. PMID- 17726763 TI - Multiple system atrophy due to prolonged valproic acid treatment. PMID- 17726764 TI - The unspoken secret: sexual violence in World War II. PMID- 17726765 TI - The importance of the socioeconomic status of countries for mental disorders in old age: development of an epidemiological transition model. PMID- 17726766 TI - Does long-term economic adversity affect elderly suicide rates? A cross-national comparison. PMID- 17726767 TI - Depot risperidone in elderly patients: the experience of an Australian aged psychiatry service. PMID- 17726768 TI - The relationship between the Patient Generated Index (PGI) and measures of HR-QoL following diagnosis with head and neck cancer: are illness and treatment perceptions determinants of judgment-based outcomes? AB - OBJECTIVES: The primary objectives of this study were to examine the relationship between factors specified in the extended Self-Regulation Model (SRM) (illness and treatment perceptions and coping strategy) and three types of QoL outcome. Secondary objectives were to examine the relationships between outcome measures (general and cancer-specific HR-QoL and the Patient Generated Index (PGI)). DESIGN: Cross-sectional questionnaire study. METHODS: Eighty-two newly diagnosed patients with head and neck cancer (HNC) completed the Illness Perception Questionnaire--Revised (IPQ-R), the Beliefs about Medicines Questionnaire (BMQ), the Hospital Anxiety and Depression Scale (HADS), the Brief COPE and the Life Orientation Test (LOT-R). Patient outcomes were assessed using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, MOS Short Form Health Survey (SF-12v2) and the Patient Generated Index (PGI). RESULTS: These pre treatment cross-sectional results have shown that key components of the SRM (beliefs and coping) were explanatory factors of HR-QoL outcomes. The PGI was not associated with any of the components of the SRM. The PGI was partially correlated with HR-QoL measures; in particular, Global QoL/health status (EORTC) and Mental Component Summary scores (SF-12). CONCLUSIONS: Our findings suggest that the illness perceptions approach may be a useful method for eliciting and understanding patients' beliefs regarding HNC. In order to maximize outcomes, simple interventions could address particular patient beliefs and coping styles. PMID- 17726769 TI - Neutropenia in Felty's syndrome successfully treated with hydroxychloroquine. PMID- 17726770 TI - Season of birth and eating disorders: patterns across diagnoses in a specialized eating disorders service. AB - OBJECTIVE: In view of inconsistent findings from previous studies, the aim was to investigate possible seasonal variation in month of birth in patients with anorexia nervosa, bulimia nervosa, and eating disorder not otherwise specified. METHOD: We examined the month of birth in a cohort of 1,305 adult patients with a DSM-IV eating disorder diagnosis at first presentation to a specialized eating disorders service. RESULTS: When compared to general population data, we found no evidence of significant variation in month or season of birth in anorexia nervosa, bulimia nervosa, or eating disorder not otherwise specified. CONCLUSION: The authors question whether people who develop eating disorders differ from the general population in their season of birth. Caution is expressed about further speculation regarding the etiological significance of season of birth in eating disorders. PMID- 17726771 TI - The addition of a parent and clinician component to the eating disorder examination for children and adolescents. AB - OBJECTIVE: Our goal was to evaluate the addition of parent and clinician reports to the eating disorder examination (EDE) when used with children and adolescents. METHOD: The EDE was completed with 117 children and adolescents with eating disorders (mean age 14.95 +/- 1.91 years). A slightly modified version of the EDE was completed with parents, and clinician summary scores were assigned. Repeated measures analysis was used to compare child, parent, and clinician scores. RESULTS: In those 70 participants with anorexia nervosa (AN) or eating disorder not otherwise specified with a restrictive pattern (EDNOS-R), child scores were significantly lower than parent scores and clinician scores on restraint and weight concerns. On eating concerns and shape concerns, child scores were lower than clinician scores. Participants with bulimia nervosa (BN) or eating disorder not otherwise specified with binge eating or purging (EDNOS-BP), reported more restraint and shape concerns than parents (n = 47), but their scores did not differ from clinician ratings. No differences were seen in this group on weight concerns or eating concerns. CONCLUSION: Parent and clinician reports are particularly important when assessing children and adolescents with AN or EDNOS R, but may be less critical for those with BN or EDNOS-BP. PMID- 17726772 TI - Comments on seven novel mutations of the UGT1A1 gene in patients with unconjugated hyperbilirubinemia by D'Apolito et al. PMID- 17726773 TI - Nodular lesions of the liver in multiple myeloma. PMID- 17726775 TI - Mitral valve repair. PMID- 17726774 TI - Middle segment pancreatectomy: a useful tool in the management of pancreatic neoplasms. AB - Small, benign or low grade malignant tumours located in the neck of the pancreas are usually treated with enucleation. However if enucleation is too risky because of possible damage to the main pancreatic duct, standard pancreatic resections are performed. Such operations can lead to impaired long term exocrine-endocrine function. Middle segment pancreatectomy consists of a limited resection of the midportion of the pancreas and can be performed in selected patients affected by tumours of the pancreatic neck. Middle segment pancreatectomy is a safe and feasible procedure for treating tumours of the pancreatic neck; in experienced hands it is associated with no mortality but with high morbidity; the rate of "clinical" pancreatic fistula is about 20%. Moreover, it allows the surgeon to preserve pancreatic parenchyma and consequently long term endocrine and exocrine pancreatic function. PMID- 17726776 TI - Why is progress in treatment of cancer cachexia so slow? PMID- 17726777 TI - Pregnancy symptoms suggest low breast-cancer risk. PMID- 17726778 TI - Cetuximab for metastatic colorectal cancer. PMID- 17726779 TI - Bendamustine for advanced sarcoma. PMID- 17726780 TI - Predicting response to cisplatin in NSCLC. PMID- 17726781 TI - Nulliparity does not equal cancer. PMID- 17726782 TI - GnRH antagonist protects ovarian function. PMID- 17726783 TI - Antibody treatment for ovarian cancer. PMID- 17726784 TI - Immunotherapy holds promise for HRPC. PMID- 17726785 TI - Breast-cancer ultrasound instead of biopsy? PMID- 17726786 TI - Radioimmunotherapy for liver metastases. PMID- 17726787 TI - Toxic effects differ in combination treatment. PMID- 17726788 TI - Letrozole effective in ovarian cancer. PMID- 17726789 TI - Carcinogenicity of 1,3-butadiene, ethylene oxide, vinyl chloride, vinyl fluoride, and vinyl bromide. PMID- 17726790 TI - Massive air embolism in a newborn. PMID- 17726791 TI - Experts disagree over NICE's approach for assessing drugs. PMID- 17726792 TI - Therapy for autistic children causes outcry in France. PMID- 17726794 TI - Current awareness in human psychopharmacology. PMID- 17726793 TI - Criticism of the decision not to fund the HPV vaccine for pre-adolescent females in New Zealand, and response. PMID- 17726795 TI - Rosiglitazone + glimepiride: new drug. Another combination product to avoid. PMID- 17726796 TI - Epoetin: dose-dependent excess mortality. PMID- 17726797 TI - Meeting report: the sixth Interventional Workshop. PMID- 17726799 TI - Notice of retraction. PMID- 17726800 TI - Notice of retraction. PMID- 17726798 TI - Deep brain stimulation in patients with refractory temporal lobe epilepsy. AB - PURPOSE: This pilot study prospectively evaluated the efficacy of long-term deep brain stimulation (DBS) in medial temporal lobe (MTL) structures in patients with MTL epilepsy. METHODS: Twelve consecutive patients with refractory MTL epilepsy were included in this study. The protocol included invasive video-EEG monitoring for ictal-onset localization and evaluation for subsequent stimulation of the ictal-onset zone. Side effects and changes in seizure frequency were carefully monitored. RESULTS: Ten of 12 patients underwent long-term MTL DBS. Two of 12 patients underwent selective amygdalohippocampectomy. After mean follow-up of 31 months (range, 12-52 months), one of 10 stimulated patients are seizure free (>1 year), one of 10 patients had a >90% reduction in seizure frequency; five of 10 patients had a seizure-frequency reduction of > or =50%; two of 10 patients had a seizure-frequency reduction of 30-49%; and one of 10 patients was a nonresponder. None of the patients reported side effects. In one patient, MRI showed asymptomatic intracranial hemorrhages along the trajectory of the DBS electrodes. None of the patients showed changes in clinical neurological testing. Patients who underwent selective amygdalohippocampectomy are seizure-free (>1 year), AEDs are unchanged, and no side effects have occurred. CONCLUSIONS: This open pilot study demonstrates the potential efficacy of long-term DBS in MTL structures that should now be further confirmed by multicenter randomized controlled trials. PMID- 17726801 TI - [Adolf Zuppinger (1904-1991). Retrospective study of his life and work]. PMID- 17726804 TI - Australian migration policy of HIV-infected individuals requires renewed discussions. PMID- 17726803 TI - Clinical snapshot. Hypercalciuria and cystic calculi. PMID- 17726802 TI - Macular pigment measurements: which method should we use? PMID- 17726805 TI - A clinical study of transdermal contraceptive patch in Thai women. AB - OBJECTIVE: To study cycle control, compliance and safety of a transdermal contraceptive patch in Thai women. MATERIAL AND METHOD: Sixty-nine healthy women were assigned to receive 3 cycles of contraceptive patch (ethinyl estradiol 20 microg and norelgestromin 150 miccrog/day). All participants aged 18-45 years were invited to participate at the family planning clinic at King Chulalongkorn Memorial Hospital. Adverse effects, perceived advantages, and disadvantages were collected. RESULTS: The participants averaged 22.4 years old, height 158.9 cm, weight 52.5 kg, BMI 20.7. The most common location of patch application was abdomen and the most adverse event was application site reaction (29%) followed by breast tenderness, nausea vomiting, and headache. The breast symptom was mild in severity. The participants reported decrease in dysmenorrhea and shorter duration of bleeding. Only 1.1% had breakthrough bleeding. There were no significant changes in body weight and blood pressure. Improvement of their facial acne was reported. There were no pregnancies during the use and the adhesion of contraceptive patch was excellent, partial patch detachment was reported at only 14.4%. No complete patch detachment was found. CONCLUSION: The study found an overall positive impression of new transdermal contraceptive patch. Good compliance and few side effects were demonstrated. The adhesive of the contraceptive patch was excellent. PMID- 17726806 TI - A comparison of the efficacy of sublingual and oral misoprostol 400 microgram in the management of early pregnancy failure: a randomized controlled trial. AB - OBJECTIVE: To compare repeated doses of sublingual with oral misoprostol in the medical management of early pregnancy failure. MATERIAL AND METHOD: One hundred and thirty eight women with a period of gestation less than 20 week calculated by her last menstrual period and less than 12 weeks by size were sequentially allocated to two groups to receive either 400 microg of misoprostol orally or sublingually every 4 hours until termination of pregnancy was completed. RESULTS: There is no difference in the mean induction to abortion interval. Fever and chill were more common in sublingual group compared with oral group. The other adverse effects were similar and included nausea, vomiting, diarrhea, abdominal pain, and headache. CONCLUSION: Sublingual misoprostol is as effective as oral route. Most adverse effects are similar in both groups except fever was more common in sublingual group. PMID- 17726807 TI - A double blind randomized control trial, comparing effect of drospirenone and gestodene to sexual desire and libido. AB - BACKGROUND: Oral contraceptive is the most commonly used method of fertility control. Yasmin is a combination of a novel progestogen with anti-androgenic and anti-mineralcorticoid activities (3 mg Drospirenone (DRSP) and 30 microg ethinylestradiol (EE)). It has been shown in many clinical trials that Yasmin is an efficacious oral contraceptive, lacking undesired effects as with other oral contraceptives such as weight gain. However the effects of Yasmin on sexual desire and libido have not been intensively investigated so far OBJECTIVE: Investigate the effects of Yasmin on sexual desire, libido and changes in the free androgen index (FAI) compare to Meliane (75 microg gestodene + 20 microg ethinylestradiol). MATERIAL AND METHOD: The authors' report the results of a double blind randomized controlled study using a translated version of the Female Sexual Function Index questionnaire (FSFI) for the assessment of the sexual function. The free androgen index was calculated from measurements of testosterone and sexual hormone binding globulin. RESULT: The result shows statistically significant improvements regarding sexual desire, arousal and overall satisfaction in the Yasmin group. Additionally, an increased frequency of orgasms in the Meliane group was reported. Statistically significant differences between the two treatments regarding changes in the FSFI score and changes in the free androgen index have not been observed. CONCLUSION: The novel oral contraceptive containing drospirenone (Yasmin) and the non-anti-androgenic progestin containing oral contraceptive (Meliane) do not show unfavorable effects on sexual response and libido. PMID- 17726808 TI - Effect of hormone therapy on lipid profile in menopausal women. AB - OBJECTIVE: To study lipid profile of menopausal women with hormone therapy. MATERIAL AND METHOD: Two hundred and sixty eight menopausal women in good health conditions, separated into natural and surgical menopause group, received service at Menopausal clinic in Srinagarind Hospital, Faculty of Medicine, Khon Kaen University since 1996-2004. They regularly took a single type of hormone therapy for about 12 months and obtained blood cholesterol levels for pre- and post hormone therapy of about 12 months period. The data were analyzed with SPSS v. 10.0.5. RESULTS: The average age of the sample groups were 50.91 +/- 5.93 years and 52.83 +/- 5.28 respectively. Both sample groups have similar mean level of cholesterol levels during pretreatment period. Surgical menopausal group has greater HDL level than the naturally menopausal group with the average level of 64.24 +/- 15.32 mg/ dl. and 58.80 +/- 17.20 mg/dl. respectively. However after taking hormone therapy, blood cholesterol level was significantly changed in both groups. The mean level of LDL decreased (8.59% and 11.49% respectively) and mean level of HDL increased (15.43% and 6.89% respectively). CONCLUSIONS: Hormone therapy in menopausal women can improve cholesterol levels by decreasing LDL and increasing HDL with statistical significance (p < 0.05). PMID- 17726809 TI - Granulocyte-colony stimulating factors for secondary prevention of leucopenia in patients receiving chemotherapy. AB - OBJECTIVE: To evaluate the effectiveness of GCSF as a secondary preventive adjunct to chemotherapy in the gynaecologic cancer patients who previously had grade 3-4 neutropenia or leucopenia from chemotherapy. MATERIAL AND METHOD: We retrospectively reviewed the medical records of 94 chemotherapeutic cycles with GCSF as secondary prophylaxis in 29 patients with gynaecologic malignancy between January 1996 and April 2005. RESULTS: The median age of the patients was 51 years (21-75). Most of the patients had ovarian cancers (19 cases, 65.6%). From secondary GCSF, grade 4 neutropenia was developed in 12 of 94 cycles (12.8%), and grade 4 leucopenia was developed in 5 of 94 cycles (5.3%). There were no patients developing febrile neutropenia after GCSF support. CONCLUSION: Secondary GCSF prophylaxis was effective in preventing grade 4 leucopenia, grade 4 neutropenia, and febrile neutropenia. PMID- 17726810 TI - Increase accuracy of visual estimation of blood loss from education programme. AB - OBJECTIVE: To study the increase accuracy of visual estimation of blood loss after an education program. MATERIAL AND METHOD: Seven simulated scenarios with known measured amount of blood were created by using expired packed red cell from blood bank and common surgical materials. Ninety nurses were randomized into two groups. The experimental group attended blood loss estimation course while the control group did not. The percentage of errors in blood loss estimation were calculated and compared between both groups. The main outcome of this study was percentage of nurses who had accurate estimation. We assumed that if the estimated blood volume is within twenty percentage of actual volume it is accurate. RESULTS: There were no difference in age group (p = 0.08), clinical experiences (p = 0.95) and type of work (p = 0.47) between both groups. Educational program significantly increase accuracy in blood loss estimation (p < 0.05) in all seven scenarios. CONCLUSION: Educational program increased the accuracy of visual estimation of blood loss. PMID- 17726811 TI - Intrapartum fetal abdominal circumference by ultrasonography for predicting fetal macrosomia. AB - OBJECTIVE: To evaluate the diagnostic value of sonographic measurement of fetal abdominal circumference (AC) for the prediction of fetal macrosomia. MATERIAL AND METHOD: A prospective clinical trial was conducted at Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. The study consisted of 361 singleton pregnant women who were admitted for delivery at labor room. All women underwent sonographic measurements of the fetal abdominal circumference (AC) during the early intrapartum period. The AC values were correlated to actual fetal birth weight. The cut-off value of AC for predicting of fetal macrosomia was analyzed. RESULTS: Among 361 cases, the mean maternal age was 29.0 +/- 5.5 years (range, 15-46). The median gestational age was 39 weeks (range, 31-42). The mean fetal birth weight was 3,179.83 +/- 450.91 gm (range, 1,180-4,560). The prevalence of macrosomia was 11.08% (40/361). A cut-off value of abdominal circumference > or = 35 cm was the best predicting of fetal macrosomia. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 87.50%, 84.74%, 85.04%, 41.67%, and 98.19%, respectively. CONCLUSION: The intrapartum fetal AC measurement was useful in predicting of fetal macrosomia. An AC measurement of > or = 35 cm was the best value of fetal macrosomia prediction. PMID- 17726812 TI - Maternal height and the risk of cesarean delivery in nulliparous women. AB - OBJECTIVES: To evaluate the relationship between maternal height of < 155 cm and the risk of caesarean delivery due to cephalo-pelvic disproportion (CPD) among nulliparous women. DESIGN: Retrospective cohort study MATERIAL AND METHOD: A total of 660 term (GA > or = 37 weeks), uncomplicated singleton nulliparous pregnant women were enrolled on admission to labour room. The patients were divided into two groups based on maternal height, < or = 155 cm (440 cases) as control and < 155 cm (220 cases) as study group. The medical records of these women were reviewed. Various baseline clinical characteristics were collected. Intrapartum characteristics and maternal and neonatal outcomes were recorded. RESULTS: The rate of caesarean section of all indications was only slightly higher among study group than control group (16.4% and 13.7% respectively, p = 0.514). No significant difference was observed in the rate of caesarean delivery due to CPD (7.3% and 10.5% in control and study group respectively, p = 0.376). The rate of caesarean delivery due to CPD was highest among those with height < 150 cm (p < 0.001). Mean birth weight was significantly lower among study group than control group (2,927.7 +/- 368.1 g and 3,068.4 +/- 358.5 g respectively, p < 0.001). Low birth weight (< 2,500 g) was significantly higher among study group than control group (10.9% and 3.2% respectively, p < 0.001). CONCLUSION: Term singleton nulliparous pregnant women with maternal height < 155 cm were not associated with a greater likelihood of caesarean section for CPD. However, mean birth weight was significantly lower and low birth weight was significantly increased among mothers with short stature. PMID- 17726813 TI - Prevalence of gestational diabetes mellitus (GDM) in pregnant women aged 30 to 34 years old at Phramongkutklao Hospital. AB - OBJECTIVE: To assess the prevalence of GDM in pregnant women aged 30 to 34 years old who were screened by glucose challenge test (GCT) at Phramongkutklao Hospital. MATERIAL AND METHOD: The cross-sectional data were collected from 1332 pregnant women aged between 30-34 years who attended the antenatal care clinic and delivered at Phramongkutklao Hospital from March, 2003 to January, 2005. The 564 pregnant women aged between 30-34 years old who joined the project were tested by GCT at the gestational age of 24-28 weeks. If the level of blood sugar was the abnormal results, 100-g, 3-hour oral glucose tolerance test (OGTT) would be conducted. All relevant data including demographic information, risks factor for GDM, GCT and OGTT results and pregnancy outcomes were collected for further statistical analysis. RESULTS: There were 1332 pregnancies enrolled into the study. The 564 pregnant women were eligible for GCT with 228 positive results. Thirty-two cases of GDM were detected with the prevalence of 5.7%. In the GDM group, percentage of the common risk factors were family DM (28.1%) glucosuria (12.5%). Furthermore, only one case of premature rupture of membrane and one case of pregnancy-induced hypertension were found. Preterm labor, LGA, SGA, birth asphyxia, fetal anomalies and cesarean section were observe in 3.1%, 9.4%, 0%, 0%, 0%, and 40.6% respectively CONCLUSION: The prevalence rate of GDM in pregnant women aged 30-34 years old screened by GCT at Phramongkutklao Hospital is 5.7%. The GDM class A1 were 23 cases (4.1%) and GDM class A2 were nine cases (1.6%). Their impact on obstetric complication and pregnancy outcome was inconclusive due to the small number of cases. PMID- 17726814 TI - Sexuality after total abdominal hysterectomy in Srinagarind Hospital. AB - OBJECTIVE: To determine the effects on sexuality after Total Abdominal Hysterectomy (TAH) in north-eastern Thai women. DESIGN: Prospective descriptive study. SETTING: Srinagarind Hospital, Faculty of Medicine, Khon Kaen University from December 2004 to May 2006. MATERIAL AND METHOD: 80 married women, equal or less than 45 years old, which indicated for TAH with or without unilateral salpingo-oophorectomy. All patients had to attend the first questionnaire before surgery. The second and third questionnaires would be collected by mail in 3 and 6 months after surgery. MAIN OUTCOME MEASURES: Frequency of dyspareunia, sexual desire, coitus, masturbation, and the quality of sexuality after TAH. RESULTS: The frequency of dyspareunia was decreased from 91.25% before TAH to 5% in 6 months after TAH (95% CI 1.19-1.61, p < 0.05). The frequency of sexual desire was increased from 55% before TAH to 88.75% in 6 months (95% CI 0.22-0.61, p < 0.05). The frequency of coitus was increased from 38.75% before TAH to 96.25% in 6 months after TAH (95% CI 0.54-0.98, p < 0.05). Normal sexual relations were increased from 53.8% before TAH to 85% in 6 months after TAH (95% CI 0.20-0.47, p < 0.05). CONCLUSION: Sexuality was significantly improved overall after TAH and these might be the strong positive effects of TAH on sexual function. PMID- 17726815 TI - The incidence and complications of teenage pregnancy at Chonburi Hospital. AB - OBJECTIVE: This study aimed to determine the incidence of teenage pregnancy and compare obstetric and neonatal complications of teenage mothers with adult mothers. MATERIAL AND METHOD: This is a retrospective study conducted at the Department of Obstetrics and Gynecology, Chonburi Hospital, Thailand. The study group consisted of primigravida women aged 13-20 years who gave birth at Chonburi Hospital from 1 January 2000 to 31 December 2005. The control group consisted of primigravida women aged 20-25 years who gave birth during the same period. Demographic, obstetric, and neonatal complications information were collected and compared between the study and control groups. RESULTS: The study group consisted of 2,490 women and the control group consisted of 3,909 women. The study found that incidence of teenage pregnancy at Chonburi Hospital was 90 cases per 1,000 mothers. The study group had a lower gestational age at delivery than the control group and a higher preterm delivery rate (20.1% vs 13.9%, p < 0.001). The study group had more inadequate antenatal care than control group (25.9% vs 13.4%, p < 0.001). Vaginal delivery was the major route of delivery in study group. Anemia was a significant difference between the study and control groups (17.1% vs 11.1%, p < 0.001). Low birth weight infant rate in study group was higher than control group significantly. CONCLUSION: The incidence of teenage pregnancy was found to be 9%. Teenage mothers had lower levels of education and higher levels of inadequate antenatal care. Preterm labour and anemia were the obstetric complications in the teenage pregnancy. Low birth weight was the only neonatal complication in teenage pregnancy in the study. PMID- 17726816 TI - The use of levonorgestrel - IUD in the treatment of uterine myoma in Thai women. AB - OBJECTIVE: This study was designed to evaluate the potential usefulness of the levonorgestrel-releasing intrauterine device (LNG - IUD ; Mirena) in treating women with uterine myomas. DESIGN: Prospective before-and-after (comparing) study. SETTING: Department of Obstetrics and Gynecology King Chulalongkorn Memorial Hospital. SUBJECTS: Sixteen women with uterine myomas who intended to receive treatment with the LNG IUD. INTERVENTION(S): Clinical and ultrasound examinations were performed prior to and at 1, 3 and 6 months after the LNG IUD insertion. MAIN OUTCOME MEASURES: Myoma and Uterine volume, menstrual blood loss assessed with pictorial blood loss assessment charts and hematocrit. RESULTS: Use of the LNG IUD was associated with a statistically significant reduction in the total myoma volume, average uterine size and marked reduction in menstrual blood loss. After 6 months of use, the median total myoma volume decreased from 19.82 mL to 11.63 mL (p < 0.05), median pictorial blood loss assessment chart score declined from 89 to 3 (p < 0.05). Hematocrit level increased over 6 months of use. The most common side effects were bleeding disturbances (68.8%). No pregnancies occurred during the study. CONCLUSION: The LNG IUD was associated with a profound reduction in myoma and uterine volume. For women with myomas of this size, the LNG IUD provides effective medical treatment of bleeding. PMID- 17726817 TI - Validation of risk scoring scheme for cesarean delivery due to cephalopelvic disproportion in Lamphun Hospital. AB - OBJECTIVE: To validate the risk scoring scheme for cesarean delivery due to cephalopelvic disproportion in Lamphun Hospital. MATERIAL AND METHOD: A case control study was conducted between January 1st, 2005 and April 30th, 2006, including, prospectively collected, 132 women who had cesarean delivery due to cephalopelvic disproportion (CPD) as cases and 394 women who delivered by normal labor as controls. Cases and controls were evaluated for risk scores, the scoring scheme of which had previously been developed. The prediction by the risk score was tested with an area under the receiver operating characteristic (ROC) curve of a logistic regression. Another independent set of obstetric cases referred form community hospitals in Lamphun were also evaluated for the risk scores. RESULTS: The risk scores explained 84.5% of the probability of CPD as demonstrated by the area under the ROC curve. The scores of pregnant women referred from rural hospital underwent cesarean delivery were higher than those with vacuum extraction and with normal delivery (mean = 9.2 +/- 2.4, 7.5 +/- 3.2 and 6.4 +/- 2.3 respectively). The score of cesarean delivery was significantly higher than normal delivery (p < 0.001) while the score of vacuum extraction was in between and only slightly higher (p = 0.116). CONCLUSION: Risk scores obtained form this scoring scheme predicted cesarean delivery with high precision. The scores also discriminated cesarean deliveries from normal deliveries among cases referred from community hospitals. Community hospitals may gain benefit by adopting this simple scoring scheme into their practices. PMID- 17726819 TI - Silver-coated dressing market booms as manufacturers 'jump on bandwagon'. PMID- 17726818 TI - Ion channels: new targets for the next generation of tocolytics agents. AB - Ion channels are interesting molecules since they mediate not only uterine contraction but also uterine relaxation. We have examined the expression, function, and correlation between the large conductance calcium-activated potassium (BKCa) channel, beta2 adrenoceptor (AR), and long-lasting (L) type calcium (Ca2+) channel. These are the main channels and receptor that are involved in the uterine contraction/ relaxation process. Our evidence has shown that BKCa channel is closely correlated with beta2 AR in mediating uterine relaxation. Both proteins are situated in close proximity on the plasma membrane of human myometrium and are downregulated approximately 50% after the onset of labor. Interestingly, L type Ca2+ channel, which involves in the contraction pathway, seems to be in the same compartmentation as BKCa channel/ beta2 AR macromolecular complex. Further studies are now being conducted to identify the signaling complex components that could potentially be a target for new tocolytic agents. PMID- 17726820 TI - [Metformin-related lactic acidosis in an 85-year-old woman]. PMID- 17726822 TI - [Critical remarks regarding guidelines based on scientific research]. PMID- 17726821 TI - [Metformin-related lactic acidosis in an 85-year-old woman]. PMID- 17726823 TI - [Dr. Olga Zavate{December 16, 1927-January 23, 2000}. Member of the Romanian Medical Academy]. PMID- 17726824 TI - Updating the prostate cancer guidelines. PMID- 17726825 TI - Toward the development of an inventory of daily widowed life (IDWL): guided by the dual process model of coping with bereavement. AB - The Dual Process Model of Coping with Bereavement (M. Stroebe & H. Schut, 1999) suggests that the most effective adaptation involves oscillation between 2 coping processes: loss-orientation (LO) and restoration-orientation (RO). A 22-item Inventory of Daily Widowed Life (IDWL) was developed to measure these processes and the oscillation between them and assessed by examining 163 bereaved widow(er)s, ages 45-94 years. The LO and RO subscales produced alpha coefficients of .90 and .79, respectively. The more recently widowed demonstrated a high degree of oscillation balance between the two processes, while there was a greater emphasis on restoration-orientation among those bereaved longer. Both subscales generated significant relationships with the bereavement outcome measures used in this study. Furthermore, restoration-orientation was directly related to the level of self-care and daily living skills as well as personal growth. We identify six dimensions of oscillation that warrant further consideration and encourage others to help develop and refine all features of the IDWL and make it adaptable to other loss relationships. PMID- 17726826 TI - Beyond the evidence: is there a place for antidepressant combinations in the pharmacotherapy of depression? PMID- 17726827 TI - Resistance to viral infection of super p53 mice. AB - Induction of expression of the tumor suppressor p53 after interferon treatment has been recently demonstrated (Takaoka et al., 2003), suggesting an antiviral activity of the protein. In addition, a direct correlation between p53 levels and tumor resistance has been addressed by generating mice with an extra copy of p53 ('super p53' mice) (Garcia-Cao et al., 2002). Here, we show that vesicular stomatitis virus replication in mouse embryo fibroblasts derived from 'super p53' mice is impaired as a result of apoptosis induction via p53 activation. These findings unequivocally demonstrate an antiviral activity of p53, a process that may contribute to inhibit the spread of the virus in vivo. PMID- 17726828 TI - The (re)construction of self after the death of a partner to HIV/AIDS. AB - The aim of this study was to explore individuals' self-construals after the loss of a partner from HIV/AIDS for whom they were a caregiver. Seven gay or transsexual bereaved caregivers were interviewed after the death of their partners. The data revealed patterns suggestive of A. Aron and E. N. Aron's (1986) "inclusion of others in the self" (IOS) with partners described as part of participants' identity. Using the metaphor of the IOS, the results illustrate how care-giving became a part of the self as well as aspects of the partner. Upon the death of the partner, the loss resulted in a crisis of meaning due to the loss of the person and relationship that had contributed significance and purpose to life. Regaining meaning involved making sense of both the relationship and the care-giving role. PMID- 17726829 TI - Death anxiety across the adult years: an examination of age and gender effects. AB - Two studies examined death anxiety across the adult years. In the first study, 304 men and women between 18 and 87 years completed the Collett-Lester Fear of Death scale. Death anxiety peaked in both men and women during their 20s and declined significantly thereafter. However, women displayed a secondary spike during their 50s not seen in men. In the second study, 113 women between 18 and 85 years completed the Templer Death Anxiety Scale. Death anxiety displayed the same bimodal distribution and significant decline with age seen in Study 1. The results suggest that more emphasis should be placed on the cause of increased death anxiety among 20-year-olds and on why women, but not men, experience a second anxiety spike during their 50s. PMID- 17726830 TI - Health care professionals' death attitudes, experiences, and advance directive communication behavior. AB - The study surveyed 135 health care professionals (74 nurses, 32 physicians, and 29 social workers) to examine their personal death attitudes and experiences in relation to their reported advance directive communication practice behavior. Negative correlations were found between collaborating with other health care professionals regarding the directives and fear of death, avoidance of death, and escape acceptance of death. Approach acceptance of death positively correlated with initiating the discussion of advance directives. Practitioners indicating recent personal experiences with terminal illness reported disclosing more information about the documents. PMID- 17726831 TI - An exploration of gender differences on the reasons for living inventory among older adults. AB - This study evaluated gender differences on the Reasons for Living Inventory (RFL) specifically among older adults, a population known to have the highest suicide rate among all age groups, with older men being disproportionately at risk. Community-dwelling women (n = 175; M age = 69.0 years; 81% Caucasian) and men (n = 145; M age = 69.5 years; 76% Caucasian) completed the RFL. Results showed no significant gender differences on the RFL subscales and the total score. The rank order of the subscales was also the same for older men and women. An implication of these findings is that the robust gender differences on the RFL found among younger individuals appear to diminish with advancing age, although it is unclear to what extent older men improve in the reasons for staying alive or older women decline in their reasons for staying alive. PMID- 17726833 TI - Why I'm a reluctant rapid responder. PMID- 17726832 TI - Treatment Options for HIV-Associated Tuberculosis. AB - The vicious interaction between the human immunodeficiency virus (HIV) infection and tuberculosis (TB) pandemics poses special challenges to national control programs and individual physicians. Although recommendations for the treatment of TB in HIV-infected patients do not significantly differ from those for HIV uninfected patients, the appropriate management of HIV-associated TB is complicated by health system issues, diagnostic difficulties, adherence concerns, overlapping adverse-effect profiles and drug interactions, and the occurrence of paradoxical reactions after the initiation of effective antiretroviral therapy. In this article, recommended treatment strategies and novel approaches to the management of HIV-associated TB are reviewed, including adjuvant treatment and options for treatment simplification. A focused research agenda is proposed in the context of the limitations of the current knowledge framework. PMID- 17726834 TI - Joy of rapid responses. Readers read articles more closely when they can respond. PMID- 17726835 TI - Iron metabolism. PMID- 17726836 TI - The chromium mechanism. PMID- 17726838 TI - Proton-decay experiments. PMID- 17726837 TI - Mathematicians and science. PMID- 17726839 TI - The culinary alchemy of eggs. PMID- 17726840 TI - Panoramic photographs. PMID- 17726841 TI - Tree architecture. PMID- 17726842 TI - Gravitational lenses. PMID- 17726843 TI - Acoustic fluidization. PMID- 17726844 TI - Sexual selection and red-winged blackbirds. PMID- 17726846 TI - Marginalia. Statistical odds and ends. PMID- 17726845 TI - Electron microscopy of minerals. PMID- 17726847 TI - Clinical snapshot. Lethargy and emaciation in a dog. PMID- 17726848 TI - Computed tomography. PMID- 17726849 TI - Clinical snapshot. Cutaneous nodules in a cat. PMID- 17726850 TI - The use of lidocaine patches. AB - Our recent pharmacokinetic studies with lidocaine patches in dogs and cats have found that plasma concentration of lidocaine following patch application tends to be low. Lidocaine patch application can be a powerful analgesic adjunct to existing analgesic agents, including opioids and NSAIDs, in a multimodal pain management scheme. This article reviews the pros and cons of lidocaine patch application and its clinical use in dogs and cats. A comparison of lidocaine and fentanyl patches is included. PMID- 17726852 TI - Canine immune-mediated hemolytic anemia: treatment and prognosis. AB - The treatment of primary immune-mediated hemolytic anemia involves short-term oxygen-carrying support and long-term immunosuppressive therapy. Therapeutic options include blood transfusion, standard and more speculative immunosuppressive agents, splenectomy, and prevention of thromboembolic disease. This article also discusses the prognosis and prognostic indicators. PMID- 17726851 TI - Canine immune-mediated hemolytic anemia: pathophysiology, clinical signs, and diagnosis. AB - Immune-mediated hemolytic anemia (IMHA) is a common type of anemia in dogs and cats that results from a type II hypersensitivity reaction. The disease is most common in middle-aged female dogs, especially American cocker spaniels. The common clinical signs are associated with severe anemia and the resultant inflammatory response. There is no pathognomonic test for IMHA, but the following are suggestive of it: the presence of hemolytic anemia in a young adult or middle aged dog of a predisposed breed, autoagglutination and/or spherocytosis, positive results from a direct antiglobulin (Coombs') test, elimination of any other underlying cause of anemia, and an appropriate response to immunosuppressive therapy. PMID- 17726853 TI - Clinical snapshot. A vulvar mass in a dog. True hermaphrodite. PMID- 17726854 TI - Understanding cats. PMID- 17726855 TI - [Fatigue]. PMID- 17726856 TI - [New concept in the treatment of the pilonidal sinus]. AB - Symptomatic pilonidal sinus is characterized by an acute or a chronic inflammation. The surgical management of symptomatic pilonidal sinus is still a matter of discussion and no clear recommendations exists. On the basis of results from published studies and our own experience we developed a new two step therapy concept: Infected pilonidal were first drained by a small excision of the abscess (if possible in local anesthesia) followed by a close fistula excision. With this approach we were able to achieve a low morbidity and a high healing rate. In the case of extensive fistulating pilonidal sinus or recurrent disease we recommend radical excision and primary reconstructive flap what showed good aesthetic results. PMID- 17726857 TI - [Uterine tumor resembling ovarian sex cord tumor: case report and review of literature]. AB - Uterine tumours with sex cord-like differentiation are rare. They are observed, pre- and post-menopausal women between the fourth and the sixth decade and manifest themselves by haemorrhagic anomalies and usually enlarged uteri, misinterpreted as uterus myomatosus. One distinguishes between two groups on account of the share of sex cord-like elements, i.e. tumours with only focal sex cord-like differentiation with a tendency to relapses and metastatic spread, and tumours with predominant differentiation in the sense of ovarian sex cord tumours with a good prognosis because surgical treatment alone often leads to relapse free survival. Because of the tumours' rarity, there are no randomized studies as to an optimal therapy. Since there have been reports on endometrial stromal sarcoma with low malignant potential in adjuvant therapy of breast cancer with Tamoxifen, one can assume that this entity will occur more frequently in future. PMID- 17726858 TI - [Myositis with pulmonary fibrosis and eosinophilia]. AB - A 74-year old female patient suffered from dyspnoea, subfebrile body temperature, myalgias, arthralgias and presented a transitory skin rash. Further findings were an eosinophilia, synovitis, a myositis and pulmonary fibrosis. There was no evidence for a malignancy or an infectious disease. We diagnosed an Anti-Jo-1 Syndrome with a secondary Sjoegren syndrome. Immunsuppressive therapy with steroids, later in addition methotrexate led to improvement of the patient's clinical condition. Above mentioned symptoms and its differential diagnosis are discussed in this article. PMID- 17726859 TI - [The physicians' art column]. PMID- 17726861 TI - [Gastrointestinal stromal tumors (GIST)]. AB - Gastrointestinal stromal tumors (GIST) are the example of very rare sarcoma of alimentary tract. In the presented material, 5 cases of GIST were diagnosed and treated in our Department. One tumor was localized in stomach, two in rectum and one in jejunum. Primal localization of the last tumor was not discovered. It was visualized between rectum and bladder, covered by the omentum. In each case confirmation of the diagnosis was done on the basis of the immunohistochemical staining--CD117(+). In four cases surgery was the primary treatment. Only in one case radical resection was performed. In other three cases radical resection was not possible due to the presence of liver metastases (in two cases) and the size of the tumor (20 x 10 cm). One patient was disqualified from the surgical treatment. Four patients were qualified for the chemotherapy with imatinib. In one case, patient did not undergo the treatment. In the group treated with imatinib the early reply was satisfactory. On the ground of our material we conclude that patients usually begin the treatment in the advanced stage of the disease. When the GIST diagnosis is probable, one has to broaden the histopathological examination with immunohistochemical staining for CD117 antigen. Making the right diagnosis is crucial for patients, since imatinib is effective even in the advanced stages of the disease. Nevertheless radical surgical treatment is still the primary choice for the patients with GIST. PMID- 17726860 TI - [The study of the prevalence of depressive disorders in primary care patients in Poland]. AB - Studies performed in recent years in different countries suggest a considerable prevalence of depressive disorders in primary care patients. The aim of our study was the assessment of depressive disorders among primary care patients in Poland. MATERIAL AND METHODS: Three-hundred thirty-three randomly chosen private and public primary care clinics from the whole country took part in the study. In each centre, 20 or 25 patients aged 18-65 years coming for a regular visit were asked to participate in the study. All patients filled in the Beck Depression Inventory (BDI). Additionally, basic demographic data and information on the presence of chronic somatic diseases were collected. Those patients who scored 12 or more points on BDI (cut-offpoint for depression in Poland) were evaluated by a primary care physician for presence of a depressive disorder upon the ICD-10 criteria and subsequently referred for a psychiatric consultation to the nearest psychiatric outpatient clinic for establishing plausible diagnosis of depression. RESULTS: Out of 7360 patients approached, 7289 (95.5%) agreed to participate. The mean age of the sample was 43.3 +/- 13.2 and 71% were females. Forty one percent of patients (2985) had 12 or more points on the BDI and were referred for a psychiatric evaluation. Only half of them came for a psychiatric consultation. Depressive disorder was recognised in 906 patients. Estimated prevalence of depressive disorders in the whole sample was 23.3%. The patients in whom depressive disorders were confirmed by psychiatric assessment had significantly more often hypertension, ischaemic heart disease, anaemia, stroke and hypothyroidism. CONCLUSIONS: The results obtained show that depressive disorders' prevalence in primary care patients in Poland is significant. The patients who had depressive disorders significantly more often than patients without depression suffered from some somatic diseases. In light of the results, both recognition and adequate treatment of depressive disorders in primary care patients should be regarded as equally important as the recognition and treatment of cardiovascular diseases or other common somatic illnesses. PMID- 17726862 TI - [Serum levels of vascular endothelial growth factor in chronic hepatitis C patients treated with interferon alpha and ribavirin]. AB - Liver fibrosis is a result of disturbed balance between extracellular matrix protein synthesis and degradation. Growth factors may play the meaningful role in pathogenesis of fibrosis. The aim of the study was the assessment of VEGF role in pathogenesis of fibrosis associated with chronic hepatitis C (CHC) and evaluation of the influence of antiviral therapy on VEGF levels depending on treatment results. MATERIAL AND METHODS: Study group included 100 CHC patients with fibrosis (Scheuer: 1-4 points). Control group included 30 HCVAb-positive subjects with normal ALT, without fibrosis (Scheuer: 0 points). From all subjects blood samples were taken at the beginning of the study. From study group patients blood samples were also collected after the treatment with Rebetron. RESULTS: There was no significant difference in VEGF levels between CHC group and control group. Significant negative correlation between VEGF levels and inflammatory activity (R = -0.40; p < 0.01) and fibrosis stage (R = -0.30; p < 0.05) was observed. After antiviral treatment significant elevation of VEGF occurred in responders (112.8 vs. 315.03 pg/ml; p < 0.05), but not in non-responders. CONCLUSIONS: 1. Progression of liver lesions is correlated with reduction of VEGF levels. 2. Good therapeutic effect is connected with the elevation of VEGF levels. 3. Angiogenesis stimulation by VEGF probably is an important element in regenerative processes accompanying fibrosis regression. PMID- 17726863 TI - [The usefulness of P300 potential in hepatic encephalopathy diagnostics of alcoholic etiology]. AB - The consequence of consuming excessive amount of alcohol is the damage of internal organs, particularly liver. In the liver there comes in turn to its fatty degeneration, hepatitis, fibrosis and finally to its cirrhosis. The aim of the study was the analysis of P300 potential in subjects chronically abusing alcohol with alcohol-related toxic liver damage and the assessment of the usefulness of this potential in the diagnosis of hepatic encephalopathy. MATERIAL AND METHODS: Group I--consisted of 30 men meeting the criteria of alcohol dependency syndrome, with diagnosed alcohol-related toxic liver damage. Comparative group--consisted of 30 physically and mentally healthy men, with no alcohol dependency syndrome. The following were carried out in all the examined: examination of auditory endogenic P300 potential. RESULTS: In subjects chronically abusing alcohol, with diagnosed toxic liver damage statistically significant prolonged latency and also reduced amplitude (p < 0.001) were found in comparison with the control group. CONCLUSIONS: 1. Changes in P300 parameters (latency elongation and amplitude reduction) in alcohol-dependent subjects with alcohol-related liver damage were confirmed. 2. P300 potential may be a complementary method in the diagnosis of hepatic encephalopathy. PMID- 17726865 TI - [Hemostatic disturbances in chronic myeloid leukemia]. AB - Chronic myeloid leukemia (CML) is one of the chronic myeloproliferative disorders. Haemostatic disturbances and infections are the main causes of death in CML. MATERIAL AND METHODS: We investigated 22 patients with CML aged 38-55 years (median 45.0). Twenty nine healthy controls were sex and age-matched. Patients underwent following examination: whole blood count, blood smear, platelets count, prothrombin time (PT), activated partial thromboplastin time (aPTT), euglobulin lysis time (ELT), fibrin degradation products (FDP), thrombin antithrombin complexes (TAT), plasmin-alpha2-antiplasmin complexes (PAP), antigen and urokinase plasminogen activators (t-PA:Ag, u-PA:Ag), antigen of tissue plasminogen activator inhibitors type 1 and 2 (PAI-1:Ag, PAI-2:Ag), fibrinogen concentrations, antitrombin (AT) and alpha2-antiplasmin (alpha2-AP) activity. RESULTS: TAT concentration (35.46 ng/ml) was significantly higher in examined group than in controls (3.41 ng/ml). Significantly higher fibrinogen concentration (3.31 g/l) and elevated platelet count (611.0 G/1) was observed in patients with CML. We also showed significantly higher concentrations of u-PA:Ag (0.67 ng/ml), PAI-1:Ag (34.8 ng/ml), PAP complexes (473.10 ng/ml) and FDP (17.10 microg/ml) in patients with CML. CONCLUSION: High TAT, fibrinogen concentrations and elevated platelet count in patients with CML are the evidences of an activation of coagulation. On the other hand fibrinolysis activation is proved by higher concentrations of u-PA:Ag, PAI-1:Ag, complexes PAP and FDP. PMID- 17726864 TI - [Prognostic significance of microvessel density in ovarian cancer]. AB - The antigen of endothelial cell which are the exponent of microvessels density in cancer tumor as CD31, CD34 and CD105 are the most common analysed markers of angiogenesis. The aim of the work was to analyse the expression of CD31, CD34 and CD105 antigens--three basic markers of microvessel density in ovarian cancer. MATERIAL AND METHODS: The material included 80 patients with ovarian carcinoma, treated between 1996 and 2001 in Department of Oncology Gynecology of Lower Silesian Centre of Oncology. The median of age was 54.4 years. Most of analyzed cases (n = 53) were serum ovarian carcinoma in III and IV FIGO stage. RESULTS: The correlations between microvessel density (MVD) and clinicopathological parameters were analyzed. We have stated that in patients younger than 50 years the microvessel density was lower. This correlation was statistically significant in the estimation of MVD by CD31 and CD34 expression and close to statistically significant by marked CD105 expression. In patients with time of menopause that occurred before 46 years of age, microvessel density marked with CD105 expression was significantly higher and close to significance in CD31 marker. CONCLUSIONS: Cox analysis proved that independent risk factors of death in patients with ovarian cancer were: age over 50 years, low degree of patient performance according to WHO (World Health Organization) scale, high FIGO (International Federation of Gynecology and Obstetrics) stage and high expression of CD34 microvessel density. PMID- 17726866 TI - [Cognitive dysfunction in patients with chronic obstructive pulmonary disease]. AB - The examination of cognitive function is not the part of the basic set of tests which is carried out in patients with chronic obstructive pulmonary disease (COPD). However there are some theoretical reports and sparse publications indicating the impairment of these functions among patients with COPD. These impairments are related to the patients with hypoxemia. In non-hypoxemic patients with COPD cognitive performance should be studied because of controversial reports. The influence of COPD on cognitive performance is partially reversible using oxygen therapy and/or physical activity which, in our opinion, is not appreciated enough. It seems that evaluation of cognitive performance with selected tests can be helpful in the assessment of severity of the disease. Moreover, it can be useful in estimation and prognostication of the self dependence degree as well as the patients life span. The use of such methodological tools as corresponding tests analyzing cognitive performance in patients with COPD could lead to better care. It could also minimize the risk of transition of mild cognitive impairment into dementia which results in significant quality of life deterioration. It appears that patients with present impaired cognitive performance with or without recognized dementia should remain under special care providing adequate treatment. We assumed that due to properly managed treatment it may be possible to retain the process of increasing cognitive impairment what would effect in long-term self-reliance. PMID- 17726867 TI - [Saliva as a main component of oral cavity ecosystem. Part I. Secretion and function]. AB - Results of studies over the recent years indicate that saliva is one of the most important factors which influence on the oral cavity homeostasis. Human saliva not only lubricates the oral tissues, making oral function such as speaking, eating, and swallowing possible, but also protects teeth and oral mucosa surface against influence of many harmful factors. Knowledge about saliva helps to understand pathomechanisms, to work out the prevention and treatment rules of oral cavity diseases. PMID- 17726868 TI - [Sudden death in competitive athletes]. AB - In athletes under the age of 35 years the incidence of sudden death is low, most causes to be due to ventricular arrhythmias, usually provoked by exertion, and nearly always occur in the presence of structural heart disease or abnormalities in the conduction system. The most common structural disease is hypertrophic cardiomyopathy followed by coronary artery anomalies, idiopathic dilated cardiomyopathy, arrhythmogenic right ventricular dysplasia, aortic stenosis, myocarditis, the Wolff-Parkinson-White syndrome, and long QT syndrome. The evaluation of athletes with symptoms of cardiac arrhythmias, syncope, family history of sudden death require a complete cardiac workup. If they have documented hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, idiopathic dilated cardiomyopathy, long QT syndrome, family history presentation with sudden death, and septal thickness greater than 20 mm competitive athletics are generally prohibited. In athletes with asymptomatic bradyarrhythmia, supraventricular tachycardias and atrial premature contractions without structural heart disease all competitive sports are allowed if heart rate in bradyarrhythmia appropriately increases with exercise. Athletes with premature ventricular contraction, nonsustained ventricular tachycardia and non structural heart disease are without athletic restriction as long as the arrhythmia does not worsen on exertion and cause dyspnea, presyncope or syncope. PMID- 17726869 TI - [Quality of life outcomes of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD)]. AB - Pulmonary rehabilitation is an important modality in the treatment of chronic obstructive pulmonary disease (COPD). In this review we introduce the terms of outcomes of the disease and of quality of life. We then review the effects of pulmonary rehabilitation on outcomes of COPD. We focus on the role of various modalities of pulmonary rehabilitation on improving the quality of life of patients with this condition. PMID- 17726870 TI - [Vasovagal syncope--standards of management, clinical and diagnostic problems]. AB - Although vasovagal syncope is the most frequent cause of loss of consciousness, the ability of diagnostic and therapy is still weak. The most important diagnostic method in vasovagal syndrome is the tilt test. The number of clinical trials of the effective treatment of vasovagal syncope is still small. This article attempts to summarize the most important clinical problems connected with vasovagal syncope and includes present guidelines of European Society of Cardiology. The treatment of vasovagal syndrome is mainly based on tilt training and non-pharmacological methods. Presently, there is a lack of evidence for the efficiency of pharmacological treatment. Cardiac pacing should be limited as a choice to a very small group of patients affected by severe cardioinhibitory type of vasovagal syndrome. PMID- 17726871 TI - [Clinical spectrum of neuroborreliosis]. AB - Lyme disease is a multisystem infectious disease with a wide variety of symptoms involving the skin as well as nervous, musculosceletal and cardiovascular systems. Lyme disease is caused by spirochaete Borrelia burgdorferi transmitted by Ixodes tics in endemic regions. The diverse manifestations of neuroborreliosis require it to be included in differential diagnosis of many neurological disorders. The paper reviews the spectrum of clinical symptoms of nervous system involvement in early and late Lyme disease. PMID- 17726872 TI - [The significance of neutrophil in inflammatory response after cardiac surgery with cardiopulmonary bypass]. AB - Cardiac surgery with cardiopulmonary bypass (CPB) can lead to postoperative complications like systemic inflammatory response syndrome (SIRS). These changes are associated with a risk of postoperative organ dysfunction and increased morbidity and mortality in the postoperative period. Its etiology is not yet clarified in details, but this thought to be of immunologic origin. The exact knowledge of these reactions is crucial for the selection of treatment strategies. Cardiac surgery induces neutrophil activation, degranulation and endothelial dysfunction. The nature of the participation of the neutrophil and its time course in the post CPB inflammatory response remains controversial. The aim of this work is to review state-of-the-art knowledge about neutrophil and the role of this cell as a regulator of immune response after cardiovascular surgery. PMID- 17726873 TI - [Lasers in plastic surgery--vascular lasers]. AB - Laser treatment of the cutaneous vascular lesions gained approbation and well established position among plastic surgery techniques. Rapidly evolving laser market delivers us modem and safer devices. In the paper we discuss the most common vascular lesions and available lasers used to treat them. Described indications and safety rules might be useful for many specialists for their patient therapy choice. PMID- 17726874 TI - [Hemostatic disturbances in obesity]. AB - Overweight and obesity belong to the group of chronic diseases in which there is a substantially increased risk of thromboembolic incidents. The changes involve both arterial and venous system. The decisive role in their development seems to have disorders ofhemostasis including both excessive activation of coagulation system and/or inhibition of fibrinolysis. Coagulation changes in obese persons are complex. They include, among others, increase in concentration and activity of blood clotting factors, hyperfibrynogenemia and overeactivity ofplatelets. On the other hand, inhibition of normal fibrinolysis occurs in obese persons. The goal of this study was to examine disorders of coagulation and fibrinolysis developing in obese persons, taking also into account hormonal and metabolic changes, endothelium damage and the influence of adipocytokines on the hemostasis mechanisms. PMID- 17726875 TI - [85-years-old patient with paraneoplastic polyneuropathy]. AB - Symptoms associated with neoplasms that are not a direct result of tumor growth, metastases, concomitant infection or antineoplastic treatment are known as paraneoplastic syndrome (PS). PS results from autoimmune reaction against antigens common to host nervous cells and neoplasm. The most common neurological PS are Lambert-Eaton syndrome, paraneoplastic cerebellar degeneration and polyneuropathies. The most common neoplasms inducing PS are oat cell lung carcinoma, ovarian carcinoma, breast carcinoma, neuroblastoma, thymoma and lymphoma. From 2001 to 2004 at the Dept. of Neurology, Ageing, Degenerative and Cerebrovascular Diseases the paraneoplastic polyneuropathy was diagnosed in 6 patients. The authors report on a 86-year-old male with peripheral polyneuropathy and respiratory failure who presented PS ten months prior to finding of primary neoplastic lesion in lungs. The authors discuss diagnostic and therapeutic problems in patients with PS. This report reminds that in each unclear case of polyneuropathy PS should be strongly suspected. PMID- 17726876 TI - [Multiple primary malignancies of the genitourinary tract--renal cell carcinoma and seminoma testis]. AB - Multiple primary malignancies are tumors which present a definite picture of malignancy, each must be distinct and the possibility that one is a metastasis of another must be excluded. Authors present rare case of renal cancer associated with testicular cancer. PMID- 17726877 TI - [The influence of postgraduate studies in Berlin on the research activity of Wladyslaw Bieganski]. AB - The authors showed that Wladyslaw Bieganski's postgraduate studies in Berlin played a significant rule in his scientific activity. They also presented the impact of lectures of F.T. Frerichs, S. Henoch, F.K. Westphal and R. Virchow. His stay in Berlin was for Bieganski an advantage, giving him the opportunity to improve his medical knowledge, encouraged him to scientific works and made him aware of significance of problems connected with the theory of medical studies. PMID- 17726878 TI - [Patient's consent to treatment with reference to the development of medical ethics]. AB - In the paper the development of the patient's rights to informed consent to treatment has been discussed with reference to codes of medical ethics. The expression of the patient's rights and recognition of his/her active part in the course of treatment was proceeding gradually and parallel to the evolution of the subjective term "patient". Nowadays the patient's rights are determined by many declarations and international conventions, e.g. the Human Rights and Dignity Convention (1996). The so-called informed consent includes the right to the complete information about the course of treatment as well as the risk taken especially during surgical treatment and the right of a shared decision to choose the treatment. Patients who are unconscious and those with limited consciousness constitute the problem that is still being solved. It is expected that along with the development of medical ethics, the medico-legal regulations concerning the above mentioned issues will be specified soon. Besides the obligatory legal regulations, in many difficult cases the assessment and decision whether the patient's consent is informed or not, burden only a physician's conscience. PMID- 17726879 TI - [Can the placebo be the cure?]. AB - Effect of placebo still brings out questionable views and opinions, despite achievements of modern medicine. Placebo has been a component of healing process since the beginning of our history. Given consciously or unconsciously is responsible for the success of medicine before randomized clinical trials. This article reviews the short history of placebos and gives series of examples of the effects and advocates a more rigorous approach to their understanding. The role and meaning of placebos in the clinical trials have been presented since its power has been discovered in the 1955. But we still know little about placebos. For that reason there is a necessity to study the effect of placebo with the same rigor that has been applied to other treatment. According to some authors, this effect particularly concerns psychological and neurological diseases with signs of restlessness, pain and depression. In these cases, effect of placebos may often exemplify as well as distort the evaluation of treatment and efficacy of the drug. Those being engaged in clinical trials must recognize and manage the reality of placebos rather than the attempt to eliminate or disparage them. PMID- 17726880 TI - [Not Available]. PMID- 17726881 TI - [Not Available]. PMID- 17726882 TI - [Not Available]. PMID- 17726883 TI - [Not Available]. PMID- 17726884 TI - [Not Available]. PMID- 17726885 TI - [Not Available]. PMID- 17726886 TI - [Not Available]. PMID- 17726887 TI - [Not Available]. PMID- 17726888 TI - [Not Available]. PMID- 17726889 TI - [Not Available]. PMID- 17726890 TI - [Not Available]. PMID- 17726892 TI - [Not Available]. PMID- 17726891 TI - [Not Available]. PMID- 17726893 TI - [Not Available]. PMID- 17726894 TI - [Not Available]. PMID- 17726895 TI - [Not Available]. PMID- 17726896 TI - [Not Available]. PMID- 17726897 TI - [Not Available]. PMID- 17726898 TI - [Between science and beliefs]. PMID- 17726899 TI - [Controlled drinking for alcohol-dependent patients]. AB - Controlled drinking should be included in the treatment of alcohol-dependent patients. Research has showed that treatment plans which allow controlled drinking as a possible outcome yield better results in the long run than those in which abstinence is imposed. Controlled drinking can be a goal in itself, a step towards abstinence or a way of limiting alcohol-related problems. Accepting that the patient set his own treatment goals helps reinforce therapeutic rapport and diminish drop-out. Furthermore, the treatment approach becomes more finely shaded, as it helps patients not to waver continuously between abstinence and massive drinking. PMID- 17726900 TI - [Medical stakes and prospects in alcohol use amongst the elderly]. AB - Alcohol use disorders (including excessive drinking and dependence) are a common health problem in the elderly. Identification remains difficult. Standardized questionnaires do not adapt adequately in the old person's context. Specific geriatric troubles will become apparent and should alert the care-giver: falls, fractures, global state alteration, decompensated co-morbidities, multiple drug interactions, loss in daily-life activities, neuro psychological alterations. Alcohol must be integrated in each differential diagnosis procedure. An efficient management is possible including a multidisciplinary team: general practitioner, geriatrics and alcohol specialists, and the home working health network. Specialized care (for withdrawal and relapse prevention) and general care (education and re-socialisation) increase the outcome. PMID- 17726901 TI - [Talking about alcohol in general practice]. AB - Talking about alcohol in general practice Talking about alcohol drinking remains a real challenge for the internist. The high level of morbidity and mortality related to alcohol consumption is presently well-known but it is still difficult for the internist of talking alcohol with his patients. Because of a lack of medical education or often afraid of patients reactions, the internist could be driven to avoid the topic. And rarely the patient wants to talk about it by his own. Some tools are useful and are key for opening the conversation. Skinner pyramid, standard drinks, "J" curve, AUDIT or FACE questionnaires are easily available. They give to the practitioner opportunities to talk about alcohol before the situation has become really serious and discouraging. PMID- 17726902 TI - [From adolescence to alcohol and vice versa]. AB - Dependency and inner freedom hinge one upon the other. Adolescence is a turning point in life where the link between childhood and the discovery of new freedoms is forged. Partaking of alcohol is random and the tipping point towards alcohol abuse is dependent on many factors, some of which are psychic. When these factors are dominant and they tip the balance too heavily, psychoanalytic psychotherapy becomes a useful tool to avoid slipping into addiction. PMID- 17726903 TI - [Implementation of a coordinated action plan of indications and follow-up for alcohol dependent patients in the state of Vaud]. AB - Alcohol dependence is a chronic disease with many consequences and needs long term follow-up. The Public Health Service of the state of Vaud has decided to create a coordinated action plan of indications and follow-up for alcohol dependent patients covering the whole state. As described in this article, the aims of this action plan are to standardize the evaluation, the care and the follow-up for alcohol dependent patients, to improve the accessibility to care by promoting less intense care and to improve the continuity of care from inpatient treatment to ambulatory care. This action plan aims to allow a better accessibility to specialized care, to improve treatment adherence and a reduction of relapses. PMID- 17726904 TI - [A brief motivational intervention targeting multi-risk behaviours among young people]. AB - Teenagers and young adults often combine alcohol, tobacco, cannabis or other drugs use and related hazardous behaviours. This article presents a brief motivational intervention (BMI) targeting multiple substance use and related behaviours. The values and projects that can enter into conflict with the substance use are discussed in order to introduce a change perspective. Talking and thinking freely about change in a non-judgmental, empathic and collaborative manner can lead to an effective behaviour change. This time-limited BMI is appropriate and promising in a primary care. PMID- 17726905 TI - [Intracardiac echocardiography: a new tool for interventional cardiology]. AB - Intracardiac echocardiography is a new technique based on the use of ultrasonic diagnostic catheter, which can be introduced through the femoral vein up of the right atrium. Intracardiac echocardiography provides bidimensional views, coupled to colour and pulsed Doppler. This review summarizes multiple applications of intracardiac echocardiography in the field of interventional cardiology, particularly during percutaneous closure of patent foramen ovale or atrial septal defect. A major advantage of intracardiac echocardiography is the possibility of avoiding general anaesthesia as well as providing equivalent information to the reference technique of transoesophageal echocardiography. PMID- 17726906 TI - [Sessile serrated adenoma: an underdiagnosed colonic polyp]. AB - Serrated polyps of the colon represent a large morphological spectrum of lesions. They comprise the hyperplastic polyp considered as an innocuous lesion for many years, the traditional serrated adenoma presenting a potential of cancerisation and the recently described the sessile serrated adenoma which seems to be a potential precursor of colonic cancer with microsatellite instability and which probably uses an alternate polyp-neoplasia pathway in addition to the classical adenoma-carcinoma sequence. The aims of this article intend to inform of new concept of colonic carcinogenesis, to be aware of a serrated colonic polyp entity recently described and to use a same nomenclature to facilitate the dialogue between pathologists and clinicians. PMID- 17726907 TI - [Innocence and guilt of cholesterol (2)]. PMID- 17726908 TI - [Journalism in a story within a story]. PMID- 17726909 TI - [The dark backstage of the Metagenex case (I)]. PMID- 17726910 TI - [What is left of the clinical examination?]. PMID- 17726911 TI - Psychiatric manifestations of neurologic disease: where are we headed? AB - Neuropsychiatry represents a field of medicine situated at the crossroads of neurology and psychiatry, and deals with the interface of behavioral phenomena driven by brain dysfunction. Psychiatric symptoms are highly prevalent in these conditions, are a major source of disability and diminished quality of life, and potentially represent the target of treatment interventions that stand to significantly decrease the suffering they generate. In this article, the disease paradigm is explained, with particular attention to its role as an organizing principle for the field. Specific diseases including traumatic brain injury, stroke, Parkinson's disease, Alzheimer's disease, multiple sclerosis, and epilepsy are explored in relation to the presentation of multiple psychiatric phenotypes in each, associations with underlying brain pathology, and existing treatment approaches. Finally the article explores the inherent complexities in this area of research and proposes a framework for future work based on the understanding of phenomenology and associated risk factors, the involvement of the rapidly advancing field of neuroscience, and targeted treatment development to serve as a road map for advancement in the field.. PMID- 17726913 TI - Frontal-subcortical circuitry and behavior. AB - The neuropsychiatric manifestations of neurodegenerative diseases are closely linked to neurocircuitry defects. Frontal-subcortical circuits, in particular, are effector mechanisms that allow the organism to act on its environment. In this paper, we present the three main frontal-subcortical circuits: the dorsolateral prefrontal circuit allows the organization of information to facilitate a response; the anterior cingulate circuit is required for motivated behavior; and the orbitofrontal circuit allows the integration of limbic and emotional information into behavioral responses. Impaired executive functions, apathy, and impulsivity are hallmarks of frontal-subcortical circuit dysfunction. A variety of other neuropsychiatric disorders, such as Tourette's syndrome, Huntington's disease, obsessive-compulsive disorder, attention deficit/hyperactivity disorder, schizophrenia, and mood disorders may result from disturbances that have a direct or indirect impact on the integrity or functioning of these loops. PMID- 17726912 TI - Neuropsychiatric manifestations of depression in multiple sclerosis: neuroinflammatory, neuroendocrine, and neurotrophic mechanisms in the pathogenesis of immune-mediated depression. AB - Evidence suggests that depression in multiple sclerosis (MS) is largely biologically mediated by some of the same processes involved in the immunopathogenesis of this neurologic disease. In particular, the increase in proinflammatory cytokines, activation of the hypothalamic-pituitary-adrenal (HPA) axis, and reduction in neurotrophic factors that occur in MS may each account for the increased rate of depression seen in MS. The possible contributions of these neuroinflammatory, neuroendocrine, and neurotrophic mechanisms suggest a diverse array of novel treatment strategies for depression, both in the context of inflammatory conditions as well as in idiopathic depression. Furthermore, if such processes in MS play a causative role in the pathogenesis of depression, and depression in turn has affects on neurophysiological processes related to immune function, then treatment of depression might have a positive effect on MS disease progression. This makes treating MS depression a neuropsychiatric imperative. PMID- 17726914 TI - Frontotemporal dementia to Alzheimer's disease. AB - Behavioral manifestations may dominate the clinical picture of the frontal variant of frontotemporal dementia (fv-FTD) for a long time before the appearance of true cognitive deficits. On the other hand, a deficit in the episodic memory domain represents the main manifestation of Alzheimer's disease (AD). Many behavioral disorders have been described in the clinical course of both FTD and AD; however, apathy and personality changes characterize frontal dementias, while depression dominates in AD, at least in the earlier stages. Depending on the distribution of neural damage, different patterns of noncognitive manifestations may be expected in different subtypes of FTD. Recent research on the social cognition deficit in FTD has offered new insights into the relationship between cognition and behavior, suggesting that some aspects of the behavioral changes in dementia may be generated by impairment in this domain. PMID- 17726917 TI - Neuropsychiatry of Huntington's disease. AB - Psychiatric manifestations are an integral part of Huntington's disease. They may be divided into those syndromes which resemble idiopathic disorders, but for which HD patients may be particularly at risk, those constellations which are peculiar to HD and related conditions, such as the executive dysfunction syndrome, and those symptoms that can truly be regarded as nonspecific, such as delirium. Most of these problems are believed to arise from subcortical neuropathologic changes. Major depression is a common psychiatric diagnosis, but the executive dysfunction syndrome, a difficult-to-define condition characterized by often simultaneous apathy and disinhibition, may be even more widespread. There are no large controlled studies of psychiatric treatments in HD, but case series, anecdotal reports, and clinical experience indicate that many of these syndromes respond readily to treatment. Further study of the neuropsychiatry of HD may help to reveal the underpinnings of psychiatric conditions found in the general population. PMID- 17726916 TI - Visual hallucinatory syndromes: past, present, and future. AB - In 1936, two clinical reviews, one by de Morsier, the other by L'Hermitte and de Ajuriaguerra, formulated an approach to visual hallucinations that continues to this day. Breaking with previous traditions, the papers championed visual hallucinations as worthy of study in their own right, de-emphasizing the clinical significance of their visual contents and distancing them from visual illusions. De Morsier described a set of visual hallucinatory syndromes based on the wider neurological and psychiatric context, many of which remain relevant today; however, one-the Charles Bonnet Syndrome-sparked 70 years of controversy over the role of the eye. Here, the history of visual hallucinatory syndromes and the eye dispute is reviewed, together with advances in perceptual neuroscience that question core assumptions of our current approach. From a neurobiological perspective, three syndromes emerge that relate to specific dysfunctions of afferent, cholinergic and serotonergic visual circuitry and promise future therapeutic advances. PMID- 17726915 TI - Tourette's syndrome: clinical features, pathophysiology, and therapeutic approaches. AB - Tourette's syndrome (TS) is a disorder characterized by simple and complex motor tics, vocal tics, and frequently obsessive-compulsive symptoms. Its onset occurs before the age of 21. Typically, TS shows a waxing and waning course, but a chronification of the tics, even during later life, is often observed. TS mainly occurs in boys, and shows genetic heritability with differing penetrance. The pathological mechanism is still unclear Neuroanatomical and neuroimaging studies, as well as effective treatment using antipsychotics, suggest that a disturbance of the dopaminergic system in the basal ganglia plays an important role in the pathogenesis of TS. Several possibly causative mechanisms of the disturbed dopaminergic neurotransmission are discussed, with the main emphasis on the infection-triggered-inflammatory immune process. Extrapyramidal movement disorders are known to occur as a symptom of poststreptococcal disease, such as in Sydenham's chorea. Cases of childhood TS are proposed to be caused by such a poststreptococcal mechanism, being part of a spectrum of childhood neurobehavioral disorders termed pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS). The overlap between TS and PANDAS is discussed, and a critical view of the PANDAS concept is presented. The therapeutic implications of the different pathological mechanisms are described, taking into consideration not only the acute or chronic natures of different infections, but also an autoimmune process. Moreover, therapeutic strategies using typical and atypical antipsychotics, and also experimental therapies such as repetitive transcranial magnetic stimulation and deep brain stimulation, are critically discussed. PMID- 17726920 TI - [Discharge management in neonatology]. PMID- 17726919 TI - Quality of life in schizophrenic patients. AB - In the last decades, there has been increased interest in the field of quality of life in mental disorders in general, and particularly in schizophrenia. In addition, the appearance of the atypical antipsychotic drugs (amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone) with different therapeutic and side-effect profiles, has promoted a greater interest in assessing the quality of life of schizophrenic patients. In this paper we will briefly summarize the difficulties in assessing quality of life in schizophrenic patients, as well as the results concerning their quality of life and the influence of psychopathology, especially negative and depressive symptoms, on it. We will also review data from recent clinical trials showing the impact ofantipsychotic treatments and their side effects upon quality of life. PMID- 17726918 TI - Neuropsychiatric manifestations in CADASIL. AB - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small-artery disease of mid adulthood caused by mutations of the NOTCH3 gene. The disease is responsible for widespread white-matter lesions associated with lacunar infarctions in various subcortical areas. The disease is responsible for migraine with aura and ischemic strokes, and is associated with various degrees of cognitive impairment and with mood disturbances. CADASIL is considered as a unique model to investigate what is known as "subcortical ischemic vascular dementia." Recent data suggest that the number of lacunar infarctions and severity of cerebral atrophy are the main magnetic resonance imaging markers associated with cognitive and motor disabilities in this disorder. Mood disturbances are reported in 10% to 20% of patients, most often in association with cognitive alterations. Their exact origin remains unknown; the presence of ischemic lesions within the basal ganglia or the frontal white matter may promote the occurrence of these symptoms. Further studies are needed to better understand the relationships between cerebral lesions and both cognitive and psychiatric symptoms in this small-vessel disease of the brain. PMID- 17726921 TI - [Treatment with botulinum toxin in neurologic pediatrics]. PMID- 17726922 TI - [Quality improvement by introduction of primary nursing in the ambulatory pediatric nursing]. PMID- 17726923 TI - [Cramped like in a sardine box]. PMID- 17726924 TI - [Lice, fleas and other beasts]. AB - Bedbugs, lice, fleas and mites are blood-sucking ectoparasites whose bites cause allergic skin reactions. Diagnosis of bites is based on the morphology of the skin eruptions and the pattern of involved skin areas. Confirmation of the diagnosis often requires detection of the causal parasite. The main reservoir for ectoparasites (e.g., bedbugs, fleas, lice and scabies mites) are humans, but animals are also known to harbor ectoparasites (e.g., certain fleas and mites). Fleas, body lice and certain mite larvae in the tropics can transmit infectious diseases, but bedbugs, headlice, pubic lice and scabies mites cannot. Therapy is primarily directed against itching and bacterial superinfections. Pediculosis and scabies are additionally treated with t0pical insecticides. In order to kill freshly hatched larvae, topical treatmentmust be repeated after one week. In the case of pediculosis, people who have come into contact with symptomatic individuals also need to be treated, whereas with scabies, all contact persons must undergo treatment in order toprevent further transmission. Topicalinsecticides, in combination with anti-itch treatment, is usually sufficientto immediately relieve the symptoms and promote permanent healing of the skin lesions. PMID- 17726925 TI - [Palliative care: taking into consideration special needs of children!]. PMID- 17726926 TI - [Rings are risk factors of bacterial colonization of hands!]. PMID- 17726927 TI - [Leipzig Nursing Fair: more hygiene against MRSA]. PMID- 17726928 TI - [BeKD e.V. strikes the balance: there is no equal treatment for the nursing occupations!]. PMID- 17726929 TI - [Causes of overweight and obesity are sufficiently known]. PMID- 17726930 TI - [Telephone hotline for FSME vaccination]. PMID- 17726931 TI - [Many faces--one disease: fibromyalgia]. PMID- 17726932 TI - Clinical snapshot. Ocular swelling in a pug. PMID- 17726933 TI - Hyperadrenocorticism: treating dogs. AB - This article is a complete review of all reported therapies for hyperadrenocorticism in dogs. Both medical and surgical options for treating pituitary-dependent hyperadrenocorticism and adrenal tumor-related disease are discussed, and the efficacy, safety, and use of these treatments are compared. PMID- 17726934 TI - Clinical snapshot. A positive FIV antibody test result in a kitten. PMID- 17726935 TI - Hypernatremia in dogs. AB - Hypernatremia is potentially life threatening and is caused by imbalances in water and sodium that occur from either water loss or sodium gain, often in the presence of inadequate water intake. The resultant hyperosmolarity, if acute or severe, can result in rapid shifts of water from the intracellular to extracellular space, causing intracranial hemorrhage and neurologic changes. Correction of hypernatremia through inappropriate fluid therapy can result in even more severe complications, ranging from cerebral edema to coma and death. This article reviews the pathophysiology, causes, classification, treatment, and prognosis of hypernatremia. PMID- 17726936 TI - White coat syndrome: prevention and treatment. PMID- 17726937 TI - Rattlesnake envenomation. AB - Snake envenomation has been widely reported throughout the human and veterinary literature. The effects of venom include coagulation disorders, neurotoxicity, and tissue effects, such as local swelling and necrosis. Significant progress has been made in understanding the pathophysiology of envenomation, leading to changes in treatment protocols. Recent developments include the production of a new antivenin and a canine rattlesnake vaccine. PMID- 17726938 TI - Clinical snapshot. Head shaking and ear scratching in a cat. PMID- 17726939 TI - Clinical snapshot. Abnormality in a rabbit. PMID- 17726940 TI - [Radiological and medical consequences of the Chemobyl atomic power station accident in the Russian Federation]. PMID- 17726941 TI - [A simulation model of the influence of hygienic factors of the environment on mortality]. AB - The paper describes a simulation model of the chronic influence of environmental factors on mortality. The relationship of the risk of death from environment related causes with to influence of environmental factors is shown to be near linear. A model is proposed to assess the environment by the mortality rates. PMID- 17726942 TI - [Prevalence of malignancies in the climatic and natural zones of Kalmykia]. AB - The purpose of this investigation was to study cancer morbidity in Kalmykia due to the global scale of desertification and impact of industrial and agricultural discharges from the adjoining regions on the carcinogenic situation; to examine the trace composition of soil; to determine the levels of heavy metals from iron to lead, that affect the prevalence of malignancies in the environmental areas of the Republic. In the analyzed period, under the influence of desertification, carcinogenic factors, and life style, the incidence of male and female malignancies increased by 44 and 28%, respectively. PMID- 17726943 TI - [Psychophysiological reactions in young men in the Magadan Region]. AB - The paper considers the specific features of psychophysiological reactions in 11 form male pupils living in different areas of the Far North-Eastern Russia. As natural and climatic conditions intensify, the response to an imposed photic stimulus increases. The young men from the settlement of Evensk may be assumed to have a more prolonged maturation of the central nervous system and organism as a whole. PMID- 17726944 TI - [The hair levels of heavy metals in children living 27 in the North of the Tyumen Region]. PMID- 17726945 TI - [Effect of containers material on the structure of water in its storage]. AB - When water is stored, the material of crockery is of vital importance as it affects the properties of water. Contacting the material having a crystalline structure causes water structurization and uncrystalline materials (plastic and enamel ware) fail to maintain the structural property of water or destruct the property in storage. Ceramic foodware positively affects the structure of water although there is a significant increase in the content of its structurized fraction only in just 2 days. The water storage type that is optimal and most acceptable in private life is glassware in diffused sunlight that causes positive water structural changes increasing by day 2. Addition of a metallic component, silver in particular, enhances the process of water structurization. The worst type is plastic ware water storage. PMID- 17726946 TI - [Stability of bituminous-salt mass-washing sarin, soman, and Russian VX destruction products in the aquatic environment and their effects of the sanitary conditions of water supplies]. AB - The water environmental stability of O-isopropylmethyl phosphonate, O pinacolylmethyl phosphonate, and O-isobutylmethyl phosphonate was studied. The very high hydrolytic stability of these products was established. The threshold and non-effective concentrations of O-isopropylmethyl phosphonate, O pinacolylmethyl phosphonate, and O-isobutylmethyl phosphonate were determined, which affected the sanitary conditions of water bodies. PMID- 17726948 TI - [Comprehensive study of lighting at a higher educational purpose]. AB - The visual fatigue-affecting conditions of the classes of a higher educational institute were examined in students. The authors determined the light level of working places and its compliance with hygienic regulations of the factors influencing the students' visual perception. They analyzed and identified avoidable causes of variance of the light level and conjugate variables. Guidelines for optimizing the light level have been developed, by taking into account the lowest required tangible cost. A program of organizational actions, which aimed at following the sanitary-and-hygienic specifications at higher school, has been worked out. PMID- 17726949 TI - [Trends in morbidity with temporary disability as an occupational risk index]. PMID- 17726947 TI - [Hygienic assessment of the factors of a work flow in filling station operators]. PMID- 17726950 TI - [Prevention of stress states in full-time students]. AB - The study was undertaken to use the biologically active additive (BAA) Kalifen as a component of the jellies BIO-LAD for students' adaptation to academic load. Two groups of male volunteers aged 20-22 years were examined. Group 1 (control) included 20 healthy male donors of the comparable age. Group 2 comprised 10 students who were asked to take 100 mg of the jellies containing the BAA Kalifen (TU 9128-152-02067936-2006), which was equivalent to 100 mg of total polyphenols a day, on fasting every day after biochemical blood studies. The serum tested before the experiment showed hypertriglyceridemia and hypercholesterolemia, suppressed hepatic etherifying function and imbalance of the fractional content of phospholipids. Exhaustion of the antioxidative system, increased lipid peroxidation, and impaired erythrocytic membrane permeability were also ascertained. Supplementation of the jellies normalized the biochemical parameters under study. From the above discussion, it follows that the jellies BIO-LAD should be used as a purposefully acting product to prevent mental and emotional stress. PMID- 17726951 TI - [Hygienic problems of specialized training at high school]. AB - Different variants of teaching organization at high school have been studied on the basis of a comparative analysis. The 10th-form pupils of specialized classes have been established to have a lower level of mental performance than those of the same age from general educational classes. This is associated with the drastic increase in a weekly summary educational load as compared with that in a ninth form, which was characteristic of the pupils of specialized classes; their educational load is increased by 8.5 hours whereas that is by 2.5 hours in those of educational classes. The adaptation of the pupils of specialized classes to new specialized educational conditions is completed by the 11th form, as suggested by the positive changes in their mental performance. The study of different models of specialized education organization has revealed that a multispecialized model that can individualize an academic process to a greater extent is hygienically most favorable. Recommendations have been developed for the hygienic optimization of an academic process at high school. PMID- 17726952 TI - [The prevalence and pattern of locomotor disorders in senior pupils]. AB - The study deals with the analysis of the prevalence of disorders of the locomotor apparatus (LMA) in senior schoolchildren from 9th-to-11th-forms of various general educational establishments, such as a secondary general educational school, a technical lyceum (general educational and specialized classes), and a physical engineering school. The academic load, educational conditions, and teaching methods in each establishment differed and conformed to the implemented school-based educational program. Sixty hundred and eighteen senior schoolchildren were examined. In the senior pupils of the physical engineering school the educational program of which is characterized by increased academic loads, the prevalence of scoliotic deformity of the spine was found to be 3-5 times greater than that in those of the secondary general educational school. The higher prevalence of LMA disorders in the pupils from the general educational classes of the technical lyceum (8.6- and 3-fold in boys and girls, respectively) is indicative of the leading influence of a social factor on the development of scoliotic deformity. The impact of increased academic loads on the MDA is also suggested by the difference in the incidence of MDA disorders among the pupils of general educational and specialized classes of the technical lyceum. Emphasis is laid on the need for taking into account the findings to substantiate comprehensive preventive programs and health-improving measures in the educational establishments. PMID- 17726953 TI - [The individual development of children from an industrial town]. AB - Congenital morphogenetic variants (CMGV) and anthropometric indices as markers of individual development were analyzed in 4-7-year-old children, visiting the kindergarten, in 2 Magnitogorsk districts with varying chemical ambient air pollution. The basic characteristics of CMGV were found to be stable in relation to gender. The study indicated that the average number of CMGV, rare CMGV (at a rate of not greater than 1%) and individual CMGV depended on the degree of chemical ambient air pollution. It was larger in a more polluted area. Lower anthropometric indices (height and body weight) were observed in boys living in a more polluted area. PMID- 17726954 TI - [Main trends in the physical development of young children]. AB - The physical development ofjunior schoolchildren living in Ufa, a large industrial town, was studied. The findings were compared with the data of the 1946-1947, 1972, and 1998 studies of physical development. Analysis of the materials indicated that the accelerating processes among young children continued till the end of the previous century, the maximum change in anthropometric indices being observed in the period of 1947 to 1972. In the past years, there has been a gradual decrease in the average values of length in junior schoolchildren and there has been a tendency for body weight and chest circumference to decrease. PMID- 17726955 TI - [Biomonitoring of formaldehyde in the urinary samples from the pediatric population in the Irkutsk Region]. AB - Formaldehyde is one of the major pollutants of both ambient and indoors air. Thus, by comparing the concentrations of formaldehyde in ambient air (on study days) and in the air of classes and living rooms, the study has demonstrated that they may be 13.5 and 10.5 times greater than the normal values in the classes and living rooms, respectively. Biomonitoring of formaldehyde in the urinary samples from the pediatric population of the Irkutsk Region as an indicator of its chemical action has revealed the higher average group concentration of the substance in the urinary samples from urban children than that in rural ones (235 children from 6 inhabited localities). A significant correlation has been also found between the levels of formaldehyde in the urine of children (aged 5-10 years) and its concentration in the air of living rooms in the town of Shelekhov. PMID- 17726956 TI - [Change in salivary nitric oxide levels in students in the examinational period]. AB - The influence of examination-induced psychoemotional stress on hemodynamic parameters and salivary nitric oxide (NO) levels was studied in students. Before examinations, the examinees with a sympathotonic response (75.0%) were observed to have diminished salivary NO excretion that was retained within 24-hours after an exam. There was a significant negative correlation between the amount of NO and the values of blood pressure. The examinees with a parasympathetic response (25%) were found to have elevated salivary NO levels with lowered blood pressures in the pre- and postexaminational periods. PMID- 17726957 TI - [Problems in the regional sociohygienic monitoring of the population's health]. PMID- 17726958 TI - [The ways of improvement of the Armed Forces medical service organizational structure according to the character of modern military conflicts]. AB - During the period of reformation and decrease in the number of Russian Federation Armed Forces as well as the medical service the use of existing infrastructure of military district medical service and formation of Stationery Hospital Base (SHB) is an alternative to organization of treatment-and-evacuation measures in the armed conflicts and local wars. Taking into account the peculiarities and schemes of organization of treatment-and-evacuation measures in military conflicts and according to the calculated needs for medical service forces and means necessary for forces group medical support the SHB organizational structure can be consisted of three main modules. 1. The Headquarters Module is an operative group of medical service of military district rear headquarters. 2. The Stationery Module consists a number of medical institutions of military district medical service. 3. The Mobile Module consists a number of medical units and institutions of military district medical service that are capable to dislocate and perform the special tasks when and where it is necessary. PMID- 17726959 TI - [The Personal professional potential of graduates from military medical higher schools and its use in completing the post-graduate course]. PMID- 17726960 TI - [The experience of using fucidin and fucicort in the treatment of servicemen with pyodermia]. PMID- 17726961 TI - [Surgical infection during the fighting injuries of locomotor system]. PMID- 17726962 TI - [The treatment of primary and recurrent of basaliomas of head and neck soft and bony tissues]. PMID- 17726963 TI - [The evaluation of effectiveness of conservative therapy for knee joint osteoarthrosis]. PMID- 17726964 TI - [An optimal algorithm for ambulatory therapy of anxious-and-phobic disorders]. PMID- 17726965 TI - [The modern aspects of vernal encephalitis problems: the epidemic process, diagnosis and prophylaxis]. PMID- 17726967 TI - [A veteran's word]. PMID- 17726966 TI - [The perspectives of using the modern technological equipment for preparation of injection solutions in the military drugstores]. AB - In modern conditions the most rational approach to medicinal support is an optimal combination of nomenclature of ready drugs and drugs prepared extemporary. Independently of the place where the drugs are prepared (industrial production or preparation under conditions of drugstores) they should correspond to the following requirements: to have therapeutic effectiveness, to be harmless for patient and injection solutions (IS) should be sterile, apyretic and with minimal microbial contamination before thermal sterilization. At present it can be achieved only with the wide use of semiautomatic or automatic equipment for IS preparation arranged into technological complexes. Such complexes are home produced. Besides The Main Military Medical Headquarters has created the complex, which can be used in stationary and field conditions. The use of technological complexes for IS preparation provides their adequate quality and contributes to budget economy at the expense of decreased purchases of IS produced in the factories. PMID- 17726968 TI - [The 1326th center of state sanitary-and-epidemiological inspection of Privolzhsko-Uralsky military district is 65 years]. PMID- 17726969 TI - [The military psychophysiology department of military medical academy is 10 years]. PMID- 17726971 TI - [The military medical journal of Republic of Belarus]. PMID- 17726972 TI - [Multidimensional estimation of mental health of the military men at mass psyhoprophylaxis inspections]. PMID- 17726973 TI - [Ways of optimization of air-medical evacuation of wounded and ill patients during the armed conflict]. AB - The article is devoted to the experience of airmedical evacuation struck during operations in territory of the Chechen Republic of 1999-2002. We consider, that optimal medical-evacuation system in local wars, local fight actions and battles consists only two stages, then victim after first physician aid is evacuated to specialized medical unit. Own experience of preflight preparation and support is generalized and analysed at carrying out of airmedical evacuation of 928 critically wounded patients and the struck on tactical, operative and strategic levels during a confrontation in territory of the Chechen Republic (1999-2002). PMID- 17726974 TI - [Substantiation of the medical specifications for dispensary maintenance of children of the military men by all kinds of the outpatient stomatologic help]. PMID- 17726976 TI - [Experience of preparation and over-dislocation of military hospital on the base of medical group of special destination (purpose) of the military area in the region of act of nature]. PMID- 17726975 TI - [First help at acute coronary syndrome]. PMID- 17726977 TI - [The modern approaches to the choice of infusion agents used in the treatment of severe injuries and burns]. AB - The article presents an analytical review of modern possibilities of the complex pathogenic treatment for severe traumas and injuries at the expense of systemic use of infusion drugs with antihypoxic and antioxidant effects. It is shown that hypoxia and oxidative stress is the typical; pathologic process that accompanies the development of traumatic disease during severe surgical pathology. One of the effective ways to correct the developing disorders is to use the regulatory or substrate antihypoxants as well as the drugs with antioxidant effect. PMID- 17726978 TI - [Rheumatic fever at the patients of middle-age]. PMID- 17726979 TI - [Diagnostics, treatment and preventive maintenance of tromb complications at onkostomatologic patients at chemistry-therapy and operative intervention]. PMID- 17726980 TI - [Sanatorium treatment of the military men with traumatic damages of the extremity]. PMID- 17726981 TI - [Special features of chronic cystitis with leukoplasional changes of a mucous environment women's urinary bladder]. PMID- 17726982 TI - [Special features of mental and somatic status of the employees of law enforcement bodies of the Chechen Republic]. AB - With the purpose of study of features of psychical and somatic prosperity of employees of organs of internal affairs of Chechen Republic the inspection of 64 employees was conducted. It is set that a posttraumatic stress disorder (PTSR) was exposed for 3% inspected employees-contracters. The separate symptoms of PTSR were observed for 2/5 contracters and at 1/4 workings on permanent basis. Complaints about somatic disfunctions were present at more than 1/2 employees, dischargings official duties by contract, and 2/5--workings on permanent basis. Presence of intercommunications of complaints with the subscales of questionnaire of traumatic stress, specifies on psychosomatic nature of violations of somatic health because of finding in extreme battle conditions. PMID- 17726984 TI - [Bases of the scientific concept of a military-medical museum]. PMID- 17726985 TI - [S.M. Luk'ianov--doctor, publicist and public figure]. PMID- 17726986 TI - Recent advances in the treatment of autoimmune mucocutaneous blistering diseases. PMID- 17726987 TI - Timing, positioning, and sequential staging in esthetic implant therapy: a four dimensional perspective. AB - Many articles address the predictability of immediate implant placement into extraction sockets; however, there are only a few reports that mention the indications and limitations of this technique. The aim of this article is to re examine specific indications for immediate implant placement and to clarify the timing or "fourth dimension" relative to extraction and implant placement. The expanded concept of four-dimensional implant treatment planning involves the new axis of time, which must be considered along with the traditional spatial or three-dimensional management of implant positioning. PMID- 17726988 TI - Orthodontic microsurgery: a new surgically guided technique for dental movement. AB - Eight patients with malocclusions were treated with a new orthodontic-surgical technique that reduces the duration of treatment compared to conventional techniques. The monocortical tooth dislocation and ligament distraction (MTDLD) technique combines two different dental movements that work separately but simultaneously on opposite root surfaces. On the root surface corresponding to the direction of movement, vertical and horizontal microsurgical corticotomies are performed around each tooth root with a piezosurgical microsaw to eliminate cortical bone resistance. The immediate application of strong biomechanical forces produces rapid dislocation of the root and the cortical bone together. On the root surface opposite the direction of movement, the force of dislocation produces rapid distraction of ligament fibers. During the osteogenic process that follows, application of normal orthodontic biomechanics achieves the final tooth movement. All eight patients underwent periodontal and radiologic examinations for more than 1 year after treatment. No periodontal defects were observed in any of the patients, including one with a severe malocclusion and a thin periodontal tissue biotype. Compared to traditional orthodontic therapy, the average treatment time with the MTDLD technique in the mandible and maxilla was reduced by 60% and 70%, respectively. PMID- 17726989 TI - Evaluation of root coverage with two connective tissue grafts obtained from the same location. AB - The purpose of this study was to compare the clinical root coverage achieved with two connective tissue grafts that were removed from the same donor area at different times and used in subepithelial grafts for root coverage. Sixty patients, each of whom had two connective tissue grafts removed from the same donor area at different times, were included in this study. The connective tissue grafts were used in two different subepithelial grafts for root coverage. The subepithelial grafts with both the first and second connective tissue grafts produced statistically significant changes in recession, probing depth, width of keratinized tissue, and attachment level. The changes obtained in the clinical measurements were not statistically significantly different between the first and second connective tissue grafts. The mean percentages of root coverage with the first and second connective tissue grafts were 95.4% and 98.2%, respectively, a statistically significant difference. None of the factors evaluated (sex, age, smoking history, and time between the two surgeries) could be related to statistically significant differences in the mean root coverage obtained. In this study, the second connective tissue graft produced greater mean root coverage than the first connective tissue graft. PMID- 17726990 TI - Histologic analysis of the acellular dermal matrix graft incorporation process: a pilot study in dogs. AB - Clinical results with acellular dermal matrix graft (ADMG) in periodontal surgeries suggest that the material is incorporated by the host tissues. However, histologic studies of the ADMG incorporation process are limited. The objective of this study was to evaluate the incorporation of ADMG into gingival tissues in a dog model. Gingival recession-type defects were created at the canines of six dogs. After 6 weeks, periodontal surgeries to repair the defects were performed using ADMG. Two animals each were sacrificed after 4, 8, and 12 weeks. At 4 weeks, thick collagen fibers from the ADMG were clearly seen in the connective tissue, and some blood vessels were penetrating into the ADMG. At 8 weeks, blood vessel penetration was enhanced, and collagen fiber bundles from the ADMG were seen sending branches into the connective tissue in all directions. After 12 weeks, the ADMG and the connective tissue seemed to be well integrated into a single highly vascularized structure, indicating almost complete incorporation of the ADMG. PMID- 17726991 TI - Beauty and the teeth: perception of tooth color and its influence on the overall judgment of facial attractiveness. AB - This study investigated the influence of changes in tooth color on judgments of facial attractiveness. Standardized photographs were presented, and teeth were digitally manipulated (main categories: original, whitened, colored; filler category: impaired). Participants were instructed to evaluate the faces for attractiveness. Additionally, they were asked to name facial features they found either positive or negative with regard to attractiveness. Whitened teeth were mentioned more often in a positive way but did not improve participants' assessment of attractiveness. A colored tooth did not attract attention, and the attractiveness judgment did not worsen. Tooth color is thus not necessarily perceived and does not have a major impact on facial attractiveness. PMID- 17726992 TI - A 1- to 12-year clinical evaluation of 106 endosseous implants supporting fixed and removable prostheses. AB - The purpose of this article is to report on the long-term clinical evaluation of patients treated with dental implants. A total of 106 implants were placed in 34 patients and restored with fixed partial dentures and overdentures. The 12-year cumulative implant survival and success rates were 95.2% and 90.2%, respectively. Probing depths around mandibular implants were significantly lower than those around maxillary implants (P < .05). The cumulative implant success rate in nonsmokers was 97.7%, but this dropped to 75.81% in smokers. Also, patients rehabilitated with implant-supported overdentures had more peri-implant tissue inflammation than patients with fixed prostheses. PMID- 17726993 TI - Immediate loading: a simple protocol to create a passively fitting provisional fixed implant-supported complete denture in 1 day. AB - Many studies have shown success with immediate loading of dental implants. The purpose of this paper is to report on a procedure that places implants with a sand-blasted and acid-etched surface and loads them with a fixed, provisional, immediately loaded mandibular complete denture, all in a single day. The various surgical, prosthetic, and laboratory phases are explained, with particular attention paid to a luting technique that is able to reduce prosthetic misfit. A series of 14 patients was treated with this protocol and followed for a mean of 28.2 months. A 100% implant survival rate was achieved, and all prostheses were in place and functioning at the most recent follow-up. PMID- 17726994 TI - Sling and tag suturing technique for coronally advanced flap. AB - The coronally advanced flap (CAF), either by itself or combined with other soft tissue grafts, provides predictable root coverage. However, it is a major challenge to suture and secure the flap coronally and stabilize its position over the entire healing period. Thus, the purpose of this study was to introduce a modified incision design and a suturing technique (sling and tag [SAT]) to enhance the results of CAF for root coverage. Ten patients with Miller Class I gingival recession defects (> or = 2.5 mm) were treated. Clinical parameters assessed included recession depth (RD), recession width (RW), clinical attachment level (CAL), probing depth (PD), gingival tissue thickness (GT), and keratinized gingiva width (KGW). Measurements were taken at baseline and 6 months and 1 year later. The paired t test was used to compare presurgical and postsurgical results. Statistically significant (P < .05) reductions in RD (2.6 +/- 0.5 mm) and RW (2.9 +/- 0.9 mm) were observed at 1 year. An average of 93.0% +/- 14.8% root coverage was achieved. In addition, a statistically significant CAL gain of 3.3 +/- 1.0 mm was obtained. No statistically significant differences were found in PD and KGW before and after therapy. The newly introduced flap design and SAT suturing technique may enhance the results of CAF for root coverage. PMID- 17726995 TI - Platelet-rich plasma and bone healing: a histologic study in titanium bone chambers. AB - The potential benefits of platelet-rich plasma in the healing of isolated defects are unclear. The purpose of this study was to evaluate the effects of PRP on bone healing in titanium bone chambers, which represented isolated defects. PRP was prepared from blood collected from six adult female albino New Zealand rabbits. Titanium bone chambers with a 4-mm inner diameter were implanted into the tibiae of each animal at baseline and 2 weeks later; chambers healed for 6 or 8 weeks, either with PRP (test) or without PRP (control). Bone chambers were harvested from each animal and processed for histologic evaluation. Bone formation in 8 week test samples was not significantly different from that of the 6-week test samples. In control samples, more bone formation was seen at 8 weeks than at 6 weeks. The fibrous tissue content in control samples was higher than that of the test group in superficial sections, revealing that the tissue differentiation rate was higher in the test chambers. Time-dependent bone tissue differentiation in bone chambers augmented with PRP is higher than in normal wound healing, and PRP seems to increase the rate of tissue differentiation in early healing. PMID- 17726996 TI - Diversity in nursing education: how well are we doing? PMID- 17726997 TI - Affirming At-Risk Minorities for Success (ARMS): retention, graduation, and success on the NCLEX-RN. AB - Increasing ethnic and racial diversity in the U.S. population combined with inadequate minority representation in the nursing profession requires innovative strategies to recruit, retain, and graduate nurses from diverse ethnic and racial populations. Affirming At-Risk Minorities for Success (ARMS) was funded by a U.S. Department of Health and Human Services Basic Nurse Education and Practice Program grant. Participants (N = 64) were enrolled in a baccalaureate degree nursing program that has been predominantly White/ Anglo and is located in the south-central region of the United States. Research objectives were to increase program retention, graduation rates, and success on the National Council Licensure Examination for Registered Nurses (NCLEX-RN) for minority or educationally disadvantaged students through programmatic interventions, including mentoring and advising, tutoring, and educational seminars. The comparison group was non-ARMS students derived from a comprehensive database (N = 265). Results indicated that interventions positively affected graduation rates (measure of retention = 98%), significantly affected grades in the Leadership Management capstone course, and eliminated the effects of ethnicity on NCLEX-RN success. PMID- 17726998 TI - Student perceptions: the influence of a Nursing Workforce Diversity Grant on retention. AB - This article reports the perceptions of Hispanic/Latino and American Indian students concerning the influence of a Nursing Workforce Diversity Grant (ALCANCE) on their educational experiences in a baccalaureate nursing program. The grant provided an educational pipeline for these students, supporting them financially, personally, and academically from middle school through graduation from the nursing program. Fifteen students receiving grant services during the upper-division nursing major completed a 76-item questionnaire assessing the influence of such services at the end of each of four semesters in the nursing program. Analysis of these questionnaires and examination of responses to open ended questions at the end of each instrument indicated a generally positive influence of ALCANCE on student experiences. However, there remains a need for the creation of additional caring educational environments and further research to better understand effective strategies for addressing recruitment and retention in American Indian and Hispanic/Latino nursing students. PMID- 17726999 TI - Cultural competence of baccalaureate nursing faculty. AB - This randomized, stratified, descriptive, cross-sectional survey design used Campinha-Bacote's Inventory for Assessing the Process of Cultural Competence Among Healthcare Professionals-Revised (IAPCC-R) to assess the cultural competence of a convenience sample of 170 randomly selected baccalaureate nursing (BSN) program faculty. The mailed survey also assessed factors that were helpful in increasing comfort levels in caring for individuals from other cultures and gathered self-report data on cultural content in faculty academic preparation and current employing programs. Results indicated BSN faculty were culturally competent. Faculty teaching in the states with the most immigrants were more culturally competent than were faculty teaching in the states with the least immigrants. Immersion or working in another culture were the most frequently cited methods of increasing cultural comfort. PMID- 17727000 TI - Improving cross-cultural communication in health professions education. AB - In the District of Columbia, health education programs are required for all students, yet inner-city elementary public charter schools do not have enough funding to hire nursing personnel in their schools to provide such programs to their students. Therefore, some public charter school administrators partner with community agencies to bring additional cost-free resources to their schools. However, collaborative and partnership activities in DC can be fraught with racial strife. This article describes the partnership between the Georgetown University School of Nursing & Health Studies, the School of Medicine, and select DC elementary schools and presents a specific example of one partnership between the University and an elementary public charter school. The article describes a communication breakdown between the predominately Caucasian nursing and medical students and the predominately African American faculty, staff, and students of the public charter school, with suggestions about how to avoid and overcome such conflicts in the future. PMID- 17727001 TI - Learning through teaching: empowering students and culturally diverse patients at a community-based nursing care center. AB - This article addresses the effect of a nursing care center on student learning. Associate degree nursing students spend clinical days at a nursing care center that was created in collaboration with an inner-city clinic serving individuals who are uninsured and underinsured. The nursing students learn cultural sensitivity, teaching strategies, and interdisciplinary skills. The service learning experience benefits the nursing students, the nursing department of the college, the patients who visit the nursing care center, the clinic, and the community. This article describes the development of the nursing care center, examples of teaching-learning opportunities, and evidence of student learning. This successful collaboration between a community college and an inner-city clinic can be Associareplicated by other nursing programs. PMID- 17727003 TI - Taking the sting out of examination review. AB - Since using this method, examination reviews have focused less on arguing for points and more on comprehending the material. Examination reviews are already stressful for students and faculty; posting the examination on the walls is a quick and easy way to facilitate a difficult task. PMID- 17727002 TI - Developing cultural competence in nursing students through their experiences with a refugee population. AB - Nursing students in an urban university in southwestern Pennsylvania began visiting newly relocated Somali refugees as part of their community health nursing (CHN) clinical course-work. The purpose of this qualitative study was to relate the students' experiences in their clinical visits with the refugees to the development of cultural competence. Findings identify the many challenges confronted by students and present strategies for resolution. The level of skills needed for the care of vulnerable populations should be considered when assigning undergraduate students to the clinical setting. PMID- 17727004 TI - The top ten ways physicians are devalued (more work, less pay). PMID- 17727005 TI - Health plan advocacy--the next generation. PMID- 17727006 TI - HIV and Iowa law: what health care providers need to know. PMID- 17727007 TI - Incident tracking: managing your risks. PMID- 17727008 TI - Global Health in the Heartland. PMID- 17727009 TI - Childhood obesity--are we making progress? PMID- 17727010 TI - Radiologic case study. Diagnosis. The case: Langerhans cell histiocytosis. PMID- 17727011 TI - Hip arthroscopy for developmental dislocation. PMID- 17727012 TI - Universal health care and the single-payer system. PMID- 17727013 TI - Distal hybrid interlocking in the femoral shaft fracture. AB - This technique may be beneficial for stabilizing fractures less invasively and may decrease complications, such as nonunion and postoperative infection, by avoiding iatrogenic devascularization of the fracture site. PMID- 17727014 TI - Treatment of massive tibial bone loss due to chronic draining osteomyelitis: fibula transport using the Ilizarov frame. AB - This article affirms the value of the application of the Ilizarov frame for gradual transport of the ipsilateral fibula to replace massive tibial bone loss following chronic refractory osteomyelitis. PMID- 17727015 TI - Immobilization for scaphoid fracture: forearm rotation in long arm thumb-spica versus Munster thumb-spica casts. AB - A Munster thumb-spica cast may play a role in the conservative treatment of non displaced scaphoid fractures by allowing some elbow motion during the long immobilization period. PMID- 17727016 TI - Lactose: the hidden culprit in medication intolerance? AB - Although reports are rare, lactose-containing medications may cause patient discomfort and subsequently affect medication adherence. PMID- 17727017 TI - Treatment of complex proximal femoral fractures with the proximal femur locking compression plate. AB - The PF-LCP represents a feasible alternative for the treatment of unstable inter- and subtrochanteric fractures. PMID- 17727018 TI - Nutraceuticals in the management of osteoarthritis. PMID- 17727019 TI - Ultrasonic cement removal in revision arthroplasty. AB - Efficient and safe cement removal is critical in revision arthroplasty. Conventional manual cement removal by hand or power-driven instruments can be time-consuming, require osteotomy, and be associated with complications such as cortical perforation, fracture, or bone loss. Ultrasonic devices offer an alternative method of cement removal by converting mechanical vibrations into thermal energy, liquefying the cement. This facilitates selective cement removal, preserves bone, decreases cortical perforation risk, and eliminates the need for osteotomy. However, potential for thermal injury exists. Ultrasound basic science, mechanism of action, and clinical applications with specific emphasis on methods to limit excessive heat generation are reviewed. PMID- 17727020 TI - Determination of radiographic guidelines for percutaneous fixation of proximal humerus fractures using a cadaveric model. AB - The humeral heads of whole body cadaveric shoulders underwent fluoroscopic evaluation with the head divided into three zones on both anteroposterior (AP) and axillary views creating nine zones. Five AP and three axillary fluoroscopic images in different rotational positions were assessed for pin penetration. All images were evaluated for pin penetration and the AP view was evaluated for lesser tuberosity location. Pins placed appropriately below the subchondral bone did not appear to penetrate the joint on any fluoroscopic image. Pins placed 2 mm beyond the articular surface were appropriately viewed exiting the head on most views (64%) but falsely appeared within the head on several others (36%). Pins perforating the posterior head were problematic for accurate detection on AP views (missed in 87%), but this was avoided by externally rotating the humerus to 60 degrees. Articular penetration cannot always be appreciated radiographically and special efforts are necessary to avoid this problem including the use of various rotational views as well as the use of appropriate landmarks for orientation such as the lesser tuberosity position. PMID- 17727021 TI - Sacral and lumbar-pelvic morphology in high-grade spondylolisthesis. AB - Numerous authors have stressed the importance of posterior arch, vertebral bodies, and intervertebral disk dysplastic changes in lumbosacral spondylolisthesis. An extensive morphologic analysis was conducted of the lumbosacral junction in a series of 100 consecutive patients presenting with severe lumbosacral spondylolisthesis. Statistical correlations were found between the pelvic incidence, sacral slope, and pelvic tilt, as found in healthy volunteers. A statistical relationship exists between the lumbosacral kyphosis and pelvic parameters that explains the global sagittal "balance" of this pathological posture. A well-defined morphological criterion, the "S1 index," strongly correlated with the severity and stiffness of lumbosacral spondylolisthesis. PMID- 17727022 TI - Porcine small intestine submucosa for repair of goat meniscal defects. AB - This study evaluated the effectiveness of small intestine submucosa used as a graft to fill surgically created meniscal defects in a large animal model. Four goats underwent unilateral interior subtotal meniscectomies (approximately 70%) within the avascular portion of the medial meniscus. The contralateral meniscus acted as a control. Grafts of porcine small intestine submucosa were trimmed to fill the resected defects and sutured into place. After surgery the operated knees were casted in partial flexion to limit weight bearing on the affected limb. All of the animals were sacrificed at 12 weeks at which point meniscal regeneration and articular cartilage degradation were evaluated by gross and histologic examination. Grossly, the defects in the small intestine submucosa grafted goats were partially filled with meniscal-appearing connective tissue. Histologically, the replacement tissue was typified by the presence of dense, cellular, irregularly organized connective tissue. Evaluation of the articular cartilage displayed increased degeneration in the grafted compartment of the operative knees. Each of the operative menisci partially regenerated. The grafts were conducive to repopulation with host meniscal elements. Despite partial meniscal regeneration, comparatively more articular cartilage degeneration in the treated knees was observed than in the untreated contralateral controls. PMID- 17727023 TI - Release of the subscapularis tendon and muscle: a limited gain in length. AB - This study measured in vitro the degree of lateral advancement of the subscapularis tendon achieved by circumferential release. Thirty-eight cadaveric shoulders underwent circumferential subscapularis release with anterior capsulotomy. Release was performed in two phases. The first phase consisted of four stages: 1) cutting the capsule parallel to the superior border of the subscapularis tendon to the level of the glenoid; 2) division of the anterior capsule and blunt dissection along the glenoid neck; 3) safe separation of the capsule and muscle inferiorly; and 4) blunt, with a finger, dissection between the conjoined tendon and the subscapularis to the level of the joint line. The second phase was performed by cutting the coracohumeral ligament and the consistently found fibrous band that connects the superior aspect of the subscapularis tendon to the base of the coracoid. After each phase, 3 kg of traction were applied to the muscle and the lateral advancement of the subscapularis was measured using a millimeter caliper. The lateral advancement of the subscapularis was 5.5 +/- 3.4 mm after the first step and 9.8 +/- 4.5 mm after the second step. The difference was statistically significant (P < .001). These results indicate that, although necessary, anterior soft tissue balancing during shoulder replacement is limited. PMID- 17727024 TI - Clinical course of open metatarsal fractures. AB - Little information exists regarding open fractures of the foot and no studies have reported open metatarsal fractures. Limited local soft tissue coverage makes this a distinct type of injury. Ten patients with open metatarsal fractures were treated. Six sustained Gustilo Grade I or II injuries; all healed without the need for additional soft tissue coverage. Four patients with Gustilo IIIB developed complications and all went on to eventually require amputation. This data indicates less severe open metatarsal fractures heal without complications, but more severe injuries require amputation. PMID- 17727025 TI - Crescent fracture of the pelvis in a 4-year-old child. PMID- 17727026 TI - Intramuscular hematoma following a midvastus approach during primary total knee arthroplasty. PMID- 17727027 TI - Osteoid osteoma with cartilage formation of the distal phalanx in the toe. PMID- 17727028 TI - [Animal and human Cryptosporidiosis in rural zone in Vietnam (Cu Chi district, Ho Chi-Minh-City)]. AB - A pilot study was carried out in May-June 2003 to evaluate the epidemiological situation of cryptosporidiosis in the Cu Chi district, a rural zone of Ho-Chi Minh City Vietnam. The modified acid-fast stain of the stools revealed that 10/202 (5%) cows, 1/29 (3.5%) cattle breeders, and 2/53 (3.8%) under five year- old children with diarrhoea were infected by this germ. Unconfined cattle had a significantly higher risk of infection than penned animals (odds ratio [OR]: 8.3; 95% confidence interval [CI]: 1.06-64.7; p: 0.025). PMID- 17727029 TI - [Presentation of cerebral toxocariasis with mental confusion in an adult: case report and review of the literature]. AB - Toxocariasis is usually responsible for visceral larva migrans syndroms. Nervous system involvement is a rare complication. In this report, we describe one case of meningoencephalitis due to Toxocara canis in a 73-year-old man presenting with mental confusion. The diagnosis of cerebral toxocariasis was confirmed by immunodiagnosis in both serum and cerebro-spinal fluid. Cerebral toxocariasis may be suspected in patients presenting with some neurological patterns including: confusion, meningitis, meningo-encephalitis, meningo-myelitis, when the etiological assessment remains negative and the environmental context is favourable. Finding evidence of specific antibodies in both cerebro spinal fluid and serum is mandatory for the diagnosis. The main clinical features concerning cerebral toxocariasis, diagnostic tools, and therapeutic measures are discussed. PMID- 17727030 TI - [Darier and Ferrand dermatofibrosarcoma. About 7 cases at the Ouagadougou teaching hospital, Burkina Faso]. AB - The authors report 7 cases of dermatofibrosarcoma of Darier and Ferrand over a 7 year- period at the Yalgado-Ouedraogo teaching hospital, that is to say an average of 1 case per year. A male predominance was noted (4 males and 3 females), average age: 48; 5 recurrences out of 7, with an average delay of 3 years for recurrence, preferentially localised on the trunk (5 cases) and thigh (2 cases). They emphasize the importance of wide surgical exeresis and histopathology essential to confirm the diagnosis. Finally they point out the importance of clinical surveillance because of frequent recurrences. PMID- 17727031 TI - [Endemic treponematoses in Maputo, Mozambique]. AB - Endemic treponematoses are present in inter-tropical countries in Africa, America, Indonesia and Papua New Guinea. Epidemiology and transmission of the disease are well known. After eradication in some countries after mass treatment in 1950-60, a resurgence of endemic treponematoses has been reported since 1980 90. We present 2 cases of endemic syphilis from the dermatology unit of the Maputo hospital, the first to be described in Mozambique. The endemic syphilis was probably facilitated by the social conditions induced by the Mozambican civil war between 1975 and 1993. PMID- 17727032 TI - [First case of Stevens-Johnson syndrome in a patient treated by Triomune in Abidjan, Cote d'lvoire]. AB - The authors report the first case of Stevens-Johnson syndrome which has occurred in a 45 year old patient treated by Triomune containing nevirapine. Triomune is used within the context of the African antiretroviral initiative access. It was a mild form whose evolution was favourable when nevirapine was stopped. The prevalence of this affection should increase with the larger use of nevirapine in our countries and the attention of both prescriber and patient must be requested. PMID- 17727033 TI - [Treatment of ocular lesions due to Elapidae venom spitting in Central African Republic: epidemiological and clinical aspects]. AB - This survey concerns 16 patients admitted to Bangui teaching national hospital center, coming from Ngakobo health center 450 km from the South East of Bangui, between September 2001 and May 2002. All of them have undergone a basic ophthalmological examination 16 patients have been hospitalised in the service of ophthalmology among them, 11 didn't go to the consultation. All the 16 patients were males, 18 to 46 years old. Five of them had bilateral corneal lesions and eleven patients presented unilateral lesions. Two patients had a corneal perforation at admission. The initial visual acuity of the concerned eye was estimated between LP(-) and 3/10th. The visual acuity valued after exit was LP(-) to 6/10. Four patients out of sixteen (two eyes with bilateral lesions and two with unilateral lesion) (six eyes) received as initial treatment, water rinse on the spot of the accident, then a local treatment by antibiotics administrated in the dispensary of the Ngakobo Province. Eight patients (two bilateral and six unilateral lesions) received a traditional treatment while five of them received it before their transfer to Bangui and 3 patients just before their arrival in Bangui. Four patients (five eyes) had no treatment at all. The nature of this traditional treatment, often of mineral and vegetal origin has not been specified. The main after-effects are corneal opacities, varying according to size, localization and gravity. At the beginning, 9 cases out 16 are generally diffused and superficial keratitis. After some days of treatment, 8 cases developed into corneal opacity freeing thus the visual axis. 3 cases of keratitis developed into a purulent melting then to a corneal perforation. Elapidae's spits on the eye are frequent in sugar cane cultivation areas. They can provoke some severe erosive corneal lesions, in absence of adequate and early management. The administration of traditional treatment most often complicates the clinical issue. Nursing staff, medical personnel and family should pay attention to the ocular toxicity of these septic matters and to the first cares provided to the patient before his early transfer to hospital. PMID- 17727034 TI - [Molecular surveillance of sulfadoxine-pyrimethamine-resistant Plasmodium falciparum in Sao Tome and Principe]. AB - The prevalence of point mutations associated with resistance to sulfadoxine and pyrimethamine was determined by sequencing the fragments of genes encoding dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr), respectively in 59 isolates collected during 2002-2003 in Sao Tome and Principe to develop an early warning system of drug-resistant P. falciparum. Almost all isolates (57 of 59, 97%) were dhfr mutant. The majority of the isolates (43 of 59, 73%; 16 with mixed alleles) carried the triple dhfr mutations (lle-51/Arg-59/Asn-108). The presence of dhps mutations were only limited to positions 436 and 437. The pure mutant codon Gly-437 was present in 39 out of 59 isolates (66%), in association with Ser-436 (n=34) or Ala-436 (n=5). Mixed isolates displayed different combinations of 436 (Ser, Ala ou Phe) and 437 (Gly with or without Ala) alleles. None of the isolates carried mutant 540, 581 or 613 codons. A total of 39 isolates (66%) were characterized as quadruple mutants (i.e. triple dhfr mutations + Gly-437 dhps mutant allele). Monitoring the possible emergence of isolates carrying multiple dhfr and dhps mutations, in particular codon Glu-540, may be used as an early warning system which indicates a decrease in sulfadoxine pyrimethamine efficacy. PMID- 17727035 TI - [Identification of high risks regions of schistosomiasis in Cote d'lvoire]. AB - Regional and national epidemiological data being not available for coherent and efficient control strategies, the identification of high risk zones of schistosomiasis was set up in 5 regions of Cote d'lvoire in April 1999. The inquiry was conducted by questionnaire in 1291 primary schools including 119624 pupils. After less than 2 months, the results revealed blood in urines and in stools in respectively 22035 (18.6%) and 27555 (23.3%) pupils. Out of 1089 (99.8%) schools at risk of schistosomae, 358 (32.9%) are high risk schools. They are to be found especially in the Agneby (30.8%) and the Marahoue (19.9%) regions identified as high risk areas where actions of control are then important to implement. They are followed by the Lakes regions (15%), the Middle-Comoe (12.6%) and Southern-Comoe (8.9%). These results should help to develop the schistosomiasis control in Cote d'lvoire. PMID- 17727036 TI - [Agricultural activities and malaria transmission in two eco-epidemiological settings in central Cote d'Ivoire]. AB - We comparatively studied the dynamics of malaria transmission in the villages of Zatta (located in close proximity to an irrigated rice perimeter) and Tiemelekro (rural area with traditional agriculture), central Cote d'Ivoire. In the former village, the irrigated rice farming had been interrupted in 2003/2004 due to a farmers' conflict over land. In each village, mosquitoes were collected by human landing catches at night in sentinel houses. Anopheles gambiae was the predominant malaria vector, followed by An. funestus. In Zatta, the return to an irrigated rice farming in January 2005 was paralleled by a significant increase of the entomological inoculation rate (EIR) ranging from 38 infective bites per person per year (ib/ply) in 2003 to 295 ib/ply in 2005. In Tiemelekro high EIRs were found in 2003 (342 ib/ply) and 2005 (572 ib/ply). Our findings confirm that changes in irrigated rice agriculture influence malaria transmission dynamics, and call for control measures that are readily adapted to local eco epidemiological settings. PMID- 17727037 TI - [Prevalence of HBs antigen in blood donors in the Bouake regional centre of blood transfusion in 2001]. AB - A prospective cross-sectional study was conducted in the regional center of blood transfusion in Bouake from December 1, 2001 to February 28, 2002. One thousand two hundred thirty one new blood donors were tested. HBs Antigen detection was made according to ELISA technique (Hepanostika HBs Ag Uni-Form II). HBs Antigen prevalence in blood donors in Bouake was 12.5%. One hundred fifty four blood donors were tested positive and were divided into 131 males (85%) and 23 females (15%). Their average age was 27, 5 years old (18-65 years). HBs Antigen carriage rate was lower in females and students. They were mainly pupils (62%) and had risk factors of hepatitis B infection (intramuscular injection, multiple sexual partners, unsafe sex). HBs Antigen carriage rate in blood donors is high in Bouake and justifies the systematic screening of this Antigen in any blood donor to reduce the transfusion risk. On the other hand, it is necessary to modify the blood collection strategy in order to make the most of the donation and to decrease the residual risk. PMID- 17727038 TI - [Yaws in Cote d'lvoire: health problem forgotten and neglected]. AB - Yaws is endemic in Cote d'Ivoire, with an hospital incidence estimated by the medical statistics at 0.58 per thousand in 2000; cases of yaws were notified in all medical districts. This study describes the yaws situation in Cote d'Ivoire based on available hospital statistics and a cross section investigation. The yaws diagnoses during the investigation were based on clinic lesions. The yaws prevalence found at the end of the investigation was 5 per thousand: the majority of the patients were children under 15 years old (82%) and male (91%). Only 27% of diagnosed patients had a medical treatment at the time of the study. Yaws is still endemic in Cote d'Ivoire which underlines the need for an implementation of a national control strategy. PMID- 17727039 TI - [Laboratory based human leptospirosis surveillance in New Caledonia (2001-2005)]. AB - The Pasteur Institute in New Caledonia performs for this territory the biological diagnosis of human leptospirosis; therefore its activity locally gives a rather exhaustive description of this pathology. The results presented here cover the 2001-2005 period and describe the principal epidemiological and biological features of human leptospirosis in New Caledonia. The investigated patients were recruited by the main medical structures: territorial and provincial hospitals, public dispensaries, clinics and general practitioners. The laboratory used the microagglutination test for serological investigations and PCR methods for the early detection of Leptospira genome in clinical samples. 239 cases of leptospirosis were biologically confirmed among 6690 tested patients, giving an average incidence of 21 cases per 100000/year, and a lethality rate of 5.4%. The sex-ratio was 1.8 male/female, patients were predominantly belonging to the 20-50 year age group and were inhabitants from the Northern Province. The circulating serogroups were mainly Icterohaemorrhagiae (69%), Australis (8%) and Pyrogenes (6%). The annual incidence peak occurred in April at the end of the warm season, and the importance of annual outbreaks could be linked with El Nino, the main regional climatic phenomenon. PMID- 17727040 TI - [Assessing epidemiological consequences two years after the tsunami of 26 December 2004?]. AB - In December 2004, a very devastating tsunami struck the coasts of a number of countries along the Indian Ocean inducing about 280,000 deaths and at least 125,000 injured persons. As after such disaster the occurrence of large epidemics of cholera, malaria or arbovirus infections are to be expected. In fact, two years later, no outbreak has been reported among the exposed populations and this is probably the usual outcome for such disasters. However an real increase in number of cases of melioidosis and many bacterial or fungic infections affecting the pulmonary tract, the skin and the injured soft tissues, was noted mainly in repatriated tourists. These latter infections were due to rare or atypical, frequently multiresistant, microorganisms. PMID- 17727041 TI - [Pitched battle in Gueme between the Massa of Cameroon and Massa of Chad]. AB - To avenge an act of adultery a pitched battle broke out between the Massa from Cameroon and the Massa from Chad, ending with 82 wounded people on the Cameroonian side, mainly skull, face and upper limbs injuries. Considering the importance of cattle in the social relations in the Massa society particularly in matrimonial exchanges, the battles are often triggered by robbery of cows or bay an act of adultery. Massa are familiar with this type of battle where two long lines of men armed with stones and sticks, confront each other encouraged by the lines of the women. Their accessories (club, battle helmet), their compliance with the rules of the battle (to collect the injured, not to strike a man on the ground or who is injured, end of the fighting at dusk), explain the great number of wounded people, the epidemiology, and the type of injuries. Injured people are usually in care of traditional healers performing distinct techniques using local resources. The role of the women in this type of fighting illustrates their place in the Massa society. PMID- 17727042 TI - [Edmond Sergent's discoveries on the vectorial transmission of agents of human and animal infectious diseases]. AB - Edmond SERGENT has been head of the Institut Pasteur in Algeria from 1910 to 1963. During these years, he carried out an impressive scientific production and studied a lot of agents responsible for human, animal and plant diseases. In the field of vectorial transmission of infectious diseases, he made two essential discoveries: the transmission of cosmopolitan relapsing fever by human body louse in 1908, a year before Charles NICOLLE discovered the transmission of the classical exanthematic typhus by the same insect, and the transmission of cutaneous leishmaniasis by the phlebotomine sandfly. Moreover he made other discoveries in similar fields, such as the transmission of dromedary trypanosomiasis by Tabanids and later by stomoxys calcitrans, or the transmission of the pigeon Haemoproteus by Lynchia maura. Finally he described the transmission of Theileria dispar (now T. annulata) by the tick Hyalomma mauritanicum (1928). PMID- 17727043 TI - The declawing debate. PMID- 17727044 TI - A cat with a paw wound that was unresponsive to antibiotics. PMID- 17727045 TI - Hematemesis in a beagle. PMID- 17727046 TI - Canine pericardial effusion: pathophysiology and cause. AB - Pericardial effusion is the abnormal accumulation of fluid in the pericardial space. As the fluid volume and intrapericardial pressure increase, cardiac tamponade can develop. The most common causes of pericardial effusion include cardiac hemangiosarcoma, idiopathic pericardial effusion, and chemodectoma. Understanding the underlying cause is important in providing treatment recommendations and an accurate prognosis. PMID- 17727047 TI - Canine pericardial effusion: diagnosis,treatment, and prognosis. AB - Most cases of pericardial effusion can be diagnosed with a thorough physical examination. Physical examination findings may include muffled heart sounds, pulsus paradoxus, and jugular venous distention. Radiographs may show a globoid cardiac silhouette. Echocardiography is reliable in diagnosing pericardial effusion. Pericardiocentesis is indicated for the emergency treatment of pericardial tamponade. Pericardiectomy may improve survival in some dogs. The prognosis varies greatly, depending on the underlying cause. PMID- 17727048 TI - Dominance versus leadership in dog training. PMID- 17727049 TI - Canine infectious tracheobronchitis. PMID- 17727050 TI - Magnesium disturbances in critically ill patients. AB - Magnesium alterations can have a noticeable effect on the neuromuscular cardiovascular, and metabolic systems. With recent advances in point-of-care testing, it is now easier to monitor for changes in the serum magnesium concentration and implement therapies in the critical care setting. This article reviews the normal homeostatic mechanisms, clinical abnormalities, and therapeutic strategies for magnesium disturbances in critically ill patients. PMID- 17727051 TI - [Optimization of submerged culture condition for production of mycelial biomass by Armillaria mellea]. AB - OBJECTIVE: To optimize the submerged culture conditions for the production of mycelial biomass by Amillaria mellea. METHODS: Using the statistically based experimental design in a shake flask culture, optimum concentration of each medium component was determined using the statistical method. RESULTS: Dextrin was the suitable carbon source, bean cake extract was the suitable nitrogen source. Both corn steep liquor and thiamin favored the mycelial growth. Ethanol also favored the mycelial growth. (NH4 )2SO4 and NaNO3 inhibited mycelial growth whereas KH2PO4 favored the mycelial growth. CONCLUSION: The optimal combination of the media concentrations for mycelial growth was as follows: bean cake extract 25%, corn steep liquor 2%, dextrin 2.5%, thiamin 0.06%, ethanol 1.0%, KH2PO4 0.3%, pH 6.0. Under the optimal culture condition, the production of mycelial biomass achieved 1.9g/100ml. PMID- 17727052 TI - [Quality comparison between two cultivated Chinese yam-Kunming yam and Tiegun yam]. AB - OBJECTIVE: To compare the quality of cultivated Chinese yam (Dioscorea polystachya Turcz.) from Yunnan (Kunming yam) and Henan (Tiegum yam) by determining the content of dry substance in fresh sample and the contents of water extracts, ethanol extracts, starch, protein, crude-fat and polysaccharide in dry sample. METHOD: The above-mentioned indexes were determined by methods of air desiccation, cold-immersing, hot-immersing, iodine-blue coloration, half Micro-Kjeldahl, Soxhlet extraction and spectrophotometric method respectively. RESULT: In fresh sample, the content of dry substance of Kunming yam is a little lower than Tiegun yam; in dry sample, all indexes of Kunming yam are higher than or approach to those of Tiegun yam except the content of crude-fat. Especially the content of polysaccharide in Kunming yam is 64% higher than that of Tiegun yam. CONCLUSION: Kunming yam, with high quality, high yield and good taste, deserves paying close attention as a good variety. PMID- 17727053 TI - [Occurrence and control of Loxostege stieticatis on host plant Haloxylon ammodendron to Cistanche deserticola]. AB - The investigation of the occurrence and pesticide experiments of Loxostege stieticatis on Haloxylon ammodendron showed that Loxostege stieticatis is an explosive pest; it can be controlled with lower toxic pesticides such as deltametrin; the innocuous comprehension measure should be a good choice to control in field. PMID- 17727054 TI - [Research on the quality changes in pre- and post-processed pieces of Eucommia ulmoides]. AB - OBJECTIVE: To study the quality changes in pre- and post-processed pieces of Eucommia ulmoides Oliv. METHODS: The changes of the content of pinoresinol diglucoside, extract and fingerprint were studied. RESULTS: Pinoresinol diglucoside contents in post-processed pieces were lower than those in pre processed and alcohol extract had different changes because of its different habitats. Eucommia ulmoides consists of 11 common peaks, the one processed by salt-water consists of 8 Peaks. CONCLUSION: Processing can reduce the content of pinoresinol diglucoside. Alcohol extract has different changes. Eucommia ulmoides common peaks of its fingerprint reduce and mostly components descend after processed by salt-water. PMID- 17727055 TI - [Study on pharmacognosy of Ginkgo leaf]. AB - The primary study of Ginkgo leaf such as crude drug macroscopic and powder characteristics were carried out, and the flavonoids content in the leaf of Ginkgo in different areas of Gansu province was determined by HPLC, in order to provide scientific references for the exploitation of Ginkgo in Gansu province. PMID- 17727056 TI - [Stduy on flavonoids in Ligustrum lucidum]. AB - OBJECTIVE: To study chemical constituents of fruits of Ligustrum lucidum. METHOD: The chemical components were isolated and purified by silica gel and sephadex LH 20 column chromatogram. The chemical structures were elucidated on the basis of physic-chemical properities and spectral data. RESULT: Seven flavonoids were isolated and identified as apigenin(I), cosmosiin(II), apigenin-7-O-acetyl-beta-D glucoside(III), apigenin-7-O-beta-D-lutinoside (IV), luteolin (V), luteolin-7-O beta-D-glucopyranoside (VI), quercetin(II). CONCLUSION: Compounds II, IV, V were obtained from the fruits of the plant for the first time. PMID- 17727057 TI - [Study on antioxidant activity of two major secoiridoid glucosides in the fruits of Ligustrum lucidum Ait]. AB - The antioxidant effects of two major secoiridoid glucosides (nuezhenoside and G13, separated in our laboratory) from Fructus Ligustri Lucidi had already been assayed though DPPH radicals, respectively. The results revealed that these ingredients showed significant antioxidant activities. A positive correlation existed between total content and antioxidant activity. G13 had shown higher antioxidant activity than nuezhenoside. It implied that the structure of secoiridoid glucoside was postitive to antioxidant activity. Otherwise, the results could promote the deep research of Furctus Ligustri Lucidi on antioxidant mechanism. PMID- 17727058 TI - [Chemical constituents from Pyrethrum tatsienense]. AB - OBJECTIVE: To isolate and identify the chemical constituents from the whole plant of Pyrethrum tatsienense, which has been used as traditonal herb medicine in the treatment of some diseases. METHODS: The compounds were isolated by column chromatography and their structures were elucidated through spectroscopic analysis (NMR). RESULTS: Six compounds were isolated and identified as: linoeic acid, pinoresinol, (+)-pinoresinol-4'-O-beta-D- glucopyranoside, betulabuside A, dihydrosyringin. CONCLUSION: All these compounds were obtained from Pyrethrum tatsienense for the first time. PMID- 17727059 TI - [Studies on chemical constituents of Sambucus adnata]. AB - OBJECTIVE: To study the chemical constituents of Sambucus adnata. METHOD: Compounds were isolated by silica gel chromatography. Their structures were elucidated by means of spectral analysis. RESULT: Five compounds were isolated and identified as: 1-(3-hydroxy4-methoxyphenyl)-1',2'-ethanediol (1), ursolic acid (2 ), 1-( 3,4,5 -trimethoxyphenyl) -1', 2'-ethanediol (3), lariciresinol (4), 5, 7, 3', 4'-tetramethoxyflavone-3-O-rhamnopyranosyl-(1 --> 6) glucopyranoside(5). CONCLUSION: Compounds 1, 3, 4 and 5 were obtained from this plant for the first time. PMID- 17727060 TI - [GC-MS analysis of volatile constituents from five different kinds of Chinese eaglewood]. AB - Volatile oils of five different kinds of Chinese eaglewood were extracted with aether at room temperature. The chemical constituents and relative contents of the volatile oils were analysed by GC-MS. It showed that all the five volatile oils were mainly composed of sesquiterpenes, aromatic constituents and fatty acids. Several sesquiterpenes, such as hinesol, nootkatone, valerenic acid, velleral, guaiol, gamma-gurjunene, gamma-selinene, viridiflorol, isoaromadendrene epoxide, valencene, alpha-costol et. al., together with several aromatic constituents, 2,4-di-tert-butylphenol,4-methyl-2,6-di-tert-butylphenol, phenylpropionic acid, 1-(benzyloxy)-8-naphthol, anisylacetone, et. al. were found in the volatile oils of Chinese eaglewood for the first time. The samilarities and differences of the volatile oils from the five kinds of Chinese eaglewood were compared. It suggested that the quality of Chinese eaglewood could be evaluated by GC-MS analyse of the volatile oil. PMID- 17727061 TI - [Chemical constituents from aerial parts of Plumbago zeylanica Linn]. AB - OBJECTIVE: To investigate the chemical constituents of the aerial parts of Plumbago zeylanica Linn. METHODS: The constituents of the EtOAc-soluble portion in the 95% ethanol extract were isolated and purified by means of chromatography. Compounds were identified by their physical characteristics and spectral features. RESULTS: Nine compounds were isolated as plumbagin (I), isoshinanolone (II), plumbagic acid (III), beta-sitosterol (IV), 4-hydroxybenzaldehyde (V), trans-cinnamic acid (VI), vanillic acid (VII), 2, 5-dimethyl-7-hydroxychromone (VIII), indole-3-carboxaldehyde (IX). CONCLUSION: Compounds V, VII, VIII and IX were isolated for the first time from Plumbago Linn. PMID- 17727062 TI - [Quantitative analysis of galangin from propolis in different areas by HPLC]. AB - OBJECTIVE: To establish an HPLC method for determination of galangin in propolis. METHODS: HPLC method was established. Diamonsil C18 column was used, CH3OH-4% H3PO4 solution (65:35) as mobile phase, at the flow rate of 1.0 ml/min and the UV detection wavelength at 256 nm. RESULTS: The linear of galangin was 0.00412 - 0.02472 mg/ml (r2 = 0. 9998). The content of galangin was the highest in the propolis from Shandong (11.7 mg/g). The content of galangin was higher in the propolis from Neimeng and Henan, respectively 10. 5 mg/g,10. 3 mg/g, the content of galangin was the lowest in the propolis from Gansu (9.8 mg/g). CONCLUSION: HPLC method is simple and reliable for determination of galangin in propolis. PMID- 17727063 TI - [Study of inhibitory effect of extracts from Actinidia arguta on human carcinoma of esophagus cells]. AB - OBJECTIVE: To study the inhibitory effect of extracts from Actinidia arguta by n butyl alcohol on human carcinoma of esophagus cells (Eca-109) and Its mechanism. METHODS: MTT colonmetric assay was used to examine the growth inhibitory of concentration-effect (1 microg/ml, 10 microg/ml,100 microg/ml) and time-effect (24 h, 48 h, 72 h) of extracts from Actinidia arguta by n-butyl alcohol on Eca 109 cells. TUNEL test were performed to observe the apoptosis induced by the extracts (1 microg/ml, 10 microg/ml, 100 microg/ml) on Eca-109 cells. RESULTS: The inhibitory effect of the extracts on Eca-109 cells increased in a dose-time Manner and the highest rate of inhibition was 87.2%. The extracts could significantly induce apoptosis of Eca-109 cells, but in control group, apoptosis wasn't observed. CONCLUSION: The extracts from Actinidia arguta by n-butyl alcohol have good inhibitory effect on Eca-109 cells. PMID- 17727064 TI - [Immune-pharmacology study on the immunoregulatory effects of Dabuyin Wan in autoimmune mice induced by Campylobacter jejuni]. AB - OBJECTIVE: To study the immunoregulatory effect of Dabuyin Wan (DBYW) on cytokines of IFN-gamma and IL-4 and proliferation of T, B lymphocytes in autoimmune mice induced by Campylobacter jejuni. METHODS: Healthy female ICR mice were divided into 8 groups at random: normal control group (N), model group (M), model control group (MC), five different time administration groups (30 min, 1h, 1.5h, 2h, 3h). The mice were induced by Campylobacter jejuni with Complete Freund's Adjuvant as autoimmune animal model except N group. From the fifteenth day after primary immunization, the administration groups were given DBYW through gastric route in a dosage of 0.4 g/ml. At the same time, MC group were given physiological saline instead. All the administration lasted for 10 days. Blood samples were taken 30 min, 1h, 1.5h, 2h and 3h respectively after the last administration to detect the proliferation of T, B lymphocytes and to cultivate T lymphocytes which were taken from M group. The concentrations of gamma-interferon (IFN-gamma) and interleukin-4 (IL-4) in culture supernantants were measured by an enzyme-linked immunosorbent asay (ELISA) after 48h. The drug efficacy was evaluated by marking the curve of time-effect relationship in the chart. RESULTS: It was found that the concentrations of IFN-gamma was significantly lower in cultures with the drug-containing serum taken at 1-1.5 h after the treatment than that in cultures with the MC control serum (P < 0.01). Only the serum taken at 1.5h was found to enhance the production of IL-4 (P < 0.05). The proliferation of T, B lymphocytes was markedly inhibited by the drug-containing serum taken at 1 1.5 h after the treatment (P < 0.01). CONCLUSION: The drug-containing serum in mice taken at 1-1.5 h after ingestion of DBYW can regulate the immunologic function of autoimmune mice induced by Campylobacter jejuni. PMID- 17727065 TI - [Comparison of the effect of eight kinds of volatile oil of Chinese material medica on percutaneous absorption of ibuprofen in vitro]. AB - OBJECTIVE: To compare the permeation-enhancing effect of the volatile oil of eight kinds of Chinese material medica including Fructus Evodia, Radix Saposhnikoviae, Rhizoma Atractylodes lancea Radix Aucklandiae, Radix Curcuma wenyujin, Rhizoma et Radix Notopterygii, Lignum Aquilariae Resinatum, Herba Schizonepetae on the model drug of ibuprofen in order to provide theoretic foundation for the selection and application of natural penetration enhancer. METHODS: The permeation flux of ibuprofen was determined using the penetration experiment apparatus in vitro. The content of ibuprofen was measured by HPLC. RESULTS: All the above mentioned volatile oil showed permeation enhancing effect on ibuprofen in different degrees, and the enhancive permeation multiple was 3.46, 3.00, 2. 36, 2.32, 2.28, 2.01, 1.37 and 1.29. CONCLUSION: All eight kinds of volatile oil can enhance the percutaneous absorption of ibuprofen in vitro, among which the volatile oil of Fructus Evodia and Radix Saposhnikoviae showed significant penetration enhancing effect. PMID- 17727066 TI - [Study on lipid-regulating function for the extracts and their prescriptions from Semen Cassiae and fructus crataegi]. AB - OBJECTIVE: To study the effect of lipid-regulating function for extracts and their prescriptions from Semen Cassiae and Crataegus pinnatifida Bge. var. major N. E. Br. on serum lipid of hyperlipidema mice. METHODS: 1 week after being administered with extract of Semen Cassiae, extract of Crataegus pinatifida Bge. var. major N. E. Br. and different proportion mixture of them (180 mg/ kg), mice were treated with ip 75% fresh yelkfluid. The contents of TC, TG, HDL-C, LDL-C, apo AI and apo B were observed after 24 h. RESULTS: The levels of TC, TG, LDL-C and apoB in therapeutic group were lower than those in hyperlipidemic model group (P < 0.05, P < 0.01), especially in different proportion mixture groups. CONCLUSION: Lipid-regulating active part of Semen Cassiae and Crataegus pinatifida Bge. var. major N. E. Br. might inhibit hyperlipidemic formation, and mixture groups were more effective than those of its single extract. PMID- 17727067 TI - [Monomers optimization and properties evaluation of quercetin-imprinted polymer and its application to thin layer chromatography stationary phase]. AB - The quercetin-molecularly imprinted polymers with specific affinity and selectivity were prepared by using methacrylic acid (MAA), acrylamide (AM), N,N (diethylamino) ethyl methacrylate and 2-vinylpyridine as functional monomers, respectively. The adsorption properties for template were studied by equilibrium binding experiments. The results showed 2-VP and DEAEM based on ionic interaction with quercetin possessed better imprinting effects. Using the quercetin-imprinted polymers as thin layer chromatographic stationary could successfully separate the template from the other structurally related compounds. In addition, the influence on adsorption effect about the particle size and repeating times of MIP were investigated. PMID- 17727068 TI - [Studies on the extraction of active polysaccharide from Dendrobium huoshanense with Box-Behnken method]. AB - OBJECTIVE: In order to obtain preferable extraction rate of polysaccharide from Dendrobium huoshanense, best extraction conditions and decoloration method were investigated. METHODS: Five influential factors including extraction temperature, extraction time, ratio of material to water, repetition times and extraction pH were carried out. Extraction model of polysaccharide from Dendrobium huoshanense was established by Box-Behnken method. RESULTS: In the conditions of 69.4 degrees C of the temperature, 1.57h of the extraction time, 1: 20 of the ratio of material to water, two of the repetition times and 5.9 of the pH, the extraction rate reached the peak of 0.1821 g/g. Taking into account of decoloration, 65.47% of decoloration rate was obtained with DEAE-52 method. CONCLUSION: Extraction model of polysaccharide from Dendrobium huoshanense established by Box-Behnken method can precisely predict the experiment results. In the best conditions deduced from the model, the extraction rate of polysccharide is high and so is the decoloration rate. PMID- 17727069 TI - [Studies on extraction process optimization of patrinia scabra Bunge saponins]. AB - OBJECTIVE: To optimize the conditions for the extraction of Patrinia scabra Bunge saponins. METHODS: Orthogonal experimental design and ultrasonic method were employed to examine the conditions for the extraction by determination of saponins. RESULTS: The optimun condition for the extraction of Patrinia scabra Bunge saponins was as follows: 65% ethanol for 40 minutes, 55 degrees C and 210 watt of ultrasonic efficinecy. CONCLUSION: The extraction method of Patrinia scabra Bunge sponins is simple and efficient. PMID- 17727070 TI - [Optimizing the best extraction condition of semi-bionic extraction for licorice by unifrom design]. AB - OBJECTIVE: To optimize the best extraction condition of semi-bionic extraction for licorice. METHODS: The best extraction condition of the semi-bionic extraction for licorice by uniform design was optimized with glycyrrhizic acid, total flavonoids, total polysaccharides, total HPLC integrate area and dried extract weight as the indexes. RESULTS: The optimized technologic condition: The pH values of the water for the 1st, 2nd, and 3rd decoctions were in order of 5.88, 7.50, and 8.90, and the total extraction time was 3.93 h. CONCLUSION: According to industry production condition, the best SBE technologic condition is: The pH values of the water for the 3 decoctions are in order of 6.0, 7.5, and 9.0, and the extraction time are 2h, 1h, and 1h, respectively. PMID- 17727071 TI - [Influence of compatibility on content of berberine in Maxingganshi decoction]. AB - OBJECTIVE: To set up the quantitative method of herberine in decoctions prepared from various combinations of Maxingganshi decotion by HPLC and to determine the change of general contents in different decoction. METHODS: The study was designed by L8 (2(7)) orthogonal and to determine the change of general contents in different decoction by HPLC. RESULTS: In full formula remove Glycyrrhiza uralensis group, the contents of L-ephedrine, d-pseudephedrine and the amygdaloside cut down significantly. In full formula remove armeniacae semen group, the content of glycyrrhetic acid cut down significantly. Four chemical composition in full formula group had higher contents. CONCLUSION: Armeniacae semen can decrease the content of L-ephedrine, D-pseudephedrine. Glycyrrhiza uralensis can help decoctum amygdaloside and armeniacae semen can help decoctum glycyrrhizic acid. PMID- 17727072 TI - [Study on the technological process of extraction and clathration for Rhizoma Atractylodis Macrocephalae oil with beta-cyclodextrin]. AB - OBJECTIVE: To study the optimal extraction and clathration technology of Rhizoma Atractylodis Macrocephalae oil in Heweilichang Pill. METHODS: Orthogonal test was employed for selecting the optimum of extraction technology of Rhizoma Atractylodis Macrocephalae oil and the oil extraction rate were used as a index. The optimum including technology was chosen by determining the oil-bearing rate and extract ratio of inclusion compound. The inclusion compound were identified with thin chromatogram. RESULTS: The extraction technology was 10 volumes of water, extracted 6h with thick granula of Rhizoma Atractylodis Macrocephalae. The optimum preparation conditions for clathrate were established as beta-CD: oil was 6: 1, 3. 5 times of water, triturated for 75 minutes. CONCLUSION: The process is feasible and the method can be used for production. PMID- 17727073 TI - Selecting an appropriate scan rate: the ".65 rule". AB - Investigators have discovered that the ratio between a user's reaction time and an appropriate scan rate for that user is approximately .65, which we refer to as "the .65 rule." As part of a larger effort to develop software that automatically adapts the configuration of switch access software, data were collected comparing subject performance with a scan rate chosen using the .65 rule and a scan rate chosen by the user. Analysis of the data indicates that for many people, the .65 rule produces a scan rate that is approximately the same as the average switch press time plus 2 standard deviations. Further analysis demonstrates a relationship between the coefficient of variation (the standard deviation divided by the mean) and error rate. If accurate information is available about the mean, standard deviation, and distribution of a client's switch press time, a scan rate can be chosen that will yield a specific error level. If a rigorous statistical approach is impractical, the .65 rule will generally yield a usable scan rate based on mean press time alone. PMID- 17727074 TI - Test-retest reliability and cross validation of the functioning everyday with a wheelchair instrument. AB - The purpose of this study was to establish the test-retest reliability and content validity of an outcomes tool designed to measure the effectiveness of seating-mobility interventions on the functional performance of individuals who use wheelchairs or scooters as their primary seating-mobility device. The instrument, Functioning Everyday With a Wheelchair (FEW), is a questionnaire designed to measure perceived user function related to wheelchair/scooter use. Using consumer-generated items, FEW Beta Version 1.0 was developed and test retest reliability was established. Cross-validation of FEW Beta Version 1.0 was then carried out with five samples of seating-mobility users to establish content validity. Based on the content validity study, FEW Version 2.0 was developed and administered to seating-mobility consumers to examine its test-retest reliability. FEW Beta Version 1.0 yielded an intraclass correlation coefficient (ICC) Model (3,k) of .92, p < .001, and the content validity results revealed that FEW Beta Version 1.0 captured 55% of seating-mobility goals reported by consumers across five samples. FEW Version 2.0 yielded ICC(3,k) = .86, p < .001, and captured 98.5% of consumers' seating-mobility goals. The cross-validation study identified new categories of seating-mobility goals for inclusion in FEW Version 2.0, and the content validity of FEW Version 2.0 was confirmed. FEW Beta Version 1.0 and FEW Version 2.0 were highly stable in their measurement of participants' seating-mobility goals over a 1-week interval. PMID- 17727076 TI - Review of the use of physical restraints and lap belts with wheelchair users. AB - Wheelchair-related physical restraints, lap belts, and other alternatives are intended to provide safe and adequate seating and mobility for individuals using wheelchairs. Physical restraints and lap belts are also helpful for positioning people in their wheelchairs to reduce the risk of injury during wheelchair tips and falls. However, when used improperly or in ways other than intended, injury or even death can result. Although widely prescribed, little evidence is available to direct professionals on the appropriate use of these restraints and lap belts and for whom these restraints are indicated. The purpose of this study was to conduct a review of available literature from 1966-2006 to identify the risks and benefits associated with lap belts while seated in wheelchairs. Twenty five studies that met the inclusion criteria were reviewed. Nine studies reported the frequency of asphyxial deaths caused by physical restraints, nine studies reported the long-term complication and indirect adverse effects of physical restraints and lap-belt use, and seven studies reported the benefits of physical restraints and lap belts with individuals using wheelchairs. Despite the weak evidence, the results suggest a considerable number of deaths from asphyxia caused by the use of physical restraints occurred each year in the U.S. The majority of the deaths occurred in nursing homes, followed by hospitals, and then the home of the person. Most deaths occurred while persons were restrained in wheelchairs or beds. Based on that, caution needs to be exercised when using restraints or positioning belts. In addition, other seating and environment alternatives should be explored prior to using restraints or positioning belts, such as power wheelchair seating options. Positioning belts may reduce risk of falls from wheelchairs and should be given careful consideration, but caution should be exercised if the individual cannot open the latch independently. Also, the duration of use of the physical restraint should be limited. Therefore, several factors should be considered when devising a better quality of physical restraint services provided by health care professionals. These efforts can lead to improved safety and quality of life for individuals who use wheelchairs. PMID- 17727075 TI - Research into telecommunications options for people with physical disabilities. AB - People with a disability do not have equitable access to the modern telecommunication medium. Many experience difficulty typing, handling the phone, dialing, or answering calls. For those who are unable to speak, the only option is to type messages using whatever functional control site exists on their body. The provision of accessible mobile phones for people with disabilities can significantly improve their quality of life through an increased range of accessible activities, and mobile phones can improve their independence, safety, security and self-esteem. This research was aimed at providing practical ways for people with a disability to participate in the extensive community of home and mobile phone users. The outcomes of 10 participants taking part in the evaluation and trial of off-the-shelf telecommunication options are presented. Nine out of 10 participants showed high to very high results in terms of their overall performance and satisfaction with the use of the telecommunication equipment provided. With the processes and support covering equipment matching, education, training, and delivery, current off-the-shelf solutions can help people with disabilities to effectively communicate with other members of our society and to access the same range of information systems and services enjoyed by able-bodied members of the community. PMID- 17727077 TI - Chevalier Jackson lecture 2006. Concepts and culture of innovation. PMID- 17727078 TI - Arytenoid abduction for dynamic rehabilitation of bilateral laryngeal paralysis. AB - OBJECTIVES: Bilateral laryngeal paralysis results in airway obstruction, but the voice is often nearly normal. Tracheotomy provides an airway and preserves voice. Surgical procedures to statically enlarge the glottis can permit decannulation, but do so at the expense of the voice. Motion analysis in cadaver larynges has demonstrated that adductor and abductor muscles rotate the arytenoid cartilage around different axes. We sought to determine whether external rotation of the arytenoid cartilage could enlarge the airway without abolishing residual phonatory adduction. METHODS: We performed arytenoid abduction in 6 patients with obstructing laryngeal paralysis. A suture was placed in the muscular process and posterior-inferior traction was applied, anchoring the suture to the inferior cornu of the thyroid cartilage. Outcomes were evaluated by assessing airway symptoms, by assessing the voice, and by documentation of laryngeal motion via videolaryngoscopy. RESULTS: Three patients with severe stridor had marked relief of symptoms, and 2 of the 3 tracheotomy-dependent patients were decannulated. Three patients had good voices, 2 had mild breathiness, and 1 was very breathy. CONCLUSIONS: Arytenoid abduction is a promising treatment for relieving airway obstruction in patients with laryngeal paralysis. It has the potential to preserve voice in patients with residual phonatory adduction. PMID- 17727079 TI - Association of anxiety and depression with reported disease severity in patients undergoing evaluation for chronic rhinosinusitis. AB - OBJECTIVES: We sought to determine the impact of psychiatric comorbidity on symptom density and resource utilization in chronic rhinosinusitis (CRS). METHODS: A prospective cohort of patients who sought evaluation of CRS was studied with the Rhinosinusitis Symptom Inventory and the Hospital Anxiety and Depression Scale. Data concerning symptom scores, symptom domains, and psychiatric comorbidity were analyzed to determine the interactions among psychiatric comorbidity, symptom reporting, and resource utilization in CRS. RESULTS: We studied 143 patients (mean age, 43.4 years). Low, moderate, and high levels of anxiety were reported by 48.3%, 25.9%, and 25.9% of patients, respectively. Low, moderate, and high levels of depression were reported by 76.2%, 9.1%, and 14.7%. For the combined psychopathology group, 43.3%, 25.9%, and 30% had low, moderate, and high levels. Patients with high anxiety levels reported significant elevations of oropharyngeal symptoms (p = .013) and total symptoms (p = .030) in comparison with the low group. Patients with high depression levels reported higher oropharyngeal (p = .003), systemic (p = .001), and total symptom (p = .003) scores than did the low group. High combined psychopathology scores were associated with elevated facial, oropharyngeal, and systemic scores (p < .05). Regarding medical utilization, high anxiety levels or high combined psychopathology scores were associated with more frequent physician visits (p < .05). A high level of depression was associated with increased antibiotic use, missed workdays, and physician visits (p < .05). CONCLUSIONS: High levels of anxiety and depression are common in patients who undergo evaluation for CRS. Psychiatric comorbidity is associated with increased symptoms in CRS and increased health-care utilization. Anxiety and depression should be identified in these patients to structure appropriate treatment. PMID- 17727080 TI - Effects of cochlear implantation on gustatory function. AB - OBJECTIVES: Because of the anatomic position of the chorda tympani in the tympanic cavity, the nerve is at risk during cochlear implantation. The aim of this study was to assess changes in taste sensitivity and in self-ratings of gustatory function after surgery. METHODS: Twenty-four patients (mean age, 54 years) who underwent cochlear implantation were investigated. Taste function was tested with a validated test for regional quantitative assessment of sweet, sour, salty, and bitter tastes on each side of the tongue before and 4 days after surgery. RESULTS: The mean taste score was 10.0 (SD, 4.0) before and 8.0 (SD, 4.1) after surgery on the side of the tongue ipsilateral to the operated ear (p = .004). However, only 1 patient reported subjective taste loss due to surgery. Taste testing of the side of the tongue contralateral to the operated ear yielded a score of 10.0 (SD, 4.1) before and 10.9 (SD, 4.5) after surgery (p = .037). Self-ratings of gustatory function did not change significantly as a consequence of the procedure. CONCLUSIONS: Our results indicate that cochlear implantation is a relatively safe procedure regarding taste function. Preoperative testing of gustatory function is recommended, at least in those patients who already have undergone operation on the contralateral ear. PMID- 17727081 TI - Paraneoplastic syndromes in patients with cancer of the larynx and hypopharynx. AB - Paraneoplastic syndromes may be the first sign of a malignancy. They are systemic, nonmetastatic manifestations associated with a variety of malignant neoplasms and occurring in a minority of cancer patients. These associations of symptoms and signs are not directly related to the site or local manifestations of a malignant tumor or its metastases, but their recognition may facilitate the detection of malignancies or recurrences. Paraneoplastic syndromes are categorized into 6 types: dermatologic or cutaneous, endocrine, hematologic, neurologic, osteoarticular or rheumatologic, and ocular. Different oncotypes have rarely been associated with paraneoplastic syndromes in patients with cancer of the larynx and hypopharynx. The world literature has been reviewed. PMID- 17727082 TI - Sphenoid sinus fungal balls. AB - OBJECTIVES: We sought to examine the nature of fungal balls of the sphenoid sinus, in particular the exposure of adjacent skull base structures and the potential for surgical morbidity. METHODS: We retrospectively reviewed our series of 17 cases of sphenoid sinus fungal balls seen between 1998 and 2005 with reference to their diagnosis, radiologic changes, histopathology, and surgical management. RESULTS: Exposed structures included the pituitary fossa, cavernous sinus, and cavernous internal carotid artery, but this exposure did not result in an increase in perioperative complications. Sclerotic thickening of the sinus walls persisted, probably representing a chronic osteitis in response to concurrent bacterial infection. This appeared to be protective against further sinus wall erosions. Wall erosions did not heal. One patient demonstrated what appeared to be invasive fungal disease from a fungal ball. CONCLUSIONS: Sphenoid sinus fungal balls can occur with minimal symptoms in a mainly elderly population and require surgical removal. Sphenoid sinus fungal balls have a low rate of operative morbidity and should be effectively managed by transnasal endoscopic sphenoidotomy alone. PMID- 17727083 TI - Isolated cochlear nerve hypoplasia with various internal auditory meatus deformities in children. AB - OBJECTIVES: We report neuro-otological findings in isolated congenital cochlear nerve hypoplasia with various bony deformities and evaluate relationships between functional impairment and the radiologic dimensions of the internal auditory meatus (IAM). METHODS: We performed imaging and functional analyses on consecutive juvenile or adolescent patients between 2001 and 2005 with "isolated" unilateral hypoplasia of the cochlear nerve, without inner ear anomaly or other deformities. RESULTS: Among 20 patients with unilateral profound deafness who underwent imaging studies, 10 (50%) passed the inclusion criteria. In all affected ears, auditory brain stem responses were absent and the speech discrimination score was very poor (0% to 5%). Distortion product otoacoustic emissions were good in 2 ears, fair in 1 ear, and poor in 7 ears. Caloric responses were absent in 2 ears, reduced in 3 ears, and normal in 5 ears. Inferior vestibular nerve function and facial nerve function were normal in all ears. Distortion product otoacoustic emissions and caloric responses tended to be better in ears with less severe narrowing of the IAM. CONCLUSIONS: The risk of co involvement of the inner ear and superior vestibular nerve functions is higher in the presence of a narrower bony IAM. Cochlear nerve hypoplasia is proposed as one of the most important causes of juvenile unilateral deafness because of its unexpectedly high incidence. PMID- 17727084 TI - Mass psychogenic illness presenting as acute stridor in an adolescent female cohort. AB - OBJECTIVES: We describe a cohort of patients with an unusual presentation of stridor, their evaluation and management, and their outcome. We review the pertinent English-language literature. METHODS: We performed a retrospective review of the records of 12 adolescent patients treated for acute-onset inspiratory stridor at the Departments of Otolaryngology-Head and Neck Surgery and Allergy and Immunology at the University of South Florida and the Department of Speech Pathology at the H. Lee Moffitt Cancer Center and Research Institute. Two additional patients received treatment elsewhere. Demographic, historical, and laboratory data, physical examination findings, and follow-up information were extracted. A review of both the Hillsborough County Department of Health epidemiological report and the English-language literature was performed. RESULTS: Fourteen female patients who attended a local high school developed audible inspiratory noise. Twelve of the 14 were seen at the University of South Florida Ear, Nose and Throat Center. The remaining 2 patients were evaluated by outside otolaryngologists but were included in all reports from the Department of Health. Environmental studies did not find noxious chemical or biological agents in the students' environments to explain the development of the symptoms. Physical and videostroboscopic examination identified two distinct laryngeal findings causing the audible stridor. One involved paradoxical vocal fold movement, and the other, supraglottic mucosal collapse into the airway. All patients underwent rigorous speech pathology intervention and structured treatment with either complete resolution or significant improvement, seen both clinically and on videostroboscopic evaluation. CONCLUSIONS: Audible stridor can arise from numerous disease processes. In the vast majority of presentations it occurs sporadically and on an individual basis. Our cohort is especially unusual because of the sheer number of patients. Our presentation of a case of mass psychogenic illness as the cause of vocal cord dysfunction with additional findings of laryngomalacia within a group of adolescent girls is the first in the English-language literature. The key to the diagnosis is recognition of the disorder and susceptible individuals by using a thorough physical examination with emphasis on the laryngoscopic and videostroboscopic findings. The systematic approach, undertaken by a team including an otolaryngologist, an allergist, a speech pathologist, and an epidemiologist, proved to be effective in the management of this complex disorder and highly unusual situation. PMID- 17727085 TI - Clinical investigation and mechanism of air-bone gaps in large vestibular aqueduct syndrome. AB - OBJECTIVES: Patients with large vestibular aqueduct syndrome (LVAS) often demonstrate an air-bone gap at the low frequencies on audiometric testing. The mechanism causing such a gap has not been well elucidated. We investigated middle ear sound transmission in patients with LVAS, and present a hypothesis to explain the air-bone gap. METHODS: Observations were made on 8 ears from 5 individuals with LVAS. The diagnosis of LVAS was made by computed tomography in all cases. Investigations included standard audiometry and measurements of umbo velocity by laser Doppler vibrometry (LDV) in all cases, as well as tympanometry, acoustic reflex testing, vestibular evoked myogenic potential (VEMP) testing, distortion product otoacoustic emission (DPOAE) testing, and middle ear exploration in some ears. RESULTS: One ear with LVAS had anacusis. The other 7 ears demonstrated air bone gaps at the low frequencies, with mean gaps of 51 dB at 250 Hz, 31 dB at 500 Hz, and 12 dB at 1,000 Hz. In these 7 ears with air-bone gaps, LDV showed the umbo velocity to be normal or high normal in all 7; tympanometry was normal in all 6 ears tested; acoustic reflexes were present in 3 of the 4 ears tested; VEMP responses were present in all 3 ears tested; DPOAEs were present in 1 of the 2 ears tested, and exploratory tympanotomy in 1 case showed a normal middle ear. The above data suggest that an air-bone gap in LVAS is not due to disease in the middle ear. The data are consistent with the hypothesis that a large vestibular aqueduct introduces a third mobile window into the inner ear, which can produce an air-bone gap by 1) shunting air-conducted sound away from the cochlea, thus elevating air conduction thresholds, and 2) increasing the difference in impedance between the scala vestibuli side and the scala tympani side of the cochlear partition during bone conduction testing, thus improving thresholds for bone-conducted sound. CONCLUSIONS: We conclude that LVAS can present with an air bone gap that can mimic middle ear disease. Diagnostic testing using acoustic reflexes, VEMPs, DPOAEs, and LDV can help to identify a non-middle ear source for such a gap, thereby avoiding negative middle ear exploration. A large vestibular aqueduct may act as a third mobile window in the inner ear, resulting in an air bone gap at low frequencies. PMID- 17727086 TI - Hypoglossal-facial nerve anastomosis: a meta-analytic study. AB - OBJECTIVES: A meta-analysis was conducted on the outcome of facial nerve function after hypoglossal-facial nerve anastomosis in humans. The roles of the timing of and the underlying cause for surgery, the type of the repair, and previous facial nerve function in the final result were analyzed. METHODS: Articles were identified by means of a PubMed search using the key words "facial-hypoglossal anastomosis," which yielded 109 articles. The data were pooled from existing literature written in English or French. Twenty-three articles were included in the study after we excluded those that were technical reports, those describing anastomosis to cranial nerves other than the hypoglossal, and those that were experimental animal studies. Articles that reported facial nerve function after surgery and timing of repair were included. Facial nerve function had to be reported according to the House-Brackmann scale. If there was more than 1 article by the same author(s), only the most recent article and those that did not overlap and that matched the above criteria were accepted. The main parameter of interest was the rate of functional recovery of the facial nerve after anastomosis. This parameter was compared among all groups with Pearson's X2 test in the SPSS program for Windows. Statistical significance was set at a p level of less than .05. RESULTS: Analysis of the reports indicates that early repair, before 12 months, provides a better outcome. The severity of facial nerve paralysis does not have a negative effect on prognosis. Gunshot wounds and facial neuroma are the worst conditions for favorable facial nerve recovery after anastomosis. Transection of the hypoglossal nerve inevitably results in ipsilateral tongue paralysis and atrophy. Modification of the anastomosis technique seems to resolve this problem. Nevertheless, the effect of modified techniques on facial reanimation is still unclear, because the facial nerve function results were lacking in these reports. CONCLUSIONS: Hypoglossal-facial nerve anastomosis is an effective and reliable technique that gives consistent and satisfying results. PMID- 17727087 TI - Relationship between sinusitis and adenoid size in pediatric age group. AB - OBJECTIVES: We sought to examine the relationship between adenoid volume and the stage of rhinosinusitis, as well as the relationship between age and adenoid size. METHODS: Forty-two children complaining of nasal discharge, whose paranasal sinus computed tomographic scans had been obtained, were involved in the study. The patients with adenoid enlargement underwent adenoidectomy. The volumes of adenoid vegetation were measured in square centimeters, and paranasal sinus computed tomographic scans were classified according to the Lund-Mackay staging system. RESULTS: No statistically significant difference existed between patients whose Lund-Mackay scores were 0 and those with scores greater than 0. There seems to be no correlation between the Lund-Mackay score and the degree of adenoid vegetation. CONCLUSIONS: Adenoid vegetation may cause nasal discharge that is not necessarily due to sinusitis. We could not find any supportive data for the statement "The greater the adenoid tissue, the more extensive the sinusitis." PMID- 17727088 TI - Up-regulation of protease-activated receptor 2 in allergic rhinitis. AB - OBJECTIVES: We compared the patterns of PAR-2 messenger RNA (mRNA) and protein expression in the nasal mucosa of subjects with and without allergic rhinitis. METHODS: Biopsy specimens were obtained from 10 patients with allergic rhinitis and 10 normal controls. RNA was extracted from the nasal mucosa, and semiquantitative reverse transcription-polymerase chain reaction was performed for PAR-2. Tissue sections were immunostained for PAR-2 by use of specific antibody. RESULTS: The expression levels of PAR-2 mRNA in allergic rhinitis nasal mucosa were significantly up-regulated as compared with those in normal nasal mucosa. PAR-2 immunoreactivity was observed in the epithelium and submucosal glands in both normal controls and subjects with allergic rhinitis. Stronger immunoreactivity for PAR-2 was observed in allergic rhinitis nasal mucosa as compared with normal nasal mucosa. CONCLUSIONS: These results suggest that PAR-2 may be involved in allergic nasal inflammation. PMID- 17727089 TI - [Pathology near the patient]. PMID- 17727090 TI - [Diffuse parenchymal lung disease, multidisciplinary approach and role of pathology]. AB - The diagnostic approach to diffuse parenchymal lung disease (DPLD) and especially to the idiopathic interstitial pneumonias has changed over the last two decades, mostly thanks to the development of high resolution CT. Though far from replacing pathology, this additional tool has contributed to the definition of new and more precise diagnostic criteria especially for idiopathic interstitial pneumonias, integrating data provided by the three main contributors: lung specialist, radiologist and pathologist. The purpose of this article is to review the role of histopathology in the multidisciplinary approach of the diagnosis of DPLD and idiopathic interstitial pneumonias. PMID- 17727091 TI - [The crucial role of the pathologist in renal disease]. AB - The analysis of biopsy specimens by a pathologist allows a precise diagnosis in the majority of cases. This diagnosis needs to be correlated with the relevant clinical information during a multidisciplinary board in order to yield an optimal clinicopathological diagnosis. The staging and the activity of the histological lesions described by the pathologist will significantly contribute to the modality of treatment and will help to estimate the course of the disease and eventually prepare the patient for dialysis and/or transplantation. PMID- 17727092 TI - [The place of the pathologist in the management of tumors of soft tissue]. AB - Soft tissue tumors represent a heterogeneous group of lesions which include benign and malignant (sarcomas) mesenchymal proliferations. Sarcomas are rare and represent a real challenge in terms of diagnosis and therapy for the multidisciplinary medical team. The pathologist has to establish the correct diagnosis by answering several questions: is the lesion benign or malignant? if malignant, is it a sarcoma? and what type of sarcoma is it? He has to inform the clinician regarding the potential presence of prognostic factors. Careful evaluations of surgical margins of the resection specimen or of tumor response to neoadjuvant chemotherapy are additional aspects of the pathologic report. Optimal management of the patient depends on a close collaboration between pathologists, surgeons, radiologists, oncologist and radiotherapists. PMID- 17727093 TI - [The role of pathology in neuromuscular diseases]. AB - Myopathies are rare diseases. They may be genetic (muscular dystrophies, metabolic or congenital myopathies) or acquired (inflammatory, drug-related or toxic myopathies and those due to systemic disease). Muscular abnormalities secondary to affections of the peripheral nervous system or anterior horn are not strictly speaking myopathies. Morphological examination of muscle tissue is the key stage of the diagnostic workup, and crucial in directing patient care. Muscle biopsy analysis takes into account clinical and paraclinical data and requires close collaboration between the clinician and pathologist. Three illustrative examples are presented: a congenital muscular dystrophy, a glycogenosis and a muscular dystrophy mimicking polymyositis. PMID- 17727094 TI - [Breast cancer: pathology, the cornerstone of therapeutic decision]. AB - Tailoring adjuvant therapy in breast cancer patients relies on prognostic and predictive factors, most of which are currently established by histopathological analysis of tumors. The quality of the assessment of the former (i.e.: tumor size, lymph node status, tumor grade, HER2 status, and lymphovascular invasion) and the latter (estrogen and progesteron receptors expression, HER2 overexpression or amplification) is an essential prerequisite for an optimal therapeutic decision. If the prognostic and predictive values of multigenes signatures are confirmed by on-going clinical studies, this approach could enter the clinical practice in the coming years and result in improved accuracy of adjuvant therapies in breast cancer patients. This approach might especially allow avoiding overtreatment in patients at low risk of recurrence. PMID- 17727095 TI - [Pediatric pathology: a child is not an adult in miniature form]. AB - In pediatric pathology, diagnosis explores major aspects of childhood disorders ranging from malformative syndromes to neoplasm's and forensic pathology. For this mental gymnastics, knowledge of the different morphological and physiological process of development and adaptation are essential. Furthermore, new adjuvant technology ensure a more precise diagnosis by the pediatric pathologist. A review of some particular situations in child are illustrated below. PMID- 17727096 TI - [The future of human beings, will it happen outside biology?]. PMID- 17727097 TI - [Stents: controversies, innovations and making waves. Echoes from the American College of Cardiology 2007 (II)]. PMID- 17727098 TI - [H5N1 and the return to the Old Continent]. PMID- 17727099 TI - [A redefinition of the criteria on Alzheimer's]. PMID- 17727100 TI - [The dark backstage of the Metagenex case (II)]. PMID- 17727101 TI - Do "mudsplashes" induce tactile change blindness? AB - The phenomenon of change blindness (the surprising inability of people to correctly perceive changes between consecutively presented displays), primarily reported in vision, has recently been shown to occur for positional changes presented in tactile displays as well. Here, we studied people's ability to detect changes in the number of tactile stimuli in successively presented displays composed of one to three stimuli distributed over the body surface. In Experiment 1, a tactile mask consisting of the simultaneous activation of all seven possible tactile stimulators was sometimes presented between the two to-be discriminated tactile displays. In Experiment 2, a "mudsplash" paradigm was used, with a brief irrelevant tactile distractor presented at the moment of change of the tactile display. Change blindness was demonstrated in both experiments, thus showing that the failure to detect tactile change is not necessarily related to (1) the physical disruption between consecutive events, (2) the effect of masking covering the location of the change, or (3) the erasure or resetting of the information contained within an internal representation of the tactile display. These results are interpreted in terms of a limitation in the number of spatial locations/events that can be consciously accessed at any one time. This limitation appears to constrain change-detection performance, no matter the sensory modality in which the stimuli are presented. PMID- 17727102 TI - Multisensory numerosity judgments for visual and tactile stimuli. AB - To date, numerosity judgments have been studied only under conditions of unimodal stimulus presentation. It is therefore unclear whether the same limitations on correctly reporting the number of unimodal visual or tactile stimuli presented in a display might be expected under conditions in which participants have to count stimuli presented simultaneously in two or more different sensory modalities. In Experiment 1, we investigated numerosity judgments using both unimodal and bimodal displays consisting of one to six vibrotactile stimuli (presented over the body surface) and one to six visual stimuli (seen on the body via mirror reflection). Participants had to count the number of stimuli regardless of their modality of presentation. Bimodal numerosity judgments were significantly less accurate than predicted on the basis of an independent modality-specific resources account, thus showing that numerosity judgments might rely on a unitary amodal system instead. The results of a second experiment demonstrated that divided attention costs could not account for the poor performance in the bimodal conditions of Experiment 1. We discuss these results in relation to current theories of cross-modal integration and to the cognitive resources and/or common higher order spatial representations possibly accessed by both visual and tactile stimuli. PMID- 17727103 TI - Roughness perception in haptic virtual reality for sighted and blind people. AB - Psychophysical functions for perceived roughness, relating ln (magnitude estimate of roughness) to ln (groove width), were obtained for blind and sighted participants in virtual reality using the PHANToM force feedback device. The stimuli were sinusoidal surfaces with groove widths between 0.675 mm and 20.700 mm. Group functions showed a similar nonlinearity to those obtained in physical reality using rigid probes (Klatzky, Lederman, Hamilton, Grindley, & Swendsen, 2003; Lederman, Klatzky, Hamilton, & Ramsay, 1999). Individual functions gave a different picture. Of 23 total participants, there were 13 with wholly descending linear psychometric functions, 7 with quadratic functions similar to the group function, and 3 with anomalous functions. Individual power law exponents showed no significant effects of visual status. All analyses gave a power law exponent close to -0.80. The implications for theories of roughness, methodologies of data analysis, and the design of haptic virtual reality interfaces are considered. PMID- 17727104 TI - Concurrent task performance enhances low-level visuomotor learning. AB - Visuomotor association learning involves learning to make a motor response to an arbitrary visual stimulus. This learning is essential for visual search and discrimination performance and is reliant upon a well-defined neural circuit in the brain that includes the prefrontal cortex and the hippocampal formation. In the present study, we investigated the possible role of attentional processes during such learning using dual-task interference. A motor, verbal, or perceptual concurrent task was performed during the learning/training block of a simple visual discrimination task. Contrary to expectation, the dual-task groups showed improved learning and learning-dependent performance compared with untrained control and non-dual-task trained groups. A second experiment revealed that this effect did not appear to be due to increased arousal level; the inclusion of alerting tones during learning did not result in facilitation. These findings suggest that the engagement of attention, but not arousal, during the acquisition of a visuomotor association can facilitate this learning and its expression. PMID- 17727105 TI - Posttransient shifts in auditory lateralization. AB - Presenting an intense (e.g., 80-dB [SPL]) "transient" (e.g., 50-msec) inducer to the ear reduces the loudness of subsequent signals at or near the frequency of the inducer. In this study, we ask whether similar inducers also affect lateralization. In two experiments, we asked how inducing tones presented to one ear (the exposed ear) affect judgments of the lateral position of subsequent target tones having various interaural intensity differences. In Experiment 1, inducers had the same frequency as the targets, and, as predicted, reduced the tendency to lateralize the targets to the exposed ear. In Experiment 2, the frequency of the inducers and the target differed (different critical bands), thereby eliminating the effect on lateralization. These results are consistent with the hypothesis that inducers temporarily reduce the magnitude of the representation of intensity signals in the frequency region around them and that this reduction occurs, at least partly, peripherally to the site at which binaural intensity differences are encoded. The results imply further that the reduction in loudness previously reported under similar stimulus conditions reflects a more general reduction of intensity-based information in hearing. PMID- 17727106 TI - Perceiving the numerosity of rapidly occurring auditory events in metrical and nonmetrical contexts. AB - Experiment 1 determined the fastest tempo at which participants could tap in synchrony with every nth tone (n = 2 to 9) in an isochronous sequence. Tapping was difficult with every 5th or 7th tone but easy with every 2nd, 4th, or 8th tone, suggesting that evenly divisible groups of n tones are automatically subdivided into equal groups of 2 or 3-a form of auditory subitizing that generates metrical hierarchies commonly found in Western music. Experiments 2 and 3 sought evidence of subitizing and subdivision in timed explicit enumeration of short, rapidly presented tone sequences (n = 2 to 10). Enumeration accuracy decreased monotonically with n. Response time increased monotonically up to n = 5 or 6, but less between 2 and 3 than between 3 and 4. Thus, a single group of 2 or 3 tones perhaps can be subitized, but subdivision of larger groups into subgroups of 2 or 3 tones seems to be specific to a repetitive, metrical context. PMID- 17727107 TI - Feature-based attention influences later temporal perception. AB - We investigated the influence of feature-based visual attention on later temporal perception. Although there is ample evidence that space-based attention modulates temporal perception, it is not known whether feature-based attention also serves this function. The present study combined a visual selection task with a temporal interval production task to determine whether feature-based attention interacted with temporal perception. The results indicated that temporal perception of visual stimuli depended on whether the same stimulus had been attended to or ignored in a previous visual selection task. The temporal production of previously ignored stimuli was longer than the temporal production of either previously attended to or novel stimuli. This is the first demonstration of the effect of feature-based attention on later temporal perception. We concluded that temporal perception is affected by previously ignored stimuli. PMID- 17727108 TI - Unconscious, stimulus-dependent priming and conscious, percept-dependent priming with chromatic stimuli. AB - Using metacontrast masking to suppress the conscious registration of a prime stimulus, Breitmeyer, Ro, and Singhal (2004) showed that color priming produced by a masked prime disk occurs at unconscious stimulus-dependent rather than at percept-dependent levels of visual processing. The current set of experiments compares this type of unconscious stimulus-dependent priming to conscious priming produced by a prime that, in two separate ways, is rendered visible and thus activates percept-dependent visual processes. The results indicate that while the masked prime again acts at a stimulus-dependent level of processing, the unmasked, visible primes additionally act at a later percept-dependent level of processing. PMID- 17727109 TI - Perceptual learning can reverse subliminal priming effects. AB - Masked primes presented prior to a target can result in inverse priming (i.e., benefits on trials in which the prime and the target are mapped onto opposite responses). In five experiments, time-of-task effects on subliminal priming of motor responses were investigated. First, we replicated Klapp and Hinkley's (2002) finding that the priming effect is initially straight (i.e., it benefits congruent trials, in which the prime and targets are mapped onto the same response) or absent, and only later reverses (i.e., faster responses in incongruent than in congruent trials). We show that the presentation of the mask plays a crucial role in this reversal and that the reversal occurs later if the mask pattern is very complex. We suggest that perceptual learning improves the recognition of task-relevant features. Once recognized, these features can trigger the preparation of the alternative response and/or inhibit the prime activated response. These findings support an active role of the mask in priming. PMID- 17727110 TI - The role of location and motion information in the tracking and recovery of moving objects. AB - Observers in a multiple object tracking task can track about four to five independently moving targets among several moving distractors, even if all of the stimuli disappear for a 300-msec gap. How observers reacquire targets following such a gap reveals what kind of information they can maintain for targets. Previous research has suggested that participants maintain minimal information about a set of moving objects--namely, just their present spatial locations. We report five new experiments that demonstrate retention of location information for at least four objects, and extrapolated motion information for around two objects. PMID- 17727111 TI - Deployment of spatial attention to words in central and peripheral vision. AB - Four perceptual identification experiments examined the influence of spatial cues on the recognition of words presented in central vision (with fixation on either the first or last letter of the target word) and in peripheral vision (displaced left or right of a central fixation point). Stimulus location had a strong effect on word identification accuracy in both central and peripheral vision, showing a strong right visual field superiority that did not depend on eccentricity. Valid spatial cues improved word identification for peripherally presented targets but were largely ineffective for centrally presented targets. Effects of spatial cuing interacted with visual field effects in Experiment 1, with valid cues reducing the right visual field superiority for peripherally located targets, but this interaction was shown to depend on the type of neutral cue. These results provide further support for the role of attentional factors in visual field asymmetries obtained with targets in peripheral vision but not with centrally presented targets. PMID- 17727112 TI - Interrupting the cascade: orienting contributes to decision making even in the absence of visual stimulation. AB - Most systematic studies of human decision making approach the subject from a cost analysis point of view and assume that people make the highest utility choice. Very few articles investigate subjective decision making, such as that involving preference, although such decisions are very important for our daily functioning. We have argued (Shimojo, Simion, Shimojo, & Scheier, 2003) that an orienting bias effectively leads to the preference decision by means of a positive feedback loop involving mere exposure and preferential looking. The illustration of this process is a continually increasing gaze bias toward the eventual choice, which we call the gaze cascade effect. In the present study, we interrupt the natural process of preference selection, but we show that gaze behavior does not change even when the stimuli are removed from observers' visual field. This demonstrates that once started, the involvement of orienting in decision making cannot be stopped and that orienting acts independently of the presence of visual stimuli. We also show that the cascade effect is intrinsically linked to the decision itself and is not triggered simply by a tendency to look at preferred targets. PMID- 17727113 TI - Prior experience affects amodal completion in pigeons. AB - In a three-alternative forced-choice task, 4 pigeons were trained to discriminate a target stimulus consisting of two colored shapes, one of which partially occluded the other, from two foil stimuli that portrayed either a complete or an incomplete version of the occluded shape. The dependent measure was the percentage of total errors that the birds committed to the complete foil. At the outset of training, the pigeons committed approximately 50% of total errors to the complete foil, but as training progressed, the percentage of errors to the complete foil rose. When the pigeons were given a second exposure to the initial set of stimuli, they committed 70% of total errors to the complete foil, suggesting that they now saw the complete foil as more similar to the occluded target than the incomplete foil. These results suggest that experience with 2-D images may facilitate amodal completion in pigeons, perhaps via perceptual learning. PMID- 17727114 TI - Shifting attention into and out of objects: evaluating the processes underlying the object advantage. AB - Visual cuing studies have been widely used to demonstrate and explore contributions from both object- and location-based attention systems. A common finding has been a response advantage for shifts of attention occurring within an object, relative to shifts of an equal distance between objects. The present study examined this advantage for within-object shifts in terms of engage and disengage operations within the object- and location-based attention systems. The rationale was that shifts of attention between objects require object-based attention to disengage from one object before shifting to another, something that is not required for shifts of attention within an object or away from a location. One- and two-object displays were used to assess object-based contributions related to disengaging and engaging attention within, between, into, and out of objects. The results suggest that the "object advantage" commonly found in visual cuing experiments in which shifts of attention are required is primarily due to disengage operations associated with object-based attention. PMID- 17727115 TI - Typicality effects in face and object perception: further evidence for the attractor field model. AB - In a previous study, it was shown that a 50/50 morph of a typical and an atypical parent face was perceived to be more similar to the atypical parent face than to the typical parent face (Tanaka, Giles, Kremen, & Simon, 1998). Experiments 1 and 2 examine face typicality effects in a same/different discrimination task in which typical or atypical faces and their 80%, 70%, 60%, and 50% morphs were presented sequentially (Experiment 1) or simultaneously (Experiment 2). The main finding was that in both modes of presentation, atypical morphs were more poorly discriminated than their corresponding typical morphs. In Experiment 3, typicality effects were extended to the perception of nonface objects; in this instance, it was found that 50/50 morphs of birds and cars were judged to be more similar to their atypical parents than to their typical parents. These results are consistent with an attractor field model, in which it is proposed that the perception of a face or object stimulus depends not only on its fit to an underlying representation, but also on the representation's location in the similarity space. PMID- 17727116 TI - Multimodal access to verbal name codes. AB - Congruent information conveyed over different sensory modalities often facilitates a variety of cognitive processes, including speech perception (Sumby & Pollack, 1954). Since auditory processing is substantially faster than visual processing, auditory-visual integration can occur over a surprisingly wide temporal window (Stein, 1998). We investigated the processing architecture mediating the integration of acoustic digit names with corresponding symbolic visual forms. The digits "1" or "2" were presented in auditory, visual, or bimodal format at several stimulus onset asynchronies (SOAs; 0, 75, 150, and 225 msec). The reaction times (RTs) for echoing unimodal auditory stimuli were approximately 100 msec faster than the RTs for naming their visual forms. Correspondingly, bimodal facilitation violated race model predictions, but only at SOA values greater than 75 msec. These results indicate that the acoustic and visual information are pooled prior to verbal response programming. However, full expression of this bimodal summation is dependent on the central coincidence of the visual and auditory inputs. These results are considered in the context of studies demonstrating multimodal activation of regions involved in speech production. PMID- 17727117 TI - After Leas-Cross: is now the time for restraint? PMID- 17727118 TI - Improved monitoring of water-associated cryptosporidiosis in Ireland. PMID- 17727119 TI - Medical assessment of fitness to drive for commercial and private vehicle drivers. AB - At a recent Irish College of General Practitioner's meeting a needs assessment was carried out as regards GP's training and education in the determination of medical 'fitness to drive'. Participants (n-62) in this survey highlighted the following results. Nearly all are involved in certifying people to drive (over 2/3 for commercial drivers). Difficult issues such as the aging driver, the driver who needs particular medication (i.e. centrally acting agents) or driving with visual impairment were highlighted by those surveyed. While 2/3 refer to the Department of the Environment 'Green Book' for guidance on how to determine 'fitness to drive' with regard to national legislation and standards, and a lesser number refer to the UK (DVLA) or other guidelines; all identified a gap in these recommendations and requested greater clarification regarding 'fitness to drive' in Ireland.' (The solutions proposed by the participants to address this deficit could be divided into two main categories. These included: easy access to clear medical guidelines and training with regard to these i.e. publication or website) and the option for case referral to a medical doctor with expertise in transportation medicine. PMID- 17727120 TI - Changing pattern of childhood blindness. AB - All children under the age of 16 who fulfilled the criteria of blindness and low vision as defined by WHO were included in the study. These children were recruited from 1990 to 2004 from all the Ophthalmology Departments of Ireland, National Council of Blind and Visually impaired. Data was collected from history, detailed ocular examination and investigations including CT, MRI, ultrasound and chromosomal analysis. The prevalence of blindness in 2004 was 0.05% compared to 0.02% in 1989. The aetiologies were divided in (1) genetic, (2) prenatal, (3) perinatal, (4) childhood categories. The genetic group was 33% of the total, (15.63%) had albinism (11%) had retinal dystrophies. The perinatal group of 27% optic nerve hypoplasia, structural anomalies like microphthalmos, anophthalmos comprised of 15.85% and cataract (5.47%). The perinatal group was 26%, cortical blindness (17.45%), ROP (5.5%) and the childhood group comprised of 12.4% of the total. The overall prevalence of childhood blindness and low vision was shown to have increased compared to 1989. The most significant observation was the decrease in childhood blindness due to ROP, owing to the early diagnosis and treatment and an increase in brain blindness due to cortical disease and disability. This has been shown in other studies and is due to increased survival of preterm neonate. PMID- 17727121 TI - A survey of asylum seekers' general practice service utilisation and morbidity patterns. AB - To compare Irish asylum seekers to other General Medical Scheme (GMS) patients possessing Irish citizenship in terms of their utilisation of GP services, morbidity patterns and consultation outcomes. A retrospective 1 year study on patient records in two Galway City practices was performed. All asylum seekers who were patients of the two practices were compared with two controls each from a population of GMS patients with Irish citizenship matched for age, sex, and GMS status. Demographic information was recorded. For each consultation over the 12 months the diagnosis using the ICPC coding system' and consultation outcomes were recorded. Data was collected on 171 asylum seekers and 342 Irish citizens. The majority of asylum seekers registered in the two practices were from Nigeria (43.9%). The age of cases ranged from 1 month to 60 years of age with a median of 26. 45.8% were female and 54% male. The mean number of visits per asylum seeker per year was 5.16 (SD 3.12) whereas the mean for Irish Citizens was 2.31 (SD 2.33) (p = 0.0001). Asylum seekers had a significantly higher likelihood of being assigned diagnoses in the disease systems of psychiatry, dermatology, neurology, muscuioskeletal disease, urology, respiratory, ENT, Obstetrics and Gynaecology and gastroenterology. Asylum seekers were five times more likely to be diagnosed with psychiatric illness than Irish citizens. Specifically they had a significantly higher chance of being diagnosed with anxiety (odds ratio = 3.17 [95% CI 1.1,8.68]). Overall, the frequency of prescription as a consultation outcome was higher for asylum seekers. Asylum seekers were prescribed more antibiotics and psychiatric medications but Irish GMS had higher prescription rates for drugs outside of these categories. Referral rates were higher in the asylum seeker group. Asylum seekers attended the GP more frequently than their Irish counterparts. They were more likely to be diagnosed with psychological problems than the Irish. Studies have shown a strong link between psychological illness and being a "frequent attender" in general practice. This could explain the higher than average frequency of attendance in this group. They were more likely to be prescribed antibiotics and psychiatric medications. This study provides the first quantitative data to inform debate regarding the appropriate supply of resources to Irish practices with significant numbers of asylum seekers. PMID- 17727122 TI - Transfer delay audit. AB - The purpose was to determine the average transfer time taken for acute patients to arrive to the medical unit from the time of referral by an A/E officer. We included the first 200 consecutive patients with completed records. 86 were men and 114 women, aged between 14 and 96 years. Transfer time was calculated as the difference from the time of referral by the A/E officer in UCHG to the time of arrival to the medical unit in MPH. The average transfer time for all patients was 91.5 minutes. The longest was in the second (17:00-24:00) interval with a mean of 105 minutes. 26.5% of patients arrived later than 2 hours after referral. Our findings confirm the existence of unacceptably long transfer time for a significant number of patients. Causes for this delay should be searched for to help find and implement solutions. PMID- 17727123 TI - Unsuspected endometrial pathology in the subfertile woman. AB - Routine sampling of the endometrium is not considered necessary in the investigation of female infertility in the presence of normal menstruation. We present the cases of five women diagnosed with endometrial pathology during the course of fertility investigations. Three women had atypical polypoid adenomyoma, one had complex endometrial hyperplasia and one had stage 1 endometrial adenocarcinoma. Only the latter described any abnormality in menstruation. No woman had polycystic ovarian syndrome nor any other reason in her history to suspect endometrial pathology. Two women had abnormal transvaginal ultrasound findings. Atypical polypoid adenomyoma is frequently associated with subfertility. Although usually biologically benign, malignant transformation has been reported. With current trends of increasing obesity and later age at attempted conception, the possibility of discovering endometrial pathology during fertility investigation is likely to increase. We believe that a thorough menstrual history and careful assessment of the endometrium is warranted in all women with fertility problems. A transvaginal pelvic ultrasound should be performed in the follicular (early) phase of the cycle. If this ultrasound examination and the woman's menstrual history are both normal, no further evaluation of the endometrial cavity is routinely required. Sonohysterography is superior to pelvic ultrasound in detecting intracavitary pathology and is thus recommended prior to IVF treatment. Hysteroscopy is the gold standard in the detection of intrauterine pathology and is well tolerated in the office setting. Where abnormality is suspected or detected at screening, futher investigation and concomitant treatment is essential. This is ideally performed via hysteroscopy with endometrial sampling or excision of focally abnormal areas. PMID- 17727124 TI - Maternal folate status and neural tube defects in Ireland: the need for a national food fortification program. AB - To determine the present risk of a Neural Tube Defect [NTD] pregnancy in the caucasian primigravid population in Dublin by comparing the serum folate and red cell folate status of primigravid patients attending the first prenatal booking clinic with data from the late 80's. This Cross-sectional population study looking at blood folate status of over 400 sequential primigravid caucasian women with a singleton pregnancy, booking at less than or equal to 20 weeks gestation. All patients were attending a prenatal booking clinic at the Rotunda Hospital in Dublin during 2003-2004. Comparing serum and red cell folate values in 454 primigravid patients in 2003-4 to values to in a large case-control study based on over 56,000 women attending maternity hospitals in Dublin from 1986 to 1990. Just 13.9% of our patients took periconceptual folate, 33.5% of patients took folate in the first 20 weeks of pregnancy and 58.8% of mothers were taking no folate supplement. Overall, 30% of mothers had RCF levels below 400 ug/L--a level recommended as the minimum value required for protection. NTD risk occurred most frequently amongst patients with RCF levels between 300 and 400 ng/mL. PMID- 17727125 TI - Compliance of acute and long stay geriatric patients with nutritional supplementation. AB - BACKGROUND: Nutritional supplements are prescribed to improve nutritional status, and reduce hospital stays in manourised hospital patients. Clinical benefits are dependant on compliance, the level of which remains unclear. AIMS: To assess compliance levels with oral nutritional supplementation and determine methods to improve compliance. METHODS: Compliance was observed over 10 days by measuring total supplements prescribed and weighing wastage remaining after use. Areas for improvement were identified and implemented for 6 months. Specifically, a distinct supplement administration round was established and those patients requiring assistance with supplement consumption were identified with signage above their beds. Compliance was re-assessed in a sub sample of patients. RESULTS: Thirty seven elderly patients (mean age 85 years; 57% female) prescribed nutritional supplements were studied. Mean compliance was significantly greater in males than females (85.7% vs 74%) and acute wards compared to longstay (89.5% vs. 74.2 Compliance with supplements was significantly greater following intervention (mean 74.2% vs. 93%, p < 0.0001). CONCLUSION: Compliance with nutritional supplementation is variable among institutionalized geriatric patients. Timing of supplementation dispensation and improving staff vigilance can positively affect compliance. PMID- 17727126 TI - Genetically modified food and health--a cause for concern? PMID- 17727127 TI - Nurses await impact of new DH team. PMID- 17727128 TI - 'I often have to calculate children's drug doses based on weight rather than age'. PMID- 17727129 TI - The charity appeal. PMID- 17727130 TI - Nursing behind bars. Interview by Emma Vere-Jones. PMID- 17727131 TI - NICE guidance on management of faecal incontinence. PMID- 17727132 TI - Cardiovascular examination. Part four: auscultation of the heart. PMID- 17727133 TI - Caring for patients who have eating disorders. AB - This article gives an overview of the nurse's role when caring for patients with eating disorders. While mental health nurses are more likely than general nurses to be dealing with patients with eating disorders, such disorders can influence an individual's ability to recover from other illnesses so knowledge of this area is relevant in all settings. PMID- 17727134 TI - Reader developed comprehensive obesity intervention program. PMID- 17727135 TI - A 10-month-old boy with jaundice and abdominal pain. PMID- 17727136 TI - A 3-month-old girl with chest congestion and cough. Diagnosis: bronchogenic cyst. PMID- 17727137 TI - Pediatric immunizations: what's new in 2007. PMID- 17727138 TI - New immunization strategies for preventing infectious diseases in adolescents. PMID- 17727139 TI - Pediatric uses of fluoroquinolone antibiotics. AB - Current data, although incomplete, suggest that pediatric administration of a fluoroquinolone, especially the best-studied ciprofloxacin, is safe. However, many experts have raised concerns regarding the emergence of fluoroquinolone resistant pathogens such as pneumococcus if more children are treated with fluoroquinolones. Examination of the available data suggests that these concerns remain valid. Therefore, most experts continue to advise against expanded pediatric use of fluoroquinolones, except in those selected clinical situations where the benefits clearly outweigh the risks of therapy and there are few other antibiotic choices. PMID- 17727140 TI - Germs on a plane--infectious issues and the pediatric international traveler: what pediatricians should know. PMID- 17727141 TI - Bioterrorism: a clinical reality. PMID- 17727142 TI - [Not Available]. PMID- 17727143 TI - [Not Available]. PMID- 17727144 TI - [Not Available]. PMID- 17727145 TI - [Not Available]. PMID- 17727146 TI - [Not Available]. PMID- 17727147 TI - [Not Available]. PMID- 17727148 TI - [Not Available]. PMID- 17727149 TI - [Not Available]. PMID- 17727151 TI - [Not Available]. PMID- 17727150 TI - [Not Available]. PMID- 17727152 TI - [Not Available]. PMID- 17727153 TI - [Not Available]. PMID- 17727154 TI - [Not Available]. PMID- 17727155 TI - [Not Available]. PMID- 17727156 TI - [Not Available]. PMID- 17727157 TI - Clinical snapshot. Lethargy, hiding, and thoracolumbar pain in a Himalayan cat. PMID- 17727158 TI - Parenteral nutrition: uses, indications, and compounding. AB - Decreased caloric and other nutrient intake can complicate the course of both mild and serious illness. With proper case selection, providing parenteral nutrition (PN) can improve clinical outcome, reduce hospitalization time, and reduce the cost of patient care. Many pharmacy facilities can compound PN formulations; with proper staff training and patient monitoring resources, PN can be administered in many veterinary practices. This article discusses the components of PN formulations as well as the criteria for rational selection of patients to receive PN. PMID- 17727159 TI - Parenteral nutrition: formulation, monitoring, and complications. AB - Because decreased caloric and nutrient intake can complicate the course of both mild and serious illness, parenteral nutrition (PN) is an important feeding modality for patients unable to receive adequate enteral nutrition. Although the effectiveness of PN has not been proven in animals, human studies have shown that using PN in appropriately selected cases can improve clinical outcome, reduce hospitalization time, and even reduce the overall cost of patient care. PN formulations for animals are readily available through pharmacies. This article provides practitioners with basic information on calculating and using PN in patients. Information is also provided on monitoring patients receiving PN as well as ways to identify and overcome common complications in animals receiving PN. PMID- 17727160 TI - Clinical snapshot. Polyuria, polydipsia, and glycosuria in a white rabbit. PMID- 17727161 TI - Environmental enrichment for indoor cats. PMID- 17727162 TI - Prion infectivity. PMID- 17727163 TI - Closing the gap between animals and humans. PMID- 17727164 TI - [Fibromyalgia: between certainty and examination]. PMID- 17727165 TI - ["Fibromyalgia is first a medical syndrome, then a social construction"]. PMID- 17727166 TI - [Diagnostic strategy in presence of diffuse pain]. AB - Fibromyalgia (FM) is not the only diagnosis to be considered in patients suffering from chronic diffuse pain. A certain number of differential diagnoses must be taken into account to avoid overdiagnosing FM or mismanaging patients suffering from alternative causes of diffuse pain. In addition to a carefull history and a thorough clinical examination, a targeted biological assessment needs to be carried out. We review the main differential diagnoses of chronic diffuse pain conditions. In the absence of an alternative etiology, the diagnosis of FM must be considered in presence of a cluster of symptoms associating diffuse pain, asthenia and a certain number of tender points. PMID- 17727167 TI - [Causal attributions in the narratives of patients suffering from fibromyalgia]. AB - Fibromyalgia is a chronic pain syndrome, common in primary care. This article presents some elements of a study based on 65 narratives of patients suffering from fibromyalgia. These narratives showed that patients establish causal links between traumatic events such as death, abuse or accident and fibromyalgia. There is some evidence supporting psychosocial approaches as useful in the clinical management of such complex chronic syndromes. It seems in particular important for the doctor to take into account the subjective experience of his/her patients in order to better understand them and legitimate their suffering, an essential step toward an integrated patient-centred healthcare project. PMID- 17727168 TI - [Medication to treat fibromyalgia?]. AB - The present therapeutic approach is aimed at controlling central sensitisation that is supposed to be the core of fibromyalgia's physiopathological mechanisms. The tricyclic antidepressants have some effects on sleep and the improvement of physical activities. Encouraging results have been observed with the serotonin and noradrenaline reuptake inhibitors such as venlafaxine, milnacipran or duloxetine. New Dopamine D3 receptor agonists as well as the new anticonvulsivants such as gabapentine and pregabalin are equally promising. However the prescription of any medication should take place within a multidisciplinary approach. PMID- 17727169 TI - [Antidepressants and pain]. AB - A balanced inhibition of both serotonin and norepinephrine reuptake is usually evoked to explain the analgesic action of tricyclic and SNRI antidepressants but other mechanisms able to modulate the chronic pain-induced neuroplasticity may occur. Fundamental and clinical experiments are necessary to confirm the traditional monoaminergic hypothesis, to improve the efficacy of SRI and to better define the criteria of choice of antidepressants. These could open on novel therapeutic approaches for the management of chronic neuropathic pains as, for example the medication combination. PMID- 17727170 TI - [Fibromyalgia: how to appreciate work capacity?]. AB - Fibromyalgia is a chronic pain syndrome of which there remains difficult to evaluate the functional repercussion. As in other affections without, or with weak shown organic substrate, the evaluation of the work capacity requires a rigorous approach, which adopts an integrative bio-psycho-social model. Diagnostic classification poses problems insofar as the same syndromic association can result in different diagnoses. The object of this article is to highlight some difficulties related to the coexistence of medical and legal logics which can sometimes be divergent. Generalization, on the legal and administrative side, of simple dichotomic rules, must in no manner lead the physician to make the saving of taking into account the complexity. PMID- 17727171 TI - [Intramural hemorrhage of the thoracic aorta]. AB - Intramural hemorrhage (IMH) of the thoracic aorta is a unique aortic syndrome. It is a spontaneous hemorrhage of the vasa vasorum (small vessels that run in the wall of an artery) in the wall of the aorta without an intimal tear, such as overt aortic dissection. IMH has a similar clinical profile, prognosis and can progress to aortic dissection. CT scan ensures the rapid diagnosis of IMH. Surgical treatment of IMH of the ascending aorta is necessary. PMID- 17727172 TI - [Polycystic ovary syndrome and congenital adrenal hyperplasia: a different entity for comparable phenotypes?]. AB - The phenotypes of the polycystic ovarian syndrome (PCOS) and congenital adrenal hyperplasia syndrome (CAHS) present a number of similarities. The main symptoms of PCOS are obesity, menstrual disorders, hirsutism, and low fertility in which the pituitary and adrenal glands are spared. The CAHS is a group of various entities all characterised by different degrees of malfunction of the 21 hydroxylase (CYP21) enzyme. The consequences are a downfall of the levels of aldosterone and cortisol, and the hyperproduction of adrenal androgen hormones. It is capital to be able to recognise these 2 entities in terms of identification of high risk families because the female foetuses suffering from CAHS will undergo severe virilization of there genitals in utero, which can efficiently be prevented by a administration of corticotherapy to the mother throughout the pregnancy. PMID- 17727173 TI - [Terrorism: the effect on public health and the impact for community medicine]. PMID- 17727174 TI - [Human embryonic stem cells and the failing hearts of rats]. PMID- 17727175 TI - [Some pluripotent stem cells have to be obtained from somatic cells]. PMID- 17727176 TI - [Other places, other customs]. PMID- 17727178 TI - [Facing risk]. PMID- 17727177 TI - [The heavy threat of human biometry (2)]. PMID- 17727179 TI - [Patients with upper abdominal pain and echographically-proven gallstones: start with expectative management]. AB - Three patients, two women aged 33 and 75 years and a 62-year-old man, presented with gallstones and upper abdominal pain due to functional dyspepsia, chronic constipation, and oesophageal spasm, respectively. After a period of watchful waiting, the first patient insisted on having a cholecystectomy, but her complaints persisted. In the second patient, the complaints disappeared after treatment with a bulking agent and magnesium oxide. The third patient received medication as well: a proton-pump inhibitor, prokinetic agents, a calcium antagonist and Helicobacter eradication, and recovered. The presence of gallstones is relatively easy to assess by ultrasound imaging, but the decision whether abdominal symptoms are related to gallbladder stones remains a diagnostic challenge for the clinician. The key question for the family practitioner, gastroenterologist and surgeon is which patients with upper abdominal pain and proven gallbladder stones might benefit from a cholecystectomy. The patients described illustrate that upper abdominal pain is not invariably related to symptomatic gallbladder disease. The published evidence supports initial watchful waiting with additional diagnostic investigation, and cholecystectomy only later if judged to be necessary. PMID- 17727180 TI - [The optimal treatment of chronic heart failure with beta-blockers may be dependent upon the genetic background of the patient]. AB - Pharmacogenetics, which aims at the development of'personal pills', is an attractive field in modern medicine. However, the results obtained in the last few years are somewhat disappointing. Recently, a genetic polymorphism was discovered in the treatment of chronic heart failure with beta-blockers. An in vitro study revealed a hypersensitivity of the Arg389 variant in the beta1 adrenergic receptor to the beta-blocker carvedilol. Interestingly, this polymorphism also has ethnic aspects: the allele frequency of the Arg389 variant is 20% lower in Negroes than in Caucasians. If this result can be confirmed in other studies, one should consider testing for this polymorphism before carvedilol is prescribed. The manufacturer of carvedilol might well consider offering to test the patient's DNA for this polymorphism. PMID- 17727181 TI - [The importance of comprehensive transition of care in women with Turner's syndrome]. AB - Turner's syndrome is the most common chromosomal abnormality in females; it affects 1:2000 live female births. It is the result of the complete or partial absence of one X chromosome. The most frequently occurring clinical features are short stature and ovarian failure. Adults with Turner's syndrome have a reduced life expectancy, mainly due to an increased cardiovascular risk. Other morbidities include hypothyroidism, skeletal problems, renal and gastrointestinal disease, and hearing loss. While most females with Turner's syndrome present during childhood and adolescence, one quarter are diagnosed with primary or secondary amenorrhoea in adulthood. Girls with Turner's syndrome usually receive intensive medical care during childhood. Early diagnosis is important for the prevention and treatment of morbidities, as well as attaining optimum adult height and age-appropriate puberty induction. This requires a multidisciplinary approach for which a protocol has been formulated by the Dutch Advisory Group on Growth Hormone. This protocol also provides the rationale for a structured transition of these patients. The emphasis throughout the transition to adult care is on educating the adolescent with Turner's syndrome, her family and adult care providers. Several follow-up studies indicate that the necessary continuum of care is not optimal. PMID- 17727182 TI - [Turner syndrome in adulthood: the need for multidisciplinary care]. AB - Turner syndrome is the result of the complete or partial absence of one X chromosome. As well as short stature and gonadal dysgenesis, a wide range of abnormalities which may not present themselves until adulthood, are seen in nearly every organ system. Adult women with this syndrome have a reduced estimated life expectancy due to the greatly increased risk of structural abnormalities of the heart and aorta, and of other cardiovascular disease. The latter is due to the higher prevalence of hypertension, type-2 diabetes mellitus and dyslipidaemia. Furthermore, Turner syndrome in adulthood is characterized by infertility and oestrogen substitution is often necessary. Due to the diverse and interconnected nature of these problems, women with Turner syndrome benefit from coordinated medical care provided by a multidisciplinary outpatient team including an internist-endocrinologist, a gynaecologist and a cardiologist. We advise a periodic medical screening of women with this syndrome. PMID- 17727183 TI - [Oncoplastic surgery of the breast: a combination of oncological and plastic surgery]. AB - The term oncoplastic surgery refers to surgery on the basis of oncological principles during which the techniques of plastic surgery are used, mostly for reconstructive and cosmetic reasons. The advantage ofoncoplastic surgery for breast cancer is the possibility of performing a wider excision of the tumour with a good cosmetic result. Oncoplastic surgery is a broad concept that can be used for several different combinations of oncological surgery and plastic surgery: mastectomy and immediate reconstruction of the breast, partial mastectomy and reconstruction, excision of the tumour by reduction mammoplasty, and tumour excision followed by remodelling mammoplasty. Oncoplastic surgery requires careful preoperative planning, which is essential in all forms of breast sparing surgery. Oncoplastic principles can easily be applied to basic breast sparing surgery, but one can also choose to increase the possibilities of breast surgery by organising good cooperation between the oncological surgeon and the plastic surgeon. PMID- 17727184 TI - [Diagnostic image (333). A girl with vulvar pain]. AB - A 9-year-old girl with a 4 year history of vulvar complaints was thought to be sexually abused but eventually appeared to be suffering from a urethral polyp. PMID- 17727185 TI - [Follow-up of adult women with Turner's syndrome in a cohort study in Utrecht]. AB - OBJECTIVE: To evaluate the follow-up of adult women with Turner's syndrome. DESIGN: Cross-sectional study using questionnaires. METHOD: In August 2005 questionnaires were sent to 5 adult women with Turner's syndrome who were known to the Wilhelmina Children's Hospital in Utrecht, The Netherlands. The questions concerned morbidity, follow-up and levels of satisfaction with care and the provision of information about Turner's syndrome. Case notes were also examined. RESULTS: 38 questionnaires were returned, 19 from women aged 17-25 and 19 from women aged 26-42. 7 women had been without medical care for some time and 4 women were not receiving any medical care at the time of the study. The remaining women were being monitored by a general practitioner or one or more medical specialists. 6 of the 38 women were under the care of a cardiologist. 5 women had hypertension. 8 women had a renal malformation and, 5 of them were not having any renal follow-up. 8 women had undergone bone mineral density measurements in the preceding 5 years. The women between 17-25 years of age were more satisfied with the transfer of medical care from childhood to adulthood than those between 26-42 years of age. Most women felt they were well informed about Turner's syndrome. CONCLUSION: Medical care for adult women with Turner's syndrome in our study group was less than optimal. Cardiovascular risks in particular needed more attention. We advocate a multidisciplinary approach for the follow-up of women with Turner's syndrome. PMID- 17727187 TI - [Double-sided juvenile osteochondritis dissecans of the lateral femoral condyle in a 15-year-old boy]. AB - A 15-year-old boy of Turkish origin presented with a painful swollen left knee. An X-ray revealed osteochondritis dissecans of the lateral femoral condyle. Arthrotomy was performed and the fragment was fixated with tissue glue and 2 absorbable pins. Eight months later, a large recurrent osteochondral fragment of the lateral femoral condyle was seen on X-ray. The patient was re-operated, during which operation the fragment was found and fixated with three compression screws. One year after the first operation the patient developed similar complaints in the contralateral knee; this knee also contained osteochondral fragments necessitating surgery. Osteochondritis dissecans of the knee is a multifactorial disease in which part of the cartilage of the femoral condyle becomes unattached from the subchondral stratum, usually on the lateral side of the medial femoral condyle. Initially, an inflammatory reaction was thought to be the cause of osteochondritis dissecans. Because of the lack of white blood cells, a previous trauma is a better explanation for the ultimate loosening of the cartilage. The treatments that are described for osteochondritis dissecans are conservative treatment, operative fixation, with or without subsequent chondrocyte transplantation or osteochondral autograft transplantation, and finally microfracturing. PMID- 17727188 TI - [Allergy to cashew nuts and peanuts]. PMID- 17727189 TI - [Tumors in the gallbladder: a possible differentiation between malignant and benign tumours]. PMID- 17727190 TI - [Hyponatraenmia during a long-distance run: due to excessive fluid intake]. PMID- 17727191 TI - 'Before anything else, my responsibility is to understand nurses' frustration'. Interview by Louise Tweddell. PMID- 17727192 TI - 'We need to elect college members who have different skills and experiences'. PMID- 17727193 TI - Moving BME nurses forward. PMID- 17727195 TI - Detecting and preventing female genital mutilation. PMID- 17727194 TI - Building healthier men. Interview by Emma Vere-Jones. PMID- 17727196 TI - The sense of sight. Part three. Testing vision. PMID- 17727197 TI - Understanding diabetic foot ulcers. 1: Pathophysiology. AB - This is the first part of a two-part unit on diabetic foot ulcers. It describes the pathophysiology, risk factors and signs and symptoms of diabetic foot ulcers. PMID- 17727198 TI - Health care reform. PMID- 17727199 TI - Epidural abscess, discitis and vertebral osteomyelitis caused by Neiserria subflava. AB - Neisseria subflava is generally regarded as commensal flora of the oropharyngeal tract and usually non-pathogenic. There are, however, reports of invasive disease such as bacteremia, endocarditis, sepsis, meningitis, septic arthritis and discitis caused by this organism. This paper presents the first reported case of an epidural abscess caused by Neiserria subflava. PMID- 17727200 TI - Got cholecalciferol? PMID- 17727201 TI - Historical overview of the Cardiovascular Research Institute (CRI) in Sioux Falls. PMID- 17727202 TI - Medical management: time, tools, and tactics. PMID- 17727203 TI - Measuring depression in nursing homes. PMID- 17727204 TI - The Executive Training For Research Application (EXTRA) program: perceptions of the first cohort of fellows. AB - The Canadian Health Services Research Foundation (CHSRF) and partners have created an innovative training program to support health care executives who use research evidence to inform decision-making. This article describes the Executive Training for Research Application (EXTRA) program and the perceptions of its first cohort of fellows (n = 24). Despite challenges in balancing the time required to participate in this trusting learning environment, which encouraged and supported networking, the fellows were able to develop and apply a considerable knowledge base for evidence-informed decision-making. PMID- 17727205 TI - The challenges of evaluating health systems networks: lessons learned from an early evaluation of the Child Health Network for the Greater Toronto Area. AB - This article describes the first system-wide evaluation of the Child Health Network (CHN) for the Greater Toronto Area (GTA), a partnership of 29 community and hospital care providers. The CHN performance evaluation sought to identify the impact of the network on the delivery of maternal, newborn and child health services in the GTA. CHN members identified seven criteria to be evaluated (appropriate care, accessibility, effectiveness, satisfaction, integrated and coordinated care, accountability and affordability) and then collaborated in selecting measurable indicators for each criterion. Data were compiled from administrative data sets, or collected as needed. This undertaking succeeded in providing a comprehensive assessment of the network's performance, identification of strategies to improve outcomes and network sustainability, as well as practical information that will inform the important new field of network evaluation. PMID- 17727207 TI - The WestView Primary Care Network in the first six months: defragmenting the system. AB - The objective of this article is to describe the integration of local primary care services through the development of a primary care network in Alberta. WestView Primary Care Network (WPCN) has the vision of integrating primary care teams into the health system. As a result, WPCN has incorporated integrative primary care teams into its clinical programs. Through its strategy of "defragmentation," WPCN is accomplishing the beginnings of service integration in the local health care context. PMID- 17727206 TI - Encouraging self-care within a primary health care framework. AB - This study was undertaken primarily to evaluate Do I Need to See the Doctor?, a book designed to assist young families to self-manage common health problems. In addition, the study sought to determine whether providing an introductory explanation to the book had an impact on the respondents' perceived usefulness of it. Comparisons of emergency room visits were made for the timeframe of the study and for the previous year. Study results support the book's usefulness in increasing respondents' confidence to make knowledgeable, informed self-care decisions. Providing explanations did not affect the book's usefulness. A link between emergency room visits and the book requires further study. PMID- 17727208 TI - Physician Assistants--a solution to wait times in Canada? AB - Access to medical care is limited in most of Canada, and the population often endures lengthy waiting times to see a physician. The use of new and varied health care providers has been suggested as a means to alleviate the shortage of physicians. This paper reviews the history and role of the Physician Assistant (PA), both in Canada and internationally, and outlines the clinical competencies currently held by this provider to fill the role of a physician extender in our country. PAs' experiences are reported in the Canadian Forces (CF), where they have been employed for many years, and in Manitoba, where they are used as surgical assistants. The potential for the PA to be incorporated into our provincial health care systems will be considered in light of common barriers to Health Human Resources (HHR) strategic implementation. PMID- 17727209 TI - Is it wrong for CCHSE members to accept hospitality from their suppliers? PMID- 17727210 TI - Behind closed doors: domestic violence--101. PMID- 17727212 TI - Tennessee advanced practice nurse compensation survey results 2006-2007. AB - In 2006, representatives from Middle Tennessee Advanced Practice Nurses (MTAPN), Greater Memphis Area Advanced Practice Nurses (GMAAPN), and Northeast Tennessee Nurse Practitioners Association (NETNPA) decided to poll APNs in Tennessee to compare data with the most recent results from the Advance for Nurse Practitioners national NP survey. Every other year, Advance for Nurse Practitioners publishes salary survey results from their survey. Most recently, in January 2006, an average nationwide salary for all APNs was reported at $74,812, with Tennessee's average at $71,068. PMID- 17727214 TI - [The effect of preoperative chemo-radiotherapy in the treatment of locally advanced squamous cell carcinoma in the upper- and middle-thirds of the esophagus]. AB - AIM: The aim of this study was to compare the efficiency of the preoperative combined chemo-radiotherapy in the treatment of locally advanced squamous cell carcinoma in different locations of the oesophagus. METHODS: Between 1997 and 2005, 102 patients with locally advanced (T3-4) squamous cell oesophageal cancer received preoperative chemo-radiotherapy. In 40 cases, the tumour was localised in the upper-third (Group I), while in 62 cases, in the middle-third of the oesophagus (Group II). Survival rates of patients receiving neoadjuvant therapy were compared with a historical control group. In addition, Group I and Group II were compared to each other, as well. RESULTS: survival rate was significantly better after neoadjuvant therapy (p:0.0042) Resection was performed in 70% of the patients from Group I, and in 50% of those complete pathological remission (pCR) was observed. The perioperative morbidity and mortality rates were 43% and 14%, respectively. As far as Group II, 69% of the patients underwent oesophageal resection, with a perioperative mortality of 18% and morbidity rate of 62%. pCR was observed only in 7% of the cases. The median survivals (21 and 22 months) and the R0 resection rates (82 and 84%) were similar in the two groups. The pCR subgroup showed a significantly better survival rate. CONCLUSION: In this study, we demonstrated that preoperative chemo-radiotherapy increases survival in locally advanced oesophageal cancer. A significantly higher rate of complete response was observed in patients with upper-third oesophageal cancer. It seems that this group has superior sensitivity to multimodal treatment; therefore, our results support a new prognostic factor in oesophageal cancer treatment. PMID- 17727215 TI - [Surgical treatment of pulmonary metastases of colorectal cancers]. AB - INTRODUCTION: Results of a retrospective study of patients who underwent pulmonary metastasectomies after colorectal surgery in the last five years are reported here. Prognostic factors are evaluated and analyzed in the context of current literature. MATERIAL AND METHODS: 37 lung resections were performed in 33 patients between 2001 and 2006, the male:female ratio was 19:14. The average age was 61.3 years (49-76). We analyzed the extent of lung resections, disease free intervals (DFI), laterality of the tumours, number and locations of metastases, lymph node involvements and the incidence of resection of hepatic metastases. Altogether, 20 solitary lung metastases were removed and 17 multiple resections were performed. 25 sublobar resections, 11 lobectomies and one pneumonectomy were carried out. 18 patients had right sided, eight patients had left sided and six patients had bilateral disease. 6 of the 33 patients underwent either synchronous or metachronous liver resection for hepatic metastases. RESULTS: Survivals were calculated by the Kaplan-Meier method. The average DFI was 27.6 months. When all patients were considered, the average survival was 28 months. 52% of the patients had a 3-year postoperative survival, if lung metastases were present only. CONCLUSIONS: Patients benefit from surgical removal of lung metastases of colorectal cancer. There were no differences in survival rates between patients who underwent resection of solitary or multiple lung metastases up to seven deposits. However, the average survival was 12 months shorter if hilar/mediastinal lymph nodes were involved. Furthermore, the average survival of six patients with hepatic metastases was 10 months shorter than the rest of the group. There was no benefit of DFI over 24 months. None of the other prognostic factors showed significant difference. PMID- 17727216 TI - [Reconstruction of incisional median hernia with retromuscular mesh and hernial sac]. AB - INTRODUCTION: one of the most frequent complications of a laparotomy is the development of an incisional hernia. Proper surgical technique can somewhat reduce the incidence, but it still remains a common sequel. Application of prolene mesh for the reconstruction of the abdominal wall with tension-free methods has excellent results. PATIENTS AND METHODS: between 2001-2005, 50 abdominal wall reconstructions were performed using prolene mesh in sublay position including the peritoneal sac of the incisional hernia. RESULTS: postoperative complication was found in one case only, namely a haematoma was formed in the rectus sheat possibly due to an injury of a branch of the inferior epigastric artery. The haematoma was managed non-operatively by suction drainage. No postoperative respiratory problems were detected; all we noticed was minimal abdominal pain. Patients were mobilized shortly after the surgery. CONCLUSIONS: application of prolene mesh in sublay position including the hernia sac is an effective alternative procedure for preventing postoperative complications, when large incisional hernias are repaired in median laparotomy scars. PMID- 17727217 TI - [Surgical management of anomalous origin of the left coronary artery from the main pulmonary artery with Takeuchi procedure]. AB - Anomalous origin of the left coronary artery from the main pulmonary artery is a rare form of congenital heart disease. It carries a very poor prognosis with a mortality rate of more than 85% in the first year of life due to severe left ventricular failure. Surgical repair results in progressive improvement of left ventricular function even in patients with a severely damaged myocardium. The current surgical management is to reimplant the anomalous origin of the left coronary artery from the pulmonary artery to the aorta. Historically, ligation of the anomalous origin and a subclavian artery-left coronary artery bypass were carried out. A 20-month-old boy underwent a Takeuchi procedure (a fenestration between the aorta and the main pulmonary artery, an intrapulmonary tunnel between the orifice of anomalous left coronary artery and fenestration, and a pulmonary artery reconstruction), because the reimplantation of the anomalous coronary artery was technically impossible. The success of this procedure was proven by good early result. PMID- 17727218 TI - [To the Editor: Thrombolytic therapy for lower limb artery in vascular surgical practice]. PMID- 17727219 TI - [Internet, Medline, other web-sites, blogs--in surgery]. PMID- 17727220 TI - Taking 2-D to task. Pioneering work on a new patient safety bar coding standard is up for public review by HIBCC. PMID- 17727221 TI - When sunset comes unexpectedly. A race to beat the clock got MaineGeneral medical center the system it needed. PMID- 17727222 TI - Supply chain success. Moving to a new software suite allowed Sisters of Mercy Health System to change a month-long process to a week. PMID- 17727223 TI - One antenna for all. Northwestern goes wireless with GE Enterprise Access single antenna infrastructure. PMID- 17727224 TI - A two-tier solution. Memorial Hospital found it takes two vendors to handle imaging properly--one for PACS and one for storage. PMID- 17727226 TI - A plan for all season. By developing disaster recovery plans, healthcare institutions work to ensure that disasters don't turn into catastrophes. PMID- 17727225 TI - Senate and House mark up HELP. With the Congressional shift, the Senate Committee on Health, Education, Labor and Pensions is working to crystallize healthcare. PMID- 17727227 TI - On shaky ground. With the ever-present threat of earthquakes, having the proper disaster recovery plans in place is key. PMID- 17727228 TI - After the storm. For organizations that made it through Hurricane Katrina, disaster recovery is even more meaningful. PMID- 17727229 TI - Hurricanes, floods and fires. As if natural disasters weren't enough, the middle of the country often contends with funding and staffing issues. PMID- 17727230 TI - Sense of security. While natural disasters may not be top of mind for Northeast CIOs, executives know business continuity must still be a priority. PMID- 17727231 TI - A team approach. Rather than being the responsibility of one individual, EMR governance takes a village. PMID- 17727232 TI - Real-time infection protection. Using real-time surveillance data, payers and providers are averting infection, saving lives and reaping benefits. PMID- 17727233 TI - Successful and scalable storage. St. Mary's Regional Medical Center discovered the key to storage is about more than just space. PMID- 17727234 TI - Profile of improvement. Blue Cross Blue Shield of Kansas discovered significant savings through high-tech, high-touch, high-impact physician profiling. PMID- 17727235 TI - The great data escape. Successfully mining clinical data depends on first constructing a proper data warehouse. PMID- 17727236 TI - Beyond disaster recovery. Disaster recovery has refocused healthcare organizations from "always being ready" to "always being on". PMID- 17727237 TI - Revolving door of identities. With an increasingly mobile workforce, healthcare providers are looking for clear, flexible and well-defined best practices. PMID- 17727238 TI - Building continuity. As hospitals look at ways to secure critical patient data, the question remains: how costly will it be? PMID- 17727239 TI - Quality first. Patient safety and quality of care improvement goals unify caregivers in all types of healthcare provider organizations. PMID- 17727240 TI - Anticoagulant blood factor deficiencies (protein C). AB - Anti-coagulant proteins are essential to maintain blood hemostatis for the supply of oxygen and nutrients to tissue cells and for the removal of toxic by-products from metabolism. Hereditary or acquired deficiencies of Protein C, Protein S, or Antithrombin III can lead to disease states such as deep vein thrombosis (DVT) with the possibility of producing lung emboli. Phenomena named Factor V Lieden can produce a similar pathologic condition. Anti-coagulant deficiencies, including Factor V Lieden, are HIDDEN blood conditions that can allow blood clot development, especially with trauma to the tissue and circulatory system. It is proposed that all children between ages twelve to fourteen be checked hereditary deficiencies and Factor V Lieden complications. This would require the development of inexpensive assay equipment12. The present research focuses on the low cost production of Zymogen Protein C via purification from blood plasma Cohn Fraction IV-1. This process is difficult due to the several Homologous Vitamin K dependent proteins in the blood coagulation cascade. Traditional chromatography (ion exchange) cannot achieve the desired separation. Some more exotic technologies are very expensive so our work proposes to use Immobilized Metal Affinity Chromatography (IMAC). It is hoped to produce a lower cost product that can be used prophylactic ally to treat Protein C deficiencies and possibly other coagulation problems. PMID- 17727241 TI - Hemorheological aspects in the microvasculature of several pathologies. AB - We evaluated morphological changes in several pathologies using computerized videocapillaroscopy, and related hemorheological patterns using the laser assisted optical rotational red cell analyzer (LORCA). In addition, tissue oxygenation was measured using two oximeters with Combi sensors (Periflux 5000, Perimed). The study included four groups of patients (pts) that were compared with a control group. Group A Controls (n=25: 15 males [M] and 10 females [F] aged 36 +/- 3 years); Group B Diabetic pts n=32 (IDDM pts n=20: 12 M and 8 F aged 43 +/- 4 years; NIDDM pts n=12: 6 M and 6 F aged 45 +/- 3 years); Group C Glaucoma pts n=30 (16 M and 14 F aged 42 +/- 5 years); Group D Liver failure pts n=6 (3 M and 3 F aged 44 +/- 5 years); Group E Hypertensive pts n=50 (smokers n=28: 12 M and 16 F aged 40 +/- 4 years, and nonsmokers n=22: 12 M and 10 F aged 38 +/- 3 years). In all patients hemorheological measurements were made using the LORCA (including red blood cell [RBC] deformability and aggregability), morphology was evaluated using computerized videocapillaroscopy (magnification 200 x), and transcutaneous oxygen partial pressure measurements (TcpO2) were made with the Periflux 5000. In patients with diabetic microangiopathy: the capillary loops in 50% (16/32) of these pts showed formations such as 'deer horns', 72% (23/32) showed formations such as 'elephant nose', and in 45% (14/32) formations such as a 'cork screw'; in diabetics with POAD an important capillary rarefaction was found in 26% (9/32) of the pts. In glaucoma patients, in 84% (25/30) we observed 'capillary meandering' and images such as 'a comb'. In patients with more complicated pathology capillary rarefaction was found in 70% (21/30) of the patients. An improvement in the perfusion of non-functional loops was found in deceased patients who had suffered liver failure one week after liver transplantation in 90% (5/6) of the studied cadavers. In non-smoking hypertensives morphological changes were found in 25% (6/22) of the patients, and in hypertensive smokers in 47% (13/28). RBC deformability was detected using LORCA and expressed as the Elongation Index (EI), and RBC aggregability was detected using LORCA and expressed in t 1/2 (seconds) indicating the RBC aggregability peak. Group A controls: EI 0.59 +/- 0.02; t 1/2 3 +/- 1 sec; Group B: IDDM EI 0.55 +/- 0.01; t 1/2 : 2 +/- 0.5 sec p < 0.05; NIDDM EI 0.56 +/- 0.01; t 1/2 2 +/- 0.2 sec p < 0.04; Group C glaucoma: EI 0.56 +/- 0.01; t 1/2 2 +/- 0.3 sec p < 0.05; Group D liver failure: EI 0.56 0.02; t 1/2 2 +/- 0.4 sec p < 0.03; Group E hypertensives: smokers EI 0.56 +/- 0.02; t 1/2 2 +/- 0.6 sec p < 0.04; non-smokers EI 0.57 +/- 0.02; t 1/2 2 +/- 0.6 sec p < 0.04 compared with controls. We also measured the TcpO2 at the dorsum of the right foot as a standard site representing peripheral control of microvasculature perfusion. Group A 96 +/- 11 mmHg; Group B IDDM 74 +/- 9 mmHg p < 0.05; NIDDM 76 +/- 8 mmHg p < 0.05; Group C glaucoma 75 +/- 9 mmHg p < 0.05; Group D liver failure 69 +/- 6 mmHg p < 0.05; Group E hypertensives: smokers 70 +/- 5 mmHg p < 0.05, non-smokers 77 +/- 9 mmHg p < 0.05 compared with controls. This study presents an interesting and complete methodology to evaluate the microcirculation in different pathologies that induce changes in the microvasculature. PMID- 17727242 TI - Clonidine elicits a long-term depression in mucosal red cell flux. AB - OBJECTIVE: To evaluate the impact of clonidine on mucosal red cell flux during baseline sedation with propofol or sevoflurane, respectively. MATERIALS AND METHODS: Six healthy, chronically instrumented dogs for the measurement of cardiac output (CO) were repeatedly studied. During baseline sedation with either propofol (15 mg x kg(-1) x h(-1)) or sevoflurane (1.5 MAC), local tissue cell flux was assessed using laser Doppler flowmetry at the enoral mucosa. After baseline measurements, a bolus of clonidine (2.0 microg/kg) was infused within 1 min. Data are presented as mean +/- SEM; STATISTICS: ANOVA, Scheffe's post hoc test, p < 0.05. RESULTS: Clonidine significantly reduced CO from 75 +/- 4 and 75 +/- 6 ml x kg(-1) x min(-1) (sedation with propofol or sevoflurane, respectively) to 40 +/- 3 and 49 +/- 5 ml x kg(-1) x min(-1), however, with almost complete recovery to baseline after 30 min (70 +/- 4 and 71 +/- 6 ml x kg(-1) x min(-1), NS from baseline). Similarly, clonidine decreased mucosal red cell flux by 44 +/- 8% and 54 +/- 4%. However, mucosal perfusion did not return to baseline (-25 +/- 5% and -27 +/- 3%). CONCLUSIONS: In spite of the rapid return to baseline in systemic perfusion, the mucosal red cell flux of the enoral mucosa remained markedly reduced after a single bolus of clonidine. Given the crucial role of preserved microcirculatory perfusion for an intact mucosal barrier function, our data suggest that clonidine might impair this important mechanism to prevent the translocation of bacteria and endotoxins into the systemic circulation. PMID- 17727243 TI - Real-time, automated, fluorophore mediated multi-cardiac marker biosensing system with nano-metallic particle reagent. AB - Cardiovascular disease (CVD) is the leading cause of death in U.S. Early and accurate diagnosis of CVD is crucial to save many lives, especially for the patients suffering the heart attack. Accurate and fast quantification of cardiac muscle specific biomarkers in the blood enables accurate diagnosis and prognosis and timely treatment of the patients. A prototype of fiber-optic, multi-analyte, immuno-biosensing system integrated with an automatic flow control unit has been in development to quantify four important cardiac markers in blood plasma accurately, rapidly and simultaneously. The validity of the sensor was, however, challenged because the concentrations of two markers are only at tens of picomolar level. Here, plasmon rich nano-metallic particles and selected biocompatible solvents were developed for fluorescence enhancement to improve the sensitivity of our fluorophore mediated biosensing. By applying the nanometal particle and the solvent, the sensitivity of single cardiac marker sensors were increased by 1.5 - 3 times. By using the fluorescence enhancing nano-metallic particle reagents, simultaneous quantification of four cardiac markers in plasma is currently possible, using 3-cm-sensor within 10 minutes at an average signal to-noise ratio of 20. PMID- 17727244 TI - PTEN and NDUFB8 aberrations in cervical cancer tissue. AB - Cervical cancer is one of the world's major health issues. Despite many studies in this field, the carcinogenetic events of malignant conversion in cervical tumours have not been significantly characterised. The first aim of this project was to investigate the mutation status of the tumour suppressor gene- Phosphatase and Tension Homolog (PTEN)--in cervical cancer tissue. The second aim of this study was the analysis in the same cervical cancer tissue for aberrations in the mitochondrial electron transport chain subunit gene NDUFB8, which is localised to the same chromosomal contig as PTEN. The third aim was the evaluation of the potential therapeutic anti-cancer drug 2,4-Thiazolidinediones (TZDs) and its affect in regulating the PTEN protein in a cervical cancer cell line (HeLa). To approach the aims, paraffin-embedded cancerous cervical tissue and non-cancerous cervical tissue were obtained. DNA recovered from those tissues was then used to investigate the putative genomic changes regarding the NDUFB8 gene utilising SYBR Green I Real-Time PCR. The PTEN gene was studied via Dual-Labelled probe Real Time PCR. To investigate the protein expression change of the PTEN protein, HeLa cells were firstly treated with different concentrations of 2,4 Thiazolidinediones and the level of PTEN protein expression was then observed utilising standard protein assays. Results indicated that there were putative copy-number changes between the cancerous cervical tissue and non-cancerous cervical tissue, with regard to the PTEN locus. This implies a potential gain of the PTEN gene in cancerous cervical tissue. With regards to normal cervical tissue versus cancerous cervical tissue no significant melting temperature differences were observed with the SYBR Green I Real-Time PCR in respect to the NDUFB8 gene. A putative up-regulation of PTEN protein was observed in TZD treated HeLa cells. PMID- 17727245 TI - Prediction of surgical site infections after major surgery using visible and near infrared spectroscopy. AB - Final results of an investigation into whether oxygen saturation of tissues (StO2, measured by spectrophotometry) could predict surgical site infections (SSI) after major abdominal surgery are presented. StO2 was measured on the arm and wound site pre-operatively and then at 12, 24 and 48 hours post-operatively. A Whitland Research RM200 was employed as the visible lightguide spectrophotometer. StO2 measurements using this machine were designated SSO2 (skin SO2). A Hutchinson Inspectra Model 325 was used for the near infrared spectroscopy (NIS) measurements. StO2 measurements using this machine were designated MSO2 (muscle SO2). Of 59 patients (38 males, 21 females), 42 healed uneventfully and 17 developed SSI. The overall infection rate was 28.8%. No significant differences were seen in wound SSO2 between outcome groups at any stage. At 12 hours there was a significant difference between the two groups with respect to mean wound MSO2 (A = 58.3 +/- 21.6%, B = 42.2 +/- 16.6%, p = 0.005, 95% confidence interval = 5.26, 26.98). A receiver operating characteristic curve showed that when a wound MSO2 of 53% was chosen as the threshold to classify potential infection a sensitivity of 71% and a specificity 73% (chi-squared test, p = 0.002) was achieved. The use of the near-infrared spectrophotometry as a tool to predict wound infections should be further evaluated and advocated. PMID- 17727246 TI - Application of novel metal nanoparticles as optical/thermal agents in optical mammography and hyperthermic treatment for breast cancer. AB - Low heat (42-45 degrees C) hyperthermia is an effective cancer therapy with few side effects. Well engineered nanoparticles can effectively guide heat to the tumor without damaging the normal tissue. When nano-sized particles are injected to an organ with a tumor, they tend to accumulate in the tumor due to the unorganized nature of its vasculature. Magnetic nanoparticles, such as Fe3O4, are heated by a well selected alternating electromagnetic frequency. At a frequency of 450 KHz or lower, Fe3O4 nanoparticles at a size of 10-30 nm were heated effectively, without heating tissue main components. Gold nanoparticles are known as strong near infrared (NIR) absorbers. Nanogold particles at a diameter of 150 nm were added at 0.01 wt% to the tumor model, placed at depths of 1-2.5 cm, in an optically equivalent experimental breast model. Then the surface of the breast model was scanned with NIR light at 788 nm. The particles in the tumor model increased the optical contrast of the tumor by 1-3.5 dB. Considering that some of the FDA approved MRI contrast agents are made of Fe3O4, gold-coated Fe3O4 particles have a potential to be used as safe optical and thermal markers, allowing seamless breast cancer detection and cancer-specific hyperthermic treatment. PMID- 17727247 TI - Possible mechanisms of improved radiation response by cytotoxic RNase, Onconase, on A549 human lung cancer xenografts of nude mice. AB - The cytotoxic RNase, Onconase (ONC), isolated from amphibian oocytes, was used to study its effect on the radiation response in A549 human NSCLC in vitro and in vivo. In cell culture studies, we found that ONC increased the radiation response by ONC-induced inhibition of O2 consumption (QO2). The occurrence of apoptosis was increased by ONC and was dependent on dosages and time exposure (measured by a Tunnel in situ cell death detection assay). Moreover, ONC inhibited sublethal damage repair (SLDR), confirmed by a split dose experiment. In animal studies, ONC significantly increased the radiation-induced tumor growth delay of A549 tumors in vivo. Using a non-invasive DCE-MRI technology, ONC-induced changes of perfusion were observed in A549 tumors. We concluded that the ONC-induced enhancement in tumor oxygenation was mainly due to the reduction in QO2 rather than an increase in tumor blood flow. This investigation suggests important potential clinical uses of ONC for the treatment of NSCLC cancer patients. PMID- 17727248 TI - Effect of pH and imidazole on protein C purification from Cohn fraction IV-1 by IMAC. AB - Cohn Fraction IV-1 (CFIV-1) is a by-product (often discarded) of a plasma fractionation process. It retains 90% of Protein C (PC) of plasma but contains several coagulants structurally homologous to PC. Of these coagulants, Factor II (FII) has the longest half-life (12 times of PC) and largest quantity (9 times of PC) in CFIV-1. Current purification process for PC is by immunoaffinity chromatography using monoclonal antibodies, which is very expensive. Immobilized metal affinity chromatography (IMAC) is an inexpensive process that uses metal ions to adsorb proteins via their surface histidines. Affinity of PC to the metal ions in IMAC is higher than that of FII because PC has 15 surface histidines and FII has 5. Two important factors in an IMAC process are pH and imidazole concentration. PH controls protonation of histidine, and imidazole, a histidine analog, competitively reacts with metal ions. The effects of pH and imidazole on adsorption and elution of PC and FII during IMAC process were studied. The effect of pH on PC and FII adsorption was similar within the range of 6.0 and 8.0. At concentrations below 15 mM imidazole, little PC or FII eluted. At 15 and 20 mM imidazole 2.5% of PC was eluted, while 20-30% of FII was eluted. PMID- 17727249 TI - Predicting melanoma metastatic potential by optical and magnetic resonance imaging. AB - Accurate prediction of tumor metastatic potential would be helpful in treatment planning and in the design of agents that modify the tumor phenotype. We report that three methods that are potentially transferable to the clinic--dynamic contrast enhanced MRI (DCE MRI), T(1rho)-weighted imaging and low temperature fluorescence imaging (that could be performed on biopsy specimens)--distinguished between relatively indolent (A375P) and aggressive (C8161) metastatic human melanoma xenografts in nude mice, whereas T1 and T2 relaxation time measurements did not. DCE MRI data analyzed by the BOLus Enhanced Relaxation Overview (BOLERO) method in conjunction with concurrent measurements of the arterial input function yielded a blood transfer rate constant (Ktrans) which measures perfusion/permeability, that was significantly higher in the core of the indolent tumor than in the core of the aggressive tumor. Histological staining indicated that aggressive tumors had more blood vascular structure but fewer functional vascular structure than indolent tumors. Indolent tumors exhibited T(1rho), values that were significantly higher than those of aggressive tumors at spin locking frequencies >500 Hz. The mitochondrial redox ratio, Fp/(Fp+NADH), where Fp and NADH are the fluorescence of oxidized flavoproteins and reduced pyridine nucleotides, respectively, of aggressive tumors was much higher (more oxidized) than that of indolent tumors and often showed a bimodal distribution with an oxidized core and a reduced rim. These differences observed between these two types of tumors, one indolent and one aggressive, if generalizable, would be very valuable in predicting human melanoma metastatic potential. PMID- 17727250 TI - Analysis of SDHD and MMP12 in an affected solar keratosis and control cohort. AB - The incidence of Squamous Cell Carcinoma (SCG) is growing in certain populations to the extent that it is now the most common skin lesion in young men and women in high ultraviolet exposure regions such as Queensland. In terms of incidence up to 40% of the Australian population over 40 years of age is thought to possess the precancerous Solar Keratosis (SK) lesion and with a small, but significant, chance of progression into SCC, understanding the genetic events that play a role in this process is essential. The major aims of this study were to analyse whole blood derived samples for DNA aberrations in genes associated with tumour development and cellular maintenance, with the ultimate aim of identifying genes associated with non-melanoma skin cancer development. More specifically the first aim of this project was to analyse the SDHD and MMP12 genes via Dual-Labelled Probe Real-Time PCR for copy number aberrations in an affected Solar Keratosis and control cohort. It was found that 12 samples had identifiable copy-number aberrations in either the SDHD or MMP12 gene (this means that a genetic section of either of these two genes is aberrantly amplified or deleted), with five of the samples exhibiting aberrations in both genes. The significance of this study is the contribution to the knowledge of the genetic pathways that are malformed in the progression and development of the pre-cancerous skin lesion Solar Keratosis. PMID- 17727251 TI - Wyman's equation and oxygen flux through the red cell. AB - Wyman's equation of 1966 describes the facilitation of flux of a reversibly bound substrate such as oxygen, consequent on the translational diffusion of the binding protein (the carrier). While Wyman's equation, or some modification of it such as that by Murray 2, may provide a realistic description of the flux of oxygen through a dilute solution of haemoglobin (see also Wittenburg), it is unlikely to be the complete explanation, nor even the basis, for oxygen transport through the intact red cell. The mature erythrocyte contains approximately 350 g/l haemoglobin, and while this suggests that only 35% of the available water volume is actually occupied by the protein, the remaining 65% is unavailable for protein translational diffusion due to the mutual exclusion of the haemoglobin molecules. For this reason we have examined other possible mechanisms whereby haemoglobin may facilitate the translational diffusion of oxygen within the erythrocyte. Possible alternatives include rotational diffusion by the haemoglobins, intracellular shuffling of haemoglobins due to shape changes by the erythrocyte, and haemoglobin rotations and oxygen exchange consequent on the charge change which accompanies substration and desubstration of the haemoglobin molecule. Finally the dipole interactions are shown to generate significant intermolecular attractions between adjacent haemoglobins. PMID- 17727252 TI - Simultaneous measurement of pO2 and perfusion in the rabbit kidney in vivo. AB - Recently, a combined probe has been developed capable of simultaneous measurement of local tissue pO2 (fluorescence oximetry) and microvascular perfusion (laser Doppler flux) within the same local region. The aim of the current study was to test the utility of these combined probes to measure pO2 and perfusion in the kidney. Studies were performed in anesthetized, artificially ventilated rabbits (n=7). Baseline measurements of renal medullary perfusion and pO2 obtained using combined probes (537 +/- 110 units & 28.7 +/- 6.l mmHg, respectively) were indistinguishable from those obtained using independent probes (435 +/- 102 units & 26.9 +/- 6.4 mmHg). Baseline measurements of renal cortical pO2 were also similar between combined (9.7 +/- 1.6 mmHg) and independent probes (9.5 +/- 2.3 mmHg). Baseline levels of cortical perfusion however, were significantly greater when measured using independent probes (1130 +/- 114 units) compared to combined probes (622 +/- 59 units; P < 0.02). Relative changes in perfusion and pO2 resulting from graded stimulation of the renal nerves were not significantly different when measured using combined probes to those obtained using independent probes. We conclude that combined probes are equally suitable to independent probes for tissue pO2 and microvascular perfusion measurement in the kidney. Our results raise some concerns regarding the accuracy of these OxyLite fluorescence probes for pO2 measurement in the kidney, particularly within the renal cortex. PMID- 17727253 TI - Pseudogenes and the electron transport chain. AB - With the advent of easy access to the human genome sequence, molecular biology techniques to target respirome-specific genes have begun to be exploited in the study of human disorders and in particular human cancers. In some recent publications it would appear that some investigators have inappropriately targeted pseudogenes rather than functional genes. The high transcription level and generally small size of many of the genes in the respirome make them prone to duplications in the form of processed pseudogenes within the human genome. Such genes can be challenging to analyse using standard molecular genetics approaches. In this presentation, we offer an analysis of pseudogenes that have been identified to have significant homology with some elements of the respirome. Other sequence elements such as Alu repeats, which present similar research obstacles, are also discussed. PMID- 17727254 TI - Intratumoral VEGF and FGF1 administration alters tumor growth, vascular density, oxygenation, and expression of MCP-1 and interleukins. AB - The biological and physiological effects of exogenous FGF 1 and VEGF were measured using the KHT murine fibrosarcoma tumor model. Tumor-bearing C3H mice were treated intratumorally with either one or six daily doses of 6 microg/mouse FGF1, VEGF, or saline. Tumors were excised 24 hrs after the final injection. Compared to controls, only FGF1 treatment significantly increased tumor weight and size, and only in the 6 dose group. Both FGF1 and VEGF administration (6 dose) decreased tumor cell hypoxia as detected by EF5 uptake: 85% +/- 5% for FGF1 and 82% +/- 6% for VEGF versus 100% +/- 6% for controls. Decreased tumor cell EF5 staining, however, was not associated with changes in numbers of structural or angiogenic vessels. DiOC7 staining showed a slight decrease in perfused vessel numbers in tumors treated with daily VEGF. Intratumoral injections of FGF1 or VEGF also slightly decreased the tumor tissue chemokine MCP-1, interleukins (IL 1beta, IL-6, and IL-18) mRNA expression, and increased NFkappaB binding without altering Ap-1 binding of IkappaB protein expression. In summary, single pulse exposures of tumors to angiogenic factors had little or no effects on tumor growth or perfusion, while daily exposures stimulated tumor growth through improved tumor oxygenation. This improved vascular function occurs without an increase in vascular density. PMID- 17727255 TI - Nitric oxide in the kidney; direct measurements of bioavailable renal nitric oxide. AB - Increasing efforts have been directed towards investigating the involvement of nitric oxide (NO) for normal kidney function. Recently, a crucial role of NO in the development of progressive renal dysfunction has been reported during diabetes and hypertension. Indirect estimation of renal NO production include urinary nitrite/nitrate measurements, but there are several disadvantages of indirect methods since production and bioavailability of NO rarely coincide. Thus, direct measurement of in vivo NO bioavailability is preferred, although these methods are more time consuming and require highly specialized equipment and knowledge. This review focuses on two techniques for in vivo measurement of bioavailable NO in the kidney. We have applied Whalen-type recessed NO microsensors for measurement of NO in the kidney cortex, whereas the hemoglobin trapping technique seems to be more suitable for NO measurement in the renal medulla. Both methods are robust and reliable, and we discuss advantages and shortcomings of each method. PMID- 17727256 TI - Separation of protein C from Cohn Fraction IV-1 by mini-antibody. AB - Human protein C (PC) is a natural anticoagulant, antithrombotic, anti inflammatory, and anti-apoptotic in the bloodstream. PC deficiency can lead to abnormal blood clot formation inside blood vessels, possibly causing heart attack, stroke, skin necrosis, or even death. PC can be, therefore, a valuable therapeutic with little side effect, unlike the currently used anti-coagulants. To reduce the cost involved in immuno purification of PC from blood plasma, single chain variable fragments (mini-Mab) are being produced by recombinant E. coli using phagemid technique. As an economic means of purifying the PC specific mini-Mab, metal affinity chromatography (IMAC) purification process was also investigated. Then using the purified mini-Mab, the feasibility of PC purification from the Cohn Fraction IV-1 was examined. Cohn Fraction IV-1 is usually a discarded side-stream from the blood plasma fractionation of human serum albumin. It holds 90% of PC in plasma, but is very cheap. Preliminary study of PC purification from the Cohn Fraction IV-1 showed 16% purification yield using mini-Mab immobilized NHS-activated Sepharose. The economic analysis for PC purification using mini-Mab showed that the overall process was found to be tens of times cheaper than that using Mab. PMID- 17727257 TI - The role of ATP sensitive channels in insulin secretion and the implications in persistent hyperinsulinemic hypoglycaemia of infancy (PHHI). AB - Persistent Hyperinsulinemic Hypoglycaemia of Infancy (PHHI) is a metabolic syndrome of unregulated insulin secretion. It is a heterogenous disease with causes linked to mutations of the ATP sensitive potassium channels of the beta cell, as well as to metabolism in the beta cell. 5 candidate genes--ABCC8, KCNJ11, GCK, GLUD1 and SCHAD have been implicated in the disease so far, however the aetiology of the disease remains unknown in up to 50% of all patients. We genotyped 43 subjects with PHHI (20 surgically treated and 23 medically treated) for disease associated mutations in the candidate genes. Mutations on ABCC8 were identified in 16 of the 20 (80%) of the surgically treated patients. One putative mutation was identified in the medically treated cohort. The polymorphism E23K on KCNJ11 that is associated with NIDDM was differentially distributed in the 2 cohorts. We discuss the mutations identified, emphasise the importance of the K ATP channel in physiological processes and discuss the possibility that the disease is caused by mutations in other genes associated with insulin release, glucose metabolism in the beta cell or beta cell apoptosis and survival. We propose that these processes must be explored in order to further our understanding of PHHI. PMID- 17727258 TI - Triptolide alters mitochondrial functions. AB - Triptolide (TPL), a small molecule purified from the herb Tripterygium wilfordii, has potential clinical application for suppression of chronic autoimmune disorders and inhibition of tumor growth. However, its mechanism of action is largely unknown. In this study, the effect of TPL on mitochondria was explored with a panel of molecular probes that detect the alteration of mitochondrial functions. When Lewis lung carcinoma (LLC) cells were treated with different doses of TPL for four hours, impaired mitochondrial functions were detected. This included an increased production of reactive oxygen species, the opening of the transition pore of mitochondria, the depolarization of the mitochondria membrane, the inhibition of the production of ATP and increased release of ATP as well as the induction of apoptosis. It is likely that by impairment of mitochondrial function, TPL exerts its inhibitory effect on growth of tumor and progression of inflammatory disease. PMID- 17727259 TI - Immunohistochemical identification and localization of endogenous endostatin and its related peptides in murine tumors. AB - Endostatin, a fragment of the C-terminal domain of mouse collagen XVIII, is a recently demonstrated endogenous inhibitor of tumor angiogenesis. Although endostatin can be detected in blood and urine of tumor-bearing as well as normal mice, the exact localization of the endogenous protein and its related peptides in tumor tissues is unknown. We used immunohistochemistry and immunoblotting to identify endostatin tissue location and staining patterns in tumor, as well as to determine the differences in the levels of endostatin expression between tumor cells (in vitro) and tumor tissues (in vivo). Using a specific polyclonal antibody against murine endostatin, we quantitatively determined the levels of endostatin in five murine mammary tumors and the KHT sarcoma by Western blotting. The staining patterns for this protein in tumor sections were examined histologically by immunohistochemistry. Our results show that: (1) Endogenous endostatin and its related peptides are widely distributed in all in vivo tumor types tested, but not in most of the cultured tumor cell lines. (2) Endogenous endostatin stained most tumor stromal components, including vessel walls, basement membranes, extracellular spaces, and tumor cells. (3) Staining patterns and localization of endostatin and thrombospondin-1 were similar in these tumor sections. PMID- 17727260 TI - Impact of hypoxic and acidic extracellular conditions on cytotoxicity of chemotherapeutic drugs. AB - In the microenvironment of solid growing tumors, pronounced hypoxia or extracellular acidosis is commonly found. The aim of this study was the analysis of the cytotoxic effect of different chemotherapeutic agents (cisplatin, daunorubicin, docetaxel) under these conditions in vitro. Prostate carcinoma cells (R3327-AT1) were exposed to hypoxia (pO2 < 0.5 mmHg) or extracellular acidosis (pH = 6.6) for 6h. After 3h, cytotoxic drugs were added. The cytotoxic effect was assessed by measuring caspase 3-activity (apoptosis), LDH release (necrosis) and repopulation of the cells after chemotherapy (cell death). Compared to aerobic control conditions, severe hypoxia over 6 h per se led to a slight increase in apoptosis, necrosis and cell death. With all three chemotherapeutic agents, hypoxia led to a reduced (by approx. 25%) caspase 3 activity and a marked increase in necrosis. However, the overall cytotoxicity of the drug was not affected by O2-deficiency. By contrast, during extracellular acidosis, the cytotoxic effect of daunorubicin was reduced by 40%, preferentially due to a marked reduction in apoptosis. With cisplatin and docetaxel no change in overall cell death was detected. However, for daunorubicin the tumor-pH seems to have a strong impact on cytotoxicity. With this chemotherapeutic drug the therapeutic efficacy is markedly reduced in an acidotic environment. PMID- 17727261 TI - Brief exposure to -2 Gz reduces cerebral oxygenation in response to stand test. AB - The aim of the present experiment was to determine whether a single 30 s of exposure to -2 Gz (foot-to-head inertial forces) as orthostatic stress results in altered brain oxygenation control in response to active standing. Cerebral oxygenation (oxy-Hb), cerebral blood volume (CBV), and mean arterial blood pressure at brain level (MAPbrain) were recorded in 12 subjects in supine and then in standing position (10 min), before and after -2 Gz centrifugation. The decrease in oxy-Hb (-5 +/- 9 vs. -9 +/- 10 microM, P < 0.001) and in CBV (-2 +/- 11 vs. -4 +/- 12 microM, P < 0.05) upon standing was more important after -2 Gz centrifugation, with unchanged MAPbrain (-6 +/- 7 vs. -6 +/- 9 mmHg). These findings suggest a downward shift in the static cerebral autoregulation curve. PMID- 17727262 TI - Normal cardiac output, oxygen delivery and oxygen extraction. AB - The total amount of blood flow circulating through the heart, lungs and all the tissues of the body represents the cardiac output. Most individual tissues determine their own flow in proportion to their metabolic rate. The skin is a notable exception where the priority is thermal rather than metabolic. Renal blood flow and metabolic rate are related but plasma flow determines metabolic rate rather than metabolic rate determining blood flow. Brain, heart, skeletal muscle and the splanchnic area all vary their blood flows according to local tissue metabolic rate. Summation of peripheral blood flows constitutes venous return and hence cardiac output. Cardiac output is therefore, largely, determined by the metabolic rate of the peripheral tissues; the heart 'from a flow standpoint, plays a "permissive" role and does not regulate its own output'. This peripheral tissue, largely metabolic, determination of cardiac output has been known for many years. Evidence will be presented that blood flow is scaled according to a tissue specific ratio of oxygen delivery (DO2) to oxygen consumption (VO2). For the brain DO2 is approximately three times VO2, for heart muscle DO2 is 1.5 to 1.6 times VO2 and is very similar for skeletal muscle for moderate exercise. Brain, heart and skeletal muscle have the ability to sustain appropriate blood flow in the face of varying blood pressure within limits--the phenomenon known as 'autoregulation'. "Autoregulation, in regard to arterial blood pressure, has been observed" also "in the kidney" and "modest autoregulation" was observed "in the intestines and liver but not in skin". Guyton et al. have suggested that the term 'auto-regulation' should also include variation of blood flow in proportion to metabolic rate and the compensatory changes in blood flow which occur in the face of varying arterial oxygen content (CaO2). This article gives examples of the very precise compensation for CaO2 change in the form of sustained tissue specific DO2:VO2 ratios (corresponding with tissue specific oxygen extraction, E = VO2/DO2). The adequacy of this adjustment for brain, exercising skeletal muscle and heart is particularly striking; skeletal muscle will, for example when CaO2 is reduced, steal blood supply from nonexercising tissues sustaining its own oxygen delivery at normal levels. PMID- 17727263 TI - Near infra-red spectroscopy and arterial oxygen extraction at altitude. AB - The ratio of oxygenated to total haemoglobin (Hb), or rSO2, obtained by near infrared spectroscopy (NIRS), includes both arterial and venous blood of the region examined. The relationship of arterial oxygen extraction, E, and saturation, SaO2, to rSO2 can be expressed, for normally functioning tissue, as E = 1.39 (1 - rSO2/SaO2). Cerebral E, at rest, is constant at lower altitudes but is reduced at 5000 m. This corresponds to constant values of E for SaO2 values above 90% (approximately). E declines linearly for lower SaO2 values, either including measurement at high altitude or at sea level with a reduced inspiratory oxygen concentration. In addition to measurements of brain NIRS resting oxygen extraction of liver, muscle and kidney have also been calculated from NIRS measurements made, on normal inspired air, at sea level and after acute ascent to 2400 m and 5050 m. At 5050 m E was reduced for all four regions but at 2400 m was the same as at sea level for brain, liver and muscle; for the kidney E was elevated at 2400 m. Cerebral oxygen extraction was calculated for rest and the full range of exercise. It was constant at sea level for the lower levels of exercise and, if the calculated extraction value assumptions still hold at lower SaO2 values, reduced for the higher work rates at intermediate altitudes. The present study confirms constancy of oxygen extraction and hence the ratio of oxygen delivery to oxygen consumption (1/E), within physiological limits, and appears to show where those limits lay and, to some extent, show how matters change beyond ordinary physiological limits. PMID- 17727264 TI - Oxygen delivery at sea level and altitude (after slow ascent to 5000 meters), at rest and in mild exercise. AB - Oxygen delivery (DO2) calculated from cardiac output, haematocrit (Hct) and arterial oxygen saturation (SaO2), has been obtained on six subjects at sea level (London) and after slow ascent to 5000 meters (Chamlang base camp) at rest and during mild exercise (25 watts and 50 watts). Haematocrit was increased in all six subjects at 5000 m and expressed as haemoglobin (Hb) rose from a mean (+/- standard error; SEM) of 13.8 +/- 0.1 g (100 ml)(-1) to 15.8 +/-0.3 g (100 ml)(-1) (t = 6.3, p = 0.0014). SaO2 was almost constant with exercise at sea level (rest 98.5%, 25 w 98.3% and 50 w 98.3%) but declined more steeply with exercise at 5000 m (rest 88.8 +/-0.6%, 25 w 85.4 +/-0.4% and 50 w 84.4 +/- 0.5%). Arterial oxygen content (CaO2) was very similar for 25 watts exercise at altitude (5000 m, 18.1 ml per decilitre--dl) as at sea level (London, CaO2 18.2 ml dl(-1)). At rest CaO2 was higher at altitude (18.8 +/-0.2 ml dl(-1)) than at sea level (18.3 +/- 0.4 ml dl(-1)) and at 50 w CaO2 was lower at altitude (17.9 +/- 0.4 ml dl(-1)) than at sea level (18.2 +/- 0.2 ml dl(-1)). Hence, similar cardiac output values at rest (sea level, 5.0 +/- 0.4 litres min(-1) l min(-1); altitude, 5.6 +/- 0.31 min(-1) ) and at 25 w exercise (sea level, 8.2 +/-0.7 1 min(-1); altitude, 8.3 +/-0 .9 1 min'(-1) resulted in similar values for DO2 at rest (sea level, 0.9 +/-0.1 l min( 1) altitude, 1.0 +/-0.1 l min(-1) and 25 w exercise (sea level, 1.5 +/-0.1 l min( 1) altitude, 1.5 +/- 0.2 l min(-1). For 50 w exercise cardiac output and oxygen delivery were greater at altitude in one subject but were significantly reduced for the remaining five (cardiac output mean difference 3.0 +/- 0.91 min(-1), p = 0.015; DO2 mean difference, 0.56 +/- 0.21 l min(-1) p = 0.028). Acclimatization was therefore adequate to sustain a normal value for oxygen delivery for rest and 25 watts exercise (via compensatory erythropoiesis) but insufficient for 50-watt exercise in five of the six subjects. PMID- 17727265 TI - Increased sensitivity to transient global ischemia in aging rat brain. AB - Transient global brain ischemia induced by cardiac arrest and resuscitation (CAR) results in reperfusion injury associated with oxidative stress. Oxidative stress is known to produce delayed selective neuronal cell loss and impairment of brainstem function, leading to post-resuscitation mortality. Levels of 4-hydroxy 2-nonenal (HNE) modified protein adducts, a marker of oxidative stress, was found to be elevated after CAR in rat brain. In this study we investigated the effects of an antioxidant, alpha-phenyl-tert-butyl-nitrone (PBN) on the recovery following CAR in the aged rat brain. Male Fischer 344 rats (6, 12 and 24-month old) underwent 7-minute cardiac arrest before resuscitation. Brainstem function was assessed by hypoxic ventilatory response (HVR) and HNE-adducts were measured by western blot analysis. Our data showed that in the 24-month old rats, overall survival rate, hippocampal CAl neuronal counts and HVR were significantly reduced compared to the younger rats. With PBN treatment, the recovery was improved in the aged rat brain, which was consistent with reduced HNE adducts in brain following CAR. Our data suggest that aged rats are more vulnerable to oxidative stress insult and treatment with PBN improves the outcome following reperfusion injury. The mechanism of action is most likely through the scavenging of reactive oxygen species resulting in reduced lipid peroxidation. PMID- 17727266 TI - Single breath tracing for carbon dioxide in septic patients with tissue hypoxia. AB - We investigated whether tissue hypoxia in sepsis produces substantial modifications of convective airway washout and consequently of CO2 transit time. Single breath tracing for carbon dioxide (SBT-CO2) was analysed in 18 ICU septic patients. Nine patients had tissue hypoxia events. Using the Hill formula, all tracings were analysed point by point to obtain the time required for CO2 to achieve 50% maximal value and the Fractional Expiratory Time 50 (FET0.5). Hypoxic patients FET0.5 and CO2 clearance were compared with non-hypoxic patients data. In hypoxic group CvCO2, CO2 clearance and FET0.5 values were higher than in non hypoxic group. During the recovery from hypoxia capnographic parameters did not differ from those recorded in the hypoxic period. CO2 clearance, but not FET0.5, correlated with arterial lactate and base excess either in hypoxic or in recovery period. In conclusion in septic patients tissue hypoxia influences CO2 elimination, modifying SB-CO2 tracing and lengthening FET0.5. PMID- 17727267 TI - One-pot microwave-assisted synthesis of a benzopyrano[2,3-c]pyrazol-3(2H)-one library. PMID- 17727268 TI - Design of new plasmepsin inhibitors: a virtual high throughput screening approach on the EGEE grid. AB - Though different species of the genus Plasmodium may be responsible for malaria, the variant caused by P. falciparum is often very dangerous and even fatal if untreated. Hemoglobin degradation is one of the key metabolic processes for the survival of the Plasmodium parasite in its host. Plasmepsins, a family of aspartic proteases encoded by the Plasmodium genome, play a prominent role in host hemoglobin cleavage. In this paper we demonstrate the use of virtual screening, in particular molecular docking, employed at a very large scale to identify novel inhibitors for plasmepsins II and IV. A large grid infrastructure, the EGEE grid, was used to address the problem of large computation resources required for docking hundreds of thousands of chemical compounds on different plasmepsin targets of P. falciparum. A large compound library of about 1 million chemical compounds was docked on 5 different targets of plasmepsins using two different docking software, namely FlexX and AutoDock. Several strategies were employed to analyze the results of this virtual screening approach including docking scores, ideal binding modes, and interactions to key residues of the protein. Three different classes of structures with thiourea, diphenylurea, and guanidino scaffolds were identified to be promising hits. While the identification of diphenylurea compounds is in accordance with the literature and thus provides a sort of "positive control", the identification of novel compounds with a guanidino scaffold proves that high throughput docking can be effectively used to identify novel potential inhibitors of P. falciparum plasmepsins. Thus, with the work presented here, we do not only demonstrate the relevance of computational grids in drug discovery but also identify several promising small molecules which have the potential to serve as candidate inhibitors for P. falciparum plasmepsins. With the use of the EGEE grid infrastructure for the virtual screening campaign against the malaria causing parasite P. falciparum we have demonstrated that resource sharing on an eScience infrastructure such as EGEE provides a new model for doing collaborative research to fight diseases of the poor. PMID- 17727269 TI - Areneruthenium(II) 4-acyl-5-pyrazolonate derivatives: coordination chemistry, redox properties, and reactivity. AB - Areneruthenium(II) molecular complexes of the formula [Ru(arene)(Q)Cl], containing diverse 4-acyl-5-pyrazolonate ligands Q with arene = cymene or benzene, have been synthesized by the interaction of HQ and [Ru(arene)Cl(micro Cl)]2 dimers in methanol in the presence of sodium methoxide. The dinuclear compound [{Ru(cymene)Cl}2Q4Q] (H2Q4Q = bis(4-(1-phenyl-3-methyl-5 pyrazolone)dioxohexane), existing in the RRuSRu (meso form), has been prepared similarly. [Ru(cymene)(Q)Cl] reacts with sodium azide in acetone, affording [Ru(cymene)(Q)N3] derivatives, where Cl- has been replaced by N3-. The reactivity of [Ru(cymene)(Q)Cl] has also been explored toward monodentate donor ligands L (L = triphenylphosphine, 1-methylimidazole, or 1-methyl-2-mercaptoimidazole) and exo bidentate ditopic donor ligands L-L (L-L = 4,4'-bipyridine or bis(diphenylphosphino)propane) in the presence of silver salts AgX (X = SO3CF3 or ClO4), new ionic mononuclear complexes of the formula [Ru(cymene)(Q)L]X, and ionic dinuclear complexes of the formula [{Ru(cymene)(Q)}2L-L]X2 being obtained. The solid-state structures of a number of complexes were confirmed by X-ray crystallographic studies. Their redox properties have been investigated by cyclic voltammetry and controlled potential electrolysis, which, on the basis of their measured RuII/III reversible oxidation potentials, have allowed the ordering of the bidentate acylpyrazolonate ligands according to their electron-donor character and are indicative of a small dependence of the HOMO energy upon the change of the monodentate ligand. This is accounted for by DFT calculations, which show a relevant contribution of acylpyrazolonate ligand orbitals to the HOMOs, whereas that from the monodentate ligand is minor. PMID- 17727270 TI - Optimization of microfluidic fuel cells using transport principles. AB - Microfluidic fuel cells exploit the lack of convective mixing at low Reynolds number to eliminate the need for a physical membrane to separate the fuel from the oxidant. Slow transport of reactants in combination with high catalytic surface-to-volume ratios often inhibit the efficiency of a microfluidic fuel cell. The performance of microfluidic devices that rely on surface electrochemical reactions is controlled by the interplay between reaction kinetics and the rate of mass transfer to the reactive surfaces. This paper presents theoretical and experimental work to describe the role of flow rate, microchannel geometry, and location of electrodes within a microfluidic fuel cell on its performance. A transport model, based on the convective-diffusive flux of reactants, is developed that describes the optimal conditions for maximizing both the average current density and the percentage of fuel utilized. The results show that the performance can be improved when the design of the device includes electrodes smaller than a critical length. The results of this study advance current approaches to the design of microfluidic fuel cells and other electrochemically-coupled microfluidic devices. PMID- 17727271 TI - What is the role of the helical domain of Gsalpha in the GTPase reaction? AB - Structural analysis of Gsalpha shows that it is composed of two domains: the ras like domain (RD) that is conserved in all members of the GTPase superfamily and is homologous to the monomeric G-proteins (e.g., p21ras) and an alpha-helical domain (HD) that is unique to heterotrimeric G-proteins. Little is known about the function of the HD. Recent experiments by Bourne and co-workers, who expressed both the RD and the HD of Gsalpha separately and found that GTP hydrolysis is very slow if only recombinant RD is present but is accelerated when the HD is added, suggest that the HD serves as an intrinsic GTPase-activating protein (GAP). In this work, the GTP hydrolysis in Gsalpha was studied. The results obtained by calculating catalytic effects with and without the HD provide evidence for the role of the HD as a GAP. It is demonstrated that a major part of the catalysis is obtained because of an allosteric influence of the HD on the RD. Structural as well as energetic considerations suggest that the HD confines the RD to a more compact conformation, pushing the phosphate into an orientation where it is further stabilized, thus lowering the overall reaction barrier. The resemblance between the behavior of rasGAP and the HD suggests that the conclusion may be a general conclusion, applicable for all of the G-protein members. PMID- 17727273 TI - Simplified reference wave functions for multireference perturbation theory. AB - A number of simplifications in defining the reference wave functions used in multireference second-order Moller-Plesset perturbation theory (MRMP2) calculations are studied. The usual multiconfigurational orbital optimization is avoided by using Hartree-Fock or Kohn-Sham orbitals; the complete configuration expansion in the active-space orbitals is replaced by a severely truncated expansion, and the spin-component-scaling idea is applied to the multireference perturbation expansion. We assess these approximations to the full procedure by calculating the barrier heights for 15 processes taken from the Zhao-Gonzalez Garcia-Truhlar database. Our results suggest that reliable and relatively cheap reference wave functions for MRMP2 calculations can be obtained from the simplifications introduced here. We hope that this will enable the application of the MRMP2 method to a larger range of chemical systems. PMID- 17727272 TI - Single-molecule structural dynamics of EF-G--ribosome interaction during translocation. AB - EF-G catalyzes translocation of mRNA and tRNAs within the ribosome during protein synthesis. Detection of structural states in the reaction sequence that are not highly populated can be facilitated by studying the process one molecule at a time. Here we present single-molecule studies of translocation showing that, for ribosomes engaged in poly(Phe) synthesis, fluorescence resonance energy transfer (FRET) between the G' domain of EF-G and the N-terminal domain of ribosomal protein L11 occurs within two rapidly interconverting states, having FRET efficiencies of 0.3 and 0.6. The antibiotic fusidic acid increases the population of the 0.6 state, indicating that it traps the ribosome.EF-G complex in a preexisting conformation formed during translation. Only the 0.3 state is observed when poly(Phe) synthesis is prevented by omission of EF-Tu, or in studies on vacant ribosomes. These results suggest that the 0.6 state results from the conformational lability of unlocked ribosomes formed during translocation. An idling state, possibly pertinent to regulation of protein synthesis, is detected in some ribosomes in the poly(Phe) system. PMID- 17727274 TI - Theoretical DFT study of fragmentation and association of heme and hemin. AB - The electronic and geometric structures, energy stability, and normal vibrational frequencies of heme, hemine, and their stepwise fragmentation products (with successive loss of two carboxymethyl, four methyl, and two vinyl peripheral groups) in the states with different multiplicity were calculated using the density functional theory (the B3LYP method) with several basis sets. At the same level, the structure and stability of neutral and positively charged dimers of the ferri- and ferroporphyrines were also computed. The computational results are compared with available experimental data. The trends in the behavior of these properties of heme and hemin are analyzed upon the stepwise fragmentation and association and with a change in the multiplicity and external charge. The structure and energetic stability of complexes of the species with molecular oxygen are discussed. PMID- 17727275 TI - Effects of protonation on the spectroscopic properties of tetrapyridoacridine (TPAC) mono- and dinuclear Ru(II) complexes in their ground and (3)MLCT excited states. AB - The spectroscopic behavior of mono- and dinuclear Ru(II) complexes (P, T, PP and TT, Figure 1) that contain the extended planar ligand tetrapyrido[3,2-a:2',3' c:3' ',2' '-h:2' '',3' ''-j]acridine (TPAC) and either 1,10-phenanthroline (phen) or 1,4,5,8-tetraazaphenanthrene (tap) as ancillary ligands is examined in water and as a function of the pH. These four complexes luminesce in aqueous solution. The analyses of the data in absorption lead to the pKa values in the ground state, and the data in emission show that the excited 3MLCT states are much more basic than the ground state. When the complex contains tap ligands (T and TT), a decrease in pH transforms the luminescent excited basic form into another luminescent excited protonated species, which emits more bathochromically. In contrast, with phen ancillary ligands (P and PP), the protonated excited state does not luminesce. The rate constant of first protonation of the 3MLCT state is diffusion controlled, except for the dinuclear PP complex, whose protonation takes place on the nitrogen of the acridine motif. For P, in which the protonation process is the fastest, it would take place on the nitrogen atoms of the nonchelated phen moiety of the TPAC ligand. These results allow also us to gain information on the localization of the excited electron in the 1MLCT state populated upon absorption as well as in the relaxed 3MLCT emissive state. Moreover as these complexes are interesting for their study with DNA, it can be concluded from these data that a portion of the excited species in interaction with DNA will be protonated. PMID- 17727276 TI - Zero-flux surfaces of the electrostatic potential: the border of influence zones of nucleophilic and electrophilic sites in crystalline environment. AB - The topology of the electrostatic potential varphi(r) has been studied for single molecules using geometries and electron distributions rho(r) determined from high resolution single-crystal X-ray diffraction data. The electrostatic potential gradient nablavarphi(r), which is the negative of the electric field E = nablavarphi, has been represented, revealing the position of zero-flux surfaces and critical points. Local maxima and minima of the electrostatic potential are interpreted in terms of electrophilic and nucleophilic sites, which present influence zones delimited by zero-flux surfaces containing saddle points. The influence zones of the nucleophilic and electrophilic sites define two alternative partitions of the space in disjoint volumes, the completeness of these partitions depending on either the neutral or ionic character of the molecule. The results obtained by using this methodology are useful for the interpretation of the saddle points of the electrostatic potential, which are related to the limits of the influence zones and reveal the path for preferred attack on reactive sites with finite influence zones. PMID- 17727277 TI - The quantum solvation, adiabatic versus nonadiabatic, and Markovian versus non Markovian nature of electron-transfer rate processes. AB - In this work, we revisit the electron-transfer rate theory, with particular interests in the distinct quantum solvation effect and the characterizations of adiabatic/nonadiabatic and Markovian/non-Markovian rate processes. We first present a full account for the quantum solvation effect on the electron transfer in Debye solvents, addressed previously in J. Theor. Comput. Chem. 2006, 5, 685. Distinct reaction mechanisms, including the quantum solvation-induced transitions from barrier crossing to tunneling and from barrierless to quantum barrier crossing rate processes, are shown in the fast modulation or low viscosity regime. This regime is also found in favor of nonadiabatic rate processes. We further propose to use Kubo's motional narrowing line shape function to describe the Markovian character of the reaction. It is found that a non-Markovian rate process is most likely to occur in a symmetric system in the fast modulation regime, where the electron transfer is dominant by tunneling due to the Fermi resonance. PMID- 17727278 TI - Microsolvation of cationic dimers in 4He droplets: geometries of A+2(He)N (A=Li, Na, K) from optimized energies. AB - Ab initio computed interaction forces are employed to describe the microsolvation of the A+2(2Sigma) (A=Li, Na, K) molecular ion in 4He clusters of small variable size. The minimum energy structures are obtained by performing energy minimization based on a genetic algorithm approach. The symmetry features of the collocation of solvent adatoms around the dimeric cation are analyzed in detail, showing that the selective growth of small clusters around the two sides of the ion during the solvation process is a feature common to all three dopants. PMID- 17727279 TI - Mass spectrometry and photoelectron spectroscopy of tetracene cluster anions, (tetracene)n- (n = 1-100): evidence for the highly localized nature of polarization in a cluster analogue of oligoacene crystals. AB - Photoelectron spectroscopy of tetracene cluster anions, (tetracene)n- (n = 1 100), reveals the coexistence of two types of isomers, designated as isomers I and II-1 (n = 10-50) or isomers I and II-2 (n > 60), in a wide size range. The vertical detachment energies (VDEs) of isomer I increase persistently due to polarization and structural relaxation effects, where a monomeric anion core is encompassed with geometrically reorganized neutral molecules. Conversely, a characteristic ion distribution in the mass spectrum of (tetracene)n-ensues from the two-dimensional (2D) herringbone-type ordering of isomer II-1, whose VDEs remain constant at 1.80 eV for n >/= 14. Also, isomer II-2, presumably adopting multilayered structural motifs, exhibits invariable VDEs of 2.0 eV, a manifestation of significant charge screening effects in these isomers. The invariable nature of the VDEs of isomers II-1 and II-2 unambiguously demonstrates a largely localized nature of polarization induced by the excess charge residing in microscopic crystal-like environments. Surprisingly, only 14 tetracene molecules within a 2D herringbone-type layer including an excess charge can provide the charge stabilization energy corresponding to approximately 80% of that of the crystal, and the rest of the energy is provided by polarization of neutral molecules in adjacent layers. PMID- 17727280 TI - Automated N-glycopeptide identification using a combination of single- and tandem MS. AB - We describe Peptoonist, a program that can automatically identify the glycans (sugars) present at each N-glycosylation site of a protein. The input to Peptoonist is a series of mass spectra, both MS and MS/MS, obtained from a liquid chromatography (LC) run of proteolytically digested purified glycoproteins. The program uses MS/MS to identify glycosylated peptides and single-MS to identify the N-glycans present on each of these peptides, at least to the level of monosaccharide composition. We validate the program on an LC run of mouse zona pellucida proteins that had been intensively hand annotated by a human expert. Our program doubled the number of glycopeptide identifications, and also found several possible errors in the hand annotation. In addition, it automatically made most of the same glycan isomer identifications as the expert annotator. PMID- 17727281 TI - Responsive polymer gels: double-stranded versus single-stranded DNA. AB - Cross-linking of polyelectrolytes such as DNA gives gels that are osmotically highly swollen but contract upon addition of electrolytes and, in particular, upon association of oppositely charged cosolutes with the polyelectrolyte chain. The deswelling behavior of cross-linked DNA gels thus reflects the DNA-cosolute interactions and provides a basis for the development of responsive DNA formulations. Gels of both single- and double-stranded DNA have interesting applications, and a comparison between them provides the basis for understanding mechanisms. Denaturation of cross-linked ds-DNA gels was induced by heating them above the melting temperature and then cooling. This process, studied by fluorescence using ethidium bromide, appeared to be reversible when a heating/cooling cycle was performed. The swelling behavior upon addition of different cosolutes, such as metal ions, polyamines, charged proteins, and surfactants, was investigated for different DNA gel samples, including long and short ds-DNA and long and short ss-DNA. The DNA molecular weight was found to have only a slight effect on the deswelling curves, whereas conformation exhibited a pronounced effect. In general, single-stranded DNA gels exhibited a larger collapse in the presence of cations than did double-stranded DNA. This difference was more pronounced with surfactants than with the other cosolutes investigated. The difference between double- and single-stranded DNA was attributed to differences in linear charge density, chain flexibility, and hydrophobicity. For surfactants with different chain lengths, the swelling behavior displayed by ss-DNA can be interpreted in terms of an interplay between hydrophobic and electrostatic interactions, the latter being influenced by polymer flexibility. Increasing hydrophobicity of the network leads to a decreased critical aggregation concentration (cac) for the surfactant/gel complex, as a result of the strengthened hydrophobic attractive force between the surfactant and the gel chain. The swelling of DNA gels appears to be reversible and to be independent of DNA conformation. Surfactant-induced deswelling of DNA gels under some conditions appears to be quite homogeneous, whereas under other conditions, there is a separation into a collapsed region in the outer parts of the gel sample and an inside swollen part. Such "skin" formation is quite different for ss- and ds-DNA, with ss-DNA giving more pronounced skin formation over a wider range of binding ratio, beta. For example, no macroscopic separation into collapsed and swollen regions was observed at intermediate degrees of binding for ds-DNA gels, whereas a dense surfactant-rich surface phase (skin) was found to coexist with a swollen core network for ss-DNA gels with beta>0.5. One explanation for this difference is the large deformation energy required for the compression of the very stiff ds-DNA chains. PMID- 17727282 TI - Dynamics and supramolecular organization of the 1D spin transition polymeric chain compound [Fe(NH2trz)3](NO3)2. Muon spin relaxation. AB - The thermal spin transition that occurs in the polymeric chain compound [Fe(NH(2)trz)3](NO3)2 above room temperature has been investigated by zero-field muon spin relaxation (microSR) over the temperature range approximately 8-402 K. The depolarization curves are best described by a Lorentzian and a Gaussian line that represent fast and slow components, respectively. The spin transition is associated with a hysteresis loop of width DeltaT = 34 K (T1/2 upward arrow = 346 K and T1/2 downward arrow = 312 K) that has been delineated by the temperature variation of the initial asymmetry parameter, in good agreement with previously published magnetic measurements. Zero-field and applied field (20-2000 Oe) microSR measurements show the presence of diamagnetic muon species and paramagnetic muonium radical species (A = 753 +/- 77 MHz) over the entire temperature range. Fast dynamics have been revealed in the high-spin state of [Fe(NH(2)trz)3](NO3)2 with the presence of a Gaussian relaxation mode that is mostly due to the dipolar interaction with static nuclear moments. This situation, where the muonium radicals are totally decoupled and not able to sense paramagnetic fluctuations, implies that the high-spin dynamics fall outside the muon time scale. Insights to the origin of the cooperative effects associated with the spin transition of [Fe(NH(2)trz)3](NO3)2 through muon implantation are presented. PMID- 17727283 TI - Templating mesoporous silica with chiral block copolymers and its application for enantioselective separation. AB - In this paper we describe the synthesis of chiral mesoporous silica based on chiral block copolymers of poly(ethylene oxide) and of d-phenylalanine (PEO-b-D Phe) as a surfactant template. The resulting porous structures are characterized by nitrogen sorption experiments, transmission electron microscopy, and small angle XRD. It is shown that chiral block copolymers of PEO-b-D-Phe are effective as a surfactant template for the preparation of silica materials with highly ordered periodic mesoporous structures of hexagonal symmetry with a pore size of ca. 5 nm and high surface areas of ca. 700 m2/g. The enantioselectivity feature of this porous silica, after the extraction of the chiral copolymers, was examined by selective adsorption of enantiomers and racemic solutions of valine. The selective adsorption was measured by circular dichroism (CD) spectroscopy. A chiral selectivity factor of 2.34 was found with the D enantiomer of valine adsorbed preferably. PMID- 17727284 TI - The strength with which a peptide group can form a hydrogen bond varies with the internal conformation of the polypeptide chain. AB - The strength of the H-bond formed between a dipeptide and a proton acceptor molecule is assessed by correlated ab initio quantum calculations for a broad range of different conformations of the dipeptide. The H-bond energy is very sensitive to the internal (phi,psi) angles, even when the geometry of the H-bond does not vary significantly from one conformation to another. This result indicates that the peptide NH is a much less potent proton donor in certain conformations than in others. In particular, extended conformations of a polypeptide are capable of only weak H-bonds. Thus, the interstrand NH...O H bonds in parallel and antiparallel beta-sheets are expected to be significantly weaker than those found in other conformations, such as helices, ribbons, and beta-bends, even if the H-bond geometries are similar. PMID- 17727285 TI - Type-II core/shell CdS/ZnSe nanocrystals: synthesis, electronic structures, and spectroscopic properties. AB - We report a two-step synthesis of highly luminescent CdS/ZnSe core/shell nanocrystals (emission quantum yields up to 50%) that can produce efficient spatial separation of electrons and holes between the core and the shell (type-II localization regime). Our synthesis involves fabrication of cubic-singony CdS core particles that are subsequently overcoated with a layer of ZnSe in the presence of surfactant-ligands in a noncoordinating solvent. Studies of different growth regime of the ZnSe shell indicate that one approach to obtaining high emission efficiencies is through alloying the CdS/ZnSe interface with CdSe, which leads to the formation of an intermediate ZnCdSe layer with a graded composition. We perform theoretical modeling of these core/shell nanocrystals using effective mass approximation and applying first-order perturbation theory for treating both direct electron-hole coupling and the core/shell interface-polarization effects. Using this model we determine the range of geometrical parameters of the core/shell structures that result in a type-II localization regime. We further applied this model to evaluate the degree of electron-hole spatial separation (quantified in terms of the electron-hole overlap integral) based on measured emission wavelengths. We also discuss the potential applicability of these nanocrystals in lasing technologies and specifically the possibility of single exciton optical gain in type-II nanostructures. PMID- 17727286 TI - Tandem reductive perfluoroalkylation of esters with perfluoroalkyl titanate-type reagents. PMID- 17727287 TI - Rhodamine-based fluorescent thermometer exhibiting selective emission enhancement at a specific temperature range. AB - A simple copolymer, poly(NIPAM-co-RD), consisting of N-isopropylacrylamide (NIPAM) and rhodamine (RD) units, behaves as a fluorescent thermometer exhibiting selective emission enhancement at a specific temperature range in water. PMID- 17727288 TI - Synthesis and photoresponsive properties of a molecularly imprinted polymer. AB - A photoresponsive molecularly imprinted polymer was prepared from a di(ureidoethylenemethacrylate)azobenzene monomer, using a methotrexate analogue as template. Photoisomerization of the 3D crosslinked polymer matrix allowed switching the substrate affinity by altering the geometry and spatial arrangement of the receptor binding sites. As a result, controlled release and uptake of the template (or analogous ligands) were obtained. PMID- 17727289 TI - Cationic rhodium(I)/segphos-catalyzed cycloisomerization of 1,6- and 1,7-diynes in the presence of 1,2-cyclohexanedione. AB - We have developed the first catalytic cycloisomerization of 1,6- and 1,7-diynes leading to trienes and vinylpyrroles by using a cationic rhodium(I)/Segphos complex (2.5-10 mol %) and 1,2-cyclohexanedione (100 mol %). 1,2-Cyclohexanedione may effectively occupy vacant coordination sites and thus promote the present cycloisomerization. PMID- 17727290 TI - Lewis acid mediated reactions of 1-cyclopropyl-2-arylethanones with allenic esters: a facile synthetic protocol for the preparation of dihydrofuro[2,3 h]chromen-2-one derivatives. AB - TMSOTf-mediated reactions of 1-cyclopropyl-2-arylethanones with allenic esters afford a novel method for the synthesis of dihydrofuro[2,3-h]chromen-2-one derivatives in moderate to good yields. This process is a sequential reaction involving a nucleophilic ring-opening reaction of the cyclopropane by H(2)O, two intermolecular aldol-type reactions and one intramolecular aldol-type reaction, a cyclic transesterification, dehydration, and aromatization mediated by Lewis acid. PMID- 17727291 TI - Stereoelectronic effects in diastereoselective formation of fulleroids. AB - The substituent effects on diastereoselective formation of fulleroids in the reactions of C(60) with various unsymmetrical diazoalkanes were investigated. The steric demand on the stereochemical course of reactions dominated the diastereoselectivity for diazoalkanes bearing aliphatic as well as monosubstituted pi-resonating groups, whereas the stereoelectronic effects of coexisting pi-resonating aromatic and cyclopropyl groups played a crucial role in the ring closure of the radical intermediates, overriding the steric demand. PMID- 17727292 TI - Interrupted oligomerization revisited: simple and efficient one-pot multicomponent approach to versatile synthetic intermediates. AB - A novel multicomponent reaction allowing for a one-pot formation of three carbon carbon bonds has been developed. It is based on in situ generation and anionic dimerization of methylenedithiane and produces a versatile synthetic equivalent of 4-hydroxy-1,3-alkanediones which, among other things, offers expeditious one pot access to 3(2H)-furanones. PMID- 17727293 TI - Organocatalytic enantioselective Friedel-Crafts reaction of pyrrole derivatives with imines. AB - A highly enantioselective Friedel-Crafts reaction of pyrrole derivatives with N acyl imines catalyzed by chiral phosphoric acids was developed. The reactions produced the pyrrole derivatives in high yields and enantioselectivity. PMID- 17727296 TI - Mechanistic insight into domain formation and growth in a phase-separated Langmuir-Blodgett monolayer. AB - The mechanism of the formation and growth of phase-separated domains in mixed arachidic acid (C19H39COOH) (AA) and perfluorotetradecanoic acid (C13F27COOH) (PA) monolayer films was investigated through a combination of surface pressure area isotherm measurements and atomic force microscope (AFM) imaging. In the mixed AA-PA monolayer system, distinct discontinuous domains consisting primarily of AA form spontaneously in a surrounding continuous matrix enriched in PA. By varying the monolayer deposition conditions, including temperature, surface pressure, and the mechanical agitation of sample solutions, it was determined that phase-separated nuclei are formed initially in the bulk sample solution and further growth of domains proceeds on the subphase surface via an Ostwald ripening process involving the diffusion of AA from the matrix to the discontinuous domains. In addition, selective dissolution of the arachidic acid followed by in situ AFM imaging has allowed the visualization of the fusion of AA to the phase-separated domains and has highlighted some unusual pattern formation that occurs at low subphase temperatures. PMID- 17727295 TI - Chiral bisformamides as effective organocatalysts for the asymmetric one-pot, three-component strecker reaction. AB - C2-symmetric chiral bisformamides have been shown to catalyze the asymmetric one pot, three-component Strecker reaction, which produced the alpha-amino nitriles in excellent yields (up to 99%) with good enantioselectivities (up to 86% ee). Optically pure products could be obtained after a single recrystallization. A possible transition state (TS 1) has been proposed to explain the origin of asymmetric inductivity and reactivity according to the geometry of catalyst 2a optimized at the B3LYP/6-31G(d) level and the absolute configuration of product 4a. PMID- 17727297 TI - Chemical, electrochemical, and structural stability of low-density self-assembled monolayers. AB - The stability of low-density self-assembled monolayers of mercaptohexadecanoic acid on gold is studied under a variety of storage conditions--air at room temperature, argon at room temperature and 4 degrees C, and ethanol at room temperature. The structural monotony of the low-density monolayers was assessed by monitoring the alkyl chains of LDSAMs by grazing-angle Fourier transform infrared spectroscopy as a function of time. Independently of the storage conditions, both symmetric and asymmetric methylene stretches at 2923 and 2852 cm 1 decreased after 4 weeks to 2919 and 2849 cm-1, respectively. These data suggest an increased ordering of the alkyl chains that is distinctly different from that of conventional high-density monolayers of mercaptohexadecanoic acid included as a reference in this study. As a further extension of this observation, the electrochemical barrier properties of the low-density monolayers were assessed by electrochemical impedance spectroscopy and did not change significantly for any of the storage conditions over a period of 4 weeks. Moreover, X-ray photoelectron spectroscopy was used to assess the chemical changes in the low-density monolayers over time. The chemical composition was essentially unaltered for all storage conditions. Specifically, oxidation of the sulfur headgroup, a common cause of monolayer degradation, was excluded for all test conditions on the basis of XPS analysis. This study confirms excellent storage stability for low-density monolayers under commonly used storage conditions and bridges an important technological gap between these systems and conventional high-density systems. PMID- 17727298 TI - Oil-in-water emulsification induced by ellipsoidal hematite colloids: evidence for hydrolysis-mediated self-assembly. AB - We report on the preparation of a novel type of particle-stabilized oil-in-water emulsions. The emulsification mechanism comprises partial hydrolysis of the oil phase promoted by the alkaline surface of ellipsoidal hematite colloids stabilized by tetramethylammonium hydroxide. This mechanism yields monodisperse oil droplets with embedded single ellipsoidal particles. The emulsions, which are stable for at least several months, can be polymerized by radical initiation, to yield latex-like particles with interesting optical and magnetic properties due to their anisotropic hematite cores. Moreover, we show that complex composite core-shell colloids can be prepared by PMMA growth and silica deposition on polymerized emulsion droplets. Finally, as an example of a possible application for our system, we have measured translational and rotational diffusion coefficients of hematite-stabilized oil droplets by depolarized dynamic light scattering. The latter technique can also be employed to monitor the spontaneous emulsification in time. PMID- 17727299 TI - Preparation of nanosize silica in reverse micelles: ethanol produced during TEOS hydrolysis affects the microemulsion structure. AB - Microemulsions have been widely used as microreactors for the synthesis of nanoparticles and mesoporous materials. The correlation between the microstructure of a microemulsion and the features of the obtained materials is the most intriguing problem. On this point, many investigations have their ground on the structure of the precursor microemulsion, i.e., the system before the reaction takes place. Nevertheless, any reactions usually involve the formation of byproducts (aside from the nanoparticles). Several of these byproducts (e.g., ions, amphiphilic molecules) could modify the microemulsion structure during the course of the reaction. Here we examine the hydrolysis of tetraethoxysilane (TEOS) in the water-in-oil microemulsion hexadecyl-trimethylammonium bromide (CTAB)/pentanol/hexane/water. Conductivity and NMR measurements performed during the course of the reaction, in combination with dynamic light scattering and pulsed field gradient spin-echo NMR investigation performed on the microemulsion upon the addition of ethanol, indicate that a byproduct (ethanol) modifies the microreactor structure. The ethanol produced by the TEOS hydrolysis drives the microemulsion structure from small disconnected reverse micelles toward large connected aggregates until (for high enough ethanol loading) the system phase separates into two coexisting liquid phases (a dense interconnected network and a dilute reverse micellar phase). PMID- 17727300 TI - Single quantum dots as local temperature markers. AB - This work describes noncontact, local temperature measurements using wavelength shifts of CdSe quantum dots (QDs). Individual QDs are demonstrated to be capable of sensing temperature variations and reporting temperature changes remotely through optical readout. Temperature profiles of a microheater under different input voltages are evaluated based on the spectral shift of QDs on the heater, and results are consistent with a one-dimensional electrothermal model. The theoretical resolution of this technique could go down to the size of a single quantum dot using far-field optics for temperature characterizations of micro/nanostructures. PMID- 17727301 TI - Toward full spatiotemporal control on the nanoscale. AB - We introduce an approach to implement full coherent control on nanometer length scales. It is based on spatiotemporal modulation of the surface plasmon polariton (SPP) fields at the thick edge of a nanowedge. The SPP wavepackets propagating toward the sharp edge of this nanowedge are compressed and adiabatically concentrated at a nanofocus, forming an ultrashort pulse of local fields. The profile of the focused waveform as a function of time and one spatial dimension is completely coherently controlled. PMID- 17727302 TI - Elderly-onset systemic lupus erythematosus: prevalence, clinical course and treatment. AB - Systemic lupus erythematosus is an autoimmune multi-system disease of uncertain aetiology with highly variable clinical manifestations. Women of child-bearing age are most often affected; however, approximately 10-20% of cases occur in older patients. Elderly-onset lupus has been defined in various studies as onset of lupus after age 50-65 years. Menopause and changes in cellular immunity with aging may contribute to development of lupus in older adults. Many studies suggest that the clinical and serological features of elderly-onset lupus differ from those of lupus in younger patients. Arthritis, fever, serositis, sicca symptoms, Raynaud's syndrome, lung disease and neuropsychiatric symptoms are more common in patients with elderly-onset lupus, while malar rash, discoid lupus and glomerulonephritis are less common in elderly-onset patients compared with younger lupus patients. Most elderly-onset lupus patients have a positive anti nuclear antibody test, but the prevalence of anti-double-stranded DNA and hypocomplementaemia is lower in elderly-onset patients than in younger patients. Rheumatoid factor, anti-Ro/Sjogren's syndrome (SS) A and anti-La/SSB are more often positive in elderly-onset patients. The diagnosis of elderly-onset lupus may be delayed for many months: insidious onset, low prevalence and similarity to other more common disorders make the diagnosis of lupus challenging in this population. Treatment of lupus in the elderly may be complicated by co morbidities and increased risk of toxicities from usual treatments. Optimal management of elderly-onset lupus is empiric because of a lack of randomised controlled studies. However, the approach to treatment is similar regardless of the age of the patient. This article discusses the prevalence, clinical course, serological features, prognosis and treatment of elderly-onset systemic lupus erythematosus. PMID- 17727303 TI - Membranous nephropathy in the older adult: epidemiology, diagnosis and management. AB - Membranous nephropathy is the most important cause of the nephrotic syndrome in elderly patients (aged >65 years). The clinical presentation is similar in older and younger patients, although elderly patients more often present with renal failure. Notably, glomerular filtration rate (GFR) is usually lower in the elderly due to the physiological decline in GFR after the age of 30 years. Secondary causes, especially malignancies, are more common in older patients with membranous nephropathy. Therefore, elderly patients should undergo a thorough examination to exclude a secondary cause. The prognosis of elderly patients with idiopathic membranous nephropathy is not very different from that of younger patients. All elderly patients should receive symptomatic treatment aimed at reducing hypertension, oedema, proteinuria and hyperlipidaemia. It is recommended that elderly patients with a low serum albumin (<2 g/dL) receive prophylactic anticoagulation because of a high risk for thrombosis. Immunosuppressive therapy should be reserved for elderly patients at high risk of progression to end-stage renal disease because the elderly are particularly prone to the adverse effects and infectious complications of immunosuppressive therapy. High-risk elderly patients are characterised by renal insufficiency (GFR <45 mL/min/1.73m(2)), an increase in serum creatinine of >25% or a severe persistent nephrotic syndrome not responding to symptomatic treatment. In addition, elderly patients with a relatively normal GFR (>or=45 mL/min/1.73m(2)) and high urinary excretion of beta(2)-microglobulin and IgG are also at increased risk of developing end-stage renal disease; however, the deterioration in renal function is usually a slow process. Therefore, such patients benefit from immunosuppressive therapy only if their life expectancy is good. If immunosuppressive therapy is started, first line treatment consists of prednisone and cyclophosphamide. If cyclophosphamide is contraindicated or fails to induce a remission, ciclosporin could be used. Treatment with ciclosporin should be limited to patients with a relatively normal renal function (GFR >60 mL/min/1.73m(2)) in view of its nephrotoxicity in patients with renal dysfunction. PMID- 17727305 TI - Pharmacological management of cancer pain in the elderly. AB - Existing studies indicate a high prevalence rate and poor management of cancer pain in the elderly. Pain is often considered an expected concomitant of aging, and older patients are considered more sensitive to opioids. Despite the well known pharmacokinetic changes in the elderly, the complex network of factors involved in the opioid response make the evaluation of a single element, such as age, more difficult. Notwithstanding such difficulties, appropriate analgesic treatment is able to control cancer pain in the elderly in most cases. Skills necessary to optimise pain control in older cancer patients include the ability to objectively assess functional age (not necessarily related to chronological age since the rate of decline is variable), understand the impact of coexisting conditions, carefully manage the numbers and types of drugs taken at the same time and adequately communicate with patients and relatives. The most common treatment of cancer pain consists of the use of regularly given oral analgesics. The elderly are at increased risk of developing toxicity from NSAIDs, and the overall safety of these drugs in frail elderly patients should be considered. When older patients have clear contraindications to NSAIDs, manifest signs of toxicity from these agents, or find that pain is no longer controlled with this class of drugs, opioids should be started. A variety of opioids are available, and they differ widely with respect to analgesic potency and adverse effects among the elderly. Although the aged population requires lower doses of opioids, only careful titration based on individual response can ensure the appropriate response to clinical demand. Elderly patients are potentially more likely to be affected by opioid toxicity because of the physiological changes associated with aging. Nevertheless, appropriate dosage and administration may limit these risks. Cancer patients with pain who do not respond to increasing doses of opioids because they develop adverse effects before achieving acceptable analgesia may be switched to alternative opioids. Despite the favourable effects reported with opioid switching, monitoring is crucial, particularly in the elderly or patients who are switched from high doses of opioids. Adjuvant analgesics, including antidepressants, antiepileptics, corticosteroids and bisphosphonates may help in the treatment of certain types of chronic pain. With an appropriate and careful approach, it should be possible to reduce or eliminate unrelieved cancer pain in most elderly patients and, consequently, to enhance their quality of life. Older patients with cancer should be continuously assessed for cancer pain, both before and after analgesic treatment. PMID- 17727306 TI - Bleeding during enoxaparin treatment more common with age over 75 years and severe renal insufficiency. AB - BACKGROUND: Severe renal insufficiency, defined as a creatinine clearance <30 mL/min, increases the risk for bleeding in elderly patients receiving enoxaparin (enoxaparin sodium) treatment. METHODS: The risk/benefit ratios of enoxaparin and unfractionated heparin (UFH) in patients with acute myocardial infarction (AMI) aged >75 years were determined by investigating the parameters of efficacy (ischaemic event, lethal outcome), safety (bleeding events, renal insufficiency) or both (composite endpoint: ischaemic event or lethal outcome or bleeding event). RESULTS: The study included 113 patients (59 male, 52.2%) with AMI aged >75 years; 36 of these patients received enoxaparin. In the patients who had severe renal insufficiency, bleeding events were more frequent in those receiving enoxaparin than in those patients who received UFH (3 vs 1, respectively; p = 0.024). Irrespective of the presence of renal insufficiency, bleeding events occurred more often in patients who received enoxaparin than in those who received UFH (13 vs 8, respectively; p = 0.007). The composite endpoint showed a nonsignificantly better profile in patients who received enoxaparin than in those who received UFH. CONCLUSION: Although the use of enoxaparin (compared with UFH) and the presence of severe renal insufficiency significantly increased the occurrence of bleeding in patients with AMI aged >75 years, the risk/benefit difference in this population was not significant. PMID- 17727307 TI - Determining therapeutic approaches in the elderly with rectal cancer. AB - BACKGROUND: To evaluate the toxicity and feasibility of pelvic radiotherapy (RT) and/or surgery in elderly patients with locally advanced low-lying rectal cancer. PATIENTS AND METHODS: From November 1999 to November 2005, 51 patients aged >or=70 years who underwent RT for locally advanced low-lying rectal cancer were retrospectively examined. Variables considered were age, co-morbidities (evaluated according to the Charlson score and the Cumulative Illness Rating Scale-Geriatric [CIRS-G] score) and surgery versus no surgery. RESULTS: The median age was 80 years (range 70-94 years) and the male : female ratio was 33 : 18. A total of 5.9% of patients were considered 'fit', 72.5% had one or more CIRS G grade 1 or 2 co-morbidities and 21.6% had one or more CIRS-G grade 3 co morbidities. 54.9% of patients underwent surgery and 45.1% underwent RT. Only 9 of 21 (42.8%) patients who underwent radical resection received the full course of adjuvant RT and only seven (50%) of all patients treated with RT alone received the full dose of therapy. Patients with one or more CIRS-G grade 3 co morbidities reported similar numbers of grade 1-2 toxicities as patients with one or more CIRS-G grade 2 co-morbidities. CONCLUSION: Notwithstanding the small number of patients analysed, the findings of this study indicate that elderly patients with rectal cancer and mild co-morbidities could probably receive the same treatment as fit elderly patients, given that tolerability appeared to be similar in both categories of patients. Neither age nor co-morbidities should be considered reasons to deny the patient the possible benefits of receiving complete treatment. Moreover, Multidimensional Geriatric Assessment should always be undertaken to help clinicians make better decisions about treatment. Further prospective trials are needed to confirm these results. PMID- 17727308 TI - Mother-child double incompatibility at vWA and D5S818 loci in paternity testing. AB - BACKGROUND: In a paternity dispute case, 17 autosomal short tandem repeats (STR) were examined and signified a possible paternal mismatch at vWA locus and a maternal mismatch at D5S818 locus in the child under investigation. METHODS: Seventeen autosomal, 17 Y-chromosome and six X-chromosome repeat loci were used in parentage analysis. The mutated vWA and D5S818 alleles were amplified, cloned and sequenced to analyze the repeat structure. RESULTS: The vWA locus genotype in the mother, questioned child and suspected father were 18/19, 16/18 and 14/18, and were 13/15, 11/12 and 11/14, respectively, for the D5S818 locus. A complete match with the mother at six X-chromosome STR loci and with the father at 17 Y chromosome STR loci was observed. Nucleotide sequence analysis of the family at vWA alleles indicated the maternal loss of the repeat motif TCTA by two repeat units and a loss of AGAT repeat by one unit in the D5S818 locus leading to an allele mismatch in the child. The probability of maternity and paternity were 0.999999 and 0.999999, respectively. CONCLUSIONS: This is the first study of a maternally transmitted microsatellite mutation in the loci D5S818 and vWA in paternity DNA testing. The results convincingly established that the mother and suspected father are the biological parents of the questioned child. PMID- 17727309 TI - Matrix metalloprotease-2 and -9 concentration and activity in serum and culture medium samples: a methodological reappraisal. AB - BACKGROUND: Matrix metalloproteases (MMPs) play an important role in cardiovascular remodeling by degrading the extracellular matrix. The aim of this study was to compare two different methods for MMP-2 and MMP-9 concentration and activity determination. METHODS: MMP-2 and -9 levels were measured by immunometric and enzymatic assays to determine total and active levels. The two procedures differ in assay principle and in the extent of cross-reactions with interfering substances present in biological samples. Both human serum and culture medium from an ex vivo human model of intimal hyperplasia were checked. RESULTS: All methods were able to detect MMP-2 and -9 with similar levels of sensitivity, reproducibility and accuracy, and furnished positively related results, although significantly different, in both types of sample. Both systems were able to detect changes in MMP production such as the time-course of MMP-2 and -9 release by cultured saphenous vein associated with intima hyperplasia progression. CONCLUSIONS: Our data indicate that different values for MMP concentrations can be obtained using different analytical methods, even if they are intrinsically reliable. This suggests that methodological differences should be taken into account when comparing MMP results from different studies. PMID- 17727310 TI - Angiotensin-converting enzyme (ACE) I/D corrected serum ACE activity and severity assessment of community-acquired pneumonia. AB - BACKGROUND: Various studies have described decreased serum angiotensin-converting enzyme (ACE) activity in patients with pneumonia. The aim of the present study was to evaluate the role of ACE in pneumonia by comparing ACE insertion/deletion (I/D) genotype corrected serum ACE activity and to establish whether the severity of the disease correlates with lower ACE activity. METHODS: This was a prospective hospital-based observational study including 134 patients with pneumonia. Serum ACE activity was determined at admission, on days 2, 3, 5 and 10 of hospital stay, and at recovery. Based on ACE genotype and reference values, corresponding Z-scores were calculated. Disease severity, quantified by the acute physiology score (APS), and clinical outcome were compared between tertile groups of the Z-scores. RESULTS: A significant decrease in serum ACE activity during an episode of pneumonia with return to control range during recovery was observed for all three genotypes (II, ID and DD). The calculated Z-scores showed a negative correlation with APS scores (p=0.050). No significant association between decreased serum ACE activity and clinical outcome was observed. CONCLUSIONS: Serum ACE activity is significantly decreased during the acute phase of pneumonia. Despite correction for ACE I/D genotype, decreased ACE activity did not show a prognostic value. Further studies are needed to examine the mechanisms behind and diagnostic value of decreased ACE activity in community-acquired pneumonia. PMID- 17727311 TI - The effect of endurance exercise-induced lactacidosis on biochemical markers of bone turnover. AB - BACKGROUND: Stress fractures are frequent injuries among athletes. In vitro, decreases in pH stimulate osteoclasts and inhibit osteoblasts. We hypothesized that exercise-induced lactacidosis stimulates osteoclasts and reduces osteoblast activity in vivo. METHODS: A total of 32 volunteers (MA, male athletes; MCo, male controls; female athletes; and female controls) performed three 60-min cycle ergometer tests at 75%, 95% and 110% of their individual anaerobic threshold (IAT). Blood was taken before and at 3 and 24 h after exercise. Osteocalcin (OC), pro-collagen type I N-terminal peptide (PINP), C-terminal telopeptides of collagen I (CTx) and tartrate-resistant acid phosphatase (TRAP) were measured. RESULTS: At 75% and 95% IAT, pH did not change. At 110% IAT, pH decreased in MA by 0.08 units (p=0.041) and in MCo by 0.03 units (p=0.017). The pH results were substantiated by circulating lactate concentrations. The bone resorption markers TRAP and CTx were not consistently modified by any of the exercise tests. Exercise at 75% decreased OC and PINP in all groups. Exercise at 95% and 110% did not induce homogeneous effects. CONCLUSIONS: Anaerobic exercise does not systemically affect bone turnover, suggesting that exercise-induced acidosis is not involved in the pathogenesis of stress fractures. PMID- 17727312 TI - Preservation of RNA for functional analysis of separated alleles in yeast: comparison of snap-frozen and RNALater solid tissue storage methods. AB - BACKGROUND: The aim of the present study was to compare RNALater with the usual method of liquid nitrogen snap freezing as a surrogate mRNA preservation method for functional analysis of separated alleles in yeast (FASAY). METHODS: A total of 81 patients with transitional cell carcinoma of the bladder underwent fresh tissue biopsies directly transferred into RNALater and stored at room temperature or at 4 degrees C for increasing time intervals until RNA processing. From this cohort of patients, 53 paired snap-frozen and RNALater preservative-suspended tissues were obtained. Samples immediately frozen in liquid nitrogen were further stored at -80 degrees C. RESULTS: Of the 81 RNALater samples, 14 were not processed for FASAY because of RNA degradation. Of the remaining 67 samples, 15 (22%) were FASAY-positive. Identical FASAY results were found for 50 of 53 (94.4%) paired samples and the percentage of red yeast colonies was highly correlated (Cohen's kappa<0.82; p<0.00001). A single p53 missense mutation was found in each of the three discordant positive FASAY and was identical in each concordant positive sample (10/53). Storing samples in RNALater at room temperature for 3 days and at 4 degrees C for less than 1 month provided high quality mRNA suitable for FASAY. CONCLUSIONS: Our results demonstrate that RNALater is a suitable and flexible alternative to snap freezing for FASAY analysis. PMID- 17727313 TI - Clinical significance of the laboratory determination of low serum copper in adults. AB - BACKGROUND: Low serum copper is often indicative of copper deficiency. Acquired copper deficiency can cause hematological/neurological manifestations. Wilson disease (copper toxicity) is associated with neurological manifestations and low serum copper, with copper deposited in tissues responsible for the toxicity. Low serum copper can also be observed in some carriers of the Wilson disease gene and aceruloplasminemia. This study was undertaken to determine the clinical significance of low serum copper. METHODS: The Mayo Medical Laboratories', Metals Laboratory database was reviewed over a 9-month period to identify patients who received their care at the Mayo Clinic and had low serum copper. The medical records were analyzed to determine the significance of the low copper. RESULTS: In six of the 57 patients with low serum copper, the low copper was due to Wilson disease. In the remaining 51 patients, copper deficiency due to an underlying cause was identified in 38 as a reason for the low serum copper. The most commonly identified neurological manifestation of copper deficiency was myeloneuropathy. Coexisting nutrient deficiencies and hematological manifestations of copper deficiency were often but not invariably present. CONCLUSIONS: Copper deficiency, Wilson disease (or a carrier state), and aceruloplasminemia are all associated with low serum copper. The presence of coexisting neurological or hematological manifestations that are recognized sequelae of copper deficiency should be considered prior to making a diagnosis of copper deficiency. Gastrointestinal disease or surgery is a common cause of acquired copper deficiency. Even in patients in whom low serum copper is indicative of copper deficiency, the cause of the copper-deficient state may not be evident. PMID- 17727304 TI - A composite screening tool for medication reviews of outpatients: general issues with specific examples. AB - Regular performance of medication reviews is prominent among methods that have been advocated to reduce the extent and seriousness of drug-related problems, such as adverse drug reactions, drug-disease interactions, drug-drug interactions, drug ineffectiveness and cost ineffectiveness. Several screening tools have been developed to guide practising healthcare professionals and researchers in reviewing the medication patterns of elderly patients; however, each of these tools has its own limitations. This review discusses a wide range of general prescription-, treatment- and patient-related issues that should be taken into account when reviewing medication patterns by implicit screening. These include generic and therapeutic substitution; potentially superfluous or inappropriate medications; potentially inappropriate dosages or duration of treatment; drug-disease and drug-drug interactions; under-treatment; making use of laboratory test results; patient adherence, experiences and habits; appropriate dosage forms and packaging. A broad selection of specific examples and references that can be used as a basis for explicit screening of medication patterns in outpatients is also offered. PMID- 17727314 TI - Calculated low-density lipoprotein cholesterol remains a viable and important test for screening and targeting therapy. AB - BACKGROUND: Most clinical laboratories use calculated (C) low-density lipoprotein cholesterol (LDL-C) for measurement. Some studies have questioned the linearity of CLDL-C in the clinically useful low range. Moreover, it is generally believed that calculation leads to poor precision such that variation in CLDL-C is greater than the 4% guideline since the calculation is dependent on three primary variables. Actually, the degree of variability of a calculated value will be small if the variability of each primary value is small as compared to its contribution to the calculated value. When LDL-C is low, high-density lipoprotein cholesterol (HDL-C), that has poorer precision, becomes more important in defining the precision of CLDL-C. New homogeneous (direct) HDL-C (dHDL) methods show better precision than the older heterogeneous methods. We hypothesized that a direct homogeneous HDL-C method would substantially improve the low range precision of LDL-C as compared to older heterogeneous HDL-C methods. METHODS: We compared CLDL-C to a standardized electrophoretic method that shows very high precision. We also compared the precision of CLDL-C calculated using a homogeneous dHDL and a heterogeneous indirect method. RESULTS: We found good linearity for CLDL-C down to 500 mg/L (x0.002586). The main source of CLDL-C variation was HDL-C. Precision was within guidelines when the dHDL method was used. Using our automated methods for lipoprotein lipids, assuming our reference method is accurate, the formula that calculated CLDL-C (mg/dL) using triglyceride (mg/dL) (x0.001129) x0.2 suggested by some gave more accurate results than the formula using triglyceride (mg/dL) x0.16 suggested by others. CONCLUSIONS: Given the potential for CLDL-C to meet the precision guidelines, until direct LDL-C methods can be refined, CLDL-C should continue to be the primary test used for assessing LDL-C clinically. Standardized testing for CLDL-C for manufacturers should be available so that the formula used for each instrument can provide well defined accuracy. PMID- 17727315 TI - The soluble transferrin receptor reflects tumor load in chronic lymphocytic leukemia. AB - BACKGROUND: The soluble transferrin receptor (sTfR) is a parameter of erythropoietic activity and iron deficiency. Increased levels have also been described in hematological malignancies, especially in chronic lymphocytic leukemia (CLL). METHODS: We investigated the value of sTfR in the assessment of tumor mass in 61 previously untreated CLL patients. Both hemolysis and iron deficiency were excluded. sTfR was measured nephelometrically (normal 0.81-1.75 mg/L). RESULTS: All Binet A patients had normal sTfR values (1.36+/-0.22 mg/L). In Binet B patients, the sTfR was increased (3.08+/-1.70 mg/L, p<0.0001) compared to Binet A patients. Binet B patients with normal sTfR had a small tumor load and no abdominal involvement. A further increase of sTfR in Binet C (3.75+/- 2.32 mg/L) was not significant compared to Binet B patients. sTfR values decreased or even normalized after successful treatment, whereas relapse or disease progression was associated with another increase of sTfR. CONCLUSIONS: The sTfR concentration directly reflects the tumor burden in CLL. Therefore, sTfR may be of clinical value in monitoring disease activity, response to treatment and disease progression. PMID- 17727316 TI - Association of classical and related inflammatory markers with high-sensitivity C reactive protein in healthy individuals: results from the Stanislas cohort. AB - BACKGROUND: Although high-sensitivity C-reactive protein (hs-CRP) has emerged as a cardiovascular marker, questions arise regarding the relative information provided by other inflammatory molecules. Therefore, as a first step, we examined interrelationships between serum hs-CRP concentrations and inflammatory, adhesion and growth factors in healthy adults. METHODS: Circulating concentrations of hs CRP, haptoglobin, orosomucoid, interleukin-6 (IL-6), IL-8, IL-18, tumor necrosis factor-alpha (TNF-alpha), TNF-receptor II (TNF-RII), E-, P-, and L-selectins, intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1, endothelial growth factor (EGF), vascular EGF (VEGF), insulin-like growth factor 1 (IGF-1) and IGF-binding protein (IGFBP-3) were measured in 154 men and 161 women of the Stanislas cohort. Leukocyte and platelet counts were also determined. RESULTS: Correlations were significant between hs-CRP concentrations and leukocyte and platelet counts, as well as haptoglobin, orosomucoid, IL-6, and ICAM-1 concentrations (p< or =0.001). Correlation coefficients for ICAM-1 were higher in men than in women (p< or =0.05). When stratifying subjects according to hs-CRP levels, the group with high hs-CRP levels had significantly higher haptoglobin and orosomucoid concentrations than the others, in addition to higher leukocyte counts and IL-6 concentrations in women, and platelet counts and ICAM-1 concentrations in men. CONCLUSIONS: Further studies are warranted to explain the association pattern for hs-CRP. Partition of these factors according to their association with hs-CRP concentration opens a new perspective for choice of the best factors in terms of cardiovascular risk in relation to hs-CRP, while non associated markers could be used to give additional information. PMID- 17727317 TI - Are changes in blood-ethanol concentration during storage analytically significant? Importance of method imprecision. AB - BACKGROUND: Knowledge about the stability of drugs and metabolites in biological fluids is important information when the analytical results are evaluated and interpreted. This study examines changes in blood-ethanol concentration (BEC) during the storage of specimens for up to 12 months at 4 degrees C. METHODS: Venous blood samples were taken from drunk drivers in evacuated glass tubes containing sodium fluoride and potassium oxalate as chemical preservatives. The concentrations of ethanol in blood were determined in duplicate by headspace gas chromatography on arrival at the laboratory and again after storage in a refrigerator at 4 degrees C for up to 12 months. RESULTS: The relationship between the standard deviation (SD) of analysis of ethanol at concentration intervals of 0.2 mg/g (BEC) was defined by the linear regression equation SD=0.00243+0.0104 BEC (r=0.99). At a mean BEC of 1.64 mg/g, the SD was 0.019 mg/g which corresponds to a coefficient of variation of 1.1%. The mean decrease in BEC (+/-SD) between first and second analysis was 0.105+/- 0.0686 mg/g (t=19.3, d.f.=158, p<0.001) and the loss of alcohol was positively correlated with the duration (days) of storage (r=0.44, p<0.001), although with large inter-tube variations. A correlation also existed (r=0.23, p<0.01) between the loss of ethanol and the starting BEC. When blood samples (n=49) were opened 17 times to remove aliquots for analysis over 6.5 months, the BEC decreased by 0.217+/-0.054 mg/g compared to a fall of 0.101+/-0.076 mg/g in tubes kept unopened. None of the blood samples showed a significant increase in BEC after storage. CONCLUSIONS: To be considered analytically significant, the BEC had to decrease by 0.013 (2.6%), 0.028 (1.9%) and 0.045 mg/g (1.8%), respectively at starting concentrations of 0.5, 1.5 and 2.5 mg/g. PMID- 17727319 TI - The therapeutic potential of targeting anti-Ribosomal-P antibody in treating SLE patients with depression. AB - Neuropsychiatric systemic lupus erythematosus (NPSLE) involves the central and peripheral nervous system. The pathogenesis of NPSLE is poorly understood. The condition is recognised as one of the major causes of mortality in SLE patients. The main autoantibody population associated with NPSLE is directed to ribosomal phosphoproteins (anti-Ribos.P), which can bind the limbic area of mouse brain and penetrate into neuronal cells in vitro. Intracerebroventricular injection of these antibodies, induce experimental depression-like models in naive mice. Based on these observations, targeting anti-Ribos.P antibodies may be a new therapeutic approach to treat NPSLE patients with depression. PMID- 17727318 TI - High plasma levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) and interleukin-8 (IL-8) characterize patients prone to ventricular fibrillation complicating myocardial infarction. AB - BACKGROUND: Atherosclerotic plaques prone to cause thrombotic complications and plaque rupture account for the majority of fatal myocardial infarctions (MI), which may be complicated by ventricular fibrillation (VF). Matrix-degrading metalloproteinases (MMPs) and their inhibitors (TIMPs) are expressed in atherosclerotic lesions and contribute to plaque vulnerability. Interleukin-8 (IL 8) is one of the predominant chemokines interacting with MMPs and TIMPs and the coagulation system. The aim of the present study was to assess potential differences of levels of MMP-9, TIMP-1 and IL-8 in postmyocardial infarction patients with or without VF complicating acute MI. METHODS: Blood samples were taken from 45 patients with VF complicating acute MI and from 88 patients without VF. All samples were collected during a symptom-free interval remote from the acute ischemic event with a median of 556 days. The markers of interest were TIMP 1, MMP-9 and IL-8. RESULTS: IL-8 and TIMP-1 levels were significantly higher among patients with VF than among patients without VF (p<0.001). In a logistic regression approach IL-8 was an independent indicator of patients prone to VF during MI (p=0.03). High levels of TIMP-1 (p=0.05), MMP-9 (p=0.03), the MMP 9/TIMP-1 ratio (p=0.049) and hypertension (p=0.02) were found to be indicators in patients with reinfarction or unstable angina pectoris during follow-up. Hypertension (p=0.02) and MMP-9 (p=0.03) were the only significant indicators characterizing patients undergoing coronary reinterventions, such as percutaneous coronary interventions and coronary bypass surgery. CONCLUSIONS: Higher TIMP-1 and IL-8 levels are present in patients with VF complicating MI. High TIMP-levels may be related to the degree of fibrosis which is a substrate for electrical instability and may contribute to the occurrence of VF. Patients prone to develop VF during MI seem to have an increased proinflammatory condition compared to patients without VF. PMID- 17727320 TI - B-cell targeting: a novel approach to immune intervention today and tomorrow. AB - B cells and their products, antibodies, play an important role in the diagnosis and, in some instances, in the pathogenesis of many autoimmune diseases. Specific B-cell directed therapies are of recent interest as their impact on B-cell activity can influence a variety of autoimmune diseases. The development and introduction of rituximab, a depleting antibody targeting CD20+ B cells, and previously CD52-directed treatment with Campath-1h for the treatment of B-cell malignancies as well as rheumatoid arthritis have pioneered this therapeutic field. Other non-depleting strategies employ CD22 or B-cell activating factor/B lymphocyte stimulator and apoptosis-inducing ligand as targets and are under clinical investigation at present. Abnormalities of B-cell subsets have been identified by a number of independent groups which often represent characteristic patterns of disturbances of the human B-cell repertoire. However, the clinical value of specific B-cell subset targeting/depletion has not been addressed extensively. As such an approach may afford the possibility to avoid unnecessary adverse events related to depletion of non-pathogenic B-cell populations, B-cell subset targeting may have the capacity to enhance the benefit/risk ratio of B cell immune intervention. PMID- 17727321 TI - Regulatory T cells and immunity to pathogens. AB - Immune responses to pathogens are modulated by one or more types of cells that perform a regulatory function. Some cells with this function, such as CD4+ Foxp3+ natural regulatory T cells (nTreg), pre-exist prior to infections whereas others may be induced as a consequence of infection (adaptive Treg). With pathogens that have a complex pathogenesis, multiple types of regulatory cells could influence the outcome. One major property of Treg is to help minimize collateral tissue damage that can occur during immune reactions to a chronic infection. The consequence is less damage to the host but in such situations the pathogen is likely to establish persistence. In some cases, a fine balance is established between Treg responses, effector components of immunity and the pathogen. Treg responses to pathogens may also act to hamper the efficacy of immune control. This review discusses these issues as well as the likely mechanisms by which various pathogens can signal the participation of Treg during infection. PMID- 17727322 TI - The potential of cord blood stem cells for use in regenerative medicine. AB - It is estimated that up to 128 million individuals might benefit from regenerative medicine therapy, or almost 1 in 3 individuals in the US. If accurate, the need to relieve suffering and reduce healthcare costs is an enormous motivator to rapidly bring stem cell therapies to the clinic. Unfortunately, embryonic stem (ES) cell therapies are limited at present by ethical and political constraints and, most importantly, by significant biologic hurdles. Thus, for the foreseeable future, the march of regenerative medicine to the clinic will depend on the development of non-ES cell therapies. At present, non-ES cells easily available in large numbers can be found in the bone marrow, adipose tissue and umbilical cord blood (CB). Each of these stem cells is being used to treat a variety of diseases. This review shows that CB contains multiple populations of pluripotent stem cells, and can be considered the best alternative to ES cells. CB stem cells are capable of giving rise to hematopoietic, epithelial, endothelial and neural tissues both in vitro and in vivo. Thus, CB stem cells are amenable to treat a wide variety of diseases including cardiovascular, ophthalmic, orthopedic, neurologic and endocrine diseases. PMID- 17727323 TI - CD8 T cells and latent herpes simplex virus type 1: keeping the peace in sensory ganglia. AB - Herpes simplex virus type 1 (HSV-1) infections represent a significant worldwide heath problem. The lack of an effective therapy to curtail reactivation of HSV-1 from a state of neuronal latency has lead to significant morbidity and mortality. Effective therapies to prevent reactivation must likely elicit a protective CD8 T cell response that could act to prevent reactivation from sensory neurons prior to release of infectious virus at the periphery. This review focuses on the present understanding of how CD8 T cells maintain HSV-1 latency and how this knowledge could facilitate the generation of more effective therapeutic modalities. PMID- 17727325 TI - Gene therapy of gynaecological diseases. AB - Gene therapy represents a potentially useful approach for the treatment of diseases refractory to conventional therapies. Various preclinical and clinical strategies have been explored for treatment of gynaecological diseases. Given the most severe unmet clinical need, much of the work has been performed with gynaecological cancers and ovarian cancer in particular. Although the safety of many treatment strategies has been demonstrated in early phase clinical trials, efficacy has been mostly limited heretofore. Major challenges include improving the vectors used with the aim of more effective and selective delivery. In addition, effective penetration into and spreading within advanced and complex tumour masses and metastases remains challenging. This review focuses on existing and developmental gene transfer applications for gynaecological diseases. PMID- 17727326 TI - MicroRNA expression in lymphoma. AB - MicroRNAs are a recently discovered class of short (approximately 22 nucleotide) naturally occurring RNA molecules that negatively regulate gene expression post transcriptionally. There has been an explosion of interest in the microRNA field as these molecules have been found to play key roles in a wide range of biological processes and to be aberrantly expressed in many types of cancer, including haematological malignancies. Cancer-associated microRNAs can act as both tumour suppressor molecules (e.g., miR-15a and miR-16-1) and have oncogenic properties (e.g., miR-155 and miR-17-92 cluster). In this review the authors discuss the rapidly accumulating evidence for the central role that microRNAs play in both haematopoiesis and haematological malignancy, in particular focusing on their role in lymphoma. PMID- 17727327 TI - miRNA genetic alterations in human cancers. AB - MicroRNAs (miRNAs) are endogenous, non-coding, small RNAs, which negatively regulate gene expression in a sequence-specific manner via translational repression and/or mRNA degradation. Their discovery revealed a new and exciting aspect of post-transcriptional gene regulation that is universally involved in cellular homeostasis. Importantly, the advent of miRNAs added another level of complication in the already complex regulatory networks of the cell, undermining that RNA molecules in general, should be considered gene regulators of equal importance with proteins. Recently, the scientific community drew attention to the miRNA field for an additional reason: an increasing line of evidence indicated that miRNA genes are tightly connected with the process of tumorigenesis. Indeed, several miRNAs have already been demonstrated to behave as oncogenes or tumor suppressor genes in many types of cancer. Even though the underlying mechanisms by which miRNAs can destabilize the normal cellular processes, promoting cell transformation and tumor progression, are not well understood, genetic and epigenetic alterations most probably play a critical role. Significant technologic advances facilitated the profiling of the miRNA expression patterns in normal and cancer tissues and discovered an unexpected greater reliability of miRNA expression signatures in classifying cancer types than the respective signatures of protein-coding genes. Along with this extraordinary diagnostic potential, miRNAs have also proved their prognostic value in predicting clinical behaviors of cancer patients. The aim of this review is to describe miRNA expression and how its deregulation is involved in the pathophysiology of human cancers. PMID- 17727324 TI - Gene therapy for mucopolysaccharidosis. AB - Mucopolysaccharidoses (MPS) are due to deficiencies in activities of lysosomal enzymes that degrade glycosaminoglycans. Some attempts at gene therapy for MPS in animal models have involved intravenous injection of vectors derived from an adeno-associated virus (AAV), adenovirus, retrovirus or a plasmid, which primarily results in expression in liver and secretion of the relevant enzyme into blood. Most vectors can correct disease in liver and spleen, although correction in other organs including the brain requires high enzyme activity in the blood. Alternative approaches are to transduce hematopoietic stem cells, or to inject a vector locally into difficult-to-reach sites such as the brain. Gene therapy holds great promise for providing a long-lasting therapeutic effect for MPS if safety issues can be resolved. PMID- 17727328 TI - The micro RNA target paradigm: a fundamental and polymorphic control layer of cellular expression. AB - Evidence is emerging that micro RNA (miRNA) is an important and potentially polymorphic regulatory layer for silencing gene expression in vivo. Knowledge of miRNA targeting may help to elucidate the function of many human genes in common diseases, providing a powerful target validation technology. Accurate in silico prediction of miRNA targets in mRNA is a critical capability, allowing effective evaluation of the impact of variation on the creation, strengthening, weakening and destruction of miRNA binding sites. Application of such analyses identifies thousands of single-nucleotide polymorphisms, which may potentially impact miRNA regulation of mRNA. The authors believe this information may offer a real opportunity to study miRNA function at a number of levels. First, sequence focused analysis will help to define the functional boundaries of miRNA target binding. Second, one may be able to identify miRNA target variants in mRNA with a direct role in human disease, which may be valuable therapeutic targets. PMID- 17727329 TI - Antibody therapeutics: isotype and glycoform selection. AB - Recombinant monoclonal antibody (rMAb) therapy may be instituted to achieve one of two broad outcomes: i) killing of cells or organisms (e.g., cancer cells, bacteria); and ii) neutralisation of soluble molecules (e.g., cytokines in chronic disease or toxins in infection). The choice of rMAb isotype is a critical decision in the development of a therapeutic antibody as it will determine the biological activities triggered in vivo. It is not possible, however, to accurately predict the in vivo activity because multiple parameters impact on the functional outcome, for example, IgG subclass, IgG-Fc glycoform, epitope density, cellular Fc receptors polymorphisms and so on. The present understanding of the molecular interactions between IgG-Fc and effector ligands in vitro has allowed the generation of new antibody structures with altered/improved effector function profiles that may prove optimal for given disease indications. Thus, when maximal antibody-dependent cell-mediated cytotoxicity activity is indicated a non fucosylated IgG1 format may be optimal; when minimal activity is indicated an aglycosylated IgG2 may be the form of choice. PMID- 17727330 TI - Myxoma virus and oncolytic virotherapy: a new biologic weapon in the war against cancer. AB - Oncolytic virotherapy is an innovative alternative to more conventional cancer therapies. The ability of some viruses to specifically target and kill malignant cancerous cells while leaving normal tissue unscathed has opened a large repertoire of new and selective cancer killing therapeutic candidates. Poxviruses, such as vaccinia virus, have a long history of use in humans as live vaccines and have more recently been studied as potential platforms for delivery of immunotherapeutics and attenuated variants of vaccinia have been explored as oncolytic candidates. In contrast, the poxvirus myxoma virus is a novel oncolytic candidate that has no history of use in humans directly, as it has a distinct and absolute host species tropism to lagomorphs (rabbits). Myxoma virus has been recently shown to be able to also selectively infect and kill human tumor cells, a unique tropism that is linked to dysregulated intracellular signalling pathways found in the majority of human cancers. This review outlines the existing knowledge on the tropism of myxoma virus for human cancer cells, as well as preclinical data exhibiting its ability to infect and clear tumors in animal models of cancer. This is an exciting new therapeutic option for treating cancer, and myxoma virus joins a growing group of oncolytic virus candidates that are being developed as a new class of cancer therapies in man. PMID- 17727331 TI - PEGylated bioactive molecules in biodegradable polymer microparticles. AB - Injectable peptide and oligonucleotide biotherapeutics offer great promise for treatment of serious chronic diseases but almost always need further formulation work to increase stability and circulation lifetimes. Covalent attachment of poly(ethylene glycol) (PEG) will increase circulation lifetimes up to a week or so and decrease degradation in favorable cases. Encapsulation in biodegradable polymer microparticles has been highly successful, mostly for peptides to provide sustained release up to several months after injection. Although products are on the market using these technologies, PEGylation and microparticle encapsulation each have drawbacks that prevent more widespread use. When they are combined, the limitations of one technology may be resolved by the other. Work in several laboratories on encapsulation of PEGylated bioactive molecules has revealed a synergy. Activity reduction and restricted circulation lifetimes for PEGylated bioactive agents is addressed by microencapsulation and using a lower PEG molecular weight. Chemical degradation, excessive burst release and limited drug content are typical problems for microparticles that are ameliorated by using PEGylated actives. The case for synergy between PEGylation and microencapsulation is illustrated in this review by work with several proteins and peptides including insulin, and the oligonucleotide therapeutic, pegaptanib. PMID- 17727332 TI - Role of pulmonary adenosine during hypoxia: extracellular generation, signaling and metabolism by surface adenosine deaminase/CD26. AB - Numerous parallels exist between limited oxygen availability (hypoxia) and acute inflammation. The lungs in particular are prone to acute inflammation during hypoxia, resulting in pulmonary edema, vascular leakage and neutrophil infiltration. The innate response elicited by hypoxia is associated with increased extracellular adenosine effects. Although studies on acute pulmonary hypoxia show a protective role of extracellular adenosine by attenuating pulmonary edema and excessive inflammation, chronic elevation of pulmonary adenosine may be detrimental. Adenosine deaminase (ADA)-deficient mice, for example, develop signs of chronic pulmonary injury in association with highly elevated levels of adenosine. Thus, the authors hypothesized the existence of hypoxia-elicited clearance mechanisms to offset deleterious influences of chronically elevated adenosine. Such studies indicated a second response to hypoxia characterized by pulmonary induction of ADA and CD26. In fact, hypoxia inducible ADA is enzymatically active and tethered on the outside of the membrane via CD26 to form a complex capable of degrading extracellular adenosine to inosine. This paper reviews metabolic and transcriptional changes of extracellular adenosine generation, signaling and degradation during acute and prolonged pulmonary hypoxia. PMID- 17727333 TI - The role of cathelicidin and defensins in pulmonary inflammatory diseases. AB - Antimicrobial peptides (AMPs) protect the epithelia of mucosal organs like the respiratory or the gastrointestinal tract from invading microorganisms. As an integral part of the innate immune system they display antimicrobial activity against gram- and gram-negative bacteria as well as against fungi and enveloped and non-enveloped viruses. Besides their microbicidal effects they have important functions in the regulation of repair and inflammation. AMPs are sometimes referred to as 'alarmins' due to their ability to recruit, modulate and activate components of the immune system. In contrast, some AMPs suppress activation of the immune system. AMPs are also involved in tissue repair, cancer biology and angiogenesis. Based on their antimicrobial and immunomodulatoy functions, AMPs are probably involved in the pathogenesis of infectious and inflammatory diseases of the lung. Inborn or acquired deficiencies contribute to susceptibility to infection and colonisation. The potential pro-inflammatory role of AMPs contributes to the disease processes in inflammatory disorders such as asthma, chronic obstructive pulmonary disease, sepsis or pulmonary fibrosis. This review summarises the knowledge about the functions of AMPs in the pulmonary innate host defence system and their role in respiratory disease. PMID- 17727334 TI - 5T4-modified vaccinia ankara: progress in tumor-associated antigen-based immunotherapy. AB - Both the expression and biology of the tumor-associated antigen (TAA) 5T4 suggest that it is an effective target for cancer immunotherapy. This paper reviews the development of a novel immunotherapeutic vaccine comprising the highly attenuated modified vaccinia ankara virus encoding 5T4 (MVA-5T4, aka TroVax). Preclinical studies have demonstrated that MVA-5T4 is safe and highly effective in both the prophylactic and active treatment of syngeneic murine tumor models. More importantly, > 700 doses of MVA-5T4 have been administered to > 200 patients to date. Reported results from clinical trials in metastatic colorectal, metastatic renal and hormone-refractory prostate cancer patients demonstrate that MVA-5T4 is safe and highly immunogenic, both as a monotherapy and in combination with standard-of-care therapies including irinotecan, oxaliplatin, IFN-alpha and IL-2. These studies demonstrate that MVA-5T4 induces potent and sustained immune responses in approximately 95% of tested patients. In addition, post-hoc analyses of these studies have noted a correlation between anti-5T4 immune responses and indicators of clinical benefit. With its minimal side effects and demonstrated ability to produce strong immune responses in patient populations, MVA-5T4 is a promising addition to the cancer therapy arsenal. PMID- 17727335 TI - Palivizumab and the prevention of respiratory syncytial virus illness in pediatric patients with congenital heart disease. AB - Respiratory syncytial virus (RSV) is a significant pathogen for infants and children with congenital heart disease. Non-sustained immunity and failure to develop an effective vaccine has steered RSV management toward a passive immunotherapy strategy in at-risk children. Palivizumab is a humanized murine monoclonal antibody targeting the RSV envelope F glycoprotein. In a Phase III clinical trial palivizumab significantly reduced RSV hospitalization in children with significant congenital heart disease and was proven to be safe. Palivizumab is one of the first monoclonal antibodies to significantly impact a pediatric disease. PMID- 17727336 TI - The effects of local bFGF release and uniaxial strain on cellular adaptation and gene expression in a 3D environment: implications for ligament tissue engineering. AB - The objectives of this investigation were (1) to characterize the growth factor release profile of a basic fibroblast growth factor (bFGF)-coated three dimensional (3D) polymer scaffold under static and cyclically strained conditions, and (2) to delineate the individual and collective contributions of locally released bFGF and mechanical strain on cellular morphology and gene expression in this 3D system. Scaffolds were treated with I(125)-bFGF and subjected to mechanical strain or maintained in a static environment and the media sampled for factor release over a period of 6 days. Over the first 10 hours, a burst release of 25% of the incorporated growth factor into the surrounding media was noted. At 24 hours, approximately 40% of the bFGF was released into the media, after which steady state was achieved and minimal subsequent release was noted. Mechanical stimulation had no effect on growth factor release from the scaffold in this system. To test the concerted effects of bFGF and mechanical stimulation on bone marrow stromal cells (BMSCs), scaffolds were loaded with 0, 100, or 500 ng of bFGF, seeded with cells, and subjected to mechanical strain or maintained in a static environment. Scaffolds were harvested at 1, 7, and 21 days for RT-PCR and histomorphometry. All scaffolds subjected to growth factor and/or mechanical stimulation demonstrated cellular adherence and spreading at 21 days. Conversely, in the absence of both bFGF and mechanical stimulation, cells demonstrated minimal cytoplasmic spread. Moreover, at 21 days, cells subjected to both mechanical stimulation and bFGF (500 ng) demonstrated the highest upregulation of stress-resistive (collagen I, III) and stress-responsive proteins (tenascin-C). The effect of growth factor may be dose sensitive, however, as unstrained scaffolds treated with 100 ng of bFGF demonstrated upregulation of gene expression comparable to strained scaffolds treated with lower doses of bFGF (0 or 100 ng). In conclusion, results from this study suggest that the stimulatory effects of bFGF are dose sensitive and appear to be influenced by the addition of mechanical strain. The concurrent application of biochemical and mechanical stimuli may be important in promoting the adaptation of BMSCs and driving the transcription of genes essential for synthesis of a functional ligament replacement tissue. PMID- 17727337 TI - ECM molecules mediate both Schwann cell proliferation and activation to enhance neurite outgrowth. AB - Tissue engineering using a combination of biomaterials and cells represents a new approach to nerve repair. We have investigated the effect that extracellular matrix (ECM) molecules have on Schwann cell (SC) attachment and proliferation on the nerve conduit material poly-3-hydroxybutyrate (PHB), and SC influence on neurite outgrowth in vitro. Initial SC attachment to PHB mats was unaffected by ECM molecules but proliferation increased (laminin > fibronectin > collagen). SCs seeded onto ECM-coated culture inserts suspended above a monolayer of NG108-15 cells determined the effect of released diffusible factors. The effect of direct contact between the two cell types on ECM molecules was also investigated. In both systems SCs enhanced neurite number per cell and percentage of NG108-15 cells sprouting neurites. NG108-15 cells grown in direct contact with SCs had significantly longer neurites than those exposed to diffusible factors when seeded on laminin or fibronectin. Diffusible factors released from SCs cultured on ECM molecules appear to initiate neurite outgrowth, whereas SC-neuron contact promotes neurite elongation. SC proliferation was maximal on poly-D-lysine-coated surfaces, but these cells did not influence neurite outgrowth to the levels of laminin or fibronectin. This suggests that ECM molecules enhance cell number and activate SCs to release neurite promoting factors. Addition of ECM molecules to PHB nerve conduits containing SCs is likely to provide benefits for the treatment of nerve injuries. PMID- 17727338 TI - Fine-needle aspiration molecular analysis for the diagnosis of papillary thyroid carcinoma through BRAF V600E mutation and RET/PTC rearrangement. AB - OBJECTIVE: To evaluate BRAF(V600E) mutation on consecutive fine-needle aspiration biopsy (FNAB) specimens in order to assess FNAB's usefulness in preoperative papillary thyroid carcinoma (PTC) diagnosis with the contemporaneous analysis of RET/PTC1 and RET/PTC3 rearrangements obtained from ex vivo thyroid nodules. DESIGN: Thyroid FNABs from 156 subjects with nodules and 49 corresponding surgical samples were examined for the presence of BRAF mutation by real-time allele-specific polymerase chain reaction, confirmed with the use of a laser pressure catapulting system. Samples were also examined for RET/PTC rearrangements. The results were compared with the cytological diagnosis and histopathology. MAIN OUTCOMES: 13/156 cytological examinations were diagnostic for PTC and 19/156 showed suspicious/indeterminate FNAB (12.2%). FNAB-BRAF(V600E) mutation was detected in 11/16 (69%) cases with histological confirmation of PTC. In our series, RET/PTC rearrangement was detected in only one case of PTC, whereas it was not present in any case of adenoma, goiter, or Hashimoto's thyroiditis. No PTC case was found positive at the same time for BRAF mutation and RET/PTC rearrangements. CONCLUSION: BRAF(V600E) mutation detected on FNAB specimens, more than RET/PTC rearrangements, is highly specific for PTC and its routine research might well be an adjunctive and integrative diagnostic tool for the preoperative diagnostic iter. PMID- 17727339 TI - New insights into thyroid stem cells. AB - Stem cells exhibit an extraordinary ability for self-renewal. They also give rise to many specialized cells. The potential of stem cells in regenerative medicine, developmental biology, and drug discovery has been well documented. Although advances in stem cell science have raised broad ethical concerns, it is clear that stem cell technology has revolutionized our thinking in modern biology and medicine and provided the basis for understanding many of the mechanisms controlling basic biological processes and disease mechanisms. This review details the nascent field of thyroid stem cell research, exploring the current status of thyroid stem cell differentiation from the perspectives of both developmental biology and cell replacement therapy. It highlights successes to date in the generation of thyroid follicular cells from embryonic stem cells in the laboratory and the identification and characterization of adult stem cells from human thyroid glands and thyroid cancers. Finally, it outlines future challenges with a focus on potential stem cell therapy for thyroid patients. PMID- 17727340 TI - Clinical practice guidelines for communicating prognosis and end-of-life issues with adults in the advanced stages of a life-limiting illness, and their caregivers. PMID- 17727342 TI - Don't ignore the passing train... thoughts on being pro-active. PMID- 17727341 TI - Structures of the four subfamilies of phosphodiesterase-4 provide insight into the selectivity of their inhibitors. AB - PDE4 (phosphodiesterase-4)-selective inhibitors have attracted much attention as potential therapeutics for the treatment of both depression and major inflammatory diseases, but their practical application has been compromised by side effects. A possible cause for the side effects is that current PDE4 selective inhibitors similarly inhibit isoforms from all four PDE4 subfamilies. The development of PDE4 subfamily-selective inhibitors has been hampered by a lack of structural information. In the present study, we rectify this by providing the crystal structures of the catalytic domains of PDE4A, PDE4B and PDE4D in complex with the PDE4 inhibitor NVP {4-[8-(3-nitrophenyl) [1,7]naphthyridin-6-yl]benzoic acid} as well as the unliganded PDE4C structure. NVP binds in the same conformation to the deep cAMP substrate pocket and interacts with the same residues in each instance. However, detailed structural comparison reveals significant conformational differences. Although the active sites of PDE4B and PDE4D are mostly comparable, PDE4A shows significant displacements of the residues next to the invariant glutamine residue that is critical for substrate and inhibitor binding. PDE4C appears to be more distal from other PDE4 subfamilies, with certain key residues being disordered. Our analyses provide the first structural basis for the development of PDE4 subfamily selective inhibitors. PMID- 17727344 TI - Gender identity disorders: diagnostic and surgical aspects. AB - Transsexualism is defined as a strong and persistent cross-gender identification with the patient's persistent discomfort with his or her sex and a sense of inappropriateness in the gender role of that sex (Diagnostic and Statistical Manual of Mental Disorders, fourth revision, text revision [DSM-IV-TR]). The disturbance is not concurrent with a physical intersex condition and causes clinical distress or impairment in social, occupational, or other important areas of functioning. The trained mental health professional is obliged to find out if the patient fulfills the criteria of an irreversible gender transposition and if he or she will benefit from medical (hormonal and surgical) sex-reassignment treatment. If a patient has absolved 12 months of real-life experience and at least 6 months of continuous hormonal treatment, the indication for surgical sex reassignment may be given. Genital sex-reassignment in male-to-female transsexuals includes vaginoplasty, preferably by inversion of penoscrotal skin flaps, clitoroplasty, and vulvoplasty. The operation may be performed in one or two sessions. In contrast to genital reassignment in male-to-female patients, no operative standards are available in female-to-male subjects. Recently, neophallus creation from sensate free forearm flaps has emerged as the most promising approach for those patients who want to have a neophallus. Other alternatives such as metoidoioplasty or neophallus reconstruction from regional flaps exist, but are also accompanied by multiple possible complications and re interventions. Best results are to be expected when using multidisciplinary teams of plastic surgeons, urologists, gynecologists, and experts in sexual medicine in large volume centers. PMID- 17727345 TI - The use of collagenase in the treatment of Peyronie's disease M.K. Gelbard, A. Lindner, and J.J. Kaufman. PMID- 17727346 TI - Penoscopy: optical corporotomy and resection for prosthesis implantation in cases of penile fibrosis, Shaeer's technique. PMID- 17727348 TI - Congressional campaign launched to promote post-prostate cancer treatment equity. PMID- 17727347 TI - Are the Endocrine Society's Clinical Practice Guidelines on Androgen Therapy in Women misguided? A commentary. AB - The Endocrine Society Clinical Guidelines on Androgen Therapy in Women (henceforth referred to as the Guidelines) do not necessarily represent the opinion held by the many health-care professionals and clinicians who are specialized in the evaluation, diagnosis, and treatment of women's health in androgen insufficiency states. The recommendations provided in the published Guidelines are neither accurate nor complete. We disagree with the therapeutic nihilism promoted by these Guidelines. The members of the Guidelines Panel (henceforth referred to as the Panel), in their own disclaimer, stated that the Guidelines do not establish a standard of care. Based on data available in the contemporary literature, on the role of androgens in women's health, we provide in this commentary a point-by-point discussion of the arguments made by the Panel in arriving at their recommendations. It is our view that the Guidelines are not based on the preponderance of scientific evidence. Health-care professionals, physicians, and scientists often disagree when determining how best to address and manage new and emerging clinical issues. This is where we stand now as we endeavor to understand the role of androgens in a woman's health and welfare. Indeed, some basic facts are not in contention. All agree that dehydroepiandrosterone sulfate (DHEA-S) production from the adrenal gland begins during the preteen years, peaks in the mid 20s, then declines progressively over time. In contrast, ovarian androgen (i.e., testosterone) secretion commences at puberty, is sustained during a woman's peak reproductive years and declines as a woman ages, with a more rapid and steep decrease after surgical menopause. However, there are ample data to suggest that adrenal androgens play a role in the development of axillary and pubic hair, and that testosterone is critical for women's libido and sexual function. We take this opportunity to invite members of the Panel on Androgen Therapy in Women to discuss, clarify, comment, or rebut any of the points made in this Commentary. It is our goal to elevate this debate in order to provide women who are afflicted with androgen insufficiency and sexual disorders with the highest quality health care and to relieve their distress and suffering, as well as to improve their quality of life. PMID- 17727349 TI - Sex after seventy: a pilot study of sexual function in older persons. AB - INTRODUCTION: Limited information is available regarding sexual functioning among adults aged 70 years and older. AIMS: To assess sexual functioning among older men and women, and ascertain patient-physician communication patterns about sexual functioning. METHODS: Prospective participants were approached prior to scheduled appointments with their primary care physician. In-depth sexual histories were obtained along with data on their demographic, medical, psychological, and cognitive status. MAIN OUTCOME MEASURES: Sexual functioning was assessed using standardized questionnaires, and simple yes/no questions were administered to ascertain information regarding patient-physician communication practices about sex. RESULTS: Of the 74 eligible patients approached, 50 (68%) participated. The participants had a mean age +/- standard deviation (SD) of 81 +/- 6 years and most (56%) were women. Eighteen percent of the women and 41% of the men were sexually active. The most commonly reported sexual activity was intercourse for men and masturbation for women. Among the women, the most commonly cited reason for being sexually inactive was "no desire," whereas for most men, it was "erectile dysfunction." Sexual function scores for women were low across each category (lubrication, desire, orgasm, arousal, pain, and satisfaction.) For men, low sexual function scores were found in the domains of erectile function, orgasm, and overall satisfaction, but not desire. Only 4% of the women (vs. 36% of men) reported initiating a discussion about sexual function with their physician in the past year, whereas 7% of the women (vs. 32% of men) reported that their physician inquired about the topic in the preceding year. Finally, 32% of the women (vs. 86% of men) felt that physicians should initiate discussions about sexual function. CONCLUSION: In this study of older adults, a minority reported current sexual activity. Among sexually inactive women, most did not wish to resume activity, whereas desire for sexual activity remained high among men, despite substantial problems with erectile dysfunction. PMID- 17727350 TI - Functional and morphological improvement in erectile tissue of hypertensive rats by long-term combined therapy with phosphodiesterase type 5 inhibitor and losartan. AB - INTRODUCTION: Erectile dysfunction (ED) is highly associated to cardiovascular disease, especially arterial hypertension. Phosphodiesterase type 5 (PDE5) inhibitors and angiotensin II receptor blockers (ARB) are both common and efficient therapy in patients with ED and arterial hypertension, respectively. AIM: To evaluate the effect of PDE5 inhibitor, sildenafil (S), and of ARB Losartan (L) in a continuous combined therapy for a long term on penile structures in a hypertensive rat model. METHODS: During 6 months, four groups of male spontaneously hypertensive rats (SHR) and one of Wistar-Kyoto (WKY) rats, as control group, were studied: no-treatment SHR, SHR with L, SHR with S, SHR with S + L, and no-treatment WKY. Cavernous smooth muscle (CSM) and vascular smooth muscle (VSM) from cavernous arteries, collagen type III (COL-III), and endothelial nitric oxide synthase (eNOS) expression in cavernous space were evaluated. MAIN OUTCOME MEASURE: Functional and morphological differences between S and L in a continuous combined therapy vs. either drug as monotherapy on penile structures. RESULTS: After 6 months, SHR that received L, S, or combined therapy showed a similar reduction in blood pressure compared with untreated SHR. Nevertheless, SHR + L + S and control WKY showed significantly lower values of (i) CSM (P < 0.01), (ii) VSM (P < 0.01), and (iii) COL-III (P < 0.01) when compared with the untreated SHR and also with the SHR with monotherapy. Additionally, SHR + L + S, presented a higher eNOS expression in sinusoidal endothelium in comparison with the untreated SHR and the SHR with monotherapy (P < 0.01). In vitro studies revealed that SHR + L + S displayed a better relaxation response to acetylcholine than the untreated SHR and the SHR with monotherapy (P < 0.01). CONCLUSION: These results suggest that a long-term combined therapy using L and S is a useful tool for functional and structural modification in cavernous tissue from SHR. PMID- 17727351 TI - Sexual function and satisfaction in adults based on the definition of child sexual abuse. AB - INTRODUCTION: The literature shows a discrepancy in the association between child sexual abuse (CSA) and adult sexual function. One of the proposed explanations for this discrepancy is the different ways in which CSA is assessed. While some studies explicitly ask potential participants whether they are sexual abuse survivors, others ask whether participants experienced specific unwanted sexual behaviors. AIM: This study investigated the differences between women who self identified as CSA survivors, women who experienced similar unwanted sexual experiences but did not identify as CSA survivors (NSA), and women with no history of sexual abuse (control). CSA was defined as unwanted touching or penetration of the genitals before the age of 16. METHODS: A sample of 699 college students anonymously completed a battery of questionnaires on sexuality and sexual abuse history. MAIN OUTCOME MEASURES: Sexual function was measured with the Female Sexual Function Index (FSFI), and sexual satisfaction was measured with the Sexual Satisfaction Scale-Women. History of CSA was measured with a modified version of Carlin and Ward's childhood abuse items. RESULTS: Differences emerged between women who experienced sexual abuse before age 16 and women who never experienced sexual abuse (control) on the personal distress subscale of the Sexual Satisfaction Scale. The CSA group (N = 89) reported greater sexual distress compared to the NSA (N = 98) group, and the NSA group reported more distress than the control group (N = 512). No significant group differences were observed in the FSFI. Characteristics of the abuse that predicted whether women identified as CSA survivors included vaginal penetration, fear at the time of the abuse, familial relationship with the perpetrator, and chronic frequency of the abuse. These abuse characteristics were associated with sexual satisfaction but not with sexual function. CONCLUSIONS: Differences in levels of sexual satisfaction between women with and without a history of CSA were associated with the type of CSA definition adopted. It remains unexplained why the CSA group showed more personal distress about their sexuality but not more sexual dysfunction. PMID- 17727352 TI - Methods to determine the minimum important difference for a sexual event diary used by postmenopausal women with hypoactive sexual desire disorder. AB - INTRODUCTION: Recently, there has been much discussion in the literature about how to determine the meaningfulness of results generated from a patient-reported outcome measure. A number of reviews have shown that there are two main approaches: anchor- and distribution-based approaches for determining the minimum important difference (MID) for a new measure. There are issues with calculating an MID using each method: Will the two approaches give the same estimate? If the estimates differ, how do you decide on one estimate? Would asking patients directly be more beneficial? AIM: A case study was presented to address these issues based on a newly developed diary assessing number of satisfactory sexual events (SSEs) per week in women with hypoactive sexual desire disorder (HSDD). METHODS: Anchor- and distribution-based estimates were generated from data gathered in two double-blind, placebo-controlled, parallel group trials for the treatment of HSDD (N = 788). A novel interview study was used to ask women directly about an MID for SSEs (N = 77). MAIN OUTCOME MEASURES: Defining the MID for an SSE diary in women with HSDD. RESULTS: The estimates varied, producing a range of mean MID estimates between 0.04 and 0.46 SSEs per week. CONCLUSION: We recommend that rather than defining the MID, a range should be selected from the set of estimates formed by the limits of the 95% confidence intervals. PMID- 17727354 TI - The Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision as an appropriate diagnostic for premature ejaculation. AB - INTRODUCTION: The Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR) criteria for premature ejaculation (PE) are multifactorial, and include concepts of latency, perceived control over ejaculation, and personal distress and interpersonal difficulty related to the condition. Recent publications have suggested that these criteria are not supported by empirical evidence, leading to the proposal that a PE diagnosis should be based solely on intravaginal ejaculatory latency time (IELT), while the presence of other factors (such as perceived lack of control over ejaculation) may be used to guide treatment decisions. AIM: To examine the evidence supporting the elements of the DSM-IV-TR criteria for PE. MAIN OUTCOME MEASURES: Literature searches on IELT, perceived control over ejaculation, and personal distress and interpersonal difficulty related to ejaculation. RESULTS: From a historical perspective, there has been a lack of large observational studies that evaluated the contributions of the DSM-IV-TR components in men with PE. However, recently performed large observational studies have generated data supporting the inclusion of perceived control over ejaculation and personal distress related to ejaculation in the definition of PE. Furthermore, emerging evidence indicates that a perceived lack of control over ejaculation is directly associated with elevated personal distress related to ejaculation and decreased satisfaction with sexual intercourse, while the effects of IELT on these parameters are indirect, and mediated by perceived control over ejaculation. A key advantage of the DSM-IV TR approach to the diagnosis of PE is that it firmly links PE to a negative outcome for the patient, which is an element common to diagnostic criteria for other conditions, including depression, hypertension, and osteoporosis. CONCLUSIONS: This new evidence strongly suggests that the DSM-IV-TR criteria for PE encompass aspects of the condition that patients describe as important. PMID- 17727353 TI - Chronic lead exposure may be associated with erectile dysfunction. AB - INTRODUCTION: Heavy metals constitute significant potential threats to human health in both occupational and environmental settings. Research examining the etiology of lead toxicity-induced hypertension reveals that the free radical production and lowering of inherent antioxidant reserves resulting from lead toxicity are directly related to vasoconstriction underlying lead-induced hypertension. A similar mechanism would affect smooth muscle relaxation in the cavernous tissue leading to erectile dysfunction (ED). AIM: Is to study the possible hazardous effect of chronic lead exposure on the erectile function, and to document the deposition of lead in the cavernous tissue. METHODS: The study group consisted of 34 men with ED, consecutively scheduled for penile implant insertion at Cairo University Hospital, as well as 15 controls. We determined the blood lead level for the two groups by the use of atomic absorption spectrophotometry. Sixteen of the 34 patients, and none of the 15 controls, had elevated lead serum levels (above 25 [g/dL]). MAIN OUTCOME MEASURES: We estimated the levels of two reactive oxygen species (ROS) and four antioxidants in peripheral blood for the two groups. At the time of penile implant insertion, we prepared cavernous tissue paraffin sections stained with Mallory-Parker stain to study lead deposition. We also prepared ultrathin sections for electron microscopy. We estimated cavernous tissue lead level. RESULTS: The ED group had significantly higher blood lead level when compared with the control group. A significant positive correlation was found between the blood lead level and cavernous tissue lead level of the ED group. Individuals with high blood lead had significantly higher levels of serum ROS and significantly lower levels of serum antioxidants, compared with those having low blood lead. Histological sections from patients with high blood lead showed deposition of grayish lead granules in the cavernous tissue. CONCLUSIONS: Chronic lead exposure may be associated with ED. PMID- 17727355 TI - Concomitant ventral phalloplasty during penile implant surgery: a novel procedure that optimizes patient satisfaction and their perception of phallic length after penile implant surgery. AB - INTRODUCTION: Despite previous reports showing consistently elevated patient satisfaction with penile implantation, it is our impression that patients who have had a prosthesis placed often complain of penile shortening postoperatively. AIM: We sought to evaluate if the release of the penoscrotal web would optimize patient perception and satisfaction regarding penile length after such procedure. MAIN OUTCOME MEASURE: Utilizing a questionnaire, we evaluated patient satisfaction, focusing on phallic size. METHODS: Ninety patients (mean age 62) underwent penile prosthesis placement during a 17-month period. Forty-three were carried out with takedown of penoscrotal web during a 17-month period (group 1). Of group 1, 39 patients had an inflatable implant placed (inflatable penile prosthesis) and 4 had a semirigid implant. The patients were directly inquired with a seven-item questionnaire 3 months after the procedure. These results were then compared to a group of 37 patients that had penile implants placed without release of the penoscrotal web (group 2). All the patients involved in the study had a high insertion of the scrotum ventrally (penoscrotal web). RESULTS: Of the patients, 42/43 (98%) (group 1) reported good overall satisfaction of the surgical procedure; 36/43 (84%) reported some degree of increase in penile length; 5/43 (12%) reported no significant change in their perception of penile length postoperatively. The remaining two patients reported a decreased penile length. The clinical records from group 2 demonstrated 31/37 (84%) of the patients complained of penile shortening, and only one patient reported an increase in penile length. Postoperative complications in group 1 consisted of wound hematoma (2/43) and focal superficial wound dehiscence (3/43). The operative time for group 1 patients was approximately 12 minutes (mean 11.7) longer. CONCLUSIONS: Release of penoscrotal web is a simple, safe, and reproducible procedure that can enhance patient perception of penile length and further improve satisfaction. PMID- 17727356 TI - Koro--the psychological disappearance of the penis. AB - The aim of this article is to present a summarizing overview on ethnomedical aspects of koro (in Chinese called suo-yang), the panic anxiety state in which affected males believe that the penis is shrinking and/or retracting, and perhaps disappearing. While reduction of penile volume occurs physiologically due to vasoconstriction in cold temperature and intense anxiety, it is believed in certain cultures that genital shrinking leads to impotence and sterility, and eventually to death. Traditional Chinese medicine treats suo-yang, the reduction of the male principle yang, as a dangerous disturbance of the life-sustaining yin yang equilibrium of the organism. Koro has therefore been held to be a Chinese "culture-bound" condition. However , the koro phenomenon is also known among diverse ethnic and religious groups in Asia and Africa, typically in cultures in which reproductive ability is a major determinant of a young person's worth. Koro epidemics of panic anxiety due to widespread fears of losing one's genitals, procreative ability, and even one's life, are triggered by rumors of genital disappearance supposedly caused in China by female fox spirits, in Singapore and Thailand by mass poisoning, and in Africa by sorcery, usually in the context of socioeconomic or political tension. Today, in contemporary Western societies, ideas of genital disappearance are not culturally endorsed. But historically, it should be remembered that in the late Middle Ages in Europe, a man could lose his membrum virile through magical attacks by witches. The conclusion is that the psychological disappearance of the penis is a universal syndrome that was described recently in Asia and Africa and already in Medieval Europe. PMID- 17727357 TI - The forgotten foreskin and its ridged band. PMID- 17727359 TI - 5-HT1A receptors on oxytocin neurons and premature ejaculation--a comment. PMID- 17727362 TI - Angiogenesis in skin aging and photoaging. AB - Angiogenesis, the process of generating new blood vessels, is affected by various physiological and pathological conditions of skin. The skin aging process can be divided into intrinsic aging and photoaging. With aging, cutaneous blood vessels undergo pronounced alterations. A reduction of the cutaneous microvasculature has been observed in the skin of elderly individuals. Human skin is exposed daily to solar ultraviolet (UV) radiation, infrared rays and heat, and these stimuli are known to induce skin angiogenesis. Interestingly, although acute UV irradiation stimulates skin angiogenesis, cutaneous blood vessels are decreased in chronically photodamaged skin. The reason for the differential effects of acute and chronic UV exposure on skin angiogenesis remains to be elucidated. This review discusses the vascularization changes in intrinsically aged and photoaged human skin, the effects of UV irradiation, infrared rays and heat on skin angiogenesis, and the effects of topical retinoic acid treatment on UV-induced angiogenesis and cutaneous vascularity in aged and photoaged human skin. An understanding of the molecular mechanisms of aging- and photoaging-dependent changes of skin angiogenesis may provide us with new insights to prevent and treat the skin aging process. PMID- 17727363 TI - Autoinflammatory syndromes with a dermatological perspective. AB - The term autoinflammatory syndromes describes a distinct group of systemic inflammatory diseases apparently different from infectious, autoimmune, allergic and immunodeficient ones. Originally, it was almost synonymous with clinically defined hereditary periodic fever syndromes, including familial Mediterranean fever, hyper immunoglobulin D syndrome with periodic fever and tumor necrosis factor receptor-associated periodic syndrome. Similar but distinct periodic fever syndromes accompanied by urticarial rash, familial cold autoinflammatory syndrome, Muckle-Wells syndrome and chronic infantile neurological cutaneous articular syndrome, have all been reportedly associated with CIAS1 mutations and are collectively called cryopyrin-associated periodic syndromes. Consequently, the concept of autoinflammatory syndromes has been spread to contain other systemic inflammatory diseases: rare hereditary diseases with or without periodic fevers, such as pyogenic sterile arthritis, pyoderma gangrenosum and acne syndrome, Blau syndrome and chronic recurrent multifocal osteomyelitis, and the more common collagen disease-like diseases, such as Behcet's disease, Crohn's disease, sarcoidosis and psoriatic arthritis. These diseases are all caused by or associated with mutations of genes regulating innate immunity and have common clinical features accompanied with activation of neutrophils and/or monocytes/macrophages. In this review, major autoinflammatory syndromes are summarized and the pathophysiology of related skin disorders is discussed in association with dysregulated innate immune signaling. PMID- 17727364 TI - Molecular analysis of Malassezia microflora in the lesional skin of psoriasis patients. AB - Systemic and focal infections by microorganisms have been known to induce or exacerbate psoriasis. To investigate the role of Malassezia species in the development of psoriasis, we analyzed the Malassezia microflora in psoriasis patients using a nested polymerase chain reaction (PCR) assay, and compared it with those in atopic dermatitis (AD) patients and healthy subjects. Fungal DNA was directly collected from the lesional and non-lesional skin of the trunk of 22 psoriasis patients by applying a transparent dressing. The extracted DNA was amplified by using specific primers designed for the PCR in the intergenic spacer or internal transcribed spacer area of the ribosomal RNA. All nine of the Malassezia species were detected at different rates from the 22 psoriasis patients. The overall detection rates in lesional and non-lesional skin of M. restricta, M. globosa and M. sympodialis were high (96%, 82% and 64%, respectively), whereas the detection rates of the other species were relatively low. However, there was no difference in the rates between lesional and non lesional skin areas. The average number of Malassezia species detected in overall sites of the psoriasis patients was 3.7 +/- 1.6 species, although this fact showed no correlation with the severity of the symptoms. The number of Malassezia species detected was 4.1 +/- 1.9 in the AD patients, and 2.8 +/- 0.8 in the healthy subjects, suggesting that the skin microflora of psoriasis patients and AD patients show greater diversity than that of healthy subjects. PMID- 17727365 TI - Simultaneous effect of ursolic acid and oleanolic acid on epidermal permeability barrier function and epidermal keratinocyte differentiation via peroxisome proliferator-activated receptor-alpha. AB - Ursolic acid (UA) and oleanolic acid (ONA) are pentacyclic triterpenoids, which naturally occur in many medicinal herbs and plants. Recent research revealed that several pharmacological effects could be attributed to UA and ONA, such as anti tumor, anti-inflammatory and anti-microbial activities. To evaluate the effects of UA and ONA on epidermal permeability barrier recovery and normal skin, both flanks of hairless mice were topically treated with either 0.01-0.1 mg/mL UA or 0.1-1.0 mg/mL ONA after tape stripping and transepidermal water loss (TEWL) were assessed, and then hydration and TEWL were measured for 3 weeks with application of UA and ONA (2 mg/mL). We also investigated the morphological changes using light (LM) and electron microscopic (EM) examination. Finally, we observed that UA and ONA stimulated epidermal keratinocyte differentiation via peroxisome proliferator-activated receptor (PPAR)-alpha using Western immunoblotting. The recovery rate of epidermal permeability barrier after tape stripping increased in the UA- and ONA-treated groups (0.1 mg/mL UA and 0.5 mg/mL ONA) at 6 h to more than 20% when compared to the vehicle-treated group (P < 0.05). In both groups, hydration was increased compared to the vehicle group from 1 week without TEWL alteration (P < 0.05). An LM finding showed that epidermal thickening was frequently observed (UA > ONA > vehicle). EM examination revealed an increase in secretion and in the number of lamellar bodies in treated groups and that complete formation of lipid bilayers was also prominent (ONA > UA > vehicle). Protein expression of PPAR-alpha, involucrin, loricrin and filaggrin increased twofold and threefold in HaCaT cells treated for 24 h with either ONA (10 micromol/L) or UA (10 micromol/L), respectively, reflecting that the UA and ONA can improve the recovery of skin barrier function and induce epidermal keratinocyte differentiation via PPAR-alpha. Taken together, these results suggest that UA and ONA will be pertinent candidates for the improvement of epidermal permeability barrier function. PMID- 17727366 TI - Dry dermoscopy in clinical treatment of alopecia areata. AB - Although dermoscopy is conventionally utilized with immersion gel for diagnosis of pigmented tumor, we utilized dry dermoscopy, which is dermoscopy without immersion gel, for clinical treatment of alopecia areata (AA). The scalp skin and hair of a 38-year-old Japanese male, and 23-, 22- and 47-year-old Japanese females with AA, whose normal hair color was black, were examined by dry dermoscopy. Exclamation mark hairs, short hairs, fractured hairs and black dots, all characteristic of AA, were detected by dry dermoscopy of the scalp of the 23 year-old female with ophiasis type AA. In the case of the 47-year-old female with round hair loss on the occipital scalp and diffuse hair loss over the fronto vertical region, dry dermoscopy was useful for diagnosis of AA based on hair characteristic of AA. After she received corticosteroid pulse therapy with 500 mg of i.v. methylprednisolone on 3 successive days, her hair showed apparent regrowth and disappearance of the abnormal hairs characteristic of AA, evidenced by dry dermoscopy 1 month later. In a case of long-lasting AA in the 23-year-old female, we found a follicular plaque-like appearance at the opened hair follicle pores by dry dermoscopy. Histopathologically, the incompletely differentiated remnant hair shaft was packed in the follicular infundibulum. In addition, regrowing vellus hairs, which were difficult to clinically recognize, were detected by dry dermoscopy. Dry dermoscopy is therefore useful for both diagnosis and follow up of AA. PMID- 17727367 TI - Characteristics of acquired reactive perforating collagenosis. AB - The status of the patient's associated disease can generally affect the onset or healing of acquired reactive perforating collagenosis (ARPC). We treated eight cases of ARPC and noted that the patients had similar findings. However, it was not clear why ARPC developed in the patients with these diseases. Nevertheless, several factors related to the diseases associated with ARPC could affect the degeneration of collagen fibers or the production of dermal products. Some patients had diseases that were characterized by fibrosis and an increased amount of reticular fibers. Factors related to tissue remodeling might act not only in diseases associated with ARPC but also in ARPC itself. PMID- 17727368 TI - Paraneoplastic pemphigus presenting as erythrodermic lichenoid dermatitis with concomitant features of pemphigus foliaceus. AB - We describe a patient with paraneoplastic pemphigus who presented with erythrodermic lichenoid dermatitis, later developing blisters of pemphigus foliaceus type and oral erosive lesions. In addition to antibodies against the plakin family proteins, the patient's serum was positive for anti-desmoglein 1 antibodies without coexisting anti-desmoglein 3 activities by enzyme-linked immunosorbent assay, which is a very rare autoantibody profile in paraneoplastic pemphigus. PMID- 17727369 TI - Childhood bullous pemphigoid treated by i.v. immunoglobulin. AB - Bullous pemphigoid is an acquired autoimmune subepidermal blistering disorder mostly seen in the elderly. Childhood bullous pemphigoid is very rare. For the first time we report a case of childhood bullous pemphigoid associated with infantile eczema. Two weeks after a routine vaccination, a 3.5-month-old boy with infantile eczema developed a generalized blistering disorder. Histopathology revealed a subepidermal blister. Direct immunofluorescence showed linear depositions of C3 along the basement membrane zone. Indirect immunofluorescence studies demonstrated the presence of circulating immunoglobulin G antibodies directed against the epidermal side of salt-split skin. Enzyme-linked immunosorbent assay demonstrated serum level of anti-BP180 antibody elevated. The patient was successfully treated by high-dose i.v. immunoglobulin. PMID- 17727370 TI - Case of subcutaneous sparganosis: use of imaging in definitive preoperative diagnosis. AB - Herein, we report a rare case of subcutaneous sparganosis in a 60-year-old Japanese woman. She had a 2 cm x 2 cm elastic-hard, subcutaneous nodule, which was the larva of a tapeworm, and a surrounding granuloma in her internal thigh. It was thought that she became infected by drinking water contaminated with the worm. She was definitively diagnosed by enzyme-linked immunosorbent assay (ELISA). After excision of the lesion, the titer of ELISA showed clear decline; therefore, we could conclude that she had been completely freed from sparganosis. The magnetic resonance imaging (MRI) and ultrasound sonography of her subcutaneous nodule demonstrated the characteristic signs: a band-like structure in the MRI and a coiled linear hypoechoic body in a clear, oval mass in the ultrasound sonography. PMID- 17727371 TI - Juvenile systemic sclerosis: report of three cases and review of Japanese published work. AB - Juvenile or childhood onset systemic sclerosis (SSc) is rare. In our department, we encountered three juvenile SSc patients among the overall 206 SSc patients. All three cases were diffuse cutaneous type SSc (dSSc) with positive antinuclear antibodies. In this report, we report the three patients and analyze clinical and serological features of 58 Japanese patients with juvenile SSc. Forty-eight patients (92.3%) were classified as dSSc and 21 out of 35 patients (60%) had anti topoisomelase I antibodies, while anticentromere antibodies were not detected in any patients. Prevalence of lung fibrosis and scleroderma renal crisis was low, however, the rate of cardiac involvement was higher than that in adult patients. PMID- 17727372 TI - Cutaneous metastasis as the first clinical manifestation of pancreatic adenocarcinoma: a case treated with gemcitabine. PMID- 17727373 TI - Segmental multiple cutaneous piloleiomyoma with an overlying epidermal proliferation. PMID- 17727375 TI - Merkel cell carcinoma combined with squamous cell carcinoma. PMID- 17727374 TI - Case of AIDS disclosed by refractory pruritic xerosis and molluscum contagiosum. PMID- 17727376 TI - Case of Werner's syndrome with pancreatic carcinoma. PMID- 17727378 TI - Familial acanthosis nigricans showing ichthyosiform skin lesions in two sisters. PMID- 17727377 TI - Acquired reactive perforating collagenosis triggered by insect bite. PMID- 17727379 TI - Current challenges in children with type 1 diabetes. PMID- 17727380 TI - Worldwide childhood type 1 diabetes incidence--what can we learn from epidemiology? AB - Type 1 diabetes is the most common form of diabetes in most part of the world, although reliable data are still unavailable in several countries. Wide variations exist between the incidence rates of different populations, incidence is lowest in China and Venezuela (0.1 per 100,000 per year) and highest in Finland and Sardinia (37 per 100,000 per year). In most populations girls and boys are equally affected. In general, the incidence increases with age, the incidence peak is at puberty. After the pubertal years, the incidence rate significantly drops in young women, but remains relatively high in young adult males up to the age 29-35 years. Prospective national and large international registries (DIAMOND and EURODIAB) demonstrated an increasing trend in incidence in most regions of the world over the last few decades and increases seem to be the highest in the youngest age group. Analytical epidemiological studies have identified environmental risk factors operating early in life which might have contributed to the increasing trend in incidence. These include enteroviral infections in pregnant women, older maternal age (39-42 years), preeclampsia, cesarean section delivery, increased birthweight, early introduction of cow's milk proteins and an increased rate of postnatal growth (weight and height). Optimal vitamin D supplementation during early life has been shown to be protective. Some of these environmental risk factors such as viruses may initiate autoimmunity toward the beta cell, other exposures may put on overload on the already affected beta cell and thus accelerate the disease process. PMID- 17727381 TI - Differential diagnosis of type 1 diabetes: which genetic syndromes need to be considered? AB - Recently it has become apparent that not all diabetes presenting in childhood is type 1. Increasingly type 2 diabetes, secondary diabetes, maturity onset diabetes of the young, and rare syndromic forms of diabetes such as Wolfram syndrome and Alstrom syndrome have been identified in children. Although individually rare, collectively they make up about 5% of children seen in diabetes clinics. The importance of these syndromes for children lies in the recognition of treatable complications, and for their parents, the possibility of genetic counselling. The scientific importance is enormous as they are experiments of nature that reveal basic mechanisms of insulin and glucose metabolism. We are now able to offer mutation analysis to correlate the clinical pattern to the genotype, and seek novel therapeutic approaches based on the developing knowledge of gene and protein functions. This review focuses on monogenic syndromes of diabetes, particularly where significant advances have been made in our understanding recently. Neonatal diabetes is a specialist field in its own right and is not included, except to discuss Kir6.2 diabetes which may develop in infancy. This review is written for the paediatric diabetes specialist and aims to provide information on the clinical features, natural history, genetics and management of children with diabetes as part of a syndrome. Finally there is information on useful investigations to aid diagnosis. PMID- 17727382 TI - Can we prevent diabetic ketoacidosis in children? AB - Diabetic ketoacidosis (DKA) is an acute potentially life-threatening complication of diabetes affecting more than 100,000 persons annually in the United States. Although major advances have improved diabetes care, DKA remains the leading cause of hospitalization, morbidity, and death in youth with type 1 diabetes (T1D). As the majority of patients presenting with DKA have established diabetes, it is important to address outpatient educational approaches directed at sick-day management and early identification and treatment of impending DKA. Teaching and reinforcement of sick-day rules involves improved self-care with consistent self monitoring of blood glucose and ketones, and timely administration of supplemental insulin and fluids. DKA as an initial manifestation of T1D may be less amendable to prevention except with an increased awareness by the lay and medical communities of the symptoms of diabetes and surveillance in high-risk populations potentially identified by family history or genetic susceptibility. New technologies that can detect the blood ketone 3beta-hydroxybutyrate (3beta OHB) instead of traditional urine ketones appears to provide opportunity for early identification and treatment of impending DKA leading to reduced need for hospitalization and potential cost-savings. PMID- 17727383 TI - Immune intervention at diagnosis--should we treat children to preserve beta-cell function? AB - Type 1 diabetes (T1D) is characterized by loss of beta-cell function. If beta cell function can be preserved, it will lead to improved metabolic balance with improved quality of life and fewer acute and late complications, and if residual insulin secretion improves well enough, then that could lead to complete remission and even cure of the disease. Several efforts to save residual beta cell function have been made for more than three decades without success. Proof of principle has been possible, and it seems clear that immune suppression or immune modulation, in fact, can stop the destructive process and thereby preserve beta-cell function. However, the effect seen in adult patients with T1D have been minimal or absent in diabetic children who seem to have another or at least more aggressive disease process. Furthermore, the immune interventions have had too serious and common adverse events in comparison to the scarce-positive effect. Recent more specific immune modulation with anti-CD3 monoclonal antibodies seems more encouraging with at least postponement of the C-peptide decline, but unfortunately still with common and quite threatening adverse effects. Even more promising are the autoantigen therapies, of which glutamic acid decarboxylase (GAD) vaccination has shown good results with impressive preservation of residual insulin secretion in 10- to 18-year-old type 1 diabetic patients with recent onset. In patients with short diabetes duration at intervention the effect was remarkable. Furthermore, these effects were achieved with no adverse events. Future studies will show whether the good effect seen so far can be confirmed. If so there is hope that GAD vaccination will cause remission and even cure and prevention of T1D will then no longer be just a dream. PMID- 17727384 TI - Identifying children at particular risk of long-term diabetes complications. AB - Formerly a 'taboo' subject, long-term complications are now being increasingly discussed with the family by the health-care team. Identifying potential predictors and establishing early intervention can change the course of these complications in the young patient with diabetes. Although the most recognized risk factor is glycaemic exposure, the development of diabetes complications is likely to result from an interaction between genetic and environmental factors. Other major environmental risk factors are hypertension, smoking, higher body mass index and lipid disorders. This article will concentrate on specific paediatric aspects, including the impact of puberty; endothelial dysfunction and genetic susceptibility. Endothelial function assessed by flow-mediated dilatation is a non-invasive method that has been suitable for use in children and adolescents. In type 1 diabetes mellitus children, endothelium dysfunction has been documented among patients with short diabetes duration and has been correlated to folate status, triglyceride and low-density lipoprotein cholesterol levels. Studies in the paediatric population have also revealed an association of diabetes complications with genetic variants in the renin-angiotensin system, polyol pathway, lipid oxidation and folate metabolism. Currently, achieving the best glycaemic control remains the gold standard for prevention of long-term diabetes complications in the clinical context. However, recent identification of genetic markers and development of research tools that predict long-term complications might have a potential role as instruments in assessing the effectiveness of intervention in the early course of the disease. PMID- 17727385 TI - Recent advances in insulin treatment of children. AB - Since the findings of the Diabetes Control and Complications Trial became public in 1993, intensive insulin therapy has been recommended for all children. However, successful implementation remains a challenge because of developmental, physiological and cultural, as well as practical issues specific to the pediatric population. This article reviews the different insulin regimens that are currently available, from the short- and intermediate-acting insulins to the newer insulin analogs, focusing on insulin therapies that attempt to provide a more physiologic basal-bolus approach to treatment. More and more children are on multiple daily injection regimens or using continuous subcutaneous insulin infusion to achieve better metabolic control. The achievement of optimal glycemic control in children is complicated by their variability in eating habits and activity levels and perhaps more importantly by the risk of hypoglycemia. The hope is that new technologies including continuous subcutaneous glucose monitoring and perhaps a closed-loop system in the near future will help us achieve more optimal glycemic targets in children without increased side effects. In addition, continuous glucose monitoring may teach us better ways to use insulin in children who do not have the technology available to them. PMID- 17727386 TI - The importance of carbohydrate counting in the treatment of children with diabetes. AB - Carbohydrate (Carb) counting is a meal planning approach for patients with diabetes mellitus that focuses on carbohydrate as the primary nutrient affecting postprandial glycemic response. The concept of carb counting is not new. In the early 1990's the Diabetes Control and Complications Trial (DCCT) used carb counting as one of its education tools. More recently, short acting insulin analogues and insulin pumps have made the role of carb counting important and popular. Carb counting can be used in conjunction with a meal plan to set carbohydrate targets at each meal and snack. It is also used, perhaps more commonly, to estimate carbohydrate intake and adjust insulin around mixed meals and snacks using insulin to carbohydrate ratio. This effectively addresses the variable eating habits of most children and adolescents. The method may be adapted for patients who use a conventional insulin regimen and may meet the needs of patients who use multiple daily injections (MDI) or an insulin pump. Carb counting can make food planning flexible and enjoyable for patients, and the meal planning approach is very important for the physical growth and psychological development of children with diabetes. This paper describes the importance of carb counting for childhood diabetes as well as some of the special aspects associated with it. PMID- 17727387 TI - Prerequisites for age-appropriate education in type 1 diabetes: a model programme for paediatric diabetes education in Germany. AB - Continuous diabetes education for children, adolescents and their parents are widely accepted as an integral part of every type 1 diabetes therapy. Especially in paediatric diabetes care age-appropriate, demand-oriented and individualized practical information and skills training are mandatory for achieving good metabolic control and psychosocial well-being. A paediatric multidisciplinary diabetes team experienced in an intensified insulin therapy with a differential substitution of prandial and basal insulin needs (MDI or CSII) and in child psychology is required to initiate and maintain lifelong diabetes self management. In Germany an education programme for children aged 6-12 years and another programme for adolescents and young adults have previously been evaluated in multicenter studies. Programmes were considered with respect to applicability, acceptance by target groups and efficacy (knowledge, competence, quality of life and glycaemic control). Furthermore, a programme specifically designed for parents of children affected was evaluated. Contents, modular structures, developmental psychological background and didactic concepts of all above mentioned programmes are presented in detail. Apart from teaching insulin therapy according to current guidelines special emphasis is laid on translating this knowledge into everyday self-management behaviour. In addition, emotional coping with the chronic disease and its psychosocial consequences is supported. In the context of the Disease-Management-Program for Type 1 Diabetes in Germany these programmes for young people were certified and reimbursed nationwide by health insurances. PMID- 17727389 TI - Can the analysis of GORD-related sleep disturbances help the clinician to better manage the disease? PMID- 17727388 TI - The role of new technologies in treating children and adolescents with type 1 diabetes mellitus. AB - Given the physiological and psychological impact of type 1 diabetes in children and adolescents, these patients present special challenges to pediatric health care providers. The goals of intensive management of diabetes have been clearly established since the publication of the Diabetes Control and Complication Trial (DCCT) in 1993, which demonstrated that tight metabolic control achieved with intensive insulin therapy is superior to conventional treatment in reducing the risk of long-term microvascular complications. Thus, current recommendations mandate that youth with type 1 diabetes should aim to achieve metabolic control as close to normal as possible. However, strict glycemic control is hard to achieve requiring frequent blood glucose measurements and several insulin injections per day, and in addition is associated with an increased risk of severe hypoglycemia. Recurrent episodes of hypoglycemia, especially at young ages, may cause adverse effects on neurocognitive function, may lead to hypoglycemia unawareness, and may be associated with significant emotional morbidity for the child and parents. Since the discovery of insulin in 1921 there has been constant progress in the way patients with type 1 diabetes are treated. The introduction of recombinant insulin and insulin analogs as well as new insulin delivery systems and glucose monitoring devices enhanced the ability of both patients and medical teams to better define the therapeutic goals and to develop more effective therapeutic strategies. Recent advances in devices for insulin administration and glucose monitoring and the introduction of telemedicine are having a profound effect on the lives of youth with type 1 diabetes. This review focuses on the new technologies which have been developed for treating children and adolescents with type 1 diabetes. PMID- 17727390 TI - The cannabinoid CB(2) receptor: a good friend in the gut. AB - Mammalian tissues express the cannabinoid 1 (CB(1)) receptor and the cannabinoid 2 (CB(2)) receptor, the latter being involved in inflammation and pain. In somatic nerve pathways, the analgesic effects of CB(2) agonism are well documented. Two papers published in the Journal have provided evidence that CB(2) receptor activation inhibits visceral afferent nerve activity in rodents. These exciting findings are discussed in the context of recent data highlighting the emerging role of CB(2) receptor as a critical target able to counteract hypermotility in pathophysiological states, gut inflammation and possibly colon cancer. PMID- 17727391 TI - Assessment of 24-h oesophageal pH monitoring should be divided to awake and asleep rather than upright and supine time periods. AB - Oesophageal acid exposure analysis is divided to upright and supine, based on the assumption that the supine-awake period is similar to the supine-asleep period. To determine if the principal acid-reflux characteristics of supine-awake are closer to supine-asleep or upright period. Patients with heartburn underwent an upper endoscopy and pH testing. The patients were instructed to carefully document their upright, supine-awake and supine-asleep periods. A total of 64 patients were enrolled into this study (M/F 35/29; mean age 52.4 +/- 13.3). The mean percentage total time pH <4, frequency of acid-reflux events (per h) and number of sensed reflux events was not different between upright and the supine awake period (P = ns). In contrast, the mean percentage total time pH <4, frequency of acid-reflux events and number of sensed reflux events was significantly higher in both upright and supine-awake periods vs supine-asleep (4.3 +/- 6.9, 1.86 +/- 2.7 and 0.01 +/- 0.05, P < 0.0001, respectively). The principal characteristics of the acid-reflux events in the supine-awake period are closer to the upright period than to the supine-asleep period. PMID- 17727392 TI - Effects of glucagon-like peptide-1 and sympathetic stimulation on gastric accommodation in humans. AB - In humans, glucagon-like peptide-1 (GLP-1) delays gastric emptying by inhibiting vagal activity and also increases gastric volumes, by unclear mechanisms. Because GLP-1 inhibits intestinal motility by stimulating the sympathetic nervous system in rats, we assessed the effects of a GLP-1 agonist and yohimbine, an alpha(2) adrenergic antagonist, on gastric volumes in humans. In this double-blind study, 32 healthy volunteers were randomized to placebo, a GLP-1 agonist, yohimbine or GLP-1 and yohimbine. Gastric volumes (fasting predrug and postdrug, and postprandial postdrug) were measured by (99m)Tc single photon emission computed tomography imaging. Plasma catecholamines and haemodynamic parameters were assessed. Compared with placebo, GLP-1 increased (P = 0.03) but yohimbine did not affect fasting gastric volume. However, GLP-1 plus yohimbine increased (P < 0.001) postprandial gastric accommodation vs placebo and vs GLP-1 alone [postprandial volume change = 542 +/- 29 mL (mean +/- SEM, placebo), 605 +/- 31 mL (GLP-1), 652 +/- 54 mL (yohimbine) and 810 +/- 37 mL (GLP-1 and yohimbine)]. Plasma noradrenaline and dihydroxyphenylglycol concentrations were higher for yohimbine vs placebo and for GLP-1 and yohimbine vs GLP-1. Yohimbine stimulates central sympathetic activity and in combination with GLP-1, augments postprandial accommodation in humans. PMID- 17727393 TI - Effect of the NK(3) receptor antagonist, talnetant, on rectal sensory function and compliance in healthy humans. AB - Visceral hypersensitivity is important in the pathophysiology of irritable bowel syndrome and thus a target for modulation in drug development. Neurokinin (NK) receptors, including NK(3) receptors, are expressed in the motor and sensory systems of the digestive tract. The aim of this study was to compare the effects of two different doses (25 and 100 mg) of the NK(3) receptor antagonist, talnetant (SB223412) with placebo on rectal sensory function and compliance in healthy volunteers studied at two centres. Rectal barostat tests were performed on 102 healthy volunteers, randomized to receive either oral talnetant 25 or 100 mg or placebo over 14-17 days. Studies were performed on three occasions: day 1 immediately prior to 1st dose, day 1 4 h postdose, and after 14- to17-day therapy. Compliance, and pressure thresholds for first sensation, urgency, discomfort and pain were measured using ascending method of limits, and sensory intensity ratings for gas, urgency, discomfort and pain determined during four random phasic distensions (12, 24, 36 and 48 mmHg). Talnetant had no effect on rectal compliance, sensory thresholds or intensity ratings compared with placebo. In general, the results obtained at the two centres differed minimally, with intensity scores at one centre consistently somewhat lower. At the doses tested, talnetant has no effect on rectal compliance or distension-induced rectal sensation in healthy participants. PMID- 17727394 TI - Cannabinoid type 1 receptor modulates intestinal propulsion by an attenuation of intestinal motor responses within the myenteric part of the peristaltic reflex. AB - Cannabinoid-1 (CB1) receptor activation affects gastrointestinal propulsion in vivo. It was our aim to further characterize the involved myenteric mechanisms in vivo and in vitro. In CB1(-/-) mice and wild-type littermates we performed in vivo transit experiments by charcoal feeding and in vitro electrophysiological recordings in mouse small intestinal smooth muscle. Ascending neuronal contraction (ANC) following electrical field stimulation was studied in rat ileum in a partitioned organ bath separating the aboral stimulation site from the oral recording site. The knockout animals displayed an accelerated upper gastrointestinal transit compared to control animals. The CB1 receptor antagonist AM251 stimulated the force of the ANC in a concentration dependent manner when added in the oral chamber. Anandamide significantly inhibited the ANC when added in the oral chamber. Neither AM251 nor anandamide had an influence on the contraction latency. No effects were observed when drugs were added in the aboral chamber, proving a CB1 mediated action on the neuromuscular junction. Resting membrane potentials and neuronal induced inhibitory junction potentials in CB1(-/ ) mice were unchanged as compared to wild type. However, the electrophysiological slow waves were more sensitive to blockade of Ca(2+) channels in CB1(-/-) mice. Our data strongly suggest a physiological involvement of the CB-1 receptor in the regulation of small intestinal motility. Therefore, CB1 receptors are a promising target for the treatment of motility disorders. PMID- 17727396 TI - Impaired gastric accommodation in children. PMID- 17727395 TI - Long-term colonic hypersensitivity in adult rats induced by neonatal unpredictable vs predictable shock. AB - Our goal was to examine the relationship between early life trauma and the development of visceral hypersensitivity in later life in irritable bowel syndrome (IBS). Rat pups underwent neonatal conditioning: (i) paired odour-shock, where odour is a predictable shock signal, (ii) unpaired odour-shock, where odour is an unpredictable shock signal or (iii) control odour-only with odour presentations and handling without shock. At maturity, colorectal sensitivity was measured as a visceromotor behavioural response. In adulthood, colorectal distension (CRD) induced a pressure-dependent increase in the number of abdominal muscle contractions all three experimental groups. However, compared to animals that had received control odour-only presentations in infancy, there was an attenuated response to CRD in animals previously exposed to neonatal predictable shock pups and an exaggerated response in the animals previously exposed to neonatal unpredictable shock. Adult responses to CRD were altered by infant experience with shock trauma. However, depending on the context of that early life trauma, there are major differences between the long-term effects of that early life trauma on colonic sensitivity compared to controls. These results strengthen the link between early life trauma and adult IBS, and suggest that unpredictable trauma is a critical factor for later life disorders. PMID- 17727398 TI - Multiple rapid swallowing in idiopathic achalasia: from conventional to high resolution manometry. PMID- 17727400 TI - Smoking cessation interventions in chronic obstructive pulmonary disease and the role of the family: a systematic literature review. AB - AIM: This paper is a report of a systematic review to assess the effectiveness of family-focused smoking cessation interventions for people with chronic obstructive pulmonary disease and to determine what data on families are documented in studies of smoking cessation interventions. BACKGROUND: Chronic obstructive pulmonary disease is a major public health problem and cigarette smoking is the most important factor contributing to its development and progression. However, smoking cessation rates are low and relapse is common. The role of families in smoking cessation efforts has received little attention. METHODS: All studies were included in the review that (i) addressed an evaluation of a psycho-social/educational smoking cessation intervention for people with chronic obstructive pulmonary disease, (ii) addressed some information on the family (i.e. living arrangements, marital status, smoking history of family members, support for quitting) and/or included the family as part of the intervention and (iii) were published between 1990 and 2006. Electronic data sources, existing systematic reviews of smoking cessation interventions and the grey literature were reviewed. RESULTS: Seven studies were included. Six studies (11 papers) included data on marital status, smoking status of household members, support for quitting smoking and related variables. In two of the studies, the variable on the family was used to analyse smoking cessation outcomes. One additional study met the inclusion criterion of an evaluation of a smoking cessation intervention, which also included a family focus in the intervention. CONCLUSION: No conclusions about the effectiveness of a family-focused smoking cessation intervention could be drawn from this review. Further research is needed to determine if a more family-focused intervention, in conjunction with pharmacological and counselling approaches, would lead to improved smoking cessation outcomes. PMID- 17727401 TI - The use of bispectral index monitoring in education - a tool to improve nurse anaesthetists practice. AB - AIM: This paper is a report of a study to investigate whether monitoring depth of anaesthesia by bispectral index would reduce recovery time and consumption of anaesthetic drugs in anaesthetics performed by student nurse-anaesthetists. BACKGROUND: It is difficult to assess the depth of anaesthesia clinically. Studies have shown that experienced anaesthetists can titrate anaesthetics more accurately when using bispectral index monitors. It is not known if student nurse anaesthetists can benefit from their use in a similar way. METHOD: A multicentre study involving four hospitals was carried out during a 13-month period in 2003 and 2004. In total 25 nurses participated, each contributing with two procedures: one with monitoring and one without. The nurses had at least 10 months of experience in conducting anaesthesia and all had a theoretical introduction and a test session to become familiar with the equipment. The sequence was randomized and the observer was blinded to whether a monitor was used. Fifty patients were anaesthetized with propofol and fentanyl. Recovery time, consumption of anaesthetic drugs, and patient satisfaction were measured in both groups. RESULTS: Recovery time was 11 minutes in the monitor group (range: 2-53 minutes) and 15 minutes in the control group, (range: 3-60 minutes). P = 0.26. There were no statistically significant differences in consumption of anaesthetic drugs or patient satisfaction in the two groups. CONCLUSION: It was not possible to demonstrate a statistically significant reduction in recovery time or consumption of anaesthetic drugs when using bispectral index monitoring during training of student nurse-anaesthetists. PMID- 17727402 TI - Live my work: rural nurses and their multiple perspectives of self. AB - AIM: This paper is a report of a study to explore rural nurses' experiences of mentoring. BACKGROUND: Mentoring has recently been proposed by governments, advocates and academics as a solution to the problem for retaining rural nurses in the Australian workforce. Action in the form of mentor development workshops has changed the way that some rural nurses now construct supportive relationships as mentoring. METHOD: A grounded theory design was used with nine rural nurses. Eleven semi-structured interviews were conducted in various states of Australia during 2004-2005. Situational analysis mapping techniques and frame analysis were used in combination with concurrent data generation and analysis and theoretical sampling. FINDINGS: Experienced rural nurses cultivate novices through supportive mentoring relationships. The impetus for such relationships comes from their own histories of living and working in the same community, and this was termed 'live my work'. Rural nurses use multiple perspectives of self in order to manage their interactions with others in their roles as community members, consumers of healthcare services and nurses. Personal strategies adapted to local context constitute the skills that experienced rural nurses pass-on to neophyte rural nurses through mentoring, while at the same time protecting them through troubleshooting and translating local cultural norms. CONCLUSION: Living and working in the same community creates a set of complex challenges for novice rural nurses that are better faced with a mentor in place. Thus, mentoring has become an integral part of experienced rural nurses' practice to promote staff retention. PMID- 17727403 TI - Living with early-stage dementia: the perspective of older Chinese people. AB - AIM: This paper is a report of a study to describe the lived experiences of people with early-stage dementia and their ways of coping with the illness. BACKGROUND: Emerging models of subjective experience and coping with early dementia have been developed in Western cultures. Understanding how Chinese people with early-stage dementia adjust and cope is an important starting point in developing interventions that can enhance their adaptive coping. METHOD: A convenience sample of 15 Chinese people in the early stages of dementia were interviewed and observed during home visits. The study involved in-depth transcribed interview data using a phenomenological approach. The data were collected in 2005. RESULTS: Four themes were identified in the data: attribution of illness, experiencing losses resulting in frustration and uncertainty, adapting to a new role in relationships with family and friends and continuing to live. People with early dementia who adopted a positive outlook did so because they had made sense of and accepted the illness, received understanding and support from family and friends and were being listened to and respected. CONCLUSION: The themes emerging from the findings could be used as a framework in understanding how people cope with the onset of early dementia. The framework includes specific implications for the provision of intervention services and highlights the importance of understanding people's own constructions of their illness and how they adjust their lives in coping. PMID- 17727404 TI - How military nurses rationalize their postoperative pain assessment decisions. AB - AIM: This paper is a report of a study to explore how military nurses rationalize their postoperative pain assessment decisions, particularly when these differ from patients' pain self-reports. BACKGROUND: Postoperative pain is a complex phenomenon influenced by many factors that make assessment difficult. Nurses are taught to believe what patients say about their pain. However, their attitudes to pain are influenced by their cultural background and they may disagree with patients' self-reports. Military nurses belong to a military culture with different pain attitudes that may also influence their postoperative pain assessment. METHOD: An ethnomethodological ethnography study was carried out in 2003. A purposive sample of 29 British military surgical/orthopaedic Registered Nurses were interviewed to identify their taken-for-granted assumptions and commonsense cultural knowledge surrounding postoperative pain assessment. The data were analysed using a systematic process of inductive reasoning aided by Non numerical, Unstructured Data for Indexing, Searching and Theorizing (QSR N6, NUD*IST). FINDINGS: Participants told two distinct stories in their postoperative pain narratives. The first, the cultural story, described how military nurses normally assess postoperative pain and revealed taken-for-granted assumptions surrounding this assessment. However, when military nurses believe that patients over- or under-report their pain, the cultural story was challenged through a collective story in which nurses used their commonsense knowledge to account for these differences. CONCLUSION: Postoperative pain assessment within a military culture is complex, but all nurses need to be aware that their socialization into different nursing cultures may influence their attitudes to postoperative pain assessment. PMID- 17727405 TI - Preserving dignity in caring for older adults: a concept analysis. AB - AIM: This paper is a report of a concept analysis of the meaning of preserving dignity. BACKGROUND: Preserving dignity, especially when caring for older adults, is essential when giving nursing care. There is a lack of clarity about what kinds of caring activities lead to preserved dignity. METHOD: Data were collected using several databases (CINAHL, Age Info, Libris, Medline, Pub Med, Psyc INFO and Blackwell Synergy) covering the years 1990-2005. The keywords used were 'dignity', 'human dignity', 'preserving dignity', 'elderly', 'aged', combined with 'patients/persons', 'caring relation' and 'nursing'. The analysis covered 53 articles, dissertations, reports and textbooks. FINDINGS: Dignity may be defined as a concept that relates to basic humanity. Dignity consists of inherent and external dimensions, which are common for all humans and at the same time are unique for each person, relating to social and cultural aspects. The attributes of preserving dignity are individualized care, control restored, respect, advocacy and sensitive listening. Antecedents are professional knowledge, responsibility, reflection and non-hierarchical organization. The consequences are strengthening life spirit, an inner sense of freedom, self-respect and successful coping. CONCLUSION: Preserving an older adult's dignity is complex. By using the attributes in, for example, nursing documentation, the action and value of preserving dignity could be made visible as a professional nursing activity. PMID- 17727406 TI - A concept analysis of renal supportive care: the changing world of nephrology. AB - AIM: This paper is a report of a concept analysis of renal supportive care. BACKGROUND: Approximately 1.5 million people worldwide are kept alive by renal dialysis. As services are required to support patients who decide not to start or to withdraw from dialysis, the term renal supportive care is emerging. Being similar to the terms palliative care, end-of-life care, terminal care and conservative management, there is a need for conceptual clarity. METHOD: Rodgers' evolutionary method was used as the organizing framework for this concept analysis. Data were collected from a review of CINAHL, Medline, PsycINFO, British Nursing Index, International Bibliography of the Social Sciences and ASSIA (1806 2006) using, 'renal' and 'supportive care' as keywords. All articles with an abstract were considered. The World Wide Web was also searched in English utilizing the phrase 'renal supportive care'. RESULTS: Five attributes of renal supportive care were identified: available from diagnosis to death with an emphasis on honesty regarding prognosis and impact of disease; interdisciplinary approach to care; restorative care; family and carer support and effective, lucid communication to ensure informed choice and clear lines of decision-making. CONCLUSION: Renal supportive care is a dynamic and emerging concept relevant, but not limited to, the end phase of life. It suggests a central philosophy underpinning renal service development that allows patients, carers and the multidisciplinary team time to work together to realize complex goals. It has relevance for the renal community and is likely to be integrated increasingly into everyday nephrology practice. PMID- 17727412 TI - The contribution of mosses to the carbon and water exchange of Arctic ecosystems: quantification and relationships with system properties. AB - Water vapour and CO2 exchange were measured in moss-dominated vegetation using a gas analyser and a 0.3 x 0.3 m chamber at 17 sites near Abisko, Northern Sweden and 21 sites near Longyearbyen, Svalbard, to quantify the contribution of mosses to ecosystem level fluxes. With the help of a simple light-response model, we showed that the moss contribution to ecosystem carbon uptake varied between 14 and 96%, with an average contribution of around 60%. This moss contribution could be related to the normalized difference vegetation index (NDVI) of the vegetation and the leaf area index (LAI) of the vascular plants. NDVI was a good predictor of gross primary production (GPP) of mosses and of the whole ecosystem, across different moss species, vegetation types and two different latitudes. NDVI was also correlated with thickness of the active green moss layer. Mosses played an important role in water exchange. They are expected to be most important to gas exchange during spring when leaves are not fully developed. PMID- 17727413 TI - Allometric analysis reveals relatively little variation in nitrogen versus biomass accrual in four plant species exposed to varying light, nutrients, water and CO2. AB - Nitrogen concentrations in plant tissues can vary as a function of resource availability. Altered rates of plant growth and development under varying resource availabilities were examined to determine their effects on changes in whole-plant N use efficiency (NUE). Three species of old-field annuals were grown at broadly varying light, nutrient and water levels, and four species at varying atmospheric concentrations of CO2. Study results show highly variable N accrual rates when expressed as a function of plant age or size, but similar patterns of whole-plant N versus non-N biomass accrual over a wide range of environmental conditions. However, severely light-limited plants showed increased N versus biomass accrual for two of three species, and severely nutrient-limited plants had decreased N versus biomass accrual for all species. Whole-plant N accrual versus age and N versus biomass accrual increased under saturating water for two of three species. A marginally significant, modest decrease in N versus biomass accrual was found at high CO2 levels for two of four species. Physiological adjustments in NUE, expressed as N versus biomass accrual, were limited to environments with severely limited or overabundant resources. PMID- 17727414 TI - Diurnal, seasonal and interannual variability of carbon isotope discrimination at the canopy level in response to environmental factors in a boreal forest ecosystem. AB - Accurate estimation of temporal and spatial variations in photosynthetic discrimination of 13C is critical to carbon cycle research. In this study, a combined ecosystem-boundary layer isotope model, which was satisfactorily validated against intensive campaign data, was used to explore the temporal variability of carbon discrimination in response to environmental driving factors in a boreal ecosystem in the vicinity of Fraserdale Tower, Ontario, Canada (49 degrees 52'30''N, 81 degrees 34'12''W). A 14 year (1990-1996 and 1998-2004) hourly CO2 concentration and meteorological record measured on this tower was used for this purpose. The 14 year mean yearly diurnal amplitude of canopy-level discrimination Delta(canopy) was computed to be 2.8 +/- 0.5 per thousand, and the overall diurnal cycle showed that the greatest Delta(canopy) values occurred at dawn and dusk, while the minima generally appeared in mid-afternoon. The average annual Delta(canopy) varied from 18.3 to 19.7 per thousand with the 14 year average of 19 +/- 0.4 per thousand. The overall seasonality of Delta(canopy) showed a gradually increasing trend from leaf emergence in May-September and with a slight decrease at the end of the growing season in October. Delta(canopy) was negatively correlated to vapour pressure deficit and air temperature across hourly to decadal timescales. A strong climatic control on stomatal regulation of ecosystem isotope discrimination was found in this study. PMID- 17727415 TI - Photosynthetic recovery following desiccation of desert green algae (Chlorophyta) and their aquatic relatives. AB - Recent molecular data suggest that desert green algae have evolved from freshwater ancestors at least 14 times in three major classes (Chlorophyceae, Trebouxiophyceae and Charophyceae), offering a unique opportunity to study the adaptation of photosynthetic organisms to life on land in a comparative phylogenetic framework. We examined the photorecovery of phylogenetically matched desert and aquatic algae after desiccation in darkness and under illumination. Desert algae survived desiccation for at least 4 weeks when dried in darkness, and recovered high levels of photosynthetic quantum yield within 1 h of rehydration in darkness. However, when 4 weeks of desiccation was accompanied by illumination, three of six desert taxa lost their ability to recover quantum yield during rehydration in the dark. Aquatic algae, in contrast, recovered very little during dark rehydration following even just 24 h of desiccation. Re illuminating rehydrated algae produced a nearly complete recovery of quantum yield in all desert and two of five aquatic taxa. These contrasts provide physiological evidence that desert green algae possess mechanisms for photosynthetic recovery after desiccation distinct from those in aquatic relatives, corroborating molecular evidence that they are not happenstance, short term visitors from aquatic environments. Photosensitivity during desiccation among desert algae further suggests that they may reside in protected microsites within crusts, and species specificity of photosensitivity suggests that disturbances physically disrupting crusts could lead to shifts or losses of taxonomic diversity within these habitats. PMID- 17727416 TI - Genetic variation in pea (Pisum sativum L.) demonstrates the importance of root but not shoot C/N ratios in the control of plant morphology and reveals a unique relationship between shoot length and nodulation intensity. AB - Nodule numbers are regulated through systemic auto-regulatory signals produced by shoots and roots. The relative effects of shoot and root genotype on nodule numbers together with relationships to organ biomass, carbon (C) and nitrogen (N) status, and related parameters were measured in pea (Pisum sativum) exploiting natural genetic variation in maturity and apparent nodulation intensity. Reciprocal grafting experiments between the early (Athos), intermediate (Phonix) and late (S00182) maturity phenotypes were performed and Pearson's correlation coefficients for the parameters were calculated. No significant correlations were found between shoot C/N ratios and plant morphology parameters, but the root C/N ratio showed a strong correlation with root fresh and dry weights as well as with shoot fresh weight with less significant interactions with leaf number. Hence, the root C/N ratio rather than shoot C/N had a predominant influence on plant morphology when pea plants are grown under conditions of symbiotic nitrogen supply. The only phenotypic characteristic that showed a statistically significant correlation with nodulation intensity was shoot length, which accounted for 68.5% of the variation. A strong linear relationship was demonstrated between shoot length and nodule numbers. Hence, pea nodule numbers are controlled by factors related to shoot extension, but not by shoot or root biomass accumulation, total C or total N. The relationship between shoot length and nodule numbers persisted under field conditions. These results suggest that stem height could be used as a breeding marker for the selection of pea cultivars with high nodule numbers and high seed N contents. PMID- 17727417 TI - Increase in respiratory cost at high growth temperature is attributed to high protein turnover cost in Petunia x hybrida petals. AB - It is widely believed that turnover of nitrogenous (N) compounds (especially proteins) incurs a high respiratory cost. Thus, if protein turnover costs change with temperature, this would influence the dependence of respiration rate on growth temperature. Here, we examined the extent to which protein turnover cost explained differences in N-utilization costs (nitrate uptake/reduction, ammonium assimilation, amino acid and protein syntheses, protein turnover and amino acid export) and in respiration rate with changes in growth temperature. By measurements and literature data, we evaluated each N-utilization cost in Petunia x hybrida petals grown at 20, 25 or 35 degrees C throughout their whole lifespans. Protein turnover cost accounted for 73% of the integrated N utilization cost on a whole-petal basis at 35 degrees C. The difference in this cost on a dry weight basis between 25 and 35 degrees C accounted for 75% of the difference in N-utilization cost and 45% of the difference in respiratory cost. The cost of nitrate uptake/reduction was high at low growth temperatures. We concluded that respiratory cost in petals was strongly influenced by protein turnover and nitrate uptake/reduction, and on the shoot basis, C investment in biomass was highest at 25 degrees C. PMID- 17727418 TI - Rapid variations of mesophyll conductance in response to changes in CO2 concentration around leaves. AB - The effects of short-term (minutes) variations of CO2 concentration on mesophyll conductance to CO2 (gm) were evaluated in six different C3 species by simultaneous measurements of gas exchange, chlorophyll fluorescence, online carbon isotope discrimination and a novel curve-fitting method. Depending on the species, gm varied from five- to ninefold, along the range of sub-stomatal CO2 concentrations typically used in photosynthesis CO2-response curves (AN)-Ci curves; where AN is the net photosynthetic flux and Ci is the CO2 concentrations in the sub-stomatal cavity), that is, 50 to 1500 micromol CO2 mol(-1) air. Although the pattern was species-dependent, gm strongly declined at high Ci, where photosynthesis was not limited by CO2, but by regeneration of ribulose-1,5 bisphosphate or triose phosphate utilization. Moreover, these changes on gm were found to be totally independent of the velocity and direction of the Ci changes. The response of gm to Ci resembled that of stomatal conductance (gs), but kinetic experiments suggested that the response of gm was actually faster than that of gs. Transgenic tobacco plants differing in the amounts of aquaporin NtAQP1 showed different slopes of the gm-Ci response, suggesting a possible role for aquaporins in mediating CO2 responsiveness of gm. The importance of these findings is discussed in terms of their effects on parameterization of AN-Ci curves. PMID- 17727419 TI - A stereo imaging system for measuring structural parameters of plant canopies. AB - Plants constantly adapt their leaf orientation in response to fluctuations in the environment, to maintain radiation use efficiency in the face of varying intensity and incidence direction of sunlight. Various methods exist for measuring structural canopy parameters such as leaf angle distribution. However, direct methods tend to be labour-intensive, while indirect methods usually give statistical information on stand level rather than on individual leaves. We present an area-based, binocular stereo system composed of commercially available components that allows three-dimensional reconstruction of small- to medium-sized canopies on the level of single leaves under field conditions. Spatial orientation of single leaves is computed with automated processes using modern, well-established stereo matching and segmentation techniques, which were adapted for the properties of plant canopies, providing high spatial and temporal resolution (angle measurements with an accuracy of approx. +/-5 degrees and a maximum sampling rate of three frames per second). The applicability of our approach is demonstrated in three case studies: (1) the dihedral leaflet angle of an individual soybean was tracked to monitor nocturnal and daytime leaf movement showing different frequencies and amplitudes; (2) drought stress was diagnosed in soybean by quantifying changes in the zenith leaflet angle distribution; and (3) the diurnal course of the zenith leaf angle distribution of a closed soybean canopy was measured. PMID- 17727420 TI - Kinetics of NO3(-) net fluxes in Pinus pinaster, Rhizopogon roseolus and their ectomycorrhizal association, as affected by the presence of NO3(-) and NH4+. AB - The impact of mineral N supply, N-free or NO3(-) with or without NH4+, on the subsequent uptake of NO3(-) by maritime pine seedlings associated with the ectomycorrhizal fungus Rhizopogon roseolus was studied using ion-selective microelectrodes. NO3(-) net fluxes into N-starved non-mycorrhizal short roots (NMSRs) were low and measurable only over the NO3(-) concentration range of 0-70 microM. The simple kinetics observed in those roots may reflect the dominant operation of a high-affinity NO3(-) transport system (HATS) which is constitutive. NO3(-) pretreatment increased the NO3(-) net fluxes and led to a complex kinetics that may reflect the operation of other HATS. A simple kinetics was observed in plants pre-incubated at high NH4+ concentration. In contrast, NO3(-) uptake kinetics presented only one saturation phase in the fungus, whether associated with the plant or not. NO3(-) uptake was greater after a pretreatment in N-free or NO3 (-) solution, but NH4+ pretreatment led to a threefold reduction in NO3 (-) uptake. These results suggest that the regulation of NO3(-) transport systems varies between the host and the fungal partner. This variation is likely to contribute to the positive effect of mycorrhizal association on N uptake in plants when the N supply is low and fluctuating. PMID- 17727421 TI - Reactive oxygen species and nitric oxide are involved in ABA inhibition of stomatal opening. AB - Although nitric oxide (NO) and reactive oxygen species (ROS) are essential signalling molecules required for mediation of abscisic acid (ABA)-induced stomatal closure, it is not known whether these molecules also mediate the ABA inhibition of stomatal opening. In this study, we investigated the role of NO and ROS in the ABA inhibition of stomatal opening in Vicia faba. ABA induced both NO and ROS synthesis, and the NO scavenger reduced the ABA inhibition of stomatal opening. Exogenous NO and hydrogen peroxide (H2O2) also inhibited stomatal opening, indicating that NO and ROS are involved in the inhibition signalling process. An inhibitor of nitric oxide synthase (NOS) reversed the ABA inhibition of stomatal opening. Either the NO scavenger or the NOS inhibitor also reversed the process in the H2O2 inhibition of stomatal opening. We found that in the ABA inhibition of stomatal opening, NO is downstream of ROS in the signalling process, and NO is synthesized by a NOS-like enzyme. PMID- 17727422 TI - Root growth dynamics of Nicotiana attenuata seedlings are affected by simulated herbivore attack. AB - Many studies demonstrate resource-based trade-offs between growth and defence on a large timescale. Yet, the short-term dynamics of this growth reaction are still completely unclear, making it difficult to explain growth-defence trade-offs mechanistically. In this study, image-based non-destructive methods were used to quantify root growth reactions happening within hours following simulated herbivore attack. The induction of wound reactions in Nicotiana attenuata in the seedling stage led to transiently decreased root growth rates. Application of the oral secretion of the specialist herbivore Manduca sexta to the leaves led to a transient decrease in root growth that was more pronounced than if a mere mechanical wounding was imposed. Root growth reduction was more pronounced than leaf growth reduction. When fatty acid-amino acid conjugates (FACs) were applied to wounds, root growth reduction occurred in the same intensity as when oral secretion was applied. Timing of the transient growth reduction coincided with endogenous bursts of jasmonate (JA) and ethylene emissions reported in literature. Simulation of a wound response by applying methyl jasmonate (MeJA) led to more prolonged negative effects on root growth. Increased nicotine concentrations, trichome lengths and densities were observed within 72 h in seedlings that were treated with MeJA or that were mechanically wounded. Overall, these reactions indicate that even in a very early developmental stage, the diversion of plant metabolism from primary (growth-sustaining) to secondary (defence-related) metabolism can cause profound alterations of plant growth performance. PMID- 17727423 TI - The functional significance of C3-C4 intermediate traits in Heliotropium L. (Boraginaceae): gas exchange perspectives. AB - We demonstrate for the first time the presence of species exhibiting C3-C4 intermediacy in Heliotropium (sensu lato), a genus with over 100 C3 and 150 C4 species. CO2 compensation points (Gamma) and photosynthetic water-use efficiencies (WUEs) were intermediate between C3 and C4 values in three species of Heliotropium: Heliotropium convolvulaceum (Gamma = 20 micromol CO2 mol(-1) air), Heliotropium racemosum (Gamma = 22 micromol mol(-1)) and Heliotropium greggii (Gamma = 17 micromol mol(-1)). Heliotropium procumbens may also be a weak C3-C4 intermediate based on a slight reduction in Gamma (48.5 micromol CO2 mol( 1)) compared to C3Heliotropium species (52-60 micromol mol(-1)). The intermediate species H. convolvulaceum, H. greggii and H. racemosum exhibited over 50% enhancement of net CO2 assimilation rates at low CO2 levels (200-300 micromol mol(-1)); however, no significant differences in stomatal conductance were observed between the C3 and C3-C4 species. We also assessed the response of Gamma to variation in O2 concentration for these species. Heliotropium convolvulaceum, H. greggii and H. racemosum exhibited similar responses of Gamma to O2 with response slopes that were intermediate between the responses of C3 and C4 species below 210 mmol O2 mol(-1) air. The presence of multiple species displaying C3-C4 intermediate traits indicates that Heliotropium could be a valuable new model for studying the evolutionary transition from C3 to C4 photosynthesis. PMID- 17727424 TI - Patients with hepatitis C are best managed by a specialist in liver diseases. PRO: Management of hepatitis C by liver disease specialists. PMID- 17727426 TI - Patients with hepatitis C are best managed by a specialist in liver diseases. CON: The management of hepatitis C in a community-based practice. PMID- 17727427 TI - A balancing view: We cannot do it alone. PMID- 17727428 TI - Acute phosphate nephropathy--an emerging issue. AB - Acute phosphate nephropathy is an accepted complication of the use of phosphate preparations in patients about to undergo colonoscopy. Age, renal failure, and the ongoing use of medications, such as angiotensin-converting enzyme inhibitors and/or angiotensin-receptor blockers, are now recognized as risk factors for the development of phosphate nephropathy. The presence of any of these risk factors necessitates careful attention to avoiding excessive dehydration in the process of bowel cleansing. In so doing, the likelihood of acute phosphate nephropathy occurring can be lessened. PMID- 17727429 TI - On mentoring. PMID- 17727430 TI - Sporadic gastric cancer; a complex interaction of genetic and environmental risk factors. AB - Sporadic gastric cancer usually arises against a background of sequential mucosal changes. H. pylori superficial gastritis progresses to atrophy and intestinal metaplasia and then to dysplasia and cancer. A variety of environmental and host genetic factors influence this process and act at different stages in the pathway. Many different combinations of these risk factors may lead to cancer. Interactions also occur between environmental and genetic factors to increase or decrease their ability to influence the precancerous process. Sporadic gastric cancer is thus the consequence of complex combinations and interactions between many environmental and genetic factors. PMID- 17727431 TI - Driving with minimal hepatic encephalopathy: real world consequences? AB - Mounting evidence suggests that minimal hepatic encephalopathy of cirrhosis may compromise driving performance. A study now reveals that patients with minimal hepatic encephalopathy had a greater self-reported frequency of motor vehicle accidents and traffic violations. There are still numerous issues to be resolved before this increasingly recognized variant of hepatic encephalopathy can be firmly linked to hazardous driving. Minimal hepatic encephalopathy affects a substantial proportion of patients with otherwise well-compensated cirrhosis, and because therapies are effective in reversing this type of encephalopathy, its role in motor vehicle accidents deserves further attention. PMID- 17727436 TI - Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. PMID- 17727438 TI - Is indomethacin a new hope for post-ERCP pancreatitis? PMID- 17727439 TI - Bravo capsule for wireless 48-h pH monitoring: proposed algorithm for its placement. PMID- 17727440 TI - Columnar-lined esophagus: lessons learnt from children. PMID- 17727444 TI - Uninvestigated dyspepsia or functional dyspepsia: that is the question. PMID- 17727443 TI - Treatment interruptus: the need for withdrawal. PMID- 17727445 TI - Inactivation of digestive proteases: another mechanism that probiotics may have conferred a protection. PMID- 17727446 TI - Refractory benign esophageal stricture. PMID- 17727447 TI - Anti-reflux surgery is superior to medical management in patients with Barrett's esophagus with low-grade dysplasia. PMID- 17727448 TI - Act instead of wait: consequences of novel Barrett's--histopathology. PMID- 17727449 TI - The Indian enigma of frequent H. pylori infection but infrequent gastric cancer: is the magic key in Indian diet, host's genetic make up, or friendly bug? PMID- 17727450 TI - Indian enigma? Reanalyzed data are less than supportive. PMID- 17727452 TI - Epidemiology of Helicobacter pylori infection. AB - Helicobacter pylori infection is typically acquired in early childhood in both low- and high-income regions of the world and, once established, commonly persists lifelong unless treated. Social and economic development decreases the prevalence both within and between countries. The epidemiology of H. pylori infection highlights the geographic, ethnic, and racial differences throughout the world. PMID- 17727453 TI - Diagnosis of Helicobacter pylori. AB - Although there are attempts to perform Helicobacter pylori diagnosis directly in vivo using magnification endoscopy, most articles on diagnosis this year concerned non-invasive tests and molecular methods. For urea breath tests, there are attempts to have a quicker and cheaper test and to evaluate its role in cases of premalignant lesions. For stool antigens tests, evaluation of kits using monoclonal antibodies was carried out. Molecular tests have been applied for typing and detection of resistant mutants. PMID- 17727454 TI - Pathogenesis of Helicobacter pylori infection. AB - The clinical outcome of Helicobacter pylori infection is determined by a complex interaction between the bacterium and the host. The main bacterial factors associated with pathogenicity comprise outer membrane proteins, including BabA, SabA, OipA, AlpA, and AlpB, the vacuolating cytotoxin VacA and the products of cagPAI. The multitude of putative virulence factors makes it extremely difficult to test the contribution of each individual factor. Much effort has been put into identifying the mechanism associated with H. pylori-associated carcinogenesis. Interaction between bacterial factors such as CagA and host signal transduction pathways seems to be critical for mediating cell transformation, cell proliferation, invasion, apoptosis/anti-apoptosis, and angiogenesis. An animal model using the Mongolian gerbil is a useful model for showing gastric pathology due to H. pylori infection which is similar to that in humans and can be used to evaluate virulence factors including CagA, host responses, and environmental factors such as salt intake. PMID- 17727455 TI - Helicobacter pylori inflammation, immunity, and vaccines. AB - Helicobacter pylori infects almost 50% of the world population and is the major cause of gastroduodenal diseases. H. pylori colonizes the gastric mucosa, activates Toll-like and Nod-like receptors, and usually elicits a T helper 1 (Th1) type of immune response, fully polarized in peptic ulcer patients. Among several bacterial factors, the neutrophil-activating protein represents a key factor driving Th1 inflammation. A complex and fascinating balance between H. pylori and host factors takes part in the gastric niche and allows the majority of infected individuals to be without any symptom during their entire life. Novel insights into the innate and adaptive responses against H. pylori, dealing with regulatory T cells and cytokines, CTLA-4 molecule, cholesterol glucosylation, and immune evasion have been elucidated during the past year and are discussed for the development of an effective vaccine. PMID- 17727456 TI - Helicobacter pylori and non-malignant diseases. AB - In recent years, the focus of Helicobacter pylori clinical research has been mainly on gastric malignancy. However, the role of H. pylori in non-malignant diseases, such as peptic ulcer, gastroesophageal reflux disease (GERD) and non ulcer dyspepsia, as well as non-steroidal anti-inflammatory drug consumption, is still of great interest. A 1- to 2-week course of H. pylori eradication therapy is an effective treatment for H. pylori-positive peptic ulcer disease and a positive CagA status is a predictor for successful eradication of H. pylori. Antral prostaglandin-E2-basal levels appear to be critical for the development of aspirin-induced gastric damage in subjects without H. pylori infection. In clinical practice, among patients treated with proton-pump inhibitors, H. pylori status has no effect on the speed or degree of GERD symptom relief. For the management of dyspepsia in primary care, antisecretory therapy confers a small insignificant benefit compared to strategies based on H. pylori testing while these latter strategies may be cost-effective. H. pylori eradication therapy has a small but statistically significant effect on H. pylori-positive non-ulcer dyspepsia. An economic model suggests that this modest benefit may still be cost effective but more research is needed. PMID- 17727457 TI - Helicobacter and gastric malignancies. AB - Over the past year Helicobacter pylori has been confirmed as the most important risk factor for non-cardia gastric adenocarcinomas and gastric mucosa-associated lymphoid tissue (MALT) lymphomas. Eradication therapy has been proven to be beneficial when given prior to the development of intestinal metaplasia, but is less efficacious when administered later. However, the best data from clinical trials indicate that H. pylori eradication alone will have only a moderate effect on gastric cancer incidence worldwide. The mechanisms responsible for H. pylori associated gastric carcinogenesis continue to be dissected. Accumulating evidence suggests that some H. pylori may be able to invade through the gastric epithelial barrier, though pro-carcinogenic effects may also be related to the complex and evolving pathways of altering signal transduction pathways within gastric epithelial cells that are stimulated by adherence and translocation of H. pylori products through its type IV secretory system. Determinants of the host response to H. pylori infection continue to focus on polymorphisms in genes related to the innate and acquired immune responses, including NOD2, COX-2, and TLR-4. H. pylori eradication is indicated for low-grade gastric B-cell MALT lymphoma and may even provide "cure" in some apparently H. pylori-negative cases. How and why does H. pylori promote lymphomagenesis? Some evidence from human and murine models points to specific chromosomal translocations and host genetic polymorphisms as relating to the outcome of infection. Finally, Helicobacter hepaticus infection has been linked to both intestinal and breast tumorigenesis in susceptible strains of female mice - a provocative and novel finding warranting further investigation. PMID- 17727458 TI - Treatment of Helicobacter pylori. AB - Since the discovery of Helicobacter pylori in the early 1980s many treatment regimes have been developed to effectively treat this infection. International guidelines have allowed consensus on the best management and improved eradication rates. In recent years, increasing antimicrobial resistance has resulted in falling eradication rates with standard therapies. In this article, we review the most recent studies and guidelines in the treatment of H. pylori. Currently, the first-line treatment remains clarithromycin, amoxicillin or metronidazole and proton pump inhibitor twice daily, but a number of recent studies have shown low eradication rates with this treatment. Increased duration of therapy has been recommended to overcome the falling eradication rates. However, conflicting findings have been reported on the benefits of extending the length of traditional therapy. Sequential therapy may be an effective alternative to standard triple therapy in regions of increased antimicrobial resistance. Probiotics reduce side-effects from traditional regimens and may improve eradication rates. A quinolone-based second-line triple therapy appears to be effective and well tolerated. Bismuth-based quadruple therapy is also an effective alternative if available. In the future, regional antimicrobial resistance and eradication rates will determine the best treatment for H. pylori. PMID- 17727459 TI - Helicobacter pylori infection in pediatrics. AB - During the last year, epidemiologic studies have shown that spontaneous clearance of Helicobacter pylori infection has a less significant role in countries with high prevalence and, in contrast to adults, there is no male predominance of H. pylori infection in children. Early acquisition of H. pylori may play a role in the development of recurrent abdominal pain in children less than 5 years of age. In this very young age group, the adequate performance of stool antigen test and (13)C urea-breath test demonstrated satisfactory sensitivity and specificity as non-invasive methods to diagnose H. pylori infection. In the current paper, the most relevant pediatric studies on H. pylori infection published between April 2006 and March 2007 are reviewed. PMID- 17727460 TI - Extragastric manifestations of Helicobacter pylori infection -- other Helicobacters. AB - Today there is evidence that Helicobacter pylori has a critical role in different extragastric diseases. The discovery of a number of other novel Helicobacter species has stimulated the research in different extragastric diseases, in which an infectious hypothesis is plausible. Enterohepatic Helicobacter species have been hypothesized to play a role in different disorders, including hepatocellular carcinoma, gallstones formation and cholangiocellular carcinoma, as well as enteric diseases and inflammatory bowel diseases. Concerning the extragastric manifestations of H. pylori infection, idiopathic thrombocytopenic purpura, and sideropenic anemia represent, based on the current data, the diseases in which the pathogenic link appears to be strongest. There is also an increasing evidence for a possible association of H. pylori with cardiovascular disease. PMID- 17727461 TI - Scar formation. Introduction. PMID- 17727462 TI - Bone marrow-derived stem cells in wound healing: a review. AB - Optimum healing of a cutaneous wound requires a well-orchestrated integration of the complex biological and molecular events of cell migration and proliferation, and of extracellular matrix deposition and remodeling. Several studies in recent years suggest that bone marrow derived stem cells such as mesenchymal stem cells, progenitor cells such as endothelial progenitor cells and fibrocytes may be involved in these processes, contributing to skin cells or releasing regulatory cytokines. Stem/progenitor cells may be mobilized to leave the bone marrow, home to injured tissues and participate in the repair and regeneration. Direct injection of bone marrow derived mesenchymal stem cells or endothelial progenitor cells into injured tissues shows improved repair through mechanisms of differentiation and/or release of paracrine factors. Enhanced understanding of these cells may help develop novel therapies for difficult cutaneous conditions such as non-healing chronic wounds and hypertrophic scarring as well as engineering cutaneous substitutes. PMID- 17727463 TI - Consequences of excessive scar formation: dealing with the problem and aiming for the future. AB - Scarring is the major hindrance to the healing of all tissues. Unfortunately, our knowledge about the factors that regulate scarring is quite limited. Even worse is the fact that there have been few gains in the treatment of pathologic scarring. This review sets the stage for the supplement on scar formation that provides the latest knowledge on the pathophysiology and treatment of scar formation. PMID- 17727464 TI - Making sense of hypertrophic scar: a role for nerves. AB - Healed partial thickness wounds including burns and donor sites cause hypertrophic scar formation and patient discomfort. For many patients with hypertrophic scars, pruritus is the most distressing symptom, which leads to wound excoriation and chronic wound formation. In spite of the clinical significance of abnormal innervation in scars, the nervous system has been largely ignored in the pathophysiology of hypertrophic scars. Evidence that neuropeptides contribute to inflammatory responses to injury include inflammatory cell chemotaxis, cytokine and growth factor production. The neuropeptide substance P, which is released from nerve endings after injury, induces inflammation and mediates angiogenesis, keratinocyte proliferation, and fibrogenesis. Substance P activity is tightly regulated by neutral endopeptidase (NEP), a membrane bound metallopeptidase that degrades substance P at the cell membrane. Altered substance P levels may contribute to impaired cutaneous healing responses associated with diabetes mellitus or hypertrophic scar formation. Topical application of exogenous substance P or an NEP inhibitor enhances wound closure kinetics in diabetic murine wounds suggesting that diabetic wounds have insufficient substance P levels to promote a neuroinflammatory response necessary for normal wound repair. Conversely, increased nerve numbers and neuropeptide levels with reduced NEP levels in human and porcine hypertrophic scar samples suggest that excessive neuropeptide activity induces exuberant inflammation in hypertrophic scars. Given these observations about the role of neuropeptides in cutaneous repair, neuronal modulation of repair processes at two extremes of abnormal wound healing, chronic non-healing ulcers in type II diabetes mellitus and hypertrophic scars in deep partial thickness wounds, may provide therapeutic targets. PMID- 17727466 TI - Hypertrophic scar model in the rabbit ear: a reproducible model for studying scar tissue behavior with new observations on silicone gel sheeting for scar reduction. AB - Hypertrophic scarring poses a clinically relevant problem as it can be cosmetically disfiguring and functionally debilitating. A lack of animal models has hindered an understanding of the pathogenesis and development of new treatment strategies therefore has largely been empiric. Our group has developed a unique hypertrophic scar (HS) model in the rabbit ear. The model has been reproducible, quantifiable, and measurable over a time period of 1 month. We describe the development as well as the reliability and responsiveness of this model to different therapeutic agents, such as TGF-beta blockade, silicone occlusion, and application of collagen-synthesis inhibitors. Moreover, it has given insights into the mechanism of action of silicone sheeting occlusive treatment and ultimately suggests that the epidermis plays a critical role in the development of HS. Additionally, we will present new data supporting the importance of the epidermis and further clarify the mechanism of action of silicone sheeting. When a semi-occlusive polyurethane film was left in place for an additional time period, scar formation was reduced. HSs of this model covered with silicone sheets and five layers of Tegaderm showed a significant scar reduction by 80% compared with wounds with only one layer of Tegaderm. The HS model in the rabbit ear is a highly reliable, responsive, and practical model for studying scar tissue behavior. Furthermore, our data suggest that the degree and the duration of occlusion are most important for reducing scar tissue formation. PMID- 17727467 TI - Role of keratinocyte-fibroblast cross-talk in development of hypertrophic scar. AB - The ability to generate or repair injured tissue is essential to the continuity of human life. As in all other organs, wound healing in the skin is a dynamic process involving tissue response to different types of insults. This process involves a continuous sequence of signals and responses in which platelets, fibroblasts, epithelial, endothelial, and immune cells come together outside their usual domains to orchestrate a very complex event that results in tissue repair. These signals, which are mainly growth factors and cytokines, orchestrate the initiation, continuation, and termination of wound healing. An imbalance in the synthesis and release of these cytokines and growth factors at the wound site, therefore, may result in either retarded wound healing, as is seen in diabetic patients and the elderly population, or overhealing wounds such as fibroproliferative disorders frequently seen following surgical incision, traumatic wounds, and severe electrical and thermal injury. In general, regardless of the site of injury, in any phase of the dynamic healing process, a fine balance between synthesis of extracellular matrix and degradation by a large family of enzymes, known as matrix metalloproteinases, is required for maintaining the structural integrity of healing tissue. The availability of new models such as organotypic co-culture systems have allowed us to gain new insight into the cell-cell interactions at both cellular and molecular levels. Recent evidence indicates that mesenchymal-epithelial interactions play a critical role in regulation of skin homeostasis and this cross-talk is mediated by soluble factors acting as autocrine/paracrine regulators of fibroblast and keratinocyte growth, function, and differentiation. In this review we address the question of how keratinocyte-fibroblast interaction plays a role in controlling the expression of key extracellular matrix molecules such as matrix metalloproteinases, which are critical in the healing process following any types of insults to the skin. PMID- 17727465 TI - Review of the female Duroc/Yorkshire pig model of human fibroproliferative scarring. AB - Hypertrophic scarring after burns is an unsolved problem and remains as devastating today as it was in the 40s and it may be that the main reason for this is the lack of an accepted, useful animal model. The female, red Duroc pig was described as a model of hypertrophic scarring nearly 30 years ago but then vanished from the literature. This seemed strange since the authors reported that 12 of 12 pigs developed thick scar. In the mid 90s we explored the model and found that, indeed, the red Duroc pig does make thick scar. Other authors have established that the Yorkshire pig does not heal in this fashion so there is the possibility of a same species control. We have continued to explore the Duroc/Yorkshire model and herein describe our experiences. Is it a perfect model of hypertrophic scarring? No. Is it a useful model of hypertrophic scarring? Time will tell. We have now obtained gene expression data from the Duroc/Yorkshire model and analysis is underway. PMID- 17727468 TI - TGF-beta-induced fibrosis and SMAD signaling: oligo decoys as natural therapeutics for inhibition of tissue fibrosis and scarring. AB - Transforming-growth factor-beta (TGF-beta) is a pleiotrophic growth factor that is synthesized by many cells in the body. This growth factor is chemotactic for fibroblasts, stimulates fibroblast proliferation, and increases the synthesis of a number of extracellular matrix proteins including collagens. The TGF-beta activator protein is a transacting factor, which binds to the TGF-beta element in the distal promoter of the COL1A1 collagen gene and induces transcription of this gene. Although transient TGF-beta 1 activity participates in repair and regeneration of tissues, persistent TGF-beta 1 function affects excessive fibrosis and ultimately scarring of both skin and internal organs. Scarring of internal organ (e.g., liver and lung) results in a loss of function and ultimately death may occur. The central issue of this review is that phosphorothioate double-stranded decoys or other decoys decrease procollagen gene expression, procollagen synthesis, and collagen during fibrogenesis. The rationale is that the decoys containing the TGF-beta element or other gene transcription regulatory CIS-elements bind the transacting proteins preventing the latter from binding to the CIS-element in the 5'-flanking region of the natural gene resulting in transcription inhibition. We will, in part, focus on aspects involved in TGF-beta 1-induced fibrosis that occur during fibrogenesis and the use of the dsTGF-beta element containing oligodeoxynucleotide decoys to control excessive collagen synthesis, and deposition resulting from persistent TGF-beta. In our model of regulation of collagen synthesis, these double-stranded oligo decoys act as promoter competitors, binding to the activator protein either in the cytoplasm or in the nucleus. The significance of the proposed studies is that these novel natural antifibrotics will mimic the effect of glucocorticoids on collagen synthesis during fibrogenesis without the unwanted side effects of these steroids. Based on our previous studies on the molecular mechanisms by which glucocorticoids selectively decrease collagen synthesis, designed phosphorothioate oligodeoxynucleotides resistant to nuclease action will mimic the effects of glucocorticoids at the molecular, cellular, and in vivo levels of collagen synthesis. However, the glucocorticoids significantly inhibit noncollagen protein synthesis. Both the single-stranded and double-stranded oligodeoxynucleotide specifically decrease collagen synthesis without an inhibitory effect on noncollagen protein synthesis. In this review, we will specifically ask if TGF-beta-induced collagen synthesis is inhibited in cell culture and in vivo by using the double-stranded oligodeoxynucleotide decoys, will this inhibit fibrogenesis and ultimately scarring? PMID- 17727469 TI - Cellular and molecular pathology of HTS: basis for treatment. AB - Hypertrophic scar and keloids are fibroproliferative disorders of the skin which occur often unpredictably, following trauma and inflammation that compromise cosmesis and function and commonly recur following surgical attempts for improvement. Despite decades of research in these fibrotic conditions, current non-surgical methods of treatment are slow, inconvenient and often only partially effective. Fibroblasts from these conditions are activated to produce extracellular matrix proteins such as collagen I and III, proteoglycans such as versican and biglycan and growth factors, including transforming growth factor beta and insulin like growth factor I. However, more consistently these cells produce less remodeling enzymes including collagenase and other matrix metalloproteinases, as well as the small proteoglycan decorin which is important for normal collagen fibrillogenesis. Recently, the systemic response to injury appears to influence the local healing process whereby increases in Th2 and possibly Th3 cytokines such as IL-2, IL-4 and IL-10 and TGF-beta are present in the circulating lymphocytes in these fibrotic conditions. Finally, unique bone marrow derived cells including mesenchymal and endothelial stem cells as well as fibrocytes appear to traffic into healing wounds and influence the healing tissue. On this background, clinicians are faced with patients who require treatment and the pathophysiologic basis as currently understood is reviewed for a number of emerging modalities. PMID- 17727471 TI - The long drought: the dearth of public funding for headache research. PMID- 17727472 TI - Funding of headache research in Europe. AB - Migraine costs European Society 27 billion Euro per year. Other headaches may account for a similar amount. Given this enormous impact, the question arises as to whether the funding of research efforts in this field are sufficient. A recent European study called the Resource Allocation to Brain Research in Europe (RABRE) examined funding of brain research. Identified charities and Government agencies in Europe filled out a questionnaire regarding their funding of brain diseases. Industry spending was evaluated by three different previously validated methods. In the present report, detailed results are presented for migraine and other headaches. In 2004, migraine research was funded by nearly 315 million Euro . Of this, 308 million Euro was invested by the pharmaceutical industry, whereas public funding was estimated at 7 million Euro . No funding was identified for non-migraine headache disorders. Of the public spending, 714,000 Euro came from private foundations. There was a very large difference between different European countries in the funding of headache research. When public funding was compared with the cost of different brain disorders, migraine funding was in the middle range. This was due to relatively large industry funding. Compared with societal costs, migraine received the least public funds amongst all brain disorders, i.e. 0.025%. We conclude that migraine attracts reasonable interest from the pharmaceutical industry, but Governmental and charity funding is extremely low and no funding was identified for non-migraine headache disorders. Considering the huge economic impact of these disorders, public funding of research into migraine and other headaches should be greatly increased in the future. PMID- 17727473 TI - Biomarker-assisted diagnosis of ovarian, cervical and pulmonary small cell carcinomas: the role of TTF-1, WT-1 and HPV analysis. AB - AIMS: Small cell carcinoma of the ovary, hypercalcaemic-type (SCCOH) is morphologically similar to small cell carcinomas from other sites. The aims of this study were to (i) determine if a biomarker panel would distinguish small cell carcinomas of the ovary, cervix (SCCCx) and lung (SCCLu) and (ii) potentially determine the histogenesis of SCCOH. METHODS AND RESULTS: Nine ovarian small cell carcinomas (seven hypercalcaemic type; two pulmonary type), eight SCCCx and 22 SCCLu were immunostained for thyroid transcription factor (TTF)-1, WT-1, p16, cKIT and OCT3/4; a subset of cases were tested for human papillomavirus (HPV). WT-1 was diffusely positive in 6/7 SSCOH versus two of 33 other small cell carcinomas (P 0.6 in a reproducibility study: stromal cellularity increased in at least 50% compared with typical fibroadenoma, stromal overgrowth (x10 field with no epithelium), fragmentation and adipose tissue within stroma. CONCLUSIONS: This study describes features useful in the diagnosis of phyllodes tumour on core biopsy. Some core biopsy specimens from phyllodes tumours show features of fibroadenoma on core biopsy because of tumour heterogeneity. PMID- 17727477 TI - Distinct angiogenic and non-angiogenic growth patterns of lung metastases from renal cell carcinoma. AB - AIMS: We have recently evaluated a classification of non-small-cell lung cancer based upon the presence of an angiogenic or a non-angiogenic growth pattern. The aim of the present study was to test the hypothesis that lung metastases of clear cell renal cell carcinoma (RCC) can grow without eliciting angiogenesis and give rise to the same set of growth patterns. METHODS AND RESULTS: Tissue sections of 24 patients with lung metastases from clear cell RCC were analysed. Haematoxylin and eosin and reticulin staining were performed to evaluate growth pattern. Double-labelling with antibodies to CD34 and proliferating cell nuclear antigen (PCNA) was performed to determine the endothelial cell proliferation fraction (ECPF) and the microvessel density (MVD). Three growth patterns were observed. In the destructive growth pattern (54%), the architecture of the lung was not preserved. In the alveolar (33%) and interstitial growth patterns (13%), the normal lung parenchyma was preserved within the metastases. MVD was higher in the destructive than in the alveolar growth pattern (P = 0.009). ECPF was higher in the destructive (mean 31.1 +/- 22.7%, median 30.0) than in the alveolar growth pattern (mean 3.6 +/- 2.8%, median 3.2; P = 0.005). CONCLUSIONS: The present study demonstrates that highly angiogenic primary tumours can give rise to non angiogenic metastases. This type of metastasis may be resistant to antiangiogenic therapy. PMID- 17727476 TI - Lymphangiogenesis in myocardial remodelling after infarction. AB - AIMS: The lymphatic system is involved in fluid homeostasis of the cardiac interstitium, but lymphangiogenesis in myocardial remodelling has not previously been examined histopathologically. The aim was to investigate by D2-40 immunohistochemistry the sequential changes in lymphatic distribution in the process of myocardial remodelling after myocardial infarction (MI). METHODS AND RESULTS: Myocardial tissues in various phases of healing after MI were obtained from 40 autopsied hearts. D2-40+ lymphatic vessel density (LD) and CD34+ blood vessel density (BD) in the lesion were determined. BD decreased with advance of myocardial necrosis, subsequently increased at the early stage of granulation and thereafter decreased with the progression of scar formation. In contrast, lymphatic vessels were not detected in lesions with coagulation necrosis, and newly formed lymphatics first appeared in the early stages of granulation. A subsequent increase in LD was demonstrated in the late stages of granulation, and lymphatics remained up to the scar phase. Vascular endothelial growth factor-C was consistently expressed in viable cardiomyocytes around the lesion in all of these stages. CONCLUSION: In myocardial remodelling after MI, lymphangiogenesis lags behind blood vessel angiogenesis; newly formed lymphatics may be involved mainly in the maturation of fibrosis and scar formation through the drainage of excessive proteins and fluid. PMID- 17727478 TI - Identification of serosal invasion and extramural venous invasion on review of Dukes' stage B colonic carcinomas and correlation with survival. AB - AIMS: To determine whether serosal invasion (SI) and/or extramural venous invasion (VI) could be more frequently identified on review of Dukes' stage B colonic carcinoma resection specimens and whether the revised findings correlated with clinical outcome. METHODS AND RESULTS: The original histology slides from 82 patients with Dukes' stage B colonic carcinoma were reviewed specifically to identify tumours showing SI and/or VI. All tumours were initially reported to be negative for both pathological parameters. The selected cases included 35 patients who died of carcinoma within 5 years of surgery and 47 patients with a minimum of 5-years' postoperative survival. The review was blinded to the original histopathology reports and to clinical follow-up data. SI and/or VI were identified in 26 cases (32%). Fourteen of 18 patients with SI, 8/12 patients with VI and all four patients with both adverse histological features died of carcinoma. CONCLUSIONS: Review of routinely sampled and stained colonic carcinoma resection specimens increased the proportion of cases classified as positive for SI and/or VI. The revised assessment correlated with patient outcome. Reliable identification of these features may permit stratification of high-risk patients with Dukes' stage B colonic cancer who could benefit from adjuvant treatment. PMID- 17727479 TI - Prognostic significance of p53 gene mutations and protein overexpression in localized gastrointestinal stromal tumours. AB - AIMS: Mutation of c-kit is a relatively early event in the tumorigenesis of gastrointestinal stromal tumours (GISTs). The aim was to determine the prognostic significance of p53 alterations as an additional genetic change in GISTs. METHODS AND RESULTS: We reviewed 125 patients with localized GISTs subjected to complete resection between 1990 and 2002. Mutational analyses of c-kit exons 9, 11, 13 and 17, p53 exons 4-8 and immunohistochemistry for p53 protein were conducted using paraffin-embedded tissues. Alterations of p53 were observed in 50 patients (40.0%). Based on the National Institutes of Health's risk category, p53 alterations were noted more frequently in the higher risk categories (P = 0.041). With a median follow-up of 56.5 months (range: 2.3-126.8), 5-year relapse-free survival (RFS) rates were 61.7% without p53 alterations, compared with only 40.2% with p53 alterations (P = 0.009). Multivariate analysis indicated that p53 alterations comprised an independent, poor prognostic factor for RFS, in addition to c-kit mutations, large size, a high mitotic count and non-gastric primary sites. CONCLUSIONS: Alterations in p53 were more commonly observed in localized GISTs at higher risk of relapse. This suggests that they are significant as an independent, poor prognostic factor. PMID- 17727480 TI - Intravascular proliferation of reactive lymphoid blasts mimicking intravascular lymphoma--a diagnostic pitfall. PMID- 17727482 TI - Large cell neuroendocrine carcinoma of the uterine cervix exhibiting TTF1 immunoreactivity. PMID- 17727483 TI - NSAID-associated submucosal fibrous nodules of the small intestine. PMID- 17727484 TI - Cellular angiofibroma: another mesenchymal tumour with 13q14 involvement, suggesting a link with spindle cell lipoma and (extra)-mammary myofibroblastoma. PMID- 17727485 TI - Multifocal benign notochordal cell tumours. PMID- 17727486 TI - Chondroblastomas but not chondromyxoid fibromas express cytokeratins: an unusual presentation of a chondroblastoma in the metaphyseal cortex of the tibia. PMID- 17727487 TI - Kinetic topographical heterogeneity in follicular thyroid neoplasms and growth patterns. PMID- 17727488 TI - Co-secretion of testosterone and cortisol by a functional adrenocortical oncocytoma. PMID- 17727489 TI - Composite malignant pheochromocytoma with malignant peripheral nerve sheath tumour: a case with 28 years of tumour-bearing history. PMID- 17727491 TI - Meningiomas do not express CD117 (KIT). PMID- 17727490 TI - CT-guided, COBRA-FISH-assisted diagnosis of well-differentiated liposarcoma (inflammatory subtype) of the retroperitoneum. PMID- 17727492 TI - Mucinous bronchioloalveolar carcinoma of lung with a rhabdoid component--report of a case and review of the literature. PMID- 17727493 TI - Pleomorphic olfactory neuroblastoma (esthesioneuroblastoma): histopathological findings and clinical course. PMID- 17727499 TI - How far merit selection? Social stratification and the labour market. AB - The question of how societies allocate occupational positions and subsequent rewards has long been of interest to sociologists. According to one influential theory, the needs of modern industrial societies and economies demand that high level and functionally important occupational positions are allocated according to meritocratic principles. I argue that, ultimately, employers get the final say about which characteristics are rewarded in the labour market. In order to examine which skills and attributes are required by employers for particular occupations I analyse data drawn from a content analysis of c.5000 British newspaper job advertisements. The results show that both merit and non-merit characteristics are requested by employers in job advertisements, even for occupations falling within the higher classes. I also find evidence that employers have similar requirements for similar occupations, cross-cutting class boundaries. PMID- 17727498 TI - Beck, individualization and the death of class: a critique. AB - Ulrich Beck has argued that the changing logic of distribution and, more importantly, the 'individualization' of social processes in reflexive modernity have killed off the concept of social class and rendered the analysis of its effects a flawed endeavour. The present paper takes issue with this perspective by exposing its key weaknesses, namely its ambivalence and contradiction over what exactly constitutes individualization and the extent to which it has really displaced class, its inconsistent and caricaturized description of what actually constitutes class, its erroneous and unsatisfactory depiction of class analysis, and its self-defeating reasoning on the motors of individualization. The intention is not to conservatively deny that social change is occurring nor to advocate any particular model of class, but only to illustrate the aporias of Beck's position with the aim of vindicating the enterprise of class analysis. PMID- 17727500 TI - Cultural capital or relative risk aversion? Two mechanisms for educational inequality compared. AB - In this paper we empirically examined two explanatory mechanisms for educational inequality: cultural reproduction and relative risk aversion, using survey data taken from secondary school pupils in Amsterdam. Cultural reproduction theory seeks to explain class variations in schooling by cultural differences between social classes. Relative risk aversion theory argues that educational inequalities can be understood by between-class variation in the necessity of pursuing education at branching points in order to avoid downward mobility. We showed that class variations in early demonstrated ability are for a substantial part cultural: cultural capital - measured by parental involvement in highbrow culture - affected school performance at the primary and secondary level. However, relative risk aversion - operationalized by being concerned with downward mobility - strongly affects schooling ambitions, whereas cultural capital had no effect. Thus, we conclude that 'primary effects' of social origin on schooling outcomes are manifested through cultural capital and not through relative risk aversion (in addition to other potential sources of class variations such as genetics). Relative risk aversion, and not cultural capital, affects schooling ambitions, which is relevant for our understanding of secondary effects. PMID- 17727502 TI - Beyond the binge in 'booze Britain': market-led liminalization and the spectacle of binge drinking. AB - The contemporary night-time economy has transformed British town centres into liminal spaces where transgression does not subvert normative space, but establishes public drunkenness as integral to a negotiated order. The focus of this paper is the wider dialectic surrounding contemporary 'binge drinking', and in particular the relationship between aesthetic processes aimed at encouraging alcohol-related excitement and excess, and those that seek to exert a measure of rational control over the drink 'problem'. It is the logic of the market that informs governmental policy on alcohol, and the binge drinker is central to the spectacle of the night-time economy as a form of self gratification which also embodies forms of repression. PMID- 17727501 TI - The Pinochet case: cosmopolitanism and intermestic human rights. AB - This article explores the Pinochet case, widely heralded as a landmark, as a case of 'intermestic' human rights that raises difficult normative and empirical questions concerning cosmopolitan justice. The article is a contribution to the sociology of human rights from the perspective of methodological cosmopolitanism, developing conceptual tools and methods to study how cosmopolitanizing state institutions and cultural norms are inter-related. The argument is made that in order to understand issues of cosmopolitan justice, sociologists must give more consideration to political culture. PMID- 17727503 TI - Sociology, ethics, and the priority of the particular: learning from a case study of genetic deliberations. AB - There are growing debates about the relationship between the two disciplines of sociology and ethics, particularly as they each become increasingly involved in research and policy formation on the life sciences, especially genetics. Much of this debate has been highly abstract, often stipulating the seemingly different character of the two disciplines and speculating on their theoretical potential- or lack thereof--for future collaborative work. This article uses an existing collaboration between a sociologist and an ethicist, on a study of participation in genetic databases, to explore some of the challenges, for both disciplines, of working together. Building upon this case study, we examine the suggestion that the Aristotelian concept of 'phronesis' provides the grounds for establishing one possible theoretical framework with which the disciplines can be bridged. Further exploration of this approach leads to suggestions for ways of thinking about the apparently fundamental divides between the disciplines and for ways of adding to notions of a 'public sociology'. PMID- 17727504 TI - Foucault's void. PMID- 17727524 TI - Abstracts of the 4th World Congress - World Institute of Pain, September 25-28, 2007. PMID- 17727525 TI - Factors inhibiting assessment of students' professional behaviour in the tutorial group during problem-based learning. AB - CONTEXT: We addressed the assessment of professional behaviour in tutorial groups by investigating students' perceptions of the frequency and impact of critical incidents that impede this assessment and 5 factors underlying these critical incidents. METHODS: A questionnaire asking students to rate the frequency and impact of 40 critical incidents relating to effective assessment of professional behaviour on a 5-point Likert scale was developed and sent to all undergraduate medical students in Years 2-4 of a 6-year undergraduate curriculum. RESULTS: The response rate was 70% (n = 393). Important factors underlying critical incidents are: lack of effective interaction; lack of thoroughness; tutors' failure to confront students with unprofessional behaviour; lack of effort to find solutions, and lack of student motivation. Confirmatory factor analysis showed a good model fit. Because the relationship between frequency of occurrence and degree of impediment varies, the best information about the true impact of critical incidents and the underlying factors is provided by the product of frequency and degree of impediment. Frequency of occurrence remains stable and degree of impediment increases in Years 2-4. CONCLUSIONS: The results of this study can be used to design and improve faculty development programmes aimed at improving assessment of professional behaviour. Training programmes should motivate tutors by providing background information as to why and how sound assessment of professional behaviour is to be performed and encourage tutors to confront students with and discuss all aspects of professional behaviour, as well as provide appropriate feedback. PMID- 17727526 TI - Does feedback matter? Practice-based learning for medical students after a multi institutional clinical performance examination. AB - CONTEXT: Achieving competence in 'practice-based learning' implies that doctors can accurately self- assess their clinical skills to identify behaviours that need improvement. This study examines the impact of receiving feedback via performance benchmarks on medical students' self-assessment after a clinical performance examination (CPX). METHODS: The authors developed a practice-based learning exercise at 3 institutions following a required 8-station CPX for medical students at the end of Year 3. Standardised patients (SPs) scored students after each station using checklists developed by experts. Students assessed their own performance immediately after the CPX (Phase 1). One month later, students watched their videotaped performance and reassessed (Phase 2). Some students received performance benchmarks (their scores, plus normative class data) before the video review. Pearson's correlations between self-ratings and SP ratings were calculated for overall performance and specific skill areas (history taking, physical examination, doctor-patient communication) for Phase 1 and Phase 2. The 2 correlations were then compared for each student group (i.e. those who received and those who did not receive feedback). RESULTS: A total of 280 students completed both study phases. Mean CPX scores ranged from 51% to 71% of items correct overall and for each skill area. Phase 1 self-assessment correlated weakly with SP ratings of student performance (r = 0.01-0.16). Without feedback, Phase 2 correlations remained weak (r = 0.13-0.18; n = 109). With feedback, Phase 2 correlations improved significantly (r = 0.26-0.47; n = 171). Low-performing students showed the greatest improvement after receiving feedback. CONCLUSIONS: The accuracy of student self-assessment was poor after a CPX, but improved significantly with performance feedback (scores and benchmarks). Videotape review alone (without feedback) did not improve self-assessment accuracy. Practice-based learning exercises that incorporate feedback to medical students hold promise to improve self-assessment skills. PMID- 17727527 TI - Reliability of peer and self-assessment scores compared with trainers' scores following third molar surgery. AB - CONTEXT: It is sometimes claimed that self-assessment is inaccurate and that clinicians over-rate their performance. There is a need to find out why this should be. Is poor self-assessment caused by some clinicians' inability to accurately judge performance? Or does over-scoring result from a desire to convey a more favourable impression? Peer assessment is widely advocated and is said to be of benefit to both assessor and assessee. METHODS: In this study, we wanted to see if postgraduates were able to peer-assess and if this form of assessment was more reliable than self-assessment when compared with assessment by a trainer. We used checklist and global rating scales to evaluate surgical skills in removing a mandibular third molar tooth. RESULTS: There was no statistically significant difference between peer-assessed and trainer-assessed scores. We found that, on average, peer assessment (especially global rating scales) reflected trainer scores more accurately than self-assessment of surgical skills. Self-assessment scores were significantly higher on average than those given in peer assessment. DISCUSSION: Although peers and trainee surgeons came from the same group, the surgeons were more likely to over-score when measuring their own performances. The greatest variability (and over-scoring) between assessor and trainee surgeon appeared to occur in those with lower mean scores. Formative peer assessment may be a useful and less stressful mechanism for encouraging reflection. PMID- 17727528 TI - Simulating the longitudinal doctor-patient relationship: experiences of simulated patients in successive consultations. AB - CONTEXT: The use of simulated patients (SPs) in teaching communication and practical skills at medical schools is mostly limited to single-case use: a student has 1 consultation with an SP and receives feedback afterwards. Very little literature is available that describes consecutive consultations between the same student and SP. In this study, we explored the experiences of SPs in a new, longitudinal SP programme in which SPs met the same Year 3 students ('GP') in 4 consecutive consultations during the year. The SPs suffered from a chronic disease in their patient roles. METHODS: Four focus group discussions were conducted with 23 SPs (8 men, 15 women; average age 60.9 years) who had performed in the new programme. Discussions were semi-structured and followed a pre established interview guide. Data were categorised by 3 independent raters. RESULTS: The SPs described the development of a more familiar relationship with students under the new programme, compared with single-case consultations. They developed specific expectations of students' performances. The SPs enjoyed participating in the programme and felt it was more realistic than single-case consultations. Feedback changed and became more detailed as SPs were able to compare consultations; students' response to feedback could be experienced during the next consultation. DISCUSSION: Practising the development of a realistic, longitudinal doctor-patient relationship may help prepare students for real practice. Longitudinal feedback is now possible; it may be of higher quality and of benefit to SPs as well. These findings suggest new possibilities for SP-based education and research. Future studies should focus on quantitative analysis and students' perspectives. PMID- 17727529 TI - The effect of candidate familiarity on examiner OSCE scores. AB - CONTEXT: Although examiners are a large source of variability in the objective structured clinical examination (OSCE), the exact causes of examiner variance remain understudied. OBJECTIVE: This study aimed to determine whether examiner familiarity with candidates influences candidate scores. METHODS: A total of 24 candidates from 4 neonatal-perinatal training programmes participated in a 10 station OSCE. Sixteen trainees and 7 examiners came from a single centre (site A) and 8 candidates and 5 examiners came from the other 3 centres. Examiners completed station-specific binary checklists and an overall global rating; standardised patients (SPs) and standardised health professionals (SHPs) completed 4 process ratings and the overall rating. A fixed-effect, 2-way analysis of variance was performed to ascertain whether there was interaction between examiner site and candidate site. RESULTS: Interstation Cronbach's alpha was 0.80 for the examiner checklist, 0.88 for the examiner global rating and 0.88 for the SP or SHP global rating. Although the checklist scores awarded by site A examiners were significantly higher than those awarded by non-site A examiners, there was no significant interaction between examiner and candidate site (P = 0.124). Similarly, the interaction between examiner and candidate site for the global rating was not significant (P = 0.207). Global ratings awarded by SPs and SHPs were also higher in stations where site A faculty examined site A candidates, suggesting the observed differences may have been related to performance. CONCLUSIONS: Results from this small dataset suggest that examiner familiarity with candidates does not influence how examiners score candidates, confirming the objective nature of the OSCE. Confirmation with a larger study is required. PMID- 17727530 TI - Instructional methods and cognitive and learning styles in web-based learning: report of two randomised trials. AB - CONTEXT: Adapting web-based (WB) instruction to learners' individual differences may enhance learning. Objectives This study aimed to investigate aptitude treatment interactions between learning and cognitive styles and WB instructional methods. METHODS: We carried out a factorial, randomised, controlled, crossover, post-test-only trial involving 89 internal medicine residents, family practice residents and medical students at 2 US medical schools. Parallel versions of a WB course in complementary medicine used either active or reflective questions and different end-of-module review activities ('create and study a summary table' or 'study an instructor-created table'). Participants were matched or mismatched to question type based on active or reflective learning style. Participants used each review activity for 1 course module (crossover design). Outcome measurements included the Index of Learning Styles, the Cognitive Styles Analysis test, knowledge post-test, course rating and preference. RESULTS: Post-test scores were similar for matched (mean +/- standard error of the mean 77.4 +/- 1.7) and mismatched (76.9 +/- 1.7) learners (95% confidence interval [CI] for difference - 4.3 to 5.2l, P = 0.84), as were course ratings (P = 0.16). Post-test scores did not differ between active-type questions (77.1 +/- 2.1) and reflective-type questions (77.2 +/- 1.4; P = 0.97). Post-test scores correlated with course ratings (r = 0.45). There was no difference in post-test subscores for modules completed using the 'construct table' format (78.1 +/- 1.4) or the 'table provided' format (76.1 +/- 1.4; CI - 1.1 to 5.0, P = 0.21), and wholist and analytic styles had no interaction (P = 0.75) or main effect (P = 0.18). There was no association between activity preference and wholist or analytic scores (P = 0.37). CONCLUSIONS: Cognitive and learning styles had no apparent influence on learning outcomes. There were no differences in outcome between these instructional methods. PMID- 17727532 TI - Trials in medical education: fret less about contamination and more about statistical power. PMID- 17727531 TI - Women in the UK academic medicine workforce. AB - OBJECTIVES: This study aimed to compare data on the employment profiles (such as grade, place of work, etc.) of male and female clinical academics. METHODS: We carried out a comparative review of workforce data within academic medicine for 2004 and 2005, pertaining to the workforce in all specialties in UK medical schools. RESULTS: We identified 3255 and 3365 lecturers, senior lecturers, readers and professors in 2004 and 2005, respectively, of whom 21% were women. In 2004 and 2005, 12% and 11%, respectively, of 1157 and 1364 UK medical professors were women. The number of women filling such positions in individual schools ranged from 0% to 33% across schools. The total numbers of women post-holders and their full-time equivalents were similar, indicating that the majority of posts were full-time. CONCLUSIONS: In England only 1 in 10 medical clinical professors are women. At the onset of the study period, 6 medical schools employed no female professors, with a consequent lack of female role models at these institutions. Large variations between schools suggest that some workforce practices may be detrimental to women's academic careers. PMID- 17727533 TI - Integrating basic laboratory skills and clinical practice. PMID- 17727534 TI - Do newly qualified doctors use the knowledge and skills they learned as medical undergraduates? PMID- 17727535 TI - How literature and popular movies can help in medical education: applications for teaching the doctor-patient relationship. PMID- 17727536 TI - Mentorship in academic medicine. PMID- 17727537 TI - What do parents think about their children being involved in medical education? PMID- 17727540 TI - Living with a body in pain -- between acceptance and denial. AB - The aetiology of nonspecific musculoskeletal pain is considered to be multi factorial. Long-standing pain not only has a negative impact on the individual's general health but also changes the individual's experience of him/her self and his/her world. The aim of this study was to describe how individuals with long standing musculoskeletal pain, in a bodily existential perspective, relate to their aching body. Semi-structured interviews with 20 patients were analysed using mainly a phenomenological-hermeneutic method. From the analysis, four main categories reflect the meaning contents of the interviews: the body as an aspect of identity; body reliance; body awareness; ways of understanding pain. From these categories, four distinct typologies were inferred: surrendering to ones fate; accepting by an active process of change; balancing between hope and resignation; rejecting the body. The result indicates that patients with long standing pain are to be found along a spectrum from accepting to rejecting the aching body. Body awareness and body reliance seem to have importance in the process of acceptance of the body as well as life situation as a whole, which we regard as interesting hypotheses for further inquiry. PMID- 17727542 TI - Fear of humiliation inhibits women's care-seeking behaviour for long-term urinary incontinence. AB - Most women with urinary incontinence (UI) do not seek professional help. Women's experiences of their behaviour when seeking care for incontinence are important to improve understanding by nurses and encourage as well as enable women to seek help. The aim of this study was to illuminate the meaning of women's lived experiences of their behaviour when seeking care for long-term UI. Thirteen women were interviewed (range 37-52 years) who had not sought professional help for incontinence. A phenomenological hermeneutic method was used to analyse and interpret the interview texts. Three themes evolved from data: being in an affected situation, having personal beliefs about seeking care and having desired expectations about care. Being in an affected situation, means that the women were negatively affected by their long-term incontinence. Living with shame, altered sexual relationships and a need for distancing have negatively influenced their care-seeking behaviour (CSB). Having personal beliefs about seeking care means that the women had their own beliefs regarding morally acceptable behaviour for seeking care because of incontinence. This led to a toning down of their problem and a minimization of the problem associated with incontinence as it was considered to be a normal consequence of pregnancy and childbirth. Having desired expectations about care means that the women had opinions relevant to the care and felt being asked about incontinence and an understanding atmosphere should be included. The conclusion is that fear of humiliation inhibited women from seeking care for long-term UI. The findings suggest that nurses should be precise when asking about women's experiences of UI because otherwise they do not bring it up. Additionally, CSB can help nurses to explain the experience and enable women to seek help for this manageable condition. PMID- 17727541 TI - The experience of women with advanced chronic obstructive pulmonary disease of repeatedly relapsing to smoking. AB - Living with chronic obstructive pulmonary disease (COPD) a smoking-related disease and repeatedly relapsing to smoking is a complicated health problem, particularly for people expected to be at the peak of their productivity in life. As the prevalence of COPD among women is on the rise devoted attentiveness must be given to women's smoking. The purpose of this study is to illuminate the experience of women with COPD of repeatedly relapsing to smoking. The study draws on interpretive phenomenology. Seven women, aged 47-65 years, selected out of convenience, were interviewed twice, shortly after being hospitalized for an exacerbation of the disease. Data were analysed into themes emphasizing commonalities and differences in the lived experience. Results illustrate the intricacies between the lung disease, which controls life of participants on a very fundamental level and smoking cigarettes, which only augments the disease. Six not mutually exclusive themes emerged with one, being caught in a spider web, overarching. Other themes were: circumstances of the relapses, shame, the excuse, ambivalence and incomplete attempts to quit. The capacity of the women participating in this study to refrain from smoking was limited and they vacillated between wanting and not wanting to stop. This suggests that for women in similar situations an exhaustive and long-term nursing care is necessary for them to be able to come to terms with what they really aspire to and to stay with that decision. PMID- 17727543 TI - Patient participation in nursing care from a patient perspective: a Grounded Theory study. AB - the study's rationale: Patients' active participation in their own care is expected to contribute to increased motivation to improve their own condition, better treatment results and greater satisfaction with received care. Knowledge of patients' understanding of participation is of great importance for nurses in their efforts to meet patient expectations and for quality of nursing care. AIM: The aim was to explore the meaning of patient participation in nursing care from a patient point of view. METHODOLOGICAL DESIGN AND JUSTIFICATION: Six tape recorded focus group interviews with 26 Swedish informants described opinions on and experiences of patient participation. The informants consisted of patients in somatic inpatient care as well as discharged patients from such a setting. The Grounded Theory method was used and the data were analysed using constant comparative analysis. ETHICAL ISSUES AND APPROVAL: The ethics of scientific work was followed. Each study participant gave informed consent after verbal and written information. The Ethics Committee of Goteborg University approved the study. FINDINGS: The patients emphasised the importance of collaboration to improve participation. The core category, Insight through consideration, was generated from four inter-related categories: (i) Obliging atmosphere; (ii) Emotional response; (iii) Concordance; and (iv) Rights and their 15 subcategories. CONCLUSIONS: The meaning structures of patient participation in nursing care revealed from a patient point of view, seemed to mainly consist of not only external factors presented by the institutions -- by the professionals - but also internal patient factors. The patients' view of participation should be considered to a greater degree in nursing practice and education, as should also further development of nursing care policy programmes, evaluation and quality assurance criteria. For further development, studies are needed in similar and other settings. PMID- 17727544 TI - Dimensions of health-related lifestyle in young adulthood: results from a national population survey. AB - AIM: This study assessed the underlying structure of health-related behaviours among young adults in Iceland. A number of individual behaviours were considered, including both positive and negative health-related behaviours. A central question was whether distinct underlying health-related lifestyles can be identified in this age group. METHOD: The study was based on the data from a national health survey entitled 'Health and Living Conditions in Iceland'. The original survey comprised a random sample of 18-75 year olds drawn from the National Register (response rate 69%). The current study used a subsample from the survey, consisting of young adults, age: 18-24 (N = 348). A total of 37 variables pertaining to health-related behaviour were analysed. The 37 variables were factor-analysed using principal component (PC) factor analysis. RESULTS: The PC analysis yielded four underlying health lifestyle dimensions: (i) physical activity; (ii) unhealthy diet; (iii) substance use; and (iv) healthy diet. The four factors explained 35.3% of the total item variance. The mean Cronbach's alpha for the four factors was 0.69. Correlations between factors were generally weak. CONCLUSION: Distinct health-related lifestyle dimensions underlie the numerous health-related behaviours that young adults engage in. The analysis of positive and negative lifestyle dimensions helps identify vulnerable young adults disproportionally involved in unfavourable patterns of health-related behaviour. Weak factor correlations and high unexplained item variance suggests that individual health-related behaviours need consideration, albeit within a larger framework acknowledging interconnected and sometimes inconsistent behaviours. PMID- 17727545 TI - Adaptation and resiliency in Swedish families. AB - A longitudinal research project began in 1993 of Norwegian, Swedish and American mothers' perception of her family's dynamics and adaptation during childbearing and childrearing. Results indicated that Swedish mothers adapted better than other mothers. In 2003, a mixed design study was conducted with original Swedish mothers that aimed to describe the experience of motherhood, the meaning mothers attached to events in their lives that made adaptation necessary, and ways in which they achieved adaptation. Fourteen mothers completed quantitative instruments and 13 of those mothers were interviewed. Audiotaped interviews were transcribed and analysed for themes using a protocol based on a model of family resiliency. Quantitative findings revealed statistically significant findings in areas of children, mother's work outside the home and families in which a major illness had occurred. Qualitative findings revealed that protective factors far outweighed vulnerability and risk factors. Mothers' satisfaction with life manifested itself in love of home, contentment with employment, fulfillment from an active and healthy life and support from a society that provides a wide range of social benefits for the family. Vulnerability occurred primarily when mothers were tired, lacked personal time or someone in the family was experiencing a serious illness. Results of this study enhance the scholarly scientific knowledge about the uniqueness of Swedish mothers, and increased understanding of family dynamics and adaptation. Many of the findings relate in some way to overall social benefits and supports available for families. PMID- 17727546 TI - Being a close relative of a person with severe, chronic heart failure in palliative advanced home care -- a comfort but also a strain. AB - Within previous research on family care of terminally ill people, studies have only rarely been carried out concerning heart failure care. This study aims to illuminate meanings of being a close relative of a person with severe, chronic heart failure (CHF) in palliative advanced home care (PAHC). Narrative interviews were conducted with three close relatives, tape-recorded, transcribed verbatim and a phenomenological-hermeneutic method was used to interpret the text. Meanings of being a close relative is to follow the life-threatening ups and downs, the person with CHF is going through. This means being on primary call, always on standby to mediate security and pleasure. In the deepest downs it is also to call for the back-up call i.e. the PAHC team, trusting their ability to show up on time to alleviate in the worst downs i.e. ease suffering. This study reveals that to be the close relative that the ill person is dependent on 24 hours a day is both a comfort and a strain. PMID- 17727547 TI - Admiral nursing and the family care of a parent with dementia: using autobiographical narrative as grounding for negotiated clinical practice and decision-making. AB - BACKGROUND: Providing family care at home for a person with a long-established diagnosis of dementia has been recognized for some time as a multifaceted and complex phenomenon where care roles alter during the course of the condition. Presently, the nursing response to meeting such need is currently poorly defined and documented in the literature and depends more upon descriptive illustrations of practice efficacy rather than any evaluated system of knowledge and skills transfer or framework utilization. AIM: The aim of the study was to capture an autobiographical account of a family carer's (Kath, co-author) journey through the experience of her mother's dementia and the reflexive dialogue and shared care planning that ensued with the Admiral Nurse (Susan, co-author). DESIGN: Kath's narrative was captured using practitioner-research principles and 10 interview contacts; the autobiography was then used as the basis for therapeutic and clinical work, as reported and jointly negotiated between Kath and Susan. RESULTS: The findings demonstrate the importance of constructing care from an autobiographical perspective and integrating lay knowledge within an overall professional response to family/carer need in dementia caregiving situations. The negotiated clinical response to Kath's grief process (the death of Kath's father, the main carer support to her mother with dementia) and Kath's subsequent adaptation process is illustrated through a shared sessional plan and agreed measures of effective care. CONCLUSION: Integrating narrative approaches into care practice demonstrates important new ways of working alongside families of people with dementia to help develop negotiated, transparent and shared systems of care. PMID- 17727548 TI - Culturally congruent care for older people: Finnish care in Sweden. AB - An increasing number of older people belong to minority and immigrant groups. This calls for new models on the subject of how to provide culturally adjusted care for these populations. The aim of this study is to describe how cultural congruency is used in care for older Finnish immigrants in order to promote their well-being. The study was conducted with an ethnographic design, based on participant observations and interviews among residents, staff, and visitors in the Finnish Home in Sweden. In the core of the cultural congruency is the use of the Finnish language, and the fact that both residents and staff have Finnish backgrounds. In addition to this, Finnish customs and celebrations, popular culture, and topics of discussion, are actively used in order to create a common ground for communication and shared understanding of the individual person. Cultural congruency, based on the residents' mother language, shared ethnic background with staff, and shared customs creates a common ground for communication and an understanding. This enables caring relationships, which, in turn, increases the residents' well-being. PMID- 17727549 TI - The professional development of nursing through different aspects of the caring practices of nurses: nursing the patient person in a geriatric assessment unit. AB - The caring component of nursing practice has become an increasingly visible activity of nursing. Consequently, a growing amount of research has explored the role caring plays in nurse practice. Research often explores the activities of caring or its moral agenda, rather than motivation. This study broadens the discussion about nurses and caring practice by examining nurses approaches to different aspects of the caring practices of nurses for the aged in a Geriatric Assessment Unit (GAU). Data collection involved semi-structured interviews and participant observation within the GAU. Four categories of themes emerged as different aspects of the caring practices of nurses. Three fit within the professional development of nursing: physical caring, negotiative caring and relational caring. A fourth, motivated caring, however, provides an additional aspect of caring located within and beyond professional development. PMID- 17727550 TI - Older adults experiences of rehabilitation in acute health care. AB - Rehabilitation is a key component of nursing and allied healthcare professionals' roles in most health and social care settings. This paper reports on stage 2 of an action research project to ascertain older adult's experience of rehabilitation. Twenty postdischarge interviews were conducted and the interview transcripts were analysed using thematic content analysis. All older adults discharged from an acute older acute rehabilitation ward to their own homes in the community were eligible to participate. The only exclusion criterion was older adults who were thought to be unable to give consent to participate by the nurse in charge and the researcher. Whilst 92 older adults were eligible to participate in this research study, only 20 were interviewed. The findings from this study suggest that older adults valued communication with health professionals but were aware of their time constraints that hindered communication. This study suggests that both nurses and allied health professionals are not actively providing rehabilitative services to promote health and well-being, which contradicts the focus of active ageing. Furthermore, there was evidence of unmet needs on discharge, and older adults unable to recall the professions that were involved in their interventions and the rationale for therapy input. It is suggested that further research is needed to explore the effectiveness of allied health rehabilitation in the acute setting. This study highlights the need for further research into older adults' perceptions of the rehabilitation process in the acute setting. PMID- 17727551 TI - Despite shattered expectations a willingness to care for elders remains with education and clinical supervision. AB - The aim was to describe nursing home (NH) caregivers' work experiences while receiving education and clinical supervision for 2 years. Working in elder care seems to be losing its attraction especially with organizational changes, cutbacks and changes in work place conditions. Clinical supervision has been reported to increase job satisfaction and creativity. Semi-structured interviews from caregivers working at an NH in Sweden were conducted, at the start and again at 12 and 24 months. At about 12 months the caregivers were informed of planned cutbacks. Content analysis was the method used to analyse the interviews from seven caregivers who participated throughout the entire period. Findings show that the value of a caring milieu was one category generated by the subcategories: experiences related to work activities and changes, and experiences related to relationships. The value of knowledge was the other category that was influenced by the experiences related to the different backgrounds and the experiences related to increased knowledge gained from the support through education and clinical supervision. The categories contained positive as well as negative influences on care. The initial focus on practical duties associated with the opening of the NH shifted towards caregiver activities with the elders they spoke warmly about. After 2 years the caregivers' willingness to care continued despite their disappointment in the worsened working conditions. The main theme that resulted was: Despite shattered expectations a willingness to care for elders remained. Continued education and clinical supervision seems to be one factor behind the retained willingness. These findings demonstrate that support and caregiver involvement in educational programmes are important during times of change and when disappointments arise in the workplace. PMID- 17727552 TI - Assessing patient's care requirements: a comparison of instruments. AB - The purpose of this study was to compare two patient classification instruments developed in different countries, Perroca's (Brazil) and the Beakta (Sweden) systems and to investigate if both instruments equally assess patients' care requirements. The survey sample comprised 85 patients from a university hospital in southeast Sweden. Statistical analysis used Spearman's correlation and Kappa. The Spearman's correlation coefficient for total scores and classifications were 0.83 and 0.80, respectively (P-value < 0.01). The level of agreement between the instruments related to the different care categories pointed to an overall kw of 0.60 (95% CI: 0.50-0.71). The findings indicate a high degree of association between the total scores and patient classification assessment using the Beakta and Perroca systems and also a moderate level of agreement between the two instruments in the different care categories. There are few surveys that compare classification instruments between countries making it difficult to know to what extent cultural differences influence measurement approaches. PMID- 17727553 TI - Development of an instrument to test the middle-range theory for the self-care of home-dwelling elderly. AB - PURPOSE: This paper describes the process of developing an instrument to test the middle-range nursing theory for the self-care of home-dwelling elderly. BACKGROUND: Instrument development is a multiphase process, during which the researcher tests the reliability and validity of the instrument with various data and modifies it based on the test results. The aim of the study was to develop an instrument to test a theory, but also to be able to use it later in clinical settings to evaluate the self-care of home-dwelling elderly and factors associated with it. METHODS: The instrument development was done in four phases. At the first phase, the initial version was created on the basis of the theory. At the second phase, two home-dwelling elders were pilot-interviewed, and 20 elders completed the structured questionnaire and commented upon its ease of use. The results were used to develop the second version of the instrument. At the third phase, the second version of the instrument was used to collect data from home-dwelling elders aged 75 or more from different parts of Finland (n = 200). Face validity, exploratory factor analyses, correlation coefficients and Cronbach's alpha were used to test and further develop the instrument. At the fourth phase, the content validity of the third version was assessed by three home-dwelling elders. RESULTS: The agreement between the elders and the researchers about the contents of the instrument was acceptable, and exploratory factor analyses verified quite well the structure of the theory. Based on the Cronbach's alpha values (0.49-0.90), the internal consistency of the instrument was fairly good. CONCLUSION: The results provide sufficient evidence of the validity and reliability of the final version of the instrument, which has nine background questions and 82 items to measure the self-care of home-dwelling elderly and factors associated with it. PMID- 17727554 TI - Demand-oriented and demand-driven health care: the development of a typology. AB - In most European countries, there is an increasing demand for demand-oriented and demand-driven approaches in the development of health care policy and the organization of health care services. Both approaches, in which the main focus is on 'the demand', are seen as counterparts of the supply-oriented approach, that has 'the supply' as point of departure. However, there is much confusion about the definition of the concepts. To identify the different views, and to examine to what extent there is consensus in the Netherlands about the concepts of demand orientation and demand-driven care, a Delphi study was done among 26 experts; scientists, health care insurance companies, health care suppliers, the government, independent advisory bodies and client interest groups. The study resulted in a typology. The similarities and differences between the two concepts were demonstrated in five dimensions; responsibility, control, need determination, formal embedment of vision in organization and choice. Furthermore, the typology was used to identify existing types of services as being either demand-oriented or demand-driven services. The typology provides an understanding of the similarities and differences between the two concepts, and appears to be a useful tool in identifying services to the extent that they are demand oriented or demand driven. PMID- 17727555 TI - Myeloproliferative disorders: a time of new definitions. Outflow from New Horizons in Haematology Meeting, 9-10 March 2007. PMID- 17727556 TI - Advances in the understanding and management of myeloproliferative disorders. PMID- 17727557 TI - Update on the impact of the JAK2 mutation on signalling pathways in myeloproliferative disorders. PMID- 17727558 TI - Phenotype and genotype in the myeloproliferative disorders. PMID- 17727559 TI - Myelofibrosis: biology and treatment options. PMID- 17727560 TI - Unanswered questions in polycythaemia vera. PMID- 17727561 TI - Evolving management of essential thrombocythaemia. PMID- 17727562 TI - New consensus: a unified definition of clinical resistance and/or intolerance to hydroxyurea in essential thrombocythaemia. PMID- 17727563 TI - Essential thrombocythaemia treatment options: addressing patient-specific needs. PMID- 17727564 TI - Implications of the consensus definition of clinical resistance and intolerance to hydroxyurea for clinical practice. PMID- 17727565 TI - Options in the management of essential thrombocythaemia. PMID- 17727566 TI - Practical approach to treating essential thrombocythaemia: case studies. PMID- 17727567 TI - Malaria-specific antibody responses and parasite persistence after infection of mice with Plasmodium chabaudi chabaudi. AB - While it is known that antibodies are critical for clearance of malaria infections, it is not clear whether adequate antibody responses are maintained and what effect chronic infection has on this response. Here we show that mice with low-grade chronic primary infections of Plasmodium chabaudi or infections very recently eliminated have reduced second infections when compared with the second infection of parasite-free mice. We also show that parasite-specific antibody responses induced by infection of mice with Plasmodium chabaudi contain both short- and long-lived components as well as memory B cells responsible for a faster antibody response during re-infection. Furthermore, parasite-specific antibodies to the C-terminal fragment of merozoite surface protein-1 (MSP-1) undergo avidity maturation. However, antibodies with both low and high avidity persist throughout infection and after re-infection, suggesting repeated rounds of activation and maturation of memory B cells. Neither the avidity profile of the antibody response, nor its maintenance is affected by persisting live parasites. Therefore, differences in parasitemia in re-infection cannot be explained solely by higher levels of antibody or greater affinity maturation of malaria-specific antibodies. These data suggest that there may be an antibody independent component to the early control of secondary infections in mice that are chronically infected. PMID- 17727568 TI - GRA7 provides protective immunity in cocktail DNA vaccines against Toxoplasma gondii. AB - In a previous study, single-gene vaccination with GRA1, GRA7 or ROP2 was shown to elicit partial protection against Toxoplasma gondii. In this study, the contribution of each antigen in the evoked humoral and cellular immune responses was evaluated after vaccination with plasmid mixtures containing GRA1, GRA7 and ROP2. Cocktail DNA vaccinated mice developed high antibody titers against the antigens from two-gene DNA vaccine cocktails, but lower titres when immunized with the three-gene cocktail. High numbers of IFN-gamma secreting splenocytes were generated predominantly against GRA7. Brain cyst burden was reduced by 81% in mice vaccinated with the three-gene mixture and they were completely protected against acute toxoplasmosis. Similar high levels of brain cyst reductions were obtained after vaccination with cocktails composed of GRA1 and GRA7 (89% reduction), or GRA7 and ROP2 (79% reduction), but not with the cocktail composed of GRA1 and ROP2. In low dose single-gene vaccinations, IFN-gamma and strong protection could only be elicited by GRA7. Hence, the presence of GRA7 in the DNA vaccine formulation was important for optimal protection and this was correlated with GRA7-specific IFN-gamma production. We propose GRA7 as a main component in cocktail DNA vaccines for vaccination against T. gondii. PMID- 17727569 TI - Filaria/Wolbachia activation of dendritic cells and development of Th1-associated responses is dependent on Toll-like receptor 2 in a mouse model of ocular onchocerciasis (river blindness). AB - Toll-like receptors (TLRs) regulate dendritic cell function and activate signals that mediate the nature of the adaptive immune response. The current study examined the role of TLRs in dendritic cell activation and in regulating T cell and antibody responses to antigens from the filarial parasites Onchocerca volvulus and Brugia malayi, which cause river blindness and lymphatic filariasis, respectively. Bone-marrow-derived CD11c(+) cells from C57BL/6 and TLR4(-/-) mice produced high levels of IL-6 and RANTES, and showed elevated surface CD40 expression, whereas CD11c(+) cells from myeloid differentiation factor 88(-/-) (MyD88(-/-)), TLR2(-/-) and TLR2/4(-/-) mice were not activated. Similarly, IFN gamma production by splenocytes from immunized TLR2(-/-) mice was significantly impaired compared with splenocytes from C57BL/6 and TLR4(-/-) mice. In contrast, there was no difference among these strains in Th2-associated responses including IL-5 production by splenocytes from immunized animals, serum IgE and IgG(1), or eosinophil infiltration into the corneal stroma. Neutrophil recruitment to the cornea and CXC chemokine production was inhibited in immunized TLR2(-/-) mice compared with C57BL/6 and TLR4(-/-) mice. Taken together, these findings demonstrate an essential role for TLR2 in filaria-induced dendritic cell activation, IFN-gamma production and neutrophil migration to the cornea, but does not affect filaria-induced Th2-associated responses. PMID- 17727570 TI - Lipopopeptidephosphoglycan from Entamoeba histolytica activates human macrophages and dendritic cells and reaches their late endosomes. AB - Lipopopeptidephosphoglycan (LPPG) is a complex macromolecule from the surface of Entamoeba histolytica trophozoites. We analysed the interaction between LPPG and human macrophages and dendritic cells (DCs) and found that LPPG is internalized by these cells and activates them. The internalization process involves intracellular traffic from the cell membrane to late endosomes, as shown by co localization of LPPG with late endosomes marked with FITC-dextran and LAMP-1. LPPG-activated DCs have increased expression of co-stimulatory molecules CD80, CD86 and CD40 and produce pro-inflammatory cytokines TNF-alpha, IL-8 and IL-12. Taken together, these results show that LPPG activates antigen-presenting cells and reaches intracellular compartments that are involved in antigen presentation. PMID- 17727571 TI - Differential regulation of IgG subclasses and IgE antimalarial antibody responses in complicated and uncomplicated Plasmodium falciparum malaria. AB - The aim of this study was to assess the immunoglobulin (Ig)-subclass distribution of antimalarial antibody responses in 110 and 169 Thai patients with complicated and uncomplicated Plasmodium falciparum malaria, respectively. Antimalarial plasma IgG subclasses and IgE antibody levels against a crude malaria blood stages, and antigen preparation were determined using enzyme-linked immunosorbent assay (ELISA). On admission, the levels of anti-P. falciparum IgG1, IgG2 and IgG3 were significantly lower in patients with complicated malaria than uncomplicated malaria (IgG1, P < 0.0001; IgG2, P < 0.0001; IgG3, P < 0.0001). The levels of antimalarial IgE were slightly lower, but not statistically significant (P = 0.389) in the complicated malaria. After adjusting all antibody levels and age, anti-P. falciparum IgG3 levels remained significantly associated with complicated malaria. None of the other antibody concentrations showed statistically significant associations with complicated malaria. The anti-P. falciparum IgG3 levels were related to the IgG1 as well as IgG2 levels. A correlation between anti-P. falciparum IgG2 and IgE was observed in the complicated malaria group, and this may indicate their roles in the severity of disease. Our data suggest that anti-P. falciparum IgG3 is associated with a reduced risk of complicated malaria and that antimalarial Ig-subclasses are differently regulated in patients with complicated and uncomplicated malaria. PMID- 17727572 TI - Antidiuretic therapy for bladder disorders. PMID- 17727573 TI - Basis and therapeutical rationale of the urinary concentrating mechanism. AB - The urine-concentrating mechanism performs one of the most essential functions in water and electrolyte metabolism and serves primarily to maintain extracellular osmolality within a very narrow range. The history of anti-diuresis dates back more than 100 years and includes the discovery of antidiuretic hormone (AVP), the renal AVP receptor, and most recently the water channel (aquaporin) proteins. Today, the mechanisms of antidiuresis are understood on a highly detailed molecular level including both short term and long-term regulation of AQP2 function. Furthermore, the background behind many acquired and inherited disturbances of water balance has now been revealed and has enabled a precise differential diagnosis. These include different forms of diabetes insipidus, nocturnal enuresis and nocturia in the elderly. Diabetes insipidus represents a dramatic but rare disturbance of water balance caused by deficient AVP secretion (neurogenic), reduced renal sensitivity to AVP (nephrogenic), an abnormally high fluid intake (primary polydipsia), or in rare cases by placental enzymatic degradation of AVP (gestational). Nocturnal enuresis and nocturia in the elderly represents much more common disturbances and share common pathogenic features including an abnormally high nocturnal urine production. This seems at least in part to be caused by abnormally low levels of plasma AVP during night. The increased understanding of such water balance disturbances have changed dramatically prior treatment practice by introducing antidiuresis as a treatment modality. The ongoing progress in our understanding of antidiuresis may provide the basis for the development of new antidiuretic compounds. PMID- 17727574 TI - Primary monosymptomatic nocturnal enuresis in children and adolescents. AB - Nocturnal enuresis (NE) is one of the most frequent paediatric pathologies. The prevalence of primary nocturnal enuresis (PNE) is around 9% in children between 5 and 10 years of age and about 40% of them have one or more episodes per week. Still for too long, PNE has not been recognised as a pathological condition, particularly by the medical community; as a consequence, there was no specific education at medical school, and a poor involvement by the practitioners. Enuretic children have a sense of social difference and isolation; some of them do express a low self-esteem. Also, self-esteem is improved by the management NE even if this management fails to cure the condition. Primary monosymptomatic nocturnal enuresis (PMNE) is an heterogeneous condition for which various causative factors have been identified such as: nocturnal polyuria, sleep disturbances, reduced bladder capacity or bladder dysfunction, upper airway obstruction. The positive diagnosis of PMNE is based on a complete questionnaire and a careful physical examination. A drinking and voiding chart is an essential non-invasive tool: first, to collect information about the initial drinking and voiding habits of the child, then to reassess the accuracy of the diagnosis. Only motivated patients should receive a specific treatment for their NE and the treatment should be proposed based on the type of PMNE. PMNE associated with nocturnal polyuria should be treated with desmopressin, which reduces nighttime urine production. For PMNE with a reduced bladder capacity alarms should be the first-line treatment. Oxybutinin, a drug with anticholinergic properties, is not theoretically indicated for the treatment of PMNE except for a very small subgroup of patients who have an overactive bladder only during sleep. In cases refractory to monotherapy, NE is probably the result of an association of different physiopathological factors (e.g. both a nocturnal polyuria together with a small bladder capacity) some of them are still unknown. In these patients, a combination of treatments may be more effective than monotherapy. Various combination therapies can be proposed to improve the cure rates. PMID- 17727575 TI - Nocturia in men. AB - Nocturia is a common source of sleep disturbance in men and can result from many different causes. A patient-generated frequency/volume chart, along with several simple mathematical formulas, is used to classify nocturia according to its principal aetiology. The categories are nocturnal polyuria (NP), reduced voided volumes, 24-h polyuria and a combination of the aforementioned factors. Identification of the precise type of nocturia can help direct treatment in the cause-specific manner. In particular, use of the antidiuretic desmopressin can be of benefit in those with NP and may also be useful as part of a combination treatment approach in nocturia of mixed aetiology. PMID- 17727576 TI - Nocturia in women. AB - Nocturia, the complaint of waking at night to void, is a bothersome condition known to affect Quality of Life. In addition sleep deprivation is also known to affect daytime functioning and productivity. Whilst recently recognised as a discrete clinical entity nocturia is also a symptom of those women complaining of Overactive Bladder (OAB) syndrome. The causes of nocturia are multifactorial although in clinical practice nocturia is generally associated with either increased nocturnal urine production, problems related to bladder storage or sleep pattern abnormalities. When evaluating women complaining of nocturia a urinary diary and clinical examination is integral to making the diagnosis prior to commencing treatment. Having excluded and treated any underlying cause behavioural modification, such as moderation of fluid intake or timing of taking anti-diuretic medication, should be considered first line therapy. Should this conservative approach fail then treatment with antimuscarinic agents or desmopressin, a nona-peptide analogue of anti-diuretic hormone (ADH) is often helpful. PMID- 17727577 TI - Novel uses for antidiuresis. AB - Overactive bladder (OAB) is a bothersome condition that affects millions of people worldwide. It consists of urgency, incontinence, frequency and nocturia. Treatment, in the form of lifestyle interventions, bladder training and pelvic floor muscle exercises, aim to alleviate symptoms. These treatment modalities have drawbacks, including being time consuming and require stamina on the part of the patient and treating physician. Drugs may be used if conservative measures fail or in combination with them. Antimuscarinics are the mainstay of OAB medication but may cause dry mouth, blurred vision or constipation. It is, therefore, crucial that new treatment modalities are sought to help with this potentially debilitating condition. Antidiuresis, using desmopressin, forms a potential candidate for a novel treatment. As the bladder fills with urine, symptoms of OAB are experienced by patients. It would be reasonable to hypothesise that if the rate of bladder filling is reduced then so would the symptoms of OAB. Desmopressin reduces the production of urine by the kidneys, therefore reducing the amount of urine in the bladder and, therefore, the symptoms of OAB. Desmopressin has been used previously in small single centre trials in neurogenic OAB patients with some success but recently two multi centre, multinational randomised placebo controlled trials using this concept have been completed in idiopathic OAB sufferers and reported in the literature. The results were quite promising although there were minor side effects. These trials suggest that this potential novel treatment modality for OAB sufferers might avoid the necessity for invasive treatments, such as botulinum toxin, neuromodulation or surgery, in some instances. These trials also open the way to combination therapy with current treatment modalities of OAB. PMID- 17727578 TI - Intervention studies in JCN. PMID- 17727580 TI - Intravenous fluid therapy: a randomized controlled trial to investigate the effectiveness of the IV(2) flow medical device. AB - OBJECTIVES: To investigate the hypothetical benefits of the IV(2) flow medical device. BACKGROUND: Intravenous fluid administration is a standard hospital procedure with assumed inadequacies. The IV-Event Study [Fraser N, Nel G, Snyman J & Wessels F (2004) IV-EVENT Study: Intravenous Infusion Therapy--Management and Adverse Events. Data on File: Varori International (Pty) Ltd., Centurion, South Africa] quantified these inadequacies; The 'Stargait' intervention trial investigated the effectiveness and possible cost-benefit of the IV(2) flow. The IV(2) flow is intended for routine use with gravitational intravenous infusion sets. The IV(2) flow should reduce the incidence rate of adverse events and maintain a set flow rate. METHOD: Nursing staff assisted by study assessors captured relevant data. Consented patients were enrolled for the period of their prescribed infusions. Intervention. The Stargait Trial compared the treatment group (standard gravitational sets with the IV(2) flow) with the control group (standard gravitational infusion sets without IV(2) flow). The difference in observed events and the cost benefit derived from this were measured. RESULTS: A total of 2387 drip hours were observed in 52 patients. The adverse event rates were: Control group (without IV(2) flow) 33.8%. The treatment group (IV(2) flow) 15.4%. This 55% reduction is statistically significant (p = 0.0069). Adverse event related monetary wastage (labour and consumables) is reduced by 76% for infusion bags in the intervention group (with IV(2) flow). There was a significant difference between the treatment group and control group as far as deviation in flow rate was concerned (p = 0.00818). The mean deviation of the IV(2) flow group was just more than 5 ml per hour. The standard line group had a mean deviation of more than 30 ml per hour. CONCLUSION: Gravitational intravenous therapy compromises quality of patient care. The Stargait Trial has proven the care-effectiveness and cost-effectiveness of the IV(2) flow. RELEVANCE TO CLINICAL PRACTICE: The IV(2) flow improves quality of patient care and reduces associated wastage. PMID- 17727581 TI - General surgical patients' perspectives of the adequacy and appropriateness of discharge planning to facilitate health decision-making at home. AB - AIM: To investigate general surgical patients' perspectives of the adequacy and appropriateness of their discharge planning. OBJECTIVES: To identify any aspects of discharge planning that could be strengthened to assist people in managing their posthospital care and maintaining continuity of care. BACKGROUND: Appropriate discharge planning is a priority in today's healthcare environment in which patients are discharged 'quicker and sicker', sometimes without home support. Adequate and appropriate discharge planning helps promote health literacy, which has benefits for both patients and their caregivers in helping them manage postsurgical recovery at home. DESIGN: A qualitative, interpretive study was designed in which patients were interviewed at least one week after they returned home from hospital. METHODS: Purposeful sampling was used to interview 13 general surgical patients from one of three hospitals (two public and one private) in New South Wales and Queensland, Australia. Data were collected in unstructured interviews and analysed using thematic analysis. Reflective analysis by individual research team members generated preliminary themes, which were then analysed collectively by all members of the research team to achieve consensus on patients' perspectives. RESULTS: Themes included a 'one size-fits-all' approach to providing discharge information; inconsistent or variable advice from different health professionals; a lack of predischarge assessment of their home and/or work conditions and the need for follow-up assessment of patient and carer needs. CONCLUSIONS: The findings of this study illuminate the need for a more individualized approach to discharge planning, taking into account the patient's age, gender, surgical procedure and family and community support for immediate and longer-term nursing follow-up. RELEVANCE TO CLINICAL PRACTICE: Patients would be more adequately prepared for their recovery period at home, by encouraging client-centred, interdisciplinary communication between health practitioners; adopting a flexible, approach to discharge planning which is tailored to individual needs of postsurgical patients, particularly in relation to advice and information related to recovery; and encouraging and supporting adequate health literacy for self-management. PMID- 17727582 TI - Newly qualified Irish nurses' interpretation of their preparation and experiences of registration. AB - AIMS AND OBJECTIVES: The aim of this paper is to report on the insights of newly qualified Irish nurses into their preparation for registration as general nurses and to develop insights into the postregistration experience. BACKGROUND: Nurse education in Ireland has undergone much reform over the past decade. These changes include the introduction of supernumerary status for nursing students and the formation of links with institutes of higher education. No Irish literature was found on this subject. METHOD: Individual semi-structured, in-depth interviews were held with 12 newly registered nurses, from two cohorts, within 10 months of qualification. A grounded theory approach was adopted and content analysis employed to analyse the data. RESULTS: Two categories, entitled Learning the Ropes and The Metamorphosis emerged from the analysis of data. Within each of these categories there were two subcategories. All respondents reported that since qualification, they had become increasingly conscious of their isolation and unmet needs as nursing students. Postregistration, they enjoyed their increased status and widespread recognition by others. CONCLUSIONS: This study details how improvements can be made at clinical level to assist the preparation of nursing students for registration. The positive aspects of registration are revealed through descriptions of comparisons of pre- and postregistration experiences, while the shortcomings of the journey to registration are described. RELEVANCE TO CLINICAL PRACTICE: Pre-registration nurses have unmet clinical needs which, if fulfilled, would benefit them post-registration. Good ward morale is elementary for student learning and enhances the post-registration experience. Registered nurses are highly conscious of their altered status. These findings are pertinent to clinicians and educationalists as they prepare nursing students for practice. PMID- 17727583 TI - Being family: the family experience when an adult member is hospitalized with a critical illness. AB - AIMS AND OBJECTIVES: The purpose of this qualitative study was to understand and interpret the 'family experience' with an adult member hospitalized with a critical illness. BACKGROUND: Nursing practice in critical care settings has traditionally focused on individual patient needs with only tangential recognition of family needs. Investigation to describe the family experience to illuminate family nursing practice has been lacking. The majority of studies thus far related to critical illness and family are quantitative and reveal constraints to family care and problematic nurse-family interactions. The logical next step is a new kind of family research to enhance nursing of the family as a whole. DESIGN: Family systems theory and existential phenomenology provided the frameworks guiding the study. METHODS: Semi-structured 'family as a group' interviews were performed with 11 families. Data were analysed using Van Manen's hermeneutic method. Rigor was addressed with trustworthiness criteria. RESULTS: The family experience was analysed within Van Manen's framework of lived space, lived relation, lived body and lived time. A constitutive pattern of being family was revealed. CONCLUSIONS: Being family bonds families and makes them exceedingly strong during the critical illness experience. Being a family unit is what gives most families the ability to endure the emotional upheaval and suffering that come with the critical illness experience. RELEVANCE TO CLINICAL PRACTICE: Nurses have profound power to help families bear this experience. Family caring is enhanced with the presence of nurses who recognize the importance of 'Being Family' for the family, acknowledge the significance of the nurse-family relationship and act on a commitment to be with and for the family. PMID- 17727584 TI - Promoting evidence-based care through a clinical research fellowship programme. AB - AIM: This paper reports on the development and evaluation of a multidisciplinary critical appraisal and research utilization-training programme at one organization with the aim of demonstrating a potential approach to the challenge of ensuring practice is evidence based. BACKGROUND: Considerable time and attention is devoted to developing and evaluating new clinical innovations. Nevertheless, it is estimated that a quarter of patients continue to receive treatments that are unnecessary or potentially harmful. DESIGN: A cross-sectional qualitative evaluation survey of nurses and allied health staff participating in the training programme. METHODS: After running the programme twice at this organization we sought to evaluate the impact of the programme. Participants were asked to write answers to open-ended questions to examine personal and professional outcomes of participation. RESULTS: All respondents found the programme to be worthwhile and beneficial to their everyday practice. Importantly, participants reported feeling more confident when discussing clinical issues within the multidisciplinary team. The majority have presented their work via oral presentations or in publications and many have gone on to enroll in higher degrees. CONCLUSIONS: A critical appraisal and research utilization programme, as described here, has benefits for clinicians in terms of building confidence, knowledge and skill acquisition and also for the organization in terms of provision of evidence-based care and quality and safety. It successfully addresses commonly reported barriers to research utilization. RELEVANCE TO CLINICAL PRACTICE: A programme such as the Clinical Research Fellowship increases clinicians' ability and confidence to generate research questions that are meaningful to practice and then investigate the issue in a rigorous and timely manner. PMID- 17727585 TI - Job satisfaction and importance for intensive care unit research coordinators: results from binational survey. AB - OBJECTIVE: To measure Intensive Care Unit Research coordinator job satisfaction and importance and to identify priorities for role development. BACKGROUND: Research coordinator numbers are growing internationally in response to increasing clinical research activity. In Australia, 1% of registered nurses work principally in research, many as Research coordinators. Internationally, the Association of Clinical Research Professionals currently has 6536 certified Research coordinators in 13 countries, with likely additional large numbers practicing without the voluntary certification. Research coordinators are almost always nurses, but little is know about this emerging specialty. Design. Cross sectional study using anonymous self-report questionnaire. METHODS: After ethics approval, the McCloskey-Mueller Satisfaction Scale and McCloskey-Mueller Importance Scale were administered via the Internet. The sample was 49 (response rate 71%) Research coordinators from the Australia and New Zealand Intensive Care Unit Research coordinators' Interest Group. RESULTS: Research coordinators were satisfied with structural aspects of the position working business hours; flexibility of working hours; high levels of responsibility and control over their work. Dissatisfaction was expressed regarding: remuneration and recognition; compensation for weekend work; salary package; career advancement opportunities; and childcare facilities. CONCLUSIONS: High priorities for role development are those rated highly important but with much lower satisfaction. These are: compensation for weekend call-out work; salary and remuneration package; recognition by management and clinicians; career advancement opportunities; departmental research processes; encouragement and feedback; and number of working hours. RELEVANCE TO CLINICAL PRACTICE: Increasing numbers of nurses have been attracted to this clinically based research position. These data contribute to the understanding and development of the role. PMID- 17727586 TI - Factual memories of ICU: recall at two years post-discharge and comparison with delirium status during ICU admission--a multicentre cohort study. AB - AIMS AND OBJECTIVE: To examine the relationship between observed delirium in ICU and patients' recall of factual events up to two years after discharge. BACKGROUND: People, the environment, and procedures are frequently cited memories of actual events encountered in ICU. These are often perceived as stressors to the patients and the presence of several such stressors has been associated with the development of reduced health-related quality of life or post-traumatic stress syndrome. DESIGN: Prospective cohort study using interview technique. METHOD: The cohort was assembled from 152 patients who participated in a previously conducted multi-centre study of delirium incidence in Australian ICUs. The interviews involved a mixture of closed- and open-ended questions. Qualitative responses regarding factual memories were analysed using thematic analysis. A five-point Likert scale with answers from 'always' to 'never' was used to ask about current experiences of dream, anxiety, sleep problems, fears, irritability and/or mood swings. Scoring ranged from 6 to 30 with a mid-point value of 18 indicating a threshold value for the diagnosis of post-traumatic stress syndrome. A P-value of <0.05 was considered significant for all analyses. RESULTS: Forty-one (40%) out of 103 potential participants consented to take part in the follow-up interview; 18 patients (44%) had been delirious and 23 patients (56%) non-delirious during the ICU admission. The non-participants (n = 62) formed a control group to ensure a representative sample; 83% (n = 34) reported factual memories either with or without recall of dreaming. Factual memories were significantly less common (66% cf. 96%) in delirious patients (OR 0.09, 95%CI 0.01-0.85, p = 0.035). Five topics emerged from the thematic analysis: 'procedures', 'staff', 'comfort', 'visitors', and 'events'. Based on the current experiences, five patients (12%, four non-delirious and one delirious) scored > or =18 indicative of symptoms of post-traumatic stress syndrome; this did not reach statistical significance. Memory of transfer out of ICU was less frequent among the delirious patients (56%, n = 10) than among the non-delirious patients (87%, n = 20) (p = 0.036). CONCLUSION: Most patients have factual memories of their ICU stay. However, delirious patients had significantly less factual recall than non-delirious patients. Adverse psychological sequelae expressed as post traumatic stress syndrome was uncommon in our study. Every attempt must be made to ensure that the ICU environment is as hospitable as possible to decrease the stress of critical illness. Post-ICU follow-up should include filling in the 'missing gaps', particularly for delirious patients. Ongoing explanations and a caring environment may assist the patient in making a complete recovery both physically and mentally. RELEVANCE TO CLINICAL PRACTICE: This study highlights the need for continued patient information, re-assurance and optimized comfort. While health care professionals cannot remove the stressors of the ICU treatments, we must minimize the impact of the stay. It must be remembered that most patients are aware of their surroundings while they are in the ICU and it should, therefore, be part of ICU education to include issues regarding all aspects of patient care in this particularly vulnerable subset of patients to optimize their feelings of security, comfort and self-respect. PMID- 17727587 TI - Effect of an evidence-based education programme on ED discharge advice for febrile children. AB - AIMS: This study aimed to examine the effect of an educational intervention on discharge advice given to parents leaving the emergency department with a febrile child. BACKGROUND: Childhood fever is a common reason to seek emergency care. Many children are discharged from the emergency department with fever as a significant component of their illness; therefore, it is vital that emergency department medical and nursing staff provide accurate and reliable information about childhood fever management. DESIGN: A pre/post-test design was used. The outcome measure was parental advice regarding paediatric fever management and the intervention for the study was an educational intervention for emergency department nursing staff that consisted of two tutorials. Data were collected using structured telephone interviews. RESULTS: Data were collected from 22 families during the pretest period and 18 families during the post-test period. The number of parents leaving the emergency department with no advice decreased by 48% (p = 0.002). Reports of written advice increased by 69.7% (p < 0.001) and there was a 38.4% increase in reports of verbal advice (p = 0.014). Parents leaving the emergency department with both written and verbal advice increased from 0 to 55.6% (p < 0.001). Reports of advice by nursing staff increased by 52% (p < 0.001) and there were significant increases in specific instructions related to oral fluid administration (22.7 vs. 77.8, p = 0.001) and use of antipyretic medications (27.2 vs. 77.8, p = 0.001). CONCLUSION: Evidence-based education of emergency nurses improved both the amount and quality of discharge advice for parents of febrile children. RELEVANCE TO CLINICAL PRACTICE: Parents and health care professionals alike need to better understand the physiological benefits of fever and the potential harmful effects of aggressive and often unwarranted treatment of fever. PMID- 17727588 TI - The effect of aromatherapy massage with music on the stress and anxiety levels of emergency nurses: comparison between summer and winter. AB - AIMS AND OBJECTIVES: This research aimed to evaluate the use of aromatherapy massage and music as an intervention to cope with the occupational stress and anxiety that emergency department staff experience. The study also aimed to compare any differences in results between a summer and winter 12-week massage plan. BACKGROUND: Emergency nurses are subjected to significant stressors during their work and it is known that workloads and patient demands influence the role stress has on nurses. The perception that winter months are busier for emergency departments has long been held and there is some evidence that people with cardiac and respiratory dysfunction do present more frequently in the winter months. Massage has been found to decrease staff anxiety. DESIGN: The study used a one-group pre-test, post-test quasi-experimental design with random assignment. METHOD: Staff occupational stress was assessed pre- and post- 12 weeks of aromatherapy massage with music and anxiety was measured pre and post each massage session. Sick leave was also measured. Comparisons of summer and winter data were undertaken. RESULTS: A total of 365 massages were given over two 12 week periods, one during summer and the other during winter. Analysis identified that aromatherapy massage with music significantly reduced anxiety for both seasonal periods. Premassage anxiety was significantly higher in winter than summer. No differences in sick leave and workload were found. There was no difference in the occupational stress levels of nurses following the two 12-week periods of massage. CONCLUSION: Emergency nurses were significantly more anxious in winter than summer but this cannot be attributed to increased sick leave or workloads. Aromatherapy massage with music significantly reduced emergency nurses' anxiety. RELEVANCE TO CLINICAL PRACTICE: High levels of anxiety and stress can be detrimental to the physical and emotional health of emergency nurses and the provision of a support mechanism such as on-site massage as an effective strategy should be considered. PMID- 17727589 TI - Daily life after moving into a care home--experiences from older people, relatives and contact persons. AB - AIMS AND OBJECTIVES: To describe older people's experiences of daily life at the care home after admittance with respect to their perceptions of participation in the decision to move. Furthermore, the aim was to study the experiences of their relatives and contact persons with respect to the daily life of the same residents. BACKGROUND: When older persons move into a care home, the whole family often play an important part. Thus, it is interesting to study how newly admitted older people, their relatives and staff members experience daily life in a modern care home. METHODS: Qualitative design. The participants comprised a purposive sample of 13 residents, recently admitted to a care home, 69-90 years old, both single living and married, both moving from their own homes and from different institutions. Interviews were carried out with the older people (n = 13), their relatives (n = 10) and contact persons (n = 11). RESULTS: The majority of the residents reported satisfaction with care home living. The relatives were also satisfied, secure and appreciated the privacy and homely atmosphere of the flat. The disadvantage of one-room flats was that the residents might have felt lonely. The relatives felt that the residents were bored, but few residents desired more activities, even if some of them longed for people to socialize with. For many older people, perhaps talking is the most important 'activity' at care homes. Concerning self-determination, some residents did not find it satisfactory. RELEVANCE TO CLINICAL PRACTICE: Staff members must pay attention to residents' need to talk with people. For many older people, talking is perhaps the most important 'activity' at care homes. Nurses must safeguard residents' self determination. When residents are in control of their lives, they may become satisfied with time. PMID- 17727590 TI - Depressive symptoms among older residents at nursing homes in Taiwan. AB - AIMS AND OBJECTIVES: To examine the depressive symptoms of older residents at nursing homes and the relationship between their depressive symptoms and certain selected variables. BACKGROUND: Depression has become a major healthcare concern among the older people, but nursing home-based studies on risk factors of depression have still hardly been well performed in Taiwan. DESIGN: A cross sectional design was developed and implemented. METHODS: A research sample of 138 older residents was recruited from eight nursing homes located in southern Taiwan. During face-to-face interviews, the Center for Epidemiological Studies Depression Scale, Social Support Scale, Chronic Condition Checklist and Socio demographic Inventory were used for data collection. RESULTS: The results showed that 81.8% of those residents were identified as being depressed. It was further discovered that the length of residency, number of chronic conditions, perceived health status and the amount of social support from their family and relatives could explain 38.8% of the total variances in depressive symptoms. CONCLUSIONS: Our study suggests that, in Taiwan, older people who live in nursing homes suffer from more depressive symptoms than those in community dwellings. To maintain and improve the health status for the elderly as much as possible, it is suggested that healthcare providers at nursing homes should develop an effective health promotion program for these older peoples. RELEVANCE TO CLINICAL PRACTICE: There exists a high rate of depressive symptoms among older residents at nursing homes. It is imperative that a proper identification and its correspondent treatment for this health problem on the older residents are required. In late life, to maintain a higher level of quality of life, it is important to suggest that the health providers should regularly screen older people to increase the likelihood of diagnosis and improved treatment of late-life depressive symptoms. PMID- 17727591 TI - An exploration of the smoking-related health beliefs of older people with chronic obstructive pulmonary disease. AB - AIM: To explore the smoking-related health beliefs of older people with chronic obstructive pulmonary disease (COPD). BACKGROUND: Globally, smoking is a major cause of COPD and symptoms present typically mid to later life. Substantial numbers of people with COPD continue to smoke even though smoking cessation is known to slow the rate of disease progression and prevent further deterioration in lung function. There is evidence to suggest that, although older long-term smokers can successfully quit smoking with the help of specialist structured programmes, those with COPD find it more difficult to achieve sustained cessation. An understanding of the health beliefs of people with COPD will assist professionals to provide the most appropriate support with cessation attempts. DESIGN: A secondary analysis of qualitative interview data. METHODS: Twenty-two current and former smokers with COPD who used the outreach service of an inner city hospital in Scotland were interviewed in their own homes using semi structured interviews which were transcribed verbatim. The main concepts of the Health Belief Model were used as an analysis framework. FINDINGS: Interviews were carried out with 15 women and seven men with a median age of 68 years. Almost 90% lived in areas of the highest socio-economic deprivation according to DEPCAT scores. Almost two-thirds of the individuals in this study continued to smoke even though they largely perceived smoking as a threat to health. Individuals who continued to smoke cited various barriers to quitting smoking and all had, at some time, attempted smoking cessation. Over half were still attempting to quit. Cues to action came from external sources rather than increasing disease severity. CONCLUSIONS: Cessation is challenging and knowledge of a person's health beliefs is a prerequisite to supporting behaviour change. RELEVANCE TO CLINICAL PRACTICE: Findings emphasize the need for frontline health professionals to reflect on their current practice with a view to providing sustained encouragement and support towards smoking cessation and relapse prevention for people with COPD. PMID- 17727592 TI - Care for emergency department patients who have experienced domestic violence: a review of the evidence base. AB - AIMS: A literature review was conducted to identify and evaluate the research base underpinning care for emergency department patients who have experienced domestic violence. BACKGROUND: The extent of domestic violence in the general population has placed it high on health and social policy agendas. The Department of Health has recognized the role of health care professionals to identify and provide interventions for patients who have experienced domestic violence. METHOD: Systematic review. RESULTS: At least 6% of emergency department patients have experienced domestic violence in the previous 12 months although actual prevalence rates are probably higher. Simple direct questioning in a supportive environment is effective in facilitating disclosure and hence detecting cases of abuse. Although routine screening is most effective, index of suspicion screening is the current mode of practice in the UK. Index of suspicion screening is likely to contribute to under-detection and result in inequitable health care. Patients with supportive networks have reduced adverse mental health outcomes. Women will have negative perceptions of emergency care if their abuse is minimalized or not identified. Women want their needs and the needs of their children to be explored and addressed. Access to community resources is increased if patients receive education and information. CONCLUSION: Domestic violence is an indisputable health issue for many emergency department patients. Practitioners face challenges from ambiguity in practice guidelines and the paucity of research to support interventions. Recommendations for practice based on the current evidence base are presented. RELEVANCE TO CLINICAL PRACTICE: The nursing care for patients in emergency and acute health care settings who have experienced domestic violence should focus on three domains of: (1) Providing physical, psychological and emotional support; (2) Enhancing safety of the patient and their family; (3) Promoting self-efficacy. PMID- 17727593 TI - Relatives' struggle for an improved and more just care for older people in community care. AB - AIMS AND OBJECTIVES: The aim of the present study was to describe the relatives' experience concerning older family members living in special housing facilities. BACKGROUND: During the 21st century, the relatives of older people and their efforts related to the care and nursing of older people have been observed. The interest in these relatives is because of factors such as demographic changes, where the number of older people has increased and the increasing gap between the resources that are available for geriatric care and the care needed for older people. DESIGN: The present study has a descriptive design and is part of a project including 24 specific residences, called special housing facilities. METHOD: The study focused on the narratives supplied by the relatives that were analysed using qualitative latent content analysis, an interpretative process where the researcher considers the content of the text. RESULTS: The relatives' experience of having an older person in a special housing facility that emerged from the study, was expressed in one main theme: The relatives' struggle for an improved and just care for older people and four sub-themes: (i)'To trust in caregivers'; (ii) 'To be confirmed'; (iii) 'To trust in care'; (iv) 'To receive the kind of care that one considers one has the right to receive'. CONCLUSIONS: The study shows that the relatives need more support and more opportunities, so that they can participate in the care. The study shows the relatives engagement in working for a just society's obligation towards the protection of older peoples rights and the staff's working conditions. RELEVANCE TO CLINICAL PRACTICE: It is important that caregivers and management working with older people realize that they, together with them and their relatives, are a part of society and that all individuals are influenced by the discourse of that society. PMID- 17727594 TI - The revolving door syndrome: the Chinese COPD patients' perspectives. PMID- 17727595 TI - Commentary on Liu J, Mok E and Wong T (2006) Caring in nursing: investigating the meaning of caring from the perspective of cancer patients in Beijing, China. Journal of Clinical Nursing 15, 188-196. PMID- 17727596 TI - Commentary on Roxburgh M (2006) An exploration of factors which constrain nurses from research participation. Journal of Clinical Nursing, 15, 535-545. PMID- 17727599 TI - Commentary on Rydstrom I, Dalheim-Englund A-C, Holritz-Rasmussen B, Moller C & Sandman P-O (2005) Asthma--quality of life for Swedish children. Journal of Clinical Nursing 14, 739-749. PMID- 17727598 TI - Commentary on Roxburgh M (2006) An exploration of factors which constrain nurses from research participation. Journal of Clinical Nursing 15, 535-545. PMID- 17727601 TI - Commentary on Lambert V and Glacken M (2005) Clinical education facilitators: a literature review. Journal of Clinical Nursing 14, 664-673. PMID- 17727602 TI - Commentary on Hung C-H (2006) Revalidation of the postpartum stress scale. Journal of Clinical Nursing 15, 718-725. PMID- 17727604 TI - Commentary on Dobrzanska L & Newell R (2006) Readmissions: a primary care examination of reasons for readmission of older people and possible readmission risk factors. Journal of Clinical Nursing 15, 599-606. PMID- 17727607 TI - Commentary on Schroder A, Ahlstrom G & Larsson BW (2006) Patients' perceptions of the concept of the quality of care in the psychiatric setting: a phenomenographic study. Journal of Clinical Nursing 15, 93-102. PMID- 17727606 TI - Commentary on Twycross A and Powls L (2006) How do children's nurses make clinical decisions? Two preliminary studies. Journal of Clinical Nursing 15, 1324 1335. PMID- 17727609 TI - Commentary on Chan MF, Yee ASW, Leung ELY & Day MC (2006) The effectiveness of a diabetes nurse clinic in treating older patients with type 2 diabetes for their glycaemic control. Journal of Clinical Nursing 15, 770-781. PMID- 17727612 TI - Dihydrodipicolinate reductase-like protein, CRR1, is essential for chloroplast NAD(P)H dehydrogenase in Arabidopsis. AB - Chloroplast NAD(P)H dehydrogenase (NDH) is a homolog of the bacterial NADH dehydrogenase NDH-1 and is involved in cyclic electron transport around photosystem I. In higher plants, 14 subunits of the NDH complex have been identified. The subunit that contains the electron donor-binding site or an electron donor to NDH has not been determined. Arabidopsis crr1 (chlororespiratory reduction 1) mutants were isolated by chlorophyll fluorescence imaging on the basis of their lack of NDH activity. CRR1 is homologous to dihydrodipicolinate reductase (DHPR), which functions in a lysine biosynthesis pathway. However, the dihydrodipicolinate-binding motif was not conserved in CRR1, and the crr1 defect was specific to accumulation of the NDH complex, implying that CRR1 is not involved in lysine biosynthesis in Arabidopsis. Similarly to other nuclear-encoded genes for NDH subunits, CRR1 was expressed only in photosynthetic tissue. CRR1 contained a NAD(P)H-binding motif and was a candidate electron donor-binding subunit of the NDH complex. However, CRR1 was detected in the stroma but not in the thylakoid membranes, where the NDH complex is localized. Furthermore, CRR1 was stable in crr2-2 lacking the NDH complex. These results suggest that CRR1 is involved in biogenesis or stabilization of the NDH complex, possibly via the reduction of an unknown substrate. PMID- 17727613 TI - Transcription factor AtMYB103 is required for anther development by regulating tapetum development, callose dissolution and exine formation in Arabidopsis. AB - Downregulation of the transcription factor AtMYB103 using transgenic technology results in early tapetal degeneration and pollen aberration during anther development in Arabidopsis thaliana. This paper describes the functional analysis of the AtMYB103 gene in three knock-out mutants. Two male sterile mutants, ms188 1 and ms188-2, were generated by ethyl-methane sulfonate (EMS) mutagenesis. A map based cloning approach was used, and ms188 was mapped to a 95.8-kb region on chromosome 5 containing an AtMYB103 transcription factor. Sequence analysis revealed that ms188-1 had a pre-mature stop codon in the AtMYB103 coding region, whereas ms188-2 had a CCT-->CTT base-pair change in the first exon of AtMYB103, which resulted in the replacement of a proline by a leucine residue in the R2R3 domain. The third mutant, an AtMYB103 transposon-tagging line, also showed a male sterile phenotype. Allelism tests indicated that MS188 and AtMYB103 belong to the same locus. Cytological observation revealed defective tapetum development and altered callose dissolution in ms188 plants. Additionally, most of the microspores in mature anthers were degraded and surviving microspores lacked exine. AtMYB103 encoded an R2R3 MYB protein that is predominantly located in the nucleus. Real-time RT-PCR analysis indicated that the callase-related gene A6 was regulated by AtMYB103. Expression of the exine formation gene MS2 was not detected in mutant anthers. These results implicate that AtMYB103 plays an important role in tapetum development, callose dissolution and exine formation in A. thaliana anthers. PMID- 17727614 TI - Free-flow electrophoresis for purification of plant mitochondria by surface charge. AB - Sample purity is the key for a successful in-depth analysis of any given subcellular proteome. The suitability of free-flow electrophoresis to assist conventional, centrifugation-based techniques in the preparation of plant mitochondria from green and non-green tissue was assessed by various means, including functional assays, immunoblots, electron microscopy and differential gel electrophoresis. Results indicated a significant increase in purity of the mitochondrial samples, highlighted specific contaminants previously reported as mitochondrial proteins, and also pointed to new means for separating plastids and peroxisomes from mitochondria in plant organellar extracts by exploiting differences in surface charge. This approach has the potential to allow a deeper and more comprehensive investigation of the Arabidopsis organellar proteomes, by providing a second dimension of separation based on surface charge in addition to conventional centrifugation purification protocols relying on size and density. PMID- 17727615 TI - Characterization of Arabidopsis ABCG11/WBC11, an ATP binding cassette (ABC) transporter that is required for cuticular lipid secretion. AB - ABCG11/WBC11, an ATP binding cassette (ABC) transporter from Arabidopsis thaliana, is a key component of the export pathway for cuticular lipids. Arabidopsis wbc11 T-DNA insertional knock-out mutants exhibited lipidic inclusions inside epidermal cells similar to the previously characterized wax transporter mutant cer5, with a similar strong reduction in the alkanes of surface waxes. Moreover, the wbc11 knock-out mutants also showed defects not present in cer5, including post-genital organ fusions, stunted growth and a reduction in cutin load on the plant surface. A mutant line previously isolated in a forward genetics screen, called permeable leaves 1 (pel1), was identified as an allele of ABCG11/WBC11. The double knock-out wbc11 cer5 exhibited the same morphological and biochemical phenotypes as the wbc11 knock-out. A YFP-WBC11 fusion protein rescued a T-DNA knock-out mutant and was localized to the plasma membrane. These results show that WBC11 functions in secretion of surface waxes, possibly by interacting with CER5. However, unlike ABCG12/CER5, ABCG11/WBC11 is important to the normal process of cutin formation. PMID- 17727616 TI - The rice nuclear gene, VIRESCENT 2, is essential for chloroplast development and encodes a novel type of guanylate kinase targeted to plastids and mitochondria. AB - Guanylate kinase (GK) is a critical enzyme in guanine nucleotide metabolism pathways, catalyzing the phosphorylation of (d)GMP to (d)GDP. Here we show that a novel gene, VIRESCENT 2 (V2), encodes a new type of GK (designated pt/mtGK) that is localized in plastids and mitochondria. We initially identified the V2 gene by positional cloning of the rice v2 mutant. The v2 mutant is temperature-sensitive and develops chlorotic leaves at restrictive temperatures. The v2 mutation causes inhibition of chloroplast differentiation; in particular, it disrupts the chloroplast translation machinery during early leaf development [Sugimoto et al. (2004)Plant Cell Physiol. 45, 985]. In the bacterial and animal species studied to date, GK is localized in the cytoplasm and participates in maintenance of the guanine nucleotide pools required for many fundamental cellular processes. Phenotypic analysis of rice seedlings with RNAi knockdown of cytosolic GK (designated cGK) showed that cGK is indispensable for the growth and development of plants, but not for chloroplast development. Thus, rice has two types of GK, as does Arabidopsis, suggesting that higher plants have two types of GK. Our results suggest that, of the two types of GK, only pt/mtGK is essential for chloroplast differentiation. PMID- 17727617 TI - Molecular phenotyping of lignin-modified tobacco reveals associated changes in cell-wall metabolism, primary metabolism, stress metabolism and photorespiration. AB - Lignin is an important component of secondarily thickened cell walls. Cinnamoyl CoA reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD) are two key enzymes that catalyse the penultimate and last steps in the biosynthesis of the monolignols. Downregulation of CCR in tobacco (Nicotiana tabacum) has been shown to reduce lignin content, whereas lignin in tobacco downregulated for CAD incorporates more aldehydes. We show that altering the expression of either or both genes in tobacco has far-reaching consequences on the transcriptome and metabolome. cDNA-amplified fragment length polymorphism-based transcript profiling, combined with HPLC and GC-MS-based metabolite profiling, revealed differential transcripts and metabolites within monolignol biosynthesis, as well as a substantial network of interactions between monolignol and other metabolic pathways. In general, in all transgenic lines, the phenylpropanoid biosynthetic pathway was downregulated, whereas starch mobilization was upregulated. CCR downregulated lines were characterized by changes at the level of detoxification and carbohydrate metabolism, whereas the molecular phenotype of CAD-downregulated tobacco was enriched in transcript of light- and cell-wall-related genes. In addition, the transcript and metabolite data suggested photo-oxidative stress and increased photorespiration, mainly in the CCR-downregulated lines. These predicted effects on the photosynthetic apparatus were subsequently confirmed physiologically by fluorescence and gas-exchange measurements. Our data provide a molecular picture of a plant's response to altered monolignol biosynthesis. PMID- 17727618 TI - Feasibility and cost-benefit of implementing pooled screening for HCVAg in small blood bank settings. AB - To examine the accuracy, feasibility and benefits of screening for hepatitis C virus core antigen (HCVAg) using enzyme-linked immunosorbent assay (ELISA) test in pools. Many countries cannot afford to test blood donations for hepatitis C using molecular methods. Screening individual units using the ELISA HCVAg test is an acceptable, yet still expensive, alternative, especially for small blood bank settings. This study evaluated the option of screening for HCVAg in pools. The sensitivity (Se) and specificity (Sp) of HCVAg in pools of three and six antibody negative samples were estimated and compared with polymerase chain reaction (PCR). The feasibility and cost-benefit of the assay was assessed on 960 routine samples collected at a hospital blood bank in Gaza. Based on results for 50 PCR positive pools and 50 and 110 PCR-negative pools of three and six, the Se of testing in pools of three and six samples is 80-82% [95% confidence interval (CI): 66.3-91.4] and Sp >or=98% (95% CI: 89.4-100.0) compared with PCR. The incidence of antigen in donors in Gaza was 0.1% (95% CI: 0-0.56). Cost analyses suggested significant benefits from implementing screening blood donations for HCVAg when the incidence rate is >4.2/10,000, leading to reduction in the expenditures needed to treat patients infected with HCV. The risk of transfusion transmitted hepatitis C in resource-deprived developing countries can be efficiently reduced by additional screening of antibody-negative blood donations for HCVAg in pools of six. PMID- 17727619 TI - An intrarenal abscess as presenting symptom of an infection with Nocardia farcinica in a patient after renal transplantation. AB - A 52-year-old man presented 8 months after transplantation with an intrarenal mass, which proved to be caused by an infection with Nocardia farcinica. Because of the potential fatal course of nocardiosis, transplantectomy was performed and long-term antibiotic treatment was instituted. Three-and-a-half years later, this patient underwent successful re-transplantation under co-trimoxazole prophylaxis. At present, more than 1 year after his second transplant has been performed, there are no signs of recurrence of Nocardia infection. To our knowledge, this is the first report of a patient with nocardiosis with an intrarenal abscess as presenting symptom. PMID- 17727620 TI - Childhood obesity: political developments in Europe and related perspectives for future action on prevention. AB - The dramatically increasing prevalence of obesity, especially among children, has become a major public health problem in Europe. In reaction to this alarming trend, a series of initiatives and actions has been launched in recent years. As the potential impact of these activities is widely unknown so far, we underline the need for adequate evaluation of these measures. The aim of this paper is to report the latest developments in the fight against obesity at different political levels across Europe, with special attention to the major results of the recent World Health Organization European Ministerial Conference on Counteracting Obesity. In accordance with the main principles of the European Charter on Counteracting Obesity adopted at the meeting, immediate action should be taken now by implementing the few available schemes with proven effectiveness. Finally, given the lack of appropriate evaluation, we consider it particularly important to establish national research centres to collect country-specific data that are to be evaluated together by a central European administration department. Based on the results of such a comprehensive data pool, concrete strategies could be developed for future policy building. PMID- 17727621 TI - Across the great divide: genetic forensics reveals misidentification of endangered cutthroat trout populations. AB - Accurate assessment of species identity is fundamental for conservation biology. Using molecular markers from the mitochondrial and nuclear genomes, we discovered that many putatively native populations of greenback cutthroat trout (Oncorhynchus clarkii stomias) comprised another subspecies of cutthroat trout, Colorado River cutthroat trout (Oncorhynchus clarkii pleuriticus). The error can be explained by the introduction of Colorado River cutthroat trout throughout the native range of greenback cutthroat trout in the late 19th and early 20th centuries by fish stocking activities. Our results suggest greenback cutthroat trout within its native range is at a higher risk of extinction than ever before despite conservation activities spanning more than two decades. PMID- 17727622 TI - Biodiversity dynamics in isolated island communities: interaction between natural and human-mediated processes. AB - The flora and fauna of oceanic islands have inspired research since the early scientific explorations. Islands can be considered 'nature's test tubes'- simple systems with multiple replicates. Our research has used the simplicity of island systems to understand ecological community dynamics and to compare the properties of island communities with those in more complex mainland systems. Here, we present three topics: (i) current patterns of biodiversity on isolated islands of the Pacific; (ii) current patterns of disturbance and invasion on islands; and (iii) future trajectories inferred from these patterns. We examine features of islands (in particular, topography and isolation) that have allowed for given levels and distribution of endemicity. The extent to which island communities are impacted by, resist or accommodate disturbance and/or invasions by nonindigenous species appears to be dictated to a large extent by properties of the native communities and how these communities were originally assembled. Accordingly, patterns of disturbance and invasion are very different for high (montane) islands that are extremely isolated compared to those that are nearer to a source of natural migrants. As with all biotas, those on islands are dynamic entities. However, the unique aspect of islands is their isolation, and extreme isolation has largely been lost over the course of the last few centuries due to the development of transportation routes. We argue that such a modified dynamic will affect the future of the biota and the processes that gave rise to the biota. Specifically for isolated habitats, ecological processes will become increasingly more likely to generate biodiversity than evolutionary processes which have been relatively more important in the past. In the short term, island biotas and other similar biotas that occur in montane habitats may fare well as species are often abundant locally in the habitat to which they are indigenous, and may demonstrate considerable resistance and resilience to invasion. However, island biotas - and other biotas that show high local endemism - will likely not fare well in the face of prolonged disturbance. The biotas in these areas generally display a relatively low dispersal capacity; therefore, under conditions of long-term habitat modification, isolated biotas are likely to be swamped by non-natives, which - simply because of random processes and higher propagule pressure - will move more readily into available habitats. Thus, despite the importance of incorporating the evolutionary process into conservation efforts, we must also be careful to evaluate the likely form that the processes will take when the context (specifically, extent of isolation) has been highly modified. PMID- 17727623 TI - Genetic drift vs. natural selection in a long-term small isolated population: major histocompatibility complex class II variation in the Gulf of California endemic porpoise (Phocoena sinus). AB - Although many studies confirm long-term small isolated populations (e.g. island endemics) commonly sustain low neutral genetic variation as a result of genetic drift, it is less clear how selection on adaptive or detrimental genes interplay with random forces. We investigated sequence variation at two major histocompatibility complex (Mhc) class II loci on a porpoise endemic to the upper Gulf of California, Mexico (Phocoena sinus, or vaquita). Its unique declining population is estimated around 500 individuals. Single-strand conformation polymorphism analysis revealed one putative functional allele fixed at the locus DQB (n = 25). At the DRB locus, we found two presumed functional alleles (n = 29), differing by a single nonsynonymous nucleotide substitution that could increase the stability at the dimer interface of alphabeta-heterodimers on heterozygous individuals. Identical trans-specific DQB1 and DRB1 alleles were identified between P. sinus and its closest relative, the Burmeister's porpoise (Phocoena spinipinnis). Comparison with studies on four island endemic mammals suggests fixation of one allele, due to genetic drift, commonly occurs at the DQA or DQB loci (effectively neutral). Similarly, deleterious alleles of small effect are also effectively neutral and can become fixed; a high frequency of anatomical malformations on vaquita gave empirical support to this prediction. In contrast, retention of low but functional polymorphism at the DRB locus was consistent with higher selection intensity. These observations indicated natural selection could maintain (and likely also purge) some crucial alleles even in the face of strong and prolonged genetic drift and inbreeding, suggesting long-term small populations should display low inbreeding depression. Low levels of Mhc variation warn about a high susceptibility to novel pathogens and diseases in vaquita. PMID- 17727625 TI - Aldose reductase is implicated in high glucose-induced oxidative stress in mouse embryonic neural stem cells. AB - Oxidative stress caused by hyperglycemia is one of the key factors responsible for maternal diabetes-induced congenital malformations, including neural tube defects in embryos. However, mechanisms by which maternal diabetes induces oxidative stress during neurulation are not clear. The present study was aimed to investigate whether high glucose induces oxidative stress in neural stem cells (NSCs), which compose the neural tube during development. We also investigated the mechanism by which high glucose disturbs the growth and survival of NSCs in vitro. NSCs were exposed to physiological d-glucose concentration (PG, 5 mmol/L), PG with l-glucose (25 mmol/L), or high d-glucose concentration (HG, 30 or 45 mmol/l). HG induced reactive oxygen species production and mRNA expression of aldose reductase (AR), which catalyzes the glucose reduction through polyol pathway, in NSCs. Expression of glucose transporter 1 (Glut1) mRNA and protein which regulates glucose uptake in NSCs was increased at early stage (24 h) and became down-regulated at late stage (72 h) of exposure to HG. Inhibition of AR by fidarestat, an AR inhibitor, decreased the oxidative stress, restored the cell viability and proliferation, and reduced apoptotic cell death in NSCs exposed to HG. Moreover, inhibition of AR attenuated the down-regulation of Glut1 expression in NSCs exposed to HG for 72 h. These results suggest that the activation of polyol pathway plays a role in the induction of oxidative stress which alters Glut1 expression and cell cycle in NSCs exposed to HG, thereby resulting in abnormal patterning of the neural tube in embryos of diabetic pregnancy. PMID- 17727626 TI - Cell death in an ischemic infarct rim model. AB - Using an in vitro model that simulates the microenvironment in the ischemic infarct rim, we have examined the temporal profile and possible mechanisms of cell death in the neuropil (an astrocyte-rich area or ARA) of organotypic hippocampal slice cultures. Two-photon confocal microscopy, propidium iodide, and GFAP-GFP transgenic mice were used to confirm cell death in astrocytes. An 'ischemic solution' (IS) induced major cell death throughout the hippocampus over 24 h, with the earliest injury starting in ARA. Our studies using IS or ion replacements in IS revealed that cell death in ARA was modest when K(+) was increased or pH lowered. High K(+) is most effective in reducing cell death when HCO(3)(-) is normal or high. When Cl(-) or HCO(3)(-) was reduced, cell injury was worsened. 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) protected cells from IS-induced death in a dose-dependent manner (1-4000 micromol/L). We conclude that (i) various areas of the hippocampal formation respond differently to ionic replacements; (ii) K(+) interacts with other ions to protect cells in ARA; and (iii) DIDS has a substantial protective effect in ARA by blocking DIDS sensitive membrane exchangers or by interfering with intracellular signaling pathways. PMID- 17727627 TI - Magnetic resonance analysis of the effects of acute ammonia intoxication on rat brain. Role of NMDA receptors. AB - Acute ammonia intoxication leads to rapid death, which is prevented by blocking N methyl-d-aspartate (NMDA) receptors. The subsequent mechanisms leading to death remain unclear. Brain edema seems an important step. The aim of this work was to study the effects of acute ammonia intoxication on different cerebral parameters in vivo using magnetic resonance and to assess which effects are mediated by NMDA receptors activation. To assess edema induction, we injected rats with ammonium acetate and measured apparent diffusion coefficient (ADC) in 16 brain areas. We also analyzed the effects on T1, T2, and T2* maps and whether these effects are prevented by blocking NMDA receptors. The effects of acute ammonia intoxication are different in different brain areas. T1 relaxation time is reduced in eight areas. T2 relaxation time is reduced only in ventral thalamus and globus pallidus. ADC values increased in hippocampus, caudate-putamen, substantia nigra and cerebellar cortex, reflecting vasogenic edema. ADC decreased in hypothalamus, reflecting cytotoxic edema. Myo-inositol increased in cerebellum and substantia nigra, reflecting vasogenic edema. N-acetyl-aspartate decreased in cerebellum, reflecting neuronal damage. Changes in N-acetyl-aspartate, T1 and T2 are prevented by blocking NMDA receptors with MK-801 while changes in ADC or myo inositol (induction of edema) are not. PMID- 17727624 TI - Sulcal variability, stereological measurement and asymmetry of Broca's area on MR images. AB - Leftward volume asymmetry of the pars opercularis and pars triangularis may exist in the human brain, frequently referred to as Broca's area, given the functional asymmetries observed in this region with regard to language expression. However, post-mortem and magnetic resonance imaging (MRI) studies have failed to consistently identify such a volumetric asymmetry. In the present study, an analysis of the asymmetry of sulco-gyral anatomy and volume of this anterior speech region was performed in combination with an analysis of the morphology and volume asymmetry of the planum temporale, located within the posterior speech region, in 50 healthy subjects using MRI. Variations in sulcal anatomy were documented according to strict classification schemes and volume estimation of the grey matter within the brain structures was performed using the Cavalieri method of stereology. Results indicated great variation in the morphology of and connectivity between the inferior frontal, inferior precentral and diagonal sulci. There were significant inter-hemispheric differences in the presence of (1) the diagonal sulcus within the pars opercularis, and (2) horizontal termination of the posterior Sylvian fissure (relative to upward oblique termination), both with an increased leftward incidence. Double parallel inferior precentral sulci and absent anterior rami of the Sylvian fissure prevented stereological measurements in five subjects. Therefore volumes were obtained from 45 subjects. There was a significant leftward volume asymmetry of the pars opercularis (P = 0.02), which was significantly related to the asymmetrical presence of the diagonal sulcus (P < 0.01). Group-wise pars opercularis volume asymmetry did not exist when a diagonal sulcus was present in both or neither hemispheres. There was no significant volume asymmetry of the pars triangularis. There was a significant leftward volume asymmetry of the planum temporale (P < 0.001), which was significantly associated with the shape of the posterior Sylvian fissure as a unilateral right or left upward oblique termination was always associated with leftward or rightward volume asymmetry respectively (P < 0.01). There was no relationship between volume asymmetries of the anterior and posterior speech regions. Our findings illustrate the extent of morphological variability of the anterior speech region and demonstrate the difficulties encountered when determining volumetric asymmetries of the inferior frontal gyrus, particularly when sulci are discontinuous, absent or bifid. When the intrasulcal grey matter of this region is exhaustively sampled according to strict anatomical landmarks, the volume of the pars opercularis is leftward asymmetrical. This manuscript illustrates the importance of simultaneous consideration of brain morphology and morphometry in studies of cerebral asymmetry. PMID- 17727628 TI - Formyl peptide-receptor like-1 requires lipid raft and extracellular signal regulated protein kinase to activate inhibitor-kappa B kinase in human U87 astrocytoma cells. AB - Formyl peptide-receptor like-1 (FPRL-1) may possess critical roles in Alzheimer's diseases, chemotaxis and release of neurotoxins, possibly through its regulation of nuclear factor-kappaB (NFkappaB). Here we illustrate that activation of FPRL-1 in human U87 astrocytoma or Chinese hamster ovary cells stably expressing the receptor resulted in the phosphorylations of inhibitor-kappaB kinase (IKK), an onset kinase for NFkappaB signaling cascade. FPRL-1 selective hexapeptide Trp-Lys Tyr-Met-Val-Met (WKYMVM) promoted IKK phosphorylations in time- and dose dependent manners while pre-treatment of pertussis toxin abrogated the Galpha(i/o)-dependent stimulations. The FPRL-1-mediated IKK phosphorylation required extracellular signal-regulated protein kinase (ERK), phosphatidylinositol 3-kinase and cellular Src (c-Src), but not c-Jun N-terminal kinase and p38 mitogen-activated protein kinase. Despite its ability to mobilize Ca(2+), WKYMVM did not require Ca(2+) for the modulation of IKK phosphorylation. Activation of FPRL-1 also induced NFkappaB-driven luciferase expression. Interestingly, cholesterol depletion from plasma membrane by methyl-beta cyclodextrin abolished the FPRL-1-stimulated IKK phosphorylation, denoting the important role of lipid raft integrity in the FPRL-1 to IKK signaling. Furthermore, we demonstrated that in U87 cells, several signaling intermediates in the FPRL-1-IKK pathway including Galpha(i2), c-Src and ERK were constitutively localized at the raft microdomains. WKYMVM administration not only resulted in higher amount of ERK recruitment to the raft region, but also specifically stimulated raft-associated c-Src and ERK phosphorylations. Taken together, these results demonstrate that FPRL-1 is capable of activating NFkappaB signaling through IKK phosphorylation and this may serve as a useful therapeutical target for FPRL-1-related diseases. PMID- 17727630 TI - The differential effects of single or repeated restraint stress on kainic acid induced neuronal death in the hippocampal CA3 region: the role of glucocorticoid and various signal molecules. AB - The effect of stress mediators following the stress period and addition time is a controversial issue until now. Thus, we aim to clarify the differential effects of single restraint stress (SS) or repeated restraint stress (RS) on kainic acid (KA)-induced neuronal death especially as addressing not only the role of glucocorticoid (Gc) and its receptor but also the signal pathway leading to cAMP response element binding protein phosphorylation (pCREB) and its functional role during stress. In the present study, we found that although RS did not show any difference on serum Gc level and hippocampal Gc receptor level compared to SS, SS exacerbated KA-induced neuronal death in hippocampal CA3 region, but RS did not. Moreover, pre-treatment with RU 38486 (Gc receptor antagonist) abolished the effect of SS on KA-induced neuronal death without an effect on KA toxicity itself. Furthermore, RS aggravates KA-induced neuronal death when CREB phosphorylation was deprived by KN-93 (calcium/calmodulin-dependent protein kinase II inhibitor). However, other signal molecules inhibitors such as PD98059 (MEK1/2 inhibitor) and SP600125 (p-p38 inhibitor) have no effect on KA-induced neuronal death after RS although these signal molecule were increased during SS or RS. These findings suggest that pCREB expression via calcium/calmodulin dependent protein kinase II phosphorylation during RS comprise one of the balancers against Gc induced by stress. PMID- 17727631 TI - Vesicular release of glutamate mediates bidirectional signaling between astrocytes and neurons. AB - The major excitatory neurotransmitter in the CNS, glutamate, can be released exocytotically by neurons and astrocytes. Glutamate released from neurons can affect adjacent astrocytes by changing their intracellular Ca(2+) dynamics and, vice versa, glutamate released from astrocytes can cause a variety of responses in neurons such as: an elevation of [Ca(2+)](i), a slow inward current, an increase of excitability, modulation of synaptic transmission, synchronization of synaptic events, or some combination of these. This astrocyte-neuron signaling pathway might be a widespread phenomenon throughout the brain with astrocytes possessing the means to be active participants in many functions of the CNS. Thus, it appears that the vesicular release of glutamate can serve as a common denominator for two of the major cellular components of the CNS, astrocytes and neurons, in brain function. PMID- 17727629 TI - Peroxisome proliferator-activated receptor-alpha agonist fenofibrate regulates IL 12 family cytokine expression in the CNS: relevance to multiple sclerosis. AB - The interleukin-12 (IL-12) family of cytokines which includes IL-12, IL-23, and IL-27 play critical roles in T cell differentiation and are important modulators of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Previously, we demonstrated that peroxisome proliferator-activated receptor (PPAR) -alpha agonists suppress the development of EAE. The present studies demonstrated that the PPAR-alpha agonist fenofibrate inhibited the secretion of IL-12p40, IL-12p70 (p35/p40), IL-23 (p19/p40), and IL 27p28 by lipopolysaccharide-stimulated microglia. The cytokines interferon-gamma and tumor necrosis factor-alpha also stimulated IL-12 p40 and IL-27 p28 expression by microglia, which was suppressed by fenofibrate. Furthermore, fenofibrate inhibited microglial expression of CD14 which plays a critical role in TLR signaling, suggesting a mechanism by which this PPAR-alpha agonist regulates the production of these pro-inflammatory molecules. In addition, fenofibrate suppressed the secretion of IL-12p40, IL-23, and IL-27p28 by lipopolysaccharide-stimulated astrocytes. Importantly, fenofibrate suppression of EAE was associated with decreased expression of IL-12 family cytokine mRNAs as well as mRNAs encoding TLR4, CD14, and MyD88 known to play critical roles in MyD88-dependent TLR signaling. These novel observations suggest that PPAR-alpha agonists including fenofibrate may modulate the development of EAE, at least in part, by suppressing the production of IL-12 family cytokines and MyD88-dependent signaling. PMID- 17727632 TI - Nuclear factor-kappa B regulates seizure threshold and gene transcription following convulsant stimulation. AB - We evaluated a role for the nuclear factor-kappa B (NF-kappaB) pathway in the regulation of seizure susceptibility and transcriptional activation during prolonged, continuous seizures (status epilepticus). Using two functionally distinct NF-kappaB inhibitors we observed a decrease in latency to onset of kainate-induced seizures and status epilepticus. To assess NF-kappaB transcriptional activation, we evaluated inhibitor kappa B alpha (IkappaBalpha) and brain-derived neurotrophic factor (bdnf) gene targets. Inhibition of the NF kappaB signaling pathway significantly attenuated the increases in IkappaBalpha and bdnf mRNA levels that occurred during prolonged seizure activity, suggesting that the NF-kappaB pathway was involved in the up-regulation of these transcripts during status epilepticus. DNA-binding studies and chromatin immunoprecipitation assays using hippocampal extracts from animals with status epilepticus revealed that NF-kappaB subunits were associated with the candidate kappaB-binding elements within promoter 1 of the bdnf gene. The pattern of association was different for the p50 and p65 subunits supporting complex NF-kappaB modifications within promoter 1. In summary, our findings provide additional insights into the role of NF-kappaB transcriptional regulation in hippocampus following status epilepticus and suggest that NF-kappaB pathway activation contributes to seizure susceptibility. PMID- 17727634 TI - Juvenile nephropathy in 37 boxer dogs. AB - OBJECTIVES: The purpose of this study was to review and characterise the clinical presentation of young boxer dogs with chronic kidney disease referred to the authors' institutions. METHODS: Records were collected retrospectively from 37 boxer dogs, less than five years of age, which had presented with azotaemia, inappropriately low urine concentrating ability, and ultrasound or radiographic evidence of abnormal kidneys. RESULTS: Clinicopathological findings included azotaemia, hyperphosphataemia, anaemia, isosthenuria and proteinuria. Ultrasonographic findings included hyperechoic renal cortices, loss of corticomedullary junction definition, dilated pelves and irregularly shaped small kidneys. Renal histopathological findings included pericapsular and interstitial fibrosis, inflammatory cell infiltration, dilated tubules, sclerotic glomeruli and dystrophic calcification. Survival time of the dogs varied from zero to over five years after diagnosis. CLINICAL SIGNIFICANCE: This paper documents features of the presentation and progression of juvenile nephropathy in boxer dogs. While juvenile nephropathy has been reported in individual cases of boxer dogs previously, this is the first reported case series. PMID- 17727633 TI - Phosphorylation and activation of tryptophan hydroxylase 2: identification of serine-19 as the substrate site for calcium, calmodulin-dependent protein kinase II. AB - Tryptophan hydroxylase (TPH) is the initial and rate-limiting enzyme in the biosynthesis of serotonin. TPH was once thought to be a single-gene product but it is now known to exist in two isoforms. TPH1 is found in the periphery and pineal gland whereas TPH2 is expressed specifically in the CNS. Both TPH isoforms are known to be regulated by protein kinase-dependent phosphorylation and the sites of modification of TPH1 by protein kinase A have been identified. While TPH2 is activated by calcium, calmodulin-dependent protein kinase II (CaMKII), the sites at which this isoform is modified are not known. Treatment of wild-type TPH2 with CaMKII followed by mass spectrometry analysis revealed that the enzyme was activated and phosphorylated at a single site, serine-19. Mutagenesis of serine-19 to alanine did not alter the catalytic function of TPH2 but this mutant enzyme was neither activated nor phosphorylated by CaMKII. A phosphopeptide bracketing phosphoserine-19 in TPH2 was used as an antigen to generate polyclonal antibodies against phosphoserine-19. The antibodies are highly specific for phosphoserine-19 in TPH2. The antibodies do not react with wild-type TPH2 or TPH1 and they do not recognize phophoserine-58 or phosphoserine-260 in TPH1. These results establish that activation of TPH2 by CaMKII is mediated by phosphorylation of serine-19 within the regulatory domain of the enzyme. Production of a specific antibody against the CaMKII phosphorylation site in TPH2 represents a valuable tool to advance the study of the mechanisms regulating the function of this important enzyme. PMID- 17727635 TI - Neuroprotection and stroke: time for a compromise. AB - In April 2007, there existed a repertory of 286 trials concerned with acute ischemic stroke on the Stroke Trials Registry (http://www.strokecenter.org/trials/), of which 209 trials were considered as complete (with no evidence of patient benefit unless one considers the much hard fought for and modest results of the tPA studies). Among other questions arising from such failures, one can wonder whether the plethora of pharmacological agents that exhibited neuroprotective properties in pre-clinical studies were selected for clinical trials entirely based upon their experimental efficacy. This mini review will try to point out some of the weaknesses that could underline the failure of both researchers and clinicians involved in the field of stroke to obtain their ultimate goal--brain protection. PMID- 17727637 TI - Characterization of the adaptor protein ARH expression in the brain and ARH molecular interactions. AB - Previously, pA134 was identified as one of the mRNAs present in the squid giant axon. Comparative sequence analyses revealed that the pA134 gene product manifested significant similarity to the mammalian lipoprotein receptor adaptor protein also known as ARH (autosomal recessive hypercholesterolemia). ARH mRNA and protein displayed very similar pattern of expression throughout the mouse brain. Significant levels of expression were observed in cells with a predominantly neuronal profile in the cerebellum, brainstem, olfactory bulb, hippocampus, and cortex. A yeast two hybrid screen for ARH protein interactions in mouse brain identified the following binders: amyloid precursor-like protein 1, low density lipoprotein receptor-related protein (LRP) 1, LRP8, and GABA receptor-associated protein-like 1. The interactions of ARH with LRP1 and GABA receptor-associated protein-like 1 were subsequently verified by co immunoprecipitation of the protein complexes from transfected human embryonic kidney cells. The presence of ARH mRNA in axon of primary sympathetic neurons was established by RT-PCR analyses and confirmed by in situ hybridization. Taken together, our data suggest that ARH is a multifunctional protein whose spectrum of function in the brain goes beyond the traditionally known metabolism of lipoproteins, and that ARH may be locally synthesized in the axon. PMID- 17727636 TI - Single molecule profiling of tau gene expression in Alzheimer's disease. AB - Tau is a microtubule-associated protein that is important for establishing and maintaining neuronal morphology. In addition to its role in normal cells, tau protein is involved in many neurodegenerative diseases, e.g. Alzheimer's disease (AD) and frontotemporal dementia, as the main component of intraneuronal aggregates. Alternative splicing of tau gene in the brain can give rise to at least six protein variants. A causative role of skewed tau exon 10 inclusion has been defined in frontotemporal dementia; however, no link was established between the aberrant splicing of tau and AD. Here, we applied a single-molecule-based technology, polymerase colony or polony, to simultaneously monitor tau splicing variant and haplotype profile in sporadic AD and normal brains. We found that the coordinated expression of tau exons 2 and 10 is altered in AD. Additional investigations of cis and trans mechanisms of this observation revealed a decreased protein expression of a known tau splicing factor, htra2-beta-1 in AD, thereby implicating a trans mechanism. Our results demonstrate that dysregulation of combinatorial splicing might serve as a signature for aging-related diseases, and the polony assay could be widely adapted for the study of other tauopathies. Furthermore, splicing-based therapeutics is an emerging area of drug development, and a well-defined and quantitative assay for monitoring single-gene transcriptome will be relevant for such development. PMID- 17727638 TI - NMDA-mediated release of glutamate and GABA in the subthalamic nucleus is mediated by dopamine: an in vivo microdialysis study in rats. AB - The present study investigated the effects of N-methyl-D-aspartic acid.H2O (NMDA) on the dopamine, glutamate and GABA release in the subthalamic nucleus (STN) by using in vivo microdialysis in rats. NMDA (100 micromol/L) perfused through the microdialysis probe evoked an increase in extracellular dopamine in the STN of the intact rat of about 170%. This coincided with significant increases in both extracellular glutamate (350%) and GABA (250%). The effect of NMDA perfusion on neurotransmitter release at the level of the STN was completely abolished by co perfusion of the selective NMDA-receptor antagonist MK-801 (10 micromol/L), whereas subthalamic perfusion of MK-801 alone had no effect on extracellular neurotransmitter concentrations. Furthermore, NMDA induced increases in glutamate were abolished by both SCH23390 (8 micromol/L), a selective D1 antagonist, and remoxipride (4 micromol/L), a selective D2 antagonist. The NMDA induced increase in GABA was abolished by remoxipride but not by SCH23390. Perfusion of the STN with SCH23390 or remoxipride alone had no effect on extracellular neurotransmitter concentrations. The observed effects in intact animals depend on the nigral dopaminergic innervation, as dopamine denervation, by means of 6 hydroxydopamine lesioning of the substantia nigra, clearly abolished the effects of NMDA on neurotransmitter release at the level of the STN. Our work points to a complex interaction between dopamine, glutamate and GABA with a crucial role for dopamine at the level of the STN. PMID- 17727639 TI - Soluble oligomers from a non-disease related protein mimic Abeta-induced tau hyperphosphorylation and neurodegeneration. AB - Protein aggregation and amyloid accumulation in different tissues are associated with cellular dysfunction and toxicity in important human pathologies, including Alzheimer's disease and various forms of systemic amyloidosis. Soluble oligomers formed at the early stages of protein aggregation have been increasingly recognized as the main toxic species in amyloid diseases. To gain insight into the mechanisms of toxicity instigated by soluble protein oligomers, we have investigated the aggregation of hen egg white lysozyme (HEWL), a normally harmless protein. HEWL initially aggregates into beta-sheet rich, roughly spherical oligomers which appear to convert with time into protofibrils and mature amyloid fibrils. HEWL oligomers are potently neurotoxic to rat cortical neurons in culture, while mature amyloid fibrils are little or non-toxic. Interestingly, when added to cortical neuronal cultures HEWL oligomers induce tau hyperphosphorylation at epitopes that are characteristically phosphorylated in neurons exposed to soluble oligomers of the amyloid-beta peptide. Furthermore, injection of HEWL oligomers in the cerebral cortices of adult rats induces extensive neurodegeneration in different brain areas. These results show that soluble oligomers from a non-disease related protein can mimic specific neuronal pathologies thought to be induced by soluble amyloid-beta peptide oligomers in Alzheimer's disease and support the notion that amyloid oligomers from different proteins may share common structural determinants that would explain their generic cytotoxicities. PMID- 17727641 TI - Profile of cognitive impairment in chronic heart failure. AB - OBJECTIVES: To determine the frequency and pattern of cognitive dysfunction in outpatients with chronic congestive heart failure (CHF) and to identify the corresponding demographic and clinical correlates. DESIGN: Case-control study. SETTING: Outpatient clinic in a community hospital. PARTICIPANTS: Sixty-two outpatients with CHF, 53 controls diagnosed with cardiovascular disease uncomplicated by CHF (cardiac controls), and 42 healthy controls were investigated. MEASUREMENTS: Neuropsychological assessment included tests of mental speed, executive function, memory, language, and visuospatial function. Composite z-scores for five cognitive domains and mean z-score for overall cognitive performance were computed. The cutoff score to indicate cognitive impairment was defined as the overall healthy participants' cognitive z-score minus 2 standard deviations. Independent demographic and clinical predictors of cognitive impairment were identified using linear regression analysis. RESULTS: Patients with CHF showed a pattern of general cognitive impairment, including impairment of executive function, memory, language, mental speed, and attention. Twenty-five percent (P=.04) of patients with CHF were classified as cognitively impaired, compared with 15% of the cardiac controls and 4% of the healthy controls. Independent predictors of cognitive impairment in patients with CHF were estimated intelligence, New York Heart Association class, and presence of the apolipoprotein (Apo)E epsilon4 allele. CONCLUSION: Cognitive dysfunction is relatively common in patients with CHF, with deficits being most prominent in the domains of executive function, memory, language, and mental speed. Disease severity and ApoE genotype are likely to be important determinants for cognitive impairment in patients with chronic CHF. PMID- 17727642 TI - Attitudes and preferences of Korean-American older adults and caregivers on end of-life care. AB - A growing body of literature suggests that diverse attitudes toward the end of life exist across and within ethnic minority groups. This focus-group pilot study examined social and cultural factors influencing views of Korean-American older adults and caregivers on advance care planning and hospice care. A total of 20 older adults and 16 caregivers in west central Florida participated in one of four focus groups. This study found diverse attitudes among Korean Americans toward end-of-life care and cultural and structural barriers to advance care planning and hospice use. Older adults and caregivers both expressed a lack of knowledge about advance care planning and hospice and agreed that the family would make the final decision about the end-of-life care, while acknowledging the challenge of initiating communications about treatment preferences. They interpreted the Korean value of filial piety to support both curative and palliative treatment. The traditional norm of home death and importance of physician communication influenced preferences for hospice and advance care planning, respectively. Future outreach and education efforts should include development of culturally sensitive educational and communication tools and collaboration with ethnic community organizations and healthcare providers in the dissemination and education of these instruments. PMID- 17727643 TI - A comparative study of community- and nursing home-acquired empyema thoracis. AB - OBJECTIVES: To compare the clinical presentation, microbiological features, and outcomes of patients with community-acquired empyema (CAE) with those of patients with nursing home-acquired empyema (NHAE). DESIGN: A retrospective observational study. SETTING: Three tertiary care centers. PARTICIPANTS: One hundred fourteen patients admitted from the community and 55 patients transferred from nursing homes. MEASUREMENTS: Baseline sociodemographic information, activities of daily living, Charlson Comorbidity Index score, and clinica, and microbiologic data were obtained. Outcome was assessed at hospital discharge and 6 months postdischarge. RESULTS: Patients admitted from nursing homes had a delayed presentation, with dyspnea, weight loss, and anemia as the predominant manifestation. Patients with CAE presented more acutely, with fever, cough, and chest pain. Anaerobic organisms were more commonly isolated from patients with NHAE. The success rate of nonsurgical intervention was significantly lower for the NHAE patients than for the CAE group (39% vs 63; P=.01). In-hospital mortality was not significantly different between the two groups (NHAE, 18%; CAE, 8%; P=.09). In a Cox regression analysis, preadmission functional status (hazard ratio (HR)=1.26, 95% confidence interval (CI)=1.19-1.4; P<.001) and surgical intervention (HR=0.47, 95% CI=0.24-0.92; P=.03) were the only variables highly correlated with long-term outcome. CONCLUSION: Patients admitted with NHAE have distinctly different clinical and microbiological presentation from that of patients with CAE. Because of the delayed presentation in patients with NHAE, medical treatment alone may be associated with higher rate of failure. Surgical therapy should be considered for selected cases, with the aim of improving long term survival. PMID- 17727644 TI - Association between aspects of oral health-related quality of life and body mass index in community-dwelling older adults. AB - OBJECTIVES: To investigate whether underweight, normal-weight, overweight, and obese older adults differ in aspects of their oral health-related quality of life (OHRQoL). DESIGN: Cross-sectional study using a 54-item OHRQoL questionnaire. SETTING: Five counties in central Alabama: Jefferson and Tuscaloosa (urban), and Hale, Bibb, and Pickens (rural). PARTICIPANTS: The 291 subjects were recruited from participants in the University of Alabama at Birmingham Study of Aging, a longitudinal study of mobility. Participants ranged in age from 65 to 90 (60.5% women, 50.5% non-Hispanic white, and 50.5% rural). MEASUREMENTS: Participants completed an in-home interview about their OHRQoL using a 54-item questionnaire and were classified into four categories of body mass index (BMI) (<20.0 (underweight), 20.0-24.9 (normal), 25.0-29.9 (overweight), and >/=30.0 (obese)). Multivariate analyses were used to examine associations between BMI and OHRQoL, adjusting for age, race, sex, depression, education, perceived income, comorbidity score, life-space mobility, and physical activity level. RESULTS: The results suggested that a parabolic effect existed, with strongest associations occurring in the underweight and obese categories. With the normal BMI group as the reference group, obese participants were more likely to avoid eating foods they would like to eat, overweight participants were less likely to cook foods differently and reported better chewing ability, and underweight persons were more likely to limit foods they eat because of mouth dryness. CONCLUSION: Objective measures may not accurately reflect peoples' perceptions; therefore, OHRQoL determined according to response to subjective questions is important to properly assess a patient's overall health status. Older adults who are under- or overweight should be evaluated for oral health conditions that may affect their nutritional status. PMID- 17727646 TI - Prevalence of anemia in the nursing home: contribution of chronic kidney disease. AB - OBJECTIVES: To assess the independent contribution of chronic kidney disease (CKD) and age to anemia in older nursing home residents. DESIGN: Retrospective. SETTING: Skilled nursing facility. PARTICIPANTS: Nursing home residents with records in the Beverly Healthcare Data Warehouse who were admitted to a nursing home between January 1, 2002, and December 31, 2003; were alive as of January 31, 2004; and had hemoglobin and serum creatinine (SCr) values available for analysis. MEASUREMENTS: Prevalence of anemia (hemoglobin <13 g/dL for men and <12 g/dL for women) and CKD (estimated glomerular filtration rate <60 mL/min per 1.73 m(2), according to Modification of Diet in Renal Disease criteria) and the contribution of CKD and age to the prevalence of anemia. RESULTS: Six thousand two hundred resident records were analyzed (70% female, 85% Caucasian). Overall, 59.6% of residents were anemic, and 43.1% had CKD, and residents with CKD were more likely to have anemia (64.9% with vs 55.7% without CKD; odds ratio (OR)=1.47, 95% confidence interval (CI)=1.33-1.63). Although older age was associated with lower hemoglobin values primarily in residents without CKD (Spearman rank correlation coefficient (r)=-0.10, P<.001), age had no association with hemoglobin in CKD (Spearman r=0.01, P=.60). The greater risk of anemia in the presence of CKD persisted in each age category (OR=2.07, 95% CI=1.53-2.80, aged 65-74; OR=1.44, 95% CI=1.21-1.70, aged 75-84; and OR=1.35, 95% CI=1.15-1.57, aged > or =85). CONCLUSION: Overall, these results suggest that CKD contributes more strongly than older age to the high prevalence of anemia in older nursing home residents. PMID- 17727645 TI - Three-year change in inflammatory markers in elderly people and mortality: the Invecchiare in Chianti study. AB - OBJECTIVES: To describe changes in interleukin-6 (IL-6) and C-reactive protein (CRP) and to determine how changes are related to mortality in elderly people. DESIGN: Prospective cohort study. SETTING: Two communities in the Tuscany region of Italy. PARTICIPANTS: Randomly selected residents aged 65 and older who participated in the first two waves of data collection (N=736). MEASUREMENTS: Two serum measurements of IL-6 and CRP taken 3 years apart. Mortality was observed for the 3 years after the second measurement; 79 deaths were observed in 2,079 person-years. RESULTS: Correlations indicated marginal to moderate stability in IL-6 and CRP, with clinical categories remaining relatively stable over time. Baseline levels were not related to mortality between follow-up Years 3 and 6, but increases in IL-6 and CRP predicted 3- to 6-year mortality. Controlling for follow-up IL-6 and CRP attenuated the relationship between inflammatory changes and mortality, but increases in CRP continued to increase odds of mortality. After controlling for sociodemographic characteristics, biological risk factors, health behaviors, and disease at both times, increases in CRP, but not IL-6, were related to mortality. Odds of death were more than three times as great in subjects in whom any CRP increase was observed (odds ratio=3.10, 95% confidence interval=1.25-7.68) as in subjects with stable or declining CRP. CONCLUSION: CRP and IL-6 levels within individuals vary over time, and increases in CRP are associated with greater mortality risk. Three-year changes in inflammatory markers are better predictors of mortality than baseline measures. PMID- 17727647 TI - Symptom experience of dying long-term care residents. AB - OBJECTIVES: To describe the end-of-life symptoms of nursing home (NH) and residential care/assisted living (RC/AL) residents, compare staff and family symptom ratings, and compare how staff assess pain and dyspnea for cognitively impaired and cognitively intact residents. DESIGN: After-death interviews. SETTING: Stratified random sample of 230 long-term care facilities in four states. PARTICIPANTS: Staff (n=674) and family (n=446) caregivers for dying residents. MEASUREMENTS: Interview items measured frequency and severity of physical symptoms, effectiveness of treatment, recommendations to improve care, and staff report of assessment. RESULTS: Decedents' median age was 85, 89% were white, and 77% were cognitively impaired. In their last month of life, 47% had pain, 48% dyspnea, 90% problems with cleanliness, and 72% symptoms affecting intake. Problems with cleanliness, intake, and overall symptom burden were worse for decedents in NHs than for those in RC/AL. Treatment for pain and dyspnea was rated very effective for only half of decedents. For a subset of residents with both staff and family interviews (n=331), overall ratings of care were similar, although agreement in paired analyses was modest (kappa=-0.043-0.425). Staff relied on nonverbal expressions to assess dyspnea but not pain. Both groups of caregivers recommended improved application of treatment and increased staffing to improve care. CONCLUSION: In NHs and RC/AL, dying residents have high rates of physical symptoms and need for more-effective palliation of symptoms near the end of life. PMID- 17727649 TI - Diagnosing and treating breast cancer in elderly women: a call for improved understanding. AB - Breast cancer is the most common nondermatological malignancy in women, and the incidence increases with age until the eighth decade. Breast cancer pathology and biology appear to be different in elderly patients than in younger ones, and therefore treatment recommendations cannot be generalized from one group to the other. Most elderly women can tolerate breast cancer surgery without significant complications and should be offered a definitive surgical procedure. Improved mechanisms to predict which patients will tolerate and benefit from various therapies are under development. Because most breast cancers in the elderly are hormone responsive, hormonal therapy remains the mainstay of systemic treatment in the adjuvant and metastatic settings. Chemotherapy can be used in elderly women, but treatment decisions must be individualized based upon risk-benefit analyses. Elder-specific studies are underway to identify the most-efficacious and best-tolerated therapies for breast cancer in this population. Primary care physicians must be aware of these issues to provide adequate counseling and care to these patients. PMID- 17727648 TI - Treatment of dementia in community-dwelling and institutionalized medicare beneficiaries. AB - OBJECTIVES: To establish nationally representative estimates of the use of agents to treat Alzheimer's disease and related dementias (ADRDs) and related behavioral symptoms in Medicare beneficiaries and to describe medication use according to residential status and other patient characteristics. DESIGN: Cross-sectional prevalence study. SETTING: Community and various long-term care (LTC) settings. PARTICIPANTS: Twelve thousand six hundred ninety-seven beneficiaries from the 2002 Medicare Current Beneficiary Survey (MCBS), of whom 11,593 were community dwelling and 1,104 resided in various LTC settings. MEASUREMENTS: ADRDs were identified according to International Classification of Diseases, Ninth Revision, codes in Medicare claims and self- and proxy reports. Medication use was derived from self-reports (community) and extracts of facility medication administration records (LTC). RESULTS: In 2002, an estimated 3.4 million Medicare beneficiaries were diagnosed with ADRDs (8.1%), of whom 58.9% resided in the community (prevalence rate=5.1%) and 41.1% resided in LTC facilities (prevalence rate=57.2%). Use of antidementia drugs was similar across settings, with 24.7% of subjects with dementia in the community and 26.3% of those in LTC receiving prescriptions for donepezil, galantamine, or rivastigmine. Use of haloperidol was comparable (and low) in both settings. Use of atypical antipsychotics, especially risperidone, olanzapine, and quetiapine, was much higher in LTC residents (21.0%, 11.9%, and 7.1%, respectively) than in the community (5.1%, 4.0%, and 2.3%). CONCLUSION: The prevalence of ADRDs in LTC settings is much larger than in the community, but there is little difference in the proportions receiving antidementia drugs, although LTC residents are more likely to be treated with atypical antipsychotics (risperidone, olanzapine, and quetiapine), presumably for behavioral symptoms. PMID- 17727650 TI - Effects of free radical scavenger on acute liver injury induced by d galactosamine and lipopolysaccharide in rats. AB - AIM: Acute severe liver injury still has a high mortality rate. Acute liver injury induced by a coadministration of d-galactosamine (GalN) and lipopolysaccharide (LPS) is an experimental model of fulminant hepatitis in rats. Our aim is to investigate the effects of free radical scavenger on the injury induced by GalN/LPS in rats. METHODS: Free radical scavenger edaravone (3-methyl 1-phenyl-2-pyrazolin-5-one) was twice injected into rats 5 min before and 60 min after the GalN/LPS injection. Liver injury was biochemically and histologically assessed. The survival rate was examined 72 h after the intoxication. RESULTS: In the GalN/LPS-treated rats, a marked elevation in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels was observed. On the other hand, edaravone significantly inhibited the elevation in serum AST and ALT levels. The efficacy of edaravone was also confirmedby histological analysis. Edaravone lowered the levels of proinflammatory cytokines TNF-alpha mRNA and interleukin-6 mRNA expression, antioxidative enzyme heme oxygenase-1 protein and myeloperoxidase activity, a marker of neutrophil infiltration, in rat livers. In addition, edaravone reduced the mortality rate in GalN/LPS-treated rats as compared to the rats without edaravone treatment. CONCLUSIONS: Free radical scavenger edaravone effectively ameliorated the liver injury induced by the GalN/LPS administration in rats, not only by attenuating oxidative stress, but also by reducing the expression of proinflammatory cytokines. PMID- 17727651 TI - Iron stress increases Bordetella pertussis mucin-binding capacity and attachment to respiratory epithelial cells. AB - Whooping cough is a reemerging infectious disease of the respiratory tract caused by Bordetella pertussis. The incomplete understanding of the molecular mechanisms of host colonization hampers the efforts to control this disease. Among the environmental factors that commonly determine the bacterial phenotype, the concentration of essential nutrients is of particular importance. Iron, a crucial and scarce nutrient in the natural environment of B. pertussis, has been found to induce substantial phenotypic changes in this pathogen. However, the relevance of this phenotype for the interaction with host cells was never investigated. Using an in vitro model for bacterial attachment, it was shown that the attachment capacity of B. pertussis to epithelial respiratory cells is enhanced under iron stress conditions. Attachment is mediated by iron-induced surface-exposed proteins with sialic acid-binding capacity. The results further suggest that some of these iron-induced surface-associated proteins are immunogenic and may represent attractive vaccine candidates. PMID- 17727652 TI - Prevotella intermedia lipopolysaccharide stimulates release of tumor necrosis factor-alpha through mitogen-activated protein kinase signaling pathways in monocyte-derived macrophages. AB - The purpose of this study was to investigate the effects of lipopolysaccharide from Prevotella intermedia, a major cause of inflammatory periodontal disease, on the production of tumor necrosis factor (TNF)-alpha and the expression of TNF alpha mRNA in differentiated THP-1 cells, a human monocytic cell line. The potential involvement of the three main mitogen-activated protein kinase (MAPK) signaling pathways in the induction of TNF-alpha production was also investigated. Lipopolysaccharide from P. intermedia ATCC 25611 was prepared by the standard hot phenol-water method. THP-1 cells were incubated in the medium supplemented with phorbol myristate acetate to induce differentiation into macrophage-like cells. It was found that P. intermedia lipopolysaccharide can induce TNF-alpha mRNA expression and stimulate the release of TNF-alpha in differentiated THP-1 cells without additional stimuli. Treatment of the cells with P. intermedia lipopolysaccharide resulted in a simultaneous activation of three MAPKs [extracellular signal-related kinase 1/2 (ERK1/2), c-Jun N-terminal kinase 1/2 (JNK1/2) and p38]. Pretreatment of the cells with MAPK inhibitors effectively suppressed P. intermedia lipopolysaccharide-induced TNF-alpha production without affecting the expression of TNF-alpha mRNA. These data thus provided good evidence that the MAPK signaling pathways are required for the regulation of P. intermedia lipopolysaccharide-induced TNF-alpha synthesis at the level of translation more than at the transcriptional level. PMID- 17727653 TI - Variation of the expression of Mycobacterium tuberculosis ppe44 gene among clinical isolates. AB - PPE44 is a member of the Mycobacterium tuberculosis PPE proteins, a polymorphic family of 69 glycine-rich proteins that predictively represent a source of antigenic variation. The genetic diversity of gene ppe44 among clinical isolates has been studied. No genomic polymorphism of ppe44 was found by a PCR-restriction fragment length polymorphism assay using three restriction enzymes. Nucleotide sequencing of gene ppe44 of a number of isolates, selected to represent the major phylogenetic lineages of M. tuberculosis, showed no nucleotide substitution, with the exception of isolates of the Beijing genotype. These findings indicate that gene ppe44 is basically conserved among M. tuberculosis strains. The expression of gene ppe44 was then determined at the transcriptional level by a real-time reverse transcriptase PCR assay. Extremely high quantitative variations in ppe44 expression were found among the isolates; ppe44 expression of the Beijing strains was significantly higher than the non-Beijing strains. To test whether differential expression of gene ppe44 has the potential to provide a dynamic antigen display, antibodies to PPE44 were titered in the sera of M. tuberculosis infected subjects. Variation of antibody response to PPE44 was found with regard to both antibody titers and the proportion of responding subjects. These results indicate that the differential expression of genes ppe could influence the host's immune responsiveness, thus having implications in the immunopathogenesis of tuberculosis. PMID- 17727654 TI - Variation in the WBC differential count and other factors associated with reporting of herpes labialis: a population-based study of adults. AB - Reactivation of latent herpes virus has been linked to triggers of mild immunosupression, such as stress or UV-exposure. Despite having predictive value in severe immunodeficiency, the white blood cell (WBC) differential count has not been examined in relation to risk of herpes reactivation in population studies. The WBC differential count and other risk factors for herpes labialis were examined in 5687 adults (ages 18-64) from the Third National Health and Nutrition Examination Survey, who had WBC 3.5-11 x 10(6) cells mL(-1) and reported no acute infections in the past month. The association between self-reported herpes labialis in the past year and the WBC differential count was modeled, adjusting for age, sex, race/ethnicity, education, smoking, upper respiratory infections (URI), and HSV-1 antibodies. Herpes labialis was significantly associated with white race/ethnicity, being a nonsmoker, and frequent URI. Compared with the highest quartile, being in the lowest quartile of granulocytes was associated with herpes labialis, adjusted odds ratio=1.82 (95% confidence interval 1.20, 2.28). At the same time, there was a trend towards an inverse association of lower lymphocyte count and herpes labialis. These findings suggest that moderate differences in the WBC differential count are related to reactivation of HSV-1. Prospective studies may help to show whether such differences indicate susceptibility to loss of latency or represent a consequence of reactivated infection. PMID- 17727656 TI - Chlamydia pneumoniae infection of aortic smooth muscle cells reduces platelet derived growth factor receptor-beta expression. AB - Chlamydia pneumoniae infection may play a role in the pathogenesis of atherosclerosis. In this study, an oligonucleotide microarray was utilized to examine the transcriptional response of human aortic smooth muscle cells (AoSMC) to C. pneumoniae infection. Alteration of mRNA expression in 71 out of 780 genes was detected at 24 h after infection. Among the down-regulated genes, platelet derived growth factor receptor-beta (PDGFR-beta) was identified as a target for further analysis because the PDGF system is involved in the fibroproliferative response of SMC in atherogenesis. Reverse transcriptase PCR analysis demonstrated that C. pneumoniae inhibits the up-regulation of PDGFR-beta mRNA occurring in AoSMC after mock infection. PDGFR-beta protein synthesis was examined by immunoblotting and fluorescence-activated cell sorting. Compared with mock infected cells, the amount of receptor protein was reduced at 24, 48, and 72 h after infection. Diminished PDGFR-beta synthesis in infected cultures was accompanied by the suppression of AoSMC growth following PDGF-BB stimulation. The interference of C. pneumoniae with PDGFR-beta expression may result in decreased SMC proliferation in atherosclerotic plaques, thereby affecting the development and stability of advanced lesions. PMID- 17727655 TI - A role for natural killer cells in intestinal inflammation caused by infection with Salmonella enterica serovar Typhimurium. AB - Acute gastroenteritis caused by Salmonella infection is a significant public health problem. Using a mouse model of this condition, the authors demonstrated previously that the cytokine gamma interferon (IFN-gamma) is required for a normal intestinal inflammatory response to the pathogen. In the present study, these experiments are extended to show that natural killer (NK) cells constitute an early source of intestinal IFN-gamma during Salmonella infection, and that these cells have a significant impact on intestinal inflammation. It was found that infection of mice with Salmonella increased both intestinal IFN-gamma production and the numbers of NK cells in the intestine and mesenteric lymph nodes. NK cells, along with other types of lymphocytes, produced IFN-gamma in response to the bacteria in vitro, while antibody-mediated depletion of NK cells in vivo resulted in a significant reduction in Salmonella-induced intestinal IFN gamma expression. In a mouse strain lacking NK cells and T and B lymphocytes, intestinal production of IFN-gamma and Salmonella-induced intestinal inflammation were both significantly decreased compared with a strain deficient only in T and B cells. The authors' observations point to an important function for NK cells and NK-derived IFN-gamma in regulating the intestinal inflammatory response to Salmonella. PMID- 17727657 TI - Increased tolerance of Staphylococcus aureus to vancomycin in viscous media. AB - The increased viscosity observed in biofilms, adherent communities of bacterial cells embedded in a polymeric matrix, was hypothesized to induce increased tolerance of bacteria to antibiotics. To test this concept, planktonic Staphylococcus aureus cells were grown and exposed to vancomycin in media brought to specific viscosities in order to mimic the biofilm extracellular polymeric matrix. A viscous environment was observed to decrease the vancomycin susceptibility of planktonic S. aureus to levels seen for biofilms. Both planktonic S. aureus at a viscosity of 100 mPa s and staphylococcal biofilms were able to survive at >500 times the levels of the antibiotic effective against planktonic populations in standard medium. Time-dependent and dose-dependent viability curves revealed that more than one mechanism was involved in high S. aureus tolerance to vancomycin in viscous media. Increased viscosity affects antibiotic susceptibility by reducing diffusion and the mass transfer rate; this mechanism alone, however, cannot explain the increased tolerance demonstrated by S. aureus in viscous media, suggesting that viscosity may also alter the phenotype of the planktonic bacteria to one more resistant to antimicrobials, as seen in biofilms. However, these latter changes are not yet understood and will require further study. PMID- 17727658 TI - Monitoring of Saccharomyces and Hanseniaspora populations during alcoholic fermentation by real-time quantitative PCR. AB - Real-time, or quantitative, PCR (QPCR) was developed for the rapid quantification of two of the most important yeast groups in alcoholic fermentation (Saccharomyces spp. and Hanseniaspora spp.). Specific primers were designed from the region spanning the internal transcribed spacer 2 (ITS2) and the 5.8S rRNA gene. To confirm the specificity of these primers, they were tested with different yeast species, acetic acid bacteria and lactic acid bacteria. The designed primers only amplified for the intended group of species and none of the PCR assays was positive for any other wine microorganisms. This technique was performed on reference yeast strains from pure cultures and validated with both artificially contaminated wines and real wine fermentation samples. To determine the effectiveness of the technique, the QPCR results were compared with those obtained by plating. The design of new primers for other important wine yeast species will enable to monitor yeast diversity during industrial wine fermentation and to detect the main spoilage yeasts in wine. PMID- 17727659 TI - Impact of systems biology on metabolic engineering of Saccharomyces cerevisiae. AB - Industrial biotechnology is a rapidly growing field. With the increasing shift towards a bio-based economy, there is rising demand for developing efficient cell factories that can produce fuels, chemicals, pharmaceuticals, materials, nutraceuticals, and even food ingredients. The yeast Saccharomyces cerevisiae is extremely well suited for this objective. As one of the most intensely studied eukaryotic model organisms, a rich density of knowledge detailing its genetics, biochemistry, physiology, and large-scale fermentation performance can be capitalized upon to enable a substantial increase in the industrial application of this yeast. Developments in genomics and high-throughput systems biology tools are enhancing one's ability to rapidly characterize cellular behaviour, which is valuable in the field of metabolic engineering where strain characterization is often the bottleneck in strain development programmes. Here, the impact of systems biology on metabolic engineering is reviewed and perspectives on the role of systems biology in the design of cell factories are given. PMID- 17727660 TI - The strange case of a biofilm-forming strain of Pichia fermentans, which controls Monilinia brown rot on apple but is pathogenic on peach fruit. AB - A biofilm-forming strain of Pichia fermentans proved to be most effective in controlling brown rot on apple fruit when coinoculated into artificial wounds with a phytopathogenic isolate of Monilinia fructicola. Culture filtrates and autoclaved cells had no significant influence on the disease. When sprayed onto the apple fruit surface, this yeast formed a thin biofilm but failed to colonize the underlying tissues. When inoculated into wounds artificially inflicted to peach fruit or when sprayed onto the surface of peach fruit, the same strain showed an unexpected pathogenic behaviour, causing rapid decay of fruit tissues even in the absence of M. fructicola. Both optical and scanning electron microscopy were used to evaluate the pattern of fruit tissue colonization by P. fermentans. While on apple surface and within the apple wound the antagonist retained its yeast-like shape, colonization of peach fruit tissue was always characterized by a transition from budding growth to pseudohyphal growth. These results suggest that pseudohyphal growth plays a major role in governing the potential pathogenicity of P. fermentans, further emphasizing the importance of a thorough risk assessment for the safe use of any novel biocontrol agent. PMID- 17727661 TI - Partial conservation of functions between eukaryotic frataxin and the Escherichia coli frataxin homolog CyaY. AB - Frataxin is a mitochondrial protein structurally conserved from bacteria to humans. Eukaryotic frataxins are known to be involved in the maintenance of mitochondrial iron balance via roles in iron delivery and iron detoxification. The prokaryotic frataxin homolog, CyaY, has been shown to bind and donate iron for the assembly of [2Fe-2S] clusters in vitro. However, in contrast to the severe phenotypes associated with the partial or complete loss of frataxin in humans and other eukaryotes, deletion of the cyaY gene does not cause any obvious alteration of iron balance in bacterial cells, an effect that probably reflects functional redundancy between CyaY and other bacterial proteins. To study CyaY function in a nonredundant setting, we have expressed a mitochondria-targeted form of CyaY in a Saccharomyces cerevisiae strain depleted of the endogenous yeast frataxin protein (yfh1Delta). We show that in this strain CyaY complements to a large extent the loss of iron-sulfur cluster enzyme activities and heme synthesis, and thereby maintains a nearly normal respiratory growth. In addition, CyaY effectively protects yfh1Delta from oxidative damage during treatment with hydrogen peroxide but is less efficient in detoxifying excess labile iron during aerobic growth. PMID- 17727662 TI - The large N-terminal domain of Cdc25 protein of the yeast Saccharomyces cerevisiae is required for glucose-induced Ras2 activation. AB - The Saccharomyces cerevisiae CDC25 gene encodes a guanine nucleotide exchange factor for Ras proteins whose catalytic domain is highly homologous to Ras guanine nucleotide exchange factors from higher eukaryotes. In this study, glucose-induced Ras activation and cAMP response were investigated in mutants lacking the N-terminal domain of Cdc25 or where the entire CDC25 coding sequence was substituted by an expression cassette for a mammalian guanine nucleotide exchange factor catalytic domain. Our results suggest that an unregulated, low Ras guanine nucleotide exchange factor activity allows a normal glucose-induced cAMP signal that appears to be mediated mainly by the Gpr1/Gpa2 system, but it was not enough to sustain the glucose-induced increase of Ras2-GTP normally observed in a wild-type strain. PMID- 17727663 TI - Magnetic resonance imaging of the brain used to detect early post-partum activation of multiple sclerosis. AB - Post-partum relapses are a frequent phenomenon in multiple sclerosis (MS). The purpose of this study was to evaluate the timing and extent of new or growing T2 lesions after delivery in a cohort of Finnish MS patients. In addition to serial magnetic resonance imaging (MRI), the patients were followed up clinically with determination of relapse rate and expanded disability status scale. The annualized relapse rate was decreased during the last trimester of pregnancy [mean 0.14, standard deviation (SD) 0.14] when compared with the time before pregnancy (mean 0.64, SD 0.14; P = 0.04) and to time post-partum (mean 1.50, SD 0.45; P = 0.0002). New or enlarging lesions were detected in the post-partum images in 14 of 28 patients. Gadolinium-enhancing lesions in post-partum MRI were present in eight of 13 patients. There was a significant increase in the number of T2-lesions (P = 0.0009), in the total volume of MS-lesions measured from fluid attenuated inversion recovery images (P = 0.0126) and in the number of diffusion weighted imaging hyperintense lesions (P = 0.0098) in the post-partum images. The clinical results support the earlier findings of decreased disease activity in late pregnancy. The clinical and MRI findings indicate that post-partum activation is an early and common phenomenon amongst mothers with MS. PMID- 17727664 TI - Effect of single mannitol bolus in intracerebral hemorrhage. AB - Because of existing controversy about use of mannitol in intracerebral hemorrhage (ICH) this open exploratory trial with blinded outcome assessment of single mannitol bolus in ICH was undertaken. CT proven primary supratentorial ICH patients having midline shift of > or =3 mm were randomized into 20% mannitol (1.5 g/kg) and control groups. Clinical evaluation included Glasgow coma scale (GCS) score, Canadian Neurological scale (CNS) score, pupils, breathing, extensor posturing and contra-lateral pyramidal signs. On cranial MRI horizontal (HS), superior sagittal sinus to pontomesencephalic junction (SSS-PMJ) distance and edema hematoma complex were measured. Twelve patients each were in mannitol and control groups. The age, sex, GCS score, CNS score, pupillary asymmetry, contra lateral pyramidal signs, HS and SSS-PMJ distance in mannitol and control groups did not differ significantly. Mannitol infusion resulted clinical improvement in five patients, which lasted for 30-60 min. HS and SSS-PMJ distance in mannitol and control groups did not change at 30 or 60 min from the baseline. The change in HS and SSS-PMJ distance were also not significantly different between the two groups both at 30 and 60 min. Mannitol led to transient clinical improvement in five patients without significant reduction in HS or SSS-PMJ distance at 30 and 60 min. PMID- 17727665 TI - Environmental fluctuations can stabilize food web dynamics by increasing synchrony. AB - Natural food webs are species-rich, but classical theory suggests that they should be unstable and extinction-prone. Asynchronous fluctuations in the densities of competing consumers can stabilize food web dynamics in constant environments. However, environmental fluctuations often synchronize dynamics in nature. Using the same 'diamond-shape' food web model first used to demonstrate the stabilizing effects of asynchrony in constant environments, we show that weak to-moderate environmentally induced fluctuations in consumer mortality rates stabilize food webs while disrupting asynchrony. Synchrony actually promotes stability because: (i) synchronous declines in consumer density reduce the maximum abundance of top predators and (ii) resource competition quickly converts synchronous increases in consumer density into synchronous declines. These results are robust to details of food web topology and the implementation of environmental fluctuations. The fluctuation strengths that enhance stability are within the range experienced naturally by many species, suggesting that stabilization via environmental fluctuations is a realistic possibility. PMID- 17727666 TI - Utility of magnetoencephalography in the evaluation of recurrent seizures after epilepsy surgery. AB - PURPOSE: To study the role of magnetoencephalography (MEG) in the surgical evaluation of children with recurrent seizures after epilepsy surgery. METHODS: We studied 17 children with recurrent seizures after epilepsy surgery using interictal and ictal scalp EEG, intracranial video EEG (IVEEG), MRI, and MEG. We analyzed the location and distribution of MEG spike sources (MEGSSs) and the relationship of MEGSSs to the margins of previous resections and surgical outcome. RESULTS: Clustered MEGSSs occurred at the margins of previous resections within two contiguous gyri in 10 patients (group A), extended spatially from a margin by < or =3 cm in three patients (group B), and were remote from a resection margin by >3 cm in six patients (group C). Two patients had concomitant group A and C clusters. Thirteen patients underwent second surgeries. IVEEG was used in four patients. Six of seven patients with group A MEGSS clusters did not require IVEEG for second surgeries. Follow-up periods ranged from 0.6 to 4.3 years (mean: 2.6 years). Eleven children, including eight who became seizure free, achieved Engel class I or II. CONCLUSION: Our data demonstrate the utility of MEG for evaluating patients with recurrent seizures after epilepsy surgery. Specific MEGSS cluster patterns delineate epileptogenic zones. Removing cluster regions adjacent to the margins of previous resections, in addition to removing recurrent lesions, achieves favorable surgical outcome. Cluster location and extent identify which patients require IVEEG, potentially eliminating IVEEG for some. Patients with remotely located clusters require IVEEG for accurate assessment and localization of the entire epileptogenic zone. PMID- 17727668 TI - Epileptic automatisms in the criminal courts: 13 cases tried in England and Wales between 1975 and 2001. AB - OBJECTIVES: To explore the relationship of epilepsy and criminal behavior. METHODS: Case series based on all criminal cases found "not guilty by reason of insanity" (NGRI) because of epilepsy in England and Wales between 1975 and 2001. Data were extracted from medico-legal reports held by the Mental Health Unit at the Home Office and the Department for Constitutional Affairs in London, UK. RESULTS: Thirteen cases were identified, accounting for 7.3% of all verdicts of NGRI. Charges included murder (1), attempted murder (1) assault (7), arson (2), abduction/kidnapping (3), and burglary (1). Of the defendants, 92.3% were male, 76.9% had neuropsychological impairments, 84.6%% had psychiatric comorbidity, 92.3% were unemployed at the time of the offence, and 69.2% had been convicted of criminal offences previously. Eight of 10 defendants treated with antiepileptic drugs were complying poorly with medication. A total of 61.5% offenses were committed in a state of alcohol intoxication. Psychotic symptoms may have been present when the offense was committed in 52.8% of cases. Over two-thirds of offenses probably occurred during the postictal period. CONCLUSIONS: This case series suggests that it is exceptional for epileptic seizures to cause criminal acts or omissions. The relatively low standard of proof required means that some of cases found NGRI on account of epilepsy were not actually related to seizures. There were no definite examples of ictal criminal behavior. Most offenses related to seizures are likely to have occurred in the postictal phase. PMID- 17727669 TI - Association between particular polymorphic residues on apical membrane antigen 1 (AMA-1) and platelet levels in patients with vivax malaria. AB - Apical membrane antigen 1 (AMA-1) is an immunogenic type 1 integral membrane protein, present in all Plasmodium spp., that probably has a role in the initiation of the invasion process of the erythrocyte. The DNA sequence of variable domain I of the Plasmodium vivax ama1 gene was sequenced in Brazilian isolates obtained from thrombocytopenic patients (n = 32) and patients with normal platelet counts (n = 22). There was a significant negative correlation between parasite density and platelet counts. It was concluded that there is an additional effect of sequence on platelet counts. The presence of amino-acid residues Y(193) and S(210) was associated significantly with normal platelet counts in P. vivax malaria, independent of the level of parasitaemia (p <0.0001). These data have implications for AMA-1-based vaccine design and suggest the possible use of this molecule as a marker of morbidity. PMID- 17727667 TI - Mechanisms of epileptogenesis in tuberous sclerosis complex and related malformations of cortical development with abnormal glioneuronal proliferation. AB - Malformations of cortical development (MCDs) are increasingly recognized as causes of medically intractable epilepsy. In order to develop more effective, rational therapies for refractory epilepsy related to MCDs, it is important to achieve a better understanding of the underlying mechanisms of epileptogenesis, but this is complicated by the wide variety of different radiographic, histopathological, and molecular features of these disorders. A subset of MCDs share a number of characteristic cellular and molecular abnormalities due to early defects in neuronal and glial proliferation and differentiation and have a particularly high incidence of epilepsy, suggesting that this category of MCDs with abnormal glioneuronal proliferation may also share a common set of primary mechanisms of epileptogenesis. This review critically analyzes both clinical and basic science evidence for overlapping mechanisms of epileptogenesis in this group of disorders, focusing on tuberous sclerosis complex, focal cortical dysplasia with balloon cells, and gangliogliomas. Specifically, the role of lesional versus perilesional regions, circuit versus cellular/molecular defects, and nonneuronal factors, such as astrocytes, in contributing to epileptogenesis in these MCDs is examined. An improved understanding of these various factors involved in epileptogenesis has direct clinical implications for optimizing current treatments or developing novel therapeutic approaches for epilepsy in these disorders. PMID- 17727670 TI - Antimicrobial susceptibility testing of Mycobacterium tuberculosis (EUCAST document E.DEF 8.1)--report of the Subcommittee on Antimicrobial Susceptibility Testing of Mycobacterium tuberculosis of the European Committee for Antimicrobial Susceptibility Testing (EUCAST) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). AB - This review describes the methods available for drug susceptibility testing of Mycobacterium tuberculosis. The methods have been developed over several decades and are restricted to specialised centres in most European countries, as they are technically demanding, require appropriate isolation facilities and can be difficult to interpret. The absolute concentration, resistance ratio and proportion methods can all give accurate results, provided that they are carefully quality-controlled and standardised. Automated rapid culture and molecular methods have been evaluated at large reference centres and in multicentre collaborations, and perform well for testing susceptibility to most first- and second-line anti-tuberculosis drugs. Accuracy is more important than rapid testing, and this is most reliably achieved if drug susceptibility tests are done in a small number of well-equipped, experienced laboratories that participate and perform well in an international drug susceptibility testing quality assessment scheme. The WHO Supranational Laboratory Quality Control Network offers a global scheme that assesses the ability of participating laboratories to identify isoniazid, rifampicin, ethambutol and streptomycin resistance. Second-line drug resistance testing is currently being standardised, and such testing should only be performed at the national reference laboratories in western and central European countries because of the relatively small number of cases and the concomitant difficulty of maintaining testing proficiency in multiple centres performing small numbers of tests. There is a need to expand international external quality assessment to include second-line drug susceptibility testing. PMID- 17727671 TI - Role of superantigenic strains in the prognosis of community-acquired methicillin susceptible Staphylococcus aureus bacteraemia. AB - Methicillin-susceptible Staphylococcus aureus (MSSA) strains can produce superantigenic toxins that may trigger a massive release of pro-inflammatory cytokines, which are involved in the onset of septic shock. This 1-year prospective pilot study assessed the role of the production of superantigenic toxins in the outcome of immunocompetent patients hospitalised for community acquired MSSA bacteraemia. Thirty-seven patients were enrolled, of whom 14 died in hospital. Fourteen patients had septic shock, and the mortality rate in this subgroup was 56%. Twenty-seven (73%) isolates produced at least one superantigenic toxin, but this did not influence the rate of occurrence of septic shock or death. PMID- 17727672 TI - The inulin hydrogen breath test accurately reflects orocaecal transit time. AB - BACKGROUND: The lactose[(13)C]ureide breath test ((13)C-LUBT) has been validated and established as a reliable, non-invasive test for the assessment of orocaecal transit time (OCTT). More recently, small studies have demonstrated that inulin could be an alternative substrate for H(2)-based breath testing of the small bowel transit (H(2)-INBT). We compared the performance of the H(2)-INBT with the (13)C-LUBT in an appropriate number of participants, determined by sample-size calculation. DESIGN: Twenty-nine people underwent a combined (13)C-LUBT/H(2) INBT. Five Hundred mg of lactoseureide was ingested on the day before the test to induce an adequate enzyme activity in colonic bacteria. For the test, they received 500 mg of lactose[(13)C]ureide and 5 g inulin, dissolved in 400 mL of a standard enteral liquid nutrition orally. Breath samples were collected every 30 min for 8 h and analysed for H(2)[ p.p.m.] and (13)CO(2)-enrichment [delta (13)C]. For the (13)C-LUBT, the OCTT was defined as the interval with an increase of delta > 2.5SD above the running average of all previous points. The latter was defined as a rise of > 10ppm above baseline regarding the H(2)-INBT. RESULTS: Breath tests produced evaluable data in 27/29 patients [93%]. Median OCTTs were 315 min (range 210-450 min) for the (13)C-LUBT and 300 min (180-420 min) for the H(2)-INBT (P = 0.15). The (13)C-LU-OCTT correlated well with the H(2)-IN-OCTT (r = 0.72). Bland-Altman blot showed that the mean H(2)-IN-OCTTs were approximately 30 min shorter than predicted with the (13)C-LUBT. CONCLUSIONS: Inulin is a reliable and inexpensive substrate for a hydrogen-based assessment of the OCTT. In contrast to the (13)C-LUBT, the H(2)-INBT does not require patients to refrain from physical activity and may additionally increase its acceptance for clinical purposes. PMID- 17727673 TI - Liposomal cytarabine for treatment of myeloid central nervous system relapse in chronic myeloid leukaemia occurring during imatinib therapy. AB - BACKGROUND: Central nervous system (CNS) relapse in chronic myeloid leukaemia (CML) is rare and if recorded is usually found to occur in patients with lymphoblastic transformation. The BCR/ABL tyrosine kinase inhibitor imatinib is highly effective in patients with CML, but hardly crosses the blood-brain barrier. PATIENTS AND METHODS: We report on two CML patients who developed a myeloid CNS relapse during treatment with imatinib. One patient was in major cytogenetic response at the time of CNS relapse. In both cases, the myeloid origin of neoplastic cells in the cerebrospinal fluid (CSF) was demonstrable by immunophenotyping, and their leukaemic origin by detection of the BCR/ABL oncoprotein. No BCR/ABL kinase domain mutations were found. Both patients received intrathecal liposomal cytarabine (50 mg each cycle; 6 cycles). In one patient, additional CNS radiation was performed, whereas in the other, consecutive treatment with dasatinib (70 mg per os twice daily) was started. RESULTS: In response to therapy, the clinical symptoms resolved, and the leukaemic cells in the CSF disappeared in both cases. After three months of observation, both patients are in complete cytogenetic and major molecular response, without evidence for a systemic or a CNS relapse. CONCLUSIONS: 'Anatomic' resistance against imatinib in the CNS can lead to a myeloid CNS relapse. Liposomal cytarabine with or without radiation is effective as local therapy in these patients. For systemic treatment and prophylaxis, BCR/ABL kinase inhibitors crossing the blood-brain barrier such as dasatinib should be considered in patients with CNS relapse. PMID- 17727674 TI - Platelet function to estimate the bleeding risk in autoimmune thrombocytopenia. AB - BACKGROUND: Knowledge of platelet function may assist in patient care in chronic autoimmune thrombocytopenia (cAITP). MATERIALS AND METHODS: We evaluated the association of platelet function with haemorrhage in 41 patients, median age 41 years (range 14-82 years, 24 females) with chronic autoimmune thrombocytopenia (cAITP). Samples were investigated for platelet P-selectin, and adhesion and aggregate formation under high shear conditions. Data were compared to those from 28 healthy controls (median age 39 years, range 23-70 years, 17 females) and correlated with a bleeding score of 0 (no bleeding) to 3 (overt mucosal bleedings). RESULTS: P-selectin levels were higher in patients than in controls (P < 0.0004). Compared to controls, the patients' samples responded to high shear with decreased adhesion to the polystyrene surface (P < 0.0001), but formed aggregates of normal size. P-selectin expression was neither correlated with platelet counts, nor platelet adhesion, nor the bleeding score. Only the size of formed aggregates correlated with P-selectin (P = 0.01). Platelet counts (odds ratio 0.5, 95% confidence interval 0.22-0.88; P = 0.04) and adhesion (odds ratio 0.45, 95% confidence interval 0.17-0.87; P = 0.04) were independently inversely correlated with bleeding symptoms. CONCLUSION: Platelet adhesion correlates with bleeding symptoms, while the size of aggregates that are formed under high shear correlates with in vivo platelet activation. The determination of these parameters may assist in estimating an individual bleeding risk and thus a decision for treatment. PMID- 17727675 TI - How good are we at diagnosing polycystic ovary syndrome? PMID- 17727676 TI - Effect of the combination of the variants -75G/A APOA1 and Trp64Arg ADRB3 on the risk of type 2 diabetes (DM2). AB - OBJECTIVE: Numerous genes have been associated with the risk for type 2 diabetes mellitus (DM2). In an attempt to understand how specific variants of different genes interact and intervene in the molecular and physiological mechanisms of disorders such as diabetes or insulin resistance, the search for gene-gene interactions is constantly growing. We searched for a possible interaction between two polymorphisms (Trp64Arg of ADRB3 gene and -75G/A of APOA1gene) and the risk for DM2 in a population from southern Spain. DESIGN AND METHODS: A cross sectional study in southern Spain of 1020 people, aged 18-65 years. All persons underwent a clinical, anthropometrical and biochemical evaluation, including an oral glucose tolerance test (OGTT). Insulin resistance was measured by homeostasis model of assessment (HOMA). The polymorphisms -75G/A of APOA1 and Trp64Arg of ADRB3 were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and real-time PCR, respectively. RESULTS: The genotype frequencies of the -75G/A polymorphism of the APOA1 gene were 62.7% GG, 25.7% GA and 11.6% AA, whereas for the Trp64Arg polymorphism of the ADRB3 gene, they were 87.5% Trp/Trp, 11.7% Trp/Arg and 0.8% Arg/Arg. Subjects with both gene variants had a greater odds ratio (OR) of having DM2 [OR = 5.5; 95% confidence interval (CI) = 1.2-23.5] than persons with one or none of the variants, after adjusting for age, sex, body mass index (BMI) and homeostasis model assessment of insulin resistance (HOMA-IR). CONCLUSIONS: Joint association of allele -75A (APOA1) and allele Arg64 (ADRB3) increase the risk of DM2 in a population from southern Spain. PMID- 17727677 TI - A polymorphism in the resistin gene promoter and the risk of coronary artery disease in a Chinese population. AB - OBJECTIVE: Resistin, a novel adipocyte-derived peptide, has been linked to the pathogenesis of atherosclerosis. Recently, -420C>G, a variant located in the promoter region of the resistin gene (RETN) was identified. The aim of this study was to investigate the association between this RETN-420C>G polymorphism and the risk of coronary artery disease (CAD). DESIGN: A hospital-based case-control study. PATIENTS: A total of 225 CAD patients and 225 age- and sex-matched control subjects. MEASUREMENTS: Genotyping was performed by polymerase chain reaction (PCR) and restriction enzyme analysis to detect the presence of the RETN-420C>G polymorphism. RESULTS: The frequencies of RETN-420C>G genotypes in the CAD group were significantly different from those in the control group (P = 0.024). Subjects with the variant genotypes (CG and GG) had a 62% increased risk of CAD compared to CC carriers [adjusted odds ratio (OR) = 1.62, 95% confidence interval (CI) = 1.09-2.41, P = 0.016]. However, there were no significant differences between the genotypes with respect to weight, body mass index (BMI) and lipid profiles in CAD patients, and no significant association was found between the RETN-420C>G polymorphism and the severity of CAD. CONCLUSIONS: Our data suggest that the RETN-420C>G polymorphism might be associated with an increased risk of CAD in a Chinese population. PMID- 17727678 TI - Concentrations of the acute phase reactants high-sensitive C-reactive protein and YKL-40 and of interleukin-6 before and after treatment in patients with acromegaly and growth hormone deficiency. AB - BACKGROUND: Acromegaly is accompanied by increased cardiovascular mortality and a cluster of proatherogenic risk factors. In the general population, ischaemic heart disease (IHD) is associated with elevated levels of inflammatory markers. The acute phase reactant (APR) C-reactive protein (CRP) has been reported to be reduced in acromegaly and increase after treatment, suggesting that excess of GH/IGF-I could have anti-inflammatory effects. This is in accordance with results obtained in patients with growth hormone deficiency (GHD), where increased levels of CRP have been reported. OBJECTIVE: To investigate the hypothesis that the GH/IGF-I system is a suppressive regulator of inflammatory processes. SUBJECTS AND METHODS: Twenty-one acromegalic patients and 19 GH-deficient patients were studied. The two APRs CRP and YKL-40 and the proinflammatory cytokine interleukin 6 (IL-6) were measured before and after treatment and in healthy matched controls. RESULTS: In acromegalic patients, serum concentrations of high sensitive CRP (hsCRP) and YKL-40 were reduced compared to controls (P < 0.001) and increased (P < 0.001) after treatment, together with IL-6 (P = 0.021), to levels comparable with controls. Pretreatment serum YKL-40 and IL-6 showed a significant inverse correlation with IGF-I and GH. In GH-deficient patients, hsCRP and YKL-40 were elevated compared to controls (P = 0.001 and P = 0.048). During treatment, levels of both APRs showed a trend towards a decrease (P = 0.087 and P = 0.060), and after treatment, levels of YKL-40 no longer differed from that of controls. Serum IL-6 was not different from controls and did not change during GH treatment. CONCLUSION: The results point to the possibility of a relationship between GH disturbances and inflammatory processes. PMID- 17727679 TI - Nuclear translocation of ADAM-10 contributes to the pathogenesis and progression of human prostate cancer. AB - A disintegrin and metalloproteases (ADAM) are cell membrane-anchored proteins with potential implications for the metastasis of human cancer cells via cell adhesion and protease activities. In prostate cancer (PC), the ADAM-10 protein showed a nuclear localization whereas in benign prostate hypertrophy (BPH) it was predominantly bound to the cell membrane. We hypothesized that the pathogenesis and progression of PC are attributable to the nuclear translocation of ADAM-10. Immunoblotting revealed that after 5alpha-dihydrotestosterone treatment, a 60-kDa active form of ADAM-10 was increased in the nuclear fraction but decreased in the cell membrane and cytoplasmic fractions of human androgen-dependent PC cells. Immunocytochemistry revealed that after 5alpha-dihydrotestosterone treatment, the ADAM-10 protein was translocated from the cell membrane to the nucleus. Coimmunoprecipitation of androgen receptor and ADAM-10 was detected in the nuclear fraction but not in the cell membrane and cytoplasmic fractions. Immunohistochemical study of 64 PC and 20 BPH samples showed that the intensity of ADAM-10 staining was significantly higher in the nuclei of PC cells than in the nuclei of BPH cells (P < 0.0001). It was also significantly lower in the cell membrane of PC cells than in the cell membrane of BPH cells (P = 0.0017). Nuclear staining intensity was significantly correlated with the clinical T-factor (P = 0.004), the Gleason score (P < 0.0001) and preoperative prostate-specific antigen levels (P = 0.0061). ADAM-10 small interfering RNA transfectants showed a significant decrease in cell growth compared to the controls. Our results suggest that in human PC, the nuclear translocation of ADAM-10 coupled with the androgen receptor is involved in tumor growth and progression. PMID- 17727680 TI - Functional roles of Fli-1, a member of the Ets family of transcription factors, in human breast malignancy. AB - The Ets family of transcription factors is implicated in malignant transformation and tumor progression, including invasion, metastasis and neo-angiogenesis. In the present study, we found that the Fli-1 gene, a member of the Ets family, was highly expressed in several breast cancer cell lines (MDA-MB231, MDA-MB436, BT 549 and HCC1395). To investigate the functional roles of Fli-1 in breast cancer malignancy, we introduced an expression plasmid containing full-length Fli-1 cDNA into MCF7 breast cancer cells in which endogenous expression of Fli-1 was barely detectable.Overexpression of Fli-1 in MCF7 cells led to inhibition of apoptosis induced by serum depletion or ultraviolet irradiation, although it did not affect cell growth rate in liquid media, colony formation in soft agar or the in vitro invasion capacity of the cells. Expression of Fli-1 and antiapoptotic bcl-2 was coordinately upregulated by serum depletion in MCF7 cells, and the upregulation was inhibited by treatment of the cells with a c-Jun-NH(2)-terminal kinase specific inhibitor. Furthermore, expression of the bcl-2 gene and protein was enhanced in Fli-1-overexpressing MCF7 cells compared with mock-transfected cells. In addition, human bcl-2 promoter activity was transactivated by Fli-1. These results suggest that Fli-1 contributes to the malignancy of human breast cancer by inhibiting apoptosis through upregulated expression of the bcl-2 gene. PMID- 17727681 TI - CCAAT/enhancer binding protein-beta promotes the survival of intravascular rat pancreatic tumor cells via antiapoptotic effects. AB - A transcriptional factor, CCAAT/enhancer binding protein-beta (C/EBP-beta), regulates a variety of cell functions in normal and neoplastic cells. Although the involvement of C/EBP-beta in metastasis has been demonstrated clinicopathologically in several types of human cancer, the mechanism by which it functions during the multistep process of metastasis remains largely unknown. We investigated the role of C/EBP-beta in the intravascular step of hematogenous metastasis in a rat pancreatic tumor cell line, AR42J-B13, as this step profoundly affects metastatic efficiency. C/EBP-beta-transfected AR42J-B13 (betaB13) cells acquired considerable resistance against serum toxicity, which was primarily mediated by apoptosis in vitro. Upregulated expression of Bcl-2 and Bcl-xL was seen in betaB13 cells. Enhanced early survival of intraportally injected betaB13 cells in the BALB/c nu/nu male mice liver, detected by the mRNA of a vector-specific gene, was observed. Nick-end labeling analysis of the tumor injected liver revealed significantly lower rates of apoptosis among intravascular betaB13 tumor cells than among empty vector-transfected AR42J-B13 (mB13) cells. Finally, intrasplenically injected betaB13 cells established a larger number of colonies in the liver than did the mB13 cells. These findings suggest that C/EBP-beta may enhance hematogenous metastasis and its antiapoptotic effects may promote the survival of intravascular tumor cells. PMID- 17727682 TI - Soy-derived isoflavones inhibit the growth of adult T-cell leukemia cells in vitro and in vivo. AB - Adult T-cell leukemia occurs in human T-lymphotropic virus type I-infected individuals and is endemic to the south-western area of Kyushu in Japan. In this communication, we examined the effect of soy isoflavones on the growth of adult T cell leukemia cells in vitro and in vivo. In the in vitro study, daidzein and genistein but not glycitein significantly inhibited the proliferation of ED-40515 and Hut102 cells in a dose-dependent manner. Among the isoflavones studied, genistein had the highest growth-inhibitory effect; however, genistein did not exert an apparent growth-inhibitory effect on Jurkat and Molt-4 cells, which were non-adult T-cell leukemia cells. Genistein prevented the G(1)/S or G(2)/M transition at 3 and 10 or 30 microM, respectively. Genistein upregulated p21 protein expression together with p53 accumulation. In addition, treatment with 30 microM genistein strongly induced phosphorylation of checkpoint kinase (CHK) 2 and p53 at serines 15, 20 and 37. Caffeine, an inhibitor of ataxia-telangiectasia mutated protein kinase, alleviated the genistein-induced p53 and CHK2 phosphorylation, suggesting the involvement of DNA damage at 30 microM. However, marked phosphorylation of CHK2 and p53 could not be detected at 3 and 10 microM genistein. These data indicate that genistein has biphasic growth-inhibitory properties. The in vivo studies demonstrated that soy-derived isoflavones significantly inhibit ED-40515 cell growth and infiltration into various organs in non-obese diabetic severe combined-immunodeficiency common gamma-chain knockout mice. Taken together, it is evident that soy isoflavones might serve as a promising compound for the treatment of adult T-cell leukemia. PMID- 17727684 TI - Functional implications of tetraspanin proteins in cancer biology. AB - Human tetraspanin proteins are a group of 33 highly hydrophobic membrane proteins that can form complexes in cholesterol-rich microdomains, distinct from lipid rafts, on the cell surface in a dynamic and reversible way. These complexes are composed of a core of several tetraspanin proteins that organize other membrane proteins such as integrins, human leukocyte antigen (HLA) antigens and some growth factor receptors. Although most tetraspanin proteins have been studied individually, tetraspanin proteins and their complexes can have effects on cellular adhesion and motility, interactions with stroma or affect signaling by growth factors, and for most of them no ligand has been identified. Functionally these proteins have been mostly studied in cells of lymphoid lineage, but they are present in all cell types. Data is also available for some tumors, where some tetraspanins have been identified as metastasis suppressors, but their significance is still not clear. Some of their implications in tumor biology and the areas that deserve further study are outlined. PMID- 17727683 TI - Discrimination of metabolic profiles of pancreatic cancer from chronic pancreatitis by high-resolution magic angle spinning 1H nuclear magnetic resonance and principal components analysis. AB - The metabolic profiles of Sprague-Dawley rat pancreases were investigated by high resolution magic angle spinning proton magnetic resonance spectroscopy ((1)H NMR) combined with principal components analysis (PCA) to discriminate pancreatic cancer from chronic pancreatitis. Intact pancreatic tissue samples were obtained from Sprague-Dawley rats with histologically proven pancreatic cancer (n = 5), chronic pancreatitis (n = 5), and two matched controls (n = 5 per group). Two (1)H NMR experiments, single-pulse and Carr-Purcell-Meiboom-Gill, were carried out separately. Increases in phosphocholine and glycerophosphocholine levels and decreases in leucine, isoleucine, valine, lactate and alanine levels were observed in chronic pancreatitis, whereas the opposite trends were observed in pancreatic cancer. Increasing taurine and decreasing betaine were found both in chronic pancreatitis and in pancreatic cancer. Additionally, the lipid content in pancreatic cancer was higher than that in chronic pancreatitis. PCA was carried out for the single-pulse and Carr-Purcell-Meiboom-Gill (1)H NMR spectra, respectively, to visualize separation among the samples and to extract characteristic metabolites of pancreatic cancer and chronic pancreatitis. Decreased phosphocholine and glycerophosphocholine were suggested as unique metabolite indicators of pancreatic cancer. Furthermore, even with the disturbance of various quantities of lipid contents pancreatic cancer and chronic pancreatitis could be differentiated well by the combination of high-resolution magic angle spinning (1)H NMR and PCA. Thus this combination was demonstrated to have the potential to improve magnetic resonance spectroscopy for positive early diagnosis of pancreatic cancer in clinical settings. PMID- 17727685 TI - Time-to-positivity in patients with Escherichia coli bacteraemia. AB - The time from the start of incubation to a positive reading of blood cultures (time-to-positivity; TTP) is related to the concentration of bacteria in blood. Information concerning the correlation of TTP with clinical parameters, and its usefulness as a prognostic factor in patients with Escherichia coli bacteraemia, is limited. To investigate the relationship of TTP to clinical parameters, 459 cases of monomicrobial E. coli bloodstream infections from a single institution between 1997 and 2005 were reviewed. All cases involved patients who were not undergoing antibiotic treatment at the time of blood sampling. The in-hospital mortality rate was 6.3%. Median TTP was significantly shorter for patients who died than for those who survived (9.7 h, inter-quartile range 7.85-11.05 h vs. 11.2 h, inter-quartile range 10.1-11.4 h; p <0.001). Patients with TTP in the lowest quartile were more likely to be female, to have a non-urinary tract or an unknown origin of bacteraemia, to have severe sepsis or shock, and to subsequently die. In a multivariable Cox regression model, the hazard ratio for death from any cause for patients with a short TTP was 3.13 (95% CI 1.28-7.64; p 0.01). TTP in patients with E. coli bacteraemia provides prognostic information beyond that provided by the presence of haematological illness, a Charlson score > or =3, a non-urinary tract origin of bacteraemia, and the presence of severe sepsis or shock. PMID- 17727686 TI - The significance of the number of submitted samples and patient-related factors for faecal bacterial diagnostics. AB - The sensitivity of bacteriological testing of faecal samples from patients with diarrhoea has not been properly determined. The present study analysed the association between the results of stool sample examinations and the number of samples examined per patient and other patient-related factors. Data concerning faecal specimens referred for culture for enteric bacterial pathogens (Campylobacter, Salmonella, Shigella and Yersinia) to the central microbiological laboratory in Denmark between 1995 and 2003 were analysed. In total, 620 000 samples were sorted into 277 000 sample-series, i.e., samples submitted from the same individual on the same day. Data were analysed by multivariate logistic regression, with the outcome being a positive sample-series, i.e., one or more positive samples per series. Overall, 11.9% of the sample-series were positive. For adults (aged > or =18 years), the OR for a positive diagnosis was 1.20 (95% CI 1.18-1.21) for each additional sample. Positive diagnoses were also more likely during summer, if the patient was male, or if the patient was neither very young nor very old. The added diagnostic effect of additional samples was more pronounced for the group of patients with persistent (>2 weeks) diarrhoea. Overall, the probability of finding common pathogenic bacteria in faecal samples was found to vary according to the number of samples, the season and the patient's age and gender. Analysis of more than one sample improves the sensitivity of faecal culture by at least 20% for each additional sample. PMID- 17727687 TI - Differences in peripheral blood lymphocyte phenotypes between Helicobacter pylori positive children and adults with duodenal ulcer. AB - The immunological mechanisms involved in the development of duodenal ulcer, especially in childhood, are unclear. Helicobacter pylori-positive children and adults, with and without duodenal ulcer, were therefore compared with respect to CD4(+) T-cells, and CD8(+) T-cells, B-cells and B1a-cells, as well as cell activation (CD4(+)/HLA-DR(+) and CD8(+)/HLA-DR(+)) and co-stimulatory (CD4(+)/CD28(+) and CD8(+)/CD28(+)) markers, in peripheral blood. Children with and without duodenal ulcer differed significantly. In particular, there was a phenotypic change in CD8(+) T-cells from children with ulcer that involved a 200% increase in the number of CD8(+)/HLA-DR(+) cells/mm(3) and a decrease of 34.2% in the number of CD8(+)/CD28(+) cells/mm(3). This phenotype of chronically activated memory CD8(+) T-cells, which has also been observed in patients with AIDS and tuberculosis, is associated with disease severity and progression. A lower frequency of B1a-cells was also observed in the group of children with ulcer. Conversely, no difference between infected adults with and without ulcer was observed, but the percentage of CD4(+)/HLA-DR(+) cells was lower in adults with ulcer, suggesting that a down-regulated immune response may play a role in the development of duodenal ulcer in adults. Gastric inflammation correlated positively with CD4(+) and chronically activated CD4(+) T-cells in children and adults without duodenal ulcer, respectively. These results suggest that there are differences in the immunophenotyping profile between H. pylori-positive children and adults with duodenal ulcer, indicating the possibility of distinct immune mechanisms in the development of the disease according to age. PMID- 17727688 TI - National registry diagnoses agree with medical records on hospitalized asthmatic children. AB - AIM: The present study was performed to explore the validity of discharge diagnoses on asthma in the Danish National Patient Registry compared with medical records. METHODS: A review of medical records on all acute hospital admissions of 6-14-year-old children in 10 Danish hospitals between July and December 2002 was conducted. The personal registration number and dates on admissions due to asthma were sent to the Danish National Patient Registry for information on discharge diagnoses, and admission and discharge dates. Agreement between medical records and the Danish National Patient Registry was sought by sensitivity, specificity, and the positive and negative predictive value. RESULTS: Medical records of 3550 children aged 6-14 years were reviewed. A total of 300 admissions were due to asthma, 271 of which were also registered with an asthma diagnosis unit in the Danish National Patient Registry. Collection of data in the Danish National Patient Registry showed a surplus of 49 admissions due to asthma compared to hospital record data. The sensitivity of an asthma diagnosis in the registry then was 0.90, specificity 0.99, positive predictive value 0.85 and negative predictive value 0.99. CONCLUSIONS: Data on paediatric asthma diagnoses in the Danish National Patient Registry are valid and may serve as useful tools in research. PMID- 17727689 TI - Immunological patterns in young children with Down syndrome: is there a temporal trend? AB - Down syndrome is associated with an increased susceptibility to infections due to a deficiency of both specific and nonspecific immunity. AIM: The aim of the study was to analyze the temporal trends, if any, of some variables related to the immunological status of children affected by Down syndrome. METHODS: Heparinized blood samples were obtained by venipuncture in 30 children with Down syndrome, who were regularly followed in our department and analyzed for hematologic values, lymphocyte subpopulations, immunoglobulin dosage and zinc level. Results were compared with those of the normal population. RESULTS: In the first 5 years of life, we observed a progressive decrease in the medium values of lymphocytes, CD4(+) and plasma zinc levels, and an increase in CD8(+), immunoglobulin A, immunoglobulin G, immunoglobulin M and natural killer, but generally without exceeding the interval of normality. CONCLUSIONS: In Down syndrome children, the immune cellular status is similar to the normal population as far as white blood cell, lymphocyte, CD4(+), CD8(+), natural killer and immunoglobulins are concerned. Plasma level of zinc is normal from birth until 5 years but with a temporal trend of progressive reduction. This observation supports the hypothesis that a pharmacological supplementation may be necessary in Down syndrome children only after 5 years of age. PMID- 17727690 TI - Nurses promote openness regarding the genetic origins after gamete donation. AB - AIM: To study attitudes and knowledge concerning different aspects of sperm and oocyte donation among paediatric nurses at child health care centres (CHCs) in Sweden. METHOD: A study-specific questionnaire, to be completed anonymously, was sent to 188 nurses, 141 of whom (75%) responded. RESULTS: The majority of the respondents (62%) stated that they had no professional experience of families created with the help of a donor. A majority (53%) stated that they had good knowledge of the procedure followed in sperm donation, whereas 43% stated that they had good knowledge of the procedure of oocyte donation. More than 80% agreed that the parents should be honest with their child with regard to the child's genetic origin. Among the respondents who were in favour of disclosure, the preferred age for informing the child varied between 0 to 19 years (mean 7.2, SD 5.7). CONCLUSION: We conclude that the nurses working in CHCs need guidance and information about gamete donation in order to be able to support parents in the disclosure of information to their children and also how to inform or withhold information to significant others in their surrounding milieu. PMID- 17727691 TI - Noninvasive peripheral perfusion index as a possible tool for screening for critical left heart obstruction. AB - AIM: Peripheral perfusion index (PPI) has been suggested as a possible method to detect illness causing circulatory embarrassment. We aimed to establish the normal range of this index in healthy newborns, and compare it with newborns with duct-dependent systemic circulation. DESIGN: We conducted a case-control study. SETTING: Our study population comprised 10,000 prospectively recruited newborns from Vastra Gotaland, Sweden. PATIENTS: A total of 10,000 normal newborns and 9 infants with duct-dependent systemic circulation (left heart obstructive disease [LHOD] group) participated in the study. METHODS: We conducted single pre- and postductal measurements of PPI with a new generation pulse oximeter (Masimo Radical SET) before discharge from hospital. RESULTS: PPI values between 1 and 120 h of age show an asymmetrical, non-normal distribution with median PPI value of 1.70 and interquartile range of 1.18-2.50. The 5th percentile = 0.70 and 95th percentile = 4.50. All infants in the LHOD group had either pre- or postductal PPI below the interquartile range, and 5 of 9 (56%) were below the 5th percentile cut-off of 0.70 (p < 0.0001, Fisher's exact test). A PPI value <0.70 gave an odds ratio for LHOD of 23.75 (95% CI 6.36-88.74). CONCLUSION: PPI values lower than 0.70 may indicate illness and a value <0.50 (1st percentile) indicates definite underperfusion. PPI values might be a useful additional tool for early detection of LHOD. PMID- 17727692 TI - Mistaken identity of skin cleansing solution leading to extensive chemical burns in an extremely preterm infant. AB - Chemical burns in extremely preterm infants have major implications in terms of morbidity and risk management. We report a case of extensive chemical burn in an extremely low birth weight (ELBW) infant caused by clear, colourless solution of 0.5% chlorhexidine in 70% alcohol mistaken for normal saline for skin cleansing during umbilical catheter insertion. This case reflects the on going problem faced by many neonatal intensive care units of similar coloured solutions with similar packages, but with varying degrees of toxic effects. CONCLUSION: The case highlights the importance of having a clear policy for skin cleansing in every neonatal unit and measures to avoid errors by vigilant checking of all medications including topical solutions. PMID- 17727693 TI - Variance in multiplex suspension array assays: intraplex method improves reliability. AB - BACKGROUND: Flow cytometry based suspended microarray assays are susceptible to many sources of variance; multi-well replication and inter-instrument reproducibility is uncertain. METHOD AND RESULTS: An "intraplex" method was developed in order to minimize differences in sample readings between instruments. A full intraplex assay consists of a set m of microparticle set classifications assaying for the same analyte, with each of the m classifier sets having different sensitivity to analyte, and n classifier sets replicating each of the m levels of sensitivity, where m > 1 (generally m > 4 would be used). CONCLUSION: The intraplex method can compensate adequately for the sources of variance that have been identified in suspended microarray assays. It requires no changes to current equipment in use, and is a superior method of constructing precision assays. Additionally, Luminex users may want to consider the evidence that shows that despite calibration to the same standard, two instruments may not give similar results for all concentrations of analytes. PMID- 17727694 TI - Gene conversion limits divergence of mammalian TLR1 and TLR6. AB - BACKGROUND: Toll-like receptors (TLR) recognize pathogen-associated molecular patterns and are important mediators of the innate immune system. TLR1 and TLR6 are paralogs and located in tandem on the same chromosome in mammals. They form heterodimers with TLR2 and bind lipopeptide components of gram-positive and gram negative bacterial cell walls. To identify conserved stretches in TLR1 and TLR6, that may be important for their function, we compared their protein sequences in nine mammalian species(Homo sapiens, Pan troglodytes, Macaca mulatta, Mus musculus, Rattus norvegicus; Erinaceus europaeus, Bos Taurus, Sus scrofa and Canis familiaris). RESULTS: The N-terminal sequences of the orthologous proteins showed greater similarity than corresponding paralog sequences. However, we identified a region of 300 amino acids towards the C-terminus of TLR1 and TLR6, where paralogs had a greater degree of sequence identity than orthologs. Preservation of DNA sequence identity of paralogs in this region was observed in all nine mammalian species investigated, and is due to independent gene conversion events. The regions having undergone gene conversion in each species are almost identical and encode the leucine-rich repeat motifs 16 to 19, the C terminal cap motif, the transmembrane domain and most of the intracellular Toll/interleukin-1 receptor (TIR) domain. CONCLUSION: Our results show that, for a specific conserved region, divergence of TLR1 and TLR6 is limited by gene conversion, most likely because of the need for co-evolution with multiple intracellular and extracellular binding partners. Thus, gene conversion provides a mechanism for limiting the divergence of functional regions of protein paralogs, while allowing other domains to evolve diversified functions. PMID- 17727695 TI - Studying the Hurdles of Insulin Prescription (SHIP): development, scoring and initial validation of a new self-administered questionnaire. AB - BACKGROUND: Although insulin therapy is well-accepted by symptomatic diabetic patients, it is still often delayed in less severe patients, in whom injectable insulin remains under-used. A better understanding of patients' perception of insulin would eventually help physicians to adopt the most appropriate dialogue when having to motivate patients to initiate or to intensify insulin injection. METHODS: The 'Studying the Hurdles of Insulin Prescription' (SHIP) questionnaire was developed based on a list of concepts derived from three diabetic patients' focus groups, and was included into two cross-sectional studies with similar design: SHIP Oral study and SHIP Premix study. Diabetic patients treated with oral hypoglycaemic agents (OHA; n = 1,494) and patients already treated with insulin (n = 1,150) completed the questionnaire at baseline, 6- and 12 months. Psychometric properties were assessed: 1) structure analysis by Principal Component Analysis (PCA) with Varimax rotation, 2) internal consistency reliability (Cronbach's alpha), and 3) concurrent validity (Spearman correlation coefficients with the Fear of Self-Injecting (FSI) score of the Diabetes Fear of Injecting and Self-testing Questionnaire. Reluctance/motivation towards insulin was assessed. Scores' ability to predict patients' insulin injection reluctance/motivation and initiation/intensification was evaluated with the Area Under the Receiver Operating Characteristic (ROC) Curve (AUC). RESULTS: PCA analysis confirmed the structure of the 14 items grouped into 3 dimensions: 'acceptance and motivation', 'fear and constraints', and 'restraints and barriers' towards insulin injection. Internal consistency reliability was excellent (Cronbach's alpha > 0.70); concurrent validity was good. The three scores were significantly predictive of patients' reluctance/motivation towards insulin injection initiation, as they were of patients' actual switch, except for the 'restraints and barriers' dimension. 'Acceptance and motivation' and 'fears and constraints' dimensions were also significantly predictive of patients' reluctance/motivation towards insulin intensification. By the end of the 12-month study, 179 of the initially OHA-treated patients had started insulin injections; 186 of the patients already treated with insulin had increased their injections. CONCLUSION: The SHIP questionnaire provides reliable and valid assessment of diabetic patients' attitude towards insulin and injections. The predictive power of scores for patients' reluctance/motivation and actual treatment decisions demonstrates encouraging potential for further application in clinical practice. PMID- 17727696 TI - Mast cells and eosinophils in invasive breast carcinoma. AB - BACKGROUND: Inflammatory cells in the tumour stroma has gained increasing interest recently. Thus, we aimed to study the frequency and prognostic impact of stromal mast cells and tumour infiltrating eosinophils in invasive breast carcinomas. METHODS: Tissue microarrays containing 234 cases of invasive breast cancer were prepared and analysed for the presence of stromal mast cells and eosinophils. Tumour infiltrating eosinophils were counted on hematoxylin-eosin slides. Immunostaining for tryptase was done and the total number of mast cells were counted and correlated to the proliferation marker Ki 67, positivity for estrogen and progesterone receptors, clinical parameters and clinical outcome. RESULTS: Stromal mast cells were found to correlate to low grade tumours and estrogen receptor positivity. There was a total lack of eosinophils in breast cancer tumours. CONCLUSION: A high number of mast cells in the tumours correlated to low-grade tumours and estrogen receptor positivity. Eosinophils are not tumour infiltrating in breast cancers. PMID- 17727697 TI - Age-specific prevalence of the metabolic syndrome defined by the International Diabetes Federation and the National Cholesterol Education Program: the Norwegian HUNT 2 study. AB - BACKGROUND: The 2005 International Diabetes Federation (IDF) definition of the metabolic syndrome was designed to be useful worldwide, but to date few prevalence studies have used that definition in European populations. We estimated the age- and sex-stratified prevalence of IDF-defined metabolic syndrome in a county of Norway and compared it with the prevalence estimated using the revised National Cholesterol Education Program-Adult Treatment Panel III definition (2005 ATP III). METHODS: Cross-sectional analysis of 10,206 participants aged 20-89 years in the Nord-Trondelag Health Study 1995-97 (HUNT 2). RESULTS: Prevalence of IDF-defined metabolic syndrome was 29.6% (95% CI: 28.8 to 30.5), compared to 25.9% (95% CI: 25.0 to 26.7) using the 2005 ATP III criteria. The prevalence of IDF-defined metabolic syndrome increased from 11.0% in the 20-29 years age group to 47.2% in the 80-89 years group in men, and from 9.2% to 64.4% for women in the corresponding age groups. Among men and women aged >or=60 years, the IDF criteria classified 56.7% and 75.0%, respectively, as having central obesity, and 89.3% and 90.9%, respectively, as being hypertensive. CONCLUSION: According to both definitions, the prevalence of the metabolic syndrome increased strongly with age. The IDF and the American Heart Association/National Heart, Lung, and Blood Institute guidelines for clinical management of metabolic syndrome would classify a high proportion of elderly Norwegians as in need of overall risk assessment for cardiovascular disease. PMID- 17727698 TI - Mitotic regulation by NIMA-related kinases. AB - The NIMA-related kinases represent a family of serine/threonine kinases implicated in cell cycle control. The founding member of this family, the NIMA kinase of Aspergillus nidulans, as well as the fission yeast homologue Fin1, contribute to multiple aspects of mitotic progression including the timing of mitotic entry, chromatin condensation, spindle organization and cytokinesis. Mammals contain a large family of eleven NIMA-related kinases, named Nek1 to Nek11. Of these, there is now substantial evidence that Nek2, Nek6, Nek7 and Nek9 also regulate mitotic events. At least three of these kinases, as well as NIMA and Fin1, have been localized to the microtubule organizing centre of their respective species, namely the centrosome or spindle pole body. Here, they have important functions in microtubule organization and mitotic spindle assembly. Other Nek kinases have been proposed to play microtubule-dependent roles in non dividing cells, most notably in regulating the axonemal microtubules of cilia and flagella. In this review, we discuss the evidence that NIMA-related kinases make a significant contribution to the orchestration of mitotic progression and thereby protect cells from chromosome instability. Furthermore, we highlight their potential as novel chemotherapeutic targets. PMID- 17727699 TI - The mitochondrial DNA control region shows genetically correlated levels of heteroplasmy in leukocytes of centenarians and their offspring. AB - BACKGROUND: Studies on heteroplasmy occurring in the mitochondrial DNA (mtDNA) control region (CR) in leukocytes of centenarians and younger subjects have shown that the C150T somatic transition is over-represented in centenarians. However, whether the occurrence/accumulation of heteroplasmy is a phenotypic consequence of extreme ageing or a genetically controlled event that may favor longevity is a question that deserves further attention. To clarify this point, we set up a Denaturing High Performance Liquid Chromatography (DHPLC) protocol to quantify mtDNA CR heteroplasmy. We then analyzed heteroplasmy in leukocytes of centenarians (100 subjects), their offspring and nieces/nephews (200 subjects, age-range 65-80 years, median age 70 years), and in leukocytes of 114 control subjects sex- and age-matched with the relatives of centenarians. RESULTS: The centenarians and their descendants, despite the different ages, showed similar levels of heteroplasmy which were significantly higher than levels in controls. In addition we found that heteroplasmy levels were significantly correlated in parent-offspring pairs (r = 0.263; p = 0.009), but were independent of mtDNA inherited variability (haplogroup and sequence analyses). CONCLUSION: Our findings suggest that the high degree of heteroplasmy observed in centenarians is genetically controlled, and that such genetic control is independent of mtDNA variability and likely due to the nuclear genome. PMID- 17727700 TI - How human practices have affected vector-borne diseases in the past: a study of malaria transmission in Alpine valleys. AB - BACKGROUND: Malaria was endemic in the Rhone-Alpes area of eastern France in the 19th century and life expectancy was particularly shortened in Alpine valleys. This study was designed to determine how the disease affected people in the area and to identify the factors influencing malaria transmission. METHODS: Demographic data of the 19th century were collected from death registers of eight villages of the flood-plain of the river Isere. Correlations were performed between these demographic data and reconstructed meteorological data. Archive documents from medical practitioners gave information on symptoms of ill people. Engineer reports provided information on the hydraulic project developments in the Isere valley. RESULTS: Description of fevers was highly suggestive of endemic malaria transmission in the parishes neighbouring the river Isere. The current status of anopheline mosquitoes in the area supports this hypothesis. Mean temperature and precipitation were poorly correlated with demographic data, whereas the chronology of hydrological events correlated with fluctuations in death rates in the parishes. CONCLUSION: Nowadays, most of the river development projects involve the creation of wet areas, enabling controlled flooding events. Flood-flow risk and the re-emergence of vector-borne diseases would probably be influenced by the climate change. The message is not to forget that human disturbance of any functioning hydrosystem has often been linked to malaria transmission in the past. PMID- 17727701 TI - The D9N, N291S and S447X variants in the lipoprotein lipase (LPL) gene are not associated with Type III hyperlipidemia. AB - BACKGROUND: Type III hyperlipidemia (Type III HLP) is associated with homozygosity for the epsilon2 allele of the APOE gene. However only about 10% of epsilon2 homozygotes develop Type III HLP and it is assumed that additional genetic and/or environmental factors are required for its development. Common variants in the LPL gene have been proposed as likely genetic co-factors. METHODS: The frequency of the LPL SNPs D9N, N291S and S447X in 100 patients with hyperlipidemia and APOE2/2 genotype has been determined and compared to that in healthy blood donors and patients with hyperlipidemia. RESULTS: There were no statistically significant difference in the frequencies of the variants between APOE2/2 patients and controls. CONCLUSION: It is unlikely that the D9N, N291S or S447X variants in the LPL gene play an important role in the development of Type III HLP. PMID- 17727703 TI - Spectrum of disease-causing mutations in protein secondary structures. AB - BACKGROUND: Most genetic disorders are linked to missense mutations as even minor changes in the size or properties of an amino acid can alter or prevent the function of the protein. Further, the effect of a mutation is also dependent on the sequence and structure context of the alteration. RESULTS: We investigated the spectrum of disease-causing missense mutations in secondary structure elements in proteins with numerous known mutations and for which an experimentally defined three-dimensional structure is available. We obtained a comprehensive map of the differences in mutation frequencies, location and contact energies, and the changes in residue volume and charge - both in the mutated (original) amino acids and in the mutant amino acids in the different secondary structure types. We collected information for 44 different proteins involved in a large number of diseases. The studied proteins contained a total of 2413 mutations of which 1935 (80%) appeared in secondary structures. Differences in mutation patterns between secondary structures and whole proteins were generally not statistically significant whereas within the secondary structural elements numerous highly significant features were observed. CONCLUSION: Numerous trends in mutated and mutant amino acids are apparent. Among the original residues, arginine clearly has the highest relative mutability. The overall relative mutability among mutant residues is highest for cysteine and tryptophan. The mutability values are higher for mutated residues than for mutant residues. Arginine and glycine are among the most mutated residues in all secondary structures whereas the other amino acids have large variations in mutability between structure types. Statistical analysis was used to reveal trends in different secondary structural elements, residue types as well as for the charge and volume changes. PMID- 17727702 TI - Design and evaluation of Actichip, a thematic microarray for the study of the actin cytoskeleton. AB - BACKGROUND: The actin cytoskeleton plays a crucial role in supporting and regulating numerous cellular processes. Mutations or alterations in the expression levels affecting the actin cytoskeleton system or related regulatory mechanisms are often associated with complex diseases such as cancer. Understanding how qualitative or quantitative changes in expression of the set of actin cytoskeleton genes are integrated to control actin dynamics and organisation is currently a challenge and should provide insights in identifying potential targets for drug discovery. Here we report the development of a dedicated microarray, the Actichip, containing 60-mer oligonucleotide probes for 327 genes selected for transcriptome analysis of the human actin cytoskeleton. RESULTS: Genomic data and sequence analysis features were retrieved from GenBank and stored in an integrative database called Actinome. From these data, probes were designed using a home-made program (CADO4MI) allowing sequence refinement and improved probe specificity by combining the complementary information recovered from the UniGene and RefSeq databases. Actichip performance was analysed by hybridisation with RNAs extracted from epithelial MCF-7 cells and human skeletal muscle. Using thoroughly standardised procedures, we obtained microarray images with excellent quality resulting in high data reproducibility. Actichip displayed a large dynamic range extending over three logs with a limit of sensitivity between one and ten copies of transcript per cell. The array allowed accurate detection of small changes in gene expression and reliable classification of samples based on the expression profiles of tissue-specific genes. When compared to two other oligonucleotide microarray platforms, Actichip showed similar sensitivity and concordant expression ratios. Moreover, Actichip was able to discriminate the highly similar actin isoforms whereas the two other platforms did not. CONCLUSION: Our data demonstrate that Actichip is a powerful alternative to commercial high density microarrays for cytoskeleton gene profiling in normal or pathological samples. Actichip is available upon request. PMID- 17727704 TI - Disruption and pseudoautosomal localization of the major histocompatibility complex in monotremes. AB - BACKGROUND: The monotremes, represented by the duck-billed platypus and the echidnas, are the most divergent species within mammals, featuring a flamboyant mix of reptilian, mammalian and specialized characteristics. To understand the evolution of the mammalian major histocompatibility complex (MHC), the analysis of the monotreme genome is vital. RESULTS: We characterized several MHC containing bacterial artificial chromosome clones from platypus (Ornithorhynchus anatinus) and the short-beaked echidna (Tachyglossus aculeatus) and mapped them onto chromosomes. We discovered that the MHC of monotremes is not contiguous and locates within pseudoautosomal regions of two pairs of their sex chromosomes. The analysis revealed an MHC core region with class I and class II genes on platypus and echidna X3/Y3. Echidna X4/Y4 and platypus Y4/X5 showed synteny to the human distal class III region and beyond. We discovered an intron-containing class I pseudogene on platypus Y4/X5 at a genomic location equivalent to the human HLA B,C region, suggesting ancestral synteny of the monotreme MHC. Analysis of male meioses from platypus and echidna showed that MHC chromosomes occupy different positions in the meiotic chains of either species. CONCLUSION: Molecular and cytogenetic analyses reveal new insights into the evolution of the mammalian MHC and the multiple sex chromosome system of monotremes. In addition, our data establish the first homology link between chicken microchromosomes and the smallest chromosomes in the monotreme karyotype. Our results further suggest that segments of the monotreme MHC that now reside on separate chromosomes must once have been syntenic and that the complex sex chromosome system of monotremes is dynamic and still evolving. PMID- 17727705 TI - Expression patterns of semaphorin7A and plexinC1 during rat neural development suggest roles in axon guidance and neuronal migration. AB - BACKGROUND: Although originally identified as embryonic axon guidance cues, semaphorins are now known to regulate multiple, distinct, processes crucial for neuronal network formation including axon growth and branching, dendritic morphology, and neuronal migration. Semaphorin7A (Sema7A), the only glycosylphosphatidylinositol-anchored semaphorin, promotes axon growth in vitro and is required for the proper growth of the mouse lateral olfactory tract in vivo. Sema7A has been postulated to signal through two unrelated receptors, an RGD-dependent alpha1beta1-integrin and a member of the plexin family, plexinC1. beta1-integrins underlie Sema7A-mediated axon growth and Sema7A function in the immune system. Sema7A-plexinC1 interactions have also been implicated in immune system function, but the neuronal role of this ligand-receptor pair remains to be explored. To gain further insight into the function(s) of Sema7A and plexinC1 during neural development, we present here a detailed analysis of Sema7A and plexinC1 expression in the developing rat nervous system. RESULTS: In situ hybridization revealed select expression of Sema7A and plexinC1 in multiple neuronal systems including: the olfactory system, the hypothalamo-hypophysial system, the hippocampus, the meso-diencephalic dopamine system, and the spinal cord. Within these systems, Sema7A and plexinC1 are often expressed in specific neuronal subsets. In general, Sema7A transcript levels increase significantly towards adulthood, whereas plexinC1 expression decreases as development proceeds.PlexinC1, but not Sema7A, is strongly expressed by distinct populations of migrating neurons. In addition to neuronal expression, Sema7A and plexinC1 transcripts were detected in oligodendrocytes and ependymal cells, respectively. CONCLUSION: Sema7A and plexinC1 expression patterns are consistent with these proteins serving both cooperative and separate functions during neural development. The prominent expression of plexinC1 in several distinct populations of migrating neurons suggests a novel role for this plexin family member in neuronal migration. PMID- 17727707 TI - Non-coding antisense transcription detected by conventional and single-stranded cDNA microarray. AB - BACKGROUND: Recent studies revealed that many mammalian protein-coding genes also transcribe their complementary strands. This phenomenon raises questions regarding the validity of data obtained from double-stranded cDNA microarrays since hybridization to both strands may occur. Here, we wanted to analyze experimentally the incidence of antisense transcription in human cells and to estimate their influence on protein coding expression patterns obtained by double stranded microarrays. Therefore, we profiled transcription of sense and antisense independently by using strand-specific cDNA microarrays. RESULTS: Up to 88% of expressed protein coding loci displayed concurrent expression from the complementary strand. Antisense transcription is cell specific and showed a strong tendency to be positively correlated to the expression of the sense counterparts. Even if their expression is wide-spread, detected antisense signals seem to have a limited distorting effect on sense profiles obtained with double stranded probes. CONCLUSION: Antisense transcription in humans can be far more common than previously estimated. However, it has limited influence on expression profiles obtained with conventional cDNA probes. This can be explained by a biological phenomena and a bias of the technique: a) a co-ordinate sense and antisense expression variation and b) a bias for sense-hybridization to occur with more efficiency, presumably due to variable exonic overlap between antisense transcripts. PMID- 17727706 TI - Distribution patterns of small-molecule ligands in the protein universe and implications for origin of life and drug discovery. AB - BACKGROUND: Extant life depends greatly on the binding of small molecules (such as ligands) with macromolecules (such as proteins), and one ligand can bind multiple proteins. However, little is known about the global patterns of ligand protein mapping. RESULTS: By examining 2,186 well-defined small-molecule ligands and thousands of protein domains derived from a database of druggable binding sites, we show that a few ligands bind tens of protein domains or folds, whereas most ligands bind only one, which indicates that ligand-protein mapping follows a power law. Through assigning the protein-binding orders (early or late) for bio ligands, we demonstrate that the preferential attachment principle still holds for the power-law relation between ligands and proteins. We also found that polar molecular surface area, H-bond acceptor counts, H-bond donor counts and partition coefficient are potential factors to discriminate ligands from ordinary molecules and to differentiate super ligands (shared by three or more folds) from others. CONCLUSION: These findings have significant implications for evolution and drug discovery. First, the chronology of ligand-protein binding can be inferred by the power-law feature of ligand-protein mapping. Some nucleotide-containing ligands, such as ATP, ADP, GDP, NAD, FAD, dihydro-nicotinamide-adenine-dinucleotide phosphate (NDP), nicotinamide-adenine-dinucleotide phosphate (NAP), flavin mononucleotide (FMN) and AMP, are found to be the earliest cofactors bound to proteins, agreeing with the current understanding of evolutionary history. Second, the finding that about 30% of ligands are shared by two or more domains will help with drug discovery, such as in finding new functions from old drugs, developing promiscuous drugs and depending more on natural products. PMID- 17727708 TI - Thyroid hormone receptor orthologues from invertebrate species with emphasis on Schistosoma mansoni. AB - BACKGROUND: Thyroid hormone receptors (TRs) function as molecular switches in response to thyroid hormone to regulate gene transcription. TRs were previously believed to be present only in chordates. RESULTS: We isolated two TR genes from the Schistosoma mansoni and identified TR orthologues from other invertebrates: the platyhelminths, S. japonium and Schmidtea mediterranea, the mollusc, Lottia gigantean and the arthropod Daphnia pulex. Phylogenetic analysis of the DNA binding domain and/or ligand binding domain shows that invertebrate and vertebrate TRs cluster together, TRs from the vertebrates and from the jawless vertebrate (lamprey) clustered within separate subgroups, Platyhelminth TRs cluster outside of the vertebrate TR subgroups and that the schistosome TRs and S. mediterranea TRs clustered within separate subgroups. Alignment of the C terminus of the A/B domain revealed a conserved TR-specific motif, termed TR 'N terminus signature sequence', with a consensus sequence of (G/P)YIPSY(M/L)XXXGPE(D/E)X. Heterodimer formation between S. mansoni TRs and SmRXR1 suggests that the invertebrate TR protein gained the ability to form a heterodimer with RXR. ESMA analysis showed that SmTR alpha could bind to a conserved DNA core motif as a monomer or homodimer. CONCLUSION: Vertebrate TR genes originated from a common ancestor of the Bilateria. TR genes underwent duplication independently in the Protostomia and Deuterostomia. The duplication of TRs in deuterostomes occurred after the split of jawless and jawed vertebrates. In protostomes, TR genes underwent duplication in Platyhelminths, occurring independently in trematode and turbellarian lineages. Using S. mansoni TRs as an example, invertebrate TRs exhibited the ability to form a dimer with RXR prior to the emergence of the vertebrate TRs and were able to bind to vertebrate TR core DNA elements as a monomer or homodimer. PMID- 17727711 TI - Overabundant milk supply: an alternative way to intervene by full drainage and block feeding. AB - BACKGROUND: Too much or too little milk production are common problems in a lactation consultant's practice. Whereas underproduction is widely discussed in the lactation literature, overabundant milk supply is not. In my practice I work with women who experience moderate to severe oversupply syndrome. In most cases the syndrome can be successfully treated with full removal of milk followed by unilateral breastfeeding ad lib with the same breast offered at every breastfeed in a certain time block ("block feeding"). CASE PRESENTATIONS: Four cases of over supply of breast milk are presented. The management and outcome of each case is described. CONCLUSION: Overabundant milk supply is an often under-diagnosed condition in otherwise healthy lactating women. Full drainage and "block feeding" offer an adequate and userfriendly way to normalize milk production and treat symptoms in both mother and child. PMID- 17727709 TI - Comparative genomic analysis of the Tribolium immune system. AB - BACKGROUND: Tribolium castaneum is a species of Coleoptera, the largest and most diverse order of all eukaryotes. Components of the innate immune system are hardly known in this insect, which is in a key phylogenetic position to inform us about genetic innovations accompanying the evolution of holometabolous insects. We have annotated immunity-related genes and compared them with homologous molecules from other species. RESULTS: Around 300 candidate defense proteins are identified based on sequence similarity to homologs known to participate in immune responses. In most cases, paralog counts are lower than those of Drosophila melanogaster or Anopheles gambiae but are substantially higher than those of Apis mellifera. The genome contains probable orthologs for nearly all members of the Toll, IMD, and JAK/STAT pathways. While total numbers of the clip domain serine proteinases are approximately equal in the fly (29), mosquito (32) and beetle (30), lineage-specific expansion of the family is discovered in all three species. Sixteen of the thirty-one serpin genes form a large cluster in a 50 kb region that resulted from extensive gene duplications. Among the nine Toll like proteins, four are orthologous to Drosophila Toll. The presence of scavenger receptors and other related proteins indicates a role of cellular responses in the entire system. The structures of some antimicrobial peptides drastically differ from those in other orders of insects. CONCLUSION: A framework of information on Tribolium immunity is established, which may serve as a stepping stone for future genetic analyses of defense responses in a nondrosophiline genetic model insect. PMID- 17727710 TI - Oligomerization of the human immunodeficiency virus type 1 (HIV-1) Vpu protein--a genetic, biochemical and biophysical analysis. AB - BACKGROUND: The human immunodeficiency virus type 1(HIV-1) is a complex retrovirus and the causative agent of acquired immunodeficiency syndrome (AIDS). The HIV-1 Vpu protein is an oligomeric integral membrane protein essential for particle release, viral load and CD4 degradation. In silico models show Vpu to form pentamers with an ion channel activity. RESULTS: Using Vpu proteins from a primary subtype C and the pNL4-3 subtype B isolates of HIV-1, we show oligomerization of the full-length protein as well as its transmembrane (TM) domain by genetic, biochemical and biophysical methods. We also provide direct evidence of the presence of Vpu pentamers in a stable equilibrium with its monomers in vitro. This was also true for the TM domain of Vpu. Confocal microscopy localized Vpu to the endoplasmic reticulum and Golgi regions of the cell, as well as to post-Golgi vesicles. In fluorescence resonance energy transfer (FRET) experiments in live cells we show that Vpu oligomerizes in what appears to be either the Golgi region or intracellular vesicles, but not in the ER. CONCLUSION: We provide here direct evidence that the TM domain, is critical for Vpu oligomerization and the most favourable channel assembly is a pentamer. The Vpu oligomerization appears to be either the Golgi region or intracellular vesicles, but not in the ER. PMID- 17727712 TI - Re-evaluation of pulmonary titanium dioxide nanoparticle distribution using the "relative deposition index": Evidence for clearance through microvasculature. AB - BACKGROUND: Translocation of nanoparticles (NP) from the pulmonary airways into other pulmonary compartments or the systemic circulation is controversially discussed in the literature. In a previous study it was shown that titanium dioxide (TiO2) NP were "distributed in four lung compartments (air-filled spaces, epithelium/endothelium, connective tissue, capillary lumen) in correlation with compartment size". It was concluded that particles can move freely between these tissue compartments. To analyze whether the distribution of TiO2 NP in the lungs is really random or shows a preferential targeting we applied a newly developed method for comparing NP distributions. METHODS: Rat lungs exposed to an aerosol containing TiO2 NP were prepared for light and electron microscopy at 1 h and at 24 h after exposure. Numbers of TiO2 NP associated with each compartment were counted using energy filtering transmission electron microscopy. Compartment size was estimated by unbiased stereology from systematically sampled light micrographs. Numbers of particles were related to compartment size using a relative deposition index and chi-squared analysis. RESULTS: Nanoparticle distribution within the four compartments was not random at 1 h or at 24 h after exposure. At 1 h the connective tissue was the preferential target of the particles. At 24 h the NP were preferentially located in the capillary lumen. CONCLUSION: We conclude that TiO2 NP do not move freely between pulmonary tissue compartments, although they can pass from one compartment to another with relative ease. The residence time of NP in each tissue compartment of the respiratory system depends on the compartment and the time after exposure. It is suggested that a small fraction of TiO2 NP are rapidly transported from the airway lumen to the connective tissue and subsequently released into the systemic circulation. PMID- 17727714 TI - Child and adolescent psychiatric patients and later criminality. AB - BACKGROUND: Sweden has an extensive child and adolescent psychiatric (CAP) research tradition in which longitudinal methods are used to study juvenile delinquency. Up to the 1980s, results from descriptions and follow-ups of cohorts of CAP patients showed that children's behavioural disturbances or disorders and school problems, together with dysfunctional family situations, were the main reasons for families, children, and youth to seek help from CAP units. Such factors were also related to registered criminality and registered alcohol and drug abuse in former CAP patients as adults. This study investigated the risk for patients treated 1975-1990 to be registered as criminals until the end of 2003. METHODS: A regional sample of 1,400 former CAP patients, whose treatment occurred between 1975 and 1990, was followed to 2003, using database-record links to the Register of Persons Convicted of Offences at the National Council for Crime Prevention (NCCP). RESULTS: Every third CAP patient treated between 1975 and 1990 (every second man and every fifth woman) had entered the Register of Persons Convicted of Offences during the observation period, which is a significantly higher rate than the general population. CONCLUSION: Results were compared to published results for CAP patients who were treated between 1953 and 1955 and followed over 20 years. Compared to the group of CAP patients from the 1950s, the results indicate that the risk for boys to enter the register for criminality has doubled and for girls, the risk seems to have increased sevenfold. The reasons for this change are discussed. Although hypothetical and perhaps speculative this higher risk of later criminality may be the result of lack of social control due to (1) rising consumption of alcohol, (2) changes in organisation of child social welfare work, (3) the school system, and (4) CAP methods that were implemented since 1970. PMID- 17727713 TI - Cis sequence effects on gene expression. AB - BACKGROUND: Sequence and transcriptional variability within and between individuals are typically studied independently. The joint analysis of sequence and gene expression variation (genetical genomics) provides insight into the role of linked sequence variation in the regulation of gene expression. We investigated the role of sequence variation in cis on gene expression (cis sequence effects) in a group of genes commonly studied in cancer research in lymphoblastoid cell lines. We estimated the proportion of genes exhibiting cis sequence effects and the proportion of gene expression variation explained by cis sequence effects using three different analytical approaches, and compared our results to the literature. RESULTS: We generated gene expression profiling data at N = 697 candidate genes from N = 30 lymphoblastoid cell lines for this study and used available candidate gene resequencing data at N = 552 candidate genes to identify N = 30 candidate genes with sufficient variance in both datasets for the investigation of cis sequence effects. We used two additive models and the haplotype phylogeny scanning approach of Templeton (Tree Scanning) to evaluate association between individual SNPs, all SNPs at a gene, and diplotypes, with log transformed gene expression. SNPs and diplotypes at eight candidate genes exhibited statistically significant (p < 0.05) association with gene expression. Using the literature as a "gold standard" to compare 14 genes with data from both this study and the literature, we observed 80% and 85% concordance for genes exhibiting and not exhibiting significant cis sequence effects in our study, respectively. CONCLUSION: Based on analysis of our results and the extant literature, one in four genes exhibits significant cis sequence effects, and for these genes, about 30% of gene expression variation is accounted for by cis sequence variation. Despite diverse experimental approaches, the presence or absence of significant cis sequence effects is largely supported by previously published studies. PMID- 17727715 TI - The topology of metabolic isotope labeling networks. AB - BACKGROUND: Metabolic Flux Analysis (MFA) based on isotope labeling experiments (ILEs) is a widely established tool for determining fluxes in metabolic pathways. Isotope labeling networks (ILNs) contain all essential information required to describe the flow of labeled material in an ILE. Whereas recent experimental progress paves the way for high-throughput MFA, large network investigations and exact statistical methods, these developments are still limited by the poor performance of computational routines used for the evaluation and design of ILEs. In this context, the global analysis of ILN topology turns out to be a clue for realizing large speedup factors in all required computational procedures. RESULTS: With a strong focus on the speedup of algorithms the topology of ILNs is investigated using graph theoretic concepts and algorithms. A rigorous determination of all cyclic and isomorphic subnetworks, accompanied by the global analysis of ILN connectivity is performed. Particularly, it is proven that ILNs always brake up into a large number of small strongly connected components (SCCs) and, moreover, there are natural isomorphisms between many of these SCCs. All presented techniques are universal, i.e. they do not require special assumptions on the network structure, bidirectionality of fluxes, measurement configuration, or label input. The general results are exemplified with a practically relevant metabolic network which describes the central metabolism of E. coli comprising 10390 isotopomer pools. CONCLUSION: Exploiting the topological features of ILNs leads to a significant speedup of all universal algorithms for ILE evaluation. It is proven in theory and exemplified with the E. coli example that a speedup factor of about 1000 compared to standard algorithms is achieved. This widely opens the door for new high performance algorithms suitable for high throughput applications and large ILNs. Moreover, for the first time the global topological analysis of ILNs allows to comprehensively describe and understand the general patterns of label flow in complex networks. This is an invaluable tool for the structural design of new experiments and the interpretation of measured data. PMID- 17727716 TI - Pupal remodeling and the evolution and development of alternative male morphologies in horned beetles. AB - BACKGROUND: How novel morphological traits originate and diversify represents a major frontier in evolutionary biology. Horned beetles are emerging as an increasingly popular model system to explore the genetic, developmental, and ecological mechanisms, as well as the interplay between them, in the genesis of novelty and diversity. The horns of beetles originate during a rapid growth phase during the prepupal stage of larval development. Differential growth during this period is either implicitly or explicitly assumed to be the sole mechanism underlying differences in horn expression within and between species. Here I focus on male horn dimorphisms, a phenomenon at the center of many studies in behavioral ecology and evolutionary development, and quantify the relative contributions of a previously ignored developmental process, pupal remodeling, to the expression of male dimorphism in three horned beetle species. RESULTS: Prepupal growth is not the only determinant of differences in male horn expression. Instead, following their initial prepupal growth phase, beetles may be extensively remodeled during the subsequent pupal stage in a sex and size dependent manner. Specifically, male dimorphism in the three Onthophagus species studied here was shaped not at all, partly or entirely by such pupal remodeling rather than differential growth, suggesting that pupal remodeling is phylogenetically widespread, evolutionarily labile, and developmentally flexible. CONCLUSION: This study is the first to document that male dimorphism in horned beetles is the product of two developmentaly dissociated processes: prepupal growth and pupal remodeling. More generally, adult morphology alone appears to provide few clues, if any, as to the relative contributions of both processes to the expression of alternative male morphs, underscoring the importance of developmental studies in efforts aimed at understanding the evolution of adult diversity patterns. PMID- 17727717 TI - Vestibular signal processing in a subject with somatosensory deafferentation: the case of sitting posture. AB - BACKGROUND: The vestibular system of the inner ear provides information about head translation/rotation in space and about the orientation of the head with respect to the gravitoinertial vector. It also largely contributes to the control of posture through vestibulospinal pathways. Testing an individual severely deprived of somatosensory information below the nose, we investigated if equilibrium can be maintained while seated on the sole basis of this information. RESULTS: Although she was unstable, the deafferented subject (DS) was able to remain seated with the eyes closed in the absence of feet, arm and back supports. However, with the head unconsciously rotated towards the left or right shoulder, the DS's instability markedly increased. Small electrical stimulations of the vestibular apparatus produced large body tilts in the DS contrary to control subjects who did not show clear postural responses to the stimulations. CONCLUSION: The results of the present experiment show that in the lack of vision and somatosensory information, vestibular signal processing allows the maintenance of an active sitting posture (i.e. without back or side rests). When head orientation changes with respect to the trunk, in the absence of vision, the lack of cervical information prevents the transformation of the head-centered vestibular information into a trunk-centered frame of reference of body motion. For the normal subjects, this latter frame of reference enables proper postural adjustments through vestibular signal processing, irrespectively of the orientation of the head with respect to the trunk. PMID- 17727718 TI - Versatile annotation and publication quality visualization of protein complexes using POLYVIEW-3D. AB - BACKGROUND: Macromolecular visualization as well as automated structural and functional annotation tools play an increasingly important role in the post genomic era, contributing significantly towards the understanding of molecular systems and processes. For example, three dimensional (3D) models help in exploring protein active sites and functional hot spots that can be targeted in drug design. Automated annotation and visualization pipelines can also reveal other functionally important attributes of macromolecules. These goals are dependent on the availability of advanced tools that integrate better the existing databases, annotation servers and other resources with state-of-the-art rendering programs. RESULTS: We present a new tool for protein structure analysis, with the focus on annotation and visualization of protein complexes, which is an extension of our previously developed POLYVIEW web server. By integrating the web technology with state-of-the-art software for macromolecular visualization, such as the PyMol program, POLYVIEW-3D enables combining versatile structural and functional annotations with a simple web-based interface for creating publication quality structure rendering, as well as animated images for Powerpoint, web sites and other electronic resources. The service is platform independent and no plug-ins are required. Several examples of how POLYVIEW-3D can be used for structural and functional analysis in the context of protein-protein interactions are presented to illustrate the available annotation options. CONCLUSION: POLYVIEW-3D server features the PyMol image rendering that provides detailed and high quality presentation of macromolecular structures, with an easy to use web-based interface. POLYVIEW-3D also provides a wide array of options for automated structural and functional analysis of proteins and their complexes. Thus, the POLYVIEW-3D server may become an important resource for researches and educators in the fields of protein science and structural bioinformatics. The new server is available at http://polyview.cchmc.org/polyview3d.html. PMID- 17727720 TI - Blood genomic profiles of exposures to Venezuelan equine encephalitis in Cynomolgus macaques (Macaca fascicularis). AB - BACKGROUND: Lymphocytes provide invaluable whistle blowers of changes due to infections. We use the information registered by these cells using their mRNAs as they encounter the pathogen to develop patterns of expression that correspond to that specific pathogen. Venezuelan equine encephalitis (VEE) is a mosquito-borne viral disease characterized by fever and one or more of the following: severe headache, back pain, myalgias, prostration, chills, nausea, vomiting, weakness and other flu-like symptoms. Screening for host mRNA obtained from blood samples after exposure to VEEV may provide the means for early detection of surrogate markers of the impending illness and provide appropriate strategies for treatment. RESULTS: We have been carrying out gene expression analysis of PBMC exposed to VEEV to extract signatures and diagnostic markers of early exposure to be used in non invasive blood analysis methods. In this study, we used high throughput gene expression analysis to identify markers of early and late exposures to VEEV in vivo in Cynomolgus macaques (Macaca fascicularis). We carried out cDNA microarrays and real time PCR on blood samples obtained from the NHP model resulting in a panel of host genes that are altered in response to VEEV. CONCLUSION: Screening for host mRNA obtained from blood samples after exposure to VEEV may provide the means for early detection of surrogate markers of the impending illness and provide appropriate strategies for treatment. PMID- 17727719 TI - Effect of active smoking on the human bronchial epithelium transcriptome. AB - BACKGROUND: Lung cancer is the most common cause of cancer-related deaths. Tobacco smoke exposure is the strongest aetiological factor associated with lung cancer. In this study, using serial analysis of gene expression (SAGE), we comprehensively examined the effect of active smoking by comparing the transcriptomes of clinical specimens obtained from current, former and never smokers, and identified genes showing both reversible and irreversible expression changes upon smoking cessation. RESULTS: Twenty-four SAGE profiles of the bronchial epithelium of eight current, twelve former and four never smokers were generated and analyzed. In total, 3,111,471 SAGE tags representing over 110 thousand potentially unique transcripts were generated, comprising the largest human SAGE study to date. We identified 1,733 constitutively expressed genes in current, former and never smoker transcriptomes. We have also identified both reversible and irreversible gene expression changes upon cessation of smoking; reversible changes were frequently associated with either xenobiotic metabolism, nucleotide metabolism or mucus secretion. Increased expression of TFF3, CABYR, and ENTPD8 were found to be reversible upon smoking cessation. Expression of GSK3B, which regulates COX2 expression, was irreversibly decreased. MUC5AC expression was only partially reversed. Validation of select genes was performed using quantitative RT-PCR on a secondary cohort of nine current smokers, seven former smokers and six never smokers. CONCLUSION: Expression levels of some of the genes related to tobacco smoking return to levels similar to never smokers upon cessation of smoking, while expression of others appears to be permanently altered despite prolonged smoking cessation. These irreversible changes may account for the persistent lung cancer risk despite smoking cessation. PMID- 17727721 TI - A statistical method to incorporate biological knowledge for generating testable novel gene regulatory interactions from microarray experiments. AB - BACKGROUND: The incorporation of prior biological knowledge in the analysis of microarray data has become important in the reconstruction of transcription regulatory networks in a cell. Most of the current research has been focused on the integration of multiple sets of microarray data as well as curated databases for a genome scale reconstruction. However, individual researchers are more interested in the extraction of most useful information from the data of their hypothesis-driven microarray experiments. How to compile the prior biological knowledge from literature to facilitate new hypothesis generation from a microarray experiment is the focus of this work. We propose a novel method based on the statistical analysis of reported gene interactions in PubMed literature. RESULTS: Using Gene Ontology (GO) Molecular Function annotation for reported gene regulatory interactions in PubMed literature, a statistical analysis method was proposed for the derivation of a likelihood of interaction (LOI) score for a pair of genes. The LOI-score and the Pearson correlation coefficient of gene profiles were utilized to check if a pair of query genes would be in the above specified interaction. The method was validated in the analysis of two gene sets formed from the yeast Saccharomyces cerevisiae cell cycle microarray data. It was found that high percentage of identified interactions shares GO Biological Process annotations (39.5% for a 102 interaction enriched gene set and 23.0% for a larger 999 cyclically expressed gene set). CONCLUSION: This method can uncover novel biologically relevant gene interactions. With stringent confidence levels, small interaction networks can be identified for further establishment of a hypothesis testable by biological experiment. This procedure is computationally inexpensive and can be used as a preprocessing procedure for screening potential biologically relevant gene pairs subject to the analysis with sophisticated statistical methods. PMID- 17727722 TI - Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients. AB - BACKGROUND: The presence of HIV-1 preintegration reservoir was assessed in an in vitro experimental model of latent HIV-1 infection, and in patients treated or not with highly active antiretroviral therapy (HAART). RESULTS: In resting CD4+ T lymphocytes latently infected in vitro with HIV-1, we demonstrated that the polyclonal activation induced a HIV-1 replication, which could be prevented by the use of an HIV-1 integrase inhibitor. We also showed that this reservoir was labile since the rescuable HIV-1-antigens production from unintegrated HIV-1 genomes declined over time. These data confirm that our experimental approach allows the characterization of a functional unintegrated HIV-1 reservoir. We then explored the preintegration reservoir in HIV-1-infected patients. This reservoir was detected in 11 of 12 untreated patients, in 4 of 10 sustained responders to HAART, and in one incomplete responder. This reservoir was also inducible, labile, and anti-HIV-1 integrase drug inhibited its induction. Finally, this reservoir was associated with the presence of spontaneous HIV-1 antigens producing CD4+ T cells in blood from 3 of 3 untreated patients and 2 of 2 sustained responders to HAART harboring a preintegration reservoir. CONCLUSION: This preintegration phase of HIV-1 latency could be a consequence of the ongoing viral replication in untreated patients and of a residual viral replication in treated patients. PMID- 17727723 TI - Model-based analysis of two-color arrays (MA2C). AB - A novel normalization method based on the GC content of probes is developed for two-color tiling arrays. The proposed method, together with robust estimates of the model parameters, is shown to perform superbly on published data sets. A robust algorithm for detecting peak regions is also formulated and shown to perform well compared to other approaches. The tools have been implemented as a stand-alone Java program called MA2C, which can display various plots of statistical analysis for quality control. PMID- 17727725 TI - Comparison of a nurse initiated insulin infusion protocol for intensive insulin therapy between adult surgical trauma, medical and coronary care intensive care patients. AB - BACKGROUND: Sustained hyperglycemia is a known risk factor for adverse outcomes in critically ill patients. The specific aim was to determine if a nurse initiated insulin infusion protocol (IIP) was effective in maintaining blood glucose values (BG) within a target goal of 100-150 mg/dL across different intensive care units (ICUs) and to describe glycemic control during the 48 hours after protocol discontinuation. METHODS: A descriptive, retrospective review of 366 patients having 28,192 blood glucose values in three intensive care units, Surgical Trauma Intensive Care Unit (STICU), Medical (MICU) and Coronary Care Unit (CCU) in a quaternary care hospital was conducted. Patients were > 15 years of age, admitted to STICU (n = 162), MICU (n = 110) or CCU (n = 94) over 8 months; October 2003-June 2004 and who had an initial blood glucose level > 150 mg/dL. We summarized the effectiveness and safety of a nurse initiated IIP, and compared these endpoints among STICU, MICU and CCU patients. RESULTS: The median blood glucose values (mg/dL) at initiation of insulin infusion protocol were lower in STICU (188; IQR, 162-217) than in MICU, (201; IQR, 170-268) and CCU (227; IQR, 178-313); p < 0.0001. Mean time to achieving a target glucose level (100-150 mg/dL) was similar between the three units: 4.6 hours in STICU, 4.7 hours in MICU and 4.9 hours in CCU (p = 0.27). Hypoglycemia (BG < 60 mg/dL) occurred in 7% of STICU, 5% of MICU, and 5% of CCU patients (p = 0.85). Protocol violations were uncommon in all three ICUs. Mean blood glucose 48 hours following IIP discontinuation was significantly different for each population: 142 mg/dL in STICU, 167 mg/dL in MICU, and 160 mg/dL in CCU (p < 0.0001). CONCLUSION: The safety and effectiveness of nurse initiated IIP was similar across different ICUs in our hospital. Marked variability in glucose control after the protocol discontinuation suggests the need for further research regarding glucose control in patients transitioning out of the ICU. PMID- 17727724 TI - PERK eIF2 alpha kinase is required to regulate the viability of the exocrine pancreas in mice. AB - BACKGROUND: Deficiency of the PERK eIF2 alpha kinase in humans and mice results in postnatal exocrine pancreatic atrophy as well as severe growth and metabolic anomalies in other organs and tissues. To determine if the exocrine pancreatic atrophy is due to a cell-autonomous defect, the Perk gene was specifically ablated in acinar cells of the exocrine pancreas in mice. RESULTS: We show that expression of PERK in the acinar cells is required to maintain their viability but is not required for normal protein synthesis and secretion. Exocrine pancreatic atrophy in PERK-deficient mice was previously attributed to uncontrolled ER-stress followed by apoptotic cell death based on studies in cultured fibroblasts. However, we have found no evidence for perturbations in the endoplasmic reticulum or ER-stress and show that acinar cells succumb to a non apoptotic form of cell death, oncosis, which is associated with a pronounced inflammatory response and induction of the pancreatitis stress response genes. We also show that mice carrying a knockout mutation of PERK's downstream target, ATF4, exhibit pancreatic deficiency caused by developmental defects and that mice ablated for ATF4's transcriptional target CHOP have a normal exocrine pancreas. CONCLUSION: We conclude that PERK modulates secretory capacity of the exocrine pancreas by regulating cell viability of acinar cells. PMID- 17727726 TI - Anithrombotic prevention in vascular disease: bases for a new strategy in antithrombotic therapy. AB - A tendency toward bleeding often undercuts the beneficial preventive effect of higher doses of a single antithrombotic drug or combined antithrombotic therapy. Although high doses of antithrombotic drugs may be necessary for optimal prevention, such therapy can also elicit more frequent bleeding. Although major bleeding could be a reversible event is likely to lead clinicians to discontinue antithrombotic therapy which in turn could increase the risk of myocardial infarction, stroke, and cardiovascular death. Thus, to prevent thrombotic events without frequent bleeding complications, the preferred approach might be to use anti-inflammatory drugs in addition to the first-line antithrombotic drugs to reduce inflammation and thrombin formation in atheroma. Although some preliminary data have been already published, to confirm the potential benefit of anti inflammatory drugs in acute coronary syndromes large prospective double-bind randomized trials are necessary. PMID- 17727727 TI - Transposable element distribution, abundance and role in genome size variation in the genus Oryza. AB - BACKGROUND: The genus Oryza is composed of 10 distinct genome types, 6 diploid and 4 polyploid, and includes the world's most important food crop - rice (Oryza sativa [AA]). Genome size variation in the Oryza is more than 3-fold and ranges from 357 Mbp in Oryza glaberrima [AA] to 1283 Mbp in the polyploid Oryza ridleyi [HHJJ]. Because repetitive elements are known to play a significant role in genome size variation, we constructed random sheared small insert genomic libraries from 12 representative Oryza species and conducted a comprehensive study of the repetitive element composition, distribution and phylogeny in this genus. Particular attention was paid to the role played by the most important classes of transposable elements (Long Terminal Repeats Retrotransposons, Long interspersed Nuclear Elements, helitrons, DNA transposable elements) in shaping these genomes and in their contributing to genome size variation. RESULTS: We identified the elements primarily responsible for the most strikingly genome size variation in Oryza. We demonstrated how Long Terminal Repeat retrotransposons belonging to the same families have proliferated to very different extents in various species. We also showed that the pool of Long Terminal Repeat Retrotransposons is substantially conserved and ubiquitous throughout the Oryza and so its origin is ancient and its existence predates the speciation events that originated the genus. Finally we described the peculiar behavior of repeats in the species Oryza coarctata [HHKK] whose placement in the Oryza genus is controversial. CONCLUSION: Long Terminal Repeat retrotransposons are the major component of the Oryza genomes analyzed and, along with polyploidization, are the most important contributors to the genome size variation across the Oryza genus. Two families of Ty3-gypsy elements (RIRE2 and Atlantys) account for a significant portion of the genome size variations present in the Oryza genus. PMID- 17727728 TI - Attitudes, understanding, and concerns regarding medical research amongst Egyptians: a qualitative pilot study. AB - BACKGROUND: Medical research must involve the participation of human subjects. Knowledge of patients' perspectives and concerns with their involvement in research would enhance recruitment efforts, improve the informed consent process, and enhance the overall trust between patients and investigators. Several studies have examined the views of patients from Western countries. There is limited empirical research involving the perspectives of individuals from developing countries. The purpose of this study is to examine the attitudes of Egyptian individuals toward medical research. Such information would help clarify the type and extent of concerns regarding research participation of individuals from cultural, economic, and political backgrounds that differ from those in developed countries. METHODS: We conducted semi-structured interviews with 15 Egyptian individuals recruited from the outpatient settings (public and private) at Ain Shams University in Cairo, Egypt. Interviews were taped, transcribed, and translated. Thematic analysis followed. RESULTS: All individuals valued the importance of medical research; however most would not participate in research that involved more than minimal risk. Individuals were comfortable with studies involving surveys and blood sampling, but many viewed drug trials as being too risky. All participants valued the concept of informed consent, as they thought that their permission to be in a research study was paramount. Many participants had discomfort with or difficulty in the understanding several research concepts: randomization, double-blind, and clinical equipoise. Trust in the physicians performing research was important in deciding to participate in clinical research. The small sample size and the selection bias associated with obtaining information from only those who agreed to participate in a research study represent limitations in this study. CONCLUSION: Overall, individuals in our sample recognize the value of medical research and have a great deal of trust regarding medical research and their participation in research. There were, however, concerns with the level of research risks associated with several types of medical research. Many also demonstrated confusion with certain research methodologies. We recommend 1) enhanced educational efforts regarding general research concepts to enhance the validity of informed consent and 2) further survey studies in other areas of Egypt to determine the generalizability of our results. PMID- 17727729 TI - Targeting APOBEC3A to the viral nucleoprotein complex confers antiviral activity. AB - BACKGROUND: APOBEC3 (A3) proteins constitute a family of cytidine deaminases that provide intracellular resistance to retrovirus replication and to transposition of endogenous retroelements. A3A has significant homology to the C-terminus of A3G but has only a single cytidine deaminase active site (CDA), unlike A3G, which has a second N-terminal CDA previously found to be important for Vif sensitivity and virus encapsidation. A3A is packaged into HIV-1 virions but, unlike A3G, does not have antiviral properties. Here, we investigated the reason for the lack of A3A antiviral activity. RESULTS: Sequence alignment of A3G and A3A revealed significant homology of A3A to the C-terminal region of A3G. However, while A3G co-purified with detergent-resistant viral nucleoprotein complexes (NPC), virus associated A3A was highly detergent-sensitive leading us to speculate that the ability to assemble into NPC may be a property conveyed by the A3G N-terminus. To test this model, we constructed an A3G-3A chimeric protein, in which the N terminal half of A3G was fused to A3A. Interestingly, the A3G-3A chimera was packaged into HIV-1 particles and, unlike A3A, associated with the viral NPC. Furthermore, the A3G-3A chimera displayed strong antiviral activity against HIV-1 and was sensitive to inhibition by HIV-1 Vif. CONCLUSION: Our results suggest that the A3G N-terminal domain carries determinants important for targeting the protein to viral NPCs. Transfer of this domain to A3A results in A3A targeting to viral NPCs and confers antiviral activity. PMID- 17727730 TI - The sensitivity and specificity of four questions (HARK) to identify intimate partner violence: a diagnostic accuracy study in general practice. AB - BACKGROUND: Intimate partner violence (IPV) including physical, sexual and emotional violence, causes short and long term ill-health. Brief questions that reliably identify women experiencing IPV who present in clinical settings are a pre-requisite for an appropriate response from health services to this substantial public health problem. We estimated the sensitivity and specificity of four questions (HARK) developed from the Abuse Assessment screen, compared to a 30-item abuse questionnaire, the Composite Abuse Scale (CAS). METHODS: We administered the four HARK questions and the CAS to women approached by two researchers in general practice waiting rooms in Newham, east London. Inclusions: women aged more than 17 years waiting to see a doctor or nurse, who had been in an intimate relationship in the last year. EXCLUSIONS: women who were accompanied by children over four years of age or another adult, too unwell to complete the questionnaires, unable to understand English or unable to give informed consent. RESULTS: Two hundred and thirty two women were recruited. The response rate was 54%. The prevalence of current intimate partner violence, within the last 12 months, using the CAS cut off score of >or=3, was 23% (95% C.I. 17% to 28%) with pre-test odds of 0.3 (95% C.I. 0.2 to 0.4). The receiver operator characteristic curve demonstrated that a HARK cut off score of >or=1 maximises the true positives whilst minimising the false positives. The sensitivity of the optimal HARK cut-off score of >or=1 was 81% (95% C.I. 69% to 90%), specificity 95% (95% C.I. 91% to 98%), positive predictive value 83% (95% C.I. 70% to 91%), negative predictive value 94% (95% C.I. 90% to 97%), likelihood ratio 16 (95% C.I. 8 to 31) and post-test odds 5. CONCLUSION: The four HARK questions accurately identify women experiencing IPV in the past year and may help women disclose abuse in general practice. The HARK questions could be incorporated into the electronic medical record in primary care to prompt clinicians to ask about recent partner violence and to encourage disclosure by patients. Future research should test the effectiveness of HARK in clinical consultations. PMID- 17727731 TI - Association analysis of chromosome 1 migraine candidate genes. AB - BACKGROUND: Migraine with aura (MA) is a subtype of typical migraine. Migraine with aura (MA) also encompasses a rare severe subtype Familial Hemiplegic Migraine (FHM) with several known genetic loci. The type 2 FHM (FHM-2) susceptibility locus maps to chromosome 1q23 and mutations in the ATP1A2 gene at this site have recently been implicated. We have previously provided evidence of linkage of typical migraine (predominantly MA) to microsatellite markers on chromosome 1, in the 1q31 and 1q23 regions. In this study, we have undertaken a large genomic investigation involving candidate genes that lie within the chromosome 1q23 and 1q31 regions using an association analysis approach. METHODS: We have genotyped a large population of case-controls (243 unrelated Caucasian migraineurs versus 243 controls) examining a set of 5 single nucleotide polymorphisms (SNPs) and the Fas Ligand dinucleotide repeat marker, located within the chromosome 1q23 and 1q31 regions. RESULTS: Several genes have been studied including membrane protein (ATP 1 subtype A4 and FasL), cytoplasmic glycoprotein (CASQ 1) genes and potassium (KCN J9 and KCN J10) and calcium (CACNA1E) channel genes in 243 migraineurs (including 85% MA and 15% of migraine without aura (MO)) and 243 matched controls. After correction for multiple testing, chi-square results showed non-significant P values (P > 0.008) across all SNPs (and a CA repeat) tested in these different genes, however results with the KCN J10 marker gave interesting results (P = 0.02) that may be worth exploring further in other populations. CONCLUSION: These results do not show a significant role for the tested candidate gene variants and also do not support the hypothesis that a common chromosome 1 defective gene influences both FHM and the more common forms of migraine. PMID- 17727732 TI - Evolution of sociality by natural selection on variances in reproductive fitness: evidence from a social bee. AB - BACKGROUND: The Central Limit Theorem (CLT) is a statistical principle that states that as the number of repeated samples from any population increase, the variance among sample means will decrease and means will become more normally distributed. It has been conjectured that the CLT has the potential to provide benefits for group living in some animals via greater predictability in food acquisition, if the number of foraging bouts increases with group size. The potential existence of benefits for group living derived from a purely statistical principle is highly intriguing and it has implications for the origins of sociality. RESULTS: Here we show that in a social allodapine bee the relationship between cumulative food acquisition (measured as total brood weight) and colony size accords with the CLT. We show that deviations from expected food income decrease with group size, and that brood weights become more normally distributed both over time and with increasing colony size, as predicted by the CLT. Larger colonies are better able to match egg production to expected food intake, and better able to avoid costs associated with producing more brood than can be reared while reducing the risk of under-exploiting the food resources that may be available. CONCLUSION: These benefits to group living derive from a purely statistical principle, rather than from ecological, ergonomic or genetic factors, and could apply to a wide variety of species. This in turn suggests that the CLT may provide benefits at the early evolutionary stages of sociality and that evolution of group size could result from selection on variances in reproductive fitness. In addition, they may help explain why sociality has evolved in some groups and not others. PMID- 17727733 TI - Actions of N-arachidonyl-glycine in a rat inflammatory pain model. AB - BACKGROUND: While cannabinoid receptor agonists have analgesic activity in inflammatory pain states they produce a range of side effects. Recently, it has been demonstrated that the arachidonic acid-amino acid conjugate, N-arachidonyl glycine (NA-glycine) is effective in acute pain models. RESULTS: In the present study we examined the effect of NA-glycine in a rat model of inflammatory pain. Intrathecal administration of NA-glycine (70 - 700 nmol) and the pan-cannabinoid receptor agonist HU-210 (10 nmol) reduced the mechanical allodynia and thermal hyperalgesia induced by intraplantar injection of Freund's complete adjuvant (FCA). The actions of HU-210, but not NA-glycine were reduced by the cannabinoid CB1 receptor antagonist AM251. The cannabinoid CB2 receptor antagonist SR144528 also had no effect on the actions of NA-glycine. In contrast, N-arachidonyl-GABA (NA-GABA, 700 nmol) and N-arachidonyl-alanine (NA-alanine, 700 nmol) had no effect on allodynia and hyperalgesia. HU-210, but not NA-glycine produced a reduction in rotarod latency. CONCLUSION: These findings suggest that NA-glycine may provide a novel non-cannabinoid receptor mediated approach to alleviate inflammatory pain. PMID- 17727734 TI - Human immunodeficiency virus type 1 specific cytotoxic T lymphocyte responses in Chinese infected with HIV-1 B'/C Recombinant (CRF07_BC). AB - BACKGROUND: The characterization of HIV-1-specific T cell responses in people infected with locally circulating HIV-1 strain will facilitate the development of HIV-1 vaccine. Sixty intravenous drug users infected with HIV-1 circulating recombinant form 07_BC (CRF07_BC), which has been spreading rapidly in western China from north to south, were recruited from Xinjiang, China to assess the HIV 1-specific T cell responses at single peptide level with overlapping peptides (OLP) covering the whole concensus clades B and C proteome. RESULTS: The median of the total magnitude and total number of OLPs recognized by CTL responses were 10925 SFC/million PBMC and 25 OLPs, respectively, when tested by clade C peptides, which was significantly higher than when tested by clade B peptides. The immunodominant regions, which cover 14% (58/413) of the HIV-1 proteome, are widely distributed throughout the HIV-1 proteome except in Tat, Vpu and Pol-PR, with Gag, Pol-RT, Pol-Int and Nef being most frequently targeted. The subdominant epitopes are mostly located in p24, Nef, integrase, Vpr and Vif. Of the responses directed to clade C OLPs, 61.75% (972/1574) can be observed when tested with corresponding clade B OLPs. However, Pol-PR and Vpu tend to be targeted in the clade B sequence rather than the clade C sequence, which is in line with the recombinant pattern of CRF07_BC. Stronger and broader CTL responses in subjects with CD4 cell counts ranging from 200 to 400/mm3 were observed when compared to those with less than 200/mm3 or more than 400/mm3, though there have been no significant correlations identified between the accumulative CTL responses or overall breadth and CD4 cell count or plasma viral load. CONCLUSION: This is the first study conducted to comprehensively address T cell responses in Chinese subjects infected with HIV-1 CRF07_BC in which subtle differences in cross reactivity were observed, though similar patterns of overall immune responses were demonstrated with clade B infected populations. The immunodominant regions identified in this population can facilitate future HIV-1 vaccine development in China. PMID- 17727736 TI - Receptive (aural) vocabulary development in children with permanent bilateral sensorineural hearing impairment. AB - OBJECTIVE: The receptive (aural) vocabulary development of children with binaural aided residual hearing was investigated in a prospective longitudinal analysis (repeated measures). PATIENT AND METHODS: Thirty-three children with sensorineural hearing loss, without major co-morbidities (mean age at the first testing point, 56.2 months, standard deviation 19.0 months) were recruited from the 1994 German Goettinger Hearing Language Register. Their receptive vocabulary was measured using standardised tests (with reference to normal hearing child performance) on three separate test points (mean follow up, 18.7 months, standard deviation 5.0 months). RESULTS: On average, the study group scored below the normal range at the first and second tests and made a significant improvement at the last test. The degree of hearing loss was found to be significantly correlated to vocabulary performance at all time points, with increasing correlation coefficients. At the third test, significant predictive variables for successful receptive vocabulary outcome were found to be: degree of hearing loss (t = 5.43; p < 0.0001); age at diagnosis (t = 2.29; p = 0.03); and nonverbal intelligence (t = 2.82; p = 0.009). CONCLUSION: If permanent childhood hearing impairment is mild and/or is detected early, and if the child grows up in a monolingual environment, the development of receptive vocabulary within the normal range is possible. PMID- 17727735 TI - Revised genomic structure of the human ghrelin gene and identification of novel exons, alternative splice variants and natural antisense transcripts. AB - BACKGROUND: Ghrelin is a multifunctional peptide hormone expressed in a range of normal tissues and pathologies. It has been reported that the human ghrelin gene consists of five exons which span 5 kb of genomic DNA on chromosome 3 and includes a 20 bp non-coding first exon (20 bp exon 0). The availability of bioinformatic tools enabling comparative analysis and the finalisation of the human genome prompted us to re-examine the genomic structure of the ghrelin locus. RESULTS: We have demonstrated the presence of an additional novel exon (exon -1) and 5' extensions to exon 0 and 1 using comparative in silico analysis and have demonstrated their existence experimentally using RT-PCR and 5' RACE. A revised exon-intron structure demonstrates that the human ghrelin gene spans 7.2 kb and consists of six rather than five exons. Several ghrelin gene-derived splice forms were detected in a range of human tissues and cell lines. We have demonstrated ghrelin gene-derived mRNA transcripts that do not code for ghrelin, but instead may encode the C-terminal region of full-length preproghrelin (C ghrelin, which contains the coding region for obestatin) and a transcript encoding obestatin-only. Splice variants that differed in their 5' untranslated regions were also found, suggesting a role of these regions in the post transcriptional regulation of preproghrelin translation. Finally, several natural antisense transcripts, termed ghrelinOS (ghrelin opposite strand) transcripts, were demonstrated via orientation-specific RT-PCR, 5' RACE and in silico analysis of ESTs and cloned amplicons. CONCLUSION: The sense and antisense alternative transcripts demonstrated in this study may function as non-coding regulatory RNA, or code for novel protein isoforms. This is the first demonstration of putative obestatin and C-ghrelin specific transcripts and these findings suggest that these ghrelin gene-derived peptides may also be produced independently of preproghrelin. This study reveals several novel aspects of the ghrelin gene and suggests that the ghrelin locus is far more complex than previously recognised. PMID- 17727737 TI - Lateral skull base surgery: a complicated pursuit? AB - The management of lesions of the lateral skull base is a highly sophisticated branch of surgery generally performed by otolaryngology-head and neck surgeons as part of a multi-disciplinary team. Assessment of patients with diseases affecting the lateral skull base can be complex, as can the application of the various treatment modalities and the management of the expected and unexpected side effects of that treatment. A wide range of pathological conditions occur in the lateral skull base. Many operations and procedures have been described for dealing with them. There is not necessarily one correct solution to the management of any particular problem in the skull base, with multiple factors to be considered in planning and intervention. As surgeons, we need to know how our own results and outcomes compare with pooled, published data concerning the implications and complications occurring as a result of intervention, in order to better advise our patients on their management. PMID- 17727739 TI - Conversion to lamotrigine monotherapy from valproate monotherapy in older adolescent patients with epilepsy. AB - BACKGROUND: Pharmacokinetic interactions can make necessary anti-epileptic medication (AED) changes hazardous for children with epilepsy. We report the utility of a dosing algorithm designed to maintain stable trough lamotrigine (LTG) concentrations during conversion from valproate (VPA) to LTG monotherapy in adolescents aged 16-20 years. METHODS: Patients were enrolled into the study if they required a change in their AED regimen due to lack of efficacy or intolerable side effects. Conversion to LTG monotherapy took place in a four part treatment algorithm. Lamotrigine was escalated according to a target dose of 200 mg/day over 8-weeks. Valproate was withdrawn over a period of 2-6 weeks, depending on the initial dose. Lamotrigine dose was further escalated to 500 mg/day and continued for four weeks as mono therapy. Trough serum concentrations of LTG were measured during each phase of the trial. RESULTS: Twelve of 16 patients completed the study. After the LTG escalation to 200 mg/day, mean trough serum concentrations of 8.0 microg/mL did not differ significantly from the 9.5 microg/mL after VPA withdrawal or the 9.2 microg/mL after 4 weeks of monotherapy at 500 mg/day. Adverse events led to premature discontinuation for one subject. Two subjects withdrew due to worsening seizures during LTG monotherapy possibly due to non-compliance. Limitations of the trial include the open label design and small sample size of the sub-analysis. CONCLUSION: In adolescent patients, this algorithm produces stable LTG serum concentrations with favorable tolerability during a transition from VPA to LTG mono therapy. PMID- 17727738 TI - Suffering from dementia - the patient's perspective: a review of the literature. AB - BACKGROUND: Among the general public there is a deep fear of developing dementia, which has led to an increasing number of people "at risk" seeking ways (such as advance directives) to avoid undergoing progressive mental decline. The views of people with dementia are vital in obtaining a real answer to the question of how the disease affects people's lives and whether it actually involves the suffering that so many fear. METHOD: A review of the international literature is provided on what is known about living through dementia from the patient's perspective. RESULTS: A total of 50 papers met the inclusion criteria. The findings of these reviewed papers give insight into the impact of dementia and the ways that those who have it deal with its effects by using different coping strategies. The literature on the perspective of the patient gives no solid support to the widespread assumption that dementia is necessarily a state of dreadful suffering. Although the impact of dementia and the experiences of loss resulting in multiple "negative" emotions cannot be denied, our findings also indicate that people do not undergo the disease passively and use both emotion-oriented and problem oriented coping strategies to deal with its challenges. The experiences of living through dementia as told by the sufferers appear to yield a more subtle picture than the assumptions made by the general public. CONCLUSION: The overview provides a good starting point for improving the adjustment of care to the experience and wishes of people with dementia. PMID- 17727740 TI - Efficacy of vardenafil for the treatment of erectile dysfunction in men with hypertension: a meta-analysis of clinical trial data. AB - OBJECTIVE: To review the evidence evaluating the efficacy of vardenafil in subgroups of hypertensive patients with erectile dysfunction (ED). METHODS: Meta analysis of randomized, double-blinded, placebo-controlled, flexible-dose vardenafil clinical trials that were >or=12 weeks in duration evaluated men with a >or=6-month history of ED and required a >or=50% failure rate in baseline sexual attempts. The primary endpoints analyzed were the erectile function domain of the International Index of Erectile Function questionnaire (IIEF-EF) and Sexual Encounter Profile questions 2 (SEP2) and 3 (SEP3). RESULTS: Eight clinical trials were included (n = 2427 patients) consisting of 839 patients (35%) with a self-reported diagnosis of hypertension (HTN): 498 in the vardenafil and 341 in the placebo groups. Vardenafil's efficacy was evidenced by an average increase of 8.9 points in the IIEF-EF (95% CI: 7.4, 10.5) at week 12 compared to placebo, with individual trial values ranging from 16.4 to 26.1 and 11.3 to 17.8 for the vardenafil and placebo groups, respectively. Vardenafil also increased success rates for the ability to obtain erections (SEP2) by 32.4% (95% CI: 27.4%, 37.5%) over a 12-week timeframe compared to placebo, with individual trial values ranging from 57.2% to 92.2% for vardenafil and 32.0% to 66.9% for placebo. Similarly, success rates for the ability to maintain erections (SEP3) improved 38.0% (95% CI: 29.5%, 46.6%) compared to placebo, with individual trial values ranging from 41.7% to 88.2% for vardenafil and 20.5% to 51.4% for placebo. Vardenafil was equally efficacious in improving IIEF-EF, SEP2, and SEP3 in those with and without self-reported HTN. CONCLUSION: This meta-analysis demonstrated that vardenafil was significantly more efficacious than placebo for the treatment of ED in patients with comorbid HTN and offered similar treatment benefits in patients without HTN. PMID- 17727742 TI - The case of 'protective fever and chest signs': towards a better understanding of general practice databases. PMID- 17727743 TI - The Quality and Outcomes Framework: too early for a final verdict. PMID- 17727744 TI - Interpersonal continuity: old and new perspectives. PMID- 17727746 TI - Signs and symptoms for diagnosis of serious infections in children: a prospective study in primary care. AB - BACKGROUND: Serious infections in children (sepsis, meningitis, pneumonia, pyelonephritis, osteomyelitis, and cellulitis) are associated with considerable mortality and morbidity. In children with an acute illness, the primary care physician uses signs and symptoms to assess the probability of a serious infection and decide on further management. AIM: To analyse the diagnostic accuracy of signs and symptoms, and to create a multivariable triage instrument. DESIGN OF STUDY: A prospective diagnostic accuracy study. SETTING: Primary care in Belgium. METHOD: Children aged 0-16 years with an acute illness for a maximum of 5 days were included consecutively. Signs and symptoms were recorded and compared to the final outcome of these children (a serious infection for which hospitalisation was necessary). Accuracy was analysed bivariably. Multivariable triage instruments were constructed using classification and regression tree (CART) analysis. RESULTS: A total of 3981 children were included in the study, of which 31 were admitted to hospital with a serious infection (0.78%). Accuracy of signs and symptoms was fairly low. Classical textbook signs (meningeal irritation impaired peripheral circulation) had high specificity. The primary classification tree consisted of five knots and had sensitivity of 96.8% (95% confidence interval [CI] = 83.3 to 99.9), specificity 88.5% (95% CI = 87.5 to 89.5), positive predictive value 6.2% (95% CI = 4.2 to 8.7), and negative predictive value 100.0% (95% CI = 99.8 to 100.0), by which a serious infection can be excluded in children testing negative on the tree. The sign paramount in all trees was the physician's statement 'something is wrong'. CONCLUSION: Some individual signs have high specificity. A serious infection can be excluded based on a limited number of signs and symptoms. PMID- 17727745 TI - Validation of a clinical rule to predict complications of acute cough in preschool children: a prospective study in primary care. AB - BACKGROUND: Few clinical rules have been derived let alone validated in primary care. A rule was derived to predict complications of acute cough in preschool children presenting to primary care. The clinical rule used the presence/absence of fever and/or chest signs to distinguish children at low, medium, and high risk of complications. AIM: To validate a clinical rule for predicting complications of acute cough in preschool children in primary care. DESIGN OF STUDY: Prospective cohort study. SETTING: Thirteen general practices in Bristol and Tayside, UK. METHOD: Preschool children with cough up to 28 days and without asthma were recruited. The same sociodemographic, clinical history, examination, and complications data as for the derivation study were collected. First, univariable logistic regression was used to explore the associations with complications, and then predictors with stronger relationships (P<0.2) were modelled using multivariable logistic regression. These predictors were compared with derivation predictors with respect to their strength of association with complications. The derivation predictors were used in the validation dataset to allow comparison of the post-test probabilities of complications between derivation and validation studies. RESULTS: The presence of fever and chest signs in the validation study tended to be protective for complications, with univariable odds ratios (ORs) of 0.37 and 0.81 respectively, compared with ORs of 4.86 and 2.72 in the derivation study. However, 95% confidence limits were wide and evidence for two other possible reasons for these results were found: spectrum bias and confounding by indication. CONCLUSION: No evidence was found to validate the clinical rule for predicting complications of acute cough, possibly as a result of spectrum bias, confounding by indication, and/or chance. As paediatric infectious illness is costly and associated with high rates of antibiotic use, further research is needed to derive and validate prediction rules. PMID- 17727747 TI - Aetiology and prediction of pneumonia in lower respiratory tract infection in primary care. AB - BACKGROUND: Knowledge of predominant pathogens and their association with outcome are of importance for the management of lower respiratory tract infection (LRTI). As antibiotic therapy is indicated in pneumonia and not in acute bronchitis, a predictor of pneumonia is needed. AIM: To describe the aetiology and outcome of LRTI in adults with pneumonic and adults with non-pneumonic LRTI treated in general practice and to identify predictors of radiographic pneumonia. DESIGN OF STUDY: Prospective, observational study. SETTING: Forty-two general practices and an outpatient clinic at the Department of Infectious Diseases, Odense University Hospital, Denmark. METHOD: A total of 364 adults diagnosed with community acquired LRTI by their GP were studied with chest radiography, vital signs, biochemical markers of inflammation (C-reactive protein [CRP] and leukocyte count), and microbiological examinations. Primary outcome measure was hospitalisation within 4 weeks. RESULTS: Pneumonia was radiographically verified in 48 of 364 patients (13%). Bacterial infection was seen more often in patients with pneumonia (33% versus 17%, P<0.001), and viral infection more often in non pneumonic patients (26% versus 13%, P<0.05). Hospitalisation was more common in patients with pneumonia compared to non-pneumonic patients (19 versus 3%, P<0.001); and in patients with pneumococcal infection compared with patients without pneumococcal infection (26 versus 4%, P = 0.001). The positive predictive value of GPs' diagnosis of pneumonia was low (0.23), but the vital signs, CRP, and leukocyte count had comparably low positive predictive values (0.23-0.30). CONCLUSION: Streptococcus pneumoniae was the most common bacterial pathogen. The risk of hospitalisation was highest among patients with pneumonia or pneumococcal infection; this emphasises the importance of coverage of S. pneumoniae when treatment is indicated. CRP should not be introduced for diagnosis of radiographic pneumonia in general practice before its use has been investigated in prospective, controlled intervention trials using CRP-guided treatment algorithms. PMID- 17727748 TI - Procalcitonin versus C-reactive protein for predicting pneumonia in adults with lower respiratory tract infection in primary care. AB - BACKGROUND: The role of procalcitonin in diagnosing bacterial infection has mainly been studied in patients with severe infections. There is no study on the value of procalcitonin measurements in adults with lower respiratory tract infection (LRTI) treated in primary care. AIM: To evaluate the accuracy of plasma procalcitonin in predicting radiographic pneumonia, bacterial infection, and adverse outcome in a population of adults with LRTI treated in primary care. DESIGN OF STUDY: Prospective, observational study. SETTING: Forty-two general practices and an outpatient clinic at the Department of Infectious Diseases, Odense University Hospital, Denmark. METHOD: A total of 364 patients with LRTI were prospectively enrolled from 42 general practices. Patients were examined with chest radiography, microbiological analyses, and measurements of C-reactive protein (CRP) and procalcitonin. The outcome measure was hospitalisation within 4 weeks of enrollment. RESULTS: Median procalcitonin was 0.05 ng/ml, which was below the functional sensitivity of the assay (0.06 ng/ml). In predicting radiographic pneumonia, bacterial infection, and hospitalisation, the sensitivities of procalcitonin >0.06 ng/ml were 0.70, 0.51, and 0.67, and of CRP were > or =20 mg/l, 0.73, 0.56, and 0.74 respectively. Corresponding positive predictive values were between 0.09 and 0.28. CONCLUSION: Both procalcitonin >0.06 ng/ml and CRP > or =20 mg/l were associated with radiographic pneumonia, bacterial infection, and subsequent hospitalisation, but positive predictive values were too low for any of the two inflammatory markers to be of use in clinical practice. To measure procalcitonin values accurately in the primary care setting, a more sensitive method is needed, but there was no indication that procalcitonin is superior to CRP in identifying patients with pneumonia, bacterial aetiology, or adverse outcome. PMID- 17727749 TI - Illness behaviour and antibiotic prescription in patients with respiratory tract symptoms. AB - BACKGROUND: Although the vast majority of respiratory tract symptoms are self limiting, many patients visit their GP for these symptoms and antibiotics are over-prescribed. AIM: To explore determinants of patients visiting GPs for recent cough, sore throat, or earache; for being prescribed antibiotics; and for patients' satisfaction with visiting the GP. DESIGN OF THE STUDY: Second Dutch National Survey of General Practice (DNSGP-2) with a health interview and an additional questionnaire. SETTING: A total of 7057 adult patients of 163 GPs in the Netherlands. METHOD: Characteristics of patients and GPs as well as morbidity data were derived from the DNSGP-2 and a health interview. Characteristics of the symptoms, GPs' management and patients' satisfaction were measured by an additional written questionnaire. Data were analysed by means of multivariate logistic regression. RESULTS: About 40% of the responders (n = 1083) reported cough, sore throat, or earache in the 2 weeks preceding the interview and, of them, 250 visited their GP. Of this latter group, 97 patients were prescribed antibiotics. Apart from non-medical reasons, relevant medical factors played an important role in deciding to visit the GP. Smokers and patients with cardiac disease or diabetes mellitus were not especially inclined to see their GP. Smoking behaviour, fever, and views on respiratory tract symptoms and antibiotics of patients and GPs were associated with being prescribed antibiotics. Patients' perception of having been carefully examined was associated with their satisfaction, while receiving antibiotics was not. CONCLUSION: GPs should inform patients with clear elevated risk when to visit their GP in cases of cough, sore throat, or earache. There is still a need for GPs and patients to be better informed about the limited significance of single inflammation signs (for example, fever and green phlegm) as an indication for antibiotics. Careful examination of the patient contributes to patient satisfaction. PMID- 17727750 TI - Skin infections and antibiotic prescribing: a comparison of surveillance and prescribing data. AB - BACKGROUND: Reductions in the number of dispensed antibiotics and the incidence of respiratory infections presented to GPs and have been reported. Whether this trend applies to skin infections requires further investigation. AIM: To examine trends in the incidence of skin infections in relation to trends in dispensed prescriptions for flucloxacillin, topical fusidic acid, mupirocin, and corticosteroids with fusidic acid. DESIGN OF STUDY: Population-based analysis of patients presenting to GPs (1999-2005) contrasted with national prescribing data. SETTING: A sentinel practice network covering a population of 700,000 in England and Wales. METHOD: Quarterly incidence rates of skin infections and of impetigo reported over the years 1999-2005 were compared with quarterly data on dispensed prescriptions reported by the Prescription Pricing Authority for England. RESULTS: In children (aged 0-14 years) the incidence of skin infections decreased slightly between 1999 and 2003 and more sharply from 2004 to 2005. In adults (aged > or =15 years) incidence was reasonably constant from year to year. In every year examined, and in both age groups, there were autumnal incidence peaks. There were annual increases in dispensed prescriptions for flucloxacillin capsules, but there was little change in the use of flucloxacillin syrups and topical antibiotic prescriptions. All prescribing data sets showed increases in the third quarter: topical corticosteroids with fusidic acid were prescribed more frequently in summer than winter. CONCLUSION: In spite of slight reductions in the incidence of skin infections, flucloxacillin capsule-dispensed prescriptions have increased, suggesting that doctors have not limited their antibiotic prescribing behaviour for skin conditions. PMID- 17727751 TI - Results of a 12-month quality-circle prescribing improvement programme for GPs. AB - BACKGROUND: The impact of a quality-circle GP prescribing improvement programme, implemented in France in 2001-2002, was assessed by a controlled study. The study involved all 27 GPs of three semi-rural areas of Brittany, France. Practice data (overall prescribing cost and markers of prescribing efficiency) were collated in an intention-to-treat analysis, using the Mann-Whitney U test. Twenty-four GPs attended the meetings regularly. The reduction in drug expenditure exceeded the cost of the programme, although variations in size effects were observed among the settings. PMID- 17727752 TI - Vitamin D deficiency in multicultural primary care: a case series of 299 patients. AB - An increase in diagnoses of vitamin D deficiency prompted a review of cases from four general practices. Of the 299 cases identified, the predominant patient group comprised adult Somali females presenting with symptoms of chronic musculoskeletal pain. Women of childbearing age were particularly at risk. Known at-risk groups were not receiving supplementation. Significant clinical need appears not to be met in this population group and consideration of vitamin D deficiency during consultations is warranted. PMID- 17727753 TI - Mangin on QOF. PMID- 17727754 TI - Mangin on QOF. PMID- 17727755 TI - Mangin on QOF. PMID- 17727756 TI - Confidentiality on ward rounds. PMID- 17727757 TI - Mangin on QOF. PMID- 17727759 TI - Handshakes and dubious editing. PMID- 17727760 TI - Depression as chronic disease. PMID- 17727761 TI - Death certification. PMID- 17727769 TI - [Perioperative protection of blood]. PMID- 17727770 TI - [Perioperative protection of nerve]. PMID- 17727771 TI - [Perioperative protection of kidney]. PMID- 17727772 TI - [Perioperative protection of lung]. PMID- 17727773 TI - [Protective effects of ketamine on allergen-induced airway inflammatory injure and high airway reactivity in asthma: experiment with rats]. AB - OBJECTIVE: To observe the effects of ketamine on bronchial hyperresponsiveness and airway inflammation in equal asthma. METHODS: 56 Brown-Norway rats were randomly assigned to seven groups: negative control group (Group A), asthma model group (Group B) and inhalation groups with nebulized ketamine at different concentrations (Group C, D, E) and intraperitoneal injection groups with ketamine at different doses (Group F, G). The rats were sensitized by injection of ovalbumin (OVA) together with aluminum hydroxide and Bordetella pertussis as adjuvants, then challenged by repeated intermittent (thrice weekly) exposure to aerosolized OVA for two weeks. Before challenge, the sensitized rats were exposed to an aerosol of phosphate buffered saline (PBS) or ketamine at the concentrations of 12.5 mg/ml, 25 mg/ml and 50 mg/ml respectively in Groups B, C, D and E. The sensitized rats were intraperitoneally injected with ketamine at the doses of 50 microg/kg or 100 microg/kg respectively in Group F and G. The sensitized rats in Group A received phosphate buffered solution (PBS) by inhalation. The airway reactivity to acetylcholine (ACH) was assessed in vivo 24 hr after the last OVA challenge, then the lungs were removed for measurement of the mRNA and protein expression of iNOS and production of NO and lung sections for histopathologic examination. RESULTS: (1) In the OVA-sensitized and challenged rats, the dose-response curve of the expiratory resistance (Re) shifted to the upper-left +/- ward compared with that of PBS control rats. In addition, the provocation doses required to increase the Re by 100%, 200% and 400% for OVA-sensitized and challenged rats in Group B were significantly lower than those of the PBS control rats (14.65 +/- 1.19 vs 32.28 +/- 1.43, 15.17 +/- 1.19 vs 38.91 +/- 1.39, and 16.28 +/- 1.18 vs 56.53 +/- 1.38, all P < 0.01). The OVA-sensitized rats treated with ketamine before OVA challenge demonstrated a significant decrease in AHR by a rightward shift of the dose-response curves to ACH and significant higher provocation doses compared with that of the OVA control rats (P < 0.05). (2) Marked inflammatory changes in the airways of Group B were present, while obviously lessen inflammatory cell infiltration in peribronchial and perialveolar tissues and improved lung edema were observed in the groups treated with ketamine. (3) Quantitation by densitometry showed that the relative density of iNOS mRNA bands normalized to beta-actin was significantly higher in the OVA control than the PBS control (1.0 +/- 0.07 vs 0.48 +/- 0.07, P < 0.01). Treatment with ketamine significantly decreased the expression of iNOS mRNA in Group C (0.65 +/- 0.07), Group D (0.58 +/- 0.09), Group E (0.56 +/- 1.00), and Group F (0.66 +/- 0.06) when compared with Group B (all P < 0.05). (4) The relative iNOS protein levels (ratios of iNOS/beta-actin) determined by densitometry analysis showed a 4-fold increase in Group A compared with those in the negative group (0.54 +/- 0.08 vs 0.13 +/- 0.08, P < 0.05). When compared with those of the OVA control, the levels of relative iNOS protein expression showed a significant decrease in the lungs from the rats treated with ketamine inhalation at the doses of 12.5 mg/ml (0.20 +/- 0.03) and 25 mg/ml (0.18 +/- 0.03) and with ketamine and intraperitoneally the at dose of 50 microg/kg (0.21 +/- 0.04) (P < 0.05). (5) NO production in pulmonary tissues was significantly higher in the OVA-treated rats compared to the PBS controls (0.39 +/- 0.04 micromol/g protein vs 0.13 +/- 0.01 micromol/g protein, P < 0.01), but this OVA-triggered NO production was significantly decreased by treatment with 12.5 and 25 mg/ml inhaled ketamine (0.19 +/- 0.03 micromol/g and 0.17 +/- 0.03 micromol/g, both P < 0.05) and 50 microg/kg i.p.-injected ketamine (0.16 +/- 0.04 micromol/g, P < 0.05) when compared with the OVA-treated rats. CONCLUSION: Both inhalation and systemic administration of ketamine attenuate inflammatory the lung injury and airway hyperreactivity of the OVA-induced asthma model. The protective effects of ketamine is achieved by inhibiting OVA-provoked over expression of mRNA and protein of iNOS and reducing the production of NO in pulmonary tissues. PMID- 17727774 TI - [The effects of lidocaine and chronic stress on neurogenesis in the hippocampal dentate gyrus of adult mice]. AB - OBJECTIVE: To evaluate the effects of chronic stress and lidocaine administration on the neurogenesis in the hippocampal dentate gyrus of adult mice. METHODS: Twenty-four adult mice were randomly divided into 3 equal groups: control group (Group C), chronic stress group (group S) and lidocaine group (group L). The duration of the experiment was fourteen days. During the experiment, animals of group C received daily NS intraperitoneal administration; group S received daily NS intraperitoneal administration and followed by a stimulation from variable chronic stressor each day; and Group L received daily intraperitoneal lidocaine administration before being stressed. At the end of the experiment, the mice were killed and their brain were taken out. Immunohistochemistry was use to detect the expression of Brall and brain-derived neurotrophic factor (BDNP) in the hippocampal dentate gyrus. The adrenal underwent pathological examination. RESULTS: Compared with group C, a significant decrease in number of bromodeoxyuridine immunoreactive was coincident with a significant decrease in number of BDNF immunoreactive cells in the dentate gyrus of group S, but there was no significant change in Group L. Chronic stress resulted in diffuse hyperplasia of the adrenal cortex and adrenal medulla atrophy, which suggested that stress-adaption failure of adrenal gland occurred, however, it didn't bring any significant pathologic changes on the adrenal gland of the mice pretreated with lidocaine. CONCLUSION: Chronic stress results in persistent inhibition of cell proliferation of the hippocampal dentate gyrus, while lidocaine can reverse the influence by regulating the growth factors and the adrenal steroid levels. PMID- 17727776 TI - [Correlation between the prognosis of medulloblastoma and relevant clinical factors: analysis of 73 cases]. AB - OBJECTIVE: To analyze the correlation between the prognosis of medulloblastoma (MB) and relevant clinical factors. METHODS: Seventy-three MB patients, 48 males and 25 females, aged 13.6 (2 approximately 40), underwent surgical treatment and part of them underwent radiotherapy and/or chemotherapy. Follow-up was conducted among 55 cases for 40.0 months (2 months approximately 8 years and 5 months). The correlation between the prognosis and the clinical factors, such and sex, age, tumor location, extent of tumor resection, brainstem invasion, radiotherapy, chemotherapy, ventriculoperitoneal shunt and glial differentiation was analyzed. RESULTS: Six patients died postoperatively, and average survival time of the other 49 patients was 61 months. Twenty patients had a survival time of 3 years after operation, and the 3-year survival rate was 63.98%; and 8 patients survived for 5 years after operation with a 5-year survival rate of 43%. The prognosis Analysis showed that only radiotherapy was the only influencing factor of survival time. Those undergoing whole brain/posterior fossa plus spinal axis radiotherapy showed a better prognosis than those undergoing whole brain/posterior fossa radiotherapy. CONCLUSION: The prognosis of MB is not good; yet, surgical resection with regular radiotherapy and chemotherapy is helpful for the prognosis of MB. PMID- 17727775 TI - [Effects of selective head mild hypothermia on endogenous neuroprotection in brain following global cerebral ischemia/reperfusion injury: experiment with dogs]. AB - OBJECTIVE: To study the effects of selective head mild hypothermia on endogenous neuroprotection in brain following global cerebral ischemia/reperfusion. METHODS: Fifteen dogs were randomly divided into three groups: nonischemic control group (Group A, n = 4), undergoing thoracotomy without cerebral ischemia and general care for 8 hours thereafter; cerebral ischemia/reperfusion group (Group B, n = 5) undergoing thoracotomy, clipping of the ascending aorta for 18 min, cardiac resuscitation, maintenance of respiration and circulation for 8 h; and mild hypothermia group (Group C, n = 6), received selective head mild hypothermia, i.e. lowering the tympanic temperature to (34 +/- 0.5) degrees C for 8 hours after cerebral ischemia. The neurological function was assessed by Glasgow coma scale and Pittsburgh brain stem score. At the end of experiment, the dog brains were taken out to obtain the right parietal cerebral cortex. Immunohistochemistry was used to detect the parvalbumin (PV) and HSP(70). Xanthine oxidase method was used to detect the superoxide dismutase (SOD) activities: total SOD (T-SOD), manganese SOD (Mn-SOD), and copper-zinc SOD (Cu-ZnSOD). Spectrophotometry was used to detect the activities of glutathione (GSH) and glutathione peroxidase (GSH-Px). RESULTS: The comprehensive neurological score of Group C was 23.4 +/- 1.5, significantly higher than that of Group B (18.6 +/- 1.0, P < 0.05). The cerebral cortex of Group A showed a lot of PV positive neurons, the density of PV positive neurons decreased significantly in Group B (P < 0.05), and the density of PV-positive neurons win Group C was significantly higher then that of Group B, however, still significantly lower than that of Group A (both P < 0.05). The density of HSP70-LI neurons of Group A was very low (5.5 +/- 2.1), those of Groups B and C were significantly higher than that of Group A (15.6 +/- 3.7 and 27.1 +/- 4.9 respectively, P < 0.05 or P < 0.01), that of Group C being significantly higher than that of Group B (P < 0.05). The contents of GSH, T-SOD, MnSOD, Cu-ZnSOD, and GSH-Px of Group B were all significantly lower than those of Group A (P < 0.05 or P < 0.01). The contents of GSH, T-SOD, and Cu-ZnSOD of Group C were significantly higher than those of Group B (P < 0.05 or P < 0.01), CONCLUSION: Mild hypothermia may up-regulate the endogenous neuroprotection in brain tissue following cerebral ischemia/reperfusion and may be beneficial to cerebral ischemia. PMID- 17727777 TI - [Expressions of receptor-binding cancer antigen expressed on SiSo cells, vascular endothelial growth factor, and matrix metalloproteinase-9 in cervical carcinoma and correlation thereof with the invasion and metastasis of the cancerous tissues]. AB - OBJECTIVE: To investigate the expression of receptor-binding cancer antigen expressed on SiSo cells (RCAS1), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9) in early invasive cervical carcinoma and their relationship with the invasion and metastasis of the cervical cancerous tissues. METHODS: Samples of cervical tissues were obtained from 95 cases of early invasive carcinoma of cervix (ICC) and 82 cases of cervical intraepithelial neoplasm (CIN) during operation. 24 samples of normal cervical epithelium (NCE) were obtained during resection of hysteromyomas. Immunohistochemistry (S-P method) was used to detect the expression of RCAS1, VEGF, and MMP-9 in these samples. The relationship between those indexes and the factors related to clinical pathology of cervical carcinoma were analyzed statistically. RESULTS: The positive protein expression rates of RCAS1, VEGF, and MMP-9 in different samples all increased in the sequence of NCE, CIN, and ICC (0, 39.0%, and 72.6% respectively for RCAS1, 16.7%, 41.5%, and 67.4% respectively for VEGF, and 18.2%, 53.7%, and 78.9% respectively for MMP-9), with a significant difference between any 2 groups (all P < 0.001). The expression of RCAS1 protein was correlated with pelvic lymph node metastasis, intravascular and stromal infiltration, and histological grading (P = 0.001 or 0.000); but not correlated with patient's age, clinical stage, and histological types (all P > 0.05). The expression of VEGF and MMP-9 was correlated with pelvic lymph node metastasis, intravascular and stromal infiltration, and clinical stage (all P < 0.05); but not correlated with patient's age, histological grading, and histological types (all P > 0.05). There was an obviously positive correlation between the RCAS1 expression and VEGF expression (r = 0.882, P < 0.01), between the RCAS1 expression and MMP-9 expression (r = 0.868, P < 0.01), as well as between the VEGF and MMP-9 expression (r = 0.765, P < 0.01) in the cervical cancer. CONCLUSION: The positive expression of RCAS1, VEGF, and MMP-9 in invasive cervical carcinoma may play an important role in the development, lymph node metastasis, intravascular and stromal involvement of cancer cells. The expression of some metastasis related genes can be used to estimate the metastasis potentiality and is helpful for the treatment. PMID- 17727778 TI - [Hematological abnormalities in systemic lupus erythematosus and clinical significance thereof: comparative analysis of 236 cases]. AB - OBJECTIVE: To investigate the hematological abnormalities and their relationship to the disease activity of systemic lupus erythematosus (SLE). METHODS: The clinical data of 236 SLE patients, 29 males and 207 females with the age of confirmed diagnosis of 33.4, were divided into 3 groups: anemia group, with the hemoglobin (Hgb) < 100 g/L, including 2 subgroups, i.e. subgroup of anemia caused by chronic diseases (ACD) and subgroup of hemolytic anemia; low white blood cell group 1 (Group WBC1) with the WBC count < 4.0 x 10(9)/L, white blood cell group 2 (Group WBC2) with the WBC count 3.0 approximately 3.9 x 10(9)/L, immune thrombopenic purpura group (ITP group) with a platelet count < 100 x 10(9)/L, and control group without hematological changes. 72 patients underwent morphologic characterization of their bone marrow. The hematological data and the relationship thereof to the disease activity in different groups were analyzed. RESULTS: Among the 236 SLE patients 168 (71.18%) had hematological abnormalities and 68 of them (28.82%) without hematological abnormalities. 123 of the 168 patients with hematological abnormalities (52.1%) had anemia, 82 of which (66.7%) had characteristics of anemia caused by chronic diseases, 18 (14.6%) had hemolytic anemia, 8 (6.6%) had hematopoietic abnormalities, and the remaining 15 patients (12%) had anemia caused by unknown reasons. 73 of the 236 SLE patients (30.9%) had a WBC count < 4.0 x 10(9)/L and 57 patients (24.2%) had a platelet count < 100 x 10(9)/L. In the groups with hemolytic anemia, WBC count < 3.0 x 10(9)/L and thrombocytopenia, the complement levels were significant lower, and the levels of C-reactive protein (CRP) and positive anti-dsDNA antibody were significantly higher than those of the controls (all P < 0.05) The rate of positive antiphospholipid antibody of the hemolytic anemic patients and patients with thrombocytopenia were 22.2% and 15.8% respectively, both significantly higher than that of the controls (2.9%, both P < 0.05). 49 of the 72 patients undergoing morphologic characterization of bone marrow had normal cell morphology and a normal appearing bone marrow, 10 had varying degrees of pathologic hematopoietic changes, 2 lacked megakaryocytes, 9 expressed decreased proliferation in all three hematopoietic lineages, and 2 had only a decrease in erythropoiesis. CONCLUSION: The reason of the high proportion of anemia among the SLE patients in China may be the higher proportion of anemia caused by ACD in comparison with that abroad. Although SLE patients have lower rates of hemolytic anemia, HA is an important index of SLE disease activity. Thrombocytopenia and a WBC count < 3.0 x 10(9)/L are related to SLE disease activity. Abnormalities of hemopoiesis by bone marrow is one of the reasons of sever hematological changes in part of the SLE patients. PMID- 17727779 TI - [The biomechanical change of lumbar unilateral graded facetectomy and strategies of its microsurgical reconstruction: report of 23 cases]. AB - OBJECTIVE: To study the effects of unilateral graded facetectomy on lumbar stability through biomechanical analysis. The primary clinical results of unilateral facetectomy, posterior lumbar interbody fusion and unilateral pedicle screw instrumentation using X-tube system were also evaluated. METHODS: 5 functional spinal units (FSU) from fresh cadavers of 5 adults were made, divided into 5 groups to remain intact, or with the lateral 1/4, 1/2, or 3/4 or the whole of the left L4/5 articular process, and then put in the biomechanical testing apparatus to evaluate the effects of operation on the lumbar motion range of flexion, extension, lateral bending and axial rotation. Twenty-three patients, 16 males and 7 females, aged 47.7 (32 - 74), underwent unilateral facetectomy, posterior lumbar interbody fusion, and unilateral pedicle screw instrumentation using X-tube system. The clinical outcomes of the 23 patients were assessed by use of the visual analog score (VAS), Oswestry disability index (ODI), and Nakai criteria. RESULT: The experiment of the 5 FSUs showed that no significantly negative effects on the change in lumbar motion range of flexion, extension after unilateral graded facetectomy (all P > 0.05), and the stability of lateral bending and axial rotation had been greatly affected with the range of graded facetectomy exceeding 1/2 (P < 0.05). According to the Nakai criteria, the clinical effect was excellent in 15 cases (65.2%), good in 6 cases (26.1%), and fair in 2 cases (8.7%). The excellent and good cases accounted for 91.3% with a fusion rate of 95.6%. CONCLUSION: The lumbar stability is significantly affected if the range of graded facetectomy exceeds 1/2. The use of procedures of unilateral facetectomy, diskectomy, spinal nerve root decompression, autologous bone grafting, and unilateral pedicle screw fixation using X-tube is an optional strategy for minimally invasive spine technique. PMID- 17727780 TI - [Percutaneous pedicle screw fixation in thoracic-lumbar fracture using mini invasive pedicle screw system guided by navigation]. AB - OBJECTIVE: To assess the therapeutic effects of thoracic-lumbar fracture fixation with percutaneous mini-invasive pedicle screw system guided by computer navigation. METHOD: Fifty-one thoracic-lumbar fracture patients were divided into two groups: Sextant group (n = 21) undergoing percutaneous screw fixation with a minimally invasive pedicle screw system, and conventional pedicle screw fixation group (n = 30). The differences in the incision size, average blood loss during operation, surgical time, time of resuming walking after operation, numerical analogous pain score, etc. were analyzed. RESULTS: The incision length of the sextant group was 2.4 +/- 0.41 cm, significantly shorter than that of the conventional pedicle screw fixation group (17.4 +/- 3.4 cm, P < 0.001). The average blood loss during operation of the sextant group was 114 +/- 67.4 ml, significantly less than that of the conventional pedicle screw fixation group (317 +/- 113.2 ml, P < 0.001). The surgical time of the sextant group was 2.1 +/- 0.4 hr, significantly shorter than that of the conventional pedicle screw fixation group (2.7 +/- 0.7, P < 0.05). The time of resuming walking after operation of the sextant group was 2.0 +/- 0.7 d, significantly shorter than that of the conventional pedicle screw fixation group (7.2 +/- 2.5 d, P < 0.001). The postoperative NAPS was significantly lower than that before operation in both groups, however, there was no significant difference in the improvement of NAPS between the two groups. CONCLUSION: Percutaneous pedicle screw fixation using mini-invasive pedicle screw system guided by computer navigation is a good surgical therapeutic choice in thoracic-lumbar fracture. PMID- 17727781 TI - [Relationship between the biological behavior of nasal cavity or sinonasal inverted papilloma and infection of human papillomavirus]. AB - OBJECTIVE: To investigate the relationship between the prognosis of nasal inverted papilloma (NIP) and infection of human papillomavirus (HPV). METHODS: The paraffin-embedded tissue slides of 67 cases of NIP in nasal cavity or paranasal sinuses and of 10 cases of benign nasal polyps (as controls) underwent HE staining and in hybridization in situ (HIS) to detect the expression of 28 types of HPV and positive sites thereof. The 67 NIP patients, 45 males and 12 females, with the onset age of 55.7 (36 - 84), were divided into 3 groups according to the data of follow-up: non-recurrence group (n = 33, Group 1), recurrence group (n = 27, Group 2), and NIP with squamous cell carcinoma (n = 7, Group 3). RESULTS: The total HPV infection rate of the NIP slides was 49.25%, significantly higher than that of the control group (10%). The infection rates of HPV, especially the infection rates of HPV of the type 16/18, were significantly higher in Groups 2 and 3 than in Group 1. The infection rate of HPV of the type 16/18 was significantly higher in Group 3 than in other groups (all P < 0.01). The infected cells were located in the surface or upper part of the epithelial cell layer in Group 1, and in all parts of the epithelial cell layer in Group 3. CONCLUSION: the recurrence and malignant transition of NIP are related to HPV infection which may be attributed to the wider range of infected cells in these cases. The higher infection rate of high risk HPV type is one of the reasons for malignant transition. PMID- 17727782 TI - [Clinical analysis of 29 patients with clinically amyopathic dermatomyositis]. AB - OBJECTIVE: To explore the clinical features and prognosis of clinically amyopathic dermatomyositis (C-ADM). METHODS: The clinical data, including skin lesion, muscle involvement, and lung disease, of 29 patients with C-ADM, 6 males and 23 females with a male/female ratio of 1:3.83, aged 44 +/- 8, were analyzed. Skin biopsy was taken in 5 patients and lung HRCT was done in all the patients. RESULTS: The mean age at onset was (44 +/- 8) years. All patients presented with characteristic skin lesions such as Gottron's papulae (91.3%); heliotropic periorbital erythremia (75.9%); V-sign rash (37.9%); shawl-sign rash (24.1%); and periungual erythema and telangiectasias (20.7%). Gottron's papule was most commonly seen on the dorsal aspect of elbow (86.2%), proximal interphalangeal joints (58.6%), metacarpophalangeal joints (48.3%), patellae (23.8%), hip (20.7%), shoulder (13.8%), and ankle (9.5%). The cutaneous histopathologic pictures of these patients were all compatible with the skin lesions of dermatomyositis. Interstitial lung disease (ILD) was found by lung HRCT in 19 patients (65.5%). All patients received steroids combined with immunosuppressants, but rapidly progressive ILD happened to some of the patients and finally led to death due to respiratory failure in 5 of them. CONCLUSION: C ADM is most commonly seen in the middle-aged women. ILD is the commonest respiratory problem arising in C-ADM patients and can be fatal, therefore should be properly treated. PMID- 17727783 TI - [Clinical value of blink reflex:analysis of 548 patients]. AB - OBJECTIVE: To evaluate the clinic value of blink reflex (BR). METHODS: BR test was conducted among 584 patients with facial spasm (161 cases), face or upper extremities numbness (120 cases), Bell's palsy (102 cases), trigeminal neuralgia (31 cases), ptosis (30 cases), multiple cranial palsy or brain stem lesion (28 cases), cerebral vascular disease (19 cases), lateral face atrophy (16 cases), Guillain-Barre syndrome (13 cases), connective tissue disease (12 cases), diabetic peripheral neuropathy (12 cases), head trauma (11 cases), definite or suspected multiple sclerosis (10 cases), Meige syndrome (9 cases), Parkinson's disease (5 cases), or motor neuron disease (5 cases). RESULTS: 279 out of the 584 patients (47.77%) showed abnormal BR results. By analyzing of waveform, latency period and difference of bilateral side of BR test, the different BR changes caused by either peripheral damage to trigeminal nerve and facial nerve or by brain stem damages were distinguished. CONCLUSION: As one convenient test, BR helps locate the lesion of trigeminal nerve or facial nerve and has highly diagnostic value to the lesion of brain stem, even to the subclinical lesion at the early time of some disease without any symptoms. When the BR results are coordinated with those by brain stem auditory evoked potential, the abnormality of brain stem function can be found and located earlier in some situation that can result to brain stem damage such as MS and systematical disease. Coordination of BR with radionuclide study or single-fiber electromyography helps increase the differential diagnosis of spasm of eyelid and MG. PMID- 17727784 TI - [Changes of expression of cation-chloride cotransporter genes in hippocampus of cortical dysplasia: experiment with rat]. AB - OBJECTIVE: To investigate the roles of cation-chloride cotransporters-Na, K, 2Cl( ) cotransporter-1 (NKCC1) and K(+)-Cl(-) cotransporter-2 (KCC(2)) in the epileptogenesis of cortical dysplasia. METHODS: Six pregnant SD rats were given intraperitoneal injection of 1-3-bis-chloroethyl-nitrosourea (BCNU) on the embryonic day 17 (E17) and gave birth of 56 pups (experimental group) on the day P21. Five pregnant SD rats were given intraperitoneal injection of normal saline and gave birth of 48 pups (control group) on the day E21. Sixty days after birth the brains of 24 male pups in the experimental group and 22 male pups in the control group selected randomly were taken out to isolate the hippocampus. Cresyl violet staining was applied to observe the histological alterations in the hippocampus. RT-PCR was used to detect the mRNA expression of NKCC1 and KCC2. RESULTS: Cresyl-violet staining revealed heterotopic cell clusters within the hippocampus. RT-PCR showed that the ratio of NKCC1 to beta-actin of the experimental group was 0.70 +/- 0.13, significantly higher than that of the control group (0.48 +/- 0.09, P < 0.01); while the ratio of KCC2 to beta-actin of the experimental group was 0.54 +/- 0.10, significantly lower than that of the control group (0.80 +/- 0.15, P < 0.01). CONCLUSION: The upregulation of NKCC1 mRNA and the concomitant downregulation of KCC2 mRNA may be deeply related to the mechanism of epileptogenicity in cortical dysplasias. PMID- 17727785 TI - [Establishment of rat model of post-stroke depression and the effects of citalopram on behavior thereof]. AB - OBJECTIVE: To establish an animal model of post-stroke depression (PSD) and assess the effects of citalopram on PSD. METHODS: Fifty-two male SD rats were randomly divided into 3 groups. Normal group (n = 6) underwent sham operation. Chronic unpredictable mild stress (CMS) group (n = 6), underwent separate raising and CMS. Middle cerebral artery occlusion (MCAO) group (n = 24) underwent MCAO and then re-divided into 3 equal subgroups: stroke subgroup, PSD model subgroup (undergoing isolated raising and CMS so as to establish PSD models), and citalopram subgroup (treated with intraperitoneal injection of citalopram, a selective serotonin reuptake inhibitor for 6 weeks). The rats were examined dynamically at the 19th, 28th, and 42nd days after CMS by open-field test (OFT) and sucrose consumption test. RESULTS: On the 19th day after CMS the locomotor activity score of the PSD models was significantly lower (P < 0.001 compared to the baseline level of the same subgroup and to those of the control and stroke rats, P < 0.01 compared to the CMS group); and the frequency of rearing score of the PSD models was significantly decreased (P < 0.001 compared to its baseline level and to those of the control and stroke groups, and P < 0.05 compared to the CMS group). During the days 19 - 42, the frequency of locomotor and exploratory activities of the PSD model rats declined continually, from 37.8 +/- 1.7 to 34.2 +/- 1.2 and from 9.7 +/- 0.8 to 7.8 +/- 0.8 respectively, showing a tendency in just the reverse direction in the CMS group (from 41.0 +/- 1.3 to 42.3 +/- 0.8 and from 11.2 +/- 0.4 to 11.7 +/- 0.8 respectively). The PSD rats showed a reduction in sucrose preference at week 3 and afterwards (P < 0.001 compared with other groups). The levels of open-field activities and proportion of rats with sucrose preference in the citalopram subgroup were all significantly higher than those in other groups (all P < 0.001). CONCLUSION: Anhedonia and underactivity, the core symptoms in the PSD patients, can be found completely and persistently in the PSD rats. With good operability and repeatability, the PSD rat model is an ideal model for PSD research. Citalopram can improve the behavior abnormality in PSD. PMID- 17727789 TI - Synthesis of some quinoline-2(1H)-one and 1, 2, 4 - triazolo [ 4 , 3 -a ] quinoline derivatives as potent anticonvulsants. AB - PURPOSE: A new series of substituted quinoline-2(1H)-one and 1,2,4-triazolo[4,3 a]-quinoline derivatives were designed and synthesized to meet the structural requirements essential for anticonvulsant properties. METHODS: 4-substituted phenyl-3,4-dihydro-2(1H)-quinolines, 5-substituted-phenyl-4,5-dihydro-1,2,4 triazolo[4,3a]quinolines and 5-substituted-phenyl-4,5-dihydro-1,2,4-triazolo-[4,3 a]quinoline-1-(2H)-ones derivatives were synthesized using 3-substituted-phenyl-N phenyl-acrylamide as a starting material. Their anticonvulsant activity were evaluated by maximal electroshock (MES) test, subcutaneous pentylenetetrazol (scPTZ) test, and their neurotoxic effects were determined by the rotarod neurotoxicity test. RESULTS: The compounds 4-substitued-phenyl-3,4-dihydro-2(1H) quinolines (2a-f) had increased anticonvulsant effects compared to the parental compounds. The compounds 5-substituted-phenyl-4,5-dihydro-1,2,4-triazolo[4,3 a]quinolines (3a-f) had significantly increased anticonvulsant activity compared to 2a-f. However, the compounds 5-substituted-phenyl-4,5-dihydro-1,2,4 triazolo[4,3-a]quinoline-1(2H)-ones(4a-f), exhibited no anticonvulsant effects even under a high dose of 300 mg/kg. CONCLUSIONS: The triazole, but not the triazolone, modified series showed stronger anticonvulsant effects than the parent compounds. Among them, compound (3f), 5-(p-fluorophenyl)-4,5-dihydro-1,2,4 triazolo[4,3-a]quinoline, showed the strongest anticonvulsant effect with ED50 of 27.4mg/kg and 22.0mg/kg in the anti-MES and anti-PTZ test, respectively. PMID- 17727790 TI - Solubility prediction of drugs in water-cosolvent mixtures using Abraham solvation parameters. AB - PURPOSE: To provide predictive cosolvency models, the Abraham solvation parameters of solutes and the solvent coefficients were combined with the Jouyban Acree and the log-linear models. These models require two and one solubility data points to predict the solubility of drugs in water-cosolvent mixtures. Ab initio prediction methods also were employed and the results were discussed. METHOD: The Jouyban-Acree model constants were correlated with variables derived from the Abraham solvation parameters of solutes and the solvent coefficients to present quantitative structure property relationship (QSPR) models. The calculated model constants using the QSPR models were used to predict the solubility in water cosolvent mixtures. The mean percentage deviation (MPD), average absolute error (AAE) and root mean square error (RMSE) criteria were calculated to show the accuracy of the predictions. RESULTS: The overall MPD (+/-SD) of the proposed method employing solubility data in mono-solvents, i.e. two data points for each set, was 18.5+/-12.0 which indicates an acceptable prediction error from the practical point of view. The best cosolvency model employing aqueous solubility data was produced overall MPD of 75.2+/-72.6. The overall MPD of the proposed ab initio method was 74.9+/-19.3%. The models produced the same accuracy pattern considering MPD, AAE and RMSE criteria. CONCLUSION: The proposed model employing two solubility data points for each set produced acceptable prediction error (>>18%) and could be recommended for practical applications in pharmaceutical industry. MPD, AAE and RMSE criteria produced similar results considering various models. However, MPD criterion was preferred since its numerical values could be compared with experimental relative standard deviations for repeated experiments. PMID- 17727791 TI - Evaluation of skin permeation and accumulation profiles of ketorolac fatty esters. AB - PURPOSE: Classic penetration enhancement/retardation methods for improved dermal drug delivery primarily focus on co-applied chemicals aided alterations in skin accumulation/permeation profile, and in many cases, this has been achieved by compromising the systemic absorption/toxicities of penetrant/enhancer/retarder. In this study, higher dermal accumulation without systemic absorption of ketorolac and its fatty esters (esters) will be achieved by synthesizing lipophilic fatty ester soft prodrugs of ketorolac. METHODS: Ketorolac decenoate (C10:1), dodecenoate (C12:1) and palmitoleate (C16:1) were synthesized and evaluated for their lipophilicity, enzymatic hydrolysis, chemical stabilities, and skin permeation and accumulation profiles using the combination of common permeation enhancing techniques such as the use of lipophilic receptor solution, enhancer pretreatment of skins, removal of stratum corneum and delipidization of skins etc. RESULTS: Esters were highly lipophilic, chemically stable, enzymatically unstable in hairless mouse skin/liver homogenates and impermeable into the receptor solution. CONCLUSION: Higher dermal accumulation, absence of skin permeation, relative enzymatic stability in whole skins during permeation study and the pharmaceutical stability of esters could delineate a preliminary possibility for designing safer dermal agents with minimum potential for systemic absorption without the co-application of permeation enhancers or retarders. PMID- 17727792 TI - Transdermal delivery of hydrophobic and hydrophilic local anesthetics from o/w and w/o Brij 97-based microemulsions. AB - PURPOSE: To characterize the physicochemical properties of drug-loaded oil-in water (o/w) and water-in-oil (w/o) Brij 97-based microemulsions in comparison to their blank counterparts and to investigate the influence of microemulsion type on in vitro skin permeation of model hydrophobic drugs and their hydrophilic salts. METHODS: The microemulsion systems were composed of isopropyl palmitate (IPP), water and a 2:1 w/w mixture of Brij 97 and 1-butanol. The samples were characterized by visual appearance, pH, refractive index, electrical conductivity, viscosity and determination of the state of water and IPP in the formulations using differential scanning calorimetry (DSC). Transdermal flux of lidocaine, tetracaine, dibucaine and their respective hydrochloride salts through heat-separated human epidermis was investigated in vitro using modified Franz diffusion cells. RESULTS: The physicochemical properties of drug-loaded microemulsions and their blank counterparts were generally similar; however, slight changes in some physicochemical properties (apparent pH and conductivity) were observed due to the intrinsic properties of the drugs. The o/w microemulsions resulted in the highest flux of lidocaine, tetracaine and dibucaine as compared to the other formulations with in the same group of drugs. CONCLUSIONS: The characterization results showed that incorporation of the model drugs into the microemulsions did not change the microemulsion type. The permeation data exhibited that the nature of the microemulsions was a crucial parameter for transdermal drug delivery. The o/w microemulsions containing hydrophobic drugs provided the highest skin permeation enhancement. In addition, skin permeation was depended on the molecular weight of the model drugs. PMID- 17727793 TI - Cephalexin inhibits N-formylated peptide transport and intestinal hyperpermeability in Caco2 cells. AB - PURPOSE: Intestinal barrier integrity is diminished in critical illness and inflammatory bowel disease. Bacterial-derived N-formylated peptides, absorbed by the intestinal oligopeptide transporter, hPEPT1, are involved in the pathogenesis of disease-induced intestinal barrier dysfunction, via stimulation of polymorphonuclear leukocyte (PMN) migration. The purpose of this study was to determine if the hPEPT1 substrate, cephalexin, inhibits the absorption of the N formylated peptide, N-formyl-L-methionyl-L-leucyl-L-phenylalanine ("fMLP"), thereby preventing hyperpermeability in Caco2 cells. METHODS: Caco2 monolayers were grown on permeable supports. fMLP (0.1 microM) was added to apical chambers with and without cephalexin (5 and 10 mM), and fMLP effective permeability was calculated. To determine the ability of cephalexin to attenuate intestinal dysfunction, Caco2 cells were co-cultured with human PMN's in the presence of fMLP, cephalexin, and inflammatory cytokines. Monolayer integrity was assessed by measuring mannitol permeability. RESULTS: Cephalexin 10 mM significantly reduced fMLP permeability (p=0.007). Monolayer integrity (as indicated mannitol permeability) was decreased in cultures treated with inflammatory cytokines and fMLP, an effect that was attenuated by cephalexin (p<0.01). CONCLUSION: Cephalexin inhibits fMLP transport across cultured intestinal monolayers, and partially attenuates PMN-induced intestinal hyperpermeability. The use of pharmacologic hPEPT1 substrates may represent a novel means of preserving intestinal barrier integrity. PMID- 17727794 TI - Multiple oral dosing of ketoconazole increases dog exposure to ivermectin. AB - PURPOSE: The parasiticide ivermectin and the antimicrobial drug ketoconazole are macrolides that interact with P-glycoprotein. We investigated the effects of ketoconazole at a clinical dose on the pharmacokinetics of ivermectin, a CYP3A substrate with low hepatic clearance. METHODS: Beagle dogs received a single subcutaneous injection of ivermectin at 0.05 mg/kg alone (n=6) or in combination with a daily oral dose of ketoconazole 10 mg/kg over 5 days before and after ivermectin administration (n=6). The plasma kinetics of ivermectin and its metabolite were followed over 15 days by HPLC analysis. RESULTS: Co-administered ketoconazole induced a higher plasma concentration and longer residence time of ivermectin in dogs, leading to a substantial increase in the overall exposure of the animal to the drug. Ketoconazole does not interfere with the production of the ivermectin metabolite but it may rather inhibit the elimination of the parental drug by interfering with P-gp transport. CONCLUSIONS: Multiple oral dosing of ketoconazole dramatically altered the pharmacokinetics of ivermectin in dogs leading to an increase in systemic exposure to the drug. Neurotoxicity of ivermectin means that inhibition of the P-gp function at the blood-brain barrier during polytherapy using P-gp inhibitors must be taken into consideration. PMID- 17727795 TI - Lipid excipients Peceol and Gelucire 44/14 decrease P-glycoprotein mediated efflux of rhodamine 123 partially due to modifying P-glycoprotein protein expression within Caco-2 cells. AB - PURPOSE: The objective of this study was to determine the influence of two lipid excipients, Peceol(c) and Gelucire(c) 44/14 on P-glycoprotein (Pgp) activity and protein expression in human colon adenocarcinoma cells (Caco-2). Lipid excipients are increasingly used as drug delivery systems for hydrophobic drugs to increase their bioavailability by overcoming the barrier of low absorption. This study will probe a novel mechanism by which lipid excipients reduce Pgp-mediated efflux and thereby increase bioavailability of orally administered therapeutics. METHODS: Non-cytotoxic concentrations of Peceol(c) and Gelucire(c) 44/14 were determined for 24-hour treatments of Caco-2 cells using integrity of the cell membranes and mitochondrial respiration as markers. Pgp activity after treatment with non-cytotoxic concentrations of Peceol(c) and Gelucire(c) 44/14 was measured with a fluorescent Pgp substrate, rhodamine 123 (Rh123). The activity of Pgp was ascertained by measuring accumulation and the directional flux of Rh123 using the Transwell(c) semi-permeable cell culture support system. To assess the effect of Peceol(c) and Gelucire(c) 44/14 on Pgp protein expression, Western blotting with a specific Pgp antibody was performed. RESULTS. The two assays for cytotoxicity were in agreement and showed that concentrations of less than 0.5% (v/v) Peceol(c) and less than 0.02% (w/v) Gelucire(c) 44/14 were not toxic to Caco-2 cells. Rh123 accumulation was increased up to 3-fold in cells treated with sub toxic concentrations of the excipients. The flux of Rh123 across the cell monolayer was unaffected by treatment in the absorptive (apical to basolateral) direction but the efflux transport was reduced after treatment with Peceol(c), Gelucire(c) 44/14 or the positive control , 100microM verapamil. Some of the reduction in Pgp efflux activity can be explained by the reduction in protein expression after treatment with the lipid excipients; treatment with 0.25% (v/v) and 0.5% (v/v) Peceol(c) reduced Pgp protein levels to 62.4% and 68.4% of the control respectively while Gelucire(c) 44/14 treatments of 0.01% (w/v) and 0.02% (w/v) reduced Pgp to 64.5% and 51.8% respectively. CONCLUSION: In this study we utilized established methodologies to assess the inhibitory effect of the excipients on the Pgp-mediated efflux of the probe, Rh123 and tested the hypothesis that long-term treatment of Caco-2 cells with the lipid excipients, Peceol(c) and Gelucire(c) 44/14, decreased Pgp protein expression. The results suggest a new mechanism which may contribute to the improved bioavailability seen for drugs formulated with lipid-based excipients. PMID- 17727796 TI - Effect of medium pH on the cytotoxicity of hydrophilic statins. AB - PURPOSE: The aim of this study was to examine the mechanism of pravastatin- and rosuvastatin-induced cytotoxicity and the relationship between pravastatin- and rosuvastatin-induced cytotoxicity and medium pH using human prototypic embryonal rhabdomyosarcoma cell line (RD) and rat myoblast cell line (L6) as a model of in vitro skeletal muscle. METHODS: Statin-induced reduction of cell viability and apoptosis was measured by 3-(4,5-dimethylthiazol-2-yl)2,5 -diphenyl tetrazolium bromide (MTT) assay and caspase assay. Intracellular accumulation of statins was determined using an HPLC system. RESULTS: Rosuvastatin cytotoxicity, reduction of cell viability, morphological changes and caspase activation at acidic pH (pH 6.8) were significantly greater than those at neutral pH (pH 7.4). Rosuvastatin accumulation at acidic pH was greater than that at pH 7.4. On the other hand, medium pH had no effect on pravastatin accumulation. CONCLUSIONS: Rosuvastatin cytotoxicity at acidic pH is associated with increasing intracellular accumulation of rosuvastatin. On the other hand, medium pH had no effect on cytotoxicity of pravastatin. PMID- 17727797 TI - Protective effects of tungstophosphoric acid and sodium tungstate on chemically induced liver necrosis in wistar rats. AB - PURPOSE: Many chemical compounds and infectious agents such as viruses induce liver damage like necrosis or fulminant hepatic failure which is sometimes difficult to manage by medical therapies. The induced liver necrosis by carbon tetrachloride (CCl4) and thioacetamide (TAA) are exemplary models for experimental liver necrosis caused by oxygen free radicals. The aim of this study was to investigate the effects of tungstophosphoric acid (TPA) and sodium tungstate (ST) on liver injury induced by CCl4 or TAA. METHODS: Hepatoprotective effects of TPA and ST on acute liver necrosis, chemically induced, were evaluated by the activity of serum enzymes (alkaline phosphatase, alanine transaminase and aspartate transaminase), oxidative stress parameters (activity of xanthine oxidase, concentrations of malondialdehyde and production of superoxide anion), antioxidative defence markers (concentration of reduced glutathione), and histopathology in Wistar rats. Liver necrosis was induced by administering a single intraperitoneal (i.p.) injection of CCl4 (1.0 ml/kg b.wt. of 80% CCl4 in corn oil) or a single i.p. injection of TAA (400 mg/kg b.w. dissolved in normal saline). TPA and ST were administrated to rats orally for 7 weeks (50 mg/kg b.wt.) prior to induction of liver necrosis. RESULTS: Induced liver necrosis caused significant elevation of activity of liver enzymes, parameters of oxidative stress and marked changes in histopathology, like necrosis of hepatocytes, hepatocyte degeneration and infiltration of inflammatory cells. In TPA and ST pretreated rats histopathological changes were almost absent, serum enzymes and oxidative stress parameters were decreased, while at the same time the concentration of reduced gluthathione was increased. CONCLUSION: The present findings suggest that treatment with TPA and ST for 7 weeks could be useful for the prevention of hepatic injury in rats. PMID- 17727798 TI - Reversal of multidrug resistance by transferrin-conjugated liposomes co encapsulating doxorubicin and verapamil. AB - PURPOSE: Liposomes co-encapsulating doxorubicin (DOX) and verapamil (VER), and conjugated to transferrin (Tf-L-DOX/VER) were synthesized and evaluated in K562 leukemia cells. The design of this formulation was aimed at selective targeting of tumor cells, reducing cardiotoxicity of DOX and VER, as well as overcoming P glycoprotein (Pgp)-mediated multidrug resistance (MDR) phenotype. METHODS: The liposomes were prepared by polycarbonate membrane extrusion, followed by pH gradient driven remote loading and Tf conjugation. Kinetics of in vitro release of DOX and VER from liposomes was determined by measuring changes in the concentration of encapsulated drugs. Uptake of Tf-conjugated liposomes by K562 cells was evaluated by fluorescence microscopy and by fluorometry. Cytotoxicities of various formulations of DOX were determined by a 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolum bromide (MTT) assay. RESULTS: Efficiencies for liposomal loading of DOX and VER were 95% and 70%, respectively. The mean particle diameter for the liposomes was approximately 110nm. Rates of release for DOX and VER were similar in singly-loaded and co-loaded liposomes. Tf-L-DOX/VER showed efficient uptake by the TfR+ K562 cells. In DOX-resistant K562 cells (K562/DOX), Tf-L DOX/VER showed 5.2 and 2.8 times greater cytotoxicity (IC50 = 4.18 muM) than non targeted liposomes (L-DOX/VER) (IC50 = 21.7 muM) and Tf-targeted liposomes loaded with DOX alone (Tf-L-DOX) (IC50 = 11.5 muM), respectively. CONCLUSIONS: The combination of TfR targeting and co-encapsulation of DOX and VER was highly effective in overcoming drug resistance in K562 leukemia cells. PMID- 17727799 TI - Polypropylene imine dendrimer mediated solubility enhancement: effect of pH and functional groups of hydrophobes. AB - Dendrimers today are known for their three dimensional, monodispersed, highly branched, macromolecular nano-scopic architecture with number of reactive end groups. Dendrimers have been reported to act as solubilizing agents to host both hydrophilic and hydrophobic drugs. The present study was performed to investigate the effect of pH on poly(propylene) imine dendrimers (5.0G) mediated solubility enhancement of hydrophobes differing in functional groups (pKa). Weakly basic, (famotidine, -NH2 functional group; pKa 7.1), weakly acidic (indomethacin, -COOH functional group; pKa 4.5) and amphoteric (amphotericin B, -COOH and -NH2 functional groups; pKa 5.7 and 10.0) hydrophobes were selected for the study. The experiment was carried out at pH 4.0, 7.4 and 10.0. The solubility of all the drugs was enhanced at pH 7.4 and 10.0 but not at pH 4.0. The drug-dendrimer complexes followed 1:1 stoichiometry (AL type of curve) and were characterized for stability of complex, complexation efficiency and thermodynamic properties. Thermodynamic properties were utilized to elucidate the mechanism behind dendrimer mediated solubility enhancement. The data suggested that hydrophobic and electrostatic interactions were responsible for solubility enhancement. Conclusively, PPI dendrimers were found useful in solubility enhancement of not only acidic and basic but also amphoteric drugs, their solubilization ability was clearly regulated by pH and chemical nature of drug. PMID- 17727800 TI - Predicting human intestinal permeability using single-pass intestinal perfusion in rat. AB - PURPOSE: The aim of the study was the prediction of human intestinal permeability and fraction absorbed of oral dose using single-pass intestinal perfusion technique (SPIP) in rats. METHODS: Permeability coefficients in anaesthetized rats were determined for 14 compounds. Drug solution in phosphate buffered saline (PBS) was perfused through a ingle-pass intestinal perfusion (SPIP) with flow rate of 0.21 ml/min and samples were taken from outlet tubing at different time points up to 90 min. Phenol red was used as a non-absorbable marker to correct water flux through the segment. Drug concentrations in samples were determined using HPLC and permeability coefficients (Peff) were calculated. RESULTS: The examined compounds demonstrated approximately 12.5 fold difference in magnitude for rat permeability coefficients among themselves. These values were compared with published data for human intestinal permeability, and a strong correlation was found between Peff (rat) and Peff (human); (Peff (human) = 11.04 Peff (rat) - 0.0003; R2= 0.93, P<0.0001). Subsequently the fraction dose absorbed in human (Fa) was estimated and predicted after oral dosing considering Fa(human)=1-e - 38450Peff(rat) (R2= 0.91, P<0.0001). CONCLUSIONS: Considering the high correlation of rat Peff values with those of human we conclude that the SPIP could be utilized with precision to predict the human intestinal permeability. It may also be used as a reliable technique to predict the fraction of dose absorbed following oral administration of drug in solution or regular release dosage form in human. PMID- 17727801 TI - Effect of diltiazem isomers and thiamine on piglet liver microsomal peroxidation using dichlorofluorescein. AB - PURPOSE: We investigated a potential hepatoprotective role of d-cis diltiazem, l cis diltiazem, thiamine and the combination d-cis diltiazem and thiamine against lipid peroxidation in a piglet liver microsomal model. A modified in vitro dichlorofluorescein assay was developed to assess the extent of peroxidative damage induced by reactive oxygen species in the piglet liver microsomal fraction. METHODS: Microsomal membrane fraction, obtained from 3 week old female piglets, was treated with either the biologically vasoactive d-cis diltiazem or the non-vasoactive stereoisomer l-cis diltiazem (5-1000 microM) for 1 hour at 37 degrees C followed by one hour incubation with the free radical generator AAPH (2,2'-azobis-(2-amidinopropane) dihydrochloride; 1 mM) to initiate lipid peroxidation. In a separate study, piglet liver microsomes were pre-treated with d-cis diltiazem (50 or 500 microM) and thiamine (10-100 microM) to assess the antioxidant activity of the combination. RESULTS: A dose dependant inhibition of membrane lipid peroxidation was observed with d-cis diltiazem (p<0.05) but not with l-cis diltiazem, suggesting that diltiazem is stereospecific in protecting against microsomal lipid peroxidation. Combining diltiazem with thiamine further protected microsomes against lipid peroxidation compared to use of individual drugs. CONCLUSION: We conclude that diltiazem and the combination of diltiazem and thiamine offers a hepatoprotective effect against free radicals. PMID- 17727802 TI - Methods of endotoxin removal from biological preparations: a review. AB - PURPOSE: Endotoxins, also called lipopolysaccharides (LPS), are major contaminants found in commercially available proteins or biologically active substances, which often complicate study of the biological effects of the main ingredient. The presence of small amounts of endotoxin in recombinant protein preparations can cause side effects in host organism such as endotoxin shock, tissue injury, and even death. Due to these reactions, it is essential to remove endotoxins from drugs, injectables, and other biological and pharmaceutical products. An overview of this subject is provided by this article. METHODS: An extensive review of literature with regard to methods for removal of endotoxin from biotechnological preparations was carried out. RESULTS: A short history of endotoxin is presented first. This is followed by a review of chemical and physical properties of endotoxin and its pathophysiological effects when the body is exposed to LPS excessively or systemically. The techniques of endotoxin determination and interaction of endotoxin with proteins is also presented, taking into consideration the established techniques as well as the state of the art technology in this field. A review of techniques of endotoxin removal from biotechnological preparations is described, emphasizing how endotoxin removal can be carried out in an economical way based on a number of processes discussed in the literature (e.g., adsorption, two-phase partitioning, ultrafiltration and chromatography). Different methods are mentioned with relatively high protein recoveries; however, special attention is given to two-phase aqueous micellar systems, which are valuable tools for endotoxin removal from pharmaceutical proteins on a small scale because they provide a mild environment for biological materials. CONCLUSIONS: Efficient and cost-effective removal of endotoxins from pharmaceutical and biotechnology preparations is challenging. Despite development of novel methods, such as the two-phase aqueous micellar systems, in recent years, more research is needed in this field. PMID- 17727803 TI - Biosimilars: opportunity or cause for concern? AB - Biopharmaceuticals are drug products containing biotechnology-derived proteins as active substances, and have revolutionised the treatment of many diseases. A number of biopharmaceutical patents are due to expire in the next few years, or have already expired. The subsequent production of follow-on products, or 'biosimilars' has aroused interest within the pharmaceutical industry as biosimilar manufacturers strive to obtain part of an already large and rapidly growing market. The potential opportunity for price reductions versus the originator biopharmaceuticals remains to be determined, as the advantage of a slightly cheaper price may be outweighed by the hypothetical increased risk of side-effects from biosimilar molecules that are not exact copies of their originators. This review focuses on the issues surrounding biosimilars, including manufacturing, quality control, clinical efficacy and side effects, and how government and industry regulations are evolving to deal with these topics. PMID- 17727804 TI - A new concept to stimulate mucosal as well as systemic immunity by parenteral vaccination as applied to the development of a live attenuated Salmonella enterica serovar Dublin vaccine. AB - A new concept of slow "drip feeding" that enables activation of mucosal as well as systemic immunity following parenteral vaccination was demonstrated using Salmonella Dublin in a mouse model. The live vaccine candidate, N-RM25, generated from a wild S. Dublin strain utilising metabolic-drift (spontaneous chromosomal) mutations had a unique sensitivity to bile and restricted growth in the presence of a very low concentration of bile salts No. 3 (0.075% (w/v)) but also had the ability to survive in a high concentration (19.2%) of the substance. Following intraperitoneal administration with 10(7) cfu, N-RM25 colonised and survived (10(1)-10(3) cfu/g) in the liver and spleen of mice for over 24 days without causing disease. A small number of the mutant organisms also penetrated the gall bladder and gut, most likely via the enterohepatic circulation. N-RM25 induced significant levels of serum IgG, IgA and intestinal secretory IgA. A second metabolic-drift mutant (R-NM29) that was rapidly eliminated from the liver and spleen and highly unlikely to penetrate the gall bladder and gut, stimulated some systemic immunity, but induced no mucosal immunity because it did not reach the immune stimulation sites within the gut. In vaccine trials, N-RM25 was significantly more effective in eliminating the homologous challenge bacteria (S. Dublin wild strain FD436) from the internal organs and intestinal lumen when compared to R-NM29 and the negative control. N-RM25 prevented the development of systemic infection and produced 100% protection. PMID- 17727805 TI - Effects of CpG-B ODN on the protein expression profile of swine PBMC. AB - The CpG motif within bacterial DNA is a potent immuno-stimulatory moiety. Here, using a 2-D electrophoretic approach, we investigated the effect of synthetic oligodeoxynucleotide containing a B type CpG motif (CpG-B ODN) on the protein expression profile of swine peripheral blood mononuclear cells (PBMC). We found that several proteins including spondin 1, N-acetolactate alpha linked acidic dipeptidase; V kappa light chain, T cell receptor variable alpha chain, heat shock protein (Hsp) 60, Hsp70, KIAA0857 protein, and PNAS-146 were up-regulated in PBMC by CpG-B ODN stimulation. Further studies showed that CpG-B ODN-mediated Hsp60, Hsp70 and Hsp90 expressions were closely associated with the TLR9 signalling pathway. Pretreatment with inhibitors of Hsp70, Hsp90 and TLR9 all blocked the CpG-B ODN-mediated anti-apoptotic effect in swine PBMC. These results suggest that CpG-B ODN treatment of swine PBMC may enhance the expression of biologically active proteins, notably spondin 1, V kappa light chain, T cell receptor variable alpha chain and Hsps, which may play an important role in CpG-B ODN-mediated activation of immune responses and enhancement of swine PBMC survival. PMID- 17727806 TI - Bacterial lipopolysaccharide stimulates bovine neutrophil production of TNF alpha, IL-1beta, IL-12 and IFN-gamma. AB - After intramammary infection, polymorphonuclear neutrophil leukocytes (PMN) are the first cells recruited into the mammary gland. Rapid recruitment of and bacterial phagocytosis and killing by PMN are the most effective defenses against establishment of bacterial infection. In addition to their phagocytic and bactericidal properties, PMN may play a key supportive role through secretion of cytokines during the innate immune response. We sought to determine whether bovine PMN produce cytokines in response to stimulation by lipopolysaccharide (LPS). To investigate the effects of LPS on the expression of cytokines secreted by bovine PMN, we measured the expression of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-12, and interferon (IFN)-gamma by ELISA after stimulation with different concentrations of LPS, and secretion of IL-8 after co stimulation with LPS and either TNF-alpha or IL-1beta. Bovine PMN were shown to secrete TNF-alpha , IL-1beta, IL-12, IL-8 and IFN-gamma in response to LPS. Co incubation of PMN with LPS and TNF-alpha increased secretion of IL-8 when compared to LPS alone. It was concluded that LPS stimulation up-regulates the secretion of cytokines by bovine PMN, and that co-incubation of LPS with TNF alpha had an additive effect on the secretion of IL-8. These data show that bovine PMN, in addition to their phagocytic and bactericidal properties, may play a supportive role in the innate immune response to infection by Gram-negative bacteria through their ability to produce immuno-regulating cytokines. PMID- 17727807 TI - Sequence-optimised E2 constructs from BVDV-1b and BVDV-2 for DNA immunisation in cattle. AB - We report DNA immunisation experiments in cattle using plasmid constructs that encoded glycoprotein E2 from bovine viral diarrhoea virus (BVDV)-1 (E2.1) and BVDV-2 (E2.2). The coding sequences were optimised for efficient expression in mammalian cells. A modified leader peptide sequence from protein gD of BoHV1 was inserted upstream of the E2 coding sequences for efficient membrane export of the proteins. Recombinant E2 were efficiently expressed in COS7 cells and they presented the native viral epitopes as judged by differential recognition by antisera from cattle infected with BVDV-1 or BVDV-2. Inoculation of pooled plasmid DNA in young cattle elicited antibodies capable of neutralising viral strains representing the major circulating BVDV genotypes. PMID- 17727808 TI - Relationship between climate, disease severity, and causative organism for contact lens-associated microbial keratitis in Australia. AB - PURPOSE: To evaluate associations between disease severity, causative organism, and climatic variation in contact lens-related microbial keratitis in Australia. DESIGN: Prospective, observational case series. METHODS: Contact lens wearing patients (n = 236) with presumed microbial keratitis presenting to private and hospital ophthalmologists in Australia between October 1, 2003 and September 30, 2004 were identified prospectively. Clinical details, management information, and microbiology data were collected and cases were graded for severity based on lesion size and location criteria. Causative organisms were assigned to "environmental" or "endogenous" groups. Climate zone and daytime temperature and humidity were determined for the geographic location of each event. The main outcome measures were disease severity, causative organism, and climate zone. RESULTS: Severe contact lens-related microbial keratitis was more likely to occur in warmer, humid regions of the country (P < .001), compared with smaller, increasingly peripheral corneal lesions that were more common in cooler conditions (P < .001). Culture-proven keratitis was predominantly caused by environmental organisms with Pseudomonas aeruginosa being recovered most frequently. Environmental organisms were isolated more commonly from tropical regions of the country and also accounted for nearly all cases of vision loss that occurred during the study period. Humidity did not have a significant effect on causative organism. CONCLUSIONS: Climatic conditions play a role in disease severity and causative organism in contact lens-related microbial keratitis and therefore have implications for practitioners involved in contact lens care and contact lens wearers who live in or travel to the tropics. PMID- 17727809 TI - High-throughput and simultaneous measurement of homocysteine and cysteine in human plasma and urine by liquid chromatography-electrospray tandem mass spectrometry. AB - Total homocysteine (tHcy) and cysteine (tCys) concentrations in biological fluids are routinely used in the clinical diagnosis of genetic and metabolic diseases, and this necessitates the development of rapid and sensitive methods for quantification. Liquid chromatography-electrospray tandem mass spectrometry (LC MS/MS) was used to measure tHcy and tCys in 23 plasma and 21 urine samples from healthy adults and 14 urine samples from healthy children. The results were compared with a standard high-performance liquid chromatography (HPLC) method. The coefficient of variation (CV) for the LC-MS/MS method ranged from 2.9% to 6.1% for the intraassay and 4.8% to 6.4% for the interassay. Mean recoveries were close to 100% for both plasma and urinary tHcy and tCys. The mean plasma tHcy and tCys concentrations in healthy adults were 8.62 and 261.40 micromol/L, respectively. The mean urinary tHcy and tCys in adults were 0.98 and 22.60 micromol/mmol creatinine, respectively. The mean urinary tHcy and tCys in children were 1.17 and 27.43 micromol/mmol creatinine, respectively. Bland-Altman difference plots of method comparison between LC-MS/MS and HPLC showed good agreement in plasma and urinary tHcy and tCys concentrations. Our method is suitable for rapid measurements, and the reported urinary values in children will help to develop a pediatric reference range for clinical use. PMID- 17727810 TI - [Peripheral vestibular damage causes impaired navigation tasks on memorized routes in humans]. AB - OBJECTIVES: To investigate if a well-compensated unilateral peripheral vestibular hypofunction could interfere with navigation tasks on memorized routes in humans. METHODS: After a complete otoneurological investigation, fifty labyrinthine defective patients and fifty controls were invited to visually memorize three different routes (a triangle, a circle and a square) on a grey carpet and then to walk along them with eye closed clockwise and counter-clockwise (mental map navigation). The same test was then repeated with eye open (actual navigation) and again with eye closed (mental navigation). Execution time was recorded in each test. Corsi block test and a psychiatric questionnaire completed the neuropsychological examination. RESULTS: Labyrinthine-defective patients showed higher levels of anxiety and depression and performed Corsi block test with more difficulties than controls. Patients spent more time than controls in the first and third session (eye closed). No difference was recorded between clockwise and counter-clockwise navigation tasks both in patients and in controls. Patients showed a greater improvement in the third navigation task than controls. CONCLUSION: Walking on memorized routes in non-visual condition is impaired by a peripheral vestibular damage, even if patients are well compensated. This impairment could be due to a defect of the visuospatial short-term memory, as supported by Corsi block tests, but a residual sensorimotor impairment and/or an interference of psychological distress could not be definitively excluded. PMID- 17727811 TI - Effects of induced premaxillary suture fusion on the craniofacial morphology in growing rats. AB - OBJECTIVE: Due to premaxillary rapid development and fusion with the maxilla at the fetus stage, the functions of the premaxillary suture still remain unclear. This study was designed to explore the effect of artificial induced premaxillary suture fusion on craniofacial morphology. METHODS: Thirty Sprague Dawley rats were divided into control and experimental groups, with 3 week, 5 week and 8 week subgroups of five animals each. An incision was made in each rat along the premaxillary suture and cyanoacrylate was administered to immobilize the exposed premaxillary suture for experimental rats. No glue was applied to controls. Weights, dental impressions and radiographs were taken before and after surgery until sacrifice and used to determine the differences between groups using the one-way ANOVA test. RESULTS: After immobilizing the premaxillary suture, significant changes in the craniofacial morphology were measured at the different time points. In the experimental groups, local changes occurred at the 3rd week. A global alteration in craniofacial morphology was apparent at the 8th week in the experimental group compared to the control. At each successive time point, craniofacial morphological alterations increased in rats with fused premaxillary sutures. CONCLUSIONS: Induced premaxillary suture fusion can inhibit the growth of the premaxilla and cause extensive craniofacial morphological changes. These findings suggest that premaxillary suture fusion may be related to craniofacial malformation or malocclusion and to the formation of the flattened craniofacial profile in humans. PMID- 17727812 TI - Mechanisms of change in cognitive therapy for panic disorder with agoraphobia. AB - The purpose of this study was to test the predictions of an integrated cognitive and behavioral model of agoraphobic avoidance in patients with chronic panic disorder and agoraphobia during the process of observed therapeutic change. Treatment was residential with the majority (n=165, 88%) receiving cognitive therapy, while the remaining 23 (12%) received guided mastery therapy. The results of latent variable path modeling of the changes occurring over the course of this treatment suggested that the anxiety elicited by bodily sensations influenced catastrophic beliefs, which, in turn, increased avoidance. Avoidance increased the anxiety elicited by bodily sensations. PMID- 17727813 TI - Effects of preparatory information and distraction on children's cold-pressor pain outcomes: a randomized controlled trial. AB - This experimental study investigated whether preparatory sensory information was more effective in managing children's pain when coupled with a distraction technique. Seventy-eight children aged 7-12 years were randomly allocated to 1 of 4 experimental conditions. They were given either a detailed sensory description of an imminent painful event (cold-pressor arm immersion in 10 degrees C water) or control instructions lacking sensory information. During the cold-pressor task, half the sample received an imagery-based distraction intervention. Pain measures included immersion tolerance, self-reported pain intensity, and facial pain responses. Self-reported coping style was assessed using the Pain Coping Questionnaire [Reid, G. J., Gilbert, C. A., & McGrath, P. J. (1998). The pain coping questionnaire: Preliminary validation. Pain, 76, 83-96]. The effects of information provision interacted with distraction for pain intensity but not pain tolerance. Children given sensory preparation reported less intense pain when this was coupled with distraction than when it was not. Children with a distraction-based coping style showed greater tolerance when assigned to a condition congruent with their coping style. These findings suggest ways to better prepare children for painful medical procedures. PMID- 17727814 TI - A practical approach to N-glycan production by hydrazinolysis using hydrazine monohydrate. AB - Hydrazinolysis is a versatile method to liberate N-linked glycans from glycoproteins. However, the method is usually performed with anhydrous hydrazine, a highly toxic and explosive chemical used in rocket fuel. Thus despite the need to produce functionally important glyco-materials, hydrazinolysis is limited to small scale (e.g., 0.2-1 mL) reactions. In the present study, we report an alternative procedure for hydrazinolysis using hydrazine monohydrate in place of anhydrous hydrazine. The developed procedure was applied to both purified glycoproteins (Taka-amylase and transferrin) and hen egg yolk protein fraction with comparable yields to the traditional method using anhydrous hydrazine. The sialyl linkage of alpha2-6disialobiantennary oligosaccharides proved to be fully stable. The developed procedure facilitated the large-scale preparation of N linked glycans. The new method should make a substantial contribution to both small- and large-scale production of functional glycans, including therapeutically relevant human-type glycans. PMID- 17727815 TI - Thioglycoside hydrolysis catalyzed by beta-glucosidase. AB - Sweet almond beta-glucosidase (EC 3.2.1.21) has been shown to have significant thioglycohydrolase activity. While the Km values for the S- and O-glycosides are similar, the k(cat) values are about 1000-times lower for the S-glycosides. Remarkably, the pH-profile for k(cat)/Km for hydrolysis of p-nitrophenyl thioglucoside (pNPSG) shows the identical dependence on a deprotonated carboxylate (pKa 4.5) and a protonated group (pKa 6.7) as does the pH-profile for hydrolysis of the corresponding O-glycoside. Not surprisingly, in spite of the requirement for the presence of this protonated group in catalytically active beta-glucosidase, thioglucoside hydrolysis does not involve general acid catalysis. There is no solvent kinetic isotope effect on the enzyme-catalyzed hydrolysis of pNPSG. PMID- 17727816 TI - Flexibility in targeting and insertion during bacterial membrane protein biogenesis. AB - The biogenesis of Escherichia coli inner membrane proteins (IMPs) is assisted by targeting and insertion factors such as the signal recognition particle (SRP), the Sec-translocon and YidC with translocation of (large) periplasmic domains energized by SecA and the proton motive force (pmf). The use of these factors and forces is probably primarily determined by specific structural features of an IMP. To analyze these features we have engineered a set of model IMPs based on endogenous E. coli IMPs known to follow distinct targeting and insertion pathways. The modified model IMPs were analyzed for altered routing using an in vivo protease mapping approach. The data suggest a facultative use of different combinations of factors. PMID- 17727817 TI - Inhibition of p38/CREB phosphorylation and COX-2 expression by olive oil polyphenols underlies their anti-proliferative effects. AB - We investigated the anti-proliferative effects of an olive oil polyphenolic extract on human colon adenocarcinoma cells. Analysis indicated that the extract contained hydroxytyrosol, tyrosol and the various secoiridoid derivatives, including oleuropein. This extract exerted a strong inhibitory effect on cancer cell proliferation, which was linked to the induction of a G2/M phase cell cycle block. Following treatment with the extract (50 microg/ml) the number of cells in the G2/M phase increased to 51.82+/-2.69% relative to control cells (15.1+/ 2.5%). This G2/M block was mediated by the ability of olive oil polyphenols (50 microg/ml) to exert rapid inhibition of p38 (38.7+/-4.7%) and CREB (28.6+/-5.5%) phosphorylation which led to a downstream reduction in COX-2 expression (56.9+/ 9.3%). Our data suggest that olive oil polyphenols may exert chemopreventative effects in the large intestine by interacting with signalling pathways responsible for colorectal cancer development. PMID- 17727818 TI - Stimulation of ERAD of misfolded null Hong Kong alpha1-antitrypsin by Golgi alpha1,2-mannosidases. AB - Terminally misfolded or unassembled proteins are degraded by the cytoplasmic ubiquitin-proteasome pathway in a process known as ERAD (endoplasmic reticulum associated protein degradation). Overexpression of ER alpha1,2-mannosidase I and EDEMs target misfolded glycoproteins for ERAD, most likely due to trimming of N glycans. Here we demonstrate that overexpression of Golgi alpha1,2-mannosidase IA, IB, and IC also accelerates ERAD of terminally misfolded human alpha1 antitrypsin variant null (Hong Kong) (NHK), and mannose trimming from the N glycans on NHK in 293 cells. Although transfected NHK is primarily localized in the ER, some NHK also co-localizes with Golgi markers, suggesting that mannose trimming by Golgi alpha1,2-mannosidases can also contribute to NHK degradation. PMID- 17727819 TI - Downregulation of myosin II-B by siRNA alters the subcellular localization of the amyloid precursor protein and increases amyloid-beta deposition in N2a cells. AB - The Alzheimer's disease (AD) brain pathology is characterized by extracellular deposits of amyloid-beta (Abeta) peptides and intraneuronal fibrillar structures. These pathological features may be functionally linked, but the mechanism by which Abeta accumulation relates to neuronal degeneration is still poorly understood. Abeta peptides are fragments cleaved from the amyloid precursor protein (APP), a transmembrane protein ubiquitously expressed in the nervous system. Although the proteolytic processing of APP has been implicated in AD, the physiological function of APP and the subcellular site of APP cleavages remain unknown. The overall structure of the protein and its fast anterograde transport along the axon support the idea that APP functions as a vesicular receptor for cytoskeletal motor proteins. In the current study, we test the hypothesis that myosin II, important contributor to the cytoskeleton of neuronal cells, may influence the trafficking and/or the processing of APP. Our results demonstrate that downregulation of myosin II-B, the major myosin isoform in neurons, is able to increase Abeta deposition, concomitantly altering the subcellular localization of APP. These new insights might be important for the understanding of the function of APP and provide a novel conceptual framework in which to analyze its pathological role. PMID- 17727821 TI - Inhibition of human and mouse plasma membrane bound NTPDases by P2 receptor antagonists. AB - The plasma membrane bound nucleoside triphosphate diphosphohydrolase (NTPDase)-1, 2, 3 and 8 are major ectonucleotidases that modulate P2 receptor signaling by controlling nucleotides' concentrations at the cell surface. In this report, we systematically evaluated the effect of the commonly used P2 receptor antagonists reactive blue 2, suramin, NF279, NF449 and MRS2179, on recombinant human and mouse NTPDase1, 2, 3 and 8. Enzymatic reactions were performed in a Tris/calcium buffer, commonly used to evaluate NTPDase activity, and in a more physiological Ringer modified buffer. Although there were some minor variations, there were no major changes either in the enzymatic activity or in the profile of NTPDase inhibition between the two buffers. Except for MRS2179, all other antagonists significantly inhibited these ecto-ATPases; NTPDase3 being the most sensitive to inhibition and NTPDase8 the most resistant. Estimated IC(50) showed that human NTPDases were generally more sensitive to the P2 receptor antagonists tested than the corresponding mouse isoforms. NF279 and reactive blue 2 were the most potent inhibitors of NTPDases which almost completely abrogated their activity at the concentration of 100 microM. In conclusion, reactive blue 2, suramin, NF279 and NF449, at the concentrations commonly used to antagonize P2 receptors, inhibit the four major ecto-ATPases. This information may reveal useful for the interpretation of some pharmacological studies of P2 receptors. In addition, NF279 is a most potent non-selective NTPDase inhibitor. Although P2 receptor antagonists do not display a strict selectivity toward NTPDases, their IC(50) values may help to discriminate some of these enzymes. PMID- 17727822 TI - NSAIDs enhance proteasomic degradation of survivin, a mechanism of gastric epithelial cell injury and apoptosis. AB - NSAIDs cause severe gastrointestinal injury, in part by suppressing survivin, an inhibitor of apoptosis protein, both in cultured gastric epithelial cells and in human and rat gastric mucosa. The mechanism(s) of survivin down-regulation by NSAIDs is unclear. In this study, we examined whether NSAID treatment decreases survivin mRNA expression and/or enhances degradation of survivin protein via ubiquitin proteasome system in rat gastric mucosal, RGM-1 cells, and whether survivin overexpression prevents indomethacin-induced cell injury and apoptosis. Effects of indomethacin on survivin mRNA expression, survivin protein half-life and ubiquitination were examined in RGM-1 cells. Proteasome inhibitors were utilized to prevent indomethacin-induced survivin protein degradation in RGM-1 cells. The effects of stable overexpression of survivin on indomethacin-induced RGM-1 cell injury and apoptosis were examined. Results showed: (1) Indomethacin treatment did not alter survivin mRNA expression, but significantly reduced survivin protein half-life from 1.5h to approximately 1h and increased survivin ubiquitination. (2) Inhibition of ubiquitin proteasome prolonged survivin protein half-life to over 2h and inhibited indomethacin-induced survivin degradation. (3) Overexpression of survivin significantly reduced indomethacin-induced cell injury and apoptosis. In conclusion, indomethacin treatment enhances degradation of survivin via the ubiquitin proteasome machinery in RGM-1 cells, and maintenance of survivin levels is important for prevention of gastric epithelial cell injury and apoptosis. PMID- 17727820 TI - Discovery of a novel nicotinic receptor antagonist for the treatment of nicotine addiction: 1-(3-Picolinium)-12-triethylammonium-dodecane dibromide (TMPD). AB - Limitations in efficacy and high relapse rates of currently available smoking cessation agents reveal the need for more efficacious pharmacotherapies. One strategy is to develop subtype-selective nicotinic receptor (nAChR) antagonists that inhibit nicotine-evoked dopamine (DA) release, the primary neurotransmitter involved in nicotine reward. Simple alkylation of the pyridino N-atom converts nicotine from a potent agonist into a potent antagonist. The classical antagonists, hexamethonium and decamethonium, differentiate between peripheral nAChR subtypes. Using a similar approach, we interconnected varying quaternary ammonium moieties with a lipophilic linker to provide N,N'-bis-nicotinium analogs, affording a lead compound, N,N'-dodecyl-1,12-diyl-bis-3-picolinium dibromide (bPiDDB), which inhibited nicotine-evoked DA release and decreased nicotine self-administration. The current work describes a novel compound, 1-(3 picolinium)-12-triethylammonium-dodecane dibromide (TMPD), a hybrid of bPiDDB and decamethonium. TMPD completely inhibited (IC(50)=500 nM) nicotine-evoked DA release from superfused rat striatal slices, suggesting that TMPD acts as a nAChR antagonist at more than one subtype. TMPD (1 microM) inhibited the response to acetylcholine at alpha3beta4, alpha4beta4, alpha4beta2, and alpha1beta1varepsilondelta receptors expressed in Xenopus oocytes. TMPD had a 2 fold higher affinity than choline for the blood-brain barrier choline transporter, suggesting brain bioavailability. TMPD did not inhibit hyperactivity in nicotine sensitized rats, but significantly and specifically decreased nicotine self-administration. Together, the results suggest that TMPD may have the ability to reduce the rewarding effect of nicotine with minimal side effects, a pharmacological profile indicative of potential clinical utility for the treatment of tobacco dependence. PMID- 17727823 TI - Heritability of brain morphology related to schizophrenia: a large-scale automated magnetic resonance imaging segmentation study. AB - BACKGROUND: Schizophrenia is a devastating psychiatric disorder with a strong genetic component that has been related to a number of structural brain alterations. Currently available data on the heritability of these structural changes are inconsistent. METHODS: To examine heritability of morphological alterations in a large sample, we used a novel and validated fully-automated whole brain segmentation technique to study disease-related variability and heritability in anatomically defined regions of interest in 221 healthy control subjects, 169 patients with schizophrenia, and 183 unaffected siblings. RESULTS: Compared with healthy control subjects, patients showed a bilateral decrease in hippocampal and cortical gray matter volume and increases in bilateral dorsal striatum and right lateral ventricle. No significant volumetric differences were found in unaffected siblings compared with normal control subjects in any structure. Post hoc analysis of the dorsal striatum showed the volumetric increase to be widespread, including caudate, putamen, and globus pallidus. With Risch's lambda (lambda(s)), we found strong evidence for heritability of reduced cortical volume and moderate evidence for hippocampal volume, whereas abnormal striatal and ventricle volumes showed no sign of heritability. Additional exploratory analyses were performed on amygdala, thalamus, nucleus accumbens, ventral diencephalon, and cerebral and cerebellar cortex and white matter. Of these regions, patients showed increased volume in ventral diencephalon and cerebellum. CONCLUSIONS: These findings support evidence of genetic control of brain volume even in adults, particularly of hippocampal and neocortical volume and of cortical volumetric reductions being familial, but do not support measures of subcortical volumes per se as representing intermediate biologic phenotypes. PMID- 17727825 TI - Exogenous testosterone enhances responsiveness to social threat in the neural circuitry of social aggression in humans. AB - BACKGROUND: In a range of species, the androgen steroid testosterone is known to potentiate neural circuits involved in intraspecific aggression. Disorders of impulsive aggression in humans have likewise been associated with high testosterone levels, but human evidence for the link between testosterone and aggression remains correlational and inconclusive. METHODS: Twelve female participants underwent functional magnetic resonance imaging during three sessions while viewing stimuli differing in social threat value: angry and happy facial expressions. The first session served to establish associations between baseline hormone levels and neural activation. Participants were retested in a second and third session after placebo-controlled sublingual administration of .5 mg testosterone. RESULTS: Findings demonstrate consistent activation to angry versus happy faces in areas known to be involved in vertebrate reactive aggression, such as the amygdala and hypothalamus. Suprathreshold clusters were also found in the orbitofrontal cortex (Brodmann area 47), a region implicated in impulse control in humans. Baseline endocrine profiles of high testosterone and low cortisol were associated with stronger activation in subcortical structures. Neural responses in most activated regions were more persistent after testosterone administration than after placebo. CONCLUSIONS: These data demonstrate that testosterone enhances responsiveness in neural circuits of social aggression. Based on animal literature, it is argued that actions of testosterone on subcortical reactive aggression circuits give rise to this effect. Implications for our understanding of the pathophysiology of disorders of impulsive aggression are discussed. PMID- 17727824 TI - Systematic review: pharmacological and behavioral treatment for trichotillomania. AB - Trichotillomania is a psychiatric condition characterized by compulsive hair pulling. Three interventions have been studied in the treatment of trichotillomania: habit-reversal therapy (HRT) and pharmacotherapy with either selective-serotonin reuptake inhibitors (SSRI) or clomipramine. This systematic review compared the efficacy of these interventions in blinded, randomized clinical trials. The electronic databases of Medline, Premedline, PsychINFO, Embase, and the Cochrane Central Register of Controlled Trials were searched for relevant trials using the search terms "trichotillomania" or "hair pulling." Trials were eligible for inclusion if they compared habit-reversal therapy, SSRI pharmacotherapy, or clomipramine pharmacotherapy to each other or placebo and employed randomization and blinded assessment of outcome. Our primary outcome measure was mean change in trichotillomania severity. The summary statistic was standardized mean difference. Seven studies were eligible for inclusion in this review. Overall, meta-analysis demonstrated that habit-reversal therapy (effect size [ES] = -1.14, 95% confidence interval [CI] = -1.89, -.38) was superior to pharmacotherapy with clomipramine (ES = -.68, 95% CI = -1.28, -.07) or SSRI (ES = .02, 95% CI = -.32, .35). Clomipramine was more efficacious than placebo, while there was no evidence to demonstrate that SSRI are more efficacious than placebo in the treatment of trichotillomania. Future studies on trichotillomania should seek to determine if HRT can demonstrate efficacy against more rigorous control conditions that account for non-specific effects of therapy and determine if HRT can be an effective intervention for trichotillomania beyond the few sites where it is currently practiced in research studies. Future therapy and pharmacotherapy studies in trichotillomania should employ larger sample sizes and intention-to treat analysis and seek to validate clinical rating scales of trichotillomania severity. PMID- 17727826 TI - Features and a possible role of Mash1-immunoreactive cells in the dentate gyrus of the hippocampus in the adult rat. AB - Neurogenesis occurs throughout life in both the subventricular zone (SVZ) and subgranular zone (SGZ) of the dentate gyrus (DG) in the hippocampus in the adult brain. In the SVZ, it has been demonstrated that transit-amplifying neural progenitor cells, which appear between neural stem/progenitor cells (NSPCs) and neuroblasts during the neuronal differentiation process, express mammalian achaete-scute homolog 1 (Mash1), which regulates differentiation during neurogenesis. Although Mash1-positive cells (Mash1+ cells) are observed in the SGZ, the importance of Mash1 in hippocampal neurogenesis is not sufficiently understood. In the present study, using immunohistochemical techniques, we examined whether Mash1+ cells in the SGZ act as transit-amplifying neural progenitor cells, and whether chronic treadmill running can induce alterations of the Mash1+ cells in the SGZ of the DG. The present results indicated that Mash1 immunoreactivity is detected in proliferative cells, and that astrocytes or NSPCs and neuroblasts express Mash1. A quantitative analysis of Mash1-positive astrocytes or NSPCs and Mash1-positive neuroblasts indicated that approximately 90% of Mash1+ cells did not belong to astrocytic and neuronal cells. Furthermore, chronic treadmill running induced an increase in the number of proliferating Mash1+ cells. The present study suggests that the majority of the Mash1+ cells in the SGZ may be transit-amplifying neural progenitor cells. In addition, the proliferation of Mash1-positive transit-amplifying neural progenitor cells may contribute to the exercise-induced neurogenesis that is associated with the improvement of learning and memory function. PMID- 17727827 TI - Activation of microglial cells by ceruloplasmin. AB - Ceruloplasmin (Cp) is the major copper transport protein in plasma and catalyzes the conversion of toxic ferrous iron to the safer ferric iron. As an acute-phase protein, Cp is induced during inflammation. It is synthesized primarily in the liver and is expressed in several other tissues, including the brain. Elevated Cp levels have been observed in the brain of patients with neurodegenerative conditions, including Alzheimer's, Parkinson's, and Huntington's diseases. However, the exact role(s) of Cp in inflammatory and neuropathological conditions remains unclear. Microglia are the prime effector cells involved in immune and inflammatory responses in the central nervous system (CNS). They are activated during pathological conditions to restore CNS homeostasis, but chronic microglial activation endangers neuronal survival. Consequently, it is important to identify the regulators of microglial activation and the underlying mechanisms. We sought to examine whether Cp might modulate microglial activation. We observed that Cp induced nitric oxide (NO) release and inducible NO synthase mRNA expression in BV2 microglial cells and rat brain microglia. Cp also increased levels of mRNAs encoding tumor necrosis factor-alpha, interleukin-1beta, cyclooxygenase-2, and NADPH oxidase. Treatment of BV2 cells and primary microglia with Cp induced phosphorylation of p38 MAP kinase. Moreover, Cp induced nuclear factor (NF) kappaB activation, showing a more sustained pattern than seen with bacterial lipopolysaccharide. Cp-stimulated NO induction was significantly attenuated by a p38 inhibitor, SB203580, and the NF-kappaB inhibitor SN50. Cp induced secretion of TNF-alpha and prostaglandin E(2) in primary microglial cultures. These results suggest that Cp may play an important role in neuropathological conditions by stimulating various proinflammatory and neurotoxic molecules in microglia. PMID- 17727828 TI - Roles and regulation of the cardiac sodium channel Na v 1.5: recent insights from experimental studies. AB - During the past decade, Na(v)1.5, the main voltage-gated Na(+) channel in the heart, has been shown to be involved in many cardiac diseases. Genetic variants in the gene SCN5A, encoding Na(v)1.5, have been linked to various cardiac phenotypes, such as the congenital and acquired long QT syndromes, Brugada syndrome, conduction slowing, sick sinus syndrome, atrial fibrillation, and even cases of dilated cardiomyopathy. This unexpected phenotypic diversity may reflect that Na(v)1.5 is not only restricted to the initiation of the action potential and rapid cardiac conduction, but may also be involved in other, not-yet elucidated, functions. Despite the fact that our understanding of the regulation of expression, localization, and function of Na(v)1.5 is deepening, we are still far from a comprehensive view. Much of our current knowledge has been obtained by carrying out experiments using "cellular expression systems", e.g. host cells expressing exogenous Na(v)1.5. Although very informative, these techniques are limited, in that Na(v)1.5 is not expressed in the physiological cellular environment of a cardiac cell. Recently, however, there have been several studies published which used approaches closer to "normal" or pathological physiology. In an attempt to summarize recently published data, this article will review the phenotypes of genetically-modified mouse strains where Na(v)1.5 expression and activity are directly or indirectly modified, as well as the regulation of Na(v)1.5 function using native cardiac myocytes. Despite obvious limitations, the reviewed studies provide an overview of the complex multi-factorial and multi protein regulation of Na(v)1.5. PMID- 17727829 TI - Rapid and transient intracellular oxidative stress due to novel macrosphelides trigger apoptosis via Fas/caspase-8-dependent pathway in human lymphoma U937 cells. AB - The ability of the derivatives of macrosphelides (MS) core (simplified 16 membered core structure of natural MS) to induce apoptosis in human lymphoma U937 cells was investigated. Of the five compounds examined, MS core with ketones at 8 and 14 positions (MS5) showed the highest potency to induce apoptosis, while another, MS3 with one ketone, was minimal potent. MS5 was found to induce apoptosis in the U937 cells in a time- and dose-dependent fashion, as confirmed by DNA fragmentation analysis. MS5 treated cells showed increase in intracellular reactive oxygen species (ROS), glutathione depletion, Bid activation and lipid peroxidation. Pretreatment of cells with pancaspase inhibitor resulted in the complete inhibition of MS5-induced apoptosis. N-Acetyl-l-cysteine (NAC) pretreatment resulted in the increase in glutathione concentration, reduction of intracellular ROS, complete inhibition of DNA fragmentation, mitochondrial membrane potential (MMP) collapse, Fas externalization and caspase-8 activation. Furthermore, MS5-induced oxidative stress also triggered transient increase in intracellular calcium ion ([Ca2+]i) concentration which was completely inhibited by NAC. Pretreatment with an intracellular Ca2+ chelator, BAPTA-AM reduced MS5 induced DNA fragmentation and caspase-8 activation while it has marginal effects on MMP collapse. Taken together our present data showed that a rapid increase in intracellular ROS by MS5 triggers apoptosis via the Fas/caspase-8-mediated mitochondrial pathway suggesting that the presence of diketone makes the compound more potent to induce apoptosis. These characteristics of MS5 will make it useful for therapeutic applications of targeted apoptosis. PMID- 17727830 TI - Thalassemia intermedia due to homozygosity for an Asian Indian (Agammadeltabeta) degrees deletional inversion. PMID- 17727831 TI - Plasma-equivalent glucose at the point-of-care: evaluation of Roche Accu-Chek Inform and Abbott Precision PCx glucose meters. AB - BACKGROUND: Glucose testing at the bedside has become an integral part of the management strategy in diabetes and of the careful maintenance of normoglycemia in all patients in intensive care units. We evaluated two point-of-care glucometers for the determination of plasma-equivalent blood glucose. METHODS: The Precision PCx and the Accu-Chek Inform glucometers were evaluated. Imprecision and bias relative to the Vitros 950 system were determined using protocols of the Clinical Laboratory Standards Institute (CLSI). The effects of low, normal, and high hematocrit levels were investigated. Interference by maltose was also studied. RESULTS: Within-run precision for both instruments ranged from 2-5%. Total imprecision was less than 5% except for the Accu-Chek Inform at the low level (2.9 mmol/L). Both instruments correlated well with the comparison instrument and showed excellent recovery and linearity. Both systems reported at least 95% of their values within zone A of the Clarke Error Grid, and both fulfilled the CLSI quality criteria. The more stringent goals of the American Diabetes Association, however, were not reached. Both systems showed negative bias at high hematocrit levels. Maltose interfered with the glucose measurements on the Accu-Chek Inform but not on the Precision PCx. CONCLUSIONS: Both systems showed satisfactory imprecision and were reliable in reporting plasma-equivalent glucose concentrations. The most stringent performance goals were however not met. PMID- 17727832 TI - Zebrafish bmp4 functions during late gastrulation to specify ventroposterior cell fates. AB - Bone morphogenetic proteins (BMPs) are key mediators of dorsoventral patterning in vertebrates and are required for the induction of ventral fates in fish and frogs. A widely accepted model of dorsoventral patterning postulates that a morphogenetic BMP activity gradient patterns cell fates along the dorsoventral axis. Recent work in zebrafish suggests that the role of BMP signaling changes over time, with BMPs required for global dorsoventral patterning during early gastrulation and for tail patterning during late gastrulation and early somitogenesis. Key questions remain about the late phase, including which BMP ligands are required and how the functions of BMPs differ during the early and late gastrula stages. In a screen for dominant enhancers of mutations in the homeobox genes vox and vent, which function in parallel to bmp signaling, we identified an insertion mutation in bmp4. We then performed a reverse genetic screen to isolate a null allele of bmp4. We report the characterization of these two alleles and demonstrate that BMP4 is required during the later phase of BMP signaling for the specification of ventroposterior cell fates. Our results indicate that different bmp genes are essential at different stages. In addition, we present genetic evidence supporting a role for a morphogenetic BMP gradient in establishing mesodermal fates during the later phase of BMP signaling. PMID- 17727834 TI - A highly conserved Wnt-dependent TCF4 binding site within the proximal enhancer of the anti-myogenic Msx1 gene supports expression within Pax3-expressing limb bud muscle precursor cells. AB - The product of the Msx1 gene is a potent inhibitor of muscle differentiation. Msx1 is expressed in muscle precursor cells of the limb bud that also express Pax3. It is thought that Msx1 may facilitate distal migration by delaying myogenesis in these cells. Despite the role played by Msx1 in inhibiting muscle differentiation, nothing is known of the mechanisms that support the expression of the Msx1 gene within limb bud muscle precursor cells. In the present study we have used a combination of comparative genomics, mouse transgenic analysis, in situ hybridisation and immunohistochemistry to identify a highly conserved and tissue-specific regulatory sub-domain within the previously characterised Msx1 gene proximal enhancer element that supports the expression of the Msx1 gene in Pax3-expressing mouse limb pre-muscle masses. Furthermore, using a combination of in situ hybridisation, in vivo ChIP assay and transgenic explant culture analysis we provide evidence that Msx1 expression in limb bud muscle precursor cells is dependent on the canonical Wnt/TCF signalling pathway that is important in muscle shape formation. The results of these studies provide evidence of a mechanistic link between the Wnt/TCF and the Msx1/Pax3/MyoD pathways within limb bud muscle precursor cells. PMID- 17727835 TI - Pescadillo is required for Xenopus laevis eye development and neural crest migration. AB - Pescadillo is a multifunctional, nuclear protein involved in rRNA precursor processing, ribosomal assembly, and transcriptional regulation. Pescadillo has been assigned important functions in embryonic development and tumor formation. We previously identified pescadillo as a potential downstream target of non canonical Wnt-4 signaling. Here we have investigated for the first time the function of the Xenopus laevis homolog of pescadillo during early embryogenesis on a molecular level. Loss of function analysis indicates that pescadillo is required for eye development and neural crest migration. BrdU incorporation and TUNEL assays indicate that a loss of pescadillo function affects proliferation and triggers apoptosis through a p53-mediated mechanism. Furthermore, pescadillo affects the expression of early eye-specific marker genes, likely independent of its function in regulating proliferation and apoptosis, and in addition migration of cranial neural crest cells. Our data indicate that pescadillo has multiple important functions during X. laevis development and that its function is highly conserved among different species. PMID- 17727833 TI - TGF-beta mediated Msx2 expression controls occipital somites-derived caudal region of skull development. AB - Craniofacial development involves cranial neural crest (CNC) and mesoderm-derived cells. TGF-beta signaling plays a critical role in instructing CNC cells to form the craniofacial skeleton. However, it is not known how TGF-beta signaling regulates the fate of mesoderm-derived cells during craniofacial development. In this study, we show that occipital somites contribute to the caudal region of mammalian skull development. Conditional inactivation of Tgfbr2 in mesoderm derived cells results in defects of the supraoccipital bone with meningoencephalocele and discontinuity of the neural arch of the C1 vertebra. At the cellular level, loss of TGF-beta signaling causes decreased chondrocyte proliferation and premature differentiation of cartilage to bone. Expression of Msx2, a critical factor in the formation of the dorsoventral axis, is diminished in the Tgfbr2 mutant. Significantly, overexpression of Msx2 in Myf5 Cre;Tgfbr2flox/flox mice partially rescues supraoccipital bone development. These results suggest that the TGF-beta/Msx2 signaling cascade is critical for development of the caudal region of the skull. PMID- 17727836 TI - Pharmacological evidence that 5-HT(1B/1D) receptors mediate hypotension in anesthetized rats. AB - 5-Carboxamidotryptamine (5-CT; 0.003-310 microg/kg, i.v.) produced dose-dependent hypotensive responses which were blocked in a complex manner by the 5-HT(7) receptor antagonist, (R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1 piperidinyl) ethyl] pyrrolidine (SB-269970; 1 mg/kg, i.v.), in anesthetized vagosympathectomized rats. Interestingly, the 5-HT(1B/1D) receptor antagonist, N [4-methoxy-3-(4-methyl-1-piperazinyl) phenyl]-2'-methyl-4'-(5-methyl-1,2,4 oxadiazol-3-yl) [1,1-biphenyl]-4-carboxamide hydrochloride monohydrate GR-127935 (1 mg/kg, i.v.), also inhibited 5-CT-induced hypotension but the effect was clearly noncompetitive. Finally, the combination of GR-127935+SB-269970 (1 mg/kg, i.v., each) produced a further decreased of 5-CT-induced responses as compared to the effect of individual treatments. These data suggest that, in addition to 5 HT(7) receptors, 5-HT(1B/1D) receptors may also mediate hypotension in rats. PMID- 17727837 TI - Blockade of the metabotropic glutamate 2/3 receptors enhances social memory via the AMPA receptor in rats. AB - The present study examined the role of mGlu(2/3) receptors in short-term social memory using the social recognition paradigm in rats in which an adult rat is exposed to the same juvenile rat in two successive interactions. Intraperitoneal administration of the mGlu(2/3) receptor antagonist MGS0039 (0.3-3 mg/kg) or the ampakine CX546 (0.3-3 mg/kg) significantly and dose-dependently reduced the adult rat's social investigation of the same juvenile rat during the second encounter which occurred 120 min after the first encounter, indicating that both MGS0039 and CX546 enhanced social recognition. Pretreatment with the AMPA receptor antagonist NBQX (0.1-1 mg/kg, s.c.) significantly attenuated the effects of MGS0039 (3 mg/kg, i.p.) in the social recognition test. These results suggest that the mGlu(2/3) receptor blockade increases social recognition memory, presumably through stimulation of the AMPA receptor. PMID- 17727838 TI - Gatifloxacin affects GLUT1 gene expression and disturbs glucose homeostasis in vitro. AB - Gatifloxacin may induce life-threatening dysglycemia. The facilitated glucose transporter type 1 (GLUT1) protein is ubiquitously expressed in many tissues. Disturbed GLUT1 protein function weakens the systemic glycemic control and may cause dysglycemia. In this study we demonstrate that gatifloxacin modulates the transcription and reduces the expression and function of GLUT1 gene in HepG2 cells. When treated with gatifloxacin at concentrations of 3.4 mug/ml (8.4 muM) and 17 mug/ml (42 muM), GLUT1 promoter activity was stimulated by 2.8 and 3.8 folds, GLUT1 mRNA expression was decreased by 41% and 31%, and glucose uptake was decreased by 41% and 52%, respectively. Our findings imply that disturbed GLUT1 gene expression and protein function may underlie the dysglycemic effect of gatifloxacin. PMID- 17727839 TI - Effect of partial blockade of the Na(+)/Ca(2+)-exchanger on Ca(2+) handling in isolated rat ventricular myocytes. AB - SEA0400 is a selective inhibitor of the Na(+)/Ca(2+) exchanger having equal potencies to suppress both the forward and reverse mode operation of the Na(+)/Ca(2+) exchanger. Present experiments were designed to study the effect of partial blockade of Na(+)/Ca(2+) exchanger on Ca(2+) handling in isolated rat ventricular myocytes. Intracellular Ca(2+) transient and cell shortening were measured in ventricular myocytes loaded with Fura-2-AM fluorescent dye. Partial blockade of Na(+)/Ca(2+) exchanger was induced by superfusion of the cells with SEA0400 at a concentration of 0.3 microM. Amplitude of the intracellular Ca(2+) transient and cell shortening was significantly increased by SEA0400 in both field stimulated and voltage clamped myocytes, without significant elevation of diastolic Ca(2+) level and the decay time constant of the Ca(2+) transient. In patch clamped myocytes the SEA0400 induced increase in the Ca(2+) transient and cell shortening was accompanied by significant reduction of peak L-type Ca(2+) current. These effects can be explained by the autoregulative nature of cardiac Ca(2+) handling, as the reduced Ca(2+) efflux from the cell results in an increased Ca(2+) load to the sarcoplasmic reticulum leading to increased Ca(2+) release, which in turn may decrease the L-type Ca(2+) current by accelaration of Ca(2+) dependent inactivation of L-type Ca(2+) current. Our results suggest that complex changes in the Ca(2+) cycling can occur after selective pharmacological inhibition of the Na(+)/Ca(2+) exchanger. PMID- 17727840 TI - A co-culture system reveals the involvement of intercellular pathways as mediators of the lutropin receptor (LHR)-stimulated ERK1/2 phosphorylation in Leydig cells. AB - Co-cultures of lutropin receptor (LHR) positive and negative Leydig cells were used to test the hypothesis that the LHR provokes phosphorylation of the extracellular regulated kinases (ERK1/2) using intracellular and intercellular pathways. Addition of hCG to MA-10 cells (LHR positive) stimulates phosphorylation of the EGF receptor (EGFR) and ERK1/2 whereas addition of hCG to I-10 cells (LHR negative) does not. Addition of hCG to co-cultures of MA-10 and I 10 cells rapidly stimulates the phosphorylation of the EGFR and ERK1/2 in I-10 cells, however. Transfection of interfering constructs shows that the LHR mediated activation of Fyn in MA-10 cells is necessary for the phosphorylation of the EGFR and ERK1/2 in I-10 cells. This pathway can also be demonstrated in MA-10 cells but the phosphorylation of ERK1/2 in MA-10 cells also involves a second pathway mediated by protein kinase A (PKA). We propose that the LHR-mediated stimulation of the ERK1/2 cascade in Leydig cells depends on two independent pathways. One is intracellular and is mediated by PKA. The second is mediated by Fyn and it involves the release of soluble factors that act to phosphorylate the EGFR in an autocrine/paracrine fashion. PMID- 17727841 TI - A basic peptide derived from the HARP C-terminus inhibits anchorage-independent growth of DU145 prostate cancer cells. AB - Heparin affin regulatory peptide (HARP) is an 18 kDa heparin-binding protein that plays a key role in tumor growth. We showed previously that the synthetic peptide P(111-136) composed of the last 26 HARP amino acids inhibited HARP-induced mitogenesis. Here, to identify the exact molecular domain involved in HARP inhibition, we investigated the effect of the shorter basic peptide P(122-131) on DU145 cells, which express HARP and its receptor protein tyrosine phosphatase beta/zeta (RPTPbeta/zeta). P(122-131) was not cytotoxic; it dose-dependently inhibited anchorage-independent growth of DU145 cells. Binding studies using biotinylated P(122-131) indicated that this peptide interfered with HARP binding to DU145 cells. Investigation of the mechanisms involved suggested interference, under anchorage-independent conditions, of P(122-131) with a HARP autocrine loop in an RPTPbeta/zeta-dependent fashion. Thus, P(122-131) may hold potential for the treatment of disorders involving RPTPbeta/zeta. PMID- 17727842 TI - Overexpression of CRABPI in suprabasal keratinocytes enhances the proliferation of epidermal basal keratinocytes in mouse skin topically treated with all-trans retinoic acid. AB - We investigated whether ectopic expression of CRABPI, a cellular retinoic acid binding protein, influenced the actions of all-trans retinoic acid (ATRA) in transgenic (TG) mice. We targeted CRABPI to the basal vs. suprabasal layers of mouse epidermis by using the keratin 14 (K14) and keratin 10 (K10) promoters, respectively. Greater CRABPI protein levels were detected in the epidermis of adult transgenic(+) mice than in transgenic(-) mice for both transgenes. In adult mouse skin CRABPI overexpression in the basal or suprabasal keratinocytes did not cause morphological abnormalities, but did result in decreased CRABPII mRNA levels. Ectopically overexpressed CRABPI in suprabasal keratinocytes, but not in basal keratinocytes, enhanced the thickening of the epidermis induced by topical ATRA treatments (10 microM, 400 microl for 4 days) by 1.59+/-0.2-fold (p<0.05). ATRA treatment (10 microM) resulted in a 59.9+/-9.8% increase (p<0.05) in the BrdU labeling index in K10/FLAG-CRABPI TG(+) mice vs. TG(-) mice. Retinoid topical treatments reduced p27 and CYP26A1 mRNA levels in TG(+) and TG(-) mouse skin in K14 and K10/FLAG-CRABPI transgenic mice. As epidermal basal keratinocyte proliferation is stimulated by paracrine growth factors secreted by ATRA activated suprabasal keratinocytes, our results indicate that CRABPI overexpression in suprabasal keratinocytes enhances the physiological functions of ATRA. PMID- 17727843 TI - Gene deletion and pharmacological inhibition of aldose reductase protect against retinal ischemic injury. AB - Retinal ischemic injury is common in patients with diabetes, atherosclerosis, hypertension, transient ischemia attack and amaurosis fugax. Previously, signs of ischemic stress, such as pericyte loss, blood-retinal barrier breakdown and neovascularization, which can lead to occlusion of retinal vessels, have been prevented in diabetic db/db mice with aldose reductase (AR) null mutation. To determine the role in retinal ischemic injury of AR and sorbitol dehydrogenase (SDH), the first and second enzymes in the polyol pathway, mice with deletion of AR (AR(-/-)) or SDH-mutation (SDH(-/-)), or C57BL/6N mice treated with AR or SDH inhibitors were subjected to transient retinal artery occlusion (2h of occlusion and 22h of reperfusion) by the intraluminal suture method. Neuronal loss and edema observed in wildtype (AR(+/+)) retinas after transient ischemia were prevented in the retinas of AR(-/-) mice or C57BL/6N mice treated with an AR inhibitor, Fidarestat. Fewer TUNEL-positive cells and smaller accumulations of nitrotyrosine and poly(ADP-ribose) were also observed in the retinas of AR(-/-) mice. However, SDH(-/-) mice and C57BL/6N mice treated with SDH inhibitor, CP 470,711, were not protected against ischemia-induced retinal damage. Taken together, AR contributes to retinal ischemic injury through increased edema and free radical accumulation. Therefore, AR inhibition should be considered for the treatment of retinal ischemic injury often observed in diabetic patients. PMID- 17727844 TI - Integrin signaling is integral to regeneration. AB - The inability of the adult injured mammalian spinal cord to successfully regenerate is not well understood. Studies suggest that both extrinsic and intrinsic factors contribute to regeneration failure. In this review, we focus on intrinsic factors that impact regeneration, in particular integrin receptors and their downstream signaling pathways. We discuss studies that address the impact of integrins and integrin signaling pathways on growth cone guidance and motility and how lessons learned from these studies apply to spinal cord regeneration in vivo. PMID- 17727845 TI - Obstetric outcomes in donor oocyte pregnancies compared with advanced maternal age in in vitro fertilization pregnancies. AB - OBJECTIVE: To evaluate obstetric complications in women who conceived through donated oocytes compared with women who conceived through assisted reproduction using autologous oocytes. DESIGN: Retrospective cohort analysis. SETTING: Stanford Hospital and Clinics and Lucille Packard Children's hospital, both tertiary referral centers. PATIENT(S): A cohort of 71 oocyte recipients who underwent in vitro fertilization (IVF) were compared to all women over 38 years who conceived through IVF with autologous oocytes (n = 108) between January 1, 2001, and December 31, 2005, at Stanford University and subsequently delivered infants at Lucille Packard Children's Hospital. INTERVENTION(S): Assisted reproductive technology with donor oocytes. MAIN OUTCOME MEASURE(S): Obstetric charts of the donor-oocyte recipients were compared for all women over 38 years old who had conceived through IVF with autologous oocytes at the same center (n = 108) and delivered at the same hospital during the same time period. Perinatal complications including preeclampsia, diabetes, preterm labor, preterm premature rupture of membranes and placental abnormalities, mode of delivery, presentation, Apgar scores, gestational age at delivery, and weight were compared between the groups. RESULT(S): Oocyte recipients and autologous oocyte controls had similar rates of complications of prematurity, hypertensive disorders of pregnancy, gestational diabetes, and placental abnormalities. Infant birth weights and gestational age at time of delivery were similar between the two groups. CONCLUSION(S): This study suggests that women undergoing IVF with donor oocytes are not at increased risk for complications during pregnancy or at increased immediate neonatal complications compared with women of advanced maternal age undergoing IVF with autologous oocytes. PMID- 17727846 TI - Relationship of bariatric surgery to Mullerian-inhibiting substance levels. PMID- 17727847 TI - Pregnancy after laser-assisted selection of viable spermatozoa before intracytoplasmatic sperm injection in a couple with male primary cilia dyskinesia. AB - OBJECTIVE: To report an intracytoplasmatic sperm injection (ICSI) pregnancy achieved in a couple with male primary cilia dyskinesia (PCD) with viable sperm that were detected using a 1.48 microm wavelength diode laser. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 37-year-old man with infertility due to primary cilia dyskinesia; semen analysis revealed a severe oligoasthenoteratozoospermia with absence of motile spermatozoa. A 34-year-old healthy woman with a 10-year history of primary infertility. INTERVENTION(S): Selection of viable spermatozoa using the hypo-osmotic swelling (HOS) test or a 1.48 microm wavelength diode laser and subsequent ICSI. MAIN OUTCOME MEASURE(S): Sperm analysis. Fertilization and cleavage rates and pregnancy. RESULT(S): Semen samples showed no motile spermatozoa and high percentages of spermatozoa with curled flagella resembling HOS-reactive spermatozoa. To identify viable spermatozoa we used the HOS test or a 1.48 microm diode laser. The ICSI using HOS selected spermatozoa resulted in two fertilized out of four oocytes (50%), and injection of laser-selected spermatozoa resulted in four fertilized out of seven oocytes (57%). The transfer of two frozen/thawed oocytes of the laser group led to a singleton pregnancy. CONCLUSION(S): Use of a noncontact diode laser for sperm viability assessment may be a useful alternative, especially in cases where the HOS test is not informative. PMID- 17727848 TI - The influence of sperm morphology on preimplantation genetic diagnosis cycles outcome. AB - OBJECTIVE: To evaluate the impact of abnormal sperm morphology on the rates of aneuploidy, implantation, and clinical pregnancy. DESIGN: Retrospective cohort study. SETTING: University-based IVF center. PATIENT(S): Fifty-two patients undergoing their first IVF-preimplantation genetic diagnosis (PGD) cycle. INTERVENTION(S): The PGD analysis of embryos. MAIN OUTCOME MEASURE(S): Patients were divided into two groups based on sperm morphology: teratospermic group (TSG) and normal sperm group (NSG). The primary outcome measures of rates of aneuploidy, implantation, clinical pregnancy rate (PR) per cycle, and clinical PR per embryo transfer were compared between TSG and NSG according to PGD analysis results. RESULTS: A higher percentage of normal embryos was seen in the NSG (32%) versus the TSG (20%). Overall, 30% of IVF-PGD cycles had no normal embryos for transfer. The clinical PR per cycle was 44% in the NSG compared to 14% in the TSG (relative risk [RR] = 3.19; 95% confidence interval [CI] 1.1-9.0). A similar trend was noted with the clinical PR per embryo transfer with 57% patients becoming pregnant in the NSG versus 20% patients in the TSG (RR = 2.76; 95% CI 1.2-7.2). Implantation was twice as likely to occur in the NSG as compared to TSG (RR = 2.5; 95% CI 1.1-7.2). CONCLUSION(S): Rates of euploidy, implantation, clinical PR per cycle, and clinical PR per embryo transfer were higher in the NSG compared to the TSG, suggesting that sperm morphology plays an important role in the outcome of IVF-PGD cycles. PMID- 17727849 TI - Spindle imaging: a marker for embryo development and implantation. AB - OBJECTIVE: To examine whether the presence of birefringent spindles in living human oocytes can be used as a predictive factor associated with embryo morphology to allow embryo selection before transfer and its association with IVF outcomes. DESIGN: Prospective study. SETTING: Assisted reproduction center in Brazil. PATIENT(S): One hundred fifty-seven patients undergoing intracytoplasmic sperm injection cycles, resulting in 1,097 metaphase II oocytes. INTERVENTION(S): Meiotic spindles were evaluated before intracytoplasmic sperm injection in all metaphase II oocytes. MAIN OUTCOME MEASURE(S): Meiotic spindles' imaging and fertilization rate, embryo development, and implantation rate. RESULT(S): Birefringent spindles were detected in 65.9% (SD group). The normal fertilization rate and rate of early-cleavaged embryos were higher in the SD group compared with in the spindle-non-detected (SND) group. When only embryos from the SD group were selected for transfer, the pregnancy and implantation rates were 44.4% and 23.0%, and when only embryos from the SND group were transferred, those rates were 18.2% and 8.7%, respectively (statistically significant differences). CONCLUSION(S): Spindle visualization can be an important tool for predicting better fertilization potential, embryo development, and clinical outcomes, suggesting that embryo selection for transfer may be based not only on embryo morphology but also on oocyte nuclear maturity. PMID- 17727850 TI - Prolonged stimulation with tumor necrosis factor-alpha induced partial methylation at PR-B promoter in immortalized epithelial-like endometriotic cells. AB - The promoter of P receptor isoform B (PR-B) has recently been shown to be hypermethylated in endometriotic tissues, but one question remains as what causes the aberrant methylation. We show that sustained stimulation of an epithelial like endometriotic cell line with tumor necrosis factor alpha stimulation for 30 days induced partial methylation in the promoter region of PR-B with concomitant reduction of PR-B expression. PMID- 17727851 TI - Cortisol determination in hair and faeces from domestic cats and dogs. AB - The present study explored the feasibility of a hair cortisol assay in domestic cats (Felis silvestris catus) and dogs (Canis familiaris) as a valid and reliable alternative to existing non-invasive techniques for monitoring the hypothalamic pituitary-adrenal (HPA) axis activity. To this aim, 56 new hair growth samples and 870 faecal samples from 27 domestic cats and 29 domestic dogs were collected and cortisol content was assessed. A significant positive association was observed in both species between the concentrations of cortisol determined in hair and faeces. This finding is discussed in the light of the existing knowledge of hair physiology and in the perspective of its application to studies on chronic stress. PMID- 17727852 TI - Local anesthesia: an appropriate technology for simple fistula repair. AB - OBJECTIVES: To assess the efficacy of local infiltrative anesthesia with lidocaine hydrochloride in patients undergoing the surgical repair of a simple vesico-vaginal fistula. METHODS: The study was carried out with 21 patients undergoing the repair of a simple midvaginal vesico-vaginal fistula. The patients' perception of pain was evaluated intraoperatively. RESULTS: Most patients indicated that the anesthetic agent provided adequate analgesia, and all fistulas were repaired successfully without postoperative complications. CONCLUSION: Repairing simple vesico-vaginal fistulas is feasible with a local infiltrative anesthetic. PMID- 17727853 TI - Obstetric vesico-vaginal fistulas at the National Hospital of Niamey, Niger. AB - OBJECTIVE: To determine the epidemiologic and therapeutic characteristics of obstetric vesico-vaginal fistulas at the National Hospital of Niamey, Niger. METHODS: From December 2003 to February 2005, 111 consecutive patients with vesico-vaginal fistulas presenting for treatment were included and prospectively followed up. Demographic and clinical data were collected. The patients were re evaluated 3 months after surgery. RESULTS: Among the 104 patients treated surgically 87% were aged between 15 and 36 years; 84% were married before they were 19 years old; 51% were divorced; and 80% did not live with their husbands. The fistula was caused by the first delivery in 43% of the patients; 93% were in labor for more than 24 hours; 35% were delivered at home; and perinatal death was 100%. The overall cure rate was 73%. CONCLUSION: These epidemiologic characteristics provide data towards the development of an obstetric fistula prevention program in Niger. PMID- 17727854 TI - Social and economic consequences of obstetric fistula: life changed forever? AB - OBJECTIVES: To summarize the social, economic, emotional, and psychological consequences incurred by women with obstetric fistula; present the results of a meta-analysis for 2 major consequences, divorce/separation and perinatal loss; and report on improvements in health and self-esteem and on the possibility of social reintegration following successful fistula repair. METHODS: We conducted a review of the literature published between 1985 and 2005 on fistula in developing countries. We then performed a meta-analysis for 2 of the major consequences of having a fistula, divorce/separation and perinatal child loss. RESULTS: Studies suggest that surgical treatment usually closes the fistula and improves the physical and mental health of affected women. CONCLUSION: With additional social support and counseling, women may be able to successfully reintegrate socially following fistula repair. PMID- 17727855 TI - Where should obstetric vesico-vaginal fistulas be repaired: at the district general hospital or a specialized fistula center? AB - Expanded surgical capacities are required to treat obstetric fistulas. Achieving a balance between relative ease of access to services and use of the appropriate clinical setting is difficult. This article asks, "Are obstetric fistulas best repaired locally, at the district hospital where more women would have greater access, or is it necessary to provide these services at a tertiary referral or fistula center, where specialized surgical procedures can be conducted? Each possibility has advantages and disadvantages. The author concludes that 3 critical factors are necessary to provide safe and effective fistula repair services: adequate, long-term funding to cover the costs of all aspects of the care; the presence of a surgeon who is a "fistula champion"; and adequate operating theatre time and supplies. Without external funding, these prerequisites are almost impossible to meet at rural district hospitals. PMID- 17727856 TI - Sentinel lymph node mapping in gynecologic malignancies. AB - Lymph node status is the most important prognostic factor for women with vulvar, cervical and endometrial carcinoma and complete lymph node dissection has historically been an integral part of the surgical treatment of these diseases. Lymphadenectomy can be morbid for patients, who may experience wound breakdown, lymphocyst formation or chronic lymphedema, among other problems. Sentinel lymph node mapping is a newer technology that allows selective removal of the first node draining a tumor thereby allowing a potentially less aggressive procedure to be performed. Sentinel node mapping is well accepted for the management of breast carcinoma and cutaneous melanoma, and has resulted in reduced morbidity without adversely affecting survival. Sentinel node mapping is currently being investigated for treatment of gynecologic cancers. Recent studies show promise for incorporating the sentinel node mapping technique for treatment of several gynecologic malignancies. PMID- 17727857 TI - Microsatellite analysis reveals marked genetic differentiation between Haemonchus contortus laboratory isolates and provides a rapid system of genetic fingerprinting. AB - Many of the Haemonchus contortus isolates currently used for experimental work were originally derived from different regions of the world and are commonly exchanged between laboratories. In most cases, these are largely genetically uncharacterised other than the analyses conducted on specific genes of interest. We have used a panel of eight microsatellite markers to genetically characterise five different commonly used H. contortus isolates including MHco3 (ISE), the isolate chosen for full genome sequencing as part of the H. contortus genome project. There is an extremely high level of genetic differentiation between each of the isolates except the two which have a common origin, MHco1 (MOSI) and MHco3 (ISE). We have investigated the amplification of microsatellite markers from pooled DNA as a potential method for fingerprinting different isolates. Good estimates of the true allele frequencies can be made by amplification from either pooled adult DNA or bulk L3 DNA for seven out of the eight markers tested. Both single worm genotyping and bulk DNA fingerprinting revealed no genetic differentiation between adult worms in the host and larvae derived from faecal culture. Furthermore, none of the eight markers showed genetic changes when isolates were passaged through different individual hosts. Hence the microsatellite genotyping of bulk larval DNA samples provides a simple and rapid method to genetically define and monitor laboratory isolates, and to determine their relationship with particular field populations. PMID- 17727858 TI - Progression of calcified coronary atherosclerosis: relationship to coronary risk factors and carotid intima-media thickness. AB - BACKGROUND: The determinants of coronary artery calcium (CAC) progression are not well understood. Prior studies have shown a limited relationship between CAC progression and traditional coronary risk factors. We hypothesized that the extent of non-calcified atherosclerosis detected using carotid intima-media thickness (CIMT) would predict progression of calcified atherosclerosis. METHODS: One hundred and eighty healthy male participants (mean age 47.9) with CAC from the Prospective Army Coronary Calcium (PACC) project volunteered to undergo a second EBCT scan, risk factor assessment, lab testing, and CIMT assessment 4.2+/ 1.3 years after their original scan. All results were independently examined, blinded to baseline data. A change in CAC score >or=15% per year was defined as clinically significant progression. RESULTS: CAC progression occurred in 60.2%. Compared to participants without progression, those with progression had higher triglycerides, LDL and total cholesterol and Framingham risk scores, but similar blood pressure, HDL cholesterol, blood glucose, C-reactive protein, fibrinogen, and body mass index. CIMT was significantly higher among those with versus without CAC progression (0.660 mm versus 0.603 mm; P=0.001). Each quintile of increasing CIMT was independently associated with a 35% increase in the odds of CAC progression (P=0.01), after controlling for the Framingham risk score and C reactive protein. CONCLUSION: Among middle-aged men with coronary calcium, increasing extent of non-calcified atherosclerosis is strongly associated with coronary artery calcium progression over 4 years. PMID- 17727859 TI - Relationship between degree of remodeling and CT attenuation of plaque in coronary atherosclerotic lesions: an in-vivo analysis by multi-detector computed tomography. AB - Multi-detector CT (MDCT) permits non-invasive visualization of the coronary arteries. Coronary plaque can be visualized, and earlier studies have indicated that the CT attenuation measured in atherosclerotic plaques is influenced by plaque composition. Also, MDCT has been shown to permit assessment of remodeling of coronary atherosclerotic lesions. It is assumed that both lipid-rich plaques and those that display positive remodeling are more prone to rupture and erosion. We thus evaluated the relationship between remodeling and CT attenuation of coronary atherosclerotic plaque by MDCT. METHODS: Seventy-six patients were investigated by contrast-enhanced 64-slice CT. One-hundred twelve atherosclerotic lesions without substantial calcification and visualized with high image quality were selected. Multiplanar reconstructions orthogonal to the coronary artery were rendered at the lesion and the proximal reference site. Cross-sectional vessel areas were measured to determine the remodeling index (RI: lesion vessel area/reference vessel area) and the CT attenuation of plaque was measured by fitting a region of interest to the plaque area. CT attenuation of plaque was correlated to the presence of positive remodeling index (RI>1.05). RESULTS: The mean cross-sectional vessel area in the lesion was 0.25+/-0.08 cm(2), the mean reference vessel area was 0.22+/-0.09 cm(2). The mean CT attenuation of the atherosclerotic plaque in the lesions was 71+/-26 HU. CT attenuation of plaque was significantly lower in 72 lesions that displayed positive remodeling (59+/-22 HU) than in 40 lesions with no or with negative remodeling (91+/-20 HU, p<0.001). CONCLUSIONS: Positive remodeling of coronary atherosclerotic lesions correlates to lower CT attenuation of plaque, which has been demonstrated to be associated with lipid-rich plaque. Both characteristics indicate increased risk for plaque rupture and subsequent events and could thus prove useful when the use of CT imaging for the detection of "vulnerable plaque" is considered. PMID- 17727860 TI - A dose-titration and comparative study of rosuvastatin and atorvastatin in patients with homozygous familial hypercholesterolaemia. AB - This study assessed the efficacy of rosuvastatin for reducing plasma low-density lipoprotein (LDL) cholesterol after 18 weeks of open-label, forced titration in patients with homozygous familial hypercholesterolaemia (hoFH) and compared the efficacy of rosuvastatin 80 mg and atorvastatin 80 mg. Forty-four patients aged 8 63 years (body mass >or=32 kg) entered the study; 4 had portacaval shunts and 11 were receiving plasmapheresis. Patients sequentially received rosuvastatin 20, 40 and 80 mg/day for 6 weeks. Patients remaining in the trial after 18 weeks received double-blind, randomised crossover treatment with rosuvastatin 80 mg/day and atorvastatin 80 mg/day for 6 weeks each. After 18 weeks, mean (S.D.)% reduction from baseline in LDL cholesterol was 22 (21)% overall and by 26 (15)% in 29 patients who neither had a portacaval shunt nor were receiving plasmapheresis. Seventy-two percent of the patients had >or=15% reductions in LDL cholesterol and were considered responders and included patients who had portacaval shunts or were receiving plasmapheresis. Mean LDL reductions from baseline after crossover treatment (n=21) with rosuvastatin 80 mg and atorvastatin 80 mg were 19 and 18%, respectively. All treatments were well tolerated. Rosuvastatin may have therapeutic value in the management of hoFH. PMID- 17727861 TI - Hepatic cell-specific ATP-binding cassette (ABC) transporter profiling identifies putative novel candidates for lipid homeostasis in mice. AB - BACKGROUND: ABC-transporters play an important role in lipid trafficking. Therefore, hepatic expression patterns of ABC-transporters involved in the regulation of cholesterol metabolism were evaluated. METHODS AND RESULTS: RT-PCR analysis showed that the mRNA expression of 38 ABC-transporters detected in livers of C57Bl/6 mice varied greatly. Although most ABC-transporters were ubiquitously expressed, some members displayed very restricted expression patterns, e.g. ABCA6, A8, B1, B8, B10, B11, C3, D2, and G5/G8 were exclusively (>99%) expressed in parenchymal cells. Interestingly, another 13 ABC transporters, including ABCA4, A5, A9, A13, B2, B9, C1, C5, D3, D4, F2, G1, and G4 were primarily expressed in Kupffer cells. Although Kupffer cells only contribute to 2.5% of the total liver protein, these 13 genes did contain 9-27% of the total liver expression. Western-type diet feeding (0.25% cholesterol, 15% fat) induced the expression of several primarily Kupffer cell expressed genes, including ABCA5, B9, D3, and D4 (2 to 3-fold higher), whereas the other ABC transporters were not significantly changed. CONCLUSIONS: Our findings underscore the importance of cellular localization for studying the regulation of key ABC transporters in liver cholesterol homeostasis. Furthermore, several novel ABC transporters, including ABCA5, B9, D3, and D4 were identified as putative novel candidates involved in liver macrophage cholesterol homeostasis. PMID- 17727862 TI - Frictional contact mechanics methods for soft materials: application to tracking breast cancers. AB - Mammography is currently the most widely used screening and diagnostic tool for breast cancer. Because X-ray images are 2D projections of a 3D object, it is not trivial to localise features identified in mammogram pairs within the breast volume. Furthermore, mammograms represent highly deformed configurations of the breast under compression, thus the tumour localisation process relies on the clinician's experience. Biomechanical models of the breast undergoing mammographic compressions have been developed to overcome this limitation. In this study, we present the development of a modelling framework that implements Coulomb's frictional law with a finite element analysis using a C(1)-continuous Hermite mesh. We compared two methods of this contact mechanics implementation: the penalty method, and the augmented Lagrangian method, the latter of which is more accurate but computationally more expensive compared to the former. Simulation results were compared with experimental data from a soft silicon gel phantom in order to evaluate the modelling accuracy of each method. Both methods resulted in surface-deformation root-mean-square errors of less than 2mm, whilst the maximum internal marker prediction error was less than 3mm when simulating two mammographic-like compressions. Simulation results were confirmed using the augmented Lagrangian method, which provided similar accuracy. We conclude that contact mechanics on soft elastic materials using the penalty method with an appropriate choice of the penalty parameters provides sufficient accuracy (with contact constraints suitably enforced), and may thus be useful for tracking breast tumours between clinical images. PMID- 17727863 TI - Pressure-adjusted continual flow heart-cutting for the high throughput determination of amphetamine-type stimulant drugs in whole blood by fast multidimensional gas chromatography-mass spectrometry. AB - Innovative features and technical improvements in modern bench-top quadrupole gas chromatograph-mass spectrometer (GC-MS) have prepared the way for faster and more cost-effective applications while still maintaining sufficient chromatographic resolution, speed of MS data acquisition and reliability of analytical methodology. In this paper, a short wide-bore capillary column with low film thickness (5 m x 0.32 mm i.d., 0.1 microm) was used a pre-fractionating column and only chosen heart-cuts were transferred to the second chromatographic dimension (15 m x 0.25 mm i.d., 0.25 microm) by means of a pressure-adjusted continual flow type switching device for quantification of five common amphetamine-type stimulant drugs. The instrumental setting used, in combination with carefully optimized operational fast GC and MS parameters, markedly decreased the retention times of the targeted analytes, e.g., amphetamine 0.891 min and methamphetamine 1.037 min, and the total chromatographic runtime (1.700 min), as well as reducing the need for continuous cleaning of the MS ion source and increasing column life compared with conventional GC-MS approaches. The performance of the instrumental configuration and analytical method was evaluated in validation experiments and the method was also applied to authentic samples. The method demonstrates the potential of fast GC-MS in combination with a gas phase microfluidic Deans switch device for analysing of (semi)volatile compounds, such as amphetamine-type stimulant (ATS) drugs. This should be particularly useful in modern laboratories aiming at cost-efficient analysis as well as the optimum use of available laboratory capacity and instrumentation. PMID- 17727864 TI - Classification of weathered petroleum oils by multi-way analysis of gas chromatography-mass spectrometry data using PARAFAC2 parallel factor analysis. AB - The application of multi-way parallel factor analysis (PARAFAC2) is described for the classification of different kinds of petroleum oils using GC-MS. Oils were subjected to controlled weathering for 2, 7 and 15 days and PARAFAC2 was applied to the three-way GC-MS data set (MSxGCxsample). The classification patterns visualized in scores plots and it was shown that fitting multi-way PARAFAC2 model to the natural three-way structure of GC-MS data can lead to the successful classification of weathered oils. The shift of chromatographic peaks was tackled using the specific structure of the PARAFAC2 model. A new preprocessing of spectra followed by a novel use of analysis of variance (ANOVA)-least significant difference (LSD) variable selection method were proposed as a supervised pattern recognition tool to improve classification among the highly similar diesel oils. This lead to the identification of diagnostic compounds in the studied diesel oil samples. PMID- 17727865 TI - Extraction and analysis of intact glucosinolates--a validated pressurized liquid extraction/liquid chromatography-mass spectrometry protocol for Isatis tinctoria, and qualitative analysis of other cruciferous plants. AB - Glucosinolates have attracted significant interest due to the chemopreventive properties of some of their transformation products. Numerous protocols for the extraction and analysis of glucosinolates have been published, but limited effort has been devoted to optimize and validate crucial extraction parameters and sample preparation steps. We carried out a systematic optimization and validation of a quantitative assay for the direct analysis of intact glucosinolates in Isatis tinctoria leaves (woad, Brassicaceae). Various parameters such as solvent composition, particle size, temperature, and number of required extraction steps were optimized using pressurized liquid extraction (PLE). We observed thermal degradation of glucosinolates at temperatures above 50 degrees C, and loss of >60% within 10min at 100 degrees C, but no enzymatic degradation in the leaf samples at ambient temperature. Excellent peak shape and resolution was obtained by reversed-phase chromatography on a Phenomenex Aqua column using 10mM ammonium formate as ion-pair reagent. Detection was carried out by electrospray ionisation mass spectrometry in the negative ion mode. Analysis of cruciferous vegetables and spices such as broccoli (Brassica oleracea L. var. italica), garden cress (Lepidium sativum L.) and black mustard (Sinapis nigra L.) demonstrated the general applicability of the method. PMID- 17727866 TI - Quantification and screening of pesticide residues in food by gas chromatography exact mass time-of-flight mass spectrometry. AB - A gas chromatography-exact mass time-of-flight mass spectrometry (GC-TOF-MS) method has been developed for the quantification of approximately one hundred pesticides in baby food, pear and lettuce samples. Prior to analysis, co extractives were removed from acetonitrile:toluene (80:20) extracts using dispersive solid-phase extraction with primary secondary amine (50mg) and carbon sorbent (50mg). The concentration of pesticides in the extracts was measured using an extracted mass chromatogram window of 0.05 Th. Samples spiked with pesticides at 0.01 and 0.1 mgkg(-1) yielded average recoveries in the range of 70 109% with relative standard deviations less than 26% and displayed good linearity for the majority of the analytes. The method was applied to the screening of pear and lettuce samples for pesticide residues. Targeted quantification and exact mass peak detection, deconvolution and library searching packages were used successfully to detect and identify incurred residues present in the samples at concentrations above 0.01 mgkg(-1). The new feature dynamic range enhancement, improved mass accuracy, and hence detection and quantification of the analytes across the concentration range studied. PMID- 17727867 TI - Enantioselective separation of all-E-astaxanthin and its determination in microbial sources. AB - A method for the enantioselective separation of all-E-astaxanthin (3,3'-dihydroxy beta,beta-carotene-4,4'-dione), an important colorant in the feed industry, was developed. Different chiral stationary phases (CSPs) such as Pirkle phases (R,R Ulmo and l-leucine), modified polysaccharides and a beta-cyclodextrin have been investigated on their separation performance of astaxanthin enantiomers. Direct resolution was only achieved employing the Chiralcel OD-RH (cellulose-tris-3,5 dimethylphenyl-carbamate) under reversed phase conditions. The chiral separation of the enantiomeric forms of astaxanthin produced in microalgae and yeasts was reported. The yeast Xanthophyllomyces sp. produces astaxanthin predominantly in the R,R configuration, whereas in the green microalgae Scenedesmus sp. astaxanthin is built primarily in the S,S form. The separation method for the identification of astaxanthin enantiomers is of great interest since astaxanthin is used as functional food additive in human nutrition. Moreover the method may be used as a food chain indicator in farmed salmon. PMID- 17727868 TI - Multiple headspace solid-phase microextraction for eliminating matrix effect in the simultaneous determination of haloanisoles and volatile phenols in wines. AB - This paper proposes a multiple headspace solid-phase microextraction (MHS-SPME) method coupled to gas chromatography-tandem mass spectrometry detection (GC/MS/MS) for the simultaneous determination of 2,4,6-trichloroanisole, 2,3,4,6 tetrachloroanisole, pentachloroanisole, 2,4,6-tribromoanisole, 4-ethylphenol, 4 ethylguaiacol, 4-vinylphenol and 4-vinylguaiacol in wines. These compounds are involved in the presence of "cork taint" and Brett character in wines. The MHS SPME method is a modification of SPME developed for quantitative analysis that avoids possible matrix effects based on an exhaustive analyte extraction from the sample. After demonstrating the existence of matrix effect in the analysis of the target compounds by HS-SPME with a divinylbenzene/Carboxen/polydimethylsiloxane (DVB/CAR/PDMS) fibre, the MHS-SPME method was developed and validated. The proposed method showed satisfactory linearity, precision and detection limits, all below the odour detection thresholds of the compounds in wine matrices. Good recoveries were observed for all compounds, always above 90%, and the repeatability obtained was considered acceptable, ranging between 2 and 11%. After checking the applicability of the method by comparing the results recorded with those obtained with the standard addition method, the method was applied successfully to the analysis of wine samples. To our knowledge, this is the first time that MHS-SPME combined with GC/MS/MS has been applied to simultaneously determine haloanisoles and volatile phenols in wine. PMID- 17727869 TI - Multiresidue analysis of acidic and polar organic contaminants in water samples by stir-bar sorptive extraction-liquid desorption-gas chromatography-mass spectrometry. AB - The feasibility of stir-bar sorptive extraction (SBSE) followed by liquid desorption in combination with large volume injection (LVI)-in port silylation and gas chromatography-mass spectrometry (GC-MS) for the simultaneous determination of a broad range of 46 acidic and polar organic pollutants in water samples has been evaluated. The target analytes included phenols (nitrophenols, chlorophenols, bromophenols and alkylphenols), acidic herbicides (phenoxy acids and dicamba) and several pharmaceuticals. Experimental variables affecting derivatisation yield and peak shape as a function of different experimental PTV parameters [initial injection time, pressure and temperature and the ratio solvent volume/N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide (MTBSTFA) volume] were first optimised by an experimental design approach. Subsequently, SBSE conditions, such as pH, ionic strength, agitation speed and extraction time were investigated. After optimisation, the method failed only for the extraction of most polar phenols and some pharmaceuticals, being suitable for the determination of 37 (out of 46) pollutants, with detection limits for these analytes ranging between 1 and 800 ng/L and being lower than 25 ng/L in most cases. Finally, the developed method was validated and applied to the determination of target analytes in various aqueous environmental matrices, including ground, river and wastewater. Acceptable accuracy (70-130%) and precision values (<20%) were obtained for most analytes independently of the matrix, with the exception of some alkylphenols, where an isotopically labelled internal standard would be required in order to correct for matrix effects. Among the drawbacks of the method, carryover was identified as the main problem even though the Twisters were cleaned repeatedly. PMID- 17727871 TI - A simple method for the preparation of activated carbon fibers coated with graphite nanofibers. AB - A simple method is described for the preparation of activated carbon fibers (ACFs) coated with graphite nanofibers (GNFs). Low-pressure-plasma mixed-gas (Ar/O2) treatment of the ACFs led to the growth of GNFs on their surface. The growth was greater at higher power inputs, and from TEM observations the GNFs were seen to be of herringbone type. It was found that the N2 adsorption capacity of the ACFs did not sharply decrease, and that volume resistivity of the ACFs enhanced as a result of this treatment. PMID- 17727870 TI - Copper acetylacetonate anchored onto amine-functionalised clays. AB - Copper (II) acetylacetonate was immobilised directly onto two clays, laponite (Lap) and K10-montmorillonite (K10), and after their amine functionalisation with (3-aminopropyl)triethoxysilane (APTES). All the materials were characterised by nitrogen adsorption isotherms at -196 degrees C, elemental analysis, TG-DSC, XRD, and IR spectroscopy. The K10-based materials were also characterised by XPS. The APTES-functionalised K10 showed higher copper loading than K10, indicating that the clay functionalisation enhanced the complex immobilisation; on the contrary, in Lap-based materials higher metal content was obtained by direct complex anchoring, probably due to the delaminated nature of Lap which induced the particles aggregation on functionalisation with APTES. All the results pointed out that the Cu complex was anchored onto the amine-functionalised clays by Schiff condensation between the amine groups of anchored APTES and the carbonyl groups of the acetylacetonate ligand, whereas direct immobilisation proceeded mostly through interaction between the metal centre and the clay surface hydroxyl groups. PMID- 17727872 TI - One-step synthesis of gold nanoparticles using azacryptand and their applications in SERS and catalysis. AB - A new aqueous-phase method for the preparation of stable gold nanoparticles by using 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosane (azacryptand) as both reductant and stabilizer is reported. Reduction of HAuCl(4) with azacryptand at room temperature yields nano-sized particles within a short time. The obtained gold nanoparticles have been characterized by UV-vis spectroscopy, transmission electron microscopy, and X-ray diffraction. Comparison of FT-IR spectra of azacryptand before and after reaction revealed that azacryptand molecules reduce gold ions as the amino moieties in the molecules are oxidized to imino groups. The prepared gold nanoparticles show efficient surface-enhanced Raman scattering properties and can effectively catalyze reduction of 4-nitrophenol by sodium borohydride in aqueous solution. PMID- 17727873 TI - Network structure of collagen layers absorbed on LB film. AB - Elucidating the assembly mechanism of the collagen at interfaces is important. In this work, the structures of type I collagen molecules adsorbed on bare mica and on LB films of propanediyl-bis(dimethyloctadecylammonium bromide) transferred onto mica at zero surface pressure was characterized by AFM. On mica, the granular morphologies randomly distributed as elongated structures were observed, which were resulted from the interlacement of the adsorbed collagen molecules. On the LB films, the topographical evolution of the adsorbed collagen layers upon the increasing adsorption time was investigated. After 30 s, the collagen assembled into network-like structure composed of the interwoven fibrils, called as the first adlayer, which was attributed to its adsorption on the LB film by means of a limited number of contact points followed by the lateral association. One minute later, the second adlayer was observed on the top of the first adlayer. Up to 5 min, collagen layers, formed by inter-twisted fibrils, were observed. Under the same conditions after 1 min adsorption on LB film, the AFM image of the layer obtained in the diluted hydrochloric acid solution is analogous to the result of the sample dried in air, indicating that it is the LB film that leads to the formation of the network structure of collagen and the formation of the network structures of collagen layers is tentatively ascribed to the self-assembly of type I collagen molecules on LB film, not to the dewetting of the collagen solution during drying. PMID- 17727874 TI - Multi-faceted titanium glycolate and titania structures from room-temperature polyol process. AB - Multi-faceted microstructures of titanium glycolate have been produced by room temperature polyol process in which titanium alkoxide and polymethylene glycol were mixed rigorously and then the mixture was aged to settle down as white precipitate. Depending on types of titanium alkoxides and polymethylene glycols, stirring time, and composition, a variety of polygonal microrods were generated. Unlike unidentified structures produced from polyol process at elevated temperature, the titanium glycolate products obtained at room temperature revealed well-defined rod-like or plate-like structures with polygonal cross sections. Then, as-prepared titanium glycolate microstructures were transformed into higher refractive index titania of anatase or rutile phase by annealing. The characterization of as-prepared and annealed structures was conducted using scanning and transmission electron microscopes, X-ray diffractomer, and thermal analyzer for thermogravimetry and differential scanning calorimetry. PMID- 17727875 TI - Fabrication of photonic crystals with nigrosine-doped poly(MMA-co-DVB-co-MAA) particles. AB - A convenient approach was developed to fabricate monodisperse nigrosine-doped poly(methyl methacrylate-co-divinylbenzene-co-methacrylic acid) nanoparticles with different cross-linkage by soap-free emulsion polymerization at boiling status and swelling process. The dye-doped nanoparticles were used for the fabrication of colloidal crystal films and beads. It was found that nigrosine dye in the nanoparticles can efficiently depress the light scattering inside the colloidal crystal films and eliminate the iridescent effect in the photonic beads. These results make the colloidal crystals useful in photonic paper, bioassay, and so on. PMID- 17727876 TI - A new approach to the phenomena at the interfaces of finely dispersed systems. AB - A new idea has been applied for the elucidation of the electron and momentum transfer phenomena, at both rigid and deformable interfaces, in finely (micro-, nano-, atto-) dispersed systems. The electroviscoelastic behavior of, e.g., liquid/liquid interfaces (emulsions and double emulsions), is based on three forms of "instabilities"; these are rigid, elastic, and plastic. The events are understood as interactions between the internal (immanent) and external (incident) periodical physical fields. Since the events at the interfaces of finely dispersed systems must be considered at the molecular, atomic, and/or entities level it is inevitable to introduce the electron transfer phenomenon beside the classical heat, mass, and momentum transfer phenomena commonly used in chemical engineering. Therefore, an entity can be defined as the smallest indivisible element of matter that is related to the particular transfer phenomena. Hence, the entity can be either differential element of mass/demon, ion, phonon as quanta of acoustic energy, infon as quanta of information, photon, and electron. Three possible mathematical formalisms have been derived and discussed related to this physical formalism, i.e., to the developed theory of electroviscoelasticity. The first is the stretching tensor model, where the normal and tangential forces are considered, only in mathematical formalism, regardless of their origin (mechanical and/or electrical). The second is the classical integer-order van der Pol derivative model. Finally, the third model comprises an effort to generalize the previous van der Pol differential equations, both linear and nonlinear, where the ordinary time derivatives and integrals are replaced by corresponding fractional-order time derivatives and integrals of order p < 2 (p = n - delta, n = 1,2,delta << 1). In order to justify and corroborate a more general approach the obtained calculated results were compared to those experimentally measured using the representative liquid/liquid system. PMID- 17727877 TI - A bad day for quality control: sequential misplacement of left arm and left leg electrodes. PMID- 17727879 TI - The chemistry of protein catalysis. AB - We report, for the first time, on the statistics of chemical mechanisms and amino acid residue functions that occur in enzyme reaction sequences using the MACiE database of 202 distinct enzyme reaction mechanisms as a knowledge base. MACiE currently holds representatives from each Enzyme Commission sub-subclass where there is an available crystal structure and sufficient evidence in the primary literature for a mechanism. Each catalytic step of every reaction sequence in MACiE is fully annotated, so that it includes the function of the catalytic residues involved in the reaction and the chemical mechanisms by which substrates are transformed into products. We show that the most catalytic amino acid residues are histidine, cysteine and aspartate, which are also the residues whose side-chains are more likely to serve as reactants, and that have the greatest versatility of function. We show that electrophilic reactions in enzymes are very rare, and the majority of enzyme reactions rely upon nucleophilic and general acid/base chemistry. However, although rare, radical (homolytic) reactions are much more common than electrophilic reactions. Thus, the majority of amino acid residues perform stabilisation roles (as spectators) or proton shuttling roles (as reactants). The analysis presented provides a better understanding of the mechanisms of enzyme catalysis and may act as an initial step in the validation and prediction of mechanism in an enzyme active site. PMID- 17727880 TI - Design of disulfide-linked thioredoxin dimers and multimers through analysis of crystal contacts. AB - Disulfide bonds play an important role in protein stability and function. Here, we describe a general procedure for generating disulfide-linked dimers and multimers of proteins of known crystal structures. An algorithm was developed to predict sites in a protein compatible with intermolecular disulfide formation with neighboring molecules in the crystal lattice. A database analysis was carried out on 46 PDB coordinates to verify the general applicability of this algorithm to predict intermolecular disulfide linkages. On the basis of the predictions from this algorithm, mutants were constructed and characterized for a model protein, thioredoxin. Of the five mutants, as predicted, in solution four formed disulfide-linked dimers while one formed polymers. Thermal and chemical denaturation studies on these mutant thioredoxins showed that three of the four dimeric mutants had similar stability to wild-type thioredoxin while one had lower stability. Three of the mutant dimers crystallized readily (in four to seven days) in contrast to the wild-type protein, which is particularly difficult to crystallize and takes more than a month to form diffraction-quality crystals. In two of the three cases, the structure of the dimer was exactly as predicted by the algorithm, while in the third case the relative orientation of the monomers in the dimer was different from the predicted one. This methodology can be used to enhance protein crystallizability, modulate the oligomerization state and to produce linear chains or ordered three-dimensional protein arrays. PMID- 17727881 TI - Crystal structure of the radical SAM enzyme catalyzing tricyclic modified base formation in tRNA. AB - Wyosine and its derivatives, such as wybutosine, found in eukaryotic and archaeal tRNAs, are tricyclic hypermodified nucleosides. In eukaryotes, wybutosine exists exclusively in position 37, 3'-adjacent to the anticodon, of tRNA(Phe), where it ensures correct translation by stabilizing the codon-anticodon base-pairing during the ribosomal decoding process. Recent studies revealed that the wyosine biosynthetic pathway consists of multistep enzymatic reactions starting from a guanosine residue. Among these steps, TYW1 catalyzes the second step to form the tricyclic ring structure, by cyclizing N(1)-methylguanosine. In this study, we solved the crystal structure of TYW1 from Methanocaldococcus jannaschii at 2.4 A resolution. TYW1 assumes an incomplete TIM barrel with (alpha/beta)(6) topology, which closely resembles the reported structures of radical SAM enzymes. Hence, TYW1 was considered to catalyze the cyclization reaction by utilizing the radical intermediate. Comparison with other radical SAM enzymes allowed us to build a model structure complexed with S-adenosylmethionine and two [4Fe-4S] clusters. Mutational analyses in yeast supported the validity of this complex model structure, which provides a structural insight into the radical reaction involving two [4Fe-4S] clusters to create a complex tricyclic base. PMID- 17727883 TI - Surgical work output: is there room for increase? An analysis of surgical work effort from 1999 to 2003. AB - OBJECTIVE: To analyze physician work production over a 5-year period to discover trends in productivity. SUMMARY BACKGROUND DATA: Surgical workforce calculations over the past 25 years have projected major oversupply as well as looming shortages. Recent studies indicate that demand for surgical services will increase over the next two decades as the population ages and develops age related chronic diseases. This study examines actual physician productivity to determine whether there is capacity for increased work output in response to projected increases in demand. METHODS: Physician productivity data as measured by relative value units were obtained from the Medical Group Management Association Physician Compensation Reports for a 5-year period. Surgeons were compared with nonsurgeons and across subspecialties. RESULTS: Surgeon and nonsurgeon productivity in terms of relative value units remained relatively stable over the study period; surgical:nonsurgical productivity per provider was 1.30-1.46:1. CONCLUSIONS: Surgeons produce a significant amount of the total work in multi-specialty medical groups. These results may indicate that the surgical and general surgical workforce has reached a plateau with respect to clinical productivity. Predicted increases in demand for procedure-based work to care for the aging population are likely to be difficult to meet with the available workforce. PMID- 17727882 TI - Enhanced norepinephrine output during long-term desipramine treatment: a possible role for the extraneuronal monoamine transporter (SLC22A3). AB - To study the delay (2-6 weeks) between initial administration of norepinephrine reuptake inhibitor antidepressants and onset of clinical antidepressant action, we examined the effects of desipramine treatment on urinary and plasma catecholamines and their metabolites during the initial 6 weeks of treatment in depressed patients. Catecholamines and metabolites in 24-h urine collections and 8:00 a.m. plasma samples were measured at baseline and after 1, 4, and 6 weeks of desipramine treatment. Desipramine treatment produced significant increases in urinary norepinephrine (NE) and normetanephrine (NMN) and plasma NE at Weeks 4 and 6, but not at Week 1. The ratio of urinary NE/NMN was increased at Weeks 4 and 6, suggesting a reduction in the metabolism of NE to NMN at extraneuronal sites by Weeks 4 and 6. The increases in urinary NE and NMN and plasma NE at Weeks 4 and 6 of desipramine treatment were associated with a reduction in the conversion of NE to NMN. This would be compatible with a blockade of the extraneuronal monoamine transporter (organic cation transporter 3; SLC22A3) by NMN. Inhibition of the extraneuronal monoamine transporter may be an important component in the clinical pharmacology of the norepinephrine reuptake inhibitor antidepressant drugs, such as desipramine. PMID- 17727884 TI - Neither antioxidants nor COX-2 inhibition protect against esophageal inflammation in an experimental model of severe reflux. AB - BACKGROUND: Reflux-induced injury and oxidative stress result in esophageal inflammation and the potential for progression to intestinal metaplasia and adenocarcinoma. Proton-pump inhibitors represent the standard medical approach, but anti-inflammatories and antioxidants offer novel therapeutic possibilities. MATERIALS AND METHODS: Six weeks after an esophagojejunostomy reflux procedure, female Wistar rats (n = 100) were randomized to receive either an antioxidant (vitamin C, 8 mg or 28 mg/day), a cyclooxygenase-2 (COX-2) inhibitor (rofecoxib, 1 mg/day), or no therapy. After sacrifice 16 weeks later, esophageal injury was scored using pathologic and image analysis scoring. RESULTS: Esophagitis was present in all 63 animals completing the study and was severe in 27 (43%). No animal developed metaplasia or tumor. The extent of inflammation and esophageal ulceration were not significantly different between experimental groups. CONCLUSIONS: In this model of reflux injury, antioxidants and COX-2 inhibitors failed to ameliorate the severe inflammation induced. Further experimental designs should evaluate these novel approaches in less severe experimental models. PMID- 17727885 TI - Characterization of primary breast carcinomas grown in three-dimensional cultures. AB - BACKGROUND: The process of progression and spread of cancer is not easily replicated in animal models and is difficult to examine in vitro. This is particularly true for human primary breast carcinoma cells, whose in vitro growth is shown to be limited to one or two passages in monolayer culture. Three dimensional (3D) growth of breast cancer cells suggests that cell aggregates grown in this manner have many similarities to in vivo behavior. MATERIALS AND METHODS: Primary tumors obtained from five breast cancer patients were grown in 3D cultures using the rotating-wall vessel bioreactor. Tumor aggregates were assessed for DNA ploidy, cell cycle kinetics, and expression of tumor markers and cytokines. Comparisons between fresh tumor cells and 3D aggregates were performed. RESULTS: All five breast cancers were found to be aneuploid after 3D culture, with elevated S-phase fractions. Reverse transcription-polymerase chain reaction analyses revealed mRNA expression of HER2/neu, H-ras, K-ras, p53, transforming growth factor-alpha, transforming growth factor-beta, interleukin-1, and interleukin-6 in 3D-grown tumor cells; in most cases, expression appeared increased when compared with mRNA obtained from freshly isolated primary tumor cells. CONCLUSIONS: After prolonged 3D growth in the rotating wall bioreactor, complex tissue-like constructs of primary breast tumor cells exhibited significantly increased proliferative activity in conjunction with oncogene activation and developed into aggressive aneuploid populations. PMID- 17727886 TI - Serum protein profiling to identify high-risk neuroblastoma: preclinical relevance of blood-based biomarkers. AB - INTRODUCTION: Development of early detection assays for advanced stage neuroblastoma (NB) remains elusive. We have previously shown that serum protein profiling technologies can differentiate healthy from NB children. As various sources of patient related bias exist in serum proteins, we hypothesized a well controlled animal model may provide a better method to identify tumor blood-based markers during NB progression. METHODS: Tumors were induced in the left kidneys of nude mice by the injection of cultured human NB cells (10(6)). Sera were collected from control and tumor-bearing mice at 2, 4, and 6 wk. Albumin-depleted sera were subjected to comparative proteomic profiling using 2D gel electrophoresis. Paired samples at each time point were analyzed and differentially expressed serum proteins were identified by mass spectrometry. Additionally, sera proteomic analysis from children with Stage IV NB and healthy controls were performed. RESULTS: Overexpression of five mouse serum proteins [alpha(1)-acid glycoprotein, alpha(1)-antitrypsin, alpha(2)-macroglobulin, serum amyloid P-component, and serum amyloid A) were found only in NB-bearing mice. Changes in protein abundance were found to increase 2.5-fold (P < or = 0.05) between 2-, 4-, and 6-wk old mice. Underexpression of immunoglobulin kappa chain constant region was observed in the sera of tumor bearing mice compared with controls (2.5-fold, P < or = 0.05). Among NB patients, alpha(1)-acid glycoprotein, apolipoprotein A-IV, haptoglobin, and serum amyloid A were found to be up-regulated. CONCLUSIONS: We identified distinct acute phase proteins that show up-regulation in both an animal tumor model and high-risk NB patients. As these serum proteins have been recognized as markers of tumor progression and prognosis in human malignancies, the validation of these polypeptides may enable serum proteomic profiling to become a valuable tool for identifying high-risk NB. PMID- 17727887 TI - Repairing large duodenal injuries in dogs by expanded polytetrafluoroethylene patch. AB - BACKGROUND: One of the most challenging problems in clinical surgery is management of injured duodenum. In this experimental study, we treated large duodenal defects by an expanded polytetrafluoroethylene (ePTFE, Gore-Tex; W.L. Gore, Elkton, MD) soft-tissue patch and compared it with the jejunal serosal patch. MATERIALS AND METHODS: A duodenal defect (about 50% of the total circumference) was created in the second portion of the duodenum in 20 dogs. The effectiveness and gross and histological examinations of the ePTFE patch technique was compared with the jejunal serosal patch. RESULTS: No significant difference was found in early survival rates (90.9% versus 88.9%; P = 0.711). The whole grafted area was covered by neomucosa at the end of the sixth week in all animals with the ePTFE patch. The scar was small; no significant narrowing of lumen was noted and serosal healing was uniformly complete. In histological examination, complete coverage of the ePTFE grafts by neomucosa consisting of columnar epithelium with short villous formations was observed. CONCLUSION: Use of the ePTFE patch method is easy, reliable, and comparable to the jejunal serosal patch. It can be used in the treatment of large duodenal defects, which cannot be repaired by duodenorraphy. PMID- 17727888 TI - A comparative analysis between survivors and nonsurvivors with antibody mediated cardiac allograft rejection. AB - BACKGROUND: Antibody mediated rejection (AMR) is an important cause of graft loss in the post heart transplant period. The following study was conducted to determine differences between survivors and nonsurvivors who developed post heart transplant AMR. METHODS: We retrospectively reviewed the charts of patients who received a heart transplant between January 1993 and December 2002. Patients with biopsy proven AMR were identified. This group was divided into survivors and nonsurvivors. Groups were compared with regards to demographics, T-cell flow panel of reactive antibodies (PRA), flow cross-matches (anti-donor HLA Class I and II), and short- and long-term outcomes. Results of endomyocardial biopsies were collected to allow calculation of sensitivity, specificity, negative- and positive predictive values as well as accuracy of immunoglobulins and complement split products in association to death. RESULTS: A total of 65 patients (8.9%) were diagnosed with AMR. Mean age was 48 y (range: 8-68 y) and 53.8% were males. Episodes of hemodynamic instability associated with AMR were observed in 37% of patients. Only two deaths were directly attributed to acute AMR. Nearly 20% of AMR patients developed transplant coronary artery disease. Univariate analysis identified T-PRA (P < 0.001), mean T-cell molecules of equivalent soluble fluorochrome (MESF) (P < 0.001) and mean B-cell MESF (P < 0.001) as possible factors associated with death. Neither demographics of complement split products were associated to late death. CONCLUSION: When studying patients with AMR, pretransplant T-PRA, T-cell, and B-cell MESF may identify individuals at risk of late death. PMID- 17727889 TI - Functional neuroimaging in multiple sclerosis with radiolabelled glia markers: preliminary comparative PET studies with [11C]vinpocetine and [11C]PK11195 in patients. AB - With the purpose of demonstrating the use of positron emission tomography (PET) and radiolabelled glia markers to indicate regional cerebral damage, we measured with PET in four young multiplex sclerosis (MS) patients in two consecutive measurements the global and regional brain uptake as well as regional distribution and binding potential (BP) of [(11)C]vinpocetine and [(11)C]PK11195. Both ligands showed increased uptake and BP in the regions of local brain damage. However, regional BP values for [(11)C]vinpocetine were markedly higher than those for [(11)C]PK11195. This feature of the former radioligand may be related to its high brain uptake and marked affinity to the peripheral benzodiazepine receptor binding sites (PBBS), characteristic for glia cells. As local brain traumas entail reactive glia accumulation in and around the site of the damage, the present findings may indicate that [(11)C]vinpocetine marks the place or boundaries of local brain damage by binding to the PBBS present in glia cells, which, in turn, accumulate in the region of the damage. The present findings (i) confirm earlier observations with [(11)C]PK11195 as a potential glia marker in PET studies and (ii) support the working hypothesis that [(11)C]vinpocetine is a potentially useful PET marker of regional and global brain damage resulting in glia accumulation locally or globally in the human brain. The comparative analysis of the two ligands indicate that [(11)C]vinpocetine shows a number of characteristics favourable in comparison with [(11)C]PK11195. PMID- 17727890 TI - Incidence and subtypes of dementia in three elderly populations of central Spain. AB - OBJECTIVE: To assess age-, gender, and subtype-specific incidence rates of dementia in three populations in central Spain using data from the Neurological Disorders in Central Spain (NEDICES), a population-based survey of elderly participants. METHODS: Individuals were evaluated at baseline (1994-1995) and at follow-up (a median of 3.2 years later in 1997-1998). The evaluation included a screening questionnaire for dementia and a neurological assessment, when possible. RESULTS: Of 5278 participants evaluated at baseline, there were 306 prevalent dementia cases. One hundred and sixty-one incident dementia cases were identified among 3,891 individuals assessed at follow-up. The large majority had Alzheimer's disease (AD): 115 (71.4%) AD, 18 (11.2%) vascular dementia (VaD), 11 (6.8%) dementia associated with parkinsonism, 11 (6.8%) undetermined etiology, and 6 (3.7%) secondary dementia. Average annual incidence rates (per 1,000 person years) in the population aged 65 to 90 and over years, adjusted to the standard European population, were 10.6 (95% CI, 8.9 to 12.3) for dementia, 7.4 (95% CI=6.0 to 8.8) for AD, and 1.4 (95% CI=0.6 to 2.3) for VaD. Age-specific incidence rates of dementia and AD increased exponentially with advancing age. Age, stroke and illiteracy were independent risk factors for dementia and AD. Aggregation of vascular risk factors was related to a higher risk of both VaD and AD. CONCLUSIONS: In the NEDICES study, incidence of dementia increased with age beyond age 85 and AD was the most frequent type of dementia. The risk of AD and VaD increased with the number of vascular risk factors. PMID- 17727891 TI - The association of the regulatory region of the presenilin-2 gene with Alzheimer's disease in the Northern Han Chinese population. AB - Presenilin-2 is one of the causative genes for familial Alzheimer's disease (FAD). Polymorphism of the promoter region of the presenilin-2 gene (PSEN2) has recently been reported in a Russian population to be associated with sporadic Alzheimer's disease (SAD). The purpose of this case-control study was to determine whether SAD is associated with the PSEN2 gene polymorphism in a Chinese population. We examined PSEN2 and APOE genotypes in 200 SAD patients and an equal number of age- and sex-matched controls from the same community, using the PCR RFLP method. Allelic and genotypic distributions were performed using the Pearson Chi-square test for homogeneity. The interactions between variables were examined by logistic regression. The results revealed no significant differences in the frequency of the +A/-A polymorphism between AD and controls (chi(2)=3.857, p=0.145). However, in the subgroup of APOE epsilon4 non-carriers, there were significant differences in the distributions of both alleles (chi(2)=6.095, p=0.047) and genotypes (chi(2)=4.433, p=0.035) of the PSEN2 promoter in AD compared with controls. In APOE epsilon4 non-carrier group, with +A/+A as a reference, the -A/-A genotype was associated with a 4.657-fold increased risk for AD (chi(2)=5.783, p=0.016, OR=4.657, 95% CI=1.195-18.152). Using logistic analysis, there were no statistical interactions between PSEN2 and APOE genotypes, or between PSEN2 genotypes and age of onset. It is concluded that in the Northern Han Chinese population, the +A/-A polymorphism of the PSEN2 promoter is a moderate genetic risk factor for developing SAD, independent of the APOE epsilon4 allele. PMID- 17727892 TI - One-hit stochastic decline in a mechanochemical model of cytoskeleton-induced neuron death II: transition state metastability. AB - This is the second of two papers in which we study a mathematical model of cytoskeleton-induced neuron death. Recent evidence indicates that aggravated assembly or destruction of the cytoskeleton can trigger programmed death in neurons, by mechanisms as yet poorly understood. In our model, assembly control of the neuronal cytoskeleton interacts with both cellular stress levels and cytosolic free radical concentrations to trigger neurodegeneration. This trigger mechanism is further modulated by a diffusible toxic factor released from dying neurons. In the companion report we established that the model relates the observed general patterns of neuron decline to specific scales of cytoskeleton reorganization and cell-cell interaction strength. In this paper we study the transit of neurons through states intermediate between initial viability and cell death in our model. We find that the stochastic flow of neuron fate, from viability to cell death, self-organizes into two distinct temporal phases. There is a rapid relaxation of the initial neuron population to a more disordered phase that is long-lived, or metastable, with respect to the time scales of change in single cells. Strikingly, cellular egress from this metastable phase follows the one-hit kinetic pattern of exponential decline now established as a principal hallmark of cell death in neurodegenerative disorders. Intermediate state metastability may therefore be an important element in the systems biology of one hit neurodegeneration. PMID- 17727893 TI - From inclusive fitness to fixation probability in homogeneous structured populations. AB - The methods of inclusive fitness provide a powerful analysis of the action of selection on social behaviour. The key component of this analysis is the concept of relatedness R. In infinite populations, a standard method of calculating relatedness coefficients is through coefficients of consanguinity using the notion of genetic identity by descent. In this paper, we show that this approach can also be made to work in finite populations and we assume here that the population has a homogeneous structure, such as an island model. We demonstrate that, under the assumption that genetic effects are small and additive, the resulting formulation of inclusive fitness is equivalent to other significant measures of selection in finite populations, including the change in average allele frequency and fixation probability. The results are illustrated for a model of the evolution of cooperation in a finite island population. PMID- 17727895 TI - Doping in sports: the pediatric perspective. PMID- 17727894 TI - Food web structure and interaction strength pave the way for vulnerability to extinction. AB - This paper focuses on how food web structure and interactions among species affects the vulnerability, due to environmental variability, to extinction of species at different positions in model food webs. Vulnerability is here not measured by a traditional extinction threshold but is instead inspired by the IUCN criteria for endangered species: an observed rapid decline in population abundance. Using model webs influenced by stochasticity with zero autocorrelation, we investigate the ecological determinants of species vulnerability, i.e. the trophic interactions between species and food web structure and how these interact with the risk of sudden drops in abundance of species. We find that (i) producers fulfil the criterion of vulnerable species more frequently than other species, (ii) food web structure is related to vulnerability, and (iii) the vulnerability of species is greater when involved in a strong trophic interaction than when not. We note that our result on the relationship between extinction risk and trophic position of species contradict previous suggestions and argue that the main reason for the discrepancy probably is due to the fact that we study the vulnerability to environmental stochasticity and not extinction risk due to overexploitation, habitat destruction or interactions with introduced species. Thus, we suggest that the vulnerability of species to environmental stochasticity may be differently related to trophic position than the vulnerability of species to other factors. Earlier research on species extinctions has looked for intrinsic traits of species that correlate with increased vulnerability to extinction. However, to fully understand the extinction process we must also consider that species interactions may affect vulnerability and that not all extinctions are the result of long, gradual reductions in species abundances. Under environmental stochasticity (which importance frequently is assumed to increase as a result of climate change) and direct and indirect interactions with other species some extinctions may occur rapidly and apparently unexpectedly. To identify the first declines of population abundances that may escalate and lead to extinctions as early as possible, we need to recognize which species are at greatest risk of entering such dangerous routes and under what circumstances. This new perspective may contribute to our understanding of the processes leading to extinction of populations and eventually species. This is especially urgent in the light of the current biodiversity crisis where a large fraction of the world's biodiversity is threatened. PMID- 17727897 TI - Integrative assessment of organotin contamination in a southern European estuarine system (Ria de Aveiro, NW Portugal): tracking temporal trends in order to evaluate the effectiveness of the EU ban. AB - Organotin (OT) compounds have been used as biocide agents in antifouling paints since the mid 1960s and are now ubiquitous in the marine environment. Due to their high toxicity to non-target species they were banned from antifouling paints in the European Union in 2003 (2002/62/EC directive). The aim of the present work is to assess any obvious decline of the OT environmental levels at Ria de Aveiro (NW Portugal) after the ban. The organotins - monobutyltin (MBT), dibutyltin (DBT), tributyltin (TBT), monophenyltin (MPT), diphenyltin (DPT), triphenyltin (TPT), monoctyltin (MOT), dioctyltin (DOT) and trioctyltin (TOT) - were quantified in the gastropod Nassarius reticulatus, in the mussel Mytilus galloprovincialis and in sediments. Imposex (imposition of male characters on females of gonochorist gastropods) in N. reticulatus was additionally used as a biomarker of TBT pollution. Time comparisons show a slight decrease of imposex between 2003 and 2005 probably as a consequence of the EU ban, though in some cases this trend seems to have started earlier since 2000. The fraction of TBT relatively to its metabolites has been decreasing over the last years but still remains high suggesting that there are still recent inputs of this compound into the study area. PMID- 17727896 TI - Isoform-specific downregulation of peroxiredoxin in human failing myocardium. AB - Peroxiredoxins (Prx) are a family of antioxidant thioredoxin or glutathione dependent peroxidases. The major functions of Prx comprise modulation of signalling cascades that apply hydrogen peroxide (H(2)O(2)) and cellular protection against oxidative stress. Nothing is known about Prx isoforms in human myocardium. We investigated the protein expression of Prx isoforms 1-6 in human non-failing (NF, donor hearts, n=6, male, age: 53.3+/-2.1 years) and failing myocardium (DCM, orthotopic heart transplantation, dilated cardiomyopathy, n=15, male, 57.0+/-1.7 years). In addition, we performed immunohistochemical stainings and measured Prx 4 mRNA expression levels (RNAse protection assay). The protein expression of Prx 1-2 was similar in NF and DCM. The protein expression of Prx 3 6 and the mRNA-expression of Prx 4 were decreased in DCM. Immunohistochemical analyses provided evidence that all Prx isoforms are present in cardiomyocytes and endothelial cells. Whereas Prx 1-5 staining was more pronounced in endothelial cells, Prx6 staining was more evident in cardiomyocytes. This study provides evidence that Prx are differentially regulated in DCM. The selective downregulation of peroxiredoxin 3-6 isoforms may point towards a subcellular specific dysregulation of the antioxidative defence during the development of DCM. PMID- 17727898 TI - Intra- and inter-specific variability in total and methylmercury bioaccumulation by eight marine fish species from the Azores. AB - We relate fish biological and ecological characteristics to total and organic mercury concentrations to determine whether accumulation is influenced by trophic level, Hg concentration in the diet, and vertical distribution. Levels of total mercury and methylmercury were determined in the muscle tissue of eight species of fish: Pagellus acarne, Trachurus picturatus, Phycis phycis, P. blennoides, Polyprion americanus, Conger conger, Lepidopus caudatus and Mora moro, caught in the Azores. All such fishes are commercially valuable and were selected to include species from a wide range of vertical distributions from epipelagic (<200 m) to mesopelagic (>300 m) environments. Methylmercury was the major form accumulated in all species, comprising an average of 88.1% of total mercury. Concentrations of mercury (total and methylmercury) increased with age, length and weight. Based on data from other studies, mercury concentrations in fish diet were estimated. Mercury levels in food ranged from 0.08 to 0.32 ppm, dry weight. Hg concentrations in the food and in muscle tissue from different species were positively correlated. Total Hg levels in the muscles were approximately nine times those estimated in food. Total mercury concentrations in muscle were positively correlated with both trophic level and median depth. Such enhanced mercury bioaccumulation in relation to depth appears to be determined primarily by concentrations in food and ultimately by water chemistry, which controls mercury speciation and uptake at the base of the food chain. PMID- 17727899 TI - Effects of angiotensin II on flux rise time in rats (a time index of laser Doppler flowmetry) and its relation with microvascular structures. AB - Laser Doppler flowmetry (LDF) is a popular method for monitoring the microcirculation, but it does not provide absolute measurements on local area with small size microvessels. Instead, the mean flux response is generally compared between before and after stimulus. In this study, we proposed a new dimension for comparing the LDF signals. The flux rise time (FRT), a time index with absolute physical quantity, was extracted from noisy LDF signals using a pulsatile-based synchronized-averaging method. We investigated the changes of FRT and its relation to the microvascular resistance (MVR) under the selective effects of angiotensin II (Ang II) on the kidney and the plantar palm. Ang II was infused into anesthetized Wistar Kyoto rats via the femoral vein for 1 h. Using the heartbeat as a self-trigger, we calculated the FRT and MVR from the renal cortical flux, plantar palm flux, and abdominal aortic blood pressure recorded before, during, and after Ang II infusion. The control FRT values were similar in the two vascular beds. Ang II decreased the renal cortical flux but significantly increased the FRT and MVR of both beds. The effects on the renal FRT and renal MVR were selectively larger than those on the palm FRT and palm MVR. The results indicate that the changes of FRT and MVR are similarly physiologically linked with microvascular structures. As an MVR-related absolute physical quantity, the FRT could be developed as a monitoring tool in physiological, pathological, and pharmacological investigations. PMID- 17727900 TI - Plasmid expression of mutS, -L and/or -H gene in Escherichia coli dam cells results in strains that display reduced mutation frequency. AB - Escherichia colidam cells have an active but non-directed mismatch repair system; therefore, assembly of MutSLH complex at a mismatched base pair can result in MutH-mediated cleavage of GATC sites in both DNA strands. Unpaired double-strand breaks on a fraction of the replication errors occurring in dam cells presumably cause cell death, selectively eliminating these putative mutants from the population. We show that E. colidam cells transformed with plasmids containing either the mutS, mutL or mutH gene display a mutation frequency three to eight times lower than that of the parental dam strain, due to increased mismatch stimulated cell killing. Transformed strains are also more susceptible to killing by the base analogue 2-aminopurine. However, dam and dam transformed cells have similar duplication time, proportion of live/dead cells and morphology. PMID- 17727901 TI - Diffuse axonal injury due to traumatic brain injury alters inhibition of imitative response tendencies. AB - It is well known that traumatic brain injury particularly affects the frontal lobes. Consequently, patients often suffer from executive dysfunction and behavioral disturbances. Accordingly, our study aimed at investigating patients after traumatic brain injury with two tasks involving different functional processes and structural networks supported by the frontal lobes. Two paradigms were applied: the Stroop color-word task and a task in which subjects had to inhibit imitative response tendencies. We selected a patient group solely with diffuse axonal injury, as this type of injury is homogenous and is correlated with cognitive dysfunction more than focal contusions. To evaluate long-term effects most relevant for rehabilitation, we selected a patient group whose brain injuries dated back several years. Our results show that patients with diffuse axonal injury inhibited imitative responses more successfully than control subjects, whereas executive processes examined with the Stroop task were unaltered. Interestingly, impairments were tightly correlated both with the length of the post-traumatic amnesia predicting outcome in traumatic brain injury and with behavioral disturbances. Impairments in the imitation-inhibition task may indicate alterations in an anterior frontomedian neural network even years after traumatic brain injury. PMID- 17727902 TI - Prenatal stress does not impair coping with challenge later in life. AB - This study investigated whether the effects of prenatal social stress are pathological consequences of an adverse environment; or whether mothers adjust their offspring to prevalent social conditions. As a prenatal stressor social instability was used: we studied male guinea pig offspring whose mothers lived in a stable social environment (SE-sons) or in an unstable social environment during pregnancy (UE-sons). Eight experimental groups were established, consisting of one SE-son, one UE-son and five females, respectively. In all groups females were regularly exchanged to create a situation of social instability. We hypothesised that if mothers prenatally adapt their offspring to an unstable social environment, UE-sons will be dominant, display agonistic and courtship behaviour more frequently, have higher body weights, be less reactive to moderate stressors and have higher testosterone concentrations than SE-sons. Our results revealed no significant differences between SE- and UE-sons concerning behaviour, dominance status, body weights, cortisol or testosterone. However, we found differences between dominant and subdominant males. Subdominant males had significantly higher cortisol levels than dominant males, pointing to a higher degree of stress. Regarding testosterone, dominant males had higher testosterone levels directly after the establishment of dominance hierarchies. Thus, these results do not provide evidence that mothers adjust their offspring prenatally to prevailing social conditions. They also do not support the hypothesis that instability of the mother's environment during pregnancy inevitably results in behavioural disorders or pathological endocrine profiles. Rather do the sons' behavioural and endocrine responses later in life reflect typical reactions to socially challenging situations. PMID- 17727903 TI - Flavour-flavour learning occurs automatically and only in hungry participants. AB - A novel flavour may become liked if it is presented repeatedly and in combination with a second flavour that is already liked. Conceptually, this 'flavour-flavour learning' is important, because it can account for many of our everyday food and flavour preferences. However, relatively little is known about the underlying process because learning paradigms have lacked reliability. Based on previous research we explored whether learning is determined by three variables; i) hunger state, ii) demand and contingency awareness, and iii) dietary restraint. Participants (male n=15/female n=15) consumed three different and novel-tasting fruit teas. One of the teas had a non-caloric sweetener added (CS+) and two were unsweetened (CS-). Before and after this training the participants ranked their preference for unsweetened versions of the three teas. We found that the training increased preference for the CS+ relative to the CS- teas. However, this effect was only found in hungry participants. We also found little evidence that learning was related to whether the participants could identify (recognition test) the specific tea that had been sweetened during training, suggesting that the underlying process is automatic and it operates outside conscious awareness. Learning was not predicted by dietary restraint (measured using the DEBQ-R scale). Together, these findings provide further evidence for a linkage between flavour-flavour learning and flavour-nutrient learning. PMID- 17727904 TI - Sex and diet affect the behavioral response of rats to chronic mild stressors. AB - To investigate the interaction between sex, stressors, and dietary choice in rats, a preferred diet under the influence of chronic mild stressors was empirically determined to consist of soybeans and cookies in addition to lab chow. This preferred mixed diet was then tested for its influence on several behavioral tests at the end of prolonged exposure to the potential stressors. Rats of both sexes decreased their frequency of rearing but increased their attention to novelty in response to stressors. In the elevated plus maze, diet interacted with exposure to stressors to influence time spent in the open arm in females but not males. In the forced swim test, females but not males fed the mixed diet showed increased immobility, whether exposed to stressors or not. Finally, females but not males showed a differential effect of diet under stressors on the sucrose preference test, but this result was confounded by estrus cycling, demonstrating the importance of this factor in analyzing behavior in females. These results suggest that male and female rats differ in their susceptibility to the behavioral-modifying influences of stressors. And to the extent that diet serves as a coping mechanism, it does so differently in males and females. PMID- 17727905 TI - Impact of porcine group A rotavirus co-infection on porcine epidemic diarrhea virus pathogenicity in piglets. AB - Porcine epidemic diarrhea virus (PEDV) and porcine group A rotavirus (PGAR) are the main causative agents of acute diarrhea in piglets. In South Korea, PGAR is prevalent in piglets naturally infected with PEDV. Piglets naturally co-infected with PEDV and PGAR appeared to have severe and prolonged diarrhea that was distinct from that commonly observed. The aim of this study was to determine the impact of PGAR co-infection on PEDV pathogenicity in piglets. Thirty-six colostrum-deprived, one-day old, Large White-Duroc crossbred pigs were randomly divided into four equal groups: PEDV, PEDV/PGAR, PGAR, and control groups. The piglets were euthanized at 1, 2, or 3 days post-inoculation (DPI) to measure the villous height:crypt depth (VH:CD) ratio and to collect fecal samples for RT-PCR and virus isolation. No significant differences in mean VH:CD ratio and clinical symptoms (diarrhea, vomiting, dehydration, and anorexia) were observed between the PEDV/PGAR-infected and PEDV-infected groups of piglets at 1, 2 and 3 DPI; however, at 2 and 3 DPI, PGAR was detected in all fecal samples by RT-PCR and virus isolation. These findings failed to detect any interaction between PEDV and porcine rotavirus in the small intestines of piglets, suggesting that concurrent infection of PGAR may not synergistically enhance intestinal villous atrophy of piglets with PEDV disease. We propose that the severe diarrhea exhibited in PEDV and PGAR co-infected piglets may be more associated with the immunity level of the host rather than to any synergistic effect of PGAR on PEDV enteritis. PMID- 17727906 TI - Mites in clinical stool specimens: potential misidentification as helminth eggs. AB - We report the finding of unexpected microscopic oval structures in clinical stool samples processed by AFIP/Medicina Laboratorial, a laboratory performing routine clinical analysis in Sao Paulo, Brazil. Surprisingly, these objects were identified as mite eggs, sometimes accompanied by adult mites. Because misidentification of mite eggs as helminth ova may lead to erroneous treatment with far-reaching consequences, we sought to verify the frequency of adult mites and mite eggs among a number of processed stool specimens. Given their similarity to some helminth eggs, it is important that clinical laboratories recognize these structures, especially in geographic regions where intestinal parasitosis is prevalent. PMID- 17727907 TI - Host defence peptides-a bridge between the innate and adaptive immune responses. AB - At the interface of innate and adaptive immunity, host defence peptides have been shown to enhance the overall immune response, where peptide expression and activity map onto aspects of the response to infection. This includes the ability to chemoattract phagocytic and antigen-presenting cells, and regulate the host cytokine response. Effects of peptides on B- and T-lymphocyte function, including B-cell activation and antibody production, cytotoxic T-cell and natural-killer cell killing, and T-helper cell function, are starting to demonstrate that some of these peptides are capable of directing a prolonged cellular and humoral response to a pathogen. PMID- 17727908 TI - Synthesis of daidzein 7-O-beta-D-glucuronide-4'-O-sulfate. AB - The first synthesis of daidzein 7-O-beta-D-glucuronide-4'-O-sulfate, a mixed conjugate of an important dietary phytoestrogen is described. PMID- 17727909 TI - Survival and aging in the wild via residual demography. AB - Information about the age distribution and survival of wild populations is of much interest in ecology and biodemography, but is hard to obtain. Established schemes such as capture-recapture often are not feasible. In the proposed residual demography paradigm, individuals are randomly sampled from the wild population at unknown ages and the resulting captive cohort is reared out in the laboratory until death. Under some basic assumptions one obtains a demographic convolution equation that involves the unknown age distribution of the wild population, the observed survival function of the captive cohort, and the observed survival function of a reference cohort that is independently raised in the laboratory from birth. We adopt a statistical penalized least squares method for the deconvolution of this equation, aiming at extracting the age distribution of the wild population under suitable constraints. Under stationarity of the population, the age density is proportional to the survival function of the wild population and can thus be inferred. Several extensions are discussed. Residual demography is demonstrated for data on fruit flies Bactrocera oleae. PMID- 17727911 TI - cis-Acting core RNA elements required for negative-strand RNA synthesis and cap independent translation are separated in the 3'-untranslated region of Red clover necrotic mosaic virus RNA1. AB - The genome of Red clover necrotic mosaic virus (RCNMV) is positive-sense and divided into RNA1 and RNA2. RNA1 has a translation enhancer element (3' TE-DR1) in the 3' untranslated region (UTR) that substitutes for a 5' cap. In this study, we determined the regions required for cap-independent translation and RNA synthesis in the 3' UTR of RNA1 using a cell-free extract of evacuolated BY-2 protoplasts (BYL) and by an assay in BY-2 protoplasts. The use of capped viral RNA transcripts in the BYL system allowed us to distinguish the effects of introduced mutations on cap-independent translation and negative-strand RNA synthesis of RNA1. We found that the core RNA element of 3' TE-DR1 essential for cap-independent translation of RNA1 is dispensable for negative-strand RNA synthesis. Thus, cis-acting RNA elements essential for cap-independent translation are separated from those required for negative-strand RNA synthesis in the 3' UTR of RCNMV RNA1. PMID- 17727910 TI - Stable cell lines expressing high levels of the herpes simplex virus type 1 LAT are refractory to caspase 3 activation and DNA laddering following cold shock induced apoptosis. AB - The herpes simplex virus type 1 (HSV-1) latency associated transcript (LAT) gene's anti-apoptosis activity plays a central, but not fully elucidated, role in enhancing the virus's reactivation phenotype. In transient transfection experiments, LAT increases cell survival following an apoptotic insult in the absence of other HSV-1 genes. However, the high background of untransfected cells has made it difficult to demonstrate that LAT inhibits specific apoptotic factors such as caspases. Here we report that, in mouse neuroblastoma cell lines (C1300) stably expressing high levels of LAT, cold shock induced apoptosis was blocked as judged by increased survival, protection against DNA fragmentation (by DNA ladder assay), and inhibition of caspase 3 cleavage and activation (Western blots). To our knowledge, this is the first report providing direct evidence that LAT blocks two biochemical hallmarks of apoptosis, caspase 3 cleavage and DNA laddering, in the absence of other HSV-1 gene products. PMID- 17727912 TI - Immunocompetent syngeneic cotton rat tumor models for the assessment of replication-competent oncolytic adenovirus. AB - Oncolytic adenoviruses as a treatment for cancer have demonstrated limited clinical activity. Contributing to this may be the relevance of preclinical animal models used to study these agents. Syngeneic mouse tumor models are generally non-permissive for adenoviral replication, whereas human tumor xenograft models exhibit attenuated immune responses to the vector. The cotton rat (Sigmodon hispidus) is susceptible to human adenovirus infection, permissive for viral replication and exhibits similar inflammatory pathology to humans with adenovirus replicating in the lungs, respiratory passages and cornea. We evaluated three transplantable tumorigenic cotton rat cell lines, CCRT, LCRT and VCRT as models for the study of oncolytic adenoviruses. All three cells lines were readily infected with adenovirus type-5-based vectors and exhibited high levels of transgene expression. The cell lines supported viral replication demonstrated by the induction of cytopathogenic effect (CPE) in tissue culture, increase in virus particle numbers and assembly of virions seen on transmission electron microscopy. In vivo, LCRT and VCRT tumors demonstrated delayed growth after injection with replicating adenovirus. No in vivo antitumor activity was seen in CCRT tumors despite in vitro oncolysis. Adenovirus was also rapidly cleared from the CCRT tumors compared to LCRT and VCRT tumors. The effect observed with the different cotton rat tumor cell lines mimics the variable results of human clinical trials highlighting the potential relevance of this model for assessing the activity and toxicity of oncolytic adenoviruses. PMID- 17727914 TI - Dye house wastewater treatment through advanced oxidation process using Cu exchanged Y zeolite: a heterogeneous catalytic approach. AB - Catalytic wet hydrogen peroxide oxidation of an anionic dye has been explored in this study. Copper(II) complex of NN'-ethylene bis(salicylidene-aminato) (salenH2) has been encapsulated in super cages of zeolite-Y by flexible ligand method. The catalyst has been characterized by Fourier transforms infra red spectroscopy, X-ray powder diffractograms, Thermo-gravimetric and differential thermal analysis and nitrogen adsorption studies. The effects of various parameters such as pH, catalyst and hydrogen peroxide concentration on the oxidation of dye were studied. The results indicate that complete removal of color has been obtained after a period of less than 1h at 60 degrees C, 0.175M H2O2 and 0.3g l(-1) catalyst. More than 95% dye removal has been achieved using this catalyst for commercial effluent. These studies indicate that copper salen complex encapsulated in zeolite framework is a potential heterogeneous catalyst for removal of color from wastewaters. PMID- 17727913 TI - Occurrence of PCBs, PCDD/Fs, PBDEs and DDTs in Spanish breast milk: enantiomeric fraction of chiral PCBs. AB - Concentrations and congener specific profile of DDTs, PCBs and PCDD/Fs have been determined in a number of Spanish breast milk samples. The concentrations found indicate a decreasing tendency compared to previous data from the 1990s. Mean concentrations of 238 ng/g fat weight, 111 ng/g fat weight and 82.1 pg/g fat weight were found for DDTs, PCBs and 2,3,7,8-PCDD/Fs, respectively. When the WHO TEQs were calculated, PCDD/Fs was the family contributing with the highest percentage to the total (62-84%), followed by the non-ortho PCBs (10-25%) and the mono-ortho PCBs (5-24%). The congener specific accumulation patterns found were comparable to those reported in other studies in industrialised countries. In addition, the levels of 9 PBDEs congeners have been also determined in the breast milk samples. The concentrations ranged from 0.04 to 1.38 ng/g fat weight. The enantiomeric enrichment of a number of chiral PCBs in the breast milk samples, including congeners 84, 91, 95, 132, 135, 149, 171, 174, 176 and 183, has also been studied, for some of them for the first time in this matrix. PMID- 17727915 TI - A new twist on an old regression: transfer of chemicals to beef and milk in human and ecological risk assessment. AB - Exposure of humans to chemicals in beef or milk is part of almost all risk evaluation procedures carried out to reduce emissions or to remediate sites. Concentrations of substances in these livestock products are often estimated using log-log regressions that relate the biotransfer factor BTF to the octanol water partition ratio K(ow). However, the correctness of these empirical correlations has been questioned. Here, we compare them to the mechanistic model OMEGA that describes the distribution of substances in organisms by integrating theory on chemical fugacity and biological allometry. OMEGA has been calibrated and validated on thousands of laboratory and field data, reflecting many chemical substances and biological species. Overall fluxes of water, food, tissue (growth), milk and stable substances calculated by OMEGA are within a factor of two from independent data obtained in experiments. Rate constants measured for elimination of individual compounds of a recalcitrant nature vary around the level expected from the model for output to faeces and milk. Both data and model suggest that biotransfer BTF of stable substances to beef and milk is independent of the octanol-water partition ratio K(ow) in the range of 10(3)-10(6). This contradicts empirical regressions including stable and labile compounds. As expected, levels of labile substances vary widely around a tentative indication derived from the model. Transformation and accumulation of labile substances remains highly specific for the chemical and organism concerned but depends weakly on the octanol-water partition ratio K(ow). Several possibilities for additional refinement are identified. PMID- 17727916 TI - Carnivore tooth-marks, microbial bioerosion, and the invalidation of Dominguez Rodrigo and Barba's (2006) test of Oldowan hominin scavenging behavior. PMID- 17727917 TI - Short term effects of air pollution on hospitalizations for cardiovascular diseases in eight French cities: the PSAS program. AB - INTRODUCTION: Short term associations between air pollution indicators and hospitalizations for cardiovascular diseases have been suggested by epidemiological and clinical studies. The present study aims at estimating the association between particles with diameter <10 microm (PM(10)), nitrogen dioxide (NO(2)) and ozone and hospitalizations for cardiovascular diseases in eight French cities during the 1998-2003 period. METHODS: The daily number of hospitalizations in each city was extracted from the French hospital information system (PMSI) for cardiovascular diseases, cardiac diseases, ischemic heart diseases and stroke. Excess relative risks (ERRs) of hospitalization associated with a 10 microg/m(3) increase in pollutant levels were estimated in each city by fitting a Poisson regression model, controlling for well-known confounding factors and temporal trends. City-specific results were then combined by inverse variance weighting. RESULTS: Daily number of hospitalizations for cardiovascular diseases was associated with PM(10) levels (for a 10 microg/m(3) increase, ERR=0.8%, 95% CI: [0.2, 1.5]), with NO(2) (1.1%, [0.6, 1.6]) but not with ozone (0.1% [-0.2%, 0.5%]). Associations were stronger in people aged 65 years and over, and when only hospitalizations for ischemic heart diseases were considered. No association was found between strokes and air pollution levels. DISCUSSION: Our study suggests that the ambient levels of air pollutants currently experienced in the eight French cities, which are close to European air quality guidelines, are yet linked to a short term increase of hospitalizations for cardiovascular diseases. These results are consistent with epidemiological and toxicological data on the cardiovascular effects of air pollution. PMID- 17727918 TI - Effects of food availability on the acute and chronic toxicity of the insecticide methomyl to Daphnia spp. AB - The widespread increase of pesticides application in crops threats vicinal freshwater lentic ecosystems, frequently leading to their contamination. Due to their position in the aquatic food web, the responses to these pesticide inputs of freshwater filter-feeding zooplankters, as daphnids, provide relevant information the general risk to the ecosystem of xenobiotics. Moreover, cladoceran grazers often face fluctuations in food availability due to the phytoplankton dynamics in lentic water bodies, and food acquisition naturally conditions their fitness. In this study, the responses of Daphnia magna, and of three genotypes within the Daphnia longispina complex, to acute and chronic exposures of methomyl, were assessed. In addition, we focused on whether the food level can model the Daphnia life-history responses to the insecticide. Results showed that methomyl was acutely and chronically toxic to both D. magna and the D. cf longispina populations at very low concentrations, and remarkable differences in sensitivity were noticed when comparing the responses to the toxic among taxa/genotypes. Furthermore, food availability conditioned the overall fitness of the species although not interacting specifically on the response to the toxicant stress. PMID- 17727919 TI - Oxidative stress risk analysis for exposure to diesel exhaust particle-induced reactive oxygen species. AB - We constructed a probabilistic risk-based framework to assess the human oxidative stress (OS) risk from diesel exhaust particle (DEP)-induced reactive oxygen species. A human respiratory tract model was used to estimate DEP concentration and cumulative doses in lung regions for three occupational groupings (driver, homeworker and student) in northern, central, and southern Taiwan. Dose-response profiles were reconstructed in terms of the specific ratio of the reduced and oxidized forms of glutathione (GSH/GSSG ratio) for the human macrophage cell (THP 1) and human bronchial epithelial cell (BEAS-2B). The highest estimated median daily cumulative dose of DEP with 95% CI was for driver in northern Taiwan (DEP(2.5): 0.716 (0.443-1.197) mg and DEP(0.18): 0.584 (0.417-0.822) mg), significantly higher than that of the other settings. The driver in northern Taiwan setting had the highest cumulative dose-response calculated over a 2-year exposure period: 0.57 (0.41-0.76) and 0.70 (0.53-0.87) for DEP(2.5) and 0.40 (0.25-0.70) and 0.47 (0.34-0.80) for DEP(0.18), respectively, in THP-1 and BEAS 2B cells. Our results implicate that potential risks of OS from above-critical exposure to DEP(2.5) in all settings are found, whereas from DEP(0.18) in the driver in northern Taiwan setting is also alarming. PMID- 17727920 TI - Cancer risk assessment from trihalomethanes in drinking water. AB - This study intends to calculate the lifetime cancer risks resulting from intakes of trihalomethanes (THMs) in drinking water based on the presence of each THM species. The slope factors for each THM species are used, combined with exposure model and Monte Carlo simulations, to calculate the cancer risks with consideration of different exposure routes (oral ingestion, inhalation and dermal absorption). The results revealed that the highest risk comes from the inhalation exposure to chloroform during showers, which also dominates the total risk associated with chloroform exposure. For dichlorobromomethane and chlorodibromomethane, inhalation exposure also plays an important role for total risks; however, contribution from the oral consumption cannot be ignored for these two compounds. Bromoform contributes the least cancer risk among the four THM species, with a risk factor two orders of magnitude smaller than the other three THM species. For all of the four THM species, exposure from dermal absorption is not significant when compared with oral ingestion and inhalation exposures. This study also uses the THMs data collected from Taiwan to calculate the cancer risks associated with THM exposures in different areas of Taiwan. Due to the variations of the THMs compositions, it is observed that higher concentrations of total THMs do not necessarily lead to higher cancer risks. Areas with higher bromide concentration in raw water and often with higher total THM concentration may actually give lower cancer risk if the THMs formed shift to bromoform. However, this also leads to the violation of THM standards since bromoform has much higher molecular weight than chloroform. Based on the results of the cancer risks calculated from each THM species, the regulatory issue of the THMs was also discussed. PMID- 17727921 TI - A lead isotopic assessment of tree bark as a biomonitor of contemporary atmospheric lead. AB - The outermost bark layer of trees, predominantly Scots pine (Pinus sylvestris), was sampled at 82 non-urban locations from six arbitrarily designated areas (Northwest, Northeast, Central Highlands, Central and East, Central and Southwest, Southeast), throughout Scotland during 2002-2003 and analysed for lead concentration and stable lead isotopes by flame atomic absorption spectrometry (AAS) and inductively coupled plasma-mass spectrometry (ICP-MS), respectively. The mean lead concentration and mean (206)Pb/(207)Pb ratio (+/-1 standard deviation, SD) for bark samples from the areas were as follows: Northwest (8.0 mg kg(-1), 1.121+/-0.014, n=17), Northeast (8.9 mg kg(-1), 1.117+/-0.012, n=12), Central Highlands (11.3 mg kg(-1), 1.130+/-0.010, n=11), Central and East (35.3 mg kg(-1), 1.120+/-0.007, n=10), Central and Southwest (20.6 mg kg(-1), 1.125+/ 0.018, n=22) and Southeast (34.4 mg kg(-1), 1.120+/-0.005, n=10), with an overall mean lead concentration of 18.5 mg kg(-1) (range 0.6-146 mg kg(-1), median 8.4 mg kg(-1)) and an overall mean (206)Pb/(207)Pb ratio of 1.122+/-0.014 (range 1.089 1.168, median 1.122). The overall mean (206)Pb/(207)Pb ratio for bark was therefore significantly lower (p<0.01, t test) than the mean atmospheric (206)Pb/(207)Pb ratio of 1.154+/-0.006 (range 1.144-1.167, n=50) and 1.154+/ 0.010 (range 1.134-1.171, n=26) as determined in rainwater collected routinely at Glensaugh, Central Highlands, during 2002 and 2003, respectively. The bark (206)Pb/(207)Pb values, 90% of which lay between 1.10 and 1.14, were more akin to those recorded for the atmosphere (via rainwater, atmospheric particulates, moss, etc.) at various locations throughout Scotland during the 1990s, a decade over which the use of leaded petrol (mean (206)Pb/(207)Pb ratio=1.076+/-0.011) declined markedly before its complete withdrawal in 2000. This strongly suggests that the lead content and isotopic composition of tree bark from Scots pine, which reputedly sheds its outer layers every couple of years or so, reflect exposure to atmospherically deposited lead (in the atmosphere or soil) over a much longer time period than just the previous 2-3 years of exposure to contemporary atmospheric lead. The possible influence of soil lead upon tree bark through external attachment was not observed in a comparative sub-set study of 27 paired bark (mean (206)Pb/(207)Pb ratio=1.122+/-0.016) and surface (0-2 cm) soil (mean (206)Pb/(207)Pb ratio=1.145+/-0.022) samples, in only six cases (i.e. 22%) of which did the corresponding (206)Pb/(207)Pb ratios agree within +/-2 SD. Likewise, bark (206)Pb/(207)Pb values exhibited no discernible trend with distance from the nearest road, with similar average values for 0-20 m (1.123+/ 0.015, n=34) and 20-700 m (1.122+/-0.012, n=48), although the corresponding mean (and median) lead concentration of 23.5 (10) mg kg(-1) vs. 14.9 (7.5) mg kg(-1) was slightly higher for the former. The influence of airborne dusts from waste deposits related to former mining/smelting of Wanlockhead/Leadhills lead ores ((206)Pb/(207)Pb=1.170+/-0.003) could be seen, however, in the sycamore bark lead concentrations of up to 3050 mg kg(-1) and (206)Pb/(207)Pb ratios (1.168-1.171) observed at a distance of 0.5 km away. PMID- 17727922 TI - The anti-inflammatory effects of heparin and related compounds. AB - Heparin is a glycosaminoglycan well known for its anticoagulant properties. In addition, heparin possesses anti-inflammatory effects. Although the mechanisms responsible for the anticoagulant effects of heparin are well understood, those underlying its anti-inflammatory effects are not. This review presents some of the evidence from clinical and animal studies supporting an anti-inflammatory role for heparin and heparin-related derivatives. Potential mechanisms by which heparin can exert its anti-inflammatory effects are discussed. The clinical use of heparin as an anti-inflammatory agent has been held back by the fear of bleeding. Development of nonanticoagulant heparins or heparin derivatives should mitigate this concern. PMID- 17727924 TI - Biochemical prognostic factors and risk of relapses in patients with cervical cancer. AB - No validated tumor marker is currently available for the management of patients with cervical cancer. However, some tumor-associated antigens have been measured in the sera from patients with this malignancy and have been related to the clinical course of disease. Squamous cell carcinoma antigen (SCC) is more sensitive than CYFRA 21-1 for squamous cell cervical cancer. Serum SCC levels are elevated in 28-88% of patients with this malignancy, and correlate with tumor stage, tumor size, cervical stromal invasion, lymph-vascular space involvement, and lymph node status. Some authors reported that pre-treatment serum SCC has no prognostic value, whereas others found that it is related to disease-free survival and/or overall survival at univariate analysis or at multivariate analysis. Serial SCC measurements correlate with tumor response to radiotherapy and/or chemotherapy and the clinical outcome of patients. Increasing serum SCC can precede the clinical diagnosis of relapse in 46-92% of cases, with a median lead time ranging from 2 to 8 months. According to some authors serum SCC assay during the follow-up does not improve the cure rate of patients who will ultimately develop a recurrence. However, it has been recently reported that the performance of a PET in asymptomatic patients with serum SCC elevation can sometimes allow an earlier diagnosis of relapse with a survival benefit. Serum CA 125 levels are raised in 20-75% of patients with cervical adenocarcinoma, and reflect tumor stage, tumor size, histological grade, cervical stromal invasion, lymph-vascular space involvement, and lymph node status. Pre-treatment CA 125 levels appear to have a prognostic value, and rising serum CA 125 may precede or be coincident with the clinical diagnosis of recurrent cervical adenocarcinoma. PMID- 17727923 TI - Effect of adenosine A2 receptor stimulation on platelet activation-aggregation: differences between canine and human models. AB - INTRODUCTION: Adenosine A(2) agonists improve arterial patency in experimental models of recurrent thrombosis, an effect purportedly triggered by stimulation of platelet A(2) receptors and subsequent down-regulation of platelet function. However: (i) there is no direct evidence to substantiate this premise; and (ii) given the recognized differences among species in platelet signaling, it is possible that the mechanisms of A(2) receptor stimulation may be model-dependent. Accordingly, we applied an integrated in vivo and in vitro approach, using both canine and human models, to test the hypothesis that the anti-thrombotic effects of A(2) agonist treatment are due in part to inhibition of platelet activation. METHODS: In Protocol 1, recurrent coronary thrombosis was triggered in anesthetized dogs by application of a stenosis at a site of arterial injury. Coronary patency and flow cytometric indices of platelet activation (P-selectin expression; formation of heterotypic aggregates) were compared in dogs pre treated with the A(2) agonist CGS 21680 versus controls. In Protocols 2 and 3, blood samples were obtained from dogs and human volunteers. In vitro aggregation and platelet activation (assessed by impedance aggregometry and flow cytometry, respectively) were quantified in paired aliquots pre-incubated with CGS versus vehicle. RESULTS: In the canine models, CGS improved in vivo coronary patency and attenuated in vitro aggregation but, contrary to our hypothesis, did not evoke a down-regulation in platelet activation. In contrast, in human blood samples, CGS attenuated both in vitro aggregation and flow cytometric markers of platelet activation-aggregation. CONCLUSION: The mechanisms contributing to the anti thrombotic effect of A(2) agonist treatment are species-dependent: adenosine A(2) receptor stimulation inhibits platelet activation in human, but not canine, models. PMID- 17727925 TI - The importance of statistics in an advancement of cancer research. PMID- 17727926 TI - Carcinosarcoma of the uterine cervix: case report and discussion. AB - BACKGROUND: Cervical carcinosarcomas are rare neoplasms; optimal treatment is unclear. CASE 1: A 42-year-old woman underwent abdominal hysterectomy because of bleeding, anaemia and uterine fibromatosis. Histology showed a homologous carcinosarcoma of the cervix. Laparoscopic re-staging (pelvic lymphadenectomy, bilateral salpingo-oophorectomy) was negative for neoplasia. Adjuvant chemotherapy with ifosfamide and cisplatin was performed. At 48 months of follow up, the patient is NED. CASE 2: A 74-year-old woman reporting vaginal bleeding, with carcinosarcoma on the cervical biopsy, underwent radical hysterectomy, bilateral salpingo-oophorectomy, pelvic and paraortic lymphadenectomy. Histology confirmed a homologous carcinosarcoma of the cervix, stage IIb. Whole-pelvis irradiation and brachytherapy were carried out. Nine months later, the patient developed systemic recurrence and died of disease. Aggressive primary therapy can result in cure of early-stage cervical carcinosarcomas. Extracervical disease is associated with a poor prognosis. PMID- 17727927 TI - An update in neoadjuvant chemotherapy in cervical cancer. AB - More than two decades have passed since neoadjuvant chemotherapy has been introduced in the clinical practice. After several pilot studies, randomized trials and meta-analysis have confirmed the validity of this therapeutic strategy and in particular of neoadjuvant chemotherapy followed by radical surgery. Several open questions still remain unanswered and in particular no standard drug regiment is unanimously accepted. In this paper we describe how this treatment has evolved since its original introduction in the early eighties and describe possible drug regimens with their supporting evidence that can be adopted by physicians worldwide. PMID- 17727929 TI - Which role for pre-treatment laparoscopic staging? AB - OBJECTIVE: To investigate in cervical cancer patients the impact of pre-treatment laparoscopic staging on treatment plan and disease free survival. METHODS: A review of the present literature has been performed and data have been compared to results obtained in a large series of patients not surgically staged. RESULTS: Among 134 abstracts resulting from Medline research, 13 were deemed potentially relevant to the study questions. The presence of intraperitoneal diffusion of disease can be recognized in locally advanced cervical cancer patients (LACC) in a percentage ranging between 1.9% and 29%. The rate of aortic positive nodes in clinically negative LACC patients cases has been reported between 11% and 25%, by laparoscopy. In our Division, 152 LACC patients have been treated between October 1997 and February 2007. None of the patients has been submitted to pre-treatment laparoscopic staging, whereas in all cases a pre-operative MRI has been performed. With a median follow-up 28.0 months (range 3-126 months), 31 recurrences have been observed. The 5-year DFS has been 83% and OS 90%. Although only a retrospective analysis can be carried out, such result well compares to cases surgically staged. CONCLUSIONS: Pre-treatment surgical staging can identify positive nodes in LACC patients considered clinically negative, and recognize intraperitoneal disease, thus making the physician tailor the treatment on the bases of histopathological result. Moreover, it offers the potential advantage of debulking of macroscopically positive nodes, and to transpose the ovary outside the radiation. However, the positive impact on DFS has still to be demonstrated. PMID- 17727930 TI - The role of FDG-PET/CT imaging after radiation therapy. PMID- 17727928 TI - Epidemiologic modeling of cervical dysplasia with molecular and cytopathological markers. AB - OBJECTIVES: Conventional cervical screening is insufficient at identifying patients who are likely to progress from cervical dysplasia to carcinoma. Traditional epidemiologic studies have identified potential factors to aid in the discrimination between those lesions likely to progress from those likely to regress; however, there is still much to be learned. To examine the role of traditional epidemiologic factors in conjunction with molecular markers of human papillomavirus activity, we studied a group of women attending colposcopy clinics in Houston, TX, and Vancouver, BC, between October 2000 and July 2003. METHODS: Quantitative real-time PCR was used to measure mRNA expression of the human papillomavirus E7 gene, and quantitative cytology was used to gather information about the DNA index and chromatin features of the cells from these women. Logistic regression was used to establish predictor variables for histologic grade based on the epidemiologic risk factors and the molecular markers. RESULTS: The most predictive factors were mRNA level, DNA index, parity, and age. The ROC curve for the individual logits indicated excellent discrimination. CONCLUSION: In accordance with other authors, these results suggest that molecular markers of the malignant process should be included in analyses looking to predict the progression potential of cervical lesions. PMID- 17727931 TI - Do we need a new classification for radical hysterectomy? Insights in surgical anatomy and local tumor spread from human embryology. AB - OBJECTIVE: Current surgical treatment of cervical carcinoma is based on the assumption of undirected intra- and transcervical local tumor propagation and is executed by tailored excision of the paracervical tissues. We have recently demonstrated that cervical carcinoma spreads for extended phases during its malignant progression within the permissive compartment of the Mullerian morphogenetic unit (Lancet Oncol 2005;6:751-56) and proposed Mullerian compartment resection as the new principle for surgical treatment of cervical cancer. Do we need a new classification of radical hysterectomy? METHODS: The therapeutic index of the surgical treatment of cervical carcinoma FIGO stages IB1 IIB by extirpation of the Mullerian compartment through total mesometrial resection (TMMR) without adjuvant radiation is evaluated by an ongoing controlled prospective trial at the University of Leipzig. RESULTS: From 7/1998 to 12/2006, 163 patients with cervical carcinoma, FIGO stages IB1 (n=94), IB2 (n=21), IIA (n=14) and IIB (n=34) have been treated with TMMR and nerve-sparing therapeutic lymph node dissection. Twenty-five patients received (neo)adjuvant chemotherapy. No patient underwent adjuvant radiotherapy although 95 patients (58%) would have needed this additional modality in case of conventional radical hysterectomy because of their high-risk histopathological tumor features. At a median follow up time of 45 months (3-104 months), recurrence-free and disease-specific overall survival is 93% and 96%. Maximum treatment-related morbidity according to the Franco-Italian score has been grade 2 in 12 patients (8%). CONCLUSIONS: The developmental view of local tumor spread and surgical anatomy holds a great promise for improving the therapeutic index of surgical cervical cancer therapy and challenges both the classification of radical hysterectomy based on tailored paracervical resection and the indication for adjuvant radiation. PMID- 17727933 TI - Aortic lymphadenectomy in cervical cancer: anatomy, classification and technique. AB - Lymphatics are the main pathway of dissemination for gynaecologic malignancies and in particular those with preferential regional spread, so the evaluation of lymph node status has an important role in diagnosis, prognosis and treatment of patients with gynaecologic cancer. Hence, gynecologic oncologist must be familiar with lymphatic anatomy and the ability to perform a systematic retroperitoneal pelvic and aortic lymph node dissection is an important skill in their surgical armamentarium. This review will focus on the performance of systematic aortic lymphadenectomy in cervical cancer. PMID- 17727932 TI - Nerve-sparing radical hysterectomy in cervical cancer: evolution of concepts. AB - OBJECTIVES: This paper reviews the evolution of concepts concerning the nerve sparing radical hysterectomy (NSRH) in cervical cancer. METHODS: Research studies published between 1991 and 2006 were reviewed. RESULTS: Significant progress has been made in understanding the neuroanatomy and the neurophysiology of autonomic pelvic plexus. The ideal surgical management of cervical cancer patients should be tailored on the basis of prognostic factors and quality of life. Within the discussion concerning the optimal level of radicality of hysterectomy, which is still controversial, the new concept of NSRH has to be considered in order to reduce morbidity without compromising the oncological disease control. Surgical strategies have been developed to spare the autonomic functions with promising results. CONCLUSIONS: To date, there is a growing body of data about NSRH in cervical cancer. However, there is not yet a consensus concerning to which part of uterine support ligaments a NS approach should be directed. PMID- 17727934 TI - Conservative approaches in early stages of cervical cancer. AB - Several authors have proposed the use of a less aggressive surgery (i.e. conization, trachelectomy plus laparoscopic lymphadenectomy, modified or type 2 radical hysterectomy) for patients affected by early stages invasive cervical carcinoma. Tumor size and pelvic nodal status are parameters that must be evaluated to better select a patient's population suitable of a less aggressive surgery, with the aim of sparing morbidity without jeopardizing cancer cure. PMID- 17727935 TI - Chemo-conization in early cervical cancer. AB - OBJECTIVES: The aim of the present study is to support the safety and feasibility of chemo-conization for early-stage cervical tumor in young patients wishing to preserve their fertility. METHODS: Between October 2004 and November 2006, eleven patients were scheduled for conservative treatment. Subjects were selected for this treatment on the basis of favorable cervical tumors (<3 cm) and a desire to maintain fertility. All patients underwent neoadjuvant chemotherapy followed by conization or conization alone with pelvic lymphadenectomy. Obstetrical and oncologic outcomes were evaluated. RESULTS AND CONCLUSIONS: The mean age of the eleven patients was 32 (range: 24-41), Figo Stage was IB1 in 8 cases and 3 cases were Stage IA2. Histological findings were squamous cell carcinoma in 5 patients and adenocarcinoma in 6 patients. Two patients were treated with TEP regimen every 3 weeks for three courses, while one patient had adjuvant chemotherapy with TEP. No recurrences were observed after a median follow-up of 20 months (range 7 29 months). Three pregnancies occurred during the follow-up period. Although the number is small, in selected patients this conservative approach seems to be feasible to cure early-stage cervical cancer therefore maintaining fertility. PMID- 17727936 TI - Preoperative concomitant chemoradiotherapy in locally advanced cervical cancer: safety, outcome, and prognostic measures. AB - OBJECTIVES: To evaluate the morbidity, and the therapeutic value of surgery after chemoradiation in a large series of locally advanced cervical cancers (LACC). The prognostic role of different clinico-pathological factors has been also evaluated. METHODS: Between October 1997 and October 2006, 161 LACC patients were treated at both the Gynecologic Oncology Units of the Catholic University of Rome and Campobasso. Radiotherapy was administered to the whole pelvic region in combination with cisplatin and 5-fluorouracil. Radical surgery was performed 5-6 weeks after the end of the treatment. RESULTS: A clinical complete/partial response was observed in 153 patients and radical surgery was performed in 152 cases. The overall rate of surgical complications was 33% with 15 (10%) patients experiencing severe toxicities. At pathological examination 111 of 152 patients (73%) showed absent/microscopic residual disease. With a median follow-up of 28 months, the 5-year disease free-survival (DFS) was 83% and the 5-year overall survival (OS) 90%. Advanced FIGO (Federation Internationale de Gynecolgie et d'Obstetrique) stage, pathological response and lymph node involvement were found significantly associated with clinical outcome. CONCLUSIONS: We confirmed in a larger series the safety and efficacy of this multimodal approach in the treatment of LACC. The pathological assessment of response can allow not only a tailored surgery in selected patients, but also the identification of patients with higher risk of recurrence to be submitted to adjuvant therapies. PMID- 17727937 TI - Impedance measurements for cervical cancer diagnosis. AB - This article discusses using impedance measurements of body tissue in a diagnostic device. It then reviews the theory behind using these measurements to separate normal from diseased tissue. A small amount of time is devoted to discussing the meaning of sensitivity, specificity, and the receiver operating characteristic (ROC) curve, and their meanings. It also discusses the prospects of some new clinical devices using impedance measurements. One of the devices it focuses on is the TruScreen probe made by the Australian firm, Polartechnics. PMID- 17727939 TI - ASC-US diagnosis and triage. PMID- 17727938 TI - Intraoperative techniques and tumor margin status--room for improvement for cervical cancer patients of childbearing age. AB - OBJECTIVE: Inadequate tumor margin status in cervical cancer and pre-cancer patients is associated with repeat procedures and an increased risk of recurrence and progression. This review will outline information regarding the current treatment options for women who wish to maintain fertility, the methods currently used in practice to evaluate tumor margin involvement, and a look at potential solutions to this critical issue. METHOD: We performed a PUBMED literature search of relevant research articles pertaining to tumor margin evaluation for multiple cancers, current treatment options for patients of cervical dysplasia and the effects of those treatments on fertility. RESULTS: Previous studies have correlated cancer recurrence and progression to obtaining clear margins upon resection. The most common need to obtain clear margins with respect to conservative treatment in patients with cervical neoplasia occurs with women who wish to preserve fertility. However, current detection methods are limited and current treatments present additional fertility concerns. CONCLUSION: In order to provide the best care for patients wishing to retain fertility post-treatment for cervical dysplasia, a superior option for detecting tumor margins accurately at the microscopic scale must be further explored. PMID- 17727940 TI - The contribution of new imaging techniques in staging cervical cancer. PMID- 17727942 TI - A comparative study of the bioactivity of three materials for dental applications. AB - OBJECTIVES: The aim of this work was to investigate the in vitro bioactivity of two different experimental dental luting cement formulations based on calcium aluminate (CA) in comparison with glass ionomer cement (GIC). One of the CA-based formulations was a hybrid between CA and GIC. METHODS: Samples were submerged in phosphate buffered saline and stored at 37 degrees C for four periods of time: 1 h, 1 day, 7 days and 4 weeks. After storage the samples were analyzed in order to investigate if a surface layer of hydroxyapatite had formed. The analysis techniques used included grazing incidence X-ray diffraction, scanning electron microscopy, energy dispersive spectroscopy and transmission electron microscopy. RESULTS: Both the CA-containing formulations were found to be bioactive. The highest degree of bioactivity was found on the sample with only CA as active substance. A relatively thick and totally covering layer was already formed after 24 h. On the hybrid material hydroxyapatite was found after 7 days. The GIC showed no bioactivity during the test period. SIGNIFICANCE: The utilization of a bioactive material for tooth restorations will give an opportunity for remineralization and a natural and durable seal of the tooth-material interface. Materials based on CA exhibit bioactivity. PMID- 17727941 TI - Eight-year change in body mass index and subsequent risk of cardiovascular disease among healthy non-smoking men. AB - OBJECTIVE: To determine how change in BMI over 8 years is associated with risk of subsequent cardiovascular disease (CVD) among middle aged men. METHODS: Prospective cohort study among 13,230 healthy men (aged 51.6+/-8.7 years) in the Physicians' Health Study. BMI was collected at baseline in 1982 and after 8 years, at which time follow-up began. Subsequent CVD events were collected and confirmed through March 31, 2005. Cox proportional hazards models evaluated BMI at 8 years and risk of CVD, 8-year change in BMI and risk of CVD, and whether change in BMI added prognostic information after the consideration of BMI at 8 years. RESULTS: 1308 major CVD events occurred over 13.5 years. A higher BMI at year 8 was associated with an increased risk of CVD. Compared to a stable BMI (+/ 0.5 kg/m(2)), a 0.5-2.0 kg/m(2) increase had a multivariable-adjusted RR of 1.00 (0.86-1.16). A >/=2.0 kg/m(2) increase had a multivariable-adjusted RR of 1.39 (1.16-1.68), however further adjustment for BMI reduced the RR to 1.00 (0.81 1.23). A decrease in BMI had a multivariable RR of 1.23 (1.07-1.42) which was unaffected by adjustment for BMI at 8 years. CONCLUSION: A higher BMI and a rising BMI were both associated with an increased risk of CVD, however an increasing BMI did not add prognostic information once current BMI was considered. In contrast, a declining BMI was associated with an increased risk of CVD independent of current BMI. PMID- 17727943 TI - Clinical performance and wear characteristics of veneered lithia-disilicate-based ceramic crowns. AB - OBJECTIVES: The objectives of this study were to characterize the clinical performance and wear characteristics of lithia-disilicate-based ceramic crowns. METHODS: Thirty posterior crowns were made using the heat-pressing technique and lithia-disilicate-based core ceramic. Subjects were recalled annually. The quality of crowns and adjacent gingival tissues were examined using nine criteria for acceptability. All crowns were examined and ranked from 4 (Excellent) to 1 (Unacceptable) for each criterion. Impressions were made for replica models at each appointment. Wear characteristics of dental ceramic and enamel were obtained by comparing the surface of the original model with the follow-up model using a laser scanner. RESULTS: Twenty-nine subjects returned for the 1-year recall examination. The maximum clenching force for the 30 subjects ranged from 125 to 815 N. All clinical criteria were ranked good to excellent at the 1-year recall exam and no fractures were observed. The mean occlusal wear volumes for the ceramic crowns after 1 year were 0.19 (0.065)mm3 for premolar sites and 0.34 (0.08)mm3 for molar sites. The mean occlusal wear volumes of opposing enamel after 1 year were 0.21 (0.06)mm3 for premolar teeth and 0.50 (0.22)mm3 for molar teeth. The mean occlusal wear volume of ceramic molar crowns was significantly lower than the volume of enamel wear of the opposing teeth (por=60 years, unfavorable cytogenetics, initial WBC count and secondary AML significantly influenced survival (p<0.001, p<0.001, p=0.035, and p=0.010, respectively). OS was similar for AAs and non-AA non-Cs compared to Cs (HR=1.12, 95% CI=.61-2.07, p=.71, and HR=0.87, CI=0.21-3.62, p=.84, respectively). Neither DTC (HR=1.00, 95%CI=0.98-1.01, p=.96 per 20 mile increment) nor SES (HR=1.02, 95%CI=0.92-1.13, p=.77 per USD10,000 annual income increase) had an impact on OS. CONCLUSION: Unlike with many solid tumors, SES and DTC are not predictive of outcome in AML patients. PMID- 17727947 TI - Induction of late graft-versus-host disease in a patient post-allogeneic stem cell transplantation by progesterone in conjunction with donor lymphocyte infusion. AB - Patients after stem cell transplantation (SCT), often develop graft-versus-host disease (GVHD) which, although potentially dangerous, is associated with the beneficial graft-versus-leukemia (GVL) effect. Where there is high risk of disease recurrence, donor lymphocyte infusions (DLI) are given to provide long term disease control. We present a patient treated with DLI 4 years post-SCT, who developed acute GVHD after administration of progesterone to induce menstruation. This rare allergic reaction warrants further investigation. PMID- 17727948 TI - Reduction of growth and haemolymph Ca levels in the freshwater snail Lymnaea stagnalis chronically exposed to cobalt. AB - The ecological risk assessment and the development of water-quality criteria for Co are currently still hampered by insufficient knowledge about the toxicity of Co to freshwater organisms. A relevant group of organisms, for which no toxicity data with Co are available, is the class of the herbivorous pulmonate freshwater snails, which fulfil a pivotal role in the consumption and decomposition of aquatic plants and epihyton. We measured the growth rate of the pond snail Lymnaea stagnalis chronically exposed for 28 days to a series of Co concentrations. The no observed effect concentration (NOEC) and the lowest observed effect concentration (LOEC) for growth rate were 26 and 79 microg Co/L, respectively. Growth rate of snails exposed to 79 microg Co/L and higher concentrations was more impaired in the final 2 weeks of exposure than in the first 2 weeks of exposure. The reduced growth rate at 79 microg Co/L was accompanied by a reduced concentration of Ca in the haemolymph at the end of the exposure. Possible mechanisms of toxicity of Co to snail growth were suggested to be an impairment of Ca uptake and homeostasis and/or feeding inhibition. Although additional research is needed to investigate the relative importance of these mechanisms, as well as the interrelatedness between them, the toxicity data currently presented can assist in risk assessment and water-quality criteria development. PMID- 17727949 TI - Neurocutaneous melanosis in a newborn with giant congenital melanocytic nevus. AB - Neurocutaneous melanosis (NCM) is known as a rare phakomatose characterised by large or numerous pigmented congenital nevi associated with leptomeninges melanin containing deposits. We report a case of a newborn presenting at birth with a giant nevus covering about 40% of the total body surface. MRI showed T1 hyperintensities in the right amygdala and predominantly in the cerebellum corresponding to melanocytic cells. PMID- 17727950 TI - Unexpected high PCB and total DDT levels in the breeding population of red kite (Milvus milvus) from Donana National Park, south-western Spain. AB - This study provides information on the current status of contamination by organochlorines (DDTs, PCBs, PCDDs and PCDFs) in the declining red kite (Milvus milvus L.) population breeding in the Donana National Park (DNP), south-western Spain. Analyses were performed in addled eggs collected between 1999 and 2001. DDE concentrations ranged from 0.1 to 33.5 microg/g ww, representing more than 86% of the total DDTs. Of the samples studied, 50% showed DDE levels above those associated with reproductive impairment in other raptor species. Concentrations of ortho PCBs (average 36.8 microg/g ww+/-37.7) in 50% of the eggs were much higher than levels reported to cause reduced hatching success, embryo mortality, and deformities in birds (>20 microg/g ww). It is remarkable that average ortho PCB and DDE concentrations showed an increase of one order of magnitude compared to previous data for the species during the 80s. Total PCDD/Fs showed levels in the low pg/g range (7.2-42 pg/g ww), having PCDDs and PCDFs similar contributions in most samples. Total mean TEQs were 238 pg/g (ww), being the range 7.02-667 pg/g (ww). Spatial variation within DNP was observed for PCBs, DDTs, as well as for TEQs. Since some eggs exceeded the NOEL (67%) and LOEL (33%) reported for other raptor species, we would expect the red kite to experience detrimental effects to dioxin-like toxicity. Our results suggest that organochlorine contaminants should be regarded as an element of concern in the population under study, in addition to other conservation problems already reported. Further investigations should be undertaken to identify potential sources of these chemicals in DNP, and to find out if organochlorine contamination is present in other predator species in the area, as well as their potential health effects on individuals and/or populations. PMID- 17727951 TI - 'Incongruous juxtapositions': the chimaera and Mrs McK. AB - A century ago, the German botanist Hans Winkler (best known for coining the term 'genome') accomplished two novel transplantations. First, he produced a single plant that grafted together two completely disparate species: tomato and nightshade. Second, he chose the descriptive word 'chimaera' to name his innovation, transplanting the term from mythology to biology. This paper features Mrs McK, the first human chimera, and thus follows the term from botany to clinical medicine. Her remarkable story, pieced together from the notes, drafts and correspondence of Robert Race and his colleagues at the MRC Blood Group Unit, draws attention to the significance of names and naming. PMID- 17727952 TI - Identification and characterization of a new interleukin-8 receptor in bovine species. AB - Mastitis is an inflammation of the mammary gland, most of the time caused by invading pathogens. Phagocytosis by neutrophils is a crucial defense of the mammary gland and the prompt recruitment of these phagocytes from blood to milk compartments is essential for the outcome of the infection. ELR+ CXC chemokines, ligands of the two interleukin-8 receptors (IL-8R), CXCR1 and CXCR2, are likely to be involved in the initiation of the inflammatory response and also in the migration of neutrophils. Recently, the polymorphism of bovine CXCR2 has been associated with resistance to mastitis. However, as the bovine IL-8R are not functionally defined, their contribution to the recruitment of neutrophils remains undetermined. In this study, the RNA ligase-mediated (RLM)-RACE method was used to clone a novel bovine interleukin-8 receptor (nIL-8R) of the bovine species. We showed that both bovine IL-8R (nIL-8R and the published CXCR2) are functional since bovine IL-8 induced migration of HEK-293 cells expressing either IL-8R. In addition, comparisons of full-length sequences suggested that the published CXCR2 sequence was improperly annotated and that the sequences of the nIL-8R and the published CXCR2 are homologous to human CXCR2 and CXCR1, respectively. This was confirmed by binding assays with labeled IL-8 and GRO-beta and calcium (Ca) flux responses of transfected cells. Moreover, the C-terminal of both bovine IL-8R showed 100% identity, whereas they differ in most other species, suggesting that the two bovine IL-8R initiate similar signal transduction. These results constitute a basis to improve our understanding of the molecular mechanisms implicated in the recruitment of bovine neutrophils. PMID- 17727953 TI - The interferon response is involved in nervous necrosis virus acute and persistent infection in zebrafish infection model. AB - Betanodavirus, a small positive-sense bipartite RNA virus notoriously affecting marine aquaculture worldwide has been extensively studied in vitro. However, impending studies in elucidating virus-host interactions have been limiting due to the lack of appropriate animal disease models. Therefore, in this study, we have attempted to successfully establish NNV infection in zebrafish (Danio rerio) showing typical NNV symptoms and which could potentially serve as an in vivo model for studying virus pathogenesis. Zebrafish being already a powerful research tool in developmental biology and having its genome completely sequenced by the end of 2007 would expedite NNV research. We have observed viral titers peaked at 3 days post-infection and histological study showing lesions in brain tissues similar to natural host infection. Further, we used this infection model to study the acute and persistence infection during NNV infection. Interestingly, RT-PCR and immunoblotting assays revealed that the acute infection in larvae and juveniles is largely due to inactive interferon response as opposed to activated innate immune response during persistent infection in adult stage. This study is the first to demonstrate NNV infection of zebrafish, which could serve as a potential animal model to study virus pathogenesis and neuron degeneration research. PMID- 17727954 TI - Oxidative stress in the hippocampus, anxiety-like behavior and decreased locomotory and exploratory activity of adult rats: effects of sub acute vitamin A supplementation at therapeutic doses. AB - Vitamin A participates in the maintenance of normal hippocampal function during embryonic and postnatal stages of the vertebrate life. Some works demonstrated that vitamin A metabolites impair learning and induce a depression-like behavior in mice, among other effects. Since vitamin A has prooxidant effects on other experimental models, we decided to investigate whether vitamin A can induce oxidative stress in the adult rat hippocampus. We analyzed the sub acute effects of therapeutic (1000 and 2500 I.U./kg) or excessive (4500 and 9000 I.U./kg) vitamin A doses on the hippocampal redox state, as well as on levels of anxiety, and locomotory and exploratory activity. Vitamin A supplementation induced lipid peroxidation, protein carbonylation, and oxidation of the protein thiol content in the rat hippocampus in all periods analyzed. Increased superoxide dismutase (SOD) activity and decreased catalase (CAT) activity were also observed, which gives rise to an imbalance in the principal cellular enzymatic antioxidant system. Then, our results show, for the first time, that vitamin A induced oxidative stress in the adult rat hippocampus, is anxiogenic, and decreases locomotion in and exploration of an open field. PMID- 17727955 TI - Infants' perception of subjective contours from apparent motion. AB - We examined infants' perception of subjective contours in Subjective-Contour-from Apparent-Motion (SCAM) stimuli [e.g., Cicerone, C. M., Hoffman, D. D., Gowdy, P. D., & Kim, J. S. (1995). The perception of color from motion. Perception & Psychophysics, 57, 761-777] using the preferential looking technique. The SCAM stimulus is composed of random dots which are assigned two different colors. Circular region assigned one color moved apparently, keeping all dots' location unchanged. In the SCAM stimulus, adults can perceive subjective color spreading and subjective contours in apparent motion (http://c-faculty.chuo-u.ac.jp/ approximately ymasa/okamura/ibd_demo.html). In the present study, we conducted two experiments by using this type of SCAM stimulus. A total of thirty-six 3-8 month-olds participated. In experiment 1, we presented two stimuli to the infants side by side: a SCAM stimulus consisting of different luminance, and a non-SCAM stimulus consisting of isoluminance dots. The results indicated that the 5-8 month-olds showed preference for the SCAM stimuli. In experiments 2 and 3, we confirmed that the infants' preference for the SCAM stimulus was not generated by the local difference and local change made by luminance of dots but by the subjective contours. These results suggest that 5-8-month-olds were able to perceive subjective contours in the SCAM stimuli. PMID- 17727957 TI - Effects of alcohol on TMS-evoked N100 responses. AB - TMS combined with simultaneous EEG is a novel brain imaging tool allowing investigation local excitability of human cortex. As alcohol acts through increasing function of A-type gamma-aminobutyric acid receptors and attenuating the function of glutaminergic NMDA-receptors-related excitation, we tested whether TMS-evoked N100 response which is thought to reflect cortical inhibitory processes, might be affected by alcohol. Ten healthy subjects ingested alcohol (0.8 g/kg) and EEG responses from 60 channels before and after alcohol ingestion were recorded after left motor-cortex stimulation. Alcohol almost abolished TMS evoked N100 response. Control experiments with a piece of plastic placed between the head and coil to exclude auditory artefacts were conducted. Alcohol effects were similar when EEG responses from control experiments were subtracted from real-TMS. Alcohol-induced decrease was similar at ipsilateral, contralateral and frontal EEG sites suggesting that alcohol may change cortico-cortical connectivity of motor cortex. Alternative explanation is that alcohol has overall suppression effect on motor cortex. N100 may provide a useful marker of neural inhibition of human cortex for drug research. PMID- 17727956 TI - Design and fabrication of multichannel cochlear implants for animal research. AB - The effectiveness of multichannel cochlear implants depends on the activation of perceptually distinct regions of the auditory nerve. Increased information transfer is possible as the number of channels and dynamic range are increased and electrical and neural interaction among channels is reduced. Human and animal studies have demonstrated that specific design features of the intracochlear electrode directly affect these performance factors. These features include the geometry, size, and orientation of the stimulating sites, proximity of the device to spiral ganglion neurons, shape and position of the insulating carrier, and the stimulation mode (monopolar, bipolar, etc.). Animal studies to directly measure the effects of changes in electrode design are currently constrained by the lack of available electrodes that model contemporary clinical devices. This report presents methods to design and fabricate species-specific customizable electrode arrays. We have successfully implanted these arrays in guinea pigs and cats for periods of up to 14 months and have conducted acute electrophysiological experiments in these animals. Modifications enabling long-term intracochlear drug infusion are also described. Studies using these scale model arrays will improve our understanding of how these devices function in human subjects and how we can best optimize future cochlear implants. PMID- 17727958 TI - Leptin in depressed women: cross-sectional and longitudinal data from an epidemiologic study. AB - BACKGROUND: There is conflicting evidence regarding levels of leptin in depression. In this study we aimed to investigate the relationship between serum leptin level and depression in a community sample of women using both cross sectional and longitudinal data. METHODS: From among 510 women aged 20-78 yr, 83 were identified with a lifetime history of major depressive disorder or dysthymia, ascertained using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition (SCID-I/NP). Serum leptin levels were measured by radioimmunoassay. Medication use and lifestyle were self-reported and body mass index (BMI) determined from measures of height and weight. RESULTS: Using multiple linear regression, serum leptin levels were greater among women with a lifetime history of depression compared to women without any history of depression, independent of BMI. Adjusted geometric mean values of serum leptin were 16.37 (95%CI 14.70-18.23) ng/mL for depressed and 14.46 (95%CI 13.79-15.16) ng/mL for non-depressed women (P=0.039). The hazard ratio (HR) for a de novo depressive disorder over five years increased 2.56-fold for each standard deviation increase in log-transformed serum leptin among non-smokers and this was not explained by differences in BMI, medications or other lifestyle factors (HR=2.56, 95%CI 1.52-4.30). No association was observed for smokers. LIMITATIONS: There is potential for unrecognised confounding, recall bias and transient changes in body composition. CONCLUSION: Women with a lifetime history of depression have elevated levels of serum leptin, and elevated serum leptin predicts subsequent development of a depressive disorder. PMID- 17727959 TI - Abnormal reactions to environmental stress in elderly persons with anxiety disorders: evidence from a population study of diurnal cortisol changes. AB - BACKGROUND: Cortisol secretion in elderly persons with anxiety disorders exposed to common stressful situations has not been evaluated. METHODS: Salivary-free cortisol levels were evaluated at 8, 15, and 22 h, in 201 elderly subjects during stressful and non-stressful days. Psychiatric symptomatology was assessed by a standardized psychiatric examination (MINI). RESULTS: Elderly subjects without psychiatric disorder showed a sustained increase in cortisol secretion several hours after the exposure to a stressful situation. In comparison, subjects with anxiety disorders showed a greater increase in cortisol secretion in the stressful situation, with lowered recuperation capacity. This effect was dose dependent as a function of anxiety co-morbidity. Persons reporting lifetime major trauma with intrusions exhibited lowered continuous basal cortisol associated with efficient recuperation capacity. Independently of psychopathology, women appeared more reactive to stressful environmental conditions. LIMITATIONS: Exclusion of institutionalized persons and benzodiazepine users may have led to sampling of less severe anxiety symptoms. CONCLUSIONS: Dysregulation of the hypothalamic-pituitary-adrenal axis was observed in elderly persons with anxiety disorders experiencing environmental stress. A common pattern of up-regulated diurnal cortisol secretion was observed in anxious subjects with lifetime and current anxiety disorder irrespective of sub-type (generalized anxiety, phobias) suggesting a stable trait and a common "core" across disorders. Elderly persons who had experienced trauma with subsequent intrusions showed a distinct pattern with down-regulated activity. PMID- 17727960 TI - Acute exercise reduces the effects of a 35% CO2 challenge in patients with panic disorder. AB - BACKGROUND: Chronic exercise has been shown to have therapeutic effects in panic disorder (PD). The mechanism of these effects is unknown. Acute exercise reduces the effect of a panic challenge in healthy volunteers. Such an effect has not yet been demonstrated in PD patients. The present study aimed at exploring the antipanic effects of acute exercise on a 35% CO2 panic provocation in treatment naive PD patients to further elucidate the mechanisms of the beneficial effects of exercise on panic. METHODS: Eighteen PD patients performed either moderate/hard exercise or very-light exercise before a 35% CO2 challenge in a randomized, between-group design. The reactivity to CO2 was assessed with the Visual Analogue Anxiety Scale and the DSM-IV Panic Symptom List. RESULTS: Panic reactions to CO2 were smaller in patients that performed moderate/hard exercise in contrast to those that performed very-light exercise. Increments in both measurements and panic rates were consistently reduced by intense exercise. LIMITATIONS: Since this study focuses on the acute effects of exercise on CO2 sensitivity in patients with PD, the results of repetitive exercise sessions on the rate of spontaneous panic attacks and overall symptoms are warranted. The small sample size and other limitations are addressed. CONCLUSIONS: Exercise reduced the panicogenic effects of a CO2 challenge. In addition to its therapeutic potential, exercise may also be useful as a laboratory maneuver with heuristic value in experimental research into the mechanisms of antipanic treatment. PMID- 17727962 TI - Analysis of the expression of immunoglobulins throughout lactation suggests two periods of immune transfer in the tammar wallaby (Macropus eugenii). AB - Marsupial young are born in an under-developed state without mature immune responses. Prior to the maturation of an immune system, marsupial young are heavily reliant upon immune factors secreted in the milk to defend them against potential microbial pathogens in the environment. In this study, we identified and characterized the immunoglobulin heavy chain constant regions, light chains, polymeric Ig receptor (pIgR), J chain, neonatal Fc receptor (alpha chain) (FcRn) and the chemokine CCL28 from the model marsupial species, the tammar wallaby (Macropus eugenii). Low levels of conservation were seen in motifs in C alpha and C gamma associated with receptor binding and or transcytosis, and this may have potential implications for functionality. We evaluated the expression of immunoglobulin genes in the tammar mammary gland throughout lactation and found that two periods of increased expression of immunoglobulin genes occur. These two periods coincide with the birth of the young, and with its first emergence from the pouch. This increased expression may represent a strategy for maternal immunological protection of the pouch young. PMID- 17727963 TI - The expression of intelectin in sheep goblet cells and upregulation by interleukin-4. AB - Upregulation of intelectin (ITLN) transcript and protein has previously been shown in intestinal nematode infections of resistant mice strains with immunolocalisation of protein to goblet cells and paneth cells. In man, intelectin expression has been shown in respiratory tract epithelium, with upregulation occurring in bronchoalveolar lavage fluid of asthmatic individuals. This study describes the expression of intelectin in the respiratory tract of sheep and the immunolocalisation to goblet cells using a novel affinity-purified chicken anti-intelectin peptide antibody. Furthermore we show that when sheep tracheal explants were cultured for 48 h+/- recombinant sheep IL-4, sheep ITLN transcripts were upregulated compared with controls. Putative roles for intelectin have included an antibacterial role and an alteration of the character of mucus. Our data suggest ITLNs may play an important role in the mucosal response in allergy and parasitic infections. PMID- 17727961 TI - Failure of low-dose recombinant human IL-2 to support the survival of virus specific CTL clones infused into severe combined immunodeficient foals: lack of correlation between in vitro activity and in vivo efficacy. AB - Although CTL are important for control of lentiviruses, including equine infectious anemia virus (EIAV), it is not known if CTL can limit lentiviral replication in the absence of CD4 help and neutralizing antibody. Adoptive transfer of EIAV-specific CTL clones into severe combined immunodeficient (SCID) foals could resolve this issue, but it is not known whether exogenous IL-2 administration is sufficient to support the engraftment and proliferation of CTL clones infused into immunodeficient horses. To address this question we adoptively transferred EIAV Rev-specific CTL clones into four EIAV-challenged SCID foals, concurrent with low-dose aldesleukin (180,000U/m2), a modified recombinant human IL-2 (rhuIL-2) product. The dose was calculated based on the specific activity on equine PBMC in vitro, and resulted in plasma concentrations considered sufficient to saturate high affinity IL-2 receptors in humans. Despite specific activity on equine PBMC that was equivalent to recombinant equine IL-2 and another form of rhuIL-2, aldesleukin did not support the engraftment and expansion of infused CTL clones, and control of viral load and clinical disease did not occur. It was concluded that survival of Rev-specific CTL clones infused into EIAV-challenged SCID foals was not enhanced by aldesleukin at the doses used in this study, and that in vitro specific activity did not correlate with in vivo efficacy. Successful adoptive immunotherapy with CTL clones in immunodeficient horses will likely require higher doses of rhuIL-2, co-infusion of CD4+ T lymphocytes, or administration of equine IL-2. PMID- 17727964 TI - Resistance and susceptibility to a protozoan parasite of cattle--gene expression differences in macrophages from different breeds of cattle. AB - Cattle infected with the tick-borne protozoan, Theileria annulata, usually undergo severe morbidity, and mortality ensues in a high proportion of animals. However, we have shown that a Bos indicus breed, the Sahiwal, which originates in a T. annulata endemic area, is more resistant to the parasite. Although Sahiwals become infected, the breed exhibits fewer clinical signs and recovers from a dose of parasite which is fatal in the Holstein B. taurus breed. The Sahiwals have a significantly lower fever response, and lower levels of parasite than the Holsteins. One unusual feature of this disease is the production of acute phase proteins (APP), indicating that the parasite induces high systemic levels of pro inflammatory cytokines. In the Holsteins there is prolonged production of the APP, alpha1-glycoprotein, which, in contrast, is only slightly elevated in the Sahiwals. As the parasite infects macrophages (mphi), our hypothesis is that the Sahiwals can control the excessive production of pro-inflammatory cytokines in response to infection, and that this control is expressed at the level of the mphi. We thus reasoned that the genes underlying the observed difference in resistance to tropical theileriosis, might be identified by investigating gene expression differences in mphi from both breeds. It is possible that relevant polymorphisms might in themselves result in gene expression differences, so initially we targeted likely candidates. However, we detected no differences in expression of the pro-inflammatory cytokines, tumour necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1beta) or IL-6, in infected mphi. As it is more likely that polymorphisms in candidate genes influence the expression of other genes involved in interrelated pathways, we undertook a more global approach. We designed a bovine mphi specific cDNA microarray, which contains representatives of 5000 different genes expressed in mphi, and investigated the transcriptional responses of mphi from both breeds in response to a variety of stimuli, including infection with T. annulata. Our results indicate that there are fundamental differences in gene expression in mphi from both breeds in the way they respond to infection, and even in their pre-infection resting state. PMID- 17727965 TI - Histological characteristics and stereological volume assessment of the ovine tonsils. AB - Tonsils form a first line of defence against foreign antigens and therefore play a key role in immunity. Since documented information about ovine tonsils is limited, a study was performed in which the morphological characteristics and the volume of lymphoid tissue present in each ovine tonsil were determined. The tonsils of five adult healthy sheep were examined histologically and the volumes were estimated using the Cavalieri method. The pharyngeal tonsil had a mean volume of 1296.1+/-205.9 mm3 and was by far the largest ovine tonsil, followed by the paired palatine tonsil with a mean volume of 715.0+/-110.5 mm3. The tonsil of the soft palate, the paired tubal and paraepiglottic tonsils and the lingual tonsil were much smaller with a mean volume of, respectively, 90.3+/-24.9 mm3, 80.1+/-24.3 mm3, 29.7+/-11.8 mm3 and 10.1+/-2.8 mm3. The folds and crypts of the pharyngeal and palatine tonsils were covered by a reticular and a non-reticular epithelium. Both tonsils were mainly composed of primary and secondary lymph follicles. The palatine tonsils contained 1-3 crypts with a few secondary infoldings. Lymphoid tissue in the tonsil of the soft palate was located at the nasopharyngeal (dorsal) side of the soft palate. The tubal tonsil was lined with a pseudostratified columnar ciliated epithelium and consisted of scattered lymphoid cells and lymph follicles. The paraepiglottic tonsil consisted of lymph follicles and aggregated lymphoid cells. Its overlying keratinized stratified squamous epithelium was folded and often heavily infiltrated by lymphocytes. The ovine lingual tonsil was not macroscopically visible and did not contain clearly distinguishable lymph follicles. It consisted of aggregations of lymphoid cells that were mainly located within the vallate lingual papillae. PMID- 17727967 TI - The cleavage of the hemagglutinin protein of H5N2 avian influenza virus in yeast. AB - Influenza viruses belonging to the Orthomyxoviridae family are enveloped viruses with segmented negative sense RNA genome surrounded by a helical symmetry shell. Influenza viruses, especially the highly pathogenic avian influenza virus (HPAI) such as H5 or H7 subtype are important pathogens for the poultry industry. Due to genetic reassortments between avian and human influenza viruses, global pandemics may emerge and the naive human immunity could not be ready for them. The full length HA-encoding gene of H5N2 AIV was inserted into a secretory pPICZalphaA vector and integrated into the genome of Pichia pastoris by heterologous recombination. The HA protein secretion into the medium was induced with methanol. Besides the expected 69kDa protein, another smaller fragment about 47kDa was recognized by an anti-AIV-HA monoclonal antibody in Western blot assay. This is the first report on the cleavage of HA(0) into HA(1) and HA(2) in the methylotrophic yeast P. pastoris. This possibly was due to digestion by proteases from P. pastoris based on the amino acid sequences at the predicted cleavage site, (326)R-X-K-R(329). With similar modifications to the eukaryotes, large quantity, proper antigenicity, and low cost, this expression system may provide a simple tool to produce HA proteins for further use in preparation of ELISA kits and subunit vaccines. PMID- 17727966 TI - Development of a novel recombinant encapsidated RNA particle: evaluation as an internal control for diagnostic RT-PCR. AB - This report describes the generation of novel encapsidated RNA particles and their evaluation as in-tube internal controls in diagnostic real-time reverse transcription PCR (rRT-PCR) assays for the detection of RNA viruses. A cassette containing sequences of 2 diagnostic primer sets for foot-and-mouth disease virus (FMDV) and a set for swine vesicular disease virus (SVDV) was engineered into a full-length cDNA clone containing the RNA-2 segment of Cowpea Mosaic Virus (CPMV). After co-inoculation with a plasmid that expressed CPMV RNA-1, recombinant virus particles were rescued from cowpea plants (Vigna unguiculata). RNA contained in these particles was amplified in diagnostic rRT-PCR assays used for detection of FMDV and SVDV. Amplification of these internal controls was used to confirm that rRT-PCR inhibitors were absent from clinical samples, thereby verifying negative assay results. The recombinant CPMVs did not reduce the analytical sensitivity of the rRT-PCRs when amplification of the insert was performed in the same tube as the diagnostic target. This system provides an attractive solution to the production of internal controls for rRT-PCR assays since CPMV grows to high yields in plants, the particles are thermostable, RNase resistant and simple purification of RNA-2 containing capsids yields a preparation which is non-infectious. PMID- 17727968 TI - Hypomobility after DOI administration can be reversed by subthalamic nucleus deep brain stimulation. AB - Intervening with serotonergic neurotransmission can have profound effects on mobility. For instance, the peripheral administration of the 5-HT(2A/C) agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI), changes the locomotor activity substantially. Locomotor activity is classically linked to the basal ganglia, in which the subthalamic nucleus (STN) plays a pivotal role. In this study, we tested the hypothesis that deep brain stimulation (DBS) of the STN modulates DOI induced hypomobility. Rats were implanted with stimulating electrodes at the level of the STN and were tested in an open field (OF) task in various conditions (stimulation on/off, in combination with DOI treatment). We found that DOI administration (i.p.) reduced the behavioural activity of the animals and that STN HFS reversed these effects. This study provides the first evidence that the therapeutic effect of STN HFS may also be mediated by a 5-HT-dependent mechanism. PMID- 17727969 TI - The effects of methamphetamine exposure during preadolescence on male and female rats in the water maze. AB - Exposure to methamphetamine early in life can have lasting effects on cognitive processes. The maturation of neurotransmitter systems targeted by methamphetamine differs by gender during childhood and preadolescence, which could lead to differential long-term effects of early drug exposure. Therefore, the current study assessed whether preadolescent exposure to methamphetamine has gender specific long-term effects on adult spatial memory in rodents. Male and female rats were given 1 daily injection of 0 or 2mg/kg methamphetamine or not handled from PD21-35 and then tested as adults (PD95) in the Morris water maze. In general, male rats performed better than female rats in the water maze task regardless of treatment group. Female rats exposed to methamphetamine from PD21 35 had shorter latencies and took more direct paths to the hidden platform compared to control females during the 4 days of acquisition training and when the hidden platform was moved each day on matching to place trials. Male rats exposed to methamphetamine swam a shorter distance to the hidden platform on the first day of acquisition training, similar to the methamphetamine exposed females. However, the methamphetamine exposed males performed more poorly compared to control males in the matching to place trials. Overall, the current study found that methamphetamine exposure during preadolescence has long-term effects on spatial memory in a gender specific manner. These findings may contribute to our general understanding of the long-term effects of psychostimulant exposure at early developmental stages. PMID- 17727970 TI - Virtual environment navigation tasks and the assessment of cognitive deficits in individuals with brain injury. AB - Navigation in real environments is often impaired by traumatic brain injury (TBI). These deficits in wayfinding appear to be due to disruption of cognitive processes underlying navigation and may in turn be due to damage to the hippocampus and frontal lobes. These wayfinding problems after TBI were investigated using a virtual simulation of a Morris Water Maze (MWM), a standard test of hippocampal function in laboratory animals. The virtual environment consisted of a large virtual arena in a very large virtual room whose walls provided views of a naturalistic landscape. Eleven community-dwelling TBI survivors and 12 comparison participants, matched for gender, age and education were tested to see if they could find a location in the arena marked by one of the following: (a) a visible platform, (b) a single proximal object, (c) a single proximal object among seven other distracter objects, or (d) distal features inside and outside the room. The proximal objects allowed participants to use egocentric (body-centered) navigational strategies that rely on relatively simple stimulus-response associations. The absence of proximal cues forced the participants to rely on distal features of the environment (room walls, landscape elements) and tested their ability to use allocentric (world-based) navigational strategies requiring cognitive mapping. Results indicated that the navigation of TBI survivors was not impaired when the proximal cues were present but was impaired when proximal cues were absent. These results provide more evidence that the navigational deficit after TBI is due to an inability to form, remember or use cognitive maps. PMID- 17727971 TI - Hemocyte responses of Manila clams, Ruditapes philippinarum, with varying parasite, Perkinsus olseni, severity to toxic-algal exposures. AB - This study assessed the possible combined effects of harmful algae and parasite infection on hemocyte and hemolymph parameters of a bivalve mollusc. Manila clams Ruditapes philippinarum, were exposed for 1 week, under controlled laboratory conditions, to bloom concentrations of two cultured dinoflagellates: Karenia selliformis, and Karenia mikimotoi, with demonstrated, sub-lethal, pathological effects upon these bivalves. Each dinoflagellate treatment was added to a basal diet of Chaetoceros neogracile; controls consisted of clams fed only C. neogracile. Hemocyte characteristics measured with flow-cytometric analyses, and agglutination titer, condition index, and prevalence and intensity of Perkinsus olseni, were assessed for individual clams before and after 3 and 6 days of microalgal exposure. Multifactor analysis of variance tests were conducted to determine possible effects of the harmful algae, time of exposure, and P. olseni intensity, as well as interactions between these three factors, upon each physiological variable measured. There was no relationship between P. olseni intensity and hemolymph measures. Both Karenia species, however, had a significant effect upon hemocyte profiles of the clams, and this effect was dependent upon duration of exposure; 3 days of exposure to the dinoflagellates generally was sufficient to resolve the effects on the clams. K. selliformis had a stronger effect than K. mikimotoi, which was intermediate between K. selliformis and clams fed the non-toxic control, C. neogracile. Total hemocyte counts increased in clams exposed to the harmful algae, while the percentage of dead hemocytes, as well as hemocyte size and complexity, decreased. Furthermore, these immunomodulating effects of K. selliformis were significantly more extreme in clams with a high parasite burden, compared with lightly infected clams. This report is, to our knowledge, the first study assessing the combined effects of harmful algae and parasite infection on a physiological function (hemocyte and hemolymph parameters) of a bivalve mollusc. These findings demonstrate that clams maintain hemocyte function when infected with P. olseni, that the clam immune system responds to harmful or toxic algal exposure, and that this response is modified by parasite infection. PMID- 17727972 TI - The estrogen receptor of the gastropod Nucella lapillus: modulation following exposure to an estrogenic effluent? AB - The molecular targets of estrogenic endocrine disrupting chemicals have been studied in detail in vertebrates. The lack of basic endocrine knowledge impairs similar approaches for invertebrates. Evidence indicates that the signalling pathways of invertebrates may also be a target of estrogenic chemicals (ECs). In fact, the exposure to effluents containing ECs has been reported to impact mollusc reproduction. Despite the reported estrogen independence of the mollusc nuclear estrogen receptor (ER), its role in EC-induced toxicity has not been investigated in vivo. Therefore, we have cloned the ER of the gastropod Nucella lapillus and evaluated the effects of a mixture of estrogenic chemicals (sewage effluent) on its expression in the ovary. Here, we show that the exposure to a raw domestic/industrial effluent, impact ER expression with a simultaneous reproductive maturation. These results highlight the need to further investigate the role of ER on the reproductive process in prosobranch gastropods and whether this signalling pathway is prone to disruption by ECs. PMID- 17727973 TI - Sulfur starvation and chromium tolerance in Scenedesmus acutus: a possible link between metal tolerance and the regulation of sulfur uptake/assimilation processes. AB - In a laboratory-selected Cr-tolerant strain of the unicellular green alga Scenedesmus acutus, the capacity to synthesize higher amounts of cysteine (Cys) and reduced glutathione (GSH) than the wild-type was demonstrated to underlie tolerance to Cd and Cr(VI). In photosynthetic organisms sulfate constitutes the main sulfur source for the biosynthesis of GSH and its precursor Cys, hence it was hypothesized that the sensitivity of the two strains to Cr(VI) could be modified after culturing in sulfate-deprived medium. Both strains were grown in the presence of different concentrations or in the absence of sulfate (sulfur starved) and then assayed for Cr(VI) tolerance in standard medium. Unstarved, sulfur-starved and sulfur-replete cells (cells maintained in standard medium after S-starvation) were analysed for Cys, GSH and sulfur content. Sulfur-starved cells showed a greater tolerance to Cr(VI) than unstarved ones. The increased tolerance was ascribable to a transient physiological change and can be considered as specifically due to sulfur deprivation, since it was lost after a 3 day culture in standard medium and was not exhibited by nitrogen-starved cells. The comparison between Cys, GSH and sulfur content in sulfur-starved and sulfur replete cells of the two strains suggests that the higher tolerance to Cr(VI) after S-starvation could depend on the up-regulation of sulfate uptake mechanisms, and that the primary reason for the higher tolerance to chromium in the selected strain could be due to greater sensitivity to the decrease in negative intracellular end-products (free Cys and GSH) leading to an earlier up regulation of sulfate assimilation processes. PMID- 17727974 TI - Is the umbo matrix of bivalve shells (Laternula elliptica) a climate archive? AB - Heavy metal accumulation into bivalve soft tissues has received increasing interest in recent years with respect to biomonitoring of environmental change including pollution. To a lesser extent, accretion of elements from the environment into bivalve hard structures (shells) has been investigated, although the importance of the shells as environmental archives has been acknowledged. Here we report element distribution within consecutive growth bands in the shells of the Antarctic soft shell clam Laternula elliptica, which is currently exposed to vast environmental change in Antarctic Peninsula coastal environments that undergo rapid climate warming. We performed a high spatial resolution analysis for Al, Fe, Mn, Cu, Pb and U in the shell umbo, by means of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Element ratios within the umbo did not resemble either the ratios in the surrounding seawater, the sedimenting material in Potter Cove, or even the Earth's crust basal composition. Mn and Cu were preferentially incorporated into the umbo. A strong decrease of element accretion with time could be related to lifetime respiration mass (R) of the animals. This indicates element accretion into the umbo and shell matrix to be largely a function of animal ecophysiology and life history, and these effects need to be considered in the context of potential usefulness of L. elliptica shells as environmental archives. PMID- 17727975 TI - Toxicity of titanium dioxide nanoparticles to rainbow trout (Oncorhynchus mykiss): gill injury, oxidative stress, and other physiological effects. AB - Mammalian and in vitro studies have raised concerns about the toxicity of titanium dioxide nanoparticles (TiO2 NPs), but there are very limited data on ecotoxicity to aquatic life. This paper is an observational study where we aim to describe the toxicity of TiO2 NPs to the main body systems of rainbow trout. Stock solutions of dispersed TiO2 NPs were prepared by sonication without using solvents. A semi-static test system was used to expose rainbow trout to either a freshwater control, 0.1, 0.5, or 1.0 mg l(-1) TiO2 NPs for up to 14 days. Exposure to TiO2 NPs caused some gill pathologies including oedema and thickening of the lamellae. No major haematological or blood disturbances were observed in terms of red and white blood cell counts, haematocrit values, whole blood haemoglobin, and plasma Na+ or K+ concentrations. Tissue metal levels (Na+, K+, Ca2+ and Mn) were generally unaffected. However, some exposure concentration dependent changes in tissue Cu and Zn levels were observed, especially in the brain. Exposure to TiO2 NPs caused statistically significant decreases in Na+K+ ATPase activity (ANOVA, P<0.05) in the gills and intestine, and a trend of decreasing enzyme activity in the brain (the latter was not statistically significant). Thiobarbituric acid reactive substances (TBARS) showed exposure concentration-dependent and statistically significant (ANOVA or Kruskal-Wallis test, P<0.05) increases (two-fold or more) in the gill, intestine and brain, but not the liver during exposure to TiO2 NPs compared to controls. TiO2 NP exposure caused statistically significant (ANOVA, P<0.05) increases in the total glutathione levels in the gills, but depletion of hepatic glutathione compared to controls. Total glutathione levels in the brain and intestine were unaffected. Liver cells exposed to TiO2 NPs showed minor fatty change and lipidosis, and some hepatocytes showed condensed nuclear bodies (apoptotic bodies). Fish probably ingested water containing TiO2 NPs during exposure (stress-induced drinking) which may have resulted in some areas of erosion on the intestinal epithelium. Overall we conclude that titanium dioxide nanoparticles are not a major ionoregulatory toxicant, or haemolytic, at the concentration and exposure times used. Respiratory distress is a concern and sub-lethal toxicity involves oxidative stress, organ pathologies, and the induction of anti-oxidant defences, such as glutathione. PMID- 17727976 TI - Sequences necessary for trans-splicing in transiently transfected Brugia malayi. AB - Many genes in parasitic nematodes are both cis- and trans-spliced. Previous studies have demonstrated that a 7nt element encoded in the first intron of the Brugia malayi 70kDa heat shock protein (BmHSP70) gene was necessary to permit trans-splicing of transgenic mRNAs in embryos transfected with constructs encoding portions of the BmHSP70 gene. Here we demonstrate that this element (the B. malayi HSP70 trans-splicing motif, or BmHSP70 TSM) is necessary and sufficient to direct trans-splicing of transgenic mRNAs derived from two genes naturally containing this motif. Mutations introduced into any position of the BmHSP70 TSM abrogated its ability to direct trans-splicing. Transgenic mRNAs derived from embryos transfected with constructs containing promoters and associated downstream domains from two normally trans-spliced genes that lack a BmHSP70 TSM homologue (the B. malayi 12kDa small subunit ribosomal protein (BmRPS12) gene and the B. malayi RNA-binding protein (BmRBP1) gene), were not trans-spliced. Transfer of the BmHSP70 TSM into the first intron of the BmRPS12 gene rendered it competent for trans-splicing. Insertion of the BmHSP70 TSM into the single intron of the BmRBP1 gene did not render it trans-splicing competent. However, tagged constructs of the full-length BmRBP1 gene were trans-splicing competent. An analysis of the first exons and introns of over 200 trans-spliced B. malayi genes found homologues for the BmHSP70 TSM in roughly 25%. Thus, while the BmHSP70 TSM is necessary and sufficient to direct trans-splicing in some genomic contexts, independent trans-splicing signals are employed by other genes. PMID- 17727977 TI - Biochemical properties of an intracellular serpin from Echinococcus multilocularis. AB - A serpin of the intracellular type from the tapeworm Echinococcus multilocularis was expressed in Escherichia coli, purified by ion exchange chromatography and tested for inhibitory activity against several proteinases. The recombinant protein, which after transcriptional induction, represents about 20 % of total cellular protein, is biochemically active and inhibits trypsin and the trypsin like plasmin as well as pig pancreatic and human neutrophil elastase. Implications regarding its biochemistry and biological function are discussed. PMID- 17727978 TI - Antifolate screening using yeast expressing Plasmodium vivax dihydrofolate reductase and in vitro drug susceptibility assay for Plasmodium falciparum. AB - The presence of homologous point mutations in the dhfr gene in Plasmodium vivax and Plasmodium falciparum is associated with resistance to antifolate drugs. The spread of antifolate resistance encouraged research for novel antifolate drugs active against both wild-type and dhfr-mutant strains of malaria parasites. Because P. vivax cannot be easily maintained in culture, we transformed a Saccharomyces cerevisiae DHFR-deleted mutant to express wild-type P. vivax dhfr gene and its mutant forms. Twenty-five dicyclic and tricyclic 2,4 diaminopyrimidine derivatives were screened. Six quinazoline compounds showed selective inhibition of yeast transformants expressing P. vivax dhfr genes. The 50% inhibitory concentration (IC(50)) of these six compounds was determined against field isolates of P. falciparum. Our results suggest that a close relationship between the yeast assay based on expression of P. vivax dhfr genes and the in vitro test using P. falciparum parasites in culture is a promising initial step for drug screening. PMID- 17727980 TI - Constrictive pericarditis as an emerging manifestation of hyper-IgG4 disease. AB - A 68-year-old Japanese man was admitted for evaluation of right pleural effusion and bilateral leg edema that had progressively worsened over 6 months. As chest computed tomography revealed marked pericardial thickening, we performed a pericardiectomy, resulting in the remarkable improvement of his clinical manifestations. However, pleural fibrosis associated with fever of unknown origin soon developed. An elevated serum level of serum IgG4 and infiltration of IgG4 positive plasma cell in the resected pericardium were identified; thus, our patient might have hyper-IgG4 disease. Our case is the first report describing constrictive pericarditis as an initial manifestation of hyper-IgG4 disease. PMID- 17727979 TI - Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) receptor specific peptide analogues for PET imaging of breast cancer: In vitro/in vivo evaluation. AB - Vasoactive intestinal peptide and pituitary adenylate cyclase activating peptide have high affinity for VPAC1, VPAC2 and PAC1 receptors overexpressed on human cancer cells. Four potent analogues of these peptides, TP3939, TP3982, TP4200 and TP3805 were labeled with (64)Cu and evaluated ex vivo and in vivo to asses their biological activity and receptor specificity. The ultimate goal is to utilize (64)Cu analogues for positron emission tomography (PET) imaging of breast cancers in humans. Radiochemical purity of each analogue was >92%. The muscle relaxivity assay revealed IC(50) to be 5.3x10(-8) M, 4.4x10(-8) M, 8.1x10(-8) M, 8.1x10(-9) M and Kd values determined by receptor specific cell binding assays were 3.3 nM, 0.33 nM, 0.2 nM and 0.72 nM for TP3805, TP3939, TP3982, and TP4200 respectively. The receptor affinity, using human breast cancer tissues, was 10.93 times greater than normal breast tissues. RT-PCR confirmed increased VPAC1 receptor expression on human breast tumor cells over normal cells and corroborated with autoradiography data. The blood clearance was rapid and in vivo translocation of (64)Cu to plasma protein was <15%. Data demonstrate that these analogues are potent, have uncompromised biological activity and are worthy of further evaluation for accurate PET imaging of human breast cancers and in determining malignant and benign lesions. PMID- 17727981 TI - Effects of oral appliances and CPAP on the left ventricle and natriuretic peptides. AB - BACKGROUND: In patients without cardiac disease, obstructive sleep apnea-hypopnea syndrome (OSAHS) is associated with systolic and diastolic dysfunction and left ventricular hypertrophy. Although continuous positive airway pressure (CPAP) therapy has been demonstrated to improve left ventricular structure and function in these patients, the effects of oral-appliance therapy on cardiac function are largely unknown. The aims of this study were to determine the left ventricular structure and function and natriuretic peptides in untreated OSAHS patients without cardiovascular disease, and to compare the effects of oral-appliance with CPAP therapy. METHODS: In 28 moderate to severe OSAHS patients echocardiography and measurements of concentrations of the amino-terminal fragment of pro-brain natriuretic peptide (NT-pro-BNP) were performed. Fifteen patients were randomized to oral-appliance and 13 to CPAP therapy. After 2 to 3 months of treatment echocardiography and NT-pro-BNP measurements were repeated. RESULTS: Of the 28 patients, 7 had left ventricular hypertrophy, 6 had left ventricular dilatation, and 3 had elevated NT-pro-BNP values. No significant improvements in echocardiographic outcomes were observed following treatment. The median NT-pro BNP values improved significantly following oral-appliance therapy (52 pg/ml to 22 pg/ml) whereas not following CPAP therapy (31 pg/ml to 37 pg/ml). CONCLUSIONS: This study demonstrates that 50% of patients with moderate to severe OSASH, without cardiovascular disease, have left ventricular hypertrophy, left ventricular dilatation or elevated natriuretic peptides. Significant changes in NT-pro-BNP values indicate an improvement of cardiac function following effective oral-appliance therapy. PMID- 17727982 TI - In-stent restenosis and thrombosis 41 months after drug-eluting stent implantation. AB - Evidence indicates that very late stent thrombosis (>1 year) occurs more frequently in drug-eluting stents than in bare metal stents after discontinuation of clopidogrel. We present a case of an 83 year old man with an LAD in-stent thrombosis 41 months after stenting with a sirolimus-eluting stent in whom clopidogrel was discontinued after 6 months based on these days' guidelines. In stent thrombus was aspirated and intracoronary ultrasound (ICUS) showed significant in-stent restenosis which had narrowed the minimal lumen diameter by 1 mm. The lesion was stented with a bare metal stent. The patient was discharged after recovery and had no recurrence of stent thrombosis in one month follow-up. We recommended indefinite dual antiplatelet therapy with aspirin and clopidogrel. PMID- 17727983 TI - Cardiac rhabdomyoma in an adult patient presenting with right ventricular outflow tract obstruction. AB - We present a 24 year old woman with cardiac rhabdomyoma. Cardiac rhabdomyoma is the most common benign cardiac tumor in infants, but in adults, cardiac rhabdomyoma is very rare. These tumors are often spontaneously reversible because they are associated to the right or left ventricular outflow tract obstruction, tachyarrhythmias and heart failure where surgery is necessary. PMID- 17727984 TI - A young man with intractable ascites and effort dyspnoea without echocardiographic signs of pericardial thickening: the importance of clinical investigation, CT scan and MRI in the diagnosis of constrictive pericarditis. AB - A 35-year-old male patient suffering from dyspnoea on effort for 8 months, with abdominal and jugular venous distension, was previously studied in another hospital and discharged with a diagnosis of restrictive cardiomyopathy. Physical examination revealed a blood pressure of 110/60 mm Hg and absence of pericardial knock and also of paradoxical pulse. Chest X-ray showed no cardio-pulmonary alterations. Transthoracic echocardiography showed mild LV dysfunction (LVEF 46%) and lack of pericardial effusion and thickening. Doppler interrogation of transmitral flow showed a restrictive pattern. Computed tomography showed diffusely thickened pericardium, with the absence of calcification and of pericardial effusion. Cardiac magnetic resonance confirmed pericardial thickening and showed lack of myocardial alterations. Mild LV dysfunction was noted with dyskinesia of interventricular septum. The patient underwent cardiac catheterization, demonstrating an equalisation of RV and LV diastolic pressures with "square root" sign. The patient underwent pericardiectomy with consequent resolution of his symptoms and improvement of LV function. PMID- 17727985 TI - AB0 system and D(Rh o) antigen frequencies in left ventricular hypertrabeculation/noncompaction in relation to cardiac and neuromuscular findings. AB - BACKGROUND: Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality with suspected genetic background, characterized by trabeculations and intertrabecular recesses. Aim of the study in LVHT patients was to assess the AB0 system and D(Rh(o)) antigen frequencies, to look for an association between the prevalence of cardiac and neuromuscular abnormalities and to compare distribution of the AB0 system and D(Rh(o)) antigen frequencies with the Austrian general population. METHODS AND RESULTS: In 77/102 LVHT patients (75%) information about blood group could be obtained. There were no differences in the prevalence of clinical, electrocardiographic and echocardiographic findings and neuromuscular disorders between the AB0 blood groups. When comparing 67 LVHT patients who were D(Rh(o)) antigen positive with 10 patients who were D(Rh(o)) antigen negative, no differences could be found. Among LVHT patients, 0 D(Rh(o)) antigen positive was the most frequent (39%) followed by A D(Rh(o)) antigen positive (34%). In the Austrian general population A D(Rh(o)) antigen positive was the most frequent (33%) followed by 0 D(Rh(o)) antigen positive (30%). CONCLUSION: This study shows that LVHT patients do not differ according the blood groups, and that the distribution of blood groups is only minimally different between LVHT patients and the general Austrian population. PMID- 17727987 TI - Quality assurance of dosimetry and the impact on sample size in randomized clinical trials. AB - BACKGROUND AND PURPOSE: The aim of this study was to investigate the impact of appropriate dosimetry quality assurance (QA) on patient number required in radiotherapy randomized control trials (RCT). MATERIALS AND METHODS: The steepness of clinical dose-response curves, gamma(clin.), was calculated by a convoluting a biological dose-response distribution and the distribution of technical and dosimetrical factors. Population size calculation was performed taking into account gamma(clin.) and expected difference in outcome between two arms of an RCT, for different levels of variation in dose to the patient population. RESULTS: Uncertainties in dose reduces gamma(clin.) to the largest extent when the initial gamma-value is high and less so for low gamma-value. Reduced uncertainty in dose led to a significant reduction in the number of patients required in an RCT if the expected difference between the experimental and conventional arm is small. The reduction in patient numbers is less when the differences between the conventional and experimental arm is larger. CONCLUSION: The number of patients required in an RCT may be reduced by introducing appropriate dosimetry QA as the risk of under-powering the study is minimized. Dosimetry QA in clinical studies is therefore cost-effective. PMID- 17727986 TI - Inflammation, endothelial dysfunction and angiogenesis markers in chronic heart failure patients. AB - This study was conducted to assess the relationship among circulating markers of inflammation, endothelial dysfunction and angiogenesis in 59 chronic heart failure (CHF) patients. Increased concentrations of C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-alpha), von Willebrand factor (VWF) and fibrinogen are strongly implicated in the development of CHF. Increased vascular endothelium grow factor (VEGF) and decreased thrombospondin-1 (TSP-1) concentrations suggest a role of angiogenesis in the maintenance and repair of luminal endothelium in CHF. A relationship among markers of endothelial dysfunction (VWF) and inflammation (fibrinogen, CRP) and angiogenesis (VEGF, TSP 1) was found in CHF patients. PMID- 17727988 TI - Defining internal target volume (ITV) for hepatocellular carcinoma using four dimensional CT. AB - BACKGROUND AND PURPOSE: To define individualized internal target volume (ITV) for hepatocellular carcinoma using four-dimensional computed tomography (4DCT). MATERIALS AND METHODS: Gross tumor volumes (GTVs) and clinical target volumes (CTVs) were contoured on all 10 respiratory phases of 4DCT scans in 10 patients with hepatocellular carcinoma. The 3D and 4D treatment plans were performed for each patient using two different planning target volumes (PTVs): (1) PTV(3D) was derived from a single CTV plus conventional margins; (2) PTV(4D) was derived from ITV(4D), which encompassed all 10 CTVs plus setup margins (SMs). The volumes of PTVs and dose distribution were compared between the two plans. RESULTS: The average PTV volume of the 4D plans (328.4+/-152.2cm(3)) was less than 3D plans (407.0+/-165.6cm(3)). The 4D plans spared more surrounding normal tissues than 3D plans, especially normal liver. Compared with 3D plans, the mean dose to normal liver (MDTNL) decreased from 22.7 to 20.3Gy. Without increasing the normal tissue complication probability (NTCP), the 4D plans allowed for increasing the calculated dose from 50.4+/-1.3 to 54.2+/-2.6Gy, an average increase of 7.5% (range 4.0-16.0%). CONCLUSIONS: The conventional 3D plans can result in geometric miss and include excess normal tissues. The 4DCT-based plans can reduce the target volumes to spare more normal tissues and allow dose escalation compared with 3D plans. PMID- 17727989 TI - Facilitated activation of metabotropic glutamate receptors in cerebellar Purkinje cells in glutamate transporter EAAT4-deficient mice. AB - Around excitatory synapses in cerebellar Purkinje cells (PCs), GLAST and EAAT4 are expressed as predominant glial and neuronal glutamate transporters, respectively. EAAC1, another subtype of neuronal glutamate transporter, is also expressed in PCs. EAAT4 is co-localized with metabotropic glutamate receptors (mGluRs) at perisynaptic sites in excitatory synapses in PCs, and this neuronal transporter was reported to be involved in the regulation of mGluR activation induced by the stimulation of parallel fibers (PFs). However, it remains to be elucidated whether only EAAT4 is specifically involved in mGluR activation among the glutamate transporters expressed near excitatory synapses in PCs. Here we examined mGluR-mediated excitatory postsynaptic currents (mGluR-EPSCs) evoked by PF stimulation in cerebellar slices of mice deficient in EAAT4, EAAC1, or GLAST. PF-evoked mGluR-EPSCs showed larger amplitude and faster rising kinetics in EAAT4 deficient mice than in the wild-type mice. In contrast, there was no significant difference in either the amplitude or the rising kinetics of mGluR-EPSCs in GLAST or EAAC1-deficient mice compared to wild-type mice. We conclude that EAAT4 is most closely involved in mGluR activation in PCs among the glutamate transporters. PMID- 17727990 TI - Enumeration and identification of Campylobacter species in the liver and bile of slaughtered cattle. AB - Healthy cattle are considered as reservoirs for a variety of Campylobacter species. To control the bacterial contamination in meat products, quantitative assessment of campylobacters in liver and gallbladder was carried out at an abattoir. Liver and bile samples were collected from 108 healthy beef cattle after evisceration and viable counts of campylobacters were determined by a direct-plating technique using modified Cefoperazone Charcoal Deoxycholate agar (mCCDA). The suspected colonies on the highest dilution plates were subjected to biochemical tests and PCR for identification. Campylobacter species were isolated from 49 (45%) bile and 6 (5%) liver specimens examined. Numbers of campylobacters in bile and liver ranged from log(10)3 to 7 (median 5) and log(10) 1 to 2 (median 1) cfu per ml and per g, respectively. These Campylobacter species were identified as C. fetus, C. jejuni, and C. coli. Multiple infections involving two species were observed in 16 cattle. C. fetus and C. jejuni were the predominant species in bile. Growth of C. fetus, C. jejuni, and C. coli in spiked bile samples revealed an initial exponential growth phase followed by a period with no apparent increase in colony count for 28 days. It appeared that these campylobacters can survive in bile for a long period. To determine transfer route of bacterial cells to the gallbladder, C. jejuni, C. fetus, or C. coli was inoculated intravenously in mice. The inoculated cells were recovered from bile, suggesting that the organism was transferred from the blood stream to bile duct in the liver. From these results, bile in cattle is considered to be an important contamination source of Campylobacter species in processing plants. PMID- 17727991 TI - Quantification of total viable bacteria on fish fillets by using ethidium bromide monoazide real-time polymerase chain reaction. AB - Real-time PCR based on universal primers for amplification of a highly conserved bacterial 16S rDNA sequence was utilized in conjunction with the treatment of extracted bacterial cells with ethidium bromide monoazide (EMA) for the differential enumeration of viable and dead cells on cod fillets. Amplification of DNA from dead bacterial cells was successfully inhibited by EMA, whereas the DNA from viable cells was readily amplified. The detection range of the EMA real time PCR assay was linear from 1 x 10(1) to 1 x 10(5) mixed bacterial genomic targets per PCR derived from broth cultures of fish tissue. The minimum detection limit of bacteria was found to be 1 x 10(1) genomic units/real-time PCR, equivalent to 1 x 10(5) CFU per gram of tissue. The EMA real-time PCR allowed construction of a standard curve obtained by plotting the log of genomic targets from strictly viable cells against resulting PCR cycles (Ct values) that facilitated quantification of total viable bacteria from fish fillets. The log of the total number of genomic DNA targets from EMA treated cells and plate counts from six randomly procured cod fillets were found not to be statistically different with the exception of one fillet. The process of freezing and thawing fillet tissue resulted in a drop in mean colony forming units (CFU) detected by plate counts from log 8.5+/-0.2 to log 8.1+/-0.1. A similar reduction in genomic targets from 8.5+/-0.1 to 8.0+/-0.16 was detected by EMA real-time PCR. PMID- 17727992 TI - Toward an improved laboratory definition of Listeria monocytogenes virulence. AB - Listeria monocytogenes is an opportunistic foodborne pathogen that encompasses a diversity of strains with varied virulence. The ability to rapidly determine the pathogenic potential of L. monocytogenes strains is integral to the control and prevention campaign against listeriosis. Early methods for assessing L. monocytogenes virulence include in vivo bioassays and in vitro cell assays. While in vivo bioassays provide a measurement of all virulence determinants of L. monocytogenes, they are not applied routinely due to their reliance on experimental animals whose costs have become increasingly prohibitive. As a low cost alternative, in vitro cell assays are useful for estimating the virulence of L. monocytogenes strains. However, these assays are often slow, and at times variable. Prior attempts to ascertain L. monocytogenes virulence by targeting virulence-associated proteins and genes have been largely unsuccessful, since many of the assay targets are present in both virulent and avirulent strains. Recent identification of novel virulence-specific genes (particularly internalin gene inlJ) has opened a new avenue for rapid, sensitive, and precise differentiation of virulent L. monocytogenes strains from avirulent strains. The application of DNA sequencing technique also offers an additional tool for assessing L. monocytogenes virulence potential. By providing an update on the laboratory methods that have been reported for the determination of L. monocytogenes pathogenicity, this review discusses future research needs that may help achieve an improved laboratory definition of L. monocytogenes virulence. PMID- 17727993 TI - The mycotoxin threat to food safety. PMID- 17727994 TI - Escherichia coli O26 in minced beef: prevalence, characterization and antimicrobial resistance pattern. AB - Verocytotoxin-producing Escherichia coli (VTEC) non-O157 serogroups are among the most important emerging food-borne pathogen groups. In particular, the O26 serogroup is able to cause a large spectrum of illnesses in humans which have a significant public health impact as they may range from haemorrhagic colitis (HC) to haemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). It is known that VTEC organisms are associated with animal reservoirs, i.e. ruminants, and foods of animal origin, especially undercooked meat and raw milk, are often involved in outbreaks. In this study, 250 minced beef samples collected at retail outlets in southern Italy were tested for the presence of E. coli O26 and the isolates were characterized and studied for their antimicrobial resistance properties. Three minced beef samples (1.2%) tested positive for E. coli O26; one isolate per positive sample was characterized. One isolate harboured the genes encoding for virulence factors intimin (eaeA) and enterohaemolysin (hlyA), while none presented verocytotoxin-encoding genes (stx1 and stx2) and all were negative at the verotoxicity assay. All the isolates showed resistance properties to at least four antimicrobial agents tested and two were multi-drug resistant (MDR). Although no verocytotoxin-encoding genes were found in the isolates, the presence of potentially pathogenic E. coli O26 strains in minced beef points to the need for proper hygiene during meat production to reduce the risk of food-borne illnesses and transmission of MDR organisms via foods to humans. This paper is the first report on the presence and characterization of E. coli O26 in minced beef marketed in Italy. PMID- 17727995 TI - Characterization of Staphylococcus aureus strains isolated from bovine milk in Hungary. AB - Staphylococcus aureus is a major foodborne pathogen due to its capability to produce a wide range of heat-stable enterotoxins. The primary purpose of this research was to characterize S. aureus isolates recovered from mammary quarter milk of mastitic cows and from bulk tank milk produced on Hungarian dairy farms of different sizes. Macrorestriction analysis of chromosomal DNA from S. aureus isolates was performed using the restriction enzyme SmaI followed by pulsed-field gel electrophoresis (PFGE). The prevalence rates of nine S. aureus enterotoxin genes (sea, seb, sec, sed, see, seg, seh, sei, and sej) and of the toxic shock syndrome toxin 1 gene (tst) were determined by multiplex polymerase chain reaction (PCR). The bulk tank milks of 14 out of 20 farms were contaminated with S. aureus at levels of up to 6.0x10(3 )CFU/ml. Farm size had no significant effect (P>0.05) on the S. aureus counts in bulk milk. The prevalence rates of penicillin resistance were 88.9% and 20.0% among the S. aureus recovered from mastitic quarter milk and bulk tank milk, respectively. After phenotypic characterization, a total of 59 S. aureus isolates were selected for genotyping. PFGE analysis revealed 22 distinct pulsotypes, including 14 main types and 8 subtypes, at a similarity level of 86%. Only one or two main types were observed on each of the farms tested, indicating a lack of genetic diversity among S. aureus isolates within farms, and there were only two pulsotypes which occurred on more than one farm. The PFGE patterns showed genetic relatedness between the S. aureus strains recovered from quarter milk and bulk milk on two large farms, implying that on farms having a high number of mastitic cows, S. aureus from infected udders may contaminate bulk milk and, subsequently, raw milk products. Sixteen (27.1%) of the S. aureus isolates tested by multiplex PCR were found to be positive for enterotoxin genes, with 15 of them carrying just one gene and one strain carrying two genes (seg and sei). The most commonly detected toxin genes were seb, sea, and sec, whereas none of our isolates possessed the see, seh, sej, or tst genes. On 75% of the dairy farms surveyed, no enterotoxigenic staphylococci were recovered from either mastitic quarter milk or bulk tank milk. PMID- 17727996 TI - Opportunities for biotechnology and policy regarding mycotoxin issues in international trade. AB - Despite being introduced more than a decade ago, agricultural biotechnology still remains framed in controversy impacting both the global economy and international regulations. Controversies surrounding agricultural biotechnology produced crops and foods commonly focus on human and environmental safety, intellectual property rights, consumer choice, ethics, food security, poverty reduction and environmental conservation. Originally, some consumers were reluctant to accept the first generation agricultural biotechnology products because they appeared to primarily benefit agricultural producers; however, it is clear from continued evaluations that these technologies also improved both the safety and wholesomeness of food and helped improve the environment. Plants engineered to resist insect pests and tolerate less toxic pesticides resulted in improved yields thereby enabling farmers to produce more food per acre while reducing the need for herbicides, pesticides, and water and tilling. An indirect benefit of reduced pest damage in transgenic corn expressing genes to control insect pests is lower levels of mycotoxins, most notably those caused by the genus Fusarium. Mycotoxins are an important regulatory issue globally because of their toxic and carcinogenic potential to humans and animals. Complicating this issue is the fact that toxicological databases for mycotoxins are relatively incomplete compared to other food contaminants. Current debates about agricultural biotechnology and mycotoxins reveal significant differences in perception of associated risks and benefits. When faced with uncertainty, regulators tend to set limits as low as possible. Additionally, some regulators invoke the "Precautionary Principle" when limited information is available or disputes over interpretation exist for possible contaminants, including mycotoxins. A major concern regarding use of the "Precautionary Principle" is the appearance that regulators can justify setting any limit on the basis of inconclusive or unknown potential hazards of a contaminant which may significantly impact global trade because mycotoxin residues vary widely between countries. This paper describes the current economic and heath impact of these regulations and their impact on international trade. PMID- 17727997 TI - Prevalence of pathogenic Yersinia enterocolitica in pigs slaughtered at a Swiss abattoir. AB - Human yersiniosis is the third most common enteric disease after campylobacteriosis and salmonellosis in many European countries. However, epidemiological data on the prevalence of pathogenic Yersinia enterocolitica in animals and humans is insufficient. Pigs are assumed to be the main reservoir of pathogenic Y. enterocolitica because pig is so far the only animal species from which pathogenic strains have frequently been isolated. This work was conducted to study the frequency of ail-positive Y. enterocolitica in pigs slaughtered at a Swiss abattoir. In total, 212 pig tonsils were screened by real-time PCR and culture methods. The prevalence rate of ail-positive Y. enterocolitica in pigs at slaughter was 88% and 34% with PCR and culture methods, respectively. The 148 ail positive isolates from the 72 culture-positive tonsils were bio-and serotyped. The most common bioserotype was 4/O:3 found in 96% (69/72) of the culture positive samples. However, pig was also shown to be a reservoir for ail-positive Y. enterocolitica belonging to bioserotypes 2/O:5,27 and 2/O:9, which were detected in 8% (6/72) and 1% (1/72) of the culture-positive samples, respectively. Using PFGE with NotI, only a limited number of different patterns was found. In all, 6 genotypes were obtained when 86 isolates of bioserotype 4/O:3 from 69 samples were characterised and two genotypes (N1 and N4) dominated. The biotype 4 differs clearly from biotype 2 with PFGE. Antimicrobial resistance testing of 77 ail-positive Y. enterocolitica isolates from 72 samples studied with disc-diffusion revealed that all strains were sensitive to cefotaxime, chloramphenicol, ciprofloxacin and tetracycline, which are antimicrobial agents used for treatment of human disease. The isolates of bioserotype 2/O:5,27 differed from the isolates of bioserotypes 2/O:9 and 4/O:3 in resistance to ampicillin and amoxicillin/clavulanic acid. PMID- 17727998 TI - Mold and mycotoxin problems encountered during malting and brewing. AB - Fusarium infections in grains can have severe effects on malt and beer. While some degree of Fusarium mycotoxins, such as deoxynivalenol, present in infected barley may be lost during steeping, the Fusarium mold is still capable of growth and mycotoxin production during steeping, germination and kilning. Therefore, detoxification of grain before malting may not be practical unless further growth of the mold is also prevented. Methods to reduce the amount of mold growth during malting are needed. Physical, chemical and biological methods are reviewed. Irradiation looks very promising as a means to prevent Fusarium growth during malting, but the effect on the surviving mold to produce mycotoxins and the effect on malt quality needs further study. Chemical treatments such as ozonation, which would not leave residual chemical in the beer also appear to be promising. Although biological control methods may be desirable, due to the use of "natural" inhibition, the effects of these inhibitors on malt and beer quality requires further investigation. It may also be possible to incorporate detoxifying genes into fermentation yeasts, which would result in detoxification of the wort when mold growth is no longer a problem. Development of these types of technological interventions should help improve the safety of products, such as beer, made from Fusarium infected grain. PMID- 17727999 TI - Receptor-mediated gene delivery by folate-PEG-baculovirus in vitro. AB - Gene delivery using baculovirus is a promising approach for efficient and safe gene therapy compared with animal viruses. However, obstacles of baculovirus mediated gene delivery include inactivation of baculovirus in human serum and whole blood and the lack of specificity in targeted delivery. Therefore, chemical modification of the viral surface with poly(ethylene glycol) (PEG) and a targeting ligand, such as folate, is necessary for stable and targeted gene delivery via receptor-mediated endocytosis. In this study, folate-PEG (F-PEG) was attached on the baculovirus surface to obtain efficiency and specificity of gene delivery. Composition of F-PEG and degree of capsid modification with F-PEG was determined using (1)H nuclear magnetic resonance ((1)H NMR) and fluorescamine assay, respectively. Folate-PEG-Baculovirus (F-P-Bac) showed enhanced transduction efficiency compared to PEG-Baculovirus (P-Bac) in folate receptor (FR)-positive KB cells. Moreover, this enhanced transduction was not observed in FR-negative HepG2 cells. Presence of free folate in the medium blocked the transduction of F-P-Bac, whereas transduction efficiency of P-Bac in the presence or absence of free folate was not changed significantly. This study thus suggests that F-P-Bac can be used as a receptor-mediated gene delivery system. PMID- 17728000 TI - Lectin-conjugated PLGA nanoparticles loaded with thymopentin: ex vivo bioadhesion and in vivo biodistribution. AB - The conjugation of lectins onto PLGA nanoparticles has been demonstrated to effectively improve the intestinal absorption of thymopentin. In this study, thymopentin-loaded nanoparticles made from fluorescein isothiocyanate labeled PLGA were modified with wheat germ agglutinin (WGA). The specific bioadhesion of nanoparticles on rat intestinal mucosa was studied ex vivo. An important increase of interaction between WGA-conjugated nanoparticles and the intestinal segments was observed compared with that of the unconjugated one (p<0.05). Fluorescence photomicrographs confirmed the bioadhesion of WGA-conjugated nanoparticles on intestinal villous epithelium as well as Peyer's patches. Biodistribution of nanoparticles was evaluated using tissues obtained from rats, to which nanoparticles were orally administered. The highest amount of WGA-conjugated nanoparticles was detected in small intestine, suggesting an increase of intestinal bioadhesion and endocytosis. The systemic uptake was as high as 6.48 13.4% of dose at 1 day and 7.32-15.26% at 7 days, which representing an increase of almost 1.4-3.1 fold across the intestine compared to <4.9% of the unconjugated one. The enhanced uptake was related to the increasing of WGA density on nanoparticles. These results further revealed the promising potential of lectin conjugated nanoparticles on the improvement of intestinal bioadhesion and absorption for oral drug delivery. PMID- 17728001 TI - Random and block copolymers of bioreducible poly(amido amine)s with high- and low basicity amino groups: study of DNA condensation and buffer capacity on gene transfection. AB - Poly(amido amine) (SS-PAA) random and block copolymers having bioreducible disulfide bonds in the main chain and amino groups with distinctly different basicity in the side chain were designed and synthesized by Michael addition polymerization between N, N'-cystaminebisacrylamide (CBA) and two amine monomers, i.e., histamine (HIS) and 3-(dimethylamino)-1-propylamine (DMPA). Copolymers containing variable HIS/DMPA ratios show higher ability to bind DNA than p(CBA HIS) homopolymer and condense DNA into the polyplexes with particle sizes (<150 nm) that are smaller than polyplexes of p(CBA-HIS) ( approximately 220 nm). The buffer capacities of the copolymers increase with increasing HIS/DMPA ratio. These copolymers are able to transfect COS-7 cells in vitro with efficiencies that increase with increasing HIS/DMPA ratio. The random and block copolymers at a HIS/DMPA ratio of 70/30 combines optimal DNA condensation capability and buffer capacity, thereby inducing higher transfection efficiency in the absence and presence of serum as compared to p(CBA-HIS) homopolymer. Moreover, random and block copolymers show a similar transfection capacity, but both have higher capacity than the physical mixtures of p(CBA-HIS) and p(CBA-DMPA) homopolymers. XTT assay reveals that the polyplexes of the SS-PAA copolymers have essentially low cytotoxicity when the highest transfection activity is observed. PMID- 17728002 TI - Duplicative medications in patients who visit multiple medical institutions among the insured of a corporate health insurance society in Japan. AB - OBJECTIVE: The objective of this paper is to describe the frequency of duplicative medication use and to estimate the drug cost associated with duplicative medications in patients who visit multiple medical institutions in Japan. METHODS: The subjects of this study were insurants of a corporate health insurance society. We examined claims of insurants who received prescriptions from multiple medical institutions in April 2002. We examined characteristics of insurants who received duplicative medications and calculated the cost of duplicated drugs. RESULTS: 8.8% received drugs with the same mechanism of action for overlapping administration periods. In terms of comparison among three age groups, 0-19 years old, 20-69 years old, and 70 years old or older, the percentage was higher in 0-19-year-old patients than in the other age groups. The cost of duplicated drugs was found to be 0.7% or 0.5% of the total drug cost, when calculated with higher-priced drugs and lower-priced drugs, respectively. CONCLUSIONS: This study suggests that pediatric and teenage patients as well as elderly patients require prudent management of medication to avoid duplicative medications and that at least an estimated 5.2-7.2 billion yen may be saved if duplicative medications can be completely eliminated nationwide. PMID- 17728003 TI - Economic evaluation of cystic fibrosis screening: a review of the literature. AB - OBJECTIVES: To critically examine the economic evidence regarding cystic fibrosis (CF) carrier screening and to understand issues relating to the transferability of international findings to any national context for policy decisions. METHODS: A systematic literature search identified 14 studies (out of 29 economic studies on CF) focusing on preconception or prenatal screening between 1990 and 2006. These studies were then assessed against international benchmarks on conducting and reporting of economic evaluations, costing methodology used and focusing on the transferability of the evidence to national contexts. RESULTS: The primary outcome measures varied considerably between studies and there was considerable ambiguity and variation on how costs were estimated. The Incremental Cost Effectiveness Ratio (ICER) and net savings, for preconception and prenatal screening were inconsistent and varied significantly, even after adjusting for timing and exchange rates. Differences in screening participation rates, reproductive choices, test sensitivity, cost of test and lifetime cost of care make up a large part of the ICER variations. CONCLUSION: The heterogeneity in study design, model inputs and reporting of economic evaluations of CF carrier screening makes comparability and transferability across countries and even within countries difficult. This reinforces the need to assess any technology within the relevant context, and to not simply generalize from reported studies. In turn, this adds to the complex task of making efficient resource allocation decisions in the area of CF carrier screening. Our evaluation adds weight to the calls for revisiting the way economic studies are conducted and reported. PMID- 17728004 TI - Preference heterogeneity and choice of cardiac rehabilitation program: results from a discrete choice experiment. AB - This paper focuses on the elicitation of patients' preferences for cardiac rehabilitation activities from a discrete choice experiment using a mixed model. We observed a high level of preference heterogeneity among patients for all the five cardiac rehabilitation activities--even when age and smoking status were taken into account. The random parameter model provided additional policy relevant information as well as a better fit to the data than did the standard logit model. The paper focuses on one of the potential problems with the standard logit specification which in the worst case can lead to wrong policy conclusions by assuming homogeneity in preferences across individuals. The generalised RPL specification may be a more appropriate specification that can provide additional information on the heterogeneity preferences. PMID- 17728005 TI - Overexpression of matrix metalloproteinase-7 (MMP-7) correlates with tumor proliferation, and a poor prognosis in non-small cell lung cancer. AB - BACKGROUND: Matrix metalloporteinase-7 (MMP-7) is a member of the MMP family, and it has been reported to play an important role in tumorigenesis, invasion and metastasis. We performed a retrospective study on the MMP-7 expression in non small cell lung cancer (NSCLC) according to the clinical characteristics, biological markers and the Wnt1 expression. PATIENTS AND METHODS: One hundred forty-seven postsurgical NSCLC patients were investigated. Immunohistochemistry was performed to evaluate the MMP-7 expression, the Ki-67 proliferation index, tumor angiogenesis and the Wnt1 expression. The TUNEL method was performed to investigate tumor apoptosis. RESULTS: Seventy-six carcinomas (51.7%) were MMP-7 positive. The MMP-7 expression was significantly higher in squamous cell carcinomas than in adenocarcinomas (P<0.0001). The Ki-67 proliferation index was significantly higher in MMP-7-positvie tumors than in MMP-7-negative tumors (P=0.0003). However, there was no difference in the MMP-7 expression in relation to apoptosis or angiogenesis. Regarding its regulation, the MMP-7 expression significantly correlated with the Wnt1 expression (r=0.426, P<0.0001). The overall survival was significantly lower in patients with MMP-7-positive NSCLCs than in those with MMP-7-negative NSCLCs (P=0.0018). A Cox regression analyses also demonstrated MMP-7 status to be a significant prognostic factor (hazard ratio, 2.187; P=0.0023). CONCLUSIONS: The overexpression of MMP-7 was associated with tumor proliferation, and a poor prognosis in NSCLCs. In addition, Wnt1 may play a critical role in regulating the intratumoral MMP-7 expression. PMID- 17728006 TI - let-7 microRNA expression is reduced in bronchioloalveolar carcinoma, a non invasive carcinoma, and is not correlated with prognosis. AB - It has been proposed that reduced let-7 expression causes RAS expression and correlates with poor survival of lung cancer cases, but little is known about correlations with clinicopathologic features. In this study, we examined 15 early bronchioloalveolar carcinomas (BACs), usually considered as adenocarcinomas in situ, as well as 26 well-differentiated and 25 less-differentiated invasive adenocarcinomas, to assess the association between tumor progression and let-7 expression levels. Additionally, we investigated 47 invasive lung adenocarcinomas for EGFR and KRAS mutations and correlations with let-7 levels. Relative to the corresponding normal lung tissue, reduced let-7 expression was observed in 13 of 15 BACs (87%) and totally in 52 of the 66 adenocarcinomas (79%), suggesting a link with early occurrence in carcinogenesis. On classification of adenocarcinomas into two groups according to let-7 expression, no prognostic or genetic differences were observed. Interestingly, some differences between histological subtypes were observed, such as lower let-7 expression levels in acinar adenocarcinomas and mucinous BACs. PMID- 17728007 TI - Groundwater vulnerability and risk mapping using GIS, modeling and a fuzzy logic tool. AB - A groundwater vulnerability and risk mapping assessment, based on a source pathway-receptor approach, is presented for an urban coastal aquifer in northeastern Brazil. A modified version of the DRASTIC methodology was used to map the intrinsic and specific groundwater vulnerability of a 292 km(2) study area. A fuzzy hierarchy methodology was adopted to evaluate the potential contaminant source index, including diffuse and point sources. Numerical modeling was performed for delineation of well capture zones, using MODFLOW and MODPATH. The integration of these elements provided the mechanism to assess groundwater pollution risks and identify areas that must be prioritized in terms of groundwater monitoring and restriction on use. A groundwater quality index based on nitrate and chloride concentrations was calculated, which had a positive correlation with the specific vulnerability index. PMID- 17728008 TI - Characterization of connexin30.3-deficient mice suggests a possible role of connexin30.3 in olfaction. AB - We have generated connexin30.3-deficient mice in which the coding region of the connexin30.3 gene was replaced by the lacZ reporter gene. The expression pattern of this connexin was characterized using beta-galactosidase staining and immunoblot analyses. In skin, beta-galactosidase/connexin30.3 protein was expressed in the spinous and granulous layers of the epidermis. Specific beta galactosidase/connexin30.3 expression was also detected in the thin ascending limb of Henle's loop in the kidney. In addition, we found beta galactosidase/connexin30.3 in progenitor cells of the olfactory epithelium and in a subpopulation of cells in the apical layer of the vomeronasal organ. Connexin30.3-deficient mice were fertile and displayed no abnormalities in the skin or in the chemosensory systems. Furthermore, they showed normal auditory thresholds as measured by brain stem evoked potentials. These mice did, however, exhibit reduced behavioural responses to a vanilla scent. PMID- 17728009 TI - Effects of cadmium on antioxidant enzyme and photosynthetic activities in leaves of two maize cultivars. AB - Effects of cadmium (Cd(2+)) on photosynthetic and antioxidant activities of maize (Zea mays L.) cultivars (3223 and 32D99) were investigated. Fourteen-day-old cultivar seedlings were exposed to different Cd concentrations [0, 0.3, 0.6 and 0.9mM Cd(NO(3))(2) x 4H(2)O] for 8 days. The results of chlorophyll fluorescence indicated that different levels of Cd affected photochemical efficiency in 3223 much more than that in 32D99. In parallel, the level of Cd at 0.9mM caused oxidative damage but did not indicate cessation of PSII activity of the cultivars; plant death was not observed at highly toxic Cd levels. Additionally, the increase in Cd concentration caused loss of chlorophylls and carotenoid and membrane damage in both cultivars, but greater membrane damage was observed in 3223 than in 32D99. Depending on Cd accumulation, a significant reduction in dry biomass was observed in both cultivars at all Cd concentrations. The accumulation of Cd was higher in roots than in leaves for both cultivars. Nevertheless, cultivar 3223 transferred more Cd from roots to leaves than did 32D99. On the other hand, our results suggest that there were similar responses in SOD, APX and GR activities with increasing Cd concentrations for both cultivars. However, POD activity significantly increased at highly toxic Cd levels in 32D99. This result may be regarded as an indication of better tolerance of the Z. mays L. cultivar 32D99 to Cd contamination. PMID- 17728010 TI - Suppression and promotion of growth by ethylene in rice seedlings depends on ambient humidity. AB - We examined the effect of ethylene on the growth of rice seedlings (Oryza sativa L.) at various degrees of humidity. Ethylene significantly suppressed the growth of shoots when applied to seedlings grown under 30% relative humidity (RH), but promoted the growth of shoots when applied to seedlings grown under 100% RH. The application of gibberellic acid (GA(3)) promoted the elongation of shoots in seedlings grown under 30% and 100% RH. Ethylene inhibited the shoot elongation induced by GA(3) at 30% RH, but enhanced the elongation induced by GA(3) at 100% RH. These results indicate that ethylene can either promote or suppress the growth of rice shoots depending on ambient humidity, and that these actions of ethylene may be mediated through modulating the responsiveness of shoots to gibberellin. PMID- 17728011 TI - Growth and nitrogen fixation in Lotus japonicus and Medicago truncatula under NaCl stress: nodule carbon metabolism. AB - Lotus japonicus and Medicago truncatula model legumes, which form determined and indeterminate nodules, respectively, provide a convenient system to study plant Rhizobium interaction and to establish differences between the two types of nodules under salt stress conditions. We examined the effects of 25 and 50mM NaCl doses on growth and nitrogen fixation parameters, as well as carbohydrate content and carbon metabolism of M. truncatula and L. japonicus nodules. The leghemoglobin (Lb) content and nitrogen fixation rate (NFR) were approximately 10.0 and 2.0 times higher, respectively, in nodules of L. japonicus when compared with M. truncatula. Plant growth parameters and nitrogenase activity decreased with NaCl treatments in both legumes. Sucrose was the predominant sugar quantified in nodules of both legumes, showing a decrease in concentration in response to salt stress. The content of trehalose was low (less than 2.5% of total soluble sugars (TSS)) to act as an osmolyte in nodules, despite its concentration being increased under saline conditions. Nodule enzyme activities of trehalose-6-phosphate synthase (TPS) and trehalase (TRE) decreased with salinity. L. japonicus nodule carbon metabolism proved to be less sensitive to salinity than in M. truncatula, as enzymatic activities responsible for the carbon supply to the bacteroids to fuel nitrogen fixation, such as sucrose synthase (SS), alkaline invertase (AI), malate dehydrogenase (MDH) and phosphoenolpyruvate carboxylase (PEPC), were less affected by salt than the corresponding activities in barrel medics. However, nitrogenase activity was only inhibited by salinity in L. japonicus nodules. PMID- 17728012 TI - Identification of a multigene family encoding putative beta-glucan-binding proteins in Medicago truncatula. AB - Branched 1,6-1,3-beta-glucans from Phytophthora sojae cell walls represent pathogen-associated molecular patterns (PAMPs) that have been shown to mediate the activation of plant defence reactions in many legumes. In soybean, a receptor protein complex containing a high affinity beta-glucan-binding protein (GBP) was identified and investigated in detail. In the model legume Medicago truncatula, used for functional genomic studies of various plant-microbe interactions, a high affinity beta-glucan-binding site was characterized biochemically. However, to date, none of the genes encoding GBPs from M. truncatula have been described. Here, we report the identification of four full-length clones encoding putative beta-glucan-binding proteins from M. truncatula, MtGBP1, 2, 3, and 4, composing a multigene family encoding GBP-related proteins in this plant. Differences in expression patterns as well as in regulation on treatment with two different biotic elicitors are demonstrated for the members of the GBP family and for a selection of defence-related genes. PMID- 17728013 TI - Aminoaldehyde dehydrogenase activity during wound healing of mechanically injured pea seedlings. AB - Aminoaldehyde dehydrogenase (AMADH, EC 1.2.1.19) is an enzyme that, in association with amine oxidase, participates in polyamine catabolism. In plants, the enzyme is well characterized in pea seedlings. In this study, we used etiolated and light-grown pea seedlings as model plants to evaluate the possible AMADH role in response to stress caused by mechanical damage. In the beginning, the activity distribution of AMADH, amine oxidase and peroxidase in organs of 7 day-old intact pea seedlings was analyzed. To perform mechanical damage, stems of 10-day-old seedlings were each divided into four segments of equal length. The top (=fourth) segments were then longitudinally cut with a lancet. During healing, the injured segments and their control counterparts were harvested in 1 day intervals and analyzed for activity of the above enzymes, polyamine and 4 aminobutyrate (GABA) concentrations. The injury elicited increases in AMADH, amine oxidase and peroxidase activities in both etiolated and green seedlings, accompanied by parallel increases in putrescine, cadaverine, spermidine and GABA content. Histochemical experiments allowed visualization of increased AMADH activity in cross sections obtained from the injured stem segments. The activity was localized in cortical parenchyma and epidermal cells adjacent to the wound site in spatial correlation with an intensive lignification. In the control seedlings, AMADH activity or lignification in these tissues could not be visualized. Thus, we conclude that, in plants, AMADH may participate in processes of adaptation to stress events caused by mechanical injury, which involve polyamine catabolism, GABA production and lignification. PMID- 17728014 TI - Can elevated CO(2) improve salt tolerance in olive trees? AB - We compared growth, leaf gas exchange characteristics, water relations, chlorophyll fluorescence, and Na(+) and Cl(-) concentration of two cultivars ('Koroneiki' and 'Picual') of olive (Olea europaea L.) trees in response to high salinity (NaCl 100mM) and elevated CO(2) (eCO(2)) concentration (700microLL(-1)). The cultivar 'Koroneiki' is considered to be more salt sensitive than the relatively salt-tolerant 'Picual'. After 3 months of treatment, the 9-month-old cuttings of 'Koroneiki' had significantly greater shoot growth, and net CO(2) assimilation (A(CO(2))) at eCO(2) than at ambient CO(2), but this difference disappeared under salt stress. Growth and A(CO(2)) of 'Picual' did not respond to eCO(2) regardless of salinity treatment. Stomatal conductance (g(s)) and leaf transpiration were decreased at eCO(2) such that leaf water use efficiency (WUE) increased in both cultivars regardless of saline treatment. Salt stress increased leaf Na(+) and Cl(-) concentration, reduced growth and leaf osmotic potential, but increased leaf turgor compared with non-salinized control plants of both cultivars. Salinity decreased A(CO(2)), g(s), and WUE, but internal CO(2) concentrations in the mesophyll were not affected. eCO(2) increased the sensitivity of PSII and chlorophyll concentration to salinity. eCO(2) did not affect leaf or root Na(+) or Cl(-) concentrations in salt-tolerant 'Picual', but eCO(2) decreased leaf and root Na(+) concentration and root Cl(-) concentration in the more salt-sensitive 'Koroneiki'. Na(+) and Cl(-) accumulation was associated with the lower water use in 'Koroneiki' but not in 'Picual'. Although eCO(2) increased WUE in salinized leaves and decreased salt ion uptake in the relatively salt-tolerant 'Koroneiki', growth of these young olive trees was not affected by eCO(2). PMID- 17728015 TI - Pulmonary colonization with Salmonella enterica serovar Kentucky in an intensive care unit. PMID- 17728016 TI - Contribution of tap water to patient colonisation with Pseudomonas aeruginosa in a medical intensive care unit. AB - This study examined tap water as a source of Pseudomonas aeruginosa in a medical intensive care setting. We prospectively screened specimens of patients, tap water and hands of healthcare workers (HCWs) over a six-month period in a 16-bed medical intensive care unit. Molecular relatedness of P. aeruginosa strains was investigated by pulsed-field gel electrophoresis. A total of 657 tap water samples were collected from 39 faucets and 127 hands of HCWs were sampled. P. aeruginosa was found in 11.4% of 484 tap water samples taken from patients' rooms and in 5.3% of 189 other tap water samples (P<0.01). P. aeruginosa was isolated from 38 patients. Typing of 73 non-replicate isolates (water samples, hands of HCWs and patients) revealed 32 major DNA patterns. Eleven (52.4%) of the 21 faucets were contaminated with a patient strain, found before isolation from tap water in the corresponding room in nine cases, or from the neighbouring room in two cases. Among seven P. aeruginosa strains isolated from HCW hands, the genotype obtained was the same as that from the last patient they had touched in six cases, and in the seventh with the last tap water sample used. More than half of P. aeruginosa carriage in patients was acquired via tap water or cross transmission. Carriage of P. aeruginosa by patients was both the source and the consequence of tap water colonisation. These results emphasise the need for studies on how to control tap water contamination. PMID- 17728017 TI - alpha-Latrotoxin affects mitochondrial potential and synaptic vesicle proton gradient of nerve terminals. AB - Ca(2+)-independent [(3)H]GABA release induced by alpha-latrotoxin was found to consist of two sequential processes: a fast initial release realized via exocytosis and more delayed outflow through the plasma membrane GABA transporters [Linetska, M.V., Storchak, L.G., Tarasenko, A.S., Himmelreich, N.H., 2004. Involvement of membrane GABA transporters in alpha-latrotoxin-stimulated [(3)H]GABA release. Neurochem. Int. 44, 303-312]. To characterize the toxin stimulated events attributable to the transporter-mediated [(3)H]GABA release from rat brain synaptosomes we studied the effect of alpha-latrotoxin on membrane potentials and generation of the synaptic vesicles proton gradient, using fluorescent dyes: potential-sensitive rhodamine 6G and pH-sensitive acridine orange. We revealed that alpha-latrotoxin induced a progressive dose-dependent depolarization of mitochondrial membrane potential and an irreversible run-down of the synaptic vesicle proton gradient. Both processes were insensitive to the presence of cadmium, a potent blocker of toxin-formed transmembrane pores, indicating that alpha-latrotoxin-induced disturbance of the plasma membrane permeability was not responsible to these effects. A gradual dissipation of the synaptic vesicle proton gradient closely coupled with lowering the vesicular GABA transporter activity results in a leakage of the neurotransmitter from synaptic vesicles to cytoplasm. As a consequence, there is an essential increase in GABA concentration in a soluble cytosolic pool that appears to be critical parameter for altering the mode of the plasma membrane GABA transporter operation from inward to outward. Thus, our data allow clarifying what cell processes underlain a recruitment of the plasma membrane transporter-mediated pathway in alpha-LTX stimulated secretion. PMID- 17728019 TI - Attracting students to aged care: the impact of a supportive orientation. AB - INTRODUCTION: The 'Building connections in aged care' project sought to investigate quality clinical placements for undergraduate nursing students in residential aged care facilities in Tasmania, Australia. BACKGROUND: Aged care reportedly holds little attraction to student nurses as an employment option, exacerbating problems with recruiting staff into the sector. This, coupled with knowing the quality of an undergraduate learning experience can influence career choices, provided the impetus for the study. METHODS: Informed by action research and conducted in three-stages, the project scoped the problem, implemented improvement strategies and assessed sustainability of their effectiveness. Data were collected via structured research meetings and surveys/check lists, and subjected to qualitative and quantitative analysis. RESULTS: A key finding was the importance of providing students with a comprehensive orientation to the aged care environment. DISCUSSION: The critical nature of orientation processes in the establishment of a supportive and welcoming environment for students, and to 'setting up' a positive and enjoyable learning experience in aged care settings has not been shown by research to date. CONCLUSION: Student orientation warrants greater attention. We recommend strategies concerning the structure of student orientation programs, links with university schools of nursing, use of preceptors, and preparing aged care facility staff. PMID- 17728018 TI - PS2 protein expression is upregulated by sex steroids in the cerebral cortex of aging mice. AB - Mutations in presenilin (PS) genes cause majority of early onset Alzheimer's disease (AD), an age related neurodegenerative disorder. PS proteins undergo proteolytic cleavage to produce biologically active fragments, which constitute the catalytic core of the gamma-secretase enzyme. This enzyme cleaves beta amyloid precursor protein (betaAPP) to generate Abeta peptides, which are influenced by sex steroids. Recently we have reported the downregulation of PS1 expression by sex steroids in the brain of adult mice. Here we have examined the effect of gonadectomy and subsequent administration of gonadal hormones 17beta estradiol and testosterone on the level of PS2 C-terminal fragment (CTF) in the cerebral cortex of adult and old AKR strain mice of both sexes. PS2 expression was downregulated following gonadectomy, but upregulated by supplementation of gonadal steroids in both age groups and sexes. Thus these results demonstrate up regulation of PS2 protein expression by sex steroids, which in turn may influence PS2 associated brain functions. PMID- 17728020 TI - Antigenic differentiation of classical swine fever vaccinal strain PAV-250 from other strains, including field strains from Mexico. AB - Twenty-nine classical swine fever virus (CSFv) strains were grown in the PK15 or SK6 cell lines. Antigenic differentiation studies were performed using monoclonal antibodies (McAbs), produced at Lelystad (CDI-DLO), The Netherlands. The monoclonals which were classified numerically as monoclonals 2-13. Epitope map patterns that resulted from the reactivity with McAbs were found to be unrelated to the pathogenicity of the viruses studied. Antigenic determinants were recognized by McAbs 5 and 8, were not detected in some Mexican strains; however, sites for McAb 6 were absent in all strains. The PAV-250 vaccine strain was recognized by all MAbs, except by MAb 6. Furthermore, the Chinese C-S vaccine strain was found to be very similar to the GPE(-) vaccine. None of the studied Mexican vaccines or field strains was found to be similar to the PAV-250 vaccine strain. PMID- 17728021 TI - Inhibition effects on liver tumors of BALB/c mice bearing H22 cells by immunization with a recombinant immunogen of GnRH linked to heat shock protein 65. AB - In the following study, we prepared a double-chain miniprotein with each chain containing three linear repeats of the self-peptide gonadotropin-releasing hormone (GnRH(3)), the hinge region of human IgG1 (hinge), and a T-helper epitope from the measles virus protein (MVP). The di-GnRH(3)-hinge-MVP miniprotein was conjugated to purified recombinant heat shock protein 65 (Hsp65) of Mycobacterium bovis and used to immunize BALB/c mice primed with subcutaneous injection of Bacillus Calmette-Gurerin (BCG) in the absence of adjuvants. After anti-GnRH antibodies were successfully produced, mice were inoculated with H22 cells as a solid tumor. The results showed that after GnRH was inhibited by anti-GnRH antibodies the testosterone levels in sera markedly decreased (P<0.01) and the testicle weights reduced as well (P<0.05) in GnRH(3)-hinge-MVP-Hsp65-immunized mice. The average weight of tumors in mice treated with GnRH(3)-hinge-MVP-Hsp65 was significantly lower than in mice treated with saline only (neutral control, P<0.001), or less than in mice treated with Hsp65 (negative control, P<0.005). The data reported here demonstrated that GnRH(3)-hinge-MVP-Hsp65 could significantly attenuate the progression of liver tumor in mice transplanted with H22 cells, and might develop to be palliative treatment of hepatocellular carcinoma (HCC) patients in the future. PMID- 17728022 TI - Advances in immunology and vaccine discovery report of the United States-European Commission workshop. AB - As the 21st century unfolds, infectious diseases remain one of the most significant threats to our economy, our food animal production systems, animal welfare, and most importantly, the lives of people worldwide, regardless of their economic standing. The potential use of biological threat agents for terrorism or biowarfare further undermines the security of our society. Arguably, vaccines represent the single most cost-effective, medically delivered strategy for confronting these challenges. The workshop "Advances in Immunology and Vaccine Discovery" was organized to address these challenges, based on the conviction that the interface between immunology and vaccinology offers the best prospects for major breakthroughs in vaccine discovery and development. Six focus areas were identified by workshop organizers: (1) pathogen immune evasion; (2) innate immunity; (3) mucosal immunity; (4) immunogenetics; (5) comparative immunology; and (6) genomics. These areas provided opportunities to elucidate how protective immunity may relate to the disruption of the molecular mechanisms that underlie host-pathogen interactions. A report generated by workshop organizers and participants provides key recommendations and identifies important research gaps, needs, future steps, and potential strategic US-EU collaborations. The report is available on line through ScienceDirect (URL). PMID- 17728023 TI - Long lasting BCG protection against leprosy. AB - BACKGROUND: BCG vaccine protects against leprosy. OBJECTIVES: Estimate BCG protection against leprosy by age by age. METHODS: A case control study with 226 cases of leprosy and 857 controls. BCG vaccination was ascertained via examination of BCG scars. Protection is presented for three age groups. RESULTS: BCG protection against leprosy was 86% (95% CI: 77-92%) in the age group 18-29; 54% (95% CI: -37% to 85%) in the age group 30-39 and 32% (95% CI: -3% to 56%) in those aged 40 or more. CONCLUSIONS: BCG efficacy against leprosy may well last for three decades and possibly even longer. BCG vaccination must have contributed to worldwide reduction in leprosy incidence. PMID- 17728024 TI - Partial protection against H5N1 influenza in mice with a single dose of a chimpanzee adenovirus vector expressing nucleoprotein. AB - The development of adenoviral vectors based on non-human serotypes such as the chimpanzee adenovirus simian adenovirus 24 (AdC7) may allow for their utilization in populations harboring neutralizing antibodies to common human serotypes. Because adenoviral vectors can be used to generate potent T cell responses, they may be useful as vaccines against pandemic influenza such as may be caused by the H5N1 strains that are currently endemic in avian populations. The influenza nucleoprotein (NP) is known to provide MHC Class I restricted epitopes that are effective in evoking a cytolytic response. Because there is only low sequence variation in NP sequences between different influenza strains, a T cell vaccine may provide heterosubtypic protection against a spectrum of influenza A strains. An AdC7 vector expressing the influenza A/Puerto Rico/8/34 NP was tested for its efficacy in protecting BALB/c mice against two H5N1 strains and compared to a conventional human adenovirus serotype 5 vaccine. The AdC7 NP vaccine elicited a strong anti-NP T cell response. When tested in a mouse challenge model, there was improved survival following challenge with two strains of H5N1 that have caused human outbreaks, Vietnam/1203/04 and Hong Kong/483/97, although the improved survival reached statistical significance only with the strain from Vietnam. PMID- 17728025 TI - Role of U.S. military research programs in the development of U.S.-licensed vaccines for naturally occurring infectious diseases. AB - U.S. military physicians and researchers have collaborated in the development of eight U.S.-licensed vaccines since 1934, when product efficacy requirements were added to product safety requirements mandated in 1902. These vaccines include influenza (1945), rubella (1969), adenovirus types 4 and 7 (1980), meningococcus A, C, Y, W-135 (1981), hepatitis B (1981), oral typhoid (1989), Japanese encephalitis (1992), and hepatitis A (1995). Current efforts include new adenovirus and Japanese encephalitis vaccines, and vaccines to prevent dengue, diarrhea due to enterotoxigenic E. coli, Campylobacter, and Shigella, malaria, hemorrhagic fever with renal syndrome, scrub typhus, meningococcus type B, and HIV infection. All vaccines currently administered to U.S. military forces must be licensed by the U.S. Food and Drug Administration (FDA). PMID- 17728026 TI - In vivo tissue distribution and kinetics of a pseudorabies virus plasmid DNA vaccine after intramuscular injection in swine. AB - Previous biodistribution studies of plasmids following intramuscular or intradermal injections of DNA vaccines have been performed in mice, rats or rabbits, but not in large mammals. The aim of the present study was to determine the biodistribution of plasmids in swine using the PRV-specific DNA vaccination model consisting of a single intramuscular (i.m.) injection of three plasmids individually encoding glycoproteins gB, gC and gD. The weak bioavailability of the plasmids (less than 10%) after i.m. injection was consistent with the tissue distribution study. Plasmids remained in the injected muscle for at least 4 weeks and were also detected in liver, spleen, kidney, lung, remote muscle, lymph nodes and ovaries for shorter periods. Differences in persistence, apparent elimination half-lives and clearance in blood were observed between the three plasmids. In conclusion, the three plasmids behaved differently and were transiently detected in most of the organs tested. The exact persistence in the injected muscle was not determined but exceeded 4 weeks. To date this is the first published DNA vaccine tissue distribution study in large animals. PMID- 17728028 TI - 137Cs and 90Sr transfer to milk in Austrian alpine agriculture. AB - The alpine regions of Austria were among the most contaminated territories outside of the former USSR after the Chernobyl accident. In the investigated province of Salzburg the median (137)Cs surface deposition was 31.4 kBq m(-2) with maximum values exceeding 90 kBq m(-2) (May 1986). To quantify the transfer of (137)Cs and (90)Sr from vegetation to milk in these seminatural conditions nine seasonally grazed alps were identified and vegetation and milk sampled during summer 2002 and summer 2003. Mean+/-SD milk transfer coefficients (fm) for (137)Cs and (90)Sr were 0.0071+/-0.0009 d l(-1), and 0.0011+/-0.0004 d l(-1), respectively; which for (137)Cs is markedly higher than those fm values found in intensive agricultural systems. Transfer kinetics for (137)Cs into cow milk were approximated using a 2-compartment model with a short and a long-term component. Fitting the model to empirical data results in reliable estimates of the time constant of the short-term component, biological half-life 1.06+/-0.28 d, whereas the estimates of the long-term component are subject to high uncertainties. PMID- 17728027 TI - Review of Russian language studies on radionuclide behaviour in agricultural animals: part 1. Gut absorption. AB - An extensive programme of experiments was conducted in the former USSR on transfer of radionuclides to a wide range of different agricultural animals. Only a few of these studies were made available in the English language literature or taken into account in international reviews of gastrointestinal uptake. The paper gives extended information on Russian research on radionuclide absorption in the gut of farm animals performed in controlled field and laboratory experiments from the 1960s to the current time. The data presented in the paper, together with English language values, will be used to provide recommended values of absorption specifically for farm animals within the revision of the IAEA Handbook of Parameter Values IAEA [International Atomic Energy Agency, 1994. Handbook of Parameter Values for the Prediction of Radionuclide Transfer in Temperate Environments, IAEA technical reports series No. 364. International Atomic Energy Agency, Vienna]. PMID- 17728029 TI - Effect of flow-induced shear stress on migration of human trophoblast cells. AB - BACKGROUND: During the processes of placenta development, the migration of the trophoblast cells (TCs) is most likely affected by blood flow. This study was to examine the effect of flow-induced shear stress on the migration of the human TCs. METHODS: Using a flow chamber technique, steady-state flow shear stress was imposed on early gestation human TCs cultured on glass slides for up to 24h. The imposed shear stress levels in this study were 0, 7.5, 15, and 30dyn/cm(2), respectively. The motility of TCs under study was evaluated by quantitative analysis of the microscopy pictures captured. FINDINGS: The results showed that in the absence of flow, TCs were highly dynamic with constant non-directional positional shifts, but with no net cell migration. Exposure of the cells to shear stresses of 7.5, 15, 30dyn/cm(2) within 24h significantly increased the level of this activity and led to net cell migration in the direction of flow. INTERPRETATION: The results from the in vitro study demonstrated that shear stress regulated trophoblast motility, but did not induce the migration of TCs in the direction against flow stream like in the situation in vivo. Therefore the present study suggests that in vivo TC migration is most likely regulated not only by mechanical stimuli but by biochemical stimuli as well. PMID- 17728030 TI - ASB clinical biomechanics award winner 2006 prospective study of the biomechanical factors associated with iliotibial band syndrome. AB - BACKGROUND: Iliotibial band syndrome is the leading cause of lateral knee pain in runners. Despite its high prevalence, little is known about the biomechanics that lead to this syndrome. The purpose of this study was to prospectively compare lower extremity kinematics and kinetics between a group of female runners who develop iliotibial band syndrome compared to healthy controls. It was hypothesized that runners who develop iliotibial band syndrome will exhibit greater peak hip adduction, knee internal rotation, rearfoot eversion and no difference in knee flexion at heel strike. Additionally, the iliotibial band syndrome group were expected to have greater hip abduction, knee external rotation, and rearfoot inversion moments. METHODS: A group of healthy female recreational runners underwent an instrumented gait analysis and were then followed for two years. Eighteen runners developed iliotibial band syndrome. Their initial running mechanics were compared to a group of age and mileage matched controls with no history of knee or hip pain. Comparisons of peak hip, knee, rearfoot angles and moments were made during the stance phase of running. Variables of interest were averaged over the five running trials, and then averaged across groups. FINDINGS: The iliotibial band syndrome group exhibited significantly greater hip adduction and knee internal rotation. However, rearfoot eversion and knee flexion were similar between groups. There were no differences in moments between groups. INTERPRETATION: The development of iliotibial band syndrome appears to be related to increased peak hip adduction and knee internal rotation. These combined motions may increase iliotibial band strain causing it to compress against the lateral femoral condyle. These data suggest that treatment interventions should focus on controlling these secondary plane movements through strengthening, stretching and neuromuscular re-education. PMID- 17728031 TI - Specific accumulation of arsenic compounds in green turtles (Chelonia mydas) and hawksbill turtles (Eretmochelys imbricata) from Ishigaki Island, Japan. AB - Concentrations of total arsenic (As) and individual compounds were determined in green and hawksbill turtles from Ishigaki Island, Japan. In both species, total As concentrations were highest in muscle among the tissues. Arsenobetaine was a major compound in most tissues of both turtles. High concentrations of trimethylarsine oxide were detected in hawksbill turtles. A significant negative correlation between standard carapace length (SCL), an indicator of age, and total As levels in green turtles was found. In contrast, the levels increased with SCL of hawksbill turtles. Shifts in feeding habitats with growth may account for such a growth-dependent accumulation of As. Although concentrations of As in marine sponges, the major food of hawksbill turtles are not high compared to those in algae eaten by green turtles, As concentrations in hawksbill turtles were higher than those in green turtles, indicating that hawksbill turtles may have a specific accumulation mechanism for As. PMID- 17728032 TI - Trauma and medically unexplained symptoms towards an integration of cognitive and neuro-biological accounts. AB - Medically unexplained symptoms (MUS) are frequently associated with a history of traumatization. The first purpose of the present review paper was to investigate systematically the evidence for such relation in a subset of clinical samples with MUS presenting with functional somatization: chronic pelvic pain, irritable bowel syndrome and conversion and somatization disorder. The second purpose was to critically review three dominant models explaining the relation between trauma and MUS (i.e. dissociation, conversion and hierarchical cognitive models). The latter model in particular adequately accounts for the non-volitional and non intentional character of MUS and explains how traumata can affect the development of MUS without assuming that previous trauma is a necessary prerequisite of MUS. The cognitive model, however, lacks integration with current neurobiological findings, indicative of central stress-and central nervous system alterations in MUS. The final purpose of the present paper was, therefore, to review current neurobiological studies focused on trauma and MUS and to formulate a research agenda to integrate these neurobiological developments with cognitive models for MUS. PMID- 17728033 TI - Tobacco expenditures and child health and nutritional outcomes in rural Bangladesh. AB - This study examined the relationship between tobacco prices and child health outcomes so as to assess the potential of improved child health outcomes resulting from less tobacco expenditure. In part, this paper was motivated by a study by. Efroymson et al. [(2001). Hungry for tobacco: An analysis of the economic impact of tobacco consumption on the poor in Bangladesh. Tobacco Control, 10, 212-217] suggesting that for the poorest households in Bangladesh, amongst whom malnutrition is widespread, shifting tobacco expenditures to expenditures on food would significantly improve the nutritional status of the household. We used data from a survey of 956 households conducted in rural Bangladesh between June 1996 and September 1997. The households were surveyed four times at approximately 4-month intervals during the 16-month period. We restricted our sample to households with children aged 2-10, and 600 households satisfied this criterion. The primary dependent variables for this study are three anthropometric indicators of child health and nutritional status: a standardized measure of height for age, a standardized measure of weight for height, and a standardized measure of weight for age. We also used measures of self-reported morbidity, including the incidence and duration of respiratory illness. We used regression methods on data averaged across survey rounds to estimate the relationship between tobacco prices and the outcome variables. Tobacco prices were found to be a significant determinant of height for age and weight for height for both boys and girls. Furthermore, the price of tobacco products is a significant predictor of weight for age for girls and the pooled sample. Our results suggest that higher tobacco prices would, for the most part, improve child health. PMID- 17728034 TI - AMPA receptor involvement in 5-hydroxytryptamine2A receptor-mediated pre-frontal cortical excitatory synaptic currents and DOI-induced head shakes. AB - Glutamate plays an important role in the psychotomimetic effects of both channel blocking N-methyl D-aspartate (NMDA) receptor antagonists and hallucinogenic drugs which activate 5-hydroxytryptamine2A (5-HT2A) receptors. Previous work suggested that activation of non-NMDA ionotropic glutamate receptors mediates the effects of 5-HT-induced excitatory post-synaptic potentials/currents (EPSPs/EPSCs) when recording from layer V pyramidal cells in the rat medial pre frontal cortex (mPFC). However, those effects are mediated by either alpha-amino 3-hydroxy-5-methylisoxazole-4-propionate (AMPA) or kainate receptors of the iGluk5 subtype. To test whether activation of AMPA receptors is sufficient to mediate 5-HT-induced EPSCs, a 2,3-benzodiazepine that selectively blocks AMPA receptors was assessed. This selective AMPA receptor antagonist potently suppressed 5-HT-induced EPSCs. Since phenethylamine hallucinogens induce head shakes by activating 5-HT2A receptors in the mPFC and this action is modulated by glutamate, we also examined whether selective blockade of AMPA receptors would suppress DOI-induced head shakes. As predicted, we found that selective blockade of AMPA receptors suppressed DOI-induced head shakes. Given evidence that activation of AMPA receptors is an important downstream effect for both channel blocking NMDA receptor antagonists and phenethylamine hallucinogens, we also tested multiple doses of DOI with a sub-anesthetic dose of MK-801. Synergistic action between these two classes of psychotomimetic drugs was demonstrated by MK 801 enhancing DOI-induced head shakes and locomotor activity. These findings expand the dependence of both channel blocking NMDA receptor antagonists and phenethylamine hallucinogens on enhancing extracellular glutamate. PMID- 17728035 TI - No enhancing effects of diacylglycerol oil on tumor development in a medium-term multi-organ carcinogenesis bioassay using male F344 rats. AB - The modifying potential of diacylglycerol (DAG) oil on tumor development was investigated in a medium-term multi-organ carcinogenesis bioassay. DAG oil is a cooking oil that contains >80% diglycerides, <20% triglycerides and <5% monoglycerides. Male 6-week-old F344 rats (20 in each group) were sequentially treated with five carcinogens for initiation in different organ target sites for 4 weeks (DMBDD treatment), and then administered DAG oil at dietary levels of 0% (control), 1.375%, 2.75% or 5.5% [triacylglycerol (TGs), with the same fatty acid composition as DAG oil were also added at dietary levels of 5.5%, 4.125%, 2.75% and 0%, respectively, to maintain the same lipid level], or 5.5% high linoleic acid TG (HLTG), 5.5% high oleic acid TG (HOTG), or 5.5% medium-chain TG (MCTG) (as reference substances, mostly consisting of triacylglycerols) admixed into AIN 93G semi-synthetic diet, for an additional 24 weeks. Controls received standard diet without any supplementation as non-treated control. All animals were killed at the end of week 28, and the major organs were carefully examined for preneoplastic and neoplastic lesions. No DAG oil treatment-related changes were noted in survival, general conditions, body weights, food consumption and organ weights. Upon quantitative analysis of glutathione S-transferase placental form (GST-P) positive foci of the liver, DAG oil was not found to exert any effects. The incidence of colon adenomas was significantly increased in rats given 1.375% DAG oil, but not 2.75% and 5.5% DAG oil, when compared to the control (5.5% TG group) value. Furthermore, incidences and multiplicity of hyperplasias and adenomas and/or adenocarcinomas were comparable across all DAG oil-treated groups. In contrast, incidences of colon adenomas and/or adenocarcinomas were significantly increased in rats given 5.5% HOTG, and adenomas with MCTG, but not 5.5% HLTG, as compared to the 5.5% TG value. Preneoplastic and neoplastic lesions induced by DMBDD treatment in various organs other than the large intestine were comparable in all cases. Thus, the current results indicate that DAG oil may not exert modifying potential on tumor development, even in the colon because of the lack of dose-dependence. DAG oil was equivalent to HOTG (standard cocking oil composed of naturally occurring fatty acids), with regard to colon tumor development. Further dose-response study concerning HOTG may be needed to confirm whether the enhancing effect of large intestine carcinogenesis exert or not. PMID- 17728036 TI - [Composite tissues allotransplantation (CTA). Preface]. PMID- 17728037 TI - Nephrotoxicity induced by the R- and S-enantiomers of N-(3,5-dichlorophenyl)-2 hydroxysuccinimide (NDHS) and their sulfate conjugates in male Fischer 344 rats. AB - The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) induces nephrotoxicity characterized as polyuric renal failure and mediated via metabolites arising from oxidation of the succinimide ring. Recent findings have suggested that the stereochemical nature of NDPS metabolites may be an important factor in NDPS metabolite-induced nephrotoxicity. The purpose of the present study was to determine the role of stereochemistry in the in vivo nephrotoxicity induced by R-(+)- and S-(-)-N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (R- and S NDHS) and the in vitro nephrotoxicity induced by their enantiomeric sulfate conjugates, R-(-)- and S-(+)-N-(3,5-dichlorophenyl)-2-hydroxysuccinimide-O sulfate (R- and S-NSC). Male Fischer 344 rats (four rats/group) were administered intraperitoneally (i.p.) an enantiomer of NDHS (0.05, 0.1 or 0.2 mmol/kg) or vehicle, and renal function monitored for 48 h. R-NDHS (0.1 or 0.2 mmol/kg) had little effect on renal function. In contrast, S-NDHS (0.1 mmol/kg) induced marked nephrotoxicity. The nephrotoxic potential of R- and S-NSC (0.5, 0.75 or 1.0mM) was determined using freshly isolated rat renal cortical cells (IRCC, 3-4 x 10(6)cells/ml). Cytotoxicity was determined by measuring the release of lactate dehydrogenase (LDH) at the end of a 1h incubation period. The LDH release observed in these studies was similar between R- and S-NSC. These results indicate that stereochemistry is an important factor for NDPS metabolite nephrotoxicity and that the role of stereochemistry, at least for NSC, occurs at extra-renal sites. PMID- 17728038 TI - Telomere instability and cancer. AB - Telomeres are required to preserve genome integrity, chromosome stability, nuclear architecture and chromosome pairing during meiosis. Given that telomerase activity is limiting or absent in most somatic tissues, shortening of telomeres during development and aging is the rule. In vitro, telomere length operates as a mechanism to prevent uncontrolled cell growth and therefore defines the proliferation potential of a cell. In vitro, in somatic cells that have lost proliferation control, shortening of telomeres becomes the main source of genome instability leading to genetic or epigenetic changes that may allow cells to become immortal and to acquire tumor phenotypes. In vivo, mice models have indisputably shown both the protective and the promoting role of very short telomeres in cancer development. In humans, although telomere shortening and other types of telomere dysfunction probably contribute to the genome instability often detected in tumors, the specific contributions of such instability to the development of cancer remain largely undetermined. PMID- 17728039 TI - Quality of cardiopulmonary resuscitation before and during transport in out-of hospital cardiac arrest. AB - AIM OF THE STUDY: To evaluate quality of cardiopulmonary resuscitation (CPR) performed during transport after out-of-hospital cardiac arrest. MATERIALS AND METHODS: Retrospective, observational study of all non-traumatic cardiac arrest patients older than 18 years who received CPR both before and during transport between May 2003 and December 2006 from the community run EMS system in Oslo. Chest compressions and ventilations were detected from impedance changes in routinely collected ECG signals, and hands-off ratio calculated as time without chest compressions divided by total CPR time. RESULTS: Seventy-five of 787 consecutive out-of-hospital cardiac arrest patients met the inclusion criteria. Quality data were available from 36 of 66 patients receiving manual CPR and 7 of 9 receiving mechanical CPR. CPR was performed for mean 21+/-11 min before and 12+/-8 min during transport. With manual CPR hands-off ratio increased from 0.19+/-0.09 on-scene to 0.27+/-0.15 (p=0.002) during transport. Compression and ventilation rates were unchanged causing a reduction in compressions per minute from 94+/-14 min(-1) to 82+/-19 min(-1) (p=0.001). Quality was significantly better with mechanical than manual CPR. Four patients (5%) survived to hospital discharge; two with manual CPR (Cerebral performance categories (CPC) 1 and 2), and two with mechanical CPR (CPC scores 3 and 4). No discharged patients had any spontaneous circulation during transport. CONCLUSIONS: The fraction of time without chest compressions increased during transport of out-of-hospital cardiac arrest patients. Every effort should therefore be made to stabilise patients on scene before transport to hospital, but all transport with ongoing CPR is not futile. PMID- 17728040 TI - Out-of-hospital thrombolysis during cardiopulmonary resuscitation in patients with high likelihood of ST-elevation myocardial infarction. AB - Up to 90% of cardiac arrests are due to acute myocardial infarction or severe myocardial ischaemia. Thrombolysis is an effective treatment for ST-elevation myocardial infarction (STEMI), but there is no evidence or guideline to put forward a thrombolysis strategy during cardiopulmonary resuscitation (CPR). In two physician-manned emergency medical service (EMS) units in Berlin, Germany, using thrombolysis is based on an individual judgment of the EMS physician managing the CPR attempt. In this retrospective analysis over 3 years (total 22.164 scene calls), thrombolysis was started at the scene in 50 patients during brief intermittent phases of spontaneous circulation, and in 3 patients during ongoing CPR. On-scene diagnosis of myocardial infarction was established in 45 patients (85%) by a 12-lead ECG, 5 (9%) patients had a left bundle branch block. Sixteen patients (30%) died at the scene, 37 patients (70%) were admitted to a hospital. In-hospital mortality was 35% (13 of 37 patients), with cause of death being cardiogenic shock in nine patients, hypoxic cerebral coma in two and acute haemorrhage in two other patients. All 24 of 53 (45%) survivors were discharged with an excellent neurological recovery. CPR was started by an EMS physician in 18 of the 24 survivals (75%) and emergency medical technicians who arrived first in six (25%). Duration of CPR until return of spontaneous circulation was <10 min in 13 of 24 (54%) of the survivors. Thrombolysis was initiated during intermittent phases of spontaneous circulation in 50 (94%) of all patients and in 23 (96%) of the 24 survivors. In conclusion, this retrospective analysis shows excellent survival rates and neurological outcome in selected patients with a high likelihood of myocardial infarction, who develop cardiac arrest and are treated with thrombolysis. PMID- 17728041 TI - Exclusion of a patient assessment interval and extension of the CPR interval both mitigate post-resuscitation myocardial dysfunction in a swine model of cardiac arrest. AB - AIM OF STUDY: Interruptions in cardiopulmonary resuscitation (CPR), particularly as guided by automated external defibrillators, have been implicated in poor survival from cardiac arrest. Interruptions of CPR may be reduced by eliminating repetition of shocks between periods of CPR, elimination of the interval for patient assessment before CPR, and extension of the periods of CPR. MATERIALS AND METHODS: The effects of exclusion of a 30s post-shock assessment interval prior to CPR and use of a longer interval (180s versus 90s) of CPR on resuscitation and post-resuscitation function were assessed in a factorial design using an established swine model of cardiac arrest. Repetitive shocks were excluded. Ventricular fibrillation was induced ischemically and maintained untreated for 5min. RESULTS: All subjects were resuscitated, 95% survived 3 days, and 97% of survivors had full neurological recovery. Exclusion of the assessment interval reduced the delay to first return of spontaneous circulation by 33.1s (P=0.004) and the delay to sustained resuscitation by 99.2s (P=0.004), reduced post resuscitation ECG ST elevation by 0.12mV (P=0.03), and alleviated transient post resuscitation ejection fraction reduction (P<0.0001). Extension of the CPR interval reduced transient post-resuscitation fractional area change impairment (P=0.003). CONCLUSIONS: Exclusion of an interval for assessment of airway, breathing and signs of circulation mitigates post-resuscitation dysfunction in a swine model of cardiac arrest. Extension of the period of CPR independently provides measurable, though less comprehensive, mitigation as well. PMID- 17728042 TI - Soluble epoxide hydrolase gene deletion reduces survival after cardiac arrest and cardiopulmonary resuscitation. AB - The P450 eicosanoids epoxyeicosatrienoic acids (EETs) are produced by cytochrome P450 arachidonic acid epoxygenases and metabolized through multiple pathways, including soluble epoxide hydrolase (sEH). Pharmacological inhibition and gene deletion of sEH protect against ischemia/reperfusion injury in brain and heart, and against hypertension-related end-organ damage in kidney. We tested the hypothesis that sEH gene deletion improves survival, recovery of renal function and pathologic ischemic renal damage following transient whole-body ischemia induced by cardiac arrest (CA) and resuscitation. Mice with targeted deletion of sEH (sEH knockout, sEHKO) and C57Bl/6 wild-type control mice were subjected to 10 min CA, followed by cardiopulmonary resuscitation (CPR). Survival in wild-type mice was 93% and 80% at 10 min and 24 h after CA/CPR (n=15). Unexpectedly, survival in sEHKO mice was significantly lower than WT. Only 56% of sEHKO mice survived for 10 min (n=15, p=0.014 compared to WT) and no mice survived for 24 h after CA/CPR (p<0.0001 versus WT). We conclude that sEH plays an important role in cardiovascular regulation, and that reduced sEH levels or function reduces survival from cardiac arrest. PMID- 17728043 TI - Factors associated with survival in children with traumatic cardiopulmonary arrest. PMID- 17728044 TI - Miniaturized mechanical chest compressor: a new option for cardiopulmonary resuscitation. AB - AIM OF STUDY: After cardiac arrest, uninterrupted chest compressions with restoration of myocardial blood flow facilitates restoration of spontaneous circulation. We recognized that this may best be accomplished with a mechanical device and especially so during transport. We therefore sought to develop a lightweight, portable chest compressor which may be carried on the belt or attached to the oxygen tank typically carried on the back of the first response rescuer. A miniaturized pneumatic chest compressor (MCC) weighing less than 2 kg was developed and compared with a currently marketed "Michigan Thumper", which weighed 19 kg. We hypothesized that the 2 kg, low profile, portable device will be as effective as the standard pneumatic Thumper for restoring circulation during CPR. MATERIAL AND METHODS: Ventricular fibrillation was electrically induced in 10 domestic male pigs weighing 39+/-2 kg, and untreated for 5 min. Animals were then randomized to receive chest compressions with either the MCC or the Thumper. After 5 min of mechanical chest compression, defibrillation was attempted with a 150 J biphasic shock. Coronary perfusion pressure (CPP) and end tidal PCO(2) (EtPCO(2)) were measured by conventional techniques together with right carotid artery blood flow (CBF). RESULTS: Four of five animals compressed with the Thumper and each animal compressed with the MCC were successfully resuscitated. No significant differences in CPP, EtPCO(2), CBF and post resuscitation myocardial function were observed between groups. Resuscitated animals survived for more than 72 h without neurological impairment. CONCLUSION: The low profile, 2 kg miniaturized chest compressor is as effective as the conventional Thumper in an experimental model of CPR. PMID- 17728045 TI - Evaluation of a simplified therapeutic intervention scoring system (TISS-28) and the modified early warning score (MEWS) in predicting physiological deterioration during inter-facility transport. AB - INTRODUCTION: There is an emerging demand for inter-facility transport (IFT) of patients in recent years following changes in the healthcare framework in Hong Kong but this carries certain risks. Anticipation of possible deterioration of patients is important for patient safety and therefore risk stratification of patients before transport is important. OBJECTIVE: This study evaluated the simplified therapeutic intervention scoring system (TISS-28) and modified early warning score (MEWS) in predicting physiological deterioration en route. METHODS: This is a prospective single centre study of all emergency IFT for adult patients, excluding patients with obstetric conditions, occurring between 1 January 2005 and 30 June 2006. The severity of illness was quantified in terms of TISS-28 and MEWS. Mann-Whitney test and receiver operator characteristic (ROC) curves were used to illustrate and compare their performance. RESULTS: Among 102 patients requiring IFT, 28 had physiological deterioration en route (27%). The TISS-28 scores upon dispatch ranged from 5 to 34 with a mean of 16.5+/-5.71 whereas MEWS ranged from 0 to 11 with a mean of 2.82+/-2.01. The incidence of physiological deterioration en route was significantly greater with a higher MEWS score (P=0.001) but this was not seen with the TISS-28 score. The area under the ROC curve for the predictive value of MEWS was 0.71 which performed better than TISS-28 (area under the curve=0.53). CONCLUSION: IFT represents a group of patients with vast heterogeneity. TISS-28 is not a useful tool for risk stratification prior to transport. MEWS was able to identify patients at risk but was not ideal. PMID- 17728046 TI - Assessing the level of consciousness in children: a plea for the Glasgow Coma Motor subscore. AB - AIM: The Glasgow Coma Scale (GCS) is not always easy to score and its reliability has been questioned. In adults the GCS Motor score has proven a valuable alternative, as it is easier to assess yet shows similar predictive capacity for outcome. We wanted to test the non-inferiority of the Glasgow Coma Motor score GCS-M versus the Total score GCS-T for predicting outcome in children. MATERIALS AND METHODS: As part of the Flemish paediatric trauma registry (PENTA) we collected data on 96 consecutive children (0-18 years) with moderate to severe traumatic brain injury. Outcome was evaluated using a three level ordinal scale: [normal to mild disability, moderate to severe disability and death]. A number of proportional odds models were fitted for various choices of predictive variables (GCS-T, GCS-M, age, sex, and injury severity score ISS). For each model we calculated Somers'D(xy) rank correlation and NagelKerke's R(2)N index, both measures of the predictive performance of the model. RESULTS: All children had an injury to the brain that resulted in a hospital stay of more than 48h. Half of them had a "best" initial GCS of 15; 60%, a Motor score of 6. The median Injury Severity Score ISS was 16. Outcome was 'normal to mild' in 79 children, 'moderate to severe' in 7, and 'death' in 10. D(xy) values were 0.983 for the model with the Motor score and 0.972 for that with the total GCS, indicating excellent predictive performance for both. R(2)N indices were 0.862 and 0.813, respectively. Overall the difference between all models was small. CONCLUSION: The GCS Motor subscore was shown to have at least the same predictive ability for outcome as the total GCS. It is our opinion that the total GCS is unnecessarily complicated (especially in children). Using the Motor score alone will improve scoring compliance and statistical performance. We do not believe that the reduction in number of potential scores from 13 to 6 would decrease the descriptive capacity significantly, since clinical algorithms typically group values of the total GCS into five or fewer ranges. PMID- 17728047 TI - The effects of cortisol administration on approach-avoidance behavior: an event related potential study. AB - We investigated the effects of cortisol administration (50 mg) on approach and avoidance tendencies in low and high trait avoidant healthy young men. Event related brain potentials (ERPs) were measured during a reaction time task, in which participants evaluated the emotional expression of photographs of happy and angry faces by making an approaching (flexion) or avoiding (extension) arm movement. The task consisted of an affect-congruent (approach happy faces and avoid angry faces) and an affect-incongruent (reversed instruction) condition. Behavioral and ERP analyses showed that cortisol enhanced congruency effects for angry faces in highly avoidant individuals only. The ERP effects involved an increase of both early (P150) and late (P3) positive amplitudes, indicative of increased processing of the angry faces in high avoidant subjects after cortisol administration. Together, these results suggest a context-specific effect of cortisol on processing of, and adaptive responses to, motivationally significant threat stimuli, particularly in participants highly sensitive to threat signals. PMID- 17728048 TI - Open to debate. The motion: PDE5 inhibitors will have a significant role in the treatment of BPH. PMID- 17728049 TI - Dorsal onlay skin graft bulbar urethroplasty: long-term follow-up. AB - OBJECTIVES: To report retrospectively long-term follow-up in a homogeneous group of patients who underwent dorsal onlay skin graft bulbar urethroplasty and to investigate which factors might influence long-term outcome. METHODS: Thirty eight patients, with an average age of 43 yr, underwent dorsal onlay skin graft (#12 ventral penile skin and #26 preputial mucosa) bulbar urethroplasty from 1994 to 2000. Of 38 patients, 23 (60.5%) had undergone prior endoscopic procedures. Preoperative evaluation included clinical history, physical examination, retrograde and voiding urethrography, and urethral sonography. Three weeks after surgery, voiding cystourethrography was performed. Patients were followed-up with a clinical evaluation and specific diagnostic tests every 4 mo in the first year and every 12 mo thereafter. Clinical outcome was considered a failure when postoperative instrumentation, including dilation, was needed. RESULTS: Average follow-up was 111 mo (range, 80-149). Of 38 cases, 25 (65.8%) were successful and 13 (34.2%) failures. Patients with stricture length > 6 cm and a previous history of urethrotomies or dilatations seemed to have a higher risk of failure, but this observation was only a trend and did not reach levels of statistical significance. CONCLUSIONS: Penile skin used as dorsal onlay graft for bulbar urethral reconstruction in a homogeneous series of patients showed a success rate ranging from 90% at short-term follow-up to 66% after long-term follow-up. There was no evidence for particular risk factors (length of stricture, number of dilatations and urethrotomies) for failure. PMID- 17728050 TI - The role of phosphodiesterase type 5 inhibitors in the management of premature ejaculation: a critical analysis of basic science and clinical data. AB - OBJECTIVES: To assess the usefulness of the phosphodiesterase type 5 inhibitors (PDE5-Is) in the treatment of premature ejaculation (PE) and to describe possible mechanisms to explain their effect. METHODS: A MedLine search was performed for peer-reviewed articles on the role of PDE5-Is in managing PE. No meta-analysis method was used. RESULTS: Five manuscripts that examined the efficacy of PDE5-Is in the treatment of PE were retrieved. Three studies used sildenafil as monotherapy and two used it in combination with a serotonin selective reuptake inhibitor (SSRI). Three studies demonstrated a beneficial effect of sildenafil in the treatment of PE, as measured by intravaginal ejaculatory latency time (IELT) and by different questionnaires assessing the patients' subjective feelings of ejaculatory control, sexual satisfaction, and anxiety. One study showed the superiority of sildenafil compared to other modalities. Two studies showed that combination therapy of paroxetine and sildenafil was better than paroxetine alone. One study did not demonstrate a beneficial effect of sildenafil in prolonging IELT, but showed that sildenafil improved patients' perception of ejaculatory control. Another study showed that topical anesthetics were better than sildenafil in the treatment of PE but did not use IELT or a validated questionnaire to measure the efficacy of treatment. Several possible mechanisms could explain effectiveness of the PDE5-Is for treatment of PE: centrally, through the effect on the nitric oxide/cyclic guanosine monophosphate pathway; peripherally by causing relaxation of smooth muscle in the vas deferens, seminal vesicles, prostate, and urethra and inhibition of adrenergic transmission; or locally by inducing peripheral analgesia. Another possibility might be prolongation of the duration of erection. CONCLUSIONS: Encouraging evidence supports the role of PDE5-Is for treating PE. Possible therapeutic mechanisms of action of PDE5-Is are multiple and complex and include central and peripheral effects. A large population, multicenter, randomized, double-blind, placebo controlled study is needed to elucidate the efficacy of PDE5-Is in the treatment of PE. PMID- 17728051 TI - Editorial comment on: TVT-O for the treatment of female stress urinary incontinence: results of a prospective study after a 3-year minimum follow-up. PMID- 17728052 TI - TVT-O for the treatment of female stress urinary incontinence: results of a prospective study after a 3-year minimum follow-up. AB - OBJECTIVES: Medium-term results of transobturator tapes for the treatment of female stress urinary incontinence (SUI) are largely unknown. We analyzed the 3 yr results of a prospective, observational study designed to evaluate the safety and efficacy of the TVT-O procedure. METHODS: Preoperative and postoperative evaluations included physical examination, uroflowmetry and postvoid residual (PVR) measurement, and urinary symptoms and quality of life (QoL) questionnaires. Data were compared by means of the Wilcoxon matched pairs test. RESULTS: Between March 2003 and December 2003, 102 consecutive patients with clinical and urodynamic diagnoses of SUI who fulfilled inclusion and exclusion criteria underwent the TVT-O procedure; the latter was associated with pelvic organ prolapse treatment in 16 patients (15.7%). Three-year minimum follow-up (median, 40 mo) was available for 91 patients (89.2%). No erosion or persistent pain was noted. Four patients required tape release or section. Disappearance and improvement of SUI were observed in 88.4% and 9.3% of the patients, respectively. These cure rates were similar to those obtained 1 yr after the operation (p=0.55). Frequency and urge symptoms were improved at 3 yr (p<0.005). Whereas maximum flow rates were somewhat decreased (p=0.01), the severity of obstructive symptoms and PVR volumes were not statistically different (p=0.11 and p=0.32, respectively). Incontinence severity and QoL scale scores were largely better than preoperative ones (p<0.001) and did not differ from those reported at 1 yr (p=0.15 and p=0.08, respectively). CONCLUSIONS: The TVT-O procedure is a safe and efficient treatment of female SUI, with maintenance of high cure rates after a 3 yr minimum follow-up. PMID- 17728053 TI - Editorial comment on: TVT-O for the treatment of female stress urinary incontinence: results of a prospective study after a 3-year minimum follow-up. PMID- 17728054 TI - Editorial comment on: Dorsal onlay skin graft bulbar urethroplasty: long-term follow-up. PMID- 17728055 TI - Stochastic P systems and the simulation of biochemical processes with dynamic compartments. AB - We introduce a sequential rewriting strategy for P systems based on Gillespie's stochastic simulation algorithm, and show that the resulting formalism of stochastic P systems makes it possible to simulate biochemical processes in dynamically changing, nested compartments. Stochastic P systems have been implemented using the spatially explicit programming language MGS. Implementation examples include models of the Lotka-Volterra auto-catalytic system, and the life cycle of the Semliki Forest virus. PMID- 17728056 TI - P systems applications to systems biology. PMID- 17728057 TI - Ascriptional and 'genuine' autonomy. AB - Knowing that human judgment can be fallible, we propose to distinguish the subjective ascription of a property, such as autonomy, from the genuine fact that an entity is characterised by a certain property, i.e., it is autonomous. In this paper, we take a closer look at this distinction and what it is grounded on, taking a constructivist stance that sees the scientist as an observing subject. We arrive at a notion of fortified ascription, in which knowledge and scientific study of generative mechanisms play an important role, and look at some models of autonomy in the light of this distinction. PMID- 17728058 TI - Development of cloud point extraction for simultaneous extraction and determination of gold and palladium using ICP-OES. AB - Cloud point method was applied for the simultaneous extraction and preconcentration of trace amounts of gold and palladium. The extraction of analytes was performed in the presence of 1,8-diamino-4,5-dihydroxy anthraquinone as chelating agent and Triton X-114 as a non-ionic surfactant. After phase separation, the surfactant-rich phase was diluted with concentrated HNO(3) (65%, w/w) and the analytes concentrations were determined by inductively coupled plasma-optical emission spectrometry (ICP-OES). The variables affecting the complexation and extraction conditions were optimized and under the optimum conditions (i.e. pH 6.5, 2.2 x 10(-4) mol l(-1) chelating agent, 0.15% (w/v) of Triton X-114, equilibration temperature 55 degrees C, centrifuge at 3500 rpm), quantitative extraction of Au(III) and Pd(II) from 100 ml of the aqueous solution was performed. The calibration curves were linear in the range of 0.5-1000 microg l(-1) with detection limits of 0.5 and 0.3 microg l(-1) and the enrichment factors were 8.6 and 20.2 for Au and Pd, respectively. Also the precision (%RSD) for eight replicate determinations of the analytes was better than 5%. Finally, the proposed method was successfully applied for the determination of Au and Pd in mine stones and standard reference materials (SRM). PMID- 17728059 TI - Characterization of air pollution control residues produced in a municipal solid waste incinerator in Portugal. AB - This study is mainly related with the physical and chemical characterization of a solid waste, produced in a municipal solid waste (MSW) incineration process, which is usually referred as air pollution control (APC) residue. The moisture content, loss on ignition (LOI), particle size distribution, density, porosity, specific surface area and morphology were the physical properties addressed here. At the chemical level, total elemental content (TC), total availability (TA) and the leaching behaviour with compliance tests were determined, as well as the acid neutralization capacity (ANC). The main mineralogical crystalline phases were identified, and the thermal behaviour of the APC residues is also shown. The experimental work involves several techniques such as laser diffraction spectrometry, mercury porosimetry, helium pycnometry, gas adsorption, flame atomic absorption spectrometry (FAAS), ion chromatography, scanning electron microscopy (SEM), X-ray fluorescence (XRF), X-ray diffraction (XRD) and simultaneous thermal analysis (STA). The results point out that the APC residues do not comply with regulations in force at the developed countries, and therefore the waste should be considered hazardous. Among the considered heavy metals, lead, zinc and chromium were identified as the most problematic ones, and their total elemental quantities are similar for several samples collected in an industrial plant at different times. Moreover, the high amount of soluble salts (NaCl, KCl, calcium compounds) may constitute a major problem and should be taken into account for all management strategies. The solubility in water is very high (more than 24% for a solid/liquid ratio of 10) and thus the possible utilizations of this residue are very limited, creating difficulties also in the ordinary treatments, such as in solidification/stabilization with binders. PMID- 17728060 TI - Cleaning of waste smelter slags and recovery of valuable metals by pressure oxidative leaching. AB - Huge quantities of slag, a waste solid product of pyrometallurgical operations by the metals industry are dumped continuously around the world, posing a potential environmental threat due to entrained values of base metals and sulfur. High temperature pressure oxidative acid leaching of nickel smelter slags was investigated as a process to facilitate slag cleaning and selective dissolution of base metals for economic recovery. Five key parameters, namely temperature, acid addition, oxygen overpressure, solids loading and particle size, were examined on the process performance. Base metal recoveries, acid and oxygen consumptions were accurately measured, and ferrous/ferric iron concentrations were also determined. A highly selective leaching of valuable metals with extractions of >99% for nickel and cobalt, >97% for copper, >91% for zinc and <2.2% for iron was successfully achieved for 20 wt.% acid addition and 25% solids loading at 200-300 kPa O(2) overpressure at 250 degrees C in 2h. The acid consumption was measured to be 38.5 kg H(2)SO(4)/t slag and the oxygen consumption was determined as 84 kg O(2)/t slag which is consistent with the estimated theoretical oxygen consumption. The as-produced residue containing less than 0.01% of base metals, hematite and virtually zero sulfidic sulfur seems to be suitable for safe disposal. The process seems to be able to claim economic recovery of base metals from slags and is reliable and feasible. PMID- 17728061 TI - Properties of MSW fly ash-calcium sulfoaluminate cement matrix and stabilization/solidification on heavy metals. AB - In this paper, investigations were undertaken to formulate the properties of fly ash-calcium sulfoaluminate (CSA) cement matrix by blending MSW fly ash with CSA cement. The compressive strength, pore structure, hydration phases, and leaching behavior of Zn and Pb doped MSW fly ash-CSA cement matrices were determined by XRD, MIP, DSC, FTIR, EDX, TCLP leaching test and other experiments. The results showed that the addition of MSW fly ash to form fly ash-CSA cement matrix reduced the compressive strengths of matrices and made the pore distribution of matrices coarser, compared to that of pure CSA cement matrix. However, fly ash-CSA cement matrix could effectively immobilize high concentration of heavy metal such as lead and zinc with much lesser leaching of TCLP. Besides ettringite AFt, Friedel phase was a new hydration phase formed in the matrix. The formation of these hydration phases was responsible for huge reservoir of heavy metal stabilization by chemical fixing. Therefore, it could be postulated that MSW fly ash-CSA cement matrix was a potential new constituent of S/S matrix for high concentration of heavy metals such as Zn and Pb ions. PMID- 17728062 TI - A multiple shutdown method for managing evacuation in case of major fire accidents in chemical clusters. AB - This paper may be regarded as the second part of a larger article. The basic decision model developed in the first part of the article by Reniers et al. [G.L.L. Reniers, N. Pauwels, A. Audenaert, B.J.M. Ale, K. Soudan, Management of evacuation in case of fire accidents in chemical industrial areas, J. Hazard. Mater., 147 (2007) 478-487] is extended to determine both the optimal time and the optimal mode to stop the ongoing activities in case of a major fire possibly giving rise to an escalating event. Chemical plants have multiple modes to stop their production processes, differing with respect to the resulting costs, and with respect to the required time and personnel to complete the shutdown operations. The existence of an additional and more economic (but slower) shutdown mode might encourage the decision maker to stop the production processes earlier, in a less intervening manner, whereas the availability of an additional faster (but less economic) shutdown procedure might stimulate the decision maker to stop the production processes later, in a more intervening manner. PMID- 17728063 TI - Copper recovery and cyanide oxidation by electrowinning from a spent copper cyanide electroplating electrolyte. AB - Copper-cyanide bleed streams arise from contaminated baths from industrial electroplating processes due to the buildup of impurities during continuous operation. These streams present an elevated concentration of carbonate, cyanide and copper, constituting a heavy hazard, which has to be treated for cyanide destruction and heavy metals removal, according to the local environmental laws. In the Brazilian Mint, bleed streams are treated with sodium hypochlorite, to destroy cyanide and precipitate copper hydroxide, a solid hazardous waste that has to be disposed properly in a landfill or treated for metal recovery. In this paper, a laboratory-scale electrolytic cell was developed to remove the copper from the bleed stream of the electroplating unit of the Brazilian Mint, permitting its reutilization in the plant and decreasing the amount of sludge to waste. Under favorable conditions copper recoveries around 99.9% were achieved, with an energy consumption of about 11 kWh/kg, after a 5-h electrolysis of a bath containing copper and total cyanide concentrations of 26 and 27 g/L, respectively. Additionally, a substantial reduction of the cyanide concentration was also achieved, decreasing the pollution load and final treatment costs. PMID- 17728064 TI - E2F1 is not essential for apoptosis induced by potassium deprivation in cerebellar granule neurons. AB - Cerebellar granule neurons (CGNs) undergo apoptosis when deprived of depolarizing concentration of potassium. A key regulator of cell cycle, E2F1, was believed to play a role in CGN apoptosis induced by potassium deprivation. However, here we demonstrated that although E2F1 was upregulated in wild type CGNs following potassium deprivation, CGNs that derived from E2F1 knockout mice underwent apoptosis at a similar rate as the wild type. Analysis of the apoptotic neurons revealed no difference in the activation of caspase-3 in E2F1 null and wild type CGNs. Furthermore, knockdown of E2F1 expression by RNA interference failed to attenuate the apoptosis of CGNs induced by potassium deprivation. Taken together, our results suggested that E2F1 is not essential for apoptosis induced by potassium deprivation in CGNs. PMID- 17728065 TI - Chronic pain syndromes: you can't have one without another. PMID- 17728066 TI - The diabetic gut--both aching and unfeeling? PMID- 17728067 TI - Cryptosporidium and Giardia as foodborne zoonoses. AB - Cryptosporidium and Giardia are major causes of diarrhoeal disease in humans, worldwide and are major causes of protozoan waterborne diseases. Both Cryptosporidium and Giardia have life cycles which are suited to waterborne and foodborne transmission. There are 16 'valid'Cryptosporidium species and a further 33+ genotypes described. Parasites which infect humans belong to the Giardia duodenalis "type", and at least seven G. duodenalis assemblages are recognised. Cryptosporidium parvum is the major zoonotic Cryptosporidium species, while G. duodenalis assemblages A and B have been found in humans and most mammalian orders. In depth studies to determine the role of non-human hosts in the transmission of Cryptosporidium and Giardia to humans are required. The use of harmonised methodology and standardised and validated molecular markers, together with sampling strategies that provide sufficient information about all contributors to the environmental (oo)cyst pool that cause contamination of food and water, are recommended. Standardised methods for detecting (oo)cysts in water are available, as are optimised, validated methods for detecting Cryptosporidium in soft fruit and salad vegetables. These provide valuable data on (oo)cyst occurrence, and can be used for species and subspecies typing using appropriate molecular tools. Given the zoonotic potential of these organisms, epidemiological, source and disease tracking investigations involve multidisciplinary teams. Here, the role of the veterinarian is paramount, particularly in understanding the requirement for adopting comprehensive sampling strategies for analysing both sporadic and outbreak samples from all potential non-human contributors. Comprehensive sampling strategies increase our understanding of parasite population biology and structure and this knowledge can be used to determine what level of discrimination is required between isolates. Genetic exchange is frequent in C. parvum populations, leading to recombination between alleles at different loci, the generation of a very large number of different genotypes and a high level of resolution between isolates. In contrast, genetic exchange appears rare in Cryptosporidium hominis and populations are essentially clonal with far fewer combinations of alleles at different loci, resulting in a much lower resolution between isolates with many being of the same genotype. Clearly, more markers provide more resolution and high throughput sequencing of a variety of genes, as in multilocus sequence typing, is a way forward. Sub-genotyping tools offer increased discrimination, specificity and sensitivity, which can be exploited for investigating the epidemiology of disease, the role of asymptomatic carriers and contaminated fomites and for source and disease tracking for food and water contaminated with small numbers of (oo)cysts. PMID- 17728068 TI - The CCAAT-binding factor CBF/NF-Y regulates the human acetylcholinesterase promoter activity during calcium ionophore A23187-induced cell apoptosis. AB - We previously reported that the expression of acetylcholinesterase during A23187 induced apoptosis of HeLa cells is regulated by Ca(2+) mobilization through the modulation of mRNA stability and acetylcholinesterase promoter activity. Transactivation of the human acetylcholinesterase promoter by A23187 was partially mediated by the distal CCAAT motif within the -1270 to -1248 fragment of the human acetylcholinesterase promoter, which was bound by the CCAAT binding factor (CBF/NF-Y). In the present study, we investigated the molecular mechanisms by which CBF/NF-Y regulates A23187-induced activation of the human acetylcholinesterase promoter. The results indicate that CBF/NF-Y binding to the distal CCAAT motif suppresses the promoter activity. Electrophoretic mobility shift assays (EMSAs) demonstrated that binding of CBF/NF-Y to the distal CCAAT motif decreased after A23187 treatment. Our results suggest that acetylcholinesterase promoter activation during A23187-induced HeLa cell apoptosis may result partly from the dissociation of CBF/NF-Y from the distal CCAAT motif in the acetylcholinesterase promoter, reversing this suppression. PMID- 17728069 TI - Reasons for nonresponse in a web-based survey of alcohol involvement among first year college students. AB - This study conducted a follow-up telephone survey of a probability sample of college students who did not respond to a Web survey to determine correlates of and reasons for nonresponse. A stratified random sample of 2502 full-time first year undergraduate students was invited to participate in a Web-based survey. A random sample of 221 students who did not respond to the original Web survey completed an abbreviated version of the original survey by telephone. Nonresponse did not vary by gender, but nonresponse was higher among Blacks and Hispanics compared to Whites, and Blacks compared to Asians. Nonresponders reported lower frequency of past 28 days drinking, lower levels of past-year and past 28-days heavy episodic drinking, and more time spent preparing for classes than responders. The most common reasons for nonresponse were "too busy" (45.7%), "not interested" (18.1%), and "forgot to complete survey" (18.1%). Reasons for nonresponse to Web surveys among college students are similar to reasons for nonresponse to mail and telephone surveys, and some nonresponse reasons vary as a function of alcohol involvement. PMID- 17728070 TI - What of apoptosis is important: the decay process or the causative origin? AB - Apoptosis is defined as the process of ''programmed cell death'' (PCD), during which many cells simultaneously die from within along a very orderly pattern. PCD is as intrinsic for cells as mitosis and is involved in both degenerative and developmental processes of organs and organisms. The pattern of apoptotic cell decay is caused by the total cellular content. Since all body cells possess the same genome, they are similar in many aspects and, therefore, the major processes are nearly identical in all cell types. The same destructive processes also occur continuously in healthy living cells, but then the capacity of repair mechanisms is sufficient to effect cellular integrity. Decay processes become visible, as soon as repair can no more be sufficient. PCD starts as soon as produced energy is permanently insufficient to repress decay. Decreased energy production may arise due to (i) turning off the pivotal tricarbonic acid cycle, (ii) turning off oxidative phosphorylation, (iii) damage of mitochondria, and (iv) inhibition of mitochondrial biogenesis regarding both the mitochondrial and the nuclear part. The consequence of this kind of decreased energy production will be a massive, inefficient fermentative energy production with enormous amounts of lactic acid. Increasing acidity and falling pH will slow down enzymatic activities and thus also intracellular processes. As soon as energy for repair has become insufficient, cellular decay becomes irreversible and the cell will die. Thus, the mitochondrial apoptotic pathway is suggested to arise due to low mitochondrial energy production. For optimal functioning cells need adequate internal conditions and cellular morphology. Cellular morphology depends on (i) the intracellular turgor, (ii) the intracellular cytoskeleton, and (iii) close intercellular contact with neighbour cells. Lack of energy implies decrease of turgor and, consequently, a strong decline of conditions needed for adequate functioning of the cell. Thus, if this lack of energy cannot be repaired in time, it will contribute to cellular decay. Various cellular components or systems that are not directly linked to mitochondria, may be functionally inhibited or damaged and thus contribute to apoptosis. These components or systems that probably constitute the non-mitochondrial pathway are (i) the cellular uptake systems for energy-rich substrates, (ii) extra-mitochondrial enzymes that are involved in non mitochondrial processes of oxidative energy production, (iii) cytoplasmatic, non mitochondrial protein synthesis, (iv) the system that regulates osmotic conditions and turgor, and (v) the synthesis and repair of the cytoskeleton. After this careful reflection I am convinced that apoptosis is merely the complex machinery of cellular decay after energy generation has irreversibly stopped. Therefore, apoptosis research for health care should be focussed on processes that hinder energy production. For therapeutic aims research should be focussed on metabolic aspects of energy production and on mitochondrial processes. PMID- 17728072 TI - Fasciitis ossificans of the breast. AB - We report a rare case of fasciitis ossificans of the breast. A nodule of the breast was incidentally found in a 77-year-old woman without a history of trauma. The painless lesion was located 3 cm from the nipple in the lower outer quadrant of the left breast. Excisional biopsy was performed, and there has been no evidence of recurrence or metastasis for 2 years. The 1.8 cm diameter nodule was well demarcated from the adjacent tissue and located 2.5 cm beneath the skin. Histologically, the lesion was composed of uniform woven bone trabeculae with rimming of osteoblasts and fibrous stroma. At the periphery, spindle cells actively proliferated in edematous stroma, demonstrating uniform nuclei without increased chromatin, pleomorphism, or evident nucleoli. We counted 2 mitotic figures per 10 high-power fields, but no atypical forms were observed. Spindle cells were immunoreactive for vimentin and alpha-smooth muscle actin, suggesting myofibroblastic differentiation. Fasciitis ossificans is histologically identical to myositis ossificans, but tends to present no zonation phenomenon. We considered this lesion as fasciitis ossificans since it was situated at the superficial layer of the mammary gland. To avoid an unnecessarily aggressive treatment, fasciitis ossificans, a benign bone-forming nodule, needs to be considered in the differential diagnosis of breast hard tumor. PMID- 17728071 TI - The biochemical origin of pain: the origin of all pain is inflammation and the inflammatory response. Part 2 of 3 - inflammatory profile of pain syndromes. AB - Every pain syndrome has an inflammatory profile consisting of the inflammatory mediators that are present in the pain syndrome. The inflammatory profile may have variations from one person to another and may have variations in the same person at different times. The key to treatment of Pain Syndromes is an understanding of their inflammatory profile. Pain syndromes may be treated medically or surgically. The goal should be inhibition or suppression of production of the inflammatory mediators and inhibition, suppression or modulation of neuronal afferent and efferent (motor) transmission. A successful outcome is one that results in less inflammation and thus less pain. We hereby briefly describe the inflammatory profile for several pain syndromes including arthritis, back pain, neck pain, fibromyalgia, interstitial cystitis, migraine, neuropathic pain, complex regional pain syndrome/reflex sympathetic dystrophy (CRPS/RSD), bursitis, shoulder pain and vulvodynia. These profiles are derived from basic science and clinical research performed in the past by numerous investigators and serve as a foundation to be built upon by other researchers and will be updated in the future by new technologies such as magnetic resonance spectroscopy. Our unifying theory or law of pain states: the origin of all pain is inflammation and the inflammatory response. The biochemical mediators of inflammation include cytokines, neuropeptides, growth factors and neurotransmitters. Irrespective of the type of pain whether it is acute or chronic pain, peripheral or central pain, nociceptive or neuropathic pain, the underlying origin is inflammation and the inflammatory response. Activation of pain receptors, transmission and modulation of pain signals, neuro plasticity and central sensitization are all one continuum of inflammation and the inflammatory response. Irrespective of the characteristic of the pain, whether it is sharp, dull, aching, burning, stabbing, numbing or tingling, all pain arise from inflammation and the inflammatory response. We are proposing a re-classification and treatment of pain syndromes based upon their inflammatory profile. PMID- 17728073 TI - Heterotopic ossification: review of histologic findings and tissue distribution in a 10-year experience. AB - Heterotopic ossification (HO) within tissues involved by a pathologic process is a well-recognized phenomenon. It is most frequently observed in atherosclerotic plaques, in soft tissue around joints, and in the central nervous system. Less frequently, carcinomas and some benign neoplasms will undergo heterotopic ossification. We performed a retrospective review of our experience with HO over a 10-year period to determine the frequency and tissue site distribution of heterotopic ossification. A computerized review of surgical pathology records of approximately 126,000 reports revealed 85 cases in which heterotopic ossification, ectopic bone or metaplastic bone was specifically mentioned in the surgical pathology diagnosis. Twenty-two cases were neoplasms of non-osseous tissues, and 63 cases were non-neoplastic lesions. Immunohistochemical staining for bone morphogenic proteins (BMP) 1, 4, and 6 was performed. Fourteen cases showed staining for BMP-1, 22 cases showed staining for BMP-4, and five cases showed weak staining for BMP-6. HO is a relatively infrequent finding and is more commonly seen in degenerative and reparative conditions than in neoplasms. PMID- 17728074 TI - Stimulus comparison in perceptual learning: roles of sensory preconditioning and latent inhibition. AB - Rats were given exposure to a compound flavour (AX) and to one element of that compound (X). Two drinking tubes were made available to the rat on each exposure trial. For group concurrent (CNC) one tube contained AX and the other X. For groups alternating (ALT) and blocked (BLK), however, both tubes contained the same flavour (AX or X). Group ALT received AX and X on alternate trials; group BLK received AX in the first block of trials and X on the second, or vice versa. After an aversion had been established to X the groups were tested with AX. It was found that group ALT showed less generalization from X to AX than did group BLK. This difference was not accompanied by a parallel difference in the level of conditioning to X. However, group CNC showed both stronger conditioning to X and greater generalization from X to AX than groups ALT and BLK. Implications for the role of stimulus comparison in the perceptual learning effect are discussed. PMID- 17728075 TI - A study on the TNF-alpha system in Caucasian Spanish patients with alcoholic liver disease. AB - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is thought to be a critical driving force of inflammatory damage in alcoholic liver disease (ALD). We aimed to establish whether there is a correlation between plasma levels of the soluble TNF-alpha receptors 1 and 2 (sTNFR1 and sTNFR2) and the severity of liver damage in patients with ALD. We also aimed to elucidate whether functionally active polymorphisms in the promoter region of the TNF-alpha gene modulate the development of ALD. DESIGN: We studied 614 Spaniards. Of these, 278 were alcoholics (103 without liver histologic abnormalities, 89 with non-cirrhotic liver disease and 86 with cirrhosis) and 336 were non-alcoholics (115 healthy controls, 114 with non-alcoholic non-cirrhotic liver disease and 107 with cirrhosis unrelated to alcohol). Plasma levels of sTNFR1 and sTNFR2 were determined by ELISA and results were expressed in ng/mL and subsequently converted in log(10). TNF-alpha gene promoter region polymorphisms at the positions -238, -308 and -863 were assessed by restriction fragment length polymorphisms (RFLPs) on white cell DNA. Differences in plasma sTNFR1 and sTNFR2 levels between groups were compared with the one-way and two-factor analysis of variance test, and Student's t-test. Genotype distribution and allele frequencies in the different groups were compared using the chi(2) test or Fisher's exact test. RESULTS: sTNFR1 and sTNFR2 plasma levels were significantly higher in patients with cirrhosis than in those with non-cirrhotic liver disease (p<0.001) and individuals without liver disease (p<0.001), both in the alcoholic and the non-alcoholic group. Among cirrhotics, sTNFR1 and sTNFR2 levels had a significant positive correlation with the severity of the liver disease, graded with the Child-Pugh's score (p=0.003 and p<0.001, respectively). TNF-alpha genotype distribution and allele frequencies of the three loci assessed were similar in the groups studied, hence no particular genotype or haplotype could be linked to ALD. CONCLUSIONS: The TNF-alpha system is activated in patients with cirrhosis of the liver irrespective of aetiology. TNF-alpha polymorphisms at positions -238, 308 and -863 are not linked to ALD. PMID- 17728076 TI - Loss of the rpl32 gene from the chloroplast genome and subsequent acquisition of a preexisting transit peptide within the nuclear gene in Populus. AB - Gene transfer events from organelle genomes (mitochondria and chloroplasts in plants) to the nuclear genome are important processes in the evolution of the eukaryotic cell. It is highly likely that the gene transfer event is still an ongoing process in higher plant mitochondria and chloroplasts. The number and order of genes encoded in the chloroplast genome of higher plants are highly conserved. Recently, several exceptional cases of gene loss from the chloroplast genome have been discovered as the number of complete chloroplast genome sequences has increased. The Populus chloroplast genome has lost the rpl32 gene, while the corresponding the chloroplast rpl32 (cp rpl32) gene has been identified in the nuclear genome. Nuclear genes transferred from the chloroplast genome need to gain a sequence that encodes a transit peptide. Here, we revealed that the nuclear cp rpl32 gene has acquired the exon sequence, which is highly homologous to a transit peptide derived from the chloroplast Cu-Zn superoxide dismutase (cp sod-1) gene. The cp rpl32 gene has acquired the sequence that encodes not only for the transit peptide, but also for the conserved N-terminal portion of the mature SOD protein from the cp sod-1 gene, suggesting the occurrence of DNA sequence duplication. Unlike cp SOD-1, cp RPL32 did not show biased localization in the chloroplasts. This difference may be caused by mutations accumulated in the sequence of the SOD domain on the cp rpl32 gene. We provide new insight into the fate of the inherent sequence derived from a transit peptide. PMID- 17728077 TI - Annual dynamics of bacterioplankton assemblages in the Gulf of Trieste (Northern Adriatic Sea). AB - Bacterioplankton community diversity was investigated monthly in coastal waters of the Gulf of Trieste (NE Adriatic Sea) throughout 2003. Superficial bacterial assemblages of two differently freshwater influenced stations were studied using PCR-DGGE fingerprinting techniques. Bacterial genetic diversity of the sampled area, as estimates of the number of DGGE bands was high (36-64) compared to that reported in other studies employing this fingerprint technique. The similarity index (Sorensen Index) between assemblages showed a defined operational taxonomic units (OTUs) succession pattern in the more typically marine station with stable winter communities and quickly changing summer ones. On the contrary in the station affected by riverine inputs no clear pattern was detected. In both sites, according to cluster analyses performed on the DGGE banding pattern, three seasonal assemblages were identified: winter-spring, summer and fall. Sequence analysis of fifty-six among the brightest gel bands led to the observation of bacteria affiliated to Gram positive, Cyanobacteria, Cytophaga-Flavobacteria Bacteroides (CFB) lineages and the alpha-, gamma- and delta- subdivisions of the Proteobacteria. Gamma-Proteobacteria constituted the main fraction (60%) of sequences in the more typically marine station, whereas the river-influenced station was characterised by more heterogeneous assemblages (39% alpha Proteobacteria, 32% Flavobacteria). PMID- 17728078 TI - Evolutionary origin of sex-related genes in the mouse brain. AB - With the aim of elucidating the evolutionary process of sexual dimorphism in the brain at the molecular level, we conducted genomic comparisons of a set of genes expressed in a sexually different manner in the mouse brain with all genes from other species of eukaryotes. First, seventeen protein-coding genes whose levels of mRNA expression in the brain differed between male and female mice have been known according to the currently available microarray data, and we designated these genes operationally as "sex-related genes in the mouse brain". Next, we estimated the time when these sex-related genes in the mouse brain emerged in the evolutionary process of eukaryotes by examining the presence or absence of the orthologues in the 26 eukaryotic species whose genome sequences are available. As a result, we found that the ten sex-related genes in the mouse brain emerged after the divergence of urochordates and mammals whereas the other seven sex related genes in the mouse brain emerged before the divergence of urochordates and mammals. In particular, five sex-related genes out of the ten genes in the mouse brain emerged just before the appearance of bony fish which have phenotypic sexual dimorphism in the brain. Interestingly, three of these five sex-related genes that emerged during this period were classified into the "protein binding" function category. Moreover, all of these three genes were expected to have the functions that are related to cell-cell communications in the brain according to the gene expression patterns and/or functional information of these genes. These findings suggest that the orthologues of the sex-related genes in the mouse brain that emerged just before the divergence of bony fish might have essential roles in the evolution of the sexual dimorphism in the brain forming protein-protein interactions. PMID- 17728079 TI - Analysis of invariant sequences in 266 complete genomes. AB - To date, the complete genome sequences of more than 250 organisms have been determined. This information can now be used to determine whether there exist any invariant sequences that are conserved among all organisms, from bacteria to plants, animals, and humans. The existence of invariant sequences would strongly suggest that these sequences have been inherited unchanged from the last common ancestor of all life, and that they have essential functions. We have developed a new software program to identify invariant sequences conserved among the currently sequenced genomes and applied this analysis to the complete genome sequences of 266 organisms. We have identified 3 invariant DNA sequences longer than or equal to 11 bp and 6 invariant amino acid sequences longer than or equal to 6 aa. The longest invariant DNA sequence, AAGTCGTACAAGGT (15 bp), was found in the 16S/18S rRNA gene. Two 8 aa sequences, GHVDHGKT in IF2 and EF-Tu and DTPGHVDF in EF-G, were the longest invariant amino acid sequences detected. These sequences could be essential elements from the genome of the last common ancestor and may have remained unchanged throughout evolution. PMID- 17728080 TI - Detection of foot-and-mouth disease virus by nucleic acid sequence-based amplification (NASBA). AB - A study was conducted to evaluate the performance of a nucleic acid sequence based amplification (NASBA) assay for the detection of foot-and-mouth disease virus (FMDV). Two detection methods: NASBA-electrochemiluminescence (NASBA-ECL) and a newly developed NASBA-enzyme-linked oligonucleotide capture (NASBA-EOC) were evaluated. The diagnostic sensitivity of these assays was compared with other laboratory-based methods using 200 clinical samples collected from different regions of the world. Assay specificity was also assessed using samples (n=43) of other viruses that cause vesicular disease in livestock and genetic relatives of FMDV. Concordant results were generated for 174/200 (87.0%) of suspect FMD samples between NASBA-ECL and real-time RT-PCR. In comparison with the virus isolation (VI) data, the sensitivity of the NASBA-ECL assay was 92.9%, which was almost identical to that of the real-time RT-PCR (92.4%) for the same set of samples. There was broad agreement between the results of the NASBA-ECL and the simpler NASBA-EOC detection method for 97.1% of samples. In conclusion, this study provides further data to support the use of NASBA as a rapid and sensitive diagnostic method for the detection and surveillance of FMDV. PMID- 17728081 TI - Adverse neurodevelopmental outcome of infants exposed to opiate in-utero. AB - In-utero drug exposure is associated with increased risks of perinatal morbidity and mortality, however longer term neurodevelopmental outcome of survivors is poorly described. AIMS: The aims of this paper are: (1) to review the published literature which examines neurodevelopmental outcome in infants with Neonatal Abstinence Syndrome (NAS) and (2) to report developmental follow-up data from a case-control study of babies exposed to opiate in-utero. METHODS: This study was conducted at Royal Prince Alfred Hospital in Sydney, NSW, through the multidisciplinary NAS service. Literature was reviewed after searching MEDLINE for relevant studies. Our own case-control study was conducted to examine neurodevelopmental outcome. A number of standardized neuropsychological tools were employed to assess these infants. RESULTS: Results from previously published studies on outcome of infants with NAS were not reassuring as to reported 'normal development'. In our own case-control study, opiate-exposed infants were significantly more likely to have neurodevelopmental impairment compared to healthy control infants, when assessed at 18 months and 3 years of age. CONCLUSIONS: Infants exposed to opiates in-utero are at increased risk of neurodevelopmental problems throughout early childhood. PMID- 17728082 TI - Assessment of oil polarity: comparison of evaluation methods. AB - In multiple emulsion systems, oily or aqueous transfers may occur between the dispersed droplets through the continuous phase. These transfers are controlled by both the surfactant system (micellar transport), and the partial solubility of one phase in another (molecular transport). The latter could be anticipated from the knowledge of oil polarity, if this information could easily be obtained. In this work, the relative polarity of eight oils used for various purposes has been evaluated from the comparison of their dielectric requirement for solubilization, their interfacial tension and chromatographic analysis. The results showed the complementarities of HPLC analysis and interfacial tension measurements and their superiority over the solubilization method for classifying oils as a function of their polarity. PMID- 17728083 TI - Use of a passive equilibration methodology to encapsulate cisplatin into preformed thermosensitive liposomes. AB - A conventional, cholesterol-containing liposome formulation of cisplatin has demonstrated insignificant activity in clinical trials, due in part, to insufficient release of encapsulated content following localization within solid tumors. For this reason, the development of a triggered release liposome formulation is desirable. In this report, cisplatin was encapsulated into lysolipid-containing thermosensitive liposomes (LTSL) using a novel technique, which relies on the equilibration of cisplatin across the liposomal membrane at temperatures above the gel-to-liquid crystalline phase transition temperature (TC) of the bulk phospholipid. Mild heating and drug loading into LTSL did not induce morphological changes of the liposomes. In vitro data demonstrated that >95% of encapsulated cisplatin was released from LTSL within 5 min following mild heating at 42 degrees C, while <5% was released at 37 degrees C. Under similar conditions, lysolipid-free thermosensitive liposomes exhibited 70% release of cisplatin at 42 degrees C, and cholesterol-containing liposomes exhibited negligible drug release at 42 degrees C. The pharmacokinetic profiles of LTSL- and TSL-cisplatin indicated that these formulations were rapidly eliminated from circulation (terminal t(1/2) of 1.09 and 2.83 h, respectively). The therapeutic utility of LTSL-cisplatin formulation will be based on strategies where hyperthermia is applied prior to the administration of the liposomal drug-a strategy similar to that used in the clinical assessment of LTSL-doxorubicin formulation. PMID- 17728084 TI - Beyond the myth of expensive clinical study: assessment of traditional medicines. AB - Clinical studies with human subjects represent the only assessment of effectiveness and safety that can translate into medical practice, and national or local health policy. There are several reasons why traditional medicines (in fact medicinal plants and other alternative or complementary medicines) should be subjected to more clinical research with patient observation and follow-up: firstly, this would help to select products of interest for further investigations in ethnopharmacology; secondly, it could translate into immediate recommendations for the population using the assessed local treatments. Contrary to a commonly held myth, clinical studies can be conducted at relatively low cost, if one works with local/regional research institutes and with doctoral students, focusing on meaningful clinical measures rather than sophisticated laboratory analyses. This paper describes special designs of clinical studies, appropriate for traditional medicines and tested in the field, including: the retrospective treatment-outcome population survey, the prognosis- outcome method (with modern physicians observing progress of patients treated by a traditional healer), the dose-escalating prospective study (detecting a dose-response phenomenon in humans). It is suggested that this approach offers the best cost effective course of action for obtaining maximal benefits from traditional medicines, especially those used for treating endemic diseases. PMID- 17728085 TI - In vitro and in vivo evaluation of the antitrypanosomal activity of fractions of Holarrhena africana. AB - The aqueous extract of young leaves of Holarrhena africana, a plant used in the Nigerian traditional medicine, exhibited good activity against Trypanosoma brucei spp. The extract was fractionated and eight fractions were obtained. One fraction designated as HaF(5) showed in vitro activity against Trypanosoma brucei rhodesiense with an IC(50) value of 0.785 microg/mg and no overt cytotoxicity against L-6 cells. Fraction HaF(5) was tested in vivo at two doses and found to exhibit in vivo efficacy in Trypanosoma brucei brucei infected mice leading to a complete disappearance of parasitaemia followed by a relapse. PMID- 17728086 TI - Rupture of the spleen or splenic vessels (splenic emergency syndrome) in late pregnancy: a report of two autopsy cases. AB - Emergencies of splenic origin in pregnancy involving rupture of the splenic artery or hemorrhage are rare events that can present suddenly and unexpectedly. We report two cases of young women, both in the third trimester of gestation, who suffered sudden malaise while at home and were admitted to the ER. On arrival, both were in severe hemorrhagic shock due to gross hemoperitoneum and they died in the operating theatre during emergency surgery. To better clarify the causes and sequence of these mortalities, forensic autopsy was requested in each case. In the first (a 26-year-old primigravida in the 40th week of pregnancy), cadaveric section demonstrated the rupture of an aneurysm of the splenic artery. In the second (a 28-year-old multipara in the 33rd week of pregnancy), the clinical and anatomopathological data suggested splenic hemorrhage. In both cases histology showed a fibrodysplasia of the arterial wall involving the splenic artery in one case and the hilar branches in the other. In agreement with the data in literature, in such cases particular importance must be attributed to examination of the arterial wall. In pregnancy a synergic effect between hemodynamic and endocrine factors can cause degeneration of the arteries resulting in dramatic hemorrhage. From the forensic pathologist's viewpoint, these cases underline the importance of histopathological study of the splenic artery in the interpretation of the pathogenesis of splenic vessel rupture or hemorrhage. PMID- 17728087 TI - Analysis of rosin and modified rosin esters in adhesives by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). AB - The optimum method for analyzing glyceryl rosinate by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was studied. The performances of dithranol, anthracene, and 2,5-dihydroxybenzoic acid, pyrene, trans,trans-1,4-diphenyl-1,3-butadiene, 9-nitroanthracene, indole-3 acrylic acid and retinoic acid as a matrix agent, and those of sodium trifluoroacetate (NaTFA) and silver trifluoroacetate (AgTFA) as a cationization agent were measured. Dithranol showed higher signal to noise ratio and lower base line, and AgTFA showed better performance than NaTFA. In this study, however, NaTFA was chosen since the ester peaks with high signal to noise ratios were observed, and the spectra of sodium-cationized molecules are simpler than those of silver-cationized molecules. Rosin esters and modified rosin esters in 22 rubber-based pressure sensitive adhesives and a paper-cement were analyzed. Glyceryl rosinate, glyceryl disproportionated rosinate, pentaerythrityl rosinate and pentaerythrityl hydrogenated rosinate were easily detected despite the fact that rubber-based adhesives are complex mixtures of elastomers, tackifiers, antioxidants and other additives. The detection limit of this method was studied and 2% of glyceryl rosinate in a rubber-based pressure sensitive adhesive was detected. It has been proved that MALDI-TOF-MS is a useful analytical method to analyze rosin and modified rosin esters in adhesives. PMID- 17728088 TI - The neonatal progeroid syndrome (Wiedemann-Rautenstrauch): a model for the study of human aging? AB - The Wiedemann-Rautenstrauch syndrome (WRS) characterises a premature aging syndrome in which several features of human aging are apparent at birth therefore allowing their grouping as a neonatal progeroid condition. This differentiates WRS from other progeroid entities such as Hutchinson-Gilford progeria syndrome (HGPS) in which characteristics of premature aging become apparent some time after birth. The etiology of WRS remains unknown. Some studies have observed an autosomal recessive mode of inheritance. Several studies analysing telomere length and lamin A gene have not revealed any alterations. However, mutations in LMNA have been reported in several other atypical progeroid syndromes. Based on these observations, several hypothesis could be withdrawn concerning the etiology of WRS. The study of genes associated with lamin A metabolism, such as Zmpste24, and the metabolic pathways associated with insulin, such as protein kinase B or AKT, are of particular interest. We believe that WRS characteristics indicate that discovery of the gene and the metabolic pathway associated with this syndrome will most likely lead to new knowledge about the physiopathology of human aging. PMID- 17728089 TI - Radiologists' knowledge and perceptions of the impact of contrast-induced nephropathy and its risk factors when performing computed tomography examinations: a survey of European radiologists. AB - BACKGROUND: The past decade has seen a proliferation in the number of CT procedures. As increasing numbers of elderly patients with multiple comorbidities undergo contrast media (CM)-enhanced procedures, more patients are at risk for contrast-induced nephropathy (CIN). OBJECTIVES: To understand whether radiologists are sufficiently aware of the incidence, impact and risk factors of CIN, and whether they are taking sufficient measures to prevent CIN among patients undergoing CT. MATERIALS AND METHODS: A telephone or online survey was conducted in 2005 with 509 radiologists from 10 European countries. Participants had a minimum of 3 years' experience and performed at least 50 CT scans per week. RESULTS: Most (88%) radiologists believed that CIN is an important issue. While 45% identify that a patient is experiencing CIN when the serum creatinine level increases >25% (0.5mg/dL) from baseline within 48h, the remainder used criteria that might lead to significant under-diagnosis. Most (72%) radiologists believed that CIN is associated with increased morbidity; 56% did not believe that it is associated with increased mortality. Most respondents agreed that pre-existing renal impairment (97%), dehydration (90%) and diabetes (89%) were risk factors for CIN; however, 26%, 30% and 46%, respectively, did not identify advanced age, CM dose or congestive cardiac failure as risk factors. Only 7% of radiologists thought they were always made aware of CIN associated with their cases and 28% never consulted a nephrologist to discuss patients at risk of CIN or who had developed CIN. CONCLUSION: There is highly variable awareness of the definition, impact and risk factors for CIN among European radiologists. Data regarding the importance of CIN in CT are limited. Improved efforts are required to better educate radiologists and referring physicians and to institute appropriate protocols to identify at-risk patients and prevent CIN. PMID- 17728090 TI - 1H magnetic resonance spectroscopy of the normal testis: preliminary findings. AB - PURPOSE: The purpose of this study was to determine the pre- and postpubertal 1H magnetic resonance spectroscopic characteristics of the normal testis to establish baseline values for further clinical studies. MATERIALS AND METHODS: The subjects consisted of male volunteers, of whom 19 were prepubertal with ages between 7 and 13 years and 24 were postpubertal with ages between 19 and 39 years. Their testes were evaluated at 1.5 T with magnetic resonance spectroscopy; in addition, testis volumes were measured. Major metabolite peaks were identified and their ratios were calculated. Metabolite differences of testis between pre- and postpubertal age were analyzed. RESULTS: Major constituents of spectra were 3.21 ppm choline and 0.9-1.3 ppm lipid peaks. At the echo time (TE) spectrum of 31 ms, choline/lipid ratios ranged from 0.35 to 8.30 (mean=1.87) in postpubertal males and from 0.06 to 5.45 (mean=0.88) in prepubertal males (P<.013). At the TE spectrum of 136 ms, choline/lipid ratios ranged from 0.66 to 15.42 (mean=4.09) in postpubertal males and from 0.05 to 4.91 (mean=0.9) in prepubertal males (P<.016). CONCLUSIONS: Choline/lipid ratio was higher in the postpubertal period. The existence of higher choline peak in that age group should be due to the initiation of spermatogenesis. The decrease in the lipid peak may represent the effect of testosterone on testicular tissue or may be due to histochemical changes initiated by puberty. The significant decrease in choline/lipid ratio noted after puberty could represent the presence of spermatogenesis. This hypothesis should be evaluated by further studies on postpubertal subjects with impaired spermatogenesis. PMID- 17728091 TI - A two-compartment gel phantom for optimization and quality assurance in clinical BOLD fMRI. AB - Clinical applications of blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) depend heavily on robust paradigms, imaging methods and analysis procedures. In this work, as a means to optimize and perform quality assurance of the entire imaging and analysis chain, a phantom that provides a well known and reproducible signal change similar to a block type fMRI experiment is presented. It consists of two gel compartments with slightly different T2 that dynamically enter and leave the imaged volume. The homogeneous gel in combination with a cylindrical geometry results in a well-defined T*2 difference causing a signal difference between the two compartments in T*2-weighted MR images. From time series data obtained with the phantom, maps of percent signal change (PSC) and t-values are calculated. As an example of image parameter optimisation, the phantom is demonstrated to be useful for accurate determination of the influence of echo time (TE) on BOLD fMRI results, taking the t-value as a measure of sensitivity. In addition, the phantom is proposed as a tool for quality assurance (QA) since reproducible time series and t-maps are obtained in a series of independent repeat experiments. The phantom is relatively simple to build and can therefore be used by any clinical fMRI center. PMID- 17728092 TI - Circulating cathepsin K and cystatin C in patients with cancer related bone disease: clinical and therapeutic implications. AB - The clinical significance of serum cathepsin K and cystatin C was assessed in patients with breast cancer (BCa) or prostate cancer (PCa) with confined disease (M0) or bone metastasis (BM). Cathepsin K and cystatin C circulating levels were determined by ELISAs in 63 cancer patients, in 35 patients with nonmalignant diseases and in 42 healthy blood donors (control group). In BCa patients, cathepsin K serum levels were significantly lower than in sex matched control group (HS; p=0.0008) or in patients with primary osteoporosis (OP; p=0.0009). On the contrary, cystatin C levels were significantly higher in BCa patients than in HS (p=0.0001) or OP (p=0.017). In PCa patients, cathepsin K concentrations did not significantly differ from those measured in sex matched HS or in patients with benign prostatic hyperplasia (BPH). Conversely, cystatin C was more elevated in cancer patients than in controls (p=0.0001) or BPH patients (p=0.0078). Furthermore, in PCa patients, a positive correlation was observed between cystatin C and cathepsin K (r(S)=0.34; p=0.047). No further relationship was highlighted between these molecules and the clinicobiological parameters of BCa or PCa progression including the number of bone lesions. Moreover, ROC curve analysis showed a poor diagnostic performance of cathepsin K and cystatin C in the detection of BM patients. Interestingly, the administration of zoledronic acid (ZA), a bisphosphonate derivative endowed with a potent antiosteoclastic activity, induced in BM patients a marked increase of cathepsin K and cystatin C serum levels compared to baseline values. However, this phenomenon was statistically significant only in the PCa group. In conclusion Cystatin C and cathepsin K may be regarded as possible markers to monitor the therapeutic response to bisphosphonate treatments. Nevertheless, their clinical value as specific gauges of skeletal metastasis remains questionable. PMID- 17728093 TI - Changes in antioxidant defense systems induced by thiram in V79 Chinese hamster fibroblasts. AB - The role of antioxidant defence systems in protection against oxidative damage of lipids and proteins induced by fungicide thiram during in vitro exposure was investigated in cultured Chinese hamster V79 cells with normal, depleted, and elevated glutathione (GSH) levels. We analyzed the catalytic activities of superoxide dismutases (SOD1 and SOD2), Se-dependent and Se-independent glutathione peroxidases (GSH-Px), glutathione reductase (GR), and catalase (CAT), as well as total glutathione/glutathione disulfide ratio (GSH(total)/GSSG). Thiram treatment resulted in an increase in activities of SOD1, Se-dependent GSH Px, and GR at the highest tested dose (150 microM). On the contrary, inhibition of CAT and Se-independent GSH-Px activities, and no significant changes in the level of SOD2 activity was observed at any tested doses (100-150 microM). GSH(total)/GSSG ratio in the 100 microM thiram treated cells was not significantly changed comparing to the control, despite significant decrease of GSH total (50%). In 150 microM thiram treated cells the ratio falls to 43% of control value. Pretreatment with l-buthionine sulfoximine (L-BSO), an inhibitor of GSH synthesis, significantly enhanced decrease in CAT and Se-independent GSH Px activities, as well as GSH(total)/GSSG ratio, and reduced Se-dependent GSH-Px activity, following exposure to thiram. Simultaneously, L-BSO pretreatment enhanced increase in SOD1 activity, and had no effect on SOD2, following thiram exposure. Pretreatment with N-acetyl cysteine (NAC), a GSH precursor, prevented enzymatic changes in CAT, Se-dependent GSH-Px, GR, SOD1 activities, and significantly decreased SOD2 activity following exposure to thiram. GSH(total)/GSSG ratio was restored to the control value. This study suggests that following the changes in antioxidant defense systems thiram can act through the production of free radicals. PMID- 17728094 TI - Aconitine alters connexin43 phosphorylation status and [Ca2+] oscillation patterns in cultured ventricular myocytes of neonatal rats. AB - Aconitine, a highly poisonous type of alkaloid, has a widespread effect in stimulating the membranes of cardiomyocyte. However, other effects of aconitine on cardiomyocyte are unknown. In this study, we investigated whether aconitine also affects the phosphorylation status of connexin43 (Cx43) and intracellular [Ca(2+)] oscillation patterns in cultured ventricular myocytes of neonatal rats. As determined by Western blot analysis, a decreased percentage (47.68+/-2.29%) of phosphorylated Cx43 (P-Cx43) and a concomitant increased percentage (52.32+/ 2.29%) of nonphosphorylated Cx43 (NP-Cx43) were found in aconitine-treated cultures, compared to the controls (82.77+/-2.04% for P-Cx43 and 17.23+/-2.04% for NP-Cx43). Quantitative immunofluorescent microscopy revealed similar changes in phosphorylation status occurring in Cx43 containing gap junctions in the cultures under the same treatment conditions. Real-time laser scanning microscopy indicated that intracellular [Ca(2+)] oscillations were relatively stable in control cultures, with occasional calcium sparks; after being treated with aconitine, high frequency [Ca(2+)] oscillations emerged, whereas typical calcium sparks disappeared. Furthermore, Western blot analysis revealed that, after aconitine treatment, the amount of phosphorylated PKCalpha decreased significantly. These observations suggest that aconitine not only induces dephosphorylation of Cx43 and PKCalpha, but also alters intracellular [Ca(2+)] oscillation patterns in cultured cardiomyocytes. PMID- 17728095 TI - Genotoxic, mutagenic and cytotoxic effects of the commercial dye CI Disperse Blue 291 in the human hepatic cell line HepG2. AB - Textile dyes are discarded into the aquatic ecosystem via industrial effluents and potentially expose humans and local biota to adverse effects. The commercial dye CI Disperse Blue 291 which contains the aminoazobenzene 2-[(2-bromo-4,6 dinitrophenyl)azo]-5(diethylamino)-4-methoxyacetanilide (CAS registry no. 56548 64-2), was tested for genotoxicity and cytotoxicity in the human hepatoma cell line HepG2, using the comet assay, micronucleus (MN) test and a cell viability test. Five different concentrations of the test compound were examined: 200 microg/ml, 400 microg/ml, 600 microg/ml, 800 microg/ml and 1000 microg/ml. An increase in comet tail length and in the frequency of MN was detected with exposure of cells to concentrations of the commercial dye from 400 microg/ml. Furthermore, the dye was found to decrease cell viability. The results of this study demonstrate for the first time the genotoxic and mutagenic effects of the dye CI Disperse Blue 291 in mammalian cells, thus stressing the need to develop non-mutagenic dyes and to invest in improving the treatment of effluents. These measures will help to prevent harmful effects that these compounds can have on humans and aquatic organisms that come in contact with them. PMID- 17728096 TI - Commentary on "Cogniform disorder and cogniform condition: proposed diagnoses for excessive cognitive symptoms" by Dean C. Delis and Spencer R. Wetter. PMID- 17728097 TI - Social phobia with sudden onset--post-panic social phobia? AB - Overlap between social phobia (SP) and panic disorder (PD) has been observed in epidemiological, family, and challenge studies. One possible explanation is that some cases of SP develop as a consequence of a panic attack in a social situation. By definition, these cases of SP have sudden onset. It is hypothesized that patients with SP with sudden onset are more similar to patients with comorbid SP and PD than to patients with SP without sudden onset regarding age of onset, extraversion, and prevalence of anxiety symptoms. One hundred and eighty two patients with a lifetime diagnosis of PD and/or SP were recruited as part of an etiological study. Patients with SP with sudden onset did, as hypothesized, differ from patients with SP without sudden onset with regard to age of onset and extraversion, but not with regard to symptoms. They did not differ markedly from patients with comorbid SP and PD. The concept of post-panic SP is discussed. PMID- 17728098 TI - A cross-species comparison of X-chromosome inactivation in Eutheria. AB - Mammalian X-chromosome inactivation achieves dosage compensation between the sexes by the silencing of one X chromosome in females. In Eutheria, X inactivation is initiated by the large noncoding RNA Xist; however, it is unknown how this RNA results in silencing of the chromosome or why, at least in humans, many genes escape silencing in somatic cells. We have sequenced the coast mole Xist gene and compared the Xist RNA sequence among seven eutherians to provide insight into the structure of the RNA and origins of the gene. Using DNA methylation of promoter sequences to assess whether genes are silenced in females we report the inactivation status of seven X-linked genes in humans and mice as well as two additional eutherians, the mole and the cow, providing evidence that escape from inactivation is common among Eutheria. PMID- 17728100 TI - Hybrid revascularization using Silverhawk atherectomy and infrapopliteal bypass for limb salvage. AB - Patients with limb-threatening ischemia and a paucity of ipsilateral greater saphenous vein for conduit represent a challenge for lower extremity revascularization. We present four patients with limited autogenous conduit who underwent hybrid revascularization using the Silverhawk atherectomy device and infrapopliteal artery bypass for limb-threatening ischemia. All patients experienced complete wound healing in early follow-up. Hybrid revascularization appears safe, produces excellent short-term outcomes, and may be appropriate for patients with limited autogenous vein who require lower extremity revascularization. PMID- 17728101 TI - In vitro exposure of porcine granulosa cells to the phytoestrogens genistein and daidzein: effects on the biosynthesis of reproductive steroid hormones. AB - Since a discrepancy concerning the effects of phytoestrogens on steroidogenesis exists in the literature we investigated the effects of genistein and daidzein on progesterone and estradiol synthesis in cultured primary granulosa cells derived from follicles of porcine ovaries. In this context, the investigation was performed to test the hypothesis that isoflavones can reduce hydroxysteroid dehydrogenase/isomerase (3beta-HSD) activity by down-regulation of its transcription. We found that daidzein did not impair the viability of cultured granulosa cells in the concentration range from 0.1 to 100 microM, but genistein inhibited the cell viability at 50 microM compared to the unexposed controls. Forskolin (10 microM) and pregnenolone (2.5 microM) enhanced the basal progesterone secretion in the absence of both phytoestrogens. Daidzein or genistein at non-toxic concentrations alone or combined with forskolin or pregnenolone significantly reduced progesterone synthesis. This reduction was not due to changes of the abundance of P450scc protein, but the gene hydroxysteroid dehydrogenase/isomerase (3beta-HSD) was significantly decreased at a non-toxic concentration of daidzein (50 microM) in non-stimulated and pregnenolone stimulated cells. Moreover, genistein (1, 10 microM) significantly inhibited the 3beta-HSD-mRNA only in pregnenolone-stimulated granulosa cells. It can be suggested that the effect of genistein on steroidogenesis only partly results from the impairment of 3beta-HSD gene expression. In non-toxic concentrations daidzein and genistein did not change the androstenedione- or testosterone stimulated estradiol-17beta synthesis. In summary, genistein and daidzein have direct effects on porcine granulosa cell progesterone synthesis which involve the inhibition of 3beta-HSD enzyme activity across the post-cyclic AMP pathway. PMID- 17728099 TI - Winter day lengths enhance T lymphocyte phenotypes, inhibit cytokine responses, and attenuate behavioral symptoms of infection in laboratory rats. AB - Annual variations in day length (photoperiod) trigger changes in the immune and reproductive system of seasonally-breeding animals. The purpose of this study was to determine whether photoperiodic changes in immunity depend on concurrent photoperiodic responses in the reproductive system, or whether immunological responses to photoperiod occur independent of reproductive responses. Here we report photoperiodic changes in enumerative, functional, and behavioral aspects of the immune system, and in immunomodulatory glucocorticoid secretion, in reproductively non-photoperiodic Wistar rats. T-cell numbers (CD3+, CD8+, CD8+CD25+, CD4+CD25+) were higher in the blood of rats housed in short as opposed to long-day lengths for 10 weeks. Following a simulated bacterial infection (Escherichia coli LPS; 125 microg/kg) the severity of several acute-phase sickness behaviors (anorexia, cachexia, neophobia, and social withdrawal) were attenuated in short days. LPS-stimulated IL-1beta and IL-6 production were comparable between photoperiods, but plasma TNFalpha was higher in long-day relative to short-day rats. In addition, corticosterone concentrations were higher in short-day relative to long-day rats. The data are consistent with the hypothesis that photoperiodic regulation of the immune system can occur entirely independently of photoperiodic regulation of the reproductive system. In the absence of concurrent reproductive responses, short days increase the numbers of leukocytes capable of immunosurveillance and inhibition of inflammatory responses, increase proinflammatory cytokine production, increase immunomodulatory glucocorticoid secretion, and ultimately attenuate behavioral responses to infection. Seasonal changes in the host immune system, endocrine system, and behavior may contribute to the seasonal variability in disease outcomes, even in reproductively non-photoperiodic mammals. PMID- 17728103 TI - 14-3-3epsilon inhibits MK5-mediated cell migration by disrupting F-actin polymerization. AB - The signal pathway by which 14-3-3epsilon inhibits cell migration induced by MAPK activated protein kinase 5 (MK5) was investigated in cultured HeLa cells. Both in vivo and in vitro analyses have revealed that 14-3-3epsilon interacts with MK5. 14-3-3epsilon bound to MK5 inhibits the phosphorylation of HSP27, a known substrate of MK5. Disturbance of actin cytoskeleton organization by 14-3-3epsilon was shown in transfected cells transiently expressing 14-3-3epsilon as well as established cells stably expressing 14-3-3epsilon. Moreover, overexpression of 14 3-3epsilon resulted in the inhibition of cell migration induced by MK5 overexpression or TNFalpha treatment. Our results suggest that 14-3-3epsilon bound to MK5 inhibits cell migration by inhibiting the phosphorylation of HSP27 whose phosphorylation regulates F-actin polymerization, actin cytoskeleton organization and subsequent actinfilament dynamics. PMID- 17728102 TI - ROCK I-mediated activation of NF-kappaB by RhoB. AB - RhoB is a short-lived protein whose expression is increased by a variety of extra cellular stimuli including UV irradiation, epidermal growth factor (EGF) and transforming growth factor beta (TGF-beta). Whereas most Rho proteins are modified by the covalent attachment of a geranylgeranyl group, RhoB is unique in that it can exist in either a geranylgeranylated (RhoB-GG) or a farnesylated (RhoB-F) form. Although each form is proposed to have different cellular functions, the signaling events that underlie these differences are poorly understood. Here we show that RhoB can activate NF-kappaB signaling in multiple cell types. Whereas RhoB-F is a potent activator of NF-kappaB, much weaker activation is observed for RhoB-GG, RhoA, and RhoC. NF-kappaB activation by RhoB is not associated with increased nuclear translocation of RelA/p65, but rather, by modification of the RelA/p65 transactivation domain. Activation of NF-kappaB by RhoB is dependent upon ROCK I but not PRK I. Thus, ROCK I cooperates with RhoB to activate NF-kappaB, and suppression of ROCK I activity by genetic or pharmacological inhibitors blocks NF-kappaB activation. Suppression of RhoB activity by dominant-inhibitory mutants, or siRNA, blocks NF-kappaB activation by Bcr, and TSG101, but not by TNFalpha or oncogenic Ras. Collectively, these observations suggest the existence of an endosome-associated pathway for NF kappaB activation that is preferentially regulated by the farnesylated form of RhoB. PMID- 17728105 TI - Anticonvulsant enaminone E139 suppresses epileptiform activity in rat hippocampal slices. AB - Some enaminones are reported to have in vivo anticonvulsant activity. We asked if methyl 4-(4'-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate (E139), one of such enaminones produced in vitro effects that may underlie or explain these in vivo anticonvulsant actions by testing if E139 suppressed in vitro seizures. In vitro seizures were generated chemically in hippocampal slices using picrotoxin and zero Mg(2+) buffer and electrically by high frequency stimulation (HFS). E139 (10 microM) depressed evoked field population spike (PS) amplitude by -28.6+/ 4.5% (n=5), an effect that was blocked by 1 microM CGP55845 (2.7+/-5.5%, n=6). Picrotoxin (100 microM) transformed single PS into multiple PS (4.5+/-0.2, n=5) and E139 reversibly reduced the number of these multiple PS by -23.4+/-1.8% (n=5). Similarly, zero Mg(2+) buffer produced multiple spikes (3.6+/-0.6, n=5) that were suppressed by E139 (-54.8+/-9.7%, n=5). This effect was also blocked by CGP55845 (2.3+/-5.7%, n=6). Furthermore, E139 suppressed the frequency of spontaneous bursts (SB) that were recorded in zero Mg(2+) by -65.8+/-10.5% (n=12). CGP55845 significantly reduced this E139-induced SB suppression (-21.7+/ 9.6%, n=6). In the electrical model, afterdischarges (AD) and SB recorded in area CA3 after a pattern of HFS (100Hz) were suppressed by E139 (-48.6+/-14.3% and 66.7+/-6.7%, respectively, n=6). These E139 effects on AD and SB were reduced, but not completely blocked, by CGP55845 (-32.1+/-5.3% and -44.4+/-9.7%, respectively, n=7). Finally, pretreatment of slices with E139 did not prevent zero Mg(2+)-induced multiple spikes and SB. We conclude that E139 suppresses in vitro seizures in the hippocampus by synaptic and non-synaptic mechanisms. These actions on network activity may underlie their reported in vivo anticonvulsant effects. PMID- 17728104 TI - Ethanol induces apoptosis in hepatocytes by a pathway involving novel protein kinase C isoforms. AB - Ethanol abuse is one of the major etiologies of cirrhosis. Ethanol has been shown to induce apoptosis via activation of oxidative stress, mitogen-activated protein kinases (MAPK), and tyrosine kinases. However, there is a paucity of data that examine the interplay among these molecules. In the present study we have systematically elucidated the role of novel protein kinase C isoforms (nPKC; PKCdelta and PKCepsilon) in ethanol-induced apoptosis in hepatocytes. Ethanol enhanced membrane translocation of PKCdelta and PKCepsilon, which was associated with the phosphorylation of p38MAPK, p42/44MAPK and JNK1/2, and the nuclear translocation of NF-kappaB and AP-1. This resulted in increased apoptosis in primary rat hepatocytes. Inhibition of both PKCdelta and PKCepsilon resulted in a decreased MAPK activation, decreased nuclear translocation of NF-kappaB and AP-1, and inhibition of apoptosis. In addition, ethanol activated the tyrosine phosphorylation of PKCdelta via tyrosine kinase in hepatocytes. The tyrosine phosphorylated PKCdelta was cleaved by caspase-3 and these fragments were translocated to the nucleus. Inhibition of ethanol-induced oxidative stress blocked the membrane translocation of PKCdelta and PKCepsilon, and the tyrosine phosphorylation of PKCdelta in hepatocytes. Inhibition of oxidative stress, tyrosine kinase or caspase-3 activity caused a decreased nuclear translocation of PKCdelta in response to ethanol, and was associated with less apoptosis. CONCLUSION: These results provide a newly-described mechanism by which ethanol induces apoptosis via activation of nPKC isoforms in hepatocytes. PMID- 17728107 TI - Optimal management of urosepsis from the urological perspective. AB - Urosepsis in adults comprises approximately 25% of all sepsis cases and in most cases is due to complicated urinary tract infections (UTIs). In this paper we review the optimal management of urosepsis from the urological point of view. Urosepsis is often due to obstructed uropathy of the upper or lower urinary tract. The treatment of urosepsis comprises four major aspects: 1. Early goal directed therapy; 2. Optimal pharmacodynamic exposure to antimicrobials both in blood and in the urinary tract; 3. Control of complicating factors in the urinary tract; 4. Specific sepsis therapy. Early tissue oxygenation, appropriate initial antibiotic therapy and rapid identification and control of the septic focus in the urinary tract are critical steps in the successful management of a patient with severe urosepsis. To achieve this goal an optimal interdisciplinary approach encompassing the emergency unit, urological specialties and intensive-care medicine is necessary. PMID- 17728106 TI - Cognition, functioning and quality of life in schizophrenia treatment: results of a one-year randomized controlled trial of olanzapine and quetiapine. AB - BACKGROUND: Cognitive deficits are recognized as a critical determinant of functional outcomes in schizophrenia; and second generation antipsychotic drugs have been touted for their potential to enhance cognitive functioning and community tenure. OBJECTIVES: The study examined the relative merits of olanzapine and quetiapine in improving cognitive deficits and enhancing psychosocial functioning in a sample of community dwelling adults previously treated with first generation antipsychotic drugs for schizophrenia. METHODS: In a prospective, rater-blinded study, 86 participants were randomized to receive either olanzapine or quetiapine, and assessed at baseline and after 3, 6, 9 and 12 months. Outcome measures included, besides symptoms and side effects rating scales, the subjective scale to investigate cognition in schizophrenia (SSTICS), a computer-assisted cognitive test battery (COGLAB), the sickness impact profile (SIP), the global assessment of functioning (GAF) scale, and the drug attitude inventory (DAI). RESULTS: Both olanzapine and quetiapine were equally effective in improving symptom severity and decreasing the neurological side effects. Quetiapine was significantly better tolerated (p=0.002), improved self-rated cognitive dysfunction (p=0.002) and subjects' performance on selected neurocognitive tasks (p=0.01). Olanzapine use was associated with greater symptom stability, fewer drop outs (p=0.01) and frequent metabolic aberrations (p=0.001). The accrued benefits of drug therapy, however, were not reflected as significant gains in daily functioning and quality of life. CONCLUSIONS: Quetiapine is noted to have specific cognition enhancing properties in schizophrenia that warrants further exploration. The observed clinical and cognitive benefits associated with quetiapine may likely be attributable to its loose binding to, and fast dissociation from the dopamine receptors. Olanzapine has proved to be a reliable antipsychotic drug with a greater liability to cause metabolic abnormalities. PMID- 17728109 TI - Nitric oxide involvement in the antidepressant-like effects of acute lithium administration in the mouse forced swimming test. AB - In the present study we evaluated the involvement of l-arginine/nitric oxide (NO)/cGMP pathway in the antidepressant-like effects of acute lithium administration in the mouse forced swimming test (FST). Lithium, at 30 and 100 mg/kg, significantly reduced the immobility times of mice in the FST, whereas at lower doses (0.5, 5 and 10 mg/kg) had no effect on the immobility time. The NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), at 10 and 30 mg/kg, and the selective neuronal NOS inhibitor N(omega)-propyl-L-arginine (L NPA), at 5 and 15 mg/kg, had no significant effects on the FST, whereas they significantly decreased the immobility time at 100 and 30 mg/kg, respectively. Combination of non-effective dose of lithium (10 mg/kg) with low doses of L-NAME (30 mg/kg) or L-NPA (15 mg/kg) significantly reduced the immobility times in the FST. Moreover, the guanylyl cyclase inhibitor ODQ at 50 mg/kg significantly decreased the immobility time of mice, whereas it had not significant effects on the FST at 2, 10 and 20 mg/kg. Combination of lithium (10 mg/kg) with 20 mg/kg ODQ significantly decreased the immobility times in the FST. Non-effective doses of L-arginine (750 mg/kg) or sildenafil (5 mg/kg) significantly reversed the antidepressant-like effect of 30 mg/kg lithium in the FST. Neither of the drugs had effect on the locomotor activity. These data indicate the involvement of L arginine/NO/cGMP pathway in the antidepressant-like effect of lithium in the mouse FST and also might suggest the concurrent administration of NOS inhibitors and lithium as an appropriate strategy for treatment of depression. PMID- 17728108 TI - Norchloro-fluoro-homoepibatidine (NCFHEB) - a promising radioligand for neuroimaging nicotinic acetylcholine receptors with PET. AB - Cholinergic neurotransmission depends on the integrity of nicotinic acetylcholine receptors (nAChRs), and impairment of both is characteristic for various neurodegenerative diseases. Visualization of specific receptor subtypes by positron emission tomography (PET) has potential to assist with diagnosis of such neurodegenerative diseases and with design of suitable therapeutic approaches. The goal of our study was to evaluate in vivo the potential of (18)F-labelled (+) and (-)-norchloro-fluoro-homoepibatidine ([(18)F]NCFHEB) in comparison to 2 [(18)F]F-A-85380 as PET tracers. In the brains of NMRI mice, highest levels of radioactivity were detected at 20 min post-injection of (+)-[(18)F]NCFHEB, (-) [(18)F]NCFHEB, and 2-F-[(18)F]-A-85380 (7.45, 5.60, and 3.2% ID/g tissue, respectively). No marked pharmacological adverse effects were observed at 25 mug NCFHEB/kg. Uptake studies in RBE4 cells and in situ perfusion studies suggest an interaction of epibatidine and NCFHEB with the carrier-mediated choline transport at the blood-brain barrier. The data indicate that (+)- and (-)-[(18)F]NCFHEB have potential for further development as PET tracers. PMID- 17728110 TI - Addition of memantine to antipsychotic treatment in schizophrenia inpatients with residual symptoms: A preliminary study. AB - BACKGROUND: Schizophrenia is comprised of several debilitating symptoms. Antipsychotics offer an effective treatment for positive symptoms, while the negative signs and cognitive deficits are usually treatment-resistant. It was suggested that glutamate dysregulation may be involved in the neuropathology of schizophrenia, mainly through NMDA dysfunction. We hypothesized that addition of memantine, a weak non-selective NMDA receptor antagonist approved for dementia, to antipsychotics would improve the clinical status of un-remitted schizophrenia patients, notably the negative signs and cognitive deficits. METHODS: Seven schizophrenia patients, were included in a six-week open-label study, with weekly increasing dosage (5, 10, 15, 20 mg) of memantine added to their on-going antipsychotic treatment. RESULTS: We found a significant improvement of the PANSS score (baseline 116.28+/-21.9 vs. 97.86+/-24.48 after six weeks, t=5.98, p<0.001) with the most prominent improvement (21%) in negative signs sub-scale (baseline 40+/-6.38 vs. 31.71+/-7.76 after six weeks, t=5.87, p<0.001). Cognitive status, measured with the Neurobehavioral Cognitive Examination (NCSE) and Clock Drawing Test (CDT) showed no improvement. CONCLUSION: Memantine addition to antipsychotic treatment, in schizophrenia patients might improve their clinical status, primarily the negative signs, but not their cognitive deficits. Further research is needed to replicate these observations. PMID- 17728111 TI - 5-HT1A receptors in the dorsal hippocampus mediate the anxiogenic effect induced by the stimulation of 5-HT neurons in the median raphe nucleus. AB - We evaluated the involvement of dorsal hippocampus (DH) 5-HT1A receptors in the mediation of the behavioral effects caused by the pharmacological manipulation of 5-HT neurons in the median raphe nucleus (MRN). To this end, we used the rat elevated T-maze test of anxiety. The results showed that intra-DH injection of the 5-HT1A/7 agonist 8-OH-DPAT facilitated inhibitory avoidance, an anxiogenic effect, without affecting escape. Microinjection of the 5-HT1A antagonist WAY 100635 was ineffective. In the elevated T-maze, inhibitory avoidance and escape have been related to generalized anxiety and panic disorders, respectively. Intra MRN administration of the excitatory amino acid kainic acid, which non selectively stimulates 5-HT neurons in this brain area facilitated inhibitory avoidance and impaired escape performance, but also affected locomotion. Intra MRN injection of WAY-100635, which has a disinhibitory effect on the activity of 5-HT neurons in this midbrain area, only facilitated inhibitory avoidance. Pre administration of WAY-100635 into the DH blocked the behavioral effect of intra MRN injection of WAY-100635, but not of kainic acid. These results indicate that DH 5-HT1A receptors mediate the anxiogenic effect induced by the selective stimulation of 5-HT neurons in the MRN. PMID- 17728113 TI - Impaired facial emotion recognition and reduced amygdalar volume in schizophrenia. AB - Structural abnormalities of the amygdala and impaired facial emotion recognition have been reported in schizophrenia. Most studies demonstrated reduced amygdalar volumes in schizophrenia patients, and difficulty in recognizing negative facial emotions has also been reported. However, findings on the deficit in facial emotion recognition have been inconsistent, and the relationships between this impairment and amygdalar volume reduction remain unclear. In this study, we investigated these relationships by performing volumetric analysis of the amygdala and evaluation of facial emotion recognition performance in the same subjects with schizophrenia. The sample group comprised 20 schizophrenia patients and 20 matched healthy controls. We measured the volumes of the amygdalae with high-resolution magnetic resonance imaging (MRI) at 3.0 Tesla. Additionally, we included a task that evaluated the subjects' ability to recognize the intensity of basic facial emotions. We found that impaired facial emotion recognition in schizophrenia patients is emotion-specific (sadness, surprise, disgust, and anger). Moreover, the volume of each amygdala on either side of the brain was reduced. Finally, we found a correlation between left amygdalar volume and the recognition of sadness in facial expressions. This study demonstrated that amygdala dysfunction may contribute to impaired facial emotion recognition in schizophrenia. PMID- 17728114 TI - 93Nb and 17O NMR chemical shifts of niobiophosphate compounds. AB - Niobiophosphate compounds with a large range of niobium and oxygen environments were studied with (93)Nb and (17)O solid-state NMR. (93)Nb isotropic chemical shift of pure niobate Nb(ONb)(6), pure phosphate Nb(OP)(6) and mixed phosphate niobate Nb(OP)(x)(ONb)((6-x)) (122 repeats were more frequent in cases than in controls, being associated with an increased risk of BC (OR=1.49; CI(95%)=1.06-2.09; p=0.021). No significant differences were found for categorised GGN(n). For CAG(n)/GGN(n) combinations, the highest BC risk was found to be associated with the CAG(n)>22/GGN(n)24 combination (OR=2.47; CI(95%)=1.37 4.46; p=0.003). In conclusion, our results indicate that longer CAG(n)/GGN(n) combinations increase the risk of BC and suggest that CAG and GGN AR polymorphisms should be considered in order to assess the BC risk. PMID- 17728128 TI - Desulfurization of various organic sulfur compounds and the mixture of DBT + 4,6 DMDBT by Mycobacterium sp. ZD-19. AB - A new isolated dibenzothiophene (DBT) desulfurizing bacterium, identified as Mycobacterium sp. ZD-19 can utilize a wide range of organic sulfur compounds as a sole sulfur source. Thiophene (TH) or benzothiophene (BTH) was completely degraded by strain ZD-19 within 10h or 42 h, and 100% DBT or 4,6 dimethyldibenzothiophene (4,6-DMDBT) was removed within 50h or 56 h, respectively. Diphenylsulfide (DPS) possessed the lowest desulfurization efficiencies with 60% being transformed within 50h and 80% at 90 h. The desulfurization activities of five substrates by resting cells are in order of TH>BTH>DPS>DBT>4,6-DMDBT. In addition, when DBT and 4,6-DMDBT were mixed, they could be simultaneously desulfurized by strain ZD-19. However, DBT appeared to be attacked prior to 4,6-DMDBT. The desulfurization rate of DBT or 4,6-DMDBT in mixture is lower than they are desulfurized separately, indicating that the substrate competitive inhibition is existent when DBT and 4,6-DMDBT are mixed. PMID- 17728129 TI - Enhanced production of exocellular glucansucrase from Leuconostoc dextranicum NRRL B-1146 using response surface method. AB - Statistically-based experimental designs were applied to optimize the fermentation for the production of glucosyltransferase by Leuconostoc dextranicum NRRL B-1146. Eleven medium components were examined for their significance on enzyme production using Plackett-Burman factorial design. Tween 80, sucrose and K2HPO4 significantly improved the enzyme production process. The combined effect of these nutrients on glucansucrase production were studied using a 2 2 full factorial central composite design, a second-order polynomial was established to identify the relationship between the enzyme output and the three medium components. The optimal concentration of variables for maximum glucansucrase production were Tween 80 (0.55%, v/v); sucrose (5.6%, w/v) and K2HPO4 (1%, w/v). The maximum enzyme activity by predicted model was 6.53 U/ml that was in perfect agreement with the actual experimental value (6.40 U/ml). PMID- 17728130 TI - 2-O-carboxymethylpyrogallol derivatives as PTP1B inhibitors with antihyperglycemic activity. AB - 2-O-carboxymethylpyrogallol derivatives (4-17) were synthesized, with their in vitro inhibitory activities against PTP1B and in vivo antihyperglycemic effects examined. Compound 14, the most potent among the series, showed a K(i) value of 1.1 microM against PTP1B, 7-fold lower than that against TC-PTP. When compound 14 was fed to a high-fat diet-induced diabetic mouse model, significant improvements were observed in both the fasting glucose level and glucose tolerance. PMID- 17728131 TI - Synthesis and application of 2'-fluoro-substituted cap analogs. AB - Design, synthesis, and biological evaluation of 2'-fluoro-substituted cap analogs, i.e., m(7,2'F)G[5']ppp[5']G and m(7,2'F)G[5']ppp[5']m(7)G are described. Structures were confirmed by (1)H, (31)P, (19)F NMR and MS data. The effects of the 2'-fluoro-substituted moiety from the normal and N(7) double methylated mCAP were evaluated with respect to their capping efficiency, in vitro T7 RNA polymerase transcription efficiency, and translation activity using cultured HeLa cells. Luciferase fusion protein production was monitored by measuring the luciferase activity. mRNA poly(A) capped with 2'-fluoro-substituted cap analogs, (m(7,2'F)G[5']ppp[5']G) and (m(7,2'F)G[5']ppp[5']m(7)G), were translated approximately 2.4- and 2.5-fold more efficiently, respectively, than mRNA capped with conventional m(7)G[5']ppp[5']G. PMID- 17728132 TI - Alkanethiol containing glycopolymers: a tool for the detection of lectin binding. AB - Glycopolymers are useful macromolecules with a non-carbohydrate backbone for presenting saccharides in multivalent form. Here, glycopolymers containing mannose and alkanethiol linker were synthesized through substituting preactivated poly [N-(acryloyloxy) succinimide] (pNAS) with amine-containing monomer. With the obtained glycopolymers, a glycosurface was generated on the gold surface of quartz crystal microbalance (QCM) through self-assembled strategy by the use of alkanethiol functional group. Furthermore, the resulting glycosurface was used to detect the binding of mannose specific lectin concanavalin A (Con A). PMID- 17728133 TI - Adjuvant treatment of elderly breast cancer patients. AB - Increasing age is the major risk factor for breast cancer. About half of all new breast cancers and more than half of breast cancer deaths in affluent nations occur in women 65 years and older. Endocrine therapy with aromatase inhibitors or tamoxifen is appropriate adjuvant therapy for older women with life expectancies of greater than 5 years and hormone receptor positive tumors. The greatest benefit of adjuvant chemotherapy is in elders with hormone receptor negative, node positive, or high-risk node negative tumors. The effect of co-morbidity on survival must be factored into all adjuvant therapy decisions and newer validated tools can accurately estimate non-breast cancer related survival. Age bias still exists and results in frequent undertreatment of older women and compromised survival. Elders remain under-represented in clinical trials and should be encouraged to participate. Health care providers as well as government leaders and patients need to be educated on cancer in elders. PMID- 17728135 TI - Fibrin glue in coronary surgery. PMID- 17728134 TI - Development of Tyrocidine A analogues with improved antibacterial activity. AB - The development of new antibacterial therapeutic agents capable of halting microbial resistance is a chief pursuit in clinical medicine. Classes of antibiotics that target and destroy bacterial membranes are attractive due to the decreased likelihood that bacteria will be able to generate resistance to this mechanism. The amphipathic cyclic decapeptide, Tyrocidine A, is a model for this class of antibiotics. Tyrocidine A is composed of a hydrophobic and a hydrophilic face, allowing for insertion into bacterial membranes, creating porous channels and destroying membrane integrity. We have used a combination of molecular modeling and solid phase synthesis to prepare Tyrocidine A and analogues 1-8. The minimum inhibitory concentrations (MICs) of these compounds were determined for a host of gram positive species and E. coli as a representative gram negative bacterium. Analogues 2 and 5 demonstrated moderate 2- to 8-fold increases in antibacterial activity over the parent Tyrocidine A for a variety of pathogenic microbes (best MICs for E. coli 32 microg/mL and 2 microg/mL for most gram positives). Examination of the structure- activity relationship between the analogues demonstrated a preference for increased amphipathicity but did not show a clear preference for increasing hydrophilicity versus hydrophobicity in improving antibacterial activity. Of note, movement of positively charged lysine residues or neutral pentafluorophenyl residues to different positions within the cyclopeptide ring system demonstrated improvements in antibacterial activity. PMID- 17728136 TI - Time-dependent responses of wounded human skin fibroblasts following phototherapy. AB - BACKGROUND AND OBJECTIVE: The penetration and distribution of laser light in target tissue is dependent on the wavelength of the light. One problem with most of the published data on laser irradiation is that most studies do not record the duration between the exposure and the evaluation. This study aimed to establish if the dose, wavelength or duration of effect (1h or 24h) influences the biological responses of irradiated fibroblasts. MATERIALS AND METHODS: The study established cellular responses of normal and wounded human skin fibroblasts to helium-neon (632.8 nm), diode (830 nm) and Nd:YAG (1064 nm) laser irradiation using one exposure of 5 J/cm(2) or 16 J/cm(2) on day 1 and again on day 4. Cellular responses to laser irradiation were evaluated by measuring changes in cell viability (ATP viability and caspase 3/7 activity) and cell proliferation (ALP enzyme activity and bFGF expression), 1h and 24h post irradiation. RESULTS: Wounded cells exposed to 5 J/cm(2) using 632.8 nm showed an increase in ATP viability after 1h, a decrease in caspase 3/7 activity after 24h and an increase in cell proliferation after 24h. The results suggest that changes in parameters such as ATP viability should be observed directly after laser irradiation (1h) whereas other parameters such as caspase 3/7 activity, bFGF expression and ALP enzyme activity should be measured at least 24h after the final exposure. CONCLUSION: This study confirms that the duration of effect should be included as one of the main laser parameters when reporting on the effects of laser irradiation. It is important to establish time-dependent responses as the results may provide an understanding of the cellular responses following laser irradiation. PMID- 17728137 TI - Opposite effects of bFGF and TGF-beta on collagen metabolism by human periodontal ligament fibroblasts. AB - This study evaluated the effects of bFGF and TGF-beta, individually and combined, on cell proliferation and collagen metabolism. Primary human periodontal ligament cells were stimulated with two concentrations (1 and 10 ng/ml) of each growth factor, both individually and combined. Proliferation was determined by a commercial biochemical assay. Real time RT-PCR determined gene expression of MMP 1 and -2, collagen types I and III, TIMP-1, -2 and -3. Autocrine effects on synthesis of bFGF and TGF-beta were evaluated by ELISA. Only TGF-beta, either isolated or associated with bFGF, significantly increased cell proliferation. TGF beta had anabolic effects, increasing expression of type I and III collagen as well as of TIMPs, whereas bFGF had opposite effects. When bFGF and TGF-beta were associated, the anabolic effects prevailed. Synthesis of TGF-beta was induced only by the association of lower concentrations of the growth factors, whereas there was a dose-dependent production of bFGF. It is concluded that bFGF had a predominantly catabolic effect, and TGF-beta exerted an anabolic effect on hPDL cells. PMID- 17728138 TI - Development of a dielectric barrier discharge ion source for ambient mass spectrometry. AB - A new ion source based on dielectric barrier discharge was developed as an alternative ionization source for ambient mass spectrometry. The dielectric barrier discharge ionization source, termed as DBDI herein, was composed of a copper sheet electrode, a discharge electrode, and a piece of glass slide in between as dielectric barrier as well as sample plate. Stable low-temperature plasma was formed between the tip of the discharge electrode and the surface of glass slide when an alternating voltage was applied between the electrodes. Analytes deposited on the surface of the glass slide were desorbed and ionized by the plasma and the ions were introduced to the mass spectrometer for mass analysis. The capability of this new ambient ion source was demonstrated with the analysis of 20 amino acids, which were deposited on the glass slide separately. Protonated molecular ions of [M + H](+) were observed for all the amino acids except for L-arginine. This ion source was also used for a rapid discrimination of L-valine, L-proline, L-serine and L-alanine from their mixture. The limit of detection was 3.5 pmol for L-alanine using single-ion-monitoring (SIM). Relative standard deviation (RSD) was 5.78% for 17.5 nmol of L-alanine (n = 5). With the advantages of small size, simple configuration and ease operation at ambient conditions, the dielectric barrier discharge ion source would potentially be coupled to portable mass spectrometers. PMID- 17728139 TI - Semaphorin3A accelerates neuronal polarity in vitro and in its absence the orientation of DRG neuronal polarity in vivo is distorted. AB - Axon guidance cues are critical for neuronal circuitry formation. Guidance molecules may repel or attract axons directly by effecting growth cone motility, or by impinging on neuronal polarity. In Semaphorin3A null mice, many axonal errors are detected, most prominently in DRG neurons. It has been generally assumed the repellent properties of Semaphorin3A are the cause of these erroneous axonal projections. Here we show that, in semaphorin3A-null mice, the initial trajectory of neurons in the DRG is abnormal, suggesting that Semaphorin3A may instruct neuronal polarity. In corroboration, in vitro Semaphorin3A dramatically increases neuronal polarization, as indicated by GSK3beta and Rac1 sub-cellular localization in DRG neurons. Polarization effects of Semaphorin3A are regulated by activated MAPK, as indicated by p-MAPK 42/44 polarization and the need for its activity for Rac1 and GSK3beta polarization. Taken together, our findings suggest that Semaphorin3A plays a role in the formation of neuronal polarity, in addition to its classic repellent role. PMID- 17728140 TI - Antidepressants induce cellular insulin resistance by activation of IRS-1 kinases. AB - Certain selective serotonin reuptake inhibitors (SSRIs) induce the clinical and biochemical manifestations of a metabolic syndrome by as yet unknown mechanism. Here we demonstrate that incubation (1 h) of rat hepatoma Fao cells with the SSRIs paroxetine and sertraline, but not with the atypical antipsychotic drug olanzapine, inhibited the insulin-stimulated Tyr phosphorylation of the insulin receptor substrate-1 (IRS-1) with half-maximal effects at approximately 10 microM. This inhibition correlated with a rapid phosphorylation and activation of a number of Ser/Thr IRS-1 kinases including JNK, S6K1, ERK and p38 MAPK, but not PKB (Akt). JNK appears as a key player activated by SSRIs because specific JNK inhibitors partially eliminated the effects of these drugs. The SSRIs induced the phosphorylation of IRS-1 on S307 and S408, which inhibits IRS-1 function and insulin signaling. These results implicate selected SSRIs as inhibitors of insulin signaling and as potential inducers of cellular insulin resistance. PMID- 17728141 TI - Mechanism of MASH1 induction by ASK1 and ATRA in adult neural progenitors. AB - The molecular mechanisms underlying differentiation and lineage commitment in neural stem cells are just beginning to be understood, however the molecules involved in this process and their functions remain largely unknown. Here we studied the effects and downstream signals of apoptosis signal-regulating kinase 1 (ASK1) together with all-trans retinoic acid (ATRA) on neuronal differentiation in adult hippocampus-derived progenitor (AHP) cells. Following ASK1 over expression and ATRA treatment in AHPs, a larger number of cells differentiated into neurons and the MASH1 promoter became activated. Analyzing downstream effector molecules of ASK1 or ATRA targeting the MASH1 promoter revealed that the myocyte enhancer factor 2C (MEF2C) mediated ASK1 signalling, while activation of Sp1 was involved in ATRA signalling. Chromatin immunoprecipitation assay on the promoter revealed that ASK1 induced binding of MEF2C and Ca(2+)/calmodulin dependent kinase II to the MASH1 promoter. Taken together, ASK1 and ATRA activate MEF2C and Sp1, respectively, and up-regulate MASH1 protein expression. PMID- 17728142 TI - A simple and rapid method for quantifying 2-phenoxyethanol (2-PE) in Diphtheria, Tetanus and w-Pertussis (DTwP) vaccine. AB - The authors developed a simple and rapid method for quantitation of 2 phenoxyethanol (2-PE) in DTwP vaccine based on reverse phase high performance liquid chromatography (HPLC). The method was simple and reproducible. The sensitivity of the assay was confirmed by spiking known amounts of 2 phenoxyethanol to the vaccine sample. PMID- 17728143 TI - Characterization of a complex glycoprotein whose variable metabolic clearance in humans is dependent on terminal N-acetylglucosamine content. AB - Glycoproteins can be cleared from circulation if they carry oligosaccharide structures that are recognized by specific receptors. High-mannose type and asialo complex oligosaccharides are cleared by the mannose and asialoglycoprotein receptors, respectively. This paper presents the protein and terminal saccharide characterization for nine batches of a glycoprotein developed for pharmaceutical use. Each of these batches was evaluated in human pharmacokinetic (PK) studies, and had similar terminal elimination half-lives, but the initial clearance of this glycoprotein varied between batches. The protein is lenercept, an immunoadhesin comprising the Fc domain of human IgG1 and two tumor necrosis factor (TNF) binding domains derived from the extracellular portion of the TNFR1(p55). Lenercept is manufactured in Chinese hamster ovary (CHO) cells and is extensively N-glycosylated but is devoid of high-mannose glycans. The pharmacokinetic variability between these lots only correlated with terminal N acetylglucosamine and not with terminal galactose, sialic acid or any polypeptide related parameter. The data emphasize the need for appropriate analytical methods for the characterization of glycoproteins, especially those designed for long half-lives, and show that assessment of the content of all three terminal saccharides is sufficient to ensure consistency of their PK performance properties. PMID- 17728145 TI - An incident case-control study of modes of hepatitis C virus transmission in France. AB - PURPOSE: Risk factors for hepatitis C virus (HCV) infection have rarely been estimated using incident case-control studies in the "general" population. We undertook a case-control study of incident HCV infection to identify persistent modes of transmission in France. METHODS: Two types of case-patients were included: (1) repeat blood donors who seroconverted between 1998 and 2001 (with a last negative third-generation test reported from 1995 or after) and (2) seroconverters referred to hepatology departments in 2000 through 2001. For each case-patient, four age- and sex-matched controls were randomly selected from the population of occurrence. Data on risk factors were recorded for each case patient's and matched control's referent exposure period (between last negative and first positive tests). RESULTS: Sixty-four case-patients and 227 controls were included. In univariate analysis, endoscopy (matched odds ratios [mORs] = 8.0; 95% confidence intervals [CI] = 2.3-27.2), general anesthesia (mOR = 5.6; 95% CI = 2.2-14.7), tattooing or body piercing (mOR = 8.8; 95% CI = 1.7-44.1), and intravenous (IV) drug use (p < 0.0001; mOR not defined) were associated with HCV seroconversion. In multivariate analysis, risk factors associated with HCV seroconversion were drug use (adjusted OR [aOR] = 109.0; 95% CI = 11.7-1015.8), digestive endoscopy (aOR = 5.7; CI = 1.4-23.8), and invasive radiology procedures (aOR = 11.6; CI = 1.7-78.5). CONCLUSIONS: The results showed the continuing major role of IV drug use and suggested that transmission related to invasive health care remained a potential source of new HCV infection between 1995 and 2001. PMID- 17728144 TI - A hollow-fiber bioreactor for expanding HIV-1 in human lymphocytes used in preparing an inactivated vaccine candidate. AB - An inactivated HIV vaccine intended to elicit broadly neutralizing antibodies is designed to use a pool of population-prevalent HIV-1 from plasma (PHIV), isolated before evolution of antibody-mediated genetic mutations. A suitable cell substrate (CS) for isolating such PHIV is peripheral blood mononuclear cells (PBMC) after stimulating with phytohemagglutinin (PHA) and interleukin-2 (IL-2). Feasibility of employing a hollow-fiber bioreactor under optimized conditions was investigated for large-scale expansion and efficient recovery of concentrated PHIV. Each CS batch was infected in vitro with a prototype PHIV, the infected cells were introduced into the bioreactor for 7-10 days in co-culture, and the cell-free supernatants were assayed for p24 antigen as an index of HIV synthesis. PBMC versus CD8-depleted (CD8D) CS, 20kDa versus 5kDa molecular weight cut-off (MWCO) bioreactor cartridges, 7- versus 10-day culture periods, and varying concentrations of IL-2, fetal bovine serum (FBS) and glucose content in the medium were functionally evaluated for p24 yield. PBMC cultures in 20kDa MWCO cartridges with 15% FBS, 80IU/mL IL-2 and 2.0g/L glucose produced the highest p24 yield; however, CD8D-CS, 20-30% FBS and 80 IU/mL IL-2 within 5kDa cartridges and 2.0 g/L glucose in the circulating medium was more cost-effective for synthesis of virion p24. PMID- 17728146 TI - Regarding "male and female circumcision associated with prevalent HIV infection in virgins and adolescents in Kenya, Lesotho, and Tanzania". PMID- 17728147 TI - CYP1A1 gene polymorphisms in modifying the association between passive smoking and primary dysmenorrhea. AB - PURPOSE: This study investigated whether the association between passive smoking exposure and primary dysmenorrhea is modified by two susceptibility genes, cytochrome P450 1A1 (CYP1A1)MspI and CYP1A1HincII. METHODS: We recruited 1645 female textile workers from 1997 to 2000 in Anqing, China, collecting information about passive smoking and status of primary dysmenorrhea and taking blood samples. We analyzed the association of CYP1A1 gene polymorphisms and passive smoking exposure with primary dysmenorrhea using multiple logistic regression. RESULTS: In the passive smoking group, women who had the C/C6235 genotype (odds ratio [OR] = 1.8; 95% confidence intervals [CI] = 1.0-3.3) in CYP1A1MspI and Ile/Ile462 genotype (OR = 2.9; 95% CI = 1.1-7.7) in CYP1A1HincII had increased risk of dysmenorrhea. When stratified by genotype, the adjusted OR of dysmenorrhea was 1.6 (95% CI = 1.2-2.1) for the passive smoking group with the Ile/Ile462 genotype and 1.5 (95% CI = 1.0-2.1) with the C/C6235 genotype, compared with the nonpassive smoking group. The data further showed that there was a significant combined effect between passive smoking and the CYP1A1MspI C/C6235 and HincII Ile/Ile462 genotypes (OR = 2.4; 95% CI = 1.2-4.9). CONCLUSIONS: CYP1A1MspI and HincII genotypes modified the association between passive smoking and primary dysmenorrhea. PMID- 17728148 TI - Low bone mineral density, coronary heart disease, and stroke mortality in men and women: the Third National Health and Nutrition Examination Survey. AB - PURPOSE: The aim of this study is to determine the long-term association of bone mineral density and cardiovascular disease mortality. METHODS: The data used are from the Third National Health and Nutrition Examination Survey (NHANES III), a nationally representative sample of noninstitutionalized civilians. A cohort of white, black, and Mexican-American persons ages 50 years and older at baseline (1988-1994) was followed through 2000 for coronary heart disease (CHD; n = 4690) and stroke mortality (n = 5272) using the NHANES III Linked Mortality File. RESULTS: Death certificates were used to identify 369 CHD and 166 stroke deaths. Results were evaluated to determine the relative risk of CHD or stroke per one standard deviation lower bone mineral density after adjusting for multiple risk factors. In Cox proportional hazards models, risk of CHD death and risk of stroke death were not associated with low bone mineral density among men. For women, no significant associations were found for stroke (relative risk, 1.34; 95% confidence interval, 0.86-2.07, p = 0.20) or CHD (relative risk, 1.26; 95% confidence interval, 0.88, 1.80; p = 0.21). CONCLUSIONS: Low bone mineral density was not associated with risk of cardiovascular disease in men. Among women with low bone mineral density, risk of CHD and stroke were elevated, but no significant associations were found. PMID- 17728149 TI - Nonalcoholic fatty liver disease. AB - Nonalcoholic fatty liver disease (NAFLD) refers to the presence of hepatic steatosis not associated with a significant intake of ethanol. Insulin resistance is central to the pathogenesis of NAFLD; thus obesity, diabetes, and the metabolic syndrome are frequently associated with the disease. Consequently, as these metabolic conditions emerge as major health problems in Western society, it is now recognized that NAFLD is the most common chronic liver condition in the Western world. NAFLD is generally asymptomatic, although a minority of patients may present with evidence of progressive liver injury with complications of cirrhosis, liver failure, and hepatocellular carcinoma. Despite being common and potentially serious, relatively little is known about the natural history or prognostic significance of NAFLD. Although diabetes, obesity, and age are recognized risk factors for advanced liver disease, other significant factors leading to progressive liver injury remain to be identified. The treatment of NAFLD focuses upon modifying metabolic risk factors. Insulin-sensitizing and hepatoprotective drugs have been subjected to study trials, but as yet, no agent has conclusively been demonstrated to prevent disease progression. Management is further complicated by the inability to predict which patients will develop liver related morbidity and thus benefit from treatment. PMID- 17728150 TI - Electrochemical measurement of hydrogen peroxide in plasma: evaluation of freshwater prawn (Macrobrachium rosenbergii) and crucian carp (Cyprinus carpio) phagocytes under natural conditions. AB - An electrochemical technique for the real-time detection of hydrogen peroxide (H2O2) was employed to describe respiratory burst activity (RBA) of phagocytes in plasma which can be used to evaluate the ability of immune system and disease resistance. The method is based upon the electric current changes, by redox reaction on platinum electrode of extracellular hydrogen peroxide (H2O2) released from phagocytes stimulated by the zymosan at 680 mV direct current (d.c.). Compared with the control, activation of respiratory burst by zymosan particles results in a high amperometric response, and a current peak was obtained during the whole monitoring process. The peak current was proved by addition of Cu2+ and other controls, to be the result of intense release of H2O2 from phagocytes. The peak area was calculated and used to evaluate the quantity of effective H2O2, which represents the quantity of H2O2 beyond the clearance of related enzymes in plasma. According to Faraday's law, the phagocytes' ability of prawns to generate effective H2O2 was evaluated from 1.253 x 10(-14) mol/cell to 6.146 x 10(-14) mol/cell, and carp from 1.689 x 10(-15) mol/cell to 7.873 x 10(-15) mol/cell. This method is an acute and quick detection of extracellular effective H2O2 in plasma and reflects the capacity of phagocytes under natural conditions, which could be applied for selecting species and parents with high immunity for breeding in aquaculture. PMID- 17728151 TI - Reproducibility of kinematic motion coupling parameters during manual upper cervical axial rotation mobilization: a 3-dimensional in vitro study of the atlanto-axial joint. AB - INTRODUCTION: The reproducibility of the 3-dimensional (3D) kinematic aspects of motion coupling patterns of segmental manual mobilizing techniques is not yet known. This study analyzes the segmental 3D aspects of manual mobilization of the atlanto-axial joint in vitro. METHODS AND MATERIALS: Twenty fresh human cervical specimens were studied in a test-retest situation with two examiners. The specimens were manually mobilized using three different techniques: a regional mobilization technique, a segmental mobilization technique on the atlas with manual fixation of the axis and a segmental mobilization applying a locking technique. Segmental kinematics were registered with a Zebris CMS20 ultrasound based tracking system. The 3D aspects of motion coupling between main axial rotation and coupled lateral bending were analyzed by six parameters: the range of motion the three motion components, the cross-correlation, the ratio and the shift. RESULTS: The results indicate stronger intra- than inter-examiner reproducibility. The range of motion of the axial rotation component shows a substantial level of intra- and inter-examiner reproducibility (ICC's 0.67-0.76). The parameters describing the coupling patterns show only moderate to substantial intra-examiner reproducibility for the more experienced of the two examiners (ICC's 0.55-0.68). All other correlations were not significant and no differences could be observed between regional versus segmental techniques. CONCLUSION: Reproducibility of segmental 3D-aspects of manual mobilization of the atlanto axial joint in an in vitro situation can differ between examiners. The results of the present study may indicate a possible tendency to higher reproducibility if mobilizations are performed by an examiner with high expertise and experience in applying the specific techniques. Continued investigation including more examiners with different levels of experience and different techniques is necessary to confirm these observations. PMID- 17728152 TI - Embodiment, spatial categorisation and action. AB - Despite the subjective experience of a continuous and coherent external world, we will argue that the perception and categorisation of visual space is constrained by the spatial resolution of the sensory systems but also and above all, by the pre-reflective representations of the body in action. Recent empirical data in cognitive neurosciences will be presented that suggest that multidimensional categorisation of perceptual space depends on body representations at both an experiential and a functional level. Results will also be resumed that show that representations of the body in action are pre-reflective in nature as only some aspects of the pre-reflective states can be consciously experienced. Finally, a neuro-cognitive model based on the integration of afferent and efferent information will be described, which suggests that action simulation and associated predicted sensory consequences may represent the underlying principle that enables pre-reflective representations of the body for space categorisation and selection for action. PMID- 17728153 TI - Frequency-dependent activation pattern in the rat hippocampus, a simultaneous electrophysiological and fMRI study. AB - Frequency-dependent hippocampal activation during electrical perforant pathway stimulation was analyzed simultaneously by electrophysiological recordings in dentate gyrus and functional magnetic resonance imaging (fMRI). Pulse trains at low-frequency stimulation (2.5 Hz) did not influence electrophysiological responses within stimulation trains in the dentate gyrus and triggered no detectable BOLD responses. Increased stimulation frequencies (5.0-20 Hz) generated a roughly linear enhancement of the BOLD response. The BOLD signal within the dentate gyrus correlated more closely with stimulus pattern than with generated action potentials of the granular cells. However, the BOLD signal was strongly influenced by additional local signal processing activated by repetitive stimulus trains. fMRI visualized a frequency-specific spatial activation pattern of the hippocampus; spatially restricted activation in the dentate gyrus during 5 Hz stimulation, activation of the entire hippocampus and subiculum at 10 Hz and activation of the contralateral hippocampus during 20-Hz stimulation. PMID- 17728154 TI - Influence of chemosensory pain-expectancy on olfactory event-related potentials. AB - Health symptoms attributed to environmental odor exposure are not well understood. Cognitive factors seem to play a significant role in odor-related illness. In the present study, we investigated whether such influences are predominantly interpretational (i.e. best understood as interpretations of perceived odors), or also perceptual (i.e. affect perceptions of the characteristics of the odor). To investigate the neuronal activation behind such processes olfactory ERPs were recorded. The experiment consisted of two conditions: one where participants expected just several administrations of one odor (labelled as the "non-painful" condition), and one where they also expected, in between the odor administrations, to feel irritation in the nose (labelled as the "painful" condition). Participants received painless H(2)S stimuli during both conditions. To reinforce pain-expectancy, a CO(2) pulse was given occasionally during the "painful" condition. Crucial comparisons were made between reactions to H(2)S, under the two expectancy conditions. Detection sensitivity (reflected by amplitudes and latencies of the early N1 peak) and stimulus salience (reflected by amplitudes and latencies of the late "cognitive" positivity) were examined. Peak amplitudes were unaffected by expectancy condition. However, a significant main effect of expectancy on the N1 latency was found, which suggests that expecting a painful stimulus reduces the time to detect a harmless odor. In conclusion, expectancies seem to alter early aspects of odor perception. PMID- 17728155 TI - Phylogeny of the three brown banded land snail genus Humboldtiana (Pulmonata: Humboldtianidae). AB - The three brown banded land snail genus Humboldtiana (Pulmonata: Humboldtianidae) comprises 50 species of insular distribution from southern Texas to central Mexico; its low vagility and dispersal potential are reflected in high levels of endemism and highly restricted distributions. A current scheme of classification recognizes six subgenera: Polyomphala, Oreades, Gymnopallax, Clydonacme, Aglotrochus, and Humboldtiana (the latter containing three species groups). In the present work, mitochondrial 16S rDNA and partial ITS region and ribosomal large subunit (5.8S+ITS-2+28S) sequences from 26 recognized species and 2 populations of unknown identity were studied to assess phylogenetic relationships of Humboldtiana species using parsimony and Bayesian analysis, and AU test was used to compare the different phylogenetic hypotheses. The same four major clades were recovered by both methods (buffoniana, queretaroana, montezumae and fortis), although none of them support the current scheme of classification, with the only exception being the subgenus Gymnopallax included in the clade buffoniana. The results suggest that speciation patterns observed in the genus Humboldtiana could be explained as a morphostatic radiation. PMID- 17728156 TI - Phylogeny of the higher Libelluloidea (Anisoptera: Odonata): an exploration of the most speciose superfamily of dragonflies. AB - Although libelluloid dragonflies are diverse, numerous, and commonly observed and studied, their phylogenetic history is uncertain. Over 150 years of taxonomic study of Libelluloidea Rambur, 1842, beginning with Hagen (1840), [Rambur, M.P., 1842. Neuropteres. Histoire naturelle des Insectes, Paris, pp. 534; Hagen, H., 1840. Synonymia Libellularum Europaearum. Dissertation inaugularis quam consensu et auctoritate gratiosi medicorum ordinis in academia albertina ad summos in medicina et chirurgia honores.] and Selys (1850), [de Selys Longchamps, E., 1850. Revue des Odonates ou Libellules d'Europe [avec la collaboration de H.A. Hagen]. Muquardt, Bruxelles; Leipzig, 1-408.], has failed to produce a consensus about family and subfamily relationships. The present study provides a well substantiated phylogeny of the Libelluloidea generated from gene fragments of two independent genes, the 16S and 28S ribosomal RNA (rRNA), and using models that take into account non-independence of correlated rRNA sites. Ninety-three ingroup taxa and six outgroup taxa were amplified for the 28S fragment; 78 ingroup taxa and five outgroup taxa were amplified for the 16S fragment. Bayesian, likelihood and parsimony analyses of the combined data produce well-resolved phylogenetic hypotheses and several previously suggested monophyletic groups were supported by each analysis. Macromiinae, Corduliidae s. s., and Libellulidae are each monophyletic. The corduliid (s.l.) subfamilies Synthemistinae, Gomphomacromiinae, and Idionychinae form a monophyletic group, separate from the Corduliinae. Libellulidae comprises three previously accepted subfamilies (Urothemistinae, a very restricted Tetrathemistinae, and a modified Libellulinae) and five additional consistently recovered groups. None of the other previously proposed subfamilies are supported. Bayesian analyses run with an additional 71 sequences obtained from GenBank did not alter our conclusions. The evolution of adult and larval morphological characters is discussed here to suggest areas for future focus. This study shows the inherent problems in using poorly defined and sometimes inaccurately scored characters, basing groups on symplesiomorphies, and failure to recognize the widespread effects of character correlation and convergence, especially in aspects of wing venation. PMID- 17728157 TI - Functional and morphological changes in the dentate gyrus after experimental status epilepticus. AB - Status epilepticus may cause long-term functional and structural consequences possibly resulting in brain dysfunctions such as chronic epilepsy. In epileptogenesis, the dentate gyrus plays a key role in regulating the excitability of highly vulnerable and potentially epileptogenic downstream structures in the hippocampus proper. One, four and eight weeks after electrically induced status epilepticus, excitability and neuronal degeneration in the rat dentate gyrus were examined with intracerebral electrodes and Fluoro Jade (FJ) staining, respectively. Half of the animals had developed chronic epilepsy by 8 weeks after status epilepticus. Sham-operated controls did not exhibit seizures, and the excitatory parameters remained unchanged. Compared to controls, 8 weeks after status epilepticus the population spike latency in the dentate gyrus was significantly reduced (p<0.05) and substantial neuronal degeneration was seen (p<0.05). In summary, status epilepticus results in functional and morphological alterations in the dentate gyrus likely contributing to epileptogenesis. PMID- 17728158 TI - Socioeconomic and occupational risk factors for epilepsy: a nationwide epidemiological study in Sweden. AB - OBJECTIVES: The aim of this study is to investigate associations between hospitalization for epilepsy and two factors: socioeconomic status and occupation. DESIGN AND SETTING: A nationwide database was constructed in Sweden by linking the Swedish Census to the Hospital Discharge Register to obtain data on all first-time hospitalizations for epilepsy in adults in Sweden during the study period (1987-2004). Standardized incidence ratios (SIRs) were calculated by socioeconomic status and occupation. RESULTS: A total of 22,638 men and 16,871 women>30 years were hospitalized for epilepsy during the study period. Low education and low income (both men and women) and being an unskilled/skilled worker (only men) was associated with slightly but significantly increased risks. Among men, increased risk was noted for waiters, launderers and dry cleaners, clerical workers, other construction workers, sales agents and drivers. Among women, increased risk was observed among cooks and stewards and administrators and managers. CONCLUSIONS: Socioeconomic status and occupation sometimes carry significantly increased risks of hospital admission for epilepsy. PMID- 17728159 TI - Designing and delivering an epilepsy course for GPs to help meet their educational needs. AB - BACKGROUND: With the recent publication of comprehensive evidence based guidelines and the inclusion of epilepsy in the new GMS contract in the UK the importance of epilepsy to primary care has become clear. There seem to be many deficiencies in GP service provision for epilepsy including a lack of structured review and poor information provision for patients. Therefore, it is likely that further education on epilepsy management is essential. AIM: To ascertain what GPs wish to learn about epilepsy and their preferences as to which methods should be used to achieve this. To use this information to design and then deliver an epilepsy teaching programme for GPs. DESIGN OF STUDY: Cross-sectional. SETTING: Primary care, Lothian region, Scotland. METHODS: A questionnaire was designed and delivered to 50 GPs to obtain information related to the aims of the study. These results were used to aid the design of an epilepsy teaching day for GPs. This course was then delivered in West Lothian, Scotland. RESULTS: GPs seemed to prefer weekday, half-day teaching using multidisciplinary lectures and case studies. Drug treatment, referral guidelines and diagnosis were considered the most important topics and the teaching programme received mainly positive feedback from participants. CONCLUSION: It would appear that a short course on epilepsy management, when designed with the preferences of participating GPs in mind, can be readily delivered and well received. PMID- 17728161 TI - Optical techniques for imaging membrane lipid microdomains in living cells. AB - Lateral organisation of cellular membranes, particularly the plasma membrane, is of benefit to the cell as it allows complicated cellular processes to be regulated and efficient. For example, trafficking and secretion of molecules can be targeted and directed, cells polarised and signalling events modulated and propagated. The fluid mosaic model allows for significant heterogeneity on the part of the lipids themselves and of membrane associated proteins. By exploiting the tendency of complex lipid bilayers to undergo spontaneous or induced phase separation into non-miscible domains, the cell could achieve this desired spatial organisation. While phase-separation is readily observed in simple, artificial bilayers, its occurrence in physiological membranes remains controversial. This stems mainly from our inability to image lipid microdomains directly - possibly due to their small size, short lifespan and/or morphological similarity to the bulk membrane. In this review, we seek to examine the techniques used to try to image membrane lipid microdomains, concentrating mainly on optical microscopy techniques that are applicable to live cells. We also look at novel emerging instruments and methods that promise to overcome our current technological limitations and shed new light on these important structures. PMID- 17728162 TI - Pathology of naturally occurring bovine tuberculosis in England and Wales. AB - The aim of this study was to obtain a contemporary data set of pathology in tuberculin reactor and in-contact cattle in England and Wales. Four hundred animals (200 reactors and 200 in-contacts) from 242 farms located in 14 counties in Western England and Wales were examined. The mean number of lymph nodes (LNs) with tuberculosis (TB)-like lesions per TB-confirmed animal was 1.7 in reactors and 1.5 in in-contact animals. Tuberculous lesions in both reactor and in-contact animals were most commonly observed in the LNs of the thorax, followed by the head and abdomen, particularly the mediastinal, retropharyngeal and tracheobronchial LNs. Twenty-five reactors had macroscopic lesions in the palatine tonsils. Among TB-confirmed cattle, 27% of reactors and 9% of in-contact animals had gross TB-like lesions in the lungs, particularly in the caudal lobes. Gross lesions that were not TB-confirmed were parasitic granulomas (45%), bacterial or mycotic club-forming pyogranulomas (27%) and bacterial abscesses (23%). Diagnostic sensitivity was maximised when bacteriology and histopathology were used concurrently. Stage IV granulomas, alone or in combination with other stages, constituted 63% of lesions, while 16% of lesions were stage I/II granulomas. Caseous necrosis and calcification were common features of the granulomas encountered in natural Mycobacterium bovis infections, even with pathology limited to a small number of sites. Granulomas often covered large areas of histological sections and typically contained only small numbers of acid fast bacilli. PMID- 17728160 TI - Hippocampal infusions of glucose reverse memory deficits produced by co-infusions of a GABA receptor agonist. AB - Although septal infusions of glucose typically have positive effects on memory, we have shown repeatedly that this treatment exacerbates memory deficits produced by co-infusions of gamma-aminobutyric acid (GABA) receptor agonists. The present experiments tested whether this negative interaction between glucose and GABA in the medial septum would be observed in the hippocampus, a brain region where glucose typically has positive effects on memory. Specifically, we determined whether hippocampal infusions of glucose would reverse or exacerbate memory deficits produced by hippocampal co-infusions of the GABA receptor agonist muscimol. Fifteen minutes prior to either assessing spontaneous alternation (SA) or continuous multiple trial inhibitory avoidance (CMIA) training, male Sprague Dawley-derived rats were given bilateral hippocampal infusions of vehicle (phosphate-buffered saline [PBS], 1 microl/2 min), glucose (33 or 50 nmol), muscimol (0.3 or 0.4 microg, SA or 3 microg, CMIA) or muscimol and glucose combined in one solution. The results indicated that hippocampal infusions of muscimol alone decreased SA scores and CMIA retention latencies. More importantly, hippocampal infusions of glucose, at doses that had no effect when infused alone, attenuated (33 nmol) or reversed (50 nmol) the muscimol-induced memory deficits. Thus, although co-infusions of glucose with muscimol into the medial septum impair memory, the present findings show that an opposite effect is observed in the hippocampus. Collectively, these findings suggest that the memory impairing interaction between glucose and GABA in the medial septum is not a general property of the brain, but rather is brain region-dependent. PMID- 17728163 TI - Genetic differentiation of the nucleocapsid protein of Korean isolates of porcine epidemic diarrhoea virus by RT-PCR based restriction fragment length polymorphism analysis. AB - A reverse transcriptase polymerase chain reaction (RT-PCR) based restriction fragment length polymorphism (RFLP) analysis based on the nucleocapsid (N) gene was developed to differentiate between field isolates of porcine epidemic diarrhoea virus (PEDV) and a vaccine strain, J-vac. Thirteen field isolates of PEDV from Korea were distinguishable from the vaccine strain and the prototype PEDV strain CV777 by RFLP using Tru9I. RFLP patterns in 11 of 13 field PEDV isolates were different from the vaccine strain using AspLEI, HgaI and MspR9I. Sequence analysis of the PEDV N gene revealed that Korean field PEDV isolates had 93.6% and 89.6% identity with the vaccine virus at nucleotide and amino acid sequence levels, respectively, suggesting progressive point mutations of the PEDV genome in the field. RFLP analysis of the PEDV N gene is a promising tool for distinguishing field strains from the vaccine-derived virus. PMID- 17728164 TI - Culicoides species attracted to horses with and without insect hypersensitivity. AB - The aims of this study were to determine (1) which species of Culicoides is most commonly attracted to horses, (2) whether horses suffering insect hypersensitivity attract more Culicoides spp. than unaffected horses, and (3) the times when Culicoides spp. are most active. Horses affected by insect hypersensitivity and unaffected horses were placed inside mosquito netting tents for 30 min at different times of the day. All Culicoides spp. trapped inside the tents were collected and identified. C. obsoletus was the most common species found, followed by C. pulicaris. Healthy horses attracted slightly more midges than horses that were affected with insect hypersensitivity. All of the Culicoides species were most active at sunset, less so at sunrise and very few or no midges were trapped in the afternoon or at night. PMID- 17728166 TI - Polymorphism of transferrin of carp seminal plasma: relationship to blood transferrin and sperm motility characteristics. AB - Transferrin (Tf) is a major protein of carp (Cyprinus carpio) seminal plasma. Its relationship with milt quality is unknown. In this study, we sought to determine if Tf is polymorphic in carp seminal plasma and if this polymorphism is related to sperm motility characteristics. We screened males of purebred common carp line (Polish line R6) for Tf polymorphism in blood plasma. The majority of Tf genotypes represented only DD and DG variants. We then collected milt from preselected DD and DG genotypes and tested their sperm motility characteristics using computer-aided sperm analysis (CASA). Tf polymorphism in seminal plasma was found to be identical with that of blood. However, the relationships between Tf polymorphism and iron metabolic parameters were different for blood and semen. These data suggest different regulation of Tf in liver and testis. We found substantial differences in sperm motility characteristics between both genotypes. Spermatozoa of DG males were characterized by lower curvilinear velocity (VCL), amplitude of lateral head displacement (ALH), higher linearity (LIN) and straightness (STR) of movement as compared to DD males. No differences were found in other sperm characteristics such as sperm concentration and percentage of sperm motility. Our results suggest that sperm motility parameters are related to Tf polymorphism and therefore this polymorphism may be related to sperm competitive ability. PMID- 17728165 TI - Prediction of the 3-D structure of rat MrgA G protein-coupled receptor and identification of its binding site. AB - Mrg receptors are orphan G protein-coupled receptors (GPCRs) located mainly at the specific set of sensory neurons in the dorsal root ganglia, suggesting a role in nociception. We report here the 3-D structure of rat MrgA (rMrgA) receptor [obtained from homology modeling to the recently validated predicted structures of mouse MrgA1 and MrgC11] and the structure of adenine (a known agonist, K(i)=18nM) bound to rMrgA. This predicted binding site is located within transmembrane helical domains (TMs) 3, 4, 5 and 6, with Asn residues in TM3 and TM4 identified as the key residues for adenine binding. Here the side chain of Asn88 (TM3) forms two pairs of hydrogen bonds with N3 and N9 of adenine while Asn146 (TM4) makes two pairs of hydrogen bonds with N1 and N6 of adenine. These interactions lock adenine tightly in the binding pocket. We also predict the binding site of guanine (not an agonist) and seven other derivatives. Guanine cannot make the hydrogen bond to Asn146 (TM4), leading to binding too weak to be observed experimentally. The predicted binding affinity for other adenine derivatives correlates with the availability of the hydrogen bonds to these two Asn residues. These results validate the predicted structure for rat MrgA and suggest mutation experiments that could further validate the structure. Moreover, the predicted structure and binding site should be useful for seeking other small molecule agonists and antagonists. PMID- 17728168 TI - A review of the role of enhanced apoptosis in the pathophysiology of cystinosis. AB - The role of lysosomal cystine in development of the phenotype in cystinosis is problematic, in that the cystine is effectively isolated from the rest of cellular metabolism. Several models have been proposed, but most do not provide a mechanism for such an interaction. During early apoptosis the lysosomes are permeablized, providing such access. We have shown that lysosomal cystine enhances apoptosis in cultured normal and cystinotic fibroblasts and cultured renal proximal tubule epithelial cells, that the process occurs via mixed disulfide (cysteinylation) formation, and that PKC delta is involved. Further, the "swan neck" deformity of proximal renal tubules, long a hallmark of cystinosis, is explicable via this model, as is the renal failure that results from progression of tubule cell loss to atubular glomeruli. Modification of this process by other genes may explain the milder forms of the disease. PMID- 17728167 TI - A novel growth hormone receptor gene deletion mutation in a patient with primary growth hormone insensitivity syndrome (Laron syndrome). AB - OBJECTIVE: Growth hormone (GH) insensitivity syndrome (Laron syndrome) is known to be caused by genetic disorders of the GH-IGF-1 axis. Although many mutations in the GH receptor have been identified, there have been only a few reports of deletions of the GH receptor gene. DESIGN: A Japanese adult female patient with Laron syndrome was subjected to chromosome analysis with basic G-banding and also with a high accuracy technique. Each exon of the GH receptor gene was amplified by means of PCR. Since this patient was diagnosed with osteoporosis, the effects of alendronate on bone mineral density (BMD) were also examined. RESULTS: The chromosome analysis with the high accuracy technique demonstrated a large deletion of the short arm in one allele of chromosome 5 from p11 to p13.1 [46, XX, del (5) (p11-p13.1)]. PCR amplification of exons of the GH receptor gene showed that only exons 2 and 3 were amplified. Low-dose IGF-1 administration (30microg/kg body weight) failed to increase her BMD, whereas alendronate administration resulted in an increase associated with a decrease in urinary deoxypyridinoline (DPD) and serum osteocalcin concentrations. CONCLUSIONS: The GH receptor gene of the patient was shown to lack exons 4-10. To the best of our knowledge, this is the third case report of Laron syndrome with large GH receptor deletion. Alendronate was effective for the enhancement of BMD. PMID- 17728169 TI - Broncholithiasis in a cat: clinical findings, long-term evolution and histopathological features. AB - A 14-year-old neutered male Persian cat was evaluated because of an acute exacerbation of a chronic cough of 2-3 years of duration. Physical examination was normal except for the auscultation of accentuated breath sounds and wheezes cranially on both sides of the chest. Complete blood count, biochemical parameters and urinalysis were normal. Thoracic radiographs showed a generalised nodular pattern with multiple mineral opacities. Oral prednisone and doxycycline were prescribed. Two weeks later, the frequency of the cough was significantly reduced. Terbutaline was recommended for relief of acute exacerbations. Three years later the cat was evaluated again due to a non-related disease that led to the euthanasia of the cat. Concerning its respiratory disease, the cat had experienced nearly asymptomatic periods of 3-6 weeks of duration punctuated by acute exacerbation periods of 7-10 days, during which terbutaline was useful to relieve the cough. Thoracic radiographs showed a mild increase in the size and extent of the pulmonary mineralisation. Histopathologically, mild bronchitis and bronchiectasis were evident, accompanied by calcified bronchial plugs and marked hyperplasia and hypertrophy of the seromucinous glands. Based on clinical and pathoanatomical findings, a final diagnosis of miliary broncholithiasis and bronchiectasis was made. Broncholithiasis should be considered in differential diagnosis of pulmonary mineralisation in cats. When no concomitant diseases are present, this rare disease appears to have a slowly progressive evolution that does not appear to carry a bad prognosis and may be satisfactorily managed with combinations of bronchodilators and corticosteroids. PMID- 17728170 TI - [Patient's information: a full medical act that demands evaluation]. PMID- 17728171 TI - [Should the age of the male be a limiting factor in the assisted reproductive process of a couple? Gynecol Obstet Fertil 2007;35:495-7]. PMID- 17728172 TI - [Assisted reproductive techniques (ART): the point of view of patients and their organizations]. AB - Assisted reproductive technology (ART) for couples affected by HIV constitutes an important progress for public health. France has been the first country to offer this possibility on a national level, within the public health care system, with the best security and quality standards. This progress is, for one part, a consequence of the collaboration between community-based organizations representing HIV positive persons and their close relations, and pioneer medical teams in this field. This collaboration and this alliance have led to progressively convince the medical community and public health authorities concerned by the fight against aids of the usefulness of this care. Nevertheless, different obstacles have been encountered on the way between theory (decision of the Minister of Health, May 2001, allowing ART for couples affected by HIV), and practice. Medical teams often lack staff in sufficient number. Some doctors have, for reasons they qualify as ethical, refused to take HIV positive women into care. The opening of medical centers in areas where they are missing, particularly the French territories of America, remains a high priority. Last, the legal limits restricting access to ART in France deserve to be questioned. Community-based organizations and medical teams have been able to work as partners, sharing common goals of public health and quality of care. Nevertheless, among health institutions and national agencies in France, the consideration of the point of view of patients and their organizations is far from being a general rule, despite laws which clearly define patients' collective rights. We thank the Federation francaise d'etude de la reproduction (FFER) and the journal Gynecologie Obstetrique & Fertilite for giving non-governmental organizations an opportunity to reaffirm our commitment to constructive common work. PMID- 17728174 TI - Trypanosoma cruzi infection from the view of CD8+ T cell immunity--an infection model for developing T cell vaccine. AB - Chagas' disease is caused by Trypanosoma cruzi (T. cruzi) which was once prevalent in Central and South America. Although the recent success in Triatoma vector control has made the disease being possibly "extinct" in the near future, the development of effective preventive and therapeutic vaccines is still necessary to prevent the resurgence of the neglected infection. In addition to the importance for containing the disease, T. cruzi infection presents unique features for elucidating hosts' immune responses against intracellular infectious agents. Due to its biological capacity for invading into principally any types of cells and for causing systemic infection which damages particularly muscle and neural cells, T cell immunity is critical for resolving its infection. Although T cell-mediated immune responses have been, so far, extensively investigated in viral and bacterial infections, parasitic infection such as malaria has presented epoch-making discovery in T cell immunity. Recent advances in the analyses of T cell-mediated immune responses against T. cruzi infection now make this infectious disease potentially more suitable for detecting subtle immunological changes in hosts' immune defense upon modifying immune system. The current review focuses on the usefulness of T. cruzi infection as a model for developing effective CD8(+) T cell-mediated vaccine against intracellular infectious agents. PMID- 17728175 TI - Vibrational spectrum and assignments of 2-(4-methoxyphenyl)-1H-benzo[d]imidazole by ab initio Hartree-Fock and density functional methods. AB - The room temperature attenuated total reflection Fourier transform infrared spectrum of the 2-(4-methoxyphenyl)-1H-benzo[d]imidazole has been recorded with diamond/ZnSe prism. The conformational behaviour, structural stability of optimized geometry, frequency and intensity of the vibrational bands of the title compound were investigated by utilizing ab initio calculations with 6-311G** basis set at HF, B3LYP, BLYP, B3PW91 and mPW1PW91 levels. The harmonic vibrational frequencies were calculated and scaled values have been compared with experimental IR spectrum. The observed and the calculated frequencies are found to be in good agreement. The theoretical vibrational spectra of the title compound were interpreted by means of potential energy distributions using VEDA 4 program. Furthermore, the optimal uniform scaling factors calculated for the title compound are 0.9120, 0.9596, 0.9660, 0.9699, and 0.9993 for HF, mPW1PW91, B3PW91, B3LYP and BLYP methods, respectively. PMID- 17728176 TI - Laser Raman spectroscopy of THF clathrate hydrate in the temperature range 90-300 K. AB - In situ Raman and Fourier transform infrared (FTIR-NIR) spectroscopic studies on tetrahydrofuran (THF-C(4)H(8)O) clathrate hydrate (CH) were reported. The Raman results in lattice (64 cm(-1)), ring breathing and C-H stretching mode regions are in conformity with earlier reports, while the FTIR (NIR) studies in second order mode region were reported for the first time. Comparison of the results indicate that the band assigned to ring breathing mode around 922 cm(-1) (in Raman) and corresponding second order mode in NIR around 4295 cm(-1) broadens and shifts in enclathrated THF. The ring breathing mode at lower temperatures (T<120 K) is highly asymmetric and splits into two and are due to different host-guest interactions at lower temperatures. PMID- 17728177 TI - Photovoltaic response and values of state dipole moments in single-layered pyrazoloquinoline/polymer composites. AB - We report the photovoltaic response of composite films formed by polymer transport matrices poly(3-octylthiophene) (P3OT) and poly(3-decylthiophene) (PDT) with incorporated 1H-pyrazolo[3,4-b]quinoline (PAQ) chromophore (see the first figure). The photovoltage (PV) data were obtained for different substituted PAQ possessing different state dipole moments. The photovoltaic cells were formed between ITO and aluminum electrodes. We found that the PV signal of polymer/PAQ substantially depends on the state dipole moments of the pyrazoloquinoline chromophore. This fact indicates on a possibility of significant enhancement of PV efficiency by appropriate variations of the state dipole moments of chromophore. This results in photoinduced electron transfer from polymer serving as donors to PAQ being the electron acceptor. Despite an efficiency of the PV devices is below 1%, however, it may be substantially enhanced in future varying the chromophore state dipole moments appropriately. PMID- 17728178 TI - Transition metal complexes of isonicotinic acid (2-hydroxybenzylidene)hydrazide. AB - A new series of transition metal complexes of Schiff base isonicotinic acid (2 hydroxybenzylidene)hydrazide, HL, have been synthesized. The Schiff base reacted with Cu(II), Ni(II), Co(II), Mn(II), Fe(III) and UO2(II) ions as monobasic tridentate ligand to yield mononuclear complexes of 1:2 (metal:ligand) except that of Cu(II) which form complex of 1:1 (metal:ligand). The ligand and its metal complexes were characterized by elemental analyses, IR, UV-vis, mass and 1H NMR spectra, as well as magnetic moment, conductance measurements, and thermal analyses. All complexes have octahedral configurations except Cu(II) complex which has an extra square planar geometry distorted towards tetrahedral. While, the UO2(II) complex has its favour hepta-coordination. The ligand and its metal complexes were tested against one strain Gram +ve bacteria (Staphylococcus aureus), Gram -ve bacteria (Escherichia coli), and Fungi (Candida albicans). The tested compounds exhibited higher antibacterial activities. PMID- 17728179 TI - Detection and differentiation of wild-type and vaccine mutant varicella-zoster viruses using an Invader Plus method. AB - We report the use of a prototype Invader Plus method (Third Wave Technologies, Inc., Madison, WI) for the qualitative detection of varicella-zoster virus (VZV) and differentiation of wild-type and Oka vaccine VZV. The analytical sensitivity of the VZV Invader Plus reagents is at 10 copies per reaction. A total of 174 skin and mucous swab specimens were used to validate the assay's performance. The sensitivity and specificity were 98.3% and 98.1%, respectively, in comparison to a PCR-EIA assay. A perfect 100% agreement was obtained when VZV wild-type and vaccine differentiation was performed on 54 VZV-positive swab specimens against an allele-specific FRET real-time assay. The Invader Plus method provides another reliable tool for qualitative detection of VZV and differentiation of wild-type and vaccine virus. PMID- 17728180 TI - Induction of choline kinase alpha by carbon tetrachloride (CCl4) occurs via increased binding of c-jun to an AP-1 element. AB - The mechanism by which treatment of mice with CCl4 induces an increase in choline kinase alpha has been investigated. Nuclear run on assays demonstrated a major increase in the transcript for choline kinase alpha in livers from mice 3 h and 6 h after administration of CCl4 compared to vehicle (olive oil). 5'deletion analyses of choline kinase alpha promoter-luciferase constructs expressed in Hepa 1 cells identified a promoter element between -875 and -866 that was nearly identical to an AP-1 consensus site. Mutation of this AP-1 site caused a striking decrease in the expression of choline kinase alpha promoter-luciferase constructs. Electromobility shift assays with nuclear extracts from mouse liver demonstrated that c-Jun, but not c-fos, bound oligonucleotides with the AP-1 site. The amount of c-jun bound was greatly increased when hepatic nuclear extracts from mice treated with CCl4 were used. Chromatin immunoprecipitation assays confirmed that c-jun binds to the choline kinase alpha promoter. The results from these studies provide strong evidence that the choline kinase alpha promoter has a distal element (-875/-867) that binds c-jun and the binding of c jun is enhanced by treatment with CCl4. PMID- 17728181 TI - Reverse ventricular remodelling after cardiac resynchronization therapy is associated with a reduction in serum tenascin-C and plasma matrix metalloproteinase-9 levels. AB - BACKGROUND: In heart failure patients, cardiac resynchronization therapy (CRT) leads to reverse ventricular remodelling. AIM: The aim of this study was to evaluate whether changes in levels of circulating biomarkers of extracellular matrix metabolism correlate with the response to CRT. METHODS AND RESULTS: Clinical parameters, left ventricular (LV) volumes, and circulating levels of tenascin-C (TNC), matrix metalloproteinase-2 (MMP-2), MMP-9, and amino-terminal propeptide of brain natriuretic peptide (NT-proBNP) were assessed in 64 patients at baseline and 6 months follow-up. The majority of patients (72%) showed a >10% reduction in LV end-systolic volume at follow-up, and were classified as responders to CRT. The remaining patients were classified as non-responders. In responders, a significant decrease in circulating levels of TNC (from 60+/-40 ng/mL to 47+/-30 ng/mL, p<0.01), MMP-9 (from 55+/-30 AU to 44+/-27 AU, p<0.01), and NT-proBNP (from 2106+/-1805 pg/mL to 1132+/-1289 pg/mL, p<0.001) were observed at follow-up; MMP-2 levels were unchanged. In non-responders TNC, NT proBNP, MMP-9 and MMP-2 levels remained unchanged. CONCLUSION: At 6 months follow up, CRT was associated with reverse LV remodelling, and a significant decrease in TNC, MMP-9, and NT-proBNP levels. This suggests an important role of ECM modulation in the process of reverse ventricular remodelling in patients responding to CRT. PMID- 17728182 TI - Sleep in children with autistic spectrum disorder: a questionnaire and polysomnographic study. AB - OBJECTIVE: To evaluate sleep in children with autistic spectrum disorder (ASD) by means of sleep questionnaires and polysomnography; moreover, to analyze their cyclic alternating pattern (CAP). METHODS: Thirty-one patients with ASD (28 males, 3 females, aged 3.7-19 years) and age-matched normal controls were included. ASD children were evaluated by a standard sleep questionnaire that consisted of 45 items in a Likert-type scale covering several areas of sleep disorders and by overnight polysomnography in the sleep laboratory after one adaptation night. RESULTS: The questionnaire results showed that parents of ASD children reported a high prevalence of disorders of initiating and maintaining sleep, enuresis, repetitive behavior when falling asleep, and daytime sleepiness. Polysomnographically, ASD children showed reduced time in bed, total sleep time, sleep period time and rapid eye movement (REM) latency. ASD subjects had a CAP rate during slow-wave sleep (SWS) lower than normal controls, together with a lower percentage of A1 subtypes. CONCLUSIONS: ASD children questionnaires showed a higher percentage of disorders of initiating and maintaining sleep than normal controls; this was not completely confirmed by sleep staging. CAP measures showed subtle alterations of NREM sleep which could be detected with an appropriate methodology of analysis. The reduction of A1 subtypes during SWS might play a role in the impairment of cognitive functioning in these subjects. PMID- 17728183 TI - Environmental tobacco smoke exposure in children in two districts of the Czech Republic. AB - In the course of epidemiologic studies on the health of preschool children in the Teplice and Prachatice districts of the Czech Republic, we have recorded the frequency of smokers in the families of the children under study and the exposure of the children to environmental tobacco smoke (ETS) by assaying urinary cotinine levels. Questionnaires were administered at the age of 3 years (children born 1994-1996) or 4.5 years (children born 1997-1998). Out of 1128 respondents, 35.6% of the mothers and 48.9% of their husbands/partners were smokers. Taking into account other adult smokers, 41.6% of children lived in households without smokers and 30.1% in households with one smoker. There were more smokers among both mothers and fathers in Teplice than in the Prachatice district (mothers: 41.1% vs. 28.5%, P=0.017; fathers: 50.8% vs. 46.5%, NS). Cotinine concentration in the urine was determined using a radioimmunoassay in 523 pairs of mothers and children at the age of 4.5 years. A level higher than 500 ng cotinine per mg creatinine (our cut-off for active smoking) was detected in 199 out of 523 mothers (38%). Using 20 ng/mg as the cut-off, 48.2% of 523 children were exposed to ETS. There were more ETS-exposed children in Teplice than in the Prachatice district (59.2% vs. 34.7%, P<0.001). When cotinine levels were measured in 479 of these children at the age of 6-7 years, the percentage of children exposed to ETS decreased to 36.5%. However, the difference between Teplice and Prachatice children persisted (44.6% vs. 27.8%). Our results suggest that in the Czech Republic, children under 5 years of age are significantly exposed to tobacco smoke and that more effective regulatory measures are needed to decrease the prevalence of smoking. PMID- 17728184 TI - Microbiological quality of indoor and outdoor swimming pools in Greece: investigation of the antibiotic resistance of the bacterial isolates. AB - During 1997-2005, the microbiological quality and susceptibility of bacterial isolates of swimming pool waters were investigated. A total of 462 water samples were collected from three indoor swimming pools (a teaching pool, a competition public pool, a hydrotherapy pool) and two outdoor swimming pools (a hotel semi public and a residential private pool) in Northwestern Greece. All water samples were analyzed for the presence of bacteria, protozoa and fungi and susceptibility tests were performed for the bacterial isolates. Sixty-seven percent of the examined water samples conformed to the microbiological standards and 32.9% exceeded at least one of the indicated limits. Out of 107 bacterial isolates, 38 (35.5%) resistant strains were detected. Multi-resistant Pseudomonas alcaligenes, Leuconostoc, and Staphylococcus aureus (isolated from the teaching pool), Staphylococcus wernerii, Chryseobacterium indologenes and Ochrobactrum anthropi (isolated from the competition pool), Pseudomonas aeruginosa, P. fluorescens, Aeromonas hydrophila, Enterobacter cloacae, Klebsiella pneumoniae and S. aureus (isolated from the hydrotherapy pool) and A. hydrophila (isolated from the hotel pool) were detected. The swimming pool with the poorest microbiological quality (THC 500 cfu/ml in 12.1% of the samples, P. aeruginosa counts 1500 cfu/100 ml in 6% of the samples) and the highest prevalence of multi-resistant isolates (73.6%) was the hydrotherapy pool. No Cryptosporidium or Giardia cysts and no Legionella, Mycobacteria and Salmonella were detected, but there were isolations of Candida albicans, Aspergillus spp., Mucor spp., Alternaria spp., Rhizopus spp., Trichophyton spp., and Penicillium spp. PMID- 17728185 TI - Very late stent fracture associated with a sirolimus-eluting stent. AB - Late stent thrombosis (>1 year after implantation) is a recognised complication involving drug-eluting stents. Stent fracture is increasingly being reported as a complication of drug-eluting stent, and in particular sirolimus-eluting stent use. We report the case of very late sirolimus-eluting stent fracture resulting in an acute coronary syndrome. This case report highlights the need for greater awareness and post-marketing surveillance to detect a potential mechanism for late stent thrombosis in the drug-eluting stent era. PMID- 17728186 TI - Development of a clinical evaluation tool for baccalaureate nursing students. AB - The purpose of clinical evaluation is to facilitate the development of students into safe, ethical and accountable practitioners. Evaluation measures should ensure fairness, consistency across settings and teachers, utilize indicators which reflect the realities of practice and education and facilitate deeper level student/teacher clinical discourse and learning. A new clinical evaluation tool was developed in a baccalaureate program in Ontario to address the variety of tools utilized and the need to demonstrate progression in depth and scope of practice. A consistent evaluation process was needed, leveled over the four years of the program and framed by the School's five program outcomes: knowledge worker, critical thinker, self-directed learner, evolving professional and effective communicator. A new tool was borne through an examination of relevant literature, the five program outcomes, College of Nurses of Ontario entry to practice competencies, practicum course outlines and various tools used in the undergraduate program. The process of tool development involved multiple drafts, ongoing dialogue and meetings with clinical teachers and course coordinators as well as feedback from students. Commitment, collaboration and collegiality were key elements in the construction of this tool. PMID- 17728188 TI - Discharges in ventromedial frontal cortex during absence spells. AB - Neural mechanisms of conscious attention require thalamic control of widespread cortical networks. Absence spells involve a momentary loss of voluntary control of attention, during which the person is inactive and unresponsive. The spike wave seizure discharges of these spells rapidly engage both cerebral hemispheres in the classic sign of a "generalized" seizure. Animal evidence suggests that spike-wave seizures are caused by a disruption of thalamic circuitry, with extensive spread to cortex through thalamocortical propagation. We applied advanced methods of electrical source analysis to dense array (256-channel) electroencephalographic recordings of spike-wave discharges of absence spells. Neither the onset nor the spread of these seizures is generalized. Rather, the slow waves of the discharges are restricted to frontotemporal networks, and the spikes represent a highly localized and stereotyped progression of electrophysiological activity in ventromedial frontal networks. Given the current knowledge of the neurophysiology of absence seizures, this specificity of the frontal cortical discharges suggests the hypothesis that absence spells are associated with pathology in a circuit comprising ventromedial frontal cortex, rostral thalamic reticular nucleus, and limbic nuclei of the thalamus. Disrupted in absence, this circuit appears to regulate important aspects of the voluntary control of conscious attention. PMID- 17728187 TI - CpG oligodeoxynucleotides induce cyclooxygenase-2 in human B lymphocytes: implications for adjuvant activity and antibody production. AB - Synthetic CpG oligodeoxynucleotides (ODN), similar to DNA sequences found in certain microorganisms, have shown promise as adjuvants for humans by enhancing immune responses. Since antibodies are often indicators of successful vaccination, it is important to understand how CpG ODNs affect human B cells and influence antibody production. Treatment of human B cells with synthetic CpG ODN sequences increased both steady-state Cox-2 mRNA levels and protein expression. B cell receptor stimulation in concert with CpG ODN treatment induced Cox-2 expression and production of prostaglandin E(2), well above that seen with CpG ODN alone. Importantly, CpG-induced human B cell IgM and IgG production was attenuated by dual Cox-1/Cox-2 inhibitors and Cox-2-selective inhibitors. Our findings support a key role for CpG ODN-induced human B cell Cox-2 in the production of IgM and IgG antibodies, revealing that drugs that attenuate Cox-2 activity have the potential to reduce optimal antibody response to adjuvants/vaccination. PMID- 17728189 TI - Biochemical biomarkers in chronically metal-stressed daphnids. AB - Biochemical biomarkers are a popular measure of toxic effects on organisms due to their assumed fast response, and are usually assessed after acute exposure of the organism to the stressor. However, increasing interest in the use of biochemical biomarkers in environmental pollution monitoring calls for more laboratory long term studies of contaminants' effects on biochemical endpoints. In this study, four biochemical biomarkers (protein content, activity of cholinesterase (ChE), catalase (CAT) and glutathione S-transferase (GST), were correlated with standardised reproductive and survival endpoints of water fleas (Daphnia magna) after chronic exposure to Cr (VI) and Cd. No effect on the reproduction and survival was noticed up to the highest tested concentration of Cr (VI) (52.5 microg/L), while the protein content, and the ChE and CAT activity decreased, and GST activity increased. Cd affected reproduction of daphnids above 0.656 microg/L, but the protein content and ChE activity were changed at 0.328 microg/L and 0.082 microg/L of Cd, respectively. Biochemical biomarkers in some cases proved to be equally or more sensitive than reproduction and mortality. We recommend more frequent use of a battery of biochemical biomarkers in combination with other higher-level biomarkers also in chronic studies and not only in the acute ones. PMID- 17728190 TI - Antioxidant defenses and biochemical changes in pacu (Piaractus mesopotamicus) in response to single and combined copper and hypoxia exposure. AB - The effect of combined-factors (hypoxia+copper) on the biochemical parameters and antioxidant defenses were studied in the neotropical fish Piaractus mesopotamicus. Fish were exposed for 48 h to 0.4 mg Cu(2+) L(-1) (0.4Cu), hypoxia=50 mm Hg (Hpx), and 0.4 mg Cu(2) L(-1)+hypoxia=50 mm Hg (0.4CuHpx). The exposure to 0.4Cu increased the reactive oxygen species (ROS) in the liver, accompanied by increases in superoxide dismutase (SOD) and decreases in catalase (CAT) activity, showing the influence of copper in this protection. The exposure to Hpx decreased the activity of glutathione peroxidase (GSH-Px) and CAT. Exposure to a combined-factor caused an increase in the ROS production followed by an increase in SOD and a decrease in GSH-Px and CAT. At 0.4Cu, fish presented a reduction in CAT, while in Hpx decreases in SOD, CAT and GSH-Px were observed in red muscles. Single-factors were insufficient to cause ROS production. In combined-factors, increased ROS formation and decreased SOD, CAT and GSH-Px were observed. RBC increased in all groups, but only under combined-factors was there an increase in hemoglobin. Copper plasma concentration increased in groups exposed to copper. Na(+)/K(+)-ATPase activity in gills decreased in 0.4Cu and 0.4CuHpx, and increased in Hpx. Metallothionein concentration in gills increased under combined-factors. Combined-factors caused significant disturbances in the antioxidant defenses and biochemical parameters than single-factors. PMID- 17728191 TI - Pharmacological preconditioning by levosimendan is mediated by inducible nitric oxide synthase and mitochondrial KATP channel activation in the in vivo anesthetized rabbit heart model. AB - BACKGROUND: Provocation of fatal cardiac arrhythmias has limited the use of inotropic agents as heart failure therapy. Levosimendan (LEV) is a new inodilator, whose mechanism of action includes calcium sensitization of contractile proteins and the opening of ATP-dependent potassium channels. OBJECTIVES AND METHODS: The aim of this investigation was to test whether the administration of LEV has cardioprotective and antiarrhythmic effects against ischemia and reperfusion injury in a manner similar to ischemic preconditioning (IPC) in a well-standardized model of reperfusion arrhythmias in anesthetized adult male rabbits (n=122) subjected to 30 min occlusion of the left coronary artery followed by 120 min of reperfusion. RESULTS: Pretreatment with either 1 cycle of IPC, LEV (0.1 micromol/kg, i.v.), or IPC+LEV prior to the period of coronary occlusion offers significant infarct size reduction (21.6+/-1.6%, 22.1+/ 2.2%, and 21.4+/-1.4%, respectively vs 38.7+/-3.6% in saline control group; P<0.01) and antiarrhythmic effects. IPC, LEV and IPC+LEV treatment significantly attenuated the incidence of life-threatening arrhythmias like sustained VT (13%, 13% and 13%, respectively vs 100% in saline control group; P<0.005) and other arrhythmias (25%, 25% and 13%, respectively vs 100% in saline control group; P<0.005), and increased the number of surviving animals without arrhythmias. Pretreatment with 5-HD, N(omega)-nitro-L-arginine methyl ester (L-NAME, a nonspecific NOS inhibitor) and the specific iNOS inhibitor 1400 W [N-(-3 (aminomethyl)benzyl) acetamidine] abolished the beneficial effects of IPC, and LEV on reperfusion induced arrhythmias and cardioprotection suggesting that benefits have been achieved via both the selective activation of cardiomyocyte mitochondrial K(ATP) channels and NO. One cycle of IPC and LEV pretreatment significantly preserved the level of ATP in the 30 min ischemic heart and 120 min reperfused heart. CONCLUSIONS: The present study demonstrates similarities between acute LEV treatment and IPC of the rabbit myocardium in terms of survival, cardioprotection, antiarrhythmic activity, and metabolic status. PMID- 17728193 TI - Experience using centralized spirometry in the phase 2 randomized, placebo controlled, double-blind trial of denufosol in patients with mild to moderate cystic fibrosis. AB - BACKGROUND: Centralized spirometry may significantly improve quality of spirometry and reduce variability of this outcome measure in clinical trials in cystic fibrosis (CF). METHODS: Spirometry was performed during the phase 2 randomized, placebo-controlled, double-blind clinical trial of denufosol in patients with mild to moderate CF using American Thoracic Society guidelines. Uniform spirometers were used with electronic data transmission of all the data to a reading center. Spirometry was evaluated for quality by a central reader based on start of test, cough during the test, and evidence of a plateau. RESULTS: A total of 1418 spirometry values were assessed in 89 subjects during the trial. In only 5 instances did the central reading center need to give feedback to sites regarding the quality of spirometry. The study site data matched the central reading center's data for all but 78 (6%) spirometry values in 33 patients. Many of these differences were small with only 35 (3%) values differing by more than 50 mL in 26 patients. CONCLUSION: Spirometry in this clinical trial was of high quality with low rate of significant centralized over read. PMID- 17728192 TI - Electric field-mediated transport of plasmid DNA in tumor interstitium in vivo. AB - Local pulsed electric field application is a method for improving non-viral gene delivery. Mechanisms of the improvement include electroporation and electrophoresis. To understand how electrophoresis affects pDNA delivery in vivo, we quantified the magnitude of electric field-induced interstitial transport of pDNA in 4T1 and B16.F10 tumors implanted in mouse dorsal skin-fold chambers. Four different electric pulse sequences were used in this study, each consisted of 10 identical pulses that were 100 or 400 V/cm in strength and 20 or 50 ms in duration. The interval between consecutive pulses was 1 s. The largest distance of transport was obtained with the 400 V/cm and 50 ms pulse, and was 0.23 and 0.22 microm/pulse in 4T1 and B16.F10 tumors, respectively. There were no significant differences in transport distances between 4T1 and B16.F10 tumors. Results from in vivo mapping and numerical simulations revealed an approximately uniform intratumoral electric field that was predominantly in the direction of the applied field. The data in the study suggested that interstitial transport of pDNA induced by a sequence of ten electric pulses was ineffective for macroscopic delivery of genes in tumors. However, the induced transport was more efficient than passive diffusion. PMID- 17728194 TI - Strategies for improving production and purification of a recombinant protein: rP30 of Toxoplasma gondii expressed in the yeast Schizosaccharomyces pombe. AB - Many problems concerned with the production and the purification of recombinant proteins must be addressed prior to launching an industrial production process. Among these problems, attention is focused on low-level expression that complicates the purification step and can jeopardise the process. The expression of a membrane protein, rP30, of Toxoplasma gondii in the yeast Schizosaccharomyces pombe led to a secretion of only 0.5 microg ml(-1). In order to obtain a sufficient quantity for biochemical characterization and evaluation in vitro diagnostic test development, strategies for both production and purification had to be optimized. First, the influence of four nitrogen sources (three peptones and yeast extract) on the growth rate, but also on the separation between the protein and the components of the fermentation broth was assessed. Second, batch and fed-batch fermentations were compared in terms of final biomass and rP30 concentrations. Third, three different protocols that included fixed and expanded bed ion exchange chromatography were compared for processing a large volume of feedstock. By using the most appropriate strategies, i.e. fed-batch fermentation, capture on EBA cation exchanger and affinity chromatography polishing, a purification factor of 1778 and a yield of 49% were achieved. These performances allowed a 12.5-fold increase for the overall rP30 process productivity. PMID- 17728195 TI - Histidine phosphorylation in biological systems. AB - Histidine phosphorylation is important in prokaryotes and occurs to the extent of 6% of total phosphorylation in eukaryotes. Nevertheless phosphohistidine residues are not normally observed in proteins due to rapid hydrolysis of the phosphoryl group under acidic conditions. Many rapid processes employ phosphohistidines, including the bacterial phosphoenolpyruvate:sugar phosphotransferase system (PTS), the bacterial two-component systems and reactions catalyzed by enzymes such as nucleoside diphosphate kinase and succinyl-CoA synthetase. In the PTS, the NMR structure of the phosphohistidine moiety of the phosphohistidine containing protein was determined but no X-ray structures of phosphohistidine forms of PTS proteins have been elucidated. There have been crystal structures of a few phosphohistidine-containing proteins determined: nucleoside diphosphate kinase, succinyl-CoA synthetase, a cofactor-dependent phosphoglycerate mutase and the protein PAE2307 from the hyperthermophilic archaeon Pyrobaculum aerophilum. A common theme for these stable phosphohistidines is the occurrence of ion-pair hydrogen bonds (salt bridges) involving the non-phosphorylated nitrogen atom of the histidine imidazole ring with an acidic amino acid side chain. PMID- 17728196 TI - Osteoclast-like giant-cell tumour of the pancreas causing painful ampullary obstruction. PMID- 17728197 TI - Distance to public test sites and HIV testing. AB - This article examines how proximity to the nearest publicly funded test site affects HIV testing. Using a sample of 5,361 Los Angeles County adults, multinomial logit models estimated simultaneously the likelihood of (1) obtaining an HIV test in the prior 2 years, and (2) testing in a private physician's office, a publicly funded medical clinic, or in a nonmedical setting, such as a bar or bathhouse. Low-income Los Angeles residents rely on publicly funded sites for HIV testing. When public sites are more distant, poor individuals are less likely to use them and less likely to get tested. Distance from public sites does not affect HIV testing among the nonpoor. To encourage HIV testing among the groups where HIV is growing fastest, public health agencies must keep the time and money costs of HIV testing low. PMID- 17728198 TI - The program success story: a valuable tool for program evaluation. AB - Success stories are evaluation tools that have been used by professionals across disciplines for quite some time. They are also proving to be useful in promoting health programs and their accomplishments. The increasing popularity of success stories is due to the innovative and effective way that they increase a program's visibility, while engaging potential participants, partners, and funders in public health efforts. From the community level to the federal level, program administrators are using success stories as vehicles for celebrating achievements, sharing challenges, and communicating lessons learned. Success stories are an effective means to move beyond the numbers and connect to readers with a cause they can relate to and want to join. This article defines success stories and provides an overview of several types of story formats, how success stories can be systematically collected, and how they are used to communicate program success. PMID- 17728199 TI - Addressing food security through public policy action in a community-based participatory research partnership. AB - Community-based participatory research (CBPR) is an increasingly utilized research approach that involves the affected community identifying a health related problem, developing a research agenda, and planning an appropriate intervention to address the problem. This report on a CBPR partnership in San Francisco's Bayview Hunters Point neighborhood documents the rise of a community food security policy in response to youth-involved research that found poor access to quality food in an economically disadvantaged area of the city. To analyze the impact of the research on public policy, a framework of specific steps in the policy-making process is used to organize and better understand the partnership's objectives, activities, strategies, and successes. This community health department partnership has been able to achieve an innovative and sustainable public policy solution, the Good Neighbor Program, by working closely with policy makers and local businesses to expand community accessibility to healthy food. PMID- 17728200 TI - Improving nutrition education newsletters for the food stamp eligible audience. AB - The purpose of this study was to identify the types of nutrition newsletter content that reading clientele perceive as relevant to them in making healthy food choices consistent with sound dietary advice, and to identify ways newsletter design and wording affect the usefulness of the content. The authors conducted five focus groups with readers of nutrition education newsletters in three different regions of Pennsylvania between January and April 2003. All participants were obtaining food from their community food pantry, where newsletters are distributed by the Pennsylvania Nutrition Education Program. Major nutrition and health concerns of participants included heart disease, diabetes, dietary fat, and sodium intake. Recipes are the most highly valued portion of the newsletters. To summarize, newsletter readers indicate that effectiveness in facilitating food and nutrition behavior change is a function of the relevance, design, and practicality of the content. PMID- 17728201 TI - How using a logic model refined our program to ensure success. AB - When a program does not produce expected changes in the outcomes of interest, program staff must understand why before making programmatic decisions. One mechanism for doing so is the logic model. This article describes how using one such logic model (the ATM approach) was used to improve areas of program planning and implementation. The key components include interviewing stakeholders to identify antecedent conditions to the problem of interest that are placed in a summary map and then prioritizing those conditions to address with program activities. Although the logic modeling process was helpful in making programmatic improvements, there were also several unintended benefits of engaging in the process including: providing a framework for planning and evaluation, helping the program operate more effectively and efficiently, and providing a common language among program staff and the evaluators. PMID- 17728202 TI - A state-based model of prevention: Indiana's example. AB - Public health officials in the United States have battled alcohol, tobacco, and other drug (ATOD) use among adolescents for the past few decades, but only in 2002 did they begin to see a decline in rates of use. ATOD use and abuse are associated with numerous problems, including criminal behavior and increased adolescent morbidity and mortality rates. Researchers have sought to identify best-practice procedures for ATOD prevention; the state of Indiana has a strong ATOD prevention system in place that has the potential to serve as a model for other U.S. localities because of its best-practice approach to public health services. This article outlines the activities of the Indiana Prevention Resource Center to provide an example to strengthen public health professionals' ability to prevent ATOD use and abuse and to provide for a healthy adolescent population. PMID- 17728203 TI - An evaluation of community health center adoption of online health information. AB - Health care providers and patients in community health centers often lack access to online scientific and patient education resources. These resources can improve medical decision making and promote communication between provider and patient. In 2000, a community health information program, Partners for Health Information, provided 10 community health centers in Washington, D.C. with computers, training, and consumer health resources, supplemented with visits to coach patients and staff in their use. The purpose of this study is to assess the adoption of the use of online health information among staff in seven of these health centers. The methods of this evaluation were designed to measure frequency of patient referral by health center staff to online health information and to describe providers' perceptions of the barriers and enablers to using online resources. Recommendations made by respondents can be used to modify the Partners program and guide the development of other similar programs. PMID- 17728204 TI - Physical activity influences in a disadvantaged African American community and the communities' proposed solutions. AB - The purpose of this assessment is to increase our understanding of how safety and environmental factors influence physical activity among African American residents living in a low-income, high-crime neighborhood and to get input from these residents about how to best design physical activity interventions for their neighborhood. Twenty-seven African American adult residents of a low income, high-crime neighborhood in a suburban southeastern community participated in three focus groups. Participants were asked questions about perceptions of what would help them, their families, and their neighbors be more physically active. Two independent raters coded the responses into themes. Participants suggested three environmental approaches in an effort to increase physical activity: increasing law enforcement, community connectedness and social support, and structured programs. Findings suggest that safety issues are an important factor for residents living in disadvantaged conditions and that the residents know how they want to make their neighborhoods healthier. PMID- 17728205 TI - Sixth biannual report of the Cochrane Haematological Malignancies Group--focus on non-Hodgkin lymphoma. PMID- 17728206 TI - NCI director opts against breast cancer prevention trial in favor of biomarkers. PMID- 17728207 TI - Notch emerges as new cancer drug target. PMID- 17728208 TI - Generic biologics may be coming to the marketplace if legislation passes in Congress. PMID- 17728209 TI - Pregnancy problem yields insight into cancer drug induced high blood pressure. PMID- 17728210 TI - Stat bite: Patients' plans for frozen embryos. PMID- 17728211 TI - The mind prepared: hypnosis in surgery. PMID- 17728212 TI - Is a screening interval of every 4 years for prostate cancer acceptable? PMID- 17728213 TI - Helicobacter pylori cytotoxin-associated genotype and gastric precancerous lesions. AB - BACKGROUND: Helicobacter pylori infection is associated with the development of gastric cancer. Although infection with an H. pylori strain containing the cytotoxin-associated (cag A) gene (a marker for a pathogenicity island) may increase the risk of atrophic gastritis and gastric cancer, the relationship of variants in pathogenic H. pylori genes to the severity and progression of precancerous lesions is not well defined. METHODS: Gastric biopsy specimens were obtained at enrollment from 2145 participants in a chemoprevention trial in Tachira State, Venezuela, and examined histologically to determine the severity of precancerous lesions. The presence of H. pylori DNA in gastric biopsies and the strain type according to presence or absence of the cagA gene were detected by polymerase chain reaction and specific probes. The relationship between H. pylori DNA and histologic diagnosis was analyzed by polytomous logistic regression. Rates of progression and regression of precancerous lesions were determined from biopsies from additional annual gastroscopies (mean follow-up = 3.5 years). All statistical tests were two-sided. RESULTS: At enrollment, there was a strong association between cagA-positive H. pylori infection and the severity of gastric precancerous lesions, but cagA-negative H. pylori was associated only with chronic gastritis. Using individuals with normal mucosa or superficial gastritis as control subjects, the odds ratio for dysplasia was 15.5 (95% confidence interval [CI] = 6.42 to 37.2) in cagA-positive individuals compared with uninfected individuals and 0.90 (95% CI = 0.37 to 2.17) for individuals infected with cagA-negative H. pylori compared with uninfected individuals. Individuals infected with cagA-positive H. pylori appeared more likely to experience progression (and less likely to experience regression) of precancerous lesions than those infected with cagA-negative H. pylori, but the differences did not attain statistical significance. CONCLUSIONS: This large epidemiologic study shows a strong relationship between the presence of H. pylori DNA in gastric biopsies and the severity of precancerous lesions that is specific to cagA-positive strains. The association between H. pylori and gastric carcinoma may have been previously underestimated due to the poor accuracy of serologic H. pylori markers and lack of discrimination by cagA genotype. PMID- 17728214 TI - UGT1A1*28 genotype and irinotecan-induced neutropenia: dose matters. AB - The Food and Drug Administration and Pfizer changed the package insert for irinotecan to include a patient's UGT1A1*28 genotype as a risk factor for severe neutropenia on the basis of the findings of four pharmacogenetic studies, which found that irinotecan-treated patients who were homozygous for the UGT1A1*28 allele had a greater risk of hematologic toxic effects than patients who had one or two copies of the wild-type allele (UGT1A1*1). Findings of subsequent irinotecan pharmacogenetic studies have been inconsistent. In a meta-analysis, we reviewed data presented in nine studies that included a total of 10 sets of patients (for a total of 821 patients) and assessed the association of irinotecan dose with the risk of irinotecan-related hematologic toxicities (grade III-IV) for patients with a UGT1A1*28/*28 genotype. The risk of toxicity was higher among patients with a UGT1A1*28/*28 genotype than among those with a UGT1A1*1/*1 or UGT1A1*1/*28 genotype at both medium (odds ratio [OR] = 3.22, 95% confidence interval [CI] = 1.52 to 6.81; P = .008) and high (OR = 27.8, 95% CI = 4.0 to 195; P = .005) doses of irinotecan. However, risk was similar at lower doses (OR = 1.80, 95% CI = 0.37 to 8.84; P = .41). Low doses of irinotecan (100-125 mg/m2) are in the commonly used therapeutic range. The risk of experiencing irinotecan induced hematologic toxicity for patients with a UGT1A1*28/*28 genotype thus appears to be a function of the dose of irinotecan administered. PMID- 17728215 TI - Ovarian cancer G protein-coupled receptor 1, a new metastasis suppressor gene in prostate cancer. AB - BACKGROUND: Metastasis is a process by which tumors spread from primary organs to other sites in the body and is the major cause of death for cancer patients. The ovarian cancer G protein-coupled receptor 1 (OGR1) gene has been shown to be expressed at lower levels in metastatic compared with primary prostate cancer tissues. METHODS: We used an orthotopic mouse metastasis model, in which we injected PC3 metastatic human prostate cancer cells stably transfected with empty vector (vector-PC3) or OGR1-expressing vector (OGR1-PC3) into the prostate lobes of athymic or NOD/SCID mice (n = 3-8 mice per group). Migration of PC3 cells transiently transfected with vector control or with OGR1- or GPR4 (a G protein coupled receptor with the highest homology to OGR1)-expressing vectors was measured in vitro by Boyden chamber assays. G protein alpha-inhibitory subunit 1 (G alpha(i1)) expression after treatment with pertussis toxin (PTX) was measured using immunoblotting analysis. The inhibitory factor present in the conditioned medium was extracted using organic solvents and analyzed by mass spectrometry. RESULTS: In vivo, all 26 mice carrying tumors that were derived from vector-PC3 cells developed prostate cancer metastases (mean = 100%, 95% confidence interval [CI] = 83.97% to 100%) but few (4 of 32) mice carrying tumors derived from OGR1 expressing PC3 cells (mean = 12.50%, 95% CI = 4.08% to 29.93%) developed metastases. However, exogenous OGR1 overexpression had no effect on primary prostate tumor growth in vivo. In vitro, expression of OGR1, but not GPR4, inhibited cell migration (mean percentage of cells migrated, 30.2% versus 100%, difference = 69.8%, 95% CI = 63.0% to 75.9%; P<.001) via increased expression of G alpha(i1) and the secretion of a chloroform/methanol-extractable heat insensitive factor into the conditioned medium through a PTX-sensitive pathway. CONCLUSION: OGR1 is a novel metastasis suppressor gene for prostate cancer. OGR1's constitutive activity via G alpha(i) contributes to its inhibitory effect on cell migration in vitro. PMID- 17728217 TI - Re: Ovarian ablation or suppression in premenopausal early breast cancer: results from the International Adjuvant Breast Cancer Ovarian Ablation or Suppression randomized trial. PMID- 17728216 TI - A randomized clinical trial of a brief hypnosis intervention to control side effects in breast surgery patients. AB - BACKGROUND: Breast cancer surgery is associated with side effects, including postsurgical pain, nausea, and fatigue. We carried out a randomized clinical trial to test the hypotheses that a brief presurgery hypnosis intervention would decrease intraoperative anesthesia and analgesic use and side effects associated with breast cancer surgery and that it would be cost effective. METHODS: We randomly assigned 200 patients who were scheduled to undergo excisional breast biopsy or lumpectomy (mean age 48.5 years) to a 15-minute presurgery hypnosis session conducted by a psychologist or nondirective empathic listening (attention control). Patients were not blinded to group assignment. Intraoperative anesthesia use (i.e., of the analgesics lidocaine and fentanyl and the sedatives propofol and midazolam) was assessed. Patient-reported pain and other side effects as measured on a visual analog scale (0-100) were assessed at discharge, as was use of analgesics in the recovery room. Institutional costs and time in the operating room were assessed via chart review. RESULTS: Patients in the hypnosis group required less propofol (means = 64.01 versus 96.64 microg; difference = 32.63; 95% confidence interval [CI] = 3.95 to 61.30) and lidocaine (means = 24.23 versus 31.09 mL; difference = 6.86; 95% CI = 3.05 to 10.68) than patients in the control group. Patients in the hypnosis group also reported less pain intensity (means = 22.43 versus 47.83; difference = 25.40; 95% CI = 17.56 to 33.25), pain unpleasantness (means = 21.19 versus 39.05; difference = 17.86; 95% CI = 9.92 to 25.80), nausea (means = 6.57 versus 25.49; difference = 18.92; 95% CI = 12.98 to 24.87), fatigue (means = 29.47 versus 54.20; difference = 24.73; 95% CI = 16.64 to 32.83), discomfort (means = 23.01 versus 43.20; difference = 20.19; 95% CI = 12.36 to 28.02), and emotional upset (means = 8.67 versus 33.46; difference = 24.79; 95% CI = 18.56 to 31.03). No statistically significant differences were seen in the use of fentanyl, midazolam, or recovery room analgesics. Institutional costs for surgical breast cancer procedures were $8561 per patient at Mount Sinai School of Medicine. Patients in the hypnosis group cost the institution $772.71 less per patient than those in the control group (95% CI = 75.10 to 1469.89), mainly due to reduced surgical time. CONCLUSIONS: Hypnosis was superior to attention control regarding propofol and lidocaine use; pain, nausea, fatigue, discomfort, and emotional upset at discharge; and institutional cost. Overall, the present data support the use of hypnosis with breast cancer surgery patients. PMID- 17728218 TI - Interval cancers in prostate cancer screening: comparing 2- and 4-year screening intervals in the European Randomized Study of Screening for Prostate Cancer, Gothenburg and Rotterdam. AB - BACKGROUND: The incidence of prostate cancer has increased substantially since it became common practice to screen asymptomatic men for the disease. The European Randomized Study of Screening for Prostate Cancer (ERSPC) was initiated in 1993 to determine how prostate-specific antigen (PSA) screening affects prostate cancer mortality. Variations in the screening algorithm, such as the interval between screening rounds, likely influence the morbidity, mortality, and quality of life of the screened population. METHODS: We compared the number and characteristics of interval cancers, defined as those diagnosed during the screening interval but not detected by screening, in men in the screening arm of the ERSPC who were aged 55-65 years at the time of the first screening and were participating through two centers of the ERSPC: Gothenburg (2-year screening interval, n = 4202) and Rotterdam (4-year screening interval, n = 13301). All participants who were diagnosed with prostate cancer through December 31, 2005, but at most 10 years after the initial screening were ascertained by linkage with the national cancer registries. A potentially life-threatening (aggressive) interval cancer was defined as one with at least one of the following characteristics at diagnosis: stage M1 or N1, plasma PSA concentration greater than 20.0 ng/mL, or Gleason score greater than 7. We used Mantel Cox regression to assess differences between rates of interval cancers and aggressive interval cancers at the two centers. All statistical tests were two-sided. RESULTS: The 10 year cumulative incidence of all prostate cancers in Rotterdam versus Gothenburg was 1118 (8.41%) versus 552 (13.14%) (P<.001), the cumulative incidence of interval cancer was 57 (0.43%) versus 31 (0.74%) (P = .51), and the cumulative incidence of aggressive interval cancer was 15 (0.11%) versus 5 (0.12%) (P = .72). CONCLUSION: The rate of interval cancer, especially aggressive interval cancer, was low in this study. The 2-year screening interval had higher detection rates than the 4-year interval but did not lead to lower rates of interval and aggressive interval prostate cancers. PMID- 17728219 TI - Re: Adjuvant treatment of high-risk, radically resected gastric cancer patients with 5-fluorouracil, leucovorin, cisplatin, and epidoxorubicin in a randomized controlled trial. PMID- 17728220 TI - Re: Decreased STAT1 expression by promoter methylation in squamous cell carcinogenesis. PMID- 17728221 TI - Human immunodeficiency virus type 1 controllers but not noncontrollers maintain CD4 T cells coexpressing three cytokines. AB - Here, we evaluate the cytokine coexpression profiles of human immunodeficiency virus (HIV)-specific CD4 T cells for the expression of the cytokines gamma interferon (IFN-gamma), interleukin-2, and tumor necrosis factor alpha. In controllers, CD4 T cells producing three or two cytokines (triple producers and double producers, respectively) represented >50% of the total response. In contrast, in noncontrollers approximately 75% of responding cells produced only one cytokine (single producers), mostly IFN-gamma. Cells producing three cytokines were functionally superior to those producing single cytokines and showed an inverse correlation (P < 0.001) with viral load. These results demonstrate a strong association between the maintenance of highly functional CD4 T cells producing three cytokines and control of HIV-1. PMID- 17728222 TI - Evolution of human immunodeficiency virus type 1 cytotoxic T-lymphocyte epitopes: fitness-balanced escape. AB - CD8(+) cytotoxic T lymphocytes (CTL) are strong mediators of human immunodeficiency virus type 1 (HIV-1) control, yet HIV-1 frequently mutates to escape CTL recognition. In an analysis of sequences in the Los Alamos HIV-1 database, we show that emerging CTL escape mutations were more often present at lower frequencies than the amino acid(s) that they replaced. Furthermore, epitopes that underwent escape contained amino acid sites of high variability, whereas epitopes persisting at high frequencies lacked highly variable sites. We therefore infer that escape mutations are likely to be associated with weak functional constraints on the viral protein. This was supported by an extensive analysis of one subject for whom all escape mutations within defined CTL epitopes were studied and by an analysis of all reported escape mutations of defined CTL epitopes in the HIV Immunology Database. In one of these defined epitopes, escape mutations involving the substitution of amino acids with lower database frequencies occurred, and the epitope soon reverted back to the sensitive form. We further show that this escape mutation substantially diminished viral fitness in in vitro competition assays. Coincident with the reversion in vivo, we observed the fixation of a mutation 3 amino acids C terminal to the epitope, coincident with the ablation of the corresponding CTL response. The C-terminal mutation did not restore replication fitness reduced by the escape mutation in the epitope and by itself had little effect on replication fitness. Therefore, this C-terminal mutation presumably impaired the processing and presentation of the epitope. Finally, for one persistent epitope, CTL cross-reactivity to a mutant form may have suppressed the mutant to undetected levels, whereas for two other persistent epitopes, each of two mutants showed poor cross-reactivity and appeared in the subject at later time points. Thus, a viral dynamic exists between the advantage of immune escape, peptide cross-reactivity, and the disadvantage of lost replication fitness, with the balance playing an important role in determining whether a CTL epitope will persist or decline during infection. PMID- 17728223 TI - Inhibition of foot-and-mouth disease virus infections in cell cultures with antisense morpholino oligomers. AB - Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven hoofed ungulates that can lead to severe losses in the livestock production and export industries. Although vaccines have been extensively used to control FMD, there is no antiviral therapy available to treat ongoing infections with FMD virus (FMDV). Six peptide-conjugated morpholino oligomers (PPMOs) with sequences complementary to various 21-nucleotide segments of the 5' and 3' untranslated regions (UTRs) of the FMDV genome (strain A(24) Cruzeiro/Brazil/1955 [A(24)Cru]) were evaluated in cell cultures. Three of the PPMOs, targeting domain 5 of the internal ribosome entry site (5D PPMO), and the two translation start codon regions (AUG1 and AUG2 PPMOs), showed high levels of anti-FMDV activity. A dose dependent and sequence-specific reduction in viral titers of greater than 5 log(10), with a concomitant reduction of viral protein and RNA expression, was achieved at low micromolar concentrations. Under identical conditions, three other PPMOs targeting the 5'-terminal region of the genome, the cis-acting replication element in the 5' UTR, and the 3' "ab" stem-loop showed less dramatic titer reductions of 1.5 log(10) to 2 log(10). Treatment with 5D PPMO reduced the titers of FMDV strains representing five different serotypes by 2 log(10) to 4 log(10) compared to those of the controls. A(24)Cru-infected BHK-21 cells treated repeatedly with 5D or AUG2 PPMO generated resistant viruses for which phenotypic and genotypic properties were defined. Notably, three passages with low concentrations of the AUG1 PPMO extinguished all traces of detectable virus. The results indicate that PPMOs have potential for treating FMDV infections and that they also represent useful tools for studying picornaviral translation and evolution. PMID- 17728224 TI - An active TRIM5 protein in rabbits indicates a common antiviral ancestor for mammalian TRIM5 proteins. AB - The recent identification of antiretroviral tripartite motif-bearing restriction factors that protect against retroviral infection has revealed a novel branch of innate immunity. The factors target the retroviral capsid and inhibit infectivity soon after the capsid has entered the cytoplasm by an incompletely characterized mechanism. Restriction is species specific. For example, TRIM5alpha from Old World monkeys, but not humans, restricts human immunodeficiency virus type 1 infection. Here, we identify an antiviral TRIM5 molecule in rabbits that is closely related to antiviral TRIM5 of both primates and cattle. We demonstrate that the rabbit TRIM5 protein is active against divergent retroviruses and leads to a strong block to viral DNA synthesis and infectivity. Furthermore, we show that antiviral activity is directed against the viral capsid and that human TRIM5 proteins are dominant negative to restriction in rabbit cells. We propose that the sequence and restriction characteristics conserved between restriction factors from primates, cattle, and rabbits indicate that these factors have evolved from a common ancestor with antiretroviral properties. PMID- 17728225 TI - Induction of CD8+ cells able to suppress CCR5-tropic simian immunodeficiency virus SIVmac239 replication by controlled infection of CXCR4-tropic simian-human immunodeficiency virus in vaccinated rhesus macaques. AB - Recent recombinant viral vector-based AIDS vaccine trials inducing cellular immune responses have shown control of CXCR4-tropic simian-human immunodeficiency virus (SHIV) replication but difficulty in containment of pathogenic CCR5-tropic simian immunodeficiency virus (SIV) in rhesus macaques. In contrast, controlled infection of live attenuated SIV/SHIV can confer the ability to contain SIV superchallenge in macaques. The specific immune responses responsible for this control may be induced by live virus infection but not consistently by viral vector vaccination, although those responses have not been determined. Here, we have examined in vitro anti-SIV efficacy of CD8+ cells in rhesus macaques that showed prophylactic viral vector vaccine-based control of CXCR4-tropic SHIV89.6PD replication. Analysis of the effect of CD8+ cells obtained at several time points from these macaques on CCR5-tropic SIVmac239 replication in vitro revealed that CD8+ cells in the chronic phase after SHIV challenge suppressed SIV replication more efficiently than those before challenge. SIVmac239 superchallenge of two of these macaques at 3 or 4 years post-SHIV challenge was contained, and the following anti-CD8 antibody administration resulted in transient CD8+ T-cell depletion and appearance of plasma SIVmac239 viremia in both of them. Our results indicate that CD8+ cells acquired the ability to efficiently suppress SIV replication by controlled SHIV infection, suggesting the contribution of CD8+ cell responses induced by controlled live virus infection to containment of HIV/SIV superinfection. PMID- 17728226 TI - Mouse-adapted ovine scrapie prion strains are characterized by different conformers of PrPSc. AB - The agent responsible for prion disease may exist in different forms, commonly referred to as strains, with each carrying the specific information that determines its own distinct biological properties, such as incubation period and lesion profile. Biological strain typing of ovine scrapie isolates by serial passage in conventional mice has shown some diversity in ovine prion strains. However, this biological diversity remains poorly supported by biochemical prion strain typing. The protein-only hypothesis predicts that variation between different prion strains in the same host is manifest in different conformations adopted by PrPSc. Here we have investigated the molecular properties of PrPSc associated with two principal Prnp(a) mouse-adapted ovine scrapie strains, namely, RML and ME7, in order to establish biochemical prion strain typing strategies that may subsequently be used to discriminate field cases of mouse passaged ovine scrapie isolates. We used a conformation-dependent immunoassay and a conformational stability assay, together with Western blot analysis, to demonstrate that RML and ME7 PrPSc proteins show distinct biochemical and physicochemical properties. Although RML and ME7 PrPSc proteins showed similar resistance to proteolytic digestion, they differed in their glycoform profiles and levels of proteinase K (PK)-sensitive and PK-resistant isoforms. In addition, the PK-resistant core (PrP27-30) of ME7 was conformationally more stable following exposure to guanidine hydrochloride or Sarkosyl than was RML PrP27-30. Our data show that mouse-adapted ovine scrapie strains can be discriminated by their distinct conformers of PrPSc, which provides a basis to investigate their diversity at the molecular level. PMID- 17728227 TI - Recovery of Nicotiana benthamiana plants from a necrotic response induced by a nepovirus is associated with RNA silencing but not with reduced virus titer. AB - Recovery of plants from virus-induced symptoms is often described as a consequence of RNA silencing, an antiviral defense mechanism. For example, recovery of Nicotiana clevelandii from a nepovirus (tomato black ring virus) is associated with a decreased viral RNA concentration and sequence-specific resistance to further virus infection. In this study, we have characterized the interaction of another nepovirus, tomato ringspot virus (ToRSV), with host defense responses during symptom induction and subsequent recovery. Early in infection, ToRSV induced a necrotic phenotype in Nicotiana benthamiana that showed characteristics typical of a hypersensitive response. RNA silencing was also activated during ToRSV infection, as evidenced by the presence of ToRSV derived small interfering RNAs (siRNAs) that could direct degradation of ToRSV sequences introduced into sensor constructs. Surprisingly, disappearance of symptoms was not accompanied by a commensurate reduction in viral RNA levels. The stability of ToRSV RNA after recovery was also observed in N. clevelandii and Cucumis sativus and in N. benthamiana plants carrying a functional RNA-dependent RNA polymerase 1 ortholog from Medicago truncatula. In experiments with a reporter transgene (green fluorescent protein), ToRSV did not suppress the initiation or maintenance of transgene silencing, although the movement of the silencing signal was partially hindered. Our results demonstrate that although RNA silencing is active during recovery, reduction of virus titer is not required for the initiation of this phenotype. This scenario adds an unforeseen layer of complexity to the interaction of nepoviruses with the host RNA silencing machinery. The possibility that viral proteins, viral RNAs, and/or virus-derived siRNAs inactivate host defense responses is discussed. PMID- 17728228 TI - Identification of acetylated, tetrahalogenated benzimidazole D-ribonucleosides with enhanced activity against human cytomegalovirus. AB - DNA packaging is the key step in viral maturation and involves binding and cleavage of viral DNA containing specific DNA-packaging motifs. This process is mediated by a group of specific enzymes called terminases. We previously demonstrated that the human cytomegalovirus (HCMV) terminase is composed of the large subunit pUL56 and the small subunit pUL89. While the large subunit mediates sequence-specific DNA binding and ATP hydrolysis, pUL89 is required only for duplex nicking. An excellent inhibitor targeting HCMV terminase is 2-bromo-5,6 dichloro-1-(beta-d-ribofuranosyl)benzimidazole (BDCRB), but it was not developed as an antiviral drug due to its metabolic cleavage in experimental animals. We now have tested several new benzimidazole d-ribonucleosides in order to determine whether these compounds represent new, potent inhibitors. Analysis by bioluminometric ATPase activity assays identified two of the new compounds with a high inhibitory effect, 2-bromo-4,5,6-trichloro-1-(2,3,5-tri-O-acetyl-beta-D ribofuranosyl) benzimidazole (BTCRB) and 2,4,5,6-tetrachloro-1-(2,3,5-tri-O acetyl-beta-D-ribofuranosyl benzimidazole (Cl(4)RB). By using viral plaque formation, viral yield, and viral growth kinetics, we demonstrated that the two compounds BTCRB and Cl(4)RB had antiviral activities similar to that of BDCRB. Interestingly, BTCRB retained its inhibitory activity after preincubation with HFF cells. By use of electron microscopy, we observed an increase of B capsids and a lack of cytoplasmic capsids in the presence of the compounds that correlated with the virus yield. Furthermore, cleavage of concatenated DNA was inhibited by both compounds, and inhibition by BTCRB was shown to be dose dependent. These results demonstrate that the new compounds are highly active against HCMV and act by mechanisms similar but not identical to those of BDCRB. PMID- 17728229 TI - Myxoma virus expressing human interleukin-12 does not induce myxomatosis in European rabbits. AB - Myxoma virus (MV) is a candidate for oncolytic virotherapy due to its ability to selectively infect and kill tumor cells, yet MV is a species-specific pathogen that causes disease only in European rabbits. To assess the ability of MV to deliver cytokines to tumors, we created an MV (vMyxIL-12) that expresses human interleukin-12 (IL-12). vMyxIL-12 replicates similarly to wild-type MV, and virus infected cells secrete bioactive IL-12. Yet, vMyxIL-12 does not cause myxomatosis, despite expressing the complete repertoire of MV proteins. Thus, vMyxIL-12 exhibits promise as an oncolytic candidate and is safe in all known vertebrate hosts, including lagomorphs. PMID- 17728230 TI - Identification of an arsenic-sensitive block to primate lentiviral infection of human dendritic cells. AB - Dendritic cells are central to the early events of human immunodeficiency virus type 1 (HIV-1) transmission, but HIV-1 infects dendritic cells inefficiently in vitro compared to activated CD4(+) T cells. There is a strong postentry restriction of HIV-1 infection in dendritic cells, partly mediated by the cellular restriction factor APOBEC3G. Here, we reveal that arsenic trioxide markedly increases HIV infection of immature and mature dendritic cells as well as blood-derived myeloid dendritic cells in an APOBEC3G- and TRIM5alpha independent way. Our data suggest the presence of powerful, arsenic-sensitive antiviral activities in primary human immune cells of the dendritic cell lineage. PMID- 17728231 TI - Characterization of low-pathogenicity H5N1 avian influenza viruses from North America. AB - Wild-bird surveillance in North America for avian influenza (AI) viruses with a goal of early identification of the Asian H5N1 highly pathogenic AI virus has identified at least six low-pathogenicity H5N1 AI viruses between 2004 and 2006. The hemagglutinin (HA) and neuraminidase (NA) genes from all 6 H5N1 viruses and an additional 38 North American wild-bird-origin H5 subtype and 28 N1 subtype viruses were sequenced and compared with sequences available in GenBank by phylogenetic analysis. Both HA and NA were phylogenetically distinct from those for viruses from outside of North America and from those for viruses recovered from mammals. Four of the H5N1 AI viruses were characterized as low pathogenicity by standard in vivo pathotyping tests. One of the H5N1 viruses, A/MuteSwan/MI/451072-2/06, was shown to replicate to low titers in chickens, turkeys, and ducks. However, transmission of A/MuteSwan/MI/451072-2/06 was more efficient among ducks than among chickens or turkeys based on virus shed. The 50% chicken infectious dose for A/MuteSwan/MI/451072-2/06 and three other wild waterfowl-origin H5 viruses were also determined and were between 10(5.3) and 10(7.5) 50% egg infective doses. Finally, seven H5 viruses representing different phylogenetic clades were evaluated for their antigenic relatedness by hemagglutination inhibition assay, showing that the antigenic relatedness was largely associated with geographic origin. Overall, the data support the conclusion that North American H5 wild-bird-origin AI viruses are low pathogenicity wild-bird-adapted viruses and are antigenically and genetically distinct from the highly pathogenic Asian H5N1 virus lineage. PMID- 17728232 TI - Escape and compensation from early HLA-B57-mediated cytotoxic T-lymphocyte pressure on human immunodeficiency virus type 1 Gag alter capsid interactions with cyclophilin A. AB - Certain histocompatibility leukocyte antigen (HLA) alleles are associated with improved clinical outcomes for individuals infected with human immunodeficiency virus type 1 (HIV-1), but the mechanisms for their effects remain undefined. An early CD8(+) T-cell escape mutation in the dominant HLA-B57-restricted Gag epitope TW10 (TSTLQEQIGW) has been shown to impair HIV-1 replication capacity in vitro. We demonstrate here that this T(242)N substitution in the capsid protein is associated with upstream mutations at residues H(219), I(223), and M(228) in the cyclophilin A (CypA)-binding loop in B57(+) individuals with progressive disease. In an independent cohort of epidemiologically linked transmission pairs, the presence of these substitutions in viruses encoding T(242)N was associated with significantly higher plasma viremia in donors, further suggesting that these secondary mutations compensated for the replication defect of T(242)N. Using NL4 3 constructs, we illustrate the ability of these CypA loop changes to partially restore replication of the T(242)N variant in vitro. Notably, these mutations also enhanced viral resistance to the drug cyclosporine A, indicating a reduced dependence of the compensated virus on CypA that is normally essential for optimal infectivity. Therefore, mutations in TW10 allow HIV-1 to evade a dominant early CD8(+) T-cell response, but the benefits of escape are offset by a defect in capsid function. These data suggest that TW10 escape variants undergo a postentry block that is partially overcome by changes in the CypA-binding loop and identify a mechanism for an HIV-1 fitness defect that may contribute to the slower disease progression associated with HLA-B57. PMID- 17728233 TI - Sequence of human immunodeficiency virus type 1 (HIV-1) Gag localization and oligomerization monitored with live confocal imaging of a replication-competent, fluorescently tagged HIV-1. AB - The assembly of infectious human immunodeficiency virus (HIV) requires that Gag transport and oligomerization be coordinated with its association with other viral proteins, viral RNAs, and cellular membranes. We have developed a replication-competent HIV type 1 molecular clone that carries a Gag-internal or interdomain green fluorescent protein (iGFP) fusion to reveal a physiologically accurate temporal sequence of Gag localization and oligomerization during the formation of infectious HIV. This recombinant HIV is as infectious as native HIV in single-round infectivity assays, validating its use for trafficking studies. It replicates robustly in permissive MT4 cells and is infectious, yet it spreads poorly in other T-cell lines. Immunofluorescence of Gag-iGFP showed a pattern very similar to that of native Gag. However, the intense plasma membrane Gag-iGFP fluorescence contrasts markedly with its immunofluorescence at this site, indicating that many Gag epitopes can be masked by oligomerization. Consistent with this, fluorescence resonance energy transfer studies visualized intense Gag oligomerization at the plasma membrane and weaker oligomerization at cytoplasmic sites. Four-dimensional, time-lapse confocal imaging reveals a temporal progression of Gag distribution over hours in which Gag is initially diffusely localized within the cytoplasm. Plasma membrane signals then accumulate as Gag levels increase and vesicular association appears late, only after plasma membrane site signals have reached high intensity. Lastly, the cell rounds up and HIV protease activation induces diffuse fluorescence throughout the cell. These distinct phases reveal a natural progression of Gag trafficking during the viral gene expression program. HIV Gag-iGFP is a useful tool for dissecting mechanisms of viral assembly and transmission. PMID- 17728234 TI - Nuclear magnetic resonance structure of the N-terminal domain of nonstructural protein 3 from the severe acute respiratory syndrome coronavirus. AB - This paper describes the structure determination of nsp3a, the N-terminal domain of the severe acute respiratory syndrome coronavirus (SARS-CoV) nonstructural protein 3. nsp3a exhibits a ubiquitin-like globular fold of residues 1 to 112 and a flexibly extended glutamic acid-rich domain of residues 113 to 183. In addition to the four beta-strands and two alpha-helices that are common to ubiquitin-like folds, the globular domain of nsp3a contains two short helices representing a feature that has not previously been observed in these proteins. Nuclear magnetic resonance chemical shift perturbations showed that these unique structural elements are involved in interactions with single-stranded RNA. Structural similarities with proteins involved in various cell-signaling pathways indicate possible roles of nsp3a in viral infection and persistence. PMID- 17728235 TI - Cardiovirus 2A protein associates with 40S but not 80S ribosome subunits during infection. AB - Host translation shutoff induced in picornavirus-infected cells is a well-known phenomenon. The mechanisms by which separate genera of the picornavirus family achieve this shutoff differ. This study examined alterations in the cellular translational components in HeLa cells infected with encephalomyocarditis virus (EMCV), a cardiovirus. In agreement with previous reports, EMCV induced a marked decrease in host mRNA translation. The inhibition correlated with the appearance of a significantly enhanced 80S peak in cells and a concomitant decrease in polysome abundance. Characterization of the 80S material revealed that these ribosomes were virtually devoid of mRNA. Viral protein 2A was tightly associated with some of the free 40S ribosome subunits, but it was not present in the 80S pool which accumulated after infection. Expression of 2A protein in cells in the absence infection was able to modulate the cellular translational environment to increase the ratio of internal ribosome entry site-dependent translation to cap dependent translation of a reporter construct. The results provide further evidence for a role of 2A protein in the mechanism of cardiovirus-induced host translational shutoff. PMID- 17728237 TI - Characterization of hepatitis C virus deletion mutants circulating in chronically infected patients. AB - Hepatitis C virus (HCV) has a linear positive-stranded RNA genome of approximately 9,600 nucleotides in length and displays a high level of sequence diversity caused by high mutation rates and recombination. However, when we performed long distance reverse transcription-PCRs on HCV RNA isolated from serum of chronic HCV patients, not only full-length HCV genomes but also HCV RNAs which varied in size from 7,600 to 8,346 nucleotides and contained large in-frame deletions between E1 and NS2 were amplified. Carefully designed control experiments indicated that these deletion mutants are a bona fide natural RNA species, most likely packaged in virions. Moreover, deletion mutants were detected in sera of patients infected with different HCV genotypes. We observed that 7/37 (18.9%) of genotype 1, 5/43 (11.6%) of genotype 3, and 4/13 (30.7%) of genotype 6 samples contained HCV deletion mutant genomes. These observations further exemplify HCV's huge genetic diversity and warrant studies to explore their biological relevance. PMID- 17728236 TI - The level of friend retrovirus replication determines the cytolytic pathway of CD8+ T-cell-mediated pathogen control. AB - Cytotoxic T cells (CTL) play a central role in the control of viral infections. Their antiviral activity can be mediated by at least two cytotoxic pathways, namely, the granule exocytosis pathway, involving perforin and granzymes, and the Fas-FasL pathway. However, the viral factor(s) that influences the selection of one or the other pathway for pathogen control is elusive. Here we investigate the role of viral replication levels in the induction and activation of CTL, including their effector potential, during acute Friend murine leukemia virus (F MuLV) infection. F-MuLV inoculation results in a low-level infection of adult C57BL/6 mice that is enhanced about 500-fold upon coinfection with the spleen focus-forming virus (SFFV). Both the low- and high-level F-MuLV infections generated CD8+ effector T cells that were essential for the control of viral replication. However, the low-level infection induced CD8+ T cells expressing solely FasL but not the cytotoxic molecules granzymes A and B, whereas the high level infection resulted in induction of CD8+ effector T cells secreting molecules of the granule exocytosis pathway. By using knockout mouse strains deficient in one or the other cytotoxic pathway, we found that low-level viral replication was controlled by CTL that expressed FasL but control of high-level viral replication required perforin and granzymes. Additional studies, in which F MuLV replication was enhanced experimentally in the absence of SFFV coinfection, supported the notion that only the replication level of F-MuLV was the critical factor that determined the differential expression of cytotoxic molecules by CD8+ T cells and the pathway of CTL cytotoxicity. PMID- 17728238 TI - Structure of adeno-associated virus serotype 8, a gene therapy vector. AB - Adeno-associated viruses (AAVs) are being developed as gene therapy vectors, and their efficacy could be improved by a detailed understanding of their viral capsid structures. AAV serotype 8 (AAV8) shows a significantly greater liver transduction efficiency than those of other serotypes, which has resulted in efforts to develop this virus as a gene therapy vector for hemophilia A and familial hypercholesterolemia. Pseudotyping studies show that the differential tissue tropism and transduction efficiencies exhibited by the AAVs result from differences in their capsid viral protein (VP) amino acids. Towards identifying the structural features underpinning these disparities, we report the crystal structure of the AAV8 viral capsid determined to 2.6-A resolution. The overall topology of its common overlapping VP is similar to that previously reported for the crystal structures of AAV2 and AAV4, with an eight-stranded beta-barrel and long loops between the beta-strands. The most significant structural differences between AAV8 and AAV2 (the best-characterized serotype) are located on the capsid surface at protrusions surrounding the two-, three-, and fivefold axes at residues reported to control transduction efficiency and antibody recognition for AAV2. In addition, a comparison of the AAV8 and AAV2 capsid surface amino acids showed a reduced distribution of basic charge for AAV8 at the mapped AAV2 heparin sulfate receptor binding region, consistent with an observed non-heparin-binding phenotype for AAV8. Thus, this AAV8 structure provides an additional platform for mutagenesis efforts to characterize AAV capsid regions responsible for differential cellular tropism, transduction, and antigenicity for these promising gene therapy vectors. PMID- 17728239 TI - Characterization of the early events in dengue virus cell entry by biochemical assays and single-virus tracking. AB - In this study, we investigated the cell entry characteristics of dengue virus (DENV) type 2 strain S1 on mosquito, BHK-15, and BS-C-1 cells. The concentration of virus particles measured by biochemical assays was found to be substantially higher than the number of infectious particles determined by infectivity assays, leading to an infectious unit-to-particle ratio of approximately 1:2,600 to 1:72,000, depending on the specific assays used. In order to explain this high ratio, we investigated the receptor binding and membrane fusion characteristics of single DENV particles in living cells using real-time fluorescence microscopy. For this purpose, DENV was labeled with the lipophilic fluorescent probe DiD (1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine, 4 chlorobenzenesulfonate salt). The surface density of the DiD dye in the viral membrane was sufficiently high to largely quench the fluorescence intensity but still allowed clear detection of single virus particles. Fusion of the viral membrane with the cell membrane was evident as fluorescence dequenching. It was observed that DENV binds very inefficiently to the cells used, explaining at least in part the high infectious unit-to-particle ratio. The particles that did bind to the cells showed different types of transport behavior leading to membrane fusion in both the periphery and perinuclear regions of the cell. Membrane fusion was observed in 1 out of 6 bound virus particles, indicating that a substantial fraction of the virus has the capacity to fuse. DiD dequenching was completely inhibited by ammonium chloride, demonstrating that fusion occurs exclusively from within acidic endosomes. PMID- 17728240 TI - Predominant mode of human immunodeficiency virus transfer between T cells is mediated by sustained Env-dependent neutralization-resistant virological synapses. AB - Cell-free human immunodeficiency virus type 1 (HIV-1) can initiate infections, but contact between infected and uninfected T cells can enhance viral spread through intercellular structures called virological synapses (VS). The relative contribution of VS to cell-free viral transfer has not been carefully measured. Using an ultrasensitive, fluorescent virus transfer assay, we estimate that when VS between HIV-expressing Jurkat T cells and primary CD4(+) T cells are formed, cell-associated transfer of virus is 18,000-fold more efficient than uptake of cell-free virus. Furthermore, in contrast to cell-free virus uptake, the VS deposits virus rapidly into focal, trypsin-resistant compartments in target T cells. This massive virus internalization requires Env-CD4 receptor interactions but is resistant to inhibition by patient-derived neutralizing antisera that inhibit homologous cell-free virus. Deleting the Env cytoplasmic tail does not abrogate VS-mediated transfer, but it renders the VS sensitive to neutralizing antibodies, suggesting that the tail limits exposure of VS-neutralizing epitopes on the surface of infected cells. Dynamic live imaging of the VS reveals that HIV expressing cells are polarized and make sustained, Env-dependent contacts with target cells through uropod-like structures. The polarized T-cell morphology, Env CD4 coordinated adhesion, and viral transfer from HIV-infected to uninfected cells suggest that VS allows HIV-1 to evade antibody neutralization and to disseminate efficiently. Future studies will discern to what extent this massive viral transfer contributes to productive infection or viral dissemination through the migration of virus-carrying T cells. PMID- 17728241 TI - Defining the mechanism of activation of AMP-activated protein kinase by the small molecule A-769662, a member of the thienopyridone family. AB - AMP-activated protein kinase (AMPK) plays a key role in maintaining energy homeostasis. Activation of AMPK in peripheral tissues has been shown to alleviate the symptoms of metabolic diseases, such as type 2 diabetes, and consequently AMPK is a target for treatment of these diseases. Recently, a small molecule activator (A-769662) of AMPK was identified that had beneficial effects on metabolism in ob/ob mice. Here we show that A-769662 activates AMPK both allosterically and by inhibiting dephosphorylation of AMPK on Thr-172, similar to the effects of AMP. A-769662 activates AMPK harboring a mutation in the gamma subunit that abolishes activation by AMP. An AMPK complex lacking the glycogen binding domain of the beta subunit abolishes the allosteric effect of A-769662 but not the allosteric activation by AMP. Moreover, mutation of serine 108 to alanine, an autophosphorylation site within the glycogen binding domain of the beta1 subunit, almost completely abolishes activation of AMPK by A-769662 in cells and in vitro, while only partially reducing activation by AMP. Based on our results we propose a model for activation of AMPK by A-769662. Importantly, this model may provide clues for understanding the mechanism by which AMP leads to activation of AMPK, which in turn may help in the identification of other AMPK activators. PMID- 17728243 TI - Towards covalent vaccination: improved polyclonal HIV neutralizing antibody response induced by an electrophilic gp120 V3 peptide analog. AB - Rare monoclonal antibodies (Abs) can form irreversible complexes with antigens by enzyme-like covalent nucleophile-electrophile pairing. To determine the feasibility of applying irreversible antigen inactivation by Abs as the basis of vaccination against microbes, we studied the polyclonal nucleophilic Ab response induced by the electrophilic analog of a synthetic peptide corresponding to the principal neutralizing determinant (PND) of human immunodeficiency virus type-1 (HIV) gp120 located in the V3 domain. Abs from mice immunized with the PND analog containing electrophilic phosphonates (E-PND) neutralized a homologous HIV strain (MN) approximately 50-fold more potently than control Abs from mice immunized with PND. The IgG fractions displayed binding to intact HIV particles. HIV complexes formed by anti-E-PND IgG dissociated noticeably more slowly than the complexes formed by anti-PND IgG. The slower dissociation kinetics are predicted to maintain long-lasting blockade of host cell receptor recognition by gp120. Pretreatment of the anti-PND IgG with a haptenic electrophilic phosphonate compound resulted in more rapid dissociation of the HIV-IgG complexes, consistent with the hypothesis that enhanced Ab nucleophilic reactivity induced by electrophilic immunization imparts irreversible character to the complexes. These results suggest that electrophilic immunization induces a sufficiently robust nucleophilic Ab response to enhance the anti-microbial efficacy of candidate polypeptide vaccines. PMID- 17728242 TI - Ubiquitin-dependent proteolytic control of SUMO conjugates. AB - Posttranslational protein modification with small ubiquitin-related modifier (SUMO) is an important regulatory mechanism implicated in many cellular processes, including several of biomedical relevance. We report that inhibition of the proteasome leads to accumulation of proteins that are simultaneously conjugated to both SUMO and ubiquitin in yeast and in human cells. A similar accumulation of such conjugates was detected in Saccharomyces cerevisiae ubc4 ubc5 cells as well as in mutants lacking two RING finger proteins, Ris1 and Hex3/Slx5-Slx8, that bind to SUMO as well as to the ubiquitin-conjugating enzyme Ubc4. In vitro, Hex3-Slx8 complexes promote Ubc4-dependent ubiquitylation. Together these data identify a previously unrecognized pathway that mediates the proteolytic down-regulation of sumoylated proteins. Formation of substrate-linked SUMO chains promotes targeting of SUMO-modified substrates for ubiquitin-mediated proteolysis. Genetic and biochemical evidence indicates that SUMO conjugation can ultimately lead to inactivation of sumoylated substrates by polysumoylation and/or ubiquitin-dependent degradation. Simultaneous inhibition of both mechanisms leads to severe phenotypic defects. PMID- 17728244 TI - Stimulation of c-Myc transcriptional activity by vIRF-3 of Kaposi sarcoma associated herpesvirus. AB - Kaposi sarcoma-associated herpesvirus is associated with two lymphoproliferative disorders, primary effusion lymphoma (PEL) and Castleman disease. In PEL, Kaposi sarcoma-associated herpesvirus is present in a latent form expressing only few viral genes. Among them is a viral homologue of cellular interferon regulatory factors, vIRF-3. To study the role of vIRF-3 in PEL lymphomagenesis, we analyzed the interaction of vIRF-3 with cellular proteins. Using yeast two-hybrid screen, we detected the association between vIRF-3 and c-Myc suppressor, MM-1alpha. The vIRF-3 and MM-1alpha interaction was also demonstrated by glutathione S transferase pulldown assay and coimmunoprecipitation of endogenous vIRF-3 and MM 1alpha in PEL-derived cell lines. Overexpression of vIRF-3 enhanced the c-Myc dependent transcription of the gene cdk4. Addressing the molecular mechanism of the vIRF-3-mediated stimulation, we demonstrated that the association between MM 1alpha and c-Myc was inhibited by vIRF-3. Furthermore, the recruitment of vIRF-3 to the cdk4 promoter and the elevated levels of the histone H3 acetylation suggest the direct involvement of vIRF-3 in the activation of c-Myc-mediated transcription. These findings indicate that vIRF-3 can effectively stimulate c Myc function in PEL cells and consequently contribute to de-regulation of B-cell growth and differentiation. PMID- 17728245 TI - Neural adrenergic/cyclic AMP regulation of the immunoglobulin E receptor alpha subunit expression in the mammalian pinealocyte: a neuroendocrine/immune response link? AB - The high affinity immunoglobulin E receptor (FcepsilonRI) complex is dedicated to immunoglobulin E-mediated allergic responses. Expression of the FcepsilonRI receptor is thought to be relatively stable and limited to mast cells, basophils, eosinophils, monocytes, Langerhans cells, platelets, and neutrophils. We now report that the FcepsilonRIalpha and FcepsilonRIgamma polypeptides are expressed in the pinealocyte, the melatonin-secreting cell of the pineal gland. Moreover, Fcer1a mRNA levels increased approximately 100-fold at night to levels that were higher than in other tissues examined. Pineal FcepsilonRIalpha protein also increased markedly at night from nearly undetectable daytime levels. Our studies indicate that pineal Fcer1a mRNA levels are controlled by a well described neural pathway that controls pineal function. This pathway includes the master circadian oscillator in the suprachiasmatic nucleus and passes through central and peripheral structures. The circadian expression of FcepsilonRIalpha in the pineal gland is driven by this neural circuit via an adrenergic/cyclic AMP mechanism. Pineal FcepsilonRIalpha and FcepsilonRIgamma may represent a previously unrealized molecular link between the neuroendocrine and immune systems. PMID- 17728246 TI - Signal responsiveness of IkappaB kinases is determined by Cdc37-assisted transient interaction with Hsp90. AB - The IkappaB kinase (IKK) holocomplex, containing the kinases IKKalpha, IKKbeta, and the scaffold NEMO (NF-kappaB essential modifier), mediates activation of NF kappaB by numerous physiological stimuli. Heat shock protein 90 (Hsp90) and the co-chaperone Cdc37 have been indicated as additional subunits, but their specific functions in signal transduction are indistinct. Using an RNA interference approach, we demonstrate that Cdc37 recruits Hsp90 to the IKK complex in a transitory manner, preferentially via IKKalpha. Binding is conferred by N terminal as well as C-terminal residues of Cdc37. Cdc37 is essential for the maturation of de novo synthesized IKKs into enzymatically competent kinases but not for assembly of an IKK holocomplex. Mature IKKs, T-loop-phosphorylated after stimulation either by receptor-mediated signaling or upon DNA damage, further require Hsp90-Cdc37 to generate an activated state. Thus, the present data denote Hsp90-Cdc37 as a transiently acting essential regulatory component of IKK signaling. PMID- 17728247 TI - Incorporation of newly synthesized fatty acids into cytosolic glycerolipids in pea leaves occurs via acyl editing. AB - In expanding pea leaves, over 95% of fatty acids (FA) synthesized in the plastid are exported for assembly of eukaryotic glycerolipids. It is often assumed that the major products of plastid FA synthesis (18:1 and 16:0) are first incorporated into 16:0/18:1 and 18:1/18:1 molecular species of phosphatidic acid (PA), which are then converted to phosphatidylcholine (PC), the major eukaryotic phospholipid and site of acyl desaturation. However, by labeling lipids of pea leaves with [(14)C]acetate, [(14)C]glycerol, and [(14)C]carbon dioxide, we demonstrate that acyl editing is an integral component of eukaryotic glycerolipid synthesis. First, no precursor-product relationship between PA and PC [(14)C]acyl chains was observed at very early time points. Second, analysis of PC molecular species at these early time points showed that >90% of newly synthesized [(14)C]18:1 and [(14)C]16:0 acyl groups were incorporated into PC alongside a previously synthesized unlabeled acyl group (18:2, 18:3, or 16:0). And third, [(14)C]glycerol labeling produced PC molecular species highly enriched with 18:2, 18:3, and 16:0 FA, and not 18:1, the major product of plastid fatty acid synthesis. In conclusion, we propose that most newly synthesized acyl groups are not immediately utilized for PA synthesis, but instead are incorporated directly into PC through an acyl editing mechanism that operates at both sn-1 and sn-2 positions. Additionally, the acyl groups removed by acyl editing are largely used for the net synthesis of PC through glycerol 3-phosphate acylation. PMID- 17728248 TI - Endoplasmic reticulum chaperones stabilize nicotinic receptor subunits and regulate receptor assembly. AB - We examined interactions between the endoplasmic reticulum (ER) chaperones calnexin (CN), ERp57, and immunological heavy chain-binding protein (BiP) and nicotinic acetylcholine receptor (nAChR) subunits. The three chaperones rapidly associate with newly synthesized nAChR subunits. Interactions between nAChR subunits and ERp57 occur via transient intermolecular disulfide bonds and do not require subunit N-linked glycosylation. The associations of ERp57 or CN with AChR subunits are long lived and prolong subunit lifetime approximately 10-fold. Coexpression of CN or ERp57 alone does not affect nAChR assembly or trafficking, but together they cause a significant decrease in nAChR expression and assembly. In contrast, associations with BiP are shorter lived and do not alter nAChR expression and assembly. However, a mutated BiP that slows its dissociation significantly increases its associations and decreases nAChR expression and assembly. Our results suggest that interactions with the chaperones regulate the levels of nAChRs assembled in the ER by stabilizing and sequestering subunits during assembly. PMID- 17728249 TI - Microbial products stimulate human Toll-like receptor 2 expression through histone modification surrounding a proximal NF-kappaB-binding site. AB - Previous studies have yielded conflicting results regarding the ability of microbial products to activate TLR2 gene expression in human monocytes. In this study, we found that TLR2 mRNA was rapidly up-regulated in human monocytes treated with TLR2 and TLR4 agonists, and this corresponded to an increase in cell surface receptor levels. This induction was abrogated by actinomycin D as well as a pharmacologic inhibitor of NF-kappaB, suggesting that the TLR2 gene is transcriptionally activated via NF-kappaB. Microbial agonists were found to shift the transcription initiation site of the TLR2 gene, and sequence examination revealed a near-consensus NF-kappaB-binding element immediately upstream of this site. Electromobility shift assays confirmed that NF-kappaB bound to this putative site in vitro. However, luciferase reporter plasmids driven by the TLR2 promoter were not responsive to TLR2 agonists. Overexpression of the NF-kappaB p65 subunit was sufficient to induce expression of the endogenous TLR2 mRNA, and co-transfection of the CREB-binding protein and p300 co-activators further increased TLR2 mRNA levels. Chromatin immunoprecipitation analysis revealed that p65, CREB-binding protein, and p300 are recruited to the TLR2 promoter upon stimulation of human monocytes followed by histone hyperacetylation. Taken together, these results define a mechanism whereby histone modification and increased promoter access induce expression of human TLR2 following infection. PMID- 17728250 TI - Stereospecific proton transfer by a mobile catalyst in mammalian fructose-1,6 bisphosphate aldolase. AB - Class I fructose-1,6-bisphosphate aldolases catalyze the interconversion between the enamine and iminium covalent enzymatic intermediates by stereospecific exchange of the pro(S) proton of the dihydroxyacetone-phosphate C3 carbon, an obligatory reaction step during substrate cleavage. To investigate the mechanism of stereospecific proton exchange, high resolution crystal structures of native and a mutant Lys(146) --> Met aldolase were solved in complex with dihydroxyacetone phosphate. The structural analysis revealed trapping of the enamine intermediate at Lys(229) in native aldolase. Mutation of conserved active site residue Lys(146) to Met drastically decreased activity and enabled trapping of the putative iminium intermediate in the crystal structure showing active site attachment by C-terminal residues 360-363. Attachment positions the conserved C terminal Tyr(363) hydroxyl within 2.9A of the C3 carbon in the iminium in an orientation consistent with incipient re face proton transfer. We propose a catalytic mechanism by which the mobile C-terminal Tyr(363) is activated by the iminium phosphate via a structurally conserved water molecule to yield a transient phenate, whose developing negative charge is stabilized by a Lys(146) positive charge, and which abstracts the C3 pro(S) proton forming the enamine. An identical C-terminal binding mode observed in the presence of phosphate in the native structure corroborates Tyr(363) interaction with Lys(146) and is consistent with transient C terminus binding in the enamine. The absence of charge stabilization and of a mobile C-terminal catalyst explains the extraordinary stability of enamine intermediates in transaldolases. PMID- 17728251 TI - Lactogens promote beta cell survival through JAK2/STAT5 activation and Bcl-XL upregulation. AB - One of the goals in the treatment for diabetes is to enhance pancreatic beta cell function, proliferation, and survival. This study explores the role of lactogenic hormones, prolactin (PRL) and placental lactogen (PL), in beta cell survival. We have previously shown that transgenic mice expressing mouse placental lactogen-1 (mPL1) in beta cells under the rat insulin II promoter (RIP) are resistant to the diabetogenic and cytotoxic effects of streptozotocin (STZ) in vivo. The current study demonstrates that lactogens protect rat insulinoma (INS-1) cells and primary mouse beta cells against two distinct beta cell death inducers, STZ and dexamethasone (DEX), in vitro. Further, we identify the mechanism through which lactogens protect beta cells against DEX-induced death. The signaling pathway mediating this protective effect is the janus-activated-kinase-2/signal transducer and activator of transcription-5 (JAK2/STAT5) pathway. This is demonstrated in INS-1 cells and primary mouse beta cells using three separate approaches, pharmacological inhibitors, JAK2-specific siRNAs and a dominant negative STAT5 mutant. Furthermore, lactogens specifically and significantly increase the anti-apoptotic protein Bcl-XL in insulinoma cells and mouse islets. Bcl-XL-specific siRNA significantly inhibits lactogen-mediated protection against DEX-induced beta cell death. We believe this is the first direct demonstration of lactogens mediating their protective effect through the JAK2/STAT5 pathway in the beta cell and through Bcl-XL in any cell type. PMID- 17728253 TI - Properties, regulation, and in vivo functions of a novel protein kinase D: Caenorhabditis elegans DKF-2 links diacylglycerol second messenger to the regulation of stress responses and life span. AB - Protein kinase D (PKD) isoforms are protein kinase C effectors in signaling cascades controlled by diacylglycerol (DAG). All PKDs are regulated by DAG/phorbol 12-myristate 13-acetate-binding C1 domains and an activation loop (A loop). To understand how PKD isoforms diversify DAG signaling networks, it is essential to determine redundant and novel properties of their regulatory domains, characterize factors controlling PKD gene expression, and discover their in vivo physiological roles. Studies on a novel PKD, Caenorhabditis elegans DKF-2 (D kinase family-2), addressed these topics. The C1b domain mediates phorbol 12 myristate 13-acetate-induced translocation and activation of DKF-2. However, when DAG is elevated, C1a and C1b contribute equally to targeting/activation of DKF-2. DKF-2 C1 domains do not inhibit catalytic activity; they mediate delivery of DKF 2 to a membrane where protein kinase C phosphorylates Ser(925) and Ser(929) in the A-loop. This potently stimulates DKF-2 catalytic activity. Phosphorylation of Ser(925) alone switches on 70% of maximal kinase activity. Persistent phosphorylation of Ser(929) tags DKF-2 for proteasomal degradation; Ser(P)(925) plays a minor role in DKF-2 degradation. GATA enhancer sequences govern DKF-2 expression in intestine in vivo. Adult life span increases 40% in animals lacking DKF-2. In thermally stressed wild type animals, the DAF-16 transcription factor is segregated from the nuclei of adult intestinal cells. In contrast, DAF-16 enters adult intestinal nuclei of DKF-2-deficient, thermally stressed animals, where it can trigger gene transcription that protects against various insults. The results suggest a mechanism for increased longevity and show that a PKD links DAG signals to regulation of stress responses and life span. PMID- 17728254 TI - Mps1 activation loop autophosphorylation enhances kinase activity. AB - The Mps1 protein kinase is required for proper assembly of the mitotic spindle, checkpoint signaling, and several other aspects of cell growth and differentiation. Mps1 regulation is mediated by cell cycle-dependent changes in transcription and protein level. There is also a strong correlation between hyperphosphorylated mitotic forms of Mps1 and increased kinase activity. We investigated the role that autophosphorylation plays in regulating human Mps1 (hMps1) protein kinase activity. Here we report that hyperphosphorylated hMps1 forms are not the only active forms of the kinase. However, autophosphorylation of hMps1 within the activation loop is required for full activity in vitro. Mass spectrometry analysis of de novo synthesized enzyme in Escherichia coli identified autophosphorylation sites at residues Thr(675), Thr(676), and Thr(686), but phosphatase-treated and reactivated enzyme was only phosphorylated on Thr(676). Mutation of Thr(676) in hMps1 or the corresponding Thr(591) residue within yeast Mps1 reduces kinase activity in vitro. We find that overexpression of an hMps1-T676A mutation inhibits centrosome duplication in RPE1 cells. Likewise, yeast cells harboring mps1-T591A as the sole MPS1 allele are not viable. Our data strongly support the conclusion that site-specific Mps1 autophosphorylation within the activation loop is required for full activity in vitro and function in vivo. PMID- 17728252 TI - Regulated proteolytic processing of Tie1 modulates ligand responsiveness of the receptor-tyrosine kinase Tie2. AB - Regulated ectodomain shedding followed by intramembrane proteolysis has recently been recognized as important in cell signaling and for degradation of several type I transmembrane proteins. The receptor-tyrosine kinase Tie1 is known to undergo ectodomain cleavage generating a membrane-tethered endodomain. Here we show Tie1 is a substrate for regulated intramembrane proteolysis. After Tie1 ectodomain cleavage the newly formed 45-kDa endodomain undergoes additional proteolytic processing mediated by gamma-secretase to generate an amino-terminal truncated 42-kDa fragment that is subsequently degraded by proteasomal activity. This sequential processing occurs constitutively and is stimulated by phorbol ester and vascular endothelial growth factor. To assess the biological significance of regulated Tie1 processing, we analyzed its effects on angiopoietin signaling. Activation of ectodomain cleavage causes loss of phosphorylated Tie1 holoreceptor and generation of phosphorylated receptor fragments in the presence of cartilage oligomeric protein angiopoietin 1. A key function of gamma-secretase is in preventing accumulation of these phosphorylated fragments. We also find that regulated Tie1 processing modulates ligand responsiveness of the Tie-1-associated receptor Tie2. Activation of Tie1 ectodomain cleavage increases cartilage oligomeric protein angiopoietin 1 activation of Tie2. This correlates with increased ability of Tie2 to bind ligand after shedding of the Tie1 extracellular domain. A similar enhancement of ligand activation of Tie2 is seen when Tie1 expression is suppressed by RNA interference. Together these data indicate that Tie1, via its extracellular domain, limits the ability of ligand to bind and activate Tie2. Furthermore the data suggest that regulated processing of Tie1 may be an important mechanism for controlling signaling by Tie2. PMID- 17728255 TI - Holliday junction processing activity of the BLM-Topo IIIalpha-BLAP75 complex. AB - BLM, the protein mutated in Bloom's syndrome, possesses a helicase activity that can dissociate DNA structures, including the Holliday junction, expected to arise during homologous recombination. BLM is stably associated with topoisomerase IIIalpha (Topo IIIalpha) and the BLAP75 protein. The BLM-Topo IIIalpha-BLAP75 (BTB) complex can efficiently resolve a DNA substrate that harbors two Holliday junctions (the double Holliday junction) in a non-crossover manner. Here we show that the Holliday junction unwinding activity of BLM is greatly enhanced as a result of its association with Topo IIIalpha and BLAP75. Enhancement of this BLM activity requires both Topo IIIalpha and BLAP75. Importantly, Topo IIIalpha cannot be substituted by Escherichia coli Top3, and the Holliday junction unwinding activity of BLM-related helicases WRN and RecQ is likewise impervious to Topo IIIalpha and BLAP75. However, the topoisomerase activity of Topo IIIalpha is dispensable for the enhancement of the DNA unwinding reaction. We have also ascertained the requirement for the BLM ATPase activity in double Holliday junction dissolution and DNA unwinding by constructing, purifying, and characterizing specific mutant variants that lack this activity. These results provide valuable information concerning how the functional integrity of the BTB complex is governed by specific protein-protein interactions among the components of this complex and the enzymatic activities of BLM and Topo IIIalpha. PMID- 17728256 TI - A calcium-gated lid and a large beta-roll sandwich are revealed by the crystal structure of extracellular lipase from Serratia marcescens. AB - Lipase LipA from Serratia marcescens is a 613-amino acid enzyme belonging to family I.3 of lipolytic enzymes that has an important biotechnological application in the production of a chiral precursor for the coronary vasodilator diltiazem. Like other family I.3 lipases, LipA is secreted by Gram-negative bacteria via a type I secretion system and possesses 13 copies of a calcium binding tandem repeat motif, GGXGXDXUX (U, hydrophobic amino acids), in the C terminal part of the polypeptide chain. The 1.8-A crystal structure of LipA reveals a close relation to eukaryotic lipases, whereas family I.1 and I.2 enzymes appear to be more distantly related. Interestingly, the structure shows for the N-terminal lipase domain a variation on the canonical alpha/beta hydrolase fold in an open conformation, where the putative lid helix is anchored by a Ca(2+) ion essential for activity. Another novel feature observed in this lipase structure is the presence of a helical hairpin additional to the putative lid helix that exposes a hydrophobic surface to the aqueous medium and might function as an additional lid. The tandem repeats form two separated parallel beta-roll domains that pack tightly against each other. Variations of the consensus sequence of the tandem repeats within the second beta-roll result in an asymmetric Ca(2+) binding on only one side of the roll. The analysis of the properties of the beta-roll domains suggests an intramolecular chaperone function. PMID- 17728258 TI - Human B-lymphocytes express alpha2-6-sialylated 6-sulfo-N-acetyllactosamine serving as a preferred ligand for CD22/Siglec-2. AB - CD22/Siglec-2, an important inhibitory co-receptor on B-lymphocytes, is known to recognize alpha2-6-sialylated glycan as a specific ligand. Here we propose that the alpha2-6-sialylated and 6-GlcNAc-sulfated determinant serves as a preferred ligand for CD22 because the binding of a human B-cell line to CD22 was almost completely abrogated after incubating the cells with NaClO3, an inhibitor of cellular sulfate metabolism, and was also significantly inhibited by a newly generated monoclonal antibody specific to the alpha2-6-sialylated 6-sulfo-N acetyllactosamine (LacNAc) determinant (KN343, murine IgM). The alpha2-6 sialylated 6-sulfo-LacNAc determinant defined by the antibody was significantly expressed on a majority of normal human peripheral B-lymphocytes as well as follicular B-lymphocytes in peripheral lymph nodes. The determinant was also expressed in endothelial cells of high endothelial venules of secondary lymphoid tissues, including lymph nodes, tonsils, and intestine-associated lymphoid tissues, more strongly than on B-lymphocytes, suggesting a role for CD22 in B cell interaction with blood vessels and trafficking. These results indicate that the alpha2-6-sialylated 6-sulfo-LacNAc determinant serves as an endogenous ligand for human CD22 and suggest the possibility that 6-GlcNAc sulfation as well as alpha2-6-sialylation may regulate CD22/Siglec-2 functions in humans. PMID- 17728257 TI - Crystal structure and mutagenesis of the metallochaperone MeaB: insight into the causes of methylmalonic aciduria. AB - MeaB is an auxiliary protein that plays a crucial role in the protection and assembly of the B(12)-dependent enzyme methylmalonyl-CoA mutase. Impairments in the human homologue of MeaB, MMAA, lead to methylmalonic aciduria, an inborn error of metabolism. To explore the role of this metallochaperone, its structure was solved in the nucleotide-free form, as well as in the presence of product, GDP. MeaB is a homodimer, with each subunit containing a central alpha/beta-core G domain that is typical of the GTPase family, as well as alpha-helical extensions at the N and C termini that are not found in other metalloenzyme chaperone GTPases. The C-terminal extension appears to be essential for nucleotide-independent dimerization, and the N-terminal region is implicated in protein-protein interaction with its partner protein, methylmalonyl-CoA mutase. The structure of MeaB confirms that it is a member of the G3E family of P-loop GTPases, which contains other putative metallochaperones HypB, CooC, and UreG. Interestingly, the so-called switch regions, responsible for signal transduction following GTP hydrolysis, are found at the dimer interface of MeaB instead of being positioned at the surface of the protein where its partner protein methylmalonyl-CoA mutase should bind. This observation suggests a large conformation change of MeaB must occur between the GDP- and GTP-bound forms of this protein. Because of their high sequence homology, the missense mutations in MMAA that result in methylmalonic aciduria have been mapped onto MeaB and, in conjunction with mutagenesis data, provide possible explanations for the pathology of this disease. PMID- 17728259 TI - Androgen receptor regulation of the versican gene through an androgen response element in the proximal promoter. AB - Versican, one of the key components of prostatic stroma, plays a central role in tumor initiation and progression. Here, we investigated promoter elements and mechanisms of androgen receptor (AR)-mediated regulation of the versican gene in prostate cancer cells. Using transient transfection assays in prostate cancer LNCaP and cervical cancer HeLa cells engineered to express the AR, we demonstrate that the synthetic androgen R1881 and dihydrotestosterone stimulate expression of a versican promoter-driven luciferase reporter vector (versican-Luc). Further, both basal and androgen-stimulated versican-Luc activities were significantly diminished in LNCaP cells, when AR gene expression was knocked down using a short hairpin RNA. Methylation-protection footprinting analysis revealed an AR protected element between positions +75 and +102 of the proximal versican promoter, which strongly resembled a consensus steroid receptor element. Electrophoretic mobility shift and supershift assays revealed strong and specific binding of the recombinant AR DNA binding domain to oligonucleotides corresponding to this protected DNA sequence. Site-directed mutagenesis of the steroid receptor element site markedly diminished R1881-stimulated versican-Luc activity. In contrast to the response seen using LNCaP cells, R1881 did not significantly induce versican promoter activity and mRNA levels in AR-positive prostate stromal fibroblasts. Interestingly, overexpression of beta-catenin in the presence of androgen augmented versican promoter activity 10- and 30-fold and enhanced versican mRNA levels 2.8-fold in fibroblasts. In conclusion, we demonstrate that AR transactivates versican expression, which may augment tumor stromal interactions and may contribute to prostate cancer progression. PMID- 17728260 TI - An ICD lead with a twist after visiting the gym! PMID- 17728261 TI - Anatomic relations of the Marshall vein: importance for catheterization of the coronary sinus in ablation procedures. AB - AIMS: Our objective was to study the anatomic relations of the human left atrial oblique vein (Marshall vein), particularly of its ostium opening into the coronary sinus, in order to guide ablation procedures related to that vein. METHODS AND RESULTS: The study was carried out in 23 heart-specimens (mean weight 446 +/- 204 g) of individuals whose mean ages were 43 +/- 21 years, 20 males. The coronary sinus was opened longitudinally, exposing the ostium of the tributary veins; the Vieussens valve was looked for, as well as its relationship to the left atrial oblique vein. The diameters of the left atrial oblique vein and the coronary sinus ostia were measured and the distance between them was determined. The left atrial oblique vein could be identified in 20 (87%) of the hearts, while the Vieussens valve was present in 17 (74%) of the specimens (in 16 of which the left atrial oblique vein was identified). In such condition, the vein was adjacent to the Vieussens valve and proximally positioned relative to the coronary sinus ostium in most of them (14/16 cases). The mean diameters of the left atrial oblique vein and of the coronary sinus ostia were, respectively, 1.23 +/- 0.38 and 8.22 +/- 1.88 mm. The mean distance between both ostia was 30.9 +/- 10.2 mm. CONCLUSION: When present, the left atrial oblique vein can be easily recognized, adjacent to the Vieussens valve. The mean distance between the coronary sinus opening and left atrial oblique vein ostium was around 30 mm, independently of the heart weight and the presence of cardiomegaly. PMID- 17728262 TI - Unusual patch-matrix organization in the retrosplenial cortex of the reeler mouse and Shaking rat Kawasaki. AB - The rat granular retrosplenial cortex (GRS) is a simplified cortex, with distinct stratification and, in the uppermost layers, distinct modularity. Thalamic and cortical inputs are segregated by layers and in layer 1 colocalize, respectively, with apical dendritic bundles originating from neurons in layers 2 or 5. To further investigate this organization, we turned to reelin-deficient reeler mouse and Shaking rat Kawasaki. We found that the disrupted lamination, evident in Nissl stains in these rodents, is in fact a patch-matrix mosaic of segregated afferents and dendrites. Patches consist of thalamocortical connections, visualized by vesicular glutamate transporter 2 (VGluT2) or AChE. The surrounding matrix consists of corticocortical terminations, visualized by VGluT1 or zinc. Dendrites concentrate in the matrix or patches, depending on whether they are OCAM positive (matrix) or negative (patches). In wild-type rodents and, presumably, mutants, OCAM(+) structures originate from layer 5 neurons. By double labeling for dendrites (filled by Lucifer yellow in fixed slice) and OCAM immunofluorescence, we ascertained 2 populations in reeler: dendritic branches either preferred (putative layer 5 neurons) or avoided (putative supragranular neurons) the OCAM(+) matrix. We conclude that input-target relationships are largely preserved in the mutant GRS and that dendrite-dendrite interactions involving OCAM influence the formation of the mosaic configuration. PMID- 17728263 TI - Decomposing the neural correlates of antisaccade eye movements using event related FMRI. AB - The antisaccade task is a model of the conflict between an unwanted reflexive response (which must be inhibited) and a complex volitional response (which must be generated). The present experiment aimed to investigate separately the neural correlates of these cognitive components using a delayed saccade paradigm to dissociate saccade inhibition from generation. Seventeen healthy volunteers completed event-related functional magnetic resonance imaging at 1.5 T during saccades to and away from a peripheral visual target (prosaccades and antisaccades, respectively). Saccades were requested in response to an auditory go signal on average 12 s after peripheral target appearance. It was found that the right supramarginal gyrus showed significantly greater activation during the inhibition phase than the generation phase of the paradigm for both antisaccade and prosaccade trials, suggesting a role in saccade inhibition or stimulus detection. On the other hand, the right lateral frontal eye field and bilateral intraparietal sulcus showed evidence of selective involvement in antisaccade generation. Ventrolateral and dorsolateral prefrontal cortices showed comparable levels of activation in both phases of the task. These areas likely fulfill a more general supervisory role in the volitional control of eye movements, such as stimulus appraisal, task set, and decision making. PMID- 17728264 TI - Action outcomes are represented in human inferior frontoparietal cortex. AB - The simple action of pressing a switch has many possible interpretations--the actor could be turning on a light, deleting critical files from a computer, or even turning off a life-support system. In each of these cases, the motor parameters of the action are the same but the physical outcome differs. We report evidence of suppressed responses in right inferior parietal and right inferior frontal cortex when participants saw repeated movies showing the same action outcome, but these regions did not distinguish the kinematic parameters by which the action was accomplished. Thus, these brain areas encode the physical outcomes of human actions in the world. These results are compatible with a hierarchical model of human action understanding in which a cascade of specialized processes from occipital to parietal and frontal regions allow humans to understand the physical consequences of actions in the world and the intentions underlying those actions. PMID- 17728265 TI - The orexins/hypocretins and schizophrenia. AB - Advances in molecular biology have led to new peptides and proteins being discovered on a regular basis, including the isolation of a number of neurotransmitter candidates. Rarely, however, do these immediately capture the attention of the scientific community. The isolation and characterization of the orexin/hypocretin peptides a decade ago resulted in a slew of studies that have helped clarified their diverse functions, including prominent roles in arousal and appetitive behavior. A number of recent studies have detailed the role of the orexins/hypocretins in attention and cognition and uncovered an involvement in schizophrenia and the mechanisms of action of antipsychotic drugs (APDs). This issue of Schizophrenia Bulletin presents several articles that review our current understanding and point to future directions for the study of the orexins/hypocretins in schizophrenia and APD actions. PMID- 17728268 TI - Re: "Multiparameter calibration of a natural history model of cervical cancer". PMID- 17728266 TI - Patterns of structural MRI abnormalities in deficit and nondeficit schizophrenia. AB - Negative symptoms of schizophrenia have generally been found in association with ventricular enlargement and prefrontal abnormalities. These relationships, however, have not been observed consistently, most probably because negative symptoms are heterogeneous and result from different pathophysiological mechanisms. The concept of deficit schizophrenia (DS) was introduced by Carpenter et al to identify a clinically homogeneous subgroup of patients characterized by the presence of primary and enduring negative symptoms. Findings of brain structural abnormalities reported by magnetic resonance imaging (MRI) studies focusing on DS have been mixed. The present study included 34 patients with DS, 32 with nondeficit schizophrenia (NDS), and 31 healthy comparison subjects, providing the largest set of MRI findings in DS published so far. The Schedule for the Deficit Syndrome was used to categorize patients as DS or NDS patients. The 2 patient groups were matched on age and gender and did not differ on clinical variables, except for higher scores on the negative dimension and more impaired interpersonal relationships in DS than in NDS subjects. Lateral ventricles were larger in NDS than in control subjects but were not enlarged in patients with DS. The cingulate gyri volume was smaller in NDS but not in DS patients as compared with healthy subjects. Both groups had smaller dorsolateral prefrontal cortex and temporal lobes than healthy subjects, but DS patients had significantly less right temporal lobe volume as compared with NDS patients. These findings do not support the hypothesis that DS is the extreme end of a severity continuum within schizophrenia. PMID- 17728269 TI - When epidemiology meets the Internet: Web-based surveys in the Millennium Cohort Study. AB - Almost 60% of American households were connected to the Internet in 2001, when the Millennium Cohort Study, the largest longitudinal study ever undertaken by the Department of Defense, was launched. To facilitate survey completion, increase data integrity, and encourage cohort retention while maintaining the highest standards of participant privacy, an online questionnaire was made available on the World Wide Web in addition to a traditional paper questionnaire sent via US mail. Over 50% of 77,047 participants chose to enroll in the study via the Web, affording substantial cost savings to the project. Using multivariable logistic regression, the authors compared the demographic and health characteristics of Web responders with those of paper responders. Web responders were slightly more likely to be male, to be younger, to have a high school diploma or college degree, and to work in information technology or another technical occupation. Web responders were more likely to be obese and to smoke more cigarettes and were less likely to be problem alcohol drinkers and to report occupational exposures. Question completion rates were 98.3%, on average, for both Web and paper responders. Web responders provided more complete contact information, including their e-mail addresses. These results demonstrate the value of survey research conducted over the Internet in concert with traditional mail survey strategies. PMID- 17728270 TI - Coronary artery calcification in Japanese men in Japan and Hawaii. AB - Explanations for the low prevalence of atherosclerosis in Japan versus the United States are often confounded with genetic variation. To help remove such confounding, the authors compared coronary artery calcification (CAC), a marker of subclinical atherosclerosis, between Japanese men in Japan and Japanese men in Hawaii. Findings were based on risk factors and CAC measured from 2001 to 2005 in 311 men in Japan and 300 men in Hawaii. Men were aged 40-50 years and without cardiovascular disease. After age adjustment, there was a threefold excess in the odds of prevalent CAC scores of > or = 10 in Hawaii versus Japan (relative odds = 3.2, 95% confidence interval: 2.1, 4.9). Whereas men in Hawaii had a generally poorer risk factor profile, men in Japan were four times more likely to smoke cigarettes (49.5% vs. 12.7%, p < 0.001). In spite of marked risk factor differences between the samples, none of the risk factors explained the low amounts of CAC in Japan. After risk factor adjustment, the relative odds of CAC scores of > or = 10 in Hawaii versus Japan was 4.0 (95% confidence interval: 2.2, 7.4). Further studies are needed to identify factors that protect against atherosclerosis in Japanese men in Japan. PMID- 17728271 TI - Particulate air pollution and mortality in the United States: did the risks change from 1987 to 2000? AB - Evaluation of the public health impact of air quality regulations, referred to as accountability research, is increasingly viewed as a necessary component of responsible governmental policy interventions. The authors present an example of accountability assessment based on evaluating change in the short-term effect of airborne particles over a period of increasingly stringent regulation that might have changed the chemical composition and toxicity of these particles. They used updated data and methods of the National Morbidity Mortality Air Pollution Study to estimate national average relative rates of the effects of particulate matter or =240 MYA). Phylogenetic analyses of C terminal sequences grouped all mygalomorph spidroins, except Aliatypus fibroin 1, in a clade. Aliatypus fibroin 1 was instead more closely related to a subset of araneomorph spidroins, including those used in prey wrapping. Our results suggest that spidroin paralogs existed prior to the divergence of mygalomorphs and araneomorphs, followed by a far greater expansion of this gene family in araneomorphs, paralleling the dramatic functional diversification of their silk gland anatomy. PMID- 17728282 TI - Identification and characterization of several dietary alkaloids as weak inhibitors of hedgehog signaling. AB - The Hedgehog (Hh) signaling pathway plays an integral role in the patterning and development of diverse structures in the vertebrate embryo. Aberrations in Hh signaling are associated with a range of developmental defects including failure of interhemispheric division of the embryonic forebrain as well as midline facial dysmorphia including cleft lip/palate and cyclopia, collectively termed holoprosencephaly (HPE). Postnatally, Hh signaling has been postulated to play a pivotal role in healing and repair processes and inappropriate Hh pathway activation has been implicated in several types of cancers. The Veratrum alkaloid cyclopamine is a potent inhibitor of Hh signaling and causes HPE-like defects in diverse species including sheep, hamster, mouse, and zebra fish. Using murine cell-based assays, we have determined that a number of dietary alkaloids similar in structure to cyclopamine also inhibit Hh signaling but with significantly lower potency. We found that these dietary compounds act additively through a mechanism similar to cyclopamine, downstream of Ptc1 and upstream of Gli1. Using an embryonic zebra fish developmental assay, we found that while cyclopamine exposure caused HPE-like defects, exposure to one of these dietary compounds, solanidine, did not. PMID- 17728283 TI - Elemental selenium at nano size (Nano-Se) as a potential chemopreventive agent with reduced risk of selenium toxicity: comparison with se-methylselenocysteine in mice. AB - Selenium (Se) is an essential trace element with a narrow margin between beneficial and toxic effects. As a promising chemopreventive agent, its use requires consumption over the long term, so the toxicity of Se is always a crucial concern. Based on clinical findings and recent studies in selenoprotein gene-modified mice, it is likely that the antioxidant function of one or more selenoproteins is responsible for the chemopreventive effect of Se. Furthermore, upregulation of phase 2 enzymes by Se has been implicated as a possible chemopreventive mechanism at supranutritional dietary levels. Se methylselenocysteine (SeMSC), a naturally occurring organic Se product, is considered as one of the most effective chemopreventive selenocompounds. The present study revealed that, as compared with SeMSC, elemental Se at nano size (Nano-Se) possessed equal efficacy in increasing the activities of glutathione peroxidase, thioredoxin reductase, and glutathione S-transferase, but had much lower toxicity as indicated by median lethal dose, acute liver injury, survival rate, and short-term toxicity. Our results suggest that Nano-Se can serve as a potential chemopreventive agent with reduced risk of Se toxicity. PMID- 17728284 TI - Cadmium-induced germline apoptosis in Caenorhabditis elegans: the roles of HUS1, p53, and MAPK signaling pathways. AB - The transition metal cadmium (Cd) has been shown to induce apoptosis in a variety of cell lines and tissues. Caspase activation of the tumor suppressor gene p53 and mitogen-activated protein kinase (MAPK) signaling cascades have been reported to be involved in Cd-induced apoptosis. However, the underlying pathways of Cd induced apoptosis have not been clearly elucidated in the in vivo systems, primarily for the lack of appropriate animal models. The nematode Caenorhabditis elegans has been shown to be a good model to study basic biological processes, including apoptosis. In this study, we used the mutated alleles of C. elegans homologs of known mammalian genes that are involved in regulation of apoptosis. Sublethal doses of Cd exposure increased C. elegans germline apoptosis in a dose- and time-dependent manner. The loss-of-function mutations of DNA damage response (DDR) genes HUS1 and p53 exhibited significant increase in germline apoptosis under Cd exposure, and the depletion of p53 antagonist ABL1 significantly enhanced apoptosis. Cd-induced apoptosis was blocked in the loss-of-function alleles of both c-Jun N-terminal kinase (JNK) and p38 MAPK cascades, which behaved normally under gamma-irradiation. Our findings implicate that both JNK and p38 MAPK cascades participate in Cd-induced apoptosis. Together, the results of this study suggest the nonessential roles of the DDR genes hus1 and p53 in Cd induced germline apoptosis and that the apoptosis occurs through the ASK1/2-MKK7 JNK and ASK1/2-MKK3/6-p38 signaling pathways in a caspase-dependent manner. Finally, our study demonstrates that C. elegans is a mammalian in vivo substitute model to study the mechanisms of Cd-induced apoptosis. PMID- 17728285 TI - Effects of altered food intake during pubertal development in male and female wistar rats. AB - The U.S. Environmental Protection Agency is currently validating assays that will be used in a Tier I Screening Battery to detect endocrine disrupting chemicals. A primary concern with the Protocols for the Assessment of Pubertal Development and Thyroid Function in Juvenile Male and Female Rats is that a nonspecific reduction in body weight (BWT) during the exposure period may potentially confound the interpretation of effects on the endocrine endpoints. Wistar rats were underfed 10, 20, 30, or 40% less than the ad libitum food consumed by controls from postnatal days (PNDs) 22 to 42 (females) or PNDs 23 to 53 (males). Terminal BWT of females and males were 2, 4, 12, and 19% and 2, 6, 9, and 19% lower than controls, respectively. In the females, neither the age of pubertal onset nor any of the thyroid hormone endpoints were affected by food restriction (FR) that led to a 12% decrease in BWT. Similarly, none of the male reproductive endpoints examined were altered by FR that led to a 9% BWT decrease. However, decreased triiodothyronine and thyroxin was observed in FR males with a 9% reduced BWT. While these data support the use of the maximum tolerated dose for BWT (10%) for the female protocol, effects on the male thyroid endpoints indicate that a slightly lower limit (40 years). HLA-DRB1*07, in linkage disequilibrium with HLA-Cw*06, was also associated with patients with PsA having type I psoriasis (OR 2.7, 95% CI 2.1, 3.7, p<0.00001). HLA-DRB1*04 alleles and the SE were associated with undifferentiated inflammatory arthritis but not with PsA. CONCLUSIONS: The SE is not a PsA susceptibility locus. HLA-Cw*06 and HLA-DRB1*07 are associated with patients with PsA having type I psoriasis, suggesting that the primary association is with age of onset of psoriasis. Patients with PsA having type I psoriasis, therefore, have a genetic background different to those with type II psoriasis, and adjustment for this is necessary in future studies that investigate the genetic susceptibility of PsA. PMID- 17728336 TI - Genome dissection of traits related to domestication in azuki bean (Vigna angularis) and comparison with other warm-season legumes. AB - BACKGROUND: The objective of this study was to dissect into quantitative trait loci (QTLs) the large morphological and physiological differences between cultivated azuki bean (Vigna angularis) and a wild relative and to infer the commonalities of the QTLs for domestication-related traits across the Asian Vigna and with other warm-season legumes. METHODS: Two linkage maps, for the BC(1)F(1) and F(2) populations, respectively, from the same cross between azuki bean and V. nepalensis were developed. Using these linkage maps QTLs for 33 domestication related traits were analysed and mapped. The location of mapped QTLs was compared with locations of similar QTLs in other warm-season legumes. KEY RESULTS: QTLs were detected for seed-, pod-, stem- and leaf-related traits. Most traits were controlled by between two and nine QTLs but several traits, such as pod dehiscence, were controlled by single genes. QTLs for domestication-related traits were restricted to particular regions of the azuki bean genome, especially linkage groups 1, 2, 4, 7 and 9. Linkage groups 1 and 2 had QTLs for a suite of traits including pod size, germination, seed size and lower stem length. QTLs on linkage groups 7 and 9 were associated with upper stem length, maximum leaf size and pod and seed size. Pleiotropy or close linkage of genes for domestication related traits is suggested in these regions. While some QTLs are common to azuki bean and other warm-season legumes, many are recorded for the first time in azuki bean. CONCLUSIONS: QTLs for a large number of domestication-related traits have been mapped for the first time in azuki bean. QTLs with unexpected effect and new QTLs for traits such as seed size have been found. The results provide a foundation that will be useful for improvement of azuki bean and related legumes. PMID- 17728337 TI - Guadua zuloagae sp. nov., the first petrified bamboo culm record from the Ituzaingo Formation (Pliocene), Parana basin, Argentina. AB - BACKGROUND AND AIMS: The anatomical characterization and morphology of Guadua zuloagae nov. sp. (Poaceae-Bambusoideae) culm was determined. This material was collected at the Toma Vieja fossil locality, Parana basin, Argentina. This fossil culm is the first record of Bambusoideae in sediments of the Pliocene from the Ituzaingo Formation. The studied specimen was compared with the taxa of the Bambusoideae sub-family, especially with the American woody bamboos and others taxa that have woody culms, including Arundo, Thysalonaena and Gynerium. METHODS: The material was preserved by siliceous cellular permineralization, and it was prepared for microscopic examination by surface polishing and thin sections. The morphology and anatomy of this new species were described. The estimated height, critical buckling height and safety factor were calculated on the basis of the fossil bamboo diameter using the formula of Niklas. The relationship and comparison with the nearest living relatives (NLRs) are discussed. KEY RESULTS: Well-preserved petrified culm with internodes and nodes from the Pliocene of Argentina provides the basis for the description of a new fossil bamboo, Guadua zuloagae. The results of the anatomical analysis of the fossil bamboo showed a great affinity with the extant species Guadua angustifolia and constitute the first evidence of petrified bamboo culm. CONCLUSIONS: The new fossil bamboo culm constitutes the only fossil record, preserved as permineralized by silicification, in the world. This fossil record indicates that the genus Guadua was more widespread in the past than today. Discovery of G. zuloagae allows the presence of a Bambusoideae understorey in the mixed forests described for the Ituzaingo Formation to be inferred. The climatic conditions inferred from fossil bamboo and sedimentary deposits indicate a temperate-warm, humid climate. PMID- 17728338 TI - Relationship between shoot-rooting and root-sprouting abilities and the carbohydrate and nitrogen reserves of Mediterranean dwarf shrubs. AB - BACKGROUND AND AIMS: This study analysed the differences in nitrogen (N), non structural carbohydrates (NSC) and biomass allocation to the roots and shoots of 18 species of Mediterranean dwarf shrubs with different shoot-rooting and resprouting abilities. Root N and NSC concentrations of strict root-sprouters and species resprouting from the base of the stems were also compared. METHODS: Soluble sugars (SS), starch and N concentrations were assessed in roots and shoots. The root : shoot ratio of each species was obtained by thorough root excavations. Cross-species analyses were complemented by phylogenetically independent contrasts (PICs). KEY RESULTS: Shoot-rooting species showed a preferential allocation of starch to shoots rather than roots as compared with non-shoot-rooting species. Resprouters displayed greater starch concentrations than non-sprouters in both shoots and roots. Trends were maintained after PICs analyses, but differences became weak when root-sprouters versus non-root sprouters were compared. Within resprouters, strict root-sprouters showed greater root concentrations and a preferential allocation of starch to the roots than stem-sprouters. No differences were found in the root : shoot ratio of species with different rooting and resprouting abilities. CONCLUSIONS: The shoot-rooting ability of Mediterranean dwarf shrubs seems to depend on the preferential allocation of starch and SS to shoots, though alternative C-sources such as current photosynthates may also be involved. In contrast to plants from other mediterranean areas of the world, the resprouting ability of Mediterranean dwarf shrubs is not related to a preferential allocation of N, NSC and biomass to roots. PMID- 17728339 TI - High-order interactions among genetic polymorphisms in nucleotide excision repair pathway genes and smoking in modulating bladder cancer risk. AB - Polymorphisms in nucleotide excision repair (NER) genes may cause variations in DNA repair capacity and increase susceptibility to bladder cancer through complex gene-gene and gene-smoking interactions. We applied two data mining approaches to explore high-order gene-gene and gene-environment interactions among 13 polymorphisms in nine major NER genes in 696 bladder cancer patients and 629 controls. Individually, only the XPD D312N variant genotypes exhibited a slightly increased risk for bladder cancer. In classification and regression tree analysis, we observed gene-gene interactions among CCNH V270A, ERCC6 M1097V and RAD23B A249V in ever smokers: smokers with the variant alleles at these three loci had an almost 30-fold increased risk of bladder cancer [odds ratio (OR): 29.6, 95% confidence interval (CI): 9.3-93.7]. When evaluating combined effect of above four single nucleotide polymorphisms, we found a significant gene dosage effect for increased bladder cancer risk with increasing numbers of unfavorable genotypes. Compared with individuals with less than 2 unfavorable genotypes, those with 2 unfavorable genotypes and more than 2 unfavorable genotypes exhibited increased bladder cancer risk with ORs of 1.14 (95% CI: 0.87-1.51) and 2.15 (95% CI: 1.56-2.97), respectively (P < 0.001). The risks were more evident in ever smokers with ORs of 1.43 (95% CI: 1.02-2.01) and 3.40 (95% CI: 2.24 5.15), respectively (P < 0.001). In multifactor dimensionality reduction (MDR) analysis, the five-factor model including smoking, CCNH V270A, ERCC6 M1097V, RAD23B A249V and XPD D312N had the best ability to predict bladder cancer risk. The contributions of these polymorphisms may jointly affect bladder cancer risk through gene-gene and gene-smoking interactions. PMID- 17728340 TI - Relative prevalence of different sexually transmitted infections in HIV discordant sexual partnerships: data from a risk network study in a high-risk New York neighbourhood. AB - OBJECTIVES: To determine infection patterns of sexually transmitted infections that facilitate HIV transmission among HIV-discordant couples. METHODS: 112 initial respondents were recruited in an impoverished neighbourhood of Brooklyn, New York. Their sexual (and injection) partners were recruited in up to four additional network sampling waves for a final sample of 465 persons aged 18 years or older. After separate informed consent had been obtained, blood and urine were collected and tested for HIV, type-specific antibodies to herpes simplex virus (HSV-2), syphilis, chlamydia and gonorrhoea. RESULTS: Of 30 HIV-discordant partnerships, five were same-sex male partnerships and 25 were opposite-sex partnerships. No subjects tested positive for syphilis or gonorrhoea. Two couples were chlamydia-discordant. For HSV-2, 16 couples were double-positive, eight discordant, four double-negative, and two comprised a HSV-2-negative with a partner with missing herpes data. CONCLUSIONS: HSV-2 was present in 83% of the HIV-discordant couples, chlamydia in 7%, and syphilis and gonorrhoea in none. HSV 2 is probably more important for HIV transmission than bacterial sexually transmitted diseases because it is more widespread. Even given the limited generalisability of this community-based sample, there seems to be an important HIV-prevention role for herpes detection and prevention activities in places where HIV-infected people are likely to be encountered, including sexually transmitted disease clinics, HIV counselling and testing programmes, prisons, needle exchanges, and drug abuse treatment programmes. The effects of HSV suppressive therapy in highly impacted groups should also be investigated. PMID- 17728342 TI - SOX3 activity during pharyngeal segmentation is required for craniofacial morphogenesis. AB - Craniofacial development is a complex multi-step process leading to the morphogenesis of the face and sense organs, and to that of the neck, including the anteriormost part of the respiratory and digestive apparatus and associated endocrine glands. In vertebrates, the process is initiated by the formation of the pharyngeal arches from ectoderm, endoderm and mesoderm. These arches are then populated by neural crest cells, which originate from the central nervous system. We show here that, in mouse, there is a requirement for the HMG box factor SOX3 during the earliest stage of pharyngeal development: the formation of the pharyngeal pouches that segment the pharyngeal region by individualising each arch. In Sox3-null mutants, these pouches are expanded at the detriment of the second pharyngeal arch. As a consequence, neural crest cell migration and ectoderm-derived epibranchial placode development are affected, leading to craniofacial defects. We also show that Sox3 genetically interacts both with FgfR1 and with Sox2, another member of the Soxb1 family, to fulfil its function in the pharyngeal region. Although the importance of the neural crest has long been recognised, our studies highlight the equally crucial role of the pharyngeal region in craniofacial morphogenesis. They also give insight into the formation of pharyngeal pouches, of which little is known in vertebrates. Finally, this work introduces two new players in craniofacial development - SOX3 and SOX2. PMID- 17728341 TI - Current progress in network research: toward reference networks for key model organisms. AB - The collection of multiple genome-scale datasets is now routine, and the frontier of research in systems biology has shifted accordingly. Rather than clustering a single dataset to produce a static map of functional modules, the focus today is on data integration, network alignment, interactive visualization and ontological markup. Because of the intrinsic noisiness of high-throughput measurements, statistical methods have been central to this effort. In this review, we briefly survey available datasets in functional genomics, review methods for data integration and network alignment, and describe recent work on using network models to guide experimental validation. We explain how the integration and validation steps spring from a Bayesian description of network uncertainty, and conclude by describing an important near-term milestone for systems biology: the construction of a set of rich reference networks for key model organisms. PMID- 17728343 TI - Post-transcriptional repression of the Drosophila midkine and pleiotrophin homolog miple by HOW is essential for correct mesoderm spreading. AB - The even spreading of mesoderm cells in the Drosophila embryo is essential for its proper patterning by ectodermally derived signals. In how germline clone embryos, defects in mesoderm spreading lead to a partial loss of dorsal mesoderm derivatives. HOW is an RNA-binding protein that is thought to regulate diverse mRNA targets. To identify direct HOW targets, we implemented a series of selection methods on mRNAs whose levels were elevated in how germline clone embryos during the stage of mesoderm spreading. Four mRNAs were found to be specifically elevated in the mesoderm of how germline clone embryos, and to exhibit specific binding to HOW via their 3' UTRs. Importantly, overexpression of three of these genes phenocopied the mesoderm-spreading phenotype of how germline clone embryos. Further analysis showed that overexpressing one of these genes, miple (a Drosophila midkine and pleiotrophin heparin-binding growth factor), in the mesoderm led to abnormal scattered MAPK activation, a phenotype that might explain the abnormal mesoderm spreading. In addition, the number of EVE-positive cells, which are responsive to receptor tyrosine kinase (RTK) signaling, was increased following Miple overexpression in the mesoderm and appeared to be dependent on Heartless function. In summary, our analysis suggests that HOW downregulates the levels of a number of mRNA species in the mesoderm in order to enable proper mesoderm spreading during early embryogenesis. PMID- 17728344 TI - A regulatory network involving Foxn4, Mash1 and delta-like 4/Notch1 generates V2a and V2b spinal interneurons from a common progenitor pool. AB - In the developing central nervous system, cellular diversity depends in part on organising signals that establish regionally restricted progenitor domains, each of which produces distinct types of differentiated neurons. However, the mechanisms of neuronal subtype specification within each progenitor domain remain poorly understood. The p2 progenitor domain in the ventral spinal cord gives rise to two interneuron (IN) subtypes, V2a and V2b, which integrate into local neuronal networks that control motor activity and locomotion. Foxn4, a forkhead transcription factor, is expressed in the common progenitors of V2a and V2b INs and is required directly for V2b but not for V2a development. We show here in experiments conducted using mouse and chick that Foxn4 induces expression of delta-like 4 (Dll4) and Mash1 (Ascl1). Dll4 then signals through Notch1 to subdivide the p2 progenitor pool. Foxn4, Mash1 and activated Notch1 trigger the genetic cascade leading to V2b INs, whereas the complementary set of progenitors, without active Notch1, generates V2a INs. Thus, Foxn4 plays a dual role in V2 IN development: (1) by initiating Notch-Delta signalling, it introduces the asymmetry required for development of V2a and V2b INs from their common progenitors; (2) it simultaneously activates the V2b genetic programme. PMID- 17728345 TI - The testis-specific proteasome subunit Prosalpha6T of D. melanogaster is required for individualization and nuclear maturation during spermatogenesis. AB - Most regulated proteolysis in eukaryotes is carried out by the 26S proteasome. This large, multisubunit complex comprises a catalytic core particle (20S proteasome) and a regulatory particle (19S regulator) capping each end. In Drosophila, about a third of the 32 proteasome subunits are found to have testis specific isoforms, encoded by paralogous genes. Here, we characterize in detail the spermatogenic expression of the core particle subunit Prosalpha6 (Pros35) and its testis-specific isoform Prosalpha6T. Using GFP-tagged transgenes, it is shown that whereas the Prosalpha6 subunit is expressed in early stages of spermatogenesis, gradually fading away following meiosis, the testis-specific Prosalpha6T becomes prominent in spermatid nuclei and cytoplasm after meiosis, and persists in mature sperm. In addition, these subunits are found in numerous ;speckles' near individualization complexes, similar to the previously described expression pattern of the caspase Dronc (Nedd2-like caspase), suggesting a link to the apoptosis pathway. We also studied the phenotypes of a loss-of-function mutant of Prosalpha6T generated by targeted homologous recombination. Homozygous males are sterile and show spermatogenic defects in sperm individualization and nuclear maturation, consistent with the expression pattern of Prosalpha6T. The results demonstrate a functional role of testis-specific proteasomes during Drosophila spermatogenesis. PMID- 17728346 TI - Inactivation of serine protease Matriptase1a by its inhibitor Hai1 is required for epithelial integrity of the zebrafish epidermis. AB - Epithelial integrity requires the adhesion of cells to each other as well as to an underlying basement membrane. The modulation of adherence properties is crucial to morphogenesis and wound healing, and deregulated adhesion has been implicated in skin diseases and cancer metastasis. Here, we describe zebrafish that are mutant in the serine protease inhibitor Hai1a (Spint1la), which display disrupted epidermal integrity. These defects are further enhanced upon combined loss of hai1a and its paralog hai1b. By applying in vivo imaging, we demonstrate that Hai1-deficient keratinocytes acquire mesenchymal-like characteristics, lose contact with each other, and become mobile and more susceptible to apoptosis. In addition, inflammation of the mutant skin is evident, although not causative of the epidermal defects. Only later, the epidermis exhibits enhanced cell proliferation. The defects of hai1 mutants can be phenocopied by overexpression and can be fully rescued by simultaneous inactivation of the serine protease Matriptase1a (St14a), indicating that Hai1 promotes epithelial integrity by inhibiting Matriptase1a. By contrast, Hepatocyte growth factor (Hgf), a well known promoter of epithelial-mesenchymal transitions and a prime target of Matriptase1 activity, plays no major role. Our work provides direct genetic evidence for antagonistic in vivo roles of Hai1 and Matriptase1a to regulate skin homeostasis and remodeling. PMID- 17728347 TI - The first bromodomain of Brdt, a testis-specific member of the BET sub-family of double-bromodomain-containing proteins, is essential for male germ cell differentiation. AB - Brdt is a testis-specific member of the distinctive BET sub-family of bromodomain motif-containing proteins, a motif that binds acetylated lysines and is implicated in chromatin remodeling. Its expression is restricted to the germ line, specifically to pachytene and diplotene spermatocytes and early spermatids. Targeted mutagenesis was used to generate mice carrying a mutant allele of Brdt, Brdt(Delta)(BD1), which lacks only the first of the two bromodomains that uniquely characterize BET proteins. Homozygous Brdt(Delta)(BD1/)(Delta)(BD1) mice were viable but males were sterile, producing fewer and morphologically abnormal sperm. Aberrant morphogenesis was first detected in step 9 elongating spermatids, and those elongated spermatids that were formed lacked the distinctive foci of heterochromatin at the peri-nuclear envelope. Quantitative reverse transcription (RT)-PCR showed threefold increased levels of histone H1t (Hist1h1t) in Brdt(Delta)(BD1/)(Delta)(BD1) testes and chromatin immunoprecipitation revealed that Brdt protein, but not Brdt(DeltaBD1) protein, was associated with the promoter of H1t. Intracytoplasmic sperm injection suggested that the DNA in the Brdt(Delta)(BD1) mutant sperm could support early embryonic development and yield functional embryonic stem cells. This is the first demonstration that deletion of just one of the two bromodomains in members of the BET sub-family of bromodomain containing proteins has profound effects on in vivo differentiation. PMID- 17728349 TI - Bone morphogenetic proteins specify the retinal pigment epithelium in the chick embryo. AB - In vertebrates, the neuroepithelium of the optic vesicle is initially multipotential, co-expressing a number of transcription factors that are involved in retinal pigment epithelium (RPE) and neural retina (NR) development. Subsequently, extrinsic signals emanating from the surrounding tissues induce the separation of the optic vesicle into three domains: the optic stalk/nerve, the NR and the RPE. Here, we show that bone morphogenetic proteins (BMPs) are sufficient and essential for RPE development in vivo. Bmp4 and Bmp7 are expressed in the surface ectoderm overlying the optic vesicle, the surrounding mesenchyme and/or presumptive RPE during the initial stages of eye development. During the initial stages of chick eye development the microphthalmia-associated transcription factor (Mitf), important for RPE development, is expressed in the optic primordium that is covered by the BMP-expressing surface ectoderm. Following BMP application, the optic neuroepithelium, including the presumptive optic stalk/nerve and NR domain, develop into RPE as assessed by the expression of Otx2, Mitf, Wnt2b and the pigmented cell marker MMP115. By contrast, interfering with BMP signalling prevents RPE development in the outer layer of the optic cup and induces NR-specific gene expression (e.g. Chx10). Our results show that BMPs are sufficient and essential for RPE development during optic vesicle stages. We propose a model in which the BMP-expressing surface ectoderm initiates RPE specification by inducing Mitf expression in the underlying neuroepithelium of the optic vesicle. PMID- 17728348 TI - Molecularly and temporally separable lineages form the hindbrain roof plate and contribute differentially to the choroid plexus. AB - Both hindbrain roof plate epithelium (hRPe) and hindbrain choroid plexus epithelium (hCPe) produce morphogens and growth factors essential for proper hindbrain development. Despite their importance, little is known about how these essential structures develop. Recent genetic fate maps indicate that hRPe and hCPe descend from the same pool of dorsal neuroectodermal progenitor cells of the rhombic lip. A linear developmental progression has been assumed, with the rhombic lip producing non-mitotic hRPe, and seemingly uniform hRPe transforming into hCPe. Here, we show that hRPe is not uniform but rather comprises three spatiotemporal fields, which differ in organization, proliferative state, order of emergence from the rhombic lip, and molecular profile of either the constituent hRPe cells themselves and/or their parental progenitors. Only two fields contribute to hCPe. We also present evidence for an hCPe contribution directly by the rhombic lip at late embryonic stages when hRPe is no longer present; indeed, the production interval for hCPe by the rhombic lip is surprisingly extensive. Further, we show that the hCPe lineage appears to be unique among the varied rhombic lip-derived lineages in its proliferative response to constitutively active Notch1 signaling. Collectively, these findings provide a new platform for investigating hRPe and hCPe as neural organizing centers and provide support for the model that they are themselves patterned structures that might be capable of influencing neural development along multiple spatial and temporal axes. PMID- 17728350 TI - Sequential and combinatorial inputs from Nodal, Delta2/Notch and FGF/MEK/ERK signalling pathways establish a grid-like organisation of distinct cell identities in the ascidian neural plate. AB - The ascidian neural plate has a grid-like organisation, with six rows and eight columns of aligned cells, generated by a series of stereotypical cell divisions. We have defined unique molecular signatures for each of the eight cells in the posterior-most two rows of the neural plate - rows I and II. Using a combination of morpholino gene knockdown, dominant-negative forms and pharmacological inhibitors, we tested the role of three signalling pathways in defining these distinct cell identities. Nodal signalling at the 64-cell stage was found to be required to define two different neural plate domains - medial and lateral - with Nodal inducing lateral and repressing medial identities. Delta2, an early Nodal target, was found to then subdivide each of the lateral and medial domains to generate four columns. Finally, a separate signalling system along the anteroposterior axis, involving restricted ERK1/2 activation, was found to promote row I fates and repress row II fates. Our results reveal how the sequential integration of three signalling pathways - Nodal, Delta2/Notch and FGF/MEK/ERK - defines eight different sub-domains that characterise the ascidian caudal neural plate. Most remarkably, the distinct fates of the eight neural precursors are each determined by a unique combination of inputs from these three signalling pathways. PMID- 17728351 TI - Functions of the novel RhoGAP proteins RGA-3 and RGA-4 in the germ line and in the early embryo of C. elegans. AB - We have identified two redundant GTPase activating proteins (GAPs) - RGA-3 and RGA-4 - that regulate Rho GTPase function at the plasma membrane in early Caenorhabditis elegans embryos. Knockdown of both RhoGAPs resulted in extensive membrane ruffling, furrowing and pronounced pseudo-cleavages. In addition, the non-muscle myosin NMY-2 and RHO-1 accumulated on the cortex at sites of ruffling. RGA-3 and RGA-4 are GAPs for RHO-1, but most probably not for CDC-42, because only RHO-1 was epistatic to the two GAPs, and the GAPs had no obvious influence on CDC-42 function. Furthermore, knockdown of either the RHO-1 effector, LET-502, or the exchange factor for RHO-1, ECT-2, alleviated the membrane-ruffling phenotype caused by simultaneous knockdown of both RGA-3 and RGA-4 [rga-3/4 (RNAi)]. GFP::PAR-6 and GFP::PAR-2 were localized at the anterior and posterior part of the early C. elegans embryo, respectively showing that rga-3/4 (RNAi) did not interfere with polarity establishment. Most importantly, upon simultaneous knockdown of RGA-3, RGA-4 and the third RhoGAP present in the early embryo, CYK 4, NMY-2 spread over the entire cortex and GFP::PAR-2 localization at the posterior cortex was greatly diminished. These results indicate that the functions of CYK-4 are temporally and spatially distinct from RGA-3 and RGA-4 (RGA-3/4). RGA-3/4 and CYK-4 also play different roles in controlling LET-502 activation in the germ line, because rga-3/4 (RNAi), but not cyk-4 (RNAi), aggravated the let-502(sb106) phenotype. We propose that RGA-3/4 and CYK-4 control with which effector molecules RHO-1 interacts at particular sites at the cortex in the zygote and in the germ line. PMID- 17728352 TI - Increased frequency of reproductive health problems among fathers of boys with hypospadias. AB - BACKGROUND: Some studies have suggested an association between paternal subfertility and hypospadias among their sons, although the association has not been systematically investigated. We therefore compared male reproductive health among a group of fathers of boys with hypospadias and a group of fathers to normal children. METHODS: A total of 64 fathers of boys with hypospadias participated; 349 partners of pregnant women served as a control group. All men delivered a semen sample, had a blood sample drawn, underwent a physical examination and completed a questionnaire. RESULTS: Fathers of boys with hypospadias had a significantly lower median sperm concentration (54.1 x 10(6)/ml) (P = 0.004) and total sperm count (222.0 x 10(6)) (P = 0.009) than the controls (81.2 and 326.0 x 10(6)/ml). In addition, the fathers of boys with hypospadias more often reported to have had disorders in the urogenital system (hypospadias, cryptorchidism and testicular cancer) (11/64) (P < 0.001) than the control group (16/349). No significant differences in waiting time to pregnancy was observed, however, 15% of fathers to boys with hypospadias had received fertility treatment. CONCLUSIONS: Fathers of boys with hypospadias not only have an increased frequency of hypospadias, but also decreased semen quality. Most likely fathers and sons share the same susceptibility genes for reproductive dysfunction, but additional impact of environmental factors cannot be excluded. PMID- 17728353 TI - Class I histone deacetylase expression in the human cyclic endometrium and endometrial adenocarcinomas. AB - BACKGROUND: Class I histone deacetylases (HDACs) and acetylases (HATs) are members of transcriptional pre-initiation complexes assembled by steroid hormone receptors. Recently, HDAC inhibitors were shown to enhance differentiation of endometrial fibroblasts and endometrial adenocarcinomas. However, there is only rare information on HDAC and HAT expression in the human endometrium. METHODS: HDAC-1, -2, -3 and HAT (PCAF and GCN5) mRNA expression was studied in tissue from premenopausal women undergoing hysterectomy by real-time or semiquantitative RT PCR. HDAC protein expression was assessed by Western Blot and immunohistochemistry. In endometrial adenocarcinomas (n = 17), HDAC-1 expression was studied by immunohistochemistry. RESULTS: In the human endometrium, HDAC-1, 2, -3 and PCAF mRNA are expressed without cyclical changes. Western blot analysis demonstrated that HDAC-2 protein expression was slightly, but significantly elevated in the secretory phase (P < 0.01 versus day 5-8), whereas HDAC-1 and -3 protein expression was constitutive throughout the menstrual cycle. By immunohistochemistry, nuclear expression of HDAC proteins was detected in all endometrial cell types. In the case of HDAC-3, immunostaining was significantly reduced in the endometrial surface epithelium on day 6-10 (P < 0.01 versus days 15-18 and 24-28). Compared to normal endometrium, a high proportion of endometrial adenocarcinomas showed impaired HDAC-1 protein expression in the epithelial and stromal compartment. CONCLUSIONS: Class I HDACs and HATs are expressed in the human endometrium throughout the menstrual cycle, suggesting the cyclic endometrium as a potential target for HDAC inhibitors. We hypothesis that alterations of HDAC and/or HAT expression are potentially involved in impaired endometrial differentiation. PMID- 17728354 TI - ESHRE Task Force on Ethics and Law 13: the welfare of the child in medically assisted reproduction. AB - The analysis of the welfare of the child in the context of medically assisted reproduction is divided in two parts: the first part addresses the risks associated with the would-be parent(s), the second part focuses on possible risks inherent in the technologies and treatments themselves. The risk factors connected with the intended parents may be medical and psychosocial. Two important considerations are raised here: the necessity to avoid discrimination and respect for the privacy of the patients. The second part concerns the ethical questions involved in the rapid dissemination of new technologies in assisted conception. Technology and research must always be subordinate to the welfare of the future offspring. The different steps involved in the responsible application of medical technologies to treat infertility are analysed. PMID- 17728356 TI - Vanishing twins: a predictor of small-for-gestational age in IVF singletons. AB - BACKGROUND: The purpose of this study was to assess the effect of a vanishing twin on the risk of being small-for-gestational age (SGA) in in vitro fertilization (IVF) singletons. METHODS: The study included 642 survivors of a vanished co-twin, 5237 primary singletons and 3678 primary twins. The survivor cohort was subdivided according to gestational age at the time of vanishing to give groups of early (<8 weeks), intermediate (8-22 weeks) and late (>22 weeks) survivors. RESULTS: The rate of SGA infants was significantly higher in survivors than in singletons (OR: 1.50, 95%CI: 1.03-2.20) and a significant inverse correlation was observed between SGA and the gestational age at the time of vanishing (r = -0.10, P < 0.02). Also in term infants, the risk of birthweight <2500 g was higher in survivors than in singletons (OR: 1.71, 95%CI: 1.06-2.74). A similar increase in the rate of low birthweight in term survivors was seen with increasing gestational age at the time of vanishing (r = -0.12; P < 0.01). In multiple logistic regression analysis adjusting for maternal age, parity, child gender and pre-eclampsia, the vanishing of a co-twin (OR: 1.56, 95%CI: 1.06-2.27) and gestational age at the time of vanishing (OR: 2.08, 95%CI: 1.00-4.35) were the only significant predictors of being SGA. CONCLUSIONS: IVF singletons with a vanished co-twin had a higher rate of SGA than singletons from a single gestation and the risk of SGA is increased with increasing gestational age at the time of vanishing. PMID- 17728357 TI - Exploring recombinant human erythropoietin in chronic progressive multiple sclerosis. AB - The neurodegenerative aspects of chronic progressive multiple sclerosis (MS) have received increasing attention in recent years, since anti-inflammatory and immunosuppressive treatment strategies have largely failed. However, successful neuroprotection and/or neuroregeneration in MS have not been demonstrated yet. Encouraged by the multifaceted neuroprotective effects of recombinant human erythropoietin (rhEPO) in experimental models, we performed an investigator driven, exploratory open label study (phase I/IIa) in patients with chronic progressive MS. Main study objectives were (i) evaluating safety of long-term high-dose intravenous rhEPO treatment in MS, and (ii) collecting first evidence of potential efficacy on clinical outcome parameters. Eight MS patients, five randomly assigned to high-dose (48,000 IU), three to low-dose (8000 IU) rhEPO treatment, and, as disease controls, two drug-naive Parkinson patients (receiving 48,000 IU) were followed over up to 48 weeks: A 6-week lead-in phase, a 12-week treatment phase with weekly EPO, another 12-week treatment phase with bi-weekly EPO, and a 24-week post-treatment phase. Clinical and electrophysiological improvement of motor function, reflected by a reduction in expanded disability status scale (EDSS), and of cognitive performance was found upon high-dose EPO treatment in MS patients, persisting for three to six months after cessation of EPO application. In contrast, low-dose EPO MS patients and drug-naive Parkinson patients did not improve in any of the parameters tested. There were no adverse events, no safety concerns and a surprisingly low need of blood-lettings. This first pilot study demonstrates the necessity and feasibility of controlled trials using high-dose rhEPO in chronic progressive MS. PMID- 17728358 TI - Expression of FGF-2 in neural progenitor cells enhances their potential for cellular brain repair in the rodent cortex. AB - Strategies to enhance the capacity of grafted stem/progenitors cells to generate multipotential, proliferative and migrating pools of cells in the postnatal brain could be crucial for structural repair after brain damage. We investigated whether the over-expression of basic fibroblast growth factor 2 (FGF-2) in neural progenitor cells (NPCs) could provide a robust source of migrating NPCs for tissue repair in the rat cerebral cortex. Using live imaging we provide direct evidence that FGF-2 over-expression significantly enhances the migratory capacity of grafted NPCs in complex 3D structures, such as cortical slices. Furthermore, we show that the migratory as well as proliferative properties of FGF-2 over expressing NPCs are maintained after in vivo transplantation. Importantly, after transplantation into a neonatal ischaemic cortex, FGF-2 over-expressing NPCs efficiently invade the injured cortex and generate an increased pool of immature neurons available for brain repair. Differentiation of progenitor cells into immature neurons was correlated with a gradual down-regulation of the FGF-2 transgene. These results reveal an important role for FGF-2 in regulating NPCs functions when interacting with the host tissue and offer a potential strategy to generate a robust source of migrating and immature progenitors for repairing a neonatal ischaemic cortex. PMID- 17728359 TI - Impaired tuning of a fast occipito-temporal response for print in dyslexic children learning to read. AB - Developmental dyslexia is defined as a disorder of learning to read. It is thus critical to examine the neural processes that impair learning to read during the early phase of reading acquisition, before compensatory mechanisms are adapted by older readers with dyslexia. Using electroencephalography-based event-related imaging, we investigated how tuning of visual activity for print advances in the same children before and after initial reading training in school. The focus was on a fast, coarse form of visual tuning for print, measured as an increase of the occipito-temporal N1 response at 150-270 ms in the event-related potential (ERP) to words compared to symbol strings. The results demonstrate that the initial development of reading skills and visual tuning for print progressed more slowly in those children who became dyslexic than in their control peers. Print-specific tuning in 2nd grade strongly distinguished dyslexic children from controls. It was maximal in the inferior occipito-temporal cortex, left-lateralized in controls, and reduced in dyslexic children. The results suggest that delayed initial visual tuning for print critically contributes to the development of dyslexia. PMID- 17728361 TI - BAFF, a newcomer to the lupus party. PMID- 17728360 TI - Distinct regional atrophy in the corpus callosum of patients with temporal lobe epilepsy. AB - We analysed the influence of mesial temporal lobe epilepsy on the thickness of the corpus callosum (CC) in a large sample of well-characterized patients (n = 96) and healthy controls (n = 28). In particular, we investigated whether callosal structures are differentially affected depending on the affected hemisphere and age of epilepsy onset. Overall, we observed that epilepsy is associated with a decreased thickness in posterior callosal regions. Patients with an early onset, especially patients with left onset, additionally exhibited a smaller callosal thickness in more anterior and midbody regions. These findings may reflect non-specific as well as specific effects of temporal lobe epilepsy on CC development and interhemispheric connectivity. PMID- 17728362 TI - Adherence with advice and prescriptions in SLE is mostly good, but better follow up is needed: a study with a questionnaire. AB - The objective was to evaluate the efficacy of the information policy given to all systemic lupus erythematosus (SLE) patients. One hundred consecutive SLE patients were asked to answer anonymously a questionnaire covering demographic issues including education, adherence with prescriptions and advice given and methods of sourcing information. Seventy-three females and ten males responded. The demographic data showed that 34 had a university education, 29 high school and 19 primary school education. An inability to work due to disease was increased compared with the matched population (P < 0.001). Forty-two reported that they had received advice about physical training and forty of them followed this advice. Only 28 out of 46 smokers reported that they had got any advice about smoking, and out of these only 13 followed the advice. The patients with university background were less likely to smoke (P < 0.05) and followed the advice more often (P < 0.05). Most patients followed given advice about exposure to sunlight. Thirty-five percent of those prescribed glucocorticoids reported that they varied from the prescribed dosages without consultation with their specialist. This behaviour was more common in the university group (P < 0.05), this grouping also had a higher median dosage. Seventy-three patients had read the booklet about SLE provided by the clinic. Accessing internet information was more common for those with university education (P < 0.01). This study shows that on the whole SLE patients follow given advice, but adherence varies. Aside from the issue of glucocorticoid dosage adherence, educational level seems to be the most important predictor for adherence to advice. Thus, we conclude that a more individualized approach to delivery of information is required and better follow up is needed. PMID- 17728363 TI - Induction therapies for class IV lupus nephritis with non-inflammatory necrotizing vasculopathy: mycophenolate mofetil or intravenous cyclophosphamide. AB - The presence of renal noninflammatory necrotizing vasculopathy (NNV) is often associated with a severe form of lupus nephritis (LN), which is unresponsive to standard therapy. We conducted a 6-month randomized, prospective, open-label trial comparing mycophenolate mofetil (MMF) (1.5-2.0 g/day) with monthly i.v. cyclophosphamide (CTX) (0.75-1.0 g/m2) as induction therapy for class IV LN with NNV. The primary and second end points were complete remission (CR) and partial remission (PR), respectively. Of 20 patients recruited, nine were randomly assigned to MMF and 11 to CTX. The baseline characteristics between groups were not significant. CR was achieved in four patients (44.4%) receiving MMF and in none of the patients receiving CTX (P = 0.026). PR was achieved in two patients (22.2%) in the MMF group and three patients (27.2%) in the CTX group. The total remission rate (CR + PR) in the MMF and CTX group was 66.6 and 27.2%, respectively (P = 0.17). MMF was more effective than i.v. CTX in reducing proteinuria and haematuria. Adverse events were significantly less frequent with MMF than with CTX (P = 0.028). MMF was superior to i.v. CTX in inducing CR of LN with NNV and had a more favourable safety profile. PMID- 17728364 TI - Oral health and the masticatory system in juvenile systemic lupus erythematosus. AB - Our objectives were to evaluate the oral health and the masticatory system of 48 juvenile systemic lupus erythematosus (JSLE) patients and to compare them with 48 healthy children and adolescents. Demographic data, clinical manifestations and therapies of JSLE were reviewed. The DMFT index (DMFTI), the plaque (PI) and the gingival bleeding (GI) indices, dental relationship, facial profile, clinical dysfunction and mandibular mobility indices were evaluated. The two groups were homogeneous regarding age, gender, Brazilian social-economic class and dental decay index (P > 0.05). Of note, the medians of the PI and the GI were higher in JSLE patients than in controls (61.5 versus 38.10, P = 0.003 and 26.0 versus 15.95, P = 0.014; respectively). Likewise, a linear statistical correlation was evidenced between the JSLE duration and the GI (P = 0.017, r = 0.11), cumulative dose of prednisone and the PI (P = 0.01, r = 0.385) and cumulative dose of prednisone and the GI ( P = 0.001, r = 0.471). The clinical dysfunction and mandibular mobility indices were higher in JSLE patients versus controls (P = 0.002, P = 0.025). Moreover, the median of the mandibular mobility index was higher in JSLE patients who used at least one immunosuppressive than on those who did not use this medication (P = 0.0001). These results suggest that JSLE patients had an inadequate oral hygiene, higher incidence of gingivitis and temporomandibular joint dysfunction. PMID- 17728365 TI - Peripheral vascular disease in systemic lupus erythematosus. AB - With increasing longevity of lupus patients, peripheral vascular disease (PVD) has become an important cause of morbidity. With no systematic study of PVD in systemic lupus erythematosus (SLE), this study was undertaken to define the frequency and spectrum of PVD in SLE and factors affecting such an occurrence. All medium-sized peripheral arteries of bilateral upper and lower extremities were studied in 50 SLE patients using Doppler ultrasonography. PVD was defined clinically as one or more of intermittent claudication, absent/unequal pulses, gangrene or ischemic ulcers and sub-clinically as asymptomatic patients with Doppler abnormalities, with > or =50% reduction in diameter considered hemodynamically significant. Mean (SD) age of the patients was 31.6 (10.1) years. Forty-one percent were hypertensive. Dyslipidemia was found in 62%. Fifteen (30%) had Raynaud's phenomenon. Fourteen (28%) patients had PVD, of whom three had positive markers for antiphospholipid antibody (aPL) and six were asymptomatic. Ischemic ulcers were seen in eight (16%), gangrene in three (6%), femoral artery plaques in two (4%), stenosis in four (8%) and intermittent claudication in none. Dyslipidemia was found to independently affect occurrence of PVD (OR = 5.37, [95% CI 1.05-27.5], P = 0.05). The causes of PVD overlap significantly and further studies are needed to ascertain the relative contribution of each. PMID- 17728366 TI - Hypertension and Afro-descendant ethnicity: a bad interaction for lupus nephritis treated with cyclophosphamide? AB - Hypertension and ethnicity are important prognostic factors in evolution of lupus nephritis. A cohort of 75 patients with lupus nephritis treated with cyclophosphamide was conducted to investigate the evolution of creatinine levels between Caucasians and Afro-descendants. A multiple linear model was used to evaluate the combined effects of ethnicity and hypertension over delta creatinine controlling confounders. Sample characteristics were: 85% females; mean (+/-SD) age of 33.6 +/- 12.0 years; 77% Caucasians; 40% hypertensive at renal biopsy; 91% WHO class IV; mean basal creatinine: 1.5 +/- 1.3 mg/dL; mean final creatinine: 2.1 +/- 2.5 mg/dL; 40% anaemia; proteinuria: 5.4 +/- 4.8 g/day. Comparing Caucasians and Afro-descendants, it was found: 28.1% versus 72.2% for hypertension (P = 0.002); 31.6% versus 66.7% for anaemia (P = 0.018); 5.9 +/- 5.0 versus 3.8 +/- 4.0. g/day (P = 0.02) for proteinuria. Other comparisons including basal creatinine did not reach statistical significance. Comparing outcomes between Caucasians and Afro-descendants, it was found: 10.5% versus 22.2% for doubling of creatinine (P = 0.24); 0.41 +/- 2.03 versus 1.05 +/- 2.41 for delta creatinine ( P = 0.29); 8.8% versus 22.2% for haemodialysis (P = 0.21) and 3.5% versus 5.6% for death (P = 0.99). Analysing delta creatinine with multiple linear regression showed that hypertension had a significant overall effect (b = 0.80; SE = 0.32; P = 0.015), ethnicity alone was not significant (b = 0.35; SE = 0.29; P = 0.228); however, the effect of hypertension on delta creatinine was more intense among Afro-descendants than among Caucasians (interaction term b = - 0.83; SE = 0.37; P = 0.027). Afro-descendants lupus patients experience worst prognosis of renal function probably due to the effect of hypertension and not ethnicity per se. PMID- 17728367 TI - Clinical manifestations and coronary artery disease risk factors at diagnosis of systemic lupus erythematosus: data from an international inception cohort. AB - Systemic Lupus International Collaborating Clinics (SLICC) comprises 27 centres from 11 countries. An inception cohort of 918 SLE patients has been assembled according to a standardized protocol between 2000 and 2006. Clinical features, classic coronary artery disease (CAD) risk factors, as well as other potential risk factors were collected. Of the 918 patients 89% were females, and of multi racial origin. Less than half the patients were living in a permanent relationship, 58% had post secondary education and 51% were employed. Eight percent had family history of SLE. At enrolment, with at mean age of diagnosis of 34.5 years, a significant number of patients already had CAD risk factors, such as hypertension (33%) and hypercholesterolemia (36%). Only 15% of the patients were postmenopausal, 16% were current smokers and 3.6% had diabetes at entry to the SLICC-RAS (Registry for Atherosclerosis). A number of patients in this multi racial, multi-ethnic inception cohort of lupus patients have classic CAD risk factors within a mean of 5.4 months from diagnosis. This cohort will be increased to 1500 patients to be followed yearly for 10 years. This will provide a unique opportunity to evaluate risk factors for accelerated atherosclerosis in SLE. PMID- 17728368 TI - Prevalence of endometriosis in women with systemic lupus erythematosus and Sjogren's syndrome. AB - Endometriosis is associated with a number of immunologic alterations. It has been suggested that autoimmune disorders could be more frequent in patients with endometriosis. The aim of this study is to ascertain whether the prevalence of two well-known autoimmune diseases [systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS)] is increased in women with endometriosis. The clinical charts of four different populations assisted at the same hospital were manually revised: (i) SLE population (n = 120), (ii) SS (n = 22), (iii) endometriosis (n = 342) and (iv) control population (n = 501 consecutive unselected asymptomatic women). Among SLE women, the prevalence of endometriosis was 1.67% (2/120), similar to the 4.39% prevalence of the control group (22/501), the OR being 0.37 [95%CI 0.09-1.59]. Among SS women, the prevalence of endometriosis was 9.09 (2/22), also similar to the control group OR 2.17 [95%CI 0.48-9.90]. In the same way, when comparing endometriosis cases with asymptomatic women, similar frequencies of SLE (0.58% and 0.2%) and SS were found (0% and 0%). Women with endometriosis do not have an increased prevalence of SLE or SS. PMID- 17728369 TI - Toxic epidermal necrolysis-like acute cutaneous lupus erythematosus. AB - The term "Acute Syndrome of Apoptotic Pan-Epidermolysis" (ASAP) designs clinical entities characterized by massive cleavage of the epidermis resulting from hyperacute epidermal basal cell apoptotic injury. It can be seen typically in classic toxic epidermal necrolysis (TEN), but occasionally occurs in non-drug induced entities called "TEN-like" diseases (e.g., lupus erythematosus (LE), acute graft versus host disease and pseudoporphyria). We would like to highlight the difficulties of establishing differential diagnoses between "TEN-like" LE and drug reactions, especially when LE has not been previously diagnosed. We report a patient with fulminate pattern of epidermal cell injury resulting in a clinical presentation having combined features of drug-induced TEN and acute cutaneous LE with laboratory findings of systemic LE (SLE) and without systemic symptoms or high-risk drug ingestion. Although most cases of ASAP in the setting of LE are drug-induced TEN, there are reported cases of "TEN-like" LE with subacute progression, absence of systemic involvement and lack of drug ingestion. Such cases usually have a previous history of SLE and positive serologic markers. Although some authors observed that these lesions could be related to systemic severity of SLE, this is the first patient reported who progresses to discoid LE and we think it could be a marker of good prognosis. PMID- 17728370 TI - Swallowing disturbance due to isolated vagus nerve involvement in systemic lupus erythematosus. AB - Neuropsychiatric lupus is a well-recognized complication of systemic lupus erythematosus (SLE) and encompasses a wide variety of neurological manifestations. Although isolated cranial nerve involvement is rare, it can cause significant morbidity and disability. This report describes a case with isolated vagus nerve involvement as the principal sign of central nervous system involvement. A 30-year-old female with SLE had one short course of lupus associated psychosis in December 2001. In August 2002, the patient suffered from progressive swallowing difficulty, developed a transient episode of hypercapnic respiratory failure and required nasogastric tube feeding due to isolated vagus nerve involvement. Magnetic resonance imaging revealed a subtle but distinct brainstem lesion over the ponto-medullary junction, near the location of the vagus nerve nuclei. The patient completely recovered three weeks later following treatment with intravenous dexamethasone. This report also discusses the differential diagnosis of this rare condition. PMID- 17728371 TI - A study of association of the complement C4 mutations with systemic lupus erythematosus in the Malaysian population. AB - The aim of the present study was to investigate the association of C4 gene mutations with systemic lupus erythematosus, in 130 Malaysian SLE patients and 130 healthy controls. Generally, various PCR approaches were used to screen the mutations of the C4 genes, which included 2 bp (+TC) insertions at codon 1213 in exon 29, 1 bp deletions (-C) at codon 811 in exon 20, 1 bp (-C), 2 bp (-GT) deletions at codons 522 and 497 in exon 13 and null alleles. No mutations located at exons 13, 20 and 29 of the C4 gene, were detected amongst the patient and control samples in this study. C4A*Q0 was found in two out of the 130 control samples, while C4B*Q0 was present in two out of the 130 SLE patients. Overall, our results do not demonstrate a significant association to these known C4 mutations identified by previous studies, in the Malaysian scenario. PMID- 17728372 TI - Systemic lupus erythematosus and infections: a retrospective study in Saudis. AB - This study demonstrates demographic, clinical and laboratory characteristics with special reference to infections in Saudi patients with SLE. One-hundred and ninety-nine patients with SLE treated at Riyadh Armed Forces Hospital, Saudi Arabia over a period of 15 years (1990-2005) were retrospectively reviewed. There were 162 females and 37 males (4.4 : 1) with an average age of 35 years at onset of disease. Duration of diseases ranged from one to 23 years with a mean of 7.23 years. Some of the clinical characteristics of SLE patients observed were nephritis (53.7%), fever (53.26%), neuropsychological disorder (36.18%), malar/butterfly rash (27.6%), pulmonary disorder (22.6%), photosensitivity (21.6%), cardiac involvement (21.1%) and oral ulcers (19.09%). Infection was the major complication with 58.79% of SLE patient having suffered from various infections. A total of 22 species of pathogens including gram positive and gram negative bacteria, viruses and fungi were isolated from 117 SLE patients. Single to multiple episode of infection with various pathogens were recorded however, majority of patients harboured one or two species of pathogens. Bacterial infection was predominant (78.6%) followed by viral (28.2%) and fungal (28.2%) infections. Forty-four percent of SLE patients were found to be infected with organisms classified as opportunistic. The high incidence of infections in SLE patients may be attributed to the multiple intrinsic and extrinsic risk factors including deficiency of complement (C3 and C4), disease activity, renal impairment, use of glucocorticoid and cytotoxic drugs. It is concluded that more judicious use of corticosteroids and other immunosuppressive agents will be critical to limit the infections in SLE and a high alert and close monitoring of patients will ensure optimal patient outcome, both in terms of morbidity and mortality. PMID- 17728373 TI - Infliximab-induced SLE-like syndrome involving the lung and pleura. PMID- 17728374 TI - Autonomic dysfunction in autoimmune diseases: consequence or cause? PMID- 17728375 TI - Increased hepatic CD36 expression contributes to dyslipidemia associated with diet-induced obesity. AB - OBJECTIVE: The etiology of type 2 diabetes often involves diet-induced obesity (DIO), which is associated with elevated plasma fatty acids and lipoprotein associated triglycerides. Since aberrant hepatic fatty acid uptake may contribute to this, we investigated whether increased expression of a fatty acid transport protein (CD36) in the liver during DIO contributes to the dyslipidemia that precedes development of type 2 diabetes. RESEARCH DESIGN AND METHODS: We determined the effect DIO has on hepatic CD36 protein expression and the functional consequence of this in terms of hepatic triglyceride storage and secretion. In addition, in vivo adenoviral gene delivery of CD36 to the livers of lean mice was performed to determine if increased hepatic CD36 protein was sufficient to alter hepatic fatty acid uptake and triglyceride storage and secretion. RESULTS: During DIO, CD36 protein levels in the liver are significantly elevated, and these elevated levels correlate with increased hepatic triglyceride storage and secretion. These alterations in liver lipid storage and secretion were also observed upon forced expression of hepatic CD36 in the absence of DIO and were accompanied with a marked rise in hepatic fatty acid uptake in vivo, demonstrating that increased CD36 expression is sufficient to recapitulate the aberrant liver lipid handling observed in DIO. CONCLUSIONS: Increased expression of hepatic CD36 protein in response to DIO is sufficient to exacerbate hepatic triglyceride storage and secretion. As these CD36-mediated effects contribute to the dyslipidemia that often precedes the development of type 2 diabetes, increased hepatic CD36 expression likely plays a causative role in the pathogenesis of type 2 diabetes. PMID- 17728376 TI - Effects of genetic variation in the human retinol binding protein-4 gene (RBP4) on insulin resistance and fat depot-specific mRNA expression. AB - OBJECTIVE: Serum retinol binding protein 4 (RBP4) is a new liver- and adipocyte derived signal that may contribute to insulin resistance. Therefore, the RBP4 gene represents a plausible candidate gene involved in susceptibility to type 2 diabetes. RESEARCH DESIGN AND METHODS: In this study, the RBP4 gene was sequenced in DNA samples from 48 nonrelated Caucasian subjects. Five novel and three known single nucleotide polymorphisms (SNPs) were identified. Furthermore, five recently reported SNPs were genotyped in 90 subjects. Six SNPs, representative of their linkage disequilibrium groups, were then genotyped in 934 diabetic and 716 nondiabetic subjects. RESULTS: A haplotype of six common SNPs (A-G-G-T-G-C) was significantly increased in 934 case subjects with type 2 diabetes compared with 537 healthy control subjects with normal glucose tolerance (P = 0.02; odds ratio 1.37 [95% CI 1.05-1.79]). Furthermore, in the cohort of 716 nondiabetic Caucasian subjects, carriers of the A-G-G-T-G-C haplotype had significantly higher mean fasting plasma insulin and 2-h plasma glucose than subjects without the haplotype. Two single SNPs (rs10882283 and rs10882273) were also associated with BMI, waist-to-hip ratio, and fasting plasma insulin, and several SNPs were associated with circulating free fatty acids (all adjusted P < 0.05). In addition, subjects carrying a previously reported diabetes-associated haplotype had significantly higher mRNA levels in visceral adipose tissue (adjusted P < 0.05) in a subgroup of nondiabetic subjects (n = 170) with measurements of RBP4 mRNA expression in visceral and subcutaneous fat depots. CONCLUSIONS: Our data indicate a role of RBP4 genetic variation in susceptibility to type 2 diabetes and insulin resistance, possibly through an effect on RBP4 expression. PMID- 17728377 TI - Synchronization among mechanisms of renal autoregulation is reduced in hypertensive rats. AB - We searched for synchronization among autoregulation mechanisms using wavelet transforms applied to tubular pressure recordings in nephron pairs from the surface of rat kidneys. Nephrons have two oscillatory modes in the regulation of their pressures and flows: a faster (100-200 mHz) myogenic mode, and a slower (20 40 mHz) oscillation in tubuloglomerular feedback (TGF). These mechanisms interact; the TGF mode modulates both the amplitude and the frequency of the myogenic mode. Nephrons also communicate with each other using vascular signals triggered by membrane events in arteriolar smooth muscle cells. In addition, the TGF oscillation changes in hypertension to an irregular fluctuation with characteristics of deterministic chaos. The analysis shows that, within single nephrons of normotensive rats, the myogenic mode and TGF are synchronized at discrete frequency ratios, with 5:1 most common. There is no distinct synchronization ratio in spontaneously hypertensive rats (SHR). In normotensive rats, full synchronization of both TGF and myogenic modes is the most probable state for pairs of nephrons originating in a common cortical radial artery. For SHR, full synchronization is less probable; most common in SHR is a state of partial synchronization with entrainment between neighboring nephrons for only one of the modes. Modulation of the myogenic mode by the TGF mode is much stronger in hypertensive than in normotensive rats. Synchronization among nephrons forms the basis for an integrated reaction to blood pressure fluctuations. Reduced synchronization in SHR suggests that the effectiveness of the coordinated response is impaired in hypertension. PMID- 17728378 TI - EP2 receptor mediates PGE2-induced cystogenesis of human renal epithelial cells. AB - Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by formation of cysts from tubular epithelial cells. Previous studies indicate that secretion of prostaglandin E2 (PGE2) into cyst fluid and production of cAMP underlie cyst expansion. However, the mechanism by which PGE2 directly stimulates cAMP formation and modulates cystogenesis is still unclear, because the particular E-prostanoid (EP) receptor mediating the PGE2 effect has not been characterized. Our goal is to define the PGE2 receptor subtype involved in ADPKD. We used a three-dimensional cell-culture system of human epithelial cells from normal and ADPKD kidneys in primary cultures to demonstrate that PGE2 induces cyst formation. Biochemical evidence gathered by using real-time RT-PCR mRNA analysis and immunodetection indicate the presence of EP2 receptor in cystic epithelial cells in ADPKD kidney. Pharmacological evidence obtained by using PGE2 selective analogs further demonstrates that EP2 mediates cAMP formation and cystogenesis. Functional evidence for a role of EP2 receptor in mediating cAMP signaling was also provided by inhibiting EP2 receptor expression with transfection of small interfering RNA in cystic epithelial cells. Our results indicate that PGE2 produced in cyst fluid binds to adjacent EP2 receptors located on the apical side of cysts and stimulates EP2 receptor expression. PGE2 binding to EP2 receptor leads to cAMP signaling and cystogenesis by a mechanism that involves protection of cystic epithelial cells from apoptosis. The role of EP2 receptor in mediating the PGE2 effect on stimulating cyst formation may have direct pharmacological implications for the treatment of polycystic kidney disease. PMID- 17728379 TI - Dynamic blood pressure load and nephropathy in the ZSF1 (fa/fa cp) model of type 2 diabetes. AB - Diabetes and increased blood pressure (BP) are believed to interact synergistically in the pathogenesis and progression of diabetic nephropathy. The present studies were performed to examine if there were differences in BP load and/or protective renal autoregulatory capacity between the obese diabetic Zucker fatty /spontaneously hypertensive heart failure F1 hybrid (ZSF1) (fa/fa cp) rats and their lean controls. By approximately 26 wk of age, ZSF1 (n = 13) but not their lean controls (n = 16) had developed substantial proteinuria (180 +/- 19 vs. 16 +/- 1.4 mg/24 h) and glomerulosclerosis (19 +/- 2.4 vs. 0.6 +/- 0.2%; P < 0.001). However, average ambient systolic BP by radiotelemetry (12-26 wk of age) was modestly lower in ZSF1 than in lean controls (130 +/- 1.4 vs. 137 +/- 1.7 mmHg, P < 0.002), although the 24-h BP power spectra showed a mild increase at frequencies <0.1 Hz in the ZSF1. Autoregulatory capacity under anesthesia in response to step changes in perfusion pressure between 100 and 140 mmHg was similarly well preserved in both ZSF1 and lean controls at 16-18 wk of age [autoregulatory indexes (AI) <0.1]. Similarly, differences were not observed for dynamic autoregulation in conscious rats [transfer functions between BP (input) and renal blood flow (output) using chronic Transonic flow probes]. Collectively, these data indicate that the pathogenesis of nephropathy in the ZSF1 model of type 2 diabetic nephropathy is largely independent of differences in systemic BP and/or its potential renal transmission. However, these data do not exclude the possibility that the diabetic milieu may alter the glomerular capillaries in the ZSF1, such that there is an enhanced local susceptibility to injury with even normal glomerular pressures. PMID- 17728380 TI - A novel mechanism of renal blood flow autoregulation and the autoregulatory role of A1 adenosine receptors in mice. AB - Autoregulation of renal blood flow (RBF) is mediated by a fast myogenic response (MR; approximately 5 s), a slower tubuloglomerular feedback (TGF; approximately 25 s), and potentially additional mechanisms. A1 adenosine receptors (A1AR) mediate TGF in superficial nephrons and contribute to overall autoregulation, but the impact on the other autoregulatory mechanisms is unknown. We studied dynamic autoregulatory responses of RBF to rapid step increases of renal artery pressure in mice. MR was estimated from autoregulation within the first 5 s, TGF from that at 5-25 s, and a third mechanism from 25-100 s. Genetic deficiency of A1AR (A1AR /-) reduced autoregulation at 5-25 s by 50%, indicating a residual fourth mechanism resembling TGF kinetics but independent of A1AR. MR and third mechanism were unaltered in A1AR-/-. Autoregulation in A1AR-/- was faster at 5-25 than at 25-100 s suggesting two separate mechanisms. Furosemide in wild-type mice (WT) eliminated the third mechanism and enhanced MR, indicating TGF-MR interaction. In A1AR-/-, furosemide did not further impair autoregulation at 5-25 s, but eliminated the third mechanism and enhanced MR. The resulting time course was the same as during furosemide in WT, indicating that A1AR do not affect autoregulation during furosemide inhibition of TGF. We conclude that at least one novel mechanism complements MR and TGF in RBF autoregulation, that is slower than MR and TGF and sensitive to furosemide, but not mediated by A1AR. A fourth mechanism with kinetics similar to TGF but independent of A1AR and furosemide might also contribute. A1AR mediate classical TGF but not TGF-MR interaction. PMID- 17728381 TI - Time course of neuroanatomical and functional recovery after bilateral pudendal nerve injury in female rats. AB - The pudendal nerve innervates the external urethral sphincter (EUS) and is among the tissues injured during childbirth, which may lead to symptoms of stress urinary incontinence (SUI). To understand the mechanisms of injury and repair, urethral leak-point pressure (LPP) was measured 4 days, 2 wk, or 6 wk after bilateral pudendal nerve crush. Morphometric changes in the distal nerve and EUS were examined by light and electron microscopy. To determine whether recovery resulted from pudendal neuroregeneration, LPP was measured before and after pudendal nerve transection 2 wk after nerve crush. LPP was significantly decreased 4 days after pudendal nerve crush compared with sham-injured animals as well as 2 or 6 wk after nerve crush. LPP was not significantly different 2 or 6 wk after nerve crush compared with sham-injured animals, suggesting that urethral function had returned to normal. Four days after pudendal nerve crush, the EUS branch of the pudendal nerve distal to the injury site showed evidence of nerve degeneration and the EUS appeared disrupted. Two weeks after nerve crush, the distal nerve and EUS both showed evidence of both nerve degeneration and recovery. Two weeks after nerve crush, LPP was significantly decreased after nerve transection. Six weeks after nerve injury, evidence of neuroregeneration was observed in the pudendal nerve and the EUS. This study has demonstrated that functional recovery and neuroregeneration are significant 2 wk after nerve crush, although by anatomical assessment, recovery appears incomplete, suggesting that 2 wk represents an early time point of initial neuroregeneration. PMID- 17728382 TI - Versatile applications of transcriptional pulsing to study mRNA turnover in mammalian cells. AB - Development of transcriptional pulsing approaches using the c-fos and Tet-off promoter systems greatly facilitated studies of mRNA turnover in mammalian cells. However, optimal protocols for these approaches vary for different cell types and/or physiological conditions, limiting their widespread application. In this study, we have further optimized transcriptional pulsing systems for different cell lines and developed new protocols to facilitate investigation of various aspects of mRNA turnover. We apply the Tet-off transcriptional pulsing strategy to investigate ARE-mediated mRNA decay in human erythroleukemic K562 cells arrested at various phases of the cell cycle by pharmacological inhibitors. This application facilitates studies of the role of mRNA stability in control of cell cycle dependent gene expression. To advance the investigation of factors involved in mRNA turnover and its regulation, we have also incorporated recently developed transfection and siRNA reagents into the transcriptional pulsing approach. Using these protocols, siRNA and DNA plasmids can be effectively cotransfected into mouse NIH3T3 cells to obtain high knockdown efficiency. Moreover, we have established a tTA-harboring stable line using human bronchial epithelial BEAS-2B cells and applied the transcriptional pulsing approach to monitor mRNA deadenylation and decay kinetics in this cell system. This broadens the application of the transcriptional pulsing system to investigate the regulation of mRNA turnover related to allergic inflammation. Critical factors that need to be considered when employing these approaches are characterized and discussed. PMID- 17728383 TI - Corticofugal modulation of the tactile response coherence of projecting neurons in the gracilis nucleus. AB - Precise and reproducible spike timing is one of the alternatives of the sensory stimulus encoding. We test coherence (repeatability) of the response patterns elicited in projecting gracile neurons by tactile stimulation and its modulation provoked by electrical stimulation of the corticofugal feedback from the somatosensory (SI) cortex. To gain the temporal structure we adopt the wavelet based approach for quantification of the functional stimulus-neural response coupling. We show that the spontaneous firing patterns (when they exist) are essentially random. Tactile stimulation of the neuron receptive field strongly increases the spectral power in the stimulus and 5- to 15-Hz frequency bands. However, the functional coupling (coherence) between the sensory stimulus and the neural response exhibits ultraslow oscillation (0.07 Hz). During this oscillation the stimulus coherence can temporarily fall below the statistically significant level, i.e., the functional stimulus-response coupling may be temporarily lost for a single neuron. We further demonstrate that electrical stimulation of the SI cortex increases the stimulus coherence for about 60% of cells. We find no significant correlation between the increment of the firing rate and the stimulus coherence, but we show that there is a positive correlation with the amplitude of the peristimulus time histogram. The latter argues that the observed facilitation of the neural response by the corticofugal pathway, at least in part, may be mediated through an appropriate ordering of the stimulus-evoked firing pattern, and the coherence enhancement is more relevant in gracilis nucleus than an increase of the number of spikes elicited by the tactile stimulus. PMID- 17728384 TI - Commissural mirror-symmetric excitation and reciprocal inhibition between the two superior colliculi and their roles in vertical and horizontal eye movements. AB - The functional roles of commissural excitation and inhibition between the two superior colliculi (SCs) are not yet well understood. We previously showed the existence of strong excitatory commissural connections between the rostral SCs, although commissural connections had been considered to be mainly inhibitory. In this study, by recording intracellular potentials, we examined the topographical distribution of commissural monosynaptic excitation and inhibition from the contralateral medial and lateral SC to tectoreticular neurons (TRNs) in the medial or lateral SC of anesthetized cats. About 85% of TRNs examined projected to both the ipsilateral Forel's field H and the contralateral inhibitory burst neuron region where the respective premotor neurons for vertical and horizontal saccades reside. Medial TRNs received strong commissural excitation from the medial part of the opposite SC, whereas lateral TRNs received excitation mainly from its lateral part. Injection of wheat germ agglutinin-horseradish peroxidase into the lateral or medial SC retrogradely labeled many larger neurons in the lateral or medial part of the contralateral SC, respectively. These results indicated that excitatory commissural connections exist between the medial and medial parts and between the lateral and lateral parts of the rostral SCs. These may play an important role in reinforcing the conjugacy of upward and downward saccades, respectively. In contrast, medial SC projections to lateral SC TRNs and lateral SC projections to medial TRNs mainly produce strong inhibition. This shows that regions representing upward saccades inhibit contralateral regions representing downward saccades and vice versa. PMID- 17728386 TI - Visual deprivation alters the development of cortical multisensory integration. AB - It has recently been demonstrated that the maturation of normal multisensory circuits in the cortex of the cat takes place over an extended period of postnatal life. Such a finding suggests that the sensory experiences received during this time may play an important role in this developmental process. To test the necessity of sensory experience for normal cortical multisensory development, cats were raised in the absence of visual experience from birth until adulthood, effectively precluding all visual and visual-nonvisual multisensory experiences. As adults, semichronic single-unit recording experiments targeting the anterior ectosylvian sulcus (AES), a well-defined multisensory cortical area in the cat, were initiated and continued at weekly intervals in anesthetized animals. Despite having very little impact on the overall sensory representations in AES, dark-rearing had a substantial impact on the integrative capabilities of multisensory AES neurons. A significant increase was seen in the proportion of multisensory neurons that were modulated by, rather than driven by, a second sensory modality. More important, perhaps, there was a dramatic shift in the percentage of these modulated neurons in which the pairing of weakly effective and spatially and temporally coincident stimuli resulted in response depressions. In normally reared animals such combinations typically give rise to robust response enhancements. These results illustrate the important role sensory experience plays in shaping the development of mature multisensory cortical circuits and suggest that dark-rearing shifts the relative balance of excitation and inhibition in these circuits. PMID- 17728385 TI - Heterogeneous effects of dopamine on highly localized, voltage-induced Ca2+ accumulation in identified motoneurons. AB - Modulation of synaptic transmission is a major mechanism for the functional reconfiguration of neuronal circuits. Neurotransmitter release and, consequently, synaptic strength are regulated by intracellular Ca(2+) levels in presynaptic terminals. In identified neurons of the lobster pyloric network, we studied localized, voltage-induced Ca(2+) accumulation and its modulation in varicosities on distal neuritic arborizations, which have previously been shown to be sites of synaptic contacts. We previously demonstrated that dopamine (DA) weakens synaptic output from the pyloric dilator (PD) neuron and strengthens synaptic output from the lateral pyloric (LP) and pyloric constrictor (PY) neurons. Here we show that DA modifies voltage-activated Ca(2+) accumulation in many varicosities in ways that are consistent with DA's effects on synaptic transmission: DA elevates Ca(2+) accumulation in LP and PY varicosities and reduces Ca(2+) accumulation in PD varicosities. However, in all three neuron types, we also found varicosities that were unaffected by DA. In the PY neurons, we found that DA can simultaneously increase and decrease voltage-evoked Ca(2+) accumulation at different varicosities, even within the same neuron. These results suggest that regulation of Ca(2+) entry is a common mechanism to regulate synaptic strength in the pyloric network. However, voltage-evoked local Ca(2+) accumulation can be differentially modulated to control Ca(2+)-dependent processes in functionally separate varicosities of a single neuron. PMID- 17728387 TI - A central pattern generator producing alternative outputs: phase relations of leech heart motor neurons with respect to premotor synaptic input. AB - The central pattern generator (CPG) for heartbeat in leeches consists of seven identified pairs of segmental heart interneurons and one unidentified pair. Four of the identified pairs and the unidentified pair of interneurons make inhibitory synaptic connections with segmental heart motor neurons. The CPG produces a side to-side asymmetric pattern of intersegmental coordination among ipsilateral premotor interneurons corresponding to a similarly asymmetric fictive motor pattern in heart motor neurons, and asymmetric constriction pattern of the two tubular hearts: synchronous and peristaltic. Using extracellular techniques, we recorded, in 61 isolated nerve cords, the activity of motor neurons in conjunction with the phase reference premotor heart interneuron, HN(4), and another premotor interneuron that allowed us to assess the coordination mode. These data were then coupled with a previous description of the temporal pattern of premotor interneuron activity in the two coordination modes to synthesize a global phase diagram for the known elements of the CPG and the entire motor neuron ensemble. These average data reveal the stereotypical side-to-side asymmetric patterns of intersegmental coordination among the motor neurons and show how this pattern meshes with the activity pattern of premotor interneurons. Analysis of animal-to-animal variability in this coordination indicates that the intersegmental phase progression of motor neuron activity in the midbody in the peristaltic coordination mode is the most stereotypical feature of the fictive motor pattern. Bilateral recordings from motor neurons corroborate the main features of the asymmetric motor pattern. PMID- 17728388 TI - NMDA receptor trafficking at recurrent synapses stabilizes the state of the CA3 network. AB - Metaplasticity describes the stabilization of synaptic strength such that strong synapses are likely to remain strong while weak synapses are likely to remain weak. A potential mechanism for metaplasticity is a correlated change in both N methyl-D-aspartate (NMDA) receptor-mediated postsynaptic conductance and synaptic strength. Synchronous activation of CA3-CA3 synapses during spontaneous bursts of population activity caused long-term potentiation (LTP) of recurrent CA3-CA3 glutamatergic synapses under control conditions and depotentiation when NMDA receptors were partially blocked by competitive antagonists. LTP was associated with a significant increase in membrane-bound NMDA receptors, whereas depotentiation was associated with a significant decrease in membrane-bound NMDA receptors. During burst activity, further depotentiation could be induced by sequential reductions in antagonist concentration, consistent with a depotentiation-associated reduction in membrane-bound NMDA receptors. The decrease in number of membrane-bound NMDA receptors associated with depotentiation reduced the probability of subsequent potentiation of weakened synapses in the face of ongoing synchronous network activity. This molecular mechanism stabilizes synaptic strength, which in turn stabilizes the state of the CA3 neuronal network, reflected in the frequency of spontaneous population bursts. PMID- 17728390 TI - Slow brain potential and oscillatory EEG manifestations of impaired temporal preparation in Parkinson's disease. AB - Performance in behavioral tasks is influenced by temporal expectations shaped by the temporal structure of the task. Such implicit temporal preparation is reflected in slow brain potentials and electroencephalographic oscillations and is attributed to interval timing mechanisms that probably depend on intact basal ganglia function. We investigated implicit timing in Parkinson's disease using a choice reaction task with two temporally regular stimulus presentation regimes, both including occasional deviant interstimulus intervals. Control subjects, but not patients, demonstrated temporal preparation in the form of an adjustment in time course of slow brain potentials to the duration of the interstimulus interval. However, in both groups, timing perturbations were accompanied by a slow brain potential amplitude drop at the time of expected stimulus occurrence, demonstrating intact representation of time in patients. In patients, oscillatory activity in beta and alpha bands showed attenuated preparatory desynchronization and reduced postmovement event-related synchronization, reflecting abnormal engagement and disengagement of sensorimotor and parietal areas. The results demonstrate profoundly deficient temporal preparation with preserved encoding of temporal information, a dissociation that may be explained by impaired dopamine dependent motor learning. The results are discussed in the context of recent work on oscillatory activity in the basal ganglia. PMID- 17728391 TI - Decoding a new neural machine interface for control of artificial limbs. AB - An analysis of the motor control information content made available with a neural machine interface (NMI) in four subjects is presented in this study. We have developed a novel NMI-called targeted muscle reinnervation (TMR)-to improve the function of artificial arms for amputees. TMR involves transferring the residual amputated nerves to nonfunctional muscles in amputees. The reinnervated muscles act as biological amplifiers of motor commands in the amputated nerves and the surface electromyogram (EMG) can be used to enhance control of a robotic arm. Although initial clinical success with TMR has been promising, the number of degrees of freedom of the robotic arm that can be controlled has been limited by the number of reinnervated muscle sites. In this study we assess how much control information can be extracted from reinnervated muscles using high-density surface EMG electrode arrays to record surface EMG signals over the reinnervated muscles. We then applied pattern classification techniques to the surface EMG signals. High accuracy was achieved in the classification of 16 intended arm, hand, and finger/thumb movements. Preliminary analyses of the required number of EMG channels and computational demands demonstrate clinical feasibility of these methods. This study indicates that TMR combined with pattern-recognition techniques has the potential to further improve the function of prosthetic limbs. In addition, the results demonstrate that the central motor control system is capable of eliciting complex efferent commands for a missing limb, in the absence of peripheral feedback and without retraining of the pathways involved. PMID- 17728392 TI - Cell-type specific modulation of intrinsic firing properties and subthreshold membrane oscillations by the M(Kv7)-current in neurons of the entorhinal cortex. AB - The M-current (current through Kv7 channels) is a low-threshold noninactivating potassium current that is suppressed by muscarinic agonists. Recent studies have shown its role in spike burst generation and intrinsic subthreshold theta resonance, both of which are important for memory function. However, little is known about its role in principal cells of the entorhinal cortex (EC). In this study, using whole cell patch recording techniques in a rat EC slice preparation, we have examined the effects of the M-current blockers linopirdine and XE991 on the membrane dynamics of principal cells in the EC. When the M-current was blocked, layer II nonstellate cells (non-SCs) and layer III cells switched from tonic discharge to intermittent firing mode, during which layer II non-SCs showed high-frequency short-duration spike bursts due to increased fast spike afterdepolarization (ADP). When three spikes were elicited at 50 Hz, these two types of cells reacted with a slow ADP that drove delayed firing. In contrast, layer II stellate cells (SCs) and layer V cells never displayed intermittent firing, bursting behavior, or delayed firing. Under the M-current block, intrinsic excitability increased significantly in layer III and layer V cells but not in layer II SCs and non-SCs. The M-current block also had contrasting effects on the subthreshold excitability, greatly suppressing the subthreshold membrane potential oscillations in layer V cells but not in layer II SCs. Modulation of the M-current thus shifts the firing behavior, intrinsic excitability, and subthreshold membrane potential oscillations of EC principal cells in a cell-type dependent manner. PMID- 17728393 TI - Leptin requires canonical migratory signaling pathways for induction of monocyte and macrophage chemotaxis. AB - The growing worldwide obesity epidemic is frequently linked to an increased risk of developing diseases such as diabetes, cardiovascular disease, and cancer. These diseases are associated with the infiltration of macrophages in white adipose tissue (WAT), the artery wall, and tumors, respectively; and these macrophages likely contribute to disease progression and pathogenesis. Abdominal WAT, adipose tissue surrounding the heart and artery wall, as well as carcinoma cells, secrete many factors that could induce macrophage infiltration. Leptin is an adipocyte-secreted hormone, and deficiency of either leptin or its receptor has been shown to cause morbid obesity in animals and in humans. However, what is more commonly noted in human obesity is the presence of central leptin resistance leading to hyperleptinemia. As leptin receptors are present on macrophages, we hypothesized that leptin could act as a monocyte/macrophage chemoattractant. Our current study demonstrates: 1) leptin is a potent chemoattractant for monocytes and macrophages, inducing maximal chemotactic responses at 1 ng/ml; 2) leptin mediated chemotaxis requires the presence of full-length leptin receptors on migrating cells; 3) leptin causes increased influx of intracellular calcium in macrophages; and 4) activation of janus kinase/signal transducers and activators of transduction (JAK/STAT), mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K) pathways are all necessary for leptin induced macrophage migration. Taken together, these data demonstrate that leptin is a potent monocyte/macrophage chemoattractant in vitro and that canonical cell motility machinery is activated upon macrophage exposure to leptin. These data have implications for the impact of hyperleptinemia on obesity-related pathophysiological conditions such as diabetes, cardiovascular disease, and cancer. PMID- 17728389 TI - Visual-shift adaptation is composed of separable sensory and task-dependent effects. AB - Visuomotor coordination requires both the accurate alignment of spatial information from different sensory streams and the ability to convert these sensory signals into accurate motor commands. Both of these processes are highly plastic, as illustrated by the rapid adaptation of goal-directed movements following exposure to shifted visual feedback. Although visual-shift adaptation is a widely used model of sensorimotor learning, the multifaceted adaptive response is typically poorly quantified. We present an approach to quantitatively characterizing both sensory and task-dependent components of adaptation. Sensory aftereffects are quantified with "alignment tests" that provide a localized, two dimensional measure of sensory recalibration. These sensory effects obey a precise form of "additivity," in which the shift in sensory alignment between vision and the right hand is equal to the vector sum of the shifts between vision and the left hand and between the right and left hands. This additivity holds at the exposure location and at a second generalization location. These results support a component transformation model of sensory coordination, in which eye hand and hand-hand alignment relies on a sequence of shared sensory transformations. We also ask how these sensory effects compare with the aftereffects measured in target reaching and tracking tasks. We find that the aftereffect depends on both the task performed during feedback-shift exposure and on the testing task. The results suggest the presence of both a general sensory recalibration and task-dependent sensorimotor effect. The task-dependent effect is observed in highly stereotyped reaching movements, but not in the more variable tracking task. PMID- 17728394 TI - Lysoplasmenylcholine increases neutrophil adherence to human coronary artery endothelial cells. AB - We demonstrated previously that thrombin stimulation of human coronary artery endothelial cells (HCAEC) results in release of choline lysophospholipids [lysophosphatidylcholine (lysoPtdCho) and lysoplasmenylcholine (lysoPlsCho)]. These amphiphilic metabolites have been implicated in arrhythmogenesis following the onset of myocardial ischemia, but studies examining their direct effects on the vasculature remain limited. We and others have shown that thrombin and lysoPtdCho can increase cell surface adhesion molecules and adherence of circulating inflammatory cells to the endothelium. This study supports our hypothesis that these changes may be mediated, at least in part, by lysoPlsCho, thus implicating this metabolite as an inflammatory mediator in the coronary vasculature and a modulator of the progression of atherosclerosis. Apical stimulation of HCAEC with thrombin resulted in the production and release of choline lysophospholipids from the apical surface of the HCAEC monolayer. Basolateral stimulation had no effect on choline lysophospholipid production or release from either the apical or basolateral surface of the HCAEC monolayer. Incubation of HCAEC with lysoPlsCho or lysoPtdCho resulted in similar increases in HCAEC surface expression of P-selectin and E-selectin. Furthermore, lysoPlsCho increased cell surface expression of P-selectin, E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 with a time course similar to that of thrombin stimulation. Increased presence of cell surface adhesion molecules may contribute to the significant increase in adherence of neutrophils to either thrombin- or lysoPlsCho-stimulated HCAEC. These results demonstrate that the presence of thrombin at sites of vascular injury in the coronary circulation, resulting in increased choline lysophospholipid release from the HCAEC apical surface, has the potential to propagate vascular inflammation by upregulation of adhesion molecules and recruitment of circulating inflammatory cells to the endothelium. PMID- 17728395 TI - Electron microprobe analysis of rabbit ciliary epithelium indicates enhanced secretion posteriorly and enhanced absorption anteriorly. AB - The rate of aqueous humor formation sequentially across the pigmented (PE) and nonpigmented (NPE) ciliary epithelial cell layers may not be uniform over the epithelial surface. Because of the tissue's small size and complex geometry, this possibility cannot be readily tested by conventional techniques. Rabbit iris ciliary bodies were divided, incubated, quick-frozen, cryosectioned, and freeze dried for electron probe X-ray microanalysis of the elemental contents of the PE and NPE cells. We confirmed that preincubation with ouabain to block Na(+),K(+) ATPase increases Na(+) and decreases K(+) contents far more anteriorly than posteriorly. The anterior and posterior regions were the iridial portion of the primary ciliary processes and the pars plicata, respectively. Following interruption of gap junctions with heptanol, ouabain produced smaller changes in anterior PE cells, possibly reflecting higher Na(+) or K(+) permeability of anterior NPE cells. Inhibiting Na(+) entry selectively with amiloride, benzamil, or dimethylamiloride reduced anterior effects of ouabain by approximately 50%. Regional dependence of net secretion was also assessed with hypotonic stress, which stimulates ciliary epithelial cell regulatory volume decrease (RVD) and net Cl(-) secretion. In contrast to ouabain's actions, the RVD was far more marked posteriorly than anteriorly. These results suggest that 1) enhanced Na(+) reabsorption anteriorly, likely through Na(+) channels and Na(+)/H(+) exchange, mediates the regional dependence of ouabain's actions; and 2) secretion may proceed primarily posteriorly, with secondary processing and reabsorption anteriorly. Stimulation of anterior reabsorption might provide a novel strategy for reducing net secretion. PMID- 17728396 TI - Localization of AMP kinase is regulated by stress, cell density, and signaling through the MEK-->ERK1/2 pathway. AB - 5'-AMP-activated protein kinase (AMPK) serves as an energy sensor and is at the center of control for a large number of metabolic reactions, thereby playing a crucial role in Type 2 diabetes and other human diseases. AMPK is present in the nucleus and cytoplasm; however, the mechanisms that regulate the intracellular localization of AMPK are poorly understood. We have now identified several factors that control the distribution of AMPK. Environmental stress regulates the intracellular localization of AMPK, and upon recovery from heat shock or oxidant exposure AMPK accumulates in the nuclei. We show that under normal growth conditions AMPK shuttles between the nucleus and the cytoplasm, a process that depends on the nuclear exporter Crm1. However, nucleocytoplasmic shuttling does not take place in high-density cell cultures, for which AMPK is confined to the cytoplasm. Furthermore, we demonstrate that signaling through the mitogen activated protein kinase kinase (MEK)-->extracellular signal-regulated kinase 1/2 (ERK1/2) cascade plays a crucial role in controlling the proper localization of AMPK. As such, pharmacological inhibitors that interfere with this pathway alter AMPK distribution under nonstress conditions. Taken together, our studies identify novel links between the physiological state of the cell, the activation of MEK-->ERK1/2 signaling, and the nucleocytoplasmic distribution of AMPK. This sets the stage to develop new strategies to regulate the intracellular localization of AMPK and thereby the modification of targets that are relevant to human disease. PMID- 17728397 TI - Association of PI3K-Akt signaling pathway with digitalis-induced hypertrophy of cardiac myocytes. AB - Our previous studies on cardiac myocytes showed that positive inotropic concentrations of the digitalis drug ouabain activated signaling pathways linked to Na(+)-K(+)-ATPase through Src and epidermal growth factor receptor (EGFR) and led to myocyte hypertrophy. In view of the known involvement of phosphatidylinositol 3-kinase (PI3K)-Akt pathways in cardiac hypertrophy, the aim of the present study was to determine whether these pathways are also linked to cardiac Na(+)-K(+)-ATPase and, if so, to assess their role in ouabain-induced myocyte growth. In a dose- and time-dependent manner, ouabain activated Akt and phosphorylation of its substrates mammalian target of rapamycin and glycogen synthase kinase in neonatal rat cardiac myocytes. Akt activation by ouabain was sensitive to PI3K inhibitors and was also noted in adult myocytes and isolated hearts. Ouabain caused a transient increase of phosphatidylinositol 3,4,5 trisphosphate content of neonatal myocytes, activated class IA, but not class IB, PI3K, and increased coimmunoprecipitation of the alpha-subunit of Na(+)-K(+) ATPase with the p85 subunit of class IA PI3K. Ouabain-induced activation of ERK1/2 was prevented by Src, EGFR, and MEK inhibitors, but not by PI3K inhibitors. Activation of Akt by ouabain, however, was sensitive to inhibitors of PI3K and Src, but not to inhibitors of EGFR and MEK. Similarly, ouabain-induced myocyte hypertrophy was prevented by PI3K and Src inhibitors, but not by an EGFR inhibitor. These findings 1) establish the linkage of the class IA PI3K-Akt pathway to Na(+)-K(+)-ATPase and the essential role of this linkage to ouabain induced myocyte hypertrophy and 2) suggest cross talk between these PI3K-Akt pathways and the signaling cascades previously identified to be associated with cardiac Na(+)-K(+)-ATPase. PMID- 17728398 TI - nPKCepsilon, a P2Y2-R downstream effector in regulated mucin secretion from airway goblet cells. AB - Airway goblet cell mucin secretion is controlled by agonist activation of P2Y(2) purinoceptors, acting through Gq/PLC, inositol-1,4,5-trisphosphate (IP(3)), diacylglycerol, Ca(2+) and protein kinase C (PKC). Previously, we showed that SPOC1 cells express cPKCalpha, nPKCdelta, nPKCepsilon, and nPKCeta; of these, only nPKCdelta translocated to the membrane in correlation with mucin secretion (Abdullah LH, Bundy JT, Ehre C, Davis CW. Am J Physiol Lung Physiol 285: L149 L160, 2003). We have verified these results and pursued the identity of the PKC effector isoform by testing the effects of altered PKC expression on regulated mucin release using SPOC1 cell and mouse models. SPOC1 cells overexpressing cPKCalpha, nPKCdelta, and nPKCeta had the same levels of ATPgammaS- and phorbol 1,2-myristate-13-acetate (PMA)-stimulated mucin secretion as the levels in empty retroviral vector expressing cells. Secretagogue-induced mucin secretion was elevated only in cells overexpressing nPKCepsilon (14.6 and 23.5%, for ATPgammaS and PMA). Similarly, only SPOC1 cells infected with a kinase-deficient nPKCepsilon exhibited the expected diminution of stimulated mucin secretion, relative to wild-type (WT) isoform overexpression. ATPgammaS-stimulated mucin secretion from isolated, perfused mouse tracheas was diminished in P2Y(2)-R null mice by 82% relative to WT mice, demonstrating the utility of mouse models in studies of regulated mucin secretion. Littermate WT and nPKCdelta knockout (KO) mice had nearly identical levels of stimulated mucin secretion, whereas mucin release was nearly abolished in nPKCepsilon KO mice relative to its WT littermates. We conclude that nPKCepsilon is the effector isoform downstream of P2Y(2)-R activation in the goblet cell secretory response. The translocation of nPKCdelta observed in activated cells is likely not related to mucin secretion but to some other aspect of goblet cell biology. PMID- 17728399 TI - Profile of Richard P. Novick. PMID- 17728400 TI - Transcriptome-wide analysis of blood vessels laser captured from human skin and chronic wound-edge tissue. AB - Chronic wounds represent a substantial public health problem. The development of tools that would enable sophisticated scrutiny of clinical wound tissue material is highly desirable. This work presents evidence enabling rapid specific identification and laser capture of blood vessels from human tissue in a manner which lends itself to successful high-density (U133A) microarray analysis. Such screening of transcriptome followed by real-time PCR and immunohistochemical verification of candidate genes and their corresponding products were performed by using 3 mm biopsies. Of the 18,400 transcripts and variants screened, a focused set of 53 up-regulated and 24 down-regulated genes were noted in wound derived blood vessels compared with blood vessels from intact human skin. The mean abundance of periostin in wound-site blood vessels was 96-fold higher. Periostin is known to be induced in response to vascular injury and its expression is associated with smooth muscle cell differentiation in vitro and promotes cell migration. Forty-fold higher expression of heparan sulfate 6-O endosulfatase1 (Sulf1) was noted in wound-site vessels. Sulf1 has been recently recognized to be anti-angiogenic. During embryonic vasculogenesis, CD24 expression is down-regulated in human embryonic stem cells. Wound-site vessels had lower CD24 expression. The findings of this work provide a unique opportunity to appreciate the striking contrast in the transcriptome composition in blood vessels collected from the intact skin and from the wound-edge tissue. Sets of genes with known vascular functions but never connected to wound healing were identified to be differentially expressed in wound-derived blood vessels paving the way for innovative clinically relevant hypotheses. PMID- 17728402 TI - A metabolic pathway leading to mannosylfructose biosynthesis in Agrobacterium tumefaciens uncovers a family of mannosyltransferases. AB - A metabolic pathway for biosynthesis of the nonreducing disaccharide mannosylfructose (beta-fructofuranosyl-alpha-mannopyranoside), an important osmolyte in Agrobacterium tumefaciens, was discovered. We have identified and functionally characterized two ORFs that correspond to genes (named mfpsA and mfppA) encoding the rare enzymes mannosylfructose-phosphate synthase and mannosylfructose-phosphate phosphatase, an associated phosphohydrolase. The mfpsA and mfppA genes are arranged in an operon structure, whose transcription is up regulated by NaCl, resulting in the accumulation of mannosylfructose in the cells. Not only is the biosynthesis of mannosylfructose mechanistically similar to that of sucrose, but the corresponding genes for the biosynthesis of both disaccharides are also phylogenetic close relatives. Importantly, a protein phylogeny analysis indicated that mannosylfructose-phosphate synthase defines a unique group of mannosyltransferases. PMID- 17728401 TI - Ancient bacteria show evidence of DNA repair. AB - Recent claims of cultivable ancient bacteria within sealed environments highlight our limited understanding of the mechanisms behind long-term cell survival. It remains unclear how dormancy, a favored explanation for extended cellular persistence, can cope with spontaneous genomic decay over geological timescales. There has been no direct evidence in ancient microbes for the most likely mechanism, active DNA repair, or for the metabolic activity necessary to sustain it. In this paper, we couple PCR and enzymatic treatment of DNA with direct respiration measurements to investigate long-term survival of bacteria sealed in frozen conditions for up to one million years. Our results show evidence of bacterial survival in samples up to half a million years in age, making this the oldest independently authenticated DNA to date obtained from viable cells. Additionally, we find strong evidence that this long-term survival is closely tied to cellular metabolic activity and DNA repair that over time proves to be superior to dormancy as a mechanism in sustaining bacteria viability. PMID- 17728403 TI - Genomics, biogeography, and the diversification of placental mammals. AB - Previous molecular analyses of mammalian evolutionary relationships involving a wide range of placental mammalian taxa have been restricted in size from one to two dozen gene loci and have not decisively resolved the basal branching order within Placentalia. Here, on extracting from thousands of gene loci both their coding nucleotide sequences and translated amino acid sequences, we attempt to resolve key uncertainties about the ancient branching pattern of crown placental mammals. Focusing on approximately 1,700 conserved gene loci, those that have the more slowly evolving coding sequences, and using maximum-likelihood, Bayesian inference, maximum parsimony, and neighbor-joining (NJ) phylogenetic tree reconstruction methods, we find from almost all results that a clade (the southern Atlantogenata) composed of Afrotheria and Xenarthra is the sister group of all other (the northern Boreoeutheria) crown placental mammals, among boreoeutherians Rodentia groups with Lagomorpha, and the resultant Glires is close to Primates. Only the NJ tree for nucleotide sequences separates Rodentia (murids) first and then Lagomorpha (rabbit) from the other placental mammals. However, this nucleotide NJ tree still depicts Atlantogenata and Boreoeutheria but minus Rodentia and Lagomorpha. Moreover, the NJ tree for amino acid sequences does depict the basal separation to be between Atlantogenata and a Boreoeutheria that includes Rodentia and Lagomorpha. Crown placental mammalian diversification appears to be largely the result of ancient plate tectonic events that allowed time for convergent phenotypes to evolve in the descendant clades. PMID- 17728404 TI - Aryl hydrocarbon receptor nuclear translocator-like (BMAL1) is associated with susceptibility to hypertension and type 2 diabetes. AB - Many aspects of physiology and behavior follow a circadian rhythm. Brain and muscle Arnt-like protein-1 (BMAL1) is a key component of the mammalian molecular clock, which controls circadian oscillations. In the rat, the gene encoding Bmal1 is located within hypertension susceptibility loci. We analyzed the SNP distribution pattern in a congenic interval associated with hypertension in the spontaneously hypertensive rat (SHR), and we show that Bmal1 maps close to a region genetically divergent between SHR and its normotensive (Wistar-Kyoto) counterpart. Bmal1 sequencing in rat strains identified 19 polymorphisms, including an SHR promoter variant that significantly affects Gata-4 activation of transcription in transient transfection experiments. A genetic association study designed to test the relevance of these findings in 1,304 individuals from 424 families primarily selected for type 2 diabetes showed that two BMAL1 haplotypes are associated with type 2 diabetes and hypertension. This comparative genetics finding translated from mouse and rat models to human provides evidence of a causative role of Bmal1 variants in pathological components of the metabolic syndrome. PMID- 17728406 TI - Detection of emerging diseases in occupational health: usefulness and limitations of the application of pharmacosurveillance methods to the database of the French National Occupational Disease Surveillance and Prevention network (RNV3P). AB - OBJECTIVE: To test data mining methods used in pharmacosurveillance in order to identify potential emerging disease-nuisance associations in the national occupational disease surveillance and prevention network (RNV3P) database. METHODS: Proportional reporting ratios (PRR) used in pharmacosurveillance were applied to detect disproportional reporting of disease-nuisance associations which are not compensated by the national social security system. RESULTS: The 24 785 reports of the RNV3P were grouped into 1344 different disease-nuisance associations reported more than twice, of which 422 did not give entitlement to compensation by the social security system. Among these associations, 162 were potentially emergent and generated a signal, of which eight associations involve cancer. CONCLUSION: This work is the first stage of an exploratory investigation submitting the questions raised to experts and involving participants in the network in reflection on the hypotheses generated. PMID- 17728405 TI - Proteome-wide identification of family member-specific natural substrate repertoire of caspases. AB - Caspases are proteolytic enzymes that are essential for apoptosis. Understanding the many discrete and interacting signaling pathways mediated by caspases requires the identification of the natural substrate repertoire for each caspase of interest. Using an amplification-based protein selection technique called mRNA display, we developed a high-throughput screen platform for caspase family member specific substrates on a proteome-wide scale. A large number of both known and previously uncharacterized caspase-3 substrates were identified from the human proteome. The proteolytic features of these selected substrates, including their cleavage sites and specificities, were characterized. Substrates that were cleaved only by caspase-8 or granzyme B but not by caspase-3, were readily selected. The method can be widely applied for efficient and systematic identification of the family member specific natural substrate repertoire of any caspase in an organism of interest, in addition to that of numerous other proteases with high specificity. PMID- 17728407 TI - Low medically certified sickness absence among employees with poor health status predicts future health improvement: the Whitehall II study. AB - BACKGROUND: High sickness absence is associated with poor health status, but it is not known whether low levels of sickness absence among people with poor health predict future health improvement. OBJECTIVE: To examine the association between medically certified sickness absence and subsequent change in health among initially unhealthy employees. METHODS: 5210 employees (3762 men, 1448 women) whose self-rated health status remained stable (either good or poor) between data phases 1 and 2 were divided into three groups according to their rate of medically certified absences during this period (0 vs >0-5 vs >5 absence spells longer than 7 days per 10 person-years). Subsequent change in health status was determined by self-rated health at follow-up (phase 3). RESULTS: After adjustment for age and sex, there was a strong contemporaneous association between lower sickness absence and better health status. Among participants reporting poor health, low absence was associated with subsequent improvement in health status (odds ratio 2.66, 95% CI 1.78 to 4.02 for no absence vs >5 certified spells per 10 years). This association was only partially explained by known existing morbidity, socioeconomic position and risk factors. CONCLUSIONS: Low levels of medically certified sickness absence seem to be associated with positive change in health status among employees in poor health. Further research is needed to examine whether lower sickness absence also marks a more favourable prognosis for specific diseases. PMID- 17728408 TI - Approaching the challenge of bipolar depression: results from STEP-BD. PMID- 17728409 TI - A developmental perspective on the controversy surrounding the use of SSRIs to treat pediatric depression. PMID- 17728410 TI - Depression and coronary heart disease: more pieces of the puzzle. PMID- 17728411 TI - Aripiprazole: what is the role of dopamine D(2) receptor partial agonism? PMID- 17728412 TI - Issues for DSM-V: how should obsessive-compulsive and related disorders be classified? PMID- 17728413 TI - Psychiatrists, mental illness, and violence. PMID- 17728414 TI - Huntington's disease: getting closer. PMID- 17728416 TI - Antidepressant use in the postpartum period: practical considerations. PMID- 17728415 TI - Delayed-onset posttraumatic stress disorder: a systematic review of the evidence. AB - OBJECTIVE: Since the diagnosis of delayed-onset posttraumatic stress disorder (PTSD) was introduced in DSM-III, there has been controversy over its prevalence and even its existence. The authors sought to resolve discrepant findings concerning the prevalence of delayed-onset PTSD by conducting a systematic review of the evidence. METHOD: A literature search was conducted for case reports and group studies with adequate measurement of delayed-onset PTSD according to DSM criteria. Studies that met inclusion criteria were examined for the defined length of delay for delayed-onset PTSD, presence of symptoms before full diagnostic criteria were met, length of follow-up, prevalence estimates, and other variables. Studies were also examined for differences between immediate onset PTSD, delayed-onset PTSD, and no-PTSD cases. RESULTS: Ten case studies and 19 group studies met criteria for inclusion in the review. Studies consistently showed that delayed-onset PTSD in the absence of any prior symptoms was rare, whereas delayed onsets that represented exacerbations or reactivations of prior symptoms accounted on average for 38.2% and 15.3%, respectively, of military and civilian cases of PTSD. CONCLUSIONS: The discrepant findings in the literature concerning prevalence can be largely, but not completely, explained as being due to definitional issues. Little is known about what distinguishes the delayed onset and immediate-onset forms of the disorder. Continuing scientific study of delayed-onset PTSD would benefit if future editions of DSM were to adopt a definition that explicitly accepts the likelihood of at least some prior symptoms. PMID- 17728417 TI - Alternative perspectives on psychodynamic psychotherapy of borderline personality disorder: the case of "Ellen". PMID- 17728419 TI - Adjunctive antidepressant use and symptomatic recovery among bipolar depressed patients with concomitant manic symptoms: findings from the STEP-BD. AB - OBJECTIVE: Practice guidelines have advised against treating patients with antidepressants during bipolar mixed states or dysphoric manias. However, few studies have examined the outcomes of patients with co-occurring manic and depressive symptoms who are treated with antidepressants plus mood stabilizing drugs. METHOD: The authors compared outcomes in patients with bipolar disorder who received a mood stabilizing agent with versus without an antidepressant for a bipolar depressive episode accompanied by > or = 2 concurrent manic symptoms. The 335 participants were drawn from the first 2,000 enrollees in the National Institute of Mental Health (NIMH) Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Kaplan-Meier survival curves and Cox regression models were used to compare time to recovery. General linear models examined the relationship between antidepressant use or mania symptom load at the study entry and mania or depression symptom severity at the 3-month follow-up. RESULTS: Adjunctive antidepressant use was associated with significantly higher mania symptom severity at the 3-month follow-up. The probability of recovery at 3 months was lower among patients with higher baseline depression severity. Antidepressant use neither hastened nor prolonged time to recovery once potential confounding factors were covaried in a Cox regression model. CONCLUSIONS: In bipolar depression accompanied by manic symptoms, antidepressants do not hasten time to recovery relative to treatment with mood stabilizers alone, and treatment with antidepressants may lead to greater manic symptom severity. These findings are consistent with those from the STEP-BD randomized trial for pure bipolar depression, in which adjunctive antidepressants did not yield higher recovery rates than did mood stabilizer monotherapy. PMID- 17728418 TI - Intensive psychosocial intervention enhances functioning in patients with bipolar depression: results from a 9-month randomized controlled trial. AB - OBJECTIVE: Psychosocial interventions are effective adjuncts to pharmacotherapy in delaying recurrences of bipolar disorder; however, to date their effects on life functioning have been given little attention. In a randomized trial, the authors examined the impact of intensive psychosocial treatment plus pharmacotherapy on the functional outcomes of patients with bipolar disorder over the 9 months following a depressive episode. METHOD: Participants were 152 depressed outpatients with bipolar I or bipolar II disorder in the multisite Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study. All patients received pharmacotherapy. Eighty-four patients were randomly assigned to intensive psychosocial intervention (30 sessions over 9 months of interpersonal and social rhythm therapy, cognitive behavior therapy [CBT], or family-focused therapy), and 68 patients were randomly assigned to collaborative care (a 3-session psychoeducational treatment). Independent evaluators rated the four subscales of the Longitudinal Interval Follow-Up Evaluation-Range of Impaired Functioning Tool (LIFE-RIFT) (relationships, satisfaction with activities, work/role functioning, and recreational activities) through structured interviews given at baseline and every 3 months over a 9-month period. RESULTS: Patients in intensive psychotherapy had better total functioning, relationship functioning, and life satisfaction scores over 9 months than patients in collaborative care, even after pretreatment functioning and concurrent depression scores were covaried. No effects of psychosocial intervention were observed on work/role functioning or recreation scores during this 9-month period. CONCLUSIONS: Intensive psychosocial treatment enhances relationship functioning and life satisfaction among patients with bipolar disorder. Alternate interventions focused on the specific cognitive deficits of individuals with bipolar disorder may be necessary to enhance vocational functioning after a depressive episode. PMID- 17728420 TI - Early evidence on the effects of regulators' suicidality warnings on SSRI prescriptions and suicide in children and adolescents. AB - OBJECTIVE: In 2003 and 2004, U.S. and European regulators issued public health warnings about a possible association between antidepressants and suicidal thinking and behavior. The authors assessed whether these warnings discouraged use of antidepressants in children and adolescents and whether they led to increases in suicide rates as a result of untreated depression. METHOD: The authors examined U.S. and Dutch data on prescription rates for selective serotonin reuptake inhibitors (SSRIs) from 2003 to 2005 in children and adolescents (patients up to age 19), as well as suicide rates for children and adolescents, using available data (through 2004 in the United States and through 2005 in the Netherlands). They used Poisson regression analyses to determine the overall association between antidepressant prescription rates and suicide rates, adjusted for sex and age, during the periods preceding and immediately following the public health warnings. RESULTS: SSRI prescriptions for youths decreased by approximately 22% in both the United States and the Netherlands after the warnings were issued. In the Netherlands, the youth suicide rate increased by 49% between 2003 and 2005 and shows a significant inverse association with SSRI prescriptions. In the United States, youth suicide rates increased by 14% between 2003 and 2004, which is the largest year-to-year change in suicide rates in this population since the Centers for Disease Control and Prevention began systematically collecting suicide data in 1979. CONCLUSIONS: In both the United States and the Netherlands, SSRI prescriptions for children and adolescents decreased after U.S. and European regulatory agencies issued warnings about a possible suicide risk with antidepressant use in pediatric patients, and these decreases were associated with increases in suicide rates in children and adolescents. PMID- 17728421 TI - Familial pathways to early-onset suicidal behavior: familial and individual antecedents of suicidal behavior. AB - OBJECTIVE: The authors sought to identify clinical predictors of new-onset suicidal behavior in children of parents with a history of mood disorder and suicidal behavior. METHOD: In a prospective study of offspring of parents with mood disorders, 365 offspring (average age, 20 years) of 203 parents were followed for up to 6 years. Offspring with incident suicide attempts or emergency referrals for suicidal ideation or behavior ("incident events") were compared with offspring without such events on demographic and clinical characteristics. Multivariate analyses were conducted to examine predictors of incident events and predictors of time to incident event. RESULTS: Offspring of probands who had made suicide attempts, compared with offspring of parents with mood disorders who had not made attempts, had a higher rate of incident suicide attempts (4.1% versus 0.6%, relative risk=6.5) as well as overall suicidal events (8.3% versus 1.9%, relative risk=4.4). Mood disorder and self-reported impulsive aggression in offspring and a history of sexual abuse and self-reported depression in parents predicted earlier time to, and greater hazard of, an incident suicidal event. CONCLUSIONS: In offspring of parents with mood disorders, precursors of early onset suicidal behavior include mood disorder and impulsive aggression as well as parental history of suicide attempt, sexual abuse, and self-reported depression. These results suggest that efforts to prevent the familial transmission of early onset suicidal behavior by targeting these domains could reduce the morbidity of suicidal behavior in high-risk youths. PMID- 17728422 TI - Nonresponse to treatment for depression following myocardial infarction: association with subsequent cardiac events. AB - OBJECTIVE: Depression following myocardial infarction is associated with an increased risk of cardiac events, but attempts to alter cardiovascular prognosis by providing antidepressive treatment have not been successful. This may be because of the limited effects of antidepressive treatment on depression itself. The authors assessed whether nonresponse to treatment of post-myocardial infarction depression is associated with new cardiac events. METHOD: The authors made a subgroup analysis of a multicenter randomized, clinical trial on the effects of antidepressant treatment for post-myocardial infarction depression. Patients were enrolled in double-blind, placebo-controlled treatment with mirtazapine (30 mg/day) and, in the case of insufficient treatment response after 8 weeks, open treatment with citalopram. Patients were classified as responders to antidepressants (at least 50% reduction in Hamilton Depression Rating scale [HAM-D] score or HAM-D score <9 at 24 weeks) (N=43) or as nonresponders (N=27) and compared to untreated control subjects (N=98) on cardiac events (cardiac mortality or cardiac-related hospital admission) after 24 weeks post-random assignment and within 18 months after index infarction. RESULTS: The event rate was 25.6% among nonresponders, 11.2% among untreated control subjects, and 7.4% among responders. In relation to untreated comparison subjects, nonresponders had a hazard ratio of 2.66 for new cardiovascular events, which remained after the authors controlled for potential confounders (hazard ratio=2.92). CONCLUSIONS: This study provides further preliminary evidence that nonresponse to treatment of post-myocardial infarction depression may be associated with cardiac events. Efforts should be dedicated to developing more effective treatments for depressed patients with myocardial infarction. PMID- 17728424 TI - Differences in PTSD prevalence and associated risk factors among World Trade Center disaster rescue and recovery workers. AB - OBJECTIVE: This study compared the prevalence and risk factors of current probable posttraumatic stress disorder (PTSD) across different occupations involved in rescue/recovery work at the World Trade Center site. METHOD: Rescue and recovery workers enrolled in the World Trade Center Health Registry who reported working at the World Trade Center site (N=28,962) were included in the analysis. Interviews conducted 2-3 years after the disaster included assessments of demographic characteristics, within-disaster and work experiences related to the World Trade Center, and current probable PTSD. RESULTS: The overall prevalence of PTSD among rescue/recovery workers was 12.4%, ranging from 6.2% for police to 21.2% for unaffiliated volunteers. After adjustments, the greatest risk of developing PTSD was seen among construction/engineering workers, sanitation workers, and unaffiliated volunteers. Earlier start date and longer duration of time worked at the World Trade Center site were significant risk factors for current probable PTSD for all occupations except police, and the association between duration of time worked and current probable PTSD was strongest for those who started earlier. The prevalence of PTSD was significantly higher among those who performed tasks not common for their occupation. CONCLUSIONS: Workers and volunteers in occupations least likely to have had prior disaster training or experience were at greatest risk of PTSD. Disaster preparedness training and shift rotations to enable shorter duration of service at the site may reduce PTSD among workers and volunteers in future disasters. PMID- 17728423 TI - Association of a serotonin transporter polymorphism (5-HTTLPR) with depression, perceived stress, and norepinephrine in patients with coronary disease: the Heart and Soul Study. AB - OBJECTIVE: The short allele of a functional polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) has been shown to interact with stressful life events to predict depression in otherwise healthy individuals. Whether the short allele increases risk for depression associated with the stress of a chronic illness has not been established. METHOD: In a cross-sectional genetic association study, the authors examined the association of 5-HTTLPR with current depression (measured by the Computerized Diagnostic Interview Schedule), perceived stress (measured by the Perceived Stress Scale), and 24-hour urinary norepinephrine excretion in 557 outpatients with chronic coronary disease. RESULTS: Among individuals carrying an s allele, 25% (97 of 383) had current depression, compared with 17% (29 of 174) of l/l homozygotes. The unadjusted odds ratio was 1.6, with a 95% confidence interval (CI) of 1.0-2.6; the age- and gender-adjusted odds ratio was also 1.6 (95% CI=1.0-2.5). Participants carrying an s allele had a higher mean score for perceived stress than l/l homozygotes (5.4 versus 4.7) and a higher rate of moderate or high perceived stress (adjusted odds ratio=1.6, 95% CI=1.1-2.3). Mean 24-hour norepinephrine excretion was higher in s allele carriers (55.6 versus 50.2 mg/day), who were more likely to have norepinephrine values in the highest quartile (adjusted odds ratio=1.7, 95% CI=1.0-3.0). CONCLUSIONS: Among patients with chronic illness, carriers of the s allele of 5-HTTLPR are more vulnerable to depression, perceived stress, and high norepinephrine secretion. These factors may contribute to worse cardiovascular outcomes in these patients. PMID- 17728425 TI - Effectiveness of a mental health court in reducing criminal recidivism and violence. AB - OBJECTIVE: In response to the large-scale involvement of people with mental disorders in the criminal justice system, many communities have created specialized mental health courts in recent years. However, little research has been done to evaluate the criminal justice outcomes of such courts. This study evaluated whether a mental health court can reduce the risk of recidivism and violence by people with mental disorders who have been arrested. METHOD: A retrospective observational design was used to compare the occurrence of new criminal charges for 170 people who entered a mental health court after arrest and 8,067 other adults with mental disorders who were booked into an urban county jail after arrest during the same interval. A matching strategy based on propensity scores was used to adjust analyses for nonrandom selection into mental health court. RESULTS: Propensity-weighted Cox regression analysis, controlling for other potential confounding variables (demographic characteristics, clinical variables, and criminal history), showed that participation in the mental health court program was associated with longer time without any new criminal charges or new charges for violent crimes. Successful completion of the mental health court program was associated with maintenance of reductions in recidivism and violence after graduates were no longer under supervision of the mental health court. CONCLUSIONS: The results indicate that a mental health court can reduce recidivism and violence by people with mental disorders who are involved in the criminal justice system. PMID- 17728426 TI - Adjunctive treatment with a dopamine partial agonist, aripiprazole, for antipsychotic-induced hyperprolactinemia: a placebo-controlled trial. AB - OBJECTIVE: Hyperprolactinemia and associated side effects often occur with antipsychotics. The authors investigated the effect of adjunctive treatment with aripiprazole on hyperprolactinemia and psychopathology in patients with schizophrenia maintained with haloperidol. METHOD: Fifty-six patients with hyperprolactinemia taking haloperidol were enrolled. Haloperidol dose was fixed; aripiprazole was dosed at 15 mg/day for the first 4 weeks, then 30 mg/day for the following 4 weeks. Serum prolactin, haloperidol, and aripiprazole levels were measured. Symptoms and side effects were assessed with the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms, Clinical Global Impression symptom scale, Simpson-Angus Rating Scale, and Barnes Akathisia Rating Scale at weeks 1, 2, 4, 6, and 8. RESULTS: Prolactin levels of patients receiving aripiprazole significantly decreased over time, demonstrating a significant time effect and a time-by-group interaction. In the aripiprazole group, 88.5% of patients at week 8 had prolactin levels normalize compared to 3.6% of patients receiving placebo. Among 11 female patients with menstrual disturbances randomly assigned to aripiprazole, seven patients regained menstruation during the study, whereas none receiving placebo did. Plasma levels of haloperidol were not significantly altered. No significant time effect and time-by-group interactions on BPRS, Scale for the Assessment of Negative Symptoms, and Simpson-Angus Rating Scale scores were noted. CONCLUSIONS: Adjunctive aripiprazole treatment reversed hyperprolactinemia in both sexes, resulting in reinstatement of menstruation in female patients, with no significant effects on psychopathology and extrapyramidal symptoms. Aripiprazole has higher affinity to dopamine D(2) receptors than haloperidol, which is the likely cause of this observation. PMID- 17728427 TI - Differential effects of aripiprazole on D(2), 5-HT(2), and 5-HT(1A) receptor occupancy in patients with schizophrenia: a triple tracer PET study. AB - OBJECTIVE: Aripiprazole has a unique pharmacological profile that includes partial agonism at D(2) receptors, antagonism at 5-HT(2) receptors, and partial agonism at 5-HT(1A) receptors. The authors conducted a positron emission tomography (PET) study to characterize the simultaneous effects of aripiprazole at the D(2), 5-HT(2), and 5-HT(1A) receptors in patients with schizophrenia or schizoaffective disorder. METHOD: Twelve patients who had previously received antipsychotic treatment were randomly assigned to receive 10 mg, 15 mg, 20 mg, or 30 mg of aripiprazole. After at least 14 days of treatment, participants underwent high-resolution PET scans using [(11)C]raclopride, [(18)F]setoperone, and [(11)C]WAY100635. RESULTS: Very high occupancy was observed at striatal D(2) receptors (average putamen, 87%; caudate, 93%; and ventral striatum, 91%), lower occupancy at 5-HT(2) receptors (54%-60%), and even lower occupancy at 5-HT(1A) receptors (16%). D(2) occupancy levels were significantly correlated with plasma drug concentrations, and even the lowest dose (10 mg) led to 85% D(2) occupancy. Extrapyramidal side effects were seen only in two of the four participants with occupancies exceeding 90%. CONCLUSIONS: Aripiprazole exhibits a unique occupancy profile as compared with other conventional and atypical antipsychotics. The threshold for response appears to be higher than 60%, extrapyramidal side effects appear to be uncommon even at occupancies that exceed the conventional extrapyramidal side effects threshold of 80%, and 5-HT(2) occupancy is lower than D(2) occupancy. Implications for aripiprazole's mechanism of action are discussed. PMID- 17728428 TI - Regional cortical thinning in subjects with violent antisocial personality disorder or schizophrenia. AB - Violent behavior is associated with antisocial personality disorder and to a lesser extent with schizophrenia. Neuroimaging studies have suggested that several biological systems are disturbed in schizophrenia, and structural changes in frontal and temporal lobe regions are reported in both antisocial personality disorder and schizophrenia. The neural substrates that underlie violent behavior specifically and their structural analogs, however, remain poorly understood. Nor is it known whether a common biological basis exists for aggressive, impulsive, and violent behavior across these clinical populations. To explore the correlates of violence with brain structure in antisocial personality disorder and schizophrenia, the authors used magnetic resonance imaging data to investigate for the first time, to the authors' knowledge, regional differences in cortical thickness in violent and nonviolent individuals with schizophrenia and/or antisocial personality disorder and in healthy comparison subjects. Subject groups included right-handed men closely matched for demographic variables (total number of subjects=56). Violence was associated with cortical thinning in the medial inferior frontal and lateral sensory motor cortex, particularly in the right hemisphere, and surrounding association areas (Brodmann's areas 10, 11, 12, and 32). Only violent subjects with antisocial personality disorder exhibited cortical thinning in inferior mesial frontal cortices. The biological underpinnings of violent behavior may therefore vary between these two violent subject groups in which the medial frontal cortex is compromised in antisocial personality disorder exclusively, but laminar abnormalities in sensorimotor cortices may relate to violent behavior in both antisocial personality disorder and schizophrenia. PMID- 17728429 TI - Morphology of the cerebral cortex in preclinical Huntington's disease. AB - OBJECTIVE: Cortical morphology was evaluated in subjects with known gene expansion for Huntington's disease and no manifest disease. METHOD: Magnetic resonance imaging scans were obtained for 24 subjects with preclinical Huntington's disease and were compared to those for 24 matched healthy subjects by means of novel imaging methods to quantify aspects of cortical structure. RESULTS: In relation to the comparison subjects, those with preclinical Huntington's disease showed altered cortex morphology with enlargement of gyral crowns and abnormally thin sulci. These changes were manifested in global alterations of gyral and sulcal shape. CONCLUSION: These findings lend support to the notion that, in addition to the degenerative process, abnormal neural development may also be an important process in the pathoetiology of Huntington's disease. PMID- 17728430 TI - Compulsive hoarding and OCD: two distinct disorders? PMID- 17728431 TI - Aripiprazole-induced tardive dyskinesia: the role of tamoxifen. PMID- 17728432 TI - Paradoxical motor syndrome following a switch from atypical neuroleptics to aripiprazole. PMID- 17728433 TI - Restarting clozapine treatment during ablation chemotherapy and stem cell transplant for Hodgkin's lymphoma. PMID- 17728434 TI - Understanding schizophrenia. PMID- 17728435 TI - Initiation of methamphetamine abuse during interferon treatment. PMID- 17728436 TI - Brugada syndrome in a patient treated with lithium. PMID- 17728437 TI - Isolated adrenocorticotropic hormone deficiency presenting with delirium. PMID- 17728438 TI - NeuroMorpho.Org: a central resource for neuronal morphologies. PMID- 17728439 TI - Effects of selective attention on the electrophysiological representation of concurrent sounds in the human auditory cortex. AB - In noisy environments, we use auditory selective attention to actively ignore distracting sounds and select relevant information, as during a cocktail party to follow one particular conversation. The present electrophysiological study aims at deciphering the spatiotemporal organization of the effect of selective attention on the representation of concurrent sounds in the human auditory cortex. Sound onset asynchrony was manipulated to induce the segregation of two concurrent auditory streams. Each stream consisted of amplitude modulated tones at different carrier and modulation frequencies. Electrophysiological recordings were performed in epileptic patients with pharmacologically resistant partial epilepsy, implanted with depth electrodes in the temporal cortex. Patients were presented with the stimuli while they either performed an auditory distracting task or actively selected one of the two concurrent streams. Selective attention was found to affect steady-state responses in the primary auditory cortex, and transient and sustained evoked responses in secondary auditory areas. The results provide new insights on the neural mechanisms of auditory selective attention: stream selection during sound rivalry would be facilitated not only by enhancing the neural representation of relevant sounds, but also by reducing the representation of irrelevant information in the auditory cortex. Finally, they suggest a specialization of the left hemisphere in the attentional selection of fine-grained acoustic information. PMID- 17728441 TI - Attention to painful stimulation enhances gamma-band activity and synchronization in human sensorimotor cortex. AB - A number of cortical regions are involved in processing pain-related information. The SI and SII somatosensory cortices process mainly sensory discriminative attributes but also play an important role in recognition and memory of painful events. Regions such as SII and the posterior insula appear to be the first stations that house processes by which attention profoundly shapes both behavioral responses and subjective pain experience. We investigated the influence of directed attention on pain-induced oscillations and synchronization processes using magnetoencephalogram in combination with an oddball paradigm in 20 healthy subjects. The subject's task was to count rare painful electrical stimuli applied to one finger, while ignoring frequent stimuli at a different finger. A high detection ratio was observed for all blocks and subjects. Early evoked oscillations in the delta-band increased with higher stimulus intensity and directed attention, most prominently at contralateral sensorimotor sites. Furthermore, suppression and rebound of beta activity were observed after painful stimulation. Moreover, induced oscillatory activity in the high gamma-band increased with directed attention, an effect being significantly stronger for high compared with low stimulus intensity. Coupling analysis performed for this high gamma response revealed stronger functional interactions between ipsilateral and contralateral sites during attention. We conclude that pain-induced high frequency activity in sensorimotor areas may reflect an attentional augmentation of processing, leading to enhanced saliency of pain-related signals and thus to more efficient processing of this information by downstream cortical centers. PMID- 17728440 TI - Amyloid beta protein modulates glutamate-mediated neurotransmission in the rat basal forebrain: involvement of presynaptic neuronal nicotinic acetylcholine and metabotropic glutamate receptors. AB - Amyloid beta (Abeta) protein, a 39-43 amino acid peptide deposited in brains of individuals with Alzheimer's disease (AD), has been shown to interact directly with a number of receptor targets including neuronal nicotinic acetylcholine receptors (nAChRs) and glutamate receptors. In this study, we investigated the synaptic effects of Abeta(1-42) on glutamate-mediated neurotransmission in the diagonal band of Broca (DBB), a cholinergic basal forebrain nucleus. Glutamatergic miniature EPSCs (mEPSCs) were recorded using whole-cell patch-clamp recordings from identified cholinergic DBB neurons in rat forebrain slices. In 54% of DBB neurons, bath application of Abeta(1-42) (100 nM), but not Abeta(42-1) (inverse fragment), significantly increased the frequency of mEPSCs without affecting amplitude or kinetic parameters (rise or decay time). In 32% of DBB neurons, bath application of Abeta(1-42) significantly decreased only the frequency but not amplitude of mEPSCs. Application of dihydro-beta-erythroidine (DHbetaE) (an antagonist for the alpha4beta2 subtype of nAChRs) but not alpha bungarotoxin (an antagonist for the alpha7 subtype of nAChRs) blocked Abeta(1-42) mediated increases in mEPSC frequency. The Abeta(1-42)-mediated increase in glutamatergic transmission is thus presynaptic and mediated via non-alpha7 AChRs. In contrast, Abeta(1-42)-mediated decreases in mEPSC frequency could not be antagonized by either DHbetaE or alpha-bungarotoxin. However, the Abeta(1-42) evoked depression in mEPSC frequency was antagonized by (RS)-alpha-methyl-4 carboxyphenyglycine, a nonselective group I/II metabotropic glutamate receptor antagonist. These observations provide further insight into the mechanisms whereby Abeta affects synaptic function in the brain and may be relevant in the context of synaptic failure observed in AD. PMID- 17728442 TI - Critical role of calpain I in mitochondrial release of apoptosis-inducing factor in ischemic neuronal injury. AB - Loss of mitochondrial membrane integrity and release of apoptogenic factors are a key step in the signaling cascade leading to neuronal cell death in various neurological disorders, including ischemic injury. Emerging evidence has suggested that the intramitochondrial protein apoptosis-inducing factor (AIF) translocates to the nucleus and promotes caspase-independent cell death induced by glutamate toxicity, oxidative stress, hypoxia, or ischemia. However, the mechanism by which AIF is released from mitochondria after neuronal injury is not fully understood. In this study, we identified calpain I as a direct activator of AIF release in neuronal cultures challenged with oxygen-glucose deprivation and in the rat model of transient global ischemia. Normally residing in both neuronal cytosol and mitochondrial intermembrane space, calpain I was found to be activated in neurons after ischemia and to cleave intramitochondrial AIF near its N terminus. The truncation of AIF by calpain activity appeared to be essential for its translocation from mitochondria to the nucleus, because neuronal transfection of the mutant AIF resistant to calpain cleavage was not released after oxygen-glucose deprivation. Adeno-associated virus-mediated overexpression of calpastatin, a specific calpain-inhibitory protein, or small interfering RNA mediated knockdown of calpain I expression in neurons prevented ischemia-induced AIF translocation. Moreover, overexpression of calpastatin or knockdown of AIF expression conferred neuroprotection against cell death in neuronal cultures and in hippocampal CA1 neurons after transient global ischemia. Together, these results define calpain I-dependent AIF release as a novel signaling pathway that mediates neuronal cell death after cerebral ischemia. PMID- 17728443 TI - Membrane estrogen receptor-alpha interactions with metabotropic glutamate receptor 1a modulate female sexual receptivity in rats. AB - In rats, female sexual behavior is regulated by a well defined limbic hypothalamic circuit that integrates sensory and hormonal information. Estradiol activation of this circuit results in mu-opioid receptor (MOR) internalization in the medial preoptic nucleus, an important step for full expression of sexual receptivity. Estradiol acts through both membrane and intracellular receptors to influence neuronal activity and behavior, yet the mechanism(s) and physiological significance of estradiol-mediated membrane responses in vivo have remained elusive. Recent in vitro evidence found that stimulation of membrane-associated estrogen receptor-alpha (ER alpha) led to activation of metabotropic glutamate receptor 1a (mGluR1a). Furthermore, mGluR1a signaling was responsible for the observed downstream effects of estradiol. Here we present data that show that ER alpha and mGluR1a directly interact to mediate a rapid estradiol-induced activation of MOR in the medial preoptic nucleus, leading to female sexual receptivity. In addition, blockade of mGluR1a in the arcuate nucleus of the hypothalamus resulted in a significant attenuation of estradiol-induced MOR internalization, leading to diminished female sexual behavior. These results link membrane-initiated estradiol actions to neural events modulating behavior, demonstrating the physiological importance of ER alpha-to-mGluR1a signaling. PMID- 17728444 TI - Chronic interleukin-1beta expression in mouse brain leads to leukocyte infiltration and neutrophil-independent blood brain barrier permeability without overt neurodegeneration. AB - The proinflammatory cytokine interleukin-1beta (IL-1beta) plays a significant role in leukocyte recruitment to the CNS. Although acute effects of IL-1beta signaling in the mouse brain have been well described, studies elucidating the downstream effects of sustained upregulation have been lacking. Using the recently described IL-1beta(XAT) transgenic mouse model, we triggered sustained unilateral hippocampal overexpression of IL-1beta. Transgene induction led to blood-brain barrier leakage, induction of MCP-1 (monocyte chemoattractant protein 1) (CCL2), ICAM-1 (intercellular adhesion molecule 1), and dramatic infiltration of CD45-positive leukocytes comprised of neutrophils, T-cells, macrophages, and dendritic cells. Despite prolonged cellular infiltration of the hippocampus, there was no evidence of neuronal degeneration. Surprisingly, neutrophils were observed in the hippocampal parenchyma as late as 1 year after transgene induction. Their presence was coincident with upregulation of the potent neutrophil chemotactic chemokines KC (keratinocyte-derived chemokine) (CXCL1) and MIP-2 (macrophage inflammatory protein 2) (CXCL2). Knock-out of their sole receptor CXCR2 abrogated neutrophil infiltration but failed to reduce leakage of the blood-brain barrier. PMID- 17728445 TI - The representation of complex images in spatial frequency domains of primary visual cortex. AB - The organization of cat primary visual cortex has been well mapped using simple stimuli such as sinusoidal gratings, revealing superimposed maps of orientation and spatial frequency preferences. However, it is not yet understood how complex images are represented across these maps. In this study, we ask whether a linear filter model can explain how cortical spatial frequency domains are activated by complex images. The model assumes that the response to a stimulus at any point on the cortical surface can be predicted by its individual orientation, spatial frequency, and temporal frequency tuning curves. To test this model, we imaged the pattern of activity within cat area 17 in response to stimuli composed of multiple spatial frequencies. Consistent with the predictions of the model, the stimuli activated low and high spatial frequency domains differently: at low stimulus drift speeds, both domains were strongly activated, but activity fell off in high spatial frequency domains as drift speed increased. To determine whether the filter model quantitatively predicted the activity patterns, we measured the spatiotemporal tuning properties of the functional domains in vivo and calculated expected response amplitudes from the model. The model accurately predicted cortical response patterns for two types of complex stimuli drifting at a variety of speeds. These results suggest that the distributed activity of primary visual cortex can be predicted from cortical maps like those of orientation and SF preference generated using simple, sinusoidal stimuli, and that dynamic visual acuity is degraded at or before the level of area 17. PMID- 17728446 TI - Frequency control of motor patterning by negative sensory feedback. AB - The sensory system plays a key role in the generation of behavior by providing the nervous system with information about the environment and feedback about body movements such that motor output can continuously be adapted to changing circumstances. Although the effects of sensory organs on nervous system function have been demonstrated in many systems, the impact of sensory activity has rarely been studied in conditions in which motor output and sensory activity can interact as they do in behaving animals. In such situations, emergent properties may surface and govern the characteristics of the motor system. We studied the dynamics of sensorimotor interaction with a combination of electrophysiological experiments and computational modeling in the locust flight pattern generator, including its sensory components. The locust flight motor output is produced by a central pattern generator that interacts with phasic sensory feedback from the tegula, a proprioceptor that signals downstroke movement of the wing. We modeled the flight control system, and we tested the model predictions by replacing tegula feedback in the animal with artificial feedback through computer controlled electric stimulation of the appropriate sensory nerves. With reference to the cycle frequency in the locust flight rhythm, our results show that motor patterns can be regulated via the variation of sensory feedback loops. In closed loop conditions, tegula feedback strength determines cycle frequency in the model and the biological preparation such that stronger feedback results in lower frequencies. This regulatory mechanism appears to be a general emergent property of negative feedback systems. PMID- 17728448 TI - A microcircuit model of the frontal eye fields. AB - The cortical control of eye movements is highly sophisticated. Not only can eye movements be made to the most salient target in a visual scene, but they can also be controlled by top-down rules as is required for visual search or reading. The cortical area called frontal eye fields (FEF) has been shown to play a key role in the visual to oculomotor transformations in tasks requiring an eye movement pattern that is not completely reactive, but follows a previously learned rule. The layered, local cortical circuit, which provides the anatomical substrate for all cortical computation, has been studied extensively in primary sensory cortex. These studies led to the concept of a "canonical circuit" for neocortex (Douglas et al., 1989; Douglas and Martin, 1991), which proposes that all areas of neocortex share a common basic circuit. However, it has not ever been explored whether in principle the detailed canonical circuit derived from cat area 17 (Binzegger et al., 2004) could implement the quite different functions of prefrontal cortex. Here, we show that the canonical circuit can, with a few modifications, model the primate FEF. The spike-based network of integrate-and fire neurons was tested in tasks that were used in electrophysiological experiments in behaving macaque monkeys. The dynamics of the model matched those of neurons observed in the FEF, and the behavioral results matched those observed in psychophysical experiments. The close relationship between the model and the cortical architecture allows a detailed comparison of the simulation results with physiological data and predicts details of the anatomical circuit of the FEF. PMID- 17728447 TI - TASK-3 two-pore domain potassium channels enable sustained high-frequency firing in cerebellar granule neurons. AB - The ability of neurons, such as cerebellar granule neurons (CGNs), to fire action potentials (APs) at high frequencies during sustained depolarization is usually explained in relation to the functional properties of voltage-gated ion channels. Two-pore domain potassium (K(2P)) channels are considered to simply hyperpolarize the resting membrane potential (RMP) by increasing the potassium permeability of the membrane. However, we find that CGNs lacking the TASK-3 type K(2P) channel exhibit marked accommodation of action potential firing. The accommodation phenotype was not associated with any change in the functional properties of the underlying voltage-gated sodium channels, nor could it be explained by the more depolarized RMP that resulted from TASK-3 channel deletion. A functional rescue, involving the introduction of a nonlinear leak conductance with a dynamic current clamp, was able to restore wild-type firing properties to adult TASK-3 knock-out CGNs. Thus, in addition to the accepted role of TASK-3 channels in limiting neuronal excitability, by increasing the resting potassium conductance TASK-3 channels also increase excitability by supporting high-frequency firing once AP threshold is reached. PMID- 17728449 TI - Evidence for the flexible sensorimotor strategies predicted by optimal feedback control. AB - Everyday movements pursue diverse and often conflicting mixtures of task goals, requiring sensorimotor strategies customized for the task at hand. Such customization is mostly ignored by traditional theories emphasizing movement geometry and servo control. In contrast, the relationship between the task and the strategy most suitable for accomplishing it lies at the core of our optimal feedback control theory of coordination. Here, we show that the predicted sensitivity to task goals affords natural explanations to a number of novel psychophysical findings. Our point of departure is the little-known fact that corrections for target perturbations introduced late in a reaching movement are incomplete. We show that this is not simply attributable to lack of time, in contradiction with alternative models and, somewhat paradoxically, in agreement with our model. Analysis of optimal feedback gains reveals that the effect is partly attributable to a previously unknown trade-off between stability and accuracy. This yields a testable prediction: if stability requirements are decreased, then accuracy should increase. We confirm the prediction experimentally in three-dimensional obstacle avoidance and interception tasks in which subjects hit a robotic target with programmable impedance. In additional agreement with the theory, we find that subjects do not rely on rigid control strategies but instead exploit every opportunity for increased performance. The modeling methodology needed to capture this extra flexibility is more general than the linear-quadratic methods we used previously. The results suggest that the remarkable flexibility of motor behavior arises from sensorimotor control laws optimized for composite cost functions. PMID- 17728450 TI - Gamma oscillations coordinate amygdalo-rhinal interactions during learning. AB - The rhinal cortices contribute to memory formation by integrating and transferring neocortical information to the hippocampus. Rhinal contributions to memory are likely influenced by the amygdala because strong reciprocal connections exist between these structures. In light of previous data showing that oscillations regulate neuronal activity during memory formation and recall, we tested the possibility that coherent oscillations serve to coordinate amygdalo rhinal activity during learning. To this end, we performed simultaneous extracellular recordings of basolateral amygdala (BLA), perirhinal, and entorhinal activity. We first tested whether there are correlated fluctuations in the power of BLA and rhinal field activity during the waking state. Correlated power fluctuations were most pronounced in the 35-45 Hz band. Within each structure, firing probability fluctuated rhythmically with the fast oscillations, indicating that they were not volume conducted. To test whether fast oscillations coordinate BLA and rhinal activity during learning, animals were trained on a trace-conditioning task in which a visual conditioned stimulus (CS) predicted a food reward after a delay. The predictive value of the CS was learned gradually over 9 d. As learning progressed, the 35-45 Hz power increased in the BLA and rhinal cortices, particularly during the late part of the CS and delay. Moreover, the firing of BLA and rhinal neurons became rhythmically entrained by BLA oscillations at that time. Thus, our data suggest that neuronal interactions are coordinated by fast oscillations in the BLA-rhinal network. By telescoping the periods of effective neuronal interactions in short recurring time windows, these fast oscillations may facilitate rhinal interactions and synaptic plasticity. PMID- 17728451 TI - Differential abilities of SNAP-25 homologs to support neuronal function. AB - The SNAP receptor (SNARE) complex, consisting of synaptosome-associated protein of 25 kDa (SNAP-25), synaptobrevin-2, and syntaxin-1, is involved in synaptic vesicles exocytosis. In addition, SNAP-25 has been implicated in constitutive exocytosis processes required for neurite outgrowth. However, at least three isoforms of SNAP-25 have been reported from neurons: SNAP-23, which is also present in non-neuronal cells, and the two alternative splice variants SNAP-25a and SNAP-25b. Here, we studied the differential ability of these isoforms to support the functions previously broadly ascribed to "SNAP-25." We studied the rescue of snap-25 null neurons in culture with different SNAP-25 homologs. We find that deletion of SNAP-25 leads to strongly reduced neuron survival, and, in the few surviving cells, impaired arborization, reduced spontaneous release, and complete arrest of evoked release. Lentiviral expression of SNAP-25a, SNAP-25b, or SNAP-23 rescued neuronal survival, arborization, amplitude, and frequency of spontaneous events. Also evoked release was rescued by all isoforms, but synchronous release required SNAP-25a/b in both glutamatergic and GABAergic neurons. SNAP-23 supported asynchronous release only, reminiscent of synaptotagmin-1 null neurons. SNAP-25b was superior to SNAP-25a in vesicle priming, resembling the shift to larger releasable vesicle pools that accompanies synaptic maturation. These data demonstrate a differential ability of SNAP-25b, SNAP-25a, and SNAP-23 to support neuronal function. PMID- 17728452 TI - Dendritic backpropagation and the state of the awake neocortex. AB - The spread of somatic spikes into dendritic trees has become central to models of dendritic integrative properties and synaptic plasticity. However, backpropagating action potentials (BPAPs) have been studied mainly in slices, in which they are highly sensitive to multiple factors such as firing frequency and membrane conductance, raising doubts about their effectiveness in the awake behaving brain. Here, we examine the spatiotemporal characteristics of BPAPs in layer 5 pyramidal neurons in the visual cortex of adult, awake rabbits, in which EEG-defined brain states ranged from alert vigilance to drowsy/inattention, and, in some cases, to light sleep. To achieve this, we recorded extracellular spikes from layer 5 pyramidal neurons and field potentials above and below these neurons using a 16-channel linear probe, and applied methods of spike-triggered current source-density analysis to these records (Buzsaki and Kandel, 1998; Swadlow et al., 2002). Precise retinotopic alignment of superficial and deep cortical sites was used to optimize alignment of the recording probe with the axis of the apical dendrite. During the above network states, we studied BPAPs generated spontaneously, antidromically (from corticotectal neurons), or via intense synaptic drive caused by natural visual stimulation. Surprisingly, the invasion of BPAPs as far as 800 microm from the soma was little affected by the network state and only mildly attenuated by high firing frequencies. These data reveal that the BPAP is a robust and highly reliable property of neocortical apical dendrites. These events, therefore, are well suited to provide crucial signals for the control of synaptic plasticity during information-processing brain states. PMID- 17728453 TI - Seizure-associated, aberrant neurogenesis in adult rats characterized with retrovirus-mediated cell labeling. AB - Seizure activity within the hippocampal circuitry not only affects pre-existing structures, but also dramatically increases the number of newborn granule cells. A retroviral strategy was used to label dividing cells and their progeny in the adult dentate gyrus and to analyze the impact of epileptic activity on adult generated cells labeled before or after seizures. We show that epileptic activity led to dramatic changes in the neuronal polarity, migration, and integration pattern of newborn granule cells, depending on the time of birth in relation to the epileptic insult. Aberrant neurons were stably integrated into the dentate circuitry, and the consequences on hippocampal neurogenesis were long lasting. The data presented characterized the consequences of seizure-associated plasticity on adult neurogenesis leading to long-term structural changes in the hippocampal circuitry that might represent a pivotal component of the epileptic disease process. PMID- 17728454 TI - Differential recruitment of the hippocampus, medial prefrontal cortex, and the human motion complex during path integration in humans. AB - Path integration, the ability to sense self-motion for keeping track of changes in orientation and position, constitutes a fundamental mechanism of spatial navigation and a keystone for the development of cognitive maps. Whereas animal path integration is predominantly supported by the head-direction, grid, and place cell systems, the neural foundations are not well understood in humans. Here we used functional magnetic resonance imaging and a virtual rendition of a triangle completion paradigm to test whether human path integration recruits a cortical system similar to that of rodents and nonhuman primates. Participants traveled along two legs of a triangle before pointing toward the starting location. In accordance with animal models, stronger right hippocampal activation predicted more accurate updating of the starting location on a trial-by-trial basis. Moreover, between-subjects fluctuations in response consistency were negatively correlated with bilateral hippocampal and medial prefrontal activation, and bilateral recruitment of the human motion complex (hMT+) covaried with individual path integration capability. Given that these effects were absent in a perceptual control task, the present study provides the first evidence that visual path integration is related to the dynamic interplay of self-motion processing in hMT+, higher-level spatial processes in the hippocampus, and spatial working memory in medial prefrontal cortex. PMID- 17728455 TI - Conductive hearing loss disrupts synaptic and spike adaptation in developing auditory cortex. AB - Although sensorineural hearing loss (SNHL) is known to compromise central auditory structure and function, the impact of milder forms of hearing loss on cellular neurophysiology remains mostly undefined. We induced conductive hearing loss (CHL) in developing gerbils, reared the animals for 8-13 d, and subsequently assessed the temporal features of auditory cortex layer 2/3 pyramidal neurons in a thalamocortical brain slice preparation with whole-cell recordings. Repetitive stimulation of the ventral medial geniculate nucleus (MGv) evoked robust short term depression of the postsynaptic potentials in control neurons, and this depression increased monotonically at higher stimulation frequencies. In contrast, CHL neurons displayed a faster rate of synaptic depression and a smaller asymptotic amplitude. Moreover, the latency of MGv evoked potentials was consistently longer in CHL neurons for all stimulus rates. A separate assessment of spike frequency adaptation in response to trains of injected current pulses revealed that CHL neurons displayed less adaptation compared with controls, although there was an increase in temporal jitter. For each of these properties, nearly identical findings were observed for SNHL neurons. Together, these data show that CHL significantly alters the temporal properties of auditory cortex synapses and spikes, and this may contribute to processing deficits that attend mild to moderate hearing loss. PMID- 17728456 TI - Experience-dependent modification of primary sensory synapses in the mammalian olfactory bulb. AB - Experience-dependent changes in neural circuits have traditionally been investigated several synapses downstream of sensory input. Whether experience can alter the strength of primary sensory synapses remains mostly unknown. To address this issue, we investigated the consequences of odor deprivation on synapses made by olfactory sensory axons in the olfactory bulb of rats. Odor deprivation triggered an increase in the probability of glutamate release from olfactory sensory neuron synapses. Deprivation also increased the amplitude of quantal synaptic currents mediated by AMPA- and NMDA-type glutamate receptors, as well as the abundance of these receptors in the glomerular region. Our results demonstrate that sensory experience is capable of modulating synaptic strength at the earliest stages of information transfer between the environment and an organism. Such compensatory experience-dependent changes may represent a mechanism of sensory gain control. PMID- 17728457 TI - Loss of X-linked mental retardation gene oligophrenin1 in mice impairs spatial memory and leads to ventricular enlargement and dendritic spine immaturity. AB - Loss of oligophrenin1 (OPHN1) function in human causes X-linked mental retardation associated with cerebellar hypoplasia and, in some cases, with lateral ventricle enlargement. In vitro studies showed that ophn1 regulates dendritic spine through the control of Rho GTPases, but its in vivo function remains unknown. We generated a mouse model of ophn1 deficiency and showed that it mimics the ventricles enlargement without affecting the cerebellum morphoanatomy. The ophn1 knock-out mice exhibit behavioral defects in spatial memory together with impairment in social behavior, lateralization, and hyperactivity. Long-term potentiation and mGluR-dependent long-term depression are normal in the CA1 hippocampal area of ophn1 mutant, whereas paired-pulse facilitation is reduced. This altered short-term plasticity that reflects changes in the release of neurotransmitters from the presynaptic processes is associated with normal synaptic density together with a reduction in mature dendritic spines. In culture, inactivation of ophn1 function increases the density and proportion of immature spines. Using a conditional model of loss of ophn1 function, we confirmed this immaturity defect and showed that ophn1 is required at all the stages of the development. These studies show that, depending of the context, ophn1 controls the maturation of dendritic spines either by maintaining the density of mature spines or by limiting the extension of new filopodia. Altogether, these observations indicate that cognitive impairment related to OPHN1 loss of function is associated with both presynaptic and postsynaptic alterations. PMID- 17728458 TI - Repair capacity for platinum-DNA adducts determines the severity of cisplatin induced peripheral neuropathy. AB - The pronounced neurotoxicity of the potent antitumor drug cisplatin frequently results in the onset of peripheral polyneuropathy (PNP), which is assumed to be initially triggered by platination products in the nuclear DNA of affected tissues. To further elucidate the molecular mechanisms, we analyzed in a mouse model the formation and processing of the main cisplatin-induced DNA adduct (guanine-guanine intrastrand cross-link) in distinct neuronal cell types by adduct-specific monoclonal antibodies. Comparison of the adduct kinetics in cisplatin-injected mice either proficient or deficient for nucleotide excision repair (NER) functions revealed the essential role of this DNA repair pathway in protecting differentiated cells of the nervous system from excessive formation of such lesions. Hence, chronic exposure to cisplatin resulted in an accelerated accumulation of unrepaired intrastrand cross-links in neuronal cells of mice with dysfunctional NER. The augmented adduct levels in dorsal root ganglion (DRG) cells of those animals coincided with an earlier onset of PNP-like functional disturbance of their sensory nervous system. Independently from the respective repair phenotype, the amount of persisting DNA cross-links in DRG neurons at a given cumulative dose was significantly correlated to the degree of sensory impairment as measured by electroneurography. Collectively, these findings suggest a new model for the processing of cisplatin adducts in primary neuronal cells and accentuate the crucial role of effectual DNA repair capacity in the target cells for the individual risk of therapy-induced PNP. PMID- 17728460 TI - Rethinking tuning: in vivo whole-cell recordings of the inferior colliculus in awake bats. AB - Tuning curves were recorded with patch electrodes from the inferior colliculus (IC) of awake bats to evaluate the tuning of the inputs to IC neurons, reflected in their synaptic tuning, compared with the tuning of their outputs, expressed in their discharge tuning. A number of unexpected features were revealed with whole cell recordings. Among these was that most neurons responded to tones with inhibition and/or subthreshold excitation over a surprisingly broad frequency range. The synaptic tuning in many cells was at least 1.5-2.0 octaves wide and, on average, was more than twice as wide as the frequency range that evoked discharges even after inhibition was blocked. In most cells, tones evoked complex synaptic response configurations that varied with frequency, suggesting that these cells were not innervated by congruent excitatory and inhibitory projections. Synaptic tuning was not only wide but was also diverse, in which some cells were dominated by excitation (n = 20), others were dominated by excitation with sideband inhibition (n = 21), but most were dominated by inhibition with little evidence of excitation (n = 31). Another unexpected finding was that some cells responded with inhibition to the onset and offset of tones over a wide frequency range, in which the patterns of synaptic responses changed markedly with frequency. These cells never fired to tones at 50 dB sound pressure level but fired to frequency-modulated sweeps at that intensity and were directionally selective. Thus, the features revealed by whole-cell recordings show that the processing in many IC cells results from inputs spectrally broader and more complex than previously believed. PMID- 17728459 TI - Protein kinase Czeta and glycogen synthase kinase-3beta control neuronal polarity in developing rodent enteric neurons, whereas SMAD specific E3 ubiquitin protein ligase 1 promotes neurite growth but does not influence polarity. AB - Enteric nervous system (ENS) precursors migrate extensively before differentiating to form uni-axonal or multi-axonal neurons. ENS precursor survival, neurite growth, and cell migration are all directed by Ret kinase, but downstream signaling pathways are incompletely understood. We now demonstrate that proteins regulating polarity in other cells including partitioning defective 3 (PAR3), PAR6, protein kinase Czeta (PKCzeta), and glycogen synthase kinase 3beta (GSK3beta) are expressed in developing enteric neurons with a polarized distribution. Blocking PKCzeta or GSK3beta reduces ENS precursor migration and induces the formation of multi-axonal neurons. Axon elongation also depends on SMURF1 (SMAD specific E3 ubiquitin protein ligase 1), which promotes RhoA degradation and associates with polarity proteins. SMURF1 inhibition, however, does not increase the number of multi-axonal neurons in ENS precursors. These data link cell surface Ret activation with molecular machinery controlling cytoskeletal dynamics and suggest that polymorphisms influencing PKCzeta or GSK3beta might alter Hirschsprung disease penetrance or expressivity by affecting ENS precursor migration. PMID- 17728461 TI - Increasing sulfatide synthesis in myelin-forming cells of arylsulfatase A deficient mice causes demyelination and neurological symptoms reminiscent of human metachromatic leukodystrophy. AB - Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by the deficiency of arylsulfatase A (ASA). This results in accumulation of sulfated glycosphingolipids, mainly 3-O-sulfogalactosylceramide (sulfatide), in the nervous system and various other organs. In patients, lipid storage causes a progressive loss of myelin leading to various neurological symptoms. The sulfatide storage pattern in ASA-deficient [ASA(-/-)] mice is comparable to humans, but regrettably, the mice do not mimic the myelin pathology. We reasoned that increasing sulfatide storage in this animal model might provoke demyelination. Therefore, we generated transgenic ASA(-/-) [tg/ASA(-/-)] mice overexpressing the sulfatide-synthesizing enzyme galactose-3-O-sulfotransferase-1 in myelinating cells. Indeed, these tg/ASA(-/-) mice displayed a significant increase in sulfatide storage in brain and peripheral nerves. Mice older than 1 year developed severe neurological symptoms. Nerve conduction velocity was significantly reduced in tg/ASA(-/-) mice because of a peripheral neuropathy characterized by hypomyelinated and demyelinated axons. Inhomogeneous myelin thickness in the corpus callosum, increased frequency of hypomyelinated and demyelinated axons in corpus callosum and optic nerve, and substantially reduced myelin basic protein levels are in accordance with loss of myelin in the CNS. Thus, increasing sulfatide storage in ASA(-/-) mice leads to neurological symptoms and morphological alterations that are reminiscent of human MLD. The approach described here may also be applicable to improve other mouse models of lysosomal as well as nonlysosomal disorders. PMID- 17728462 TI - SK channels provide a novel mechanism for the control of frequency tuning in electrosensory neurons. AB - One important characteristic of sensory input is frequency, with sensory neurons often tuned to narrow stimulus frequency ranges. Although vital for many neural computations, the cellular basis of such frequency tuning remains mostly unknown. In the electrosensory system of Apteronotus leptorhynchus, the primary processing of important environmental and communication signals occurs in pyramidal neurons of the electrosensory lateral line lobe. Spike trains transmitted by these cells can encode low-frequency prey stimuli with bursts of spikes and high-frequency communication signals with single spikes. Here, we demonstrate that the selective expression of SK2 channels in a subset of pyramidal neurons reduces their response to low-frequency stimuli by opposing their burst responses. Apamin block of the SK2 current in this subset of cells induced bursting and increased their response to low-frequency inputs. SK channel expression thus provides an intrinsic mechanism that predisposes a neuron to respond to higher frequencies and thus specific, behaviorally relevant stimuli. PMID- 17728463 TI - Neuronal morphogenesis is regulated by the interplay between cyclin-dependent kinase 5 and the ubiquitin ligase mind bomb 1. AB - Neuronal communication requires the coordinated assembly of polarized structures including axons, dendrites, and synapses. Here, we report the identification of a ubiquitin ligase mind bomb 1 (Mib1) in the postsynaptic density and the characterization of its role in neuronal morphogenesis. Expression of Mib1 inhibits neurite outgrowth in cell culture and its gene deletion enhances synaptic growth at the neuromuscular junction in Drosophila. The analysis of Mib1 interactome by mass spectrometry revealed that Mib1 primarily interacts with membrane trafficking proteins [e.g., EEA1 (early endosomal antigen 1), Rab11 interacting proteins, and SNAP25 (synaptosomal-associated protein of 25 kDa)-like protein] and cell adhesion components (e.g., catenin, coronin, dystrobrevin, and syndecan), consistent with its previously reported function in protein sorting. More interestingly, Mib1 is associated with deubiquitinating enzymes, BRCC36 and the mammalian ortholog of fat facets, and a number of kinases, such as casein kinase II, MARK (microtubule affinity regulating kinase)/PAR1, and cyclin dependent kinase 5 (CDK5). Further characterization of the Mib1-CDK5 interaction indicated that the N-terminal domain of Mib1 directly binds to the regulatory subunit p35 of the CDK5 complex. In cell culture, Mib1 induces the relocalization of p35/CDK5 without affecting its degradation. Surprisingly, p35/CDK5 downregulates the protein level of Mib1 by its kinase activity, and completely rescues the Mib1-induced inhibitory effect on neurite morphology. p35/CDK5 also genetically interacts with Mib1 in the fly according to the rough-eye phenotype. The data strongly support that the negative interplay between Mib1 and p35/CDK5 may integrate the activities of multiple pathways during neuronal development. PMID- 17728464 TI - Isoform-selective susceptibility of DISC1/phosphodiesterase-4 complexes to dissociation by elevated intracellular cAMP levels. AB - Disrupted-in-schizophrenia 1 (DISC1) is a genetic susceptibility factor for schizophrenia and related severe psychiatric conditions. DISC1 is a multifunctional scaffold protein that is able to interact with several proteins, including the independently identified schizophrenia risk factor phosphodiesterase-4B (PDE4B). Here we report that the 100 kDa full-length DISC1 isoform (fl-DISC1) can bind members of each of the four gene, cAMP-specific PDE4 family. Elevation of intracellular cAMP levels, so as to activate protein kinase A, caused the release of PDE4D3 and PDE4C2 isoforms from fl-DISC1 while not affecting binding of PDE4B1 and PDE4A5 isoforms. Using a peptide array strategy, we show that PDE4D3 binds fl-DISC1 through two regions found in common with PDE4B isoforms, the interaction of which is supplemented because of the presence of additional PDE4B-specific binding sites. We propose that the additional binding sites found in PDE4B1 underpin its resistance to release during cAMP elevation. We identify, for the first time, a functional distinction between the 100 kDa long DISC1 isoform and the short 71 kDa isoform. Thus, changes in the expression pattern of DISC1 and PDE4 isoforms offers a means to reprogram their interaction and to determine whether the PDE4 sequestered by DISC1 is released after cAMP elevation. The PDE4B-specific binding sites encompass point mutations in mouse Disc1 that confer phenotypes related to schizophrenia and depression and that affect binding to PDE4B. Thus, genetic variation in DISC1 and PDE4 that influence either isoform expression or docking site functioning may directly affect psychopathology. PMID- 17728465 TI - P2X(7) receptor blockade prevents ATP excitotoxicity in oligodendrocytes and ameliorates experimental autoimmune encephalomyelitis. AB - Oligodendrocyte death and demyelination are hallmarks of multiple sclerosis (MS). Here we show that ATP signaling can trigger oligodendrocyte excitotoxicity via activation of calcium-permeable P2X(7) purinergic receptors expressed by these cells. Sustained activation of P2X(7) receptors in vivo causes lesions that are reminiscent of the major features of MS plaques, i.e., demyelination, oligodendrocyte death, and axonal damage. In addition, treatment with P2X(7) antagonists of chronic experimental autoimmune encephalomyelitis (EAE), a model of MS, reduces demyelination and ameliorates the associated neurological symptoms. Together, these results indicate that ATP can kill oligodendrocytes via P2X(7) activation and that this cell death process contributes to EAE. Importantly, P2X(7) expression is elevated in normal-appearing axon tracts in MS patients, suggesting that signaling through this receptor in oligodendrocytes may be enhanced in this disease. Thus, P2X(7) receptor antagonists may be beneficial for the treatment of MS. PMID- 17728466 TI - Single-nucleotide-polymorphism typing and genetic relationships of Salmonella enterica serovar Typhi isolates. AB - Salmonella enterica serovar Typhi is a clone with a low level of variation. We developed a molecular typing method for serovar Typhi using 38 genome-wide single nucleotide polymorphisms (SNPs) as markers detected by PCR-restriction enzyme digestion. The 73 worldwide serovar Typhi isolates studied were separated into 23 SNP profiles and four distinct genetic groups. Serovar Typhi isolates expressing the unique flagellar antigen z66 were found to cluster together and branch off from the ancestral group, suggesting that serovar Typhi was initially monophasic with only an H1 antigen and subsequently gained the z66 antigen. Typing using the 38 SNPs gave a discriminatory power of 0.87, and a minimum of 16 SNPs may be used to achieve the same level of differentiation. The SNP typing method we developed will be a valuable tool for global epidemiology studies of serovar Typhi. PMID- 17728467 TI - Molecular epidemiology of Neisseria meningitidis isolates from an outbreak of meningococcal disease among men who have sex with men, Chicago, Illinois, 2003. AB - We characterized five Neisseria meningitidis serogroup C isolates from a Chicago outbreak of meningococcal disease that occurred in 2003 among a community of men who have sex with men. Isolates from this outbreak were identical to each other but distinct from the clone that caused a similar outbreak in Canada in 2001. PMID- 17728468 TI - Narrow-spectrum cephalosporin susceptibility testing of Escherichia coli with the BD Phoenix automated system: questionable utility of cephalothin as a predictor of cephalexin susceptibility. AB - The resistance of Escherichia coli to cephalothin was found to be overestimated when the Phoenix automated susceptibility system was used to determine resistance compared to reference broth microdilution, a finding that jeopardized the use of cephalexin for first-line treatment of urinary tract infections in children. In addition, using broth microdilution, we studied the accuracy of either cephalothin or cefazolin in predicting cephalexin susceptibility. In contrast to the recommendation of the Clinical Laboratory Standards Institute (CLSI), we found that cephalothin is not a reliable predictor of cephalexin susceptibility. Cefazolin performs no better in this role. We suggest that laboratories should consider testing and reporting cefazolin and cephalexin independently, according to clinical need. PMID- 17728469 TI - Microbiological evaluation of the new VITEK 2 Neisseria-Haemophilus identification card. AB - VITEK 2 is an automated identification system for diverse bacterial and fungal species. A new card (the Neisseria-Haemophilus [NH] card) for the identification of Neisseria spp., Haemophilus spp., and other fastidious gram-negative or gram variable microorganisms has been developed, but its performance in a routine clinical laboratory has not yet been evaluated. In this study, a total of 188 bacterial strains belonging to the genera Actinobacillus, Campylobacter, Capnocytophaga, Cardiobacterium, Eikenella, Gardnerella, Haemophilus, Kingella, Moraxella, and Neisseria were investigated. The NH card was able to identify 171 strains (91%) correctly without the need for extra tests; one strain (0.5%) was misidentified, and five strains (2.7%) could not be classified. Eleven strains (5.8%) were identified with a low level of discrimination, and simple additional tests were required to increase the correct-identification rate to 96.8%. The results were available within 6 h. Based on these results, the new VITEK 2 NH card appears to be a good method for the identification of diverse groups of fastidious organisms, which would otherwise require testing with multiple systems. However, more work is needed to evaluate the performance of VITEK 2 with regard to Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella bacteria because of the insufficient number of strains tested in this study. Moreover, further reduction of the detection time would be desirable. PMID- 17728470 TI - Clonal expansion and microevolution of quinolone-resistant Salmonella enterica serotype typhi in Vietnam from 1996 to 2004. AB - Salmonella enterica serotype Typhi clinical isolates (n = 91) resistant to nalidixic acid (Nal(r)) were collected from sporadic cases and minor outbreaks throughout Vietnam between 1996 and 2004. These isolates were typed and compared by four methods: Vi phage typing, PstI ribotyping, XbaI and SpeI pulsed-field gel electrophoresis (PFGE), and single-nucleotide polymorphism (SNP) analysis. The results indicated that 65% of the isolates were not typeable by Vi phage typing. In contrast, the ribotyping and, with more accuracy, the SNP analysis methods indicated that all Nal(r) isolates belonged to a single clone (ribotype 3a, haplotype H58) that was found previously and that largely consisted of plasmid encoded multidrug-resistant serotype Typhi isolates. PFGE demonstrated the occurrence of microevolution within this clone. We identified two major combined PFGE profiles: X1-S1 and X3-S6. X3-S6 predominated between 1996 and 2002 but was replaced by X1-S1 after 2002. Nevertheless, PFGE, with a Simpson's index of 0.78, was not considered an optimal discriminatory method for investigating typhoid fever outbreaks in Vietnam. The rate of quinolone resistance increased and the rate of multidrug resistance decreased during the study period. From 2002 to 2004, 80.6% of the isolates from South Vietnam were resistant only to Nal. The mechanism of Nal resistance in most of the isolates (94%) was a mutation in the quinolone resistance-determining chromosomal region of gyrA that led to the amino acid substitution Ser83Phe. No plasmid-located qnrA, qnrB, or qnrS was detected. PMID- 17728471 TI - Prolonged fecal shedding of hepatitis E virus (HEV) during sporadic acute hepatitis E: evaluation of infectivity of HEV in fecal specimens in a cell culture system. AB - To investigate the duration of fecal shedding and changing loads of hepatitis E virus (HEV) in feces and serum from patients with acute HEV infection, HEV RNA was quantitated in periodic serum and fecal specimens obtained from 11 patients with sporadic acute hepatitis E. All 11 patients had detectable HEV RNA in serum at admission, with the highest viral load being 1.9 x 10(3) to 1.7 x 10(7) copies/ml, and HEV viremia lasted until days 17 to 48 (mean, 28.3) after the onset of hepatitis. Even at the initial examination on days 10 to 29 (mean, 17.6), the HEV load in fecal supernatant was less than 5.7 x 10(4) copies/ml for 10 of the 11 patients, while for the remaining patient (patient 1) it was markedly high, 2.0 x 10(7) copies/ml on day 22. In addition, although HEV RNA in fecal supernatant continued to be positive until days 14 to 33 (mean, 22.4) for patients 2 to 11, that for patient 1 was detectable even on day 121. HEVs in fecal specimens obtained on days 22, 24, 26, 28, and 30, but not day 121, from patient 1 grew efficiently in PLC/PRF/5 cells, reaching the highest titer of up to 10(7) copies/ml in culture medium on day 50 postinoculation. The HEV genome recovered from patient 1 had 29 unique nucleotides that were not seen in any of the 25 reported HEV isolates of the same genotype over the entire genome, with six amino acid substitutions in the ORF1 protein. PMID- 17728472 TI - Use of a DNA microarray for simultaneous detection of antibiotic resistance genes among staphylococcal clinical isolates. AB - We developed a multiplex asymmetric PCR (MAPCR)-based DNA microarray assay for characterization of the clinically relevant antibiotic resistance genes leading to penicillin, methicillin, aminoglycoside, macrolide, lincosamide, and streptogramin B (MLS(B)) resistance in staphylococci. The DNA-based assay involves detection of specific conserved regions of the mecA, blaZ (methicillin and penicillin resistance), aac(6')-Ie-aph(2'') (aminoglycoside resistance), ermA and ermC genes (MLS(B) resistance), and the msrA gene (macrolide and streptogramin B resistance). The microarray uses a variable sequence region of the 16S rRNA gene to broadly differentiate between Staphylococcus aureus and other coagulase-negative staphylococci (CoNS). The performance of the microarray was validated with a total of 178 clinically important S. aureus and 237 CoNS isolates, with correlations of 100% for S. aureus to CoNS discrimination and more than 90% for antibiotic resistance between the genotypic analysis determined by the microarray and the phenotype determined by standard methods of species identification and susceptibility testing. The major discrepant results were 17 mecA-positive CoNS and 60 aac(6')-Ie-aph(2'')-positive CoNS isolates measured by microarray that were susceptible to the corresponding antibiotics based on disk diffusion assay. Overall, this microarray-based assay offers a simultaneous, fast (< or =5 h), and accurate identification of antibiotic resistance genes from a single colony, as well as species classification. Our extensive validation of the microarray suggests that it may be a useful tool to complement phenotypic susceptibility testing in clinical laboratories and to survey the spread of antibiotic resistance determinants in epidemiological studies. PMID- 17728473 TI - Characterization of a G11,P[4] strain of human rotavirus isolated in South Korea. AB - A novel human rotavirus strain, CUK-1, containing a G11 type combined with a P[4] type was isolated from a 1-year-old female patient with fever and severe diarrhea at Our Lady of Mercy Hospital in Incheon, South Korea. This CUK-1 strain showed the highest degree of nucleic acid similarity (98.7% and 93%) to G11 Dhaka6 and P[4] RV 5, respectively. This novel combined type of CUK-1 rotavirus strain (G11,P[4]) was uncovered from humans and is reported on here for the first time. PMID- 17728474 TI - Performance of a pneumolysin enzyme-linked immunosorbent assay for diagnosis of pneumococcal infections. AB - A pneumolysin-specific enzyme-linked immunosorbent assay (PLY-ELISA) for the detection of pneumolysin in urine was developed and evaluated in comparison with the commercially available Binax Now Streptococcus pneumoniae test (Binax, Portland, ME) for the diagnosis of pneumococcal infections. Assay sensitivity was evaluated using urine from 108 patients with culture-confirmed pneumococcal infections. In adults, the sensitivity and specificity of the PLY-ELISA were 56.6% and 92.2%, respectively. In children with nasopharyngeal pneumococcal carriage, PLY-ELISA and Binax Now S. pneumoniae test sensitivities were 62.5% and 87.5%, respectively, while specificities were 94.4% and 27.8%, respectively. In children with nonnasopharyngeal pneumococcal carriage, PLY-ELISA and Binax Now S. pneumoniae test sensitivities were 68.7% and 93.7%, respectively, and test specificities were 94.1% and 41.2%, respectively. The persistence of pneumolysin in urine of pneumococcal pneumonia patients decreased significantly after 4 to 6 days of treatment. Our data suggest that combining the high specificity of the PLY-ELISA with the high sensitivity of the Binax Now S. pneumoniae test would enable pneumococcal infections to be accurately diagnosed in children. PMID- 17728475 TI - Comparison between O serotyping method and multiplex real-time PCR to identify diarrheagenic Escherichia coli in Taiwan. AB - To compare the diarrheagenic Escherichia coli (DEC) identifications obtained between traditional O serotyping and modern virulence gene detection assays, we developed a multiplex real-time PCR assay by detecting six specific virulence genes for enteropathogenic E. coli (EPEC), enterohemorrhagic E. coli (EHEC), enterotoxigenic E. coli (ETEC), and enteroinvasive E. coli (EIEC). Among 261 clinical diarrheal stool samples, a total of 137 suspected DEC (sDEC) isolates were identified by the use of commercially available antisera. The most prevalent serogroups were O1 (12/137; 8.7%), O25 (9/137; 6.5%), and O44 (9/137; 6.5%). The specific virulence genes for the 137 sDEC isolates were analyzed by the multiplex real-time PCR assay. Fifteen (10.9%) of 137 isolates were confirmed to be true DEC strains, indicating that the serotypic markers did not correlate with the specific virulence genes. ETEC (66.7%) was the most prevalent, followed by EIEC (20%) and EPEC (13.3%). No EHEC strains were identified in the specimens. Four novel serotypes were found in the study: two in EPEC strains (O111:H9 and O63:H6) and two in EIEC strains (O63:H9 and O169:H9). In conclusion, the real-time PCR assay considerably reduces the high false-positive rate from the use of serotyping alone, and thus, it is suggested that serogrouping-based methods are inadequate for the identification of DEC isolates, although they are useful for the identification of a limited number of serogroups. In addition, ETEC, EPEC, and EIEC strains were present in 5.7% (15/261) of the diarrheal patients in northern Taiwan in 2006. PMID- 17728476 TI - First detection of G12 rotaviruses in newborns with neonatal rotavirus infection at all India Institute of Medical Sciences, New Delhi, India. AB - Rotavirus genotype G12 strains were detected for the first time among newborns with asymptomatic rotavirus infection (74% of 39 rotavirus strains isolated from the infected infants were genotype G12) in the nursery of the All India Institute of Medical Sciences during a period from 2005 to 2006. Sequence analysis of the VP7 genes from these neonatal strains indicated a high level of homology to other G12 strains reported worldwide, suggesting the recent emergence of these strains in humans. Such nosocomial infections of newborns represent a potential source of introduction of novel rotavirus serotypes into the community. PMID- 17728477 TI - Comparison between disk diffusion and microdilution methods for determining susceptibility of clinical fungal isolates to caspofungin. AB - We compared the caspofungin (CAS) susceptibility testing results generated by the disk diffusion (DD) assay with the results of the Clinical and Laboratory Standards Institute (CLSI) broth microdilution (BD) reference method for 106 yeast isolates. The isolates represented 11 different fungal species, including Candida albicans (n = 50), C. parapsilosis (n = 10), C. glabrata (n = 10), C. tropicalis (n = 10), C. guillermondii (n = 6), C. rugosa (n = 5), C. krusei (n = 5), C. kefyr (n = 2), C. pelliculosa (n = 2), Saccharomyces cerevisiae (n = 3), and Geotrichum candidum (n = 3). The DD assay was performed in supplemented Mueller-Hinton agar with CAS, which was tested at concentrations of 2, 10, and 25 mug per disk. MICs and inhibition zone diameters were evaluated at 24 and 48 h. In general, the results obtained by the DD assay correlated well with those obtained by the BD method. In particular, a significant correlation between methods was observed when CAS was used at concentration of 2 mug/disk at a reading time of either 24 or 48 h. PMID- 17728478 TI - Re: is throat screening necessary to detect methicillin-resistant Staphylococcus aureus colonization in patients upon admission to an intensive care unit? PMID- 17728479 TI - Mechanisms to assess Gram stain interpretation proficiency of technologists at satellite laboratories. AB - To address Gram stain interpretation proficiency in a satellite/centralized microbiology laboratory paradigm, two programs were devised. In quality assurance program 1, nonmicrobiology technologists at satellite laboratories were required to interpret standardized Gram-stained specimens of clinical material prepared by an experienced microbiologist at a central laboratory. In quality assurance program 2, clinical Gram stains prepared and read by the satellite laboratorians were reviewed by experienced microbiologists at the central laboratory. Satisfactory performance (94%) was achieved in quality assurance program 1. In contrast, quality assurance program 2 had a significantly lower overall performance (89%; P < 0.0001) due to poorer identification of host cells (93%) and bacteria (84%). A variety of intervention mechanisms, including continuous monitoring, resulted in overall performance improvement (P < or = 0.006). While a technologist challenge has educational merit, having a microbiologist review previously read slides is a better indicator of the technologist's Gram stain interpretation proficiency. PMID- 17728480 TI - Pregnancy-associated plasma protein-a levels are related to glycemic control but not to lipid profile or hemostatic parameters in type 2 diabetes. PMID- 17728481 TI - Influence of flickering light on the retinal vessels in diabetic patients. AB - OBJECTIVE: Stimulation of the retina with flickering light increases retinal vessel diameters in humans. Nitric oxide is a mediator of the retinal vasodilation to flicker. The reduction of vasodilation is considered an endothelial dysfunction. We investigated the response of retinal vessels to flickering light in diabetic patients in different stages of diabetic retinopathy. RESEARCH DESIGN AND METHODS: We studied 53 healthy volunteers, 68 type 1 diabetic patients, and 172 type 2 diabetic patients. The diameter of retinal vessels was measured continuously online with the Dynamic Vessel Analyzer (DVA). Diabetic retinopathy was classified using Early Treatment Diabetic Retinopathy Study criteria. Changes in vasodilation are expressed as percent change over baseline values. RESULTS: After adjustments for age, sex, and antihypertensive treatment, the response of retinal arterioles to diffuse luminance flicker was significantly diminished in patients with type 1 diabetes compared with healthy volunteers. The vasodilation of retinal arterioles and venules decreased continuously with increasing stages of diabetic retinopathy. The retinal arterial diameter change was 3.6 +/- 2.1% in the control group, 2.6 +/- 2.5% in the no diabetic retinopathy group, 2.0 +/- 2.7% in the mild nonproliferative diabetic retinopathy (NPDR) group, 1.6 +/- 2.2% in the moderate NPDR group, 1.8 +/- 1.9% in severe NPDR group, and 0.8 +/- 1.6% in proliferative diabetic retinopathy group. CONCLUSIONS: Flicker responses of retinal vessels are abnormally reduced in diabetic patients. This decreased response deteriorated with increasing stages of retinopathy. The response was already reduced before clinical appearance of retinopathy. The noninvasive testing of retinal autoregulation with DVA might prove to be of value in early detection of diabetic vessel pathological changes. PMID- 17728482 TI - Trends in hospitalizations for diabetes among children and young adults: United States, 1993 2004. AB - OBJECTIVE: The purpose of this study was to examine national trends in hospitalizations associated with diabetes for U.S. children and young adults. RESEARCH DESIGN AND METHODS: The study included hospital discharges for individuals aged 0-29 years with a diagnosis of diabetes (250.xx) in the Nationwide Inpatient Sample (1993-2004). Outcomes were weighted, nationally representative estimates of the frequency of population-adjusted hospital discharges and hospital charges (2004 $U.S.). RESULTS: Among individuals aged 0 29 years, population-adjusted rates of hospitalizations associated with diabetes over the 12-year period increased by 38% (99.1 of 100,000 in 1993 and 136.4 of 100,000 in 2004; P < 0.001 for curvilinear trend). Age-specific increases in annual hospitalizations for diabetes occurred primarily among individuals aged 20 24 years (152.6 of 100,000 in 1993 and 222.2 of 100,000 in 2004) and 25-29 years (224.9 of 100,000 in 1993 and 331.2 of 100,000 in 2004). Trends in hospitalizations among younger individuals showed no significant patterns. Hospitalization rates were consistently higher for females than for males, with a greater rate of increase for females (42%) than for males (29%) (P < 0.001). Inflation-adjusted total charges for diabetes hospitalizations increased 130%, from $1.05 billion in 1993 to $2.42 billion in 2004. CONCLUSIONS: The number of young adults hospitalized with diabetes in the U.S. has increased significantly over the last decade. Sex-specific differences in hospitalization rates and trends in obesity among U.S. children may amplify future trends in diabetes hospitalizations and corresponding rapid growth in associated health care expenditures. PMID- 17728483 TI - Diabetes or impaired glucose tolerance: does the label matter? PMID- 17728484 TI - New treatment approaches: integrating new media in the treatment of war and torture victims. AB - The diagnostic process and treatment of victims of war and torture is associated with a number of difficulties. This article will provide an overview of three different approaches on how the new media may be integrated into the treatment of survivors of torture and war to face some of the challenges. Illiteracy is a common problem and makes it difficult to apply standardized psychological assessment procedures. Also, the majority of survivors of torture and war do not have access to any psychotherapeutic treatment due to geographical limitations or limitations concerning psychotherapeutic treatment capacity. Furthermore, chronic psychological disorders such as (complex) Posttraumatic Stress Disorder (PTSD) are often seen with comorbid chronic pain disorders, which present a therapeutic challenge. The Treatment Center for Torture Victims, Berlin, in cooperation with the University of Zurich, developed a number of approaches to address these challenges: 1) MultiCASI - to standardize the diagnostic process an audiovisual diagnostic tool was developed which allows illiterate individuals to answer standardized psychological questionnaires whithout the help of interpreters; 2) A virtual treatment center for posttraumatic stress disorder for traumatized patients in Iraq and other Arab speaking postconflict countries; 3) Utility of Biofeedback (BF) in chronic (somatoform) pain and in traumatized patients: to address the chronic pain syndrome presented by most survivors, a biofeedback supported cognitive-behavioral therapy approach was developed and successfully tested in a pilot study. PMID- 17728485 TI - Psychological evaluation of asylum seekers as a therapeutic process. AB - Torture survivors are often reluctant to tell their stories. They typically make every effort to forget this painful, traumatic experience. Often they do not share with family, friends or healthcare professionals the fact that they have been beaten, raped or subjected to electrical shocks and other terrors. Talking means retrieving memories, triggering the feelings and emotions that accompanied the torture itself. Furthermore, refugee torture survivors feel that people won't understand or believe their experiences. However, survivors who escape their country may need to reveal their torture experience as they apply for asylum in the host country. When they prepare for the asylum process, it may well be the first time that they talk about the torture. Mental health professionals are often called upon to evaluate survivors and prepare affidavits for the asylum process, documenting the effects of torture. This creates a unique and priviliged opportunity to help survivors to address the devastating consequences of torture. Winning asylum is essential to recovery for a torture survivor in a country of refuge. Psychological evaluations of the consequences of torture can present information and evidence to asylum adjudicators which significantly increases understanding of the survivors' background and experiences as well as their manner of self-presentation in the courtroom or interview. They can empower the torture survivor to present his/her experiences more fully and confidently. Even apart from winning asylum, the process of the evaluation has many potential benefits for the survivor's emotional well-being. This includes helping the survivor understand the necessity of telling the story, illuminating the often poorly perceived link between current emotional suffering and past torture, facilitating the development of cognitive and emotional control, and healing the wounds of mistrust, humiliation, marginalization and fear. PMID- 17728486 TI - Treatment of torture survivors - influences of the exile situation on the course of the traumatic process amd therapeutic possibilities. AB - Traumatized refugees often suffer from complex posttraumatic disorders with a high tendency of chronicity. This is due to severe and often repeated traumatization in the course of political persecution on one hand and uprooting and ongoing stress caused by leaving their home country and society and living under an adverse situation in exile on the other hand. This article shows how positive and negative factors going along with migration interfere with the course of the traumatic process and the therapeutic possibilities and how the therapeutic process can be adjusted to the situation. PMID- 17728487 TI - The right to reparations for acts of torture: what right, what remedies? PMID- 17728489 TI - The Convention Against Torture and other cruel, inhuman or degrading treatment or punishment (CAT) - articles 22 and 20. PMID- 17728488 TI - Forensic medical examination of victims of trafficking in human beings. AB - Trafficking in human beigns (THB) is recognized as a global public health issue as well as a violation of human rights. Trafficking has been identified to be associated with several health risks including psychological trauma, injuries from violence, and substance misuse. Public and media reports suggest that the morbidity and mortality associated with trafficking are substantial. The need of medico-legal healthcare for THB victims is being neglected. Forensic medical examination, as specific intervention, is a highly desirable element of ermegency health care provided for victims of tracking. Acting in such a way, the investigation should establish the facts related to the allegatation of trafficking, thereby assisting in identifying those responsible, but also contributing to the procedures designed to obtain redress for the victims. Local anti-trafficking policies and interventions, however, have not acknowledged these needs. Therefore, the agenda of anti-trafficking policies needs to be redrawn to include forensic medical assessment of victims for legal purposes. PMID- 17728490 TI - The Convention Against Torture and other cruel, inhuman or degrading treatment or punishment (CAT)/Optional Protocol to the Convention Against Torture and Other Cruel, Inhuman or Degrading Treatment or Punishment (OPCAT). PMID- 17728492 TI - Integrating rehabilition of torture victims into the public health of Iraq. AB - For the last three decades torture has been highly prevalent in Iraq. Surveys indicate that close to 50% of households have family members who have been tortured. The traumas of two subsequent wars further add to the traumatisation of the population as does the persistent violence. Re-traumatisation makes healing difficult. As a result trauma-related disorders are likely to be the number one public health problem in Iraq. In December 2004, the author was tasked with the responsibility of planning and implementing rehabilitation activities for victims of torture in Iraq. Basra, in southern Iraq, was chosen as the place for the first clinical treatment and rehabilitation Centre, the Al-Fuad Centre for Rehabilitation of Torture Victims (FRCT). The Centre was to function as a training institution for the entire country. In a effort to bridge the gap between vast needs and limited resources, the Centre has begun applying a public health perspective, which means to develop its work in relation to the concepts of illness prevention and health promotion. Treatment and rehabilitation, i.e the secondary and tertiary levels of prevention, can be multiplied through the training of professionals who will be able to establish treatment facilities in new areas of Iraq. By training GPs, psychiatrists and physicians and by expanding FRCT services to victims' families, signs and symptoms of trauma can be addressed at early stages of disorder and long-term illness averted. Human Rights advocacy and legal work at the Centre will address the primary level of prevention through diminishing human rights abuses. Finally, engaging in the reconstruction of the civil society alongside other NGOs and government authorities is to build democracy, which is a cornerstone of health promotion, especially so when the illness panorama is related to violence. PMID- 17728491 TI - Dance/movement therapy approaches to fostering resilience and recovery among African adolescent torture survivors. AB - Dance/movement therapy (DMT) interventions, if designed to promote cultural relevance and community ownership, may enhance healing among African adolescent survivors of war and organised violence. The author posits a theoretical rationale for body movement-based approaches to psychosocial rehabilitation, and offers DMT's holism as evidence of transcultural applicability. Two distinct DMT iniatives with this population are discussed in terms of theoretical assumptions, implementation, and outcomes. Both efforts afforded creative means for discharging aggression and restoring interpersonal connection. The first of these programes engaged a community of South Sudanese refugee youths, resettled to the U.S., in a series of gatherings for traditional dancing and drumming that reconstituted a central culture-of-origin ritual. Anectodal evidence supports this psychosocial intervention's emphasis on group cohesion as a vehicle with both preventive and reparative capacities. Also a series of DMT groups with youths in Sierra Leone. All organized several years post-conflict, these interventions involved applying the DMT modality within a framework of Western psychotherapeutic conventions described in a series of groups with youths, all organized several years post-conflict, is presented. Programe evaluation revealed a drop in average symptom expression among a group comprised of former boy combatants who reported continual reduction in symptoms of anxiety, depression, intrusive recollection, elevated arousal, and aggression. The group's teenage males joined actively in improvisatory dancing and in other structured creative exercices. Theese former child soldiers later elected to demonstrate their wartime experiences through public presentation of a role-play. A report on this event illustrates the success of the process in overcoming stigma and enabling meaningful community reintegration. Thus, whether introduced in refuge or post conflict, DMT approaches are shown to embody revitalizing psychosocial support in the aftermath of massive violence. PMID- 17728493 TI - Sexual violence against women: psycho-juridical approach. AB - In December 1982, the Peruvian government declared emergency zones in the country, giving control to the armed forces who applied operational plans aimed at eliminating guerrilla violence. The report of the Truth and Reconciliation Commission conlcudes there is evidence that sexual violence was a generalized practice quietly tolerated by the security forces, and in some cases, openly permitted by immediate superiors. The violence took place during military operations, but also certain army and police facilities. This practice may have taken place in a systematic way, linked with the repression of guerrilla violence, in certain provinces of the regions of Ayacucho, Huancavelica and Apurimac. The same report argues "one of the most affected groups in a context of armed conflict is women, who suffer not only the general effects of this type of situation, but also numerous violations of their rights by the mere fact that they are women". PMID- 17728494 TI - Nuclear medicine for all the world--from molecular imaging to molecular medicine. PMID- 17728495 TI - The effect of dialysis membrane flux on amino acid loss in hemodialysis patients. AB - We examined whether high flux membranes (HF) may induce a greater loss of amino acids compared to low flux membranes (LF). Ten hemodialysis patients participated in this study. Pre- and post-hemodialysis plasma amino acid profiles were measured by reverse-phase high pressure liquid chromatography for both HF and LF. We measured the dialysate amino acid losses during hemodialysis. The reduction difference for plasma total amino acid (TAA), essential amino acid (EAA), and branch chained amino acid (BCAA) was not significantly different in comparisons between the two membranes. (HF vs. LF; TAA 66.85 +/- 30.56 vs. 53.78 +/- 41.28, p=0.12; EAA 14.79 +/-17.16 vs. 17.97 +/- 28.69, p=0.12; BCAA 2.21 +/- 6.08 vs. 4.16 +/- 10.98 mg/L, p=0.13). For the HF, the reduction in plasma amino acid levels for TAA and EAA were statistically significant. Although it was not statistically significant, the dialysate losses of BCAA were greater than the reduction in plasma (plasma reduction vs. dialysate loss; HF 2.21 +/- 6.08 vs. 6.58 +/- 4.32, LF 4.16 +/- 10.98 vs. 7.96 +/- 3.25 mg/L). HF with large pores and a sieving coefficient do not influence dialysate amino acid losses. Hemodialysis itself may influence the dialysate amino acid losses and may have an effect on protein metabolism. PMID- 17728496 TI - Associations between sympathetic activity, plasma concentrations of renin, aldosterone, and parathyroid hormone, and the degree of intractability of blood pressure control in modialysis patients. AB - This study was designed to examine how such factors as hemodialysis parameters, body mass index, renin and aldosterone concentrations, sympathetic nervous activity, and parathyroid hormone concentrations are associated with the control of hypertension in hemodialysis patients. Hemodialysis patients (n=114) were grouped into four categories. Group 1 had normal BP without antihypertensive medication. Group 2 needed one antihypertensive drug, Group 3 needed combination of two or three categories of antihypertensive drugs without minoxidil. Group 4 needed more than three categories of antihypertensive drugs including minoxidil. Parathyroid hormone, beta2-microglobulin, renin and aldosterone, epinephrine, norepinephrine, and hemodialysis parameters were measured. The fractional clearance of urea as Kt/V urea was significantly lower in Group 3 and Group 4 than in Group 2 (p<0.01). Concentrations of parathyroid hormone were significantly higher in Group 4 than the other groups (p<0.01). Pre-hemodialysis norepinephrine concentrations were significantly higher in Group 4 than the other groups (p<0.05). Traditional factors associated with hypertension did not seem to be relevant to the degree of hypertension in hemodialysis patients in the present study. In conclusion, poor Kt/V urea, elevated parathyroid hormone concentrations, and elevated concentrations of plasma norepinephrine seemed to be the factors that might be associated with control of hypertension in hemodialysis patients. PMID- 17728497 TI - MCP-1 and RANTES polymorphisms in Korean diabetic end-stage renal disease. AB - Macrophage infiltration has been observed in the renal biopsy specimens of diabetic nephropathy (DN), and hyperglycemic state stimulates the renal expression of RANTES (regulated upon activation, normal T-cell expressed and secreted) and MCP- 1 (monocyte chemoattractant protein-1). Upregulation of RANTES and MCP-1 with infiltrating macrophages may play a crucial role in the development and progression of DN. Genetic polymorphisms of RANTES and its receptors were reported to be independent risk factors for DN. We genotyped single nucleotide polymorphism (SNPs) in the MCP-1 G-2518A, CCR2 G46295A, RANTES C-28G and G-403A in 177 diabetic end-stage renal disease (ESRD) patients and 184 patients without renal involvement (controls) in order to investigate the effects of these SNPs on DN in Korean patients with type 2 DM. There were no differences in the frequencies of SNPs and the distribution of haplotypes of RANTES promoter SNPs between two groups. In conclusion, there were no associations of MCP-1, CCR2 and RANTES promoter SNPs with diabetic ESRD in Korean population. Prospective studies with clearly-defined, homogenous cohorts are needed to confirm the effect of these genetic polymorphisms on DN. PMID- 17728498 TI - Sulfonylurea therapy in two Korean patients with insulin-treated neonatal diabetes due to heterozygous mutations of the KCNJ11 gene encoding Kir6.2. AB - Permanent neonatal diabetes (PND) is a rare form of diabetes characterized by insulin-requiring hyperglycemia diagnosed within the first three months of life. In most cases, the causes are not known. Recently, mutations in the KCNJ11 gene encoding the Kir6.2 subunit of the ATP-sensitive K+ channel have been described in patients with PND. We report the first two Korean cases with PND due to a lysineto- arginine substitution at position 170 (K179R) and a valine-to methionine substitution at position 59 (V59M) mutations of KCNJ11 encoding Kir6.2, respectively. After several years of insulin therapy, these patients were managed by oral glibenclamide therapy at a daily dose of 0.8-0.9 mg/kg. Their basal c-peptide levels increased after one week of glibenclamide therapy, and one month later, the insulin and c-peptide levels were in the normal ranges without any episodes of hyper- or hypoglycemia. These cases demonstrate that oral sulfonylurea may be the treatment of choice in PND patients with KCNJ11 mutations even at a young age. PMID- 17728499 TI - Diagnostic value of galectin-3, HBME-1, cytokeratin 19, high molecular weight cytokeratin, cyclin D1 and p27(kip1) in the differential diagnosis of thyroid nodules. AB - The distinction between benign and malignant thyroid tumors is critical for the management of patients with thyroid nodules. We applied immunohistochemical staining for galectin-3, HBME-1, cytokeratin 19 (CK19), high molecular weight cytokeratin (HMWCK), cyclin D1 and p27(kip1) in 295 thyroid lesions to determine their diagnostic accuracy. The expression of all markers was significantly associated with differentiated thyroid carcinoma (DTC). The sensitivity for the diagnosis of DTC was 94.7% with galectin-3, 91.3% with HBME-1, and 90.3% with CK19. The specificities of these markers were 95.5%, 69.7%, and 83.1%, respectively. Combining these markers, co-expression of galectin-3 and CK19 or galectin-3 and HBME-1 was seen in 93.2% of carcinomas but in none of the benign nodules. Comparing follicular variant of papillary carcinoma (FVPC) with follicular carcinoma (FC), the expression of galectin-3, CK19, and HMWCK was significantly higher in FVPC. When comparing FC with FA, the expression of galectin-3 and HBME-1 was significantly higher in FC. These results suggest that 1) galectin-3 is a useful marker in the distinction between benign and malignant thyroid tumors, 2) the combined use of HBME-1 and CK19 can increase the diagnostic accuracy, and 3) the use of CK19 and HMWCK can aid in the differential diagnosis between PC and FC. PMID- 17728500 TI - Cardiac autonomic function evaluated by the heart rate turbulence method was not changed in obese patients without co-morbidities. AB - Obese subjects are more prone to sudden deaths and arrhythmias than non-obese subjects. Heart rate turbulence (HRT) impairment reflects cardiac autonomic dysfunction, in particular impaired baroreflex sensitivity and reduced parasympathetic activity. Our aim was to evaluate the cardiac autonomic function in obesity by the HRT method. Ninety obese subjects and 112 healthy subjects were included in the study. Twenty-four hours ambulatory electrocardiograms were recorded and Holter recordings were analyzed. HRT parameters, turbulence onset (TO) and turbulence slope (TS), were calculated with HRT View Version 0.60-0.1 software program. HRT were calculated in 43 obese and 43 control subjects who had at least one ventricular premature beat in their Holter recordings. We excluded 47 obese patients and 69 control subjects who showed no ventricular premature beats in their Holter recordings from the statistical analysis. There were no significant differences in TO and TS between obese and control subjects (TO obese: -1.6 +/- 2.2%, TO control: -2.1 +/- 2.6%, p>0.05; TS obese: 8.2 +/- 5.2, TS control: 10.1 +/- 6.7, p>0.05, respectively). HRT parameters seem to be normal in obese patients without comorbidities. PMID- 17728501 TI - Decreased left ventricular torsion and untwisting in children with dilated cardiomyopathy. AB - The purpose of this study was to analyze left ventricular (LV) torsion and untwisting, and to evaluate the correlation between torsion and other components of LV contraction in children with dilated cardiomyopathy (DCM). Segmental and global rotation, rotational rate (Vrot) were measured at three levels of LV using the two dimensional (2D) speckle tracking imaging (STI) method in 10 DCM patients (range 0.6-15 yr, median 6.5 yr, 3 females) and 17 age- and sex-matched normal controls. Global torsion was decreased in DCM (peak global torsion; 10.9 +/- 4.6 degrees vs. 0.3 +/- 2.1 degrees , p<0.001). Loss of LV torsion occurred mainly by the diminution of counterclockwise apical rotation and was augmented by somewhat less reduction in clockwise basal rotation. In DCM, the normal counterclockwise apical rotation was not observed, and the apical rotation about the central axis was clockwise or slightly counterclockwise (peak apical rotation; 5.9 +/- 4.1 degrees vs. -0.9 +/- 3.1 degrees , p<0.001). Systolic counterclockwise Vrot and early diastolic clockwise Vrot at the apical level were decreased or abolished. In DCM, decreased systolic torsion and loss of early diastolic recoil contribute to LV systolic and diastolic dysfunction. The STI method may facilitate the serial evaluation of the LV torsional behavior in clinical settings and give new biomechanical concepts for better management of patients with DCM. PMID- 17728502 TI - Netrin inhibits regenerative axon growth of adult dorsal root ganglion neurons in vitro. AB - Netrin is a neuronal guidance molecule implicated in the development of spinal commissural neurons and cortical neurons. The attractive function of netrin requires the receptor, Deleted in Colorectal Cancer (DCC), while the receptor Unc5h is involved in the repulsive action of netrin during embryonic development. Although the expression of netrin and its receptor has been demonstrated in the adult nervous system, the function of netrin in adult neurons has not yet been elucidated. Here, we show that netrin treatment inhibited neurite outgrowth of adult dorsal root ganglion (DRG) neurons in explant and dissociated cultures. In addition, unc5h1-3 mRNAs, but not the dcc mRNA, are abundantly expressed in the adult DRG. An in situ hybridization study demonstrated that unc5h mRNAs were expressed in DRG neurons. This finding indicates that netrin/Unc5h signaling may play a role in the neurite outgrowth of adult DRG neurons and that netrin may be involved in the regulation of peripheral nerve regeneration. PMID- 17728503 TI - Postoperative changes in paraspinal muscle volume: comparison between paramedian interfascial and midline approaches for lumbar fusion. AB - In this study, we compared the paramedian interfascial approach (PIA) and the traditional midline approach (MA) for lumbar fusion to determine which approach resulted in the least amount of postoperative back muscle atrophy. We performed unilateral transforaminal posterior lumbar interbody fusion via MA on the symptomatic side and pedicle screw fixation via PIA on the other side in the same patient. We evaluated the damage to the paraspinal muscle after MA and PIA by measuring the preoperative and postoperative paraspinal muscle volume in 26 patients. The preoperative and postoperative cross-sectional area, thickness, and width of the multifidus muscle were measured by computed tomography. The degree of postoperative paraspinal muscle atrophy was significantly greater on the MA side than on the contralateral PIA side (-20.7% and -4.8%, respectively, p<0.01). In conclusion, the PIA for lumbar fusion yielded successful outcomes for the preservation of paraspinal muscle in these 26 patients. We suggest that the success of PIA is due to less manipulation and retraction of the paraspinal muscle and further studies on this technique may help confirm whether less muscle injury has positive effects on the long-term clinical outcome. PMID- 17728504 TI - Carbohydrate-deficient transferrin as a marker of heavy drinking in Korean males. AB - This study was performed to evaluate the usefulness of carbohydrate-deficient transferrin (CDT) as a marker of heavy drinking in Korean males. The subjects (143 Korean males) were classified into 2 groups according to the amount of drinking, moderate drinkers (72 individuals) who drank 14 drinks or less per week and heavy drinkers (71 individuals) who drank more than 14 drinks per week. Using %CDT, gamma glutamyl transferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) as clinical markers for heavy drinking, sensitivity, specificity, positive and negative predictive values were investigated. Sensitivities of %CDT, GGT, AST, and ALT were 83.1%, 67.6%, 52.1% and 46.5%, respectively. Specificities were 63.9%, 45.8%, 72.2%, and 54.2%, respectively. Positive predictive values were 69.4%, 55.2%, 64.9%, and 50.0% respectively. Negative predictive values were 79.3%, 58.9%, 60.5%, and 50.6% respectively. The areas under the receiver operating characteristic curve (95% confidence interval) for %CDT, GGT, AST, and ALT were 0.823 (0.755-0.891), 0.578 (0.484-0.673), 0.622 (0.528-0.717), and 0.516 (0.420-0.613), respectively. CDT is considered as the most reliable marker for detecting heavy drinking in Korean males. PMID- 17728505 TI - Electrophysiologic assessment of central auditory processing by auditory brainstem responses in children with autism spectrum disorders. AB - In addition to aberrant features in the speech, children with Autism Spectrum Disorder (ASD) may present unusual responses to sensory stimuli, especially to auditory stimuli. We investigated the auditory ability of children with ASD by using Auditory Brainstem Responses (ABR) as they can directly judge both hearing status and the integrity of auditory brainstem pathways. One hundred twenty-one children (71: ASD; M 58/ F 13, mean age; 41.8 months, 50: control group; M 41/ F 9, mean age; 38 months) were included in the study. As compared with the values in the control group, the latency of wave V, wave I-V, and wave III-V inter-peak latencies were significantly prolonged (p<0.05) in the ASD group. The findings indicate that children with ASD have a dysfunction or immaturity of the central auditory nervous system. We suggest any children with prolonged III-V inter-peak latencies, especially high functioning children should be further evaluated for central auditory processing to set up a more appropriate treatment plan. PMID- 17728506 TI - Ultrasonographic findings of the shoulder in patients with rheumatoid arthritis and comparison with physical examination. AB - The objectives of this study were: 1) to identify the ultrasonographic (US) abnormalities and 2) to compare the findings of physical examination with US findings in rheumatoid arthritis (RA) patients with shoulder pain. We studied 30 RA patients. Physical examination was performed systemically as follows: 1) area of tenderness; 2) range of passive and active shoulder motion; 3) impingement tests; 4) maneuvers for determining the location of the tendon lesions. US investigations included the biceps, the supraspinatus, infraspinatus, and subscapularis tendons; the subacromial-subdeltoid bursa; and the glenohumeral and acromioclavicular joints. Thirty RA patients with 35 painful and 25 non-painful shoulders were examined. The range of motion affected the most by shoulder pain was abduction. The most frequent US finding of shoulder joint was effusion in the long head of the biceps tendon. Among the rotator cuff tendons, subscapularis was the most frequently involved. Tendon tear was also common among non-painful shoulders. Physical examination used for the diagnosis of shoulder pain had low sensitivity and specificity for detecting abnormalities in the rheumatoid shoulder joint. In conclusion, US abnormalities showed frequent tendon tears in our RA patients. Physical examination had low sensitivity and specificity for detecting rotator cuff tear in the rheumatoid shoulder joint. PMID- 17728507 TI - Lack of association between matrix metalloproteinase 8 promoter polymorphism and bronchiectasis in Koreans. AB - The observation that human matrix metalloproteinase (MMP)-8 is over-expressed in ectatic bronchi in patients with bronchiectasis suggests that polymorphisms altering the expression of MMP-8 may contribute to the susceptibility to development of bronchiectasis. We evaluated the association between the presence of bronchiectasis in a Korean population and two single nucleotide polymorphisms (SNPs) (-799C/ T and -381A/G) on the promoter region of the MMP-8 gene that are reported to alter the promoter activity and thereby the gene expression. Genotyping through polymerase chain reaction (PCR) and subsequent automatic sequencing was done in 167 patients with bronchiectasis and their age-, sex matched healthy controls to reveal that only -799C/T is polymorphic among Koreans. In the patient group with bronchiectasis, the frequency of -799C/C, C/T, and T/T genotypes were 41.9%, 49.7%, and 8.4%, respectively. A similar distribution was observed in the control group: C/C (49.7%), C/T (43.1%), and T/T (7.2%) (p=0.36). In subgroup analysis, no significant difference was observed among the patients according to; the extent of disease (p=0.76), colonization of microorganisms (p=0.56), or association of mycobacteria (p=0.17). From these results, we conclude that -799C/T on the promoter region of MMP-8 lacks association with development of bronchiectasis in Koreans. PMID- 17728508 TI - Comparison of the real-time nucleic acid sequence-based amplification (RTi-NASBA) with conventional NASBA, and galactomannan assay for the diagnosis of invasive aspergillosis. AB - We compared a real time-nucleic acid sequence-based amplification (RTi-NASBA) with conventional NASBA, galactomannan enzyme immunosorbent assay (GMEIA), and Mycology Study Group of the European Organization for Research and Treatment of Cancer (EORTC/MSG) criteria for the diagnosis of invasive aspergillosis (IA). From May 2004 to May 2005, blood samples (314 in total) were collected twice a week from 78 patients with hematologic diseases during neutropenic fever after chemotherapy or hematopoietic stem cell transplantation. Results were compared with each other on the basis of EORTC/ MSG criteria. The cutoff of conventional NASBA was set to be 3.5; GM 0.5; RTi-NASBA, 20% above the negative control. There were 22 patients with IA (7 probables and 15 possibles) and 56 patients with nonfungal infection. The Kappa statistic for RTi-NASBA versus conventional NASBA was 0.80 (0.66-0.82; p<0.001) indicating that there was fairly good accordance between two tests. RTi-NASBA showed sensitivity 0.96, specificity 0.43, positive- and negative-predictive value 0.40 and 0.96, respectively. GM showed good specificity (0.98), while the sensitivity (0.45) was poor. When we use the combination of GM with either of two NASBAs, the sensitivity was improved up to 100%. In conclusion, RTi-NASBA could be a good alternative to the conventional one for the screening of IA. PMID- 17728509 TI - Drug resistance rates of Mycobacterium tuberculosis at a private referral center in Korea. AB - The goals of this study were to identify first-line drug resistance in new and previously treated tuberculosis (TB) cases and to determine risk factors for multidrug resistant TB (MDR-TB) at a private referral center in Korea. All patients with culture confirmed pulmonary TB over a 2-yr period between July 2002 and June 2004 were prospectively included in this study. In total, 637 patients were included; 512 (80.4%) were new cases, and 125 (19.6%) were previously treated cases. Resistance to at least one first-line drug was identified in 11.7% of new cases and 41.6% of previously treated cases. MDR-TB was detected in 3.9% of new cases and 27.2% of previously treated cases. The proportion of extensively drug-resistant TB among MDR-TB patients was 16.7% (9/54). Factors associated with MDR-TB included age under 45 yr, previous TB treatment, and the presence of cavitation on chest radiography. Rates of first-line drug resistance are high, particularly in previously treated patients, in the private sector in Korea. This underscores the need for an improved control program, coupled with early diagnosis of MDR-TB, to reduce the spread and development of resistance. PMID- 17728510 TI - Analysis of methicillin resistance among Staphylococcus aureus blood isolates in an emergency department. AB - The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) has become of great concern in both hospital and community settings. To evaluate the prevalence and risk factors for methicillin resistance among Staphylococcus aureus, blood isolates in our Emergency Department (ED) were collected. All patients with S. aureus bacteremia (SAB) who presented to the ED from January 2000 to August 2005 were included, and a retrospective study was performed. A total of 231 patients with SAB were enrolled (median age, 59 yr; M:F, 125:106). Among these patients, methicillin-resistant strains accounted for 27.3% (63 patients). Catheter-related infection was the most frequent primary site of SAB (39.0%), followed by skin and soft tissue infection (16.5%). In multivariate analysis, recent surgery (OR, 3.41; 95% CI, 1.48-7.85), recent hospitalization (2.17; 1.06-4.62), and older age (> or =61 yr) (2.39; 1.25-4.57) were independently associated with the acquisition of methicillin-resistant strains. When antimicrobial therapy is considered for the treatment of a patient with suspected SAB, clinicians should consider obtaining cultures and modifying empirical therapy to provide MRSA coverage for patients with risk factors: older age, recent hospitalization, and recent surgery. PMID- 17728511 TI - Survival rate changes in neonates with congenital diaphragmatic hernia and its contributing factors. AB - The purpose of this study was to demonstrate survival rate changes after the introduction of inhaled nitric oxide (iNO) therapy, and to identify the factors that influence these changes in neonates with a congenital diaphragmatic hernia (CDH) at a single center. A total of 48 neonates were divided into two groups based on the time of admission, i.e., into period I (P1; n=17; before the introduction of iNO therapy) and period II (P2; n=31; after the introduction of iNO therapy). Survival rates of the 48 neonates showed a tendency to increase from 53% during P1 to 77% during P2, but without a statistical significance, but a significant difference was found between survival rates during the two periods after adjusting for initial clinical characteristics, when the postoperative survival rate increased significantly from 69% for P1 to 100% for P2. The mean duration of preoperative respiratory management was significantly longer for P2 than for P1. Seven of 12 patients who received preoperative iNO therapy due to persistent pulmonary hypertension or refractory preductal hypoxemia in P2 survived after operation. We speculate that a management strategy based on iNO therapy and delayed operation, rather than differences between the initial clinical characteristics of the two study groups, might partially contribute to the observed improvements in postoperative and overall survival rates in neonates with CDH. PMID- 17728513 TI - Genetic analysis of three Korean patients with clinical features of Ehlers-Danlos syndrome type IV. AB - Ehlers-Danlos syndrome (EDS) is a hereditary disorder of the connective tissue. EDS type IV (EDS IV), the vascular type of the disease, is characterized by easy bruising, thin skin with visible veins, and spontaneous rupture of the large arteries, uterus, or bowel. EDS IV is caused by mutations in the gene for type III procollagen (COL3A1). However, recent studies suggest that the causative mutation of EDS IV is not homogeneous. We report our experience with three patients presenting with clinical features of type IV EDS. A 48-yr-old woman presented with acute aortic dissection (patient 1) and 36-yr-old and 21-yr-old women presented with carotidcavernous fistula (patients 2 and 3, respectively). All three patients bruised easily. Two patients (patients 1 and 3) had thin transparent skin with visible veins. Genetic analysis of COL3A1 revealed a Gly732Val (c.2195G>T) mutation in patient 1 and a duplication of 15 base pairs (c.3221_3235dup) which resulted in an interposition of five amino acids (p.Gly1074_Pro1078dup) in patient 2. However, no mutations were observed in COL3A1 or transforming growth factor beta receptors 1 and 2 in patients 3, which might be either due to a deletion of single or multiple exons in the COL3A1 gene or due to a genetic heterogeneity. This is the first report of genetically confirmed cases of EDS IV in Korea. PMID- 17728512 TI - The efficacy of the COMFORT scale in assessing optimal sedation in critically ill children requiring mechanical ventilation. AB - Sedation is often necessary to optimize care for critically ill children requiring mechanical ventilation. If too light or too deep, however, sedation can cause significant adverse reactions, making it important to assess the degree of sedation and maintain its optimal level. We evaluated the efficacy of the COMFORT scale in assessing optimal sedation in critically ill children requiring mechanical ventilation. We compared 12 month data in 21 patients (intervention group), for whom we used the pediatric intensive care unit (PICU) sedation protocol of Asan Medical Center (Seoul, Korea) and the COMFORT scale to maintain optimal sedation, with the data in 20 patients (control group) assessed before using the sedation protocol and the COMPORT scale. Compared with the control group, the intervention group showed significant decreases in the total usage of sedatives and analgesics, the duration of mechanical ventilation (11.0 days vs. 12.5 days) and PICU stay (15.0 days vs. 19.5 days), and the development of withdrawal symptoms (1 case vs. 7 cases). The total duration of sedation (8.0 days vs. 11.5 days) also tended to decrease. These findings suggest that application of protocol-based sedation with the COMPORT scale may benefit children requiring mechanical ventilation. PMID- 17728514 TI - Laparoscopic myomectomy for large myomas. AB - The aim of this study was to assess the feasibility and efficacy of laparoscopic myomectomy (LM) for large myomas. A subpopulation of 51 patients with myomas 8 cm or larger in diameter was selected from 155 patients who underwent LM at Kangbuk Samsung Hospital from July 2003 to November 2006. The mean age of the patients was 34.9 +/- 5.6 yr, mean parity was 0.6 +/- 0.9, and 8 patients had a previous operative history. The most common operative indication was a palpable abdominal mass (24 patients, 47%). The mean operating time was 85.6 +/- 38.9 min, and the mean diameter of the largest myoma was 9.3 +/- 1.8 cm. The mean change in hemoglobin concentration was 2.1 +/- 1.2 g/dL. Histopathological diagnosis included 49 patients of leiomyoma (96.1%) and 2 patients of leiomyoma with adenomyosis (3.9%). Postoperatively, a transfusion was done in 7 patients, and a case of subcutaneous emphysema was noted. None of the operations was switched to laparotomy. With the newly-developed screw and the port placement system that was modified from the Choi's 4-trocar method to obtain better surgical vision, LM of large myomas proved to be one of the efficient and feasible methods. PMID- 17728515 TI - Cervical length and the risk of microbial invasion of the amniotic cavity in women with preterm premature rupture of membranes. AB - The aims of this study were to determine whether sonographically measured cervical length is of value in the identification of microbial invasion of the amniotic cavity in women with preterm premature rupture of membranes (PPROM) and to compare its performance with maternal blood C-reactive protein (CRP), white blood cell count (WBC), and amniotic fluid (AF) WBC. This prospective observational study enrolled 50 singleton pregnancies with PPROM. Transvaginal ultrasound for measurement of cervical length was performed and maternal blood was collected for the determination of CRP and WBC at the time of amniocentesis. AF obtained by amniocentesis was cultured and WBC determined. The prevalence of a positive amniotic fluid culture was 26% (13/50). Patients with positive amniotic fluid cultures had a significantly shorter median cervical length and higher median CRP, WBC, and AF WBC than did those with negative cultures. Multiple logistic regression indicated that only cervical length had a significant relationship with the log odds of a positive AF culture. Transvaginal sonographic measurement of cervical length is valuable in the identification of microbial invasion of amniotic cavity in women with PPROM. Cervical length performs better than AF WBC, maternal blood CRP, and WBC in the identification of a positive amniotic fluid culture. PMID- 17728517 TI - Transvaginal ultrasonographic cervical measurement in predicting failed labor induction and cesarean delivery for failure to progress in nulliparous women. AB - The aim of this study was to evaluate the value of transvaginal sonographic cervical measurement in predicting failed labor induction and cesarean delivery for failure to progress in nulliparous women. One hundred and sixty-one women scheduled for labor induction underwent transvaginal ultrasonography and digital cervical examinations. Logistic regression demonstrated that cervical length and gestational age at induction, but not the Bishop score, significantly and independently predicted failed labor induction. According to the receiver operating characteristic curves analysis, the best cut-off value of cervical length for predicting failed labor induction was 28 mm, with a sensitivity of 62% and a specificity of 60%. In terms of the likelihood of a cesarean delivery for failure to progress as the outcome variable, logistic regression indicated that maternal height and birth weight, but not cervical length or Bishop score, were significantly and independently associated with an increased risk of cesarean delivery for failure to progress. Transvaginal sonographic measurements of cervical length thus independently predicted failed labor induction in nulliparous women. However, the relatively poor predictive performance of this test undermines its clinical usefulness as a predictor of failed labor induction. Moreover, cervical length appears to have a poor predictive value for the likelihood of a cesarean delivery for failure to progress. PMID- 17728516 TI - Changes in serum adenosine deaminase activity during normal pregnancy. AB - Adenosine deaminase (ADA), an enzyme essential for the differentiation of lymphoid cells, has been used for monitoring diseases with altered immunity. The purpose of this study was to investigate the changes in serum ADA activity throughout normal pregnancy. We measured the catalytic values of serum ADA from 202 normal pregnant women using a commercial kit. Subjects were divided into four groups according to the gestational age in weeks (Gwks) (Group I: 5-9 Gwks [n=58]; Group II: 15-20 Gwks [n= 63]; Group III: 24-30 Gwks [n=34]; Group IV: 30 39 Gwks [n=47]). The serum ADA levels for the Groups I, II, III, and IV were as follows: 20.1 +/- 6.9 IU/L, 20.0 +/- 7.6 IU/L, 37.9 +/- 19.9 IU/L, and 24.5 +/- 8.6 IU/L, respectively. The serum ADA activity of group III was significantly higher than the other groups (p<0.05). However, there was no significant correlation between the Gwks and the serum ADA activity. Furthermore, other parameters, such as maternal age (p=0.29), gestational age at delivery (p=0.07), delivery mode (p=0.39), and birth weight (p=0.59) had no correlation with ADA activity. Reference values of serum ADA in normal pregnancy may provide important database for making clinical decisions in pregnancies complicated by conditions where cellular immunity has been altered. PMID- 17728518 TI - Recurrent massive subcutaneous hemorrhage in neurofibromatosis type 1: a case report. AB - Neurofibromatosis type 1 (NF-1) is an autosomal dominant disorder that has three major features: multiple neural tumors, cafe-au-lait spots, and pigmented iris hamartomas (Lisch nodules). The purpose of this case report is to advise physicians of the danger associated with the progression of fast-onset massive hemorrhage to hemodynamic instability, which mandates rapid treatment to prevent the development of a life-threatening condition. A 64-yr-old woman with NF-1 was admitted to the Emergency Department (ED) because of a rapidly growing, 10 x 5 x 3 cm-sized mass on the left back area. She had previously undergone surgery for a large subcutaneous hematoma, which had developed on her right back area 30 yr before. She became hemodynamically unstable with hypotension during the next 3 hr after admission to ED. Resuscitation and blood transfusion were done, and the hematoma was surgically removed. The mass presented as a subcutaneous, massive hematoma with pathologic findings of neurofibroma. We report a case of NF-1 that presented as recurrent, massive, subcutaneous hemorrhage on the back region combined with hypovolemic shock. PMID- 17728519 TI - Traumatic tricuspid regurgitation following cardiac massage. AB - We report a 66-yr-old male patient who developed tricuspid regurgitation secondary to internal cardiac massage. After uneventful off-pump coronary artery bypass surgery, the subject experienced cardiac arrest in the intensive care unit. External cardiac massage was initiated and internal cardiac massage was performed eventually. A transesophageal echocardiography revealed avulsion of the anterior papillary muscle and chordae to the anterior leaflet after successful cardiopulmonary resuscitation. Emergency repair of the papillary muscle was performed under cardiopulmonary bypass. PMID- 17728521 TI - Clinico-pathological characteristics of congenital pulmonary lymphangiectasis: report of two cases. AB - Congenital pulmonary lymphangiectasis (CPL) is a rare, poorly documented disease, characterized by abnormal dilatation of pulmonary lymphatics without lymphatic proliferation. This disease is seen almost exclusively in infancy and early childhood. It can usually be divided into primary (congenital) and secondary forms. The primary form presents in neonates, and the patients mostly die due to the respiratory distress, shortly after birth. The authors experienced two cases of primary CPL in a 13-day-old male neonate and a one-day-old male neonate, showing prominent lymphatic dilatation in the septal, subpleural, and peri bronchial tissue throughout both lungs. The latter case was associated with congenital cardiac anomaly including single ventricle. These are unique cases of CPL in Korea of which the diagnosis was established through post-mortem examination. Therefore, the authors report these two cases with primary CPL with a review of the literature. PMID- 17728520 TI - Inflammatory myofibroblastic tumor on intercostal nerve presenting as paraneoplastic pemphigus with fatal pulmonary involvement. AB - Inflammatory myofibroblastic tumors (IMTs) are benign neoplasms that can occur at different anatomic sites with nonspecific clinical symptoms. A 48-yr-old woman presented with a 2-month history of a relapsed oral ulcer, progressive dyspnea, and a thoracic pain induced by breathing. A tumorous mass was noticed in the right costodiaphragmatic recess on chest computed tomography and magnetic resonance imaging, and the patient underwent a right costotransversectomy with excision of the tumor, which originated from the 12th intercostal nerve. Histology and immunohistochemistry showed that the tumor was an IMT of the intercostal nerve. The patient's postoperative course was not favorable; dyspnea persisted after surgery, and a progressive pulmonary compromise developed. The cause of the respiratory failure was found to be bronchiolitis obliterans, which in this case proved to be a fatal complication of paraneoplastic pemphigus associated with an IMT. This case of IMT of the spinal nerve in the paravertebral region is unique in terms of its location and presentation in combination with paraneoplastic pemphigus, which is rare. A brief review of the heterogeneous theories concerning the pathogenesis, clinicopathological features, and differential diagnosis of this disease entity is presented. PMID- 17728522 TI - Recurrent lower gastrointestinal bleeding from congenital arteriovenous malformation in the terminal ileum mimicking intestinal varicosis: a case report. AB - We report on an exceptional vascular cause of gastrointestinal hemorrhage. A 30 yr-old man was admitted because of recurrent hematochezia. Colonoscopy showed circumferential, erythematous, and nodular vascular distensions with hematocystic spots in the terminal ileum resembling varicosis and subsequent computed tomography with 3-dimensional angiographic reconstruction revealed a vascular architecture around the terminal ileum. No other potential source of bleeding was identified. The patient was treated by ileocecectomy and the final diagnosis was of an arteriovenous malformation confined to the terminal ileum. He has been followed up without a further hemorrhagic episode. PMID- 17728523 TI - Combined hepatic and splenic abscesses in a patient with ulcerative colitis. AB - Liver abscesses are very rare complications of ulcerative colitis, and furthermore, there has been only one case of splenic abscess in a patient with ulcerative colitis reported in the English literature. We recently encountered a patient with ulcerative colitis accompanied by both hepatic and splenic abscesses. The patient was treated with abscess drainage as well as sulfasalazine and antibiotics. Follow-up sonography of the abdomen showed complete resolution of the lesions. To our knowledge, this is the first report of combined case of multiple liver abscesses combined with splenic abscess in a patient with ulcerative colitis. PMID- 17728524 TI - Solitary extramedullary plasmacytoma of the liver without systemic monoclonal gammopathy. AB - Extramedullary plasmacytoma of the liver is a very rare tumor. Although a few cases of extramedullary plasmacytoma of the liver have been reported, we could not find any report on truly localized extramedullary plasmacytoma of the liver in the literature. The patient was a 63-yr-old man who exhibited a solitary liver mass on dynamic computed tomography and magnetic resonance imaging. Histologically, the tumor was composed of mature plasma cells with mild atypia. Immunohistochemistry demonstrated monoclonal IgG and Kappa light chain expression. Bone marrow examination revealed no abnormalities. There was no evidence of a monoclonal protein in the serum and urine, lytic bone lesions, anemia, renal insufficiency, and hypercalcemia. The patient was treated with 5,000 cGy of radiotherapy, and the tumor disappeared 6 months after treatment. PMID- 17728525 TI - A case of deep vein thrombosis and pulmonary thromboembolism after intravenous immunoglobulin therapy. AB - Although high-dose intravenous immunoglobulin (IVIG) is generally considered a safe medication for various immune-mediated diseases, thrombotic events have been reported as a complication of the therapy. We report a case who developed thrombotic complications after receiving IVIG. A 56-yr-old woman with idiopathic thrombocytopenic purpura received IVIG at a dose of 400 mg/kg/day for five days. Three days after the administration of IVIG, the patient developed painful edema in the left leg. Lower extremity doppler ultrasound revealed deep vein thrombosis in the left leg. Chest computed tomography (CT) scan demonstrated a filling defect indicating thromboembolism of the right pulmonary artery. After three weeks of enoxaparin therapy, her symptoms and pulmonary embolism on CT improved. This case suggests clinicians should be cautious in the development of thromboembolism by administration of IVIG, especially in patients with thrombophilia. PMID- 17728526 TI - Syringocystadenocarcinoma papilliferum: a case report. AB - Syringocystadenocarcinoma papilliferum (SCACP) is a rare form of adenocarcinoma of the skin. This is the malignant counterpart of syringocystadenoma papilliferum (SCAP) and usually develops on the scalp in a long-standing lesion identified clinically as SCAP. We describe a 65-yr-old Korean man with a nodule on the right supra-pubic area with a 2-yr duration. Histologically this tumor had a similar overall configuration as in SCAP, but the tumor was asymmetric and poorly circumscribed, extending into the deep dermis and showed cytologic atypia. The tumor cells showed positive reaction to GCDFP-15, but negative reaction to CEA and HMFG-1. We established the diagnosis of SCACP in the patient, and a wide excision was performed to remove the tumor. The patient has been well without relapse or metastasis for 2 yr. PMID- 17728527 TI - Hysteroscopic resection of the vaginal septum in uterus didelphys with obstructed hemivagina: a case report. AB - Uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis is a rare congenital anomaly. Excision of the obstructed vaginal septum is the treatment of choice for symptom relief and the preservation of reproductive capability. A 14-yr-old girl complained of persistent vaginal spotting following each menstruation. Pelvic magnetic resonance imaging revealed a uterus didelphys with left hematocolpos and ipsilateral renal agenesis. Instead of conventional transvaginal excision of the vaginal septum, we used hysteroscopic excision under transabdominal ultrasonographic guidance to preserve the integrity of the hymen. The postoperative course was uneventful, and clinical symptoms were completely resolved after this intervention. Resectoscopic excision of the vaginal septum was found to be easy, safe, effective, and appropriate for young women as it preserved hymen integrity. We believe that this is the first Korean report on the use of a hysteroscopy for vaginal septum resection in a patient with uterus didelphys with obstructed hemivagina. PMID- 17728528 TI - Community-acquired versus nosocomial Klebsiella pneumonia bacteremia: clinical features, treatment outcomes, and clinical implication of antimicrobial resistance. PMID- 17728529 TI - Self-reported snoring, maternal obesity and neck circumference as risk factors for pregnancy-induced hypertension and preeclampsia. AB - BACKGROUND: Physical and hormonal changes during pregnancy alter breathing patterns of pregnant women. It is possible that occult disordered breathing during sleep may be a risk factor for the development of pregnancy-induced hypertension (PIH) and preeclampsia. OBJECTIVE: Our aim was to determine the incidence of self-reported snoring in pregnant women, and to investigate the relationship of snoring, obesity and neck circumference to PIH and preeclampsia. METHODS: 469 pregnant women and 208 age-matched nonpregnant women were included in the study. Both groups were asked to complete a questionnaire. Maternal complications were retrieved from the medical records. RESULTS: Habitual snoring was reported from 1.9% of nonpregnant women, 2.5% of pregnant women prior to pregnancy and 11.9% of those same women during the third trimester of pregnancy (p < 0.001). Age, smoking during pregnancy, and weight before delivery were independent risk factors for habitual snoring in pregnancy. PIH and preeclampsia developed in 20 and 10.9% of pregnant women with habitual snoring, as compared to 11 and 5.8% of non-snoring pregnant women (p = 0.045, p = 0.125, p = 0.415), respectively. In women who developed preeclampsia, weight before pregnancy, weight before delivery and neck circumference were significantly higher in univariate analysis. Neck circumference was an independent risk factor for PIH and preeclampsia according to logistic regression analysis. CONCLUSION: The incidence of snoring is significantly higher in pregnant women than in nonpregnant women. Snoring may indicate a risk of PIH. Neck circumference was an independent risk factor for both PIH and preeclampsia. PMID- 17728530 TI - Bariatric surgery in the treatment of obstructive sleep apnea in morbidly obese patients. AB - BACKGROUND: Weight loss has been shown effective in the treatment of the obstructive sleep apnea-hypopnea syndrome. Regrettably, many obese patients are unable to achieve sustained and useful weight loss by dietary means. Recently, bariatric surgery has emerged as an alternative to treat obesity and many of its comorbidities, although its role for sleep apnea treatment is still not defined. OBJECTIVES: To evaluate the impact of bariatric surgery on obstructive sleep apnea in morbidly obese patients. METHODS: In this cohort study, polysomnography, Epworth Sleepiness Scale questionnaire and clinical assessment were performed in 12 of 13 morbidly obese patients with moderate to severe obstructive sleep apnea treated with bariatric surgery through Roux-en-Y gastric bypass procedure after a minimum of 18 months post surgery. RESULTS: The mean (+/-SD) loss of excess body weight was 70.5 +/- 24%. The mean level obtained in the Epworth Scale was 4.8. There was a significant reduction in the apnea-hypopnea index, from a median of 46.5 (range: 33-140) to 16 (range: 0.9-87) events per hour (p < 0.05), an improvement in mean oxygen saturation from 85.7 +/- 5.1 to 94.5 +/- 3.6% (p < 0.05) and in minimum oxygen saturation from 64.7 +/- 13.4 to 78.7 +/- 13.7% (p < 0.05). The magnitude of the weight loss and the improvements in mean and minimum oxygen saturation were positively correlated, (r = 0.76; p or=15% below baseline within 30 min of dosing), cough episodes and adverse events. RESULTS: Thirty-two patients were included in the per-protocol population (mean age 27 years, 62.5% males). The mean percentage decrease in FEV(1) was comparable between treatment groups: -1.6% (Respimat SMI pH 2.7), -1.8% (Respimat SMI pH 7.0), -1.9% (CFC-MDI), and -2.3% (Respimat SMI pH 3.4); no patient experienced paradoxical bronchoconstriction. The mean number of cough episodes was significantly lower in the Respimat SMI pH 2.7 group versus CFC-MDI (p = 0.0165). No patient used rescue medication. Only 3 patients experienced at least one adverse event. CONCLUSIONS: The Respimat SMI pH 2.7 placebo solution does not induce adverse events in these patients. Compared with the CFC-MDI placebo suspension, Respimat SMI is a well-tolerated inhaled medication delivery system that can accommodate medication formulations with a wide range of pH solutions. PMID- 17728531 TI - Incidence rate and factors related to post-bronchoalveolar lavage fever in children. AB - BACKGROUND: Post-bronchoscopy and bronchoalveolar lavage (BAL) fever in children has been described by several authors. OBJECTIVES: This study aimed at assessing the occurrence of fever after these examinations and associated risk factors. METHODS: The study was performed in the Bronchoscopy Unit of Hopital Necker Enfants Malades, Paris, France, from June 2004 to July 2005. 148 children who underwent fiberoptic bronchoscopy and BAL, and remained in the Unit for 24 h, were included. RESULTS: 37.8% of the patients presented post-BAL fever. In the multivariate analysis of the selected factors (age, immunodeficiency, general or local anesthesia, mucosal biopsy, inflammation and suppuration at the moment of the examination, abnormal bronchoalveolar fluid cellularity and infection), only age <2 years and presence of infection remained associated with fever. CONCLUSIONS: The occurrence of fever is a frequent event in children who underwent BAL. In order to reduce post-BAL fever, antibiotic strategies should be devised based on prospective studies assessing identification of predictive air way infection criteria and/or rapid bacteriological result analysis. PMID- 17728533 TI - Symptomless aspiration of a dental drill. PMID- 17728534 TI - Pleural fluid PCR method for detection of Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae in pediatric parapneumonic effusions. AB - BACKGROUND: Parapneumonic effusions cause significant morbidity and mortality despite current developments in diagnostic and therapeutic approaches. Causative microorganisms may remain unidentified in a significant number of patients by cultures and Gram smears. Polymerase chain reaction (PCR) is a molecular technique for the detection of causative bacteria; however, its efficiency in pleural fluids is less known. OBJECTIVES: The present study was performed to compare the efficiency of PCR in the detection of the three most common organisms (Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae) with conventional methods. METHODS: Twenty-eight consecutive patients with parapneumonic pleural effusions were studied. On admission, pleural fluid samples were obtained for Gram staining, routine culture and PCR analysis for S. aureus, S. pneumoniae and H. influenzae. RESULTS: PCR analysis allowed detection of 11 microorganisms in 10 patients (35.7%), whereas pleural fluid cultures detected the etiological agent in only 2 (7.1%). S. pneumoniae was the most frequent agent. CONCLUSIONS: Pleural fluid cultures may have low diagnostic yields, partly due to prior antibiotic use. Pleural fluid PCR analysis may improve the etiologic diagnosis in parapneumonic pleural effusions, with technical advances leading to higher yields than obtained in this study. PMID- 17728535 TI - 17-Beta-estradiol directly regulates the expression of adrenergic receptors and kisspeptin/GPR54 system in GT1-7 GnRH neurons. AB - Estradiol plays a critical role in the feedback regulation of reproduction, in part by modulating the neurosecretory activity of gonadotropin-releasing hormone (GnRH) neurons. While indirect effects of estradiol on GnRH neurons have been clearly demonstrated, direct actions are still controversial. In the current study, we examined direct effects of 17beta-estradiol upon the expression of receptors for afferent signals at the level of the GnRH neuron, using immortalized GT1-7 cells. Using RT-PCR, we confirmed the expression of mRNA for the adrenergic receptors (AR) alpha(1)A-, alpha(1)B-, alpha(1)D-, alpha(2)A-, alpha(2)C-, and beta(1)-AR, and showed for the first time that mRNAs for alpha(2)B-, beta(2)- and beta(3)-AR, for kisspeptin and its receptor GPR54 and for the novel estrogenic receptor GPR30 are expressed in GT1-7 cells. After treatment with 10 nM 17beta-estradiol, alpha(1)B-AR mRNA was significantly increased (14-fold) after 6 h as determined by real-time PCR, while alpha(1)B- and alpha(1)D-AR mRNA were significantly increased (19- and 23-fold, respectively) after 24 h. The expression of KiSS-1 and GPR54 mRNAs were also significantly increased (8- and 6-fold, respectively) after 24 h treatment of GT1 7 cells with estradiol. GPR30 mRNA expression was not affected by estradiol. Our data also showed that kisspeptin-10 (1-10 nM) can significantly stimulate GnRH release and GnRH mRNA expression in GT1-7 cells. These results suggest that the complex physiologic effects of estradiol on the function of the reproductive axis could be mediated partly through direct modulation of the expression of receptors for afferent signals in GnRH neurons. PMID- 17728536 TI - Lack of association of -55CT polymorphism of UCP3 gene with fat distribution in obese patients. AB - BACKGROUND AND AIMS: Some studies have pointed to a role of UCP3 in the regulation of whole-body energy homeostasis and regulation of fat distribution. The aim of our study was to investigate the influence of -55CT polymorphism of UCP3 gene on fat distribution and classical cardiovascular risk factors in obese patients. DESIGN: A population of 225 obese patients was analyzed in a prospective way. A nutritional evaluation was performed. Dietary intake and exercise were recorded. The genotype of UCP3 gene -55CT was studied. RESULTS: 225 patients gave informed consent and were enrolled. 178 (53 males/125 females) (79.1%) had genotype 55CC (wild group) and 47 patients (14 males/33 females) (20.9%) 55CT (mutant group). In the mutant group, resting metabolic rate was higher than in the wild group. However, resting metabolic rate corrected by fat free mass was similar. No differences were detected in fat mass or other anthropometric parameters. C-reactive protein was higher in the mutant group than in the wild group (5.1 +/- 5.7 vs. 6.9 +/- 6.8 mg/dl; p < 0.05). CONCLUSION: In the mutant group of -55CC UCP3 gene patients, C-reactive protein was higher than in the wild-type patients. However, no differences in anthropometric parameters were detected in either group. PMID- 17728537 TI - Taurine induces anti-anxiety by activating strychnine-sensitive glycine receptor in vivo. AB - Taurine has a variety of actions in the body such as cardiotonic, host-defensive, radioprotective and glucose-regulatory effects. However, its action in the central nervous system remains to be characterized. In the present study, we tested to see whether taurine exerts anti-anxiety effects and to explore its mechanism of anti-anxiety activity in vivo. The staircase test and elevated plus maze test were performed to test the anti-anxiety action of taurine. Convulsions induced by strychnine, picrotoxin, yohimbine and isoniazid were tested to explore the mechanism of anti-anxiety activity of taurine. The Rotarod test was performed to test muscle relaxant activity and the passive avoidance test was carried out to test memory activity in response to taurine. Taurine (200 mg/kg, p.o.) significantly reduced rearing numbers in the staircase test while it increased the time spent in the open arms as well as the number of entries to the open arms in the elevated plus maze test, suggesting that it has a significant anti-anxiety activity. Taurine's action could be due to its binding to and activating of strychnine-sensitive glycine receptor in vivo as it inhibited convulsion caused by strychnine; however, it has little effect on picrotoxin-induced convulsion, suggesting its anti-anxiety activity may not be linked to GABA receptor. It did not alter memory function and muscle activity. Taken together, these results suggest that taurine could be beneficial for the control of anxiety in the clinical situations. PMID- 17728538 TI - Cancer 'chemotherapia specifica' ninety years after Paul Ehrlich. AB - From his student days throughout his whole life, Paul Ehrlich tried hard to obtain 'chemotherapia specifica' for the harmless systemic therapy of infectious diseases. Given the poor therapeutic benefit obtained with cytotoxic therapeutic agents and empirical radiopharmaceuticals, so far used only for neoadjuvant and adjuvant treatments of cancer, we have tried to develop Paul Ehrlich's 'chemotherapia specifica' for safe and effective therapy of cancers in cigarette smokers. With the help of sector-field inductively coupled plasma mass spectrometry, we have tried to find the metabolic action of cigarette smoke constituents in the cancerous organ. On the basis of these results we are synthesizing pharmaceuticals and radiopharmaceuticals to purge the tobacco constituent metabolic products that cause cancer. The purity, stability and chemical nature of the pharmaceuticals and radiopharmaceuticals required for therapy have been studied by chromatography and electrophoresis. The cancer specificity of the therapeutic agent has been examined by the total body distribution of its gamma- and beta-labelled species in solution. At present, a bladder cancer-specific therapeutic agent is being developed. PMID- 17728539 TI - Observational study of hepatic cytochrome P-450 protein expression and activity in summer flounder (Paralichtys dentatus) after combination ormetoprim sulfadimethoxine treatment. AB - The metabolism of aquaculture antibiotics on the piscine, hepatic cytochrome P 450 (CYP) system has not yet been defined. Fifty summer flounder, maintained at 20 degrees C, were fed ormetoprim-sulfadimethoxine (Romet-30(R)) at 1% body weight daily and were randomly sampled before treatment and on days 1, 6, 10 and 21 after treatment. Western blotting of hepatic microsomes included goat antirat CYP1A1 and rabbit antihuman CYP3A4 serum. Catalytic activities comprised: 3-cyano 7-ethoxycoumarin (CEC), 7-benzyloxy-4-trifluoromethylcoumarin (BFC), resorufin benzyl ether (BzRes). Treatment induced CYP1A1 and CYP3A4 expression. Dealkylation of CEC (CYP1A2) was increased after treatment. Romet-30 inhibited CYP3A4 activity measured by BFC, but induced BzRes CYP3A4. The usefulness of mammalian antibodies for piscine P-450 Western blotting was demonstrated. The hepatic P-450 1A2 and 3A4 metabolism was quantifiable by kits developed for mammalian microsomes. PMID- 17728541 TI - Endovascular treatment of aortic aneurysms: techniques and clinical update. AB - Open repair of abdominal and thoracic aortic aneurysms continues to be associated with considerable morbidity and mortality. Endovascular repair of abdominal and thoracic aortic aneurysms has evolved over the past few years and has significantly reduced the morbidity of aortic aneurysm repair compared with the standard open surgical procedures. Several devices have been approved for clinical use for this purpose. This has allowed the treatment of patients who are otherwise at high risk for open repair. This review paper aims to (1) describe the general principles of use for endovascular devices and review the radiographic features and clinical trials for the devices in current use, (2) present the results of the clinical trials that led to the approval and marketing of the current devices, and (3) review new techniques and approaches for the treatment of aortic aneurysms. PMID- 17728540 TI - Influence of subinhibitory concentrations of protein-synthesis-inhibiting antibiotics on production and release of the pneumococcal virulence factor pneumolysin in vitro. AB - OBJECTIVE: Pneumolysin is an important virulence factor of Streptococcus pneumoniae with cytotoxic and proinflammatory activities released during growth and autolysis. At concentrations above the minimal inhibitory concentration, the protein-synthesis-inhibiting antibiotics erythromycin, clindamycin and rifampicin inhibit the production and/or release of virulence factors in various bacterial species. We investigated the influence of subinhibitory concentrations of these antibiotics on production and release of pneumolysin by S. pneumoniae strain D39. METHODS: The pneumococcal strain D39 was grown in broth and treated with antibiotics at a concentration of 1/32 of the respective minimal inhibitory concentration. Cytoplasmic and extracellular pneumolysin was measured by quantitative immunoblotting with recombinant pneumolysin as standard. RESULTS: The subinhibitory antibiotic concentrations evaluated did not affect bacterial growth. During logarithmic growth, production of pneumolysin was decreased by clindamycin, erythromycin and rifampicin by approximately 50% compared with untreated controls. The release of pneumolysin was decreased to a similar extent. CONCLUSION: A decrease in pneumolysin production by 50% probably has a moderate biological effect. We do not advocate the use of subinhibitory concentrations of antibiotics to modulate the expression of virulence factors during pneumococcal disease, particularly with regard to the risk of development of antibiotic resistance. PMID- 17728542 TI - Statin therapy: changing the mode of coronary heart disease. PMID- 17728543 TI - Methamphetamine-associated acute left ventricular dysfunction: a variant of stress-induced cardiomyopathy. AB - This brief report describes a case of transient left ventricular dysfunction in a 42-year-old woman associated with methamphetamine abuse. Transient (stress induced) left ventricular dysfunction has been described previously, usually in postmenopausal women following emotional stress and also severe medical illness. This is the first reported case associated with methamphetamine abuse. PMID- 17728544 TI - In vivo visualization of early microcirculatory changes following ischemia/reperfusion injury in human kidney transplantation. AB - To determine whether microcirculatory changes following ischemia/reperfusion (I/R) may serve as predictors for subsequent graft dysfunction, we used noninvasive orthogonal polarization spectral (OPS) imaging to directly visualize and quantify cortical kidney microcirculation. In a total of 13 combined kidney/pancreas recipients, following reperfusion (5/30 min) microcirculatory parameters such as capillary diameter, functional capillary density (FCD) and red blood-cell velocity (V(RBC)) of the renal graft were analyzed. From these parameters, a heterogeneity index (HI) and volumetric capillary blood flow (vCBF) were calculated. In addition, the extent of graft injury was determined by daily analysis of serum creatinine, blood urea nitrogen, C-reactive protein and systemic leukocyte count for 7 days post-transplant. At early reperfusion, a heterogeneous perfusion pattern with oscillating flow and scattered microvascular thrombosis of peritubular capillaries, resembling a 'no reflow', was observed. FCD was constant throughout the entire reperfusion period, whereas HI, capillary diameters, V(RBC) and vCBF increased. The latter showed a significant positive correlation with creatinine changes between days 1 and 3. So far our finding of a positive correlation of early microvascular changes (vCBF) and clinical parameters (creatinine) indicate a possible therapeutic implication of OPS imaging to predict early I/R-induced renal graft dysfunction. PMID- 17728545 TI - Lumbar intradural extramedullary bronchiogenic cyst. AB - The pathological findings of an intradural and extramedullary cyst at the L1 level of the spinal canal are described in a 28-year-old male who presented with chronic lumbago and progressive weakness and numbness in both lower limbs. Histopathological examination revealed the diagnosis of bronchiogenic cyst. Bronchiogenic cysts in the spinal canal are uncommon, and cysts at the L1 level are extremely rare. Their pathogenesis is still poorly understood. They are thought to be a malformation arising from a split notochordal syndrome. We conclude that intradural extramedullary bronchiogenic cysts may appear also at lumbar levels. Surgical resection can be achieved with good outcome. PMID- 17728546 TI - HPV-2 isolates from patients with huge verrucae vulgaris possess stronger promoter activities. AB - OBJECTIVES: To assess the influences of the mutations within the long control region (LCR) and E2 open reading frame (ORF) of the human papillomavirus-2 (HPV 2) isolates from patients with extensive verrucae vulgaris with cutaneous horns in the activities of the viral early promoters. METHODS: A PCR method was applied for screening HPV DNA in the lesion specimens and the complete HPV-2 genomes was analyzed. Recombinant CAT-reporter plasmids containing various HPV-2 LCRs and mammalian expression plasmids containing E2 ORF were constructed. The promoter activity was evaluated by transient transfection. RESULTS: The whole HPV-2 genomes were obtained from both patients. Several mutations in LCR and mutations leading to alterations of amino acids in E2 protein were identified in isolate-1, while a few point mutations in LCR were seen in isolate-2. Under the control of LCRs, the viral early promoter activities of isolate-1 and isolate-2 were increased 3- and 2-fold, respectively. Alterations of amino acids in E2 protein of isolate-1 partially abolished its promoter repressive activity. Compared with that of prototype HPV-2, the promoter activity of isolate-1 in the presence of its E2-expressing plasmid was significantly increased. CONCLUSIONS: The increased promoter activities might be linked, at least partially, to the clinical phenotypes of the uncommon huge verrucae vulgaris. PMID- 17728547 TI - Prediction of response to pegylated interferon and ribavirin in hepatitis C by polymorphisms in the viral core protein and very early dynamics of viremia. AB - OBJECTIVE: To evaluate power of amino acid polymorphisms in core protein of hepatitis C virus (HCV) for predicting sustained virological response (SVR) to pegylated interferon (Peg-IFN)/ribavirin, when they were combined with virological response. METHODS: Peg-IFN/ribavirin was given to 118 patients infected with HCV genotype 1b in high viral loads. Amino acid polymorphisms (Arg70 vs. Gln70 and Leu91 vs. Met91) in combination with on-treatment virological responses were correlated with SVR. RESULTS: End-of-treatment response (ETR) was achieved in 71% and SVR in 47% of the 118 patients. In multivariate analysis, Arg70 and Leu91, and higher ribavirin dose were independently associated with ETR. In patients with Gln70 and/or Met91, SVR was more frequent in those with than without prompt virological response (PVR) for a decrease in viral load >or=1.0 log by 48 h. Specificity in predicting patients without ETR and SVR, in combination with core polymorphisms, was not different between PVR and early virological response at 12 weeks. CONCLUSION: Core polymorphisms combined with PVR would be useful in promptly identifying the patients who will not respond to Peg-IFN/ribavirin, thereby avoiding unrewarding side effects and high costs. PMID- 17728549 TI - Ocular photodynamic therapy--standard applications and new indications. Part 2. Review of the literature and personal experience. AB - Photodynamic therapy (PDT) has become a well-established treatment for vascular forms of age-related macular degeneration (AMD). The implementation of evidence based medicine principles into the treatment regimen of AMD seems to be immensly important, since AMD continues to be the most frequent cause of blindness among patients older than 65 years in industrialized countries. Numerous randomized prospective studies demonstrated high levels of evidence for the efficacy of various treatment approaches such as laser photocoagulation, PDT, subretinal surgery or novel anti-angiogenic drugs [Arch Ophthalmol 2006;124:597-599]. The high evidence shown by these studies supported the rationale to use PDT also in additional, less frequent, vasoproliferative diseases. Although these 'case series' and 'individual case control studies' have a low level of evidence, they give us important information for treatment decisions in these rare conditions. The goal of this survey is to review the current literature regarding PDT in vasoproliferative and exudative ocular diseases outside AMD. Many studies modified the treatment parameters of PDT to address the specific pathology of the underlying disease. Table 1 summarizes the diseases and treatment parameters that are described in this part 2, the entire table of this review is included in part 1 (www.karger.com/doi/10.1159/ 000101922). PMID- 17728550 TI - Assessment of central serous chorioretinopathy by optical coherence tomography and multifocal electroretinography. AB - PURPOSE: To evaluate central serous chorioretinopathy (CSCR) by means of optical coherence tomography (OCT) and multifocal electroretinogram (mf-ERG) at presentation and after resolution of the acute phase. DESIGN: Prospective comparative observational case series with a normal sample. PATIENTS AND METHOD: Twenty-one eyes of 21 patients with unilateral CSCR were examined. Both eyes underwent complete ophthalmological examination, which included measurement of best-corrected visual acuity, fluorescein angiography, OCT and mf-ERG recording. Our results were compared with the corresponding findings of 33 normal volunteers of the same age. RESULTS: At presentation, the averaged mean retinal thickness of the fovea, measured by OCT, was 303 mum in the affected eyes, 69.3% higher compared to the normal controls (p < 0.001). The averaged mean retinal response density of the mf-ERG of the affected eyes in area 1 was 11.29 nV/degree(2), 50.8% lower compared to the normal controls (p < 0.001). After regression of CSCR, the averaged mean retinal thickness of the fovea was 213 microm in the affected eyes, 19.3% greater compared to the normal controls (p < 0.001). The averaged mean retinal response density of the mf-ERG of the affected eyes in area 1 was 16.05 nV/degree(2), 30.1% lower compared to normal controls (p < 0.001). It is interesting that 6 of 21 fellow nonaffected eyes showed abnormal values, with an averaged mean retinal thickness of OCT (246 mum) and an averaged mean retinal response density of mf-ERG in area 1 (12 microV/degree(2)). In the remaining 15 eyes, the OCT and the mf-ERG values were within normal limits. PMID- 17728551 TI - Analysis of retinal nerve fiber layer thickness in patients with pseudoexfoliation syndrome using optical coherence tomography. AB - OBJECTIVE: To evaluate the retinal nerve fiber layer (RNFL) thickness in patients with unilateral pseudoexfoliation syndrome (PXS) without glaucoma by using optical coherence tomography (OCT). METHODS: 22 patients with unilateral PXS were evaluated. Group 1 included the eyes with the pseudoexfoliation, group 2 included the fellow eyes; 18 age-matched normal control eyes were assessed in group 3. The mean and segmental RNFL thickness in eyes with pseudoexfoliation and their fellow eyes in patients with unilateral PXS was compared to age-matched control subject eyes. RESULTS: The RNFL in patients with PXS were significantly thinner than controls in all quadrants except the nasal quadrant with regard to segmental analysis (p < 0.05). This RNFL loss was apparent at 7, 10 and 11 o'clock of the PXS eyes with regard to clock hour position (p < 0.05). In the fellow eyes, no significant difference in RNFL measurement was found except the temporal quadrant when compared with the controls. In the analysis with regard to clock hour position, no significant reduction in RNFL thickness was found except in the 11 o'clock segment. In PXS eyes, RNFL thicknesses at the inferior quadrant and the 1 , 2- and 5-o'clock segments were significantly lower than in non-PXS eyes (p < 0.05). CONCLUSIONS: This study suggests that PXS without glaucoma may be associated with a thinner RNFL compared with those of age-matched control subjects and non-PXS fellow eyes. Further studies are needed to clarify the relationship between the decrease in RNFL thickness and the development of glaucomatous damage in eyes with pseudoexfoliation. PMID- 17728552 TI - The use of ultrasound biomicroscopy in the evaluation of anterior segment tumors and simulating conditions. AB - PURPOSE: To report the ultrasound biomicroscopy (UBM) findings of anterior segment tumors and simulating conditions. METHODS: Thirty-five patients underwent UBM. Of those, 16 had histopathologically or cytopathologically diagnosed tumors, and 19 had clinically diagnosed lesions. RESULTS: The study material comprised 13 iris pigment epithelial (IPE) cysts, 7 ciliary body melanomas, 4 iris melanomas, 4 iris nevi, 3 intraocular invasions of conjunctival squamous cell carcinoma, 2 ring melanomas of the anterior chamber angle, 1 medulloepithelioma and 1 pars plana cyst. On UBM, all IPE cysts presented as cystic lesions with a thin cyst wall and no solid components. All ciliary body melanomas showed low to medium reflectivity, with cavitation in one case and extraocular extension in another. Iris melanomas presented as anterior (stromal) iris lesions with medium to high internal reflectivity. There was irregularity and convex bowing of the posterior iris plane in iris melanomas, a feature not seen in iris nevi. Intraocular invasion of conjunctival squamous cell carcinoma was evidenced as areas of medium to high reflectivity in the ciliary body and iris, loss of the acute angle shape and highly reflective spots in the anterior chamber. CONCLUSIONS: UBM was particularly useful in the diagnosis of IPE cysts, in the visualization of small ciliary body melanomas, in the differentiation of iris melanomas from iris nevi and in the demonstration of intraocular invasion from conjunctival squamous cell carcinoma. PMID- 17728553 TI - Efficacy of photodynamic therapy in the management of occult choroidal neovascularization associated with serous pigment epithelium detachment. AB - AIMS: To evaluate the efficacy of photodynamic therapy (PDT) in the treatment of subfoveal occult choroidal neovascularization (CNV) associated with serous pigment epithelium detachment (PED) in eyes with age-related macular degeneration. METHODS: Hundred and fifty-three patients (161 eyes) with subfoveal occult CNV due to age-related macular degeneration, were divided into two groups. The first group (70 patients, 75 eyes) included eyes with occult CNV associated with serous PED of at least 1 disc diameter in size and the second (83 patients, 86 eyes) eyes with late leakage of undetermined source. All the patients were treated with PDT. The follow-up time ranged from 12 to 48 months. RESULTS: At the last examination, in the first group, the visual acuity (VA) improved or remained stable in 17 (22.7%) and decreased in 58 (77.3%). In the second group, the VA improved or remained stable in 37 (43%) and decreased in 49 (57%). The difference in the change (decrease) in the VA between the two groups was statistically very significant (p = 0.0075). Retinal pigment epithelium tear occurred in 15 eyes (20%) of the first group. CONCLUSION: Our study showed that the visual prognosis of eyes treated with PDT due to subfoveal occult CNV associated with serous PED is not favorable. We believe that the distinction between the two forms of occult CNV is essential, as they carry a different prognosis. PMID- 17728554 TI - Systemic adverse events: a comparison between topical and peribulbar anaesthesia in cataract surgery. AB - AIMS: To evaluate the safety of topical anaesthesia (TA) versus peribulbar anaesthesia (PBA) in patients undergoing routine cataract surgery on the basis of systemic adverse events. METHODS: In this retrospective study, a total of 2,020 consecutive cases of cataract surgery performed by one surgeon on 1,621 patients with PBA (n = 1,010; between 1998-1999) or TA (n = 1,010; between 1999-2001) were evaluated on the basis of intra-operative and early postoperative adverse events requiring medical intervention. RESULTS: The rate of pre-existing risk factors in patients undergoing cataract surgery is high (97%). Complications are significantly less frequent in TA than in PBA in the intra-operative (p < 0.001) and postoperative (p = 0.022) courses. The incidence of intra-operative complications is higher in elderly patients (>or=65 years of age) than in younger patients (p < 0.001). CONCLUSION: The results from the present study indicate that intra-operative complications are less likely in patients that receive TA, suggesting the use of TA for routine cataract surgery both in young patients and particularly in elderly patients when there are no contraindications in the individual case. PMID- 17728555 TI - Antiadenoviral effect of the alpha 5 beta 1 integrin receptor ligand, GRGDSP peptide, in serotypes that cause acute keratoconjunctivitis. AB - BACKGROUND/AIMS: In adenoviral conjunctivitis, the infection process starts by the attachment of adenoviral fibers to conjunctival epithelial cells that contain the receptor for the adenovirus. The alpha 5 beta 1 integrin receptor ligand, GRGDSP peptide, contains the arginine-glycine-aspartate-binding motif which is common to the Coxsackie adenovirus receptor and integrins that are known to be adenoviral receptors. We evaluated the antiadenoviral effect of an expected adenoviral receptor inhibitor, GRGDSP peptide,in vitro. METHODS: Adenovirus types 3, 4, 8, 19 and 37 were used. After calculating the 50% cytotoxic concentration of GRGDSP peptide, the adenovirus was cultivated with the agent for 7 days under serial dilution. Adenoviral DNA was qualitatively measured by real-time PCR. RESULTS: GRGDSP peptide showed an inhibitory effect against adenoviral proliferation in all serotypes except type 4 in a dose-dependent manner. CONCLUSION: This result suggests that the alpha 5 beta 1 integrin receptor ligand, GRGDSP peptide, has antiadenoviral activity in vitro, and the possibility of being used for local treatment of epidemic keratoconjunctivitis. PMID- 17728556 TI - Clinicopathological analysis of periocular sebaceous gland carcinoma. AB - BACKGROUND: We analyzed the clinicopathological features and prognosis in patients with periocular sebaceous gland carcinoma. METHODS: Retrospectively, we studied the records of 24 cases of sebaceous gland carcinoma treated in our clinic between 1999 and 2004. The reviewed data included demographic information, initial clinical and histopathological diagnosis, anatomic tumor location, details of treatment, tumor involvement of resection margin, and outcomes such as local recurrence, distant metastasis and survival. RESULTS: Local recurrence developed in 6 cases (25%) at a median of 20 months from initial diagnosis. Only 2 patients (8.3%) died of systemic metastasis to brain and bone from primary lacrimal gland carcinoma. The local recurrence rate in the complete excision group (5.9%) was significantly lower compared with the incomplete excision with irradiation group (71.4%; Fisher's exact test, p = 0.003). We observed a shorter duration of symptom, a higher rate of eventual exenteration and local recurrence, and a shorter time interval to local recurrence from initial management in poorly differentiated tumors compared with moderately differentiated tumors. CONCLUSION: It is critical to achieve a negative tumor margin in both frozen and permanent section to prevent local recurrence. Early aggressive management is required in sebaceous gland carcinoma of the lacrimal gland, as its mortality is much higher than that of eyelid origin. PMID- 17728557 TI - Medical costs of glaucoma and ocular hypertension in Italian referral centres: a prospective study. AB - AIM: This study analyzes the resource utilization and costs of ocular hypertension and glaucoma (staged by severity) in Italian ophthalmology departments. METHODS: The project was a multi-centre observational study conducted in 17 Italian ophthalmology departments throughout the country. A total of 659 patients were recruited and followed prospectively for 1 year. For the purpose of analysis, the patients were divided into 3 groups according to the severity at onset: ocular hypertension, glaucoma and advanced glaucoma. RESULTS: The subgroups differed significantly in the main demographic and clinical variables. As expected, greater severity was associated with older mean age and worse visual acuity, and with higher resource consumption and costs. The annual average cost per patient was EUR 788.7 and rose significantly with disease severity (EUR 572.0 for ocular hypertension, EUR 734.3 for glaucoma and EUR 1,054.9 for advanced glaucoma). Drugs and specialist consultations were by far the largest cost components. CONCLUSIONS: This study offers some information on the medical costs of glaucoma in Italy potentially useful for decision-making in the health care services. Health care resources and costs increased with disease severity. PMID- 17728559 TI - Inflammatory myofibroblastic tumor of the orbit. AB - The authors describe an unusual case of orbital inflammatory myofibroblastic tumor (IMT) in a 17-year-old patient who presented with a painful exophthalmos of the left eye. After complete surgical excision, the mass was diagnosed as an IMT based on morphological and immunohistochemical features. No tumor recurrence was evident during 28-month follow-up. The authors discuss histopathological and immunohistochemical characteristics and review the literature of orbital IMT. PMID- 17728558 TI - Indolent stage IE non-Hodgkin's lymphoma of the orbit: results after primary radiotherapy. AB - AIMS: Primary non-Hodgkin's lymphoma (NHL) of the orbit is uncommon, representing approximately 8% of extranodal NHLs. Twenty-two patients with indolent stage IE NHL were reviewed retrospectively to analyze the outcome and late effects of primary local radiotherapy. MATERIALS AND METHODS: The median age at first diagnosis was 63.5 years (range 24-82 years). Extranodal mucosa-associated lymphoid tissue lymphoma (n = 15) was the most common histological subtype of NHL, followed by follicular (n = 6) and lymphoplasmacytic lymphoma (n = 1). Radiotherapy was performed using a linear accelerator. The median radiation dose was 40 Gy (range 30-46 Gy). None of the patients received chemotherapy before irradiation. The follow-up period was 62 months (range 8-136 months). RESULTS: A complete response was achieved in all patients. The 5-year local control rate was 100%. Distant relapse occurred in 2 patients, resulting in a 5-year distant relapse-free survival rate of 88%. The 5-year overall survival rate was 89%; there were no lymphoma-related deaths. No serious acute complications (grade 3/4) were observed. Grade 1/2 late effects were documented in 44% of patients. Grade 3 complications (cataract: 2, dryness: 2) were observed in 4 patients (18%). CONCLUSIONS: Indolent early stage orbital NHL can be controlled with local radiotherapy. Morbidity is low. Regular follow-up examinations are necessary to detect rare cases of distant relapse. PMID- 17728560 TI - 'Mini-gauge' pars plana vitrectomy: 'inside-out view' with the GRIN solid rod endoscope. AB - PURPOSE: To stimulate the discussion about 'mini-gauge' pars plana vitrectomy. METHODS: Gradient index high-resolution endoscopy to analyze the 23- or 25-gauge access into the vitreous cavity. A total number of 66 pars plana interventions (almost 200 cannulas) were performed and recorded with the gradient index solid rod endoscope as well as through the microscope. RESULTS: Five main 'inside-out' observations were made through the endoscope. Some very slight rotating movement of the trocar was required to achieve a safe cannula implantation. Rotating the cannula too much could result in some unwanted side effects. The major amount of vitreous incarceration occurs during the implantation of cannulas. Incarcerated vitreous causes significant anterior-posterior vitreous traction. Intraocular cleaning of the port with the suction cutter releases the anterior-posterior traction without increasing the postoperative rate and degree of hypotony. Side effects like bleeding of the wound are likely to occur due to any sort of manipulation to the outside of the sclerotomy (i.e. cotton tips) other than the essential replacement of the conjunctiva. DISCUSSION: Surgeons who are considering the conversion to mini-gauge pars plana vitrectomy systems may be aided by endoscopic observations. PMID- 17728561 TI - Ptosis after intravitreal injection of triamcinolone acetonide: a retrospective case series. PMID- 17728562 TI - The tea ceremony: connecting with self and others. PMID- 17728563 TI - Night eating syndrome. AB - Night eating syndrome (NES), an eating disorder that has been linked to obesity, was first described in 1955. It occurs when the normally synchronous patterns of energy intake and sleep become disrupted; the result of this dysynchrony is a relative phase delay between the disordered eating patterns and the normal sleep wake cycles. Although specific criteria for NES have not yet been validated, the characteristic associated behaviors are evening hyperphagia, morning anorexia, and insomnia. This article reviews NES prevalence, behavioral and neurohormonal manifestations of this disorder, criteria for its differential diagnosis, and current treatment options. PMID- 17728566 TI - Predictors of self-reported health among older African-American central city adults. AB - Relationships between holistic factors and self-reports of health were examined. Ninety-two African-American older adults were sampled. Comorbid health conditions, higher pain intensity ratings, and more depressive symptoms were significantly related to lower self-rated health scores while age, marital status, education, and spiritual factors were not significantly related. PMID- 17728565 TI - Spiritual practice: a literature review related to spiritual health and health outcomes. AB - Spirituality and the expression of spirituality have received renewed interest in both nursing and nonnursing literature over the last 20 years. Scholars in spirituality studies have contributed to the wealth of both qualitative and quantitative data that exist. Spiritual practices that facilitate spiritual health are embedded within many nursing interventions. The purpose of this review is to provide an overview of empirical and associated nursing literature on spiritual practices. Definitions of spirituality and spiritual health are included, and theoretical underpinnings of the empirical literature are discussed. Relation of spiritual practice as a health behavior is presented with implications for future research identified. PMID- 17728568 TI - Critical incident technique utilization in research on holistic nurses. AB - This article describes the critical incident technique (CIT) as it informs holistic nursing. The CIT is a qualitative, systematic, open-ended technique for educing descriptive data from participants. It is an effective naturalistic tool for focusing participants on a specific event. The CIT is a user-friendly instrument that can foster reflection and promote personal expression. Holistic nursing is a personal and professional commitment to the healing process of self and others. The competency of holistic nurses revolves around their ability to incorporate the concepts and standards of the philosophy of holistic nursing into their life and practice. This article explores the use of the CIT in 2 separate studies on holistic nurses. Both studies utilized the CIT as a secondary source of data collection. All participants in both studies were members of the American Holistic Nurses Association. One study explored how experienced certified holistic nurses learned to become competent practitioners, while the other study focused on holistic nurses' experience with modalities, the perceived benefits to self and client. PMID- 17728567 TI - Sense of coherence among patients with cardiovascular disease and cancer undergoing surgery. AB - The sense of coherence (SOC) among patients undergoing cardiovascular surgery was compared with that of patients undergoing surgery for gynecological and oral cancer by using the Japanese version of the SOC questionnaire. The patients in the former group were able to cope with their disease and manage the relationship between their lifestyle and the disease for a long time. Eventually, however, they opted for surgery because they were unable to obtain life insurance if they did not resort to treatments other than medicine. On the other hand, the patients in the latter group had to suddenly deal with a very stressful event (being diagnosed with cancer and having had to undergo surgery). However, their malignant tumors were completely excised during surgery because their cancer was at an early stage. The analysis revealed that the average SOC score of the former group was significantly higher than that of the latter group; furthermore, the score of the latter group was similar to the SOC score of the general population. A multiple regression analysis revealed that the principal determinants of the SOC scores were the diagnosis of the patients (the duration of their struggle with the illness) and their employment status. The SOC of employed persons was higher than that of unemployed persons. PMID- 17728569 TI - The potential of the patient room to promote healing and well-being in patients and nurses: an integrative review of the research. AB - The purpose of this integrative review is to synthesize the existing research on the patient room in the acute care hospital as it pertains to the promotion, maintenance, or restoration of healing and well-being for patients. This review will describe 22 years of research in nursing, medicine, architecture, psychiatry, and environmental psychology that assesses the effectiveness of design features in the patient room used to promote healing. Research studies reviewed also include those that address the well-being in the nursing staff. Using strategies of integrative research review, 18 studies were reviewed. PMID- 17728570 TI - Green tea chings: on health, longevity, and a cup of humanity. PMID- 17728572 TI - A hospital's malicious criminal prosecution of a registered nurse. PMID- 17728575 TI - Toward a standardized and evidence-based continued competence assessment for registered nurses. PMID- 17728577 TI - Refusal of brain death diagnosis. PMID- 17728581 TI - Lessons in conducting an ethics consult. PMID- 17728580 TI - Conversations in ethics. PMID- 17728582 TI - Minors' rights in medical decision making. AB - In the past, minors were not considered legally capable of making medical decisions and were viewed as incompetent because of their age. The authority to consent or refuse treatment for a minor remained with a parent or guardian. This parental authority was derived from the constitutional right to privacy regarding family matters, common law rule, and a general presumption that parents or guardians will act in the best interest of their incompetent child. However, over the years, the courts have gradually recognized that children younger than 18 years who show maturity and competence deserve a voice in determining their course of medical treatment. This article will explore the rights and interests of minors, parents, and the state in medical decision making and will address implications for nursing administrators and leaders. PMID- 17728585 TI - Should neonatal palliative care take place at home, rather than the hospital? Pro. PMID- 17728586 TI - Should neonatal palliative care take place at home, rather than the hospital? Con. PMID- 17728587 TI - Fetal Concerns Program: a model for perinatal palliative care. AB - Advances in fetal diagnostics have resulted in families facing a pregnancy complicated by a fetal health concern. Perinatal literature supports that these families benefit from extensive counseling and education presented by a multidisciplinary team. In the program described in this article, perinatal palliative care planning is offered to families who have been told that their fetus has a potentially lethal prognosis. Called the "Fetal Concerns Program," it was developed to address the complex needs of families whose fetus has anomalies. This article reviews perinatal palliative care concepts and describes the Fetal Concerns Program's development as a perinatal palliative care service within a broader program. The special role of the nurse coordinator of the Fetal Concerns Program is highlighted. PMID- 17728588 TI - Providing pediatric palliative care: PACT in action. AB - High-quality pediatric palliative care should be an expected standard in the United States, especially since the publication of the numerous position statements such as "Precepts of Palliative Care for Children and Adolescents and Their Families," a joint statement created by the Association of Pediatric Oncology Nurses, the National Association of Neonatal Nurses, and the Society of Pediatric Nurses. Although many barriers still exist, dedicated individuals and teams strive to promote models of excellence and improve care for children with life-threatening conditions and their families. The Pediatric Advanced Care Team, a joint project of Dana-Farber Cancer Institute and Children's Hospital, Boston, is one such interdisciplinary pediatric palliative care consultation service. Founded in 1997, we have grown and learned from formal study and our extensive clinical work with families, children, and our colleagues. This article describes our journey as an interdisciplinary team forging a new service within two renowned medical institutions in which historically the primary emphasis of care has been on cure and innovation. Although these values remain, our work has resulted in an increased acceptance of balancing treatment of the underlying disease or condition along with treatment of the physical, psychosocial, and spiritual needs of the child and family through life or death. One of our goals is to help promote a balance of hope for cure with hope for comfort, dignity, and integrity for every child and family. PMID- 17728589 TI - Meaningful moments. AB - Rituals provide meaning and order to transitions, and symbolically connect people and events. Despite the prevalence of perinatal loss (miscarriage, stillbirth, and newborn death) and pediatric deaths, little has been written about the use of rituals surrounding these losses. The purpose of this article is to define the dimensions of a ritual as each pertains to perinatal and pediatric death, and provide concrete applications for use in clinical practice. Intention, participation, and meaning-making are the key dimensions of rituals that arise from clinical encounters. Initiating the discussion about ritual and the timing of the ritual itself are critical elements for the nurse who is caring for a bereaved family. Because of the paucity of research on using rituals in perinatal and pediatric death, nurse researchers should design studies that explore the outcomes of using rituals, both in the short- and long-term, following the death. PMID- 17728591 TI - End-of-life nursing education consortium for pediatric palliative care (ELNEC PPC). AB - Pediatric nurses must often care for children with life-threatening illness. Although the child may be a neonate with multiple organ failure, a young adolescent diagnosed with HIV, or a 7-year-old child involved in a serious bicycle accident, pediatric nurses are an essential part of the interdisciplinary team that plans, organizes, implements, and manages the care of these children and their families. To date, more than 600 pediatric nurses have attended a national End-of-Life Nursing Education Consortium-Pediatric Palliative Care (ELNEC-PPC) training program. Many of these nurses have returned to their institutions dedicated to making a difference in the palliative care provided to children and their families. Because pediatric palliative care education is so important, many trainers have incorporated ELNEC-PPC into their nursing orientation, annual competencies, and undergraduate and graduate nursing education. They are developing standards of care and serve on key hospital/hospice committees, such as policy, education, clinical care, and ethics committees. This article showcases various activities of ELNEC-PPC trainers and demonstrates their commitment to improve pediatric palliative care not only in their institutions but also on local, state, national, and international levels. PMID- 17728593 TI - Palliative care resources for the health professional. AB - Over the past several years, healthcare professionals have developed policies, guidelines, and educational programs to promote the implementation of pediatric palliative care practices in acute and outpatient care settings. This article provides a description and listing of many of these resources to aid nurses as they strive to improve their palliative care knowledge and skills, and implement palliative care programs in their institutions. PMID- 17728595 TI - Infant nutrition during palliative care. PMID- 17728594 TI - Tender mercies: increasing access to hospice services for children with life threatening conditions. AB - This article describes the initiation of the Children's Hospice and Palliative Care Coalition, an organization that emerged from the concern of two women for the unique needs of children with life-threatening conditions. The Coalition, based in California, was inspired to improve care for children with life threatening conditions and their families by the 2002 Institute of Medicine report When Children Die:... (which was printed in 2003: ). Its most recent work has been to advance legislative initiatives to develop, implement, and evaluate a pilot project waiver to provide a federally funded pediatric care benefit. PMID- 17728596 TI - Digital bereavement photography. PMID- 17728597 TI - Global pediatric palliative care. PMID- 17728603 TI - Assessing fetal well-being prior to cesarean birth. PMID- 17728604 TI - Effects of EMDR psychotherapy on 99mTc-HMPAO distribution in occupation-related post-traumatic stress disorder. AB - BACKGROUND: Post-traumatic stress disorder (PTSD) is a derangement of mood control with involuntary, emotionally fraught recollections that may follow deep psychological trauma in susceptible individuals. This condition is treated with pharmacological and/or cognitive therapies as well as psychotherapy with eye movement desensitization and reprocessing (EMDR). However, only a very limited number of studies have been published dealing with work-related PTSD, and investigations on the effect of treatment on cerebral blood flow represent an even smaller number. AIM: To investigate the short-term outcome of occupation related PTSD after EMDR therapy by 99mTc-HMPAO SPECT. METHOD: Fifteen patients, either train drivers suffering from PTSD after having been unintentionally responsible for a person-under-train accident or employees assaulted in the course of duty, were recruited for the study. 99mTc-HMPAO SPECT was performed on these patients both before and after EMDR therapy while they listened to a script portraying the traumatic event. Tracer distribution analysis was then carried out at volume of interest (VOI) level using a three-dimensional standardized brain atlas, and at voxel level by SPM. The CBF data of the 15 patients were compared before and after treatment as well as with those of a group of 27 controls who had been exposed to the same psychological traumas without developing PTSD. RESULTS: At VOI analysis significant CBF distribution differences were found between controls and patients before and after treatment (P=0.023 and P=0.0039, respectively). Eleven of the 15 patients responded to treatment, i.e., following EMDR they no longer fulfilled the DSM-IV criteria for PTSD. When comparing only the eleven responders with the controls, the significant group difference found before EMDR (P=0.019) disappeared after treatment. Responders and non-responders showed after therapy significant regional differences in frontal, parieto occipital and visual cortex and in hippocampus. SPM analysis showed significant uptake differences between patients and controls in the orbitofrontal cortex (Brodmann 11) and the temporal pole (Brodmann 38) both before and after treatment. A significant tracer distribution difference present before treatment in the uncus (Brodmann 36) disappeared after treatment, while a significant difference appeared in the lateral temporal lobe (Brodmann 21). CONCLUSION: Significant 99mTc-HMPAO uptake regional differences were found, mainly in the peri-limbic cortex, between PTSD patients and controls exposed to trauma but not developing PTSD. Tracer uptake differences between responders and patients not responding to EMDR were found after treatment suggesting a trend towards normalization of tracer distribution after successful therapy. These findings in occupational related PTSD are consistent with previously described effects of psychotherapy on anxiety disorders. PMID- 17728605 TI - Quantitative evaluation of very acute stage of complex regional pain syndrome after stroke using three-phase bone scintigraphy. AB - PURPOSE: Three-phase bone scintigraphy (TPBS) is an objective diagnostic test for complex regional pain syndrome (CRPS). The diagnostic importance of an increased uptake on the delayed phase has been proven in early CRPS, but that of the vascular and blood pool phases has not. The purpose of this study is to improve the diagnostic strength of the very acute stage of CRPS after stroke through a combined quantitative evaluation of each TPBS phase. METHODS: Quantitative TPBS analysis was performed in 26 post-stroke hemiplegic patients with very acute stage of CRPS and in 12 controls with no CRPS after brain lesion. Regions of interest (hands without fingers--carpal bones, metacarpal bones and metacarpopharyngeal joints) were selected and the count ratios of the affected to unaffected sides were calculated. RESULTS: The maximum values of control in each phase were used as the criteria of positive findings of each TPBS phase. Eleven patients in the vascular phase, 13 in the blood pool phase and 17 in the delayed phase had a higher assumption than the maximum values and a sensitivity of 42.3%, 50% and 65.4%, respectively. Twenty-one of 26 patients were interpreted as abnormal when at least one phase showed a positive finding. As a result, increased sensitivity of 80.8% and identical specificity of 100% were achieved. CONCLUSION: These findings suggest that the combination of quantitative evaluation of each TPBS phase can improve the diagnostic strength of the very acute stage of CRPS after stroke. PMID- 17728606 TI - Validation of a resolution-independent method for the quantification of 123I-FP CIT SPECT scans. AB - OBJECTIVE: To verify the applicability of a recently described resolution independent method for the semi-quantification of 123I-FP-CIT scans. METHODS: Visual interpretation, 'conventional' and resolution-independent semi quantification was performed on 60 123I-FP-CIT scans. Using ROC analysis, the results were compared to the final clinical diagnosis after a follow-up of at least 18 months. Sensitivity and specificity values were calculated and a cut-off value of the specific binding, which differentiated between normal and abnormal scans with high sensitivity and specificity, was given. RESULTS: Application of the resolution-independent method to a new set of 123I-FP-CIT SPECT data yielded a cut-off value of the specific striatal binding of 55 ml. Corresponding values of sensitivity and specificity were 95% and 72%, respectively. Further, based on the values of the area under the ROC curve and the 95% confidence interval of different semi-quantitative methods, the resolution-independent semi quantification agreed best with the final clinical diagnosis. CONCLUSION: We found a similar value of the specific 123I-FP-CIT binding as the one previously described in the literature, which proved the validity of the resolution independent method. Further, this method, among other 'conventional' semi quantitative methods, agreed best with the final clinical diagnosis. For this reason we recommend its use to aid in the diagnostic process. PMID- 17728607 TI - 99mTc(V)-DMSA SPECT for the assessment of disease activity in Graves' ophthalmopathy. AB - OBJECTIVE: The aim of this study was to evaluate the use of 99mTc(V) dimercaptosuccinic acid (99mTc(V)-DMSA) scintigraphy for the assessment of disease activity in patients with Graves' ophthalmopathy (GO) and compare their clinical parameters. METHODS: The study involved 20 patients who were clinically inactive and eight patients who were clinically active, a total 28 GO patients (18 female, 10 male; mean age: 39.2+/-13.4 years) and 12 control subjects (six female, six male; mean age: 57.12+/-12 years). Planar and SPECT orbital images were obtained 4 h after the intravenous injection of 555-740 MBq 99mTc(V)-DMSA, using low-energy, high-resolution, parallel-hole collimators with dual-head detectors. All SPECT data were reconstructed on conventional axial, sagittal and coronal projections using an iterative reconstruction. Semi-quantitative evaluation was performed comparing the orbital activity with nasal activity based on four grades. GO was classified according to the NOSPECS classification of the American Thyroid Association. Disease was considered clinically active if symptoms and signs deteriorated over 3 months. RESULTS: No significant correlation was detected between clinical activity and classification (P=0.192). However, clinical activity and 99mTc(V)-DMSA uptake were significantly correlated (P=0.0001). There was no correlation between the clinical classification and scintigraphic grading. Bilateral orbital index of the active group was significantly higher than that of the inactive group (P=0.0001). CONCLUSION: 99mTc(V)-DMSA imaging discriminates the active from inactive GO as well as showing an ongoing subclinical inflammation in the orbits of the patients with GO, regardless of the disease activity clinically. Our results revealed that 99mTc(V)-DMSA is a promising agent for the diagnosis of active Graves' ophthalmopathy. PMID- 17728608 TI - Influence of attenuation correction by integrated low-dose CT on somatostatin receptor SPECT. AB - AIM: Somatostatin receptor scintigraphy (SRS) is well-established in neuroendocrine tumour (NET) imaging. This study evaluated the impact of attenuation correction (AC) on SRS SPECT data in patients examined by SPECT-CT. METHODS: Planar scintigraphy and SPECT-CT of 17 patients (10 men, seven women; age, 40-74 years; mean, 62 years) suffering from NET were included. For the visual assessment of AC, the intensity and contrast of foci classified as pathological were rated in both the non-attenuation corrected (NAC) and the attenuation corrected (AC) SPECT images using a 5-point score. The change in signal intensity after AC was semiquantified two-fold for each focus in both SPECT(AC) and SPECT(NAC): firstly by using tumour-to-background (TB) ratios (defined as T(max)/B(mean)) for the determination of a TB(AC)/TB(NAC) ratio. Secondly, by a T(max,AC)/T(max,NAC) ratio. Both ratios were correlated to the focus depth. RESULTS: A total of 46 pathological foci were found. Focus contrast and intensity significantly increased in 14/46 foci (30%) after AC (mean, 3.7 4.0) in the visual analysis (P<0.001). While TB ratios increased only in 24/46 foci after AC and no correlation between the T(BAC)/T(BNAC) ratio and focus depth (r=0.027; P=0.856) was found, T(max) was higher after AC in all foci and the T(max,AC)/T(max,NAC) ratio showed the expected correlation to focus depth (r=0.650; P<0.01), indicating the superiority of the Tmax approach for the demonstration of the effects of attenuation correction on focal uptake. CONCLUSION: Attenuation correction of SRS SPECT data by SPECT-CT results in visually more clearly contrasted foci. Moreover, as focus intensity increases, especially in the more centrally localised foci, CT-based AC has a potential to further improve the sensitivity of SRS SPECT. PMID- 17728609 TI - Analysis of blood flow and glucose metabolism in mammary carcinomas and normal breast: a H2(15)O PET and 18F-FDG PET study. AB - OBJECTIVE: To determine parameters of perfusion, distribution coefficient, and glucose metabolism as part of the tumour-specific micromilieu of breast cancer and compare them with corresponding values in normal breast tissue. METHODS: H2(15)O PET and 18F-FDG PET were performed on 10 patients with advanced invasive ductal carcinomas of the breast. Perfusion, distribution coefficient, and glucose metabolism and standardized uptake were quantified and analysed. RESULTS: Mean values based on the regions of interest were 59.2+/-43.9 ml x min(-1) x 100 g(-1) (perfusion), 0.58+/-0.26 ml x g(-1) (distribution coefficient), 7.76+/-6.10 (standardized uptake), and 5.4+/-2.5 mg x min(-1) x 100 g(-1) (glucose metabolism). The corresponding values for normal breast tissue were 22.1+/-13.2 ml x min x 100 g(-1) (perfusion), 0.16+/-0.05 ml x g(-1) (distribution coefficient), 0.33+/-0.07 (standardized uptake), and 0.18+/-0.08 mg x min x 100 g(-1) (glucose metabolism). For each tumour-normal tissue parameter pair, the mean values were significantly higher in tumours than normal breast tissue. Region-of-interest and pixel-wise correlation analysis revealed a positive association between glucose metabolism and distribution coefficient and glucose metabolism and perfusion for 7/10 tumours investigated. CONCLUSIONS: H2(15)O PET and 18F-FDG PET were able to differentiate breast cancer and normal breast tissue. The pixel-wise analysis revealed information about the heterogeneity of tumour fine structure in perfusion, distribution coefficient, and glucose metabolism, which may provide important guidelines for improving individual treatment. PMID- 17728610 TI - FDG PET in lymphoma: the need for standardization of interpretation. An observer variation study. AB - OBJECTIVE: To measure and describe patterns of interobserver variation in visual interpretation of 18-FDG PET in malignant lymphoma. METHODS: Eleven nuclear medicine physicians with different levels of PET experience independently reviewed 37 18F-FDG PET scans of lymphoma patients (10 obtained at presentation, 27 during or after therapy). They were requested to identify and localize suspicious lymphoma sites and to assign a stage to the baseline scans, and to interpret the remaining scans for the presence of viable lymphoma. Individual (extra-)nodal regions were assessed for the likelihood of malignancy as positive, negative or equivocal. These results were compared to expert readings after dichotomization in conservative and sensitive reading classifications. RESULTS: Sixty-one percent and 56% (using sensitive and conservative reading, respectively) of the baseline scans were scored in accordance with the experts. Fourteen of the 27 scans obtained for therapy evaluation with viable tumour sites were scored in accordance with the experts in 82% and 94% of the patients, using conservative and sensitive reading, respectively. The 13 negative scans were scored in agreement with the experts in only 45% of the cases. False positivity pertained especially to the neck, periclavicular, axilla, mediastinum, lung and bone marrow. More experienced observers tended to have fewer false negative scores. CONCLUSION: There are substantial disparities among nuclear medicine physicians' interpretations of FDG PET scans of lymphoma patients, which may affect patient care and results of multi-institutional clinical trials. A well defined set of criteria is urgently needed to improve consistency. PMID- 17728611 TI - Merging molecular and anatomical information: a feasibility study on rodents using microPET and MRI. AB - OBJECTIVE: The use of the micro positron emission tomography (microPET) technique provides a powerful means for molecular imaging on small animals, while its inferior spatial resolution offers insufficient anatomical information which impedes the interpretations of the scans. To improve this limitation, it often relies on a clinical magnetic resonance imaging (MRI) for providing anatomical details. In this study, we designed and developed a new image co-registration platform which contains a stereotactic frame and external fiducial markers for microPET and MRI studies. The image co-registration accuracies were also validated by this new platform using various imaging protocols for microPET and MRI. METHODS: The microPET images were reconstructed by filtered back-projection (FBP) and ordered subset expectation maximization (OSEM) methods. Two MRI pulse sequences, two-dimensional T1-weighted fast spin-echo (FSE) and three-dimensional spoiled gradient recalled (SPGR), were employed in the studies. Two MRI scanning protocols were proposed for small animal imaging: the whole-body high-speed mode and the partial high-resolution mode. RESULTS: Reconstructed images from two different modalities were integrated by point-to-point registration via the external fiducials. Four inter-modality matched co-registration pairs (FBP-FSE, FBP-SPGR, OSEM-FSE, OSEM-SPGR) were obtained for both the high speed and high resolution modes. Co-registration accuracy was given as the average fiducial registration error (FRE) between the centroids of six markers from the registered images. The overall systemic FREs were about 0.50 mm. CONCLUSIONS: From the inter modality FRE comparison, MRI imaging with FSE performed better than that with SPGR sequence, due to its higher signal-to-noise ratio and less magnetic susceptibility effects. In the microPET perspective, the OSEM was superior to the FBP, as a result of fewer image artifacts. PMID- 17728612 TI - Improvement of semi-quantitative small-animal PET data with recovery coefficients: a phantom and rat study. AB - AIM: To evaluate the accuracy of semi-quantitative small-animal PET data, uncorrected for attenuation, and then of the same semi-quantitative data corrected by means of recovery coefficients (RCs) based on phantom studies. MATERIALS AND METHODS: A phantom containing six fillable spheres (diameter range: 4.4-14 mm) was filled with an 18F-FDG solution (spheres/background activity=10.1, 5.1 and 2.5). RCs, defined as measured activity/expected activity, were calculated. Nude rats harbouring tumours (n=50) were imaged after injection of 18F-FDG and sacrificed. The standardized uptake value (SUV) in tumours was determined with small-animal PET and compared to ex-vivo counting (ex-vivo SUV). Small-animal PET SUVs were corrected with RCs based on the greatest tumour diameter. Tumour proliferation was assessed with cyclin A immunostaining and correlated to the SUV. RESULTS: RCs ranged from 0.33 for the smallest sphere to 0.72 for the largest. A sigmoidal correlation was found between RCs and sphere diameters (r(2)=0.99). Small-animal PET SUVs were well correlated with ex-vivo SUVs (y=0.48x-0.2; r(2)=0.71) and the use of RCs based on the greatest tumour diameter significantly improved regression (y=0.84x-0.81; r(2)=0.77), except for tumours with important necrosis. Similar results were obtained without sacrificing animals, by using PET images to estimate tumour dimensions. RC-based corrections improved correlation between small-animal PET SUVs and tumour proliferation (uncorrected data: Rho=0.79; corrected data: Rho=0.83). CONCLUSION: Recovery correction significantly improves both accuracy of small-animal PET semi quantitative data in rat studies and their correlation with tumour proliferation, except for largely necrotic tumours. PMID- 17728613 TI - Intra-individual comparison of the human biodistribution and dosimetry of the D and L isomers of 2-[123I]iodo-phenylalanine. AB - PURPOSE: Several authors have shown in animal studies that D-enantiomeric amino acid analogues can have better tumour imaging properties compared to their L analogues. In our group, the D and L isomers of 2-[I]iodo-phenylalanine were identified as tumour-specific tracers in rat and mouse tumour models, with an advantage for the D-isomer. Here we compare, intra-individually, the normal biodistribution and dosimetry of both tracers in healthy human subjects. METHODS: Five male volunteers received both the L- and D-enantiomers, ranging from 84 to 114 MBq, with a 1 week interval between the tracers, allowing intra-individual comparison. Whole-body scans were performed and blood and urine samples were collected and analysed up to 24 h. Dosimetry was calculated using OLINDA 1.0 software. RESULTS: The biodistributions of the tracers are comparable as both show a moderate uptake in heart and the liver, a marked uptake in muscle tissue and clearance via the renal system. However, due to faster clearance, from 2.5 h, the uptake of the D-enantiomer was significantly lower compared to the L-isomer in all organs. The radiation dose estimations showed an effective dose of, respectively, 0.0120+/-0.0020 mSv x Bq(-1) and 0.0106+/-0.0038 mSv x Bq(-1) for 2 123I-L-Phe and 2-123I-D-Phe (P=0.18). In both cases the organ receiving the highest dose was the bladder wall. CONCLUSION: Both 2-123I-L-Phe and 2-123I-D-Phe show comparable moderate uptake in all organs. 2-123I-D-Phe is the more promising tracer, as it shows a faster clearance resulting in a lower dose and a lower background, favouring tumour imaging with respect to the tumour/background ratio. PMID- 17728616 TI - Pockets of pancreatitis. PMID- 17728617 TI - Changing i.v.s: kids are different. PMID- 17728621 TI - Five flaws in drug delivery. PMID- 17728628 TI - What you need to know about PICCs, part 2. PMID- 17728629 TI - Eyeing capnography to improve PCA safety. PMID- 17728630 TI - Finding Spanish patient-education materials online. AB - Here's a quick guide to reliable-and free-patient-education handouts. PMID- 17728634 TI - How herbal products increase surgical risks. PMID- 17728635 TI - The VA leads the way in electronic innovations. PMID- 17728636 TI - Understanding wound dehiscence. PMID- 17728650 TI - Getting misty over wound care. Learn how therapy with ultrasound waves and saline mist can help your patient's wound heal. PMID- 17728651 TI - Choosing the right vascular access device. PMID- 17728652 TI - Taking charge of seizure activity. PMID- 17728654 TI - Protecting patients from harm: reduce the risks of high-alert drugs. PMID- 17728659 TI - Administering pneumococcal vaccine. PMID- 17728660 TI - Facing up to withdrawal from topical steroids. PMID- 17728662 TI - Autonomic dysreflexia. PMID- 17728663 TI - Serotonergic candidate genes and puerperal psychosis: an association study. AB - BACKGROUND: Altered serotonergic function is implicated in the aetiology and pathogenesis of a host of psychiatric disorders, and structural variations/polymorphisms in genes encoding the serotonin transporter and various serotonin receptor subtypes are attractive candidates to investigate the biological component underlying these disorders. Specific phenotypic subtypes, that perhaps represent homogeneous forms of the disorder, may increase the power to detect genes in complex diseases. OBJECTIVE: We investigated regulatory and functional polymorphic DNA markers of serotonergic candidate genes using a case control approach in puerperal psychosis and bipolar affective disorder probands. METHODS: We genotyped 320 female participants (104 puerperal psychosis probands, 102 bipolar disorder participants and 114 controls) at the serotonin transporter SERT (5-HTT) 5-HTTVNTR and 5-HTTLPR locus; serotonin receptor 2A (5-HT2A)-T102C and His452Tyr loci, the serotonin receptor 2C (5-HT2C)-Cys23Ser locus, and seven unrelated Alu polymorphic markers. RESULTS: We observed an association of the puerperal psychosis phenotype with the allele 10 of 5-HTTVNTR of SERT (P=0.004) and a modest association with the genotypic frequencies of the 5-HTTLPR (P=0.036). A nominal P value of 0.006 was observed with the S-10 haplotype in the PP group as compared with bipolar affective disorder probands. Significant association was observed with bipolar affective disorder phenotype with Tyr allele of the 5-HT2A His452Tyr gene polymorphism (P=0.00043) even after a conservative multiple test correction. No association was observed, however, with the 5-HT2A T102C locus, and the distribution of the other seven Alu markers did not differ between the groups. CONCLUSION: The association between polymorphisms in serotonergic genes (SERT and 5-HT2A, 5-HT2C) suggests that these genetic factors can modulate vulnerability to puerperal psychosis in female bipolar participants. PMID- 17728664 TI - The association between delirium and the apolipoprotein E epsilon4 allele in the elderly. AB - OBJECTIVE: As not all patients with similar risk factors and eliciting conditions develop delirium; it may be hypothesized that genetic variation may play a role in the risk of delirium. On the basis of the relationship between dementia, respectively reduced cholinergic activity, and the APOE epsilon4-allele, and the similarities between dementia and delirium in reduced cholinergic activity, the APOE epsilon4-allele is a rational candidate-gene for delirium. This study examined the association between APOE epsilon4-allele and delirium in elderly patients. METHODS: Acutely admitted patients to the Department of Medicine of 65 years and over were included during a 27-month time period. Delirium was scored by the confusion assessment method. Cognitive impairment was diagnosed by Mini Mental State Examination and informant questionnaire on cognitive decline. Genotyping was done with matrix-assisted laser-desorption/ionization time-of flight mass spectrometry. RESULTS: Of 415 included patients, a random sample of 264 patients was genotyped for APOE. The patients who met the criteria for delirium (35%) were significantly older and more frequently had preexisting functional and cognitive impairment. APOE genotype was borderline significantly associated with cognitive impairment in patients below 75 years (P=0.057). The odds ratio for carriers of an APOE epsilon4-allele compared with patients without an APOE epsilon4-allele for developing delirium was 1.17 (95% confidence interval (CI): 0.49-2.78) in the cognitively intact patients and 0.42 (95% CI: 0.14-1.30) in the cognitively impaired patients. No relation existed between the total number of APOE epsilon4-alleles and the different delirium subtypes (P=0.12). CONCLUSIONS: We found no convincing evidence that carriers of the APOE epsilon4 allele have a higher risk of delirium. PMID- 17728665 TI - Is 472G/A catechol-O-methyl-transferase gene polymorphism related to panic disorder? AB - OBJECTIVES: Case-control studies relating 472G/A catechol-O-methyl-transferase polymorphism with the risk of developing panic disorder showed inconclusive or contradictory results. To shed some light on these results a meta-analysis of all available case-control studies was conducted. METHODS: We searched PubMed database for English-languages case-control studies using the key words: Catechol O-methyl-transferase and panic. Case-control studies that determined the distribution of 472G/A genotypes in cases with primary and predominant panic disorder, and in controls free of psychiatric disorders were eligible for inclusion in the meta-analysis. The pooled risk effect (odds ratio, OR) was estimated using fixed effects and random effects (RE) models. The heterogeneity between studies was tested using the Q-statistic, heterogeneity was also quantified with the I metric. Possible sources of bias were also explored. RESULTS: The main analysis for investigating the association of the allele G and the risk of developing panic disorder relative to the allele A, showed significant heterogeneity (PQ<0.01, I=79%) between studies, then the RE OR was nonsignificant, heterogeneity OR=1.04 with 95% confidence interval (0.71-1.53). Although for both sexes the OR was not significant, there is evidence that in females the risk of PD [RE OR=1.07 (0.54-2.11)] was greater than in males [RE OR=0.86 (0.53-1.39)]. Inconsistency in genetic effects between East Asians [RE OR=0.73 (0.41-1.30) and (PQ=0.03, I=73%)] and Caucasians [OR=1.26 (0.93-1.69) and (PQ=0.24, I=28%)] existed. The genotype differences for the homozygotes, the recessive and dominant models for allele G produced the same overall pattern like the allele contrast in terms of association and heterogeneity. No differential magnitude of effect in large versus small studies for each polymorphism investigating was found. The cumulative meta-analysis showed an increase in OR as evidence accumulated. CONCLUSIONS: No conclusive evidence showing that 472G/A polymorphism is a reliable marker for panic disorder was found; moreover, large heterogeneity between studies existed. Large and more rigorous association studies investigating also the interaction with other genetic/environmental factors might provide more conclusive evidence. PMID- 17728667 TI - Novel procedure for genotyping of the human serotonin transporter gene-linked polymorphic region (5-HTTLPR)--a region with a high level of allele diversity. AB - BACKGROUND: The serotonin transporter, the target of a group of antidepressant drugs, is involved in the regulation of the availability and reuptake of serotonin. A variable number of tandem repeats in the promoter region of the serotonin transporter gene, designated 5-HTTLPR, affects the transcription of this gene and appears to modulate the susceptibility to a variety of diseases including depression. Of importance, 5-HTTLPR alleles composed of the same number of basic units may differ at single nucleotide positions providing an additional source of variation. OBJECTIVE: To develop a procedure for detailed genotyping of 5-HTTLPR based upon simultaneous analysis of tandem repeat size variation and single nucleotide variations. METHODS: We elaborated a list of all known 5-HTTLPR alleles to provide an overview of the allele repertoire at this polymorphic locus. Fragments of 5-HTTLPR were PCR-amplified in reaction mixtures prepared with and without 7-deaza-dGTP. The amplified fragments were treated with NciI and NlaIII and subjected to agarose gel electrophoresis. Alleles were identified by comparison of the observed electrophoretic patterns with the predicted patterns. Two hundred samples of human genomic DNA representing a variety of different 5 HTTLPR alleles were included in the study. MAIN RESULTS: We were able to amplify fragments of 5-HTTLPR, which are GC-rich, without the use of 7-deaza-dGTP. This is an advantage as modified nucleotides may inhibit restriction enzymes and interfere with allele determination. After having developed a 5-HTTLPR genotyping assay, we examined all samples of DNA in two separate rounds of analyses and found complete agreement between the results from these two rounds. CONCLUSION: On the basis of simultaneous analysis of tandem repeat size variation and variation of single nucleotides we designed a reliable assay for the determination of the major alleles and several of the rare alleles at the polymorphic locus 5-HTTLPR. PMID- 17728666 TI - Sequence variation in DOCK9 and heterogeneity in bipolar disorder. AB - BACKGROUND: Linkage of bipolar disorder to a broad region on chromosome 13q has been supported in several studies including a meta-analysis on genome scans. Subsequent reports have shown that variations in the DAOA (G72) locus on 13q33 display association with bipolar disorder but these may not account for all of the linkage evidence in the region. OBJECTIVE: To identify additional susceptibility loci on 13q32-q33 by linkage disequilibrium mapping and explore the impact of phenotypic heterogeneity on association. METHODS: In the initial phase, 98 single nucleotide polymorphism (SNPs) located on 13q32-q33 were genotyped on 285 probands with bipolar disorder and their parents were drawn from families in the NIMH Genetics Initiative consortium for bipolar disorder (NIMH1 4) and two other series. Fine scale mapping using one family series (NIMH1-2) as the test sample was targeted on a gene that displayed the highest evidence of association. A secondary analysis of familial component phenotypes of bipolar disorder was conducted. RESULTS: Three of seven SNPs in DOCK9, a gene that encodes an activator of the Rho-GTPase Cdc42, showed significant excess allelic transmission (P=0.0477-0.00067). Fine scale mapping on DOCK9 yielded evidence of association at nine SNPs in the gene (P=0.02-0.006). Follow-up tests detected excess transmission of the same allele of rs1340 in two out of three other sets of families. The association signals were largely attributable to maternally transmitted alleles (rs1927568: P=0.000083; odds ratio=3.778). A secondary analysis of familial component phenotypes of bipolar disorder detected significant association across multiple DOCK9 markers for racing thoughts, psychosis, delusion during mania and course of illness indicators. CONCLUSION: These results suggest that DOCK9 contributes to both risk and increased illness severity in bipolar disorder. We found evidence for the effect of phenotypic heterogeneity on association. To our knowledge this is the first report to implicate DOCK9 or the Rho-GTPase pathway in the etiology of bipolar disorder. PMID- 17728668 TI - Evidence for two schizophrenia susceptibility genes on chromosome 22q13. AB - OBJECTIVE: Previous linkage scans and meta-analyses for schizophrenia susceptibility loci failed to include the most distal portion of chromosome 22q. Accordingly, 27 families having individuals affected with schizophrenia and schizophrenia-spectrum disorders were analyzed using a set of highly informative markers covering all of chromosome 22q. METHODS: Microsatellite and single nucleotide polymorphism markers were evaluated by nonparametric linkage, parametric linkage, and transmission disequilibrium testing of 22q. RESULTS: The maximum nonparametric logarithm of odd scores were 2.9 (P=0.0016) for schizophrenia and 2.7 (P=0.003) for a broader disease definition that included schizotypal personality disorder-both at 44.5 cM within the Sult4A1 locus. Parametric models assuming dominant modes of inheritance and genetic heterogeneity gave maximum multipoint logarithm of odd scores for the broader disease definition at the Sult4A1 locus of 3.3 (P=0.0006) and single point logarithm of odd scores of 3.1-4.8 for Sult4A1 markers (P=0.000015-0.0005). A distal locus, centered at 61 cM, shows a maximum nonparametric logarithm of odd scores of 1.5 (P=0.072) for the broader disease definition. Transmission disequilibrium testing for three adjacent microsatellite markers located near the distal linkage peak revealed significant values for marker D22s526 for schizophrenia (P=0.0016-0.14) and for broader disease definitions including schizotypal personality disorder (P=0.0002-0.0003), and both schizotypal personality disorder plus schizoaffective disorder (P=0.00001-0.000077). CONCLUSION: At least two separable, but closely linked, loci within 22q13 influencing susceptibility to schizophrenia-spectrum disorders, might be possible. PMID- 17728669 TI - Association analysis of 15 polymorphisms within 10 candidate genes for antisocial behavioural traits. AB - This study sought to test 15 simple sequence repeat polymorphisms within 10 candidate genes for association with antisocial behavioural traits. Genes included were those known to regulate dopamine synthesis and transmission in the brain (DBH, DRD2, MAOA, TFAP2B, NR4A2, LMX1B) and those involved in the differentiation of social and sexual behaviour in men and women (AR, ESR1, OXTR, AVPR1A). Participants were Caucasians (men=1007, women=1089) aged 20-24 years who were assessed for indicators of antisocial traits such as pseudo-maturity, substance misuse and unstable lifestyle. Significant associations for antisocial traits were found with AR and ESR1 polymorphisms in men, and with polymorphisms within NR4A2 and TFAP2B in women. The association with TFAP2B remained significant after correction for multiple testing. This pattern of associations suggests that genetic variation within transcription factors may in part explain the variation observed in the population for antisocial behavioural phenotypes. PMID- 17728670 TI - Single nucleotide polymorphism analysis of corticotropin-releasing factor-binding protein gene in bipolar disorder. AB - Corticotropin-releasing factor-binding protein regulates the availability of free corticotropin-releasing factor and is a functional candidate gene for affective disorders. The aim of this study was to examine the association between polymorphisms in CRF-BP gene and bipolar disorder in an isolated Swedish population. One hundred and eighty-two patients with bipolar I disorder and 333 controls from Northern Sweden were included in the study. Five single nucleotide polymorphisms and a deletion polymorphism in the CRF-BP gene were genotyped. The haplotype block structure of the gene was considered and the expectation maximization algorithm was adopted to estimate the haplotype frequencies. As a result, there were no significant associations of the different polymorphisms in the CRF-BP gene with bipolar disorder. In conclusion, this study in an isolated Swedish population does not support a role for the CRF-BP gene in the vulnerability for bipolar disorder. PMID- 17728671 TI - Possible association between genetic variants at the GRIN1 gene and schizophrenia with lifetime history of depressive symptoms in a German sample. AB - Genetic variation in glutamatergic signalling pathways is believed to play a substantial role in the aetiology of schizophrenia. The N-methyl-D-aspartate receptor subunit gene GRIN1 has been proposed as a candidate gene for schizophrenia. We tested for a potential association between schizophrenia and four single nucleotide polymorphisms (rs4880213, rs11146020, rs6293, and rs10747050) and one microsatellite marker at GRIN1 in a German sample of 354 patients and 323 controls. We found significant associations in single-marker and haplotype-based analyses (P<0.05). Significance was more pronounced (P<0.01) in the subset of patients with a lifetime history of major depression, a subgroup of schizophrenia described previously as a promising phenotypic subtype in genetic studies of schizophrenia. Although significances did not withstand correction for multiple testing, the results of our exploratory analysis warrant further studies on GRIN1 and schizophrenia. PMID- 17728672 TI - ZDHHC8 single nucleotide polymorphism rs175174 is not associated with psychiatric features of the 22q11 deletion syndrome or schizophrenia. PMID- 17728673 TI - No association between polymorphisms of DAO and DAOA genes and homicidal behaviors in Korean schizophrenia. PMID- 17728674 TI - Association study of GOT2 genetic polymorphisms and schizophrenia. PMID- 17728675 TI - What impact does spinal deformity correction for adolescent idiopathic scoliosis make on quality of life? AB - STUDY DESIGN: : Literature review. OBJECTIVE: : To identify scientifically sound studies that have reported changes in quality of life (QOL) after spinal deformity correction in patients with adolescent idiopathic scoliosis (AIS) and to discuss these findings. SUMMARY OF BACKGROUND DATA: : Few studies have been published. Most are retrospective cohort studies and lack both preoperative and postoperative data for the outcome in terms of QOL. METHODS: : A review of existing literature with the emphasis on spinal fusion for AIS and outcome as measured by health-related QOL was performed. RESULTS: : Thirteen studies of various quality were found after reviewing the papers. Only 3 of them contained both preoperative and postoperative data on QOL, using the SRS-22/-24. They all reported a statistically significant improvement in some of the domain scores. The clinical implications of these findings are unclear, as the minimal clinically important differences for SRS-22/-24 have not yet been established. CONCLUSION: : Weak evidence (Level IV) exists in the literature that spinal deformity correction for AIS does not significantly impact QOL in short-term or mid-term. The interpretation of this must be that there were no serious adverse events after surgery. PMID- 17728676 TI - Evidence-based medicine analysis of all pedicle screw constructs in adolescent idiopathic scoliosis. AB - STUDY DESIGN: : Focus paper. OBJECTIVE: : To evaluate the current evidence-based medicine (EBM) literature in the use of pedicle screw constructs in patients with adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND: : EBM has evolved over the past 20 years to provide a framework for the evaluation of therapy and the application of that assessment to a particular patient or a disease. Application of EBM analysis to spinal instrumentation, and specifically to pedicle screw constructs, is challenging. METHODS: : Cochrane database, Ovid Medline, and PubMed were searched using the terms "pedicle screws" and "adolescent idiopathic scoliosis." The reference list of the major papers by authors Lenke, Suk, and Kim were hand searched. Relevant articles were retained if they described a pedicle screw construct to correct AIS or compared pedicle screw constructs with another technique. Articles that did not have patients with adolescent idiopathic scoliosis in their subject groups or did not use pedicle screws as a part of their deformity correction were excluded from the study. RESULTS: : Based on the search strategy described above, 40 articles met the inclusion criteria and were selected for review in this manuscript. Of these, 32 studies are retrospective reviews including 2 studies that do not define their data collection technique. Six studies have a prospective study design, 1 is a case report, and 1 is a cadaveric study. CONCLUSION: : In the absence of evidence from randomized trials, surgeons must rely on the best available information to guide patient management decisions. Although there have been many publications on the topic of all pedicle screw constructs in AIS, evidence regarding the advantage of all pedicle screw constructs remain limited to case series, biomechanical studies, and expert opinions. PMID- 17728677 TI - Evidence based medicine: analysis of Scheuermann kyphosis. AB - STUDY DESIGN: : A review of the current literature using evidence-based medicine (EBM) regarding etiology, natural history, and treatment of Scheuermann kyphosis. OBJECTIVE: : To provide current concepts for the rational evaluation and treatment of Scheuermann kyphosis supported by EBM. SUMMARY OF BACKGROUND DATA: : The literature concerning etiology, natural history, and treatment of Scheuermann disease has mixed views and recommendations, most of which are not strongly supported with levels of evidence. METHODS: : A thorough database search was performed in order to obtain the best current information and levels of evidence on etiology, natural history, and treatment options for Scheuermann kyphosis based on EBM criteria. RESULTS AND CONCLUSION: : Scheuermann kyphosis is the most common cause of hyperkyphosis in adolescence. Its true etiology remains unknown, but there appears to be a strong genetic as well as an environmental contribution. The kyphotic deformity is frequently attributed to "poor posture" resulting in delayed diagnosis, and treatment indications remain debated because the natural history has not been clearly defined. When recognized early in adolescence with progressive kyphosis, bracing treatment will usually result in modest correction of the deformity. Symptomatic adolescents with severe deformity have demonstrated significant deformity correction following surgical intervention; however, clinical outcomes data are not yet available, and the studies available do not have strong levels of evidence. PMID- 17728678 TI - Does spinal fusion influence quality of life in neuromuscular scoliosis? AB - STUDY DESIGN: : Systematic literature review of articles pertaining to quality of life (QOL) in neuromuscular scoliosis patients that underwent spinal fusion. OBJECTIVE: : To determine if QOL is improved by scoliosis surgery in neuromuscular patients. SUMMARY OF BACKGROUND DATA: : The primary focus of most prior studies on neuromuscular scoliosis has been on the technical correction of spinal deformities, and not the child's postoperative performance and function in activities of daily living. METHODS: : Computer-based English literature search of Google and PubMed databases. RESULTS: : A total of 198 publications in the English literature between 1980 and 2006 were identified from a PubMed and Google Scholar search of QOL in neuromuscular scoliosis patients that underwent spinal fusion. CONCLUSION: : Spinal fusion improves QOL in CP (Grade C recommendation). Spinal fusion improves QOL in muscular dystrophy (Grade C recommendation). Spinal fusion does not improve QOL in spina bifida (Grade C recommendation). PMID- 17728679 TI - Evidence-based medicine analysis of isthmic spondylolisthesis treatment including reduction versus fusion in situ for high-grade slips. AB - STUDY DESIGN: : Literature review. OBJECTIVES: : The purpose of this article is to review the available literature and to attempt to formulate evidence-based recommendations for the surgical treatment of high-grade spondylolisthesis in the pediatric population. SUMMARY OF BACKGROUND DATA: : The surgical management of high-grade spondylolisthesis remains controversial due to the lack of high level evidence. Prospective randomized studies have not been completed. METHODS: : Through an electronic database search and published literature cross-reference, appropriate studies were identified and assigned the appropriate level of evidence. RESULTS: : There were no Level I or II evidence on this topic with our search. The best level of evidence that we have on this topic is retrospective comparative studies. We found 5 such articles which compared fusion in situ to reduction and fusion for high-grade spondylolisthesis. Pseudarthrosis rates are decreased by performing an instrumented reduction with a fusion. However, there is no significant difference in a clinical outcome of patients treated in situ versus reduction. CONCLUSION: : Because of the paucity of high levels of evidence, we are not able to formulate clear guidelines for treatment of high grade spondylolisthesis based on the best evidence available in the published literature. PMID- 17728680 TI - A systematic literature review of nonsurgical treatment in adult scoliosis. AB - STUDY DESIGN: : A formal systematic review of the literature for conservative treatment of adult deformity was performed. OBJECTIVE: : To evaluate evidence for the efficacy and effectiveness of proposed conservative treatment options in adult deformity. SUMMARY OF BACKGROUND DATA: : Adult deformity is a major demographic health issue in the geriatric population in both the United States and the world communities. Surgeons are often very conservative in the treatment of adult scoliosis because of the complication rates associated with the surgeries and the marginal bone quality endemic to this population. A prerequisite to surgical intervention is usually failure of all appropriate conservative care. There is currently a lack of consensus on the most efficacious conservative treatments for adult deformity. METHODS: : A systematic review of clinical studies; using the key terms of adult or degenerative and scoliosis combined with any of the following: bracing, casting, physical therapy, chiropractic, and injections for treatment. The database inclusions were PubMed, OVID, and CINAHL: Articles were excluded if the primary patient populations were adolescents or the treatment options performed were primarily surgical. The methodology of the studies was graded and the evidence was classified into 1 of 5 levels based on study types. Based on this, a treatment recommendation was determined. RESULTS: : There is indeterminate, Level III/IV evidence on the effectiveness of any conservative care option. Specifically, there is Level IV evidence on the role of physical therapy, chiropractic care, and bracing. There is Level III evidence for injections in the conservative treatment of adult deformity. There is insufficient research for a treatment recommendation beyond Level 2c very weak evidence, but the available literature is supportive of further clinical research in conservative care as a treatment in adult deformity. CONCLUSION: : Conservative care in general may be a helpful option in the care of adult deformity, but evidence for this is lacking. Unfortunately, no treatment option within conservative care has support within the literature as a preferred solution. Basic clinical research at any level would be helpful to further clarify the options. PMID- 17728681 TI - The problems and limitations of applying evidence-based medicine to primary surgical treatment of adult spinal deformity. AB - STUDY DESIGN: : Assessment of peer-reviewed literature and personal experience with publications and grant organization. OBJECTIVE: : This is an analysis of the current status of evidence-based medicine for primary adult spinal deformity to answer the question of whether surgical treatment benefits patients. SUMMARY OF BACKGROUND DATA: : A limited number of evidence-based studies have been performed for primary adult scoliosis and spinal deformity surgery. None of these studies is ideal. METHODS: : This is an assessment of current literature and study group methodology in an attempt to provide an evidence-based medicine approach for the study of primary presentation adult scoliosis and related spinal deformity. RESULTS: : Many reasonable studies exist; however, there are no current definitive studies that answer the question posed above. There are many obstacles, both financial and organizational, to producing an "ideal" study. Most smaller studies suggest that surgical treatment of primary adult scoliosis benefits the patient. However, there is no multicenter prospective randomized study to answer this question. CONCLUSION: : A multicenter funded study is needed to answer appropriate questions. PMID- 17728682 TI - Scoliosis Research Society endorsement of Focus issue on evidence-based medicine. PMID- 17728683 TI - Evidence-based medicine summary statement. PMID- 17728684 TI - Introduction to and techniques of evidence-based medicine. AB - STUDY DESIGN: : Literature review. OBJECTIVE: : To outline the components and application of evidence-based medicine (EBM) with an emphasis on the critical components of conduct and appraisal of clinical research. SUMMARY OF BACKGROUND DATA: : "Evidence-based medicine" is now a commonplace phrase representing the hallmark of excellence in clinical practice. EBM integrates a question, thoughtful comprehensive evaluation of the pertinent literature, with clinical experience and patient preference to make optimal patient care decisions. These decisions must be evaluated with objective outcome measures to ensure effectiveness. There have been some misconceptions around the application of EBM and that it is synonymous with randomized controlled trials (RCTs) or based purely on levels of evidence. METHODS: : Narrative and review of literature. CONCLUSION: : Clinicians must understand the importance of the research question, study design, and outcomes in order to apply the best available research to patient care. Treatment recommendations evolving from critical appraisal are not only based on levels of evidence, but the risk benefit ratio and cost. The true philosophy of EBM, however, is not for research to supplant individual clinical experience and the patient's informed preference, but to integrate them with the best available research. Healthcare professionals and administrators must grasp that EBM is not a RCT. They must realize that the question being asked and the research circumstances dictate the study design. Furthermore, they must not diminish the role of clinical expertise and informed patient preference in EBM. PMID- 17728685 TI - Developing outcome measures for pediatric deformity surgery. AB - STUDY DESIGN: : Review article regarding the development of outcome measures for pediatric spinal deformity. OBJECTIVE: : To discuss the role of patient-based outcomes and process measures in pediatric spinal deformity patients. SUMMARY OF BACKGROUND DATA: : A number of health-related quality of life (HRQOL) questionnaires assess, from patients' perspectives, the effectiveness of spinal deformity correction. The SRS instrument is the most prominent HRQOL tool used in North American adolescent scoliosis studies today. However, these patient-based outcomes and perceptions do not necessarily correlate with process measurements, particularly in the area of increase spinal deformity correction being achieved with newer, more powerful, pedicle screw instrumentation. Furthermore, spinal deformity presenting during infancy or early childhood poses a particular challenge for developing useful evidence-based outcomes tools. METHODS: : The rationale for patient-based outcome development in pediatric spinal deformity is discussed, along with its important association with process measures. RESULTS: : Newer HRQOL tools are under development that may better recognize and differentiate changes in adolescent patients' appearances before and after surgery. For early-onset spinal deformity patients, newer process measures for periodic outcome assessment, such as volume measurement of lung parenchyma and spine/chest cage measurement, are being developed. CONCLUSION: : Ultimately, both patient and process measures are necessary to fully evaluate the results of pediatric spinal deformity surgery. PMID- 17728686 TI - Evidence basis for management of spine and chest wall deformities in children. AB - STUDY DESIGN: : Review of relevant studies, including levels of evidence. OBJECTIVE: : To review research on growth of the spine and chest wall and treatment of deformities. To place this knowledge in context of evidence-based assessment. SUMMARY OF BACKGROUND DATA: : Knowledge of the growth of the spine, chest wall, and lung in the normal and deformity states has evolved among independent specialties over the past 60 years. Interest in the interrelationship has blossomed as more tools for assessment and treatment have developed. Spine based and chest wall-based treatment options now exist, as well as options of resection versus gradual distraction. METHODS: : Peer-reviewed research published on the growth of the spine, lung, chest wall, and treatment of their deformities was reviewed. Treatment methods and outcomes were compared. Ranking of the levels of evidence was performed where possible. RESULTS: : Most studies of these topics are Level III and IV studies, consisting of case-control studies and case series. This limitation arises because of the rarity and heterogeneity of the disorders affecting the growing spine and chest wall. The natural history of most types of spinal/chest wall deformities is not known with accuracy. Some experimental evidence informs the treatments which involve modulation of the growth of the spine. However, accurate models of the deformities themselves are lacking. Improvements in imaging and measurement offer options for more accurate patient comparison. CONCLUSION: : The natural history and results of treatment of deformities of the spine and chest wall offer much opportunity for further evidence-based research. PMID- 17728687 TI - Surgical rates after observation and bracing for adolescent idiopathic scoliosis: an evidence-based review. AB - STUDY DESIGN: : Systematic review of clinical studies. OBJECTIVES: : To develop a pooled estimate of the prevalence of surgery after observation and after brace treatment in patients with adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: : Critical analysis of the studies evaluating bracing in AIS yields limited evidence concerning the effect of TLSOs on curve progression, rate of surgery, and the burden of suffering associated with AIS. Many patients choose bracing without an evidence-based estimate of their risk of surgery relative to no treatment. Therefore, such an estimate is needed to promote informed decision making. METHODS: : Multiple electronic databases were searched using the key words "adolescent idiopathic scoliosis," "observation," "orthotics," "surgery," and "bracing." The search was limited to the English language. Studies were included if observation or a TLSO was evaluated and if the sample closely matched the current indications for bracing (skeletal immaturity, age <15 years, Cobb angle between 20 degrees and 45 degrees ). One reviewer (L.A.D) selected the articles and abstracted the data, including research design, type of brace, minimum follow-up, and surgical rate. Additional data concerning inclusion criteria and risk factors for surgery included gender, Risser, age and Cobb angle at brace initiation, curve type, and dose (hours of recommended brace wear). RESULTS: : Eighteen studies were included (observation = 3, bracing = 15). All were Level III or IV clinical series. Despite some uniformity in surgical indications, the surgical rates were extremely variable, ranging from 1 surgery of 72 patients (1%) to 51 of 120 patients (43%) after bracing, and from 2 surgeries of 15 patients (13%) to 18 of 47 patients (28%) after observation. When pooled, the bracing surgical rate was 23% compared with 22% in the observation group. Pooled estimates for surgical rate by type of brace, curve type, Cobb angle, Risser sign, and dose were also calculated. CONCLUSION: : Comparing the pooled rates for these two interventions shows no clear advantage of either approach. Based on the evidence presented here, one cannot recommend one approach over the other to prevent the need for surgery in AIS. This recommendation carries a grade of D, indicating that the use of bracing relative to observation is supported by "troublingly inconsistent or inconclusive studies of any level." The decision to brace for AIS is often difficult for clinicians and families. An evidence-based estimate of the risk of surgery will provide additional information to use as they weigh the costs and benefits of bracing. PMID- 17728688 TI - Re: Cochlear implantation for hearing loss associated with bilateral endolymphatic sac tumors in von Hippel-Lindau disease. PMID- 17728689 TI - Pulsatile tinnitus. PMID- 17728690 TI - Relationship Between Dynamic Balance and Self-Reported Handicap in Patients Who Have Unilateral Peripheral Vestibular Loss. AB - OBJECTIVE:: The purpose of this study was to investigate whether Dizziness Handicap Inventory (DHI) score is related to postural performance as assessed by dynamic posturography. STUDY DESIGN:: Retrospective study. SETTING:: Outpatient in a tertiary referral center. PATIENTS:: Ninety-two complete unilateral vestibular loss patients, categorized into 3 groups according to the postlesion stage: 1 to 2 months (n = 32; age, 47.6 +/- 10.7 yr), 4 to 7 months (n= 23; 47.1 +/- 8.37 yr), and 1 year and older (n = 37; 49.2 +/- 9.5 yr). MAIN OUTCOME MEASURES:: Dizziness Handicap Inventory and dynamic balance measured with a seesaw platform moving either in the anterior-posterior or in the mediolateral direction. RESULTS:: The mean DHI score was 25.8 +/- 18.7 and the range was 0 to 68. Dizziness Handicap Inventory scores did not differ significantly between the different unilateral vestibular loss groups studied. No difference was detected between the groups for the 3 subscores (emotional, functional, and physical), except that the older-than-1-year group had a significantly higher physical score than the 2 others. No correlation was found between DHI scores and postural indicators for either direction of the platform. However, patients unable to maintain balance when the seesaw platform moved in the mediolateral direction had significantly higher DHI scores than those who did not fall. CONCLUSION:: Even if they are not directly related, we suggest that DHI and dynamic posturography are complementary approaches for appreciating the vestibular compensation process and are thus useful for postoperative counseling for vestibular loss patients. PMID- 17728691 TI - Diagnosis and management of intracochlear schwannomas. AB - OBJECTIVE: To describe and analyze a series of intracochlear schwannomas. METHODS: From 1987 to 2005, 19 patients with schwannomas involving the cochlea were included in this series. Clinical, audiovestibular, and imaging data concerning initial and follow-up visits were collected. RESULTS: The mean age was 54 years (range, 25-71 yr). The series comprised 10 women and 9 men, 18 solitary tumors and 1 neurofibromatosis Type 2 patient. The mean diagnosis delay was 11 years (range, 1-31 yr). At diagnosis, a total or profound hearing loss (Class D of American Academy of Otolaryngology-Head and Neck Surgery classification) was noted in 17 patients (89%), and a severe loss (Class C) was reported in 2 patients (11%). Facial paresis was reported in 2 patients (11%; Grades 2 and 4 of House and Brackmann classification). Magnetic resonance imaging showed an involvement of the posterior labyrinth in 8 patients (37%), an extension of the schwannoma to the internal auditory meatus in 8 patients (37%), and a cerebellopontine angle extension in 7 patients (32%). In 11 patients (58%), the schwannoma was removed through a transotic route. In the 8 remaining patients, a watch-and-rescan policy was decided. The postoperative course was uneventful. Postoperative follow-up period was 27 months (range, 6-88 mo). Postoperative facial function was assessed as Grade 1 in 7 patients, as Grade 2 in 4, and as Grade 4 in 1 patient. CONCLUSION: The diagnosis of intracochlear schwannomas can be difficult on magnetic resonance imaging. The diagnosis should be considered in all unilateral hearing losses. PMID- 17728692 TI - Salmonella serotype enteritidis infections among workers producing poultry vaccine--Maine, November-December 2006. AB - On November 15, 2006, the Maine Department of Health and Human Services (MDHHS) was notified of a case of salmonellosis (a nationally notifiable disease) in an employee of a facility that produced poultry vaccine. When a second case of salmonellosis in another employee at the same facility was reported on November 25, MDHHS began an outbreak investigation. Results of that investigation suggested that 21 employees of the facility became ill during a 1-month period from exposure to a strain of Salmonella serotype Enteritidis (SE) that was used in vaccine production. Infection was thought to have resulted from environmental contamination after the spill of a liquid containing a high concentration of SE. As a result, MDHHS recommended that the facility improve its infection-control procedures to better protect workers. This outbreak highlights occupational risks that can be associated with the manufacture of veterinary biologics involving human pathogens. PMID- 17728693 TI - National, state, and local area vaccination coverage among children aged 19-35 months--United States, 2006. AB - The National Immunization Survey (NIS) provides vaccination coverage estimates among children aged 19-35 months for each of the 50 states and selected urban and county areas. This report describes the findings of the 2006 NIS, which indicated increases in national coverage with pneumococcal conjugate vaccine (PCV) and varicella vaccine (VAR) and a stable coverage level for the 4:3:1:3:3:1 vaccine series (i.e., > or =4 doses of diphtheria, tetanus toxoid, and any acellular pertussis vaccine [DTaP]; > or =3 doses of poliovirus vaccine; > or =1 dose of measles, mumps, and rubella vaccine [MMR]; > or =3 doses of Haemophilus influenzae type b [Hib] vaccine; > or =3 doses of hepatitis B vaccine [HepB]; and > or =1 dose of VAR). However, national coverage estimates remained below the Healthy People 2010 target of 90% coverage for PCV, DTaP, and VAR and below the 80% target for the 4:3:1:3:3:1 vaccine series. No significant racial/ethnic disparities in 4:3:1:3:3:1 series coverage were observed after controlling for family income. State and local immunization programs should continue to identify and target children who are not fully vaccinated, especially because of low socioeconomic status and other barriers. PMID- 17728694 TI - National vaccination coverage among adolescents aged 13-17 years--United States, 2006. AB - Before 2005, vaccines were administered during adolescence to "catch up" children with vaccinations not received at a younger age, with the exception of the tetanus and diphtheria (Td) booster. However, since 2005, three new vaccines specifically for older children have been licensed and recommended in the United States: meningococcal conjugate vaccine (MCV4) for those aged 11-12 years and 15 years; tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine for those aged 11-12 years (or at ages 13-18 years if not received at ages 11-12 years); and human papillomavirus (HPV) vaccine for girls aged 11-12 years (or at ages 13-18 years if not received at 11-12 years). Since 1996, the Advisory Committee on Immunization Practices (ACIP) and professional organizations, including the American Academy of Pediatrics (AAP), the American Academy of Family Physicians (AAFP), and the American Medical Association (AMA), have recommended a health-care visit at ages 11-12 years for receipt of recommended vaccinations. In addition, a Healthy People 2010 objective (14-27) is to achieve > or =90% vaccination coverage among adolescents aged 13-15 years for certain vaccines. In 2006, for the first time, the National Immunization Survey (NIS) collected provider-reported vaccination information for adolescents aged 13 17 years (NIS-Teen). This report describes the results of that survey, which indicated that the Healthy People 2010 target has not been met for any of the vaccines analyzed. HPV vaccination coverage is not included in this report because NIS-Teen was conducted before HPV vaccination recommendations were published in March 2007. Routine health-care visits for adolescents should be encouraged, with emphasis on a visit at ages 11-12 years, and providers should continue to assess the need for vaccinations at every opportunity. NIS-Teen will be conducted annually to monitor coverage with recommended vaccines during ages 11-17 years and to identify groups with lower coverage. PMID- 17728696 TI - Synaptic plasticity: multiple forms, functions, and mechanisms. AB - Experiences, whether they be learning in a classroom, a stressful event, or ingestion of a psychoactive substance, impact the brain by modifying the activity and organization of specific neural circuitry. A major mechanism by which the neural activity generated by an experience modifies brain function is via modifications of synaptic transmission; that is, synaptic plasticity. Here, we review current understanding of the mechanisms of the major forms of synaptic plasticity at excitatory synapses in the mammalian brain. We also provide examples of the possible developmental and behavioral functions of synaptic plasticity and how maladaptive synaptic plasticity may contribute to neuropsychiatric disorders. PMID- 17728695 TI - The effect of high-dose enteral glutamine on the incidence and severity of mucositis in paediatric oncology patients. AB - BACKGROUND/OBJECTIVE: The study was conducted to determine if enteral glutamine, 0.65 g kg(-1) daily for 7 days, is effective in reducing the incidence and severity of mucositis in paediatric oncology patients when given alongside chemotherapy. The study was carried out at St James's University Hospital, Leeds, UK. SUBJECTS/METHODS: This was a randomized study using the patients as their own controls. Seventy-six patients undergoing treatment for paediatric malignancy having at least two identical courses of chemotherapy and at risk of developing mucositis participated in the study. Patients received one course of chemotherapy with glutamine and an identical course without. Alternate patients were allocated to have glutamine with course 1 or with course 2. The severity of symptoms of mucositis and the duration of enteral and parenteral nutrition were recorded. Daily ammonia levels were measured. RESULTS: Fifty patients completed the study. No statistical significance with regard to symptoms of mucositis was found. Fewer children receiving glutamine required parenteral nutrition (P=0.049), and the duration of parenteral nutrition was less (P=0.023). No adverse effects attributed to taking the glutamine were observed. CONCLUSIONS: The study showed that high-dose enteral glutamine did not reduce the incidence and severity of oral mucositis as determined by subjective toxicity measurements, but did show a significant reduction in parenteral nutrition usage. No adverse cumulative effect of this oral glutamine dose was observed. PMID- 17728697 TI - Association of RGS2 gene polymorphisms with suicide and increased RGS2 immunoreactivity in the postmortem brain of suicide victims. AB - Regulators of G-protein signaling are a family of proteins that negatively regulate the intracellular signaling of G protein-coupled receptors, such as the serotonin receptor. Recent studies have suggested that one of these proteins, the regulator of G-protein signaling 2 (RGS2), plays an important part in anxiety and/or aggressive behavior. To explore the involvement of the RGS2 gene in the vulnerability to suicide, we screened Japanese suicide victims for sequence variations in the RGS2 gene and carried out an association study of RGS2 gene polymorphisms with suicide victims. In the eight identified polymorphisms that were identified by mutation screening, we genotyped four common single-nucleotide polymorphisms (SNPs) in the RGS2 gene, and found significant differences in the distribution of the SNP3 (C+2971G, rs4606) genotypes and alleles of the SNP2 (C 395G, rs2746072) and the SNP3 between completed suicides and the controls. The distribution of the haplotype was also significantly different between the two groups (global p<0.0001). Furthermore, RGS2 immunoreactivity significantly increased in the amygdala and the prefrontal cortex (Brodmann area 9 (BA9)) of the postmortem brain of the suicide subjects. These findings suggest that RGS2 is genetically involved in the biological susceptibility to suicide in the Japanese population. PMID- 17728698 TI - Cannabinoid CB1 receptor antagonists attenuate cocaine's rewarding effects: experiments with self-administration and brain-stimulation reward in rats. AB - Previous studies suggest that cannabinoid CB1 receptors do not appear to be involved in cocaine's rewarding effects, as assessed by the use of SR141716A, a prototypic CB1 receptor antagonist and CB1-knockout mice. In the present study, we found that blockade of CB1 receptors by AM 251 (1-10 mg/kg), a novel CB1 receptor antagonist, dose-dependently lowered (by 30-70%) the break point for cocaine self-administration under a progressive-ratio (PR) reinforcement schedule in rats. The same doses of SR141716 (freebase form) maximally lowered the break point by 35%, which did not reach statistical significance. Neither AM 251 nor SR141716 altered cocaine self-administration under a fixed-ratio (FR2) reinforcement schedule. AM 251 (0.1-3 mg/kg) also significantly and dose dependently inhibited (by 25-90%) cocaine-enhanced brain stimulation reward (BSR), while SR141716 attenuated cocaine's BSR-enhancing effect only at 3 mg/kg (by 40%). When the dose was increased to 10 or 20 mg/kg, both AM 251 and SR141716 became less effective, with AM 251 only partially inhibiting cocaine-enhanced BSR and PR cocaine self-administration, and SR141716 having no effect. AM 251 alone, at all doses tested, had no effect on BSR, while high doses of SR141716 alone significantly inhibited BSR. These data suggest that blockade of CB1 receptors by relatively low doses of AM 251 dose-dependently inhibits cocaine's rewarding effects, whereas SR141716 is largely ineffective, as assessed by both PR cocaine self-administration and BSR. Thus, AM 251 or other more potent CB1 receptor antagonists deserve further study as potentially effective anti-cocaine medications. PMID- 17728699 TI - In vitro and in vivo characterization of the non-peptide NK3 receptor antagonist SB-223412 (talnetant): potential therapeutic utility in the treatment of schizophrenia. AB - Neurokinin-3 (NK3) receptors are concentrated in forebrain and basal ganglia structures within the mammalian CNS. This distribution, together with the modulatory influence of NK3 receptors on monoaminergic neurotransmission, has led to the hypothesis that NK3 receptor antagonists may have therapeutic efficacy in the treatment of psychiatric disorders. Here we describe the in vitro and in vivo characterization of the highly selective NK3 receptor antagonist talnetant (SB 223412). Talnetant has high affinity for recombinant human NK3 receptors (pKi 8.7) and demonstrates selectivity over other neurokinin receptors (pKi NK2 = 6.6 and NK1<4). In native tissue-binding studies, talnetant displayed high affinity for the guinea pig NK3 receptor (pKi 8.5). Functionally, talnetant competitively antagonized neurokinin B (NKB)-induced responses at the human recombinant receptor in both calcium and phosphoinositol second messenger assay systems (pA2 of 8.1 and 7.7, respectively). In guinea pig brain slices, talnetant antagonized NKB-induced increases in neuronal firing in the medial habenula (pKB = 7.9) and senktide-induced increases in neuronal firing in the substantia nigra pars compacta (pKB = 7.7) with no diminution of maximal agonist efficacy, suggesting competitive antagonism at native NK3 receptors. Talnetant (3-30 mg/kg i.p.) significantly attenuated senktide-induced 'wet dog shake' behaviors in the guinea pig in a dose-dependent manner. Microdialysis studies demonstrated that acute administration of talnetant (30 mg/kg i.p.) produced significant increases in extracellular dopamine and norepinephrine in the medial prefrontal cortex and attenuated haloperidol-induced increases in nucleus accumbens dopamine levels in the freely moving guinea pigs. Taken together, these data demonstrate that talnetant is a selective, competitive, brain-penetrant NK3 receptor antagonist with the ability to modulate mesolimbic and mesocortical dopaminergic neurotransmission and hence support its potential therapeutic utility in the treatment of schizophrenia. PMID- 17728700 TI - Neuroplasticity mediated by altered gene expression. AB - Plasticity in the brain is important for learning and memory, and allows us to respond to changes in the environment. Furthermore, long periods of stress can lead to structural and excitatory changes associated with anxiety and depression that can be reversed by pharmacological treatment. Drugs of abuse can also cause long-lasting changes in reward-related circuits, resulting in addiction. Each of these forms of long-term plasticity in the brain requires changes in gene expression. Upon stimulation, second messenger pathways are activated that lead to an enhancement in transcription factor activity at gene promoters. This stimulation results in the expression of new growth factors, ion channels, structural molecules, and other proteins necessary to alter the neuronal circuit. With repeated stimulation, more permanent modifications to transcription factors and chromatin structure are made that result in either sensitization or desensitization of a circuit. Studies are beginning to uncover the molecular mechanisms that lead to these types of long-term changes in the brain. This review summarizes some of the major transcriptional mechanisms that are thought to underlie neuronal and behavioral plasticity. PMID- 17728702 TI - Effects of long-term elevated glucose on collagen formation by mesangial cells. AB - Glomerulosclerosis is one of the complications of diabetes that occurs after many years of uncontrolled hyperglycemia. Mesangial cells (MCs) exposed to high glucose (HG) for short periods have shown that transforming growth factor-beta (TGF-beta) and activated diacylglycerol-dependent protein kinase C (PKC) mediate increased collagen formation. Our study examined collagen formation by MCs exposed to HG for 8 weeks. Exposure to HG in overnight culture resulted in the activation of all PKC isoforms. In contrast, 8-week exposure to HG resulted in the persistent activation of PKC-delta, did not change PKC-alpha or -beta activity, and decreased PKC-epsilon activity while increasing collagen I and IV gene and protein expression. Collagen IV accumulation was reversed by specific PKC-delta inhibition. Collagen IV gene expression was completely normalized by TGF-beta neutralization; however, this was associated with plasminogen activator inhibitor-1 (PAI-1) overexpression and a modest reduction in collagen protein. Our studies suggest that prolonged exposure to HG results in PKC-delta-driven collagen accumulation by MCs mediated by PAI-1 but independent of TGF-beta. PMID- 17728703 TI - Accumulation of free adduct glycation, oxidation, and nitration products follows acute loss of renal function. AB - Glycation, oxidation, and nitration of endogenous proteins occur spontaneously and these modifications are also present in foods. Increased levels of these chemical changes are associated with chronic renal failure; however, little is known about acute kidney failure. We measured these modifications of plasma protein and related free adducts in plasma following bilateral nephrectomy and bilateral ureteral obstruction. Advanced glycation end-product (AGE) residues of plasma protein were increased 3 h post-surgery, and thereafter slowly decreased in all groups, reflecting changes in plasma protein synthesis and transcapillary flow post-surgery. Ureteral ligation increased oxidation and nitration adduct residues. There were, however, marked increases in AGE, dityrosine, or 3 nitrotyrosine free adducts in both nephrectomized and ureter-ligated rats compared to rats that had undergone sham operations. There were lower modified adduct concentrations in the ureter-ligated compared to the nephrectomized rats, reflecting residual glomerular filtration and tubular removal. There was no increase in glycated, oxidized, and nitrated proteins. Glyoxal and methylglyoxal were also increased in both renal failure models. Our study shows that the acute loss of renal function and urinary excretion leads to the accumulation of AGE, oxidation, and nitration free adducts in the plasma. PMID- 17728701 TI - Contribution of cystine-glutamate antiporters to the psychotomimetic effects of phencyclidine. AB - Altered glutamate signaling contributes to a myriad of neural disorders, including schizophrenia. While synaptic levels are intensely studied, nonvesicular release mechanisms, including cystine-glutamate exchange, maintain high steady-state glutamate levels in the extrasynaptic space. The existence of extrasynaptic receptors, including metabotropic group II glutamate receptors (mGluR), pose nonvesicular release mechanisms as unrecognized targets capable of contributing to pathological glutamate signaling. We tested the hypothesis that activation of cystine-glutamate antiporters using the cysteine prodrug N acetylcysteine would blunt psychotomimetic effects in the rodent phencyclidine (PCP) model of schizophrenia. First, we demonstrate that PCP elevates extracellular glutamate in the prefrontal cortex, an effect that is blocked by N acetylcysteine pretreatment. To determine the relevance of the above finding, we assessed social interaction and found that N-acetylcysteine reverses social withdrawal produced by repeated PCP. In a separate paradigm, acute PCP resulted in working memory deficits assessed using a discrete trial t-maze task, and this effect was also reversed by N-acetylcysteine pretreatment. The capacity of N acetylcysteine to restore working memory was blocked by infusion of the cystine glutamate antiporter inhibitor (S)-4-carboxyphenylglycine into the prefrontal cortex or systemic administration of the group II mGluR antagonist LY341495 indicating that the effects of N-acetylcysteine requires cystine-glutamate exchange and group II mGluR activation. Finally, protein levels from postmortem tissue obtained from schizophrenic patients revealed significant changes in the level of xCT, the active subunit for cystine-glutamate exchange, in the dorsolateral prefrontal cortex. These data advance cystine-glutamate antiporters as novel targets capable of reversing the psychotomimetic effects of PCP. PMID- 17728704 TI - Glomerulotubular disconnection in neonatal mice after relief of partial ureteral obstruction. AB - Ureteropelvic junction obstruction is a common cause of congenital obstructive nephropathy. To study the pathogenesis of nephropathy, a variable-partial, complete or a sham unilateral ureteral obstruction (UUO) was produced in mice within 2 days of birth. The obstruction was released in some animals at 7 days and kidneys harvested at 7-42 days of age for histologic and morphometric study. Renal parenchymal growth was stunted by partial UUO with the impairment proportional to the duration and severity of obstruction. Proximal tubule apoptosis and glomerulotubular disconnection led to nephron loss. Relief of partial UUO arrested glomerulotubular disconnection, resolved tubule atrophy, and interstitial fibrosis with remodeling of the renal architecture. Relief of severe UUO did not result in recovery. Compensatory growth of the contralateral kidney depended on the severity of obstruction. Our studies indicate that relief of moderate UUO will minimize nephron loss. Application of this technique to mutant mice will help develop future therapies to enhance nephron recovery. PMID- 17728705 TI - HDL-inflammatory index correlates with poor outcome in hemodialysis patients. AB - Oxidative stress and cardiovascular disease are risk factor of patients with chronic kidney disease (CKD) on maintenance hemodialysis. We used the fluorescence of low-density lipoprotein as an index of its proinflammatory potential to examine any role that high-density lipoprotein (HDL) might have in promoting this effect. The total body fat of the patients was measured by means of near-infrared interactance and their quality of life by means of SF36 questionnaires. In 189 randomly selected patients, followed for 30 months, HDL was found to be significantly anti-inflammatory but with a large standard deviation. Fully 17% of the patients had a decidedly proinflammatory index along with inferior SF36 scores. The patients were divided into 10% increments of total body fat percentages up to 40%. HDL was found to be progressively proinflammatory the higher the body fat content. Patients with a higher HDL proinflammatory index had a higher 30-month adjusted hazard ratio for death than those whose HDL were seen to be anti-inflammatory. Our findings suggest an important role of inflammatory HDL in patients with CKD leading to poor outcome. PMID- 17728706 TI - Deficiency of heme oxygenase-1 impairs renal hemodynamics and exaggerates systemic inflammatory responses to renal ischemia. AB - Heme oxygenase-1 may exert cytoprotective effects. In this study we examined the sensitivity of heme oxygenase-1 knockout (HO-1(-/-)) mice to renal ischemia by assessing glomerular filtration rate (GFR) and cytokine expression in the kidney, and inflammatory responses in the systemic circulation and in vital extrarenal organs. Four hours after renal ischemia, the GFR of HO-1(-/-) mice was much lower than that of wild-type mice in the absence of changes in renal blood flow or cardiac output. Eight hours after renal ischemia, there was a marked induction of interleukin-6 (IL-6) mRNA and its downstream signaling effector, phosphorylated signal transducer and activator of transcription 3 (pSTAT3), in the kidney, lung, and heart in HO-1(-/-) mice. Systemic levels of IL-6 were markedly and uniquely increased in HO-1(-/-) mice after ischemia as compared to wild-type mice. The administration of an antibody to IL-6 protected against the renal dysfunction and mortality observed in HO-1(-/-) mice following ischemia. We suggest that the exaggerated production of IL-6, occurring regionally and systemically following localized renal ischemia, in an HO-1-deficient state may underlie the heightened sensitivity observed in this setting. PMID- 17728708 TI - Uremia impairs monocyte and monocyte-derived dendritic cell function in hemodialysis patients. AB - Patients with chronic renal failure maintained on intermittent hemodialysis have frequent infections and a suboptimal response to vaccinations. Dendritic cells are potent antigen-presenting cells essential for the initiation and maintenance of innate and adaptive immunity. In this study we used uremic sera from hemodialysis patients to measure its impact on monocyte and monocyte-derived dendritic cell function in vitro. Monocytes from healthy and uremic subjects were isolated using immunomagnetic beads and differentiated into dendritic cells in the presence of either complete sera or sera from hemodialysis patients. Dendritic cells from normal patients cultured in uremic sera had decreased endocytosis and impaired maturation. These cells, however, had enhanced IL-12p70 production and increased allogeneic T-cell proliferation compared to cells of normal subjects cultured in normal sera. Monocyte derived dendritic cells of hemodialysis patients cultured in either normal or uremic sera were functionally impaired for endocytosis and maturation but had enhanced IL-12p70 production and allogeneic T-cell proliferation only when cultured with uremic sera. High concentrations of urea in normal sera inhibited all aspects of normal dendritic cell function in vitro. Our study suggests that hemodialysis regimes tailored to remove uremic toxins more efficiently may improve immune functions of these patients. PMID- 17728707 TI - Effects of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients. AB - Elevated serum phosphorus and calcium are associated with arterial calcification and mortality in dialysis patients. Unlike calcium-based binders, sevelamer attenuates arterial calcification but it is unknown whether sevelamer affects mortality or morbidity. In a multicenter, randomized, open-label, parallel design trial we compared sevelamer and calcium-based binders on all-cause and cause specific mortality (cardiovascular, infection, and other) in prevalent hemodialysis patients. A total of 2103 patients were initially randomized to treatment and 1068 patients completed the study. All-cause mortality rates and cause-specific mortality rates were not significantly different. There was a significant age interaction on the treatment effect. Only in patients over 65 years of age was there a significant effect of sevelamer in lowering the mortality rate. There was a suggestion that sevelamer was associated with lower overall, but not cardiovascular-linked, mortality in older patients. We suggest that further research is needed to confirm these findings. PMID- 17728709 TI - Interleukin 2 for patients with renal cancer. PMID- 17728710 TI - Origins of breast cancer subtypes and therapeutic implications. AB - This Review summarizes and evaluates the current evidence for the cellular origins of breast cancer subtypes identified by different approaches such as histology, molecular pathology, genetic and gene-expression analysis. Emerging knowledge of the normal breast cell types has led to the hypothesis that the subtypes of breast cancer might arise from mutations or genetic rearrangements occurring in different populations of stem cells and progenitor cells. We describe the common distinguishing features of these breast cancer subtypes and explain how these features relate both to prognosis and to selection of the most appropriate therapy. Recent data indicate that breast tumors may originate from cancer stem cells. Consequently, inhibition of stem-cell self-renewal pathways should be explored because of the likelihood that residual stem cells might be resistant to current therapies. PMID- 17728711 TI - Surgery insight: surgical management of pancreatic cancer. AB - Pancreatic ductal adenocarcinoma is a common malignancy of the gastrointestinal tract. The number of new cases diagnosed and the number of deaths each year are almost identical, demonstrating the particularly dismal prognosis for patients affected by this disease. Despite recent advances in the field of medical and radiation oncology, and the introduction of neoadjuvant and adjuvant regimens, surgery remains the single most important modality for the treatment of pancreatic ductal adenocarcinoma. Surgery for pancreatic cancer is widely viewed as a complex procedure associated with considerable perioperative morbidity and mortality. Many aspects of surgery for pancreatic cancer, such as the extent of resection, the value of vascular resection, the use of laparoscopy, and the importance of treatment at high-volume centers, are currently under debate. This Review describes the current status of surgical treatment for pancreatic ductal adenocarcinoma, and highlights the new developments in this field. PMID- 17728712 TI - Mechanisms of disease: angiogenesis and the management of breast cancer. AB - Demonstration of the clinically significant activity of bevacizumab in breast cancer has attracted a great deal of interest. Numerous other antiangiogenic treatments are in clinical development and some established therapies including tamoxifen and trastuzumab might function, in part, by suppressing angiogenesis. In this Review, we discuss the potential of various components of the angiogenic pathway as prognostic and predictive factors in breast cancer. In addition, we describe existing clinical trials of antiangiogenic agents and the challenges facing the clinical development and optimum use of these agents for the treatment of breast cancer. PMID- 17728713 TI - Does small-cell phenotype predict the natural history of prostate cancer? A case study in disease behavior. AB - BACKGROUND: A 52-year-old man presented to his urologist with hematuria and symptoms of frequency and incomplete voiding. The patient received antibiotics without symptom resolution. His prostate-specific antigen (PSA) level was 6.6 ng/ml and digital rectal examination revealed a normal-sized firm prostate gland. Biopsy obtained by transurethral resection revealed poorly differentiated Gleason 9 adenocarcinoma of the prostate with small-cell/neuroendocrine features. Pure small-cell cancer or poorly differentiated prostate cancer may secrete little or no PSA. One should be alerted to this phenotype in a patient with large volume disease on biopsy or examination and a low PSA or PSA not in proportion to tumor burden. INVESTIGATIONS: Digital rectal examination, laboratory tests, cystoscopy, prostatic chips obtained from transurethral resection, prostate biopsy, bone scan, CT scan of the chest, abdomen and pelvis. DIAGNOSIS: Poorly differentiated Gleason 9 adenocarcinoma of the prostate with small-cell/neuroendocrine features. MANAGEMENT: Transurethral resection, androgen blockade with a gonadotropin releasing hormone analog and antiandrogen flutamide, oral bicalutamide, docetaxel and oral estramustine. Total pelvic exenteration with ileal conduit urinary diversion and permanent end-colostomy formation, percutaneous nephrostomy placement, cisplatin combined with etoposide. PMID- 17728714 TI - Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU. AB - Stem cells are proposed to segregate chromosomes asymmetrically during self renewing divisions so that older ('immortal') DNA strands are retained in daughter stem cells whereas newly synthesized strands segregate to differentiating cells. Stem cells are also proposed to retain DNA labels, such as 5-bromo-2-deoxyuridine (BrdU), either because they segregate chromosomes asymmetrically or because they divide slowly. However, the purity of stem cells among BrdU-label-retaining cells has not been documented in any tissue, and the 'immortal strand hypothesis' has not been tested in a system with definitive stem cell markers. Here we tested these hypotheses in haematopoietic stem cells (HSCs), which can be highly purified using well characterized markers. We administered BrdU to newborn mice, mice treated with cyclophosphamide and granulocyte colony-stimulating factor, and normal adult mice for 4 to 10 days, followed by 70 days without BrdU. In each case, less than 6% of HSCs retained BrdU and less than 0.5% of all BrdU-retaining haematopoietic cells were HSCs, revealing that BrdU has poor specificity and poor sensitivity as an HSC marker. Sequential administration of 5-chloro-2-deoxyuridine and 5-iodo-2-deoxyuridine indicated that all HSCs segregate their chromosomes randomly. Division of individual HSCs in culture revealed no asymmetric segregation of the label. Thus, HSCs cannot be identified on the basis of BrdU-label retention and do not retain older DNA strands during division, indicating that these are not general properties of stem cells. PMID- 17728715 TI - MicroRNA control of Nodal signalling. AB - MicroRNAs are crucial modulators of gene expression, yet their involvement as effectors of growth factor signalling is largely unknown. Ligands of the transforming growth factor-beta superfamily are essential for development and adult tissue homeostasis. In early Xenopus embryos, signalling by the transforming growth factor-beta ligand Nodal is crucial for the dorsal induction of the Spemann's organizer. Here we report that Xenopus laevis microRNAs miR-15 and miR-16 restrict the size of the organizer by targeting the Nodal type II receptor Acvr2a. Endogenous miR-15 and miR-16 are ventrally enriched as they are negatively regulated by the dorsal Wnt/beta-catenin pathway. These findings exemplify the relevance of microRNAs as regulators of early embryonic patterning acting at the crossroads of fundamental signalling cascades. PMID- 17728720 TI - More than lip service. PMID- 17728716 TI - Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. AB - A subset of neurons in the brain, known as 'glucose-excited' neurons, depolarize and increase their firing rate in response to increases in extracellular glucose. Similar to insulin secretion by pancreatic beta-cells, glucose excitation of neurons is driven by ATP-mediated closure of ATP-sensitive potassium (K(ATP)) channels. Although beta-cell-like glucose sensing in neurons is well established, its physiological relevance and contribution to disease states such as type 2 diabetes remain unknown. To address these issues, we disrupted glucose sensing in glucose-excited pro-opiomelanocortin (POMC) neurons via transgenic expression of a mutant Kir6.2 subunit (encoded by the Kcnj11 gene) that prevents ATP-mediated closure of K(ATP) channels. Here we show that this genetic manipulation impaired the whole-body response to a systemic glucose load, demonstrating a role for glucose sensing by POMC neurons in the overall physiological control of blood glucose. We also found that glucose sensing by POMC neurons became defective in obese mice on a high-fat diet, suggesting that loss of glucose sensing by neurons has a role in the development of type 2 diabetes. The mechanism for obesity induced loss of glucose sensing in POMC neurons involves uncoupling protein 2 (UCP2), a mitochondrial protein that impairs glucose-stimulated ATP production. UCP2 negatively regulates glucose sensing in POMC neurons. We found that genetic deletion of Ucp2 prevents obesity-induced loss of glucose sensing, and that acute pharmacological inhibition of UCP2 reverses loss of glucose sensing. We conclude that obesity-induced, UCP2-mediated loss of glucose sensing in glucose-excited neurons might have a pathogenic role in the development of type 2 diabetes. PMID- 17728721 TI - Pulling rank. PMID- 17728722 TI - Space for capitalism. PMID- 17728725 TI - Market takes a gamble on carbon futures. PMID- 17728726 TI - Air force had early warning of pulsars. PMID- 17728727 TI - Cheaper approaches to flu divide researchers. PMID- 17728729 TI - Flying insects threaten to deafen Japan. PMID- 17728730 TI - Space, science and the bottom line. Alan Stern interviewed by Alexandra Witze. PMID- 17728731 TI - No confidence vote for agency head. PMID- 17728733 TI - How to make it in Moscow. PMID- 17728734 TI - Physics in the cell: spring theory. PMID- 17728735 TI - Space: dreams of the new space race. PMID- 17728736 TI - Climate: Sawyer predicted rate of warming in 1972. PMID- 17728737 TI - Fires and climate linked in nineteenth century. PMID- 17728738 TI - Libya should stop denying scientific evidence on HIV. PMID- 17728739 TI - Cashing in palm oil for conservation. PMID- 17728745 TI - Theoretical physics: a black hole full of answers. PMID- 17728747 TI - Planets: the first movement. PMID- 17728746 TI - Molecular biology: damage control. PMID- 17728748 TI - Translation: duality in the genetic code. PMID- 17728749 TI - Palaeoclimate: oxygen's rise reduced. PMID- 17728750 TI - Materials science: polymer crystals downsized. PMID- 17728751 TI - Rapid planetesimal formation in turbulent circumstellar disks. AB - During the initial stages of planet formation in circumstellar gas disks, dust grains collide and build up larger and larger bodies. How this process continues from metre-sized boulders to kilometre-scale planetesimals is a major unsolved problem: boulders are expected to stick together poorly, and to spiral into the protostar in a few hundred orbits owing to a 'headwind' from the slower rotating gas. Gravitational collapse of the solid component has been suggested to overcome this barrier. But even low levels of turbulence will inhibit sedimentation of solids to a sufficiently dense midplane layer, and turbulence must be present to explain observed gas accretion in protostellar disks. Here we report that boulders can undergo efficient gravitational collapse in locally overdense regions in the midplane of the disk. The boulders concentrate initially in transient high pressure regions in the turbulent gas, and these concentrations are augmented a further order of magnitude by a streaming instability driven by the relative flow of gas and solids. We find that gravitationally bound clusters form with masses comparable to dwarf planets and containing a distribution of boulder sizes. Gravitational collapse happens much faster than radial drift, offering a possible path to planetesimal formation in accreting circumstellar disks. PMID- 17728752 TI - The development of a protoplanetary disk from its natal envelope. AB - Class 0 protostars, the youngest type of young stellar objects, show many signs of rapid development from their initial, spheroidal configurations, and therefore are studied intensively for details of the formation of protoplanetary disks within protostellar envelopes. At millimetre wavelengths, kinematic signatures of collapse have been observed in several such protostars, through observations of molecular lines that probe their outer envelopes. It has been suggested that one or more components of the proto-multiple system NGC 1333-IRAS 4 (refs 1, 2) may display signs of an embedded region that is warmer and denser than the bulk of the envelope. Here we report observations that reveal details of the core on Solar System dimensions. We detect in NGC 1333-IRAS 4B a rich emission spectrum of H2O, at wavelengths 20-37 microm, which indicates an origin in extremely dense, warm gas. We can model the emission as infall from a protostellar envelope onto the surface of a deeply embedded, dense disk, and therefore see the development of a protoplanetary disk. This is the only example of mid-infrared water emission from a sample of 30 class 0 objects, perhaps arising from a favourable orientation; alternatively, this may be an early and short-lived stage in the evolution of a protoplanetary disk. PMID- 17728753 TI - Direct observation of second-order atom tunnelling. AB - Tunnelling of material particles through a classically impenetrable barrier constitutes one of the hallmark effects of quantum physics. When interactions between the particles compete with their mobility through a tunnel junction, intriguing dynamical behaviour can arise because the particles do not tunnel independently. In single-electron or Bloch transistors, for example, the tunnelling of an electron or Cooper pair can be enabled or suppressed by the presence of a second charge carrier due to Coulomb blockade. Here we report direct, time-resolved observations of the correlated tunnelling of two interacting ultracold atoms through a barrier in a double-well potential. For the regime in which the interactions between the atoms are weak and tunnel coupling dominates, individual atoms can tunnel independently, similar to the case of a normal Josephson junction. However, when strong repulsive interactions are present, two atoms located on one side of the barrier cannot separate, but are observed to tunnel together as a pair in a second-order co-tunnelling process. By recording both the atom position and phase coherence over time, we fully characterize the tunnelling process for a single atom as well as the correlated dynamics of a pair of atoms for weak and strong interactions. In addition, we identify a conditional tunnelling regime in which a single atom can only tunnel in the presence of a second particle, acting as a single atom switch. Such second order tunnelling events, which are the dominating dynamical effect in the strongly interacting regime, have not been previously observed with ultracold atoms. Similar second-order processes form the basis of superexchange interactions between atoms on neighbouring lattice sites of a periodic potential, a central component of proposals for realizing quantum magnetism. PMID- 17728754 TI - Increased subaerial volcanism and the rise of atmospheric oxygen 2.5 billion years ago. AB - The hypothesis that the establishment of a permanently oxygenated atmosphere at the Archaean-Proterozoic transition (approximately 2.5 billion years ago) occurred when oxygen-producing cyanobacteria evolved is contradicted by biomarker evidence for their presence in rocks 200 million years older. To sustain vanishingly low oxygen levels despite near-modern rates of oxygen production from approximately 2.7-2.5 billion years ago thus requires that oxygen sinks must have been much larger than they are now. Here we propose that the rise of atmospheric oxygen occurred because the predominant sink for oxygen in the Archaean era enhanced submarine volcanism-was abruptly and permanently diminished during the Archaean-Proterozoic transition. Observations are consistent with the corollary that subaerial volcanism only became widespread after a major tectonic episode of continental stabilization at the beginning of the Proterozoic. Submarine volcanoes are more reducing than subaerial volcanoes, so a shift from predominantly submarine to a mix of subaerial and submarine volcanism more similar to that observed today would have reduced the overall sink for oxygen and led to the rise of atmospheric oxygen. PMID- 17728755 TI - Projected increase in continental runoff due to plant responses to increasing carbon dioxide. AB - In addition to influencing climatic conditions directly through radiative forcing, increasing carbon dioxide concentration influences the climate system through its effects on plant physiology. Plant stomata generally open less widely under increased carbon dioxide concentration, which reduces transpiration and thus leaves more water at the land surface. This driver of change in the climate system, which we term 'physiological forcing', has been detected in observational records of increasing average continental runoff over the twentieth century. Here we use an ensemble of experiments with a global climate model that includes a vegetation component to assess the contribution of physiological forcing to future changes in continental runoff, in the context of uncertainties in future precipitation. We find that the physiological effect of doubled carbon dioxide concentrations on plant transpiration increases simulated global mean runoff by 6 per cent relative to pre-industrial levels; an increase that is comparable to that simulated in response to radiatively forced climate change (11 +/- 6 per cent). Assessments of the effect of increasing carbon dioxide concentrations on the hydrological cycle that only consider radiative forcing will therefore tend to underestimate future increases in runoff and overestimate decreases. This suggests that freshwater resources may be less limited than previously assumed under scenarios of future global warming, although there is still an increased risk of drought. Moreover, our results highlight that the practice of assessing the climate-forcing potential of all greenhouse gases in terms of their radiative forcing potential relative to carbon dioxide does not accurately reflect the relative effects of different greenhouse gases on freshwater resources. PMID- 17728756 TI - Dating the origin of the Orchidaceae from a fossil orchid with its pollinator. AB - Since the time of Darwin, evolutionary biologists have been fascinated by the spectacular adaptations to insect pollination exhibited by orchids. However, despite being the most diverse plant family on Earth, the Orchidaceae lack a definitive fossil record and thus many aspects of their evolutionary history remain obscure. Here we report an exquisitely preserved orchid pollinarium (of Meliorchis caribea gen. et sp. nov.) attached to the mesoscutellum of an extinct stingless bee, Proplebeia dominicana, recovered from Miocene amber in the Dominican Republic, that is 15-20 million years (Myr) old. This discovery constitutes both the first unambiguous fossil of Orchidaceae and an unprecedented direct fossil observation of a plant-pollinator interaction. By applying cladistic methods to a morphological character matrix, we resolve the phylogenetic position of M. caribea within the extant subtribe Goodyerinae (subfamily Orchidoideae). We use the ages of other fossil monocots and M. caribea to calibrate a molecular phylogenetic tree of the Orchidaceae. Our results indicate that the most recent common ancestor of extant orchids lived in the Late Cretaceous (76-84 Myr ago), and also suggest that the dramatic radiation of orchids began shortly after the mass extinctions at the K/T boundary. These results further support the hypothesis of an ancient origin for Orchidaceae. PMID- 17728757 TI - Mobility promotes and jeopardizes biodiversity in rock-paper-scissors games. AB - Biodiversity is essential to the viability of ecological systems. Species diversity in ecosystems is promoted by cyclic, non-hierarchical interactions among competing populations. Central features of such non-transitive relations are represented by the 'rock-paper-scissors' game, in which rock crushes scissors, scissors cut paper, and paper wraps rock. In combination with spatial dispersal of static populations, this type of competition results in the stable coexistence of all species and the long-term maintenance of biodiversity. However, population mobility is a central feature of real ecosystems: animals migrate, bacteria run and tumble. Here, we observe a critical influence of mobility on species diversity. When mobility exceeds a certain value, biodiversity is jeopardized and lost. In contrast, below this critical threshold all subpopulations coexist and an entanglement of travelling spiral waves forms in the course of time. We establish that this phenomenon is robust; it does not depend on the details of cyclic competition or spatial environment. These findings have important implications for maintenance and temporal development of ecological systems and are relevant for the formation and propagation of patterns in microbial populations or excitable media. PMID- 17728758 TI - The detection of carbonation by the Drosophila gustatory system. AB - There are five known taste modalities in humans: sweet, bitter, sour, salty and umami (the taste of monosodium glutamate). Although the fruitfly Drosophila melanogaster tastes sugars, salts and noxious chemicals, the nature and number of taste modalities in this organism is not clear. Previous studies have identified one taste cell population marked by the gustatory receptor gene Gr5a that detects sugars, and a second population marked by Gr66a that detects bitter compounds. Here we identify a novel taste modality in this insect: the taste of carbonated water. We use a combination of anatomical, calcium imaging and behavioural approaches to identify a population of taste neurons that detects CO2 and mediates taste acceptance behaviour. The taste of carbonation may allow Drosophila to detect and obtain nutrients from growing microorganisms. Whereas CO2 detection by the olfactory system mediates avoidance, CO2 detection by the gustatory system mediates acceptance behaviour, demonstrating that the context of CO2 determines appropriate behaviour. This work opens up the possibility that the taste of carbonation may also exist in other organisms. PMID- 17728759 TI - Tip60 is a haplo-insufficient tumour suppressor required for an oncogene-induced DNA damage response. AB - The acetyl-transferase Tip60 might influence tumorigenesis in multiple ways. First, Tip60 is a co-regulator of transcription factors that either promote or suppress tumorigenesis, such as Myc and p53. Second, Tip60 modulates DNA-damage response (DDR) signalling, and a DDR triggered by oncogenes can counteract tumour progression. Using E(mu)-myc transgenic mice that are heterozygous for a Tip60 gene (Htatip) knockout allele (hereafter denoted as Tip60+/- mice), we show that Tip60 counteracts Myc-induced lymphomagenesis in a haplo-insufficient manner and in a time window that is restricted to a pre- or early-tumoral stage. Tip60 heterozygosity severely impaired the Myc-induced DDR but caused no general DDR defect in B cells. Myc- and p53-dependent transcription were not affected, and neither were Myc-induced proliferation, activation of the ARF-p53 tumour suppressor pathway or the resulting apoptotic response. We found that the human TIP60 gene (HTATIP) is a frequent target for mono-allelic loss in human lymphomas and head-and-neck and mammary carcinomas, with concomitant reduction in mRNA levels. Immunohistochemical analysis also demonstrated loss of nuclear TIP60 staining in mammary carcinomas. These events correlated with disease grade and frequently concurred with mutation of p53. Thus, in both mouse and human, Tip60 has a haplo-insufficient tumour suppressor activity that is independent from-but not contradictory with-its role within the ARF-p53 pathway. We suggest that this is because critical levels of Tip60 are required for mounting an oncogene-induced DDR in incipient tumour cells, the failure of which might synergize with p53 mutation towards tumour progression. PMID- 17728764 TI - Polymorphisms in adenosine receptor genes are associated with infarct size in patients with ischemic cardiomyopathy. AB - The goal of this experiment was to identify the presence of genetic variants in the adenosine receptor genes and assess their relationship to infarct size in a population of patients with ischemic cardiomyopathy. Adenosine receptors play an important role in protecting the heart during ischemia and in mediating the effects of ischemic preconditioning. We sequenced DNA samples from 273 individuals with ischemic cardiomyopathy and from 203 normal controls to identify the presence of genetic variants in the adenosine receptor genes. Subsequently, we analyzed the relationship between the identified genetic variants and infarct size, left ventricular size, and left ventricular function. Three variants in the 3'-untranslated region of the A(1)-adenosine gene (nt 1689 C/A, nt 2206 Tdel, nt 2683del36) and an informative polymorphism in the coding region of the A3 adenosine gene (nt 1509 A/C I248L) were associated with changes in infarct size. These results suggest that genetic variants in the adenosine receptor genes may predict the heart's response to ischemia or injury and might also influence an individual's response to adenosine therapy. PMID- 17728765 TI - Rapamycin: something old, something new, sometimes borrowed and now renewed. AB - The molecular target of rapamycin (mTOR) is central to a complex intracellular signaling pathway and is involved in diverse processes including cell growth and proliferation, angiogenesis, autophagy, and metabolism. Although sirolimus (rapamycin), the oldest inhibitor of mTOR, was discovered more than 30 years ago, renewed interest in this pathway is evident by the numerous rapalogs recently developed. These newer agents borrow from the structure of sirolimus and, although there are some pharmacokinetic differences, they appear to differ little in terms of pharmacodynamic effects and overall tolerability. Given the multitude of potential applications for this class of agents and the decrease in cost that can be expected upon the expiration of sirolimus patents, renewed focus on this agent is warranted. PMID- 17728766 TI - America competes--for now. PMID- 17728769 TI - New models of collaboration in genome-wide association studies: the Genetic Association Information Network. AB - The Genetic Association Information Network (GAIN) is a public-private partnership established to investigate the genetic basis of common diseases through a series of collaborative genome-wide association studies. GAIN has used new approaches for project selection, data deposition and distribution, collaborative analysis, publication and protection from premature intellectual property claims. These demonstrate a new commitment to shared scientific knowledge that should facilitate rapid advances in understanding the genetics of complex diseases. PMID- 17728770 TI - IL-7Ralpha and multiple sclerosis risk. PMID- 17728771 TI - A haplotype map for the laboratory mouse. PMID- 17728772 TI - An Arabidopsis haplotype map takes root. PMID- 17728773 TI - Cancer drugs to treat birth defects. PMID- 17728780 TI - MassARRAY assay: a more accurate method for JAK2V617F mutation detection in Chinese patients with myeloproliferative disorders. PMID- 17728781 TI - Multiple forms of nuclear p53 formed in human Raji and MEC1 cells treated with fludarabine. PMID- 17728782 TI - Genetically identical twin transplantation for chronic lymphocytic leukemia. AB - We identified 19 persons with B-cell chronic lymphocytic leukemia (CLL) who received genetically identical twin blood cell or bone marrow transplants after high-dose conditioning. Ten are alive (eight disease-free) with a median follow up of 89 months (range, 31-171 months); 5-year relapse rate was 50% (95% confidence interval (CI), 26-73%). Estimated 5-year survival and disease-free survival were 61% (95% CI, 37-82%) and 45% (95% CI, 23-68%). In two of four patients tested at 12 and 21 months by polymerase chain reaction no evidence of residual CLL was detected post-transplant. In one recipient who relapsed at 6 years, molecular studies showed a different CLL clone from that detected pretransplant. This clone was subsequently identified in the donor suggesting transfer of occult leukemia at the time of transplant. Genetically identical twin transplants can result in long-term disease-free survival and molecular remissions, these data suggest the potential for CLL control in the absence of allogeneic graft-versus-leukemia effect. The case of leukemia transfer indicates the need for careful evaluation of donors prior to graft collection. PMID- 17728783 TI - Deregulation of the Wilms' tumour gene 1 protein (WT1) by BCR/ABL1 mediates resistance to imatinib in human leukaemia cells. AB - The Wilms' tumour gene 1 (WT1) protein is highly expressed in most leukaemias. Co expression of WT1 and the fusion protein AML1-ETO in mice rapidly induces acute myeloid leukaemia (AML). Mechanisms behind expression of WT1, as well as consequences thereof, are still unclear. Here, we report that the fusion protein BCR/ABL1 increases expression of WT1 mRNA and protein via the phosphatidylinositol-3 kinase (PI3K)-Akt pathway. Inhibition of BCR/ABL1 or PI3K activity strongly suppressed transcription from WT1 promoter/enhancer reporters. Forced expression of BCR/ABL1 in normal human progenitor CD34+ cells increased WT1 mRNA and protein, further supporting the notion of BCR/ABL1-driven expression of WT1 in human haematopoietic cells. Forced expression of WT1 in K562 cells provided protection against cytotoxic effects of the ABL1 tyrosine kinase inhibitor imatinib, as judged by effects on viability measured by trypan blue exclusion, metabolic activity, annexin V and DAPI (4', 6-diamidino-2 phenylindole) staining. None of the isoforms provided any detectable protection against apoptosis induced by arsenic trioxide and only very weak protection against etoposide, indicating that WT1 interferes with specific apoptotic signalling pathways. Our data demonstrate that WT1 expression is induced by oncogenic signalling from BCR/ABL1 and that WT1 contributes to resistance against apoptosis induced by imatinib. PMID- 17728784 TI - Chromosomal localization of DNA methylation in small B-cell lymphoma. PMID- 17728785 TI - Further delineation of chromosomal consensus regions in primary mediastinal B cell lymphomas: an analysis of 37 tumor samples using high-resolution genomic profiling (array-CGH). AB - Primary mediastinal B-cell lymphoma (PMBL) is an aggressive extranodal B-cell non Hodgkin's lymphoma with specific clinical, histopathological and genomic features. To characterize further the genotype of PMBL, we analyzed 37 tumor samples and PMBL cell lines Med-B1 and Karpas1106P using array-based comparative genomic hybridization (matrix- or array-CGH) to a 2.8k genomic microarray. Due to a higher genomic resolution, we identified altered chromosomal regions in much higher frequencies compared with standard CGH: for example, +9p24 (68%), +2p15 (51%), +7q22 (32%), +9q34 (32%), +11q23 (18%), +12q (30%) and +18q21 (24%). Moreover, previously unknown small interstitial chromosomal low copy number alterations (for example, -6p21, -11q13.3) and a total of 19 DNA amplifications were identified by array-CGH. For 17 chromosomal localizations (10 gains and 7 losses), which were altered in more than 10% of the analyzed cases, we delineated minimal consensus regions based on genomic base pair positions. These regions and selected immunohistochemistries point to candidate genes that are discussed in the context of NF-kappaB transcription activation, human leukocyte antigen class I/II defects, impaired apoptosis and Janus kinase/signal transducer and activator of transcription (JAK/STAT) activation. Our data confirm the genomic uniqueness of this tumor and provide physically mapped genomic regions of interest for focused candidate gene analysis. PMID- 17728786 TI - Vorinostat and bortezomib significantly inhibit WT1 gene expression in MO7-e and P39 cell lines. PMID- 17728787 TI - Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a consensus statement from the International Working Group for Myelofibrosis Research and Treatment. PMID- 17728788 TI - Macrophage migration inhibitory factor (MIF) gene polymorphisms are associated with increased prostate cancer incidence. AB - Recurrent or persistent inflammation has emerged as an important factor in cancer development. Overexpression of macrophage migration inhibitory factor (MIF), an upstream regulator of innate immunity with pleiotropic effects on cell proliferation, has been implicated in prostate cancer (CaP). Two polymorphisms in the promoter of the MIF gene (-173G to C transition and seven copies of the -794 CATT repeat) are associated with increased MIF expression in vivo and poor prognosis in autoimmune diseases. We conducted a retrospective analysis of 131 CaP patients and 128 controls from a group of Veterans' Administration patients undergoing routine prostate-specific antigen screening. Patients with CaP were enrolled regardless of treatment. Inclusion criteria for the control group were absence of documented diagnosis of cancer and/or chronic inflammation within patient computerized records. Logistic regression demonstrated a significant association between CaP and the -173G/C, the -173C/C and the -794 7-CATT MIF polymorphisms (P<0.001). Patients with the -794 7-CATT allele had an increased risk of CaP recurrence at 5 years. Individuals with -173G/C, -173C/C and -794 7 CATT MIF genotypes have an increased incidence of CaP and these genotypes may serve as an independent marker for cancer recurrence. PMID- 17728789 TI - Sle3 and Sle5 can independently couple with Sle1 to mediate severe lupus nephritis. AB - Genetic analyses of the lupus-prone NZM2410 mouse have identified multiple susceptibility loci on chromosome 7, termed Sle3 and Sle5. Both of these loci were contained within a large congenic interval, originally termed as Sle3 that strongly impacts a variety of myeloid and T-cell phenotypes and mediates fatal lupus nephritis when combined with Sle1. We have now produced two subcongenic strains, B6.Sle3 and B6.Sle5, carrying the Sle3 and Sle5 intervals separately and characterized their phenotypes as monocongenic strains and individually in combination with Sle1. Neither B6.Sle3 nor B6.Sle5 monocongenic strain develop severe autoimmunity; however, both of these intervals cause the development of severe glomerulonephritis when combined with Sle1. Thus, B6.Sle1Sle3 and B6.Sle1Sle5 exhibit splenomegaly, expansion of activated B and CD4+ T-cell populations and high levels of IgG and IgM autoantibodies targeting multiple nuclear antigens, intact glomeruli and various other autoantigens. In addition, B6.Sle1Sle3 mice also produced higher levels of IgA antinuclear autoantibodies, which were implicated in the development of IgA nephropathy. Our results indicate that Sle3 and Sle5 can independently complement with Sle1, through shared and unique mechanisms, to mediate the development of severe autoimmunity. PMID- 17728791 TI - Monocytosis in BXSB mice is due to epistasis between Yaa and the telomeric region of chromosome 1 but does not drive the disease process. AB - The BXSB murine model of systemic lupus erythematosus is differentiated from other murine models of lupus by a severe monocytosis. The recently identified Y linked autoimmune accelerator locus, Yaa, which is fundamental to accelerated disease in male BXSB mice, is required for the monocytic phenotype in BXSB. It has also recently been shown to induce monocytosis in combination with the Nba2 locus from NZB. To dissect the genetic basis and associated pathogenicity of BXSB related monocytosis, a panel of existing congenic mice were studied and a novel sub-congenic mouse B10.Y(BXSB).BXSB-Bxs3 was generated. Monocytosis was found to be caused by an epistatic interaction between Yaa and the telomeric region of chromosome 1, an area of approximately 30 cM. Bxs3 and Yaa together were sufficient to generate monocytosis equivalent to that of BXSB. In contrast to the NZB model, however, where monocytosis tightly correlated with autoantibody production and lethal lupus nephritis, this was not the case in BXSB. While Yaa(+) mice bearing the Bxs3 locus drive monocytosis, glomerulonephritis and autoantibody production, both autoantibody production and nephritis are discreet events that occur in the absence of the Bxs3 locus. Yaa is a pre-requisite for monocytosis, demonstrating a novel synergistic interaction between Yaa and Bxs3. PMID- 17728790 TI - Differential effects of DRB1*0301 and DQA1*0501-DQB1*0201 on the activation and progression of islet cell autoimmunity. AB - Autoimmune diabetes shows extreme variation in age of onset and clinical presentation, although most studies have been done in children with the most severe subtype. Disease risk is strongly associated with HLA-DRB1*0301-DQA1*0501 DQB1*0201 (DR3-DQ2), but it has not been possible to separate the effects of the DR and DQ alleles. We have identified a large Bedouin kindred in which a high prevalence of islet autoimmunity is associated with two different DR3 haplotypes, one carrying the usual DQ2 and the other carrying DQA1*0102-DQB1*0502 (DQ5). Results of prospective follow-up studies indicate that DR3 is associated with the initial activation of islet autoimmunity whereas DQ2 is associated with early onset and severe clinical disease. The association signals map to a 350-kb interval, thus implicating primary effects for DR3 and DQ2. Overall, our results emphasize the importance of prospective genetic studies that examine the full range of variation in the initiation, progression and expression of autoimmune disease. PMID- 17728792 TI - Genomic view of IFN-alpha response in pre-autoimmune NZB/W and MRL/lpr mice. AB - Interferon (IFN)-alpha is involved in the pathogenesis of systemic lupus erythematosus. Studies in murine lupus models have revealed that type I IFN exerts either a protective effect in MRL/lpr, or can detrimentally impact disease progression, as in NZB/W mice. To understand this paradox, we examined the kinetic global gene expression in pre-autoimmune NZB/W-, MRL/lpr- and normal BALB/c-derived splenic mononuclear cells following ex vivo IFN-alpha treatment. Analysis of IFN-alpha-induced gene expression patterns revealed genes associated with antiproliferative activity of IFN-alpha including CDKN1A, GADD45B, pituitary tumor-transforming 1, SCOTIN, ataxia telangiectasia-mutated homolog and calcyclin binding protein were upregulated in MRL/lpr and/or BALB/c mice. Of IFN-alpha induced genes differentially expressed in NZB/W vs BALB/c and MRL/lpr mice at 3 h time point, enhanced expression of CCND1, cyclin D2, matrix metalloproteinase 13 and a panel of cytokines and chemokines and impaired expression of negative inflammatory regulators CD69 and an Src family kinase hemopoietic cell kinase were notable. Interestingly, the splenic mononuclear cells from the NZB/W not MRL/lpr lupus-prone mice at the pre-autoimmune stage before ex vivo IFN-alpha treatment, have increased expression of many known IFN-regulated genes. These results provide a unique genomic view of ex vivo IFN-alpha response in two lupus prone models, and help to have an insight into the role of IFN-alpha in lupus pathogenesis. PMID- 17728793 TI - What are the occlusal outcomes for unilateral cleft lip and palate patients? A national project in the UK. AB - AIM: This national project assessed the orthodontic outcome for unilateral cleft lip and palate (UCLP) patients in the UK. METHOD: Six consecutively treated fixed appliance cases where orthognathic surgery was not undertaken were assessed using the peer assessment rating (PAR) index on orthodontic study models. These cases were submitted by NHS consultant orthodontists undertaking treatment on patients with cleft lip and/or palate. SETTING: UK NHS consultant-led hospital service. RESULTS: The mean reduction in PAR score was 69% + or - 22. The mean start PAR score was 41 + or - 11. The mean end of treatment PAR was 12 + or - 9. The proportion of cases where the score was worse or no different was 7.5%. CONCLUSION: The mean percentage PAR reduction compares well with other national projects looking at outcome from patients treated in the hospital service. The mean PAR reduction could be used as a benchmark for outcome in UCLP orthodontic treatments in future audit projects and the annual consultant appraisal process. PMID- 17728794 TI - Comparative biology of rAAV transduction in ferret, pig and human airway epithelia. AB - Differences between rodent and human airway cell biology have made it difficult to translate recombinant adeno-associated virus (rAAV)-mediated gene therapies to the lung for cystic fibrosis (CF). As new ferret and pig models for CF become available, knowledge about host cell/vector interactions in these species will become increasingly important for testing potential gene therapies. To this end, we have compared the transduction biology of three rAAV serotypes (AAV1, 2 and 5) in human, ferret, pig and mouse-polarized airway epithelia. Our results indicate that apical transduction of ferret and pig airway epithelia with these rAAV serotypes closely mirrors that observed in human epithelia (rAAV1>rAAV2 congruent withrAAV5), while transduction of mouse epithelia was significantly different (rAAV1>rAAV5>>rAAV2). Similarly, ferret, pig and human epithelia also shared serotype-specific differences in the polarity (apical vs basolateral) and proteasome dependence of rAAV transduction. Despite these parallels, N-linked sialic acid receptors were required for rAAV1 and rAAV5 transduction of human and mouse airway epithelia, but not ferret or pig airway epithelia. Hence, although the airway tropisms of rAAV serotypes 1, 2 and 5 are conserved better among ferret, pig and human as compared to mouse, viral receptors/co-receptors appear to maintain considerable species diversity. PMID- 17728795 TI - Retroviral gene transfer of tissue-type plasminogen activator targets thrombolysis in vitro and in vivo. AB - Patients usually have serious complications of thrombosis and bleeding by eating anticoagulation medicine for their residual lives after mechanical valve replacement operation. Tissue-type plasminogen activator (tPA) could target thrombolysis by activating plasminogen to fibrinolysin. In this study, we recombined a retroviral vector pLEGFP-N1-tPA and cultured purified packaging cells PT67/pLEGFP-N1-tPA to produce high-titer retrovirus. In vitro, two target cells, endothelial cell of umbilical vein (ECUV) 304 and heart muscle cell (HMC) that consist of endocardium and heart muscle, were infected by pLEGFP-N1-tPA. The results demonstrated that exogenous tPA was successfully transferred into ECUV304 and HMC. tPA in the two cells shows significant thrombolysis in plasma plate and the activity and content of tPA were high. Furthermore, in vivo, no thrombus was seen on the surface of Dacron patches (the same material making up a ring of mechanical valve) by tPA locally transferring around Dacron patches that were transplanted in the inferior caval veins of rabbits. tPA was successfully transferred into the local inferior caval vein. Activity and content of tPA were high in local tissue and blood and thrombolysis was effectively demonstrated by tPA rapidly, efficiently and long expressing. This laid the foundation for study and appliance of the tPA gene valve. PMID- 17728797 TI - Achieving blood pressure goals globally: five core actions for health-care professionals. A worldwide call to action. AB - The prevalence of hypertension continues to rise across the world, and most patients who receive medical intervention are not adequately treated to goal. A Working Group including representatives of nine international health-care organizations was convened to review the barriers to more effective blood pressure control and propose actions to address them. The group concluded that tackling the global challenge of hypertension will require partnerships among multiple constituencies, including patients, health-care professionals, industry, media, health-care educators, health planners and governments. Additionally, health-care professionals will need to act locally with renewed impetus to improve blood pressure goal rates. The Working Group identified five core actions, which should be rigorously implemented by practitioners and targeted by health systems throughout the world: (1) detect and prevent high blood pressure; (2) assess total cardiovascular risk; (3) form an active partnership with the patient; (4) treat hypertension to goal and (5) create a supportive environment. These actions should be pursued with vigour in accordance with current clinical guidelines, with the details of implementation adapted to the economic and cultural setting. PMID- 17728798 TI - Single-nucleotide polymorphisms near the microsatellite D17S1303 and the development of hypertension in a 6-year longitudinal study. AB - This study examined the association of tagging single-nucleotide polymorphisms (SNPs) in the 130 kb region surrounding the microsatellite D17S1303 on chromosome 17p12 with the development of hypertension after 6 years in a cohort of 232 Hong Kong Chinese adults. Four SNPs (rs9899362, rs10491093, rs11658572 and rs9913883) were associated with the development of hypertension (P<0.05), but these associations require confirmation in future studies. Nevertheless, our study provides further evidence for the presence of an unidentified gene or a regulatory element predisposing to hypertension in a region approximately 24 kb downstream of D17S1303. PMID- 17728796 TI - Simian immunodeficiency virus lentivector corrects human X-linked chronic granulomatous disease in the NOD/SCID mouse xenograft. AB - X-linked chronic granulomatous disease (X-CGD) is a primary immunodeficiency caused by mutations in the phagocyte nicotinamide dinucleotide phosphate oxidase catalytic subunit gp91(phox). Gene therapy targeting hematopoietic stem cells (HSCs) can correct CGD, but permanent correction remains a challenge. Lentiviral vectors have become attractive tools for gene transfer, and they may have the potential to transduce very primitive HSCs. We used a self-inactivating RD114/TR pseudotyped simian immunodeficiency virus (SIVmac)-based vector encoding human gp91(phox) for ex vivo transduction of peripheral blood-mobilized stem cells (PBSCs) from patients with X-CGD. In PBSCs from two patients, ex vivo transduction efficiencies of 40.5 and 46% were achieved, and correction of oxidase activity was observed in myeloid cells differentiating in culture. When transduced PBSCs from these patients were transplanted into nonobese diabetic/severe combined immunodeficient mice and compared to normal control, 10.5 and 7.3% of the human myeloid cells in bone marrow developing at 6 weeks from the human xenografts expressed the gp91(phox) transgene. Sustained functional correction of oxidase activity was documented in myeloid cells differentiated from engrafted transduced PBSCs. Transgene marking was polyclonal as assessed by vector integration site analysis. These data suggest that RD114/TR SIVmac-based vectors might be suitable for gene therapy of CGD and other hereditary hematologic diseases. PMID- 17728800 TI - Attenuated radial augmentation index is associated with successful long-term antihypertensive treatment. AB - Pulse wave analysis was performed in apparently normal volunteers (n=164) and in essentially hypertensive patients without cardiovascular complications (n=171) using a newly developed non-invasive pulse wave measurement device (HEM-9010AI). Our results suggest that early wave reflections measured by radial augmentation index (AIr) are enhanced in volunteers with systolic blood pressure (SBP) >or= 160 mm Hg compared with the volunteers with their SBP<160 mmHg (98+/-18 vs 88+/ 12, P<0.05). Furthermore, AIr is lower in hypertensive patients with long-term antihypertensive treatment than in those with short-term treatment (84+/-10 vs 89+/-13, P<0.01). PMID- 17728799 TI - Synergistic effect of angiotensin II type 1 receptor and endothelial nitric oxide synthase gene polymorphisms on arterial stiffness. AB - Angiotensin II and nitric oxide belong to important factors in the functional and structural changes of vessel wall, leading to its increased stiffness. We investigated, whether common mutations of angiotensin II type 1 receptor (AGTR(1)) and endothelial nitric oxide synthase (eNOS) are associated with increased arterial stiffness. Two polymorphisms, A(1166)C of AGTR(1) and T(786)C of Enos, were estimated in a random, general population-based sample of 250 subjects. Arterial stiffness was measured using Sphygmocor as aortic (carotid femoral) and peripheral (femoral-tibial) pulse wave velocities (PWV). Carriers of 3-4 mutant alleles from both polymorphisms, that is, homozygous for both mutations or homozygous for one and heterozygous for the second one, showed significantly higher peripheral PWV (17.92+/-2.40) than those with none or only 1 2 mutant alleles (12.37+/-0.51; P<0.003). Carriers of 3-4 mutant alleles had three times higher risk of having increased peripheral PWV (>or= 13.63 m s(-1), that is, in the top quartile) and this association remained significant after adjustment for potential confounders. No association was found between estimated genotypes and aortic PWV. In conclusion, combination of A(1166)C of AGTR(1) and T(786)C of eNOS mutations increased stiffness of muscular-type arteries. PMID- 17728802 TI - Risk of chronic kidney disease in hypertensive patients with other metabolic conditions. AB - Using a retrospective cohort design and electronic medical records, we examined chronic kidney disease (CKD) risk over a 6-year period among hypertensive patients in relation to the presence of diabetes, hyperlipidaemia and/or high body mass index. After adjusting for age, sex, smoking status and baseline glomerular filtration rate (GFR), hypertensive patients without other metabolic risk factors had a relative risk of CKD (versus normotensive patients) of 2.0 (95% CI 1.8-2.2); hypertensive patients with other metabolic conditions had adjusted relative risks ranging from 2.4 to 2.6 for those without comorbid diabetes, and from 3.3 to 5.5 for those with comorbid diabetes. Our study thus confirms prior research demonstrating elevated CKD risk in hypertensive patients, and suggests that this risk varies substantially in relation to other metabolic conditions, especially diabetes. PMID- 17728801 TI - 'Induction of inflammatory gene expression by THP-1 macrophages cultured in normocholesterolaemic hypertensive sera and modulatory effects of green tea polyphenols'. AB - Hypertension is a disorder controlled by multiple genes and inflammation and vascular remodelling of arteries have been implicated in pathogenesis of this disease. Green tea polyphenols (GrTPs) are rich in antioxidants and are known to inhibit inflammatory responses. A significant time-dependent increase in mRNA expression of both IL-6 and MMP-9 were observed in THP-1 macrophages when cultured in normocholesterolaemic hypertensive sera (P<0.05). PMID- 17728803 TI - Renal artery aneurysms: presentation of five cases. AB - We are presenting clinical characteristics, management and follow-up of five consecutive patients with renal artery aneurysm. Renal artery aneurysms are relatively uncommon, they rarely give rise to clinical manifestations and they are usually found incidentally. However with the introduction of Doppler ultrasound, computed tomography (CT) and magnetic resonance (MR) imaging, the diagnosis of renal artery aneurysms became more frequent. PMID- 17728804 TI - Erectile dysfunction prospectively associated with cardiovascular disease in the Dutch general population: results from the Krimpen Study. AB - The possible relationship between erectile dysfunction and the later occurrence of cardiovascular disease while biologically plausible has been evaluated in only a few studies. Our objective is to determine the relation between ED as defined by a single question on erectile rigidity and the later occurrence of myocardial infarction, stroke and sudden death in a population-based cohort study. In Krimpen aan den IJssel, a municipality near Rotterdam, all men aged 50-75 years, without cancer of the prostate or the bladder, without a history of radical prostectomy, neurogenic bladder disease, were invited to participate for a response rate of 50%. The answer to a single question on erectile rigidity included in the International Continence Society male sex questionnaire was used to define the severity of erectile dysfunction at baseline. Data on cardiovascular risk factors at baseline (age smoking, blood pressure, total- and high-density lipoprotein cholesterol, diabetes) were used to calculate Framingham risk scores. During an average of 6.3 years of follow-up, cardiovascular end points including acute myocardial infarction, stroke and sudden death were determined. Of the 1248 men free of CVD at baseline, 258 (22.8%) had reduced erectile rigidity and 108 (8.7%) had severely reduced erectile rigidity. In 7945 person-years of follow-up, 58 cardiovascular events occurred. In multiple variable Cox proportional hazards model adjusting for age and CVD risk score, hazard ratio was 1.6 (95% confidence interval (CI): 1.2-2.3) for reduced erectile rigidity and 2.6 (95% CI: 1.3-5.2) for severely reduced erectile rigidity. The population attributable risk fraction for reduced and severely reduced erectile rigidity was 11.7%. In this population-based study, a single question on erectile rigidity proved to be a predictor for the combined outcome of acute myocardial infarction, stroke and sudden death, independent of the risk factors used in the Framingham risk profile. PMID- 17728805 TI - Measurement of the relationship between perceived and computed color differences. AB - Using simulated data sets, we have analyzed some mathematical properties of different statistical measurements that have been employed in previous literature to test the performance of different color-difference formulas. Specifically, the properties of the combined index PF/3 (performance factor obtained as average of three terms), widely employed in current literature, have been considered. A new index named standardized residual sum of squares (STRESS), employed in multidimensional scaling techniques, is recommended. The main difference between PF/3 and STRESS is that the latter is simpler and allows inferences on the statistical significance of two color-difference formulas with respect to a given set of visual data. PMID- 17728807 TI - Optical density of the aging human ocular media in the visible and the UV. AB - We analyzed the literature on the absorption in the young and aging human eye media. Five templates were derived to provide an adequate description of the spectra from 300 to 700 nm for the lens, cornea, aqueous, and vitreous. Two templates were found in all media. They stand for Rayleigh scatter and the absorbance of tryptophan. Three additional templates for the lens represent absorbance in kynurenine derivatives, such as 3-hydroxykynurenine glucoside (3HKG), and absorbance in two substances found at older age. Except for Rayleigh scatter, all templates have a Gaussian shape. Aging-trend functions were derived that show a linear slope on an age-squared scale. The result can be used to correct for media losses in visual perception tasks, in fundus reflectometry, and in studies on light damage. PMID- 17728806 TI - Effects of surround articulation on lightness depend on the spatial arrangement of the articulated region. AB - We investigated the effect of surround articulation on the perceived lightness of a target disk. Surround articulation was manipulated by varying either the number of wedges in a surround consisting of wedges of alternating luminance or the number of checks in a surround consisting of a radial checkerboard pattern. In most conditions, increased articulation caused incremental targets to appear lighter and decremental targets to appear darker. But increasing the surround articulation in a way that did not increase the number of target-coaligned edges in the display did not affect the target lightness. We propose that the effects of surround articulation depend on the relationship between the orientations and contrast polarities of the target edges and those of edges present within the surround. PMID- 17728808 TI - Aftereffect of contrast adaptation to a chromatic notched-noise stimulus. AB - One of the most challenging topics in the study of human color vision is the investigation of the number of hue-selective channels that are necessary for the representation of color appearance at the post-opponent level and the bandwidth of their sensitivity. The present study aims to elucidate this issue by using a chromatic version of the notch-filtered noise (herein, notched-noise) stimulus for contrast adaptation. After adaptation to this stimulus, some color-sensitive mechanisms that selectively respond to missing hues in the notched-noise stimulus may remain sensitive, while the other mechanisms may be desensitized. The shifts in the color appearance of a gray test field after the adaptation to such a notched noise were measured using the method of adjustment. The results showed systematic shifts in the hue and saturation. They showed neither point nor line symmetric profiles with respect to the achromatic point in an isoluminant plane. The fittings of the results, obtained by using a tiny numerical model for assessing the hue-selective mechanisms, suggested that there are at least two narrowly tuned and at least three broadly tuned mechanisms. The narrowly tuned mechanisms are the most sensitive along the blue and yellow directions. The present study confirmed the variation of multiple channels at the post-opponent level and suggested that this variation may be responsible for the processing of color appearance. PMID- 17728809 TI - Structural sparseness and spatial phase alignment in natural scenes. AB - The Fourier phase spectrum plays a central role regarding where in an image contours occur, thereby defining the spatial relationship between those structures in the overall scene. Only a handful of studies have demonstrated psychophysically the relevance of the Fourier phase spectrum with respect to human visual processing, and none have demonstrated the relative amount of local cross-scale spatial phase alignment needed to perceptually extract meaningful structure from an image. We investigated the relative amount of spatial phase alignment needed for humans to perceptually match natural scene image structures at three different spatial frequencies [3, 6, and 12 cycles per degree (cpd)] as a function of the number of structures within the image (i.e., "structural sparseness"). The results showed that (1) the amount of spatial phase alignment needed to match structures depends on structural sparseness, with a bias for matching structures at 6 cpd and (2) the ability to match partially phase randomized images at a given spatial frequency is independent of structural sparseness at other spatial frequencies. The findings of the current study are discussed in terms of a network of feature integrators in the human visual system. PMID- 17728810 TI - Color constancy from blackbody illumination. AB - We present a theoretical analysis of what we believe to be a new color constancy method that inputs two chromaticities of an identical surface taken under two blackbody illuminations. By using the Planck formula for modeling spectra of outdoor illumination and by assuming that a narrowband camera sensitivity function is sufficiently narrow, surface colors can be estimated mathematically. Experiments with simulation and real data have been conducted to evaluate the effectiveness of the method. The results showed that although this method is a perfect vehicle for simulation data, it produces significant errors with real data. A thorough investigation of the cause of errors indicates how important the assumptions on both blackbody illuminations and narrowband camera sensitivities are to the method. Finally, we discuss the robustness of our method and the limitation of solving color constancy using the illumination constraint. PMID- 17728811 TI - Multiframe phase-diversity algorithm for active imaging. AB - A multiframe phase-diversity algorithm for imaging through the turbulent atmosphere tailored to the statistics of coherent light is developed and presented. The problem is posed as a maximum likelihood estimation where pupil plane intensity data and atmospheric statistics are used to regularize the inverse problem. Reconstruction results characterized by residual mean square error are presented for varying detection parameters. The resulting algorithm appears to be robust under detection noise processes and results in significant improvement of processed images. PMID- 17728813 TI - Fundamental diffraction limitations in a paraxial 4-f imaging system with coherent and incoherent illumination. AB - In the usual model of an imaging system, only the effects of the aperture stop are considered in determining diffraction-limited system performance. In fact, diffraction at other stops--those associated with different lens elements, for example--can also affect system performance and cause the imaging to be space variant, even in the absence of vignetting in the conventional ray optics sense. For the 4-f imaging system investigated in this paper, the severity of the space variance depends on the relative sizes of the two lens stops and the aperture stops. If the diameters of the lenses are equal, the aperture of the first lens has a greater effect on system performance than does that of the second. PMID- 17728812 TI - Speckle reduction in optical coherence tomography images using digital filtering. AB - Speckle noise is a ubiquitous artifact that limits the interpretation of optical coherence tomography images. Here we apply various speckle-reduction digital filters to optical coherence tomography images and compare their performance. Our results indicate that shift-invariant, nonorthogonal wavelet-transform-based filters together with enhanced Lee and adaptive Wiener filters can significantly reduce speckle and increase the signal-to-noise ratio, while preserving strong edges. The speckle reduction capabilities of these filters are also compared with speckle reduction from incoherent angular compounding. Our results suggest that by using these digital filters, the number of individual angles required to attain a certain level of speckle reduction can be decreased. PMID- 17728814 TI - Image-based prediction of imaging and vision performance. AB - Some scenarios require performance estimation of an imaging or a computer vision system prior to its actual operation such as in system design, as well as in tasks of high risk or cost. To predict the performance, we propose an image-based approach that accounts for underlying image-formation processes while using real image data. We give a detailed description of image formation from scene photons to image gray levels. This analysis includes all the optical, electrical, and digital sources of signal distortion and noise. On the basis of this analysis and our access to the camera parameters, we devise a simple image-based algorithm. It transforms a baseline high-quality image to render an estimated outcome of the system we wish to operate or design. We demonstrate our approach on thermal imaging systems (infrared spectrum, 3-5 microm). PMID- 17728815 TI - Fractional Fourier transforms, symmetrical lens systems, and their cardinal planes. AB - We study the relation between optical lens systems that perform a fractional Fourier transform (FRFT) with the geometrical cardinal planes. We demonstrate that lens systems symmetrical with respect to the central plane provide an exact FRFT link between the input and output planes. Moreover, we show that the fractional order of the transform has real values between 0 and 2 when light propagation is produced between principal planes and antiprincipal planes, respectively. Finally, we use this new point of view to design an optical lens system that provides FRFTs with variable fractional order in the range (0,2) without moving the input and output planes. PMID- 17728816 TI - Experimental observation of fractional Fourier transform for a partially coherent optical beam with Gaussian statistics. AB - We report the experimental observation of the fractional Fourier transform (FRT) for a partially coherent optical beam with Gaussian statistics [i.e., partially coherent Gaussian Schell-model (GSM) beam]. The intensity distribution (or beam width) and the modulus of the square of the spectral degree of coherence (or coherence width) of a partially coherent GSM beam in the FRT plane are measured, and the experimental results are analyzed and agree well with the theoretical results. The FRT optical system provides a convenient way to control the properties, e.g., the intensity distribution, beam width, spectral degree of coherence, and coherence width, of a partially coherent beam. PMID- 17728817 TI - Optimization of holographic storage with modulated recording beams in a thick polyvinyl alcohol/acrylamide photopolymer. AB - In a holographic photopolymer system, the storage properties were often limited due to the attenuation in depth of light during the recording step. To obtain smaller values of the depth attenuation profiles in 1 mm thick polyvinyl alcohol/acrylamide (PVA/acrylamide) photopolymers, we used a triangle prism, sitting one face tilted at 13.7 degrees to the axis within the focus of a lens, to modulate the distribution of recording beams. Doing this permitted larger refractive index modulation depth to be achieved, and larger dynamic range (M#=9.2) was obtained in the PVA/acrylamide photopolymers. PMID- 17728818 TI - Calculation of diffraction patterns on a spatial surface. AB - An approximated formulation of the Fresnel function is put forward and is used in the approximate evaluation of the Fresnel diffraction integral. By comparing the approximate formulation with the experimental measurements and calculations in the fast Fourier transform (FFT) method of the diffraction integral, we demonstrate that the proposed method is sufficiently accurate for calculating the Fresnel diffraction. For the diffraction field calculation on a spatial surface, the calculation speed of this method is usually higher than that of the FFT method. PMID- 17728819 TI - Diffraction of a finite-radius plane wave and a Gaussian beam by a helical axicon and a spiral phase plate. AB - We derive what we believe to be new analytical relations to describe the Fraunhofer diffraction of the finite-radius plane wave by a helical axicon (HA) and a spiral phase plate (SPP). The solutions are deduced in the form of a series of the Bessel functions for the HA and a finite sum of the Bessel functions for the SPP. The solution for the HA changes to that for the SPP if the axicon parameter is set equal to zero. We also derive what we believe to be new analytical relations to describe the Fresnel and Fraunhofer diffraction of the Gaussian beam by a HA are derived. The solutions are deduced in the form of a series of the hypergeometric functions. We have fabricated by photolithography a binary diffractive optical element (a HA with number n=10) able to produce in the focal plane of a spherical lens an optical vortex, which was then used to perform rotation of several polystyrene beads of diameter 5 microm. PMID- 17728820 TI - Light scattering from particles located under a rough dielectric layer. AB - A discussion is presented of the effect of roughness on the detectability of subsurface particles by means of the light-scattering method. We have studied the scattering of light by calibrated spheres located under a slightly rough dielectric surface both experimentally and theoretically. In our experiments, the scattering from slightly rough layers with nonresonant particles was dominated by the roughness, and the scattering diagram did not bear any discernible indications of the spheres. However, at resonance, the subsurface particles manifested themselves by an increase in the total scattered intensity and by well pronounced maxima in the angular dependence of both the scattering diagram and the backscattered intensity. Theoretical calculations show that the angular positions of the maxima in the scattering diagram are essentially determined by the interference of fields scattered by the particles and by the surface, whereas the contribution of the multiple interparticle scattering is negligible. By contrast, the oscillations in the angular dependence of the backscattered intensity are due primarily to the scattering between neighboring spheres. PMID- 17728821 TI - Quantitative spectrophotometry of scattering media via frequency-domain and constant-intensity measurements. AB - The attenuation of light by scattering and absorbing media is nonlinearly dependent upon the absorption coefficient, since detected light has experienced many different flight times. The frequency response of such a sample to modulated light is also nonlinear. We derive an expression for the attenuation that includes both the absorption coefficient and the modulation frequency. Its form is a power series whose coefficients are the cumulants of the temporal point spread function (TPSF). Recasting this expression in terms of intensity leads to a similar expression with the cumulants replaced by the moments of the TPSF. A means of exploiting this relationship to produce estimates of the absolute concentration of the absorbing species is suggested. PMID- 17728822 TI - Adaptive laser beam projection on an extended target: phase- and field-conjugate precompensation. AB - The problem of adaptive laser beam projection onto an extended object (target) having a randomly rough surface in an optically inhomogeneous medium (atmosphere) is analyzed. Outgoing beam precompensation is considered through conjugation of either the target-return wave phase or the complex field. It is shown that in the presence of "frozen" turbulence, both phase-conjugate (PC) and field-conjugate (FC) precompensation can result in a superfocusing effect, which suggests the possibility of achieving a brighter target hit spot in volume turbulence than in vacuum. This superfocusing effect is significantly more distinct for FC precompensation. In the quasi-stationary case (slowly moving turbulence or target), PC and FC beam control lead to enhanced intensity fluctuations at the target surface associated with intermittent formation and disintegration of bright target hit spots that sporadically attach to the extended target surface. This intensity fluctuation level exceeds intensity fluctuations in the absence of beam control and is higher for FC precompensation. In the nonstationary case, both PC and FC lead to an increase of beam width and centroid wander at the extended target surface compared with conventional projection of a collimated or focused beam. PMID- 17728823 TI - Detection of phase singularities with a Shack-Hartmann wavefront sensor. AB - While adaptive optical systems are able to remove moderate wavefront distortions in scintillated optical beams, phase singularities that appear in strongly scintillated beams can severely degrade the performance of such an adaptive optical system. Therefore the detection of these phase singularities is an important aspect of strong-scintillation adaptive optics. We investigate the detection of phase singularities with the aid of a Shack-Hartmann wavefront sensor and show that, in spite of some systematic deficiencies inherent to the Shack-Hartmann wavefront sensor, it can be used for the reliable detection of phase singularities, irrespective of their morphologies. We provide full analytical results, together with numerical simulations of the detection process. PMID- 17728824 TI - Design considerations in projection phase-shift moire topography based on theoretical analysis of fringe formation. AB - Moire topography is a well-established optical technique to measure the shape of three-dimensional surfaces, based on the geometric interference between an optical grid and its image deformed by an object surface. The technique produces fringes that represent contours of equal height, and from the recordings of several phase-shifted topograms surface height coordinates can be calculated. To perform these calculations, it is assumed that object height variation is small in comparison with the measurement setup dimensions, and this approximation leads to systematic errors in measurement accuracy. We present the mathematical description of the fringe formation process in projection moire topography, and on the basis of these equations we establish the relation between setup geometry and upper limits of the systematic measurement errors. We derive the equations that determine design specifications needed to reduce the effects of approximations to be below the measurement resolution of the setup. It is shown that setup geometry should be adapted to the gray-scale measurement resolution of the imaging system. We show that, using an iterative correction from one fringe order to the next, measurement accuracy can be maintained over the entire object depth. PMID- 17728825 TI - Fluorescent molecular tomographic image reconstruction based on the Green's function. AB - The rapid and accurate computation of the Jacobian matrix, which is usually computationally intensive, is of critical importance for the reconstruction problem of fluorescent molecular tomography (FMT). An extension of the Green's function method for the Jacobian matrix computation suitable for two coupled differential equations is proposed, in combination with the parallel forward computing strategy for FMT image reconstruction. For further acceleration of the reconstruction process without significant quality reduction of the results, we also propose to reconstruct the FMT image on an adaptively refined mesh generated with a priori information incorporated. Experimental results demonstrate that the speed of the reconstruction process can be significantly improved with the proposed overall algorithm. PMID- 17728826 TI - Encircled energy in systems with truncated-Gaussian apertures of different Fresnel numbers. I. Generalization of the Q2n function of E. Wolf and the Yn function of H. H. Hopkins. AB - In his works on diffraction [Proc. R. Soc. London Ser. A204, 533 (1951)], E. Wolf introduced the Q2n function, which enters his expressions for the encircled energy. This quantity specifies the fraction of the total energy within various rings in receiving planes parallel to the geometrical focal plane. In addition to the Q2n function, another special function, called the Yn function, was used in his formulation, which had been introduced by H. H. Hopkins [Proc. Phys. Soc. London Sect. B62, 22 (1949)]. The purpose of this study is to generalize both the Q2n and Yn functions for evaluating the encircled energy in systems of focused truncated Gaussian beams by apertures of different Fresnel numbers and different levels of beam truncation. The generalized Q and Y functions are functions of more than one variable and are applicable to all nonnegative integers m; they may therefore be called the Qm and the Ym functions. Computed results are shown graphically in the form of contour lines of the encircled energy. Part II of this study [J. Opt. Soc. Am. A24, 2033 (2007)] contains an analysis of maximizing beam energy concentration on a target. PMID- 17728827 TI - Encircled energy for systems with truncated-Gaussian apertures of different Fresnel numbers. II. Maximizing beam energy concentration on a target. AB - In Part I of this study [J. Opt. Soc. Am. A24, 2023 (2007)] the Q(2n) functions of E. Wolf and the Y(n) functions of H. H. Hopkins have been generalized for evaluating the fraction of the total energy in systems with focused truncated Gaussian beams by apertures of different Fresnel numbers and different ratios of aperture radius to beam radius. The generalized special functions provide a mathematical basis for a rigorous study of maximizing beam energy concentration on a target. This subject is addressed under two subtitles: (1) active focusing of a Gaussian beam onto a distant target and (2) optimizing photodetection in a focused field. PMID- 17728829 TI - Light polarization under water near sunrise. AB - Dramatic and rapid changes in the intensity and spectrum of light under water at dusk and dawn are well known, but reports regarding the light's polarization at these periods are sparse. Using a rapid spectropolarimeter, we examined the spatial and spectral characteristics of the underwater polarization patterns from sunrise to midday and compared them with a Rayleigh-based model for e-vector orientation and percent polarization. With the Sun near the horizon, the underwater polarization patterns were distinctive. Unlike the polarization at small solar zenith angles, the underwater polarization at large solar zenith angles cannot be predicted by simple Rayleigh scattering, most likely because of the relatively high contribution of skylight. At sunrise, the underwater polarization pattern outside of Snell's window differed from that found during the day in percent polarization, spatial distribution, and wavelength dependence. These unique polarization characteristics may provide a polarization-sensitive animal with a distinct cue for mediating dial vertical migration performed by plankton or with another timing signal. PMID- 17728828 TI - Degree of polarization in Young's double-slit interference experiment formed by stochastic electromagnetic beams. AB - We analyze the behavior of the degree of polarization in the interference field of Young's double-slit experiment. We analyze the degree of polarization in Young's double-slit interference experiment illuminated by stochastic electromagnetic beams. The distribution of the degree of polarization in the interference field for different correlation lengths and different slit widths is investigated. Furthermore, it is shown that the degree of polarization for a fixed observation point may take on values different from those it takes in the slits, depending not only on the value of the correlation length but also on the width of the slit. PMID- 17728830 TI - Monochromatic scalar fields with maximum focal irradiance. AB - The monochromatic scalar fields that achieve the maximum focal irradiance for a given input power and directional spread are found through a variational approach. In two dimensions, the maximum focal irradiance is found to be proportional to the sine of the directional spread as well as the input power. In three dimensions, the corresponding relation is found in parametric form. PMID- 17728831 TI - A three-dimensional degree of polarization based on Rayleigh scattering. AB - A measure of the degree of polarization for the three-dimensional polarization matrix (coherence matrix) of an electromagnetic field is proposed, based on Rayleigh scattering. The degree of polarization at a point is defined as an average, over all scattering directions, of an imagined dipole scattering of the three-dimensional state of polarization. This gives a well-defined purity measure, which, unlike other proposed measures of the three-dimensional degree of polarization, is not a unitary invariant of the matrix. This is demonstrated and discussed for several examples, including a partially polarized transverse beam. PMID- 17728832 TI - Overall degree of coherence for vectorial electromagnetic fields and the Wigner function. AB - We elaborate the overall degree of coherence for vectorial electromagnetic waves within paraxial approximation, expressing it in terms of a polarization Wigner function and the spatial-angular Stokes parameters. PMID- 17728833 TI - Computer simulation of reflective volume grating holographic data storage. AB - The shift selectivity of a reflective-type spherical reference wave volume hologram is investigated using a nonparaxial numerical modeling based on a multiple-thin-layer implementation of a volume integral equation. The method can be easily parallelized on multiple computers. According to the results, the falloff of the diffraction efficiency due to the readout shift shows neither Bragg zeros nor oscillation with our parameter set. This agrees with our earlier study of smaller and transmissive holograms. Interhologram cross talk of shift multiplexed holograms is also modeled using the same method, together with sparse modulation block coding and correlation decoding of data. Signal-to-noise ratio and raw bit error rate values are calculated. PMID- 17728834 TI - Statistical analysis of a scatter plate interferometer. AB - A scatter plate interferometer is analyzed based on the principle of statistical optics for what is to my knowledge the first time. It is shown that the optical complex amplitude distribution of scattered-direct light that is scattered by the first scatter plate and transmitted through the second scatter plate is equivalent to the distribution of direct-scattered light that is transmitted through the first scatter plate and scattered by the second scatter plate if there are no aberrations in the tested optical elements. Then the mechanism producing interference fringes and fringe contrast are discussed by means of a statistical method. It is shown that the fringe pattern depends on the correlation of the transmittance distributions of the two scatter plates and the aberration of the tested lens. The analysis coincides with experimental phenomena. The method used gives a new viewpoint on the principles of scatter plate interferometry and reveals its statistical nature. PMID- 17728835 TI - Ray equation for a spatially variable uniaxial crystal and its use in the optical design of liquid-crystal lenses. AB - To be able to design optical systems (e.g., variable focus or zoom lenses) made from liquid-crystal devices, it is necessary to be able to ray trace in a birefringent medium where the angle of the optical axis is a function of position in the device. To our knowledge, the theory required to achieve this has not previously been published, and we derive a suitable algorithm and give some examples of its use. PMID- 17728836 TI - Precise analysis of combination homogeneous-inhomogeneous-material superresolution filters with double-tunable modes. AB - By using a Jones matrix, the precise expression for the pupil function of a two adjustable-mode superresolving filter, a combination of a radial birefringent plate and a glass annular plate, is obtained. This filter can provide superresolution in both radial and axial adjustment operations, which can supplement each other in setting accuracy and superresolution range in practical use. As an adjustable filter, it is less dependent on wavelength. With the relative radius of the inner plate set to be epsilon=0.52 and the rotating angle set to be 45 degrees , this type of filter can achieve better superresolution performance than the continuous-phase filters reported in Opt. Lett.28, 607 (2003). PMID- 17728838 TI - PPARS and Obesity. PMID- 17728839 TI - Plasticity and anxiety. PMID- 17728840 TI - Genetic regulatory networks. PMID- 17728841 TI - Kidney modelling for FDG excretion with PET. AB - The purpose of this study was to detect the physiological process of FDG's filtration from blood to urine and to establish a mathematical model to describe the process. Dynamic positron emission tomography scan for FDG was performed on seven normal volunteers. The filtration process in kidney can be seen in the sequential images of each study. Variational distribution of FDG in kidney can be detected in dynamic data. According to the structure and function, kidney is divided into parenchyma and pelvis. A unidirectional three-compartment model is proposed to describe the renal function in FDG excretion. The time-activity curves that were picked up from the parenchyma, pelvis, and abdominal aorta were used to estimate the parameter of the model. The output of the model has fitted well with the original curve from dynamic data. PMID- 17728842 TI - The zinc sensing receptor, a link between zinc and cell signaling. AB - Zinc is essential for cell growth. For many years it has been used to treat various epithelial disorders, ranging from wound healing to diarrhea and ulcerative colon disease. The physiological/molecular mechanisms linking zinc and cell growth, however, are not well understood. In recent years, Zn2+ has emerged as an important signaling molecule, activating intracellular pathways and regulating cell fate. We have functionally identified an extracellular zinc sensing receptor, called zinc sensing receptor (ZnR), that is specifically activated by extracellular Zn2+ at physiological concentrations. The putative ZnR is pharmacologically coupled to a Gq-protein which triggers release of Ca2+ from intracellular stores via the Inositol 1,4,5-trisphosphate (IP3) pathway. This, in turn results in downstream signaling via the MAP and phosphatidylinositol 3 kinase (PI3 kinase) pathways that are linked to cell proliferation. In some cell types, e.g., colonocytes, ZnR activity also upregulates Na+/H+ exchange, mediated by Na+/H+ exchanger isoform 1 (NHE1), which is involved in cellular ion homeostasis in addition to cell proliferation. Our overall hypothesis, as discussed below, is that a ZnR, found in organs where dynamic zinc homeostasis is observed, enables extracellular Zn2+ to trigger intracellular signaling pathways regulating key cell functions. These include cell proliferation and survival, vectorial ion transport and hormone secretion. Finally, we suggest that ZnR activity found in colonocytes is well positioned to attenuate erosion of the epithelial lining of the colon, thereby preventing or ameliorating diarrhea, but, by signaling through the same pathways, a ZnR may enhance tumor progression in neoplastic disease. PMID- 17728844 TI - The first once-daily single-tablet regimen for the treatment of HIV-infected patients. AB - Since the first description of AIDS cases over 25 years ago, great strides have been made in the treatment of HIV infection. The pursuit of new and novel therapies is ongoing, and a particular drive to simple regimens with low toxicities has been seen over the last few years. The arrival of the first once daily single-tablet regimen is a noteworthy milestone. ATRIPLA (Bristol-Myers Squibb, Princeton, NJ, and Gilead Sciences, Foster City, CA, USA) is a combination of three drugs that have been well studied and are currently approved as first-line agents internationally. The studies that demonstrate the efficacy and safety of these drugs are reviewed as well as the potential drawbacks. Single tablet regimens are likely to become the therapies of choice for those commencing antiretroviral treatment, and their place in today's management is discussed. PMID- 17728843 TI - Zinc inhibits astrocyte glutamate uptake by activation of poly(ADP-ribose) polymerase-1. AB - Several processes by which astrocytes protect neurons during ischemia are now well established. However, less is known about how neurons themselves may influence these processes. Neurons release zinc (Zn2+) from presynaptic terminals during ischemia, seizure, head trauma, and hypoglycemia, and modulate postsynaptic neuronal function. Peak extracellular zinc may reach concentrations as high as 400 microM. Excessive levels of free, ionic zinc can initiate DNA damage and the subsequent activation of poly(ADP-ribose) polymerase 1 (PARP-1), which in turn lead to NAD+ and ATP depletion when DNA damage is extensive. In this study, cultured cortical astrocytes were used to explore the effects of zinc on astrocyte glutamate uptake, an energy-dependent process that is critical for neuron survival. Astrocytes incubated with 100 or 400 microM of zinc for 30 min showed significant decreases in ATP levels and glutamate uptake capacity. These changes were prevented by the PARP inhibitors benzamide or DPQ (3,4-dihydro-5-[4 (1-piperidinyl)butoxyl]-1(2H)-isoquinolinone) or PARP-1 gene deletion (PARP-1 KO). These findings suggest that release of Zn2+ from neurons during brain insults could induce PARP-1 activation in astrocytes, leading to impaired glutamate uptake and exacerbation of neuronal injury. PMID- 17728845 TI - Pioglitazone and metformin. AB - Pioglitazone and metformin have both proven safe and efficacious in the treatment of type 2 diabetes. Their combination into a single tablet seems logical. This article reviews the data that are available for this combination. Because the tablets are not currently widely available, the review examines some aspects of the effects of both agents separately and in the few trials where they have been administered concurrently, though not as a single pharmaceutical preparation. Based on this evidence, the combination appears therapeutically efficacious and clinically safe. The side effects are not multiplicative and reflect those predictable from monotherapy with either agent. PMID- 17728846 TI - Rufinamide. AB - Rufinamide is a new antiepileptic drug that is effective in acute animal seizure models and also in the kindling model of epilepsy with a high protective index. Its mechanism of action is largely unknown; studies suggest an effect at voltage gated sodium channels, but whether this is its main mode of action remains to be determined. Rufinamide can be administered twice daily and has minimal drug interactions (it does, however, interact with the contraceptive pill). Food markedly increases absorption, which may complicate clinical use. Trials indicate that rufinamide is effective as adjunctive therapy in partial epilepsy and the Lennox-Gastaut syndrome with minimal adverse effects including headache, dizziness and fatigue. In addition, rufinamide has a favorable cognitive side effect profile. However, it remains uncertain whether rufinamide offers significant advantages over other current antiepileptic drugs, and the results of further clinical trials are awaited. PMID- 17728847 TI - Recombinant human keratinocyte growth factor palifermin reduces oral mucositis and improves patient outcomes after stem cell transplant. AB - Oral mucositis, the breakdown of the mucosal lining of the oropharynx, occurs as a result of a toxic insult to the normal epithelium of the oral mucosa. Typically this is seen after exposure to a toxic agent such as radiation or chemotherapy; therefore, it is a frequent problem for patients undergoing treatment for cancer. In clinical trials, mucositis has been reported in up to 98% of patients receiving high-dose chemotherapy followed by hematological stem cell transplant. When mucositis develops it causes severe patient symptoms such as pain, but it is also associated with inferior clinical outcomes including increased infection, narcotic use and even mortality. In clinical trials, palifermin, a recombinant humanized keratinocyte growth factor (rHuKGF), has demonstrated an ability to decrease the incidence and duration of mucositis. In the registrational phase III trial in patients undergoing stem cell transplant for hematological malignancies, only 63% of patients who received palifermin developed World Health Organization grade 3 or 4 mucositis compared to 98% of patients on the placebo arm (1). The patients on the palifermin arm also had a shorter duration of mucositis with significantly decreased pain, use of narcotics, need for total parenteral nutrition and febrile neutropenia. Based on these results, palifermin became the first drug that has been approved by the U.S. Food and Drug Administration (FDA) to decrease the incidence and duration of severe oral mucositis in patients with hematological malignancies receiving high-dose chemotherapy requiring hematopoietic stem cell support. The development of mucositis is also a problem for patients receiving treatment for nonhematological tumors. In clinical trials, mucositis has been reported in over 75% of patients receiving combined chemo /radiotherapy for head and neck cancer or fluorouracil for metastatic colon cancer. Initial phase I and II clinical trials of palifermin have demonstrated a benefit in patients receiving chemotherapy with or without radiation therapy for solid tumors; however, large phase III trials need to be completed before palifermin can gain FDA approval for this indication. PMID- 17728848 TI - Polypodium leucotomos extract: a nutraceutical with photoprotective properties. AB - Ultraviolet (UV) irradiation causes multifaceted damage to the skin and adjacent tissue layers, and is one of the leading causes of premature skin aging, immunosuppression and carcinogenesis. Photoprotection can be achieved by the use of sunscreens and also by systemically administered compounds that fight the deleterious biological effects of UV exposure, or preferably both. In this review, we summarize the current knowledge on the tissue, cellular and molecular mechanisms underlying the photoprotective effect of Polypodium leucotomos fern extract. P. leucotomos blocked the deleterious effect of UV irradiation both in vivo and in vitro. The molecular basis of photoprotection relies on its ability to inhibit free radical generation, prevent photodecomposition of both endogenous photoprotective molecules and DNA, and prevent UV-induced cell death. Its complete loss of toxicity combined with its multifactor protection makes it a valuable tool not only for direct photoprotection, but also as an efficacious adjuvant to phototherapy of various skin diseases. PMID- 17728849 TI - Pioglitazone hydrochloride/glimepiride. AB - The combination of pioglitazone hydrochloride, a thiazolidinedione, and glimepiride, a sulfonylurea, has been approved in many countries worldwide as an oral agent for the management of type 2 diabetes. Glimepiride stimulates insulin secretion from the pancreas with a decreased risk of hypoglycemia compared to glyburide. Pioglitazone increases glucose uptake in the periphery while decreasing glucose production by the liver. Combined, the two agents increase the body's sensitivity to insulin to reduce hemoglobin A1c levels by 1-2%. Pioglitazone and glimepiride also produce favorable effects on lipid profiles and blood pressure. Additionally, pioglitazone has proven to decrease the risk of certain cardiovascular events, providing evidence for macrovascular benefits. Side effects are minimal with pioglitazone and glimepiride, with weight gain and edema providing the most discomfort and complications. Patients must be monitored for the development of heart failure, though the risk is small. Guidelines are in place to limit patient selection for the use of pioglitazone based on cardiac risk factors. In general, pioglitazone and glimepiride are well tolerated. PMID- 17728852 TI - Beta-amino acid-containing hybrid peptides--new opportunities in peptidomimetics. AB - Hybrid peptides consisting of alpha-amino acids with judiciously placed beta amino acids show great promise as peptidomimetics in an increasing range of therapeutic applications. This reflects a combination of increased stability, high specificity and relative ease of synthesis. PMID- 17728850 TI - Drug-induced pancreatitis: a practical review. AB - Although numerous drugs have been implicated in the etiology of acute pancreatitis, literature on various aspects of drug-induced pancreatitis is sparse and limited mostly to case reports. Accurate diagnosis and management of this rare entity can be a challenge. This review discusses the clinical and epidemiological features of drug-induced pancreatitis, commonly associated drugs and conditions, possible pathogenic mechanisms, and a systematic approach to the diagnosis and management of drug-induced pancreatitis. PMID- 17728853 TI - Utilisation of plant viruses in bionanotechnology. AB - Bionanoscience/technology sits at the interface of chemistry, biology, physics, materials science, engineering and medicine and involves the exploitation of biomaterials, devices or methodologies on the nanoscale. One sub-field of bionanoscience/technology is concerned with the exploitation of biomaterials in the fabrication of new nano-materials and/or -devices. In this Perspective we describe examples of how plant viruses, focusing particularly on cowpea mosaic virus, a naturally occurring pre-formed sphere-like nanoparticle, are being used as templates and/or building blocks in bionanoscience and indicate their potential for future application. PMID- 17728854 TI - Intramolecular cation-pi interaction in organic synthesis. AB - Controlling molecular conformation is a significantly important issue in a wide variety of organic reactions because the ground state structure is significantly responsible for the transition one. As observed in enzymes and proteins, the cation-pi interaction plays a key role in the formation of the tertiary structure and the biochemical processes. Therefore, the cation-pi interaction would be a promising conformation-controlling tool not only in large molecules, but also in small molecules due to its stronger interaction force. This article describes the utility of the intramolecular cation-pi interaction in various organic syntheses with evidence for the existence of the cation-pi interactions. PMID- 17728855 TI - Highly enantioselective direct aldol reaction catalyzed by cinchona derived primary amines. AB - Highly enantioselective aldol reactions of aldehydes with cyclic ketones catalyzed by a primary amine derived from cinchonine are reported. Aromatic aldehydes reacted with various cyclic ketones cleanly to afford the anti-aldol adducts in up to 99% yield, with good diastereoselectivities (up to 9 : 1) and excellent enantioselectivities (up to 99% ee). PMID- 17728856 TI - 3-Azidodifluoromethyl-3H-diazirin-3-yl group as an all-in-one functional group for radioisotope-free photoaffinity labeling. AB - The 3-azidodifluoromethyl-3H-diazirin-3-yl group was designed and synthesized as an all-in-one functional group for radioisotope-free photoaffinity labeling. PMID- 17728857 TI - A novel proton-selective sensor based on a sugar with hinge flexibility. AB - A hinge sugar, a 2,4-diamino-2,4-dideoxy-beta-D-xylopyranoside derivative, turns its four equatorial substituents into axial orientations through a (4)C(1)-to (1)C(4) ring flip in response to chelation to a metal ion. This hinge-like motion enables two components attached at the 1- and 3-positions to switch between far and near states. In this study, we examined the effect of N-alkylation on the bendability of the hinge molecule and synthesized a 2,4-dipyrenylmethyl derivative as a proton-selective sensor. (1)H NMR studies showed that N alkylations of the hinge sugar facilitated (1)C(4) formation in the presence of an acid, probably because the increased basicity of the amino group promoted the intramolecular hydrogen bond between the 2- and 4-amino substituents, whereas chelation to a metal ion was hampered by the increased bulkiness. In accordance with the above results, N,N'-dipyrenylmethyl hinge sugar 3 emitted excimer fluorescence (445 nm) owing to the pyrene stacking as a result of the (1)C(4) formation at lower concentrations of trifuluoroacetic acid (TFA), while no significant changes in fluorescence spectra were observed when metal ions were added. Increase of the monomer fluorescence (375 nm) at higher TFA concentrations was also observed. These observations indicate that 3 could be used as a proton selective sensor that covers a wide range of proton concentrations through monitoring of the two fluorescence maxima. PMID- 17728858 TI - Stereoselective synthesis of 3,4-disubstituted and 3,4,5-trisubstituted piperidines by Lewis acid-catalysed ene cyclisation of 4-aza-1,7-dienes. AB - The thermal or Lewis acid-catalysed ene cyclisation of a variety of 4-aza-1,7 dienes afforded 3,4-disubstituted or 3,4,5-trisubstituted piperidines. Activation of the enophile with a single ester facilitated a thermal ene cyclisation, although the reaction was not amenable to Lewis acid catalysis. With other activating groups on the enophile it was found that Lewis acid catalysis was facile, although there was a fine balance between the desired ene cyclisation and the competing hetero-Diels-Alder reaction, with the product distribution being influenced by the activating group on the enophile, the nature of the ene component, and the Lewis acid used. Activation of the enophile with an oxazolidinone function facilitated Lewis acid-catalysed cyclisation to afford mixtures of ene and hetero-Diels-Alder products. Activating the enophile with two ester groups gave a substrate that underwent a very facile ene cyclisation catalysed by MeAlCl(2) to give the corresponding trans 3,4-disubstituted piperidines with diastereomeric ratios of >200 : 1. PMID- 17728859 TI - Cerium complexes of cyclodextrin dimers as efficient catalysts for luminol chemiluminescence reactions. AB - The chemiluminescence of a luminol-H(2)O(2) system is found to be remarkably enhanced by the Ce(IV) complexes of EDTA-bridged cyclodextrin dimers. The dimers were proved to work much more efficiently than the corresponding monomer. The cavity shape of cyclodextrin moieties and their cooperation displayed an important role in amplifying the chemiluminescence. Further modification of either the cyclodextrin rims or the EDTA linker altered significantly the catalytic abilities of the cyclodextrin dimers, and the examination of the effect of substituents on the chemiluminescence outputs suggested that the proximity between the cyclodextrin cavity and the metallic center might account for the amelioration of the chemiluminescence output. PMID- 17728860 TI - Dual aromatase-sulfatase inhibitors based on the anastrozole template: synthesis, in vitro SAR, molecular modelling and in vivo activity. AB - The synthesis and biological evaluation of a series of novel Dual Aromatase Sulfatase Inhibitors (DASIs) are described. It is postulated that dual inhibition of the aromatase and steroid sulfatase enzymes, both responsible for the biosynthesis of oestrogens, will be beneficial in the treatment of hormone dependent breast cancer. The compounds are based upon the Anastrozole aromatase inhibitor template which, while maintaining the haem ligating triazole moiety crucial for enzyme inhibition, was modified to include a phenol sulfamate ester motif, the pharmacophore for potent irreversible steroid sulfatase inhibition. Adaption of a synthetic route to Anastrozole was accomplished via selective radical bromination and substitution reactions to furnish a series of inhibitory aromatase pharmacophores. Linking these fragments to the phenol sulfamate ester moiety employed S(N)2, Heck and Mitsunobu reactions with phenolic precursors, from where the completed DASIs were achieved via sulfamoylation. In vitro, the lead compound, 11, had a high degree of potency against aromatase (IC(50) 3.5 nM), comparable with that of Anastrozole (IC(50) 1.5 nM) whereas, only moderate activity against steroid sulfatase was found. However, in vivo, 11 surprisingly exhibited potent dual inhibition. Compound 11 was modelled into the active site of a homology model of human aromatase and the X-ray crystal structure of steroid sulfatase. PMID- 17728861 TI - Synthesis and binding properties of divalent and trivalent clusters of the Lewis a disaccharide moiety to Pseudomonas aeruginosa lectin PA-IIL. AB - The synthesis of oligomeric glycocomimetics has been performed for targeting the Pseudomonas aeruginosa PA-IIL lectin, which is of therapeutical interest for anti adhesive treatment. The disaccharide alpha-L-Fucp-(1-->4)-beta-D-GlcNAc, which is a high-affinity ligand of the lectin, has been coupled to dimeric and trimeric linkers with various lengths and geometries. A series of linear dimers displayed an efficient clustering effect and a very strong affinity, with a lower dissociation constant of 90 nM. The trimeric compound was less efficient in inhibition assays but displayed high affinity in solution. Titration microcalorimetry and molecular modeling allowed in-depth analysis and rationalization of the binding data. These glycoclusters could act by crosslinking the lectins present on the surface of bacteria and therefore interfere with host recognition or biofilm formation. PMID- 17728862 TI - Palladium-catalyzed copper(I)-mediated cross-coupling of arylboronic acids and 2(1H)-pyrazinones facilitated by microwave irradiation with simultaneous cooling. AB - The application of a palladium-catalyzed Cu(I)-mediated Liebeskind-Srogl protocol for the decoration of the 2(1H)-pyrazinone scaffold resulted in significantly improved yields and rates when performed under microwave irradiation with simultaneous cooling. PMID- 17728863 TI - Organocatalytic asymmetric destruction of 1-benzylated Reissert compounds catalysed by quaternary cinchona alkaloids. AB - The enantiomeric enrichment of racemic 1-benzylated Reissert compounds under organocatalytic biphasic conditions is presented. The enrichment is the consequence of an asymmetric destruction of the racemic compounds resulting in the formation of the corresponding 1-benzylated isoquinolines. The highest selectivity has been achieved using quaternary cinchona alkaloids as phase transfer catalysts. The resolution of a number of racemic 1-benzylated Reissert compounds reveals a significant substrate dependence and a proposal for the mechanism of the reaction is presented. PMID- 17728864 TI - A mechanistic study of the dynamic quenching of the excited state of europium(III) and terbium(III) macrocyclic complexes by charge- or electron transfer. AB - Dynamic quenching of the metal-based excited state of Eu(III) and Tb(III) complexes of sixteen different macrocyclic ligands has been studied. Quenching by urate, ascorbate and selected catechols is most effective for Tb(III) systems, and involves intermediate formation of an excited state complex (exciplex) between the electron-poor heterocyclic sensitising moiety incorporated into the ligand (tetraazatriphenylene, azaxanthone or a pyrazoyl-azaxanthone) and the electron-rich reductant. The process is sensitive to steric inhibition created by the local ligand environment; quenching is reduced as temperature increases as exciplex formation is entropically disfavoured. In contrast, iodide quenches each complex studied according to a classical collisional encounter model; increasing temperature enhances the rate of quenching, and the process is more sensitive to local electrostatic fields generated by ligand substitution, conforming to a traditional Stern-Volmer kinetic model. Quenching may be inhibited by protein association, allowing the identification of candidates for use as optical imaging probes in cellulo. PMID- 17728865 TI - Synthesis, structure and stereochemistry of quinoline alkaloids from Choisya ternata. AB - A range of seventeen quinoline alkaloids, involving several types of oxidations during their biosynthetic pathways, have been isolated from leaves of Choisya ternata. In addition to the nine known quinoline alkaloids, eight new members of the furoquinoline family, derived mainly from prenylation at C-5 (including two novel hydroperoxides), have been identified. The absolute configurations and enantiopurity values of all chiral quinoline alkaloids have been determined. One of the isolated alkaloids, 7-isopentenyloxy-gamma-fagarine, has been used as a precursor for the chemical asymmetric synthesis of the enantiopure alkaloids: evoxine, anhydroevoxine and evodine. The possible roles of oxygenase and other oxygen-atom-transfer enzymes, in the biosynthetic pathways of the C. ternata alkaloids, have been discussed. PMID- 17728866 TI - Host-rotaxanes model proteins that promote ligand association through a favorable change in configurational entropy. AB - Proteins can reduce the entropic penalty for ligand association through a favorable change in configurational entropy. To investigate this process, the Delta G(o), Delta H(o), and DeltaS(o) of complexes formed between host-rotaxanes and guests were determined and compared to discover the relationship between rotaxane-structure and the energies involved in guest-association in water and DMSO. Fluorescence quenching assays provided the association constants. Van't Hoff analysis of variable temperature assays gave the enthalpies of binding. The driving force for the association of a guest and a host-rotaxane can switch from being enthalpically to entropically driven with a change in the solvent or guest. This study shows that a dramatic increase in the entropy of binding can be obtained through the addition of a rotaxane-wheel to a synthetic host. An increased motion of the wheel appears to be the source of the positive binding entropy, which would be an example of favorable configurational entropy promoting complex formation. PMID- 17728867 TI - Rigid-rod anion-pi slides for multiion hopping across lipid bilayers. AB - Shape-persistent oligo-p-phenylene-N,N-naphthalenediimide (O-NDI) rods are introduced as anion-pi slides for chloride-selective multiion hopping across lipid bilayers. Results from end-group engineering and covalent capture as O-NDI hairpins suggested that self-assembly into transmembrane O-NDI bundles is essential for activity. A halide topology VI (Cl > F > Br approximately I, Cl/Br approximately Cl/I > 7) implied strong anion binding along the anion-pi slides with relatively weak contributions from size exclusion (F >or= OAc). Anomalous mole fraction effects (AMFE) supported the occurrence of multiion hopping along the pi-acidic O-NDI rods. The existence of anion-pi interactions was corroborated by high-level ab initio and DFT calculations. The latter revealed positive NDI quadrupole moments far beyond the hexafluorobenzene standard. Computational studies further suggested that anion binding occurs at the confined, pi-acidic edges of the sticky NDI surface and is influenced by the nature of the phenyl spacer between two NDIs. With regard to methods development, a detailed analysis of the detection of ion selectivity with the HPTS assay including AMFE in vesicles is provided. PMID- 17728869 TI - Electrophilicity parameters for 2-benzylidene-indan-1,3-diones--a systematic extension of the benzhydrylium based electrophilicity scale. AB - Kinetics of the reactions of four 2-benzylidene-indan-1,3-diones (1a-d) with carbanions (2a-I) have been studied photometrically in dimethyl sulfoxide solution at 20 degrees C, and the electrophilicity parameters E were determined by the linear free energy relationship log k(2)(20 degrees C) = s(N + E) (eqn (1)). The rate-determining step of these reactions is the nucleophilic attack of the carbon nucleophile at the double bond of the Michael acceptor. Comparisons with literature data show that the linear free energy relationship (eqn (1)) allows the semiquantitative prediction of the reactivities of 2-benzylidene-indan 1,3-diones towards various nucleophiles. PMID- 17728868 TI - A 1-acetamido derivative of 6-epi-valienamine: an inhibitor of a diverse group of beta-N-acetylglucosaminidases. AB - The synthesis of an analogue of 6-epi-valienamine bearing an acetamido group and its characterisation as an inhibitor of beta-N-acetylglucosaminidases are described. The compound is a good inhibitor of both human O-GlcNAcase and human beta-hexosaminidase, as well as two bacterial beta-N-acetylglucosaminidases. A 3 D structure of the complex of Bacteroides thetaiotaomicron BtGH84 with the inhibitor shows the unsaturated ring is surprisingly distorted away from its favoured solution phase conformation and reveals potential for improved inhibitor potency. PMID- 17728870 TI - Studies on the mechanism of the Carr-Price blue colour reaction. AB - The reaction of retinoids (retinol, retinyl acetate and anhydroretinol) with Bronsted acids was studied as a model system for the Carr-Price reaction. The anhydroretinylic cation was characterised by VIS and 2D NMR spectroscopy, including an estimate of the charge distribution and region of bond inversion, observed in a mixture of identified E/Z isomers. Products obtained by quenching with NaOMe-MeOH were identified by HPLC and MS. The classical Carr-Price reaction between retinol (vitamin A) and the Lewis acid SbCl(3) in saturated chloroform solution was reinvestigated by VIS, NMR, EPR, dynamic light scattering and chemical quenching. Whereas product instability and failure to provide informative NMR spectra indicated a radical cation, EPR results excluded free radical species. Dynamic light scattering experiments, in comparison with model systems, revealed strong aggregation for the Carr-Price complex, rationalizing the low stability, NMR problems and dimerisation observed by chemical quenching. The VIS data support structural similarity of the blue Carr-Price product with the delocalized anhydroretinylic cation, and a detailed structure of the antimony complex is evaluated. PMID- 17728871 TI - Pyrazolo[3,4-d]pyrimidine ribonucleosides related to 2-aminoadenosine and isoguanosine: synthesis, deamination and tautomerism. AB - The syntheses and properties of 8-aza-7-deazapurine (pyrazolo[3,4-d]pyrimidine) ribonucleosides related to 2-aminoadenosine and isoguanosine are described. Glycosylation of 8-aza-7-deazapurine-2,6-diamine 5 with 1-O-acetyl-2,3,5-tri-O benzoyl-beta-D-ribofuranose (12) in the presence of BF(3) x Et(2)O as a catalyst gave the N(8) isomer 14 (73%) with a trace amount of the N(9) isomer 13a (4.8%). Under the same reaction conditions, the 7-halogenated 8-aza-7-deazapurine-2,6 diamines 6-8 afforded the thermodynamically more stable N(9) nucleosides 13b-d as the only products (53-70%). Thus, a halogen in position 7 shifts the glycosylation from N(8) to N(9). The 8-aza-7-deazapurine-4,6-diamine ribonucleosides 1a-d were converted to the isoguanosine derivatives 3a-d by diazotization of the 2-amino group. Although compounds 1a,b do not contain a nitrogen at position 7 (the enzyme binding site), they were deaminated by adenosine deaminase; however, their deamination occurred with a much slower velocity than that of the related purines. The pK(a) values indicate that the 7 non-functionalized nucleosides 1a (pK(a) 5.8) and 15 (pK(a) 6.4) are possibly protonated in neutral conditions when incorporated into RNA. The nucleosides 3a-d exist predominantly in the keto (lactam) form with K(TAUT) (keto/enol) values of 400-1200 compared to 10(3)-10(4) for pyrrolo[2,3-d]pyrimidine isoguanosine derivatives 4a-c and 10 for isoguanosine itself, which will reduce RNA mispairing with U. PMID- 17728872 TI - Molecular inclusion of organometallic sandwich complexes within hybrid cavitand resorcin[4]arene receptors. AB - Two different hybrid cavitand-resorcin[4]arenes are shown to be effective and selective receptors for the molecular inclusion of positively charged organometallic sandwich complexes of appropriate size. The binding constants of the 1 : 1 complexes formed with a series of neutral and positively charged metallocenes have been calculated using different titration techniques. The motion of the included metallocene and the kinetics of the complexation process are investigated. The voltammetric behaviour of the inclusion complexes formed with cobaltocenium is also studied. PMID- 17728873 TI - Platinum-catalyzed hydrofunctionalization of unactivated alkenes with carbon, nitrogen and oxygen nucleophiles. AB - The transition metal-catalyzed addition of the X-H bond of a carbon, nitrogen or oxygen nucleophile across the C[double bond]C bond of an unactivated alkene (hydrofunctionalization) represents an attractive, atom-economical approach to the synthesis of carbocyclic and heterocyclic molecules and for the elaboration of ethylene and 1-alkenes. We have developed a family of Pt(II)-catalyzed protocols for the inter- and intramolecular hydrofunctionalization of unactivated alkenes with a range of H-X nucleophiles including beta-diketones, indoles, amines, carboxamides and alcohols. These transformations display good functional group compatibility, low moisture sensitivity, and often good generality. PMID- 17728874 TI - Asymmetric catalysis of metal complexes with non-planar ONNO ligands: salen, salalen and salan. AB - Chiral metal (M)-salen complexes are one of the most versatile asymmetric catalysts and the catalysis of trans-M(salen) complexes has been well cultivated. On the other hand, non-planar cis-beta M(salen) complexes were recently found to show unique asymmetric catalysis that cannot be attained by trans-M(salen) complexes. Moreover, related non-planar M(salalen) and M(salan) complexes were also found to exert unprecedented asymmetric catalysis. This Feature Article summarizes the seminal studies on asymmetric catalysis of non-planar M(ONNO) complexes, full utilization of which will provide marked improvement in asymmetric synthesis. PMID- 17728875 TI - Metal catalyzed rearrangement of a 2,2'-bipyridine Schiff-base ligand to a quaterpyridine-type complex. AB - A Co(II) quaterpyridine-type complex has been prepared via a one-pot transformation of a 2,2'-bipyridine Schiff-base ligand in the presence of a Lewis acidic metal salt. PMID- 17728876 TI - Reactive block copolymer scaffolds. AB - Block copolymers with sequences of differential reactivity were synthesized, and the step-wise and selective derivatization to form a new block copolymer was demonstrated. PMID- 17728877 TI - A small tris(imidazolium) cage forms an N-heterocyclic carbene complex with silver(I). AB - A small, sterically rigid tris(imidazolium) cyclophane reacts with Ag2O to give an Ag(I) carbene complex in which one of the imidazolium moieties remains protonated. PMID- 17728878 TI - A triazine-based three-directional rigid-rod tecton forms a novel 1D channel structure. AB - A large, symmetrically substituted triazine-based molecule, synthesized by a copper-free Sonogashira coupling procedure self-assembles to form a novel 1D channel structure that hosts chlorobenzene molecules as guests. PMID- 17728880 TI - 2D warp-and-woof interwoven networks constructed by helical chains with different chirality. AB - Two unprecedented 2D entangled layers of warp-and-woof threads interwoven by left and right-handed helical chains, {[Mn(salen)Au(CN)2]4(H2O)}n (salen = N,N' ethylenebis(salicylideneaminato)) and {Mn(acacen)Ag(CN)2}n (acacen = N,N' ethylenebis(acetylacetonylideneiminate)) 2, have been synthesized and characterized. PMID- 17728879 TI - A template-based mnemonic for monoamine oxidase (MAO-N) catalyzed reactions and its application to the chemo-enzymatic deracemisation of the alkaloid (+/-) crispine A. AB - A template-based mnemonic has been developed for the enzyme monoamine oxidase from Aspergillus niger and has been used to successfully identify the alkaloid (+/-)-crispine A as a target for chemo-enzymatic deracemisation yielding the biologically active (R)-enantiomer in 97% e.e. PMID- 17728881 TI - Enantioselective hydroxylation of nitroalkenes: an organocatalytic approach. AB - An easy hydroxylation of aliphatic nitroalkenes in high yields and enantioselectivities is catalysed by bifunctional thiourea-cinchona alkaloids giving access to optically active nitroalcohols and aminoalcohols as final products. PMID- 17728882 TI - The Ni2+ binding properties of Helicobacter pylori NikR. AB - The binding constants between Ni2+ and Helicobacterpylori NikR have been determined using isothermal titration microcalorimetry in order to rationalize the role of this protein as a nickel-dependent biological sensor. PMID- 17728883 TI - Concerning the molecular and electronic structure of a tungsten-tungsten quadruply bonded complex supported by two 6-carboethoxy-2-carboxylatoazulene ligands. AB - The preparation and molecular structure of a W2(4+)-quadruply bonded complex is reported wherein two mutually trans azulene-2-carboxylato ligands are shown to be strongly coupled by ligand pi-M2delta-ligand pi conjugation. PMID- 17728885 TI - Redox-active iron-containing polymers: synthesis and anionic polymerization of a C-ferrocenyl-substituted phosphaalkene. AB - The addition polymerization of a ferrocenyl-substituted P[double bond]C bond leads to new redox-active polymers with functional ferrocene and phosphine moieties. PMID- 17728884 TI - Electrochemical synthesis of SnO2 films containing three-dimensionally organized uniform mesopores via interfacial surfactant templating. AB - SnO2 films containing organized mesopores and nanocrystalline frameworks with easily removable surfactant templates were produced electrochemically using interfacial amphiphilic assemblies formed on the working electrode as a template. PMID- 17728886 TI - A stable chiral diaminocyclopropenylidene. AB - The chiral carbene bis[bis(R-1-phenylethyl)amino]cyclopropenylidene 2 and its dicarbene-silver complex [Ag(2)2]BF4 (3) have been isolated in good yields from the reactions of bis[bis(R-1-phenylethyl)amino]cyclopropenylium tetrafluoroborate (1)BF4 with potassium bis(trimethylsilyl)amide or with Ag2O, respectively; the molecular structures of (1)ClO4, 2 and 3 have been determined by X-ray diffraction analyses. PMID- 17728887 TI - Sequential C-F activation and borylation of fluoropyridines via intermediate Rh(I) fluoropyridyl complexes: a multinuclear NMR investigation. AB - The C-F bond activation of fluoropyridines by [Rh(SiPh3)(PMe3)3] afforded Rh(I) fluoropyridyl complexes of the type [Rh(Ar(F))(PMe3)3] with concomitant formation of fluorotriphenylsilane; subsequent treatment with bis-catecholatodiboron yielded fac-[Rh(Bcat)3(PMe3)3] and the free fluoropyridyl boronate esters (Ar(F)Bcat). PMID- 17728888 TI - A novel transmetallation of arylzinc species into arylboronates from aryl halides in a barbier procedure. AB - A variety of functionalized arylboronates are obtained in moderate to excellent yield by a one-step chemical procedure from the corresponding halides and a haloboronic ester via an intermediate arylzinc species. PMID- 17728889 TI - Catalytic synthesis of biodiesel from high free fatty acid-containing feedstocks. AB - Recyclable and reusable heterogeneous diarylammonium catalysts are highly effective in catalyzing the esterification of the free fatty acid (FFA) present in greases to methyl esters to reduce the FFA content from 12-40 wt% to 0.5-1 wt%; the resulting ester-glyceride mixture (pretreated grease) could then be readily converted to methyl esters by base-catalyzed transesterification. PMID- 17728890 TI - Polymer-supported oligosaccharide synthesis using ultrafiltration methodology. AB - Polymer-supported oligosaccharide synthesis was carried out using an ultrafiltration technique in which the synthesized polymer-bound oligosaccharides were separated from the other reagents by ultrafiltration though membranes with specifically sized pores. PMID- 17728891 TI - Optical isomers of N,N'-bis(1-phenylethyl)-2,6-pyridinedicarboxamide coordinated to europium(III) ions as reliable circularly polarized luminescence calibration standards. AB - The synthesis of two optical isomers of N,N'-bis(1-phenylethyl)-2,6 pyridinedicarboxamide and the constant circularly polarized luminescence (CPL) activity of their acetonitrile trivalent europium complex solutions over a long period of time open new perspectives for performing accurate routine CPL calibration tests at low cost. PMID- 17728892 TI - A novel fluorine-metal exchange reaction of pentafluorocrotonate with organocuprate. Generation of beta-metallated tetrafluorocrotonate and its cross coupling reaction. AB - Fluorine-metal exchange reaction of 2,3,4,4,4-pentafluorocrotonates with organocuprate derived from Grignard reagent and CuCN takes place efficiently to generate the beta-metallated tetrafluorocrotonate intermediate, which reacts with various electrophiles to give beta-substituted 2,4,4,4-tetrafluorocrotonates. PMID- 17728894 TI - [Predictors of the level of patient satisfaction in a university hospital]. AB - BACKGROUND: Client satisfaction is an important indicator of the quality of services, and health care is not an exemption. AIM: To explore and establish the predictors that exert the greater influence on the level of satisfaction with the service offered in a University Hospital. MATERIAL AND METHOD: The source of the study is a data base, obtained from a survery made to 355 patients of the Hospital Clinico de la Pontificia Universidad Catolica de Chile prior to discharge. A multiple regression analysis was used to determine the relative importance of the different factors in the quality of service. The regression variables were reduced to a number of factors, obtained of Factorial Analysis and a Varimax rotation, allowing them to clarify their relations. RESULTS: After performing the main components analysis, seven factors or dimensions that explained a 69% of the total variance were obtained. The predictive model explains up to 40% of the criterion variable (Global Satisfaction during the hospitalization). The factor with the greatest predictive power was the relationship between the patients and nursing staff. Other factors that emerged as important were communication, medical attention and room conditions. CONCLUSIONS: Perceptive type components had the greater relative weight to determine the level of patient satisfaction in this survey. PMID- 17728893 TI - [Surgical treatment of gastric cancer: results in 423 cases]. AB - BACKGROUND: Gastric cancer is the second cause of cancer death worldwide and the first cause in Chile. Management of this pathology is controversial. AIM: To report the results on morbidity, mortality, and long-term survival rates of surgical treatment of gastric cancer, and compare them with those reported in the literature. MATERIAL AND METHODS: Follow up of 423 patients (aged 16 to 88 years, 271 males) operated for a gastric adenocarcinoma between 1996 and 2002. Patients were staged with the 5th edition of TNM staging system, and the 2nd edition in English of the Japanese Classification of Gastric Cancer. Morbidity was assessed using the classification of the Memorial Kettering Cancer Center group. Kapplan Meier method was used to assay survival, and Log rank Test to compare long-term survivals. RESULTS: Resectability of the lesions was 70.4%, and 88% of them corresponded to a curative-intended surgery. Seventy percent of patients were in stage TNM IIIA or higher at the moment of surgery. Mortality in curative intended operated patients was 4.2%, and morbidity was 33.7%. Overall five years survival rate was 33%: In the group with curative intended surgery it was 52%. Two years survival rate in the non intended curative group was 3.4%. CONCLUSIONS: The reported incidence of complications in our series is similar to that reported in the literature. Five year survival rates, morbidity and mortality were comparable to those reported abroad. PMID- 17728895 TI - [Role of Azathioprine in steroid resistant non infectious ocular inflammatory diseases]. AB - BACKGROUND: Topical and systemic steroids are the first line of treatment of non infectious inflammatory ocular disease. Immunosuppresants are reserved as a second line treatment. AIM: To evaluate the role of Azathioprine (AZA) as a coadyuvant immunosuppressive treatment for non infectious ocular inflammatory diseases (OIDs) resistant to systemic steroid therapy in a retrospective, noncomparative interventional case series. PATIENTS AND METHODS: Patients using oral Prednisone due to an active or recurrent OID, without clinical response, and not receiving any other immunosuppressive treatment were studied. A standard protocol of oral Prednisone (0.5 mg/kg/ day) and oral AZA (2-3 mg/kg/day) during one year was used. Ocular and systemic monthly evaluations were done including relapse rate, steroid dosage, inflammatory score and visual acuity. RESULTS: Thirty patients (10 male) aged 18-75 years (mean 44 years) were studied. Three had bilateral anterior uveitis, one had pars planitis, four had diffuse uveitis, eight Vogt-Koyanahi-Harada syndrome, three Behget's disease, three necrotizing scleritis and eight had retinochoroidopathy A complete initial response was observed in 26 patients (87%). The time of response was between 1 to 6 months (mean 2.65 months). Seventeen percent of these had a relapse 6 to 12 months after AZA was started. In 61 %, visual acuity improved. The ocular inflammatory score decreased in 86.5%. Eleven patients had mild controlled side effects that did not require discontinuation of AZA. CONCLUSIONS: Combined systemic steroid and oral AZA therapy is safe and effective in controlling steroid resistant non infectious inflammatory ocular diseases. PMID- 17728896 TI - [Gender perspective in health care teaching: a pending task]. AB - BACKGROUND: Gender must be considered in the design and implementation of health policies to safeguard equity and accomplish sanitary objectives. AIM: To identify gender perspective in the curricula of five health care careers in the Universidad Austral de Chile. To identify the situation of women in the teaching profile of such curricula. MATERIAL AND METHODS: An exploratory and descriptive study with a critical reading of the structure of the programs of 217 courses. Revision of official academic registries. RESULTS: Gender is usually not included in the curricula of health care careers. The generic language conceals female academics and students. There was a scarce inclusion of cross sectional issues such as collaborative work, interpersonal and democratic relationship, equity and critical analysis. There were no differences in academic achievements between female and male students. The contractual profile of female academics reproduces the gender inequity of the work market. CONCLUSIONS: The inclusion of gender is a pending task in the training of health care professionals. PMID- 17728897 TI - [Clinical features of 17 patients with familial non medullary thyroid carcinoma]. AB - BACKGROUND: Papillary thyroid carcinoma can have familial aggregation. AIM: To compare retrospectively familial non medullary thyroid carcinoma (FNMTC) with sporadic papillary thyroid carcinoma (PTC). MATERIAL AND METHODS: Retrospective analysis of medical records of patients with thyroid carcinoma. An index case was defined as a subject with the diagnosis of differentiated thyroid carcinoma with one or more first degree relatives with the same type of cancer. Seventeen such patients were identified and were compared with 352 subjects with PTC. RESULTS: The most common affected relatives were sisters. Patients with FNMTC were younger than those with PTC. No differences were observed in gender, single or multiple foci, thyroid capsule involvement, surgical border involvement, number of affected lymph nodes and coexistence of follicular hyperplasia. Patients with FNMTC had smaller tumors and had a nine times more common association with lymphocytic thyroiditis. Five patients with FNMTC had local recurrence during 4.8 years of follow up. CONCLUSIONS: Patients with FNMTC commonly have an associated chronic thyroiditis, are younger and have smaller tumors than patients with PTC. PMID- 17728899 TI - [Bile duct diameter before and 12 years after cholecystectomy]. AB - BACKGROUND: Surgeons and radiologists commonly believe that common bile duct dilates after cholecystectomy. AIM: To measure common bile tract diameter before and 12 years after a cholecystectomy for cholelithiasis. MATERIAL AND METHODS: Prospective study of 85 patients (aged 20 to 71 years, 68 females) subjected to a cholecystectomy and followed for 12 years. AH were asymptomatic and had abdominal ultrasound to measure common bile duct diameter, seven days before and 12 years after the surgical procedure. RESULTS: Common bile duct diameter before and 12 years after surgery was 4.6+0.9 and 5.0+1.8 cm respectively (p=NS) among 69 patients aged inverted exclamation markess than 60 years. The figures for 16 patients aged more than 60 years were 5+0.8 and 6.7+1.9 (p <0.03). CONCLUSIONS: Among patients below 60 years of age there is no significant change in bile duct diameter 12 years after surgery. In subjects over 60 years of age there is a significant increase in this diameter. PMID- 17728898 TI - [Fusion of SPECT with computed tomography or magnetic resonance for the interpretation of abnormal tracer uptake]. AB - BACKGROUND: Interpretation of abnormal foci with high tracer uptake may require morphological correlation. Fusion of functional images obtained by single photon emission computed tomography (SPECT) and anatomical images obtained by computed tomography (CT) or magnetic resonance (RM) allows an integrated comprehension of complementary information. AIM: To demonstrate that SPECT/CT fusion with external markers is useful in clinical practice to clarify the location and pathological meaning of questionable foci. MATERIAL AND METHODS: Thirty four pairs of images from separate equipments (31 SPECT/CT and 3 SPECT/RM) pertaining to 29 patients, were fused. Fifty one foci of abnormal tracer uptake of uncertain pathological meaning were analyzed. These were classified before and after the fusion as probably malignant or probably benign. RESULTS: Seventy percent of patients had a differentiated thyroid carcinoma. The fusion localized 100% of foci. Nine percent had a normal and 26% an abnormal anatomy. Before fusion 82% of foci were classified as potentially malignant. This figure changed to 59% after the fusion (p <0.01). Therefore the suspicion of malignancy was presumptively confirmed in 72% of foci and fusion results would have reached a 27% of incremental diagnostic value in 14 cases that changed of category (11 with differentiated thyroid carcinoma, one with colorectal cancer, one with a nasal Ewing sarcoma and one with a brain tumor). CONCLUSIONS: The fusion of SPECT and CT is useful in selected patients, specially those with differentiated thyroid carcinoma. The fusion of SPECT and RM is also feasible. PMID- 17728900 TI - [Association between glutathione peroxidase levels and clinical manifestations of dengue]. AB - BACKGROUND: Glutathione peroxidase (GP) can be used as a marker of oxidative stress in infectious diseases. AIM: To evaluate the association between the levels of glutathione peroxidase (GP) and the manifestations and complications of dengue. PATIENTS AND METHODS: Between April 2003 and December 2004, 161 patients with dengue were prospectively evaluated. In the first evaluation, within 48 and 96 hours of disease onset, a plasma sample was obtained to measure the GP levels. The association between GP levels, clinical manifestations and complications was evaluated during the follow up. RESULTS: Mean GP values were 1198 U/L (95% confidence interval 1089-1306). Values greater than 1200 U/L were associated with headache, arthralgias and increased heart rate. There was a negative association between GP levels and serum triglycerides. During follow up, patients with GP >1200 U/L had a higher frequency of spontaneous hemorrhages. In a logistic regression analysis arthralgias, fever and increased heart rate, were independently associated with levels >1200 U/L. CONCLUSIONS: GP levels was associated to some of the manifestations of dengue. This finding suggests that the intensity of oxidative stress can influence the clinical presentation of dengue. PMID- 17728901 TI - [Clinical characteristics of children and adolescent hospitalized in a university psychiatric clinic]. AB - BACKGROUND: Five percent of children and adolescents consults in mental health services in one year. Approximately one every ten children has a mental health problem. AIM: To assess clinical and demographic factors of children and adolescents hospitalized by psychiatric cause in a university psychiatric clinic. PATIENTS AND METHODS: Review of medical records of 167 subjects aged 9 to 17 years, 97 women, admitted to a Psychiatric Service in the period 2001-2004. The International Classification of Primary Care (ICPC) manual of the World Organization of National Colleges, Academies and Academic Associations of General Practitioners/Family Physicians (WONCA) was used to classify admission complaints and symptoms and DSMIV to classify psychiatric disorders. RESULTS: Mean hospital stay was 11+8 days. The main admission causes were suicidal attempts and psychomotor agitation/impulsive behavior in 54% and 26% of cases, respectively. The main psychiatric diagnoses were depressive disorder, suicide attempt and bipolar disorder. In 69% of patients, the personality diagnosis was deferred. Only 25% of families were considered functional. CONCLUSIONS: Affective disorders and suicidal behavior are the main psychiatric diagnoses at discharge in children and adolescents admitted to a psychiatric impatient service. PMID- 17728902 TI - [Colitis cystica profunda: report of one case]. AB - Colitis cystica profunda is a benign condition that can be confused with adenocarcinoma. We report a 35 year-old woman that received radiotherapy for a uterine cervical carcinoma who presented intermittent hematochezia three times after ending the therapy. This episode was diagnosed and treated as a radiation colitis and the patient remained asymptomatic for six years. After this period she presented again intermittent hematochezia and a rectal mass that was surgically removed. The pathology report disclosed a colitis cystica profunda. PMID- 17728903 TI - [Requirement of fast ventricular stimulation to induce atrio ventricular nodal tachycardia: report of one case]. AB - We report a 59 year-old woman who had recurrent episodes of paroxystic supraventricular tachycardia despite pharmacologic therapy. A previous electrophysiological study (EPS) was done two years earlier without induction of any sustained arrhythmia. A new EPS was performed, during which atrial and ventricular programmed stimulation failed to induce tachycardia, and only by fast ventricular stimulation during intravenous isoproterenol infusion, a typical atrio ventricular nodal reentrant tachycardia (AVNRT) was induced. We successfully ablated the slow nodal pathway. After ablation the tachycardia was not inducible. We comment the occasional difficulties to induce AVNRT and the importance of a complete induction protocol to avoid false negative studies during the EPS. PMID- 17728904 TI - [Hepatocarcinoma with sarcomatoid transformation: case report]. AB - Hepatocarcinoma with sarcomatoid transformation is uncommon. It presents clinically with inverted exclamation markeucocytosis and fever, resembling a liver abscess. We report a 40 year-old male that presented pain in the right upper quadrant and fever. Abdominal imaging showed an hypodense image in the liver that resembled a liver abscess. The patient was subjected to a percutaneous drainage obtaining 150 ml of an hemorrhagic fluid whose culture was negative. The clinical picture persisted and the patient was subjected to a right hepatectomy. The pathological study of the surgical piece disclosed a hepatocarcinoma with sarcomatoid transformation. The patient was discharged sixteen days after surgery. PMID- 17728906 TI - [Coverage of preventive health activities in a Chilean region, calculated using the preventive medicine index]. AB - BACKGROUND: Preventive activities of the public health system in Chile are not integrated and there is no parameter assessing the whole population that is benefited with these activities. AIM: To develop and implement a mathematical measure of the coverage of preventive health activities, provided to different age groups. MATERIAL AND METHODS: Data was gathered from the monthly statistical reports of the women, children, teenager, adult and elderly health programs in 30 communities of the Seventh Chilean Region. The preventive medicine index (PMI) was calculated as the ratio between the population that was ascribed to each program and the population that was a potential beneficiary of such program. RESULTS: In the studied region, the global coverage of preventive medicine, calculated using the PMI, increased from 0.229 in 1999 to 0.370 in 2003. This represents a 61% increment. However, there are important inequalities in the access to preventive health in the different communities of the region. CONCLUSIONS: The PMI revealed a substantial increment in preventive health activities in the studied region. PMID- 17728905 TI - [Aripiprazole for the treatment of Tourette syndrome. Experience in 10 patients]. AB - BACKGROUND: Tourette syndrome is a neuropsychiatric disorder characterized by motor and vocal tics, attentional deficit, poor control of impulses and obsessive compulsive disorder. Pharmacological treatment is often disappointing due to partial response and frequent poor tolerance to neuroleptic drugs which are otherwise the most effective therapy so far. AIM: To report a lasting improvement obtained with a new drug, aripiprazole that acts modulating both dopaminergic and serotoninergic neurotransmission. MATERIAL AND METHODS: Ten patients refractory to their usual therapy, aged 10 to 35 years, were switched to aripiprazole in an open trial. RESULTS: Nine of the 10 patients showed a significant response assessed by the Yale severity tics rating scale and the clinical global impression scale (p <0.01). No relevant adverse effects were observed. CONCLUSIONS: Aripiprazole may be a good pharmacological option for patients with Tourette syndrome. PMID- 17728907 TI - [Therapeutical targets for revert liver fibrosis]. AB - Liver fibrosis is the common response to chronic liver injury, ultimately leading to cirrhosis and its complications: portal hypertension, liver failure, hepatic encephalopathy, and hepatocellular carcinoma and others. Efficient and well tolerated antifibrotic drugs are still lacking, and current treatment of hepatic fibrosis is limited to withdrawal of the noxious agent. Efforts over the past decade have mainly focused on fibrogenic cells generating the scarring response, although promising data on inhibition of parenchymal injury or reduction of liver inflammation have also been obtained. A large number of approaches have been validated in culture studies and in animal models, and several clinical trials are underway or anticipated for a growing number of molecules. This review highlight recent advances in the molecular mechanisms of liver fibrosis and discusses mechanistically based strategies that have recently emerged. PMID- 17728908 TI - [Genotype-by-nutrition interaction: interpretation of epidemiological studies]. AB - EpidemiologicaL methods are increasingly used to assess the role of genetic factors and their interaction with environmental factors, in the occurrence of diseases in populations. Nutrition is one of the most relevant components of the interaction between the human being and the environment. Therefore, the interaction between susceptibility genotypes and nutritional risk factors has a great importance in the study of several chronic diseases. The aim of this article is to review different epidemiologic study designs and basic methods of analysis commonly used in the evaluation of the interaction between nutritional and genetic factors. These study designs and analytical methods are equally valid for the assessment of genotype-environment or genotype-genotype interaction. PMID- 17728909 TI - [Medicine between two sets of values: the Biblical Ethics and human or modern ethics]. AB - In this article, the author -a Bishop of the Catholic Church-discusses the similarities and differences between two sets of ethical values that may guide the behaviour of medical professionals towards their patients and society. One set derives from Biblical principles contained in the Old and New Testaments, mainly represented by the Ten Commandments and Christ's Prayer from the Mountain. These principles are shared by all Christian nominations and by the Jewish and Muslim religions. The second one, although intrinsically agnostic, is also focused in the human individual and the human society. Both streams obey a "natural morality" common to all humans: every individual should respect each one's conscience, should avoid doing to others what each one would not inverted exclamation markike to receive, to do not lie, kill or rob, to obey the rules of family and society. The Biblical Ethics stresses the value of responsibility in human behaviour while Modern Ethics sets the point in authenticity. In spite of their differences, the sharing of crucial points and end goals should inspire medical professionals regardless their religious beliefs to follow a common set of ethical values and to remain united in pursuing it. PMID- 17728910 TI - [Services for the care and prevention of birth defects. Reduced report of a World Health Organization and March of Dimes Foundation meeting]. AB - On 17-19 May 2006, the World Health Organization (WHO) and the March of Dimes Birth Defects Foundation held a meeting in Geneva: The Management of Birth Defects and Haemoglobin Disorders. Meeting participants included 18 experts from developing and industrialized countries, including the author and nine staff from WHO Headquarters. The meeting had five goals: (A) ratify the data on the global toll of birth defects presented in the MOD Global Report; (B) agree upon a definition of terms; (C) develop a collaborative plan for strengthening care and prevention of birth defects; (D) develop a plan for strengthening care and prevention of haemoglobin disorders; and (E) determine how potential stakeholders could contribute to these efforts. The consensus for each of the goals were: a) Participants endorsed the estimates in the MOD Global Report, b) Participants concluded that the term "birth defect" is synonymous with the term "congenital disorder", whereas the term "congenital anomalies" should be avoided, c) Participants agreed that 70% of birth defects could be prevented, ameliorated or treated effectively, by the strengthening of medical genetic services, d) Participants agreed that efforts must be made to improve the control of hemoglobin disorders in developing countries, and e) Progress will require the combined efforts and political will of the WHO. PMID- 17728913 TI - [Microbiologic and molecular diagnostic of cariogenic bacteria in pregnant women from the Araucania Region of Chile]. AB - Dental caries is a transmissible infectious disease in which Streptococcus mutans is a principal protagonist. Although it is widely believed that pregnancy is harmful to teeth, the effect of pregnancy on the development of caries is not clear. Considering this situation, the aim of the present study was to evaluate the levels of infection and to differentiate bacterial species with cariogenic potential in pregnant women from the Araucania region in Chile, by bacteriological and molecular analysis. In this work, we evaluated 51 pregnant women aged 15 to 40 years. The results show that 100% of women are infected by mutans streptococci Group, and 70.6% exhibited high levels of infection (> 500.000 cfu/mL). The molecular analysis shows that Streptococcus mutans and Streptococcus sobrinus frequencies were 92.1% and 1.9%, respectively. In conclusion, our data suggest that pregnant women are a high risk group for caries development. PMID- 17728912 TI - [Impact of infectious diseases specialist evaluation on the rational use of antibiotics in patients with Streptococcus pneumoniae bacteremia]. AB - The increasing reporting of Streptococcus pneumoniae resistance to penicillin has lead to the recommendation of third generation cephalospirins for the treatment of serious pneumococcal infections. As a consequence, clinicians usually do not prescribe first line antibiotics despiste the availability of susceptibility studies. Whit the aim to evaluate the impact of the infectious diseases specialist evaluation in the apropriate use oh the susceptibility studies, two series were compared: a historic control one (1998-2002, n = 50) and a prospectuve group that had the advisement of one infectious diseases specialist (2003-2006, n = 60). In both series, pneumonia stood out as the source of the bacteremia, and -alcoholism/hepatic insufficiency as associated factor. In the first series, 48 isolates resulted susceptible to penicillin by agar diffusion, and 1 out of 36 patients with pneumonia had a change in the antibiotic therapy to penicillin. In the prospective series, we found 56 susceptible isolates, and the remaining four were classified as intermediate susceptibility according to the MIC value. Antibiotics were changed in 36 out of 50 patients with bacteremic pneumococcal pneumonia (p < 0.05). The infectious diseases specialist evaluation had a positive impact on the use of the microbiological information for therapeutics purposes. PMID- 17728914 TI - [Human immunodeficiency virus infection in infancy]. AB - This paper describes the increasing trends and changing patterns of human immunodeficiency virus (HIV) infection in children occurring since 1982-83 when the first cases were reported worldwide and from 1987-89 when the first cases were detected in Chile. Advances and obstacles dealing with pediatric HIV in Chile are discussed. The most relevant advance is the outstanding reduction in vertical transmission of HIV associated with the implementation of preventive strategies. Risk of vertical transmission has decreased from 35%o in absence of preventive strategies to 2%o with prevention that include maternal and newborn antiretroviral therapy, elective caesarean section and replacement of breast feeding by artificial milk. The main obstacle to further reduce cases has been the delay in implementation of universal screening for pregnant women. This delay has resulted in that currently, the great majority of pediatric HIV cases are detected among symptomatic children. We propose a guideline to detect and appropriately derive pregnant women infected with HIV and children exposed or infected with the virus in order to further reduce the number of children with AIDS in Chile. PMID- 17728916 TI - [LA TRAVIATA: La camelia de Verdi]. PMID- 17728915 TI - [Ocular tuberculosis]. AB - Tuberculosis (TB) is considered a public health problem in several countries. This disease is classified as either pulmonary or extrapulmonary. Within the extrapulmonary disease, ocular involvement is uncommon but it is important to recognize it because its incidence has been reported up to 1%. Ocular TB cases can be divided in primary and secondary. These manifestations can be caused by an active infection that invades the eye or by an immunologic reaction of delayed hypersensitivity in absence of the infectious agent. The most common clinical presentations are: chronic anterior uveitis, choroiditis and sclerokeratitis. Despite the existence of highly sensitive molecular diagnostic techniques, the diagnosis of ocular tuberculosis continues to be presumptive, based upon clinical presentation, systemic evaluation and response to treatment. For the treatment we use four drugs during a two month period (isoniazid, rifampin, pyrazinamide and ethambutol) and two drugs for four additional months. PMID- 17728917 TI - [Acute otitis media: Diagnosis and treatment]. AB - Acute otitis media (AOM) is one of the most common causes of medical visit and antimicrobial use in children. A rationale management approach requires a thorough clinical exam and updated knowledge on local patterns of microorganisms involved and antimicrobial susceptibility profiles. Clinical diagnosis should be performed with pneumatic otoscopy. The most common microorganism causing AOM in Santiago, Chile according to local studies are Streptococcus pneumoniae (40%o), non-capsulated Haemophilus influenzae (29%), Streptococcus pyogenes (7%) and Moraxella catarrhalis (4%). S. pneumoniae has acquired resistance to penicillin in the last decade, resistance that has been extrapolated to other (b lactams such as amoxicillin, reason why broader spectrum antimicrobials are routinely prescribed. Clinical practice has consistently shown although that the great majority of children receiving amoxicillin at a dose of 80-100 mg/kg/day resolve their AOM. Recent studies from our group have demonstrated that resistance to penicillin can not be extrapolated to amoxicillin. In vitro high level resistance to penicillin vs amoxicillin is 18%> vs 0.5%. Based on this data, our current recommendation for AOM is amoxicillin 80 mg/kg/day, q 12 hours for 10 days in infants and for 5-7 days in children > 2 years of age who have not had an episode within the previous month. For amoxicillin failures, amoxicillin + (b lactam inhibitor or a second generation cephalosporin are recommended, especially in areas with a high prevalence of (b lactam producing H. influenzae and M. catarrhalis. Treatment of children with AOM universally require appropriate follow-up in order to comply with the proposed algorithm. PMID- 17728918 TI - [Pulmonary complications in children with human immunodeficiency virus infection]. AB - Pulmonary complications in children infected by human immunodeficiency virus (HIV) are common and may be the first manifestation of acquired immunodeficiency syndrome (AIDS). The aim of our study was to review pulmonary diseases and complications in pediatric patients with HIV infection in a large tertiary hospital in Santiago, Chile. We performed a retrospective, descriptive analysis of 17 patients with HIV infection controlled at the Hospital Dr. Sotero del Rio. Respiratory complications/diseases were: overall pneumonia (n: 14), recurrent pneumonia (n: 10), citomegalovirus associated pneumonia (n: 4), Pneumocystis jiroveci associated pneumonia (n: 1) pulmonary tuberculosis (n: 1), lymphoid interstitial pneumonia (n: 3) and chronic pulmonary disease (n: 7). Microorganisms isolated were mostly atypical and frequently associated with severe and chronic pulmonary damage. A high degree of suspicion is required to detect atypical microorganisms promptly, in order to rapidly implement pathogen targeted therapy that could potentially decrease the possibility of sequelae. PMID- 17728919 TI - [An outbreak of scabies in a tertiary-care hospital from a crusted scabies case]. AB - In February 2005 we performed an epidemiological study of an outbreak of scabies in a tertiary-care hospital which started from a crusted scabies case. We detected 10 secondary cases, 8 in healthcare workers and 2 in hospitalized patients. The attack rate was 4.1%. In contrast to previously described outbreaks, the crusted scabies case was recognized at admission. The outbreak causes were: lacking adherence to contact precautions, long stay of the primary case in the hospital ward and delay of specific treatment. The main control measures were: alerting the hospital services about the outbreak, performing epidemiologic surveillance, coordinating with the Hospital Direction and the Occupational Health Department, education of healthcare workers in control measures, implementation of isolation measures and treatment of cases and contacts with 5% permethrin topical lotion. PMID- 17728920 TI - [Enterococcus sp. Part two]. PMID- 17728921 TI - [Apnea as a presenting symptom in human metapneumovirus infection]. AB - Human metapneumovirus (hMPV), a recently described pathogen of lower respiratory tract infections (LRTI), has been detected in 5,4% of Chilean infants hospitalized for LRTI whom are negative for adenovirus, respiratory syncytial virus, influenza and parainfluenza viruses. hMPV may cause bronchiolitis or pneumonia in hospitalized patients, and ocassionally require admission to intensive care units and mechanical ventilation. The infection has been associated with apnea, especially in preterm infants. Nosocomial dissemination has also been described. We present the case of a one-month-of age premature infant with apnea, and infection caused by hMPV of probable nosocomial aquisition. Clinical features of hMPV infection are reviewed and its association with apnea and nosocomial transmission is discussed. hMPV should be included in the routine diagnosis of respiratory viruses in infants with apnea and should be considered among the respiratory pathogens associated with nosocomial transmission. PMID- 17728922 TI - [Fatal necrotizing fasciitis due to Serratia marcescens]. AB - An 81 year old female patient with chronic heart failure and atrial fibrillation receiving anticoagulant therapy, was admitted with progressive pain on her right leg for the past 24 hours, associated to local erythema, edema and warmth. The lesion evolved at the same site where she presented a chronic ulcer for the previous 5 months managed only with local care. At admission a necrotic plaque on the affected site was perceived; there was no hypotension or mental confusion but signs of a deep venous thrombosis on the involved leg were found. She was febrile (37.8 degrees C) and with tachychardia (126 per minute). Laboratory evaluation revealed normal white blood cell count and a subtherapheutic anticoagulant INR value. A chest x-ray showed infiltrates on the left lower lung lobe. On the following hours the lesion evolved with increasing pain, haemorrhagic bullae and a purulent discharge through the ulcer, with the patient developing mental deterioration, hypotension, respiratory failure and shock. The patient received intravenous ciprofloxacin and clindamycin and was operated 15 hours after admission performing an over-the knee amputation. A cardiac catheterization demonstrated a low cardiac output (2.3 L/min), and both a high systemic vascular resistance (2888 din.s.cm(-5)) and pulmonary capillary wedge pressure (17 cm H(2)0), results compatible with cardiogenic shock. Evolution was progressively worse and she died of multiple organic failure 36 hours after admission. Two blood culture samples grew Serratia marcescens. No necropsy was performed and cultures taken from the leg remained negative. PMID- 17728923 TI - [Acute retinal necrosis in an acute leukemia pediatric patient]. AB - Acute retinal necrosis (ARN) is a serious condition that can impair vision. It mostly occurs in adult patients, especially those severely immunocompromised, in association with a reactivation of a herpes virus infection. We present a 4 years old patient with high risk acute leukemia, whom during a course of intense chemotherapy acquired chickenpox with visceral involvement that affected the retina, causing unilateral blindness. Varicella-zoster virus was detected by PCR in the vitreous humor, in spite of previous acyclovir treatment. The contralateral vision remained undamaged. PMID- 17728924 TI - [Acute retinal necrosis: an adult disease visits pediatrics]. AB - Acute retinal necrosis (ARN) is a serious condition that can impair vision. It mostly occurs in adult patients, especially those severely immunocompromised, in association with a reactivation of a herpes virus infection. Clinical and ophtalmological features of ARN and recommended diagnostic and management strategies are reviewed. PMID- 17728925 TI - [John Snow, the cholera epidemic and the foundation of modern epidemiology]. AB - John Snow (1813-1858) was a brilliant British physician. Since young he stood out for his acute observation capacity, logical thinking and perseverance, first in anesthetics and later in epidemiology. The successive outbreaks of cholera that affected London, motivated him to study this disease from a populational point of view. He related the appearance of cases to the consumption of "morbid matter", responsible for the acute diarrhea with dehydration that characterizes this disease. Bravely, Snow opposed to certain theories present at his time, sacrificing his own prestige. He was a pioneer in the use of modern epidemiological investigation methodologies such as conducting surveys and spatial epidemiology. Fairly, he is considered nowadays as father of modern epidemiology by the scientific community. PMID- 17728927 TI - Patterns of light interference produced by damaged cuticle cells in human hair. AB - Colorful patterns of light interference have been observed to occur in human hair cuticle cells. The light interference phenomenon has been analyzed by optical microscopy. The strong patterns of light interference appeared only in cuticle cells that had been damaged either mechanically or by thermal stresses. Cuticle cells that were not damaged did not produce this phenomenon. The zones of light interference on the hair surface were seen to extend to cuticle sheath areas whose damage was not apparent when analyzed under the Scanning Electron Microscope. The presence of oils and other hydrophobic materials in the hair had a strong effect in the appearance or disappearance of the interference patterns. PMID- 17728928 TI - Formation of nanostructure on hair surface: its characteristic optical properties and application to hair care products. AB - Uneven structures on hair fiber surface, such as lift up of cuticle or build up of hair spray ingredients, generally cause a diffuse reflection which results in a dull and unhealthy appearance. However, in the case of finer structure than wavelength of visible light, the optical properties change significantly. An application of the phenomenon to hair care products is reported in this paper. Formation of the fine structure on hair surface was achieved by only a shampoo and rinse-off conditioner system including amino-silicone. Chroma enhancement of hair and light introduction into hair fibers were observed simultaneously with formation of the fine structure on the hair surface. The light introduction phenomenon is understood in terms of "Effective Medium Approximation" (EMA). The simulation study based on EMA indicates that a very low refractive index surface is expected to be realized, which well explains the optical experimental results. When the shampoo and conditioner system developed to form the structure on fiber surface was applied to dyed hair, enhancement and long-lasting of vivid appearance was confirmed in spite of dye elution. PMID- 17728929 TI - Diffraction of light by the cuticle structure of hair. AB - Under a microscope, hair looks like a surface relief grating with an irregular sawtooth profile. Using scalar diffraction theory, we model what has been, until now, assumed to be a specular peak in the light scattering data. Diffraction efficiencies are calculated as a function of cuticle thickness. Convolution with apertures and Gaussian processes yields a picture that is consistent with the observed position and structure of the "specular" peak. When the cuticle thickness fails to satisfy the blaze condition, the scattered light is distributed amongst multiple diffraction orders giving rise to a complex central structure. PMID- 17728930 TI - Three-dimensional imaging and analysis of the surface of hair fibers using scanning electron microscopy. PMID- 17728931 TI - Fundamental DSC investigations of alpha-keratinous materials as basis for the interpretation of specific effects of chemical, cosmetic treatments on human hair. AB - Alpha-keratinous materials can be considered as two-phase, filament/matrix composites, in which partly crystalline, alpha-helical intermediate filaments (if) are embedded in an amorphous matrix of IF-associated proteins (IFAP). Differential Scanning Calorimetry (DSC) of keratins in water was found to be especially suited to analyze various aspects of the thermal stability of these main morphological components. Results and considerations are reviewed, which were gained by applying the principles derived from fundamental investigations to the specific effects of oxidation (bleaching) and reduction (perm-waving). Properties and interactions of the main morphological components of human hair are considered that are specifically related to the various aspects of their thermal stability. The overall view of the results shows that the course of the thermal unfolding of the alpha-helix in the IFs is independent of the chemical history of hair. The matrix properties are the primary factor controlling the kinetics of the onset of the denaturation process in the IF/IFAP-composite. PMID- 17728932 TI - Investigations of cosmetic treatments on high-pressure differential scanning calorimetry. AB - High Pressure Differential Scanning Calorimetry (HPDSC) can be used to gain information on both the degree of crystallinity in the intermediate filaments (IFs) and the structural rigidity of the surrounding matrix or intermediate filament associated proteins (IFAP) of the hair cortex. We have used HPDSC to measure changes in denaturation temperature (T(D)) and enthalpy (deltaH(D)) of the crystalline components after treatment with bleach products. Literature reports suggest that a decrease in peak denaturation temperature is indicative of permanent damage to the hair. However, changing the rigidity of the matrix surrounding the IFs, by temporarily changing electrostatic interactions, should also result in a similar decrease in peak temperature. The complex nature of bleach formulations including oxidants, alkalizers and salts suggests that several of the components could have a non-permanent affect on salt bridges and hydrogen bonds and hence rigidity or viscosity of the matrix. We have compared the denaturation temperature with levels of lightening (dL) and tensile properties of the fiber after treatment both before and after removal of actives from the fiber. It is evident that the HPDSC results are strongly influenced by formulation components and that these changes are reversible with extensive washing or dialysis. Combined with tensile data, it is proposed that a decrease in T(D) and deltaH(D) following treatment with bleach products can be due to both permanent and reversible changes to either the intermediate filaments or intermediate filament associated proteins of the hair fiber. PMID- 17728933 TI - The effect of treatments on the shear modulus of human hair measured by the single fiber torsion pendulum. AB - Previous studies with the single fiber torsion pendulum have alluded to the ability of this device to selectively measure different regions of a fiber, namely, the core and the sheath. This selective ability of the torsion pendulum was explored further as a means of better understanding treatments effects. First, a substantial reduction in shear modulus was caused by simply abrading the hair fiber surface to remove the cuticle layer. In another experiment, bleaching was found to have a softening effect on the cuticle layer since the shear modulus was reduced significantly. Next, the fibers were subsequently treated with either Polyquaternium-10 or cetyl trimethylammonium bromide (CETAB) and measured again. The CETAB treatment resulted in an increase in the shear modulus indicating fortification of the cuticle layer. Polyquaternium-10 treatment increased the shear modulus slightly. These different effects are explained by the molecular sizes of these compounds-CETAB is a small molecule which can penetrate into the cuticle layer while Polyquaternium-10 is too large to do so. Lastly, the effect of moisture was evaluated by varying the humidity inside a chamber surrounding the sample mounted in the torsion pendulum. This showed a substantial inverse relationship between humidity level and shear modulus that was much more pronounced for bleached hair fibers than for untreated. PMID- 17728934 TI - Peptide structure: Its effect on penetration into human hair. AB - The influence of the peptide structure on its penetration inside hair was studied, together with the effect of hair bleaching (oxidation). For that reason, the outcome of positioning a charged sequence (KAKAK) either at the N or C terminal on hair penetration has been studied for peptides with 17 residues each. It was observed that the penetration of these peptides into hair was driven by electrostatic interactions, where the position of the charged group at the peptide structure was of major importance. The penetration was only achieved for damaged hair due to its higher negative charge at the membrane surface. It was also observed that the peptides were able to restore the original tensile strength of bleached hair. Consequently, the knowledge of hair surface properties is of extreme importance when designing peptides directed for hair treatment. PMID- 17728935 TI - Hair and amino acids: the interactions and the effects. AB - The interaction and the function of some amino acids in hair care applications are discussed. When amino acids are applied to hair in the form of simple aqueous solution, uptake of the amino acids is mainly controlled by ionic equilibrium. When amino acids were incorporated in a hair conditioner, the result was quite different, suggesting the importance of interaction between the amino acids and the cationic surfactants. Uptake of pyrrolidone carboxylic acid (PCA), a derivative of glutamic acid, is enhanced by combining with arginine, an amino with strong affinity towards hair. Effects of some amino acids on bleached/dyed hair are described. A hair conditioner incorporated with alanine improves hair surface hydrophobicity of bleach-damaged hair. Histidine and phenylalanine improve tensile strength. PCA was proved to be effective to improve color retention of dyed hair. PMID- 17728936 TI - Hair medulla morphology and mechanical properties. AB - The morphology of human hair was extensively discussed in the last century, except for hair medulla, mainly because it was believed to have little or no influence on any useful hair property. Early SEM results showed that medulla is formed by unorganized fibrilar material that could be macrofibrils randomly located in the fiber center. The present paper aims to correlate the fibrilar structures with the macrofibrils using transmission electron microscopy (TEM) and to evaluate the influence of medulla on the mechanical properties of hair. TEM micrographs show that the interface between cortex and medulla is surrounded by a CMC layer and that there is less electronically dense material between cortical cells. Cortical cells in medulla give the usual microfibril crystalline arrangement. The cells become scarce and less organized in the center of the medulla, which also shows air filled granules. Average values of the mechanical properties are similar for unmedullated and medullated fibers. However higher dispersion in data for medullated fibers is observed. Unmedulated fibers are more uniform and show smaller diameters. These data indicate that the air cavities in medulla do not interfere with the mechanical properties, but leave hair strength less uniform. PMID- 17728937 TI - Can a topical scalp treatment reduce hair bulb extraction? AB - Generally speaking, when people talk about "hair breakage" they are typically referring to the idea that as they comb or brush their hair, the fibers are elongating and snapping at some weak point in the fiber length. It is well established that as people chemically treat their hair, the keratin proteins are degraded further and the hair become more brittle and susceptible to breakage. For the consumer, hair breakage is registered as hair fibers noted in their comb or brush, and in the drain that they see after a cosmetic treatment. However, a fundamental question that needs to be asked is whether or not the hairs that are seen in the drain are really the result of hair breakage (i.e., a fiber snapping) or are they the result of hairs that are actually being extracted from the scalp by their root bulbs. If the bulk of the hair fibers are actually extracted by the bulb, than it seems somewhat superfluous to try and improve hair strength by improving the exterior of the fiber. The fiber is dead and topical treatments can only smooth, and possibly moisten already established fiber structure and integrity. This paper will attempt to address hair strength by looking at the scalp and follicle as the target for treatment, showing that topical application of a product containing a blend of well-known skin active ingredients can demonstrate potential reductions in hair extractions. An in vivo testing protocol in which 15 voluntary participants with at least 12" hair length were professionally shampooed, and then treated, half-head, with a commercial conditioner, or the same conditioner that contained 5% of a mixture of yeast peptides, fruit acids and green tea polyphenols every day for five days will be discussed. At the beginning and end of the treatment period, the number of hairs that either broke along the fiber, or extracted by the bulb were gathered, separated and counted for both the treated and untreated side of the head. The results of this one-week study demonstrate that the number of hairs that actually break pales in comparison to the number of hairs that are extracted complete with intact root bulb from the follicle. PMID- 17728938 TI - High throughput workflow for coacervate formation and characterization in shampoo systems. AB - Cationic cellulosic polymers find wide utility as benefit agents in shampoo. Deposition of these polymers onto hair has been shown to mend split-ends, improve appearance and wet combing, as well as provide controlled delivery of insoluble actives. The deposition is thought to be enhanced by the formation of a polymer/surfactant complex that phase-separates from the bulk solution upon dilution. A standard characterization method has been developed to characterize the coacervate formation upon dilution, but the test is time and material prohibitive. We have developed a semi-automated high throughput workflow to characterize the coacervate-forming behavior of different shampoo formulations. A procedure that allows testing of real use shampoo dilutions without first formulating a complete shampoo was identified. This procedure was adapted to a Tecan liquid handler by optimizing the parameters for liquid dispensing as well as for mixing. The high throughput workflow enabled preparation and testing of hundreds of formulations with different types and levels of cationic cellulosic polymers and surfactants, and for each formulation a haze diagram was constructed. Optimal formulations and their dilutions that give substantial coacervate formation (determined by haze measurements) were identified. Results from this high throughput workflow were shown to reproduce standard haze and bench-top turbidity measurements, and this workflow has the advantages of using less material and allowing more variables to be tested with significant time savings. PMID- 17728939 TI - Hair melanin content and photodamage. AB - The aim of this study was to compare the susceptibility of hair with different melanin content (virgin white, blond and dark-brown) to photodegradation, evaluating changes on hair color and mechanical properties. Light exposure was carried out with a mercury-vapor lamp for up to 1800h. It was observed that color changes are different for each hair type and dependent on the wavelength range. Breaking elongation and breaking strength were affected in all hair types, mainly by UVB radiation. Results show that the melanin type and content of each hair is not the only parameter related to hair damages caused by sun exposure. PMID- 17728940 TI - Evaluation of hair humidity resistance/moisturization from hair elasticity. AB - Average water regain and hair elasticity (Young's modulus) of virgin dark brown and bleached hair fibers under different relative humidity (RH) were determined. It is observed that hair water regain increases linearly with an increase in RH in the range of 40-85%; and the remaining percent of hair elasticity decreases linearly with an increase in RH in the range of 50-80%. Therefore, measurements of average hair elasticity at 50% and 80% RH, respectively, under various equilibrium times before and after cosmetic treatments can be used to evaluate effects of cosmetic treatments on water adsorption behavior of hair-improvement in hair humidity resistance or enhancement in hair moisture uptake. A Hair Humidity Resistance Factor (H(2)RF) has been defined. If R(2)HF > 1, the product improves hair humidity resistance-anti-frizz; if R(2)HF < 1, the product enhances hair water adsorption; when R(2)HF approximately 1, the product has no significant effect on hair water adsorption behavior. This method was applied to evaluate anti-frizz performance of several shampoo formulations containing Polyquaternium-10, or Polyquaternium-70, or Polyquaternium-67, or Guar Hydroxypropyltrimonium Chloride. It was found PQ-70 shampoo showed the highest H(2)RF value and the best anti-frizz performance among these tested shampoos. The results were consistent with those obtained from Image Analysis. PMID- 17728941 TI - New keratin isolates: actives for natural hair protection. AB - Hair is primarily composed of keratin proteins and it is well established that peptides and proteins bestow desirable effects on the hair, for example improving moisturization and softness. In the present work we describe how keratin actives with unique properties convey a range of beneficial properties to a variety of hair types. It has been observed that these functional keratins protect hair from damage associated with chemical treatments such as perming and relaxation, help to restore the mechanical strength of damaged fibers and decrease fading of colored hair. PMID- 17728942 TI - A cosmetic ingredient innovation for the stabilization and delivery of volatile fluoroether with cosmetic applications. AB - Initially this work attempts to support, evaluate and identify the stabilization and release mechanism of volatile fluoroether (Cosmetic Fluid CF-61) in a self assembling nanostructure in an external water phase (Phoenomulse CE-1) through evaporation rate analysis. The release mechanism is hypothesized to be a result of a dehydration process, a decrease in water efficiency due to evaporation of external water at the liquid-air interface, which results in destabilization of the nanostructure. This work further attempts to quantify the release mechanism of the same volatile fluoroether (Cosmetic Fluid CF-61) from the nanostructure in cosmetic formulations through a newly developed in vitro test method which measures initial foam generation rate. Finally, this work demonstrates the application of these newly developed test methods as a useful tool for product development, formulation navigation, and performance optimization. PMID- 17728943 TI - New high-charge density hydrophobically modified cationic HEC polymers for improved co-deposition of benefit agents and serious conditioning for problem hair. AB - A series of new high charge density Polyquaternium-67(1) (PQ-67) polymers have been prepared and evaluated in shampoo formulations. These new compositions represent an addition to the family of high-viscosity quaternized hydroxyethylcellulose (HEC) polymers with cationic substitution of trimethyl ammonium and dimethyldodecyl ammonium(2) (Figure 1A) described in (1) and (2). The evaluation protocol included objective lab methods and subjective panel studies on different hair types. Commercial conditioning polymers: PQ-67 (Polymers SoftCAT(3)) and cationic guar(4) (Jaguar C-13S(R)(5)) were used as performance benchmarks. It was found that increasing the cationic charge density of the PQ-67 polymers above 1.45 meq/g (equivalent of 2 weight-percent (wt.%) nitrogen) resulted in a several-fold boost of their co-deposition ability. These experimental, high charge density PQ-67 polymers were shown to deliver silicones and other performance ingredients from shampoo formulations more efficiently than any other polymer currently available on the market for rinse-off hair cleansing/conditioning applications. The polymers also provided improved wet and/or dry conditioning, volume control, and could be instrumental in achieving sleek looking hair and improved control/manageability of unruly or frizzy hair. The high charge density PQ-67 polymers are also ideally suited for highly fragranced surfactant-based formulas that are used in aromatherapy and spa products due to their superior ability to deliver fragrance. PMID- 17728944 TI - Hydrolyzed protein derivatives accompanied with synergy by silylation or siliconizing. AB - Effects on hair, of a newly developed hybrid polymer consisting of hydrolyzed protein, modified with an alkyl chain and silicone was investigated. And it was confirmed that the polymer had color retention effect on dyed hair, and good substantivity contributing to hair luster, manageability, moist feel, smoothness and good combability. The above effects were displayed, especially on damaged hair. PMID- 17728945 TI - Determination of the substantivity of emollients to human hair. AB - The determination of silicones and hydrogenated didecenes deposited on human hair from shampoo applications is described. For silicones, induced coupled plasma optical emission spectroscopy (ICP-OES) of extracts and X-ray fluorescence analysis (XRF) of hair strands without any further sample preparation have been applied. Three shampoos from the European and Asian markets have been investigated at repeated shampoo applications followed by the determination of the removability with sodium laureth sulfate. Hydrogenated didecenes have been quantified by GC-MS of extracts. A transparent shampoo containing 1.8% of hydrogenated didecenes delivered via a nanoemulsion was examined in the same way as the commercial shampoos. Finally, the substantivity data were compared with performance data from combability determination and hair volume measurements. Good correlations of analytical data and performance profiles have been obtained. PMID- 17728946 TI - Semi-permanent split end mending with a polyelectrolyte complex. AB - Split ends form through mechanical stresses during grooming procedures and are more likely to appear in hair damaged as a result of excessive combing forces. Although there are no conventional systems that will permanently mend split ends, a semi-permanent mending composition has been achieved through a polyelectrolyte complex. The complex is formed as a result of the ionic association of a cationic polymer, Polyquaternium-28, and an anionic polymer, PVM/MA Copolymer. Hair tresses containing tagged split ends are used in measuring mending efficacy. The tagging allows the fate of the split ends to be determined after different types of treatment regimens which test the durability of the mend. Monitoring of the repair and mending durability is carried out with the aid of a stereomicroscope. Results obtained with this method indicate that the complex both by itself and when formulated into a simple lotion provided a high level of split end mending not only after initial treatment but more importantly after combing showing the durability of the mend. Cumulative effects and durability to washing indicate that the polymer complex does not build up on the hair and rinses off with shampoo making possible its usage as a post shampoo treatment. The formulated lotion has higher durability performance as compared to a commercial product with a split end mending claim. The proposed mechanism of action entails a crosslinking microgel structure that infiltrates the damaged hair sites binding them together. This model is supported by the analysis of phase behavior, viscometry, Scanning Electron Microscopy, and absorption of ionic dyes. PMID- 17728947 TI - Hair breakage during combing. III. The effects of bleaching and conditioning on short and long segment breakage by wet and dry combing of tresses. AB - A recent publication (1), provided evidence for two types of hair breakage during combing, short segment breakage (approximately less than 1.27 cm) and longer segment breakage. We have confirmed these results and refined the separation distance between short and long segment breakage at about 2.54 cm. Furthermore, chemical bleaching increased both short and long segment breakage while a commercial hair conditioner decreased both types of breakage. Whether the hair is chemically bleached or conditioned, for dry combing, short segment breakage increases with increasing comb strokes, that is, short segment breakage increases as combing damages the ends of the hair, however, long segment breakage does not increase with increasing comb strokes. Wet combing provided a decrease in short segment breakage and an increase in long segment breaks, but no increase in breakage with increasing comb strokes. Mechanical combing of tresses shows similar results qualitatively, however the variance was too large and adjustments need to be made to provide for a larger number of broken hairs to bring the mechanical and hand combing results in line. For dry combing, as the comb descends through the hair, hairs above it are made parallel and those beneath are either made parallel or knot by, hairs looping around other hairs or hairs looping around comb teeth and other hairs several cm between the comb and the hair tips. As the comb advances through the looped/knotted hairs long breaks occur or as the comb descends near the tips wrapped ends can result. End wrapping by inertia & possibly static charge produces short segment breaks which are more severe if the hair is cut at 90 degrees versus a tapered cut. For wet combing, clumping of hairs by a capillary action produces fewer short segment breaks, by reducing end wrapping: however, crossed hair interactions occur & because of higher friction more severe snags arise higher up in the tress, and lower hair breaking load due to plasticization by water, producing a larger number of long segment breaks. The very best practical way to evaluate hair strength is by counting the actual number of short and long segment breaks and by considering both wet and dry combing. PMID- 17728949 TI - Abdominal cocoon associated with endometriosis. AB - Abdominal cocoon is a rare cause of intestinal obstruction in adults. Diagnosis is usually established at laparotomy in patients with recurrent attacks of non strangulating small bowel obstruction. A 40-year-old infertile Brazilian woman with intestinal obstruction and massive haemoserous ascites, due to coexistent ovarian endometriosis and abdominal cocoon, is reported. Abdominal pain, nausea, vomiting and a palpable mass, in addition to imaging of small bowel obstruction and thickened peritoneum, raised diagnostic suspicion. Higher awareness allows for early diagnoses and yields better results during management. PMID- 17728948 TI - Severe intra-abdominal haemorrhage: a consequence of two coinciding events. AB - Idiopathic thrombocytopenic purpura, an immune-mediated disease, usually has a relatively benign clinical course. Bleeding manifestations are mostly mucocutaneous and mild. Massive haemorrhages requiring transfusions or other interventions are rare, unless platelet counts are extremely low or other complicating conditions coexist. The rupture of an ovarian follicle is a very common benign condition in women of the reproductive age group. Any associated bleeding is unlikely to be significant, unless there is an underlying severe haemostatic derangement. We describe a 24-year-old Filipino woman presenting with severe abdominal pain and intra-abdominal haemorrhage requiring laparotomy, which revealed massive haemoperitoneum and a ruptured ovarian follicle. She had thrombocytopenia secondary to previously undiagnosed idiopathic thrombocytopenic purpura. This case illustrates how a combination of two otherwise common and benign clinical entities can result in a rare and potentially life-threatening event. PMID- 17728950 TI - Scrofuloderma from the acromioclavicular joint presenting as a chronic ulcer in an immunocompetent host. AB - A 53-year-old woman presented with a chronic, non-healing painless ulcer over her right clavicular area of a two-month duration. Skin biopsy, microbiological and radiological investigations confirmed the diagnosis of scrofuloderma arising from an underlying tuberculous infection of her acromioclavicular joint. She was treated successfully with anti-tuberculosis therapy with complete healing of the ulcer. Awareness of this uncommon presentation of osteoarticular tuberculosis may assist in earlier diagnosis. PMID- 17728951 TI - Pharyngomalacia as a cause of severe neonatal stridor. AB - A male neonate presented at 24 hours with stridor and respiratory distress. Flexible bronchoscopy showed pharyngomalacia, i.e. complete pharyngeal wall collapse during inspiration. Assessment of upper airway dynamics is emphasised. Pharyngomalacia seems to be a self-limiting condition in our case. PMID- 17728952 TI - Bacterial endocarditis treated with intramuscular teicoplanin. AB - Right-sided endocarditis caused by Staphylococcus aureus in parenteral drug abusers is potentially life-threatening, more so in the presence of pulmonary embolisation, and a course of parental antibiotics is required for at least four weeks. A combination of intravenous cloxacillin and aminoglycosides has proven efficacious for more than 90 percent of the patients. Intravenous vancomycin can also be used in cases of penicillin allergy or methicillin-resistant staphylococci. Intravenous teicoplanin, a glycopeptide with a similar antimicrobial profile to vancomycin, has been used with a somewhat lesser degree of success in these cases and is not recommended as first line therapy. We describe a 37-year-old man, a parenteral drug user, who had right-sided endocarditis, where in the absence of other alternatives, teicoplanin had to be administered intramuscularly and not intravenously. PMID- 17728953 TI - Sporadic paroxysmal non-kinesigenic dyskinesia: a frequently-misdiagnosed movement disorder. AB - Paroxysmal non-kinesigenic dyskinesia is a very rare movement disorder. Few cases have been reported in the literature so far. We present a 40-year-old man with non-kinesigenic paroxysmal dyskinesia, which was initially diagnosed as a psychogenic disorder. This case highlights the varied presentation of this condition and an excellent response to clonazepam. PMID- 17728954 TI - Non-familial cherubism. AB - Cherubism is a disease that usually affects the jaws in the paediatric population, mostly below five years of age. Radiologically, it closely resembles fibrous dysplasia and other giant cell lesions of the mandible. Computed tomography (CT) is helpful in defining the true extent of cherubic lesions, which is often not possible on radiographs due to the overlapping facial bones. We describe the radiographical and CT features of cherubism in a 12-year-old boy and highlight the ability of multidetector CT and various post-processing techniques to accurately depict the anatomical extent of the cherubic lesions. PMID- 17728955 TI - Congenital extrahepatic portosystemic venous shunt: imaging features. AB - Congenital extrahepatic portosystemic venous shunt (CEPS) is a rare anomaly. It causes metabolic derangements and is often associated with liver tumours and other anomalies. Imaging plays an important role in the diagnosis of CEPS. However, it may be misleading in determining the type of shunt. We present a six year-old girl with CEPS to illustrate the importance of histology in determining the presence of portal veins in the portal triad, which were too small to be seen on imaging. PMID- 17728956 TI - Digital mammography: opportunities and limitations. PMID- 17728957 TI - Albrecht von Graefe (1828-1870): founder of scientific ophthalmology. PMID- 17728958 TI - Ultrasonographical features of morbidly-adherent placentas. AB - Morbidly-adherent placentas manifest as placenta accreta, increta or percreta, depending on the depth of placental invasion. These conditions present high risks of severe obstetrical haemorrhage at delivery. The underlying pathology is due to defects in the decidua basalis caused by a variety of insults, such as previous surgery, excessive curettage or infection. The incidence of morbidly-adherent placentas is rising as the frequency of caesarean sections increase. Imaging plays an important role in the antenatal detection of this condition. Based on the case series seen at our local institution, we describe the imaging characteristics of this condition as seen on grayscale ultrasonography, colour/power Doppler ultrasonography, three-dimensional ultrasonography and magnetic resonance imaging. PMID- 17728959 TI - Moving into the digital era: a novel experience with the first full-field digital mammography system in Malaysia. AB - INTRODUCTION: Breast cancer is the commonest cancer in women and represents a significant problem from the clinical and public health perspectives. The aim of this paper is to report our experience of transitioning from screen-film mammography (SFM) to computed radiography mammography (CRM), and finally to full field digital mammography (FFDM), and to evaluate the performance of these three different types of mammographic systems. METHODS: A total of 2,734 mammograms using the three different systems were carried out at the University of Malaya Medical Centre. These examinations were evaluated based on time from start of examination to reporting, image quality, archiving, reject and repeat rates and overall diagnostic accuracy for SFM, CRM and FFDM. RESULTS: The time taken from the start of the examination to the radiologist interpretation and reporting were faster in both FFDM and CRM, compared to SFM. Image contrast with better contrast detail was almost equivocal for both CRM and FFDM, but lower for SFM. Easier image storage and archiving were available for CRM and FFDM in the form of magnetic optical discs, rather than hard copy storage as in SFM. The reject rate for FFDM was zero percent, compared to CRM and SFM which were two percent and two percent, respectively. The repeat rate for FFDM, CRM and SSFM was zero percent, 0.1 percent and 1.5 percent, respectively. Overall diagnostic accuracy of FFDM, CRM and SFM were comparable as no cancers were missed on all three systems as double blinded reporting was done. CONCLUSION: FFDM does improve quality of mammography service by providing better workflow time and archiving system, with good diagnostic accuracy. PMID- 17728960 TI - A review of 93 cases of severe preeclampsia in Singapore: are there risk factors for complications? AB - INTRODUCTION: This study aims to assess the epidemiology of severe preeclampsia in Singapore, the disease characteristics, maternal and perinatal outcome, and to identify risk factors for complications. METHODS: Data of 93 consecutive women with severe preeclampsia in KK Women's and Children's Hospital in Singapore was collected prospectively and analysed using the unpaired t-test for normally distributed continuous variables and Fisher's exact chi-square test for discrete variables. Multivariate logistic regression analysis was performed for prediction of complicated cases. RESULTS: The incidence of severe pre-eclampsia was 29.3 per 10,000 deliveries, with an increased risk in women who were aged more than 35 years and who were nulliparous. The risk was also increased in women of the Malay race and they also had the tendency to book later, compared with the other races. 43 percent of women had maternal complications, including eclampsia, haemolysis/elevated liver enzymes/low platelets syndrome, oliguria, pulmonary oedema and placental abruption. Significantly raised levels of uric acid (439.5 +/- 114.1 micromol/L versus 395.4 +/- 96.7 micromol/L, p-value equals 0.047) and aspartate transaminase (80.1 +/- 107.4 IU/L versus 38.8 +/- 16.1 IU/L, p-value equals 0.021) were found in those with complications, compared to those without complications. The average gestation at time of diagnosis was 33 weeks and the average gestation at delivery was 34 weeks. 89.3 percent of women required caesarean section and 59.1 percent of women were admitted to intensive care. CONCLUSION: Age, parity and race are risk factors for severe preeclampsia with increased levels of uric acid and aspartate transaminase found in the complicated cases. The morbidity and cost of treatment of severe preeclampsia are high with a large percentage requiring caesarean section and intensive care admission. PMID- 17728961 TI - Klebsiella pneumoniae respiratory isolates from 2000 to 2004 in a Malaysian hospital: characteristics and relation to hospital antibiotics consumption. AB - INTRODUCTION: Klebsiella pneumoniae ranks high as a cause of community-acquired pneumonia in hospitalised patients in Malaysia. METHODS: A retrospective study of 5,990 clinical respiratory specimens in patients, with a mean age of 54 (standard deviation 18.5) years, admitted to an urban-based general hospital between 2000 and 2004, was conducted. RESULTS: The percentages of K. pneumoniae isolates during these years were 11, 19.1, 41.4, 27.8 and 16.6 percent, respectively. During this time, the percentage of isolates resistant to ampicillin were consistently in excess of 80 percent, those resistant to cephalosporins were relatively stable between eight and 23 percent, while those resistant to beta lactam/beta-lactamase inhibitors [amoxicillin clavulanic acid/ ampicillin sulbactam] and aminoglycosides steadily increased between six and 58 percent. Compared with hospital consumption of these corresponding antibiotic classes, only beta-lactam/beta-lactamase inhibitors and aminoglycosides showed a clear trend of eight- and four-fold increases, respectively. Co-resistance rates in isolates resistant to ampicillin and amoxicillin-clavulanic acid/ampicillin sulbactam were generally low to second to third generation cephalosporins (less than 20 percent). CONCLUSION: Our local findings highlighted the changing trend in respiratory K. pneumoniae over a five-year period, and its escalating resistance to beta-lactam/beta-lactamase inhibitors and aminoglycosides that is possibly attributable to the widespread use of these antibiotics in our hospital. PMID- 17728962 TI - Bioequivalence evaluation of two different formulations of ciprofloxacin tablets in healthy volunteers. AB - INTRODUCTION: A bioequivalence study of two oral formulations of 500 mg tablets of ciprofloxacin (RAZA Pharmaniaga, Malaysia) as test and Ciprobay (Bayer AG, Germany) as reference, was carried out in 24 healthy human volunteers. Each volunteer received a single dose of ciprofloxacin. METHODS: The study method used was a double-blind, two-period, two-treatment, two-sequence, and crossover randomised design. Blood samples were taken before, and within 24 hours after drug administration. Plasma concentrations of ciprofloxacin were determined by a high-performance liquid chromatographic method with ultraviolet detection. The pharmacokinetic parameters, C(max) and T(max), were obtained directly from plasma data, k(e) was estimated by log-linear regression, and the area under the curve (AUC) was calculated by the linear trapezoidal rule. The parameters, AUC(0 infinity) and C(max), were tested for bioequivalence after log-transformation of data, while the differences of T(max) were evaluated nonparametrically. RESULTS: When AUC(0-infinity) and C(max) were analysed using analysis of variance, no statistically significant difference was observed between the two different formulations. The 90 percent confidence intervals of the mean values for the test/reference ratios were 0.95-1.07 for AUC(0-infinity) and 0.90-1.07 for C(max), respectively. Both of these values were within the bioequivalence acceptance range of 0.80-1.25. CONCLUSION: We found that both formulations are bioequivalent and, therefore, interchangeable. PMID- 17728963 TI - A national study of the epidemiology of pneumococcal disease among hospitalised patients in Singapore: 1995 to 2004. AB - INTRODUCTION: Infections with Streptococcus pneumoniae cause significant morbidity and mortality. In this study, we describe the epidemiology of pneumococcal disease based on hospitalisation rates for all age groups in Singapore. This is important for evaluating prevention and control strategies of pneumococcal disease. METHODS: We conducted a retrospective study of hospitalisation cases admitted to all public and private hospitals from 1995 to 2004. 4,275 hospitalisation records were extracted, based on the International Classification of Diseases, Ninth Revision (ICD-9) codes for pneumococcal disease. We analysed the demographics, type of pneumococcal disease, length of stay and case fatality of these cases. RESULTS: Our study showed that the mean annual hospitalisation rate for pneumococcal disease was 10.9 per 100,000 population from 1995 to 2004. The mean annual hospitalisation rate was highest in the young and the elderly. CONCLUSION: Baseline information on the epidemiology of pneumococcal disease is important for the formulation and evaluation of a national prevention and control programme. PMID- 17728964 TI - Tetrodotoxin poisoning: a clinical analysis, role of neostigmine and short-term outcome of 53 cases. AB - INTRODUCTION: Puffer fish (tetrodotoxin) poisoning is now a common form of poisoning throughout coastal countries, but its diagnosis and management are still unclear. In this paper, we aim to share our experience and to find out the toxic manifestations, lag period between ingestion of fish and development of symptoms, the short-term clinical outcome, and value of neostigmine in its management. METHODS: The study was carried out in the Department of Medicine and Paediatrics, Khulna Medical College Hospital, Khulna, Bangladesh, from May 1, 2001 to May 1, 2006. A total of 53 patients were admitted with the history of puffer fish ingestion. All the cases were clinically analysed from admission to discharge, for the following variables: Onset of symptoms in minutes after the ingestion of fish, toxic manifestations that developed after ingestion, relation of clinical outcome with approximate amount of fish ingested, and the role of neostigmine. RESULTS: All patients developed toxic manifestation. Important symptoms were perioral paraesthesia (38), weakness of all limbs (33), paraesthesia all over the body (34), headache (25), and difficulty in respiration. Eight patients died, probably due to respiratory muscle paralysis, of which five patients died immediately after admission. We used neostigmine in those patients who developed respiratory failure. 13 patients improved significantly (p-value is less than 0.5), while only three patients died. CONCLUSION: Because of the availability and affordability of puffer fish, the occurrence of tetrodotoxin poisoning throughout coastal countries is very likely. Therefore, health personnel should have enough knowledge regarding its toxic manifestations and management. PMID- 17728965 TI - Randomised, open label, controlled trial of celecoxib in the treatment of acute migraine. AB - INTRODUCTION: Migraine is a common disabling condition that results in considerable socioeconomic loss. The role of non-steroidal anti-inflammatory drugs (NSAIDs) in acute migraine has been well-established. We compared the efficacy of the cyclooxygenase-2 inhibitor celecoxib with the NSAID, naproxen sodium, in the treatment of acute migraine. METHODS: This was a randomised, open label, controlled trial. We selected patients with a diagnosis of migraine, based on the International Headache Society revised criteria. 60 patients were randomised to either celecoxib 400 mg (30 patients) or naproxen sodium 550 mg (30 patients). Patients took the study medicine for the first acute migraine episode that occurred during the study period and reported the headache reduction based on a visual analogue score (VAS). Patients were reviewed after a month to check on VAS at one and two hours, compared to the baseline. Any side effects of the medication were also recorded. RESULTS: Of the 52 patients who completed the study, eight did not experience any headaches. The mean VAS in the celecoxib group improved significantly from baseline (6.48 +/- 1.53) to one hour (4.28 +/- 2.11) and two hours (2.24 +/- 2.57) (p-value is less than 0.0005). The mean VAS in the naproxen sodium group also improved significantly from baseline (7.30 +/- 1.66) to one hour (4.81 +/- 2.50) and two hours (2.63 +/- 2.65) (p-value is less than 0.0005). However, there was no significant difference between the magnitudes of improvement between the treatment groups. The incidence of gastric pain was significantly higher in the naproxen sodium group (p-value is equal to 0.029). CONCLUSION: In comparison with naproxen sodium, celecoxib was equally effective in relieving pain in acute migraine and caused significantly less gastric pain. PMID- 17728966 TI - Association of glomerular and tubular dysfunction with glycaemic control, lipid, lipoprotein, apolipoprotein and antioxidant status in type 2 diabetes mellitus. AB - INTRODUCTION: This study was conducted to investigate the relationship of glomerular and tubular dysfunctions with glycaemic control, lipid, lipoprotein, apolipoproteins and antioxidant status in 72 patients with type 2 diabetes mellitus. METHODS: Urine albumin concentration was measured by immunoturbidimetric and urine N-acetyl-beta-D-glucosaminidase (NAG) and alanine aminopeptidase (AAP) activities with colorimetric methods. Glycated haemoglobin was measured using affinity chromatography. Erythrocyte glutathione reductase and glutathione peroxidase activities and serum levels of malondialdehyde, lipids, lipoproteins and apolipoproteins were determined in patients with type 2 diabetes mellitus. RESULTS: In univariate regression, urinary albumin excretion, and activities of NAG and AAP were associated with glycaemic control. These glycaemic factors included serum glucose concentrations and glycated haemoglobin. Urinary albumin excretion was also inversely correlated with erythrocyte glutathione peroxidase activity, and positively correlated with erythrocyte glutathione reductase activity. No significant associations were found with serum levels of insulin, lipids, lipoproteins, apolipoproteins, malondialdehyde or blood pressure. In multivariate regression, glycated haemoglobin was the most significant predictor of urinary albumin concentration and with erythrocyte glutathione reductase, whereas only glycated haemoglobin was the independent predictor of tubular dysfunctions. Erythrocyte glutathione peroxidase was not an independent predictor of urinary albumin excretion, after adjusting for glycated haemoglobin, glutathione reductase, systolic blood pressure, diastolic blood pressure and apolipoprotein B. CONCLUSION: In type 2 diabetes mellitus, both glomerular and tubular dysfunctions are dependent on glycaemic control. Glomerular, but not tubular, dysfunction is also significantly associated with increased glutathione reductase activity. PMID- 17728967 TI - Serum concentrations of cardiac troponin-I in patients with rheumatoid arthritis, systemic lupus erythematosus, primary Sjogren's syndrome and Graves' disease. AB - INTRODUCTION: Some reports in the literature suggest that cardiac troponin-I (cTnI) is falsely elevated in patients with seropositive rheumatoid arthritis (RA) because of the presence of rheumatoid factor (RF). But, there are no reports in the literature on cTnI concentrations in other autoimmune diseases. We therefore decided to measure the serum concentrations of cTnI in patients with seropositive and seronegative RA, systemic lupus erythematosus (SLE), primary Sjogren's syndrome (pSS) and Graves' disease (GD), in order to find out if this cardiac marker is falsely elevated or not. METHODS: Serum samples were drawn from 50 patients with seropositive RA, 50 patients with seronegative RA, 50 patients with SLE, 20 patients with pSS and 15 patients with GD. We measured cTnI levels using the Beckman Access Immunoassay System in these serum samples. RESULTS: Of the 50 patients with seropositive RA, five had cTnI levels higher than 0.1 ng per ml (the diagnostic value for myocardial infarction in our hospital laboratory), while none of the patients with seronegative RA, SLE, pSS, or GD had levels above this value. Furthermore, univariate regression analysis showed a positive association (r equals 0.35, p-value equals 0.02) between cTnI and RF in patients with seropositive RA. CONCLUSION: Using the Beckman Access Immunoassay System for cTnI quantification, it was found that some patients with seropositive RA had falsely-elevated cTnI, while none of the patients with seronegative RA, SLE, pSS, or GD had falsely-elevated cTnl. PMID- 17728968 TI - Airway foreign bodies in children: experience of 132 cases. AB - INTRODUCTION: Foreign body inhalation in children is not uncommon, and may escape notice by the parents as well as the physicians, because of the lack of knowledge of the exact history and inconclusive radiographical findings. METHODS: A retrospective analysis of airway foreign bodies in 132 children (80 males and 52 females) over a period of 20 years was conducted. Rigid bronchoscopy under general anaesthesia was done in 129 cases. RESULTS: The majority of patients (46 percent) were younger than three years of age. Duration of symptoms varied from less than six hours to three months. Definitive history of foreign body inhalation or sudden choking episodes were present in 71 children. The foreign body was successfully removed in 93.2 percent of the cases. Peanuts were the commonest foreign body. Foreign bodies were found in the right main bronchus in 62 cases, in the left main bronchus in 46 cases, and at vocal cord level in 7 cases. Chest radiographs were normal in 46 cases. CONCLUSION: Rigid bronchoscopy usually gives good results in detecting airway foreign bodies. It should be performed at the earliest opportunity even when the definitive history is not forthcoming and the chest radiograph is inconclusive. PMID- 17728969 TI - A rare case of ambiguous genitalia. AB - Genes on the Y chromosome are essential for normal sex determination and sex differentiation of male genitalia. However, genes on the X chromosome and other autosomes have been shown to be anti-testes and have a detrimental effect on this process. Addition of X chromosomes to the 46,XY karyotype results in seminiferous tubules dysgenesis, hypogonadism and malformed genitalia. We report a term male newborn with 49,XXXXY syndrome presenting with ambiguous genitalia, multiple extra-gonadal anomalies, facial dysmorphism, and radioulnar synostosis. PMID- 17728970 TI - Intestinal atresia of co-twin after spontaneous cessation of blood flow through an acardiac twin. AB - A 33-year-old woman was diagnosed at 15 weeks gestation with a twin pregnancy complicated by an acardiac acephalic foetus. The patient opted for expectant management with close foetal surveillance. Serial ultrasonography showed polyhydramnios at 22 weeks gestation. However, subsequent scans over the next two weeks showed cessation of blood flow in the acardiac foetus, decreasing size of the foetal mass, as well as gradual resolution of the polyhydramnios. Subsequent follow-up was rather uneventful and she underwent an uncomplicated elective caesarean section at 35 weeks, resulting in a healthy 2,820 g girl. The baby was found to have intestinal atresia at birth. She underwent surgery successfully and was well when discharged. The possible causes and pathophysiology of intestinal atresia are discussed. PMID- 17728971 TI - Twin lithopaedions: a rare entity. AB - Lithopaedion (stone baby) is the name given to an extrauterine pregnancy that evolves to foetal death and calcification. There are around 300 cases reported in the world medical literature to date. We report the case of a 40-year-old woman who presented with features of acute intestinal obstruction (abdominal distention, vomiting and absolute constipation) for a week. She had a past history of a missed abortion in the fifth month of gestation, eight years prior to this presentation, one which we thought to be irrelevant to the present illness. However, complementary investigations, including scout abdominal radiographs and ultrasonography of the abdomen and pelvis, were done before the operation. The abdominal radiograph showed two opaque globular masses on either side of the lower abdomen with distended small intestinal loops. Exploratory laparotomy was performed and a portion of strangulated small bowel attached to a solid globular mass behind the left ovary was removed, with a subsequent resection of the gut and end-to-end anastomosis. Upon removal of a thick membrane from the globular mass, a dead five-month-old calcified foetus was recovered. In the right iliac fossa, a similar mass was removed and another dead calcified foetus of similar age was recovered. PMID- 17728972 TI - Clinics in diagnostic imaging (118). AB - An 18-month-old boy presented with delayed milestones, hypotonia, strabismus and an episode of seizure. Magnetic resonance (MR) imaging of the brain revealed abnormally-oriented and thickened superior cerebellar peduncle, giving rise to the characteristic molar tooth sign on axial images. The isthmus was thinned out, with widened interpeduncular cistern and hypoplastic vermis. The clinical and MR imaging features were diagnostic of Joubert syndrome. PMID- 17728975 TI - The effectiveness of humane teaching methods in veterinary education. AB - Animal use resulting in harm or death has historically played an integral role in veterinary education, in disciplines such as surgery, physiology, biochemistry, anatomy, pharmacology, and parasitology. However, many non-harmful alternatives now exist, including computer simulations, high quality videos, ''ethically sourced cadavers'' such as from animals euthanased for medical reasons, preserved specimens, models and surgical simulators, non-invasive self-experimentation, and supervised clinical experiences. Veterinary students seeking to use such methods often face strong opposition from faculty members, who usually cite concerns about their teaching efficacy. Consequently, studies of veterinary students were reviewed comparing learning outcomes generated by non-harmful teaching methods with those achieved by harmful animal use. Of eleven published from 1989 to 2006, nine assessed surgical training--historically the discipline involving greatest harmful animal use. 45.5% (5/11) demonstrated superior learning outcomes using more humane alternatives. Another 45.5% (5/11) demonstrated equivalent learning outcomes, and 9.1% (1/11) demonstrated inferior learning outcomes. Twenty one studies of non-veterinary students in related academic disciplines were also published from 1968 to 2004. 38.1% (8/21) demonstrated superior, 52.4% (11/21) demonstrated equivalent, and 9.5% (2/21) demonstrated inferior learning outcomes using humane alternatives. Twenty nine papers in which comparison with harmful animal use did not occur illustrated additional benefits of humane teaching methods in veterinary education, including: time and cost savings, enhanced potential for customisation and repeatability of the learning exercise, increased student confidence and satisfaction, increased compliance with animal use legislation, elimination of objections to the use of purpose-killed animals, and integration of clinical perspectives and ethics early in the curriculum. The evidence demonstrates that veterinary educators can best serve their students and animals, while minimising financial and time burdens, by introducing well designed teaching methods not reliant on harmful animal use. PMID- 17728974 TI - Safety testing of cell-based medicinal products: opportunities for the monocyte activation test for pyrogens. AB - The European Partnership for Alternative Approaches to Animal Testing (EPAA) pointed out the need to involve authorities throughout the process of validation and legal acceptance of alternatives to animal experiments. The Paul-Ehrlich Institute (PEI), Federal Agency for Sera and Vaccines, is the national competent authority in Germany which is responsible for the quality and safety of biologicals including blood and cell-based products. This paper is intended to contribute to the discussion concerning the use of alternative methods in safety testing of medicinal products and considers the scientific work of the PEI in this field. From a regulator's perspective, adequate demonstration of safety and quality of medicinal products are of major interest. Additionally, the availability of the products to the patient has to be taken into consideration. It has to be carefully explored whether the respective in vitro method for demonstration of non-clinical safety as part of the non-clinical development programme is able to guarantee safety level comparable to the corresponding experiment in animals. The topics cited above shall be discussed in this paper using the example of the Alternative Pyrogen Test or also called Monocyte Activation Test. The Alternative Pyrogen Test could serve as paradigm to exemplify how an alternative test can provide at least a comparable level of safety estimation in comparison with a conventional animal test. Furthermore, this alternative test creates additional information which cannot be obtained from the animal experiment, and might also open further scientific insight into the mechanisms of pyrogenicity and acute pro-inflammatory reactions in patients. This test method allows the definition of pyrogen limits for medicinal products. Due to its use of relevant cell systems this in vitro test might contribute significantly to safety assessments of advanced medicinal products during the pre clinical phase. PMID- 17728976 TI - Serum-free culturing of mammalian cells--adaptation to and cryopreservation in fully defined media. AB - Long term storage of living cells is a central issue in cell biology and medicine. In addition to the cryoprotectant dimethyl sulphoxide (DMSO), foetal bovine serum (FBS) is often added to the freezing medium for the cryoconservation of serum dependent cell lines. FBS, with its high protein content, protects cells against shear forces and gives the medium a desirable osmotic environment with a physiological viscosity. However, the harvesting of FBS is painful for the foetus and should be avoided for ethical reasons. In this work we describe the adaptation of several commonly used cell lines to serum- and protein-free media; however, such cell lines should not be frozen in a conservation medium containing serum. We tested the synthetic surfactant ''Pluronic F68'', known to protect mammalian cells grown in serum-free bioreactors (Papoutsakis, 1991), as an active cryoprotectant. In samples containing 0.1 to 1% Pluronic F68, we found a significant increase in viable cells after thawing. Values up to 115% of starting cell number indicate that the cells proliferate within the first 24 hours after thawing, a property which was not observed in cryoconservation media without Pluronic F68. PMID- 17728977 TI - Alternatives in pharmaceutical toxicology: global and focussed approaches--two case studies. AB - Safety testing of potential drugs has been and will continue to be a challenging task for the toxicologist in the pharmaceutical industry. We present two examples for the use of target-specific cell models to detect and assess species-specific toxicity. In the first example, adrenal models based on primary cells as well as a permanent human adrenal cell line were used. Both cell systems enabled a good prediction of adrenal effects in rodents, non-rodents and humans. The second example made use of primary hepatocytes. In this project, a potential drug candidate showed unexpected toxicity in vitro as well as species-specific cytochrome P450 (CYP) induction in vivo. We therefore analysed CYP induction and gene expression signatures in rat and human hepatocytes as well as in samples from in vivo animal toxicity studies. By this approach, the rat hepatocyte model correctly predicted the effects observed in rats and the in vitro/in vivo comparison enabled a solid extrapolation of consequences in humans. These examples demonstrate that an intelligent testing strategy, using alternative methods, can enable a meaningful safety assessment for humans by adding a ''tailor-made'' range of technologies to ''classic'' toxicological methods. PMID- 17728978 TI - Modeling DNA beacons at the mesoscopic scale. AB - We report model calculations on DNA single strands which describe the equilibrium dynamics and kinetics of hairpin formation and melting. Modeling is at the level of single bases. Strand rigidity is described in terms of simple polymer models; alternative calculations performed using the freely rotating chain and the discrete Kratky-Porod models are reported. Stem formation is modeled according to the Peyrard-Bishop-Dauxois Hamiltonian. The kinetics of opening and closing is described in terms of a diffusion-controlled motion in an effective free-energy landscape. Melting profiles, dependence of melting temperature on loop length, and kinetic time scales are in semiquantitative agreement with experimental data obtained from fluorescent DNA beacons forming poly(T) loops. Variation in strand rigidity is not sufficient to account for the large activation enthalpy of closing and the strong loop length dependence observed in hairpins forming poly(A) loops. Implications for modeling single strands of DNA or RNA are discussed. PMID- 17728979 TI - Strength and failure of cemented granular matter. AB - Cemented granular materials (CGMs) consist of densely packed solid particles and a pore-filling solid matrix sticking to the particles. We use a sub-particle lattice discretization method to investigate the particle-scale origins of strength and failure properties of CGMs. We show that jamming of the particles leads to highly inhomogeneous stress fields. The stress probability density functions are increasingly wider for a decreasing matrix volume fraction, the stresses being more and more concentrated in the interparticle contact zones with an exponential distribution as in cohesionless granular media. Under uniaxial loading, pronounced asymmetry can occur between tension and compression both in strength and in the initial stiffness as a result of the presence of bare contacts (with no matrix interposed) between the particles. Damage growth is analyzed by considering the evolution of stiffness degradation and the number of broken bonds in the particle phase. A brutal degradation appears in tension as a consequence of brittle fracture in contrast to the more progressive nature of damage growth in compression. We also carry out a detailed parametric study in order to assess the combined influence of the matrix volume fraction and particle matrix adherence. Three regimes of crack propagation can be distinguished corresponding to no particle damage, particle abrasion and particle fragmentation, respectively. We find that particle damage scales well with the relative toughness of the particle-matrix interface with respect to the particle toughness. This relative toughness is a function of both matrix volume fraction and particle-matrix adherence and it appears therefore to be the unique control parameter governing transition from soft to hard behavior. PMID- 17728980 TI - Stretching dynamics of semiflexible polymers. AB - We analyze the nonequilibrium dynamics of single inextensible semiflexible biopolymers as stretching forces are applied at the ends. Based on different (contradicting) heuristic arguments, various scaling laws have been proposed for the propagation speed of the backbone tension which is induced in response to stretching. Here, we employ a newly developed unified theory to systematically substantiate, restrict, and extend these approaches. Introducing the practically relevant scenario of a chain equilibrated under some prestretching force f (pre) that is suddenly exposed to a different external force f (ext) at the ends, we give a concise physical explanation of the underlying relaxation processes by means of an intuitive blob picture. We discuss the corresponding intermediate asymptotics, derive results for experimentally relevant observables, and support our conclusions by numerical solutions of the coarse-grained equations of motion for the tension. PMID- 17728981 TI - Solution of the Poisson-Nernst-Planck equations in the cell-substrate interface. AB - Electrogenic cells are able to generate electrical signals which can be measured by various invasive electrophysiological methods such as patch-clamp or sharp microelectrode recordings. Growing cells on the surfaces of e.g. metal microelectrodes or field-effect transistors allows the recording of an extracellular component of these signals. For an understanding of such extracellular signals it is mandatory to get detailed topographical as well as electrical information about the cell-sensor interface. In a first approximation, this interface can be described by a flat disk between cell membrane and sensor surface. For a correct description of the signals, the electrodiffusion of ions in this interface is modeled by using the stationary Poisson-Nernst-Planck equations. We solve the equations analytically, and derive expressions for the potential, the ionic charge densities, and the seal resistance. The results provide a method for determining the distance h between sensor surface and cell membrane. For human embryonic kidney cells, we receive h approximately 70 nm. Comparison with literature shows good agreement. PMID- 17728982 TI - Cytosolic phospholipase A2 regulation in the hibernating thirteen-lined ground squirrel. AB - Cytosolic calcium-dependent phospholipase A(2) (cPLA(2)) has multiple roles including production of arachidonic acid (a key player in cellular signaling pathways) and membrane remodeling. Additionally, since catabolism of arachidonic acid generates free radicals, the enzyme is also implicated in ischemic injury to mammalian organs. Regulation of cPLA(2) could be important in the suppression and prioritization of cellular pathways in animals that undergo reversible transitions into hypometabolic states. The present study examines the responses and regulation of cPLA(2) in skeletal muscle and liver of hibernating thirteen lined ground squirrels, Spermophilus tridecemlineatus. cPLA(2) activity decreased significantly by 43% in liver during hibernation, compared with euthermic controls, and K(m) values for arachidonoyl thio-PC substrate fell in both organs during hibernation to 61% in liver and 28% in muscle of the corresponding euthermic value. To determine whether these responses were due to a change in the phosphorylation state of the enzyme, Western blotting was employed using antibodies recognizing phospho-Ser(505) on alpha-cPLA(2). The amount of phosphorylated alpha-cPLA(2) in hibernator liver was just 38% of the value in euthermic liver. Furthermore, incubation of liver extracts under conditions that enhanced protein phosphatase action caused a greater reduction in the detectable amount of phospho-Ser(505) enzyme content in euthermic, versus hibernator, extracts. The data are consistent with a suppression of cPLA(2) function during torpor via enzyme dephosphorylation, an action that may contribute to the well developed ischemia tolerance and lack of oxidative damage found in hibernating species over cycles of torpor and arousal. PMID- 17728983 TI - Arthroscopic repair of rotator cuff tears. AB - OBJECTIVE: Regain of shoulder function and freedom of pain through arthroscopic fixation of the torn rotator cuff using anchors and tension bands. INDICATIONS: Isolated full-substance rupture of the supraspinatus. Full-substance tear of the supraspinatus and the superior part of the infraspinatus. Incomplete tears affecting the superior part of the subscapularis, either isolated or associated with rupture of the supraspinatus. For lesions of the long head of the biceps: tenodesis in patients < 60 years of age or in blue-collar workers; tenotomy in all other instances. CONTRAINDICATIONS: Fatty infiltration of infraspinatus and subscapularis of stage 3 and 4. Frozen shoulder in the active phase. Narrowing of the subacromial space (< 7 mm). Complete tear of the subscapularis. Complete tear of the posterosuperior cuff reaching the teres minor. Patients >or=65 years. SURGICAL TECHNIQUE: Subacromial bursoscopy and glenohumeral arthroscopy. Repair of supraspinatus using a posterior portal and an inside-out anterior portal, associated with one or two additional anterolateral portals. Attachment with a single row of anchors. Tenotomy/tenodesis of long head of biceps, if indicated. RESULTS: 50 patients, follow-up of an average of 24 months. 34 watertight repairs, Constant Score 85.2; complete tear or leakage in 16 patients, Constant Score 77.4 points. PMID- 17728984 TI - The Targon PH nail as an internal fixator for unstable fractures of the proximal humerus. AB - OBJECTIVE: Exercise-stable internal fixation of unstable fractures of the proximal humerus. INDICATIONS: Unstable humeral head fractures with two to four fragments. Unstable fractures of the proximal humerus. Pseudarthroses of the proximal humerus. CONTRAINDICATIONS: Stable proximal humerus fractures (impacted, dynamic stability confirmed by image intensifier). Dislocated fractures with rupture of the nutrient arteries to the region of the humeral head. Fractures with headsplit. Relative: incomplete or nonexistent bone stock around the nail insertion site in the region of the humeral head. SURGICAL TECHNIQUE: Exposure of the nail insertion site at the apex of the humeral head by division of the deltoid muscle and short incision of the supraspinatus tendon posterior to the biceps tendon. Open or closed reduction and extraction of a cylindrical bone segment ready for nail insertion through the humeral head. The nail is advanced into the humeral shaft and locked in the humeral head with four proximal interlocking screws and into the diaphysis with two fixation screws inserted with the help of the targeting device. Exact monitoring of implant position using the image intensifier to ensure that the implant is not protruding. Closure of the rotator cuff and transosseous refixation of the deltoid muscle to the acromion. POSTOPERATIVE MANAGEMENT: Gilchrist bandage for a few days or for 4 weeks in noncompliant patients preventing to lean on the operated arm. External rotation is restricted to 15 degrees for 6 weeks. All other movements are permitted up to the pain threshold. Physiotherapeutic treatment to prevent adhesions in the subacromial space. RESULTS: From December 2000 to spring 2004, 133 patients (average age: 74.9 years) with 137 unstable proximal humeral fractures were treated surgically. 97 patients with 99 operated shoulders were followed up for at least 7 months. The patients' average age at follow-up was 74.9 +/- 13.6 years (20-102 years). A Constant Score of 60.0 +/- 16.8 points was achieved and 84.8 +/ 19.4% and 84.0 +/- 15.5% on the age- and gender-related as well as side-related Constant Scores. PMID- 17728985 TI - Percutaneous osteosynthesis of humeral head fractures. AB - OBJECTIVE: Reduction and fixation of displaced fractures of the humeral head by percutaneous methods. Early functional postoperative management. INDICATIONS: Simple subcapital fractures of the humerus, AO 11A2, A3. Multifragmentary fractures of the proximal humerus, AO 11B1, B2, C1, (C2). CONTRAINDICATIONS: Head split fractures. Fracture dislocations. Severe osteoporosis. SURGICAL TECHNIQUE: The head fragment, generally impacted in valgus, is lifted by means of an elevator inserted percutaneously. The head is brought into the correct position and fixed to the shaft with two crossed Kirschner wires. The Kirschner wires are clamped into a locking device attached to the lateral cortex of the humerus by one screw to prevent slippage. Displaced tubercles are also reduced percutaneously by the aid of small bone hooks and are stabilized by insertion of cannulated screws. POSTOPERATIVE MANAGEMENT: Shoulder bandage for 3 weeks. Depending on the stability achieved during operation gentle exercising can be commenced from the 1st postoperative day with the arm bandaged. RESULTS: 200 patients (78 men, 122 women) were followed up at least 2 years (24-81 months) postoperatively. The average age was 61.6 years (14-103 years). The average Constant Score for four-part fractures was 87%. 24% of the patients had to be operated on a second time (shortening of the wires or reosteosyntheses). In 8.5% secondary change of management was necessary. In 3% clinically relevant avascular head necrosis occurred, and pseudarthrosis in 3%. PMID- 17728986 TI - [Fixation of syndesmotic disruption using bioresorbable screws]. AB - OBJECTIVE: Fixation of syndesmotic disruption using bioresorbable screws to avoid secondary surgery for removal of the positioning screw. INDICATIONS: Syndesmotic ligament disruption, i.e., associated with ankle fractures (AO type B and C injuries). CONTRAINDICATIONS: Allergies to bioresorbable materials such as sutures containing polylactic acids. Open fractures with severe comminution or bone loss. Successful conservative management in older patients. Nonambulatory patients. SURGICAL TECHNIQUE: In case of a syndesmotic disruption, one or two cannulated bioresorbable positioning screws are placed bicortically under image intensifier control to allow healing of the distal ligamentous junction between the fibula and tibia. Screws must be placed proximal to the cartilaginous part of the tibiofibular joint to avoid uneventful cartilage damage and arthrosis. POSTOPERATIVE MANAGEMENT: Postoperatively, most patients are treated with a non weight-bearing cast for 6 weeks. Casts are changed after 1 and 2 weeks postoperatively. After 6 weeks, weight bearing is initiated. Return to physically demanding work and sports is allowed after 10-12 weeks. RESULTS: Eight patients with a 6- to 12-month follow-up period showed good clinical and radiologic results. PMID- 17728987 TI - One-third tubular hook plate. AB - It is often the case that screws cannot be firmly anchored in small, marginal joint fragments. This is especially relevant in osteoporotic bone. By redesigning the last plate hole of a one-third tubular plate to function as a hook, these bone fragments can be securely grasped and stabilized. Placing two plates on top of one another further improves mechanical strength. PMID- 17728988 TI - Total hip arthroplasty by a minimally invasive, direct anterior approach. AB - OBJECTIVE: Implantation of a total hip replacement device through a direct anterior approach to the hip joint with minimal trauma to adjacent tissue. INDICATIONS: All conventional total hip replacements, irrespective of age and bone quality. CONTRAINDICATIONS: Destruction of the proximal femur (tumor, fracture). Severe dysplasia and hip dislocation. Morbid obesity (body mass index [BMI] > 30 kg/m(2)) can be a relative contraindication during the learning curve. SURGICAL TECHNIQUE: Supine position of the patient on the operating table with the possibility of hyperextension in the mid-table in order to facilitate femoral exposure. Anterior incision, 6-9 cm long, starting approximately 2 cm lateral and 5 cm distal of the anterior iliac spine. Incision of the fascia, blunt preparation in the intermuscular space between tensor fasciae latae muscle and sartorius muscle. Excision of the anterior parts of the capsule. Osteotomy of the femoral neck, removal of the head. Reaming of the acetabulum and implantation of the acetabular component. Exposure of the femur by hyperextension, adduction and external rotation of the leg, incision of the posterior capsule for easy anteriorization of the femur. Reaming and implantation of the femoral component. RESULTS: 116 consecutive hips in 111 patients were operated on between August 2004 and December 2005. 17 patients were excluded due to fracture or severe dysplasia (Crowe 3 and 4). Mean age was 62.5 years (range, 46-84 years), mean BMI amounted to 23.1 kg/m(2) (range, 18.1-37.7 kg/m(2)). The implantation of a total hip replacement device could be accomplished safely in all patients. No severe intraoperative complication requiring a change of the planned procedure or any additional surgical measures was noted. Mean surgical time was 79 min (45-150 min). The operative time was decreasing gradually during the study period. The mean preoperative Japanese Orthopaedic Association (JOA) score of 47.2 points (range, 18-63 points) improved to 92.3 points (range, 67-100 points) at 3 months postoperatively (p < 0.001) and 94.2 (range, 72-100 months) at the latest follow up at an average of 17 months (range, 9-26 months). PMID- 17728989 TI - Wastewater toxicity of tannin- versus chromium-based leather tanneries in Marrakesh, Morocco. AB - The toxicity of leather tanning wastewater from a traditional tannery (TT), which is based on vegetable tannin (VT), was compared with wastewater from a tannery combining the use of chromium-based tanning (CT) with VT-based tanning operations. Wastewater samples from a TT and a CT plant as well as from five sewer sampling points were collected in Marrakesh, Morocco, and the concentrations of VT and some selected inorganics were measured. A set of bioassays were used to test wastewater toxicity in sea urchin (Paracentrotus lividus) embryos and sperm, in Daphnia magna, and in marine microalgae (Dunaliella tertiolecta). Toxicity end points included: (1) developmental defects, embryonic mortality, sperm fertilization success, and offspring damage in sea urchins; (2) D. magna immobilization; and (3) algal growth rate inhibition. Toxicity tests on TT and CT effluents (TTE and CTE) were run at dilutions ranging from 0.1% to 2% (sea urchins and algae) or up to 12% in D. magna. Parallel bioassays were run on VT extract (VTE) at nominal tannin concentrations ranging from 0.1 to 10 mg l(-1). The results showed higher toxicity of CTE compared with TTE. CTE toxicity in sea urchins and algae showed concentration-related trends, whereas TTE exerted hormetic effects at levels of 0.1% to 0.2% and toxic effects at levels >or=1%. The same trends were observed for VTE, suggesting a prevailing role of tannin in TTE-associated effects. The moderate wastewater toxicity of VT-based tanneries might prompt interest in the VT tanning process. PMID- 17728990 TI - Postimpoundment time course of increased mercury concentrations in fish in hydroelectric reservoirs of northern Manitoba, Canada. AB - Mercury (Hg) concentrations in fish in boreal reservoirs have been shown to be increased for up to 3 decades after impoundment. However, the time course of increased concentrations is not well known. The purpose of this study was to determine the evolution of Hg concentrations in fish in the boreal reservoirs of northern Manitoba, Canada, and its relationship with severity of flooding. We determined total Hg concentrations in three species of fish for up to 35 years after impoundment in 14 lakes and lake basins. Postimpoundment trends depended on fish species and reservoir. In the benthivorous lake whitefish (Coregonus clupeaformis), Hg concentrations increased after flooding to between 0.2 and 0.4 microg g(-1) wet weight compared with preimpoundment concentrations between 0.06 and 0.14 microg g(-1) and concentrations in natural lakes between 0.03 and 0.06 microg g(-1). Hg concentrations in lake whitefish were usually highest within 6 years after lake impoundment and took 10 to 20 years after impoundment to decrease to background concentrations in most reservoirs. Hg concentrations in predatory northern pike (Esox lucius) and walleye (Sander vitreus) were highest 2 to 8 years after flooding at 0.7 to 2.6 microg g(-1) compared with preimpoundment concentrations of 0.19 to 0.47 microg g(-1) and concentrations in natural lakes of 0.35 to 0.47 microg g(-1). Hg concentrations in these predatory species decreased consistently in subsequent years and required 10 to 23 years to return to background levels. Thus, results demonstrate the effect of trophic level on Hg concentrations (biomagnification). Peak Hg concentrations depended on the amount of flooding (relative increase in lake surface area). Asymptotic concentrations of approximately 0.25 microg g(-1) for lake whitefish and 1.6 microg g(-1) for both walleye and northern pike were reached at approximately 100% flooding. Downstream effects were apparent because many reservoirs downstream of other impoundments had higher Hg concentrations in fish than would be expected on the basis of flooding amount. PMID- 17728991 TI - Chub (Leuciscus cephalus) as a bioindicator of contamination of the Vltava River by synthetic musk fragrances. AB - Synthetic musk fragrances, which are contained in almost all scented consumer products, enter aquatic environment mainly by way of wastewater paths. To monitor contamination of the Vltava River by these relatively persistent chemicals in the surroundings of Prague industrialized agglomeration, chub (Leuciscus cephalus) was employed as a bioindicator. Validated gas chromatography-mass spectrometry method was used for fish sample examination. Polycyclic musks, represented by 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta-(gamma)-2-benzopyran (galaxolide) and 1-(5,6,7,8-tetrahydro-3,5,5,6,8,8-hexamethyl-2-naphthalenyl) ethanone (tonalide) were the most abundant representatives of this group; their levels in fillets were in the range of 1.7 to 105.9 microg/kg and 0.9 to 19.3 microg/kg wet weight, respectively. Nitro-musks, musk ketone, and musk xylene were also detected in most samples; nevertheless, their levels were lower, 85% of the time, with median concentrations of 18 to 234 ng/L and maximum concentrations of 198 to 4141 ng/L. Individually, concentrations of nutrients and organic chemicals were much lower than those shown previously in laboratory and field experiments to have reproductive effects on amphibians. Nevertheless, hellbenders are exposed to a variety of chemicals with potential estrogenic effects. Our study establishes the basis to examine the specific effects of the detected concentrations, alone and in combination, on the Ozark hellbenders. PMID- 17728993 TI - Flow cytometry and cell sorting. AB - Flow cytometry and cell sorting are well-established technologies in clinical diagnostics and biomedical research. Heterogeneous mixtures of cells are placed in suspension and passed single file across one or more laser interrogation points. Light signals emitted from the particles are collected and correlated to entities such as cell morphology, surface and intracellular protein expression, gene expression, and cellular physiology. Based on user-defined parameters, individual cells can then be diverted from the fluid stream and collected into viable, homogeneous fractions at exceptionally high speeds and a purity that approaches 100%. As such, the cell sorter becomes the launching point for numerous downstream studies. Flow cytometry is a cornerstone in clinical diagnostics, and cheaper, more versatile machines are finding their way into widespread and varied uses. In addition, advances in computing and optics have led to a new generation of flow cytometers capable of processing cells at orders of magnitudes faster than their predecessors, and with staggering degrees of complexity, making the cytometer a powerful discovery tool in biotechnology. This chapter will begin with a discussion of basic principles of flow cytometry and cell sorting, including a technical description of factors that contribute to the performance of these instruments. The remaining sections will then be divided into clinical- and research-based applications of flow cytometry and cell sorting, highlighting salient studies that illustrate the versatility of this indispensable technology. PMID- 17728994 TI - Gamma-knife radiosurgery in the treatment of trigeminal schwannomas. AB - BACKGROUND: Trigeminal nerve schwannomas account for 0.07%-0.28% of all intracranial tumours. Advances in skull base surgery have led to more aggressive resection of these tumours, but surgery may associated with development of new neurological deficits. METHODS: In this report, we analyse the long-term results 15 patients with newly diagnosed or residual/recurrent trigeminal schwannoma who underwent gamma-knife treatment. FINDINGS: During a mean 61 months of follow-up, MRI revealed reduction of tumour size in 13 and no size change in 2 patients. The tumour growth control rate was 100% and only 1 patient had transient facial numbness and diplopia. CONCLUSIONS: For patients with small to moderate size trigeminal schwannomas, gamma-knife radiosurgery is associated with good tumour control and a minimal risk of adverse radiation effects. PMID- 17728995 TI - Quality of life in adult patients with primary intracranial arachnoid cysts. AB - BACKGROUND: Primary arachnoid cysts are benign developmental lesions of arachnoid mater. Arachnoid cysts may be detected due to various neurological symptoms, or they may be encountered as incidental findings of neuroimaging. Consequently, a significant share of the patients seems asymptomatic. There are diverging opinions about the clinical importance of cyst sizes, cyst location and degree of volume reduction after surgery, hence contributing to controversies regarding indications for surgical treatment. We present the first study assessing internationally established parameters of quality of life and mental health in a clinical-outcome analysis of adult patients with arachnoid cysts. METHOD: Ninety two adult patients with arachnoid cysts who had been referred to our department over the last 16 years were included. Forty-seven patients had undergone surgery and 45 patients had not been operated on. Data for analysis was based on both medical records and questionnaires sent out by mail. Quality of life was assessed by the Short Form 36 Health Survey (SF-36), and mental health was further evaluated by the Hospital Anxiety and Depression Scale (HADS). Seventy-one percent of patients responded to our questionnaires. FINDINGS: There was a great variation in the presenting symptoms, seemingly without any relation to cyst localisation. Patients with arachnoid cysts seem to have a reduced quality of life and a very high prevalence of anxiety compared to a healthy normal population. Men presented lower outcome scores than women. Subjects with symptoms, that we retrospectively labeled biologically comprehensible, tended to have higher quality of life, less anxiety and better subjective symptom relief after surgery. CONCLUSION: Our arachnoid cyst population had a low employment status, decreased quality of life scores and prevalent symptoms of anxiety. We argue that the arachnoid cysts are, in most cases, not directly related to these studied parameters. We speculate that our findings may reflect the demographic characteristics of adults likely of being diagnosed with incidental cysts. A better clinical outcome for patients with biologically plausible symptoms supports a neurobiological approach in the selection of patients suited for surgery. PMID- 17728996 TI - Maximal electroshock induces changes in some markers of oxidative stress in mice. AB - The oxidative/antioxidative status was investigated in maximal electroshock induced seizures in mice, a well established model of generalized seizures in humans. Mice were given a single electroshock resulting in tonic convulsions. Total antioxidant capacity (TAC), lipid peroxidation intensity and glutathione peroxidase (GSH-Px) activity was measured spectrophotometrically in the brain, plasma and erythrocytes collected from mice sacrificed at different time points after stimulation. For comparison, sham-stimulated and subeffectively stimulated (no tonic seizures) mice were used. Tonic seizures caused an immediate increase in GSH-Px activity in the brain and during the following three hours the enzyme activity decreased below control values. Similar changes were seen after subconvulsive stimulations, however, a significant increase occurred only one hour after electroshock. A marked TAC reduction in the brain was observed three hours after subconvulsive stimulations. Nevertheless, no significant changes in TAC after tonic seizures were noted. TAC in plasma was significantly reduced three hours after both subconvulsive and convulsive stimulation. Marked reduction of lipid peroxidation intensity in the brain and plasma was recorded after both modes of stimulation. In conclusion, pronounced changes in oxidative/antioxidative status in mice following electroshock are caused by both convulsive and subconvulsive stimuli. Participation of oxidative stress in seizures and pathophysiology of epilepsy awaits further clarification. PMID- 17728997 TI - A novel class of amino-alkylcyclohexanes as uncompetitive, fast, voltage dependent, N-methyl-D-aspartate (NMDA) receptor antagonists--in vitro characterization. AB - The fact that potent NMDA receptor channel blockers produce phencyclidine-like psychotropic symptoms in man and rodents implies that uncompetitive antagonism of NMDA receptors may not be a promising therapeutic approach. However, recent data indicate that agents with moderate affinity such as memantine and neramexane (MRZ 2/579) are useful therapeutics due to their strong voltage-dependency and rapid unblocking kinetics. Merz has developed a series of novel uncompetitive NMDA receptor antagonists based on an amino-alkylcyclohexane structure. These compounds displaced [(3)H]-MK-801 binding to rat cortical membranes with K(i) values between 1 and 100 microM and inward current responses of cultured hippocampal neurons to NMDA were antagonized in a strongly voltage-dependent manner with rapid blocking/unblocking kinetics. Three of these compounds, with similar biophysical properties to memantine, were chosen for development. MRZ 2/759 (1-ethenyl-3,3,5,5-tetramethyl-cyclohexylamine), 2/1010 (1,3,3,5 tetramethyl-6-azabicyclo[3.2.1]octane) and 2/1013 (8,8,10,10-tetramethyl-1 azaspiro[5.5] undecane) displaced [(3)H]-MK-801 binding with K(i) values of 1.18, 2.59 and 3.64 microM, respectively. They were similarly potent against NMDA induced currents in hippocampal neurons - IC(50) values of 1.51, 3.06 and 2.20 microM, respectively. In line with their moderate affinity, all were voltage dependent (delta = 0.86, 0.96 and 0.89, respectively) and fast, open-channel blockers (k(on) 7.90, 1.70 and 2.60 x 10(4) M(-1) sec(-1), k(off) 0.13, 0.12 and 0.24 sec(-1), respectively). These compounds are also NMDA receptor antagonists in the CNS following systemic administration and have good therapeutic indices in a variety of in vivo behavioural models where glutamate is known to play a pivotal role. In view of their relatively low affinity and associated rapid kinetics, they should prove to be useful therapeutics in a wide range of CNS disorders. PMID- 17728998 TI - Screening for blunt cerebrovascular injury in trauma patients. PMID- 17728999 TI - Ultrasonography and core needle biopsy in the differential diagnosis of fibroadenoma and tumor phyllodes. AB - BACKGROUND: The diagnosis of phyllodes tumors of the breast is challenging due to many similarities with common fibroadenomas. PURPOSE: To determine the diagnostic accuracy of core needle biopsy in diagnosing phyllodes tumors and to analyze the ultrasonographic (US) features of phyllodes tumors and fibroadenomas. MATERIAL AND METHODS: From 1999 to 2003, 1010 breast lesions underwent imaging-guided core needle biopsy. Of these, 57 fibroadenomas and 12 phyllodes tumors were removed surgically. The US and needle biopsy results of a total of 64 lesions (52 fibroadenomas and 12 phyllodes tumors) were further analyzed, compared, and correlated with surgical histological results. RESULTS: The median sonographic sizes of the phyllodes tumors and the fibroadenomas were 3.2 cm and 1.6 cm, respectively. At US, 58% of the phyllodes tumors (7/12) were classified as equivocal or suspicious of malignancy and 42% (5/12) as probably benign, while 54% of the fibroadenomas (28/52) were classified as probably benign and 46% (24/52) as equivocal. The sensitivity, specificity, and positive and negative predictive values of core needle biopsy histology regarding tumor phyllodes were 83%, 92%, 71%, and 96%, respectively. CONCLUSION: Imaging-guided core needle biopsy was accurate in differentiating between fibroadenomas and phyllodes tumors. US classification was unreliable due to considerable overlap in the findings. Combined use of US feature analysis and needle biopsy may help to avoid the misinterpretation of phyllodes as fibroadenoma. PMID- 17729000 TI - Soft-copy reading in digital mammography of microcalcifications: diagnostic performance of a 5-megapixel cathode ray tube monitor versus a 3-megapixel liquid crystal display monitor in a clinical setting. AB - BACKGROUND: A recent study using dedicated contrast-detail phantoms showed that the image quality of a 3-megapixel (M) monitor can approach that of a 5M monitor in digital mammography. PURPOSE: To compare a 5M cathode ray tube (CRT) monitor with a 3M liquid crystal display (LCD) monitor for soft-copy reading of digital mammography of microcalcifications in a clinical setting. MATERIAL AND METHODS: 100 screen-detected microcalcification lesions (34 malignant and 66 benign) without mass that had been evaluated with 11-gauge stereotactic vacuum-assisted breast biopsy or definitive surgery were recruited into the study. One radiologist analyzed the soft-copy mammograms on a 5M CRT monitor and a 3M LCD monitor with 5 months between interpretations and scored the likelihood of malignancy and calcification distribution on a five-point scale. Calcification morphology and breast density were scored on a four-point scale. Positive predictive value (PPV) and negative predictive value (NPV) were calculated on the basis of a Breast Imaging Reporting and Data System. The interpretation time was also measured. RESULTS: There was no significant difference in the likelihood of malignancy (P = 0.655), calcification morphology (P = 0.168), calcification distribution (P = 0.11), and breast density (P = 0.0608). The PPV and NPV of soft copy reading on the 5M CRT monitor was 57% (30/53) and 91% (43/47), respectively, identical to the results using the 3M LCD monitor. The total interpretation time averaged 88 s for the 5M CRT monitor and 67 s for the 3M LCD monitor (P<0.0001). CONCLUSION: Soft-copy reading of a digital mammography of microcalcifications with a 3M LCD monitor was similar in diagnostic performance to a 5M CRT monitor in this study. PMID- 17729002 TI - Analysis of the origin of the right inferior phrenic artery in 178 patients with hepatocellular carcinoma treated by chemoembolization via the right inferior phrenic artery. AB - BACKGROUND: No previous report has described the level of the origin of the right inferior phrenic artery (RIPA) based on an analysis of the relationships between the level of the RIPA, the celiac artery (CA), the superior mesenteric artery (SMA), and the right renal artery (RRA) in a series of cases. PURPOSE: To evaluate the origin of the RIPA by retrospectively analyzing angiographic findings in 178 patients with hepatocellular carcinoma (HCC) who underwent transcatheter arterial chemoembolization (TACE) via the RIPA. MATERIAL AND METHODS: In patients treated with intraarterial chemoembolization for HCC, additional superselective chemoembolization of the RIPA branches was necessary in 178 cases. We analyzed the level of the origin of the RIPA in these patients according to the relationships between the level of the origin of the RIPA, the CA, the SMA, and the RRA on angiography. RESULTS: Among the 178 cases, the RIPA arose from 1) the aorta directly in 102 cases (57%), 2) the CA in 53 (30%), 3) the left gastric artery (LGA) in three (2%), 4) the dorsal pancreatic artery (DPA) in one (1%), and 5) the RRA in 19 (11%). The level of the origin of the RIPA that originated directly from the aorta was supraceliac in 56 cases (32%), between the CA and the SMA in 31 (17%), and between the SMA and the RRA in 15 (8%). CONCLUSION: In our study, the RIPA originated from the aorta between the CA and the SMA directly in 17% of cases. When it is difficult to identify the origin of the RIPA, we must keep in mind that the RIPA may originate from the right part of the aorta within the small distance between the SMA and the CA. PMID- 17729001 TI - Acceleration of primary liver tumor growth rate in embolized hepatic lobe after portal vein embolization. AB - BACKGROUND: Portal vein embolization (PVE) is now widely accepted as a useful preoperative procedure in selected patients undergoing extended hepatectomy. However, the effect of PVE on the growth of liver tumors has not been fully elucidated. PURPOSE: To retrospectively evaluate the effects of PVE on the growth of liver tumors in the embolized lobes. MATERIAL AND METHODS: Eight patients with a primary liver tumor, six hepatocellular carcinomas (HCC) and two cholangiocellular carcinomas (CCC), were studied. The growth rates of the tumors in the embolized lobes and non-embolized liver parenchyma were calculated using the computed tomography (CT) volume values at the time of tumor identification, and before and after PVE. RESULT: The median tumor growth rate was 0.59 cm(3)/day (range 0.22-6.01 cm(3)/day) before PVE and 2.37 cm(3)/day (range 0.29-13.97 cm(3)/day) after PVE (P = 0.018). The tumor growth acceleration ratios ranged from 1.50 to 7.46 (median 2.65) in the six HCCs, and were 1.00 and 1.32 in the two CCCs. There was no apparent correlation between the tumor growth rate after PVE and the growth rate of non-embolized liver parenchyma (median 6.00 cm(3)/day, range 1.24-11.0 cm(3)/day). CONCLUSION: Liver tumor growth in an embolized lobe accelerates after PVE, in patients with HCC. PMID- 17729003 TI - Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma by placing a temporary catheter via the subclavian route. AB - BACKGROUND: A permanent reservoir implantation is considered mandatory for hepatic arterial infusion chemotherapy (HAIC) of hepatocellular carcinoma (HCC). Since treatment sessions of HAIC may be limited for these end-staged patients, a simple alternative technique for this treatment is desirable. PURPOSE: To evaluate the feasibility of placing a temporary catheter for HAIC in advanced HCC patients. MATERIAL AND METHODS: 25 advanced HCC patients underwent HAIC with drugs delivered from a temporary catheter which was placed percutaneously by puncturing the left subclavian artery under ultrasound guidance. A course of chemotherapy consisted of five consecutive daily infusions of 5-fluorouracil, cisplatin, mitomycin C, and leucovorin. The catheter was removed on the 6th day. Therapy was repeated every 4-6 weeks with maximal number of courses of up to six. The total courses of HAIC in each patient, the catheter-placed-related complications, tumor response rate, and median survival of the patients were registered. RESULTS: A total of 77 courses of HAIC were performed with 100% technical success of catheter placement (1-6 courses in each patient, average 3.1 courses). The overall response rate was 20%, with complete response in two patients and partial response in three patients. Eleven (55%) of the 20 non responders died within 5 months (mean HAIC, two courses). None of the patients experienced complications such as catheter occlusion, hepatic arterial thrombosis, cerebral infarction, or local infection. CONCLUSION: With fewer catheter-related complications, HAIC by temporary catheter placement via subclavian puncture could be a treatment option. PMID- 17729005 TI - Ultrasound guidance for puncture and injection in the radiocarpal joint. AB - BACKGROUND: The use of intra-articular contrast agent has been shown to increase the diagnostic accuracy of wrist magnetic resonance (MR) in patients with suspected trauma of the wrist ligaments. Traditionally, the contrast agent has been applied under fluoroscopic guidance. PURPOSE: To present a method based on ultrasound guidance for the injection of intra-articular contrast agent in wrist MR. MATERIAL AND METHODS: One hundred eight patients (56 female and 52 male, mean age 36 years) referred for wrist MR arthrograms due to suspected ligament rupture were included in this retrospective study. The preferred injection point is about 1 cm distal to Lister's tubercle in the distal radius. A correct positioning of the injection needle can be ensured using ultrasound guidance. RESULTS: Using this technique, the injection was intra-articular in 93.5% of the 108 injections over a 2-year learning period. CONCLUSION: Ultrasound guidance of the contrast injection in radiocarpal MR arthrograms is a cost-effective and safe alternative to fluoroscopically guided procedures. Furthermore, the use of ultrasound guidance provides clues about possible fluid collections within the joint. PMID- 17729004 TI - Is subcutaneous local anesthesia in shoulder magnetic resonance arthrography necessary? AB - BACKGROUND: Magnetic resonance arthrography is a well-established diagnostic method in degenerative and traumatic disorders of the shoulder. Some radiologists prefer to apply a local anesthetic to the skin prior to performing the joint puncture. However, no information regarding the efficacy of local anesthetics exists. PURPOSE: To assess patient discomfort in arthrography injection. MATERIAL AND METHODS: A patient survey (n = 74) utilizing a visual analog scale (VAS) measured the intensity of pain in arthrography injection by those receiving local anesthetics (n = 36) versus those who did not (n = 38). RESULTS: Mean VAS scores were 20.8 (median 10.5, SD 24.3) for those receiving local anesthetics versus 19.3 (median 13.0, SD 20.7) for those who did not (P = 0.83, Mann-Whitney U test). CONCLUSION: Routine use of local anesthesia of the skin in arthrography injection is unnecessary. PMID- 17729006 TI - Intra- and interobserver reproducibility of vertebral endplate signal (modic) changes in the lumbar spine: the Nordic Modic Consensus Group classification. AB - BACKGROUND: The lumbar vertebral endplate is considered a potential cause of specific low back pain. However, in relation to future research, there is need for a reliable and detailed magnetic resonance imaging (MRI) protocol to be used in the evaluation of vertebral endplate signal changes. PURPOSE: To assess the intra- and interobserver reliability of the "Nordic Modic classification" protocol. MATERIAL AND METHODS: MRI scans of 50 individuals representative of the general Danish population aged 40 were evaluated by two observers. Criteria for grading the changes were developed by the Nordic Modic Consensus Group. After consensus was established, all 50 MRI examinations were evaluated independently by each observer. Intraobserver reliability was assessed by re-evaluation of the 50 examinations by one of the observers. Kappa statistics were used to calculate agreement. RESULTS: Intra- and interobserver agreement of the evaluation of variables describing vertebral signal changes, i.e. Modic type, location, volume, maximum height, and endplate area, were all found to have substantial to almost perfect agreement. The evaluation of osteophytes was found to be reliable, whereas the evaluation of localized endplate defects and irregular endplates had only moderate agreement. The evaluation of development over time was found to have substantial intraobserver agreement but only moderate interobserver agreement. As expected, intraobserver agreement was generally better than interobserver agreement. CONCLUSION: In this study, we found convincing reproducibility of a detailed evaluation protocol of vertebral endplate signal changes, the "Nordic Modic Classification." The authors recommend that the evaluation protocol should be used in future studies investigating vertebral endplate signal changes. PMID- 17729007 TI - Brain magnetic resonance imaging does not contribute to the diagnosis of chronic neuroborreliosis. AB - BACKGROUND: Borrelia infections, especially chronic neuroborreliosis (NB), may cause considerable diagnostic problems. This diagnosis is based on symptoms and findings in the cerebrospinal fluid but is not always conclusive. PURPOSE: To evaluate brain magnetic resonance imaging (MRI) in chronic NB, to compare the findings with healthy controls, and to correlate MRI findings with disease duration. MATERIAL AND METHODS: Sixteen well-characterized patients with chronic NB and 16 matched controls were examined in a 1.5T scanner with a standard head coil. T1- (with and without gadolinium), T2-, and diffusion-weighted imaging plus fluid-attenuated inversion recovery (FLAIR) imaging were used. RESULTS: White matter lesions and lesions in the basal ganglia were seen in 12 patients and 10 controls (no significant difference). Subependymal lesions were detected in patients down to the age of 25 and in the controls down to the age of 43. The number of lesions was correlated to age both in patients (rho = 0.83, P<0.01) and in controls (rho = 0.61, P<0.05), but not to the duration of disease. Most lesions were detected with FLAIR, but many also with T2-weighted imaging. CONCLUSION: A number of MRI findings were detected in patients with chronic NB, although the findings were unspecific when compared with matched controls and did not correlate with disease duration. However, subependymal lesions may constitute a potential finding in chronic NB. PMID- 17729008 TI - Determination of the effect of a single hemodialysis session on retrobulbar blood hemodynamics by color Doppler ultrasonography. AB - BACKGROUND: Retrobulbar hemodynamic alterations can occur during hemodialysis sessions, and patients with chronic renal failure may experience visual problems. PURPOSE: To evaluate the effect of single-session hemodialysis on retrobulbar vessel hemodynamics by color Doppler ultrasonography. MATERIAL AND METHODS: Thirty-five patients were included in the study. Retrobulbar blood flows were examined before and after dialysis sessions. Doppler spectral patterns of retrobulbar blood flow were evaluated. The t test for paired samples and the Wilcoxon matched-pairs signed-rank test were used for comparing the flow values before and after dialysis. RESULTS: Systolic and diastolic blood flow velocities of the ophthalmic artery, central retinal artery, central retinal vein, nasal posterior ciliary artery, and temporal posterior ciliary artery were found to be decreased bilaterally after hemodialysis sessions. No significant change was observed in resistivity index values after hemodialysis sessions. CONCLUSION: Our findings reveal that retrobulbar circulation was disturbed after a single hemodialysis session. PMID- 17729009 TI - Diffusion-weighted magnetic resonance imaging of cerebrospinal fluid in patients with and without communicating hydrocephalus. AB - BACKGROUND: Recent concepts about cerebrospinal fluid (CSF) circulation in communicating hydrocephalus (CoHy), which is also termed "restricted arterial pulsation hydrocephalus," suggest reduced arterial pulsations of subarachnoid vessels with a smaller amount of CSF shifted in subarachnoid spaces during the early systole. The postulated restriction of subarachnoid arterial pulsations in CoHy should induce a smaller motion artifact and reduced local stream effects in CSF in magnetic resonance (MR) diffusion-weighted imaging (DWI). PURPOSE: To investigate the maximum diffusivity in CSF in patients with and without CoHy using DWI. MATERIAL AND METHODS: 12 patients without CSF circulation disturbances and six cases with proven CoHy were assessed. Diffusion was measured in six non collinear directions without triggering the arterial pulse wave (scan time 6:45 min, voxel size 2x2x2 mm). Due to expected artifacts, the calculated maximum diffusivity was called apparent diffusivity. Regional high and low apparent diffusivity was assessed in CSF spaces on newly created 3D CSF motion maps. RESULTS: Patients with regular CSF circulation exhibited high apparent diffusivity in CSF in basal subarachnoid spaces, whereas apparent diffusivity was low there in patients with CoHy. CONCLUSION: DWI opens a feasible approach to study CSF motion in the neurocranium. Restricted arterial pulsations seem to be involved in CoHy. PMID- 17729010 TI - Treatment of acute ischemic brain infarction with the assistance of local intraarterial thrombolysis with recombinant tissue-type plasminogen activator. AB - BACKGROUND: Cerebral infarction is usually due to arterial occlusion. Prompt treatment with thrombolytic drugs can restore blood flow and improve recovery from an infarct. PURPOSE: To evaluate the clinical efficacy and safety of local intraarterial thrombolysis with recombinant tissue-type plasminogen activator (rtPA) in patients with acute middle cerebral artery (MCA) infarctions within 6 hours of the onset of symptoms. MATERIAL AND METHODS: Sixteen patients (10 females and six males) aged from 42 to 61 years, with acute MCA territory infarcts were selected for treatment with local i.a. rtPA up to 6 hours after the onset of symptoms. Patient selection was based on clinical examination, computed tomography (CT), and digital subtraction angiography (DSA). A clinical evaluation was performed before treatment, at the time of discharge, and 90 days post procedure on the basis of modified Rankin and NIHSS scores. Controls (n = 16, nine females and seven males) aged from 51 to 70 years were treated only with intravenous anticoagulation using i.v. heparin infusion. The control group was evaluated with multidetector CT (MDCT) angiography performed on entry to the study and at 2-4 hours afterwards. RESULTS: Eight patients (50%) achieved a modified Rankin score of 2 or less as the primary outcome after 90 days follow up. The secondary clinical outcome at 90-day follow-up was as follows: NIHSS score < or =1, three (19%) of the patients; NIHSS score > or =50% decrease, nine (56%) of the patients. A recanalization rate of 75% was achieved in 12 of the 16 treated patients, but only 12.5% in two of the 16 patients in the control group. Intracerebral hemorrhage occurred in two (12.5%) of the patients in the treatment group, but in only one patient (6%) in the control group. There were no deaths in the treated group after thrombolysis up to the time of discharge; however, during the 90-day follow-up, two patients died compared to three patients in the control group (19% vs. 12.5% mortality rate). CONCLUSION: Patients with cerebral infarction who were treated within 6 hours of onset using intraarterial rtPA thrombolysis had a significantly improved clinical outcome 90 days after the procedure compared to patients treated only with intravenous anticoagulation. PMID- 17729011 TI - Abnormal default-mode network activation in cirrhotic patients: a functional magnetic resonance imaging study. AB - BACKGROUND: Recently, increasing numbers of studies have demonstrated that, in humans, a default-mode functional network exists in the resting state. Abnormal default-mode network in various diseases has been reported; however, no report concerning hepatic cirrhosis has been published to date. PURPOSE: To prospectively explore whether the resting-state network in patients with hepatic cirrhosis is abnormal or not, using functional magnetic resonance imaging (fMRI). MATERIAL AND METHODS: 14 patients with hepatic cirrhosis (12 male, two female; 45+/-9 years) and 14 age- and gender-matched healthy volunteers (12 male, two female; 42+/-10 years) participated in a blocked-design fMRI study. A modified Stroop task with Chinese characters was used as the target stimulus. Statistical Parametric Mapping 99 software was employed to process the functional data. Individual maps and group data were generated for patients with hepatic cirrhosis and for healthy controls, respectively. Intergroup analysis between patients and healthy controls was also generated using the two-sample t-test model. Cluster analyses were done based on the group data, and an identical P value < or =0.01 with continuously connected voxels of no less than 10 was defined as significant deactivation. After fMRI scanning was complete, behavioral Stroop interference tests were performed on all subjects; reaction time and error number were recorded. RESULTS: Functionally, deactivation of the posterior cingulate cortex (PCC) and precuneus was absent when subjects performed the incongruous word reading task; deactivation of the PCC, precuneus, and ventral medial prefrontal cortex was increased when they performed the incongruous color-naming task. CONCLUSION: The functional as well as behavioral data suggest that cirrhotic patients may have an abnormal deactivation mode. The absence of deactivation in the PCC and precuneus may be a sensitive rather than specific marker in patients with hepatic cirrhosis. PMID- 17729012 TI - Preliminary study of hemodynamics in human carotid bifurcation by computational fluid dynamics combined with magnetic resonance angiography. AB - BACKGROUND: A longstanding hypothesis that correlates fluid dynamic forces and atherosclerotic disease has led to numerous analytical, numerical, and experimental studies over the years because it is very difficult to measure the hemodynamic variables of blood in vivo. PURPOSE: To investigate the technique of visualization and quantitation of hemodynamic variables at carotid artery bifurcation in vivo by combining computational fluid dynamics (CFD) and vascular imaging. MATERIAL AND METHODS: Twenty-six healthy volunteers underwent magnetic resonance (MR) angiography of the bilateral carotid artery by a 3.0T whole-body scanner. Hemodynamic variables at these carotid bifurcations were calculated and visualized by combining vascular imaging post-processing and CFD. RESULTS: The average velocity of the carotid bifurcation in the systolic phase and the diastolic phase was 0.46+/-0.24 m/s and 0.23+/-0.05 m/s, respectively. Eddy current and back flows were observed at bifurcation and the lateral part of the proximal internal carotid arteries (ICA) and external carotid arteries (ECA), and the shapes of them changed with phases of the cardiac cycle, which were significant at the middle of the systolic phase and faded out quickly downstream of the ICA and ECA. The average range of wall shear stress (WSS) at the bifurcation was 4.36+/-1.32 Pa, and the maximum WSS was 18.02+/-4.11 Pa. The WSS map revealed a large region of low WSS at the carotid bulb and extended to the outer wall in the proximal end of the ICA (the lowest value was below 0.5 Pa), and there was also a small region of low WSS at the outer wall in the proximal end of the ECA. CONCLUSION: CFD combined with vascular imaging can calculate and visualize hemodynamic variables at carotid bifurcation in vivo individually. PMID- 17729013 TI - Screening for carotid injury in trauma patients: image quality of 16-detector-row computed tomography angiography. AB - BACKGROUND: The introduction of multidetector-row computed tomography (MDCT) has revolutionized the initial management of multiply injured patients. This technology has the potential to improve the imaging of traumatic vascular injuries. PURPOSE: To evaluate the quality of multidetector-row computed tomography angiography (MDCTA) of the carotid arteries in the setting of a routine whole-body trauma scan. MATERIAL AND METHODS: 87 trauma patients underwent a routine whole-body CT scan in a 16-detector-row scanner including an MDCTA with a reconstructed axial slice thickness of 3 mm. Images were reviewed by three experienced radiologists with emphasis on image quality. Contrast density, severity, and origin of artifacts and the occurrence of vessel lesions were assessed for different vessel segments. RESULTS: 3642 separate vessel segments were evaluated. Contrast density was rated good or sufficient for diagnosis in 99.8%. A total of 67.3% of vessel segments were free of artifacts, while 27.9% of vessel segments showed minor artifacts not impairing diagnostic evaluation. Clinically relevant artifacts obscuring a vessel segment occurred in 4.7% and were mostly caused by dental hardware. Four dissections of the internal carotid artery were diagnosed by all three radiologists. CONCLUSION: As a rapid screening test for blunt carotid artery injury, integration of MDCTA in the routine imaging workup of trauma patients utilizing a whole-body CT trauma scan is possible and practicable. Image quality is mostly sufficient for diagnosis, but impaired in a few cases by artifacts deriving primarily from dental hardware. PMID- 17729015 TI - Radiological findings of primary retroperitoneal Ewing sarcoma. AB - Ewing sarcomas are most commonly located in bone, while extraskeletal involvement of the retroperitoneum is extremely rare. We describe the radiologic and pathological findings in an adult patient with retroperitoneal extraskeletal Ewing sarcoma. PMID- 17729014 TI - The place of computed tomography as a guidance modality in percutaneous nephrostomy: analysis of a 10-year single-center experience. AB - BACKGROUND: Percutaneous nephrostomy (PCN) has been established as an effective technique for urinary decompression or diversion. This procedure may be performed with the guidance of fluoroscopy, ultrasonography, a combination of fluoroscopy and ultrasonography, computed tomography (CT), or magnetic resonance imaging. PURPOSE: To retrospectively review experience with CT-guided PCN over a 10-year period in a single center. MATERIAL AND METHODS: All CT-guided PCN procedures performed in adults at our institution between 1995 and 2005 were evaluated. In 882 patients, 1113 nephrostomy catheters were inserted. Interventional radiologists or radiology residents under direct attending supervision inserted all catheters. During the PCN procedure, bleeding, sepsis, and injuries to adjacent organs were regarded as major complications. Clinical events requiring nominal therapy with no sequelae were regarded as minor complications. RESULTS: PCN procedures were performed via 1-3 punctures in patients with grades 0-1 and 2 hydronephrosis, and via 1-2 punctures in patients with grade 3 hydronephrosis. They were carried out with a procedure time ranging from 9 to 26 min. All PCNs were considered as technically successful, and no major complications were observed. There were minor complications including transient macroscopic hematuria (28.6%, 19.9%, and 4.9% in patients with hydronephrosis grades 0-1, 2, and 3, respectively) and perirenal hematomas in a total of eight patients. No patient required additional intervention secondary to complications of the PCN procedure. CONCLUSION: CT-guided PCN is an efficient and safe procedure with major and minor complication rates below the accepted thresholds. It can be used for the management of patients requiring nephrostomy insertion in inpatient settings, and might be a preferable procedure in patients with minimal or no dilatation of the renal pelvis. PMID- 17729016 TI - Modafinil augmentation of selective serotonin reuptake inhibitor therapy in MDD partial responders with persistent fatigue and sleepiness. AB - BACKGROUND: Partial response, no response, or residual symptoms following antidepressant therapy is common in clinical psychiatry. This study evaluated modafinil in patients with major depressive disorder (MDD) who were partial responders to adequate selective serotonin reuptake inhibitor (SSRI) therapy and excessive sleepiness and fatigue. METHODS: This retrospective analysis pooled the data of patients (18-65 yrs) who participated in two randomized, double-blind, placebo-controlled studies of modafinil (6-week, flexible-dose study of 100-400 mg/day or 8-week, fixed-dose study of 200 mg/day) plus SSRI therapy. Patients (n=348) met criteria for several residual symptoms (Epworth Sleepiness Scale [ESS] score>or=10; 17-item Hamilton Depression Scale [HAM-D] score between 4 and 25; and Fatigue Severity Scale [FSS] score>or=4). RESULTS: Compared to placebo, modafinil augmentation rapidly (within 1 week) and significantly improved overall clinical condition (Clinical Global Impression-Improvement), wakefulness (ESS), depressive symptoms (17-item HAM-D), and fatigue (FSS) (p<.01 for all). At final visit, patients receiving modafinil augmentation experienced statistically significant improvements in overall clinical condition, wakefulness, and depressive symptoms. Modafinil was well tolerated in combination with SSRI. CONCLUSIONS: Results of this pooled analysis provide further evidence suggesting that modafinil is an effective and well-tolerated augmentation therapy for partial responders to SSRI therapy, particularly when patients continue to experience fatigue and excessive sleepiness. PMID- 17729018 TI - Chronic painful physical conditions, disturbed sleep and psychiatric morbidity: results from an elderly survey. AB - BACKGROUND: The main purpose of this study is to investigate the association of disturbed sleep, chronic physical pain and psychiatric morbidity in people aged 60 years and over. METHODS: A population-based random sample of 7040 household residents aged 60 years and over, was examined in a face-to-face interview. Painful medical conditions were assessed through questions evaluating medical treatment, hospitalizations, and consultations for medical problems. Disturbed sleep was assessed through questions concerning the presence of sleeping problems in the past 4 weeks. RESULTS: The overall prevalence of disturbed sleep is 33.7% (95% CI: 32.5-34.8) and the 6-month prevalence of any chronic pain was 76.2% (95% CI: 74.2-78.2%). A substantial burden of disturbed sleep is associated with the presence of physical pain morbidity, 42.5% for back pain to 49.7% for headaches. The prevalence of pain among persons with disturbed sleep ranges from 25.8% for gastrointestinal pain to 54.6% for joint pain. The presence of comorbid pain and disturbed sleep has an important disability impact as assessed by socioecomomic/professional data, health care utilization, self-rated health and physical activity. In logistic regression models, headaches, psychiatric morbidity, rural origin, Caucasians, self-rated health and number of chronic pain conditions were significantly associated with disturbed sleep after controlling for demographic variables and comorbidities. Age has a negative effect on sleep complaints. CONCLUSIONS: Disturbed sleep is highly comorbid with other pain conditions particularly headaches and psychiatric morbidity in later life. The combination of pain and disturbed sleep leads to important role disability and increased utilization of medical services. PMID- 17729019 TI - Pharmacotherapy with atomoxetine for US children and adolescents. AB - BACKGROUND: Atomoxetine, a non-stimulant medication, was approved for treatment of Attention Deficit/ Hyperactivity Disorder (ADHD) in 2002. However, there is a paucity of recent practice-based national data on the use of atomoxetine. This article compares the use of atomoxetine with that of stimulant medications in outpatient treatment of U.S. children and adolescents, and examines the predictors of atomoxetine use in this population. METHODS: The 2003-2004 National Ambulatory Medical Care Survey and the outpatient department portion of the 2003 2004 National Hospital Ambulatory Medical Care Survey were used to determine the utilization of atomoxetine and stimulants in youth<20 years. Bivariate analyses were used to examine the use of atomoxetine relative to that of stimulant medications in children and adolescents (n=1,133). Multiple logistic regression analysis was applied to visits involving youths with ADHD to examine predictors of atomoxetine use (n=1,361). RESULTS: An estimated 14.51 million visits involving psychotropic agents resulted in prescription of atomoxetine and stimulants during the years 2003 and 2004. The percentage of visits for atomoxetine, as a proportion of all psychotropic visits, was nearly 10% (versus 40% for stimulants). Analyses of visits involving atomoxetine and stimulants revealed age- and region-based differences in the use of atomoxetine. Among children with ADHD, approximately 15% of outpatient visits resulted in prescription of atomoxetine; and stimulant medications were prescribed in nearly 61% of these visits. Examination of predictors of ADHD treatments (atomoxetine vs. stimulants) revealed no variations in the use of atomoxetine across sex, race, psychiatric comorbidity, primary care status, and metropolitan location. However, atomoxetine was preferred in 10-to-14 year old children, and in patients with private insurance. Physicians in the Northeast region were less likely to prescribe atomoxetine than physicians in the South. CONCLUSIONS: Although stimulant drugs remain the most frequently prescribed class of psychotropic medications for ADHD in children and adolescents, atomoxetine has emerged as the leading stimulant alternative. Preferential use of atomoxetine in age group 10-to 14 years needs to be further evaluated. Additionally, the role of several factors, including patient preferences, physician-related factors, and psychiatric comorbidity warrant further investigation. Data on differential safety and efficacy of atomoxetine and stimulants are needed to optimize pharmacotherapy in children. PMID- 17729017 TI - Conduct disorder subtype and comorbidity. AB - BACKGROUND: Conduct disorder is considered difficult to treat, but comorbid psychiatric disorders may be a basis for treating some youths with conduct disorder. We sought to identify patterns of comorbid psychiatric diagnoses and psychopathology associated with conduct disorder by reported age-of-onset. METHODS: Referred children and adolescents, aged 4-17 years old, were clinically evaluated. Ages of onset of CD symptoms (N=53) were ascertained and divided according to DSM-IV criteria as childhood onset (<10 years old) or adolescent onset (>or=10 years old). RESULTS: Childhood-onset conduct disorder was associated with higher rates of ADHD and anxiety disorders, male gender, and perceived and total hostility scores than adolescent-onset conduct disorder. Adolescent-onset was associated with higher rates of PTSD, alcohol and substance use disorders, complex comorbidity (i.e., 6+ diagnoses lifetime), and female gender. CONCLUSIONS: Understanding age-of-onset-related patterns of comorbidity may facilitate psychiatric treatment planning in children and adolescents with conduct disorder. PMID- 17729020 TI - A comparison of quality of life and psychosocial functioning in obsessive compulsive disorder and body dysmorphic disorder. AB - BACKGROUND: Obsessive-compulsive disorder (OCD) and body dysmorphic disorder (BDD) are possibly related disorders characterized by poor functioning and quality of life. However, few studies have compared these disorders in these important domains. METHODS: We compared functioning and quality of life in 210 OCD subjects, 45 BDD subjects, and 40 subjects with comorbid BDD+OCD using reliable and valid measures. RESULTS: OCD and BDD subjects had very poor scores across all measures, with no statistically significant differences between the groups. However, comorbid BDD+OCD subjects had greater impairment than OCD subjects on 11 scales/subscales, which remained significant after controlling for OCD severity. Comorbid BDD+OCD subjects had greater impairment than BDD subjects on 2 scales/subscales, which were no longer significant after controlling for BDD severity, suggesting that BDD severity may have accounted for greater morbidity in the comorbid BDD+OCD group. CONCLUSIONS: Functioning and quality of life were poor across all three groups, although individuals with comorbid BDD+OCD had greater impairment on a number of measures. It is important for clinicians to be aware that patients with these disorders--and, in particular, those with comorbid BDD and OCD--tend to have very poor functioning and quality of life across a broad range of domains. PMID- 17729021 TI - The efficacy and tolerability of duloxetine in the treatment of anxious versus non-anxious depression: a post-hoc analysis of an open-label outpatient study. AB - BACKGROUND: This study compares the efficacy and tolerability of 12 weeks of open label duloxetine in adult outpatients with anxious versus non-anxious depression. METHODS: Participants in a major depressive episode (N=249) began duloxetine treatment at 30 or 60 mg daily for the first week, followed by up to 11 weeks of flexibly dosed duloxetine (60, 90, or 120 mg daily). Efficacy measures included HAMD17, HAMA, and CGI-S. Safety and tolerability were assessed by early discontinuation and adverse event rates. Anxious depression was defined by a HAMD17 Anxiety/Somatization Factor score>or=7. RESULTS: Duloxetine treatment was associated with a significantly greater reduction in total HAMD17 scores and HAMD17 Anxiety/Somatization Factor scores among patients with anxious depression compared to non-anxious depression. Differences in CGI-S and HAMA scores at the end of the trial between groups were not statistically significant. Remission and response rates at endpoint were similar between groups, but anxious depressives had a significantly shorter median time to response. Discontinuation rates due to any reason, discontinuation due to adverse events, and treatment-emergent adverse events were similar between groups, except for the significantly greater occurrence of influenza in anxious depressives. CONCLUSIONS: Duloxetine's efficacy in anxious depression was somewhat superior to non-anxious depression; tolerability was comparable between groups. PMID- 17729022 TI - Is tiagabine helpful in generalized anxiety disorder? PMID- 17729023 TI - The treatment of psychogenic excoriation and obsessive compulsive disorder using aripiprazole and fluoxetine. PMID- 17729024 TI - Prolonged hypotension due to deliberate trazodone overdose in the presence of fluoxetine. PMID- 17729032 TI - Signal transduction and autoimmunity: introduction. PMID- 17729033 TI - TIM family proteins and autoimmunity. AB - Despite their relative novelty, a growing body of literature now demonstrates that T cell immunoglobulin and mucin domain (TIM) family proteins are important regulators of immunity. Not surprisingly, these proteins also play prominent roles in the control of auto-reactive immune responses. Thus, modulation of TIM protein function may prove to be a useful strategy to control autoimmune diseases. PMID- 17729035 TI - Multiple paths to loss of anergy and gain of autoimmunity. AB - B cells and autoimmunity: cells of the immune system have the capacity to recognize/neutralize a myriad array of disease-causing pathogens, while simultaneously minimizing damage to self tissue. Obvious breakdowns in this ability to distinguish between self and non-self are evident in multiple forms of autoimmune disease, where B and T cells mount damaging attacks on cells and organs. B cells may directly damage tissue by producing pathogenic antibodies that bind self antigen, fix complement or form immune complexes. Recent evidence also suggests B cells indirectly induce autoimmunity by concentrating low avidity self antigen through the B cell receptor and presenting self-peptides to autoreactive T cells. B cells may also initiate autoimmunity when provided sufficient help from autoreactive T cells that have escaped deletion in the thymus. Here, we will review the role of anergy in maintenance of tolerance and how alterations in the normal balance of positive and negative signals may contribute to the development of autoimmune disease in mouse models and humans. PMID- 17729034 TI - FcgammaRIIB as a modulator of autoimmune disease susceptibility. AB - Antibodies are secreted to recognize and in some cases directly neutralize pathogens. Another important means by which they are essential components of the immune system is through binding to Fc receptors. Effector responses triggered by antibody binding of Fc receptors affect a host of important cellular responses such as phagocytosis, inflammatory cytokine release, antigen presentation, and regulation of humoral responses. A crucial check on this antibody-mediated signal is through the inhibitory receptor, FcgammaRIIB. In this review we discuss how dysregulation of FcgammaRIIB can result in a lowered threshold for autoimmunity in mice and humans. We close with a discussion of the potential for applying these findings to immunotherapy. PMID- 17729036 TI - Adenosine and anergy. AB - T cells must integrate multiple environmental cues when deciding whether to mount an immunogenic or tolerogenic response. Since not all self-reactive T cells are eliminated during thymic development, mechanisms of peripheral tolerance such as T cell anergy contribute to preventing autoimmunity. Recent studies have implicated extracellular adenosine and the adenosine A(2A) receptor as playing an important role in inhibiting T cell effector function. Herein, we review the current literature regarding T cell anergy and the emerging literature implicating the A(2A) receptor as critical regulator of immune activation. Finally, we present evidence to suggest a possible role for adenosine A(2A) receptor signaling in T cell anergy. PMID- 17729037 TI - Role of phosphoinositide 3-kinase signaling in autoimmunity. AB - Activation of the phosphoinositide 3-kinase (PI3K) pathway promotes proliferation and survival in many different cell types of the immune system. PI3K acts downstream of receptors that mediate proliferation and survival in T cells, and required roles for individual class I PI3K catalytic isoforms have been established. Interestingly, mice with either augmented or diminished PI3K activity in T cells develop lymphoproliferation and signs of autoimmunity. Here, we summarize our current knowledge of mouse strains with hyperactive or reduced PI3K, different isoforms of class I PI3K in T cell-mediated immunity and autoimmunity, and the therapeutic implications for modulating this pathway for treatment of various autoimmune diseases. PMID- 17729038 TI - Apoptotic signal transduction and T cell tolerance. AB - The healthy immune system makes use of a variety of surveillance mechanisms at different stages of lymphoid development to prevent the occurrence and expansion of potentially harmful autoreactive T cell clones. Disruption of these mechanisms may lead to inappropriate activation of T cells and the development of autoimmune and lymphoproliferative diseases [such as multiple sclerosis, rheumatoid arthritis, lupus erythematosus, diabetes and autoimmune lymphoproliferative syndrome (ALPS)]. Clonal deletion of T cells with high affinities for self peptide-MHC via programmed cell death (apoptosis) is an essential mechanism leading to self-tolerance. Referred to as negative selection, central tolerance in the thymus serves as the first checkpoint for the developing T cell repertoire and involves the apoptotic elimination of potentially autoreactive T cells clones bearing high affinity T cell receptors (TCR) that recognize autoantigens presented by thymic epithelial cells. Autoreactive T cells that escape negative selection are held in check in the periphery by either functional inactivation ("anergy") or extrathymic clonal deletion, both of which are dependent on the strength and frequency of the TCR signal and the costimulatory context, or by regulatory T cells. This review provides an overview of the different molecular executioners of cell death programs that are vital to intrathymic or extrathymic clonal deletion of T cells. Further, the potential involvement of various apoptotic signaling paradigms are discussed with respect to the genesis and pathophysiology of autoimmune disease. PMID- 17729039 TI - Protein tyrosine phosphatase PTPN22 in human autoimmunity. AB - The discovery that a single-nucleotide polymorphism (SNP) in lymphoid tyrosine phosphatase (LYP), encoded by the PTPN22 gene, is associated with type 1 diabetes (T1D) has now been verified by numerous studies and has been expanded to rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), systemic lupus erythematosus, Graves' disease, generalized vitiligo and other human autoimmune diseases. In this paper, we discuss the association of PTPN22 with autoimmunity, the biochemistry of the PTPN22-encoded phosphatase, and the molecular mechanism(s) by which the disease-predisposing allele contributes to the development of human disease. PMID- 17729040 TI - Immune regulation by Foxo transcription factors. AB - The Foxo subfamily of forkhead (Fox) transcription factors are mammalian homologues of the Caenorhabditis elegans DAF-16 longevity gene, and play key roles in cellular and organism survival, death, proliferation and metabolism. A growing body of evidence indicates that Foxo proteins furthermore play critical roles in immune cell homeostasis, modulating inflammation in some disease states such as inflammatory arthritis and systemic lupus erythematosus (SLE), via fundamental roles in T cells, B cells, neurophils and other myeloid lineages. This review summarizes current knowledge of the Foxo family members in general and in immunity, including their potential use as therapeutic targets. PMID- 17729042 TI - Amantadine treatment following traumatic brain injury in children. AB - PRIMARY OBJECTIVE: The focus of this paper is to review the current literature on the use of amantadine in children who have sustained a head injury. MAIN OUTCOMES AND RESULTS: A MEDLINE search was conducted and yielded five papers. They were composed of prospective, retrospective and case study designs. Dosage use and side effect profiles were consistent with expected norms. Efficacy was measures primarily by alertness and arousal and positive results were found for all studies on these dimensions. Behavioural and cognitive measures of outcome yielded mixed results. CONCLUSIONS: The studies reviewed for this paper suggest that amantadine is clinically beneficial for children who have sustained head injuries. Double blind placebo controlled trials with larger sample sizes are needed to further substantiate these findings. PMID- 17729043 TI - Prevalence, characteristics and causes of aggressive behaviour observed within a neurobehavioural rehabilitation service: predictors and implications for management. AB - PRIMARY OBJECTIVE: To describe the characteristics and determinants of aggressive behaviour observed within a neurobehavioural unit. RESEARCH DESIGN: Statistical analysis of a database of routinely administered clinical measures, including the Overt Aggression Scale-Modified for Neurorehabilitation. METHODS AND PROCEDURES: Records of aggressive behaviour shown by 108 patients over 14 days were studied. Patient characteristics were also captured using 23 items from the Rehabilitation Institute of Chicago-Functional Assessment Scale. Four factors were identified: 'communication', 'cognition/function', 'neurobehavioural disability' and 'mood & self-esteem'. Relationships between patient characteristics, external factors and their interactions with aggression were examined. MAIN OUTCOMES AND RESULTS: Many (5548) episodes of aggression were recorded. Whilst most comprised verbal aggression, 729 physical assaults were made on others. Aggressive behaviour typically followed staff prompting or no obvious antecedent. Medical intervention was rare, most aggression was managed by staff not reinforcing this behaviour. Over 80% of physical assaults were made by people rated as having severe symptoms of neurobehavioural disability and poor communication. CONCLUSIONS: Neurobehavioural units require sufficient staff resources to engage patients in purposeful activities as these were associated with the least severe aggression. Despite increased OAS-MNR usage, a standardized methodology for investigating aggression is required to ensure compatibility between datasets. PMID- 17729041 TI - Regulation of dendritic cells by female sex steroids: relevance to immunity and autoimmunity. AB - Dendritic cells (DCs) are critical mediators of adaptive immunity, tolerance and autoimmunity. The human immune system exhibits sexual dimorphism, which is most evident in the female predominance of autoimmune diseases such as systemic lupus erythematosus (SLE). Female sex steroids are strongly implicated in mediating immune sexual dimorphism, in part because estrogen accentuates disease in several models of lupus autoimmunity. In contrast, progesterone may prevent disease development. While much investigation has focused on the effects of estrogen and progesterone on lymphocyte functions, far less attention has been paid to the effects of these hormones on DCs. Current evidence now indicates estrogen can activate DCs, while in contrast, progesterone inhibits DC functions. Thus, we hypothesize that the opposite effects these two hormones have on lupus autoimmunity reflect opposing effects on DC functions. Thus, through direct actions on DCs, female sex steroids may influence autoimmunity, immunity and tolerance. PMID- 17729045 TI - Being restricted in participation after a traumatic brain injury is negatively associated by passive coping style of the caregiver. AB - PURPOSE: To examine whether the caregivers' coping style is associated with the functional outcome of the traumatic brain injury (TBI) patient 1 year post injury. METHOD: A cross-sectional study among patients with a TBI, including their primary caregivers. The study included 51 patients aged 17-64 years with a moderate-to-severe TBI and 51 caregivers (23 parents and 28 partners) aged 23-67 years. The coping preferences of the caregivers were assessed at minimum 6 and maximum 12 months post-injury, by filling out the Utrecht Coping List (UCL) and were related to limitations in activity, as measured with the Frenchay Activities Index and with restrictions in participation as measured with the Sickness Impact Profile-68 of TBI patients 1 year post-injury. The patients were interviewed at their homes; the caregivers received and returned the UCL by mail. RESULTS: The patients' age and the caregivers' coping style are independently associated with restrictions in participation 1 year post-injury. CONCLUSIONS: A passive coping style of the primary caregiver is negatively associated with the patient's functional outcome in terms of participation in society. PMID- 17729044 TI - Treatment to improve self-awareness in persons with acquired brain injury. AB - AIM: To examine the effects of an awareness training protocol embedded within the practice of instrumental activities of daily living (IADLs) in participants with acquired brain injury on levels of self-awareness and functional performance. METHODS: This study used a randomized control trial design: 10 participants with moderate-to-severe brain injury received six sessions of the self-awareness training while they performed IADLs (experimental group) and 10 participants performed the same IADLs but received conventional therapeutic practice (control group). In the experimental group, participants were asked to predict their performance before each task performance and to estimate their performance level after the performance. OUTCOME MEASURES: Pre- and post-intervention outcome measures taken from the two groups were compared. Instruments were standardized measures of 'general' self-awareness with collateral reports by informants (e.g. Awareness Questionnaire); 'task-specific' self-awareness (e.g. Assessment of Awareness of Disability) and Self-Regulation Skills Inventory (SRSI). Performance on IADLs was assessed using the Assessment of Motor and Process Skills (AMPS). RESULTS: Compared to the control group, the intervention significantly improved IADL performances and self-regulation. No significant treatment effect was observed for task-specific self-awareness, general self-awareness or community integration. CONCLUSIONS: The self-awareness intervention significantly but selectively improved self-awareness during IADL task performance as well as functional performance. The need for a larger study with more treatment sessions is discussed. PMID- 17729046 TI - Community integration, social support and life satisfaction in relation to symptoms 3 years after mild traumatic brain injury. AB - PRIMARY OBJECTIVE: To investigate the relation between psychosocial functioning (community integration, life satisfaction and social support) and symptoms (post concussion, post-traumatic stress and depression) in persons with mild traumatic brain injury (MTBI) 3 years after the trauma. METHODS: Population-based follow-up study of 163 patients. At follow-up, an assessment of community integration, social support, life satisfaction and symptoms was made. RESULTS: Total score of Community Integration Questionnaire (CIQ) was negatively correlated to total score of the Rivermead Post-Concussion Symptoms Questionnaire (RPQ, r = -0.270, p < 0.001) and to total score of the Beck Depression Inventory (BDI, r = -0.332, p < 0.001). Life satisfaction (LiSat-11) was negatively correlated to the RPQ (r = 0.459, p < 0.001), to total score of the Impact of Event Scale (IES, r = -0.365, p < 0.001) and to the BDI (r = -0.642, p < 0.001). Low levels of life satisfaction were common at follow-up. CONCLUSIONS: A large proportion of the individuals with MTBI experienced both psychosocial difficulties, with low levels of life satisfaction in particular and symptoms (post-concussion, post-traumatic stress and depression) 3 years after trauma. Since the possibility of pre-injury factors contributing to the condition at follow-up cannot be ruled out, the study indicates that all these factors should be taken into consideration in the management of persons with MTBI. PMID- 17729047 TI - Applicability of neural reserve theory in mild traumatic brain injury. AB - OBJECTIVE: The aim of the current study was to examine whether neural reserve influenced the duration of post-traumatic amnesia (PTA) following mild traumatic brain injury (MTBI). METHOD: The relationship between duration of PTA and both IQ and education was examined in a group of 59 MTBI patients. In addition, the effects of factors that could potentially diminish neural reserve, namely pre injury hazardous alcohol consumption, pre-injury marijuana use, previous neurological damage, age and post-injury emotional distress on PTA duration were analysed. RESULTS: Significant, negative associations between PTA duration and both IQ and education were revealed. None of the other variables that were examined were significantly related to PTA duration. CONCLUSION: The findings were interpreted as providing preliminary evidence to suggest that reference to neural reserve may help explain between-subject variability in acute response to MTBI. PMID- 17729048 TI - The contribution of pre-existing depression to the acute cognitive sequelae of mild traumatic brain injury. AB - PRIMARY OBJECTIVE: To determine the effect of pre-existing depression on the cognitive sequelae of mild traumatic brain injury (mTBI) within 24 hours of injury. RESEARCH DESIGN: A 2 x 2 between-subjects design was used to examine the effect of depression and injury type on neuropsychological test performance. The independent variables were the injury type (mTBI or control) and the presence of depression (depressed or not depressed). METHODS AND PROCEDURES: Participants who had sustained mTBI (30 with depression, 30 without depression) within the previous 24 hours and control participants (19 with depression, 30 without depression) were assessed on the Digit Symbol Substitution Test (DSS), Hopkins Verbal Learning Test (HVLT) and the Speed of Comprehension Test. RESULTS: Participants with mTBI performed worse than controls on the tests, particularly HVLT delayed recall and DSS total correct. Participants with depression did not perform worse than participants without depression. However, there was a significant univariate interaction for HVLT recognition, participants who had sustained mTBI and were classified in the depressed group exhibited worse recognition compared to mTBI participants without depression. CONCLUSIONS: The results indicate that depression may interact with mTBI to impair word recognition during the acute phase after a head injury. PMID- 17729049 TI - Neuropsychological function 23 years after mild traumatic brain injury: a comparison of outcome after paediatric and adult head injuries. AB - PRIMARY OBJECTIVE: To the authors' knowledge no study comparing very long-term neuropsychological outcome after mild paediatric and adult traumatic brain injury (TBI) has been published. The primary objective of this study was to compare neuropsychological outcome 23 years after mainly mild paediatric and adult TBI. RESEARCH DESIGN: The study was a neuropsychological follow-up 23 years after a prospective head injury study conducted at a Norwegian public hospital. METHODS AND PROCEDURES: One hundred and nineteen patients were assessed with a comprehensive neuropsychological test battery. Of these, 45 were paediatric TBI and 74 were adult TBI. MAIN OUTCOMES AND RESULTS: Both the paediatric and adult groups obtained scores in the normal range. In the paediatric group significant relationships were found between head injury severity and current neuropsychological function. The most important predictors of poor outcome were length of post-traumatic amnesia (PTA) and a combination of PTA and EEG pathology within 24 hours of injury. No influence of pre- and post-injury risk factors on current neuropsychological function was evident. CONCLUSIONS: The findings indicate that children sustaining complicated mild TBI may be more vulnerable to development of chronic mild neuropsychological dysfunction than adults sustaining similar head injuries. PMID- 17729050 TI - Examining lactate in severe TBI using proton magnetic resonance spectroscopy. AB - PRIMARY OBJECTIVE: Clinical management of acute traumatic brain injury (TBI) has emphasized identification of secondary mechanisms of pathophysiology. An important objective in this study is to use proton magnetic resonance spectroscopy (pMRS) to examine early metabolic disturbance due to TBI. RESEARCH DESIGN: The current design is a case study with repeated measures. METHOD AND PROCEDURE: Proton magnetic resonance imaging was used to examine neurometabolism in this case of very severe brain trauma at 9 and 23 days post-injury. MRI was performed on a clinical 1.5 Tesla scanner. MAIN OUTCOMES AND RESULTS: These data also reveal that pMRS methods can detect lactate elevations in an adult surviving severe head trauma and are sensitive to changes in basic neurometabolism during the first month of recovery. CONCLUSIONS: The current case study demonstrates the sensitivity of pMRS in detecting metabolic alterations during the acute recovery period. The case study reveals that lactate elevations may be apparent for weeks after severe neurotrauma. Further work in this area should endeavour to determine the ideal time periods for pMRS examination in severe TBI as well as the ideal locations of data acquisition (e.g. adjacent or distal to lesion sites). PMID- 17729051 TI - Bone fractures in the long-term care of a patient in a vegetative state: a risk to conflicts. AB - PURPOSE: This case report shows how recurrent bone fractures can increase the tension in the relationship between family and caregivers in the long-term care of a patient in a vegetative state (VS). The aim of this report is to prevent conflict situations elsewhere by informing the family in time about the risk of fractures in a situation of severe osteoporosis. RESULTS: A second opinion and a density test of the bone contributed to the acceptance of the family of that risk in the daily nursing care, after all adjustments to prevent fractures and to adapt the environment were undertaken. CONCLUSIONS: The registration of immobility and the risk of fractures in the problem list is recommended, particularly in the emotional context of the long-term care of a vegetative state. This should be part of the multidisciplinary care plan, in which regular evaluations and communication with family are essential. PMID- 17729052 TI - Sudden death following periorbital pellet injury. AB - PURPOSE: To report an uneventful sudden death because of a periorbital pellet injury. METHOD: Review of autopsy findings. RESULTS: A 20-year-old hunter was shot accidentally during hunting. At autopsy, the body showed no significant injuries or deformity except for the pellet injuries and ecchymosis on the medial side of the left lower eyelid. Skull roentgenography located a pellet in the base of the cranium. Upon craniotomy, the cause of death was diagnosed as subarachnoidal haemorrhage due to incomplete basilar artery injury. The pellet entered through the medial cantus, passed through the inferior orbital fissure than the sphenooccipital junction and basilar artery and lodged in the pons. CONCLUSION: A-high index of suspicion is required in order to detect an intracranial extension in periorbital injuries. PMID- 17729053 TI - Reproducibility of morning blood pressure surge and its relation to blood pressure reactivity. AB - This study examined the stability of the morning blood pressure surge (MBPS) and its relation to blood pressure (BP) reactivity in untreated hypertensives. Thirty six participants completed a stress task at baseline. Ambulatory BP monitoring was carried out three times on a weekday. The MBPS demonstrated small reproducibility and large coefficient of variation. The MBPS correlated with nighttime BP (p = 0.001) but not morning BP or BP reactivity. Dippers had greater MBPS than did nondippers (p < 0.05). The MBPS provides distinct information that is different from the BP response to mental stress. PMID- 17729054 TI - A moderately high fat diet promotes salt-sensitive hypertension in obese zucker rats by impairing nitric oxide production. AB - The objective of this research was to examine the contribution of a moderately high fat (MHF) diet to the development of salt-sensitive hypertension in obese Zucker rats. Lean and obese Zucker rats were fed either a MHF diet or a diet of standard rat chow (control diet) for 10 weeks. From week 4 through week 10, the drinking water was supplemented with 1% NaCl. Blood pressure was measured weekly, and urinary excretion of nitric oxide metabolites (NO(x)) was determined at weeks 4 and 10. At week 10, renal nitric oxide synthase (NOS) activity was assessed in kidney homogenates. Blood pressures of obese, but not lean, rats on the MHF fat diet were significantly increased by salt-supplementation, whereas blood pressures of rats on the control diet were not appreciably affected. NO(x) excretion was increased in response to salt-supplementation in rats on the control diet, with the effect being particularly dramatic in obese rats. After salt-supplementation, NO(x) excretion by rats on the MHF diet was lower than rats on the control diet. In obese rats on the MHF diet, this decrease in NO production was accompanied by a reduction in renal NOS activity. These results indicate that obese rats are more inclined than lean rats to develop diet-induced hypertension in response to a moderately high fat, salt-supplemented diet. Furthermore, they suggest that MHF diet-induced defects in NO production may promote the salt-sensitivity of blood pressure in obese Zucker rats, which appear to require more NO to maintain blood pressure during a salt challenge. PMID- 17729056 TI - Does elevated high-sensitivity serum C-reactive protein associate with hypertension in non-obese Japanese males? AB - The object of this study is to assess whether elevated hsCRP levels are independently related to hypertension in non-obese Japanese males. This cross sectional study comprised 86 hypertensive and 109 normotensive subjects. We defined hypertension as a systolic blood pressure >/=140 mmHg and/or a diastolic blood pressure >/=90 mmHg and/or taking antihypertensive therapy. Log-hsCRP levels were significantly higher in hypertensive than normotensive subjects. In logistic regression analysis, subjects in the highest tertile had a two-fold higher risk than those in the lowest tertile. The association between hypertension and hsCRP levels was marginally significant. In addition, there was a significant tendency for hypertension to increase with an increase in CRP level (p < .05). These findings suggest that elevated hsCRP level is an independent risk factor for hypertension in non-obese Japanese males. PMID- 17729055 TI - Different effect of psyllium and guar dietary supplementation on blood pressure control in hypertensive overweight patients: a six-month, randomized clinical trial. AB - In the setting of a six-month, open-label clinical trial, 141 consecutively enrolled, hypertensive, overweight patients were randomized to the oral ingestion of psyllium powder or guar gum 3.5 gr t.i.d., to be taken 20 min before the main two meals, or to standard diet. Both fibers improved significantly BMI, FPG, FPI, HOMA Index, HbA1c, LDL-C, and ApoB. Psyllium supplementation only exerted a significant improvement in plasma TG concentration, in SBP and DBP. In our study, six-month supplementation with psyllium fiber, but not with guar fiber nor standard diet, appears to significantly reduce both SBP and DBP in hypertensive overweight subjects. PMID- 17729057 TI - Cardiovascular responses to somatosensory stimulation and their modulation by baroreflex mechanisms. AB - Exposure of experimental animals to noxious somatic stimulations sometimes induces sustained hypertension. Information regarding the medullary projections of somatic afferents and the neurotransmitters involved in them is incomplete. The present investigation in urethane-anesthetized, artificially ventilated, adult male Wistar rats was undertaken to clarify some of these issues. It was observed that the inhibition of contralateral, ipsilateral, or bilateral rostral ventrolateral medullary pressor area (RVLM) with muscimol attenuated the pressor and tachycardic responses to sciatic nerve stimulation. Similar inhibition of the medial subnucleus of the solitary tract (mNTS) exaggerated the cardiovascular responses to sciatic nerve stimulation. Interruption of the baroreflex by microinjections of ionotropic glutamate receptor antagonists into the mNTS or barodenervation also exaggerated the responses to sciatic nerve stimulation. Unilateral stimulation of the aortic nerve blocked the cardiovascular responses to the sciatic nerve stimulation. These results indicated that in the rat, the ascending afferents in the sciatic nerve project bilaterally to the RVLM as well as mNTS; an excitatory amino acid, probably glutamate, is released in the mNTS in response to the sciatic nerve stimulation; and barodenervation or blockade of baroreflex in the mNTS exaggerates, while baroreceptor stimulation inhibits, cardiovascular responses to somatosensory stimulation. PMID- 17729059 TI - Chronic effort dyspnea explained by lung function tests and by HRCT and CRX radiographic patterns in COPD: a post-hoc analysis in 51 patients. AB - This paper is a post-hoc analysis of a previous study performed to investigate the relationship between computerized tomography (CT) and lung function in 51 outpatients with mild-to-moderate COPD. We studied whether changes in lung function and radiographic patterns may help to explain dyspnea, the most disturbing symptom in patients with COPD. The Medical Research Council (MRC) dyspnea scale shows, by univariate analysis, a similar strength of association to CT expiratory lung density and to DL(CO), a functional index of lung parenchymal loss. The MRC dyspnea scale shows a somewhat less strength of association with a small vertical heart on plain chest films. In multivariate analysis, the model with the strongest association to the MRC dyspnea scale (r = 0.76, p < 0.0001) contains 4 explanatory variables (DL(CO), FRC, PaCO(2), and radiographic pattern of pulmonary hypertension). We suggest that diffusing capacity reflects the emphysematous component of hyperinflation, associated by definition with destruction of terminal airspace walls, as distinct from the air trapping component, which is ascribed to airway obstruction and associated with FRC. PaCO(2) mainly reflects the ventilatory components, i.e., ventilatory drive and ventilatory constraints, of pulmonary gas exchange in COPD, while radiographic pattern of pulmonary hypertension likely reflects hypoxic vascular changes, which depend mainly on ventilation/perfusion mismatch and give rise to pulmonary arterial hypertension that may contribute per se to dyspnea. In conclusion, our analysis points out that chronic effort dyspnea variance may account for up to 58% (r(2) = 0.58) by lung function tests and radiographic patterns. Thus, about 42% of the MRC dyspnea variance remains unexplained by this model. On the other hand, dyspnea ascertainment is dependent on subjective behavior and evaluation and in tests is influenced by individual performance and perception. For example in the 6-minute walk test, a similar or higher proportion (60%) of the overall variance is unexplained. PMID- 17729058 TI - Telmisartan in the treatment of Cohen-Rosenthal Diabetic Hypertensive rats: the benefit of PPAR-gamma agonism. AB - The antihypertensive and hypoglycemic effects of telmisartan, which has dual angiotensin II antagonist-PPAR-gamma agonist properties, was studied in Cohen Rosenthal Diabetic Hypertensive rats (CRDH), a model in which hypertension, insulin resistance, and diabetes co-exist. CRDH, Cohen-diabetic rats (CDR), and SHR received telmisartan (3 mg/kg/day in drinking water) for five months. Telmisartan significantly lowered systolic and diastolic BP in SHR and CRDH, independent of body weight, and remained fairly constant in controls throughout the experiment. Blood glucose levels fell rapidly in the treated animals and remained steady in controls. Results indicate that telmisartan is a prototype of a new approach to treating coexisting diabetes and hypertension. PMID- 17729060 TI - Investigating new standards for prophylaxis in reduction of exacerbations--the INSPIRE study methodology. AB - Bronchodilators, including long-acting beta(2)-adrenoceptor agonists and anticholinergic bronchodilators, are effective in the treatment of chronic obstructive pulmonary disease. Evidence suggests that the addition of a long acting beta(2)-agonist to an inhaled corticosteroid is associated with a reduced rate of exacerbations compared with either treatment alone or placebo. However, it is not known whether a long-acting beta(2)-agonist/inhaled corticosteroid combination is more effective than an anticholinergic bronchodilator alone in reducing exacerbations. The Investigating New Standards for Prophylaxis In Reduction of Exacerbations (INSPIRE) trial will study salmeterol (a long-acting beta(2)-agonist) in combination with fluticasone propionate (an inhaled corticosteroid) compared with tiotropium bromide (an anticholinergic bronchodilator) in patients with moderate-to-severe chronic obstructive pulmonary disease. The INSPIRE study is a multicentre, randomised, double-blind, double dummy, parallel group study conducted over 104 weeks. This is the first study to use two parallel definitions of an exacerbation; an event-based exacerbation is defined as one that requires use of healthcare resources, including additional treatment and hospitalization, whereas a symptom-based exacerbation is defined as one that satisfies the 1987 Anthonisen criteria. It is also the first study to compare the long-term effects of salmeterol/fluticasone propionate with tiotropium bromide on the rate of event-based exacerbations. Endpoints include rate of exacerbations (primary endpoint), time to first exacerbation, and duration of exacerbations. Health outcomes will be assessed via the St George's Respiratory Questionnaire. If the innovative methodology of utilizing 2 definitions of exacerbation proves successful, it will set the benchmark for future studies in chronic obstructive pulmonary disease. PMID- 17729061 TI - Is exercise important in chronic obstructive pulmonary disease? AB - Chronic obstructive pulmonary disease impairs the ability of patients to perform maximal physical exercise, particularly in patients with severe lung disease. However, differing perceptions of the meaning and importance of exercise to patients and caregivers is likely to impair patient-physician communication about current medical status and outcomes of therapeutic interventions. Other outcomes of importance to patients including actual performance of functional activity during daily life and health-related quality of life may also be affected by impaired exercise capacity. However, the relationships between exercise, activity, and quality of life are inconsistent. Thus, measurement of physiologic and patient-centered outcomes may provide the best approach to assessing responses to therapeutic interventions. These concepts were explored in a conference sponsored by Boehringer Ingelheim Pharmaceuticals, Inc. and Pfizer Inc and reviewed in the articles generated from the symposium in this issue of COPD. PMID- 17729062 TI - How can we assess outcomes of clinical trials: the MCID approach. AB - Interpreting changes in outcomes of clinical trials in chronic obstructive pulmonary disease should be viewed from a broader perspective than only the statistical significance of the findings. The minimal clinical difference in outcome measures provides a conceptual framework to assist in clinical trial interpretation and a methodology to assess the clinical relevance of study results. Use of distribution-based techniques, comparison with other external measures, and opinions from experts, clinicians and patients can assist in minimal clinically important difference development. Although the minimal clinically important difference has been suggested for a wide range of outcomes of importance in chronic obstructive pulmonary disease, many have not been subjected to rigorous analysis. For newer tools such as activity monitors and questionnaires and measures not widely employed such as laboratory-based exercise tests, minimal clinically important differences remain to be determined. PMID- 17729063 TI - Exercise capacity in chronic obstructive pulmonary disease: mechanisms of limitation. AB - Patients with chronic obstructive pulmonary disease (COPD) are often caught in a downward spiral that progresses from expiratory flow limitation to poor quality of life and invalidity. Within this downward spiral, exercise tolerance represents a key intermediate outcome. As recently stated by the GOLD initiative, improvement in exercise tolerance is now rec ognized as an important goal of COPD treatment. This objective will be achieved only by a comprehensive understanding of the mechanism of exercise limitation in this disease. The objective of this paper is to review the mechanisms of exercise limitation in COPD and discuss their relative contribution to exercise intolerance in patients suffering from this disease. PMID- 17729064 TI - The relationship between exercise tolerance and other outcomes in COPD. AB - Exercise training has been shown to be a clinically effective therapeutic intervention for COPD patients resulting in a myriad of beneficial effects. These include improvements in exercise tolerance, health-related quality of life and activity levels. Activity levels can be assessed using health-related quality of life instruments or instruments designed especially for this purpose. Previous studies show that the relationships between activities of daily living, assessed using generic health-related quality of life instruments, and exercise vary considerably with correlations ranging from 0.18-0.72. The relationships between activities of daily living, assessed using disease specific health-related quality of life instruments, and exercise also vary considerably with correlations ranging from 0.14-0.59. The relationships between activities of daily living, assessed using activities of daily living instruments, and exercise are less variable and generally stronger with correlations ranging from 0.34 0.83. Relationships between generic health-related quality of life instruments and exercise vary considerably (0.19-0.65) as do relationships between disease specific health-related quality of life instruments and exercise (0.18-0.61). The correlations between changes in activities of daily living and changes in exercise following pulmonary rehabilitation are generally weak (0.13-0.28). The correlations between changes in health-related quality of life and changes in exercise following pulmonary rehabilitation are also generally weak. The fact that these outcomes are not tightly associated is due, in part, to the variability in responses to the instruments used and the fact that the various instruments were often designed to assess different constructs. PMID- 17729065 TI - Field tests of exercise in COPD: the six-minute walk test and the shuttle walk test. AB - Exercise testing is useful to assess the degree of disability, prognosis for survival, presence of exercise-induced hypoxemia, and response to treatment in individuals with chronic obstructive pulmonary disease. Simple walking tests have been developed and are increasingly used in assessment of chronic obstructive pulmonary disease patients for clinical and research purposes. This article reviews how these tests are performed and to what degree they are reliable, and how these tests are used in assessment of individuals with chronic obstructive pulmonary disease. PMID- 17729066 TI - Dyspnea and activity limitation in COPD: mechanical factors. AB - Dyspnea and activity limitation are the primary symptoms of chronic obstructive pulmonary disease and progress relentlessly as the disease advances. In COPD, dyspnea is multifactorial but abnormal dynamic ventilatory mechanics are believed to be important. Dynamic lung hyperinflation occurs during exercise in the majority of flow-limited patients with chronic obstructive pulmonary disease and may have serious sensory and mechanical consequences. This proposition is supported by several studies, which have shown a close correlation between indices of dynamic lung hyperinflation and measures of both exertional dyspnea and exercise performance. The strength of this association has been further confirmed by studies that have therapeutically manipulated this dependent variable. Relief of exertional dyspnea and improved exercise endurance following bronchodilator therapy correlate well with reduced lung hyperinflation. The mechanisms by which dynamic lung hyperinflation give rise to exertional dyspnea and exercise intolerance are complex. However, recent mechanistic studies suggest that dynamic lung hyperinflation-induced volume restriction and consequent neuromechanical uncoupling of the respiratory system are key mechanisms. This review examines, in some detail, the derangements of ventilatory mechanics that are peculiar to chronic obstructive pulmonary disease and attempts to provide a mechanistic rationale for the attendant respiratory discomfort and activity limitation. PMID- 17729067 TI - Functional performance and physical activity in chronic obstructive pulmonary disease: theoretical perspectives. AB - Two paradigms are commonly used to evaluate the functional limitations and restrictions imposed by the progression of COPD. The disabilities paradigm serves as a tool to evaluate a patient's functional status and details methods of managing disabilities and the health and fitness paradigm quantifies fitness and promotes physical activity as a means of regaining health. Functional capacity and physical symptoms are the most important predictors of functional performance. The functional status and disabilities models have been effective in identifying predictors of functional capacity and functional performance and to describe the effects on pulmonary rehabilitation. The emphasis has been placed on functional capacity rather than preventing future comorbidities. It is possible, however, to make further gains in health by also emphasizing physical activity. The health and fitness paradigm for individuals with COPD distinguishes between the health benefits of physical activity and the health benefits of physical fitness. Linking the two paradigms may ultimately improve the health and functioning of people with COPD. PMID- 17729068 TI - Subjective measurement of activity in chronic obstructive pulmonary disease. AB - Activity is an essential part of life. Daily activities include caring for one's self and one's environment, moving about the home and community, and fulfilling various social roles. Personal fulfillment activities, such as interaction with others, hobbies, and attending social or entertainment events, play an important role in life satisfaction and well-being. Physical activity in the form of movement and exercise is essential for optimal fitness and health. Given these varied perspectives, what constitutes "activity" and how is it measured, both generally and in chronic obstructive pulmonary disease specifically? How should "activity" be measured as an outcome of treatment - pharmacologic, surgical, or rehabilitation? This paper discusses patient-reported measurement of activity, with specific reference to patients with chronic obstructive pulmonary disease. It begins with an overview of key measurement issues to consider when selecting or developing instruments, followed by clarification of two perspectives or classes of patient-reported activity assessment: functional and physical activity. Examples of measures designed to capture these concepts are provided. The paper concludes with recommendations for evaluating activity-related outcomes in patients with chronic obstructive pulmonary disease. PMID- 17729069 TI - Activity monitoring in assessing activities of daily living. AB - Individuals who have active lifestyles appear to reap substantial benefits. It is therefore of interest to assess level of activity and to determine whether interventions are capable of altering activities of daily life. Questionnaires are often employed because of their simplicity, but objective measures are sought. Long-term assessment of energy expenditure, either through doubly labeled water analysis or through measurements of expired gases are expensive and often impractical. Activity monitors include pedometers, heart rate monitors, accelerometers and integrated multisensor systems. Rapidly advancing activity monitor technology has enabled long-term use and facilitated downloading of recordings to computers where sophisticated analysis of activity patterns can be made. Accelerometer-based systems have received the most attention. When applied to chronic obstructive pulmonary disease patients, accelerometric monitors have demonstrated low levels of activity; those using long-term oxygen and those having exacerbations are particularly inactive. PMID- 17729070 TI - Limited functional performance in chronic obstructive pulmonary disease: nature, causes and measurement. AB - Patients with chronic obstructive pulmonary disease (COPD) frequently describe limitations in functional performance. These limitations predict mortality, adversely affect health-care burden and impair health-related quality of life. The optimal method for quantifying the functional performance in COPD subjects has not been established. This paper discusses the (i) nature of limited functional performance reported by individuals with COPD, (ii) mechanisms that contribute to these limitations, (iii) assessment techniques available to provide markers of functional performance and (iv) areas for further research in measuring functional performance of COPD subjects. PMID- 17729071 TI - Quality of life: concept and definition. AB - This paper will consider 4 topics: (1) the definition of health-related quality of life, (2) the measurement of health-related quality of life, (3) the relationship between exercise and health-related quality of life in the general population, and (4) the relationship between exercise and health-related quality of life in patients with COPD. The paper presents data from the National Health Interview Survey, the San Diego COPD Rehabilitation Trials, and the National Emphysema Treatment Trial (NETT). PMID- 17729072 TI - Activity limitation and quality of life in COPD. AB - Limitation of activity and impaired quality of life are important outcomes of COPD. There is an association between measures of self-reported physical activity and overall health status, and they appear to change together spontaneously over time and in response to treatment. The relationship between symptoms and activity limitation is complex, because activity can be limited entirely by symptoms, or impaired by symptoms so that it requires greater effort or causes discomfort. The patient has the choice of whether to restrict their activity or maintain it at the cost of having symptoms. In theory, this may make it difficult to produce reliable standardized assessments of activity limitation because it may not be clear exactly what is being measured. Analysis of items in the St George's Respiratory Questionnaire (SGRQ) concerned with activities that are either not possible due to breathlessness, or are a cause of breathlessness, show that they contribute to a unidimensional model of activity limitation in daily life and a unidimensional model of overall COPD-related health status. The items lie distributed evenly along the same severity continuum, from very mild to very severe, along with other items concerned with symptoms and the psycho-social impact of the disease. This suggests that self-reported limitation of activity may form a reliable construct, and may also provide a good surrogate marker of health status in COPD. PMID- 17729074 TI - COPD and exercise: what's really important? A nursing perspective. AB - Numerous studies demonstrate the importance of exercise training to improve endurance in patients with chronic obstructive pulmonary disease (COPD) and its positive effect on activities of daily living and quality of life. However, successful care of the individual with COPD also relies on recognizing that this person requires individualized care and non-pharmacologic modalities specific to their needs in order to cope with the various aspects of their disease. It is also important to note that improvement in quality of life is not necessarily related to improvement in exercise endurance alone. Comprehensive and effective pulmonary rehabilitation for the COPD patient needs to encompass several components to provide benefit for the spectrum of symptoms of COPD beyond exercise tolerance and dyspnea to ultimately improve quality of life. PMID- 17729073 TI - The impact of change in exercise tolerance on activities of daily living and quality of life in COPD: a patient's perspective. AB - Patient-centered outcomes are a critical goal in the management of COPD. This personalized patient account of living with COPD indicates the importance of health-related quality of life (HRQoL) when considering the profound impact of reduced exercise tolerance on activities of daily living. The recognition of breathlessness indicating damage to the lungs from smoking and exacerbations of dyspnea associated with activity avoidance sent this patient to her clinician for a diagnosis of COPD. The eventual acceptance of her condition led to her attendance in a pulmonary rehabilitation program that made a "tremendous difference" for both the exercise and the social support it offered, and it reinforced her determination to maintain her independence and mobility that seem to contribute to a positive attitude in dealing with this challenging disease. PMID- 17729076 TI - How are you doing? What are you doing? Differing perspectives in the assessment of individuals with COPD. AB - COPD exacerbations often lead to a downward spiral of physical activity. To compensate for the discomfort brought on by exertional dyspnea and the accompanying fatigue, patients with COPD will settle into a sedentary lifestyle that deconditions their bodies, serves to further aggravate breathlessness, and results in a further downward adjustment of physical activity. Progression of COPD imposes profound limitation on activities of daily living and gives rise to anxiety and depression. The distressing symptoms of breathlessness and the perception of these abnormalities by the patient lead to a reduction in health related quality of life. The clinician's therapeutic interventions have to address these symptom and activity limitations with the goal of improving the patient's quality of life. PMID- 17729075 TI - The impact of exercise on activities of daily living and quality of life: a primary care physician's perspective. AB - Evaluation of the environment of patients is an important function of the primary care physician and assists the caregiver in providing an improved quality of life for one's patients. In addition to data collection and therapy, assessment of both the basic and instrumental activities of daily living is a primary concern, especially in patients with chronic diseases such as chronic obstructive pulmonary disease. This article presents the perspective and observation of a primary care physician's management of chronic obstructive pulmonary disease and will give examples of how combined pulmonary rehabilitation and medication improved the quality of life for three patients and show how activities of daily living and quality of life may be seen as a continuum in chronic obstructive pulmonary disease. PMID- 17729078 TI - Return to work in selected disabilities. PMID- 17729079 TI - Partial hand amputation and work. AB - PURPOSE: To determine whether or not subjects who had had a partial hand amputation were able to return to the same job and whether or not they used their silicone finger prosthesis for work. METHOD: Medical records of all the patients who had undergone a traumatic partial hand amputation and who had been treated in the Upper Limb Prosthetic Clinic at the Institute for Rehabilitation in Ljubljana were reviewed. Questionnaires were sent to 112 patients. Forty-eight questionnaires which were returned and had been correctly answered were analysed. RESULTS: The study found that less than half the patients who had had a partial hand amputation were able to do the same work as before the amputation. Less than one-third wore their silicone prosthesis at work regularly. The subjects who did not have manual jobs and who had an amputation of only one or two fingers were able to keep the same job more easily after the amputation. Only a few subjects found their silicone prosthesis useful at work. CONCLUSION: It can be concluded that partial hand amputation may present a great problem in keeping the same job after amputation. An aesthetic (cosmetic) silicone prosthesis is helpful particularly for subjects with higher education whose work involves personal contacts and for whom aesthetics is important. They use the prosthesis for certain activities, such as typing. PMID- 17729080 TI - Return to work after lower limb amputation. AB - PURPOSE: To review the literature on return to work after lower limb amputation. METHOD: A comprehensive review of literature on return to work after lower limb amputation was carried out, searching MEDLINE and PubMED. RESULTS: Most authors found return-to-work rate to be about 66%. Between 22 and 67% of the subjects retained the same occupation, while the remainder had to change occupation. Post amputation jobs were generally more complex with a requirement for a higher level of general educational development and were physically less demanding. The return to work depends on: general factors, such as age, gender and educational level; factors related to impairments and disabilities due to amputation (amputation level, multiple amputations, comorbidity, reason for amputation, persistent stump problems, the time from the injury to obtaining a permanent prosthesis, wearing comfort of the prosthesis, walking distance and restrictions in mobility); and factors related to work and policies (salary, higher job involvement, good support from the implementing body and the employer and social support network). CONCLUSIONS: Subjects have problems returning to work after lower limb amputation. Many have to change their work and/or work only part-time. Vocational rehabilitation and counselling should become a part of rehabilitation programme for all subjects who are of working age after lower limb amputation. Better cooperation between professionals, such as rehabilitation team members, implementing bodies, company doctors and the employers, is necessary. PMID- 17729081 TI - Work in inflammatory and degenerative joint diseases. AB - This article focuses on work disability and sick leave and their cost; it also discusses the value of vocational rehabilitation programmes in rheumatic conditions such as rheumatoid arthritis, ankylosing spondylitis, hip and knee osteoarthritis. It acknowledges the importance of work not only for the worker who has one of these diseases but also for the public purse. Much can be done to improve the health of the persons and reduce their disability and its impact in the workplace which will have an important effect on their and their family's quality of life. It is important that neither rehabilitation nor vocational rehabilitation are regarded as bolt-on activities after drug treatment but are seen as an integral part of effective management. Publications dealing with return to work are relatively common in rheumatoid arthritis, less common in ankylosing spondylitis and relatively rare in osteoarthritis. Vocational rehabilitation programmes should aim to facilitate job retention or, failing that, to improve the ability to return to work. The process must be started with in the health arena and it has to be recognised that slow or poor practice in the health service can jeopardise the patient's work potential. PMID- 17729082 TI - Return to work following spinal cord injury: a review. AB - PURPOSE: To review literature on return to work (RTW) and employment in persons with spinal cord injury (SCI), and present employment rates, factors influencing employment, and interventions aimed at helping people with SCI to obtain and sustain productive work. METHODS: A systematic review for 2000 - 2006 was carried out in PubMed/Medline, AMED, (ISI) Web of Science, EMBASE, CINAHL, PsycInfo and Sociological abstracts database. The keywords 'spinal cord injuries', 'spinal cord disorder', 'spinal cord lesion' or 'spinal cord disease' were cross-indexed with 'employment', 'return to work', 'occupation' or 'vocational'. RESULTS: Out of approximately 270 hits, 110 references were used, plus 13 more found elsewhere. Among individuals with SCI working at the time of injury 21 - 67% returned to work after injury. RTW was higher in persons injured at a younger age, had less severe injuries and higher functional independence. Employment rate improved with time after SCI. Persons with SCI employed ranged from 11.5% to 74%. Individuals who sustained SCI during childhood or adolescence had higher adult employment rates. Most common reported barriers to employment were problems with transportation, health and physical limitations, lack of work experience, education or training, physical or architectural barriers, discrimination by employers, and loss of benefits. Individuals with SCI discontinue working at younger age. CONCLUSIONS: This review confirmed low employment rates after SCI. Future research should explore interventions aimed at helping people with SCI to obtain and sustain productive work. PMID- 17729083 TI - RTW in back conditions. AB - PURPOSE: Back conditions are a group of impairments that induce limitation of activities and restriction of participation, in particular delaying the Return to work (RTW). The purpose of this review is to analyse the components involved in RTW. METHOD: We have included the studies and reviews about the intervention, assessment tools, variables used to forecast the RTW and the cost-benefit ratio. RESULTS: We found a relevant number of studies concerning back conditions and Return to work. The evidence is moderate and the meta-analysis failed to show strong indications of efficacy. The better interventions to facilitate RTW are multidisciplinary, not necessarily intensive but taking into account a bio-psycho social approach. The predictor of RTW does not only concern impairment (pain, rigidity etc.), but the self-estimation of ability is also important to forecast RTW. Intervention seems to be cost-effective if we calculate the saving cost in pension. CONCLUSIONS: Comprehensive bio-psycho-social approaches seem to be the better modality of intervention to facilitate the RTW. More research is needed to obtain more knowledge about these issues. Particular attention should be placed on the choice of outcome measures and the cost-effectiveness of interventions. PMID- 17729084 TI - Return to work following traumatic brain injury: trends and challenges. AB - PURPOSE: The aim of this paper is to present the current knowledge regarding return to work (RTW) following traumatic brain injury (TBI). METHOD: Based on a Medline search, the authors reviewed the current TBI rehabilitation literature regarding (a) predictive factors for successful RTW, and (b) current concepts in rehabilitative strategies for successful RTW. RESULTS: The functional consequences to the victim of traumatic brain injury (TBI) can be severe. Intensive rehabilitative efforts typically emphasize the early phase and address mainly the accompanying functional deficits in the realm of basic activities of daily living and mobility. An otherwise successful medical rehabilitation may end unsuccessfully because of the failure to return to work, with profound consequences to the individual and family, both economic and psychosocial. Even mild TBI may cause lasting problems in tasks calling for sustained attention. There appears to be a complex interaction between pre-morbid characteristics, injury factors, post injury impairments, personal and environmental factors in TBI patients, which influences RTW outcomes in ways that make prediction difficult. Injury severity and lack of self-awareness appear to be the most significant indicators of failure to RTW. Several medical, psychosocial and rehabilitative therapies are currently being implemented in rehabilitation settings which improve the chances of returning to work. CONCLUSION: Accurate prediction of whether a particular TBI patient will successfully return to work is not feasible, with RTW rates in the 12 - 70% range. A significant proportion of TBI patients, including those who are severely injured, are able to return to productive employment if sufficient and appropriate effort is invested. A comprehensive approach - medical and psychosocial - eventually entailing adequate vocational rehabilitation with supported employment can improve outcomes. PMID- 17729085 TI - Return to work in stroke patients. AB - PURPOSE: To present the current state of knowledge regarding return to work (RTW) following stroke. METHOD: A comprehensive review of the current stroke rehabilitation literature pertaining to prognostic and treatment factors for RTW following stroke. RESULTS: Stroke is a major healthcare problem and one of the most expensive diseases in modern society. Stroke results not only in impairment and limitation in basic daily activities; it also impacts on participation in community activities, such as returning to work. Return to work in post-stroke patients has been reported to range between 19% and 73%. Various studies report on return to work in diverse populations, using different follow-up periods, while utilizing variable definitions of stroke and successful work outcomes. The factors positively related to RTW in stroke patients, as found in the literature, are age less then 65 years, high education level and white-collar employment. The significant negative predictor is the severity of stroke. This is indicated by neurological parameters including functional measures of the presence and extent of motor and cognitive impairment. Significantly, the side of the brain damaged and stroke location were not found to be correlated with RTW. Social and financial factors also significantly influence RTW. CONCLUSIONS: RTW in stroke patients should be considered one of the indicators of a successful rehabilitation as it influences self-image, well-being and life satisfaction. There is still a considerable lack of knowledge regarding effective assessments and interventions in vocational rehabilitation in stroke patients. PMID- 17729086 TI - Vocational rehabilitation: a multidisciplinary intervention. AB - Vocational rehabilitation is by definition a multidisciplinary intervention in a process linked to the facilitation of return to work or to the prevention of loss of the work. Clinical staff in contact with a person who has lost his job (general practitioner, specialized physician) must promote vocational rehabilitation. Medical rehabilitation for those with disabilities, whether new or old, has to be followed without delay by vocational rehabilitation. It is even better if these two intertwined processes are overlapping. They involve many professionals including physiotherapists, occupational therapists, psychologists, vocational trainers, job counsellors, teachers, case-managers, job placement agencies. Vocational rehabilitation has a financial cost, borne by many state organizations (security, social system, social affairs) as well as by employers and private insurances, which are in case of accident, concerned by this process. However, the evidence suggests that this is recouped 2- to 10-fold as suggested by the British Society of Rehabilitation Medicine. PMID- 17729087 TI - Medical care services for people with intellectual disabilities living in the general community: a cross-sectional survey of inpatient care utilization in Taiwan, 2001. AB - BACKGROUND: The medical care needs and problems of persons with intellectual disabilities (ID) living in the general community have received limited attention in previous studies. The aim of this article is to describe aspects of medical care utilization among people with ID living in the general community, with particular emphasis on examining the type and determinants of inpatient care utilization in Taiwan. METHODS: A cross-sectional survey of people with intellectual disabilities was employed. A total of 997 respondents who provided fully completed data concerning inpatient care utilization were recruited into the analysis. RESULTS: A total of 12.4% of individuals with intellectual disabilities had used inpatient care in the 7 months prior to the survey. The average number of inpatient care visits in that time was 1.43, with an average hospital stay of 16.91 days. Surgery, fever, gastrointestinal disorders, psychiatric disorders, and accident were the main causes of inpatient care utilization. A stepwise logistic model showed that the factors of holding a Major Illness Card, regular medicine-taking and self-perceived health status were statistically significant to inpatient care utilization of people with intellectual disabilities. CONCLUSIONS: Medical care providers and policy makers need to be aware that many people with intellectual disabilities have increased medical care needs that may require modification of standard medical care practices and service models in society. PMID- 17729088 TI - Perceived participation and problems in participation are determinants of life satisfaction in people with spinal cord injury. AB - PURPOSE: To determine the relationships between perceived participation and problems in participation, and life satisfaction in people with spinal cord injury (SCI). METHOD: A total of 157 men and women with SCI completed the Swedish versions of the Impact on Participation and Autonomy Questionnaire (IPA) and the Life Satisfaction Questionnaire (LiSat-9). RESULTS: The respondents' perceived participation in the five domains of the IPA was significantly correlated with their satisfaction with life as a whole (P < 0.01) and in most of the eight other domains of life satisfaction (P < 0.05 to P < 0.01) in the LiSat-9. The respondents' life satisfaction decreased gradually with increasing frequency of severe problems in participation and significant differences within groups of increasingly severe problems were found. The level of life satisfaction in respondents that perceived no severe problems with participation was similar to those of a normal population. CONCLUSIONS: Perceived participation and problems in participation are determinants of life satisfaction in people with SCI. The results emphasize the importance to focus on severe problems with participation in order to optimize life satisfaction during the rehabilitation after SCI. PMID- 17729089 TI - Personal experience of living with knee osteoarthritis among older adults. AB - PURPOSE: Knee osteoarthritis (OA) is the most common cause of chronic disability amongst community-dwelling older adults. Yet, little is understood about the daily experience of knee OA. As clinicians we fail to understand a large group of individuals that we aim to help. We conducted an exploratory study that aimed to understand the experience of living with knee OA in older adults. METHOD: We used a descriptive phenomenology, grounded in the phenomenology in practice tradition. We conducted nine interviews with participants with physician-diagnosed knee OA, of different ages, sexes, cultural backgrounds and self-perceptions. Ninety minute interviews with each participant were audio-taped and transcribed verbatim. We used the vanKaam method of phenomenological analysis, modified by Moustakas, as the framework for data analysis. FINDINGS: The following five themes on living with knee OA emerged: experiencing knee pain is central to daily living, experiencing mobility limitations devalues self-worth, sharing the experience, assessing our own health and managing chronic pain. CONCLUSIONS: The implications of these findings highlight the profound impact knee OA has on daily living, which have been poorly documented in the past. Clinicians should consider that the consequences of living with knee OA are significant enough to influence a person's sense of self-worth. PMID- 17729090 TI - Management of seating posture of children with cerebral palsy by using thoracic lumbar-sacral orthosis with non-rigid SIDO frame. AB - PURPOSE: To investigate the effects of a special seating device: Thoracic-lumbar sacral orthosis with non-rigid SIDO frame (TLSO-SIDO) in non-ambulant children with cerebral palsy. METHOD: A prospective study with matched pairs (the same subject pre- and post-intervention) was carried out. A comparison of the lateral view of thoracic-lumbar spine X-ray before and after TLSO-SIDO application was made. The assessment of changes in daily activities, posture was recorded by questionnaires. A total of 47 children with cerebral palsy at a mean age of 53.2 months +/- 30.1 SD were involved in the study; 15 (35.71%) of the 42 children showed significant problems in feeding at the beginning of the study period, they were identified as a special subgroup with feeding difficulties. RESULTS: The mean pre-TLSO-SIDO thoracic kyphosis was 53.7 +/- 16.2 in Cobb angle, while the post-TLSO-SIDO thoracic kyphosis was 47.2 +/- 12.1. The lumbar lordosis was 21.3 +/- 13 and in the TLSO-SIDO 17.8 +/- 11.9. The majority of the children have shown improvement in the feeding items and in posture (trunk, head and extremities). The overall satisfaction of the parents with the TLSO-SIDO was very good, namely 3.972 +/- 0.796 on the 5-point analogue scale. We did not find a direct correlation with the improvement in the separate items and the overall satisfaction. CONCLUSION: It is extremely difficult to measure the effect of the postural management on the development of children with cerebral palsy. According to the results of the study, regular application of the TLSO-SIDO in children with spastic cerebral palsy had a beneficial effect on feeding problems and on posture. PMID- 17729091 TI - The hemiplegic arm: interrater reliability and concurrent validity of passive range of motion measurements. AB - PURPOSE: To assess whether our measurement protocol using two raters simultaneously yielded reliable passive range of motion measurements of the hemiplegic arm. Additionally, motion ranges were correlated to several factors to examine the concurrent validity of these measurements. METHOD: Two raters simultaneously assessed five arm motions at baseline, after five and ten weeks in respectively 18, 13 and 12 stroke patients. One tester made the passive movement and the other read the hydrogoniometer. Raters then switched roles. RESULTS: Intraclass correlation coefficients revealed high agreement between the raters with intraclass correlation coefficients (ICCs) ranging between 0.84 and 0.99. Standard errors of measurement and smallest detectable differences were large for shoulder abduction. Significant correlations were found between shoulder external rotation and flexion. All arm motions correlated negatively to pain at the end range of these motions. Shoulder external rotation and flexion were significantly correlated to the time post stroke. Concurrent validity with Ashworth Scale, Fugl Meyer Assessment and Barthel Index was limited. CONCLUSIONS: The current measurement protocol yielded high reliability indices and seems useful for further use. However, standard error of measurement and smallest detectable difference for shoulder abduction were high, implying the necessity to include a large sample size in future studies. Correlations revealed that restricted range of arm motions relate to the time post-stroke and coincide with pain. PMID- 17729092 TI - Oral histories: bridging misconceptions and reality in brain injury recovery. AB - PURPOSE: The purpose of this investigation is to show that listening to oral histories (OH) told by survivors of acquired brain injury (ABI) can influence the attitudes and beliefs held by practicing Speech-Language Pathologists, and graduate and undergraduate students studying communication sciences and disorders. METHOD: Eighty-seven subjects participated in this investigation. Subjects consisted of 27 certified Speech-Language Pathologists (SLPs), 21 graduate students (GS) and 39 undergraduate students (UG) enrolled in a Communication Sciences and Disorders program. Participants responded to a 10-item questionnaire before and after exposure to OH. The questionnaires assessed amount of exposure to adults with ABI, and attitudes and beliefs about the ABI recovery process. RESULTS: Findings indicate that exposure to OH resulted in a significant change in attitudes and beliefs among the participants. UG demonstrated significant changes in all questionnaire items. GS were most influenced on items related to the role of speech therapy in the rehabilitation of speech, language, and cognitive deficits. SLPs were influenced on issues related to social and vocational attainment following ABI. CONCLUSIONS: Oral histories detailing the life-changing effects of ABI and arduous journey to overcome deficits associated with ABI may have an impact in better understanding these issues. PMID- 17729093 TI - The stigmatisation of people with chronic back pain. AB - PURPOSE: This study responded to the need for better theoretical understanding of experiences that shape the beliefs, attitudes and needs of chronic back patients attending pain clinics. The aim was explore and conceptualise the experiences of people of working age who seek help from pain clinics for chronic back pain. METHODS: This was a qualitative study, based on an interpretative phenomenological approach (IPA). During in-depth interviews in their homes, participants were invited to 'tell their story' from the time their pain began. Participants were twelve male and six female patients, aged between 28 and 62 years, diagnosed as having chronic benign back pain. All had recently attended one of two pain clinics as new referrals. The interview transcripts were analysed thematically. FINDINGS: Stigmatisation emerged as a key theme from the narrative accounts of participants. The findings expose subtle as well as overt stigmatising responses by family, friends, health professionals and the general public which appeared to have a profound effect on the perceptions, self esteem and behaviours of those interviewed. CONCLUSIONS: The findings suggest that patients with chronic back pain feel stigmatised by the time they attend pain clinics and this may affect their attitudes and behaviours towards those offering professional help. Theories of chronic pain need to accommodate these responses, while pain management programmes need to address the realities and practicalities of dealing with stigma in everyday life. PMID- 17729094 TI - The treatment of phantom limb pain using immersive virtual reality: three case studies. AB - PURPOSE: This paper describes the design and implementation of a case study based investigation using immersive virtual reality as a treatment for phantom limb pain. METHOD: Three participants who experienced phantom limb pain (two with an upper-limb amputation, and one with a lower-limb amputation) took part in between 2 and 5 immersive virtual reality (IVR) sessions over a 3-week period. The movements of participants' anatomical limbs were transposed into the movements of a virtual limb, presented in the phenomenal space of their phantom limb. RESULTS: Preliminary qualitative findings are reported here to assess proof of principle for this IVR equipment. All participants reported the transferal of sensations into the muscles and joints of the phantom limb, and all participants reported a decrease in phantom pain during at least one of the sessions. CONCLUSION: The authors suggest the need for further research using control trials. PMID- 17729095 TI - Rheumatoid arthritis in Lithuania: need for external help from the onset of disease. AB - PURPOSE: To estimate the burden of rheumatoid arthritis (RA) in Vilnius, Lithuania, the former socialist country in Eastern Europe, in terms of patients' need for help from other persons and to explore the factors which influence the need for physical help. METHOD: Some 537 patients with RA, registered in Vilnius, answered questions about socio-demographics, disease characteristics, categories of required help, the use of major appliances and adaptations, underwent a clinical examination and filled in the modified health assessment questionnaire (MHAQ) and arthritis impact measurement scale (AIMS). Logistic regression was used to assess which variables from those explored influenced the need for physical help. RESULTS: A total of 230 (42.9%) patients out of 537 were requiring help from other persons, and the proportion was equally high in all the disease duration categories. A quarter of the patients (25.1%) were classified to ACR III and IV functional impairment groups. In multivariate logistic regression model the risk to become dependent on external help ultimately depended on MHAQ (10.32 [CI 95% 6.57; 16.23], p < 0.001) but the use of joint stabilization measures (1.97 [CI 95% 1.06; 3.64], p < 0.01) and 28 tender joints count (1.02 [CI 95% 1.0; 1.06], p < 0.05) were also important. CONCLUSIONS: Nearly half of the patients reported being dependent on others and a quarter of patients were in definite need for that. The functional impairment is the most important risk factor, although identifying the group using joint stabilization measures routinely may be of practical value in order to define the risk group which may need the external help in future. PMID- 17729096 TI - Two steps forward, one step back? A commentary on the disease-specific core sets of the International Classification of Functioning, Disability and Health (ICF). AB - PURPOSE: The International Classification of Functioning, Disability and Health (ICF) has been received favourably by health care professionals, disability rights organizations and proponents of the social model of disability. The success of the ICF largely depends on its uptake in practice and is considered unwieldy in its full format. To enhance the application of the ICF in practice, disease and site-specific core sets have been developed. The objective of this paper is to stimulate thought and discussion about the place of the ICF core sets in rehabilitation practice. METHOD: The authors' review of the literature uses the ICF core sets (especially stroke), to debate if the ICF is at risk of taking two steps forward, one step back in its holistic portrayal of health. CONCLUSION: ICF disease specific core sets could be seen as taking two steps forward to enhance the user friendliness of the ICF and evidence-based practice in rehabilitation. However, there is a danger of taking one step back in reverting to a disease-specific classification. It is too early to conclude the efficacy of the disease-specific core sets, but there is an opportunity to debate where the next steps may lead. PMID- 17729097 TI - Corneal critical barrier against the penetration of dexamethasone and lomefloxacin hydrochloride: evaluation by the activation energy for drug partition and diffusion in cornea. AB - The cornea is a solid barrier against drug permeation. We searched the critical barrier of corneal drug permeation using a hydrophobic drug, dexamethasone (DM), and a hydrophilic drug, lomefloxacin hydrochloride (LFLX). The activation energies for permeability of DM and LFLX across the intact cornea were 88.0 and 42.1 kJ/mol, respectively. Their activation energies for permeability across the cornea without epithelium decreased to 33.1 and 16.6 kJ/mol, respectively. The results show that epithelium is the critical barrier on the cornea against the permeation of a hydrophobic drug of DM as well as a hydrophilic drug of LFLX. The activation energy of partition for DM (66.8 kJ/mol) was approximately 3-fold larger than that of diffusion (21.2 kJ/mol). The results indicate that the partition for the hydrophobic drug of DM to the corneal epithelium is the primary barrier. Thermodynamic evaluation of activation energy for the drug permeation parameters is a good approach to investigate the mechanism of drug permeability. PMID- 17729098 TI - Solid carriers for improved solubility of glipizide in osmotically controlled oral drug delivery system. AB - The purpose of this study was to increase the solubility of glipizide (gli) by solid dispersions SDs technique with polyvinylpyrrolidone (PVP) in aqueous media. The gli-PVP solid dispersion systems was prepared by physical mixing or spray drying method, and characterized by differential scanning calorimetry (DSC), X ray powder diffraction (XRD) analysis, Fourier transformation-infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The elementary osmotic pumps (EOPs) were prepared with gli-PVP complex and the effect of the PVP percentages on the enhancing of gli dissolution rate was studied. The influences of various parameters e.g., drug- PVP ratio, level of solubility modifier, coating weight gain and diameter of drug releasing orifice on drug release profiles were also investigated. The solubility and dissolution rates of gli were significantly increased by solid dispersion using spray dried method as well as their physical mixture. The obtained results indicated that gli-PVP solid dispersion system has suitable solubility behavior in EOP tablets. PMID- 17729099 TI - Pharmacokinetics of doxazosin gastrointestinal therapeutic system after multiple administration in Korean healthy volunteers. AB - Doxazosin mesylate is a selective alpha-adrenoreceptor antagonist for the treatment of hypertension and benign prostatic hyperplasia. A simple high performance liquid chromatographic method has been developed and validated for the quantitative determination of doxazosin in plasma. A reversed phase C18 column was used for the separation of doxazosin and prazosin (internal standard) with a mobile phase composed of water, acetonitrile, triethylamine (68:32:0.2 v/v, pH 5.0) at a flow rate of 1.2 mL/min. The fluorescence detector was operated at 246 (excitation) and 389 nm (emission). Intra- and inter-day precision and accuracy were acceptable for all quality control samples including the lower limit of quantification of 1 ng/mL. Recovery of doxazosin from human plasma was greater than 93.4%. Doxazosin was stable in human plasma under various storage conditions. This method was used successfully for a pharmacokinetic study in plasma after oral administration of multiple 4-mg dose of doxazosin gastrointestinal therapeutic system formulation to 16 healthy volunteers. At steady state the mean area under the curve for a dosing interval and elimination half-life were calculated to be 367.0 +/- 63.5 ng x hr/mL and 29.2 +/- 4.5 hr, respectively. There was no difference in pharmacokinetic parameters between male and female. PMID- 17729100 TI - Quantitative determination of acetaminophen in pharmaceutical formulations using differential scanning calorimetry. Comparison with spectrophotometric method. AB - In this paper our previous researches dealing with compatibility, thermoanalytical characterization, the kinetics of thermal degradation of acetaminophen, either pure or contained in some commercial pharmaceutical formulations, have found applications outlets. In a previous investigation the possible interactions between acetaminophen and four excipients contained in the commercial pharmaceutical formulations were tested. As a continuation of this research in the present study an analytical method based on differential scanning calorimetry (DSC) was applied to determine the acetaminophen content of four commercial pharmaceutical formulations. For a fifth drug it was shown that the method is not applicable owing to observed incompatibility with one of the excipients. Finally, the analytical results obtained were compared with those derived from two UV spectrophotometric methods (one, i.e., "direct method," recommended by the Pharmacopeia and the other based on the first-order derivative UV spectra). PMID- 17729101 TI - Characterization of antioxidant activity of extracts from Flos Lonicerae. AB - Antioxidants are emerging as prophylactic and therapeutic agents for various diseases. However, little is known about the antioxidant property of the extract from Flos Lonicerae, a medically useful traditional Chinese medicine herb. Here the antioxidant capacity of water, methanolic and 70% ethanolic extracts prepared from Flos Lonicerae to scavenge DPPH radical and reduce Fe(3+) to Fe(2+) is evaluated. Chlorogenic acid, a major component of Flos Lonicerae, is identified and further purified from 70% ethanolic extract with HPLC and its antioxidant capacity is also characterized. The content of total phenolic compounds and chlorogenic acid in Flos Lonicerae is determined. The present results demonstrate that all Flos Lonicerae extracts examined here exhibit antioxidant activity and chlorogenic acid is a major contributor to this activity, which implicates that the Flos Lonicerae extract may serve as potential source of natural antioxidants for treatment of some diseases. PMID- 17729102 TI - Eudragit coating of chitosan-prednisolone conjugate microspheres and in vitro evaluation of coated microspheres. AB - Chitosan-prednisolone conjugate microspheres (Ch-SP-MS) were prepared, and Eudragit coating was applied in order to efficiently deliver the microspheres and drug to the intestinal disease sites. The Eudragit L100-coated microspheres (Ch SP-MS/EuL100) were examined for particle characteristics and the release of drug and Ch-SP-MS in different pH media at 37 degrees C. Ch-SP-MS were spherical, with a mean size of 4.5 microm and prednisolone content of 3.3% (w/w). Ch-SP-MS/EuL100 were fairly spherical, with a mean size of 22. 5 microm and drug content of 0.32% (w/w). At pH 1.2, the release extent was less than 5% even at 48 h, and Eudragit coating tended to suppress the release. In contrast, at pH 6.8 and 7.4, Ch-SP MS/EuL100 tended to show somewhat faster drug release than Ch-SP-MS. Ch-SP MS/EuL100 displayed a release extent of 23 and 27% at pH 6.8 and 7.4, respectively. Ch-SP-MS aggregated at pH 1.2, but almost kept their initial size and shape at pH 6.8 and 7.4. Ch-SP-MS/EuL100 almost maintained their original shape and size at pH 1.2, and gradually released Ch-SP-MS at pH 6.8 and 7.4 due to dissolution of the Eudragit layer. Eudragit coating is suggested to be useful to efficiently deliver Ch-SP-MS to the intestinal disease sites. PMID- 17729103 TI - Mucoadhesive dosage form of lidocaine hydrochloride: I. Mucoadhesive and physicochemical characterization. AB - The aim of this study was to characterize a buccal mucoadhesive film using lidocaine and its hydrochloride salt (LDHCL) as a model drug. Buccal films were developed using carbopol 971P as a mucoadhesive polymer, and glycerol as a plasticizer. Scanning Electron Microscope, Differential Scanning Calorimetry, X ray powder diffraction, and Fourier Transform Infra Red techniques were used to characterize the mucoadhesive films. Bioadhesive properties were evaluated using the Universal Instron Instrument with chicken pouch as a model tissue. LDHCL and its base were present in carbopol 971P films in a molecular dispersion state without exerting any effect on the glass transition of these films. The mucoadhesive force between the chicken pouches and the film containing glycerol did not change by time during the tested period (1-20 min), while increased with increasing the amount of glycerol (10-40% w/w of polymer content). Furthermore, a linear increase in the mucoadhesive force was accompanied by the increase in the film thickness, while a linear decrease followed by plateau was obtained when loading the patch with LDHCL at concentration above 1 mg/cm(2). Loading carbopol film with lidocaine base, in a concentration up to 6 mg/cm(2) decreased linearly the mucoadhesive properties, which could be attributed to salt formation between the acidic carboxylic moiety of carbopol and basic lidocaine. PMID- 17729104 TI - Current perspectives of solubilization: potential for improved bioavailability. AB - This review focuses on the recent techniques of solubilization for the attainment of effective absorption and improved bioavailability. Solubilization may be affected due to cosolvent water interaction or altered crystal structure by cosolvent addition. Micellar solubilization could be affected by both ionic strength and pH. Addition of cosolvents to the surfactant solutions offers only a small advantage because of the decrease in the solubilization capacity of the micelles. Polymorphism is known to influence dissolution and bioavailability of the drugs. Molecular modeling study of cyclodextrin inclusion complexations can predict the inclusion modes, stoichiometry of the complex, and the relative complexing efficiency of cyclodextrins with various drug molecules. PMID- 17729106 TI - Synthesis of chemically cross-linked hydroxypropyl methyl cellulose hydrogels and their application in controlled release of 5-amino salicylic acid. AB - The objective of this study was to achieve the colon-specific delivery of an anti ulcerative colitis drug using hydroxypropyl methyl cellulose (HPMC) hydrogels. HPMC hydrogels containing poly ethylene glycol (PEG) as cross-links have been prepared by reacting HPMC sodium salt with polyethylene glycol dichloride. The effect of cross-linking agent on swelling behavior of HPMC-PEG hydrogels, were investigated. Swelling parameters such as equilibrium degree of swelling, swelling ratio and network parameter such as molecular mass between cross-links (M(c)) were determined. The cross-linking concentrations were 0.5%, 1%, 1.5%, and 2% (based on weight of HPMC). The equilibrium swelling ratio (Q) of cross-linked HPMC hydrogels increases from 13.2 to 27.1 as the cross-linker percentage increases from 0.5% to 2%. 5-Aminosalicylic acid (5-ASA) was used as a model of an anti-inflammatory drug. Cross-linked HPMC hydrogels were found to be a promising drug delivery system for the drugs to be delivered to the colon. PMID- 17729105 TI - Enhancement of the skin permeation of clindamycin phosphate by Aerosol OT/1 butanol microemulsions. AB - Microemulsions of water/isopropyl palmitate (IPP)/Aerosol OT (AOT)/1-butanol were developed as alternative formulations for topical delivery of clindamycin phosphate. Effect of AOT:1-butanol ratios on microemulsion region existence in the pseudoternary phase diagrams was investigated. The 2:1 AOT:1-butanol provided the largest microemulsion region. Five microemulsions of 1% w/w clindamycin phosphate were prepared and characterized. The permeation through human epidermis of the microemulsions was evaluated and compared with the 70% isopropanol solution using modified Franz diffusion cells. The drug permeation from all microemulsions was found to be significantly greater than that from the solution, indicating the enhancement of the skin permeation by the microemulsions. Within the same microemulsion type, the drug permeation increased with increasing the amount of AOT:1-butanol. The drug permeation from oil-in-water (o/w) microemulsions was relatively higher than that from water-in-oil (w/o) microemulsions. In addition, all microemulsions were stable for at least three months at 30 +/- 1 degrees C. PMID- 17729107 TI - Preparation and characterization of solid dispersions of dipyridamole with a carrier "copolyvidonum Plasdone S-630". AB - Solid dispersions (SDs) of dipyridamole (DIP) with a novel carrier copolyvidonum Plasdone S-630 (CoPVP) were developed by solvent evaporation method. The solid state of SDs of DIP with CoPVP (SDs CoPVP) was characterized by fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and polarizing microscopy, compared with that of SDs of DIP with polyvinylpyrrolidone Plasdone K-29/32 (SDs PVP). FT-IR analysis demonstrated the presence of intermolecular hydrogen bonding between DIP and CoPVP or PVP in SDs. DSC and XRD studies indicated that DIP presented in amorphous state in both SDs CoPVP and SDs PVP at higher weight ratios. The dissolution property of SDs CoPVP was significantly improved in comparison of pure DIP and physical mixtures with CoPVP (PM CoPVP). Both SDs CoPVP and SDs PVP powder showed the favorable flowability. However, SDs CoPVP showed better compressibility than SDs PVP. The lower hydroscopicity of SDs CoPVP could be advantageous to the stability to SDs. This study proves the potential of CoPVP as a carrier in the formulations of SDs for poorly soluble drugs. PMID- 17729108 TI - Phase characterization of indomethacin in adsorbates onto hydroxyethylcellulose. AB - The phase state and solubility of indomethacin in adsorbates onto hydroxyethylcellulose have been studied. The characterization of the adsorbates and their relevant physical mixtures was made by the use of DSC, X-ray diffractometry, FT-IR spectrometry, and solubility analysis. The drug-to-polymer ratio determines either a partial crystallization of the metastable alpha-form onto hydroxyethylcellulose surface or complete inhibition of indomethacin crystallization. Significantly improved drug aqueous solubility was achieved. A stable immobilization of indomethacin molecules onto hydroxyethylcellulose due to drug/polymer interactions can be assumed. The changed indomethacin phase state in the adsorbates remains stable for one-year storage at ambient conditions. These results could be of practical importance. PMID- 17729110 TI - Oxidants and antioxidants revisited. New concepts of oxidative stress. PMID- 17729111 TI - Catalase deficiency may complicate urate oxidase (rasburicase) therapy. AB - Patients with low (inherited and acquired) catalase activities who are treated with infusion of uric acid oxidase because they are at risk of tumour lysis syndrome may experience very high concentrations of hydrogen peroxide. They may suffer from methemoglobinaemia and haemolytic anaemia which may be attributed either to deficiency of glucose-6-phosphate dehydrogenase or to other unknown circumstances. Data have not been reported from catalase deficient patients who were treated with uric acid oxidase. It may be hypothesized that their decreased blood catalase could lead to the increased concentration of hydrogen peroxide which may cause haemolysis and formation of methemoglobin. Blood catalase activity should be measured for patients at risk of tumour lysis syndrome prior to uric acid oxidase treatment. PMID- 17729113 TI - The endogenous reactive oxygen species promote NF-kappaB activation by targeting on activation of NF-kappaB-inducing kinase in oral squamous carcinoma cells. AB - Reactive oxygen species (ROS) could stimulate or inhibit NF-kappaB pathways. However, most results have been obtained on the basis of the exogenous ROS and the molecular target of ROS in NF-kappaB signalling pathways has remained unclear. Here, the oral squamous carcinoma (OSC) cells, with a mild difference in the endogenous ROS level, were used to investigate how slight fluctuation of the endogenous ROS regulates NF-kappaB activation. This study demonstrates that NF kappaB-inducing kinase (NIK) is a critical target of the endogenous ROS in NF kappaB pathways. The results indicate that ROS may function as a physiological signalling modulator on NF-kappaB signalling cascades through its ability to facilitate the activity of NIK and subsequent NF-kappaB transactivation. In addition, the data are useful to explain why the altered intracellular microenvironment related to redox state may influence biological behaviours of cancer cells. PMID- 17729112 TI - Changes in urinary dinor dihydro F(2)-isoprostane metabolite concentrations, a marker of oxidative stress, during and following asthma exacerbations. AB - To investigate changes in oxidant stress during and following acute asthma exacerbations, this study measured 2,3-dinor-5,6-dihydro-15-F(2t)-IsoP (F(2)-IsoP M), the major urinary metabolite of 15-F(2t)-IsoP, in eight asthmatic adults, during and following an asthma hospitalization. F(2)-IsoP-M concentrations at admission and follow-up were significantly higher than discharge (admission median: 4.12 ng/Cr mg, range 1.89-7.8; follow-up: 2.47 ng/Cr mg (1.56-6.86); discharge: 1.42 ng/Cr mg (0.7-4.44); both p<0.01), but not significantly different between admission and follow-up. F(2)-IsoP-M concentrations at follow up were higher than a control group with stable asthma (0.68 ng/Cr mg (0.31-1.5), p=0.0008). In conclusion, asthma exacerbations requiring hospitalization are associated with 6-fold higher urinary F(2)-IsoP-M concentrations compared to stable asthmatics. F(2)-IsoP-M concentrations decreased significantly during hospitalization, but significant elevations 3 months following hospitalization suggest ongoing oxidative stress despite clinical improvement. Urinary F(2)-IsoP M may be a clinically useful, simple non-invasive systemic measure of oxidative stress in asthmatics, providing information not captured by spirometry or symptoms. PMID- 17729114 TI - Modulation of Fas-FasL related apoptosis by PBN in the early phases of choline deficient diet-mediated hepatocarcinogenesis in rats. AB - This study focused on the detection of apoptosis related events in very early phases of choline-deficient (CD)-induced hepatocarcinogenesis (at 2-5 weeks). Flow cytometry of isolated intact primary hepatocytes from CD diet fed rats indicated increased expression of the apoptosis-associated protein Fas. Increased apoptosis in CD-treated livers was confirmed by Western blot analyses of caspases and cytochrome c. This study was also able to detect differences in apoptotic events following phenyl butyl nitrone (PBN) treatment. Fas expression was inhibited by PBN, indicating that PBN is anti-apoptotic. It is speculated that in the early stages of CD-induced hepatotoxicity, PBN is involved in inhibiting pro inflammatory factor-driven apoptosis of normal hepatocytes, which protects against the initiation of carcinogenesis. The CD diet model is also considered as a model for non-alcoholic steatohepatitis (NASH) in humans and early expression of Fas could also be a good index of the progression of NASH. PMID- 17729115 TI - Insinuation of exacerbated oxidative stress in sucrose-fed rats with a low dietary intake of magnesium: evidence of oxidative damage to proteins. AB - High sucrose diets and low magnesium intake have been independently implicated in induction of oxidative stress in animal models. The aim of this study was to investigate whether low dietary magnesium intake exacerbates the prooxidant effects of high sucrose feeding. Rats were fed control (C), high sucrose (HS); low magnesium (LM) and high sucrose low magnesium (HSLM) diets for 90 days and oxidative stress evaluated in terms of formation of TBARS, advanced oxidation protein products and protein carbonyls. HS and LM rats showed evidence of lipid peroxidation and protein oxidation in plasma and liver. Enhanced oxidative injury to lipids and proteins after HSLM feeding was indicated by increased carbonyl content (p <0.01) and significantly (p <0.005) higher levels of TBARS in plasma and hepatic tissue relative to both HS and LM groups. Altogether, these results illustrate the potential detrimental and cumulative effects of low magnesium intake combined with high sucrose consumption on oxidative stress variables. PMID- 17729116 TI - Hemin-induced Erk1/2 activation and heme oxygenase-1 expression in human umbilical vein endothelial cells. AB - Hemin has been reported to be protective in the pathological process, but its protective mechanisms have not been precisely defined. Hemin could induce Erk1/2 phosphorylation in astrocyte. Erk1/2 phosphorylation has been proved to be involved in many growth signals cellular transduction. However, little study has been conducted as to the relationship between hemin and Erk1/2 activation in human umbilical vein endothelial cells (HUVECs). The present study aimed to investigate the relationship between hemin and Erk1/2 phosphorylation in HUVECs. The results showed that low concentration of hemin induced and sustained phosphorylation of Erk1/2 for a long time. The HO inhibitor protoporphyrin IX zinc (II) abrogated phosphorylation of Erk1/2 induced by hemin. Biliverdin, one of the metabolites of hemin, obviously induced the Erk1/2 phosphorylation in HUVECs. Both hemin and biliverdin promoted HUVEC cell growth. The results strongly suggested that hemin could induce and sustain Erk1/2 phosphorylation in HUVECs by way of HO-1 induction and biliverdin produced from HO-1 catalysing hemin degradation. PMID- 17729117 TI - Urinary excretion rates of 8-oxoGua and 8-oxodG and antioxidant vitamins level as a measure of oxidative status in healthy, full-term newborns. AB - The aim of the present study was to evaluate the oxidative status in healthy full term children and piglets. Urinary excretion of 8-oxoGua (8-oxoguanine) and 8 oxodG (8-oxo-2'-deoxyguanosine) were determined using HPLC/GS/MS methodology and concentrations of vitamins A, C and E with HPLC technique. The levels of 8-oxoGua in urine samples were about 7-8 times higher in newborn children and piglets when compared with the level of adult subjects, while in the case of 8-oxodG the difference was about 2.5 times. The levels of vitamin C and E in umbilical cord blood of newborn children significantly depend on the concentration of these compounds in their mother's blood. However, the values of vitamin C in human's cord blood were about 2-times higher than in respective mother blood, while the level of vitamin E showed an opposite trend. The results suggest that: (i) healthy, full-term newborns are under potential oxidative stress; (ii) urinary excretion of 8-oxoGua and 8-oxodG may be a good marker of oxidative stress in newborns; and (iii) antioxidant vitamins, especially vitamin C, play an important role in protecting newborns against oxidative stress. PMID- 17729118 TI - Bicarbonate and active site zinc modulate the self-peroxidation of bovine copper zinc superoxide dismutase. AB - Peroxidation reactions of copper-zinc superoxide dismutase (CuZn-SOD1) or its zinc-depleted form (CuE-SOD1) that likely also involve a component of bicarbonate buffer have been implicated in the pathophysiology of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS), Alzheimer's Disease and Parkinson's Disease. Neither removal of the zinc ion nor adding bicarbonate had large effects on the self-peroxidation reaction of bovine SOD1, but the combination of zinc deficiency and added bicarbonate caused major changes to the spin trapped SOD1 centred free radical. Removal of the active site zinc ion greatly decreased the formation of an unassigned SOD1-centred free radical in the reaction with the inorganic peroxide peroxynitrite. The results suggest that under cellular conditions ( approximately 5 mM bicarbonate) zinc-deficient SOD1 peroxidation could play a pathogenic role in neurodegenerative diseases. PMID- 17729119 TI - UVB irradiation-induced impairment of keratinocytes and adaptive responses to oxidative stress. AB - UVB irradiation of human skin is known to induce pathophysiological processes as oxidative stress and inflammation. HaCaT keratinocytes represent a well established in vitro model system to investigate the influence of UVB irradiation on cell cultures. It was the aim of these investigations to study the effects of moderate UVB doses on cellular and mitochondrial integrity of HaCaT keratinocytes, biomarkers of oxidative stress and antioxidant protection by superoxide dismutases. F(2)-isoprostane concentrations were UVB dose-dependently enhanced reaching a plateau at 50 mJ/cm(2). Cell viability was reduced and apoptosis was enhanced with increasing UVB doses. The activities of the respiratory chain complexes were practically not altered at lower UVB doses, up to 50 mJ/cm(2), whereas remarkable decreases, also for the levels of cardiolipin species, were seen at 100 mJ/cm(2). As an adaptive response to the enhanced oxidative stress, protein levels of MnSOD increased about 3-fold at 50 mJ/cm(2) and decreased at higher doses. From the data it can be concluded that keratinocytes are sufficiently protected at low UVB doses, whereas higher doses lead to irreversible cell damage. PMID- 17729121 TI - Fluidity and oxidative stress in erythrocytes from very low birth weight infants during their first 7 days of life. AB - OBJECTIVE: To study the evolution of lipid peroxidation, enzymatic antioxidants response, lipid profile and membrane fluidity in erythrocytes from very low birth weight (VLBW) infants during their first 7 days of extra-uterine life. STUDY DESIGN: One hundred and twenty infants were selected and divided in two groups according to their weight and gestational age. Hydroperoxides, fatty-acid profile, fluidity (DPH and TMA-DPH) and catalase, SOD and GPx activities were measured in erythrocytes. RESULTS: VLBW group showed higher concentration of hydroperoxides and lower membrane fluidity during the first 72 h, lower SOD activity during the first 3 h and higher GPx activity during the first 7 days of life. Also, this group showed lower n-3 polyunsaturated fatty-acids percentage with respect to the term group. CONCLUSION: Erythrocytes from VLBW infants showed higher oxidative damage and lower fluidity in their membranes, at least during the first 3 days of extra-uterine life, which may cause alterations in their functions and flexibility. PMID- 17729120 TI - Simvastatin enhances induction of inducible nitric oxide synthase in 3T3-L1 adipocytes. AB - The present study was designed to determine whether hydroxymethylglutaryl-CoA reductase inhibitors (statins) modulate the NO production via iNOS in adipocytes stimulated by lipopolysaccharide (L) and tumour necrosis factor-alpha (T). Well differentiated 3T3-L1 adipocytes significantly produced NO by LT-treatment. Pre incubation with simvastatin, a lipophilic statin, pravastatin, a hydrophilic one, or Y27632, an inhibitor of Rho kinase, further enhanced the production of NO. The effect of simvastatin was offset by mevalonate and geranylgeranyl pyrophosphate (GGPP) but not by squalene. The mRNA level for iNOS parallelled the NO production. The NF-kappaB was activated by the LT-treatment and was further enhanced by simvastatin, pravastatin or Y27632 addition. Mevalonate and GGPP completely offset the effect of simvastatin. Statins and Y27632 also further increased the interleukin-6 secretion in the LT-treated 3T3-L1 adipocytes. These results suggest that statins, especially lipophilic type, enhance induction of iNOS by inhibiting the small GTP-binding protein signal in adipocytes. PMID- 17729122 TI - Mitochondria-targeted antioxidants do not prevent tumour necrosis factor-induced necrosis of L929 cells. AB - Mitochondrial production of reactive oxygen species (ROS) is widely reported as a central effector during TNF-induced necrosis. The effect of a family of mitochondria-targeted antioxidants on TNF-induced necrosis of L929 cells was studied. While the commonly used lipid-soluble antioxidant BHA effectively protected cells from TNF-induced necrosis, the mitochondria-targeted antioxidants MitoQ(3), MitoQ(5), MitoQ(10) and MitoPBN had no effect on TNF-induced necrosis. Since BHA also acts as an uncoupler of mitochondrial membrane potential, two additional uncouplers were tested. FCCP and CCCP both provided dose-dependent inhibition of TNF-induced necrosis. In conclusion, the generation of mitochondrial ROS may not be necessary for TNF-induced necrosis. Instead, these results suggest alternative mitochondrial functions, such as a respiration dependent process, are critical for necrotic death. PMID- 17729124 TI - Spin-labelled lutein as a new antioxidant in protection against lipid peroxidation. AB - A new potentially antioxidant compound, spin-labelled lutein (SL-lut), was synthesized and incorporated into egg yolk phosphatidylcholine (EYPC) liposome membrane. The approximate location of nitroxide free radical groups of SL-lut was determined based on electron paramagnetic resonance (EPR) spectra. Then the ability of SL-lut to protect EYPC liposomes against lipid peroxidation (LPO) was compared to the antioxidant effects of lutein and a nitroxide spin label 3 carbamoyl-2,2,5,5-tetramethylpyrrolidin-1-yloxy (3-CP). Two free radical generation systems were used - a thermal decomposition of 2,2'-azobis (2,4 dimethyl-valeronitrile) (AMVN) and a modified Fenton reaction using ferric-8 hydroxyquinoline (Fe(HQ)(3)). Determination of the amount of thiobarbituric acid reactive species (TBARS) was used as a measure of LPO. SL-lut was the most powerful antioxidant, reducing LPO by about 6-times in AMVN-treated liposomes and 7-times in Fe(HQ)(3)-treated liposomes. Lutein alone gave only a moderate protection in both systems, while 3-CP was as efficient as SL-lut in the presence of AMVN, but not efficient whatsoever in the presence of Fe(HQ)(3). The results suggest that a nitroxide part of SL-lut plays an important role in enhancing the antioxidant activity of lutein and makes SL-lut a powerful antioxidant efficient under different conditions. PMID- 17729123 TI - Investigating the free radical trapping ability of NXY-059, S-PBN and PBN. AB - The spin trapping ability of the nitrones 2,4-disulphophenyl-N-tert-butyl nitrone (NXY-059), 2-sulphophenyl-N-tert-butyl nitrone (S-PBN) and alpha-phenyl-N-tert butyl nitrone (PBN) for both hydroxyl and methanol radicals was investigated using electron paramagnetic resonance (EPR) spectroscopy. The radicals of interest were generated in situ in the spectrometer under constant flow conditions in the presence of each nitrone. The spin adducts formed were detected by EPR spectroscopy. This approach allowed for quantitative comparison of the EPR spectra of the spin adducts of each nitrone. The results obtained showed that NXY 059 trapped a greater number of hydroxyl and methanol radicals than the other two nitrones, under the conditions studied. PMID- 17729125 TI - Changes in alpha-tocopherol and retinol levels during cardiopulmonary bypass correlate with maximal arterial partial pressure of oxygen. AB - Cardiopulmonary bypass (CPB) is associated with oxidative stress. This study examined antioxidant levels in adults undergoing CPB surgery and their correlation with clinical variables. Arterial blood samples were obtained from 27 patients undergoing CPB. The time-course variation of vitamin C (spectrofluorimetry), alpha-tocopherol and retinol (HPLC) levels were determined. Plasma vitamin C rose initially but gradually decayed during reperfusion until 60% reduction of baseline values post-surgery. alpha-Tocopherol and retinol were reduced along CPB with post-operative values approximately 25% lower than baseline. No significant changes were found for selenium and glutathione peroxidase. PaO(2) values rose steadily throughout CPB. A correlation existed for alpha-tocopherol and retinol depletion vs maximal PaO(2) throughout CPB but no correlation was found for antioxidant consumption vs duration of ischaemia and reperfusion and hypothermia level. In conclusion, consumption of arterial blood antioxidant vitamins occurs with CPB in relation with PaO(2) levels but not for other clinical variables measured in this study. PMID- 17729127 TI - Women and HIV/AIDS in China: gender and vulnerability. AB - A comprehensive literature review was conducted to determine if there was a research gap between women's vulnerability to HIV and research addressing that vulnerability in China. Turmen's article Gender and HIV/AIDS served as a framework for examining the eight determinants placing women and adolescent girls at greater risk of HIV infection than men. Eighty-eight research reports were retrieved and categorized by general characteristics and the eight determinants. Women were found to be more vulnerable than men to HIV infection in China and worldwide. While researchers reported a considerable amount of research regarding women's HIV/AIDS-related issues in China, there is insufficient attention to some risk determinants. Investigators are encouraged to take advantage of political commitment and policy changes in China to conduct more research focusing on female vulnerability and to address the effects of violence, laws, stigma, and discrimination in female HIV prevention. PMID- 17729128 TI - Women's choice of strategies for improving utilization of HIV/AIDS screening services. AB - Our purpose in the study was to examine women's choice of strategies for improving utilization of HIV/AIDS screening. A-26-item questionnaire was used to gather data from a purposive sample of 1,052 women seeking care in three government hospitals in Akwa Ibom State, Nigeria. Findings revealed that the strategies mostly accepted in order included the following: providing awareness on screening services; routine health education on screening services in health facilities and community; and integrating screening advocacy in all educational curricula. Chi-square analysis revealed that age and marital status significantly influenced women's choice of the strategies. The strategies were recommended for adoption in HIV/AIDS prevention programs in the state. PMID- 17729129 TI - The impact of migration on HIV prevention for women: constructing a conceptual framework. AB - There are an estimated 40.5 million people currently living with HIV globally, 17.5 million of whom are women, according to the AIDS Epidemic update: December 2005, conducted by UNAIDS and the World Health Organization (WHO) 2005. Women are vulnerable to HIV for biologic as well as social reasons. In the past, the HIV prevention theorists have not considered the context of women's lives: factors at the individual, relationship, and community levels, as well as structural factors (both policy and cultural) impact on HIV prevention for women. This is particularly true for migrant women, who may be especially vulnerable to HIV infection during their time of transition. Throughout this article I explore the international literature for both the historical context of HIV prevention for women and the impact of migration on HIV risk for women. The literature review provides a basis for the development of a conceptual framework of the socioecologic factors affecting HIV prevention for migrant women. I call for consideration of the broad context of women's experience when developing interventions for this population. PMID- 17729130 TI - The lived experiences of HIV-positive, pregnant women in Thailand. AB - The purpose of our study was to examine the lived experiences of 10 pregnant women in Thailand following their HIV diagnosis. Principles of interpretive phenomenology were applied to guide the study. In-depth interviews with open ended questions were conducted during 2000-2001. Each participant met with the research team from 5 to 12 times. "Struggle" was the main theme that emerged from participants' lived experiences, with four subthemes: struggling alone, sharing one's struggling, struggling for the baby, and struggling through ups and downs. Findings from our study resulted in helpful implications for health professionals. PMID- 17729131 TI - Sexual coercion, HIV-related risk, and mental health among female sex workers in China. AB - We performed this study to examine the association of sexual coercion with HIV related risk behaviors and suicidal thoughts and attempts among female sex workers (FSWs) in Guangxi, China. Four hundred fifty-four FSWs in 57 entertainment establishments (including shampooing salons, massage parlors, and restaurants) were interviewed between March and May 2004. Fifteen percent of the women reported having been coerced into sex in the last 6 months. The prevalence of suicidal thoughts and suicide attempts in the last 6 months were 14.3% and 8.4%, respectively. Sexual coercion was significantly associated with both an increased rate of HIV-related risk behavior, and suicidal thoughts and attempts among FSWs. Therefore, along with the awareness and intervention programs, efforts should be taken to reduce the exposure of FSWs to sexual coercion and to improve the mental health of FSWs. PMID- 17729133 TI - Trends in injury-related deaths before and after dissolution of the Union of Soviet Socialist Republics. AB - The relationship of death rates due to injury with the dissolution of the Soviet empire deserves special focus because of the impact of injury deaths on the productive working population between the ages of 15 and 65 years. A retrospective review was performed of annual mortality rates due to intentional and unintentional injuries, using WHO data from 1980 to 2003. Using data from a comparison group in Western Europe, the nations of the former Union of Soviet Socialist Republics (USSR) were studied. Annual death rates were examined using polynomial regression after 3-year moving averages smoothed the plots. The majority of trends in injury-related death noted in the comparison group decreased constantly over time. In contrast, many nations of the former USSR experienced an initial decrease, reaching a nadir in 1985 - 1987, followed by an increase in injury-related deaths. Moreover, many of these nations experienced a subsequent decrease following the dissolution of the USSR in 1991. The monitoring of trends in injury mortality in countries experiencing social and political upheavals is warranted. PMID- 17729134 TI - Injury mortality in local communities in Sweden and in the three Baltic States: implications for prevention. AB - This study provides a comparative time-trend evaluation of injury mortality in local communities in Sweden and the three Baltic States, considering their national socio-political and economic situations and with analysis of local injury prevention structures and activities. Data for the period from 1990 to 2002 were gathered from national statistical offices for the cities of Boras, Tartu, Jelgava and Kaunas and from WHO databases for national level analyses. The death rates for Boras remained relatively stable over the time period, while the Baltic communities had increasing rates until 1994 and seemed to stabilize after 1997. The differences in injury mortality in the studied communities were highest for the 0 - 19 year age group and especially in the 20 - 64 year age group, but not for the 65+ year age group. Local communities in the Baltic States should consider coordinated safety promotion and injury prevention programmes as a complement to national safety promotion framework. PMID- 17729135 TI - Road traffic mortality in Estonia: alcohol as the main contributing factor. AB - Traffic fatalities are the leading cause of death among the young and middle-aged population in Estonia. The objective of this study was to reveal the pattern of traffic fatalities among the population aged 15 - 64 years and to determine the role of alcohol in their fatalities. The data were collected from post-mortem reports at the Estonian Bureau of Forensic Medicine from 2000 to 2002. Alcohol related deaths were those with a blood alcohol concentration (BAC) equal or above 0.05 g/100 ml. Out of 512 victims, 401 were males and 111 were females. The greatest group were car occupants (58%) followed by pedestrians (31%). The portion of alcohol-related deaths was 70% among men and 44% among women. The mean BAC and percentage of alcohol-related deaths was significantly higher in pedestrian than in driver fatalities. Alcohol intoxication was identified as the most powerful contributing factor to traffic fatalities. The results provide more evidence for politicians to tackle alcohol abuse and unsafe traffic environments. PMID- 17729136 TI - Effects of driver nationality and road characteristics on accident fault risk. AB - This paper investigates the combined effect of driver nationality and several road characteristics (area type, at or not at junction, lighting conditions) on accident fault risk. Data from the national accident database of Greece are used to calculate accident relative fault risk rates under induced exposure assumptions. A log-linear analysis is then used to examine first- and higher order effects within three or more variable groups. The examination of the second order interaction among the accident fault risks of various driver nationalities at or not at junction was found to be significant. On the contrary, the respective combined effects of area type and lighting conditions were found to be non-significant. It was also shown that roadway features do not affect accident fault risk in a combined way. Results clearly indicate that foreign drivers in Greece are at increased risk. Moreover, foreign nationalities corresponding to permanent residents (i.e. Greeks and Albanians) appear to be at lower fault risk compared to foreign nationalities corresponding to tourists and visitors (e.g. EU Nationals). The effects of the various road characteristics do not modify these general trends. PMID- 17729137 TI - Impact of lowering the legal blood alcohol concentration limit to 0.03 on male, female and teenage drivers involved alcohol-related crashes in Japan. AB - In June of 2002, a revision to part of the Road Traffic Act drastically increased the penalties for drinking and driving offences in Japan. Most notably, the legal blood alcohol concentration (BAC) limit for driving was lowered from 0.05 mg/ml to 0.03 mg/ml. The rationale for the new lower BAC limit was predicated on the assumption that drinking drivers will comply with the new, lower limit by reducing the amount of alcohol they consume prior to driving, thereby lowering their risk of crash involvement. This, in turn, would lead to fewer alcohol related crashes. A key limitation of previous lower BAC evaluation research in determining the effectiveness of lower legal BAC limit policies is the assumption of population homogeneity in responding to the laws. The present analysis is unique in this perspective and focuses on the evaluation of the impact of BAC limit reduction on different segments of the population. The chief objective of this research is to quantify the extent to which lowering the legal limit of BAC has reduced male, female and teenager involvement in motor vehicle crashes in Japan since 2002. Most notably, the introduction of reduced BAC limit legislation resulted in a statistically significant decrease in the number of alcohol impaired drivers on the road in Japan, indicating responsiveness to the legal change among adults and teenagers. In addition, this preliminary assessment appears to indicate that the implementation of 0.03 BAC laws and other associated activities are associated with statistically significant reductions in alcohol involved motor vehicle crashes. In comparison, the rates of total crashes showed no statistically significant decline nor increase in the period following the introduction of the BAC law, indicating that the lower BAC limit only had an effect on alcohol-related crashes in Japan. The evidence suggests that the lower BAC legal limit and perceived risk of detection are the two most important factors resulting in a sustained change in drinking and driving behaviour in Japan. It is recommended that future research and resources in other countries be focused on these factors as determinants to reduced alcohol-related crashes. PMID- 17729138 TI - Towards safe environments for youth sports: impact of a fair play programme on injury rates in youth bandy. PMID- 17729139 TI - An analysis of sport-related injuries: British Columbia children's hospital Emergency Department 1999 - 2003. PMID- 17729140 TI - Analysis of paediatric injuries related to child restraint seats: are children at higher risk of injury outside the vehicle than inside? PMID- 17729141 TI - The role of the ministry of health in preventing injuries and violence. PMID- 17729143 TI - Language and communication difficulties in juvenile offenders. AB - BACKGROUND: Studies of the prison population suggest that the numbers of prisoners with language and communication disorders is higher than that of the overall population. However, the prison population is heterogeneous and it is important to focus on specific areas of the population. This study focuses on juvenile offenders. AIMS: The study aimed to screen language and communication skills in half the population of an establishment for juvenile offenders aged 15 17 years. METHODS & PROCEDURES: A total of 58 participants were selected at random and screened on the oral subtests of the Test of Adolescent and Adult Language, 3rd Edn (TOAL-3), the British Picture Vocabulary Scale (BPVS-II) and the Test for Reception of Grammar: Version 2 (TROG-2). Literacy and numeracy information was also obtained. OUTCOMES & RESULTS: The mean age of the group was 17 years; 19 were looked-after children; and 90% had ceased to attend school before age 16. On the TOAL-3 subtests, 66-90% of juvenile offenders in the sample had below average language skills, with 46-67% of these being in the poor or very poor group. None of the participants reached their age equivalence on the BPVS, but most of them reached the 12-year and above threshold on the TROG. A total of 62% of the sample had not achieved Level 1 in literacy. The findings suggest that these young people may not have the necessary skills to cope with verbally mediated interventions aimed at reducing re-offending. CONCLUSIONS: The results suggest that speech and language therapy assessment should be available to juvenile offenders with speech and language therapy intervention available to those found to have language and communication difficulties. There are also implications for speech and language therapy provision to young people who are not engaged within the education system. The TOAL-3 appears to be a useful screening instrument for this population, but a number of issues around the suitability of assessments for this population are discussed. PMID- 17729144 TI - Analysis of formant frequencies in patients with oral or oropharyngeal cancers treated by glossectomy. AB - AIMS: To compare voice quality as defined by formant analysis using a sustained vowel in patients who have undergone a partial glossectomy with a group of normal subjects. METHODS & PROCEDURES: The design consisted of a single centre, cross sectional cohort study. The setting was an Adult Tertiary Referral Unit. A total of 26 patients (19 males) who underwent partial glossectomy and 31 normal volunteers (18 males) participated in the study. Group comparisons using the first three formant frequencies (F1, F2 and F3) using linear predictive coding (Laryngograph Ltd, London, UK) were performed. The existence of any significant difference of F1, F2 and F3 between the two groups using the sustained vowel /i/ and the effects of other factors, namely age, first presentation versus recurrence, site (oral cavity, oropharynx), subsite (anterior two-thirds of the tongue, tongue base), stage, radiation, complication, and neck dissection, were analysed. OUTCOMES & RESULTS: Formant frequencies F1, F2 and F3 were normally distributed. F1 and F2 were significantly different in normal males versus females. F1, F2 and F3 were not different statistically between male and female glossectomees. Comparison of only women showed significant differences between normal subjects and patients in F2 and F3, but none in F1. This was the opposite in men where F1 was significantly different. Age, tumour presentation, site, subsite, radiation and neck dissection showed no significant difference. Postoperative complications significantly affected the F1 formant frequency. CONCLUSIONS: The study found that the formant values in patients following a partial glossectomy were altered significantly as compared with the normal control subjects. Only gender and complications and not the age, site, subsite, radiation and neck dissection were seen to influence the formant scores. PMID- 17729145 TI - Parents' and speech and language therapists' explanatory models of language development, language delay and intervention. AB - BACKGROUND: Parental and speech and language therapist (SLT) explanatory models may affect engagement with speech and language therapy, but there has been dearth of research in this area. This study investigated parents' and SLTs' views about language development, delay and intervention in pre-school children with language delay. AIMS: The aims were to describe, explore and explain the thoughts, understandings, perceptions, beliefs, knowledge and feelings held by: a group of parents from East Manchester, UK, whose pre-school children had been referred with suspected language delay; and SLTs working in the same area, in relation to language development, language delay and language intervention. METHODS & PROCEDURES: A total of 24 unstructured interviews were carried out: 15 with parents whose children had been referred for speech and language therapy and nine with SLTs who worked with pre-school children. The interviews were transcribed verbatim and coded using Atlas/ti. The data were analysed, subjected to respondent validation, and grounded theories and principled descriptions developed to explain and describe parents' and SLTs' beliefs and views. OUTCOMES & RESULTS: Parent and SLT data are presented separately. There are commonalities and differences between the parents and the SLTs. Both groups believe that language development and delay are influenced by both external and internal factors. Parents give more weight to the role of gender, imitation and personality and value television and videos, whereas the SLTs value the 'right environment' and listening skills and consider that health/disability and socio economic factors are important. Parents see themselves as experts on their child and have varied ideas about the role of SLTs, which do not always accord with SLTs' views. The parents and SLTs differ in their views of the roles of imitation and play in intervention. Parents typically try strategies before seeing an SLT. CONCLUSIONS: These data suggest that parents' ideas vary and that, although parents and SLTs may share some views, there are some important differences. These views have implications for the provision of appropriate services. Although this is a small sample from one group in the UK, the results indicate the need to investigate the views of other groups of parents. PMID- 17729146 TI - On-line processing of wh-questions in children with G-SLI and typically developing children. AB - BACKGROUND: The computational grammatical complexity (CGC) hypothesis claims that children with G(rammatical)-specific language impairment (SLI) have a domain specific deficit in the computational system affecting syntactic dependencies involving 'movement'. One type of such syntactic dependencies is filler-gap dependencies. In contrast, the Generalized Slowing Hypothesis claims that SLI children have a domain-general deficit affecting processing speed and capacity. AIMS: To test contrasting accounts of SLI we investigate processing of syntactic (filler-gap) dependencies in wh-questions. METHODS & PROCEDURES: Fourteen 10;2 17;2 G-SLI children, 14 age-matched and 17 vocabulary-matched controls were studied using the cross-modal picture-priming paradigm. OUTCOMES & RESULTS: G-SLI children's processing speed was significantly slower than the age controls, but not younger vocabulary controls. The G-SLI children and vocabulary controls did not differ on memory span. However, the typically developing and G-SLI children showed a qualitatively different processing pattern. The age and vocabulary controls showed priming at the gap, indicating that they process wh-questions through syntactic filler-gap dependencies. In contrast, G-SLI children showed priming only at the verb. CONCLUSIONS: The findings indicate that G-SLI children fail to establish reliably a syntactic filler-gap dependency and instead interpret wh-questions via lexical-thematic information. These data challenge the Generalized Slowing Hypothesis account, but support the CGC hypothesis, according to which G-SLI children have a particular deficit in the computational system affecting syntactic dependencies involving 'movement'. As effective remediation often depends on aetiological insight, the discovery of the nature of the syntactic deficit, along side a possible compensatory use of semantics to facilitate sentence processing, can be used to direct therapy. However, the therapeutic strategy to be used, and whether such similar strengths and weaknesses within the language system are found in other SLI subgroups are empirical issues that warrant further research. PMID- 17729147 TI - Narrative in adolescent specific language impairment (SLI): a comparison with peers across two different narrative genres. AB - BACKGROUND: Narrative may provide a useful way in which to assess the language ability of adolescents with specific language impairment and may be more ecologically valid than standardized tests. However, the language of this age group is seldom studied and, furthermore, the effect of narrative genre has not been explored in detail. METHODS & PROCEDURES: A total of 99 typically developing adolescents and 19 peers with specific language impairment were given two different types of narrative task: a story-telling condition and a conversational condition. Four areas of narrative (productivity, syntactic complexity, syntactic errors and performance) were assessed. OUTCOMES & RESULTS: The group with specific language impairment was poorer on most aspects of narrative confirming recent research that specific language impairment is a long-term disorder. A number of measures also showed interactions between group and genre, with story telling proving to be a disproportionately more difficult task for the specific language impairment group. Error analysis also suggested that the specific language impairment group was making qualitatively different errors to the typically developing group, even within a genre. CONCLUSIONS: Adolescents with specific language impairment are not only poorer at both types of narrative than peers, but also show different patterns of competence and error, and require more support from the narrative-partner. CLINICAL IMPLICATIONS: Assessments of adolescents are less frequent than at younger ages. This is partly because of the sparsity of tests available in this age range. Qualitative analysis of narrative might prove a useful alternative. The findings suggest that in every-day conversation, young people with specific language impairment manage their difficulties more discreetly and this might make them harder to identify in a mainstream setting. PMID- 17729151 TI - Analysis of fractal and fast fourier transform spectra of human electroencephalograms induced by odors. AB - Fast Fourier transform (FFT) and fractal dimension (FD) are computed to discover the evoked potentials (EPs) in the base human electroencephalograms (EEGs) corresponding to six types of odor inhalation, one at a time. During the first 20 s of the EEG recording, the patient breathes normally and the rest of the recording time 21-64 s, inhales an odor, when both the eye open and closed modes. FFT spectral analysis cannot discriminate the potential due to olfactory stimuli from the base EEG. However, fractal spectra analysis predicts the evoked potential due to inhalation of English rose, jasmine, lemon, orange, rose garden, and sandalwood concentrates. Similar results are obtained for three of the patients examined and on computing for five EEG recordings of two patients during inhalation of six types of odor. PMID- 17729152 TI - Microscopic analysis of the different regions of three Alzheimer brains aged 93, 94, and 104 years old. AB - The brains of three Alzheimer patients aged 93, 94, and 104 years old were analyzed. Although cell death was apparent in different cortices, the prefrontal cortex and the Broca's appeared to be hit hardest. The different CA areas of the hippocampal formation all displayed equivalent degrees of cell death but the entorhinal areas showed the most severe degree of cell degeneration. Both apoptosis and necrosis were observed in the different cerebral regions of these very old patients, as expected. PMID- 17729148 TI - Assertive and responsive conversational skills of Italian-speaking late talkers. AB - BACKGROUND: Previous research on the pragmatic abilities of late talkers at 24 months of age indicates that they have difficulties initiating conversational interactions, but possess intact responsiveness skills. This study uses a parent administered questionnaire for evaluating the conversational skills of late talkers and suggesting pragmatic intervention goals. AIM: To examine the conversational assertiveness and responsiveness of late talkers at 2 years of age. METHODS & PROCEDURES: A parent report measure, The Social Conversational Skills Rating Scale-Italian version, was administered to 30 parents of late talkers, 30 parents of typically developing children matched for age, and 30 parents of younger, typically developing children matched for vocabulary size. OUTCOMES & RESULTS: The late talkers received significantly lower ratings for both assertiveness and responsiveness in comparison with their age-matched peers. They did not differ significantly from the younger, vocabulary-matched group. Assertiveness and responsiveness mean ratings were positively correlated with vocabulary size for the age-matched group, but not for either of the other two groups. CONCLUSIONS: This study confirms a delay in the development of late talkers' social-conversational skills. An investigation of individual profiles suggests that some late talkers may require goals for vocabulary development as well as independent goals for developing pragmatic skills. PMID- 17729154 TI - Specific mechanism for blood inflow stimulation in brain area prone to Alzheimer's disease lesions. AB - The present study describes the specific two-stage mechanism that intensifies blood supply to the brain area comprising amygdala, hippocampus, olfactory bulb, entorhinal cortex, and neocortex (AHBC). Cholinergic neurons from the nuclei of basal forebrain induce vasodilatory effect through release of acetylcholine. In physiological aging the efficacy of this neuronal system declines, while intensive formation of amyloidogenic peptides starts. These peptides at low, picomolar concentrations activate alpha7 nicotinic acetylcholine receptors, thus enhancing angiogenesis and in so doing restoring blood supply to the AHBC area. PMID- 17729153 TI - Lateral and vertical attentional biases in normal individuals. AB - BACKGROUND: When normal people attempt to bisect lines they often make their mark to the left of midline (pseudoneglect) and when attempting to bisect radial lines normal people tend to bisect distal to the actual midline. These biases might be related to asymmetrical activation induced by making spatial computations or attention-intentional preferences. The purpose of this study was to learn if in the absence of spatial computations normal subjects would demonstrate a left and upward bias. METHODS: Normal subjects (139) were given 8 pegs and asked to place these pegs anywhere on a 2-foot-square board. RESULTS: Overall, the subjects displaced the pegs to the left and upward. CONCLUSIONS: The overall left-distal bias observed in this experiment was not induced by spatial computation or misperceptions, but is consistent with the postulate that the right hemisphere is dominant for attention-intention and has a relatively distal bias. PMID- 17729155 TI - Effects of testosterone and growth hormone on long-term retention and extinction of a passive avoidance response in young and aged rats. AB - Wistar rats were divided into two blocks: young and aged. Each block was then randomly divided into the following groups: (1) Control (saline solution), (2) Growth Hormone (GH), (3) Testosterone enanthate, and (4) GH plus testosterone enanthate. Animals were trained on a one-trial passive avoidance conditioning and tested for retention 24 h after training and thereafter twice a week until the extinction response occurred. Results showed that GH, testosterone, and GH plus testosterone improved long-term memory in young rats. Both GH and testosterone delayed the extinction process in young and aged rats. The GH-testosterone interaction delayed the extinction only in young rats. PMID- 17729156 TI - Effects of botulinum toxin on strength-duration properties. AB - Axonal excitability studies have been used in several diseases to investigate the underlying pathophysiology. The threshold tracking technique was developed to measure noninvasively several indices of axonal excitability, such as strength duration properties. This study investigated the possible effects of botulinum toxin on strength-duration time constant (SDTC) in patients with the symptoms and signs of botulism. The clinical and electrophysiological findings of 13 patients who were admitted to the authors' clinic with botulism signs and symptoms were evaluated in a 5-day period after exposure to the toxin prospectively. After routine diagnostic electroneuromyographic examinations and electromyogram with repetitive nerve stimulation at 20-50 Hz, SDTC was studied. The results were compared with 13 age- and sex-matched healthy volunteers. The SDTCs were 381 +/- 60 micros and 471 +/- 84 micros in patients and controls, respectively. There was a statistical difference between the two groups (p = .003, Mann Whitney U test). These findings suggest a possible effect of botulinum toxin, known to be effective at neuromuscular junction, on Na(+)/K(+) pump activity, and Na(+) or K(+) conductance. PMID- 17729157 TI - Medroxyprogesterone acetate induces c6 glioma chemosensitization via antidepressant-like lysosomal phospholipidosis/myelinosis in vitro. AB - The authors have previously shown that medroxyprogesterone acetate (MPA) inhibits growth and increases drug sensitivity in C6 glioma with myeloid bodies. Myeloid bodies can occur in cells either due to robust toxicity with mitochondrial membrane disruption or due to milder events such as seen in lysosomal phospholipidosis. Exact patterns of myelinosis accompanying to MPA chemo sensitization is important, because uncoupling of nuclear versus mitochondrial toxicity of anti-neoplastics by MPA would lead to safer employment of glioma chemotherapy with reduced neurotoxicity. By monitoring and comparing cell kinetics with fine structural features of cell death, the authors estimated subcellular effects accompanying growth-inhibitory drug actions in C6 glioma. The analysis revealed that MPA induced mainly lysosomal phospholipidosis, while inhibiting clonogenicity alone and augmenting procarbazine efficacy. It induced apoptosis in combination with cisplatin. It reduced mitochondrial-damage-based early cytotoxicity of methotrexate, yet it did not hinder its anti-clonogenic efficacy. Progesterone analogues - similar to antidepressants - inhibit cholesterol esterification, and this efficacy relates with their P-glycoprotein inhibition. Reducing esterification and plasma-membrane localization of cholesterol may lead MPA induction of lysosomal phospholipidosis, growth indolency, and drug sensitization in glioma. PMID- 17729158 TI - Cellular analysis of S100Beta and fibroblast growth factor-2 in the dorsal root ganglia and sciatic nerve of rodents. focus on paracrine actions of activated satellite cells after axotomy. AB - The role of satellite cells, a type of peripheral glia, in the paracrine mechanisms related to neuronal maintenance and plasticity in the dorsal root ganglia (DRG) needs to be further investigated. This study employed immunohistochemistry and image analysis to investigate basic fibroblast growth factor (bFGF, FGF-2) and S100Beta immunoreactivities in the DRG and sciatic nerve of the rat and mouse. Well-characterized antibodies against bovine (residues 1 24) and rat (residues 1-23) FGF-2 were employed. Furthermore, the state of satellite cell reaction and changes in the FGF-2/S100Beta immunoreactivity were analyzed after axotomy of rat sciatic nerve. Scattered neurons and the majority of the satellite cells of the rat DRG and also Schwann cells of the rat sciatic nerve stained for S100Beta. In the mouse, strong S100Beta was encountered in the majority of sensory neurons and Schwann cells. Moderate FGF-2 (residues 1-24) immunoreactivity was found in scattered small size neurons of the rat DRG. A strong FGF-2 (residues 1-23) immunoreactivity was achieved in the satellite cells of rat DRG. Both FGF-2 antisera showed strong labeling in the mouse DRG sensory neurons. Activated satellite cells of the axotomized DRG possessed increased amount of FGF-2 and S100Beta immunoreactivity as demonstrated by quantitative image analysis. The proximal stump of the lesioned rat sciatic nerve showed increased FGF-2 (residues 1-24 and 1-23) in the Schwann cells, myelin sheaths, and neuronal fibers, without changes in the level of S100Beta immunoreactivity. Results suggested a possible interaction between FGF-2 and S100Beta in activated satellite cells of the DRG, which might trigger paracrine actions in the axotomized sensory neurons. PMID- 17729159 TI - gamma-H2AX foci formation in peripheral blood lymphocytes of tumor patients after local radiotherapy to different sites of the body: dependence on the dose distribution, irradiated site and time from start of treatment. AB - PURPOSE: To evaluate the relationship between an estimated integral total body radiation dose delivered and phosphorylated histone H2AX protein (gamma-H2AX) foci formation in peripheral blood lymphocytes of cancer patients. MATERIAL AND METHODS: gamma-H2AX formation was quantified as the mean number of foci per lymphocyte (N(meanH2AX)) and the percentage of lymphocytes with > or =n foci. The integrated total body radiation dose was estimated from the dose volume histogram of patient's body corrected for the proportion of the body scanned by computed tomography for 3D treatment planning. RESULTS: There was a strong linear correlation between the mean number of gamma-H2AX foci per lymphocyte in the peripheral blood sample and integrated total body radiation dose (r = 0.83, p < 0.0001). The slope of the relationship was dependent on the site of body irradiated. In comparison to chest irradiation with a slope of 8.7 +/- 0.8 foci Gy(-1), the slopes for brain, upper leg and pelvic sites were significantly shallower by -4.7, -4.3, and -3.8 Gy(-1), respectively (p < 0.0001), while the slope for upper abdomen irradiation was significantly larger by 9.1 +/- 2.6 Gy( 1) (p = 0.0007). There was a slight time effect since the start of radiotherapy on the slopes of the in vivo dose responses leading to shallower slopes (-1.5 +/- 0.7 Gy(-1), p = 0.03) later (> or =10 day) during radiotherapy. After in vitro irradiation, lymphocytes showed 10.41 +/- 0.12 foci per Gy with no evidence of inter-individual heterogeneity. CONCLUSIONS: gamma-H2AX measurements in peripheral lymphocytes after local radiotherapy allow the estimation of the applied integral body dose. The site and time dependence have to be considered. PMID- 17729160 TI - Mechanisms underlying the radioprotective effect of histamine on small intestine. AB - PURPOSE: To examine the protective effects of histamine on intestinal damage produced by gamma-radiation. MATERIALS AND METHODS: 56 mice were divided into 4 groups. Histamine and Histamine-10 Gy groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 20 hours before irradiation and continued until the end of the experimental period; the untreated group received saline. Histamine-10 Gy and untreated-10 Gy groups were irradiated with a single dose on whole-body using Cesium-137 source (7 Gy/min) and were sacrificed 3 days after irradiation. Small intestine was removed, fixed and stained with hematoxylin and eosin. The number of intestinal crypts per circumference, and other histological characteristics of intestinal cells were evaluated. We further determined by immunohistochemistry the expression of proliferating cell nuclear antigen (PCNA), Bax, Bcl-2 (pro- and anti-apoptotic protein, respectively), antioxidant enzymes (Superoxide dismutase (SOD), Catalase and Glutathione peroxidase), histamine content and apoptosis by terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick end labeling (TUNEL) assay. Cells in the S phase of the cell cycle were identified by immunohistochemical detection of 5-bromo-2'-deoxyuridine (BrdU) incorporation. RESULTS: Histamine treatment reduced mucosal atrophy, edema and preserved villi, crypts and nuclear and cytoplasmic characteristics of small intestine after radiation exposure. Additionally, histamine treatment increased PCNA expression and the BrdU-positive cell number, histamine content, decreased the number of apoptotic cells and significantly increased Catalase and copper-zinc-containing SOD of irradiated mice. CONCLUSIONS: Histamine prevents radiation-induced toxicity by increasing proliferation of damaged intestinal mucosa and suppressing apoptosis that was associated with an increase in SOD and Catalase levels. This effect might be of clinical value in patients undergoing radiotherapy. PMID- 17729161 TI - Matrix-Metallo-Proteinases and their tissue inhibitors in radiation-induced lung injury. AB - PURPOSE: Remodeling of extracellular matrix (ECM) after lung damage depends on collagen degrading Matrix-Metallo-Proteinases (MMP) and their endogenous inhibitors (Tissue-Inhibitors of Metallo-Proteinases, TIMP). Transforming growth factor (TGF)-beta1 has been implicated in the pathogenesis of radiation-induced lung fibrosis upon its effects on fibroblast proliferation and collagen synthesis. Lung cancer patients have often elevated TGF-beta1 plasma levels as a result of increased TGF-beta1 expression in their tumours. On this background, we investigated the effect of irradiation on the MMP/TIMP system in the lung tissue of normal and transgenic TGF-beta1 mice, in which TGF-beta1 is overexpressed in the liver resulting in high TGF-beta1 plasma levels. MATERIAL AND METHODS: Transgenic (TG) and wild-type (WT) mice underwent thoracic irradiation with 12 Gy or sham-irradiation. For each study group (TG 12 Gy; TG 0 Gy; WT 12 Gy; WT 0 Gy) 8 mice were sacrificed at 4 and 8 weeks after (sham-) irradiation. The TGF-beta1, TIMP-1/-2/-3 expression in the lung tissue was quantified by Western blot; the MMP-2 and MMP-9 activity was analysed by zymography. The cellular origin of the MMP and TIMP was localised by immunohistochemistry. RESULTS: Irradiation had no influence on the TIMP-1/-2/-3, but increased significantly the MMP-2 /-9 expression. In the lung tissue of TG mice the TIMP-1/-2/-3 expression was elevated, the MMP-9 activity was decreased. The immunhistochemical study showed that parenchymal and inflammatory cells express these MMP/TIMP. CONCLUSION: Our results provide evidence that the overexpression of MMP-2 and MMP-9 is involved in the inflammatory response of radiation-induced lung injury. MMP-2 and MMP-9 are known to degrade collagen IV of basement membranes, therefore affecting the structural integrity of lung tissue. In contrast, in lung tissue of TG mice the TIMP-1/-2/-3 expression was up-regulated and the MMP-9 activity was diminished, thereby decreasing possibly the ECM degradation leading to lung fibrosis. PMID- 17729163 TI - Strand breaks induced in plasmid DNA by ultrasoft X-rays: influence of hydration and packing. AB - PURPOSE: To study the effect of hydration level and plasmid packing on strand break induction in DNA by ultrasoft X-ray. MATERIALS AND METHODS: Bluescript (pBS, tight packing) and pSP189 (pSP, loose packing) plasmids were irradiated by 250, 380, and 760 eV ultrasoft X-rays at the Laboratoire pour l'Utilisation du Rayonnement Electromagnetique synchrotron facility (Orsay, France). Single and double strand breaks (SSB and DSB) were quantified by gel electrophoresis. RESULTS: The number of DSB per Gray and per Dalton in pBS plasmids were (5.6 +/- 0.1), (6.3 +/- 0.1) and (8.5 +/- 0.4)x10(-12) at 250, 380 and 760 eV, respectively. They were respectively 1.4 +/- 0.1, 1.1 +/- 0.1 and 1.9 +/- 0.2 times larger for pSP plasmids. SSB/DSB ratios varied between 4.4 and 6.4. CONCLUSION: The observed dependency of strand break induction by ultrasoft X-rays on the hydration level of DNA in plasmids films may be associated with: (i) Damage transfer from the water shell to the DNA and/or (ii) change in packing. 760 eV photons which are more often absorbed in the hydration shell and yield longer range electrons than 250 and 380 eV photons, induce more DSB per Gray and per Dalton, especially for the looser plasmid (pSP). PMID- 17729164 TI - Effect of Boron Neutron Capture Therapy (BNCT) on normal liver regeneration: towards a novel therapy for liver metastases. AB - PURPOSE: The effect of Boron Neutron Capture Therapy (BNCT) on normal liver regeneration was examined in the Wistar rat. The model used is clinically relevant to a novel technique proposed for the treatment of multifocal non resectable liver metastases in man. The success of the technique also requires that BNCT should not significantly impair regeneration of normal hepatocytes. MATERIALS AND METHODS: The effect of therapeutic doses of boronophenylalanine (BPA), GB-10 (Na(2)(10)B(10)H(10)) and (GB-10 + BPA) and of BNCT mediated by these boron delivery agents on normal liver regeneration and liver function in the Wistar rat was examined using partial hepatectomy as the regenerative stimulus. The end-points evaluated were body weight, liver weight/body weight ratio, DNA synthesis in terms of 5-bromo-2'-deoxyuridine incorporation, hemogram, kidney function in terms of blood urea nitrogen and creatinine levels, liver function in terms of serum albumin, total and direct bilirubin and liver enzymes (alanine transaminase and aspartate transaminase) and liver histology/architecture. RESULTS: BNCT mediated by BPA, GB-10 or (GB-10 + BPA) did not cause alterations in the outcome of normal liver regeneration, regenerated liver function/proliferation or histology/architecture. CONCLUSION: The BNCT protocols, at the physical doses selected, did not impair the capacity of normal liver hepatocytes to regenerate. PMID- 17729165 TI - Increased expression of nuclear NF-kappaB after coronary artery balloon injury can be inhibited by intracoronary beta-irradiation. AB - PURPOSE: Molecular mechanisms by which balloon angioplasty injury-induced neointimal hyperplasia can be reduced by intravascular brachytherapy are unclear. We investigated the role of nuclear factor-kappaB (NF-kappaB) in neointimal hyperplasia following intracoronary irradiation. MATERIALS AND METHODS: Fifty four coronary arteries from 30 pigs were divided into 6 groups: sham control, balloon angioplasty injury alone, beta-irradiation at doses of 14 or 20 Gy, and 14 or 20 Gy beta-irradiation immediately followed by balloon injury. Coronary arteries were injured by overstretch balloon angioplasty and then the arteries were irradiated using a Rhenium-188 ((188)Re) beta-emitting solution-filled balloon. Pigs were scarified one day or one week after coronary interventions for molecular detection and six weeks after the procedures for histological examination. RESULTS: Six weeks after coronary interventions, the histological results show that balloon angioplasty injury had induced intimal hyperplasia in coronary artery but the response was significantly reduced by 28% and 60% when the injury was immediately treated by 14 and 20 Gy (188)Re beta-irradiation, respectively. The expression of arterial NF-kappaB p65, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were detected at one day and one week after the procedures. The treatment of balloon injury could significantly induce the NF-kappaB p65 expression in both gene and protein levels, and such induction could be significantly reduced by (188)Re beta irradiation at dose of 20 Gy. However, the similar result on the regulation of gene expression affected by the beta-irradiation could not be observed in ICAM-1 and VCAM-1. CONCLUSION: The inhibitory effect of intracoronary brachytherapy on neointimal formation following overstretch balloon angioplasty could involve inhibition of NF-kappaB p65. PMID- 17729166 TI - CalcNTCP: a simple tool for computation of normal tissue complication probability (NTCP) associated with cancer radiotherapy. AB - PURPOSE: This study was aimed to develop a simple and user-friendly software for fast and accurate computation of normal tissue complication probability (NTCP) in accordance with the Lyman model. MATERIALS AND METHODS: The software CalcNTCP has been developed in Visual Basic and is equipped with two functional modes. Mode 1 is based on pre-stored values of various parameters for 27 different organ systems and the user has only to input the values of volume fraction (v) and radiation dose (D), whereas Mode 2 is designed for the customized entries. RESULTS: The results of software validation have demonstrated that CalcNTCP is more efficient and time-saving as compared to manual or semi-manual procedures. The shapes and locations of representative survival curves generated by CalcNTCP based computations for various radiation doses (10 - 100 Gy) and reference volumes (0.33 - 1.00) absolutely matched with optimal curves. CONCLUSION: CalcNTCP is a simple, fast and accurate tool for the computation of NTCP with a direct implication in the evaluation or optimization of radiotherapy treatment plans. PMID- 17729162 TI - Radiosensitization of human glioma cells by cyclooxygenase-2 (COX-2) inhibition: independent on COX-2 expression and dependent on the COX-2 inhibitor and sequence of administration. AB - PURPOSE: Patients with a malignant glioma have a very poor prognosis. Cyclooxygenase-2 (COX-2) protein is regularly upregulated in gliomas and might be a potential therapeutic target. The effects of three selective COX-2 inhibitors were studied on three human glioma cell lines. MATERIALS AND METHODS: The selective COX-2 inhibitors NS-398, Celecoxib and Meloxicam and three human glioma cell lines (D384, U251 and U87) were used. Cell growth was assessed by a proliferation assay, the interaction with radiation (0 - 6 Gy) was studied using the clonogenic assay and cell cycle distribution was determined by FACS (fluorescence-activated cell sorting) analysis. RESULTS: All COX-2 inhibitors reduced proliferation of the glioma cell lines irrespective of their COX-2 expression level. Incubation with 200 microM NS-398 24 h before radiation enhanced radiation-induced cell death of D384 cells and 750 microM Meloxicam resulted in radiosensitization of D384 and U87 cells. No radiosensitization was observed with COX-2 inhibitor administration after radiotherapy. Treatment of D384 with NS-398 (200 microM) or Celecoxib (50 microM) and U87 with NS-398 (200 microM) after radiation resulted even in radioprotection. CONCLUSIONS: Effectiveness of COX-2 inhibitors on cell proliferation and radio-enhancement was independent of COX-2 protein expression. The sequence of COX-2 inhibitor addition and irradiation is very important. PMID- 17729169 TI - Dangerous intimate partner relationships and women's mental health and health behaviors. AB - This study investigated the relationship between dangerousness in intimate partner relationships and victims' mental health and/or health behavior problems. Health records of 387 women residents in a domestic violence shelter in an urban city on the East coast were reviewed. Of these, 177 women were eligible for this study. Dangerousness was determined by Danger Assessment Score (DA). Higher DA scores were significantly associated with mental health symptoms and health behaviors, including anxiety (p = 0.0024), depression (p = 0.017), difficulty concentrating (p = 0.001), memory loss (p = 0.008), suicidal attempts (p = 0.013), weight gain (p = 0.014), past history of smoking (p = 0.027), and past history of illicit drug use (p = 0.047). PMID- 17729172 TI - Strategies for successful recruitment and retention of abused women for longitudinal studies. AB - Researchers agree that high recruitment and retention rates are essential for longitudinal studies and can be a daunting task. This paper examines retention rates for longitudinal studies of abused women and presents strategies to maximize recruitment and retention. The techniques presented resulted in subject retention rates of 89% to 100% in longitudinal prevalence, quasi-experimental, and randomized clinical trials that followed participants for up to 24 months. The findings point to the importance of establishing and sustaining collaborative partnerships with agencies, multiple contacts sources with study participants, incremental monetary incentives, and a detailed field tracking protocol that includes safety practices. PMID- 17729170 TI - Abuse and psychosocial stress as factors in high utilization of medical services during pregnancy. AB - High utilization of medical services during pregnancy has not been described as most studies have focused on women who receive inadequate or no prenatal care. This paper describes the characteristics and medical utilization data of 500 pregnant women enrolled in a prospective study. High utilizers (HU), who had a mean of 7.8 utilizations (SD = 3.2), were significantly more likely to be nonwhite, low income, and younger than low utilizers (LU) who had a mean of 0.99 utilizations (SD = 1.1). HU reported a 32% rate of recent abuse compared to 9% for LU. HU also reported significantly more stress, lower self-esteem, and more ambivalence about the pregnancy. Consistent with their higher utilization, they were more likely to be diagnosed with preterm labor, hyperemesis, and gestational diabetes. HU had a higher proportion of complaints of nausea, vomiting, diarrhea, and pain and more mental health diagnoses than LU. Overall, HU were a vulnerable group characterized by recent abuse, economic disadvantage, psychosocial stress, and mental health issues. Their high utilization of medical services may have been due in large part to unmet psychosocial needs. PMID- 17729171 TI - Assault history and follow-up contact of women survivors of recent sexual assault. AB - The purpose of this comparative descriptive study is to describe and examine differences in assault characteristics and the issues surrounding follow-up contact of women survivors of a recent sexual assault. This study identified assault characteristics: half of the assaults were by strangers; approximately one-third of the assaults occurred in the victim's home; 29% of the victims were abducted; weapons and physical force were used in over half of the cases; 63% were vaginal assaults; and 86% involved penile penetration. Three months after the assault and the initial examination, only 23% (n = 18) of the study participants could be contacted by telephone for follow-up. The study's findings provide not only data regarding the characteristics of sexual assault, but also the difficulties in contacting adult female survivors for follow-up services. Recommendations outline the importance of thorough, individualized examinations and the need for improved, timely, follow-up services for sexual assault victims. PMID- 17729173 TI - Talking about talk: the experiences of boys who survived intraparental homicide. AB - This article describes the experiences of men who experienced intraparental homicide (one parent killing the other parent) when they were boys. Twenty-one men were interviewed twice and data were analyzed using a hermeneutic approach. In this article we examine a topic that emerged as a core problem for these men, specifically, how they talked (or did not talk) about the homicide. Understanding intraparental homicide may provide information to guardians and professionals about what some male children need after such an event. PMID- 17729174 TI - The Domestic Violence Survivor Assessment (DVSA): a tool for individual counseling with women experiencing intimate partner violence. AB - The Domestic Violence Survivor Assessment (DVSA) was developed to measure survivor movement toward a violence free life over time. This paper reports our testing of the validity and reliability of the DVSA. Exploratory factor analysis (n = 162) found a single factor explaining 66% of the variance. Hierarchical multiple regression indicated that physical abuse severity, survivor and perpetrator substance abuse, economic and citizenship dependency, and children under 18 at home explained 10% of the variance p > .05. A second model examined the strength of interventions for survivors, controlling for influencing factors; R(2) was.24 (p < .001). The strongest interventions were individual counseling (p < .001) and resource referrals and other services (p < .05). The DVSA was found to have construct validity, sensitivity to change over time, and reliability. A county agency that adopted the DVSA evaluated its programs using the DVSA change scores and used this evaluation for program improvement. PMID- 17729175 TI - Psychiatric clinical nurse specialists, nurse practitioners, or the new practice doctorate: meeting patients' needs? PMID- 17729176 TI - Cultivating compassion across cultures. PMID- 17729178 TI - Internal consistency and factor analysis of the Dutch version of the Dizziness Handicap Inventory. AB - CONCLUSIONS: The Dutch (Belgium) translation of the Dizziness Handicap Inventory (DHI) has proven to be as consistent as the original version. In addition to the three original subscales, factor analysis revealed a fourth component scoring self-perceived effects of insufficient functioning of the vestibulo-ocular reflex (VOR). Focus should be on the DHI total score in order to compare future results with the existing literature. OBJECTIVE: To conduct a factor analysis and to determine its internal consistency. MATERIALS AND METHODS: Charts of 214 outpatients, referred with dizziness or imbalance of vestibular and non vestibular origin, were reviewed. RESULTS: The Cronbach's alpha coefficients for internal consistency were high for the total scale and good for the subscales. Corrected item-total correlations ranged from 0.71 for 'restricted travelling' to 0.29 for 'difficulties reading', when items were correlated with their respective subtotals, and ranged from 0.69 (restricted participation in social activities) to 0.33 (stressed relationships), when correlated with the total score. A principal component analysis with orthogonal rotation was conducted, suggesting a four-factor solution. Two factors were related to vestibular handicap, referring to the original functional and emotional subcategories. The remaining two factors related to vestibular disability, documenting motion sensitivity (original physical subscale) and insufficient VOR functioning. PMID- 17729179 TI - Middle ear pressure in preschool age children: influence of respiratory illness, season, and picornavirus or bacteria in the nasopharynx. AB - CONCLUSION: Middle ear pressure was affected by respiratory illness and season; picornavirus (without illness) or pathogenic bacteria in the nasopharynx had no or minor effect. OBJECTIVE: To examine the effect of respiratory illness, season, and nasopharyngeal microbial flora on middle ear pressure. SUBJECTS AND METHODS: Thirteen children were followed longitudinally with daily recording of respiratory symptoms, weekly tympanometry, and weekly testing of nasal aspirate/washes for Streptococcus pneumoniae, Hemophilus influenzae, Moraxella catarrhalis by culture and for picornavirus by RT-PCR. RESULTS: Abnormal middle ear pressure was present at 47% of 473 weekly visits by 11 preschool age ( 12 micromol/l) is a risk factor for several diseases of the central nervous system. Epidemiological studies have shown a dose-dependent relationship between concentrations of Hcy and the risk for neurodegenerative diseases. Hcy is a marker for B-vitamin deficiency (folate, B12, B6). Hyperhomocysteinemia (HHcy) causes hypomethylation which is an important mechanism that links Hcy to dementia. Supplementation with vitamins B aims at reducing the risk of neurodegenerative diseases. Current evidence suggests that Hcy-lowering treatment has a positive effect for the secondary and primary prevention of stroke. HHcy is very common in patients with Parkinson disease particularly those who receive L-dopa treatment. Furthermore, a positive association has been reported between HHcy and multiple sclerosis. Moreover, HHcy and vitamin B deficiency are reported to have a causal role in depression, and epilepsy. In addition several anti-epileptic drugs cause secondary HHcy. Therefore, sufficient intakes of the vitamins are recommended for patients who have already developed neuropsychiatric diseases. Vitamin B deficiency should be suspected in children with development disorders, failure to thrive and unexplained neurological manifestations. Elderly people are also an important at-risk group where vitamin B deficiency and HHcy have been linked to neurodegenerative diseases. Treatment with folate, B12, and B6 can improve cerebral function. Preventive vitamin B supplementation and sufficient intake seem very important for secondary and primary prevention of neuropsychiatric disorders, especially in subjects with a low intake or status of the vitamins. PMID- 17729192 TI - [Case reports, an important part of scientific publications]. PMID- 17729193 TI - [Mercury and Alzheimer's disease]. PMID- 17729194 TI - [Severe encephalitis without correlate in MRI]. AB - Encephalitis could be a life-threatening disease depending on localisation and infectious agent. Neuroimaging, especially MRI, is an important component in the diagnosis. The recent investigations demonstrate that diffusion abnormalities are the first and sensitive signs of viral encephalitis. We describe five patients with severe encephalitis with normal MR imaging. Three of five patients were intermittently mechanically ventilated, two of these longer than 4 weeks. The other two patients suffered from a severe psychosyndrome with seriously limited ability to communicate throughout 6 weeks. At the time of first MRI examination all patients were noticeably ill. Four of five patients had at least one follow up MRI. The MRI examinations included FLAIR sequences and DWI in four of five patients. Contrast-enhancement was detectable in none of our patients. Follow-up examinations revealed that symptoms of encephalitis were noticeably or completely regressive. PMID- 17729195 TI - [Clinical differential diagnosis of peripheral nerve compression syndromes]. PMID- 17729198 TI - [Eye disease and mode of delivery]. AB - Many ophthalmologists and obstetricians recommend either an assisted vaginal delivery with forceps or vacuum extraction or a Caesarean section in cases of pre existing eye diseases such as severe myopia, retinal detachment, diabetic retinopathy, or glaucoma. These recommendations, however, are not evidence-based. None of the published trials have reported any retinal changes after vaginal delivery. In general, eye disease is not an indication for an instrumental or operative delivery provided that regular eye examinations (once each trimester) have been performed. PMID- 17729199 TI - [Preconceptional health promotion and counselling pregnant women in choosing their obstetric clinic as further tools in the reduction of preterm deliveries]. AB - BACKGROUND: More than 100 000 women have already participated in the given BabyCare programme. It is highly accepted by pregnant woman, gynaecologists as well as the health insurance companies co-operating. Evaluation of the birth outcomes is done annually in comparison with a given perinatal data base. We look for further tools to reduce preterm deliveries. METHODS: Birth outcome is analysed based on a sample of 3 345 births documented by the gynaecologist controlled for age, parity, multiple gestation and education level. The preventive potentials of preconceptional interventions are exemplified and the given problems in the choice of obstetric clinics are summarized. RESULTS: Women participating in the BabyCare programme have a rate of preterm birth which is 20 to 25 % lower than in the control group. Additional preconceptional health promotion can reduce pregravid risk factors and provides many opportunities for preventive measures, which may reduce the incidence of severe complications substantially. Targeted counselling the choice of a clinic will additionally provide support for women with high risk pregnancies and may lead to a further reduction of complications or rather to a better management of incident complications. CONCLUSIONS: Health and nutritional counselling in early pregnancy by the BabyCare programme leads to a stable, significant, effective and efficient reduction of preterm births. The additional preconceptional and antepartal measures may contribute to a further reduction of complications. PMID- 17729200 TI - [The relationship between body weight, body height, body mass index and weight gain during pregnancy]. AB - BACKGROUND: The weight gain during pregnancy is influenced by maternal body weight and height. With this study we want to illustrate the relationship between weight, height, body mass index (BMI) and the weight gain in pregnancy. MATERIALS AND METHODS: Data of about 2.3 million singleton pregnancies were taken from the German perinatal statistics of 1995-2000. Weight gain was calculated as the difference between the weight at the end of the pregnancy and the weight at the first consultation. RESULTS: The distribution of the weight gain resembles a normal distribution. Overall mean weight gain is 12.8 kg. For women weighing < 63 kg, there is a rise in weight gain with increasing body weight at the first consultation. Beyond 63 kg the amount of weight gain falls with increasing body weight at the first consultation. Weight gain increases with increasing height. Overall there is a negative correlation between BMI and weight gain. However, women with the same BMI but different body weights and heights can differ significantly with regard to their weight gain. CONCLUSIONS: Height and body weight at the beginning of pregnancy are important determinants of the weight gain. They should therefore be used when assessing the weight gain in clinical practice. Use of the BMI, however, is not appropriate. We are investigating other ways of combining body weight and height. This will be discussed in a later publication. PMID- 17729201 TI - Consequences of intrauterine acidosis for early morbidity of term newborn infants. AB - OBJECTIVES: The study was designed to evaluate early morbidity of term newborn infants according to the umbilical artery pH and umbilical artery base excess. STUDY DESIGN: The study was based on the 1 173 infants who were born at term in the study period in 1997 with a UA-pH below 7.20. A retrospective review was carried out of maternal and infant records during the study period. All data were evaluated using SPSS for windows. RESULTS: Apgar-values and UA-pH correlated closely, the rate of 1-minute Apgar scores < 7 increased with decreasing UA-pH. The rate of 5-minute Apgar score < 7 increased strongly with UA-pH below 7.00. The study showed how closely UA-pH values are related to UA-BE values. Of newborns with UA-BE values of 0 to - 9 mmol / l 7 % had 1-minute Apgar scores < 7, 53 % of cases with UA-BE (15)N HSQC-IMPEACH and (13)C <--> (15)N HMBC-IMPEACH correlation spectra. AB - Utilization of long-range (1)H--(15)N heteronuclear chemical shift correlation has continually grown in importance since the first applications were reported in 1995. More recently, indirect covariance NMR methods have been introduced followed by the development of unsymmetrical indirect covariance processing methods. The latter technique has been shown to allow the calculation of hyphenated 2D NMR data matrices from more readily acquired nonhyphenated 2D NMR spectra. We recently reported the use of unsymmetrical indirect covariance processing to combine (1)H--(13)C GHSQC and (1)H--(15)N GHMBC long-range spectra to yield a (13)C--(15)N HSQC-HMBC chemical shift correlation spectrum that could not be acquired in a reasonable period of time without resorting to (15)N-labeled molecules. We now report the unsymmetrical indirect covariance processing of (1)H -(13)C GHMBC and (1)H--(15)N IMPEACH spectra to afford a (13)C--(15)N HMBC IMPEACH spectrum that has the potential to span as many as six to eight bonds. Correlations for carbon resonances long-range coupled to a protonated carbon in the (1)H--(13)C HMBC spectrum are transferred via the long-range (1)H--(15)N coupling pathway in the (1)H--(15)N IMPEACH spectrum to afford a much broader range of correlation possibilities in the (13)C--(15)N HMBC-IMPEACH correlation spectrum. The indole alkaloid vincamine is used as a model compound to illustrate the application of the method. PMID- 17729231 TI - Complete (1)H NMR spectral fingerprint of huperzine A. AB - Complete analysis of the (1)H NMR spectrum of huperzine A, 1-amino-13-ethylidene 11-methyl-6-aza-tricyclo[7.3.1.0(2, 7)]trideca-2(7),3,10-trien-5-one, a Lycopodium alkaloid and anti-Alzheimer drug lead containing an ABCD(E)(MN)(OP)X(3)Y(3)-type system of 15 nonexchangeable proton spins, is reported for the first time, and earlier assignments are corrected. The complete (1)H parameter set of 11 chemical shifts clarifies the diastereotopism of both methylene groups, and provides a total of 38 observed H,H-couplings including 31 long-range ((4-6)J) connectivities. The NMR data is consistent with the comparatively rigid alicyclic backbone predicted by molecular mechanics calculations, and forms the basis for (1)H NMR fingerprint analysis for the purpose of dereplication, purity analysis, and elucidation of structural analogs. PMID- 17729232 TI - An NMR, IR and theoretical investigation of (1)H chemical shifts and hydrogen bonding in phenols. AB - The change in (1)H NMR chemical shifts upon hydrogen bonding was investigated using both experimental and theoretical methods. The (1)H NMR spectra of a number of phenols were recorded in CDCl(3) and DMSO solvents. For phenol, 2- and 4 cyanophenol and 2-nitrophenol the OH chemical shifts were measured as a function of concentration in CDCl(3). The plots were all linear with concentration, the gradients varying from 0.940 (phenol) to 7.85 (4-cyanophenol) ppm/M because of competing inter- and intramolecular hydrogen bonding. Ab initio calculations of a model acetone/phenol system showed that the OH shielding was linear with the H...O=C distance (R) for R < 2.1 A with a shielding coefficient of - 7.8 ppm/A and proportional to cos(2)phi where phi is the H...O=C--C dihedral angle. Other geometrical parameters had little effect. It was also found that the nuclear shielding profile is unrelated to the hydrogen bonding energy profile. The dependence of the OH chemical shift on the pi density on the oxygen atom was determined as ca 40 ppm/pi electron. This factor is similar to that for NH but four times the value for sp(2) hybridized carbon atoms. The introduction of these effects into the CHARGE programme allowed the calculation of the (1)H chemical shifts of the compounds studied. The CHARGE calculations were compared with those from the ACD database and from GIAO calculations. The CHARGE calculations were more accurate than other calculations both when all the shifts were considered and also when the OH shifts were excluded. The calculations from the ACD and GIAO approaches were reasonable when the OH shifts were excluded but not as good when all the shifts were considered. The poor treatment of the OH shifts in the GIAO calculations is very likely due to the lack of explicit solvent effects in these calculations. PMID- 17729233 TI - 3-Oxo-12alpha-hydroxyfriedelane from Maytenus gonoclada: structure elucidation by (1)H and (13)C chemical shift assignments and 2D-NMR spectroscopy. AB - The compounds 3-oxofriedelane (1), 3beta-hydroxyfriedelane (2), 3,11 dioxofriedelane (3), 3,16-dioxofrie delane (4) and 3-oxo-12alpha hydroxyfriedelane (5) were isolated from the hexane extract of Maytenus gonoclada Mart. (Celastraceae) leaves. Structural formula and the stereochemistry of the new pentacyclic triterpene 3-oxo-12alpha-hydroxyfriedelane (5) were established through (1)H and (13)C NMR and DEPT 135 spectral data including 2D experiments (HMBC, HMQC, COSY, and NOESY) and mass spectrometry (GC-MS). PMID- 17729234 TI - J-modulated ADEQUATE experiments using different kinds of refocusing pulses. AB - Owing to the recent developments concerning residual dipolar couplings (RDCs), the interest in methods for the accurate determination of coupling constants is renascenting. We intended to use the J-modulated ADEQUATE experiment by Kover et al. for the measurement of (13)C - (13)C coupling constants at natural abundance. The use of adiabatic composite chirp pulses instead of the conventional 180 degrees pulses, which compensate for the offset dependence of (13)C 180 degrees pulses, led to irregularities of the line shapes in the indirect dimension causing deviations of the extracted coupling constants. This behaviour was attributed to coupling evolution, during the time of the adiabatic pulse (2 ms), in the J-modulation spin echo. The replacement of this pulse by different kinds of refocusing pulses indicated that a pair of BIPs (broadband inversion pulses), which behave only partially adiabatic, leads to correct line shapes and coupling constants conserving the good sensitivity obtained with adiabatic pulses. PMID- 17729237 TI - A potent replicative delta-24 adenoviral vector driven by the promoter of human papillomavirus 16 that is highly selective for associated neoplasms. AB - BACKGROUND: Several human epithelial neoplasms are associated with high-risk strains of human papillomavirus (HPV) such as cervical, anorectal, and other carcinomas. For some tumor types the current therapeutic tools are only palliative. Conditionally replicative adenoviruses (CRAds) are promising antineoplastic agents, which also can trigger confined antitumor effects. METHODS: We constructed a series of CRAds driven by the upstream regulatory promoter region (URR) of an Asian-American variant of HPV-16, which contained different mutations at the E1A region (dl1015 and/or Delta24) and wild-type. All vectors were tested in vitro for viral replication and cytotoxicity. Viral DNA replication and E1A expression were also assessed by quantitative PCR. Finally, we confirmed the antitumoral efficacy of this vector in injected and non-injected xenotransplanted cervical tumors in a murine model for tumor regression and survival studies. RESULTS: A vector denominated Ad-URR/E1ADelta24 displayed a potent cytopathic effect associated with high selectivity for HPV+ cell lines. We found that the oncolytic effect of this CRAd was comparable to Ad-wt or Ad Delta24, but this efficacy was significantly attenuated in HPV- cell lines, an effect that was contributed by the URR promoter. Ad-URR/E1ADelta24 was very effective to control tumor growth, in both, injected and non-injected tumors generated with two different HPV+ cell lines. CONCLUSIONS: CRAd Ad-URR/E1ADelta24 is a highly selective vector for HPV+ cell lines and tumors that preserves the oncolytic efficacy of Ad-wt and Ad-Delta24. Our preclinical data suggest that this vector may be useful and safe for the treatment of tumors induced by HPV, like cervical cancers. PMID- 17729238 TI - Complete assignments of (1)H and (13)C NMR spectral data for arylnaphthalene lignan lactones. AB - In this work we describe the complete (1)H and (13)C NMR analyses of three arylnaphtalene lignan lactones (taiwanin C, 4-methyl dehydroretrodendrin and justicidin B) using modern NMR techniques such as gCOSY, nonedited gHSQC, gHMBC and NOE experiments. Complete assignment and homonuclear hydrogen coupling constant measurements were performed. PMID- 17729239 TI - Vaccines to treat cancer--an old approach whose time has arrived. AB - There are extensive DNA changes in tumor cells and the genes of tumor cells continuously mutate at a high rate. While this can provide therapeutic targets, it makes it unlikely that an agent that is selective for a single target will work against all cells in a tumor. However, it may be possible to use tumor epitopes as sentinels to engage adaptive and innate immunological mechanisms and create a tumor destructive environment effective also against variant cells that have lost a given antigen or their ability to present it. We hypothesize that therapeutic tumor vaccines, in combination with the targeting, to tumors, of costimulatory molecules such as anti-CD137scFv, or lymphokines such as GMCSF, will expand anti-tumor responses for therapeutic benefit when used as an adjunct to surgery and chemotherapy. PMID- 17729240 TI - Ecological network analysis: an application to the evaluation of effects of pesticide use in an agricultural environment. AB - Ecological network analysis is used to evaluate the impact of pesticide use on ecological systems in the context of agricultural farmland environments. The aim is to provide support for the design of effective and minimally damaging pest control strategies. The ecological network analysis can identify species that are important to the integrity of the ecological network. The methodology can be used to monitor the impact of shifts in terms of types of pesticide used on the ecological system. The authors' intention is to use this methodology to provide supporting evidence for the UK Voluntary Initiative programme aimed at convincing farmers voluntarily to make improved choices in the use of a wide range of pesticides. PMID- 17729241 TI - Role of prothrombin complex concentrates in reversing warfarin anticoagulation: a review of the literature. AB - Over-anticoagulation is a common problem with warfarin therapy and can lead to major or life-threatening bleeding. The goal of urgent warfarin reversal is to elevate or replace vitamin K-dependent clotting factors. In the United States, fresh frozen plasma (FFP) is considered the standard of care for warfarin reversal. Prothrombin complex concentrates (PCCs) offer an alternative to FFP for rapidly replacing deficient clotting factors and correcting the international normalized ratio (INR). However, few prospective clinical trials have been conducted to evaluate the effectiveness of these concentrates relative to other treatment modalities. A review of the published literature over the last 30 years found that PCCs offer a rapid and specific method for replacing vitamin K dependent clotting factors and restoring normal hemostasis in the context of over coagulation. In those studies in which PCCs were compared with FFP, PCCs were found more effective in shortening the time to INR correction and were associated with a low risk of thrombotic adverse events. Evidence-based treatment guidelines are needed to optimize the use of PCCs for warfarin reversal. PMID- 17729242 TI - Too many hits in HIT? PMID- 17729243 TI - Baseline mannose binding lectin levels may not predict infection among children with leukemia. AB - We measured baseline serum mannose binding lectin (MBL) levels in 91 patients with childhood leukemia to determine their predictive value for the development of febrile neutropenia or specific infections. Median MBL levels did not differ significantly between patients who developed febrile neutropenia, bacterial infection, or disseminated fungal infection and those who did not. In addition, low MBL levels were not associated with an increased cumulative incidence of infection or with a shorter time to first infection. This preliminary study suggests that baseline MBL levels may not be clinically useful to identify pediatric leukemia patients who are at increased risk of infection. Additional studies are required to determine whether serial MBL measurements may be valuable for this purpose. PMID- 17729246 TI - Impact of reactivation on the sequelae of multi-system Langerhans cell histiocytosis patients. PMID- 17729245 TI - Treatment of wild-type gastrointestinal stromal tumor (WT-GIST) with imatinib and sunitinib. AB - We report a rare case of advanced, metastatic gastrointestinal stromal tumor (GIST) in a young female. Molecular analysis of the tumor revealed wild-type (WT) KIT and platelet derived growth factor receptor alpha (PDGFRA) gene status with no mutations characteristic of adult GIST. Despite this she had clinical benefit and evidence of radiological response to sequential treatment with the tyrosine kinase inhibitors imatinib and sunitinib. PMID- 17729247 TI - Timing of menarche among survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. AB - BACKGROUND: The objective of this study was to determine risk factors associated with abnormal timing of menarche among survivors of childhood acute lymphoblastic leukemia (ALL). PROCEDURE: Self-reported age of menarche was determined among 949 female ALL survivors participating in the Childhood Cancer Survivor Study (CCSS), a cohort of 5-year survivors of common pediatric cancers diagnosed from 1970 to 1986, and compared with 1,128 siblings. RESULTS: The majority of survivors (92%) and siblings (97%) reported menarche between the ages of 10 and 16. Survivors treated with chemotherapy alone, including those exposed to alkylating agents, experienced menarche at a similar rate to siblings. However, compared to chemotherapy alone, cranial radiotherapy was associated with early menarche (age < 10; OR 6.2, 95% CI 2.1, 18.5) while craniospinal radiotherapy was associated with both early (OR 8.6, 95% CI 1.9, 38.6) and late (age > 16; OR 4.8, 95% CI 1.4, 16.7) menarche. There were no differences in effect between <20 and >/=20 Gy radiotherapy doses. In multivariable analysis, younger age at diagnosis was an independent risk factor for early menarche. CONCLUSIONS: Few female childhood ALL survivors experienced menarche outside of the normal range. Alkylating agent exposure was not associated with abnormal timing. However, those exposed to cranial and craniospinal radiotherapy, especially at a young age, should be monitored closely for abnormal timing of menarche. PMID- 17729248 TI - Re: Loss of antibody titers and effectiveness of revaccination in post chemotherapy pediatric sarcoma patients. PMID- 17729249 TI - Outcomes of a two-drug chemotherapy regimen for intraocular retinoblastoma. AB - BACKGROUND: Retinoblastoma is the most common intraocular tumor of childhood. Vision salvage rates in advanced cases are less than ideal, and the optimal treatment for intraocular retinoblastoma has not been established. We report the results of an institutional retinoblastoma treatment trial to determine the vision salvage rates and toxicity of a regimen combining carboplatin and etoposide with focal retinal therapy. PROCEDURE: Twenty-nine patients diagnosed with retinoblastoma in 48 eyes were treated between 1992 and 2004 with at least six cycles of carboplatin and etoposide combined with focal retinal therapy. RESULTS: The response rate of eyes after six cycles of chemotherapy was 85.4%. Twenty-two eyes were enucleated, but only seven eyes received EBRT. The vision salvage rate without EBRT was 82.6% for eyes with Reese-Ellsworth (R-E) groups I IV tumors and 20% for eyes with R-E group V tumors. The vision salvage rate without EBRT for eyes with Murphree groups A and B tumors was 77.3% but was only 26.9% for eyes with groups C and D tumors. Acute side effects were minimal. CONCLUSIONS: The combination of carboplatin and etoposide with focal therapy is a well-tolerated regimen that has acceptable vision salvage rates for R-E groups I IV and Murphree groups A and B retinoblastoma. This combination avoids the use of EBRT and the toxicity of additional chemotherapy agents. However, patients with R E group V and Murphree groups C and D retinoblastoma have poorer outcomes and require more intensive therapy. PMID- 17729250 TI - Prevention and management of central venous catheter occlusion and thrombosis in children with cancer. AB - BACKGROUND: The views and clinical practice of children's cancer units were surveyed regarding management of central venous catheter (CVC) occlusion (CVC occlusion), CVC-related thrombosis (CVC-thrombosis) and thromboembolism (CVC thromboembolism). PROCEDURE: A questionnaire was sent to all 22 United Kingdom Children's Cancer Study Group centres, requesting information about their views of the importance of, and their practices regarding, prophylaxis, diagnosis and treatment of CVC-occlusion/thrombosis. RESULTS: Twenty (91%) centres responded. Eighty percent, 80% and 70%, respectively, stated that CVC-occlusion, CVC thrombosis and CVC-thromboembolism were clinically important concerns. All centres used heparinised saline flushes as prophylaxis against CVC-occlusion, with little variation ( GFR > or = 20 mL x minute(-1)), moderate renal impairment (20 > GFR > or = 10 mL x minute(-1)), and severe renal impairment (GFR < 10 mL x minute(-1)). The renal ADCs between four groups were statistically compared by analysis of variance (ANOVA), and the relationship between ADCs and GFR was examined using Pearson's correlation test. RESULTS: The mean renal ADCs of the four groups were 2.87 +/- 0.11, 2.55 +/- 0.17, 2.29 +/- 0.10, and 2.20 +/- 0.11 x 10(-3)mm(2)/second, respectively. There was a statistically significant difference in renal ADCs among the four groups (P < 0.001). There was a positive correlation between the ADCs and split GFR (r = 0.709). CONCLUSION: The ADCs were significantly lower in impaired kidneys than in normal kidneys, and there was a positive correlation between the ADCs and GFR. PMID- 17729336 TI - Thigh muscle stiffness assessed with magnetic resonance elastography in hyperthyroid patients before and after medical treatment. AB - PURPOSE: To measure the stiffness of the vastus medialis (VM) in hyperthyroid patients before and after treatment. MATERIALS AND METHODS: A total of five healthy euthyroid patients and five hyperthyroid patients were tested using magnetic resonance elastography (MRE), which involves the induction of shear waves in the thigh muscles using a pneumatic driver at 90 Hz. RESULTS: Among the pretreatment hyperthyroid cohort a lower stiffness was found when the muscle was relaxed (2.11 +/- 0.61 kPa) compared the stiffness following treatment of hyperthyroidism (5.52 +/- 1.52 kPa), which was accompanied by an improvement in the contractile function of the VM. Pretreatment muscle stiffness was also less than that of age matched healthy volunteers (4.56 +/- 0.40 kPa). The behavior of the waves was sensitive to the stage of this myopathy and to the amount of free thyroxine (FT4). CONCLUSION: The MRE technique provides a new tool to gain new insights into pathophysiology of thyroid associated and other muscle diseases and their response to treatment. PMID- 17729337 TI - Oblique MR imaging of the anterior cruciate ligament based on three-dimensional orientation. AB - PURPOSE: To investigate the three-dimensional (3D) course of the anterior cruciate ligament (ACL) and determine the optimum planes for oblique full-length MRI of the ligament. MATERIALS AND METHODS: Twenty-five healthy volunteers were examined. Axial proton density-weighted (PDw) images of the knees of 20 volunteers were obtained. 3D paths along the course of the ACL and corresponding tangents were constructed. Angles between these tangents and reference lines RFL 1 (the line connecting the posterior edges of the femoral condyles), RFL-2 (the line through the intercondylar joint space), and RFL-3 (the line connecting the anterior and posterior edge of the medial tibial condyle) were measured. These angles were used for oblique T2-weighted (T2w) MRI of the knees of the remaining five volunteers, and the number of slices that depicted the entire ACL was calculated. RESULTS: The mean angles to the ACL were 74.0 degrees for RFL-1, 79.9 degrees for RFL-2, and 70.4 degrees for RFL-3. Full-length visualization of the ACL was demonstrated by 1.4 slices using the sagittal oblique plane prescribed for RFL-1, 2.4 slices using the sagittal oblique plane prescribed for RFL-2, and 1.4 slices using the coronal oblique plane prescribed for RFL-3. CONCLUSION: The ACL is best depicted using a sagittal oblique imaging plane angled at 80 degrees from a line through the intercondylar joint space. PMID- 17729341 TI - Whole-body MR imaging vs. FDG-PET: comparison of accuracy of M-stage diagnosis for lung cancer patients. AB - PURPOSE: To conduct a prospective comparison of the accuracy of whole-body MR imaging and positron emission tomography (PET) with fluorine-18 deoxyglucose (FDG) (FDG-PET) to assess the M-stage in lung cancer patients. MATERIALS AND METHODS: A total of 90 consecutive lung cancer patients (mean age = 68 years) underwent whole-body MR imaging and FDG-PET as well as other standard radiological imaging procedures before and after treatment. Probabilities of metastases on whole-body MR imaging and FDG-PET were assessed by using 5-point scoring systems on a per-site basis and on a per-patient basis. Receiver operating characteristic (ROC) curve analysis was used to compare diagnostic capabilities. Sensitivity, specificity, and accuracy were also compared by using the McNemar's test on a per-site and per-patient basis. RESULTS: For assessment of head and neck metastases and bone metastases, accuracies of whole-body MR imaging (95.0% and 94.8%, respectively) were significantly higher than those of FDG-PET (89.1% and 88.2%, respectively; P < 0.05). For assessment of the M-stage on a per-patient basis, accuracy of whole-body MR imaging (80.0%) was also significantly higher than that of FDG-PET (73.3%; P < 0.05). CONCLUSION: Whole body MR imaging is an accurate diagnostic technique and may be considered at least as effective as FDG-PET for assessment of the M-stage of lung cancer patients. PMID- 17729342 TI - T(1) and T(2) measurements of the fine structures of the in vivo and enucleated human eye. AB - PURPOSE: To measure T(1) and T(2) of the fine structures of the in vivo eye. MATERIALS AND METHODS: Involuntary saccades make it difficult to obtain artifact free images. Using a method recently reported (Bert et al, Acad Radiol 2006;12:368-378), near artifact-free spin-echo images were obtained. Both an isolated enucleated eye and eight human subjects were studied at 1.5 T. Spin-echo variable TR/TE data was acquired for T(1)/T(2) determination. Average relaxation times were calculated two ways. First, an arithmetic average over different subjects was computed. Second, all data was normalized using the fitted amplitudes of each data set and pooled to obtain a single least squares fit. RESULTS: In vivo T(1)/T(2) (msec) are: arithmetic average T(1), T(2), normalized data T(1), T(2). Anterior chamber: 6233 +/- 979, 468 +/- 149, 5053 +/- 1052, 450 +/- 49. Ciliary body: 1916 +/- 184, 80 +/- 7, 2038 +/- 114, 76 +/- 3. Chorioretina: 1717 +/- 500, 72 +/- 25, 1511 +/- 230, 78 +/- 3. Extraocular muscle: 1581 +/- 646, 41 +/- 7, 1470 +/- 231, 41 +/- 1. Iris: 3334 +/- 989, 163 +/- 63, 3376 +/- 338, 153 +/- 10. Lens cortex: 1712 +/- 466, 93 +/- 36, 1413 +/- 177, 100 +/- 5. Lens nucleus: 1133 +/- 40, 26 +/- 3, 1138 +/- 47, 25 +/- 0.4. Optic nerve: 1906 +/- 301, 68 +/- 16, 1805 +/- 244, 71 +/- 2. Posterior chamber: 7915 +/- 4897, 241 +/- 14, 3323 +/- 2154, 251 +/- 38. Vitreous humor: 5768 +/- 1190, 756 +/- 804, 4855 +/- 1846, 390 +/- 8. CONCLUSION: In vivo T(1) and T(2) for many of the fine structures of the human eye have been measured. PMID- 17729339 TI - Effects of signal-to-noise ratio on the accuracy and reproducibility of diffusion tensor imaging-derived fractional anisotropy, mean diffusivity, and principal eigenvector measurements at 1.5 T. AB - PURPOSE: To develop an experimental protocol to calculate the precision and accuracy of fractional anisotropy (FA), mean diffusivity (MD), and the orientation of the principal eigenvector (PEV) as a function of the signal-to noise ratio (SNR) in vivo. MATERIALS AND METHODS: A healthy male volunteer was scanned in three separate scanning sessions, yielding a total of 45 diffusion tensor imaging (DTI) scans. To provide FA, MD, and PEV as a function of SNR, sequential scans from a scan session were grouped into nonintersecting sets. Analysis of the accuracy and precision of the DTI-derived contrasts was done in both a voxel-wise and region of interest (ROI)-based manner. RESULTS: An upward bias of FA and no significant bias in MD were present as SNR decreased, confirming results from simulation-based studies. Notably, while the precision of the PEV became worse at low SNR, no bias in the PEV orientation was observed. Overall, an accurate and precise quantification of FA values in GM requires substantially more SNR than the quantification of white matter (WM) FA values CONCLUSION: This study provides guidance for FA, MD, and PEV quantification and a means to investigate the minimal detectable differences within and across scan sessions as a function of SNR. PMID- 17729343 TI - Magnetic resonance imaging of vulnerable atherosclerotic plaques: current imaging strategies and molecular imaging probes. AB - The vulnerability or destabilization of atherosclerotic plaques has been directly linked to plaque composition. Imaging modalities, such as magnetic resonance (MR) imaging, that allow for evaluation of plaque composition at a cellular and molecular level, could further improve the detection of vulnerable plaque and may allow for monitoring the efficacy of antiatherosclerotic therapies. In this review we focus on MR imaging strategies for the detection and evaluation of atherosclerotic plaques and their composition. We highlight recent advancements in the development of MR pulse sequences, computer image analysis, and the use of commercially available MR contrast agents, such as gadopentic acid (Gd-DTPA), for plaque characterization. We also discuss molecular imaging strategies that are currently being used to design specific imaging probes targeted to biochemical and cellular markers of atherosclerotic plaque vulnerability. PMID- 17729344 TI - Brain diffusivity in patients with neuropsychiatric systemic lupus erythematosus with new acute neurological symptoms. AB - PURPOSE: To investigate the source of significant difference in apparent diffusion coefficient (ADC) between patients with acute symptoms of neuropsychiatric (NP) systematic lupus erythematosus (SLE) (NPSLE) and normal controls. MATERIALS AND METHODS: Diffusion-weighted echo-planar imaging was performed on 1.5-T scanners in 17 female and four male NPSLE patients with acute neurological symptoms (23-76 years, mean = 42.7 years), and in 21 aged-matched healthy controls (16 female, five male, 26-63 years, mean = 41.1 years). ADC histograms were calculated for whole brain, gray matter tissue, and white matter tissue. RESULTS: Of the 17 NPSLE patients, 13 (72%) had abnormal findings on MR imaging. The NPSLE patients had a mean ADC value of (1105.1 +/- 23.6) x 10(-6) mm(2)/second and the control had a mean ADC value of (1012.5 +/- 9.4) x 10(-6) mm(2)/second (P < or = 0.0012). Significant differences were also found in white matter (P < or = 0.0020) and gray matter (P < or = 0.0022). CONCLUSION: ADC histogram analysis demonstrated increased general diffusivity in the brain in NPSLE patients with acute symptoms compared with healthy normal controls. This finding suggests that in the brain parenchyma of NPSLE patients a loss of tissue integrity occurs facilitating motility of free-water protons. PMID- 17729345 TI - Myocardial tissue characterization and the role of chronic anemia in sickle cell cardiomyopathy. AB - PURPOSE: To use cardiovascular magnetic resonance (CMR) techniques to examine possible causes for the left ventricular (LV) dilatation that occurs in sickle cell disease (SCD), including the effects of chronic anemia, iron-induced cardiomyopathy, and regional fibrosis due to sludge infarcts that occur during sickle crises. MATERIALS AND METHODS: A total of 47 patients with sickle cell anemia were assessed for LV function and myocardial iron levels using CMR measurements; 30 of these were also assessed for regional fibrosis using late gadolinium-enhancement CMR. The LV function was compared to both normal controls and transfusion dependent non-iron-loaded (NIL) thalassemia major (TM) patients. RESULTS: Only one SCD patient had significant myocardial iron loading, and only two patients had regional fibrosis. There were significant differences in ventricular volumes of the sickle patients compared with both the normal controls and the NIL-TM population (P < 0.01). CONCLUSION: The LV changes seen in SCD are partly the result of a chronic anemia but there appears to be another contributory factor. This extra factor is not myocardial iron loading or regional fibrosis, although a homogenous fibrotic disorder affecting the left ventricle cannot be excluded. PMID- 17729346 TI - Two-dimensional fast imaging employing steady-state acquisition (FIESTA) cine acquisition of fetal non-central nervous system abnormalities. AB - PURPOSE: To evaluate the value of two-dimensional fast imaging employing steady state acquisition (2D FIESTA) cine MR with parallel imaging techniques in the diagnosis of fetal non-central nervous system (CNS) anomalies. MATERIALS AND METHODS: A total of 28 pregnant women were referred for further MR evaluation on fetuses after abnormal sonographic results. A total of 33 fetal MR examinations were performed by a 1.5 T MR scanner with eight-channel phase-arrayed body coils. Single-shot fast spin-echo (SSFSE(R), GE) of three orthogonal planes and 2D FIESTA for cine fetal MR of three sagittal planes (midsagittal and 10 mm off midline on left and right) were routinely acquired. Additional planes on target organs with variable imaging frames were added if indicated. RESULTS: Nine of the 33 examinations (9/33; 27.3%) had motion artifacts obscuring the detail in SSFSE imaging; 2D FIESTA imaging provided motion-artifact-free imaging in all of them. Cine 2D FIESTA imaging provided additional information on the visceral peristalsis. The information helped in differentiating dilated gastrointestinal (GI) tract from other intraabdominal cystic lesions and in confirming the nature and level of GI tract obstruction. CONCLUSION: With sub-half-second temporal resolution of the 2D FIESTA sequences, fetal movement is no longer problematic. In addition to the anatomical information also provided by conventional SSFSE sequences, 2D FIESTA demonstrates information on motility and peristalsis of hollow organs and helps the diagnosis of fetal visceral anomalies. PMID- 17729347 TI - Physiological changes of the human uterine myometrium during menstrual cycle: preliminary evaluation using BOLD MR imaging. AB - PURPOSE: To investigate the T2* values within the junctional zone and outer uterine myometrium and their changes during the menstrual cycle, and thus to evaluate their physiologic changes on blood oxygenation level-dependent (BOLD) magnetic resonance (MR) imaging. MATERIALS AND METHODS: Single-shot echo-planar imaging (EPI) was used to acquire T2*-weighted images (TR/TE = 1000 msec/23-150 msec) from 15 healthy females with a 1.5-T magnet. T2* values of both junctional zone and outer uterine myometrium were measured within a single breathhold and during three menstrual cycle phases (menstrual, periovulatory, and luteal phase). Signal intensities of uterine myometrium on T2-weighted images were also evaluated. RESULTS: T2* could successfully be calculated in 13 subjects. T2* values for the junctional zone were significantly lower than those of the outer myometrium at every phase(P < 0.001), and T2* values of both junctional zone (P < 0.05) and outer (P < 0.01). Myometrium in the menstrual phase was significantly lower than those in the other phases. On T2-weighted images, the signal intensity of the junctional zone was significantly lower than outer myometrium in every phase (P < 0.01), but there was no significant difference among menstrual cycle phases in both layers (P > 0.05). CONCLUSION: This preliminary study suggested that menstrual cycle changes of the uterine myometrium were shown by BOLD imaging. BOLD MR imaging may be an potential modality to investigate physiologic changes of the uterine myometrium during the menstrual cycle. PMID- 17729348 TI - Application of voxelwise analysis in the detection of regions of reduced fractional anisotropy in multiple sclerosis patients. AB - PURPOSE: To investigate the utility of voxelwise analysis in the detection of lesions in the normal appearing white matter (NAWM) of individual multiple sclerosis (MS) patients. MATERIALS AND METHODS: Diffusion tensor imaging (DTI) was performed on 10 normal controls and six patients with MS lesions. The fractional anisotropy (FA) maps derived from the diffusion-weighted images were then spatially normalized (via an affine transformation) into Montreal Neurological Institute (MNI) space, and the normalized FA map of each of the patients was compared voxelwise with the normalized FA maps of the group of normals in a one-sample t-test (P = 0.0001). Two independent board-certified neuroradiologists reviewed the data. RESULTS: In the patient data for all six cases, the two reviewers determined detection sensitivities of 72% and 96% for the voxelwise technique based on known fluid-attenuated inversion-recovery (FLAIR) lesions. In addition, between the two reviewers, nine NAWM regions exhibiting FA reductions were identified in the six patients. However, numerous regions of abnormal FA were detected that were attributed to poor intersubject image registration. CONCLUSION: Voxelwise analysis of spatially normalized FA maps has the potential to identify regions of FA reduction in lesions and in the NAWM of individual MS patients in a rapid and reproducible fashion. J. Magn. Reson. Imaging 2007;26:552-556. (c) 2007 Wiley-Liss, Inc. PMID- 17729349 TI - Confounding effects of volatile anesthesia on CBV assessment in rodent forebrain following ethanol challenge. AB - PURPOSE: To compare and contrast the pattern and characteristics of the cerebral blood volume (CBV) response to ethanol (EtOH) in rats under awake and anesthetized conditions. MATERIALS AND METHODS: Acute EtOH (0.75 g/kg) challenge induced CBV changes were measured using a contrast-enhanced functional MRI CBV method in 15 male Sprague Dawley rats under three experimental conditions: 1.0% to 1.2% isoflurane (N = 5); 0.8% halothane (N = 5); and awake with no anesthetic (N = 5). Physiological parameters were collected from bench settings in nine rats from the above different conditions. Four parameters: 1) area under the curve (AUC%); 2) the maximum signal change (Max%); 3) EtOH absorption rate (alpha(2)); and 4) EtOH elimination rate (alpha(1)) were employed to compare EtOH-induced MRI signals between the awake and anesthetized groups. RESULTS: Both awake and anesthetized animals responded with an increase in CBV to EtOH challenge. However, the presence of anesthesia promoted a significant preferential flow to subcortical areas not seen in the awake condition. CONCLUSION: Unclear mechanisms of anesthesia add a layer of uncertainty to the already complex interpretation of EtOH's influence on neuronal activity, cellular metabolism, and hemodynamic coupling. PMID- 17729350 TI - Non-model-based correction of respiratory motion using beat-to-beat 3D spiral fat selective imaging. AB - PURPOSE: To demonstrate the feasibility of retrospective beat-to-beat correction of respiratory motion, without the need for a respiratory motion model. MATERIALS AND METHODS: A high-resolution three-dimensional (3D) spiral black-blood scan of the right coronary artery (RCA) of six healthy volunteers was acquired over 160 cardiac cycles without respiratory gating. One spiral interleaf was acquired per cardiac cycle, prior to each of which a complete low-resolution fat-selective 3D spiral dataset was acquired. The respiratory motion (3D translation) on each cardiac cycle was determined by cross-correlating a region of interest (ROI) in the fat around the artery in the low-resolution datasets with that on a reference end-expiratory dataset. The measured translations were used to correct the raw data of the high-resolution spiral interleaves. RESULTS: Beat-to-beat correction provided consistently good results, with the image quality being better than that obtained with a fixed superior-inferior tracking factor of 0.6 and better than (N = 5) or equal to (N = 1) that achieved using a subject-specific retrospective 3D translation motion model. CONCLUSION: Non-model-based correction of respiratory motion using 3D spiral fat-selective imaging is feasible, and in this small group of volunteers produced better-quality images than a subject-specific retrospective 3D translation motion model. PMID- 17729351 TI - Manganese dipyridoxyl-diphosphate (MnDPDP) as a viability marker in patients with myocardial infarction. AB - PURPOSE: To evaluate contrast accumulation in left ventricular (LV) myocardium after manganese dipyridoxyl-diphosphate (MnDPDP) administration in patients with recent first time myocardial infarction. MATERIALS AND METHODS: MnDPDP (5 micromol/kg) was administered to 10 patients with recent myocardial infarction (three to 12 weeks). One slice of interest (SOI) likely to traverse the infarction was chosen, and sectorial pre- and postcontrast longitudinal relaxivity rates (R(1)) and signal changes during infusion were estimated with a fast gradient echo sequence. LV volume and wall thickening were measured in short axis cine recordings. Infarct localization from R(1) and wall thickening data were compared by vector analyses. RESULTS: Reduced wall thickening was associated with reduced precontrast R(1) and reduced contrast enhancement. Both remote and infarcted regions showed rapid initial contrast accumulation. In remote regions, this was followed by a continuing slow increase. Mean precontrast R(1) was 0.87 +/- 0.06 second(-1) in infarcted regions and 0.96 +/- 0.03 second(-1) in remote regions (P < 0.001). Mean R(1) change over one hour was 0.24 +/- 0.07 second(-1) in infarcted regions and 0.38 +/- 0.03 second(-1) in remote regions (P < 0.0001). CONCLUSION: Remote regions showed larger increases in R(1) than infarcted regions. This is most likely due to selective and slow Mn accumulation in viable myocytes. PMID- 17729352 TI - Numerical simulation of in vitro pulsatile flow and its study using FRISK, a rapid phase contrast technique. AB - PURPOSE: To test the potential of a phase contrast magnetic resonance (PC-MR) sparse sampling technique, fragmented regional interpolation segmentation for k space (FRISK), to capture complex flow features within a breathhold duration by using numerical simulations and experimental approaches. MATERIALS AND METHODS: Computational fluid dynamics (CFD) data of three models were generated: a two chamber orifice flow model simulating valvular regurgitation, a femoral artery model, and a U-shaped model simulating the aortic arch. These data were used to simulate conventional and FRISK PC-MR data acquisitions. FRISK parameters can be adapted for different flow fields to capture either high temporal information or complexly varying spatial information with a temporal component or a mixture of both. In vivo PC-MR images on a healthy volunteer were sampled to compare conventional PC-MR with novel FRISK imaging. RESULTS: In our simulations of three representative models, when only the errors from different sampling sequences were considered, FRISK was shown to maintain or even improve data accuracy while cutting the scan time by at least 50% compared to corresponding conventional PC MR. By adapting the FRISK parameters for flowfields with different features, FRISK was capable of capturing in-plane and through-plane velocity information with excellent detail in approximately 20 heartbeats breathhold duration. The results of the in vivo MR experiment were consistent with the simulation results, showing that breathhold FRISK imaging improved spatial resolution of the data and maintained adequate temporal resolution compared with breathhold conventional imaging. CONCLUSION: FRISK, a new MRI sampling sequence that sparsely samples data and aligns acquired data during postprocessing, provides a scan time advantage of approximately a factor of 2 compared to conventional scans, and allowed rapid or breathhold scanning while obtaining acceptable accuracy. PMID- 17729353 TI - The pyramidal tract has a predictable course through the centrum semiovale: a diffusion-tensor based tractography study. AB - PURPOSE: To identify reproducible anatomical landmarks that would allow predicting the course of the pyramidal tract (PT) through centrum semiovale. MATERIALS AND METHODS: A total of 20 normal volunteers (12 males, eight females) with a mean age of 34 years (range, 20-59 years) were scanned using a 1.5-Tesla clinical MR unit to assess the trajectory of the PT. Neuroanatomical characteristics of the PT passing through the centrum semiovale were assessed by two independent observers. Tractography data of 10 consecutive patients with brain tumor were used to test the precision of anatomy-based prediction of the tract location. RESULTS: On sagittal view, 95% of the PT depicted on tractography displayed a completely straight or primarily straight course through the supratentorial brain. In 98% of tracts, the bending point of the PT was identified < or = 3 mm from the level of the anterior commissure-posterior commissure (AC-PC) plane. In 80% of PT, the intersection with the AC-PC plane occurred midway between the AC and the PC as seen on the sagittal view. Evaluation of the PT in 10 patients with brain tumor revealed that the anatomy based prediction of PT on the contralesional hemisphere was not substantially deviated from the actual tractography depicted PT. PT on the lesional hemispheres, however, had deviations of various degrees. CONCLUSION: The course of the PT through supratentorial brain can be predicted based on easily identifiable landmarks. This anatomy-based prediction can be clinically applied for cases without substantial mass effect from a space occupying lesion. PMID- 17729354 TI - Reproducibility of wall shear stress assessment with the paraboloid method in the internal carotid artery with velocity encoded MRI in healthy young individuals. AB - PURPOSE: To verify whether wall shear stress (WSS) can be assessed in a reproducible manner using automatic model-based segmentation of phase-contrast MR images by determination of flow volume and maximum flow velocity (Vmax) in cross sections of these vessels. MATERIALS AND METHODS: The approach is based on fitting a 3D paraboloid to the actual velocity profiles and on determining Vmax. WSS was measured in the internal carotid arteries of two groups of healthy young volunteers. The reproducibility of rescanning and repositioning was studied in the first group. In the second group a 1-week and a 1-month interval was investigated. Reproducibility was calculated by the intraclass correlation (ICC). RESULTS: The flow volume, Vmax, and WSS averaged over the cardiac cycle were found to be 287.8 +/- 29.7 mL/min, 37.0 +/- 4.6 cm/s, and 1.13 +/- 0.16 Pa, respectively. The diastolic WSS varied between 1.00 +/- 0.21 Pa without averaging to 0.88 +/- 0.16 Pa with temporal and spatial averaging. Systolic WSS was 1.67 +/ 0.33 Pa without averaging and 1.67 +/- 0.25 Pa with averaging. ICC varied between 0.58 and 0.87 without averaging and between 0.75 and 0.90 with averaging for WSS. CONCLUSION: WSS in MR images of the internal carotid artery can be assessed semiautomatically with good to excellent reproducibility without inter- or intraobserver variability using model-based postprocessing. PMID- 17729355 TI - Cepstral estimation of arterial input functions in brain perfusion imaging. AB - PURPOSE: To investigate voxel-specific arterial input functions (AIFs) obtained through blind deconvolution using complex cepstrum liftering. Blindly estimated AIFs have the potential of reducing dispersion effects in perfusion maps and are completely user-independent. MATERIALS AND METHODS: The separability of AIFs and tissue residue functions (TRFs) in the cepstrum domain is exemplified using synthetic data, wherein the AIFs are modeled as gamma variate functions and the TRFs are modeled as exponential or linear functions. A novel separation filter is suggested. Initial results of different blind methods are illustrated using data from a stroke patient. RESULTS: The AIFs and the TRFs partly overlap in the complex cepstrum. The AIFs, obtained using the new separation filter, are closer to those obtained using noncepstral blind separation. CONCLUSION: The overlap of AIFs and TRFs in the complex cepstrum makes reliable separation of the two functions more difficult than previously described. Comparison to noncepstral blind methods suggests that similar optima are found using the new separation filter. PMID- 17729356 TI - Age, gender, and skeletal variation in bone marrow composition: a preliminary study at 3.0 Tesla. AB - PURPOSE: To evaluate the efficacy of MR Spectroscopy (MRS) at 3.0 Tesla for the assessment of normal bone marrow composition and assess the variation in terms of age, gender, and skeletal site. MATERIALS AND METHODS: A total of 16 normal subjects (aged between eight and 57 years) were investigated on a 3.0 Tesla GE Signa system. To investigate axial and peripheral skeleton differences, non-water suppressed spectra were acquired from single voxels in the calcaneus and lumbar spine. In addition, spectra were acquired at multiple vertebral bodies to assess variation within the lumbar spine. Data was also correlated with bone mineral density (BMD) measured in six subjects using dual-energy X-ray absorptiometry (DXA). RESULTS: Fat content was an order of magnitude greater in the heel compared to the spine. An age-related increase was demonstrated in the spine with values greater in men compared to female subjects. Significant trends in vertebral bodies within the same subjects were also shown, with fat content increasing L5 > L1. Population coefficient of variation (CV) was greater for fat fraction (FF) compared to BMD. CONCLUSION: Significant normal variations of marrow composition have been demonstrated, which provide important data for the future interpretation of patient investigations. PMID- 17729357 TI - MR heating tests of MR critical implants. PMID- 17729358 TI - T2-weighted cardiovascular magnetic resonance imaging. AB - Technical advances in T2-weighted cardiovascular MR (CMR) imaging allow for accurate identification and quantification of tissue injuries that alter myocardial T2 relaxation. Of these, myocardial edema is of special relevance. Increased myocardial water content is an important feature of ischemic as well as nonischemic cardiomyopathies, which are often associated with acute myocardial inflammation. In this article, we review technical considerations and discuss clinical indications of myocardial T2-weighted imaging. PMID- 17729359 TI - Evaluation of a resistance-based model for the quantification of pulmonary arterial hypertension using MR flow measurements. AB - PURPOSE: To establish an estimate for the mean pulmonary arterial pressure (mPAP) derived from noninvasive data acquired with magnetic resonance (MR) velocity encoded sequences. MATERIALS AND METHODS: In seven sedated pigs synchronous catheter-based invasive pressure measurements (IPM) and noninvasive MR were acquired in the main pulmonary artery (MPA) at different severities of pulmonary arterial hypertension (PAH) that were caused by infusion of thromboxane A2 (TxA2). The invasively measured mPAP was correlated with the noninvasive MR velocity data and linear combination equations (LCE) were computed. RESULTS: Intravenously applied TxA2 induced a dose dependent level of severity of PAH with an mPAP of up to 54 mmHg without systemic effects. The acceleration time (AT) measured with MR demonstrated the best correlation with the mPAP (r(2) = 0.75). The LCE with the highest correlation (R = 0.945, alpha < 0.01) between IPM and MR revealed a mean difference of 0, a SD of s = 4.66 and a maximal difference of 12.2 mmHg using the Bland-Altman analysis. CONCLUSION: Applying the identified LCE allowed the estimation of the mPAP in an acute and resistance-based model of PAH with high accuracy using noninvasive MR velocity-encoded sequences. PMID- 17729360 TI - Diffusion-weighted MR imaging of uterine endometrial cancer. AB - PURPOSE: To determine the feasibility of diffusion-weighted (DW) MRI of uterine endometrial cancer and to investigate whether the apparent diffusion coefficient (ADC) values of endometrial cancer differ from those of normal endometrium and whether they differ according to the histologic grade of the tumor. MATERIALS AND METHODS: Study population included 18 consecutive females with surgically proven endometrial cancer and 12 females with pathologically confirmed normal endometrium in cervical cancer patients. Visual evaluation and ADC measurement were performed in endometrial cancer and normal endometrium. RESULTS: All endometrial cancer and the normal endometrium appeared hyperintense on DW images. The mean ADC value (10(-3) mm(2)/second) of endometrial cancer was 0.88 +/- 0.16, which was significantly lower (P < 0.01) than that of normal endometrium (1.53 +/ 0.10). The mean ADC value for each histologic grade was 0.93 +/- 0.16 (G1), 0.92 +/- 0.13 (G2), and 0.73 +/- 0.09 (G3). CONCLUSION: The present study showed that DW imaging is feasible in demonstrating uterine endometrial cancer and ADC measurement has a potential ability to differentiate between normal and cancerous tissue of the endometrium. The ADC values of endometrial cancers of higher grade show tendency to decrease compared to those of lower grade, although estimation of histologic grade based on ADC values seems difficult because of considerable overlap. PMID- 17729361 TI - High-resolution MRI of the triangular fibrocartilage complex (TFCC) at 3T: comparison of surface coil and volume coil. AB - PURPOSE: To evaluate high-resolution MRI of the triangular fibrocartilage complex (TFCC) at 3T using a surface coil (SC) or volume coil (VC). MATERIALS AND METHODS: MRI was obtained from nine volunteers in the supine position with a 3 inch SC and in prone position with a transmit-receiver wrist VC at 3 T. Coronal two-dimensional-gradient echo (2D-GRE) images (TR/TE/FA = 500 msec/15 msec/40 degrees , 1 mm slice-thickness, 60 mm field of view [FOV], 192 x 256 matrix) and coronal 3D-GRE images (TR/TE/FA = 33 msec/15 msec/10 degrees , 0.8 mm slice thickness, 80 mm FOV, 256 x 256 matrix) were used. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the TFCC and surrounding structures were measured. For qualitative measurement, visualization of TFCC and intercarpal ligaments was graded. RESULTS: SNR of TFCC, cartilage, and bone marrow on 2D-GRE with SC/VC was as follows: 5.3/5.3 (TFCC), 16.5/14.4 (cartilage), and 3.61/3.96 (bone marrow). 3D-GRE showed similar SNR. Cartilage-TFCC/cartilage-bone marrow CNR were 11.1/12.8 (SC-2D-GRE), 8.8/10.5 (VC-2D-GRE), 14.1/15.5 (SC-3D-GRE), and 11.9/15.0 (VC-3D-GRE). Quantitative values were not significantly different between SC and VC. Visualization of TFCC and intercarpal ligament with SC was superior to that with VC. All structures show higher scores with 3D-GRE imaging compared to 2D-GRE imaging. CONCLUSION: SC may provide superior qualitative and quantitative results and can be an alternative in case of difficulty in prone position at 3T. PMID- 17729363 TI - Transperineal prostate biopsy under magnetic resonance image guidance: a needle placement accuracy study. AB - PURPOSE: To quantify needle placement accuracy of magnetic resonance image (MRI) guided core needle biopsy of the prostate. MATERIALS AND METHODS: A total of 10 biopsies were performed with 18-gauge (G) core biopsy needle via a percutaneous transperineal approach. Needle placement error was assessed by comparing the coordinates of preplanned targets with the needle tip measured from the intraprocedural coherent gradient echo images. The source of these errors was subsequently investigated by measuring displacement caused by needle deflection and needle susceptibility artifact shift in controlled phantom studies. Needle placement error due to misalignment of the needle template guide was also evaluated. RESULTS: The mean and standard deviation (SD) of errors in targeted biopsies was 6.5 +/- 3.5 mm. Phantom experiments showed significant placement error due to needle deflection with a needle with an asymmetrically beveled tip (3.2-8.7 mm depending on tissue type) but significantly smaller error with a symmetrical bevel (0.6-1.1 mm). Needle susceptibility artifacts observed a shift of 1.6 +/- 0.4 mm from the true needle axis. Misalignment of the needle template guide contributed an error of 1.5 +/- 0.3 mm. CONCLUSION: Needle placement error was clinically significant in MRI-guided biopsy for diagnosis of prostate cancer. Needle placement error due to needle deflection was the most significant cause of error, especially for needles with an asymmetrical bevel. PMID- 17729364 TI - Maximizing contrast-to-noise ratio in ultra-high resolution peripheral MR angiography using a blood pool agent and parallel imaging. AB - PURPOSE: To determine sequence parameters that maximize vascular contrast-to noise (CNR) for ultra-high resolution equilibrium phase (EP) peripheral imaging for the blood pool agent (BPA) Vasovist. MATERIALS AND METHODS: A model for maximizing CNR in EP MR angiography (MRA) is presented. Tissue relaxation times, coil geometry (g)-factors, and clinical imaging requirements (voxel volume and scan time) were determined from human studies. Using these known values, parameters for TR, TE, bandwidth, flip angle (FA), and sensitivity encoding (SENSE) factor that maximized CNR were derived from the model. CNR was enhanced by using reduction in scan time gained from parallel imaging to increase TR and minimize bandwidth. A total of 10 patients were imaged using model-derived EP CE MRA parameters. RESULTS: The model closely predicted experimental CNR data measured in two clinical studies (r(2) = 0.85) and demonstrated an increase in CNR by a factor of 2.3 when subjects were imaged using optimal sequence parameters (P < 0.001). Thigh and calf data were acquired with voxel volumes on the order of 0.2 mm(3) using a SENSE factor of 4. CONCLUSION: Recommended imaging parameters for a 12-channel and 18-channel peripheral vascular coil at two doses of Vasovist (0.03 mmol/kg and 0.05 mmol/kg) are presented. PMID- 17729365 TI - Dynamic T(1) mapping predicts outcome of chemoradiation therapy in primary rectal carcinoma: sequence implementation and data analysis. AB - PURPOSE: To describe details about the implementation of a dynamic T(1)-mapping technique and a simple data analysis strategy that can be used to predict therapy outcome in primary rectal carcinoma and to investigate the physiologic meaning of the obtained parameter. MATERIALS AND METHODS: Contrast-enhanced dynamic T(1) mapping was achieved with a snapshot fast low-angle shot (FLASH) T(1) mapping sequence implemented on a 1.5 T MR scanner. This method was applied to 58 patients with primary rectal cancer before onset of chemoradiation therapy. A simple data analysis strategy based on the calculation of the maximum slope of the tissue concentration-time curve divided by the maximum of the arterial input function (AIF) was used as a measure of tumor microcirculation (PI values). RESULTS: The snapshot FLASH (SFL) T(1)-mapping technique is accurate and sensitive enough to detect inhomogeneous uptake kinetics within tumor tissue. Classifying the patients into two groups according to therapy response showed lower mean PI values for responders as compared to nonresponders. PI was found to combine information about permeability surface area product (PS) and blood volume. CONCLUSIONS: The described method based on dynamic T(1) mapping has the potential to be a clinical tool for predicting therapy outcome of preoperative chemoradiation in patients with primary rectal carcinoma. PMID- 17729366 TI - Improved bulk myocardial motion suppression for navigator-gated coronary magnetic resonance imaging. AB - PURPOSE: To evaluate the impact of a new, cross-correlation based method for compensation of respiratory induced motion of the heart using an individually adapted three-dimensional (3D) translation or affine transformation approach. MATERIALS AND METHODS: A total of 32 patients underwent a routine cardiac MR examination. In each patient, a calibration scan was performed during free breathing to register breathing-related motion within a 3D ellipsoid registration kernel covering the entire heart. Three navigators were employed for all three spatial dimensions (feet-head, anterior-posterior, and left-right) and the optimal translatory correction factors for each spatial dimension were determined. In addition, the cross-correlations for different motion models (no compensation, fixed 1D-translation, adapted 3D-translation, and affine transformation) were calculated. RESULTS: The mean correction factor for the feet head direction was 0.45 +/- 0.13. Though the mean correction factors for the anterior-posterior and left-right direction were nearly zero (-0.01 +/- 0.08 and 0.02 +/- 0.09, respectively), the correction factors exceeded the amount of 0.1 in 12 (19%) and in 19 patients (30%), respectively. All motion compensation models showed significantly higher cross-correlations when compared to "no compensation" (P < 0.05). In particular, the affine transformation algorithm achieved the highest cross-correlation values (88.3 +/- 5.1%) with a significant increase compared to fixed 1D translation (84.7 +/- 6.5%, P < 0.05). CONCLUSION: A considerable number of patients demonstrated relevant breathing-related movement of the heart in the anterior-posterior or left-right direction in addition to the predominant breathing-related movement in the feet-head direction. Thus, it is recommended to compensate for all three spatial dimensions. The affine transformation algorithm combined with three navigators significantly improved breathing-related cardiac motion compensation when compared to the conventionally applied 1D translation with a fixed correction factor. PMID- 17729367 TI - Automated analysis of contrast enhancement in breast MRI lesions using mean shift clustering for ROI selection. AB - PURPOSE: To evaluate a new method for automated determination of a region of interest (ROI) for the analysis of contrast enhancement in breast MRI. MATERIALS AND METHODS: Mean shift multidimensional clustering (MS-MDC) was employed to divide 92 lesions into several spatially contiguous clusters each, based on multiple enhancement parameters. The ROIs were defined as the clusters with the highest probability of malignancy. The performance of enhancement analysis within these ROIs was estimated using the area under the receiver operator characteristic curve (AUC), and compared against a radiologist's final assessment and a classifier using histogram analysis (HA). For HA, the first, second, and third quartiles were evaluated. RESULTS: MS-MDC resulted in AUC = 0.88 with a 95% confidence interval (CI) of 0.81-0.95. The AUC for the radiologist's assessment was 0.93 (95%CI = 0.87-0.97). Best HA performance was found using the first quartile, with AUC = 0.79 (95%CI = 0.69-0.88). There was no significant difference between MS-MDC and the radiologist (P = 0.40). The improvement of MS MDC over HA was significant (P = 0.018). CONCLUSION: Mean shift clustering followed by automated selection of the most suspicious cluster resulted in accurate ROIs in breast MRI lesions. PMID- 17729368 TI - Study of ulnar variance with high-resolution MRI: correlation with triangular fibrocartilage complex and cartilage of ulnar side of wrist. AB - PURPOSE: To investigate correlations with ulnar variance and the triangular fibrocartilage complex (TFCC) or cartilage of ulnar side of the wrist on high resolution MRI with a microscopy coil. MATERIALS AND METHODS: We reviewed ulnar variance, TFCC, and cartilage of the ulnar side of the wrist in 93 subjects (29 asymptomatic volunteers and 64 patients with suspected TFCC injury) with high resolution MRI using a 47-mm microscopy surface coil. All MR images were obtained with a 1.5 T scanner. Coronal 2D gradient recalled echo T(2)*-weighted images were used for analysis. For qualitative analysis we measured ulnar variance, TFCC angle, thickness in the central portion of TFCC disc proper, and cartilage thickness of the lunate and the ulnar head on MRI and calculated the correlation coefficient between measured values. We also examined the relationship between ulnar variance and age or sex. RESULTS: High-resolution MR images clearly demonstrated TFCC and cartilage of the wrist and ulnar variance. The mean ulnar variance on MRI was +0.26 mm (range, -4.59 to +3.71 mm). The mean TFCC angle and TFCC thickness were 23.9 degrees (range, -4.6 to +54.1 degrees ) and 1.11 mm (range, 0.4 to 3.22 mm), respectively. Ulnar variance and TFCC angle were positively correlated (r = 0.84), and ulnar variance and TFCC thickness were negatively correlated (r = -0.71). However, ulnar variance and lunate or ulnar head cartilage thickness were not significantly correlated. CONCLUSION: High resolution MRI with a microscopy coil is a useful tool for evaluating the relationship between ulnar variance and ulnar side structures. PMID- 17729369 TI - Automated method for accurate abdominal fat quantification on water-saturated magnetic resonance images. AB - PURPOSE: To introduce and evaluate the performance of an automated fat quantification method for water-saturated magnetic resonance images. MATERIALS AND METHODS: A fat distribution model is proposed for fat quantification on water saturated magnetic resonance images. Fat from both full- and partial-volume voxels are accounted for in this model based on image intensity histogram analysis. An automated threshold method is therefore proposed to accurately quantify total fat. This method is compared to a traditional full-volume-fat-only method in phantom and human studies. In the phantom study, fat quantification was performed on MR images obtained from a human abdomen oil phantom and was compared with the true oil volumes. In the human study, results of the two fat quantification methods of six subjects were compared on abdominal images with different spatial resolutions. RESULTS: In the phantom study, the proposed method provided significantly more accurate estimations of true oil volumes compared to the reference method (P < 0.0001). In human studies, fat quantification using the proposed method gave much more consistent results on images with different spatial resolutions, and on regions with different degrees of partial volume averaging. CONCLUSION: The proposed automated method is simple, rapid, and accurate for fat quantification on water-saturated MR images. PMID- 17729370 TI - A new EPI-based dynamic field mapping method: application to retrospective geometrical distortion corrections. AB - PURPOSE: To retrospectively correct for geometrical distortions, a new dynamic field mapping method suitable for dynamic single-shot gradient-echo type echo planar imaging (GRE-EPI) is proposed. MATERIALS AND METHODS: The method requires a single volume additional acquisition and allows the extraction of a field map from each phase volume, assuming invariance across time of the echo time independent phase component. Performances of the method are assessed using three sets of experiments: the first tests the prerequisite and the modeling; the second tests the method with time-dependent geometrical distortions; and the third presents a comparison with two other methods. RESULTS: Our results legitimize the modeling procedure and demonstrate that the dynamic method is less sensitive to noise than the other methods. A theoretical explanation for this is proposed in the discussion section. CONCLUSION: Given the minor increase in the acquisition time, this method is well suited for functional magnetic resonance imaging; prospective direction. PMID- 17729371 TI - Frontomaxillary facial angle in chromosomally normal fetuses at 11 + 0 to 13 + 6 weeks. AB - OBJECTIVE: To establish the normal range of the frontomaxillary facial (FMF) angle at 11 + 0 to 13 + 6 weeks of gestation. METHODS: In this prospective study, three-dimensional (3D) volumes of the fetal head were obtained from 500 pregnancies before fetal karyotyping by chorionic villus sampling (CVS), after screening by fetal nuchal translucency (NT) thickness and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 to 13 + 6 weeks. Only cases with a normal karyotype were included in this study. The FMF angle was measured off-line. In a subgroup of 150 cases the FMF angle was measured using 2D ultrasound before obtaining a 3D volume. In 50 cases the 3D volumes were used to measure the FMF angle by the same examiner twice and by another examiner once. RESULTS: The mean FMF angle decreased with crown-rump length (CRL) from 84.3 degrees at CRL 45 mm to 76.5 degrees at CRL 84 mm. There was no significant association between the FMF angle and fetal NT or serum PAPP-A or beta-hCG. In the volumes with paired measurements, the difference between two measurements by the same or two sonographers was < 5% in 95% of the cases. In the cases with paired 3D and 2D ultrasound measurements, the difference in FMF angles was < 8% in 95% of the cases. CONCLUSIONS: At 11 + 0 to 13 + 6 weeks the FMF angle decreases with fetal CRL but is not related to fetal NT or serum biochemistry. The measurement is reproducible and the results obtained by 3D and 2D ultrasound are similar. PMID- 17729372 TI - Frontomaxillary facial angle in fetuses with trisomy 13 at 11 + 0 to 13 + 6 weeks. AB - OBJECTIVE: To investigate the frontomaxillary facial (FMF) angle in fetuses with trisomy 13 at 11 + 0 to 13 + 6 weeks of gestation. METHODS: A three-dimensional (3D) volume of the fetal head was obtained before karyotyping at 11 + 0 to 13 + 6 weeks of gestation in 23 fetuses with trisomy 13. The FMF angle, defined as the angle between the upper surface of the maxilla and the frontal bone in a midsagittal view of the fetal face, was measured and compared to the angle in 500 chromosomally normal fetuses. RESULTS: In 10 of 12 (83.3%) fetuses with trisomy 13 and holoprosencephaly, the FMF angle was above the 95(th) centile of the normal range. In the 11 fetuses with no holoprosencephaly, the FMF angle was not significantly different from normal. There was no significant difference in the FMF angle between the trisomy 13 fetuses with and without facial cleft. CONCLUSIONS: In fetuses with trisomy 13, the FMF angle at 11 + 0 to 13 + 6 weeks of gestation is increased only in cases with associated holoprosencephaly. PMID- 17729373 TI - Hypoplastic left heart syndrome: attitudes among pediatric residents and nurses towards fetal and neonatal management. AB - OBJECTIVE: To determine the attitudes of pediatric residents and nurses towards fetal/neonatal management of hypoplastic left heart syndrome (HLHS), and their basis. METHODS: Pediatric residents and nurses from three cardiac centers completed a survey with hypothetical scenarios in which their own fetuses or newborns had HLHS. While Institution A performs many HLHS surgeries, Institution C performs very few. RESULTS: A total of 43% of residents and 50% of nurses would terminate an affected pregnancy. More experience (4 to 7 years, p = 0.04; >7 years, p = 0.05) and employment at institution C (p = 0.04) predicted termination. Expected better quality of life (QOL) (p = 0.02) and five-year survival >50% (p = 0.06) predicted not terminating. Postnatally, 48% of residents and 68% of nurses would choose, or seriously consider, comfort care. Marriage (p = 0.04) and more experience (4 to 7 years, p = 0.04; >7 years, p = 0.02) predicted choosing comfort care. Asian/Pacific Islander descent (p = 0.01) and expected 5-year survival >50% (p = 0.02) predicted choosing surgery. CONCLUSIONS: Approximately one-half of the pediatric residents and nurses surveyed would choose termination of pregnancy or seriously consider declining neonatal surgery, if their own fetus or infant had HLHS. These attitudes reflect perceptions of long-term QOL and survival. These attitudes may be of interest to caregivers who care for HLHS patients. PMID- 17729374 TI - Prenatal diagnosis of a 11q deletion syndrome associated with unilateral hydronephrosis diagnosed by 3D ultrasound examination. PMID- 17729375 TI - Virtual tool for bilaterally controlled forceps robot--for minimally invasive surgery. AB - BACKGROUND: Bilateral control enables an operator to be placed away from the working environment. A slave manipulator usually works at a remote site or in a hazardous environment while the master operator senses the environment through the slave manipulator. Bilateral control can be used in surgeries. Usually doctors are very sensitive to the tactile sensation they feel through medical tools. If bilateral control is used in a surgery, ideally the doctor should perceive the sensation of both the body tissue and the reaction force from the specialized tool. Many surgical instruments are essentially similar at the tool tip while showing some structural differences at the gripping end. Therefore, it is advantageous for an expensive tool to be replaced by a virtual tool together with a simple tool. With the virtual tool, the surgeon should be able to perceive the feeling of the actual tool together with the reaction force coming from the body tissue; this may also reduce the time taken for a tool change during the surgery. METHODS: In this study, above ideas were implemented in a bilaterally controlled forceps robot and experiments were carried out to test the applicability of the concept. Bilateral control is used as the method of tactile feedback. Disturbance observer is used for robust control. Reaction force observer is used in place of a force sensor. Virtual model is used in place of the special tool properties. RESULTS: A virtual spring acting at the end of the forceps, was implemented to a bilateral control system, so that the operator at the master side could perceive the feeling of the spring together with reaction forces from the surgical environment. Operator could feel the vivid sensation of the environment through the master manipulator. CONCLUSIONS: The virtual model adds a load to the system. The master and slave responses are slightly different, but the result is good enough for the application. This novel approach could be used in many master-slave applications. PMID- 17729376 TI - Computer-assisted navigation applied to fetal cardiac intervention. AB - BACKGROUND: Prenatal cardiac interventions (PCI) for human fetal aortic valve (AoV) stenosis can reduce left ventricular hypoplasia and restore ventricular growth and function. However, 'freehand' needle delivery from the maternal skin through the uterine wall, fetal chest and ventricular apex to cross the fetal AoV remains technically challenging and time intensive, and is the rate-limiting step in the procedure. METHODS: We developed a computer-assisted navigation (CANav) system that tracks the position and orientation of a two-dimensional (2D) ultrasound image relative to the trajectory of an electromagnetic (EM) embedded needle and stylet. We tested the CANav system in vitro using a water bath phantom, then in vivo using adult rats and pregnant (fetal) sheep. RESULTS: The CANav system accurately tracked the delivered needle position in both in vitro phantom and adult rat model experiments. We performed 22 PCI attempts with or without CANav in a fetal sheep model. Maternal laparotomy was required to adjust the fetal position in 50% of the procedures. The time required to deliver the needle from the skin into the left ventricle (LV) using CANav was 2.9 +/- 1.7 (range 2-7) min (n = 14) vs. 5.5 +/- 4.3 (range 1-12) min (n = 8) without CANav (p < 0.05). The time needed to cross the aortic valve once the needle was within the LV was similar with and without CANav (p = 0.19). CONCLUSIONS: CANav reduces the PCI time required to accurately deliver a needle to the fetal heart. Adaptations of this technical approach may be relevant to other congenital cardiac conditions and ultrasound-guided medical procedures. PMID- 17729377 TI - The need for reorientation toward cost-effective prediction: comments on 'Evaluating the added predictive ability of a new marker: From area under the ROC curve to reclassification and beyond' by M. J. Pencina et al., Statistics in Medicine (DOI: 10.1002/sim.2929). PMID- 17729378 TI - Risks of congenital malformations and perinatal events among infants exposed to antidepressant medications during pregnancy. AB - PURPOSE: To evaluate risks for perinatal complications and congenital defects among infants exposed in utero to antidepressants. METHODS: We identified 2201 women who were prescribed an antidepressant during pregnancy and who delivered an infant within one of five large managed care organizations (HMO). Prescription drug dispensings and inpatient and outpatient diagnoses were obtained from automated databases at each HMO. Antidepressants were categorized into tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs), and medication timing was assessed by trimester. Rates of congenital anomalies or perinatal complications were compared to infants whose mothers were not prescribed antidepressants during pregnancy. RESULTS: Infants exposed to SSRIs or TCAs during pregnancy had a significant increase in preterm delivery risk. Fullterm infants exposed to SSRIs during the third trimester had an increased risk for respiratory distress syndrome, endocrine and metabolic disturbances, hypoglycemia, temperature regulation disorders, and convulsions. Third-trimester exposure to TCAs was also associated with an increased risk for respiratory distress syndrome, endocrine and metabolic disturbances, and temperature regulation disorders. There were 182 infants exposed to Paroxetine, and these infants did not have an increased risk of cardiac septal defects. CONCLUSIONS: SSRIs and TCAs did not show a consistent link with congenital anomalies. Paroxetine exposure was not linked with an increased risk for cardiovascular anomalies, although our study power to detect a moderate increase in risk was limited. Infants exposed to antidepressants were at increased risk for preterm delivery. Both SSRIs and TCAs used during the third trimester appeared to increase the risk for perinatal complications and their use should be managed carefully among pregnant women with depression. PMID- 17729379 TI - Paroxetine in the first trimester and the prevalence of congenital malformations. AB - PURPOSE: To refine a preliminary analysis identifying a possibly increased prevalence of malformations among infants born to women exposed to paroxetine in the first trimester. METHODS: This study used data from UnitedHealthcare, a large U.S. insurer, using datasets originally for a study of bupropion in pregnancy. We identified women with a live-born delivery between January 1995 and September 2004. We classified women according to their first trimester mono- or mono/polytherapy exposure to paroxetine and other antidepressants. We confirmed malformation cases by medical record abstraction. We calculated the adjusted odds ratios (AORs) through logistic regression. RESULTS: For paroxetine, there were 815 infants among 791 women exposed as monotherapy, and 1020 infants among 989 women exposed as mono- or polytherapy. For other antidepressants, there were 4198 infants among 4072 women exposed as monotherapy, and 4936 infants among 4767 women exposed as mono- or polytherapy. AORs for all congenital malformations associated with paroxetine were 1.89 (95%CI 1.20-2.98) for monotherapy, and 1.76 (95%CI 1.18-2.64) for mono- or polytherapy. AORs for cardiovascular malformations associated with paroxetine were 1.46 (95%CI 0.74-2.88) for monotherapy, and 1.68 (95%CI 0.95-2.97) for mono- or polytherapy. CONCLUSIONS: These more detailed paroxetine findings confirm previous findings of analyses of these data among women exposed to all types of antidepressants. The present findings are consistent with other recent results suggesting the possibility of a modestly increased occurrence of congenital malformations following first trimester exposure to paroxetine compared to other antidepressants. PMID- 17729380 TI - Navigated surgery in oral implantology: a case study. PMID- 17729381 TI - Efficient generation of constrained block allocation sequences. AB - Selection bias is a potential problem, especially in trials where blinding is not possible. Randomization with a constrained block of large size provides better protection from selection bias than using a sequence of blocks of small size with the same maximum imbalance. We propose an algorithm that efficiently generates constrained block allocation sequences, and we describe two clinical trials in which such a constrained randomization was used. PMID- 17729382 TI - Identification of lignans by liquid chromatography-electrospray ionization ion trap mass spectrometry. AB - The fragmentation pattern of 30 compounds belonging to different classes of the lignan family was studied by liquid chromatography-electrospray ionization ion trap mass spectrometry. On the basis of the observed fragmentation patterns, identification of different types of lignans was achieved. For example, dibenzylbutyrolactone lignans showed a characteristic fragmentation pathway by the loss of 44 Da (CO(2)) from the lactone moiety, whereas dibenzylbutanediols showed a loss of 48 Da by a combined loss of formaldehyde and water from the 1,4 butanediol moiety. Lignan glycosides readily lost the sugar residue to give the parent lignan as their primary product ion. In addition, several compound specific fragmentations were observed and used for identification of individual compounds.A versatile method for analyses of lignans was developed using LC separation on a C8 column followed by fragmentation and detection of ions produced in the ion trap. PMID- 17729383 TI - Negative electrospray ionization tandem mass spectrometric investigation of ent kaurane diterpenoids from the genus Isodon. AB - ent-Kaurane diterpenoids are a class of natural compounds isolated from genus Isodon, which have been found to have important bioactivities. Negative electrospray ionization tandem mass spectrometry ((-)ESI-MS(n)) was used to investigate the fragmentation pattern of C-20-nonoxygenated ent-kauranes and two subtypes of C-20-oxygenated ent-kauranes by using an ion trap instrument and accurate mass measurement on an ESI-Q-time-of-flight (TOF) mass spectrometer. The analysis revealed that loss of CH(2)O or CO(2) is the predominant process for 7, 20-epoxy and 7, 20 : 14, 20-diepoxy subgroup of C-20-oxygenated ent-kauranes. In addition, compounds of C-20-nonoxygenated ent-kauranes with a conserved core structure but different substituent groups, such as a hydroxyl, aldehyde, carboxyl, and acetyl moiety, resulted in diagnostic product ions through losses of H(2)O, CO, CO(2), and AcOH, respectively. This work clearly demonstrates the utility of tandem mass spectrometry for studies on the rationalization of the diagnostic fragmentation of a series of compounds from two main types of the ent kaurane diterpenoids. PMID- 17729384 TI - Meta-analysis of holmium laser enucleation versus transurethral resection of the prostate for symptomatic prostatic obstruction. AB - BACKGROUND: Holmium laser enucleation (HoLEP) is an alternative to transurethral resection (TURP) of the prostate for symptomatic prostatic obstruction. METHODS: Randomized controlled trials comparing HoLEP and TURP were identified systematically using Medline, Embase and The Cochrane Library. Primary outcomes were peak urinary flow rate (Qmax), postvoid residual volume, symptom score and quality of life. Secondary outcomes were duration of operation, hospital stay, blood loss, catheterization time and adverse events. RESULTS: There was no statistically significant difference between HoLEP and TURP in terms of Qmax at 6 and 12 months' follow-up. HoLEP was associated with significantly less blood loss, a shorter catheterization time and a shorter hospital stay. TURP was associated with reduced operating time. The techniques were similar in terms of urethral stricture, stress incontinence, transfusion requirement and rate of reintervention. CONCLUSION: HoLEP and TURP provide a similar improvement in Qmax. HoLEP, however, has several advantages over TURP, despite requiring more operating time. It is at least as safe as TURP in terms of adverse events. PMID- 17729385 TI - Open-label steady-state pharmacokinetic drug interaction study on co-administered quetiapine fumarate and divalproex sodium in patients with schizophrenia, schizoaffective disorder, or bipolar disorder. AB - OBJECTIVE: To determine whether there is a pharmacokinetic drug interaction between quetiapine fumarate and divalproex sodium. METHODS: The pharmacokinetics and short-term tolerability and safety of coadministered quetiapine and divalproex were examined in adults with schizophrenia/schizoaffective disorder (Cohort A) or bipolar disorder (Cohort B) in an open-label, parallel, 2-cohort drug-interaction study conducted at three centers in the United States. Cohort A was administered quetiapine (150 mg bid) prospectively for 13 days, with divalproex (500 mg bid) added on days 6-13. Cohort B was administered divalproex (500 mg bid) for 16 days, with quetiapine (150 mg bid) added on days 9-16. Quetiapine and valproic acid plasma concentration-time data over a 12-h steady state dosing interval were used to determine C(max), T(max), C(min), area under the plasma concentration-time curve (AUC(tau)), and oral clearance (CL/F). RESULTS: In Cohort A (n = 18), addition of divalproex did increase the C(max) of quetiapine by 17% but did not change AUC(tau). In Cohort B (n = 15), addition of quetiapine decreased both total valproic acid C(max) and AUC(tau) by 11%. No differences were observed in adverse events (AEs) with either quetiapine or divalproex monotherapy or their combination. CONCLUSION: Combination therapy with quetiapine (150 mg bid) and divalproex (500 mg bid) resulted in small and statistically non-significant pharmacokinetic changes. PMID- 17729386 TI - Pregnancy following preimplantation genetic diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). AB - OBJECTIVE: Presentation of a novel case, involving the design and implementation of preimplantation genetic diagnosis (PGD) for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: The disease-causing mutation, c.459C>T (R153C) in exon 4 of the Notch3 gene, was previously identified in the affected father. The family already had a pregnancy termination following prenatal diagnosis and chose to undergo PGD. A PGD protocol was designed to include informative, linked short tandem repeat (STR) markers and an intragenic single nucleotide polymorphism (SNP), coupled to mutation identification. Biopsy was performed at day 3 and blastocysts were transferred on day 5 after fertilization. Standard prenatal diagnosis procedures were employed to confirm the PGD results. RESULTS: One blastomere was removed at day 3 from each of eight embryos. Detection of the c.459C>TNotch3 mutation, coupled to informative polymorphic markers, unambiguously identified three unaffected embryos. Blastocyst transfer resulted in a singleton pregnancy and subsequent prenatal diagnosis confirmed that the fetus was disease-free. CONCLUSIONS: Given the dominant, highly penetrant and potentially serious effects of Notch3 mutations, PGD for CADASIL may be considered and implemented as a reproductive option, following proper genetic counseling. PMID- 17729387 TI - How labile is gastric infection with H pylori? AB - It is known that patients infected with H pylori can spontaneously become free from infection, and that the reverse change can occur. The time-scale of these conversions is expressed as percentages per year. Since they have been investigated in terms of serology, the changes are called sero-reversion and sero conversion respectively. Using serological evidence to investigate these phenomena is open to the criticisms that positive serology can be present in the absence of all other evidence of infection, and that a time-lag of 6-12 mo or longer can occur between eradication of the infection and sero-reversion. Investigations using direct evidence of current infection are sparse. The few that exist suggest that some individuals can seroconvert or sero-revert within six to twelve weeks. If these findings are confirmed, it means that some patients have an ability that is variable in time to resist, or spontaneously recover from, H pylori infection. Evidence suggests that the deciding factor of susceptibility is the level of gastric secretion of acid. PMID- 17729388 TI - Should nonalcoholic fatty liver disease be regarded as a hepatic illness only? AB - The highly increasing prevalence of obesity and type 2 diabetes mellitus in the general population makes nonalcoholic fatty liver disease the most common diagnosis in every-day practices. Lifestyle changes (mainly exercise withdrawal and weight gain) have probably heightened the prevalence of nonalcoholic fatty liver disease. Mortality in patients with Nonalcoholic Fatty Liver Disease is significantly higher when compared with that of the same age-gender general population. Hepatologists claim to bear a new burden, being Nonalcoholic Fatty Liver Disease strongly linked to systemic diseases. PMID- 17729390 TI - Non-HFE haemochromatosis. AB - Non-HFE hereditary haemochromatosis (HH) refers to a genetically heterogeneous group of iron overload disorders that are unlinked to mutations in the HFE gene. The four main types of non-HFE HH are caused by mutations in the hemojuvelin, hepcidin, transferrin receptor 2 and ferroportin genes. Juvenile haemochromatosis is an autosomal recessive disorder and can be caused by mutations in either hemojuvelin or hepcidin. An adult onset form of HH similar to HFE-HH is caused by homozygosity for mutations in transferrin receptor 2. The autosomal dominant iron overload disorder ferroportin disease is caused by mutations in the iron exporter ferroportin. The clinical characteristics and molecular basis of the various types of non-HFE haemochromatosis are reviewed. The study of these disorders and the molecules involved has been invaluable in improving our understanding of the mechanisms involved in the regulation of iron metabolism. PMID- 17729389 TI - HFE gene in primary and secondary hepatic iron overload. AB - Distinct from hereditary haemochromatosis, hepatic iron overload is a common finding in several chronic liver diseases. Many studies have investigated the prevalence, distribution and possible contributory role of excess hepatic iron in non-haemochromatotic chronic liver diseases. Indeed, some authors have proposed iron removal in liver diseases other than hereditary haemochromatosis. However, the pathogenesis of secondary iron overload remains unclear. The High Fe (HFE) gene has been implicated, but the reported data are controversial. In this article, we summarise current concepts regarding the cellular role of the HFE protein in iron homeostasis. We review the current status of the literature regarding the prevalence, hepatic distribution and possible therapeutic implications of iron overload in chronic hepatitis C, hepatitis B, alcoholic and non-alcoholic fatty liver diseases and porphyria cutanea tarda. We discuss the evidence regarding the role of HFE gene mutations in these liver diseases. Finally, we summarize the common and specific features of iron overload in liver diseases other than haemochromatosis. PMID- 17729391 TI - Iron overload and cofactors with special reference to alcohol, hepatitis C virus infection and steatosis/insulin resistance. AB - There are several cofactors which affect body iron metabolism and accelerate iron overload. Alcohol and hepatic viral infections are the most typical examples for clarifying the role of cofactors in iron overload. In these conditions, iron is deposited in hepatocytes and Kupffer cells and reactive oxygen species (ROS) produced through Fenton reaction have key role to facilitate cellular uptake of transferrin-bound iron. Furthermore, hepcidin, antimicrobial peptide produced mainly in the liver is also responsible for intestinal iron absorption and reticuloendothelial iron release. In patients with ceruloplasmin deficiency, anemia and secondary iron overload in liver and neurodegeneration are reported. Furthermore, there is accumulating evidence that fatty acid accumulation without alcohol and obesity itself modifies iron overload states. Ineffective erythropoiesis is also an important factor to accelerate iron overload, which is associated with diseases such as thalassemia and myelodysplastic syndrome. When this condition persists, the dietary iron absorption is increased due to the increment of bone marrow erythropoiesis and tissue iron overload will thereafter occurs. In porphyria cutanea tarda, iron is secondarily accumulated in the liver. PMID- 17729392 TI - Iron overload and immunity. AB - Progress in the characterization of genes involved in the control of iron homeostasis in humans and in mice has improved the definition of iron overload and of the cells affected by it. The cell involved in iron overload with the greatest effect on immunity is the macrophage. Intriguing evidence has emerged, however, in the last 12 years indicating that parenchymal iron overload is linked to genes classically associated with the immune system. This review offers an update of the genes and proteins relevant to iron metabolism expressed in cells of the innate immune system, and addresses the question of how this system is affected in clinical situations of iron overload. The relationship between iron and the major cells of adaptive immunity, the T lymphocytes, will also be reviewed. Most studies addressing this last question in humans were performed in the clinical model of Hereditary Hemochromatosis. Data will also be reviewed demonstrating how the disruption of molecules essentially involved in adaptive immune responses result in the spontaneous development of iron overload and how they act as modifiers of iron overload. PMID- 17729393 TI - Molecular mechanisms involved in intestinal iron absorption. AB - Iron is an essential trace metal in the human diet due to its obligate role in a number of metabolic processes. In the diet, iron is present in a number of different forms, generally described as haem (from haemoglobin and myoglobin in animal tissue) and non-haem iron (including ferric oxides and salts, ferritin and lactoferrin). This review describes the molecular mechanisms that co-ordinate the absorption of iron from the diet and its release into the circulation. While many components of the iron transport pathway have been elucidated, a number of key issues still remain to be resolved. Future work in this area will provide a clearer picture regarding the transcellular flux of iron and its regulation by dietary and humoral factors. PMID- 17729395 TI - Liver-gut axis in the regulation of iron homeostasis. AB - The human body requires about 1-2 mg of iron per day for its normal functioning, and dietary iron is the only source for this essential metal. Since humans do not possess a mechanism for the active excretion of iron, the amount of iron in the body is determined by the amount absorbed across the proximal small intestine and, consequently, intestinal iron absorption is a highly regulated process. In recent years, the liver has emerged as a central regulator of both iron absorption and iron release from other tissues. It achieves this by secreting a peptide hormone called hepcidin that acts on the small intestinal epithelium and other cells to limit iron delivery to the plasma. Hepcidin itself is regulated in response to various systemic stimuli including variations in body iron stores, the rate of erythropoiesis, inflammation and hypoxia, the same stimuli that have been known for many years to modulate iron absorption. This review will summarize recent findings on the role played by the liver and hepcidin in the regulation of body iron absorption. PMID- 17729394 TI - Liver iron transport. AB - The liver plays a central role in iron metabolism. It is the major storage site for iron and also expresses a complex range of molecules which are involved in iron transport and regulation of iron homeostasis. An increasing number of genes associated with hepatic iron transport or regulation have been identified. These include transferrin receptors (TFR1 and 2), a ferrireductase (STEAP3), the transporters divalent metal transporter-1 (DMT1) and ferroportin (FPN) as well as the haemochromatosis protein, HFE and haemojuvelin (HJV), which are signalling molecules. Many of these genes also participate in iron regulatory pathways which focus on the hepatic peptide hepcidin. However, we are still only beginning to understand the complex interactions between liver iron transport and iron homeostasis. This review outlines our current knowledge of molecules of iron metabolism and their roles in iron transport and regulation of iron homeostasis. PMID- 17729397 TI - Pathology of hepatic iron overload. AB - Although progress in imaging and genetics allow for a noninvasive diagnosis of most cases of genetic iron overload, liver pathology remains often useful (1) to assess prognosis by grading fibrosis and seeking for associated lesions and (2) to guide the etiological diagnosis, especially when no molecular marker is available. Then, the type of liver siderosis (parenchymal, mesenchymal or mixed) and its distribution throughout the lobule and the liver are useful means for suggesting its etiology: HLA-linked hemochromatosis gene (HFE) hemochromatosis or other rare genetic hemochromatosis, nonhemochromatotic genetic iron overload (ferroportin disease, aceruloplasminemia), or iron overload secondary to excessive iron supply, inflammatory syndrome, noncirrhotic chronic liver diseases including dysmetabolic iron overload syndrome, cirrhosis, and blood disorders. PMID- 17729396 TI - Role of iron in hepatic fibrosis: one piece in the puzzle. AB - Iron is an essential element involved in various biological pathways. When present in excess within the cell, iron can be toxic due to its ability to catalyse the formation of damaging radicals, which promote cellular injury and cell death. Within the liver, iron related oxidative stress can lead to fibrosis and ultimately to cirrhosis. Here we review the role of excessive iron in the pathologies associated with various chronic diseases of the liver. We also describe the molecular mechanism by which iron contributes to the development of hepatic fibrosis. PMID- 17729398 TI - Inhibition of histone deacetylase for the treatment of biliary tract cancer: a new effective pharmacological approach. AB - AIM: To investigate in vitro and in vivo therapeutic effects of histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589 on biliary tract cancer. METHODS: Cell growth inhibition by NVP-LAQ824 and NVP-LBH589 was studied in vitro in 7 human biliary tract cancer cell lines by MTT assay. In addition, the anti tumoral effect of NVP-LBH589 was studied in a chimeric mouse model. Anti-tumoral drug mechanism was assessed by immunoblotting for acH4 and p21( WAF-1/CIP-1), PARP assay, cell cycle analysis, TUNEL assay, and immunhistochemistry for MIB-1. RESULTS: In vitro treatment with both compounds significantly suppressed the growth of all cancer cell lines [mean IC(50) (3 d) 0.11 and 0.05 micromol/L, respectively], and was associated with hyperacetylation of nucleosomal histone H4, increased expression of p21( WAF-1/CIP-1), induction of apoptosis (PARP cleavage), and cell cycle arrest at G2/M checkpoint. After 28 d, NVP-LBH589 significantly reduced tumor mass by 66% (bile duct cancer) and 87% (gallbladder cancer) in vivo in comparison to placebo, and potentiated the efficacy of gemcitabine. Further analysis of the tumor specimens revealed increased apoptosis by TUNEL assay and reduced cell proliferation (MIB-1). CONCLUSION: Our findings suggest that NVP-LBH589 and NVP-LAQ824 are active against human biliary tract cancer in vitro. In addition, NVP-LBH589 demonstrated significant in vivo activity and potentiated the efficacy of gemcitabine. Therefore, further clinical evaluation of this new drug for the treatment of biliary tract cancer is recommended. PMID- 17729399 TI - Increasing dietary fiber intake in terms of kiwifruit improves constipation in Chinese patients. AB - AIM: To investigate if increased dietary fiber, in terms of kiwifruit, is effective in Chinese constipated patients. METHODS: 33 constipated patients and 20 healthy volunteers were recruited for a 4-wk treatment of kiwi fruit twice daily. Response during wk 1-4 was defined as an increase in complete spontaneous bowl, motion (CSBM) > or = 1/wk. Secondary efficacy included response during wk 1 4, individual symptoms and scores of bowel habits and constipation. Responses were compared with the baseline run-in period. Colonic transit time and anorectal manometry were performed before and after treatment. RESULTS: Responder rate was 54.5% in the constipated group. The mean CSBM increased after treatment (2.2 +/- 2.6 vs 4.4 +/- 4.6, P = 0.013). There was also improvement in the scores for bothersomeness of constipation (P = 0.02), and satisfaction of bowel habit (P = 0.001), and decreased in days of laxative used (P = 0.003). There was also improvement in transit time (P = 0.003) and rectal sensation (P < 0.05). However, there was no change in the bowel symptoms or anorectal physiology in the healthy subjects. CONCLUSION: Increasing dietary fiber intake is effective in relieving chronic constipation in Chinese population. PMID- 17729401 TI - Gastric adenocarcinoma with features of endodermal sinus tumor. AB - Extragonadal germ cell tumors are rare. The most common sites for EGGCTs are in midline locations such as the mediastinum, retroperitoneum and pineal gland. These tumors rarely present in the stomach. We describe here a case where a middle aged man presented with typical symptoms of gastric cancer. After extensive workup, which included blood work, CT abdomen scan, upper endoscopy, and endoscopic ultrasound, the patient was diagnosed with gastric cancer. However, due to very high blood levels of alpha-fetoprotein, the specimen was sent for special histochemical staining, which demonstrated that the tumor had features of both adenocarcinoma and endodermal sinus tumor. This is a very aggressive tumor with a very poor prognosis. PMID- 17729400 TI - Distribution of solitary lymph nodes in primary gastric cancer: a retrospective study and clinical implications. AB - AIM: To investigate the distribution pathway of metastatic lymph nodes in gastric carcinoma as a foundation for rational lymphadenectomy. METHODS: We investigated 173 cases with solitary or single station metastatic lymph nodes (LN) from among 2476 gastric carcinoma patients. The location of metastatic LN, histological type and growth patterns were analyzed retrospectively. RESULTS: Of 88 solitary node metastases cases, 65 were limited to perigastric nodes (N(1)), while 23 showed skipping metastasis. Among 8 tumors in the upper third stomach, 3 involved right paracardial LN (station number: No.1), and one in the greater curvature was found in No.1. In the 28 middle third stomach tumors, 10 were found in LN of the lesser curvature (No.3) and 6 in LN of the left gastric artery (No.7); 5 of the 20 cases on the lesser curvature spread to No.7, while 2 of the 8 on the greater curvature metastasized to LN of the spleen hilum (No.10). Of 52 lower third stomach tumors, 13 involved in No.3 and 19 were detected in inferior pyloric LN (No.6); 9 of the 29 cases along the lesser curvature were involved in No.6. CONCLUSION: Transversal and skipping metastases of sentinel lymph nodes (SLN) are notable, and rational lymphadenectomy should, therefore, be performed. PMID- 17729402 TI - Can Campylobacter jejuni play a role in development of celiac disease? A hypothesis. AB - Celiac disease (CD) is an entropathy with malabsortive condition in which an allergic reaction to the cereal grain-protein (gluten) causes small intestine mucosal injury. CD is a multifactorial disorder in which both genetic and environmental factors contribute to the disease development. Mechanisms have been described to explain the pathology of CD. T cells specific for multiple gluten peptides are found in virtually all patients. Generation of such a broad T cell response may be a prerequisite for disease development. CD is associated with multiple extraintestinal presentations, including neurological deficits. Recent studies have shown a significant correlation between anti-ganglioside antibodies and neurological disorders in patients with underlying CD. Gangliosides are glycosphingolipids which are abundant in nervous system and in other tissues including gastrointestinal tract. It is not known what triggers the release of anti-ganglioside antibodies in people with gluten sensitivity. But, the mechanism is likely to involve the intestinal immune system response to ingested gliadin, a component of wheat gluten. Studies showed that mechanisms different from gluten exposure may be implicated in antibody formation, and other environmental factors may also exist. In addition, considering the fact that genetic predisposition dysregulating mucosal immune responses in the presence of certain environmental triggers like gastrointestinal infections may be strong etiological factors for developing chronic intestinal inflammation including CD, the hypothesis raised in our mind that antiganglioside antibody formation in CD may play a role not only in development of neurological complications in celiac patients, but also in development of CD itself. As presence of Campylobacter jejuni in other diseases with antigangliosides antibody formation has been established, we propose the possible role of Campylobacter jejuni in development of CD in association with other genetic and environmental factors by the mechanism that molecular mimicry of gangliosides-like epitopes common to both lipo-polysacharide coats of certain strains of Campylobacter jejuni and gangliosides in cell structure of gastrointestinal mucosa may cause an autoimmune response and consequently lead to atrophy and degeneration of mucosa possibly by apoptosis. PMID- 17729404 TI - Capsule endoscopy: current status in obscure gastrointestinal bleeding. AB - Capsule endoscopy (CE) is a safe, non invasive diagnostic modality for the evaluation of small bowel lesions. Obscure gastrointestinal bleeding (OGIB) is one of the most important indications of capsule endoscopy. Capsule endoscopy has a very high diagnostic yield especially if the bleeding is ongoing. This technique appears to be superior to other techniques for the detection of suspected lesions and the source of bleeding. Capsule endoscopy has been shown to change the outcome in patients with obscure gastrointestinal (GI) bleed. PMID- 17729405 TI - Expression of PTEN, PPM1A and P-Smad2 in hepatocellular carcinomas and adjacent liver tissues. AB - AIM: To investigate the expressions of PTEN, PPM1A and P-Smad2 in hepatocellular carcinoma (HCC) and their significance. METHODS: The expressions of PTEN, PPM1A and P-Smad2 in 31 HCC tissues, 25 adjacent liver tissues and 13 non-tumor liver tissues were detected by using Envision immunohistochemical technique. RESULTS: The positive expression (64.52%) and staining intensity (4.19 +/- 3.31) of PTEN in the cytoplasm of HCC were significantly lower and weaker than those in the adjacent or non-tumor liver tissues (97.37%, 7.88 +/- 0.93; 100%, 7.77 +/- 0.93, respectively) (P < 0.05), and its staining intensity in the cytoplasm of HCC, which belongs to Edmondson pathologic grades II-III and above, was also lower than that of grade I and I-II. Furthermore, its location in the nucleus or cytoplasm of liver cells was negatively correlated with the progression of liver disease (r = -0.339, P = 0.002); most of PPM1A might be only expressed in the nucleus of adjacent liver tissues, non-HCC tissues or Edmondson grade I and I-II HCC, but it was mainly expressed in the cytoplasm of HCC with Edmondson grade > or = II, weakly or negatively expressed in the nucleus (P < 0.05), and its location was negatively correlated with the progression of liver disease (r = 0.45, P = 0.0000). P-Smad2, which was mostly located in the nucleus and cytoplasm of grade I and I-II HCC, surrounding or non-tumor liver tissues, was only in the nucleus of HCC with Edmondson grade II and above (P < 0.001), and its location was positively correlated with the disease progression (r = 0.224, P = 0.016). Spearman correlation analysis revealed that P-Smad2 was significantly negatively correlated with PTEN and PPM1A (r = -0.748, P = 0.000; r = -0.366, P = 0.001, respectively); and PTEN and PPM1A were positively correlated with HCC carcinogenesis (r = 0.428, P = 0.000). CONCLUSION: The aberrant location of expression and staining intensity of PTEN, PPM1A and P-Smad2 in HCC and their relationship might have an impact on the pathogenesis of HCC. PMID- 17729403 TI - Pathogenesis and management issues for non-alcoholic fatty liver disease. AB - Nonalcoholic fatty liver disease (NAFLD) has, although it is a very common disorder, only relatively recently gained broader interest among physicians and scientists. Fatty liver has been documented in up to 10 to 15 percent of normal individuals and 70 to 80 percent of obese individuals. Although the pathophysiology of NAFLD is still subject to intensive research, several players and mechanisms have been suggested based on the substantial evidence. Excessive hepatocyte triglyceride accumulation resulting from insulin resistance is the first step in the proposed 'two hit' model of the pathogenesis of NAFLD. Oxidative stress resulting from mitochondrial fatty acids oxidation, NF-kappaB dependent inflammatory cytokine expression and adipocytokines are all considered to be the potential factors causing second hits which lead to hepatocyte injury, inflammation and fibrosis. Although it was initially believed that NAFLD is a completely benign disorder, histologic follow-up studies have showed that fibrosis progression occurs in about a third of patients. A small number of patients with NAFLD eventually ends up with end-stage liver disease and even hepatocellular carcinoma. Although liver biopsy is currently the only way to confirm the NAFLD diagnosis and distinguish between fatty liver alone and NASH, no guidelines or firm recommendations can still be made as for when and in whom it is necessary. Increased physical activity, gradual weight reduction and in selected cases bariatric surgery remain the mainstay of NAFLD therapy. Studies with pharmacologic agents are showing promising results, but available data are still insufficient to make specific recommendations; their use therefore remains highly individual. PMID- 17729406 TI - Different natural courses of chronic hepatitis B with genotypes B and C after the fourth decade of life. AB - AIM: To investigate the different impact of genotypes B and C on the development of liver cirrhosis (LC) among different age groups of patients with chronic hepatitis B (CH-B). METHODS: We examined the outcome of 121 patients with CH-B, divided by age and genotype. Univariate analyses were used to compare different groups. The Cox proportional hazard model was employed to evaluate factors affecting the development of LC. RESULTS: In patients < 30 years old, there were no significant predictors for development of LC. However, in patients > or = 30 years old, genotype C was the only significant predictor. In the genotype C group, 8 of 12 patients who progressed to LC were 30-49 years old at initial diagnosis of chronic hepatitis (7 patients were positive for HBeAg). In the genotype B group, 4 of 8 patients who developed LC were > or = 50 years old at initial diagnosis and were HBeAg-negative. CONCLUSION: The rate of development of LC was comparable in patients infected with genotypes B and C when CH-B occurred at < 30 years old. However, CH-B patients infected with genotype C showed poor prognosis if they were 30-49 years old and were positive for HBeAg. Age-specific natural course of CH-B should be considered when patients with CH-B are treated with antiviral drugs. PMID- 17729408 TI - Infectious causation of chronic disease: examining the relationship between Giardia lamblia infection and irritable bowel syndrome. AB - AIM: To evaluate whether a higher prevalence of Giardia lamblia infection is associated with an increase in irritable bowel syndrome (IBS) prescriptions at the county level in Michigan. METHODS: The Michigan Disease Surveillance System (MDSS) was used to ascertain both the numbers of Giardia lamblia infections as well as the total number of foodborne illnesses per population by county in Michigan during 2005. This was compared with Blue Cross Blue Shield (BCBS) of Michigan numbers of drug prescriptions for IBS per one thousand members per county in 2005. These data were also analyzed for associations with per capita income by county and the number of refugees entering each county in 2005. RESULTS: There were a total of 786 confirmed cases of Giardia lamblia reported to MDSS in 2005. During the same time period, the number of prescriptions for IBS varied from 0.5 per 1000 members up to 6.0 per 1000 members per month. There was no trend towards higher numbers of IBS prescriptions in the counties with more Giardia lamblia infections. Per capita income was not associated with either IBS prescriptions or Giardiasis. There was a significant linear association between the number of refugees entering each county, and the number of Giardia lamblia cases per 100,000 population. CONCLUSION: In this ecological study, there was no association found between BCBS prescriptions for IBS and Giardia lamblia infections in Michigan counties. Our findings may have been influenced by the disparate number of refugees admitted per county. PMID- 17729407 TI - Preparation method of an ideal model of multiple organ injury of rat with severe acute pancreatitis. AB - AIM: To establish an ideal model of multiple organ injury of rats with severe acute pancreatitis (SAP). METHODS: SAP models were induced by retrograde injection of 0.1 mL/100 g 3.5% sodium taurocholate into the biliopancreatic duct of Sprague-Dawley rats. The plasma and samples of multiple organ tissues of rats were collected at 3, 6 and 12 h after modeling. The ascites volume, ascites/body weight ratio, and contents of amylase, endotoxin, endothelin-1 (ET-1), nitrogen monoxidum (NO), phospholipase A(2) (PLA(2)), tumor necrosis factor-alpha (TNF alpha), interleukin-6 (IL-6) in plasma were determined. The histological changes of multiple organs were observed under light microscope. RESULTS: The ascites volume, ascites/body weight ratio, and contents of various inflammatory mediators in blood were higher in the model group than in the sham operation group at all time points [2.38 (1.10), 2.58 (0.70), 2.54 (0.71) vs 0.20 (0.04), 0.30 (0.30), 0.22 (0.10) at 3, 6 and 12 h in ascites/body weight ratio; 1582 (284), 1769 (362), 1618 (302) (U/L) vs 5303 (1373), 6276 (1029), 7538 (2934) (U/L) at 3, 6 and 12 h in Amylase; 0.016 (0.005), 0.016 (0.010), 0.014 (0.015) (EU/mL) vs 0.053 (0.029), 0.059 (0.037), 0.060 (0.022) (EU/mL) at 3, 6 and 12 h in Endotoxin; 3.900 (3.200), 4.000 (1.700), 5.300 (3.000) (ng/L) vs 41.438 (37.721), 92.151 (23.119), 65.016 (26.806) (ng/L) at 3, 6 and 12 h in TNF-alpha, all P < 0.01]. Visible congestion, edema and lamellar necrosis and massive leukocytic infiltration were found in the pancreas of rats of model group. There were also pathological changes of lung, liver, kidney, spleen, ileum, lymphonode, thymus, myocardium and brain. CONCLUSION: This rat model features reliability, convenience and a high achievement ratio. Complicated with multiple organ injury, it is an ideal animal model of SAP. PMID- 17729410 TI - Hypoestoxide inhibits tumor growth in the mouse CT26 colon tumor model. AB - AIM: To evaluate the effect of the natural diterpenoid, hypoestoxide (HE) on the growth of established colon cancer in mice. METHODS: The CT26.WT mouse colon carcinoma cell line was grown and expanded in vitro. Following the expansion, BALB/c mice were inoculated s.c. with viable tumor cells. After the tumors had established and developed to about 80-90 mm(3), the mice were started on chemotherapy by oral administration of HE, 5-fluorouracil (5-FU) or combination. RESULTS: The antiangiogenic HE has previously been shown to inhibit the growth of melanoma in the B16F(1) tumor model in C57BL/6 mice. Our results demonstrate that mean volume of tumors in mice treated with oral HE as a single agent or in combination with 5-FU, were significantly smaller (> 60%) than those in vehicle control mice (471.2 mm(3) vs 1542.8 mm(3), P < 0.01). The significant reductions in tumor burden resulted in pronounced mean survival times (MST) and increased life spans (ILS) in the treated mice. CONCLUSION: These results indicate that HE is an effective chemotherapeutic agent for colorectal cancer in mice and that HE may be used alone or in combination with 5-FU. PMID- 17729411 TI - Gastrectomy for patients with gastric cancer and non-uremic renal failure. AB - AIM: To investigate the safety and outcome of gastrectomy for patients with gastric cancer and non-uremic renal failure (NURF). METHODS: One hundred forty seven patients who underwent gastrectomy for carcinoma were retrospectively divided into two groups: a group with Ccr values of > or = 50 mL/min (Group 1; n = 110), and one with Ccr values of > or = 20 to < 50 mL/min (Group 2; n = 37). Preoperative patient characteristics, intraoperative parameters (including operation time and blood loss), and postoperative management and complications were evaluated. RESULTS: There were no statistically significant differences between the two groups in operation time (297.9 min vs 272.6 min, P = 0.137) or blood loss (435 mL vs 428 mL, P = 0.078). The differences in postoperative complications and hospital stay between the groups were not statistically significant. None of the patients in Group 2 required dialysis therapy, and no patients died due to gastrectomy or gastrectomy-related causes. The overall 4 year survival rates in Groups 1 and 2 were 86.6% and 81.8%, respectively (P = 0.48), and the corresponding 4-year disease-free survival rates for stage I, II, and III patients were 88.7% and 83.5%, respectively (P = 0.65). CONCLUSION: Gastrectomy can be performed as safely in patients with NURF similar to patients with normal renal function. PMID- 17729409 TI - Prognostic value of (13)C-phenylalanine breath test on predicting survival in patients with chronic liver failure. AB - AIM: To evaluate the prognostic value of percentage of (13)C-phenylalanine oxidation ((13)C-PheOx) obtained by (13)C-phenylalanine breath test ((13)C-PheBT) on the survival of patients with chronic liver failure. METHODS: The hepatic function was determined by standard liver blood tests and the percentage of (13)C PheOx in 118 chronic liver failure patients. The follow-up period was of 64 mo. Survival analysis was performed by the Kaplan-Meier method and variables that were significant (P < 0.10) in univariate analysis and subsequently introduced in a multivariate analysis according to the hazard model proposed by Cox. RESULTS: Forty-one patients died due to progressive liver failure during the follow-up period. The probability of survival at 12, 24, 36, 48 and 64 mo was 0.88, 0.78, 0.66, 0.57 and 0.19, respectively. Multivariate analysis demonstrated that Child Pugh classes, age, creatinine and the percentage of (13)C-PheOx (HR 0.338, 95% CI: 0.150-0.762, P = 0.009) were independent predictors of survival. When Child Pugh classes were replaced by all the parameters of the score, only albumin, bilirubin, creatinine, age and the percentage of (13)C-PheOx (HR 0.449, 95% CI: 0.206-0.979, P = 0.034) were found to be independent predictors of survival. CONCLUSION: Percentage of (13)C-PheOx obtained by (13)C-PheBT is a strong predictor of survival in patients with chronic liver disease. PMID- 17729412 TI - Elucidation of the relationship of BNIP3 expression to gemcitabine chemosensitivity and prognosis. AB - AIM: To evaluate the significance of BNIP3 in the pathogenesis of pancreatic cancer, we analyzed the relationship between the expression of BNIP3 and survival rate of the patients with pancreatic cancer, or chemosensitivities in pancreatic cancer cell lines, particularly for gemcitabine, the first-line anti-tumor drug for pancreatic cancer. METHODS: To compare the expression level of BNIP3 with the resistance to gemcitabine, eight pancreatic cancer cell lines were subjected to gemcitabine treatment and the quantitative real-time RT-PCR method was used to evaluate BNIP3 expression. Immunohistochemical analysis was also performed using 22 pancreatic cancer specimens to study relationship between BNIP3 expression and survival rate. RESULTS: Although no significantly positive association between BNIP3 mRNA level and gemcitabine chemosensitivity was observed, pancreatic cancer cell lines that were sensitive to gemcitabine treatment tended to show high levels of BNIP3 expression. The converse, an absence of BNIP3 expression, was not correlated with gemcitabine resistance. We further compared the BNIP3 expression profiles of resected primary pancreatic cancer specimens with the prognosis of the patients, and found a tendency of favorable prognosis and low BNIP3 expression. CONCLUSION: High levels of BNIP3 expression cannot be used as one of the predicting factors for gemcitabine chemosensitivity, and some yet to be known factors will have to fill the gap for the accurate prediction of pancreatic cancer chemosensitivity to gemcitabine. However, BNIP3 expression may have an impact on prediction of prognosis of patients with pancreatic cancer. PMID- 17729413 TI - Dyslipidemia and H pylori in gastric xanthomatosis. AB - AIM: To investigate the relationship among gastric xanthomatosis (GX), H pylori, dyslipidemia, and gastritis in Korea, a well-known H pylori endemic area. METHODS: A total of 771 patients who had undergone gastroduodenoscopy by one endoscopist were included in this study. Among them, 54 patients with GX were assessed for H pylori infection and their endoscopic characteristics and serum lipid profiles. The findings were compared with 54 age- and sex-matched control subjects without GX. RESULTS: The prevalence of GX was 7% (54/771) with no sex difference. GX was mainly single (64.8%) and located in the antrum (53.7%). The mean diameter was 7 +/- 3 mm. Mean body mass index (BMI) of patients with GX was 23.1 +/- 2.8 and no one was above 30. Compared with the controls, lipid profiles of GX group showed significantly lower HDL-cholesterol (48.8 +/- 12.3 vs 62.9 +/- 40.5, P = 0.028) and higher LDL-cholesterol (112.9 +/- 29.9 vs 95.9 +/- 22.4, P = 0.032). The level of total serum cholesterol, triglyceride and the existence of dyslipoproteinemia were not related to the presence of GX. However, GX showed a close relationship with endoscopically determined atrophic gastritis and histologic severity (24/53, 44.4% vs 8/54, 14.8%, P = 0.0082). H pylori infection and bile reflux gastritis were not significantly related with GX. CONCLUSION: The prevalence of GX is 7% and it may be an increasing entity in Korea. Moreover, dyslipidemia and atrophic gastritis are found to be related to GX, but H pylori infection is not. PMID- 17729414 TI - Prevalence of overweightedness in patients with gastro-esophageal reflux. AB - AIM: To evaluate whether the prevalence of overweight and obese conditions is increased in gastro-esophageal reflux disease (GERD) patients (with 24-h pathological pH recordings) in comparison to general population. METHODS: A total of 196 consecutive patients (103 females, age range 18-83 years) with symptoms of gastro-esophageal reflux (GER) and 24-h pathological esophageal pH-metry. Body mass index (BMI) of the patients was calculated and its distribution (%) was compared with that of the Italian general population as assessed by National Bureau of Census (ISTAT). To evaluate the association of GERD with weight categories, the binomial test was employed. P < 0.05 was considered statistically significant. RESULTS: In males, overweightedness (BMI 25-25.9) was present in 43% of GERD patients vs 41.8% of Italian population (IP) (ns), obesity (BMI > or = 30) in 10.9% vs 9.1% (ns). In females overweight was present in 34.9% of GERD patients vs 25.7% of IP (P < 0.01), obesity in 13.6% of GERD patients vs 9.1% of IP (P < 0.01). No statistically significant differences were noted in different age classes. CONCLUSION: In comparison to the Italian general population, the prevalence of overweightedness and obesity is increased in female but not in male patients with ascertained gastro-esophageal reflux disease. PMID- 17729415 TI - Internal biliary fistula due to cholelithiasis: a single-centre experience. AB - AIM: To discuss about the perioperative problems encountered in patients with internal biliary fistula (IBF) caused by cholelithiasis. METHODS: In our hospital, 4,130 cholecystectomies were carried out for symptomatic cholelithiasis from January 2000 to March 2004 and only 12 patients were diagnosed with IBF. The perioperative data of these 12 IBF patients were analyzed retrospectively. RESULTS: The incidence of IBF due to cholelithiasis was nearly 0.3%. The mean age was 57 years. Most of the patients presented with non-specific complaints. Only two patients were considered to have IBF when gallstone ileus was observed during the investigations. Nine patients underwent emergency laparotomy with a pre operative diagnosis of acute abdomen. In the remaining three patients, elective laparoscopic cholecystectomy was converted to open surgery after identification of IBF. Ten patients had cholecystoduodenal fistula and two patients had cholecystocholedochal fistula. The mean hospital stay was 13 d. Two wound infections, three bile leakages and three mortalities were observed. CONCLUSION: Cholecystectomy has to be performed in early stage in the patients who were diagnosed as cholelithiasis to prevent the complications like IBF which is seen rarely. Suspicion of IBF should be kept in mind, especially in the case of difficult dissection during cholecystectomy and attention should be paid in order to prevent iatrogenic injuries. PMID- 17729416 TI - Evidence for the role of gastric mucosa at the secretion of soluble triggering receptor expressed on myeloid cells (strem-1) in peptic ulcer disease. AB - AIM: To investigate the role of gastric mucosa at the secretion of sTREM-1 in peptic ulcer. METHODS: Seventy two patients were enrolled; 35 with duodenal, 21 with gastric ulcer and 16 with chronic gastritis. Patients were endoscoped and gastric juice was aspirated. Patients with duodenal and gastric ulcer underwent a second endoscopy post-treatment. Biopsies were incubated in the absence/presence of endotoxins or gastric juice. Supernatants were collected and sTREM-1 and TNFalpha were measured by enzyme immunoabsorbent assays. Scoring of gastritis was performed before and after treatment according to updated Sydney score. RESULTS: Patients with duodenal and gastric ulcer and those with chronic gastritis had similar scores of gastritis. sTREM-1 was higher in supernatants of tissue samples of H pylori-positive than of H pylori-negative patients with gastric ulcer. Median (+/- SE) sTREM-1 was found increased in supernatants of patients with gastric ulcer before treatment (203.21 +/- 88.91 pg/1000 cells) compared to supernatants either from the same patients post-treatment (8.23 +/- 5.79 pg/1000 cells) or from patients with chronic gastritis (6.21 +/- 0.71 pg/1000 cells) (P < 0.001 and < 0.001, respectively). Similar differences for sTREM-1 were recorded among LPS-stimulated tissue samples of patients (P = 0.001). Similar differences were not found for TNFalpha. Positive correlations were found between sTREM-1 of supernatants from patients with both duodenal and gastric ulcer before treatment and the degree of infiltration of neutrophils and monocytes. CONCLUSION: sTREM-1 secreted by the gastric mucosa is an independent mechanism connected to the pathogenesis of peptic ulcer. sTREM-1 was released at the presence of H pylori from the inflamed gastric mucosa in the field of gastric ulcer. PMID- 17729417 TI - Inhibition of angiogenesis and HCT-116 xenograft tumor growth in mice by kallistatin. AB - AIM: To investigate the inhibitory effect of kallistatin (KAL) on angiogenesis and HCT-116 xenograft tumor growth. METHODS: Heterotopic tumors were induced by subcutaneous injection of 2 multiply 10(6) HCT-11 cells in mice. Seven days later, 2 multiply 10(11) rAAV-GFP or rAAV-KAL was injected intratumorally (n = 5 for each group). The mice were sacrificed at d 28, by which time the tumors in the rAAV-GFP group had grown to beyond 5% of the total body weight. Tumor growth was measured by calipers in two dimensions. Tumor angiogenesis was determined with tumor microvessel density (MVD) by immunohistology. Tumor cell proliferation was assessed by Ki-67 staining. RESULTS: Intratumor injection of rAAV-KAL inhibited tumor growth in the treatment group by 78% (171 +/- 52 mm(3)) at d 21 after virus infection compared to the control group (776 +/- 241 mm(3)). Microvessel density was significantly inhibited in tumor tissues treated with rAAV-KAL. rAAV-KAL also decreased the proportion of proliferating cells (Ki-67 positive cells) in tumors compared with the control group. CONCLUSION: rAAV mediated expression of KAL inhibits the growth of colon cancer by reducing angiogenesis and proliferation of tumor cells, and may provide a promising anti angiogenesis-based approach to the treatment of metastatic colorectal cancer. PMID- 17729418 TI - Changes in gene-expression profiles of colon carcinoma cells induced by wild type K-ras2. AB - AIM: To further elucidate the possible molecular biological activity of wild type K-ras2 gene by detecting changes in wild type K-ras2 gene-induced gene-expression profiles of colon carcinoma cells using cDNA microarray techniques. METHODS: Total RNA was isolated from peripheral blood of health volunteers. Reverse transcription of RNA and polymerase chain reaction were used to synthesize wild type K-ras2 cDNA. K-ras2 cDNA fragment was cloned into a T easy vector and sequenced. A eukaryotic expression vector pCI-neo-K-ras2 was constructed and transfected to Caco2 cell line using the liposome method. Finally, mRNA was isolated, reverse-transcribed to cDNA from pCI-neo-K-ras2 or pCI-neo blank vector transfected Caco cells, and analyzed by cDNA microarray assay. RESULTS: Restriction enzyme analysis and DNA sequencing verified that the constructed expression vector was accurate. High-quality RNA was extracted and reverse transcribed to cDNA for microarray assay. Among the 135 genes, the expression was up-regulated in 24 and down-regulated in 121. All these differentially expressed genes were related to cell proliferation, differentiation, apoptosis and signal transduction. CONCLUSION: Differentially expressed genes can be successfully screened from wild type K-ras2-transfected colon carcinoma cells using microarray techniques. The results of our study suggest that wild type K-ras2 is related to the negative regulation of cell proliferation, metabolism and transcriptional control, and provide new clues to the further elucidation of its possible biological activity. PMID- 17729419 TI - Matrix metalloproteinase-9-1562C>T polymorphism may increase the risk of lymphatic metastasis of colorectal cancer. AB - AIM: To explore the role of the matrix metalloproteinase-9 (MMP-9) polymorphism in colorectal cancer (CRC) in a northeast Chinese population. METHODS: Genotyping of MMP-9-1562C>T and 279R>Q polymorphisms was carried out on blood samples from 137 colorectal cancer patients and 199 controls using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Multivariate logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: The distribution of MMP-9 -1562C>T and 279 R>Q genotype was not significantly associated with the risk of CRC. However, the risk of llymph node metastasis of CRC was increased in patients with the 1562T allele (OR = 2.601; 95% CI = 1.160-5.835; P = 0.022). The frequency of MMP 9 279RR + RQ genotype was higher than the QQ genotype among CRC patients younger than sixty years old (OR = 0.102; 95% CI = 0.013-0.812; P = 0.012). CONCLUSION: Our results indicated that the MMP-9-1562C>T polymorphism affects lymph node metastasis of CRC. In addition, the MMP-9 279R allele may lead to a younger age of onset of colorectal cancer. PMID- 17729421 TI - Postoperative complications in patients with portal vein thrombosis after liver transplantation: evaluation with Doppler ultrasonography. AB - AIM: To study the postoperative complications in patients with preoperative portal vein thrombosis (PVT) undergoing liver transplantation (LT) and to evaluate the complications with Doppler ultrasonography. METHODS: Retrospective studies were performed on 284 patients undergoing LT (286 LT) with respect to pre and postoperative clinical data and Doppler ultrasonography. According to the presence and grade of preoperative PVT, 286 LTs were divided into three groups: complete PVT (c-PVT), partial PVT (p-PVT) and non-PVT, with 22, 30 and 234 LTs, respectively. Analyses were carried out to compare the incidence of early postoperative complications. RESULTS: PVT, inferior vena cava (IVC) thrombosis, hepatic artery thrombosis (HAT) and biliary complications were found postoperatively. All complications were detected by routine Doppler ultrasonography and diagnoses made by ultrasound were confirmed by clinical data or/and other imaging studies. Nine out of 286 LTs had postoperative PVT. The incidence of the c-PVT group was 22.7%, which was higher than that of the p-PVT group (3.3%, P < 0.05) and non-PVT group (1.3%, P < 0.005). No difference was found between the p-PVT and non-PVT groups (P > 0.25). Of the 9 cases with postoperative PVT, recanalizations were achieved in 7 cases after anticoagulation under the guidance of ultrasound, 1 case received portal vein thrombectomy and 1 case died of acute injection. Ten LTs had postoperative IVC thrombosis. The c-PVT group had a higher incidence of IVC thrombosis than the non-PVT group (9.1% vs 2.6%, P < 0.05); no significant difference was found between either the c-PVT and p-PVT groups (9.1% vs 6.7%, P > 0.5) or between the p-PVT and non-PVT groups (P > 0.25). Nine cases with IVC thrombosis were cured by anticoagulation under the guidance of ultrasound, and 1 case gained natural cure without any medical treatment after 2 mo. HAT was found in 2 non-PVT cases, giving a rate of 0.7% among 286 LTs. Biliary complications were seen in 12 LTs. The incidence of biliary complications in the c-PVT, p-PVT and non-PVT groups was 9.1%, 3.3% and 4.3%, respectively (P > 0.25 for all), among which 2 stenosis led retransplantations and others were controlled by relative therapy. CONCLUSION: C PVT patients tend to have a higher incidence of PVT and IVC thrombosis than non PVT patients after LT. The incidence of postoperative complications in p-PVT patients does not differ from that of non-PVT patients. A relatively low incidence of HAT was seen in our study. Doppler ultrasonography is a convenient and efficient method for detecting posttransplant complications and plays an important role in guiding treatment. PMID- 17729420 TI - Molecular evolution of hepatitis A virus in a human diploid cell line. AB - AIM: To investigate the hotspots, direction, and the time course of evolution of hepatitis A virus in the process of consecutive cell culture passage in human KMB17 diploid cells. METHODS: Wild type hepatitis A virus H2w was serially propagated in KMB17 cells until passage 30, and the full-length genomes of H2w and its six chosen progenies were determined by directly sequencing RT-PCR products amplified from viral genomic RNA. Alignment comparison of sequences from H2w with its six progenies and phylogenetic analysis of the whole VP1 region from H2w, progenies of H2w, and other cell culture adapted hepatitis A virus were then carried out to obtain data on the molecular evolution of hepatitis A virus in the process of consecutive passage in KMB17 cells. RESULTS: Most of the mutations occurred by passage 5 and several hotspots related to adaptation of the virus during cell growth were observed. After that stage, few additional mutations occurred through the remaining duration of passage in KMB17 cells except for mutation in the virulence determinants, which occurred in the vicinity of passage 15. The phylogenetic analysis of the whole VP1 region suggested that the progenies of H2w evolved closely to other cell culture adapted hepatitis A virus, i.e. MBB, L-A-1, other than its progenitor H2w. CONCLUSION: Hepatitis A virus served as a useful model for studying molecular evolution of viruses in a given environment. The information obtained in this study may provide assistance in cultivating the next generation of a seed virus for live hepatitis A vaccine production. PMID- 17729422 TI - Effects of lamivudine on the function of dendritic cells derived from patients with chronic hepatitis B virus infection. AB - AIM: To investigate if the nucleoside analogue lamivudine (LAM), a potent inhibitor of HBV replication, could restore the function of dendritic cells derived from patients with chronic hepatitis B (CHB) in an Asian population. METHODS: Dendritic cells (DCs) derived from mononuclearcytes of patients with chronic HBV infection were cultured in the presence of IL-4, granulocyte macrophage colony-stimulating factors (GM-CSF) and gradient concentrations of LAM (0-2 mmol/L). Cell morphology was observed under light microscopy. Cell surface molecules, including HLA-DR, CD80, CD83, and CD1alpha, were analyzed with flow cytometry. The concentrations of IL-6 and IL-12 in the supernatant were assayed by ELISA. T cell proliferation was assayed by methyl thiazolyl tetrazolium (MTT). RESULTS: The expression of CD1alpha on DC treated with 0.5 mmol/L LAM (LAM-DC 0.5 mmol/L) was significantly higher than that of DC untreated with LAM (54.1 +/- 4.21 vs 33.57 +/- 3.14, P < 0.05), and so was the expression of CD83 (20.24 +/- 2.51 vs 12.83 +/- 2.12, P < 0.05) as well as the expression of HLA-DR (74.5 +/- 5.16 vs 52.8 +/- 2.51, P < 0.05). Compared with control group, LAM-DC group (0.5 mmol/L) secreted significantly more IL-12 (910 +/- 91.5 vs 268 +/- 34.3 pg/mL, P < 0.05), had lower levels of IL-6 in the culture supernatant (28 +/- 2.6 vs 55 +/ 7.36 pg/mL, P < 0.05), markedly enhanced the stimulatory capacity in the allogeneic mixed leukocyte reaction (MLR) (1.87 +/- 0.6 vs 1.24 +/- 0.51, P < 0.05). CONCLUSION: The lower expression of phenotypic molecules and impaired allogeneic mixed lymphocyte reaction function of dendritic cells derived from patients with HBV infection could be restored in vitro by incubation with LAM. PMID- 17729423 TI - Alcohol binging causes peliosis hepatis during azathioprine therapy in Crohn's disease. AB - Patients with inflammatory bowel disease have normal life expectancy and, due to modern immunosuppressive therapies, also a normal quality of life. Since mostly young people are affected, their social behaviour suits this environment. Alcohol binging is an increasingly disturbing factor among young people. We describe a patient with Crohn's disease, treated with azathioprine, who developed peliosis hepatis after three epsiodes of alcohol binging. Liver toxicity was not observed previously during the course of the treatment. Azathioprine-induced peliosis hepatis is thought to be idiosyncratic in humans. From animal studies, however, it is clear that hepatic depletion of glutathione leads to azathioprine toxicity to the sinusoidal endothelial cells. Damage of these cells causes peliosis hepatis. Since alcohol binging leads to hepatic glutathione depletion, we conclude that in our patient the episodes of binging have reduced liver gluathione content and therefore this has increased azathioprine toxicity causing peliosis hepatis. The problem of alcohol binging has not yet been addressed in IBD patients undertaking immunosuppressive therapy. This should be reviewed in future considerations regarding patients advice. PMID- 17729424 TI - Watery diarrhea, hypokalemia and achlorhydria syndrome due to an adrenal pheochromocytoma. AB - Watery diarrhea, hypokalemia and achlorhydria (WDHA) syndrome caused by vasoactive intestinal polypeptide (VIP) -producing tumor only rarely occurs in patients with nonpancreatic disease. A 49-year-old woman was referred for evaluation of a right adrenal tumor incidentally diagnosed by abdominal ultrasound during the investigation of chronic watery diarrhea. Laboratory findings showed hypokalemia and excessive production of VIP and catecholamines. After surgical resection of the tumor, diarrhea subsided and both electrolytes and affected hormone levels normalized. Immunohistochemical examination confirmed a diagnosis of pheochromocytoma, which contained VIP-positive ganglion-like cells. We herein present the clinical and histogenetic implications of this rare clinical entity, with literature review. PMID- 17729425 TI - Eosinophilic gastroenteritis with cytomegalovirus infection in an immunocompetent child. AB - A 3-year-old boy developed transient protein-losing gastroenteropathy associated with cytomegalovirus (CMV) infection. Both IgG and IgM antibodies to CMV were positive in a serologic blood test. Upper gastrointestinal endoscopy showed multiple erosions throughout the body of the stomach, without enlarged gastric folds. Histological examination of the biopsy specimens indicated eosinophilic gastroenteritis and CMV infection. The patient had complete resolution without specific therapy for CMV in four weeks. An allergic reaction as well as CMV infection played important roles in the pathogenesis of this case. PMID- 17729427 TI - Surveillance colonoscopy practice in Lynch syndrome in the Netherlands: A nationwide survey. AB - Lynch syndrome, or hereditary nonpolyposis colorectal cancer (HNPCC), is the most common genetic disorder predisposing to colorectal cancer. As regular colonoscopic surveillance has been shown to reduce the incidence of colorectal cancer, this strategy is recommended worldwide. Recently, several advances in colonoscopic techniques have improved detection rates of neoplasia in Lynch syndrome. In this nationwide survey, we evaluated current surveillance colonoscopy practices for Lynch syndrome in the Netherlands and the extent to which advanced techniques have been adopted in routine clinical practice. PMID- 17729426 TI - Multiple intrahepatic pseudocysts in acute pancreatitis. AB - Liver pseudocysts are a very rare complication in acute pancreatitis with only a few cases previously described. The lack of experience and literature on this condition leads to difficulties in the differential diagnosis and management. We report herein a case of acute pancreatitis who developed multiple intrahepatic pseudocysts. After complete imaging evaluation, the diagnosis was still unclear and the patient was operated on. The presence of liver lesions in patients with acute pancreatitis should raise the possibility of intrahepatic pseudocysts. PMID- 17729428 TI - Obituary: professor Seturo Ebashi 1922-2006 - the discovery of troponin and forty years of its impact. PMID- 17729429 TI - Kairomones extracted from rice yellow stem borer and their influence on egg parasitization by Trichogramma japonicum ashmead. PMID- 17729430 TI - [HPV vaccination]. PMID- 17729431 TI - Current awareness in NMR in biomedicine. PMID- 17729432 TI - [Lyme borreliosis in children. Epidemiology, diagnosis, clinical treatment, and therapy]. AB - In Europe, Lyme borreliosis is the most common disease communicated by ticks and especially affects the skin, nervous system, joints, and heart. It is caused by at least four species of the spirochete Borrelia burgdorferi. The various pathologies are classified as early forms (erythema migrans, borrelia lymphocytom, early neuroborreliosis, carditis) or late forms (arthritis, acrodermatitis chronica atrophicans, chronic neuroborreliosis). The accuracy of serodiagnosis is 20-50% with erythema migrans, 70-90% with early neuroborreliosis, and nearly 100% with Lyme arthritis. Following special indications, the agent is confirmed by skin biopsy or spinal or joint puncture. Oral therapy is performed with amoxicillin, doxycycline, and cefuroxime, and intravenous therapy uses ceftriaxone, cefotaxime, or penicillin G. All in all, the prognosis of treated Lyme borreliosis is good. In childhood permanent defects are extremely rare, even following long-term manifestation at an early age. PMID- 17729433 TI - [Periinterventional prophylactic antibiotics in radiological port catheter implantation]. AB - PURPOSE: To evaluate whether catheter-related infections after radiologically placed port catheters can be reduced by single-shot periinterventional antibiosis. MATERIALS AND METHOD: Between January and September 2002, 164 consecutive patients with indication for central venous port catheter implantation were included in the present study. During implantation the interventional radiologist was responsible for deciding whether to administer a prophylactic single-shot antibiosis. The prophylactic antibiosis entailed intravenous administration of ampicillin and sulbactam (3 g Unacid, Pfizer) or 100 mg ciprofloxacine (Ciprobay, Bayer) in the case of an allergy history to penicillins. Catheter-related infection was defined as a local or systemic infection necessitating port catheter extraction. RESULTS: Indication for port catheter implantation was a malignant disease requiring chemotherapy in 158 cases. The port catheter (Chemosite [Tyco Healthcare] [n = 123], low-profile [Arrow International] [n = 35], other port system [n = 6]) was implanted via sonographically guided puncture of the right jugular vein in 139 patients, via the left jugular vein in 24 cases and via the right subclavian vein in one patient. 75 patients received periinterventional prophylactic antibiosis (Unacid [n = 63] Ciprobay [n = 12]) and 89 patients did not receive antibiosis. The prophylactic antibiosis caused a minor allergic reaction in one patient that improved with antihistamic and corticoid medication. A total of 7 ports, 6 without prophylactic antibiosis versus one with periinterventional prophylaxis, were extracted due to infectious complications. CONCLUSION: Single-shot periinterventional prophylactic antibiosis can reduce early and late infectious complications after radiological-interventional placement of central venous port catheters. PMID- 17729434 TI - Current awareness in prenatal diagnosis. PMID- 17729435 TI - Joy of rapid responses. Don't take points raised in open and free discussion personally. PMID- 17729436 TI - Joy of rapid responses. Rapid responses are useful... PMID- 17729437 TI - Joy of rapid responses. Rapid responses are useful...but perhaps not entirely effective. PMID- 17729438 TI - Joy of rapid responses. Summary of responses. PMID- 17729439 TI - Mathematicians and science. PMID- 17729440 TI - Role of megalin and cubilin in renal physiology and pathophysiology. AB - Megalin and cubilin are endocytic receptors highly expressed in the endocytic apparatus of the renal proximal tubule. These receptors appear to be responsible for the tubular clearance of most proteins filtered in the glomeruli. Cubilin is a peripheral membrane protein, and therefore it does not have an endocytosis signaling sequence. It appears that megalin is responsible for internalization of cubilin and its ligands in addition to internalizing its own ligands. The proteinuria observed in megalin-deficient mice, in dogs lacking functional cubilin, and in patients with distinct mutations of the cubilin gene illustrates the importance of the receptors. PMID- 17729441 TI - CLC chloride channels and transporters: a biophysical and physiological perspective. AB - Chloride-transporting proteins play fundamental roles in many tissues in the plasma membrane as well as in intracellular membranes. They have received increasing attention in the last years because crucial, and often unexpected and novel, physiological functions have been disclosed with gene-targeting approaches, X-ray crystallography, and biophysical analysis. CLC proteins form a gene family that comprises nine members in mammals, at least four of which are involved in human genetic diseases. The X-ray structure of the bacterial CLC homolog, ClC-ec1, revealed a complex fold and confirmed the anticipated homodimeric double-barreled architecture of CLC-proteins with two separate Cl-ion transport pathways, one in each subunit. Four of the mammalian CLC proteins, ClC 1, ClC-2, ClC-Ka, and ClC-Kb, are chloride ion channels that fulfill their functional roles-stabilization of the membrane potential, transepithelial salt transport, and ion homeostasisin the plasma membrane. The other five CLC proteins are predominantly expressed in intracellular organelles like endosomes and lysosomes, where they are probably important for a proper luminal acidification, in concert with the V-type H+-ATPase. Surprisingly, ClC-4, ClC-5, and probably also ClC-3, are not Cl- ion channels but exhibit significant Cl-/H+ antiporter activity, as does the bacterial homolog ClC-ec1 and the plant homolog AtCLCa. The physiological significance of the Cl-/H+ antiport activity remains to be established. PMID- 17729442 TI - Physiology of epithelial Ca2+ and Mg2+ transport. AB - Ca2+ and Mg2+ are essential ions in a wide variety of cellular processes and form a major constituent of bone. It is, therefore, essential that the balance of these ions is strictly maintained. In the last decade, major breakthrough discoveries have vastly expanded our knowledge of the mechanisms underlying epithelial Ca2+ and Mg2+ transport. The genetic defects underlying various disorders with altered Ca2+ and/or Mg2+ handling have been determined. Recently, this yielded the molecular identification of TRPM6 as the gatekeeper of epithelial Mg2+ transport. Furthermore, expression cloning strategies have elucidated two novel members of the transient receptor potential family, TRPV5 and TRPV6, as pivotal ion channels determining transcellular Ca2+ transport. These two channels are regulated by a variety of factors, some historically strongly linked to Ca2+ homeostasis, others identified in a more serendipitous manner. Herein we review the processes of epithelial Ca2+ and Mg2+ transport, the molecular mechanisms involved, and the various forms of regulation. PMID- 17729443 TI - IFSSH Flexor Tendon Committee Report 2007. PMID- 17729444 TI - [Analysis of morbidity in vicinity of a tungsten-molybdenum industrial complex]. AB - Morbidity rates were analyzed in adults residing in vicinity of a tungsten molybdenum industrial complex. The structure of morbidity was examined in relation to the physiological role of a number of heavy metals that are the priority contaminants in this area and with the habits of the residential population. The incidence of diseases of the musculoskeletal system, connective tissue, and respiratory organs was significantly higher in the area adjacent to the complex. In the mid-highlands, there are low incidence rates of circulatory, digestive, and urogenital diseases, and neoplasms as compared with the republican rates. PMID- 17729445 TI - [Medical examinations of children in poor environmental areas]. PMID- 17729446 TI - [Accumulation of heavy metals in cereal crops and ways of reducing their levels]. AB - The study deals with the levels of heavy metals in the raw grain grown in the agricultural lands of the Oryol Region and provides the results of a trial of a complex enzymatic agent based on phitase and succinic acid used to reduce the levels of heavy levels in the wheat and rye grains during manufacture of grain bread. The use of the complex-acting enzymatic agent based on phitase obtained from the fungus Penicillium canescens in combination with 0.1% succinic acid of the mass of wheat and rye grains when the latter is prepared for the manufacture of grain bread has been established to reduce the concentrations of nickel, lead, cadmium, and chromium, by lowering the levels of MAFAM, spore-forming bacteria, moulds, and yeasts in the raw materials. PMID- 17729447 TI - [Sanitary and epidemiological well-being in children and adolescents: state-of the-art and ways of solving the problem]. AB - In the children and adolescents of the Russian Federation, there is an increase in the incidence of a number of nosological entities, a significant prevalence of chronic diseases, and a reduction in health quality in children. According to the statistical data, in the past 5 years, the overall incidence has increased by 16% in children (aged 0-14 years) (171268 per 100,000 children in 2005) by 18% in adolescents. The incidence of diseases of blood and blood-forming organs, anemias, as well diseases of the respiratory, urogenital, and nervous systems, and congenital anomalies continues to increase. Along with socioeconomic causes, this is all due to the negative influence of environmental factors, dietary defects, and, in some cases, poor upbringing and teaching conditions, which do not comply with the hygienic standards and sanitary rules. Under the established conditions, the maintenance and improvement of children's health is the most important state task, the provision of their sanitary and epidemiological welfare being one of the major constituents in its accomplishment. In the past 3 years, the principal state sanitary inspector has issued 17 regulations on different aspects of the sanitary and epidemiological well-being of children and adolescents. The preparation of the draft "National Program for the Prevention of Adverse Health Influence of Environmental Factors for the Sake of the Future of Children and Adolescents for 2007-2010" has been currently completed. The Group of Eight Summit has noted that resolute opposition to threats of infectious diseases, the leading cause of death in the world, is vital to the global development and welfare of mankind. It has adopted the resolution that it is essential to make specific achievements in the strengthening international cooperation in the surveillance and monitoring of infectious diseases; to intensify researches; to second the efforts of appropriate international organizations, which are aimed at effectively opposing the outbreaks of avian influenza, and to prepare for a possible pandemic; to intensify measures against HIV/AIDS, tuberculosis, and malaria; to make the prevention and treatment of infectious diseases more accessible to the population; to avert and eliminate the epidemic consequences of natural disasters and man-caused catastrophes. Moreover, Russia has taken a number of obligations to finance appropriate programs. Of particular importance is the implementation of the Priority National Health Project involving additional immunization of the population and primarily children against viral hepatitis B (VHB), rubella, influenza, and poliomyelitis. This year, 4.1 billion rubles has been allocated within the framework of the priority national project for the purchase of vaccines to immunize 10 million children and adolescents against VHB, 5 million children against rubella, 150 thousand children against poliomyelitis with inactivated vaccine, 22 million individuals, including children going to preschool facilities and lst-4th-form pupils, against influenza. The guidelines for action aimed at providing the sanitary and epidemiological well-being of the population, may include as follows: to further improve the normative and methodical bases; to complete the development of the draft "The Principles in the Policy of State in the Healthy Nutrition of the Russian Federation' Population for 2007-2010", "National Program for the Prevention of Adverse Health Influence of Environmental Factors for the Sake of the Future of Children and Adolescents for 2007-2010" and submit them to the Government of the Russian Federation for approval; to introduce preventive educational programs into the general educational establishments in order to mould in children and adolescents healthy lifestyle habits, a conscientious attitude towards to the health of theirs' and those around them. PMID- 17729448 TI - [The use of learning computers in the general educational system: hygienic aspects]. AB - The use of learning computers (LCs) in a present-day academic process poses for hygienists and physiologists new problems, such as to evaluate the influence of LCs on schoolchildren's health and to substantiate and to develop the ways of drawing up and presenting the materials in terms of their readability and regulation of learning regimens. Analysis of the currently available LCs has established the factors contributing to the accelerated development of visual and overall fatigue, its accumulation: the brightness characteristics of electronic pages, including both the violation of the allowable brightness levels and the irregularity of intensity distribution; a significant inadequacy of type sizes; a great variety of lettering and coloring. The recent LCs for general education are the visual aggressive medium for schoolchildren, which is certain to require their hygienic evaluation on the basis of specially developed hygienic requirements for LCs. PMID- 17729449 TI - [The health status of children and adolescents and the demographic situation in the Republic of Tyva]. PMID- 17729450 TI - [Indoor air decontamination by the ionic wind technology]. PMID- 17729451 TI - [Inverse voltammetric determination of water chromium sociohygienic monitoring methodology and practice]. PMID- 17729452 TI - Low-back pain vexed by avascular necrosis of the femoral head. PMID- 17729453 TI - Closing the gap between animals and humans. PMID- 17729454 TI - [Tumors in the gallbladder: a possible differentiation between malignant and benign tumours]. PMID- 17729456 TI - SIR JOSEPH LARMOR AND MODERN MATHEMATICAL PHYSICS. PMID- 17729455 TI - [The use of antiviral agents during an (impending) influenza pandemic]. PMID- 17729458 TI - HARRISON ESTELL HOWE. PMID- 17729459 TI - COMMITTEE ON SANITARY ENGINEERING OF THE NATIONAL RESEARCH COUNCIL. PMID- 17729457 TI - WHAT MORE CAN ENGINEERING COLLEGES DO THROUGH ESMWT? PMID- 17729460 TI - JOINT COUNCIL OF SCIENTIFIC MEN IN GREAT BRITAIN. PMID- 17729461 TI - AWARDS OF THE AMERICAN SOCIETY OF CIVIL ENGINEERS. PMID- 17729462 TI - PRESENTATION OF THE MELCHETT MEDAL. PMID- 17729463 TI - CANCELLATION OF THE ANNUAL MEETING OF THE AMERICAN PHYSIOLOGICAL SOCIETY. PMID- 17729464 TI - THE AMERICAN INSTITUTE OF ELECTRICAL ENGINEERS. PMID- 17729465 TI - AGAR-BEARING SEAWEEDS AT LA JOLLA, CALIFORNIA. PMID- 17729466 TI - EARLY MASTERY OF THE GROUP CONCEPT. PMID- 17729467 TI - WHEAT GRAINS WITHOUT EMBRYOS. PMID- 17729468 TI - ABSTRACT OF A PLAN FOR COLLABORATION BETWEEN COLLEGES AND UNIVERSITIES AND THE DEPARTMENT OF AGRICULTURE WITH SPECIAL REFERENCE TO TRAINING REPLACEMENTS DURING THE WAR. PMID- 17729469 TI - CAROTENE. I. PRELIMINARY REPORT ON DIPHENYLAMINE AS A STABILIZER FOR CAROTENE. PMID- 17729470 TI - ISOMORPHISM AND ISOTYPISM AMONG SILICATES AND PHOSPHATES. PMID- 17729471 TI - EDEMA IN VITAMIN E DEFICIENT CHICKS. PMID- 17729472 TI - A DEVICE FOR CALIBRATING SMALL AIR PUMPS. PMID- 17729473 TI - THE LOGICAL BASIS OF THE SANITARY POLICY OF MOSQUITO REDUCTION. PMID- 17729475 TI - ISOLATION AND THE ORIGIN OF SPECIES. PMID- 17729474 TI - DR. O. F COOK'S 'SOCIAL ORGANIZATION AND BREEDING HABITS OF THE COTTON-PROTECTING KELEP OF GUATEMALA.'. PMID- 17729476 TI - THE SMALL MOUNDS OF THE UNITED STATES. PMID- 17729477 TI - THE LOCH LEVEN TROUT IN CALIFORNIA. PMID- 17729478 TI - THE RELATION OF SOIL TEXTURE TO APPLE PRODUCTION. PMID- 17729479 TI - A CORRECTION OF THE GENERIC NAME (DINOCHOEligRUS) GIVEN TO CERTAIN FOSSIL REMAINS FROM THE LOUP FORK MIOCENE OF NEBRASKA. PMID- 17729481 TI - BOTANICAL NOTES. PMID- 17729480 TI - NOTES ON ENTOMOLOGY. PMID- 17729482 TI - INTERNATIONAL EXPLORATION OF THE NORTH SEA. PMID- 17729484 TI - GREEK AT CAMBRIDGE. PMID- 17729483 TI - THE AMERICAN PSYCHOLOGICAL ASSOCIATION. PMID- 17729485 TI - How To Be Interesting Though Factual. PMID- 17729487 TI - News of Science. PMID- 17729486 TI - Yale Natural Radiocarbon Measurements III. PMID- 17729488 TI - Meetings and Societies. PMID- 17729489 TI - EQUIPMENT NEWS. PMID- 17729490 TI - THE LAWS OF HYDRAULIC DEGRADATION. PMID- 17729491 TI - COMMERCIAL GEOGRAPHY. PMID- 17729492 TI - ELECTRICAL SCIENCE. PMID- 17729493 TI - The Theory of the Origin of Species by Natural Selection. PMID- 17729494 TI - On Alleged Mongoloid Traits in the American Race: In Reply to Dr. Ten Kate. PMID- 17729495 TI - Answers. PMID- 17729496 TI - Buffalo on the Texas Plains. PMID- 17729497 TI - 'Bi-daily.'. PMID- 17729498 TI - SCIENCE NEWS. PMID- 17729500 TI - DOES THE "RADIO ACT" HAMPER RESEARCH? PMID- 17729499 TI - THE CONFUSION OF TONGUES. PMID- 17729501 TI - COFFEE AND CACAO IN SOUTHERN FLORIDA. PMID- 17729502 TI - IODINE IN GOITER TREATMENT. PMID- 17729503 TI - THE SIMILARITY BETWEEN THE MECHANISM OF THE RENNIN AND PECTASE (PECTIN METHOXYLASE) REACTIONS. PMID- 17729504 TI - GENETICS, SULFHYDRYL AND CANCER. PMID- 17729506 TI - KETENE (CH2=CO): A NEW REAGENT FOR THE DETOXIFICATION OF VACCINE. PMID- 17729505 TI - GROWTH IN HEIGHT AND WEIGHT IN COLLEGE AND UNIVERSITY WOMEN. PMID- 17729507 TI - THE OROGENIC HISTORY OF CENTRAL UTAH. PMID- 17729508 TI - PETROLEUM SPRAYS FOR DANDELIONS. PMID- 17729509 TI - AN APPARATUS FOR AUTOMATICALLY MAINTAINING REDUCED PRESSURE. PMID- 17729510 TI - COMMENT AND CRITICISM. PMID- 17729511 TI - Popular names of California flowers. PMID- 17729512 TI - A singular optical phenomenon. PMID- 17729513 TI - The cranial ribs of Micropterus. PMID- 17729514 TI - Pleuracanthus and Didymodus. PMID- 17729515 TI - The use of the method of rates in mathematical teaching. PMID- 17729516 TI - THE GOVERNMENT, AND ECONOMIC ENTOMOLOGY. PMID- 17729517 TI - RECENT GEOLOGICAL OBSERVATIONS IN THE CANADIAN NORTH-WEST TERRITORY. PMID- 17729518 TI - FIVE BRAZILIAN DIAMONDS. PMID- 17729519 TI - THE DISTRIBUTION OF COMETS WITH REFERENCE TO SOLAR MOTION. PMID- 17729520 TI - VOLCANIC SAND IVIIICH FELL AT UNALASHKA,ALASKA, OCT. 20, 1883, AND SOME CONSIDERATIONS CONCERNING ITS COMPOSITION. PMID- 17729521 TI - METEOROLOGICAL CHARTS OF THE NORTH ATLANTIC. PMID- 17729522 TI - INVERTEBRATES OF THE TALISMAN EXPEDITION. PMID- 17729524 TI - THOUAR AND CREVAUX. PMID- 17729523 TI - THE RELATION OF THE MOUND-BUILDERS TO THE HISTORIC INDIANS. PMID- 17729526 TI - COUES'S BIOGEN. PMID- 17729525 TI - ENCKE'S COMET, AND THE RESISTING MEDIUM. PMID- 17729527 TI - REPORT OF THE OBSERVATORY AT HERENY, HUNGARY. PMID- 17729529 TI - THE EXHIBITION OF FOSSIL VERTEBRATES. PMID- 17729528 TI - INTELLIGENCE FROM AMERICAN SCIENTIFIC STATIONS. PMID- 17729530 TI - MUSEUM METHODS. PMID- 17729531 TI - THE FLOW OF THE CONNECTICUT RIVER. PMID- 17729532 TI - AMERICAN AMBER-PRODUCING TREE. PMID- 17729533 TI - ZOOLOGICAL NOMENCLATURE--A PROPOSAL. PMID- 17729534 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17729535 TI - CURRENT NOTES ON PHYSIOGRAPHY. PMID- 17729536 TI - CERTITUDES AND ILLUSIONS. PMID- 17729537 TI - INSTINCT. PMID- 17729538 TI - VIVISECTION. PMID- 17729539 TI - FOOTGEAR. PMID- 17729540 TI - NATIONAL GEOGRAPHIC SOCIETY. PMID- 17729541 TI - GLACIAL PHENOMENA BETWEEN LAKE CHAMPLAIN, LAKE GEORGE AND HUDSON RIVER. PMID- 17729542 TI - THE EARLY SEGREGATION OF FRESHWATER TYPES. PMID- 17729543 TI - DRY DREDGING IN THE MISSISSIPPIAN SEA. PMID- 17729544 TI - ANTIDROMIC PROBLEMS. PMID- 17729545 TI - TYPHOID FEVER DISSEMINATED THROUGH THE MILK SUPPLY. PMID- 17729546 TI - ELEVENTH INTERNATIONAL CONGRESS OF AMERICANISTS. PMID- 17729547 TI - RECENT INVESTIGATIONS UPON THE EMBRYOLOGY AND PATHOLOGY OF TEETH. PMID- 17729548 TI - CURRENT NOTES ON PHYSIOGRAPHY. PMID- 17729549 TI - THE INVERTED IMAGE ON THE RETINA. PMID- 17729551 TI - SHELLS AS IMPLEMENTS. PMID- 17729552 TI - SCIENCE AND CYCLOPAeDIAS. PMID- 17729550 TI - A REPLY. PMID- 17729553 TI - Drug regulation. PMID- 17729554 TI - Drug regulation. PMID- 17729555 TI - Pluto's Neighbor. PMID- 17729557 TI - Scientific research and policy analysis. PMID- 17729556 TI - Smallpox eradication. PMID- 17729558 TI - Electrons in glass. PMID- 17729559 TI - Mission-oriented research for light machinery. AB - The time of intelligent machines is upon us. But the United States is not actively pursuing this rich field of technological development. This is evidenced by the U.S. trade deficit of $9 billion in this market in 1977. The synergistic approach of Japan, Germany, Russia, and other countries to research, development, and demonstration among government, academic, and industrial groups is paying big dividends in vital U.S. markets. This article outlines a specific solution in terms of a U.S. national research policy for light machinery and robotics. PMID- 17729560 TI - Year of the grasshopper keeps EPA on the hop. PMID- 17729561 TI - For the eleemosynary elite and others, a new magazine. PMID- 17729562 TI - Some Insights from Inside in NSB Report on Research. PMID- 17729563 TI - NSA Slaps Secrecy Order on Inventors' Communications Patent. PMID- 17729565 TI - Population biology: bicentennial assessment. PMID- 17729564 TI - The science and politics of a disinvitation. PMID- 17729567 TI - Genetic apparatus. PMID- 17729566 TI - Phenomenology of perception. PMID- 17729568 TI - Carbon-13 depletion in a subalpine lake: carbon flow implications. AB - Plankton (larger than 76 micrometers) taken from an undisturbed oligotrophic was found to have delta(13)C values (=(13)/(12)C relative to the Pee Dee be- belemnite standard) rangingfrom -44 to -47 per mil. This extraordinary (13)C depletion, together with characteristics of the inorganic carbon pool, indicates that lake respiration as well as surrounding soil respiration provide important carbon sources for plankton production in this lake. PMID- 17729569 TI - Energy balance for ethyl alcohol production from crops. AB - Energy requirements to produce ethyl alcohol from three different crops in Brazil (sugarcane, cassava, and sweet sorghum) were calculated. Figures are presented for the agricultural and industrial phases. The industrial phase is always more energy-intensive, consuming from 60 to 75 percent of the total energy. Sugarcane is the more efficient crop for ethyl alcohol production, followed by sweet sorghum and cassava from a net energy viewpoint. The utilization of sweet sorghum stems might increase the total energy gain from this crop to almost the same level as sugarcane. Cassava has a lower energy gain at the present state of agriculture in Brazil. PMID- 17729570 TI - Carbon isotopic evidence for different feeding patterns in two hyrax species occupying the same habitat. AB - The carbon-13/carbon-12 ratios of the carbonate and collagen fractions of bone of the sympatric hyrax species Procavia johnstoni and Heterohyrax brucei indicate that the former obtains most of its diet by grazing while the latter is primarily a browser. The carbon-13/carbon-12 ratios of these fractions in fossil bone will record information about diet if they have not been altered during diagenesis. PMID- 17729571 TI - Early archeological evidence for shellfish collecting. AB - Geologic evidence, supported by infinite carbon-14 dates and Middle Stone Age cultural associations, indicates that two open-air shell middens recently found at Sea Harvest and Hoedjies Punt, Saldanha Bay, South Africa, date from the terminal part of the Last Interglacial, about 70,000 to 60,000 years ago. These middens are among the oldest known records for systematic human exploitation of marine resources anywhere in the world. The faunal contents of the middens suggest that the Middle Stone Age people who accumulated them utilized marine resources less intensively than their Later Stone Age successors in similar coastal settings. PMID- 17729572 TI - Chemoreceptors in lepidoptera: stereochemical differentiation of dual receptors for an achiral pheromone. AB - The racemate and optically pure enantiomers of 9-(2-cyclopenten-1yl)nonyl acetate have been synthesized and shown to mimic certain biological properties of (Z)-11 tetradecenyl acetate. European corn borers and red-banded leaf rollers respond differently to the racemate and to the enantiomers in precopulatory behavior bioassay. The responses demonstrate the presence of two stereospecific chemoreceptors, show the chiral character of these receptors, and define the conformation of carbon atoms 10 to 14 of (Z)-11-tetradecenyl acetate in these receptors. PMID- 17729573 TI - Social Inhibition of Maturation in Natural Populations of Xiphophorus variatus (Pisces: Poeciliidae). AB - According to analyses of field samples, social inhibition of maturation is at work in natural populations of the variable platyfish, Xiphophorus variatus. In the laboratory, adult males inhibit the maturation of juveniles; the inhibition is overcome as the juveniles increase in size. The proportion of maturing males in any field collection is related to the number of adult males present and the size of the juveniles. The more adults, the fewer maturing males are present; the larger the average juvenile, the greater the number of males maturing. The evolution of this system is best understood in terms of individual selection, but consequences of the system buffer the population against the effects of predation. PMID- 17729575 TI - Emission of maternal pheromone. PMID- 17729574 TI - Microgeographic prediction of polygyny in the lark bunting. AB - Field experiments on breeding populations of lark buntings (Calamospiza melanocorys) in South Dakota support the hypothesis that polygyny is promoted by a high variance in quality among male territories. Among these birds protection of the nest site from solar radiation is the major indicator of quality: nestling survival was significantly correlated with nest-site cover, and experimental increase of shading resulted in higher reproductive success. Males with superior territories attracted two mates, whereas those with poor territories failed to attract any. Secondary females had fledging success at least equal to that of contemporaneous monogamous pairs. On the sole basis of a shading score for each territory, the mating status of males (polygynous, monogamous, or bachelor) was predicted accurately in new areas of Colorado and North Dakota before females arrived. PMID- 17729576 TI - PRODUCTS and MATERIALS. PMID- 17729577 TI - THE NEW YORK BOTANIC GARDEN. PMID- 17729578 TI - THE SUBMERGENCE OF WESTERN EUROPE PRIOR TO THE NEOLITHIC PERIOD. PMID- 17729579 TI - THE GENERIC NAME OF THE WATER-WEED. PMID- 17729581 TI - CURRENT NOTES ON PHYSIOGRAPHY (XI.). PMID- 17729580 TI - CURRENT NOTES ON ANTHROPOLOGY (X.). PMID- 17729582 TI - PSYCHOLOGICAL NOTES (I.). PMID- 17729583 TI - ANCESTRY OF THE MAMMALIA. PMID- 17729584 TI - TOPOGRAPHIC METHODS. PMID- 17729585 TI - THE METEOROLOGICAL AND MAGNETICAL OBSERVATORY ZI-KA-WEI, NEAR SHANGHAI, CHINA. PMID- 17729586 TI - Lehrbuch der Biologie der Pflanzen. PMID- 17729587 TI - The Geological and Natural History Survey of Minnesota. The Twenty-third Annual Report, for the year 1894. N. H. WINCHELL, State Geologist. Minneapolis, Harrison & Smith, State Printers. 1895. 8vo. 255pp. PMID- 17729588 TI - FOLK-TALES. PMID- 17729589 TI - The Second Law of Thermodynamies. PROFESSOR OLIVER J. LODGE, Proceedings, Liverpool Engineering Society, December, 1894, twenty-first session, with discussion. PMID- 17729590 TI - SOME CHEMICAL BEARINGS OF PHARMACOLOGY. PMID- 17729592 TI - CHANGES IN LONGEVITY OF AMERICANS IN THE LAST DECADE. PMID- 17729591 TI - THE PRESENT SITUATION IN THE RADIUM INDUSTRY. PMID- 17729593 TI - THE OKLAHOMA-TEXAS BOUNDARY SUIT. PMID- 17729595 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17729594 TI - CHAUNCEY WILLIAM WAGGONER. PMID- 17729596 TI - AN EXCEPTIONALLY DARK DAY IN NEW YORK. PMID- 17729598 TI - THAT PLANT. PMID- 17729599 TI - "WHAT IS A PLANT?". PMID- 17729597 TI - THE MASS LAW AND STATISTICAL EQUILIBRIUM. PMID- 17729600 TI - "EROBIC". PMID- 17729601 TI - USE OF THE CARBON DIOXIDE FREEZING ATTACHMENT ON THE ROTARY MICROTOME. PMID- 17729602 TI - THE AMERICAN MATHEMATICAL SOCIETY. PMID- 17729603 TI - Letters to the editor. PMID- 17729604 TI - Latin america: bedeviled science. PMID- 17729605 TI - Defense of science. PMID- 17729606 TI - Esthetics of asymmetry. PMID- 17729607 TI - Letters to the editor. PMID- 17729608 TI - Man's First Route to America. PMID- 17729609 TI - Shift of NSF Funds. PMID- 17729610 TI - The next industrial revolution. PMID- 17729612 TI - Student unrest: sources and consequences. PMID- 17729611 TI - The atmosphere of jupiter. PMID- 17729614 TI - Strategic arms talks: what is negotiable? PMID- 17729615 TI - Education: A Show of Power over Funds for Innovation. PMID- 17729616 TI - FDA wins round in panalba fight. PMID- 17729618 TI - Structure of polywater. PMID- 17729617 TI - Polywater: polymer or artifact? AB - Several polywater samples were prepared by the standard methods and have the same physical and spectroscopic properties as those made in other laboratories. However, a variety of chemical analyses show high concentrations of impurities which may account for many of the anomalous properties. PMID- 17729619 TI - "Polywater": a hydrosol? AB - Measurements of the dielectric constant and the effective parallel conductance of a specimen of anomalous water suggest that anomalous water is a hydrosol consisting of finely divided particulate matter suspended in ordinary water. Scanning electron micrography confirms the presence of particulate matter. These new experimental data provide an alternative explanation for the properties of anomalous water. PMID- 17729620 TI - Alpha radioactivity of the lunar surface at the landing sites of surveyors 5,6, and 7. AB - Evidence has been obtained for a radioactive deposit on the lunar surface at Mare Tranquillitatis with a total intensity of 0.09 +/- 0.03 alpha disintegration per second per square centimeter. The presence of polonium-210 in amounts that are close to equilibrium indicates a continuous turnover rate of lunar material at this site of less than 0.1 micrometer per year. The lack of such a deposit at two other lunar sites suggests lower local concentrations of uranium there. PMID- 17729621 TI - Search for an effect of the sun on the frequency of 18-centimeter radiation. PMID- 17729622 TI - Sunglint patterns in satellite pictures. PMID- 17729623 TI - Mission to martian satellites. PMID- 17729624 TI - Errata for the moon issue (30 january 1970). PMID- 17729625 TI - A MATHEMATICAL THEORY OF EQUILIBRIUM WITH APPLICATIONS TO MINIMAL SURFACE THEORY. PMID- 17729626 TI - TECHNICAL PROGRESS IN AVIATION. PMID- 17729627 TI - PROFESSOR LAWRENCE AND THE DEVELOPMENT OF THE CYCLOTRON. PMID- 17729628 TI - WORK OF THE UNITED STATES GEOLOGICAL SURVEY. PMID- 17729630 TI - A PLAN TO PROMOTE CULTURAL FELLOWSHIP AND COOPERATION AMONG THE AMERICAN REPUBLICS. PMID- 17729629 TI - THE SIXTH LERNER-AMERICAN MUSEUM BIG GAME FISH EXPEDITION. PMID- 17729631 TI - THE NATIONAL RESEARCH FELLOWSHIP FOR WOMEN IN SCIENCE. PMID- 17729632 TI - THE GEOLOGICAL SOCIETY OF AMERICA. PMID- 17729633 TI - AN INVENTORY OF NATURAL VEGETATION TYPES AND THE NEED FOR THEIR PRESERVATION. PMID- 17729634 TI - LEADING NATIONS IN SCIENCE AND THE NOBEL PRIZE. PMID- 17729636 TI - SCIENTIFIC SOCIETIES IN WAR TIME. PMID- 17729635 TI - FESTSCHRIFT OF PROFESSOR EMBRIK STRAND. PMID- 17729637 TI - THE SOYBEAN CROP IN THE UNITED STATES. PMID- 17729638 TI - RED CELL VOLUME CIRCULATING AND TOTAL AS DETERMINED BY RADIO IRON. PMID- 17729639 TI - THE TURNOVER OF ACID-SOLUBLE PHOSPHORUS IN THE KIDNEYS OF RATS. PMID- 17729640 TI - AN INVERSE DISTANCE VARIATION FOR CERTAIN SOCIAL INFLUENCES. PMID- 17729641 TI - A STABLE TRYPSIN SOLUTION. PMID- 17729642 TI - PURIFICATION OF DIPHTHERIA ANTI-TOXIN. PMID- 17729643 TI - THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE PRINCIPLES OF PALEOGEOGRAPHY. PMID- 17729644 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17729646 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17729645 TI - A NATIONAL BUREAU OF SEISMOLOGY. PMID- 17729647 TI - EARLIER REFERENCES TO THE RELATION OF FLIES TO DISEASE. PMID- 17729648 TI - SCIENTIFIC JOURNALS AND ARTICLES. PMID- 17729649 TI - THE FORTY-FIRST GENERAL MEETING OF THE AMERICAN CHEMICAL SOCIETY. PMID- 17729650 TI - THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE SECTION K AT THE BOSTON MEETING. PMID- 17729651 TI - SECTION F. PMID- 17729652 TI - Scientific cooperation with Vietnam. PMID- 17729653 TI - Chemical coal cleaning. PMID- 17729654 TI - Juvenile-onset diabetes: significance of findings. PMID- 17729655 TI - Nuclear industry: safety record. PMID- 17729656 TI - Erratum. AB - In the issue of 22 June, in the News and Comment article, "Congress says bioassay reports are stalled" (p. 1288), Philippe Shubik is identified as the "former director" of the University of Nebraska's Eppley Institute for Research in Cancer. Shubik is in fact on leave from that post until 1 July 1980. Norman Cromwell has been named acting director while Shubik is on leave. PMID- 17729658 TI - Self-Care: A Nation's Best Health Insurance. PMID- 17729657 TI - Weather prediction. PMID- 17729659 TI - The origin of the elements. PMID- 17729661 TI - Solar Activist, Denis Hayes, Heads SERI. PMID- 17729662 TI - No move for weapons labs. PMID- 17729660 TI - Photosynthetic pathway and biomass energy production. AB - The current interest in locating new or alternative sources of energy has focused attention on solar energy capture by crops that can be subsequently utilized as a substitute for fossil fuels. The very high productivity of sugarepane and the fact that it accumulates sugars that are directly fermentable to alcohol may have caused seemingly less productive crops to be overlooked. We show here that recoverable alcohol from achievable commercial yields of pineapple can actually equal that of sugarcane, with the pineapple crop requiring only a fraction of the water used by sugarcane. Pineapple is well adapted to the subhumid or semiarid tropics and thus is particularly well suited for exploiting large areas not now under cultivation with any crop of commercial value. PMID- 17729664 TI - A blow for the whales. PMID- 17729663 TI - U.s. Rubber shrub may have hidden thorn. PMID- 17729665 TI - Run on risk and benefit. PMID- 17729667 TI - An oil insurance policy that may lapse. PMID- 17729666 TI - Pentagon plans boost for basic research. PMID- 17729668 TI - Oil in salt domes. PMID- 17729669 TI - Thermidor at OTA. PMID- 17729670 TI - POLYMODE: Exploring the Undersea Weather. PMID- 17729671 TI - A taste of satellite oceanography. PMID- 17729672 TI - Any horse trader could have told you. PMID- 17729673 TI - Instructions for contributors. PMID- 17729674 TI - Annual meeting san francisco. PMID- 17729675 TI - The claims of science. PMID- 17729676 TI - Insects: evolutionary strategies. PMID- 17729678 TI - Stellar rotation. PMID- 17729677 TI - Cases of starvation. PMID- 17729679 TI - Hypolinimetic oxygen deficits: their prediction and interpretation. AB - Rates of hypolimnetic oxygen depletion can be predictedfrom a knowledge of a lake's phosphorus retention, the average hypolimnetic temperature, and the mean thickness of the hypolimnion. Areal oxygen deficits cannot be used to index lake trophic status because areal calculations do not eliminate the influence of hypo limnetic morphometry. PMID- 17729680 TI - Photooxidation of anthracene on atmospheric particulate matter. AB - Anthracene that has been dispersed into atmospheric particulate matter is photooxidized to an array of products reminiscent of oxidation by singlet oxygen in the solution phase. Photooxidation is a more important degradative pathway under ambient conditions than ozonation. Significant disappearance of anthracene also occurs by pathways not involving oxygenation. PMID- 17729681 TI - Atmospheric burnup of the cosmos-954 reactor. AB - On 24 January 1978 the Russian satellite Cosmos-954 reentered the atmosphere over northern Canada. By use of high-altitude balloons, the atmosphere was sampled during 1978 up to an altitude of 39 kilometers to detect particulate debris from the reactor on board the satellite. Enriched uranium-bearing aerosols at concentrations and particle sizes compatible with partial burnup of the Cosmos 954 reactor were detected only in the high polar stratosphere. PMID- 17729682 TI - Remote detection of biological stresses in plants with infrared thermometry. AB - Green leaves of mature sugar beets infected with Pythium aphanidermatum and cotton infected with Phymatotrichum omnivorum had midday radiant leaf temperatures 3 degrees to 5 degrees warmer than adjacent plants with no sign of disease. The temperature difference persisted under varying conditions of soil moisture and could be used to detect biological stress imposed by these soilborne root-rotting fungi. PMID- 17729684 TI - PRODUCTS and MATERIALS. PMID- 17729683 TI - Changed lyotropic liquid crystalline structure due to polymerization of the amphiphilic component. AB - Optical patterns in polarized light and x-ray reflections in the low-angle region were used to detect a shift from one liquid crystalline structure to another during polymerization. The polymerization took place in a Iotropic liquid crystal of water and sodium undecenoate, with a structure consisting of cylinders in a two-dimensional hexagonal close packing. After polymerization, a lamellar liquid crystalline structure was obtained. PMID- 17729685 TI - CABLE STREET-RAILWAYS. PMID- 17729686 TI - THE PHYSICAL BASIS OF AESTHETICS. PMID- 17729687 TI - RECENT PALEONTOLOGICAL PUBLICATIONS. PMID- 17729688 TI - The Millionth Map of Hispanic America. PMID- 17729689 TI - Congratulatory Address. PMID- 17729690 TI - Rate of Enzymic Digestion of Proteins as a Factor in Nutrition. PMID- 17729691 TI - Deposition of Calcium Phosphates Accompanying Senile Degeneration and Disease. PMID- 17729692 TI - A "Frenching" Response of Tobacco Seedlings to Isoleucine. PMID- 17729693 TI - On the Specificity of Epidemic and Murine Typhus. AB - The specificity of epidemic and murine typhus has been shown by active immunization of mice with killed rickettsial suspensions and subsequent challenge with heterologous and homologoustoxic substance. During the preparation of this manuscript, Fitzpatrick published findings showing that 3 of 8 mice immunized with murine typhus vaccine were protected against 3 MLD of epidemic toxic substance administered intravenously and that 8 of 16 mice immunized with epidemic vaccine were protected against < 1 MLD of murine typhus rickettsiae administered intraperitoneally (2). These results suggested to Fitzpatrick that the toxic factor in the two strains is identical. Although there are antigens common to both strains, our findings do not support the suggestion that the two toxic substances are identical. PMID- 17729695 TI - The Target Area of Mammalian Red Cells. PMID- 17729694 TI - Soil Nitrogen and Thrips Injury to Spinach. PMID- 17729696 TI - D. F. J. Lynch 1891-1945. PMID- 17729697 TI - Quantitative Differentiation of Minute Amounts of the Coproporphyrin Isomers (I and III) Based on Fluorescence Behavior. PMID- 17729698 TI - An Instrument for Determining the Partial Pressure of Oxygen in a Gas. PMID- 17729699 TI - The Use of Ultraviolet Light in Tracing the Course of a Drug Through the Body. PMID- 17729700 TI - Modification of Metabolism Apparatus. PMID- 17729701 TI - Malaria and Rainfall Periodicity in Palestine. PMID- 17729702 TI - Museum of Science and Industry. PMID- 17729703 TI - The McDonald Observatory. PMID- 17729704 TI - Virus Encephalomyelitis in Buffaloes. PMID- 17729705 TI - Malaria and Rainfall Periodicity in Palestine. PMID- 17729706 TI - THE ROLE OF SCIENCE INSTITUTIONS IN OUR CIVILIZATION. PMID- 17729707 TI - SMITHSONIAN ENTERPRISES. PMID- 17729709 TI - THE PROFESSIONAL TRAINING OF CHEMISTS. PMID- 17729708 TI - DAVID WILLIAM CORNELIUS. PMID- 17729710 TI - A BRITISH VETERINARY EDUCATIONAL TRUST. PMID- 17729711 TI - FELLOWSHIPS OF THE LALOR FOUNDATION. PMID- 17729712 TI - AMERICAN STANDARDS FOR 1942. PMID- 17729714 TI - THE AMERICAN SOCIETIES OF AGRONOMY AND SOIL SCIENCE. PMID- 17729713 TI - EXPEDITION OF THE DEPARTMENT OF TROPICAL RESEARCH OF THE NEW YORK ZOOLOGICAL SOCIETY. PMID- 17729715 TI - RECENT EVIDENCE REGARDING THE NATURE OF VIRUSES. PMID- 17729716 TI - TRANSPARENT CALCIUM INCRUSTATION OVER ROCK PAINTINGS. PMID- 17729717 TI - ENZYME ACTION. PMID- 17729718 TI - SOME EARLY AMERICAN MUSEUMS. PMID- 17729720 TI - VITAMIN C CONTENT OF PERSIMMON LEAVES AND FRUITS. PMID- 17729719 TI - ANTIBACTERIAL PROPERTIES OF PROTAMINE AND HISTONE. PMID- 17729721 TI - THE EFFECT OF VITAMIN E ON THE BLOOD PLASMA LIPIDS OF THE CHICK. PMID- 17729722 TI - A SEROLOGICALLY ACTIVE POLYSACCHARIDE FROM TRICHINELLA SPIRALIS. PMID- 17729725 TI - SCIENCE NEWS. PMID- 17729724 TI - A SPORULATION STOCK MEDIUM FOR YEASTS AND OTHER FUNGI. PMID- 17729726 TI - THE GOVERNMENT'S RESPONSIBILITIES IN SCIENCE. PMID- 17729729 TI - EDEMA AND GENERAL ATROPHY IN STENOSTOMUM OESOPHAGIUM. PMID- 17729728 TI - BANG'S ABORTION DISEASE OF CATTLE. PMID- 17729727 TI - PEARY'S DISCOVERY OF THE NORTH POLE. PMID- 17729730 TI - A STUDY OF THE RELATION OF THE RELATIVE SIZE OF THE TWO HANDS TO SPEECH. PMID- 17729731 TI - A NEW STAINING METHOD FOR STRUCTURES OF THE SPINAL CORD. PMID- 17729732 TI - APPARATUS FOR DUSTING SULFUR ON PLANTS IN CONTROLLED AMOUNTS. PMID- 17729734 TI - A RAPID METHOD FOR REMOVING COVER GLASSES OF MICROSCOPE SLIDES. PMID- 17729733 TI - X-RAY DIFFRACTIONS FROM HEMOGLOBIN AND OTHER CRYSTALLINE PROTEINS. PMID- 17729735 TI - EFFECTS OF THEELIN ON THE MALE GENITAL TRACT. PMID- 17729736 TI - ON THE TEACHING OF ANATOMY TO ADVANCED MEDICAL STUDENTS. PMID- 17729737 TI - TIME-SERVICE OF HARVARD COLLEGE OBSERVATORY. PMID- 17729738 TI - A SERIES OF ABNORMAL AILANTHUS LEAFLETS. PMID- 17729740 TI - SUGGESTIONS AS TO TEACHING BOTANY IN HIGH SCHOOLS. PMID- 17729739 TI - LATEST DETAILS CONCERNING THE GERMS OF INFLUENZA. PMID- 17729741 TI - A NEURO-EPITHELIOMA OF THE RETINA. PMID- 17729742 TI - A SEEDLING BLACKABERRY PLANT. PMID- 17729743 TI - Hypnotism among the Lower Animals. PMID- 17729744 TI - NOTES ON THE FOOD OF THE BOX TORTOISE. PMID- 17729745 TI - BACTERIOLOGY IN OUR MEDICAL SCHOOLS. PMID- 17729746 TI - CHEMICAL LABORATORY OF THE ALABAMA POLYTECHNIC INSTITUTE. PMID- 17729748 TI - MENTAL SCIENCE. PMID- 17729747 TI - ONE YEAR OF INTERSTATE COMMERCE CONTROL. - WHO IS THE GAINER? PMID- 17729749 TI - Dried Heads among the Jivaros. PMID- 17729750 TI - Landing Eskimo Boats. PMID- 17729751 TI - Vermin-Eaters. PMID- 17729752 TI - Effect of Pressure on Ice. PMID- 17729753 TI - VITAMINS IN OUR FOOD. PMID- 17729754 TI - THOMAS MIDGLEY, JR: An Appreciation. PMID- 17729756 TI - PRESENTATION OF THE NOBEL PRIZES. PMID- 17729755 TI - GRANTS OF THE NATIONAL FOUNDATION FOR INFANTILE PARALYSIS. PMID- 17729757 TI - IN HONOR OF JAMES MURRAY LUCK. PMID- 17729758 TI - THE NEW YORK ACADEMY OF SCIENCES. PMID- 17729759 TI - FELLOWSHIPS IN THE MEDICAL SCIENCES OF THE NATIONAL RESEARCH COUNCIL. PMID- 17729761 TI - HUMAN GENETICS AND ANTHROPOLOGY. PMID- 17729762 TI - PHOTOGRAPHY OF CRYSTAL STRUCTURES. PMID- 17729760 TI - THE MAGNIFICATION OF DIFFERENCES BY A THRESHOLD. PMID- 17729764 TI - THE NAPLES ZOOLOGICAL STATION. PMID- 17729763 TI - DATA ON CANCER THERAPY. PMID- 17729765 TI - THE METABOLISM OF THE KIDNEY. PMID- 17729766 TI - THE MILK AGENT IN SPONTANEOUS MAMMARY CARCINOMA. PMID- 17729767 TI - INHIBITION OF THE BACTERIOSTATIC ACTION OF MALACHITE GREEN BY ITS LEUCOBASES. PMID- 17729768 TI - RELATIVE POTENCY AS APPLIED TO THE ASSAY OF PENICILLIN. PMID- 17729770 TI - BIOLOGICAL STURVEY OF INDIANA. PMID- 17729769 TI - BOTANY AT THE FAIR. PMID- 17729771 TI - PROGRESS IN SANITARY SCIENCE IN MASSACHUSETTS. PMID- 17729773 TI - ALTITUDE AS THE CAUSE OF THE GLACIAL PERIOD. PMID- 17729772 TI - ASEPSIS--PREVENTION BETTER THAN CURE. PMID- 17729774 TI - THE "GOPHER FROG.". PMID- 17729775 TI - NOTES ON THE DISTRIBUTION OF SOME OF THE CONIFERS OF NORTH-WESTERN CANADA. PMID- 17729776 TI - NATURE'S ROTATION OF CROPS. PMID- 17729777 TI - THE SO-CALLED SAND OF GREAT SALT LAKE. PMID- 17729779 TI - PRELIMINARY NOTE ON THE COTTONY SCALE OF THE OSAGE ORANGE. PMID- 17729778 TI - THIE AFFINITIES OF BASQUE AND BERGER. PMID- 17729780 TI - A SPACE-RELATION OF NUMBERS. PMID- 17729781 TI - WORMS ON THE BRAIN OF A BIRD. PMID- 17729782 TI - MINERAL WAX. PMID- 17729783 TI - EXPLOSIVE GAS IN HOT WATER APPARATUS. PMID- 17729784 TI - THEORY OF COLOR SENSATION. PMID- 17729785 TI - A MAYA MONTH-NAME--KHMERS. PMID- 17729786 TI - ANIMAL VOCABULARIES. PMID- 17729787 TI - CURRENT NOTES ON ANTHROPOLOGY.--NO. XXXII. PMID- 17729788 TI - NOTE ON CROTALUS ADAMANTEUS. PMID- 17729789 TI - Federal Executive Salaries. PMID- 17729790 TI - Dislocation Movements in Metals. PMID- 17729791 TI - Scientific Advice for Congress. PMID- 17729792 TI - Scientific Gloom: Congressional Actions Have Stirred Pessimism but Little of It Is Justified. PMID- 17729793 TI - California: As Enrollment Bulge Hits Higher Education System, State Banks on its Master Plan. PMID- 17729794 TI - Decontamination of Potato Tubers Containing Cesium-137. AB - Stirring for 16 hours at 26 degrees to 35 degrees C of peeled and sliced tubers in a solution consisting of 1.2 percent KCI and 0.16 percent NaCl and containing a cation-exchange resin in the mixed K(+), Na(+) form effected Cs(187) removals exceeding 95 percent. Neither nutritional value nor palatability of the tubers was palatable) than normal tubers. PMID- 17729795 TI - Pteropod Ooze from Bermuda Pedestal. AB - Twenty pteropod species and two subspecies are present in the Bermuda Pedestal pelagic sediments. Some species having thin, fragile shells were absent from the sediments but present in the deep water off Bermuda. The subarctic species was present only in the sediments, which indicates that the subarctic current probably invaded the Bermuda region some time ago. PMID- 17729796 TI - Excretion of Hypertonic Urine by a Teleost. AB - During the course of adaptation to sea water, Fundulus kansae excretes urine that is hypertonic to the blood, but hypotonic to sea water. During this period the osmotic pressure of the serum is greater than that found in animals adapted to fresh water or sea water. The urine collected from fish adapted to sea water is usually isotonkc to the blood. route, presumably the gills. PMID- 17729797 TI - Freezing and Viability of Tetrahymena pyriformis in Dimethylsulfoxide. AB - Ciliated protozoa may be preserved at very low temperatures. Tetrahymena pyriformis, suspended in 10 percent dimethylsulfoxide, survived when frozen in two steps, first to -20 degrees C, then transferring immediately to a temperature of -196 degrees C. Motility and ability to reproduce were recovered after freezing by this method and subsequent storage for 3 months in a liquid nitrogen refrigerator. PMID- 17729798 TI - Allotropy in Some Rare-Earth Metals at High Pressures. AB - Allotropes of lanthanum, cerium, praseodymium, and neodymiumc have been observed at elevated pressures with an x-ray diffraction camera which incorporates a diamondanvil, high-pressure cell. In each case a high-pressure modification was observed which has a face-centered cubic structure. At room temperature the unit cell dimensions (alphao) for the high-pressure face-centered cubic structures and approximate pressures at which they were determined are as follows: La, 5.17 A(23 kb); Ce, 4.82 A(15 kb); Pr, 4.88 A(40 kb); and Nd, 4.80 A(50 kb). The unit cell dimensions for the high-pressure forms of La, Pr, and Nd apparently have never been reported. PMID- 17729799 TI - Ferric Tourmaline from Mexico. AB - Dark brown crystals, up to 10 mm long, occur in rhyolite at Mexquitic, San Luis Potosi, Mexico. They are short prismatic, showing {1120}, {3030}, {1011}, {0221}, with c/a 0.4521, measured with a goniometer, and distinct {1120} cleavage. With an unusual combination of cell dimensions, high density, high refractive indices, and extreme birefringence, this tourmaline falls outside the known elbaite-schorl and schorl-dravite series. A chemical analysis, recalculated on the basis of cell volume and density, gives close to the theoretical 150 atoms per cell, whether the iron is ferrous or ferric, but the physical properties indicate a ferric tourmaline. PMID- 17729800 TI - Ferrosilite (FeSiO3): Synthesis at High Pressures and Temperatures. AB - The FeSiO(3) (ferrosilite) end member of the pyroxene series is not known as a pure mineral in nature and cannot be synthesized at atmospheric pressure. It is readily synthesized, however, at pressures from 18 to 45 kb and temperatures from 1150 degrees to 1400 degrees C. Its refractive indices approach those predicted for ferrosilite and it melts incongruently to an Fe, SiO(4)-rich liquid plus quartz. PMID- 17729801 TI - Temperature of Metallic Objects in Space. PMID- 17729802 TI - I. Q., Genetics, and Culture. PMID- 17729803 TI - Initiation of Labor. PMID- 17729804 TI - Arachnid Behavior. PMID- 17729805 TI - Prenatal Irradiation: Effects on the Development of the Central Nervous System and Postnatal Behavior. PMID- 17729806 TI - Forthcoming Events. PMID- 17729807 TI - AIMS OF LABORATORY TRAINING. PMID- 17729808 TI - WEEDS AS FERTILIZING MATERIAL. PMID- 17729810 TI - THE TEXAS ACADEMY OF SCIENCE. PMID- 17729809 TI - NOTES ON LOCAL MEMBRACIDAe AND FULGORIDAe. PMID- 17729812 TI - European Origin of the White Race. PMID- 17729811 TI - Causes which Produce Cold, and Mild Periods. PMID- 17729813 TI - SCIENCE NEWS. PMID- 17729814 TI - A BOTANICAL PROBLEM. PMID- 17729815 TI - HERBERT HOOVER AND SCIENCE. PMID- 17729816 TI - ORIGIN OF PALOUSE HILLS TOPOGRAPHY. PMID- 17729818 TI - WHY PATHOGENE RATHER THAN PATHOGEN? PMID- 17729817 TI - A FOSSIL CYCAD IN NEW JERSEY. PMID- 17729819 TI - PLURAL FRACTIONS. PMID- 17729820 TI - A METHOD OF STAINING THE OOCYSTS OF COCCIDIA. PMID- 17729821 TI - ON A RELEASE-PHENOMENON IN ELECTRICAL STIMULATION OF THE "MOTOR" CEREBRAL CORTEX. PMID- 17729822 TI - THE LIGATION OF EARTHWORMS TO REMOVE THE ANTERIOR OR POSTERIOR END. PMID- 17729823 TI - THE ETIOLOGY OF SWINE INFLUENZA. PMID- 17729825 TI - Irradiated food. PMID- 17729824 TI - MEASURING ABSORBED PHOSPHATES AND NITROGEN. PMID- 17729827 TI - Crystalline anisotropy. PMID- 17729826 TI - Crystalline anisotropy. PMID- 17729828 TI - National security and scientific training. PMID- 17729829 TI - Erratum. AB - In the article "NIMH faces renewed uncertainties" by Jeffrey L. Fox (News and Comment, 13 July, p. 148), the first sentence of the first full paragraph of column 2 on page 149 was incorrectly printed. The sentence should have begun, "The 1985 budget for research calls for a modest increase...." PMID- 17729830 TI - Soluble lectins. PMID- 17729831 TI - Soluble lectins. PMID- 17729832 TI - Xochicalco: urban growth and state formation in central Mexico. AB - The appearance of regional city-states in pre-Hispanic Central Mexico corresponds with the disruption of socioeconomic relationships throughout Teotihuacan's political domain after 650 A.D. Surface reconnaissance and mapping at Xochicalco provided information on the growth and organization of one of these urban centers. The data indicate that Xochicalco was a well-planned urban center and capital of a regional city-state that extended its domain throughout western Morelos by military conquest. PMID- 17729833 TI - Technological trends in automobiles. AB - Current technological trends in the automotive industry reflect many diverse disciplines. Electronics and microprocessors, new engine transmission concepts, composite and ceramic materials, and computer-aided design and manufacture will combine to make possible the creation of advanced automobiles offering outstanding quality, fuel economy, and performance. A projected "average" vehicle of the 1990's is described to illustrate the application of these new concepts. PMID- 17729834 TI - Star Wars Chief Takes Aim at Critics: He says the program is feasible and expects deployment by the year 2000; convincing Congress and scientific skeptics will not be easy. PMID- 17729835 TI - A dim future for weapons talks. PMID- 17729837 TI - Comings and goings. PMID- 17729836 TI - House prepares to slash synthetic fuels agency. PMID- 17729838 TI - U.s.-Poland exchanges remain uncertain. PMID- 17729839 TI - EPA to repair leaks in leaded gasoline rules. PMID- 17729840 TI - Artificial Intelligence in Parallel: Working with many processors at once could accelerate computation enormously--and suggest new ways to think about thinking. PMID- 17729842 TI - Morphology of cortical cells: cerebral cortex. PMID- 17729841 TI - Parks: How Big Is Big Enough?: A major ecological experiment in the Amazon rain forest addresses the crucial size question of national parks. PMID- 17729843 TI - Stellar atmospheres: the a-stars. PMID- 17729845 TI - Actinopterygian neurobiology: fish neurobiology. PMID- 17729844 TI - Marine zoogeography: a comparative atlas of zooplankton. PMID- 17729846 TI - Some other books of interest: explorations in the history of psychology in the United States. PMID- 17729848 TI - Some other books of interest: science in government. PMID- 17729847 TI - Some other books of interest: uncommon sense. PMID- 17729849 TI - Multiple thermal maxima during the holocene. AB - The astronomical theory of climatic change provides an alternative to the traditional chronology for Holocene climatic change, which calls for one thermal maximum about 6000 years ago. The theory predicts a series of maxima during the Holocene, one for each season. Because the relation of the perihelion to the spring equinox changes with a 22,000-year period, late summer insolation would have been greatest 5000 years ago, whereas early summer insolation would have been greatest 13,000 years ago. Climatic reconstructions based on the response of ecosystems to late summer climate indicate a later Holocene thermal maximum than paleoclimatic data sensitive to early summer climate. In southern Idaho, three different vegetation types indicate thermal maxima at different times during the Holocene, depending on the climatic variable controlling each type. PMID- 17729850 TI - The fine structure of fossil plant cell walls. AB - The cell walls of sieve elements in the primary phloem of the Carboniferous fern Tubicaulis contain structural features that morphologically resemble cellulose microfibrils in extant plants. This may be the oldest example of distinct fibrillar structures in the fossil record. The possible identity and significance of these features are discussed and their structure is compared with that of cell walls in other fossil and extant plants. PMID- 17729851 TI - New radiocarbon dates on the cereals from wadi kubbaniya. PMID- 17729853 TI - Erratum. AB - In the report "Access of urinary nonvolatiles to the mammalian vomeronasal organ" by C. J. Wysocki et al. (15 Feb., p. 781), the parts of Fig. I were inadvertently interchanged. PMID- 17729852 TI - University-industry programs. AB - In the report by R. G. Wyatt et al. "Human rotavirus type 2: Cultivation in vitro" (11 Jan., p. 189), in the sentence describing the porcine rotavirus plaque reduction test (p. 190, column 3, line 16), the concentration of pancreatin in the agar overlay should have been given as "0.15 percent of 2.5 percen pantreatin 4 x N. F.; Gibco." PMID- 17729854 TI - Federal support in the social sciences. PMID- 17729855 TI - The potential for grass-fed livestock: resource constraints. AB - Using pasture and grazed forest-range for a system of producing live-stock by feeding grass alone reduces the inputs of energy about 60 percent and land resources about 8 percent, but also reduces by about half the production of animal protein in the United States. Under a system in which only grass was fed, livestock would be restricted to beef, milk, and lamb production. The amount of grain fed to U.S. livestock is about 135 million tons (metric) or about ten times the amount consumed by the U.S. population. PMID- 17729856 TI - Assault on research secrets at pentagon. PMID- 17729857 TI - Carter creates state radwaste council. PMID- 17729858 TI - Army to lose overseas labs. PMID- 17729859 TI - Deutch to Leave DOE. PMID- 17729860 TI - Bursts of gamma rays baffle astronomers. PMID- 17729861 TI - 1979 report of the executive officer. PMID- 17729862 TI - Sexuality: attempts at a broad view. PMID- 17729863 TI - Experimental model. PMID- 17729864 TI - French science policy. PMID- 17729866 TI - Astronomical phenomena. PMID- 17729865 TI - Crystalline solids. PMID- 17729867 TI - Radon Anomaly: A Possible Precursor of the 1978 Izu-Oshima-kinkai Earthquake. AB - Precursory changes in the radon concentration of groundwater were observed prior to the Izu-Oshima-kinkai earthquake (magnitude 7.0) 14 January 1978. The distance from the epicenter to a continuous radon-monitoring station at Nakaizu was about 25 kilometers. A sudden drop and a subsequent increase in the radon concentration recorded on 9 January 1978 were significant. The size of the spike-like change was about 15 percent. After the earthquake, a remarkable increase in the radon concentration occurred. PMID- 17729868 TI - Heat Transport by Currents Across 25{degrees}N Latitude in the Atlantic Ocean. AB - The heat transported by currents across 25 degrees N in the Atlantic Ocean is estimated from oceanographic measurements to be 1.1 x 10(15) watts northward. This figure agrees, within estimated error, with the value obtained from charts of energy exchange between ocean and atmosphere but is smaller by a factor of 2 than the recent value derived from satellite radiation measurements. PMID- 17729869 TI - Free-radical oxidants in natural waters. AB - Photooxidation of cumene (isopropylbenzene) and pyridine in dilute solution in natural waters gives products characteristic of reactions with alkylperoxy (RO(2).) and hydroxyl (HO.) radicals. On the basis of the rates of formation of the products, the average concentrations of RO(2). and HO. are estimated to be about 10(-9) and 10(-17) mole per liter, respectively. The concentration of RO(2). is large enough that, for some classes of reactive chemicals, oxidation can be an important process in natural waters. PMID- 17729870 TI - 2-Tridecanone: A Naturally Occurring Insecticide from the Wild Tomato Lycopersicon hirsutum f.glabratum. AB - A nonalkaloid insecticide was isolated from the wild tomato Lycopersicon hirsutum f. glabratum and identified as 2-tridecanone, a compound 72 times more abundant in the wild tomato than in the cultivated tomato L. esculentum. Lepidopterous larvae (Manduca sexta and Heliothis zea) and aphids (Aphis gossypii) died when confined on 2-tridecanone-treated filter paper. PMID- 17729871 TI - Cryptic self-fertilization in the malpighiaceae. AB - Some Malpighiaceae produce minute cleistogamous flowers in addition to showy chasmogamous flowers. Standard techniques fail to reveal how the cleistogamous flowers achieve self-fertilization. Fluorescence in longitudinal sections shows that the pollen germinates inside the indehiscent anther. The pollen tubes then grow down through the filament,. into the receptacle, up into the carpels, and into the nucellar beak of the ovule. PMID- 17729872 TI - Feedback control of juvenile hormone synthesis in cockroaches: possible role for ecdysterone. AB - Inactive female corpora allata implanted into adult males become active and continue to synthesize juvenile hormone at high rates. However, when an ovary is implanted together with the corpora allata, rates of juvenile hormone synthesis decline as the oocytes complete maturation. Injections of ecdysterone mimic the effect of an implanted ovary. PMID- 17729874 TI - PRODUCTS and MATERIALS. PMID- 17729873 TI - Multiple daily amphetamine administration: behavioral and neurochemical alterations. AB - In rats, multiple daily amphetamine injections (2.5 milligrams per kilogram of body weight, injected subcutaneously every 4 hours for 5 days) resulted in a progressive augmentation in response, characterized by a more rapid onset and an increased magnitude of stereotypy. By contrast, offset times of both the stereotypy and the poststereotypy hyperactivity periods were markedly shortened. When the animals were retested with the same dose of amphetamine 8 days after the long-term treatment was discontinued, the time of offset of the stereotypy and hyperactivity phases had recovered to values found with short-term amphetamine treatment, whereas the more rapid onset of stereotypy persisted. Brain monoamine and amphetamine concentrations and tyrosine hydroxylase activity were determined in comparably treated rats at times corresponding to the behavioral observations. The behavioral data indicate that enhanced responsiveness to amphetamine following its repeated administration may contribute to the development of amphetamine psychosis. PMID- 17729875 TI - Cancer and mental illness. PMID- 17729876 TI - Tanker safety: vessel traffic control? PMID- 17729877 TI - The management of weather resources. PMID- 17729878 TI - A terminal mesozoic "greenhouse": lessons from the past. AB - The late Mesozoic rock and life records implicate short-term (up to 10(5) to 10(6) years) global warming resulting from carbon dioxide-induced "greenhouse" conditions in the late Maestrichtian extinctions that terminated the Mesozoic Era. Oxygen isotope data from marine microfossils suggest late Mesozoic climatic cooling into middle Maestrichtian, and warming thereafter into the Cenozoic. Animals adapting to climatic cooling could not adapt to sudden warming. Small calcareous marine organisms would have suffered solution effects of carbon dioxide-enriched waters; animals dependent upon them for food would also have been affected. The widespread terrestrial tropical floras would likely not have reflected effects of a slight climatic warming. In late Mesozoic, the deep oceanic waters may have been triggered into releasing vast amounts of carbon dioxide into the atmosphere in a chain reaction of climatic warming and carbon dioxide expulsion. These conditions may be duplicated by human combustion of the fossil fuels and by forest clearing. PMID- 17729879 TI - American-soviet relations: the canceled computer. PMID- 17729880 TI - Scientists want soviet contacts kept. PMID- 17729881 TI - Detour on the road to brave new world. PMID- 17729882 TI - Post-apollo astronauts train for shuttle. PMID- 17729883 TI - NRC Study Tracks Trends in Doctorates. PMID- 17729884 TI - Endangered species act survives senate hunters. PMID- 17729885 TI - Erratum. AB - In the 30 June issue of Science, p. 1466 Mark Ptashne was incorrectly identified as a member of the faculty of Harvard Medical School. Ptashne is professor of biochemistry and molecular biology at Harvard University. PMID- 17729886 TI - Ultrahigh pressure: new highs spur pursuit of exotic goals. PMID- 17729888 TI - Math called key to Indian self-determination. PMID- 17729887 TI - Holographic filing: an industry on the verge of birth. PMID- 17729889 TI - For the library. PMID- 17729890 TI - Change in section h election slate. PMID- 17729891 TI - Science education for handicapped theme of conference. PMID- 17729892 TI - 1977 aaas summary financial statements. PMID- 17729893 TI - Annual meeting houston. PMID- 17729895 TI - Atmospheric phenomena. PMID- 17729894 TI - The kuhnian perspective. PMID- 17729896 TI - Evolutionary mechanisms. PMID- 17729897 TI - Velocity anomalies in dilatant rock. AB - Seismic velocities measured in rock deformed in the laboratory show excellent agreement with theoretical predictions of the effects of crack growth during dilatancy. Under appropriate conditions dilatancy was observed to produce a drop in the ratio of the seismic compressional velocity to the seismic shear velocity both by the mechanism of undersaturation and by a liquid-gas phase transition. PMID- 17729898 TI - Flowering Induced on Young Loblolly Pine Grafts by Out-of-Phase Dormancy. AB - Loblolly pine trees 3 to 7 years old grown in a heated greenhouse under a 20-hour photoperiod had quiescent buds induced by lowering the temperature and shortening the photoperiod. This treatment resulted in the formation of both male and female strobili. Overall, 38 percent of the ramets produced females, and 68 percent produced males. There was no significant difference in the frequency of flowering among 3-, 5-, and 7-year-old scions. PMID- 17729899 TI - Mutant Strains of Rhizobium japonicum with Increased Ability to Fix Nitrogen for Soybean. AB - A strain of Rhizobium japonicum used in commercial inoculants was mutagenized and screened by a rapid effectiveness assay with soybean plants. Two mutant strains nodulated the roots earlier than the wild type and also expressed greater symbiotic nitrogen-fixing activity than the wild type in the presence and absence of fixed nitrogen. In addition, one of the mutants formed more root nodules than the wild type. Plants inoculated with these strains had increased dry weights ( approximately 60 percent) and nitrogen content ( approximately 100 percent) when grown in growth chambers. PMID- 17729900 TI - Proteins in a nonvenomous defensive secretion: biosynthetic significance. AB - In common with many arthropods, the true bug, Leptoglossus phyllopus, when disturbed, emits a two-phase secretion that consists of an organic phase and an aqueous phase. The organic phase is a mixture of highly reactive low-molecular weight compounds, analogous to those produced by other arthropods, and is deterrent to many kinds of predators. The aqueous phase, heretofore ignored in most analyses of arthropod defensive secretions, contains proteins. Even though the secretion is not injected, the proteins enzymatically catalyze the derivation of the most reactive components within the impermeable cuticular storage reservoir and, thus, constitute part of the defensive system that appears to be commonly used by arthropods producing irritating chemicals. PMID- 17729902 TI - COMMENT AND CRITICISM. PMID- 17729901 TI - Biosynthesis and Accumulation of Formic Acid in the Poison Gland of the Carpenter Ant Camponotus pennsylvanicus. AB - Formic acid synthesis in the poison gland of Camponotus pennsylvanicus is closely related to the C-1 metabolism of the glandular cells. Serine, glycine, and histidine are potential C-l donors to formic acid by several tetrahydrofolate intermediates. Formic acid is accumulated by its transfer to an insulated reservoir, so that the ant avoids the acid's cytotoxicity. This combination of biochemical and morphological features provides an autodefensive mechanism. Possible factors that regulate the biosynthesis of formic acid in the poison gland apparatus are discussed. PMID- 17729903 TI - Capitalization of names of formations. PMID- 17729904 TI - Electric time-signals. PMID- 17729905 TI - Osteology of the cormorant. PMID- 17729906 TI - Chemical geology. PMID- 17729907 TI - Synchronism of geological formations. PMID- 17729908 TI - Remsen's 'Theoretical chemistry.'. PMID- 17729909 TI - A possible solution of the standard time question. PMID- 17729910 TI - Free cervical ribs in the human subject. PMID- 17729912 TI - THE INTELLIGENCE OF BATRACHIANS. PMID- 17729911 TI - WHIRLWINDS, CYCLONES, AND TORNADOES.--VIII. PMID- 17729913 TI - THE PONS-BROOKS COMET. PMID- 17729914 TI - THE AINOS OF YEZO. PMID- 17729915 TI - THE HOT BLAST IN MAKING IRON. PMID- 17729916 TI - MODERN PHYSIOLOGICAL LABORATORIES: WHAT THEY ARE AND WHY THEY ARE.--I. PMID- 17729917 TI - BERTHELOT'S EXPLOSIVE MATERIALS. PMID- 17729919 TI - HOUSTON'S ELEMENTS OF CHEMISTRY. PMID- 17729918 TI - BESANT'S HYDROMECHANICS. PMID- 17729920 TI - INTELLIGENCE FROM AMERICAN SCIENTIFIC STATIONS. PMID- 17729922 TI - A KINETIC THEORY OF EVOLUTION. PMID- 17729921 TI - THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17729923 TI - THE LATE MILES ROCK. PMID- 17729924 TI - OTTO LUGGER. PMID- 17729925 TI - REMARKABLE DISCOVERIES. PMID- 17729926 TI - WHAT IS LIFE? PMID- 17729928 TI - AN EARTHWORK DISCOVERED IN MICHIGAN. PMID- 17729927 TI - PHYSIOLOGY IN THE SCHOOLS. PMID- 17729929 TI - A 'SAND-BOW'--AN UNUSUAL OPTICAL PHENOMENON. PMID- 17729930 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17729931 TI - NOTES ON INORGANIC CHEMISTRY. PMID- 17729932 TI - SCIENTIFIC POSITIONS UNDER THE GOVERNMENT. PMID- 17729933 TI - THE AMERICAN ASSOCIATION. PMID- 17729934 TI - CONVOCATION WEEK. PMID- 17729935 TI - THE NEXT FIFTY YEARS. PMID- 17729936 TI - HYPOTHESIS AS TO THE ORIGIN OF COSMIC RAYS AND THE EXPERIMENTAL TESTING OF IT IN INDIA AND ELSEWHERE. PMID- 17729937 TI - THE DEPARTMENT OF ASTRONOMY OF THE UNIVERSITY OF CHICAGO. PMID- 17729939 TI - THE WARTIME SERVICE OF BIOLOGICAL ABSTRACTS. PMID- 17729938 TI - WALTER GRANGER. PMID- 17729940 TI - NEW TYPHUS VACCINE BEING TESTED IN BOLIVIA. PMID- 17729941 TI - THE MATHEMATICIANS OF AMERICA AND OF SOVIET RUSSIA. PMID- 17729942 TI - RETIREMENTS AT THE OHIO STATE UNIVERSITY. PMID- 17729943 TI - CENSUS OF SCIENTIFIC AND SPECIALIZED WORKERS IN THE UNITED STATES AND IN OTHER COUNTRIES. PMID- 17729944 TI - THE VERTICAL DISTRIBUTION OF HEAVY MINERALS IN VIRGIN AND CULTIVATED SOILS. PMID- 17729945 TI - THE FIRST MATHEMATICS SECTION OF THE NATIONAL ACADEMY OF SCIENCES. PMID- 17729947 TI - REPORTING DATA ON ELECTRIC MOBILITY. PMID- 17729946 TI - ANTIDOTING TOXIN OF PHYTOPHTHORA CACTORUM AS A MEANS OF PLANT DISEASE CONTROL. PMID- 17729948 TI - THE EFFECT OF 17-HYDROXYCORTICOSTERONE AND RELATED ADRENAL CORTICAL STEROIDS ON SODIUM AND CHLORIDE EXCRETION. PMID- 17729949 TI - THE ENZYMATIC LINK BETWEEN DIHYDRO-DIPHOSPHOPYRIDINE NUCLEOTIDE AND CYTOCHROME C. PMID- 17729950 TI - FACTORS IN COCONUT MILK ESSENTIAL FOR GROWTH AND DEVELOPMENT OF VERY YOUNG DATURA EMBRYOS. PMID- 17729951 TI - A MINCER ADAPTABLE TO SMALL QUANTITIES OF TISSUE. PMID- 17729952 TI - A COMBINED FIXATIVE AND STAIN FOR THE CILIA AND TRICHOCYSTS OF PARAMECIUM. PMID- 17729953 TI - Genes as Determiners of Cellular Biochemistry. PMID- 17729954 TI - The Designation of Special Isotopes in the Names and Formulas of Inorganic Compounds. PMID- 17729955 TI - The Common Cold: Titration of MR-1 Virus in Embryonated Eggs. PMID- 17729956 TI - Electron Microfossils. PMID- 17729957 TI - The Aerobee Sounding Rocket--A New Vehicle for Research in the Upper Atmosphere. PMID- 17729958 TI - Metabolism of C14-1abeled Urea. PMID- 17729959 TI - A Plastic Plate for Use in Tests Involving Virus Hemagglutination and Other Similar Reactions. PMID- 17729960 TI - SCIENCE NEWS. PMID- 17729961 TI - WHAT CONSTITUTES PUBLICATION? PMID- 17729962 TI - THE SEVENTH CRUISE OF THE NONMAGNETIC YACHT "CARNEGIE". PMID- 17729964 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17729963 TI - HARRIS HAWTHORNE WILDER. PMID- 17729965 TI - DOES THE AMOUNT OF FOOD CONSUMED INFLUENCE THE GROWTH OF AN ANIMAL? PMID- 17729967 TI - MODELING CLAY AS A SUBSTITUTE FOR COLOPHONIUM WAX IN THE PHYSIOLOGICAL LABORATORY. PMID- 17729966 TI - THE SIBERIAN METEORITE. PMID- 17729968 TI - CONCERNING A RHIZOCTONIA WHICH FORMS HYMENIAL CELLS AND BASIDIOSPORES IN CULTURE. PMID- 17729969 TI - A "DATA" OF RESEARCH. PMID- 17729970 TI - THE USE OF NAPHTHALENE IN NARCOTIZING EARTHWORMS. PMID- 17729971 TI - THE EFFECTS OF SELECTIVE SOLAR RADIATIONS ON GROWTH AND DEVELOPMENT. PMID- 17729972 TI - VITAMIN B--A QUESTION OF NOMENCLATURE. PMID- 17729973 TI - THE FEDERATION OF AMERICAN SOCIETIES OF EXPERIMENTAL BIOLOGY. PMID- 17729974 TI - COMMENT AND CRITICISM. PMID- 17729975 TI - THE EXPLORATION OF THE WELLE. PMID- 17729976 TI - GEOGRAPHICAL NOTES. PMID- 17729977 TI - THE HEALTH OF NEW YORK DURING JANUARY. PMID- 17729978 TI - Inertia-force. PMID- 17729980 TI - On the serpentine of Syracuse, N.Y. PMID- 17729979 TI - The failure of foreign trees on American soil. PMID- 17729981 TI - On the flight of birds. PMID- 17729982 TI - Comparative taxation. PMID- 17729983 TI - Thought-transferrence. PMID- 17729984 TI - Increase of the electrical potential of the atmosphere with elevation. PMID- 17729985 TI - On tiptoe. PMID- 17729986 TI - Science in Less-Developed Countries. PMID- 17729987 TI - The Physician and the Drug Disputes. PMID- 17729988 TI - Prescient. PMID- 17729989 TI - On Quoting. PMID- 17729990 TI - Training in Microbiology. PMID- 17729991 TI - Crackpot Scale Applied. PMID- 17729992 TI - Conventional versus Nuclear Power. PMID- 17729993 TI - The Pleistocene Epoch in Deep-Sea Sediments: A complete time scale dates the beginning of the first ice age at about 1frac12 million years ago. PMID- 17729995 TI - Lunar Notation on Upper Paleolithic Remains: Markings on bones and rock walls dating from the Upper Paleolithic period show accurate lunar observation. PMID- 17729994 TI - Infrared Surveys of Hawaiian Volcanoes: Aerial surveys with infrared imaging radiometer depict volcanic thermal patterns and structural features. AB - Aerial infrared-sensor surveys of Kilauea volcano have depicted the areal extent and the relative intensity of abnormal thermal features in the caldera area of the volcano and along its associated rift zones. Many of these anomalies show correlation with visible steaming and reflect convective transfer of heat to the surface from subterranean sources. Structural details of the volcano, some not evident from surface observation, are also delineated by their thermal abnormalities. Several changes were observed in the patterns of infrared emission during the period of study; two such changes show correlation in location with subsequent eruptions, but the cause-and-effect relationship is uncertain. Thermal anomalies were also observed on the southwest flank of Mauna Loa; images of other volcanoes on the island of Hawaii, and of Haleakala on the island of Maui, revealed no thermal abnormalities. Approximately 25 large springs issuing into the ocean around the periphery of Hawaii have been detected. Infrared emission varies widely with surface texture and composition, suggesting that similar observations may have value for estimating surface conditions on the moon or planets. PMID- 17729996 TI - The Compleat Botanist: Trained botanists with a broad background and a liberal education are urgently needed by society. PMID- 17729998 TI - The Midwest: New Arrangement for Argonne Holds Promise of Greater Federal Financial Aid for Region. PMID- 17729997 TI - Nobel Prize in Chemistry Awarded to Crystallographer. PMID- 17730000 TI - Large New Telescopes for the Southern Hemisphere. PMID- 17729999 TI - Comsat II: Commercial System to Avoid Tie with Defense Department; Company Now Faces Other Problems. PMID- 17730002 TI - Component Shapes in Double Radio Sources. AB - High-resolution interferometry at a wavelength of 10.6 centimeters shows that several well-separated double radio sources have small, bright regions near the outward ends of their components. This is consistent with an expanding model for the sources. PMID- 17730003 TI - Spalled, Aerodynamically Modified Moldavite from Slavice, Moravia, Czechoslovakia. AB - A Czechoslovakian tektite or moldavite shows clear, indirect evidence of aerodynamic ablation. This large tektite has the shape of a teartdrop, with a strongly convex, deeply corroded, but clearly identifiable front and a planoconvex,- relatively . smooth, posterior surface. In spite of much erosion and corrosion, demarcation of the posterior and the anterior part of the specimen (the keel) is clearly preserved locally. This specimen provides the first tangible evidence that moldavites entered the atmosphere cold, probably at a velocity exceeding 5 kilometers per second; the restult was selective heating of the anterior face and perhaps ablation during the second melting. This provides evidence of the extraterrestial origin of moldavites. PMID- 17730001 TI - Air Concentrations of Twelve Radionuclides from 1962 through Mid-1964. AB - New spectrometric techniques for the multidimensional counting of gamma rays permit the direct measurement of twelve radionuclides collected on air filters. Observed concentrations of Be(7), Na(22), Mn(54), Co(60), Y(88), Zr(95)-Nb(25), Ru(166), Sb(124), Sb(125), Cs(134), Cs(137), and Ce(144) during the past 2(1/2) years help to explain the origin and fallout rates of the trace radionuclides in air. PMID- 17730004 TI - Stereopsis Suppression: Addendum. PMID- 17730005 TI - The Social Nature of Man. PMID- 17730006 TI - The Evolution of Galaxies. PMID- 17730007 TI - High-Energy Physics. PMID- 17730008 TI - CONTRIBUTIONS OF MEDICAL RESEARCH IN CHEMICAL WARFARE TO MEDICINE. PMID- 17730009 TI - ROBERT H. GODDARD. PMID- 17730012 TI - THE MAGNUSON BILL. PMID- 17730011 TI - FEDERAL SUPPORT OF SCIENTIFIC RESEARCH. PMID- 17730010 TI - THE SUMMER MEETING OF THE AMERICAN MATHEMATICAL SOCIETY. PMID- 17730014 TI - NEWS FROM ABROAD. PMID- 17730013 TI - RESEARCH INSTITUTIONS OF BIOLOGY. PMID- 17730015 TI - FELLOWSHIPS IN THE MEDICAL SCIENCES OF THE NATIONAL RESEARCH COUNCIL. PMID- 17730016 TI - THE VITAMIN CONTENT OF CASEIN. PMID- 17730017 TI - THE RELATION OF ENDOCRINE GLANDS TO THE GASTRIC SECRETORY DEPRESSANT IN URINE (UROGASTRONE). PMID- 17730018 TI - PRECIPITATION OF FERRIC HYDRATE BY IRON BACTERIA. PMID- 17730019 TI - SHORT AND LONG FOOD CHAINS AMONG VEGETABLE CROPS. PMID- 17730020 TI - THE DESTRUCTION OF PYROGENS BY HYDROGEN PEROXIDE. PMID- 17730021 TI - STIRRER BEARING FROM BROKEN HYPODERMIC. PMID- 17730022 TI - THE WAR AND SCIENCE IN THE PHILIPPINES. PMID- 17730024 TI - PROPOSALS FOR A NATIONAL RESEARCH FOUNDATION. PMID- 17730023 TI - THE AIR FORCES' COLLECTION OF AERIAL PHOTOGRAPHS. PMID- 17730026 TI - SCIENCE NEWS. PMID- 17730025 TI - THE TOXICITY OF DDT TO DAPHNIA. PMID- 17730027 TI - THE AIMS OF ANTHROPOLOGICAL RESEARCH. PMID- 17730028 TI - CONQUEST OF THE PHYSICAL WORLD. PMID- 17730029 TI - OBITUARY. PMID- 17730030 TI - VIABILITY OF DROSOPHILA SPERMATOZOA IN SEA WATER. PMID- 17730031 TI - DISSEMINATION OF SCIENTIFIC KNOWLEDGE. PMID- 17730033 TI - CONSTANT TEMPERATURE APPARATUS ADAPTED FOR USE ON THE MICROSCOPE STAGE. PMID- 17730032 TI - RIVER DEFLECTION: A CORRECTION. PMID- 17730034 TI - PEAT MATS FOR GERMINATION TESTS OF FOREST TREE SEEDS. PMID- 17730035 TI - APPARENT PARTHENOGENESIS IN NATURE, IN A FORM OF FISH OF HYBRID ORIGIN. PMID- 17730036 TI - THE VITAMIN C ACTIVITY OF HEXURONIC ACID FROM SUPRARENAL GLANDS. PMID- 17730038 TI - Habitat. PMID- 17730037 TI - On the dangers of genetic meddling. PMID- 17730039 TI - Housing requirements and national resources. PMID- 17730040 TI - Whither site and services? PMID- 17730041 TI - The rush to the cities in latin america. PMID- 17730042 TI - A stable urban ecosystem. PMID- 17730043 TI - Energy use in rural India. AB - An old saying has it, "slavery will persist until the loom weaves itself." All ancient civilizations, no matter how enlightened or creative, rested on slavery and on grinding human labor, because human and animal muscle power were the principal forms of energy available for mechanical work. The discovery of ways to use less expensive sources of energy than human muscles made it possible for men to be free. The men and women of rural India are tied to poverty and misery because they use too little energy and use it inefficiently, and nearly all they use is secured by their own physical efforts. A transformation of rural Indian society could be brought about by increasing the quantity and improving the technology of energy use. PMID- 17730045 TI - Nuclear Safety: A Federal Adviser's Warnings Provoke Ire of Colleagues. PMID- 17730044 TI - Nuclear initiative: impending vote stimulates legislative action. PMID- 17730046 TI - Sea law treaty: amid u.s. Gains, the prospects for science are sinking. PMID- 17730048 TI - GSI: Heavy-Ion Research as the Future of Nuclear Science. PMID- 17730049 TI - Mathematical proofs: the genesis of reasonable doubt. PMID- 17730047 TI - Dade county: the politics of managing urban growth. AB - This is one of several articles specially prepared for this issue of Science in recognition of Habitat: The United Nations Conference on Human Settlements now taking place in Vancouver. PMID- 17730051 TI - New publications. PMID- 17730050 TI - AAAS Initiates Barrier-Free Meetings. PMID- 17730052 TI - AAAS Receives $75,000 Bequest. PMID- 17730053 TI - Colloquium on R & d in the federal budget. PMID- 17730055 TI - The search for petroleum. PMID- 17730054 TI - SB & F Needs Reviewers. PMID- 17730056 TI - Medical matters in antiquity. PMID- 17730057 TI - Organelle genetics. PMID- 17730058 TI - The integument in arthropoda. PMID- 17730059 TI - Plant physiology. PMID- 17730060 TI - Control of methane sediment-water bubble transport by macroinfaunal irrigation in cape lookout bight, north Carolina. AB - Methane transport by bubble ebullition through bubble tubes from sediments to overlying waters in Cape Lookout Bight, Outer Banks of North Carolina, occurs only in the absence of burrowing macroinfauna, which indirectly prevent saturation methane concentrations by irrigating surface sediments with dissolved sulfate. Distribution of macroinfauna in the bight is limited to bottom areas not subjected to periodic anoxic conditions. PMID- 17730062 TI - Notes from other offices. PMID- 17730061 TI - Meteoroid storms detected on the moon. AB - Seismometers on the moon have detected several brief periods of enhanc ed meteoroid-impact activity, believed to represent encounters of the moon with "c louds" of objec ts in the kilogram range. The latest and most active encounter, in June 1975, is interpreted as a meteoroid c(loud of diameter 0.1 astronomical unit and total mass 10(l3) to 10(14) grams. PMID- 17730063 TI - Recreation: a conservation problem. PMID- 17730064 TI - Letters to the editor. PMID- 17730065 TI - Luna IX Pictures: A Question of Ethics. PMID- 17730066 TI - Letters to the editor. PMID- 17730067 TI - Priority and recognition. PMID- 17730068 TI - Sophistication. PMID- 17730069 TI - Channeling of funds. PMID- 17730070 TI - Letters to the editor. PMID- 17730071 TI - Letters to the editor. PMID- 17730072 TI - Letters to the editor. PMID- 17730073 TI - More about Car Safety. PMID- 17730074 TI - Letters to the editor. PMID- 17730077 TI - Support of science in underdeveloped countries. PMID- 17730076 TI - Woodlands in the great plains. PMID- 17730075 TI - Project orion. PMID- 17730078 TI - Stellar chromospheres. PMID- 17730079 TI - Very fast reactions in solution. PMID- 17730080 TI - M.I.T.: new president will pursue broadened goals. PMID- 17730081 TI - Animal care: the humane movement is pulling ahead. PMID- 17730082 TI - Iron meteorites with low cosmic ray exposure ages. AB - Analysis of argon-38 and argon-39 produced by cosmic rays in four iron meteorites gives normal amounts of the radioactive product argon-39 and abnormally low amounts of stable argon-38. This indicates that these meteorites were exposed to cosmic rays for unusually short periods of time. These exposure times are one or two orders of magnitude shorter than those for the average iron meteorite, and they overlap the periods found for chondrites. It is suggested that perhaps 20 percent of the iron meteorites have similarly short exposure periods. PMID- 17730083 TI - Layer of Abnormally Cold Bottom Water over Southern Aves Ridge. AB - A thermograd record obtained over the Ayes Ridge indicated existence, at the time of observation, of a cold layer of water in the lowest 13 meters, undergoing high frequency internal oscillations. The great discontinuity in temperature across the sedimnent-water interface and the lack of agreement with the normal temperature structure indicate that the layer was a transient feature. This abnormal condition may be related to the passage of a hurricane 3 days earlier. PMID- 17730084 TI - Dislocations in a campo del cielo meteorite. AB - Thin-film transmission electron microscopy showed that a Campo del Cielo meteorite has an immobile dislocation network of high density. The network is not related to attendant precipitates. PMID- 17730085 TI - Chromosome Changes Induced by Infections in Tissues of Rhynchosciara angelae. AB - The main effects of two infections, one by a protozoan and the other by a virus, in cells of Rhynchosciara angelae (Diptera, Sciaridae) are an increase in cell size and changes in the size, shape, and behavior of the chromosomes. The X chromosome of some cells reacts differently from the autosome to the protozoan infection. Some chromosomes show specific, easily traceable points after infection by the virus. Some of the effects of these infections may be similar to the effects of infective agents in other organisms. PMID- 17730086 TI - Russian Luna IX Pictures: Provisional Analysis. PMID- 17730087 TI - Water-drop-producing equipment. PMID- 17730088 TI - Nitrogen fixation. PMID- 17730089 TI - Forthcoming events. PMID- 17730090 TI - THE PHILOSOPHY OF GEOLOGY AND THE ORDER OF THE STATE. PMID- 17730092 TI - REPORT OF THE SUBCOMMITTEE ON RESEARCH FUNDS. PMID- 17730091 TI - REPORT OF THE SUBCOMMITTEE ON ASTRONOMY. PMID- 17730093 TI - REPORT OF THE SUBCOMMITTEE ON CHEMISTRY. PMID- 17730094 TI - THE FUR SEAL CENSUS OF 1916. PMID- 17730095 TI - PROFESSOR CURTIS'S REVIEW OF PETRUNKEVITCH'S MORPHOLOGY OF INVERTEBRATE TYPES. PMID- 17730096 TI - THE OVERLAPPING OF THE LEAF SHEATH AND ITS LACK OF VALUE FOR DESCRIPTIVE BOTANICAL LITERATURE. PMID- 17730097 TI - REPORT OF THE TREASURER FOR 1916. PMID- 17730098 TI - THE AMERICAN ASTRONOMICAL SOCIETY. PMID- 17730099 TI - NEW YORK ACADEMY OF SCIENCES. PMID- 17730101 TI - AN EXPERIMENT UPON ELECTRIC FISH MADE BY GALVANI. PMID- 17730100 TI - AN IMPORTANT CONTRIBUTION TO THE DOCTRINE OF CEREBRAL LOCALIZATION. PMID- 17730102 TI - THE GREAT PRIMORDIAL FORCE. PMID- 17730103 TI - THE BOTANICAL OPPORTUNITY. PMID- 17730104 TI - PSYCHIATRY AND THE WAR. PMID- 17730106 TI - GEORGE FRANCIS ATKINSON. PMID- 17730105 TI - INTELLECTUAL INTERCOURSE BETWEEN ALLIED AND FRIENDLY COUNTRIES. PMID- 17730107 TI - ON SOME PROBOSCIDEANS OF THE STATE OF NEW YORK. PMID- 17730108 TI - HUMAN FLYING. PMID- 17730109 TI - KEEPING STEP. PMID- 17730110 TI - PRELIMINARY REPORT OF EXPERIMENTS ON THE ACTION OF DICHLOROETHYLSULFIDE (MUSTARD GAS) ON THE CELLS OF MARINE ORGANISMS. PMID- 17730111 TI - SPECIAL ARTICLES. PMID- 17730112 TI - Microphysiology. PMID- 17730113 TI - Publications Received. PMID- 17730114 TI - Meetings & Conferences. PMID- 17730115 TI - Comparative Anatomy, Embryology, and Histology Synthesized. PMID- 17730116 TI - Zoological Nomenclature. PMID- 17730117 TI - Passport Procedures. PMID- 17730118 TI - Scientific instrumentation. PMID- 17730119 TI - Probing the structure of the deep continental crust. AB - Old, buried, deformed, crystalline rocks apparently make up most of the 40 kilometer-thick continental crust. This part of the earth is poorly explored and constitutes a major frontier of modern earth science. Two techniques, seismic reflection profiling and drilling, which were developed by industry for other purposes, offer special potential for such exploration. Seismic profiling of the deep crust by COCORP (the Consortium for Continental Reflection Profiling) has already produced important information, including evidence for extensive thin skinned thrusting of older rocks over a continental margin as the corresponding ocean basin closed. Deep drilling of crystalline rocks of the continents for scientific purposes is so far relatively unexploited in the United States but is already being carried on elsewhere. In general, big science is likely to become more important in basic geology as this frontier is explored. PMID- 17730120 TI - The Senate's Plan for Nuclear Waste. PMID- 17730122 TI - France readies new research law. PMID- 17730123 TI - Reorienting CNRS. PMID- 17730121 TI - National academy of sciences elects new members. PMID- 17730124 TI - Slave labor on campus: the unpaid postdoc. PMID- 17730125 TI - Edwards Defends Budget Cuts at DOE. PMID- 17730126 TI - USDA Retreats on Gypsy Moth Front. PMID- 17730127 TI - NAS Calls for Arms Talks. PMID- 17730128 TI - GAO Points Up Military Use of Shuttle. PMID- 17730129 TI - Peace academy gaining momentum. PMID- 17730130 TI - Exploring plant resistance to insects. PMID- 17730131 TI - A concept of many uses. PMID- 17730132 TI - Archeological strategies. PMID- 17730133 TI - Invertebrate paleobiology. PMID- 17730134 TI - Color vision in vertebrates. PMID- 17730135 TI - Microscale patchiness of nutrients in plankton communities. AB - Autoradiography was used to identify the presence of nutrient patches produced by zooplankton. Algal cells which encounter patches of phosphorus-33 released by swimming animals accumulate more label than cells that do not enter the patches. Differential labeling of algae does not occur when turbulence in the fluid is increased by stirring. Nutrient patchiness at the scale of millimeters or less in nature probably influences the course of competition and coexistence among the phytoplankton. PMID- 17730136 TI - Aircraft monitoring of surface carbon dioxide exchange. AB - Aircraft-mounted sensors were used to measure the exchange of carbon dioxide above a cornfield, a forest, and a lake under midday conditions. Mean absorption values of 3400, 1200, and 100 milligrams of carbon dioxide per square meter per hour, respectively, are consistent with reported ground-based observations of carbon dioxide flux. Such information, gathered by aircraft, could be used to provide a quantitative evaluation of source and sink distributions of carbon dioxide in the biosphere, to establish a correlation between satellite data and near-surface measurements, and to monitor crop performance. PMID- 17730137 TI - Suppression of reflex postural tonus: a role of peripheral inhibition in insects. AB - Postural reflexes act through a single excitatory motoneuron of the several that innervate a flexor muscle of the cockroach leg. A peripheral inhibitory neuron whose axon accompanies this excitatory motoneuron is able to suppress muscle tensions developed from postural reflexes without affecting centrally generated muscle tensions. The inhibitory neuron could thus serve to rapidly suppress postural tensions at the initiation of escape. PMID- 17730138 TI - Is sperm cheap? Limited male fertility and female choice in the lemon tetra (pisces, characidae). AB - In the laboratory, fertilization rates achieved by male lemon tetras decline with spawning frequency. Even when the number of females is not limited, males can produce only four times as many offspring as females. Females show a preference for males that have not recently spawned as opposed to those that have. The cost of producing sufficient sperm to maximize fertilization rates may therefore reduce the intensity of sexual selection in this polygamous fish species. PMID- 17730139 TI - Global carbon monoxide fluxes: inappropriate measurement procedures. PMID- 17730141 TI - PRODUCTS and MATERIALS. PMID- 17730140 TI - Global carbon monoxide fluxes: inappropriate measurement procedures. PMID- 17730142 TI - SCIENCE AND MEDICINE. PMID- 17730143 TI - NEW YORK ACADEMY OF SCIENCES: REGULAR BUSINESS MEETING. PMID- 17730144 TI - SECTION OF GEOLOGY AND MINERALOGY. PMID- 17730146 TI - ON THE LIFE DURATION OF THE HETEROCERA (MOTHS*). PMID- 17730145 TI - SECTION OF CHEMISTRY. PMID- 17730147 TI - RETARDED DEVELOPMENT IN INSECTS. PMID- 17730149 TI - MECHANICAL SCIENCE. PMID- 17730148 TI - ELECTRIC RAILROADS IN PARIS. PMID- 17730151 TI - To the Editor of "Science". PMID- 17730150 TI - ANOTHER CONFIRMATION OF PREDICTION. PMID- 17730152 TI - Catastrophe theory: a skeptic. PMID- 17730153 TI - Modern agrarianism. PMID- 17730155 TI - Sociobiology and scientific debate. PMID- 17730154 TI - Interfering satellite. PMID- 17730156 TI - How fares basic science? PMID- 17730157 TI - The Mind's Eye: Nonverbal Thought in Technology. PMID- 17730158 TI - Ice Cream: Dairymen Imperiled by FDA's Recipe. PMID- 17730159 TI - New ADAMHA Head Expected to Lead, Not Just Coordinate. PMID- 17730161 TI - Woods hole mulls titanic expedition. PMID- 17730160 TI - Moratorium for the bowhead: eskimo whaling on ice? PMID- 17730162 TI - Congress may gut federal floodplains policy. PMID- 17730163 TI - Widespread PBB Contamination Can Affect Immune System. PMID- 17730164 TI - Erratum. AB - Frederick III, the grandfather of economist Oskar Morgenstern, was misidentified in the 12 August issue (p. 649). Frederick was King of Prussia and Emperor of Germany; he ruled briefly in 1888. PMID- 17730165 TI - Amorphous silicon: a new direction for semiconductors. PMID- 17730167 TI - Science studies in the u.s.s.R. PMID- 17730166 TI - Viral messenger structure: some surprising new developments. PMID- 17730168 TI - Ungulate ecology. PMID- 17730169 TI - Muscle research. PMID- 17730171 TI - Plant-animal mutualism: coevolution with dodo leads to near extinction of plant. AB - An endemic sapotaceous tree Calvaria major found on the island of Mauritius is nearly extinct because its seeds apparently required passage through the digestive tract of the now-extinct dodo Raphus cucullatus to overcome persistent seed coat dormancy caused by a specially thickened endocarp. PMID- 17730170 TI - Radioactive wastes: a comparison of u.s. Military and civilian inventories. AB - Contrary to widespread belief, the accumulated inventory of fission products generated by the still small U.S. civilian nuclear power industry may already be comparable to that generated in the past by U.S. military nuclear programs. Although the volumes of the military wastes are very large, they are on the average almost 100 times more dilute than projected commercial high-level wastes. PMID- 17730172 TI - Solar proton event: influence on stratospheric ozone. AB - Large-scale reductions in the ozone content of the middle and upper stratosphere over the polar cap regions were associated with the major solar proton event of 4 August 1972. This reduction, which was determined from measurements with the backscattered ultraviolet experiment on the Nimbus 4 satellite, is interpreted as being due to the catalytic destruction of ozone by odd-nitrogen compounds (NO(x)) produced by the event. PMID- 17730174 TI - A new satellite of saturn? AB - Analysis of all available observations of faint objects near Saturn during the 1966 passage of the earth through the plane of Saturn's rings suggests the existence of at least one previously undiscovered satellite of Saturn. The data support the previously published orbit for Janus. These satellites may be major members of an extended ring. PMID- 17730175 TI - PRODUCTS and MATERIALS. PMID- 17730173 TI - Carbon-13/carbon-12 ratio is relatively uniform among honeys. AB - The variability of the carbon-13/carbon-12 ratio in honeys was evaluated preliminary to use of the ratio to detect the addition of high-fructose corn syrup to honey. Eighty-four honey samples representing 34 states and including 37 floral types from 17 plant families were analyzed. The mean value of the per mil increment in carbon-13 (delta13C) for all samples is -25.2 per mil, and the coefficient of variation is 3.7 percent. This is the smallest variation yet encountered for a honey constituent or physical property. The range and magnitude of the values suggest that the floral sources are C(3) plants. PMID- 17730177 TI - Letters to the editor. PMID- 17730176 TI - Drosophila: tender loving care. PMID- 17730178 TI - If not grades, what criteria? PMID- 17730180 TI - LBJ's Last Budget: R&D Follows a "Status Quo" Pattern. PMID- 17730179 TI - Sonic booms from supersonic transport. PMID- 17730181 TI - Steam cars: jet tycoon, others, espouse the cause. PMID- 17730182 TI - TRACES: Basic Research Links to Technology Appraised. PMID- 17730183 TI - Suspended particulate matter: concentration in the major oceans. AB - Quantitative data from over 500 concentrates of suspended particulate material has been summarized statistically for the Atlantic, Pacific, and Indian oceans, the Gulf of Mexico, and the Caribbean Sea. From clear ocean water a majority of samples were in the range of 0 to 9.9 milligrams per 200 liters and the next largest number were in the range of 10 to 19.9 milligrams per 200 liters. Certain areas of cloudy or nepheloid water, observed photographically, contain relatively more samples in heavier concentration ranges and have larger mean values than clear ocean water. PMID- 17730184 TI - Fossil deep-sea channel on the aleutian abyssal plain. AB - The discovery of a leveed deep-sea channel whose axial gradient reverses near the Aleutian trench supports the hypothesis that the downbowing of the trench interrupted the turbidity current processes that constructed the Aleutian abyssal plain. PMID- 17730185 TI - Garnet-like structures of high-pressure cadmium germanate and calcium germanate. AB - Crystals of CdGeO(3) grown at a pressure of 65 kilobars are tetragonal and have an ordered, garnet-like crystal structure with cadmium occupying the dodecahedral and octahedral sites, and germanium the octahedral and tetrahedral sites. The crystal structure (a = 12.406 +/- 1 angstroms, c = 12.256 +/- 1 angstroms, and space group 14,/a) has been refined by least-squares analysis to an R (discrepancy index) of 0.073. Two high-pressure phases of CaGeO(3) were synthesized, one isotypic with tetragonal CdGeO(3) (a = 12.514 +/- 3 angstroms, c = 12.358 +/- 3 angstroms), and the other isotypic with perovskite. PMID- 17730186 TI - Pistillate papaya flower: a morphological anomaly. AB - The pistillate flower of Carica papaya is a pleurogynous unisexual form derived intraspecifically from a perigynous bisexual ancestor. It is a morphological anomaly in that the ovary consists of two cycles of carpels which, in the ancestor, arise on the receptacle at different levels as dissimilar orders of organs. The bulk of the pentamerous ovary and the dorsal carpellary vascular system are derived from a cycle of five stamens in the ancestor. The ventral carpellary system is inherited intact from the ancestor which has normal morphology in the sense that the carpels consist of a single cycle of sporophylls. PMID- 17730187 TI - RUBBER-PRODUCING PLANTS. PMID- 17730188 TI - THE PRESERVATION OF FORESTS. PMID- 17730189 TI - THE RESPIRATION FERMENT. PMID- 17730190 TI - REFRIGERATION FOR THE COOLING OF MINES. PMID- 17730191 TI - THE ERUPTION OF KILAUEA. PMID- 17730192 TI - THE CALIFORNIA EYE GNAT. PMID- 17730194 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17730195 TI - THE PLANETESIMAL HYPOTHESIS. PMID- 17730193 TI - PLEISTOCENE GLACIATIONS OF THE NORTHERN HEMISPHERE. PMID- 17730196 TI - EINSTEIN'S APPRECIATION OF SIMON NEWCOMB. PMID- 17730197 TI - EULER'S TENSOR AND HAMILTON'S CUBIC. PMID- 17730198 TI - AN IMPROVED METHOD OF PALM-PRINTING. PMID- 17730200 TI - INTRANUCLEAR INCLUSIONS IN YELLOW FEVER. PMID- 17730199 TI - A DEVICE FOR MEASURING SURFACE TENSION AUTOMATICALLY. PMID- 17730201 TI - WILL THE ADULT FIREFLY LUMINESCE IF ITS LARVAL ORGANS ARE ENTIRELY REMOVED? PMID- 17730202 TI - PLASMOPARA MILDEW OF SUNFLOWER. PMID- 17730203 TI - Cranberry Smash. PMID- 17730204 TI - Science in the News. PMID- 17730205 TI - Molting of Preadult Nematodes of the Genus Paratylenchus Stimulated by Root Diffusates. AB - The nonfeeding preadult larvae of the plant-parasitic nematodes, Paratylenchus projectus and P. dianthus, survive in moist soil during long periods in the absence of host plants. In water, only small percentages molt to the adult stage. In root diffusates from some but not all plants, nearly all of them molt. PMID- 17730206 TI - MARIHUANA. PMID- 17730207 TI - THE ROYAL SOCIETY OF CANADA. PMID- 17730208 TI - INTER-AMERICAN SOCIETY OF MICROBIOLOGY. PMID- 17730209 TI - THE CONCILIUM BIBLIOGRAPHICUM. PMID- 17730210 TI - CHEMISTRY EXHIBITS OF THE CHICAGO MUSEUM OF SCIENCE AND INDUSTRY. PMID- 17730211 TI - THE LOS ANGELES MEETING OF THE AMERICAN INSTITUTE OF ELECTRICAL ENGINEERS. PMID- 17730212 TI - THE AMERICAN MINING CONGRESS. PMID- 17730214 TI - BACTERICIDAL FILTRATES FROM A MOLD CULTURE. PMID- 17730213 TI - ANTLER-EATING BY RODENTS. PMID- 17730215 TI - FIFTY HARVARD GRADUATES. PMID- 17730217 TI - THE NATIONAL RESEARCH COUNCIL COMMITTEE ON MATHEMATICAL TABLES AND AIDS TO COMPUTATION. PMID- 17730216 TI - THE EATING OF BONE BY SQUIRRELS. PMID- 17730218 TI - RADIO-IRON IN PLASMA DOES NOT EXCHANGE WITH HEMOGLOBIN IRON IN RED CELLS. PMID- 17730219 TI - VISCOSITY AND THE SHAPE OF PROTEIN MOLECULES. PMID- 17730220 TI - AN ELECTRONIC RELAY FOR HEAT CONTROL. PMID- 17730221 TI - INEXPENSIVE MICROPHOTOGRAPHIC RECORDS. PMID- 17730222 TI - Erratum. AB - In the report by A. Persechini and D. J. Hartshorne (18 Sept., p. 1383), the abscissa of the insert in Fig. 2 is labeled incorrectly. It should read "(32)P incorporation/kinase (microg/ml)." PMID- 17730223 TI - Hinged teeth. PMID- 17730225 TI - Support of scientific journals. PMID- 17730224 TI - Censorship charge. PMID- 17730226 TI - Acyclic stereocontrol through the aldol condensation. AB - For the scientist who wishes to synthesize complex organic compounds, the most difficult problem is often establishing the correct configuration at the various chiral centers as the synthesis is being carried out. In the past decade, there has been an increasing effort to find direct solutions to this problem, which is particularly acute in the synthesis of acyclic and other conformationally flexible molecules. One of the oldest organic reactions, the aldol condensation, is emerging as a powerful tool for use in achieving such stereocontrol. PMID- 17730227 TI - Prehistoric irrigation systems in the salt river valley, Arizona. AB - This article discusses prehistoric irrigation canals recently excavated near Phoenix, Arizona. The canals were constructed by the Hohokam Indians between A.D. 850 and 1450. Several aerial photographs taken at various times in the past five decades clearly show the paths of hundreds of the canals, including some of those recently excavated. These data provide new insights on Hohokam irrigation technology and society. Despite the destructive inroads of modern development, much significant archeological information can still be retrieved both by conventional excavation methods and by the archival study of aerial photographs. PMID- 17730229 TI - Reagan's Plan for Nuclear Power. PMID- 17730228 TI - Mit agonizes over links with research unit. PMID- 17730230 TI - No boost in sight for science budgets. PMID- 17730231 TI - Germplasm resources are losing ground. PMID- 17730232 TI - Arms Control Teach-ins Planned by Scientists. PMID- 17730233 TI - Senate gives blessing to baby bell. PMID- 17730234 TI - French discuss reviving 1968 university reforms. PMID- 17730235 TI - NIOSH Move Is Postponed. PMID- 17730236 TI - Whither the shoreline? PMID- 17730238 TI - Vertebrate morphology. PMID- 17730237 TI - Computing: key developments. PMID- 17730239 TI - Software. PMID- 17730240 TI - The space science program. PMID- 17730241 TI - Invertebrate eyes. PMID- 17730242 TI - Mechanisms of nitrogen dioxide reactions: initiation of lipid peroxidation and the production of nitrous Acid. AB - The reactions of nitrogen dioxide with cyclohexene have been studied as a model for the reactions that occur between nitrogen dioxide in smoggy air and unsaturated fatty acids in pulmonary lipids. As predicted from earlier studies at high nitrogen dioxide concentrations, this gas reacts with cyclohexene predominantly by addition to the double bond at nitrogen dioxide concentrations of 1 percent (10,000 parts per million) to 40 percent in nitrogen; in the presence of air or oxygen, this reaction initiates the autoxidation of the alkene. However, at concentrations below 100 parts per million in nitrogen, nitrogen dioxide reacts with cyclohexene almost exclusively by abstraction of allylic hydrogen; this unexpected reaction also initiates the autoxidation of the alkene in the presence of oxygen or air, but it leads to the production of nitrous acid rather than of a product containing a nitro group attached to a carbon atom. The nitrous acid can react with amines to produce nitrosamines. Moreover, the nitrite ion produced by the hydrogen abstraction mechanism would be expected to diffuse throughout the body, unlike nitrated lipids that would be confined to the pulmonary cavity. These findings have been confirmed with methyl oleate, linoleate, and linolenate; some of the kinetic features of the nitrogen dioxide-initiated autoxidation of these unsaturated fatty acids have been studied. PMID- 17730243 TI - Mechanism of single-layer graphite oxidation: evaluation by electron microscopy. AB - Etch-decoration reveals that the rate of removal of carbon atoms exposed at monolayer steps on graphite surfaces depends on the population density of these edge atoms (the rate is higher at a low-density surface) and that carbon removal continues for a prolonged period after the oxygen supply in the gas phase has been shut off. The edge carbons are removed by both oxygen from the gas phase and oxygen in the adsorbed oxides which migrate from the neighboring basal carbon atoms. PMID- 17730244 TI - Oxygen Deficiency in Spartina alterniflora Roots: Metabolic Adaptation to Anoxia. AB - The aerenchyma (air-space) tissue in the wetland macrophyte Spartina alterniflora conveys sufficient oxygen to roots for predominately aerobic respiration in moderately, but not highly, reduced substrates. Continuously flooded plants survive by respiring anaerobically, although growth is decreased. Two metabolic adaptations to flooding are displayed in this species, depending on the degree of soil reduction. PMID- 17730245 TI - Metals in estuarine sediments: factor analysis and its environmental significance. AB - Q-mode factor analysis has been used to partition the variability of environmentally active metals in Delaware Bay sediments. Three factors, identified as a natural background source, an oceanic or seawater source, and an estuarine source, account for 96 percent of the metal variability. PMID- 17730246 TI - Epifluorescence and video analysis of vacuole motility and development in stomatal cells of allium. AB - The vacuole in stomatal cells of Allium undergoes major changes in shape during differentiation, switching from a globular form in new guard mother cells to a network of interconnected tubules and chambers, and then back to a globular form as guard cells mature. In addition, vacuolar network elements exhibit characteristic movements and rearrangements. PMID- 17730247 TI - Interaction Between the Antibiotic Trichothecenes and the Higher Plant Baccharis megapotamica. AB - The Brazilian shrub Baccharis megapotamica contains significant amounts of antibiotic trichothecenes. When these plants are grown in the United States, they are devoid of the mycotoxins. Feeding experiments with fungus-produced trichothecenes show that Baccharis megapotamica absorbs, translocates, and chemically alters these compounds to ones with structures analogous to those found in the plant in its native habitat. The mycotoxins, which have no apparent ill effect in Baccharis megapotamica, kill tomatoes, peppers, and artichokes. PMID- 17730248 TI - Vibratory communication through living plants by a tropical wandering spider. AB - Female Cupiennius salei pheromone on banana and Agave plants elicits patterned oscillations by the male. Resulting pulse trains of vibrations through the leaf average 76 hertz. The brief vibratory response by the otherwise immobile female hidden up to at least 1 meter away on another leaf guides the male across the plant to her location. Reciprocal signaling continues in the presence of random noise that masks the male's airborne sounds. PMID- 17730250 TI - PRODUCTS and MATERIALS. PMID- 17730249 TI - Questions about spatial adaptation of short-wavelength pathways in humans. PMID- 17730252 TI - Meetings & Conferences. PMID- 17730251 TI - Operations Diagnosis in Research Planning. PMID- 17730253 TI - White Mountain High Altitude Research Station. PMID- 17730255 TI - Shipping Small Animals. PMID- 17730254 TI - Eugene Curtis Auchter: 1889-1952. PMID- 17730256 TI - THE TUBERCULIN TEST. PMID- 17730257 TI - THE ORGANISM CAUSING CANCER. PMID- 17730258 TI - A NEW DEWBERRY. PMID- 17730260 TI - THE THIRD PAN-PACIFIC SCIENCE CONGRESS. PMID- 17730259 TI - SOME MATHEMATICAL ASPECTS OF COSMOLOGY. PMID- 17730261 TI - THE ART OF PLUVICULTURE. PMID- 17730262 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17730263 TI - A ROOT ROT OF ALFALFA. PMID- 17730264 TI - THE DEFINITION OF LOESS. PMID- 17730265 TI - A SIMPLIFIED RAINPROOF VALVE FOR POROUS PORCELAIN ATMOMETERS. PMID- 17730266 TI - THE PHOTOCHEMISTRY OF COD LIVER OIL. PMID- 17730267 TI - "RUSSELL EFFECT," NOT ULTRAVIOLET LIGHT, RESPONSIBLE FOR CHANGES PRODUCED IN THE PHOTOGRAPHIC PLATE BY ANTIRACHITIC SUBSTANCES. PMID- 17730268 TI - DIVISION OF CHEMICAL EDUCATION. PMID- 17730269 TI - COSMIC CLOUDS. PMID- 17730270 TI - AFRICA AND SCIENCE. PMID- 17730271 TI - THE TRANSFER OF SKILL AND THE EMOTIONS. PMID- 17730272 TI - PROSPERITY AND THE SURVIVAL OF SPECIES. PMID- 17730273 TI - PREHISTORIC RELICS OF SOUTH AFRICA. PMID- 17730274 TI - CHEMISTRY AS AN AID TO BIOLOGY. PMID- 17730275 TI - SOME PROBLEMS OF COSMICAL PHYSICS, SOLVED AND UNSOLVED. AB - The Great success of theoretical investigations in recent times naturally leads enterprising spirits to use them not only in interpreting what we know or can verify by observation, but to lead us into regions where experiment is not available as a check. I believe that this does nothing but good in times like ours, when there is no danger of the doctrines even of a master being unduly pressed, if the evidence of observed fact turns against them. At the same time, we must not expect too much of pure intellect unchecked by observation. Theories that do not stand the test of time pass for the most part into complete oblivion, and we are apt to forget how appallingly large a mass of wreekage the total of them represents. The next generation remembers chiefly those that survive, and does not take full advantage of the lesson of how easy it is for an apparently inevitable conslusion to be wrong. Unless the argument carried its own verification by some accurate and previously unforeseen numerical coincidence, it is hard indeed to tell if we are on the right track. PMID- 17730277 TI - OBITUARY. PMID- 17730276 TI - THE DECLINE IN THE AVERAGE LENGTH OF LIFE. PMID- 17730278 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17730280 TI - DID JOHN NAPIER INVENT LOGARITHMS? PMID- 17730279 TI - PRIORITY IN STRATIGRAPHIC NOMENCLATURE. PMID- 17730281 TI - LACTATION VS. IMPROVED GROWTH IN STOCK ALBINO RATS. PMID- 17730282 TI - DINOSAUR TENDONS. PMID- 17730283 TI - STANFORD UNIVERSITY SCIENTIFIC EXPEDITION. PMID- 17730284 TI - CHEMICAL TREATMENT TO SHORTEN THE REST PERIOD OF SUGAR MAPLE TREES. PMID- 17730285 TI - ON THE INCIDENCE OF INFECTION WITH INTESTINAL PROTOZOA. PMID- 17730286 TI - Survey of Physiological Science. PMID- 17730287 TI - Meetings & Conferences. PMID- 17730288 TI - Integrated Enzyme Activity in Soluble Extracts of Heart Muscle. PMID- 17730289 TI - Thermal Stimulation of Isolated Organs and its Inhibition by Pharmacological Agents. PMID- 17730290 TI - Effects of an Exogenous Growth Regulator on Proteolytic Enzymes of the Soybean Plant. PMID- 17730291 TI - Repeated Semiannual Spawning of Northern Oysters. PMID- 17730292 TI - Chlorogenic Acid a Possible Metabolite in the Terminal Oxidase System of the White Potato. PMID- 17730293 TI - Enzymatic Reduction of Cystine by Coenzyme I (DPNH). PMID- 17730295 TI - Veralbidine, a New Alkaloid from Veratrum album. PMID- 17730294 TI - The Effect of Experimental Stress upon the Photically Activated EEG. PMID- 17730296 TI - Melting Phenomena of a Surface of Monomolecular Thickness. PMID- 17730298 TI - Zoological Nomenclature. PMID- 17730297 TI - Salivary Amylase Inhibition. PMID- 17730299 TI - Experts' Biases about the Older Worker. PMID- 17730300 TI - Isolation of Ascorbic Acid and Rhamnosides from Sea Water. PMID- 17730302 TI - JEAN ALBERT GAUDRY. PMID- 17730301 TI - EARTHQUAKE FORECASTS INTRODUCTION. PMID- 17730303 TI - PECULIAR ELECTRICAL PHENOMENA. PMID- 17730305 TI - BOTANICAL NOTES. PMID- 17730304 TI - RAILROAD RATES FOR THE BALTIMORE MEETING. PMID- 17730306 TI - SOME REMARKS ON THE CULTURE OF EASTERN NEAR-ARCTIC INDIANS. PMID- 17730308 TI - This week in science. PMID- 17730307 TI - SECTION A--MATHEMATICS AND ASTRONOMY. PMID- 17730309 TI - Response: the core curriculum. PMID- 17730311 TI - The core curriculum. PMID- 17730310 TI - The core curriculum. PMID- 17730312 TI - The core curriculum. PMID- 17730314 TI - Erratum. AB - In the article "Space station price climbs higher" by Eliot Marshall (News & Comment, 17 July, p. 242), Herbert Friedman, a member of the National Research Council panel studying the space station, was incorrectly identified as a former presidential economic adviser. He is emeritus scientist, Naval Research Laboratory and Martin Marietta Fellow of the National Air and Space Museum. PMID- 17730313 TI - The core curriculum. PMID- 17730315 TI - Strains in U. S.--Japan Exchanges: American complain that Japan has not reciprocated in transferring technology, as the Japanese open the door slowly. PMID- 17730316 TI - Stumbling on superconductors. PMID- 17730317 TI - Soviet research to be self-directed. PMID- 17730318 TI - SDI Testing May Ignite Antisatellite Race. PMID- 17730319 TI - Artificial Intelligence Moves into Mainstream: For software developers, the most important result of this research may not be the AI programs at all, but the AI programming style. PMID- 17730321 TI - Scientific basis of modern weather prediction. PMID- 17730320 TI - Search for a new exchange-rate regime. AB - The regime of unmanaged floating exchange rates was implicitly judged a failure when, with the Plaza Agreement, attempts at cooperative exchange-rate management were reintroduced primarily because of concern at the size of misalignments. Any satisfactory successor regime will need to limit misalignments while retaining the genuine social benefits of exchange-rate flexibility. It is argued that a system of target zones for exchange rates, ideally embedded in a more comprehensive set of guidelines for international economic policy coordination, could best reconcile these needs. PMID- 17730322 TI - Limits on sensitivity of large silicon bolometers for solar neutrino detection. AB - Estimates are given for ultimate limits on background in proposed direct-counting measurements of neutrino scattering from large silicon crystals. Methods of background reduction are discussed. In the best case, the limiting backgrounds due to activities from cosmic-ray spallation of silicon would be less than the expected true event rate for reactor neutrino measurements of coherent neutral current scattering from silicon nuclei. Considerable reduction of the estimated high-energy backgrounds would be required for a good signal-to-noise ratio in solar neutrino detection. PMID- 17730323 TI - Bacterial Methanogenesis and Growth from CO2 with Elemental Iron as the Sole Source of Electrons. AB - Previous studies of anaerobic biocorrosion have suggested that microbial sulfur and phosphorus products as well as cathodic hydrogen consumption may accelerate anaerobic metal oxidation. Methanogenic bacteria, which normally use molecular hydrogen (H(2)) and carbon dioxide (CO(2)) to produce methane (CH(4)) and which are major inhabitants of most anaerobic ecosystems, use either pure elemental iron (Fe(0)) or iron in mild steel as a source of electrons in the reduction of CO(2) to CH(4). These bacteria use Fe(0) oxidation for energy generation and growth. The mechanism of Fe(0) oxidation is cathodic depolarization, in which electrons from Fe(0) and H(+) from water produce H(2), which is then released for use by the methanogens; thermodynamic calculations show that significant Fe(0) oxidation will not occur in the absence of H(2) consumption by the methanogens. The data suggest that methanogens can be significant contributors to the corrosion of iron-containing materials in anaerobic environments. PMID- 17730324 TI - Improved orbital and physical parameters for the pluto-charon system. AB - Analysis of the observations of several Pluto-Charon occultation and transit events in 1985 and 1986 has provided a more detailed knowledge of the system. The sum of the radii of Pluto and Charon is 1786 +/- 19 kilometers, but the individual radii are somewhat more poorly determined; Pluto is 1145 +/- 46 kilometers in radius and Charon is 642 +/- 34 kilometers in radius. The mean density of the system is 1.84 +/- 0.19 grams per cubic centimeter, implying that more than half of the mass is due to rock. Charon appears to have hemispheres of two different colors, the Plutofacing side being neutral in color and the opposite hemisphere being a reddish color similar to Pluto. PMID- 17730325 TI - An invariance in the isoheptanes of petroleum. AB - Four isoheptanes in petroleum display a remarkable invariance in a ratio of sums of concentrations. The isoheptanes are not at thermodynamic equilibrium, nor are they fixed to some constant composition. The four isomers display coherent change in relative amounts but maintain invariance in the ratio of sums. Within sets of genetically related petroleum samples, invariance reaches levels that approach the limits of our analytical precision. The invariance is inconsistent with a chemical origin that involves the thermal fragmentation of natural products or their derivatives. It suggests a reaction process at steady state, in which relative rates of product formation are constant. A mechanism is proposed in which the four isoheptanes are formed pairwise and sequentially through two intermediates in a catalytic process that operates at steady state. PMID- 17730327 TI - The Second Anua1 AAAS Colloquium on Science, Arms Control, and National Security: Science & Security: Nuclear and Conventional Forces in Europe. PMID- 17730326 TI - Response: asymmetry of neural feedback in the organizaton of behavioral States. PMID- 17730328 TI - A leader in biomedical science: walter B. Cannon. PMID- 17730330 TI - Early epidemiology: yellow Fever in the north. PMID- 17730329 TI - Marine mycology: the biology of marine fungi. PMID- 17730331 TI - Sensory physiology: visual neuroscience. PMID- 17730332 TI - COMMENT AND CRITICISM. PMID- 17730333 TI - THE EUROPEAN COLONIES AND THEIR TRADE. PMID- 17730334 TI - THE U. S. GEOLOGICAL SURVEY. PMID- 17730335 TI - THE RAILWAY TO CENTRAL ASIA. PMID- 17730336 TI - THE HUDSON BAY ROUTE TO EUROPE. PMID- 17730338 TI - THE PANAMA CANAL. PMID- 17730337 TI - PHOTOGRAPHIC STUDY OF STELLAR SPECTRA. PMID- 17730339 TI - LONDON LETTER. PMID- 17730340 TI - VIENNA LETTER. PMID- 17730341 TI - Certain questions relating to national endowment of research in this country, and their importance. PMID- 17730342 TI - Reports of the National academy of sciences. PMID- 17730344 TI - The silver problem. PMID- 17730345 TI - LABORATORY INSTRUCTION IN PHYSICS. PMID- 17730343 TI - A swindler abroad again. PMID- 17730346 TI - A NEW METHOD OF CHILD STUDY. PMID- 17730347 TI - JAPANESE NURSERY NOTES. PMID- 17730348 TI - SOME NOTES ON LIGHTHOUSE APPARATUS. PMID- 17730349 TI - EVIDENCE OF TWO PRE-MORAINIC GLACIAL MOVEMENTS. PMID- 17730350 TI - ELECTRICAL NOTES. PMID- 17730352 TI - Where is the Litre ? PMID- 17730351 TI - A JAPANESE SICK WITH SCARLET-FEVER. PMID- 17730353 TI - Low Temperatures. PMID- 17730355 TI - A New Source of the So-Called Mexican Onyx. PMID- 17730354 TI - On the Teaching of Biology. PMID- 17730356 TI - CONSTRUCTIVE SCIENTIFIC RESEARCH BY COOPERATION. PMID- 17730358 TI - THE ATTAINMENT OF HIGH LEVELS IN THE ATMOSPHERE. PMID- 17730357 TI - SUGGESTIONS FOR ECOLOGIC INVESTIGATIONS IN VERTEBRATE ZOOLOGY. PMID- 17730359 TI - THE SEPARATION OF THE ELEMENT CHLORINE INTO CHLORINE AND META-CHLORINE. PMID- 17730360 TI - WILHELM PFEFFER. PMID- 17730361 TI - HOW DID DARWIN WORK? PMID- 17730362 TI - IONIZATION AND RADIATION. PMID- 17730364 TI - A CONVENIENT DEMONSTRATION MOUNTING FOR JELLYFISHES. PMID- 17730363 TI - ORGANIZATION OF THE AMERICAN GEOPHYSICAL UNION. PMID- 17730365 TI - THE WESTERN SOCIETY OF NATURALISTS. PMID- 17730366 TI - IS UNPALATABLE FOOD PROPERLY DIGESTED? PMID- 17730367 TI - THE AMERICAN MATHEMATICAL SOCIETY. PMID- 17730368 TI - COMMENT AND CRITICISM. PMID- 17730370 TI - Photographs of the interior of a coal-mine. PMID- 17730371 TI - Points on lightning-rods. PMID- 17730369 TI - The initiation of deep-sea dredging. PMID- 17730372 TI - The 'bassalian fauna;' 'Pentacrinus asteriscus.'. PMID- 17730373 TI - ELECTRICAL TESTING ESTABLISHMENTS. PMID- 17730375 TI - BRITISH ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17730376 TI - This week in science. PMID- 17730374 TI - AMERICAN APPLIANCES FOR DEEP-SEA INVESTIGATION.--TRAWLS AND TANGLES. PMID- 17730377 TI - Educating the best and employing them. PMID- 17730378 TI - Ordering systems. PMID- 17730379 TI - Corrections and clarifications. AB - In the article "Genetic testing set for takeoff" by Rachel Nowak (News & Comment, 22 July, p. 464), Helix was cited as the source of information for the accompanying table describing genetic testing (p. 466). The information in the table regarding mutational mechanism, cost, and market size came from sources identified by Helix who were contacted separately. PMID- 17730381 TI - Sciencescope. PMID- 17730380 TI - Ordering systems. PMID- 17730382 TI - Britain takes first step in ph.d. Reform. PMID- 17730383 TI - Is the Fix in on Fermat's Last Theorem? PMID- 17730384 TI - Playing Hide-and-Seek With a Pulsar. PMID- 17730385 TI - Dino embryo recasts parents' image. PMID- 17730386 TI - Putting X-ray Lasers on the Table. PMID- 17730387 TI - Clashing maya superpowers emerge from a new analysis. PMID- 17730389 TI - Scientific resource center closes. PMID- 17730388 TI - Lighting up new genes. PMID- 17730390 TI - NSF Grant Boosts Telescope Plan. PMID- 17730391 TI - Finding the hottest dwarf. PMID- 17730392 TI - Producing the finest scientists and engineers for the 21st century. PMID- 17730393 TI - European union: fresh tracks for academic exchanges. PMID- 17730394 TI - Ecological character displacement. PMID- 17730395 TI - Nature of stress on the atomic level in dense polymer systems. AB - Stress in dense polymer systems is classically viewed as being molecular in character and is based on the entropic spring concept. A description on the atomic level has been developed on the basis of extensive computer simulations. An important new concept is the intrinsic monomer stress (IMS), the individual monomer contribution to the macroscopic stress referred to a local moving coordinate system in which the backbone bonds attached to that monomer are fixed. The IMS is time-independent and, for a given polymer system at fixed density, has the same value in the equilibrium melt, with the melt undergoing stress relaxation, and in the deformed cross-linked system. PMID- 17730396 TI - Fragmentation and flow regulation of river systems in the northern third of the world. AB - Seventy-seven percent of the total water discharge of the 139 largest river systems in North America north of Mexico, in Europe, and in the republics of the former Soviet Union is strongly or moderately affected by fragmentation of the river channels by dams and by water regulation resulting from reservoir operation, interbasin diversion, and irrigation. The remaining free-flowing large river systems are relatively small and nearly all situated in the far north, as are the 59 medium-sized river systems of Norway, Sweden, Finland, and Denmark. These conditions indicate that many types of river ecosystems have been lost and that the populations of many riverine species have become highly fragmented. To improve the conservation of biodiversity and the sustainable use of biological resources, immediate action is called for to create an international preservation network of free-flowing river systems and to rehabilitate exploited rivers in areas that lack unaffected watercourses. PMID- 17730397 TI - Use of taylor-aris dispersion for measurement of a solute diffusion coefficient in thin capillaries. AB - A method for the fast measurement of the diffusion coefficients of both small and large molecules in thin capillaries is reported. The method relies on Taylor-Aris dispersion theory and uses standard instrumentation for capillary zone electrophoresis. With this equipment, which consists of thin capillaries (50 to 100 micrometers in inner diameter), an injection system, detector ports, and computer data acquisition, a sample plug is pumped through the capillary at known velocity and the peak dispersion coefficient (D(*)) is measured. With the experimentally measured values of D(*) and flow velocity, and knowledge of the inner diameter of the capillary, the molecular diffusion coefficient (D) can be rapidly derived. For example, for ovalbumin a D value of 0.759 x 10(-6) square centimeter per second is found versus a tabulated value of 0.776 x 10(-6) square centimeter per second (error, 2 percent). For hemoglobin a D value of 0.676 x 10( 6) square centimeter per second is obtained versus a literature value of 0.690 x 10(-6) square centimeter per second (error, 1.5 percent). PMID- 17730398 TI - A theropod dinosaur embryo and the affinities of the flaming cliffs dinosaur eggs. AB - An embryonic skeleton of a nonavian theropod dinosaur was found preserved in an egg from Upper Cretaceous rocks in the Gobi Desert of Mongolia. Cranial features identify the embryo as a member of Oviraptoridae. Two embryo-sized skulls of dromaeosaurids, similar to that of Velociraptor, were also recovered in the nest. The eggshell microstructure is similar to that of ratite birds and is of a type common in the Djadokhta Formation at the Flaming Cliffs (Bayn Dzak). Discovery of a nest of such eggs at the Flaming Cliffs in 1923, beneath the Oviraptor philoceratops holotype, suggests that this dinosaur may have been a brooding adult. PMID- 17730399 TI - Autumn bloom of antarctic pack-ice algae. AB - An autumn bloom of sea-ice algae was observed from February to June of 1992 within the upper 0.4 meter of multiyear ice in the Western Weddell Sea, Antarctica. The bloom was reliant on the freezing of porous areas within the ice that initiated a vertical exchange of nutrient-depleted brine with nutrient-rich seawater. This replenishment of nutrients to the algal community allowed the net production of 1760 milligrams of carbon and 200 milligrams of nitrogen per square meter of ice. The location of this autumn bloom is unlike that of spring blooms previously observed in both polar regions. PMID- 17730400 TI - Experimental evidence that competition promotes divergence in adaptive radiation. AB - Interspecific competition driving divergence in adaptive radiation has not previously been tested experimentally. Natural selection on a morphologically variable species of stickleback fish was contrasted in the presence and absence of a close relative. Selection was nondirectional when the target species was alone, whereas addition of the second species favored individuals most different from it morphologically and ecologically. Disproportionately severe competition between similar phenotypes indicates frequency-dependent selection, verifying a crucial element of theory of competition and character divergence. The findings help resolve outstanding debates on the ecological causes of diversification and the evolutionary consequences of competitive interactions. PMID- 17730401 TI - Isolation of Virus Capable of Lysing the Brown Tide Microalga, Aureococcus anophagefferens. AB - Viruses have been hypothesized to control blooms of Aureococcus anophagefferens gen. et sp. nov. (Chrysophyceae), a marine phytoplankton that since 1985 has caused devastating summer blooms called "brown tide." By means of ultrafiltration methods, viruses specific to this alga were isolated from both the Great South Bay and Peconic Bay systems of Long Island, New York, during the summer bloom period of 1992. Cell lysis of healthy algal cultures was demonstrated, as well as continuing reinfection with serial transfers of cultures. Electron microscope surveys yielded images of phage-like virus particles with tails that could attach to A. anophagefferens cells within minutes of exposure. The isolation and cultivation of this virus highlights the need for further study of viral infection of eukaryotic algae and the potential for a better understanding of algal bloom control by viral infection. PMID- 17730402 TI - Response. PMID- 17730404 TI - Acculturation to science. PMID- 17730403 TI - The fortunes of an ideal. PMID- 17730406 TI - Products & materials. PMID- 17730405 TI - Vignettes: studying science. PMID- 17730407 TI - Coping with the underprepared undergraduate. PMID- 17730408 TI - Some small schools are big on manufacturing scientists. PMID- 17730409 TI - Assault on the lesson plan. PMID- 17730410 TI - Novel Program III: Undergraduate Nanotechnology. PMID- 17730411 TI - Novel Program IV: Commercializing Research. PMID- 17730412 TI - Novel Course III: Undergrad Labs "Get Real". PMID- 17730413 TI - Novel Course II: 21st-Century Chemistry. PMID- 17730414 TI - Novel Course IV: Survival Skills 101. PMID- 17730415 TI - Reader feedback. PMID- 17730417 TI - Harvard succeeds in the teaching of teachers. PMID- 17730416 TI - New modes for making scientists. PMID- 17730418 TI - Rewards--at Last--for Top Teachers. PMID- 17730420 TI - Stephen thompson: call him czar of small-scale chemistry. PMID- 17730419 TI - Ocean engineering? New wave in teaching marine biology. PMID- 17730421 TI - Why Eric Mazur Brings Chaos--Not Chaos Theory--to Physics. PMID- 17730422 TI - Turning students on by simulating the arcane. PMID- 17730423 TI - INTELLIGENT CITIZENSHIP. PMID- 17730425 TI - SCIENTIFIC NEWS IN WASHINGTON. PMID- 17730424 TI - Iroquois Mythology. PMID- 17730426 TI - Models of the Ocean's Bed. PMID- 17730428 TI - Onondaga White-Dog Feast. PMID- 17730427 TI - ELECTRICAL SCIENCE. PMID- 17730429 TI - SCIENCE NEWS. PMID- 17730430 TI - HIS PLACE IN GEOLOGICAL SCIENCE AND HIS CONTRIBUTIONS TO THE GEOLOGY OF NORTH AMERICA. PMID- 17730431 TI - THE CHEMICAL NATURE OF ENZYMES. PMID- 17730433 TI - REDWOODS AND FROST. PMID- 17730434 TI - THE SECOND PSYCHOLOGICAL EXPEDITION TO CENTRAL ASIA. PMID- 17730432 TI - STUDIES ON THE BOTTOM FAUNA OF FRESH-WATER LAKES. PMID- 17730436 TI - THE MEASUREMENT OF SKIN COLOR. PMID- 17730435 TI - NOMENCLATURE OF THE ELECTRON. PMID- 17730437 TI - PREPARING QUICK-DRYING CANADA BALSAM. PMID- 17730438 TI - BACTERIA AS FOOD FOR VERTEBRATES. PMID- 17730439 TI - LOCALIZATION OF SPIROCHETA PALLIDA IN THE BRAINS OF RABBITS FOLLOWING INTRASPINAL INJECTION OF TESTICULAR TISSUE AND PHYSIOLOGICAL SALT SOLUTION. PMID- 17730440 TI - AUDUBON AND HIS JOURNALS. PMID- 17730442 TI - MULTIPLE-CYLINDER STEAM-ENGINE. PMID- 17730441 TI - THE IMPORT OF THE TOTEM. PMID- 17730443 TI - PREHISTORIC QUARTZITE QUARRIES IN CENTRAL EASTERN WYOMING. PMID- 17730444 TI - ASSOCIATION OF AMERICAN ANATOMISTS. PMID- 17730445 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17730447 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17730446 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17730448 TI - DISCUSSION AND CORRESPONDENCE. PMID- 17730449 TI - SCIENTIFIC JOURNALS. PMID- 17730450 TI - New Directions in Research Support. PMID- 17730451 TI - R. W. Marriott, Astronomer. PMID- 17730452 TI - News of Science. PMID- 17730454 TI - On the Rule for Leap Year. PMID- 17730453 TI - Reagent for Differentiation of 1,4- and 1,6-Linked Glucosaccharides. PMID- 17730456 TI - Miscellaneous Publications. PMID- 17730455 TI - What Are Variables and Constants? PMID- 17730457 TI - Scientific Meetings. PMID- 17730458 TI - THE VISITORS TO ONE OAK TREE. PMID- 17730459 TI - THE USE OF TUBERCULIN AND MALLEIN FOR THE DIAGNOSIS OF TUBERCULOSIS AND GLANDERS IN ANIMALS. PMID- 17730460 TI - MENTAL IMAGES. PMID- 17730462 TI - CONSCIOUSNESS UNDER THE INFLUENCE OF CANNABIS INDICA. PMID- 17730461 TI - INMUNITY AND CURE IN THE INFECTIOUS DISEASES. PMID- 17730464 TI - THE RECENT DEVELOPMENT OF BIOLOGY. PMID- 17730463 TI - SCIENCE IN THE SCHOOLS.--A REPLY. PMID- 17730465 TI - THE PROBLEMS OF EXPERIMENTAL PSYCHOLOGY. PMID- 17730467 TI - 'BERYLLIUM' OR 'GLUCINUM.'. PMID- 17730466 TI - STYLE IN SCIENTIFIC COMPOSITION. PMID- 17730468 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17730470 TI - THE AMERICAN SOCIETY OF VERTEBRATE PALEONTOLOGISTS. PMID- 17730471 TI - THE TOTAL ECLIPSE OF SEPTEMBER 9, 1904. PMID- 17730469 TI - GOSSIP ABOUT LAMARCK. PMID- 17730472 TI - THE AMERICAN SOCIETY OF NATURALISTS. PMID- 17730475 TI - JOINT HEARINGS IN THE CONGRESS ON SCIENCE BILLS. PMID- 17730474 TI - FRANCIS BERTODY SUMNER August 1, 1874-September 6, 1945. PMID- 17730473 TI - SOIL MICROBIOLOGY AS A FIELD OF SCIENCE. AB - It can now be definitely recognized that the soil microbiologist is in a position to make important contributions not only to our knowledge of soil processes and plant growth, but also to microbiology, especially microbial physiology, and to the utilization of microorganisms for various industrial, public health and other processes. The soil microbiologist is able to contribute in many ways to man's capacity to survive, by learning to control the activities of injurious microorganisms and by favoring the processes brought about by the beneficial organisms. The reason why the broader concept "microbiology" rather than the narrower term "bacteriology" has been used throughout this discussion is that the soil microbiologist has often to pay as much attention to the fungi as to the bacteria, and occasionally also to the protozoa, the algae and even the nematodes and other worms, inhabiting the soil in large numbers. Only a recognition of all these lower forms of life and their many interrelationships can help to elucidate this complex and important science. PMID- 17730476 TI - THE JOHN SCOTT AWARD. PMID- 17730477 TI - FELLOWSHIPS OFFERED BY THE EASTMAN KODAK COMPANY. PMID- 17730478 TI - NEWS FROM ABROAD. PMID- 17730479 TI - SUSCEPTIBILITY OF THE YOUNG WHITE MOUSE (MUS MUSCULUS) TO EXPERIMENTAL LEPTOSPIROSIS. AB - The failure of even special methods to induce infection indicates that not all strains of young white laboratory mice (Mus musculus) are uniformly susceptible to fatal infection with Leptospira icterohemorrhagiae. Some strains of this species develop early pathological changes characteristic of the infection and harbor the organism in their kidneys, but do not succumb. Therefore not all strains of white mice are suitable for use in the diagnostic mouse protection test for leptospirosis described by Larson. PMID- 17730480 TI - THE EFFECT OF SODIUM CHLORIDE BALANCE ON THE AVIDITY OF ISOHEMAGGLUTININS. AB - (1) The avidity of agglutinins in human anti-A and anti-B serums is influenced by the tonicity of the menstruum. (2) The addition of sodium chloride in final concentration in a range of 1.45 to 1.75 per cent. will greatly increase the avidity of human serum isohemagglutinins. The author wishes to gratefully acknowledge the suggestion of Captain John Elliott (U.S.A.Sn.C.), that the restoration with hypertonic saline solution be investigated. PMID- 17730481 TI - IDENTIFICATION OF THE INHIBITORY FACTOR OF RETICULO-ENDOTHELIAL IMMUNE SERUM (REIS) IN A GLOBULIN FRACTION. PMID- 17730483 TI - SOVIET BIOLOGY. PMID- 17730482 TI - CONTROL AND EVALUATION OF BLOOD SERUM ASSAYS FOR PENICILLIN. AB - A method for adequate control and evaluation of blood serum assays for penicillin is given and the effectiveness of the method for controlling the several types of penicillin is shown. PMID- 17730485 TI - ON THE FORMATION OF ACETYLCHOLINE IN THE NERVE AXON. PMID- 17730484 TI - AMYLASE INHIBITOR OF NAVY BEANS. PMID- 17730486 TI - SCIENCE NEWS. PMID- 17730487 TI - THE BIOLOGIC ASPECTS OF HAY FEVER AND ASTHMA. PMID- 17730488 TI - EDGAR FAHS SMITH. PMID- 17730490 TI - AN IMPORTANT SOURCE OF BROAD TAPEWORM IN AMERICA. PMID- 17730489 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17730491 TI - THE HEREDISCOPE AND ARTIFICIAL POPULATIONS. PMID- 17730492 TI - THE WORD TO REPLACE "BELIEVE". PMID- 17730493 TI - HYBRID WORDS. PMID- 17730494 TI - PRESERVATION OF THE HEATH HEN. PMID- 17730495 TI - BIRDS OF THE EURASIAN TUNDRA. PMID- 17730496 TI - BIOCHEMICAL EXPERIMENTS PRACTICAL FOR ELEMENTARY BIOLOGY CLASSES. PMID- 17730497 TI - ASSOCIATION OF THE CAUSATIVE AGENT OF A CHICKEN TUMOR WITH A PROTEIN FRACTION OF THE TUMOR FILTRATE. PMID- 17730498 TI - MARKING LIVING FISHES FOR EXPERIMENTAL PURPOSES. PMID- 17730499 TI - A "FOSSIL" CAMEL RECENTLY LIVING IN UTAH. PMID- 17730500 TI - Three mile island. PMID- 17730501 TI - Three mile island. PMID- 17730502 TI - Erratum. AB - The second author of the report "Immunocompetence in the lowest Metazoan phylum: Transplantation immunity in sponges" (27 Apr., p. 420) was Ian S. Johnston, not Johnson. PMID- 17730503 TI - "Strategy". PMID- 17730505 TI - Three mile island. PMID- 17730504 TI - Three mile island. PMID- 17730506 TI - Science and public understanding. PMID- 17730507 TI - One Mars year: viking lander imaging observations. AB - Throughout the complete Mars year during which they have been on the planet, the imaging systems aboard the two Viking landers have documented a variety of surface changes. Surface condensates, consisting of both solid H(2)O and CO(2), formed at the Viking 2 lander site during the winter. Additional observations suggest that surface erosion rates due to dust redistribution may be substantially less than those predicted on the basis of pre-Viking observations. The Viking 1 lander will continue to acquire and transmit a predetermined sequence of imaging and meteorology data as long as it is operative. PMID- 17730508 TI - Science and industry, challenges of antagonistic interdependence. AB - No one is responsible for the disenchantment of American science with its customers, government and industry, and of the customers with science. But the estrangement that has replaced the earlier relationship of mutual respect, while dangerous to both sides, is a mortal threat to American science. PMID- 17730509 TI - Coral reefs in potential conflict with oil and gas development. PMID- 17730510 TI - U.s. Geological survey--on the map for 100 years. PMID- 17730511 TI - Different route accepted as way to new department. PMID- 17730512 TI - Japan-u.s. Cooperation on energy R & d agreed to. PMID- 17730513 TI - Endangered review body seems to be in the clear. PMID- 17730514 TI - On the way to the forum. PMID- 17730516 TI - Nonnonprofit chronicle of higher education. PMID- 17730515 TI - More help for the mentally ill. PMID- 17730518 TI - New breed of telescope born in Arizona. PMID- 17730517 TI - "An environmental time bomb gone off". PMID- 17730519 TI - Nonbiological limnology. PMID- 17730521 TI - Marine ecology. PMID- 17730520 TI - Weak interactions. PMID- 17730522 TI - A theory of consciousness. PMID- 17730523 TI - Geothermal convection through oceanic crust and sediments in the Indian ocean. AB - Closely spaced heat flow surveys at four sites on the flanks of the Central Indian Ridge and the Southeast Indian Ridge delineate a pattern of oscillatory heat flow which can only result from cellular convection of oceanic bottom water through the oceanic crust and overlying sediment. These cells have a wavelength of 5 to 10 kilometers and are presently active in sea floor 18 x 10(6), 25 x 10(6), and 45 x 10(6) years old of the Crozet Basin and in sea floor 55 x 10(6) years old of the Madagascar Basin. The precise measurement of nonlinear temperature profiles makes it possible to calculate the conductive and convective heat transfer components through the sea floor. Even in the oldest sites, geothermal convection is still a major component of heat transfer through both the crust and sedimentary layers. These observations coupled with the results of earlier oceanwide geothermal studies indicate that more than one-third of the entire surface area of the world's ocean floor contains presently active geothermal convection that is cellular in plan form. PMID- 17730524 TI - Stratospheric wave spectra resembling turbulence. AB - Pollution effects on ozone raise the question of the significance of turbulence in vertical transport in the stratosphere. The aircraft in situ measurements of velocity fluctuations previously employed to estimate turbulence transport were, it is hypothesized, due to atmospheric waves, despite their classical turbulence spectrum. This new hypothesis implies that previous turbulence estimates are invalid. Experimental tests are suggested. PMID- 17730525 TI - Effects of raw materials on biface manufacture. AB - It has been suggested that the degree of refinement of trimming seen on Lower Paleolithic bifaces reflects the level of technical sophistication of the toolmaker. This has been tested by a series of experiments carried out at Olduvai Gorge, Tanzania, and related to some of the archeological assemblages there. It is concluded that advanced ideas and increased mastery over raw materials do not necessarily result in stone tools that are more refined in appearance. PMID- 17730526 TI - Direct marine-continental correlation: 150,000-year oxygen isotope--pollen record from the north pacific. AB - Core Y72 II I (43 degrees 15'N, 126 degrees 22'W) contains sediment of oxygen isotope stages I through 6 (substages 5a through 5e are well developed) and abundant pollen from the nearby continent, enabling us for the first time to obtain a direct marine-continental correlation of events in the last interglacial sensu lato. From stage 6 to substage 5e the vegetational record resembles that during the waning of the last glacial. During substage 5e, after a rapid increase of alder, western hemlock was abundant and significant amounts of redwood, oak, and Douglas fir appeared. These results suggest that vegetation on the adjacent continent during substage 5e was similar to that of the temperate conifer forests which developed in the Pacific Northwest during the Holocene. The vegetation record since that brief episode (which like the Eemian in northwest Europe lasted only afew thousand years) has been complex. PMID- 17730527 TI - Power-Line Harmonic Radiation: Can It Significantly Affect the Earth's Radiation Belts? AB - It has been suggested that harmonic radiation from the earth's 50- and 60-hertz power transmission lines might significantly influence the distribution of electrons in the radiation belts. On the basis of observations presented here, it seems advisable to accept such a hypothesis with caution. New evidence suggests that power-line radiation does not play any major role in the nonadiabatic dynamics of radiation belt electrons. PMID- 17730528 TI - CARNA 5, the Small Cucumber Mosaic Virus--Dependent Replicating RNA, Regulates Disease Expression. AB - CARNA 5, the small cucummber mosaic virus-dependent replicating RNA which is the causal agent of lethal tomato necrosis disease, causes a drastic reduction of disease symptoms in at least two other plant species. Satellite-like RNA's associated with plant viruses have a disease-regulating function. PMID- 17730529 TI - Mortality of the Monarch Butterfly (Danaus plexippus L.): Avian Predation at Five Overwintering Sites in Mexico. AB - Analyses of predated butterflies on the forest floor at five monarch overwintering sites in Mexico and observations of birds foraging in mixed flocks indicate that individual birds of several species have learned to penetrate the monarch's cardenolide-based chemical defense. Predation is inversely proportional to colony size and appears to be one evolutionary explanation of the dense aggregations. PMID- 17730530 TI - "Transfer connections": specialized pathways for nutrient translocation in a red alga? AB - "Transfer connections" are morphologically and developmentally distinct pit connections in Polysiphonia (Ceramiales). They are intracellular rather than extracellular and have been observed between all cells of the diploid carposporophyte plus those specialized cells of the gametophyte suspected of providing nutritive materials to it. PMID- 17730531 TI - Products and materials. PMID- 17730532 TI - Aptitude and Achievement: Differences at the Top. PMID- 17730533 TI - Radiation Exposure Records of Personnel. PMID- 17730535 TI - Webs. PMID- 17730534 TI - Legacy of the Flexner Report. PMID- 17730536 TI - After the Manned Lunar Landing? PMID- 17730537 TI - Geophysical Observation from Nimbus I. PMID- 17730539 TI - Tomonaga, Schwinger, and Feynman Awarded Nobel Prize for Physics. PMID- 17730538 TI - Robert Burns Woodward, Nobel Prize in Chemistry for 1965. PMID- 17730540 TI - Speaker Ban (I): North Carolina Law Stirs Unrest at University. PMID- 17730541 TI - Soudan Formation: Organic Extracts of Early Precambrian Rocks. AB - Biological-type alkanes are present in rocks of the Soudan formation that are more than 2.7 x 10(9) years old, but evidence of life in Soudan times is marginal. The distributional patterns of the alkanes from various regions in the Soudan indicate an indigenous origin of these compounds. Isotopic analyses do not confirm the compositional analyses. PMID- 17730542 TI - Igneous Rocks of the Indian Ocean Floor. AB - Four dredge hauls from near the crest and from the eastern flank of the seismically active Mid-Indian Ocean Ridge at 23 degrees to 24 degrees S, at depths of 3700 to 4300 meters, produced only low-potassium tholeiitic basalt similar in chemical and mineralogic composition to basalts characteristic of ridges and rises in the Atlantic and Pacific oceans. A fifth haul, from a depth of 4000 meters on the lower flank of a seamount on the ocean side of the Indonesian Trench, recovered tholeiitic basalt with higher concentrations of K and Ti and slightly lower amounts of Si and Ca than the typical-oceanic tholeiite of the ridge. The last sample is vesicular, suggesting depression of the area since the basalt was emplaced. Many of the rocks dredged are variously decomposed and hydrated, but there is no evidence of important chemical modification toward conversion of the lava flows to spilite during extrusion or solidification. PMID- 17730543 TI - Evolution. PMID- 17730544 TI - Insect Biochemistry. PMID- 17730545 TI - Electron-Spin-Resonance, Signals and Biological Effects. PMID- 17730547 TI - THE STORY OF ISOTOPES. PMID- 17730546 TI - Forthcoming Events. PMID- 17730548 TI - THE CONGRESS AND RUSSIAN PHYSIOLOGY. PMID- 17730549 TI - PROCEEDINGS OF THE CONGRESS. PMID- 17730550 TI - DEFINITIONS OF MATHEMATICAL TERMS IN GENERAL ENGLISH DICTIONARIES. PMID- 17730551 TI - THE EFFECTS OF ZINC SALTS ON THE OXIDATION PROCESS IN PLANT CELLS. PMID- 17730553 TI - GRAVEL CUSPS ON THE CALIFORNIA COAST RELATED TO TIDES. PMID- 17730552 TI - PLIOCENE ANTELOPES OF THE PRONGHORN TYPE. PMID- 17730554 TI - CONCERNING REASONING. PMID- 17730555 TI - DEHYDRATION AND INFILTRATION. PMID- 17730556 TI - THE USE OF THE PHOTOELECTRIC CELL IN PHYSIOLOGICAL EXPERIMENTS. PMID- 17730557 TI - IMMUNOLOGICAL REACTIONS AND VISCOSITY. PMID- 17730558 TI - A MODIFIED CULTURE JAR. PMID- 17730559 TI - SODIUM AMYTAL FOR ANESTHESIA IN STUDIES ON MITOCHONDRIA. PMID- 17730560 TI - This week in science. PMID- 17730562 TI - Budget advice from the academy. PMID- 17730561 TI - Federal policies in transition. PMID- 17730564 TI - Test ban talks reach impasse. PMID- 17730563 TI - Locusts in Africa: A Plague Is Possible: Control efforts helped stave off crop destruction but better weather, armed conflict favor the insects. PMID- 17730565 TI - U.s.-Soviet ecology agreement. PMID- 17730567 TI - American Indian Language Dispute: Using a methodology not generally favored among linguists, a Stanford researcher has provoked outrage by proposing a revolutionary classification of American Indian languages. PMID- 17730566 TI - Britain Decides to Stay in CERN. PMID- 17730568 TI - PCs Factor a "Most Wanted" Number: Mathematicians at University of Georgia mobilize phalanx of personal computers to factor a 95-digit number. PMID- 17730569 TI - Souping up the Sieve. PMID- 17730570 TI - Costa rican biodiversity. PMID- 17730571 TI - Sally may ride. PMID- 17730572 TI - The energy index. PMID- 17730573 TI - California, here they go. PMID- 17730574 TI - Origins of the 1988 north american drought. AB - The 1988 summer drought in the United States was the most extensive in many years. Because the drought developed in different places at different times, not all regional effects can be traced to the same cause. Along the West Coast and in the northwestern United States drought conditions developed during 1987 in association with the 1986 to 1987 El Nino in the tropical Pacific Ocean. Record low rainfalls from April to June 1988 led to rapid development of drought in the North Central United States. Strong anticyclonic conditions and a northward displaced jet stream in the upper atmosphere over North America throughout this period were only part of pronounced and distinctive wavetrain of anomalies in the atmospheric circulation that appeared to emanate from the tropical Pacific. Below average sea surface temperatures along the equator in the Pacific in the northern spring of 1988, combined with warmer than normal water from 10 degrees to 20 degrees N, led to a northward displaced but still active intertropical convergence zone (ITCZ) southeast of Hawaii. Results from a steady-state planetarywave atmospheric model indicate that the atmospheric heating anomalies associated with the displaced ITCZ can force an anomalous wavetrain across North America similar to that observed. Land surface processes probably contributed to the severity and persistence of the drought; however, the large-scale atmospheric circulation perturbations associated with natural variations in the coupled atmosphere-ocean system in the tropical Pacific were most likely the primary cause. PMID- 17730575 TI - Laser femtochemistry. AB - Femtochemistry is concerned with the very act of the molecular motion that brings about chemistry, chemical bond breaking, or bond formation on the femtosecond (10(-15) second) time scale. With lasers it is now possible to record snapshots of chemical reactions with sub-angstrom resolution. This strobing of the transition-state region between reagents and products provides real time observations that are fundamental to understanding the dynamics of the chemical bond. PMID- 17730576 TI - Raoult's Law and the Melting Point Depression in Mesoscopic Systems. AB - Data on the melting point depression in small indium or gold particles and in liquid water held between lipid bilayers indicate that these systems obey Raoult's law, with the surface atoms or molecules acting like solute particles in a dilute solution. PMID- 17730577 TI - The Origin of the Superstructure in Bi2Sr2CaCu2O8+dgr as Revealed by Scanning Tunneling Microscopy. AB - Real-space images with atomic resolution of the BiO plane of Bi(2)Sr(2)CaCu(2)O(8+delta) were obtained with a scanning tunneling microscope. Single-crystal samples were cleaved and imaged under ultrahigh vacuum conditions at room temperature. The images clearly show the one-dimensional incommensurate superstructure along the b-axis that is common to this phase. High-resolution images show the position of the Bi atoms, revealing the structural nature of the superlattice. A missing row of Bi atoms occurs either every nine or ten atomic sites in both (110) directions, accounting for the measured incommensurate periodicity of the superstructure. A model is proposed that includes missing rows of atoms, as well as displacements of the atomic positions along both the a- and c-axis directions. PMID- 17730578 TI - Gravitational separation of gases and isotopes in polar ice caps. AB - Atmospheric gases trapped in polar ice at the firn to ice transition layer are enriched in heavy isotopes (nitrogen-15 and oxygen-18) and in heavy gases (O(2)/N(2) and Ar/N(2) ratios) relative to the free atmosphere. The maximum enrichments observed follow patterns predicted for gravitational equilibrium at the base of the firn layer, as calculated from the depth to the transition layer and the temperature in the firn. Gas ratios exhibit both positive and negative enrichments relative to air: the negative enrichments of heavy gases are consistent with observed artifacts of vacuum stripping of gases from fractured ice and with the relative values of molecular diameters that govern capillary transport. These two models for isotopic and elemental fractionation provide a basis for understanding the initial enrichments of carbon-13 and oxygen-18 in trapped CO(2), CH(4), and O(2) in ice cores, which must be known in order to decipher ancient atmospheric isotopic ratios. PMID- 17730579 TI - The Non-Darwinian Revolution. Reinterpreting a Historical Myth. Peter . Bowler. Johns Hopkins University Press, Baltimore, 1988. xii, 238 pp., illus. $27.50. PMID- 17730580 TI - Thinking About Science. Max Delbruck and the Origins of Molecular Biology. Ernst Peter Fischer and Carol Lipson. Norton, New York, 1988. 334 pp., illus. $19.95. PMID- 17730583 TI - Products & materials. PMID- 17730582 TI - The Lightning Discharge. Martin A. Uman. Academic Press, San Diego, CA, 1987. xii, 377 pp., illus. $49. International Geophysics Series, vol. 39. PMID- 17730581 TI - Transposition. A. J. Kingsman, K. F. Chater, and S. M. Kingsman, Eds. Published for the Society for General Microbiology by Cambridge University Press, New York, 1988. xvi, 375 pp., illus. $75. Symposia of the Society for General Microbiology, vol. 43. From a symposium, Coventry, U.K., April 1988. PMID- 17730584 TI - COMMENT AND CRITICISM. PMID- 17730585 TI - THE ALERT EXPEDITION. PMID- 17730586 TI - THE RECENT EDUCATIONAL MEETING IN BOSTON. PMID- 17730587 TI - USE AND ABUSE OF LEARNED SOCIETIES. PMID- 17730588 TI - THE FLOOD ROCK EXPLOSION FELT AT HARVARD COLLEGE. PMID- 17730589 TI - AN ADVANCE IN FISH CULTURE. PMID- 17730590 TI - SOCIAL PHILOSOPHY AND RELIGION OF COMTE. PMID- 17730591 TI - RUSSIA UNDER THE TZARS. PMID- 17730592 TI - GEOGRAPHICAL NOTES. PMID- 17730593 TI - JOHNSON'S SURVEYING. PMID- 17730594 TI - ASTRONOMICAL NOTES. PMID- 17730595 TI - WASHINGTON LETTER. PMID- 17730597 TI - An attempt to photograph the corona. PMID- 17730598 TI - Voss-Holtz electrical machine. PMID- 17730596 TI - LETTERS TO THE EDITOR. PMID- 17730600 TI - Pressure on basic research. PMID- 17730599 TI - Nsf. PMID- 17730601 TI - Dynamic programming. AB - Little has been done in the study of these intriguing questions, and I do not wish to give the impression that any extensive set of ideas exists that could be called a "theory." What is quite surprising, as far as the histories of science and philosophy are concerned, is that the major impetus for the fantastic growth of interest in brain processes, both psychological and physiological, has come from a device, a machine, the digital computer. In dealing with a human being and a human society, we enjoy the luxury of being irrational, illogical, inconsistent, and incomplete, and yet of coping. In operating a computer, we must meet the rigorous requirements for detailed instructions and absolute precision. If we understood the ability of the human mind to make effective decisions when confronted by complexity, uncertainty, and irrationality then we could use computers a million times more effectively than we do. Recognition of this fact has been a motivation for the spurt of research in the field of neurophysiology. The more we study the information processing aspects of the mind, the more perplexed and impressed we become. It will be a very long time before we understand these processes sufficiently to reproduce them. In any case, the mathematician sees hundreds and thousands of formidable new problems in dozens of blossoming areas, puzzles galore, and challenges to his heart's content. He may never resolve some of these, but he will never be bored. What more can he ask? PMID- 17730603 TI - Wilderness act: great smoky plan debated. PMID- 17730602 TI - Mohole: senate is asked to restore funds. PMID- 17730604 TI - Franco-Russian Collaboration in Science: De Gaulle's Visit. PMID- 17730605 TI - What the French president saw: a gallic view of novosibirsk. PMID- 17730606 TI - Pygmy stars: first pair. AB - The binary LP 101-15/16 having the proper motion of 1.62 seconds of arc per year has been studied with the prime-focus spectrograph of the 200-inch (508 cm) telescope. Indications are that LP 101-15/16 is the first pair of pygmy stars ever discovered. One of its components, LP 101-16, is probably a blue pygmy star which is at least four magnitudes fainter than the ordinary white dwarfs. Also, two of the Balmer lines in absorption appear to be displaced toward the red by amounts which indicate the existence of an Einstein gravitational red shift corresponding to about 1000 km sec-1. On the other hand LP 101-15 is red and shows an entirely new type of spectrum, which suggests that it may be a first representative of a type of red pygmy star which is 2.5 magnitudes fainter than the M-type dwarf stars of the main sequence. PMID- 17730607 TI - Chondrules: suggestion concerning the origin. AB - The millimeter-sized, sometimes glassy spheroids called chondrules that occur abundantly in stony meteorites may have been produced by lightning in the primitive Laplaciantype nebula while earthy materials were condensing and collecting to form the asteroids and the terrestrial planets. PMID- 17730608 TI - Martian wave of darkening: a frost phenomenon? AB - A new hypothesis attributes the Martian "wave of darkening" to soil frost phenomena. Diurnal thawing and freezing of the ground, which uses moisture transported by the atmosphere from the melting polar cap, can produce various minute, frost-heaved, soil surface features. These microrelief features result in a complex porous surface structure, which causes optical darkening. The boundary at which the wave of darkening terminates on the winter hemisphere correlates with the latitude at which the diurnal peak surface temperature drops below 0 degrees C. The hypothesis is examined in terms of known properties of the Martian atmosphere and surface and the availability of water. PMID- 17730609 TI - Cohenite in meteorites: a proposed origin. AB - Cohenite [(Fe, Ni)(3)C] is found almost exclusively in meteorites containing from 6 to 8 percent nickel (by weight). On the basis of iron-nickel-carbon phase diagrams at 1 atmosphere and of kinetic data, the occurrence of cohenite within this narrow composition range as a low-pressure metastable phase and the nonoccurrence of cohenite in meteorites outside the range 6 to 8 percent nickel can be explained. Cohenite formed in meteorites containing less than 6 to 8 percent nickel decomposed to metal and graphite during cooling; it cannot form in meteorites containing more than about 8 percent. The presence of cohenite in meteorites cannot be used as an indicator of pressure of formation. However, the absence of cohenite in meteorites containing the assemblage, metal plus graphite, requires low pressures during cooling. PMID- 17730610 TI - Copper and the role of isopods in degradation of organic matter. AB - On an artificial substrate of filter paper, Porcellio scaber cannot extract copper from leaf litter. If one increases the copper content of the food by soaking the leaves in solutions of CuSO(4) or in organic extracts, assimilation of copper becomes possible, but only at concentrations higher than 1 microgram of copper per milligram of ash. This is too high a level for primary vegetable matter to be considered a plausible source of copper for isopods. I present evidence that in fecal material the critical level at which assimilation of copper becomes feasible is lower than in primary organic material by nearly an order of magnitude, and that isopods are obliged to switch to coprophagy in order to allow accumulation of copper in their bodies. PMID- 17730611 TI - Nitrogen- and helium-induced anoxia: different lethal effects on rye seeds. AB - Prolonged exposures to acute anoxia caused progressive reductions in the viability of hydrated seeds of Prolific rye. For equal exposures of 9 days or longer, mortality was significantly higher in helium than in nitrogen. The findings suggest that prolonged use of helium as a component of atmospheres in manned space capsules may be harmful. PMID- 17730613 TI - Calibration of Beta gauges for determining leaf water status. AB - The recent development of beta gauges for the indirect determination of the water status of plants has had a widespread impact on plant ecological-physiological research. Calibration of these instruments has, however, been tedious and cumbersome, involving repeated simultaneous measurements of beta absorption and leaf water content. This procedure can be much simplified, as long as the beta absorption at a single known relative water content is measured, together with the turgid and dry weights of a sample of leaf discs. PMID- 17730612 TI - Montmorillonite: Effect of pH on Its Adsorption of a Soil Humic Compound. AB - The d(001) spacing of sodium montmorillonite increased from 9.87 to 17.50 angstroms after interaction of the compound with fulvic acid at pH 2.5. The magnitude of the spacing decreased with increase in pH between 2.5 and 6.0. A t pH 2.5 40 milligrams of Namontmorillonite adsorbed 31 mg of fulvic acid; at pH 6.0, only 15.8 mg. PMID- 17730614 TI - Higher education: a population flow feedback model. PMID- 17730616 TI - Forthcoming events. PMID- 17730615 TI - Nucleic Acid and protein chemistry. PMID- 17730618 TI - HUGH HAMPTON YOUNG 1870-1945. PMID- 17730617 TI - SCIENTIFIC RESEARCH BILLS BEFORE THE UNITED STATES SENATE. PMID- 17730619 TI - IN HONOR OF DR. ERNST A. BESSEY. PMID- 17730620 TI - AWARDS OF THE AMERICAN INSTITUTE OF NUTRITION. PMID- 17730621 TI - NEWS FROM ABROAD. PMID- 17730622 TI - THE ACTION OF HORSERADISH-PEROXIDASE ON ANGIOTONIN, PEPSITENSIN AND EPINEPHRINE. AB - (1) The pressor action of angiotonin, pepsitensin and epinephrine is rapidly destroyed by the horseradish-peroxidase-hydrogen peroxide system. (2) This reaction is considerably enhanced by the addition of small amounts of potassium iodide. PMID- 17730623 TI - THE RELATIONSHIP OF THE AGENT OF HEART-WATER FEVER--RICKETTSIA RUMINANTIUM. AB - Sera from sheep which were infected with heartwater fever from 39 to 110 days before the serum was withdrawn failed to fix complement in the presence of lymphogranuloma venereum antigen. PMID- 17730624 TI - ON THE ORIGIN AND FATE OF THE FATTY INCLUSIONS IN A STRAIN OF BACILLUS CEREUS. PMID- 17730625 TI - THE COMPARATIVE ANTIFOULING EFFICACY OF DDT. PMID- 17730626 TI - THE EFFECT OF PENICILLIN ON THE LETHAL ACTION OF MENINGOCOCCAL ENDOTOXIN IN EXPERIMENTAL ANIMALS. PMID- 17730627 TI - PHYSIOLOGICAL COMPARISON OF TWO STRAINS OF PENICILLIUM. PMID- 17730628 TI - SCIENTIFIC APPARATUS AND LABORATORY METHODS THE HISTOCHEMICAL LOCALIZATION OF ADENOSINETRIPHOSPHATASE IN PLANT AND ANIMAL TISSUES. AB - A method has been described for the histochemical localization of acid and alkaline ATPase in plant and animal tissues respectively. A hanging-drop technique has been developed that permits the use of a minimum of substrate, i.e., one small drop for each tissue section. ATPase in wheat was demonstrated for the first time. PMID- 17730629 TI - THE EFFECT OF MOTION PICTURES ON BODY TEMPERATURE. PMID- 17730630 TI - SCIENCE IN RUSSIA. PMID- 17730631 TI - "THIS IS THE ENEMY". PMID- 17730632 TI - Mosher's Expulsion from Stanford. PMID- 17730633 TI - Mosher's Expulsion from Stanford. PMID- 17730634 TI - The rotation of spiral galaxies. AB - There is accumulating evidence that as much as 90 percent of the mass of the universe is nonluminous and is clumped, halo-like, around individual galaxies. The gravitational force of this dark matter is presumed to be responsible for the high rotational velocities of stars and gas in the disks of spiral galaxie. At present, the form of the dark matter is unknown. Possible candidates span a range in mass of 10(70), from non-zero-mass neutrinos to massive black holes. PMID- 17730635 TI - Inelastic electron tunneling spectroscopy. AB - Inelastic electron tunneling spectroscopy is a useful technique for the study of vibrational modes of molecules adsorbed on the surface of oxide layers in a metal insulator-metal tunnel junction. The technique involves studying the effects of adsorbed molecules on the tunneling spectrum of such junctions. The data give useful information about the structure, bonding, and orientation of adsorbed molecules. One of the major advantages of inelastic electron tunneling spectroscopy is its sensitivity. It is capable of detecting on the order of 10(10) molecules (a fraction of a monolayer) on a 1-square-millimeter junction. It has been successfully used in studies of catalysis, biology, trace impurity detection, and electronic excitations. Because of its high sensitivity, this technique shows great promise in the area of solid-state electronic chemical sensing. PMID- 17730636 TI - Bugs in the yellow rain theory. PMID- 17730637 TI - Lobbying pays off for catholic u. And columbia. PMID- 17730638 TI - Xerox Scientist Joins DOD Supercomputer Program. PMID- 17730639 TI - Acid rain researchers issue joint report. PMID- 17730641 TI - NSF, Do You Take NBS . . . ? PMID- 17730640 TI - High-tech soviet problems. PMID- 17730642 TI - Trace gases could double climate warming. PMID- 17730643 TI - The infrared astronomy satellite (I). PMID- 17730644 TI - Using time to measure length. PMID- 17730646 TI - An intellectual migration. PMID- 17730645 TI - Isotopes give clues to past diets. PMID- 17730647 TI - Anoxic strata. PMID- 17730649 TI - Yeast molecular biology. PMID- 17730648 TI - Embryonic development. PMID- 17730650 TI - Titan: discovery of carbon monoxide in its atmosphere. AB - The 3-0 rotation-vibration band of carbon monoxide in the near-infrared spectrum of Titan has been identified, and a reflecting layer model mixing ratio of carbon monoxide to molecular nitrogen of 6 x 10(-5) has been determined. This result supports the probable detection of carbon dioxide by Samuelson and his co-workers and strengthens possible analogies between the atmosphere of Titan and conditions on primitive Earth. PMID- 17730651 TI - Reversible loss of gravitropic sensitivity in maize roots after tip application of calcium chelators. AB - The application of calcium chelating agents (EDTA or EGTA) to the tips of maize roots caused a loss of gravitropic sensitivity. When the chelator was replaced with calcium chloride, gravitropic sensitivity was restored. Asymmetric application of calcium chloride near the tip of a vertical root caused curvature toward the calcium source. When the calcium was applied to the upper surface of the tip of a root oriented horizontally, the root curved upward even though control roots exhibited strong downward curvature. Application of calcium chloride to the tips of decapped roots, which are known to be gravitropically insensitive, did not restore gravitropic sensitivity. However, asymmetric application of calcium chloride near the tips of decapped roots caused curvature toward the calcium source. Calcium may play a key role in linking gravity detection to gravitropic curvature in roots. PMID- 17730652 TI - Sighting of el chichon sulfur dioxide clouds with the nimbus 7 total ozone mapping spectrometer. AB - The eruptions of El Chichon volcano on 28 March and 3 and 4 April 1982 were observed by the Nimbus 7 total ozone mapping spectrometer due to strong absorption by volcanic gases at the shortest wavelengths of the spectrometer (312.5 and 317.5 nanometers). These ultraviolet pictures permit a measurement of the volume, dispersion, and drift of volcanic gas clouds. The tropospheric clouds were rapidly dispersed in westerly winds while persistent stratospheric clouds drifted in easterly winds at speeds up to 13 meters per second. The spectral reflectance is consistent with sulfur dioxide absorption and rules out carbon disulfide as a major constituent. A preliminary estimate of the mass of sulfur dioxide deposited in the stratosphere by the large eruptions on 3 and 4 April is 3.3 x 10(6) tons. Prior estimates of volcanic cloud volume were based on extrapolation of locally measured sulfur dioxide concentrations. PMID- 17730654 TI - Cell polarity: endogenous ion currents precede and predict branching in the water mold achyla. AB - The hyphae of the water mold Achyla bisexualis generate electrical currents that enter the growing tips and leave farther back. An inward-moving current also precedes branching and predicts the site of branch emergence; during the branching process, the current at the original tip declines or even reverses transiently without any change in growth rate. The inward current probably acts as an early signal during branch differentiation. The flow of specific ions rather than the flow of electrical charge probably serves to localize growth. PMID- 17730653 TI - Venus: global surface radio emissivity. AB - Observations of thermal radio emission from the surface of Venus, made by the Pioneer Venus radar mapper at a wavelength of 17 centimeters, show variations that are dominated by changes in surface emissivity. The regions of lowest emissivity (0.54 +/- 0.05 for the highland areas of Aphrodite Terra and Theia Mons) correspond closely to regions of high radar reflectivity reported earlier. These results support the inference of inclusions of material with high electrical conductivity in the surface rock of these areas. PMID- 17730655 TI - Sex Pheromone Biosynthesis in Trichoplusia ni: Key Steps Involve Delta-11 Desaturation and Chain-Shortening. AB - In addition to the primary pheromone component (Z)-7-dodecenyl acetate, the sex pheromone gland of Trichoplusia ni contains the immediate fatty acyl precursor (Z)-7-dodecenoate and a large quantity of (Z)-11-hexadecenoate. Labeling experiments showed that (Z)-11-hexadecenoate is chain-shortened to (Z)-9 tetradecenoate, and that this in turn is chain-shortened to (Z)-7-dodecenoate. The same mechanism appears to explain the sex pheromone compositions of many other moth species. PMID- 17730656 TI - Sucrose: a constitutive elicitor of phytoalexin synthesis. AB - Extracts of seeds and leaves of the tropical legume Cajanus cajan (L.) Millsp. (the pigeon pea) elicited the accumulation of three phytoalexins when applied as droplets to superficially wounded leaves of the plant. The active component was purified and identified as sucrose. Phytoalexin accumulation was proportional to the logarithm of the concentration of sucrose applied, with maxima ranging from 338 to 455 micrograms per gram (fresh weight) of leaf tissue. The sucrose concentrations required to elicit half these amounts ranged from 20 to 35 micrograms per milliliter, but other sugars had little effect even at 1000 micrograms per milliliter. The elicitor activity of sucrose was abolished by actinomycin D, puromycin, and cycloheximide at a concentration of 10 micrograms per milliliter or greater, suggesting that gene derepression is required for expression of the phytoalexin response. PMID- 17730657 TI - Ecology and catastrophic mortality in wild horses: implications for interpreting fossil assemblages. AB - The identities, sexes, and reproductive status of groups of wild horses (Equus caballus) living in the Great Basin Desert of North America were known prior to their deaths on ridgelines. Another group of very young horses died on a quagmire. Snow accumulation or drought was apparently responsible for the mass deaths. These data have implications for reconstructing some aspects of the social structure of fossil mammals on the basis of skewed sex or age ratios in bone assemblages. PMID- 17730658 TI - Reverse diel vertical migration: an escape from invertebrate predators. AB - The marine copepod Pseudocalanus sp. exhibits an unusual reverse diel vertical migration in Dabob Bay, Washington, concurrently with a normal vertical migration by nocturnal invertebrate predators. Reduced spatial overlap with predators appears to decrease mortality rate of adult female Pseudocalanus. A life table analysis suggests that the demographic disadvantage associated with daily migration across a thermal gradient can be overcome if mortality is reduced by as little as 16 percent. PMID- 17730659 TI - Morphological correlates of differences in pheromone sensitivity in insect sensilla. AB - Scanning electron microscopy and single unit recordings of male Trichoplusia ni antennae reveal at least two classes of pheromone-sensitive sensilla trichodea. The longer sensillum contains two receptor neurons each with small amounts of spontaneous activity. One neuron responds to large (10-microgram) doses of (Z)-7 dodecenyl acetate, a component of the female sex pheromone. The shorter sensillum contains two receptor neurons both with larger amounts of spontaneous activity and increased sensitivity to low (0.01-microgram) doses of pheromone. PMID- 17730660 TI - Sea spray production from bubbles. PMID- 17730662 TI - When Boys Will be Buys. PMID- 17730661 TI - Sea spray production from bubbles. PMID- 17730663 TI - Desert Geomorphology in the Arabian Peninsula. PMID- 17730664 TI - The New Administration: It Faces a Number of Questions of Scientific Policy; No Easy Solutions in Sight. PMID- 17730665 TI - Libby and Glaser Win Nobel Awards in Chemistry and Physics. PMID- 17730666 TI - Discovery of Eocene Sediments in Subsurface of Cape Cod. AB - Spores, pollen, and charcoal taken from two wells drilled near the tip of Cape Cod have been identified as Eocene. These are the first Eocene rocks to be identified in Massachusetts. Interpretation of seismic records taken in the Gulf of Maine and Cape Cod Bay will be influenced by this discovery. PMID- 17730667 TI - Venation Polymorphism and Genetic Variability in Drosophila melanogaster Loew. AB - Experimental evidence indicates that phenocopy production may provide an inflated estimate of the importance of genetic variability and recombination in the production of venation phenodeviants. PMID- 17730668 TI - Callus Tissues from the Mosses Polytrichum and Atrichum. AB - Callus-like tissues, isolated from protonemal cultures of two species of mosses, grow vigorously and without marked differentiation on media containing sucrose, casamino acids, and coconut milk. On mineral agar and on media containing sorbitol the tissue from Polytrichum (found diploid) reverts to the growth pattern of apparently normal moss plants. PMID- 17730669 TI - Programs Planned for the AAAS New York Meeting. PMID- 17730670 TI - Biological Organization. PMID- 17730671 TI - Letters to the Editor. PMID- 17730672 TI - Letters to the Editor. PMID- 17730673 TI - Dream Deprivation. PMID- 17730674 TI - Letters to the Editor. PMID- 17730675 TI - Letters to the Editor. PMID- 17730676 TI - Craftsmen and Physicists. PMID- 17730677 TI - Letters to the Editor. PMID- 17730679 TI - Forthcoming Events. PMID- 17730678 TI - Friends of the Pleistocene. PMID- 17730680 TI - INTRODUCTORY REMARKS AND COMMENTS. PMID- 17730681 TI - ADDRESS OF THE HONORABLE ANDREW W. MELLON. PMID- 17730682 TI - ADDRESS OF RICHARD K. MELLON. PMID- 17730684 TI - THE NEEDS OF THE MIMICRY THEORY. PMID- 17730683 TI - ROBERT KENNEDY DUNCAN. PMID- 17730685 TI - AN ANALOGUE OF PLATEAU'S SPHERULE. PMID- 17730687 TI - MINUTES OF THE EXECUTIVE COMMITTEE. PMID- 17730688 TI - SEASIDE SHRUBS: WIND FORMS VS. SPRAY FORMS. PMID- 17730686 TI - HETEROTHALLISM IN VENTURIA INAEQUALIS. PMID- 17730689 TI - ACTIVITIES OF MELLON INSTITUTE DURING THE PAST YEAR. PMID- 17730690 TI - PIMELIC ACID AS A GROWTH ACCESSORY FACTOR FOR A STRAIN OF THE DIPHTHERIA BACILLUS. PMID- 17730691 TI - BIOLOGICAL ASSAYS FOR FLAVIN AND DERMATITIS FACTOR(S). PMID- 17730693 TI - The Process Known as Scapegoating. PMID- 17730692 TI - THE DISTRIBUTION OF GENE FREQUENCIES IN POPULATIONS. PMID- 17730694 TI - Meetings & Conferences. PMID- 17730695 TI - Science and Human Nature. PMID- 17730696 TI - An Explanation of the Lake Michigan Wave of 26 June 1954. PMID- 17730697 TI - Saul Dushman, Unofficial "Dean of Men" of the General Electric Research Laboratory. PMID- 17730698 TI - Miscellaneous Publications. PMID- 17730699 TI - Use of Factors for Converting Carbon or Nitrogen to Total Sedimentary Organics. PMID- 17730700 TI - Source of Error in Determination of Chromic Oxide Using Perchloric-Sulfuric Acid Digestion Method. PMID- 17730701 TI - Chemical Induction of Flowering in the Sweetpotato. PMID- 17730702 TI - Genetics of Homothallic Fungi. PMID- 17730703 TI - Detection of M-Regions in Geomagnetic Data. PMID- 17730704 TI - Visual Receptor Lamellation and Active Rhodopsin. PMID- 17730706 TI - PELLAGRA-PREVENTING FOODS. PMID- 17730705 TI - Water-Soluble Chelates in Histochemical Staining. PMID- 17730707 TI - THE STUDY OF INFLUENZA. PMID- 17730708 TI - THE CALIFORNIA BIG TREES. PMID- 17730709 TI - THE LEVEL OF THE GREAT LAKES. PMID- 17730710 TI - THE MUSICAL ABILITY OF NEGROES. PMID- 17730711 TI - THE RELATION OF STATISTICS TO MODERN MATHEMATICAL RESEARCH. PMID- 17730712 TI - THE INCREASED EFFICIENCY OF AMERICAN AGRICULTURE. PMID- 17730713 TI - THE WORLD'S TWO GREATEST PETRIFIED FORESTS. PMID- 17730714 TI - SAMUEL BONSALL PARISH. PMID- 17730716 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17730715 TI - THE MISSING LINK IN STELLAR EVOLUTION. PMID- 17730717 TI - RESONANCE RADIOMETRY. PMID- 17730718 TI - PRICKLY PEAR WORK. PMID- 17730719 TI - DISSOCIATION OF NEUTRAL VACCINE VIRUS-IMMUNE SERUM MIXTURES. PMID- 17730720 TI - HALL EFFECT IN SINGLE METAL CRYSTAL. PMID- 17730722 TI - THE GROWTH OF HOOKWORM LARVAE ON PURE CULTURES OF BACTERIA. PMID- 17730721 TI - THE INFLUENZA EPIDEMIC. PMID- 17730723 TI - MOUNTING AMPHIBIA BY PARAFFIN INFILTRATION. PMID- 17730724 TI - THE EXCITATION OF LUMINESCENCE BY THE AGITATION OF MERCURY IN GLASS AND TRANSPARENT FUSED SILICA TUBES AND VESSELS. PMID- 17730725 TI - THE INORGANIC CONSTITUENTS OF MILK. PMID- 17730726 TI - McNamara in Mississippi. PMID- 17730727 TI - Selection of NIH Director. PMID- 17730728 TI - Grand canyon still threatened. PMID- 17730729 TI - Letter to the editor. PMID- 17730730 TI - Letter to the editor. PMID- 17730731 TI - Frustrations of eastern science. PMID- 17730732 TI - Canada's Science Council: Incomplete Representation. PMID- 17730733 TI - Prior preparation pays. PMID- 17730734 TI - Rabbits first-then humans. PMID- 17730735 TI - The Succession at NIH. PMID- 17730736 TI - Atom reactions in flow tubes. PMID- 17730738 TI - Higher education: scrambling for the philanthropic dollar. PMID- 17730739 TI - Precambrian Fossils (?) near Elliot Lake, Ontario. AB - Complex structures in Upper Huronian (Lower Proterozoic) quartzite north of Lake Huron are interpreted as probable metazoan fossils aged between 2 and 2.5 x 10(9) years. They are preserved as sand casts in the form of curved spindles having inclined lateral corrugations, axial marking, and apparent bilateral symmetry. PMID- 17730740 TI - Mossbauer analysis of iron in clay minerals. AB - Mossbauer absorption spectrography can be used to establish the presence of Fe(2)+ and Fe(3)+ in clay minerals. In the sheet structure silicates, octahedrally coordinated iron can be distinguished from tetrahedrally coordinated iron. Siderite and goethite, common contaminants of the clay minerals, can usually be detected. Goethite has a well-organized structure, though, owing to its fine grain size, it may appear to be amorphous to x-rays. The various families of clay minerals show minor differences in isomer shift and quadrupole splitting values, caused by variations in the character of the octahedral layer. PMID- 17730741 TI - Alga-like fossils from the early precambrian of South Africa. AB - Micropaleontological studies of carbonaceouis chert from the Fig Tree Series of South Africa (> 3.1 x 10(9) years old) revealed the presence of spheroidal microfossils, here designated Archaeosphaeroides barbertonensis, interpreted as probably representing the remnants of unicellular alga-like organisms. The presumed photosynthetic nature of these primitive microorganisms seems corroborated by organic geochemical and carbon isotopic studies of the Fig Tree organic matter, and is consistent with the geologically and mineralogically indicated Early Precambrian environment. These alga-like spheroids, together with a bacterium-like organism previously described from the Fig Tree chert, are the oldest fossil orgisms now known. PMID- 17730742 TI - Uranium distribution in rocks by fission-track registration in lexan plastic. AB - When Lexan plastic is iused to register fission tracks from thermal neutron induced fission of uranium in rocks, a print of the rock texture is formed on the plastic surface after chemical etching. This print allows positive, rapid location of uranium-bearing phases in the rock and accurate determination of uranium abundances. PMID- 17730743 TI - Red sea: detailed survey of hot-brine areas. AB - A bathymetric and geophysical survey of the Red Sea rift valley between 21 degrees 10' and 21 degrees 30'N has defined three separate pools of hot brines. The brines and their associated heavy metals are believed to be periodically discharged from the eastern side of the largest deep, Atlantis II. Cores taken from the flanks of the deeps show repetitive cycles of sedimentation of hydrous amorphous iron oxides which fill most of Atlantis II Deep. PMID- 17730745 TI - Selective Forces in Papilio glaucus. PMID- 17730744 TI - Glycerol excretion by symbiotic algae from corals and tridacna and its control by the host. AB - Zooxanthellae isolated from reef corals and Tridacna crocea incorporate labeled carbon dioxide photosynthetically. In the presence of some component of the host tissue, up to 40 percent of the labeled algal photosynthate is liberated primarily as glycerol. Excretion of glycerol by the algae in situ and its control and utilization by the host may represent a mechanism by which zooxanthellae contribute to produtctivity of coral reefs. PMID- 17730746 TI - National academy of sciences. PMID- 17730747 TI - SEACOAST DEFENCES. PMID- 17730748 TI - METEOROLOGY IN CALIFORNIA. PMID- 17730750 TI - CONSUMPTION IN PENNSYLVANIA. PMID- 17730749 TI - THAYER'S GREEK-ENGLISH LEXICON. PMID- 17730752 TI - COMPARATIVE MORPHOLOGY. PMID- 17730751 TI - THE WINNIPEG COUNTRY. PMID- 17730753 TI - THE LIFE OF HAMILTON. PMID- 17730754 TI - THE CARNEGIE TECHNICAL UNIVERSITY. PMID- 17730755 TI - A NATIONAL UNIVERSITY. PMID- 17730757 TI - THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17730756 TI - RADIO-ACTIVE SUBSTANCES AND THEIR RADIATIONS. PMID- 17730758 TI - CURRENT NOTES ON PHYSIOGRAPHY. PMID- 17730759 TI - BOTANICAL NOTES. PMID- 17730760 TI - CONFERRING OF DEGREES AT THE UNIVERSITY OF CHICAGO. PMID- 17730761 TI - THE AMERICAN PHILOSOPHICAL SOCIETY. PMID- 17730762 TI - JOACHIM BARRANDE. PMID- 17730763 TI - WHIRLWINDS, CYCLONES, AND TORNADOES.--IV. PMID- 17730765 TI - CRYSTALS IN THE BARK OF TREES. PMID- 17730764 TI - THE ELECTRIC LIGHT ON THE U. S. FISH-COMMISSION STEAMER ALBATROSS.--III. PMID- 17730766 TI - THE PHYSIOLOGICAL STATION OF PARIS.--II. PMID- 17730767 TI - THE FUNDAMENTAL CATALOGUE OF THE BERLINER JAHRBUCH. PMID- 17730768 TI - Analysis of the wild potato. PMID- 17730769 TI - Report of the Assos meeting. PMID- 17730770 TI - English ch. PMID- 17730771 TI - SOME RECENT STUDIES ON IDEAS OF MOTION. PMID- 17730772 TI - November shower of meteors. PMID- 17730773 TI - Musical sand. PMID- 17730774 TI - INTELLIGENCE FROM AMERICAN SCIENTIFIC STATIONS. PMID- 17730775 TI - SCIENCE NEWS. PMID- 17730776 TI - THE ORIGIN OF MAN FROM A BRACHIATING ANTHROPOID STOCK. PMID- 17730778 TI - IN HONOR OF DR. WELCH. PMID- 17730777 TI - THE WAVE PROPERTIES OF ELECTRONS. PMID- 17730779 TI - THE QUESTION OF THE CENTRAL BODIES. PMID- 17730781 TI - GENETICS. PMID- 17730780 TI - CREDIT OR RESPONSIBILITY IN SCIENTIFIC PUBLICATION. PMID- 17730782 TI - MALFORMED LEG BONES IN YOUNG CHICKENS. PMID- 17730783 TI - AN IMPROVED COLOR STANDARD FOR THE COLORIMETRIC DETERMINATION OF CHLOROPHYLL. PMID- 17730785 TI - THE BEHAVIOR OF WINTER WHEAT IN ARTIFICIAL ENVIRONMENTS. PMID- 17730784 TI - A STORAGE TUBE FOR PLASMA AND EMBRYO JUICE. PMID- 17730786 TI - VITAMIN B2. PMID- 17730787 TI - THE CYTOLOGY OF CILIA FORMATION IN THE SWARM-SPORES OF MYXOMYCETES. PMID- 17730788 TI - Innovation. PMID- 17730789 TI - Science centennial. PMID- 17730790 TI - Changes in atmospheric carbon-14 attributed to a variable sun. AB - The (14)C production rate in the upper atmosphere changes with time because the galactic cosmic-ray flux responsible for (14)C production is modulated by the changes in solar wind magnetic properties. The resulting changes in the atmospheric (14)C level are recorded in tree rings and are used to calculate past (14)C production rates from a carbon reservoir model that describes terrestrial carbon exchange between the atmosphere, ocean, and biosphere. These past (14)C production rate changes are compared with (14)C production rates determined from 20th-century neutron flux measurements, and a theory relating (14)C production and solar variability, as given by geomagnetic Aa indices and sunspot numbers, is developed. This theory takes into account long-term solar changes that were previously neglected. The 860-year (14)C record indicates three episodes when sunspots apparently were absent: A.D. 1654 to 1714 (Maunder minimum), 1416 to 1534 (Sporer minimum), and 1282 to 1342 (Wolf minimum). A less precisely defined minimum occurred near A.D. 1040. The part of this record after A.D. 1645 correlates well with the basic features of the historical record of sunspot numbers. The magnitude of the calculated (14)C production rates points to a further increase in cosmic-ray flux when sunspots are absent. This flux was greatest during the Sporer minimum. A record of approximate sunspot numbers and Aa indices for the current millennium is also presented. PMID- 17730791 TI - Working women scientists and engineers. AB - About 80 percent of women trained in science or engineering are in the labor force, but many are employed outside of their fields. Most who withdraw from the labor force do so temporarily, and about half do not take a career break even when they have small children. Factors affecting labor force participation are student status, highest degree level, parental status and age of children, and field of degree. Employment opportunities are restricted in some fields, and women have higher unemployment rates and lower earnings than men. Some policy changes would improve opportunities for women, and better data are needed to monitor their participation in science and technology. PMID- 17730792 TI - FAA Attacked over Traffic Control Technology. PMID- 17730793 TI - Appropriate technology and the too high outhouse. PMID- 17730794 TI - Agent orange again. PMID- 17730795 TI - A dearth of phosphate? PMID- 17730796 TI - Scientists favorable toward extrasensory perception. PMID- 17730797 TI - The 1979 nobel prize for chemistry. AB - The 1979 Nobel Prize for Chemistry has been awarded jointly to Georg Wittig of the University of Heidelberg and Herbert C. Brown of Purdue University for their separate work in organic synthesis. Wittig's major achievement was the development of a highly specific method for the synthesis of olefins. Brown found major new routes to add substituents to olefins selectively. Both employed elements that had found little previous use in organic synthesis, and both prospered by following up on unexpected observations. PMID- 17730798 TI - Brown: passes through the mountains (1). PMID- 17730799 TI - Lobster-Eye X-ray Telescope Envisioned. PMID- 17730800 TI - A managerial view of research. PMID- 17730801 TI - Geology in retrospect. PMID- 17730802 TI - Metallurgy in antiquity. PMID- 17730804 TI - Energy transitions. PMID- 17730803 TI - Neurophysiology. PMID- 17730805 TI - Science: a weekly record of scientific progress. PMID- 17730806 TI - AAAS Socio-Psychological Prize. PMID- 17730807 TI - Science, engineering, and diplomacy fellowships established. PMID- 17730808 TI - Record salaries for scientists and engineers battered by inflation. PMID- 17730809 TI - For the library. PMID- 17730810 TI - Toronto meeting in 1981. PMID- 17730811 TI - Youth activities in san francisco. PMID- 17730812 TI - International bio-energy conference scheduled for april. PMID- 17730813 TI - A meteoritic component rich in volatile elements: its characterization and implications. AB - An unusual carbon-rich material found in the Abee meteorite is highly enriched in volatile elements, by factors of 10(4) relative to the case for nonvolatile elements. Volatile-rich material of this type might form in the solar nebula toward the end of accretion, when small amounts of residual dust acquire all the uncondensed volatile elements. The mercury enrichment factor of 8500 could explain the paradox of the excess abundance of this element in meteorites. PMID- 17730814 TI - Vertical distribution and isotopic composition of living planktonic foraminifera in the Western north atlantic. AB - Thirteen species of planktonic foraminifera collected with vertically stratified zooplankton tows in the slope water, Gulf Stream cold core ring, and northern Sargasso Sea show significant differences in their vertical distributions in the upper 200 meters of these different hydrographic regimes. Gulf Stream cold core rings may be responsible for a southern displacement of the faunal boundary associated with the Gulf Stream when reconstructed from the deep-sea sediment record. Oxygen isotope analyses of seven species reveal that nonspinose species (algal symbiont-barren) apparently calcify in oxygen isotope equilibrium, whereas spinose species usually calcify out of oxygen isotope equilibrium by approximately -0.3 to -0.4 per mil in delta(18)O values. The isotope data indicate that foraminifera shells calcify in depth zones that are significantly narrower than the overall vertical distribution of a species would imply. PMID- 17730815 TI - The agulhas current during the late pleistocene: analysis of modern faunal analogs. AB - Analysis of micropaleontologic evidence in a deep-sea core in the south-west Indian Ocean indicates that the Agulhas Current was not a dominant feature of this region during glacial intervals. Interpretation of the fossil record, based on the analysis of modern faunal analogs, indicates that during glacial intervals the Agulhas Current was not the strong, year-round current that it is today. Evidence shows that during summer months a weak tropical current was present. During winter months the current was replaced by cool, high-salinity waters. This interpretation suggests that seasonal changes in circulation may have been more pronounced in the southwest Indian Ocean during glacial intervals than today. PMID- 17730816 TI - Dislocations in spinel and garnet high-pressure polymorphs of olivine and pyroxene: implications for mantle rheology. AB - The meteorite Tenham was observed by transmission electron microscopy and ringwoodite and majorite, the high-pressure polymorphs of olivine and pyroxene, were identified. Ringwoodite contains antiphase boundaries and straight dislocations that are probably dissociated. Mantle flow of spinel might proceed by pure climb, and whole-mantle convection may be possible if the grain size is small enough. PMID- 17730817 TI - Polarization of fucoid eggs by a calcium ionophore gradient. AB - When the eggs of the brown alga Pelvetia were grown in a gradient of the calcium ionophore A23187, they tended to form their rhizoidal outgrowths on the sides that were exposed to the higher concentration of ionophore. This result supports the hypothesis that the formation of an intracellular calcium gradient is an essential step in the polarization of these eggs; the rhizoid forms at the pole that has the higher concentration of calcium. PMID- 17730818 TI - ADDRESS OF THE PRESIDENT OF THE ROYAL SOCIETY. PMID- 17730819 TI - CRISIS IN RUBBER. PMID- 17730821 TI - THE SCHOOL OF DENTAL AND ORAL SURGERY OF COLUMBIA UNIVERSITY. PMID- 17730820 TI - AMERICAN LIBRARIES AND FOREIGN PERIODICALS. PMID- 17730822 TI - BEQUEST FOR THE ENDOWMENT OF THE TECHNICAL INSTITUTE OF NORTHWESTERN UNIVERSITY. PMID- 17730823 TI - DIVISION FOR EMERGENCY TRAINING AT THE UNIVERSITY OF MICHIGAN. PMID- 17730825 TI - MORE ABOUT "DEFORMATION OF ROCK STRATA BY EXPLOSIONS". PMID- 17730824 TI - FIGMENTS OF THE IMAGINATION. PMID- 17730827 TI - AUSTRALIAN COUNCIL FOR SCIENTIFIC AND INDUSTRIAL RESEARCH. PMID- 17730826 TI - VITAMIN C (ASCORBIC ACID) CONTENT OF THE BUFFALO-BERRY. PMID- 17730828 TI - SUBCLINICAL VITAMIN DEFICIENCY. PMID- 17730829 TI - VARIABILITY IN THE PAIN THRESHOLD. PMID- 17730831 TI - AN APPARATUS FOR DETERMINATION OF THE BACTERIAL CONTENT OF AIR. PMID- 17730830 TI - THE EFFECT OF SODIUM BICARBONATE ON THE THIAMINE CONTENT OF PEAS. PMID- 17730832 TI - THE BUILDING OF ATOMS AND THE NEW PERIODIC SYSTEM. PMID- 17730834 TI - THE FESTSCHRIFT OF SVANTE ARRHENIUS. PMID- 17730833 TI - THE DISRUPTION OF ATOMS BY ALPHA RAYS. PMID- 17730835 TI - THE DEATH OF LADY ALLARDYCE. PMID- 17730836 TI - SNOW DOUGHNUTS. PMID- 17730837 TI - A PROPOSAL OF TWO NEW MIOCENE FORMATIONAL NAMES. PMID- 17730838 TI - VARIATION OF FISHES ACCORDING TO LATITUDE. PMID- 17730839 TI - CONSTANTS AND VARIABLES IN BIOLOGY. PMID- 17730840 TI - THE TENNESSEE ACADEMY OF SCIENCE. PMID- 17730842 TI - SCIENCE NEWS. PMID- 17730841 TI - THE AMERICAN CHEMICAL SOCIETY-VI. PMID- 17730843 TI - METHODS TO FINANCE THE WORK OF THE ACADEMIES. PMID- 17730844 TI - THE TEMPLETON CROCKER EXPEDITION OF THE CALIFORNIA ACADEMY OF SCIENCES. PMID- 17730845 TI - HOTEL HEADQUARTERS AT ATLANTIC CITY. PMID- 17730846 TI - OBITUARY. PMID- 17730848 TI - A NEW DISEASE OF MOOSE. III. PMID- 17730847 TI - VITALISM, MECHANISM AND ORGANICISM. PMID- 17730849 TI - TWO BUSTS OF GREAT SCIENTIFIC MEN. PMID- 17730850 TI - CRYSTALLINE d-MANNURONIC ACID. PMID- 17730851 TI - A DEVICE FOR MEASURING THE MASS OF SMALL AQUATIC ANIMALS. PMID- 17730852 TI - EXPANDING THE TYPEWRITER. PMID- 17730853 TI - CELERY MOSAIC CONTROL IN FLORIDA BY ERADICATION OF THE WILD HOST COMMELINA NUDIFLORA. PMID- 17730854 TI - THE EFFECT OF THE ELECTROPURE PROCESS OF TREATING MILK UPON BACTERIAL ENDOSPORES. PMID- 17730856 TI - SCIENCE NEWS. PMID- 17730855 TI - DISSOCIATION OF CL. WELCHII. PMID- 17730857 TI - SCIENCE AND CIVILIZATION. PMID- 17730858 TI - BACTERIA AND THE ORIGIN OF SPECIES. PMID- 17730859 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17730860 TI - THE MOST PROBABLE VALUE OF CERTAIN BASIC CONSTANTS. PMID- 17730861 TI - THE NEED OF AN ENLARGED LIST OF BOTANICAL NOMINA CONSERVANDA. PMID- 17730862 TI - NEW YORK CITY AN ASEISMIC AREA. PMID- 17730863 TI - FACTORS THAT INFLUENCE LIFE AND GERMINATION OF COTTON SEED. PMID- 17730864 TI - COLLECTING AMPHIOXUS. PMID- 17730865 TI - CHONDRIOSOMES AND GOLGI APPARATUS IN PLANT CELLS. PMID- 17730866 TI - THE EFFECT OF HELIUM ON THE INTENSITY OF THE MERCURY SPECTRUM. PMID- 17730867 TI - SECTION C, CHEMISTRY. PMID- 17730868 TI - SECTION H--ANTHROPOLOGY. PMID- 17730869 TI - CHARLES EMERSON BEECHER. PMID- 17730870 TI - CONSVOCATION WEEK. PMID- 17730871 TI - OUR FUTURE 'PUBLIC ANALYSTS.'. PMID- 17730872 TI - THE MISUSE OF 'FORMATION' BY ECOLOGISTS. PMID- 17730873 TI - ON TITLES FOR PAPERS. PMID- 17730875 TI - NOTES ON ENTOMOLOGY. PMID- 17730874 TI - ELLIPTICAL HUMAN RED CORPUSCLES. PMID- 17730876 TI - THE EIGHTH INTERNATIONAL GEOGRAPHIC CONGRESS, WASHINGTON, 1904. PMID- 17730877 TI - THE SIXTH INYTERNATIONAL CONGRESS OF ZOOLOGY. PMID- 17730878 TI - THE DEDICATION OF PALMER HALL, COLORADO COLLEGE. PMID- 17730879 TI - THE STUDY OF SCIENCE. PMID- 17730880 TI - THE CULTURAL VALUE OF ZOOLOGY. PMID- 17730881 TI - THE VALUE OF SCIENTIFIC GENEALOGY. PMID- 17730883 TI - PREPAREDNESS FOR PEACE. PMID- 17730882 TI - THE EUGENICS MOVEMENT AS A PUBLIC SERVICE. PMID- 17730884 TI - JOHN MUIR. PMID- 17730886 TI - ANOTHER APPLIED BOTANY BOOK. PMID- 17730885 TI - DISCUSSION AND CORRESPONDENCE. PMID- 17730887 TI - A FOURTH MALLOPHAGAN SPECIES FROM THE HOATZIN. PMID- 17730888 TI - THE TOXICITY OF INSECTICIDES. PMID- 17730889 TI - THE AMERICAN SOCIETY OF NATURALISTS. PMID- 17730890 TI - AMERICAN SOCIETY FOR EXPERIMENTAL PATHOLOGY. PMID- 17730891 TI - Letters to the editor. PMID- 17730892 TI - Letters to the editor. PMID- 17730893 TI - World food shortage. PMID- 17730894 TI - Mycoplasma contamination. PMID- 17730895 TI - Thermal energy units. PMID- 17730896 TI - Letters to the editor. PMID- 17730897 TI - The decline of merit. PMID- 17730899 TI - Scientific manpower employment: so far, it seems to be holding up. PMID- 17730898 TI - World climates and food supply variations. AB - Most areas of famine could be greatly reduced with proper planning. Improvements in food production in nearby relatively favorable areas could alleviate the present situation whereby a disastrous food shortage must become "newsworthy" throughout the world before the ponderous machinery of international assistance and very expensive intercontinental staple grain shipments are made. Such planning would allow man to be far less at the mercy of the annual whims of seasonal weather for his food supply. PMID- 17730900 TI - Minutes to midnight for bulletin? PMID- 17730901 TI - Controversy over New Pesticide Regulations. PMID- 17730902 TI - World food conference: amid politicking, some progress. PMID- 17730903 TI - GAO Calls Security Lax at Nuclear Plants. PMID- 17730904 TI - Inventor's Suit Could Break New Ground. PMID- 17730905 TI - RANN Remiss in Reporting out Results. PMID- 17730906 TI - Two new particles found: physicists baffled and delighted. PMID- 17730907 TI - Particle search ends in an amazing coincidence. PMID- 17730908 TI - Exploring the Solar System (III): Whence the Moon? PMID- 17730910 TI - Annual meeting. PMID- 17730909 TI - X-ray Crystallography: A Refinement of Technique. PMID- 17730911 TI - Office of opportunities in science. PMID- 17730912 TI - Communications department. PMID- 17730914 TI - Io: a surface evaporite deposit? AB - A model is suggested for Io's surface composition involving evaporite salt deposits, rich in sodium and sulfur. According to this model, these deposits were produced as a result of the migration of salt-saturated aqueous solutions to Io's surface from a warm or hot interior followed by loss of the water to space. This model satisfies cosmochemical constraints based on Io's initial composition, current density, and thermal history. Salt-rich assemblages are easily derivable from the leaching of carbonaceous chondritic material; the chemical and optical properties of such deposits, after modification by irradiation, can be used to explain Io's overall albedo and spectral reflectance, its dark reddish poles, and the observed sodium emission as well as or better than other currently suggested materials. PMID- 17730913 TI - Transcontinental baselines and the rotation of the Earth measured by radio interferometry. AB - Nine separate very-long-baseline interferometry (VLBI) experiments, carried out in 1972 and 1973 with radio telescopes 3900 kilometers apart, yielded values for the baseline length with a root-mean-square deviation about the mean of less than 20 centitneters. The corresponding fractional spread is about five parts in 10(8). Changes in universal time and in polar motion were also detertnined accurately from these data; the root-mean-square scatter of these results with respect to those based on optical methods were 2.9 milliseconds and 1.3 meters, respectively. Solid-earth tides were apparently detected, but no useful estimate of their amplituide was extracted. PMID- 17730915 TI - Modeling periodically surging glaciers. AB - A numerical model has been developed which produces periodic surging as a characteristic of some glaciers for a certain accumulation and bedrock distribution in contrast to the normal steady state for nonsurging glaciers. Results are presented to illustrate how the magnitude of changes in the length, thickness, and velocity of surging glaciers can be simulated by the model. PMID- 17730916 TI - Amorphous Solid Water: An X-ray Diffraction Study. AB - Water vapor that condenses on a metal surface at 10 degrees K forms a noncrystalline phase of estimated density 1.2 grams per cubic centimeter. X-ray diffraction data of high precision and resolution have been analyzed to yield oxygen atom pair correlation functions. The positional correlation in amorphous solid water extends over only a few molecular radii, and the radial distribution of nearneighbor oxygen atoms in amorphous solid water is qualitatively different from that found in the low-pressure ice modifications. Amorphous solid water is a useful material for liquid water models because it can be studied under conditions such that the effects of static disorder and thermal excitation can be separated. PMID- 17730917 TI - Hemoglobin kinetics and the effect of organic phosphates. AB - A kinetic model based on allosteric mechanisms of cooperativity fits the experimentally observed phosphate dependence of hemoglobin reactions. Subunit inequivalence is found to be important in analyzing hemoglobin kinetics. The observed increase in the rate of deoxygenation in the presence of organic phosphates is primarily related to the increased rate of dissociation of the second oxygen molecule. PMID- 17730918 TI - PROGRESS IN FORESTRY UNDER STATE CONTROL. PMID- 17730919 TI - GEOLOGY AND GEOGRAPHY AT THE AMERICAN ASSOCIATION. PMID- 17730920 TI - THE NEW CHEMICAL LABORATORY OF THE UNIVERSITY OF KANSAS. PMID- 17730921 TI - A GASOLINE LAUNCH FOR FIELD WORK. PMID- 17730923 TI - YELLOW FEVER AND MOSQUITOES. PMID- 17730922 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17730924 TI - UNINSULATED CONDUCTORS AND SCIENTIFIC INSTRUMENTS. PMID- 17730926 TI - The blind technique. PMID- 17730927 TI - The price of books. PMID- 17730928 TI - Trees. PMID- 17730925 TI - Objectives of agricultural research. PMID- 17730929 TI - Science and man in the americas. PMID- 17730930 TI - White house foes: wiesner target of proposal to cut m.I.T. Funds. PMID- 17730932 TI - Science writing prize. PMID- 17730931 TI - APA: Psychiatrists Reluctant to Analyze Themselves. PMID- 17730933 TI - AAAS in Mexico: Inter-American Goodwill but Little Press Coverage. AB - This summer, in cooperation with the Mexican government's National Council of Science and Technology, the AAAS marked its 125th anniversary with a special meeting in Mexico City, the association's first in Latin America. For the occasion, News and Comment asked Edward Edelson, a science writer for the New York Daily News who has covered previous AAAS meetings, to review the Mexico City gathering from a reporter's point of view. A second article by Robert Gillette of the News and Comment staff will elaborate on the objectives of the meeting and on the difficulties of organizing a major international conference. PMID- 17730934 TI - AMA: Major Issues Draw Only Moderate Debate. PMID- 17730935 TI - Nuclear Tests: France's Unwelcome Export to the South Pacific. PMID- 17730936 TI - Science in Mexico (I): the revolution seeks a new ally. AB - Due to a typographical error in the 15 June issue of Science (column 1, fourth line from the bottom, page 1152), the dates of the Mexican Revolution were incorrectly given as 1910-1970; the correct dates are 1910-1917. In the 21 June issue (column 1, paragraph 1, page 1263), the number of technicians and engineers Mexico intends to send abroad for training this year was given as 200; the correct number is 2000. PMID- 17730937 TI - Catecholamine uptake in cerebral cortex: adaptive change induced by fighting. AB - The name of the senior author of "Catecholamine uptake in cerebral cortex: an adaptive change induced by fighting" (8 June 1973, page 1050) was misspelled. It should be Edith D. Hendley and not Edith D. Henley. PMID- 17730938 TI - Evaluation of instruction. AB - In "Evaluation of instruction" by Peter K. Gessner [11 May 1973, p. 569], sentence 4, paragraph 2, column 1, should read as follows: "It would seem likely that such an evaluative device would not differentiate between students able to solve the first problem presented to them and those who, although they may have been able to solve the fifth problem variant presented to them, failed to solve the first four." PMID- 17730939 TI - Trace elements: a growing appreciation of their effects on man. PMID- 17730940 TI - Large-scale variations in the obliquity of Mars. AB - Large-scale variations in the obliquity of the planet Mars are produced by a coupling between the motion of its orbit plane due to the gravitational perturbations of the other planets and the precession of its spin axis which results from the solar torque exerted on the equatorial bulge of the planet. The obliquity oscillates on a time scale of approximately 1.2 x 10(5) years. The amplitude of this oscillation itself varies periodically on a time scale of 1.2 X 10(6) years. The present-day obliquity is approximately 25.1 degrees. The maximum possible variation is from about 14.9 to 35.5 degrees. Signtificant climatic effects must be associated with the phenomenon. PMID- 17730941 TI - An equatorial jet in the Indian ocean. AB - At the surface of the Indian Ocean along the equator a narrow, jet-like current flows eastward at high speed during both transition periods between the two monsoons. The formation of the jet is accompanied by thermocline uplifting at the western origin of the jet and by sinking at its eastern terminus. This demonstrates that a time-variable current can have profound effects in changing the mass structure in the ocean. PMID- 17730943 TI - SCIENCE NEWS. PMID- 17730942 TI - Cadmium: mode of occurrence in illinois coals. AB - The cadmium content of 23 Illinois coals ranges from less than 0.3 to 28 parts per million. The higher cadmium contents are found in coals that also have a relatively high zinc content. Cadmium occurs in these coals in solid solution, replacing zinc in the mineral sphalerite (ZnS). The ratios of zinc to cadmium in sphalerites are similar to the ratios of zinc to cadmium in the whole coals from which the sphalerites were separated. PMID- 17730944 TI - A LOOK AHEAD. PMID- 17730945 TI - JOSEPH PRIESTLEY. PMID- 17730946 TI - JAMES ALEXANDER LYMAN. PMID- 17730947 TI - THE DISCOVERY OF THE INSECTICIDAL PROPERTY OF CARBON DISULPHIDE. PMID- 17730948 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17730949 TI - A NEW LONGEVITY RECORD. PMID- 17730951 TI - SYMBOLS FOR MUTATIONS IN MICE. PMID- 17730952 TI - THE VENOM OF NEW BORN PIT VIPERS. PMID- 17730950 TI - EDUCATION IN MANITOBA. PMID- 17730954 TI - A PRESERVING FLUID FOR GREEN PLANTS. PMID- 17730953 TI - RESOLUTIONS CONCERNING GEOPHYSICS. PMID- 17730955 TI - A BINOCULAR MAGNIFIER FOR THE DETERMINATION OF OPAQUE MINERALS. PMID- 17730957 TI - THE USE OF PLASTICINE MODELS IN TEACHING MITOSIS. PMID- 17730956 TI - THE RING METHOD FOR THE DETERMINATION OF SURFACE TENSION. PMID- 17730958 TI - THE CHROMOSOMES OF RODENTS. PMID- 17730960 TI - NATIONAL ACADEMY OF SCIENCES: Abstracts of Papers Presented at the Autumn Meeting, November 9-11, 1953 Massachusetts Institute of Technology, Cambridge, Massachusetts. PMID- 17730959 TI - Meetings & Conferences. PMID- 17730961 TI - Friends of Pleistocene Glacial Geology Field Meeting, Ayer Quadrangle, Massachusetts. PMID- 17730963 TI - INDIAN PRESERVES. PMID- 17730962 TI - DEAF-MUTES: THEIR INTERMARRIAGE AND OFFSPRING. PMID- 17730965 TI - MEN WHO ARE WORKING WITH KOCH. PMID- 17730964 TI - A BOSTON "ZOO.". PMID- 17730966 TI - HEALTH MATTERS. PMID- 17730967 TI - Cyclones and Areas of High Pressure. PMID- 17730968 TI - Questions of Nomenclature. PMID- 17730970 TI - THE LABELLING OF FAIR EXHIBITS AS AN AID TO AGRICULTURAL PRODUCTION. PMID- 17730969 TI - THE ORGANIZATION OF THE MEDICAL PROFESSION FOR WAR. PMID- 17730971 TI - PYRHELIOMETRY AND SOLAR RADIATION. PMID- 17730972 TI - REPLY TO PROFESSOR WILDER. PMID- 17730973 TI - OUR NATIONAL FLOWER. PMID- 17730974 TI - POST-GLACIAL CONTINENTAL UPLIFT. PMID- 17730975 TI - THE AMERICAN PHILOSOPHICAL SOCIETY. PMID- 17730976 TI - Metrically speaking. PMID- 17730977 TI - Metrically speaking. PMID- 17730979 TI - Unsolvable problems in mathematics. PMID- 17730978 TI - Metrically speaking. PMID- 17730980 TI - Facile optimism. PMID- 17730981 TI - Altruism in mountain bluebirds? PMID- 17730982 TI - Altruism in mountain bluebirds? PMID- 17730983 TI - What is agricultural research? PMID- 17730984 TI - National Science Foundation: Criticism from Conlan, GAO. PMID- 17730985 TI - Color additives: is successor to red dye no. 2 any safer? PMID- 17730986 TI - Science Adviser's Powers at Issue. PMID- 17730988 TI - Estrogen drugs: do they increase the risk of cancer? PMID- 17730987 TI - Pest Control: NAS Panel Warns of Possible Technological Breakdown. PMID- 17730989 TI - Estrogens and the FDA. PMID- 17730990 TI - Moving boundary problems: advances on several fronts. PMID- 17730991 TI - Sorting out a populace. PMID- 17730992 TI - Prehistoric craftsmanship. PMID- 17730994 TI - Sexual diversities. PMID- 17730993 TI - Differentiating cells. PMID- 17730995 TI - Cell biophysics. PMID- 17730996 TI - Hydrocarbons in open ocean waters. AB - Nonvolatile hydrocarbons in Atlantic Ocean and nearby waters were found to contain aromatics at lower concentrations than would be expected if the source of the hydrocarbons were crude oil or petroleum refinery products. Hydrocarbons appear to persist in the water to varying degrees with the most persistent being the cycloparaffins, then the isoparaffins, and finally the aromatics. PMID- 17730997 TI - Mineral inclusions in diamond: temperature and pressure of equilibration. AB - Two distinct suites of minerals included in natural diamond occur and probably represent different physical and chemical conditions during diamond growth. Minerals of the ultramafic suite appear to have equilibrated in the range 1000 degrees to 1300 degrees C between 45 and 65 kilobars, whereas the temperature range for minerals of the eclogitic suite is 850 degrees to 1250 degrees C. At present, models relating the partitioning of magnesium and iron between coexisting phases are not sufficiently rigorous to determine a value for the pressure of equilibration of these eclogitic suite inclusions. PMID- 17730998 TI - High-pressure physics: the 1-megabar mark on the ruby r1 static pressure scale. AB - Ruby crystals were subjected to a static pressure greater than 1 megabar in a diamond-windowed pressure cell. The pressure was monitored continuously by observing the spectral shift of the sharp fluorescent R(1) ruby line excited with a cadmium-helium gas-diffusion laser beam. One megabar appears to be the highest pressure ever reported for a static experiment in which an internal calibration was employed. PMID- 17730999 TI - Reproductive and vegetative morphology of a cretaceous angiosperm. AB - Recent collections from plant-bearing deposits of Cenomanian age in central Kansas have yielded angiosperm axes with helically arranged, seed-bearing, conduplicate carpels. Large leaves associated with these fruits are thought to represent parts of the same kind of plant because the leaves and fruits are the only plant fossils at this locality to have distinctive, morphologically identical, yellow bodies within their carbonaceous remains. These fossils provide a rare opportunity to study the morphology of an ancient angiosperm and illustrate the antiquity of certain features considered primitive by comparative angiosperm morphologists. PMID- 17731001 TI - PRODUCTS and MATERIALS. PMID- 17731000 TI - Unsteady state denudation. PMID- 17731002 TI - A PLEA FOR THE BROADER EDUCATION OF THE CHEMICAL ENGINEER. PMID- 17731004 TI - THE INFLUENCE OF FRICTION IN ECONOMICS. PMID- 17731003 TI - THE MECHANISM OF HEREDITY. PMID- 17731005 TI - THE NOBEL PRIZES. PMID- 17731007 TI - THE FOSSIL SAWFLY PERGA COLORADENSIS. PMID- 17731006 TI - UNIVERSITY REGISTRATION. PMID- 17731008 TI - ANOTHER FLEA REMEDY. PMID- 17731010 TI - THE AMERICAN SOCIETY OF AGRONOMY. PMID- 17731009 TI - THE SORGHUM MIDGE. PMID- 17731011 TI - TWELFTH ANNUAL MEETING OF THE NATIONAL ASSOCIATION OF STATE UNIVERSITIES. PMID- 17731012 TI - THE WORK OF THE MAGNETIC SURVEY YACHT "GALILEE" IN THE PACIFIC OCEAN DURING 1907. PMID- 17731013 TI - ELIZABETH THOMPSON SCIENCE FUND. PMID- 17731015 TI - CHARLES FAY WHEELER. PMID- 17731014 TI - THE NEW PURPOSE IN STATE DEVELOPMENT: THE SAFEGUARDING ITS OWN FUTURE. PMID- 17731016 TI - AMERICAN MATHEMATICAL PUBLICATIONS. PMID- 17731018 TI - HOME ECONOMICS. PMID- 17731017 TI - MATHEMATICS FOR ADMISSION TO COLLEGE. PMID- 17731019 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17731020 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17731021 TI - THE APPARENT SINKING OF ICE IN LAKES. PMID- 17731023 TI - THE FIGHT ON THE COLLEGES. PMID- 17731022 TI - THE EFFECTS OF DEFORESTATION IN NEW ENGLAND. PMID- 17731024 TI - ON THE GENERAL USE OF THE GRATING WITH THE INTERFEROMETER. PMID- 17731026 TI - NOTES ON AN EXPERIMENT CONCERNING THE NATURE OF UNIT CHARACTERS. PMID- 17731025 TI - SCIENTIFIC JOURNALS AND ARTICLES. PMID- 17731027 TI - TROUGH FAULTING IN THE SOUTHERN ADIRONDACKS. PMID- 17731028 TI - Progress in desalination. PMID- 17731029 TI - Biology editors' definition. PMID- 17731030 TI - Deterioration of teaching. PMID- 17731031 TI - Insightful amateur astronomer. PMID- 17731032 TI - Apollo 13: cost of abortion. PMID- 17731033 TI - Stable carbonium ions in solution. PMID- 17731034 TI - Environmental Law: Courts Demand DDT Action, Block Pipeline Road. PMID- 17731036 TI - Colorado Environmentalists: Scientists Battle AEC and Army. PMID- 17731038 TI - Finch Leaves HEW for Advisor's Post; Yolles Out at NIMH. PMID- 17731037 TI - Dissent spreads to nobelists, industrial scientists. PMID- 17731039 TI - The forces of nature: testing their strength. PMID- 17731040 TI - Visibility of single atoms. AB - Theoretical and experimental studies indicate that, with a high-resolution scanning electron microscope, it is now possible to obtain pictures of a single heavy atom resting on a thin carbon substrate. PMID- 17731041 TI - Jupiter's Convection and Its Red Spot. AB - Physical properties of the liquid hydrogen-helium layer of Jupiter are calculated and used in evaluating convection and in interpreting the approximately constant rate of longitudinal motion of the Red Spot on the basis of the Hide-Streett model. PMID- 17731042 TI - Quartz: preferred orientation in rocks produced by dauphine twinning. AB - X-ray analyses of quartz aggregates deformed in the laboratory andin nature show a striking difference in the preferred orientation of the positive and negative trigonal forms. These observations may be accounted for by mechanically induced Dauphine twinning. This orienting mechanism is unusual in that it requires no permanent strain. PMID- 17731043 TI - Diversity of planktonic foraminifera in deep-sea sediments. AB - The diversity of a planktonic foraminiferal assemblage on the ocean floor depends on the state of preservation of that assemblage. As dissolution progresses, species diversity (number of species in the assemblage) decreases, but compound diversity (based on relative species abundance) first increases and then decreases; species dominance first decreases and then increases. The reason for these changes is that the species most susceptible to solution deliver moresediment to the ocean floor than do species with solution-resistant shells, possibly because the more soluble tests are produced in surface waters, where growth and production are greatest. PMID- 17731044 TI - Miniature whirlwinds produced in the laboratory by high-voltage electrical discharges. AB - Laboratory experiments showed that under certain conditions of vorticity the electrical heatinig produced by a high-voltage discharge at atmospheric pressure can cause the formation of a miniature tornado-like vortex. Once it forms, this vortex stabilizes the electrical discharge along its axis and changes its character from that of a spark to high-pressure variety of a glow discharge. Electrical and dynamic parameters were measured. By relating observations and measurements made in these experiments to previous work and to analogous situations in nature, it is concluded that the heating produced by electrical discharges in a large storm may play a significant role in forming and maintaining natural tornadoes. PMID- 17731046 TI - Heavy carbon. PMID- 17731045 TI - Chemical individuality of lunar, meteoritic, and terrestrial silicate rocks. PMID- 17731047 TI - SCIENCE NEWS. PMID- 17731049 TI - OPENING OF THE CANADIAN NATIONAL RESEARCH LABORATORIES. PMID- 17731048 TI - BASIN RANGE TYPES. PMID- 17731050 TI - OBITUARY. PMID- 17731051 TI - LIGHT OR EXERCISE AS FACTORS IN SEXUAL PERIODICITY IN BIRDS? PMID- 17731052 TI - A NEW YELLOW PEROMYSCUS. PMID- 17731053 TI - SOME NEW AGAR DIGESTING BACTERIA. PMID- 17731054 TI - PROFESSOR TROLAND AND DR. KUNZ. PMID- 17731055 TI - AN ADJUSTABLE APPARATUS STAND AND TRUCK. PMID- 17731056 TI - A METHOD FOR MOUNTING SPECIMENS OF DROSOPHILA ON MICROSCOPIC SLIDES. PMID- 17731057 TI - GROWTH RATES AND RACIAL SIZE IN RABBITS AND BIRDS. PMID- 17731058 TI - CULTIVATION OF THE VIRUS OF INFECTIOUS LARYNGO-TRACHEITIS OF CHICKENS. PMID- 17731059 TI - ANTAGONISM AND PERMEABILITY. PMID- 17731060 TI - JOHN MUIR. PMID- 17731061 TI - DO THE FOWLER'S TOAD AND THE AMERICAN TOAD INTERBREED? PMID- 17731062 TI - NOTICE OF POSSIBLE SUSPENSION OF THE RULES OF NOMENCLATURE IN THE CASES OF HOLOTHURIA 1758 VS. PHYSALIA 1801, AND BOHADSCHIA 1833 VS. HOLOTHURIA 1791. PMID- 17731063 TI - THE POPULAR NAMES OF NORTH AMERICAN PLANTS. PMID- 17731064 TI - PROPULSION BY SURFACE TENSION. PMID- 17731065 TI - RECENT PROGRESS IN PALEONTOLOGY. PMID- 17731066 TI - THE REFLECTION OF ggr-RAYS BY CRYSTALS. PMID- 17731067 TI - The implications of sociobiology. PMID- 17731068 TI - The implications of sociobiology. PMID- 17731069 TI - The implications of sociobiology. PMID- 17731070 TI - The implications of sociobiology. PMID- 17731071 TI - Energy diplomacy. PMID- 17731073 TI - Seasonal variability in early hominid predation. PMID- 17731072 TI - United States uranium resources--an analysis of historical data. PMID- 17731074 TI - White house science office: house and senate agree on bill. PMID- 17731075 TI - Massachusetts Juvenile Justice: De-institutionalization on Trial. PMID- 17731077 TI - Venus: radar maps show evidence of tectonic activity. PMID- 17731076 TI - House chops sex-pot probe. PMID- 17731079 TI - Biology of transitional zones. PMID- 17731080 TI - Processes underlying vision. PMID- 17731078 TI - Cell biology: cell surfaces and the regulation of mitosis. PMID- 17731081 TI - Quantized fields. PMID- 17731082 TI - Symbiotic associations. PMID- 17731083 TI - Comparative species richness in fluctuating and constant environments: coral associated decapod crustaceans. AB - The number of decapod species associated with the coral Pocillopora damicornis is compared between two regions on the Pacific coast of Panama which are of the same geologic age but differ in environmental characteristics. The relationship between number of species and coral head size does not differ between the two regions but species composition among coral heads is more variable in the fluctuating environment. Thus there are more species (55 compared to 37) associated with corals in the fluctuating environment than in the constant environment. These data impugn the concept that environmental constancy increases species richness. They support the hypothesis that species equilibrium within habitats is maintained by measurable ecological factors-in this case, the effects of a natural physical disturbance. PMID- 17731084 TI - Ecological competition between algae: experimental confirmation of resource-based competition theory. AB - All possible outcomes of ecological competition, including stable coexistence, were observed in laboratory studies of two species of freshwater diatoms potentially limited by phosphate and silicate. The relative abundance of these nutrients determined the outcome of competition. The observed conditions of coexistence and competitive displacement agree with those predicted solely from the abilities of each species to acquire and utilize limiting nutrients. Coexistence occurred only when the growth rate of each species was limited by a different resource. These results may help explain the regional coexistence in nature of an otherwise paradoxically high number of algal species. PMID- 17731086 TI - HISTORY IN THE ARCHIVES OF THE ROYAL SOCIETY. PMID- 17731085 TI - Potassium-argon ages from the galapagos islands. AB - Potassium-argon ages of eight volcanic rocks from some of the geologically oldest flows exposed in the Galapagos Archipelago indicate that the Galapagos Islands have a probable maximum age of 3 million years. Rocks from six islands were dated; the oldest are from Espanola (3.2 +/- 0.2), Sante Fe (2.7 +/- 0.1), and Plazas (4.2 +/- 1.8 million years). The new data suggest that the Galapagos Islands are younger than previously supposed on the basis of marine magnetic anomaly dating, but they are older than most previously dated rocks from the Galapagos. PMID- 17731088 TI - CONSUMPTION OF TEOSINTE SEED BY BIRDS IN GUATEMALA. PMID- 17731087 TI - THE LUMINESCENCE OF ADHESIVE TAPE. PMID- 17731089 TI - GRAPTOLITES FROM HIGHGATE, VERMONT. PMID- 17731090 TI - MULL SOIL UNDER SPRUCE. PMID- 17731091 TI - JOINT SYMPOSIUM OF THE AMERICAN CHEMICAL SOCIETY, THE UNIVERSITY OF WISCONSIN AND THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17731092 TI - THE SYNTHESIS OF A POLYSACCHARIDE FROM GLUCOSE-1-PHOSPHATE IN MUSCLE EXTRACT. PMID- 17731093 TI - THE EFFECT OF ULTRA-VIOLET LIGHT ON BUILT-UP MULTILAYERS. PMID- 17731094 TI - A METHOD FOR ESTIMATING THE DEGREE OF MINERALIZATION OF BONES FROM TRACINGS OF ROENTGENOGRAMS. PMID- 17731095 TI - A THERMOREGULATOR AND RELAY ASSEMBLY. PMID- 17731096 TI - THE CONTRIBUTION OF MEDICAL SCIENCE TO MEDICAL ART AS SHOWN IN THE STUDY OF TYPHOID FEVER. PMID- 17731098 TI - A SCHOOL OF NURSING AND HEALTH AT THE UNIVERSITY OF CINCINNATI. PMID- 17731097 TI - CHARLES WILLARD HAYES. PMID- 17731099 TI - PRACTICAL WORK FOR STUDENTS OF THE NEW YORK STATE COLLEGE OF FORESTRY. PMID- 17731100 TI - STANFORD UNIVERSITY ARBORETUM. PMID- 17731101 TI - AN ENGINEER'S IDEA OF ENERGY. PMID- 17731103 TI - "TYPUS" AND "TYPE" IN TAXONOMY. PMID- 17731102 TI - "AVAILABLE ENERGY" VS. "ENERGY". PMID- 17731104 TI - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES. PMID- 17731106 TI - A NEW MITE FROM THE HAWAIIAN ISLANDS. PMID- 17731107 TI - THE OHIO ACADEMY OF SCIENCE. PMID- 17731105 TI - A POWER CHISEL FOR PALEONTOLOGIC LABORATORIES. PMID- 17731108 TI - EDUCATION AND EXPLORATION BY THE AMERICAN MUSEUM. PMID- 17731110 TI - ANSEL AUGUSTUS TYLER. PMID- 17731109 TI - THE NECESSITY OF BALANCING DIETARIES WITH RESPECT TO VITAMINES. PMID- 17731111 TI - SOME SIMPLIFICATION OF MICROSCOPICAL TECHNIQUE. PMID- 17731112 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17731113 TI - PROFESSOR KEYSER ON RUSSELL'S "THE ANALYSIS OF MIND". PMID- 17731114 TI - RUSSIAN SCIENTIFIC LITERATURE. PMID- 17731116 TI - THE CONTROL AND CURE OF PARATHYROID TETANY IN NORMAL AND PREGNANT ANIMALS. PMID- 17731115 TI - METHODS OF GERMAN PUBLISHERS. PMID- 17731117 TI - INFLUENCE OF H-ION ON GROWTH OF AZOTOBACTER. PMID- 17731118 TI - THE AMERICAN CHEMICAL SOCIETY. PMID- 17731119 TI - PRELIMINARY NOTES ON VAUXITE AND PARAVAUXITE. PMID- 17731120 TI - The Shortage of Scientific and Technical Personnel: What Industry Is Doing About It. PMID- 17731121 TI - The Scope of Science. PMID- 17731122 TI - On the Multiple Factor Theory of Respiratory Control as Outlined by Gray. PMID- 17731123 TI - Reply to Krueger's Criticism of the Multiple Factor Theory. PMID- 17731124 TI - Chemical Research Conferences, AAAS, 1947: Colby Junior College, New London, New Hampshire, June 16-August 22. PMID- 17731125 TI - COMMENTS by Readers. PMID- 17731126 TI - Effect of Intraperitoneal Injection of Malignant Urine Extracts in Normal and Hypophysectomized Rats. PMID- 17731127 TI - Serum Phosphatases and Alloxan Diabetes. PMID- 17731128 TI - The pH Stability of Viruses of Newcastle Disease and Fowl Plague. PMID- 17731129 TI - Effect of Gamma Globulin on Circulating Human Complement. PMID- 17731130 TI - False Disinfection Velocity Curves Produced By Quaternary Ammonium Compounds. PMID- 17731131 TI - The Maillard Reaction in Microbiological Assay. PMID- 17731133 TI - This week in science. PMID- 17731132 TI - A Simple Method for Rearing Blowflies Without Meat. PMID- 17731135 TI - Japan expands graduate, postdoc slots. PMID- 17731134 TI - Sciencescope. PMID- 17731136 TI - First light from a space laser. PMID- 17731137 TI - A science teaching system honed in a two-room school. PMID- 17731138 TI - Winning with testosterone. PMID- 17731139 TI - Wellcome to the big leagues. PMID- 17731140 TI - Physics restored at james madison u. PMID- 17731141 TI - More dead sea caves? PMID- 17731143 TI - Off-the-Shelf Chips Conquer The Heights of Computing. PMID- 17731142 TI - Computers '95: fluid dynamics. PMID- 17731144 TI - Mathematicians open the black box of turbulence. PMID- 17731145 TI - Keplerian complexity: numerical simulations of accretion disk transport. AB - Supercomputer simulations have been used in conjunction with analytic studies to investigate the central issue of astrophysical accretion-disk dynamics: the nature of the angular momentum transport. Simulations provide the means to investigate and experiment with candidate mechanisms, including global hydrodynamic instabilities, spiral shock waves, and local magnetohydrodynamic (MHD) instabilities. Simulations have demonstrated that accretion disks are generally MHD turbulent. These results suggest that the fundamental physical mechanism for angular momentum transport in accretion disks has now been identified. PMID- 17731146 TI - Turbulent dynamics in the solar convection zone. AB - Observations of the sun reveal highly complex flows and magnetic structures that must result from turbulent convection in the solar envelope. A remarkable degree of large-scale coherence emerges from the small-scale turbulent dynamics, as seen in the cycles of magnetic activity and in the differential rotation profile of this star. High-performance computing now permits numerical simulations of compressible turbulence and magnetohydrodynamics with sufficient resolution to show that compact structures of vorticity and magnetic fields can coexist with larger scales. Such structured turbulence is yielding transport properties for heat and angular momentum at considerable variance with earlier models. These simulations are elucidating the coupling of turbulent fluid motions with rotation and magnetic fields, which must control the interlinked differential rotation and magnetic dynamo action. PMID- 17731147 TI - Modeling ocean circulation. AB - Ocean numerical models have become quite realistic over the past several years as a result of improved methods, faster computers, and global data sets. Models now treat basin-scale to global domains while retaining the fine spatial scales that are important for modeling the transport of heat, salt, and other properties over vast distances. Simulations are reproducing observed satellite results on the energetics of strong currents and are properly showing diverse aspects of thermodynamic and dynamic ocean responses ranging from deep-water production to EI Nino. Now models can represent not only currents but also the consequences for climate, biology, and geochemistry over time spans of months to decades. However, much remains to be understood from models about ocean circulation on longer time scales, including the evolution of the dominant water masses, the predictability of climate, and the ocean's influence on global change. PMID- 17731148 TI - Numerical models of caldera-scale volcanic eruptions on Earth, venus, and Mars. AB - Volcanic eruptions of gassy magmas on Earth, Venus, and Mars produce plumes with markedly different fluid dynamics regimes. In large part the differences are caused by the differing atmospheric pressures and ratios of volcanic vent pressure to atmospheric pressure. For each of these planets, numerical simulations of an eruption of magma containing 4 weight percent gas were run on a workstation. On Venus the simulated eruption of a pressure-balanced plume formed a dense fountain over the vent and continuous pyroclastic flows. On Earth and Mars, simulated pressure-balanced plumes produced ash columns, ash falls, and possible small pyroclastic flows. An overpressured plume, illustrated for Mars, exhibited a complex supersonic velocity structure and internal shocks. PMID- 17731149 TI - Computational materials design with first-principles quantum mechanics. PMID- 17731150 TI - Macroscopic evidence of the effect of interfacial slippage on adhesion. AB - The adhesion strengths of a viscoelastic adhesive were measured on various substrates that were prepared by grafting silanes bearing organic functional groups to silicon wafers. Conventional theories predict that adhesion should be proportional to the surface free energy of the substrate; but adhesion on a fluorocarbon surface was significantly greater than on some of the hydrocarbon surfaces, although the fluorocarbon surface has the lowest surface free energy. This result could be explained by invoking a model of adhesion based on the slippage of the adhesive at the interface. PMID- 17731151 TI - Synchrony and causal relations between permian-triassic boundary crises and siberian flood volcanism. AB - The Permian-Triassic boundary records the most severe mass extinctions in Earth's history. Siberian flood volcanism, the most profuse known such subaerial event, produced 2 million to 3 million cubic kilometers of volcanic ejecta in approximately 1 million years or less. Analysis of (40)Ar/(39)Ar data from two tuffs in southern China yielded a date of 250.0 +/- 0.2 million years ago for the Permian-Triassic boundary, which is comparable to the inception of main stage Siberian flood volcanism at 250.0 +/- 0.3 million years ago. Volcanogenic sulfate aerosols and the dynamic effects of the Siberian plume likely contributed to environmental extrema that led to the mass extinctions. PMID- 17731152 TI - Short-and Intermediate-Range Structural Ordering in Glassy Boron Oxide. AB - Ordering at short-length scales is a universal feature of the glassy state. Experiments on boron oxide and other materials indicate that ordering on mesoscopic-length scales may also be universal. The high-resolution nuclear magnetic resonance (NMR) measurements of oxygen in boron oxide glass presented here provide evidence for structural units responsible for ordering on short- and intermediate-length scales. At the molecular level, planar BO(3/2) units accounted for the local ordering. Oxygen-17 NMR spectra resolved detailed features of the inclusion of these units in boroxol rings, oxygen bridging two rings, and oxygen shared between two nonring BO(3/2) units. On the basis of these and corroborative boron-11 NMR and scattering results, boron oxide glass consists of domains that are rich or poor in boroxol rings; these domains are proposed to be the structural basis of intermediate-range order in glassy boron oxide. PMID- 17731153 TI - Branched threadlike micelles in an aqueous solution of a trimeric surfactant. AB - Very long threadlike micelles observed in aqueous solutions of some surfactants have attracted much attention because of the peculiar rheological properties of these systems. Molecular dynamics simulations have suggested that branched threadlike micelles should exist in concentrated solutions of dimeric surfactants. Here experimental evidence, obtained from transmission electron microscopy at cryogenic temperature, is presented of branched threadlike micelles in aqueous solutions of a triquaternary ammonium (trimeric) surfactant made up of three amphiphilic moieties connected at the level of the head-groups by two propanediyl spacers. PMID- 17731154 TI - Vignette: changing times. PMID- 17731155 TI - The enola gay script. PMID- 17731156 TI - Products & materials. PMID- 17731157 TI - The MX Question. PMID- 17731158 TI - The MX Question. PMID- 17731159 TI - Equity and economics. PMID- 17731160 TI - Equity and economics. PMID- 17731161 TI - U.s.-Soviet relations. PMID- 17731162 TI - Science funding in west Germany. PMID- 17731164 TI - An alternative funding mechanism. PMID- 17731163 TI - U.s.-Soviet relations. PMID- 17731166 TI - Dark days for social research. PMID- 17731168 TI - Reagan budget would reshape science policies. PMID- 17731165 TI - Energy supply interruptions and national security. AB - Vulnerability to oil supply interruptions poses serious threats to the U.S. economy and the life-style of its citizens. The Iranian cutbacks in 1979 resulted in price increases of 120 percent in 1 year and gasoline lines across the country. Creation and use of ample public and private stocks could moderate price increases after another interruption and prevent disruption of supplies. Use of the marketplace to allocate shortages, coupled with rebates to cushion blows to the economy and hardship to individuals, would be eminently more efficient than government allocation programs. International cooperation, through coordination of stock buildup and withdrawal, could mitigate the damage from oil disruptions among all the Western nations. PMID- 17731167 TI - Reagan to Keep OSTP and CEQ. PMID- 17731169 TI - Federal job exam to be retired. PMID- 17731170 TI - New university law decreed in chile. PMID- 17731172 TI - Reagan selects new OSHA director. PMID- 17731171 TI - Export of hazardous goods raises congressional ire. PMID- 17731173 TI - Nobel follies. PMID- 17731174 TI - Solving Louisville's Friday the 13th Explosion. PMID- 17731175 TI - Electron microscope center opens at berkeley. PMID- 17731177 TI - Cell defect in mental retardation. PMID- 17731176 TI - Caffeine's Stimulatory Effects Explained. PMID- 17731178 TI - Prehistory in the tropics. PMID- 17731179 TI - Micropaleontology. PMID- 17731180 TI - Paleoclimates. PMID- 17731181 TI - Biomechanics. PMID- 17731182 TI - Oxygen isotope ratios in trees reflect mean annual temperature and humidity. AB - Values of the oxygen isotope ratios (delta(18)O) in tree-ring cellulose closely reflect the delta(18)O values in atmospheric precipitation and hence mean annual temperature. The change in delta(18)O in cellulose is 0.41 per mil per degree Celsius for selected near-coastal stations. The values of delta(18)O in precipitation and cellulose also change with altitude, as demonstrated for Mount Rainier, Washington. A temperature lapse rate of 5.2 degrees +/- 0.5 degrees C per 1000 meters calculated from cellulose delta(18)O values agrees with the accepted mean annual lapse rate of 5 degrees C per 1000 meters for this region. Cellulose delta(18)O values and delta(18)O values of carbon dioxide equilibrated with leaf water differ by a fixed 16 per mil. PMID- 17731183 TI - Volcanic origin of the eruptive plumes on io. AB - A quadruple long exposure of Io in eclipse exhibits faint auroral emission from the eruptive plumes. No luminous spots in the vents, predicted by Gold, were observed. Heat from the interior of Io appears to be the predominant source of energy in the plumes. PMID- 17731184 TI - Reworked neritic fossils in upper mesozoic and cenozoic central pacific deep-sea sediments monitor sea-level changes. AB - Upper Mesozoic and Cenozoic pelagic sediments in the central Pacific Ocean contain occasional horizons with reworked and displaced fossils produced by organisms that once lived in neritic shallow-water environments. The flux of neritic fossils was restricted to eight intervals of low eustatic sea level during Late Mesozoic and Cenozoic times. They were eroded from shoals along the flanks of volcanic highs which often supported tropical islands and which since then have subsided. PMID- 17731185 TI - Stable lead isotopes as a tracer in coastal waters. AB - The natural abundances of the stable isotopes of lead are used to identify natural and industrial sources of lead in the coastal waters of British Columbia, Canada. The (206)Pb/(207)Pb ratios, used to characterize the lead source, had values of approximately 1.24 for coastal oceanic water, approximately 1.22 for fjord waters receiving lead from mine tailings, and approximately 1.163 for waters near urban centers. The lead concentration data are in agreement with presently accepted seawater values. PMID- 17731186 TI - PRODUCTS and MATERIALS. PMID- 17731187 TI - SCIENCE NEWS. PMID- 17731188 TI - EMERGENT EVOLUTION AND HYBRIDISM. PMID- 17731190 TI - BRANCHING HABITS OF THE HEVEA RUBBER TREE. PMID- 17731189 TI - BIBLIOCHRESIS: THE PILOT OF RESEARCH. PMID- 17731191 TI - A SACRIFICE TO PELE. PMID- 17731192 TI - OESTRUS FOLLOWING THE REMOVAL OF ONE OVARY. PMID- 17731193 TI - WHAT IS CONTROL? PMID- 17731194 TI - PROFESSIONAL ETHICS AND THE ARTIST. PMID- 17731195 TI - A NEW RECORD OF CASTOROIDES OHIOENSIS FROM ILLINOIS. PMID- 17731196 TI - STATEMENT IN REGARD TO PROFESSOR EINSTEIN'S PUBLICATIONS. PMID- 17731197 TI - CONFERENCE AT CHICHEN ITZA. PMID- 17731199 TI - ELIMINATING OPAQUING BY ALTERNATING BLACK AND WHITE BACKGROUNDS WHILE MAKING A PHOTOGRAPH. PMID- 17731198 TI - LABORATORY AND TEACHING DEVICES MADE FROM PLASTER OF PARIS. AB - A method has been described whereby models of septic tanks for teaching public health and oncometers for physiological demonstration and research may be constructed by employing a wire frame and covering it with plaster of Paris These models should prove especially useful to teachers in rural and suburban communities and to extension workers whose task it is to keep a vast number of our population informed as to the best measures of protecting their health These models may be rendered impervious to air and water by means of paraffin, varnish or brushing lacquer. PMID- 17731200 TI - COMPONENTS OF AIR IN RELATION TO ANIMAL LIFE. PMID- 17731202 TI - Publications Received. PMID- 17731201 TI - SOME CONSTITUENTS OF DERRIS AND "CUBE" ROOTS OTHER THAN ROTENONE. PMID- 17731203 TI - Meetings & Conferences. PMID- 17731205 TI - The Ninth International Congress of Genetics. PMID- 17731204 TI - International Congress on Cosmic Radiation at Bagneres de Bigorre. PMID- 17731206 TI - The "Great Fireball Procession" of 1913. PMID- 17731208 TI - SCIENCE NEWS. PMID- 17731207 TI - Methionine Content of Teosinte. PMID- 17731209 TI - RESEARCH, AN EDUCATIONAL ASSET. PMID- 17731211 TI - THE FIFTH NEW YORK MEETING OF THE AMERICAN ASSOCIATION AND ASSOCIATED SOCIETIES. PMID- 17731210 TI - THE NEED FOR TRAINING TAXONOMIC BOTANISTS. PMID- 17731213 TI - ON THE ANTIQUITY OF RELICS OF MAN AT FREDERICK, OKLAHOMA. PMID- 17731214 TI - A NOTE ON THE FLUORESCENCE OF TEETH IN ULTRA-VIOLET RAYS. PMID- 17731212 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17731215 TI - MORE DATA. PMID- 17731216 TI - ONE HUNDRED PER CENT. HATCH. PMID- 17731217 TI - MOUNTING CHICK EMBRYOS. PMID- 17731218 TI - COLOR DISCS USED IN SOIL COLOR ANALYSIS. PMID- 17731219 TI - LIVING CELLS TWO AND A HALF CENTURIES OLD. PMID- 17731221 TI - Synthesis gas: a raw material for industrial chemicals. AB - Rapid increases in the price of imported crude oil have accelerated a shift in the raw material base for chemical feedstocks from natural gas to crude oil to coal. Widespread use of ethylene as a feedstock has depended on the availability at attractive prices of natural gas and petroleum. As the resource base shifts from natural gas and petroleum to coal, ethylene is being replaced by synthesis gas (a mixture of hydrogen and carbon monoxide of varying composition), which can be manufactured directly from any of these carbonaceous sources. This trend is expected to accelerate in the 1980's. Organics likely to be produced from synthesis gas include ethanol, ethylene glycol, and vinyl acetate. PMID- 17731220 TI - Affinities between scientists and humanists. PMID- 17731222 TI - Impact on agriculture of the mount st. Helens eruptions. AB - Ash from Mount St. Helens has fallen over a diverse agricultural area, with deposits of up to 30 kilograms per square meter. Crop losses in eastern Washington are estimated at about $100 million in 1980-about 7 percent of the normal crop value in the affected area and less than was expected initially. Production of wheat, potatoes, and apples will be normal or above normal because the favorable conditions for growth of these crops since the ashfall helped offset the losses. Alfalfa hay was severely lodged under the weight of the ash, but ash-contaminated hay is apparently nontoxic when eaten by livestock. The ash as an abrasive is lethal to certain insects, such as bees and grasshoppers, but populations are recovering. The ash has increased crop production costs by necessitating machinery repairs and increased tillage. On soil, the ash reduces water infiltration, increases surface albedo, and may continue to affect water runoff, erosion, evaporation, and soil temperature even when tilled into the soil. Ash on plant leaves reduced photosynthesis by up to 90 percent. Most plants have tended to shed the ash. With the possible exception of sulfur, the elements in the ash are either unavailable or present in very low concentrations; and no significant contribution to the nutrient status of soils is expected. PMID- 17731224 TI - An Early Test of Reagan's Economics. PMID- 17731223 TI - The hawaii to tahiti shuttle experiment. AB - The Shuttle Experiment conducted between Hawaii and Tahiti from January 1979 to June 1980 was designed to observe the changing equatorial ocean structure and circulation, to study the variations and interactions of the four major equatorial ocean currents, and to develop a scientific basis for their monitoring by simple observations of thermal structure and sea level. Preliminary analyses of the results show that the equatorial thermal structure remains intact during a normal year and that only the positions and intensities of the currents are subject to change. The water transport of the equatorial undercurrent varied from 25 x 10(6) cubic meters per second in January to 51 x 10(6) cubic meters per second in July, but also exhibited strong short-term pulsations. The equatorial surface flow responded strongly to the winds at periods of 1 month and longer. An array of drifter buoys in the equatoral countercurrent was subject to very little dispersion while traveling over 4500 kilometers in 4 months. Low-frequency fluctuations in the North Equatorial Countercurrent can be monitored by means of the difference in sea level between Fanning and Majuro. PMID- 17731226 TI - Dinosaur battle erupts in british museum. PMID- 17731225 TI - Pentagon orders end to computer babel. PMID- 17731227 TI - Joint research guidelines for industry. PMID- 17731229 TI - Long-awaited changes made in patent law. PMID- 17731228 TI - Second gene splicer to go public. PMID- 17731230 TI - Anti-nuclear war consciousness raising. PMID- 17731231 TI - Biology and culture meet in milk. PMID- 17731232 TI - Disease clue to dawn of agriculture. PMID- 17731234 TI - AAAS Socio-Psychological Prize. PMID- 17731233 TI - Report of west african science association. PMID- 17731235 TI - Science celebrates 100th anniversary. PMID- 17731236 TI - Obituaries. PMID- 17731237 TI - Hopeful efforts. PMID- 17731238 TI - Early environmentalism. PMID- 17731240 TI - Double stars. PMID- 17731239 TI - Vulpes vulpes. PMID- 17731241 TI - Echolocation. PMID- 17731242 TI - Stress anomaly accompanying the 1979 lytle creek earthquake: implications for earthquake prediction. AB - An unusual stress transient was recorded 15 kilometers from the epicenter of the Lytle Creek earthquake in southern California. It was observed at the recording site as an increased shear stress parallel to the fault surface and with the proper sense of shear to have triggered the earthquake. The anomaly began 2 to 4 weeks before the earthquake and lasted for 3 months. PMID- 17731243 TI - Siliceous microfossils from the lower cambrian of northwest Canada: possible source for biogenic chert. AB - Round to oval, scalelike siliceous microstructures from cherts in Cambrian limestones of the western Yukon Territory suggest affinity with chrysophycean algae. At least six morphotypes present include porous forms with single branching processes and nonporous oval, ringlike forms. Partially dissolved specimens may indicate a contribution to contemporaneous or early diagenetic chert formation. PMID- 17731244 TI - Strain on the san andreas fault near palmdale, california: rapid, aseismic change. AB - Frequently repeated strain measurements near Palmdale, California, during the period from 1971 through 1980 indicate that, in addition to a uniform accumulation of right-lateral shear strain (engineering shear, 0.35 microradian per year) across the San Andreas fault, a 1-microstrain contraction perpendicular to the fault that accumulated gradually during the interval 1974 through 1978 was aseismically released between February and November 1979. Subsequently (November 1979 to March 1980), about half of the contraction was recovered. This sequence of strain changes can be explained in terms of south-southwestward migration of a slip event consisting of the south-southwestward movement of the upper crust on a horizontal detachment surface at a depth of 10 to 30 kilometers. The large strain change in 1979 corresponds to the passage of the slip event beneath the San Andreas fault. PMID- 17731245 TI - Cellulose metabolism by the flagellate trichonympha from a termite is independent of endosymbiotic bacteria. AB - Continuous axenic cultures were established of Trichonympha sphaerica, a cellulose-digesting symbiotic protozoon in the gut of a termite. The cultured flagellates harbored no endosymbiotic bacteria and metabolized cellulose to acetate, carbon dioxide, and hydrogen. Thus, the cellulolytic activity of this flagellate is an inherent property and is not dependent on endosymbiotic bacteria. PMID- 17731247 TI - Invading the unknown. PMID- 17731246 TI - Thermoregulatory significance of thoracic lobes in the evolution of insect wings. AB - The evolution of broadly attached thoracic lobes could have increased the body temperature excess of ancient wingless insects by 55 percent over that of lobeless forms. The subsequent expansion of these thoracic lobes for behavioral thermoregulation could have provided the morphological stage required for the evolution of functional wings. PMID- 17731248 TI - Women in the job market. PMID- 17731249 TI - Plastic sandbags. PMID- 17731250 TI - PCB's in Microscope Immersion Oil. PMID- 17731251 TI - PCB Formation. PMID- 17731252 TI - Scientist in the senate. PMID- 17731253 TI - Correct formulas. PMID- 17731254 TI - Malignant tumors in monkeys. PMID- 17731255 TI - Agriculture, research, and shortages of funds and food. PMID- 17731257 TI - Medical evaluation: design for a comprehensive system. PMID- 17731256 TI - Thermal conductivities of the elements. PMID- 17731258 TI - Law of the sea meeting: a wet blanket for ocean research. PMID- 17731260 TI - A union for industrial scientists? PMID- 17731259 TI - Yale, too, reverses policy. PMID- 17731261 TI - Environmental precedent for nixon tapes case. PMID- 17731262 TI - Thin film optics: still in the exploratory stage. PMID- 17731263 TI - Gravitational Evidence for a Low-Density Mass beneath the Galapagos Islands. AB - A residual negative free-air and Bouguer anomaly of at least 80 milligals, superimposed on a broader high, occurs over the Galapagos Islands The axis of the anomaly trends roughly east and plunges eastward. Thus, a low-density mass in the crust or upper mantle must underlie the archipelago. This anomaly may be caused by thermal expansion over a crust-mantle " hot spot". PMID- 17731264 TI - Redistribution of Snowfall across a Mountain Range by Artificial Seeding: A Case Study. AB - Clouds over the western slopes of the Cascade Mountains were artificially seeded to reduce the riming and fall speeds of snow crystals and to divert snowfall across the crest. Aircraft observations showed that the clouds were glaciated by the seeding. The crystal habits and the degrees of riming of snow crystals reaching the target area were modified. Snowfall rates decreased at the crest and simultaneously increased 20 kilometers east of the crest. PMID- 17731265 TI - Climatic change on Mars. AB - The equatorial sinuous channels on Mars detected by Mariner 9 point to a past epoch of higher pressures and abundant liquid water. Advective instability of the martian atmosphere permits two stable climates-one close to present conditions, the other at a pressure of the order of 1 bar depending on the quantity of buried volatiles. Variations in the obliquity of Mars, the luminosity of the sun, and the albedo of the polar caps each appear capable of driving the instability between a current ice age and more clement conditions. Obliquity driving alone implies that epochs of much higher and of much lower pressure must have characterized martian history. Climatic change on Mars may have important meteorological, geological, and biological implications. PMID- 17731266 TI - Montmorillonite: electron-optical observations. AB - Fine-grained micas are consistent impurities in Camp-Berteaux (Morocco) and Wyoming montmorillonities. These micas give selected-area electron diffraction spot patterns with triclinic, monoclinic, and hexagonal symmetries similar tO those reported previously for monmorillonites. Camp-Berteaux montmorillonite appears as folded and flexible polycrystalline aggregates with pronounced texturing along the [02],[11], and[1i] directions. Wyoming montmorillonite displays better crystallinity and larger crystallite size, and its structure is no longer truly "turbostratic". PMID- 17731267 TI - Deep-sea species diversity: decreased gastropod diversity at abyssal depths. AB - Gastropod species diversity is low on the continental shelf, high on the continental slope and abyssal rise, and then decreases with increasing distance out onto the abyssal plain. Increased diversity below the continental shelf has been attributed to increased environmental stability. Decreased diversity on the abyss may result from extremely low productivity. PMID- 17731268 TI - Thermophilic ostracod: aquatic metazoan with the highest known temperature tolerance. AB - The upper lethal temperature for an ostracod of the genus Potamocypris collected from a thermal stream ranged from 49 degrees C for incubation of more than 5 hours to 55.75 degrees C for 1-minute incubations. Field collections were held at 35 degrees C for less than 24 hours before experimental incubations. Calculated temperatues for 50 percent mortality for 60, 40, 20, 10, 5, and 1 minute of exposure were 50.44 degrees , 50.96 degrees , 51.43 degrees , 52.03 degrees , 52.77 degrees , and 55.12 degrees C, respectively. PMID- 17731269 TI - Kinetosomes in insect epidermal cells and their orientation with respect to cell symmetry and intercellular patterning. AB - Paired flagellar basal bodies or kitnetosomles are described for tarsal, pulvillar, wing, proboscis, ptilinum, and tracheal epithelial cells in the fly Sarcophaga bullata. Evidence suggests that in every diploid epidermal cell their orientation is specific with respect to (i) cell symmetry and cuticular patterning, and (ii) intercellular positioninig and polarity. Microtrichia may be homologous with the flagella of other organisms. PMID- 17731270 TI - Hurricane seeding analysis. PMID- 17731271 TI - Stable limit cycles in prey-predator populations. PMID- 17731273 TI - Microdensitometer. PMID- 17731272 TI - Hormonal regulation of plant growth and morphogenesis. PMID- 17731274 TI - Gamma counters. PMID- 17731275 TI - Precision syringe. PMID- 17731276 TI - Automatic all-glass still. PMID- 17731278 TI - Automatic thermal value determinator. PMID- 17731277 TI - Controlled temperature optical bench. PMID- 17731280 TI - Literature. PMID- 17731279 TI - Heavy metal analysis. PMID- 17731281 TI - Recording osmometer. PMID- 17731282 TI - How To Be Generous Cheaply. PMID- 17731283 TI - Government Sponsorship of Scientific Research: A cabinet-level department of science could serve to develop support for neglected areas of research. PMID- 17731284 TI - Role of the Biological Station: It can bring field problems into the laboratory and test laboratory problems in the field. PMID- 17731285 TI - News of Science: Where Is Peking Man? Anthropologists Are Still Speculating about the War-Lost Specimens. PMID- 17731286 TI - Seasonal Growth Periodicity of Tissue Explants from Woody Perennial Plants in vitro. AB - Secondary phloem explants removed to standard aseptic culture in the spring proliferate most extensively. Explants taken successively through the growing season proliferate less. The decreasomg growth trend reverses some months before bud break, and the increasing growth in winter is not dependent on the breaking of dormancy in the terminal buds. PMID- 17731287 TI - Parthenogenesis in Culex fatigans. AB - Parthenogenesis occurs in the mosquito Culex fatigans. Three larvae were hatched from 85,851 eggs in tests of eggs from 1001 females. There were 618 egg rafts; the three larvae were from different rafts. PMID- 17731288 TI - Function of Giant Mauthner's Neurons in the Lungfish. AB - Unit spikes were recorded from the spinal cord of the lungfish Protopterus and were identified with Mauthner's axon. With these spikes occurred nongraded tail flips suggesting startle responses. The tail flip and the giant spike resulted from certain forms of jarring and prodding. The conduction velocity for the slightly myelinated. 45 micro diameter fibers was 18.5 m/sec. PMID- 17731290 TI - Equipment. PMID- 17731291 TI - Beneficiation of Soils Contaminated by Strontium-90. PMID- 17731292 TI - Nuclear Tests. PMID- 17731293 TI - Beneficiation of Soils Contaminated by Strontium-90. PMID- 17731294 TI - Beneficiation of Soils Contaminated by Strontium-90. PMID- 17731295 TI - Letter to the editor. PMID- 17731296 TI - Letter to the editor. PMID- 17731297 TI - Letter to the editor. PMID- 17731298 TI - Letter to the editor. PMID- 17731300 TI - Letter to the editor. PMID- 17731299 TI - Vigor of northern hardwoods. PMID- 17731301 TI - "Pieces of the action". PMID- 17731302 TI - Underground power transmission. AB - Much of the generating capacity to meet the needs of the future may be from generating stations in groups of two or three, each of 1000 Mw, located away from the growing urban areas. Transmission systems will become longer and be of higher duty; and a combination of popular demand and land cost will force the system underground at increasing distances from cities. The need for higher capacity cables to match the new overhead systems and for reduced capital and installation costs is forcing the search for better materials and new techniques. The vast size of the power industry implies that a breakthrough in technology would have dramatic consequences and even a small improvement in materials or techniques can be of significant economic importance. PMID- 17731303 TI - Semiconductor Radiation Detectors: Basic principles and some uses of a recent tool that has revolutionized nuclear physics are described. AB - The past decade has seen the rapid development and exploitation of one of the most significant tools of nuclear physics, the semiconductor radiation detector. Applications of the device to the analysis of materials promises to be one of the major contributions of nuclear research to technology, and may even assist in some aspects of our environmental problems. In parallel with the development of these applications, further developments in detectors for nuclear research are taking place: the use of very thin detectors for heavyion identification, position-sensitive detectors for nuclear-reaction studies, and very pure germanium for making more satisfactory detectors for many applications suggest major future contributions to physics. PMID- 17731305 TI - Faculty salaries: 1969-70 year may have ended an era for academe. PMID- 17731304 TI - Earth Strain Measurements with a Laser Interferometer: An 800-meter Michelson interferometer monitors the earth's strain field on the surface of the ground. AB - The development of the laser as a source of coherent optical radiation has permitted the application of interferometric techniques to the problem of earth strain measurement. By use of this technology, an 800-meter laser strain meter has been developed which operates above the surface of the ground. The instrument has a strain least count of 10(-10), requires no calibration, and has a flat and linear response from zero frequency to 1 megahertz. The linearity and large dynamic range of the laser strain meter offer unprecedented versatility in the recording of seismic strains associated with earthquakes and nuclear blasts. The extremely wide bandwidth opens new areas of the strain spectrum to investigation. A key to the understanding of the state of stress of the earth and the association phenomona of tectonic activity and earthquakes is a knowledge of the spatial distribution of the earth strain. Measurements of secular strain and earth tides indicate that, even at these long periods, surface strain measurements are valid representations of earth strain at depth. The LSM thus provides a means of making crustal strain measurements at points selected for maximum geophysical interest and ultimately allow the mapping of strain field distributions. PMID- 17731306 TI - Bureau of mines: long search for new director ends. PMID- 17731307 TI - Apospory in Sorghum bicolor (L.) Moench. AB - A line of Sorghum bicolor (L.) Moench was discovered to reproduce by apospory, a type of apomixis. The formation of an embryo by a nucellar cell without fertilization was establshed by cytological observations of ovaries and by progeny tests. PMID- 17731308 TI - Genetic diseases and the quality of life. PMID- 17731309 TI - THE ASTRONOMICAL AND ASTROPHYSICAL SOCIETY OF AMERICA. PMID- 17731310 TI - THE ASSOCIATION OF AMERICAN ANATOMISTS. PMID- 17731311 TI - THE ASSOCIATION OF ECONOMIC ENTOMOLOGISTS. PMID- 17731312 TI - THE BOTANICAL SOCIETY OF AMERICA. PMID- 17731314 TI - SIGNS OF THE GLACIAL PERIOD IN JAPAN. PMID- 17731313 TI - ELECTION OF FELLOWS. PMID- 17731315 TI - MOUNTAIN SPECTRE NEAR BOULDER, COLORADO. PMID- 17731317 TI - TYPES OF PRE-LINNAeAN GENERA. PMID- 17731318 TI - A GRANT FROM THE CARNEGIE INSTITUTION FOR PALEOBOTANY. PMID- 17731316 TI - THE FALL OF BODIES. PMID- 17731319 TI - Current Notes on Meteorology. PMID- 17731320 TI - ABANDONED CHANNELS OF THE MONONGAHELA. PMID- 17731321 TI - AGE OF THE TYPICAL JUDITH RIVER BEDS. PMID- 17731322 TI - A NEW DIVISION OF THE UNITED STATES GEOLOGICAL SURVEY. PMID- 17731323 TI - SCIENCE NEWS. PMID- 17731324 TI - THE GERMINAL BACKGROUND OF SOMATIC MODIFICATIONS. PMID- 17731325 TI - THE NATIONAL ARBORETUM. PMID- 17731326 TI - BACTERIUM GRANULOSIS AND TRACHOMA. PMID- 17731328 TI - THE PASSENGER PIGEON. PMID- 17731327 TI - SEVERE HAIL INJURY TO TREES AND SHRUBS. PMID- 17731329 TI - MAN-MADE EARTHQUAKES. PMID- 17731330 TI - IN AID OF AMERICAN MEDICAL BIOGRAPHY. PMID- 17731331 TI - THE CANCER RESEARCH FUND OF THE UNIVERSITY OF PENNSYLVANIA. PMID- 17731332 TI - A DIET FOR STOCK RATS. PMID- 17731333 TI - AN IMPROVED CALOMEL ELECTRODE VESSEL. PMID- 17731334 TI - OCEANOGRAPHIC INVESTIGATIONS IN THE INSHORE WATERS OF THE GULF OF MAINE. PMID- 17731335 TI - THE RELATION OF THE OXYGEN TENSION IN THE EXTERNAL RESPIRATORY MEDIUM TO THE OXYGEN CONSUMPTION OF FISHES. PMID- 17731337 TI - A SYSTEM OF ORTHOGRAPHY FOR NATIVE NAMES OF PLACES. PMID- 17731336 TI - HEALTH MATTERS. PMID- 17731339 TI - BASCOM'S SOCIOLOGY. PMID- 17731338 TI - PSYCHIC BLINDNESS. PMID- 17731340 TI - JUKES-BROWNE'S HISTORICAL GEOLOGY. PMID- 17731341 TI - A CENTURY OF ELECTRICITY. PMID- 17731342 TI - BERGHAUS'S ATLAS OF PHYSICAL GEOGRAPHY. PMID- 17731343 TI - Letter to the editor. PMID- 17731344 TI - Military research and development. PMID- 17731345 TI - Stimulating blood donation. PMID- 17731347 TI - Apology to rhine and soal. PMID- 17731348 TI - Letter to the editor. PMID- 17731346 TI - National register. PMID- 17731349 TI - NSF: A Look Ahead. PMID- 17731350 TI - The apollo 15 lunar samples: a preliminary description. AB - Samples returned from the Apollo 15 site consist of mare basalts and breccias with a variety of premare igneous rocks. The mare basalts are from at least two different lava flows. The bulk chemical compositions and textures of these rocks confirm the previous conclusion that the lunar maria consist of a series of extrusive volcanic rocks that are rich in iron and poor in sodium. The breccias contain abundant clasts of anorthositic fragments along with clasts of basaltic rocks much richer in plagioclase than the mare basalts. These two rock types also occur as common components in soil samples from this site. The rocks and soils from both the front and mare region exhibit a variety of shock characteristics that can best be ascribed to ray material from the craters Aristillus or Autolycus. PMID- 17731351 TI - Genes conferring specific plant disease resistance. AB - Genes conferring host resistance to an obligate parasite, grouped together in complex loci provide opportunities to study their structure. By means of an appropriate operational definition of these genes, a modified cis-trans test was used to interpret the position effects of codominant genes mutually recombined within each of two complex loci of flax, with the use of a specially developed method of analysis among F(2) segregants. The different behavior of genes in the M and L groups may reflect a difference in their structure sufficient to raise important implications in the theory of specific host-parasite interactions. PMID- 17731353 TI - 1973 budget: administration bets on applied science. PMID- 17731352 TI - Weight-watching at the university: the consequences of growth. AB - We began by pointing out that tools (for example) have size optima that are dictated by function. If we assume that the university has a function, it would seem reasonable to think about the size which will serve that function best. The principle of size optimization is fundamental, but its application to the university at once encounters a difficulty: What is the function of a university? It might take forever to secure general agreement on the answer to this question. The problem is that universities have a number of different functions, to which different individuals will attach different weights, and each function may well have a unique size optimum. Just as it is, in general, mathematically impossible to maximize simultaneously for two different functions of the same variable (29), so it is unsound to conceive of a single optimum for the multiversity. Nonetheless, a range of workable sizes may be defined by analyzing the effect of variation in size on all essential functions. The examples from biological systems illustrate this approach. Cells exist in a variety of sizes, each size presumably representing an optimization to one or another set of constraints, yet there are upper bounds. There are no cells the size of basketballs because essential metabolic functions are limited by the surface-to-volume ratio. We must emphasize that one does not need a grand theory of life in order to identify this limiting condition. If cells could talk, they would no doubt differ on the general philosophy of being a cell, yet all conceptions would be subject to certain physically inevitable limitations on size. In the case of the university, no grand theory of education is needed in order to identify dysfunctions of growth that affect essential activities (for example, the diffusion of individuals through, in, and out of the university) or that affect all activities (for example, overall morale). Balanced against these dysfunctions are such advantages of growth as economy, the achievement of a critical mass, and flexibility in staffing. Our analyis of data from the California system indicates that unit costs of education decline very little above a size of 10,000 or 15,000 students. Moreover, the critical mass for departmental excellence, at least in terms of the ACE ratings of graduate departments, is achieved by a university of about this size. Growth beyond this size range conitinues to provide flexibility in staffing and spares administrators the trouble of having to make difficult decisions. At the same time, the dysfunctions attendant on growth become steadily more severe. Our impression is that the dysfunctions have not been seriously considered, while the advantages have been greatly oversold. The idea of dysfunctional growth, although fundamental in biology, contradicts one of America's most cherished illusions. Particular dysfunctions of growth are rarely formulated, set down, and explicitly weighed against the potential advantages. Rather, the American prejudice has been to assume that growth is always good, or at least inevitable, and to treat the dysfunctions (which are inevitable) as managerial problems to be ironed out later or glossed over. There has also been a remarkable failure to think in terms of optima and to distinguish in this way between what we have termed functional and dysfunctional growth. Rather, the tendency has been to extrapolate functional growth into the dysfunctional range: If a university population of 10,000 confers certain advantages as compared with a population of 1,000, then it is assumed that a population of 100,000 must confer even more advantages. We suggest that it is time, in fact past time, to subject university growth to a more searching scrutiny. Functional and dysfunctional consequences need to be spelled out. Scale effects ought to be considered in connection with every plan for expansion. Ideally, one might expect a farsighted and tough-minded administration to carry out this function. This has rarely been the case. Too often administrators regard their function as simply that of broker among competing expansionist tendencies. Such a conception replaces philosophy by politics and often encourages mindless growth. Perhaps it is time for faculties to involve themselves in long-range planning and to pay the price of a more satisfactory environment by giving up some individual dreams of empire. The first step for every large university ought to be a careful analysis of scale effects (30). If analysis indicates that continued growth of a university will be, on balance, dysfunctional, we suggest that plans be formulated to establish an absolute limit on further enrollment increase, and an absolute limit on further building expansion. If further analysis indicates that a university is already well into the dysfunctional size range, then the obvious solution is to cut back. If this turns out to be the case, then we suggest that a program for the gradual reduction of the campus population be undertaken. There are two distinct ways to accomplish this: (i) the establishment of a new university and (ii) the decentralization of the existing university into two or more campuses. Decentralization strikes us as an attractive idea, worthy of careful study. One of the recommendations of the Scranton commission was, "Large universities should take steps to decentralize or reorganize to make possible a more human scale" (18, p. 14). Returning to the natural world, we note again that cells do not grow indefinitely. Instead, they divide. PMID- 17731355 TI - Space shuttle: compromise version still faces opposition. PMID- 17731354 TI - NSF: A Boost for Relevance. PMID- 17731356 TI - Environmental action organizations are suffering from money shortages, slump in public commitment. PMID- 17731357 TI - X-ray Astronomy: Observations of New Phenomena. PMID- 17731358 TI - Geologic setting of the apollo 15 samples. AB - The samples and photographs returned from the Apollo 15 site show that Hadley Delta is largely underlain by breccias whose clasts are mainly fragments of coarse-grained feldspathic rocks and nonmare-type basalt. Conspicuous sets of lineaments, visible in surface and orbital photographs of Mount Hadley and Hadley Delta, may represent systematic layering or fracture sets. The mare surface, with regolith about 5 meters thick, is underlain by two major basalt types, at least one of which has extensive lateral continuity and is exposed in the upper wall of Hadley Rille. Gradual erosional recession of the edges and filing of the interior of the rille by talus have contributed to the present cross sectional profile. PMID- 17731359 TI - Chemistry, geochronology, and petrogenesis of lunar sample 15555. AB - Lunar sample 15555 is a mare type basalt generally similar in chemical composition to the Apollo 12 basalts. Sample 15555 is older than any Apollo 12 basalt but younger than the Apollo 14 basalts analyzed thus far. PMID- 17731360 TI - Argon-40-argon-39 dating of apollo sample 15555. AB - An age of 3.33+/-0.05x10(9) years was obtained for Apollo 15 sample 15555 by argon40-argon-39 dating. The age of rock 15555, a basalt from the rim of Hadley Rille, establishes an upper limit to the age of the rille. The basalt flows filling the Hadley Rille section of the Imbrium basin postdate the formation of the basin-as measured by the Apollo 14 samples of the Fra Mauro formation-by at least 500x10(6) years. Therefore, the mare basalts cannot be simple impact melts but rather must result from some igneous activity on the moon. PMID- 17731361 TI - Rubidium-strontium and potassium-argon age of lunar sample 15555. AB - The lunar mare basalt 15555 from the edge of Hadley Rille has been dated at 3.3x10(9) years by both rubidium-strontium and potassium-argon techniques. Age and trace element abundances closely resemble those of the Apollo 12 mare basalts. Data from lunar basalts obtained thus far indicate that they cannot be derived by simple fractionation from a homogeneous source. PMID- 17731362 TI - Rare gas record in the largest apollo 15 rock. AB - The spallation krypton data from rock chip 15555,23 indicate a wellshielded location during most of the time during which the rock was exposed to cosmic rays. A krypton-krypton exposure age of 81(+17)(-7) x 10(6) years is calculated, and the gas retention ages are estimated. No evidence for the presence of products from plutonium-244 or iodine-129 was found. PMID- 17731363 TI - Gas-retention and cosmic-ray exposure ages of lunar rock 15555. AB - The last lava flow in the Hadley Rille area of Mare Imbrium, as inferred from an argon-40-argon-39 experiment on a plagioclase separate from the lunar basalt 15555, occurred 3.31+/-0.03x10(9) years ago. An argon-40-argon-39 experiment on a whole rock sample shows significant loss of radiogenic argon-40 and yields a well defined, high-temperature plateau indicating a lower age of 3.22+/-0.03x10(9) years. A cosmic-ray exposure age of 90+/-10x10(6) years is determined from the ratio of spallogenic argon-38 to calcium. PMID- 17731364 TI - Geochemistry of apollo 15 basalt 15555 and soil 15531. AB - Major and trace element concentrations have been determined by atomic absorption spectrophotometry, colorimetry, and isotope dilution in Apollo 15 mare basalt 15555 from the Hadley Rille area; trace element concentrations have also been determined in plagioclase and pyroxene separates from basalt 15555 and in soil 15531 from the same area. Basalt 15555 most closely resembles in composition the Apollo 12 olivine-rich basalts. The concentrations of lithium, potassium, rubidium, barium, rare-earth elements, and zirconium in basalt 15555 are the lowest, and the negative europium anomaly is the smallest, reported for lunar basalts; this basalt might be the least differentiated material yet returned from the moon. Crystallization and removal of about 6 percent of plagioclase similar to that contained in the basalt would account for the observed europium anomaly; if plagioclase is not on the liquidus of this basalt, a multistage origin is indicated. Mineral data indicate that plagioclase and pyroxene approached quasi equilibrium. Most of the chemical differences between basalt 15555 and soil 15531 would be accounted for if the soil were a mixture of 88 percent basalt, 6 percent KREEP (a component, identified in other Apollo soils, rich in potassium, rare earth elements, and phosphorus) and 6 percent plagioclase (anorthosite?). PMID- 17731365 TI - Age of a lunar anorthosite. AB - The crystallization age of an Apollo 15 anorthosite rock, 15415,9, returned from the lunar highlands has been measured to be (4.09 +/- 0.19) x 10(9) years. The primitive lunar crust must have been formed in the first 300 to 400 x 10(6) years. The results give some credence to the hypothesis that the primitive lunar surface was molten and large-scale fractional crystallization occurred in the early history of the moon. PMID- 17731366 TI - Mineralogic and petrologic study of lunar anorthosite slide 15415,18. AB - The anorthosite slide 15415,18 contains 98 percent subhedral plagioclase (97 mole percent anorthite), two pyroxenes: diopsidic augite (46 percent wollastonite, 39 percent enstatite, 16 percent ferrosilite) with subsidiary (100) lamellae and grains of hypersthene (2.5 percent wollastonite, 58 percent enstatite, 39.5 percent ferrosilite), and traces of ilmenite. The pyroxene occurs interstitial to, and as small grains enclosed within, plagioclase. The textures and compositions of the phases appear compatible with an origin by concentration and adcumulus growth of plagioclase from a gabbroic anorthosite (or hyperaluminous) magma in a "plutonic" environment. PMID- 17731367 TI - Lunar anorthosite 15415: texture, mineralogy, and metamorphic history. AB - Lunar anorthosite 15415 consists almost entirely of anorthite (homogeneous anorthite 96.6 molecule percent), with accessory diopsidic augite and traces of hypersthene, ilmenite, and a silica mineral. The rock has had a complex metamorphic history. The texture reflects at least two episodes of shearing (followed by intense and partial recrystallization, respectively), one episode of cataclastic deformation, and one or more episodes of shattering and fragmentation. PMID- 17731368 TI - Apollo 15 Geochemical X-ray Fluorescence Experiment: Preliminary Report. AB - Although only part of the information from the x-ray fluorescence geochemical experiment has been analyzed, it is clear that the experiment was highly successful. Significant compositional differences among and possibly within the maria and highlands have been detected. When viewed in the light of analyzed lunar rocks and soil samples, and the data from other lunar orbital experiments (in particular, the Apollo 15 gamma-ray spectroscopy experiment), the results indicate the existence of a differential lunar highland crust, probably feldspathic. This crust appears to be related to the plagioclase-rich materials previously found in the samples from Apollo 11, Apollo 12, Apollo 14, Apollo 15, and Luna 16. PMID- 17731369 TI - Primordial radioelements and cosmogenic radionuclides in lunar samples from apollo 15. AB - Two basalts, two breccias, and two soils from Apollo 15 were analyzed by nondestructive gamma-ray spectrometry. The concentrations of potassium, thorium, and uranium in the basalts were similar to those in the Apollo 12 basalts, but the potassium: uranium ratios were somewhat higher. Primordial radioelements were enriched in the soils and breccia, consistent with a two-component mixture of mare basalt and up to 20 percent foreign component (KREEP). The abundance patterns for cosmogenic radionuclides implied surface sampling for all specimens. The galactic cosmic-ray production rate of vanadium-48 was determined as 57 +/- 11 disintegrations per minute per kilogram of iron. Cobalt-56 concentrations were used to estimate the intensity of the solar flare of 25 January 1971. PMID- 17731371 TI - Long-term habituation of a defensive withdrawal reflex in aplysia. AB - A tactile stimulus to the siphon of Aplysia produces a defensive withdrawal reflex consisting of contraction of the siphon, the gill, and the mantle shelf. We studied long-term habituation of this reflex using two types of preparations, one focusing on the siphon component and the other on the gill component of the reflex. Siphon withdrawal, studied in unrestrained animals, showed marked habituation within a single ten-trial training session. Five daily training sessions produced habituaton that built up across days and lasted for at least 3 weeks. Furthermore, spaced training produced significantly longer lasting habituation than massed training. Gill withdrawal, studied in a restrained animal, also showed long-term retention of habituation. Since the neural circuitry of gill withdrawal is relatively well understood, it may be possible to study the cellular mechanisms underlying a long-term behavioral modification. PMID- 17731370 TI - Mars: an evolving atmosphere. AB - Photochemical reactions in the martian exosphere produce fast atoms of oxygen, carbon, and nitrogen and provide large escape fluxes of these elements. They appear to play a crucial role in the evolution of the martian atmosphere. The relative outgassing rates of H(2)O and CO(2) on Mars are comparable with terrestrial values, although absolute rates for Mars are lower by a factor of 10(3). Nitrogen is a trace constituent, less than 1 percent, of the present martian atmosphere. PMID- 17731372 TI - Patent System. PMID- 17731374 TI - Two Cheers for West Ford. PMID- 17731373 TI - Econology and Word Coinage. PMID- 17731375 TI - Optical Rotatory Dispersion: Investigation of the phenomenon 140 years after its discovery sheds light on problems of organic chemistry. PMID- 17731376 TI - End of the Test Ban: The White House Response Is Restrained; Educational TV in Court. PMID- 17731377 TI - Influence of Soil Oxygen Concentrations on the Development of Meloidogyne javanica. AB - Roots of tomato plants infected with Meloidogyne javanica were grown in soil subjected to oxygen concentrations of 21 percent, 5.5 percent, 3.5 percent, 2.0 percent, 0.6 percent, and 0 percent for 28 and 35 days. The lowest oxygen tension which still allowed development of the host and the nematode was 3.5 percent. Below this level the plant root growth, size of developing females, and production of nematode eggs were reduced. Nematode activity as measured bythe number of nematode galls on the roots of treated plants was sharply reduced at the 5.5-percent level of oxygen. PMID- 17731378 TI - Stimulation of Uterine Contraction by Extracts of the Cockroach, Periplaneta. AB - Blood and extracts of gut of the American cockroach, Periplaneta americana, powerfully stimulate contractions of the isolated rat uterus. The contractions are characterized by long latency and a prolonged relaxation phase having superimposed rhythmic contractions. Evidence indicates that the stimulating factor is not acetylcholine, 5-hydroxytryptamine, histamine, or substance P. The active factor is heat labile and nondialyzable. PMID- 17731379 TI - Succession in Desert Vegetation on Streets of a Nevada Ghost Town. AB - Vegetation was sampled on the old street system of Wahmonie, Nevada, and on a less disturbed area immediately adjacent. The vegetation on the denuded upland site showed a large increase in bunch-grass and an invasion by pioneer shrubs which ordinarily are chiefly confined to dry washes. PMID- 17731380 TI - Biosynthesis of Stigmasterol in Tomato Fruits. AB - The presence of stigmasterol in tomato fruits was demonstrated. Labeled mevalonic acid was incorporated into this sterol, while sodium acetate was not. The identity of the isolated product was established by rigorous purification to constant specific activity, melting point determinations, and infrared spectrum. PMID- 17731381 TI - Chemical Analysis of Surfaces by Use of Large-Angle Scattering of Heavy Charged Particles. AB - The Rutherford scattering of carged particles from the heavier elements and nuclear scattering and (alpha,p) reactions from the light elements result in energy spectra that are characteristic of the nucleus being bombarded. A simple apparatus for analyzing surfaces based on these ideas can be made by using an alpha source such as Cm244, a solid state detector, and an electronic pulse height analyzer. PMID- 17731382 TI - General Method of Plotting Kinetic Data for Reactions of Any Order. AB - A method is presented for obtaining from kinetic experiments both order of reaction and rate constant by means of a single straight-line graph, in contrast to previous methods, which require several steps including more than one graph or repeated trial-and-error calculations whenever there is no prior knowldege of the order of reaction. PMID- 17731383 TI - Carbon Conference. PMID- 17731384 TI - Forthcoming Events. PMID- 17731385 TI - CONTRIBUTIONS OF PHARMACOLOGY TO PHYSIOLOGY. PMID- 17731386 TI - THE GEOGRAPHICAL DISTRIBUTION OF THE STUDENT BODY AT A NUMBER OF AMERICAN UNIVERSITIES. PMID- 17731388 TI - THE PROBABLE ORIGIN OF CERTAIN BIRDS. PMID- 17731387 TI - AMERICAN MATHEMATICAL SOCIETY. PMID- 17731389 TI - BATTERY RESISTANCE BY MANCE'S METHOD. PMID- 17731390 TI - ORGANISMS ON THE SURFACE OF GRAIN, WITH SPECIAL REFERENCE TO BACILLUS COLI. PMID- 17731391 TI - THE INTERNATIONAL CATALOGUE OF SCIENTIFIC LITERATURE. PMID- 17731392 TI - EXPERIMENTAL STUDIES IN YELLOW FEVER AND MALARIA AT VERA CRUZ. PMID- 17731394 TI - SURFACES OF SOLIDS IN SCIENCE AND INDUSTRY. PMID- 17731393 TI - INAUGURATION OF THE MAGNETIC SURVEY OF THE NORTH PACIFIC OCEAN. PMID- 17731395 TI - HAROLD HIBBERT. PMID- 17731397 TI - NEWS FROM ABROAD. PMID- 17731396 TI - NAVY HOSPITAL FOR ASTHMATICS AND ASSOCIATED ALLERGIES. PMID- 17731398 TI - THE HENRY NORRIS RUSSELL LECTURESHIP OF THE AMERICAN ASTRONOMICAL SOCIETY. PMID- 17731399 TI - A MANAGING COMMITTEE FOR THE WESTINGHOUSE SCIENCE WRITING AWARD. PMID- 17731401 TI - THE FREE TRYPTOPHANE CONTENT OF HUMAN URINE. AB - The amount of 1-tryptophane excreted per day by 9 different normal male subjects was determined by a microbiological method with L. arabinosus as the test organism. From 12-30 mg per day were excreted as contrasted to an average value of 281 mg per day reported by Albanese and Frankston. A negligible amount of indole in the urine could be demonstrated. Satisfactory values and recoveries of 1-tryptophane were obtained at different levels of the test sample. PMID- 17731400 TI - MODIFICATION OF GRAMICIDIN THROUGH REACTION WITH FORMALDEHYDE. PMID- 17731402 TI - THE ELECTRON MICROGRAPHY OF CRYSTALLINE PLANT VIRUSES. PMID- 17731403 TI - THE MEASUREMENT OF BLOOD OXYGEN IN MALARIA WITH THE USE OF THE OXIMETER. PMID- 17731405 TI - PRECIPITABLE TYPHOID SOMATIC ANTIGEN IN THE SERUM OF TYPHOID FEVER PATIENTS. PMID- 17731404 TI - THE RELATION OF HYPERSENSITIVENESS TO POISON IVY AND TO CASHEW NUT SHELL LIQUID. PMID- 17731406 TI - RESEARCH. PMID- 17731407 TI - REMOVING THE SHELL FROM LIVING GRASSHOPPER EGGS. PMID- 17731409 TI - WEAR IN ENGINE CYLINDERS. PMID- 17731408 TI - THE PROGRESS OF SOVIET PALEOBOTANY. PMID- 17731410 TI - ANOTHER VALUE OF A NATIONAL POLICY OF RESEARCH. PMID- 17731411 TI - SOME PROBLEMS IN INFECTION AND ITS CONTROL. PMID- 17731412 TI - FACULTY PARTICIPATION IN UNIVERSITY GOVERNMENT. PMID- 17731413 TI - THE CLEVELAND CONVOCATION WEEK MEETING. PMID- 17731414 TI - A SIMPLE DEMONSTRATION OF THE ACTION OF NATURAL SELECTION. PMID- 17731415 TI - THE DOMAIN OF COMPUTATIONAL ASTRONOMY. PMID- 17731416 TI - SPECIAL ARTICLES. PMID- 17731417 TI - THE PROBABLE RECENT EXTINCTION OF THE MUSKOX IN ALASKA. PMID- 17731418 TI - THE NATIONAL ACADEMY OF SCIENCES. PMID- 17731420 TI - W. Kaempffert, Science Popularizer. PMID- 17731419 TI - Radiation and Health. PMID- 17731421 TI - News of Science. PMID- 17731422 TI - Induced Copulation of Aedine Mosquitoes. PMID- 17731424 TI - Meetings and Societies. PMID- 17731423 TI - National Academy of Sciences. PMID- 17731425 TI - EQUIPMENT NEWS. PMID- 17731426 TI - This week in science. PMID- 17731427 TI - High-tech materials processing. PMID- 17731428 TI - Erratum. AB - In the first paragaph on page 1005 of the article "A molecular basis for MHC class II-associated autoimmunity" by John A. Todd et al. (20 May, p. 1003), invention of the polymerase chain reaction amplification method was incorrectly attributed to "Erlich and colleagues." The method was invented by Kary Mullis at the Cetus Corporation and developed by Erlich's group. PMID- 17731429 TI - Nonprofits Could Face a Taxing Time: Ways and Means panel report recommends broad tax changes, including heavier levies on journal advertising revenue. PMID- 17731430 TI - NSF and Antarctic Wastes. PMID- 17731431 TI - Setting Research Goals Not Enough, Says OECD: Policies to encourage more research on topics of economic importance seem to be effective only in countries with relatively strong central control over allocation of resources. PMID- 17731432 TI - Solar Cells Turn 30: Photovoltaics have passed an important milestone with the development of the first solar cell to surpass 30% efficiency in converting sunlight to electricity. PMID- 17731434 TI - Heads Up! Sunspots Are Dragging Down Satellites: When solar activity surges toward a maximum, Earth satellites drift downward with potentially disastrous results. PMID- 17731433 TI - A bright sport on the solar scence. PMID- 17731435 TI - The Farthest Galaxies: A New Champion: A survey of high red shift radio galaxies, which are the first cousins of quasars, has uncovered a galaxy called 4C41.17 that is roughly 15 billion light years away. PMID- 17731436 TI - A Huge Problem for NIH? PMID- 17731437 TI - A bit of science history is lost. PMID- 17731438 TI - Things are popping at the academy. PMID- 17731439 TI - Low-pressure, metastable growth of diamond and "diamondlike" phases. AB - Diamond may be grown at low pressures where it is the metastable form of carbon. Recent advances in a wide variety of plasma and electrical discharge methods have led to dramatic increases in growth rates. All of these methods have certain aspects in common, namely, the presence of atomic hydrogen and the production of energetic carbon-containing fragments under conditions that support high mobilities on the diamond surface. Some understanding of the processes taking place during nucleation and growth of diamond has been achieved, but detailed molecular mechanisms are not yet known. Related research has led to the discovery of a new class of materials, the "diamondlike" phases. Vapor-grown diamond and diamondlike materials may have eventual applications in abrasives, tool coatings, bearing surfaces, electronics, optics, tribological surfaces, and corrosion protection. PMID- 17731440 TI - Processing Techniques for the 93 K Superconductor Ba2YCu3O7. AB - Superconductivity above the temperature of liquid nitrogen in copper oxide-based systems has led to optimism that superconductors may at last find wide application. The critical temperature, however, is just one of the required parameters. The materials must be made into usable forms such as wire, thick films, thin films, and bulk ceramics. In addition, the critical current in these various forms is a crucial test of their utility. This article reviews the processing techniques used to fabricate potentially useful forms and assesses remaining problems. Considerable improvement in critical current density is necessary in bulk materials, and thin films need to be made compatible with other thin-film technology. PMID- 17731441 TI - Synthesis of buried oxide and silicide layers with ion beams. AB - Ion implantation, because it is inherently a strongly nonequilibrium process, can add a new dimension to materials studies. A large variety of chemical elements may be readily introduced into a target substrate by ion bombardment at concentrations considerably greater than the normal solid solubilities. In addition, the interaction of the accelerated ions with the target produces lattice defects. Both effects have been studied extensively in experiments directed at understanding the mechanisms of formation of buried oxide and silicide layers in silicon with high-dose ion implantation. These layers have properties that are difficult to attain with conventional techniques. PMID- 17731442 TI - A new laboratory source of ozone and its potential atmospheric implications. AB - Although 248-nanometer radiation falls 0.12 electron volt short of the energy needed to dissociate O(2) large densities of ozone (O(3)) can be produced from unfocused 248-nanometer KrF excimer laser irradiation of pure O(2). The process is initiated in some undefined manner, possibly through weak two-photon O(2) dissociation, which results in a small amount of O(3) being generated. As soon as any O(3) is present, it strongly absorbs the 248-nanometer radiation and dissociates to vibrationally excited ground state O(2) (among other products), with a quantum yield of 0.1 to 0.15. During the laser pulse, a portion of these molecules absorb a photon and dissociate, which results in the production of three oxygen atoms for one O(3) molecule destroyed. Recombination then converts these atoms to O(3), and thus O(3) production in the system is autocatalytic. A deficiency exists in current models of O(3) photochemistry in the upper stratosphere and mesosphere, in that more O(3) iS found than can be explained. A detailed analysis of the system as it applies to the upper atmosphere is not yet possible, but with reasonable assumptions about O(2) vibrational distributions resulting from O(3) photodissociation and about relaxation rates of vibrationally excited O(2) a case can be made for the importance of incuding this mechanism in the models. PMID- 17731443 TI - Enhancement of symbiotic dinitrogen fixation by a toxin-releasing plant pathogen. AB - An approximate doubling in plant growth, total plant nitrogen, nodulation, and overall dinitrogen fixation of alfalfa are the consequences of the action of a toxin delivered by a Pseudomonas infesting the alfalfa rhizosphere. The toxin, tabtoxinine-beta-lactam, inactivates selectively one form of glutamine synthetase in the nodules. Thus, normal glutamine synthetase-catalyzed ammonia assimilation is significantly impaired; yet these plants assimilated about twice the normal amount of nitrogen. How plants regulate dinitrogen fixing symbiotic associations is an important and unresolved question; the current results imply that the glutamine synthetase-catalyzed step in ammonia assimilation, a plant function, strongly influences overall dinitrogen fixation in legumes. PMID- 17731444 TI - The incommensurate modulation of the 2212 bi-sr-ca-cu-o superconductor. AB - The incommensurate modulation evident in the diffraction pattern of the superconductor Bi(2)Sr3-xCa(x)Cu(2)O8+y consists of almost sinusoidally varying displacements of up to 0.4A of the Bi and Sr atoms in the a-and c-directions of the unit cell, and of up to 0.3 A of the Cu atoms in the c direction only. Thus, a newly discovered feature of the Bi(2)Sr3-xCaxCu(2)O8+y structure is sizable Cu displacement, which is related to static wave formation in the Cu-O sheets. Reported thermal parameters give evidence that similar distortions occur on cooling of the thallium-containing superconductors. PMID- 17731446 TI - 4th National AAAS Forum for School Science: Science Teaching Making the System Work. PMID- 17731445 TI - Neutron imaging of laser fusion targets. AB - Along-term goal of inertial-confinement fusion research is the generation of energy by imploding capsules containing deuterium-tritium fuel. Progress in designing the capsules is aided by accurate imaging of the fusion burn. Penumbral coded-aperture techniques have been used to obtain neutron images that are a direct measurement of the fusion burn region in the capsules. PMID- 17731447 TI - Nuclear-weapon decisions: nuclear non-proliferation. PMID- 17731448 TI - Academic trials: cold war on campus. PMID- 17731449 TI - Some other books of interest: neutral models in biology. PMID- 17731450 TI - Radon reduction: radon and its decay products in indoor air. PMID- 17731451 TI - Some other books of interest: ontogeny and systematics. PMID- 17731453 TI - THE ORIGIN OF THE VERTEBRATES. PMID- 17731452 TI - Products & materials. PMID- 17731455 TI - ULTRA-VIOLET RAYS AND RICKETS. PMID- 17731454 TI - THE ROCKS AND HILLS OF DAYTON TESTIFY FOR EVOLUTION. PMID- 17731456 TI - COLOR SIGNALS IN SWEDISH RAILWAY CROSSINGS. PMID- 17731457 TI - TRANSPLANTATION OF MALE SEX GLANDS. PMID- 17731458 TI - TRAINED MONKEYS. PMID- 17731459 TI - ETHER-DRIFT EXPERIMENTS AT MOUNT WILSON. PMID- 17731461 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17731460 TI - RISKS INCURRED IN THE INTRODUCTION OF ALIEN GAME BIRDS. PMID- 17731462 TI - THE REFORM OF THE CALENDAR. AB - Persons who are interested in an immediate reform of the calendar might well confine their efforts to a readjustment of the lengths of the months. A few minor changes would make possible simplifications of benefit to every one. Those making a study of perpetual calendars, expecting to eventually secure the adoption of one, should consider not only the "no-week" day, but also the "intercalary week." PMID- 17731464 TI - THE JONAS VILES, JR., MEMORIAL SCHOLARSHIP. PMID- 17731463 TI - BACTERIAL CATALASE. PMID- 17731465 TI - HEAVY MINERAL OIL AS A PERMANENT NON-VOLATILE PRESERVATIVE FOR VALUABLE BIOLOGICAL MATERIAL. PMID- 17731466 TI - ARC SPECTRUM REGULARITIES FOR RUTHENIUM. PMID- 17731467 TI - MANGANESE AS A CURE FOR A CHLOROSIS OF SPINACH. PMID- 17731468 TI - PHYSICAL AND INORGANIC CHEMISTRY. PMID- 17731470 TI - Racial differences: dilemma of college admissions. PMID- 17731469 TI - Our quality of life arouses student skeptics. PMID- 17731471 TI - Is the AAAS Council Facing Its Responsibilities? PMID- 17731473 TI - Apollo and post-apollo. PMID- 17731472 TI - NIH: Ethics of Budget Cutting and Retrenchment. PMID- 17731474 TI - Transversely aligned seismicity and concealed structure. PMID- 17731475 TI - Computer-assisted design of complex organic syntheses. PMID- 17731476 TI - The siege of the house of reason. PMID- 17731477 TI - Ernest j. Sternglass: controversial prophet of doom. PMID- 17731480 TI - Summary of the Academy Report: Effects of Three Jetport Developments are Analyzed. PMID- 17731478 TI - House threatens unrestful colleges. PMID- 17731481 TI - Everglades jetport: academy prepares a model. PMID- 17731482 TI - Oil in the ecosystem. PMID- 17731483 TI - Radioisotopes and the history of nucleosynthesis in the galaxy. AB - Nearly all of the heavier elements seem to have been assembled by successive neutron captures occurring in two distinct processes: the s (slow) process refers to neutron capture at a rate which is slow compared to the intervening beta decay; the r (rapid) process refers to neutron capture at a rate which is rapid compared to the beta process. It is becoming increasingly apparent that simple models for galactic r-process nucleosynthesis are inadequate. Modern astronomical observations, which indicate that the bulk of r-process synthesis may have occurred early in the life of the galaxy, cannot be ignored. Recent data on the fissiogenic xenon in whitlockite from the St. Severin meteorite also place stringent conditions on permissible models for element synthesis. It appears that neither sudden nor continuous models for element formation are consistent with isotopic data now available. I propose a more complex model for the synthesis of solar system material in which the r-process is allowed to occur in three distinct modes: a "prompt" synthesis early in the history of the galaxy, a "continuous" synthesis whereby r-process products are continuously added to the galactic mix, and a "last-minute" synthesis which enriches the solar nebula with r-process material shortly before the formation of the solar system. Calculations based on the present abundances of uranium-235, uranium-238, and thorium-232 and the measured abundances of iodine-129 and plutonium-244 present when meteorites began to retain xenon indicate that the galactic age is between 8.0 and 8.8 billion years, with the initial "prompt" synthesis accounting for 81 to 89 percent of the total r-process material ever produced, the "last-minute" synthesis contributing between 11 and 13 percent, and 0 to 8 percent occurring in the continuous mode. The time interval between the isolation of the solar nebula from galactic r-process and the onset of xenon retention in meteorites lies between 176 and 179 million years. PMID- 17731484 TI - Moon: infrared studies of surface composition. AB - Infrared reflectance studies of small lunar regions reveal several absorption bands which match those of ferrous iron in laboratory spectra of olivines and orthopyroxenes. The craters Kepler and Aristarchus exhibit absorption bands suggestive of orthopyroxene, whereas the background mare material shows a band probably due to olivine. PMID- 17731485 TI - Sulfur Melting and Polymorphism under Pressure: Outlines of Fields for 12 Crystalline Phases. AB - The polymorphism of sulfur has been investigated by static and dynamic methods up to 500 degrees C at 35 kilobars and up to 350 degrees C at 100 kilobars. The melting curve of sulfur to 31 kilobars and phase boundaries of the so-called "4.04-angstrom phase" have been determined. Evidence has been obtained for phase fields of nine new high-pressure forms of sulfur. PMID- 17731486 TI - Galactic water vapor emission: further observations of variability. AB - Recent observations of the 1.35-centimeter line emission of water vapor from galactic sources show short-term variability in the spectra of several sources. Two additional sources, Cygnus 1 and NGC 6334N, have been observed, and the spectra of W49 and VY Canis Majoris were measured over a wider range of radial velocity. PMID- 17731487 TI - Spectrographic detection of topographic features on Mars. AB - Observations of the martian carbon dioxide band at 1.05 microns made with a three channel multislit spectrophotometer indicate gross height variations in the vicinity of Syrtis Major and surrounding desert regions. Syrtis Major appears to be very high with essentially no detectable carbon dioxide above it. The data appear to confirm local trends and, in magnitude at least, the large variations of height found in earlier radar observations. A one-to-one correlation of height with albedo is not evident in the results. Elevated areas are found in both desert and dark regions. In several regions dark areas are associated with relatively steep slopes. PMID- 17731488 TI - Massive internal fracture of an amorphous polyester. AB - When amorphious polyethylene terephthalate is subjected to a tensile load of 2 to 4 x 10(8) dynes per square centimeter wthin the approximate temperature range 40 degrees to 70 degrees C, an unusual optical effect occurs. The transparent polymer film is suddenly transformed into a brilliantly reflecting strip with the luster of silver. Extensive formation of voids accounts for the unorthodox behavior. PMID- 17731489 TI - Coesite from the richat dome, mauritania: a misidentification. AB - The "shattered sandstone" from Richat reported to contain coesite is a tectonic breccia and probably represents a shear zone developed during the structural doming. An optical and x-ray examination of concentrates from this breccia demonstrated that the supposed x-ray reflections of coesite are actually due to barite, introduced into the permeable crushed zone by groundwater. PMID- 17731490 TI - Macquarie island and the cause of oceanic linear magnetic anomalies. AB - Macquarie Islands is formed of probably Pliocene oceanic crust. Intruded into pillow lavas is a belt of harzburgite and layered gabbro mnasses cut by dike swarms. Similar belt-like structures may cause the linear magnetic anomalies of the ocean. PMID- 17731491 TI - Program aaas annual meeting, Boston, massachusetts. PMID- 17731492 TI - Aaas annual meeting. PMID- 17731494 TI - Sea-level canal symposium. PMID- 17731493 TI - Approaches to policy sciences. PMID- 17731495 TI - This Week in SCIENCE. PMID- 17731496 TI - The land of the dammed. PMID- 17731497 TI - Erratum. AB - The color photograph accompanying a ScienceScope item on computational mechanics (18 Oct., p. 365) should have been credited to the San Diego Supercomputing Center. The photograph is a graphic rendering of the brain and not a simulation of Alzheimer's disease, as the caption suggested. PMID- 17731498 TI - Clarification. AB - In the cover caption for the issue of 6 September (p. 1069), the magnification for the image of the mite Proctlaelaps regalis was approximately 400 times its actual body size (actual length was about 500 micrometers). PMID- 17731500 TI - Sciencescope. PMID- 17731499 TI - PCBs in the Environment. PMID- 17731501 TI - Consensus report draws fire from both extremes. PMID- 17731502 TI - "Third wave": roiling the waters. PMID- 17731503 TI - Students Thwart USDA Pest Plan. PMID- 17731504 TI - Catching some (cosmic) rays. PMID- 17731505 TI - Rating University R&D (cont.). PMID- 17731506 TI - Questions raised on math rankings. PMID- 17731507 TI - Primatologists band together. PMID- 17731508 TI - Relaying science to the people. PMID- 17731510 TI - The sound of one dune booming. PMID- 17731509 TI - An ice cap on the hottest planet? PMID- 17731511 TI - Putting Einstein to the Test--in Space. PMID- 17731512 TI - Extinction potpourri: killers and victims: plate tectonics as a driver of evolution. PMID- 17731513 TI - Extinction potpourri: killers and victims: where to run from a mass extinction? PMID- 17731514 TI - Extinction potpourri: killers and victims: looks like the yucatan holds a killer crater. PMID- 17731515 TI - Report Card on Crewdson's Reporting. PMID- 17731516 TI - Changes in the west antarctic ice sheet. AB - The portion of the West Antarctic ice sheet that flows into the Ross Sea is thinning in some places and thickening in others. These changes are not caused by any current climatic change, but by the combination of a delayed response to the end of the last global glacial cycle and an internal instability. The near-future impact of the ice sheet on global sea level is largely due to processes internal to the movement of the ice sheet, and not so much to the threat of a possible greenhouse warming. Thus the near-term future of the ice sheet is already determined. However, too little of the ice sheet has been surveyed to predict its overall future behavior. PMID- 17731517 TI - Electronic correlation effects and superconductivity in doped fullerenes. AB - A theory of the electronic properties of doped fullerenes is proposed in which electronic correlation effects within single fullerene molecules play a central role, and qualitative predictions are made which, if verified, would support this hypothesis. Depending on the effective intrafulllerene electron-electron repulsion and the interfullerene hopping amplitudes (which should depend on the dopant species, among other things), the calculations indicate the possibilities of singlet superconductivity and ferromagnetism. PMID- 17731518 TI - X-ray Damage to CF3CO2-Terminated Organic Monolayers on Si/Au: Principal Effect of Electrons. AB - The relative importance of x-rays alone and of x-ray-generated primary and secondary electrons in damaging organic materials was explored by use of self assembled monolayers (SAMs) on multilayer thin-film supports. The substrates were prepared by the deposit of thin films of silicon (0, 50, 100, and 200 angstroms) on thick layers of gold (2000 angstroms). These systems were supported on chromium-primed silicon wafers. Trifluoroacetoxy-terminated SAMs were assembled on these substrates, and the samples were irradiated with common fluxes of monochromatic aluminum K(alpha) x-rays. The fluxes and energy distributions of the electrons generated by interactions of the x-rays with the various substrates, however, differed. The substrates that emitted a lower flux of electrons exhibited a slower loss of fluorine from the SAMs. This observation indicated that the electrons-and not the x-rays themselves-were largely responsible for the damage to the organic monolayer. PMID- 17731519 TI - Scanning tunneling microscopy of galena (100) surface oxidation and sorption of aqueous gold. AB - Scanning tunneling microscopy was used to characterize the growth of oxidized areas on galena (100) surfaces and the formation of gold islands by the reductive adsorption of AuCl(4)(-) from aqueous solution. The gold islands and galena substrate were distinguished by atomic resolution imaging and tunneling spectroscopy. Oxidized areas on galena have [110]-trending boundaries; gold islands elongate along [110] directions. However, there are no obvious structural registry considerations that would lead to elongation of gold islands in a [110] direction. Instead, it is probable that a direct coupling of gold reduction and sulfide surface oxidation controls the initial formation of gold islands. Gold islands grow less quickly on preoxidized galena surfaces and show no preferred direction of growth. PMID- 17731520 TI - Hydrogen-helium mixtures at megabar pressures: implications for jupiter and saturn. AB - Models of Jupiter and Saturn postulate a central rock core surrounded by a fluid mixture of hydrogen and helium. These models suggest that the mixture is undergoing phase separation in Saturn but not Jupiter. State-of-the-art total energy calculations of the enthalpy of mixing for ordered alloys of hydrogen and helium confirm that at least partial phase separation has occurred in Saturn and predict that this process has also begun in Jupiter. PMID- 17731522 TI - Long-term history of chesapeake bay anoxia. AB - Stratigraphic records from four sediment cores collected along a transect across the Chesapeake Bay near the mouth of the Choptank River were used to reconstruct a 2000-year history of anoxia and eutrophication in the Chesapeake Bay. Variations in pollen, diatoms, concentration of organic carbon, nitrogen, sulfur, acid-soluble iron, and an estimate of the degree of pyritization of iron indicate that sedimentation rates, anoxic conditions and eutrophication have increased in the Chesapeake Bay since the time of European settlement. PMID- 17731521 TI - Superconductivity in the fullerenes. AB - Intramolecular vibrations strongly scatter electrons near the Fermi-surface in doped fullerenes. A simple expression for the electron-phonon coupling parameters for this case is derived and evaluated by quantum-chemical calculations. The observed superconducting transition temperatures and their variation with lattice constants can be understood on this basis. To test the ideas and calculations presented here, we predict that high frequency H(2) modes acquire a width of about 20% of their frequency in superconductive fullerenes, and soften by about 5% compared to the insulating fullerenes. PMID- 17731523 TI - Magma generation on Mars: amounts, rates, and comparisons with Earth, moon, and venus. AB - Total extrusive and intrusive magma generated on Mars over the last approximately 3.8 billion years is estimated at 654 x 10(6) cubic kilometers, or 0.17 cubic kilometers per year (km(3)/yr), substantially less than rates for Earth (26 to 34 km(3)/yr) and Venus (less than 20 km(3)/yr) but much more than for the Moon (0.025 km(3)/yr). When scaled to Earth's mass the martian rate is much smaller than that for Earth or Venus and slightly smaller than for the Moon. PMID- 17731525 TI - The AAAS Annual Meeting. PMID- 17731524 TI - Indole-3-Acetic Acid Biosynthesis in the Mutant Maize orange pericarp, a Tryptophan Auxotroph. AB - The maize mutant orange pericarp is a tryptophan auxotroph, which results from mutation of two unlinked loci of tryptophan synthase B. This mutant was used to test the hypothesis that tryptophan is the precursor to the plant hormone indole 3-acetic acid (IAA). Total IAA in aseptically grown mutant seedlings was 50 times greater than in normal seedlings. In mutant seedlings grown on media containing stable isotopelabeled precursors, IAA was more enriched than was tryptophan. No incorporation of label into IAA from tryptophan could be detected. These results establish that IAA can be produced de novo without tryptophan as an intermediate. PMID- 17731527 TI - Collections and causes. PMID- 17731526 TI - The burden of genetic load. PMID- 17731528 TI - Vignetts from physics. PMID- 17731529 TI - Superconducting devices. PMID- 17731530 TI - Plasmas close at hand. PMID- 17731531 TI - Products & materials. PMID- 17731532 TI - SCIENCE NEWS. PMID- 17731533 TI - THE EXPANDING UNIVERSE. PMID- 17731534 TI - OBITUARY. PMID- 17731535 TI - SHOULD SCIENTIFIC DISCOVERIES BE PATENTED? PMID- 17731536 TI - POTASSIUM PERMANGANATE AS AN ANTIDOTE FOR SNAKE VENOM. PMID- 17731537 TI - MYOESTHESIS AND "IMAGELESS THOUGHT". PMID- 17731538 TI - UNDERGROUND WATER AS A TRANSPORTING AGENT FOR GASOLINE. PMID- 17731539 TI - PRESERVATION OF BACTERIAL CULTURES UNDER LIQUID PARAFFIN. PMID- 17731540 TI - SOME NOTES ON EMBRYOLOGICAL TECHNIQUE. PMID- 17731542 TI - THE APPARENT EXISTENCE OF EASILY DEFLECTABLE POSITIVES. PMID- 17731541 TI - THE CULTIVATION OF NYCTOTHERUS OVALIS AND ENDAMOEBA BLATTAE. PMID- 17731543 TI - PLASMA PHOSPHATASE IN DAIRY COWS SUFFERING FROM FLUOROSIS. PMID- 17731544 TI - MICRO MOTION PICTURES OF B. SHIGAE GROWING UNDER CONDITIONS FAVORING FILTERABILITY AND LIFE CYCLE FORMS. PMID- 17731545 TI - An unpublished reply. PMID- 17731546 TI - Centennial "fireworks". PMID- 17731547 TI - Mercury in the ocean. PMID- 17731548 TI - Zero--what does it mean? PMID- 17731549 TI - Strong stellar winds. AB - The hottest and most luminous stars lose a substantial fraction of their mass in strong stellar winds. These winds not only affect the evolution of the star, they also carve huge expanding cavities in the surrounding interstellar medium, possibly affecting star formation. The winds are probably driven by radiation pressure, but uncertainties persist in their theoretical description. Strong x ray sources associated with a few of these hot stars may be used to probe the stellar winds. The nature of the weak x-ray sources recently observed to be associated with many of these stars is uncertain. It is suggested that roughly 10 percent of the luminous hot stars may have as companions neutron stars or black holes orbiting within the stellar winds. PMID- 17731551 TI - Materials science. PMID- 17731550 TI - Potato protoplasts in crop improvement. AB - Clonal populations regenerated from single-leaf cell protoplasts of the potato cultivar ;Russet Burbank' display a high frequency of variation for several horticultural and disease resistance characters. Observations over a period of three tuber generations suggest stable changes in tuber shape, yield, and maturity date, in photo-period requirements for flowering, and in plant morphology. Enhanced resistance to early blight (Alternaria solani) and late blight (Phytophthora infestans) diseases also regularly occurs within regenerated populations. These findings are discussed in the context of possible application to varietal improvement, particularly as they pertain to asexually propagated plants. PMID- 17731553 TI - Carter Creates a Sinewy NRC. PMID- 17731552 TI - The Osage Oil Cover-up. PMID- 17731554 TI - Is science and engineering training adequate? PMID- 17731555 TI - High-tech sales to u.s.s.R. Further reduced. PMID- 17731556 TI - Psychiatrists study three-mile trauma. PMID- 17731557 TI - What is siberian ulcer doing in sverdlovsk? PMID- 17731558 TI - Coastal upwelling: physical factors feed fish. PMID- 17731559 TI - Pere village remembers margaret mead. PMID- 17731560 TI - Fifth annual r&d public policy colloquium. PMID- 17731561 TI - Chile hosts arid lands congress. PMID- 17731562 TI - Grants offered to foreign graduate students to attend r&d colloquium. PMID- 17731563 TI - Obituaries. PMID- 17731564 TI - Science in sri lanka. PMID- 17731565 TI - Birds of prey. PMID- 17731566 TI - Population biology. PMID- 17731567 TI - Volcanoes. PMID- 17731568 TI - Capacities of young children. PMID- 17731569 TI - Lunar magnetic anomalies and surface optical properties. AB - For typical solar wind conditions, lunar magnetic anomalies with dipole moments m >> 5 x 10(13) gauss-cubic centimeters will strongly deflect the solar wind, producing local plasma voids at the lunar surface. The correlation of the largest observed anomalies (m approximately 10(16) gauss-cubic centimeters) with unusual, relatively high albedo surface features may therefore imply that solar wind ion bombardment is an important determinant of the optical properties of the lunar surface. PMID- 17731570 TI - Is the sun shrinking? AB - Observations of 23 transits of Mercury in front of the sun between 1736 and 1973 show no indication of any significant change in the diameter of the sun. Regression analysis yields a decrease of the angular diameter, as viewed from the earth, of under 0.3 arc second per century (> 90 percent confidence limit). This limit is incompatible with the 2 arc seconds per century decrease obtained by Eddy for the equatorial diameter from direct observations made at the Greenwich Observatory and at the U.S. Naval Observatory. PMID- 17731571 TI - Formamidine pesticides: octopamine-like actions in a firefly. AB - The formamidine pesticide chlordimeform and its N-demethylated metabolites cause the light organ of the firefly Photinus pyralis L. to glow brightly. Monodemethyl chlordimeform is active at doses as low as 5 nanograms per insect when applied topically. This action is postsynaptic and probably involves membrane-bound receptors since cyproheptadine blocks the glows induced by both monodemethyl chlordimeform and octopamine, the putative neurotransmitter in the light organ. The pesticidal and pestistatic properties of the formamidines may result from actions on octopaminergic systems. PMID- 17731573 TI - THE UNIFICATION OF AMERICAN BOTANY. PMID- 17731572 TI - Serotonin and octopamine produce opposite postures in lobsters. AB - Serotonin and octopamine, injected into the circulation of freely moving lobsters and crayfish, produce opposite behavioral effects. Octopamine injection produces sustained extension of the limbs and abdomen; serotonin injection produces sustained flexion. Neurophysiological analyses show that these postures can be accounted for by opposing, coordinated effects of these amines on patterns of motoneuron activity recorded from the ventral nerve cord. PMID- 17731574 TI - THE ELEMENTARY COURSE IN ZOOLOGY-IS IT SATISFACTORY? PMID- 17731575 TI - WALLACE CLEMENT WARE SABINE. PMID- 17731577 TI - PATENT REFORM PROSPECTS. PMID- 17731576 TI - A STANDARD SCIENTIFIC ALPHABET. PMID- 17731578 TI - FIELD WORK IN ARIZONA. PMID- 17731580 TI - SCIENCE IN THE BRITISH PARLIAMENT. PMID- 17731579 TI - DR. MOODIE'S OPISTHOTONUS. PMID- 17731582 TI - UNHEATED EGG-YOLK MEDIA. PMID- 17731581 TI - NOTE ON THE TECHNIQUE OF SOLUTION CULTURE EXPERIMENTS WITH PLANTS. PMID- 17731583 TI - "Polywater" is hard to swallow. PMID- 17731584 TI - Letters to the editor. PMID- 17731585 TI - Marital success of scientists. PMID- 17731586 TI - U.s. Radio astronomy in decline. PMID- 17731587 TI - Nuclear fission revisited. PMID- 17731588 TI - Senator william proxmire: what makes him run? PMID- 17731589 TI - Nixon proposes channel sanctuary. PMID- 17731590 TI - Asteroid vesta: spectral reflectivity and compositional implications. AB - The spectral reflectivity (0.30 to 1.10 microns) of several asteroids has been measured for the first time. The reflection spectrum for Vesta contains a strong absorption band centered near 0.9 micron and a weaker absorption feature between 0.5 and 0.6 micron. The reflectivity decreases strongly in the ultraviolet. The reflection spectrum for the asteroid Pallas and probably for Ceres does not contain the 0.9-micron band. Vesta shows the strongest and best-defined absorption bands yet seen in the reflection spectrum for the solid surface of an object in the solar system. The strong 0.9-micron band arises from electronic absorptions in ferrous iron on the M2 site of a magnesian pyroxene. Comparison with laboratory measurements on meteorites and Apollo 11 samples indicates that the surface of Vesta has a composition very similar to that of certain basaltic achondrites. PMID- 17731591 TI - Chlorophyll derivatives in middle eocene sediments. AB - Chloroform extracts of middle Eocene brown coal were made; the chlorophyll derivatives obtained were separated chromatographically. The visible light spectrum, chromatographic behavior, HCl number, infrared spectrum, and mass spectrum of one of the pigments extracted is indicative of methyl pheophorbide a. This is the oldest occurrence of fossil phorbins reported. PMID- 17731592 TI - Pollen sequence from late quaternary sediments in yellowstone park. AB - A radiocarbon-dated pollen diagram from a depression near the end of the southeast arm of Yellowstone Lake, Wyoming, records the vegetation sequence from the retreat of Late Wisconsin (Pinedale) ice to the present time. The tundra Picea-Abies-Pinus albicaulis (spruce-fir-whitebark pine) parkland vegetation inferred during late glacial time changed rapidly to a Pinus contorta (lodgepole pine) forest shortly before 11,550 carbon-14 years ago, suggesting a warming trend at that time. The Pinus contorta forest persisted with minor modification throughout postglacial time. PMID- 17731593 TI - High-magnesian calcite: leaching of magnesium in the deep sea. AB - The high-magnesian calcite fraction of a shallow-water carbonate sand was converted to low-magnesian calcite after transport to the deep sea; strontium was also leached from the carbonate. Oxygen isotopic ratios indicate that loss of magnesium and strontium took place during recrystallization of the carbonate in the deep sea; this process did not alter textures of skeletal fragments. Previously, high-magnesian, calcite was thought only to dissolve in the deep sea. PMID- 17731594 TI - Interstellar Scattering of Pulsar Radiation and Its Effect on the Spectrum of NP0532. AB - Angular scattering in the interstellar medium results in multipath dispersion which can amount to more than one pulse period for pulsars of short period and high dispersion measure. The dispersion, if operative, imposes on the pulsation flux a cutoff inversely proportional to the fourth power of the observing wavelength. The low-frequency pulse shape of pulsar NP0532 suggests that this pulsar is subject to such scattering and that the observed low-frequency cutoff in the apparent spectrum is not an intrinsic property of the pulsar. In fact, there is evidence that NP0532 may be identified as the compact, low-frequency source in the Crab Nebula and that the pulsar may radiate in accordance with its high-frequency spectrum down to frequencies as low as 10 megahertz, although the periodic time variations are suppressed by the scattering below 100 megahertz. PMID- 17731595 TI - Attenuation on an Earth-space path measured in the wavelength range of 8 to 14 micrometers. AB - A telescope operating over the wavelength range of 8 to 14 micrometers has been added to the Crawford Hill sun tracker for the purpose of measuring attenuation in that atmospheric window. Over a 9-month period the attenuation (typically from clouds) exceeded 10, 20, and 30 decibels for 48, 43, and 34 percent of the time. PMID- 17731596 TI - Scanning electron microscopy of developing plant organs. AB - Shoot apices and young meristematic leaves can be examined directly with the scanning electron microscope without prior fixation or metal coating. The form of the shoot apex, cellular organization, andleaf arrangement (phyllotaxis) can be observed, perphaps as they have never been visualized before. PMID- 17731597 TI - Forthcoming events. PMID- 17731598 TI - THE USE OF OIL ABOARD UNITED STATES NAVAL VESSELS. PMID- 17731599 TI - THE THOMSON-HOUSTON ROAD IN BANGOR, ME. PMID- 17731601 TI - PROGRESS OF ENGINEERING. PMID- 17731600 TI - A HISTORY OF HABITATIONS. PMID- 17731602 TI - NOTABLE DERELICTS IN THE NORTH ATLANTIC. PMID- 17731603 TI - THE GRAIN PLANT-LOUSE IN OHIO. PMID- 17731604 TI - THE BRUCE PHOTOGRAPHIC TELESCOPE. PMID- 17731605 TI - CHARITY AND KNOWLEDGE. PMID- 17731606 TI - INDUSTRIAL NOTES. PMID- 17731607 TI - SCIENCE NEWS. PMID- 17731608 TI - THE PHYSICAL SCIENCES. PMID- 17731609 TI - THE SUPREME INTELLECTUAL OBLIGATION. PMID- 17731610 TI - ADVANCING GLACIERS IN ALASKA. PMID- 17731611 TI - MOVEMENT OF PIGMENT GRANULES IN CHROMATOPHORES. PMID- 17731613 TI - THE UNITED STATES BOTANIC GARDEN. PMID- 17731614 TI - AN EXTRACTOR FOR FLUID SYSTEMS. PMID- 17731612 TI - GERMAN PERIODICALS AND AMERICAN LIBRARIES. PMID- 17731615 TI - DECREASE IN GOVERNMENT APPROPRIATIONS FOR ENTOMOLOGICAL WORK. PMID- 17731616 TI - ST. LOUIS ENCEPHALITIS. PMID- 17731618 TI - THE EFFECT OF X-RAYS ON GROWTH SUBSTANCE AND PLANT GROWTH. PMID- 17731617 TI - AN ATTEMPT TO ISOLATE VITAMIN A. PMID- 17731620 TI - Marine transplantations. PMID- 17731621 TI - The hubble variable? PMID- 17731619 TI - Meetings in Mexico. PMID- 17731623 TI - The saga of american universities: the role of science. PMID- 17731622 TI - Consumer product safety. PMID- 17731625 TI - Agriculture: NAS Panel Charges Inept Management, Poor Research. PMID- 17731624 TI - The apollo 16 lunar samples: petrographic and chemical description. AB - The preliminary characterization of the rocks and soils returned from the Apollo 16 site has substantiated the inference that the lunar terra are commonly underlain by plagioclase-rich or anorthositic rocks. No evidence has been found for volcanic rocks underlying the regolith in the Apollo 16 region. In their place, we have found anorthositic rocks that are thoroughly modified by crushing and partial melting. The textural and chemical variations in these rocks provide some evidence for the existence of anorthositic complexes that have differentiated on a scale of tens to hundreds of meters. The occurrence of deep seated or plutonic rocks in place of volcanic or pyroclastic materials at this site suggests that the inference from physiographic evidence that the latter materials are widespread in terra regions may be incorrect. Several additional, more specific conclusions derived from this preliminary examination are: 1) The combination of data from the Descartes region with data from the orbital x-ray fluorescence experiment indicates that some backside, highland regions are underlain by materials that consist of more than 80 percent plagioclase. 2) The soil or upper regolith between North Ray and South Ray has not been completely homogenized since the time of formation of these craters. 3) The chemistry of the soil indicates that rocks rich in potassium, uranium, and thorium, similar to those that prevail at the Fra Mauro site, are relatively abundant (10 to 20 percent) in the Descartes region. 4) The K/U ratio of the lunar crust is similar to that of the KREEP basalts. 5) The carbon content of the premare lunar crust is even lower than that of the mare volcanic rocks. PMID- 17731626 TI - Congress May Investigate NAS. PMID- 17731627 TI - NASA Satellite Project: The Boss Is a Woman. PMID- 17731629 TI - Power gas and combined cycles: clean power from fossil fuels. PMID- 17731628 TI - Wilson international center: a washington connection. PMID- 17731630 TI - Apollo 16 exploration of descartes: a geologic summary. AB - The Cayley Plains at the Apollo 16 landing site consist of crudely stratified breccias to a depth of at least 200 meters, overlain by a regolith 10 to 15 meters thick. Samples, photographs, and observations by the astronauts indicate that most of the rocks are impact breccias derived from an anorthositegabbro complex. The least brecciated members of the suite include coarse-grained anorthosite and finer-grained, more mafic rocks, some with igneous and some with metamorphic textures. Much of the traverse area is covered by ejecta from North Ray and South Ray craters, but the abundance of rock fragments increases to the south toward the younger South Ray crater. The Descartes highlands, a distinct morphologic entity, differ from the adjacent Cayley formation more in physiographic expression than in lithologic character. PMID- 17731631 TI - Volatile-rich lunar soil: evidence of possible cometary impact. AB - A subsurface Apollo 16 soil, 61221, is much richer in volatile compounds than soils from any other locations or sites as shown by thermal analysis-gas release measurements. A weight loss of 0.03 percent during the interval 175 degrees to 350 degrees C was associated with the release of water, carbon dioxide, methane, hydrogen cyanide, hydrogen, and minor amounts of hydrocarbons and other species. These volatile components may have been brought to this site by a comet, which may have formed North Ray crater. PMID- 17731632 TI - Breccias from the lunar highlands: preliminary petrographic report on apollo 16 samples 60017 and 63335. AB - Lunar samples 60017,4 and 63335,14 are composed of microbreccias and devitrified glass. These components are predominantly anorthositic, with the exception of a cryptocrystalline clast found in the microbreccia portion of 63335,14 which contains 2.7 percent potassium oxide and 66.7 percent silicon dioxide. The samples have been subjected to extreme shock and thermal metamorphism. The parent materials of the microbreccias include both a coarse-grained anorthosite and a fine-grained subophitic anorthositic gabbro. PMID- 17731633 TI - Spinel troctolite and anorthosite in apollo 16 samples. AB - A spinel troctolite and an anorthosite from the Apollo 16 landing site represent contrasting types of "primitive" lunar cumulates. The two rock types probably formed from the same parent magma type, a high-alumina magnesian basalt, with the troctolite forming earlier by crystal settling, and the anorthosite later, possibly by flotation. PMID- 17731634 TI - Early Cultivated Beans (Phaseolus vulgaris) from an Intermontane Peruvian Valley. AB - Examples of fully domesticated common beans (Phaseolus vulgaris) and lima beans (Phaseolus lunatus) were recovered from deposits in Guitarrero Cave (PAn 14-102) in the Callejon de Huaylas, Ancash, Peru. Carbon-14 dates for stratum II, in which the earliest beans were found, range from 7,680 +/- 280 to 10,000 +/- 300 years before the present. PMID- 17731635 TI - Dichloromethane and lettuce seed germination. PMID- 17731637 TI - ARTIFICIAL LANGUAGES. PMID- 17731636 TI - THE KALAMATH NATION: III.--MYTHOLOGY AND GENERAL ETHNOLOGY. PMID- 17731638 TI - THE LAFAYETTE GRAVELS. PMID- 17731639 TI - ORTHOGRAPHY OF GEOGRAPHICAL NAMES. PMID- 17731640 TI - PRISMATIC SANDSTONE FROM MISSOURI. PMID- 17731641 TI - ELECTRICITY IN AGRICULTURE. PMID- 17731642 TI - The Historical American Exhibition at Madrid. PMID- 17731643 TI - The First Locomotive Run iu America. PMID- 17731644 TI - At What Time were the Galapagos Islands Discovered? PMID- 17731645 TI - THE PRESIDENT'S ADDRESS. PMID- 17731646 TI - THE GENERAL MEETING. PMID- 17731647 TI - OUR SISTER SOCIETIES. PMID- 17731648 TI - THE MATHEMATICAL THEORY OF THE TOP. PMID- 17731649 TI - AN UNPUBLISHED LETTER BY RAFINESQUE. PMID- 17731651 TI - THE 'PRICKLY PEAR.'. PMID- 17731650 TI - STEINER'S 'LOST' MANUSCRIPT OF 1826. PMID- 17731652 TI - A MUD SHOWER. PMID- 17731654 TI - THE HYDROLYSIS AND SYNTHESIS OF ETHYL BUTYRATE BY PLATINUM BLACK. PMID- 17731653 TI - 'NODULES' IN COLORED BLOOD CORPUSCLES. PMID- 17731655 TI - CORRESPONDENCE OF THE LATE PROFESSOR LEIDY. PMID- 17731656 TI - THE CONGER EEL. PMID- 17731657 TI - THE SONG OF BIRDS. PMID- 17731658 TI - THE JACKSON OUTCROPS ON RED RIVER. PMID- 17731659 TI - THE NOMENCLATURE OF THE MONOPHLEBINE COCCIDAE. PMID- 17731660 TI - EPA air pollution standard. PMID- 17731662 TI - Problems. PMID- 17731661 TI - Problems. PMID- 17731663 TI - Federal regulation: what role for universities? PMID- 17731664 TI - Scientific relations with china. PMID- 17731665 TI - Education, science, and technology in china. PMID- 17731666 TI - The chinese scene. PMID- 17731668 TI - Congress seeks new approach to arms control. PMID- 17731667 TI - China: objectives, contradictions, and social currents. PMID- 17731669 TI - Smog's Not So Bad, EPA Decides. PMID- 17731671 TI - Mantle Geochemistry: Probing the Source of the Earth's Crust. PMID- 17731670 TI - The Public Interest versus Lollipops. PMID- 17731672 TI - AAAS Board Visit to China--A Brief Report. PMID- 17731674 TI - AAAS Introduces New Life Insurance Program. PMID- 17731673 TI - Warren weaver 1894-1978. PMID- 17731675 TI - Fourth annual r&d policy colloquium. PMID- 17731676 TI - For the library. PMID- 17731678 TI - Edison centennial symposium planned. PMID- 17731679 TI - Climate project organizing workshop. PMID- 17731677 TI - Chautauqua short course program. PMID- 17731680 TI - AAAS Membership List. PMID- 17731681 TI - A public institution. PMID- 17731682 TI - Life and work of ronald fisher. PMID- 17731684 TI - Flowering plants. PMID- 17731683 TI - Life in thermal habitats. PMID- 17731685 TI - Insects in the city. PMID- 17731686 TI - Postmating reproductive isolation in pseudophryne and the evolutionary significance of hybrid zones. AB - Hybrid zones involving Pseudophryne (Anura: Leptodactylidae) provide direct evidence for the operation of postmating reproductive isolating mechanisms in animals in a natural situation. Significant introgression is prevented by hybrid inviability but there is no evidence for the reinforcement of premating isolating mechanisms. These parapatric hybrid zones are of unknown etiology, but are interpreted as being relatively old and persistent. PMID- 17731687 TI - Manganese nodules on the sea floor: are economic mining operations feasible? PMID- 17731688 TI - PRODUCTS and MATERIALS. PMID- 17731689 TI - SOME GEOLOGICAL FEATURES OF JACKSON PARK, CHICAGO. PMID- 17731690 TI - THE ATMOSPHERES OF THE MOON, PLANETS AND SUN. PMID- 17731691 TI - ON THE LIFE ZONES OF THE ORGAN MOUNTAINS AND ADJACENT REGION IN SOUTHERN NEW MEXICO, WITH NOTES ON THE FAUNA OF THE RANGE. PMID- 17731692 TI - POTTERY ON PUGET SOUND. PMID- 17731694 TI - A MISTAKE IN TEACHING BOTANY. PMID- 17731693 TI - DISPOSAL OF WASTE AT THE WORLD'S COLUMBIAN EXPOSITION. PMID- 17731696 TI - CORAL REEF FORMATION. PMID- 17731695 TI - BIRD NOTES. PMID- 17731697 TI - This week in science. PMID- 17731698 TI - Setting priorities in science. PMID- 17731699 TI - In reply: estimates of species duration. PMID- 17731700 TI - Estimates of species duration. PMID- 17731702 TI - Rethinking Technology's Role in Economic Change: Ambitious effort to evaluate the role of technology in the U.S. economic future indicates need for regulatory reform, shifts in business practice, and emphasis on education. PMID- 17731703 TI - Giving the Muse a Helping Hand: A series of memoirs sponsored by the Sloan Foundation offers scientists' first person perspective on research. PMID- 17731701 TI - Testing the Limits at March 25: The $3.3-billion program to build a hypersonic aerospace plane is facing major technical hurdles; air transport industry shows little interest. PMID- 17731705 TI - National science board elects good and day. PMID- 17731704 TI - Curien returns as French science minister. PMID- 17731706 TI - Soviet satellite in trouble; groups call for ban on orbiting reactors. PMID- 17731708 TI - NSF Appoints Two Assistant Directors. PMID- 17731707 TI - Legislating labs as drug-free workplaces. PMID- 17731709 TI - A Revolution of Ideas in Agricultural Origins: Ideas about the origin of sedentism and agriculture have been changing in recent years, with a greater emphasis on examining the details of sites case by case. PMID- 17731710 TI - Pluto's Orbital Motion Looks Chaotic: The oddest planet seems to have a new distinction: its motion around the sun is irregular to the point of unpredictability. PMID- 17731711 TI - Sampling rare and elusive populations. AB - The sampling of rare and elusive populations is difficult because the costs of locating such populations are substantial and can exceed actual interviewing costs. There are efficient probability methods that have been developed recently that reduce these costs. If the special populations are geographically clustered, efficient sampling involves the rapid location of segments in which no members of the special population are located with the use of Census data, telephone screening, or incomplete lists. Populations that are not geographicaily clustered can be located by network sampling and use of large previously gathered samples. Characteristics of mobile populations such as the homeless can be estimated by capture-recapture methods. PMID- 17731712 TI - Abrupt climate change and extinction events in Earth history. AB - Slowly changing boundary conditions can sometimes cause discontinuous responses in climate models and result in relatively rapid transitions between different climate states. Such terrestrially induced abrupt climate transitions could have contributed to biotic crises in earth history. Ancillary events associated with transitions could disperse unstable climate behavior over a longer but still geologically brief interval and account for the stepwise nature of some extinction events. There is a growing body of theoretical and empirical support for the concept of abrupt climate change, and a comparison of paleoclimate data with the Phanerozoic extinction record indicates that climate and biotic transitions often coincide. However, more stratigraphic information is needed to precisely assess phase relations between the two types of transitions. The climate-life comparison also suggests that, if climate change is significantly contributing to biotic turnover, ecosystems may be more sensitive to forcing during the early stages of evolution from an ice-free to a glaciated state. Our analysis suggests that a terrestrially induced climate instability is a viable mechanism for causing rapid environmental change and biotic turnover in earth history, but the relation is not so strong that other sources of variance can be excluded. PMID- 17731713 TI - Aluminum-induced calcium deficiency syndrome in declining red spruce. AB - Prolonged suppression of cambial growth has apparently caused a decline in radial growth in many mature red spruce, Picea rubens. Surveys indicate that this decline occurs in trees throughout the natural range of red spruce and is independent of elevation, tree size, and age class. In addition, crowns of mature red spruce at high elevations across the northeastern United States have been dying back. Understanding the physiological basis for the growth decline is essential for the judicious management of the red spruce resource. A sequence of events is inferred through which an imbalance of aluminum and calcium in the fine root environment reduces the rate of wood formation, decreases the amount of functional sapwood and live crown, and leaves large trees more vulnerable to extant secondary diseases and insect pests. PMID- 17731714 TI - Antarctic Ozone Depletion Chemistry: Reactions of N2O5 with H2O and HCl on Ice Surfaces. AB - The reactions of dinitrogen pentoxide (N(2)O(5)) with H(2)O and hydrochloric acid (HCl) were studied on ice surfaces in a Knudsen cell flow reactor. The N(2)O(5) reacted on ice at 185 K to form condensed-phase nitric acid (HNO(3)). This reaction may provide a sink for odd nitrogen (NO(x)) during the polar winter, a requirement in nearly all models of Antarctic ozone depletion. A lower limit to the sticking coefficient, gamma, for N(2)O(5) on ice is 1 x 10(-3). Moreover, N(2)O(5) reacted on HCl-ice surfaces at 185 K, with gamma greater than 3 x 10( 3). This reaction, which produced gaseous nitryl chloride (ClNO(2)) and condensed phase HNO(3), proceeded until all of the HCl within the ice was depleted. The ClNO(2), which did not react or condense on ice at 185 K, can be readily photolyzed in the Antarctic spring to form atomic chlorine for catalytic ozone destruction cycles. The other photolysis product, gaseous nitrogen dioxide (NO(2)), may be important in the partitioning of NO(x) between gaseous and condensed phases in the Antarctic winter. PMID- 17731715 TI - Evidence for highly reflecting materials on the surface and subsurface of vensus. AB - Radar images at a 12.5-centimeter wavelength made with the Goldstone radar interferometer in 1980 and 1986, together with lunar radar images and recent Venera 15 and 16 data, indicate that material on the surface and subsurface of Venus has a Fresnel reflectivity in excess of 50 percent. Such high reflectivities have been reported on the surface in mountainous regions. Material of high reflectivity may also underlie lower reflectivity surficial materials of the plains regions, where it has been excavated by impact cratering in some areas. PMID- 17731716 TI - In reply: carcinogenic risk estimation. PMID- 17731717 TI - Cult Archaeology and Creationism. Understanding Pseudoscientific Beliefs about the Past. Francis B. Harrold and Raymond A. Eve, Eds. University of Iowa Press, Iowa City, 1987. xii, 163 pp., illus. $20. Based on a symposium, 1986. PMID- 17731718 TI - Darwin's Forgotten Defenders. The Encounter between Evangelical Theology and Evolutionary Thought. David N. Livingstone. Eerdmans, Grand Rapids, MI, and Scottish Academic Press, Edinburgh, 1987. xii, 210 pp., illus. Paper, $10.95. PMID- 17731719 TI - The Comparative Reception of Relativity. Thomas F. Glick, Ed. Reidel, Dordrecht, 1987 (U.S. distributor, Kluwer, Norwell, MA). viii, 412 pp. $79. Boston Studies in the Philosophy of Science, vol. 103. Based on a colloquium, Boston, MA, March 1983. PMID- 17731721 TI - Industry and Ideology. IG Farben in the Nazi Era. Peter Hayes. Cambridge University Press, New York, 1987. xxviii, 411 pp., illus. $39.50. PMID- 17731720 TI - Nuclear Fear. A History of Images. Spencer R. Weart. Harvard University Press, Cambridge, MA, 1988. xvi, 535 pp., illus. $29.50. PMID- 17731722 TI - Race Hygiene and National Efficiency. The Eugenics of Wilhelm Schallmayer. Sheila Faith Weiss. University of California Press, Berkeley, 1988. xii, 245 pp. $35. PMID- 17731724 TI - Beyond Monopoly. Lawyers, State Crises, and Professional Empowerment. Terence C. Halliday. University of Chciago Press, Chicago, 1987. xx, 388 pp., illus. $29.95. PMID- 17731725 TI - The AIDS Bureaucracy. Sandra Panem. Harvard University Press, Cambridge, MA, 1988. xiv, 194 pp. $22.50; paper, $9.95. PMID- 17731726 TI - Law and the Shaping and Public Education, 1785-1954. David Tyack, Thomas James, and Aaaron Benavot. University of Wisconsin Press, Madison, WI, 1987. xii, 259 pp. $25. PMID- 17731728 TI - Return to Aztian. The Social Process of International Migration from Western Mexico. Douglas S. Massey, Rafael Alarcon, Jorge Durand, and Humberto Gonzalez. University of California Press, Berkeley, CA, 1987. x, 335 pp., illus. $37.50. Studies in Demography, vol. 1. PMID- 17731727 TI - Survey Research in the United States. Roots and Emergence, 1890-1960. Jean N. Converse. University of California Press, Berkeley, 1987. xvi, 564 pp., illus. $50. PMID- 17731730 TI - Workers, Managers, and Technological Change. Emerging Patterns of Labor Relations. Daniel B. Cornfield, Ed. Plenum, New York, 1987. xxii, 362 pp. $37.50. Plenum Studies in Work and Industry. PMID- 17731729 TI - Adolescent Mothers in Later Life. Frank F. Furstenberg, Jr., J. Brooks-Gunn, and S. Philip Morgan. Cambridge University Press, New York, 1987. xiv, 204 pp., illus. $27.95. Human Development in Cultural and Historical Contexts. PMID- 17731731 TI - Fasting Girls. The Emergence of Anorexia Nervosa as a Modern Disease. Joan Jacobs Brumberg. Harvard University Press, Cambridge, MA, 1988. x, 366 pp., illus. $25. PMID- 17731732 TI - Women, Work, and Technology. Transformations. Barbara Drygulski Wright and six others, Eds. University of Michigan Press, Ann Arbor, MI, 1987. viii, 387 pp. $29; paper, $13.50. Women and Culture Series. Based on a conference, Storrs, CT, Oct. 1984. PMID- 17731733 TI - Gender at Work. The Dynamics of Job Segregation by Sex during World War II. Ruth Milkman. University of Illinois Press, Urbana, IL, 1987. xvi, 213 pp., illus. $32.50; paper, $8.95. The Working Class in American History. PMID- 17731734 TI - Alvarez. Adventures of a Physicist. Luis W. Alvarez. Basic Books, New York, 1987. xii, 292 pp. + plates. $19.95; Discovering Alvarez. Selected Works of Luis W. Alvarez, with Commentary by His Students and Colleagues. W. Peter Trower, Ed. University of Chicago Press, Chicago, 1987. x, 272 pp., illus., + plates. $37.50. PMID- 17731735 TI - In Quest of Panacea. Successes and Failures of Yellapragada SubbaRow. S. P. K. Gupta with Edgar L. Milford. Evelyn, New Delhi, India, 1987 (available from Preethi Kiran, 260 Avon Road, Devon, PA). 311 pp. $15. PMID- 17731736 TI - Simple Curiosity. Letters from George Gaylord Simpson to His Family, 1921-1970. Leo F. Laporte, Ed. University of California Press, Berkeley, CA, 1988. x, 340 pp., illus. $29.95. PMID- 17731737 TI - The Physics of Time Reversal. Robert G. Sachs. University of Chicago Press, Chicago, 1987. xvi, 309 pp., illus. $55; paper, $23. PMID- 17731738 TI - Three Hundred Years of Gravitation. S. W. Hawking and W. Israel, Eds. Cambridge University Press, New York, 1987. xiv, 684 pp., illus. $69.50. PMID- 17731739 TI - Georges Bank. Richard H. Backus, Ed. MIT Press, Cambridge, MA, 1987. x, 593 pp., illus., + chart in pocket. $225. PMID- 17731741 TI - The Evolution of Sex. An Examination of Current Ideas. Richard E. Michod and Bruce R. Levin, Eds. Sinauer, Sunderland, MA, 1987. x, 342 pp., illus. $55; paper, $29.95. PMID- 17731742 TI - Oasis in Space. Earth History from the Beginning. Preston Cloud. Norton, New York, 1988. xviii, 508 pp., illus. $29.95. Commonwealth Book Fund Program. PMID- 17731740 TI - Paleokarst. N. P. James and P. W. Choquette, Eds. Springer-Verlag, New York, 1987. xii, 416 pp., illus. $64. Based on a symposium, Golden, CO, 1985. PMID- 17731743 TI - The Evolution of Individuality. Leo W. Buss. Princeton University Press, Princeton, NJ, 1988. xvi, 203 pp., illus. $40; paper, $12.95. PMID- 17731745 TI - Frogfishes of the World. Systematics, Zoogeography, and Behavioral Ecology. Theodore W. Pietsch and David B. Grobecker. Stanford University Press, Stanford, CA, 1987. xxiv, 420 pp., illus., + plates. PMID- 17731744 TI - The Natural History of Nautilus. Peter Douglas Ward. Allen and Unwin, Winchester, MA, 1987. xiv, 267 pp., illus. $34.95; Nautilus. The Biology and Paleobiology of a Living Fossil. W. Bruce Saunders and Neil H. Landman, Eds. Plenum, New York, 1988. xxviii, 632 pp., illus., + plates. $95. Topics in Geobiology, vol. 6. PMID- 17731746 TI - Primate Societies. Barbara B. Smuts, Dorothy L. Cheney, Robert M. Seyfarth, Richard W. Wrangham, and Thomas T. Struhsaker, Eds. University of Chicago Press, Chicago, IL, 1987. xii, 578 pp., illus. $70; paper, $27.50. PMID- 17731748 TI - The Dreaming Brain. J. Allan Hobson. Basic Books, New York, 1988. xvi, 319 pp., illus. $22.95. PMID- 17731747 TI - Studies of Mascarene Island Birds. A. W. Diamond, Ed. Cambridge University Press, New York, 1987. vi, 458 pp., illus. $125. PMID- 17731749 TI - Memory Traces in the Brain. Daniel L. Alkon. Cambridge University Press, New York, 1988. x, 190 pp., illus. $39.50; paper, $14.95. PMID- 17731750 TI - Cultural Models in Language and Thought. Dorothy Holland and Naomi Quinn, Eds. Cambridge University Press, New York, 1987. xii, 400 pp. $49.50; paper, $15.95; Discourse and the Social Life of Meaning. Phyllis Pease Chock and June R. Wyman, Eds. Smithsonian Institution Press, Washington, DC, 1986. 232 pp., illus. $22.50. Anthropological Society of Washington Series. PMID- 17731751 TI - The Question of the Commons. The Culture and Ecology of Communal Reources. Bonnie J. McCay and James M. Acheson, Eds. University of Arizona Press, Tucson, 1987. xvi, 439 pp., illus. $35. Arizona Studies in Human Ecology. PMID- 17731752 TI - Lithic Studies among the Contemporary Highland Maya. Brian Hayden, Ed. University of Arizona Press, Tucson, AZ, 1987. xii, 387 pp., illus. $35; Stone Tool Use of Cerros. The Ethnoarchaeological and Use-Wear Evidence. Suzanne M. Lewenstein. University of Texas Press, Austin, TX, 1987. x, 228 pp., illus. $42.50. PMID- 17731753 TI - Vectors of Death. The Archaeology of European Contact. Ann F. Ramenofsky. University of New Mexico Press, Albuquerque, 1988. xvi, 300 pp., illus. $27.50. PMID- 17731754 TI - The Walnut Street Prison Workshop. A Test Study in Historical Archaeology Based on Field Investigation in the Garden Area of the Athenaeum of Philadelphia. John L. Cotter, Roger W. Moss, Bruce C. Gill, and Jiyul Kim. The Athenaeum of Philadelphia, Philadelphia, 1988. 95 pp., illus. Paper, $7.50. PMID- 17731755 TI - Books Reviewed in Science 22 May 1986 through 13 May 1988. PMID- 17731756 TI - Aaas annual meeting. PMID- 17731757 TI - Products & materials. PMID- 17731759 TI - Large-scale integration AI the revolution in electronics. PMID- 17731758 TI - Our nation and the sea. PMID- 17731761 TI - A Private University: Academics Seek To Set Up Britain's First. PMID- 17731760 TI - The Hornig Years: Did LBJ Neglect His Science Adviser? PMID- 17731762 TI - Hydrocarbons of blue-green algae: geochemical signfficance. AB - The hydrocarbon compositions of 11 species of blue-green algae are simple and qualitatively similar. Three marine coccoids contain only monoenoic and dienoic C(19) hydrocarbons. Hydrocarbons of the remaining eight species are C(15) to C(18). Hydrocarbons of higher molecular weight (C(20) or more) were not detected. Blue-green algae do not appear to be the source material for the longchain (greater than 20 carbons) hydrocarbons found in ancient sediments. PMID- 17731763 TI - Solubility in water of normal c9 and c10, alkane hydrocarbons. AB - A new method for equilibrating water containing alkane hydrocarbons with a gas phase and analyzing the gas for hydrocarbon content by gas chromatography extends analytical sensitivity to better than 0.1 part per billion. The solubilities at 25 degrees C of the normal C(9) (220 parts per billion) and C(10) (52 parts per billion) alkanes decrease with increasing carbon number. A discontinuity occurs at the normal C(11), alkane, probably because of a change from true solubility (molecular dispersion) to accommodation (aggregation). PMID- 17731764 TI - Mimicry of hymenoptera by beetles with unconventional flight. AB - Flower-visiting beetles of the genus Acmaeodera (Buprestidae) bear a striking resemblance to Hymenoptera in flight. Unlike most other beetles, they fly with their membranous hindwings only, and their forewings, which are inseparably coupled and permanently held over the abdomen, bear color markings commonly found on the abdomens of bees and wasps. PMID- 17731765 TI - Aquaculture: amplification and correction. PMID- 17731766 TI - Radioactive Peptide available. PMID- 17731767 TI - Stomatal opening: role of potassium uptake. PMID- 17731768 TI - THE EFFECTS OF CIVILIZATION ON OUR BIRDS. PMID- 17731769 TI - THE DUCK ISLANDS. PMID- 17731770 TI - PREPATION OF TEACHERS OF SCIENCE AS CARRIED FORWARD IN THE MICHIGAN STATE NORMAL SCHOOL. PMID- 17731771 TI - THE FICTION OF THE AMERICAN HORSE AND THE TRUTH ON THIS DISPUTED POINT. PMID- 17731772 TI - ADAPTATION OF SEEDS TO FACILITATE GERMINATION. PMID- 17731773 TI - HEREDITY. PMID- 17731774 TI - WOMAN'S WORK FOR WAGES. PMID- 17731775 TI - A CONSIDERATION OF THE CLAIMS OF CHEMISTRY AS THE BASIS OF MODERN AGRICULTURE. PMID- 17731776 TI - Twins Among the Indians on Puget Sound. PMID- 17731777 TI - The Ancient Libyan Alphabet. PMID- 17731779 TI - A Large Southern Telescope. PMID- 17731778 TI - THE REAL MOTIONS OF THE FIXED STARS. PMID- 17731780 TI - Prevrention of Cholera Asiatica. PMID- 17731782 TI - Naltunne Tunne Measures. PMID- 17731783 TI - THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE THE METHOD OF SCIENCE. PMID- 17731781 TI - Omaha Arrow-Measure. PMID- 17731784 TI - THE FORMATION OF CARBOHYDRATES IN THE VEGETABLE KINGDOM. PMID- 17731785 TI - THE CARNEGIE INSTITUTION OF WASHINGTON. PMID- 17731787 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17731786 TI - THE AMERICAN MUSEUM OF NATURAL HISTORY. PMID- 17731788 TI - CARELESS CRITICISM. PMID- 17731789 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17731790 TI - NEW PHENOMENA OF ELECTRICAL DISCHARGE. PMID- 17731792 TI - THE AMERICAN PHYTOPATHOLOGICAL SOCIETY. PMID- 17731791 TI - JOINT MEETING OF MATHEMATICIANS AND ENGINEERS AT MINNEAPOLIS. PMID- 17731793 TI - This Week in SCIENCE. PMID- 17731795 TI - Supersymmetry. PMID- 17731794 TI - Increased use of renewable energy. PMID- 17731796 TI - More than one star. PMID- 17731797 TI - Sciecescope. PMID- 17731798 TI - BA Meets in Plymouth on Dinosaurs' Birthday: Dinosaurs' Changing Image. PMID- 17731799 TI - NASA's Fall Colors. PMID- 17731800 TI - Who is tops in brain research. PMID- 17731801 TI - Good yews. PMID- 17731803 TI - Getting a jump on gene transfer in Drosophila. PMID- 17731802 TI - Ozone mapper survives soviet coup. PMID- 17731804 TI - Astronomers get a whiff of methanol. PMID- 17731805 TI - Latest quarry in the quasar quest. PMID- 17731806 TI - When biotas meet: understanding biotic interchange. AB - When the barrier between biotas with long separate histories breaks down, species invade from one biota to the other. Studies of episodes of marine and terrestrial biotic interchange that have occurred during the last 20 million years show that large-scale extinction of species before the onset of interchange renders biotas especially prone to invasion. As environments and species are being exploited and eliminated on an ever increasing scale in the human-dominated biosphere, the geographical expansion of species from biotas in which evolution of high competitive, defensive, and reproductive abilities has proceeded the furthest will become more frequent. Historical events and interactions are essential ingredients for understanding the current and future structure and composition of the world's biota. PMID- 17731808 TI - Reversible decrease of gel-solvent friction. AB - The friction between water and the polymer network of a gel is found to decrease reversibly by three orders of magnitude and appears to diminish as the gel approaches a certain temperature at constant volume and network structure. PMID- 17731807 TI - Vapor-phase fabrication and properties of continuous-filament ceramic composites. AB - The continuous-filament ceramic composite is becoming recognized as necessary for new, high-temperature structural applications. Yet because of the susceptibility of the filaments to damage from traditional methods for the preparation of ceramics, vapor-phase infiltration has become the fabrication method of choice. The chemical vapor infiltration methods for producing these composites are now being studied in earnest, with the complexity of filament weaves and deposition chemistry being merged with standard heat and mass-transport relationships. Two of the most influential effects on the mechanical properties of these materials are the adhesion and frictional force between the fibers and the matrix, which can be controlled by a tailored interface coating. A variety of materials are available for producing these composites including carbide, nitride, boride, and oxide filaments and matrices. Silicon carbide-based materials are by far the most advanced and are already being used in aerospace applications. PMID- 17731809 TI - Synchrotron X-ray Diffraction from a Microscopic Single Crystal Under Pressure. AB - Metallic filaments with submicrometer diametere have been fabricated. Standard diffraction techniques with conventional x-ray sources were unsuccessful in identifying the structure of these materials. However, with the use of synchrotron radiation produced on a wiggler beam line, diffraction data were obtained in measurement periods as short as 10 milliseconds. Two cylindrical single crystals of bismuth were studied, each with a diameter of 0.22 +/- 0.02 micrometer. The volume of sample illuminated for these measurements was 0.38 cubic micrometer, less than 0.5 femtoliter. The crystals are grown in glass capillaries, and, because bismuth expands on solidification, they are under a residual hoop stress. The crystallographic data indicate the presence of a linear compressive strain of about 2 percent, which is assumed to be the result of a residual stress of about 2 gigapascals. PMID- 17731811 TI - Size and shape. PMID- 17731812 TI - Ocular chemistry. PMID- 17731810 TI - A member of our lineage. PMID- 17731813 TI - Correction. AB - The company name Stratagene was spelled incorrectly under the product heading ;;Still Video Gel Documenter'' in the 23 August issue (page 921). PMID- 17731814 TI - Products & materials. PMID- 17731815 TI - SCIENCE AND CIVILIZATION. PMID- 17731817 TI - THE AMERICAN SOCIETY OF AERONAUTIC ENGINEERS. PMID- 17731816 TI - INDUSTRIAL ACCIDENT STATISTICS. PMID- 17731818 TI - THE ORGANIZATION OF SCIENTIFIC RESEARCH IN GREAT BRITAIN. PMID- 17731820 TI - THE ATTITUDE OF THE STATE OF CALIFORNIA TOWARD SCIENTIFIC RESEARCH. PMID- 17731821 TI - A REPLY TO DR. LITTLE. PMID- 17731819 TI - PUBLIC HEALTH IN AMERICA. PMID- 17731822 TI - NOTES ON METEOROLOGY AND CLIMATOLOGY. PMID- 17731823 TI - ON THE REPRODUCTIVE AND HOST HABITS OF CUTEREBRA AND DERMATOBIA. PMID- 17731824 TI - RAPID METHOD OF COUNTING BACTERIA IN MILK. PMID- 17731825 TI - SCIENCE NEWS. PMID- 17731826 TI - THEORETICAL MECHANICS IN ENGINEERING SCHOOLS. PMID- 17731827 TI - PLANT QUARANTINE. PMID- 17731828 TI - OUR CONTEMPORARY RESEARCH "ACES". PMID- 17731829 TI - Sigma. PMID- 17731830 TI - OVERHEAD. PMID- 17731831 TI - PEDOGRAPHY. PMID- 17731832 TI - A CONVENIENT METHOD OF REDUCING DESICCATION IN SLANT CULTURES. PMID- 17731833 TI - A METHOD FOR DETECTING ACID-FAST BACTERIA IN THE SOIL. PMID- 17731834 TI - AN INTERPRETATION OF MASS CONJUGATION IN PARAMECIUM. PMID- 17731835 TI - SUSCEPTIBILITY OF WHITE MICE TO THE VIRUS OF YELLOW FEVER. PMID- 17731837 TI - This week in science. PMID- 17731836 TI - IS THERE A NEUROMOTOR APPARATUS IN DIPLODINIUM ECAUDATUM? PMID- 17731838 TI - Power from wind turbines. PMID- 17731839 TI - Response. PMID- 17731840 TI - Sciencescope. PMID- 17731841 TI - Mars Observer's Costly Solitude. PMID- 17731842 TI - The sounds of silence: chronology of despair. PMID- 17731843 TI - How observer became a ;billion-dollar mission'. PMID- 17731844 TI - NASA's Troubles Come in Droves. PMID- 17731845 TI - ;Greener' military pays off for civilian scientists. PMID- 17731846 TI - A different kind of grants program. PMID- 17731847 TI - Processing the new coke fiasco. PMID- 17731848 TI - Good chemistry at electronic conference. PMID- 17731849 TI - CFlood Uproots Transgenic Crop. PMID- 17731850 TI - State backs breast cancer research. PMID- 17731851 TI - Plastics that play on light. PMID- 17731852 TI - Evolution's Big Bang Gets Even More Explosive. PMID- 17731854 TI - Gran sasso: particle physics without mountains of money. PMID- 17731853 TI - Light microscopes get a sharper look. PMID- 17731855 TI - Rhenium-osmium evidence for regional mineralization in southwestern north america. AB - More than 40 base metal porphyry ore deposits in southwestern North America are associated with the Laramide orogeny (about 90 million to 50 million years ago). Rhenium-osmium dates on molybdenite, a rhenium-enriched sulfide common in many of the deposits, reveal that in individual deposits mineralization occurs near the final stages of magmatic activity irrespective of the time of inception, magnitude, or duration of magmatism. Deposits that differ widely in location and in the extent and timing of magmatism have nearly identical ages for mineralization. Rhenium-osmium-ages suggest that mineralization occurred during two distinct intervals from about 74 million to 70 million years ago and from 60 million to 55 million years ago. Most deposits that formed in the oldest interval are within the older Precambrian basement of northwestern Arizona, whereas the younger deposits are restricted to the younger Precambrian basement in southern Arizona and northern Mexico. Synchronous, widespread mineralization indicates that similar crust-mantle interaction occurred on a regional scale for ore deposits once thought to be the product of localized processes. PMID- 17731856 TI - Crystallization at Inorganic-organic Interfaces: Biominerals and Biomimetic Synthesis. AB - Crystallization is an important process in a wide range of scientific disciplines including chemistry, physics, biology, geology, and materials science. Recent investigations of biomineralization indicate that specific molecular interactions at inorganic-organic interfaces can result in the controlled nucleation and growth of inorganic crystals. Synthetic systems have highlighted the importance of electrostatic binding or association, geometric matching (epitaxis), and stereochemical correspondence in these recognition processes. Similarly, organic molecules in solution can influence the morphology of inorganic crystals if there is molecular complementarity at the crystal-additive interface. A biomimetic approach based on these principles could lead to the development of new strategies in the controlled synthesis of inorganic nanophases, the crystal engineering of bulk solids, and the assembly of organized composite and ceramic materials. PMID- 17731858 TI - Discovery of vapor deposits in the lunar regolith. AB - Lunar soils contain micrometer-sized mineral grains surrounded by thin amorphous rims. Similar features have been produced by exposure of pristine grains to a simulated solar wind, leading to the widespread belief that the amorphous rims result from radiation damage. Electron microscopy studies show, however, that the amorphous rims are compositionally distinct from their hosts and consist largely of vapor-deposited material generated by micrometeorite impacts into the lunar regolith. Vapor deposits slow the lunar erosion rate by solar wind sputtering, influence the optical properties of the lunar regolith, and may account for the presence of sodium and potassium in the lunar atmosphere. PMID- 17731857 TI - Cooperative formation of inorganic-organic interfaces in the synthesis of silicate mesostructures. AB - A model is presented to explain the formation and morphologies of surfactant silicate mesostructures. Three processes are identified: multidentate binding of silicate oligomers to the cationic surfactant, preferential silicate polymerization in the interface region, and charge density matching between the surfactant and the silicate. The model explains present experimental data, including the transformation between lamellar and hexagonal mesophases, and provides a guide for predicting conditions that favor the formation of lamellar, hexagonal, or cubic mesostructures. Model Q(230) proposed by Mariani and his co workers satisfactorily fits the x-ray data collected on the cubic mesostructure material. This model suggests that the silicate polymer forms a unique infinite silicate sheet sitting on the gyroid minimal surface and separating the surfactant molecules into two disconnected volumes. PMID- 17731859 TI - Lattice effect of strong electron correlation: implication for ferroelectricity and superconductivity. AB - Much theoretical work has been devoted to understanding the role of strong electron correlations in high-temperature superconductivity mainly through magnetic interactions, but the possible role of electron correlation in ferroelectricity of metal oxides has not received attention. Diagonalization of a simple many-body, tight-binding Hamiltonian shows that the electron-lattice interaction is dramatically enhanced in some cases by strong electron correlation because of deformation-induced charge transfer. This effect may be closely related to ferroelectricity and superconductivity in transition metal oxides. PMID- 17731860 TI - Molecular dynamics of adsorption and segregation from an alkane mixture. AB - Adsorption and segregation of n-hexadecane molecules from an equal by weight mixture of n-hexadecane and n-hexane to an Au(001) surface at 315 kelvin are studied with the use of molecular dynamics simulations. Preferential adsorption of n-hexadecane at the solid-to-liquid interface together with subsequent layer by-layer growth of an ordered, wetting interface were observed. The long chains penetrate and adsorb at the interfacial layer by means of a sequential segmental mechanism involving end-segment anchoring and displacive desorption of preadsorbed n-hexane molecules. PMID- 17731861 TI - A quasi-biennial oscillation signal in general circulation model simulations. AB - The quasi-biennial oscillation (QBO) is a free atmospheric mode that affects the equatorial lower stratosphere. With a quasi-regular frequency, the mean equatorial zonal wind alternates from easterly to westerly regimes. This oscillation is zonally symmetric about the equator, has its largest amplitude in the latitudinal band from 20 degrees S to 20 degrees N, and has a mean period of about 27 months. The QBO appears to originate in the momentum deposition produced by the damping in the stratosphere of equatorial waves excited by diabatic thermal processes in the troposphere. The results of three 10-year simulations obtained with three general circulation models are reported, all of which show the development in the stratosphere of a QBO signal with a period and a spatial propagating structure that are in good agreement with observations without any ad hoc parameterization of equatorial wave forcing. Although the amplitude of the oscillation in the simulations is still less than the observed value, the result is promising for the development of global climate models. PMID- 17731862 TI - Fabrication and magnetic properties of arrays of metallic nanowires. AB - Arrays of ferromagnetic nickel and cobalt nanowires have been fabricated by electrochemical deposition of the metals into templates with nanometer-sized pores prepared by nuclear track etching. These systems display distinctive characteristics because of their one-dimensional microstructure. The preferred magnetization direction is perpendicular to the film plane. Enhanced coercivities as high as 680 oersteds and remnant magnetization up to 90 percent have also been observed. PMID- 17731863 TI - Response. PMID- 17731865 TI - The physics of cold. PMID- 17731864 TI - Transformations and survivals. PMID- 17731866 TI - Vignettes: questions of standards. PMID- 17731867 TI - Products & materials. PMID- 17731868 TI - This week in science. PMID- 17731869 TI - Earth observations from space. PMID- 17731870 TI - Erratum. AB - In the Research News Article by Richard A. Kerr, "Does chaos permeate the solar system?" (14 Apr., p. 144), the orbital period of Mercury was misstated. The correct value is 88 days. PMID- 17731871 TI - Fusion reaction. PMID- 17731872 TI - Carbon-sequestering science: an alternative to "pesky electronics"? PMID- 17731873 TI - Faculty salaries. PMID- 17731874 TI - Here and there, a few bold experiments. PMID- 17731876 TI - Setting the record straight. PMID- 17731875 TI - Computers Make Slow Progress in Class: The high-tech transformation of education that some were predicting a few years ago has not happened. Experts battle over what role computers should play. PMID- 17731878 TI - Superconductivity: is the party over? PMID- 17731877 TI - Space telescope delayed (again). PMID- 17731879 TI - Giants Haven't Given Up on Superconductivity. PMID- 17731880 TI - ARCO Solar Sale Raises Concerns Over Potential Over Potential Technology Export. PMID- 17731882 TI - 1989 AAAS Philip Hauge Abelson Prize. PMID- 17731881 TI - Three-Dimensional Spherical Models of Convection in the Earth's Mantle. AB - Three-dimensional, spherical models of mantle convection in the earth reveal that upwelling cylindrical plumes and downwelling planar sheets are the primary features of mantle circulation. Thus, subduction zones and descending sheetlike slabs in the mantle are fundamental characteristics of thermal convection in a spherical shell and are not merely the consequences of the rigidity of the slabs, which are cooler than the surrounding mantle. Cylindrical mantle plumes that cause hotspots such as Hawaii are probably the only form of active upwelling and are therefore not just secondary convective currents separate from the large scale mantle circulation. Active sheetlike upwellings that could be associated with mid-ocean ridges did not develop in the model simulations, a result that is in agreement with evidence suggesting that ridges are passive phenomena resulting from the tearing of surface plates by the pull of descending slabs. PMID- 17731883 TI - Ice core evidence for extensive melting of the greenland ice sheet in the last interglacial. AB - Evidence from ice at the bottom of ice cores from the Canadian Arctic Islands and Camp Century and Dye-3 in Greenland suggests that the Greenland ice sheet melted extensively or completely during the last interglacial period more than 100 ka (thousand years ago), in contrast to earlier interpretations. The presence of dirt particles in the basal ice has previously been thought to indicate that the base of the ice sheets had melted and that the evidence for the time of original growth of these ice masses had been destroyed. However, the particles most likely blew onto the ice when the dimensions of the ice caps and ice sheets were much smaller. Ice texture, gas content, and other evidence also suggest that the basal ice at each drill site is superimposed ice, a type of ice typical of the early growth stages of an ice cap or ice sheet. If the present-day ice masses began their growth during the last interglacial, the ice sheet from the earlier (Illinoian) glacial period must have competely or largely melted during the early part of the same interglacial period. If such melting did occur, the 6-meter higher-than-present sea level during the Sangamon cannot be attributed to disintegration of the West Antarctic ice sheet, as has been suggested. PMID- 17731884 TI - Body and Brain. A Trophic Theory of Neural Connections. Dale Purves. Harvard University Press, Cambridge, MA, 1988. viii, 231 pp., illus. $35. PMID- 17731885 TI - Critical Observations versus Physical Models for Close Binary Systems. Kam-Ching Leung, Ed. Gordon and Breach, New York, 1988. xvi, 472 pp., illus. $95. From a colloquium, Beijing, China, Nov. 1985. PMID- 17731886 TI - Interleukin 2. Kendall A. Smith, Ed. Academic Press, San Diego, CA, 1988. xxii, 311 pp., illus. $69. PMID- 17731888 TI - Products & materials. PMID- 17731889 TI - Complete creature. PMID- 17731890 TI - Spectrometry service. PMID- 17731892 TI - Letters to the editor. PMID- 17731891 TI - Wesleyan's Science. PMID- 17731893 TI - Letters to the editor. PMID- 17731894 TI - Law and science. PMID- 17731895 TI - Aaas symposium volumes. PMID- 17731896 TI - Kilauea volcano: the 1967-68 summit eruption. PMID- 17731897 TI - Language universals: a research frontier. PMID- 17731898 TI - NSF: McElroy Seeks to Impart Political Headway to Agency. PMID- 17731900 TI - Panel on oil spills warns of more. PMID- 17731902 TI - Britain: new emphasis on industrial research. PMID- 17731903 TI - Campus unrest: confrontation increasingly means litigation. PMID- 17731901 TI - M.I.T. "I" lab changing direction. PMID- 17731904 TI - Salvador Luria Excluded by HEW. PMID- 17731906 TI - Glacier oxygen-18 content and pleistocene ocean temperatures. AB - The mean oxygen-18 content of continental ice sheets during the last glacial maximum is estimated to deltaO(18)=-30 per mille or less, and the consequent change in the isotopic composition of the oceans at that time to 1.2 per mille or more. This means that at least 70 percent of the oxygen-18 variations found in shells of planktonic foraminifera from deep-sea cores between times of glacial maximums and minimums are due to isotopic changes in ocean water, and at most 30 percent to changes in ocean surface temperature. Hence, Emiliani's "paleotemperature" curve rather depicts the amount of ice on the continents in excess of that present today. In this sense it may be renamed a "paleoglaciation" curve. PMID- 17731905 TI - Infrared Absorptions near Three Microns Recorded over the Polar Cap of Mars. AB - During the Mariner 7 flyby of Mars, the infrared spectrometer recorded distinct, sharp absorption. near 3020 and 3300 reciprocal centimeters between 61 degrees S and 80 degrees S. at the edge of the southern polar cap, with maximum optical density near 68 degrees S and 341 degrees E. These hands, which match in frequency the v(3) bands of methane and ammonia, can be associated with previously unreported spectral features of solid carbon dioxide exceeding 1 millimeter in thickness. Possible reasons for the geographic localization are discussed. PMID- 17731907 TI - Dredged trachyte and basalt from kodiak seamount and the adjacent aleutian trench, alaska. AB - Blocky fragments of aegirine-augite trachyte (with accompanying icerafted gravels.) were recovered from the upper slopes of Kodiak Seamount in several dredge hauls. An alkali basalt pillow segment was also dredged from a moatlike depression, at a depth of 5000 meters, near the west base of the seamount. These retrievals confirm the volcanic origin of Kodiak Seamount and further support the view of Engel, Engel, and Havens that the higher elevations of seamounts are composed of alkali basalts or related variants. PMID- 17731908 TI - Flower of Tetraplasandra gymnocarpa Hypogyny with Epigynous Ancestry. AB - Comparative herbarium studies, floral anatomy, and distributional data show that Tetraplasandra gymnocarpa, an araliad with hypogynous flowers, evolved in Hawaii from ancestors with epigynous flowers. Suggested causes for this reversal of a well-known evolutionary trend are (i) isolation of the ancestors from flowereating predators and (ii) selection for increased outcrossing. PMID- 17731909 TI - Lunar thermal anomalies: magnetic phase transitions on the lunar surface? PMID- 17731910 TI - Rational use of water. PMID- 17731912 TI - ON THE INCREASING IMPORTANCE OF INORGANIC CHEMISTRY. PMID- 17731911 TI - REFORM IN MEDICAL EDUCATION. PMID- 17731913 TI - THE TAILLESS BATRACHIANS OF EUROPE. PMID- 17731915 TI - PROBLEMS OF PHYSIOGRAPHY CONCERNING SALINITY AND TEMPERATURE OF THE PACIFIC OCEAN. PMID- 17731914 TI - SKELETON LEAVES. PMID- 17731916 TI - THE STORING OF PAMPHLETS. PMID- 17731918 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17731917 TI - NOTES ON INORGANIC CHEMISTRY. PMID- 17731919 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17731920 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17731921 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17731923 TI - ZOOLOGICAL BIBLIOGRAPHY. PMID- 17731922 TI - DISCUSSION AND CORRESPONDENCE. PMID- 17731924 TI - LEHMAN AND HANSEN 'ON THE TELEPATHIC PROBLEM.'. PMID- 17731925 TI - SCIENTIFIC JOURNALS. PMID- 17731926 TI - Low Temperature Physics. PMID- 17731928 TI - Volatile Silica Affecting Plant Ash Analyses. PMID- 17731927 TI - Meetings & Conferences. PMID- 17731929 TI - The Function of the Cups of Polyporus conchifer. PMID- 17731930 TI - Crucial Experiment. PMID- 17731931 TI - Wave-Riding Dolphins: How Do They Do It?: At present only the dolphin knows the answer to this free-for-all in hydrodynamics. PMID- 17731932 TI - The Forgotten Man: Sir John Lubbock: His contributions to zoology and his liberal record as a member of Parliament ought to be remembered. PMID- 17731933 TI - Public Interest in Science News: Two surveys show a direct relationship between science education and assimilation of the news. PMID- 17731934 TI - Explanation and Prediction in Economics: The basic statements of economics may serve to explain the past but not to predict the future. PMID- 17731935 TI - American Science between 1780 and 1830: The exploration and industrialization of the new nation led to advances in natural science and technology. PMID- 17731936 TI - Geology, Geologists, and the AAAS: The inclusive association has an important role to play in a time of increasing specialization in science. PMID- 17731937 TI - Transliteration of Russian. AB - The objective of any system of transliteration is obviously to convey to the reader as closely as possible the phonetic value of the transliterated material. Barring phonetic transcriptions, this objective is doubtless best accomplished when (i) minimum use is made of extra marks and extra letter combinations that of necessity are arbitrary, unclear, and confusing to many readers, and when, of course (ii), there is only one uniform system and not a variety of varying ones. A detailed analysis reveals that present-day practices of transliterating Russian into English by no means conform to these desiderata, but that they could readily be made to do so. With only two extra letter combinations, zh for and kh for x, and a single and a double apostrophe for the "soft" and "hard" marks, a very close approximation of Russian phonology may be attained through a discriminating use of English as is. A complete and uniform transliteration of Russian into English, including the noncontroversial letters, is shown in Table 1. PMID- 17731938 TI - News of Science: House Science and Space Committee Holds Hearings to Establish the Scope of Its Responsibilities. PMID- 17731939 TI - Index of Books Reviewed in Science 25 April 1958 through 17 April 1959. PMID- 17731940 TI - Keynes' Model. PMID- 17731941 TI - Keynes' Model. PMID- 17731942 TI - Who Should Teach English? PMID- 17731944 TI - Source of Fallout. PMID- 17731946 TI - COMMENT AND CRITICISM. PMID- 17731945 TI - German Scientists and Atom Bomb. PMID- 17731947 TI - POETRY AND MUSIC OF SOME NORTH AMERICAN TRIBES. PMID- 17731949 TI - EXPLORATION AND TRAVEL. PMID- 17731948 TI - LONDON LETTER. PMID- 17731950 TI - Mole-lore. PMID- 17731952 TI - Winds in Denver. PMID- 17731951 TI - Geographical centre of the United States. PMID- 17731954 TI - Some hardy buds. PMID- 17731955 TI - Death of Dr. Albert Kellogg. PMID- 17731953 TI - On tiptoe. PMID- 17731957 TI - Snake and snake-like mounds in Minnesota. PMID- 17731958 TI - Arctic Botanical Research. PMID- 17731956 TI - The barometer during thunder-storms. PMID- 17731959 TI - The Problem of Antiscientific Trends Today. PMID- 17731960 TI - Physiology of an Infrared Receptor: The Facial Pit of Pit Vipers. PMID- 17731961 TI - Isomorphism of Terramycin and Aureomycin Hydrochlorides. PMID- 17731962 TI - A Virus Possibly Related to the Psittacosis-Lymphogranuloma-Pneumonitis Group Causing a Pneumonia in Sheep. PMID- 17731963 TI - Some Aspects of the Phenomenon of Coacervation. PMID- 17731964 TI - Effect of Heat on the Properties of Urea at its Melting Point. PMID- 17731965 TI - Sodium Pentobarbital Anesthesia and Mortality from X-Radiation in C57 Black Mice. PMID- 17731966 TI - Polarizing Forces of the Muscarinic Moiety. PMID- 17731968 TI - Reservist Reaction. PMID- 17731967 TI - Hypothesis of the Biological Action of Radiation. PMID- 17731969 TI - Flash in Photomicrography. PMID- 17731970 TI - A Citizen's Duty. PMID- 17731971 TI - Distilled Water from Boiler Steam. PMID- 17731972 TI - A Simple Pipetting Device. PMID- 17731973 TI - Erratum. AB - In Table 1 of the report "Monoclonal antibody to Thy-1 enhances regeneration of processes by rat retinal ganglion cells in culture" by D. Leifer et al. (20 Apr., p. 303), the unit of measurement, micrometers, was omitted in the third column, "Mean length of processes per cell." PMID- 17731974 TI - Research sites. PMID- 17731975 TI - Research sites. PMID- 17731976 TI - The minority student challenge. PMID- 17731977 TI - Common elements and interconnections. AB - The major concepts addressed in this article are the synergistic nature of science, engineering, and technology; the benefits and burdens of technology; the resolution of societal issues; and the roles of scientists and engineers in the resolution of societal issues. PMID- 17731978 TI - Science and technology in a world transformed. AB - In this era of rapid, far-reaching transformation, our way of life is in many respects a novelty for our species. Opportunities arising from profoundly enhanced capabilities in science and technology are felt in every sphere of life from health to communication, yet each advance has side effects that take time to appear. Grave institutional inadequacies are manifested in the prevalence of totalitarian governments, proliferation of devastating weapons, failure of educational institutions to prepare most people for the modern world, failure to use what we know to prevent damage to a large proportion of the world's children; and the weakness of international institutions to deal with global interdependence in the face of persistent ethnocentrism and prejudice. The American scientific community can usefully become more deeply engaged with these great problems. PMID- 17731979 TI - Uranium power and horizontal proliferation of nuclear weapons. AB - Only a few nonnuclear weapons states with uranium-fueled power plants have kept the weapons option open, and none has evidenced activities intended for diverting fissionable material from its civilian system. Analysis of alternative strategies shows that acquisition of nuclear weapons material would probably depend on military production facilities rather than diversion. Horizontal proliferation is primarily a political issue and is related only marginally to uranium power development. Restrictions of the Nuclear Non-Proliferation Act on the supply of equipment and fuel by the United States appear to have induced, in some nonnuclear weapons states, the building of small-scale facilities that can be modified for production of weapons material. More attention should be given to the international political, economic, and military factors that persuade such states to abjure nuclear weapons. PMID- 17731980 TI - Variations in the rotation of the Earth. AB - Variations in the earth's rotation (UT1) and length of day have been tracked at the submillisecond level by astronomical radio interferometry and laser ranging to the LAGEOS satellite. Three years of regular measurements reveal complex patterns of variations including UT1 fluctuations as large as 5 milliseconds in a few weeks. Comparison of the observed changes in length of day with variations in the global atmospheric angular momentum indicates that the dominant cause of changes in the earth's spin rate, on time scales from a week to several years, is the exchange of angular momentum between the atmosphere and the mantle. The unusually intense El Nino of 1982-1983 was marked by a strong peak in the length of day. PMID- 17731981 TI - Europe to boost biotechnology? PMID- 17731982 TI - White House Freezes Synfuels Program: The Secretary of Energy unveils a plan to cut subsidy funds by two-thirds and eliminate uncompetitive ventures. PMID- 17731983 TI - Third world academy looks for funds. PMID- 17731984 TI - China-U.S. Science Cooperation Blooming: In the cause of modernization, Chinese undertake exchanges of students, scholars, and joint research. PMID- 17731985 TI - No Genome Barriers to Promiscuous DNA: The movement of DNA sequences between mitochondrial, chloroplast and nuclear genomes is even more prolific than had been expected. PMID- 17731986 TI - New Light on Dark Matter?: It fills the universe, it is utterly invisible, and it may not even exist; meanwhile, the hypotheses are getting more exotic. PMID- 17731987 TI - NMR with No Magnetic Field: Zero-field NMR makes it possible to obtain high quality spectra from powders and polycrystalline solids. PMID- 17731988 TI - Long Valley Is on Low Simmer for Now: The rumbling and bulging of the ground near Mammoth Lakes, California, has subsided but not halted as two other calderas threaten volcanic eruptions. PMID- 17731989 TI - New data guide available. PMID- 17731990 TI - Truman and science. PMID- 17731991 TI - Interciencia focuses on plant resources and latin biotechnology network. PMID- 17731992 TI - Inductive primatology: primate social relationships. PMID- 17731993 TI - Successors to newton: optics after newton. PMID- 17731994 TI - European prehistory: the prehistory of germanic europe. PMID- 17731995 TI - Outside Views of Science: Science under Scrutiny. PMID- 17731996 TI - Modeling long-term fluctuations in fish stocks. PMID- 17731997 TI - The vega particulate shell: comets or asteroids? AB - The Infrared Astronomical Satellite (IRAS) science team has discovered a shell of particulate material around the star Vega. At the mean distance and temperature of the shell, the expected condensation products from a protostellar nebula would be dominated by frozen volatiles, in particular water ice. It is not possible to discriminate between dirty ice and silicate materials in the Vega shell on the basis of the IRAS data. The Vega shell is probably a ring of cometary bodies with an estimated minimum mass of 15 earth masses, analogous to one that has been hypothesized for the solar system. A possible hot inner shell around Vega may be an asteroid-like belt of material a few astronomical units from the star. PMID- 17731998 TI - Time-domain reflectometry: simultaneous measurement of soil water content and electrical conductivity with a single probe. AB - Two parallel metallic rods were used as a wave guide to measure the dielectric constant and electrical conductivity of soils having different electrical conductivities but the same water content. Measurements showed that the two parameters were sufficiently independent to permit simultaneous determinations of water content and bulk electrical conductivity. PMID- 17731999 TI - Nautilus growth and longevity: evidence from marked and recaptured animals. AB - Study of Nautilus belauensis i its natural habitat in Palau, West Caroline Islands, shows that growth is slow (0.1 millimeter of shell per day on the average) and decreases as maturity is approached and that individuals may live at least 4 years beyond maturity. Age estimates for seven animals marked and recaptured between 45 and 355 days after release range from 14.5 to 17.2 years. These data indicate that the life-span of Nautilus may exceed 20 years and that its life strategy is very different from that of other living cephalopods. PMID- 17732000 TI - Transient expression of homologous genes in Drosophila cells. AB - A cloned Drosophila heat shock protein 22 gene was transfected into two independently established Drosophila cell lines. Each line carried a different heat shock protein 22 allele, distinguishable by electrophoresis of the protein. The transfected gene was not expressed at 25 degrees C but could be induced at 36 degrees C. In one line, two heat shock protein 22 electromorphs were synthesized. PMID- 17732001 TI - COSEPP Study Under Way. PMID- 17732002 TI - SECTION B--PHYSICS. I. PMID- 17732003 TI - THE CARNEGIE INSTITUTION OF WASHINGTON. PMID- 17732004 TI - SCHAEBERLE, BECKER AND THE COOLING EARTH. PMID- 17732005 TI - THE REDISCOVERY OF A LOST ART AND A FEW NOTES ON THE THEORY OF THE VIOLIN. PMID- 17732007 TI - THE CARNEGIE FOUNDATION FOR THE ADVANCEMENT OF TEACHING. PMID- 17732006 TI - MONTHLY WEATHER REVIEW. PMID- 17732008 TI - Lyman J. Briggs. PMID- 17732010 TI - The Occurrence of an Unusually High-Level Radioactive Rainout in the Area of Troy, N. Y. PMID- 17732009 TI - Meetings & Conferences. PMID- 17732011 TI - Equatorial Undercurrent in Pacific Ocean Revealed by New Methods. PMID- 17732012 TI - Diffusion Lines in Silver Chromate Gelatin. PMID- 17732013 TI - A Rapid Quantitative Chemical Procedure for Analysis for Niobium. PMID- 17732014 TI - Another Attempt at Classifying American Scientists. PMID- 17732015 TI - Another Cooperative Multiple-Choice Apparatus. PMID- 17732016 TI - Paleocene Ostracoda from Outcrops in Maryland. PMID- 17732017 TI - Computations of Total Sediment Discharge, Niobrara River near Cody, Nebraska. PMID- 17732019 TI - The Geology of Glacier National Park and Vicinity in Montana. PMID- 17732018 TI - Rejoinder. PMID- 17732020 TI - A New Method for the Production of Autoradiographs. PMID- 17732021 TI - Stromatolite Classification in the Belt Series. PMID- 17732022 TI - This week in science. PMID- 17732023 TI - A changing china. PMID- 17732024 TI - Erratum. AB - In the third paragraph of the briefing "New funds for AIDS drug centers" by Deborah M. Barnes (News & Comment, 25 July, p. 414), the name of the drug foscarnet was spelled incorrectly. PMID- 17732025 TI - Diet and cancer. PMID- 17732026 TI - Existence of cannibalism. PMID- 17732027 TI - Existence of cannibalism. PMID- 17732028 TI - Existence of cannibalism. PMID- 17732029 TI - Dissenters see for-profits as threat to public interest. PMID- 17732030 TI - France Weighs Benefits, Risks of Nuclear Gamble: Unswerving political commitment, national pride, and firm state control of all levels of debate help explain the rapid growth of France's nuclear power program. PMID- 17732031 TI - Nuclear waste program hits senate roadblock. PMID- 17732032 TI - OTA Enters Inflamed Debate on Ocean Incineration. PMID- 17732034 TI - Tokamak sets records in temperature and confinement. PMID- 17732033 TI - Phase Transition Seen at Alloy Grain Boundary: Cornell researchers have evidence for the proposition that gold in an iron alloy bicrystal preferentially collects at the grain boundary and triggers a change in its structure. PMID- 17732035 TI - Prime tests and keeping proofs secret. AB - Stanford, California. On 29 July through 2 August, a group of computer scientists, mathematical physicists, and mathematicians met at Stanford University for a conference on Mathematics and Computers. It was a varied meeting the talks ranged from the mathematics of chaos to a talk by the peripatetic Hungarian mathematician Paul Erdos on number theory problems that might be interesting to work on. In addition, software vendors set up shop, inviting investigators to bring their problems and try them on different systems. On the last day of the conference, when the talks were in the field of computational complexity-the difficulty of doing certain computer calculations-two new computer science tricks were presented and are recounted here. PMID- 17732036 TI - Mars is getting wetter and wetter. PMID- 17732037 TI - Ancient river system across Africa proposed. PMID- 17732038 TI - Eruption of the nevado del ruiz volcano, Colombia, on 13 november 1985: tephra fall and lahars. AB - A small Plinian eruption of the Nevado del Ruiz volcano in Colombia ejected 3.5 x 10(10) kilograms of mixed dacite and andesite tephra on 13 November 1985, with a maximum column height of 31 kilometers above sea level. Small pyroclastic flows and surges, generated during the initial stage of the eruption, caused surface melting of approximately 10% of the volcano's ice cap, leading to meltwater floods. The erosive floods incorporated soils and loose sediments from the volcano's flanks and developed into lahars, which claimed at least 25,000 lives. PMID- 17732039 TI - Eruption of the nevado del ruiz volcano, Colombia, on 13 november 1985: gas flux and fluid geochemistry. AB - The 13 November 1985 eruption of Nevado del Ruiz volcano, in Colombia, released a small volume of pyroclastic material and a disproportionately large volume of volcanic gas. Before the eruption, summit fumarole gases became less water-rich, and the sulfur/chlorine ratio increased. Remote measurements of sulfur dioxide flux after the eruption indicated active degassing at levels associated with eruptive or inter-eruptive stages of other volcanoes. Thermal water analyses revealed increases in magnesium, calcium, and potassium and an increase in the magnesium/chlorine ratio, suggesting that these elements may have been leached from new magma. Ash leachate data showed sulfate and chloride concentrations and ratios that would be expected for the late stages ofa major Plinian eruption. Water from the lahar contained high concentrations of sulfate and had a sulfur/chlorine ratio of 4.67, suggesting that water ejected from the crater lake and turbulent mixing of pyroclasts and glacial ice triggered the lahar. Microprobe analyses of pumice from this eruption and the most recent previous event showed similar mixed andesites. The uniform composition of the pumices and the unusually high ratio of gas to magma suggest that, although a new batch of magma triggered this eruption, the pumice that erupted may actually be old. Large volumes of new magma and glacial ice make the volcano dangerous and should stimulate development of an integrated long-term monitoring program to include Tolima volcano, 25 kilometers to the south. PMID- 17732040 TI - Conodont survival and low iridium abundances across the permian-triassic boundary in South china. AB - The Permian-Triassic sedimentary sequence of China includes one of the most complete and fossiliferous Paleozoic-Mesozoic boundaries known. Closely spaced sampling across the boundary, which is an important extinction event for most organisms, has produced good conodont faunas that show little diversity change. A drop in conodont abundance is the only apparent response to the extinction event. A low concentration of iridium in the boundary clay (0.002 part per billion +/-20 percent), as well as in samples immediately below and above, that range from 0.004 to 0.034 part per billion do not support the proposal of an extraterrestrial impact event at this boundary in China. PMID- 17732042 TI - Approaches to environmental regulation: controlling chemicals and loading the dice. PMID- 17732041 TI - Response: calmodulin, cyclophilin, and cyclosporin a. PMID- 17732043 TI - A biological system: the sea urchin embryo. PMID- 17732045 TI - Some other books of interest: biology of new world microtus. PMID- 17732044 TI - Invertebrate phylogeny: the origins and relationships of lower invertebrates. PMID- 17732046 TI - Copper chemistry: biological and inorganic copper chemistry. PMID- 17732047 TI - Some other books of interest: response and stability. PMID- 17732048 TI - Some other books of interest: predator-prey relationships. PMID- 17732049 TI - FUNDAMENTAL UNITS IN BIOLOGY. PMID- 17732050 TI - ANOTHER NOTE ON SCIENTIFIC WRITING. PMID- 17732051 TI - OPINIONS RENDERED BY THE INTERNATIONAL COMMISSION ON ZOOLOGICAL NOMENCLATURE. PMID- 17732052 TI - THE APPROXIMATE CONNECTION OF BOILING POINTS FOR VARIATION IN BAROMETRIC PRESSURE. PMID- 17732054 TI - VITAMIN C IN PASTEURIZED MILK. PMID- 17732053 TI - MEETING OF THE EXECUTIVE COMMITTEE. PMID- 17732055 TI - PERMANENT PRESERVATION OF SMALL ZOOLOGICAL SPECIMENS. PMID- 17732056 TI - DETERMINATION OF THE VISUAL POWER OF EACH EYE IN ANIMALS. PMID- 17732057 TI - RESTLESSNESS AND MORBID HUNGER IN MAN. PMID- 17732058 TI - LABELING MUSEUM SPECIMENS AND LABORATORY EQUIPMENT. PMID- 17732059 TI - SCIENTIFIC RESEARCH, THE HOPE OF THE SOUTH. PMID- 17732060 TI - FIELD PROGRAM OF THE CANADIAN BUREAU OF GEOLOGY AND TOPOGRAPHY. PMID- 17732061 TI - THE ILLINOIS-INDIANA SECTION OF THE SOCIETY FOR THE PROMOTION OF ENGINEERING EDUCATION. PMID- 17732062 TI - THE COOK OBSERVATORY. PMID- 17732063 TI - OFFICERS OF THE AMERICAN INSTITUTE OF ELECTRICAL ENGINEERS. PMID- 17732065 TI - COLLECTING SUBTROPICAL PLANTS AND ANIMALS IN NORTHERN OHIO. PMID- 17732066 TI - RESISTANCE TO SULFANILYL DERIVATIVES IN VITRO AND IN VIVO. PMID- 17732064 TI - A POSSIBLE EXPLANATION OF DEEP-FOCUS QUAKES. PMID- 17732067 TI - COLLECTION OF UNORTHODOX CURIOSA. PMID- 17732068 TI - THE NEW YORK STATE GEOLOGICAL ASSOCIATION. PMID- 17732069 TI - THE NEW HAMPSHIRE ACADEMY OF SCIENCE. PMID- 17732070 TI - THE ACTION OF TYPE-SPECIFIC ANTIBODY UPON THE PULMONARY LESION OF EXPERIMENTAL PNEUMOCOCCAL PNEUMONIA. PMID- 17732071 TI - ALCOHOLIC FERMENTATION BY FUSARIA JUICE OBTAINED WITH A WET CRUSHING MILL. PMID- 17732072 TI - THE USE OF PLASTIC AS A SUBSTITUTE FOR COVER GLASSES. PMID- 17732073 TI - GROWTH RESPONSE OF PLANTS TO RIBOFLAVIN AND ASCORBIC ACID. PMID- 17732074 TI - ERRATIC POTENTIALS OF ELECTRODES SEALED IN GLASS TUBING. PMID- 17732075 TI - The Role of Lemmings at Point Barrow, Alaska. PMID- 17732076 TI - Catalytic Effect of the Chromic Ion in the Barker Method for Protein-bound Iodine Determination. PMID- 17732078 TI - Temperature and Man. PMID- 17732077 TI - Temperature and Man. PMID- 17732079 TI - SCIENCE NEWS. PMID- 17732080 TI - INTRODUCTORY ADDRESSES. PMID- 17732082 TI - OBITUARY. PMID- 17732081 TI - THE SOCIAL EFFECTS OF MODERN SCIENCE. PMID- 17732083 TI - THE OUACHITA PROJECT. PMID- 17732084 TI - INFECTION OF THE CLOACA WITH THE VIRUS OF INFECTIOUS BRONCHITIS. PMID- 17732085 TI - A NEW METEORITE FROM THE BLACK HILLS. PMID- 17732087 TI - A METHOD FOR THE DETERMINATION OF THE VELOCITY OF SOUND IN SOLIDS. PMID- 17732086 TI - ZOOLOGICAL NOMENCLATURE. PMID- 17732088 TI - CORRUGATED RUBBER TAMBOUR DIAPHRAGMS. PMID- 17732090 TI - This week in science. PMID- 17732089 TI - SEXUAL VARIATIONS IN THE PELVIS. PMID- 17732091 TI - Science and everyday life. PMID- 17732093 TI - Ecological research. PMID- 17732092 TI - Ecological research. PMID- 17732095 TI - Response. PMID- 17732094 TI - Ecological research. PMID- 17732096 TI - Ecological research. PMID- 17732098 TI - Biologist Takes Seat as U.K.'s Top Science Adviser. PMID- 17732097 TI - NASA Mission Gets Down to Earth. PMID- 17732099 TI - Incentives offer hope for habitat. PMID- 17732101 TI - Earth's Surface May Move Itself. PMID- 17732100 TI - Panel Suggests Fewer NSF Centers. PMID- 17732102 TI - ... But did deeper forces act to uplift the andes? PMID- 17732103 TI - Physicists polish one model while looking to the next. AB - BRUSSELS, BELGIUM-High-energy physicists' current explanation for the behavior of subatomic particles and forces, known as the Standard Model, is doing just fine. That was the take-home message for the 800 delegates who gathered here from 27 July to 2 August for the International Europhysics Conference on High-Energy Physics. "Mainly this was a conference of consolidation, steady progress, many very beautiful and detailed results," Christopher Llewellyn Smith, director general of CERN, the European particle physics laboratory, told Science. But while a multitude of presentations described ever more accurate tests and confirmations of the model, physicists also discussed hints that a whole new range of phenomena beyond the Standard Model is lurking just above the energies of current accelerators-and within range of the next generation of experiments. PMID- 17732105 TI - California Volcano's Slow Fizz a Warning? PMID- 17732104 TI - Casting a wide net for cosmic rays. PMID- 17732106 TI - Sperm protein gets specific. PMID- 17732107 TI - The oldest supernova. PMID- 17732108 TI - Building a scientifically sound policy for protecting endangered species. PMID- 17732109 TI - Templating of mesoporous molecular sieves by nonionic polyethylene oxide surfactants. AB - Mesoporous silica molecular sieves have been prepared by the hydrolysis of tetraethylorthosilicate in the presence of low-cost, nontoxic, and biodegradable polyethylene oxide (PEO) surfactants, which act as the structure-directing (templating) agents. This nonionic, surfactant-neutral, inorganic-precursor templating pathway to mesostructures uses hydrogen bonding interactions between the hydrophilic surfaces of flexible rod- or worm-like micelles and Si(OC(2)H(5))(4-x)(OH)(x) hydrolysis products to assemble an inorganic oxide framework. Disordered channel structures with uniform diameters ranging from 2.0 to 5.8 nanometers have been obtained by varying the size and structure of the surfactant molecules. Metal-substituted silica and pure alumina mesostructures have also been prepared by the hydrolysis of the corresponding alkoxides in the presence of PEO surfactants. These results suggest that nonionic templating may provide a general pathway for the preparation of mesoporous oxides. PMID- 17732110 TI - Multiscaling properties of large-scale structure in the universe. AB - The large-scale distribution of galaxies and galaxy clusters in the universe can be described in the mathematical language of multifractal sets. A particularly significant aspect of this description is that it furnishes a natural explanation for the observed differences in clustering properties of objects of different density in terms of multiscaling, the generic consequence of the application of a local density threshold to a multifractal set. The multiscaling hypothesis suggests ways of improving upon the traditional statistical measures of clustering pattern (correlation functions) and exploring further the connection between clustering pattern and dynamics. PMID- 17732111 TI - Biological Controls on Coral Sr/Ca and dgr18O Reconstructions of Sea Surface Temperatures. AB - Coral strontium/calcium ratios have been used to infer that the tropical sea surface temperature (SST) cooled by as much as 6 degrees C during the last glacial maximum. In contrast, little or no change has been inferred from other marine-based proxy records. Experimental studies of the effect of growth rate and the magnitude of intraspecific differences indicate that biological controls on coral skeletal strontium/calcium uptake have been underestimated. These results call into question the reliability of strontium/calcium-based SST reconstructions. PMID- 17732112 TI - Energetics, patterns of interaction strengths, and stability in real ecosystems. AB - Ecologists have long been studying stability in ecosystems by looking at the structuring and the strengths of trophic interactions in community food webs. In a series of real food webs from native and agricultural soils, the strengths of the interactions were found to be patterned in a way that is important to ecosystem stability. The patterning consisted of the simultaneous occurrence of strong "top down" effects at lower trophic levels and strong "bottom up" effects at higher trophic levels. As the patterning resulted directly from the energetic organization of the food webs, the results show that energetics and community structure govern ecosystem stability by imposing stabilizing patterns of interaction strengths. PMID- 17732113 TI - Endoreduplication in maize endosperm: involvement of m phase--promoting factor inhibition and induction of s phase--related kinases. AB - Endoreduplication is an endonuclear chromosome duplication that occurs in the absence of mitosis and in Zea mays (L.) is required for endosperm development. Induction of DNA synthesis during early stages of endosperm development is maintained by increasing the amount and activity of S phase-related protein kinases, which was demonstrated here by their ability to interact with human E2F or with the adenovirus E1A proteins. In addition it was shown that endoreduplicated endosperm cells contain an inhibitor that suppresses the activity of the M phase-promoting factor (MPF). These results demonstrate that in maize endosperm, endoreduplication proceeds as a result of two events, inhibition of MPF and induction of S phase-related protein kinases. PMID- 17732114 TI - Lunar phase influence on global temperatures. PMID- 17732115 TI - Response. PMID- 17732117 TI - Vignettes: technological advance. PMID- 17732116 TI - Lunar phase influence on global temperatures. PMID- 17732118 TI - Other books of interest. PMID- 17732119 TI - Other books of interest. PMID- 17732120 TI - Products & materials. PMID- 17732121 TI - COOPERATION BETWEEN ZOOLOGICAL LABORATORIES AND THE GOVERNMENT BUREAUS. PMID- 17732122 TI - THE HISTORY OF POISON GASES. PMID- 17732123 TI - DUTY FREE SUPPLIES. PMID- 17732124 TI - ERRONEOUS GENERIC DETERMINATIONS OF BEES. PMID- 17732125 TI - GEOMORPHOLOGY. PMID- 17732126 TI - "A WAVE OF LIFE". PMID- 17732127 TI - ANTHROPOLOGICAL RESEARCH. PMID- 17732128 TI - EGG-WEIGHT AS A CRITERION OF NUMERICAL PRODUCTION IN THE DOMESTIC FOWL. PMID- 17732130 TI - THE BULLETIN OF THE AMERICAN MUSEUM OF NATURAL HISTORY. PMID- 17732129 TI - SHOULD LATIN AND GREEK BE REQUIRED FOR THE DEGREE OF BACHELOR OF ARTS? PMID- 17732131 TI - THE VERTEBRAL FORMULA IN DIPLODOCUS, MARSH. PMID- 17732132 TI - UNVEILING OF THE HUXLEY MEMORIAL. PMID- 17732133 TI - A NATIONAL LIBRARY AND MUSEUM OF THE HISTORY OF CHEMISTRY AND COGNATE ARTS AND SCIENCES. PMID- 17732134 TI - CEDAR COLLARS OF THE NORTH PACIFIC COAST INDIANS. PMID- 17732135 TI - THE GRAPHOPHONE AS AN AUXILIARY ASTRONOMICAL INSTRUMENT. A SUGGESTION. PMID- 17732136 TI - A CORRECTION. PMID- 17732137 TI - HIGHHOLE COURTSHIP AGAIN. PMID- 17732139 TI - DIETARY STUDIES OF UNIVERSITY BOAT CREWS. PMID- 17732138 TI - APPLIED SCIENCE IN MUNICIPAL WORK. PMID- 17732140 TI - 'ARROWPOINTS, SPEARHEADS AND KNIVES OF PREHISTORIC TIMES.'. PMID- 17732141 TI - LAKE LABORATORY OF THE OHIO STATE UNIVERSITY. PMID- 17732142 TI - RADIOACTIVITY AND THE AGE OF THE EARTH. PMID- 17732143 TI - CHEMISTRY IN THE FIELD OF MICROBIOLOGY. PMID- 17732144 TI - THE ORIGIN OF OIL POOLS. PMID- 17732145 TI - FOSSIL REMAINS IN THE ARCHAEAN ROCKS. PMID- 17732146 TI - INSECT WARFARE. PMID- 17732147 TI - EXPERIMENTUM PERICULOSUM; JUDICIUM DIFFICILE. PMID- 17732148 TI - THE CAUSES AND PREDICTION OF EARTHQUAKES. PMID- 17732149 TI - FIRST AWARD OF THE PENROSE MEDAL. PMID- 17732150 TI - ON THE DECOMPOSITION OF H2O2. PMID- 17732151 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17732152 TI - EDITORIAL SERVICE. PMID- 17732153 TI - TERMITES IN BUILDINGS. PMID- 17732154 TI - A NATURAL SEISMOGRAPH. PMID- 17732155 TI - THE FRESH-WATER SPONGE, SPONGILLA LACUSTRIS LINN., IN MASSACHUSETTS. PMID- 17732156 TI - THE EFFECT OF POLARIZED LIGHT ON THE GROWTH OF LUMINOUS BACTERIA. PMID- 17732157 TI - MICRO SLIDE RINGS. PMID- 17732158 TI - A METHOD OF DEMONSTRATING ACIDITY OF FOOD VACUOLES IN PARAMECIUM. PMID- 17732159 TI - THE NON-NUCLEATED CELLULAR ELEMENTS OF THE BLOOD. PMID- 17732160 TI - THE OKLAHOMA ACADEMY OF SCIENCE. PMID- 17732161 TI - THE ILLINOIS STATE ACADEMY OF SCIENCE. PMID- 17732162 TI - REPORT OF THE COMMITTEE ON THE PHILOLOGICAL SCIENCES. PMID- 17732163 TI - ON THE PROBLEM OF APPLIED MATHEMATICS. PMID- 17732164 TI - FLORENCE BASCOM 1862-1945. PMID- 17732165 TI - PUBLIC LANDS CONTAINING RADIOACTIVE MINERALS. PMID- 17732166 TI - PLACEMENT OF VETERANS BY THE NATIONAL ROSTER OF SCIENTIFIC AND SPECIALIZED PERSONNEL. PMID- 17732167 TI - THE COORDINATING COMMITTEE OF THE UNITED NATIONS STANDARDS. PMID- 17732168 TI - NEWS FROM ABROAD. PMID- 17732169 TI - ROLE OF UNSATURATED FATTY ACIDS IN CHANGES OF ADIPOSE AND DENTAL TISSUES IN VITAMIN E DEFICIENCY. PMID- 17732170 TI - ARTERIAL ANASTOMOSIS IN DOGS EMPLOYING VEIN GRAFTS FROM CHICKENS AND TURKEYS. PMID- 17732171 TI - THE EFFECT OF PENICILLIN IN EXPERIMENTAL RABBIT SYPHILIS. PMID- 17732172 TI - NON-TOXICITY OF DDT ON CELLS IN CULTURES. PMID- 17732173 TI - IMPROVEMENT IN KEEPING QUALITY OF SUCCULENT PLANTS AND CUT FLOWERS BY TREATMENT UNDER WATER IN PARTIAL VACUUM. PMID- 17732174 TI - THE EFFECT OF THIOURACIL ON TISSUE OXIDASE. PMID- 17732175 TI - MODIFIED METHOD OF EXTRACTING CHOLESTEROL. PMID- 17732176 TI - TEMPERATURES IN SOME DEEP WELLS IN PENNSYLVANIA AND WEST VIRGINIA. PMID- 17732177 TI - RE-EMPLOYMENT OF BIOLOGISTS NOW IN THE ARMY AIR FORCES. PMID- 17732179 TI - THE SUPPRESSION OF CONSUMPTION. PMID- 17732178 TI - THE MEIGEN 1800 NAMES AGAIN. PMID- 17732180 TI - Schmerz-Freude ("Pain-Joy"). PMID- 17732181 TI - HEALTH MATTERS. PMID- 17732182 TI - Action of Caffeine. PMID- 17732184 TI - Anemometry. PMID- 17732183 TI - THE MARINE BIOLOGICAL LABORATORY. PMID- 17732185 TI - Supposed Aboriginal Fish-Weirs in Naaman's Creek, near Claymont, Del. PMID- 17732186 TI - INDUSTRIAL NOTES. PMID- 17732187 TI - Physiology of Flowering: Flowering is hormonally controlled, but the nature of the hormone remains to be elucidated. PMID- 17732188 TI - Recoilless Nuclear Resonance Absorption of Gamma Radiation: A new principle yields gamma lines of extreme narrowness for measurements of unprecedented accuracy. PMID- 17732189 TI - Arms Agency: Executive Order Gives It a Boost at a Time When Its Prestige Is Sagging. PMID- 17732190 TI - Origin of Tektites. PMID- 17732191 TI - Lunar Synodical Period and Widespread Precipitation. AB - Precipitation activity over broad areas appears to be closely associated with the monthly lunisolar cycle. Indexes of precipitation in the continental United States over a continuous 50-year period, and 91-year daily histories of individual stations, reveal that heavy rains occur most frequently in the first and third weeks of the synodical month. PMID- 17732192 TI - Lunar Component in Precipitation Data. PMID- 17732193 TI - Bedrock Geology of the Thiel Mountains, Antarctica. AB - Cordierite-bearing, hyper-sthene-quartz monzonite porphyry, the most widespread rock unit, is intruded by biotite granite and porphyritic biotite granite. Sedimentary and metasedimentary rocks, mainly quartzites and argillites, have been metamorphosed locally to hornfels and have been involved in high-angle faulting. Shear zones are common in the plutonic rocks. PMID- 17732194 TI - Sterility in the Mexican Fruit Fly Caused by Chemicals. AB - Chlorambucil, 4-{p-[bis(2-chloroethyl) amino] phenyl} butyrate, administered in food to the Mexican fruit fly Anastrepha Iudens (Loew) inhibits the growth of testes and reduces egg hatch to almost nothing. Oviposition is not affected. The compound 4-amino-1H-pyrazolo (3.4-d) pyrimidine sulfate inhibits the growth of ovaries and reduces oviposition and fertility. PMID- 17732195 TI - Increase in Diffusible Auxin after Treatment with Gibberellin. AB - When dwarf pea plants, normal pea plants, and sunflower plants were treated with gibberellin, they yielded 3, 2, and 10 times more auxin, respectively, than untreated plants. PMID- 17732196 TI - Salmonella Species in Turtles. AB - Salmonella spp. occur abundantly in the feces of the turtles Testudo graeca and T. hermanni but rarely in other testudines. These organisms do not seem to produce any kind of infection in the turtles. One possible explanation for the infestation is the coprophagic habit of T. graeca and T. hermanni.. PMID- 17732197 TI - Contamination of Vegetation by Tetraethyl Lead. AB - Tetraethyl lead is a normal constituent of vegetation growing along our highways. Washed grass near Denver contained 3000 ppm (in ash) near major intersections and > 50 ppm for 500 feet downwind. Vegetables grown within 25 feet of a road in upstate New York and western Maryland averaged 80 to 115 ppm. PMID- 17732198 TI - Sorbitol Translocation in Apple. AB - A report of glucose translocation, an apparent exception to the hypothesis that sucrose is the major carbohydrate translocated in plants, was investigated. Carbon-14 studies of the carbohydrates in the bark of apple suggest that rather than glucose the sugar alcohol, sorbitol, in addition to sucrose, is a principal compound translocated in this species. PMID- 17732200 TI - Forthcoming Events. PMID- 17732201 TI - SCIENCE NEWS. PMID- 17732199 TI - International Biological Program. PMID- 17732202 TI - THE RELATIONSHIP BETWEEN ELECTRICAL POTENTIALS AND CHEMICAL REACTIVITY. PMID- 17732203 TI - OBITUARY. PMID- 17732204 TI - BODY SIZE AND BODY PROPORTIONS IN RELATION TO GROWTH RATES AND NATURAL SELECTION. PMID- 17732206 TI - THE GROWTH OF STALAGMITES. PMID- 17732205 TI - THE TUBERCLE BACILLUS. PMID- 17732207 TI - THE SWARMING OF AN ANTS. PMID- 17732208 TI - THE SIXTH INTERNATIONAL CONGRESS OF GENETICS. PMID- 17732209 TI - SUCCESSFUL CAGE REARING OF ANOPHELES QUADRIMACULATUS. PMID- 17732210 TI - STIMULATION OF SPAWNING AND CROSSFERTILIZATION BETWEEN AMERICAN AND JAPANESE OYSTERS. PMID- 17732212 TI - THE AUTOGIRO. PMID- 17732211 TI - THE STRUCTURE OF CHROMOSOMES OF ZEA MAYS AS REVEALED BY THE FEULGEN REACTION. PMID- 17732213 TI - RADIO MESSAGES BY PICTURE. PMID- 17732214 TI - THE ETHER DRIFT. PMID- 17732215 TI - THE MEXICAN BEAN BEETLE. PMID- 17732217 TI - THE ELECTRIC SQUIB. PMID- 17732216 TI - THE SPEED OF LIGHT. PMID- 17732219 TI - HODMEN OF SCIENCE. PMID- 17732218 TI - REVERSED SNAILS. PMID- 17732220 TI - SOLAR VARIATION AND THE WEATHER. PMID- 17732222 TI - WALTER DAVID HUNTER. PMID- 17732223 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17732221 TI - THE KANSAS CITY MEETING OF THE AMERICAN ASSOCIATION. PMID- 17732225 TI - THE FLORIDA MAN. PMID- 17732226 TI - A CONSERVATIONIST'S CREED AS TO WILD-LIFE ADMINISTRATION. PMID- 17732224 TI - EVIDENCE ON BASIN RANGE STRUCTURE. PMID- 17732228 TI - A WHALE SHARK (RHINEODON) IN THE GULF OF SIAM. PMID- 17732227 TI - DIPLOID MALES FROM FERTILIZED EGGS IN HYMENOPTERA. PMID- 17732229 TI - HIGH VOLTAGE CATHODE RAYS OUTSIDE THE GENERATING TUBE. PMID- 17732230 TI - THE TRANSFER OF TOBACCO AND TOMATO MOSAIC DISEASE BY THE PSEUDOCOCCUS CITRI. PMID- 17732231 TI - MEETING OF THE EXECUTIVE COMMITTEE OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17732232 TI - This week in science. PMID- 17732233 TI - Funding the SSC. PMID- 17732234 TI - The quality of homoeosis. PMID- 17732235 TI - Sciencescope. PMID- 17732236 TI - Clinton's Technology Policy Emerges. PMID- 17732237 TI - Publication by electronic mail takes physics by storm. PMID- 17732239 TI - A new director for hubble facility. PMID- 17732238 TI - Measures of success at the frontiers. PMID- 17732240 TI - A run is a run is a run. PMID- 17732242 TI - Animal importer admits primate conspiracy. PMID- 17732241 TI - Uncovering a 10-ton hoax. PMID- 17732243 TI - Looking for cancer in nuclear matrix proteins. PMID- 17732244 TI - Analytical titans gather at pittcon to predict the future. PMID- 17732246 TI - Battle lines shift in the great cosmic distance dispute. PMID- 17732245 TI - An analytical triptych. PMID- 17732247 TI - Mediterranean outflow mixing and dynamics. AB - The Mediterranean Sea produces a salty, dense outflow that is strongly modified by entrainment as it first begins to descend the continental slope in the eastern Gulf of Cadiz. The current accelerates to 1.3 meters per second, which raises the internal Froude number above 1, and is intensely turbulent through its full thickness. The outflow loses about half of its density anomaly and roughly doubles its volume transport as it entrains less saline North Atlantic Central water. Within 100 kilometers downstream, the current is turned by the Coriolis force until it flows nearly parallel to topography in a damped geostrophic balance. The mixed Mediterranean outflow continues westward, slowly descending the continental slope until it becomes neutrally buoyant in the thermocline where it becomes an important water mass. PMID- 17732248 TI - Simple systems that exhibit self-directed replication. AB - Biological experience and intuition suggest that self-replication is an inherently complex phenomenon, and early cellular automata models support that conception. More recently, simpler computational models of self-directed replication called sheathed loops have been developed. It is shown here that "unsheathing" these structures and altering certain assumptions about the symmetry of their components leads to a family of nontrivial self-replicating structures, some substantially smaller and simpler than those previously reported. The dependence of replication time and transition function complexity on initial structure size, cell state symmetry, and neighborhood are examined. These results support the view that self-replication is not an inherently complex phenomenon but rather an emergent property arising from local interactions in systems that can be much simpler than is generally believed. PMID- 17732249 TI - The chaotic obliquity of Mars. AB - Numerical integration of the rotation of Mars shows that the obliquity of Mars undergoes large chaotic variations. These variations occur as the system evolves in the chaotic zone associated with a secular spin-orbit resonance. PMID- 17732250 TI - Lidar observations of the meteoric deposition of mesospheric metals. AB - The mesospheric sodium and iron layers at an altitude between about 80 and 110 kilometers are routinely monitored by atmospheric physicists using resonance fluorescence lidar techniques because these constituents are excellent tracers of mesopause chemistry and dynamics. The mesospheric metals are the products of meteoric ablation. Existing ablation profiles are model calculations based in part on radar observations of the ionized background atmosphere left in the wake of high-speed (> 20 kilometers per second) meteoroids. Thin trails of neutral metal atoms, ablated from individual meteoroids, are occasionally observed with high-power lidars. The vertical distribution of 101 sodium and 5 iron meteor trails observed during the past 4 years at Urbana, Illinois; Arecibo, Puerto Rico; and near Hawaii is approximately Gaussian in shape with a centroid height of 89.0 (+/- 0.3) kilometers and a root-mean-square width of 3.3 (+/- 0.2) kilometers. This directly measured ablation profile is nearly the same as the mean iron layer profile but is considerably different from existing models and the distribution of ionized meteor trails observed by radars. A lower limit on the influx to the mesopause region from the lidar meteors is approximately 1.6 x 10(3) sodium and 2.7 x 10(4) iron atoms per second per square centimeter, which corresponds to an annual flux of meteoric debris into the mesosphere of about 2.0 (+/-0.6) gigagrams. Because the lidars can detect only the ablation trails left by the larger meteors, the observations suggest that the actual meteoric influx may be larger than the more recently reported values, which range between 16 and 78 gigagrams per year. PMID- 17732251 TI - Isomers of Small Carbon Cluster Anions: Linear Chains with up to 20 Atoms. AB - The structure of small carbon cluster anions, Cn(-) (4 /=20 and >/= 28 kiloelectron volts, respectively) plasma environment at Jupiter by the low-energy charged particle (LECP) instrument on Voyager 2 have revealed several new and unusual aspects of the Jovian magnetosphere. The magnetosphere is populated from its outer edge into a distance of at least approximately 30 Jupiter radii (R(J)) by a hot (3 x 10(8) to 5 x 10(8) K) multicomponent plasma consisting primarily of hydrogen, oxygen, and sulfur ions. Outside approximately 30 R(J) the hot plasma exhibits ion densities from approximately 10(-1) to approximately 10(-6) per cubic centimeter and energy densities from approximately 10(-8) to 10(-13) erg per cubic centimeter, suggesting a high beta plasma throughout the region. The plasma is flowing in the corotation direction to the edge of the magnetosphere on the dayside, where it is confined by solar wind pressure, and to a distance of approximately 140 to 160 R(J) on the nightside at approximately 0300 local time. Beyond approximately 150 R(J) the hot plasma flow changes into a "magnetospheric wind" blowing away from Jupiter at an angle of approximately 20 degrees west of the sun-Jupiter line, characterized by a temperature of approximately 3 x 10(8) K (26 kiloelectron volts), velocities ranging from approximately 300 to > 1000 kilometers per second, and composition similar to that observed in the inner magnetosphere. The radial profiles of the ratios of oxygen to helium and sulfur to helium ( 1 kilometer per million years) beginning approximately 6 million years ago (Ma). Uplift was a result of the morphology of the Denali fault and a change in motion of the Pacific plate with respect to North America at approximately 5 Ma, which created opposing tangential vectors of relative movement along the fault and forced the intervening crustal blocks upward. PMID- 17734170 TI - Seismic structure of the southern East pacific rise. AB - Seismic data from the ultrafast-spreading (150 to 162 millimeters per year) southern East Pacific Rise show that the rise axis is underlain by a thin (less than 200 meters thick) extrusive volcanic layer (seismic layer 2A) that thickens rapidly off axis. Also beneath the rise axis is a narrow (less than 1 kilometer wide) melt sill that is in some places less than 1000 meters below the sea floor. The small dimensions of this molten body indicate that magma chamber size does not depend strongly on spreading rate as predicted by many ridge-crest thermal models. However, the shallow depth of this body is consistent with an inverse correlation between magma chamber depth and spreading rate. These observations indicate that the paradigm of ridge crest magma chambers as small, sill-like, midcrustal bodies is applicable to a wide range of intermediate- and fast spreading ridges. PMID- 17734171 TI - Stress protection of transgenic tobacco by production of the osmolyte mannitol. AB - The accumulation of sugar alcohols and other low molecular weight metabolites such as proline and glycine-betaine is a widespread response that may protect against environmental stress that occurs in a diverse range of organisms. Transgenic tobacco plants that synthesize and accumulate the sugar alcohol mannitol were engineered by introduction of a bacterial gene that encodes mannitol 1 -phosphate dehydrogenase. Growth of plants from control and mannitol containing lines in the absence and presence of added sodium chloride was analyzed. Plants containing mannitol had an increased ability to tolerate high salinity. PMID- 17734173 TI - Polyethylene bags and solar ultraviolet radiation. PMID- 17734174 TI - Posthumous inspirations. PMID- 17734172 TI - Response. PMID- 17734176 TI - Vignettes: calling for callers. PMID- 17734175 TI - Complexities of feynman. PMID- 17734178 TI - Products & materials. PMID- 17734177 TI - A pandemic reconstrued. PMID- 17734179 TI - ON THE TEACHING OF MATHEMATICS. PMID- 17734180 TI - CULTURAL INTERCHANGE BETWEEN THE SOVIET UNION AND THE UNITED STATES. PMID- 17734182 TI - ALBERT KINGSBURY. PMID- 17734181 TI - FRERE MARIE-VICTORIN. PMID- 17734183 TI - THE AMERICAN ACADEMY OF TROPICAL MEDICINE. PMID- 17734184 TI - AWARD OF THE WALTER REED MEDAL. PMID- 17734185 TI - MEDALS AWARDED BY THE ROYAL SOCIETY. PMID- 17734186 TI - THE NATIONAL ACADEMY OF SCIENCES. PMID- 17734187 TI - AWARD OF THE PERKIN MEDAL. PMID- 17734189 TI - IMPROBABILITY AND IMPOSSIBILITY. PMID- 17734190 TI - IMPROBABILITY AND IMPOSSIBILITY. PMID- 17734188 TI - UTILIZATION OF "PORE SPACES" OF SEMIPERMEABLE MEMBRANES. PMID- 17734191 TI - SMITH COLLEGE CONFERENCE ON PLANT EMBRYO CULTURE. PMID- 17734192 TI - THE CHOLINESTERASES IN THE LIGHT OF RECENT FINDINGS. PMID- 17734193 TI - THE ANTIBACTERIAL ACTION OF PENICILLIN AGAINST GRAM NEGATIVE ORGANISMS. AB - It is apparent that penicillin exerts an antibacterial action against Gram negative as well as Gram positive organisms. This property of penicillin becomes more apparent in high potency preparations. It is possible that a form of penicillin showing greater activity against Gram negative organisms may exist. Studies on the nature of such a substance and on the in vivo action of penicillin against Gram negative organisms are in progress. PMID- 17734194 TI - RELATION OF DOSAGE TO SURVIVAL TIME OF ARSENITE-INJECTED ROACHES. PMID- 17734196 TI - A CONSTANT VACUUM APPARATUS. PMID- 17734195 TI - THE MOTION OF SMALL PARTICLES IN MAGNETIC FIELDS. PMID- 17734197 TI - THE BLOOD-SALINE COAGULATION TIME TEST. PMID- 17734199 TI - THE DEPARTMENT OF AGRICULTURE AND THE FOOD SITUATION. PMID- 17734198 TI - THE PRODUCTION OF SCIENTIFIC KNOWLEDGE. PMID- 17734200 TI - THE PITTSBURGH MEETING OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17734202 TI - A NOTE ON THE "AGE AND AREA" HYPOTHESIS. PMID- 17734201 TI - THE MANUFACTURE OF OPTICAL GLASS IN AMERICA. PMID- 17734204 TI - BOSTON MEETING OF THE AMERICAN CHEMICAL SOCIETY. PMID- 17734203 TI - THE UFFINGTON SHALE OF WEST VIRGINIA AND ITS SUPPOSED MARINE FAUNA. PMID- 17734205 TI - From Alamogordo to West Milton. PMID- 17734207 TI - News of Science. PMID- 17734206 TI - Men and Their Sciences. PMID- 17734210 TI - Scientific Meetings. PMID- 17734208 TI - Miscellaneous Publications. PMID- 17734211 TI - Squaring the record. PMID- 17734212 TI - Phenylalanyl tRNA Available. PMID- 17734214 TI - Interdisciplinary communication. PMID- 17734213 TI - Oil pollution: unsolved problems. PMID- 17734215 TI - The tortoise and the jet. PMID- 17734216 TI - Mathematical Theory of Automobile Traffic: Improved understanding and control of traffic flow has become a fast-growing area of scientific research. PMID- 17734218 TI - Nuclear spread: quest for a treaty is receiving new attention. PMID- 17734219 TI - Overhauling the draft system: hard times for the reformers. PMID- 17734220 TI - Pollack to head state science office. PMID- 17734221 TI - New criteria to hurricane study. PMID- 17734222 TI - 200 bev: close senate vote defeats effort to delay weston project. PMID- 17734223 TI - A "scientific luxury". AB - In the lay press, the New York Times has long been a leading advocate and defender of federal support for basic research. On 16 July, however, the Times departed from this pattern to question the advisability of proceeding at this time with the construction of the Weston accelerator. Leading off with an editorial on last week's riots in Newark, New Jersey, titled, "The Gravest Responsibility . . .," the Times followed with an editorial on the 200-Bev accelerator, titled ". . . Vs. Scientific Luxury." PMID- 17734224 TI - Radio method for the precise measurement of the rotation period of the Earth. AB - Radio interferometry with independent high-precision clocks, without a high frequency communication channel between the stations, is now a possibility. It allows the stations to be as far apart as the earth can accommodate. This then makes the radio band from 10- to 60-centimeters wavelength the best frequency range for high-precision angular measurements, since the variability of the atmosphere is less disturbing there than in the optical band. PMID- 17734225 TI - Implications for Geophysics of the Precise Measurement of the Earth's Rotation. AB - A radio interferometer could yield an error on the order of 10(-9) second at the semidiurnal frequency. With errors of this magnitude, yearly changes in the rate at which the earth's rotation is slowing down could be determined. The proposed interferometer could also yield significant improvements in the determination of the Love number k and its variation with frequency, and in the changes in angular momentum of the atmosphere for periods greater than 1 week. PMID- 17734226 TI - Zeolitization of tuffaceous rocks of the green river formation, wyoming. AB - The alkali-rich zeolites mordenite and clinoptilolite have been discovered in tuffaceous rocks of the Green River Formation, Wyoming. This occurrence strongly supports the alteration of glass to alkali-rich zeolite to analcime as the paragenetic sequence of alteration of tuffaceous rocks deposited in ancient Lake Gosiute. PMID- 17734227 TI - High-Conductivity Solid Electrolytes: MAg4I5. AB - The solid electrolytes MAg(4)I(5), where M may be potassium, rubidium, or ammonium, have an ionic conductivity of 0.2 (ohm cm)(-1) at 20 degrees C. Although pure CsAg(4)I(5) does not form, partial substitution of cesium into the M position was obtained. The high-conducting phases of KAg(4)I(5) and RbAg(4)I(5) may be quenched to low temperatures, where they transform to resistive phases at 136 degrees and -155 degrees C, respectively. PMID- 17734228 TI - Crystal Structure of the Solid Electrolyte, RbAg4I5. AB - The crystal structure of the solid electrolyte RbAg(4)I(5) has been determined from single-crystal x-ray diffraction counter data. There are four RbAg(4)I(5) in a cubic unit cell with a = 11.24 A. The structure refinement, by least squares, is based on space group P4(1)3 (O(7)). The arrangement of the iodide ions is similar to that of the manganese atoms in beta-manganese, and provides 56 iodide tetrahedra per unit cell, which share faces in such manner as to provide diffusion paths for the silver ions. The occurrence of the two low-temperature phases of RbAg(4)I(5) has been established by x-ray diffraction and optical examination. PMID- 17734229 TI - Toxicity of antibiotics in laboratory rodents. PMID- 17734231 TI - ADDRESS OF THE PRESIDENT TO THE PHYSIOLOGICAL SECTION OF THE BRITISH ASSOCIATION. PMID- 17734230 TI - Stromatolites. PMID- 17734232 TI - CHEMISTRY AT THE BRITISH ASSOCIATION. PMID- 17734235 TI - THE GRANT SARCOPHAGUS. PMID- 17734233 TI - GEOGRAPHY AT THE BRITISH ASSOCIATION. PMID- 17734234 TI - IS THE DENVER FORMATION LACUSTRINE OR FLUVIATILE? PMID- 17734236 TI - BOTANICAL NOTES. PMID- 17734237 TI - NOTES ON INORGANIC CHEMISTRY. PMID- 17734239 TI - THE LABORATORIES OF THE BRITISH GOVERNMENT. PMID- 17734238 TI - THE DEDICATION OF THE YERKES ASTRONOMICAL OBSERVATORY. PMID- 17734240 TI - AMERICAN MATHEMATICAL SOCIETY. PMID- 17734241 TI - SOURCE OF THE FAMOUS THETFORD LIMBURGITE. PMID- 17734242 TI - THE BOSTON PLANS FOR A NEW YORK BOTANICAL GARDEN. PMID- 17734243 TI - RESIGNATION OF THE DIRECTOR OF LICK OBSERVATORY. PMID- 17734245 TI - LANTERN TRANSPARENCIES. PMID- 17734244 TI - DANGERS OF FORMALIN. PMID- 17734247 TI - SCIENCE NEWS. PMID- 17734246 TI - MORE DICTIONARY ZOOLOGY. PMID- 17734248 TI - PLANNING THE LAND FOR THE FUTURE. PMID- 17734249 TI - ELEMENT 91. PMID- 17734250 TI - OBITUARY. PMID- 17734251 TI - THE MOTION OF GLACIERS. PMID- 17734253 TI - A TROPICAL FISH CROSS. PMID- 17734254 TI - SUMMER MEETING OF THE AMERICAN MATHEMATICAL SOCIETY. PMID- 17734252 TI - THE DISTRIBUTION OF FUNDS FOR RESEARCH. PMID- 17734255 TI - NEW DISTRIBUTIONAL RECORD FOR THE MEDUSA CRASPEDACUSTA. PMID- 17734256 TI - DENTAL CONFERENCE AT YALE UNIVERSITY. PMID- 17734257 TI - ATTACHING REFRACTORY PARAFFINE SECTIONS TO THE GLASS SLIP. PMID- 17734258 TI - LITHOTYPING IN MINIATURE AS A MEANS OF SCIENTIFIC PUBLICATION. PMID- 17734259 TI - LAKE VEGETATION AS A POSSIBLE SOURCE OF FORAGE. PMID- 17734260 TI - THE STRUCTURE OF THE CARDIAC AGLUCONES. PMID- 17734261 TI - Prizes and Awards. PMID- 17734262 TI - Meetings & Conferences. PMID- 17734263 TI - Radioactive Fallout in the United States. PMID- 17734265 TI - Miscellaneous Publications. PMID- 17734264 TI - Warder Clyde Allee: Ecologist and Ethologist. PMID- 17734266 TI - More on Induction of Tooth Defects by Thermal Shock. PMID- 17734268 TI - Isomerization of beta-Carotene with Sunlight. PMID- 17734267 TI - Note on the Al and Si Positions in Ordered Na and K Feldspars. PMID- 17734269 TI - THE AMERICAN GEOPHYSICAL UNION. PMID- 17734270 TI - ACETYLCHOLINE AND THE PHYSIOLOGY OF THE NERVOUS SYSTEM. PMID- 17734272 TI - RULES FOR AFFILIATED HOSPITAL UNITS OF THE OFFICE OF CIVILIAN DEFENSE. PMID- 17734271 TI - MONT ROGERS REID. PMID- 17734273 TI - SEARCH FOR MINERALS IN THE MICHIGA UPPER PENINSULA. PMID- 17734274 TI - THE OPTICAL SOCIETY OF AMERICA. PMID- 17734275 TI - BOTANICAL SURVEY OF THE ALCAN HIGHWAY. PMID- 17734276 TI - EXPEDITION EXHIBITION OF THE NEW YORK ZOOLOGICAL SOCIETY. PMID- 17734277 TI - RARE CHEMICALS. PMID- 17734279 TI - BIOLOGY AND THE KILGORE BILL. PMID- 17734278 TI - THE MOBILIZATION OF SCIENCE. PMID- 17734280 TI - THE MOSCOW SCHOOL OF TOPOLOGY. PMID- 17734281 TI - THE ILLINOIS STATE ACADEMY OF SCIENCE. PMID- 17734282 TI - ISOLATION AND PROPERTIES OF CHICKEN ERYTHROCYTE NUCLEI. AB - (1) A method has been described for the isolation of chicken erythrocyte nuclei using saponin to lake the cells. Nuclei prepared by this method have been compared with nuclei prepared by the method of Laskowskie and with nuclei prepared by a citric acid method, particularly in regard to respiration. (2) The total lipid content of the nuclei is about 14 per cent. and the desoxyribonucleic acid content is about 45 per cent. (3) A yellow pigment contained in the nuclei appears to be xanthophyll. (4) A gel formed by the nuclei at pH 8.5 in the presence of ammonia and the absence of other cations is described. PMID- 17734283 TI - FRACTIONAL CEPHALIN-CHOLESTEROL FLOCCULATION IN HEPATIC DISEASE. PMID- 17734284 TI - STUDIES ON PERIPHERAL VISUAL ACUITY. PMID- 17734285 TI - A MACROCHEMICAL REACTION FOR THE DETECTION OF PEACH MOSAIC. PMID- 17734287 TI - THE NATURE OF HEAT. PMID- 17734286 TI - A METHOD FOR NARCOTIZING HOLOTHURIANS. PMID- 17734289 TI - EARLY MAN IN SOUTH AMERICA. PMID- 17734288 TI - THE PBOBLEM OF MECHANICAL FLIGHT. PMID- 17734290 TI - THE NEW ALLEGHENY OBSERVATORY. PMID- 17734291 TI - A REMEDY WORSE THAN THE DISEASE. PMID- 17734292 TI - SYMPTOMATIC DEVELOPMENT OF CANCER. PMID- 17734294 TI - Letter to the editor. PMID- 17734293 TI - REVERSIBLE CHANGES IN PERMEABILITY PRODUCED BY ELECTROLYTES. PMID- 17734295 TI - Does science neglect society? PMID- 17734296 TI - Letter to the editor. PMID- 17734297 TI - Decline of the lobster. PMID- 17734298 TI - Openings for negro engineers. PMID- 17734300 TI - A point of view. PMID- 17734299 TI - Student anxiety. PMID- 17734301 TI - Education reform: britain tries it top to bottom. PMID- 17734303 TI - Aldabra: reprieve for an island. PMID- 17734304 TI - Chondritic meteorites and the lunar surface. AB - The landing dynamics of and soil penetration by Surveyor I indicated that the lunar soil has a porosity in the range 0.35 to 0.45. Experiments with Surveyor III's surface sampler for soil mechanics show that the lunar soil is approximately incompressible (as the word is used in soil mechanics) and that it has an angle of internal friction of 35 to 37 degrees; these results likewise point to a porosity of 0.35 to 0.45 for the lunar soil. Combination of these porosity measurements with the already-determined radar reflectivity fixes limits to the dielectric constant of the grains of the lunar soil. The highest possible value is about 5.9, relative to vacuum; a more plausible value is near 4.3. Either figure is inconsistent with the idea that the lunar surface is covered by chondritic meteorites or other ultrabasic rocks. The data point to acid rocks, or possibly vesicular basalts; carbonaceous chondrites are not excluded. PMID- 17734305 TI - Galaxies as gravitational lenses. AB - The probability that a galaxy gathers light from another remote galaxy, and deflects and focuses it toward an observer on Earth, is calculated according to various cosmologic models. I pose the question of whether an object called a quasar is a single, intrinsically luminous entity or the result of accidental alignment, along the line of sight, of two normal galaxies, the more distant of which has its light amplified by the gravitational-lens effect of the nearer galaxy. If galaxies are distributed at random in the universe, the former alternative is true. But, if we assume that most galaxies exist in pairs, we can find about 30 galaxies occurring exactly one behind the other in such a way as to enable amplification of the order of 50. This model explains also the variations in intensity in quasars, but fails to explain others of their observed properties. PMID- 17734306 TI - Landslide noise. AB - Acoustical monitoring of real landslides has revealed the existence of subaudible noise activity prior to failure and has enabled prediction of the depth of the seat of sliding when conducted in boreholes beneath the surface. Recordings of noise generated in small slopes of moist sand, tilted to failure in laboratory tests, have been analyzed to determine the foci of discrete subaudible noise events. The noises emitted shortly before failure were plotted close to the true sliding surface observed after failure. The foci of earlier events lay either within the central portion of the sliding mass or in a region behind the failure surface. The head and toe zones were devoid of strong seismic activity. PMID- 17734307 TI - Splashing of drops on shallow liquids. AB - The events that follow the splashing of a drop on a liquid depend on the depth of the liquid. When the depth is less than about 5 millimeters the crown that is ejected is more unstable than that from a splash on a deep liquid. As the depth is decreased from 25 to 7 millimeters, there is an increase in the maximum height to which the Rayleigh jet rises, and in the number of drops that break away from the jet. With depths less than 7 millimeters these two quantities fall off sharply, and no jet drops are produced for depths less than about 3 millimeters. PMID- 17734308 TI - AAAS General and Sectional Symposia. PMID- 17734309 TI - Catalysis by transition metals: metal-carbon double and triple bonds. AB - Several well-characterized transition metal catalysts contain a metal-carbon double bond or a metal-carbon triple bond. In other homogeneous (or heterogeneous) catalyst systems in which the metal is likely to be in a relatively high oxidation state, such as molybdenum(VI) or tungsten(VI), metal carbon multiple bonds may play an important role. Some recent results suggest that even supposedly well understood reactions such as ethylene polymerization may actually involve catalysts that behave as if they contained a metal-carbon double bond instead of a metal-carbon single bond. The chemistry of metal-carbon double and triple bonds should eventually complement and perhaps. overlap the known chemistry of complexes containing metal-oxygen double bonds or metal nitrogen triple bonds, respectively; unique catalytic reactions involving carbon, nitrogen, and oxygen ligands multiply bonded to transition metals are therefore possible. PMID- 17734310 TI - Rare and endangered species of plants--the soviet side. AB - In late 1972, the Soviet Union embarked on a program to identify and document plant species that are threatened with extinction. Perhaps 2000 species in the Soviet Union are in need of monitoring or protective measures, while nearly 200 may be in immediate danger of extinction. Currently, the Soviet Union has an official, national list of endangered species, and each of the 15 republics has prepared a regional list. Once a revised national list is prepared, Soviet scientists hope that the Supreme Soviet will pass a law protecting those species. A corresponding law for endangered animals was passed in 1980. PMID- 17734311 TI - New sources for fuel and materials. AB - A selection of new plant sources with high potential for production of chemicals and liquid fuels is reviewed. Some productivity data are given, and suggestions are made for modification of both the product character and the productivity of the plants. PMID- 17734312 TI - The University's Entry Fee to Federal Research Programs. AB - The university pays for its benefits from a federally financed project with its own investments in the faculty scientist and not, as is often assumed, by its absorption of project costs that are not reimbursed by the government. An analysis of the exchange of resources between the university, the scientist, the discipline, and the government shows, however, that by absorbing costs the institution gains acceptance as a host for federal research. Funds for this ticket of admission are drawn away from several groups on the campus. In exploring whether there should be such an entry fee, the pragmatic response of the National Commission on Research is considered. PMID- 17734313 TI - The radwaste paradox. PMID- 17734315 TI - Fallout from nuclear power in space. PMID- 17734314 TI - Waste bill approved. PMID- 17734316 TI - Stanford patent claim is put under wraps. PMID- 17734317 TI - After the Shake-up at NSF. PMID- 17734318 TI - Lame ducks spurn arthritis institute, energy R & d. PMID- 17734319 TI - Einstein Papers Project Gets NSF Interim Grant. PMID- 17734320 TI - Loophole closed in quantum mechanics test. PMID- 17734321 TI - Fossil lucy grows younger, again. PMID- 17734322 TI - Annual meeting detroit. PMID- 17734324 TI - Urban environmental efforts. PMID- 17734323 TI - Conditions of soviet technology. PMID- 17734325 TI - Prices of books. PMID- 17734327 TI - Ores. PMID- 17734326 TI - Synapsids and evolution. PMID- 17734328 TI - Very-Long-Baseline Radio Interferometry: The Mark III System for Geodesy, Astrometry, and Aperture Synthesis. AB - The Mark III very-long-baseline interferometry (VLBI) system allows recording and later processing of up to 112 megabits per second from each radio telescope of an interferometer array. For astrometric and geodetic measurements, signals from two radio-frequency bands (2.2 to 2.3 and 8.2 to 8.6 gigahertz) are sampled and recorded simultaneously at all antenna sites. From these dual-band recordings the relative group delays of signals arriving at each pair of sites can be corrected for the contributions due to the ionosphere. For many radio sources for which the signals are sufficiently intense, these group delays can be determined with uncertainties under 50 picoseconds. Relative positions of widely separated antennas and celestial coordinates of radio sources have been determined from such measurements with 1 standard deviation uncertainties of about 5 centimeters and 3 milliseconds of arc, respectively. Sample results are given for the lengths of baselines between three antennas in the United States and three in Europe as well as for the arc lengths between the positions of six extragalactic radio sources. There is no significant evidence of change in any of these quantities. For mapping the brightness distribution of such compact radio sources, signals of a given polarization, or of pairs of orthogonal polarizations, can be recorded in up to 28 contiguous bands each nearly 2 megahertz wide. The ability to record large bandwidths and to link together many large radio telescopes allows detection and study of compact sources with flux densities under 1 millijansky. PMID- 17734330 TI - Bleaching of rhabdoms in eyes of intact butterflies. AB - The photochemistry of butterfly rhabdoms has properties that had been associated exclusively with the photoreceptor organelles of vertebrates. Noninvasive measurements of the absorbance spectra of rhabdoms in intact butterflies show that their rhodopsins are converted by light to metarhodopsins that decay from the rhabdom in the dark. A total bleach is possible because the first-order decay of metarhodopsin is considerably faster than the kinetically more complicated recovery of rhodopsin. PMID- 17734329 TI - Detection of a Compact Radio Source near the Center of a Gravitational Lens: Quasar Image or Galactic Core? AB - By use of a new, very sensitive interferometric system, a faint, compact radio source has been detected near the center of the galaxy that acts as the main part of a gravitational lens. This lens forms two previously discovered images of the quasar Q09S7+561, which lies in the direction of the constellation Ursa Major. The newly detected source has a core smaller than 0.002 arc second in diameter with a flux density of 0.6 +/- 0.1 millijansky at the 13-centimeter wavelength of the radio observations. This source could be the predicted third image of the transparent gravitational lens, the central core of the galaxy, or some combination of the two. It is not yet possible to choose reliably between these alternatives. PMID- 17734331 TI - Meetings & Conferences. PMID- 17734333 TI - Introducing a New Editor of the A.A.A.S. Journals. PMID- 17734332 TI - High-Frequency Scatter Sounding Experiments at the National Bureau of Standards. PMID- 17734334 TI - Scientific Property. PMID- 17734335 TI - Preparation of High-Purity Lithium Metal by Vacuum Distillation. PMID- 17734336 TI - Fashions in Medicine and Science. PMID- 17734337 TI - Autism, stress, and ethology. PMID- 17734339 TI - Letters to the editor. PMID- 17734338 TI - Oil resource estimates. PMID- 17734340 TI - Letters to the editor. PMID- 17734342 TI - Letters to the editor. PMID- 17734341 TI - Letters to the editor. PMID- 17734343 TI - Methysergide dosage. PMID- 17734344 TI - University reform. PMID- 17734345 TI - Career education and liberal arts. PMID- 17734346 TI - NSF: Congress Takes Hard Look at Behavioral Science Course. PMID- 17734347 TI - Fundamental setback for fundamentalists. PMID- 17734348 TI - NIH, HEW Nominees. PMID- 17734349 TI - Citation analysis: a new tool for science administrators. PMID- 17734350 TI - Stanford campus debates fate of student program. PMID- 17734351 TI - Gov. Hathaway: Interior Nominee's "Quality Growth%" Is Going Sour. PMID- 17734352 TI - Crop forecasting from space: toward a global food watch. PMID- 17734353 TI - Diabetes (II): Model Systems Indicate Viruses a Cause. PMID- 17734354 TI - The pancreas. PMID- 17734355 TI - Office of opportunities in science: the professional associations and equal opportunity. PMID- 17734356 TI - Pioneer 10 and pioneer 11. PMID- 17734357 TI - Scientific results from the pioneer 11 mission to jupiter. PMID- 17734358 TI - Pioneer 11 encounter: preliminary results from the ames research center plasma analyzer experiment. AB - Pioneer 11 observations of the interaction of Jupiter's magnetosphere with the distant solar wind have confirmed the earlier Pioneer 10 observations of the great size and extreme variability of the outer magnetosphere. The nature of the plasma transitions across Jupiter's bow shock and magnetopause as observed on Pioneer 10 have also been confirmed on Pioneer 11. However, the northward direction of the Pioneer 11 outbound trajectory and the distance of the final magnetopause crossing (80 Jupiter radii) now suggest that Jupiter's magnetosphere is extremely broad with a half-thickness (normal to the ecliptic plane in the noon meridian) which is comparable to or greater than the sunward distance to the nose. PMID- 17734359 TI - Jupiter's Magnetic Field. Magnetosphere, and Interaction with the Solar Wind: Pioneer 11. AB - The Pioneer 11 vector helium magnetometer provided precise, contititious measurements of the magnetic fields in interplanetary space, inside Jupiter's magnetosphere, and in the near vicinity of Jupiter. As with the Pioneer 10 data, evidence was seen of the dynanmic interaction of Jupiter with the solar wind which leads to a variety of phenomena (bow shock, upstream waves, nonlinear magnetosheath impulses) and to changes in the dimension of the dayside magnetosphere by as much as a factor of 2. The magnetosphere clearly appears to be blunt, not disk-shaped, with a well-defined outer boundary. In the outer magnetosphere, the magnetic field is irregular but exhibits a persistent southward component indicative of a closed magnetosphere. The data contain the first clear evidence in the dayside magnetosphere of the current sheet, apparently associated with centrifugal forces, that was a donminatnt feature of the outbound Pionieer 10 data. A modest westward spiraling of the field was again evident inbound but not outbound at higher latitudes and nearer the Sun-Jupiter direction. Measurements near periapsis, which were nearer the planet and provide better latitude and longitude coverage than Pioneer 10, have revealed a 5 percent discrepancy with the Pioneer 10 offset dipole mnodel (D(2)). A revised offset dipole (6-parameter fit) is presented as well as the results of a spherical harmonic analysis (23 parameters) consisting of an interior dipole, quadrupole, and octopole and an external dipole and quadrupole. The dipole moment and the composite field appear moderately larger than inferred from Pioneer 10. Maximum surface fields of 14 and 11 gauss in the northern and southern hemispheres are inferred. Jupiter's planetary field is found to be slightly more irregular than that of Earth. PMID- 17734360 TI - Jupiter revisited: first results from the university of chicago charged particle experiment on pioneer 11. AB - During the December 1974 Pioneer 11 Jupiter encounter our experiment provided measurements of Jovian energetic protons and electrons both in the magnetic equatorial zone and at previously unexplored high magnetic latitudes. Many of the observations and conclusions from the Pioneer 10 encounter in 1973 were confirmed, with several important exceptions and new findings. We report evidence from Pioneer 11 for protons ( approximately 1 million electron volts) of Jovian origin in interplanetary space. In the outer magnetosphere particle intensities at high magnetic latitudes were comparable to those observed in the equatorial zone, and 10-hour variations in particle intensities and spectra were observed at both high and low magnetic latitudes. Therefore, confinement of particles in the outer magnetosphere to a thin equatorial magnetodisc is adequate neither as a description of the particle distribution nor as a complete explanation of the 10 hour variations. Pioneer 11 data support a model in which the intensity varies with a 10-hour period in phase throughout the sunward side of the magnetosphere and is relatively independent of position within the magnetosphere. Transient, highly anisotropic bursts of protons with energies of approximately 1 million electron volts observed near the orbit of Ganymede suggest local acceleration in some regions of the magnetosphere. In the inner core where particles are stably trapped, a maximum in the high-energy nucleonic flux was again found, corresponding to the Pioneer 10 maximum at approximately 3.4 Jupiter radii (R(J)), which is apparently a persistent feature of, the inner radiation zone. In addition, Pioneer 11 data indicate two more local maxima in the nucleonic flux inside 3.4 R(J), one of which may be associated with absorption by Amalthea, and a maximum intensity at 1.9 R(J) more than 20 times that at 3.4 R(J), The flux of relativistic electrons reached a maximum on the magnetic equator at 1.8 R(J), only slightly less its closest approach at 3.1 R(J). PMID- 17734362 TI - Jovian protons and electrons: pioneer 11. PMID- 17734361 TI - Pioneer 11 observations of energetic particles in the jovian magnetosphere. AB - Knowledge of the positional distributions, absolute intensities, energy spectra, and angular distributions of energetic electrons and protons in the Jovian magnetosphere has been considerably advanced by the planetary flyby of Pioneer 11 in November-December 1974 along a quite different trajectory from that of Pioneer 10 a year earlier. (i) The previously reported magnetodisc is shown to be blunted and much more extended in latitude on the sunward side than on the dawn side. (ii) Rigid corotation of the population of protons E(p) approximately 1 million electron volts in the magnetodisc is confirmed. (iii) Angular distributions of energetic electrons E(e) > 21 million electron volts in the inner magnetosphere are shown to be compatible with the Kennel-Petschek whistler-mode instability. (iv) A diverse body of magnetospheric effects by the Jovian satellites is found. (v) Observations of energetic electrons in to a radial distance of 1.59 Jovian radii provide a fresh basis for the interpretation of decimetric radio noise emission. PMID- 17734363 TI - Radiation belts of jupiter: a second look. AB - The outbound leg of the Pioneer 11 Jupiter flyby explored a region farther from the equator than that traversed by Pioneer 10, and the new data require modification or augmentation of the magnetodisk model based on the Pioneer 10 flyby. The inner moons of Jupiter are sinks of energetic particles and sometimes sources. A large spike of particles was found near lo. Multiple peaks occurred in the particle fluxes near closest approach to the planet; this structure may be accounted for by a complex magnetic field configuration. The decrease in proton flux observed near minimum altitude on the Pioneer 10 flyby appears attributable to particle absorption by Amalthea. PMID- 17734364 TI - The imaging photopolarimeter experiment on pioneer 11. AB - For 2 weeks continuous imaging, photometry, and polarimetry observations were made of Jupiter and the Galilean satellites in red and blue light from Pioneer 11. Measurements of Jupiter's north and south polar regions were possible because the spacecraft trajectory was highly inclined to the planet's equatorial plane. One of the highest resolution images obtained is presented here along with a comparison of a sample of our photometric and polarimetric data with a simple model. The data seem consistent with increased molecular scattering at high latitudes. PMID- 17734365 TI - Pioneer 11 infrared radiometer experiment: the global heat balance of jupiter. AB - Data obtained by the infrared radiometers on the Pioneer 10 and Pioneer 11 spacecraft, over a large range of emission angles, have indicated an effective temperature for Jupiter of 125 degrees +/- 3 degrees K. The implied ratio of planetary thermal emission to solar energy absorbed is 1.9+/-0.2, a value not significantly different from the earth-based estimate of 2.5+/-0.5. PMID- 17734366 TI - Pioneer 11 meteoroid detection experiment: preliminary results. AB - The concentration of meteoroids of mass ~ 10(-8) gram in interplanetary space, in the asteroid belt, and near Jupiter has been measured. The data confirm the Pioneer 10 observation that the asteroid belt is not highly populated with small meteoroids, suggest that the high concentration of small particles around Jupiter is the result of gravitational focusing, and provide an indication of the mass distribution of meteoroids in interplanetary space. PMID- 17734368 TI - Gravity field of jupiter from pioneer 11 tracking data. AB - Significantly improved values of the zonal gravity harmonic coefficients J(39) J(4), and J(6) of Jupiter have been obtained from a preliminary analysis of Pioneer 11 spacecraft Doppler data taken while the spacecraft was near Jupiter. The new results, which will have an important application as boundary conditions for theoretical models of Jupiter's interior. are consistent with a planet in hydrostatic equilibrium. PMID- 17734367 TI - Atmosphere of jupiter from the pioneer 11 s-band occultation experiment: preliminary results. AB - Two additional radio occultation measurements of the atmosphere of Jupiter were obtained with Pioneer 11. The entry measurement leads to a temperature profile that is substantially in agreement with those obtained with Pioneer 10, showing temperatures much higher than those derived from other observations. The exit measurement is not usable because of the discontinuous drift of the spacecraft auxiliary oscillator, presumably due to the trapped radiation belts of Jupiter. The combination of two Pioneer 10 measurements and one Pioneer 11 measurement yields an oblateness of 0.06496 at 1 millibar and 0.06547 at 160 millibars. Measurements in the Jovian ionosphere indicate a number of layers distributed over about 3000 kilometers, with a topside temperature of about 750 K. PMID- 17734369 TI - Stratospheric dust-aerosol event of november 1974. AB - A strong incursion of dust and aerosol at an altitude of 20 kilometers was noted over Baja California and southern Arizona in mid-November 1974, as indicated by bluish-ashen daylight skies and colorful twilight glows of the type usually associated with volcanic eruptions. Infrared satellite observations and reports from other sources eliminated a possible oceanic origin in the eastern Pacific. The stratum is probably from the extensive eruption of Volcan de Fuego in Gautemala in October 1974. PMID- 17734370 TI - Self-control of occipital theta activity and task performance. PMID- 17734371 TI - PARASITISM AS A FACTOR IN DISEASE. PMID- 17734372 TI - THE FIRST APPEARANCE OF THE TRUE MASTODON IN AMERICA. PMID- 17734373 TI - BIOLOGICAL CONTROL OF DESTRUCTIVE INSECTS. PMID- 17734374 TI - A DEFENSE OF PROFESSOR NEWCOMB'S LOGIC. PMID- 17734375 TI - A LONGLIVED WOODBORER. PMID- 17734376 TI - A BACTERIAL DISEASE OF GLADIOLUS. PMID- 17734378 TI - THE COAST AND GEODETIC SURVEY EXHIBIT AT CINCINNATI. PMID- 17734377 TI - THE AMERICAN CHEMICAL SOCIETY. PMID- 17734379 TI - ENGLISH RAILROAD SPEEDS. PMID- 17734381 TI - Preparation of Japanese 'Koji.'. PMID- 17734380 TI - SCIENTIFIC NEWS IN WASHINGTON. PMID- 17734382 TI - The Proposed National Zoological Park. PMID- 17734383 TI - ELECTRICAL SCIENCE. PMID- 17734384 TI - A Standard Thermometric Scale. PMID- 17734385 TI - The Use of the Microscope as a Practical Test for Oleomargarine. PMID- 17734387 TI - REPORT ON PROGRESS IN NON-EUCLIDEAN GEOMETRY. PMID- 17734386 TI - Turner's Explorations in Alaska. PMID- 17734389 TI - SULLIVANT DAY. PMID- 17734388 TI - BOTANY AT THE COLUMBUS MEETING OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17734390 TI - SECTION D (ZOOLOGY) AT THE DOVER MEETING OF THE BRITISH ASSOCIATION. PMID- 17734391 TI - THE DIoeligCISM OF THE FIG IN ITS BEARING UPON CAPRIFICATION. PMID- 17734392 TI - DISCUSSION AND CORRESPONDENCE. PMID- 17734393 TI - THE THIRD PRINCETON EXPEDITION TO PATAGONIA. PMID- 17734394 TI - A LONG PHOTOGRAPHIC TELESCOPE. PMID- 17734395 TI - Assistting Less Developed Countries. PMID- 17734397 TI - Research Overhead. PMID- 17734396 TI - The East Pacific Rise. PMID- 17734398 TI - "Science" and Advertising: the Federal Trade Commission Is Seeking a Way to Curb Abuses. PMID- 17734399 TI - State Department Restrictions on Meeting Participation Questioned. PMID- 17734400 TI - Some Effects of Ionizing Radiation on Translocation in Plants. AB - Petioles and apical regions of Phaseolus vulgaris var. Black Valentine were subjected to ionizing radiation to study the effect on the translocation process. Petiole irradiation produced no discernible effect. Inhibition of translocation to the irradiated meristems was reversed by application of the auxin naphthaleneacetic acid. PMID- 17734401 TI - Use of Pectinase in Preparation of Mitochondria from Tobacco-Tissue Cultures. AB - Mitochondrial particles were isolated from tobacco cells in tissue cultures which were disintegrated with pectinase. The pectinase treatment of the tissue cultures reduced the dry weight of the particulate preparations and eliminated glutinous material, but caused little change in oxidative and phosphorylative activities. The pectinase apparently did not affect the enzymatically active sites of the particles. PMID- 17734402 TI - Left-handed Subjects. PMID- 17734403 TI - Letters to the Editor. PMID- 17734404 TI - Forthcoming Events. PMID- 17734405 TI - Migration of Marine Organisms. PMID- 17734406 TI - "THE PHYSICIAN OF TO-MORROW". PMID- 17734407 TI - DEDICATION OF THE NEW MUSEUM BUILDING OF THE CALIFORNIA ACADEMY OF SCIENCES. PMID- 17734408 TI - THE CENSUS OF FUR SEALS, 1914 AND 1915. PMID- 17734409 TI - IS DYNAMICS A PHYSICAL SCIENCE? PMID- 17734411 TI - FLASHING OF FIREFLIES. PMID- 17734410 TI - OCCURRENCE OF YELLOW LEAF RUST OF WHEAT (PUCCINIA GLUMARUM) IN THE SALT LAKE VALLEY, UTAH. PMID- 17734413 TI - IS INHERITANCE MODIFIED BY ACQUIRED CHARACTERS? PMID- 17734412 TI - TUMORS IN PLANTS. PMID- 17734414 TI - ON THE ETIOLOGY OF EPIDEMIC POLIOMYELITIS. PMID- 17734415 TI - HUMAN REMAINS FROM THE PLEISTOCENE OF FLORIDA. PMID- 17734416 TI - THE ANALYSIS OF "DUST" COLLECTED IN A VACUUM CLEANER FROM THE BOOK SHELVES OF THE RENSSELAER POLYTECHNIC INSTITUTE LIBRARY. PMID- 17734417 TI - THE MAINTENANCE OF SCIENTIFIC RESEARCH. PMID- 17734418 TI - HENRY MARION HOWE. PMID- 17734420 TI - THE ORIGIN OF SPECIES. PMID- 17734419 TI - THE SALT LAKE CITY MEETING. PMID- 17734421 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17734422 TI - THE KAIETEUR FALLS. PMID- 17734423 TI - NECTARINA IN TEXAS. PMID- 17734424 TI - MUSEUM PESTS FEEDING ON GLYCERINE JELLY SLIDES. PMID- 17734426 TI - THE HYDROGEN-ION CONCENTRATION OF SOILS AS AFFECTED BY DRYING. PMID- 17734425 TI - A HAPLOID MUTANT IN THE JIMSON WEED, "DATURA STRAMONIUM". PMID- 17734427 TI - THE MASS OF THE ELECTRON AT SLOW VELOCITY. PMID- 17734428 TI - THE AMERICAN PHILOSOPHICAL SOCIETY. PMID- 17734429 TI - New Tools for Research. PMID- 17734430 TI - Series-Aiding Phototube Bridge. PMID- 17734431 TI - National Instrument Conference and Exhibit. PMID- 17734432 TI - RECENT EXPERIMENTS IN AUTOMATIC WRITING. PMID- 17734433 TI - EXTENSION OF UNIVERSITY TEACHING. PMID- 17734434 TI - COLOR-PHOTOGRAPHY. PMID- 17734436 TI - THE LOCUST PLAGUE IN ALGERIA. PMID- 17734435 TI - THE ACTUAL NUMBER OF TUBERCLE BACILLI WHICH MAY BE PRESENT IN TUBERCULOUS SPUTUM. PMID- 17734437 TI - THE EGG-PLANT. PMID- 17734439 TI - VARIETY AND PLANTING OF CORN. PMID- 17734438 TI - THE TRANSANDINE RAILWAY. PMID- 17734441 TI - Immortality in the Light of Modern Dynamics. PMID- 17734440 TI - THE EXPEDITIONS TO GREENLAND. PMID- 17734442 TI - Purified Transfer RNA's. PMID- 17734444 TI - Well-rounded egghead. PMID- 17734443 TI - Eskimos' language links. PMID- 17734445 TI - Japan (III): Industrial Research Struggles to Close the "Gap". PMID- 17734447 TI - Martian mass and Earth-moon mass ratio from coherent s-band tracking of mariners 6 and 7. AB - Range and Doppler tracking data from Mariners 6 and 7 have been used to obtain values for the ratio of the mass of the earth to that of the moon which are in substantial agreement with those determined from other Mariner and Pioneer spacecraft. There is an inconsistency of about 0.004 percent in values for the mass of the moon determined from lunar trajectories. A gravitational constant for Mars of 42,828.48 +/- 1.38 cubic kilometers per second per second, obtained on the basis of data collected during the 5 days prior to the closest approach of Mariner 6 to Mars, is in excellent agreement with the result obtained by Null from tracking data of Mariner 4. PMID- 17734448 TI - Dimethylpropynylbenzamides: a new group of herbicides. AB - N-(1,1-Dimethylpropynyl)-3,5-dichlorobenzamide is representative of a group of benzamides that are herbicidally active on annnual and perennial grasses with potential agricultural uitility in forage legumes, certain turf grasses, and clultivated crops. PMID- 17734449 TI - Prevention of metamorphosis by exposure of insect eggs to juvenile hormone analogs. AB - Metamorphosis of the bugs Pyrrhocoris apterus and Oncopeltus fasciatus is blocked by the application of juvenile hormone analogs to the eqgs 4 weeks earlier. One or more supernumerary larval molts occur to form "giant" larvae which routinely die without undergoing netamorphosis. When the corpora allatta were excised at the outset of the fifth larval stage, the entire phenomenon vanished and all individuals underwent normal metamorphosis. The inhibition of metamorphosis can therefoore be attributed to a continuation of the secretion of endogenous juvenile hormone by the corpora allata of mature larvae deried from eggs treated with juvenile hormone. PMID- 17734450 TI - Control of form in cells. PMID- 17734451 TI - Cross-reactions of oncogenic viruses. PMID- 17734452 TI - A RETROSPECT. PMID- 17734454 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17734453 TI - THE ANDES IN NORTHERN PERU. PMID- 17734455 TI - PLANT LICE AND LIGHT EXPOSURE. PMID- 17734456 TI - ON THE MODEL OF THE HELIUM ATOM. PMID- 17734457 TI - THE SANTA BARBARA SKULL. PMID- 17734458 TI - SOME EFFECTS OF INSULIN AND GLUCOKININ ON MAIZE SEEDLINGS. PMID- 17734459 TI - "VITAMIN A" DEFICIENCY IN POULTRY. PMID- 17734460 TI - CHEMISTRY AND MODERN LIFE. PMID- 17734461 TI - SOME ASPECTS OF THE RELATION OF SPECIES TO THEIR ENVIRONMENT. PMID- 17734463 TI - JACOB ROSENBLOOM. PMID- 17734462 TI - GRANTS IN SUPPORT OF RESEARCH. PMID- 17734464 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17734466 TI - PECULIAR HAIL. PMID- 17734465 TI - THE UNITY OF ENGLISH WEIGHTS. PMID- 17734467 TI - THE PROFESSOR AND HIS WAGES. PMID- 17734468 TI - THE NEW YORK STATE FORESTS. PMID- 17734469 TI - A WARNING TO MICROSCOPE USERS. PMID- 17734470 TI - ORGANIC CHEMICAL TRANSFORMATIONS. PMID- 17734471 TI - A SATISFACTORY RATION FOR STOCK RATS. PMID- 17734473 TI - THE OPTICAL SOCIETY OF AMERICA. PMID- 17734472 TI - ALKALOIDAL CONTENT OF DATURAS AFFECTED BY MOSAIC INJURY. PMID- 17734475 TI - THE GEOLOGICAL SOCIETY OF AMERICA. PMID- 17734476 TI - THE AMERICAIN BREEDERS' ASSOCIATION. PMID- 17734474 TI - ANTHROPOLOGY AT THE CHICAGO MEETING. PMID- 17734478 TI - THE GEOLOGICAL SOCIETY OF WASHINGTON. PMID- 17734477 TI - INLAND WATERWAYS. PMID- 17734479 TI - THE DISTRIBUTION OF CLOSELY ALLIED SPECIES. PMID- 17734480 TI - CARBOHYDRATE METABOLISM. PMID- 17734481 TI - BOTANICAL NOTES. PMID- 17734482 TI - THE AMERICAN NATURE-STUDY SOCIETY. PMID- 17734483 TI - Cancer Chemotherapy Program. PMID- 17734484 TI - NAWAPA. PMID- 17734486 TI - Biologists' View of Mars. PMID- 17734487 TI - Completion of the Yellow Triplet of the Monopoly Map. PMID- 17734485 TI - Population Control: Births, Deaths, and Statistical Inference. PMID- 17734488 TI - Shutterbugs. PMID- 17734489 TI - Adoption of the Metric System. PMID- 17734490 TI - Death of a Project. PMID- 17734491 TI - Antibody Induction and Tolerance. PMID- 17734492 TI - Scientific Policy in Britain. PMID- 17734493 TI - Congress: A Higher Education Bill Is Considered a Likely Prospect, But Hard Bargaining Lies Ahead. PMID- 17734494 TI - The Doctors' Debate: What To Do When Medicare Comes Is Main Topic at Stormy AMA Session. PMID- 17734495 TI - Precambrian Glaciated Surface Beneath the Gowganda Formation, Lake Timagami, Ontario. AB - Glacial deposition of the Gowganda formation is established by the discovery of an extensive, well-marked, glaciated, basal contact surface. This surface is exposed near the southeastern end of Lake Timagami, northern Ontario. The Precambrian ice sheet advanced three times from the northeast over the area. PMID- 17734496 TI - Hexamethylenetetramine Hexahydrate: A New Type of Clathrate Hydrate. AB - Hexamethylenetetramine hexahydrate has a three-dimensional framework structure of hydrogen-bonded water molecules. Each hexamethylenetetramine molecule is located in a cavity within this framework but is linked to the water structure by hydrogen-bonds through three of its four nitrogen atoms. PMID- 17734497 TI - Mineralogy of Particulate Matter Suspended in Sea Water. AB - X-ray diffraction analysis of the particulate matter of water samples from the Caribbean Sea, one from the surface and one from a depth of 768 meters, shows that the material has a mineral composition comparable to that found in deep-sea sediments of the area. The minerals found in the water samples include illite, the most abundant clay; kaolinite; chlorite; talc; mixed-layer clay; quartz; feldspar; and amphibole. Kaolinite and chlorite are more abundant relative to illite in the sediments than in the suspended material. PMID- 17734498 TI - Shell Structure of Recent Articulate Brachiopoda. AB - Replicas of the etched surfaces of the brachial valves of Gryphus stearnsi (Dall and Pilsbry) and Pictothyris picta (Dillwyn) were examined by electron microscopy. This method clearly reveals the crystalline texture of two of the morphologic layers of the shells and demonstrates that the calcite crystals accommodate the tubular punctate structures. These findings may be useful in resolving some of the problems of brachiopod taxonomy. PMID- 17734499 TI - Actinomycin D Inhibition of Vitamin D Action. AB - Injection of actinomycin D into rats completely prevents both the rise in serum calcium normally induced by vitamin D and the increased transport of calcium by everted intestinal sacs. Injection of excess parathyroid hormone did not alter this result; this eliminates the possibility that the inhibition of vitamin action was due to blocked hormone synthesis. As a result of these findings, a hypothesis concerning the mechanism of action of vitamin D is presented. PMID- 17734501 TI - Ribosomal-RNA Synthesis in the Absence of Ribosome Synthesis in Germinating Cotton Seeds. AB - Cotton embryos after 72 hours of germination synthesize ribosomal RNA that does not become incorporated into ribosomes and that is very stable. This RNA has many characteristics similar to those of newly synthesized ribosomal RNA of bacteria. PMID- 17734502 TI - 3,4-Dichlorobenzyl Methylcarbamate and Related Compounds as Herbicides. AB - 3,4-Dichlorobenzyl methylcarbainate is a selective preemergence herbicide active against both grass and broadleaf weeds. Synthesis of pigment is inhibited in species sensitive to this chemical. Minor structural modifications, such as positioning of the chlorine on the phenyl ring or variations in the N substituent, significantly alter its activity. PMID- 17734500 TI - Red-Light Thresholds in Heterozygote Carriers of Protanopia: Genetic Implications. AB - Absolute thresholds in response to red light were compared in nine normal subjects, six female carriers of protanopia (heterozygotes), and six male subjects with protanopia. The fovea and four peripheral retinal areas were tested, and all data were obtained before the occurrence of the rod-cone break. Elevated thresholds were found in all retinal areas tested in protanopic males, at the fovea in all carriers, and in some peripheral retinal areas in two carriers. The thresholds for carriers were far below those for the protanopic males, and no greater variability of threshold was found in the carriers when they were compared with the normal control group. The findings do not substantiate the occurrence of inactivation at the locus on the X chromosome for protanopia. PMID- 17734503 TI - Carboxyhemoglobin: Hemodynamic and Respiratory Responses to Small Concentrations. AB - Hemodynamic and respiratory measurements were made on humans before and after inhalation of sufficient carbon monoxide to raise the carboxyhemoglobin to between 5 and 10 percent of saturation. Arterial and mixed-venous oxygen tensions decreased on average 7.3 and 13.3 percent, respectively. One of five subjects devel oped evidence of mild left-ventricular dysfunction. PMID- 17734504 TI - Pox Pottery: Earliest Identified Mexican Ceramic. AB - The earliest known ceramics from Mexico, termed "Pox Pottery," may mark the transition from a nomadic to a settled way of life. The presence of "Pox Pottery" in both coastal Guerrero and the Tehuacan Valley might provide evidence as to the type of environment in which this change first occurred. PMID- 17734505 TI - Glutamic-Oxaloacetic Transaminases in Reticulocytes and Erythrocytes. AB - In rabbits, mature erythrocytes contain only the anionic isozyme of glutamic oxaloacetic transaminase. Reticulocytosis induced by massive bleeding or by treatment with acetylphenylhydrazine is characterized by a five- to sixfold increase in red-cell transaminase and the appearance of a cationic transaminase isozyme that apparently resides in the mitochondrial fraction of reticulocytes. PMID- 17734506 TI - Bacteria as an Indicator of Formation of Antibodies by Single Spleen Cells in Agar. AB - Bacteria can be used to measure the formation of specific antibody by suspensions of single spleen cells. The technique, based on localized immune lysis (plaque formation) in agar, permits assays on the kinetics of increase in the number of cells forming bactericidal antibody in the spleen of immunized mice. The procedure also is useful for testing nonspecific stimulation of antibody synthesis and for analyzing spleen cell populations from donors that have been immunized simultaneously with bacterial and red blood cell antigens. PMID- 17734507 TI - Induced Hypersensitivity to Cold. AB - Extreme hypersensitivity to cold can be induced in the rat by a single subcutaneous injection of carrageenin. In animals so treated, exposure to cold induces necrotizing thrombohemorrhagic lesions in the nose, paws, and tail, accompanied by renal lesions resembling those of the generalized Sanarelli Shwartzman phenomenon. The same treatment elicits hemorrhagic necroses of transplants of Murphy lymphosarcomas in rats. PMID- 17734508 TI - Phytotoxin Isolated from Liquid Cultures of Ceratocystis ulmi. AB - Phytotoxic material has been isolated from liquid cultures of Ceratocystis ulmi. One component of the material has been obtained in pure form and has proved to be a rather thermostable glycoprotein. This compound induced disease symptoms, similar to those produced by the fungus itself, in elm sprouits and trees. PMID- 17734509 TI - Oxidation of Dimethyl Sulfoxide to Dimethyl Sulfone in the Rabbit. AB - A white, crystalline compound was obtained from a butanol extract of the urine of rabbits injected subcutaneously with dimethyl sulfoxide. The melting point and infrared spectrum of the compound were identical with those of authentic dimethyl sulfone. PMID- 17734510 TI - Cradleboard Hoods, Not Corsets. AB - Utmost caution should be exercised in interpreting archeological data out of context. Certain artifacts described in the literature on human paleopathology as therapeutic corsets are in fact hoods for cradleboards. Close cooperation among specialists in various disciplines is desirable in reconstructing aspects of prehistoric culture. PMID- 17734511 TI - Faraday Society Discussion: Proton Transfer Processes. PMID- 17734512 TI - Mathematical Sciences. PMID- 17734514 TI - THE AMERICAN SOCIETY OF NATURALISTS HOMO SCIENTIFICUS AMERICANUS. PMID- 17734513 TI - Forthcoming Events. PMID- 17734515 TI - HOW CAN ENDOWMENTS BE USED MOST EFFECTIVELY FOR SCIENTIFIC RESEARCHE. PMID- 17734516 TI - BIOMETRY AND BIOMETRIKA. PMID- 17734517 TI - THE OCCURRENCE OF THREE INTERESTING FISHES ON THE NEW JERSEY COAST. PMID- 17734518 TI - THE IMPROVEMENT OF THE MEETINGS OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17734519 TI - A RARE SCIENTIFIC BOOK. PMID- 17734520 TI - THE DESTRUCTION OF FROGS. PMID- 17734521 TI - BIGELOW'S BAROMETRY. PMID- 17734522 TI - SCIENTIFIC POSITIONS UNDER THE GOVERNMENT. PMID- 17734523 TI - SECTION B--PHYSICS. PMID- 17734524 TI - INHERITANCE OF THE BELT IN HAMPSHIRE SWINE. PMID- 17734526 TI - DELAYING THE BLOSSOMING OF PEACH TREES BY ETHERIZATION. PMID- 17734525 TI - WING VEINS OF INSECTS. PMID- 17734527 TI - THE ASSOCIATED PRESS AND NEWSPAPER SCIENCE. PMID- 17734528 TI - THE UNIVERSITY OF MAINE AND THE STATE LEGISLATURE. PMID- 17734529 TI - AN ILLINOIS STATE ACADEMY OF SCIENCES. PMID- 17734530 TI - THE FIRST SPECIES RULE FOR DETERMINING TYPES OF GENERA--HOW IT WORKS IN ORNITHOLOGY. PMID- 17734531 TI - CUMULUS CLOUDS OVER THE SAN FRANCISCO FIRE. PMID- 17734533 TI - THE INLAND WATERWAYS COMMISSION. PMID- 17734532 TI - THE SHALER MEMORIAL FUND. PMID- 17734535 TI - THE RELATION BETWEEN PHYSICAL AND MENTAL DEVELOPMENT. PMID- 17734534 TI - PROCESSES OF ORGANIC EVOLUTION. PMID- 17734536 TI - SAMUEL HENSHAW. PMID- 17734537 TI - THE ZOOLOGICAL EXPEDITION TO THE GALAPAGOS ISLANDS OF THE FIELD MUSEUM. PMID- 17734538 TI - THE PACIFIC EXPEDITION OF THE AMERICAN MUSEUM OF NATURAL HISTORY. PMID- 17734539 TI - THE COMMONWEALTH SOLAR OBSERVATORY, CANBERRA. PMID- 17734540 TI - APPOINTMENTS, PROMOTIONS AND RETIREMENTS AT THE MASSACHUSETTS INSTITUTE OF TECHNOLOGY. PMID- 17734541 TI - THE AMERICAN MEDICAL ASSOCIATION AND THE ANTI-TRUST LAW. PMID- 17734542 TI - VOLATILITY OF N1-ACYLSULFANILAMIDES WITH STEAM. PMID- 17734543 TI - THE DECREASE IN VASCULARITY OF HUMAN HEARTS AND KIDNEYS BETWEEN THE THIRD AND SIXTH DECADES. PMID- 17734544 TI - A PROPHECY FULFILLED. PMID- 17734545 TI - AVAILABILITY OF CHEMICALS NOT SOLD COMMERCIALLY. PMID- 17734546 TI - THE NATIONAL DEFENSE RESEARCH COMMITTEE. PMID- 17734547 TI - SAPROPHYTES ANTAGONISTIC TO PHYTOPATHOGENIC AND OTHER MICROORGANISMS. PMID- 17734548 TI - HEMOGLOBIN REGENERATION IN ANEMIC TROUT FED LIVER FRACTIONS AND FLY MAGGOTS. PMID- 17734550 TI - THE NEW ELECTRON MICROSCOPE. PMID- 17734549 TI - A NOTE ON SERUM CHOLINESTERASE VARIABILITY IN MALE AND FEMALE RATS. AB - (1) The serum cholinesterase activity of mature female rats is three to five times as great as that found in mature male rats. Mice sera exhibit similar sexual variations in activity, but to a lesser degree. (2) Immature female rats and probably senile female rats possess a low serum cholinesterase activity, in the same range as that of the mature male rats. PMID- 17734551 TI - A SENSITIVE COLOR REACTION FOR 2-METHYL-1-4-NAPHTHOQUINONE AND RELATED COMPOUNDS. PMID- 17734552 TI - SECTION B, PHYSICS. PMID- 17734553 TI - SECTION G, BOTANY. PMID- 17734554 TI - MEMBERSHIP OF THE AMERICAN ASSOCIATION. PMID- 17734556 TI - AN INSTITUTE FOR BIBLIOGRAPHICAL RESEARCH. PMID- 17734555 TI - ADDRESS OF THE PRESIDENT OF THE ANTHROPOLOGICAL SECTION OF THE BRITISH ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17734557 TI - DISCORD. PMID- 17734559 TI - A CORRECTION. PMID- 17734558 TI - CURRENT NOTES ON PHYSIOGRAPHY. PMID- 17734560 TI - THE PHYLOGENY OF THE TOOTHED WHALES. PMID- 17734561 TI - ANTHROPOLOGY AT THE UNIVERSITY OF CALIFORNIA. PMID- 17734562 TI - Three Annual Reports. PMID- 17734563 TI - Biological Processes in the Formation of Wood. PMID- 17734564 TI - Time Course of Fixation of N2 by Excised Soybean Nodules. PMID- 17734566 TI - A Saliva Test for Prenatal Sex Determination. PMID- 17734565 TI - Influence of Cobalt on Reproduction of Mice and Rats. PMID- 17734567 TI - The Szilard-Chalmers Process in Solid Phosphorus Salts. PMID- 17734568 TI - Some New Coordination Compounds of Thallium. PMID- 17734569 TI - Closed Technique for Collection and Storage of Aliquots of Blood. PMID- 17734570 TI - Effects of High-Voltage Cathode-Ray Irradiation on Cottonseed. PMID- 17734571 TI - Influence of Nutrition upon Appearance of Tumors in Tu50j Stock of D. melanogaster. PMID- 17734573 TI - ENGINEERING PROGRESS AND THE SOCIAL ORDER. PMID- 17734574 TI - FRANCIS HOBART HERRICK. PMID- 17734572 TI - Prolongation of Blood Clotting Time in the Dormant Hamster. PMID- 17734576 TI - MEETING OF THE INDUSTRIAL RESEARCH INSTITUTE. PMID- 17734575 TI - MARY VAUX WALCOTT. PMID- 17734577 TI - CHANGES IN MEDICAL PRESCRIBING IN GREAT BRITAIN. PMID- 17734578 TI - ELECTION OF OFFICERS OF THE AMERICAN CHEMICAL SOCIETY. PMID- 17734579 TI - "UNLIMITED HORIZONS" A WEEKLY BROADCAST. PMID- 17734580 TI - SOME ADDITIONAL OBSERVATIONS ON SLUMPING AND GULLY FORMATION. PMID- 17734581 TI - MATING AND OVIPOSITION IN THE PACIFIC COAST TREE TOAD. PMID- 17734582 TI - SAT-CHROMOSOMES. PMID- 17734584 TI - ON THE INTERDEPENDENCE OF RESPIRATION AND GLYCOLYSIS. PMID- 17734583 TI - THE PROPOSED TERMS "EXERGONIC" AND "ENDERGONIC" FOR THERMODYNAMICS. PMID- 17734585 TI - APPEARANCE OF SKELETAL ABNORMALITIES IN THE OFFSPRING OF RATS REARED ON A DEFICIENT DIET. PMID- 17734586 TI - THE NATURE OF THE ANTI-ALOPECIA FACTOR. PMID- 17734588 TI - A NEW TYPE OF SHIELDED GLASS ELECTRODE. PMID- 17734587 TI - MODIFICATION OF THE CHEMISTRY AND PHARMACOLOGICAL ACTION OF THE CARDIAC GLYCOSIDES. PMID- 17734589 TI - A DIRECT METHOD OF DETERMINING THE ERYTHROCYTE, LEUCOCYTE AND THROMBOCYTE COUNT OF FOWL BLOOD. PMID- 17734591 TI - RECENT PROGRESS IN MALACOLOGY. PMID- 17734590 TI - THE DEBT OF THE WORLD TO PURE SCIENCE. PMID- 17734592 TI - ON THE LAW OF ANCESTRAL HEREDITY. PMID- 17734593 TI - THE ROYAL SOCIETY'S ANTARCTIC CONFERENCE. PMID- 17734594 TI - ELLIS'S NORTH AMERICAN FUNGI. PMID- 17734596 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17734595 TI - NOTES ON INORGANIC CHEMISTRY. PMID- 17734597 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17734598 TI - DISCUSSION AND CORRESPONDENCE. PMID- 17734599 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17734600 TI - THE NORTHERN DURCHMUSTERUNG. PMID- 17734601 TI - SCIENTIFIC JOURNALS. PMID- 17734602 TI - ISOSTASY AND THE SIZE AND SHAPE OF THE EARTH. PMID- 17734603 TI - SAFEGUARDING THE HEALTH OF COLLEGE STUDENTS. PMID- 17734605 TI - STANFORD UNIVERSITY. PMID- 17734604 TI - THE GOVERNMENT OF LEARNED SOCIETIES. PMID- 17734606 TI - THE GEORGE WASHINGTON MEMORIAL. PMID- 17734607 TI - FOREIGN STUDENTS AT AMERICAN COLLEGES AND UNIVERSITIES. PMID- 17734608 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17734609 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17734610 TI - A NOTE ON THE ACCESSORY CHROMOSOMES OF MAN. PMID- 17734611 TI - MORAL AND RELIGIOUS TRAINING IN A STATE UNIVERSITY. PMID- 17734612 TI - INVESTIGATIONS IN THE ATLANTIC OCEAN. PMID- 17734613 TI - THE POOR NITRIFYING POWER OF SOILS A POSSIBLE CAUSE OF "DIE-BACK" (EXANTHEMA) IN LEMONS. PMID- 17734614 TI - THE WATER CONTENT OF THE EMBRYONIC NERVOUS SYSTEM. PMID- 17734615 TI - CONFERENCE ON INDIVIDUAL PSYCHOLOGY. PMID- 17734616 TI - Hepatitis research. PMID- 17734617 TI - How much is enough? PMID- 17734618 TI - Appeal for Mars data. PMID- 17734619 TI - Assessing the demand for scientists and engineers. PMID- 17734620 TI - Stratospheric ozone depletion and solar ultraviolet radiation on Earth. PMID- 17734621 TI - Presidential science advising. PMID- 17734622 TI - Biomedical research: would special presidential advisers help? PMID- 17734624 TI - Bottle-feeding: adverse effects of a Western technology. PMID- 17734623 TI - Biomedical research is good for the economy. PMID- 17734625 TI - DOD Said to Admit to Weather War. PMID- 17734626 TI - Metrication: craft unions seek to block conversion bill. PMID- 17734628 TI - House, senate differ on solar energy. PMID- 17734627 TI - Academy sued on closed meetings. PMID- 17734629 TI - Theoretical physics: speculations on abnormal nuclear matter. PMID- 17734630 TI - Lac system: new research on how a protein binds to DNA. PMID- 17734631 TI - Barrier island forest ecosystem: role of meteorologic nutrient inputs. AB - The Sunken Forest, located on Fire Island, a barrier island in the Atlantic Ocean off Long Island, New York, is an ecosystem in which most of the basic cation input is in the form of salt spray. This meteorologic input is sufficient to compensate for the lack of certain nutrients in the highly weathered sandy soils. In other ecosystems these nutrients are generally supplied by weathering of soil particles. The compensatory effect of meteorologic input allows for primary production rates in the Sunken Forest similar to those of inland temperate forests. PMID- 17734632 TI - Radiohalos in a radiochronological and cosmological perspective. AB - New photographic evidence, data on halo ring sizes, and x-ray fluorescence analyses provide unambiguous evidence that polonium halos exist as a separate and distinct class apart from uranium halos. Because of the short half-lives of the polonium isotopes involved, it is not clear how polonium halos may be explained on the basis of currently accepted cosmological models of Earth formation. PMID- 17734633 TI - Respiration of Benthopelagic Fishes: In situ Measurements at 1230 Meters. AB - The respiration rate in situ of two common benthopelagic fishes, Coryphaenoides acrolepis and Eptatretus deani, was monitored at 1230 meters in the San Diego Trough. The respiration rate of C. acrolepis was two orders of magnitude lower and that of E. deani was significantly lower (P < .05) than rates in comparable shallow-water species. PMID- 17734634 TI - North Carolina glacier: evidence disputed. PMID- 17734635 TI - Structure of silica glass. PMID- 17734636 TI - THE PREVENTION OF THE POLLUTION OF STREAMS BY MODERN METHODS OF SEWAGE TREATMENT. PMID- 17734637 TI - PHYSICS AT THE PITTSBURGH MEETING OF THE AMERICAN ASSOCIATION. PMID- 17734638 TI - THE SOCIETY FOR THE PROMOTION OF ENGINEERING EDUCATION. PMID- 17734639 TI - ASSOCIATION OF ECONOMIC ENTOMOLOGISTS. PMID- 17734640 TI - IRIDESCENT CLOUDS. PMID- 17734641 TI - PEAR BLIGHT IN CALIFORNIA. PMID- 17734642 TI - THE ARC OF QUITO. PMID- 17734643 TI - A FOSSIL MAN FROM KANSAS. PMID- 17734644 TI - PALEONTOLOGY AT THE AMERICAN MUSEUM OF NATURAL HISTORY. PMID- 17734646 TI - The Science Training Group in the Washington Area. PMID- 17734645 TI - Research and Medical Practice. PMID- 17734647 TI - Effect of Rubber Tubing Upon the Stability of Penicillin and Streptomycin Solutions. PMID- 17734648 TI - The Infectiousness of Coccidioidomycosis. PMID- 17734649 TI - Comparative Toxicity of DDT and Four Analogues to Goldfish, Gambusia, and Culex Larvae. PMID- 17734650 TI - A Color Reaction Given by Streptomycin. PMID- 17734651 TI - Relation of Vapor-Pressure Deficit to Evaporation From a Spherical Atmometer in an Air-conditioned Room. PMID- 17734652 TI - A Simple, Rapid Technique for the Study of the Action of Hydrolytic Enzymes on Insoluble Substrates. AB - A rapid, simple, quantitative technique has been developed for the study of the action of hydrolytic enzymes on certain insoluble substrates. The end point of digestion is indicated by the release of a glass bead, when two pieces of lens paper sealed together by the substrate separate due to its digestion by the enzyme. PMID- 17734653 TI - Method for Making Filters Transmitting the Near Ultraviolet and Absorbing Visual Light. PMID- 17734654 TI - Some Notes on the Cancer Problem. PMID- 17734655 TI - Injection vs. Oral Administration of Folic Acid in the Chick. PMID- 17734656 TI - On the Theory of Acids and Bases. PMID- 17734657 TI - Messages from mount olympus. PMID- 17734658 TI - Italy: overwhelmed universities. PMID- 17734660 TI - Letter to the editor. PMID- 17734661 TI - Introducing william bevan. PMID- 17734659 TI - Soviet synthesis of element 105. PMID- 17734662 TI - Living polymers: a tool in studies of ions and ion-pairs. AB - Studies of living polymers have greatly enriched our knowledge of the behavior of ions and ion-pairs in organic media. Future investigations will lead to more detailed knowledge of these interesting species. Especially, intramolecular associations or intramolecular solvation by the polymer chains provide promising field for additional studies, and one example of such phenomena was reported recently by Fisher and Szwarc (42). PMID- 17734663 TI - Millimeter-Wavelength Radio Systems: Use of millimeter wavelengths for radio systems may alleviate crowding at lower frequencies. PMID- 17734664 TI - Academy may study defoliation. PMID- 17734665 TI - "Men of science" forthcoming. PMID- 17734666 TI - Congress: Some Progress toward Putting House in Order. PMID- 17734667 TI - Academic protocol: from the g. Swinger manual. PMID- 17734669 TI - Surface films compacted by moving water: demarcation lines reveal film edges. AB - When water flows under the edge of a surface film the large viscous shear stress at the edge prevents the film from spreading and raises a ridge on the water surface. Near the top of its downstream flank the ridge has an abrupt change in curvature that we see as a line on the water. PMID- 17734668 TI - Brines and interstitial brackish water in drill cores from the deep gulf of Mexico. AB - Marked increases in interstitial salinity occur in two drill holes located in the Gulf of Mexico at a water depth of more than 3500 meters. The increases probably arose through diffusion of salt from buried evaporites. In one hole, however, brackish water was encountered on penetrating the oil-permeated cap rock of a salt dome. The phenomenon is attributed to production of fresh water during oxidation of petroleum hydrocarbons and decomposition of gypsum to form native sulfur. PMID- 17734670 TI - Planetary albedo changes due to aerosols. AB - Absorption and scattering by aerosols and reflection of solar radiation from the surface determine the sign of the change in the planetary albedo caused by the presence of aerosols. This change in planetary albedo results in atmospheric heating or cooling. Small changes in the ratio of absorption to scattering over time can reverse such heating or cooling trends. PMID- 17734671 TI - Bocono fault, venezuelan andes: evidence of postglacial movement. AB - Postglacial, right-lateral, strike-slip movement along the Bocono fault, measured on detailed topographic maps, averages 66 meters. The rate of movement was approximately 0.66 centimeter per year, as indicated by carbon-14 dating of associated soil. This evidence suggests that postglacial movement between the Caribbean and Americas plates occurred mainly along the Bocono fault and the north coast of Venezuela. PMID- 17734672 TI - Obsidian hydration rates. PMID- 17734673 TI - Tours AAAS Annual Meeting 26-31 December 1970 Chicago. PMID- 17734674 TI - THE GOVERNMENT AS A PUBLISHING HOUSE. PMID- 17734675 TI - THE NATIONAL RAILWAY EXPOSITION.--II. PMID- 17734676 TI - THE WEATHER IN MAY, 1883. PMID- 17734677 TI - SYMMETRICAL LINEAR FIGURES PRODUCED BY REFLECTION ALONG A RIVER-BANK. PMID- 17734678 TI - THE AMERICAN SWAMP CYPRESS. PMID- 17734679 TI - RECENT BABYLONIAN RESEARCH. PMID- 17734680 TI - OCEAN WATER AND BOTTOMS. PMID- 17734681 TI - THE INTELLIGENCE OF THE AMERICAN TURRET SPIDER. PMID- 17734682 TI - THE NATURAL HISTORY OF IMPLEMENTS. PMID- 17734684 TI - Equations of third degree. PMID- 17734683 TI - Solar constant. PMID- 17734685 TI - WARD'S DYNAMIC SOCIOLOGY. PMID- 17734686 TI - GEOLOGY OF SOUTHERN PENNSYLVANIA. PMID- 17734687 TI - INTELLIGENCE FROM AMERICAN SCIENTIFIC STATIONS. PMID- 17734688 TI - This week in science. PMID- 17734689 TI - The molecule of the year. PMID- 17734690 TI - In reply: carcinogens and human health: part 1. PMID- 17734692 TI - The avocado illusion. PMID- 17734691 TI - Erratum. AB - In the Erratum (7 Dec., p. 1320) about the Editors' response to George Legge's letter of 16 November (p. 889), the error was not corrected. Reference should have been made to a "300-nm beam spot," not a "300-microm beam spot." PMID- 17734693 TI - Choosing Detectors for the SSC: SSC officials are inching toward choosing the two large-scale experiments that will be done in the machine--a decision that will influence physics for at least a decade. PMID- 17734695 TI - A rare view of the moon. PMID- 17734694 TI - Stanford sails into a storm. PMID- 17734696 TI - Plus ca Change .. PMID- 17734697 TI - Space Program: Blueprint for Ambiguity?: A national commission's report may lead to major reforms at NASA, but some experts aren't so sure. PMID- 17734698 TI - Blood, money, and the pentagon. PMID- 17734699 TI - Astro-1: from the jaws of defeat. PMID- 17734701 TI - What next for the energy labs? PMID- 17734700 TI - Volcanoes: Old, New and--Perhaps--Yet To Be. PMID- 17734702 TI - Gazing through a gravitational lens. PMID- 17734703 TI - Natchez man gets younger. PMID- 17734704 TI - NSF Watchdog Plays Up Misconduct. PMID- 17734706 TI - AAAS--Newcomb Cleveland Prize. PMID- 17734705 TI - Biomass burning in the tropics: impact on atmospheric chemistry and biogeochemical cycles. AB - Biomass burning is widespread, especially in the tropics. It serves to clear land for shifting cultivation, to convert forests to agricultural and pastoral lands, and to remove dry vegetation in order to promote agricultural productivity and the growth of higher yield grasses. Furthermore, much agricultural waste and fuel wood is being combusted, particularly in developing countries. Biomass containing 2 to 5 petagrams of carbon is burned annually (1 petagram = 10(15) grams), producing large amounts of trace gases and aerosol particles that play important roles in atmospheric chemistry and climate. Emissions of carbon monoxide and methane by biomass burning affect the oxidation efficiency of the atmosphere by reacting with hydroxyl radicals, and emissions of nitric oxide and hydrocarbons lead to high ozone concentrations in the tropics during the dry season. Large quantities of smoke particles are produced as well, and these can serve as cloud condensation nuclei. These particles may thus substantially influence cloud microphysical and optical properties, an effect that could have repercussions for the radiation budget and the hydrological cycle in the tropics. Widespread burning may also disturb biogeochemical cycles, especially that of nitrogen. About 50 percent of the nitrogen in the biomass fuel can be released as molecular nitrogen. This pyrdenitrification process causes a sizable loss of fixed nitrogen in tropical ecosystems, in the range of 10 to 20 teragrams per year (1 teragram = 10(12) grams). PMID- 17734707 TI - Kinematics of late paleozoic continental collision between laurentia and gondwana. AB - In the Appalachians, late Paleozoic Alleghanian orogenesis is widely regarded as resulting from dextral oblique collision between irregular margins of Gondwana and Laurentia. However, this relative plate motion cannot account for coeval convergence in the Ouachitas and Variscides and is incompatible with some tectonic transport indicators in the Appalachians. An alternative kinematic model is proposed in which early sinistral transpression in the Appalachians is followed by counterclockwise rotation of Gondwana and the development of a system of dextral strike-slip faults extending from southern Europe to Alabama. PMID- 17734708 TI - Control of a desert-grassland transition by a keystone rodent guild. AB - Twelve years after three species of kangaroo rats (Dipodomys spp.) were removed from plots of Chihuahuan Desert shrub habitat, density of tall perennial and annual grasses had increased approximately threefold and rodent species typical of arid grassland had colonized. These were just the most recent and drmatic in a series of changes in plants and animals caused by experimental exclusion of Dipodomys. In this ecosystem kangaroo rats are a keystone guild: through seed predation and soil disturbance they have major effects on biological diversity and biogeochemical processes. PMID- 17734709 TI - Forensic Scientists Uncovering Fate of Brazil's "Disappeared" with Help of AAAS. PMID- 17734710 TI - Robert nansen. PMID- 17734711 TI - Spotlight on top scientists in Africa. PMID- 17734713 TI - Global warming: not only show in town. PMID- 17734712 TI - Fellows Sought from Industry for OSTP Posts. PMID- 17734714 TI - Interview with ivan havel: science in eastern europe. PMID- 17734717 TI - Moments In the Life of a Scientist. Bruno Rossi. Cambridge University Press, New York, 1990. xvi, 181 pp., illus., + plates. $44.50. PMID- 17734715 TI - The High-Status Track. Studies of Elite Schools and Stratification. Paul William Kingston and Lionel S. Lewis, Eds. State University of New York Press, Albany, 1990. xxxiv, 261 pp., illus. $54.50; paper, $17.95. SUNY Series, Frontiers in Education. PMID- 17734718 TI - Freedom in Machinery. Vol. 2, Screw Theory Exemplified. Jack Phillips. Cambridge University Press, New York, 1990. xiv, 251 pp., illus. $85. PMID- 17734719 TI - The Mechanics of Earthquakes and Faulting. Christopher H. Scholz. Cambridge University Press, New York, 1990. xii, 439 pp., illus., $79.50. PMID- 17734720 TI - The Astronomer's Universe. Stars, Galaxies, and Cosmos. Herbert Friedman. Norton, New York, 1990. xxii, 359 pp., illus. $24.95. Commonwealth Fund Book Program. PMID- 17734721 TI - Products & materials. PMID- 17734722 TI - The "tenure" problem. PMID- 17734724 TI - Health records. PMID- 17734723 TI - The "tenure" problem. PMID- 17734725 TI - Writing posture and paper orientation. PMID- 17734726 TI - Writing posture and paper orientation. PMID- 17734727 TI - The "tenure" problem. PMID- 17734728 TI - Environmental cancer. PMID- 17734729 TI - Solar energy and electric utilities: should they be interfaced? AB - Analyses of the economics of solar collection in the firm- and shifting-peak cases (that is, with off-peak electricity indefinitely available or with a flat load curve) indicate that, for many important applications, solar energy systems that interface with electric utilities can be justified only in terms of the value of the off-peak utility fuels that they displace. In regions where off-peak electricity costs are low, the most economically efficient solar energy systems will be those that use electricity as the auxiliary energy source. This implies extremely low break-even costs for a number of important solar energy applications. In regions where the cost of off-peak electricity is higher than that of competing energy forms, the most economical solar energy systems will utilize auxiliary fuels other than electricity. The general conclusion is that conventional electric utility systems and most solar energy systems represent a poor technological match. The basic problem is that both technologies are very capital intensive. The electric utility, because of the high fixed costs of generation, transmission, and distribution capacity, represents a poor backup for solar energy systems. On the other hand, the solar collection system, because it represents pure, high-cost capital and because of its outage problems, cannot be considered as a part-load source of auxiliary energy for the electric utility system. PMID- 17734731 TI - Brown on deterrence. AB - Some insight into Secretary of Defense Harold Brown's views on deterrence may be gained from the following excerpts from an address titled "Strategic Force Structure and Strategic Arms Limitations" he delivered at the Institute of U.S. Studies of the Soviet Academy of Science in Moscow in March 1975. PMID- 17734730 TI - Harold brown and defense: from scientist to secretary. PMID- 17734732 TI - Gene-splicing: critics of research get more brickbats than bouquets. PMID- 17734733 TI - Carter going slow on national health insurance. PMID- 17734734 TI - PR Man Helps Select Author of Book on Pollution Case. PMID- 17734735 TI - Legion Fever: "failed" investigation may be successful after all. PMID- 17734736 TI - Analgesia: how the body inhibits pain perception. PMID- 17734737 TI - Superheavy elements: confirmation fails to materialize. PMID- 17734738 TI - Handicapped resource group members work for barrier elimination. PMID- 17734739 TI - Board approves continuation of R & d budget project. PMID- 17734740 TI - AAAS Annual Meeting Notes. PMID- 17734741 TI - Science in colorado: the second century begins. PMID- 17734742 TI - Quandaries for american scholars. PMID- 17734743 TI - Extragalactic astronomy. PMID- 17734744 TI - Advances with lasers. PMID- 17734745 TI - Normal motor behavior. PMID- 17734746 TI - Delaware river: evidence for its former extension to wilmington submarine canyon. AB - Seismic-reflection profiles indicate that during the Pleistocene the Delaware River flowed across the continental shelf east of Delaware Bay and emptied into Wilmington Submarine Canyon. The ancestral valley (width, 3 to 8 kilometers; relief, 10 to 30 meters) is buried, is not reflected in the surface topography, and probably predates the formation of the present canyon head. PMID- 17734747 TI - Occultation of egr Geminorum by Mars: Evidence for Atmospheric Tides? AB - Temperature profiles of the martian atmosphere have been derived from airborne observations of the 8 April 1976 occultation of epsilon Geminorum. Within the altitude range from 50 to 90 kilometers, these profiles show peak-to-peak variations of 35 degrees K with a vertical scale of 20 kilometers and represent evidence for strong tides in the martian atmosphere. However, more information is necessary to conclusively rule out a radiative explanation for the temperature variations. PMID- 17734748 TI - AA-AAAS Seeks to Consolidate Atlanta Area AAAS Members. PMID- 17734749 TI - BOTANICAL TEACHING. PMID- 17734751 TI - III. METHODS OF BOTANICAL TEACHING. PMID- 17734750 TI - II. THE PRODUCT OF OUR BOTANICAL TEACHING. PMID- 17734752 TI - DISCUSSION. PMID- 17734753 TI - LEONARD P. KINNICUTT. PMID- 17734754 TI - HENRY PICKERING BOWDITCH. PMID- 17734755 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17734756 TI - THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17734757 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17734759 TI - MUSEUM LABELING. PMID- 17734758 TI - WILKES'S ANTARCTIC DISCOVERIES. PMID- 17734760 TI - FACULTY BUSINESS ACCELERATOR. PMID- 17734761 TI - EXPERIENCES WITH THE GRADING SYSTEM OF THE UNIVERSITY OF MISSOURI. PMID- 17734762 TI - AN EFFICIENT AND RAPID MERCURY STILL. PMID- 17734764 TI - THE FUNCTION AND EFFICIENCY OF THE AGRICULTURAL COLLEGE. PMID- 17734763 TI - THE ASSOCIATION OF AMERICAN GEOGRAPHERS. PMID- 17734765 TI - A STUDY OF RETARDATION IN THE SCHOOLS OF MINNESOTA. PMID- 17734766 TI - AN ANTHROPOLOGICAL SURVEY OF CANADA. PMID- 17734767 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17734768 TI - THE MUSEUM OF ANTHROPOLOGY OF THE UNIVERSITY OF CALIFORNIA. PMID- 17734770 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17734769 TI - THE FRANCIS GALTON LABORATORY FOR NATIONAL EUGENICS. PMID- 17734771 TI - AN EARLY DISCUSSION OF HEREDITY. PMID- 17734772 TI - THE NUMBER OF STUDENTS TO A TEACHER IN STATE COLLEGES AND UNIVERSITIES. PMID- 17734773 TI - NOTE ON THE OHIO PLACODERM DINICHTHYS TERRELLI. PMID- 17734774 TI - THE PROPOSED REFORM OF THE CALENDAR. PMID- 17734775 TI - THE NATIONAL ACADEMY OF SCIENCES. PMID- 17734776 TI - TICK (IXODOIDEA) GENERIC NAMES TO BE INCLUDED IN THE "OFFICIAL LIST OF ZOOLOGICAL NAMES". PMID- 17734777 TI - Letters. PMID- 17734778 TI - Hanford reactors down but not out. PMID- 17734779 TI - Hiroshima after 25 years: "we are all survivors". PMID- 17734780 TI - Carnegie plans telescope in chile. PMID- 17734781 TI - Sound from apollo rockets in space. AB - Low-frequency sound has been recorded on at least two occasions in Bermuda with the passage of Apollo rocket vehicles 188 kilometers aloft. The signals, which are reminiscent of N-waves from sonic booms, are (i) horizontally coherent; (ii) have extremely high (supersonic) trace velocities across the tripartite arrays; (iii) have nearly identical appearance and frequencies; (iv) have essentially identical arrival times after rocket launch; and (v) are the only coherent signals recorded over many hours. These observations seem to establish that the recorded sound comes from the rockets at high elevation. Despite this high elevation, the values of surface pressure appear to be explainable on the basis of a combination of a kinetic theory approach to shock formation in rarefied atmospheres with established gas-dynamics shock theory. PMID- 17734782 TI - Alteration of lunar optical properties: age and composition effects. AB - A model for lunar surface processes is presented which explains the main albedo and color contrasts and the temporal changes in these optical properties. Evidence from Apollo 11 and Apollo 12 samples and telescopic spectral reflectivity measurements indicates that the maria are similar in mineralogy on a regional scale and that the highlands are consistent with an anorthositic-gabbro composition. Bright craters and rays in both regions expose materials that are relatively crystalline compared with their backgrounds, which are richer in dark glass. With age, bright craters and rays in the maria darken in place by meteorite impact-induced vitrification and mixing with the surrounding material. Highland bright craters and rays may, however, darken primarily through regional contamination by iron- and titanium-rich mare material. PMID- 17734783 TI - The last interglacial: paleotemperatures and chronology. AB - The O(18)/O(16) analysis and Th(230)/Pa(231) dating of deep-sea cores showed that the last interglacial age, with an early major temperature maximum followed by two smaller ones, extended from 100,000 to 70,000 years ago and was preceded by a glacial age extending from 120,000 to 100,000 years ago. The O(18)/O(16) analysis and Th(230)/U(234) dating of speleothems confirm and refine these ages. PMID- 17734785 TI - Beyond test score comparisons. PMID- 17734784 TI - Reducing greenhouse gases. PMID- 17734786 TI - Antisense research. PMID- 17734788 TI - This week in science. PMID- 17734787 TI - State key labs in china. PMID- 17734789 TI - Scientific competency through fun. PMID- 17734790 TI - Climatic change and forests. PMID- 17734791 TI - Erratum. AB - Figure 5 (p. 205) of the report "Observation of individual DNA molecules undergoing gel electrophoresis" by Steven B. Smith et al. (13 Jan., p. 203) was printed upside-down. PMID- 17734792 TI - Cost of electricity. PMID- 17734793 TI - Broad training for social scientists. PMID- 17734794 TI - Narrow corridors stop falling soda machines. PMID- 17734795 TI - Landsats: Drifting toward Oblivion?: U.S. "commercial" earth observing satellites may be abandoned in March, creating a gap in coverage that may last until 1991 or later. PMID- 17734796 TI - Sakharov declines to run for moscow seat. PMID- 17734797 TI - Fertile ground for arms control. PMID- 17734798 TI - CBO Lists Options for Cutting R&D. PMID- 17734799 TI - A Global Supercomputer Race for High Stakes: Although U.S. companies currently hold a lead in technology and sales, Japanese manufacturers are now producing fast machines and slashing prices. PMID- 17734800 TI - Arctic Ozone Is Poised for a Fall: An airborne expedition into the Arctic stratosphere found clear evidence that the same cloudmediated chemistry that leads to the Antarctic ozone hole appears over the Arctic. PMID- 17734801 TI - Lift-Off Laser: GaAs on Glass. PMID- 17734802 TI - New look at turtle migration mystery. PMID- 17734803 TI - Keck Telescope Mirror Is in Production: The goal is to turn 36 hexagons of high grade ceramic into a single optical surface 10 meters across; the question is how? PMID- 17734804 TI - Combining cognitive and statistical approaches to survey design. AB - Sample surveys provide data for academic research, government policy-making, the media, and business. Statistical research aims to improve survey data by reducing extraneous sources of variability and thus increasing accuracy. Researchers have begun to use paradigms adapted from the cognitive sciences to study those sources of variability associated with the processes that the respondent undertakes in understanding questions, remembering, judging and estimating, and formulating answers. To generalize laboratory-based findings, researchers must begin to embed designed experiments that vary the questionnaire content into sample surveys of broad population. Issues associated with the design of and statistical inference from such embedded experiments are examined and illustrated with an example on the effects of context questions on responses in attitude surveys. PMID- 17734805 TI - Polymers, fractals, and ceramic materials. AB - Concepts borrowed from polymer science have been applied to tailor the properties of inorganic materials, especially those derived from amorphous precursors. Fractal geometry can be used to characterize macromolecular precursors and to relate their structures to kinetic growth processes. Within the silica system, for example, it is possible to manipulate the conditions of solution polymerization to yield a variety of macromolecules from branched chains to smooth colloidal particles. PMID- 17734806 TI - Chemico-Viscous Remanent Magnetization in the Fe3O4-yFe2O3 System. AB - The chemical remanent magnetization (CRM) acquired when single-domain size magnetite (Fe(3)0(4)) oxidizes to maghemite (gammaFe(2)O(3)) in a 50-microtesla field at a series of 13 temperatures from 1000 to 6560C is of similar intensity to viscous remanent magnetization (VRM) acquired under the same field and temperature conditions by unoxidized magnetite. The remanences of the oxidized and unoxidized phases also have similar resistances to demagnetization. These similarities imply that the remanence of the oxidized material is a chemico viscous remanent magnetization (CVRM) having some of the characteristics of both classic growth CRM and thermally activated VRM. At low temperatures in partially oxidized grains, VRM of the magnetite core and growth CRM of the maghemite surface layer contribute about equally to CVRM. Near the Curie point, intensity of CVRM increases to a Hopkinson-type peak. High-temperature CVRM is more resistant to demagnetization than the thermoremanent magnetization (TRM) produced from cooling through the Curie point. PMID- 17734807 TI - Epitaxial growth of diamond films on si(111) at room temperature by mass-selected low-energy c+ beams. AB - Diamond films ( approximately 0.7 micrometer thick) have been epitaxially grown on Si(111) substrates at room temperature with mass-selected 120-electronvolt C(+) ions. The diamond reflections observed in x-ray diffraction are well localized at their predicted positions, indicating that (i) the diamond(111) and (220) planes are parallel to the Si(111) and (220), respectively; (ii) the diamond rotational spread around its (111) normal is approximately 1.7 degrees ; and (iii) the mosaic block size is approximately 150 A. The film growth is discussed in terms of subplantation-a shallow subsurface implantation model. This discovery is an important step toward diamond semiconductor devices. PMID- 17734808 TI - Atomic resolution imaging of adsorbates on metal surfaces in air: iodine adsorption on pt(111). AB - The adsorption of iodine on platinum single crystals was studied with the scanning tunneling microscope (STM) to define the limits of resolution that can be obtained while imaging in air and to set a target resolution for STM imaging of metal surfaces immersed in an electrochemical cell. Two iodine adlattice unit cells of slightly different iodine packing density were clearly imaged: ( radical7 x radical7) R19.1 degrees -I, surface coverage o(I) = 3/7; and (3 x 3) I, o(I) = 4/9. The three iodine atoms in the ( radical7 x radical7) unit cell form a regular hexagonal lattice interatomic distance d(I) = 0.424 nanometer, with two atoms adsorbed in threefold hollow sites and one atom adsorbed at an atop site. The (3 x 3) unit cell showed two different packing arrangements of the four iodine atoms exit. In one of the (3 x 3) structures, the iodine atoms pack to form a hexagonal lattice, d(I) = 0.417 nanometer, with three of the iodine atoms at twofold adsorption sites and one atom at an atop site. Another packing arrangement of iodine into the (3 x 3) unit cell was imaged in which the iodine atoms are not arranged symmetrically. PMID- 17734810 TI - The culture of objectivity: beamtimes and lifetimes. PMID- 17734811 TI - An industry restructured: divide and prosper. PMID- 17734809 TI - Uranium-series dated authigenic carbonates and acheulian sites in southern egypt. AB - Field investigations in southern Egypt have yielded Acheulian artifacts in situ in authigenic carbonate deposits (CaCO(3)-cemented alluvium) along the edges of nowaggraded paleovalleys (Wadi Arid and Wadi Safsaf). Uranium-series dating of 25 carbonate samples from various localities as far apart as 70 kilometers indicates that widespread carbonate deposition occurred about 45, 141 and 212 ka (thousand years ago). Most of the carbonate appears to have been precipitated from groundwater, which suggests that these three episodes of deposition may be related to late Pleistocene humid climates that facilitated human settlement in this now hyperarid region. Carbonate cements from sediments containing Acheulian artifacts provide a minimum age of 212 ka for early occupation of the paleovalleys. PMID- 17734813 TI - Technology of warfare: the war of invention. PMID- 17734812 TI - Nuclear energy in Canada: nucleus. PMID- 17734814 TI - Products & materials. PMID- 17734815 TI - Competition in the international marketplace. PMID- 17734816 TI - Steering Clear of Sakhalin: Advanced air navigation schemes might prevent another disaster like the one that befell the Korean airliner; Congress promotes Navstar as the solution. PMID- 17734817 TI - A PAC for Star Wars. PMID- 17734818 TI - New CDC Director Is Named. PMID- 17734819 TI - Airliner incident affects soviet--u.s. Exchanges. PMID- 17734820 TI - Reagan gives blessing to federal labs' reforms. PMID- 17734822 TI - Pressure for trauma institute. PMID- 17734821 TI - Study of NIH Gets Under Way: The biomedical research community is feeling hard pressed to defend the traditional organization of basic research against the demands of special interest groups and their congressional supporters. PMID- 17734823 TI - Mixed Marks for Berkeley Materials Center: A DOE panel's recommendations could threaten construction of the synchrotron light source that was to be NCAM's centerpiece. PMID- 17734824 TI - Neptune ring fades again. PMID- 17734825 TI - New Synchrotron Light Sources Sputtering: Murphy's Law, high expectations, and a shortage of funds and accelerator physicists add up to exasperating delays at Brookhaven and Wisconsin. PMID- 17734826 TI - Methane C-h bonds activated. PMID- 17734828 TI - Health and welfare in an industrial era: endangered lives. PMID- 17734827 TI - Industry u.s. And foreign: american industry in international competition. PMID- 17734829 TI - Geomagnetism: The Earth's Core. PMID- 17734830 TI - Seismology: earthquake forecasting and warning. PMID- 17734831 TI - Early eutrophication in the lower great lakes:. AB - New Evidence from Biogenic Silica in Sediments New evidence from studies of biogenic silica and diatoms in sediment cores indicates that eutrophication in the lower Great Lakes resulted from nutrient enrichment associated with early settlement and forest clearance. Diatom production peaked from 1820 to 1850 in Lake Ontario, at about 1880 in Lake Erie, but not until 1970 in Lake Michigan. This is the first reported sediment record of the silica-depletion sequence for the Great Lakes. PMID- 17734832 TI - Tilt and seismicity changes in the shumagin seismic gap. AB - Changes in the ground surface tilt and in the rate of seismicity indicate that an aseismic deformation event may have occurred between 1978 and 1980 along the plate boundary in the eastern Aleutians, Alaska, within the Shumagin seismic gap. Pavlof Volcano was unusually quiescent during this period. The proposed event would cause an increase of stress on the shallow locked portion of the plate boundary, bringing it closer to rupture in a great earthquake. PMID- 17734833 TI - Sulfuric Acid droplet formation and growth in the stratosphere after the 1982 eruption of el chichon. AB - The eruption of El Chichon Volcano in March and April 1982 resulted in the nucleation of large numbers of new sulfuric acid droplets and an increase by nearly an order of magnitude in the size of the preexisting particles in the stratosphere. Nearly 10(7) metric tons of sulfuric acid remained in the stratosphere by the end of 1982, about 40 times as much as was deposited by Mount St. Helens in 1980. PMID- 17734834 TI - Zonal winds in the central equatorial pacific and el nino. AB - Easterly trade winds from near-equatorial islands in the central Pacific weakened before each El Nino between 1950 and 1978, except for the 1963 El Nino. The weakening of the easterlies and their later collapse did not occur uniformly over several months, but rather through a series of strong westerly wind bursts lasting 1 to 3 weeks. The bursts may force equatorial Kelvin waves in the ocean that can both initiate and sustain the sea surface warming characteristics of El Nino events. PMID- 17734835 TI - THE NATIONAL ACADEMY OF SCIENCES. PMID- 17734836 TI - RECENT ADVANCES IN MALACOLOGY. PMID- 17734837 TI - A STUDY OF THE COLON BACILLUS GROUP, AND ESPEVIALLY OF ITS VARIABILITY IN FERMENTING POWER UNDER DIFFERENT CONDITIONS. PMID- 17734838 TI - SUPERHEA TED STEAX IN STEAM ENGINES. PMID- 17734839 TI - ON CERTAIN PHYSICAL DIFFICULTIES IN THE CONSTRUCTION OF LARGE GUNS. PMID- 17734840 TI - OYTOGENIC AND PHYLOGENIC VARIATION. PMID- 17734841 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17734842 TI - NOTES ON INORGANIC CHEMISTRY. PMID- 17734843 TI - ASTRONOMICAL NOTES. PMID- 17734844 TI - AN OPTICAL ILLUSION. PMID- 17734845 TI - LE CONTE'S ELEMENTS OF GEOLOGY. PMID- 17734846 TI - THE AMERICAN GEOLOGIST, NOVEMBER. PMID- 17734847 TI - ENTOMOLOGICAL SOCIETY OF WASHINGTON NOVEMBER 12, 1896. PMID- 17734848 TI - ACADEMY OF NATURAL SCIENCES OF PHILADELPHIA, OCTOBER 27. PMID- 17734850 TI - This week in science. PMID- 17734849 TI - THE ACADEMY OF SCIENCE OF ST. LOUIS. PMID- 17734851 TI - Economic arteriosclerosis and competitiveness. PMID- 17734852 TI - Crisis in systematics. PMID- 17734853 TI - Federal budget. PMID- 17734854 TI - Mesoamerica, not the new world. PMID- 17734855 TI - Perestroika and Detente Boost IIASA's Prospects: The East-West think tank has a grant from the U.S. government and is receiving renewed attention from the Soviet Union. The main priority is to bolster its scientific credibility. PMID- 17734857 TI - Effect of 1986 law still unproven. PMID- 17734858 TI - A Lopsided Look at Evolution: An analysis of the fossil record reveals some unexpected patterns in the origin of major evolutionary innovations, patterns that presumably reflect the operation of different mechanisms. PMID- 17734856 TI - Debate Warming Up on Legal Migration Policy: If domestic fertility levels remain low, immigrants--mainly Asians and Hispanics--will have an ever growing impact on the nation's culture and economy. PMID- 17734859 TI - U.s. Competitiveness: beyond the trade deficit. AB - Large trade deficits and the corresponding increase in U.S. international indebtedness have raised concerns about the long-run competitiveness of the United States. But being competitive requires more than balance in our foreign trade; it requires an improving standard of living. The long-term U.S. competitive problem is largely caused by low saving rates, high costs of capital, and the resulting inadequate level of both visible and invisible investment. As long as the U.S. national saving rate remains far below that of all our major competitor nations, there is little chance for restoring America's international economic position. PMID- 17734860 TI - Components of competitiveness. AB - There are various ways of looking at economic competitiveness. Some of the popular conceptions of America's relative position are clarified by examining the concept in terms of wage cost, productivity, profit margins, and exchange rates. A quantitative approach is laid out and examined in relation to similar measures for other countries. Also some relationships between competitiveness and the external deficit on current account for the United States are analyzed. PMID- 17734861 TI - Technology and competitiveness: a key to the economic future of the United States. AB - The United States still is a leader in technology and innovation, but American industry has been slow to translate that advantage into commercial success. A major contributing factor is the low status accorded manufacturing in this country and a lack of teamwork among scientists, engineers, and managers. However, there are encouraging signs that these key players in the innovation cycle are recognizing the need to work together to improve products and manufacturing processes and to restore the competitive position of the United States. PMID- 17734862 TI - Estimate of electromagnetic quantities in space from ground magnetic records. AB - Magnetic field records at the earth's surface contain the effects of a variety of different source currents flowing in outer space. During the last decade, several computational techniques for the use of magnetometer data have been proposed to obtain the global pattern of the electric fields and currents and Joule heating in the ionosphere. The numerical algorithm has now been enormously improved, such that simultaneous more direct or in situ measurements by satellites and radars can be incorporated into the scheme. In particular, owing to recent progress in satellite-viewed auroral images, it is possible to estimate "instantaneous" patterns of the ionospheric electrodynamic quantities over the entire polar region with a time resolution of several minutes. This report demonstrates that, contrary to our conventional views, large ionospheric currents can flow in regions of low auroral activity. PMID- 17734863 TI - Design of a monomeric arsinogallane and chemical conversion to gallium arsenide. AB - A monomeric arsinogallane containing a covalent gallium-arsenic bond has been prepared, and its molecular structure has been determined by x-ray crystallography. The compound reacted with tert-butanol at ambient temperature to yield the III-V semiconductor gallium arsenide as a finely divided amorphous solid. During the initial stages of the reaction small clusters of gallium arsenide were apparently present in solution. The band gaps of these particles, as observed by their absorption spectra, were larger than that of the bulk material. This work is a step toward the development of new molecular precursors for technologically important materials and the study of quantum size effects in small semiconductor particles. PMID- 17734864 TI - Naturally occurring auxin transport regulators. AB - The process of polar auxin transport, central to a plant's auxin relations, can be inhibited by a group of synthetic compounds that apparently act by binding to a plasma membrane protein known as the naphthylphthalamic acid (NPA) receptor. No endogenous ligand to the NPA receptor, capable of affecting polar auxin transport in plants, has yet been found. It is now shown that a group of flavonoids including quercetin, apigenin, and kaempferol-can specifically compete with [(3)H]NPA for binding to its receptor and can perturb auxin transport in a variety of plant tissues and transport systems in a manner closely paralleling the action of synthetic transport inhibitors. Because the active flavonoids are widely distributed in the plant kingdom and exert their effects at micromolar concentrations approximating likely endogenous levels, they may act as natural auxin transport regulators in plants. PMID- 17734867 TI - Nuclear safeguards: the international atomic energy agency and world nuclear order. PMID- 17734866 TI - Darwin's Early Thoughts: Charles Darwin's Notebooks, 1836-1844. PMID- 17734865 TI - Acoustical Detection of High-Density Krill Demersal Layers in the Submarine Canyons off Georges Bank. AB - High-density demersal layers of krill have been detected in the submarine canyons off Georges Bank by means of a high-frequency, dual-beam bioacoustical technique. Krill densities in these demersal layers were observed to be two to three orders of magnitude greater than the highest densities observed in water-column scattering layers. Such abundances may help explain the unusually high squid and demersal fish production estimates attributed to the Georges Bank ecosystem. PMID- 17734868 TI - The work of spemann: the heritage of experimental embryology. PMID- 17734869 TI - Volcanic rocks: mantle xenoliths. PMID- 17734870 TI - Products & materials. PMID- 17734871 TI - SEA-SICKNESS. PMID- 17734872 TI - COMMENT AND CRITICISM. PMID- 17734873 TI - THE MEETING OF THE ECONOMIC AND HISTORICAL ASSOCIATIONS. PMID- 17734874 TI - NEW ZEALAND LETTER. PMID- 17734876 TI - EXPLORATION AND TRAVEL. PMID- 17734875 TI - HEALTH MATTERS. PMID- 17734877 TI - The occurrence of similar inventions in areas widely apart. PMID- 17734879 TI - The causation of consumption. PMID- 17734878 TI - The equivalence in time of American marine and intracontinental tertiaries. PMID- 17734880 TI - An American dialect society. PMID- 17734881 TI - A cretaceous river-bed. PMID- 17734882 TI - The pelvis of the dugong. PMID- 17734883 TI - Electrical phenomena at the Washington monument. PMID- 17734885 TI - The maxillo-palatines of Tachycineta. PMID- 17734884 TI - No parietal foramen in Tritylodon. PMID- 17734886 TI - Railway jubilee, Paris, 1887. PMID- 17734888 TI - COMMENT AND CRITICISM. PMID- 17734887 TI - SETTLEMENT OF LABOR DIFFERENCES. PMID- 17734890 TI - FOOD-CONSUMPTION. PMID- 17734889 TI - APPARITIONS AND HAUNTED HOUSES. PMID- 17734892 TI - THE PROPOSED FISHERIES BOARD OF GREAT BRITAIN. PMID- 17734891 TI - ELECTRIC LIGHTING IN ENGLAND. PMID- 17734893 TI - EXPLOSIONS IN COAL-MINES. PMID- 17734894 TI - Names of the Canadian Rocky Mountain peaks. PMID- 17734895 TI - Preliminary description of a new squirrel from Minnesota (Sciurus carolinensis hypophaeus sp. nov.). PMID- 17734896 TI - A convenient way of indicating localities upon labels. PMID- 17734897 TI - Science at Cornell. PMID- 17734898 TI - The endocrine system. PMID- 17734899 TI - The endocrine system. PMID- 17734900 TI - Geostationary satellites. PMID- 17734901 TI - Solar photovoltaic power systems: an electric utility R & d perspective. AB - Solar photovoltaic technology is receiving increasing attention as a prospective source of bulk, electric utility power within the next 10 to 20 years. Successful development will require solar energy conversion efficiencies of about 15 percent for photovoltaic flat-plate modules, or about 25 percent for photovoltaic cells using highly concentrated sunlight. Three different cell technologies have a better than even chance of achieving these target efficiencies with costs and operating lifetimes that would allow significant use by electric utilities. The challenge for the next decade is to push photovoltaic technology to its physical limits while expanding markets and user confidence with currently available systems. PMID- 17734902 TI - Conservation of rice genetic resources: luxury or necessity? PMID- 17734904 TI - Britain Studies Withdrawal from CERN. PMID- 17734903 TI - Reagan Offers a Chemical Weapons Treaty: But he declines to resume bilateral talks, which might speed agreement. AB - There is remarkably rich diversity in the cultivated rices and their wild relatives. Substantial segments of the diverse germplasm have been collected and conserved during the past two decades by national, regional, and international research centers. Multidisciplinary and interinstitutional evaluation and use have drawn substantial rewards. However, nations in the developing world that grow and consume rice still face enormous challenges to meet the continuous growth of the human population. Further conservation efforts and improved preservation measures are needed to provide security for the irreplaceable rice germplasm. Modest inputs into conservation programs are highly justified by multibillion dollar returns from the improved varieties in the past two decades. PMID- 17734905 TI - The Procrastinator's Power Source: The fuel cell beckons in the 1990's not just with cleanness and efficiency but as a way to put off coal and nuclear investments. PMID- 17734906 TI - The fuel cell: h2 + o2 + 150 years. PMID- 17734907 TI - Second lunar meteorite identified. PMID- 17734908 TI - Landslides from Volcaooes Seen as Common: Given the example of Mount St. Helens' catastrophic collapse, geologists are recognizing volcanic debris avalanches elsewhere. PMID- 17734909 TI - Wallace and darwinism: just before the origin. PMID- 17734910 TI - Radiation theory between 1896 and 1925: the tiger and the shark. PMID- 17734912 TI - Marine communities: biotic interactions in recent and fossil benthic communities. PMID- 17734911 TI - Avian population biology: the arctic skua. PMID- 17734913 TI - Cenozoic high latitude heterochroneity of southern hemisphere marine faunas. AB - Discovery of 11 genera, in five classes within the Mollusca, Echinodermata, and Arthropoda in upper Eocene rocks on Seymour Island, Antarctica, previously known only from Late Cenozoic in mid-latitudes, suggests that the high latitude region of the Southern Hemisphere acted as a center of origin and dispersal for a broad spectrum of taxa. Precursors to modern deep- and shallow-water mid-latitude forms evolved and flourished in the high latitudes until conditions in lower latitudes favored their dispersal. These observations of Antarctic marine invertebrates corroborate those recently made about terrestrial mammals and plants in the Arctic. PMID- 17734914 TI - Catastrophic storms, el nino, and patch stability in a southern california kelp community. AB - Strong winter storms in southern California destroyed most of the canopy ofthe giant kelp Macrocystis pyrifera but not the patches of understory kelps in the Point Loma kelp forest near San Diego. Subsequent massive recruitment of Macrocystis juveniles and adults that survived the storms had low survival in the summer during the California El Nino of 1983. The combined disturbance may have long-lasting structural consequences for this community because, once established, the understory patches can resist invasion by Macrocystis. PMID- 17734915 TI - Ancient ice islands in salt lakes of the central andes. AB - Massive blocks of freshwater ice and frozen sediments protrude from shallow, saline lakes in the Andes of southwestern Bolivia and northeastern Chile. These ice islands range up to 1.5 kilometers long, stand up to 7 meters above the water surface, and may extend out tens of meters and more beneath the unfrozen lake sediments. The upper surfaces of the islands are covered with dry white sediments, mostly aragonite or calcite. The ice blocks may have formed by freezing of the fresh pore water of lake sediments during the "little ice age." The largest blocks are melting rapidly because of possibly recent increases in geothermal heat flux through the lake bottom and undercutting by warm saline lake water during the summer. PMID- 17734916 TI - Drosophila males contribute to oogenesis in a multiple mating species. AB - Two species of Drosophila that differ in their ecology and mating systems have been compared with respect to male contribution to the somatic tissues and developing oocytes of females. In the species Drosophila mojavensis females remate daily, exhibit a copulatory plug, and have been shown to obtain a contribution from the male ejaculate. In contrast, Drosophila melanogaster males do not contribute to females. Female Drosophila melanogaster do not remate as frequently as Drosophila mojavensis females nor is a copulatory plug formed. PMID- 17734918 TI - Multiple microtektite horizons in upper eocene marine sediments? PMID- 17734917 TI - Multiple microtektite horizons in upper eocene marine sediments? PMID- 17734919 TI - THE PHYSIOLOGY OF THE AVIATOR. PMID- 17734920 TI - A NEW DEPOSIT OF URANIUM ORE. PMID- 17734921 TI - APROPOS OF THE PROPOSED HISTORICAL SCIENCE SECTION. PMID- 17734922 TI - VITAMIN TESTS WITH CHICKS. PMID- 17734923 TI - TO CUT OFF LARGE TUBES OF PYREX GLASS. PMID- 17734925 TI - For Adults Only. PMID- 17734924 TI - THE ILLINOIS STATE ACADEMY OF SCIENCE. PMID- 17734926 TI - Pooling What with Whom? PMID- 17734927 TI - Science and the Citizen. PMID- 17734928 TI - National Academy of Sciences: Abstracts of Papers Presented at the Autumn Meeting, 18-20 November 1957, Rockefeller Institute and New York Botanical Garden, New York. PMID- 17734929 TI - News of Science. PMID- 17734930 TI - Respiration in Ulothrix zonata. PMID- 17734931 TI - Basic Chromosome Number of Four in the Subfamily Panicoideae of the Gramineae. PMID- 17734932 TI - Meetings and Societies. PMID- 17734934 TI - Of bergy bits and growlers. PMID- 17734933 TI - EQUIPMENT NEWS. PMID- 17734936 TI - Energy analysis. PMID- 17734937 TI - Energy analysis. PMID- 17734935 TI - Ph.d. Projections. PMID- 17734938 TI - Energy analysis. PMID- 17734939 TI - Response. PMID- 17734940 TI - Energy analysis. PMID- 17734941 TI - A century of chemical progress. PMID- 17734942 TI - Transportation energy conservation policies. PMID- 17734943 TI - NIH: Cancer Institute Politics Complicate a Difficult Case. PMID- 17734944 TI - NCI Director Set to Leave. PMID- 17734945 TI - National forests: court ruling spurs clear-cutting controversy. PMID- 17734946 TI - Science in the European community: deadlock on fusion. PMID- 17734947 TI - Biological warfare: suspicions of soviet activity. PMID- 17734948 TI - Solar research institute starts out in partial eclipse. PMID- 17734949 TI - Brain biochemistry: effects of diet. PMID- 17734950 TI - June colloquium on R & d in the federal budget. PMID- 17734951 TI - AAAS Conference on Science and Social Problems. PMID- 17734952 TI - Science education and educational policies. PMID- 17734953 TI - Atlanta Area AAAS Group to Meet. PMID- 17734954 TI - AAAS Affiliate Works to Promote Equal Opportunity for Women. PMID- 17734955 TI - Second Half of Current NOVA Season Announced. PMID- 17734956 TI - The Indian science congress, 1976--an agenda for action. PMID- 17734957 TI - Chemistry of the sea. PMID- 17734958 TI - Fluviology. PMID- 17734959 TI - Lipids in plants. PMID- 17734960 TI - Space physics. PMID- 17734961 TI - Solar Absorption in a Stratosphere Perturbed by NOx Injection. AB - The changes in the solar absorption by nitrogen dioxide and ozone induced by the injection of NO(x) (oxides of nitrogen) in the stratosphere are complementary, even though the nitrogen dioxide absorption is only a small fraction of the ozone absorption for an unperturbed stratosphere. The factors causing this effect are described, and an analysis is made of the perturbed solar radiation budget. PMID- 17734962 TI - Palaeosclerotium, a pennsylvanian age fungus combining features of modern ascomycetes and basidiomycetes. AB - Fruiting bodies described previously as sclerotia of Palaeosclerotium pusillum are cleistothecium-like, enclosed structures, containing spores within an ascus. The cleistothecia are composed of hyphae having dolipore-like septa and are attached to vegetative hyphae having clamp connections. The unique combination of ascomycete-like reproductive bodies and basidiomycete-like hyphae present in this Pennsylvanian fungus suggests that there already existed, during the Middle Pennsylvanian period, a group of fungi intermediate between the Ascomycetes and Basidiomycetes. PMID- 17734963 TI - Tool use in a social insect and its implications for competitive interactions. AB - Four species of myrmicine ants, Aphaenogaster rudis, A. treatae, A. tennesseensis, and A. fulva, use pieces of leaf, mud, and sand grains as tools to carry soft foods from distant sources to the colony. Tools are tended on the food and removed by colony members without regard to which individual brought the tool. Food is gathered more efficiently by tool use than by internal transport. Tool-using behavior may increase the competitive ability of A. rudis in an interspecific dominance hierarchy. PMID- 17734964 TI - Oroville earthquakes: normal faulting in the sierra nevada foothills. AB - Aftershocks of the Oroville, California, earthquake of 1 August 1975 define a 16- by 12-kilometer fault plane striking north-south and dipping 60 degrees to the west to a depth of 10 kilometers. Focal mechanisms from P-wave first motions indicate normal faulting with the western, Great Valley side downdropped relative to the Sierra Nevada block. The northward projection of the fault plane passes beneath Oroville Dam and crops out under the reservoir. PMID- 17734965 TI - SOME MODERN CONCEPTIONS OF AMEBIASIS. PMID- 17734966 TI - ANTON JULIUS CARLSON. PMID- 17734968 TI - SURVEY OF THE AMERICAN FORESTRY ASSOCIATION. PMID- 17734967 TI - EPHRAIM PORTER FELT 1868-1943. PMID- 17734969 TI - GRANTS-IN-AID OF THE PERMANENT SCIENCE FUND OF THE AMERICAN ACADEMY OF ARTS AND SCIENCES. PMID- 17734970 TI - LECTURES ON MEDICAL EDUCATION. PMID- 17734971 TI - THE TORREY BOTANICAL CLUB. PMID- 17734973 TI - VITAMER OR ISOTEL? BOTH? PMID- 17734972 TI - THE COMMONWEALTH FUND AND MEDICAL RESEARCH. PMID- 17734974 TI - CENTRALIZATION OF PERSONAL RECORDS. PMID- 17734975 TI - CLARASE INACTIVATION OF PENICILLIN. PMID- 17734976 TI - EDITORIAL CHANGES IN SCIENTIFIC PAPERS. PMID- 17734977 TI - ABSENCE OF AUDIOGENIC SEIZURES IN WILD NORWAY AND ALEXANDRINE RATS. PMID- 17734978 TI - CHANGES IN ACID-SOLUBLE PHOSPHORUS COMPOUNDS IN THE BRAIN IN POLIOMYELITIS. PMID- 17734979 TI - A METHOD OF OPENING LYOPHILE TUBES. PMID- 17734980 TI - SCIENCE NEWS. PMID- 17734981 TI - PREVENTION OF DISEASE. PMID- 17734982 TI - ORGANIZED COOPERATION AMONG MUSEUMS. PMID- 17734983 TI - THE FRANKLIN INSTITUTE. PMID- 17734984 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17734985 TI - EDWARD HITCHCOCK AND THE ORIGIN OF THE ASSOCIATION OF AMERICAN GEOLOGISTS. PMID- 17734986 TI - SCIENCE AND INDUSTRY. PMID- 17734987 TI - BALL LIGHTNING. PMID- 17734988 TI - SENSITIVE FLAMES AND APPARENT FLAME PRESSURE. PMID- 17734989 TI - SECTION V--BIOLOGICAL SCIENCES. PMID- 17734990 TI - This week in science. PMID- 17734991 TI - Evolving state-university-industry relations. PMID- 17734992 TI - Erratum. AB - In the review of Polycyclic Hydrocarbons and Carcinogensis (6 Dec., p. 1155), the fourth sentence of the third paragraph should have read: "A higher proportion of anti BPDE is produced in peroxide-dependent oxidation than in cytochrome P-450 dependent epoxidation, for example." PMID- 17734993 TI - Complexity. PMID- 17734994 TI - Archeology congress. PMID- 17734995 TI - Archeology congress. PMID- 17734996 TI - Fiscal Neglect Breeds Problems for Seed Banks: A lawsuit and a stack of reports suggest that the national system for preserving seeds for plant breeding is in trouble. PMID- 17734997 TI - Limited ASAT Proposal Gains Backers: Pressured by a congressional ban on ASAT tests, some Administration officials express interest in a limited arms agreement, but the Air Force remains uninterested. PMID- 17734998 TI - Fossil research faces sharp cutbacks in '87. PMID- 17734999 TI - Nuclear testing up sharply under reagan. PMID- 17735000 TI - Acid rain plan draws mixed review. PMID- 17735001 TI - Rancho seco reactor suffers another mishap. PMID- 17735002 TI - Shakespeare's New Poem: An Ode to Statistics: Two statisticians are using a powerful method to determine whether Shakespeare could have written the newly discovered poem that has been attributed to him. PMID- 17735003 TI - Is Cygnus X-3 a Quark Star?: From a distance of 37,000 light years, the most luminous x-ray source in the galaxy seems to be showering the earth with a new kind of particle; could it be quark matter? PMID- 17735004 TI - The Sun Is Fading: The decrease in solar brightness is small but possibly climatically significant; a turnaround may be in the offing. PMID- 17735005 TI - Bell labs transistor sets a speed record. PMID- 17735006 TI - Cell lineages traced in zebrafish embryos. PMID- 17735007 TI - The origin of the moon. AB - The origin of the moon is considered within the theory of formation of the terrestrial planets by accumulation of planetesimals. The theory predicts the occurrence of giant impacts, suggesting that the moon formed after a roughly Mars sized body impacted on the protoearth. The impact blasted portions of the protoearth and the impacting body into geocentric orbit, forming a prelunar disk from which the moon later accreted. Although other mechanisms for formation of the moon appear to be dynamically impossible or implausible, fundamental questions must be answered before a giant impact origin can be considered both possible and probable. PMID- 17735008 TI - Electrons in silicon microstructures. AB - Silicon microstructures only a few hundred atoms wide can be fabricated and used to study electron transport in narrow channels. Spatially localized voltage probes as close together as 0.1 micrometer can be used to investigate a variety of physical phenomena, including velocity saturation due to phonon emission, the local potentials caused by scattering from a single trapped electron, and quantum tunneling or hopping among very few electron states. PMID- 17735009 TI - Optical activity and ferroelectricity in liquid crystals. AB - Some liquid-crystalline phases of optically active materials are themselves optically active and have dissymmetric structures. The cholesteric phase and smectics C,I, and F have a helical order of their molecules. Plane-polarized light is rotated by the helix, and when the pitch of the helix is comparable to the wavelength of visible light, these phases will reflect irridescent light of a single color. The smectics phases can exhibit ferroelectricity and have been utilized recently in fast-switching light valves. A relation between the microscopic property of molecular configuration and the macroscopic properties of ferroelectricity and the rotation of plane-polarized light is developed. PMID- 17735010 TI - Selenium in organic synthesis. AB - The introduction, manipulation, and ultimate removal of selenium-containing functional groups allow a variety of synthetically useful processes to be accomplished in high overall yields under mild conditions. In particular, transformations such as allylic oxidations, nucleophile-induced cleavage reactions, regiospecific alkylations, and olefin cofunctionalizations can be readily achieved by taking advantage of selenium's unique properties. PMID- 17735011 TI - The 1985 nobel prize in chemistry. PMID- 17735012 TI - Tissue-specific cell lineages originate in the gastrula of the zebrafish. AB - In the zebrafish, cells of a clone derived from a single blastomere migrate away from one another during gastrulation. Later in development their descendants are usually found scattered within several different types of tissues of embryo. The divisions and migrations of individual cells were monitored during early development, revealing that in most cases the lineal descendants of single cells present at gastrula stage exclusively populate only single tissues, and may have stereotyped positional relationships within these tissues. Thus the gastrula stage is the first stage when heritable restrictions in cell type might arise in the zebrafish. PMID- 17735013 TI - Ingestion of petroleum by seabirds can serve as a monitor of water quality. AB - The ingestion by seabirds of fossil fuel hydrocarbons and other pollutants has been of great interest. This paper reports that storm-petrels ingest petroleum at sea and that residues can be detected in their stomach oil. The incidence of gut samples containing fossil fuel hydrocarbons (dirty samples) increased significantly after oil spills, and significantly more birds regurgitated dirty samples after large nearby spills than small distant ones. This appears to be one of the first reported instances where individuals of a natural population of marine birds have been shown to ingest sublethal doses of oil from sources of low level, long-term pollution or from oil spills. Because of certain natural traits, Procellariiformes could serve as monitors of pollutants in the marine environment. PMID- 17735014 TI - Sevenless: a cell-specific homeotic mutation of the Drosophila eye. AB - Each ommatidium in the compound eye of the Drosophila mutant sevenless lacks photoreceptor number seven (R7) from the normal ommatidial complement of eight photoreceptors. A comparison of mutant and normal development reveals that this deficit is caused by the cell-specific transformation of the cell normally fated to produce R7 into a lens-secreting accessory cell, a cone cell. PMID- 17735016 TI - Roots of criminality: crime and human nature. PMID- 17735015 TI - R&D and the Budget Crisis: Eleventh Annual AAAS Colloquium on R&D Policy. PMID- 17735017 TI - German science abroad: cultural imperialism and exact sciences. PMID- 17735019 TI - Algal fossils: paleoalgology. PMID- 17735018 TI - Cell proliferation: the biology of cell reproduction. PMID- 17735020 TI - Products & materials. PMID- 17735021 TI - COMMENT AND CRITICISM. PMID- 17735022 TI - THE FALL MEETING OF THE NATIONAL ACADEMY. PMID- 17735023 TI - THE HARVARD CELEBRATION. PMID- 17735024 TI - The teaching of natural history. PMID- 17735025 TI - Butter and fats. PMID- 17735026 TI - Coloring geological maps. PMID- 17735027 TI - Anemometer exposure. PMID- 17735028 TI - Lunar studies. PMID- 17735029 TI - Soviet anti-semitism: reply by pontryagin. PMID- 17735030 TI - Interferon. PMID- 17735031 TI - Education for the 21st century. PMID- 17735032 TI - The colorado plateaus: cultural dynamics and paleoenvironment. AB - Convergent archeological, geological, palynological, dendrochronological, and radiometric data provide a paleoenvironmental record for the American Southwest at a level of detail and time resolution not previously achieved. Many prehistoric cultural and demographic changes on the Colorado Plateaus coincided with environmental fluctuations defined by precisely dated geoclimatic and bioclimatic indicators. These coincidences support the interpretation that socioeconomic changes and population displacements were commonly triggered by environmental stress. PMID- 17735034 TI - Agricultural network fights unwelcome gift. PMID- 17735033 TI - Economic benefits from research: an example from agriculture. AB - In this article we examine the economic benefits of the long history of public research in agriculture. Agricultural productivity continues to grow. Annual rates of return on research expenditure are of the order of 50 percent. Research oriented to science is profitable when associated with technological research. Decentralization, as in the system of state agricultural experiment stations and substations, has allowed close association of research oriented to science with that oriented to technology and to farming. The high rate of return shows that investment in public research in agriculture is too low. This is at least partially because research benefits spill over to other regions and to consumers, reducing the incentives for local support. PMID- 17735035 TI - "Truth-in-Testing" Attracts Diverse Support. PMID- 17735036 TI - Surgeon general says get healthy, eat less meat. PMID- 17735037 TI - Scientific american to be published in china. PMID- 17735039 TI - Pop nutrition books face legal hurdles. PMID- 17735038 TI - Dollar-a-Gallon Gas Fuels Metric Conversion. PMID- 17735040 TI - Test coaching dispute lingers. PMID- 17735041 TI - How is new ocean crust formed? PMID- 17735042 TI - Molecular biologists and their world. PMID- 17735043 TI - SALT: Questions and Interpretations. PMID- 17735044 TI - Hunter-gatherers today. PMID- 17735045 TI - Littoral philosophy. PMID- 17735046 TI - Mathematical physics. PMID- 17735047 TI - Nitrous oxide emissions from an irrigated cornfield. AB - During the 1978 growing season, nitrous oxide (N(2)O) emissions from a typical well-managed northern Colorado field of corn (Zea mays L.) totaled approximately 2.6 kilograms of nitrogen per hectare, or about 1.3 percent of the applied fertilizer nitrogen. Thirty percent of the loss occurred during the 3 weeks following fertilization while ammonia was being rapidly nitrified, and 59 percent was emitted during the week after the field's first irrigation, when restricted oxygen diffusion favored denitrification. Considering the large spatial and temporal variability of N(2)O emissions from soil, micrometeorological estimates of vertical N(2)O flux density compared favorably with estimates based on a simple soil cover method. PMID- 17735048 TI - Carbon-13 in tree rings indicates no record of sea-surface temperature. AB - When the correct values for the temperature coefficient of carbon dioxide solubility in seawater are used, theoretical calculations show that no measurable carbon-isotope redistribution occurs between sea and air for any plausible change in the sea-surface temperature. Although this fact invalidates one possible paleothermometer, it somewhat simplifies the interpretation of carbon-13 data in terrestrial biological samples. PMID- 17735049 TI - Giant larvacean houses: observations from deep submersibles. AB - The abundance of large, previously unknown larvacean feeding structures in the deep ocean is a striking contrast to the rarity of such forms taken in net hauls. In some areas, abandoned houses and their disintegrated parts provide a substrate for other organisms and contribute to organic aggregates. PMID- 17735050 TI - The viscous sublayer at the sea floor. AB - A 0.6-centimeter-thick sublayer was found in horizontal flow profiles obtained by traversing a heated thermistor from 19 centimeters above to 2 centimeters below the water-sediment interface in 200-meter-deep water on the Oregon continental shelf. In this sublayer the speed of the current varies linearly with distance above the sediment. Estimates of viscous stress from this sublayer and turbulent stress from the profile agree within 5 percent. Stress calculated from a current meter spectrum agrees within its 95 percent confidence limits. PMID- 17735051 TI - Gravitational Lens of the Sun: Its Potential for Observations and Communications over Interstellar Distances. AB - The gravitational field of the sun acts as a spherical lens to magnify the intensity of radiation from a distant source along a semi-infinite focal line. A spacecraft anywhere on that line in principle could observe, eavesdrop, and communicate over interstellar distances, using equipment comparable in size and power with what is now used for interplanetary distances. If one neglects coronal effects, the maximum magnification factor for coherent radiation is inversely proportional to the wavelength, being 100 million at 1 millimeter. The principal difficulties are that the nearest point on the focal half-line is about 550 times the sun-earth distance, separate spacecraft would be needed to work with each stellar system of interest, and the solar corona would severely limit the intensity of coherent radiation while also restricting operations to relatively short wavelengths. PMID- 17735052 TI - Determination of the pore size of cell walls of living plant cells. AB - The limiting diameter of pores in the walls of living plant cells through which molecules can freely pass has been determined by a solute exclusion technique to be 35 to 38 angstroms for hair cells of Raphanus sativus roots and fibers of Gossypium hirsutum, 38 to 40 angstroms for cultured cells of Acer pseudoplatanus, and 45 to 52 angstroms for isolated palisade parenchyma cells of the leaves of Xanthium strumarium and Commelina communis. These results indicate that molecules with diameters larger than these pores would be restricted in their ability to penetrate such a cell wall, and that such a wall may represent a more significant barrier to cellular communication than has been previously assumed. PMID- 17735053 TI - Vibrations: their signal function for a spider kleptoparasite. AB - The stealing behavior of Argyrodes elevatus suggests that this kleptoparasitic spider monitors the movements and the hunting success of its web-building host. Wrapping of prey by the host regularly elicits raids from the kleptoparasite. The prey-catching activities of the host generate vibrations that were recorded with a position-sensing photodiode. The recordings indicated that wrapping movements produce a characteristic pattern of vibrations. PMID- 17735054 TI - The cheetah: native american. AB - Two North American fossil species of large felids, hitherto regarded as Late Cenozoic pumas (mountain lion), are in fact closely related to the living cheetah, Acinonyx, of Africa and Eurasia. A new subgenus (Miracinonyx) is proposed for the American species. Cheetahs and pumas may have had a common ancestor in the Miocene of North America. PMID- 17735055 TI - High-speed cinematographic evidence for ultrafast feeding in antennariid anglerfishes. AB - Analyses by means of high-speed, light cinematography at 800 and 1000 frames per second have shown that members of the shallow-water anglerfish genus Antennarius are capable of producing an enormous suction pressure for prey capture by means of an extraordinarily rapid expansion of the buccal and opercular cavities. Prey is totally engulfed at speeds considerably greater than those recorded for any other fish. The structural adaptations responsible for this rapid prey engulfment provide anglerfishes with one of the fastest known vertebrate feeding mechanisms. PMID- 17735056 TI - PRODUCTS and MATERIALS. PMID- 17735057 TI - SCIENCE NEWS. PMID- 17735058 TI - STATISTICAL INFERENCE. PMID- 17735059 TI - ROGER WEBB GANNETT. PMID- 17735060 TI - BIOLOGICAL RESEARCH AT THE SCRIPPS INSTITUTION OF OCEANOGRAPHY. PMID- 17735062 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17735061 TI - BLACK CHAFF OF WHEAT IN RUSSIA. PMID- 17735063 TI - THE TREATMENT OF WART DISEASE OF POTATOES WITH SULPHUR. PMID- 17735065 TI - THE ATTITUDE OF THE ELECTRICAL RAILWAY COMPANIES ON ELECTROLYSIS. PMID- 17735066 TI - THE IONS OF INERT GASES AS CATALYSTS. PMID- 17735064 TI - A SEISMOLOGICAL NOTE. PMID- 17735067 TI - THE NEW STATUS OF NET ENERGY DETERMINATION. PMID- 17735068 TI - SOME ECOLOGICAL RELATIONS OF THE HYPOGAEOUS FUNGI. PMID- 17735069 TI - RESEARCH IN EUGENICS. PMID- 17735070 TI - JOEL ASAPH ALLEN. PMID- 17735072 TI - THE USE OF VITAMINE FOOD-TABLETS AS AN AID TOWARD CONSERVING THE FOOD SUPPLY. PMID- 17735071 TI - A BIRD'S-EYE VIEW OF AMERICAN LANGUAGES NORTH OF MEXICO. PMID- 17735073 TI - A SIMPLE APPARATUS FOR MICRO-MANIPULATION UNDER THE HIGHEST MAGNIFICATIONS OF THE MICROSCOPE. PMID- 17735075 TI - ASTRONOMICAL MEETING AT THE POTSDAM ASTRONOMICAL OBSERVATORY. PMID- 17735074 TI - CHROMOSOME RELATIONSHIPS IN WHEAT. PMID- 17735076 TI - AMERICAN MATHEMATICAL SOCIETY. PMID- 17735077 TI - COMMENT AND CRITICISM. PMID- 17735078 TI - THE PRESENT CONDITION OF THE COAST SURVEY. PMID- 17735079 TI - SORGHUM SUGAR. PMID- 17735080 TI - LONDON LETTER. PMID- 17735081 TI - Polydactylism. PMID- 17735082 TI - Larval amblystomas for laboratory work. PMID- 17735083 TI - How astronomers may work. PMID- 17735085 TI - Earthquake sounds. PMID- 17735084 TI - Psychology of the bear. PMID- 17735086 TI - Alligators in the Bahamas. PMID- 17735088 TI - The significance of coincident weather-conditions. PMID- 17735087 TI - Millerite. PMID- 17735089 TI - Visual illusion. PMID- 17735090 TI - A large squid. PMID- 17735091 TI - Barometer exposure. PMID- 17735092 TI - BIOLOGICAL NOTES FROM NEW ZEALAND. PMID- 17735093 TI - BRILLIANT AURORAe OF 1892. PMID- 17735094 TI - THE PSYCHOLOGICAL LABORATORY AT YALE. PMID- 17735095 TI - HYBRIDISM EXEMPLIFIED IN THE GENUS COLAPTES. PMID- 17735096 TI - CONCERNING OUR WASTE GROUND. PMID- 17735097 TI - BOTANY AT THE EXPERIMENT STATIONS. PMID- 17735098 TI - THE GREEN MOUNTAINS' ANTICLINAL. PMID- 17735099 TI - THE RETICULATED STRUCTURE OF HUMAN RED BLOOD-CORPUSCLES. PMID- 17735100 TI - The Cretaceous at Gay Head, Martha's Vineyard. PMID- 17735101 TI - The Humming-Bird's Food. PMID- 17735102 TI - Remains of the Mastodon Recently Found in Tennessee. PMID- 17735103 TI - Meteoric Shower. PMID- 17735104 TI - On the Vernacular Name of the Genus Harporhynchus. PMID- 17735105 TI - THE RESULT OF THE LAST TWENTY YEARS OF AGRICULTURAL RESEARCH. PMID- 17735106 TI - THE ROYAL GEOGRAPHICAL SOCIETY. PMID- 17735108 TI - DOCTORATES CONFERRED BY AMERICAN UNIVERSITIES. PMID- 17735107 TI - AIR IN THE DEPTHS OF THE OCEAN. PMID- 17735109 TI - AN ANOMALOUS EFFECT OF RONTGEN RAYS. PMID- 17735110 TI - THE ACID SPOTTING OF MORNING GLORIES BY CITY RAIN. PMID- 17735111 TI - TRANSFORMATION OF GRAVITATIONAL WAVES INTO ETHER VORTICES. PMID- 17735112 TI - THE SPECIFIC GRAVITY OF SILT. PMID- 17735114 TI - INAUGURAL ADDRESS OF THE PRESIDENT OF THE STEVENS INSTITUTE OF TECHNOLOGY. PMID- 17735115 TI - THE SOCIETY OF AMERICAN BACTERIOLOGISTS. PMID- 17735113 TI - ON PSYCHOLOGY AND MEDICAL EDUCATION. PMID- 17735116 TI - THE PUBLICATION OF REJECTED NAMES. PMID- 17735118 TI - WILL-MAKING. PMID- 17735117 TI - MOTION OF TRANSLATION OF A GAS IN A VACUUM. PMID- 17735119 TI - SLEEPY GRASS AND ITS EFFECT ON HORSES. PMID- 17735120 TI - THE VERTEBRAL COLUMN OF BRONTOSAURUS. PMID- 17735122 TI - THE ROCKEFELLER INSTITUTE FOR MEDICAL RESEARCH. PMID- 17735121 TI - AMERICAN MUSEUM OF NATURAL HISTORY. PMID- 17735123 TI - SCIENCE NEWS. PMID- 17735125 TI - THE CONTRIBUTION OF BIOLOGY, CHEMISTRY AND PHYSICS TO THE NEWER KNOWLEDGE OF RICKETS. PMID- 17735124 TI - SOME APPLICATIONS OF PALEONTOLOGY. PMID- 17735127 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17735126 TI - ACOUSTICS OF AUDITORIUMS. PMID- 17735128 TI - SCIENCE AND SECRETARIES. PMID- 17735129 TI - RE SPECIATION WITHOUT CLIMATIC CHANGE OR GEOGRAPHIC ISOLATION. PMID- 17735130 TI - LEPIDOPTERA OF NEW YORK. PMID- 17735131 TI - WEIGHT AND HUMIDITY. PMID- 17735134 TI - A UNIVERSAL MUSCLE LEVER. PMID- 17735132 TI - THE BRASSO FOSSILIFEROUS MIOCENE OF TRINIDAD, WEST INDIES. PMID- 17735133 TI - THE EASTLAND HORNED "TOAD". PMID- 17735135 TI - METHOD FOR GROWING SMALL-SEEDED PLANTS UNDER STERILE CONDITIONS. PMID- 17735136 TI - THE OVERWINTERING IN MASSACHUSETTS OF IXODIPHAGUS CAUCURTEI. PMID- 17735137 TI - AN EFFICIENCY FORMULA FOR DAIRY COWS. PMID- 17735138 TI - THE AGE OF SCIENCE. PMID- 17735139 TI - HIGHER EDUCATION IN GERMANY AND THE UNITED STATES. PMID- 17735140 TI - Catalogue of the Ward-Coonley Collection of Meteorites. By HENRY A. WARD, A.M., LL.D. Pp. xii + 113, with 10 plates. Published by the Author. Chicago, May, 1904. PMID- 17735141 TI - Le Mouvement. By R. S. WOODWORTH. Paris, O. Doin. 1903. Pp. viii+421. 4 fr. PMID- 17735142 TI - KINDERGARTEN SCIENCE. PMID- 17735143 TI - A NOTABLE PALEOBOTANICAL DISCOVERY. PMID- 17735144 TI - 'VEGETABLE BALLS.'. PMID- 17735146 TI - AGRICULTURAL EXHIBITS AT ST. LOUIS. PMID- 17735145 TI - EVOLUTION AND PHYSICS. PMID- 17735148 TI - THE ADDRESS OF THE PRESIDENT OF THE ROYAL MICROSCOPICAL SOCIETY. PMID- 17735147 TI - HONORARY DEGREES CONFERRED BY THE UNIVERSITY OF WISCONSIN. PMID- 17735149 TI - THE NEW COMET. PMID- 17735150 TI - THE BLUE COLOR OF THE SKY. PMID- 17735151 TI - LETTERS TO THE EDITOR. PMID- 17735152 TI - COMET OBSERVATIONS AT PRINCETON. PMID- 17735153 TI - DOLBEAR'S NEW TELEPHONE SYSTEM. PMID- 17735154 TI - UPON A MODIFICATION OF WHEATSTONE'S MICROPHONE, AND ITS ADAPTABILITY TO RADIOPHONIC RESEARCHES. PMID- 17735156 TI - ALCOHOL IN WATER AND AIR. PMID- 17735155 TI - ASTRONOMY. PMID- 17735158 TI - THE TELEPHONIC RECEIVER. PMID- 17735157 TI - ALTERATION OF MILK. PMID- 17735159 TI - SCIENCE NEWS. PMID- 17735160 TI - WINGS FOR THE SPIRIT. PMID- 17735161 TI - COMMEMORATION OF THE BI-CENTENARY OF THE DEATH OF NEWTON. PMID- 17735163 TI - TREE FROGS AND PITCHER PLANTS. PMID- 17735162 TI - FRANK W. VERY. PMID- 17735164 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17735166 TI - COLORIMETRIC METHODS IN BIOLOGY. PMID- 17735165 TI - THE OCCURRENCE OF CONJUGATION IN PARAMECIUM CALKINSI. PMID- 17735167 TI - CENTRIFUGING FILTERABLE VIRUSES. PMID- 17735169 TI - SPECIALIZATION AND COOPERATION IN SCIENTIFIC RESEARCH. PMID- 17735170 TI - CHILDREN WHO RUN ON ALL FOURS. PMID- 17735168 TI - A FUNCTION OF REGIONAL SCIENTIFIC SOCIETIES. PMID- 17735171 TI - MODIFIED WATER REGULATOR FOR SMALL TANKS. PMID- 17735172 TI - A PHOTOGRAPHIC PLATE THAT PENETRATES DESERT HAZE. PMID- 17735173 TI - SOME DEVONIAN PLANT LOCALITIES OF CENTRAL AND WESTERN NEW YORK. PMID- 17735174 TI - EFFECT OF ULTRA-VIOLET LIGHT UPON DIGITALIS PURPUREA. PMID- 17735175 TI - The cretaceous-tertiary transition. AB - The fossil sequences from cores across the Cretaceous-Tertiary boundary show a, range of transition times and transition time intervals depending on the fossil indicators and the location of the site. These variations, together with the pattern of iridium distribution with depth at some sites, differences in total amounts of iridium, variations in noble metal abundances normalized to extraterrestrial concentrations, the depositional effects that might be expected in a reducing environment, and the clay mineralogy of the boundary layer clays, put into question the interpretation that an extraterrestrial event was the cause of the faunal changes and the iridium anomaly in the vicinity of the Cretaceous Tertiary transition. It seems more likely that an explanation for the changes during the transition will come from continued examination of the great variety of terrestrial events that took place at that time, including extensive volcanism, major regression of the sea from the land, geochemical changes, and paleoclimatic and paleoceanographic changes. PMID- 17735176 TI - Science and technology in Mexico: toward self-determination. AB - During the last decade Mexico has moved progressively to develop and naturalize its scientific and technological capabilities, a decision requiring long-term government investment in education and research. The areas in which Mexico's National Council of Science and Technology selected to focus a national development program include the following: scholarships for middle- as well as high-level researchers and technicians; indicative programs to support research and basic or new industries in fields such as energy, electronics, metalworking, and agronomy; a government-industry shared risk program; research centers, many located in the provinces; and international scientific agreements. The translation of scientific classics and contemporary publications into Spanish and their widespread dissemination in Mexico have received special attention as has the dissemination of Mexico's work worldwide. PMID- 17735177 TI - EPA's Troubles Reach a Crescendo. PMID- 17735178 TI - Congress investigates malfeasance at EPA. PMID- 17735179 TI - President tells agencies to lower patent bars. PMID- 17735180 TI - Would uncle sam sell the farm? PMID- 17735181 TI - History of Science Group Wins NEH Challenge Grant. PMID- 17735182 TI - Science, math education legislation on track. PMID- 17735183 TI - Landsat plan hits stormy weather. PMID- 17735184 TI - Finches show competition in ecology. PMID- 17735185 TI - When is a metal not a metal? PMID- 17735187 TI - Fraud in science. PMID- 17735186 TI - Inflation and the arrow of time. PMID- 17735188 TI - Ecological interdependences. PMID- 17735190 TI - Salt appetite. PMID- 17735189 TI - Solar astronomy. PMID- 17735191 TI - Plant Cover and Biomass Response to Clear-Cutting, Site Preparation, and Planting in Pinus elliottii Flatwoods. AB - Pine plantation management did not initially convert natural forests to monocultures; rather it increased plant species richness and diversity. During a 5-year study of two natural watersheds in Florida that were converted to plantations, woody species diminished, but herbaceous species increased. Number of plant species on permanent transects and plots increased. Diversity of cover, frequency, and biomass did not diminish or else increased after harvest. PMID- 17735192 TI - Pleistocene sea levels from raised coral reefs of haiti. AB - The elevations and ages of a sequence of three uplifted Pleistocene coral reefs on the Northwest Peninsula of Haiti have been determined. With the assignment of a sea level of +6 meters (relative to the present day) at 130,000 years before present and constant uplift of the reefs, the data indicate that sea level stood 10 and -13 meters at 108,000 and 81,000 years before present, respectively. These results are in substantial agreement with those reported for Barbados and New Guinea and support the hypothesis of constant uplift for each area. Sea level data from raised reefs indicate that the interglacial marine oxygen isotope oscillations during oxygen isotope stage 5 are a result of 30 percent ice volume effects and 70 percent temperature effects. PMID- 17735193 TI - Residential firewood use in the United States. AB - An empirical relation between residential firewood use and population density was developed from survey data for 64 counties in New England and was corroborated by data from other states. The results indicate that usage is concentrated in urbanized areas of the Northeast and north central states and that about 9.0 to 11.0 percent of U.S. space heating input is from firewood. No constraints due to the supply of wood were apparent in 1978-1979. These findings have implications for effects on air quality. PMID- 17735194 TI - Quaternary pollen record from laguna de tagua tagua, chile. AB - Pollen of southern beech and podocarp at Laguna de Tagua Tagua during the late Pleistocene indicates that cooler and more humid intervals were a feature of Ice Age climate at this subtropical latitude in Chile. The influence of the southern westerlies may have been greater at this time, and the effect of the Pacific anticyclone was apparently weakened. The climate today, wet in winter and dry in summer, supports broad sclerophyll vegetation that developed during the Holocene with the arrival of paleo-Indians and the extinction of mastodon and horse. PMID- 17735195 TI - Spasmodic tremor and possible magma injection in long valley caldera, eastern california. AB - Intensive microearthquake swarms with the appearance of volcanic tremor have been observed in the southwest part of Long Valley caldera, southeastern California. This activity, possibly associated with magma injection, began 6 weeks after several strong (magnitude 6+) earthquakes in an area south of the caldera and has continued sporadically to the present time. The earthquake sequence and magmatic activity are part of a broad increase in tectonic activity in a 15,000-square kilometer region surrounding the "White Mountains seismic gap," an area with high potential for the next major earthquake in the western Great Basin. PMID- 17735196 TI - Biological Control of Yellow Nutsedge with the Indigenous Rust Fungus Puccinia canaliculata. AB - Yellow nutsedge (Cyperus esculentus L.) is a serious weed problem in the United States and other countries. An indigenous rust fungus [Puccinia canaliculata (Schw.) Lagerh.], pathogenic on yellow nutsedge, was released in early spring as a potential biological control agent. The fungus inhibited nutsedge flowering and new tuber formation. The fungus also dehydrated and killed nutsedge plants. The successful control of yellow nutsedge by a rust epiphytotic under experimental conditions demonstrates the potential use of the rust in an integrated weed management system. PMID- 17735197 TI - SCIENCE NEWS. PMID- 17735198 TI - SOME PRESENT-DAY PROBLEMS OF ZOOLOGY TEACHING. PMID- 17735201 TI - EVIDENCE OF A LOWER LEVEL OF LAKE SUPERIOR. PMID- 17735199 TI - PLANES OF LATERAL CORRASION. PMID- 17735200 TI - THE STRUCTURE OF SOME INDUSTRIAL DIAMONDS. PMID- 17735203 TI - BACTERIAL STEM-ROT DISEASE OF HYBRID SEEDLING CANES. PMID- 17735202 TI - THE FOUCAULT EXPERIMENT. PMID- 17735204 TI - A NEW SPRING BALANCE FOR MEASURING WATER CONTENT OF SNOW. PMID- 17735205 TI - COMPARISON BETWEEN IRRADIATION OF DIET AND SUPPLEMENTAL IRRADIATION OF ANIMALS IN VITAMIN A AND D DEFICIENCY. AB - The stimulating effects of the Vitamin D thus supplied became quite apparent and lasted for 10 days, then began to subside. The animals in Lot 2 were allowed to exist on the Sherman No. 380 diet, with supplemental Vitamin D, in the form of irradiated ergosterol, but in Lot 1 the animals were also irrradiated daily except Sundays, for 30 seconds, at a distance of 18 inches from a Macbeth carbon arc lamp. PMID- 17735207 TI - TWIST IN THE GRAIN OF CONIFEROUS TREES. PMID- 17735206 TI - HYDROGEN-ION CONCENTRATION OF THE ALIMENTARY TRACTS OF FOWL, CAT AND RABBIT. AB - Herein has been presented the results secured in determining the pH of the gastrointestinal tract of the hen, the rabbit and the cat by means of the quinhydrone electrode. PMID- 17735208 TI - Letters. PMID- 17735210 TI - Letters. PMID- 17735209 TI - Letters. PMID- 17735211 TI - Less than golden future. PMID- 17735212 TI - Polywater: homely and universal. PMID- 17735213 TI - "Friends" of the ecology movement. PMID- 17735214 TI - A time to take stock. PMID- 17735215 TI - Seeding cumulus in Florida: new 1970 results. AB - In the Florida single cloud experiments, the main result of the statistical analyses is that the dynamic seeding effect on rainfall is large, positive, and significant. From all the 1968 and 1970 data together, the seeding effect is estimated to be larger than a factor of 3; that is, the seeded clouds rained more than three times as much as the controls after the seeding run. On fair days, defined objectively by percentage of area covered by showers, the seeding effect is shown to be larger than the overall average, but it may be negative on rainy days. Rainy days in the tropics are about 10 percent of the days with rain, but they produce about half the total rainfall. The applicability of our single cloud results to other areas is not established but seems hopeful for many tropical and subtropical regions. It can be assessed by cloud population studies together with our numerical model (25). Guidance for the next steps toward practical rainfall enhancement and toward the understanding and modification of cloud systems in storms may be provided by our study of merger clouds. Mergers are shown often to produce more than an order of magnitude more rain than isolated clouds on the same day, probably owing to dynamic invigoration of the merged cloud circulations. Results of our first small attempt toward inducing and documenting mergers in a multiple cloud seeding experiment appear promising. Although far from statistically conclusive, they have opened a new frontier in the science and technology of dynamic cloud modification. It is also hoped that the multiple cumulus seeding experiments will help to clarify the formation of "cloud clusters" and their role in large-scale circulations, thus contributing to the focal subject of the Global Atmospheric Research Program in the tropics. PMID- 17735216 TI - Archeological methodology and remote sensing. AB - We have shown that the different spectral surveying techniques and the resultant imagery vary in their applicability to archeological prediction and exploration, but their applications are far broader than we have indicated. Their full potential, to a considerable extent, still remains unexplored. Table 1 is a chart of the more common sensor systems useful to archeological investigators. Several kinds of photography, thermal infrared imagery, and radar imagery are listed. Checks in various categories of direct and indirect utility in archeological research indicate that the different systems do provide varying degrees of input for studies in these areas. Photography and multispectral photography have the broadest applications in this field. Standard black-and-white aerial photography generally serves the purposes of archeological exploration and site analysis better than infrared scanner imagery, radar, or color photography. However, the real value of remotesensing experimentation lies in the utilization of different instruments and in the comparison and correlation of their data output. It can be stated without doubt that there is no one all-purpose remotesensing device on which the archeologist can rely that will reveal all evidence of human occupations. Remote-sensing data will not replace the traditional ground-based site survey, but, used judiciously, data gathered from aerial reconnaissance can reveal many cultural features unsuspected from the ground. The spectral properties of sites distinguishable by various types of remote sensors may perhaps be one of their most characteristic features, and yet the meaning of the differential discrimnination of features has not been determined for the most part, since such spectral properties are poorly understood at this date. The difficulty in isolating the causes of acceptable definition in certain portion of the spectrum and the lack of acceptable definition in others suggests that the evaluation of remote-sensing devices discussed in this article is not always applicable to all environmental zones at all times and for all types of cultural features. The uncontrollable variables of terrain, ground cover, weather, types of archeological manifestations, and other factors all play an important role in the utility of the imagery to the archeologist. Factors within the control of the photographer or archeolgist, such as altitude, position of the sun, and the direction of flight, can greatly influence the utility of the sensor data. In addition, the variables should not be considered solely as they affect resolution. Resolution, per se, although an important photogrammetric parameter of remote-sensing imagery, is by no means the only important factor in data analysis. The synoptic overview, which is provided by aerial imagery, is frequently as necessary in interpretation as the spotting and identification of individual cultural features. Stated more simply, we might say: "To understand, one most certainly must see the forest as well as the individual trees." For maximum data retrieval, it is necessary that the archeologist attempt to utilize as many different types of remote-sensing devices under as many variable seasonal and climatic conditions as his resources and skill will allow. Only then he can select the most efficient system for the purpose in his area of study. PMID- 17735217 TI - Scientific manpower for 1970-1985. PMID- 17735218 TI - San Fernando Earthquake Study: NRC Panel Sees Premonitory Lessons. PMID- 17735219 TI - Aid for jobless scientists. PMID- 17735220 TI - Plutonium: reactor proliferation threatens a nuclear black market. PMID- 17735221 TI - IAEA and Non-Proliferation of a Nuclear Black Market. PMID- 17735222 TI - Eocene volcanism and the origin of horizon a. AB - A series of closely time-equivalent deposits that correlate with seismic reflector horizon A exists along the coast of eastern North America. These sediments of Late-Early to Early-Middle Eocene age contain an authigenic mineral suite indicative of the alteration of volcanic glass. A volcanic origin for these siliceous deposits onshore is consistent with a volcanic origin for the cherts of horizon A offshore. PMID- 17735223 TI - Cosmic-ray tracks in plastics: the apollo helmet dosimetry experiment. AB - Counts of tracks from heavy cosmic-ray nuclei in helmets from Apollo missions 8 and 12 show variations caused by solar modulation of the galactic cosmic-ray flux. Specific estimates of the biological damage to certain nonreplaceable cells by track-forming particles during these space missions indicate that the fraction of deactivated cells could range from a lower limit of 3 x 10(-7) to an upper limit of 1.4 x 10(-4). PMID- 17735224 TI - Geomagnetic Reversals during the Phanerozoic. AB - An antalysis of worldwide paleomagnetic measurements suggests a periodicity of 350 x 10(6) years in the polarity of the geomagnetic field. During the Mesozoic it is predominantly normal, whereas during the Upper Paleozoic it is predominantly reversed. Although geomagnetic reversals occur at different rates throughout the Phanerozoic, there appeaars to be no clear correlation between biological evolutionary rates and reversal frequency. PMID- 17735225 TI - Lunar anorthosites: plagioclase crystallization. PMID- 17735227 TI - Yellow Fever research. PMID- 17735226 TI - In reply: yellow Fever research. PMID- 17735228 TI - And the clocks are striking one. PMID- 17735229 TI - Computer-based instructional dialogs in science courses. AB - The personal computer is opening the door to supplemental, essentially tutorial, modes of science instruction that, particularly at introductory levels, can significantly enhance understanding of science and develop abstract reasoning skills. Competently prepared and judiciously utilized materials have the potential to improve the education of science and engineering professionals, elementary and secondary teachers, and, to some degree, the public at large. PMID- 17735231 TI - House Votes Florida State a Supercomputer: Support from the chairman of the science and technology committee, whose district includes the university, played a key role. PMID- 17735230 TI - More for catholic, columbia. PMID- 17735232 TI - Georgetown seeks $160 million. PMID- 17735234 TI - EPA overhauls pesticide office. PMID- 17735233 TI - New Worries About Space Telescope: Spare parts, maintenance, and refurbishment may be more complex and more expensive than anyone has realized. PMID- 17735235 TI - Appeals court upholds legal block on experiment. PMID- 17735237 TI - Western academies seek help for sakharov. PMID- 17735236 TI - Creationism defeated in louisiana senate. PMID- 17735238 TI - Patents Encroaching on Research Freedom: A tradition of disregarding patent infringement when it involves experimental use of an invention may be eroding for biologists. PMID- 17735240 TI - Crystal Anisotropy Directs Solidification: Simplified mathematical models of solidification elevate crystalline anisotropy to main player in selecting dendritic growth patterns. PMID- 17735239 TI - DOD Springs Surprise on Secrecy Rules. PMID- 17735241 TI - Cold-climate foragers: boreal forest adaptations. PMID- 17735243 TI - An organization of engineers: 75 years of progress. PMID- 17735242 TI - Audition: hearing. PMID- 17735244 TI - The European quaternary: glacial deposits in north-west europe. PMID- 17735245 TI - Mississippi deltaic wetland survival: sedimentation versus coastal submergence. AB - Seasonal sedimentation, measured with the aid of artificial marker horizons, was markedly different in deteriorating as compared with stable marshes in the Mississippi River deltaic plain. Deteriorating marshes receive most sediment during storm events, whereas stable marshes receive substantial amounts of sediments during the spring river flood. The deteriorating marshes are accreting at a faster rate (1.5 centimeters per year at streamside, 0.9 centimeter per year at inland areas) than the stable marshes (1.3 centimeters per year at streamside, 0.6 centimeter per year at inland areas). However, relative to local apparent sea level rise as measured by tide gauges in each area, the deteriorating marshes are not maintaining their intertidal elevation as well as the stable marshes. These results indicate the importance of considering accretion relative to submergence. PMID- 17735246 TI - Growth Stasis and Limited Shell Calcification in Larvae of Cymatium parthenopeum During Trans-Atlantic Transport. AB - Larvae of the shallow-water marine gastropod Cymatium parthenopeum show no appreciable shell calcification and no demonstrable growth as they disperse across the Atlantic Ocean. Evidence of what appears to be physiological specialization for prolonged delay of metamorphosis was found in larvae of this prosobranch gastropod. PMID- 17735247 TI - The appearance of sustained equatorial surface westerlies during the 1982 pacific warm event. AB - In June 1982 a band of anomalous southerly surface wind, extending from the equator as far south as the Tasman Sea, formed east of Australia (150 degrees E to 160 degrees E). This flow crossed the equator just before the appearance of sustained westerly winds on the equator somewhat west of the date line. Because these westerly winds induced the initial strong equatorial warming of the ocean east of the date line during the 1982 El Nino-Southern Oscillation (ENSO) event, the southerly jet appears to be an important atmospheric component leading to the onset of the vigorous phase of this event. Some historical evidence suggests that anomalous southerly winds in the same region occurred prior to the appearance of sustained equatorial westerly winds in the major ENSO events of 1957, 1965, and 1972. PMID- 17735249 TI - ON MODIFICATION AND VARIATION. PMID- 17735248 TI - Formaldehyde risk assessment. PMID- 17735250 TI - NATURE STUDY AND INTELLECTUAL CULTURE. PMID- 17735251 TI - THE FATE OF A EUROPEAN BISON HERD. PMID- 17735252 TI - DENTITION OF LEMURS AND THE SYSTEMATIC POSITION OF TARSIUS. PMID- 17735253 TI - CURRENT NOTES ON PHYSIOGRAPHY. PMID- 17735254 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17735256 TI - SCIENCE, DEMOCRACY AND THE UNIVERSITY. PMID- 17735255 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17735257 TI - ASTRONOMICAL NOTES. PMID- 17735259 TI - ACADEMIC FREEDOM IN RUSSIA. PMID- 17735258 TI - SYSTEMATIC ZOOLOGY. PMID- 17735260 TI - AGE OF THE ISLAND SERIES. PMID- 17735261 TI - THE DATE OF PUBLICATION. PMID- 17735262 TI - GLACIERS IN THE MONTANA ROCKIES. PMID- 17735263 TI - INTERNATIONAL COOPERATION IN AERONAUTICS. PMID- 17735265 TI - Dialog on the future of agriculture. PMID- 17735264 TI - This week in science. PMID- 17735266 TI - In reply: cold fusion at Texas a&m. PMID- 17735267 TI - In reply: cold fusion at Texas a&m. PMID- 17735268 TI - Cold fusion at Texas a&m. PMID- 17735269 TI - In reply: cold fusion at Texas a&m. PMID- 17735270 TI - Erratum. AB - Beth A. Snyder, not Ralph L. Nicholson, should have received credit for the cover photograph of 29 June 1990. PMID- 17735271 TI - In reply: viral etiology of AIDS and the gallo probe. PMID- 17735273 TI - SSC Cost Esimates Climb. PMID- 17735272 TI - Listing to starboard: the Oregon formula. PMID- 17735274 TI - Doing science at the gates of hell. PMID- 17735275 TI - Chinese still coming. PMID- 17735276 TI - Yet another job for wyngaarden. PMID- 17735277 TI - Bick replacement named. PMID- 17735278 TI - How to perform a meta-analysis. PMID- 17735280 TI - The greenhouse consensus. PMID- 17735279 TI - Richard peto: statistician with a mission. PMID- 17735281 TI - New Greenhouse Report Puts Down Dissenters: An international panel assessing greenhouse warming pointedly denies the validity of objections raised by a prominent minority. PMID- 17735282 TI - From force fields to dynamics: classical and quantal paths. AB - Reaction path methods provide a powerful tool for bridging the gap between electronic structure and chemical dynamics. Classical mechanical reaction paths may usually be understood in terms of the force field in the vicinity of a minimum energy path (MEP). When there is a significant component of hydrogenic motion along the MEP and a barrier much higher than the average energy of reactants, quantal tunneling paths must be considered, and these tend to be located on the corner-cutting side of the MEP. As the curvature of the MEP in mass-scaled coordinates is increased, the quantal reaction paths may deviate considerably from the classical ones, and the force field must be mapped out over a wider region, called the reaction swath. The required force fields may be represented by global or semiglobal analytic functions, or the dynamics may be computed "directly" from the electronic structure results without the intermediacy of potential energy functions. Applications to atom and diatom reactions in the gas phase and at gas-solid interfaces and to reactions of polyatomic molecules in the gas phase, in clusters, and in aqueous solution are discussed as examples. PMID- 17735284 TI - Chaos rampant. PMID- 17735283 TI - The energetic cost of limbless locomotion. AB - The net energetic cost of terrestrial locomotion by the snake Coluber constrictor, moving by lateral undulation, is equivalent to the net energetic cost of running by limbed animals (arthropods, lizards, birds, and mammals) of similar size. In contrast to lateral undulation and limbed locomotion, concertina locomotion by Coluber is more energetically expensive. The findings do not support the widely held notion that the energetic cost of terrestrial locomotion by limbless animals is less than that of limbed animals. PMID- 17735285 TI - Health treatment for torture survivors. PMID- 17735286 TI - Malaria strategies for Africa. PMID- 17735287 TI - Science and black churches. PMID- 17735288 TI - Seen Any Good TV Lately? PMID- 17735289 TI - SWARM Division Prizes for Students. PMID- 17735291 TI - German National Socialism and the Quest for Nuclear Power, 1939-1949. Mark Walker. Cambridge University Press, New York, 1989. x, 290 pp., illus. $29.95. PMID- 17735290 TI - Public science day 1991. PMID- 17735292 TI - Recollections of My Life. Santiago Ramon Y Cajal. MIT Press, Cambridge, MA, 1989. xxvi, 638 pp., illus. Paper, $16.95. Translated from the third Spanish edition (1923). Reprint, 1937 edition; The Never-Ceasing Search. Francis O. Schmitt. American Philosophical Society, Philadelphia, 1990. xvi, 399 pp., illus. $30. Memoirs of the American Philosophical Society, vol. 188; Song Among the Ruins. William J. Schull. Harvard University Press, Cambridge, MA, 1990. x, 305 pp. + plates. $25; Science, Churchill, and Me. Hermann Bondi. Pergamon, New York, 1990. x, 142 pp. + plates. $30; A Very Decided Preference. Life with Peter Medawar. Jean Medawar. Norton, New York, 1990. 256 pp., illus. $19.95; Landau. The Physicist and the Man. I. M. Khalatnikov, Ed. Pergamon, New York, 1989. viii, 323 pp., illus. $100. Translated from the Russian by J. B. Sykes; Chandrasekhara Venkata Raman. A. Jayaraman. Allied East-West Press, New Delhi, 1989 (available from the author, AT&T Bell Laboratories, Murray Hill, NJ 07974). xiv, 214 pp. + plates. $10; paper, $8. PMID- 17735293 TI - Stress Proteins In Biology and Medicine. Richard I. Morimoto, Alfred Tissieres, and Costa Georgopoulos, Eds. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 1990. x, 450 pp., illus. $97. Cold Spring Harbor Monograph Series 19. PMID- 17735294 TI - The Art of Measurement. Metrology in Fundamental and Applied Physics. Bernhard Kramer, Ed. VCH, New York, 1989. xiv, 335 pp., illus. $66. Research--Measurement- Approval. From a symposium, Berlin, F.R.G., 1987. PMID- 17735296 TI - CENTENARIANS IN FRANCE. PMID- 17735295 TI - Products & materials. PMID- 17735298 TI - SCHOOL-WORK AND EYESIGHT. PMID- 17735297 TI - THE TOPOGRAPHIC MAP OF NEW JERSEY. PMID- 17735299 TI - TISSOT'S THEORY OF THE PROJECTION OF MAPS. PMID- 17735301 TI - COMMERCIAL GEOGRAPHY. PMID- 17735300 TI - ELECTRICAL SCIENCE. PMID- 17735302 TI - HEALTH MATTERS. PMID- 17735303 TI - ETHNOLOGY. PMID- 17735305 TI - Dream Excitation. PMID- 17735306 TI - Credit in Education? PMID- 17735304 TI - Chemical Action between Solids. PMID- 17735307 TI - Can We Halt the Race for Atomic Arms? PMID- 17735308 TI - Note on Absolute Chronology of Human Evolution. PMID- 17735309 TI - Chlorosis Produced by Fluorine on Citrus in Florida. PMID- 17735310 TI - Temperature Control in the Measurement of Particle Volumes by the Isopiestic Method. PMID- 17735311 TI - Photochemical Reactions of Nitrogen Dioxide and Hydrocarbons in Air. PMID- 17735313 TI - Some Potassium-Argon Ages for Western Canada. PMID- 17735312 TI - Chinese Walls of New Cave, Carlsbad Caverns National Park. PMID- 17735314 TI - Miscellaneous Publications. PMID- 17735316 TI - Scientific Meetings. PMID- 17735318 TI - The image of sociobiology. PMID- 17735317 TI - Resistance management. PMID- 17735319 TI - Response:interpretations of multiregional evolution. PMID- 17735321 TI - This week in Science. PMID- 17735320 TI - Mona with cigar? PMID- 17735322 TI - Federal project funding. PMID- 17735323 TI - In reply: research costs. PMID- 17735324 TI - Waste management. PMID- 17735325 TI - Imaging spectrometry for Earth remote sensing. AB - Imaging spectrometry, a new technique for the remote sensing of the earth, is now technically feasible from aircraft and spacecraft. The initial results show that remote, direct identification of surface materials on a picture-element basis can be accomplished by proper sampling of absorption features in the reflectance spectrum. The airborne and spaceborne sensors are capable of acquiring images simultaneously in 100 to 200 contiguous spectral bands. The ability to acquire laboratory-like spectra remotely is a major advance in remote sensing capability. Concomitant advances in computer technology for the reduction and storage of such potentially massive data sets are at hand, and new analytic techniques are being developed to extract the full information content of the data. The emphasis on the deterministic approach to multispectral data analysis as opposed to the statistical approaches used in the past should stimulate the development of new digital image-processing methodologies. PMID- 17735326 TI - Annual heat balance of martian polar caps: viking observations. AB - The Infrared Thermal Mappers aboard the two Viking orbiters obtained solar reflectance and infrared emission measurements of the Martian north and south polar regions during an entire Mars year. The observations were used to determine annual radiation budgets, infer annual carbon dioxide frost budgets, and constrain spring season surface and atmospheric properties with the aid of a polar radiative model. The results provide further confirmation of the presence of permanent CO(2)frost deposits near the south pole and show that the stability of these deposits can be explained by their high reflectivities. In the north, the observed absence of solid CO(2) during summer was primarily the result of enhanced CO(2) sublimation rates due to lower frost reflectivities during spring. The results suggest that the present asymmetric behavior of CO(2)frost at the Martian poles is caused by preferential contamination of the north seasonal polar cap by atmospheric dust. PMID- 17735328 TI - Academy proposes a federal trauma center. PMID- 17735327 TI - Hughes Institute Poised for Growth: The imminent sale of Hughes Aircraft for billions of dollars will make the Hughes Medical Institute an awesome philanthropy. PMID- 17735329 TI - Dispute reopened on mysterious 1979 flash. PMID- 17735330 TI - NRC Considers Dropping University Reactor Rule. PMID- 17735331 TI - California Gears Up to Bid for the SSC. PMID- 17735332 TI - Industry wary of tech transfer bills. PMID- 17735333 TI - Where Are the Dead Quasars?: Two recent observations suggest that many "ordinary" galaxies--including our own--contain ultramassive black holes. PMID- 17735334 TI - Chaotic zone yields meteorites. PMID- 17735335 TI - Issues of allometry: size and scaling in primate biology. PMID- 17735336 TI - Quantum chemistry: the quantum theory of unimolecular reactions. PMID- 17735337 TI - The liquid state: theory of molecular fluids. PMID- 17735338 TI - Theoretical physics: theoretical concepts in physics. PMID- 17735339 TI - The detection of eclipses in the pluto-charon system. AB - The first eclipses between Pluto and its satellite ("Charon") were detected in January and February 1985, confirming the satellite's existence. Eclipses lasting a few hours will now occur at 3.2-day intervals for the next 5 to 6 years and then will cease for about 120 years. Careful observations of these eclipses will allow greatly improved determinations to be made of several physical parameters for the Pluto-Charon system: the diameters of the planet and satellite, the surface albedo distribution on one hemisphere of the planet, the orbit of the satellite, and the mass of the planet and hence its density. Knowledge of the density will provide a constraint on models of Pluto's bulk composition. PMID- 17735340 TI - SCIENCE NEWS. PMID- 17735341 TI - ENGINEERING CULTURE. PMID- 17735342 TI - SCIENTIFIC AND PHILOSOPHICAL METHODS IN EDUCATION. PMID- 17735343 TI - THE BARRINGER METEORITE. PMID- 17735344 TI - CONCERNING THE RATE OF FORMATION OF STALACTITES. PMID- 17735345 TI - AN ENGINEER IN AUTHORITY. PMID- 17735347 TI - THE LANGUAGE OF CLERGYMEN. PMID- 17735346 TI - BABYLONIAN MATHEMATICS. PMID- 17735348 TI - EXHIBITION ON THE SCIENCE AND ART OF COLOR. PMID- 17735350 TI - A NEW MICRO-MANIPULATOR. PMID- 17735349 TI - ANTI-EVOLUTION LAWS. PMID- 17735351 TI - OVULATION, OESTRUS AND COPULATION WITH CONSEQUENT DYSTOCIA DURING PREGNANCY, IN THE MOUSE. PMID- 17735353 TI - CHANGES OCCURRING IN STORED ALCOHOLIC PLANT EXTRACTS. PMID- 17735352 TI - DETERMINATE EVOLUTION IN THE GENUS SPIRIFER. PMID- 17735354 TI - SCIENCE NEWS. PMID- 17735356 TI - DEFINITIONS OF THE MATHEMATICAL TERM GROUP. PMID- 17735355 TI - RECENT TRENDS IN THE HUMANITIES. PMID- 17735357 TI - A NAME FOR BIO-HYDRAULIC ACTIVITIES. PMID- 17735358 TI - ANTECEDENT LIGHTNING PROTECTION. PMID- 17735359 TI - DIPLONEURA NITIDULA MEIGEN. PMID- 17735360 TI - PLEOSPORA LYCOPERSICI E. AND E. MARCH., A TOMATO PATHOGEN IN THE UNITED STATES. PMID- 17735361 TI - AN EXPEDITION TO HAINAN. PMID- 17735362 TI - ANTHROPOLOGICAL EXPEDITION TO THE NORTHWEST OF SOUTH AUSTRALIA. PMID- 17735363 TI - BEYOND URANIUM WITH THE MAGNETOOPTIC METHOD OF ANALYSIS. PMID- 17735365 TI - A SECOND METHOD OF CONTRACTION IN THE STRIATED MUSCLE OF SOME VERTEBRATE ANIMALS. PMID- 17735364 TI - ELECTRICAL EXCITATION OF THE NERVOUS SYSTEM--INTRODUCING A NEW PRINCIPLE: REMOTE CONTROL. PRELIMINARY REPORT. PMID- 17735366 TI - A NEW TYPE OF BROAD BASE TERRACE. PMID- 17735367 TI - A NON-BITTER VARIETY OF MELILOTUS. PMID- 17735368 TI - An Institute of Microbiology--Its Aims and Purposes. PMID- 17735369 TI - On the Interpretation of the Absorption of Ultraviolet Light by Cellular Nucleic Acids. PMID- 17735370 TI - The Application of the Beer-Lambert Law to Optically Anisotropic Systems. PMID- 17735371 TI - Chromosome Numbers for Two Species of Mexican Commelinaceae. PMID- 17735372 TI - Opalescence of Serum after Total Body X-Irradiation as a Prognostic Sign of Death. PMID- 17735373 TI - An Automatic Analyzer for the Study of Speech in Interaction and in Free Association. PMID- 17735374 TI - Increasing the Efficiency of the Laying Hen. PMID- 17735376 TI - Age of Canada's Principal Gold-producing Belt. PMID- 17735375 TI - Low Temperature and Survival of Embryonic Tissue. PMID- 17735377 TI - Replanting Discarded Varieties as a Means of Disease Control. PMID- 17735378 TI - Some Simple Calculations Concerning the Efficiency of the Photosynthetic Mechanism. PMID- 17735379 TI - William John Dann 1904-1948. PMID- 17735380 TI - Paul Rode 1901-1948. PMID- 17735381 TI - ESP Research. PMID- 17735382 TI - ESP Research. PMID- 17735383 TI - Radwaste policy. PMID- 17735384 TI - The numbers game. PMID- 17735386 TI - Honoring albert einstein. PMID- 17735385 TI - ESP Research. PMID- 17735388 TI - Is founder of modern anatomy subject of mysterious portrait? PMID- 17735387 TI - Iron ore: energy, labor, and capital changes with technology. AB - Resource gathering is depending on leaner crude ores. Iron ore mining typifies this trend. To make lean taconite iron ores useful required a technologic breakthrough-pelletization. The shift to iron ore pellets has the advantage that they require less energy and labor per ton of molten iron than high-grade naturally concentrated ores. Increased reliance on pellets causes a geographic shift of some jobs and environmental effects from blast furnaces to iron ore mines. PMID- 17735390 TI - Anti-semitism alleged in soviet mathematics. PMID- 17735389 TI - Dioxins have been present since the advent of fire, says dow. PMID- 17735391 TI - A program to aid soviet jewish mathematicians. PMID- 17735393 TI - Energy facility siting seen in need of reform. PMID- 17735392 TI - Utility industry is cool to voltage reduction project. PMID- 17735394 TI - Nader Queries Handler on Status of CONAES Study. PMID- 17735396 TI - The 1978 nobel prize in chemistry. PMID- 17735395 TI - Doppler radar: new look into violent weather. PMID- 17735397 TI - Early experiences and behavior. PMID- 17735399 TI - The ocean-atmosphere system. PMID- 17735398 TI - Anaerobic plants. PMID- 17735400 TI - Chromatin structure. PMID- 17735401 TI - Early deglaciation of the labrador shelf. AB - Two marine sediment cores from a basin on the southeastern Labrador Shelf penetrate a mud sequence extending back to 21,000 carbon-14 years before the present (B.P.). The benthic foraminifera are dominated by subartic nearshore species indicative of ice-free summer waters. The pollen record indicates the presence of a sedge-shrub tundra in eastern Labrador as early as 21,000 years B.P. Both sources of evidence suggest less extensive continental ice than has previously been reported for this subarctic region. PMID- 17735403 TI - Ozone formation related to power plant emissions. AB - A curious and unambiguous event of excess ozone formation downwind of a power plant has been analyzed. A kinetic model used to simulate the event indicates that the excess ozone can be reconciled entirely on the basis of excess nitrogen oxides in the polluted air. PMID- 17735402 TI - Carbon flow in four lake ecosystems: a structural approach. AB - Direct and indirect carbon fluxes in lakes Marion (British Columbia), Findley (Washington), Wingra (Wisconsin), and Mirror (New Hampshire) are compared, using budgets and input-output analysis. Overall differences in carbon flow between the lakes are shown with cycling indices of .031, .108, .572, and .661, respectively. The results suggest that lake ecosystems may be considered unique aggregatins of similar components. PMID- 17735404 TI - Polychlorinated biphenyls: transfer from microparticulates to marine phytoplankton and the effects on photosynthesis. AB - Polychlorinated biphenyls (PCB's) initially associated with microparticulates are incorporated into marine diatom cells. The time course of transfer is rapid; equilibrium is attained within several hours. Assays with chlorophyll a fluorescence in vivo indicate that the transferred PCB's reach sites in the photosynthetic machinery that are sensitive to the effects of these compounds. PMID- 17735405 TI - Phanerozoic peridotitic and pyroxenitic komatiites from newfoundland. AB - Peridotitic and highly magnesian pyroxenitic komatiites, thus far known to occur almost exclusively in the Archean (before 2.5 x 10(9) years ago) terranes, are reported from an Ordovician (0.5 x 10(9) years) ophiolite suite in Newfoundland. Their occurrence as pillow lavas or as chilled dikes, their possession of quench textures and geochemical parameters such as high contents of magnesium oxide, nickel, and chromium and low contents of titanium dioxide and potassium monoxide, low ratios of iron to iron plus magnesium, and values of the ratio of calcium oxide to aluminum oxide of close to unity demonstrate that they were formed through the rapid cooling of a highly mobile komatiitic melt. These features resemble those of many Archean peridotitic-pyroxenitic komatiites and indicate that the Archean-type magmatism did prevail in the younger segments of the earth's history although perhaps in a more erratc manner. PMID- 17735406 TI - r and K Selection in Experimental Populations of Escherichia coli. AB - Populations were adapted in vitro under density-dependent and density-independent population controls. Comparison of strains fails to demonstrate any trade-off in adaptation under these population controls. PMID- 17735407 TI - 6-hydroxydopamine and anticholinergic drugs. PMID- 17735408 TI - Carnivoran jaw shape. PMID- 17735410 TI - Politics and science. PMID- 17735409 TI - Carnivoran jaw shape. PMID- 17735411 TI - Politics and science. PMID- 17735412 TI - Internet access. PMID- 17735413 TI - Internet access. PMID- 17735415 TI - Internet access. PMID- 17735414 TI - Internet access. PMID- 17735416 TI - Nile delta erosion. PMID- 17735417 TI - New database. PMID- 17735419 TI - Does macroscopic quantum coherence occur in ferritin? PMID- 17735418 TI - DOE Privatization. PMID- 17735420 TI - Does macroscopic quantum coherence occur in ferritin? PMID- 17735422 TI - AN ILLUSTRATION OF AN ABUSE. PMID- 17735421 TI - Response: does macroscopic quantum coherence occur in ferritin? PMID- 17735423 TI - THE DRY- AND WET-BULB HYGROMETER. PMID- 17735424 TI - A STUDY OF THE HUMAN TEMPORAL BONE.--III. PMID- 17735425 TI - THE NAPLES ZOOLOGICAL STATION. PMID- 17735427 TI - EARLY DEVELOPMENT OF REPTILES. PMID- 17735426 TI - EVIDENCES OF GLACIATION IN KENTUCKY. PMID- 17735428 TI - THE INTERNATIONAL GEOLOGICAL CONGRESS. PMID- 17735429 TI - Intelligence of the crow. PMID- 17735430 TI - Nemestrinidae. PMID- 17735431 TI - Rainbow. PMID- 17735433 TI - STUDIES IN LOGIC. PMID- 17735432 TI - DEVELOPMENT OF THE MEMBRANE-BONES OF THE SKULL OF THE PIKE. PMID- 17735434 TI - THE RACES OF MEN. PMID- 17735435 TI - GAGE'S ELEMENTS OF PHYSICS. PMID- 17735436 TI - INTELLIGENCE FROM AMERICAN SCIENTIFIC STATIONS. PMID- 17735437 TI - ETHNOLOGICAL NOTES. PMID- 17735438 TI - HEALTH MATTERS. PMID- 17735440 TI - THE UPRIGHT POSITION IN MAN. PMID- 17735439 TI - FLORIDA GEOLOGICAL SURVEY. PMID- 17735441 TI - RELATION OF THE STATE TO INDUSTRIAL ACTION. PMID- 17735442 TI - GRASSES OF NORTH AMERICA. PMID- 17735443 TI - PHYSICAL SCIENCE IN THE SECONDARY SCHOOLS. PMID- 17735445 TI - CONTRIBUTIONS FROM THE LABORATORY OF THE YORK COLLEGIATE INSTITUTE. PMID- 17735444 TI - OUR VACANT PUBLIC LANDS. PMID- 17735446 TI - CURRENT NOTES ON ANTHROPOLOGY.-XXVI. PMID- 17735448 TI - SECRETS OF THE ATMOSPHERE. PMID- 17735447 TI - THE HIEROGLYPHICS AND SYMBOLS OF ANCIENT MEXICO. PMID- 17735449 TI - GLACIATION IN AUSTRALIA. PMID- 17735450 TI - LOSS OF DRY MATTER BY THE SPROUTING OF CORNSEEDS. PMID- 17735451 TI - Pre-Historic Remains in America. PMID- 17735452 TI - Early Attempts at Storm-Warning. PMID- 17735453 TI - ELECTRICAL NOTES. PMID- 17735454 TI - The Palaeolithic Man Once More. PMID- 17735455 TI - Auroras. PMID- 17735457 TI - McGovern's Conversion Program. PMID- 17735456 TI - IQ: Methodological and Other Issues. PMID- 17735458 TI - Letter to the editor. PMID- 17735459 TI - Letter to the editor. PMID- 17735460 TI - Letter to the editor. PMID- 17735462 TI - Letter to the editor. PMID- 17735461 TI - Letter to the editor. PMID- 17735463 TI - Letter to the editor. PMID- 17735465 TI - Unemployed engineers. PMID- 17735464 TI - Letter to the editor. PMID- 17735466 TI - Old-fashioned virtues. PMID- 17735468 TI - Project sanguine. PMID- 17735467 TI - A philosophy for technology. PMID- 17735470 TI - Sickle cell anemia: national program raises problems as well as hopes. PMID- 17735469 TI - Electronic Characterization of Solid Surfaces: Determination of the energy levels of electrons at surfaces is now possible over a wide energy range. AB - At this point it would be presumptuous to suggest either that we understand very much about the electronic structure of solid surfaces or that we can specify in detail exactly what each of our tools for studying such structure is telling us. I think it is fair to say, however, that FES, UPS, and INS do make it possible for us to determine energy level spectra which can with some confidence be ascribed to the resonances of electrons in surface orbitals. It is true that INS is the more surface-selective of the two electron spectroscopies capable of producing data over at least a 10-ev energy range. We have seen intriguing differences between INS and UPS which, when we come to understand them, will most certainly reveal important characteristics of surface electronic structure and greatly expand our ability to distinguish electronic states in the surface from those in the selvedge. Possibly it is not too much to hope that the combined use of INS and UPS with incidence angle as an independent variable will give us information on the geometrical extent of surface orbitals, as well as the net electrical charge and the electric potential gradient in the region of the surface in which the orbitals lie. PMID- 17735471 TI - Turnover at CEQ. PMID- 17735472 TI - SIPRI: Peace Research Institute Losing Old Staff, Pondering Role. PMID- 17735473 TI - Medicine at Michigan State (III): Conditioning for Innovation. PMID- 17735474 TI - First nonmedical chinese scientists to visit u.s. PMID- 17735475 TI - Magnetic containment fusion: what are the prospects? PMID- 17735476 TI - Eastern Atlantic Continental Margin: Some Results of the 1972 Cruise of the R.V. Atlantis II. AB - A geophysical survey of the southeastern Atlantic Ocean has been made as one of the programs of the International Decade of Ocean Exploration. A large ancient delta of the Orange River and a diapiric field off Angola were mapped. Both features were initiated during early stages of the separation of Africa and South America, and both may be potential sources of oil. PMID- 17735477 TI - Ridge transform fault spreading pattern in freezing wax. AB - A laboratory experiment shows that ridge-ridge transform faults, inactive fracture zones, and other features characteristic of spreading oceanic ridges can be produced in a variety of paraffins. Although the resultant pattern depends upon the temperature of the wax and the ratio of spreading rate to surface cooling, the characteristic orthogonal ridge transform fault system is a preferred mode of separation. Symmetric spreading occurs under conditions of no tensile strength across the ridge, and the stability of transform faults is a consequence of their lack of shear strength. The experiment also shows that properties characteristic of oceanic ridges occur under conditions of passive convection where upwelling of material at the ridge crest is a result only of hydrostatic forces in the fluid; that is, the plate separation is caused not by large convective forces beneath the ridge but rather by tensile forces in the plate. PMID- 17735478 TI - Environmental sciences. PMID- 17735479 TI - MEDICAL EDUCATION IN THE UNITED STATES. PMID- 17735481 TI - ECOLOGY. PMID- 17735482 TI - ARE STAMIENS AND PISTILS SEXUAL ORGANS? PMID- 17735480 TI - THE RARE EARTH CRUSADE; WHAT IT PORTENDS, SCIENTIFICALLY AND TECHNICALLY. PMID- 17735483 TI - PATAGONIAN GEOLOGY. PMID- 17735484 TI - GENERAL JAMES T. STRATTON. PMID- 17735485 TI - COMMENT AND CRITICISM. PMID- 17735486 TI - The most economical size of electric-lighting conductors. PMID- 17735487 TI - The functions of experiment-stations. PMID- 17735489 TI - THE CHEMICAL LABORATORY OF THE JOHNS HOPKINS UNIVERSITY. PMID- 17735488 TI - Sun-spots. PMID- 17735490 TI - LETTERS TO THE EDITOR. PMID- 17735491 TI - On the care of entomological museums. PMID- 17735492 TI - THE TILE-FISH. PMID- 17735493 TI - COMETS AND ASTEROIDS OF 1884. PMID- 17735495 TI - THE CHOLERA EPIDEMIC IN PARIS AND IN YPORT. PMID- 17735494 TI - FURTHER NOTES ON BOGOSLOFF ISLAND. PMID- 17735496 TI - AN AMERICAN COMMUNE. PMID- 17735497 TI - THE PHYSIOLOGICAL ANATOMY OF PLANTS. PMID- 17735498 TI - TROWBRIDGE'S PHYSICS. PMID- 17735499 TI - The Fifth Anniversary of Paricutin. PMID- 17735501 TI - George Grant MacCurdy 1863-1947. PMID- 17735500 TI - Experimental Research Into Psychosomatic Phenomena in Medicine. PMID- 17735502 TI - Symposium on Problems of the Earth's Gaseous Envelope. PMID- 17735503 TI - National Science Foundation--A Peril or a Hope? PMID- 17735504 TI - A Useful Prefix for the Extension of a Systematic Nomenclature for Intact Polycyclic to Related Open-Ring Systems. PMID- 17735505 TI - Studies on Hypoproteinemia: III. Lymphoid Hyperplasia and Redistribution of Nitrogen Caused in Mice by Transplanted Tumors (Sarcoma 180 and Breast Adenocarcinoma EO 771). PMID- 17735506 TI - Zeeman Effect and g-Values for Neutral Nitrogen and Oxygen. PMID- 17735508 TI - The Relation of Backscattering to Self-Absorption in Routine Beta-Ray Measurements. PMID- 17735507 TI - Multicellular Hairs in Gossypium. PMID- 17735509 TI - L-Penicillamine as a Metabolic Antagonist. PMID- 17735510 TI - Simple Preparation of Transparent Scales. PMID- 17735511 TI - Preparation of Standard Films of DDT Crystals for Toxicity Studies. PMID- 17735512 TI - Continuous Recording of Body Temperatures of Mice. PMID- 17735513 TI - A Method of Securing Living Mosquitoes to Mounts in Studies of Problems Concerning Flight. PMID- 17735515 TI - Meetings & Conferences. PMID- 17735514 TI - Mathematical Biology. PMID- 17735516 TI - Scientific Manpower. PMID- 17735517 TI - The Reservist Problem. PMID- 17735518 TI - DISEASE OF THE HEART. PMID- 17735519 TI - A. D. E. ELMER. PMID- 17735520 TI - CONFERENCE ON RESEARCH AND REGIONAL WELFARE. PMID- 17735521 TI - THE IMPERIAL COLLEGE OF SCIENCE AND TECHNOLOGY. PMID- 17735523 TI - THE DEPARTMENT OF TECHNOLOGY OF THE CARNEGIE LIBRARY OF PITTSBURGH. PMID- 17735522 TI - THE FIFTIETH ANNIVERSARY OF THE NEW YORK BOTANICAL GARDEN. PMID- 17735524 TI - A NEWLY DISCOVERED PERIODICITY OF 16 MONTHS IN THE SUN'S WAVE RADIATION. PMID- 17735525 TI - CENTENNIAL OF WOOD'S "CLASS-BOOK OF BOTANY". PMID- 17735526 TI - QUININE FROM REMIJIA BARK. PMID- 17735527 TI - SCIENCE AND THE NEW DRAFT REGULATIONS. PMID- 17735528 TI - TECHNOLOGICAL MANPOWER. PMID- 17735529 TI - GROWTH-RETARDING EFFECT OF CORN IN NICOTINIC ACID-LOW RATIONS AND ITS COUNTERACTION BY TRYPTOPHANE. AB - Either 50 mg 1(-)tryptophane or 1.0 mg nicotinic acid per 100 gms of ration completely counteracts the growth retardation caused by the inclusion of 40 per cent. corn grits in a low protein ration. A possible explanation of this observation is discussed. PMID- 17735530 TI - POLIOMYELITIS VIRUS IN FLY-CONTAMINATED FOOD COLLECTED AT AN EPIDEMIC. AB - Poliomyelitis virus has been detected in food exposed to flies at homes of poliomyelitis patients within an epidemic area. This was achieved by feeding such exposed food to chimpanzees which developed subclinical infections or asymptomatic carrier states ascertained by positive stool tests in rhesus monkeys. PMID- 17735532 TI - FILTRATION OF CITRATED PLASMA. AB - Large amounts of fresh citrated plasma can be filtered easily through specially prepared asbestos-composition pads without clotting. A description of the technique is given. PMID- 17735531 TI - THE EFFECT OF DIETARY PROTEIN INTAKE ON THE XANTHINE OXIDASE ACTIVITY OF RAT LIVER. PMID- 17735534 TI - EFFICIENT HANDLER FOR SMALL MAMMALS. PMID- 17735533 TI - THE INHIBITING EFFECT OF QUINONES ON THE GROWTH OF PENICILLIUM NOTATUM. PMID- 17735535 TI - The Role of Science in Our Unique Society. PMID- 17735536 TI - Lipodieresis in Liver Tissue of Depancreatized Dogs. PMID- 17735537 TI - Aspects of the Biologic Decay Periods of Sodium in Normal and Diseased Man. PMID- 17735538 TI - Isolation From Wild Bird Mites (Liponyssus sylviarum) of a Virus or Mixture of Viruses From Which St. Louis and Western Equine Encephalitis Viruses Have Been Obtained. PMID- 17735539 TI - Periconia circinata, the Cause of Milo Disease. PMID- 17735540 TI - Nature and Spatial Relationship of the Prosthetic Chemical Groups Required for Maximal Muscarinic Action. PMID- 17735541 TI - The Specific Heat of Human Blood. PMID- 17735543 TI - Proposed Method for Measuring the Movement of Soluble Fertilizer Salts in the Soil. PMID- 17735542 TI - Qualitative Reaction for 2,4-Dichlorophenoxyacetic Acid. PMID- 17735544 TI - COMMENT AND CRITICISM. PMID- 17735545 TI - THE CONDITIONAL LIBERATION OF PRISONERS. PMID- 17735546 TI - LONDON LETTER. PMID- 17735547 TI - HONOLULU LETTER. PMID- 17735548 TI - GEOGRAPHICAL NOTES. PMID- 17735549 TI - Inertia-force. PMID- 17735551 TI - Fish parasites in Meleagrinae. PMID- 17735550 TI - German constructions. PMID- 17735552 TI - A method of labelling museum specimens. PMID- 17735553 TI - An Ohio mound. PMID- 17735554 TI - Germ of hydrophobia. PMID- 17735555 TI - Youthfulness in science. PMID- 17735556 TI - National prosperity. PMID- 17735557 TI - THE ERUPTION OF KILAUEA. PMID- 17735558 TI - CLAY LAYERS IN NEW JERSEY AND THE ICE SHEET. PMID- 17735559 TI - MICROPHONES FOR THE PROTECTION OF BANK VAULTS. PMID- 17735560 TI - WOOD PRESERVATION. PMID- 17735561 TI - INDIAN MOUND OF OHIO. PMID- 17735563 TI - PUBLIC HEALTH PROGRESS AND RACE PROGRESS--ARE THEY INCOMPATIBLE? PMID- 17735562 TI - INVESTIGATIONS OF INFLUENZA IN ENGLAND. PMID- 17735565 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17735564 TI - DR. FRANKLIN P. MALL. PMID- 17735566 TI - MEAN SEA-LEVEL AS AFFECTED BY SHORELINE CHANGES. PMID- 17735567 TI - QUANTITATIVE DETERMINATION OF ROCK COLOR. PMID- 17735568 TI - A NEW FUNDAMENTALIST STRONGHOLD. PMID- 17735569 TI - THE INFLUENCE OF X-RAYS ON THE DEVELOPMENT OF DROSOPHILA LARVAE. PMID- 17735570 TI - THE ANTI-STERILITY VITAMIN E AND POULTRY. PMID- 17735571 TI - THE AMERICAN ASSOCIATION OF MUSEUMS. PMID- 17735572 TI - RECENT ADVANCES IN PHYSIOLOGICAL CHEMISTRY. PMID- 17735573 TI - ANCIENT GREEK FISH AND OTHER NAMES. PMID- 17735574 TI - ENGINEERING PROBLEMS IN A COURSE IN PHYSICS. PMID- 17735575 TI - ARGUMENTS ALLEGED AGAINST THE DOCTRINE OF ORGANIC EVOLUTION. PMID- 17735576 TI - EFFECT OF THE CONCENTRATION OF THE NUTRIENT SOLUTION UPON WHEAT CULTURES. PMID- 17735578 TI - RECENT WORK OF THE WISCONSIN ARCHEOLOGICAL SOCIETY. PMID- 17735577 TI - THE CLASSIFICATION OF THE ORDOVICIAN ROCKS OF OHIO AND INDIANA. PMID- 17735580 TI - NATIONAL PRESTIGE IN SCIENTIFIC ACHIEVEMENT. PMID- 17735579 TI - NATURE AND MAN. PMID- 17735581 TI - THE CRITERIA IN THE DECLARATION OF CHEMICAL INDEPENDENCE IN THE UNITED STATES. PMID- 17735583 TI - SYNTHESIS OF PALEONTOLOGY AND MEDICAL HISTORY. PMID- 17735582 TI - CHARLES RICHARD VAN HISE. PMID- 17735584 TI - A RECENTLY DISCOVERED ART CAVERN IN FRANCE. PMID- 17735586 TI - THE BALTIMORE MEETING OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17735585 TI - RHINEODON TYPUS, THE WHALE SHARK--FURTHER NOTES ON ITS HABITS AND DISTRIBUTION. PMID- 17735587 TI - Lake erie, not lake huron. PMID- 17735589 TI - Lake erie, not lake huron. PMID- 17735588 TI - Lake erie, not lake huron. PMID- 17735590 TI - The long wave. PMID- 17735591 TI - Mexican food system. PMID- 17735592 TI - Whither the price of oil? PMID- 17735593 TI - Fire mosaics in southern california and northern baja california. AB - In spite of suppression efforts, severe wildfires burn large areas of southern California grassland, coastal sage scrub, and chaparral. Such large burns may not have been characteristic prior to the initiation of fire suppression more than 70 years ago. To compare controlled with uncontrolled areas, wildfires of southern California and adjacent northern Baja California were evaluated for the period 1972 to 1980 from Landsat imagery. Fire size and location, vegetation, year, and season were recorded. It was found that suppression has divergent effects on different plant communities depending on successional processes, growth rates, fuel accumulation, decomposition rates, and length of flammability cycles. These variables establish feedback between the course of active fires, fire history, spatial configuration of flammable vegetation, and fire size. Suppression has minimal impact in coastal sage scrub and grassland. Fire control in chaparral reduces the number of fires, not burned hectarage; fires consequently increase in size, spread rate, and intensity and become uncontrollable in severe weather conditions. The Baja California chaparral fire regime may serve as a model for prescribed burning in southern California. PMID- 17735594 TI - Conditions for the successful use of science. AB - There is ground for concern that the British research and development effort, which is of considerable size, may not be well distributed. In some areas of intense scientific effort, commercial priorities tend to be forgotten. Too many of the units of the economic system are backward in understanding what science can offer and inefficient in using the opportunities which it provides. Evidence suggests that the successful use of science depends on the overall quality of management rather than specifically on its degree of scientific knowledge. PMID- 17735595 TI - NASA Gets a Fifth Orbiter Kit. PMID- 17735597 TI - Psychology Today in APA's Tomorrow. PMID- 17735596 TI - Soviets lag in key weapons technology. PMID- 17735598 TI - Gardner Appointed UC President. PMID- 17735599 TI - Minimizing the risk of contracting AIDS. PMID- 17735600 TI - Hit list at EPA? PMID- 17735601 TI - Waxman Bill Seen as Threat to NIH. PMID- 17735602 TI - Ophiolites: windows on which ocean crust? PMID- 17735603 TI - New magnets enhance synchrotron radiation. PMID- 17735604 TI - AAAS Annual Meeting Detroit, 26-31 May 1983 Tours. PMID- 17735605 TI - Tibet: accounts from china. PMID- 17735606 TI - Dasyurids and their kin. PMID- 17735607 TI - An era in classical physics. PMID- 17735609 TI - Grand unification. PMID- 17735608 TI - Biochemistry. PMID- 17735610 TI - Earthquake dating: an application of carbon-14 atom counting. AB - Milligram-sized specimens of detrital charcoal from soil layers associated with prehistoric earthquakes on the Wasatch fault in Utah have been dated by direct atom counting of carbon-14 with a tandem Van de Graaff accelerator. The measured ratios of carbon-14 to carbon-12 correspond to ages of 7800, 8800, and 9000 years with uncertainties of +/- 600 years. PMID- 17735611 TI - East Pacific Rise Near 13{degrees}N: Geology of New Hydrothermal Fields. AB - Abundant massive sulfide deposits are present at the crest of the East Pacific Rise near 13 degrees North, where the opening rate is about 12 centimeters per year. Large manganese and helium-3 anomalies in seawater samples, evidence of intense present-day activity of hydrothermal springs, indicate that sulfides are still being produced along this segment of the rise. Massive sulfides also occur on adjacent off-axis seamounts. PMID- 17735612 TI - Controlled stimulation of magnetospheric electrons by radio waves: experimental model for lightning effects. AB - Magnetospheric electrons precipitated by ground-based coded very low frequency radio transmissions have been detected by rocket measurement of bremsstrahlung x rays, caused by impact of the electrons with the upper atmosphere. The direct correlations obtained between the very low frequency signals and the x-rays demonstrate the limits of sensitivity required and indicate that this remote sensing technique would be useful for future study of very low frequency effects induced by single lightning strokes. PMID- 17735613 TI - Spider populations: extraordinarily high densities on islands without top predators. AB - Distributions and densities of orb spiders on small islands are extremely variable. Species occurrences are far more irregular for spiders than vertebrates on the same islands. Much variation in spider density is explainable by distance from the presumed source of colonists and presence or absence of vertebrate predators. As has been predicted for passive dispersers, densities decline exponentially with distance. For a given distance, spider densities are about ten times greater on islands without vertebrate predators than on those with such predators. PMID- 17735614 TI - THE UTILIZATION OF PATENTS FOR THE PROMOTION OF RESEARCH. PMID- 17735615 TI - ISOLATION CULTURES WITH SMALL AQUARIA. PMID- 17735616 TI - THE AURORA BOREALIS. PMID- 17735617 TI - TWO METHODS OF ORIENTATION OF SMALL OBJECTS IN PARAFFIN. PMID- 17735618 TI - APHIS IMMUNITY OF TEOSINTE-CORN HYBRIDS. PMID- 17735619 TI - THE TILLERING OF WHEAT. PMID- 17735621 TI - COMMENT AND CRITICISM. PMID- 17735620 TI - A MEANS OF TRANSMITTING THE FOWL NEMATODE, HETERAKIS PAPILLOSA BLOCH. PMID- 17735622 TI - THE INDIANA EARTHQUAKE. PMID- 17735623 TI - CIRCULATION OF THE SEA THROUGH NEW YORK HARBOR. PMID- 17735624 TI - THE RECENT ERUPTION OF MAUNA LOA. PMID- 17735625 TI - THE RIVIERA EARTHQUAKE. PMID- 17735626 TI - LONDON LETTER. PMID- 17735627 TI - GEOGRAPHICAL NOTES. PMID- 17735628 TI - On certain electrical phenomena. PMID- 17735629 TI - CHEMICAL STRUCTURE OF CYTOPLASM. PMID- 17735630 TI - WARTIME MAINTENANCE OF SCIENTIFIC PRODUCTION. PMID- 17735631 TI - ROSS AIKEN GORTNER 1885-1942. PMID- 17735632 TI - THE JAMES F. LINCOLN ARC WELDING FOUNDATION. PMID- 17735633 TI - BIOLOGICAL ABSTRACTS. PMID- 17735634 TI - THE CONSERVATION OF FISHERIES IN THE GREAT LAKES. PMID- 17735636 TI - HTE NATIONAL CHEMICAL EXPOSITION. PMID- 17735635 TI - THE AMERICAN MATHEMATICAL SOCIETY. PMID- 17735637 TI - TROPICAL MEDICINE AT TULANE UNIVERSITY. PMID- 17735638 TI - DEFORMATION OF ROCK STRATA BY EXPLOSIONS. PMID- 17735639 TI - AN ENDORSEMENT OF THE USE OF GENERIC NAMES AS COMMON NOUNS. PMID- 17735640 TI - THE NON-UTILIZATION OF LACTIC ACID BY THE LACTATING MAMMARY GLAND. PMID- 17735642 TI - PIMELIC ACID, BIOTIN AND CERTAIN FUNGI. PMID- 17735641 TI - THE AMERICAN ASSOCIATION OF VARIABLE STAR OBSERVERS. PMID- 17735643 TI - THE RH FACTOR AND RACIAL ORIGINS. PMID- 17735645 TI - AN ELECTRIC RECORDING MARKING COUNTER FOR THE CONSECUTIVE COUNTING OF SMALL OBJECTS. PMID- 17735644 TI - VITAMIN A AND THE THYROID. PMID- 17735646 TI - CONTROL OF BLUE MOLD OF TOBACCO BY A NEW SPRAY. PMID- 17735647 TI - Interference with radio astronomy. PMID- 17735648 TI - The argo merchant oil spill. PMID- 17735649 TI - A coming battle? PMID- 17735650 TI - Mass vaccination: probability of three sudden deaths. PMID- 17735651 TI - Alleviating confusion. PMID- 17735652 TI - Science: too much accountability. PMID- 17735653 TI - Paleogeographic reconstructions of coastal aegean archaeological sites. AB - Many studies have been made of ancient Greek topography, some of the more recent ones based on modern techniques. However, most still ignore the subsurface dimension of coastal and other environments and hence fail to fully explain coastal and alluvial-colluvial processes, rates of change of geomorphology, and the effects of coastal change on humans. In this article subsurface geological analyses have been used to elucidate paleogeographic coastal settings of major archaeological sites around the Aegean Sea. Similar approaches could be applied in the Middle and Far East and elsewhere in the Mediterranean. PMID- 17735655 TI - Breeder and other long-term energy projects cut back. PMID- 17735654 TI - Prospects for district heating in the United States. AB - Large-scale district heating, using waste heat rejected by electric power plants and other sources, is presented as a means of reducing significantly the amount of fossil fuel consumed for residential and commercial space and water heating in the United States. Analysis of the technical and economic aspects of model district heating systems for nine U.S. urban areas shows that district heat service to residential and commercial consumers would be economically attractive. Projections of national service levels show that up to half of the U.S. population could be served by district heating at costs that are competitive with the present costs of imported oil and also with projected costs of new energy forms. An advantage of district heat over the latter is that it is a proved, simple technology. PMID- 17735656 TI - Carter's Budget: Little Biomedical Growth; Energy Conservation Pushed. PMID- 17735657 TI - Science in europe/nuclear wastes stymie west germans. PMID- 17735658 TI - AAAS Meeting: Drought Was the Topic of the Week. PMID- 17735659 TI - Dispute over Jensen Election as Fellow Flares in Council. PMID- 17735661 TI - Carter on agricultural research. PMID- 17735660 TI - Brzezinski: role of science in society and foreign policy. PMID- 17735662 TI - Science advisers helped avert use of "nukes" in Vietnam. PMID- 17735663 TI - Hopes for the airbag on the rise. PMID- 17735665 TI - New Tests for Diagnosis of MS. PMID- 17735664 TI - The EAE Model: A Tentative Connection to Multiple Sclerosis. PMID- 17735667 TI - Regulation of cell growth. PMID- 17735666 TI - The breeder: French prototype shut down for repairs. PMID- 17735668 TI - Oswald T. Avery. PMID- 17735669 TI - Atomic physics. PMID- 17735670 TI - Myrmecology. PMID- 17735671 TI - Lunar soil: iron and titanium bands in the glass fraction. AB - A study of absorption bands in simulated lunar glasses resulted in the discovery of a Ti(4+)-O(2-) charge transfer band at 0.26 micrometer and two Fe(2+)-Ti(4+) bands at 0.34 and 0.42 micrometer. These results indicate that the properties of lunar soil are somewhat affected by the glass content but are controlled by other factors. PMID- 17735672 TI - Sulfate aerosol: its geographical extent in the midwestern and southern United States. AB - Sulfate particles (sulfuric acid and its neutralization products with ammonia) dominate the submicrometer-sized, light-scattering component of the aerosol in more than 90 percent of 2850 pairs of humidographic measurements made over a 3 month period at three rural midwestern and southern sites. The nearly continuous optical dominance by sulfate in the aerosol at these spatially varied locations, particularly in the Ozark Mountains, suggests that sulfate is a component of the submicrometer-sized aerosol that is distributed over a large geographical region and is not due to local sources. PMID- 17735673 TI - A cheetah-like cat in the north american pleistocene. AB - The discovery of abundant skeletal remains of Felis trumani from a late Pleistocene deposit in Wyoming shows that it was as highly modified for cursorial locomotion as the cheetah (Acinonyx). Several other Pleistocene felids that have been regarded as pumas seem to be related forms. The late Pleistocene fauna of the Big Horn Basin in Wyoming is dominated by cursorial taxa. PMID- 17735674 TI - First occurrence of the garnet-ilmenite transition in silicates. AB - Pyrope garnet (Mg(3)Al(2)Si(3)O(12)) has been found to transform to an ilmenite type phase at a loading pressure between 240 and 250 kilobars and at about 1000 degrees to 1400 degrees C in a diamond-anvil press coupled with laser heating. The lattice parameters for the ilmenite-type phase of (Mg(.75) Al(.25))(Si(.75) Al(.25))O(3) are a(0) = 4.755 +/- 0.002 and c(0) = 13.360 +/- 0.005 angstroms. The zero-pressure volume change associated with the garnet-ilmenite transition is calculated to be -7.1 percent. This result verifies the prediction that pyrope garnet would transform to the ilmenite structure at high pressure first suggested in 1962 by Clark et al. and Ringwood. PMID- 17735675 TI - Gordon research conferences. PMID- 17735677 TI - PRODUCTS and MATERIALS. PMID- 17735676 TI - Program summary, gordon research conferences 1977 schedule--new hampshire and california. PMID- 17735678 TI - Carter's Engineering Background. PMID- 17735679 TI - Carter's Engineering Background. PMID- 17735680 TI - Carter's Engineering Background. PMID- 17735681 TI - The science court. PMID- 17735682 TI - Clean air litigation. PMID- 17735683 TI - Clean air litigation. PMID- 17735685 TI - Astronomy, architecture, and adaptation at pueblo bonito. PMID- 17735684 TI - Universities and national research policy. PMID- 17735686 TI - Squall in chesapeake: marine institute rammed by junk charge. PMID- 17735687 TI - Laetrile: "quack" cancer remedy still brings hope to sufferers. PMID- 17735688 TI - Smithsonian insect zoo: a murmurous microcosm does its thing on the wing. PMID- 17735689 TI - NSF: Kennedy Pours Trouble on Oiled Waters. PMID- 17735690 TI - Erratum. AB - In the report "Aflatoxin production by a variant of Apergillus oryzae (NRRL strain 1988) on cowpeas (Vigna sinensis)" by N. El-Hag and R. E. Morse [192, 1345 (1976)], the third sentence in the legend to Table 1 should read "This strain produced aflatoxin on rice (expressed as micrograms per kilogram ...)." Also, the heading for columns 2 and 3 of Table 1 should read "Aflatoxin (microg/kg) from A. oryzae." PMID- 17735691 TI - Animal behavior: the puzzle of flavor aversion. PMID- 17735692 TI - Latest new particle caps the evidence for charm. PMID- 17735694 TI - Phylogenetic topics in ethology. PMID- 17735693 TI - Instructions for contributors. PMID- 17735695 TI - Actions of drugs. PMID- 17735696 TI - Biological membranes. PMID- 17735697 TI - Physics of instabilities. PMID- 17735698 TI - Particle physics. PMID- 17735699 TI - Earth rotation measured by lunar laser ranging. AB - The estimated median accuracy of 194 single-day determinations of the earth's angular position in space is 0.7 millisecond (0.01 arc second). Comparison with classical astronomical results gives agreement to about the expected 2 millisecond uncertainty of the 5-day averages obtained by the Bureau International de l'Heure. Little evidence for very rapid variations in the earth's rotation is present in the data. PMID- 17735700 TI - Cloud condensation nuclei on the atlantic seaboard of the United States. AB - Concentrations of cloud condensation nuclei measured along the East Coast from Virginia to Long Island ranged from 1000 to 3500 per cubic centimeter as compared to 100 per cubic centimeter in clean maritime air and 300 per cubic centimeter in continental air. The global anthropogenic production rate of cloud condensation nuclei may be comparable to the natural production rate; in some industrial areas cloud condensation nuclei are dominated by anthropogenic sources. PMID- 17735701 TI - Light flashes observed on skylab 4: the role of nuclear stars. AB - The astronauts on Skylab 4 observed bursts of intense visual light flash activity when their spacecraft passed through the South Atlantic Anomaly. Flash rates as high as 20 per minute have in the past been considered unexpectedly high. When the effect of nuclear interactions in and near the retina is included, the apparent anomaly is removed. PMID- 17735702 TI - Nitrogen Fixation in Grasses Inoculated with Spirillum lipoferum. AB - Field-grown pearl millet (Pennisetum americanum) and guinea grass (Panicum maximum), lightly fertilized and inoculated with Spirillum lipoferum, produced significantly higher yields of dry matter than did uninoculated controls. Up to 42 and 39 kilograms of nitrogen per hectare were replaced by inoculation for pearl millet and guinea grass, respectively. The data demonstrate that nitrogen fixation by these grass-Spirillum systems is efficient and is achieved at a reasonable energy cost to the plant. PMID- 17735703 TI - Acoustic tracking of ocean-dumped sewage sludge. AB - With a modified 200-kilohertz acoustic echo sounder, it has been possible to detect and map sewage dumped into the ocean over several hours. The three dimensional distribution of suspended material and its rate of diffusion are indicated after digital processing of the data. PMID- 17735704 TI - Island biogeography and conservation: strategy and limitations. PMID- 17735705 TI - PRODUCTS and MATERIALS. PMID- 17735706 TI - BIOLOGY AND WAR. PMID- 17735707 TI - ASYMMETRIC SYNTHESES AND THEIR BEARING ON THE DOCTRINE OF VITALISM. II. PMID- 17735708 TI - NEGATIVE SURFACE TENSION. PMID- 17735710 TI - PAMPHLET COLLECTIONS. PMID- 17735709 TI - INDUSTRIAL LABORATORIES AND SCIENTIFIC INFORMATION. PMID- 17735711 TI - THE WHITE PINE BLISTER RUST; DOES THE FUNGUS WINTER ON THE CURRANT? PMID- 17735713 TI - NOTES ON METEOROLOGY AND CLIMATOLOGY. PMID- 17735712 TI - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES. PMID- 17735714 TI - THE AMERICAN MATHEMATICAL SOCIETY. PMID- 17735715 TI - THE ROOT-ROT DISEASE OF THE APPLE IN VIRGINIA. PMID- 17735716 TI - THE AMERICAN GENETIC ASSOCIATION. PMID- 17735717 TI - AAAS Radiation Session. PMID- 17735719 TI - Soviet nuclear capabilities. PMID- 17735718 TI - "Ghost dumps". PMID- 17735720 TI - Corrections. AB - In the Research News article "New theory of hormones proposed" (12 Mar., p. 1383) by Gina Kolata, glycyrrhetinic acid and tetrahydrocannabinol were incorrectly identified as alkaloids. This misidentification in no way changes the conclusions about these plant substances. PMID- 17735721 TI - Omitted reference. PMID- 17735722 TI - Columbia journalism review: editorial policy. PMID- 17735723 TI - National engineering action conference. PMID- 17735724 TI - The Sun's Influence on the Earh's Atmosphere and Interplanetary Space. AB - The bulk of the sun's radiation is in the visible and infrared. Solar radiation at these wavelengths controls the weather in the lowest levels of the earth's atmosphere. The rate at which this energy is emitted (the so-called solar constant) varies by a few tenths of 1 percent over a time scale of days. Longer period variations may exist, but have yet to be detected. Far more variable are the amounts of energy emitted as ultraviolet, extreme ultraviolet, and x-rays, and in the continuous outflow of ionized solar particles. The latter controls the properties of the space between the earth and the sun as well as those of the earth's magnetosphere. The ultraviolet and particle emissions control the properties of the earth's upper atmosphere, including the global wind circulation and changes therein associated with intense auroral storms. While considerable progress has been made in exploring the solar-terrestrial system since the advent of space research, many problems remain. These include the question of how magnetic energy is converted into ionized particle energy in the sun and in the earth's magnetosphere, the way in which solar and terrestrial magnetic fields join or merge, and how large electric fields are generated and sustained a few thousand kilometers above the earth's poles. Perhaps the most intriguing question concerns the possible relation between solar variability and the earth's weather and climate. PMID- 17735725 TI - Steel recycling and energy conservation. AB - The potential for energy conservation through increased use of steel scrap by the U.S. steel industry is examined. It is concluded that increased use of scrap would reduce energy use, but it is not economical, due mainly to volatile scrap prices. Other energy-saving technologies exist, but it is likely that energy will be conserved through reduced use of steel as rising energy costs are passed through to consumers. PMID- 17735726 TI - Carter's Plan for MX Lives On. AB - Early this year, the U.S. land-based force of nuclear missiles became vulnerable on paper-to destruction in a preemptive attack by the Soviet Union. The Air Force has worried about this problem for a long time, searching high and low for a better place to put both the existing, silo-based Minuteman missiles and a new missile, the MX. Under the Carter Admnistration, the Air Force agreed to a missle basing plan known as MPS, for multiple protective shelters. The Reagan Administration has ostensibly dropped this plan in favour of several alternatives. Previous articles in this series explored why U.S. officials became alarmed about missile vulnerability; the genesis of a short-term plan to put more missiles into silos; continuing Air Force opposition to a plan for missiles on constantly roving aricraft; and a bizare plan to bury missiles deep underground. PMID- 17735727 TI - A legacy of technical problems. PMID- 17735728 TI - The politics of lead. PMID- 17735730 TI - Trial Set for Louisiana's Creationist Law. PMID- 17735729 TI - NRC Reports on Ginna Nuclear Plant Accident. PMID- 17735731 TI - GAO Ignores Flaw in Concept of Space War. PMID- 17735732 TI - Scrap NSF, Slash NIH, Conservatives Urge. PMID- 17735733 TI - Portraits of a parasite. PMID- 17735734 TI - Perfect shuffles and their relation to math. PMID- 17735736 TI - Intertidal ecology. PMID- 17735735 TI - Scientific data and public policy. PMID- 17735737 TI - An excitatory amino Acid. PMID- 17735738 TI - Movement of animals. PMID- 17735739 TI - Radionuclides in mono lake, california. AB - Several radioisotopes of the naturally occurring uranium and thorium decay series, in addition to fallout plutonium, have unusually high concentrations in the water column of Mono Lake, a natural alkaline, saline lake. Complexing by carbonate ions appears to be responsible for the enhanced solubility of actinide elements with oxidation states of IV to VI. In contrast, fallout strontium-90 has been largely removed from the water, probably as a result of coprecipitation with calcium carbonate. The daughter/parent activity ratios of thorium, radium, and uranium isotopes suggest that thorium is removed from the water column to the sediments on time scales substantially longer than a month and that the desorption of thorium from the sediments to the water column requires less than a few years. PMID- 17735740 TI - Elevated concentrations of actinides in mono lake. AB - Tetravalent thorium, pentavalent protactinium, hexavalent uranium, and plutonium (oxidation state uncertain) are present in much higher concentrations in Mono Lake, a saline, alkaline lake in eastern central California, than in seawater. Low ratios of actinium to protactinium and of americium to plutonium indicate that the concentrations of trivalent actinides are not similarly enhanced. The elevated concentrations of the ordinarily very insoluble actinides are maintained in solution by natural ligands, which inhibit their chemical removal from the water column, rather than by an unusually large rate of supply. PMID- 17735741 TI - Deep advective transport of lithogenic particles in panama basin. AB - Sediment traps were deployed at several depths between 660 and 3800 meters in the Panama Basin. The flux of lithogenic particles increased with increasing depth. This increase was due primarily to particles of beidellite (a smectite clay), which was identical to the clay occurring in bottom sediment on the continental slope to the west of the sediment trap mooring. The beidellite vertical flux at the Panama Basin station increased when an easterly current prevailed and decreased when the current reversed, indicating that a major portion of smectite was transported horizontally at mid-water depth to the mooring site from the nearby continental slope. PMID- 17735742 TI - Accumulation of airborne polychlorinated biphenyls in foliage. AB - Plant foliage accumulates the vapor of polychlorinated biphenyls (PCB's) from the atmosphere, and there is a variation in the amount that is accumulated from one plant species to another. This differential accumulation factor between species remains constant over more than two orders of magnitude of PCB concentrations in plants. The relationships between foliar and atmospheric PCB concentrations hold promise for cost-effective atmospheric PCB monitoring through foliar analyses. PMID- 17735743 TI - Current speed and filtration rate link caddisfly phylogeny and distributional patterns on a stream gradient. AB - Patterns of body size and net construction suggest that current speed and food particle concentration (not size) influence the distribution of suspension feeding caddisflies on a downstream gradient. Large ancestral taxa with high filtration rates occur in resource-poor upstream habitats; more derived members of the phylogeny enter successively in downstream reaches with slower current and greater concentrations of particulate food. PMID- 17735744 TI - Transfer of fermentative microbes between generations in a herbivorous lizard. AB - Iguana iguana is herbivorous throughout life and utilizes a microbial fermentation system in the elaborated hindgut to break down plant cell walls. Iguanas reared in captivity grew more slowly than wild hatchlings and failed to develop the same complex populations of fermentative microbes. Captive hatchlings fed fresh fecal material from an adult iguana acquired the complex microflora and grew as rapidly as wild hatchlings. In the field, hatchlings actively associated with adults during the first weeks of life and obtained the complex microflora during this time. Acquisition of the fermentative microflora by neonatal iguanas apparently requires direct contact with older conspecifics. PMID- 17735745 TI - SCIENCE AND SOCIETY. PMID- 17735746 TI - THE BUILDING OF THE NATIONAL ACADEMY OF SCIENCES. PMID- 17735747 TI - CHARLES NEWTON LITTLE. PMID- 17735749 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17735748 TI - THE SIGNIFICANCE OF THE "FOLLAR RAY". PMID- 17735750 TI - A CASE OF SUPERSENSITIVENESS TO THE POISONOUS ACTION OF THE CASTOR BEAN. PMID- 17735751 TI - FEMORAL DEFORMATION. PMID- 17735752 TI - A REMARKABLE DEVELOPMENT OF THE SPOROPHYTE IN ANTHOCEROS. PMID- 17735753 TI - THE EFFECT OF THE REMOVAL OF THE MICRONUCLEUS. PMID- 17735754 TI - THE AMERICAN CHEMICAL SOCIETY. PMID- 17735755 TI - THE STATE MUSEUM AND STATE PROGRESS. PMID- 17735756 TI - ADDRESS OF PRESIDENT TAFT AT THE FIFTEENTH INTERNATIONAL CONGRESS ON HYGIENE AND DEMOGRAPHY. PMID- 17735757 TI - TWELFTH ANNUAL INTERCOLLEGIATE EXCURSION OF NEW ENGLAND. PMID- 17735758 TI - THE STUDY OF MALARIA. PMID- 17735760 TI - THE ESKIMOS OF CORONATION GULF. PMID- 17735759 TI - RETIREMENT OF PROFESSOR HENRY SHALER WILLIAMS. PMID- 17735761 TI - GYROCOCCUS FLACCIDIFEX AND THE "FLACHERIE". PMID- 17735763 TI - A CLASSIFICATION OF THE DEPARTMENTS OF BOTANY AND AN ARRANGEMENT OF MATERIAL BASED THEREON. PMID- 17735762 TI - A NEW FLY TRAP. PMID- 17735764 TI - THE NEW CATALOGUE OF CHIROPTERA IN THE BRITISH MUSEUM. PMID- 17735765 TI - THE PRODUCTION OF SPERM ISO-AGGLUTININS BY OVA. PMID- 17735766 TI - PRELIMINARY NOTE ON PRISTINA AND NAIDIUM. PMID- 17735767 TI - CONCURRENT INFECTION BY FIVE SPECIES OF INTESTINAL WORMS, INCLUDING SCHISTOSOMA MANSONI. PMID- 17735768 TI - SCIENCE NEWS. PMID- 17735769 TI - THE PIONEERING PROCESS. PMID- 17735770 TI - RELATIONS OF BIOCLIMATICS TO THE OTHER SCIENCES. PMID- 17735772 TI - PERIGLACIAL PHENOMENA IN THE PUGET SOUND REGION. PMID- 17735771 TI - METER IN COMPOSITION. PMID- 17735773 TI - DURABLE FILMS. PMID- 17735774 TI - ACADEMIC FREEDOM IN SPAIN. PMID- 17735775 TI - THE DEFLECTION OF LIGHT IN THE SUN'S GRAVITATIONAL FIELD. PMID- 17735776 TI - NORMAL TISSUES AS A POSSIBLE SOURCE OF INHIBITOR FOR TUMORS. PMID- 17735778 TI - AIRPLANE OILING TO CONTROL MOSQUITOES. PMID- 17735777 TI - META-AMINO PARA-HYDROXY PHENYL ARSINE OXIDE AS AN ANTISYPHILITIC AGENT. PMID- 17735779 TI - PAPERS PRESENTED AT THE WASHINGTON MEETING. PMID- 17735780 TI - NATURAL HISTORY MUSEUMS (I). PMID- 17735781 TI - ANTHROPOLOGICAL EXHIBIT OF THE U. S. NATIONAL MUSEUM AT THE OMAHA EXPOSITION. PMID- 17735782 TI - CURRENT NOTES ON PHYSIOGRAPHY. PMID- 17735783 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17735784 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17735785 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17735786 TI - BIBLIOGRAPHICAL DATA FOR THE TITLE-PAGES OF BOOKS. PMID- 17735788 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17735789 TI - SCIENTIFIC JOURNALS. PMID- 17735787 TI - PROFESSOR KOCH ON MALARIA. PMID- 17735790 TI - Why Science Loses Students. PMID- 17735791 TI - Cover Recognition: A Parlor Game for Scientists. PMID- 17735792 TI - Bias in Standardized Tests. PMID- 17735794 TI - Intrauterine Ring. PMID- 17735793 TI - New Textbooks on Old Subjects. PMID- 17735795 TI - Timing Calls for Papers. PMID- 17735796 TI - Money, Accounting, and Research Talent. PMID- 17735797 TI - AAAS Space Poll. PMID- 17735798 TI - Modification Experiments on Tropical Cumulus Clouds: "Exploding" cumulus clouds by silver iodide seeding is used as a controlled experiment on their dynamics. PMID- 17735799 TI - Peter J. W. Debye: An Interview. AB - On 24 March Peter J. W. Debye, emeritus professor at Cornell University, began his 7th decade of active research in chemical physics and celebrated his 80th birthday. In anticipation of this occasion, three members of the Cornell staff Dale R. Corson, provost, former dean of the school of engineering, and, before that, professor of physics and chairman of the department; Edwin E. Salpeter, professor of theoretical physics; and S. H. Bauer, professor of chemistry interviewed Professor Debye on 5 March. This article consists of questions and answers selected from the tape recording of the interview. PMID- 17735800 TI - Foundations: Patman Maintains Pressure for Tighter Regulation of Tax-Exempt Organizations. PMID- 17735801 TI - Scientists in Politics: Council Founded by Szilard Brings Cash and Sophistication to Lobbying. PMID- 17735802 TI - Ranger VII: Briefing for Johnson Brings Out High Level Chit Chat on Various Aspects of Space. PMID- 17735803 TI - X-ray Diffraction Studies on Dysprosium at High Pressures. AB - Dysprosium has been studied at pressures up to about 160 kilobars, well above the transition reported near 50 kilobars by other workers. It shows no definite structural alteration from hexagonal close-packed structure throughout this range. It is suggested that the 50-kilobar transition is most likely electronic or magnetic in nature, or that the metal undergoes a hexagonal stacking rearrangement. PMID- 17735804 TI - High Pressure: Effect on Dysprosium. AB - The electrical resistance of dysprosium was studied in the temperature-pressure range 77 degrees to 200 degrees K and 15 to 120 kb. The variations of the Neel transition with pressure was found to good accuracy, the value of dT(N)/dP being 0.62+/-0.4 deg/kb. From this result, second-order thermodynamic equations yield values of -64 x 10-6 ( degrees C)(-1) and 4.0 x 10(-14) cm(2)/dyne for the changes in the coefficient of linear expansion and the compressibility, respectively, at the 1-atm Neel point. The Neel transition disappears at 45 to 55 kb, and no magnetic transitions are seen at higher pressures in the temperature range indicated. The other boundaries in the region investigated have been determined but are very uncertain. The cause of the cusp in the isothermal compressions is not clear from the available data. Above the Neel boundary, the pressure dependence of the cusp with respect to temperature, dP/dT, is very small and may even be zero. Below the Neel temperature, dP/dT is uncertain. From isothermal measurements, the value is -1, while from the isobaric measurements a value of -0.25 is obtained. PMID- 17735805 TI - Recent High Relative Sea Level Stand near Recife, Brazil. AB - Radiocarbon dates for Vermetidae limestone from the edge of the Brazilian Shield at Cape San Agostinho, Brazil, indicate sea level stands of up to 2.60 meters above the present position, 3660, 2790, and 1190 years ago. Accurate determination of relative sea level is possible because of the well-defined habitat of the fossils dated. PMID- 17735806 TI - Superconducting Metastable Compounds. AB - A number of metastable phases, germanides and tellurides of gold and silver, have been prepared, analyzed by x-ray diffraction, and investigated for superconductivity. The new superconductors and their transition temperatures are AgTe(3) (2.6 degrees K), Ag(4)Ge (0.85 degrees K), Au(3)Te(5) (1.62 degrees K), and Au(1-x)Ge(x) (0.99 degrees K-1.63 degrees K) where (0.27 R-Cl+Cu(I)Cl(n-1) can also be described. Hopefully, these simple redox mechanisms will be utilized in rationalizing complex reactions and formulating new syntheses. The limited number of examples cited in this short review represent only an introduction to the vast area of chemical research to be tapped in the study of the mechanisms and the synthetic utility of oxidation reduction reactions and catalysis. PMID- 17737551 TI - Nutrient cycling. AB - The small-watershed approach to problems of nutrient cycling has these advantages. (i) The small watershed is a natural unit of suitable size for intensive study of nutrient cycling at the ecosystem level. (ii) It provides a means of reducing to a minimum, or virtually eliminating, the effect of the difficult-to-measure variables of geologic input and nutrient losses in deep seepage. Control of these variables makes possible accurate measurement of nutrient input and output (erosion) and therefore establishes the relationship of the smaller ecosystem to the larger biospheric cycles. (iii) The small-watershed approach provides a method whereby such important parameters as nutrient release from minerals (weathering) and annual nutrient budgets may be calculated. (iv) It provides a means of studying the interrelationships between the biota and the hydrologic cycle, various nutrient cycles, and energy flow in a single system. (v) Finally, with the small-watershed system we can test the effect of various land-management practices or environmental pollutants on nutrient cycling in natural systems. PMID- 17737552 TI - Where is biology taking us? PMID- 17737553 TI - LBJ's Budget: Lean Fare Set Forth for Research and Development. PMID- 17737554 TI - CERN: Regional Cooperation Amid Tightening Budgets. PMID- 17737555 TI - Test detection: decoupling theory verified, but does it matter? PMID- 17737557 TI - Treatise on diatoms. AB - In R. E. Norris's review of The Diatoms of the United States Exclusive of Alaska and Hawaii, volume 1, by Ruth Patrick and Charles; W. Reimer [153, 1369 (16 Sept. 1966)], the Introduction, which was signed only by Patrick, was erroneously attributed to Patrick and Reimer. PMID- 17737559 TI - Search for 21-Centimeter Radiation near Cosmic X-Ray Sources. AB - A search was made for 21-centimeter wavelength radiation in the regions of seven of the cosmic x-ray sources. No new sources with flux densities greater than 5.5 flux units were found. PMID- 17737560 TI - Lunar transient phenomena: topographical distribution. AB - The sites named in nearly 400 reports of lunar transient phenomena fall into three classes: (i) sites peripheral to the maria, (ii) ray craters, and (iii) ring plains with dark or partially dark floors; none are known in the rugged highland area of the southeast (International Astronomical Union, 1964; classically southwest) quadrant. Permanent records are few; the sites where known are consistent with the visual records. PMID- 17737558 TI - Aluminum-26 in pacific sediment: implications. AB - Aluminum-26 has been detected in a sample of sediment from the South Pacific. The disintegration rate of 0.8 disintegration per minute per kilogram of dry sediment is considerably higher than that expected from cosmic-ray spallation of atmospheric argon; it appears to result mainly from accretion of activity induced in interplanetary dust by solar-flare particles. This finding is in keeping with Wasson's published estimates regarding the magnitude of this effect, and confirms the order-of-magnitude correctness of the solar-particle flux and terrestrial accretion rate of interplanetary dust used in that calculation. PMID- 17737561 TI - Niningerite: a new meteoritic sulfide. AB - Niningerite, a new meteoritic sulfide ranging in composition from (Fe(0.19)Mg(0.66)Mn(0.14)Ca(0.007)Cr(0.002))S to (Fe(0.52)Mg(0.33)Mn(0.06)Ca(0.06)Cr(0.03)Zn(0.004))S, from the type-I enstatite chondrites Abee, Saint Sauveur, Adhi-Kot, Indarch, St. Mark's, and Kota-Kota, is described. It is named in honor of H. H. Nininger. PMID- 17737562 TI - Digital model of evaporite sedimentation. AB - A deterministic digital model to simulate evaporite sedimentation permits experimentation with depth of water, shape of salt basin, number, position, and strength of the inlets, and rate of evaporation. It provides a reasonable fit to salt thickness and distribution in the Upper Silurian Salina Formation of Michigan. PMID- 17737563 TI - Trial balloons in the southern hemisphere. AB - Superpressure GHOST balloons are being launched from Christchurch, New Zealand, to determine their life, stability, and clustering characteristics at several altitudes. Thtee separate balloons have flown for more than 6 months at 200 millibars, proving capability of the long life that had been hoped for at such middle altitudes and providing preliminary trajectory data for the Southern Hemisphere. Icing problems at lower altitudes have not yet been solved. We expect future flight durations of several years at higher altitudes. If successful, the new balloons will be useful platforms for experimenters concerned with study of large-scale and long-term effects in the stratosphere. PMID- 17737564 TI - Structure of silica glass. AB - From configurational entropy considerations, it is estimated that the grains in silica glass are far more likely to have a cristobalite structure than a pentagonal dodecahedral one. PMID- 17737565 TI - The Ecological Significance of Sexual Dimorphism in Size in the Lizard Anolis conspersus. AB - Adult males of Anolis conspersus capture prey of significantly larger size and occupy perches of significantly greater diameter and height than do adult females; similarly, these three dimensions of the niche are significantly larger for adult females than for juveniles. Adult males on the average eat a smaller number of prey, and the range in size of prey is larger. The relationship between the average length of the prey and that of the predator is linear when the predator size is above 36 millimeters, but becomes asymptotic when it is below that value. Subadult males as long as adult females eat significantly larger food than do the latter, but only in the larger lizards is this correlated with a relatively larger head. Anolis conspersus selects prey from a wide range of taxa and shows no obvious intraspecific specialization not connected to differences in microhabitat and prey size. The efficiency of this system for solitary species is pointed out. PMID- 17737566 TI - Seal ears. PMID- 17737568 TI - The Lost Legion. PMID- 17737567 TI - Chemical disinfection in industry, food, and agriculture. PMID- 17737571 TI - Drug Synergism. PMID- 17737569 TI - News of Science. PMID- 17737572 TI - Radioactive Wrist Watches. PMID- 17737574 TI - Equipment. PMID- 17737573 TI - Drug Synergism. PMID- 17737575 TI - Effort reporting and cost sharing of federal research. PMID- 17737576 TI - On scientific illiterature. PMID- 17737578 TI - That biblical spider: the end of the series. PMID- 17737577 TI - Don'T dam the grand canyon! PMID- 17737579 TI - Animal care legislation. PMID- 17737581 TI - Excretion and heartwood formation in living trees. PMID- 17737580 TI - Remarks on nuclear structure. PMID- 17737582 TI - Distribution of wild wheats and barley. AB - If we accept the evidence at face value, we are led to conclude that emmer was probably domesticated in the upper Jordan watershed and that einkorn was domesticated in southeast Turkey. Barley could have been domesticated almost anywhere within the arc bordering the fertile crescent. All three cereals may well have been harvested in the wild state throughout their regions of adaptation long before actual farming began. The primary habitats for barley, however, are not the same as those for the wheats. Wild barley is more xerophytic and extends farther downslope and into the steppes and deserts along the wadis. It seems likely that, while all three early cereals were domesticated within an are flanking the fertile crescent, each was domesticated in a different subregion of the zone. Lest anyone should be led to think the problem is solved, we wish to close with a caveat. Domestication may not have taken place where the wild cereals were most abundant. Why should anyone cultivate a cereal where natural stands are as dense as a cultivated field? If wild cereal grasses can be harvested in unlimited quantities, why should anyone bother to till the soil and plant the seed? We suspect that we shall find, when the full story is unfolded, that here and there harvesting of wild cereals lingered on long after some people had learned to farm, and that farming itself may have orig inated in areas adjacent to, rather than in, the regions of greatest abundance of wild cereals. We need far more specific information on the climate during incipient domestication and many more carefully conducted excavations of sites in the appropriate time range. The problem is far from solved, but some knowledge of the present distribution of the wild forms should be helpful. PMID- 17737583 TI - Victim-induced criminality. AB - In summary, there are certain issues that need to be dealt with if a coherent system of victim compensation is to be created. 1) Is the victim's entitlement to compensation qualified by his behavior in connection with the crime? If a Texas tycoon visits a clip joint, flashes a fat roll of bills, and gets hit on the head and rolled, is he entitled to compensation? If a man enters into a liaison with another's wife and gets shot by the husband, should his dependents be compensated? If a woman goes walking alone in a disreputable neighborhood and is assaulted, is she entitled to compensation? Unless the answer to such questions is a flat "yes," the adjudication of victim compensation as a "right" would be embarkation upon a vast sea of confusion. On the surface it may seem simpler to bypass the issue of "right" and declare for victim compensation as a matter of social policy-a logical extension of the welfare state approach. But the apparent simplicity may quickly prove illusory, in light of the second issue. 2) Is the victim's entitlement to compensation on the basis of indigency to be qualified by the requirement that an offender be apprehended and his guilt determined by a court? There are two levels to this problem. First, if a severely injured man reports to police that he has been mugged and robbed and if the police cannot apprehend a suspect, how is the administrator of compensation to know that the man is in fact the victim of a crime? The administrator of compensation must determine whether the episode was a criminal act or an argument-and who started it, and who precipitated the violence. What shall be the role of the witnesses, and of investigators? More important is the second level of the problem: How will law-enforcement of ficials and the courts evaluate the testimony of the victim if compensation of the victim may be at stake? In the evaluation of proposals for victim compensation, criminologists may need to think very hard about such questions and about the probable effects on the administration of criminal justice. These are pragmatic problems; there is a third problem which may at this time seem speculative, but is, nevertheless, quite important. 3) To what extent will a particular proposal for victim compensation contribute to a temptation opportunity pattern in victim behavior? In previous studies it has been pointed out that large numbers of our fellow Americans have tended to acquire casual money-handling habits-generically designated "carelessness"-which contribute to the national growth of criminality. How the victim helps the criminal was sketched in reports of those studies (10). It was made abundantly clear that human beings in our affluent society cannot be assumed to be prudent or self protective against the hazards of crime. Even when the "victim" is not overtly acting to commit a crime-as in the case of the property owner who hires an arsonist-he often tempts the offender. Among the victims of burglary statistically the most prevalent crime in the United States-are a substantial number of Americans who keep cash, jewelry, and other valuables carelessly at home or in hotel rooms to which the burglar has easy access through door or window. Victims of automobile theft-one of the fastest growing classes of crime include drivers who leave the vehicle or its contents invitingly accessible to thieves. And so on with other classes of crime. As pointed out in previous studies, when victim behavior follows a temptation-opportunity pattern, it (i) contributes to a "climate of criminal inducements," (ii) adds to the economic resources available to criminal societies, and (iii) detracts from the ability of lawenforcement agencies to suppress the growth of crime. PMID- 17737584 TI - Canada: science advisors to propose priorities. PMID- 17737585 TI - HUAC: Inquiry into Peace Movement Has Ramifications in Academia. PMID- 17737586 TI - Genetic relations of oceanic basalts as indicated by lead isotopes. AB - The isotopic compositions of lead and the concentrations lead, uranium, and thorium in samples of oceanic tholeiite and alkali suites are determined, and the genetic relations of the oceanic basalts are discussed. Lead of the oceanic tholeiites has a varying lead-206: lead-204 ratio between 17.8 and 18.8, while leads of the alkali basalt suites from Easter Island and Guadalupe Island are very radiogenic with lead-206: lead-204 ratios between 19.3 and 20.4 It is concluded that (i) the isotopic composition of lead in oceanic tholeiite suggests that the upper mantle source region of the tholeiite was differentiated from and original mantle material more than 1 billion years ago and that the upper mantle is not homogeneous at the present time, (ii) less than 20 million years was required for the crystal differentiation within the alkali suite from Easter Island, (iii) no crustal contamination was involved in the course of differentiation of rocks from Easter Island; however, some crustal contamination may have affected Guadalupe Island rocks, and (iv) alkali basalt may be produced from the tholeiite in the oceanic region by crystal differentiation. Alternatively the difference in the isotopic composition of lead in oceanic basalts may be produced by partial melting at different depths of a differentiated upper mantle. PMID- 17737587 TI - Lunar Orbiter: Tracking Data Indicate Properties of Moon's Gravitational Field. AB - After only a few days in orbit, the first U.S. satellite of the moon has already produced data which have provided new information about the moon's gravitational field. Results indicate that the spacecraft will probably not impact on the moon before it completes its photographic mission, but that it will probably do so in about 8 months. Preliminary indications are that the moon has a relatively large pear-shaped component and that the gravitational properties will be of considerable scientific interest. PMID- 17737588 TI - Oxygen fugacities directly measured in magmatic gases. AB - An electrochemical device was used to measure the fugacity of oxygen (fo(o2)) in holes drilled through the crust of Makaopuhi lava lake, Kilauea Volcano, Hawaii. Results obtained within 6 months of the lake formation show that log fo(o2) normally varies linearly with the reciprocal of the absolute temperature, and that chemical changes occurring in the cooling tholeiitic basalt are reflected in the fo(o2) values measured in the holes. PMID- 17737589 TI - Marangoni flow: an additional mechanism in boiling heat transfer. AB - Experimental results indicate that extensive liquid circulation can be established by surface tension gradients near bubbles attached to heated surfaces. This circulation can contribute significantly to the high rate of heat transfer observed under boiling conditions. PMID- 17737590 TI - Brightness distributions of radio sources at 2-centimeter wavelength. AB - Maps have been made of the 2-centimeter brightness distribution of M17, Cassiopeia-A, Taurus-A, and Orion nebula with a resolution of 2.3 minutes of arc, revealing several newly resolved features. M17 is a double thermal source. Some structure appears in Cassiopeia-A, including a suggestion of a ring shape. Taurus A exhibits a brightness map similar to that obtained in earlier low-frequency results. The central part of Orion nebula is circularly symmetric to a high degree of accuracy. PMID- 17737591 TI - Tropopause detected by radar. AB - The tropopause has been detected by ultrasensitive, narrow-beam, microwave (10.7 centimeter) and ultrahigh-frequency (71.5-cm) radars. Its reflectivity is consistent with that expected theoretically for a refractively turbulent medium. Indications are that the layer is also mechanically turbulent, and that electromagnetic scatter techniques may be used to detect high-altitude clear-air turbulence. PMID- 17737592 TI - Mercury: infrared evidence for nonsynchronous rotation. AB - An infrared observation of the dark side of Mercury made by Pettit and Nicholson in 1923 led them to suggest that the planet rotates nonsynchronously. Their early measurements, if taken at face value, would imply a brightness temperature of about 180 degrees K for the dark side. The asymmetry of the infrared phase curve is further interpreted as suggesting direct rotation. PMID- 17737593 TI - Generation and Detection of Coherent Elastic Waves at 114,000 Mc/sec. AB - Coherent elastic waves were generated and detected at 114,000 megacycles per second in quartz at liquid-helium temperatures. Effective input power was approximately 3 milliwatts. The results suggest that the piezoelectric method may be applicable to similar experiments at much higher frequencies. PMID- 17737594 TI - Brassica campestris L.: Floral Induction by One Long Day. AB - A strain of Brassica campestris L. responds to a single photoinductive cycle 4 days after sowing. Extending the photoperiod from 8 to 22 or 24 hours, with incandescent light of 538-lux intensity, induced inflorescence in 90 percent of the plants. Inflorescence development was visible on dissection 5 or 6 days after photoinduction. Floral induction increased with duration and intensity of the supplementary light. PMID- 17737595 TI - Occurrence of isoprenoid Fatty acids in the green river shale. AB - The most abundant free fatty acids present in a sample of shale from the Green River Formation (Eocene, about 60 x 10(6) years) from Sulfur Creek are the acylic C(19) and C(20) isoprenoid acids. The dominance of these acids parallels the abundance of the corresponding hydrocarbons pristane and phytane. PMID- 17737596 TI - Anolis carolinensis: Effects of Feeding on Reaction to Aposematic Prey. AB - During a 15-day experiment, green anoles, Anolis carolinensis, were: (i) presented with one of two aposematic insects, Oncopeltus fasciatus or Photinus pyralis, during days 4, 6, and 8; (ii) maintained on one of four different food levels during days 9-14; and (iii) presented with the original model on day 15. Lizards on low rations tended to capture more Photinus on day 15 than did anoles on higher rations. No such correlation was observed with Oncopeltus. PMID- 17737597 TI - Bioluminescence. PMID- 17737598 TI - Forthcoming events. PMID- 17737599 TI - This week in science. PMID- 17737600 TI - Science in Japan: a status report. PMID- 17737601 TI - Erratum. AB - Results of a California state survey on ground water contamination were incorrectly reported in the article "Ground water ills: Many diagnoses, few remedies" by Marjorie Sun (News & Comment, 20 June, p. 1490). Six percent, not one-fifth, of California's large drinking water wells fed by ground water exceeded state pollution limits. One-fifth of the wells showed trace amounts of organic chemicals. PMID- 17737602 TI - Response: space shuttle development. PMID- 17737603 TI - Space shuttle development. PMID- 17737604 TI - School Reformers Aim at Creativity: Finding a "state of desolation" in the schools, Japanese leaders plan a sweeping revision of the educational system. PMID- 17737605 TI - Japan's U.S. R&D Role Widens, Begs Attention: Industry and university overtures, politics, and necessity have spurred Japan to enter into more American-based research. PMID- 17737606 TI - New Toyota--GM Plant Is U.S. Model for Japanese Management: Novel union contract allows for cooperation, not confrontation, in the "constant search for improvement". PMID- 17737607 TI - The Japanese infiltration. PMID- 17737608 TI - House backs translation of Japanese journals. PMID- 17737609 TI - Scientific american sale announced--then challenged. PMID- 17737610 TI - Justices kill key part of budget deficit act. PMID- 17737611 TI - British scientists urged to resist u.s. Controls on use of supercomputers. PMID- 17737612 TI - Now Four Laboratories Have Squeezed Light: But a group at the University of Texas at Austin, reporting a 42% reduction in the noise recorded by a detector, is the second-lap leader in the squeezing sweepstakes. PMID- 17737613 TI - Faster division with computers. PMID- 17737614 TI - Military statistics on AIDS in the u.s. PMID- 17737615 TI - Technological diversification of Japanese industry. AB - A Japanese database on research and development that disaggregates an industry's intramural expenditure into 31 different product fields is used tp measure technological diversification. Sectoral patterts are identified in terms of upstream, downstream, and horizontal diversification-that is, respectively, diversification of an industry's research and development activities into product fields that are industrial inputs of that industry, into those that are outputs, and diversification that is not directed through the path of input-output relations. The pattern of the electronics industry is identified as downstream diversification whereas that of the chemical industry is identified as horizontal. The declining industry is generally making upstream diversification. Japanese corporate and governmental policies, such as trade policy, industrial policy, and the research association scheme, have accelerated technological diversification. PMID- 17737616 TI - Japanese research and technology policy. AB - Until recently the Japanese did not spend much on research and what they did spend was concentrated on the commercial development of technology. As a result there have so far been few Japanese breakthroughs in either science or technology. Dramatic changes have recently occurred, however, and Japan now trails only the United States and the Soviet Union in research spending. Beyond this, Japanese policy-makers are making a determined effort to overcome Japan's social and institutional barriers to scientific creativity. PMID- 17737617 TI - Japanese competitiveness and Japanese management. AB - Japanese-style management and industrial policy are shown to serve as a source of industrial dynamism and are used as a way to illminate what is wrong with the American system. Japanese labor practices-specifically extra hours of unpaid work are seen as a form of insurance fee that the worker pays in exchange for job security. PMID- 17737618 TI - Organic synthesis in Japan: from natural products to synthetic control. AB - Organic chemistry in present day Japan, which has developed from early interest in natural products chemistry, now includes total synthesis, physical organic chemistry, synthetic methods, and organometallic chemistry. In this article, the current state of Japanese organic chemistry is briefly reviewed and a representative aspect of today's organic chemistry-exploration of new synthetic methodology-is discussed. PMID- 17737619 TI - Recent earthquake prediction research in Japan. AB - Japan has experienced many major earthquake disasters in the past. Early in this century research began that was aimed at predicting the occurrence of earthquakes, and in 1965 an earthquake prediction program was started as a national project. In 1978 a program for constant monitoring and assessment was formally inaugurated with the goal of forecasting the major earthquake that is expected to occur in the near future in the Tokai district of central Honshu Island. The issue of predicting the anticipated Tokai earthquake is discussed in this article as well as the results of research on major recent earthquakes in Japan-the Izu earthquakes (1978 and 1980) and the Japan Sea earthquake (1983). PMID- 17737620 TI - Brownian motion and nonequilibrium statistical mechanics. AB - This article is a personal reflection of the branch of nonequilibrium statistical mechanics called the linear response theory that has as its heart the fluctuation dissipation thereom, which states that irreversible processes ip nonequilibrium are necessarily related to thermal fluctuations in equilibrium. Its origi lies in the Einstein relation for the diffusion constant and the mobility of a Brownian particle. The short history of the fluctuation-dissipation theorem is described. Then the linear response theory is brifly summarized and the meaning of stochastization is considered. The Langevin equation approach and its extensions are reviewed. PMID- 17737621 TI - Evolution of meson science in Japan. AB - Forty years after Yukawa predicted the existence of mesons, experimental research activities with the use of mesons were started in Japan. Particles of the "second generation," which have nothing to do with the structure of ordinary materials, such as muons, K mesons, and other exotic particles have been exploited as unique probes to study new constituents of matter. PMID- 17737622 TI - Iridium abundances across the ordovician-silurian stratotype. AB - Chemostratigraphic analyses in the Ordovician-Silurian boundary stratotype section, bracketing a major extinction event in the graptolitic shale section at Dob's Linn, Scotland, show persistently high iridium concentrations of 0.050 to 0.250 parts per billion. There is no iridiumn concentration spike in the boundary interval or elsewhere in the 13 graptolite zones examined encompassing about 20 million years. Iridium correlated with chromium, both elements showing a gradual decrease with time into the middle part of the Lower Silurian. The chromium iridium ratio averages about 10(6). Paleogeographic and geologic reconstructions coupled with the occurrence of ophiolites and other deep crustal rocks in the source area suggest that the high iridium and chromium concentrations observed in the shales result from terrestrial erosion of exposed upper mantle ultramafic rocks rather than from a cataclysmic extraterrestrial event. PMID- 17737624 TI - Differential reflex activity determines claw and closer muscle asymmetry in developing lobsters. AB - The paired claws and closer muscles of the lobster, Homarus americanus, are identical in the early juvenile stages, but subsequently differentiate into a stout crusher claw with only slow fibers and a slender cutter with largely fast fibers. Rearing with different substrates or exercise of the claws revealed that claw laterality is determined in the central nervous system by differential reflex activity in the paired claws; the side with greater activity becomes the crusher, while the contralateral side becomes the cutter. PMID- 17737623 TI - Melittin-Like Peptides from the Shark-Repelling Defense Secretion of the Sole Pardachirus pavoninus. AB - Three ichthyotoxic peptides, pardaxins P-I to P-3, have been isolated from the defense secretion of the sole Pardachirus pavoninus. Pavoninins, the steroid glycosides with shark-repelling ability, had previously been isolated therefrom. Each pardaxin consists of 33 amino acid residues having a distinctly hydrophilic carboxyl terminal region and a predominantly hydrophobic remainder; the pardaxin is thus strongly surfactant. These peptides show marked physical and pharmacological similarities to melittin, the major active constituent of bee venom, yet they lack sequence homology. They are probably also responsible for the predator-repelling property of the sole. PMID- 17737626 TI - North american lakes: quaternary evolution of the great lakes. PMID- 17737625 TI - Temperature regulation of bacterial activity during the spring bloom in newfoundland coastal waters. AB - While the spring phytoplankton bloom in Newfoundland coastal waters is in progress during April and May, at water temperatures between -1 degrees and +2 degrees C, bacterial growth and respiratory rates remain low. Microbial community respiration is not measurable at -0.2 degrees C. Particulate materials that would be utilized by microorganisms in 2 to 3 days at 20 degrees to 25 degrees C require 11 days at 4 degrees C and 18 days at -0.2 degrees C. Thus, photosynthesis is active but microbial utilization of the products is suppressed. High secondary production in cold water may result from the low rate of microbial decomposition, enabling herbivores to utilize much of the primary production. PMID- 17737628 TI - Stellar development: birth and evolution of massive stars and stellar groups. PMID- 17737627 TI - An assessment of ethnology: a century of controversy. PMID- 17737629 TI - Space ventures in britain: history of british space science. PMID- 17737630 TI - Products & materials. PMID- 17737631 TI - HEREDITY AND ENVIRONIC FORCES. PMID- 17737632 TI - TENDENCIES IN PATHOLOGY. PMID- 17737634 TI - A BRITTLE-STAR NEW TO THE WOODS HOLE REGION. PMID- 17737633 TI - CHARLES A. YOUNG. PMID- 17737635 TI - THE FOUR INSEPARABLE FACTORS OF EVOLUTION. THEORY OF THEIR DISTINCT AND COMBINED ACTION IN THE TRANSFORMATION OF THE TITANOTHERES, AN EXTINCT FAMILY OF HOOFED ANIMALS IN THE ORDER PERISSODACTYLA. PMID- 17737636 TI - A LETTER RELATING TO THE BIOGRAPHY OF LAMARCK. PMID- 17737637 TI - EDWARD GARDINER GARDINER. PMID- 17737638 TI - PYORRHEA IN FOSSIL ANIMALS. PMID- 17737639 TI - PREVALENCE OF DIABETES. PMID- 17737640 TI - ISOTOPES OF OXYGEN. PMID- 17737641 TI - LEARNING BY ADULT RATS. PMID- 17737642 TI - INSECT RESPIRATION. PMID- 17737643 TI - HIDEYO NOGUCHI. PMID- 17737644 TI - THE IMPORTANCE OF NATURAL AREAS TO FORESTRY OFFICIALLY RECOGNIZED. PMID- 17737645 TI - THE NORTHERN LIGHTS OF JUNE 7, 1928. PMID- 17737647 TI - AUTOMOBILES AND ANIMAL MORTALITY. PMID- 17737646 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17737648 TI - INTERPRETING THE GRAND CANYON. PMID- 17737650 TI - SINANTHROPUS PEKINENSIS: THE RECOVERY OF FURTHER FOSSIL REMAINS OF THIS EARLY HOMINID FROM THE CHOU KOU TIEN DEPOSIT. PMID- 17737649 TI - A STANDARD MICROCINEMATOGRAPHIC APPARATUS. PMID- 17737651 TI - AN ULTRA-VIOLET LEAD OXIDE BAND SYSTEM. PMID- 17737653 TI - THIRTY-NINTH ANNUAL MEETING OF THE OHIO ACADEMY OF SCIENCE. PMID- 17737652 TI - THE LIFE-CYCLE OF HAPLOBOTHRIUM GLOBULIFORME COOPER 1914. PMID- 17737654 TI - This week in science. PMID- 17737655 TI - Soviet science and technology at the Boston meeting. PMID- 17737656 TI - Definition required. PMID- 17737657 TI - Response: paleolithic diet, evolution, and carcinogens. PMID- 17737658 TI - Response: liability insurance and litigation. PMID- 17737659 TI - Adapting to Pork-Barrel Science: Opponents of congressional earmarking of funds for academic projects shift strategy, but are finding that they face other issues of who gets what and how in science. PMID- 17737660 TI - A Matter of Time: Bowing to celestial time, the world's timekeepers will slow their atomic clocks with a "leap second" at the New Year. PMID- 17737661 TI - Soviets Pin Economic Hopes on Technology: Gorbachev's advisers outline drive to reshape the Soviet economy, upgrade education, and expand research. PMID- 17737662 TI - Europe in Space: The Program Is in French: Concern over the INF treaty's impact on Europe's security was one of several factors that helped forge last month's agreement between France and Germany on three new space programs. PMID- 17737663 TI - European southern observatory. PMID- 17737664 TI - Tower Study Hints at a "Sixth Force": Little is seen of the "fifth force" repulsion, but the researchers do see a new kind of gravitational attraction; if true, the results make gravity more complicated than ever. PMID- 17737665 TI - Superconductor's Critical Current at a New High: A new processing technique brings the copper oxide materials much closer to practical applications; meanwhile, there are controversial hints of superconductiivity at 500 K. PMID- 17737666 TI - A weakness in process technology. AB - Although the United States seems to be neither behind when it comes to research and development on new products or the willingness of its consumers to buy new products, the evidence clearly shows that it is behind when it comes to process technologies. Often Americans, even when a correction is made for wage differences, cannot produce goods at the price or quality levels achieved abroad. There is no one overriding reason for this lag in process technologies. An undereducated and trained labor force, too little savings and investment, a failure to see production as a central task, and a number of other factors have all contributed to the problem. PMID- 17737667 TI - Ceramics by the solution-sol-gel route. AB - The use of solution mixing followed by gelation to make ultrahomogeneous glasses and ceramics of various oxide compositions for laboratory experimentation, with first organic and later principally colloidal inorganic, precursors was developed over 30 years ago. Major technologies that use the solution-sol-gel route have been developed to make nuclear fuel pellets, ceramic fibers, thin coatings, and abrasive grain. This article reviews the early history and summarizes present research in this field, particularly new processes aimed at achieving xerogel precursors of maximum heterogeneity with respect either to composition or to structure. Such nanocomposites provide major advantages in lowering sintering temperatures, refining microstructure, and controlling morphology and final phase composition. PMID- 17737668 TI - Does ammonia hydrogen bond? AB - Spectroscopic characterizations of the stereochemistry of complexes of ammonia (NH(3)) have strongly confirmed some long-held ideas about the weak interactions of NH(3) while casting doubt on others. As expected, NH(3) is observed to be a nearly universal proton acceptor, accepting hydrogen bonds from even some of the weakest proton donors. Surprisingly, no evidence has been found to support the view that NH(3) acts as a proton donor through hydrogen bonding. A critical evaluation of the work that has been done to gather such evidence, as well as of earlier work involving condensed-phase observations, suggests that NH(3) might well be best described as a powerful hydrogen-bond acceptor with little propensity to donate hydrogen bonds. PMID- 17737669 TI - Direct observation of dissociated dislocations in garnet. AB - Dislocation core structures in garnet [grossularite (Ca(2.9)Fe(II)(0.1))(Al(1.9)Fe(III)(0.1)Si(3.0)O(12)] have been examined with near atomic resolution transmission electron microscopy. Dissociated dislocations have been observed as parallel a/4<111> partial dislocations that are separated by stacking faults. The partial dislocations have narrow cores ( approximately 3 burgers vectors), and the stacking fault zone between the narrow partial dislocations is apparently a low-energy configuration that results from the occupancy of previously unfilled dodecahedral and tetrahedral sites. Previous studies of garnet dislocations suggested that dissociation involves departures from garnet stoichiometry (that is, trace amounts of impurities), but evidence of detectable amounts of impurities has not been found even in the highest resolution images. These results have implications for mantle mineral rheology and transformations as well as for ceramics of material science interest. PMID- 17737670 TI - Horizontal plate motion: a key allocyclic factor in the evolution of the great barrier reef. AB - The Great Barrier Reef complex of northeastern Australia thins dramatically and becomes younger from north to south. These variations are a consequence of the Cenozoic northward movement of the Indian-Australian plate. The temperate climatic conditions that applied off northeast Australia during the early Tertiary were progressively replaced by tropical conditions. The present-day south-to-north facies distribution along the eastern Australian continental margin mimics the Cenozoic vertical facies sequence through the northern part of the Great Barrier Reef region. PMID- 17737671 TI - Quantitative three-dimensional optical tomographic imaging of supersonic flows. AB - Three-dimensional imaging of the density of nitrogen in a supersonic expansion from a nozzle by means of beam-deflection optical tomography is described. With a very simple apparatus, images could be obtained with high absolute accuracy, high spatial resolution, and wide dynamic range. PMID- 17737672 TI - Was venus wet? Deuterium reconsidered. AB - The ratio of deuterium to hydrogen on Venus has been accepted as proof of a wetter, more Earth-like past on that planet. However, the present-day water abundance and the nonthermal hydrogen escape flux on Venus imply that hydrogen is in a steady state and that a hydrogen source, most likely cometary infall, is present. An alternative interpretation of the D/H ratio is offered, in which the measured value is consistent with a steady-state evolution over the age of the solar system. No past water excess is required to explain the isotopic data. PMID- 17737673 TI - Stimulation of heterotrophic microplankton production by resuspended marine sediments. AB - Resuspended material experimentally derived from natural marine sediments and added to dark microcosms containing natural seawater stimulated the suspended microheterotrophs (bacteria and protozoa) to attain 2.6 times the biovolume of controls after 32 hours. Free bacteria benefited most from the stimulus, both numerically and volumetrically. Attached suspended bacteria also increased in number during the first 64 hours of the experiment; particles remaining in suspension became more densely packed with bacteria. This increased microbial production may be an important source of high-quality biomass for consumers in the nearshore zone, depending on the frequency, duration, and intensity of resuspension events in a given region. PMID- 17737674 TI - Response: the cerebellum and memory storage. PMID- 17737675 TI - Response: color vision and the retinex theory. PMID- 17737676 TI - Family affairs: domestic tyranny. PMID- 17737677 TI - A brief arousal: beyond the laboratory. PMID- 17737678 TI - Rapid radio emissions: superluminal radio sources. PMID- 17737679 TI - Behavioral evolution: evolutionary genetics of invertebrate behavior. PMID- 17737681 TI - Products & materials. PMID- 17737680 TI - Retinal function: the retina. PMID- 17737682 TI - Is There a Scientific Method? PMID- 17737683 TI - Undergraduate Origins of American Scientists. AB - An analysis of the college attendance or college choice for four high-aptitude, high-school senior samples suggests that the differential institutional productivity of scientists and scholars is a function of the differential college attendance, paternal vocational motivations, and their implied correlates among high-aptitude students. This formulation appears to be more probable for males than for females. The institutional productivity hypothesis proposed in previous studies is not supported by the present evidence (14). PMID- 17737685 TI - News of Science. PMID- 17737684 TI - Comparison of Closely Related Faunas. PMID- 17737686 TI - Detection of Rare-Earth Ions as Oxalates and Cupferrates. PMID- 17737687 TI - Meetings and Societies. PMID- 17737688 TI - Russian Scientific Information. PMID- 17737689 TI - Russian Scientific Information. PMID- 17737690 TI - EQUIPMENT NEWS. PMID- 17737691 TI - Transabdominal Amniocentesis. PMID- 17737692 TI - Transabdominal Amniocentesis. PMID- 17737694 TI - "Extation". PMID- 17737693 TI - Breeder reactor policy. PMID- 17737695 TI - Marihuana effects. PMID- 17737696 TI - Energy from biomass. PMID- 17737697 TI - The chemical composition of the sun. PMID- 17737698 TI - An experiment in earthquake control at rangely, colorado. AB - An experiment in an oil field at Rangely, Colorado, has demonstrated the feasibility of earthquake control. Variations in seismicity were produced by controlled variations in the fluid pressure in a seismically active zone. Precise earthquake locations revealed that the earthquakes clustered about a fault trending through a zone of high pore pressure produced by secondary recovery operations. Laboratory measurements of the frictional properties of the reservoir rocks and an in situ stress measurement made near the earthquake zone were used to predict the fluid pressure required to trigger earthquakes on preexisting fractures. Fluid pressure was controlled by alternately injecting and recovering water from wells that penetrated the seismic zone. Fluid pressure was monitored in observation wells, and a computer model of the reservoir was used to infer the fluid pressure distributions in the vicinity of the injection wells. The results of this experiment confirm the predicted effect of fluid pressure on earthquake activity and indicate that earthquakes can be controlled wherever we can control the fluid pressure in a fault zone. PMID- 17737700 TI - Blind medical student: overcoming preconceptions. PMID- 17737699 TI - Restored pictures of ganymede, moon of jupiter. AB - Restored pictures of Ganymede have been produced that have some identifiably reliable features and some identifiable artifacts. The latter arise from artifacts in parts of the red image data. Among the presumably reliable features are some mare-like objects (perhaps with some internal structure), and a few rather large, bright rings. Whether the latter are ice, or arise from near specular reflection from smooth surface features, is left for future investigation. One of the restoring methods used, maximum entropy, has been shown to be applicable to moderately extended images. In view of its short time requirements (30 seconds per picture), the method should be applicable to moderately larger images, for example with twice the given number of data points. PMID- 17737701 TI - Judging a handicapped applicant. PMID- 17737703 TI - NSF: Science Education Is Still in the Spotlight. PMID- 17737702 TI - Scientists and bureaucrats: a clash of cultures on FDA advisory panel. PMID- 17737704 TI - NSF Authorization Over One Hurdle. PMID- 17737705 TI - Nuclear Foes Fault Scientific American's Editorial Judgment in Publishing a Recent Article by Nobel Laureate Hans Bethe. PMID- 17737706 TI - Fourier transform: the revolution comes to infrared. PMID- 17737707 TI - Research news. AB - The Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy is the largest meeting devoted to chemical instrumentation in the United States, and probably the largest in the world. From 1 to 5 March, more than 7500 scientists gathered at the Cleveland Convention Center to listen to some 497 papers and to visit the booths of 324 instrument manufacturers and distributors. Another 3000 visited only the instrument exhibition. Because so many manufacturers exhibit their established instruments and introduce new ones at the Pittsburgh Conference (which is so named because it is sponsored by the Society for Analytical Chemists of Pittsburgh and the Spectroscopy Society of Pittsburgh even though it has been held in Cleveland for the past 9 years), it is an ideal place to examine trends in instrumentation and, thereby, current trends in chemistry. Many of those trends are discussed in the following stories. Other trends include the growing number of women participants. As recently as 5 years ago, there was only one woman among the manufacturer's representatives at the meeting. No figures are available this year, but women probably accounted for at least 5 percent of the sales force. Also the number of professional women visiting the exhibition was much greater than ever before. Another important trend was the enthusiasm of the visitors to the exhibition. Many of them seemed to have money in their pockets and to be ready to spend it, an indication that the instrument business-and, therefore, the physical sciences-will enjoy a year of healthy growth. PMID- 17737708 TI - The intelligent instrument: coming, but not yet here. PMID- 17737709 TI - Fluorescence spectroscopy: finally of interest. PMID- 17737710 TI - Surface analysis: multiple techniques for monolayers. PMID- 17737712 TI - Rain forest primates. PMID- 17737711 TI - Pittsburgh highlights. PMID- 17737713 TI - Interpreting burial customs. PMID- 17737714 TI - Macromolecules. PMID- 17737715 TI - Surfaces of solids. PMID- 17737716 TI - Vapor pressure of water at its triple point: highly accurate value. AB - The vapor pressure of water at its triple point was measured with greatly increased accuracy. The triple point was realized with newly designed equipment that enhanced the stability of the pressure and permitted any air released from solution to be removed by pumping. A diaphragm pressure transducer separated the water vapor from the helium used to transmit the pressure to the manometer. The pressure was measured with the National Bureau of Standards precision mercury manometer. The vapor pressure at the triple point was found to be 611.657 pascals with random uncertainties at the 99 percent confidence level of +/- 0.010 pascal. The systematic errors are estimated to be relatively insignificant. PMID- 17737717 TI - Stratospheric aluminum oxide. AB - Balloons and U-2 aircraft were used to collect micrometer-sized strato-spheric aerosols. It was discovered that for the past 6 years at least, aluminum oxide spheres have been the major stratospheric particulate in the size range 3 to 8 micrometers. The most probable source of the spheres is the exhaust from solid fuel rockets. PMID- 17737718 TI - Laboratory plate tectonics: a new experiment. AB - A "continent" made of a layer of hexagonally packed black polyethylene spheres floating in clear silicon oil breaks into subcontinents when illuminated by an ordinary incandescent light bulb. This experiment may be a useful model of plate tectonics driven by horizontal temperature gradients. Measurements of the spreading rate are made to establish the feasibility of this model. PMID- 17737719 TI - PRODUCTS and MATERIALS. PMID- 17737720 TI - Solar models. PMID- 17737721 TI - PCB's in Bald Eagle Eggs. PMID- 17737723 TI - IS MUTATION A FACTOR IN THE EVOLUTION OF THE HIGHER VERTEBRATES? PMID- 17737722 TI - Solar models. PMID- 17737724 TI - SECTION F-ZOOLOGY. PMID- 17737726 TI - THE YELLOW-FEVER MOSQUITO. PMID- 17737725 TI - A NEW WORLD FOR THE BLIND. PMID- 17737727 TI - COLOR-ASSOCIATIONS WITH NUMERALS, ETC. (FOURTH NOTE.) 1882-1906. PMID- 17737728 TI - THE PRIMEVAL ATMOSPHERE. PMID- 17737729 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17737731 TI - A COLORADO SCHOOL OF FORESTRY. PMID- 17737730 TI - THE GEOLOGICAL SURVEY OF ILLINOIS. PMID- 17737732 TI - THE MEMORIAL OF MAJOR WALTER REED, U. S. A. PMID- 17737733 TI - Sakharov appeal. PMID- 17737734 TI - Animals and research. PMID- 17737735 TI - Animals and research. PMID- 17737736 TI - International science. PMID- 17737737 TI - Probing Titan's Surface. PMID- 17737738 TI - Mutual deterrence or nuclear suicide. PMID- 17737739 TI - Chromospheres, transition regions, and coronas. AB - The increase in temperature outward from the surface of a stellar photosphere can be understood by looking at the local energy balance. The relatively high-density stellar photosphere is cooled effectively by radiative energy loss penetrating the optically thin corona. For the low-density chromosphere and corona, if the energy input cannot be balanced by radiative energy losses, the temperature will rise steeply, possibly up to 1 million degrees or more. Coronal heating and emission appear to be strongly influenced by magnetic fields, leading to large differences in x-ray emission for otherwise similar stars. Comparatively small variations are seen in the overall chromospheric emission of stars. Chromospheres are probably mainly heated by shock-wave energy dissipation, modified by magnetic fields. PMID- 17737740 TI - The continuing u.s. Helium saga. AB - Helium, resident in relatively high concentrations in certain natural gas fields in the United States, can be lost to the atmosphere when the natural gas is burned as fuel. In 1960, Congress amended the Helium Act of 1925 to provide for stripping natural gas of its helium, for purchase of the separated helium by the government, and for its long-term storage. In 1971, after about 28 billion cubic feet had been stored, the purchase program was terminated by the government, an action that unleashed several lawsuits and not a little acrimony. After more than a decade of controversy, much of the litigation has been concluded, much of the helium that could have been saved has been wasted to the atmosphere, and the gas fields supplying the helium are almost depleted. A new rich source of helium has been discovered in southwestern Wyoming that could ensure adequate supplies for many decades if an appropriate new federal policy on helium is developed and implemented. PMID- 17737741 TI - The Selling of the Space Station: All the Washington heavyweights voted "Nay" on the space station, but Reagan voted "Aye"; the "ayes" had it. PMID- 17737742 TI - A Comeback for Soviet Studies: After a 15-year decline, scholarship on the U.S.S.R. and East Europe is being bolstered by new programs and money. PMID- 17737743 TI - NSF Plans Help with Big Computer Problems: New program intended to give university researchers better access to supercomputers that are now out of reach. PMID- 17737744 TI - Is shortage of engineers a matter of definition? PMID- 17737745 TI - Unusual partners launch a biotechnology venture. PMID- 17737746 TI - San Diego Picks the Stars over Sodium. PMID- 17737747 TI - NIDA Sees Bias in Scientists' Drug Meeting. PMID- 17737748 TI - Contraband cells. PMID- 17737749 TI - Artificial Intelligence (I): Into the World: Al has become a hot property in financial circles; but do the promises have anything to do with reality? PMID- 17737750 TI - Fluvial processes: rivers. PMID- 17737751 TI - A mathematician: alan turing. PMID- 17737753 TI - Molecular biology of cancer: genes and proteins in oncogenesis. PMID- 17737752 TI - Sexual selection in insects: the evolution of insect mating systems. PMID- 17737754 TI - Some other books of interest: higher mathematics from an elementary point of view. PMID- 17737755 TI - Some other books of interest: vulture biology and management. PMID- 17737756 TI - Some Other Books of Interest: Darwin's Finches. PMID- 17737757 TI - Time-Resolved X-ray Absorption Spectroscopy of Carbon Monoxide-Myoglobin Recombination After Laser Photolysis. AB - Results are presented for the first time-resolved x-ray absorption measurements with a time resolution of 300 microseconds on a dynamically evolving chemical system. By synchronizing a neodymium: yttrium-aluminum-garnet pulsed laser with the bursts of x-rays emitted from the Cornell High Energy Synchrotron Source, it was possible to monitor at room temperature the recombination of carbon monoxide with myoglobin after laser photolysis. Changes in the pre-edge structure and in the position of the iron edge of this protein were detected as a function of time. PMID- 17737758 TI - Lead retention in zircons. PMID- 17737760 TI - COMMENT AND CRITICISM. PMID- 17737759 TI - Lead retention in zircons. PMID- 17737761 TI - THE PRESIDENT AND PROFESSOR AGASSIZ. PMID- 17737762 TI - BULGARIA AND BULGARIANS. PMID- 17737764 TI - AN HONOR TO AMERICAN OPTICIANS. PMID- 17737763 TI - WEST AFRICAN ISLANDS. PMID- 17737766 TI - EDWARDS'S BUTTERFLIES OF NORTH AMERICA. PMID- 17737765 TI - THE LATEST SLIDES IN THE WHITE MOUNTAINS. PMID- 17737768 TI - ASTRONOMICAL NOTES. PMID- 17737767 TI - LIPPS'S PSYCHOLOGICAL STUDIES. PMID- 17737769 TI - GEOGRAPHICAL NOTES. PMID- 17737770 TI - WASHINGTON LETTER. PMID- 17737771 TI - Woodhead and Hare's 'Pathological mycology.'. PMID- 17737772 TI - The color of the sky. PMID- 17737773 TI - Research at NIH: The Wooldridge Report. PMID- 17737774 TI - Letters to the Editor. PMID- 17737775 TI - Letters to the Editor. PMID- 17737776 TI - Old Ties with the Smithsonian. PMID- 17737777 TI - Full-Time Researchers in Universities. PMID- 17737778 TI - Reprints of Reprint Requests Requested. PMID- 17737779 TI - Why Bibliography? PMID- 17737780 TI - The Research and Development Pork Barrel. PMID- 17737781 TI - Lasers. PMID- 17737782 TI - Early Man in East Africa. PMID- 17737783 TI - Some Current Problems of Government Science Policy. PMID- 17737784 TI - Defector's Odyssey: Personal Look at Soviet-Bloc Science Provided by High-Ranking German Physicist. PMID- 17737785 TI - Congress: Subcommittee Surveys Effects of Federally Supported Research on Higher Education. PMID- 17737786 TI - Infrared Spectra as a Means of Determining Botanical Sources of Amber. AB - Comparison of infrared spectra of amber no older than Oligo-Miocene with present day resins provides convincing evidence as to source, especially with corroboration from paleobotanical remains and knowledge of living resin producers. Spectroscopy is also useful in establishing that amber in widely separated areas in the Cretaceous and Eocene is from the same botanical source, although it may not be possible to relate these older resins to those from present-day plant populations. PMID- 17737787 TI - Uranium-Series Ages of Pacific Atoll Coral. AB - The thorium-230: uranium-234 method of dating corals and oolites has been evaluated in detail for reliability, and various criteria have been established. Reliable ages for extensive coral formations of about 6000 and 120,000 years were obtained. A hiatus in the development of coral between 6000 and 120,000 years ago on the Pactfic atoll of Eniwetok implies that conditions did not permit coral growth during this period. The record prior to 120,000 years ago is not clear, probably because of a lack of unaltered samples. PMID- 17737788 TI - Uranium-Series Dating of Corals and Oolites from Bahaman and Florida Key Limestones. AB - Samples of fossil coral and oolite from marine formations of the Bahamas and the Florida Keys have been analyzed for their concentrations of uranium and thorium isotopes. Ages calculated from the ratio Th(230): U(234) clearly indicate periods of marine limestone formation at about 85,000, 130,000, and 190,000 years ago, implying that the surface of the ocean was then close to its present level. PMID- 17737789 TI - Tritium and Phosphorus-32 in High-Resolution Autoradiography. AB - The sensitivity of monolayers of Ilford L-4 nuclear emulsion to beta(-)-particles is approximately 0.20 grain per particle emitted for H(3), and 0.025 grain per particle for p(32). The sensitivity for thick layers is 1.3 grains per tritium beta(-)-particle emitted within the emulsion. In electron microscopic autoradiographs the maximum resolution is approximately 0.1 micron for H(3) and 0.3 micron for p(32). PMID- 17737790 TI - Reduction of Trimethylene Dipyridyl with Illuminated Chloroplasts. AB - Chloroplasts photochemically reduce 1,1'-trimethylene-2,2'-dipyridylium dibromide and concurrently form adenosine triphosphate. Reduced trimethylene dipyridyl in darkness will reduce spinach ferredoxin, Clostridium pasteurianum ferredoxin, nicotinamide-adenine dinucleotide phosphate, and other viologen-type dyes. PMID- 17737791 TI - Psychrometric Measurement of Leaf Water Potential: Lack of Error Attributable to Leaf Permeability. AB - A report that low permeability could cause gross errors in psychrometric determinations of water potential in leaves has not been confirmed. No measurable error from this source could be detected for either of two types of thermocouple psychrometer tested on four species, each at four levels of water potential. No source of error other than tissue respiration could be demonstrated. PMID- 17737792 TI - Active Uptake of Sodium by Softshell Turtles (Trionyx spinifer). AB - Aquatic softshell turtles (Trionyx spinifer spinifer) show a net active uptake of sodium from solutions of this cation as dilute as S micromoles per liter. This probably occurs in the pharynx, a site of aquatic respiration. Inhibition of active sodium transport by low temperatures causes an extreme lowering of the sodium concentration in the plasma. Other fresh-water turtles may utilize this mechanism of ionic regulation. The ultrastructure of the pharyngeal villi is similar to that of frog skin and toad bladder. PMID- 17737793 TI - Nature of the Excitatory Sarcoplasmic Reticular Junction. AB - The appositional regions between the surface membrane and sarcoplasmic reticulum in insects, decapod crustaceans, and barnacles are largely diadic and show a four layered structure which is roughly circular in surface view. Each consists of the 56-angstrom double-membrane of the in-termediary (here called excitatory) element, and the 75-A double-membrane of the cisternal element of the reticulum, separated by a space of about 100 A. A sheet of electron-dense material is found between the two elements, giving the superficial appearance of an additional membrane. The orbits of thin filaments around the thick filaments adjacent to both excitatory and reticular elements are incomplete on the contact side. Regularly spaced bridges connect the thick filaments with both the excitatory elements and cisternal elements and hold the diads in place during stretch and contraction. PMID- 17737794 TI - Mutation of the Blue-Green Alga, Anacystis nidulans. AB - Cells of Anacystis nidulans in the logarithmic phase of growth were briefly treated with the mutagen, N-methyl-N'-nitro-N-nitrosoguanidine, and plated under conditions suitable for single-cell growth. Selection of aberrant colonies and examination of the cultural characteristics of these clones suggest that mutants of at least several types are easily derivable in Anacystis. PMID- 17737795 TI - Lipase: Localization in Adipose Tissue. AB - Certain problems usually associated with the histochemistry of lipases are obviated by a technique that utilizes the endogenous blood chylomicrons and the cellular stores of triglyceride as substrates for the histochemical demonstration of lipolytic enzyme activity in situ. In spreads of mesenteric adipose tissue, the technique makes it possible to distinguish between lipoprotein lipase activity at sites in the capillaries and lipolysis occurring in the adipocytes. The selective anatomic lolization of the lipase reaction correlated with the functional state of the tissue, and the absence of reaction product in control mesenteries from starved mice or in heat-inactivated controls, support the validity of this histochemical reaction. PMID- 17737796 TI - Activity in Mammalian Peripheral Nerves during Supercooling. AB - Excised peripheral nerves from several species of mammals from interior Alaska continue to operate when supercooled to temperatures as low as -6 degrees C. In some nerves, spontaneous freezing begins before activity ceases. If the nerves are not allowved to remain in a partially or completely frozen state for a prolonged period they will regain their activity when rewarmed. PMID- 17737797 TI - Ultrastructure of Vegetative and Reproductive Apices of Chenopodium album. AB - The apical meristem of the vegetative shoot of Chenopodium album (lamb's quarters) exhibits alterations in cytoplasmic structure as early as 3 hours after the plant has been subjected to one photoinductive cycle which promotes flowering. The endo-plasmic reticulum shows an altered distribution and there is evidence of an increase in acid phosphatase production. Dictyosomes increase in number per cell by the end of the second inductive cycle. PMID- 17737798 TI - Ribosomes from Escherichia coli: Lack of Specificity for Viral RNA. AB - The class of ribosomes from Escherichia coli that associate with plant virus RNA in vitro can be separated from the bulk of ribosomes by gradient centrifugation. The relative activity for subsequent incorporation of amino acid into polypeptides directed by the viral RNA in comparison to that directed by polyuridylic acid is the same for that class as for the bulk of ribosomes. PMID- 17737799 TI - Alcohol Dehydrogenase in Drosophila melanogaster: Isozymes and Genetic Variants. AB - Alcohol dehydrogenase, in Drosophila melanogaster homozygous for the alleles Adh(F) or Adh(S), is found in three electrophoretically different forms. Adh' differs from Adh(5) in that isozymes with faster electrophoretic mobilities are present. In Adh(F)/Adh(S) heterozygotes, hybrid isozymes as well as the parental isozymes are present, indicating that the dehydrogenase may exist as a dimer of two polypeptide subunits. The gene, Adh, is located on the second chromosome, with a map position of 50.1 and a cytological position between 34E3 and 35D1. PMID- 17737800 TI - Nonspecific Binding of Complement by Digestion Fragments from Antiviral Gamma Globulin. AB - The nonspecificity of rabbit gamma-globulin (antibody) to western equine encephalitis virus and the non-specificity of normal rabbit gamma-globulin in complement-fixation tests with anti-gens prepared from chick-embryo cells infected with this virus and normal chick-embryo cells resided primarily in Porter's fragment III. Addition of complement to fragment III from the anti-body globulin, followed by inactivation of the added complement, abolished the complement-fixing ability of fragment III with both specific and nonspecific antigens. Similar treatment of the undigested antibody abolished its complement fixing ability with nonspecific antigen only. PMID- 17737801 TI - Respiratory Water Exchange in Two Species of Porpoise. AB - Measurements of the respiratory water exchanges of Tursiops truncatus and Lagenorhynchus obli-quidens indicate that these species lose, respectively, only 30 and 77 percent as much water through evaporation as would terrestrial mammals of the same body weight. Control of temperature and pressure within the respiratory system and a lower ventilation rate account for this relatively small loss of water. PMID- 17737802 TI - Stimulus Variables Determining Space Perception in Infants. AB - It was shown previously that infants who have neither reached nor crawled discriminate changes in spatial position on the basis of cues other than the projective size of objects displaced in space. It is now shown that binocular vision is not necessary for discrimination and that pictorial cues are not sufficient for discrimination. Parallax variables provide the information used by such infants for the discrimination of size and distance. PMID- 17737803 TI - Cerebral Temperature Changes Accompanying Sexual Activity in the Male Rat. AB - Cerebral temperature was continuously recorded in male rats during sexual activity. The temperature showed a persistent increase in the presence of females and a relatively brief, rapid increase during sexual intromission. Cerebral temperature may be usable as a sensitive measure of immediate and persisting motivational effects of transitory and longterm conditions of stimulation. PMID- 17737805 TI - Colston Symposium: Marine Geology and Geophysics. PMID- 17737804 TI - Hypothalamic Motivational Processes as Reflected by their Hippocampal Electrical Correlates. AB - Electrical stimulation of the same hypothalamnic point with current of mild or strong intensity produces opposite behavioral effects; moreover, interruption of either kind of stimulation invariably results in the appearance of powerful antagonistic aftereffects. There is a strict correlation between approach behavior and hippocampal theta rhythm on the one hand and withdrawal behavior and desynchronization on the other. The importance of the antagonistic aftereffects in the organization of conditional processes and in the interpretation of the "drive reduction" hypothesis is emphasized. PMID- 17737806 TI - Forthcoming Events. PMID- 17737807 TI - UNIVERSITY REGISTRATION STATISTICS. PMID- 17737808 TI - SUMMARY OF THE FIFTH ANNUAL REPORT OF THE CARNEGIE FOUNDATION. PMID- 17737809 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17737810 TI - THE PUBLIC HEALTH SERVICE. PMID- 17737811 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17737812 TI - THE AIR WE BREATHE IN BUILDINGS. PMID- 17737813 TI - "MUTATIONS" OF WAAGEN AND "MUTATIONS" OF DE VRIES OR "RECTIGRADATIONS" OF OSBORN. PMID- 17737814 TI - THE FIFTH ANNUAL REPORT OF THE PRESIDENT OF THE CARNEGIE FOUNDATION. PMID- 17737815 TI - SCIENTIFIC JOURNALS AND ARTICLES. PMID- 17737816 TI - THE TYPE OF COLUMBINA SPIX. PMID- 17737817 TI - ANOTHER SEX-LIMITED CHARACTER IN FOWLS. PMID- 17737819 TI - THE CHICAGO ACADEMY OF SCIENCES. PMID- 17737818 TI - THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE THE FORTY-THIRD GENERAL MEETING OF THE AMERICAN CHEMICAL SOCIETY AND SECTION C. PMID- 17737820 TI - Social Responsibility of Science. PMID- 17737821 TI - Social Aspects of Science: Preliminary Report of AAAS Interim Committee. PMID- 17737822 TI - Humble Oil Company Radiocarbon Dates I. PMID- 17737823 TI - News of Science. PMID- 17737824 TI - Are There Any "Acellular Animals"? PMID- 17737826 TI - Meetings and Societies. PMID- 17737825 TI - Exchange of Sodium Ion in Ulva lactuca. PMID- 17737827 TI - EQUIPMENT NEWS. PMID- 17737828 TI - Letters to the Editor. PMID- 17737829 TI - Political Principles and NIH. PMID- 17737830 TI - Programmed Instruction. PMID- 17737831 TI - Force-Free Body: A Thought Experiment. PMID- 17737833 TI - Letters to the Editor. PMID- 17737832 TI - Emotional Perils of Mathematics. PMID- 17737834 TI - Numerical Analysis: Pure or Applied Mathematics? PMID- 17737835 TI - International Technical Assistance. PMID- 17737837 TI - Chemical Communication in the Social Insects. PMID- 17737836 TI - Meteorites and Craters Campo del Cielo, Argentina. PMID- 17737838 TI - The Financial Status of National Merit Finalists. PMID- 17737839 TI - Defense: McNamara's Comptroller, Charles J. Hitch, Leaves after Four Pioneering Years at DOD. PMID- 17737840 TI - Aerospace: Congressional Study of AF Contractor Raises Questions About Proper Role of Nonprofits. PMID- 17737841 TI - Technologically, the Atlantic Community Exists. PMID- 17737842 TI - Radioactivity of the Columbia River Effluent. AB - Chromium-51 and zinc-65 were detected as far as 115 and 15 kilometers, respectively, from the mouth of the Columbia River; zinc-65 also was found at a few isolated stations. Zirconium-95 and niobium-95 from atmospheric fallout occurred in the river effluent but they were most abundant in surface waters further ofJshore. Distribution of the radionuclides is controlled largely by surface currents and by upwelling of sea water near the coast. PMID- 17737843 TI - Liquid Waves by Computer. AB - A numerical, fluid-dynamics technique for high-speed computers is described and illustrated. It applies to the solution of problems dealing with incompressible viscous fluids and involving nonsteady motions in several dimensions in space. The ability to handle free-surface boundary conditions allows waves to be studied through all phases of breaking and splashing, as well as a number of related phenomena. PMID- 17737844 TI - Color Adaptation of Edge-Detectors in the Human Visual System. AB - An aftereffect of color which depends on the orientation of lines in the test field may be obtained by presenting a horizontal grating of one color alternately with a vertical grating of a different color. Like the aftereffect of adaptation to chromatic fringes produced by prismatic spectacles, this aftereffect is visible in monochromatic light and fails to show inter-ocular transfer. It is suggested that both effects are to be understood in terms of color adaptation of orientation-specific edge-detectors. PMID- 17737846 TI - Forthcoming Events. PMID- 17737845 TI - Nonequilibrium Thermodynamics, Variational Techniques, and Stability. PMID- 17737847 TI - SCIENCE NEWS. PMID- 17737848 TI - THE SPECIES COMPLEX IN BIOLOGY AND EDUCATION. PMID- 17737849 TI - A SELF-LIMITING MECHANISM IN SYMPATHETIC HOMEOSTATIC ADJUSTMENT. PMID- 17737851 TI - "STARS" IN AMERICAN MEN OF SCIENCE. PMID- 17737850 TI - THE PACIFIC ENTOMOLOGICAL SURVEY. PMID- 17737852 TI - CHLORAZOL FAST PINK BKS. PMID- 17737853 TI - SOCIETIES AND MEETINGS. PMID- 17737854 TI - THE DENATURATION OF PROTEINS BY DETERGENTS AND BILE SALTS. PMID- 17737855 TI - RADIOACTIVE ION EXCHANGES IN LIVING PROTOPLASM. PMID- 17737856 TI - THE CONFIGURATION OF THE GLUTAMIC ACID OF ADENOCARCINOMA PROTEIN. PMID- 17737857 TI - POLIOMYELITIC VIRUS IN SEWAGE. PMID- 17737858 TI - DEMONSTRATION OF THE SHAPE OF CILIA IN NORMAL MOTION. PMID- 17737859 TI - A NEW MATERIAL FOR MOUNTING NERVE TISSUE SECTIONS IN PARAFFIN FOR SILVER STAINING OR RESTAINING. PMID- 17737860 TI - THE STATE UNIVERSITY AND RESEARCH. PMID- 17737861 TI - THE MOSELY EDUCATIONAL COMMISSION. PMID- 17737862 TI - THE FORMATION OF TOXIC PRODUCTS BY VEGETABLE ENZYMES. PMID- 17737863 TI - CONCERNING SPECTACLES. PMID- 17737864 TI - THE ASCENT OF WATER IN TREES. PMID- 17737865 TI - ASYMMETRON LUCAYANUM IN BERMUDA. PMID- 17737867 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17737866 TI - THE ENDOSPERM ENZYME OF PHCENIX DACTYLIFERA--PRELIMINARY REPORT. PMID- 17737868 TI - STOMACH STONES AND FOOD OF PLESIOSAURS. PMID- 17737870 TI - THE CULTIVATION OF COTTON IN THE WEST INDIES. PMID- 17737869 TI - THE ALPINE LABORATORY OF THE BOTANICAL SEMINAR OF THE UNIVERSITY OF NEBRASKA. PMID- 17737871 TI - DR. J. C. MCCONNELL. PMID- 17737873 TI - The Shortage of Scientific Personnel. PMID- 17737872 TI - Proposed National Science Foundation Act, 1947: S. 526. PMID- 17737874 TI - First Report of the U. S. Atomic Energy Commission. PMID- 17737875 TI - Chromatolytic Effect of Cerebrospinal Fluid Following Cerebral Concussion. PMID- 17737876 TI - Synthesis of Tyrosine Labeled With C14. PMID- 17737877 TI - Electrometric Studies in Women With Malignancy of Cervix Uteri. PMID- 17737878 TI - Stimulation of Oleoresin Flow in Pines by a Fungus. PMID- 17737879 TI - The Effect of Combining Sodium Benzoate With Oral Penicillins. PMID- 17737880 TI - Action of Thiamine Applied Directly to the Cerebral Cortex. PMID- 17737881 TI - Bacillary Dysentery and Chronic Ulcerative Colitis in World War II. PMID- 17737883 TI - The Maceration of Woody Tissue With Acetic Acid and Sodium Chlorite. PMID- 17737882 TI - A Tunnel Clamp-for Use in Controlling Infusion Rates. PMID- 17737884 TI - An Improved Alcohol Check for Rat Metabolism Apparatus. PMID- 17737885 TI - A Simplified Encephalophone. PMID- 17737887 TI - A good word for realities. PMID- 17737886 TI - This week in science. PMID- 17737888 TI - High-speed lightwave transmission in optical fibers. AB - There has been considerable progress in the telecommunications technology based on the transmission of lightwaves through optical fibers. Systems experiments in the 1.55-micrometer band have now demonstrated the capability of transmitting at rates as high as 2 gigabits per second over fiber lengths exceeding 100 kilometers, without the use of repeaters to boost the signal. Elements of this progress are advances in the fabrication of low-loss single-mode fibers, in the spectral control of semiconductor junction lasers assuring single-frequency operation, and in high-speed detectors and receivers. PMID- 17737889 TI - Hard Times in Magnetic Fusion: Two straight years of budget cuts are forcing a reexamination of the program's goals and timetable; major machines could be mothballed. PMID- 17737891 TI - Dispute over Soviet Testing Heats Up. PMID- 17737890 TI - New French law boosts industrial r&d. PMID- 17737892 TI - Hawaiian Rainforest Being Felled: Woodchipping operation decried by scientists as sorry model for bioenergy development. PMID- 17737893 TI - Stockman relents on landsat. PMID- 17737894 TI - Environmental leadership in state of flux. PMID- 17737895 TI - New york mayor honors scientists. PMID- 17737896 TI - Pentagon claims export controls save billions. PMID- 17737897 TI - Fractal Fingers in Viscous Fluids: Highly unstable viscous fingers break up into many-branched structures that are suggestive of fractal geometry. PMID- 17737898 TI - A unit for social analysis: households. PMID- 17737899 TI - An ancient lake: lake biwa. PMID- 17737900 TI - Marine ecology: marine ecological processes. PMID- 17737901 TI - Lichen biology: biology of lichenized fungi. PMID- 17737902 TI - A theory for el nino and the southern oscillation. AB - A coupled atmosphere-ocean model is presented for El Nino and the Southern Oscillation that reproduces its major features, including its recurrence at irregular intervals. The interannual El Nino-Southern Oscillation cycle is maintained by deterministic interactions in the tropical Pacific region. Ocean dynamics alter sea-surface temperature, changing the atmospheric heating; the resulting changes in surface wind alter the ocean dynamics. Annually varying mean conditions largely determine the spatial pattern and temporal evolution of El Nino events. PMID- 17737903 TI - The diversification of the leguminosae: first fossil evidence of the mimosoideae and papilionoideae. AB - The legumes are an important group of flowering plants with a poorly documented evolutionary history. New fossil evidence provides data on the timing of the origin of the two derived subfamilies of legumes (the Mimosoideae and Papilionoideae). These data strongly suggest the importance of bee pollinators during a major period of angiosperm diversification. PMID- 17737904 TI - Chronic herbivory: impacts on architecture and sex expression of pinyon pine. AB - Pinyon pine, Pinus edulis (Engelm.), in Northern Arizona is exposed to recurring high levels of herbivory by the moth Dioryctria albovitella (Hust.). During a 3 year period, infested trees experienced on average a 30 percent reduction in annual shoot production. This herbivory affects tree architecture, growth rate, reproductive output, and sexual expression. Less infested trees produce 47 percent more trunk wood, 43 percent more branch wood, and are monoecious. Architectural changes in infested trees can result infunctionally male plants due to a complete loss of normal female cone-bearing ability. When herbivores are experimentally removed, normal growth and reproduction patterns resume. These strong herbivore impacts should represent a potent selection pressure in the evolution of host traits. PMID- 17737905 TI - Late pleistocene faunal extinctions in southern patagonia. AB - Major environmental changes recorded in pollen records from various sites in southern Patagonia and Tierra del Fuego are also reflected in pollen and cuticle data from dung of the late Pleistocene groundsloth. The most prominent change was the large-scale reduction of steppe environment about 10,000 years ago, which coincides with the latest dates for extinctions of many large grazers such as the giant groundsloth. Stress on food resources for all the large grazers may well have hastened their extinction. Hunting pressure by paleoindians may have been the final blow. PMID- 17737906 TI - Male reproductive parasitism: a factor in the africanization of European honey bee populations. AB - Africanized drone honey bees (Apis mellifera) migrate into European honey-bee colonies in large numbers, but Africanized colonies only rarely host drones from other colonies. This migration leads to a strong mating advantage for Africanized bees since it both inhibits European drone production and enhances Africanized drone production. PMID- 17737908 TI - SCIENCE NEWS. PMID- 17737907 TI - THE BIOLOGICAL BASIS OF INDIVIDUALITY. PMID- 17737909 TI - RECOGNITION OF MINERALOGISTS. PMID- 17737911 TI - SCRIPTA MATHEMATICA. PMID- 17737910 TI - MORE BRAINS AND LESS MONEY. PMID- 17737912 TI - MICROPHOTOGRAPHS AND PHOTOMICROGRAPHS. PMID- 17737913 TI - THE OHIO ACADEMY OF SCIENCE. PMID- 17737914 TI - THE SIGNIFICANCE OF THE ADRENALS FOR ADAPTATION TO MINERAL METABOLISM. PMID- 17737915 TI - THE DISAPPEARANCE OF INJECTED EPINEPHRINE IN THE ANIMAL BODY. PMID- 17737916 TI - MENINGOCOCCUS INFECTION OF THE CHICK EMBRYO. PMID- 17737917 TI - ENVIRONMENTAL CONDITIONS INFLUENCING THE DEVELOPMENT OF TOMATO POCKETS OR PUFFS. PMID- 17737918 TI - Science and Security. PMID- 17737919 TI - Recent Discoveries in the Egyptian Faiyum and Sinai. PMID- 17737920 TI - Fred Conrad Koch 1876-1948. PMID- 17737921 TI - Symposium on Problems of the Ocean. PMID- 17737922 TI - An Experimental and Theoretical Approach to the Mechanism of Cocaine Action. PMID- 17737923 TI - Confirmatory Analysis of the "Lost" Italian Varnish. PMID- 17737924 TI - Loss of Radioactivity From Barium Carbonate Samples. PMID- 17737925 TI - A Piston Recorder for Small Volume Changes. PMID- 17737926 TI - Radiation From a Flask Containing Various Amounts of Radioactive Phosphorus. PMID- 17737927 TI - Cold, fresh water. PMID- 17737928 TI - The case for diversity. PMID- 17737929 TI - K-T boundary issues. PMID- 17737930 TI - K-T boundary issues. PMID- 17737931 TI - Corrections and clarifications. AB - The Random Sample item "The brain behind that happy face" (15 Oct., p. 336) refers to a paper by Paul Ekman and Richard Davidson. That paper appeared in the September 1993 issue of Psychological Science, a journal of the American Psychological Society. PMID- 17737932 TI - Response. PMID- 17737933 TI - NIH Confronts New Fraud Allegations. PMID- 17737934 TI - Fusion research at the crossroads. PMID- 17737935 TI - Europeans Launch Effort to Extend JET. PMID- 17737936 TI - Fire threatens galapagos tortoises. PMID- 17737938 TI - Video conferencing lets physicists go head to head. PMID- 17737937 TI - French scientists thwart plan for research reforms. PMID- 17737939 TI - Prehistoric bird kill. PMID- 17737940 TI - Eyeing European crops. PMID- 17737942 TI - Horn of plenty. PMID- 17737941 TI - Fired mobil scientist awarded $7 million. PMID- 17737943 TI - Bugs are sweet on crop waste. PMID- 17737944 TI - Money offered in spinal surgery trial. PMID- 17737945 TI - NSF Audit Wins Plaudits. PMID- 17737946 TI - Taking a gamble on the top quark. PMID- 17737947 TI - Volcanoes with bad hearts are tumbling down all over. PMID- 17737948 TI - Sea turtles master migration with magnetic memories. PMID- 17737949 TI - Throttling back the great lava floods? PMID- 17737950 TI - X-rays Make a Smooth Move. PMID- 17737951 TI - The entropic cost of bound water in crystals and biomolecules. PMID- 17737952 TI - A catastrophic death assemblage and paleoclimatic implications of pliocene seabirds of Florida. AB - A deposit of fossil seabirds from the late Pliocene of Florida includes more than 130 skeletons of an extinct cormorant that is related phylogenetically to Recent species currently restricted to the eastern north Pacific. Evidence suggests the birds died in a single catastrophic event, perhaps a red tide. The fossil cormorant, along with other extinct seabirds and marine mammals, supports molluscan evidence for cold-water upwelling along the Florida Gulf Coast during the Pliocene. A decline in species richness of marine vertebrates throughout the Pliocene of Florida coincides with cessation of upwelling after emergences of the Panamanian Land Bridge. PMID- 17737953 TI - A seismotectonic model for the 300-kilometer-long eastern tennessee seismic zone. AB - Ten years of monitoring microearthquakes with a regional seismic network has revealed the presence of a well-defined, linear zone of seismic activity in eastern Tennessee. This zone produced the second highest release of seismic strain energy in the United States east of the Rocky Mountains during the last decade, when normalized by crustal area. The data indicate that seismicity produced by regional, intraplate stresses is now concentrating near the boundary between relatively strong and weak basement crustal blocks. PMID- 17737954 TI - Detection of large prehistoric earthquakes in the pacific northwest by microfossil analysis. AB - Geologic and palynological evidence for rapid sea level change approximately 3400 and approximately 2000 carbon-14 years ago (3600 and 1900 calendar years ago) has been found at sites up to 110 kilometers apart in southwestern British Columbia. Submergence on southern Vancouver Island and slight emergence on the mainland during the older event are consistent with a great (magnitude M >/= 8) earthquake on the Cascadia subduction zone. The younger event is characterized by submergence throughout the region and may also record a plate-boundary earthquake or a very large crustal or intraplate earthquake. Microfossil analysis can detect small amounts of coseismic uplift and subsidence that leave little or no lithostratigraphic signature. PMID- 17737955 TI - The last deglaciation event in the eastern central arctic ocean. AB - Oxygen isotope records of cores from the central Arctic Ocean yield evidence for a major influx of meltwater at the beginning of the last deglaciation 15.7 thousand years ago (16,650 calendar years B.C.). The almost parallel trends of the isotope records from the Arctic Ocean, the Fram Strait, and the east Greenland continental margin suggest contemporaneous variations of the Eurasian Arctic and Greenland (Laurentide) ice sheets or increased export of low-saline waters from the Arctic within the East Greenland Current during the last deglaciation. On the basis of isotope and carbon data, the modern surface- and deep-water characteristics and seasonally open-ice conditions with increased surface-water productivity were established in the central Arctic at the end of Termination lb about 7.2 thousand years ago or 6,000 calendar years B.C.). PMID- 17737956 TI - Effects of manipulated diet on size and performance of brachyuran crab claws. AB - Crabs grown experimentally on fully shelled prey developed larger and stronger claws than those raised on nutritionally equivalent unshelled prey. When one claw was immobilized, claws also became asymmetrical. These use-induced changes differ from skeletal remodelling in vertebrates and many invertebrates because changes in the rigid exoskeleton can occur only after molting, and claw muscle mass must be reduced substantially before the molt. Such short-term adaptive responses to environmental stimuli, if heritable, could yield long-term evolutionary changes in claw size and, if combined with behavioral biases toward one side (handedness), could also promote the evolution of claw dimorphism. PMID- 17737958 TI - Vignettes: dire predictions. PMID- 17737957 TI - Ecological comprehensiveness. PMID- 17737960 TI - Diamond-making. PMID- 17737959 TI - Intergradations. PMID- 17737961 TI - Human rights and life sciences. PMID- 17737962 TI - Products & materials. PMID- 17737963 TI - Some Problems of Human Ecology in Polar Regions. PMID- 17737965 TI - COMMENTS by Readers. PMID- 17737964 TI - A System of Nomenclature for Isotopic Compounds. PMID- 17737966 TI - Chloromycetin, a New Antibiotic From a Soil Actinomycete. PMID- 17737967 TI - Chloromycetin, an Antibiotic With Chemotherapeutic Activity in Experimental Rickettsial and Viral Infections. PMID- 17737968 TI - Initiation of the Cone Gall of Witch Hazel. PMID- 17737969 TI - A Relationship Between Cystine and Pyridoxal or Pyridoxamine in the Nutrition of Certain Bacteria. PMID- 17737970 TI - Role of Inhibitors in Soybean. PMID- 17737971 TI - Protection of Synaptic Transmission Against Block by Nicotine. PMID- 17737972 TI - Effect of Benzene Hexachloride on the Flavor of Poultry Meat. PMID- 17737973 TI - In Vitro Resistance of the Genus Bacteroides to Streptomycin. PMID- 17737974 TI - A Contact Culture Method for Detecting Molds on Surfaces. PMID- 17737975 TI - A Method for Determining the Volume of Small Solid Objects. PMID- 17737976 TI - The Color Reactions of Sulfonamides With beta-Naphthoquinone-4-Sulfonate. PMID- 17737977 TI - Recording Uterine Contraction Patterns in Pregnant Women: Application of the Strain Gage in a Multichannel Tokodynamometer. PMID- 17737978 TI - Freezing Points of Cobalt and Nickel and a New Determination of Planck's Constant C2. PMID- 17737979 TI - Letters. PMID- 17737980 TI - Letters. PMID- 17737981 TI - Letters. PMID- 17737982 TI - Environment: "goods" and "bads". PMID- 17737983 TI - Walter reed papers. PMID- 17737984 TI - Science: endless horizons or golden age? PMID- 17737986 TI - Magnetic resonances and waves in simple metals. PMID- 17737985 TI - Dormancy of trees in winter. AB - Early dormancy involves a number of phenomena: cessation of active growth, formation of terminal buds, formation of abscission layers in leaves, development of cold resistance, development of winter rest (a chilling requirement), and leaf fall. The buds of some tree species (or some races of a species) have a true rest or winter chilling requirement; usually the roots do not; perhaps the cambium does not. There is a wide range of genetic variation within and between species in response to photoperiod, winter chilling, water nutrients, and other environmental factors which affect the dormancy condition of plants. During the period of winter rest there are many metabolic and developmental processes going on in the buds and twigs. These processes include respiration, photosynthesis, some cell division, enzyme synthesis, production of growth stimulators, and dissipation of growth inhibitors. Dormancy of trees can be divided arbitrarily into three phases: early rest, winter rest, and after-rest. Each of these phases is marked by a distinct set of physiological processes. The transition between the three phases is gradual. Some processes of after-rest can proceed even though the winter chilling requirement (winter rest) of a tree has not been completed fully. Evidence from grafting experiments and chemical treatments to break winter rest, and studies of genetic variability indicate that the processes and phenomena of dormancy are at least partially independent of each other. Different buds and branches and other parts of the same plant may initiate dormancy, break dormancy, and renew vegetative growth independently. Initiation and cessation of dormancy can be triggered by a number of environmental variables: photoperiod, temperature, nutrition, water, an array of chemicals, and shock treatments. Dormancy regulation must either involve a variety of receptors or involve receptors that are responsive to a variety of stimuli. Unless dormancy is defined in a highly restricted sense (that is, possession of chilling requirement), it is hard to conceive of a single receptor or regulator that controls all of the phenomena of dormancy. A large number of genes are definitely involved and hence a large number of enzymes. The kinds of enzymes, their numbers, and their concentrations can be regulated by manipulating the environment. PMID- 17737987 TI - State radiation law loses in court. PMID- 17737988 TI - AAAS Convention: Radicals Harass the Establishment. PMID- 17737990 TI - New journals received. PMID- 17737989 TI - ACE: Rating of Graduate Programs Shows Little Change in Status Quo. PMID- 17737991 TI - Paleotemperature Variations across the Plio-Pleistocene Boundary. AB - Strong variations in the O(18)/O(16) and C(13)/C(12) ratios occur through the type section for the Plio-Pleistocene boundary, but the boundary itself is not characterized by unusual isotopic gradients. PMID- 17737992 TI - Amorphous ice: density and reflectivity. AB - Amorphous ice prepared under a wide range of conditions has a density, determined from its buoyancy in liquid oxygen, of 0.94+/-0.02 gram per cubic centimeter, the same as that of ordinary hexagonal ice, with no indication of the glassy superdense ice (2.32 grams per cubic centimeter) reported recently. The diffuse reflectivity shows a small increase as the ice crystallizes at 153 degrees K. This increase is followed by a much larger increase (probably associated with crystal growth) as the sample warms, and the reflectivity reaches a maximum well below the melting temperature. Although the ice deposits appear translucent, the specular reflectivity is low, thus indicating a dull rather than a glassy surface. PMID- 17737994 TI - Amophous clay materials. PMID- 17737993 TI - Pinocytosis and membrane dilation in uranyl-treated plant roots. AB - Electron-dense crystals formed in plant roots exposed to uranyl acetate have been used to identify binding sites and to follow the pinocytotic uptake of uranyl in the oat rootcap. Before uranyl enters the protoplast, the plasmalemma is greatly dilated. After uranyl is sequestered in vacuoles, the tonoplast is similarly dilated. PMID- 17737995 TI - A transition for science. PMID- 17737996 TI - Molecular Genetics of the Bithorax Complex in Drosophila melanogaster. AB - The bithorax complex in Drosophila melanogaster is a cluster of homeotic genes that specify developmental pathways for many of the body segments of the fly. The DNA of the bithorax complex has been isolated, and a region of 195,000 base pairs that covers the left half of the complex is described here. The lesions associated with many of the bithorax complex mutants have been identified, and most are due to DNA rearrangements. Most of the spontaneous mutants have insertions of a particular mobile element named "gypsy." This element affects the functions of sequences removed from the site of insertion. Mutant lesions for a given phenotypic class are distributed over large DNA distances of up to 73,000 base pairs. PMID- 17737997 TI - The Search for a Nuclear Sanctuary (I): Millions of dollars are pouring into a series of programs that might one day recapture U.S. strategic superiority. PMID- 17737998 TI - How LOFT Stayed Afloat at DOE. PMID- 17737999 TI - Airplane Fire Safety Debate Rekindled: Critics charge the FAA is still dragging its feet in requiring stiffer standards. PMID- 17738001 TI - Merrell dow stops marketing bendectin. PMID- 17738000 TI - More tales from the academic pork barrel. PMID- 17738003 TI - How Did Vertebrates Take to the Air?: Aerodynamic analysis has produced novel support for the cursorial, as opposed to the arboreal, theory of the origin of birds. PMID- 17738002 TI - Survey Shows R & D Up Even if Sales Were Down. PMID- 17738004 TI - The Infrared Astronomy Satellite (II): IRAS is making the first all-sky survey in the infrared: the results, although slow in coming, should be dramatic. PMID- 17738006 TI - Opportunities in science searches for exemplary programs. PMID- 17738005 TI - Science 82 wins award for excellence. PMID- 17738007 TI - PIO Directory. PMID- 17738008 TI - Report documents changes in u.s. Professional work force. PMID- 17738009 TI - 1982 aaas summary financial statements. PMID- 17738012 TI - Linnaeus viewed from sweden: linnaeus. PMID- 17738010 TI - A nobel retrospective: science, technology and society in the time of alfred nobel. PMID- 17738011 TI - Southern mammals: Mammalian biology in South america. PMID- 17738013 TI - Is titan wet or dry? AB - Titan's dense and cold nitrogen atmosphere contains a small amount of methane under conditions at least approaching those at which one or both constituents would condense. The possibility of methane and nitrogen rain clouds and global methane oceans has been discussed widely. From specific features of radio occultation and other Voyager results, however, it is concluded that nitrogen does not condense on Titan and that Titan has neither global methane oceans nor a global cloud of liquid methane droplets. Certain results indirectly support the conjecture that methane does not condense at any location. However, other considerations favor a methane ice haze high in the troposphere, and liquid and solid methane might exist on the surface and as low clouds at polar latitudes. PMID- 17738014 TI - Oceans on titan? AB - If global oceans of methane exist on Titan, the atmosphere above them must be within 2 percent of saturation. The two Voyager radio occultation soundings, made at low latitudes, probably occurred over land, since they imply a relative humidity less, similar 70 percent near the surface. Oceans might exist at other low-latitude locations if the zonal wind velocities in the lowest 3 kilometers are X(3)Delta difference (~ 580 cm(-1)) in TiO measured by Phillips. Most of the transition-metal oxides have such low-lying levels, and they must be taken into consideration in any calculation of thermodynamic effects at high temperature. It appears that the study of emission spectra in the infrared at 4 degrees K may be one approach to this problem, and an attempt is now being made to confirm the TiO value in order to test the method. Perhaps the greatest advantage of matrix-isolation is the fact that it allows study of these molecules or of any molecules difficult to produce in a microwave cavity-by electron paramagnetic-resonance spectroscopy. Study of molecules by this means can provide information about ground state wave functions that is not obtainable by optical spectroscopy, as illustrated by the investigation of ScO, YO, and LaO. Also, it seems likely that the preferential orientation of molecules in matrices, which is probably achievable in most cases, will be a valuable asset in the study of the magnetic properties of molecules by electron-paramagneticresonance spectroscopy, regardless of whether the molecules are "hot" or "cold" (60). PMID- 17738211 TI - A Larger Scope for AEC Laboratories. PMID- 17738214 TI - Chemical and biological warfare (I): the research program. AB - Biological warfare is the intentional use of living organisms or their toxic products to cause death, disability, or damage in man, animals, or plants. The target is man, either by causing his sickness or death, or through limitation of his food supplies or other agricultural resources. Man must wage a continuous fight to maintain and defend himself, his animals, and his plants in competition with insects and microorganisms. The object of BW is to overcome these efforts by deliberately distributing large numbers of organisms of native or foreign origin, or their toxic products, taking full advantage of the ability to utilize more effective methods of dissemination and unusual portals of entry. BW has been aptly described as public health in reverse.-"Effects of Biological Warfare Agents," pamphlet published by Department of Health, Education, and Welfare, July 1959. PMID- 17738216 TI - Tax laws: conservationists must step gingerly on capitol hill. PMID- 17738215 TI - University of Pennsylvania: It's Hard To Kick The Habit. PMID- 17738217 TI - Representative fogarty dies at 53. PMID- 17738219 TI - Heart research program. PMID- 17738218 TI - H. G. Wells: he was a seer but a disappointed scientist. PMID- 17738221 TI - Marine dolomite of unusual isotopic composition. AB - A piston core taken off of the coast of Oregon in 358 meters of water contained an indurated calcareous layer composed partly of dolomite with a composition Ca(58.7)Mg(41.3). Dolomites of this chemical composition are typical of the supratidal environment. However, the dolomite has isotopic composition delta0(18) = 5.8 per mille, deltaC(13) = 35.1 per mille relative to the Chicago PDB-I standard. The unusual carbon isotope ratio is similar to that of calcites produced as a byproduct of bacterial breakdown of hydrocarbons. PMID- 17738220 TI - Tracks of cosmic rays in plastics. AB - Cosmic ray nuclei have been observed with the use of plastic trackdetecting solids in satellites and high-altitude balloon flights. Nuclear emulsions in the stacks of plastic sheets allowed the positive identification of cosmic raynuclei as light as nitrogen. The most striking new information was the failure to observe relativistic iron nuclei, a result which has led to an advance in the understanding of track registration criteria. PMID- 17738222 TI - Volcanic sunset-glow stratum: origin. AB - Reexamination of the phenomenon of volcanic-dust sunsets, as typified by the Krakatoa event, supports a theory that the scattering layer is produced by the interaction of ozone and sulfur dioxide in much the same manner as is the normal "Junge"aerosol layer at 20 kilometers. PMID- 17738223 TI - Superconductivity and the d-Shell. AB - The various isotope effects on the superconducting transition temperature of Mo(2)B and W(2)B have been measured. Together with resistivity data they indicate that the d-shell forms a highly stable electron configuration for molybdenum and tungsten. This leads to an understanding of high superconducting transition temperatures. PMID- 17738224 TI - Biotite flakes: alteration by chemical and biological treatment. AB - Biotite alteration under acid conditions proceeds differently from the generally accepted pathway of transformation to vermiculite in which hydrated cations cause interlayer expansion, resulting in a dark-colored peripheral band on mica particles. Acid solutions of synthetic or biologic origin remove octahedral ions, leaving a fragile matrix of amorphous material. PMID- 17738225 TI - Detergents in membrane filters. AB - Membrane filters from several manufacturers contain detergents. Cells cultured in media filtered through washed filters had higher plating efficiencies and a higher percentage of differentiation than cells cultured in media filtered through unwashed filters. PMID- 17738226 TI - Reversible Aggregation of alpha-Gliadin to Fibrils. AB - Acetic-acid (0.01 molar) extracts of wheat flour contain fibrils of alpha-gliadin which are about 80 angstroms thick and up to several thousand angstroms long. These fibrils dissociate to globular protein subunits at very low ionic strength and low pH. The fibrils can be reformed by increasing the pH to 5.1 and the ionic strength to about 0.005. PMID- 17738227 TI - Diphenamid metabolism in plants. AB - Diphenamid, a herbicide, is metabolized to N-methyl 2,2-diphenylacetamide and 2,2 diphenylacetamide by the common soil fungi Trichoderma viride and Aspergillus candidus within 48 hours. The two metabolites are more toxic than diphenamid to both tomato and barnyard-grass seedlings under sterile conditions. This finding indicates that the phytotoxic moiety is not diphenamid but one of its metabolites probably the N-methyl derivative. PMID- 17738228 TI - Cellular dynamics: hormones. PMID- 17738229 TI - "Wasted" water. PMID- 17738230 TI - Recombinant DNA molecules. PMID- 17738231 TI - Ely s. Parker. PMID- 17738232 TI - Mushroom poisoning. PMID- 17738234 TI - Two digit inflation. PMID- 17738233 TI - References and unreferences. PMID- 17738235 TI - Thermal structure of the lithosphere: a petrologic model. AB - A preliminary evaluation of the thermal history of the upper mantle as determined by petrologic techniques indicates a general correspondence with theoretically derived models. The petrologic data supply direct information which may be used as an independent calibration of calculated models, serve as a base for evaluating the assumptions of the theoretical approach, and allow more careful selection of the variables describing mantle thermal properties and processes. Like the theoretical counterpart, the petrological approach indicates that the lithosphere is dominated by two thermal regimes: first, there is a continental regime which cools at rates of the order of 10(9) years and represents the longterm cooling of the earth. Secondly, superimposed on the continental evolution is the thermal event associated with the formation of an oceanic basin, and which may be thought of as a 10(8) year convective perturbation on the continental cycle. Of special interest is petrologic evidence for a sudden steepening of the thermal gradients across the lithosphere-asthenosphere boundary not seen in the theoretical models. The unexpected change of slope points to the need for a critical reevaluation of the thermal processes and properties extant in the asthenosphere. The potential of the petrologic contribution has yet to be fully realized. For a start, this article points to an important body of independent evidence critical to our understanding of the earth's thermal history. PMID- 17738236 TI - Plutonium (I): questions of health in a new industry. PMID- 17738237 TI - On Inhaling Plutonium: One Man's Long Story. PMID- 17738238 TI - NSF Gets a Record $768 Million. PMID- 17738239 TI - A "giant step" in power pricing. PMID- 17738241 TI - Point of view. PMID- 17738240 TI - Jury selection: social scientists gamble in an already loaded game. PMID- 17738243 TI - Metrology: A More Accurate Value for Avogadro's Number. PMID- 17738242 TI - Complex environments: effects on brain development. PMID- 17738244 TI - Secular variations in the abundances of heavy nuclei in cosmic rays. AB - The ratios of fluxes of heavy cosmic-ray nuclei [(30 2] and for the 111.22-megahertz transition (F = 1 --> 1) in the galactic radio source W49, one of the brightest hydroxyl emission sources. No sulfur hydride emission lines with half-power widths of 130 hertz or greater were detected with the 1000-foot Arecibo antenna. The upper limits established with 100-hertz filters were 50 and 60 flux units (1 flux unit= 10(26) watt meter(-2) hertz(-1)), respectively, for the two lines. PMID- 17738364 TI - Nitrogen abundances in chondritic meteorites. AB - Carrier-gas fusion extractions of total nitrogen in 22 chondritic meteorites indicate a wide variation in total nitrogen contents, ranging from 660 parts per million for an enstatite chondrite to 18 parts per million for an ordinary chondrite. Total nitrogen and total carbon contents of individual chondrites do not show a positive correlation. PMID- 17738365 TI - Gravitational mechanism for sea-floor spreading. AB - The gravitational attraction of the continents produces a force field at the surface of the earth, similar in geometry to lithospheric displacements deduced from studies of earthquake focal mechanisms. PMID- 17738366 TI - Seismic Waves Reflected from Discontinuities within Earth's Upper Mantle. AB - Precursors to normtial seismic waves of the PKPPKP type in the distance range of 55 degrees to 75 degrees are ascribed to reflection of this phase from within the earth's upper mantle. The new observations confirm the existence of a sharply defined transition zone, probably worldwide in extent, at a depth of approximately 650 kilometers. These data are shown to be a useful tool for the study of upper mantle structure on a global basis. PMID- 17738367 TI - Potassium-sodium ratios in aqueous solutions and coexisting silicate melts. AB - Silicate melts were equilibrated with aqueous chloride solutions at temperatures between 770 degrees and 880 degrees C and a total pressure of 1.4 to 2.4 kilobars. The ratio of potassium to sodium in the aqueous phase was (0.74 +/- 0.06) times the corresponding ratio in the coexisting melt over the entire range of temperature and pressure for all chloride concentrations between 0.2 and 4.2 moles per kilogram. PMID- 17738368 TI - GEODETIC OPERATIONS IN THE UNITED STATES. PMID- 17738369 TI - THE AMERICAN MORPHOLOGICAL SOCIETY. PMID- 17738370 TI - ASSOCIATION OF AMIERICAN ANATOMISTS. PMID- 17738371 TI - AMERICAN MATHEMATICAL SOCIETY. PMID- 17738372 TI - THE NOMENCLATURE OF THE HYOID IN BIRDS. PMID- 17738373 TI - NOTES ON INORGANIC CHEMISTRY. PMID- 17738374 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17738375 TI - THE TEACHING OF MATHEMATICS FOR ENGINEERS. PMID- 17738376 TI - THE POINT OF VIEW IN TEACHING ENGINEERING MATHEMATICS. PMID- 17738377 TI - THE CHICAGO ACADEMY OF SCIENCES. PMID- 17738378 TI - LEHIGH UNIVERSITY AND THE UNIVERSITY OF LIVERPOOL. PMID- 17738379 TI - THE LLOYD LIBRARY AND MUSEUM. PMID- 17738380 TI - MEANING OF THE SPANISH WORD GAVILAN. PMID- 17738381 TI - THE ESSENTIAL MEANING OF D'ALEMBERT'S PRINCIPLE. PMID- 17738382 TI - SOME APPLE LEAF-SPOT FUNGI. PMID- 17738384 TI - COMMANDING OUR WEALTH. PMID- 17738383 TI - A CYCAD FROM THE UPPER CRETACEOUS IN MAVERICK COUNTY, TEXAS. PMID- 17738385 TI - EDWARD FRANKLIN GAINES. PMID- 17738386 TI - ASTRONOMY IN SOVIET RUSSIA. PMID- 17738387 TI - THE REORGANIZATION OF THE OFFICE OF THE SURGEON GENERAL. PMID- 17738388 TI - A TECTONIC MAP OF THE UNITED STATES. PMID- 17738389 TI - MORE ABOUT COOPERATIVE STUDIES IN HUMAN BIOLOGY. PMID- 17738390 TI - F2 AND N1-METHYLNICOTINAMIDE. PMID- 17738391 TI - AGE AT STARRING IN AMERICAN MEN OF SCIENCE. PMID- 17738392 TI - ASCORBIC AND DEHYDROASCORBIC ACID IN COOKED GARDEN BEETS. PMID- 17738393 TI - THE EFFECT OF BIOTIN ON THE METABOLISM OF LIVER SLICES FROM BIOTINDEFICIENT RATS. PMID- 17738394 TI - 10-NOR-PROGESTERONE, A PHYSIOLOGICALLY ACTIVE LOWER HOMOLOG OF PROGESTERONE. PMID- 17738395 TI - APPARATUS FOR THE USE OF SOLID CARBON DIOXIDE AS A SOURCE OF CO2 GAS. PMID- 17738396 TI - Radioactive wastes. PMID- 17738398 TI - The emergence of ecology as a new integrative discipline. PMID- 17738397 TI - The fertilizer-ozone connection. PMID- 17738399 TI - West valley: the question is where does buck stop on nuclear wastes? PMID- 17738400 TI - Donald kennedy to head FDA. PMID- 17738401 TI - Alaskan gas: impact of pipeline on canadian north stirs a debate. PMID- 17738402 TI - Demise of military med school likely. PMID- 17738403 TI - Berger commission brings the north to the South. PMID- 17738404 TI - Nuclear power plants: why do some work better than others? PMID- 17738405 TI - Ion cyclotron resonance: fourier transform mass spectrometry. PMID- 17738406 TI - The pittsburgh conference: a special instrumentation report. PMID- 17738407 TI - Smart instruments: microprocessors not the whole story. PMID- 17738408 TI - Coping with the high cost of instruments. PMID- 17738410 TI - Clan and land. PMID- 17738409 TI - Farming communities and the demands of archeology. PMID- 17738411 TI - Psychological theory. PMID- 17738413 TI - Composites. PMID- 17738412 TI - Solution chemistry. PMID- 17738414 TI - South american geochronology: radiometric time scale for middle to late tertiary mammal-bearing horizons in patagonia. AB - Radiometric (potassium-argon) age determinations for basalts and tuffs associated with middle to late Tertiary mammal-bearing horizons in Patagonia, southern Argentina, permit refinement of boundaries and hiatuses between beds of Deseadan (early Oligocene) through Friasian (middle to late Miocene) age. At two localities beds of Deseadan age are overlain by basalts, which gave dates of 33.6 and 35.4 million years ago; 34.0 million years ago is tentatively accepted as a terminal date for known Deseadan. At several localities beds of Colhuehuapian age are underlain by basalts, which gave dates ranging from 28.8 to 24.3 million years ago; 25.0 million years is tentatively taken as a basal age for known Colhuehuapian. The paleontological hiatus between known Deseadan and known Colhuehuapian is thus in the order of 9.0 million years. Two tuffs from the Santa Cruz Formation (Santacrucian) gave ages of 21.7 and 18.5 million years. Plagioclase and biotite concentrates of an ignimbrite from the Collon Cura Formation (Friasian) gave ages ranging from 15.4 to 14.0 million years. PMID- 17738415 TI - Teeth in ichthyornis (class: aves). AB - Both Hesperornis and Ichthyornis are toothed birds; they and Archaeopteryx share broad flattened teeth with highly expanded roots. The teeth of Ichthyornis have been reported to have been set in sockets as were those of Archaeopteryx, but new specimens of Ichthyornis show the teeth set in a groove as in Hesperornis. These new fossils are from an adult but not old bird; thus, the presence or absence of tooth sockets in birds may be dependent on age. PMID- 17738416 TI - Isoleucine epimerization for dating marine sediments: importance of analyzing monospecific foraminiferal samples. AB - The rate of isoleucine epimerization in fossil planktonic foraminifera is strongly species-dependent. Alloisoleucine/isoleucine ratios of two species of the same age can vary by more than a factor of 2. This finding, in combination with the known temporal and spatial variability of foraminiferal assemblages, demonstrates the critical importance of basing geochronological studies of marine sediments on monospecific samples. One rapidly epimerizing species generates a calibration curve of potentially high precision for dating sediments between the ages of about 50,000 to 400,000 years. PMID- 17738417 TI - Sunlight-induced bromate formation in chlorinated seawater. AB - Chlorinated waters are being introduced into estuarine and coastal areas in increasing quantities. In such systems, the chlorine reacts with the natural bromide and ammonia to produce the highly toxic hypobromous acid, hypobromite ion, and haloamines. Sunlight causes up to 50 percent conversion to bromate ion, which is persistent in natural waters and has an unknown toxicity. PMID- 17738418 TI - Triacontanol: a new naturally occurring plant growth regulator. AB - Alfalfa meal and chloroform extracts of the meal have increased the growth and yield of several plant species. A crystalline substance isolated from the active fraction of alfalfa meal increased the dry weight and water uptake of rice seedlings when sprayed on the foliage or applied in nutrient culture. The substance was identified as triacontanol by mass spectrometry. Sprays containing this compound also increased the growth of corn, and barley grown in soil. Authentic triacontanol produced a similar response over a wide range of concentrations on rice grown in nutrient cultures and tomatoes grown in soil. PMID- 17738419 TI - Regional specialization of reptilian scale surfaces: relation of texture and biologic role. AB - The iridescent body scales of the fossorial uropeltid snakes produce these interference colors by keratinous ridges spaced at 2500 A. The pattern inhibits wetting of the surface and adhesion of soil particles and thus reduces friction between the snake's trunk and walls of its tunnel. The epidermal scales of the blunt tail show a sharply defined pattern of spines and ridges with convergent flutings. Dirt caught here forms a plug that protects the snake's caudal end. The sharp transition of surface textures suggests (i) that selection for each of the two roles is great, and (ii) that the interference colors of many fossorial snakes indicate that friction as well as dirt adhesion are being reduced. PMID- 17738421 TI - PRODUCTS and MATERIALS. PMID- 17738420 TI - Nitrogen fixation in grass-spirillum systems. PMID- 17738422 TI - Man and the biosphere. PMID- 17738423 TI - Overpopulation. PMID- 17738424 TI - Antiwar statement. PMID- 17738425 TI - Letter to the editor. PMID- 17738426 TI - Science for nonscientists. PMID- 17738427 TI - Making Faces across the Gulf.. PMID- 17738429 TI - Relevance of particle accelerators to national goals. PMID- 17738428 TI - The beginnings of experimental petrology. AB - Van't Hoff's work constitutes the first systematic contribution to experimental petrology. At all times, the problem was perceived as geologic in nature and the laboratory results were checked against natural assemblages whenever possible. The phase rule was not used, nor, for that matter, was chemical thermodynamics, except for the Van't Hoff equation. However, the work of Van't Hoff and Van Deventer was indirectly involved in the evolution of phase theory by Roozeboom, Van Rijn van Alkemade, and Schreinemakers. Meyerhoffer himself wrote the first text explicitly devoted to the phase rule. The impact of Van't Hoff's study was enormous, but it was restricted to those geologists willing and able to cope with chemistry. Foremost among them were igneous petrologists who had long since accepted chemical arguments for classification purposes. I consider the Geophysical Laboratory program to be the most direct heir of the Van't Hoff approach. Although the shape of that program was formulated independently by Van Hise, Becker, Day, and others, the inspiration they derived from Van't Hoff's successes is clearly acknowledged. The study of the fusion of plagioclases by Day and Allen (41), which directly led to the authorization for the Geophysical Laboratory, was the igneous counterpart of Van't Hoff's low-temperature experimental petrology. On metamorphic petrology, too, Van't Hoff left his mark, with V. M. Goldschmidt acting as his disciple. The interpretation of the Kristiania contact rocks was explicitly based on Van't Hoff's double salt law in preference to the phase rule. Sedimentologists remained unaffected and continued their preoccupation with description and classification. Chemical arguments remained subordinate in their work and of an elementary nature, underscoring the chasm between "hard" rocks and "soft" rocks. This gulf is only now beginning to close as a result of the blossoming of experimental petrology and geochemistry since World War II. At last the generality of the point of view of Gibbs is being accepted. If Van't Hoff's contribution had been appreciated fully at the time, this could have happened 70 years earlier. PMID- 17738430 TI - The Economist's Approach to Pollution and Its Control. PMID- 17738431 TI - Addict treatment programs. PMID- 17738432 TI - Tools for archeology: AIDS to studying the past. PMID- 17738433 TI - Reduction of stratospheric ozone by nitrogen oxide catalysts from supersonic transport exhaust. AB - Although a great deal of attention has been given to the role of water vapor from supersonic transport (SST) exhaust in the stratosphere, oxides of nitrogen from SST exhaust pose a much greater threat to the ozone shield than does an increase in water. The projected increase in stratospheric oxides of nitrogen could reduce the ozone shield by about a factor of 2, thus permitting the harsh radiation below 300 nanometers to permeate the lower atmosphere. PMID- 17738434 TI - Apples in a spacecraft. AB - Some consequences of Newtonian mechanics, previously overlooked, result in a new understanding of the behavior of small bodies in the solar system. Collisions between such bodies lead not to a scattering of these bodies over an increasing volume but instead to a contraction resulting in a "jet stream," with application to meteor streams and streams of asteroids. It is possible that comets are formed by bunching in such streams. PMID- 17738435 TI - Rapidly changing radio images. AB - Differences in total transit time can give rise to images that expand at arbitrarily high speed. Two versions of a model based on this idea can account for the varying microwave structure reported for the quasar 3C 279. Other possible examples are suggested. PMID- 17738436 TI - Gulf stream and middle atlantic bight: complex thermal structure as seen from an environmental satellite. AB - High-resolution infrared imagery from the ITOS 1 satellite demonstrates the utility of synoptic sea-surface temperature information. The northern edge of the Gulf Stream, the slope waters, and the shelf waters display complex thermal characteristics with distinct temperature gradients separating these three water masses. This type of information can be very useful for increasing our understanding of many physical phenomena that occur over Earth's oceans. PMID- 17738437 TI - Rifting in iceland: new geodetic data. AB - Small but measurable lengthening of several survey lines within the eastern rift zone of Iceland occurred between 1967 and 1970. The changes can be interpreted as a widening of the rift by 6 to 7 centimeters, possibly during the 1970 eruption of Hekla volcano. PMID- 17738438 TI - Quartz: synthesis at Earth-surface conditions. AB - Quartz has been crystallized directly from seawater at room temperature. This is the first time that identifiable quartz has been synthesized in aqueous solution at earth-surface conditions without the aging of an original amorphous precipitate. The concentration of dissolved silica in equilibrium with quartz at 20 degrees C and 1 atmosphere is 4.4+/-0.3 parts per million, a value in agreement with the theoretical value obtained by a constant heat capacity fit of higher temperature equilibrium data. This experiment confirms the results of petrologic investigations which suggest that quartz precipitates directly from aqueous solution during chemical weathering and early diagenesis. PMID- 17738439 TI - Ultrahigh-frequency electromagnetic fields for weed control: phytotoxicity and selectivity. AB - An ultrahigh-frequency electromagnetic field (2450+/-20 megahertz) is lethal to plants and seeds of several species after relatively short exposure times. Some species are highly susceptible; others are relatively resistant to a given field intensity. Phytotoxicity is increased in imbibed seeds and young plants. It is decreased in dry seeds and sometimes decreased in mature plants. Soil partially attenuates the field but is not opaque to it. PMID- 17738440 TI - Relation of sunspot and earthquake activity. PMID- 17738441 TI - Flux of micrometeoroids: lunar sample analyses compared with flux model. PMID- 17738442 TI - SECTION E-GEOLOGY AND GEOGRAPHY. PMID- 17738444 TI - THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE AND SCIENTIFIC ORGANIZATION. PMID- 17738443 TI - ZOOLOGICAL AIMS AND OPPORTUNITIES. PMID- 17738445 TI - AN UNCOMMON ICE FORMATION. PMID- 17738447 TI - CELLULOID LANTERN SLIDES. PMID- 17738446 TI - HOLDING LARGE SPECIMENS FOR DISSECTION. PMID- 17738448 TI - REPORT OF THE TREASURER FOR 1918. PMID- 17738449 TI - A METHOD OF DEMONSTRATING THE DIFFERENCE-TONES. PMID- 17738450 TI - SECTION H-ANTHROPOLOGY AND PSYCHOLOGY. PMID- 17738451 TI - THE SOCIETY OF AMERICAN FORESTERS. PMID- 17738452 TI - PROBLEMS, METHODS AND RESULTS IN BEHAVIOR. PMID- 17738453 TI - GEORGE JENNINGS HINDE. PMID- 17738454 TI - INQUIRY OF THE AMERICAN GEOGRAPHICAL SOCIETY FOR THE INFORMATION OF THE PEACE COMMISSIONERS. PMID- 17738456 TI - EXPERIMENTAL OSMOSIS WITH A LIVING MEMBRANE. PMID- 17738455 TI - A LEAGUE OF NATIONS. PMID- 17738457 TI - QUOTATIONS. PMID- 17738459 TI - TMI Public Health Fund. PMID- 17738458 TI - SPECIAL ARTICLES. PMID- 17738460 TI - TMI Public Health Fund. PMID- 17738461 TI - Software piracy. PMID- 17738462 TI - Instruction in science and mathematics. PMID- 17738463 TI - TMI Public Health Fund. PMID- 17738465 TI - The 1983 nobel prize in physics. PMID- 17738464 TI - Carbon dioxide emissions. PMID- 17738466 TI - From teosinte to maize: the catastrophic sexual transmutation. AB - An alternative to the theory that the ear of maize (Zea mays ssp. mays) evolved from a slender female ear of a Mexican annual teosinte holds that it was derived from the central spike of a male teosinte inflorescence (tassel) which terminates the primary lateral branches. This alternative hypothesis is more consistent with morphology and explains the anomalous lack of significant genetic and biochemical differences between these taxa. Maize, the only cereal with unisexual inflorescences, evolved through a sudden epigenetic sexual transmutation involving condensation of primary branches, which brought their tassels into the zone of female expression, leading to strong apical dominance and a catastrophic shift in nutrient allocation. Initially, this quantum change may have involved no new mutations, but rather genetic assimilation under human selection of an abnormality, perhaps environmentally triggered. PMID- 17738467 TI - Star Wars Plan Gets a Green Light: A White House policy group, acting on the advice of two scientific panels, has recommended a major missile defense program. PMID- 17738468 TI - Businessmen urge major cuts in federal R & d. PMID- 17738469 TI - Cambridge voters turn down weapons ban. PMID- 17738470 TI - Kangaroos defended. PMID- 17738471 TI - Agrigenetics to go public. PMID- 17738472 TI - To Catch a Spy: The FBI's tactics in arresting an East German physicist at a meeting of the American Vacuum Society have raised some ire. PMID- 17738473 TI - NAE Seeks a Share of the Limelight: The Engineering Academy, with a renewed focus on technology and society, wants a more prominent role in the policy arena. PMID- 17738474 TI - IRAS Science Briefings. PMID- 17738475 TI - Harbingers of the Coalinga Earthquake: An encircling pattern of earthquakes preceded the damaging shock near Coalinga, suggesting how some earthquakes might be anticipated. PMID- 17738476 TI - aaas Annual Meeting New York 24-29 May 1984. PMID- 17738477 TI - Variability in the tropics: the ecology of a tropical forest. PMID- 17738478 TI - Reproductive behavior: mate choice. PMID- 17738479 TI - The planet venus: venus. PMID- 17738480 TI - The plasma state: physics of ion-ion and electron-ion collisions. PMID- 17738481 TI - Precambrian geology: geological evolution of the Earth during the precambrian. PMID- 17738482 TI - Chlorine-36 dating of saline sediments: preliminary results from searles lake, california. AB - Measurements have been made of the ratios of chlorine-36 to chlorine in five halite samples from Searles Lake sediments, previously dated by carbon-14, thorium-230, and magnetostratigraphic techniques. The ages calculated from the chlorine ratios are generally concordant with those from the other methods, implying the constancy of the chlorine input ratio over the last million years. PMID- 17738483 TI - Full Circule. PMID- 17738484 TI - Inductive Inference: A New Approach. PMID- 17738486 TI - News of Science. PMID- 17738485 TI - Robert H. Lowie, Anthropologist. PMID- 17738487 TI - Isolation of Cytoplasmic Particles with Cytochrome Oxidase Activity from Apples. PMID- 17738488 TI - Alteration of Clay Minerals by Digestive Processes of Marine Organisms. PMID- 17738489 TI - Meetings and Societies. PMID- 17738491 TI - TRENDS OF MODERN BIOLOGY. PMID- 17738490 TI - EQUIPMENT NEWS. PMID- 17738492 TI - EARTH-CURRENT OBSERVATIONS. PMID- 17738493 TI - COLLABORATORS IN THE STANDARDIZATION OF BIOLOGICAL STAINS. PMID- 17738494 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17738495 TI - A CHEMICAL SPELLING MATCH. PMID- 17738496 TI - TINGITIDAe OR TINGIDAe. PMID- 17738497 TI - RELATIVITY. PMID- 17738498 TI - MUSCINA PASCUORUM MEIGEN IN NEW ENGLAND. PMID- 17738499 TI - PROOF OF THE POWER OF THE WHEAT PLANT TO FIX ATMOSPHERIC NITROGEN. PMID- 17738500 TI - THE AMERICAN CHEMICAL SOCIETY. PMID- 17738501 TI - THE STRUCTURE OF THE UNIVERSE. PMID- 17738502 TI - BLOOD PARASITES. PMID- 17738503 TI - SOME EDUCATIONAL PROBLEMS IN KANSAS. PMID- 17738504 TI - THE AMERICAN SOCIETY OF NATURALISTS. PMID- 17738505 TI - THE AMERICAN PSYCHOLOGICAL ASSOCIATION. PMID- 17738506 TI - THE DANA CENTENARY. PMID- 17738507 TI - ATOMIC IONIZATION AND ATOMIC CHARGES. PMID- 17738508 TI - PROFESSOR NOGUCHI'S RESEARCHES ON INFECTIVE DISEASES. PMID- 17738509 TI - DIATOM COLLECTION OF THE UNITED STATES NATIONAL MUSEUM. PMID- 17738510 TI - REVERSIBILITY IN ARTIFICIAL PARTHENOGENESIS. PMID- 17738511 TI - Scientific Manpower. PMID- 17738512 TI - The mystery of the shroud. PMID- 17738513 TI - The mystery of the shroud. PMID- 17738514 TI - The mystery of the shroud. PMID- 17738515 TI - The mystery of the shroud. PMID- 17738517 TI - The mystery of the shroud. PMID- 17738516 TI - The mystery of the shroud. PMID- 17738518 TI - Five years of energy paralysis. PMID- 17738519 TI - Time, structure, and fluctuations. AB - Fundamental conceptual problems that arise from the macroscopic and microscopic aspects of the second law of thermodynamics are considered. It is shown that nonequilibrium may become a source of order and that irreversible processes may lead to a new type of dynamic states of matter called "dissipative structures." The thermodynamic theory of such structures is outlined. A microscopic definition of irreversible processes is given, and a transformation theory is developed that allows one to introduce nonunitary equations of motion that explicitly display irreversibility and approach to thermodynamic equilibrium. The work of the group at the University of Brussels in these fields is briefly reviewed. In this new development of theoretical chemistry and physics, it is likely that thermodynamic concepts will play an ever-increasing role. PMID- 17738521 TI - We Wanted to Cut and, Well, um, There It Was. PMID- 17738520 TI - Report of fusion breakthrough proves to be a media event. PMID- 17738522 TI - Clash in Congress over the Honourable Schoolboy. PMID- 17738523 TI - Waiting for the other plate to drop in california. PMID- 17738524 TI - Microcomputers: the great electronic mouse race. PMID- 17738525 TI - 1978-79 AAAS Congressional Science Fellows Selected. PMID- 17738527 TI - Proposals and resolutions invited for 1979 council meeting. PMID- 17738526 TI - OCEANS '78 Set for Washington, D.C. PMID- 17738528 TI - Endangered primates. PMID- 17738529 TI - Perceptual modes. PMID- 17738530 TI - Brain biochemistry. PMID- 17738531 TI - The paredon, Mexico, obsidian source and early formative exchange. AB - In 1975, archeological surface surveys of trade routes located again a pre Hispanic obsidian source in central Mexico first reported in 1902. Initial trace element studies of the Paredon source through an analysis by neutron activation have been compared with similar studies of the obsidian found at Chalcatzingo 150 kilometers from the source. These comparisons indicate that obsidian from Paredon, rather than Otumba, was of primary importance during the Early Formative in central Mexico. PMID- 17738532 TI - Amorphous ice on saturnian rings and on icy satellites: its formation, stability, and observability. AB - Saturnian rings and icy satellites may be covered with amorphous rather than crystalline ice. Its likely source is water molecules sputtered by particles in the radiation belts, it may be stable, and its presence could be deduced from the rate of temperature drop in a shadow. Observation of this effect is, however, difficult, especially for the rings. A possible relation to the brightness anisotropy of ring A is pointed out. PMID- 17738533 TI - Deimos encounter by viking: preliminary imaging results. AB - Recent close flybys of Deimos by Viking revealed a smooth-appearing surface void of grooves. Higher-resolution pictures showed that the surface was actually covered with craters but that a regolith filled the smaller craters, giving the smooth appearance. The surface was also covered with boulders and bright streak like markings analogous to base-surge or ejecta cloud deposits. PMID- 17738534 TI - Earthquake Swarm Along the San Andreas Fault near Palmdale, Southern California, 1976 to 1977. AB - Between November 1976 and November 1977 a swarm of small earthquakes (local magnitude HS(-) + OH(-). This solid sulfur cathode was first used in a battery with an aluminum anode for an overall discharge reaction 2Al + 3S + 3OH( ) + 3H(2)O --> 2Al(OH)(3) + 3HS(-), giving a cell potential of 1.3 volts. The theoretical specific energy of the aluminum-sulfur battery (based on potassium salts) is 910 watt.hours per kilogram with an experimental specific energy of up to 220 watt.hours per kilogram. PMID- 17739626 TI - Photochemistry in the primitive solar nebula. PMID- 17739625 TI - Altered growth and cell walls in a fucose-deficient mutant of Arabidopsis. AB - A biochemical screening procedure was developed to identify mutants of Arabidopsis thaliana in which the polysaccharide composition of the cell wall was altered. Over 5000 ethyl methanesulfonate-mutagenized plants were analyzed by this method, leading to the identification of 38 mutant lines. One complementation group of mutants was completely deficient in l-fucose, a constituent of pectic and hemicellulosic polysaccharides. These mutant plants were dwarfed in growth habit, and their cell walls were considerably more fragile than normal. PMID- 17739627 TI - Photochemistry in the primitive solar nebula. PMID- 17739628 TI - Response. PMID- 17739629 TI - Subcultures in genetics. PMID- 17739630 TI - Mergings and divergings. PMID- 17739631 TI - Materials physics. PMID- 17739632 TI - Vignettes: chaos. PMID- 17739634 TI - Letter to the editor. PMID- 17739633 TI - Products & materials. PMID- 17739635 TI - Nomenclative etiquette. PMID- 17739636 TI - The supernatural department. PMID- 17739637 TI - Genetic technology and agricultural development. AB - The genetic technologies being adopted in South Asia are significant factors in the agricultural development of the area. But, labeling them " miracle seeds," solely responsible for recent agricultural growth, is misleading. Certainly the introduction of new genetic technology has catalyzed South Asian agriculture and has instilled a new dynamism essential to economic development. Somewhat similar phenomena have, however, been observed in other parts of the world in other periods of history. The nature of these genetic technologies, how they are being applied, and their limits and potential have been explored above. Also, the effects of these varieties on the generation of employment, and the distribution of benefits accruing from them have been examined in preliminary fashion. Stemming from the preceding discussion, two areas of priority appear obvious. First, the close association of genetic technologies with irrigation suggests that irrigation should receive more attention than it has in the past. Large scale public irrigation schemes are expensive and have tended to yield low rates of return. However, there appears to be room for marginal increases in, or improvements of, existing irrigation facilities. Second, even with a rapid spread of the practices associated with highyeild varieties, it may be too much to expect the farm sector to absorb the expected increases in the rural labor force. The generation of employment is a major problem in India as well as in most other developing countries. Hence, possibilities for expanding rural, nonfarm employment and controlling population growth should be sought vigorously. PMID- 17739638 TI - AAAS Names Five to Freedom Panel. PMID- 17739639 TI - Public interest: new group seeks redefinition of scientists' role. PMID- 17739640 TI - Plate Tectonics (II): Mountain Building and Continental Geology. PMID- 17739641 TI - Atmospheric carbon dioxide and aerosols: effects of large increases on global climate. AB - Effects on the global temperature of large increases in carbon dioxide and aerosol densities in the atmosphere of Earth have been computed. It is found that, although the addition of carbon dioxide in the atmosphere does increase the surface temperature, the rate of temperature increase diminishes with increasing carbon dioxide in the atmosphere. For aerosols, however, the net effect of increase in density is to reduce the surface temperature of Earth. Because of the exponential dependence of the backscattering, the rate of temperature decrease is augmented with increasing aerosol content. An increase by only a factor of 4 in global aerosol background concentration may be sufficient to reduce the surface temperature by as much as 3.5 degrees K. If sustained over a period of several years, such a temperature decrease over the whole globe is believed to be sufficient to trigger an ice age. PMID- 17739642 TI - Normal atmosphere: large radical and formaldehyde concentrations predicted. AB - A steady-state model of the normal (unpolluted) surface atmosphere predicts a daytime concentration of hydroxyl, hydroperoxyl, and methylperoxyl radicals approaching 5 x 10(8)molecules per cubic centimeter and a formaldehyde concentration of 5 x 10(10) molecules per cubic centimeter or 2 parts per billion. A radical chain reaction is proposed for the rapid removal of carbon monoxide, leading to a carbon monoxide lifetime as low as 0.2 year in the surface atmosphere. PMID- 17739643 TI - Informal contacts in science: a probabilistic model for communication processes. AB - Significant contacts among scientists within research specialties are generally infrequent and are distributed as an essentially random process, the pattern of most contacts conforming to a Poisson distribution. Extremely productive persons in a specialty, however, seem to form a separate distribution; they have a considerably higher number of contacts. PMID- 17739644 TI - Radio echo records cannot be used as evidence for convection in the antarctic ice sheet. PMID- 17739645 TI - Oxygen-18 studies of recent planktonic foraminifera. PMID- 17739646 TI - How did venus lose its angular momentum? PMID- 17739647 TI - Erratum. AB - In the article "Park is sought to save Indian tribe in Brazil" (News and Comment, 7 Dec. 1979, p. 1160), the University of Pennsylvania is given as the affiliation of Napoleon Chagnon. This is not correct. Chagnon is a member of the faculty of Pennsylvania State University. PMID- 17739648 TI - A modest basis for energy optimism. PMID- 17739649 TI - Ocean energy: forms and prospects. AB - The nature and distribution of power sources of the sea other than petroleum are discussed, along with possible entrees for their use. Waves, tides, currents, and salinity and temperature gradients all have the potential to contribute useful power. Submarine geothermal sources, salt domes, ice, and other marine-associated concentrations may be more important. There are opportunities to employ these marine power resources directly rather than for contributions to power grids or power-intensive products. Ancillary employment of the seawater as a coolant and of the sediments below the seabed for the disposal of nuclear wastes may be even more important uses than employment of the power that the sea contains. PMID- 17739650 TI - Western efficiency not welcome in Boston. PMID- 17739651 TI - Engineers form a new national association. PMID- 17739652 TI - For the 1980's, Beware All Expert Predictions. PMID- 17739654 TI - Venus: not simple or familiar, but interesting. PMID- 17739653 TI - Trade bans are hard weapons to use. PMID- 17739655 TI - Doing science in an inferno. PMID- 17739656 TI - Venus and Science's Fringe. PMID- 17739657 TI - The switch to evolutionism. PMID- 17739658 TI - Hunter-gatherer demography. PMID- 17739659 TI - An updating in petrology. PMID- 17739660 TI - Space research. PMID- 17739661 TI - Thermal evolution of plutons: a parameterized approach. AB - A conservation-of-energy equation has been derived for the spatially averaged magma temperature in a spherical pluton undergoing simultaneous crystallization and both internal (magma) and external (hydrothermal fluid) thermal convection. The model accounts for the dependence of magma viscosity on crystallinity, temperature, and bulk composition; it includes latent heat effects and the effects of different initial water concentrations in the melt and quantitatively considers the role that large volumes of circulatory hydrothermal fluids play in dissipating heat. The nonlinear ordinary differential equation describing these processes has been solved for a variety of magma compositions, initial termperatures, initial crystallinities, volume ratios of hydrothermal fluid to magma, and pluton sizes. These calculations are graphically summarized in plots of the average magma temperature versus time after emplacement. Solidification times, defined as the time necessary for magma to cool from the initial emplacement temperature to the solidus temperature vary as R(1,3), where R is the pluton radius. The solidification time of a pluton with a radius of 1 kilometer is 5 x 10(4) years; for an otherwise identical pluton with a radius of 10 kilometers, the solidification time is approximately 10(6) years. The water content has a marked effect on the solidification time. A granodiorite pluton with a radius of 5 kilometers and either 0.5 or 4 percent (by weight) water cools in 3.3 x 10(5) or 5 x 10(4) years, respectively. Convection solidification times are usually but not always less than conduction cooling times. PMID- 17739662 TI - Corotation Lag in Jupiter's Magnetosphere: Comparison of Observation and Theory. AB - Voyager 1 plasma flow data are compared with a recent theory that predicted measurable departures from rigid corotation in Jupiter's magnetosphere as a consequence of rapid plasma production and weak atmosphere-magnetosphere coupling. The comparison indicates that the theory can account for the observed corotation lag, provided that the plasma mass production rate during the Voyager 1 encounter was rather larger than expected, namely approximately 10(30) atomic mass units per second. PMID- 17739663 TI - Net energy analysis of alcohol production from sugarcane. AB - Energy requirements were calculated for the agricultural and the industrial phase of ethyl alcohol production from sugarcane grown in Louisiana. Agricultural energy requirements comprised 54 percent of all energy inputs, with machinery, fuel, and nitrogen fertilizer representing most of the energy subsidies. Overall net energy benefits (output:input) for alcohol production ranged from 1.8:1 to 0.9:1 depending on whether crop residues or fossil fuels were used for industrial processes. PMID- 17739665 TI - GROVE KARL GILBERT. PMID- 17739664 TI - Graphoglyptid burrows in modern deep-sea sediment. AB - The complex, highly patterned, invertebrate burrow systems known as "graphoglyptids" in ancient sedimentary rocks have now been recovered in box cores of modern deep-sea sediment. Spiroraphe, Cosmoraphe, and Paleodictyon occur as grooves in the tops of washed cores, and they apparently were produced and maintained as horizontal tunnel systems just a few millimeters below the sediment surface. These burrows, which are important as indicators of deepwater sedimentary environments in ancient strata, have been predicted in the modern deep sea but have not been found there until now. PMID- 17739666 TI - WAR BREAD. PMID- 17739668 TI - THE CRITERION OF SUBSPECIFIC INTERGRADATION IN VERTEBRATE ZOOLOGY. PMID- 17739667 TI - THE BOTANY AND PLANT PRODUCTS OF NORTHERN SOUTH AMERICA. PMID- 17739669 TI - COTTON AS A SEED CROP. PMID- 17739671 TI - THE ROCKEFELLER FOUNDATION. PMID- 17739670 TI - AN ASPECT OF THE RELATION BETWEEN ABUNDANCE, MIGRATION AND RANGE IN BIRDS. PMID- 17739672 TI - NOTE ON MEASURING THE RELATIVE RATES OF LIFE PROCESSES. PMID- 17739673 TI - HOW FOOD AND EXERCISE INCREASE OXIDATION IN THE BODY. PMID- 17739674 TI - THE AMERICAN TYPE OF UNIVERSITY. PMID- 17739676 TI - EVOLUTION THEORIES: STATIC, DETERMINANT, KINETIC. PMID- 17739675 TI - DR. EASTMAN'S RECENT PAPERS ON THE KINSHIP OF THE ARTHRODIRES. PMID- 17739677 TI - IONIZATION IN CLOSED VESSELS. PMID- 17739679 TI - ANHYDROUS SULPHOCYANIC ACID. PMID- 17739678 TI - LABORATORY APPARATUS FOR MEASUREMENT OF THE FORCE ON A CURRENT-CARRYING CONDUCTOR LYING IN A MAGNETIC FIELD. PMID- 17739680 TI - GEOLOGIC WORK ON THE COASTAL PLAIN. PMID- 17739681 TI - AN INTERNATIONAL COMMISSION ON SLEEPING SICKNESS. PMID- 17739682 TI - CINDER CONE NATIONAL MONUMENT. PMID- 17739683 TI - ADDRESS ON THE OCCASION OF THE DEDICATION OF THE LINNAeAN BRIDGE. PMID- 17739684 TI - THE INTERNATIONAL ASSOCIATION OF ACADEMIES. PMID- 17739685 TI - COMMENT AND CRITICISM. PMID- 17739686 TI - Crystallization of glucose in honey. PMID- 17739687 TI - The zero meridian of longitude. PMID- 17739688 TI - What's in a name? PMID- 17739689 TI - North-eastern and north-western Indian implements. PMID- 17739690 TI - Babirussa tusks from an Indian grave in British Columbia. PMID- 17739691 TI - Fish-remains in the North-American Silurian rocks. PMID- 17739692 TI - A muskrat with a round tail. PMID- 17739693 TI - SPECIALIZATION IN SCIENTIFIC STUDY. PMID- 17739694 TI - HIBERNATION OF THE LOWER VERTEBRATES. PMID- 17739695 TI - MERRIMAN'S METHOD OF LEAST SQUARES. PMID- 17739696 TI - TAIT'S HEAT. PMID- 17739697 TI - THE SOCIETY FOR PSYCHICAL RESEARCH. PMID- 17739698 TI - INTELLIGENCE FROM AMERICAN SCIENTIFIC STATIONS. PMID- 17739700 TI - Color Standards. PMID- 17739699 TI - Separating Pages of Publications. PMID- 17739701 TI - FACT AND THEORY IN SPECTROSCOPY. PMID- 17739702 TI - SOME PROBLEMS CONNECTED WITH DEEP MINING IN THE LAKE SUPERIOR COPPER DISTRICT. PMID- 17739703 TI - WHY HAS THE DOCTRINE OF LAISSEZ FAIRE BEEN ABANDONED? PMID- 17739704 TI - THE CARNEGIE FOUNDATION. PMID- 17739705 TI - THE ADVANCING MALASPINA GLACIER. PMID- 17739706 TI - IS THERE DETERMINATE VARIATION? PMID- 17739707 TI - Identification of commercial sources. PMID- 17739708 TI - Persecution of soviet scientists. PMID- 17739709 TI - Marketing the metric system. PMID- 17739710 TI - George Darwin's Father. PMID- 17739711 TI - Health records. PMID- 17739712 TI - The central role of chemistry. PMID- 17739713 TI - State-Selected Kinetics from Laser-Excited Fluorescence: Energy transfer and chemical reaction rates can be measured for individual molecular energy states. PMID- 17739715 TI - Military R & d: hard lessons of an electronic war. PMID- 17739714 TI - Cognitive Consequences of Formal and Informal Education: New accommodations are needed between school-based learning and learning experiences of everyday life. PMID- 17739716 TI - OTA Gets $2 Million. PMID- 17739717 TI - NASA and ESRO: A European Payload for the Space Shuttle. PMID- 17739718 TI - Court restores training money. PMID- 17739719 TI - An "understanding" on offshore oil. PMID- 17739721 TI - Microbiology: hazardous profession faces new uncertainties. PMID- 17739720 TI - Medical Devices: Should They Be Cleared before Marketing? PMID- 17739722 TI - The 1973 nobel prize for economic science. PMID- 17739723 TI - Science and technology: the next 50 years. PMID- 17739724 TI - Sulfur dioxide contributions to the atmosphere by volcanoes. AB - The first extensive measurements by remote-sensing correlation spectrometry of the sulfur dioxide emitted by volcanic plumes indicate that on the order of 10(3) metric tons of sulfur dioxide gas enter the atmosphere daily from Central American volcanoes. Extrapolation gives a minimum estimate of the annual amount of sulfur dioxide emitted from the world's volcanoes of about 10(7) metric tons. PMID- 17739725 TI - Radiometric ages of kodiak seamount and giacomini guyot, gulf of alaska: implications for circum-pacific tectonics. AB - Kodiak Seamount and Giacomini Guyot have been dated at 22.6 +/- 1.1 and 19.9 +/- 1.0 [2sigma (standard deviation)] x 10(6) years, respectively. Concordant whole rock and plagioclase potassium-argon dates and fission-track apatite ages demonstrate that significant quantities of excess radiogenic (40)Ar are not present in the dated samples. These seamounts are the northwesternmost edifices of the Pratt-Welker chain, which cuts obliquely across magnetic anomaly patterns in an older northeastern Pacific sea floor. The older of the two dated seamounts is in the Aleutian Trench, apparently about to be subducted. If one assumes that seamounts are generated by plate motion over a fixed hot spot in the mantle, a Pacific-plate motion of 6.6 centimeters per year during early Miocene time may be calculated. PMID- 17739726 TI - Earthquakes of strike-slip type in central california: evidence on the question of dilatancy. AB - The travel times of compressional waves from quarry explosions of well-known origin times, measured at the University of California network of seismographic stations for the period 1961 to the present, have been examined for evidence of premonitory changes prior to earthquakes of moderate magnitudes in the region. Velocities to seven station sites are generally constant to within +/- 1 percent, with occasional deviations of +/- 2 percent. Variations seem to bear no correlation to earthquake occurrence and are probably due to a combination of reading errors and changes in the source location within the quarry. PMID- 17739728 TI - Oceanic growth models. PMID- 17739727 TI - Cooperative tool use by captive hamadryas baboons. AB - A bonded pair of hamadryas baboons developed cooperative tool use without training. The male could get food with the tool but first had to get the tool from an adjoining cage which he could not enter. The female learned to give him the tool. Cooperation was temporarily disrupted by the terminal phase of the female's estrous inflation. PMID- 17739729 TI - Food additives: beneficial or deleterious? PMID- 17739731 TI - Galapagos symposium. PMID- 17739730 TI - To feed the world: what to do with changing climate. PMID- 17739732 TI - Food supply and the organic food myth. PMID- 17739733 TI - Computer assisted chemical research design. PMID- 17739734 TI - Geodynamics symposium in Mexico. PMID- 17739735 TI - Eye movement monitor. PMID- 17739736 TI - Microtome-cryostat. PMID- 17739737 TI - Ovens and incubators. PMID- 17739738 TI - Density gradient apparatus. PMID- 17739739 TI - Programmable calculator. PMID- 17739740 TI - Muscle pH Monitor. PMID- 17739741 TI - Portable pH Meter. PMID- 17739743 TI - Literature. PMID- 17739742 TI - Cell or tissue culture apparatus. PMID- 17739745 TI - Water baths. PMID- 17739744 TI - Urine refractometer-dispenser. PMID- 17739746 TI - Thermal analysis system. PMID- 17739748 TI - GENERAL EXAMINATIONS IN A MEDICAL SCHOOL: PLAN OF EXAMINATION RECENTLY ADOPTED AT HARVARD. PMID- 17739747 TI - THE CARNEGIE FOUNDATION FOR THE ADVANCEMENT OF TEACHING. PMID- 17739749 TI - HENRY WILSON SPANGLER. PMID- 17739751 TI - THOMAS HARRISON MONTGOMERY. PMID- 17739750 TI - DR. A. R. WALLACE AND THE UNIVERSITY OF COLORADO. PMID- 17739752 TI - THE USE OF THE WORD "GENOTYPE". PMID- 17739753 TI - UNIVERSITY REGISTRATION. PMID- 17739754 TI - THE TIDAL MACHINE. PMID- 17739755 TI - CONVOCATION WEEK MEETINGS. PMID- 17739756 TI - PLEISTOCENE MAN FROM IPSWICH (ENGLAND). PMID- 17739757 TI - THIRD LIST OF GENERIC NAMES FOR THE "OFFICIAL LIST OF ZOOLOGICAL NAMES". PMID- 17739759 TI - SECTION B--PHYSICS. PMID- 17739758 TI - ON THE ORIGIN OF A PINK-EYED GUINEA-PIG WITH COLORED COAT. PMID- 17739760 TI - JOHN LAWRENCE LECONTE. PMID- 17739762 TI - A NEW RULE FOR DIVISION IN ARITHMETIC. PMID- 17739761 TI - THE WEATHER IN OCTOBER, 1883. PMID- 17739763 TI - URNATELLA GRACILIS, A FRESH-WATER POLYZOAN. PMID- 17739765 TI - Radiant heat. PMID- 17739764 TI - THE PHYLOGENY OF THE HIGHER CRUSTACEA. PMID- 17739766 TI - Synchronism of geological formations. PMID- 17739767 TI - The Dora coal-field, Virginia. PMID- 17739768 TI - Area of a plane triangle. PMID- 17739769 TI - THOMSON AND TAIT'S NATURAL PHILOSOPHY.--II. PMID- 17739770 TI - INTELLIGENCE FROM AMERICAN SCIENTIFIC STATIONS. PMID- 17739771 TI - Instructions for contributors. PMID- 17739773 TI - Letters to the editor. PMID- 17739772 TI - Letters to the editor. PMID- 17739774 TI - More on amazonian fauna. PMID- 17739776 TI - Peace Research: SIPRI, in Sweden, Is Making a Role for Itself. PMID- 17739775 TI - Temperatures of the Earth's Upper Atmosphere. PMID- 17739777 TI - Investigation of horizon Beta. AB - Horizon beta is a subbottom reflector in the North Atlantic deep ocean sediments that extends over a large portion of the North America basin. Cores from an outcrop of beta contained shallow-water Aptian-Albian sediments and deep-water Cenomanian sediments. A core near an outcrop of a deeper horizon, horizon B, contained shallow-water Lower Cretaceous (Barremian-Hauterivian) sediments. These cores can be interpreted to support extensive subsidence of the eastern portion of the basin in early Cretaceous time. It is equally likely that the shallow water deposits are a result of sediments slumping into an already deep basin. A reconciliation of these interpretations depends upon the JOIDES project. PMID- 17739778 TI - Spores, pollen, and microplankton from the horizon Beta outcrop. AB - Palynology was used for dating a pre-Pleistocene deep-sea organic lutite layer situated stratigraphically near seismic horizon beta, below horizon A. The spores and pollen are closely identified, quantitatively, with nonmarine and marine Middle Cretaceous assemblages (Albian-Cenomanian) on the continents, an age designation that is confirmed by the occurrence of dinoflagellate cysts, acritarchs, foraminifers, and coccoliths in the investigated cores. The abundance of these well-preserved, land-derived assemblages in an area far removed from a source suggests some tectonic displacement since their deposition. PMID- 17739779 TI - Pulsating Radio Sources near the Crab Nebula. AB - Two new pulsating radio sources, designated NP 0527 and NP 0532, were found near the Crab Nebula and could be coincident with it. Both sources are sporadic, and no periodicities are evident. The pulse dispersions indicate that 1.58 +/- 0.03 and 1.74 +/- 0.02 x 10(20) electrons per square centimeter lie in the direction of NP 0527 and NP 0532, respectively. PMID- 17739780 TI - Surface structure of polymers: glancing-angle electron diffraction study of polyethylene. AB - The surface regions of polyethylene nucleated and crystallized in contact with both a high-energy surface (gold) and a low-energy surface (fluorinated ethylene propylene copolymer Teflon) have been examined by means of glancing-angle electron-diffraction techniques. Examination of these surfaces has been confined to a maximum depth of 120 angstroms. The surface region of the polyethylene generated in contact with the gold is considerably more crystalline than the surface generated in contact with the fluorinated ethylene-propylene copolymer Teflon. These results tend to corroborate recent wettability and infrared studies. Apparently, the surface structure of polyethylene is highly dependent upon the method of preparation. PMID- 17739781 TI - Amino Acid composition of organic matrix in calcareous oolites. AB - Examination of the organic matter in some modern and fossil oolites has shown that it contains protein, with a high content of acidic amino acids. Artificial oolites from a water-processing plant contained no amino acids. The protein matrix may influence the formation of natural oolites by concentrating calcium ions. PMID- 17739782 TI - Potassium feldspar in weekeroo station, kodaikanal, and colomera iron meteorites. PMID- 17739784 TI - Instrumentation. PMID- 17739783 TI - This week in science. PMID- 17739785 TI - Response. PMID- 17739786 TI - Sciencescope. PMID- 17739787 TI - NASA PR: Hype or Public Education? PMID- 17739789 TI - The biggest shake-up for british science in 30 years. PMID- 17739788 TI - Calculator adds up the dollars. PMID- 17739790 TI - Good to take top commerce post. PMID- 17739791 TI - SSC Deathwatch Starts Again. PMID- 17739792 TI - One climber got there first. PMID- 17739793 TI - Between a rock and a liquid place. PMID- 17739794 TI - Galaxies in collision-up close. PMID- 17739795 TI - Comeback for karisoke. PMID- 17739796 TI - Zoologist found guilty on smuggling count. PMID- 17739797 TI - Congress Passes Broad NIH Bill. PMID- 17739798 TI - Biotech Firm Holes Up at MBL. PMID- 17739799 TI - Dark matter and the equivalence principle. PMID- 17739800 TI - Gas-phase ion chromatography: transition metal state selection and carbon cluster formation. AB - Gas-phase ion chromatography can separate ions that have the same mass but differ in isomeric structure or electronic configuration. The main features of this technique are briefly outlined, and applications to a series of problems in transition metal chemistry and carbon cluster chemistry are described. Examples in transition metal chemistry include state-selective reactivity, excited state deactivation, and state-selective ligand binding energies. For clusters, ion chromatography was used to determine the structure of pure carbon cluster ions as a function of size from C(4) to C(84). The results indicate that carbon grows first in linear chains, transforms to monocyclic planar rings at about C(10), and forms new families of planar bi-, tri-, and tetracyclic rings at C(20), C(30), and C(40), respectively. Fullerenes, which mysteriously appear at C(30) and dominate by C(50), are generated by heating the planar ring systems above an isomerization barrier rather than by growth of graphite precursors. PMID- 17739801 TI - True atomic resolution by atomic force microscopy through repulsive and attractive forces. AB - The (1014) cleavage plane of calcite has been investigated by atomic force microscopy in water at room temperature. True lateral atomic-scale resolution was achieved; the atomic-scale periodicities as well as the expected relative positions of the atoms within each unit cell were obtained. Along monoatomic step lines, atomic-scale kinks, representing point-like defects, were resolved. Attractive forces on the order of 10(-11) newton acting between single atomic sites on the sample and the front atoms of the tip were directly measured and provided the highest, most reliable resolution on a flat, well-ordered surface. PMID- 17739802 TI - High-resolution and analytical transmission electron microscopy of mineral disorder and reactions. AB - Crystal defects and chemical reactions occurring at scales beyond the resolution of light microscopes have major effects on the chemical and physical properties of rocks and minerals. High-resolution imaging, diffraction, and chemical analysis in the transmission electron microscope have become important methods for exploring mineral defect structures and reaction mechanisms and for studying the distribution of phases resulting from reactions. These techniques have shown that structural disorder is common in some rock-forming minerals but rare in others. They have also established mechanisms by which many reactions occur at the atomic cluster scale. These data thus provide an atomistic basis for understanding the kinetics of geological reactions. Furthermore, apparent major element, minor-element, and trace-element chemistry of minerals can be influenced by submicroscopic inclusions or intergrowths, which commonly form as products of solid-state reactions. PMID- 17739804 TI - Sound velocities in olivine at Earth mantle pressures. AB - The independent elastic constants of an upper mantle mineral, San Carlos olivine [(Mg(1.8)Fe(0.2))SiO(4)], were measured from 0 to 12.5 gigapascals. Evidence is offered in support of the proposition that the explicit temperature dependence of the bulk modulus is small over the range of temperatures and pressures thought to prevail above the 400-kilometer discontinuity, and thus the data can be extrapolated to estimate the properties of olivine under mantle conditions at a depth of 400 kilometers. In the absence of high-temperature data at high pressures, estimates are made of the properties of olivine under mantle conditions to a depth of 400 kilometers. In contrast with low-pressure laboratory data, the predicted covariance of shear and compressional velocities as a function of temperature nearly matches the seismically estimated value for the lower mantle. PMID- 17739803 TI - Atmosphere-surface exchange measurements. AB - The exchange of various trace species and energy at the earth's surface plays an important role in climate, ecology, and human health and welfare. Surface exchange measurements can be difficult to obtain yet are important to understand physical processes, assess environmental and global change impacts, and develop robust parameterizations of atmospheric processes. The physics and turbulent structure of the atmospheric boundary layer are reviewed as they contribute to dry surface exchange rates (fluxes). Micrometeorological, budget, and enclosure techniques used to measure or estimate surface fluxes are described, along with their respective advantages and limitations. Various measurement issues (such as site characteristics, sampling considerations, sensor attributes, and flow distortion) impact on the ability to obtain representative surface-based and airborne flux data. PMID- 17739805 TI - Direct imaging of the diacetylene solid-state monomer-polymer phase transformation. AB - The solid-state phase transformation from 1,6-di(N-carbazolyl)-2-4-hexadiyne (DCHD) diacetylene monomer to polymer has been studied dynamically by low-dose selected area electron diffraction and high-resolution electron microscopy. The total exposure required to induce polymerization is five orders of magnitude smaller than the critical dose for electron beam damage. The phase transformation is quasi-homogeneous, with the lattice parameters changing continuously as a function of beam dose. Characteristic streaking that develops in the selected area electron diffraction patterns in the [200] reciprocal directions during the intermediate stages of the transformation provides information about the defect mediated mechanisms of this reaction. PMID- 17739807 TI - Response. PMID- 17739806 TI - Poly(phenylcarbyne): A Polymer Precursor to Diamond-Like Carbon. AB - The synthesis of poly(phenylcarbyne), one of a class of carbon-based random network polymers, is reported. The network backbone of this polymer is composed of tetrahedrally hybridized carbon atoms, each bearing one phenyl substituent and linking, by means of three carbon-carbon single bonds, into a three-dimensional random network of fused rings. This atomic-level carbon network backbone confers unusual properties on the polymer, including facile thermal decomposition, which yields diamond or diamond-like carbon phases at atmospheric pressure. PMID- 17739808 TI - Metal-metal bonds in bimetallic surfaces. PMID- 17739810 TI - Chemistry of the cosmos. PMID- 17739809 TI - Final theory in biology. PMID- 17739811 TI - Cell measurement. PMID- 17739813 TI - Swine flu: quantifying the "possibility". PMID- 17739812 TI - Products & materials. PMID- 17739814 TI - Energy conservation and credibility. PMID- 17739815 TI - PBB Incident. PMID- 17739816 TI - Moral periodic table. PMID- 17739817 TI - Antiviral agent: abbott tests. PMID- 17739819 TI - The shape of the Earth. PMID- 17739818 TI - More laws, more complexity. PMID- 17739820 TI - The arctic mirage and the early north atlantic. AB - The arctic mirage is a phenomenon that is common in higher latitudes. It occurs under conditions of pronounced temperature inversion, which impart to the air a refractive capability that may equal or exceed the curvature of the earth. Manifestations of the arctic mirage, though largely forgotten in modern times, are described in the earliest accounts of North Atlantic discovery. This interdisciplinary investigation, combining historical induction with scientific observation and analysis, has suggested a new interpretation of historical events. We believe that information gleaned from these mirages was vital to Norse navigation and exploration in the North Atlantic. We further contend that the mirage may furnish a logical basis for the pervasive ancient and medieval concept of the flat or saucer-shaped world. PMID- 17739821 TI - Energy conservation in new housing design. PMID- 17739822 TI - Reactor safety: congress hears critics of rasmussen report. PMID- 17739823 TI - Glomar Explorer: CIA's Salvage Ship a Giant Leap in Ocean Engineering. PMID- 17739824 TI - Currie inquiry puts pentagon research job under cloud. PMID- 17739825 TI - Nuclear initiative: californians vote "no," but legislature acts. PMID- 17739826 TI - Plague incidence up in u.s. PMID- 17739827 TI - Center for short-lived phenomena spins off. PMID- 17739828 TI - National medal of science winners. PMID- 17739830 TI - Dream cycles. PMID- 17739829 TI - Fusion research (I): what is the program buying the country? PMID- 17739831 TI - Laser spectroscopy: illuminating the dynamics of collisions. PMID- 17739833 TI - Regulatory enzymes. PMID- 17739832 TI - Norms of reward. PMID- 17739834 TI - Track etching. PMID- 17739835 TI - Physical adsorption. PMID- 17739837 TI - Size variations in planktonic foraminifera: implications for quantitative paleoclimatic analysis. AB - Populations of planktonic foraminiferal species and phenotypes, distinguished on the basis of color and coiling direction, reach maximum average test sizes in their regions of optimum development. Therefore, tropical species are largest in tropical waters, while polar species are largest in polar waters. Species living in subtropical and subpolar waters decrease in test size with both increasing and decreasing temperature. PMID- 17739836 TI - N-nitroso compounds: detection in ambient air. AB - By use of a new, highly selective detection technique for N-nitroso compounds, which is sensitive to picogram quantities and which is based on the catalytic cleavage of the N-NO bond and the subsequent detection of the nitrosyl radical, dimethylnitrosamine has been found in concentrations of 0.02 to 0.96 part per billion in three out of five air samples from Baltimore, Maryland, and 0.014 to 0.051 part per billion in five out of six air samples from Belle, West Virginia. The sensitivity of the analytical procedures used was 1 part in 10(12). The presence of dimethylnitrosamine has been confirmed by using the new detector in conjunction with both a gas-liquid chromatograph and a high-performance liquid chromatograph. In addition, between one and three as yet unidentified N-nitroso compounds were detected in both cities. N-Nitroso compounds were not found in air samples from Philadelphia, Pennsylvania; Wilmington, Delaware; and Waltham, Massachusetts. PMID- 17739839 TI - Properties of the background global aerosol and their effects on climate. AB - Properties of the aerosols above Hawaii, Alaska, and the South Pole are derived from sun photometry at several wavelengths. The mass loading of aerosol material is several milligrams per square meter. At the South Pole the mean particle radius is 0.04 micrometer; at Hawaii in March 1975 there was a thin volcanic layer with a mean particle radius of 0.1 micrometer. The aerosols cause heating of the earth-atmosphere system at the poles and cooling at low latitudes. PMID- 17739838 TI - Enhancement of algal growth and productivity by grazing zooplankton. AB - Colonies of the common planktonic green alga, Sphaerocystis schroeteri, are only partially disrupted and assimilated by Daphnia magna, a natural predator. The Daphnia break up the outer protective gelatinous sheath that surrounds Sphaerocystis colonies, but most of the algal cells emerge from Daphnia guts intact and in viable condition. During gut passage, these viable cells take up nutrients, such as phosphorus, both from algal remains and from Daphnia metabolites. This nutrient supply stimulates algal carbon fixation and cell division. Enhanced algal growth, observed after gut passage, can compensate for the minor losses to the population caused by grazing. Nutrients regenerated by grazers may produce the summer bloom of gelatinous green algae during the seasonal succession of lake phytoplankton. PMID- 17739840 TI - Metamict mineral alteration: an implication for radioactive waste disposal. AB - Pervasive alteration is a common feature of metamict minerals. Previous studies of metamict niobium-tantalum-titanium oxides and electron microprobe analyses of altered areas in metamict yttrialite document the leaching of uranium, thorium, and rare earth elements. These data suggest that glasses may not provide a stable medium for radioactive waste disposal. PMID- 17739841 TI - Trypanosomatid flagellate in the Phloem of diseased coconut palms. AB - Ultrastructural observations of the phloem of coconut palms affected by "hartrot" disease in Suriname have revealed the presence of the plant-infecting flagellate Phytomonas in mature sieve tubes. The occurrence of these flagellates during the earliest symptoms of the disease and the correlated increase and spread of the flagellates in the phloem as the disease progresses suggest that the organisms may be pathogenic to the palms. PMID- 17739842 TI - Courtship differences in male ring doves: avoidance of cuckoldry? AB - Male ring doves exhibit less courtship and more aggressive behavior toward females that have recently associated with other males than to females that have been isolated. The difference in response may be related to the differing probability of cuckoldry. PMID- 17739843 TI - PRODUCTS and MATERIALS. PMID- 17739844 TI - THE SOUTH'S POSITION IN THE MINERAL INDUSTRY. PMID- 17739845 TI - THE AGE OF THE EARTH FROM SEDIMENTATION. PMID- 17739846 TI - THE AGE OF THE GALAXY FROM THE DISINTEGRATION OF GALACTIC STAR CLUSTERS AND BINARY STARS. PMID- 17739847 TI - THE AGE OF THE EARTH FROM THE CHANGES IN ITS TEMPERATURE AND ELASTIC PROPERTIES. PMID- 17739848 TI - THE AGE OF THE EARTH FROM RADIOACTIVE DISINTEGRATION AND RELATED PROBLEMS. PMID- 17739850 TI - THE AGE OF THE UNIVERSE FROM THE RED SHIFT IN THE SPECTRA OF EXTRAGALACTIC OBJECTS. PMID- 17739849 TI - ATTEMPTS TO RECONCILE THE LONG AND THE SHORT-TIME SCALES IN COSMOGONY. PMID- 17739851 TI - KILLARNEAN AND EARLIER GRANITE. PMID- 17739852 TI - HUMAN REMAINS IN GRAVEL NEAR WEST UNION, MINN. PMID- 17739854 TI - THE NEW ACTIVE PRINCIPLE OF ERGOT. PMID- 17739853 TI - THE MELODIES OF VERSE. PMID- 17739855 TI - EFFECT OF CORTIN ON INTRA-OCULAR TENSION IN GLAUCOMA. PMID- 17739857 TI - CHANGES IN THE POSITION OF CHICK EMBRYOS AFTER THE EIGHTEENTH DAY OF INCUBATION. PMID- 17739856 TI - CONCANAVALIN A AND HEMAGGLUTINATION. PMID- 17739858 TI - MATERNAL BEHAVIOR IN MALE RATS. PMID- 17739859 TI - STROBOSCOPIC OBSERVATION OF CILIARY MOVEMENT IN THE PROTOZOA. PMID- 17739860 TI - EGG QUANTITY AND THE RESPIRATORY RATES OF SEVERAL MARINE EGGS. PMID- 17739861 TI - DARKFIELD MICROMANIPULATION WITH AN ULTROPAQUE ILLUMINATOR. PMID- 17739862 TI - SCIENCE NEWS. PMID- 17739863 TI - BOTANY AND HUMAN AFFAIRS. PMID- 17739864 TI - THE ABSORPTION OF SOUND IN GASES. PMID- 17739866 TI - JUVENILE CHARACTERS OF ROYAL PALMS. PMID- 17739865 TI - SYNCHRONOUS FIREFLY FLASHING. PMID- 17739868 TI - SCIENTIFIC MEN AND THE NEWSPAPERS. PMID- 17739867 TI - BIOLOGICAL ABSTRACTS. PMID- 17739869 TI - APPROPRIATIONS FOR GRANTS-IN-AID BY THE NATIONAL RESEARCH COUNCIL. PMID- 17739870 TI - THE OHIO ACADEMY OF SCIENCE. PMID- 17739871 TI - AN ILLUMINATOR FOR THE BINOCULAR DISSECTING MICROSCOPE. PMID- 17739872 TI - THE IOWA ACADEMY OF SCIENCE. PMID- 17739873 TI - NEW TOWER FILLING MATERIAL. PMID- 17739875 TI - POTENTIAL RHYTHMS OF THE CEREBRAL CORTEX DURING SLEEP. PMID- 17739874 TI - A MODIFIED BULB PIPETTE. PMID- 17739876 TI - THE CENTRIOLE AND ITS ROLE IN MITOSIS AS SEEN IN LIVING CELLS. PMID- 17739878 TI - THE SMEETH SEPARATING APPARATUS. PMID- 17739877 TI - WEISMANN ON GERMINAL SELECTION. PMID- 17739880 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17739879 TI - CURRENT NOTES ON PHYSIOGRAPHY. PMID- 17739881 TI - THE COLORS NAMED IN LITERATURE. PMID- 17739882 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17739883 TI - PROF. BIGELOW'S SOLAR-MAGNETIC WORK. PMID- 17739884 TI - LIFE HABITS OF PHRYNOSOMA. PMID- 17739885 TI - VARIATIONS OF GLACIERS. PMID- 17739886 TI - BOWS AND ARROWS OF CENTRAL BRAZIL. PMID- 17739888 TI - Demographic data on the elderly. PMID- 17739887 TI - Freedom of Information and NSF. PMID- 17739889 TI - Scientists' Meetings: Collegial versus Positional. PMID- 17739891 TI - Background for the spheroidal nuclear model proposal. PMID- 17739892 TI - Federal vaccine agency: critic fired after bitter conflict. PMID- 17739890 TI - Precambrian geologic history. PMID- 17739894 TI - Nuclear exports and proliferation: the French think they have a case. PMID- 17739893 TI - Venoms: Extracting Healing from the Serpent's Tooth. PMID- 17739895 TI - Jumping genes: a common occurrence in cells. PMID- 17739897 TI - Crustaceans. PMID- 17739896 TI - Early civilization in china. PMID- 17739898 TI - Cancer epidemiology. PMID- 17739899 TI - Lattice vibrations. PMID- 17739900 TI - Alternative transformation behavior in sulfides: direct observations by transmission electron microscopy. AB - Structural phase transformations in Ni(7)S(6) and Cu(7)S(4) have been observed dynamically by in situ experiments in a transmission electron microscope. In this way it is possible to demonstrate the possibility of two fundamentally different types of behavior: (i) the ideal transformation from the stable high-temperature form to the stable low-temperature form and vice versa and (ii) alternative metastable processes which operate when the formation of the low-temperature state is impeded. PMID- 17739901 TI - Trajectory of the mt. St. Augustine 1976 eruption ash cloud. AB - The ash clouds from the 23 January 1976 eruption of Mt. St. Augustine in Alaska drifted over Arizona on 25 January at an altitude of 6 kilometers as deduced from air trajectories and the observation of an unusual cloud. PMID- 17739902 TI - This Week in SCIENCE. PMID- 17739904 TI - Response. PMID- 17739903 TI - Achievable New Year's Resolutions. PMID- 17739905 TI - Sciencescope. PMID- 17739906 TI - Conservation biology in the fast lane. PMID- 17739907 TI - Plant biotechnology explored in indianapolis. PMID- 17739908 TI - Microbes from 20,000 feet under the sea. PMID- 17739909 TI - Superbugs in waiting: some cautionary tales. PMID- 17739910 TI - A fall harvest of Earth science in san francisco: are earthquakes a ticking clock for los angeles? PMID- 17739911 TI - A Fall Harvest of Earth Science in San Francisco: Loma Prieta's Long Reach Was a Matter of Mirrors. PMID- 17739912 TI - A fall harvest of Earth science in san francisco: a conundrum at steens mountain. PMID- 17739913 TI - Fermi surfaces, fermi liquids, and high-temperature superconductors. AB - Recent experimental results are beginning to limit seriously the theories that can be considered to explain high-temperature superconductivity. The unmistakable observations of a Fermi surface, by several groups and methods, make it the focus of realistic theories of the metallic phases. Data from angle-resolved photoemission, positron annihilaton, and de Haas-van Alphen experiments are in agreement with band theory predictions, implying that the metallic phases cannot be pictured as doped insulators. The character of the low energy excitations ("quasiparticles"), which interact strongly with atomic motions, with magnetic fluctuations, and possibly with charge fluctuations, must be sorted out before the superconducting pairing mechanism can be given a microscopic basis. PMID- 17739914 TI - Orientational ordering of polymers by atomic force microscope tip-surface interaction. AB - Results of studies on the interaction between the tip of an atomic force microscope and polystyrene molecules in a film spread on a surface are reported. The tip produces a persistent deformation on the film; some of the polymer molecules are eventually pulled up by the tip. Nanometer-size structures are induced, resulting in a pattern that is periodic and is oriented perpendicular to the scan direction. PMID- 17739915 TI - Luminescent colloidal silicon suspensions from porous silicon. AB - A procedure for generating colloidal suspensions of Si that exhibit luminescence, attributed to quantum confinement effects, is described. Samples of n- or p-type Si that have been electrochemically etched to form porous Si can be ultrasonically dispersed into methylene chloride, acetonitrile, methanol, toluene, or water solvents, forming a suspension of fine Si particles that luminesce. Transmission electron microscopy analyses show that the Si particles have irregular shapes, with diameters ranging from many micrometers to nanometers. Luminescent, composite polystyrene/Si films can be made by the addition of polystyrene to a toluene suspension of the Si nanoparticles and casting of the resulting solution onto a glass slide. PMID- 17739916 TI - Strontium isotopic composition of estuarine sediments as paleosalinity paleoclimate indicator. AB - The strontium isotopic composition of biogenic precipitates that occur in estuarine sediments can be used as proxy indicator of paleosalinity and for assessing precipitation and river discharge rates over thousands of years. In the San Francisco Bay estuary, river water with low (87)Sr/(86)Sr ratio (average, 0.7065) and low Sr concentration (0.13 parts per million) mixes with seawater with a higher (87)Sr/(86)Sr ratio (0.7092) and Sr concentration (7.9 parts per million). The predicted mixing relation between salinity and Sr isotopic composition is confirmed by measurements of modern estuarine surface waters. A paleosalinity record obtained from foraminifera for the ancestral San Francisco Bay during oxygen isotope substage 5e of the last interglacial reflects a global rise and fall of sea level, and short time-scale variations related to fluctuations in discharge rates of the Sacramento and San Joaquin rivers. PMID- 17739917 TI - Production of isotopic variability in continental basalts by cryptic crustal contamination. AB - Regional variations in the Nd, Sr, and Pb isotopic compositions of Neogene basalts from the western United States are commonly interpreted to originate in the subcontinental mantle. In southern California, isotopic variability is restricted to lavas that lack mantle-derived xenoliths; xenolith-bearing basalts have uniform isotopic compositions similar to those of ocean-island basalts (OIBs). Combined with available geochemical data, these observations suggest that isotopic variability at these volcanoes results from subtle crustal contamination, locally by mafic crust, of primitive OIB-like magma. Recognition of such cryptic contamination may help to reconcile local discrepancies between tectonic and isotopic views of the subcontinental mantle. PMID- 17739918 TI - Response. PMID- 17739920 TI - Prices of books. PMID- 17739919 TI - Enumerating buckminsterfullerane isomers. PMID- 17739921 TI - Transformations in social research. PMID- 17739923 TI - Genetic structures. PMID- 17739922 TI - Physical topics. PMID- 17739924 TI - Products & materials. PMID- 17739925 TI - SCIENCE NEWS. PMID- 17739926 TI - PROBLEMS OF THE GLACIALIST. PMID- 17739927 TI - A NEW SCIENCE. PMID- 17739928 TI - THE MICROMETRIC MUDDLE. PMID- 17739929 TI - THE EFFECTIVENESS OF A PLANT QUARANTINE. PMID- 17739930 TI - AN UNBOUND TEXT AND NOTE BOOK. PMID- 17739931 TI - THE DISTRIBUTION OF PAUROPUS. PMID- 17739932 TI - PEDOLOGY OR CHTHONOLOGY? PMID- 17739933 TI - THE AMOUNT OF OSMIC ACID IN FIXING SOLUTIONS NECESSARY TO BLACKEN FAT. PMID- 17739934 TI - A SIMPLE METHOD FOR EXPERIMENTAL PARTHENOGENESIS. PMID- 17739935 TI - THE EFFECT OF ULTRA-VIOLET IN PRODUCING FUSION OF EGGS OF CHAETOPTERUS. PMID- 17739936 TI - VARIATION IN THE PERCENTAGE OF PROTEIN IN THE GRAIN OF A SINGLE WHEAT PLANT. PMID- 17739937 TI - GLUTATHIONE IN PLANT TISSUES. PMID- 17739938 TI - ON THE RECOVERY FOLLOWING LESIONS IN THE CEREBRAL CORTEX. PMID- 17739940 TI - Instrumentation. PMID- 17739939 TI - This Week in SCIENCE. PMID- 17739941 TI - Sciencescope. PMID- 17739943 TI - GOES-NEXT to Wait Out Next Round. PMID- 17739942 TI - A bite out of the market. PMID- 17739945 TI - Whistleblowing for fun and profit. PMID- 17739944 TI - The hunt for drugs from nature. PMID- 17739947 TI - No quick fixes for learning. PMID- 17739946 TI - Water Couldn't Dash This BBQ. PMID- 17739948 TI - U.s. Still balks at greenhouse talks. PMID- 17739949 TI - Doing chemistry in the round. PMID- 17739950 TI - A long look in the extreme ultraviolet. PMID- 17739951 TI - Gamma-ray observatory: bursting with new results. PMID- 17739953 TI - Some Would KO KAON. PMID- 17739952 TI - A frist investment in a kaon factory. PMID- 17739954 TI - Chemical imaging of surfaces with the scanning electrochemical microscope. AB - Scanning electrochemical microscopy is a scanning probe technique that is based on faradaic current changes as a small electrode is moved across the surface of a sample. The images obtained depend on the sample topography and surface reactivity. The response of the scanning electrochemical microscope is sensitive to the presence of conducting and electroactive species, which makes it useful for imaging heterogeneous surfaces. The principles and instrumentation used to obtain images and surface reaction-kinetic information are discussed, and examples of applications to the study of electrodes, minerals, and biological samples are given. PMID- 17739956 TI - Periodic hot-spot distribution on io. AB - The Jovian satellite Io has active volcanic hot spots. The point-to-point correlation of the hot-spot distribution indicates that the hot spots preferentially make chains. The arrangement of the chains is periodic with a typical spacing of 120 kilometers. The chains exhibit concordant trends with stresses imposed by the tidal deflection of the lithosphere, suggesting that the hot spots are formed along fissures in the lithosphere. The typical spacing may be controlled by lithosphere thickness. PMID- 17739955 TI - Chemical microsensors. AB - Rmecent developments in the field of chemical microsensors are leading to new applications for which these devices have the potential to supplement or replace traditional analytical chemical instrumentation. The fundamentals of current microelectronic, acoustic wave, optical fiber, and electrochemical microsensors are presented, and a few recent, exciting results in these areas are described. Although future opportunities in the microsensor field are numerous, many significant problems, the majority of them related to the materials utilized for the chemically sensitive layers that are the "front end" of these devices, remain to be explored and solved. PMID- 17739957 TI - Early cretaceous uplift in the ellsworth mountains of west antarctica. AB - Apatite fission-track analysis of samples covering a 4.2-kilometer vertical section from the western flank of Vinson Massif, Antarctica's highest mountain, indicates that the Ellsworth Mountains were uplifted by 4 kilometers or more during the Early Cretaceous following the initial separation of East and West Gondwana and accompanying the opening of the Weddell Sea. Relief of at least 1.8 kilometers has persisted in the Ellsworth Mountains since the Early Cretaceous, and a maximum of 3 kilometers of uplift has occurred since that time. PMID- 17739958 TI - The AAAS Annual Meeting. PMID- 17739959 TI - Delayed cures. PMID- 17739960 TI - Thinking about food. PMID- 17739961 TI - Evolutionary disentanglement. PMID- 17739963 TI - Chemical abstracts after 75 years. PMID- 17739962 TI - Products & materials. PMID- 17739964 TI - Spectroscopy in a new light. PMID- 17739965 TI - New directors at two institutes. PMID- 17739966 TI - DOD Official Criticizes Export Control Policies. PMID- 17739967 TI - Acoustic tomography of the ocean. PMID- 17739969 TI - LEP Revolution Under Way at CERN. PMID- 17739968 TI - Mathematician solves simplex problem. PMID- 17739970 TI - SWARM Holds Annual Meeting in El Paso. PMID- 17739972 TI - "Report on science' reaches millions with daily radio broadcdsts. PMID- 17739971 TI - "Science: Woman's Work". PMID- 17739973 TI - Major scientfic meetings. PMID- 17739974 TI - 1981 aaas summary financial statements. PMID- 17739975 TI - Water stress in plants. PMID- 17739977 TI - A prominent enzyme. PMID- 17739976 TI - Technological change. PMID- 17739978 TI - Marine ecology for students. PMID- 17739979 TI - Brain development. PMID- 17739980 TI - Primary sulfates in atmospheric sulfates: estimation by oxygen isotope ratio measurements. AB - The relative amounts of primary and secondary sulfates in atmospheric aerosols and precipitation can be estimated from measurements of the stable oxygen isotope ratios. The oxygen-18 content of sulfates formed in power plant stack gases before emission into the atmosphere is significantly higher than that of sulfates formed from sulfur dioxide after emission. Results show that 20 to 30 percent of the sulfates in rain and snow at Argonne, Illinois, are of primary origin. PMID- 17739981 TI - Juvenile-adult habitat shift in permian fossil reptiles and amphibians. AB - Among extant large reptiles, juveniles often occupy different habitats from those of adults or subadults and thus avoid competition with and predation from the older animals; small juveniles often choose cryptic habitats because they are vulnerable to a wide variety of predators. Evidence from fossil humeri and femora of Early Permian reptiles collected from sediments of several distinct habitats indicate that similar shifts in habitat occurred. Juvenile Dimetrodon seem to have favored cryptic habitats around swamp and swampy lake margins; adults favored open habitats on the floodplains. Similar patterns of habitat shift seem to be present in the reptile Ophiacodon and the amphibian Eryops and may have been common in fossil tetrapods of the Permian-Triassic. PMID- 17739982 TI - Carbon functionalities in amber. AB - High-resolution nuclear magnetic resonance spectra of the carbon nuclei in powdered amber, obtained by using the techniques of magic angle spinning and cross polarization, provide detailed information about the types of carbon functionalities. The entire spectrum of Baltic amber (succinite) is identical for several samples. Baltic amber shows minor differences from Sicilian amber and drastic differences from Burmese, Romanian, and Bohemian ambers. PMID- 17739983 TI - Spiroplasmas: diversity of arthropod reservoirs and host-parasite relationships. AB - Spiroplasmas were found in 11 new insect hosts representing four orders: Hymenoptera, Hemiptera, Diptera, and Coleoptera. Three of the new spiroplasmas were serologically distinct from all existing groups or subgroups. A spiroplasma that infects digestive tracts of Colorado potato beetles may be transmitted to uninfected insects that feed on contaminated plants. This simple type of spiroplasma-insect relationship may explain a growing list of isolations of spiroplasmas and other wall-less prokaryotes from plant surfaces. PMID- 17739984 TI - Polar lipids of archaebacteria in sediments and petroleums. AB - Glycerol tetraethers with head-to-head isoprenoid 40-carbon chains that are typical of archaebacteria, in particular of methanogens, were identified in the polar lipids of sediments and petroleums. These structures are at least partially preserved in the subsurface beyond the stage of petroleum formation. Their identification provides further evidence that a significant part of geological organic matter derives from the lipids of membranes of microorganisms. PMID- 17739985 TI - Electroncephalogram tests for brain dysfunation: a question of validity. PMID- 17739986 TI - COMMENT AND CRITICISM. PMID- 17739987 TI - HEALTH OF NEW YORK DURING MARCH. PMID- 17739988 TI - GOVERNMENT SURVEYS. PMID- 17739990 TI - GEOGRAPHICAL NOTES. PMID- 17739989 TI - POPULAR ASTRONOMY. PMID- 17739991 TI - ASTRONOMICAL NOTES. PMID- 17739992 TI - New York agricultural experiment-station. PMID- 17739993 TI - Eskimo building-snow. PMID- 17739994 TI - Settlement of labor differences. PMID- 17739995 TI - World time. PMID- 17739996 TI - Quaternary volcanic deposits in Nebraska. PMID- 17739997 TI - The American ornithologists' union code and check-list of North American birds. PMID- 17739998 TI - Certain questions relating to national endowment of research in this country, and their importance. PMID- 17739999 TI - Food and nutrition. PMID- 17740000 TI - The great food fumble. PMID- 17740001 TI - World food: a perspective. PMID- 17740002 TI - Institutional obstacles to expansion of world food production. AB - It was argued that over the near-to-medium term-roughly to the mid-1980's-there is enough potential for growth in existing Green Revolution technology and in technical capacity of farmers that institutions affecting these two sources of increased food production probably will not be seriously constraining. The principal bottlenecks likely will be found among those institutions affecting farmers' incentives to innovate. There is impressive evidence that when other conditions for innovation are favorable the supply of marketing services, for both inputs and outputs, is quite elastic. This seems to include the supply of funds from rural saving and informal credit sources, although the evidence is less clear in this respect. The situation concerning price relations and availability of inputs appears mixed. If national income growth targets are achieved, then the growth in total demand for food in the LDC's should be fast enough to support incentive prices for farmers. This advantage could be lost, however, if governments adopt policies to suppress food prices to keep down the cost of living. The price of fertilizers is expected to fall from the high levels of 1974, the amount of the fall depending in good measure on the success of the LDC's in increasing fertilizer production. Historically, their efforts to expand capacity have been relatively inefficient. Moreover, many countries still lack adequate capacity to produce the HYV's and pesticides. Even with good progress in expanding domestic production of inputs, imports will continue to be an important source of supply. Maintenance of present high prices of petroleum products could be a major obstacle to financing these imports on the necessary scale because of the drain it would place on available foreign exchange. I conclude, on balance, that prices and availability of fertilizers, pesticides, and seeds could have important negative effects on farmers' incentives to adopt Green Revolution technology. Rigidities in water management institutions may be even more limiting, for reasons noted in the previous section. The role of existing land tenure institutions is not clear. The tentative conclusion, however, is that over the near-to-medium term the maintenance will not be a major obstacle to further spread of the Green Revolution. Over the longer term, it could become more seriously limiting. The reason is that continued expansion of food production will eventually require the invention and adoption of new technologies and a higher level of technical and managerial skill than most farmers in the LDC's now possess. To do this will require substantial investments in domestic research and extension institutions and in rural education. In countries where a small class of large landowners wield substantial political power, these investments may not occur on the necessary scale because the large farmers have their own means of acquiring the technology and little perceived interest in supporting the upgrading of the skills of small farmers. This review of institutional obstacles to expansion of food production in the LDC's must end on a tentative note. The review does suggest some observations about the process of institutional change, however. There is impressive evidence of strong latent potential in the private sector of the LDC's for mobilizing the resources and effort needed for agricultural progress when the private economic rewards for doing so are high. Under these circumstances, needed changes in the institutions required to mobilize the resources and direct the effort seem relatively easy to achieve. Institutional resistance is stronger in situations where influential interests perceive change as a threat or where there is no direct personal economic reward to change, as in the typical public institution. The latter point is particularly important because the performance of public institutions is critical. Development of new technology, the fundamental condition for continued longterm growth, is basically a public responsibility because the gains from adoption usually cannot be sufficiently captured by private institutions to justify their assuming the cost. Although private firms often have incentives to impart technical knowledge to farmers as a way of widening the market for their products, the broadening and strengthening of the institutional structures concerned with both the general and technical education of farmers is a public responsibility. This is true also of the development of large irrigation systems, both because of the scale of the needed investments and the potential for social conflict in water management. The lack of a well-defined mechanism that would link responses of public institutions to the large social payoffs to increased public investment in irrigation, new technology, and technical abilities of farmers may prove in the long run to be the most important single obstacle to adequate growth of food production in the LDC's. PMID- 17740003 TI - Difficult issues underlying food problems. PMID- 17740004 TI - U.s. Agribusiness and agricultural trends. PMID- 17740005 TI - Weather variability, climatic change, and grain production. AB - A cooling trend in the world's climate would have serious effects in the monsoon belts depending on whether or not the recent changes in snow and ice cover in the polar regions were responsible for the droughts in Africa and the failure of the monsoons over South Asia. The cooling and shrinking of the atmosphere at the higher latitudes is believed to have brought the subtropical anticyclones nearer to the tropical rainbelt and have caused a shifting of the monsoon belt. The regions that would be most severely affected by a continuation of the cooling trend to the year 2000 would be the higher latitudes (above 50 degrees) where spring wheat is grown and the warm band below 30 degrees latitude where rice is the principal grain crop. Weather variability is a much more important consideration in grain production than a cooling trend. Our highest yields are made when weather is near normal or slightly cooler than normal. It is when weather variables deviate greatly from normal that yields are lowest. Even if the weather does trend toward the coolness of a century ago yields will not be reduced significantly unless the weather becomes more varible. PMID- 17740007 TI - Agriculture in china. PMID- 17740006 TI - India: a perspective on the food situation. AB - Four major points emerge from this brief survey of the evidence: 1) The food crisis in 1974 seems to have been largely a result of distributional factors. The per capita availability of food grains from all sources, including imports, although below 1971 and 1972 levels, was probably above the average for 1963 to 1973. Comparison of available food supplies with estimated caloric and protein requirements of the population indicates that, on average, enough food was available to meet minimal requirements, with a small margin to spare. Supplies obtained through the government procurement and distribution program were especially short since the program depends primarily on the winter harvest, which failed badly in 1974. Thus, urban areas and some pockets of rural areas were badly hit. The poorest third of the population, who receive 20 to 30 percent less food than the national average even in normal times, were severely affected by higher prices, and there is little doubt that a sizable fraction of the population received inadequate diets. 2) The food supply for 1975 depends heavily on the winter harvest. If this is good, as it promises to be, widespread starvation, but not hunger, should be averted. Since the main shortfall was in the summer crop, the nature of the distribution problem will be different and shortages may be spread more evenly over the population. Nevertheless, the situation seems to forebode considerable hardship for the poorer segments of the population. 3) Food requirements will continue to grow over the foreseeable future as a result of rising population and incomes. India's agricultural resources are still relatively poorly exploited. In the short run, output can probably be increased substantially by increased fertilizer use on traditional as well as new varieties. In the longer run, increased production can be obtained from more intensive cropping, expansion of surface and groundwater irrigation, improved water management, and improved cultural practices brought about by more active agricultural research and appropriate land and pricing policies. These measures will need buttressing by an expanded food storage program if extreme hardships due to periodic drought are to be avoided. 4) India's farmers have shown considerable willingness to innovate under favorable conditions. The rate of adoption of HYV's in the first few years after their introduction was impressive. The same was true for tubewells and fertilizers. Nevertheless, many of the easy gains may already have been made. Fragmentary information on the quality of irrigation indicates that the acreage sown to wheat and rice HYV's may be approaching an upper limit in many areas because of the requirements of these varieties for a high degree of water control. Further gains will require more aggressive and coordinated policies for agricultural development. A major change in development strategy may be required if scarcities and hardships such as those currently being experienced are to be avoided in the future, and some hard political decisions on land reform and consolidation may have to be made. It is to be hoped that bold and imaginative agricultural policies will be followed, and that they will be accompanied by greater efforts to reduce population growth to manageable levels. PMID- 17740008 TI - Human milk, nutrition, and the world resource crisis. PMID- 17740009 TI - Beyond economics and nutrition: the complex basis of food policy. PMID- 17740010 TI - Management of famine relief. AB - We have, over the course of time, made discoveries in compassion as well as discoveries in technology. Many problems that had been judged insoluble in the past are no longer tolerable. For many centuries, starvation was inevitable, largely because means of information and means of transportation were not at hand; the fact that there usually was more food available somewhere else on the same or another continent was irrelevant. There was no way of hearing of the famine, bringing the food where it was needed, or distributing it. We now have the knowledge to install early warning systems based on economic and on medical surveillance (8). Such data as weather reports, crop forecasts, food reserves and retail prices, height-to-weight ratios, skin fold thicknesses, and height-to-arm circumference ratios in children can warn us in advance of impending famine. We also now have the means to transport the food to the area of threatening or actual mass starvation. Therefore, we have obligations that did not exist in past generations. We are now also in a much smaller world from which some of our contemporaries have stepped out to look at the spaceship on which we are all traveling. The worldwide civil rights revolution of the 1960's has brought about greater realization that all human beings are born equal and must be preserved and helped. All this means not only that we must organize to prevent famines on a worldwide basis, but also that we must use the most modern technology to do so. The fact that famine often occurs in remote areas is no reason why we cannot use computers and other modern technology. The very need for programming computers, with the planned coding and feeding of data that it entails, not only forces preparedness but also obliges planners to examine responses to various contingencies. National and international training courses for policy-makers and managers of famine relief should follow. Even if mankind brings its resources and its population into balance, a sound organization of famine relief preparation will still be needed to cope with local contingencies. Rapid agricultural advancement, development of innovative food sources, and, above all, control of population growth are necessary if famine is not to stalk all of mankind in the future. PMID- 17740011 TI - Food production: technology and the resource base. AB - Despite a growing population and increasing demands of that population for improved diets, it appears that the world is not close to universal famine (3, 53). There is enough food now produced to feed the world's hungry (54). That people are malnourished or starving is a question of distribution, delivery, and economics, not agricultural limits. The problem is putting the food where the people are and providing an income so that they can buy it. As to the future, there are clouds on the far horizon. Only increased scientific and technological innovation, coupled with a change in human behavior and in national policy with regard to increased investments in agricultural research, can avert a growing food and population crisis. Only scientists develop new technology. Only farmers produce food. Motivation and incentives are important both for scientific discovery and food production. Agricultural research is also a process. There is no finite beginning or end. It is a continuing search to unravel mysteries. We must force the pace of agricultural development, but technology must be tailored to local conditions. Thiscan be done by scientists who also know how to farm. Individual dedication and sustained government commitments are important. Rapidity of information transfer and of acceptance of technology is also crucial (55). There is a wide gap between progress in research and the point of application for human benefit (Table 5). What accounts for the vast time differences in rapidity of technology acceptance? The current avalanche of new knowledge coupled with problems of food, feed, and fiber supplies, and issues of availability, preservation, protection, renewability, and costs of resources should bring to the front the urgency of rapid information transfer and reassessment of information systems for agricultural and other renewable resources. PMID- 17740012 TI - International agricultural research. PMID- 17740013 TI - Food science in developing countries. AB - It is particularly important for us not to lose sight of the fact that people have been around for a long time and that they achieved remarkable technical skills long before Western science was developed. An anonymous writer from the Food and Agriculture Organization has observed: "It is a commonplace that the fundamental discoveries which made civilization possible-fire- making, tool making, agriculture, building, calculating, writing, money-were all apparently made outside the area which has given us the marvels of modern science" (19). The writer might well have added that it is also commonly overlooked that food technology was not suddenly developed in the 20th century but has been very much a part of the lives of people everywhere ever since they began doing more to their food than gathering it and eating it raw. Lamb's "Essay on Roast Pig" may not be an accurate account of the first conjunction of fire and food, but cooking is a rather ancient practice. Fermentation is another complicated processing technology which is a traditional part of most cultures, particularly those in warm climates-beer, yogurt, cheese, the fish pastes and sauces of Asia, the palm wine of Africa, and soy sauce, are butsome examples. Native Americans, besides accomplishing marvels in plant genetics and crop development, also developed water extraction methods for treating acorns to render the flour palatable and edible, and the alkali method of processing maize. Furthermore, they developed a cure for scurvy-by making a water extraction of pine needles which are rich in ascorbic acid-long before it was first reported by Jacques Cartier in the 16th century. Similarly, calcium-deficient diets of pregnant and nursing women were traditionally successfully supplemented by calcium-rich powdered deer antlers in northern China. Among the Chinese and Greeks, goiter was cured by eating certain kinds of seaweed centuries before the disease was traced to a lack of iodine, and Kenyans learned to suck salt-rich earth to avoid salt depletion symptoms after arduous exertion in tropical heat long before "modern science" learned why (20). The enumeration of examples could go on, but this was not meant to be an essay in folklore. The point is that all so-called primitive societies developed technologies, techniques, and a store of practical knowledge of a wide range of sophistication, by what must be admitted to be the scientific method, and neither their accomplishments and skills nor those of societies "en voie de developpement" should be ignored or discounted. We are confident that modern food science and technology has much to contribute to helping the food-deficit nations eat adequately. First, we must find a way of using the best of Western technology without losing sight of the reality of the situation in the third world and without failing to take into account, better than we have done so far, the secondary and tertiary implications of the changes suggested. Second, we must encourage the examination of local problems in terms of the use and improvement of local technologies which are often quite sophisticated and the result of centuries of development. And third, we must inject a greater component of cultural awareness in the education of students to make them more creative in their application of scientific knowledge to local problems and more adaptable to the conditions that exist in developing countries. We should not lose sight of the fact that because of the precarious nature of their food supply, very often developing countries have much more rigid rules governing the production, preparation, and consumption of food than usually is the case in food-surplus societies, and disturbing these rules is a very serious matter. The time is past when "West is best" can be taken for granted; "adapt and adopt" is surely less offensively arrogant and much more to the point. PMID- 17740014 TI - Crop protection to increase food supplies. PMID- 17740015 TI - Soils of the tropics and the world food crisis. AB - The properties and potential of soils of the tropics are poorly understood. The old idea that laterite is formed when tropical soils are cleared is true of only a small proportion of the area. In most features, soils in the tropics are similar or equivalent to soils in the temperate regions. Specifically, soil organic matter contents, commonly believed to be low in the tropics, are essentially similar to those of the temperate regions. While the basic concepts about physical and chemical behavior developed in the nonglaciated temperate regions are directly applicable to the tropics, the development of soil management practices for sustained food production involves different strategies because of environmental and economic constraints. A major distinction is made between the development of high base status and low base status soils. With the former, soil management practices should be aimed at maximizing the potential of high-yielding varieties and improving intercropping systems with relatively intensive fertilizer inputs. With the low base status soils of the vast savanna and jungle areas energyrelated inputs should be optimized by (i) selecting of crop varieties and species more tolerant to nutritional deficiencies or toxicities, (ii) applying fertilizers at lower rates than those recommended by classic marginal analysis, and (iii) increasing the efficiency of applied fertilizers in such soils. PMID- 17740016 TI - Prospects for high-frequency irrigation. PMID- 17740018 TI - Our vanishing genetic resources. PMID- 17740017 TI - The ganges water machine. PMID- 17740019 TI - Plant cell cultures: genetic aspects of crop improvement. PMID- 17740020 TI - Improving the efficiency of photosynthesis. PMID- 17740021 TI - Nitrogen fixation research: a key to world food? PMID- 17740023 TI - Science bibliography of food. PMID- 17740022 TI - Adaptation of photosynthetic processes to stress. AB - I have focused on examples of plant adaptations to environmental conditions that range from adjustments in the allocation of metabolic resources and modification of structural components to entirely separate mechanisms. The result of these modifications is more efficient performance under the stresses typically encountered in the plants' native habitats. Such adaptations, for reasons which are not entirely clear, often lead to poorer performance in other environmental conditions. This situation may be a fundamental basis for the tendency toward specialization among plants native to specific niches or habitats. The evolutionary mechanisms that have resulted in these specializations are very large-scale processes. It seems reasonable to suppose that the plants native to particular habitats are relatively efficient in terms of the limitations imposed by those habitats, and that the adaptive mechanisms these plants possess are, compared to those which have evolved in competing organisms, the most succesful biological means of coping with the environmental stresses encountered. I believe that we can learn from nature and utilize the adaptive mechanisms of these plants in agriculture to replace in part our present reliance on resources and energy to modify the environment for plant growth. By analogy with natural systems, improved resource utilization will require specialization and greater knowledge of the limitations of a particular environment and plant genotype. For example, the cultural conditions, plant architecture, and physiological responses necessary to achieve high water use efficiency from our crop species with C(4) photosynthesis probably differ from those required to achieve maximum total growth. Also, efforts to control water application to eliminate waste carry with them the risk that the crop could be injured by inadequate water. Thus, greater demands would be placed on the crop physiologist, the plant breeder, and the farmer. Planting and appropriate management of adapted crop genotypes could enable cultivation of many areas presently considered unusable because of environmental extremes or shortage of resources, and may lead to more efficient resource utilization on land already under cultivation. The costs or benefits of this cannot yet be estimated. However, I suspect that the greatest potential for application of such techniques will be in the developing rather than the developed regions of the world. The genetic and functional diversity of plants is a tremendous biological resource. The capacity of plants to adjust in the future to changing environmental conditions depends on this diversity and on evolutionary processes of nature. Wild plants may provide a source of genetic material to improve crop plants. Also, as advocated by McKell (22), wild plants can be utilized to a greater extent directly by man. Long-term research efforts and commitment to preserve natural habitats and their populations of wild plants will be required to maintain and more effectively utilize this resource. PMID- 17740024 TI - ENVIRONMENTAL MEDICINE. PMID- 17740026 TI - NAMING POTTERY TYPES, AND RULES OF PRIORITY. PMID- 17740025 TI - DISTRIBUTION AND UTILIZATION OF FLOOD WATERS. PMID- 17740027 TI - THE INHIBITING INFLUENCE OF A VIRUS ON ONE OF ITS MUTANTS. PMID- 17740029 TI - IODINE THERAPY AND GOITRE. PMID- 17740030 TI - APPARENT INTOXICATION IN POULTRY DUE TO NITROGENOUS BASES. PMID- 17740028 TI - THE EFFECT OF ALTERATION ON THE LEAD-URANIUM RATIO AND THE CALCULATED AGE OF WILBERFORCE, ONTARIO, URANINITE. PMID- 17740031 TI - A TUBE FOR CULTURING FUNGI. PMID- 17740032 TI - THE DIPHASIC ASPECT OF THE CURDLING OF MILK BY RENNIN. PMID- 17740033 TI - RAPID WEIGHINGS WITH A TROEMNER SOLUTION BALANCE. PMID- 17740034 TI - THE NATURE AND PURPOSE OF EDUCATION. PMID- 17740035 TI - THE USES FOR MATHEMATICS. PMID- 17740036 TI - THE LATE WILLIAM SAUNDERS, C.M.G., LL.D. PMID- 17740037 TI - THE MUSEUM OF VERTEBRATE ZOOLOGY OF THE UNIVERSITY OF CALIFORNIA. PMID- 17740038 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17740039 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17740041 TI - X-RAY DIFFRACTION PATTERNS. PMID- 17740042 TI - A NEW METHOD OF PREPARING SPIDERS FOR EXHIBITION IN MUSEUM GROUPS. PMID- 17740040 TI - SUNFLOWER PROBLEMS. PMID- 17740043 TI - MILK EPIDEMICS OF SEPTIC SORE THROAT IN THE UNITED STATES AND THEIR RELATION TO STREPTOCOCCI. PMID- 17740044 TI - THE ARTIFICIAL FERTILIZATION OF QUEEN BEES. PMID- 17740045 TI - THE DYCHE MUSEUM AT THE UNIVERSITY OF KANSAS. PMID- 17740046 TI - SOME UNSOLVED PROBLEMS OF THEORETICAL DYNAMICS. PMID- 17740047 TI - ELMER SAMUEL IMES. PMID- 17740048 TI - MAX KRISS 1894-1941. PMID- 17740049 TI - RESEARCH GRANTS OF THE VIRGINIA ACADEMY OF SCIENCE. PMID- 17740050 TI - THE ADVISORY BOARD ON SANITARY AND PUBLIC HEALTH ENGINEERING. PMID- 17740052 TI - THE AMERICAN CHEMICAL SOCIETY. PMID- 17740051 TI - THE MEETING OF MATHEMATICIANS AT LEHIGH UNIVERSITY. PMID- 17740053 TI - THE DALLAS MEETING OF THE AMERICAN ASSOCIATION. PMID- 17740054 TI - MEAN SEA-LEVEL AND SAND MOVEMENTS. PMID- 17740055 TI - ON THE OCCURRENCE OF STEREOISOMERIC CAROTENOIDS IN NATURE. PMID- 17740056 TI - "THE BREATHING MECHANISM OF TURTLES". PMID- 17740057 TI - ZIPF'S "LAW OF URBAN CONCENTRATION". PMID- 17740058 TI - POST-GRADUATE COURSE IN TROPICAL MEDICINE AT TULANE UNIVERSITY, 1941-1942. PMID- 17740059 TI - LETTER FROM DOUGLAS COCKERELL, LETCHWORTH, ENGLAND, OCTOBER 1, TO HIS BROTHER IN COLORADO. PMID- 17740060 TI - THE PROTECTION OF MICE AGAINST INFECTION WITH AIR-BORNE INFLUENZA VIRUS BY MEANS OF PROPYLENE GLYCOL VAPOR. PMID- 17740061 TI - PROPERTIES OF THE ISOLATED MACROMOLECULAR COMPONENT OF NORMAL CHICK EMBRYO TISSUE. PMID- 17740062 TI - A GRINDER FOR HOMOGENIZING BACTERIAL CLUMPS OR INFECTED TISSUES. PMID- 17740063 TI - CRYSTALLINE CATALASE FROM BEEF ERYTHROCYTES. PMID- 17740064 TI - DENATURATION OF EGG ALBUMIN BY PRESSURE. PMID- 17740065 TI - OSWALD HEER. PMID- 17740066 TI - A HEARING OF BIRDS' EARS.--III. PMID- 17740067 TI - WHIRLWINDS, CYCLONES, AND TORNADOES.--I. PMID- 17740068 TI - THE FRENCH ECLIPSE EXPEDITION. PMID- 17740070 TI - FRENCH GEOGRAPHICAL EXPLORATIONS. PMID- 17740069 TI - THE HIMALAYAS. PMID- 17740071 TI - Francis Galton's proposed 'Family registers.'. PMID- 17740072 TI - Marriage laws of the Omahas and cognate tribes. PMID- 17740073 TI - MAUDSLEY'S BODY AND WILL. PMID- 17740074 TI - EARLY TERRESTRIAL CONDITIONS THAT MAY HAVE FAVORED ORGANIC SYNTHESIS. PMID- 17740076 TI - JAMES FLETCHER. PMID- 17740075 TI - UNIVERSITY REGISTRATION STATISTICS--I. PMID- 17740077 TI - THE SMITHSONIAN INSTITUTION. PMID- 17740078 TI - THE BALTIMORE MEETING. PMID- 17740079 TI - THE RESIGNATION OF PRESIDENT ELIOT. PMID- 17740080 TI - AFTONIAN SANDS AND GRAVEL IN WESTERN IOWA. PMID- 17740081 TI - NOTES ON THE ATROPHY OF THE EYE OF RAJA ERINACEA. PMID- 17740082 TI - THE DETERMINATION OF THE CLAY CONTENT OF SOILS. PMID- 17740084 TI - Medicine for the poor in denver. PMID- 17740083 TI - THE CONVOCATION WEEK MEETINGS OF SCIENTIFIC SOCIETIES. PMID- 17740085 TI - Lake tahoe: measured for pollution. PMID- 17740086 TI - Tenure in 1897. PMID- 17740087 TI - Population stabilization. PMID- 17740088 TI - Support the theoretical thinkers! PMID- 17740089 TI - New quarks for physics. PMID- 17740090 TI - Touche. PMID- 17740091 TI - A tax-saving spin off. PMID- 17740093 TI - The semiconductor revolution in nuclear radiation counting. PMID- 17740092 TI - Coping with the information explosion. PMID- 17740094 TI - Detection and measurement of pesticide residues. PMID- 17740095 TI - Image tubes in astronomy. PMID- 17740096 TI - Restoration of photographs by neutron activation. AB - Badly faded or stained photographs or radiographs, negative or positive, can be restored by use of neutron activation and autoradiography, provided that at least a trace of image silver is present and that the picture is relatively free of halogens and other silver. PMID- 17740097 TI - Detection of relativistic particles. AB - It appears possible to extend the application of most of the existing detection techniques to the identification and separation of charged particles in the relativistic energy region.One can probably extend these applications, in certain limited cases, up to an energy region of several hundred billion electron volts. However, for general applications in the identification of particles in the ultrarelativistic region, the existing detectors are rather limited, and new methods and approaches are desirable. At present, detectors making use of the relativistic rise effect seem to show considerable promise. PMID- 17740098 TI - The Smale Case: NSF and Berkeley Pass Through a Case of Jitters. PMID- 17740100 TI - Grand canyon dams: interior to ask, "are they necessary?". PMID- 17740099 TI - Scientist-astronauts: only the "perspicacious" need apply. PMID- 17740101 TI - John F. Kennedy School: Helping Government's "In-and-Outers". PMID- 17740102 TI - A braille-reading machine. AB - A new system for publishing and presenting Braille text is delineated. The system requires a new device for actual "reading." Experiments to determine reader preference and acceptance of the device are presented, and performance criteria on the device are listed. PMID- 17740103 TI - Turbulent-gas chromatography. AB - Turbulent flow in gas chromatography was achieved and its effect was studied with high-speed, high-pressure equipment. A gas-solid capillary and several packed columns were used. The onset of turbulence was associated with abrupt decrease in peak width in the capillary and gradual leveling off and decrease in the Packed width in the existence of separation under turbulent conditions was shown. The Potential of the method was demonstrated by its short elution times and generation of theoretical Plates. PMID- 17740104 TI - Oxygen consumption of a flying bird. AB - Budgerygahs (Melopsittacus undulatus) flew with a minimum oxygen consumption of 38 milliliters per gramhour at each of three speeds between 19 and 33 kilometers per hour in a recirculating wind tunnel. An oxygen debt accumulated in the first minute of flight and was repaid in the minute following cessation of flight. Frequency of wingbeat was independent of flight speed. The data suggest that flying budgerygahs have a higher cardiac output per kilogram of body weight than mammals and that flight muscle of the budgerygah is among the most metabolically active tissues known. PMID- 17740105 TI - Pholidostrophiid brachiopods: origin of the nacreous luster. AB - The "nacreous" luster characteristic of the pholidostrophiid group of fossil brachiopods results from a shell structure that produces superimposed sets of natural optical-diffraction gratings made of calcite. The wall structure is crossed lamellar, parallel to the shell surfdce; thus flakiness and development of reflecting surfaces are facilitated. PMID- 17740106 TI - THE INTERPRETATION OF NATURE AND THE TEACHING LABORATORY. PMID- 17740107 TI - THE FITNESS OF ORGANISMS FROM AN EMBRYOLOGIST'S VIEWPOINT. PMID- 17740108 TI - THE FINAL EXAMINATION OF SENIORS IN AMERICAN COLLEGES. PMID- 17740110 TI - UNIVEBSITY AND EDUCATIONAL NEWS. PMID- 17740109 TI - WILLIAM MCMURTBIE. PMID- 17740112 TI - A PHLEBOTOMUS THE PRACTICALLY CERTAIN CARRIER OF VERRUGA. PMID- 17740111 TI - THREE ICE STORMS. PMID- 17740113 TI - BRANCH MOVEMENTS INDUCED BY CHANGES OF TEMPERATURE. PMID- 17740114 TI - "YELLOW" AND "AGOUTI" FACTORS IN MICE. PMID- 17740115 TI - ANTIGRAVITATIONAL GRADATION. PMID- 17740116 TI - This week in science. PMID- 17740117 TI - The lost u.s. Excellence in manufacturing. PMID- 17740118 TI - Grand canyon haze. PMID- 17740119 TI - In reply: grand canyon haze. PMID- 17740120 TI - In reply: grand canyon haze. PMID- 17740121 TI - The Florida case: appearances matter. PMID- 17740122 TI - Harvard's Tough New Rules. PMID- 17740123 TI - Should science journals play cop? PMID- 17740124 TI - Freshman Chemistry Was Never Like This: To battle science illiteracy among college students, the New Liberal Arts program tries a fresh approach to teaching science. PMID- 17740125 TI - Teaching science appreciation. PMID- 17740126 TI - The Fringe of the Ocean--Under Siege from Land: The ecology of the ocean margins, crucial to human life, is being disrupted by our activities--and perhaps by global change. PMID- 17740129 TI - Physics award yields high return. PMID- 17740127 TI - Irrationality--skeptics strike back. PMID- 17740128 TI - Cocaine shrinks your brain? PMID- 17740130 TI - A wasp by any other smell . . PMID- 17740131 TI - Sudanese scientists. PMID- 17740132 TI - Correction. PMID- 17740133 TI - Teasing young minds with biology. PMID- 17740134 TI - What the Longest Exposures from the Hubble Space Telescope Will eveal. AB - Detailed simulations are presented of the longest exposures on representative fields that will be obtained with the Hubble Space Telescope, as well as predictions for the numbers and types of objects that will be recorded with exposures of different durations. The Hubble Space Telescope will reveal the shapes, sizes, and content of faint, distant galaxies and could discover a new population of Galactic stars. PMID- 17740135 TI - Efficient multistep photoinitiated electron transfer in a molecular pentad. AB - A synthetic five-part molecular device has been prepared that uses a multistep electron transfer strategy similar to that of photosynthetic organisms to capture light energy and convert it to chemical potential in the form of long-lived charge separation. It consists of two covalently linked porphyrin moieties, one containing a zinc ion (P(Zn)) and the other present as the free base (P). The metailated porphyrin bears a carotenoid polyene (C) and the other a diquinone species (Q(A)-Q(B)). Excitation of the free-base porphyrin in a chloroform solution of the pentad yields an initial charge-separated state, C-P(Zn)-P(.+). Q(A)(-)-Q(B), with a quantum yield of 0.85. Subsequent electron transfer steps lead to a final charge-separated state, C(.+)-P(Zn)-P-Q(A)-Q(B)(.-), which is formed with an overall quantum yield of 0.83 and has a lifetime of 55 microseconds. Irradiation of the free-base form of the pentad, C-P-P-Q(A)-Q(B), gives a similar charge-separated state with a lower quantum yield (0.15 in dichloromethane), although the lifetime is increased to approximately 340 microseconds. The artificial photosynthetic system preserves a significant fraction ( approximately 1.0 electron volt) of the initial excitation energy (1.9 electron volts) in the long-lived, charge-separated state. PMID- 17740136 TI - Holocene mean uplift rates across an active plate-collision boundary in taiwan. AB - Samples of Holocene fossil coral from uplifted reefs of three tectonically distinct, yet geographically proximal regions of Taiwan have been dated by uranium-series and (14)C isotopes. Applying corrections for altitude change caused by sea level fluctuations enables evaluation of long-term average Holocene uplift rates for three areas across an active convergent margin: (i) the Hengchun Peninsula of the Eurasian tectonic plate; (ii) the Eastern Coastal Range of Taiwan, a plate boundary; and (iii) two offshore islands, Lanyu and Lutao, both situated on the leading edge of the adjoining Philippine Plate. The data indicate that while all three areas have experienced uplift through the Holocene, plate collision has caused significantly higher uplift rates in the region directly along the plate boundary. PMID- 17740137 TI - Deforestation history of the eastern rain forests of madagascar from satellite images. AB - Madagascar is biologically one of the richest areas on Earth, and its plants and animals are among the most endangered. Satellite images and vegetation maps based on earlier aerial photographs were used to determine the extent of eastern rain forests in Madagascar and to monitor the rate of deforestation over a 35-year period. In 1985, 3.8 million hectares of rain forest remained, representing only 50 percent of the 7.6 million hectares existing in 1950 and 34 percent of the estimated orignal extent (11.2 million hectares). Between 1950 and 1985, the rate of deforestation averaged 111,000 hectares per year. Deforestation was most rapid in areas with low topographic relief and high population density. If cutting of forests continues at the same pace, only forests on the steepest slopes will survive the next 35 years. PMID- 17740138 TI - Code of ant-plant mutualism broken by parasite. AB - Newly discovered Phyllobaenus beetles are parasites of a mutualism. Piper ant plants in tropical forests provide lipid and protein-rich food cells and shelter for Pheidok bicornis ants while the ants remove small herbivores and vines from the foliage. In contrast to all other ant-plants, Piper ant-plants produce food bodies only when Pheidole bicornis is present in the plant. However, Phyllobaenus beetles can stimulate the plants to produce food bodies as if ants were present. The beetles then inhabit the plant, exploiting nest sites and food produced by the plants for ants. These beetles may also prey on ant brood, depriving the plants of resources and services provided by the ants. PMID- 17740139 TI - The Myth of Heterosexual AIDS. Michael Fumento. Basic Books, New York, 1990. xiv, 404 pp. $22.95. A New Republic Book. PMID- 17740141 TI - GARBAGE-CREMATION. PMID- 17740140 TI - Products & materials. PMID- 17740143 TI - SCIENTIFIC NEWS IN WASHINGTON. PMID- 17740142 TI - THE NEW SPRAGUE ELECTRIC-MOTOR TRUCK. PMID- 17740144 TI - A Queer Game among the Navajo. PMID- 17740145 TI - Human Beasts of Burden. PMID- 17740146 TI - COMMELIN, DESMAURES, AND BAILHACHE STORAGE-BATTERY. PMID- 17740147 TI - THE ACTION OF ELECTRICITY OF THE VESICLES OF CONDENSED STEAM. PMID- 17740148 TI - ELECTRICAL NEWS. PMID- 17740150 TI - ELECTRIC-LIGHTING. PMID- 17740149 TI - AN ELECTRIC SURFACE ROAD IN NEW YORK. PMID- 17740152 TI - THE EICKEMEYER DYNAMO. PMID- 17740151 TI - TRIAL OF AN ELECTRIC LOCOMOTIVE AT BIRMINGHAM. PMID- 17740153 TI - THE EDISON ELECTRIC-LIGHTING SYSTEM IN BERLIN. PMID- 17740154 TI - COMMERCIAL GEOGRAPHY. PMID- 17740155 TI - Pseudo-scientific Humbuggery. PMID- 17740157 TI - Rosenbusch's Petrography. PMID- 17740156 TI - New York Archaeology. PMID- 17740158 TI - Species and Subspecies: A Reply to Mr. Conn. PMID- 17740159 TI - Queries. PMID- 17740160 TI - A Correction. PMID- 17740161 TI - Of Books and Reading. PMID- 17740163 TI - What's RIGHT with Science News Reporting? PMID- 17740162 TI - The Psychosemanticist Will See You Now, Mr. Thurber. PMID- 17740164 TI - The Educated Man in 1984. PMID- 17740165 TI - English Style in Scientific Papers. PMID- 17740166 TI - Suggestions for Contributors to Science. PMID- 17740168 TI - Use and Abuse of English in Science. PMID- 17740167 TI - News of Science. PMID- 17740169 TI - Wisconsin's Science Writing Program. PMID- 17740170 TI - New Look in Soviet Genetics. PMID- 17740172 TI - International Geophysical Year Symbol. PMID- 17740171 TI - Library Searches with Punched-Card Machines. PMID- 17740174 TI - Dangerous Dagger. PMID- 17740173 TI - Subject Indexing in a Restricted Field. PMID- 17740176 TI - Verifying Useless Knowledge. PMID- 17740175 TI - Committee on Mathematical Biology. PMID- 17740177 TI - High-School Students as Laboratory Assistants. PMID- 17740178 TI - Index of Books Reviewed in SCIENCE, 15 April 1955 through 20 April 1956. PMID- 17740180 TI - Forthcoming Events. PMID- 17740182 TI - MEDICINE AND THE UNIVERSITY. PMID- 17740181 TI - LORD KELVIN. PMID- 17740183 TI - TWO NEW METEORITES. PMID- 17740184 TI - SOME LIFE-HISTORY NOTES ON MEGARHINUS SEPTENTRIONALIS2 D. AND K. PMID- 17740185 TI - DR. ARMSBY'S NEW UNIT FOR ENERGY. PMID- 17740186 TI - DISSOROPHUS--A CORRECTION. PMID- 17740188 TI - CURRENT NOTES ON LAND FORMS. PMID- 17740187 TI - THE PENEPLAIN OF NORTH CENTRAL WISCONSIN. PMID- 17740189 TI - THE WORK OF OUR LARGER MUSEUMS AS SHOWN BY THEIR ANNUAL REPORTS. PMID- 17740190 TI - THE GENERAL MEETING OF THE AMERICAN PHILOSOPHICAL SOCIETY. PMID- 17740191 TI - THE PRODUCTION OF MUSICAL NOTES FROM NONMUSICAL SANDS. PMID- 17740193 TI - SEA-SIOKNESS. PMID- 17740192 TI - DIET AND ANIMAL TEMPERATURE. PMID- 17740194 TI - EVOLUTION. PMID- 17740195 TI - RELATIONS OF TEMPERATURE TO VERTEBRAE AMONG FISHES. PMID- 17740196 TI - Number of Words in an Ordinary Vocabulary. PMID- 17740199 TI - DROPSICAL DISEASES OF PLANTS. PMID- 17740197 TI - Fair-Weather Echoes. PMID- 17740198 TI - Climatic Changes in the Southern Hemisphere. PMID- 17740201 TI - INTERPRETATION OF MAYA HIEROGLYPHS BY THEIR PHONETIC ELEMENTS.--I. PMID- 17740200 TI - THE SPEECH OF ANIMALS. PMID- 17740202 TI - DOUBLE SURFACES. PMID- 17740204 TI - ESKIMO TRACES IN NEW YORK. PMID- 17740203 TI - BOTANICAL NOTES FROM WESTERN PENNSYLVANIA. PMID- 17740205 TI - A PECULIAR FLORA IN CHICAGO. PMID- 17740206 TI - FEIGNED DEATH IN SNAKES. PMID- 17740207 TI - TELLURIDE OF GOLD, CRIPPLE CREEK, COLORADO. PMID- 17740208 TI - LATE-BLOOMING TREES. PMID- 17740209 TI - THE HARDNESS OF CARBORUNDUM. PMID- 17740210 TI - DR. TOPINARD AND THE SERPENT MOUND. PMID- 17740211 TI - FEIGNED DEATH IN SNAKES. PMID- 17740212 TI - A MINIATURE WATER LILY. PMID- 17740213 TI - THE VAN'T HOFF CELEBRATION. PMID- 17740215 TI - SOME OF THE PROBLEMS OF LIMNOLOGY. PMID- 17740214 TI - THE MEETING OF NATURALISTS AT CHICAGO. PMID- 17740216 TI - A PRELIMINARY ACCOUNT OF SOME OF THE RESULTS OF THE PLANKTON WORK OF THE ILLINOIS BIOLOGICAL STATION. PMID- 17740217 TI - MALARIA AND TUBERCULOSIS. PMID- 17740218 TI - DO THE REACTIONS OF THE LOWER ANIMALS AGAINST INJURY INDICATE PAIN SENSATIONS? PMID- 17740219 TI - PLANT MATERIAL FOR LABORATORY USE IN THE SCHOOLS. PMID- 17740221 TI - EDUCATION IN THE UNITED STATES. PMID- 17740220 TI - DO FISHES REMEMBER? PMID- 17740222 TI - THE GERMAN CONSULAR SERVICE. PMID- 17740223 TI - EDUCATION ADMINISTRATION IN THE STATE OF NEW YORK. PMID- 17740224 TI - INDIAN UNIVERSITY FOR RESEARCH. PMID- 17740225 TI - Subpoenas: show probable cause. PMID- 17740226 TI - Universities and the technology gap. PMID- 17740227 TI - Optical Astronomy's Two New 150-Inch Telescopes: The National Science Foundation and Ford Foundation are funding large telescopes for basic research. PMID- 17740229 TI - Defense research: senate critics urge redeployment to urban needs. PMID- 17740228 TI - Physics and the Polity: Are physics and society on divergent courses? PMID- 17740231 TI - Social science: british council has key role in research support. PMID- 17740232 TI - Senator Harris: A Man Concerned about Research, Poverty, Indians. PMID- 17740233 TI - Dead sheep show signs of nerve gas. PMID- 17740234 TI - Dating Works of Art through Their Natural Radioactivity: Improvements and Applications. AB - The method for approximately dating white lead, which is based upon the decay of lead-210 present in recently refined lead, has been modified to circumvent potential interferences. The modified method has been applied to additional samples of known age and finds increased utility through special treatment of the obtained data. The method was also successfuilly applied to a number of interesting problems of authentication. PMID- 17740235 TI - Optical pulse of a periodic radio star. AB - The pulsating radio star reported by Hewish et al. (1) has been studied in the blue region of the optical spectrum and found to have a pulse amplitude less than 10 percent of the photon count expected for 18th magnitude. No upper limit to a sinusoidal oscillation less than or equal to a complete modulation can be set. PMID- 17740236 TI - Pulse structure of the pulsating radio source in vulpecula. AB - The pulses from the pulsating radio source at right ascension 19 hours 19 minutes, declination +22 degrees have the following characteristics: (i) they begin with a sharp leading edge; (ii) they terminate after 37 milliseconds; and (iii) they consist of three subpulses, the first of which is both the strongest and the best defined. PMID- 17740237 TI - Oxygenation: a specific soluble cytochrome p-450 coupled enzyme complex. PMID- 17740238 TI - Biochemical Evidence for the Incorporation of Nucleotides during the Rejoining of Bacteriophage DNA Fragments. PMID- 17740240 TI - Electric power from solar radiation. PMID- 17740239 TI - Cause of gastric ulcers. PMID- 17740241 TI - Utilization of accentuated environmental inequalities in research on racial differences. PMID- 17740242 TI - Toroidal magnetic fields for stable plasma confinement. PMID- 17740243 TI - Information Processing in Fish Lateral-line Sense Organs. PMID- 17740244 TI - Patterns of mental ability and socioeconomic status. PMID- 17740245 TI - Proteins in bioelectrogenesis: the control of ion movements in excitable membranes. PMID- 17740247 TI - Action of Sodium Acetylsalicylate upon Body Temperature of the Cat. PMID- 17740246 TI - Behavior of a collisionless plasma confined by a toroidal multipole magnetic field. PMID- 17740248 TI - Metal site of nonheme (iron-sulfur) proteins. PMID- 17740249 TI - Influence of Atmospheric Stability Layers on the Effect of Ground-Based Cloud Seeding: II. Hypotheses in Explanation. PMID- 17740250 TI - Influence of atmospheric stability layers on the effect of ground-based cloud seeding: I. Empirical results. PMID- 17740251 TI - A "try simplest cases" resolution of the energy-momentum tensor controversy for electromagnetic fields in matter. PMID- 17740252 TI - New test of general relativity: preliminary results. PMID- 17740253 TI - Influence of Atmospheric Stability Layers on the Effect of Ground-Based Cloud Seeding: III. Classification of Weather Types. PMID- 17740254 TI - Density distribution in the Earth. PMID- 17740255 TI - Chemical analysis of the lunar surface at the surveyor landing sites. PMID- 17740256 TI - Immunological properties of colicine k. PMID- 17740257 TI - Study of monozygous quadruplet armadillos in relation to Mammalian inheritance. PMID- 17740258 TI - Proposed research to reduce racial aspects of the environment-heredity uncertainty. PMID- 17740259 TI - Analysis of scientific productivity. PMID- 17740260 TI - Tetrodotoxin: a nonlethal paralytic agent for insects. PMID- 17740261 TI - Biological and mechanical role of soil fungi. PMID- 17740262 TI - FUNGOUS DISEASES OF PLANTS. PMID- 17740263 TI - THE TRIPP ANTI-FRICTION ROLLER-BEARING. PMID- 17740264 TI - A NEW RECORDING PRESSURE-GAUGE. PMID- 17740265 TI - NOTES OF TOMATOES. PMID- 17740266 TI - HEREDITY OF ACQUIRED CHARACTERISTICS. PMID- 17740267 TI - SMALL-POX. PMID- 17740268 TI - AFRICAN JUMPERS. PMID- 17740270 TI - THE STOMACH-BRUSH. PMID- 17740269 TI - VACCINATION ON THE LEG. PMID- 17740271 TI - HEALTH MATTERS. PMID- 17740272 TI - AMERICAN SOCIETY OF MECHANICAL ENGINEERS. PMID- 17740273 TI - STANLEY AND EMIN. PMID- 17740275 TI - INDUSTRIAL NOTES. PMID- 17740274 TI - BARNACLES. PMID- 17740276 TI - This week in science. PMID- 17740277 TI - Computers. PMID- 17740278 TI - Filamentary structures. PMID- 17740279 TI - "Money pot" clarified. PMID- 17740281 TI - Erratum. AB - In the Table of Contents of the issue of 14 February (p. 653), the title of the report on page 731 by R. S. Ostrow et al. should have been "Detection of papillomavirus DNA in human semen." PMID- 17740280 TI - U.s. Science and technology. PMID- 17740282 TI - Human rights and credibility. PMID- 17740283 TI - Shuttle Inquiry Focuses on Weather, Rubber Seals, and Unheeded Advice: Thiokol engineers warned against launching because of doubts about the performance of seals between segments of the booster rocket at low temperatures. PMID- 17740284 TI - Education Makes Comeback at NSF: After being abolished when Reagan came to office, the education directorate now has a steady budget and is gaining credibility among its critics and within the foundation. PMID- 17740285 TI - A SWAT Team for Nuclear Accidents: The NRC, under pressure to improve its accident analysis, has installed a new system that demands fast detective work and quick reporting. PMID- 17740286 TI - UN Biotechnology Center Mired in Politics. PMID- 17740287 TI - DOD Proposes Rules for Reviewing Scientific Papers. PMID- 17740288 TI - Voyage to a Blue Planet:: As in its previous encounters with Jupiter and Saturn, Voyager 2 provided an abundance of data at Uranus--and a generous helping of surprise, puzzlement, and wonder. PMID- 17740290 TI - Computer networking for scientists. AB - Scientific research has always relied on communication for gathering and providing access to data; for exchanging information; for holding discussions, meetings, and seminars; for collaborating with widely dispersed researchers; and for disseminating results. The pace and complexity of modern research, especially collaborations of researchers in different institutions, has dramatically increased scientists' communications needs. Scientists now need immediate access to data and information, to colleagues and collaborators, and to advanced computing and information services. Furthermore, to be really useful, communication facilities must be integrated with the scientist's normal day-to day working environment. Scientists depend on computing and communications tools and are handicapped without them. PMID- 17740291 TI - Perspectives on artificial intelligence programming. AB - Programs are judged not only by whether they faithfully carry out the intended processing but also by whether they are understandable and easily changed. Programming systems for artificial intelligence applications use specialized languages, environments, and knowledge-based tools to reduce the complexity of the programming task. Language styles based on procedures, objects, logic, rules, and constraints reflect different models for organizing programs and facilitate program evolution and understandability. To make programming easier, multiple styles can be integrated as sublanguages in a programming environment. Programming environments provide tools that analyze programs and create informative displays of their structure. Programs can be modified by direct interaction with these displays. These tools and languages are helping computer scientists to regain a sense of control over systems that have become increasingly complex. PMID- 17740289 TI - The next generation of personal computers. AB - Surprisingly affordable workstations with powerful graphics and computational capabilities will be on the desks of students and professionals within the next 2 years. Leading computer manufacturers and universities are creating a UNIX-based systems software regime that allows for portable applications software that can run on a wide range of workstations and that exploits emerging technologies. PMID- 17740292 TI - Knowledge-based systems. AB - First developed two decades ago, knowledge-based systems have seen widespread application in recent years. While performance has been a strong focus of attention, building such systems has also expanded our conception of a computer program from a black box providing an answer to something capable of explaining its answers, acquiring new knowledge, and transferring knowledge to students. These abilities derive from distinguishing clearly what the program knows from how that knowledge will be used, making it possible to use the same knowledge in different ways. PMID- 17740293 TI - Small shared-memory multiprocessors. AB - Multiprocessors built from today's microprocessors are economically attractive. Although we can use these multiprocessors for time-sharing applications, it would be preferable to use them as true parallel processors. One key to achieving efficient parallel processing is to match the communications capabilities of the multiprocessor to the communications needs of the problem. The other key is improved parallel programming systems. If these are achieved, then efficient parallel processing can be approached from both ends by providing more communications capability in the hardware and restructuring the problem to reduce the communications requirements. PMID- 17740294 TI - Parallel supercomputing today and the cedar approach. AB - More and more scientists and engineers are becoming interested in using supercomputers. Earlier barriers to using these machines are disappearing as software for their use improves. Meanwhile, new parallel supercomputer architectures are emerging that may provide rapid growth in performance. These systems may use a large number of processors with an intricate memory system that is both parallel and hierarchical; they will require even more advanced software. Compilers that restructure user programs to exploit the machine organization seem to be essential. A wide range of algorithms and applications is being developed in an effort to provide high parallel processing performance in many fields. The Cedar supercomputer, presently operating with eight processors in parallel, uses advanced system and applications software developed at the University of Illinois during the past 12 years. This software should allow the number of processors in Cedar to be doubled annually, providing rapid performance advances in the next decade. PMID- 17740295 TI - Massively Parallel Computers: The Connection Machine and NON-VON. AB - The demand for high-speed computers is increasing, and as the limits on single processor computers are approached, researchers are turning their attention to parallel computers. Parallel computers have more than one processing element; massively parallel computers contain many processing elements. Constructing computers on this scale and learning how to program them effectively will be major challenges in the next decade. Several such computers, for example the Connection Machine and the NON-VON, are under development. PMID- 17740296 TI - Evolution of the ratio of strontium-87 to strontium-86 in seawater from cretaceous to present. AB - A detailed record of the strontium-87 to strontium-86 ratio in seawater during the last 100 million years was determined by measuring this ratio in 137 well preserved and well-dated fossil foraminifera samples. Sample preservation was evaluated from scanning electron microscopy studies, measured strontium-calcium ratios, and pore water strontium isotope ratios. The evolution of the strontium isotopic ratio in seawater offers a means to evaluate long-term changes in the global strontium isotope mass balance. Results show that the marine strontium isotope composition can be used for correlating and dating well-preserved authigenic marine sediments throughout much of the Cenozoic to a precision of +/ 1 million years. The strontium-87 to strontium-86 ratio in seawater increased sharply across the Cretaceous/Tertiary boundary, but this feature is not readily explained as strontium input from a bolide impact on land. PMID- 17740298 TI - A biogeographic event: the great american biotic interchange. PMID- 17740297 TI - AAAS Annual Meeting Philadelphia, 25-30 May 1986. PMID- 17740299 TI - Brain asymmetries: cerebral lateralization in nonhuman species. PMID- 17740300 TI - Atmosphere physics: physical meteorology. PMID- 17740301 TI - Products & materials. PMID- 17740302 TI - SOME GENERAL IMPRESSIONS. PMID- 17740303 TI - THE FIFTH CLEVELAND MEETING OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE AND ASSOCIATED SOCIETIES. PMID- 17740304 TI - THE PRESIDENTIAL ADDRESS. PMID- 17740306 TI - REGISTRATION. PMID- 17740305 TI - GENERAL SESSIONS. PMID- 17740307 TI - NATIONAL GEOGRAPHIC SOCIETY-SMITHSONIAN INSTITUTION LECTURE. PMID- 17740308 TI - ANNUAL ASSOCIATION-PHI BETA KAPPA ADDRESS. PMID- 17740309 TI - ANNUAL ASSOCIATION-SIGMA XI ADDRESS. PMID- 17740310 TI - GENERAL SYMPOSIA. PMID- 17740311 TI - SECTION AND SOCIETY PROGRAMS: SECTION ON MATHEMATICS (A). PMID- 17740312 TI - MINUTES OF THE COUNCIL MEETING. PMID- 17740314 TI - THE ACADEMY CONFERENCE. PMID- 17740315 TI - THE UNITED NATIONS STANDARDS COORDINATING COMMITTEE. PMID- 17740316 TI - MEMORIAL MEETING IN HONOR OF MARIE SKLODOWSKA CURIE. PMID- 17740313 TI - EXPENSES OF THE CLEVELAND MEETING. PMID- 17740317 TI - THE NATIONAL INDUSTRIAL CHEMICAL CONFERENCE AND THE CHEMICAL EXPOSITION. PMID- 17740319 TI - FUNDAMENTAL BIOLOGICAL RESEARCH IN WARTIME. PMID- 17740318 TI - COMMENTS ON COMPARATIVE STUDIES IN HUMAN BIOLOGY. PMID- 17740320 TI - THE CORRECT NAMES OF PARASITES IN HUMAN MALARIA. PMID- 17740321 TI - THE GENERIC NAME OF THE SAND FLY. PMID- 17740322 TI - EXPERIMENTAL AND CLINICAL OBSERVATIONS ON INCREASED MECHANICAL FRAGILITY OF ERYTHROCYTES. PMID- 17740323 TI - PROGRESSIVE ASCENDING PARALYSIS IN DOGS DUE TO DEFICIENCY OF A VITAMIN B COMPLEX FACTOR FOUND IN YEAST. PMID- 17740324 TI - ENHANCED PRODUCTION OF PENICILLIN IN FLUID MEDIUM CONTAINING CELLOPHANE. AB - Enhanced production of penicillin is made possible by addition of Cellophane to fluid media. With Cellophane bags of suitable surface, the growth of the submerged and surface penicillin producing strains of Penicillium notatum is significantly faster and more abundant; penicillin makes its appearance earlier and reaches higher concentration in larger total volumes than in control cultures without Cellophane. Thus the gain with the method described is both in the rate of production as well as in the total yield of penicillin. The enhancement also occurs under conditions unfavorable for development of penicillin, namely, (a) with degenerated cultures of the mold; and (b) when the surface penicillin producing strain is grown in cultures with an unfavorably small [See Equation In PDF file] ratio (0.0315). There is also noted a markedly stabilizing effect of Cellophane upon the H-ion concentration of abundantly growing cultures during active production of penicillin. The stabilization is of significance, since the sharp rise in pH usually occurring in Penicillium cultures tends to destroy rapidly the penicillin. PMID- 17740325 TI - PRELIMINARY NOTE ON THE INACTIVATION OF ANTIBIOTICS. PMID- 17740327 TI - Oil spils. PMID- 17740326 TI - This week in science. PMID- 17740328 TI - Educational reform. PMID- 17740329 TI - Climate and forests. PMID- 17740330 TI - "I am not a neat person". PMID- 17740331 TI - NIH to Use Forensics. PMID- 17740332 TI - A question of intent. PMID- 17740333 TI - Electrochemists Fail to Heat Up Cold Fusion: The meeting was supposed to be a chance to strengthen the case for cold fusion, but it did not work out quite as planned. PMID- 17740334 TI - Researchers irked by changes to testimony. PMID- 17740335 TI - Germany sets up new space agency. PMID- 17740336 TI - Science artifacts on the block. PMID- 17740337 TI - Skeleton Alleged in the Stealth Bomber's Closet: A 40-year-old dispute over the range of "flying wing" aircraft has been resurrected in a critique of the B-2. PMID- 17740338 TI - Observations in particle physics from two neutrinos to the standard model. AB - The two-neutrino experiment established a relationship between particles, muon and muon neutrino, electron and electron neutrino, which evolved into the standard model of particle physics. The theme of this article is a personal one, which reviews a series of experiments at the Columbia Synchrocyclotron, the Brookhaven Cosmotron, the Alternating Gradient Synchrotron, the CERN intersecting storage rings, the Fermilab 400-gigavolt proton synchrotron, and the Cornell electron storage rings, all of which were important in the evolution of the standard model. In some cases the fermion particles were discovered (the second neutrino vmicro, b quark); in other cases fields of research were opened (muon spin resonance, neutral kaons and charge-parity violation, dimuons and the Drell Yan process), which led to further development of the standard model. Finally, the current ignorance about the properties of now three neutrinos is reviewed. PMID- 17740339 TI - Model simulation of the cretaceous ocean circulation. AB - Three-dimensional numerical ocean circulation model experiments that were designed to evaluate the circulation characteristics for the mid-Cretaceous ( approximately 100 million years ago) show that the primary direction of flow through the Tethys Ocean was eastward; in contrast, a westward flowing circumglobal Tethys current has been a consistent feature of earlier reconstructions of Cretaceous ocean circulation. The model studies demonstrate that (i) ocean circulation is sufficiently sensitive to the role of continental positions, sea level, and climate to limit the application of modern analogs to past circulations, and (ii) reconstructions based on limited biogeographic data may not provide unique surface circulation patterns. PMID- 17740340 TI - Hearing in honey bees: detection of air-particle oscillations. AB - Although the airborne sounds produced by dancing honey bees seem essential in the bees' dance communication, attempts to show directly that bees can detect airborne sounds have been unsuccessful. It is shown here that bees can in fact detect airborne sounds and that they do so by detecting air-particle movements. Most vertebrates, by contrast, detect pressure oscillations. Because all traveling sound waves have both components, either can be used in sound detection. The bees' acoustic sense appears to be sensitive enough to allow bees to detect the air-particle movements that occur within several millimeters of a sound-emitting dancer. PMID- 17740341 TI - Corn and culture in central andean prehistory. AB - The prehistoric development and spread of domesticated maize varieties in the highlands of Peru, unlike the drier coastal deserts, is little known because ancient maize remains in this area survive mainly as fragments, kernels, and cob parts. An analysis of fragmented charred maize from prehistoric households (A.D.450 to 1500) in the Mantaro Valley reveals a developmental sequence of maize varieties for Highland Peru. The evidence indicates an adoption of large kernelled maize varieties beginning in the Late Intermediate (A.D. 1000). This is centuries later than a similar change in maize, associated with the Wari expansion, that occurred in coastal areas, and indicates minimal Wari impact in the Mantaro Valley. PMID- 17740343 TI - A biomedical pioneer: otto folin. PMID- 17740342 TI - Reexamination of the Three-Dimensional Structure of the Small Subunit of RuBisCo from Higher Plants. AB - The structure of L(8)S(8) RuBisCo (where L is the large subunit and S is the small subunit) from spinach has been determined to a resolution of 2.8 angstrom by using fourfold averaging of an isomorphous electron density map based on three heavy-atom derivatives. The structure of the S subunit is different from that previously reported for the tobacco S subunit in spite of 75 percent sequence identity. The elements of secondary structure, four antiparallel beta strands and two alpha helices, are the same, but the topology and direction of the polypeptide chain through these elements differ completely. One of these models is clearly wrong. The spinach model has hydrophobic residues in the core between the alpha helices and beta sheet as well as conserved residues in the subunit interactions. The deletion of residues 49 to 62 that is present in the Anabaena sequence removes a loop region in the spinach model. The positions of three mercury atoms in the heavy-atom derivatives agree with the assignment of side chains in the spinach structure. PMID- 17740344 TI - The technological past: nuts and bolts of the past. PMID- 17740345 TI - Outpourings of lava: continental flood basalts. PMID- 17740346 TI - Evaporite geology: evaporite sedimentology. PMID- 17740347 TI - Products & materials. PMID- 17740348 TI - SYPHILIS: A PUBLIC HEALTH PROBLEM. PMID- 17740349 TI - THE SOCIAL SCIENCES AND ENGINEERING EDUCATION. PMID- 17740350 TI - THE LOG OF PALMERS DISCOVERY OF ANTARCTICA. PMID- 17740352 TI - POLLEN AND HAY FEVER. PMID- 17740351 TI - THE WATER CONTENT OF MEDUSAE. PMID- 17740353 TI - MEDICAL CLASSICS. PMID- 17740354 TI - THE INFLUENCE OF IODOACETIC ACID ON THE RESPIRATORY METABOLISM OF MAMMALIAN TISSUES. PMID- 17740355 TI - CRYSTALLINE FACTOR I. PMID- 17740356 TI - ANEURIN AND THE ROOTING OF CUTTINGS. PMID- 17740357 TI - THE PREPARATION OF ABSOLUTE ETHER. PMID- 17740358 TI - QUANTITY COLLECTING OF PLANKTONIC DIATOMS. PMID- 17740359 TI - THE USE OF CARBON DIOXIDE IN THE PREPARATION OF SILICIC ACID JELLIES. PMID- 17740360 TI - Macroevolution conference. PMID- 17740362 TI - Macroevolution conference. PMID- 17740361 TI - Macroevolution conference. PMID- 17740363 TI - Macroevolution conference. PMID- 17740364 TI - Erratum. AB - Photomicrographs of normal and sickled erythrocytes that were published in the 30 January issue(Research News, p. 469) should have been credited to the laboratory of Patricia Farnsworth, Department of Physiology, New Jersey Medical School, Newark. The photos were taken by graduate student Patricia A. Burke. PMID- 17740365 TI - Lasers in space. PMID- 17740366 TI - Lasers in space. PMID- 17740368 TI - Laboratory safety. PMID- 17740367 TI - Macroevolution conference. PMID- 17740369 TI - Geologic remote sensing. AB - Remote-sensing techniques are now being used routinely in geologic interpretation for mineral and energy exploration, plant siting, waste disposal, and the development of models for regional and continental tectonics. New spaceborne methods and associated technologies are being developed to produce data from which geologic information about large areas can be derived much more rapidly than by conventional techniques. PMID- 17740370 TI - Cabinet split on merits of grain embargo. PMID- 17740372 TI - Prior restraints recommended. PMID- 17740371 TI - EPA and industry pursue regulatory options. PMID- 17740373 TI - Science subcommittees get new chairmen. PMID- 17740374 TI - Academy hosts meeting on conservation of monuments. PMID- 17740375 TI - Budget cutters clip away at science. PMID- 17740376 TI - Air academy drops ban on sickle carriers. PMID- 17740377 TI - The tradition of hughes medical: support of superior research. PMID- 17740378 TI - Institute Loses Bid for Hughes's Billions. PMID- 17740379 TI - Matter, matter, everywhere . . PMID- 17740381 TI - Prediction of huge peruvian quakes quashed. PMID- 17740380 TI - Ethiopian Stone Tools Are World's Oldest. PMID- 17740382 TI - Origins of the modern synthesis. PMID- 17740383 TI - Enzymatic transformations. PMID- 17740384 TI - Muscle physiology. PMID- 17740385 TI - A study in paleoecology. PMID- 17740386 TI - Tupaiidae. PMID- 17740387 TI - Measurements of the volcanic plumes of mount st. Helens in the stratosphere and troposphere: introduction. PMID- 17740388 TI - Airborne studies of the emissions from the volcanic eruptions of mount st. Helens. AB - The concentrations of particles less than 10 micrometers in diameter in the ash emissions from Mount St. Helens have been more than 1000 times greater than those in the ambient air. Mass loadings of particles less than 2 micrometers in diameter were generally several hundred micrograms per cubic meter. In the ash clouds, produced by the large eruption on 18 May 1980, the concentrations of several trace gases generally were low. In other emissions, significant, but variable, concentrations of sulfur gases were measured. The 18 May eruption produced nuees ardentes, lightning flashes, and volcanic hail. PMID- 17740389 TI - Trajectories of the mount st. Helens eruption plume. AB - The plume of the major eruption of Mount St. Helens on 18 May 1980 penetrated 10 to 11 kilometers into the stratosphere, attaining heights of 22 to 23 kilometers. Wind shears rapidly converted the plume from an expanding vertical cone to a thin, slightly inclined lamina. The lamina was extruded zonally in the stratosphere as the lower part moved eastward at jet stream velocities, while the upper part slowly moved westward in the region of nonsteady transition from the westerlies to the summer stratospheric easterlies. Trajectories computed to position the NASA U-2 aircraft for sampling in the plume are described. Plume volume after 8 hours of strong volcanic emission is estimated at 2 x 10(6) cubic kilometers. Only about 1 percent of this volume is attributed to the volcano; the rest was entrained from the environment. PMID- 17740390 TI - Gaseous constituents in the plume from eruptions of mount st. Helens. AB - Measurements in the stratosphere of gaseous constituents in the plume of Mount St. Helens were obtained during five flights of the NASA U-2 aircraft between 19 May and 17 June 1980. Mixing ratios from gas chromatographic measurements on samples acquired about 24 hours after the initial eruption show considerable enhancement over nonvolcanic concentrations for sulfur dioxide (more than 1000 times), methyl chloride (about 10 times), and carbon disulfide (more than 3 times). The mixing ratio of carbonyl sulfide was comparable to nonvolcanic mixing ratios although 3 days later it was enhanced two to three times. Ion chromatography measurements on water-soluble constituents are also reported. Very large concentrations of chloride, nitrate, and sulfate ions were measured, implying large mixing ratios for the water-soluble gaseous constituents from which the anions are derived. Measurements of radon-222 present in the plume are also reported. PMID- 17740391 TI - Changes in stratospheric water vapor associated with the mount st. Helens eruption. AB - A frost point hygrometer designed for aircraft operation was included in the complement of instruments assembled for the NASA U-2 flights through the plume of Mount St. Helens. Measurements made on the 22 May flight showed the water vapor to be closely associated with the aerosol plume. The water vapor mixing ratio by mass in the plume was as high as 40 x 10(-6). This compares with values of 2 x 10(-6) to 3 x 10(-6) outside of the plume. PMID- 17740392 TI - Measurements of cloud condensation nuclei in the stratosphere around the plume of mount st. Helens. AB - Measurements of cloud condensation nuclei were made from small samples of stratospheric air taken from a U-2 aircraft at altitudes ranging from 13 to 19 kilometers. The measured concentrations of nuclei both in and outside the plume from the May and June 1980 eruptions of Mount St. Helens were higher than expected, ranging from about 100 to about 1000 per cubic centimeter active at 1 percent supersaturation. PMID- 17740393 TI - Filter measurements of stratospheric sulfate and chloride in the eruption plume of mount st. Helens. AB - Five flights of the U-2 aircraft with a filter sampler aboard were flown in the Mount St. Helens debris from 19 May to 17 June 1980. Sulfate concentrations as large as 216 times the expected background were observed. The enhancements of acid chloride vapor were considerably smaller, suggesting an insignificant increase of background values of hydrogen chloride once the plume is well mixed throughout the lower stratosphere. PMID- 17740394 TI - Trace element composition of the mount st. Helens plume: stratospheric samples from the 18 may eruption. AB - Atmospheric particulate material collected from the stratosphere in the plume of the 18 May 1980 eruption of the Mount St. Helens volcano was quite similar in composition to that of ash that fell to the ground in western Washington. However, there were small but significant differences in concentrations of some elements with altitude, indicating that the stratospheric material was primarily produced from fresh magma, not fragments of the mountain. PMID- 17740395 TI - Characterization of aerosols from eruptions of mount st. Helens. AB - Measurements of mass concentration and size distribution of aerosols from eruptions of Mount St. Helens as well as morphological and elemental analyses were obtained between 7 April and 7 August 1980. In situ measurements were made in early phreatic and later, minor phreatomagmatic eruption clouds near the vent of the volcano and in plumes injected into the stratosphere from the major eruptions of 18 and 25 May. The phreatic aerosol was characterized by an essentially monomodal size distribution dominated by silicate particles larger than 10 micrometers in diameter. The phreatomagmatic eruption cloud was multimodal; the large size mode consisted of silicate particles and the small size modes were made up of mixtures of sulfuric acid and silicate particles. The stratospheric aerosol from the main eruption exhibited a characteristic narrow single mode with particles less than 1 micrometer in diameter and nearly all of the mass made up of sulfuric acid droplets. PMID- 17740396 TI - Size distributions and mineralogy of ash particles in the stratosphere from eruptions of mount st. Helens. AB - Samples from the stratosphere obtained by U-2 aircraft after the first three major eruptions of Mount St. Helens contained large globules of liquid acid and ash. Because of their large size, these globules had disappeared from the lower stratosphere by late June 1980, leaving behind only smaller acid droplets. Particle-size distributions and mineralogy of the stratospheric ash grains demonstrate in-homogeneity in the eruption clouds. PMID- 17740397 TI - Absorption of visible radiation by aerosols in the volcanic plume of mount st. Helens. AB - Samples of particles from Mount St. Helens were collected in both the stratosphere and troposphere for measurement of the light absorption coefficient. Results indicate that the stratospheric dust had a small but finite absorption coefficient ranging up to 2 x 10(-7) per meter at a wavelength of 0.55 micrometer, which is estimated to yield an albedo for single scatter of 0.98 or greater. Tropospheric results showed similar high values of an albedo for single scatter. PMID- 17740398 TI - Measurements of the imaginary part of the refractive index between 300 and 700 nanometers for mount st. Helens ash. AB - The absorption properties, expressed as a wavelength-dependent imaginary index of refraction, of the Mount St. Helens ash from the 18 May 1980 eruption were measured between 300 and 700 nanometers by diffuse reflectance techniques. The measurements were made for both surface and stratospheric samples. The stratospheric samples show imaginary index values that decrease from approximately 0.01 to 0.02 at 300 nanometers to about 0.0015 at 700 nanometers. The surface samples show less wavelength variation in imaginary refractive index over this spectral range. PMID- 17740399 TI - Marine macrophytes as a global carbon sink. AB - Marine macrophyte biomass production, burial, oxidation, calcium carbonate dissolution, and metabolically accelerated diffusion of carbon dioxide across the air-sea interface may combine to sequester at least 10(9) tons of carbon per year in the ocean. This carbon sink may partially account for discrepancies in extant global carbon budgets. PMID- 17740400 TI - Fate and transport of dieldrin in coralville reservoir: residues in fish and water following a pesticide ban. AB - A model for the fate and transport of pesticide has been calibrated with field data from 1968 to 1978. The results have aided in a management decision to lift a commercial fishing ban in Coralville Reservoir, eastern Iowa. Dieldrin residues in fish, sediment, and water are all declining at about 15 percent per year. Approximately 50 percent of the pesticide load is exported from the reservoir in the outflow, 40 percent undergoes sedimentation, and 10 percent enters the fish. PMID- 17740401 TI - Mutualism among sessile invertebrates: a mediator of competition and predation. AB - Hydroids of the genus Zanclea are epizoic on encrusting bryozoans. The bryozoans protect these hydroids with skeletal material. Zanclea polyps on the bryozoan Celleporaria brunnea sting small predators and adjacent competitors, helping Celleporaria to survive and to grow over competing species. This mutualism enables the two species to cover a larger area than they could individually. PMID- 17740402 TI - SCIENCE NEWS. PMID- 17740403 TI - THE RADIOSENSITIVENESS OF CELLS AND TISSUES AND SOME MEDICAL IMPLICATIONS. PMID- 17740405 TI - DISCUSSION. PMID- 17740404 TI - OBITUARY. PMID- 17740407 TI - LIGHT A FACTOR IN RANCIDITY. PMID- 17740406 TI - TWISTED TREE TRUNKS ON THE GASPE PENINSULA. PMID- 17740408 TI - AN INEXPENSIVE MICROGRAPHIC PROJECTOR. PMID- 17740409 TI - THE EVOLUTION OF A CAROTID SINUS REFLEX AND THE ORIGIN OF VAGAL TONE. PMID- 17740410 TI - DEVICE FOR WASHING MICROSCOPICAL TISSUES. PMID- 17740412 TI - THE NATIONAL ACADEMY OF SCIENCES. III. PMID- 17740411 TI - A LABORATORY EXPERIMENT IN ANIMAL BEHAVIOR. PMID- 17740413 TI - Letters. PMID- 17740414 TI - Letters. PMID- 17740415 TI - Teaching physics in high school. PMID- 17740416 TI - Are tobacco taxes tyrannical? PMID- 17740417 TI - Geography favors R & d awards. PMID- 17740419 TI - Predicting occupational success. PMID- 17740418 TI - Dams take planning. PMID- 17740420 TI - Mineral Resources: Challenge or Threat?: Can technology meet our future needs for minerals and still preserve a livable environment? PMID- 17740421 TI - Teaching Effectiveness and Government Awards: Study shows that publication and government awards are good indicators of ability in teaching undergraduates. AB - Three bodies of available data at Tufts University were used in determining whether there are meaningful relationships between teaching effectiveness, publication, and the receipt of government support. A search of the literature showed that virtually all comments in the popular literature and most references in professional journals suggest that publication and receipt of support for research somehow detract from teaching performance in the classroom. The empirical data of the Tufts study do not support these previous conclusions. The students rated as their best instructors those faculty members who had published articles and who had received or were receiving government support for research. PMID- 17740423 TI - Australia: education and science are looking up "down under". PMID- 17740424 TI - Big science: tight budgets pinch some major facilities. PMID- 17740425 TI - Satellite ionosonde records: resonances below the cyclotron frequency. AB - Resonant responses observed by the topside ionosonde in the Canadian satellite Alouette II are examined. In addition to the well-known plasma resonances, several subsidiary resonances are identified below the electron cyclotron frequency. Their patterns of occurrence are not consistent with a suggested explanation of induced magnetic dipole radiation; rather they appear to result from harmonic stimulation of the plasma resonances and beat-frequency generation. PMID- 17740426 TI - Mummy cave: prehistoric record from rocky mountains of wyoming. AB - Archeological materials from 8.5 meters of deposits in a stratified rock shelter in the Absaroka Mountains near Yellowstone National Park provide a projectile point sequence and cultutral record beginning more than 9000 years ago, and include evidence of human occupation durnig the Altithermal period. PMID- 17740428 TI - Publications Received. PMID- 17740427 TI - Enzyme regulation in Mammalian tissues. PMID- 17740429 TI - Meetings & Conferences. PMID- 17740430 TI - Cooperation between Systematists and Experimental Biologists. PMID- 17740431 TI - The Atlantic Estuarine Research Society. PMID- 17740432 TI - Immigration Laws and the Foreign Visitor. PMID- 17740434 TI - R. C. Archibald and Mathematics Libraries. PMID- 17740433 TI - Fallout Dosages at Washington, D.C. AB - It has been assumed that the fission product conglomerate emits one gamma ray per beta particle throughout its lifetime. The fallout velocities are not accurately known, and in some cases the detonation and response times have been approximated. For these reasons, the dosages reported in this paper can be accurate in order of magnitude only. With these reservations, an infinity dose of 0.2 roentgen or less due to all explosions between January 1951 and May 1955 is reported for Washington, D.C. Therefore, it is probable that the total fallout from all weapons tests that have so far been conducted will produce only a fraction of the lifetime dosage due to natural radioactivity and cosmic radiation (6). Most of the dosage comes from the Nevada tests, and only a small part from the Pacific thermonuclear tests (7). Fission products contained in that part of the cloud of a thermonuclear explosion which extends above the level of precipitation is found to contribute only very slightly to the dosage at great distances. No analysis was carried out for air activity data taken at other locations, but their qualitative similarity to those taken in Washington suggests that infinity doses in most other locations in the northern hemisphere will not be greatly different. Present results are in essential agreement with two other measurements that have been reported. Eisenbud and Harley (8) have measured fallout deposited on gummed papers (9) at various locations in the United States and have found an average dose of 0.001 roentgen per year. Stewart, Crooks, and Fisher (10) have measured the activity of air, rainwater, and ground deposits in England and report an infinity dose of 0.055 roentgen. This somewhat lower figure may result from their greater distance from Nevada, which appears to be the source of most of the fallout in the United States. The authors wish to thank Dr. H. Friedman and Dr. L. B. Lockhart for their continued support and for many helpful discussions. PMID- 17740435 TI - News of Science. PMID- 17740436 TI - Marginal Homozygosity for Gene Arrangement in Drosophila robusta. PMID- 17740437 TI - Absorption and Metabolism of Iron. AB - In the article "Absorption and metabolism of iron" [Science 123, 87 (20 Jan. 1955)], the wavelength of maximum absorption of the iron-siderophilin complex was incorrectly given as 520 millimicrons. On page 89, the first sentence in the second paragraph under the heading "Iron transport" should read "The Fe+++-B(1) globulin complex has a characteristic salmon-pink color with a maximum light absorption at 460 millimicrons...." PMID- 17740439 TI - Miscellaneous Publications. PMID- 17740441 TI - SCIENCE NEWS. PMID- 17740440 TI - Scientific Meetings. PMID- 17740443 TI - MICROPHOTOGRAPHIC DUPLICATION IN THE SERVICE OF SCIENCE. PMID- 17740442 TI - RESUSCITATION WITH CARBON DIOXIDE. PMID- 17740444 TI - DISTRIBUTION OF TERMITES. PMID- 17740445 TI - HIGH ALTITUDE STRATOSPHERE OBSERVATIONS. PMID- 17740446 TI - FLOOD INJURY TO TREES. PMID- 17740447 TI - FISH MORTALITY. PMID- 17740449 TI - THE EFFECTS OF PHYSIOLOGICAL AGENTS ON ADULT TISSUES IN VITRO. PMID- 17740448 TI - PRINCIPAL DECISIONS CONCERNING NOMENCLATURE MADE BY THE SIXTH INTERNATIONAL BOTANICAL CONGRESS, AMSTERDAM (1935). PMID- 17740450 TI - BACTERIOLOGIC EXPERIMENTATION ON THE GUINEA PIG FETUS. PMID- 17740451 TI - A FURTHER IMPROVED PROSPECTING PICK. PMID- 17740452 TI - THE ISOLATION FROM COTTONSEED OIL OF AN ALCOHOL RESEMBLING ALPHA TOCOPHEROL FROM WHEAT GERM OIL. PMID- 17740453 TI - First Scientific Bureau. PMID- 17740454 TI - Science, Ethics, and Politics. PMID- 17740455 TI - News of Science. PMID- 17740456 TI - Radiocarbon Dates from Sandia Cave, Correction. PMID- 17740457 TI - Effect of Gibberellic Acid on Growth of Maize Roots. PMID- 17740458 TI - First Discovery of Marine Wood-Boring Copepods. PMID- 17740459 TI - Meetings and Societies. PMID- 17740460 TI - EQUIPMENT NEWS. PMID- 17740461 TI - This week in science. PMID- 17740462 TI - Erratum. AB - In Deborah M. Barnes's Research News article "Drug may protect brains of heart attack victims" (6 Feb., p. 632), William A. Pulsinelli (whose name was misspelled) was incorrectly included in the statement, "because rodents are more susceptible to ischemic brain damage than primates, the Cornell researchers stress the importance of testing potential neuroprotective drugs in nonhuman primates before giving them to humans." PMID- 17740463 TI - Bibliographic databases. PMID- 17740465 TI - Fredrickson takes leave from hughes. PMID- 17740464 TI - Doubt Cast on Laser Weapons: An American Physical Society report says major technical advances and at least another decade of research will be required to determine whether directed energy weapons will work. PMID- 17740466 TI - U.K. Science: Survival of the Fittest--or Fattest?: The British government claims its budget restrictions will increase the effectiveness of university research; critics say too much selectivity could kill the goose that lays the golden egg. PMID- 17740468 TI - Plutonium by the Ton: The fate of the defense production reactors hangs on the need for plutonium, and information on that is hard to find. PMID- 17740467 TI - Security Council Blocks NSF Grant to IIASA: A $500,000 grant that NSF approved 15 months ago has been turned down after a tortuous interagency review. PMID- 17740469 TI - Mit gets $3 million for news fellowships. PMID- 17740471 TI - On the Benefits of Being Eaten: Experiments on a western mountain herb, scarlet, gilia, show that its fitness is enhanced after being partially browsed. PMID- 17740470 TI - NAS Hopes to Save Issues. PMID- 17740472 TI - Statistical Traps Lurk in the Fossil Record: A combination of the skewed distribution in the species abundance and the vagaries of fossilization may suggest differences in fossil samples where no real difference exists. PMID- 17740473 TI - Supernova 1987A: Notes from All Over. AB - As Supernova 1987A in the Large Magellanic Cloud continues on its inexorable course-it has currently reached magnitude 3.3, with perhaps another magnitude of brightening to go in the next few months before it begins its long, slow fade into oblivion-astronomers are following its every step with avid interest. Some recent developments: PMID- 17740474 TI - Decision-making in the presence of risk. AB - Proposed in the 18th century by Cramer and Bernoulli and formally axiomatized in the 20th century by von Neumann and Morgenstern and others, the expected utility model has long been the dominant framework for the analysis of decision-making under risk. A growing body of experimental evidence, however, indicates that individuals systematically violate the key behavioral assumption of this model, the so-called independence axiom. This has led to the development and analysis of nonexpected utility models of decision-making. Although recent work in this area has shown that the analytical results of expected utility theory are more robust than previously supposed, other important issues remain unresolved. PMID- 17740475 TI - Accelerator mass spectrometry for measurement of long-lived radioisotopes. AB - Particle accelerators, such as those built for research in nuclear physics, can also be used together with magnetic and electrostatic mass analyzers to measure rare isotopes at very low abundance ratios. All molecular ions can be eliminated when accelerated to energies of millions of electron volts. Some atomic isobars can be eliminated with the use of negative ions; others can be separated at high energies by measuring their rate of energy loss in a detector. The long-lived radioisotopes (10)Be, (14)C,(26)A1, 36Cl, and (129)1 can now be measured in small natural samples having isotopic abundances in the range 10(-12) to 10(- 5) and as few as 10(5) atoms. In the past few years, research applications of accelerator mass spectrometry have been concentrated in the earth sciences (climatology, cosmochemistry, environmental chemistry, geochronology, glaciology, hydrology, igneous petrogenesis, minerals exploration, sedimentology, and volcanology), in anthropology and archeology (radiocarbon dating), and in physics (searches for exotic particles and measurement of halflives). In addition, accelerator mass spectrometry may become an important tool for the materials and biological sciences. PMID- 17740477 TI - SB&F Focuses on Science in the Middle Grades. PMID- 17740476 TI - Asymmetries in mating preferences between species: female swordtails prefer heterospecific males. AB - In male swordtails ((Xiphophorus nigrensis)) there are three size classes that derive from allelic variation at the pituitary locus on the Y chromosome. Progeny analysis and preference tests suggest that females prefer to mate with larger males. In the closely related X. pygmaeus, there is no allelic variation at this locus; this species consists of males similar in size only to smaller X. nigrensis males. In addition to being smaller than most X. nigrensis males, these X.pygmaeus males also lack both the swordtail and a major component of the courtship display common in most X. nigrensis males. Usually, female X. pygmaeus prefer to mate with heterospecific males rather than conspecifics, regardless of body size and the presence of a swordtail. However, the smallest X. nigrensis males lack the same courtship component as do the X. pygmaeus males, and in this comparison female X. pygmaeus show no preference. Although sexual selection, through its action on divergence of courtship displays, has been implicated as a factor leading to speciation, in this case sexual selection could lead to the congealing of gene pools between heterospecifics. PMID- 17740478 TI - Pacific division meets in san diego, 14-18 june. PMID- 17740479 TI - Reminder for members. PMID- 17740480 TI - Project on liberal education and the sciences receives funding. PMID- 17740481 TI - Obituaries. PMID- 17740482 TI - Section y adopts statement of membership and purpose. PMID- 17740483 TI - Global Crop Resources: Gene Banks and the World's Food. PMID- 17740484 TI - Mechanisms of mobility: insect flight. PMID- 17740485 TI - Deep sea data: north atlantic palaeoceanography. PMID- 17740486 TI - Astronomical influences: the galaxy and the solar system. PMID- 17740487 TI - Products & materials. PMID- 17740488 TI - THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17740489 TI - APPLIED BOTANY, RETROSPECTIVE AND PROSPECTIVE. PMID- 17740491 TI - ETHER WAVES FROM EXPLOSIONS. PMID- 17740490 TI - ECOLOGY. PMID- 17740493 TI - THE EUROPEAN POND-SNAIL. PMID- 17740492 TI - FORCE AND ENERGY. PMID- 17740494 TI - A NEW METEORITE FROM KANSAS. PMID- 17740495 TI - NOTES ON THE LAFAYETTE AND COLUMBIA FORMATIONS AND SOME OF THEIR BOTANICAL FEATURES. PMID- 17740496 TI - INSTINCT IN SONG BIRDS, METHOD OF BREEDING IN HAND-REARED ROBINS (MERULA MIGRATORIA). PMID- 17740497 TI - A NEW SHORT METHOD OF MULTIPLICATION. PMID- 17740498 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17740499 TI - MEMORIAL OF HALLER. PMID- 17740500 TI - ANDREW CARNEGIE, PATRON OF LEARNING. PMID- 17740502 TI - GEOLOGICAL MAPPING OF THE OCEAN BOTTOM. PMID- 17740503 TI - THE MAYA BREADNUT IN SOUTHERN FLORIDA. PMID- 17740501 TI - HOW CARS GO OUT OF CONTROL: ANALYSIS OF THE DRIVER'S REFLEXES. PMID- 17740504 TI - TACONIC THRUSTING AND PALEOGEOGRAPHIC BASE MAPS. PMID- 17740505 TI - SOME EUGENICAL ASPECTS OF THE INDIANS OF PISTE, YUCATAN. PMID- 17740506 TI - YALE LABORATORIES OF PRIMATE BIOLOGY, INCORPORATED. PMID- 17740508 TI - ELECTRO-ULTRA-FILTRATION APPARATUS. PMID- 17740507 TI - ILLUMINATOR FOR CRITICAL MICROSCOPY UTILIZING AUTOMOBILE HEADLIGHT LAMPS. PMID- 17740509 TI - THE UTILITY OF BROKEN AUTOMATIC PIPETTES. PMID- 17740511 TI - News of Science. PMID- 17740510 TI - No Opposition, No Support. PMID- 17740513 TI - Economics of Nuclear Power. PMID- 17740512 TI - Economics of Nuclear Power. PMID- 17740514 TI - Economics of Nuclear Power. PMID- 17740516 TI - Equipment. PMID- 17740517 TI - SOME OF THE FUNCTIONS AND FEATURES OF A BIOLOGICAL STATION. PMID- 17740518 TI - RECENT PROGRESS IN AGRICULTURAL CHEMISTRY. PMID- 17740520 TI - THE SECTION OF ANTHROPOLOGY AT ITHACA. PMID- 17740519 TI - THE MONTREAL MEETING OF THE GEOLOGICAL SOCIETY OF AMERICA. PMID- 17740521 TI - ALONZO S. KIMBALL. PMID- 17740523 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17740522 TI - CURRENT NOTES ON PHYSIOGRAPHY. PMID- 17740524 TI - THE WASHINGTON ACADEMY OF SCIENCES. PMID- 17740525 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17740526 TI - THE SWEDISH ARCTIC EXPEDITION OF 1898. PMID- 17740527 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17740528 TI - DISCUSSION AND CORRESPONDENCE. PMID- 17740529 TI - 'TIME WASTED.'. PMID- 17740530 TI - TRAVEL AND TRANSPORTATION. PMID- 17740531 TI - ZOOLOGY AT THE UNIVERSITY OF CHICAGO. PMID- 17740533 TI - A LECTURE BY REGNAULT. PMID- 17740532 TI - INFORMATION DESIRED. PMID- 17740534 TI - PROFESSOR FONTAINE AND DR. NEWBERRY ON THE AGE OF THE POTOMAC FORMATION. PMID- 17740535 TI - THE AMERICAN MORPHOLOGICAL SOCIETY. PMID- 17740536 TI - CURRENT NOTES ON PHYSIOGRAPHY. PMID- 17740537 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17740539 TI - REVUE DE MECANIQUE. PMID- 17740538 TI - NOTES ON INORGANIC CHEMISTRY. PMID- 17740540 TI - OPPORTUNITIES FOR TRAINING IN PHYSIOLOGY. PMID- 17740541 TI - PSEUDO-AURORA AGAIN. PMID- 17740542 TI - NOTE ON NATRIX GROHAMII B. & G. PMID- 17740543 TI - GREENLAND GLACIERS. PMID- 17740544 TI - Strength in Union? PMID- 17740546 TI - News of Science. PMID- 17740545 TI - Humble Oil Company Radiocarbon Dates II. PMID- 17740548 TI - Meetings and Societies. PMID- 17740547 TI - Heat Inactivation of Catalase in Deuterium Oxide. PMID- 17740549 TI - Damaging Rumor. PMID- 17740550 TI - Limited Attendance. PMID- 17740551 TI - The Sick Feeling Remains. PMID- 17740552 TI - "Living" Molecule. PMID- 17740553 TI - EQUIPMENT NEWS. PMID- 17740554 TI - A National Science Foundation. PMID- 17740555 TI - A National Science Foundation. PMID- 17740556 TI - A National Science Foundation. PMID- 17740557 TI - Programs for Medicine and National Health in the USSR. PMID- 17740558 TI - Antiseptic Action of Glycerite of Hydrogen Peroxide on Mycobacterium tuberculosis (var. hominis). PMID- 17740559 TI - Thromboplastic Properties of Penicillin and Streptomycin. PMID- 17740560 TI - Depletion of Vitamin A Reserves in the Livers of Cattle. PMID- 17740561 TI - Activity of Protein Synthesis by the Intestine. PMID- 17740562 TI - Quick Decline of Orange Trees; A Virus Disease. PMID- 17740563 TI - Lipoid Substance in the Cells of Proximal Convoluted Tubules of the Kidneys of Young Rats on a Choline-deficient Diet. PMID- 17740564 TI - A Quantitative Study of the Complement-Hemolysin Relation. PMID- 17740565 TI - Reduction in the Vital Capacity of Asthmatic Subjects Following Exposure to Aerosolized Pollen Extracts. PMID- 17740566 TI - Vacuum Infiltration as a Method for Determining Enzymic Activity in Vivo. PMID- 17740567 TI - A Method for Reclaiming Dried Zoological Specimens. PMID- 17740569 TI - Letter to the Editor. PMID- 17740570 TI - Research and Purpose. PMID- 17740568 TI - Action of Subtilin in Reducing Infection by a Seed-borne Pathogen. PMID- 17740572 TI - Productivity Measure Disputed. PMID- 17740571 TI - Manpower in Biomedical Science. PMID- 17740573 TI - Letter to the Editor. PMID- 17740574 TI - Air Pollution. PMID- 17740575 TI - Ultrahigh Vacuum: Application makes possible important advances in physics, chemistry, and engineering. PMID- 17740576 TI - The Nature of Matter: Purposes of High Energy Physics. PMID- 17740578 TI - A Defence by Victor F. Weisskopf. PMID- 17740577 TI - H. A. Bethe Discusses High Energy Physics. PMID- 17740579 TI - High Energy Physics and the Rest of Physical Science: G. C. Wick. PMID- 17740581 TI - NIH Study: Wooldridge Committee Praises Past Efforts, But Urges Major Organizational Revisions. PMID- 17740580 TI - Julian Schwinger on the Future of Fundamental Physics. PMID- 17740582 TI - Solar Boat: Army Evaluators Record a Plus for Novel Craft. PMID- 17740583 TI - Indium Telluride (II'): Transitory Intermediate Phase in the Transformation InTe(II) to InTe(I). AB - The high-pressure cubic metallic form of indium telluride, InTe(II), transforms at 1 atmosphere to a new transitory polymorph, designated InTe(II'), which, in turn, transforms to the stable tetragonal polymorph InTe(I). The new polymorph is apparently tetragonal with unit-cell dimensions a(0) = 6.06 A, c(0) = 6.55 A. The transformation rates of InTe(II) to InTe(II') and of InTe(II') to InTe(I) are dependent on both time and temperature; the former is very rapid above 60 degrees C and the latter is very rapid above 125 degrees C. PMID- 17740584 TI - Inheritance of Linoleic and Oleic Acids in Maize. AB - Gas-liquid chromatographic analysis of methyl esters of fatty acids of individual maize seeds of parental and segregating populations suggests that desaturation at the Delta(12-13) position in oleic acid is under simple Mendelian control. High linoleic acid content is recessive to low. PMID- 17740586 TI - Radiation Preservation of Foods. PMID- 17740585 TI - Mechanical Translation: U.S.-Japan Joint Conference. PMID- 17740587 TI - Vesalius Commemoration at Brussels. PMID- 17740589 TI - SECTION I--ECONOMIC AND SOCIAL SCIENCE. PMID- 17740590 TI - The Vegetation of the Lamao Forest Reserve; The Philippine Journal of Science. PMID- 17740588 TI - THE TECHNICAL SCHOOL AND THE UNIVERSITY. PMID- 17740592 TI - CORRESPONDENCE RELATING TO THE SURVEY OF THE COAL FIELDS OF ARKANSAS. PMID- 17740591 TI - 'AN IGNORED THEORY OF THE ICE AGE.'. PMID- 17740593 TI - THE PRESIDENCY OF THE MASSACHUSETTS INSTITUTE OF TECHNOLOGY. PMID- 17740595 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17740594 TI - A SIMPLE METHOD OF ILLUSTRATING UNIFORM ACCELERATION. PMID- 17740596 TI - THE PERKIN LIBRARY. PMID- 17740597 TI - RESEARCH LABORATORY OF PHYSICAL CHEMISTRY OF THE MASSACHUSETTS INSTITUTE OF TECHNOLOGY. PMID- 17740598 TI - THE BODY PHYSIOLOGIC AND THE BODY POLITIC. PMID- 17740599 TI - GLADWYN KINGSLEY NOBLE (September 20, 1894-December 9, 1940). PMID- 17740601 TI - HIGH-VOLTAGE TRANSMISSION LABORATORY AT CORNELL UNIVERSITY. PMID- 17740600 TI - THE UNION OF AMERICAN BIOLOGICAL SOCIETIES. PMID- 17740602 TI - SCIENTIFIC EXPEDITIONS. PMID- 17740603 TI - GRANTS OF THE CARNEGIE CORPORATION OF NEW YORK. PMID- 17740604 TI - THE INDUSTRIAL X-RAY UNIT OF THE GENERAL ELECTRIC COMPANY. PMID- 17740605 TI - A NEW RADIOACTIVE SERIES. PMID- 17740606 TI - PLANS FOR THE FUTURE OF THE VIRGINIA ACADEMY OF SCIENCE. PMID- 17740607 TI - A NEW RADIOACTIVE SERIES. PMID- 17740608 TI - THE PRESENTATION OF SCIENTIFIC PAPERS. PMID- 17740609 TI - THE EXCRETION OF SPECIFIC FLUORESCENT SUBSTANCES IN THE URINE IN PELLAGRA. PMID- 17740610 TI - EFFECT OF ALCOHOL ON VITAMIN A CONTENT OF BLOOD IN HUMAN SUBJECTS. PMID- 17740611 TI - ULTRAVIOLET TRANSMISSION BY THE VITELLINE MEMBRANE OF THE HEN'S EGG. PMID- 17740614 TI - SECTION F, ZOOLOGY. PMID- 17740612 TI - A SIMPLE APPARATUS FOR PRESSURE FILTRATION. PMID- 17740613 TI - AN ELECTRONIC RELAY WITH IMPROVED CHARACTERISTICS. PMID- 17740616 TI - THE NEW YORK ZOOLOGICAL PARK AND AQUARIUM. PMID- 17740617 TI - ON THE PRIMARY DIVISION OF THE REPTILIA INTO. PMID- 17740615 TI - SECTION G, BOTANY. PMID- 17740619 TI - ACCOMPLISHMENTS AND FUTURE OF THE PHYSICAL SCIENCES. PMID- 17740618 TI - ORTHOPLASY, ETC. PMID- 17740620 TI - THE CONTRIBUTIONS OF ARTHUR A. NOYES TO SCIENCE. PMID- 17740621 TI - THE EIGHTIETH ANNIVERSARY OF PROFESSOR S. N. WINOGRADSKY. PMID- 17740622 TI - MEAT DIET: BLOOD AS AN ANTISCORBUTIC FACTOR. PMID- 17740623 TI - A WHALE SHARK OFF BIMINI, BAHAMAS. PMID- 17740625 TI - THE INCIDENCE OF COLOR-BLINDNESS AMONG JEWISH MALES. PMID- 17740624 TI - SYMBOLS FOR THE ARTIFICIALLY RADIOACTIVE ELEMENTS. PMID- 17740626 TI - THE TRANSMISSIBLE AGENT IN THE ROUS CHICKEN SARCOMA NO. I. PMID- 17740628 TI - A NEW TECHNIQUE FOR PRODUCING LESIONS OF THE ENCEPHALON CORTEX. PMID- 17740627 TI - SOME EFFECTS OF ANDROGENIC SUBSTANCES IN THE RAT. PMID- 17740629 TI - FIXATION OF POTASSIUM IN SOILS. PMID- 17740630 TI - A METHOD OF MOUNTING MAPS. PMID- 17740631 TI - AN ILLUSTRATION. PMID- 17740632 TI - REVERSION IN FLORAL PARTS. PMID- 17740633 TI - PROFESSOR TAIT AND MR. HERBERT SPENCER. PMID- 17740634 TI - THE CLASSIFICATION OF SCIENCE. PMID- 17740635 TI - SIGSBEE'S GRAVITATING TRAP. PMID- 17740637 TI - REPORT OF THE DREDGING CRUISE OF THE U. S. STEAMER BLAKE, COMMANDER BARTLETT, DURING THE SUMMER OF 1880. PMID- 17740636 TI - THE DURATION OF THE ARCTIC WINTER. PMID- 17740638 TI - PERSONAL DANGER CONNECTED WITH ELECTRIC LIGHTING. PMID- 17740639 TI - DR. SIEMENS' ELECTRICAL FURNACE. PMID- 17740640 TI - DESILVERIZATION OF LEAD BY THE ZINC PROCESS. PMID- 17740641 TI - ASTRONOMY. PMID- 17740642 TI - THE TERRESTRIAL PROGRESSION OF THE BRAZILIAN "CAMBOTA," CALLICHTHYS ASPER. PMID- 17740644 TI - BOTANY. PMID- 17740643 TI - MICROSCOPY. PMID- 17740645 TI - To the Editor of science. PMID- 17740647 TI - SWIFT'S COMET. PMID- 17740646 TI - NEW COMPANION To FORNACIS. PMID- 17740648 TI - CHEMICAL NOTES. PMID- 17740649 TI - PHYSIOLOGY. PMID- 17740650 TI - PEARLS FROM THE OHIO MOUND. PMID- 17740652 TI - NORTHERN LIGHTS. PMID- 17740651 TI - THE USE OF RADIUM IN THE TREATMENT OF LEPROSY. PMID- 17740653 TI - SCRAP IRON AND DYNAMITE SUGGESTED FOR FROST PROTECTION. PMID- 17740654 TI - THE OPIUM TRAFFIC. PMID- 17740655 TI - PAPER-MILL WASTE. PMID- 17740656 TI - ORGANIZATION OF CHEMISTS IN THE UNITED STATES. PMID- 17740657 TI - OCEANIC CIRCULATION. PMID- 17740658 TI - BRAYTON HOWARD RANSOM. PMID- 17740659 TI - HENRY ROSE CARTER. PMID- 17740660 TI - THE UNDERWORLD OF SCIENCE. PMID- 17740662 TI - AVOIDABLE DIFFICULTIES WITH TERMINOLOGY IN COMPARATIVE ANATOMY. PMID- 17740661 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17740663 TI - ARITHMETIZATION IN THE HISTORY OF MATHEMATICS. PMID- 17740665 TI - A SIMPLE AND EFFICIENT HYDROGEN ELECTRODE. PMID- 17740664 TI - LUMINOUS SPIDERS. PMID- 17740666 TI - INACTIVATION OF INSULIN BY GLUCOSE WITH A COMMENT ON THE GENESIS OF DIABETES. PMID- 17740668 TI - Language, projection, and computer therapy. PMID- 17740667 TI - OBSERVATIONS ON KIDNEY FUNCTION IN NECTURUS MACULOSUS. PMID- 17740669 TI - Cloning and maternal inheritance. PMID- 17740671 TI - Equine VD: Isolating the Agent. PMID- 17740670 TI - Cloning and maternal inheritance. PMID- 17740672 TI - Technology in response to local needs. PMID- 17740673 TI - Sm-nd and rb-sr chronology of continental crust formation. AB - Samarium-neodymium and rubidium-strontium isotopic systematics together with plausible assumptions regarding the geochemical evlution of continental crust material, have been used to ascertain the times at which segments of continental crust were formed. Analyses of composites from the Canadian Shield representing portions of the Superior, Slave, and Churchill structural provinces indicate that these provinces were all formed within the period 2.5 to 2.7 aeons. It has been possible to determine the mean age of sediment provenances, as studies of sedimentary rocks suggest that the samarium-neodymium isotopic system is not substantially disturbed during sedimentation or diagenesis. PMID- 17740675 TI - Is problem of succession settled for science office at state? PMID- 17740674 TI - The physics interviewing project: a tour of interviews in Asia. AB - The Physics Interviewing Project assists graduate physics departments in evaluating foreign applicants. Supported by some 20 universities, two interviewers, both working scientists, travel abroad and interview students individually for about 1 hour each. Prospective teaching assistants are rated on physics knowledge, problem-solving ability, and English language proficiency. Ratings on all interviewees are sent to all supporting schools and other schools as requested. The Project aids able students from countries that have no physics Ph.D. programs (Indonesia, Malaysia, Thailand) to obtain assistantships and Ph.D.'s abroad, assists in the technological development of those countries, and helps U.S. schools in selecting the most promising foreign candidates. A similar program should be beneficial in other sciences. PMID- 17740676 TI - New study of land-based aircraft questions need for aircraft carriers. PMID- 17740677 TI - Handler protests orlov trial. PMID- 17740678 TI - New vaccine may bring man and chimpanzee into tragic conflict. PMID- 17740679 TI - Congress reluctant to seek other worlds. PMID- 17740680 TI - A new career for Norman cousins. PMID- 17740681 TI - Holistic health concepts gaining momentum. PMID- 17740682 TI - Erratum. AB - In the report by C. W. McCutchen [197, 691 (1977)], the sentence in paragraph 2, column 3, "The downward motion is an inversion of the upward motion about a point on the axis of samara spin" is in error. It should be replaced by "The downward motion is a reflection of the upward motion successively in a horizontal and in a vertical plane." PMID- 17740683 TI - Changing profile of deep-sea miners. PMID- 17740684 TI - New Light on Quasars: Unraveling the Mystery of BL Lacertae. PMID- 17740686 TI - Seventh interciencia symposium to focus on arid lands. PMID- 17740685 TI - Particle physics: new evidence from Germany for fifth quark. PMID- 17740687 TI - Board adopts annual meeting conduct statement. PMID- 17740688 TI - R & d colloquium. PMID- 17740689 TI - Women's Education Survey Announced. PMID- 17740690 TI - For the library. PMID- 17740691 TI - An ancient conundrum. PMID- 17740692 TI - Brain structure and function. PMID- 17740694 TI - Isotopic variations in space. PMID- 17740693 TI - Foraging in primates. PMID- 17740695 TI - Lancefield swamp and the extinction of the Australian megafauna. AB - Excavations into the Australian swamp of Lancefield show that a bone bed dated at 26,000 years ago contains perhaps 10,000 giant extinct animals. Associated artifacts suggest that humans were in the area, but the direct cause of death of the animals is, on present evidence, not explicable. Such a recent date for the classic megafauna shows that it was living together with humans for at least 7000 years in southeast Australia. This enduring association argues against a catastrophic and rapid overkill in the Australian Pleistocene. PMID- 17740696 TI - Atomic hydrogen on Mars: measurements at solar minimum. AB - The Copernicus Orbiting Astronomical Observatory was used to obtain measurements of Mars Lyman-alpha (1215.671-angstrom) emission at the solar minimum, which has resulted in the first information on atomic hydrogen concentrations in the upper atmosphere of Mars at the solar minimum. The Copernicus measurements, coupled with the Viking in situ measurements of the temperature (170 degrees +/- 30 degrees K) of the upper atmosphere of Mars, indicate that the atomic hydrogen number density at the exobase of Mars (250 kilometers) is about 60 times greater than that deduced from Mariner 6 and 7 Lyman-alpha measurements obtained during a period of high solar activity. The Copernicus results are consistent with Hunten's hypothesis of the diffusion-limited escape of atomic hydrogen from Mars. PMID- 17740697 TI - Winter rain and summer ozone: a predictive relationship. AB - Insights from dendrochronology have provided a new seasonal predictor for air pollution meteorology. In the San Francisco Bay Area summer ozone excesses over the federal ozone standard are correlated (correlation coefficient r = .87) with precipitation for the two preceding winters, a factor related to tree-ring width in a precipitation-stressed climate. The hypothesis that reactive hydrocarbon emissions from vegetative biomass affects these ozone excesses was supported by a similar correlation between summer hydrocarbon average maximums and the two winter precipitation factor, reaching r = .88 at suburban stations. A weak tendency for hot summers to follow wet winters (in 16 years of California data) explains only a minor part of the ozone-rain relationship in multiple correlations. PMID- 17740698 TI - Degraded lignin compounds identified in silicified wood 200 million years old. AB - Degraded lignin compounds have been identified in Triassic age (about 200 million years) silicified wood from the Petrified Forest National Park in Arizona. The pyrolysis products from black carbonaceous samples include carbon dioxide, low molecular-weight alkanes and alkenes, benzene, alkyl-substituted benzenes, phenol, cresol, xylenols, indenes, benzofurans, trimethylindanone, and naphthalenes. These compounds are also the primary pyrolyzates of modern lignin above 500 degrees C. PMID- 17740699 TI - Recovery and maintenance of live amphipods at a pressure of 580 bars from an ocean depth of 5700 meters. AB - Amphipods were collected from an ocean depth of 5700 meters in a windowed pressure-retaining trap, kept alive in the trap for as long as 9 days aboard ship, and transported to a land laboratory. Observations suggest that the animals can easily tolerate decompressions of 29 percent and briefly of 70 percent of the value of 580 bars, the pressure of their natural habitat. The average pleopod beat frequency was 106 beats per minute. Evidence suggests that food (fish bait) can have at least a 4-day residence time in the gut of these animals. PMID- 17740700 TI - Mineralization kinetics: a constant composition approach. AB - A new method is described for studying, reproducibly, the kinetics of crystallization of minerals under conditions of constant solution composition even at very low supersaturations. For calcium phosphates the method provides direct evidence for octacalcium phosphate as the precursor to hydroxyapatite precipitation at physiological pH. PMID- 17740701 TI - Land floras: the major late phanerozoic atmospheric carbon dioxide/oxygen control. AB - Since at least the late Mesozoic, the abundance of terrestrial vegetation has been the major factor in atmospheric carbon dioxideloxygen fluctuations. Of modern ecosystem types occupying more than 1 percent of the earth's surface, productivity/area ratios of terrestrial ecosystems (excepting tundra and alpine meadow, desert scrub, and rock, ice, and sand) exceed those of marine ecosystems and probably have done so for much of late Phanerozoic time. Reduction of terrestrial ecosystems during marine transgression would decrease the world primary productivity, thus increasing the atmospheric carbon dioxide concentration and decreasing the oxygen concentration. Regression would produce opposite effects. PMID- 17740702 TI - Scanning electron microscope study of early lichen synthesis. AB - In the early stages of cellular interaction between the symbionts of Lecidea albocaerulescens, the phycobiont produced an extracellular sheath which bound to it hyphae of the mycobiont. Such a sheath may be a means by which the symbionts recognize each other. Hyphae of the mycobiont formed flattened appressoria as they grew over the algal cells and in this way secured the autotrophic population necessary for the development of a lichen thallus. PMID- 17740704 TI - A CHAPTER IN THE HISTORY OF MATHEMATICS. PMID- 17740703 TI - Search image for leaf shape in a butterfly. AB - The butterfly Battus philenor forms search images for leaf shape when searching for its two larval host plants in southeast Texas. This behavior increases the rate of discovery of host plants and permits females to track changes in relative host plant suitability for larval growth. Apostatic selection resulting from search image formation is a likely explanation for divergence in leaf shape by the two host plants. PMID- 17740705 TI - EIMER'S EVOLUTION OF BUTTERFLIES. PMID- 17740706 TI - PROGRESS OF PROFESSOR KITASATO'S INSTITUTE FOR INFECTIOUS DISEASES AT TOKIO. PMID- 17740707 TI - NINTH ANNUAL MEETING OF THE ASSOCIATION OF ECONOMIC ENTOMOLOGISTS, DETROIT, MICH., AUG. 12-13, 1897. PMID- 17740708 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17740709 TI - NOTES ON INORGANIC CHEMISTRY. PMID- 17740711 TI - This week in science. PMID- 17740710 TI - METEOROLOGICAL OBSERVATIONS DURING AN ATLANTIC VOYAGE. PMID- 17740712 TI - Confidence in science. PMID- 17740713 TI - Teraflop computers. PMID- 17740714 TI - Paleoanthropological contexts. PMID- 17740715 TI - Corrections and clarifications. AB - The photograph accompanying the News item "MIT techies help keep the America's Cup" (Random Samples, 29 May, p. 1277) shows the boat Stars and Stripes, not America(3), as was stated in the caption. PMID- 17740716 TI - Clear vision. PMID- 17740717 TI - Healthy museum. PMID- 17740718 TI - Sciencescope. PMID- 17740719 TI - Progress on other fronts. PMID- 17740720 TI - A scramble for data on arctic radioactive dumping. PMID- 17740722 TI - A match made in laser heaven. PMID- 17740721 TI - Trapping particles of darkness. PMID- 17740723 TI - The earliest mass extinction? PMID- 17740724 TI - Journal-istic Guidelines. PMID- 17740725 TI - Not merely academic. PMID- 17740727 TI - Small comets/big flap. PMID- 17740726 TI - The perils of a deeply held point of view. PMID- 17740728 TI - Conflicting views: the readers respond. PMID- 17740729 TI - Structural processes at slow-spreading ridges. AB - Slow-spreading (<35 millimeters per year) mid-ocean ridges are dominated by segmented, asymmetric, rifted depressions like continental rifts. Fast-spreading ridges display symmetric, elevated volcanic edifices that vary in shape and size along axis. Deep earthquakes, major normal faults, and exposures of lower crustal rocks are common only along slow-spreading ridges. These contrasting features suggest that mechanical deformation is far more important in crustal formation at slow-spreading ridges than at fast-spreading ridges. New seismic images suggest that the nature and scale of segmentation of slow-spreading ridges is integral to the deformational process and not to magmatic processes that may control segmentation on fast-spreading ridges. PMID- 17740730 TI - Transfer of biologically derived nanometer-scale patterns to smooth substrates. AB - Atomic force microscopy has been used to measure the surface profile of a periodic array of 10-nanometer (nm)-diameter holes fabricated by fast-atom beam milling of a smooth graphite surface in which a 3.5-nm-thick titanium oxide screen was used as a mask. The nanostructured titanium oxide mask was itself derived from a protein crystal template. Pattern transfer from the biological crystal to the metal oxide film and finally to the graphite substrate was accomplished entirely by parallel processing. PMID- 17740731 TI - Sea-surface temperature from coral skeletal strontium/calcium ratios. AB - Seasonal records of tropical sea-surface temperature (SST) over the past 10(5) years can be recovered from high-precision measurements of coral strontium/calcium ratios with the use of thermal ionization mass spectrometry. The temperature dependence of these ratios was calibrated with corals collected at SST recording stations and by (18)O/(16)O thermometry. The results suggest that mean monthly SST may be determined with an apparent accuracy of better than 0.5 degrees C. Measurements on a fossil coral indicate that 10,200 years ago mean annual SSTs near Vanuatu in the southwestern Pacific Ocean were about 5 degrees C colder than today and that seasonal variations in SST were larger. These data suggest that tropical climate zones were compressed toward the equator during deglaciation. PMID- 17740732 TI - Maintenance of strong rotational winds in venus' middle atmosphere by thermal tides. AB - The cloud-level atmosphere of Venus takes little more than 4 days to complete one rotation, whereas the solid planet below has a 243-day period. Computer simulations of the circulation of the Venus middle atmosphere between 40 and 85 kilometers, as driven by solar radiation absorbed in the clouds, reproduce (i) the observed cloud-level rotation rate, (ii) strong vertical shears above and below the cloud tops, and (iii) midlatitude jets and strong poleward flow on the day side. Simulated circulations converge to yield nearly the same zonal winds when initialized with both stronger or weaker rotation rates. These results support the hypothesis that the observed cloud-top rotation rate is maintained by statistical balance between fluxes of momentum by thermal tides and momentum advection by mean meridional circulation. PMID- 17740733 TI - Elasticity of agr-Cristobalite: A Silicon Dioxide with a Negative Poisson's Ratio. AB - Laser Brillouin spectroscopy was used to determine the adiabatic single-crystal elastic stiffness coefficients of silicon dioxide (SiO(2)) in the alpha cristobalite structure. This SiO(2) polymorph, unlike other silicas and silicates, exhibits a negative Poisson's ratio; alpha-cristobalite contracts laterally when compressed and expands laterally when stretched. Tensorial analysis of the elastic coefficients shows that Poisson's ratio reaches a maximum value of -0.5 in some directions, whereas averaged values for the single-phased aggregate yield a Poisson's ratio of -0.16. PMID- 17740734 TI - A wizard of arcanery. PMID- 17740735 TI - Models of vision. PMID- 17740737 TI - A Peptide. PMID- 17740736 TI - Perspectives on the sun. PMID- 17740738 TI - Products & materials. PMID- 17740739 TI - THE TERMINOLOGY OF SEAWEED COLLOIDS. PMID- 17740740 TI - THE INTERNATIONAL COMMISSION ON ZOOLOGICAL NOMENCLATURE. PMID- 17740741 TI - MILO HERRICK SPAULDING. PMID- 17740742 TI - NEW FLUID MECHANICS LABORATORY AT SYRACUSE UNIVERSITY. PMID- 17740743 TI - ANNIVERSARY OF THE ACADEMY OF SCIENCES OF THE U.S.S.R. PMID- 17740744 TI - CHAPTERS OF THE SOCIETY OF THE SIGMA XI. PMID- 17740745 TI - ANTHONY ASKHAM, THE AUTHOR OF THE VOYNICH MANUSCRIPT. PMID- 17740746 TI - THE GENETIC ASPECTS OF THE ENZYME-VIRUS THEORY OF CANCER. PMID- 17740747 TI - "ANGRY" MOSQUITOES. PMID- 17740749 TI - PRESSURE DUE TO MOUNTING SCIENTIFIC KNOWLEDGE. PMID- 17740748 TI - THE EFFECT OF OXALATES IN THE DIET. PMID- 17740750 TI - THE SHORTAGE OF SCIENTIFIC PERSONNEL. PMID- 17740751 TI - CRYSTALLINE REINECKATES OF STREPTOTHRICIN AND STREPTOMYCIN. PMID- 17740752 TI - CHRONIC INTERMITTENT ANOXIA AND IMPAIRMENT OF PERIPHERAL VISION. PMID- 17740753 TI - INHIBITION OF GROWTH OF MYCOBACTERIUM TUBERCULOSIS BY A MOLD PRODUCT. PMID- 17740754 TI - SULFONAMIDES AND EGG-SHELL FORMATION IN THE DOMESTIC FOWL. PMID- 17740755 TI - ORAL PENICILLIN WITH BASIC ALUMINUM AMINOACETATE. AB - This method appears to be suitable for the oral administration of penicillin. Basic aluminum aminoacetate seems admirably suited for this purpose. It is neutral and buffers gastric acidity to pH 4 to 4.5. While this work was in progress McDermott et al.(6) successfully employed magnesium trisilicate in this manner. Clinical work is now in progress using the combination in infections known to be susceptible to parenteral penicillin therapy. PMID- 17740756 TI - THE SOLUTION OF SOIL MINERALS IN DILUTE ACIDS. AB - Montmorillonite goes readily into solution in slightly acid water. In strong acids only bases, in pure water only free silica is removed. In the range from 0.02 to 0.5 per cent. acid, both bases and silica go into solution and recombine as an aluminosilicate sol and as highly soluble salts. The sol recovered by evaporation, washing and drying is an amorphous colloid near pyrophyllite in composition, Al(2)O(3).mSiO(2).nH(2)O, with m averaging 4.1 (3.9 to 4.5) and n about 1.5. The slight variation in m is unrelated to either sol, acid or clay concentration. A general characteristic relation between the amount of sol formed and the amounts of clay, acid and water used has been found for montmorillonite clays. This relation differs in two essential properties from that previously deduced for halloysite-allophane solutions. The variation with temperature of the constants of these equations remains to be investigated. PMID- 17740757 TI - CORNEAL VASCULARIZATION IN RATS ON A TRYPTOPHANE DEFICIENT DIET. PMID- 17740758 TI - A SIMPLIFIED METHOD FOR THE ASSAY OF ANTIBIOTICS. PMID- 17740760 TI - This week in science. PMID- 17740759 TI - SEPARATORY FUNNELS AS EXPERIMENTAL CHAMBERS IN STUDIES OF INSECT PHYSIOLOGY. PMID- 17740761 TI - The AAAS Observer. PMID- 17740762 TI - Advice on a science adviser. PMID- 17740763 TI - Science and the Party Platforms: Thanks to direct input from scientists in the drafting process, the Republican platform contains detailed proposals for science; the Democratic platform offers few specifics. PMID- 17740764 TI - The SSC and the Environment. PMID- 17740765 TI - Journals no longer censored. PMID- 17740766 TI - A Biotech Enterprise Soviet Style: The enterprise is part of a larger experiment in Soviet science under Gorbachev to spur industrial innovation in the nation. PMID- 17740767 TI - A minor identify crisis. PMID- 17740768 TI - Du Pont Stakes Claim on Superconductor Rights: A fight looms over patent rights to the first high-temperature superconductor, as several companies hope to develop the material. PMID- 17740769 TI - Britain to set science, math goals for kids. PMID- 17740770 TI - Pay Cap for Grantees Has Up Side for NSF. PMID- 17740771 TI - How Many Ways Can Halley Spin?: As astronomers await a prolonged view of Halley's bare nucleus, new evidence supports its rapid rotation and slow wobble as an explanation of its odd behavior. PMID- 17740772 TI - Another asteroid has tured comet. PMID- 17740773 TI - Computer-Drawn Pictures Stalk the Wild Trajectory: Even simple systems can exhibit chaotic behavior, but tracking them mathematically can be tricky; computer-generated pictures can help in the pursuit. PMID- 17740774 TI - Fatal attractions? PMID- 17740776 TI - Can't Stand Up for Falling Down. PMID- 17740775 TI - Required reading. PMID- 17740777 TI - Adopt a scientist. PMID- 17740778 TI - Science and the democrats. PMID- 17740779 TI - Limits on nuclear materials for arms reduction: complexities and uncerainties. PMID- 17740780 TI - The tritium factor as a forcing function in nuclear arms reduction talks. PMID- 17740781 TI - Desiccation of the aral sea: a water management disaster in the soviet union. AB - The Aral Sea in the Soviet Union, formerly the world's fourth largest lake in area, is disappearing. Between 1960 and 1987, its level dropped nearly 13 meters, and its area decreased by 40 percent. Recession has resulted from reduced inflow caused primarily by withdrawals of water for irrigation. Severe environmental problems have resulted. The sea could dry to a residual brine lake. Local water use is being improved and schemes to save parts of the sea have been proposed. Nevertheless, preservation of the Aral may require implementation of the controversial project to divert water from western Siberia into the Aral Sea basin. PMID- 17740782 TI - Chemistry of the metal-polymer interfacial region. AB - In many polymer-metal systems, chemical bonds are formed that involve metal oxygen-carbon complexes. Infrared and Mossbauer spectroscopic studies indicate that carboxylate groups play an important role in some systems. The oxygen sources may be the polymer, the oxygen present in the oxide on the metal surface, or atmospheric oxygen. Diffusion of metal ions from the substrate into the polymer interphase may occur in some systems that are cured at elevated temperatures. It is unclear whether a similar, less extensive diffusion occurs over long time periods in systems maintained at room temperature. The interfacial region is dynamic, and chemical changes occur with aging at room temperature. Positron annihilation spectroscopy may have application to characterizing the voids at the metal-polymer interface. PMID- 17740783 TI - Bulk Superconductivity at 122 K in T1(Ba,Ca)2Ca3Cu4O10.5+8 with Four Consecutive Copper Layers. AB - The observed increase of superconducting transition temperature (T(c)) with the number of copper oxide planes continues in the four-[CuO(2)](-2) layer (single TI layer) oxide superconductor, which has been prepared with > 80% purity and was magnetically aligned for crystallographic identification. A master scaling curve is proposed, which ties together the T(c)'s of virtually all known Bi and Tl oxide superconductors, and shows that the Tl(Bi) layers play an essential role in the superconductivity. publication 350 of the Barnett Institute. PMID- 17740784 TI - Femtosecond clocking of the chemical bond. AB - When a chemical bond is broken in a direct dissociation reaction, the process is so rapid that it has generally been considered instantaneous and thus unmeasurable. However, the bond does persist for times on the order of 10(-13) seconds after the photon has been absorbed. Femtosecond (10(-15) second) laser techniques can be used to directly clock this process, which describes the dynamics of the chemical bond. The time required to break the chemical bond in an elementary reaction has been measured and the characteristic repulsion length for the potential governing fragment separation has been obtained. PMID- 17740785 TI - Gibberellins: a phytohormonal basis for heterosis in maize. AB - Four commercially important maize parental inbreds and their 12 F(1) hybrids were studied to investigate the role of the phytohormone gibberellin (GA) in the regulation of heterosis (hybrid vigor). All hybrids grew faster than any inbred. In contrast, all inbreds showed a greater promotion of shoot growth after the exogenous application of GA(3). Concentrations of endogenous GA(1), the biological effector for shoot growth in maize, and GA(19), a precursor of GA(1), were measured in apical meristematic shoot cylinders for three of the inbreds and their hybrids by gas chromatography-mass spectrometry with selected ion monitoring; deuterated GAs were used as quantitative internal standards. In 34 of 36 comparisons, hybrids contained higher concentrations of endogenous GAs than their parental inbreds. Preferential growth acceleration of the inbreds by exogenous GA(3) indicates that a deficiency of endogenous GA limits the growth of the inbreds and is thus a cause of inbreeding depression. Conversely, the increased endogenous concentration of GA in the hybrids could provide a phytohormonal basis for heterosis for shoot growth. PMID- 17740786 TI - Genome size in conodonts (chordata): inferred variations during 270 million years. AB - DNA is too unstable to be preserved during fossilization, but it still seems possible to infer the genome content of fossils because in every group of organisms investigated cell size is proportional to quantity of DNA. Accordingly, information on macroevolutionary trends in genome size through millions of years is potentially available. This survey of inferred variation in genome content in fossils is based on measurements of epithelial cells in extinct conodonts over a period of 270 million years. Why genome size varies so widely amongst living organisms is a subject of continuing debate. Paleontology offers a distinct temporal perspective, but lack of data on conodont paleoecology make the proposed adaptive explanations for genome variation difficult to test. PMID- 17740787 TI - Response: do short-term tests predict rodent carcinogenicity? PMID- 17740788 TI - 4th Annual AAAS Forum for School Science: Science Teaching Making the System Work. PMID- 17740789 TI - Wildlife ecologist: aldo leopoid. PMID- 17740790 TI - Nucleosynthesis in stars: cauldrons in the cosmos. PMID- 17740791 TI - Research in neuroscience: fidia research foundation neuroscience award lectures. PMID- 17740792 TI - Some Other Books of Interest: Kelvin's Baltimore Lectures and Modern Theoretical Physics. PMID- 17740793 TI - Some other books of interest: instruments and experiences. PMID- 17740794 TI - Some other books of interest: tributes to paul dirac. PMID- 17740795 TI - Products & materials. PMID- 17740796 TI - HENRY BARKER HILL. PMID- 17740797 TI - THE STATUS OF PUBLIC MUSEUMS IN THE UNITED STATES. PMID- 17740798 TI - MONTANA AS A FIELD FOR AN ACADEMY OF SCIENCES, ARTS AND LETTERS. PMID- 17740799 TI - A TROPICAL MARINE LABORATORY FOR RESEARCH. PMID- 17740800 TI - THE PHYSICAL BASIS OF COLOR. PMID- 17740801 TI - SURFACE TENSION; MOLECULAR FORCES. PMID- 17740802 TI - NOTES ON THE JUDITH RIVER GROUP. PMID- 17740803 TI - THE OVERSPUN STRING. PMID- 17740804 TI - SEEDS BURIED IN THE SOIL. PMID- 17740805 TI - MUSEUM NOTES. PMID- 17740807 TI - THE AMERICAN MUSEUM OF NATURAL HISTORY. PMID- 17740806 TI - SOME NEW GENERIC NAMES OF MAMMALS. PMID- 17740808 TI - Crystalline Structure and Surface Reactivity: Atomistic models are unique tools for dealing with the chemical and physical properties of surfaces. AB - The role of crystalline structure in the surface reactivity of predominantly covalent materials has been examined in terms of chemical bonding concepts. In this context a solid surface can be viewed as a giant lattice defect characterized by dangling bonds. Although it is difficult, at the present stage of development of the quantum mechanical approach to surfaces, to define precisely the perturbations resulting from the abrupt termination of the lattice at the surface, a host of experimental observations can be understood by assuming displacements of surface atoms and distortions of bonding configurations in accordance with simple chemical bonding principles. A purely atomistic approach has been shown to account not only for the chemical behavior but also for certain structural and electrical characteristics of the surfaces considered. A number of phenomena, such as crystal growth and the behavior of certain lattice defects (for example, dislocations), are intimately related to the presence of dangling bonds and the associated distortions of the lattice at the surface (32). PMID- 17740809 TI - Navy's Big Dish: Zooming Costs. Reduced Need, Bring End to Plans for Biggest Radio Telescope. PMID- 17740810 TI - Tobacco and Health: PHS Sets Up Rules for Study Committee. PMID- 17740811 TI - Electrical Activity in Single Myocardial Cells of Limulus polyphemus. AB - Single cells of the heart of Limulus were examined in situ with conventional microelectrodes. Resting and action potentials were measured in a total of 20 animals, with 25 penetrations per heart during normal spontaneous activity. Resting-potential values averaged 45 millivolts. Action potentials showed a rapid upstroke and a prolonged plateau. A small, irregular burst of electrical activity occurred during the plateau phase, a discharge presumably associated with the "neurogenic" character of the heartbeat. There was no significant overshoot, nor was there any topographical localization of action-potential "types.". PMID- 17740812 TI - Repeated Homing Exhibited by a Female Pallid Bat. AB - A pallid bat (Antrozous pallidus) returned home from eight consecutive releases from six distinctly different directions and from distances ranging from 21 to 68 miles. This performance indicates that chance alone cannot be a major factor in homing, and that certain abilities possessed by this bat, and not simply randomness, must have been in operation. PMID- 17740813 TI - An Artifact in Plant Autoradiography. AB - An artifact in autoradiography of bean plants containing phosphorus-32 is reported. It was shown that the apparent accumulation of isotope in primary leaves that were oven-dried prior to exposure to x-ray films was not metabolic but due to a drying gradient occuring within the leaf. This artifact disappears when autoradiographs are made of leaves that have been freeze-dried under vacuum. PMID- 17740815 TI - Forthcoming Events. PMID- 17740814 TI - Mouse Mammary Tumor Virus. PMID- 17740817 TI - JOHN BELL HATCHER. PMID- 17740816 TI - THE MOSELY EDUCATIONAL COMMISSION. PMID- 17740818 TI - THE METRIC SYSTEM. PMID- 17740819 TI - HONORARY DEGREES IN ENGINEERING. PMID- 17740820 TI - AUTOTOMY, REGENERATION AND NATURAL SELECTION. PMID- 17740821 TI - 'PTERIDOSPERMAPHYTA.'. PMID- 17740823 TI - NOTES ON ENTOMOLOGY. PMID- 17740822 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17740824 TI - THE INTERNATIONAL ELECTRICAL CONGRESS. PMID- 17740826 TI - A NEW ELECTRIC TRANSFER-TABLE. PMID- 17740825 TI - AMERICAN AND GERMAN UNIVERSITIES. PMID- 17740827 TI - ASIA. PMID- 17740828 TI - MENTAL SCIENCE. PMID- 17740829 TI - GASTRIC JUICE AS A GERMICIDE. PMID- 17740831 TI - THE FATE OF CADAVERIC MICROBES. PMID- 17740830 TI - RECENT SAVING OF LIFE IN MICHIGAN. PMID- 17740833 TI - HEALTH MATTERS. PMID- 17740832 TI - EUROPEAN INFANTILE MORTALTY. PMID- 17740834 TI - The June Drought in the Rocky Mountain Region. PMID- 17740835 TI - Supposed Aboriginal Fish-Weirs in Naaman's Creek, near Claymont, Del. PMID- 17740836 TI - INDUSTRIAL NOTES. PMID- 17740837 TI - The Fiske Range-Finder. PMID- 17740838 TI - The advent of menopause. PMID- 17740839 TI - Response: the advent of menopause. PMID- 17740841 TI - Programmed cell death. PMID- 17740840 TI - Programmed cell death. PMID- 17740842 TI - Response: programmed cell death. PMID- 17740843 TI - Calcification rates in corals. PMID- 17740845 TI - Response: calcification rates in corals. PMID- 17740844 TI - Calcification rates in corals. PMID- 17740846 TI - SIGNALLING THROUGH SPACE WITHOUT WIRES. PMID- 17740847 TI - CHARACTERS, CONGENITAL AND ACQUIRED. PMID- 17740848 TI - THE DESIRABILITY AND THE FEASIBILITY OF THE ACQUISITION OF SOME REAL AND ACCURATE KNOWLEDGE OF THE BRAIN BY PRE-COLLEGIATE SCHOLARS. PMID- 17740849 TI - THE NATIVE DAHLIAS OF MEXICO. PMID- 17740850 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17740851 TI - THE NEW YORK STATE SCIENCE TEACHERS' ASSOCIATION. PMID- 17740853 TI - THE PROTECTION OF THE SEA OTTER. PMID- 17740852 TI - THE ROYAL SOCIETY. PMID- 17740854 TI - A NATIONAL DEPARTMENT OF HEALTH. PMID- 17740855 TI - THE UNITED STATES FISH COMMISSION. PMID- 17740856 TI - A NATIONAL DEPARTMENT OF HEALTH. PMID- 17740858 TI - ROYAL SOCIETY CONVERSAZIONE. PMID- 17740857 TI - FUNCTIONS OF TECHNICAL SCIENCE IN EDUCATION FOR BUSINESS AND THE PROFESSIONS. PMID- 17740859 TI - THE PROPOSED BIOLOGICAL STATION AT THE TORTUGAS. PMID- 17740860 TI - THE REACTIONS OF PARAMOEligCIA AND OTHER PROTOZOA TO CHEMICAL AND ELECTRICAL STIMULI. PMID- 17740861 TI - ON THE STRUCTURE OF THE PLESIOSAURIAN SKULL. PMID- 17740862 TI - NOTES ON ENTOMOLOGY. PMID- 17740864 TI - THE SOUTH AFRICAN ASSOCIATION. PMID- 17740863 TI - THE HARPSWELL LABORATORY. PMID- 17740865 TI - SCIENCE NEWS. PMID- 17740866 TI - WHAT DOES EINSTEIN MEAN? PMID- 17740867 TI - PHYSIOLOGICAL TIME. PMID- 17740869 TI - VIRGINIA GEOLOGICAL SURVEY FIELD WORK. PMID- 17740868 TI - A SUBMERGED BEACH OFF BERMUDA. PMID- 17740870 TI - POSITION OF WOOD IN BEAVER DAMS. PMID- 17740872 TI - POISONING RODENTS--AND THEN? PMID- 17740871 TI - TREATMENT FOR POISONING BY "POISON IVY". PMID- 17740873 TI - TESTING THE REACTION OF DISTILLED WATER. PMID- 17740874 TI - APPARATUS FOR OBSERVATION OF A SMALL OBJECT WHILE FLOODED WITH VARIOUS SOLUTIONS. PMID- 17740875 TI - A METHOD OF COPYING KYMOGRAPHIC RECORDS. PMID- 17740876 TI - THE NATIONAL ACADEMY OF SCIENCES. III. PMID- 17740877 TI - A SIMPLE DEVICE FOR HOLDING ULTRAFILTRATION MEMBRANES. PMID- 17740878 TI - VITAMIN B. PMID- 17740879 TI - THE CANCER GERM THEORY. PMID- 17740880 TI - PREHISTORIC REMAINS IN FLORIDA. PMID- 17740881 TI - FIREPROOF GAS TANKS. PMID- 17740882 TI - PLAN FOR THE ELECTRIFICATION OF PALESTINE. PMID- 17740883 TI - METHANOL. PMID- 17740884 TI - REST PERIODS FOR FACTORY WORKERS. PMID- 17740885 TI - THE LOS ANGELES MEETING OF THE AMERICAN CHEMICAL SOCIETY. PMID- 17740886 TI - SERVICE OF THE AMERICAN CHEMICAL SOCIETY TO THE NATION. PMID- 17740888 TI - WALTER SCOTT HENDRIXSON. PMID- 17740887 TI - THE TWILIGHT ZONE OF MATTER. PMID- 17740889 TI - THE CONDITION OF BIOLOGICAL LITERATURE IN PARIS. PMID- 17740890 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17740891 TI - ANALYZED SOUND. PMID- 17740892 TI - LOSS OF VIRULENCE IN FUNGI. PMID- 17740893 TI - "BAR SINISTER". PMID- 17740894 TI - SPONGILLA LACUSTRIS IN MASSACHUSETTS: A CORRECTION. PMID- 17740895 TI - MUSCULAR FIXATION OF THE STUTTERER'S VOICE UNDER EMOTION. PMID- 17740896 TI - RADIO-ACTIVITY AND THE PERIODIC SYSTEM. PMID- 17740897 TI - SOME FALLACIES IN THE ARGUMENTS AGAINST FULL-TIME CLINICAL INSTRUCTION. PMID- 17740899 TI - FRANK OLIN MARVIN. PMID- 17740900 TI - THE CHEMICAL INDUSTRY IN GREAT BRITAIN. PMID- 17740898 TI - CHARLES E. BESSEY. PMID- 17740901 TI - INTERSTATE CONFERENCE ON CEREAL INVESTIGATIONS. PMID- 17740902 TI - THE HARPSWELL LABORATORY. PMID- 17740903 TI - THE FUNDAMENTAL EQUATION OF DYNAMICS. PMID- 17740904 TI - THE NEW GLACIER PARK. PMID- 17740906 TI - NOTES ON ENTOMOLOGY. PMID- 17740905 TI - THE NATURE OF THE ULTIMATE MAGNETIC PARTICLE. PMID- 17740907 TI - A CASE OF ASSUMPTION OF MALE SECONDARY SEX CHARACTERS BY A COW. PMID- 17740909 TI - THE SOCIETY OF AMERICAN BACTERIOLOGISTS. PMID- 17740908 TI - A NEW THEORY REGARDING THE FEEDING POWER OF PLANTS. PMID- 17740910 TI - THE SOCIETY FOR PLANT MORPHOLOGY AND PHYSIOLOGY. PMID- 17740911 TI - THIRD ANNUAL MEETING OF THE CORDILLERAN SECTION OF THE GEOLOGICAL SOCIETY OF AMERICA. PMID- 17740912 TI - A NEW BAROMETRY FOR THE UNITED STATES, CANADA AND THE WEST INDIES. PMID- 17740913 TI - AGRICULTURE AND THE EXPERIMENT STATIONS. PMID- 17740914 TI - A GEOGRAPHICAL SOCIETY OF NORTH AMERICA. PMID- 17740916 TI - NOTES ON INORGANIC CHEMISTRY. PMID- 17740915 TI - INJURIES TO THE EYE, CAUSED BY INTENSE LIGHT. PMID- 17740918 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17740917 TI - THE PHYSIOLOGICAL EFFECTS OF THE ELECTRICAL CHARGE OF IONS. PMID- 17740919 TI - This Week in SCIENCE. PMID- 17740920 TI - Astrophysical plasmas. PMID- 17740922 TI - Science scope. PMID- 17740921 TI - Science, slogans, and civic duty. AB - We are beset with slogans for complex and controversial public issues that represent significant bodies of scientific knowledge. Public debate and action on these issues rarely adequately reflect such knowledge and seldom feature scientists playing central roles. Examples are assessment of educational effectiveness through assessment of student learning outcomes and the setting of scientific priorities across the full spectrum of scientific disciplines. It is an unfulfilled civic duty of scientists and engineers to engage themselves more fully and actively in public debate and action on important issues. PMID- 17740923 TI - Tiger teams draw researchers' snarls. PMID- 17740924 TI - "Buying into" the reforms. PMID- 17740925 TI - A lesson learned, again, at valdez. PMID- 17740927 TI - Fanning the hope for flat diamond. PMID- 17740926 TI - Acid rain program: mixed review. PMID- 17740928 TI - Mysterious celestial object found. PMID- 17740929 TI - Yucatan killer impact gaining support. PMID- 17740930 TI - Lynn Margulis: Science's Unruly Earth Mother. PMID- 17740931 TI - Gaia: myth or mechanism? PMID- 17740932 TI - Myths and maths. PMID- 17740933 TI - Looking for loyalty in DNA. PMID- 17740934 TI - CF Screening Studies Nearing Reality. PMID- 17740935 TI - Infectious disease grants. PMID- 17740936 TI - Dense astrophysical plasmas. AB - Degenerate bodies composed primarily of dense hydrogen and helium plasmas range from giant planets to the so far hypothetical brown dwarfs. More massive objects begin their lives as nondegenerate stars and may end as white dwarfs, composed primarily of carbon and oxygen, or as neutron stars, with solid crusts of iron or heavier elements and cores of neutron matter. The physical properties of dense plasmas that are necessary to construct theoretical models of such degenerate stars include the equation of state, transport properties, and nuclear reaction rates. PMID- 17740937 TI - Astrophysical jets. AB - Astrophysical jets are linear structures associated with stars and galaxies which span about seven orders of magnitude in size; the largest jets emanating from galaxies are about 100 times the size of our galaxy and are the largest single objects in the universe. Jets associated with stars are composed of ionized gas moving away from the star with velocities of a few hundred kilometers per second. Extragalactic jets are composed of relativistic particles, magnetic field, and probably additional amounts of cooler ionized plasma either originally ejected in the jet or entired by it out of the surrounding gaseous medium. The initial outflow velocity for extragalactic jets may be relativistic, and average outflow speeds of several thousand kilometers per second are likely. The energy flux carried by extragalactic jets may be in excess of 10(46) ergs per second, depending upon the nature of the jet. A definition of jet properties, deduced from their interaction with the ambient medium, can place essential constraints on models for the central power source in the parent galaxy or quasi-stellar object where they originate. PMID- 17740939 TI - The quasi-stationary and transient States of the solar wind. AB - There are two states of the solar wind: quasi-stationary and transient. After 30 years of measurements by interplanetary spacecraft, the differences in the physical properties of the two types of wind are fairly well determined, but the physical processes involved in their accelerations are not yet understood in detail. The solar wind exists in part because the upper solar atmosphere, called the corona, is very hot, but the heating mechanisms are also not well understood. Recent research suggests a link between the heating and acceleration mechanisms. PMID- 17740938 TI - Interstellar shock waves. AB - An understanding of interstellar shock waves is crucial in determining the structure of the interstellar medium. By causing the gas to radiate, interstellar shocks provide astronomers with valuable diagnostics on both the physical conditions in the interstellar medium and the energy source that produced the shock. The complexity of the interstellar plasma-its degree of ionization, its molecular content, the presence of small dust grains and cosmic rays, and the magnetic field-leads to a rich variety of structures for interstellar shocks, which are being actively investigated both observationally and theoretically. PMID- 17740940 TI - Plasma motions in planetary magnetospheres. AB - Before direct exploration by spacecraft, Jupiter was the only planet other than Earth that was known to have a magnetic field, as revealed by its nonthermal radio emissions. The term "magnetosphere" did not exist because there was no clear concept of such an entity. The space age provided the opportunity to explore Earth's neighborhood in space and to send instruments to seven of the other eight planets. It was found that interplanetary space is pervaded by a supersonic "solar wind" plasma and that six planets, including Earth, have magnetic fields of sufficient strength to deflect this solar wind and form a comet-shaped cavity called a magnetosphere. Comparative study of these magnetospheres aims to elucidate both the general principles and characteristics that they share in common, and the specific environmental factors that cause the important, and sometimes dramatic, differences in behavior between any two of them. A general understanding of planetary magnetospheres holds the promise of wide applicability in astrophysics, which, for the indefinite future, must rely solely on remote sensing for experimental data. PMID- 17740941 TI - Laser method for synthesis and processing of continuous diamond films on nondiamond substrates. AB - A laser method based upon carbon ion implantation and pulsed laser melting of copper has been used to produce continuous diamond thin film. Carbon ions were implanted with ion energies in the range of 60 to 120 keV, and doses of 1.0 x 10(18) to 2.0 x 10(18) ions cm(-2). The ion-implanted specimens were treated with nanosecond excimer laser pulses with the following parameters: energy density, 3.0 to 5.0 J cm(-2); wavelength, 0.308 microm; pulse width, 45 nanoseconds. The specimens were characterized with scanning electron microscopy (SEM), x-ray diffraction, Rutherford backscattering/ion channeling, Auger, and Raman spectroscopy. The macroscopic Raman spectra contained a strong peak at 1332 cm( 1) with full width at half maximum of 5 cm(-1), which is very close to the quality of the spectra obtained from single-crystal diamond. The selected area electron diffraction patterns and imaging confirmed the films to be defect-free single crystal over large areas of up to several square micrometers with no grain boundaries. Low voltage SEM imaging of surface features indicated the film to be continuous with presence of growth steps. PMID- 17740942 TI - Folding and unbinding transitions in tethered membranes. AB - Molecular dynamics simulations of tethered membranes indicate that an attraction between the monomers leads to a well-defined sequence of folding transitions with decreasing temperature. With insights gained from Landau theory and simulations of bimembranes, the folding transitions are found to be intimately linked to the unbinding of membranes. Finite-size effects, mainly due to the loss of entropy from edge fluctuations, play an important role in hindering folding transitions. PMID- 17740944 TI - Response. PMID- 17740945 TI - Regulation reexamined. PMID- 17740943 TI - The shapes and sizes of closed, pressurized random walks. AB - Two-dimensional cell-like membranes acted on by osmotic pressure differentials are represented by closed, unrestricted random walks. The treatment omits excluded-volume effects, and the pressure that is imposed thus favors an oriented area, so that the shriveled configuration of a vesicle with excess external pressure is inaccessible in this model. Nevertheless, the approach has the decided advantage of yielding analytic expressions in a complete statistical analysis. Results are presented for the average square of the radius of gyration, the asphericity, and the probability distribution of the principal components of the radius of gyration tensor. The analysis is done in both the constant-pressure and constant-area ensembles. PMID- 17740947 TI - Some other books of interest. PMID- 17740946 TI - AIDS from its begiings. PMID- 17740949 TI - Study of anomalous phenomena. PMID- 17740948 TI - Products & materials. PMID- 17740951 TI - Nuclear proliferation. PMID- 17740952 TI - Laser patents. PMID- 17740950 TI - Genetic screening. PMID- 17740953 TI - Laser patents. PMID- 17740954 TI - Origin of the theory of solutions. PMID- 17740955 TI - Differing values in academia and industry. PMID- 17740956 TI - Forecasting southern california earthquakes. AB - Since 1978 and 1979, California has had a significantly higher frequency of moderate to large earthquakes than in the preceding 25 years. In the past such periods have also been associated with major destructive earthquakes, of magnitude 7 or greater, and the annual probability of occurrence of such an event is now 13 percent in California. The increase in seismicity is associated with a marked deviation in the pattern of strain accumulation, a correlation that is physically plausible. Although great earthquakes (magnitude greater than 7.5) are too infrequent to have clear associations with any pattern of seismicity that is now observed, the San Andreas fault in southern California has accumulated sufficient potential displacement since the last rupture in 1857 to generate a great earthquake along part or all of its length. PMID- 17740957 TI - Repopulating the countryside: a 1980 census trend. AB - Census data confirm that in the 1970's population grew more rapidly outside than inside metropolitan territory, reversing a historic pattern. The new data reveal that the dispersion of population growth beyond metropolitan areas was not so much a movement to small towns as a movement to the open countryside. The trends appear strong enough to suggest a new shift toward rural life-styles. PMID- 17740958 TI - Air pollution clouds u.s.-Canadian relations. PMID- 17740960 TI - India-u.s. Deal falters. PMID- 17740959 TI - HUD's Orphan: Research on Lead Poisoning. PMID- 17740961 TI - Another setback for clinch river. PMID- 17740962 TI - Particle theorists in a quandary. PMID- 17740963 TI - Cultural evolution in mesoamerica. PMID- 17740964 TI - Island primates. PMID- 17740966 TI - Organelles. PMID- 17740965 TI - A botanical classification. PMID- 17740967 TI - Acceleration of uranium at the bevalac. AB - Recent upgrading projects have extended the mass range of particles that can be accelerated at the Bevalac to include any element of the periodic table to energies above 1 billion electron volts per atomic mass unit. This capability was verified on 11 May 1982 with the production of a uranium beam at 147.7 million electron volts per atomic mass unit. PMID- 17740968 TI - Characteristics of the ionization tracks and interactions of uranium-238 nuclei in emulsion. AB - The acceleration and extraction of uranium-238 nuclei by the Bevalac have been confirmed by their visual detection in nuclear research emulsion. A preliminary result for the collision mean free path for stopping uranium-238 (energy /= 5.8 +/- 0.4) in this region may have been restricted exclusively to South Carolina. Paleoliquefaction evidence for six large prehistoric earthquakes was discovered there. At least five of these past events originated in the Charleston, South Carolina, area, the locale of a magnitude 7+ event in 1886. During the past two millennia, large events may have occurred about every 500 to 600 years. PMID- 17741384 TI - The lesser known bohr. PMID- 17741383 TI - A water storage adaptation in the maya lowlands. AB - Prehispanic water management in the Maya Lowlands emphasized collection and storage rather than the canalization and diversion accentuated in highland Mexico. Reexamination of site maps of the ancient Maya city of Tikal, Guatemala, has revealed an important, overlooked factor in Maya centralization and urban settlement organization. In a geographical zone affected by an extended dry season and away from permanent water sources, large, well-planned reservoirs provided resource control as well as political leverage. PMID- 17741385 TI - Modes of leadership. PMID- 17741386 TI - The high-latitude oceans. PMID- 17741387 TI - Trophic topology. PMID- 17741388 TI - Products & materials. PMID- 17741389 TI - THE ORBITS OF FREELY FALLING BODIES. PMID- 17741390 TI - FUNCTIONS AND LIMITATIONS OF THE GOVERNING BOARD. PMID- 17741392 TI - BONAPARTE RESEARCH FUND GRANTS. PMID- 17741391 TI - INDIAN REMAINS IN MAINE. PMID- 17741393 TI - AGRICULTURAL EXTENSION. PMID- 17741394 TI - A NEW ATTACHMENT FOR THE HARVARD KYMOGRAPHION. PMID- 17741395 TI - ACCURACY IN STATING THE OCCURRENCE OF SPECIES. PMID- 17741396 TI - "QUITE A FEW". PMID- 17741398 TI - Letter to the editor. PMID- 17741397 TI - AN ILLUSTRATION OF THE INFLUENCE OF SUBSTRATUM HETEROGENEITY UPON EXPERIMENTAL RESULTS. PMID- 17741399 TI - Letter to the editor. PMID- 17741400 TI - Dyslexia. PMID- 17741401 TI - Kentucky health care. PMID- 17741402 TI - Letter to the editor. PMID- 17741403 TI - Calvert cliffs project. PMID- 17741404 TI - Santa cruz: a misunderstanding. PMID- 17741406 TI - Confused. PMID- 17741405 TI - Letter to the editor. PMID- 17741408 TI - Manpower in science and engineering, based on a saturation model. PMID- 17741407 TI - Mariner ultraviolet spectrometer: topography and polar cap. AB - Mars, the red planet, reflects sunlight in the ultraviolet, but it is the atmosphere, not the surface, that is responsible for the reflected light. Even though there are atmospheric scatterers in addition to the molecular scatterers, it is possible to relate the intensity of the scattered radiation with the atmospheric pressure. The variation of pressure over the planet reveals the topography to vary over 7 kilometers in height and to be correlated with visible features. The carbon dioxide polar cap, in addition to being a cold trap for volatile gases in the atmosphere, may alsobe a very efficient adsorption trap for nonvolatiles. This last property may make the cap a repository for gases produced by geological or biological activity (15). PMID- 17741409 TI - Sex discrimination on campus: michigan wrestles with equal pay. PMID- 17741410 TI - Congress considers equal pay rights for academic women. PMID- 17741411 TI - NOAA and Oceanographic Research "Wet NASA" Idea Dries Up. PMID- 17741412 TI - NSF to the Rescue. PMID- 17741413 TI - Campaign conquers senate. PMID- 17741414 TI - Program given notice. PMID- 17741415 TI - Lead poisoning: zoo animals may be the first victims. AB - In the article "Lead Poisoning: Zoo animals may be the first victims" (p. 130, 9 July), an erroneous figure was given in column 3, paragraph 3, lines 5 and 6. It should have read 3900 micrograms per gram of dry weight. PMID- 17741416 TI - Quasars revisited: rapid time variations observed via very-long-baseline interferometry. AB - Recent Goldstone-Haystack radio interferometric observations of the quasars 3C 279 and 3C 273 reveal rapid variations in their fine structure. Most notably, the data for 3C 279, interpreted in terms of a symmetric double-source model and the accepted red-shift distance, indicate differential proper motion corresponding to an apparent speed about ten times that of light. A number of possible mechanisms that might give rise to such an apparent speed are considered; although several may be plausible, no definitive choice can be made on the basis of present evidence. More interferometric observations of quasars are clearly needed to clarify their structure and internal kinematics. PMID- 17741417 TI - Underground nuclear explosions: tectonic utility and dangers. AB - The tectonic strain energy released by several underground nuclear explosions has been calculated through an analysis of seismic surface waves. The proportionally great amount of energy released in certain events suggests the possible uses for, as well as the hazards of, underground testing. PMID- 17741419 TI - Synthetic calcareous pseudomorphs formed from siliceous microstructures. AB - Individuals of the diatom Coscinodiscus have been treated hydrothermally in the presence of lime and carbon dioxide with the result that they have been pseudomorphed by calcite. The silica of the original diatoms has been replaced while the intricate reticulations of the alveoli have been preserved down to submicroscopic detail. PMID- 17741418 TI - Fossil fuel combustion and the major sedimentary cycle. AB - The combustion of the fossil fuels coal, oil, and lignite potentially can mobilize many elements into the atmosphere at rates, in general, less than but comparable to their rates of flow through natural waters during the weathering cycle. Since the principal sites of fossil fuel combustion are in the mid latitudes of the Northern Hemisphere, changes in the composition of natural waters and air, as a consequence of this activity, will be most evident at these latitudes. PMID- 17741420 TI - Aromatic hydrocarbons in the murchison meteorite. AB - Polynuclear aromatic hydrocarbons in the Murchison meteorite have been identified by the combined techniques of gas chromatography and mass spectrometry. The distribution of the aromatic compounds suggests that they are the products of a high-temperature synthesis. PMID- 17741422 TI - Trout leukocytes: growth in oxygenated cultures. AB - A reproducible method of culturing leukocytes from rainbow trout (Salmo gairdneri) has been found. Using an atmosphere of 100 percent oxygen, we stimulated peripheral blood leukocytes to divide at 19 degrees C. Cultured cells were used for a karyological study; they had a modal chromosome number of 60 and a constant arm number of 104, a value previously reported for other tissues in these fish. PMID- 17741421 TI - Blowflies: Alteration of Adult Taste Responses by Chemicals Present during Development. AB - The addition of certain sugars to the food consumed during larval development increases the taste sensitivity of adult blowflies to some sugars, decreases it to others, and is without effect on the sensitivity to still others. No correlation with metabolic phenomena is apparent. The hypothesis that repression of inductible enzyme synthesis by glucose is a relevant model is not supported. PMID- 17741423 TI - Plant Response to Carbon Dioxide Enrichment under Field Conditions: A Simulation. AB - A comprehensive soil-plant-atmosphere computer simulation model (SPAM) predicted up to a 45 percent increase in carbon dioxide uptake by a crop enriched with carbon dioxide at ground level. Enrichment rates of 225 and 450 kilograms of carbon dioxide per hectare per hour were used. Simulations covered a wide range of wind speed, crop height, and leaf area display. PMID- 17741424 TI - Habituation of electrically induced readiness to gnaw. AB - Electrical stimulation of the hypothalamus in prairie dogs (Cynomys ludovicianus) produced a readiness to gnaw which decreased over time, exhibited spontaneous recovery, and could be dishabituated by foot shock. The response decrement was in part habituatory and could modify the interaction between a stimulation-induced readiness to gnaw and a physiologically induced hunger. Functional plasticity of stimulation-induced behavior might be accounted for, in part, by habituation. PMID- 17741426 TI - COAST SURVEY PARTIES IN ALASKA. PMID- 17741425 TI - THE LATEST RESULTS OF ORIENTAL ARCHAeOLOGY. PMID- 17741428 TI - VASSAR STUDENTS' AID SOCIETY. PMID- 17741427 TI - THE PRESERVATION OF TIMBER. PMID- 17741429 TI - THE FORESTS OF ANNAM. PMID- 17741430 TI - GEM-MINING IN SIAM. PMID- 17741431 TI - HEALTH MATTERS. PMID- 17741433 TI - The Micro-Organisms of Standing Water. PMID- 17741432 TI - THE BOTANICAL MYTHOLOGY OF THE HINDOOS. PMID- 17741435 TI - The Curaility of Galloping Consumption. PMID- 17741434 TI - Cancer Mortality among the Jews. PMID- 17741437 TI - Right-Handedness. PMID- 17741438 TI - Osteological Notes. PMID- 17741436 TI - The Protection from Diphtheria and Tetanus by Inoculation. PMID- 17741439 TI - Onoadaga Folk-Lore. PMID- 17741441 TI - This week in science. PMID- 17741440 TI - INDUSTRIAL NOTES. PMID- 17741442 TI - The 3 k microwave background and olbers' paradox. PMID- 17741443 TI - College calculus: how should it be taught? PMID- 17741444 TI - College calculus: how should it be taught? PMID- 17741446 TI - NAS Elects New Members. PMID- 17741445 TI - Fresh look at Acid rain. PMID- 17741447 TI - Mathematics at 100. PMID- 17741448 TI - A New Tool Maker the Hominid Record?: New data from Australopithecine hand bones challenge the long-held assumption that only members of the genus Homo are capable of making and using tools. PMID- 17741449 TI - One species ... One tool. PMID- 17741450 TI - Supernova 1987A! AB - Light from the brightest supernova in almost 400 years arrived at Earth on 23 February 1987. Although located 160,000 light years away in a satellite galaxy of our own known as the Large Magellanic Cloud, this supernova's relative proximity compared to all others that have been observed in modern times has allowed observations, which were never possible before, to be made from space, from detectors on the ground and carried by balloons and airplanes, and from neutrino detectors deep underground. What emerges is a greater understanding of one of the most violent events in the universe, the death of a massive star. For the most part, theoretical expectations have been borne out, but some major surprises have made the event all the more fascinating. PMID- 17741451 TI - The nature of the interior of uranus based on studies of planetary ices at high dynamic pressure. AB - Data from the Voyager II spacecraft showed that Uranus has a large magnetic field with geometry similar to an offset tilted dipole. To interpret the origin of the magnetic field, measurements were made of electrical conductivity and equation-of state data of the planetary "ices" ammonia, methane, and "synthetic Uranus" at shock pressures and temperatures up to 75 gigapascals and 5000 K. These pressures and temperatures correspond to conditions at the depths at which the surface magnetic field is generated. Above 40 gigapascals the conductivities of synthetic Uranus, water, and ammonia plateau at about 20(ohm-cm)(-1), providing an upper limit for the electrical conductivity used in kinematic or dynamo calculations. The nature of materials at the extreme conditions in the interior is discussed. PMID- 17741452 TI - Middle mississippian blastoid extinction event. AB - The Middle Mississippian blastoid (Phylum Echinodermata) extinction event (about 340 million years ago) was a rapid, habitat-specific extinction. Blastoids became rare or absent in shallow-water environments after the extinction, and this change was probably synchronous worldwide. Onshore-offshore habitat shifts have been recognized as an important historical trend among marine benthos. Unlike trends exhibited by other groups, blastoids appear to have repopulated shallow water habitats after a period of diminished diversity and abundance. PMID- 17741453 TI - New zealand marine terraces: uplift rates. PMID- 17741454 TI - Response:new zealand marine terraces: uplift rates. PMID- 17741455 TI - Forum to focus on science teaching. PMID- 17741456 TI - AAAS-African Programs Under Way. PMID- 17741457 TI - Regional seminar focuses on Caribbean science and technology. PMID- 17741458 TI - Reminder for members. PMID- 17741459 TI - Pacific division meets in corvallis, 18 to 22 june. PMID- 17741460 TI - Obituaries. PMID- 17741461 TI - Health care assessment: hospital structure and performance. PMID- 17741462 TI - Ceramics in archeology: pottery analysis. PMID- 17741463 TI - Terrains under water: geology and geochemistry of abyssal plains. PMID- 17741464 TI - African rifts: sedimentation in the african rifts. PMID- 17741465 TI - PC Software for Artificial Intelligence Applications. AB - Our review has emphasized that AI tools are programming languages inspired by some problem-solving paradigm. We want to underscore their status as programming languages; even if an AI tool seems to fit a problem perfectly, its proficient use still requires the training and practice associated with any programming language. The programming manuals for PC-Plus, Smalltalk/ V, and Nexpert Object are all tutorial in nature, and the corresponding software packages come with sample applications. We find the manuals to be uniformly good introductions that try to anticipate the problems of a user who is new to the technology. All three vendors offer free technical support by telephone to licensed users. AI tools are sometimes oversold as a way to make programming easy or to avoid it altogether. The truth is that AI tools demand programming-but programming that allows you to concentrate on the essentials of the problem. If we had to implement a diagnostic system, we would look first to a product such as PC-Plus rather than BASIC or C, because PC-Plus is designed specifically for such a problem, whereas these conventional languages are not. If we had to implement a system that required graphical interfaces and could benefit from inheritance, we would look first to an object-oriented system such as Smalltalk/V that provides built-in mechanisms for both. If we had to implement an expert system that called for some mix of AI and conventional techniques, we would look first to a product such as Nexpert Object that integrates various problem-solving technologies. Finally, we might use FORTRAN if we were concerned primarily with programming a well-defined numerical algorithm. AI tools are a valuable complement to traditional languages. PMID- 17741466 TI - Products & materials. PMID- 17741467 TI - THE TEACHING OF PHYSIOLOGY. PMID- 17741468 TI - THE MODE OF ACTION OF SULPHANILAMID. PMID- 17741469 TI - DIURNAL CYCLE OF HEAT RESISTANCE IN PLANTS. PMID- 17741471 TI - NIEVES PENITENTES NEAR BOSTON, MASSACHUSETTS. PMID- 17741470 TI - PACIFIC ENTOMOLOGICAL SURVEY. PMID- 17741472 TI - LANGUAGE DIFFICULTY. PMID- 17741474 TI - GRANTS FOR RESEARCH OF THE GEOLOGICAL SOCIETY OF AMERICA. PMID- 17741473 TI - SPECIAL RESEARCH CONFERENCES ON CHEMISTRY. PMID- 17741476 TI - LIVER EXTRACT AS A SUBSTITUTE FOR SERUM IN THE CULTURE MEDIUM FOR ENDAMOEBA HISTOLYTICA. PMID- 17741475 TI - ON THE PRESENCE OF AZOTOBACTER AGILIS IN AMERICA. PMID- 17741477 TI - ADRENAL ATROPHY AND SENESCENCE PRODUCED BY A VITAMIN DEFICIENCY. PMID- 17741478 TI - BACTERIAL LEAF-SPOT DISEASES. PMID- 17741479 TI - A SYSTEM OF INDEXING 2x2 INCH SLIDES. PMID- 17741480 TI - LANTERN SLIDES FROM TYPEWRITTEN MATERIAL. PMID- 17741481 TI - ADDRESS AT THE DEDICATION OF THE WALKER LABORATORY OF THE RENSSELAER POLYTECHNIC INSTITUTE. PMID- 17741482 TI - THE RATIONAL BASIS OF MATHEMATICAL PEDAGOGY. PMID- 17741484 TI - THE ARTIFICIAL PRODUCTION OF MUTANTS. PMID- 17741483 TI - THE PARASITISM OF NEOCOSMOSPORA--INFERENCE VERSUS FACT. PMID- 17741486 TI - PATAGONIA AND ANTARCTICA. PMID- 17741485 TI - ENGLISH AS SHE IS WRITTEN. PMID- 17741487 TI - CURRENT NOTES ON LAND FORMS. PMID- 17741488 TI - INTERNATIONAL CONFERENCE ON PLANT HARDINESS AND ACCLIMATIZATION. PMID- 17741489 TI - THE BRITISH MUSEUM. PMID- 17741490 TI - THE RELATION OF MODERN CHEMISTRY TO MODERN MEDICINE. PMID- 17741491 TI - APPENDICITIS AND THE RACE. PMID- 17741492 TI - 'THE TREE-DWELLERS.'. PMID- 17741493 TI - MONT PELE FROM OCTOBER 20, 1903, TO MAY 20, 1904. PMID- 17741494 TI - THE PTERIDOSPERMAPHYTA. PMID- 17741495 TI - THE OCCURRENCE OF TAURIN IN INVERTEBRATE MUSCLE. PMID- 17741497 TI - LABORATORIES FOR BOTANICAL RESEARCH. PMID- 17741496 TI - INFLUENCE OF BORIC ACID AND BORAX ON DIGESTION AND HEALTH. PMID- 17741498 TI - INTERNATIONAL CATALOGUE OF SCIENTIFIC LITERATURE. PMID- 17741499 TI - THE APPROPRIATIONS FOR THE DEPARTMENT OF AGRICULTURE FOR 1901. PMID- 17741500 TI - VARIATION AND SOME PHENOMENA CONNECTED WITH REPRODUCTION AND SEX. PMID- 17741501 TI - THE PROTEIDS OF LIVING MATTER. PMID- 17741502 TI - THE NEW YORK BOTANICAL GARDEN. PMID- 17741504 TI - Laboratory Exercises with Outlines for the Study of (Chemistry, to accompany any Elementary Text. PMID- 17741503 TI - School Chemistry. PMID- 17741505 TI - THE STUDY OF GREEK AND LATIN VS. MODERN LANGUAGES. PMID- 17741506 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17741508 TI - CURRENT NOTES ON PHYSIOGRAPHY. PMID- 17741507 TI - PHOSPHORESCENCE IN DEEP-SEA ANIMALS. PMID- 17741509 TI - SCIENCE NEWS. PMID- 17741511 TI - AN ALGONKIAN JELLYFISH FROM THE GRAND CANYON OF THE COLORADO. PMID- 17741510 TI - VISION IN NATURE AND VISION AIDED BY SCIENCE; SCIENCE AND WARFARE. PMID- 17741513 TI - A NEW LOCALITY FOR THE VENUS' FLY-TRAP (DIONAEA MUSCIPULA). PMID- 17741512 TI - A RAINBOW AT NIGHT. PMID- 17741514 TI - ISOLATION OF A FILTRABLE, TRANSMISSIBLE AGENT WITH "NEUROLYTI" PROPERTIES FROM TOXOPLASMA-INFECTED TISSUES. PMID- 17741515 TI - INTERCELLULAR WOUND HORMONES PRODUCED BY HETEROAUXIN. PMID- 17741516 TI - CHANGES IN WHEAT METABOLISM CAUSED BY POWDERY MILDEW. PMID- 17741517 TI - A PRACTICAL BELLOWS RECORDER. PMID- 17741519 TI - Letters to the Editor. PMID- 17741518 TI - "PROPS" FOR COVER GLASSES. PMID- 17741520 TI - Biology and Metaphysics. PMID- 17741522 TI - Letters to the Editor. PMID- 17741521 TI - Letters to the Editor. PMID- 17741523 TI - The Use of "I". PMID- 17741524 TI - Educational Tests. PMID- 17741525 TI - Organic Photochemistry. PMID- 17741526 TI - Population Planning: 1963 Marked by Reduction of Controversy and Shift in Government Attitude. PMID- 17741528 TI - COMSAT: Private Satellite Firm Working Out Ties with Government; Basic Decisions Are Still Open. PMID- 17741527 TI - Education Legislation: Deadlock on Vocational Education Broken; Landmark College Aid Bill Passed. PMID- 17741529 TI - Temperature of an Iron Meteoroid in Space. AB - The solar absorptance and hemispherical emittance of meteoritic iron has been measured from -100 degrees to 300 degrees C for a surface characterized by a 400 grit finish. If it is assumed that 10 percent of the surface is optically black because of holes and cracks, the temperature of an iron meteoroid at the earth's mean distance from the sun would be about 90 degrees C. PMID- 17741530 TI - Tellurium Content of Marine Manganese Oxides and Other Manganese Oxides. AB - Tellurium in amounts ranging from 5 to 125 parts per million was present in all of 12 samples of manganese oxide nodules from the floor of the Pacific and Indian oceans. These samples represent the first recognized points of high tellurium concentration in a sedimentary cycle. The analyses may lend support to the theory that the minor-element content of sea-floor manganese nodules is derived from volcanic emanations. PMID- 17741531 TI - Species Abundance: Natural Regulation of Insular Variation. AB - Variation in numbers of land plant species on islands in the Galapagos Archipelago can be predicted on the basis of elevation, area of the adjacent island, distance from the nearest island, and distance from the center of the archipelago, but not on the basis of the area of the host island. Multiple linear regression (y = bx(1) + bx(2) . . .) gives better "goodness of fit" than curvilinear analysis (y = bx(z)). The variation in number of species on large islands can be predicted more accurately than the variation on small ones. Ecologic diversity and isolation are the natural regulators of species abundance. PMID- 17741532 TI - Radiation Hazard in Space from Solar Particles. AB - There were about six solar flare events during the last solar cycle which would have exposed a space traveler to serious radiation from solar particles. The radiation from two of these events was intense enough to necessitate extra precautions being taken to protect space travelers. PMID- 17741533 TI - Abscisin II, an Abscission-Accelerating Substance from Young Cotton Fruit. AB - Crystalline abscisin II, with a tentative molecular formula of C(15)H(20)O(4), has been isolated from young cotton fruit. It accelerates abscission when applied in amounts as low as 0.01 microg per abscission zone. It inhibits indoleacetic acid-induced straight growth of Avena coleoptiles but has no gibberellin activity on dwarf maize. PMID- 17741534 TI - Geodesy and Geophysics. PMID- 17741536 TI - Forthcoming Events. PMID- 17741535 TI - Yeast Genetics Conference. PMID- 17741537 TI - THEOBALD SMITH. PMID- 17741539 TI - NORMAL "VISUAL HEARING". PMID- 17741538 TI - THE TRAINING OF TEACHERS OF MATHEMATICS. PMID- 17741540 TI - THE DESTRUCTION OF "VERMIN". PMID- 17741541 TI - A PHENOMENON IN FUNGI IMPERFECTI. PMID- 17741542 TI - RESEARCH PROGRAM OF THE ILLINOIS STATE GEOLOGICAL SURVEY. PMID- 17741543 TI - NATURE OF CRYSTALS FOUND IN AMOEBA. PMID- 17741544 TI - THE CULTIVATION OF THE VIRUS OF ST. LOUIS ENCEPHALITIS. PMID- 17741546 TI - A GENERAL SOURCE OF RADIATION FOR THE VISIBLE AND INFRARED SPECTRUM. PMID- 17741545 TI - PLANT PIGMENTS AND REPRODUCTION. PMID- 17741547 TI - LOCALIZED VITAL STAINING OF TELEOSTEAN EMBRYOS. PMID- 17741549 TI - The American Philosophical Society: Abstracts of Papers Presented at Autumn General Meeting. PMID- 17741548 TI - The Chemical Components of Onion Vapors Responsible for Wound-healing Qualities. PMID- 17741550 TI - Ellsworth Huntington, 1876-1947. PMID- 17741551 TI - The Common Cold: A Note Regarding Isolation of an Agent. PMID- 17741552 TI - The Effects of Vitamins on Phosphorus Metabolism in the Chick Embryo: 1. Vitamin D and the Utilization of Inorganic Phosphorus. PMID- 17741553 TI - Streptomycin Therapy in Experimental Tuberculosis of Guinea Pigs Infected Intracerebrally With Virulent Tubercle Bacilli. PMID- 17741554 TI - "Acid Phosphatase" Reactions in Peripheral Nerves. PMID- 17741555 TI - Polydactyly and Limb Duplication Occurring Naturally in the Tiger Salamander, Ambystoma tigrinum. PMID- 17741556 TI - Antibiotic Activity of Subtilin and Streptomycin in the Presence of BAL. PMID- 17741557 TI - Effect of Flavonols on Clostridium botulinum. PMID- 17741559 TI - A Flower Marker for Plant-breeding Operations. PMID- 17741558 TI - Inadequate Maternal Nutrition and Hydrocephalus in Infant Rats. PMID- 17741560 TI - Polytetrafluoroethylene for the Prevention of Bumping From Superheating of Boiling Fluids. PMID- 17741562 TI - THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE THE CONTROVERSY BETWEEN MATERIALISM AND VITALISM: CAN IT BE ENDED? PMID- 17741561 TI - Mounting of Dermatological Material With Synthetic Resins. PMID- 17741564 TI - CHARLES HUGH SHAW. PMID- 17741563 TI - INVESTIGATIONS OF THE CARNEGIE INSTITUTION. PMID- 17741565 TI - THE UNIVERSITY OF ILLINOIS MOVEMENT FOR A UNIVERSITY CONSTITUTION. PMID- 17741566 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17741567 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17741568 TI - LARVAL SPECIES. PMID- 17741569 TI - THE GERM-CELL DETERMINANTS OF CHRYSOMELID EGGS. PMID- 17741570 TI - THE PYTHAGOREAN THEOREM. PMID- 17741571 TI - THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE SECTION E. PMID- 17741573 TI - SCIENCE IN CANADA. PMID- 17741572 TI - A DYNAMICAL HYPOTHESIS OF INHERITANCE (II.). PMID- 17741574 TI - CARL LUDWIG. PMID- 17741575 TI - THE FROG WAS NOT BRAINLESS BUT DECEREBRIZED. PMID- 17741576 TI - COMMENT AND CRITICISM. PMID- 17741577 TI - LETTERS TO THE EDITOR. PMID- 17741579 TI - Inertia. PMID- 17741580 TI - LETTERS TO THE EDITOR. PMID- 17741578 TI - LETTERS TO THE EDITOR. PMID- 17741581 TI - LETTERS TO THE EDITOR. PMID- 17741582 TI - LETTERS TO THE EDITOR. PMID- 17741583 TI - Dalmanites in the lower carboniferous rocks. PMID- 17741584 TI - Thermometer exposure. PMID- 17741585 TI - Silk-culture in the colonies. PMID- 17741586 TI - A half-starved pig. PMID- 17741587 TI - 'A curious optical phenomenon.'. PMID- 17741589 TI - WINTERING IN THE ARCTIC. PMID- 17741588 TI - THE SCIENTIFIC METHOD IN HISTORICAL STUDY. PMID- 17741590 TI - BESTOWAL OF THE GRAND HONORARY WALKER PRIZE ON PROFESSOR JAMES HALL. PMID- 17741592 TI - THE CHOLERA BACILLUS. PMID- 17741591 TI - THE CANTILEVER-BRIDGE AT NIAGARA FALLS. PMID- 17741593 TI - THE EXPLORING VOYAGE OF THE CHALLENGER. PMID- 17741594 TI - RAIN IN BELGIUM. PMID- 17741595 TI - A NEW ASTRONOMICAL JOURNAL. PMID- 17741596 TI - INTELLIGENCE FROM AMERICAN SCIENTIFIC STATIONS. PMID- 17741597 TI - THE SMITHSONIAN INSTITUTION. PMID- 17741599 TI - ON THE CLASSIFICATION OF MUSEUMS. PMID- 17741598 TI - MEMORIAL TRIBUTE TO PROFESSOR THOMAS H. HUXLEY. PMID- 17741600 TI - THE X-RAYS. PMID- 17741601 TI - ASTRONOMY. PMID- 17741602 TI - THE METRIC SYSTEM. PMID- 17741603 TI - IMPROVED BLACKBOARD. PMID- 17741604 TI - The Department of Astronomy of the University of Chicago. PMID- 17741605 TI - Some Reminiscences of the Yerkes Observatory, 1898-1904. PMID- 17741606 TI - Studies of the Stellar System. PMID- 17741607 TI - Astrometry. PMID- 17741608 TI - Stellar Spectroscopy. PMID- 17741610 TI - The Spectroscopic Laboratory. PMID- 17741609 TI - Solar Research and Theoretical Astrophysics. PMID- 17741611 TI - The Yerkes Observatory: Past, Present, and Future. PMID- 17741613 TI - Scienttfic Book Register. PMID- 17741612 TI - COMMENTS by Readers. PMID- 17741614 TI - Ground-Based Astronomy: The NAS 10-Year Program. PMID- 17741616 TI - Conservation of what? PMID- 17741615 TI - Letters to the editor. PMID- 17741617 TI - Letters to the editor. PMID- 17741618 TI - Letters to the editor. PMID- 17741619 TI - Letters to the editor. PMID- 17741620 TI - Linear Algebra: Teacher's Problem. PMID- 17741621 TI - Letters to the editor. PMID- 17741622 TI - Peaceful Uses of the Earth's Atmosphere. PMID- 17741623 TI - Solar and interplanetary magnetic fields. PMID- 17741624 TI - Speciation in flowering plants. PMID- 17741625 TI - Computers and copyrights. PMID- 17741627 TI - Congress: private universities say unemployment pay should not cover their faculty, students. PMID- 17741626 TI - Science Policy: When Congress Looks for a Leader NSF Is Usually Nominated. PMID- 17741628 TI - Vietnam: jungle conflict poses new R & d problems. PMID- 17741629 TI - Transatlantic cooperation on research: new u.s. Moves. PMID- 17741631 TI - Oxygen isotope fractionation in the system dolomite-calcite-carbon dioxide. AB - Oxygen isotopes were equilibrated between carbon dioxide and calcite at four temperatures in the range 350 degrees to 610 degrees C and between carbon dioxide and dolomite at 350 degrees and 400 degrees C. Carbon of unusual isotopic composition was used as a tracer to demonstrate the nature and extent of the exchange process. Extrapolation of these data at lower temperatures indicates that at 25 degrees C dolomite is enriched in oxygen-18 by 6.8 per mil with respect to calcite. This result indicates that those natural dolomite-calcite assemblages which show very small fractionations were not formed in isotopic equilibrium. PMID- 17741630 TI - Weakening of dunite by serpentine dehydration. AB - A shear press has been used to determine the mechanical behavior of serpentinized dunite and forsterite at normal pressures to 50 kilobars, temperatures to 900 degrees C; and strain rates from 10(-1) to 10(-4) per second. The shear strength of dunite, containing less than 5 percent by volume of serpentine, is reduced by at least 30 percent as the temperature is raised from 300 degrees to 520 degrees C. Abundant kink bands develop at normal pressures above 35 kilobars at 27 degrees C and at lower pressures as the temperature is increased. PMID- 17741632 TI - Rotation of the planet mercury. AB - The equations of motion for the rotation of Mercury are solved for the general case by an asymptotic expansion. The findings of Liu and O'Keefe, obtained by numerical integration of a special case, that it is possible for Mercury's rotation to be locked into a 2:3 resonance with its revolution, are confirmed in detail. The general solution has further applications. PMID- 17741633 TI - Chromium-51 in sea water: chemistry. AB - Chromium-SI introduced into the Pacific Ocean from the Columbia River remains in the hexavalent state. Analysis of this radionuclide in sea water by hydroxide coprecipitation with iron is best accomplished if the chromium-51 is first reduced to the trivalent state. PMID- 17741634 TI - Pigment protein complex from gonyaulax. AB - A water-soluble peridinin-chlorophyll-protein complex from the dinoflagellate Gonyaulax polyedra was found to have a molecular weight of about 38,000. The complex could be disrupted by digestion with proteolytic enzymes. No electron transfer was observed when the complex was irradiated. PMID- 17741636 TI - Scolytid beetles associated with douglas fir: response to terpenes. AB - Douglas-fir oleoresin and the terpene hydrocarbons (alpha-pinene, beta-pinene, litnonene, camphene, geraniol, and alpha-terpineol) attracted various bark and timber beetles associated with Douiglas-fir forests during their flight. In responding to these volatile terpenes the bettles are directed to favorable breeding material. PMID- 17741635 TI - Naphthaleneacetic Acid: localization in the abscission zone of the bean. AB - When (14)C-naphthaleneacetic acid, labeled in the ring, was applied to the petiolar stuib of debladed bean (Phaseolus vulgaris L.) plants, it accumulated in or between cell walls of tissue immediately adjacent and distal to the abscission layer. There was no localization in the abscission layer per se. Similar distribution patterns were observed in the abscission zone after naphthaleneacetic acid applications, which either delayed (10(-3)M) or accelerated (10(-5)M) abscission. PMID- 17741638 TI - New light on how certain amines act in the brain. PMID- 17741637 TI - Composition of Combustible Concretions of the Alewife, Alosa pseudoharengus. AB - Alewives, Alosa pseudoharengus, wash ashore from Onondaga Lake, N.Y., in the form of combustible concretions in which the mnuscles are replaced by calcium salts of fatty acids. In both distribution pattern and total concentration of fatty acids the concretions differ strikingly from normal carcasses. Carbon-13: carbon-12 ratios indicate that the concretions may have formed from lipids of terrestrial or freshwater organisms or from organic pollutants of nonmarine origin, or from lipids and pollutants. PMID- 17741639 TI - Forthcoming events. PMID- 17741640 TI - Control of ph.d. Programs. PMID- 17741641 TI - Myeloma and atomic veterans. PMID- 17741642 TI - Improving r&d productivity: the federal role. AB - Despite widespread concern about lagging productivity growth rates and renewed interest in research, federal support for the review and packaging of hard-won new knowledge continues to languish. Yet accurate, accessible data are critical, not only in every R&D project but also in the most advanced manufacturing processes. Ensuring reliable, retrievable data is not a function that can be left to the professional societies, the publishing industry, or the private sector. In this article a six-point national science and technology data policy is proposed, and it is suggested that progress ultimately will depend on an overall science and technology policy, the first priority of which is to make available existing knowledge. PMID- 17741643 TI - Antisatellite Weapon Sets Dangerous Course: The United States is about to test an ASAT that has no obvious target except Soviet early-warning satellites. PMID- 17741644 TI - Carving Up TMI's Class Action Fund: The law firm that sued the utility is now being criticized by local groups for its management of a $5-million research fund. PMID- 17741646 TI - Hinckley starting mental illness fund. PMID- 17741645 TI - Firms Battle over Anticancer Drug. PMID- 17741647 TI - USDA Relents on Landsat. PMID- 17741648 TI - Stanford says yes to modified weapons proposal. PMID- 17741649 TI - Brotherly Alliances Help Avoid Inbreeding: Patterns of inbreeding avoidance behavior in vervet monkeys has a profound influence on the social organization of neighboring groups. PMID- 17741651 TI - Fuels from Solar Energy: How Soon?: Texas Instruments has the jump on a commercial photoelectrochemical system, but other systems under study could eventually be cheaper. PMID- 17741650 TI - New phylum discovered, named. PMID- 17741652 TI - AAAS Annual Meeting New York 24-29 May 1984: Poster Sessions Only--Deadline 20 January 1984. PMID- 17741653 TI - Bird song: acoustic communication in birds. PMID- 17741654 TI - Evolutionary theories: the eclipse of darwinism. PMID- 17741655 TI - Neuromorphology: the central nervous system of cartilaginous fishes. PMID- 17741656 TI - Distributional patterns: biogeography. PMID- 17741658 TI - Solar system ice: amorphous or crystalline? AB - The role of meteoritic bombardment on icy surfaces in the solar system is investigated. Using recent theoretical results concerning the nature of ejecta from impact craters in ice, the author concludes that the ratio of amorphous to crystalline ice surfaces should be lower then 1.0. PMID- 17741657 TI - Rates of evolution: effects of time and temporal scaling. AB - Rates of morphological evolution documented in laboratory selection experiments, historical colonization events, and the fossil record are inversely related to the interval of time over which they are measured. This inverse relationship is an artifact of comparing a narrow range of morphological variation over a wide range of time intervals, and it is also a product of time averaging. Rates measured over different intervals of time must be scaled against interval length before they can be compared. PMID- 17741659 TI - New burgess shale fossil sites reveal middle cambrian faunal complex. AB - Soft-bodied and lightly sclerotized Burgess shale fossils have been found at more than a dozen new localities in an area extending for 20 kilometers along the front of the Cathedral Escarpment in the Middle Cambrian Stephen Formation of the Canadian Rockies. Five different fossil assemblages from four stratigraphic levels have been recognized. These assemblages represent distinct penecontemporaneous marine communities that together make up a normal fore-reef faunal complex. PMID- 17741660 TI - SCIENCE NEWS. PMID- 17741661 TI - SIGNIFICANCE OF THE ETHER-DRIFT EXPERIMENTS OF 1925 AT MOUNT WILSON. PMID- 17741662 TI - EXISTING PRACTICES OF POLLUTING PUBLIC WATER COURSES. PMID- 17741663 TI - AWARDS OF THE JOHN SIMON GUGGENHEIM MEMORIAL FELLOWSHIPS. PMID- 17741665 TI - THE HABITS OF THE GRUNION. PMID- 17741664 TI - ADSORPTION MECHANISMS. PMID- 17741666 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17741667 TI - WHO DISCOVERED VITAMINES? PMID- 17741668 TI - CITATIONS OF SCIENTIFIC LITERATURE. PMID- 17741670 TI - A SIMPLE METHOD FOR OBSERVATION OF THE LIVING CHICK EMBRYO. PMID- 17741669 TI - RAILROAD PASSES FOR SCIENTIFIC WORK. PMID- 17741671 TI - THE ORIGIN OF VACUOLES. PMID- 17741672 TI - THE TRANSFER OF EXCITED ENERGY FROM OZONE TO HYDROGEN AND NITROGEN. PMID- 17741673 TI - THE POSITION OF THE CHEMIST IN THE COMMONWEALTH. PMID- 17741674 TI - INTERNATIONAL CONGRESSES. PMID- 17741676 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17741675 TI - WILLIAM JAMES. PMID- 17741677 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17741678 TI - THE LOCUS OF A MOVING POINT WHEN THE QUOTIENT OF ITS DISTANCES FROM TWO FIXED POINTS IS CONSTANT. PMID- 17741679 TI - THE DOCTOR AND THE PUBLIC. PMID- 17741680 TI - BOTANICAL NOTES. PMID- 17741681 TI - A FURTHER STATISTICAL STUDY OF AMERICAN MEN OF SCIENCE. PMID- 17741682 TI - Outer continental shelf operating regulations. PMID- 17741683 TI - Chrysotile asbestos: effects of human exposure. PMID- 17741684 TI - Conservation: the Minnesota plan. PMID- 17741685 TI - Oxygen and hydrogen isotopic ratios in plant cellulose. AB - The variations of the D/H and (18)O/(16)O ratios of nonexchangeable hydrogen and oxygen in plant cellulose reveal systematic differences between terrestrial plant groups. The slope of deltaD versus delta(18)O of cellulose from a variety of aquatic plants is close to 8 (the meteoric water value), while the slope for a number of terrestrial species is greater than or equal to about 24. Two models involving incorporation of CO(2) and H(2)O into cellulose precursors are proposed to account for these differences. Effects of evaporative transpiration on the isotopic composition of water in leaves are measured and discussed in the context of these models. PMID- 17741686 TI - Anaerobiosis and a theory of growth line formation. AB - Microstructural growth increments within the shells of numerous Recent and fossil molluscs are interpreted as reflections of alternating periods of shell deposition and dissolution, occurring during aerobic and anaerobic respiration, respectively. The acidic end products of anaerobic metabolism are neutralized by calcium carbonate from the shell, leaving a relatively insoluble organic residue at the mantle-shell interface. With the return of oxygenated conditions and resumption of aerobic respiration, this organic material is reincorporated within the shell. Inasmuch as metabolic changes are often synchronized with lunar or solar cycles (or both), we are led to the nearly paradoxical conclusion that, as a result of shell destructive processes, a relatively complete and detailed record of both short- and long-term growth is often preserved within the molluscan exoskeleton. Analyses of relationships between ambient oxygen concentrations and shell structural types may eventually prove useful, in paleoecological studies, for determination of dissolved oxygen gradients in Phanerozoic marine environments. PMID- 17741687 TI - Creative penmanship in animal testing prompts FDA controls. AB - Inaccurate science, sloppy science, fraudulent science-these are the greatest threats to the health and safety of the American people. Whether the science is wrong because of clerical error, or because of poor technique, or because of incompetence, or because of negligence, is less important than the fact that it is wrong. For if it is wrong, and if the FDA did not know it was wrong, then the protective regulatory barrier between a potentially dangerous drug and the patient is removed.-SENATOR EDWARD KENNEDY (D-Mass.), in congressional hearings on preclinical testing. PMID- 17741689 TI - Science in europe/attack on marxists stirs controversy. PMID- 17741688 TI - As luck would have it . . PMID- 17741690 TI - Laetrile at sloan-kettering: a question of ambiguity. PMID- 17741691 TI - A Mixed Verdict on NBC Nuclear Waste Documentary. PMID- 17741692 TI - Waterfowl hunters must give up lead shot. PMID- 17741693 TI - More burning of coal offsets gains in air pollution control. PMID- 17741694 TI - Big astronomy in chile: the southern observatories come of age. PMID- 17741695 TI - Carso. PMID- 17741696 TI - Ctio. PMID- 17741697 TI - Eso. PMID- 17741698 TI - Annual meeting washington. PMID- 17741699 TI - Teratogenicity: an epidemiological study. PMID- 17741701 TI - Neuropeptides. PMID- 17741702 TI - Fused cells. PMID- 17741700 TI - Acridology in the uvarovian style. PMID- 17741703 TI - Meteorite impact ejecta: dependence of mass and energy lost on planetary escape velocity. AB - The calculated energy efficiency of mass ejection for iron and anorthosite objects striking an anorthosite planet at speeds of 5 to 45 kilometers per second decreases with increasing impact velocity at low escape velocities. At escape velocities of >10(5) and >2 x 10(4) centimeters per second, respectively, the slower impactors produce relatively less ejecta for a given impact energy. The impact velocities at which ejecta losses equal meteorite mass gains are found to be approximately 20, 35, and 45 kilometers per second for anorthosite objects and approximately 25, 35, and 40 kilometers per second for iron objects striking anorthosite surfaces for the gravity fields of the moon, Mercury, and Mars. PMID- 17741704 TI - Evidence for a pollination-drop mechanism in paleozoic pteridosperms. AB - A noncellular substance containing pollen and spores has been discovered protruding from the micropyle of a seed fern ovule of Middle Pennsylvanian age. This provides direct evidence that pollination-drop mechanisms comparable to those of many extant gymnosperms characterize some Paleozoic pteridosperms. PMID- 17741706 TI - Oxygen isotopic analysis of the size fraction between 62 and 250 micrometers in Caribbean cores p6304-8 and p6304-9. AB - Oxygen isotopic analysis of the carbonate sediment fraction between 62 and 250 micrometry yields curves following the general trend of those obtained from Globigerinoides sacculifera. Warm stages 11, 13, and 15 are characterized by heavy postdepositional solution. which makes the sediment fraction between 62 and 250 micrometers rich in shell fragments of the more resistant, deeper-living species. As a result, oxygen isotopic analysis of these samples yields comparatively low temperatures, in contrast to those obtained from Globigerinoides sacculifera. PMID- 17741705 TI - Calcium oxalate: occurrence in soils and effect on nutrient and geochemical cycles. AB - Whewellite and weddellite, calcium salts of oxalic acid, have been found in the litter layer of several different soils, indicating that oxalate is a major metabolic product of fungi in natural environments. The presence of oxalate in soil solution speeds weathering of soil minerals and increases the availability of nutrients to vegetation. PMID- 17741708 TI - Potassium accumulation frog muscle: the association-induction hypothesis versus the membrane theory. PMID- 17741707 TI - Chemical evidence for separating the psilotaceae from the filicales. AB - The distribution of flavonoid compounds in Psilotum, Tmesipteris, and primitive filicalean ferns shows that it is unlikely the two groups are closely related. The Psilotaceae synthesize only amentoflavone and related biflavonyls which are totally absent from ferns. The primitive ferns contain the full complement of flavonols and proanthocyanidins, as found in all other filicalean families. PMID- 17741709 TI - PRODUCTS and MATERIALS. PMID- 17741710 TI - Prigogine at the university of Texas. PMID- 17741711 TI - THE RESEARCH CHEMIST, MANKIND'S DEVOTED AND INDISPENSABLE SERVANT. PMID- 17741712 TI - CONSPICUOUS ASTRONOMICAL ADVANCES OF THE YEAR. PMID- 17741713 TI - CONCERNING A NAME FOR BOTTOM MUD FOOD. PMID- 17741714 TI - NEW LOCALITIES FOR THE BLACK WIDOW SPIDER. PMID- 17741715 TI - SIGNIFICANT FIGURES IN STATISTICAL CONSTANTS. PMID- 17741716 TI - BENTHOS, BENTHIC AND "BENTHOTIC". PMID- 17741717 TI - THE CANCER SYMPOSIUM OF THE MEDICAL SCIENCES SECTION. PMID- 17741718 TI - FOOD OF MUD-DWELLERS. PMID- 17741720 TI - POSSIBILITY OF PARTHENOGENESIS IN GRASS. PMID- 17741719 TI - NITRIFICATION IN PRESENCE OF ORGANIC MATTER. PMID- 17741721 TI - PHOTOCHEMICAL OXIDATION OF AMMONIA IN SEA WATER. PMID- 17741722 TI - STOP-COCKS FOR MECHANICAL OPERATION. PMID- 17741723 TI - SIMPLE AID FOR COUNTING CROWDED PLATES. PMID- 17741724 TI - FIXATION OF SESSILE ROTATORIA. PMID- 17741725 TI - SOME ASPECTS OF PROGRESS IN MODERN ZOOLOGY. PMID- 17741726 TI - NATIONAL ACADEMIES AND THE PROGRESS OF RESEARCH. II. PMID- 17741727 TI - THE TEACHING OF THE HISTORY OF SCIENCE. PMID- 17741728 TI - ALBINISM IN THE ENGLISH SPARROW. PMID- 17741729 TI - NOTE ON AMOEligBA CLAVELLINAe NOV. SP. PMID- 17741730 TI - GONIONEMUS MURBACHII MAYER. PMID- 17741732 TI - FIRST EXPLORATION OF AN ALASKAN GLACIER. PMID- 17741731 TI - THE FORSYTH DENTAL INFIRMARY FOR CHILDREN. PMID- 17741733 TI - AN EARLY OBSERVATION ON THE RED SUNFLOWER. PMID- 17741734 TI - A REMARKABLE MICROSAUR FROM THE COAL MEASURES OF OHIO. PMID- 17741735 TI - THE OHIO ACADEMY OF SCIENCE. PMID- 17741736 TI - THE PRODUCTION OF SOUND BY RADIANT ENERGY. PMID- 17741737 TI - CONTRIBUTIONS TO COMPARATIVE PSYCHOLOGY. PMID- 17741738 TI - ASTRONOMY: The Morrison Observatory. PMID- 17741739 TI - FURTHER NOTES ON THE BRAIN OF THE SAUROPSIDA. PMID- 17741740 TI - THE VIEWS OF DR. HOLMES UPON THE PROPOSED REVISION MODIFICATIONS OF ANATOMICAL NOMENCLATURE. PMID- 17741741 TI - LOCUSTS AND SUN SPOTS. PMID- 17741743 TI - SCIENCE NEWS. PMID- 17741742 TI - A CURIOUS EGG. PMID- 17741744 TI - SOME ASPECTS OF FOREST BIOLOGY. PMID- 17741745 TI - JAPAN HONORS CHINA. PMID- 17741746 TI - CYTOGENETIC NOTES ON COTTON AND COTTON RELATIVES. PMID- 17741747 TI - ON THE INCIDENCE OF COLOR-BLINDNESS AMONG NEGROES. PMID- 17741748 TI - TOXICITY OF CADMIUM TO CHEWING INSECTS. PMID- 17741750 TI - A MELTING POINT APPARATUS FOR MINUTE SAMPLES. PMID- 17741749 TI - THE TWELFTH INTERNATIONAL VETERINARY CONGRESS. PMID- 17741751 TI - LABORATORY STIRRERS. PMID- 17741752 TI - THE BIOLOGICAL EFFECTS OF THYMUS EXTRACT (HANSON). PMID- 17741753 TI - ISOLATION OF THE INFECTIVE PRINCIPLE OF VIRUS DISEASES. PMID- 17741754 TI - Education and Strategy. PMID- 17741755 TI - News of Science. PMID- 17741756 TI - Paul E. Klopsteg, President-Elect. PMID- 17741758 TI - Public Information Service. PMID- 17741757 TI - Indianapolis Meeting in Retrospect. PMID- 17741759 TI - Mathematics (Section A). PMID- 17741761 TI - Chemistry (Section C). PMID- 17741760 TI - Mathematics (Section A). PMID- 17741762 TI - Physics (Section B). PMID- 17741763 TI - National Speleological Society (E4). PMID- 17741764 TI - Geology and Geography (Section E). PMID- 17741765 TI - Astronomical League (D2). PMID- 17741766 TI - Astronomy (Section D). PMID- 17741767 TI - American Association of Clinical Chemists (C1). PMID- 17741768 TI - Society of Systematic Zoology (F2). PMID- 17741769 TI - Zoological Sciences (Section F). PMID- 17741770 TI - Botanical Sciences (Section G). PMID- 17741771 TI - National Association of Biology Teachers (FG6). PMID- 17741772 TI - Ecological Society of America (FG4). PMID- 17741773 TI - Biometric Society, Eastern North American Region (FG3). PMID- 17741774 TI - Beta Beta Beta Biological Society (FG2). PMID- 17741776 TI - Psychology (Section I). PMID- 17741775 TI - Social and Economic Sciences (Section K). PMID- 17741777 TI - American Sociological Society (K4). PMID- 17741778 TI - History and Philosophy of Science (Section L). PMID- 17741779 TI - American Statistical Association (K5). PMID- 17741780 TI - Medical Sciences (Section N). PMID- 17741781 TI - General Systems Research (L2). PMID- 17741782 TI - Dentistry (Section Nd). PMID- 17741783 TI - Pharmacy (Section Np). PMID- 17741785 TI - Agriculture (Section O). PMID- 17741784 TI - Industrial Science (Section P). PMID- 17741786 TI - Society for Industrial Microbiology, Washington Section (P2). PMID- 17741788 TI - Conference on Scientific Manpower (X5). PMID- 17741787 TI - Education (Section Q). PMID- 17741790 TI - SCIENCE NEWS. PMID- 17741789 TI - EQUIPMENT NEWS. PMID- 17741791 TI - BOTANICAL RESEARCH. PMID- 17741792 TI - PROTECTIVE RESEMBLANCES IN INSECTS--EXPERIMENT AND THEORY. PMID- 17741793 TI - A NEW TERM FOR THE YOUTHFUL STAGE OF FORAMINIFERAL SHELLS. PMID- 17741794 TI - THE IMPORTANCE OF DIAMETER AS A FACTOR IN MYELINATION. PMID- 17741796 TI - SOME NOTES ON NORTH AMERICAN CRAYFISH. PMID- 17741795 TI - THE EXISTENCE OF A MONTHLY SEX CYCLE IN THE HUMAN MALE. PMID- 17741797 TI - MILTON AND CLARK AWARDS. PMID- 17741798 TI - CENTRALIZING BELL SYSTEM RESEARCHES. PMID- 17741799 TI - THE TEXAS ENTOMOLOGICAL SOCIETY. PMID- 17741800 TI - THE NEW ORLEANS ACADEMY OF SCIENCES. PMID- 17741801 TI - A FOOT-FOCUSSING DEVICE FOR THE BINOCULAR DISSECTING MICROSCOPE. PMID- 17741802 TI - VIRGINIA SOCIETY OF ORNITHOLOGY. PMID- 17741803 TI - A SIMPLE AND INEXPENSIVE RESPIRATOR FOR SMALL ANIMALS. PMID- 17741804 TI - INFRA-RED ABSORPTION OF WATER FRESHLY PREPARED FROM ICE AND FROM STEAM. PMID- 17741805 TI - THE EFFECT OF HEAVY WATER OF LOW CONCENTRATION ON EUGLENA. PMID- 17741806 TI - EFFECTS OF SOIL TEMPERATURE ON THE ABSORPTION OF WATER BY PLANTS. PMID- 17741808 TI - SCIENCE NEWS. PMID- 17741807 TI - GOSSYPOL, A CAUSE OF DISCOLORATION IN EGG YOLKS. PMID- 17741809 TI - THE EARLIEST KNOWN AMERICAN ARITHMETIC. PMID- 17741811 TI - ELLSWORTH BETHEL. PMID- 17741810 TI - THE SCIENTIFIC METHOD AND AUTHORITY. II. PMID- 17741813 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17741812 TI - SUPPORT OF THE U. S. GEOLOGICAL SURVEY AND OTHER COOPERATING AGENCIES. PMID- 17741814 TI - LOSSES IN TROUT FRY AFTER DISTRIBUTION. PMID- 17741815 TI - EVOLUTION AND THE UNIVERSITY OF NEBRASKA. PMID- 17741816 TI - THE FOURTH EDITION OF THE BIOGRAPHICAL DIRECTORY OF THE AMERICAN MEN OF SCIENCE. PMID- 17741817 TI - WORK ON SPHENODON. PMID- 17741818 TI - A SIMPLE METHOD FOR MAKING DIFFERENTIAL COUNTS OF SMALL SPORES. PMID- 17741819 TI - A PRELIMINARY REPORT ON THE CULTIVATION OF THE MICROBE OF OROYA FEVER. PMID- 17741820 TI - CULTURE MEDIUM FOR THE CILIATE LACRYMARIA. PMID- 17741822 TI - THE ELECTRO-MAGNET. PMID- 17741821 TI - SEASONAL AND REGIONAL VARIATIONS IN CURLY-TOP OF SUGAR BEETS. PMID- 17741823 TI - WHEAT SMUT. PMID- 17741825 TI - Long-Immersed Human Subjecst. PMID- 17741824 TI - AN IMPORTANT MEETING OF MINING AND METALLURGICAL ENGINEERS. PMID- 17741826 TI - Some Cases of Prolonged Want of Food. PMID- 17741827 TI - Impurities under Finger-Nails. PMID- 17741829 TI - Medical Students Abroad. PMID- 17741828 TI - HEALTH MATTERS. PMID- 17741830 TI - The Unit Measure of Time. PMID- 17741831 TI - On the Minerals contained in a Kiowa County (Kansas) Meteorite. PMID- 17741832 TI - Imaginary Tour. PMID- 17741833 TI - Modifying Weather on a Large Scale: Current proposals are either impractical or likely to produce cutes that are worse than the ailment. PMID- 17741835 TI - News of Science: War Prevention and International Cooperation: Statement of Third Pugwash Conference of Nuclear Scientists, Austria, 14-21 September. PMID- 17741834 TI - The Test of Simplicity: Simplicity is a test of the effectiveness of scientific theories; but what is the test of simplicity? PMID- 17741836 TI - Erratum. AB - In the article "Pavlov and Lamarck," by G. Razran [Science 128, 758 (3 Oct. 1958)], the quotation given in the first sentence of the section "Oral comments" (p. 760) should have read: "Pavlov remarked to me that one of the biggest scientific errors of his life was his assertion that acquired habits could be inherited," instead of ". . . could not be inherited." PMID- 17741837 TI - Cultures of Gonads of. PMID- 17741839 TI - Psychological Brightness Reduction of Simulated Flashes from a Polyhedral Satellite. PMID- 17741838 TI - Quantitave Relations between Stages of Leaf Development and Differentiation of Sieve Tubes. PMID- 17741840 TI - Artificially Induced Circulation of Lakes by means of Compressed Air. AB - Turbulence induced by air bubbles causes circulation in small thermally stratified lakes. Tests were made under summer and winter (ice-cover) conditions. Homoiothermal conditions, isometric concentrations of phosphorus, and increases of dissolved oxygen were achieved, at various rates of treatment. The application of the technique for lake management and in studies of lake dynamics is suggested. PMID- 17741841 TI - Thermocouple for Vapor Pressure Measurement in Biological and Soil Systems at High Humidity. PMID- 17741843 TI - Equipment. PMID- 17741844 TI - The New Mathematics. PMID- 17741845 TI - Atmospheres of Other Planets: Much has recently been discovered about the atmospheres of the planets, but some puzzles remain. PMID- 17741846 TI - News of Science. PMID- 17741847 TI - New Property of the Crystalline Style of Crassostrea virginica. PMID- 17741848 TI - New Excited State of Chlorophyll. PMID- 17741849 TI - Vulcanization with Tetramethylthiuram Disulfide. PMID- 17741850 TI - Hydrothermal Recrystallization of Molybdenum Trioxide. PMID- 17741852 TI - Equipment. PMID- 17741854 TI - ON THE EFFECTS OF DISEASE AND SENILITY AS ILLUSTRATED IN THE BONES AND TEETH OF MAMMALS. PMID- 17741853 TI - LOUIS AGASSIZ. PMID- 17741855 TI - AMERICAN METROLOGICAL SOCIETY. PMID- 17741856 TI - THE APPRENTICESHIP QUESTION. PMID- 17741857 TI - HENRY L. WHITING. PMID- 17741858 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17741860 TI - ASTRONOMICAL NOTES. PMID- 17741859 TI - ZOOLOGICAL NOTES. PMID- 17741861 TI - LIEUTENANT PEARY'S EXPEDITION. PMID- 17741862 TI - COLOR-BLINDNESS AND WILLIAM POLE: A STUDY IN LOGIC. PMID- 17741863 TI - Krilium. PMID- 17741864 TI - Structure and Properties of Ice. PMID- 17741865 TI - Uracil Protection against Ultraviolet Radiation Damage to a Higher Plant. PMID- 17741867 TI - Metabolic Relationship between Meso-Inositol and Lindane. PMID- 17741866 TI - Effect of Phosphorylated Hesperidin, a Hyaluronidase Inhibitor, on Fertility in the Rat. PMID- 17741868 TI - Serological Differentiation of Fish Bloods. PMID- 17741869 TI - Geography at Harvard. PMID- 17741870 TI - Lobbyist for American Science. PMID- 17741871 TI - Radiation Sensitivity of Benzene-d6. PMID- 17741872 TI - Computer encryption: key size. PMID- 17741873 TI - NBS: Problems and Needs. PMID- 17741874 TI - NBS: Problems and Needs. PMID- 17741875 TI - Raymond lindeman and the trophic-dynamic concept in ecology. AB - Lindeman's classic paper on energy flow in ecosystems was initially rejected for publication in Ecology. Reviewers felt there were insufficient data to support the theoretical model and that theoretical essays were inappropriate for Ecology. The paper was subsequently accepted by Thomas Park, the zoological editor, after correspondence with G. Evelyn Hutchinson who indicated the importance of theory in the development of ecology. PMID- 17741877 TI - The empathic computer. PMID- 17741876 TI - Carl rogers: giving people permission to be themselves. PMID- 17741879 TI - Issue of technology transfer is snag for 1979 u.N. Meeting. PMID- 17741878 TI - Robert thorne: controversial nominee for energy R & d job. PMID- 17741880 TI - VA Hospital System Under Scrutiny. PMID- 17741881 TI - Cooking up a Nutritional Lobby. PMID- 17741882 TI - Mental health. PMID- 17741883 TI - The zeeman effect: a unique approach to atomic absorption. PMID- 17741884 TI - Amaranth: a comeback for the food of the aztecs? PMID- 17741886 TI - 1978 AAAS Annual Meeting 12-17 February, Washington, D.C. PMID- 17741885 TI - Bacterial genetics: action at a distance on DNA. PMID- 17741887 TI - Nairobi conferees identify desertification indicators. PMID- 17741888 TI - Marine science session highlights annual interciencia meeting. PMID- 17741889 TI - Affiliate news. PMID- 17741890 TI - $185,000 in grants for project on handicapped. PMID- 17741891 TI - Women in Scientific Research Topic of AAAS Conference. PMID- 17741893 TI - Marine ecosystems. PMID- 17741892 TI - Survival strategies of the maya. PMID- 17741894 TI - Plant-parasite interactions. PMID- 17741895 TI - Viral diseases. PMID- 17741896 TI - Two-billion-year granulites in the late precambrian metamorphic basement along the southern peruvian coast. AB - Uranium-lead data indicate that the high-pressure granulitic and charnockitic nuclei within the medium-grade metamorphic complex of the Peruvian coastal area must be related to an orogenic event 2 x 10(9) years ago. As in western Africa and Brazil, this old granulitic basement is reworked by Late Precambrian orogeny. Its presence along the Peru-Chile Trench must be taken into account in interpreting the anomalously high strontium isotopic ratios of recent calc alkaline volcanism. PMID- 17741898 TI - ON THE SUPERFICIAL VISCIDITY OF LIQUIDS. PMID- 17741897 TI - Imitation of facial and manual gestures by human neonates. AB - Infants between 12 and 21 days of age can imitate both facial and manual gestures; this behavior cannot be explained in terms of either conditioning or innate releasing mechanisms. Such imitation implies that human neonates can equate their own unseen behaviors with gestures they see others perform. PMID- 17741899 TI - ON THE STRUCTURE OF THE ORANG OUTANG. PMID- 17741900 TI - NIMRAVID.E AND MIOCENE CANIDAE. PMID- 17741901 TI - ON THE ORIGIN OF ANTHRACITE. PMID- 17741903 TI - APPLICATION OF THE PHOTOPHONE TO THE STUDY OF THE NOISES TAKING PLACE ON THE SURFACE OF THE SUN. PMID- 17741902 TI - LECTURE PHOTOPHONE. PMID- 17741904 TI - ELECTRO-MOTIVE FORCE OF THE BRUSH DYNAMO-ELECTRIC MACHINE. PMID- 17741905 TI - ON PHOTOGRAPHING THE NEBULA IN ORION. PMID- 17741906 TI - To the Editor of Science. PMID- 17741907 TI - MICROSCOPY. PMID- 17741908 TI - ASTRONOMY: SWIFT'S COMET. PMID- 17741909 TI - BOTANY. PMID- 17741911 TI - CHEMICAL NOTES. PMID- 17741910 TI - PHYSICAL NOTES. PMID- 17741912 TI - Letters to the Editor. PMID- 17741913 TI - How Children Learn to Read. PMID- 17741914 TI - Who Reads the Journals? PMID- 17741915 TI - Half-Life of Radiocarbon. PMID- 17741916 TI - Television Coverage of the Gemini Program. PMID- 17741917 TI - Solar Magnetic Fields. PMID- 17741918 TI - Ant Venoms, Attractants, and Repellents. PMID- 17741919 TI - Hospital Discrimination: HEW Criticized by Civil Rights Groups. PMID- 17741920 TI - Space: MOL to Give Military First Chance at Manned Flight; Soviet Reaction Unpredictable. PMID- 17741921 TI - Sands of the Mid-Atlantic Ridge. AB - Sands collected at 24 locations along the crest of the Mid-Atlantic Ridge between 57 degrees S and 38 degrees N consist predominantly of olivine, diopsidic augite, hypersthene, enstatite, amphibole, quartz, plagioclase, and volcanic glass, suggesting an olivine tholeiitic source. Eight cores contain relatively pure mineral sands; three of these cores reflect local volcanic activity. In 16 cores the manganese-coated mineral grains are mixed in a current-winnowed foraminiferal sand or ooze. PMID- 17741922 TI - Enrichment of Tritium by Thermal Diffusion and Measurement of Dated Antarctic Snow Samples. AB - A thermal diffusion column allows a recovery of 99+/-1 percent of the tritium originally contained in about 50 liters at standard temperature and pressure of hydrogen gas in a final volume of 3.8 liters over a 2-day period. After a tenfold enrichment by electrolysis, a tritium concentration of 10(-18) with an experimental error of a few percent may be measured with a low-level Geiger counter. The results on some well-dated Antarctic snow samples (between 1941 and 1953) are in general agreement with published data. PMID- 17741923 TI - Angiosperm Parasite and Host: Coordinated Dispersal. AB - Seeds of the root parasite Orthocarpus densiflorus may be dispersed by the propagules of its host, Hypochoeris glabra. Such coordinated transport, which includes seed clustering, reinforces the integration and stability of populations of this host and parasite. PMID- 17741924 TI - Stridulation in Leaf-Cutting Ants. AB - The leaf-cutting ant Atta caphaloes L. stridulates whenever it is prevented from moving freely. Although audible to the human ear, the airborne sound produced has its main energy concentrated between 20 and 60 kilocycles per second. However, it is not the airborne, but the groundconducted stridulation sound that acts as a distress alarm: a stridulating ant attracts other workers, and if the "calling" ant is covered by earth, intensive digging is released in the attracted nest mates. PMID- 17741925 TI - Forthcoming Events. PMID- 17741926 TI - Electromagnetic Scattering. PMID- 17741927 TI - THE BRITISH ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE SOME ASPECTS OF MODERN PETROLOGY. PMID- 17741928 TI - LETTER TO THE SECRETARY OF AGRICULTURE DISMISSING THE CHARGES AGAINST OFFICERS OF THE BUREAU OF CHEMISTRY. PMID- 17741929 TI - PROFESSOR JOSIAH KEEP. PMID- 17741930 TI - A NEW NATIONAL MATHEMATICAL SOCIETY. PMID- 17741931 TI - THE AMERICAN MINING CONGRESS. PMID- 17741932 TI - AGRICULTURAL RESEARCH IN GREAT BRITAIN. PMID- 17741934 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17741933 TI - HONORARY DEGREES AT THE UNIVERSITY OF ST. ANDREWS. PMID- 17741936 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17741935 TI - THE GRAND CANYON OF THE COLORADO. PMID- 17741937 TI - DRAUGHTS AND COLDS. PMID- 17741938 TI - MEDICAL PRACTISE IN GREAT BRITAIN. PMID- 17741939 TI - BLANDING'S TURTLE. PMID- 17741940 TI - RANDOM SEGREGATION VERSUS COUPLING IN MENDELIAN INHERITANCE. PMID- 17741942 TI - EMERGENT EVOLUTION AND THE SOCIAL. PMID- 17741941 TI - SCIENCE NEWS. PMID- 17741943 TI - THE TONGA EXPEDITION OF 1926. PMID- 17741944 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17741945 TI - HOOKE'S LAW: A REJOINDER. PMID- 17741946 TI - SCABLAND MOUNDS OF EASTERN WASHINGTON. PMID- 17741947 TI - A HERMAPHRODITIC VIVIPAROUS OYSTER OF THE ATLANTIC COAST OF NORTH AMERICA. PMID- 17741948 TI - FURTHER ON AERIAL SOUNDS IN YELLOWSTONE PARK. PMID- 17741949 TI - A RAPID IRON HAEMATOXYLIN TECHNIQUE. PMID- 17741950 TI - THE EFFECT OF PRESSURE ON THE MAGNETIZATION OF MAGNETITE. PMID- 17741951 TI - PRELIMINARY NOTE ON THE EGG AND LARVA OF THE AMERICAN EEL (ANGUILLA ROSTRATA). PMID- 17741953 TI - THE WORLD'S FORESTRY CONGRESS. PMID- 17741952 TI - ACIDOSIS, TREMBLES AND MILKSICKNESS. PMID- 17741954 TI - SCIENCE NEWS. PMID- 17741955 TI - THE ADVANCEMENT OF ENGINEERING IN RELATION TO THE ADVANCEMENT OF SCIENCE. PMID- 17741957 TI - A SUGGESTED COURSE OF STUDY FOR MEDICAL TECHNICIANS. PMID- 17741956 TI - SOME PSYCHOLOGICAL EXPERIMENTS II. PMID- 17741958 TI - MILLIKAN RAYS AND THE ACCELERATION OF RADIOACTIVE CHANGE. PMID- 17741959 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17741960 TI - INSECT TOXICOLOGY. PMID- 17741961 TI - THE REQUIREMENT OF MATHEMATICS FOR COLLEGE FRESHMEN. PMID- 17741962 TI - A DILATOMETER FOR MEASURING THE HYDRATION OF COLLOIDS. PMID- 17741963 TI - DOES BACTERIOPHAGE RESPIRE? PMID- 17741964 TI - INHERITANCE OF ANTHOCYANIN IN CREPIS. PMID- 17741965 TI - High voltage accelerators. PMID- 17741966 TI - Ideal setting. PMID- 17741967 TI - Marvin gardens revisited. PMID- 17741968 TI - The hue massacre. PMID- 17741969 TI - Federal project grants. PMID- 17741970 TI - Letter to the editor. PMID- 17741971 TI - Adjusting to normal times. PMID- 17741972 TI - Superheavy Elements: Attempts to discover elements with about 114 protons have gained momentum with the use of new accelerators. PMID- 17741973 TI - Operations Research: Some Contributions to Mathematics: Applied mathematics gets a new surge of life from techniques of operations research. AB - The discussion of fuzzy sets indicates that set theory should be extended to make it more suitable for the development of algebraic structures with wider applications. Stochastic optimization, a synthesis of the three areas of continuum mathematics, is a rapidly growing field particularly in the context of control theory. Applications of discrete mathematics have found a rich outlet in graph theory, particularly in the social sciences. However, there remains a wide gap between the sophisticated activities that are required for the development of optimum policies and the more difficult and intractable problems of organizational structures and performance. PMID- 17741974 TI - AMA: Specialty Journals Must Lure Paying Subscribers. PMID- 17741975 TI - NAS Members Appeal on Behalf of Soviet Colleagues. PMID- 17741976 TI - New york university: learning to live with red ink. PMID- 17741977 TI - Los alamos: 30 years after, life begins in earnest. PMID- 17741978 TI - Science shuffle. PMID- 17741979 TI - Conservation of energy: the potential for more efficient use. PMID- 17741980 TI - Galilean satellites: identification of water frost. AB - Water frost absorptions have been detected in the infrared reflectivities of Jupiter's Galilean satellites JII (Europa) and JIII (Ganymede). We have determined the percentage of frost-covered surface area to be 50 to 100 percent for JII, 20 to 65 percent for JIII, and possibly 5 to 25 percent for JIV (Callisto). The leading side of JIII has 20 percent more frost cover than the trailing side, which explains the visible geometric albedo differences between the two sides. The reflectivity of the material underlying the frost on JII, JIII, and JIV resembles that of silicates. The surface of JI (Io) may be covered by frost particles much smaller than those on JII and JIII. PMID- 17741981 TI - Internal gravity wave-atmospheric wind interaction: a cause of clear air turbulence. AB - The interaction between an internal gravity wave and a vertical wind shear may be responsible for the production of clear air turbulence in the free atmosphere. A simplified model equation demonstrates the feasibility of the suggested mechanism. PMID- 17741982 TI - Obsidian trade routes in the mayan area. AB - Obsidian from two sources in highland Guatemala has been found at 23 sites of the Classic Mayan civilization, mainly in the nonvolcanic lowlands to the north. The distribution, together with trade routes suggested by topography and documentary sources, suggests efficient waterborne transport and competition between sources for the lowland market. PMID- 17741983 TI - Saltbush leaves: excision of hypersaline tissue by a kangaroo rat. AB - Dipodomys microps climbs into shrubs and harvests leaves of the halophyte Atriplex confertifolia throughout the year. The epidermal vesicles of these leaves are high in electrolyte concentration, but the specialized photosynthetic parenchyma which is arranged concentrically about the vascular bundles is low in electrolytes and high in starch. The lower incisors of D. microps are broad, flattened anteriorly, and chisel-shaped (unlike those of other kangaroo rats, which are rounded and awl-shaped) and are used to shave off the hypersaline, peripheral tissue of the leaves so that the inner tissue can be eaten. This atypical feeding behavior should minimize the reliance of D. microps on the unpredictable seed crops of desert annuals, and also favor its coexistence with other species of Dipodomys, which are primarily granivorous. PMID- 17741984 TI - Object distance as a determinant of visual fixation in early infancy. AB - Data from two experiments show that the duration of visual fixation of solid objects by infants aged 6 to 20 weeks varies as a function of object distance between 30 and 90 centimeters. There was no characteristic habituation of fixation of an object at 90 centimeters but there was a marked increase in fixation time when objects were advanced to 30 centimeters (experiment 1). A linear decline in fixation times occurred as the object distance increased from 30 to 90 centimeters with the real size and the angular size of the object held constant (experiment 2). No evidence for visual size constancy in young infants was obtained by this method. PMID- 17741986 TI - Time reversal and irreversibility. PMID- 17741985 TI - Electrodynamic sailing: beating into the solar wind. PMID- 17741987 TI - Organization of energy-transducing membranes: report of a joint Japan-United States seminar. PMID- 17741988 TI - Astronomy and air pollution. PMID- 17741990 TI - PLEISTOCENE CLAYS AS A CHRONOMETER. PMID- 17741989 TI - CONSERVATION OF THE QUALITY OF WATER OF NEW YORK STATE AS A NATURAL RESOURCE. PMID- 17741991 TI - GENERAL RESOLUTIONS OF THE PANPACIFIC SCIENTIFIC CONFERENCE. PMID- 17741992 TI - MIRAGES? PMID- 17741994 TI - THE NEEDS OF MEN OF SCIENCE IN RUMANIA. PMID- 17741993 TI - FAMILY AND SUBFAMILY NAMES IN ZOOLOGY. PMID- 17741995 TI - THE SOUNDS OF SPLASHES. PMID- 17741996 TI - THE CRYSTAL STRUCTURE OF ICE. PMID- 17741997 TI - THE AMERICAN CHEMICAL SOCIETY. VIII. PMID- 17741999 TI - AMYLOSE: ITS CONSTITUENTS AND METHODS FOR THEIR ESTIMATION. PMID- 17741998 TI - ON COMETARY APPEARANCES. PMID- 17742000 TI - A REMARKABLE INVASION OF NORTHERN NEW YORK, BY A PYRALID INSECT. PMID- 17742001 TI - CANcaronONS--THEIR CHARACTER AND ORIGIN. PMID- 17742003 TI - TRICHINAe CYSTS. PMID- 17742002 TI - ADDRESS OF COL. GARRICK MALLERY, U. S. ARMY. AB - It may be conceded that after man had all his present faculties, he did not choose between the adoption of voice and gesture, and never with those faculties, was in a state where the one was used, to the absolute exclusion of the other. The epoch, however, to which our speculations relate is that in which he had not reached the present symmetric development of his intellect and of his bodily organs, and the inquiry is: Which mode of communication was earliest adopted to his single wants and informed intelligence? With the voice he could imitate distinictively but few sounds of nature, while with gesture he could exhibit actions, motions, positions, forms, dimensions, directions and distances, with their derivations and analogues. It would seem from this unequal division of capacity that oral speech remained rudimentary long after gesture had become an efficient mode of communication. With due allowance for all purely imitative sounds, and for the spontaneous action of vocal organs under excitement, it appears that the connection between ideas and words is only to be explained by a compact between speaker and hearer which supposes the existence of a prior mode of communication. This was probably by gesture. At least we may accept it as a clew leading out of the labyrinth of philological confusion, and regulating the immemorial quest of man's primitive speech. PMID- 17742004 TI - FISH HATCHERIES OF THE UNITED STATES. PMID- 17742005 TI - LIQUID FUEL FROM COAL. PMID- 17742006 TI - BERYLLIUM. PMID- 17742007 TI - LOCUST PODS FOR FODDER. PMID- 17742008 TI - CLADOCERA. PMID- 17742009 TI - X-RAYS AND EVOLUTION. PMID- 17742010 TI - TUBERCULOSIS VACCINE FOR CATTLE. PMID- 17742011 TI - ASIATIC CHOLERA. PMID- 17742012 TI - IRA REMSEN. PMID- 17742013 TI - THE RENO MEETING OF THE PACIFIC DIVISION--II. PMID- 17742014 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17742015 TI - PHILOSOPHY AND THE SCIENCES. PMID- 17742016 TI - THE JACOBS CAVERN MASTODON AGAIN. PMID- 17742017 TI - PHOTOMETRY. PMID- 17742018 TI - A NEW LOCALITY IN CHINA FOR LYTTONIA RICHTHOFENI KAYSER. PMID- 17742019 TI - THE SEX RATIO OF ADULT TRICHINAE. PMID- 17742020 TI - AWARDS FOR RESEARCH AT THE UNIVERSITY OF CALIFORNIA. PMID- 17742021 TI - DIETARY REQUIREMENTS FOR REPRODUCTION. PMID- 17742022 TI - LONG-BONE LENGTH AND BODY SIZES. PMID- 17742023 TI - Letter to the editor. PMID- 17742024 TI - Letter to the editor. PMID- 17742025 TI - Race and academic hiring. PMID- 17742027 TI - Letter to the editor. PMID- 17742026 TI - Margin of safety. PMID- 17742028 TI - Committee on chemotaxonomy. PMID- 17742030 TI - The evaluation of basic science. PMID- 17742029 TI - Letter to the editor. PMID- 17742031 TI - Plate tectonics in geologic history. PMID- 17742032 TI - Cancer Politics: NIH Backers Mount Late Defense in House. PMID- 17742034 TI - Soviet-american conference urges search for other worlds. PMID- 17742033 TI - Briefing. PMID- 17742036 TI - Outstanding science library to close. PMID- 17742035 TI - Black Lung: Dispute about Diagnosis of Miners" Ailment. PMID- 17742037 TI - Scientists meet coal miners. PMID- 17742038 TI - Caribbean eocene volcanism and the extent of horizon a. AB - Layer A and its correlative layer A" in the Caribbean have been interpreted as chert layers produced by Eocene volcanism. Exposures of Eocene volcanic rocks in Puerto Rico and the Dominican Republic may represent layer A interbedded with coarser volcanic debris and preserved near early Tertiary volcanic centers. PMID- 17742040 TI - 27 december the information-conscious society. PMID- 17742039 TI - Synchrony and flash entrainment in a new Guinea firefly. AB - Fireflies can duplicate both faster and slower rhythms of artificial light. Since the interval between the pacer signal and the firefly's flash of the next cycle approximates the firefly's normal free-run period, it is suggested that the pacer signal resets the flash-timing oscillator in the brain, thus providing a mechanism for synchronization. PMID- 17742041 TI - 28-29 december comparative immunology of the oral cavity. PMID- 17742042 TI - 28 december alternative approaches to national delivery of health care. PMID- 17742043 TI - Extending Symbiotic Nitrogen Fixation to Increase Man's Food Supply. PMID- 17742044 TI - MIDDLE SCHOOL ACHIEVEMENT: Asia Stays on Top, U.S. in Middle in New Global Rankings. AB - Eighth graders from the United States are still running in the middle of the global pack when it comes to science and math achievement, according to the latest results from the Third International Mathematics and Science Study. And Asian nations continue to lead the way, with Singapore and Taiwan emerging as the star performers among the 38 participating countries. The news is not good for U.S. science and math educators, who have spent much of the decade pursuing reforms aimed at raising student achievement. PMID- 17742045 TI - TOXICOLOGY: Panel Urges Further Study of Biotech Corn. AB - This fall, genetically modified corn that had not been approved for human consumption was found in taco shells in the United States. Last week, the U.S. Environmental Protection Agency (EPA) convened a scientific panel to review evidence on whether this StarLink corn could harm sensitive people by causing allergic reactions. The panel found that the overall probability is "low," but the EPA appears intent on investigating further before allowing the corn in foods, as its manufacturer has requested. PMID- 17742046 TI - INFECTIOUS DISEASES: Polio Outbreak Raises Questions About Vaccine. AB - A small cluster of polio cases in the Dominican Republic and Haiti marks both the first polio outbreak in the Western Hemisphere in more than 9 years and the first reliable report that a vaccine-derived polio strain may have reverted to a virulent form and spread contagiously. Although a massive vaccination campaign already in the works is expected to contain the outbreak, the unusual incident raises troubling questions about a vaccine that has been in widespread use for nearly 40 years. PMID- 17742047 TI - RESEARCH ETHICS: Studies Trace Patchwork of Conflict Policies. AB - For more than a year since the September 1999 death of a teenager in a gene therapy clinical trial that had industry connections, scientists, ethicists, and government and university officials have been fretting about conflict of interest. But no one could say just how the nation's universities are policing such conflicts. Now, three recently published studies show that requirements for disclosure of outside financial interests vary widely from university to university, as do penalties for violations. PMID- 17742048 TI - MARINE ENVIRONMENT: Clinton Creates Huge Hawaiian Coral Haven. AB - President Bill Clinton last week signed an executive order creating the Northwestern Hawaiian Islands Coral Reef Ecosystem Reserve. Marine scientists say that the megareserve, which holds nearly 70% of the nation's reefs, will help protect some of the globe's most pristine ocean habitats. PMID- 17742049 TI - CHEMISTRY: Crystals Branch Out Into Exotic Shapes. AB - Researchers recently managed to steer crystal growth to make thin rods by controlling the speed at which various faces of crystals grow. Now, a team has elevated this control to an art form, enabling them to make nanosized versions of a variety of shapes including rods, arrows, teardrops, and even four-armed tetrapods shaped like a child's jack. PMID- 17742050 TI - MATHEMATICS: Taking the Measure of the Wildest Dance on Earth. AB - By exploiting the symmetry of randomness, three mathematicians have revealed the geometric underpinnings of the frenetic random dance called Brownian motion. The methods they used seem likely to apply to other random processes, some as familiar as the flow of water through a filter. The proof was presented at the recent Current Developments in Mathematics 2000 conference sponsored by Harvard University and the Massachusetts Institute of Technology. PMID- 17742051 TI - AAS HIGH-ENERGY ASTROPHYSICS DIVISION: X-rays Hit the Spot for Astrophysicists. AB - About 500 astronomers flocked to Waikiki Beach from 6 to 10 November for a meeting of the American Astronomical Society's High-Energy Astrophysics Division. Looking splendid in their complimentary aloha shirts, speakers told tales of intense radiation from deep space, including x-rays from baby stars and from quasars, which could help refine estimates of how quickly the universe is expanding. PMID- 17742052 TI - How much does one vote count in an election? PMID- 17742054 TI - COMPUTING: Screen Savers of the World Unite! AB - Unused CPU time on desktop computers could be put to good use, if distributed computing succeeds in capturing people's imagination. In their Perspective, Shirts and Pande describe existing distributed computing projects and recent efforts to overcome parallelization problems. This vast underused resource could raise biological and other scientific computation to fundamentally new predictive levels. PMID- 17742053 TI - 'Kyoto forests' and a broader perspective on management. PMID- 17742055 TI - PALEOCLIMATE: Glacial Climate Instability. AB - Throughout the last glacial period, rapid climatic changes called Dansgaard Oeschger (D-O) events occurred in the Northern Hemisphere. As Labeyrie discusses in his Perspective, these events are ideal targets for testing our understanding of climate change and developing climatic change models. Important steps toward understanding D-O events, particularly regarding the role of the low latitudes, are now reported by Hughen et al. and Peterson et al. PMID- 17742056 TI - OPTICS: The Internet of Tomorrow. AB - The unsatiable demand for more bandwidth threatens to lead to the Internet's collapse. In his Perspective, Joiner explains that new optical technologies are the key to resolving both today's "last-mile" bottleneck and future intrasystem bottlenecks. At the core of the new technology lies the vertical cavity surface emitting laser. PMID- 17742057 TI - Piecing together the biggest puzzle of all. AB - In this month's essay, the last in the Pathways of Discovery series, Martin J. Rees celebrates the way astronomers and cosmologists have systematically uncovered the biography of the universe. Rife with neutron stars, black holes, and multiple universes that emerge from quantum fluctuation, it's a story as grand as it is strange. PMID- 17742058 TI - SCIENCE NEWS. PMID- 17742059 TI - FROM THE PONDERABLE TO THE IMPONDERABLE. PMID- 17742060 TI - THE HIGH COST OF GERMAN MEDICAL AND SCIENTIFIC PERIODICALS. PMID- 17742061 TI - IS LONGEVITY COMPATIBLE WITH OPTIMUM GROWTH? PMID- 17742062 TI - SOLUBLE SESQUIOXIDES AND ORGANIC MATTER FROM ALKALI TREATMENTS ON SOILS. PMID- 17742063 TI - A TWO-FIELD STROBOSCOPE. PMID- 17742065 TI - ACCELERATED, EXPERIMENTAL POLIOMYELITIS IN NASALLY INSTILLED MONKEYS. PMID- 17742064 TI - THE ATTRACTION OF SPHERES. PMID- 17742066 TI - REGULATING THE AIR SUPPLY OF MICRO BURNERS. PMID- 17742068 TI - AGRICULTURAL TEXT-BOOOKS FOR OUR PUBLIC SCHOOLS. PMID- 17742067 TI - EDUCATION, SCIENCE AND LEADERSHIP. PMID- 17742069 TI - FRED SILVER PUTNEY. PMID- 17742070 TI - VON ADOLF ERICH DAECKE. PMID- 17742071 TI - INSIDIOUS SCIENTIFIC CONTROL. PMID- 17742073 TI - QUOTATIONS. PMID- 17742072 TI - NEMATODES ON MARKETABLE FISHES. PMID- 17742074 TI - PAPERS "TO BE PUBLISHED". PMID- 17742076 TI - SPECIAL ARTICLES. PMID- 17742075 TI - BIRTH STATISTICS IN THE REGISTRATION AREA OF THE UNITED STATES: 1916. PMID- 17742077 TI - Acoustical Oscillations of Flames. PMID- 17742078 TI - The New Immigration Law. PMID- 17742079 TI - Leigh Page: 1884-1952. PMID- 17742080 TI - Fall in Minimum Night Temperature at or near Full Moon: Part II. PMID- 17742081 TI - Night Temperatures and the Moon. PMID- 17742082 TI - The holly oak pendant. PMID- 17742083 TI - In reply: the holly oak pendant. PMID- 17742084 TI - An Editor's Quest (II). PMID- 17742085 TI - Seismic verification of a comprehensive test ban. AB - The capabilities of in-country seismic monitoring systems for verifying the absence of underground nuclear explosions are compared against challenges posed by possible clandestine testing schemes. Although analysis indicate that extensive networks of in-country seismic arrays are needed to verify a Comprehensive Test Ban Treaty, such networks cannot ensure that all underground nuclear explosions will be identified. Political and military judgments will determine the level of risk acceptable to each nation. PMID- 17742086 TI - The World Bank's Support for Science and Technology. AB - The World Bank, the largest aid-granting agency in the world, has played a substantial but largely unsung role in helping the scientific and technological development of developing countries. Its investments, totaling $15.5 billion in fiscal year 1984, involve choosing appropriate technology and financing local technological development. Since 1980, the Bank has lent $0.5 billion for agricultural research and about $1 billion for scientific and technological education. It contributes to and mobilizes finances for large international research programs in agriculture and the health sciences. It supports research on labor-based construction, low-cost sanitation, renewable energy resources, and control of traffic congestion. It provides training in the technological aspects of development policy. As funds for aid become scarce, the Bank is reexamining its approach to science and technology. PMID- 17742087 TI - Europeans Set to Join in U.S. Space Station: Research ministers are expected to give their approval at a meeting later this month; many groups remain skeptical of the project's value. PMID- 17742088 TI - Virgin rain forest reprieved. PMID- 17742089 TI - Twin information bank. PMID- 17742090 TI - Telescope gets largest private gift ever. PMID- 17742091 TI - Empty space talk. PMID- 17742092 TI - A New Image for the Space Shuttle: The advent of the shuttle's first all-military flight highlights the Pentagon's long-standing influence on an ostensibly civilian program. PMID- 17742094 TI - Primate males and infants: primate paternalism. PMID- 17742093 TI - Astronomy and the Realities of the Budget: The Field Committee Report set forth a remarkable consensus on research priorities; but other disciplines have priorities too. PMID- 17742095 TI - Extracellular matrix: extracellular matrix biochemty. PMID- 17742096 TI - Cellular organelles: chloroplasts. PMID- 17742097 TI - Mistletoes: the biology of mistletoes. PMID- 17742098 TI - Subtropical atlantic climate studies: introduction. AB - This report is an introduction to the accompanying collection of reports that present the results of a 2-year period of intensive monitoring of the Florida Current. Both direct observing systems (ship-deployed current profilers and moored current meters) and indirect observing systems (coastal tide gauge stations, bottom pressure gauge arrays, a submarine cable, acoustic arrays, and radar installations) were used to measure temperature and volume transport. PMID- 17742100 TI - Florida current: low-frequency variability as observed with moored current meters during april 1982 to june 1983. AB - A 1-year time series of volume transport through the Florida Straits near 27 degrees N was derived from an array of five subsurface current meter moorings. The transport estimates, determined on the basis of constant shear extrapolation of the subsurface velocities to the surface, are in good agreement with transports derived from submarine cable and Pegasus measurements. The annual transport cycle in 1982-1983 is complicated by large-amplitude fluctuations on time scales of 1 to 3 weeks, but it does exhibit a transport maximum in summer and a minimum in fall-winter, consistent with historical results and of similar magnitude. The energy density spectrum of transports is continuous with a slope of about -1.5 and does not show a gap between the periods of weeks and seasonal. Evidence was found for atmospheric forcing of transport fluctuations, with highest coherence between transport and the local meridional wind stress at periods of 10 and 15 days during the summer and 5 and 40 days during the winter. PMID- 17742099 TI - Volume and heat transports of the Florida current: april 1982 through august 1983. AB - Absolute velocity and temperature profiles are used to estimate the volume transport through the Straits of Florida and, in combination with historical midbasin data, to estimate the total meridional heat flux through a section at 27 degrees N. The mean annual volume transport of the Florida Current from April 1982 through August 1983 is 30.5 (+/- 1)x 10(6) cubic meters per second. The net northward heat flux through the 27 degrees N section is 1.2 (+/- 0.1)x 10(15) watts. The volume transport is characterized by high values in the late spring and early summer and low values in the late fall and early winter. There is a similar cycle in total heat flux. PMID- 17742101 TI - Florida current volume transports from voltage measurements. AB - The volume transport of the Florida Current is determined from the motionally induced voltage difference between Florida and Grand Bahama Island. Simultaneous measurements of potential differences and of volume transport by velocity profiling have a correlation of 0.97. The calibration factor is 25+/- 0.7 sverdrups per volt, and the root-mean-square discrepancy is 0.7 sverdrup. The induced voltage is about one-half the open-circuit value, implying that the conductance of the sediments and lithosphere is about equal to that of the water column. PMID- 17742102 TI - Sea level variation as an indicator of Florida current volume transport: comparisons with direct measurements. AB - Sea level measurements from tide gauges at Miami, Florida, and Cat Cay, Bahamas, and bottom pressure measurements from a water depth of 50 meters off Jupiter, Florida, and a water depth of 10 meters off Memory Rock, Bahamas, were correlated with 81 concurrent direct volume transport observations in the Straits of Florida. Daily-averaged sea level from either gauge on the Bahamian side of the Straits was poorly correlated with transport. Bottom pressure off Jupiter had a linear coefficient of determination ofr(2) = 0.93, and Miami sea level, when adjusted for weather effects, had r(2) = 0.74; the standard errors of estimating transports were +/- 1.2 x 10(6) and +/- 1.9 x 10(6) cubic meters per second, respectively. A linear multivariate regression, which combined bottom pressure, weather, and the submarine cable observations between Jupiter and the Bahamas, had r(2) = 0.94 with a standard error of estimating transport of +/- 1.1 x 10(6) cubic meters per second. These results suggest that a combination of easily obtained observations is sufficient to adequatelv monitor the daily volume transport fluctuations of the Florida Current. PMID- 17742103 TI - Florida current: seasonal and interannual variability. AB - Annual and interannual variations in the Florida Current, Caribbean, and subtropical Atlantic are investigated with the use of historical sea level differences and wind field data. Observational and model evidence suggests that the seasonal transport cycle of the Florida Current is locally forced, either upstream in the Caribbean or downstream over topography. Although at seasonal and shorter periods sea level or bottom pressure fluctuations on the left side of the Florida Current contribute almost all of the variance of sea level difference across the Florida Straits and hence transport, this relation does not seem to apply at interannual time scales. Using results from the Subtropical Atlantic Climate Studies, it is estimated from historical sea level data that interannual transport fluctuations of the Florida Current are only of order 1 x 10(6) cubic meters per second. Interannual fluctuations in the 2- to 3-year period range in the Florida Straits seem to be correlated with sea level differences across the Caribbean and the subtropical Atlantic but not with Sverdrup transport fluctuations in the subtropical Atlantic. PMID- 17742104 TI - Individual and population shifts in flower color by scarlet gilia: a mechanism for pollinator tracking. AB - Individual plants and populations of scarlet gilia (Ipomopsis aggregata) shift from darker to lighter corolla colors during the flowering season. Shifts to lighter color coincide with emigration of hummingbirds from the system. In the absence of hummingbirds, lighter colors attract the remaining pollinator, a hawkmoth. Comparison of plants that shift to lighter colors with those that fail to shift shows that shifting is adaptive in that it enhances reproductive success because of the preference of hawkmoths for lighter colored flowers. Color shifting therefore provides a mechanism for plants to track changing pollinator abundances. PMID- 17742105 TI - THE TWENTY-EIGHTH GENERAL MEETING OF THE AMERICAN CHEMICAL SOCIETY. PMID- 17742106 TI - THE CASE FOR VACCINATION. PMID- 17742107 TI - ON USES OF A DRAWING BOARD AND SCALES IN TRIGONOMETRY AND NAVIGATION. PMID- 17742108 TI - METEOROLOGICAL OBSERVATIONS WITH KITES AT SEA. PMID- 17742109 TI - CRYSTALS OF OXALATE OF LIME IN PLANTS. PMID- 17742110 TI - THE SEMINAR METHOD IN NATURAL SCIENCES, ESPECIALLY IN ZOOLOGY. PMID- 17742111 TI - BOTANICAL NOTES. PMID- 17742112 TI - MODERN VIEWS ON MATTER. PMID- 17742113 TI - GRASSHOPPERS' PLAGUES. PMID- 17742114 TI - THE COMPOSITION OF MILK. PMID- 17742115 TI - GREEN LEAVES AND SUNSHINE. PMID- 17742116 TI - ORIGIN OF THE MAYA CALENDAR. PMID- 17742117 TI - IMPROVEMENTS IN TREE CROPS. PMID- 17742118 TI - INSECTS IN FIGHT ON CACTUS PEST. PMID- 17742119 TI - HEALTH SURVEYS BY THE MILBANK MEMORIAL FUND. PMID- 17742120 TI - THE SMITHSONIAN INSTITUTION--PARENT OF AMERICAN SCIENCE. PMID- 17742122 TI - LEONCE PIERRE MANOUVRIER. PMID- 17742121 TI - UNDERLYING FACTORS IN THE CONFUSION IN ZOOLOGICAL NOMENCLATURE WITH A DEFINITE PRACTICAL SUGGESTION FOR THE FUTURE. PMID- 17742123 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17742124 TI - PUBLICATION BY PHOTOGRAPHY. PMID- 17742125 TI - BACTERIAL FILTERS AND FILTERABLE VIRUSES. PMID- 17742126 TI - THE JOURNAL OF GENERAL PHYSIOLOGY. PMID- 17742128 TI - THE ELDEN PUEBLO. PMID- 17742127 TI - THE FRENCH SOCIETY FOR BIOGEOGRAPHY. PMID- 17742129 TI - ON THE ABSOLUTE ZERO OF THE CONTROLLABLE ENTROPY AND INTERNAL ENERGY OF A SUBSTANCE OR MIXTURE. PMID- 17742130 TI - THE WHALE-SHARK, RHINEODON TYPUS, IN THE GULF OF CALIFORNIA. PMID- 17742131 TI - The Neutron Pile as a Tool in Quantitative Analysis; The Gallium and Palladium Content of Iron Meteorites. PMID- 17742132 TI - Seven Decades of Nutrition Research. PMID- 17742133 TI - The Effectiveness of Dramamine in the Prevention of Airsickness. PMID- 17742134 TI - The Prevention and Treatment of Motion Sickness I. Seasickness. PMID- 17742135 TI - Application of Chromatography to the Separation of Subcellular, Enzymatically Active Granules. PMID- 17742136 TI - Chronic Toxicity of Gossypol. PMID- 17742137 TI - Lygus Bugs in Relation to the Occurrence of Embryoless Seeds in the Umbelliferae. PMID- 17742138 TI - A Metabolic Regulator in Mammalian Spermatozoa. PMID- 17742139 TI - Lack of Depolymerase Effect on Desoxyribonucleic Acid in Living Cells. PMID- 17742140 TI - THE PRESENT STATUS OF THE HISTORY OF SCIENCE IN AMERICAN COLLEGES AND UNIVERSITIES. PMID- 17742141 TI - THE EXPEDITION TO TRINIDAD FOR THE STUDY OF HOOKWORM DISEASE. PMID- 17742142 TI - THE TORONTO MEETING. PMID- 17742143 TI - IN ASSISTANCE OF THE ARCHIVES DE BIOLOGIE. PMID- 17742144 TI - THE VIBRATIONS OF A TUNING FORK. PMID- 17742145 TI - TWO RETROSPECTIVE FEATURES OF THE TORONTO MEETING. PMID- 17742146 TI - AN ANECDOTE CONCERNING DR. FIELD. PMID- 17742147 TI - THE EGG-LAYING HABITS OF MEGARHYSSA (THALESSA). PMID- 17742148 TI - A CONDENSATION PUMP. PMID- 17742149 TI - THE AMERICAN CHEMICAL SOCIETY. PMID- 17742151 TI - CRUISE OF THE ALBATROSS. PMID- 17742150 TI - THE CENTURY'S PROGRESS IN APPLIED MATHEMATICS. PMID- 17742152 TI - THE TWELFTH ANNUAL MEETING OF THE GEOLOGICAL SOCIETY OF AMERICA. PMID- 17742153 TI - SCIENTIFIC JOURNMALS AND ARTICLES. PMID- 17742154 TI - HOMOLOGIES OF THE WING VEINS OF HYMENOPTERA. PMID- 17742155 TI - NOTES ON INORGANIC CHEMISTRY. PMID- 17742156 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17742157 TI - RECENT ZOOPALEONTOLOGY. PMID- 17742159 TI - Government Support of Research. PMID- 17742158 TI - AGRICULTURAL EXPERIMENT STATIONS. PMID- 17742160 TI - Low-Energy Electron Diffraction: Improved experimental methods provide new information on the structure of surfaces of solids. AB - This discussion of a few preliminary experiments with nickel points out some of the potential uses of low energy electron diffraction in improving our understanding of many types of surface phenomena. The first, and probably the most basic use, is in the study of clean surfaces. As illustrated in this article, the physical properties of the surface layer of atoms may be totally unlike those in the bulk of the crystal. It is necessary to understand such phenomena before a thorough understanding of chemical effects on surfaces can be achieved. The adsorption of gases, oxidation and corrosion, and the formation of epitaxial layers can all be studied in great detail by low energy electron diffraction. PMID- 17742161 TI - Measuring Plasma Density of the Magnetosphere: Electron-density and temperature profiles are measured by the incoherent-scatter technique of radar. PMID- 17742162 TI - Fellowship Expansion: Presidential Plan Criticized at Hearing before House Science, Space Committee. PMID- 17742163 TI - AIBS: Emergency Meeting of Board Produces Steps Designed to Promote Financial Solvency and Confidence. PMID- 17742164 TI - Radio Astronomy: TV's Rush for UHF Threatens Use of Channel. PMID- 17742165 TI - Budget: $14.9 Billion Asked for Research in Fiscal 1964. PMID- 17742166 TI - Status of the Pleistocene Wisconsin Stage in Central North America. AB - A brief review of the history of the Wisconsin Stage in Pleistocene stratigraphy and of research since 1950 shows that post-Sangoman glacial drift older than the Wisconsin drift reported in the older literature is present in central North America. Known and possible stratigraphic positions of the relevant units are shown. PMID- 17742167 TI - Fractionation of Sulfur and Carbon Isotopes in a Meromictic Lake. AB - In the permanently stagnant depths of Green Lake (near Syracuse, N.Y.), sulfide made by bacteria is depleted in heavy sulfur (S(34)), and sulfate is enriched. The fractionation factor, 1.0575, is the greatest yet observed. Isotopic resemblance to salt-dome sulfur deposits is evident, and, like saltdome calcite, the lake's carbon dioxide is depleted in heavy carbon (C(13)). PMID- 17742169 TI - Hymenoptera: Pure Venom from Bees, Wasps, and Hornets. AB - Pure venom can be obtained from bees, wasps, and hornets by electrical stimulation with inexpensive apparatus. PMID- 17742168 TI - Bonding in Xenon Fluorides and Halogen Fluorides. AB - The bonding in rare gas fluorides is similar to that in halogen polyfluorides, and the stability of such compounds should depend primarily on the ionization potential of the central atom. This theory is consistent with findings for all known compounds of the system and yields predictions concerning other systems. PMID- 17742170 TI - SCIENCE NEWS. PMID- 17742171 TI - ATOMIC HYDROGEN AS AN AID TO INDUSTRIAL RESEARCH. PMID- 17742172 TI - JAMES CAMPBELL TODD. PMID- 17742173 TI - THE ICHNOLOGY OF TEXAS. PMID- 17742174 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17742176 TI - DISCOVERY OF FOSSIL TRACKS ON THE NORTH RIM OF THE GRAND CANYON. PMID- 17742175 TI - A CORM ROT OF GLADIOLUS CAUSED BY A PENICILLIUM. PMID- 17742177 TI - ARE SALT SOLUTIONS MUSICAL? PMID- 17742178 TI - UNDULANT FEVER IN AMERICA. PMID- 17742179 TI - ON THE VELOCITY OF SOUND. PMID- 17742180 TI - BANANA STOWAWAYS. PMID- 17742182 TI - ON THE DISTRIBUTION OF CRITICAL TEMPERATURES FOR SPAWNING AND FOR CILIARY ACTIVITY IN BIVALVE MOLLUSCS. PMID- 17742181 TI - AMERICAN SCHOOL OF PREHISTORIC RESEARCH. AB - Of the eleven students taking part, about half were unable to remain for the entire term; these were permitted to join for short periods. In addition to the student body, permission was granted thirty-four other persons interested in our work to take part in our program-especially in Brittany and the Dordogne. Of the fifty conferences given, twenty were by the director and thirty by twenty-eight specialists. To the latter, the director desires to express his deep sense of appreciation. Sixty-three important prehistoric sites and thirty-five museums and special collections were examined. As a result of the twentyfive days of digging, collections were sent to seven contributing institutions. At the end of the season five students remained in the Old World for further study and field work. PMID- 17742183 TI - STARVATION KETOSIS OF THE PRIMATES. PMID- 17742184 TI - Harlow Shapley: President of AAAS, 1947. PMID- 17742186 TI - The International Congress for Applied Mechanics: Paris, September 22-29, 1946. PMID- 17742185 TI - Anesthesia's Second Power: Probing the Mind. PMID- 17742187 TI - The Organization of Arthropod Cuticle: A Modified Interpretation. PMID- 17742188 TI - COMMENTS by Readers. PMID- 17742189 TI - Visibility of the Deer Fly in Flight. PMID- 17742190 TI - Synthetic Caffeine. PMID- 17742191 TI - Production of Yellow Bean Mosaic in Beans by Virus From Mottled Gladiolus. PMID- 17742192 TI - Production and Treatment of Hepatitis With Focal Necrosis of the Liver in White Mice. PMID- 17742193 TI - Forty-Five Years of Continuous Cropping With Lima Beans. PMID- 17742195 TI - Therapy of Experimental Tsutsugamushi Disease (Scrub Typhus). PMID- 17742194 TI - Role of the Axis Cylinder in Transport of Tetanus Toxin. PMID- 17742196 TI - Insecticidal Action of 1-Trichloro-2,2-Bis-(p-Bromophenyl) Ethane (Colorado 9). PMID- 17742197 TI - Lesions of the Pancreatic Islets Produced in Cats by Administration of Glucose. AB - Hydropic degeneration of the islands of Langerhans and permanent severe diabetes mellitus have followed the prolonged injection of intraperitoneal glucose-saline solution in normal as well as in partially depancreatized cats. Positive results were associated with prolonged hyperglycemia. These findings add further evidence in support of the hypothesis that a sustained elevation of blood glucose may, under certain conditions, lead to the production of damage to the islands of Langerhans in this species. Besides hyperglycemia, other disturbances which might be responsible wholly or in part for the island lesions are under study. PMID- 17742198 TI - Studies on the Stability of Streptomycin in Solution. AB - Streptomycin held in solution in concentrations of 100 and 1,000 microg./ml. at 10 degrees C. is stable at pH 6.0, 7.0, and 8.0 for a period of three months. The depressor effect observed in the turbidimetric assay appears to be the result of two factors, buffer salt concentration and pH, and is most marked at pH 6.0. Almost normal activity reappears at pH 8.0 even in the presence of the greater concentration of phosphates. PMID- 17742199 TI - A Technique for Aeration of Sterile Liquid Culture Medium. PMID- 17742200 TI - A New Type of Electroencephalographic Electrode Coordinator With Semipermanent Electrodes. PMID- 17742201 TI - Briquettes With Labels. PMID- 17742202 TI - Ultraviolet Radiation as a Means of Sterilizing Tissue Culture Materials. PMID- 17742203 TI - The Production of Phenocopies in Drosophila Using Visible Light and a Photodynamic Dye. PMID- 17742204 TI - A Qualitative Test for Penicillin. PMID- 17742205 TI - This Week in SCIENCE. PMID- 17742206 TI - Plugging the pipeline. PMID- 17742207 TI - Supporting life on Earth. PMID- 17742208 TI - Ecological economics. PMID- 17742210 TI - Sciencescope. PMID- 17742209 TI - Response. PMID- 17742211 TI - High Noon for Europe's Space Plans. PMID- 17742213 TI - They'd Rather Switch Than Fight. PMID- 17742212 TI - European Researchers Take Pot Shots at ESA's Budget. PMID- 17742215 TI - OTA Endorses the Rhythm Method. PMID- 17742214 TI - Windfall for meta-analysis. PMID- 17742216 TI - Gene therapy trials on the move. PMID- 17742217 TI - Nobel knock-off. PMID- 17742218 TI - Correction. AB - In a list of the world's 10 most-cited scientists (Science, 4 October, p. 28), the name of biologist Robert Tjian was spelled wrong, and his institution was misidentified. Tjian is a Howard Hughes Medical Institute investigator at the University of California at Berkeley. We regret the errors. PMID- 17742219 TI - The ex-commies are coming. PMID- 17742220 TI - Antarctic ozone hole hits record depth. PMID- 17742221 TI - Living thin and long. PMID- 17742222 TI - Galileo's Frustrating Asteroid Pursuit. PMID- 17742224 TI - Relatedness, sex ratios, and controls. PMID- 17742223 TI - Concocting a cosmic recipe for matter. PMID- 17742225 TI - Quantum mechanical calculations to chemical accuracy. AB - Full configuraton-interaction (FCI) calculations have given an unambiguous standard by which the accuracy of theoretical approaches of incorporating electron correlation into molecular structure calculations can be judged. In addition, improvements in vectorization of programs, computer technology, and algorithms now permit a systematic study of the convergence of the atomic orbital (or so-called one-particle) basis set. These advances are discussed and some examples of the solution of chemical problems by quantum mechanical calculations are given to illustrate the accuracy of current techniques. PMID- 17742226 TI - Rapid formation of ontong java plateau by aptian mantle plume volcanism. AB - The timing of flood basalt volcanism associated with formation of the Ontong Java Plateau (OJP) is estimated from paleomagnetic and paleontologic data. Much of OJP formed rapidly in less than 3 million years during the early Aptian, at the beginning of the Cretaceous Normal Polarity Superchron. Crustal emplacement rates are inferred to have been several times those of the Deccan Traps. These estimates are consistent with an origin of the OJP by impingement at the base of the oceanic lithosphere by the head of a large mantle plume. Formation of the OJP may have led to a rise in sea level that induced global oceanic anoxia. Carbon dioxide emissions likely contributed to the mid-Cretaceous greenhouse climate but did not provoke major biologic extinctions. PMID- 17742227 TI - Oxygen isotope zoning in garnet. AB - Oxygen isotope zoning was examined within garnet with the use of the stable isotope laser probe. Four metamorphic garnets from the regional metamorphic terrane in Vermont and the skarn deposit at Carr Fork, Utah, were examined and were found to be concentrically zoned in delta(18)O values. The largest variations in delta(18)O values were observed in the regional metamorphic garnets, where delta(18)O values change by 3 per mil from core to rim. These oxygen isotope zoning profiles reflect the changes in the delta(18)O values of the rocks during garnet growth, which are caused by infiltration of fluids and by dehydration reactions during metamorphism. PMID- 17742228 TI - Visual Observations of the Amorphous-Amorphous Transition in H2O Under Pressure. AB - The vapor-deposited low-density amorphous phase of H(2)O was directly compressed at 77 kelvin with a diamond-anvil cell, and the boundary between the low-density amorphous phase and the high-density amorphous phase was observed while the sample was warmed under compression. The transition from the low-density amorphous phase to the high-density amorphous phase was distinct and reversible in an apparently narrow pressure range at approximately 130 to approximately 150 kelvin, which provided experimental evidence for polymorphism in amorphous H(2)O. PMID- 17742229 TI - The structure of the c60 molecule: x-ray crystal structure determination of a twin at 110 k. AB - Single-crystal x-ray diffraction methods were used to determine the crystal and molecular structure of C(60) buckminsterfullerene. At 110 kelvin C(60) is cubic, apparent Laue symmetry m3m, but it exhibits noncrystallographic systematic extinctions indicative of a twin in which I(hkl) and I(khl) are superimposed. In fact, C(60) crystallizes with four molecules in space group [See equation in the PDF file] of the cubic system (Laue symmetry m3) with lattice constant a = 14.052(5) angstroms (A) at 110 kelvin. The twin components are equal. A given component, which has crystallographically imposed symmetry [See equation in the PDF file] displays an ordered structure of a truncated icosahedron. The five independent C=C bonds that join C(6) rings average 1.355(9) A; the ten independent C-C bonds that join C(6) and C(5) rings average 1.467(21) A. The mean atom-to-atom diameter of the C(60) molecule is 7.065(3) A. The molecules are very tightly packed in the crystal structure, with intermolecular C...C distances as short as 3.131(7) A. PMID- 17742230 TI - Bond lengths in free molecules of buckminsterfullerene, c60, from gas-phase electron diffraction. AB - Electron diffraction patterns of the fullerene C(60) in the gaseous state have been obtained by volatilizing it from a newly designed oven-nozzle at 730 degrees C. The many peaks of the experimental radial distribution curve calculated from the scattered intensity are completely consistent with icosahedral symmetry for the free molecule. On the basis of this symmetry assumption, least-squares refinement of a model incorporating all possible interatomic distances led to the values r(g)(C(1)-C(2)) = 1.458(6) angstroms (A) for the thermal average bond length within the five-member ring (that is, for the bond fusing five- and six member rings) and r(g)(C(1)-C(6)) = 1.401(10) A for that connecting five-member rings (the bond fusing six-member rings). The weighted average of the two bond lengths and the difference between them are the values 1.439(2) A and 0.057(6) A, respectively. The diameter of the icosahedral sphere is 7.113(10) A. The uncertainties in parentheses are estimated 2sigma values. PMID- 17742231 TI - Haplodiploidy and the evolution of facultative sex ratios in a primitively eusocial bee. AB - In eusocial Hymenoptera, the haplodiploid system of sex determination creates relatedness asymmetries such that workers are more closely related on average to their sisters than to their brothers. For such societies, kin-selection theory and sex-ratio theory predict that workers maximize their inclusive fitness by biasing the investment sex ratio toward females. To test the prediction of sex ratio biasing, relatedness asymmetries were experimentally manipulated in colonies of the primitively eusocial bee Augochlorella striata (Halictidae: Hymenoptera) by removing or not removing foundress queens. Queenright colonies (relatedness asymmetry present) produced a more female-biased sex ratio than did queenless colonies (relatedness asymmetry absent). Worker reproduction and unmated replacement queens can be discounted as alternative explanations. Workers therefore facultatively adjusted their colony's sex ratio and, in the presence of a relatedness asymmetry, biased the investment sex ratio toward their more closely related sisters and away from their more distantly related brothers. PMID- 17742232 TI - Continuing exclusions. PMID- 17742233 TI - What children know. PMID- 17742235 TI - Tide-gauge records. PMID- 17742236 TI - Products & materials. PMID- 17742234 TI - Evolution and physiology. PMID- 17742237 TI - THE ORGANIZATION OF KNOWLEDGE. PMID- 17742238 TI - THE FIFTH YEAR OF THE TROPICAL RESEARCH STATION. PMID- 17742239 TI - GRANTS FOR RESEARCH MADE BY THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17742240 TI - PRACTICABLE SUBSTITUTES FOR GRAIN ALCOHOL. PMID- 17742241 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17742243 TI - NOTES ON WOODS. PMID- 17742244 TI - GENETICS OF THE VIENNA WHITE RABBIT. PMID- 17742242 TI - IRIDESCENT CLOUDS. PMID- 17742245 TI - THE AMERICAN SOCIETY OF AGRONOMY. PMID- 17742246 TI - Weathered Bedrock in New Jersey. PMID- 17742247 TI - A Thinking Man's Movie? PMID- 17742249 TI - Science in the News. PMID- 17742248 TI - Gilbert Morgan Smith, Botanist. PMID- 17742250 TI - Evidence That Cut Optic Nerve Fibers in a Frog Regenerate to Their Proper Places in the Tectum. AB - The frog's retina projects into the superficial neuropil of the opposite tectum in four functionally different layers of terminals. Each layer displays a continuous map of the retina in terms of its particular function. The four maps are in register. The fourth-dimensional order is reconstituted after section and regeneration of the optic fibers. PMID- 17742251 TI - Lunar and Solar Perturbations on Satellite Orbits. AB - Calculations of the solar and lunar effects on highly eccentric satellite orbits show that the sun and the moon may cause large changes in perigee height over extended periods of time. The amplitude and sign of the perigee height variations depend on the orbit parameters and the hour of launch; for a typical orbit and various choices of launch time, the perigee height will either rise or fall at the rate of 1 km/day over the course of several months. These results may be significant in deciding the launch conditions for future satellites with highly eccentric orbits. PMID- 17742253 TI - Weathered Bedrock in New Jersey. PMID- 17742255 TI - Bees are easily distracted. PMID- 17742254 TI - Oceanography: an international laboratory. PMID- 17742256 TI - Intellectual loneliness. PMID- 17742257 TI - Letters to the editor. PMID- 17742259 TI - Starvation: weapon of warfare. PMID- 17742258 TI - Pyrotechnics. PMID- 17742261 TI - A magnetic model of matter. PMID- 17742260 TI - For full technological assessment. PMID- 17742262 TI - Science and society in equilibrium. PMID- 17742263 TI - Earthquakes and nuclear tests: playing the odds on amchitka. PMID- 17742265 TI - Trouble at NASA: Space Scientists Resign. PMID- 17742266 TI - Senate Imposes CBW Limitations, Cuts Defense Research. PMID- 17742267 TI - Mariner 7 television pictures: first report. PMID- 17742268 TI - Glacial age marsh, lafayette park, washington, d.C. AB - Organic sediments beneath historic Lafayette Park mark the site of a freshwater marsh which bordered the Potomac River when it was 15 meters above its present level. Plant microfossils and ice-rafted boulders indicate a climate much colder than now. The carbon-14 age of more than 45,000 years and palynological studies suggest an early Wisconsin age. PMID- 17742269 TI - Venus: mapping the surface reflectivity by radar interferometry. AB - The surface reflectivity of Venus obtained by radar interferometry at a wavelength of 3.8 centimeters has been mapped for a region extending approximately from -80 degrees to 0 degrees in longitude (Carpenter's definition) and from -50 degrees to +40 degrees in latitude. The map is free from the twofold range-Doppler ambiguity because the interferometer fringe pattern makes possible the separation of two points of equal range and Doppler shift. The map presents many new features and clearly delineates features already observed. Most notably, the map shows large circular regions of significantly lower reflectivity than their surroundinigs. PMID- 17742270 TI - Carbonado: natural polycrystalline diamond. AB - Carbonados are porous aggregates of mostly xenomorphic diamond crystallites ranging in diameter from a fraction of a micron to over 20 microns. Crystalline inclusions (up to 3 percent) occur in the pores of the crystallites and consist mainly of orthoclase and small amounts of other igneous, metamorphic, and secondary minerals. PMID- 17742271 TI - Microphotometric determination of preferred orientation in undeformed dolomites. AB - Preferred orientation was observed in certain undeformed dolomites with a microphotometric technique. The preferred direction of the c-axis was found to be perpendicular to the bedding planes. The degree of orientation is rather slight, but is considered significant due to the fact that thousands of crystals are included in each measurement. It is suggested that the preferred orientation was acquired during an early diagenetic stage of dolomitization, when the individual crystals could rotate and adjust their position so that their maximum cross section tended to lie horizontally. PMID- 17742272 TI - Orientation of the dipole moments of hydroxyl groups in oxidized and unoxidized biotite. AB - Observations of the infrared absorption bands attributed to the stretching vibrations of hydroxyl groups in biotite containing predominantly ferrous iron show that the dipole moments of the hydroxyls associated with ferrous iron are oriented perpendicular to the cleavage plane of the lattice. Oxidation in the biotite from ferrous iron to ferric iron results in the disappearance of the infrared absorption bands due to the hydroxyls associated with ferrous iron. The dipole moments of the hydroxyls associated with ferric iron in the oxidized biotite have been shown to be in an inclined position with respect to the cleavage plae. Our experiments confirm the hypothesis of Barshad and Kishk regarding the effect of oxidation on the replaceability of interlayer potassium ions in biotite by ammonium ions. PMID- 17742273 TI - Statistics of unseen animals. PMID- 17742274 TI - SCIENCE NEWS. PMID- 17742275 TI - THE SYMMETRY OF TIME IN PHYSICS. PMID- 17742277 TI - CAN A CATFISH COUNT? PMID- 17742276 TI - HOW OLD IS THE PLEISTOCENE? PMID- 17742278 TI - INACTIVITY OF CHICORY. PMID- 17742279 TI - THE FUTURE OF TAXONOMY. PMID- 17742280 TI - A CONVENIENT AID IN BALANCING CENTRIFUGE TUBES. PMID- 17742281 TI - RECORDING CEREBRAL ACTION CURRENTS. PMID- 17742282 TI - THE REGULAR SPRING MEETING OF THE EXECUTIVE COMMITTEE. PMID- 17742283 TI - THE STRUCTURE OF GLUTATHIONE. PMID- 17742284 TI - TRANSMISSION CHANGES IN ULTRAVIOLET GLASSES DURING HIGH TEMPERATURE EXPOSURE TO LIGHT. PMID- 17742285 TI - SCIENCE NEWS. PMID- 17742287 TI - OUR DEBT TO FARADAY'S EPOCH. PMID- 17742286 TI - HOW THE OTHER HALF LIVE. PMID- 17742288 TI - OBITUARY. PMID- 17742289 TI - THE PROCESS OF GIORDANO BRUNO. PMID- 17742291 TI - RELATIONS BETWEEN FUNDAMENTAL PHYSICAL CONSTANTS. PMID- 17742290 TI - A SMALL INSECT WHICH STINGS SEVERELY. PMID- 17742292 TI - HAMIVOROUS FISH. PMID- 17742294 TI - MULTIPLE LABORATORY INCUBATOR FOR THE BIOLOGICAL STUDY OF CHICK EMBRYO. PMID- 17742293 TI - A ROTARY MYOGRAPH. PMID- 17742295 TI - ON THE LAWS OF KINETIC SYSTEMS. PMID- 17742297 TI - HENRY AUGUSTUS ROWLAND. PMID- 17742296 TI - RATE OF SEA CLIFF RECESSION ON THE PROPERTY OF THE SCRIPPS INSTITUTION OF OCEANOGRAPHY AT LA JOLLA, CALIFORNIA. PMID- 17742298 TI - IMMUNITY AND PROTECTIVE INOCULATION. PMID- 17742300 TI - LEGISLATIVE RECOGNITION OF SCIENTIFIC WORK. PMID- 17742299 TI - AN ELECTROCHEMICAL LABORATORY AT THE UNIVERSITY OF PENNSYLVANIA. PMID- 17742301 TI - SPRING MEETING OF THE COUNCIL OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17742303 TI - THE PROPER NAME OF THE ALPINE CHOUGH. PMID- 17742302 TI - PRIORITY OF PLACE AND THE METHOD OF TYPES. PMID- 17742304 TI - BOTANICAL NOTES. PMID- 17742305 TI - IS THE EIGHT-HOUR WORKING-DAY RATIONAL? PMID- 17742306 TI - THE CARE OF PAMPHLET COLLECTIONS. PMID- 17742307 TI - PROGRAM OF THE YALE CHAPTER OF SIGMA XI FOR 1916-1917. PMID- 17742308 TI - THE BRAIN COLLECTION OF THE U. S. NATIONAL MUSEUM. PMID- 17742309 TI - THE ENDOWMENT OF A MEDICAL SCHOOL AT THE UNIVERSITY OF CHICAGO. PMID- 17742310 TI - THE COUNCIL OF NATIONAL DEFENCE. PMID- 17742311 TI - CAN A BODY EXERT A FORCE UPON ITSELF? PMID- 17742312 TI - A COMMON, BUT INCORRECT, STATEMENT CONCERNING THE NUMBER OF BACTERIA IN MILK. PMID- 17742313 TI - LATERAL VISION AND ORIENTATION. PMID- 17742314 TI - OSTWALD'S HANDBOOK OF COLLOIDAL CHEMISTRY. PMID- 17742315 TI - THE RELATION OF OSMOTIC PRESSURE AND IMBIBITION IN LIVING CELLS. PMID- 17742316 TI - THE RESULTS OF EXTIRPATION OF THE ANTERIOR LOBE OF THE HYPOPHYSIS AND OF THE THYROID OF RANA PIPIENS LARVAe. PMID- 17742317 TI - MICROTECHNICAL METHODS FOR STUDYING CERTAIN PLANT-SUCKING INSECTS IN SITU. PMID- 17742318 TI - THE ECOLOGICAL SOCIETY OF AMERICA. PMID- 17742319 TI - ECOLOGY: Conservation Targets: Do They Help? AB - No more than 5% of the land area worldwide is being set aside for the protection of nature, and there is little evidence that much tropical biodiversity will survive outside of well-managed reserves. Many international development and conservation organizations recommend that at least 10% of territory be protected, though ecologists generally concur that at least 50% of all species will soon be lost if 90% of the habitat is seriously disrupted. Current policies, therefore, are a prescription for a massive loss of biodiversity. PMID- 17742320 TI - MODERN-LANGUAGE ASSOCIATION. PMID- 17742321 TI - SCARLET-FEVER REPORT.--III. PMID- 17742322 TI - MENTAL SCIENCE. PMID- 17742323 TI - EXPLORATION AND TRAVEL. PMID- 17742324 TI - Is there a Venomous Lizard (Heloderma)? PMID- 17742325 TI - Children's Development. PMID- 17742326 TI - The Trinity Formation of Arkansas, Indian Territory, and Texas. PMID- 17742327 TI - Weather-Predicting. PMID- 17742328 TI - Sections of Fossils. PMID- 17742329 TI - American Microscopes. PMID- 17742330 TI - Queries. PMID- 17742331 TI - The Eskimo Rmig-Finger. PMID- 17742332 TI - Cheyenne. PMID- 17742334 TI - ADDRESS OF MAJOR POWELL IN MEMORY OF PROFESSOR BAIRD. PMID- 17742333 TI - Arkansaw and Kansaw. PMID- 17742335 TI - National Goals for Education. PMID- 17742337 TI - News of Science. PMID- 17742336 TI - Cenozoic History of the Bering Land Bridge: The seaway between the Pacific and Arctic basins has often been a land route between Siberia and Alaska. PMID- 17742339 TI - Mating for "Hybrid Vigor". PMID- 17742340 TI - Science in Israel. PMID- 17742341 TI - Using Theses for Scientific Communication. PMID- 17742342 TI - Biological Bromination. PMID- 17742344 TI - "Feedback" in Evolution. PMID- 17742343 TI - Biological Bromination. PMID- 17742345 TI - "Feedback" in Evolution. PMID- 17742346 TI - U. S. Research Abroad. PMID- 17742348 TI - Plants and Animals: Vive la Difference. PMID- 17742347 TI - Public Understanding. PMID- 17742349 TI - Indian Ocean Expedition. PMID- 17742350 TI - Photocopying and the Journals. PMID- 17742351 TI - Partnership. PMID- 17742352 TI - Emotional Perils for All. PMID- 17742353 TI - Translation of Russian Journals. PMID- 17742354 TI - No Antineoplastic Effect. PMID- 17742355 TI - Hoax Protested. PMID- 17742356 TI - Barriers to Innovation. PMID- 17742357 TI - The Close-Packed-Spheron Theory and Nuclear Fission. PMID- 17742358 TI - Rules for Referees. PMID- 17742359 TI - Earthquake Prediction: OST Panel Recommends 10-Year Program. PMID- 17742360 TI - New Health Act: AMA Criticism Reflected in Adoption of Bill on Heart, Cancer, and Stroke. PMID- 17742361 TI - Microorganisms from the Late Precambrian of Central Australia. AB - An assemblage of structurally and organically well preserved microorganisms, interpreted as both green and blue-green algae, has been found in chert facies of the Bitter Springs limestone from the upper Precambrian of central Australia. This appears to be the earliest known occurrence of green algae in the fossil record. These organisms are among the oldest known multicellular and unicellular fossils exhibiting distinct histological preservation. PMID- 17742363 TI - Macroglobulin-Producing Plasma-Cell Tumor in Mice: Identification of a New Light Chain. AB - A transplantable plasmacell tumor in mice produces both a gammaM-macroglobulin serum protein with a sedimentation coefficient of 17S and a kappa-type urinary protein. The reduced and alkylated macroglobulin, when examined by electrophoresis in acid-urea polyacrylamide gel, had a fast component which migrated in the same position as the urinary protein and also a slow component. These two components, as shown by exclusion chromatography, represent the light and heavy polypeptide chains of the gammaM-macroglobulin. The aforementioned macroglobulin was antigenically related to that in normal mouse serum. PMID- 17742362 TI - Hydrogen Emission Line n110 rarr n109: Detection at 5009 Megahertz in Galactic H II Regions. AB - The hydrogen emission line n(1l0) --> n(109) at the frequency 5009 megahertz which was predicted by Kardashev has been detected in M 17, Orion, and nine other galactic H II regions with the 42.7-m (140-foot) telescope and a 20-channel receiver at the National Radio Astronomy Observatory. The measured product of the half-power width of the line times the ratio of line-to-continuum brightness temperature is larger than that predicted by Kardashev's theory. The radial velocity obtained for M 17 and Orion agrees well with optical measurements. The search for a similar line of excited helium was without success. PMID- 17742365 TI - Luminescence Dosimetry. PMID- 17742364 TI - National Academy of Sciences. PMID- 17742366 TI - Forthcoming Events. PMID- 17742367 TI - SCIENCE NEWS. PMID- 17742368 TI - CYCLIC AND NON-CYCLIC ASPECTS OF EROSION. PMID- 17742369 TI - THE NATIONAL MAPPING PLAN OF THE NATIONAL RESOURCES BOARD. PMID- 17742371 TI - DEATH OF THE OLDEST CHIMPANZEE IN CAPTIVITY. PMID- 17742370 TI - SOME ZOOGEOGRAPHICAL PROBLEMS OF THE NORTHERN PACIFIC. PMID- 17742372 TI - SOCIAL BEHAVIOR OF THE NORMAL AND CASTRATED LIZARD, ANOLIS CAROLINENSIS. PMID- 17742374 TI - BREEDING RUST-RESISTANT SPRING WHEATS. PMID- 17742373 TI - SELENIUM IN NATIVE RANGE PLANTS OCCURRING ON SOILS DERIVED FROM PERMIAN OR TRIASSIC (?) SEDIMENTS. PMID- 17742375 TI - EFFECT OF CYSTINE DISULFOXIDE ON SPONTANEOUS TUMORS OF THE MOUSE. PMID- 17742378 TI - THE EVOLUTION OF THE SCIENTIFIC INVESTIGATOR. PMID- 17742376 TI - AN EASILY CONSTRUCTED RELAY. PMID- 17742377 TI - HOLLOW-GROUND SLIDES FOR WHOLE MOUNTS MADE WITH THE DENTAL ENGINE. PMID- 17742379 TI - THE EVIDENCE OF EVOLUTION. PMID- 17742380 TI - ON CITING THE TYPES OF NEW GENERA. PMID- 17742381 TI - INTRUSIVE BURIALS IN ANCIENT MOUNDS. PMID- 17742382 TI - VARIAe AUCTORITATIS. PMID- 17742383 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17742384 TI - THE NATIONAL ANTARCTIC EXPEDITION. PMID- 17742385 TI - THE CROCKER ECLIPSE EXPEDITION OF THE LICK OBSERVATORY. PMID- 17742386 TI - Nuclear Ships. PMID- 17742388 TI - New Approach To Teaching Intermediate Mathematics: It is based on a resolution of the spectra of meanings of the letter x and the term variable. PMID- 17742387 TI - High Atmosphere Densities: To explain satellite observations, models of the thermosphere must allow for diffusion and other factors. PMID- 17742389 TI - A Human Enterprise: Science as lived by its practitioners bears but little resemblance to science as described in print. PMID- 17742390 TI - News of Science. PMID- 17742391 TI - Preliminary Note on Kimzeyite, a New Zirconium Garnet. PMID- 17742393 TI - The Responsibilities of Biologists. PMID- 17742394 TI - The Responsibilities of Biologists. PMID- 17742395 TI - Science on TV. PMID- 17742396 TI - How Shall We Pay for Research and Education? PMID- 17742397 TI - News of Science. PMID- 17742398 TI - Provincial Universities in the United Kingdom. AB - In the article "Provincial universities in the United Kingdom," by Trevor I. Williams [Science 124, 347 (24 Aug. 1956)], the names of the people identified in the picture on the left-hand side of page 348 were misspelled. The correct names are M. K. Das Gupta and R. C. Jennisson. PMID- 17742399 TI - Occurrence of a Bitter Principle in Carrots. PMID- 17742400 TI - Miscellaneous Publications. PMID- 17742402 TI - Meetings and Societies. PMID- 17742403 TI - EQUIPMENT NEWS. PMID- 17742405 TI - WILDIERS' BIOS. PMID- 17742404 TI - SCIENCE NEWS. PMID- 17742407 TI - THE AMERICAN MUSEUM OF NATURAL HISTORY. PMID- 17742406 TI - SOME FORCES IN MAN'S SOCIAL EVOLUTION. PMID- 17742408 TI - MARY A. DAY. PMID- 17742410 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17742409 TI - "SOOT" IN COAL. PMID- 17742411 TI - NITROGEN LOSSES FROM COMPOSTS. PMID- 17742412 TI - WEAK LEGS IN CHICKENS. PMID- 17742413 TI - OBSERVATIONS ON TAXONOMIC FACTORS USED IN THE GENUS CERCOSPORA. PMID- 17742414 TI - INDICATOR REACTION AS A SOURCE OF ERROR IN pH DETERMINATIONS. PMID- 17742415 TI - THE AMERICAN MATHEMATICAL SOCIETY. PMID- 17742416 TI - A GEOMETRIC BASIS FOR PHYSICAL AND ORGANIC PHENOMENA. PMID- 17742417 TI - ERRONEOUS GENERIC DETERMINATIONS OF BEES. PMID- 17742419 TI - THE CANONS OF COMPARATIVE ANATOMY. PMID- 17742420 TI - HYGROMETRY IN TERMS OF THE WEIGHT OF A FILM OF GELATINE. PMID- 17742418 TI - THE NECESSITY FOR BETTER BOOK AND NEWSPAPER MANUFACTURE WITH RESPECT TO MATERIALS USED. PMID- 17742421 TI - SOME ANALYSIS OF THE URINE OF REPTILES. PMID- 17742422 TI - ADDRESS BEFORE THE SECTION OF MATHEMATICS AND PHYSICS. PMID- 17742423 TI - SPECIAL MEETING, ITHACA, NEW YORK, JUNE 28-JULY 3, 1906. SECTION E--GEOLOGY AND GEOGRAPHY. PMID- 17742424 TI - WHEN DID FRANKLIN INVENT TIlE LIGHTNING-ROD? PMID- 17742425 TI - DRIED COTTON CULTURES ONCE MORE. PMID- 17742426 TI - GEOLOGY OF SOUTH BRAZIL. PMID- 17742427 TI - THE FOREST DISTRICTS OF UGANDA. PMID- 17742428 TI - APPOINTMENTS AND REMOVALS AT STANFORD UNIVERSITY. PMID- 17742430 TI - Quaternary Volcanic Ash in Southern Alberta, Canada. PMID- 17742429 TI - Physics of the Atmosphere. PMID- 17742431 TI - BEFORE AND AFTER LISTER. PMID- 17742433 TI - THE UNIVERSITY OF MINNESOTA AND THE MAYO FOUNDATION. PMID- 17742432 TI - LADY HUGGINS. PMID- 17742434 TI - CONDITIONS AT THE UNIVERSITY OF UTAH. PMID- 17742435 TI - THE PACIFIC DIVISION OF THE AMERICAN ASSOCIATION. PMID- 17742436 TI - COMPLEXITY OF THE ALEXANDRLIA SERIES. PMID- 17742437 TI - EYE SHADES FOR MICROSCOPICAL WORK. PMID- 17742439 TI - ALABAMA ARGILLACEA IN MINNESOTA. PMID- 17742438 TI - CHEMIHYDROMETRY. PMID- 17742440 TI - THE PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (NUMBERS 1-4). PMID- 17742441 TI - A MODIFICATION OF THE BELLANI POROUS PLATE ATMOMETER. PMID- 17742442 TI - THE EFFECT OF TEMPERATURE ON THE LIFE CYCLE OF MUSCA DOMESTICA AND CULEX PIPIENS. PMID- 17742443 TI - SCIENCE NEWS. PMID- 17742444 TI - THE PERMANENT SECRETARY'S REPORT ON THE CINCINNATI MEETING. PMID- 17742445 TI - LEGISLATIVE AND EXECUTIVE PROCEEDINGS AT CINCINNATI. PMID- 17742446 TI - THE COUNCIL ROLL AT CINCINNATI. PMID- 17742447 TI - OFFICERS ELECTED. PMID- 17742448 TI - THE PRESIDENT: A biographical note. PMID- 17742449 TI - THE CINCINNATI SESSIONS OF THE SECTIONS AND SOCIETIES. PMID- 17742450 TI - FINANCIAL REPORTS. PMID- 17742452 TI - SECTION B (PHYSICS). PMID- 17742451 TI - SECTION A (MATHEMATICS). PMID- 17742453 TI - SECTION C (CHEMISTRY). PMID- 17742454 TI - SECTION D (ASTRONOMY). PMID- 17742455 TI - SECTION E (GEOLOGY AND GEOGRAPHY). PMID- 17742456 TI - SECTION F (ZOOLOGICAL SCIENCES). PMID- 17742457 TI - SECTION G (BOTANICAL SCIENCES). PMID- 17742458 TI - THE PHYSIOLOGICAL IMPORTANCE OF PHASE BOUNDARIES. PMID- 17742459 TI - THE PUBLICATION OF THE RESULTS OF INVESTIGATIONS MADE IN EXPERIMENT STATIONS IN TECHNICAL SCIENTIFIC JOURNALS. PMID- 17742460 TI - THE NAVAL CONSULTATION BOARD. PMID- 17742461 TI - POTASSIUM FROM THE SOIL. PMID- 17742462 TI - ELEMENTARY MECHANICS. PMID- 17742464 TI - THE "PAN-AMERICAN SCIENTIFIC CONGRESS". PMID- 17742463 TI - THE END IS NOT YET! PMID- 17742465 TI - HEMOGLOBINOPHILIC BACTERIA. PMID- 17742466 TI - ARTIFICIAL DAYLIGHT FOR THE MICROSCOPE. PMID- 17742467 TI - A NEW ALFALFA LEAF-SPOT IN AMERICA. PMID- 17742468 TI - DIFFERENTIATION OF WANDERING MESENCHYMAL CELLS IN THE LIVING YOLK-SAC. PMID- 17742469 TI - ANTHROPOLOGY AT THE SAN FRANCISCO MEETING. PMID- 17742470 TI - DOCTORATES CONFERRED BY AMERICAN UNIVERSITIES. PMID- 17742471 TI - DURER'S "CONTRIBUTION" TO GESNER'S NATURAL HISTORY. PMID- 17742472 TI - THE UNITED STATES BUREAU OF EDUCATION. PMID- 17742473 TI - TELEGONY AS INDUCED REVERSION. PMID- 17742474 TI - ON THE CONNECTION BETWEEN STIMULATION AND CHANGES IN THE PERMEABILITY OF THE PLASMA MEMBRANES OF THE IRRITABLE ELEMENTS. PMID- 17742475 TI - THE FORTIETH GENERAL MEETING OF THE AMERICAN CHEMICAL SOCIETY. PMID- 17742476 TI - DEDICATION OF THE CHEMISTRY BUILDING OF THE COLLEGE OF THE CITY OF NEW YORK, MAY 14, 1908. PMID- 17742477 TI - THE NATIONAL CONSERVATION COMMISSION. PMID- 17742478 TI - BLACKHEAD, A COCCIDIAL DISEASE OF TURKEYS. PMID- 17742479 TI - THE INLAND WATERWAYS COMMISSION. PMID- 17742480 TI - THE HANOVER MEETING OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17742481 TI - SCIENCE NEWS. PMID- 17742482 TI - THE REVOLT OF THE BIOCHEMISTS. PMID- 17742484 TI - PSYCHIC ANALOGUES OF ALLERGY. PMID- 17742483 TI - CLINICAL INVESTIGATION. PMID- 17742485 TI - CRYSTALLINE AMYLASE. PMID- 17742486 TI - LEAF DIAGNOSIS AND THE INTERPRETATION OF FERTILIZER REQUIREMENTS OF PLANTS. PMID- 17742489 TI - UNITED STATES GEOLOGICAL SURVEY UNPUBLISHED LITHOGRAPHIC PLATES OF VERTEBRATE FOSSILS FOR DISTRIBUTION. PMID- 17742488 TI - THE DIVINING ROD AND FAKERS. PMID- 17742487 TI - THE MECHANISM OF CROSSING-OVER. PMID- 17742490 TI - THE VISIT OF DR. JAKOB E. LANGE. PMID- 17742491 TI - A SIMPLE ULTRA-CENTRIFUGE. PMID- 17742492 TI - A METHOD FOR COMPARING GROWTH RATES BY MEANS OF A PROTRACTOR. PMID- 17742494 TI - CERCOSPORELLA HERPOTRICHOIDES FRON, THE CAUSE OF THE COLUMBIA BASIN FOOTROT OF WINTER WHEAT. PMID- 17742495 TI - THE SEX RATIO AMONG HUMAN STILL-BIRTHS. PMID- 17742493 TI - ON MOLECULAR ORGANIZATION IN AMEBAN PROTOPLASM. PMID- 17742496 TI - SCIENCE NEWS. PMID- 17742497 TI - THE ORIGIN OF LAND PLANTS. PMID- 17742498 TI - RELATIVE LENGTH OF PLEISTOCENE GLACIAL AND INTERGLACIAL STAGES. PMID- 17742499 TI - THE OXYGEN CONSUMPTION OF NERVE DURING ACTIVITY. PMID- 17742500 TI - SETIGEROUS CYSTS IN THE EARTHWORM. PMID- 17742502 TI - THE LUBECK DISASTER. PMID- 17742501 TI - AUTO-TRANSPLANTED GASTRIC POUCH FUNCTIONING FOR FIVE YEARS. PMID- 17742503 TI - INTRA VITAM TECHNIQUE FOR THE STUDY OF THE LIVING CELLS OF INSECTS. PMID- 17742504 TI - A RAPID POSITIVE CONTROL METHOD OF HANDLING SMALL QUANTITIES OF LIQUIDS. PMID- 17742505 TI - EXCESSIVE TAX ON SOIL FERTILITY BY CROP PRODUCTION ON POOR LAND. PMID- 17742506 TI - COMPARATIVE RACIAL DIFFERENCES IN COLOR-BLINDNESS. PMID- 17742507 TI - This week in science. PMID- 17742509 TI - Corrections and clarifications. AB - In the letter of 23 October by Charles A. Gardner (p. 530), Dr. Gardner's address was incorrectly given as the Subcommittee on Human Resources and Intergovernmental Relations of the House Committee on Government Operations. Dr. Gardner was a AAAS Congressional Science Fellow assigned to that subcommittee through August 1992, but the views expressed in his letter were his own and not those of the subcommittee. PMID- 17742508 TI - Superconductivity revisited. PMID- 17742510 TI - NIH Panel OK's Vaccine Test-in a New Form. PMID- 17742512 TI - Science in the transition. PMID- 17742511 TI - Scripps signs a deal with sandoz. PMID- 17742513 TI - Results on planetary name game. PMID- 17742514 TI - How to grow oil in the persian gulf. PMID- 17742515 TI - National metacenter to link supercomputers. PMID- 17742516 TI - Ex-yugoslavian scientists needed. PMID- 17742517 TI - A kinder, gentler chip inspection. PMID- 17742518 TI - Caskey Promises a Democratic HUGO. PMID- 17742519 TI - Having it both ways in the mantle. PMID- 17742520 TI - Quake heightens concern, uncertainty. PMID- 17742522 TI - ;Housekeeping' genes may have biotech applications. PMID- 17742521 TI - Gene Research Flowers in Arabidopsis thallana. PMID- 17742523 TI - Paleoseismology: a search for ancient earthquakes in puget sound. PMID- 17742524 TI - Himalayan tectonics, weathering processes, and the strontium isotope record in marine limestones. AB - The time evolution of the isotopic composition of seawater strontium (the ratio of strontium-87 to strontium-86) over the last 500 million years has the form of an asymmetric trough. The values are highest in the Cambrian and Recent (0.7091) and lowest in the Jurassic (0.7067). Superimposed on this trend are a number of smaller oscillations. Consideration of the geochemical cycle of strontium and the dynamics of weathering shows that only Himalayan-style continental collisions can influence the isotope ratio on the scale observed. The contemporary Himalayan orogeny is by far the largest since the late Precambrian Pan-African event that produced the high in the Cambrian. PMID- 17742526 TI - A tsunami about 1000 years ago in puget sound, washington. AB - Water surged from Puget Sound sometime between 1000 and 1100 years ago, overrunning tidal marshes and mantling them with centimeters of sand. One overrun site is 10 kilometers northwest of downtown Seattle; another is on Whidbey Island, some 30 kilometers farther north. Neither site has been widely mantled with sand at any other time in the past 2000 years. Deposition of the sand coincided-to the year or less-with abrupt, probably tectonic subsidence at the Seattle site and with landsliding into nearby Lake Washington. These findings show that a tsunami was generated in Puget Sound, and they tend to confirm that a large shallow earthquake occurred in the Seattle area about 1000 years ago. PMID- 17742525 TI - Abrupt uplift within the past 1700 years at southern puget sound, washington. AB - Shorelines rose as much as 7 meters along southern Puget Sound and Hood Canal between 500 and 1700 years ago. Evidence for this uplift consists of elevated wave-cut shore platforms near Seattle and emerged, peat-covered tidal flats as much as 60 kilometers to the southwest. The uplift was too rapid for waves to leave intermediate shorelines on even the best preserved platform. The tidal flats also emerged abruptly; they changed into freshwater swamps and meadows without first becoming tidal marshes. Where uplift was greatest, it adjoined an inferred fault that crosses Puget Sound at Seattle and it probably accompanied reverse slip on that fault 1000 to 1100 years ago. The uplift and probable fault slip show that the crust of the North America plate contains potential sources of damaging earthquakes in the Puget Sound region. PMID- 17742527 TI - Paleoearthquakes in the puget sound region recorded in sediments from lake washington, u.s.a. AB - Holocene sediments in Lake Washington contain a series of turbidites that were episodically deposited throughout the lake. The magnetic signatures of these terrigenous layers are temporally and areally correlatable. Large earthquakes appear to have triggered slumping on the steep basin walls and landslides in the drainage area, resulting in turbidite deposition. One prominent turbidite appears to have been deposited about 1100 years ago as the result of a large earthquake. Downcore susceptibility patterns suggest that near-simultaneous slumping occurred in at least three separate locations, two of which now contain submerged forests. Several other large earthquakes may have occurred in the last 3000 years. PMID- 17742528 TI - Prehistoric rock avalanches in the olympic mountains, washington. AB - Rock avalanches blocked streams in the Olympic Mountains southwest of Puget Sound during the past few thousand years. Limiting radiocarbon ages indicated that three or four of six avalanches occurred from 1000 to 1300 years ago or shortly thereafter. Most of the dates were from the outer preserved rings of trees drowned behind avalanche dams. These three or four avalanches may be coeval not only with one another but also with abrupt tectonic deformation in western Washington. No rock avalanches in the Olympic Mountains are known to have resulted from storms or earthquakes during the past century. The avalanches strengthen the case that a large prehistoric earthquake occurred in the Puget Sound region. PMID- 17742529 TI - Tree ring correlation between prehistoric landslides and abrupt tectonic events in Seattle, washington. AB - Radiocarbon ages of submerged trees on landslide deposits in Lake Washington, Seattle, indicate that the most recent slides in three separate areas may have occurred simultaneously about 1000 years ago. Tree ring crossdating shows that seven bark-bearing trees from one of these recent slides and a tree 23 kilometers to the northwest in a probable tsunami deposit on the shore of Puget Sound died in the same season of the same year. The close coincidence among the most recent lake landslides, a probable tsunami, abrupt subsidence, and other possible seismic events gives evidence for a strong prehistoric earthquake in the Seattle region. PMID- 17742530 TI - Terrestrial carbon and nitrogen isotopic ratios from cretaceous-tertiary boundary nanodiamonds. AB - One hypothesis for the origin of the nanometer-size diamonds found at the Cretaceous-Tertiary (K-T) boundary is that they are relict interstellar diamond grains carried by a postulated asteroid. The (13)C/(12)C and (15)N/(14)N ratios of the diamonds from two sites in North America, however, show that the diamonds are two component mixtures differing in carbon and nitrogen isotopic composition and nitrogen abundance. Samples from a site from Italy show no evidence for either diamond component. All the isotopic signatures obtained from the K-T boundary are material well distinguished from known meteoritic diamonds, particularly the fine-grain interstellar diamonds that are abundant in primitive chondrites. The K-T diamonds were most likely produced during the impact of the asteroid with Earth or in a plasma resulting from the associated fireball. PMID- 17742531 TI - A high-resolution record of holocene climate change in speleothem calcite from cold water cave, northeast iowa. AB - High-precision uranium-thorium mass spectrometric chronology and (18)O-(13)C isotopic analysis of speleothem calcite from Cold Water Cave in northeast Iowa have been used to chart mid-Holocene climate change. Significant shifts in dagger(18)O and dagger(13)C isotopic values coincide with well-documented Holocene vegetation changes. Temperature estimates based on (18)O/(16)O ratios suggest that the climate warmed rapidly by about 3 degrees C at 5900 years before present and then cooled by 4 degrees C at 3600 years before present. Initiation of a gradual increase in dagger(13)C at 5900 years before present suggests that turnover of the forest soil biomass was slow and that equilibrium with prairie vegetation was not attained by 3600 years before present. PMID- 17742532 TI - Direct Detection of C4H2 Photochemical Products: Possible Routes to Complex Hydrocarbons in Planetary Atmospheres. AB - The photochemistry of diacetylene (C4H2), the largest hydrocarbon to be unambiguously identified in planetary atmospheres, is of considerable importance to understanding the mechanisms by which complex molecules are formed in the solar system. In this work, the primary products of C4H2's ultraviolet photochemistry were determined in a two-laser pump-probe scheme in which the products of C4H2 photoexcitation are detected by vacuum ultraviolet photoionization in a time-of-flight mass spectrometer. Three larger hydrocarbon primary products were observed with good yield in the C4H2* + C4H2 reaction: C6H2, C812, and C8H3. Neither C6H2 nor C8H3 is anticipated by current photochemical models of the atmospheres of Titan, Uranus, Neptune, Pluto, and Triton. The free hydrogen atoms that are released during the formation of the C8H3 and C8H2 products also may partially offset the role of C4H2 in catalysing the recombination of free hydrogen atoms in the planetary atmospheres. PMID- 17742533 TI - Electrical Resistivity and Stoichiometry of CaxC60 and SrxC60 Films. AB - The temperature- and concentration-dependent resistivities of annealed CaxC(60) and SrxC(60) films were measured near room temperature. Resistivity minima were observed at x = 2 and 5. The resistivities of these films were rho(min) approximately 1 ohm-centimeter for x = 2 and rho(min) approximately 10(-2) ohm centimeter for x = 5. This latter value is comparable to the resistivities found in similar experiments on K(3)C(60) films. There is a maximum in the resistivity between x = 2 and 3, and another at x approximately 7. The conductivity is activated over the whole range of compositions, and the activation energy scales with the logarithm of the resistivity. The results suggest that the conductivity and superconductivity observed in Ca(5)C(60) are associated with the population of bands derived from the t(1g) level of C(6O). PMID- 17742534 TI - Charge Donation by Calcium into the t1g Band of C60. AB - Photoemission spectra of compounds prepared by the reaction of C(60) films with calcium show two distinct metallic phases, whereas alkali-doped C(60) films have only one. In the first phase the bulk t(1u) band, derived from the lowest unoccupied molecular orbital of C(60), is partially occupied. This is followed by an insulating phase that has the composition Ca(3)C(60) in which the t(1u) band is filled and has properties analogous to those of K(6)C(60). Continued exposure to calcium produces a second metallic phase in which electrons are donated into the t(1g) band. The superconductivity of Ca(5)C(60) is associated with the t(1g) band. PMID- 17742535 TI - Electronic, magnetic, and geometric structure of metallo-carbohedrenes. AB - The energetics and the electronic, magnetic, and geometric structure of the metallocarbohedrene Ti(8)C(12) have been calculated self-consistently in the density functional formulation. The structure of Ti(8)C(12) is a distorted dodecahedron with a binding energy of 6.1 electron volts per atom. The unusual stability is derived from covalent-like bonding between carbon atoms and between titanium and carbon atoms with no appreciable interaction between titanium atoms. The density of states at the Fermi energy is high and is derived from a strong hybridization between titanium 3d and carbon sp electrons. Titanium sites carry a small magnetic moment of 0.35 Bohr magneton per atom and the cluster is only weakly magnetic. PMID- 17742536 TI - Temperature and size variabilities of the Western pacific warm pool. AB - Variabilities in sea-surface temperature and size of the Western Pacific Warm Pool were tracked with 10 years of satellite multichannel sea-surface temperature observations from 1982 to 1991. The results show that both annual mean sea surface temperature and the size of the warm pool increased from 1983 to 1987 and fluctuated after 1987. Possible causes of these variations include solar irradiance variabilities, EI Nino-Southern Oscillation events, volcanic activities, and global warming. PMID- 17742537 TI - EMF, an Arabidopsis Gene Required for Vegetative Shoot Development. AB - In higher plants, the transition from the vegetative to the; reproductive state in the shoot meristem initiates flowering. To study this floral transition, Constitutively flowering mutant of Arabidopsis thaliana ecotype columbia, embryonic flower (emf), was characterized. No vegetative shoots were produced from emf embryos or calli; the shoot apical meristems (SAMs) in the emf embryos were altered compared to wild-type SAMs. The mutant SAMs enlarged precociously and produced inflorescence meritems upon germination. These results suggest that the dominant, wild-type allele EMF is required for the vegetative state of the SAM. In the absence of EMF function, the mutant embryo assumes the reproductive state. PMID- 17742538 TI - A Homoeotic Mutant of Arabidopsis thaliana with Leafy Cotyledons. AB - Cotyledons are specialized leaves produced during plant embryogenesis. Cotyledons and leaves typically differ in morphology, ultrastructure, and patterns of gene expression. The leafy cotyledon (Iec) mutant of Arabidopsis thaliana fails to maintain this distinction between embryonic and vegetative patterns of plant development. Mutant embryos are phenotypically abnormal, occasionally viviparous, and intolerant of desiccation. Mutant cotyledons produce trichomes characteristic of leaves, lack embryo-specific protein bodies, and exhibit a vascular pattern intermediate between that of leaves and cotyledons. These results suggest that lec cotyledons are partially transformed into leaves and that the wild-type gene (LEC) functions to activate a wide range of embryo-specific pathways in higher plants. PMID- 17742539 TI - How parts of the brain compute. PMID- 17742540 TI - HTSC for Newcomers. PMID- 17742541 TI - Vignettes: fields of science. PMID- 17742542 TI - Cytotoxins and Cytoly-sins. PMID- 17742543 TI - Products & materials. PMID- 17742544 TI - AAAS Headquarters. PMID- 17742545 TI - Publications Received. PMID- 17742546 TI - Meetings & Conferences. PMID- 17742547 TI - Research in Psychiatry Is Starving to Death. PMID- 17742548 TI - The Effect of Drying Temperature on the Folic Acid Content of Herring Meal. PMID- 17742549 TI - Reactions of the Porpoise to Ultrasonic Frequencies. PMID- 17742550 TI - The Function of Vitamin C in the Adrenal Cortex. PMID- 17742552 TI - Examination of Human Fat for the Presence of DDT. PMID- 17742551 TI - Antitubercular Diazine Carboxamides. PMID- 17742553 TI - The Microdetermination of "Free" L-Tryptophane in the Seedling of Lupinus albus. PMID- 17742554 TI - Minimum Night Temperatures at or Near Full Moon. PMID- 17742556 TI - Fourmarier's Suction Theory of Geosynclines, and the "Vertical Push" Explanation of Geanticlinal Orogeny. PMID- 17742555 TI - Science Teaching in the Secondary Schools. PMID- 17742557 TI - Letters. PMID- 17742559 TI - Rebuttal. PMID- 17742560 TI - Deficiencies of "pass-fail". PMID- 17742558 TI - Letters. PMID- 17742561 TI - Deluged by conservation appeals. PMID- 17742562 TI - Clearer skies for astronomy. PMID- 17742563 TI - Mass transit: a cop out. PMID- 17742564 TI - Letters. PMID- 17742565 TI - The R & d processing of domestic programs. PMID- 17742566 TI - Lederberg opposes cancer authority. PMID- 17742567 TI - FAS: Reviving Lobby Battles ABM, Scientists' Apathy. PMID- 17742568 TI - Cost squeeze in higher learning. PMID- 17742569 TI - Stellar Old Age (III): Black Holes and Gravitational Collapse. PMID- 17742570 TI - Major element variation and possible source materials of apollo 12 crystalline rocks. AB - Nine different crystalline rocks of the Apollo 12 samples have been analyzed with conventional chemical rock analysis methods. Five of the rocks have normative quartz, whereas the others have normative olivine and hypersthene. The rocks show a wide range in the ratio of iron to magnesium, and their compositions fall on relatively smooth curves in the oxide variation diagram. It is suggested that these rocks, with one exception, represent different parts of a differentiated magmatic body, in which magmatic differentiation by crystallization and settling of olivine was most effective. The source material of the original magma may be peridotite with or without minor amounts of plagioclase or spinel or garnet, with the presence or absence of these minerals dependent on the depth of magma generation. PMID- 17742571 TI - Solar particle tracks in glass from the surveyor 3 spacecraft. AB - A glass filter from Surveyor 3 has a surface density of approximately 1 x 10(6) tracks per square centimeter from heavy solar flare particles. The variation with depth is best fitted with a solar particle spectrum dN/dE = 2.42 x 10(6) E(-2) [in particles per square centimeter per year per steradian per (million electron volts per nucleon)], where E is the energy and N is the number of particles, from 2 million electron volts per nucleon to approximately 7 million electron volts per nucleon and dN/dE = 1.17 x 10(7) E(-3) at higher energies. Not much difference is observed between 0.5 and 5 micrometers, an indication that there is a lack of track-registering particles below 0.5 million electron volts per nucleon. The Surveyor data are compatible with track results in lunar rocks, provided an erosion rate of approximately 10(-7) centimeter per year is assumed for the latter. The results also suggest a small-scale erosion process in lunar rocks. PMID- 17742572 TI - Very heavy solar cosmic rays: energy spectrum and implications for lunar erosion. AB - The energy spectrum of solar cosmic-ray particles of the iron group has been determined for the first time over the energy range from 1 to 100 million electron volts per nucleon by the use of glass removed from the Surveyor 3 spacecraft. The difference between the observed (energy)(-3) spectrum and the limiting spectrum derived previously from tracks in lunar rocks gives an erosion rate of 0 to 2 angstroms per year. High-energy fission of lead, induced by galactic cosmicray protons and alpha particles, has also been observed. PMID- 17742573 TI - Solar-climate relationships in the post-pleistocene. AB - The most conspicuous climatic aberration of the past two millennia was the temperature decline and glacial advance of the A.D. 1550 to 1900 period. This temperature decline has been correlated with an interval of lower solar activity and there is evidence from both the post-Pleistocene glacial record and from oxygen-18 analysis that such an interval han recurred at cyclic periods of around 2400 to 2600 years. PMID- 17742574 TI - Deep sea drilling: age and composition of an atlantic basaltic intrusion. AB - The fission track age of a basalt recovered from beneath Campanian sediments on the lower western flank of the Mid-Atlantic Ridge is (15.9 +/- 1.6) x 10(6) years. The major element composition of a glassy margin of the basalt is similar to that of oceanic tholeiites except for a markedly higher potassium concentration. PMID- 17742575 TI - Lunar and terrestrial ilmenite basalt. AB - A basalt hornfels from the Keweenawan Duluth complex in Minnesota contains 7 percent by weight of titanium dioxide and is similar in many respects to the Apollo 11 samples. Hornfels texture, as well as primary textures in lunar rocks, resemble those in Keweenawan rocks. PMID- 17742576 TI - Polymer whiskers grown from methyl 2-cyanoacrylate vapor. AB - Filaments of methyl 2-cyanoacrylate polymer were developed from the vapors of the monomer. While growing, the fibers seem to be chemically more active at their ends than along their sides, with this chemical specificity leading to a linearly ordered polymer structure. The number and character of the fibers are a function of the surface from which the fibers emanate and of the concentration of the monomer. PMID- 17742577 TI - Disjunct foliar veins in hawaiian euphorbias. AB - Isolated segments of veins occur in the leaf mesophyll of several Hawaiian species of Euphorbia. These anomalous structures appear to consist entirely of tracheids and are a normal feature of the anatomy of species native to mesic and wet areas, but not to xeric, dry habitats. PMID- 17742578 TI - Morphactin-induced parthenocarpy in the cucumber. AB - Parthenocarpy was induced in cucumber Cucumis sativus L. by foliar application of morphactin. Morphactin (chlorfluorenol) was most effective in inducing parthenocarpy when applied in the flowering stage, and the response was enhanced by prior treatment with Ethrel (2-chloroethylphosphonic acid). Morphactin stimulated pistillate flower development in a monoecious cultivar but did not modify sex expression of a gynoecious line. PMID- 17742579 TI - That Seventh Veil. PMID- 17742580 TI - Water: Can Cloud-Seeding Help? PMID- 17742582 TI - Education and Support of Scientists. PMID- 17742581 TI - Erratum: A Matter of Local Pride. PMID- 17742583 TI - Japan Points a Way. PMID- 17742584 TI - East Pacific Rise: The Magnetic Pattern and the Fracture Zones. PMID- 17742585 TI - Computer-Produced Movies. PMID- 17742586 TI - Ernst Mach: Biographical Notes. PMID- 17742587 TI - The University and the Exploration of Space. PMID- 17742589 TI - Auto Safety: New Study Criticizes Manufacturers and Universities. PMID- 17742588 TI - Oak Ridge National Laboratory: Aim Is Change along with Growth. PMID- 17742591 TI - Speaker Ban: State Assembly Kills Law Denying Forum To Communists; U. N. C.' s Status Is Believed Safe. PMID- 17742590 TI - Graduate Schools: Grants Awarded To Encourage Stronger Programs. PMID- 17742592 TI - Tenuous Surface Layer on the Moon: Evidence Derived from Radar Observations. AB - By radar backscattering, observations of the moon have been made which show a systematic difference between the backscattering coefficient of waves polarized in, and perpendicular to, the local plane of incidence. The results arein agreement with a model consisting of a tenuous top layer at least 10 centimeters thick, supported by a denser underlying layer. PMID- 17742593 TI - Mars: Compatible Determinations of Surface Pressure through Particle Scattering. AB - The number of scattering particles required to bring the visual polarimetric and ultraviolet photometric estimates of the surface pressure of Mars into agreement are calculated. Concentrations of 108 to 109 ice particles,0.2 micron in diameter, per square-centimeter column are obtained. Based on concentrations of Aitken nuclei in the atmosphere of Earth, a layer less than 100 meters thick would contain the required number of particles. The compatible pressures obtained in this manner for various N(2)-CO(2) and Ar-CO(2) atmospheric models lie within the range of pressures determined spectroscopically. PMID- 17742594 TI - Nitrogen: Formation by Photooxidation of Ethylene in the Presence of Its Oxides. AB - The apparent lack of nitrogen balance for the photooxidation systems containing olefin and nitrogen oxides can beexplained by evidence for the production of molecular nitrogen; molecular nitrogen was identified by gas chromatography and mass spectrometry. PMID- 17742595 TI - Volume Measurements on Chromium to Pressure of 30 Kilobars. AB - The unit cell volume of chromium was measured as a function of pressure from 1 bar to 30 kilobars by x-ray diffraction techniques. The antiferromagnetic transition occurred at 1.5 kilobars at 29 degrees C, where there is a discontinuity in the slope of the curve for lattice parameter vs. pressure. By electrical resistance measurements the value of -deltaT(N)/ deltaP was determined to be 5.9 degrees + 0.3 degrees per kilobar. At room temperature chromium remains in the body centered cubic crystal structure from 0 to 55 kilobars. PMID- 17742596 TI - Sea-Level Changes during the Last 2000 Years at Point Barrow, Alaska. AB - Eustatic rises of sea level between A. D. 265 and 500 and between A. D. 1000 and 1100 caused the formation of raised beaches. After the first rise, sea level dropped about2 meters below the present level, permitting Eskimo settlement of Birnirk about A. D. 500. The second rise of the ocean flooded Birnirk. At present, sea level is about 0.6 to 1.0 meter below the highwater levels; the ocean partially floods Birnirk. PMID- 17742597 TI - Energy Intake of the Mouring Dove Zenaidura macroura marginella. AB - Wild mourning doves follow a discrete cycle of feeding activity. Analysis of their food habits has provided an estimate for their average daily caloric intake. PMID- 17742598 TI - Bacterial Stimulation of Sporangium Production in Phytophthora cinnamomi. AB - Bacteria, notably Chromobacterium violaceum, stimulate initiation of production of sporangia by Phytophthora cinnamomi, a plant pathogen which does not produce this asexual stage in ordinary agar or liquid culture. PMID- 17742600 TI - Steroid Hormones and the Pill. PMID- 17742601 TI - Forthcoming Events. PMID- 17742599 TI - Iodine: Accumulation by Balanoglossus gigas. AB - The whole body of the giant Brazilian enteropneust, Balanoglossus gigas, shows an accumulation of iodine, but theconcentration in the hepatic region is 854.7 percent higher than it is in the proboscis, where the amount of iodine is the lowest. Such an iodine concentration has not yet been detected in any other enteropneust or protochordate. PMID- 17742604 TI - What price the lunar rocks? PMID- 17742603 TI - Social science research. PMID- 17742602 TI - Arabidopsis Research. PMID- 17742606 TI - Letters to the editor. PMID- 17742605 TI - A name to fit the crime. PMID- 17742607 TI - Threatened faculty pensions. PMID- 17742608 TI - Orbital symmetry control of chemical reactions. PMID- 17742609 TI - Search for hidden chambers in the pyramids. PMID- 17742610 TI - Son of technology gap: European group setting up an institute. PMID- 17742612 TI - Astronomical theory of climatic change: support from new Guinea. AB - Radiocarbon and thorium-230 dates of uplifted coral reef terraces on New Guinea appear to support theories of glaciation which utilize Milankovitch cycles as a controlling trigger mechanism. In addition to high sealevel stands recognized by other workers, the New Guinea data clearly indicate a marine transgression between 50,000 and 35,000 years before the present. A eustatic sea level curve reconstructed from field observations and radiometric dates shows a close correlation with temperature fluctuations in high latitudes as predicted by astronomical data. PMID- 17742613 TI - Polywater: methods for identifying polywater columns and evidence for ordered growth. AB - The refractive indices of polywater columns in glass capillaries have been rapidly and accurately measured with an interference microscope. Polywater has been detected by this method in both quartz and Vycor glass capillaries. A comparison of refractive index measurements with measurements of optical anisotropy indicates that polywater initially condenses with an ordered structure. PMID- 17742614 TI - Rangia cuneata on the East Coast: Thousand Mile Range Extension, or Resurgence? AB - Rangia cuneata, a valuable clam of the estuarine zone where fluctuating salinities (from 0 to 15 parts per thousand) exclude most animals, is now developing large populations in many estuaries from Florida to Maryland. Before 1955 it was thought to be extinct on the East Coast since the Pleistocene and to be living only in Gulf Coast estuaries. PMID- 17742615 TI - Dextranase activity in coleoptiles of Avena. AB - Ani enzyme activity similar to that of dextranase is associated with coleoptiles of Avena sativa. When subjected to purified dextranase, both the pure natural dextran and the cell walls of the Avena coleoptiles yield isomaltose and isomaltotriose. Thus, the cell walls contain dextrans or dextran-like compounds. Coleoptiles with low auxin content have a lower dextranase activity than coleoptiles with high auxin content. The enzyme activity is therefore in some way sensitive to thle hormone. PMID- 17742616 TI - Barley yellow dwarf virus: phenotypic mixing and vector specificity. AB - Although the aphid Rhopalosiphum padi does not regularly transmit the MAV isolate of barley yellow drawf virus from singly infected oats, it often transmits MAV, together with the serologically unrelated RPV isolate, from plants doubly infected by MAV and RPV. Vector specificity of the virus isolates appears to be a function of the virus capsid. Some MAV nucleic acid becomes coated with RPV capsid protein during simultaneous synthesis of the two isolates in the doubly infected plant. PMID- 17742617 TI - Blue haze and mariner 6 pictures of Mars. PMID- 17742618 TI - Adaptive aspects of insular evolution. PMID- 17742620 TI - This week in science. PMID- 17742619 TI - Aspen conference on quantum crystals. PMID- 17742621 TI - On institutional memory. PMID- 17742623 TI - Hominid evolution. PMID- 17742624 TI - Hominid evolution. PMID- 17742622 TI - Reproducing results. PMID- 17742625 TI - A Mass Extinction Without Asteroids: Although the data are still swathed in uncertainty, biologists have an increasing sense of urgency about the accumulating extinction of species through tropical deforestation; the loss could equal some of the largest of the mass extinctions of the geological record. PMID- 17742626 TI - Return of the Locust: A Cloud Over Africa: Last year's rains brought better harvests--and a bigger crop of locusts and, grasshoppers, threatening a revival of the plagues of the past. PMID- 17742627 TI - Going with the wind. PMID- 17742628 TI - ICSU Gives Green Light To Global Change Study. PMID- 17742629 TI - Senate Committee Boosts NSF's Budget Prospects. PMID- 17742630 TI - Quantum Jumps Seen In a Single Ion: Researchers can monitor an infrequently occurring quantum transition in a single ion as it happens by measuring the fluorescence due to a frequently occurring transition. PMID- 17742631 TI - Supply-Side Ecology: Existing models of population structure and dynamics of ecological communities have tended to ignore the effect of the influx of new members into the communities. PMID- 17742632 TI - NMR studies of simple molecules on metal surfaces. AB - In recent years, improvements in the sensitivity of nuclear magnetic resonance have made it possible to detect progressively smaller numbers of nuclei. Experiments and studies previously thought to be impractical can now be undertaken, for example, the study of phenomena at surfaces. Nuclear magnetic resonance has been applied to study simple molecules (carbon monoxide, acetylene, and ethylene) adsorbed on metal surfaces (ruthenium, rhodium, palladium, osmium, iridium, and platinum). The metals, in the form of clusters 10 to 50 angstroms in diameter, supported on alumina, are typical of real catalysts. The experiments provide information about the bonding of the molecules to the metal, the structures the molecules assume after adsorption, the motion of molecules on the surface, the breakup of molecules induced by heating, and the products of such breakup. PMID- 17742633 TI - Interpreting interpersonal behavior: the effects of expectancies. AB - Attempts to understand the personal characteristics of others, in interactions with them, are complicated by the fact that one tends to find what one expects. This happens not only because processing of information is selective, but also because expectancies cause one to act in ways that elicit behavior interpretable as confirming those expectancies, even when the expectancies might have been mistaken. Studies provide ample evidence of such self-fulfilling prophecies in social interaction and are beginning to spell out the crucial steps in the process for confirming expectancies. Such studies help link the psychology of first impressions to the psychology of long-term relationships by showing how expectancies are sustained or modified through behavioral sequences that are partially determined by initial expectancies. PMID- 17742634 TI - Laboratory experiments on planetary and stellar convection performed on spacelab 3. AB - Experiments on thermal convection in a rotating, differentially heated hemispherical shell with a radial buoyancy force were conducted in an orbiting microgravity laboratory. A variety of convective structures, or planforms, were observed, depending on the magnitude of the rotation and the nature of the imposed heating distribution. The results are compared with numerical simulations that can be conducted at the more modest heating rates, and suggest possible regimes of motion in rotating planets and stars. PMID- 17742635 TI - The proterozoic ophiolite problem, continental emergence, and the venus connection. AB - To account for the lack of preservation of ophiolites (fragments of oceanic crust and mantle) in old orogenic belts (age 1000 to 2500 million years), a hypothesis proposes that the magmatic oceanic crust formed during sea-floor spreading was thicker during the cited time interval. This thickening led to reduced contrast between the elevation of continental and oceanic regions and to greater average flooding of the continents. The resultant distribution of elevation may have resembled modern Venus more than modern Earth. PMID- 17742636 TI - Cliff swallow colonies as information centers. AB - Colonies of cliff swallows (Aves: Hirundo pyrrhonota) appear to be information centers in which colony residents acquire information on the location of food sources. Individuals that have been unsuccessful on a foraging trip return to the colony, locate a successful forager, and follow that individual to a food source. Individuals often follow, and are followed by, their neighbors within the colony, possibly because neighbors can observe foraging success through food brought back to nestlings. All individuals are equally likely to follow others or be followed, and thus all individuals benefit from opportunities to receive information. PMID- 17742637 TI - Association's Work In Argentina Featured in NOVA's Season Premier. PMID- 17742638 TI - D.C. Members--TV and Radio Reviewers Needed. PMID- 17742640 TI - AAAS' Malcom Receives Award. PMID- 17742639 TI - Proposals and resolutions invited for 1987 council meeting. PMID- 17742642 TI - Reminder to Member--AAAS Elections Are Under Way. PMID- 17742641 TI - Ethics society group meets this month. PMID- 17742643 TI - AAAS Publications Catalog Available. PMID- 17742644 TI - Philadelphia science seminar series for teachers under way this fall. PMID- 17742645 TI - National forum for school science: forum '86: the science curriculum. PMID- 17742646 TI - The academic profession:american professors. PMID- 17742647 TI - Applications of group theory: group structure of gauge theories. PMID- 17742648 TI - The legal system as social: an invitation to law and social science. PMID- 17742650 TI - Ices: ices in the solar system. PMID- 17742649 TI - Reprints of books previously reviewed. PMID- 17742651 TI - Products & materials. PMID- 17742652 TI - SCIENTIFIC SURVEYS OF THE PHILIPPINE ISLANDS. PMID- 17742654 TI - DISCUSSION AND CORRESPONDENCE. PMID- 17742653 TI - ANTHROPOLOGY AND ITS LARGER PROBLEMS. PMID- 17742655 TI - ON THE HABITS OF THE GREAT WHALE SHARK (RHINEODON TYPUS). PMID- 17742657 TI - THE MAILED CATFISHES OF SOUTH AMERICA. PMID- 17742656 TI - A FAUNAL SURVEY OF THE FOREST RESERVES IN THE SANDHILL REGION OF NEBRASKA AND OF THE LAKES IN THAT REGION. PMID- 17742659 TI - Editorial. PMID- 17742658 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17742660 TI - A National Science Foundation and the Scientific Worker. PMID- 17742662 TI - Wartime Research in Malaria. PMID- 17742661 TI - Alliance of Industry and Scientific Research in Great Britain. PMID- 17742663 TI - Science Legislation and the Holiday Recess. PMID- 17742664 TI - The Lipotropic Properties of Inositol. PMID- 17742665 TI - TDE, 1,1-Dichloro-2,2-bis(p-chlorophenyl) ethane, as an Anopheline Larvicide. PMID- 17742666 TI - The Age of Jerome Bog, "A Carolina Bay". PMID- 17742667 TI - Sintered Glass Disks. PMID- 17742669 TI - A Potometer for Rapid Measurements of Ingestion by Haustellate Insects. PMID- 17742668 TI - Black Fly Incubator-aerator Cabinet. PMID- 17742670 TI - Attachment of Electroencephalographic Electrodes. PMID- 17742671 TI - A New Glass Device for Staining Cover-Glass Preparations. PMID- 17742672 TI - The Best Defense. PMID- 17742673 TI - Some X-Ray Crystallographic Data on DDT. PMID- 17742674 TI - The Pelletier and Caventou Monument in Paris. PMID- 17742675 TI - Growth of Trophoblast in the Anterior Chamber of the Eye of the Rabbit. PMID- 17742676 TI - The Rumbling of Thunder. PMID- 17742677 TI - Information Please. PMID- 17742678 TI - On Opening "Frozen" Vacuum Desiccators. PMID- 17742679 TI - A Correction. AB - In a recent note, "A possible explanation of ;freezing' behavior in rats" (Bernard F. Riess. Science, 1945, 102, 570), the author was guilty of a serious omission which completely vitiated the meaning of the article. A comparison was made between two groups of animals, one living in multiple-animal cages, the other in isolation. In giving a description of the groups, the population of the multiple-housed animals was given as 124 and that of the second group was inadvertently omitted. There were 84 animals in this second group. This makes it possible to evaluate the difference between the two groups. The author apologizes for the omission. PMID- 17742680 TI - "Freezing" Behavior in Rats. PMID- 17742681 TI - Catalogue Corner. PMID- 17742682 TI - NOT TEN BUT TWELVE! PMID- 17742683 TI - A NATIONAL INSTITUTE OF NUTRITION. PMID- 17742684 TI - THE OSLER PRESENTATION. PMID- 17742685 TI - THE IMPERFECT STAGE OF LEPTOSPHAeRIA TRITICI OF WHEAT. PMID- 17742686 TI - A POSSIBLE SOURCE OF COSMICAL ENERGY. PMID- 17742687 TI - ORGANIZATION OF THE AMERICAN SECTION OF THE INTERNATIONAL GEOPHYSICAL UNION. II. PMID- 17742688 TI - APPENDIX: REPORT OF THE COMMITTEE ON INVESTIGATION OF EARTH TIDES. PMID- 17742689 TI - RESEMBLANCES BETWEEN THE PROPERTIES OF SURFACE-FILMS IN PASSIVE METALS AND IN PROTOPLASM. I. PMID- 17742690 TI - A Century of Entomology. PMID- 17742691 TI - Meetings & Conferences. PMID- 17742692 TI - Miscellaneous Publications. PMID- 17742693 TI - Graphitization of Diamond. PMID- 17742694 TI - OBSERVATIONS ON SIREDON LICHENOIDES. PMID- 17742695 TI - NOTE ON PHOTOGRAPHS OF THE SPECTRUM OF THE COMET OF JUNE, 1881. PMID- 17742696 TI - AMYLOSE. PMID- 17742697 TI - A MICROSCOPICAL STUDY OF THE IRON ORE, OR PERIDOTITE OF IRON MINE HILL, CUMBERLAND, RHODE ISLAND. PMID- 17742698 TI - AN ANALYSIS OF WATER DESTRUCTIVE TO FISH IN THE GULF OF MEXICO. PMID- 17742699 TI - DO WE SEE NON-LUMINOUS BODIES BY REFLECTED LIGHT? PMID- 17742700 TI - COMET (b), 1881. PMID- 17742701 TI - ADULTERATION OF SUGAR. PMID- 17742702 TI - ASTRONOMICAL NOTE. PMID- 17742703 TI - COMET (c) 1881. PMID- 17742705 TI - To the Editor of "SCIENCE". PMID- 17742704 TI - To the Editor of "Science.". PMID- 17742706 TI - A PARASITE IN AeGEIRA SYRINGAe. HARR. PMID- 17742707 TI - TRICHINAe IN RATS. PMID- 17742708 TI - THE REVIVAL OF ORGANIC CHEMISTRY. PMID- 17742709 TI - THE WAIKURU, SERI AND YUMA LANGUAGES. PMID- 17742710 TI - ON THE INFLECTION OF THE ANGLE OF THE JAW IN THE MARSUPIALIA. PMID- 17742711 TI - OKLAIHOMA GEOLOGICAL SURVEY. PMID- 17742713 TI - SCIENTIFIC JOURNVALS AND ARTICLES. PMID- 17742712 TI - MOSQUITOES OF THE UNITED STATES. PMID- 17742714 TI - AN EMINENT AMERICAN MAN OF SCIENCE. PMID- 17742715 TI - MUSEUM AND ZOOLOGICAL NOTES. PMID- 17742716 TI - NOTES ON INORGANIC CHEMISTRY. PMID- 17742717 TI - THE AGE OF THE BIG TREES OF CALIFORNIA. PMID- 17742719 TI - THE AMERICAN PUBLIC HEALTH ASSOCIATION. PMID- 17742718 TI - THE BIG TREES OF CALIFORNIA. PMID- 17742721 TI - LOCAL DESCRIPTIVE FLORAS. PMID- 17742720 TI - THE MRS. CURTISS MEMORIAL. PMID- 17742722 TI - Nuclear reaction rates in stars. PMID- 17742723 TI - Achievement by the disadvantaged. PMID- 17742724 TI - NIH Grants Cover Page Charges. PMID- 17742725 TI - Malaria: a problem for all time. PMID- 17742726 TI - Engineering: renew its luster. PMID- 17742727 TI - Beings from outer space--corporeal and spiritual. PMID- 17742728 TI - Ion implantation studies in silicon. PMID- 17742729 TI - Apollo: how the United States decided to go to the moon. PMID- 17742730 TI - Senate: new leaders for health and education. PMID- 17742731 TI - Un-fair harvard?: faculty report surveys university-city relations. PMID- 17742732 TI - Satellite Observations of the Earth's Radiation Budget. AB - Meteorological satellites have provided the first complete data on energy exchange between earth and space. The planetary albedo is 29 percent for the mean annual case, and the entire earth-atmosphere system is in near radiative equilibrium. More energy is absorbed in tropical regions than previously believed, and major energy source and sink regions exist within latitude belts. PMID- 17742733 TI - Water on the moon and a new nondimensional number. AB - A nondimensional number called the Jeffreys number, which represents the ratio of the Reynolds number to the Froude number, is useful in geophysical problems related to the motion of viscous masses under gravity. The Jetireys number is used to show that it is impossible for the lunar maria to be underlain by a layer of material 1 kilometer thick having the plastic properties of ice. PMID- 17742735 TI - Hoabinhian: a pebble-tool complex with early plant associations in southeast Asia. AB - The term "Hoabinhian" has been applied to "mesolithic" assemblages from all parts of mainland Southeast Asia. Recent excavation in north Thailand has yielded the first associated carbon-14 dates and provided evidence for the early (about 7000 B. C.) domestication of plants in Southeast Asia. PMID- 17742734 TI - Fossil mycelium with clamp connections from the middle pennsylvanian. AB - A mycelium with clamp connections and chlamydospores has been discovered within the wood of a Middle Pennsylvanian fern. This suggests that forms extant in the middle of the Pennsylvanian had life cycles conparable to some modern Basidiomnycetes. PMID- 17742736 TI - Environmental temperatures of tertiary penguins. AB - Marine paleotemperatures, determined by oxygen isotope measurement, show that Australasian Tertiary penguins, including giant forms, lived in warm to tropical environments. Evolution from smaller species also occurred in warm environments. Mid-Tertiary fluctuations of sea temperature were controlled by alternating uplift and erosion of "Tasmantis," an unstable meridional landmass occupying and extending beyond the present position of New Zealand. PMID- 17742737 TI - Viscosity of argon at high temperatures. AB - New data for the viscosity of argon at high temperatures indicate that the accepted data are substantially too low at temperatures above 600 degrees K. PMID- 17742738 TI - Microtubules in spermatozoa of childia (turbellaria, acoela) revealed by negative staining. AB - Many intact axial units, with attached basal plates, are found in spermatozoa of Childia groenlandica negatively stained with phosphotungstic acid. Electron micrographs show a total of nine doublet microtubules, confirming observations on sectioned material, where nine peripheral doublets, but no single central ones, occurred. Living spermatozoa move by waves progressing along a double undulating membrane. PMID- 17742739 TI - Punishment by response-contingent withdrawal of an imprinted stimulus. AB - Newly hatched ducklinigs were exposed to a moving, imprinted stiulullls; if they followed it, the stimnulus was withdrawn briefly. The tendency to follow gradually declined durinig punishment periods, but it returned to prepunishment amounts whlen punishmnent terminated. This finding attests to the efficacy of withdrawal of reinforcement as a techniquie for behavioral control. PMID- 17742740 TI - Mosaic numbers. PMID- 17742742 TI - Air pollution medical research. PMID- 17742741 TI - Hypothalamic stimulation of growth hormone secretion. PMID- 17742743 TI - This week in science. PMID- 17742745 TI - Corrections and clarifications. AB - Figure 1, D, E, and F, on page 1564 of the report "Calcium entry through kainate receptors and resulting potassium-channel blockade in Bergmann glial cells" by T. Muller et al. (12 June, p. 1563) was printed incorrectly. The correct figure parts are printed below. [See figure in the PDF file]. PMID- 17742744 TI - Agricultural research. PMID- 17742746 TI - Science scope. PMID- 17742747 TI - And the States shall rise again? PMID- 17742748 TI - A threat to graduate research. PMID- 17742749 TI - Vapor Lock Linked to NASA's Tether Trouble. PMID- 17742750 TI - Beach buggy from the cambrian. PMID- 17742751 TI - Academic departments get stay. PMID- 17742753 TI - Mapping the river in the sky. PMID- 17742752 TI - Found: a universe in balance? PMID- 17742754 TI - The huastec region: a second locus for the production of bronze alloys in ancient mesoamerica. AB - Chemical analyses of 51 metal artifacts, one ingot, and two pieces of intermediate processed material from two Late Post Classic archeological sites in the Huastec area of Eastern Mesoamerica point to a second production locus for copper-arsenic-tin alloys, copper-arsenic-tin artifacts, and probably copper-tin and copper-arsenic bronze artifacts. Earlier evidence had indicated that these bronze alloys were produced exclusively in West Mexico. West Mexico was the region where metallurgy first developed in Mesoamerica, although major elements of that technology had been introduced from the metallurgies of Central and South America. The bronze working component of Huastec metallurgy was transmitted from the metalworking regions of West Mexico, most likely through market systems that distributed Aztec goods. PMID- 17742755 TI - Mechanisms of Porphyroblast Crystallization: Results from High-Resolution Computed X-ray Tomography. AB - Quantitative three-dimensional analysis of rock textures is now possible with the use of high-resolution computed x-ray tomography. When applied to metamorphic rocks, this technique provides data on the sizes and positions of minerals that allow mechanisms of porphyroblast crystallization to be identified. Statistical analysis of the sizes and spatial disposition of thousands of garnet crystals in three regionally metamorphosed rocks with diverse mineralogies, in conjunction with simple numerical models for crystallization, reveals in all cases the dominance of crystallization mechanisms whose kinetics are governed by rates of intergranular diffusion of nutrients. PMID- 17742756 TI - Mount pinatubo aerosols, chlorofluorocarbons, and ozone depletion. AB - The injection into the stratosphere of large quantities of sulfur during the June 1991 eruption of Mount Pinatubo (Philippines) and the subsequent formation of sulfate aerosol particles have generated a number of perturbations in the atmosphere with potential effects on the Earth's climate. Changes in the solar and infrared radiation budget caused by the eruption should produce a cooling of the troposphere and a warming of the lower stratosphere. These changes could affect atmospheric circulation. In addition, heterogeneous chemical reactions on the surface of sulfate aerosol particles render the ozone molecules more vulnerable to atmospheric chlorine and hence to man-made chlorofluorocarbons. PMID- 17742757 TI - Manganese flux from continental margin sediments in a transect through the oxygen minimum. AB - The flux of manganese from continental margin sediments to the ocean was measured with a free-vehicle, benthic flux chamber in a transect across the continental shelf and upper slope of the California margin. The highest fluxes were observed on the shallow continental shelf. Manganese flux decreased linearly with bottom water oxygen concentration, and the lowest fluxes occurred in the oxygen minimum zone (at a depth of 600 to 1000 meters). Although the flux of manganese from continental shelf sediments can account for the elevated concentrations observed in shallow, coastal waters, the flux from sediments that intersect the oxygen minimum cannot produce the subsurface concentration maximum of dissolved manganese that is observed in the Pacific Ocean. PMID- 17742758 TI - Siderophile Elements and the Earth's Formation. PMID- 17742759 TI - Siderophile Elements and the Earth's Formation. PMID- 17742760 TI - Response. PMID- 17742761 TI - A statement of principles. PMID- 17742763 TI - Tracking phytochrome. PMID- 17742762 TI - Consciousness redux. PMID- 17742765 TI - Products & materials. PMID- 17742766 TI - The Author as Indexer. PMID- 17742764 TI - An initiation in physics. PMID- 17742768 TI - Equal but Separate. PMID- 17742767 TI - Criteria for Research Grants. PMID- 17742769 TI - Interior of the Moon: Observations from space vehicles will provide further clues to the history of the earth-moon system. PMID- 17742770 TI - On The Unity of the Sciences: Interreactions among the physical and biological sciences show that unification is progressive. PMID- 17742771 TI - Disarmament: U.N. Agrees To Cancel Public Debate While U.S. and U.S.S.R. Talk Things Over. PMID- 17742772 TI - Vessels in Roots of Marsilea. AB - The occurrence of vessel members in the roots and the possible occurrence of sieve-tube members in the rhizome is reported for the first time in the heterosporous fern Marsilea quadrifolia. This discovery adds a new instance of parallel evolution of vessels in vascular plants. PMID- 17742773 TI - Fallout Radioactivity in Cattle and Its Effects. AB - The levels of strontium-90 and cesium-137 in cattle grazed on the Nevada Test Site and elsewhere in Nevada are similar to those in cattle from other parts of the country. Gastrointestinal absorption of the relatively large amounts of radioactive cerium-praseodymium, ruthenium-rhodium, and zirconium-niobium present in the rumina is very small. Zinc-65 made its first appearance in samples of muscle and liver in November 1958 and has persisted in later samplings. There has been no evidence of biological damage to date, either histologically or grossly. PMID- 17742774 TI - Seasonal Evisceration in the Sea Cucumber, Parastichopus californicus (Stimpson). PMID- 17742775 TI - Radioactive Dating of Tertiary Plant-Bearing Deposits. AB - Four potassium-argon determinations from Tertiary rocks in the interior of British Columbia have yielded dates ranging from 45 to 49 million years. This suggests contemporaneity of three separate localities within the Middle Eocene epoch. Abundant plant micro- and macrofossils support this conclusion and indicate a flora quite different from floras of comparable age in western United States. PMID- 17742777 TI - Forthcoming Events. PMID- 17742778 TI - EDWARD ORTON, GEOLOGIST. PMID- 17742776 TI - Formation of Free Radicals in Tritiated H2O and D2O Ice. AB - By using tritium as an internal source of radiation, electron spin resonance spectra may be obtained for samples contained in glass without the usual disturbing effects due to irradiated glass. The production of OH and OD radicals in tritiated H(2)O and D(2)O ice may be readily demonstrated with this technique. PMID- 17742779 TI - ON THE PATH OF THE FIREFLY WHILE PERIODICALLY FLASHING. PMID- 17742780 TI - PATENTS FOR ACTS OF NATURE. PMID- 17742781 TI - MICROBIOLOGY OF COAL. PMID- 17742782 TI - SPACE PERCEPTION BY RADIO. PMID- 17742783 TI - THE FIRST SOUTH AMERICAN BOTANICAL CONGRESS. PMID- 17742784 TI - SEX MECHANISM IN POLYPLOIDS OF MELANDRIUM. PMID- 17742786 TI - MOVEMENT OF RADIOPHOSPHORUS IN BEAN SEEDLINGS. PMID- 17742785 TI - BROAD PROTECTIVE ACTION OF RABBIT ANTIPNEUMOCOCCUS SERUM IN RATS. PMID- 17742787 TI - THE AVAILABILITY OF MANGANESE IN AVIAN DIGESTION. PMID- 17742788 TI - THE PROBLEM OF ORGANIZATION. PMID- 17742789 TI - THE GROWTH OF CHILDREN. PMID- 17742790 TI - THE WORK DONE BY THE GERMAN SUBCOMMITTEE ON THE TEACHING OF MATHEMATICS. PMID- 17742792 TI - A POSSIBLE CAUSE OF ACCIDENTS TO AVIATORS. PMID- 17742791 TI - THE NINETEENTH INTERNATIONAL CONGRESS OF AMERICANISTS, 1914. PMID- 17742793 TI - INSECTS CONTRIBUTING TO THE CONTROL OF THE CHESTNUT BLIGHT DISEASE. PMID- 17742794 TI - THE PEDOMETER. PMID- 17742796 TI - FAT DEPOSITION IN THE TESTIS OF THE DOMESTIC FOWL. PMID- 17742795 TI - A VOTE ON THE PRIORITY RULE BY THE AMERICAN SOCIETY OF ZOOLOGISTS, CENTRAL BRANCH. PMID- 17742797 TI - ECONOMIC IMPORTANCE OF THE MITE PHYLLOCOPTES SCHLECHTENDALI NALEPA. PMID- 17742798 TI - A NOTE ON THE STAR-NOSED MOLE. PMID- 17742799 TI - A PARAFFIN BATH WITH CONCEALED THERMO-ELECTRIC REGULATOR. PMID- 17742800 TI - A SIMPLE DISCHARGE TUBE FOR DEMONSTRATION PURPOSES. PMID- 17742801 TI - THE CONVOCATION WEEK MEETINGS OF SCIENTIFIC SOCIETIES. PMID- 17742802 TI - Punctuated equilibrium and the fossil record. PMID- 17742803 TI - Punctuated equilibrium and the fossil record. PMID- 17742804 TI - Perspective on agricultural research. PMID- 17742805 TI - Mariner Mark II and the Exploration of the Solar System. AB - Mariner Mark II is a concept for the next generatioon of deep-space missions. The project would provide limited, focused sets of Voyager- and Galileo-quality planetary observations at a fraction of the cost of the Voyager and Galileo projects. This article discusses Mariner Mark II's cost goals, scientific objectives, and mission requirements. Strategies for limiting costs include the use of a reconfigurable spacecraft, a multimission ground-support system, and selected new technologies. PMID- 17742806 TI - The threat of soil erosion to long-term crop production. AB - National increases in row crops at the expense of hay and pasture crops, particularly on steeper slopes, have made the control of erosion a difficult prospect. Management practices that fit the various field conditions are needed to accomplish effective erosion control. These measures should be selected on the basis of soil characteristics, landscape type, and the amount of ongoing erosion. The maintenance of a cropland base adequate to our needs must be a primary national goal. PMID- 17742807 TI - Reagan refuses to budge in weapons talks. PMID- 17742808 TI - Who's Who in the Social and Behavioral Sciences. PMID- 17742809 TI - Top Health Policy Official Leaving OSTP. PMID- 17742810 TI - Reagan orders review of controls on research. PMID- 17742811 TI - Catalysis: "no longer a black art". PMID- 17742812 TI - CERN Reports First Vector Boson Evidence. PMID- 17742813 TI - 1982 annual report of the executive officer. PMID- 17742814 TI - AAAS Members Share Their Experience with Local Science Museums. PMID- 17742815 TI - Western divisions will meet together in 1983. PMID- 17742817 TI - Grants Offered to Foreign Graduate Students to Attend AAAS Meeting. PMID- 17742816 TI - For the library. PMID- 17742818 TI - Membership dues increase announced. PMID- 17742819 TI - AAAS Socio-Psychological Prize. PMID- 17742820 TI - R&D, high technology, and economic recovery. PMID- 17742821 TI - Extrachromosomal genetics. PMID- 17742822 TI - Developmental neurobiology. PMID- 17742823 TI - Ancient Earth processes. PMID- 17742824 TI - Paleoclimatology. PMID- 17742825 TI - Ammonium-nitrogen in green river formation oil shale. AB - It has been assumed that all of the nitrogen in oil shale from the Green River Formation is present as organic nitrogen and that the nitrogen in spent shale from retorting is present in the char or coke. In fact, from 41 to 84 percent of the nitrogen is present as ammonium fixed within silicate minerals in five samples of raw oil shale and between 46 and 69 percent of the nitrogen is similarly fixed in two samples of spent shale. Both organic nitrogen and fixed ammonium-nitrogen are lost during retorting by the Fischer assay procedure; the loss of organic nitrogen is greater. PMID- 17742826 TI - Clay mineralogy of the cretaceous-tertiary boundary clay. AB - Analyses of the clay mineralogy of samples from the Cretaceous-Tertiary boundary layer at four localities show that the boundary clay is neither mineralogically exotic nor distinct from locally derived clays above and below the boundary. The significant ejecta component in the clay that is predicted by the asteroid-impact scenario was not detected. PMID- 17742827 TI - Leaf dimorphism in aquatic angiosperms: significance of turgor pressure and cell expansion. AB - Depending on environmental conditions, the aquatic angiosperm Callitriche heterophylia can develop two different leaf types with distinctive morphological characteristics. Cellular turgor pressure seems to act as the biophysical mechanism responsible for the selection of leaf form in control conditions designed to mimic the natural habitat of this plant. The experimental induction of leaf form involves the ability of various treatments to mediate cell expansion through their effects on turgor pressure or wall extensibility. PMID- 17742829 TI - Thermoregulation and Mate-Selection in Fowler's Toads? PMID- 17742828 TI - A fossil noctuid moth egg from the late cretaceous of eastern north america. AB - A moth egg assignable to the family Noctuidae (Lepidoptera) is described from 75 million-year-old sediments from Martha's Vineyard, Massachusetts. This sample, which extends the fossil record of this farnily and modern heteroneuran moths back to the Cretaceous, may provide insight into the coevolution of moths and flowering plants, as well as have implications for the evolution of bats. PMID- 17742830 TI - Thermoregulation and Mate-Selection in Fowler's Toads? PMID- 17742831 TI - Letters to the editor. PMID- 17742832 TI - Letters to the editor. PMID- 17742833 TI - Letters to the editor. PMID- 17742834 TI - Letters to the editor. PMID- 17742835 TI - Letters to the editor. PMID- 17742836 TI - More power--more pollution. PMID- 17742838 TI - Venus: a joint u.s.-U.s.s.R. Exploration program. PMID- 17742837 TI - Letters to the editor. PMID- 17742839 TI - Environmental problems. PMID- 17742841 TI - Confrontation or cooperation in the cornfield. PMID- 17742840 TI - Where are the jobs? PMID- 17742842 TI - Earthquake prediction and control. PMID- 17742843 TI - Conservation law I: seeking a breakthrough in the courts. PMID- 17742845 TI - British dons' ire raised by request to account for time. PMID- 17742846 TI - Fort detrick: redeployment? PMID- 17742847 TI - Senators discuss postwar economy. PMID- 17742848 TI - Apollo 11 solar wind composition experiment: first results. AB - The helium-4 solar wind flux during the Apollo 11 lunar surface excursion was (6.3 +/- 1.2) x 10(6) atoms per square centimeter per second. The solar wind direction and energy are essentially not perturbed by the moon. Evidence for a lunar solar wind albedo was found. PMID- 17742849 TI - Interglacial high sea levels and the control of greenland ice by the precession of the equinoxes. AB - The precession of the equinoxes appears to control the occurrence of high sea levels by partial or even total melting of the Greenland ice cap during interglacial ages. PMID- 17742850 TI - Phosphorus-proton spin-spin coupling and conformation of a dinucleoside phosphate. AB - The phosphorus-31 nuclear magnetic resonance spectrum of beta-adenosine-3'-beta adenosine-5'-phosphoric acid in its aqueous solution (pH = 9.2) was studied. The signal consisted of eight peaks caused by the spin-spin coupling of the phosphorus nucleus with three protons, two on the 5' carbon, and one on the 3' carbon. The coupling constants were 3.4, 6.5, and 8.1 hertz; from these values the dihedral angles of the three P-O-C-H systems were estimated. PMID- 17742851 TI - Molasse facies: records of worldwide crustal stresses. AB - Predominantly nonmarine molasse deposits in the Tethyan and Cordilleran mobile belts record major variations in orogenic activity in latest Cretaceous to earliest Cenozoic, mid-Cenozoic, and latest Cenozoic time. During the same intervals changes in activity also occurred on the sea floor. This coincidence suggests worldwide effects of movement of crustal plates. PMID- 17742852 TI - Ctenocystoidea: new class of primitive echinoderms. AB - The oldest known "carpoids" of the echinoderm subphylum Homalozoa have been discovered in lower Middle Cambrian rocks of northern Utah. They were free-living benthonic animals characterized by a unique ctenoid feeding apparatus and flattened flexible theca with near bilateral symmetry. A new class, Ctenocystoidea, is proposed to include the new genus and new species, Ctenocystis utahensis. PMID- 17742853 TI - Spherical urine in birds: petrography. AB - The white part of bird droppings (the urine) consists of microscopically uniform spheres 2 to 8 micrometers in diameter. Strange behavior of the spheres in polarized light indicates that they are often made of a spiraling arrangement of crystals that are particularly well revealed by the electron microscope. Bird urine has a varied composition, and x-ray analysis shows that it does not consist largely of uric acid, as has frequently been parroted. PMID- 17742854 TI - Physalia nematocysts: utilized by mollusks for defense. AB - Nudibranchs Glaucus and Glaucilla store and utilize for their own defense the nematocysts of the venomous siphonophore Physalia. PMID- 17742855 TI - Ecdysone analog: conversion to alpha ecdysone and 20-hydroxyecdysone by an insect. AB - The tritium-labeled synthetic ecdysone analog Delta(7)-5beta-cholestene-2beta, 3beta,14alpha-triol-6-one terminated diapause when injected into diapausing tobacco hornworm pupae and was converted into tritium-labeled alpha-ecdysone and tritium-labeled 20-hydroxyecdysone. About half of the crystalline alpha-ecdysone and 20-hydroxyecdysone isolated from the tobacco hornworms 7(1/2) to 8(1/2) days after injection was derived from endogenous steroid precursors and half from the transformation of the synthetic ecdysone analog. PMID- 17742856 TI - Neuronal network triggering a fixed action pattern. AB - Bursts of impulses in groups of brain cells of the nudibranch Tritonia trigger prolonged swimming that is identical to the natural escape response. The cells in which the activity occurs form two bilaterally symmetrical groups of at least 30 cells in each pleural ganglion. These neurons are interconnected by pathways that have a low electrical resistance, both within a ganglion and across the brain. Together they form a network that determinies whether a swimming escape response will occur or not by filtering out weak neural activity yet responding with a burst of impulses to intensive specific input to either group. PMID- 17742857 TI - Caribbean cores p6304-8 and p6304-9: new analysis of absolute chronology. A reply. PMID- 17742858 TI - Out of the ivory tower. PMID- 17742859 TI - AAAS Annual Meeting Television Coverage. PMID- 17742860 TI - PRELIMINARY ANNOUNCEMENT OF THE NEW YORK MEETING. PMID- 17742861 TI - WAR EMERGENCY COURSES IN THE UNIVERSITY. PMID- 17742862 TI - CHARLES L. MAYER AWARDS OF THE NATIONAL SCIENCE FUND. PMID- 17742863 TI - METEOROLOGICAL OFFICERS IN THE ARMY AIR FORCES. PMID- 17742864 TI - THE NUTRITION FOUNDATION. PMID- 17742865 TI - THE NATIONAL FOUNDATION FOR INFANTILE PARALYSIS. PMID- 17742867 TI - THE TOOLS OF SCIENCE AND THE WAR INDUSTRY. PMID- 17742866 TI - BACTERIAL GENERIC NAMES AS COMMON NOUNS. PMID- 17742868 TI - A METEORITE FROM VERMONT. PMID- 17742870 TI - THE PRESENCE OF A CORTIN-LIKE SUBSTANCE (COLD PROTECTING MATERIAL) IN THE URINE OF NORMAL MEN. PMID- 17742869 TI - ANOTHER MOULD WITH ANTI-BACTERIAL ABILITY. PMID- 17742871 TI - HAY FEVER AND VITAMIN C. PMID- 17742872 TI - A SIMPLIFIED PROCEDURE FOR THE CONCENTRATION AND PURIFICATION OF INFLUENZA VIRUS. PMID- 17742874 TI - National Academy: Public Policy Group, Headed by Kistiakowsky, Seems Bound for Important Role. PMID- 17742873 TI - The First Director. PMID- 17742875 TI - Foreign Aid: Latin-American Science Board Set Up To Help with Alliance for Progress. PMID- 17742876 TI - Congress: New Study Shows Federal Education Budget of $2.2 Billion, $613 Million of It for Research. PMID- 17742877 TI - World Atom Agency: Indian Reactor Accord, Agreement on Japan Point to More Significant Role for IAEA. PMID- 17742878 TI - Krebiozen: FDA Deadline Brings New, but Not the Final, Episode in Controversy over Cancer Drug. PMID- 17742880 TI - Tellurium: A New Sensitive Test. AB - A new, extremely sensitive method for the quantitative determination of tellurium is based on the induced precipitation of elemental gold from a 6N HCl solution containing gold chloride, cupric chloride, and hypophosphorous acid; the amount of gold reduced is proportional to the amount of tellurium present. As little as 1 nanogram (1 X 1O(-9) g) of tellurium gives a measurable reaction with 1 mg of gold in 50 ml of solution. PMID- 17742879 TI - Microtus: A Simple Method of Recording Time Spent in the Nest. AB - A prairie vole, Microtus ochrogaster, was tagged with a radioactive label, a survey meter was placed over its nest, and the presence or absence of the animal in the nest was recorded on tape. PMID- 17742881 TI - Thin Membranes of Parlodion. AB - Parlodion membranes 50 to 1000 A A thick have been prepared by deposition of isoamyl acetate solutions on the air-water interface under conditions of controlled evaporation. Capacitance and resistance measurements have established the integrity of large areas of these membranes. The former also provides corroboration of the thickness estimated from the amounts of parlodion deposited. PMID- 17742882 TI - "Apocatalase" of Catalase-Negative Staphylococci. AB - Crystalline catalase of high purity and activity was prepared from a heme requiring Staphylococcus aureus mutant, JT/52, grown in the presence of heme. A crystalline protein was obtained from the same cells grown without heme. This enzymatically inactive protein and the catalase cross-react strongly when tested by a variety of immunochemical tests. PMID- 17742883 TI - Calcium-Activated Adenosine Triphosphatase Localization in Cultured Beating Heart Cells. AB - The calcium-activated adenosine triphosphatase activity of cultured single beating heart cells of the rat was localized and visualized by incubating the cells, after extraction in a mixture of glycerol and water, with adenosine triphosphate and calcium. The calcium phosphate, precipitated at the site of the enzyme reaction, was converted into a visible precipitate. The enzyme activity appeared in bands perpendicular to the myofibrils. PMID- 17742884 TI - Underwater Sounds of Pinnipeds. AB - Descriptions and analyses are presented of underwater sounds made by six species of seals in captivity, Zalophus californianus, Phoca vitulina, P. (Pusa) hispida, P. (Pagophilus) groenlandica, Halichoerus grypus, and Cystophora cristata. The suitability of these very faint sounds for echolocation is discussed. PMID- 17742885 TI - Visual Reinforcement in Siamese Fighting Fish. AB - Male Siamese fighting fish (Betta splendens) were conditioned to emit an instrumental response to obtain the visual image of another male of the species. The relative positive reinforcing effects of three visual stimuli capable of eliciting aggressive display were compared. PMID- 17742886 TI - Fragment Sizes Produced from T5 Bacteriophage DNA Molecules by Acid Deoxyribonuclease. AB - The action of acid deoxyribonuclease on T5 bacteriophage DNA results in a "random distribution" of sizes of duplex fragments as judged by electron microscopy. No preferred subunit size resulting from the "single hit" action can be detected down to lengths of 0.1 micron or less. The results are in agreement with the coexistence of a "single-hit" and a "double-hit" kinetics. PMID- 17742887 TI - Noble Gas Compounds. PMID- 17742888 TI - Anticholinesterase Agents. PMID- 17742889 TI - Meeting Notes. PMID- 17742890 TI - Forthcoming Events. PMID- 17742891 TI - Popular Scientific Publications. PMID- 17742892 TI - Experimentation in Citizen Reaction? PMID- 17742893 TI - Periodic Table and the Formation of Inert Gas Molecules. PMID- 17742895 TI - THE INFLUENCE OF CHEMICAL THOUGHT ON BIOLOGY. PMID- 17742894 TI - Keeping up with Current Research: Science Information Exchange. PMID- 17742896 TI - FROM THE CORRESPONDENCE OF OLIVER WOLCOTT GIBBS. PMID- 17742897 TI - ORDOVICIAN FOSSILS FROM LABRADOR. PMID- 17742898 TI - THE ANNUAL SCIENCE EXHIBITION. PMID- 17742899 TI - OVUM AGE AND THE COURSE OF GESTATION IN THE GUINEA PIG. PMID- 17742900 TI - ETIOLOGY OF ULCERATIVE ENTERITIS IN UPLAND GAME BIRDS. PMID- 17742901 TI - THE BLOOD IN HEMOPHILIA. PMID- 17742902 TI - VINEGAR AS A SOIL DISINFECTANT. PMID- 17742903 TI - A METHOD FOR THE MEASUREMENT OF ACTIVITY OF SMALL ANIMALS. PMID- 17742904 TI - FORTY YEARS' FLUCTUATIONS IN MATHEMATICAL RESEARCH. PMID- 17742905 TI - NICHOLAI ALEXEYEVICH OUMOV. PMID- 17742906 TI - CLASSIFICATION OF TECHNICAL LITERATURE. PMID- 17742907 TI - THE NINETEENTH INTERNATIONAL CONGRESS OF AMERICANISTS. PMID- 17742908 TI - NOTE ON THE MERIDIONAL DEVIATION OF A FALLING BODY. PMID- 17742909 TI - VEGETATIVE REGENERATION OF ALFALFA. PMID- 17742910 TI - THE ORGANIZATION OF SCIENCE IN GREAT BRITAIN. PMID- 17742911 TI - ELECTRICAL DENSITY AND ABSORPTION OF beta-RAYS. PMID- 17742912 TI - EVIDENCE PROVING THAT THE BELLY RIVER BEDS OF ALBERTA ARE EQUIVALENT WITH THE JUDITH RIVER BEDS OF MONTANA. PMID- 17742913 TI - THE TRAVERTINE RECORD OF BLAKE SEA. PMID- 17742914 TI - Ediacaran fossils. PMID- 17742915 TI - Acetylene on titan. PMID- 17742916 TI - Acetylene on titan. PMID- 17742917 TI - Ediacaran fossils. PMID- 17742918 TI - Federal R & d budget: guns versus butter. PMID- 17742919 TI - Impact theory of mass extinctions and the invertebrate fossil record. AB - There is much evidence that the Cretaceous-Tertiary boundary was marked by a massive meteorite impact. Theoretical consideration of the consquences of such an impact predicts sharp extinctions in many groups of animals precisely at the boundary. Paleontological data clearly show gradual declines in diversity over the last 1 to 10 million years in various invertebrate groups.Reexamination of data from careful studies of the best sections shows that, in addition to undergoing the decline, four groups (ammonites, cheilostomate beyozoans, brachiopods, and bivalves) were affected by sudden truncations precisely at the iridium anomaly that marks the boundary. The paleontological record thus bears witness to terminal-Cretaceous extinctions on two time scales: a slow decline unrelated to the impact and a sharp truncation synchronous with and probably caused by the impact. PMID- 17742920 TI - Hydrogen-evolving solar cells. AB - Sunlight is directly converted to chemical energy in hydrogen-evolving photoelectrochemical cells with semiconductor electrodes. Their Gibbs free energy efficiency of solar-to-hydrogen conversion, 13.3 percent, exceeds the solar-to fuel conversion efficiency of green plants and approaches the solar-to-electrical conversion efficiency of the best p-n junction cells. In hydrogen-evolving photoelectrodes, electron-hole pairs photogenerated in the semiconductor are separated at electrical microcontacts between the semiconductor and group VIII metal catalyst islands. Conversion is efficient when the island diameters are small relative to the wave-lengths of sunlight exciting the semiconductor; when the island spacings are smaller than the diffusion length of electrons at the semiconductor surface; when the height of the potential energy barriers that separate the photogenerated electrons from holes at the semiconductor surface is raised by hydrogen alloying of the islands; when radiationless recombination of electron-hole pairs at the semiconductor-solution interface between the islands is suppressed by controlling the semiconductor surface chemistry; and when the semiconductor has an appropriate band gap (1.0 to 1.8 electron volts) for efficient solar conversion. PMID- 17742921 TI - Herbicide-resistant mutants from tobacco cell cultures. AB - Several mutants resistant to the herbicides chlorsulfuron and sulfometuron methyl were isolated form cultured cells of Nicotiana tabacum. Resistance was inherited as a single dominant or semidominant mutation in all cases. Linkage analysis of six mutants identified two unlinked genetic loci. Studies of plants homozygous for one mutation showed the mutant plants to be completely resistant to treatment with a concentration of chlorsulfuron 100 times higher than that which produces symptoms of phytotoxicity on normal plants. PMID- 17742922 TI - "Science Shops" Flourish in Europe: Organizations intent on focusing more university research on social problems have gained important political and financial support. PMID- 17742923 TI - Europeans back computer plan. PMID- 17742924 TI - Can Multibond Reactions Be Synchronous?: A maverick theoretician touches off a debate on both synchronicity and the relative efficacies of molecular orbital calculations. PMID- 17742925 TI - Computing Without Dissipating Energy: Computers are machines and should be subject to thermodynamics; what is the minimum energy needed for computation? PMID- 17742926 TI - AAAS Annual Meeting New York, 24-29 May 1984: Tours and Special Events. PMID- 17742927 TI - Solar physics: weather and climate responses to solar variations. PMID- 17742928 TI - Monopoles: magnetic monopoles. PMID- 17742930 TI - A maya site: coba. PMID- 17742929 TI - Tropical biology: costa rican natural history. PMID- 17742931 TI - End-cretaceous brachiopod extinctions in the chalk of denmark. AB - The results of a detailed study of the brachiopods of the most complete Cretaceous-Tertiary boundary in Denmark, Nye Klslashed circlev, show an extinction pattern for this marine invertebrate group compatible with that reported for pelagic foraminifera and coccoliths and with the impact scenario. The extinction is abrupt, coinciding with the Maastrichtian-Danian boundary. There is no warning in the form of decreasing density, decreasing diversity, or early extinction of specialized groups. The basal few meters of the Danian are almost devoid of brachiopods, and a Danian brachiopod fauna starts almost as abruptly as the Maastrichtian fauna disappeared. The new fauna is similar to the Maastrichtian as regards density and diversity, and at maximum six species are common to both stages. The northwest European Masstrichtian chalk is composed mainly of the remains of coccoliths and pelagic foraminifera. The mass extinction of these groups led to a total cessation of chalk production. The chalk is overlain by a thin clay bed deposited partly under anoxic conditions. This combination of anoxia and clay deposition coupled with a cessation of productivity led to the extinction of specialized groups such as the chalk brachiopods. The surviving species included forms that could survive in well aerated shallow marine waters on substrates other than chalk. PMID- 17742932 TI - Terminal cretaceous extinctions in the hell creek area, montana: compatible with catastrophic extinction. AB - Inaccurate stratigraphic correlations in the Hell Creek area, Montana, have led to the assumption that transitional vertebrate faunas (Bug Creek Anthills) exist in the latest Cretaceous, refuting a catastrophic turnover at the Cretaceous Tertiary boundary. Establishment of the transitional faunas in Paleocene channels that cut down through the Cretaceous-Tertiary boundary renders the terrestrial faunal record compatible with the marine record and with catastrophic extinction. PMID- 17742933 TI - Geologic framework of nonmarine cretaceous-tertiary boundary sites, raton basin, new Mexico and colorado. AB - Iridium concentrations are anomalously high at the palynological Cretaceous Tertiary boundary in fluvial sedimentary rocks of the lower part of the Raton Formation at several localities in the Raton Basin of New Mexico and Colorado. The iridium anomaly is associated with a thin bed of kaolinitic claystone in a discontinuous carbonaceous shale and coal sequence. PMID- 17742934 TI - The end of the cretaceous: sharp boundary or gradual transition? AB - Evidence indicates that the Cretaceous-Tertiary boundary is very sharp, and, within the limits of resolution, it is apparently synchronous at the various boundary localities. Arguments to the contrary, particularly those of Officer and Darke, are shown to invalid. PMID- 17742935 TI - Mass spawning in tropical reef corals. AB - Synchronous multispecific spawning by a total of 32 coral species occurred a few nights after late spring full moons in 1981 and 1982 at three locations on the Great Barrier Reef, Australia. The data invalidate the generalization that most corals have internally fertilized, brooded planula larvae. In every species observed, gametes were released; external fertilization and development then followed. The developmental rates of externally fertilized eggs and longevities of planulae indicate that planulae may be dispersed between reefs. PMID- 17742936 TI - Science advice for state governments. PMID- 17742937 TI - Abnormal Pressures in Deep Wells of Southwestern Louisiana: High fluid pressures are associated with slump-type faults and shed light on processes of compaction. PMID- 17742938 TI - Education for Management and Technology in the 1970's: The universities and business must foster entrepreneurship and its interaction with technology. AB - In summary, then, let me restate my conviction that the most critical needs of management in the next decade will be met by the identification and cultivation of the innovative, creative, adaptable individual who sets as his goal the translation of technology for society's needs. He will require a command of the growing body of managerial knowledge. He will need a continual refreshment of that knowledge through contact with the university as he seeks to deal with a world in change. If his firm is to encourage and use his creative capacity, it will be careful about his entry into the organization and his movement up the ladder, stressing only the values that count, that are pivotal, and taking care not to drive him into rebellion or conformity. The firm will be inventive about ways to give him opportunities to test his ideas. It will experiment with organizational forms which promote creativity. It will encourage adventure and accept risk. And in its success, it will be serving the needs of our societies in ways that will make our greatest hopes for technology a full and human reality. PMID- 17742940 TI - Visa refused for French critic of u.s. PMID- 17742939 TI - Du Pont and Delaware: Academic Life behind the Nylon Curtain. PMID- 17742942 TI - NSF Budget: House Committee Votes $100-Million Cut. PMID- 17742944 TI - This week in science. PMID- 17742943 TI - Space Budget: Down 20 Percent in 1 Year--at Least. PMID- 17742945 TI - Science and restoration. PMID- 17742946 TI - Corrections and clarifications. AB - The title of the Perspective by Christopher Miller in the issue of 24 September (p. 1692) was printed incorrectly. It should have read, "Potassium selectivity in proteins: Oxygen cage or pi in the face?" In the figure caption on the same page, "-electron" was printed incorrectly instead of "pi-electron." PMID- 17742947 TI - The chlorine controversy. PMID- 17742948 TI - Sciencescope. PMID- 17742949 TI - National science, technology medalists. PMID- 17742950 TI - Young scientists' network shakes up the establishment. PMID- 17742951 TI - Pleistocene population explosions. PMID- 17742953 TI - High-tc superconductors get squeezed. PMID- 17742952 TI - Are dark stars the silent majority? PMID- 17742955 TI - Keeping score on animal activism. PMID- 17742954 TI - Galileo reveals a badly battered ida. PMID- 17742956 TI - Research reactors dodge a bullet. PMID- 17742957 TI - Hominid sites ravaged by homo sapiens. PMID- 17742958 TI - NIGMS to Go Out On a Limb. PMID- 17742959 TI - A map for mankind. PMID- 17742960 TI - Lasker awards resume. PMID- 17742961 TI - Apple Growers vs. CBS: TV Wins. PMID- 17742962 TI - Inclined-Field Structure, Morphology, and Pinning of the Vortex Lattice in Microtwinned YBa2Cu3O7. AB - A detailed small-angle neutron scattering study of the vortex lattice in a single crystal of YBa(2)Cu(3)O(7) was made for a field of 0.5 tesla inclined at angles between 0 and 80 degrees to the crystalline c axis. The vortex lattice is triangular for all angles, and for angles less than or equal to 70 degrees its orientation adjusts itself to maximize the pinning energy to densely and highly regularly spaced twin planes. These observations have important implications for the microscopic flux-pinning mechanism, and hence for the critical current achievable in YBa(2)Cu(3)O(7). For large angles (about 80 degrees) the vortex lattice consists of independent chains in the orientation predicted by anisotropic London theory. PMID- 17742963 TI - Anatomy of the photodissociation region in the orion bar. AB - Much of the interstellar gas resides in photodissociation regions whose chemistry and energy balance is controlled by the flux of far-ultraviolet radiation upon them. These photons can ionize and dissociate molecules and heat the gas through the photoelectric effect working on dust grains. These regions have been extensively modeled theoretically, but detailed observational studies are few. Mapping of the prominent Orion Bar photodissociation region at wavelengths corresponding to the carbon-hydrogen stretching mode of polycyclic aromatic hydrocarbons, the 1-0 S(1) line of molecular hydrogen, and the J = 1-0 rotational line of carbon monoxide allows the penetration of the far-ultraviolet radiation into the cloud to be traced. The results strongly support the theoretical models and show conclusively that the incident far-ultraviolet radiation field, not shocks as has sometimes been proposed, is responsible for the emission in the Orion Bar. PMID- 17742964 TI - Early cambrian ostracode larvae with a univalved carapace. AB - Phosphatized univalves, recovered from the Lower Cambrian ( approximately 530 million years old) Qiongzhusi Formation in southern China, are recognized as early instars belonging to bradoriid ostracodes whose later instars are bivalved. The univalved form is the primitive larval character for shell-secreting crustaceans, although most post-Cambrian ostracodes bypassed this developmental phase. The univalved-bivalved transition during early on-togeny represents an important evolutionary event in ostracodes, with implications for crustacean classification, and implies that the ostracode ancestor achieved this bivalved capacity before the appearance of mineralized skeletons during the "Cambrian explosion." PMID- 17742965 TI - Deep and Bottom Water of the Weddell Sea's Western Rim. AB - Oceanographic observations from the Ice Station Weddell 1 show that the western rim of the Weddell Gyre contributes to Weddell Sea Bottom Water. A thin (< 300 meters), highly oxygenated benthic layer is composed of a low-salinity type of bottom water overlying a high-salinity component. This complex layering disappears near 66 degrees S because of vertical mixing and further inflow from the continental margin. The bottom water flowing out of the western rim is a blend of the two types. Additionally, the data show that a narrow band of warmer Weddell Deep Water hugged the continental margin as it flowed into the western rim, providing the continental margin with the salt required for bottom-water production. PMID- 17742967 TI - Hot neologisms. PMID- 17742966 TI - Pressure-induced enhancement of tc above 150 k in hg-1223. AB - The recently discovered homologous series HgBa(2)Can-1 Cun O2n+2+delta possesses remarkable properties. A superconducting transition temperature, T(c), as high as 133 kelvin has been measured in a multiphase Hg-Ba-Ca-Cu-O sample and found to be attributable to the Hg-1223 compound. Temperature-dependent electrical resistivity measurements under pressure on a (> 95%) pure Hg-1223 phase are reported. These data show that T(c) increases steadily with pressure at a rate of about 1 kelvin per gigapascal up to 15 gigapascals, then more slowly and reaches a T(c) = 150 kelvin, with the onset of the transition at 157 kelvin, for 23.5 gigapascals. This large pressure variation (as compared to the small effects observed in similar compounds with the optimal T(c)) strongly suggests that higher critical temperatures could be obtained at atmospheric pressure. PMID- 17742968 TI - Post-gradualism. PMID- 17742969 TI - Vignette: the nobel. PMID- 17742970 TI - The birth of stars. PMID- 17742971 TI - Other books of interest. PMID- 17742972 TI - Worthy animals. PMID- 17742973 TI - Products & materials. PMID- 17742974 TI - THE NEW OPPORTUNITY IN SCIENCE. PMID- 17742975 TI - CHEMISTRY IN THE NAVY. PMID- 17742977 TI - INSTINCTIVE BEHAVIOR IN THE WHITE RAT. PMID- 17742978 TI - AN EARLIER SNOW EFFECT. PMID- 17742976 TI - BIRTHS AND DEATHS IN THE CIVIL POPULATION OF FRANCE IN THE WAR-TIME. PMID- 17742980 TI - COMPLETE REVERSAL OF SEX IN HEMP. PMID- 17742981 TI - THE GERMPLASM AS A STEREOCHEMIC SYSTEM. PMID- 17742979 TI - THE PROGRESS OF UNDERGRADUATE RESEARCH IN MEDICAL SCHOOLS. PMID- 17742983 TI - METHODS OF RESUSCITATION. PMID- 17742982 TI - THE CONTENT AND STRUCTURE OF THE ATOM. PMID- 17742984 TI - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES. PMID- 17742985 TI - AWARDS OF THE JOHN SCOTT MEDAL. PMID- 17742986 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17742987 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17742988 TI - THE HISTORY OF SCIENCE. PMID- 17742990 TI - CHEMISTRY IN THE AGRICULTURAL COLLEGE. PMID- 17742989 TI - THE RENOUNCING OF HONORARY DEGREES. PMID- 17742991 TI - THE ANNTIVERSARY OF A GREAT GARDEN. PMID- 17742993 TI - ON THE FEASIBILITY OF DETERMINING EXPERIMENTALLY THE LUNAR AND SOLAR DEFLECTION OF THE VERTICAL BY MEANS OF TWO CONNECTED WATER TANKS. PMID- 17742994 TI - APPROXIMATE MEASUREMENT OF TEXTILE FIBERS. PMID- 17742992 TI - ACTIVATION OF THE UNFERTILIZED EGG BY ULTRA-VIOLET RAYS. PMID- 17742997 TI - "LODI MAN". PMID- 17742995 TI - SURFACE MOTION OF WATER INDUCED BY WIND. PMID- 17742996 TI - SOME UNSOLVED PROBLEMS IN HUMAN ADJUSTMENT. PMID- 17742998 TI - A NEW DISTURBANCE OF RED PINE. PMID- 17742999 TI - LUTHER BURBANK. PMID- 17743000 TI - SELENIUM DEHYDROGENATION OF NAPELLINE. PMID- 17743001 TI - THE REINSTATEMENT OF PROFESSOR SCHAPER. PMID- 17743002 TI - THE TREATMENT OF CANINE DISTEMPER WITH A CHEMOTHERAPEUTIC AGENT, SODIUM SULFANILYL SULFANILATE. PMID- 17743003 TI - THE LIQUEFACTION OF SPONTANEOUS TUMORS OF THE MAMMARY GLAND IN MICE BY HEPTYL ALDEHYDE. PMID- 17743004 TI - THE EFFECT OF LIGATION OF THE LUMBOADRENAL VEINS ON THE COURSE OF EXPERIMENTAL DIABETES IN DOGS AND CATS. PMID- 17743006 TI - A USEFUL METHOD FOR MOUNTING INSECTS. PMID- 17743005 TI - CLEAVING NEMATODE EGGS AS RESEARCH AND CLASSROOM MATERIAL. PMID- 17743007 TI - SCIENCE NEWS. PMID- 17743008 TI - THE BIOLOGICALLY MINDED PHYSICIAN. PMID- 17743009 TI - A NEW HOUSEHOLD PALM, NEANTHE BELLA. PMID- 17743011 TI - "RACES" AND "HOMING" OF PACIFIC SALMON. PMID- 17743010 TI - THE FISH BOWL AS A FIRE HAZARD. PMID- 17743012 TI - A POSSIBLE SOURCE OF LABORATORY FIRES. PMID- 17743013 TI - TUMOR PRODUCTION BY HORMONES FROM PHYTOMONAS TUMEFACIENS. PMID- 17743014 TI - SALT ACCUMULATION AND POLAR TRANSPORT OF PLANT HORMONES. PMID- 17743015 TI - THE EFFECT OF REPEATED CORTIN INJECTIONS UPON RENAL EXCRETION IN THE NORMAL ORGANISM. PMID- 17743016 TI - THE GREEN MUSCARDINE FUNGUS ON THE PERIODICAL CICADA. PMID- 17743018 TI - THE USE OF DIALYSIS IN THE PREPARATION AND PURIFICATION OF IMMUNOLOGICALLY ACTIVE BACTERIAL PRODUCTS. PMID- 17743017 TI - A PLEURAL CANNULA. PMID- 17743019 TI - This week in science. PMID- 17743020 TI - Response. PMID- 17743021 TI - Corrections and clarifications. AB - In the news briefing "The world's most prolific scientists" (17 Jan., p. 283), Arnold L. Rheingold, a crystallographer at the University of Delaware, was inadvertently left off the list of the top 20 most prolific scientists. The Institute for Scientific Information has corrected its list and states that Rheingold published 391 articles and other scientific communications between 1981 and the end of 1990. He should have ranked 13th on the list. PMID- 17743022 TI - Response. PMID- 17743023 TI - Sciencescope. PMID- 17743024 TI - U.s. And Russia proceed cautiously. PMID- 17743025 TI - Astronomers bag another black hole. PMID- 17743027 TI - ...Pats on the back for science. PMID- 17743026 TI - Galileo Gets a Boost; UARS Goes Bust. PMID- 17743028 TI - Awards in biomedicine.. PMID- 17743029 TI - Scientific minority- and womanpower. PMID- 17743030 TI - The worm turned out. PMID- 17743031 TI - Less laissez-faire in French gene-splicing? PMID- 17743032 TI - Paleoclimatic signature in terrestrial flood deposits. AB - Large-scale process simulation was used to reconstruct the geologic evolution during the past 600,000 years of an alluvial fan in northern California. In order to reproduce the sedimentary record, the simulation accounted for the dynamics of river flooding, sedimentation, subsidence, land movement that resulted from faulting, and sea level changes. Paleoclimatic trends induced fluctuations in stream flows and dominated the development of the sedimentary deposits. The process simulation approach serves as a quantitative means to explore the genesis of sedimentary architecture and its link to past climatic conditions and fault motion. PMID- 17743033 TI - Luminescent color image generation on porous silicon. AB - Black and white images were projected onto n-type silicon (100) wafers during a photoelectrochemical etch to produce a color image that photoluminesces. The photoluminescence originates from a thin layer of luminescent porous silicon that is produced in the photoetch, and the colors that appear in the etched image arise from thin-film optical interference. A diffraction grating was also photoetched into the substrate, demonstrating simultaneous encoding of a gray scale image into thin-film interference, luminescence, and diffraction phenomena. PMID- 17743034 TI - Energetics of large fullerenes: balls, tubes, and capsules. AB - First-principles calculations were performed to compare the energies of 29 different fullerene structures, with mass number from 60 to 240, and of eight nonhelical graphite tubes of different radii. A quantity called the planarity, which indicates the completeness of the pi-bonding, is the single most important parameter determining the energetics of these structures. Empirical equations were constructed for the energies of nonhelical tubes and for those fullerene structures that may be described as balls or capsules. For a given mass number, bail-shaped fullerenes are energetically favored over capsular (tube-like) fullerenes. PMID- 17743037 TI - Autonomic advances. PMID- 17743036 TI - Response. PMID- 17743038 TI - Low-energy particle physics. PMID- 17743039 TI - Developments in vision. PMID- 17743040 TI - Vignettes: nature stories. PMID- 17743041 TI - Beetle model. PMID- 17743042 TI - Products & materials. PMID- 17743043 TI - A Favorable Environment for Research. PMID- 17743044 TI - Evolutionary Mechanisms in Pollination Biology: Origins and functions of floral systems are being elucidated by genetical and ecological studies. PMID- 17743045 TI - Are We Retrogressing in Science?: Despite superficial evidence to the contrary, science in the United States is in a state of confusion. AB - Despite the large amount of superficial evidence to the contrary, the present state of science in the United States is one of considerable confusion. In large measure, we appear to have lost sight of our intellectual foundations and to have reverted to authoritarianism. Contributing to this situation is the state of the universities. Since World War II these have become so deeply engaged in the pursuit of various kinds of applied research that they have seriously neglected their primary duties as institutions of learning and of education. Possibly the greatest source of this disruption is the government contract-grant system upon which the universities are becoming increasingly dependent for continued existence. PMID- 17743046 TI - Space Program: Skepticism Grows But in Context of Cold War It Is Hard for Congress To Say No. PMID- 17743047 TI - Fish Flour: Administration's Interest Has Not Been Matched by Funds for Needed Research. PMID- 17743048 TI - Electron Microscopes: Committee in House Urges Reinstatement of Former Tariff on Foreign Models. PMID- 17743049 TI - The Manhunters: British Minister Blames American Recruiters for Emigration of Scientists. PMID- 17743050 TI - Charged Particles. AB - There was a complete absence of charged particles associated with the planet Venus at radial distances as small as 41,000 km on the sunward side of the planet. This result is taken to mean that the magnetosphere of Venus, if any, does not extend to that great a distance. The most plausible interpretation is that (MV/ME) /=10 electron volts (for example, oxygen, neon, and sulfur) by factors of 3 to 10 with respect to the photosphere. The origin of this FIP effect is unknown. The launch of the Extreme Ultraviolet Explorer Satellite (EUVE) opened up the spectroscopic capability required to determine elemental abundances in the coronae of other stars. Spectroscopic observations of the corona of the nearby F5 IV star Procyon obtained with EUVE have yielded estimates of the relative abundances of high- and low-FIP species. The results provide evidence that Procyon, unlike the sun, does not exhibit the FIP effect. Whether the sun or Procyon is more typical of the general late-type stellar population is of fundamental interest to the physics of stellar outer atmospheres and has a bearing on the origin of cosmic rays. PMID- 17743545 TI - Conducting Layered Organic-inorganic Halides Containing <110>-Oriented Perovskite Sheets. AB - Single crystals of the layered organic-inorganic perovskites, [NH(2)C(I=NH(2)](2)(CH(3)NH(3))m SnmI3m+2, were prepared by an aqueous solution growth technique. In contrast to the recently discovered family, (C(4)H(9)NH(3))(2)(CH(3)NH(3))n-1SnnI3n+1, which consists of (100)-terminated perovskite layers, structure determination reveals an unusual structural class with sets of m <110>-oriented CH(3)NH(3)SnI(3) perovskite sheets separated by iodoformamidinium cations. Whereas the m = 2 compound is semiconducting with a band gap of 0.33 +/- 0.05 electron volt, increasing m leads to more metallic character. The ability to control perovskite sheet orientation through the choice of organic cation demonstrates the flexibility provided by organic-inorganic perovskites and adds an important handle for tailoring and understanding lower dimensional transport in layered perovskites. PMID- 17743546 TI - A "Double-Diamond Superlattice" Built Up of Cd17S4(SCH2CH2OH)26 Clusters. AB - A simple preparation of Cd(17)S(4)(SCH(2)CH(2)OH)(26) clusters in aqueous solution leads to the formation of colorless blocky crystals. X-ray structure determinations revealed a superlattice framework built up of covalently linked clusters. This superlattice is best described as two enlarged and interlaced diamond or zinc blende lattices. Because both the superlattice and the clusters display the same structural features, the crystal structure resembles the self similarities known from fractal geometry. The optical spectrum of the cluster solution displays a sharp transition around 290 nanometers with a large absorption coefficient ( approximately 84,000 per molar per centimeter). PMID- 17743547 TI - Micrometer- and nanometer-sized polymeric light-emitting diodes. AB - A method for the fabrication of micrometer-and submicrometer-sized polymeric light-emitting diodes is presented. Such diodes have a variety of applications. Light sources of dimensions around 100 nanometers are required for subwavelength, near-field optical microscopy. Another possible application is patterning on the micrometer and nanometer scale. The diodes have been made in the form of a sandwich structure, with the conductive polymer poly(3,4-ethylene-dioxythiophene) polymerized in the pores of commercially available microfiltration membranes defining the hole-injecting contacts, poly[3-(4-octylphenyl)-2,2;-bithiophene] as the light-emitting layer, and a thin film of calcium-aluminum as the electron injector. PMID- 17743548 TI - Influence of lunar phase on daily global temperatures. AB - A newly available data set of daily satellite-derived, lower-tropospheric global temperature anomalies provides an opportunity to assess the influence of lunar phase on planetary temperature. These results reveal a statistically significant 0.02 K modulation between new moon and full moon, with the warmest daily global temperatures over a synodic month coincident with the occurrence of the full moon. Spectral analysis of the daily temperature record confirms the presence of a periodicity that matches the lunar synodic (29.53-day) cycle. The precision of the satellite-based daily temperature record allows verification that the moon exerts a discernible influence on the short-term, global temperature record. PMID- 17743549 TI - Conformation of macromolecules in the gas phase: use of matrix-assisted laser desorption methods in ion chromatography. AB - Conformational data for macromolecules in the gas phase have been obtained by the coupling of a matrix-assisted laser desorption ion source to an ion chromatograph. A series of polyethylene glycol (PEG) polymers "cationized" (converted to a cation) by sodium ions (Na(+)PEG9 to Na(+)PEG19) and a protonated neurotransmitter protein, bradykinin, were studied. Mobilities of Na(+)PEG9 to Na(+)PEG19 are reported. Detailed modeling of Na(+)PEG9 with molecular mechanics methods indicates that the lowest energy structure has the Na(+) ion "solvated" by the polymer chain with seven oxygen atoms as nearest neighbors. The agreement between the model and experiment is within 1 percent for Na(+)PEG9, Na(+)PEG13, and Na(+)PEG17, giving strong support to both the method and the deduced structures. Similar agreement was obtained in initial studies that modeled experimental data for arginine-protonated bradykinin. PMID- 17743550 TI - Patterns of peopling. PMID- 17743552 TI - Vignettes: comestibles. PMID- 17743551 TI - Workings of HIV. PMID- 17743554 TI - This week in science. PMID- 17743553 TI - Products & materials. PMID- 17743555 TI - A time for steadiness. PMID- 17743556 TI - Erratum. AB - In the Research News article "Why dynamiting vampire bats is wrong" by Roger Lewin (4 Apr., p. 24), Gordon Orians' name was spelled incorrectly. PMID- 17743557 TI - Overhead costs on research grants. PMID- 17743558 TI - Defining risk. PMID- 17743561 TI - Fill the Oil Reserve, Academy Report Says: While it saves money, the Administration's work stoppage at the reserve misses a chance to prepare for the 1990's. PMID- 17743559 TI - Punctuated equilibrium: empirical response. PMID- 17743560 TI - Bloch Prepares NSF for Lean Years: He is conducting a major planning effort to set priorities and free funds for fresh initiatives--whatever the Gramm-Rudman era holds. PMID- 17743562 TI - Pentagon's R&D Chief Roils the Waters: With some unconventional views, Donald Hicks sows controversy as he defends a $42-billion research budget. PMID- 17743563 TI - Hicks Attacks SDI Critics. PMID- 17743564 TI - Packard panel urges reforms. PMID- 17743565 TI - European commission proposes shift in joint research. PMID- 17743566 TI - Smithsonian photobiology lab to close. PMID- 17743567 TI - Mountain goat horn: a clue to extinction? PMID- 17743568 TI - Consensus on Silicon Surface Structure Near: Experiment and theory support a recent Japanese model of the elusive structure of a clean silicon surface, thereby bringing a journey of a quarter century close to its end. PMID- 17743569 TI - STM Evidence for Silicon (111). PMID- 17743570 TI - Sex differences in economic well-being. AB - Despite large structural changes in the economy and major antidiscrimination legislation, the economic well-being of women in comparison with that of men did not improve between 1959 and 1983. The women to men ratio of money income almost doubled, but women had less leisure while men had more, an increase in the proportion of adults not married made more women dependent on their own income, and women's share of financial responsibility for children rose. The net result for women's access to goods, services, and leisure in comparison with that of men ranged from a decrease of 15 percent to an increase of 4 percent, depending on assumptions about income sharing within households. PMID- 17743571 TI - Diamonds and the african lithosphere. AB - Data and inferences drawn from studies of diamond inclusions, xenocrysts, and xenoliths in the kimberlites of southern Africa are combined to characterize the structure of that portion of the Kaapvaal craton that lies within the mantle. The craton has a root composed in large part of peridotites that are strongly depleted in basaltic components. The asthenosphere boundary shelves from depths of 170 to 190 kilometers beneath the craton to approximately 140 kilometers beneath the mobile belts bordering the craton on the south and west. The root formed earlier than 3 billion years ago, and at that time ambient temperatures in it were 900 degrees to 1200 degrees C; these temperatures are near those estimated from data for xenoliths erupted in the Late Cretaceous or from present day heat-flow measurements. Many of the diamonds in southern Africa are believed to have crystallized in this root in Archean time and were xenocrysts in the kimberlites that brought them to the surface. PMID- 17743573 TI - Ramifications of genetics: in the name of eugenics. PMID- 17743572 TI - De Gustibus Non Est Disputandem: A Spiral Center for Taste in the Brain of the Teleost Fish, Heterotis niloticus. AB - The teleost fish, Heterotis niloticus, has elaborate paired, spiraled pharyngeal structures that aid in concentrating and swallowing food. These epibranchial organs are lined by an epithelium rich in taste buds. Both the taste buds and the muscles of the epibranchial organs are innervated by components of the vagal nerve. Horseradish peroxidase neuronal tracing experiments show that these nerve fibers are connected centrally to an enormous epibranchial portion of the vagal lobes-a special visceral sensory and motor region of the medulla. The epibranchial portion of the vagal lobe is among the most remarkable structures found in the brains of vertebrates, for it is itself a spiral. PMID- 17743574 TI - A transmutation in physics: from maxwell to microphysics. PMID- 17743575 TI - Herpetology in the pacific: biology of australasian frogs and reptiles. PMID- 17743576 TI - Papers from khabarovsk: beringia in the cenozoic era. PMID- 17743577 TI - Reprints of books previously reviewed. PMID- 17743578 TI - Products & materials. PMID- 17743579 TI - Agricultural research. PMID- 17743580 TI - Reversibility of psychiatric diagnoses. PMID- 17743581 TI - The fudge factor. PMID- 17743582 TI - The born-einstein letters. PMID- 17743583 TI - The laboratory frog. PMID- 17743584 TI - Thunderstorm activity. PMID- 17743585 TI - Effects of marijuana use. PMID- 17743586 TI - Trans-science and responsibility. PMID- 17743587 TI - Psychosurgery. PMID- 17743588 TI - Source of PCB's. PMID- 17743589 TI - Importation of petroleum. PMID- 17743591 TI - Science in Mexico (I): the revolution seeks a new ally. PMID- 17743590 TI - Unexpected symmetries in the "world knot". PMID- 17743592 TI - Computer for watergate probe. PMID- 17743593 TI - Energy: shortages loom, but conservation lags. PMID- 17743594 TI - Marston Warns of Threat to NIH. AB - A direct sense of alarm for the future of the National Institutes of Health is evident in the farewell speech of former director Robert Q. Marston. Associates of Marston, who was abruptly dismissed this January, say he was told by the White House that the decision was for neither personal nor institutional reasons. Others have suggested that Marston was dismissed simply because he was appointed by a Democratic Administration. However this may be, Marston's valedictory, delivered on 27 April, is concerned not about his own situation, but that of the NIH. PMID- 17743595 TI - Watergate fallout: administration quakes, science sneezes. PMID- 17743596 TI - Jaffe to leave drug office. PMID- 17743597 TI - Influenza (II): A Persistent Disease May Yield to New Vaccines. PMID- 17743598 TI - Gravity waves: correlation with geomagnetic storms. PMID- 17743599 TI - Water vapor from a lunar breccia: implications for evolving planetary atmospheres. AB - The exposure of a typical complex lunar breccia to hydrogen after a thorough outgassing produces a fully reduced surface state. Subsequent outgassing over a wide temperature range results in the production of water vapor formed from the chemisorbed hydrogen and oxygen from the lunar sample; the proposed mechanism has been confirmed in terms of the chemisorption of deuterium and the release of heavy water. Since the conditions of the experiments are consistent with those on the lunar surface, it is postulated that water vapor will be produced on the moon through the interaction of the solar wind with lunar soil. It is also proposed that such a process could play an important role in the early history of many planets where an oxygen-rich soil is exposed to a reducing atmosphere. PMID- 17743600 TI - Polarization: a key to an airbone optical system for the detection of oil on water. AB - Skylight polarization, which varies with the position of the sun in the sky, influences the contrast of oil on water. Good contrast is most consistently obtained by viewing in azimuth directions toward or away from the sun. Contrast is enhanced by imaging selected polarization components and by taking the difference between orthogonal polarization components. PMID- 17743601 TI - Horizontal bands in the belousov reaction. AB - The formation and propagation of spatial patterns in the presence of an initial gradient in temperature or the concentration of one or more of the reactants is explained kinematically. Experimental verification of this mechanism is given, showing that diffusion plays a very minor role in the formation of the bands. PMID- 17743602 TI - Al-khwarizmi: a new-found basin on the lunar far side. AB - Apollo 16 and Apollo 17 photographs of the far side of the moon reveal a double ringed basin 500 kilometers in diameter centered at 1 degrees N, 112 degrees E. The structure is very old and subdued; it is probably Pre-Nectarian in age and appears to have been filled and modified by younger events. The heights of the basin's rings are based on laser altimeter data from Apollo missions 15 through 17; these data suggest a third outer ring, approximately 1000 kilometers in diameter. Laser measurements also indicate that the filled basin separates the relatively low terrain on the eastern limb of the moon from the higher, more rugged highlands to the east. PMID- 17743603 TI - Remote radar sensing: atmospheric structure and insects. AB - A high-resolution radar sounder has been used in the simultaneous detection of atmospheric structure and insects. The vertical distribution of insects was often correlated with atmospheric structure. Continuous recordings revealed diurnal fluctuations and layering of insects at various altitudes. PMID- 17743604 TI - Hormonal control of sexual morphogenesis in achlya: dependence on protein and ribonucleic Acid syntheses. AB - The induction of the male sexual organ primordia (antheridial hyphae) by the steroid hormone antheridiol in the water mold Achlya ambisexualis requires both transcription and translation. Inhibition of either of these processes eliminates the expected increase in the production and release of the enzyme cellulase, which accompanies the formation of the antheridial hyphae. PMID- 17743605 TI - Photoalteration of pesticides: summary of workshop. PMID- 17743606 TI - Electrophysiological Evidence that Abnormal Early Visual Experience Can Modify the Human Brain. AB - In the caption of the cover photograph for 25 May 1973, the word "below" is misplaced; it should be deleted from the first sentence, and the second sentence should read: "(Below) Same view taken through a cylindrical lens . . ." Two errors occurred in the report by Freeman and Thibos in the same issue, p. 876: in column 2, line 4, "Freeman and co-workers" should be changed to "Freeman et al." in column 3, line 44, "the visual resolution" should be changed to "visual resolution"-Ed. PMID- 17743607 TI - THE EXPANDING RELATIONS OF CHEMISTRY IN AMERICA. PMID- 17743608 TI - ON THE ANALYSIS OF LIVING MATTER THROUGH ITS REACTIONS TO POISONS. PMID- 17743609 TI - FIELD MEETINGS OF THE ASSOCIATION OF AMERICAN STATE GEOLOGISTS. PMID- 17743610 TI - THE NEWCASTLE MEETING OF THE BRITISH ASSOCIATION. PMID- 17743611 TI - ATMOSPHERIC TRANSMISSION. PMID- 17743612 TI - A REMARKABLE AURORAL DISPLAY. PMID- 17743613 TI - INCREASING DEPTH OF FOCUS WITH THE SWING-BACK. PMID- 17743614 TI - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES. PMID- 17743615 TI - IMBIBITIONAL SWELLING OF PLANTS AND COLLOIDAL MIXTURES. PMID- 17743617 TI - Bad science and good policy analysis. PMID- 17743616 TI - THE THEORY OF AUTONOMOUS FOLDING IN EMBRYOGENESIS. PMID- 17743618 TI - Quark catalysis of exothermal nuclear reactions. AB - This article discusses circumstances under which free quarks catalyze exothermal nuclear reactions. It also presents possible methods for removing quarks sequestered by nuclear reaction products. Stable quarks that are negatively charged and significantly heavier than electrons attract positively charged nuclei to form new states of matter. The nuclei and quarks are closely bound, and presumably interact through both electromagnetic and nuclear forces. Nuclear fusion and fission are possible, as well as a new class of plural reactions in which either a quark isobar, isotope, or isotone is created in each individual reaction, with catalysis resulting in the overall system because the net transfer of charge, neutrons, or protons to the quarks is zero. The quark with quantum numbers of uu is a promising catalytic candidate. A satisfactory understanding of which reactions are or are not possible awaits the isolation of free quarks and a description of their strong interactions with matter. Finally, other kinds of stable negatively charged particles (such as heavy leptons), if discovered, can catalyze deuterium fusion reactions if thermal neutrons are used to liberate He(3)-bound catalytic particles. PMID- 17743619 TI - Nothomyrmecia macrops: A Living-Fossil Ant Rediscovered. AB - The Australian Nothomyrmecia macrops is the most primitive living ant. Until recently rediscovered, it was known only from two 46-year-old specimens, both workers. All developmental stages and adult castes are now known. Adults have stridulatory organs placed ventrally, between abdominal sternites III (with plectrum) and IV (with stridulitrum), differing from all other Hymenoptera, where these organs are dorsal. The chromosome number is the highest recorded for Hymenoptera (2n = 92). Virgin queens are brachypterous. Other anatomical and behavioral features are reviewed. Most are primitive for ants, many being shared with Myrmecia, another primitive Australian genus. Fundamental differences in abdominal structure place Myrmecia near the base of the poneroid phylad of ant subfamilies, while Nothomyrmecia is a primitive formicoid. PMID- 17743620 TI - Operating a major electric utility today. PMID- 17743621 TI - Investigators agree N.y. Blackout of 1977 could have been avoided. PMID- 17743622 TI - Alaska lands: senate panel tilts more toward development. PMID- 17743623 TI - Water projects: president facing a defiant congress. PMID- 17743624 TI - Environmental Lobbyists Quarrel over Endangered Species Act. PMID- 17743625 TI - Carter reorganization panel says federal data processing is lagging. PMID- 17743627 TI - AAAS Annual National Meeting: Houston. PMID- 17743626 TI - U.s. Earthquake hazards: real but uncertain in the East. PMID- 17743628 TI - On the delineation of social change. PMID- 17743629 TI - A mesoamerican culture. PMID- 17743630 TI - Axonal conduction processes. PMID- 17743631 TI - Venus: further evidence of vortex circulation. AB - A space-time composite of polar stereographic ultraviolet images of Venus from Mariner 10 shows a remarkable circumpolar vortex. The vortex is characterized by a cloud which appears similar to dense terrestrial stratus having an albedo that is 50 percent higher. Spiral streaks converge into it from low latitudes, akin to the spiral bands of a hurricane. The bright visible polar cloud is not axisymmetric but has roughly an elliptical shape. The high brightness of the polar cloud suggests that it has a different origin from the rest of the Venus cloud cover. PMID- 17743632 TI - Isoleucine epimerization in peptides and proteins: kinetic factors and application to fossil proteins. AB - The observed rate of isoleucine epimerization in peptides and proteins is dependent on (in addition to time and temperature) (i) the position of isoleucine in the peptide chain, (ii) the nature of adjacent amino acids, and (iii) the stability of the isoleucine peptide bonds. The relative rate is: NH(2)-terminal > COOH-terminal >> interior >/= free amino acid. The gradual hydrolysis of peptides and proteins to the more slowly epimerizing free amino acid causes a decrease in the apparent first-order rate constant with time. These results explain the isoleucine kinetics observed in fossil shells. PMID- 17743633 TI - Inland ice sheet thinning due to holocene warmth. AB - The climatic warming of 10,000 years ago is now affecting the central portions of ice sheets, causing ice-flow acceleration. This process explains the present-day thinning of the ice sheet in West Antarctica. Former ice sheets must have also responded to climatic warming with a delay of thousands of years. This lag in response is important in the climatic interpretation of glacial deposits and of changes in ice volume obtained from deep-sea cores. PMID- 17743634 TI - Oceanic Residence Times of Dissolved Beryllium and Aluminum Deduced from Cosmogenic Tracers 10Be and 26Al. AB - The residence times of the soluble fractions of beryllium and aluminum in seawater are estimated to be 1500 years or more. These residence times are estimated from a comparison of the annual deposition rates of cosmogenic beryllium-10 and aluminum-26 with the concentrations of beryllium-10 and aluminum 26 in seawater estimated from the specific activities of these radionuclides in an authigenic mineral assembly such as a manganese nodule. These residence times are greater by an order of magnitude than the mean residence times of beryllium and aluminum estimated from the geochemical balance. PMID- 17743635 TI - Bees have magnetic remanence. AB - Honey bees orient to the earth's magnetic field. This ability may be associated with a region of transversely oriented magnetic material in the front of the abdomen. The magnetic moment apparently develops in the pupal state and persists in the adults. PMID- 17743636 TI - Competitive interactions between neotropical pollinators and africanized honey bees. AB - The Africanized honey bee, a hybrid of European and African honey bees, is thought to displace native pollinators. After experimental introduction of Africanized honey bee hives near flowers, stingless bees became less abundant or harvested-less resource as visitation by Africanized honey bees increased. Shifts in resource use caused by colonizing Africanized honey bees may lead to population decline of Neotropical pollinators. PMID- 17743638 TI - THE FEEDING OF HORSES. PMID- 17743637 TI - NATURAL SCIENCE IN THE HIGH SCHOOL COURSE. PMID- 17743639 TI - CURRENT NOTES ON ANTHROPOLOGY.--IX. PMID- 17743641 TI - THE VARIABILITY OF SPECIFIC CHARACTERS AS EXHIBITED BY THE EXTINCT GENUS CORYPHODON. PMID- 17743640 TI - THE DE LAINCEL FUND FOR THE STUDY OF THE MAYA LANGUAGE AND ITS GRAPHIC SYSTEM. PMID- 17743643 TI - A Plea for the Study of Psychology. PMID- 17743642 TI - INDIAN NUMERALS. PMID- 17743644 TI - BLACK KNOT. PMID- 17743645 TI - Ball-Lightning. PMID- 17743646 TI - THE EVOLUTION OF ALGEBRA. PMID- 17743647 TI - THE EVOLUTION OF THE CEREBELLUM. PMID- 17743648 TI - ANTHROPOLOGY PAST AND PRESENT. PMID- 17743649 TI - Communication with Other Planets. PMID- 17743650 TI - The Man of the Future. PMID- 17743651 TI - Public Scrutiny of Research Grants. PMID- 17743652 TI - Women and Science. PMID- 17743654 TI - The Social Sciences and Society. PMID- 17743655 TI - Space: Highlights of Recent Research. PMID- 17743653 TI - Fellowships from Federal Funds. PMID- 17743656 TI - Foreign Grants: U.S. Reducing, but Not Ending, Support Program for Research Activities Abroad. PMID- 17743657 TI - Democratic Platform: "Science" Section Stresses Work in Space, Oceanography, and Atomic Energy. PMID- 17743658 TI - Science Advice: New Division for Science Policy Research Set Up in LRS to Aid Congress. PMID- 17743659 TI - Electron Microscopes: Duty on Foreign Models Restored by House; Action in Senate Is Uncertain. PMID- 17743660 TI - Congress Plays Geography: PHS Health Center Delayed Again as Maryland Site Is Firmly Excluded. PMID- 17743661 TI - Planetary Systems Associated with Main-Sequence Stars. AB - The luminosity function is used to estimate the number of invisible planet-like objects in the neighborhood of the sun, taking into account the likely chemical composition of planets in relation to the composition of main-sequence stars. There may be about 60 objects more massive than Mars for every visible star. An attempt is made to estimate the distribution of these planet-like cold bodies in relation to stars. It is suggested that stars, together with cold objects, were formed in clusters of bodies of random size distribution. Clusters averaging about 50 bodies each account for the observed distribution of frequencies of double and triple star systems relative to single stars. On this basis, virtually every star should have a planetary system associated with it. As a corollary, systems of cold bodies in which there are no luminous stars should be abundant. The possible distribution of planets around such stars has been studied, making use of the observed orbital characteristics of double star systems. It is concluded that favorable conditions for life processes may be far more abundant than has generally been thought possible. PMID- 17743662 TI - Isotopic Composition of Lead and Strontium from Ascension and Gough Islands. AB - Isotopic composition of lead and strontium has been determined in a series of rock samples from two islands on the Mid-Atlantic Ridge. Both interand intra island variations exist in the abundance of radiogenic isotopes of both elements. Lead from basalt of Ascension Island has a Pb(206)-Pb(204) ratio of 19.5, while the corresponding ratio at Gough Island is only 18.4. The Pb(208)-Pb(204) ratios from the two islands do not differ. Conversely, strontium from basalt of Ascension Island is less radiogenic than that from Gough Island basalts. The trachytes of both islands have lead and strontium that is more radiogenic than that found in the basalts. The inter-island differences indicate the existence of regional variations in the uranium-lead and rubidium-strontium ratios of the upper mantle source of these rocks and show that isotope compositions are a means for investigating chemical heterogeneities in the mantle. PMID- 17743663 TI - Infrared Absorption of Hydroxyl Groups in Kaolinite. AB - Effects of sample orientation on the hydroxyl absorption of kaolinite can be interpreted in terms of the structure indicated by x-ray investigations, in which the surface hydroxyl groups of each layer are directed toward the oxygen atoms on the surface of the next layer. PMID- 17743665 TI - Atmospheric Data May Be Misleading. PMID- 17743666 TI - Earth Movements: Alaskan Earthquake, 1964. PMID- 17743664 TI - Photoflashes: A Potential New Tool for Control of Insect Populations. AB - Imported cabbageworms, Pieris rapae (L.), were reared in cans exposed to light from fluorescent lamps for 10 hours daily. When larvae were exposed to daily electronic photoflashes scheduled 3 to 4 hours after the fluorescent lamp was turned off, pupae failed to diapause. Effective wavelengths are lower than those controlling photoperiodism in plants. The effective energies are about 1 joule per square centimeter. PMID- 17743667 TI - Forthcoming Events. PMID- 17743668 TI - Botanical Field Meeting. PMID- 17743669 TI - PERSONAL EXPERIENCE FROM A HALF CENTURY IN ENGINEERING EDUCATION. PMID- 17743670 TI - SCIENCE NEWS. PMID- 17743671 TI - MAXIMUM CONVENIENCE IN CITATIONS. PMID- 17743673 TI - UNIOVULAR TWINS IN MICE. PMID- 17743672 TI - FRESH-WATER. MEDUSAE IN ARKANSAS. PMID- 17743674 TI - THE UTAH ACADEMY OF SCIENCES, ARTS AND LETTERS. PMID- 17743676 TI - PHOSPHORYLATION OF GLYCOGEN IN VITRO. PMID- 17743675 TI - THE KENTUCKY ACADEMY OF SCIENCE. PMID- 17743677 TI - ON THE PROPERTIES OF RECTILINEAR FIGURES OF n DIMENSIONS. PMID- 17743678 TI - A PRELIMINARY REPORT ON THE SPECIFICITY OF KERATINS. PMID- 17743679 TI - A MECHANISM FOR THE AUTOMATIC IRRIGATION OF SAND CULTURES. PMID- 17743680 TI - A SIMPLIFIED TECHNIQUE FOR FORENSIC PRECIPITATION TESTS. PMID- 17743681 TI - Policy and the First Bombs. PMID- 17743682 TI - Headlines and Highlights. PMID- 17743683 TI - AAAS Chicago Meeting. PMID- 17743684 TI - Science in the News. PMID- 17743685 TI - Oxygen Isotope Paleotemperature Determinations of Australian Cainozoic Fossils. AB - Fossil marine shells collected in southern Victoria within half a degree of latitude of 38(1/2) degrees S have been analyzed for O(18)/O(16) by mass spectroscopy, and their paleotemperatures have been determined. For the genera Chlamys, Ostrea, and Glycymeris the temperature rises from early to mid-Tertiary, then falls again to the present. PMID- 17743687 TI - Policy and the First Bombs. PMID- 17743688 TI - Policy and the First Bombs. PMID- 17743690 TI - Radionuclides and Bone Cancer. PMID- 17743689 TI - Meteorology for Non-Science Majors. PMID- 17743691 TI - Arctic Waters. PMID- 17743692 TI - Arctic Waters. PMID- 17743693 TI - Science and the Election. PMID- 17743694 TI - Essay Tests Can Be Standardized. PMID- 17743695 TI - The Lunar Surface. PMID- 17743696 TI - Able Students Still Choose Science. PMID- 17743697 TI - Challenge to Tax Exemption. PMID- 17743698 TI - Lasers for Length Measurement: Lasers are useful in metrology because of the high coherence and intensity of the light they produce. PMID- 17743699 TI - An Absolute Spectrofluorometer: A new instrument has been developed for simple determinations of absolute fluorescence spectra. PMID- 17743700 TI - Precision Digital Tide Gauge: Vibrating wire pressure transducers provide sea level measurements to the nearest one-tenth millimeter. PMID- 17743701 TI - Seismic Measurements on the Ocean Bottom: New instruments are used to study earth's crustal structure and seismic background. PMID- 17743702 TI - Nuclear Magnetic Resonance Spectroscopy in Superconducting Magnetic Fields. AB - The first high-resolution nuclear magnetic resonance spectrometer operated at 30 Mcy/sec (7.05 kilogauss). The magnets constituted the only major obstacle to raising the frequency, but by continuous development over 10 years this frequency for proton resonance was increased to 100 Mcy/sec (23.4 kilogauss). Now, in one step, a system has been made to operate at twice this frequency and field intensity. It is not expected that superconducting magnets will generally replace iron magnets, but it is interesting to note that very few laboratories use the 30 and 40-Mcy/sec proton systems today. Notwithstanding the cost and operating problems of the superconducting magnet system for the nuclear magnetic resonance spectrometer, the fact that this is the only practical means of developing both a stable and a high-intensity field puts it in a class by itself. For this reason, even though the maintenance of spectrometers with superconducting magnets requires rather specialized skills, this type of instrumentation will clearly have an important role in advancing scientific knowledge, by making possible analyses which have not been possible with presently available instruments. PMID- 17743703 TI - The Election: Partisan Activity of Scientists Unlikely to Sow Discord in Scientific Community. PMID- 17743704 TI - C. P. Snow: Corridors of Power Is Novel about Nuclear Policy and Politics, Closed and Open. PMID- 17743705 TI - Elliott Committee: Latest Study Calls for Improvement in Data on Scientific Manpower Problems. PMID- 17743706 TI - Medical Research: Congress Adds $10 Million to President's Budget for Special Studies on Leukemia. PMID- 17743707 TI - Silicon Oxynitride: A Meteoritic Mineral. AB - Silicon oxynitride, a new mineral, has been discovered in the Jajh deh Kot Lalu enstatite chondrite. Nitrogen and oxygen have been measured quantitatively with an electron microprobe by means of prototypes of newly developed curved crystal detection systems. X-ray diffraction patterns were obtained from silicon oxynitride separated from the meteorite and from synthetic Si(2)N(2)O. PMID- 17743709 TI - Oscillations of Quasars. AB - Rotation in addition to free gravitational motion can produce oscillations in a large spherical mass of gas. The theory may provide an explanation of the variations of brightness in such objects as 3C273. PMID- 17743708 TI - Chemical Variations in a Granitic Pluton and Its Surrounding Rocks. AB - New techniques of x-ray fluorescence spectrography have provided, for the first time, abundant data regarding chemical variability of granitic rocks on different scales. The results suggest that current designs of sampling plans for trend surface analysis should be modified; in particular several specimens, preferably drillcores, may be required at each locality. PMID- 17743710 TI - High-Voltage Laue X-ray Photography of Large Single Crystals. AB - The perfection of relatively large single crystals can be tested by Laue transmission x-ray diffraction photographs by using much higher voltages for the x-ray generation than are used in conventional diffraction experiments. The technique can be used for determining the orientation spread of subcrystal units and for studying the loss of primary extinction due to occluded chemical impurities. An advantage of this method is its possible application to crystals inside polycrystalline or glass containers. PMID- 17743711 TI - Crystal and Molecular Structure of Ferrichrome A. AB - The crystal structure of ferrichrome A (C(41)H(58)N(9)O(20)Fe.4H(2)O) has been determined by x-ray diffraction. The amino acid sequence in the hexapeptide ring is confirmed to be -Orn-Orn-Orn-Ser-Ser-Gly-, and the conformation of this ring is trans at each peptide linkage. The absolute configuration of the three hydroxamate rings at the iron atom is that of a left-handed propeller. Disorder is found concerning the positions of some of the side chains and one of the four water molecules. PMID- 17743712 TI - Sodium Perxenate and Xenon (II) Difluoride Reduction at the Dropping-Mercury Electrode. AB - Sodium perxenate in alkaline solutions is reduced in a single step to xenon at the dropping-mercury electrode. The half-wave potential for perxenate changes from -0.21 to -0.31 volts against a Hg(2)SO(4)-Hg reference electrode in the pH range 10.1 to 11.3. Xenon (II) difluoride in acidic solution is reduced in a single step to xenon, at the potential of approximately zero against the Hg2SO4 Hg reference electrode. The reduction wave is followed by a broad maximum which can be effectively suppressed by fluoride ion. The diffusion current varies in linear fashion with concentration. PMID- 17743713 TI - Biophysics. PMID- 17743715 TI - Forthcoming Events. PMID- 17743714 TI - American Association of Physical Anthropologists. PMID- 17743716 TI - THE WASHINGTON ACADEMY OF SCIENCES. PMID- 17743717 TI - THE SMITHSONIAN INSTITUTION. PMID- 17743718 TI - HARRISON ALLEN. PMID- 17743719 TI - HIGH SCHOOL BOTANY. PMID- 17743720 TI - EXTRA-ORGANIC EVOLUTION. PMID- 17743721 TI - BINOCULAR FACTORS IN MONOCULAR VISION. PMID- 17743722 TI - A NEW NAME FOR THE NOVA SCOTIA FOX. PMID- 17743723 TI - THE AMERICAN CHEMICAL SOCIETY. PMID- 17743724 TI - CURRENT NOTES ON PHYSIOGRAPHY. PMID- 17743725 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17743726 TI - NOTES ON INORGANIC CHEMISTRY. PMID- 17743727 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17743728 TI - DISCUSSION AND CORRESPONDENCE. PMID- 17743729 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17743730 TI - THE THIRD INTERNATIONAL CONGRESS OF APPLIED CHEMISTRY. PMID- 17743731 TI - A CHARACTER REGULARLY ACQUIRED BUT NEVER INHERITED. PMID- 17743732 TI - ELIZABETH THOMPSON SCIENCE FUND. PMID- 17743733 TI - THE GREAT SALT DESERT OF PERSIA. PMID- 17743734 TI - HYGIENE AT ANN ARBOR. PMID- 17743735 TI - THE APPLICATIONS OF HYPNOTISM. PMID- 17743736 TI - A Suggestion on Telepathy. PMID- 17743737 TI - PROGRESS IN HORTICULTURAL SCIENCE. PMID- 17743739 TI - THE LEVEL OF THE OCEAN DURING PART OF THE CENOZOIC ERA. PMID- 17743738 TI - PREHISTORIC QUARRIES AND IMPLEMENTS OF PRE-AMERINDIAN ASPECT IN NEW MEXICO. PMID- 17743740 TI - VEGETATION ON SHELL MOUNDS, LOWER CALIFORNIA. PMID- 17743741 TI - SOIL CORROSION. PMID- 17743744 TI - THE EXISTENCE OF MERCERIZED CELLULOSE AND ITS ORIENTATION IN HALICYSTIS AS INDICATED BY X-RAY DIFFRACTION ANALYSIS. PMID- 17743743 TI - WATER-SOLUBLE DERIVATIVES OF P-AMINOBENZENE-SULFONAMIDE (SULFANILAMIDE). PMID- 17743742 TI - THE RESPONSE OF THE MYASTHENIC STATE TO GUANIDINE HYDROCHLORIDE. PMID- 17743745 TI - DISCOLORED PLATES. PMID- 17743746 TI - SUSTAINING LONGITUDINAL VIBRATIONS IN RODS. PMID- 17743747 TI - PRESENCE OF HOST KEEPS PARASITES ALIVE IN CAPTIVITY. PMID- 17743748 TI - ORGANIZATION OF AMERICAN SCIENTISTS FOR THE WAR. II. PMID- 17743749 TI - THE BIOCHEMISTRY OF ANTHOCYANINS. AB - 1. An explanation has been given for the effect of subdued light on the development of anthocyanins. This effect was observed by von Sachs and by Sorby seventy years ago. Nobody has made an exhaustive study of the subject, although Askenasy, Hugo Fischer and others have done work along these lines. 2. When a flavone is reduced to an anthocyanin, as with the Japanese quince, cutting off ultra-violet light prevents the formation of the anthocyanin. 3. When the anthocyanin is formed by the hydrolysis of a leuco-anthocyanin, cutting off of ultraviolet light will not necessarily prevent the formation of the anthocyanin. This occurs with the geranium. 4. We do not know at all approximately how many or which flowers belong to what I call the flavone type and how many or which to the leuco-anthocyanin type. 5. After the biochemistry of the anthocyanins shall have been worked out the botanists and chemists should concentrate on the biochemistry of the carotenes, the lycopenes and chlorophyll. PMID- 17743750 TI - JOSEPH SWEETMAN AMES. PMID- 17743751 TI - THE RESOURCES OF VIRGINIA. PMID- 17743752 TI - THE AQUARIUM OF THE ZOOLOGICAL PARK, LONDON. PMID- 17743753 TI - MESSAGE FROM CHINESE MEN OF SCIENCE. PMID- 17743755 TI - RARE CHEMICALS. PMID- 17743754 TI - GIFTS AND GRANTS TO THE UNIVERSITY OF WISCONSIN. PMID- 17743756 TI - THE PRESIDENT OF THE SOCIETY OF CHEMICAL INDUSTRY. PMID- 17743757 TI - THE MATHEMATICAL ASSOCIATION OF AMERICA. PMID- 17743758 TI - THE NEW PREFERENCE AND LIMITATION ORDER ON LABORATORIES AND LABORATORY EQUIPMENT. PMID- 17743760 TI - RIBOFLAVIN-VITAMIN B2 IN SOIL. PMID- 17743759 TI - CENSUS AREAS FOR THE UNITED STATES, 1940. PMID- 17743761 TI - APPARENT TIME ACCELERATION WITH AGE OF THE INDIVIDUAL. PMID- 17743762 TI - OBSERVATIONS CONCERNING THE ETIOLOGY OF PRIMARY ATYPICAL PNEUMONIA. PMID- 17743763 TI - LOSS OF PROPRIOCEPTIVE REFLEXES FOLLOWING RETROGRADE DEGENERATION. PMID- 17743764 TI - AN IMPROVED INSTRUMENT FOR MEASURING CAPILLARY FRAGILITY. PMID- 17743765 TI - A SIMPLE TIMING DEVICE FOR SPEAKERS. PMID- 17743767 TI - SHERBURNE WESLEY BURNHAM, 1838-1921. PMID- 17743766 TI - A SIMPLIFIED ALL-PURPOSE GRAVITY WRITING LEVER. PMID- 17743768 TI - THE CENTENNIAL EXPEDITION OF INDIANA UNIVERSITY TO PERU. PMID- 17743770 TI - THE EARLY HISTORY OF LITMUS IN BACTERIOLOGY. PMID- 17743769 TI - GENETICS OF THE "CHINCHILLA" RABBIT. PMID- 17743771 TI - NEWSPAPER SCIENCE. PMID- 17743772 TI - ANOTHER DRIFT BOTTLE WHICH CROSSED THE ATLANTIC. PMID- 17743773 TI - THE MECHANISM OF AN ENZYME REACTION AS EXEMPLIFIED BY PEPSIN DIGESTION. PMID- 17743774 TI - KNIPP'S SINGING TUBE. PMID- 17743775 TI - THE AMERICAN PHYSIOLOGICAL SOCIETY. PMID- 17743776 TI - ENGINEERING SCIENCE BEFORE, DURING AND AFTER THE WAR. PMID- 17743777 TI - A QUESTION CONCERNING THE NATURE OF VELOCITY. PMID- 17743778 TI - JACQUES DANNE. PMID- 17743779 TI - EMIL FISCHER AFTER THE WAR. PMID- 17743780 TI - SCIENCE AND THE PRESS. PMID- 17743781 TI - AURORAL DISPLAYS AND THE MAGNETIC NEEDLE. PMID- 17743782 TI - THE AURORAL DISPLAY OF SEPTEMBER 18. PMID- 17743783 TI - AGRICULTURAL METEOROLOGY. PMID- 17743784 TI - WHITE CORN VS. YELLOW CORN AND A PROBABLE RELATION BETWEEN THE FAT-SOLUBLE VITAMINE AND YELLOW PLANT PIGMENTS. PMID- 17743785 TI - THE AMERICAN MATHEMATICAL SOCIETY. PMID- 17743787 TI - Retinal Flicker and Imprinting. PMID- 17743786 TI - Stratospheric Fallout. PMID- 17743788 TI - Idealism for Export. PMID- 17743789 TI - Ancient Agriculture in the Negev: Archeological studies and experimental farms show how agriculture was possible in Israel's famous desert. PMID- 17743791 TI - The Budget: Kennedy Asks for Science Increases beyond the Increases Ike Recommended. PMID- 17743790 TI - The College-Student Image of the Scientist: Scientists are seen as intelligent and hard-working but also as uncultured and not interested in people. PMID- 17743792 TI - Growth of Sporangiophores of Phycomyces Immersed in Water. AB - Sporangiophores of Phycomyces are capable of sustained growth when immersed in aerated water, and under these conditions they are negatively phototropic. PMID- 17743793 TI - Forthcoming Events. PMID- 17743794 TI - Entomology and Human Welfare. PMID- 17743795 TI - CHEMICAL PRINCIPLES OF SOIL CLASSIFICATION. PMID- 17743797 TI - WOLCOTT GIBBS. PMID- 17743796 TI - EXTRACTS FROM PRESIDENT ROOSEVELT'S MESSAGE TO THE CONGRESS. PMID- 17743799 TI - FRENCH VITAL STATISTICS. PMID- 17743798 TI - PRESIDENT ROOSEVELT'S AFRICAN TRIP. PMID- 17743801 TI - THE AMERICAN SOCIETY OF ANIMAL NUTRITION. PMID- 17743800 TI - SYMPOSIUM ON CORRELATION. PMID- 17743803 TI - THE FIVE HUNDREDTH ANNIVERSARY OF THE UNIVERSITY OF LEIPZIG. PMID- 17743802 TI - THE AMERICAN SOCIETY OF NATURALISTS. PMID- 17743804 TI - THE ODONATA OF MEXICO. PMID- 17743806 TI - THE ACCLIMATIZATION OF AN ALFALFA VARIETY IN MINNESOTA. PMID- 17743805 TI - MALARIA IN THE WEST INDIES. PMID- 17743807 TI - THE CONVOCATION WEEK MEETINGS OF SCIENTIFIC SOCIETIES. PMID- 17743808 TI - SCIENCE NEWS. PMID- 17743809 TI - SCIENCE IN THE PUBLIC PRESS. PMID- 17743810 TI - THE LANDING PLACE OF DE SOTO. PMID- 17743811 TI - PROGRESSIVE DEAFNESS. PMID- 17743812 TI - AGAIN "WHY DANDELIONS?". PMID- 17743813 TI - A DEVICE FOR MICROMANIPULATION. PMID- 17743814 TI - THE OXIDATION OF CARBON MONOXIDE CATALYZED BY NITROGEN DIOXIDE. PMID- 17743815 TI - THE ACTION OF HIGH FREQUENCY SOUND WAVES ON TOBACCO MOSAIC VIRUS. PMID- 17743817 TI - GROWTH OF YEAST BELOW ZERO. PMID- 17743816 TI - A CONSTANT-RATE DROPPING DEVICE FOR LIQUIDS. PMID- 17743818 TI - THE VITAMIN D ASSAY OF THE "REFERENCE COD-LIVER OIL". PMID- 17743819 TI - SCIENCE AND LIBERAL EDUCATION. PMID- 17743820 TI - PLAIN WRITING. PMID- 17743821 TI - SOIL FERTILITY. PMID- 17743822 TI - THE THIRTEENTH NEW ENGLAND INTERCOLLEGIATE GEOLOGICAL EXCURSION. PMID- 17743823 TI - THE WILLARD GIBBS PROFESSORSHIP OF RESEARCH IN PURE CHEMISTRY. PMID- 17743824 TI - FREDERIC WARD PUTNAM. PMID- 17743825 TI - ELECTROMOTIVE PHENOMENA AND MEMBRANE PERMEABILITY. PMID- 17743826 TI - WHAT IS HELLENISM? PMID- 17743827 TI - UNIVERSITIES AND UNPREPAREDNESS. PMID- 17743828 TI - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES. PMID- 17743829 TI - ON THE OCCURRENCE IN THE SOUTHERN HEMISPHERE OF THE BASKING OR BONE SHARK,CETORHINUS MAXIMUS. PMID- 17743830 TI - LABELING CHEMICAL SPECIMENS. PMID- 17743832 TI - THE DEDICATION OF THE NEW SITE OF COLUMBIA UNIVERSITY. PMID- 17743831 TI - REPORT OF THE SAN FRANCISCO MEETING OF SECTION F OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. II. PMID- 17743834 TI - THE INFLUENCE OF CARBON DIOXIDE ON THE PROTOPLASM OF LIVING PLANT CELLS. PMID- 17743833 TI - PSYCHOLOGICAL NOTES UPON SLEIGHT-OF-HAND EXPERTS. PMID- 17743835 TI - NOTES ON CERTAIN UNDESCRIBED CLAY OCCURRENCES IN MISSOURI. PMID- 17743837 TI - SOURCE OF X-RAYS. PMID- 17743836 TI - NOTE ON A BREATHING GAS WELL. PMID- 17743838 TI - CURRENT STUDIES IN EXPERIMENTAL GEOLOGY. PMID- 17743840 TI - RADIATION FROM URANIUM SALTS. PMID- 17743839 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17743841 TI - VIVISECTION IN THE DISTRICT OF COLUMBIA. PMID- 17743842 TI - ON ROOD'S DEMONSTRATION OF THE REGULAR OR SPECULAR REFLECTION OF THE RONTGEN RAYS BY A PLATINUM MIRROR. PMID- 17743843 TI - PSEUDO-SCIENCE IN METEOROLOGY. PMID- 17743844 TI - THE USE OF THE TOW-NET FOR COLLECTING PELAGIC ORGANISMS. PMID- 17743846 TI - RADIOACTIVITY. PMID- 17743845 TI - ZOOLOGY AND BIOLOGY. PMID- 17743847 TI - THE ORIGIN OF THE EARTH'S LAND FORMATIONS. PMID- 17743848 TI - THE GREAT SMOKY MOUNTAINS NATIONAL PARK. PMID- 17743849 TI - THE BIOLOGICAL RESEARCH INSTITUTE OF THE ZOOLOGICAL SOCIETY OF SAN DIEGO. PMID- 17743850 TI - THE DETROIT MEETING OF THE AMERAT WOODS HOLE. PMID- 17743851 TI - THE MARINE BIOLOGICAL LABORATORY AT WOODS HOLE. PMID- 17743852 TI - THE FIRST THOUSAND MATHEMATICAL WORKS PRINTED IN AMERICA. PMID- 17743853 TI - THE INCIDENCE OF HYDROGEN SULFIDE AT KILAUEA SOLFATARA PRECEDING THE 1940 MAUNA LOA VOLCANIC ACTIVITY. PMID- 17743854 TI - SUMMARIZED PROCEEDINGS OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE FROM 1934 TO 1940. PMID- 17743855 TI - MORPHOLOGICAL AND FUNCTIONAL RECOVERY OF THE PANCREATIC ISLANDS IN DIABETIC CATS TREATED WITH INSULIN. PMID- 17743856 TI - THE NEURO-MOTOR MECHANISM OF THE SMALL BLOOD VESSELS OF THE FROG. PMID- 17743858 TI - MOLECULAR WEIGHT BY ISOTHERMIC DISTILLATION. PMID- 17743857 TI - EGG-WHITE INJURY IN CHICKS AND ITS RELATIONSHIP TO A DEFICIENCY OF VITAMIN H (BIOTIN). PMID- 17743859 TI - A SIMPLE STAIN FOR TISSUE CULTURES. PMID- 17743860 TI - THE APRIL MEETING OF THE NATIONAL ACADEMY OF SCIENCES. PMID- 17743861 TI - A second phalanx in the third digit of a carinate-bird's wing. PMID- 17743862 TI - Mr. Hampden's designation of Sir Isaac Newton. PMID- 17743863 TI - THE RUSSIAN BASE OF OPERATIONS AGAINST INDIA. PMID- 17743864 TI - ROADS FROM INDIA TO CENTRAL ASIA. PMID- 17743866 TI - THE LEGAL LANGUAGE OF INDIA. PMID- 17743865 TI - THE RACES OF CENTRAL ASIA. PMID- 17743867 TI - THE EFFICIENCY OF THE STEAM-ENGINE. PMID- 17743868 TI - HAULING A STEAMER THROUGH AFRICA. PMID- 17743869 TI - METEOROLOGICAL NOTES. PMID- 17743870 TI - THE RUSSIAN EMBASSY TO AFGHANISTAN. PMID- 17743872 TI - TIFLIS AND BAKU. PMID- 17743871 TI - THE RUSSIANS AT THE GATES OF HERAT. PMID- 17743873 TI - RECENT PROGRESS IN AERONAUTICS. PMID- 17743874 TI - THE AMERICAN MUSEUM OF NATURAL HISTORY. PMID- 17743875 TI - MOSQUITO EXTERMINATION WORK IN NEW JERSEY. PMID- 17743876 TI - PROPOSED LINCOLN SCHOOLS OF SCIENCE. PMID- 17743877 TI - THE EIGHTH INTERNATIONAL ZOOLOGICAL CONGRESS. PMID- 17743878 TI - FIRST AWARD OF THE LANGLEY MEDAL. PMID- 17743879 TI - HARVARD UNIVERSITY AND THE MASSACHUSETTS INSTITUTE OF TECHNOLOGY. PMID- 17743880 TI - THE RIGHT AND THE WRONG IN POPULAR SCIENCE BOOKS. PMID- 17743881 TI - THE RIABOUSCHINSKY EXPEDITION UNDER THE AUSPICES OF THE IMPERIAL RUSSIAN GEOGRAPHICAL SOCIETY. PMID- 17743882 TI - THE AMERICAN CHEMICAL SOCIETY. PMID- 17743883 TI - THE THIRTY-NINTH GENERAL MEETING OF THE AMERICAN CHEMICAL SOCIETY AND THE MEETING OF SECTION C OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17743884 TI - RESEARCH IN SOME ASPECTS OF DISEASE ASSOCIATED WITH THE FIELDS OF ZOOLOGY, ENTOMOLOGY AND PARASITOLOGY. PMID- 17743885 TI - EXTRACTS FROM ESSAYS OF LEONARDO DA VINCI. PMID- 17743887 TI - AN EGYPTIAN MATHEMATICAL PAPYRUS IN MOSCOW. PMID- 17743886 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17743888 TI - CONCENTRATIONS OF IONS OF INSOLUBLE OR UNDISSOCIATED SALTS IN SOLUTION. PMID- 17743890 TI - FEDERATIONS OF SCIENTIFIC MEN. PMID- 17743889 TI - THE INTERNATIONAL WORK OF SCIENTIFIC SYNTHESIS. PMID- 17743891 TI - ZIRCONIUM FRACTIONS. PMID- 17743892 TI - PARAMAGNETISM AND THE THEORY OF QUANTA. PMID- 17743893 TI - THE AMERICAL CHEMICAL SOCIETY. PMID- 17743894 TI - SCIENCE NEWS. PMID- 17743895 TI - HOW STATE ACADEMIES OF SCIENCE MAY ENCOURAGE SCIENTIFIC ENDEAVOR AMONG HIGHSCHOOL STUDENTS. PMID- 17743896 TI - THE PRODUCTION OF FEVER IN MAN BY SHORT RADIO WAVES. PMID- 17743897 TI - A PLEA FOR SANITY IN NOMENCLATURE. PMID- 17743898 TI - TEST OF THE WEGENER HYPOTHESIS BY MEANS OF GEODETIC DATA IN INDIA. PMID- 17743899 TI - TEREDOLITHUS, A NEW COLLECTIVE GROUP NAME. PMID- 17743900 TI - ANTAGONISM BETWEEN ZOOPHARMACOLOGY AND PHYTOPHARMACOLOGY. PMID- 17743901 TI - THE BANANA IN EARLY BOOKS: FRUIT OR STEM? PMID- 17743902 TI - DISCOVERY OF PHOSPHORUS FIXING COMPOUND IN THE SOIL. PMID- 17743903 TI - THE PRESIDENCY OF THE BRITISH ASSOCIATION. PMID- 17743904 TI - THE COLOR-BLINDNESS OF INDIANS. PMID- 17743906 TI - A METHOD OF SECURING MARINE INVERTEBRATES. PMID- 17743905 TI - AN ELECTROMAGNETIC PUMP. PMID- 17743907 TI - DETERMINATION OF POLYMERIZATION OF SOME POLYMER FORMALDEHYDES BY X-RAY METHODS. PMID- 17743908 TI - TURNING OF THE SPERM IN THE ACRIDIAN FOLLICLE. PMID- 17743909 TI - Security. PMID- 17743910 TI - Surface Properties of Semiconductors. PMID- 17743911 TI - A. C. Schaeffer, Mathematician. PMID- 17743912 TI - News of Science. PMID- 17743913 TI - Nonphotosynthetic Light Requirement in Lemna minor and Its Partial Satisfaction by Kinetin. PMID- 17743914 TI - Stratigraphy of the Wisconsin Glacial Stage along the Northwestern Shore of Lake Erie. PMID- 17743916 TI - EQUIPMENT NEWS. PMID- 17743915 TI - Meetings and Societies. PMID- 17743917 TI - Science and the Race Problem. PMID- 17743918 TI - Letters to the Editor. PMID- 17743919 TI - Population Problems and Infectious Diseases. PMID- 17743920 TI - Who Should Teach Engineering? PMID- 17743921 TI - Freedom in Large Laboratories. PMID- 17743922 TI - Cigareftes: Polonium-210. PMID- 17743924 TI - The Deep Structure of Continents. PMID- 17743923 TI - New Goals for Science in Britain. PMID- 17743925 TI - Mathematicians in Industry -- The First 75 Years. PMID- 17743926 TI - LBJ and Science: Policies Marked by Continuity, but a Few Events Suggest Developments for Future. PMID- 17743927 TI - Conservation: Local and National Interests Conflict on Proposals Awaiting Action in Congress. PMID- 17743928 TI - Radio Observation of the Electromagnetic Emission from Warm Clouds. AB - Microdischarges observable at 30 and 50 Mcy/sec appear from within cumulus clouds in an early stage of their development whether the temperatures within the clouds are above or below 0 degrees C. Laboratory observations of radio emission from colliding drops may provide information on the physics of clouds in the atmospheres of this and other planets. PMID- 17743929 TI - Harappa Culture: New Evidence for a Shorter Chronology. AB - Radiocarbon dates suggest a total time spread of 550 years, from about 2300 to 1750 B. C., for the Harappa culture. PMID- 17743930 TI - High-Pressure Phase Transition in Tin Telluride. AB - At 18 kilobars, tin telluride transforms from a sodium chloride-type structure to an orthorhombic crystal structure (space group Pnma). This structural change is accompanied by a 360-percent increase in electrical resistivity. PMID- 17743931 TI - Radioactive Myoinositol: Incorporation into Streptomycin. AB - Radioactive myoinositol was rapidly incorporated into streptomycin by Streptomyces griseus. All the incorporated radioactivity was found in the streptidine moiety of the antibiotic, as shown by chemical degradation of the streptomycin. To a certain extent inositol reversed the depressing effect of phosphate on the production of the antibiotic. PMID- 17743932 TI - Regenerating Tissues from the Cockroach Leg: A System for Studying in vitro. AB - Regenerating leg tissue of Leucophaea maderae shows considerable activity in vitro. Migrations of ameboid and fiber-like cells from the explant take place, vesicles are produced, and interaction occurs between tissues. The system described facilitates the study of these activities in vitro. PMID- 17743933 TI - Pure Maple Syrup: Nutritive Value. AB - Variations in concentrations of sugar, nitrogen, phosphorus, potassium, calcium, and magnesium of sap from sugar maple (Acer saccharum, Marsh.) trees are related to the time of sap collection and result in variation of the same components in pure maple syrup. Thirty milliliters (one fluid ounce) of pure maple syrup may contain 3 to 6 mg of phosphorus, 10 to 30 mg of potassium, 40 to 80 mg of calcium, and 4 to 25 mg of magnesium. PMID- 17743934 TI - Weights and Measures. PMID- 17743935 TI - Forfhcoming Events. PMID- 17743936 TI - Human Diploid Cell Strains. PMID- 17743937 TI - Research in the Social Sciences. PMID- 17743938 TI - Judges Named for AAAS-George Westinghouse Science Writing Award. PMID- 17743939 TI - Species Density Analysis of Silicate Glass Structure. PMID- 17743940 TI - Mechanism of Spontaneous Cure in Puberty of Ringworm of the Scalp. AB - With onset of puberty, the sebaceous glands of the scalp start to secrete a sebum which contains, in higher concentration than before, lowboiling saturated fatty acids with selective fungistatic and fungicidal action on M. audouini. Highly active normal aliphatic monobasic acids having odd numbers of carbon atoms, including pelargonic acid, have been isolated from hair fat of adults. The "adult type" of hair fat does not kill the fungus spores within the hair but prevents infection of the new hair following the old infected hair in the process of shedding. Detailed reports are to be published elsewhere. PMID- 17743941 TI - Inhibition of the Catalyzed Thermal Decomposition of DDT. PMID- 17743942 TI - Isolation of Type A Influenza Virus in Recent Epidemic in Chicago Area. PMID- 17743943 TI - Effect of Streptomycin on Budwood Infected With Phytomonas pruni. PMID- 17743944 TI - Terrestrial Thermodynamics of an Ice Age. PMID- 17743946 TI - Initiation of Geological Investigations in the Panama Canal Zone. PMID- 17743945 TI - On the Term "Normality Factor". PMID- 17743947 TI - Rediscovery in the Vitamin C Field. PMID- 17743950 TI - Photocopying: How Much? PMID- 17743949 TI - The Occurrence of Crystalline Naringin on Grapefruit Rind. PMID- 17743948 TI - Rockets vs. Meteoroids. PMID- 17743951 TI - FDA Committee Decision Explained. PMID- 17743952 TI - Biology Worldwide. PMID- 17743953 TI - Half-Truth and Consequences. PMID- 17743955 TI - Letters to the Editor. PMID- 17743954 TI - Letters to the Editor. PMID- 17743956 TI - Owner of Notebooks Sought. PMID- 17743958 TI - Animal-Care Legislation: Why Should Scientists Object? PMID- 17743957 TI - Social Science in Population Control. PMID- 17743959 TI - Conservation and Natural Beauty. PMID- 17743960 TI - Academic Freedom and Political Liberty. PMID- 17743961 TI - Pure Research, Cultism, and the Undergraduate. PMID- 17743962 TI - Reuss Committee: New Probe Planned into Priorities for R&D. PMID- 17743964 TI - Vietnam: Growing War and Campus Protests Threaten Student Deferments. PMID- 17743963 TI - The 200-Bev Machine: University Compact Offers Its Services. PMID- 17743965 TI - E. B. Chain Accused of Contempt of Italian Judiciary. PMID- 17743966 TI - Chromium-51 as a Radioactive Tracer of Columbia River Water at Sea. AB - The plume of the Columbia River was followed 350 kilometers to sea by measurement of its chromium-51 content. This radioactive tag, introduced into the river by nuclear reactors at Hanford, Washington, promises to provide a useful oceanographic tool for determining rates of transport and mixing, and for identifying plume waters in the presence of other sources of fresh water. PMID- 17743967 TI - Avifauna: Turnover on Islands. AB - The percentage of endemic species of birds on islands increases with island area at a double logarithmic rate. This relation is apparently due to extinction, which is more rapid the smaller the island. The turnover resulting from extinction and replacement appears to be far more rapid than hitherto suspected. PMID- 17743968 TI - Isoprenoid Hydrocarbons in Recent Sediments: Presence of Pristane and Probable Absence of Phytane. AB - Pristane (2,6,10,14-tetramethylpentadecane) has been isolated from two recent marine sediments. Unlike their ancient counterparts, these sediments contain no detectable phytane. These two facts suggest a biochemical origin for at least a fraction of the sedimentary pristane and a later, geochemical formation of phytane. Commercial reagent-grade solvents (pentane, isooctane, methanol) contain appreciable quantities of fossil pristane and probably phytane. PMID- 17743969 TI - Fast Reactions of Ascorbic Acid and Hydrogen Peroxide in Ice, a Presumptive Early Environment. AB - Nonenzymatic decomposition of hydrogen peroxide proceeded more rapidly in ice than in liquid water. At 5 x 10(-7)M ferric chloride or 10(-8)M cupric chloride, breakdown of hiydrogen peroxide was significant at -11 degrees and -18 degrees but negligible at +1 degrees C. Ascorbic acid oxidation was faster in ice both with or without added metalion. Nonparallel effects of metals and pH indicate, mechanism changes in ice. PMID- 17743970 TI - Nucleic Acid and Protein Changes in Wheat Leaf Nuclei during Rust Infection. AB - Microspectrophotometric measurements of DNA, RNA, histone, and total protein in the nuclei of mesophyll cells of Little Club wheat leaves were made at intervals after infection with the stem rust fungus. No change in host DNA was found within 6 days after inoculation, but there were decreases in histones and marked increases in RNA and acidic proteins as early as 2 days after inoculation. PMID- 17743971 TI - Caterpillar Feeding on a Sundew Plant. AB - The caterpillar of a plume moth (Trichoptilus parvulus) was found feeding on a sundew plant (Drosera capillaris) in Florida. The larva eats the stalked glands with their sticky secretion, the leaf blades, and even dead insects trapped by the plant. PMID- 17743973 TI - Sex Conversion Induced by Hydrostatic Pressure in the Marine Copepod Tigriopus californicus. AB - High hydrostatic pressure applied to the naupliar larval stages of the marine copepod Tigriopus californicus converts some individuals that would have become males into females. The copepodid stages are not sensitive to pressureinduced conversion. PMID- 17743972 TI - Callose: Lateral Movement of Assimilates from Phloem. AB - Brief heating of cotton petioles increased phloem callose and decreased lateral movement of assimilates containing carbon-14. The heat-induced phloem callose appears to have been responsible for part of this decrease; we conclude, therefore, that lateral movement from sieve tubes was along proto plasmic connections. PMID- 17743974 TI - Gegenschein: Photographs. PMID- 17743975 TI - Convection Plumes from Trees. PMID- 17743977 TI - Forthcoming Events. PMID- 17743976 TI - Surface Phenomena. PMID- 17743979 TI - BITNET Headed for New Frontiers. PMID- 17743978 TI - This week in science. PMID- 17743980 TI - Emissions Trading Goes Global: Spurred on by critics, the Administration is set to propose a world market in emissions of greenhouse gases. PMID- 17743982 TI - The Great Asteroid Roast: Wast It Rare or Well-Done?: Many astronomers now believe most of the asteroids were cooked early on rather than being largely unaltered primordial stuff. PMID- 17743981 TI - Global warming continues in 1989. PMID- 17743983 TI - S Asteroids at Controvery's Core. PMID- 17743984 TI - Japan reaches for the moon. PMID- 17743985 TI - Deutch bows out. PMID- 17743986 TI - Uptown goes down. PMID- 17743987 TI - Congress and animal rights. PMID- 17743988 TI - Anxiety in Academe Over DOD Cuts. PMID- 17743989 TI - Experiments on the structure of an individual elementary particle. AB - Research begun in the early 1970s on geonium is reviewed. Genoium is a man-made atom, created at liquid-helium temperature in ultrahigh vacuum from an individual electron in magnetic and electric trapping fields. For this atom the electron gyromagnetic ratio g = 2. 000 000 000 110(60) has been measured in microwave spectroscopy experiments after subtraction of quantum electrodynamics shifts. The g - g(Dirac) = 11 x 10(-11) excess over the value g(Dirac) = 2 for the theoretical Dirac point electron suggests for the electron of nature a corresponding excess radius R(e) - R(Dirac) over the Dirac radius R(Dirac) = 0 and a spatial structure. From a plot of measured g and R values for the near Dirac particles electron, proton, triton, and helium-3 an electron radius R(e) approximately 10(-20) centimeter is extrapolated. In a speculation, the triton proton-quark model has been extended to the electron, to a succession of subquarks, and finally to the "cosmon." Rapid decay of a cosmon-anticosmon pair created from the "nothing" state in a spontaneous quantum jump initiated the Big Bang. PMID- 17743990 TI - Direct Observation and Analysis of CuO2 Shear Defects in La2-xSrxCuO4. AB - Direct observations of CuO(2) sheet defect structures in superconducting La(2 x)Sr(x)CuO(4), with x in the range 0.05 crystallographic directions, by a pure shear mechanism along the edge of the octahedral copper-oxygen units. The line defects are partial screw dislocations, with characteristic displacement vectors of the type <(a/2), 0, (c/6)>, bounding the stacking faults. The existence of this type of defect demonstrates that there is an oxygen deficiency within the CuO(2) layers. However, unlike the open ReO(3) type-related structures, the packing density of the K(2)NiF(4) structure necessarily requires that anion defects be accompanied by the loss of cations of the A type (lanthanum, strontium). Under identical synthesis conditions, no defects are observed in the parent compound La(2)CuO(4). PMID- 17743992 TI - AAAS Fellow Nominations. PMID- 17743991 TI - An empirical model of total solar irradiance variation between 1874 and 1988. AB - An empirical model of variations in the total solar irradiance caused by observed changes in photospheric magnetic activity between 1874 and 1988 is presented. The model provides a remarkably good representation of the irradiance variations observed by satellite-borne radiometers between 1980 and 1988. It suggests that the mean total irradiance has been rising steadily since about 1945, with the largest peak so far at about 1980 and another large peak expected during the current solar cycle 22. But it is doubtful whether even this rise can contribute significantly to global warming, unless the temperature increase of about 0.02 degrees C that it produces in current energy balance models seriously underestimates the sensitivity of climate to solar irradiance changes. PMID- 17743995 TI - San salvador investigation. PMID- 17743993 TI - Art & science. PMID- 17743996 TI - Upcoming AAAS Meetings. PMID- 17743998 TI - Renewing a Scientific Society. The American Association for the Advancement of Science from World War II to 1970. Dale Wolfle. American Association for the Advancement of Science, Washington, DC, 1989. x, 337 pp. Paper, $24.95; to AAAS members, $19.95. PMID- 17743997 TI - Tracing Archaeology's Past. The Historiography of Archaeology. Andrew L. Christenson, Ed. Southern Illinois University Press, Carbondale, 1989, xii, 252 pp., illus. $29.95. Publications in Archaeology. Based on a Conference, Carbondale, IL, May 1987. PMID- 17743999 TI - Science in Sweden. The Royal Swedish Academy of Sciences, 1739-1989. Tore Frangsmyr, Ed. Science History Publications (Watson), Canton, MA, 1989. viii, 291 pp., illus. $45. PMID- 17744001 TI - RECENT ANTHROPOLOGY. PMID- 17744002 TI - RUNNING RECORDS. PMID- 17744000 TI - Products & materials. PMID- 17744004 TI - OPHTHALMOLOGICAL RESEARCH AT THE UNIVERSITY OF OXFORD. PMID- 17744003 TI - LEWELLYS F. BARKER. PMID- 17744005 TI - AIRCRAFT PRODUCTION IN GREAT BRITAIN. PMID- 17744007 TI - REHABILITATION CLINICS AT THE NEW YORK HOSPITAL. PMID- 17744006 TI - NEW FLORAS PUBLISHED BY THE NEW YORK BOTANICAL GARDEN AND THE UTAH STATE COLLEGE. PMID- 17744009 TI - A VISITING PROFESSOR TO CHINA. PMID- 17744008 TI - THE AUTUMN MEETING OF THE AMERICAN PHILOSOPHICAL SOCIETY. PMID- 17744010 TI - THE CENSUS BUREAU AND THE GREAT LAKES AREA SITUATION. PMID- 17744011 TI - SCALE CURVES IN CARTOGRAPHY. PMID- 17744013 TI - VITAMIN C FROM EVERGREENS. PMID- 17744012 TI - SPANS TWO CONTINENTS. PMID- 17744014 TI - BIOLOGICAL EFFECTS OF A TOXIC AND A SENSITIZING SUBSTANCE ISOLATED FROM PARAFFIN OIL EXTRACT OF DEAD TUBERCLE BACILLI. PMID- 17744015 TI - AN INOCULATED PENICILLIN DRESSING. PMID- 17744016 TI - AN AUTOMATIC FLOW SWITCH FOR WATER-COOLED APPARATUS. PMID- 17744017 TI - The Circulation of the Upper Troposphere and Lower Stratosphere. PMID- 17744018 TI - Some Experiments in the Freezing of Water. PMID- 17744019 TI - Internal Suberization of Plant Tissues. PMID- 17744020 TI - Effect of Coconut Milk on the Growth of Explants From Carrot Root. PMID- 17744021 TI - An Effective Depilatory Formula for Use on Laboratory Animals. PMID- 17744022 TI - The Effect of Hypertensin on the Inactivation of Oxytocin by the Serum of Pregnant Women. PMID- 17744023 TI - The Effect of Browning on the Essential Amino Acid Content of Soy Globulin. PMID- 17744024 TI - Dyes as Microchemical Indicators of a New Immunity Phenomenon Affecting a Protozoon Parasite (Toxoplasma). PMID- 17744025 TI - Propagation of Metasequoia by Juvenile Cuttings. PMID- 17744026 TI - A Note on the Fungicidal Property of Actidione. PMID- 17744027 TI - Auxin and Flower Initiation. PMID- 17744028 TI - Science and Social Problems. PMID- 17744029 TI - The Earliest Record (ca. 195 A.D.) of Fishing With the Hand. PMID- 17744030 TI - The Effects of Allyl Isothiocyanate Compared With Ultraviolet Radiation. PMID- 17744032 TI - Correction. AB - In the article on "Natural Resources Problems in Japan," by Lt. Col. Hubert G. Schenek (Science, October 8, pp. 367-372), the last sentence of paragraph 2, page 369, should read: "Production has been increased from the 1945 level of 4,000,000,000-5,000,000,000 pounds to more than 7,000,000,000 pounds which is about as much as the present fishing area can support." In the article the pounds were erroneously given in millions instead of billions. PMID- 17744031 TI - Sumner Cushing Brooks 1888-1948. PMID- 17744033 TI - Letter to the editor. PMID- 17744034 TI - Eutrophication--key elements. PMID- 17744035 TI - Remarkable crime bill. PMID- 17744036 TI - Molecular biology: peroration or obituary. PMID- 17744037 TI - Letter to the editor. PMID- 17744038 TI - Vietnam defoliation saves lives. PMID- 17744039 TI - Letter to the editor. PMID- 17744040 TI - The drinking driver. PMID- 17744041 TI - Costs versus Benefits of Increased Electric Power. PMID- 17744042 TI - The Potato: What is the botanical origin of this important crop plant, and how did it first become domesticated? PMID- 17744043 TI - AAAS Presidency: Controversy Flares over Seaborg Candidacy. PMID- 17744045 TI - 2. Arts and humanities: federal money is benefiting culture. PMID- 17744046 TI - Humanities: some typical projects. PMID- 17744047 TI - Particle track identification: application of a new technique to apollo helmets. AB - The Apollo helmets are being used to record the dose of heavy particles to which astronauts are exposed on space missions. An improved method for examining and identifying the etched tracks of heavy charged particles consists of replicating tracks and measuring the etching rate as a function of position along the track. Tracks have been observed in Apollo helmets that correspond to ionized atoms heavier than iron. PMID- 17744048 TI - Cubic FeS, a Metastable Iron Sulfide. AB - Studies of the corrosion products of metallic iron formed in the absence of air oxidation in solutions of hydrogen sulfide have revealed the existence of a new phase, cubic FeS, associated with tetragonal iron sulfide, Fe(1 + x)S. This new phase is metastable and has a sphalerite-like structure. PMID- 17744049 TI - Bottom Velocity Observations Directly under the Gulf Stream. AB - Speeds as high as 44 centimeters per second were observed 200 meters above the ocean bottom under the Gulf Stream at 70 degrees W longitude and were associated with time-dependent motion that had a speed range of 40 centimeters per second and a time scale of about 30 days. These deep current fluctuations appear to be coupled with fluctuations in the surface position of the Stream and with surface and bottom current fluctuations 200 kilometers to the north. PMID- 17744050 TI - Inversion of excited States of transition-metal complexes. AB - The nature of the emission from central metal ions in complexes can be controlled by chemical alteration of the ligands. For iridium(III) species three types of emission have been observed, each originating from a different and orbitally identifiable excited state. Principles useful for designing new luminescent materials are formulated. They can be used for guiding photochemical research and for designing new analytical methods. PMID- 17744051 TI - How did venus lose its angular momentum? AB - Venus now has a retrograde and negligible spin, but it very likely started with a typical planetary spin: prograde and with a 10- to 20-hour period. The usually assumed mechanism of solar tidal friction is quite insufficient to remove this angular momentum. Instead, we postulate capture of a moonlike object from an initially retrograde orbit: it would despin Venus and suddenly transform the planet's rotational kinetic energy into internal heat, which would lead to volcanism and the liberation of large amounts of volatiles. The moon would disappear by crashing into the surface of Venus. PMID- 17744052 TI - Celestial rotation: its importance in the development of migratory orientation. AB - Three groups of indigo buntings were hand-raised in various conditions of visual isolation from celestial cues. When they had been prevented from viewing the night sky prior to the autumn migration season, birds tested under planetarium skies were unable to select the normal migration direction. By contrast, when they had been exposed as juveniles to a normal, rotating, planetarium sky, individuals displayed typical southerly directional preferences. The third group was exposed to an incorrect planetarium sky in which the stars rotated about a fictitious axis. When tested during the autumn, these birds took up the "correct" migration direction relative to the new axis of rotation. These results fail to support the hypothesis of a "genetic star map." They suggest, instead, a maturation process in which stellar cues come to be associated with a directional reference system provided by the axis of celestial rotation. PMID- 17744053 TI - Bare Zone between California Shrub and Grassland Communities: The Role of Animals. AB - Between shrub and grass communities in coastal California there is a zone that is normally bare of vegetation. Previous studies have emphasized the role of volatile inhibitors of plant growth in producing this bare zone. However, there is a concentration of feeding activity by rodents, rabbits, and birds in this zone; if this activity is prevented by means of wire-mesh exclosures, annuals grow in the bare zone. Thus, animal activity is sufficient to produce the bare zone. PMID- 17744054 TI - Hydroxy-L-proline- and 2,2'-Dipyridyl-Induced Phenovariations in the Liverwort Nowellia curvifolia. AB - Two antagonists of "normal" proline-hydroxyproline-protein synthesis, 2,2' dipyridyl and hydroxy-L-proline, induced the same kind of phenovariation in Nowellia curvifolia (Dicks) Mitt. (Cephaloziaceae) as they do in Scapania nemorosa (Scapaniaceae). This finding supports a hypothesized cardinal role for proline-hydroxyproline-protein in modulating aspects of morphogenesis and phylogeny in the leafy liverworts. PMID- 17744055 TI - Water supply and water management problems of the great lakes. PMID- 17744056 TI - Minor metals of the geochemical environment, health and disease. PMID- 17744057 TI - Separation and depression. PMID- 17744058 TI - Problems in the meaning of death. PMID- 17744059 TI - Techniques and status of modern parapsychology. PMID- 17744060 TI - Precambrian sedimentation in the canadian shield. PMID- 17744061 TI - THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE SCIENCE AS SUBJECT-MATTER AND AS METHOD. PMID- 17744062 TI - THE FUTURE OF THE MEDICAL PROFESSION. PMID- 17744063 TI - THE NUMBER OF STUDENTS IN GERMAN UNIVERSITIES. PMID- 17744064 TI - SCIENTIFIC PUBLICATIONS FOR FREE DISTRIBUTION. PMID- 17744065 TI - LECTURES IN SANITARY SCIENCE AT COLUMBIA UNIVERSITY. PMID- 17744066 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17744067 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17744068 TI - FALL OF A METEORITE IN NORWOOD, MASSACHUSETTS. PMID- 17744070 TI - A LABORATORY ILLUSTRATION OF BALL LIGHTING. PMID- 17744069 TI - BALL LIGHTNING. PMID- 17744071 TI - THE STRICT APPLICATION OF THE LAW OF PRIORITY TO GENERIC NAMES. PMID- 17744073 TI - THE CIVILIZATION OF BOHEMIA. PMID- 17744074 TI - SCIENTIFIC JOURNALS AND ARTICLES. PMID- 17744072 TI - ENGINEERING STUDENT STATISTICS. PMID- 17744075 TI - SUMMARIES OF SIX OPINIONS (9, 11, 13, 15, 17, 18) BY THE INTERNATIONAL COMMISSION ON ZOOLOGICAL NOMENCLATURE. PMID- 17744076 TI - THE MEXICAN COTTON BOLL WEEVIL. PMID- 17744077 TI - DOUBLE IMAGES OF AN OBJECT AS SEEN THROUGH A WATER SURFACE. PMID- 17744079 TI - COMMENT AND CRITICISM. PMID- 17744078 TI - THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE SECTION A--MATHEMATICS AND ASTRONOMY. PMID- 17744080 TI - GATSCHET'S ETHNOLOGICAL MAPS OF THE GULF STATES. PMID- 17744081 TI - PARIS LETTER. PMID- 17744082 TI - EXPLORATION AND TRAVEL. PMID- 17744083 TI - ATHENS LETTER. PMID- 17744084 TI - Ethnologic results obtained upon an expedition in the south-west of the United States. PMID- 17744085 TI - Two ethnographic maps. PMID- 17744086 TI - Specific variations in the skeletons of vertebrates. PMID- 17744088 TI - International congress of geologists.--American committee meeting at Albany. PMID- 17744087 TI - LETTERS TO THE EDITOR. PMID- 17744089 TI - Barometer exposure. PMID- 17744090 TI - Instruction in natural history. PMID- 17744091 TI - The source of the Mississippi. PMID- 17744093 TI - Metric Question. PMID- 17744092 TI - The barometer during thunder-storms. PMID- 17744094 TI - A Scientist by Several Other Names. PMID- 17744095 TI - Letters to the Editor. PMID- 17744096 TI - Letters to the Editor. PMID- 17744097 TI - Drive Decay and Differential Training. PMID- 17744099 TI - Exobiology. PMID- 17744098 TI - Letters to the Editor. PMID- 17744100 TI - President Kennedy on Science. PMID- 17744101 TI - International Years of the Quiet Sun, 1964-65. PMID- 17744102 TI - Communication and Comprehension of Scientific Knowledge. PMID- 17744103 TI - John F. Kennedy: A Remembrance. PMID- 17744105 TI - Policy and Legacy. PMID- 17744104 TI - John F. Kennedy. PMID- 17744106 TI - Tritium Distribution in Ground Water around Large Underground Fusion Explosions. AB - Tritium will be released in significant amounts from large underground nuclear fusion explosions in the Plowshare Program. The tritium could become highly concentrated in nearby ground waters, and could be of equal or more importance as a possible contaminant than other long-lived fission-product and induced radionuclides. Behavior of tritiated water in particular hydrologic and geologic environments, as illustrated by hypothetical explosions in dolomite and tuff, must be carefully evaluated to predict under what conditions high groundwater concentrations of tritium might occur. PMID- 17744107 TI - Sea Level and Climate of the Past Century. AB - During the past century global temperatures increased until about 1940, after which there was a decrease. Precipitation trends show a decrease from 1900 to 1940, and a definite global increase thereafter. Sea level trends for the eastern coast of the United States are parallel to, and presumably related to, the climatological changes. PMID- 17744108 TI - Paleontologic Investigations at Big Bone Lick State Park, Kentucky: A Preliminary Report. AB - The Big Bone Lick area in Kentucky, the first widely known collecting locality for vertebrate fossils in North America, is being investigated for further faunal and geologic evidence. Mammal bones, ranging in age from Wisconsin (Tazewell?) to Recent, were recovered in 1962 from four different faunal zones in two terrace fills. PMID- 17744109 TI - Bending Waves of the Posterior Flagellum of Ceratium. AB - Flagellar bending waves, as shown by multiple-flash photomicrographs of the posterior flagellum of Ceratium, are not sine waves. The bent regions are circular arcs; these regions are separated by short segments without bending. PMID- 17744110 TI - Bipolar Planarians in a Stock Culture. AB - Four long bipolar planarians were discovered in a stock culture of asexual Dugesia dorotocephala. Such worms have not been previously reported. Eyespots, auricles, and responses to stimuli were normal in each head-end, and functional pharynges were present. Worms in the stock culture had not been subjected to temperature variations, chemicals, or other experimentation. It is suggested that the axial gradient was effectively flattened by a normal head-inhibiting factor being unable to diffuse to the posterior end. PMID- 17744112 TI - MEETING{middle dot} 26-30 DECEMBER. PMID- 17744111 TI - CLEVELAND{middle dot} 130th AAAS. PMID- 17744113 TI - Ionic Intermediates and Energy Transfer in Radiation Chemistry. PMID- 17744115 TI - BLOOD PRESSURE AND LIVER EXTRACT. PMID- 17744114 TI - Phenolics of Higher Plants. PMID- 17744117 TI - THE FORD EXHIBIT AT THE MUSEUM OF THE PEACEFUL ARTS. PMID- 17744116 TI - NEW THEORY OF LIGHT EMISSION. PMID- 17744119 TI - A NEW ANESTHETIC GAS. PMID- 17744118 TI - CHRISTMAS GREENS. PMID- 17744120 TI - BRITISH CANCER DISCOVERIES. PMID- 17744121 TI - THE AMERICAN WHEAT CROP. PMID- 17744122 TI - SOME PROBLEMS OF MEDICAL INVESTIGATION AND MEDICAL EDUCATION. PMID- 17744123 TI - THE MEETING OF THE INTERNATIONAL ASTRONOMICAL UNION. PMID- 17744125 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17744124 TI - JOHN MASON CLARKE. PMID- 17744126 TI - THE MUSIC OF THE AMERICAN INDIANS. PMID- 17744127 TI - LUMINESCENCE IN SPONGES. PMID- 17744129 TI - THE FAMILY CLIONIDAE. PMID- 17744128 TI - A METHOD OF ESTIMATING POST-GLACIAL TIME. PMID- 17744130 TI - THE SECRETION GRANULES AND THE VACUOLES IN THE LIVING THYROID GLAND. PMID- 17744131 TI - A POTATO NECROSIS RESULTING FROM CROSS-INOCULATION BETWEEN APPARENTLY HEALTHY POTATO PLANTS. PMID- 17744132 TI - FINANCIAL REPORT OF THE PACIFIC DIVISION OF THE AMERICAN ASSOCIATION. PMID- 17744133 TI - PALEONTOLOGY AS A MORPHOLOGICAL DISCIPLINE. PMID- 17744134 TI - ON PHOLADIDEA PENITA AND ITS METHOD OF BORING. PMID- 17744136 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17744135 TI - SIR JOSEPH PRESTWICH. PMID- 17744137 TI - ADAPTATIONS IN CAVE-DWELLING ANIMALS. PMID- 17744138 TI - THE OBSERVATORY OF YALE UNIVERSITY. PMID- 17744139 TI - THE EYESIGHT OF ENGLISH SCHOOL CHILDREN. PMID- 17744140 TI - COLOR PHOTOGRAPHY. PMID- 17744141 TI - THE METRIC SYSTEM. PMID- 17744142 TI - This week in science. PMID- 17744143 TI - Project 2061: a congressional view. PMID- 17744144 TI - Erratum. AB - In the report "Activation of salivary secretion: Coupling of cell volume and [Ca(2+)](i) in single cells" by J. K. Foskett and J. E. Melvin (30 June, p. 1582), figures 1 and 2 were inadvertently interchanged. The correct figures are printed below. [See Figures in source pdf.]. PMID- 17744145 TI - Computational aerodynamics for aircraft design. AB - This article outlines some of the principal issues in the development of numerical methods for the prediction of flows over aircraft and their use in the design process. These include the choice of an appropriate mathematical model, the design of shock-capturing algorithms, the treatment of complex geometric configurations, and shape modifications to optimize the aerodynamic performance. PMID- 17744146 TI - GaAs Clusters in the Quantum Size Regime: Growth on High Surface Area Silica by Molecular Beam Epitaxy. AB - Molecular beam epitaxy has been used to grow microcrystalline clusters of gallium arsenide (GaAs) in the size range from 2.5 to 60 nanometers on high-purity, amorphous silica supports. High-resolution transmission electron microscopy reveals that clusters as small as 3.5 nanometers have good crystalline order with a lattice constant equal to that of bulk GaAs. Study of the microcrystallite surfaces by x-ray photoelectron spectroscopy shows that they are covered with a shell (1.0 to 1.5 nanometers thick) of native oxides of gallium and arsenic (Ga(2)O(3) and As(2)O(3)), whose presence could explain the low luminescence efficiency of the clusters. Optical absorption spectra of the supported GaAs are consistent with the blue-shifted band edge expected for semiconductor microcrystallites in the quantum size regime. PMID- 17744147 TI - Experiments on hydraulic jumps in turbidity currents near a canyon-fan transition. AB - The point at which a submarine canyon debouches on its associated abyssal fan is generally characterized by a drop in channel slope. Turbidity currents of the kind responsible for the genesis of the canyon and fan should display an internal hydraulic jump near the slope transition. No direct field observations of any such jump appear, however, to have been made. Experiments on the nature of the jump and the resulting sedimentary deposits indicate that the thickness of the deposits just downstream of the jump tends to increase as the ratio of bed shear velocity immediately behind the jump to particle fall velocity decreases. PMID- 17744148 TI - Lignin-like compounds and sporopollenin coleochaete, an algal model for land plant ancestry. AB - Unusual cell wall structure and resistance to microbial degradation led to an investigation of resistant biopolymers in Coleochaete (Chlorophyta, class Charophyceae), a green alga on the evolutionary lineage that led to land plants. In Coleochaete that are undergoing sexual reproduction, vegetative cell walls contain material similar to lignin, a substance generally thought absent from green algae, and the zygote wall includes sporopollenin. Knowledge of chemically resistant compounds in Coleochaete may facilitate interpretation of the fossil record. Placental transfer cells in Coleochaete orbicularis and in the hornwort Anthoceros survive acetolysis and contain lignin-like compounds, implying a close relation between these taxa. PMID- 17744149 TI - Sexuality: reports from 1970: sex and morality in the u.s. PMID- 17744150 TI - Colonial adaptations: bryozoan evolution. PMID- 17744151 TI - Rifted Margins: Early Tertiary Volcanism and the Opening of the NE Atlantic. PMID- 17744152 TI - Radioactivity and health. PMID- 17744153 TI - Some other books of interest: global volcanism 1975-1985. PMID- 17744154 TI - Products & materials. PMID- 17744157 TI - PSYCHOLOGY AND THE MEDICAL SCHOOL. PMID- 17744156 TI - PHYSICAL CHEMISTRY. PMID- 17744155 TI - THE CULTURAL VALUE OF ENGINEERING EDUCATION. PMID- 17744158 TI - THE BOTANICAL WORK COMMITTEE. PMID- 17744159 TI - THE FUNCTION OF THE STATE UNIVERSITY. PMID- 17744160 TI - THE LARYNX AS AN INSTRUMENT OF MUSIC. PMID- 17744161 TI - CURRENT NOTES ON PHYSIOGRAPHY. PMID- 17744162 TI - 'IS LARVAe CONTAGIOUS?'. PMID- 17744163 TI - MUSEUM REPORTS. PMID- 17744165 TI - RAILWAY TIME TABLES BETWEEN THE EAST AND DENVER. PMID- 17744164 TI - THE AMERICAN CHEMICAL SOCIETY. PMID- 17744166 TI - Animal welfare and scientific research. PMID- 17744167 TI - Animal welfare and scientific research. PMID- 17744168 TI - On working with the soviets. PMID- 17744169 TI - Drilling, tankers, and oil spills on the atlantic outer continental shelf. PMID- 17744171 TI - Nuclear initiatives: two sides disagree on meaning of defeat. PMID- 17744170 TI - Early history of science in spanish america. PMID- 17744172 TI - Congress: election impacts atomic energy, science committees. PMID- 17744173 TI - Academy holds open hearing on research training needs. PMID- 17744174 TI - TVA Today: Former Reformers in an Era of Expensive Electricity. PMID- 17744175 TI - New medical admission test unveiled after 5 years of R & d. PMID- 17744176 TI - Viking (I): End of First Phase of 70's Space Spectacular. PMID- 17744177 TI - Hypertension: a complex disease with complex causes. PMID- 17744178 TI - Hypertension and patient noncompliance. PMID- 17744180 TI - Tours and cultural events. PMID- 17744179 TI - The 1976 nobel prize in physics. PMID- 17744182 TI - A mesoamerican site. PMID- 17744181 TI - Contributions to archeology. PMID- 17744183 TI - Marine and freshwater fungi. PMID- 17744185 TI - Pluto: evidence for methane frost. AB - Infrared photometry (1.2 to 2.2 micrometers) of Pluto provides evidence for frozen methane on the surface of the planet. This appears to be the first observational indication of this ice in the solar system. Its presence on Pluto suggests that the planet's albedo (reflectance) may be >/= 0.4 and that its diameter may be less than that of the moon. PMID- 17744184 TI - Spermatozoa. PMID- 17744186 TI - New Rules for AAAS-Newcomb Cleveland Prize. PMID- 17744187 TI - Increased transport of antarctic bottom water in the vema channel during the last ice age. AB - Particle size analyses of surface sediments in the Vema Channel reveal a spatial variation related to the present hydrography. Similar analyses of sediment deposited during the last ice age (18,000 years before the present) indicate a maximum shallowing of the upper limit of Antarctic Bottom Water (AABW) of about 100 meters, coupled with an increase in velocity, which resulted in an increase in AABW transport. PMID- 17744188 TI - Appearance of vegetation in ultraviolet light: absorbing flowers, reflecting backgrounds. AB - Flowers that uniformly absorb ultraviolet light may contrast strikingly with a bright ultraviolet-reflecting background, such as densely hairy or glaucous foliage, white soils, or the sky. Shadows will not resemble these flowers if the appearance of each in visible light is also considered. Examples are shown from Mexican heliotropiums and Michigan dune plants. PMID- 17744189 TI - Submergent macrophytes: growth under winter ice cover. AB - Densities of 26 submergent macrophyte species were determined in situ regularly for 3 years by individuals using self-contained underwater breathing apparatus (scuba). Although most of these species grew only during the summer, ten maintained high population densities and productivity throughout the winter. Maximum winter photosynthetic activity was 10 to 20 percent of summer rates. Extensive productivity of submergent aquatic plants under winter ice cover has not been well documented. PMID- 17744191 TI - Animal welfare and scientific research. PMID- 17744190 TI - Carrying behavior in humans: analysis of sex differences. AB - Behavioral differences between the sexes include methods of carrying books. Females clasp books against their chests; males carry them at their sides. In kindergarten and the first grade, both sexes carry like mature males. Sex-typical carrying appears before adolescence. Behavioral differences seem to be primarily a consequence of morphological differences and social modeling. PMID- 17744192 TI - Animal welfare and scientific research. PMID- 17744193 TI - Animal welfare and scientific research. PMID- 17744194 TI - Animal welfare and scientific research. PMID- 17744195 TI - THE WORK OF THE U. S. GEOLOGICAL SURVEY. PMID- 17744196 TI - THE GEOLOGICAL SOCIETY OF AMERICA. PMID- 17744197 TI - SEVENTH ANNUAL MEETING OF THE IOWA ACADEMY OF SCIENCE. PMID- 17744198 TI - UNUSUAL ABUNDANCE OF THE GROSBEAK IN EASTERN MASSACHUSETTS. PMID- 17744199 TI - RECENT PROGRESS IN AMERICAN HORTICULTURE. PMID- 17744200 TI - THE IMPORTANCE OF "NEXT-TO-NOTHING" IN CHEMISTRY. PMID- 17744201 TI - BREAD-FRUIT TREES IN NORTH AMERICA. PMID- 17744203 TI - Hybridism in Genus Colaptes. PMID- 17744202 TI - How Shall I Study Ants? PMID- 17744204 TI - Breathing Wells. PMID- 17744205 TI - NOTES ON MARS AND METEORS. PMID- 17744206 TI - Letters to the editor. PMID- 17744207 TI - Letters to the editor. PMID- 17744208 TI - Publishing costs. PMID- 17744209 TI - Impermanent Balance between Man and Computer. PMID- 17744210 TI - Science advice in the white house. PMID- 17744211 TI - Economists and inflation: which way out of the wilderness? PMID- 17744212 TI - Collision at the summit. PMID- 17744213 TI - New look for public works committee. PMID- 17744214 TI - NIH Cliques Assailed on Training Grants. PMID- 17744215 TI - "Transient" nuclear workers: a special case for standards. PMID- 17744216 TI - Senators seek delay in plutonium recycling. PMID- 17744217 TI - The 1974 Fields Medals (II): An Analyst and Number Theorist. PMID- 17744218 TI - Science and human health. PMID- 17744219 TI - Variations of Rayleigh Wave Phase Velocities across the Pacific Ocean. AB - Rayleigh wave phase velocities on paths crossing the Pacific Ocean show variations which are well correlated with some "average" lithospheric age of the region traversed. The seismic velocities in the upper mantle are highest in the oldest parts of the Pacific and lowest in the youngest parts. PMID- 17744220 TI - Variations of Upper Mantle Structure under the Pacific Ocean. AB - The inversion of Rayleigh wave dispersion data for the Pacific Ocean shows that lithospheric thickness increases systematically with age. The lid to the low velocity channel is very thin or absent near the ridge crest; the low-velocity channel may be absent in the oldest parts of the ocean. PMID- 17744221 TI - Asymmetric adsorption of alanine by quartz. AB - Radioactive D- and L-alanine hydrochloride in 10(-5) molar dimethylformamide solution was adsorbed by d- and 1-quartz to the extent of 20 to 30 percent, as shown by radioactivity loss. d-Quartz preferentially adsorbs D-alanine and 1 quartz adsorbs L-alanine. The extent of asymmetric preferential adsorption is about 1.0 to 1.8 percent, at the 99.9 percent confidence level. PMID- 17744224 TI - PRODUCTS and MATERIALS. PMID- 17744223 TI - Bone foreshafts from a clovis burial in southwestern montana. AB - Formal and functional analyses of bone artifacts from a Clovis burial in southwestern Montana suggest that they were constructed to serve as (detachable or nondetachable) foreshafts for attaching fluted projectile points to lance shafts. PMID- 17744222 TI - Development of the circum-antarctic current. AB - Deep-sea drilling in the Southern Ocean south of Australia and New Zealand shows that the Circum-Antarctic Current developed about 30 million years ago in the middle to late Oligocene when final separation occurred between Antarctica and the continental South Tasman Rise. Australia had commenced drifting northward from Antarctica 20 million years before this. PMID- 17744226 TI - THE NEW YORK ZOOLOGICAL SOCIETY. PMID- 17744225 TI - DETERMINISM AND RESPONSIBILITY. PMID- 17744227 TI - STEPHEN WALTER RANSON 1880-1942. PMID- 17744228 TI - HERBERT CLIFTON HAMILTON 1868-1942. PMID- 17744229 TI - NEW HABITAT GROUPS OF THE AMERICAN MUSEUM OF NATURAL HISTORY. PMID- 17744230 TI - THE ROYAL OBSERVATORY AT THE CAPE OF GOOD HOPE. PMID- 17744231 TI - THE NAVY COLLEGE TRAINING PROGRAM. PMID- 17744233 TI - THE COPERNICAN QUADRICENTENNIAL. PMID- 17744232 TI - THE NUTRITION FOUNDATION. PMID- 17744234 TI - WAR WORK IN THE HIGH SCHOOLS. PMID- 17744235 TI - HALOGETON GLOMERATUS, POISONOUS TO SHEEP. PMID- 17744236 TI - OCCURRENCE OF THE PLIOCENE ANTELOPE, ILINGOCEROS, IN NEVADA. PMID- 17744238 TI - ON THE CELLULAR DIVISION OF SPACE WITH MINIMUM AREA. PMID- 17744237 TI - INCREASED SYNTHESIS OF p-AMINOBENZOIC ACID ASSOCIATED WITH THE DEVELOPMENT OF SULFONAMIDE RESISTANCE IN STAPHYLOCOCCUS AUREUS. AB - Sulfonamide-resistant strains of Staphylococcus aureus produce greater amounts of p-aminobenzoic acid than do their parent strains. This synthesis occurs both in the absence and in the presence of sulfonamides. The quantity of p-aminobenzoic acid synthesized by resistant strains appears sufficient to account for their resistance to sulfonamide drugs. On the basis of this evidence, it is suggested that the development of ability to synthesize p-aminobenzoic acid in excess of the normal metabolic requirements, as a result of continued exposure to sulfonamides, explains the phenomenon of sulfonamide fastness in Staphylococcus aureus. PMID- 17744239 TI - AN APPLICATION OF THE CONTROL CHART METHOD TO THE ANALYSIS OF FISHERIES DATA. PMID- 17744240 TI - This week in SCIENCE. PMID- 17744241 TI - Technology for America's Future. PMID- 17744242 TI - Energy savings. PMID- 17744244 TI - Response. PMID- 17744243 TI - Energy savings. PMID- 17744245 TI - Math problems. PMID- 17744246 TI - Math problems. PMID- 17744247 TI - Math problems. PMID- 17744248 TI - Math problems. PMID- 17744249 TI - Science in the persian gulf. PMID- 17744250 TI - Sciencescope. PMID- 17744252 TI - Science academy elects new members. PMID- 17744251 TI - Science under wraps in prince william sound. PMID- 17744254 TI - A billion bucks for materials. PMID- 17744253 TI - Congressional day. PMID- 17744255 TI - A big gift from big oil. PMID- 17744256 TI - Hidden costs of the space station. PMID- 17744257 TI - Engineering dogma gives way to chaos. PMID- 17744258 TI - Flying high with chaos control. PMID- 17744260 TI - Praying mantises play top gun. PMID- 17744259 TI - A new ball game in nuclear physics. PMID- 17744261 TI - Deep rocks stir the mantle pot. PMID- 17744262 TI - Geometry, topology, and universality of random surfaces. AB - Previous simulations of a self-avoiding, closed random surface with restricted topology (without handles) on a three-dimensional lattice have shown that its behavior on long length scales is consistent with that of a branched-polymer. It is shown analytically that such a surface with an unrestricted number of handles has a qualitatively different geometry and therefore is in a different universality class. The effect of a net external pressure is to suppress the handles and collapse the surface into a branched polymer-like configuration. Topology is thus shown to be a key factor in determining the universality class of the system. PMID- 17744263 TI - Ultradeep (>300 kilometers) ultramafic xenoliths: petrological evidence from the transition zone. AB - The seismologically delineated transition zone, at depths between 400 and 670 kilometers, is a fundamental discontinuity in the earth that separates the upper mantle from the lower mantle. Xenoliths from within or close to the transition zone are dominated by pyropic garnet and associated pyroxene or mineralogically heterogeneous garnet lherzolite. These xenoliths show evidence for the high pressure (90 to 120 kilobars) transformation of pyroxene to a solid solution of pyroxene in garnet (majorite) and silicon in octahedral coordination; low pressure (less than 80 kilobars) exsolution of clinopyroxene or orthopyroxene from the original majorite is preserved. Although mineral modes and rock proportions below the transition zone and the relative amount of eclogite present cannot be accurately assessed from the xenoliths, it is likely that both majorite and beta-spinel help produce the observed seismic gradient of the transition zone. PMID- 17744264 TI - Response. PMID- 17744265 TI - Land plants and weathering. PMID- 17744266 TI - Chemistry regenerated. PMID- 17744268 TI - Weatherwatchers. PMID- 17744267 TI - An emergent field. PMID- 17744269 TI - Products & materials. PMID- 17744270 TI - THE SPHERE OF THE UNITED STATES GEOLOGICAL SURVEY. PMID- 17744271 TI - IMPROVEMENT OF THE NATIVE PASTURE-LANDS OF THE FAR WEST. PMID- 17744273 TI - THE HEAD-HUNTERS OF BORNEO. PMID- 17744272 TI - HISTORY OF THE APPLICATION OF THE ELECTRIC LIGHT TO LIGHTING THE COASTS OF FRANCE. PMID- 17744274 TI - GEOLOGICAL MAP OF BELGIUM. PMID- 17744275 TI - Peculiar faulting of a coal-bed. PMID- 17744277 TI - Flight of the flying-fish. PMID- 17744276 TI - Use of wire in sounding. PMID- 17744278 TI - WHITNEY'S CLIMATIC CHANGES. PMID- 17744279 TI - Sand-tracery. PMID- 17744280 TI - The Leadville porphyry. PMID- 17744281 TI - DEEP-SEA MEDUSAE. PMID- 17744282 TI - Public views of scientists. PMID- 17744283 TI - Information and the ecology of scholars. AB - Groups of scholars often behave in ways that are startlingly reminiscent of the behavior of groups of plants and animals in a biological ecosystem. I have tried to show that the parallel may have its basis in two fundamental considerations: (i) the similar properties of stable dissipative structures in a wide variety of contexts and (ii) the mathematical similarity of information to chemical (nutrient) free energy. A particularly intriguing problem is that of successional trends arising from the kinetic limitation of information flow through the intellectual and social structures created by scholars. The "strategy of ecosystem development" may have implications for the strategy of academic administration. In this connection, it is worth bearing in mind Marglef's dictum (6, p. 77): "Probably the hypothesis holds everywhere that the less mature ecosystem feeds the more mature structures around it." PMID- 17744284 TI - Psychology: clinicians seek professional autonomy. PMID- 17744285 TI - Council of U.S. Academy of Sciences Expresses Concern to Soviet Counterparts over Sakharov Harrassment. AB - National Academy of Sciences (NAS) president Philip Handler has made public a cable to his opposite number in the Soviet Union expressing the "deep concern" of the NAS Council for the welfare of dissenting Soviet physicist Andrei Sakharov and warning that, if further measures were taken against Sakharov, "it would be extremely difficult to imagine successful fulfillment of American pledges of binational scientific cooperation . . . ." Handler's message is the strongest public expression to date of NAS concern over treatment of Soviet scientists and other intellectuals (Science, 6 April). The cable, addressed to M. V. Keldysh, president of the Soviet Academy of Sciences, is given in full below. PMID- 17744287 TI - Congress and executive: expanding an adversary relationship. PMID- 17744286 TI - The Health of U.S. Science: NSB Says the Prognosis Is Guarded. PMID- 17744289 TI - Cosmology: the first large radio red shift. PMID- 17744288 TI - Quasars: are they near or far, young galaxies or not? PMID- 17744290 TI - Tropical cyclone bebe creates a new land formation on funafuti atoll. AB - A huge rubble rampart 18 kilometers long was formed at Funafuti Atoll during tropical cyclone Bebe on 21 October 1972. The material forming the rampart was derived from deeper water offshore. The formation appears to be permanent and indicates that tropical storms may play a significant role in the formation of atoll islets. PMID- 17744292 TI - National Science Youth Month. PMID- 17744291 TI - Pressure dependence of the radioactive decay constant of beryllium-7. AB - Diamond anvil presses of a new design were used to compress samples of beryllium 7 oxide to 120, 210, and 270 kilobars. The decay constant for the conversion of beryllium-7 to lithium-7 by electron capture was measured for compressed and uncompressed samples. A least-squares fit of the equation (lambda(c) lambda)/lambda = KpP to the experimental data, where lambda(C) and lambda are the decay constants of the compressed sample and an uncompressed sample, respectively, and P is pressure, yields a value of (2.2 +/- 0.1) x 10(-5) kbar( 1) for the constant K(p). PMID- 17744293 TI - Radioactivity of Potassium and Geologic Time. PMID- 17744295 TI - Erratum. AB - The recent obituary notice for Ward Evans [Science 349, 126 (23 Aug. 1957)] contains the inaccurate statement that he was the "lone member of the Atomic Energy Commission's special three-man Personal Security Board of 1954 who ruled that J. R. Oppenheimer was a loyal citizen." It is correct that Evans was the only member of the board who recommended that Oppenheimer should retain his security clearance; however, the majority report affirmed emphatically the belief that Oppenheimer was a loyal citizen and pointed out his eminent services to his country. PMID- 17744294 TI - News of Science. PMID- 17744296 TI - "Atom Bomb Effect"--Recent Increase of Carbon-14 Content of the Atmosphere and Biosphere. PMID- 17744297 TI - Binding of Histamine and Antihistamine to Bovine Serum Albumin by Mediation with Cu(II). PMID- 17744298 TI - Meetings and Societies. PMID- 17744299 TI - EQUIPMENT NEWS. PMID- 17744300 TI - The Horse's Mouth. PMID- 17744302 TI - News of Science. PMID- 17744301 TI - University of Arizona Radiocarbon Dates. PMID- 17744304 TI - Amino Acid Factor in Control of Abscission. PMID- 17744303 TI - Erratum. AB - On page 1173 of the 6 December issue of Science, it was stated incorrectly that Floyd H. Allport is professor emeritus at the University of Oregon. He is professor emeritus at Syracuse University. PMID- 17744305 TI - Role of Parenchyma Cells in Graft Union in Vanilla Orchid. PMID- 17744306 TI - Meetings and Societies. PMID- 17744307 TI - THE MATHEMATICAL THEORY OF THE TOP. PMID- 17744308 TI - THE TRANSMISSION OF RADIANT HEAT BY GASES AT VARYING PRESSURES. PMID- 17744310 TI - THE ANNIVERSARY MEETING OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17744309 TI - THE BREEDING OF ANIMALS AT WOODS HOLL DURING THE MONTH OF MARCH, 1898. PMID- 17744311 TI - CURRENT NOTES ON PHYSIOGRAPHY. PMID- 17744312 TI - NOTES ON INORGANIC CHEMISTRY. PMID- 17744313 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17744315 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17744314 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17744316 TI - SCIENTIFIC JOURNALS. PMID- 17744317 TI - URANIUM AND GEOLOGY--II. PMID- 17744318 TI - REPORT OF THE INTERNATIONAL CONFERENCE ON ELECTRICAL UNITS AND STANDARDS, 1908. PMID- 17744320 TI - THE CONVOCATION WEEK MEETING OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE AND AFFILIATED SOCIETIES. PMID- 17744319 TI - OTIS TUFTON MASON. PMID- 17744321 TI - THE HAYDEN MEMORIAL MEDAL. PMID- 17744322 TI - SIDE ISSUES BEARING ON THE AGE OF NIAGARA FALLS. PMID- 17744323 TI - THE QUESTION OF PROFESSORS' SALARIES. PMID- 17744324 TI - BOTANICAL NOTES. PMID- 17744325 TI - MENDELIAN HEREDITY. PMID- 17744326 TI - THE OTTER IN MASSACHUSETTS. PMID- 17744328 TI - News of Science. PMID- 17744327 TI - To the Barricades? PMID- 17744329 TI - W. R. Brode, President Elect. PMID- 17744330 TI - Reports of Sections and Societies, New York Meeting. PMID- 17744331 TI - Meetings and Societies. PMID- 17744332 TI - Gross National Product. PMID- 17744333 TI - Deep-Sea Diving Record. PMID- 17744334 TI - About Meriones. PMID- 17744335 TI - Gross National Product. PMID- 17744336 TI - SCIENCE NEWS. PMID- 17744337 TI - EARTH ROTATION AND RIVER EROSION. PMID- 17744338 TI - THE NOBEL PRIZE IN PHYSIOLOGY AND MEDICINE FOR 1932. PMID- 17744339 TI - GEOLOGY--AN EASIER STUDY FOR BOYS OR FOR GIRLS? PMID- 17744340 TI - RADIO STUDIES DURING THE LEONID METEOR SHOWER OF NOVEMBER 16, 1932. PMID- 17744342 TI - FERROUS IODIDE AND LINOLEIC ACID IN VITAMIN A DEFICIENCY. A REPLY TO CERTAIN CRITICISMS. PMID- 17744341 TI - THE ACTIVATION OF UREASE. PMID- 17744343 TI - PROBLEMS OF POPULATION. PMID- 17744345 TI - WORK OF THE ROCKEFELLER FOUNDATION. PMID- 17744344 TI - THE PAINTED DESERT. PMID- 17744346 TI - SYMPOSIA AT ATLANTIC CITY. PMID- 17744348 TI - MOVING PICTURE FILM ADAPTER FOR ROLL FILM CAMERAS. PMID- 17744347 TI - A GLASS ELECTRODE FOR TESTING THE pH OF BLOOD. PMID- 17744349 TI - AN EFFECT OF THE RECENT SOLAR ECLIPSE ON THE IONIZED LAYERS OF THE UPPER ATMOSPHERE. PMID- 17744351 TI - THE STABILITY OF FUNCTIONALLY DISTINCT RACES OF FIBROBLASTS. PMID- 17744350 TI - ON THE PREPARATION OF HEMOLYTIC AND PRECIPITATING SERA. PMID- 17744352 TI - CONTROL OF THE BLOSSOM BLIGHT STAGE OF FIRE BLIGHT. PMID- 17744354 TI - Monitoring of atmospheric ozone. PMID- 17744353 TI - Federal and trade deficits. PMID- 17744355 TI - Radar's Growing Vulnerability: As weapons become smarter, they learn to "see" radar beams as pathways to their target, gaining an advantage over defensive systems. PMID- 17744356 TI - UC Told to Review Impact of Research. PMID- 17744357 TI - DOE Undermines Own Nonproliferation Effort: The department is trying to persuade other countries to move away from highly enriched uranium in research reactors but is planning a reactor of its own that will use the material. PMID- 17744358 TI - Hot Dry Rock: Problems, Promise: After a decade of hard lessons and limited success, tapping the enormous heat reserves in rock too dry to yield steam or hot water on its own faces more challenges. PMID- 17744359 TI - Coral Bleaching Threatens Atlantic Reefs: Unexplained changes are occurring in some of the most productive ecosystems on the planet, the Caribbean coral reefs. PMID- 17744360 TI - End-cretaceous mass extinction event: argument for terrestrial causation. AB - The end-Cretaceous mass extinctions were not a geologically instantaneous event and were selective in character. These features are incompatible with the original Alvarez hypothesis of their being caused by a single asteroid impact that produced a world-embracing dust cloud with devastating environmental consequences. By analysis of physical and chemical evidence from the stratigraphic record it is shown that a modified extraterrestrial model in which stepwise extinctions resulted from encounter with a comet shower is less plausible than one intrinsic to the earth, involving significant disturbance in the mantle. PMID- 17744361 TI - Icosahedral solids: a new phase of matter? AB - Numerous examples of metallic alloys have been discovered, the atomic structures of which display an icosahedral symmetry that is impossible for ordinary periodic crystals. Recent experimental results support the hypothesis that the alloys are examples of a new "quasicrystal" phase of solid matter. Observed deviations from an ideal quasicrystal structure can be explained as "phason strains," a special class of defects predicted to be the dominant type of imperfection formed during solidification. PMID- 17744362 TI - Antarctic stratospheric chemistry of chlorine nitrate, hydrogen chloride, and ice: release of active chlorine. AB - The reaction rate between atmospheric hydrogen chloride (HCl) and chlorine nitrate (ClONO(2)) is greatly enhanced in the presence of ice particles; HCl dissolves readily into ice, and the collisional reaction probability for ClONO(2) on the surface of ice with HCl in the mole fraction range from approximately 0.003 to 0.010 is in the range from approximately 0.05 to 0.1 for temperatures near 200 K. Chlorine (Cl(2)) is released into the gas phase on a time scale of at most a few milliseconds, whereas nitric acid (HNO(3)), the other product, remains in the condensed phase. This reaction could play an important role in explaining the observed depletion of ozone over Antarctica; it releases photolytically active chlorine from its most abundant reservoir species, and it promotes the formation of HNO(3) and thus removes nitrogen dioxide (NO(2)) from the gas phase. Hence it establishes the necessary conditions for the efficient catalytic destruction of ozone by halogenated free radicals. In the absence of HCl, ClONO(2) also reacts irreversibly with ice with a collision efficiency of approximately 0.02 at 200 K; the product hypochlorous acid (HOCI) is released to the gas phase on a time scale of minutes. PMID- 17744363 TI - Reaction of chlorine nitrate with hydrogen chloride and water at antarctic stratospheric temperatures. AB - Laboratory studies of heterogeneous reactions important for ozone depletion over Antarctica are reported. The reaction of chlorine nitrate (ClONO(2)) with H(2)0 and hydrogen chloride (HCl) on surfaces that simulate polar stratospheric clouds [ice and nitric acid (HNO(3))-ice and sulfuric acid] are studied at temperatures relevant to the Antarctic stratosphere. The reaction of ClONO(2) on ice and certain mixtures of HNO(3) and ice proceeded readily. The sticking coefficient of ClONO(2) on ice of 0.009 +/- 0.002 was observed. A reaction produced gas-phase hypochlorous acid (HOCl) and condensed-phase HNO(3); HOC1 underwent a secondary reaction on ice producing dichlorine monoxide (Cl(2)O). In addition to the reaction with H(2)0, ClONO(2) reacted with HCl on ice to form gas-phase chlorine (Cl(2)) and condensed-phase HNO(3.) Essentially all of the HCl in the bulk of the ice can react with ClONO(2) on the ice surface. The gaseous products of the above reactions, HOCl, Cl(2)0, and Cl(2), could readily photolyze in the Antarctic spring to produce active chlorine for ozone depletion. Furthermore, the formation of condensed-phase HNO(3) could serve as a sink for odd nitrogen species that would otherwise scavenge the active chlorine. PMID- 17744364 TI - Spacelab-2 plasma depletion experiments for ionospheric and radio astronomical studies. AB - The Spacelab-2 Plasma Depletion Experiments were a series of studies to examine shuttle-induced perturbations in the ionosphere and their application to ground based radio astronomy. The space shuttle Challenger fired its orbital maneuvering subsystem engines on 30 July and 5 August 1985, releasing large amounts of exhaust molecules (water, hydrogen, and carbon dioxide) that caused the electrons and ions in Earth's upper atmosphere to chemically recombine, thereby creating so called "ionospheric holes." Two burns conducted over New England produced ionospheric peak depletions ranging from 25 to 50 percent, affected the ionosphere over a 200-kilometer altitude range, and covered 1 degrees to 2 degrees of latitude. Optical emissions associated with the hole spanned an area of several hundred thousand square kilometers. A third burn was conducted over a low-frequency radio observatory in Hobart, Australia, to create an "artificial window" for ground-based observations at frequencies normally below the natural ionospheric cutoff (penetration) frequency. The Hobart experiment succeeded in making high-resolution observations at 1.7 megahertz through the induced ionospheric hole. PMID- 17744365 TI - White light sunspot observations from the solar optical universal polarimeter on spacelab-2. AB - The flight of the Solar Optical Universal Polarimeter on Spacelab-2 provided the opportunity for the collection of time sequences of diffraction-limited (0.5 are second) solar images with excellent pointing stability (0.003 are second) and with freedom from the distortion that plagues ground-based images. A series of white-light images of active region 4682 were obtained on 5 August 1985, and the area containing the sunspot has been analyzed. These data have been digitally processed to remove noise and to separate waves from low-velocity material motions. The results include (i) proper motion measurements of a radial outflow in the photospheric granulation pattern just outside the penumbra; (ii) discovery of occasional bright structures ("streakers") that appear to be ejected outward from the penumbra; (iii) broad dark "clouds" moving outward in the penumbra, in addition to the well-known bright penumbral grains moving inward; (iv) apparent extensions and contractions of penumbral filaments over the photosphere; and (v) observation of a faint bubble or looplike structure that seems to expand from two bright penumbral filaments into the photosphere. PMID- 17744366 TI - Ultraviolet observations of solar fine structure. AB - The High Resolution Telescope and Spectrograph was flown on the Spacelab-2 shuttle mission to perform extended observations of the solar chromosphere and transition zone at high spatial and temporal resolution. Ultraviolet spectroheliograms show the temporal development of macrospicules at the solar limb. The C IV transition zone emission is produced in discrete emission elements that must be composed of exceedingly fine (less than 70 kilometers) subresolution structures. PMID- 17744367 TI - Diel periodicity of photosynthesis in polar phytoplankton: influence on primary production. AB - In the Southern Ocean, primary production estimated from seasonal chemical and geochemical changes is two to four times greater than the value calculated from carbon-14 uptake. Since carbon uptake had typically been measured only during midday incubations, the influence of diel periodicity of photosynthesis on daily productions was not considered. Phytoplankton from McMurdo Sound, Antarctica, exhibited distinct, but seasonally variable diel patterns of light-saturated and light-limited photosynthesis. Maximum photosynthetic capacity occurred about noon in early September, and its occurrence progressively shifted to about midnight by late October. This shift was accompanied by a concomitant phase shift in the occurrence of minimum photosynthetic capacity from midnight to midday. Daily production estimated from time-of-day corrected photosynthetic characteristics and from 24-hour incubations was 2.5 to 4 times greater than that predicted from 6-hour midday incubations. If similar diel periodicity in photosynthesis occurs in other polar oceans, primary production would be significantly higher than previously estimated from carbon-14 uptake measurements. PMID- 17744368 TI - Debates involving science: scientific controversies. PMID- 17744369 TI - Plant-water relations: stomatal function. PMID- 17744371 TI - Products & materials. PMID- 17744370 TI - Landform studies from space: geomorphology from space. PMID- 17744372 TI - Cost of research. PMID- 17744374 TI - Newton and mercury poisoning. PMID- 17744373 TI - Cost of research. PMID- 17744375 TI - Future planetary missions. PMID- 17744376 TI - Cost of research. PMID- 17744377 TI - Erratum. AB - In the report "Selective protection of methionine enkephalin released from brain slices by enkephalinase inhibition" by G. Patey et al. (5 June, p. 1153), Fig. 1B was labeled incorrectly. The corrected figure is printed below. PMID- 17744379 TI - Giant geoduck. PMID- 17744378 TI - Trace elements. PMID- 17744380 TI - Giant geoduck. PMID- 17744381 TI - Giant geoduck. PMID- 17744382 TI - R & d at bell laboratories. PMID- 17744383 TI - Hurricane Allen's Impact on Jamaican Coral Reefs. AB - Coral reefs of north Jamaica, normally sheltered, were severely damaged by Hurricane Allen, the strongest Caribbean hurricane of this century. Immediate studies were made at Discovery Bay, where reef populations were already known in some detail. Data are presented to show how damage varied with the position and orientation of the substraturn and with the shape, size, and mechanical properties of exposed organisms. Data collected over succeeding weeks showed striking differences in the ability of organisms to heal and survive. PMID- 17744384 TI - Colonization lessons from a tropical forest. AB - The decade-old Transamazon Highway provides a useful stage for examining some of the major issues related to frontier conquest and the impact of pioneer settlement on one of the world's richest biomes. The highway project is an ambitious colonization scheme and the lessons that can be drawn from it, ranging from the environmental effects of stripping back the tree cover to the spread of diseases, will be useful in guiding development policy in other tropical regions. PMID- 17744385 TI - Reactor safety and the research budget. PMID- 17744386 TI - Physicists Give ISABELLE a Yes, But . . PMID- 17744387 TI - Acid rain bills reflect regional dispute. PMID- 17744388 TI - IOM Counsels Secret Service. PMID- 17744389 TI - Computer data banks: the delights and dangers. PMID- 17744390 TI - New mistakes uncovered at diablo canyon reactors. PMID- 17744391 TI - Peace commission calls for federal establishment. PMID- 17744392 TI - Weak creationist bill filed in Maryland. PMID- 17744393 TI - Cornell submicron facility dedicated. PMID- 17744394 TI - Building knowledge and understanding: enduring assets of society. PMID- 17744395 TI - History of the calculus. PMID- 17744396 TI - Social interests and statistical theory. PMID- 17744397 TI - Conceptions of space. PMID- 17744398 TI - Gene duplication. PMID- 17744399 TI - A botanical garden. PMID- 17744400 TI - A framework for systematics. PMID- 17744401 TI - A gel partition model for organic desorption from a pond sediment. AB - Adsorption at the water-sediment interface has been correlated with the organic carbon content of natural sediment samples and with water-octanol partitioning equilibria. In deriving a new model for sorption in sediment, it is assumed that adsorption is due to humin-kerogen polymers associated with the clay component in the sediment. The model includes solubility parameter theory applied to solute gel-liquid interactions and a theory of the liquid-polymer interactions that control gel swelling. Partially swollen gels are expected to exhibit impeded diffusion. These concepts are able to explain observations of limited desorption of certain organic compounds from natural sediments and soil minerals. Experiments were performed in which extractive solvents flowed through a liquid chromatographic column packed with dried estuarine and pond sediment samples and the effluent was analyzed for a test lipophilic compound, di(2-ethylhexyl) phthalate. The model predicts that the maximum desorption rate and the maximum extent of gel swelling should coincide and, conversely, that the desorption rate should be diffusion-limited if the polymer gel is only partially swollen. The conditions for maximum desorption and for diffusion-limited desorption were both observed experimentally. PMID- 17744402 TI - Lamellar twinning explains the nearly racemic composition of chiral, single crystals of hexahelicene. AB - Solvent etching of single crystals of hexahelicene grown from a racemic solution reveals an unusual layer-like pattern in which pure (+)- and pure (-)-layers alternate through the crystal; this arrangement results in a nearly racemic composition although the crystal is ostensibly chiral, space group P2(1)2(1)2(1). Etched crystals of enantiomerically pure hexahelicene display no such pattern. The two kinds of crystal are indistinguishable by x-ray diffraction. PMID- 17744403 TI - Competition between ant species: outcome controlled by parasitic flies. AB - Experimental evidence demonstrates that the parasitic phorid fly Apocephalus shifts the competitive balance between the ant species Pheidole dentata and Solenopsis texana by interfering with the defensive behavior of Pheidole dentata major workers (soldiers). This represents one of the first examples of a parasite affecting competitive interactions anmong terrestrial animals in natural communities. Similar complex interactions are probably common in many ant communities. PMID- 17744404 TI - Early experience determines song dialect responsiveness of female sparrows. AB - In a laboratory experiment, female white-crowned sparrows responded almost exclusively to male songs taken from their home dialect region and usually not to songs taken from an alien dialect region. Song dialect populations may represent a level of genetic population structure below that of the subspecies and may play an important role in songbird evolution. PMID- 17744405 TI - PRODUCTS and MATERIALS. PMID- 17744406 TI - Better Nothing Than Something? PMID- 17744408 TI - The Kefauver Hearings: The Drug Industry Finally Has Its Day and Does Quite Well. PMID- 17744407 TI - The Competitive World of the Pure Scientist: The quest for prestige can cause conflict between the goals of science and the goals of the scientist. PMID- 17744409 TI - Population Boom: Administration Presents a Policy Statement That Is Ingeniously Confusing. PMID- 17744410 TI - Civil Defense: Like It or Not, Believe in It or Not, the Program Will Soon Be a Reality. PMID- 17744411 TI - Air Pollution: Auto Industry Bows to Ultimatum. PMID- 17744412 TI - Ratio of Thorium-230 to Thorium-232 in Deep-Sea Sediments. AB - The ionium-thorium method for age determination in deep-sea sediments is critically reviewed, and its shortcomings are discussed. A method that allows an estimate of the rate of sedimentation in the superficial layer of the sediment is presented. A formula for calculating the error in age determination by the method is given for the case when the rate of sedimentation is changing and, with it, the rate of thorium-232 sedimentation. PMID- 17744413 TI - International Geophysical Calendar for 1962. AB - Coordination of certain types of geophysical observations and analyses throughout the world is accomplished by the advance selection of days and intervals for such work. A committee under the International Council of Scientific Unions has issued the calendar for 1962, together with a brief explanation and examples of how it may be used in planning geophysical programs. PMID- 17744415 TI - Forthcoming Events. PMID- 17744414 TI - Hydra: Workers from many fields consider the physiology and ultrastructure of hydra and other coelenterates. PMID- 17744416 TI - THE AMERICAN ASSOCIATION OF INVENTORS AND MANUFACTURERS. PMID- 17744417 TI - SOME RECENT MINERAL DISCOVERIES IN THE STATE OF WASHINGTON. PMID- 17744418 TI - THE EVOLUTION OF THE LOUP RIVERS IN NEBRASKA. PMID- 17744419 TI - A RECENT ANALYSIS OF WILL. PMID- 17744421 TI - STRUCTURE OF THE TRACHEAe OF INSECTS. PMID- 17744420 TI - SIR GEORGE BIDDELL AIRY. PMID- 17744422 TI - Some Curious Catnip Leaves. PMID- 17744423 TI - Rain-Making by Faith. PMID- 17744424 TI - Traumatic Hypnotism. PMID- 17744426 TI - THE GEOLOGY OF GOVERNMENT EXPLORATIONS. PMID- 17744425 TI - A Lightning Stroke. PMID- 17744427 TI - PHASES IN JAMAICAN NATURAL HISTORY. PMID- 17744429 TI - A PROPOSED BUREAU OF PLANT REGISTRATION. PMID- 17744428 TI - THE INTERNATIONAL METEOROLOGICAL AND HYDROLOGICAL MEETINGS. PMID- 17744430 TI - CURRENT NOTES ON PHYSIOGRAPHY. PMID- 17744431 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17744432 TI - VAN BENEDEN AND THE ORIGIN OF THE CENTROSOME.--A CORRECTION. PMID- 17744433 TI - A TEST ON DIVERSITY OF OPINION. PMID- 17744434 TI - THE VELOCITY OF A FLIGHT OF DUCKS OBTAINED BY TRIANGULATION. PMID- 17744435 TI - Philip Hauge Abelson, New Editor of "Science". PMID- 17744436 TI - Atomic Power: House Decides That "Sweetened" Proposal for Using Hanford Steam Is Still Unpalatable. PMID- 17744437 TI - NIH Administration: Congress Told It Will Tighten Up. PMID- 17744439 TI - Goethite in Radular Teeth of Recent Marine Gastropods. AB - The x-ray diffraction patterns of the denticle material from several species show that the material consists of the mineral goethite. This is the first indication that goethite is precipitated by marine invertebrates. The mineralogy of the denticle caps has biologic and geologic implications. PMID- 17744438 TI - Wiesner Confirmed To Head New Science Office. AB - The Senate last week unanimously approved the nomination of Jerome B. Wiesner as director of the newly established Office of Science and Technology. Wiesner's nomination occasioned his first formal appearance before a Congressional committee since he joined the administration as K,ennedy's special assistant for science and technology. He retains that post while serving as director of the new office and will also continue as chairman of the President's Science Advisory Committee (PSAC), an 18-member group of nongovernmental consultants drawn from science, industry, and education. He will also continue as chairman of the Federal Council on Science and Technology, which is the intra-governmental counterpart of the PSAC. In relations between science and government Wiesner probably occupies the most influential position in the country. Following are excerpts from his testimony before the Senate Labor and Public Welfare Committee. (A limited number of complete transcripts may be obtained without charge from the committee at Room 4230, New Senate Office Building, Washington, D.C.). PMID- 17744440 TI - Animals Used as Food by Late Archaic and Woodland Cultural Groups in New England. AB - Remains of vertebrates and invertebrates found at several New England Woodland sites confirmed results and conclusions of earlier investigators, and further indicated that amphibians and reptiles were not used much as food, if so used at all. Vertebrate remains found at Late Archaic sites indicate the presence of a largely contemporary fauna. Failure of Late Archaic people at sites studied to use mollusks in quantity as food may have been determined by cultural barriers, and not by lack of availability. PMID- 17744441 TI - Speleology: Peculiar laboratories for the study of evolution, caves fascinate scientists from many disciplines. PMID- 17744442 TI - Forthcoming Events. PMID- 17744443 TI - IS THERE A SENSE OF DIRECTION? PMID- 17744444 TI - CURRENT NOTES ON ANTHROPOLOGY.--XIII. PMID- 17744445 TI - SOME POINTS IN THE NOMENCLATURE-PRIORITY QUESTION. PMID- 17744446 TI - THE PROGRESS MADE IN TEACHING DEAFS CHILDREN TO READ LIPS AND TALK, IN THE UNITED STATES AND CANADA. PMID- 17744447 TI - REMARKS ON NORTH AMERICAN LICHENOLOGIY.--PRELIMINARY. PMID- 17744449 TI - The Fundamental Hypotheses of Abstract Dynamics. PMID- 17744448 TI - Does There Really Exist a Phonetic Key to the Maya Hieroglyphic Writing? PMID- 17744450 TI - Hectoring a Hawk. PMID- 17744451 TI - The Black-Knot. PMID- 17744452 TI - The Brutal Dove. PMID- 17744454 TI - This week in science. PMID- 17744453 TI - Tornado-Whirls in the Upper Clouds. PMID- 17744455 TI - The international geosphere-biosphere program. PMID- 17744456 TI - Atmospheric carbon dioxide and summer soil wetness. PMID- 17744457 TI - Response:the funding of science. PMID- 17744459 TI - The funding of science. PMID- 17744458 TI - The funding of science. PMID- 17744460 TI - Artist identified. PMID- 17744461 TI - Response:atmospheric carbon dioxide and summer soil wetness. PMID- 17744462 TI - The Pentagon Is Not Eating Engineers: Contrary to conventional wisdom, a report for the Academy of Engineering finds no evidence that the defense buildup is draining talent from the civil sector. PMID- 17744463 TI - Mathematicians Look to SDI for Research Funds: A briefing organized by the National Academy of Sciences provided an opportunity for mathematicians to make a pitch for SDI money. PMID- 17744465 TI - Plate Tectonics Is the Key to the Distant Past: Field geologists taking a closer look at 3-billion-year-old rocks are deciding that drifting plates formed them after all. PMID- 17744464 TI - Comings and goings. PMID- 17744467 TI - Frontiers of neuroscience. PMID- 17744466 TI - The 1986 Nobel Prize In Chemistry: The award honors three pioneers in the field of chemical reaction dynamics; their work has given rise to chemical lasers and offers the possibility of precisely guiding reactions. PMID- 17744468 TI - Changing climate: geothermal evidence from permafrost in the alaskan arctic. AB - Temperature profiles measured in permafrost in northernmost Alaska usually have anomalous curvature in the upper 100 meters or so. When analyzed by heat conduction theory, the profiles indicate a variable but widespread secular warming of the permafrost surface, generally in the range of 2 to 4 Celsius degrees during the last few decades to a century. Although details of the climatic change cannot be resolved with existing data, there is little doubt of its general magnitude and timing; alternative explanations are limited by the fact that heat transfer in cold permafrost is exclusively by conduction. Since models of greenhouse warming predict climatic change will be greatest in the Arctic and might already be in progress, it is prudent to attempt to understand the rapidly changing thermal regime in this region. PMID- 17744469 TI - Life cycle, individual thrift, and the wealth of nations. AB - One theory of the determinants of individual and national thrift has come to be known as the life cycle hypothesis of saving. The state of the art on the eve of the formulation of the hypothesis some 30 years ago is reviewed. Then the theoretical foundations of the model in its original formulation and later amendment are set forth, calling attention to various implications, some distinctive to it and some counterintuitive. A number of crucial empirical tests, both at the individual and the aggregate level, are presented as well as some applications of the life cycle hypothesis of saving to current policy issues. PMID- 17744470 TI - Regular intervals between hawaiian earthquakes: implications for predicting the next event. AB - During the years 1941 through 1983 five earthquake mainshocks of moderate magnitude occurred at regular intervals of 10.5 +/- 1.5 years within a 6 kilometer radius in Hawaii. It is proposed that these Kaoiki earthquakes will continue to occur at regular intervals because the strain accumulation rate and the strained volume remain constant. With appropriate instrumentation, it may be possible to refine predictions of subsequent Kaoiki earthquakes. PMID- 17744471 TI - Report Details AAAS Response to "Crisis in Science Education". PMID- 17744472 TI - Obituaries. PMID- 17744473 TI - New issue dates of science. PMID- 17744474 TI - Project updating directory of scientist and engineers with disabilities. PMID- 17744475 TI - Science and security: the future of arms control. PMID- 17744476 TI - Issues of public service: universities and state governments. PMID- 17744477 TI - Professions in america: professional powers. PMID- 17744478 TI - Aquatic plants: phytoplankton ecology. PMID- 17744479 TI - Bioenergetics extended: the vital force. PMID- 17744481 TI - THE ROMANCE OF THE NEXT DECIMAL PLACE. PMID- 17744480 TI - Products & materials. PMID- 17744483 TI - SCIENCE NEWS. PMID- 17744482 TI - RESEARCH AND INDUSTRIAL ORGANIC CHEMISTRY. PMID- 17744484 TI - TWISTING IN LOWER FORMS OF PLANTS. PMID- 17744485 TI - METEORITES IN SEDIMENTARY ROCKS? PMID- 17744486 TI - POSSIBLE RELATION OF AGE AT SEXUAL MATURITY IN BIRDS TO DAILY PERIOD, INTENSITY AND WAVELENGTH OF LIGHT. PMID- 17744487 TI - NATURALLY DEPOSITED EGGS OF THE MYXINOIDEA (HYPEROTRETIA). PMID- 17744489 TI - SCIENCE BOOKLETS FROM THE AMERICAN ASSOCIATION. PMID- 17744490 TI - SEDIMENTATION AND SEDIMENTOLOGY. PMID- 17744488 TI - "ENTAMOEBA" PHALLUSIAE. PMID- 17744492 TI - MUSEUM TAGS OF CHEMICAL PROOF PAPER. PMID- 17744491 TI - CULTURAL AND INOCULATION METHODS WITH TILLETIA SPECIES. PMID- 17744493 TI - A THERMOPHIL NITRITE FORMER. PMID- 17744494 TI - THE DISTRIBUTION OF EXTRA-GALACTIC NEBULAE. PMID- 17744495 TI - THE HEMOGLOBIN CONTENT OF THE BLOOD OF THE HEN: A STATISTICAL STUDY OF INFLUENCES AND RELATIONS. PMID- 17744496 TI - THE ADMINISTRATION OF AGRICULTURAL RESEARCH. PMID- 17744497 TI - RESOLUTIONS ADOPTED AT THE AUSTRALIAN MEETING OF THE PACIFIC SCIENCE CONGRESS. PMID- 17744498 TI - THE FRIENDS OF MEDICAL PROGRESS. PMID- 17744499 TI - JOHN THOMAS GULICK, MISSIONARY AND DARWINIAN. PMID- 17744501 TI - HAEMATOXYLIN. PMID- 17744500 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17744502 TI - EINSTEIN AND SOLDNER. PMID- 17744504 TI - THE EFFECT OF FORMALDEHYDE UPON THE VITAMIN CONTENT OF MILK. PMID- 17744503 TI - FISHES FALLEN FROM THE SKY. PMID- 17744505 TI - AMERICAN MATHEMATICAL SOCIETY. PMID- 17744506 TI - THE WORK OF A BOTANICAL LABORATORY IN PHARMACEUTICAL MANUFACTURE. PMID- 17744507 TI - ON THE EMERENGENCE OF A SHAM BIOLOGY IN AMERICA. PMID- 17744508 TI - THE AURORA. PMID- 17744509 TI - THE PREFIX AQ-IN KITONAQA. PMID- 17744511 TI - MAMMOTH CAVE IN MARCH. PMID- 17744510 TI - EARTHQUAKES IN AUSTRALASIA. PMID- 17744513 TI - Prehistoric Coil Pottery. PMID- 17744512 TI - Anatomical Nomenclature. PMID- 17744514 TI - The Neanderthal Skull. PMID- 17744515 TI - Probable Causes of Rainy Period in Southern Peru. PMID- 17744516 TI - The Results of Search for Paleolithic Implements in the Ohio Valley. PMID- 17744517 TI - The Sense of Boundary in Dogs. PMID- 17744518 TI - Singing of Birds. PMID- 17744519 TI - Speech of Children. PMID- 17744520 TI - A Peculiar Eye. PMID- 17744521 TI - THE NERVOUS SYSTEM. PMID- 17744522 TI - SUMMARY STATEMENT OF THE WORK OF THE NATIONAL RESEARCH COUNCIL. PMID- 17744523 TI - SIGNIFICANT FIGURES IN STATISTICAL CONSTANTS. PMID- 17744524 TI - PARAMECIUM MULTIMICRONUCLEATA VS. PARAMECIUM MULTIMICRONUCLEATUM. PMID- 17744525 TI - THE ULTRACENTRIFUGAL CONCENTRATION OF PNEUMOCOCCIC ANTIBODIES. PMID- 17744526 TI - WANTED: A NEW WORD. PMID- 17744527 TI - TROCHOSPONGILLA HORRIDA IN ARKANSAS. PMID- 17744528 TI - EARTH WORMS AS TEST OBJECTS FOR DETERMINING THE VALUE OF DRUGS TO BE USED IN HUMAN INTESTINAL HELMINTH INFESTATIONS. PMID- 17744529 TI - THE CONDENSATION OF beta-CYCLOCITRAL WITH DIMETHYLACROLEIN. PMID- 17744530 TI - CATALYSIS OF FORMALDEHYDE TO REDUCING SUGARS BY ASCORBIC ACID. PMID- 17744531 TI - THE REGAL LILY AS A SOURCE OF ROOT-TIP MATERIAL. PMID- 17744532 TI - A Simple Laboratory-Made Blast Lamp. PMID- 17744534 TI - Tax incentives and research. PMID- 17744533 TI - A SIMPLE DEVICE FOR SHORT PHOTOGRAPHIC EXPOSURES. PMID- 17744535 TI - Internal solitons in the andaman sea. AB - The solitary wave is a localized hydrodynamic phenomenon that can occur because of a balance between nonlinear cohesive and linear dispersive forces in a fluid. It has been shown theoretically, and observed experimentally, that some solitary waves have properties analogous to those of elementary particles, and the waves have therefore been named solitons. During a measurement program in the Andaman Sea near northern Sumatra, large-amplitude, long internal waves were observed with associated surface waves called tide rips. Using theoretical results from the physics of nonlinear waves, it is shown that the internal waves are solitons and their interactions with surface waves are described. PMID- 17744536 TI - Oils and rubber from arid land plants. AB - In this article the economic development potentials of Cucurbita species (buffalo gourd and others), Simmondsia chinensis (jojoba), Euphorbia lathyris (gopher plant), and Parthenium argentatum (guayule) are discussed. All of these plants may become important sources of oils or rubber. PMID- 17744537 TI - Materials science. PMID- 17744538 TI - Use of killer weed grows in third world. PMID- 17744539 TI - Fund for UN Science Center Short by $200 Million. PMID- 17744540 TI - Environmentalists seek new strategies. PMID- 17744541 TI - Nonproliferation policy challenged. PMID- 17744542 TI - Maryland lures chip-makers East. PMID- 17744543 TI - Giant corporations from tiny chips grow. PMID- 17744544 TI - A new kind of storm beneath the sea. PMID- 17744545 TI - Nuclear arms control group named. PMID- 17744546 TI - Climate project to produce research guide. PMID- 17744547 TI - CSFR Reports Activities. PMID- 17744548 TI - Note to AAAS Members. PMID- 17744549 TI - Research and bulletins on science and technology for the handicapped. PMID- 17744550 TI - Chautauqua short courses. PMID- 17744551 TI - About section x-general. PMID- 17744552 TI - Science 80 growth. PMID- 17744553 TI - Working together: science and the law. PMID- 17744554 TI - Paleobiogeography: current concerns. PMID- 17744555 TI - Space physics. PMID- 17744557 TI - Planetary geochemistry. PMID- 17744556 TI - Ecological mosaic. PMID- 17744558 TI - Developmental biology. PMID- 17744559 TI - Radiant heat for energy conservation. AB - It is proposed that human comfort could be provided in otherwise chilly surroundings by filling the occupied space with electromagnetic energy of centimeter wavelength. Very considerable reductions in the consumption of energy required for the heating of buildings should result from the lowering of interior temperatures thereby permitted. PMID- 17744560 TI - The double quasar 0957+561: examination of the gravitational lens hypothesis using the very large array. AB - A full 12-hour synthesis at 6-centimeter wavelength with the Very Large Array confirms the major features previously reported for the double quasar 0957+561. In addition, the existence of radio jets apparently associated with both quasars is demonstrated. Gravitational lens models are now favored on the basis of recent optical observations, and the radio jets place severe constraints on such models. Further radio observations of the double quasar are needed to establish the expected relative time delay in variations between the images. PMID- 17744561 TI - Evaporation of seawater: calculated mineral sequences. AB - Van't Hoff's predictions of the mineral sequences to be expected on the evaporation of seawater are based on an oversimplified system. New computer calculation that include calcium-bearing phases are in better agreement with natural occurrences, removing discrepancies that have plagued evaporite geologists for nearly a century. A new hydrologic model that combines equilibrium batch evaporation with fractionation between successive batches is proposed to account for the mineral sequences observed in such classic deposits as the German Zechstein. PMID- 17744562 TI - Selenium biomethylation products from soil and sewage sludge. AB - Inorganic selenium compounds are converted to volatile methylated species (dimethyl selenide, dimethyl diselenide, and dimethyl selenone or methyl methylselenite) by microorganisms in sewage sludge and soil. In the absence of added selenium, no volatile selenium compounds were detected. All samples were evaluated without the addition of nutrients and in the presence of air or nitrogen. The methylation process may be an important step in the detoxification process for microorganisms exposed to high concentrations of selenium. PMID- 17744563 TI - Miocene deposits in the amazonian foreland basin. PMID- 17744565 TI - Response: miocene deposits in the amazonian foreland basin. PMID- 17744564 TI - Miocene deposits in the amazonian foreland basin. PMID- 17744566 TI - KHAM-I-AB. PMID- 17744567 TI - DR. ROMANES ON PHYSIOLOGICAL SELECTION. PMID- 17744568 TI - PACIFIC COAST WEATHER. PMID- 17744569 TI - LAUNHARDT'S MATHEMATICAL ECONOMICS. PMID- 17744570 TI - THE POPULATION OF MEDIAEVAL CITIES. PMID- 17744571 TI - ON RECENT PROGRESS TOWARD THE SOLUTION OF PROBLEMS IN HYDRODYNAMICS. PMID- 17744572 TI - BOTANY AT THE ANNIVERSARY MEETING OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17744573 TI - ACTA OF THE INTERNATIONAL CONFERENCE ON SCIENTIFIC LITERATURE. PMID- 17744574 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17744575 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17744576 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17744577 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17744579 TI - ON A SUITABLE NAME FOR THE NEW PLANET. PMID- 17744578 TI - DISCUSSION AND CORRESPONDENCE. PMID- 17744580 TI - THE STRESS-STRAIN RELATIONS OF RUBBER. PMID- 17744581 TI - THE MINOR PLANET DQ. PMID- 17744582 TI - THE SENSE OF SOLIDITY. PMID- 17744583 TI - THE ENDOWMENT OF AMERICAN ARCHAeOLOGY. PMID- 17744584 TI - THE LOWER SONORAN COCHINEAL. PMID- 17744585 TI - THE PASADENA MEETING OF THE PACIFIC DIVISION. PMID- 17744587 TI - THE ROYAL COLLEGE OF SURGEONS. PMID- 17744586 TI - ERHARD FERNHOLZ. PMID- 17744588 TI - AWARD TO THE BAUSCH AND LOMB OPTICAL COMPANY. PMID- 17744589 TI - EXPEDITIONS OF THE AMERICAN MUSEUM OF NATURAL HISTORY. PMID- 17744590 TI - DEFENSE TRAINING COURSES OF COLLEGE GRADE. PMID- 17744591 TI - RESEARCH IN INDUSTRY. PMID- 17744592 TI - ILLUSIONS IN PRINTED MATTER. PMID- 17744594 TI - DESIGNATION OF LOCATIONS ON MAPS. PMID- 17744593 TI - INTERNATIONAL COOPERATION. PMID- 17744595 TI - AWARD OF GUGGENHEIM FELLOWSHIPS FOR 1941. PMID- 17744596 TI - THE ORIGIN OF THE RETE APPARATUS IN THE OPOSSUM. PMID- 17744597 TI - THE INDUCTION OF FERTILITY IN GENETICALLY SELF-STERILE PLANTS. PMID- 17744598 TI - ARGINASE. PMID- 17744599 TI - A NEW PROCEDURE FOR ADSORPTION ANALYSIS. PMID- 17744600 TI - Gerontocracy. PMID- 17744601 TI - The worlds of reflection and action. PMID- 17744602 TI - Isotopic paleotemperatures. PMID- 17744603 TI - Three-dimensional map construction. AB - Three-dimensional maps are useful tools which have been neglected for some time. They shouldbe more commonly used, and familiarity with the techniques discussed in this article should dispel any qualms anyone might ve about needing artistic talent to nstruct them. The saving in time esulting from the use of an anamorphoser provides a further incentive. The anamorphoser transformations discussed above were all prepared by using straight slits, oriented at right angles to each other and placed so that all planes of the elements were parallel to each other. It is possible to vary these conditions in an infinite number of ways and thereby produce nonparallel tranceformations. Some of these variations are illustrated in Fig. 10. All the illustrations in Fig. 10 are transformations of the planimetric weather map shown in Fig. 8A. The variations used for the maps of Fig. 10 are as follows. (A) All planes parallel, with a curved rear slit; (B) all planes parallel, with curved slits front and rear; ( C) all planes parallel, with S-shaped rear slit; (D) all planes parallel, with an undulating rear slit; (E) all planes parallel, with curved front and undulating rear slit; (F) plane of the original rotated on the horizontal axis-both slits curved; (G) plane of the original rotated on thevertical axis- both slits curved; (H) plane of the original rotated on the horizontal axis -both slits straight. These are only a few of the many transformations which can be made with an anamorphoser, butthey do point toward some interesting possibilities. For example, it appears that maps based onone projection might be altered to satisfy the coordinates of a completely different projection. Note, for example, the change of parallels from concave to convex curves (Figs. 8A and 10A) and the change from converging meridians to diverging meridians (Figs. 8A and l0G). Similarly, the grids of maps B, F, and H of Fig. 10 approximate projections which are quite different from the original. Other possible, and noncartographic, uses also come to mind. For example, transformations offront and side views of architectural and engineering drawings could be made to show views fromdifferent elevations and orientations. Or a geologist might be able to illustrate folding of sedimentary strata by preparing a drawing of a series of horizontal beds and then using an anamo rephoser with an undulating slit to alter the beds to any degree of folding desired. With a movie camera and a moving lens mount this "folding" process could be photographed with different settings, so that the parallel beds would gradually and continuously change to irregularly folded beds. The transformations shown in Fig. 10 resulted from uncontrolled experimentation with the anamorphoser, and as yet no geometric solutions for setting up the transformation elements are available. Similarly, the suggested uses are mere flights of fancy, and no claim is made for theirpracticality. It is hoped, however, that they will stimulate the reader's imagination and lead him to look for uses of the anamorphoser in fields other than cartography (9). PMID- 17744605 TI - University of montreal: where the two canadas meet. PMID- 17744604 TI - Development of quantum electrodynamics. PMID- 17744606 TI - "Hindsight": DOD Study Examines Return on Investment in Research. PMID- 17744607 TI - Sediment Movement on the Continental Shelf near Washington and Oregon. AB - The nuclides zinc-65 and cobalt-60 associated with river-borne particulate matter are incorporated in sediment on the Continental Shelf near the Colum- ia River. Changes in the relative concentrations of zinc-65 and cobalt-60 and in the ratio of the activity of zinc-65 and cobalt-60 suggest that radioactive sediment moves northward 12 to 30 kilometers per year along the shelf and 2.5 to 10 kilometers per year westward away from the coast. PMID- 17744608 TI - Pacific pleistocene cores: faunal analyses and geochronology. AB - Two cores from the eastern Pacific were analyzed faunally and dated by the ionium: thorium method. Comparison of the results of these and of similar studies of Atlantic cores indicate that faunal changes, representing changes between the glacial and interglacial stages of the Pleistocene, occurred in both oceans simultaneously. PMID- 17744609 TI - Absence of neutral alkali atoms in rhodizite. AB - The formula CsB(l2)Be(4)Al(4)O(28) has been proposed by others for the mineral rhodizite. Electron-spin-resonance and magnetic susceptibility measurements prove the absence of neutral cesium atoms. An ionic formula CsB(11)Be(4)Al(4)O(26)(OH)(2) is proposed. PMID- 17744610 TI - Beach Cusps: Response to Plateau's Rule? PMID- 17744611 TI - Molybdenum diselenide: rhombohedral high pressure-high temperature polymorph. AB - A three-layered rhombohedral form of molybdenum diselenide has been produced by subjecting the normal two-layered hexagonal form to pressures of 40 kilobars and temperatures of 1500 degrees C. The new form is isostructural with rhombohedral molybdenum disulfide. PMID- 17744612 TI - Nucleotide formation as a determinant of 5-Fluorouracil response in mouse leukemias. AB - Survival of mice bearing different transplantable leukemias and treated with 5 fluorouracil was compared with accumulation of drug nucleotides in vitro. There was significant correlation,suggesting that cellular capacity for conversion of the drug to nucleotides is a major determinant of inherent drug sensitivity of these leukemias. PMID- 17744613 TI - Desert Tortoise Gopherus agassizii: Cutaneous Water Loss. AB - Evaporative water loss from the integument of the desert tortoise Gopherus agassizii constitutes a major proportion of the water loss, but is far less than in tortoises from wetter regions. Respiratory water loss also is less. PMID- 17744614 TI - Forthcoming events. PMID- 17744615 TI - SCIENCE NEWS. PMID- 17744616 TI - CERTAIN ASPECTS OF GEOLOGIC CLASSIFICATIONS AND CORRELATIONS. PMID- 17744617 TI - UPTHRUST--A GEOLOGIC TERM. PMID- 17744618 TI - ALTERATIONS IN THE FOUNDATIONS OF THE EXACT SCIENCES IN MODERN TIMES. PMID- 17744619 TI - FURTHER COMMENTS ON THE TRIHYDROL CONTROVERSY. PMID- 17744620 TI - APPROPRIATIONS FOR GRANTS-IN-AID BY THE NATIONAL RESEARCH COUNCIL. PMID- 17744621 TI - THE CHICAGO SOIL-NUTRIENT-TEMPERATURE TANK. PMID- 17744622 TI - REGULATING THE FLOW OF SOLUTION FOR PLANT CULTURES. PMID- 17744623 TI - THE ROLE OF THE CARBAMINO COMPOUNDS IN THE TRANSPORT OF CO2 BY THE BLOOD. PMID- 17744624 TI - REFRACTORINESS TO OVARIAN STIMULATION IN THE RHESUS MONKEY. PMID- 17744625 TI - THE CONTROL OF BRONCHIAL ASTHMA. PMID- 17744627 TI - FLOOD PREVENTION AND ITS RELATION TO THE NATION'S FOOD SUPPLY. PMID- 17744626 TI - EDUCATIONAL COSTS. PMID- 17744628 TI - A NOTABLE BOTANICAL CAREER. PMID- 17744629 TI - THE LASSEN ERUPTION. PMID- 17744630 TI - M. ALBERT LACROIX. PMID- 17744631 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17744632 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17744633 TI - THE CONFERRING OF THE BACHELOR'S DEGREE UPON NON-GRADUATES. PMID- 17744634 TI - MULTIPLE FACTORS VS. "GOLDEN MEAN" IN SIZE INHERITANCE. PMID- 17744635 TI - DISAGREEMENTS IN CHEMICAL NOMENCLATURE. PMID- 17744636 TI - THE GOLDEN MEAN. PMID- 17744638 TI - EIGHTH LIST OF GENERIC NAMES (MAMMALS) UNDER CONSIDERATION IN CONNECTION WITH THE OFFICIAL LIST OF ZOOLOGICAL NAMES. PMID- 17744637 TI - THE PROFESSOR AND THE INSTITUTION. PMID- 17744639 TI - THE IONE FORMATION OF THE SIERRA NEVADA FOOTHILLS, A LOCAL FACIES OF THE UPPER TEJON-EOCENE. PMID- 17744640 TI - THE INCREASE IN PERMEABILITY OF THE FROG'S EGG AT THE BEGINNING OF DEVELOPMENT AND THE PRESERVATION OF THE LIFE OF THE EGG. PMID- 17744642 TI - Tougher competition in teaching. PMID- 17744641 TI - THE AMERICAN CHEMICAL SOCIETY. III. PMID- 17744643 TI - Are grades necessary? PMID- 17744644 TI - Ceramics today. PMID- 17744645 TI - Defense research: questions for Vietnam dissenters. PMID- 17744646 TI - Making of a president: stanford students decry lack of voice. PMID- 17744647 TI - Radiation bleaching of thin lunar surface layer. AB - The thin, lighter-colored, upper layer of lunar soil shown in the television pictures from several Surveyor missions may be due to reversible bleaching by solar radiation. Of several possible bleaching reactions, the one considered most important is the photoreduction of Fe(+3) to Fe(+2). PMID- 17744648 TI - Transform faulting and growth of the gulf of california since the late pliocene. AB - Seismic-reflection and magnetic profiles over more than 6000 kilometers suggest that spreading of the sea floor on the East Pacific Rise, at the mouth of the Gulf of California, began to broaden a proto-gulf about 4 million years ago. Movement occurred, on transform faults, offsetting the rise and other centers of crustal growth within the gulf, and translated the end of the peninsula about 200 kilometers to the northwest. Thick pelagic sediments on the east flank of the rise indicate that there was a lapse of spreading by crustal growth between 4 and 10 million years ago. PMID- 17744649 TI - Calcium supply to plant roots. AB - Direct observations of the calcium-45 distribution around the roots of plants growing in soil showed a pattern in direct contrast to that predicted from calculations based on the calcium concentration of the soil solution, transpiration rates, and plant calcium content. Whereas calcium-45 accumulation at the root surface was predicted, depletion was observed. It is suggested that preferential water movement in larger pores may decrease the expected solution calcium accumulation at the root surface. However, autoradiographs may give no indication of soil solution concentration depletion or accumulation because of the relatively high level on the colloid surface. The nature and extent of the depletion indicates how profoundly the plant root alters its immediate environment in the soil. PMID- 17744650 TI - ON THE AMPLITUDE OF VIBRATION OF ATOMS. PMID- 17744651 TI - MARSH'S ODONTORNITHES. PMID- 17744652 TI - ON THE SOUTHERN STARS AND OTHER CELESTIAL OBJECTS. PMID- 17744654 TI - THE GLYCERINE BAROMETER. PMID- 17744653 TI - ASTRONOMY. PMID- 17744655 TI - MICROSCOPES. PMID- 17744656 TI - Erratum. AB - In the letter "Nuclear test yields" by Jack F. Evernden and Lynn R. Sykes (17 Feb., p. 642), the symbol for surface wave magnitudes was incorrectly given as m(b) in line 39 of the second column of page 644. The correct symbol is m(s). PMID- 17744657 TI - Illmensee inquiry. PMID- 17744658 TI - Nuclear winter scenario. PMID- 17744659 TI - Juarez radiation accident. PMID- 17744660 TI - Juarez radiation accident. PMID- 17744661 TI - U.s. Withdrawal from unesco. PMID- 17744662 TI - Amending the national science foundation act. PMID- 17744663 TI - New laser source technology. AB - Over the past 5 to 8 years several new laser sources have been developed as a result of R & D efforts stimulated by a growing number of laser applications. Four families of new devices-semiconductor diod laser arrays, free electron lasers, rare gas halide excimer sources, and several new tunable solid-state lasers-show particular promise. PMID- 17744664 TI - Scientists and congress. AB - Scientists are urged to make their views known to members of Congress. To be effectively heard, they should establish personal contact with their congressmen and senators and their staff. Communication should be frequent, personal, and carefully focused. In the last 2(1/2) years, federal funding of scientific research has been severely cut back, while military research funding has been increased. The selection process for funding research is being politicized. Scientists should concern themselves with what is happening politically because the quality of American scientific research is being threatened. PMID- 17744665 TI - Iraq's Chemical Warfare: Case Proved: A U.N. team found mustard and nerve gas bombs on the battlefield; now the challenge is to prevent the war from spreading. PMID- 17744666 TI - Pentagon names star wars czar. PMID- 17744667 TI - Universities gag on research controls. PMID- 17744668 TI - Will Deficits Put a Damper on R & D?: Ninth AAAS Colloquium on R & D worries about looming budgetary gaps, asks if some new initiatives are too much of a good thing. PMID- 17744669 TI - Pressure for patent reform. PMID- 17744670 TI - Meselson meets a shower of yellow rain from bees. PMID- 17744671 TI - Computing in the Language of Science: Computer programs are too difficult to read and to modify, says physicist Kenneth Wilson, who is devising a better way. PMID- 17744673 TI - A New Route to Chiral Compounds: Hydroboration of olefins with a derivative of agr-pinene produces chiral intermediates that can be converted into many other compounds. PMID- 17744672 TI - Ice Cap of 30 Million Years Ago Detected: The oxygen isotopes of marine sediments are providing strong indirect evidence of an Antarctic ice cap twice as ancient as the present one. PMID- 17744674 TI - Hot atoms: fundamental processes in energetic atomic collisions. PMID- 17744676 TI - Sedimentary particles: coated grains. PMID- 17744675 TI - Supernova remnants: supernova remnants and their x-ray emission. PMID- 17744677 TI - Primate morphometrics: the order of man. PMID- 17744678 TI - Helium-3 emission related to volcanic activity. PMID- 17744679 TI - Early eocene vertebrates from baja california: evidence for intracontinental age correlations. AB - Newly discovered fossils support a Wasatchian (early Eocene) age for the Punta Prieta vertebrate fauna of Baja California and reveal the utility of land mammal ages on a continental scale. Dispersal scenarios for late Paleocene and early Eocene vertebrates usually invoke heterochrony for similar, but geographically separated, faunas or taxa. Such heterochrony is not supported by independent geochronologies or adequate geographic samples. PMID- 17744680 TI - Topography from single radar images. AB - A mathematical theory and a corresponding numerical procedure have been developed to produce digital topography from radar images as digital photometric arrays. Thus, as radargrammetry is to photogrammetry, so radarclinometry is to photoclinometry. Photoclinometry encompasses a fundamental indeterminacy principle even for terrain that is homogeneous in normal albedo, because the surface normal consistent with a given reflected specific intensity is not unique. A geometric locus of such normal directions is implied, which generates a surface. For microwave backscatter, in specific application to radarclinometry, this surface is a cone whose half-angle is the incidence angle, whose axis contains the radar, and whose apex coincides with the terrain point. Although the indeterminacy can be removed if a properly directed profile of ground truth is available as a constraint, such is seldom the case. In its absence, an auxiliary assumption, such as that the strike line runs perpendicular to the illumination line, is needed. If metric integrity is a goal, then this is an absurd assumption. Herein, "the hypothesis of local cylindricity" has been assumed, a premise regarding the nature of topographic curvature that seems more realistic and that makes possible the production of topography as a set of parallel line integrals. PMID- 17744681 TI - Gaseous nitrate radical: possible nighttime atmospheric sink for biogenic organic compounds. AB - The gaseous nitrate (NO(3)) radical, which has recently been measured in nighttime ambient atmospheres over the United States and Europe at concentrations up to approximately 350 parts per trillion, has now been shown to react rapidly with the biogenically emitted organic compounds dimethyl sulfide (DMS), isoprene, and several monoterpenes. Computer simulations demonstrate that these reactions can dominate the atmospheric behavior of these organic compounds at night. Thus reaction with NO(3) radicals may be the unknown, nonphotochemical removal process for DMS recently invoked by Andreae and Raemdonck to explain the absence of a diurnal profile for DMS in maritime air influenced by continental air masses. Similarly, the nighttime reaction of NO(3) radicals with monoterpenes can be a dominant removal process, leading to very low monoterpene concentrations in ambient atmospheres during the early morning. PMID- 17744682 TI - High incidence of "leapfrog" pattern of geographic variation in andean birds: implications for the speciation process. AB - Many species of birds in the humid forests of the Andes show a pattern of geographic variation in color that is virtually unknown in other regions of the world. This pattern, here termed "leapfrog," is one in which two populations very similar in appearance are geographically separated from each other by very different, intervening populations of the same species. Approximately 21 percent of all Andean bird species and superspecies with three or more differentiated populations show the leapfrog pattern, and several of these show multiple cases of leapfrogging color patterns. Lack of concordance in the geographic distribution of taxa showing the leapfrog pattern suggests that there is a strongly random component in phenotypic differentiation with respect to direction, geography, and timing. PMID- 17744683 TI - Arctic biostratigraphic heterochroneity. PMID- 17744684 TI - Arctic biostratigraphic heterochroneity. PMID- 17744685 TI - Arctic biostratigraphic heterochroneity. PMID- 17744686 TI - THE ROYAL SOCIETY OF CANADA. PMID- 17744687 TI - THE INTERNATIONAL FISHERIES EXHIBITION.--SECOND PAPER. PMID- 17744688 TI - RECENT DEEP-SEA SOUNDINGS OFF THE ATLANTIC COAST OF THE UNITED STATES. PMID- 17744689 TI - THE PROTOZOAN PARASITES OF THE OYSTER. PMID- 17744690 TI - THE USE OF STEEL SOUNDING-WIRE BY LIEUT. J. C. WALSH, U.S N., ON THE TANEY, IN 1849-50. PMID- 17744691 TI - CHEMICAL AND PHYSIOLOGICAL RESEARCHES ON THE PTOMAINES. PMID- 17744692 TI - LAKE BONNEVILLE. PMID- 17744694 TI - Fish-hooks from southern California. PMID- 17744693 TI - Precocity in a chicken. PMID- 17744695 TI - Lake Superior geology. PMID- 17744696 TI - THE GRAPE PHYLLOXERA IN FRANCE. PMID- 17744697 TI - Impregnation in the turkey. PMID- 17744698 TI - Intelligence of the crow. PMID- 17744700 TI - INTELLIGENCE FROM AMERICAN SCIENTIFIC STATIONS. PMID- 17744699 TI - CALIFORNIA AGRICULTURE. PMID- 17744701 TI - This week in science. PMID- 17744702 TI - Science education: who needs it? PMID- 17744703 TI - Dinosaur diversity and extinction. PMID- 17744704 TI - Magnetic storm predictions. PMID- 17744705 TI - Response. PMID- 17744706 TI - Dinosaur diversity and extinction. PMID- 17744707 TI - Corrections and clarifications. AB - In the report "Transcription factor loading on the MMTV promoter: A biomodal mechanism for promoter activation" by T. K. Archer et al. (20 Mar., p. 1573), the sentence in the legend to figure 2 (p. 1574) which indicated treatment or lack of treatment with hormone should have read, "Samples in lanes 1, 2, 5, and 7 represent DNA from untreated cells, and samples in lanes 3, 4, 6, and 8 represent DNA from cells treated with hormone." PMID- 17744709 TI - Lots of possible solutions, little progress. PMID- 17744708 TI - New Mexico: technology-rich. PMID- 17744710 TI - California evolution defender indicted. PMID- 17744711 TI - Merci-a new mersenne prime. PMID- 17744712 TI - Top 10 universities in chemistry. PMID- 17744713 TI - FAUST Blows a Fuse. PMID- 17744714 TI - Cluster fusion: close, but no cigar. PMID- 17744715 TI - Could a pair of cosmic strings open a route into the past? PMID- 17744716 TI - CERN's New Detectors Take Shape. PMID- 17744717 TI - Mantle plumes and continental tectonics. AB - Mantle plumes and plate tectonics, the result of two distinct modes of convection within the Earth, operate largely independently. Although plumes are secondary in terms of heat transport, they have probably played an important role in continental geology. A new plume starts with a large spherical head that can cause uplift and flood basalt volcanism, and may be responsible for regional scale metamorphism or crustal melting and varying amounts of crustal extension. Plume heads are followed by narrow tails that give rise to the familiar hot-spot tracks. The cumulative effect of processes associated with tail volcanism may also significantly affect continental crust. PMID- 17744718 TI - Hybridization of bird species. AB - Hybridization, the interbreeding of species, provides favorable conditions for major and rapid evolution to occur. In birds it is widespread. Approximately one in ten species is known to hybridize, and the true global incidence is likely to be much higher. A longitudinal study of Darwin's finch populations on a Galapagos island shows that hybrids exhibit higher fitness than the parental species over several years. Hybrids may be at an occasional disadvantage for ecological rather than genetic reasons in this climatically fluctuating environment. Hybridization presents challenges to the reconstruction of phylogenies, formulation of biological species concepts and definitions, and the practice of biological conservation. PMID- 17744719 TI - A new type of meteoritic diamond in the enstatite chondrite abee. AB - Diamonds with delta(13)C values of -2 per mil and less than 50 parts per million (by mass) nitrogen have been isolated from the Abee enstatite chondrite by the same procedure used for concentrating Cdelta, the putative interstellar diamond found ubiquitously in primitive meteorites and characterized by delta(13)C values of -32 to -38 per mil, nitrogen concentrations of 2,000 to 12,500 parts per million, and delta(15)N values of -340 per mil. Because the Abee diamonds have typical solar system isotopic compositions for carbon, nitrogen, and xenon, they are presumably nebular in origin rather than presolar. Their discovery in an unshocked meteorite eliminates the possibility of origins normally invoked to account for diamonds in ureilites and iron meteorites and suggests a low-pressure synthesis. The diamond crystals are approximately 100 nanometers in size, are of an unusual lath shape, and represent approximately 100 parts per million of Abee by mass. PMID- 17744720 TI - An SCF Solvation Model for the Hydrophobic Effect and Absolute Free Energies of Aqueous Solvation. AB - A model for absolute free energies of solvation of organic, small inorganic, and biological molecules in aqueous solution is described. This model has the following features: (i) the solute charge distribution is described by distributed monopoles, and solute screening of dielectric polarization is treated with no restrictions on solute shape; (ii) the energetic effects of cavity formation, dispersion interactions, and solute-induced restructuring of water are included by a semiempirical cavity surface tension; and (iii) both of these effects are included in the solute Hamiltonian operator for self-consistent field (SCF) calculations to allow solvent-induced electronic and geometric distortion of the solute. The model is parameterized for solutes composed of H, C, N, O, F, P, S, Cl, Br, and I against experimental data for 150 neutral solutes and 28 ions, with mean absolute errors of 0.7 and 2.6 kilocalories per mole, respectively. PMID- 17744721 TI - Thermal equilibration during cavitation. PMID- 17744722 TI - AIDS in a new mode. PMID- 17744723 TI - Vignettes: personal assessments. PMID- 17744724 TI - An activist in paleontology. PMID- 17744725 TI - Products & materials. PMID- 17744726 TI - Metric system wins over british. PMID- 17744727 TI - UFO Phenomena. PMID- 17744728 TI - The university president. PMID- 17744729 TI - Reply by j. Mehler and T. G. Bever. PMID- 17744730 TI - Consulting: u.s. Firms thrive on jobs for European clients. PMID- 17744731 TI - Campaign postmortem: contrasts with 1964. PMID- 17744732 TI - Contraceptive Properties of Stevia rebaudiana. AB - A water decoction of the plant Stevia rebaudiana Bertoni reduces fertility in adult female rats of proven fertility. The decoction continues to descrease fertility for at least 50 to 60 days after intake is stopped. The decoction did not affect appetite and apparently did not affect the health of adults rats. PMID- 17744734 TI - Balloon surgery. PMID- 17744733 TI - The prehistory of the nile valley. PMID- 17744736 TI - Indirect costs. PMID- 17744735 TI - Indirect costs. PMID- 17744737 TI - Indirect costs. PMID- 17744738 TI - Genetic effects of atomic bombs. PMID- 17744740 TI - Military grapples with the chaos factor. PMID- 17744739 TI - Coral snake mimicry: does it occur? AB - Field observations and experimental evidence refute previous objections to the coral snake mimicry hypothesis. Concordant color pattern variation spanning hundreds of miles and several presumed venomous models strongly suggests that several harmless or mildly venomous colubrid snakes are indeed mimics of highly venomous elapids. PMID- 17744741 TI - Airfield alarms astronomers. PMID- 17744742 TI - A question of accuracy. PMID- 17744743 TI - Round two of budget cuts is approaching. PMID- 17744744 TI - Study shows formaldehyde is carcinogenic. PMID- 17744745 TI - Research information service imperiled. PMID- 17744746 TI - How to become an academy member. PMID- 17744747 TI - Nuclear War Worse Than Atomic Power, Say M.D.'s. PMID- 17744749 TI - New patent rule upsets universities. PMID- 17744748 TI - NSA Seeks Research Proposals. PMID- 17744751 TI - Saturn redux: the voyager 2 mission. PMID- 17744750 TI - An empty plan for renewable energy. PMID- 17744752 TI - Neptune's Rings Fading. PMID- 17744754 TI - Kin organizations. PMID- 17744753 TI - A quest for human traces. PMID- 17744755 TI - Sophisticated designs. PMID- 17744756 TI - Patterns of predation. PMID- 17744757 TI - Microbial origin of desert varnish. AB - Scanning electron microscopy and energy dispersive x-ray analyses of desert varnish reveal that microorganisms concentrate ambient manganese that becomes greatly enhanced in brown to black varnish. Specific characteristics of desert varnish and of varnish bacteria support a microbial origin for manganese-rich films. Varnish microbes can be cultured and produce laboratory manganese films. Accordingly, natural desert varnish and also manganese-rich rock varnishes in nondesert environments appear to be a product of microbial activity. PMID- 17744758 TI - Oxygen-18 enrichment of planktonic foraminifera due to gametogenic calcification below the euphotic zone. AB - Empty shells of spinose planktonic foraminifera on the seabed are significantly enriched in oxygen-18 as compared with the shells of their living counterparts in surface waters. This enrichment is due to gametogenic calcification, which extracts calcium carbonate from deeper and colder waters as the shell sinks below the euphotic zone. JEAN-CLAUDE DUPLESSY. PMID- 17744759 TI - Radar detection of cloud-seeding effects. AB - The effects on precipitation of artificially seeding clouds with Dry Ice have been monitored from cloud to ground with a radar that has a wavelength of 8.6 millimeters. PMID- 17744760 TI - Competition for dispersal in ant-dispersed plants. AB - Two closely related and coexisting plants (Chenopodiaceae) of the Australian arid zone are adapted for seed dispersal by ants. These facultatively perennial shrubs persist in saltbush communities largely as a result of highly directional dispersal to ant mounds, where conditions are favorable for establishment and growth. The two species grow predominantly on mounds and compete for dispersal to these favorable microhabitats. PMID- 17744761 TI - Selective herbivory in tassel-eared squirrels: role of monoterpenes in ponderosa pines chosen as feeding trees. AB - Ponderosa pine twigs collected from trees used by tassel-eared squirrels as sources of cortical tissue for food contained smaller amounts of monoterpenes than twigs from similar trees not used by the squirrels as food sources. Of the 18 monoterpenes isolated from the twig samples, alpha-pinene was the best single predictor of food source trees. In experiments with captive tassel-eared squirrels, consumption of a preferred food was inversely correlated with the concentration of alpha-pinene added to the food. PMID- 17744762 TI - Altruism in an antarctic fish. PMID- 17744763 TI - Altruism in an antarctic fish. PMID- 17744764 TI - PRODUCTS and MATERIALS. PMID- 17744765 TI - This week in science. PMID- 17744766 TI - Need for enhanced nuclear safeguards. PMID- 17744767 TI - Superconductor radiation damage after doping. PMID- 17744768 TI - An inclusive budget process. PMID- 17744769 TI - Response. PMID- 17744771 TI - Dispute Over Company Link Roils CEPH. PMID- 17744770 TI - Sciencescope. PMID- 17744772 TI - Genethon: an industrial approach to isolating genes. PMID- 17744774 TI - Fire ants parlay their queens into a threat to biodiversity. PMID- 17744773 TI - Professor slams mit over center closure. PMID- 17744775 TI - Did pinatubo send climate-warming gases into a dither? PMID- 17744776 TI - First satellite of an asteroid discovered. PMID- 17744777 TI - A lunar idea. PMID- 17744778 TI - Journal quails over oiled turtles. PMID- 17744779 TI - New CF Drug Goes Pro Bono. PMID- 17744781 TI - Soviet-style conundrums for u.s. Youth. PMID- 17744780 TI - U.k. Research council gets oxford head. PMID- 17744782 TI - Lefty longevity: another study. PMID- 17744783 TI - Spatiotemporal chaos. PMID- 17744784 TI - Why snakes have forked tongues. AB - The serpent's forked tongue has intrigued humankind for millennia, but its function has remained obscure. Theory, anatomy, neural circuitry, function, and behavior now support a hypothesis of the forked tongue as a chemosensory edge detector used to follow pheromone trails of prey and conspecifics. The ability to sample simultaneously two points along a chemical gradient provides the basis for instantaneous assessment of trail location. Forked tongues have evolved at least twice, possibly four times, among squamate reptiles, and at higher taxonomic levels, forked tongues are always associated with a wide searching mode of foraging. The evolutionary success of advanced snakes might be due, in part, to perfection of this mechanism and its role in reproduction. PMID- 17744785 TI - 5-coordinate si compounds as intermediates in the synthesis of silicates in nonaqueous media. AB - Sodium silicoglycolate, an organosilicon compound in which silicon is in 5 coordination with respect to oxygen, is shown to be a reaction intermediate in the synthesis of a purely siliceous sodalite with ethylene glycol as solvent. The presence of silicon-29 nuclear magnetic resonances at -105.5 +/- 0.3 parts per million in solution and -102.7 parts per million in the solid state as well as x ray powder diffraction patterns demonstrate that 5-coordinate silicon is intimately involved in the synthesis. Silicon compounds of the 5-coordinate type are highly reactive and are promising starting materials for the synthesis of novel silicone polymers, molecular sieves, glasses, semiconductors, and ceramics. We have used sodium silicoglycolate to prepare the molecular sieve silicalite as well as sodalites of different compositions. PMID- 17744786 TI - Recent changes in atmospheric carbon monoxide. AB - Measurements of carbon monoxide (CO) in air samples collected from 27 locations between 71 degrees N and 41 degrees S show that atmospheric levels of this gas have decreased worldwide over the past 2 to 5 years. During this period, CO decreased at nearly a constant rate in the high northern latitudes. In contrast, in the tropics an abrupt decrease occurred beginning at the end of 1991. In the Northern Hemisphere, CO decreased at a spatially and temporally averaged rate of 7.3 (+/-0.9) parts per billion per year (6.1 percent per year) from June 1990 to June 1993, whereas in the Southern Hemisphere, CO decreased 4.2 (+/-0.5) parts per billion per year (7.0 percent per year). This recent change is opposite a long-term trend of a 1 to 2 percent per year increase inferred from measurements made in the Northern Hemisphere during the past 30 years. PMID- 17744787 TI - Sound velocities in dense hydrogen and the interior of jupiter. AB - Sound velocities in fluid and crystalline hydrogen were measured under pressure to 24 gigapascals by Brillouin spectroscopy in the diamond anvil cell. The results provide constraints on the intermolecular interactions of dense hydrogen and are used to construct an intermolecular potential consistent with all available data. Fluid perturbation theory calculations with the potential indicate that sound velocities in hydrogen at conditions of the molecular layer of the Jovian planets are lower than previously believed. Jovian models consistent with the present results remain discrepant with recent free oscillation spectra of the planet by 15 percent. The effect of changing interior temperatures, the metallic phase transition depth, and the fraction of high atomic number material on Jovian oscillation frequencies is also investigated with the Brillouin equation of state. The present data place strong constraints on sound velocities in the Jovian molecular layer and provide an improved basis for interpreting possible Jovian oscillations. PMID- 17744788 TI - Short-lived chemical heterogeneities in the archean mantle with implications for mantle convection. AB - The neodymium isotope and samarium-neodymium systematics of 2.7-billion-year-old mantle-derived magmas indicate that the lifetime of chemical heterogeneities was much shorter in the Archean mantle than in the modern mantle. Isotopic evidence is compatible with a Rayleigh number 100 times larger and convection 10 times faster in the Late Archean compared with the present-day mantle. Modern plate tectonics thus may be an improbable analog for the Archean. Chemical heterogeneities in the mantle may originate upon magma migration and mineralogical phase changes rather than by recycling of oceanic and continental crust. PMID- 17744789 TI - Growth of diamond from atomic hydrogen and a supersonic free jet of methyl radicals. AB - The growth of small ( approximately 10-micrometer) diamond particles (on 0.1-or 0.25-micrometer seed crystals) using an effusive glow discharge nozzle for H.and a separate supersonic pyrolysis jet for .CH(3) is reported. Laser micro-Raman, scanning electron microscopy, and x-ray photoelectron spectroscopy data are presented as evidence that well-crystallized diamond is indeed formed. Resonant multiphoton ionization spectroscopy is used as a diagnostic for the gas-phase chemistry indicating that the radical sources are clean and quantitative and that there is no detectable interconversion of .CH(3) to C(2)H(2) under the conditions of the experiment. Diamond growth is found at substrate temperatures greater than or equal to 650 degrees C with no marked increase in the rate of growth up to 850 degrees C. Acetylene does not give good quality diamond under similar conditions. PMID- 17744790 TI - An in vitro system for adhesion and fusion of maize gametes. AB - The development of in vitro fertilization systems in flowering plants is important for understanding and controlling the mechanisms of fertilization. Here a method is described in which isolated maize gametes fuse. In a medium containing 5 mM calcium chloride, sperm and egg cells adhere for several minutes and then fuse within 10 seconds. The method is specific to male-female gamete pairs and results in 80 percent fusion, whereas fusions with other combinations of gametic and mesophyllic cells are less frequent. Eggs fertilized in vitro do not fuse with additional male gametes, which suggests that a block to polyspermy exists. PMID- 17744792 TI - Vignettes: discrimination. PMID- 17744791 TI - The Swedish scene. PMID- 17744793 TI - Psychology via Physiology. PMID- 17744794 TI - Living landscapes. PMID- 17744795 TI - Products & materials. PMID- 17744796 TI - THE TRANSITION FROM THE INDIVIDUAL TO THE SOCIAL LEVEL. PMID- 17744797 TI - JOHN STANLEY PLASKETT 1865-1941. PMID- 17744798 TI - THE SCHOOL OF PUBLIC HEALTH OF THE UNIVERSITY OF MICHIGAN. PMID- 17744799 TI - THE EIGHTEENTH EXPOSITION OF CHEMICAL INDUSTRIES. PMID- 17744800 TI - THE ENGINEERS' COUNCIL FOR PROFESSIONAL DEVELOPMENT. PMID- 17744801 TI - THE HAVANA CONFERENCE OF NATIONAL COMMITTEES ON INTELLECTUAL COOPERATION. PMID- 17744803 TI - AWARD OF THE PENROSE MEDAL OF THE GEOLOGICAL SOCIETY OF AMERICA. PMID- 17744802 TI - A BRITISH SOCIETY OF NUTRITION. PMID- 17744805 TI - PANTOTHEN. PMID- 17744804 TI - WAR HYSTERIA IN CANADA. PMID- 17744806 TI - DIMINUTION IN ABILITY OF THE LIVER TO INACTIVATE ESTRONE IN VITAMIN B COMPLEX DEFICIENCY. PMID- 17744807 TI - COLLECTION AND FILING OF SCIENTIFIC DATA. PMID- 17744808 TI - WANTED--SEDIMENTARY GALENAS. PMID- 17744809 TI - STUDIES ON INHIBITION OF FERMENTATION BY YEAST MACERATION JUICE. PMID- 17744810 TI - ON THE PORPHYRIN NATURE OF THE FLUORESCENT "BLOOD CAKED" WHISKERS OF PANTOTHENIC ACID DEFICIENT RATS. PMID- 17744812 TI - THE POLAROGRAPHIC CURVE OF SERUM FROM RATS FED p-DIMETHYLAMINOAZOBENZENE. PMID- 17744811 TI - VITAMIN B6 AND GROWTH OF EXCISED TOMATO ROOTS IN AGAR CULTURE. PMID- 17744813 TI - THE PREPARATION OF STERILE PROTEINS IN THE "LYOPHILED" STATE. PMID- 17744815 TI - Meetings & Conferences. PMID- 17744816 TI - Science and Human Affairs. PMID- 17744814 TI - REMOVING FROZEN PLUNGERS OF GLASS SYRINGES. PMID- 17744818 TI - Agenda for 1951. PMID- 17744819 TI - A Report of the Cleveland Meeting December 26-30, 1950. PMID- 17744817 TI - Detlev W. Bronk, Scientist. PMID- 17744821 TI - Reports of Sections and Societies. PMID- 17744820 TI - Association Business. PMID- 17744822 TI - THE ASSOCIATION OF ECONOMIC ENTOMOLOGISTS--ADDRESS BY THE PRESIDENT-- THE EVOLUTION OF ECONOMIC ENTOMOLOGY. PMID- 17744824 TI - ADDRESS BY THE VICE-PRESIDENT BEFORE SECTION I.--SOCIAL AND ECONOMIC SCIENCE.- HORTICULTURE AND HEALTH. PMID- 17744823 TI - EIGHTH ANNUAL MEETING, BUFFALO, N. Y., AUGUST 21-22, 1896. PMID- 17744825 TI - SECTION I.-SOCIAL AND ECONOMIC SCIENCE. PMID- 17744826 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17744827 TI - ON THE PENIAL STRUCTURES OF THE SAURIA. PMID- 17744828 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17744830 TI - THE GEOLOGY OF BLOCK ISLAND. PMID- 17744829 TI - ASTRONOMICAL NOTES. PMID- 17744831 TI - NEW APPLES. PMID- 17744832 TI - THE CURVE-TRACING TOP. PMID- 17744833 TI - RUTGERS COLLEGE MUSEUM. PMID- 17744835 TI - THE BOSTON MEETING. PMID- 17744834 TI - THE LIMITS OF SCIENCE. PMID- 17744836 TI - AUTUMN MEETING OF THE EXECUTIVE COMMITTEE. PMID- 17744837 TI - ANNUAL REPORT OF THE PERMANENT SECRETARY. PMID- 17744839 TI - FUNCTIONS OF THE DIVISION OF GEOLOGY AND GEOGRAPHY OF THE NATIONAL RESEARCH COUNCIL. PMID- 17744838 TI - REPORT OF THE COMMITTEE ON CONVOCATION WEEK. PMID- 17744841 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17744840 TI - NATIONAL RESEARCH COUNCIL'S MEDICAL FELLOWSHIPS. PMID- 17744842 TI - ACOUSTICAL RESEARCH. PMID- 17744844 TI - AN APPEAL. PMID- 17744843 TI - FINANCIAL SUPPORT OF TECHNICAL JOURNALS. PMID- 17744845 TI - AUSTRIAN SCIENTIFIC PUBLICATIONS. PMID- 17744846 TI - THE INTELLIGENCE OF INDIANS. PMID- 17744847 TI - ORGANIZATION OF HETEROTYPIC CHROMOSOMES. PMID- 17744848 TI - THE OPTICAL SOCIETY OF AMERICA. PMID- 17744850 TI - VENEZUELA AND COLOMBIA. PMID- 17744849 TI - THE PUMA, OR AMERICAN LION. PMID- 17744852 TI - CURRENT NOTES ON ANTHROPOLOGY. -- II. PMID- 17744851 TI - ASTRONOMICAL NOTES. PMID- 17744853 TI - The Color Question Again. PMID- 17744855 TI - The Scientific Alliance. PMID- 17744854 TI - The Question of the Celts. PMID- 17744856 TI - Professor Alexander Agassiz on the Origin of the Fauna and Flora of the Galapagos Islands. PMID- 17744857 TI - INDICATIONS AS TO CLIMATIC CHANGES FROM THE TIMBERLINE OF MOUNT WASHINGTON. PMID- 17744858 TI - "VEGETABLE DYNAMICKS" AND PLANT TISSUE CULTURES. PMID- 17744859 TI - JAMES J. WALSH. PMID- 17744860 TI - DEDICATION OF THE TECHNOLOGICAL INSTITUTE OF NORTHWESTERN UNIVERSITY. PMID- 17744861 TI - THE GEORGE F. BAKER PAVILION OF THE NEW YORK HOSPITAL. PMID- 17744862 TI - NATIONAL RESEARCH COUNCIL FELLOWSHIPS IN THE NATURAL SCIENCES. PMID- 17744863 TI - THE AMERICAN PHILOSOPHICAL SOCIETY. PMID- 17744864 TI - THE AMERICAN ACADEMY OF ARTS AND SCIENCES. PMID- 17744865 TI - GRAVEL OUTWASH NEAR CHILLICOTHE, OHIO. PMID- 17744866 TI - A CASE OF "WINE-FED" TERMITES. PMID- 17744868 TI - DISEASE IN WARTIME. PMID- 17744867 TI - AVERAGE HEIGHT OF AMERICAN MEN. PMID- 17744869 TI - SCIENTIFIC INTUITION OF A ROMAN EPICURE. A QUOTATION. PMID- 17744870 TI - THE SOUTHERN ASSOCIATION OF SCIENCE AND INDUSTRY. PMID- 17744872 TI - CONTROL OF FLOWERING WITH PHYTOHORMONES. PMID- 17744871 TI - STEROID HORMONE EXCRETION BY NORMAL AND PATHOLOGICAL INDIVIDUALS. PMID- 17744873 TI - SELF-STERILIZING SURFACES. PMID- 17744874 TI - This week in science. PMID- 17744875 TI - National institute for science and technology. PMID- 17744876 TI - Correction. AB - 29 April (p.734) and 13 May (p. 911) issues of Science The talk being given by Dr. Harold Varmus at the Science/HUGO Human Genome 1994 meeting on Monday, 3 October, in Washington, D.C., is entitled "Manipulating Cancer Genes in the Mouse." PMID- 17744877 TI - Corrections and clarifications. AB - In the Perspective "alpha-Helical coiled coils: More facts and better predictions" by C. Cohen and D. A. D. Parry (28 Jan., p. 488), the second sentence of the second paragraph of column 1 on page 489 should have read, "The structural motif is indeed a left-handed three-helix bundle with left-handed chain connectivity." PMID- 17744878 TI - Fire and ice ... And worms? PMID- 17744879 TI - Sciencescope. PMID- 17744881 TI - NSF to Emphasize Teaching In Early Career Awards. PMID- 17744880 TI - Early Retirement Program Cuts Deep Into UC Faculties. PMID- 17744882 TI - NSF Gives Urban Schools a Hand. PMID- 17744883 TI - ... Versus a lesson in biodiversity law. PMID- 17744884 TI - Ozone Has Recovered From Pinatubo's Jolt. PMID- 17744886 TI - Heavy artillery for a deer dilemma. PMID- 17744885 TI - A lesson in biodiversity economics.. PMID- 17744888 TI - DOE Lab Lives PR Nightmare. PMID- 17744887 TI - R&D Expenditures by PMA Members, 1985-94. PMID- 17744889 TI - Lithium battery takes to water--and maybe the road. PMID- 17744890 TI - Ecologist plans to let cyberlife run wild in internet reserve. PMID- 17744891 TI - Representing ocean eddies in climate models. PMID- 17744892 TI - Galileo multispectral imaging of the north polar and eastern limb regions of the moon. AB - Multispectral images obtained during the Galileo probe's second encounter with the moon reveal the compositional nature of the north polar regions and the northeastern limb. Mare deposits in these regions are found to be primarily low to medium titanium lavas and, as on the western limb, show only slight spectral heterogeneity. The northern light plains are found to have the spectral characteristics of highlands materials, show little evidence for the presence of cryptomaria, and were most likely emplaced by impact processes regardless of their age. PMID- 17744893 TI - Rechargeable lithium batteries with aqueous electrolytes. AB - Rechargeable lithium-ion batteries that use an aqueous electrolyte have been developed. Cells with LiMn(2)O(4) and VO(2)(B) as electrodes and 5 M LiNO(3) in water as the electrolyte provide a fundamentally safe and cost-effective technology that can compete with nickelcadmium and lead-acid batteries on the basis of stored energy per unit of weight. PMID- 17744894 TI - Simulating the adsorption of alkanes in zeolites. AB - The configurational-bias Monte Carlo technique is applied to simulate the adsorption of long chain alkanes in zeolites. This simulation technique is several orders of magnitude more efficient than conventional methods that can be used to simulate the adsorption of long chain alkanes. The calculated heats of adsorption are found to be in excellent agreement with experimental data. The results show a surprising chain length dependence of the heats of adsorption. This dependence has a simple molecular explanation in terms of preferential siting of the long chain alkanes. PMID- 17744895 TI - Estimates of diapycnal mixing in the abyssal ocean. AB - Profiles of diapycnal eddy diffusivity to a maximum depth of 4000 meters were derived from ocean velocity and temperature microstructure data obtained in conjunction with separate experiments in the Northeast Pacific and Northeast Atlantic oceans. These profiles indicate that in the ocean interior where the internal wave field is at background intensity, the diapycnal eddy diffusivity is small (on the order of 0.1 x 10(-4) meters squared per second) and independent of depth, in apparent contradiction with large-scale budget studies. Enhanced dissipation is observed in regions of elevated internal wave energy, particularly near steeply sloping boundaries (where the eddy diffusivity estimates exceed 1 x 10(-4) meters squared per second). These results suggest that basin-averaged mixing rates may be dominated by processes occurring near the ocean boundaries. PMID- 17744896 TI - The role of mesoscale tracer transports in the global ocean circulation. AB - Ocean models routinely used in simulations of the Earth's climate do not resolve mesoscale eddies because of the immense computational cost. A new parameterization of the effects of these eddies has been implemented in a widely used model. A comparison of its solution with that of the conventional parameterization shows significant improvements in the global temperature distribution, the poleward and surface heat fluxes, and the locations of deep water formation. PMID- 17744898 TI - Neural mechanisms. PMID- 17744897 TI - Response. PMID- 17744899 TI - A Bird's-Eye View. PMID- 17744900 TI - Early crustal evolution. PMID- 17744901 TI - Vignettes: dependencies. PMID- 17744903 TI - Products & materials. PMID- 17744902 TI - Cosmic chemistry. PMID- 17744904 TI - Erratum. AB - Important information in the article "Insulin wars: New advances may throw market into turbulence" (News and Comment, 12 Dec. 1980, p. 1225) came from a review written by Scott R. King of F. Eberstadt & Co., Inc., New York. Credit to King was inadvertently omitted from the article. PMID- 17744905 TI - Culturing before a transplant. PMID- 17744906 TI - Prepared minds. PMID- 17744908 TI - Heritage foundation: court philosophers. PMID- 17744907 TI - Theoretical organometallic chemistry. AB - Organometallic chemists have synthesized a remarkable variety of new structural types. In these structures ligands, which are organic or inorganic molecules of variable independent stability, bind to one or more transition metal atoms. An approach to an understanding of the electronic structure, geometrical preferences, and reactivity of these complexes may be made if the molecule is "decomposed" conceptually into a metal fragment, ML(n), and a ligand. A library of the molecular orbitals of these fragments is becoming available. One then "reconstructs" the molecule by examining the interaction of the orbitals of the ligand, typically an organic molecule, with the orbitals of the ML(n), fragment. PMID- 17744909 TI - Texas court rules that hughes left no will. PMID- 17744910 TI - "Flash" near South Africa, again. PMID- 17744911 TI - Teletext war comes into focus. PMID- 17744912 TI - Reagan ends mandatory conservation. PMID- 17744913 TI - Nonproliferation shuffle. PMID- 17744914 TI - Science adviser post in doubt. PMID- 17744915 TI - More shots in the budget battle. PMID- 17744916 TI - Women in science cut. PMID- 17744917 TI - Evidence for Free Quarks Won't Go Away. PMID- 17744918 TI - Looking for a needle in a haystack. PMID- 17744920 TI - New responses to attacks on human rights of scientists in latin america called for. PMID- 17744919 TI - Astronomers Look to the 1980's. PMID- 17744922 TI - Rutherford Named AAAS Adviser. PMID- 17744921 TI - R&D Project Analyzes FY 1982 Budgets. PMID- 17744923 TI - David joins board. PMID- 17744924 TI - Science ethics reprint series available. PMID- 17744925 TI - Research into Effects of a CO2-Climate Change Suggested. PMID- 17744926 TI - Special notice for advance registrants at the toronto meeting. PMID- 17744927 TI - Rotifers. PMID- 17744929 TI - Pioneer seismologist. PMID- 17744928 TI - Scientists and politicians. PMID- 17744930 TI - Psychophysiology. PMID- 17744931 TI - Turbulent Vertical Transport due to Thin Intermittent Mixing Layers in the Stratosphere and Other Stable Fluids. AB - Pollution effects in the stratosphere and the ocean are exacerbated by buoyant stability. Turbulence in such media is confined to thin layers. To estimate vertical transport by such turbulence, one can view the situation as nature's way of simulating the finite-difference diffusion equation. This analogy finally yields a diffusivity parameter which is valid for this extremely inhomogeneous case. PMID- 17744932 TI - Textural and crystal-fabric anisotropies and the flow of ice masses. AB - Accurate modeling and prediction of glacier response requires a better understanding of the influence of physical anisotropies on creep. To investigate the effects of variations in the degree of preferred crystallographic orientation and ice crystal size on creep, 19 samples of anisotropic glacier ice were deformed in simple shear. Results indicate that the time required for ice samples to reach the minimum strain rate decreases as crystal size increases; an increase in crystal-fabric development from an isotropic fabric to one with a strong single maximum results in an enhancement of the minimum strain rate by a factor of 4; and a doubling of the crystal size results in about a ninefold increase in the minimum strain rate. PMID- 17744933 TI - Anabaseine: venom alkaloid of aphaenogaster ants. AB - Anabaseine, a tobacco alkaloid, is identified as a poison gland product in Aphaenogaster ants, in which it functions as an attractant. PMID- 17744934 TI - Separation of calcium isotopes by liquid phase thermal diffusion. AB - Significant separation of the isotopes of calcium was obtained by thermogravitational thermal diffusion of an aqueous calcium nitrate solution. A flow of solvent was used to partially offset the large solute-solvent separation effect in the experimental column. Further development of this technique may lead to separation of the isotopes of calcium and of other elements on a practical scale. PMID- 17744935 TI - Sex-Biased Litter Reduction in Food-Restricted Wood Rats (Neotoma floridana). AB - Mothers of eastern wood rats (Neotoma floridana) normally invest their lactation energy equally in male and female offspring, but alter that investment when their food is severely restricted during lactation. The effect of the altered investment is a significant bias against males in both mortality and growth. PMID- 17744936 TI - THE MONTEREY PINE AND CYPRESS. PMID- 17744937 TI - A parasitic leech. PMID- 17744939 TI - Mortality experience of life-insurance companies. PMID- 17744938 TI - A novel snow-slide. PMID- 17744940 TI - A BRONZE MEDALLION PORTRAIT OF DR. ASA GRAY. PMID- 17744942 TI - THE HONG SAL MUN, OR THE RED ARROW GATE. PMID- 17744941 TI - An attempt to photograph the solar corona. PMID- 17744943 TI - THE METEOROLOGICAL OBSERVATORY ON BLUE HILL. PMID- 17744944 TI - SUNLIGHT AND THE EARTH'S ATMOSPHERE. PMID- 17744945 TI - AQUATIC PLANTS OF SAN DIEGO. PMID- 17744946 TI - Science for the Citizen. PMID- 17744947 TI - Nest Climate Regulation in Honey Bee Colonie: Honey bees control their domestic environment by methods based on their habit of clustering together. PMID- 17744948 TI - Data Processing by Optical Coincidence: This unconventional use of punched cards provides a flexible and rapid means for hand tabulation. PMID- 17744949 TI - The Test Ban: The Russians Now Say That the Inspection System Is Only "Symbolic". PMID- 17744950 TI - Occurrence of Titanium, Vanadium, Chromium, and Sulfuric Acid in the Ascidian Eudistoma ritteri. AB - The body tissues of the colonial ascidian Eudistoma ritteri are shown by quantitative spectrographic analysis to contain up to the following amounts of related metals (parts per million of dry weight): titanium, 1512; vanadium, 471; and chromium, 144. Body tissues and tunic fluid show a pH of 1.5 due to the presence of sulfuric acid. PMID- 17744951 TI - Specificity of Discrimination Learning to the Original Context. AB - Rats learned a black-white discrimination at one location in a maze. Subsequently, most rats required over half as many trials to learn the same discrimination when it was placed in another location in the maze. Additional evidence was consistent with the assumption that the relevant cues are, in effect, modified by interaction with the contextual stimuli. PMID- 17744952 TI - Auxin Gibberellic Acid Interaction in Controlling the Hypocotyl Growth in Seedlings. AB - High concentrations of indole-3-butyric acid, when applied at a concentration of 100 to 200 parts per million (ppm) to presoaked seeds, cause a marked inhibition of hypocotyl length in the seedling growth of Phaseolus mungo var. T-2. Gibberellic acid, when applied at a concentration of 5 ppm, quantitatively reversed this inhibition. It is suggested that the interaction between these two growth substances controls the morphogenetic differentiation in regard to hypocotyl formation in seedling growth. PMID- 17744953 TI - Giant Desiccation Fissures on the Black Rock and Smoke Creek Deserts, Nevada. AB - Open fissures, from 100 to several hundred feet apart, that have produced polygonal patterns on the Black Rock Desert, Nevada, are believed to be giant desiccation cracks resulting from a secular trend toward aridity in the last few decades. Similar features on the Smoke Creek Desert probably have the same origin. PMID- 17744954 TI - Reactivation of Rabies Virus Infection with Adrenocorficotropic Hormones. AB - A guinea pig inoculated intramuscularly with rabies street virus survived for 5 months, but developed paralysis in the inoculated limb and died of rabies after treatment with adrenocorticotropic hormone. PMID- 17744955 TI - An Advancing Glacier in Canada. AB - The Commander Glacier, in the Purcell Range of interior British Columbia, advanced 810 +/- 50 feet in the 6 years 1954-1960. The advance may be a response to a general cooling trend previously noted elsewhere in the Pacific Northwest. PMID- 17744956 TI - National Academy of Sciences: Abstracts of Papers Presented at the Annual Meeting, 24-26 April 1961, Washington, D.C. PMID- 17744957 TI - Forthcoming Events. PMID- 17744958 TI - Open letter. PMID- 17744960 TI - The structure of discovery. PMID- 17744959 TI - The motion of ions: principles and concepts. PMID- 17744961 TI - Soviets, west discuss "think tank". PMID- 17744962 TI - Food delegates focus on poor. PMID- 17744963 TI - Pentagon promises to observe congressional curbs on research. PMID- 17744965 TI - Mariners 6 and 7: radio occultation measurements of the atmosphere of Mars. AB - Radio occultation measurements with Mariners 6 and 7 provided refractivity data in the atmosphiere of Mars at four points above its surface. For an atmosphere consisting predominantly of carbon dioxide, surface pressures between 6 and 7 millibars are obtained at three of the points of measurement, and 3.8 at the fourth, indicating an elevation of 5 to 6 kilometers. The temperature profile measured by Mariner 6 near the equator in the daytime indicates temperatures in the stratosphere about 100 degrees K warmer than those predicted by theory. The measurements of Mariner 6 taken at 79 degrees N at the beginning of polar night indicate that conditions are favorable for the condensation of carbon dioxide at almost all altitudes. Mariner 7 measurements taken at 58 degrees S in daytime and 38 degrees N at night also show that carbon dioxide condensation is possible at altitudes above about 25 kilometers. Measurements of the electron density in the ionosphere show that the upper atmosphere is substantially warmer than it was in 1965, possibly because of increased solar activity and closer proximity to the sun. PMID- 17744966 TI - Tuhualite crystal structure. AB - As judged by crystal structure analysis, the crystallochemical formula of tuhualite is (Na,K)(2)(VI) (Fe(+3))(2)(VI) (Fe(+2))(2)(VI) Si(12)O(30) . H(2)O, with four such formulas in the unit cell. The structure is characterized by six repeat double chains of silicon tetrahedrons and chains of edge-sharing, alternating iron tetrahedrons and octahedrons. Chains of each kind are connected by corner sharing to four chains of the other type. The iron cations appear to be anomalously ordered with Fe(+2) in tetrahedral and Fe(+3) in octahedral sites. PMID- 17744967 TI - Interstellar scintillations of pulsar radiation. AB - Time fluctuations in the intensity of pulsed radiation from CP 0834, CP 1133, AP 1237, and CP 1919 have been investigated. Power spectra, modulation indices, frequency distributions, and decorrelation frequencies are consistent with scintillation theory. If it is assumed that these scintillations are due to irregularities in the interstellar medium that travel at a velocity of 20 kilometers per second, the irregularities have a scale size on the order of 10(4) kilometers and a distance from the earth of approximately 70 parsecs. These interstellar scintillations would not have been observed if the apparent angular diameters of the pulsars were larger than 0.3 X 10(-5) second of arc, and they would cause even a point radio source to have an apparent angular diameter of approximately 10(-3) second of arc at 318 megahertz. PMID- 17744968 TI - Divalent phosphate electrode. AB - Divalent phosphate ion activities can be measured in dilute aqueous solutions in the physiological pH range (7.0 to 7.5) with a liquid ionexchange membrane electrode system; the organic ion exchanger consists of an amine chloride membrane. Reference solutions may be either aqueous chloride or bicarbonate solutions. An essentially Nernstian slope is obtained. PMID- 17744969 TI - Structure of an oxygen-carrying cobalt complex. AB - Bis(3-fluorosalicylaldehyde) ethylenediimine cobalt(II), a reversible oxygen carrying compound, has been crystallized as a tetramer with two oxygen molecules bound to the four cobalt atomns, each oxygen molecule bridging between two metal atoms. These dimers are further linked by two bonds between the oxygen atom of the salicylaldehyde and the cobalt atom. The oxygen-to-oxygen distance, 1.21 angstroms in molecular oxygen, has increased to 1.308(28) angstroms (where the number in parentheses is the estimated standard deviation) in this compound, the shortest distance yet observed in sutch a bridging arrangement. PMID- 17744970 TI - Benzene Complexes with Copper(II)montmorillonite. AB - Benzene formed a stable coinplex through its pi electrons to the copper ion in copper(II)montmorillonite. Copper(II)was the only exchangeable metal cation in montmorillonite to form a complex with benzene. Only those clay minerals whose charge arises in the octahedral layer produced the complex. PMID- 17744971 TI - Pathotoxin-induced disease resistance in plants. AB - Primary leaves of bean plants treated with nonphytotoxic concentrations of the pathotoxin victorin were rendered highly resistant to two plant viruses. Leaves treated with higher concentrations of victorin became necrotic. These effects on plants that are resistant to victorin and to the fungus that produces it lend support to the hypothesis that activation of a defensive self-repair mechanism may account for resistance to this highly selective pathotoxin. PMID- 17744973 TI - Why is the moon gray? PMID- 17744972 TI - Androgenesis conditioned by a mutation in maize. AB - A maize embryo having the nuclear constitution of a reduced gametophyte cell is produced in 3 percent of the embryo sacs of inbred strain Wisconsin-23 that carry the mutant indeterminate gametophyte (ig). The nucleus of most monoploid sporophytes so derived is paternal. Such androgenetic monoploids may originate from a sperm nucleus acting in conjunction with the cytoplasm of a maternal cell from which the nucleus has been functionally displaced. PMID- 17744974 TI - Irreversible Thermodynamics and Flow across Membranes. PMID- 17744975 TI - AAAS Symposia. PMID- 17744976 TI - The sorry state of science. PMID- 17744978 TI - Forthcoming events. PMID- 17744977 TI - Science and survival: the pugwash conference at sochi, u.s.s.R. PMID- 17744979 TI - SCIENCE NEWS. PMID- 17744980 TI - THE PARASITE INDUCING PEARL FORMATION IN AMERICAN FRESHWATER UNIONIDAE. PMID- 17744981 TI - THE OLDEST KNOWN PLANT VIRUS DISEASE. PMID- 17744982 TI - THE DISGRACE OF GERMAN SCIENCE. PMID- 17744983 TI - A PECULIAR OPTICAL PHENOMENON. PMID- 17744984 TI - TOBACCO SMOKING AND BLOOD SUGAR. PMID- 17744985 TI - GRANTS OF THE AMERICAN PHILOSOPHICAL SOCIETY. PMID- 17744986 TI - A SIMPLE METHOD FOR THE ISOLATION OF GLUTATHIONE FROM YEAST. PMID- 17744987 TI - AN ADJUSTABLE STAGE FOR MICROSCOPES. PMID- 17744988 TI - METHYLENE BLUE AND GASSED PLANTS. PMID- 17744989 TI - THE PRESENCE OF PHOSPHORUS IN THE SUN. PMID- 17744990 TI - RESTING SPORANGIA OF CLADOCHYTRIUM. PMID- 17744991 TI - COMMENT AND CRITICISM. PMID- 17744992 TI - The star-nosed mole amphibious. PMID- 17744993 TI - The recognition, by marine animals, of the hour of the day. PMID- 17744994 TI - SIR WILLIAM THOMSON. PMID- 17744995 TI - THE NEW VOLCANO OF THE BERING SEA. PMID- 17744996 TI - CANAL ROUTES BETWEEN THE ATLANTIC AND THE PACIFIC. PMID- 17744997 TI - CERTAIN PRINCIPLES OF PRIMITIVE LAW. PMID- 17744998 TI - SIR WILLIAM THOMSON'S BALTIMORE LECTURES. PMID- 17744999 TI - THE LIMITATIONS OF SUBMARINE TELEGRAPHY. PMID- 17745000 TI - NORTH-AFRICAN ARCHEOLOGY. PMID- 17745002 TI - AMERICAN ORIENTAL SOCIETY. PMID- 17745001 TI - THE AMERICAN PUBLIC HEALTH ASSOCIATION. PMID- 17745003 TI - SHAFT-SINKING BY FREEZING. PMID- 17745004 TI - TAIT'S LIGHT. PMID- 17745005 TI - THE MAMMALS OF THE ADIRONDACKS. PMID- 17745007 TI - GEOLOGY OF SOUTH-EASTERN PENNSYLVANIA. PMID- 17745006 TI - THE MOSSES OF NORTH AMERICA. PMID- 17745008 TI - IS THERE LIFE ON THE OTHER WORLDS? PMID- 17745009 TI - THE MECHANISM OF SPECIES ADAPTATION TO CARCINOGENS. PMID- 17745011 TI - DRUG CONTROL IN INDIA. PMID- 17745010 TI - SIR WILLIAM BRAGG. PMID- 17745012 TI - NEW YORK CHAPTER OF THE SCIENCE SOCIETY OF CHINA. PMID- 17745013 TI - THE FLORA OF CUBA. PMID- 17745014 TI - CONSERVATION AND SOUTH AMERICAN EXPEDITIONS. PMID- 17745015 TI - MEETING OF EXPERIMENTAL BIOLOGISTS IN OREGON. PMID- 17745016 TI - THE AMERICAN COMMISSION ON SCIENTIFIC NOMENCLATURE IN ENTOMOLOGY. PMID- 17745017 TI - SOIL FERTILITY AND MANURING IN CHINA. PMID- 17745018 TI - ON THE NATURE OF VIRUS ADAPTATIONS. PMID- 17745019 TI - BLUEBERRY STORAGE. PMID- 17745020 TI - URETHANE: ABSENCE OF PARALLELISM WITH THE ANTI-SULFONAMIDE ACTION OF p AMINOBENZOIC ACID. PMID- 17745021 TI - NORTH CAROLINA ACADEMY OF SCIENCE. PMID- 17745022 TI - THE WISCONSIN ACADEMY OF SCIENCE. PMID- 17745024 TI - PHYSIOLOGIC STUDIES ON THE CORNEA. PMID- 17745023 TI - THE RELATION OF URINARY CITRIC ACID EXCRETION TO THE MENSTRUAL CYCLE AND THE STEROIDAL REPRODUCTIVE HORMONES. PMID- 17745025 TI - PHYSIOLOGICAL ACTIVITY OF ASCORBIC ACID IN PLANT LIFE. PMID- 17745026 TI - A QUANTITATIVE VAPORIZER. PMID- 17745027 TI - AN EGG INOCULATOR AND SHELL MEMBRANE TEASER FOR VIRUS CULTURE. PMID- 17745028 TI - HEAT INACTIVATION OF WHEAT MOSAIC VIRUS IN SOILS. PMID- 17745030 TI - INTERNATIONAL RELATIONS IN SCIENCE. PMID- 17745029 TI - SCIENCE NEWS. PMID- 17745031 TI - SCIENCE WEEK IN NEW YORK. PMID- 17745032 TI - WALTER LE CONTE STEVENS. PMID- 17745033 TI - THE APPEARANCE OF INSTABILITY OF CONDENSED SUBSTANCES NEAR THE ABSOLUTE ZERO OF TEMPERATURE. PMID- 17745034 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17745036 TI - CONTRIBUTIONS ASKED FOR MEMORIAL TO LAPLACE. PMID- 17745035 TI - ETHYLENE IS A RIPENER OF FRUITS AND VEGETABLES. PMID- 17745037 TI - GALILEI OR GALILEO? PMID- 17745039 TI - VITAMINS A, D AND E AND THE OXIDATION OF FATS AND OILS. PMID- 17745038 TI - BANANA STOWAWAYS. PMID- 17745041 TI - MODIFICATIONS IN CHILODON UNCINATUS PRODUCED BY ULTRAVIOLET LIGHT. PMID- 17745040 TI - THE NATIONAL ACADEMY OF SCIENCES. PMID- 17745042 TI - RESULTS VS. IDEALS IN TECHNICAL EDUCATION. PMID- 17745043 TI - INTERNATIONAL EXCHANGE OF STUDENTS. PMID- 17745044 TI - THE WINNIPEG MEETING OF THE BRITISH ASSOCIATION. PMID- 17745045 TI - THE DARWIN CENTENARY AT CAMBRIDGE. PMID- 17745046 TI - THE FUNDAMENTAL LAWS OF MATTER AND ENERGY. PMID- 17745047 TI - SOME TRENDS IN HIGHER EDUCATION. PMID- 17745048 TI - WARNING TO ZOOLOGISTS AND OTHERS. PMID- 17745050 TI - THE FUNDAMENTAL PRINCIPLES OF ALGEBRA. PMID- 17745051 TI - PROCEEDINGS OF THE BOTANICAL CLUB OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE AI COLUMBUS, AUGUST 21-24, 1899. PMID- 17745049 TI - ON THE RESTORATION OF SKELETONS OF FOSSIL VERTEBRATES. PMID- 17745052 TI - THE AMIERICAN MICROSCOPICAL SOCIETY. PMID- 17745054 TI - A CARD CENTRALBLATI OF PHYSIOLOGY. PMID- 17745053 TI - PROCEEDINGS OF THE SIXTEENTH ANNUAL CONVENTION OF THE ASSOCIATION OF OFFICIAL AGRICULTURAL CHEMISTS, HELD ATSAN FRANCISCO, JULY 5-7, 1899. PMID- 17745055 TI - THE PROPER NAME OF THE POLAR BEAR. PMID- 17745056 TI - THE MENTAL EFFECTS OF THE WEATHER. PMID- 17745057 TI - THE BACILLUS ICTEROIDES AS THE CAUSE OF YELLOW FEVER. PMID- 17745058 TI - INTERNATIONAL CONGRESS ON TUBERCULOSIS. PMID- 17745059 TI - Meetings & Conferences. PMID- 17745060 TI - Angular Correlation of Nuclear Radiations. PMID- 17745061 TI - A Discontinuous Paper Drive. PMID- 17745062 TI - RECENT ARCHEOLOGICAL RESEARCH IN LATIN AMERICA. PMID- 17745063 TI - THE PROBLEMS OF AGING AND OF VASCULAR DISEASES. AB - The increase in death rate with increasing age over that at the age of ten accounts for over a million deaths each year in the United States. To what extent these deaths are due to the aging process remains to be determined, but the progressive loss of resistance to nearly all diseases appears to play a large role even in youth and middle life. Since loss of resistance to disease, as well as loss of ability, seems to result from an underlying aging process we may look upon aging as constituting our greatest medical problem. Second in importance to the aging problem is that of the vascular and renal diseases, since these are involved in nearly 50 per cent. of the deaths after the age of ten (in addition to the effect of aging). Until more is known about aging and vascular diseases we are not justified in predicting what can or can not be done about them. A new experimental method in which healthy animals of different ages are killed by a known measurable cause offers possibilities for determining the nature of the aging process. Our two outstanding medical problems are being neglected largely because of the lack of funds to support both the long-term research and the raising of old animals needed for adequate investigation in this field. New endowments as well as changes in the policies of existing foundations are urgently needed. PMID- 17745064 TI - CHARLES WILLIAM LINES, JR. September, 1920-January, 1942. PMID- 17745065 TI - HEALTH SERVICES OF THE COMMONWEALTH FUND. PMID- 17745066 TI - NEW HAVEN INDUSTRIAL MEDICAL SERVICE. PMID- 17745068 TI - STALIN PRIZES. PMID- 17745067 TI - THE INTER-AMERICA BUREAU OF THE NEW YORK ACADEMY OF MEDICINE. PMID- 17745069 TI - THE SHORTAGE OF TECHNICALLY TRAINED CHEMISTS. PMID- 17745070 TI - A TWELVE-MONTH COLLEGE YEAR: AN ALL-OUT PROGRAM. PMID- 17745071 TI - MEAN SEA LEVEL AND SAND MOVEMENT; A REPLY. PMID- 17745072 TI - ON TOAD AND FROG ABUNDANCE AFTER HEAVY RAINFALL. PMID- 17745074 TI - FISHERIES LITERATURE FOR CHINA. PMID- 17745073 TI - ANALYSIS OF POST-WAR PROBLEMS AND PROCEDURES. PMID- 17745075 TI - CALENDAR REFORM AND THE NATIONAL ACADEMY OF SCIENCES. PMID- 17745076 TI - THE JAMES RIVER DRAINAGE AREA. PMID- 17745077 TI - DEFENSE WORK OF THE CARNEGIE INSTITUTION OF WASHINGTON. PMID- 17745078 TI - A BASIC MECHANISM IN THE BIOLOGICAL EFFECTS OF TEMPERATURE, PRESSURE AND NARCOTICS. PMID- 17745081 TI - FERTILE TETRAPLOIDS OF SESAME, SESAMUM INDICUM LOEW, INDUCED BY COLCHICINE. PMID- 17745080 TI - A MODEL GEYSER. PMID- 17745079 TI - SUCCESSFUL REARING OF A SECOND GENERATION OF MICE ON AN ARTIFICIAL DIET. PMID- 17745083 TI - Sociobiology: the underlying concept. PMID- 17745082 TI - ORIGIN OF DIPEPTIDASE IN A PROTOZOAN. PMID- 17745084 TI - Neuroendocrinology: pioneering efforts. PMID- 17745085 TI - The icarus legend. PMID- 17745086 TI - Unidentified abbreviations. PMID- 17745087 TI - Obsolete instrumentation at universities. PMID- 17745088 TI - River quality assessment implications of a prototype project. AB - The U.S. Geological Survey recently completed an intensive river quality assessment study of the Willamette River basin, Oregon. The most noteworthy finding was that across-the-board advanced waste treatment was not the answer to the problem of meeting stringent water quality standards established for the Willamette River. This implies that rigid nationwide standards and regulations are likely to result in unneeded expenditures in some river basins and in unachieved standards in others. It was also found that existing water quality data collected under monitoring- and surveillance-type programs are inadequate for defining the critical cause-effect relationships that control river quality problems. Intensive, synoptic surveys keyed to local problems and conditions are required to provide an adequate information base for making key management decisions. PMID- 17745089 TI - Political Fracas over Peer Review Is Factor in Firing of NIAAA Director. PMID- 17745091 TI - House fiddles with the budget while interest groups burn. PMID- 17745090 TI - NASA Seeing Stars, but Not from Space Telescope. PMID- 17745092 TI - Health institutes get major boost. PMID- 17745093 TI - Quantity a key to military strength. PMID- 17745094 TI - Nuclear wastes: the science of geologic disposal seen as weak. PMID- 17745095 TI - Congressional Committees Ponder Whether to Give States a Right of Veto over Radioactive Waste Repositories. PMID- 17745096 TI - Sea water and the Ocean Crust: The Hot and Cold of It. PMID- 17745097 TI - Killer bees: o death, where is thy sting? PMID- 17745098 TI - Transient events in space. PMID- 17745099 TI - Law and psychology. PMID- 17745100 TI - Researchers on radioactivity. PMID- 17745101 TI - Carbonate deposition. PMID- 17745102 TI - Diamonds. PMID- 17745103 TI - High-pressure physics: sustained static generation of 1.36 to 1.72 megabars. AB - The pressure in experiments with the diamond-window pressure cell exceeded 1.7 megabars (at 25 degrees C). This is the highest sustained pressure ever generated under static conditions where the pressure in the sample itself was measured. At 1.72 megabars, macroscopic flow of one of the diamond pressure faces was observed. PMID- 17745104 TI - Chytrid-like fossils of pennsylvanian age. AB - Chytrid-like fungal sporangia are described occurring in saccate pollen grains of Pennsylvanian age. Both endo- and epibiotic sporangia are present, and may exhibit discharge papillae and a coarse rhizomycelium. Sporangial features, choice of substrate, and the presence of a light refractile body in presumed zoospores suggest relationships with the Chytridiales. PMID- 17745105 TI - Visualization and Transport of Positron Emission from Proton Activation in vivo. AB - Heavy charged particle beams can be widely used for cancer therapy if control in heterogeneous tissue is proved practical. A beam of protons at 200 million electron volts has been visualized in plastic and in a living animal by using an on-line positron camera. The fraction of the activity retained in the radiation site was found to be at least 70 percent of that produced in a dead animal. The sensitivity of the technique was established for a typical geometry. PMID- 17745106 TI - Absence of microorganisms in crustacean digestive tracts. AB - Two marine and one terrestrial wood-boring isopod species and one wood-inhabiting amphipod species maintain a digestive tract free of microorganisms. Digestive tracts examined in toto with the scanning electron microscope were devoid of microorganisms. In contrast, the outer exoskeleton surfaces of these crustaceans support a dense bacterialflora. Observations of the hindgut of termites revealed a diverse gut microflora as expected. PMID- 17745107 TI - Disturbance and the dispersal of fleshy fruits. AB - Fruits of Prunus serotina, Phytolacca americana, and Vitis vulpina were placed during separate trials in forest sites that varied in the degree to which the forest canopy was disturbed. Removal rates of fruits were consistently faster in the forest edge and light gap sites than in sites under closed canopy. Rapid removal of fruits from species that ripen fruit in summer and early fall is selectively advantageous to the plants because it minimizes the probability that fruits will be destroyed by invertebrates before dispersal. Disturbances probably play an important role in interactions between temperate fruits and birds and in community organization. PMID- 17745108 TI - Calcareous deposits in the renal sac of a molgulid tunicate. AB - Weddellite (calcium oxalate dihydrate) and calcite (anhydrous calcium carbonate phase) are components of concretions in the renal sac of the ascidian tunicate Molgula manhattensis. The presence of weddellite along with urate in the concretions suggests a resemblance to human kidney stones, although, unlike the latter, the concretions in Molgula do not seem to be pathologic deposits. PMID- 17745109 TI - Sexual Parasitism in the Green Tree Frog (Hyla cinerea). AB - Noncalling adult male tree frogs were found in close association with about 16 percent of the calling males in a pond in Georgia. In 13 of 30 field experiments a noncalling satellite male intercepted and achieved amplexus with a gravid female moving toward the calling male. This mating strategy, which conserves energy required for calling, resembles the strategy employed by other vertebrates. PMID- 17745110 TI - Do albumin clocks run on time? PMID- 17745111 TI - Autonomous timer in malpighian tubules. PMID- 17745112 TI - Electropositive potential measured in plant protoplast. PMID- 17745113 TI - Autonomous timer in malpighian tubules. PMID- 17745114 TI - PRODUCTS and MATERIALS. PMID- 17745115 TI - THE NEW FRONTIERS IN THE ATOM. PMID- 17745116 TI - HOWARD WALTON CLARK. PMID- 17745118 TI - THE ROYAL OBSERVATORY, GREENWICH. PMID- 17745117 TI - COSMIC RAY INVESTIGATIONS. PMID- 17745119 TI - COMMISSION TO CHINA ON MALARIA CONTROL. PMID- 17745120 TI - SYMPOSIA AT THE ATLANTIC CITY MEETING OF THE AMERICAN CHEMICAL SOCIETY. PMID- 17745121 TI - THE FIFTIETH ANNIVERSARY OF THE UNIVERSITY OF CHICAGO. PMID- 17745122 TI - THE MAGNETIC CURRENT. PMID- 17745123 TI - EFFECT OF THYMUS EXTRACT INJECTIONS ON RATS. PMID- 17745124 TI - HOW MANY SPECIES OF PLANTS ARE THERE? PMID- 17745126 TI - THE GIANT CYCLOTRON. PMID- 17745125 TI - A NUCLEUS-LIKE STRUCTURE IN A STAPHYLOCOCCUS. PMID- 17745127 TI - FAILURE OF BARLEY TO FIX MOLECULAR N15. PMID- 17745128 TI - CROWN GALL PRODUCTION BY BACTERIA-FREE TUMOR TISSUES. PMID- 17745129 TI - COLLODION FIXATION: A NEW IMMUNOLOGICAL REACTION. AB - Collodion fixation by immunological complexes presents a method of great delicacy about 1,000 times that of any heretofore described reaction. This delicacy is of an order which may permit the in vitro identification of filterable viruses. PMID- 17745130 TI - INFANTILE PARALYSIS. PMID- 17745131 TI - PRESIDENT HOOVER'S CRIME INQUIRY. PMID- 17745132 TI - THE NATIONAL HEALTH INSTITUTE. PMID- 17745133 TI - YELLOW FEVER VIRUS. PMID- 17745134 TI - CLEFT PALATE. PMID- 17745135 TI - CANARY BIRDS AND MALARIA. PMID- 17745136 TI - MICE AS DISEASE CARRIERS. PMID- 17745137 TI - THE SCIENTIFIC RETROSPECT. PMID- 17745139 TI - ALFRED MAURICE WAKEMAN. PMID- 17745138 TI - RESEARCH STANDARDS IN ANIMAL HUSBANDRY. PMID- 17745140 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17745141 TI - THE SPECTRUM OF THE AURORA BOREALIS. PMID- 17745142 TI - SOUNDS REPORTED ACCOMPANYING THE FALL OF A METEOR. PMID- 17745143 TI - OBSERVATIONS OF GREEN FLASH. PMID- 17745144 TI - WINTER ACTIVITY OF THE ROOTS OF PERENNIAL WEEDS. PMID- 17745145 TI - AN ARTIST LOOKS AT GORDONIA. PMID- 17745146 TI - THE STUDY OF GEOLOGY BY AEROPLANE. PMID- 17745147 TI - AN ANTI-VIVISECTION SCREED. PMID- 17745148 TI - ANTI-EVOLUTION IN NEW ENGLAND. PMID- 17745149 TI - AMERICAN ASSOCIATION OF PHYSICAL ANTHROPOLOGISTS. PMID- 17745151 TI - THE NATIONAL OBSERVATORY QUESTION IN ITS LATEST PHASE. PMID- 17745150 TI - CIRCUIT TRANSMISSION AND INTERFERENCE OF ACTIVATION WAVES IN LIVING TISSUES AND IN PASSIVE IRON. PMID- 17745152 TI - AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. SECTION C, CHEMISTRY. PMID- 17745153 TI - MEMBERSHIP OF THE ASSOCIATION. PMID- 17745154 TI - THE BOTANICAL SOCIETY OF AMERICA. PMID- 17745156 TI - BLUE FOXES ON THE PRIBYLOF ISLANDS. PMID- 17745155 TI - THE INTERNATIONAL AERONAUTICAL CONGRESS. PMID- 17745158 TI - NATURE OF THE SPECIFIC BACTERIAL TOXINS. PMID- 17745157 TI - TYPES VERSUS RESIDUES. PMID- 17745159 TI - A BACTERIAL SOFT ROT OF CERTAIN CRUCIFEROUS PLANTS AND AMORPHOPHALLUS SIMLENSE. PMID- 17745161 TI - THE MARINE BIOLOGICAL LABORATORY AND THE CARNEGIE INSTITUTION. PMID- 17745160 TI - NOTE ON THE MULTIPLE IMAGES FORMED BY TWO PLANE INCLINED MIRRORS. PMID- 17745162 TI - THE PLANET EROS. PMID- 17745163 TI - WHAT IS THE MATTER WITH PHYSICS TEACHING? PMID- 17745164 TI - REQUIREMENTS OF A MONOGRAPH ON THE CHEMISTRY OF CELLULOSE. PMID- 17745165 TI - EUGENICS--THE AMERICAN AND NORWEGIAN PROGRAMS. PMID- 17745166 TI - SAMUEL STOCKTON VOORHEES. PMID- 17745167 TI - LATITUDE AND VERTEBRAe. PMID- 17745168 TI - ABSTRACTS AND TITLES OF SCIENTIFIC ARTICLES FROM THE LIBRARIAN'S STANDPOINT. PMID- 17745169 TI - LONGITUDINAL ELECTROMAGNETIC FORCES. PMID- 17745170 TI - THE SCIENTIFIC BUREAUS OF THE GOVERNMENT. PMID- 17745171 TI - A PRECISION DETERMINATION OF THE DIMENSIONS OF THE UNIT CRYSTAL OF ROCK SALT. PMID- 17745172 TI - THE AMERICAN ELECTROCHEMICAL SOCIETY. PMID- 17745173 TI - THE OPTICAL SOCIETY OF AMERICA. PMID- 17745174 TI - This Week in SCIENCE. PMID- 17745175 TI - French educational reform. PMID- 17745176 TI - Sciencescope. PMID- 17745178 TI - GONG Gets Going. PMID- 17745177 TI - A ;;Bridge-to-Transplant''. PMID- 17745179 TI - Canadian federal lab goes private. PMID- 17745180 TI - Oceanography on ice. PMID- 17745181 TI - A job well done at pinatubo volcano. PMID- 17745182 TI - Hand ax throws light on European prehistory. PMID- 17745183 TI - The economics of pesticide use and regulation. AB - Pesticides enhance agricultural productivity, but the environmental and health side effects of their use justify government regulation, a subject of continuing societal debate. Bans on pesticide use are the principal regulatory device used in the United States. The economic impacts of such bans depend on the availability of substitutes, supply and trade conditions, and research and development. Without substitutes, pesticide bans result in reduced production levels and higher prices, a substantial loss of discretionary income to consumers, and a redistribution of income among agricultural producers. Most food safety concerns can be addressed by establishing standards and markets for pesticide-differentiated products, but worker safety and clean water concerns will require direct controls. Pesticide-use fees are shown to be more efficient than outright pesticide bans as a mechanism to obtain environmental goals. PMID- 17745184 TI - Numerical models of extragalactic radio sources. AB - Numerical simulations with supercomputers allow analysis of the wide range of nonlinear physics inherent in the hydrodynamic and magnetohydrodynamic equations. When applied to extragalactic radio sources, these numerical models have begun to reproduce many of the complex structures observed on telescopic images. This combination of telescopic and numerical observations provides powerful probes of the physics of radio galaxies. In this review, some of the recent results from both two-dimensional and three-dimensional numerical simulations of the formation and evolution of extended radio morphologies are described. These numerical models have allowed the exploration of important physical phenomena including the role of magnetic fields in the dynamics and emissivity of extended radio galaxies, intermittent outflow from the cores of active galaxies, instabilities and disruption of fluid jets, and the bending of collimated outflows by motion through the intergalactic medium. PMID- 17745185 TI - Occurrence of Earth-like bodies in planetary systems. AB - Present theories of terrestrial planet formation predict the rapid ;;runaway formation'' of planetary embryos. The sizes of the embryos increase with heliocentric distance. These embryos then merge to form planets. In earlier Monte Carlo simulations of the merger of these embryos it was assumed that embryos did not form in the asteroid belt, but this assumption may not be valid. Simulations in which runaways were allowed to form in the asteroid belt show that, although the initial distributions of mass, energy, and angular momentum are different from those observed today, during the growth of the planets these distributions spontaneously evolve toward those observed, simply as a result of known solar system processes. Even when a large planet analogous to ;;Jupiter'' does not form, an Earth-sized planet is almost always found near Earth's heliocentric distance. These results suggest that occurrence of Earth-like planets may be a common feature of planetary systems. PMID- 17745186 TI - Heat conductivity of amorphous solids: simulation results on model structures. AB - Through numerical simulation and consideration of phonon scattering by two-level states, the heat conductivity kappa(T), where T is temperature, has been calculated on model structures. The values obtained are in good quantitative agreement with measured data on polymethylmethacrylate, epoxy, amorphous selenium, and amorphous silicon dioxide over the temperature range 0.1 to 100 K. The calculated results reproduce the plateau feature, in the range of 5 to 20 K, that is generic to the heat conductivity of amorphous solids. Two model parameters, one characterizing the degree of structural disorder and the other related to the relaxational absorption of two-level states, are identified as being responsible for the behavior of kappa(T) at T >/= 5 K. The simulation results indicate the existence of a frequency-independent phonon diffusion regime that is consistent with the minimum phonon mean-free-path hypothesis. The magnitude of the phonon diffusion constant in this regime is shown to give a reasonable quantitative account of high-temperature kappa(T) in amorphous systems. PMID- 17745187 TI - Quantification of primary versus secondary C-h bond cleavage in alkane activation: propane on pt. AB - The trapping-mediated dissociative chemisorption of three isotopes of propane (C(3)H(8), CH(3),CD(2)CH(3), and C(3)D(8)) has been investigated on the Pt(110) (1 x 2) surface, and both the apparent activation energies and the preexponential factors of the surface reaction rate coefficients have been measured. In addition, the probabilities of primary and secondary C-H bond cleavage for alkane activation on a surface were evaluated. The activation energy for primary C-H bond cleavage was 425 calories per mole greater than that of secondary C-H bond cleavage, and the two true activation energies that embody the single measured activation energy were determined for each of the three isotopes. Secondary C-H bond cleavage is also preferred on entropic grounds, and the magnitude of the effect was quantified. PMID- 17745188 TI - Predictable upwelling and the shoreward transport of planktonic larvae by internal tidal bores. AB - Internal tidal bores have a crucial role in the transport of drifting larvae to marine nearshore populations, a key factor in structuring benthic communities. Shoreward transport of larvae and abrupt surface temperature drops lasting days can be explained by invoking the advection of subsurface cold water to the shore by internal tidal bores. This process is predictable within the lunar cycle and brings deep water to the surface (upwelling) in a direction perpendicular to the coastline. PMID- 17745189 TI - Visual systems. PMID- 17745190 TI - Molecules and the mind. PMID- 17745191 TI - Special kinds of knowledge. PMID- 17745193 TI - Products & materials. PMID- 17745192 TI - Some other books of interest. PMID- 17745195 TI - THE PHYLETIC IDEA IN TAXONOMY. PMID- 17745194 TI - THE PROBLEM OF SEVERAL BODIES: RECENT PROGRESS IN ITS SOLUTION. PMID- 17745196 TI - THE DARWIN CENTENARY AT CAMBRIDGE. PMID- 17745198 TI - A DISCLAIMER. PMID- 17745197 TI - WOLCOTT GIBBS. PMID- 17745199 TI - THE LATE PROFESSOR PACKARD'S "GUIDE TO THE STUDY OF INSECTS". PMID- 17745201 TI - THE SIXTIETH MEETING OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE, BALTIMORE, MD., DECEMBER 28-JANUARY 1, 1908-9. PMID- 17745200 TI - THE TEXAS TERTIARIES--A CORRECTION. PMID- 17745202 TI - THE AMERICAN MATHEMATICAL SOCIETY. PMID- 17745203 TI - This week in science. PMID- 17745204 TI - Product liability in a litigious society. PMID- 17745205 TI - Genesis 1:28. PMID- 17745206 TI - Response: cystic fibrosis research. PMID- 17745207 TI - SSC Takes Another Step Forward. PMID- 17745208 TI - SDI Deployment Plan Up in the Air: The program is being brought more firmly under usual channels of control in the Pentagon, deployment options are being rethought, and Congress is moving to shape the effort. PMID- 17745210 TI - A heretic amid economic orthodoxy. PMID- 17745209 TI - The Greening of the World Bank: New attention to environmental aspects of bank projects is reflected in big increase in staff, changes in economic evaluations. PMID- 17745211 TI - Antarctica Pact Could Open Way for Mining: Thirty-three nations sign a convention, overcoming differences on environmental protection, territorial sovereignty. PMID- 17745212 TI - New Superconductors Come Through: High-temperature superconductors have proved difficult to put to practical use, but recent advances in thallium-and bismuth based materials should bring applications closer to reality. PMID- 17745213 TI - Copperless superconductivity. PMID- 17745214 TI - A landmark in speech recognition. PMID- 17745215 TI - The stamp of history and ecology in amazonia. PMID- 17745216 TI - Lady bugs squash killer cockroaches. PMID- 17745217 TI - Go west, young profs. PMID- 17745219 TI - Engineers choice. PMID- 17745218 TI - The laser turns 30. PMID- 17745220 TI - Superconducting bi-ca-sr-cu-o fibers grown by the laser-heated pedestal growth method. AB - Superconducting fibers of several compositions including the nominal composition Bi(2)CaSrCu(2)O(8) have been grown by means of the laser-heated pedestal growth method. The influence of starting composition and growth conditions on structure and superconducting properties is discussed. The a-b planes of the material are parallel to the fiber axis (along the growth direction), providing the ideal condition for conduction along the copper-oxygen planes. PMID- 17745221 TI - Low lake stands in lakes Malawi and tanganyika, East Africa, delineated with multifold seismic data. AB - Seismic data reveal that water level in Lake Malawi, East Africa, was 250 to 500 meters lower before about 25,000 years ago. Water levels in Lake Tanganyika at that time were more than 600 meters below the current lake level. A drier climate appears to have caused these low stands, but tectonic tilting may also have been a contributing factor in Lake Malawi. High-angle discordances associated with shallow sequence boundaries suggest that these low stands probably lasted many tens of thousands of years. Because of its basement topography, the Lake Tanganyika basin had three separate paleolakes, whereas the Lake Malawi basin had only one. The different geographies of these paleolakes may be responsible in part for the differences in the endemic fish populations in these lakes. PMID- 17745222 TI - Response: PCB Dechlorination in Hudson River Sediment. PMID- 17745223 TI - Student cultures: campus life. PMID- 17745224 TI - Tried and True Prokaryotes: Escherichia coli and Salmonella typhimurium. PMID- 17745225 TI - Endocrine systems: endocrinology of selected invertebrate types. PMID- 17745226 TI - Products & materials. PMID- 17745227 TI - THE RELATION OF MATHEMATICS TO ENGINEERING. PMID- 17745228 TI - THE AMERICAN PHYSICAL SOCIETY. PMID- 17745229 TI - CONVOCATION WEEK. PMID- 17745230 TI - REPLY TO AN ADDRESS: PRESENT STATUS OF SOIL INVESTIGATION. PMID- 17745231 TI - WOODCOCK SURGERY. PMID- 17745232 TI - RHYTHMS OF CO2 PRODUCTION DURING CLEAVAGE. PMID- 17745233 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17745234 TI - THE ANNUAL REPORT OF THE DIRECTOR OP THE GEOLOGICAL SURVEY. PMID- 17745236 TI - EMIL ALEXANDER DE SCHWEINITZ. PMID- 17745235 TI - ELIZABETH THOMPSON SCIENCE FUND. PMID- 17745237 TI - THE MECHANICAL, THE HISTORICAL AND THE STATISTICAL. PMID- 17745238 TI - THE NATIONAL ACADEMY OF SCIENCES. PMID- 17745239 TI - THE AMERICAN PHYSICAL SOCIETY. PMID- 17745241 TI - THE AMERICAN JOURNAL OF BOTANY. PMID- 17745240 TI - THE CANADIAN ENTOMOLOGICAL SERVICE. PMID- 17745242 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17745243 TI - MINERAL NOMENCLATURE. PMID- 17745244 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17745245 TI - THE WELLESLEY FIRE. PMID- 17745246 TI - THE "GOLDEN MEAN" IN THE INHERITANCE OF SIZE. PMID- 17745247 TI - "THE LOWEST TEMPERATURE OBTAINABLE WITH ICE AND SALT". PMID- 17745248 TI - THE AMERICAN PETROLEUM SOCIETY. PMID- 17745249 TI - THE AMERICAN BISON SOCIETY. PMID- 17745250 TI - What happened at chernobyl? PMID- 17745251 TI - What happened at chernobyl? PMID- 17745252 TI - Misconduct: judgment called for. PMID- 17745253 TI - Response: misconduct: judgment called for. PMID- 17745255 TI - Gifted public servants. PMID- 17745254 TI - Gifted public servants. PMID- 17745256 TI - Biosystematics database. PMID- 17745257 TI - Rules of the game? PMID- 17745258 TI - POLITICAL GEOGRAPHY OF CENTRAL AFRICA. PMID- 17745259 TI - PHYSICAL GEOGRAPHY OF CENTRAL AFRICA. PMID- 17745260 TI - THE VEGETATION OF CENTRAL AFRICA. PMID- 17745261 TI - THE PEOPLE OF CENTRAL AFRICA. PMID- 17745262 TI - X-ray Crystallography Techniques. PMID- 17745264 TI - Ethiopian revolution. PMID- 17745263 TI - Ilya Glezer's Struggle. PMID- 17745265 TI - Standardized references. PMID- 17745266 TI - Cultural homology. PMID- 17745267 TI - Letters to the editor. PMID- 17745268 TI - Letters to the editor. PMID- 17745269 TI - Politics and unesco. PMID- 17745270 TI - Culture grammars. PMID- 17745271 TI - A historical approach to future economic growth. PMID- 17745273 TI - Strategic Weapons: Verification Keeps Ahead of Arms Control strategic arms escalator. PMID- 17745272 TI - Photocopying: high court tie vote leaves issue to congress. PMID- 17745274 TI - $8.8 Million Sought for Binary CW Production. PMID- 17745275 TI - Science adviser may return to white house. PMID- 17745276 TI - Harvard, mit face limits to growth. PMID- 17745277 TI - Human evolution: life-styles and lineages of early hominids. PMID- 17745278 TI - Sports: introducing the "happy non hooker". PMID- 17745279 TI - Pterosaur from the latest cretaceous of west Texas: discovery of the largest flying creature. AB - Three partial skeletons of a large pterosaur have been found in the latest Cretaceous nonmarine rock of West Texas. This flying reptile had thin, elongate, perhaps toothless jaws and a long neck similar to Pterodaustro and Pterodactylus. With an estimated wingspan of 15.5 meters, it is undoutbtedly the largest flying creature presently known. PMID- 17745280 TI - Gordon research conferences. PMID- 17745282 TI - VITAMINS IN THE FUTURE. PMID- 17745281 TI - PRODUCTS and MATERIALS. PMID- 17745283 TI - VITAMINS IN THE FUTURE. PMID- 17745285 TI - REMEMBERING WILLIAM JAMES. PMID- 17745284 TI - JACOB ELLSWORTH REIGHARD. PMID- 17745286 TI - A NEW BOTANICAL HALL AT CARNEGIE MUSEUM. PMID- 17745287 TI - PHYSICIANS FOR THE GOVERNMENT SERVICES. PMID- 17745288 TI - THE NATIONAL RESEARCH COUNCIL'S COMMITTEE ON THE APPLICATIONS OF THE ELECTRON MICROSCOPE. PMID- 17745289 TI - THE HALL OF NORTH AMERICAN MAMMALS OF THE AMERICAN MUSEUM OF NATURAL HISTORY. PMID- 17745290 TI - THE SOUTHWESTERN DIVISION. PMID- 17745292 TI - MEETING OF THE EXECUTIVE COMMITTEE OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17745291 TI - THE UTAH CHAPTER OF THE SOCIETY OF SIGMA XI. PMID- 17745293 TI - A GROUP THEORY DILEMMA OF SOPHUS LIE AND FELIX KLEIN. PMID- 17745294 TI - DEGREES AT ANY TIME: BRAIN CONSERVATION. PMID- 17745295 TI - PENTHESTES AND CALOPHYA. PMID- 17745297 TI - OBSERVATIONS ON AN EPIDEMIC OF POLIOMYELITIS. PMID- 17745296 TI - THE A.A.A.S. BULLETIN. PMID- 17745298 TI - THE INTRAVENOUS DRIP AND OTHER INTENSIVE METHODS FOR THE TREATMENT OF EARLY SYPHILIS. PMID- 17745299 TI - STORAGE OF RADIOACTIVE IODINE IN A METASTASIS FROM THYROID CARCINOMA. PMID- 17745300 TI - A SENSITIVE CHECK VALVE. PMID- 17745301 TI - Risk and Benefit. PMID- 17745302 TI - The Mossbauer Radiation. PMID- 17745303 TI - Donald J. Hughes, Nuclear Physicist. PMID- 17745304 TI - Oceanographic Research: Organizing Support for a Fragmented Program. PMID- 17745305 TI - Test Ban Talks: They Are Continuing Despite Summit Collapse. PMID- 17745306 TI - Atoms for Peace Awards Presented. PMID- 17745307 TI - Fourth Berkeley Symposium on Mathematical Statistics and Probability Announced. PMID- 17745308 TI - Nubian Archeological Expeditions. PMID- 17745309 TI - Biological Sciences Curriculum Study To Test New Courses. PMID- 17745310 TI - Density of the Lunar Atmosphere. AB - The minimum possible density of the lunar atmosphere at the surface is shown to be essentially the value for the interplanetary medium. This value, when combined with the observed maximum, places the particle density between 10(3) and 10(6) per cubic centimeter, while the electron density must be about 10(3) to 10(4) per cubic centimeter. These results are markedly different from those recently obtained by Firsoff. PMID- 17745311 TI - Late Glacial and Postglacial Hudson Bay Sea Episode. AB - Geological investigations, archeological studies, and radiocarbon dates indicate a similarity of events around Hudson Bay, commencing at the time Hudson Bay Basin was freed of glacier ice. The sea that then spread around Hudson Bay 7000 to 8000 years ago is here named "Tyrrell Sea." The subsequent rate of land emergence decreased exponentially. PMID- 17745312 TI - Colloidal Silica as a Standard for Measuring Absolute Fluorescence Yield. AB - The use of colloidal silica as a standard for fluorescence efficiency measurements is proposed. Its advantages over glycogen as a standard are availability, purity, and stability. Absolute fluorescence yields are reported for a number of stubstiances and compared with values in the literatUre. PMID- 17745313 TI - Negative Afterimage without Prior Positive Image. AB - A procedure is described which causes an observer to see a negative afterimage of a visual field without seeing the field itself. This phenomenon is shown to be closely related to ordinary afterimages and to temporal visual masking. PMID- 17745314 TI - A Simple Inexpensive Potometer. AB - A simple, inexpensive potometer, suitable for student use, is described. It differs from the conventional type mainly in that it does not contain a funnel and stopcock arrangement. PMID- 17745315 TI - Effect of DDT on Free Amino Acids of Susceptible and DDT-Resistant Aedes aegypti Larvae. AB - The exposure of mosquito larvae (Aedes aegypti L.) to LC(50) concentrations of DDT for various periods of time resulted in a selective increase in the alanine level of a DDT-resistant strain after 4 to 8 hours' contact with the insecticide, whereas the concentration of this amino acid in a susceptible strain remained comparatively low. PMID- 17745316 TI - Preliminary Announcement of the New York Meeting and Call for Papers by AAAS Sections. PMID- 17745318 TI - We Are for Extensive Contacts between Scientists. PMID- 17745317 TI - Forthcoming Events. PMID- 17745319 TI - Aslib. PMID- 17745321 TI - Cast of Thousands. PMID- 17745320 TI - Assay of beta-Glucuronidase. PMID- 17745322 TI - How Does a Raindrop Grow?: Precipitation in natural clouds may develop from ice crystals or from large hygroscopic aerosols. AB - On the basis of presently available data, combined with present-day knowledge of the physics and chemistry of cloud particle development, it is possible to make the following generalizations about the mode of precipitation in natural clouds. 1) The all-water mechanism begins to operate as soon as a parcel of cloud air is formed and continues to operate throughout the life of the cloud. The ice-crystal mechanism, on the other hand, can begin to operate only after the top of the cloud has reached levels where ice nuclei can be effective (about -15 degrees C). Some clouds never reach this height; any precipitation from them must be through the all-water mechanism. In cold climates and at high levels in the atmosphere, the cloud bases may be very close to this critical temperature. In the tropics, approximately 25,000 feet separate the bases of low clouds from the natural ice level. 2) The number of large hygroscopic nuclei in maritime air over tropical oceans is entirely adequate to rain-out any cloud with a base below about 10,000 feet, provided the cloud duration and cloud depth is sufficient for the precipitation process to operate. Extensive trajectories over land will decrease the number of sea-salt particles, both because of sedimentation and removal in rain. Measurements show an order-of-magnitude decrease in the number of large particles as maritime air moves from the Gulf of Mexico to the vicinity of St. Louis, during the summer months. Measurements in Arizona and New Mexico show even smaller chloride concentrations, presumably because of the long overland trajectories required in reaching these areas. The maritime particles lost in overland trajectories apparently are more than replaced by particles of land origin. The latter are usually of mixed composition and are less favorable for the formation of outsized solution droplets. 3) Ice nuclei, required for the formation of ice crystals and for droplet freezing, are rather rare at temperatures higher than about -10 degrees C. This, of course, accounts for the fact that natural clouds undergo extensive undercooling. Because of the scarcity of suitable nuclei, precipitation through the ice phase usually is not found in clouds warmer than about -15 degrees to -20 degrees C. Natural cirrus clouds might provide ice nuclei for precipitation at somewhat higher temperatures, but this possibility has not been extensively studied. 4) Precipitation in tropical clouds invariably first develops through the all-water mechanism; points discussed in paragraphs 1, 2, and 3 above all work toward this end. Tropical clouds which reach to heights above about 25,000 feet also develop precipitation through snow pellets. The data for mid-latitude clouds are conflicting. Some measurements suggest that summer clouds in the central United States and in the semiarid Southwest develop rain largely through the all-water process; existing theories support such a suggestion. However, flight measurements indicate that there is considerably more ice and snow in the clouds than can be accounted for by present theory; as a consequence, one must be careful in ruling out the ice mechanism in these areas. It appears to me, however, that the ice particles in these clouds are best accounted for through the hypothesis of freezing of drops which have grown to fairly large size through diffusion of vapor. Thus, the ice would be only incidental to the precipitation development. Winter clouds in the central United States and almost all of the clouds of northern United States and Canada appear to precipitate largely through the ice-crystal mechanism. The relatively cold cloud bases and the continental sources of air masses in these regions appear to retard the warm-rain mechanism to the point where the ice mechanism dominates. But here again, a great deal of research must be completed before a firm conclusion can be drawn (18). PMID- 17745323 TI - Science and Public Policy: Recent actions by the Federal Government in helping science and technology help the nation are surveyed. PMID- 17745324 TI - News of Science. PMID- 17745325 TI - Condylostoma--an Enemy of Bivalve Larvae. AB - In laboratory cultures, where larvae of such bivalves as oysters and clams were kept together with large ciliates of the family Condylostomidae, the latter were seen ingesting the larvae. A single Condylostoma could contain as many as six larvae. Related species may destroy many bivalve larvae in nature. PMID- 17745326 TI - Influence of Genetic Strain and Environment on the Protein Content of Pulses. AB - About 100 pure-bred samples of nine varieties of pulses raised in different state agricultural farms of India in 1957, when analyzed, indicated variations in the protein content of a single variety extending up to 60 percent in some cases, depending upon the strain and the locality where grown. PMID- 17745328 TI - Equipment. PMID- 17745329 TI - Why Not "Get Lost?". PMID- 17745330 TI - Why Not "Get Lost?". PMID- 17745331 TI - This week in science. PMID- 17745332 TI - Clean thoughts on clean air. PMID- 17745333 TI - Protecting the Environment: EPA's Role. PMID- 17745334 TI - Protecting the Environment: EPA's Role. PMID- 17745335 TI - Protecting the Environment: EPA's Role. PMID- 17745336 TI - Protecting the Environment: EPA's Role. PMID- 17745338 TI - Corrections and clarifications. AB - In the table in the article "Can sustainable farming win the battle of the bottom line?" by Bob Holmes (Environment & the Economy, 25 June, p. 1893), the second and third lines in the legend should have read, "Alt. #1: conventional corn soybean rotation with reduced tillage. Alt. #2: organic corn-beans-(wheat + clover)-clover-corn rotation with reduced tillage." PMID- 17745337 TI - Protecting the Environment: EPA's Role. PMID- 17745339 TI - Sciencescope. PMID- 17745340 TI - Russian science aid falls short. PMID- 17745341 TI - Wanted: a few thousand good reviewers. PMID- 17745342 TI - Chemistry community swarms into windy city. AB - Two times each year, legions of chemists gather in North America for a massive meeting to discuss the state of the art in their science. The second of this year's get-togethers occurred 2 weeks ago, when the 206th national meeting of the American Chemical Society (ACS) drew about 13,000 chemists, scientists, and onlookers to Chicago. Researchers shared 4800 or so papers and posters on everything from making waste plastic into fuel oil to the chemical basis for the stench of ginkgo fruit to modeling the first instants of photosynthesis. PMID- 17745343 TI - Bits of the lower mantle found in brazilian diamonds. PMID- 17745344 TI - Gordon conferences picks new head. PMID- 17745345 TI - U.k changes mind about malaria vaccine. PMID- 17745346 TI - A face-off on Mars. PMID- 17745347 TI - Fullerene Super-conductors Heat up edited by JOHN TRAVIS. PMID- 17745349 TI - Good booze and the higgs boson. PMID- 17745348 TI - Species Protection Moves at Snail's Pace. PMID- 17745350 TI - Phase boundaries and mantle convection. PMID- 17745351 TI - Physical Chemistry of the H2SO4/HNO3/H2O System: Implications for Polar Stratospheric Clouds. AB - Polar stratospheric clouds (PSCs) play a key role in stratospheric ozone depletion. Surface-catalyzed reactions on PSC particles generate chlorine compounds that photolyze readily to yield chlorine radicals, which in turn destroy ozone very efficiently. The most prevalent PSCs form at temperatures several degrees above the ice frost point and are believed to consist of HNO(3) hydrates; however, their formation mechanism is unclear. Results of laboratory experiments are presented which indicate that the background stratospheric H(2)SO(4)/H(2)O aerosols provide an essential link in this mechanism: These liquid aerosols absorb significant amounts of HNO(3) vapor, leading most likely to the crystallization of nitric acid trihydrate (NAT). The frozen particles then grow to form PSCs by condensation of additional amounts of HNO(3) and H(2)O vapor. Furthermore, reaction probability measurements reveal that the chlorine radical precursors are formed readily at polar stratospheric temperatures not just on NAT and ice crystals, but also on liquid H(2)SO(4) solutions and on solid H(2)SO(4) hydrates. These results imply that the chlorine activation efficiency of the aerosol particles increases rapidly as the temperature approaches the ice frost point regardless of the phase or composition of the particles. PMID- 17745352 TI - A detailed map of the 660-kilometer discontinuity beneath the izu-bonin subduction zone. AB - Dynamical processes in the Earth's mantle, such as cold downwelling at subduction zones, cause deformations of the solid-state phase change that produces a seismic discontinuity near a depth of 660 kilometers. Observations of short-period, shear to-compressional wave conversions produced at the discontinuity yield a detailed map of deformation beneath the Izu-Bonin subduction zone. The discontinuity is depressed by about 60 kilometers beneath the coldest part of the subducted slab, with a deformation profile consistent with the expected thermal signature of the slab, the experimentally determined Clapeyron slope of the phase transition, and the regional tectonic history. PMID- 17745353 TI - Comparisons between seismic Earth structures and mantle flow models based on radial correlation functions. AB - Three-dimensional numerical simulations were conducted of mantle convection in which flow through the transition zone is impeded by either a strong chemical change or an endothermic phase change. The temperature fields obtained from these models display a well-defined minimum in the vertical correlation length at or near the radius where the barrier is imposed, even when the fields were filtered to low angular and radial resolutions. However, evidence for such a feature is lacking in the shear-velocity models derived by seismic tomography. This comparison suggests that any stratification induced by phase or chemical changes across the mid-mantle transition zone has a relatively small effect on the large scale circulation of mantle material. PMID- 17745354 TI - Late cretaceous precessional cycles in double time: a warm-Earth milankovitch response. AB - Late Cretaceous climatic cycles are reflected in lithological and magnetic variations in carbonate sediments from South Atlantic Deep-Sea Drilling Project site 516F at a paleolatitude of roughly 30 degrees S. Magnetic susceptibility cycles 20 to 60 centimeters in length appear to be controlled by the precession of the equinoxes. Cyclicity is particularly robust within a 24-meter interval in the lower Campanian, where overtone spectral peaks are observed as well as secondary susceptibility maxima within individual precession cycles. One model for this behavior is that sedimentation in the narrow Cretaceous South Atlantic was controlled by equatorial climate dynamics, with the precessional insolation signal rectified by the large land masses surrounding the ocean basin. PMID- 17745355 TI - Probing chemical reactions: evidence for exploration of an excited potential energy surface at thermal energies. AB - The reaction K + NaBr --> KBr + Na is probed during the reactive collision by a continuous wave laser tuned to frequencies not resonant with excitation in either reagents or products. Transient [K..Br..Na] absorbs a laser photon giving [K..Br..Na](*), which can decompose to Na(*) + KBr. Emission from excited Na(*) at the sodium D lines provides direct evidence of laser absorption during the reaction. Different excitation spectra were observed, depending on which sodium D line was monitored. This difference is explicable if, in the absence of the laser, the reaction flux partially bifurcates to a second potential energy surface during the reaction. PMID- 17745356 TI - Why silicon is hard. AB - Compared with pure metals and ionic salts, covalent solids such as silicon are hard and brittle because dislocations do not move in them except at high temperatures. A satisfactory explanation for this behavior has been lacking in spite of its great importance for the mechanics of materials and structures. It is shown here that the critical atomic process leading to the observed brittleness is analogous to a chemical substitution reaction. Analysis of this analogy with the aid of a correlation diagram yields the observed high resistive stress and high activation energy. When a kink on a dislocation line moves, it breaks the atomic bonding symmetry, a forbidden process. PMID- 17745357 TI - Visionary and mobilizer. PMID- 17745359 TI - Vignette: leo szilard. PMID- 17745358 TI - An intricate ecosystem. PMID- 17745360 TI - Fisheries oceanography. PMID- 17745361 TI - The new microscopy. PMID- 17745362 TI - Products & materials. PMID- 17745364 TI - Publications Received. PMID- 17745363 TI - Boston, 1953. PMID- 17745365 TI - Meetings & Conferences. PMID- 17745366 TI - The Common Ground of Science and Politics. PMID- 17745367 TI - Association Business. PMID- 17745368 TI - Public Information at St. Louis. PMID- 17745370 TI - Reports of Sections and Societies. PMID- 17745369 TI - A Report of the St. Louis Meeting December 26-31, 1952. PMID- 17745371 TI - THE CHANGE FROM THE OLD TO THE NEW BOTANY IN THE UNITED STATES. PMID- 17745372 TI - THE SIMULIUM-PELLAGRA PROBLEM IN ILLINOIS, U. S. A. PMID- 17745373 TI - EOANTHROPUS DAWSONI. PMID- 17745374 TI - THE YALE PERUVIAN EXPEDITION OF 1912. PMID- 17745375 TI - A NATIONAL UNIVERSITY AT WASHINGTON. PMID- 17745376 TI - NEO-VITALISM AND THE LOGIC OF SCIENCE. PMID- 17745377 TI - A PROTEST. PMID- 17745378 TI - THE EFFECT OF ANESTHETICS UPON PERMEABILITY. PMID- 17745379 TI - PARTIAL SEX-LINKAGE IN THE PIGEON. PMID- 17745381 TI - THE AMERICAN SOCIETY OF NATURALISTS. PMID- 17745380 TI - EXPERIMENTS SHOWING THAT COMPLETE RELATIVITY DOES NOT EXIST IN ELECTROMAGNETIC INDUCTION. PMID- 17745382 TI - THE AMERICAN MATHEMATICAL SOCIETY. PMID- 17745384 TI - This week in science. PMID- 17745383 TI - THE OHIO ACADEMY OF SCIENCE. PMID- 17745385 TI - Opportunities in agricultural research. PMID- 17745386 TI - Civilian technology development. PMID- 17745387 TI - "Progenote" or "protogenote"? PMID- 17745388 TI - In reply: quasicrystal publications. PMID- 17745389 TI - Quasicrystal publications. PMID- 17745390 TI - Information decontrol urged. PMID- 17745391 TI - Fast, Cheap, and Out of Control: The visionaries at the MIT Insect Lab are out to revolutionize artificial intelligence, reform the space program, and mow your lawn with swarms of microminiaturized "gnat robots". PMID- 17745392 TI - Science for nonscience majors. PMID- 17745393 TI - EARTHWINDS Around the World. PMID- 17745395 TI - Climate Experts Say It Again: Greenhouse is Real. PMID- 17745394 TI - Baltimore assembles team. PMID- 17745396 TI - Drugs and biotechnology. PMID- 17745398 TI - A sailing race to Mars? PMID- 17745397 TI - Finland to Join CERN. PMID- 17745399 TI - Citation impact on the Coast. PMID- 17745400 TI - DOE Fills Biology Post. PMID- 17745401 TI - The superswell and mantle dynamics beneath the South pacific. AB - The region of sea floor beneath French Polynesia (the "Superswell") is anomalous in that its depth is too shallow, flexural strength too weak, seismic velocity too slow, and geoid anomaly too negative for its lithospheric age as determined from magnetic isochrons. These features evidently are the effect of excess heat and extremely low viscosity in the upper mantle that maintain a thin lithospheric plate so easily penetrated by volcanism that 30 percent of the heat flux from all hot spots is liberated in this region, which constitutes only 3 percent of the earth's surface. The low-viscosity zone may facilitate rapid plate motion and the development of small-scale convection. A possible heat supply for the Superswell is a mantle reservoir enriched in radioactive isotopes as suggested by the geochemical signature of lavas from Superswell volcanoes. PMID- 17745402 TI - Radar reflectivity of titan. AB - The present understanding of the atmosphere and surface conditions on Saturn's largest moon, Titan, including the stability of methane, and an application of thermodynamics leads to a strong prediction of liquid hydrocarbons in an ethane methane mixture on the surface. Such a surface would have nearly unique microwave reflection properties due to the low dielectric constant. Attempts were made to obtain reflections at a wavelength of 3.5 centimeters by means of a 70-meter antenna in California as the transmitter and the Very Large Array in New Mexico as the receiving instrument. Statistically significant echoes were obtained that show Titan is not covered with a deep, global ocean of ethane, as previously thought. The experiment yielded radar cross sections normalized by the Titan disk of 0.38 +/- 0.15, 0.78 +/- 0.15, and 0.25 +/- 0.15 on three consecutive nights during which the sub-Earth longitude on Titan moved 50 degrees. The result for the combined data for the entire experiment is 0.35 +/- 0.08. The cross sections are very high, most consistent with those of the Galilean satellites; no evidence of the putative liquid ethane was seen in the reflection data. A global ocean as shallow as about 200 meters would have exhibited reflectivities smaller by an order of magnitude, and below the detection limit of the experiment. The measured emissivity at similar wavelengths of about 0.9 is somewhat inconsistent with the high reflectivity. PMID- 17745403 TI - Coincidence Counting in Time-of-Flight Mass Spectrometry: A Test for Chemical Microhomogeneity. AB - Coincidence counting techniques have been combined with time-of-flight mass spectrometry in the examination of surfaces for chemical microhomogeneity. A mathematical formalism was developed to describe the principles underlying this coincidence counting technique and was used to produce a quantitative method for handling the data obtained. This technique of testing for chemical homogeneity has been demonstrated with a sample that consists of a physical mixture of polystyrene and crystals of NaF which were tenths of micrometers in diameter. Ultimately this approach is expected to be useful for the routine testing of surfaces for chemical homogeneity at the level of tens of nanometers. PMID- 17745404 TI - Image reconstruction of the interior of bodies that diffuse radiation. AB - A method for reconstructing images from projections is described. The unique aspect of the procedure is that the reconstruction of the internal structure can be carried out for objects that diffuse the incident radiation. The method may be used with photons, phonons, neutrons, and many other kinds of radiation. The procedure has applications to medical imaging, industrial imaging, and geophysical imaging. PMID- 17745405 TI - Ultradeep (greater than 300 kilometers), ultramafic upper mantle xenoliths. AB - Geophysical discontinuities in Earth's upper mantle and experimental data predict the structural transformation of pyroxene to garnet and the solid-state dissolution of pyroxene into garnet with increasing depth. These predictions are indirectly verified by omphacitic pyroxene exsolution in pyropic garnet-bearing xenoliths from a diamondiferous kimberlite. Conditions for silicon in octahedral sites in the original garnets are met at pressures greater than 130 kilobars, placing the origin of these xenoliths at depths of 300 to 400 kilometers. These ultradeep xenoliths support the theory that the 400-km seismic discontinuity is marked by a transition from peridotite to eclogite. PMID- 17745406 TI - Increase in the stratospheric background sulfuric Acid aerosol mass in the past 10 years. AB - Data obtained from measurements of the stratospheric aerosol at Laramie, Wyoming (41 degrees N), indicate that the background or nonvolcanic stratospheric sulfuric acid aerosol mass at northern mid-latitudes has increased by about 5 +/- 2 percent per year during the past 10 years. Whether this increase is natural or anthropogenic could not be determined at this time because of inadequate information on sulfur sources, in particular, carbonyl sulfide, which is thought to be the dominant nonvolcanic source of stratospheric sulfuric acid vapor. An increase in stratospheric sulfate levels has important climatic implications as well as heterogeneous chemical effects that may alter the concentration of stratospheric ozone. PMID- 17745407 TI - Faults in the mojave desert, california, as revealed on enhanced landsat images. AB - Previously unknown strike-slip and normal faults in the central and eastern Mojave Desert have been revealed on Landsat Thematic Mapper images enhanced by four-component processing. This method provides color images on which lithologies are discriminated by their contrasting absorption and reflection, primarily at infrared wavelengths and particularly with regard to their ferric iron, ferrous iron, and hydroxyl contents, while retaining landform depiction. These discriminants represent a new type of geophysical display for geologic mapping in regions of well-exposed bedrock. Faults are revealed on the images by abrupt spectral and textural contrasts that coincide with aligned topographic features. The newly discovered faults form part of an extensive regional network of right shear that connects faults in the Death Valley region with the San Andreas fault system. They support a heterogeneous strain model for late Cenozoic tectonic evolution of the region. Regional structural relations indicate a westward migration of the locus of strain through time. Some of the newly identified faults bound blocks that have experienced contrasting rotational histories since early Miocene time. PMID- 17745408 TI - Marmots. Social Behavior and Ecology. David P. Barash. Stanford University Press, Stanford, CA, 1989. xviii, 360 pp., illus. $49.50. PMID- 17745409 TI - Technical Workers in an Advanced Society. The Work, Careers and Politics of French Engineers. Stephen Crawford. Cambridge University Press, New York, and Editions de la Maison des Sciences de l'Homme, Paris, 1989, viii, 284 pp. $49.50. PMID- 17745410 TI - Ecology and Natural History of Tropical Bees. David W. Roubik. Cambridge University Press, New York, 1989. x, 514 pp., illus. $69.50. Cambridge Tropical Biology Series. PMID- 17745412 TI - Products & materials. PMID- 17745411 TI - Electric Fields in Vertebrate Repair. Natural and Applied Voltages in Vertebrate Regeneration and Healing. Richard B. Borgens, Kenneth R. Robinson, Joseph W. Vanable, Jr., and Michael E. McGinnis, with Colin D. McCaig. Liss, New York, 1989. xxiv, 310 pp., illus. $69.50. PMID- 17745413 TI - THE GOOD ENGINEERING TEACHER, HIS PERSONALITY AND TRAINING. PMID- 17745414 TI - PRACTICAL WORK IN SCIENCE TEACHING. PMID- 17745415 TI - THE MINING CONGRESS AND EXPOSITION IN PHILADELPHIA. PMID- 17745416 TI - MEMORIAL TO SIR WILLIAM LOGAN. PMID- 17745418 TI - DOES A LOW-PROTEIN DIET PRODUCE RACIAL INFERIORITY? PMID- 17745417 TI - THE WORD "SELVA" IN GEOGRAPHIC LITERATURE. PMID- 17745419 TI - THE SPIRIT OF AGRICULTURAL EDUCATION. PMID- 17745421 TI - THE ORIENTAL CYCADS IN THE FIELD. PMID- 17745420 TI - THE TARIFF ON BOOKS. PMID- 17745422 TI - TWENTY-FIRST ANNUAL MEETING OF THE SOCIETY FOR THE PROMOTION OF ENGINEERING EDUCATION. PMID- 17745423 TI - THE LIFE CYCLE OF THE PROTOZOA. PMID- 17745424 TI - PRUNING THE ACADEMIC TREE. PMID- 17745425 TI - COOPERATION OF THE GOVERNMENT IN SCIENTIFIC WORK. PMID- 17745426 TI - WEATHERWAX ON MAIZE ENDOSPERM. PMID- 17745427 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17745429 TI - NEW OCCURRENCE OF THE BELT TERRANE IN MONTANA. PMID- 17745428 TI - THE SCALES OF THE FOSSIL FISH EOBRYCON. PMID- 17745430 TI - SPARKLESS SPARKS. PMID- 17745431 TI - REPORT OF THE TREASURER FOR 1922. PMID- 17745432 TI - FINANCIAL REPORT OF THE PERMANENT SECRETARY FOR THE FISCAL YEAR, 1922. PMID- 17745434 TI - CONFIRMATION OF THE DISCOVERY OF THE INFLUENZA BACILLUS. PMID- 17745433 TI - NOTICE OF NEW GIGANTIC FOSSILS. PMID- 17745435 TI - Action of Microphytes on Solid Compounds of Arsenic: A Recapitulation, by Dr. B. Gosio. PMID- 17745436 TI - ARSENICAL POISONING FROM DOMESTIC FABRICS. PMID- 17745437 TI - A PROBLEM IN PHYSICS. PMID- 17745438 TI - The Loup Rivers in Nebraska. PMID- 17745439 TI - PROFESSOR GEIKIE ON THE GLACIAL PERIOD. PMID- 17745440 TI - Origin of the Frigid Period in the Northern Hemisphere. PMID- 17745441 TI - Electricity in Agriculture. PMID- 17745442 TI - SCIENCE NEWS. PMID- 17745443 TI - THE ORIGIN, GROWTH AND SIGNIFICANCE OF THE MENTAL HYGIENE MOVEMENT. PMID- 17745444 TI - PERIODICALS FOR ELECTRICAL ENGINEERS. PMID- 17745445 TI - EFFECT OF WATER ON TRIBOELECTRIC LUMINESCENCE WITH MERCURY IN GLASS. PMID- 17745446 TI - THE MAGNETIC POLES OF THE EARTH AND THE BIRTH OF THE MOON. PMID- 17745447 TI - MORE ABOUT A UNIFORM BIBLIOGRAPHIC SYSTEM. PMID- 17745448 TI - GAS DISCHARGE WAVE-LENGTH LIST IN THE EXTREME ULTRA-VIOLET. PMID- 17745449 TI - MARMOSA AS A STOWAWAY AGAIN. PMID- 17745450 TI - ATTACK BY A SCREECH-OWL. PMID- 17745451 TI - A PRACTICAL FLAGELLA AND CAPSULE STAIN FOR BACTERIA. PMID- 17745452 TI - A SIMPLE METHOD FOR THE GERMINATION OF OOSPORES OF SCLEROSPORA GRAMINICOLA. PMID- 17745453 TI - AN ATTEMPT TO PRODUCE MUTATIONS BY THE USE OF ELECTRICITY. PMID- 17745454 TI - THE FECUNDITY OF THE OYSTER. PMID- 17745455 TI - THE OIL ABSORPTION OF SHELL EGGS. PMID- 17745456 TI - QUEEN'S NEW TRIPLE-PLATE TOEPLER-HOLTZ MACHINE. PMID- 17745457 TI - WATER-SPOUTS. PMID- 17745458 TI - WYNNE'S ELECTRIC TRAMWAY SYSTEM. PMID- 17745459 TI - AMENDED ORTHOGRAPHY. PMID- 17745460 TI - Sea-Water and the Nutrition of Marine Animals. PMID- 17745462 TI - Means of increasing the Accuracy of locating Vessels at Sea. PMID- 17745461 TI - HEALTH MATTERS. PMID- 17745463 TI - INDUSTRIAL NOTES. PMID- 17745465 TI - THE SCIENTIFIC ASPECT OF MODERN MEDICINE. PMID- 17745464 TI - Storage-Batteries. PMID- 17745466 TI - HISTORIES AND BIBLIOGRAPHIES OF PHYSICS. PMID- 17745467 TI - UNIVERSITY REGISTRATION STATISTICS. PMID- 17745468 TI - NEW DEPARTURES IN THE BIBLIOGRAPHICAL WORK OF THE CONCILIUM BIBLIOGRAPHICUM. PMID- 17745469 TI - THE STRATIGRAPHIC POSITION OF THE JUDITH RIVER BEDS. A CORRECTION OF MR. HATCHER'S CORRECTION. PMID- 17745470 TI - NATURAL HISTORY IN ENGLAND. PMID- 17745471 TI - THE PRICKLES OF XANTHOXYLUM. PMID- 17745472 TI - THE CARNEGIE INSTITUTION. PMID- 17745473 TI - TREE TRUNKS FOUND WITH MASTODON REMAINS. PMID- 17745474 TI - THE FIRST USE OF MAMMALS AND MAMMALIANS. PMID- 17745475 TI - THE STARTING POINT FOR GENERIC NOMENCLATURE IN BOTANY. PMID- 17745477 TI - THE CONVOCATION OF SCIENTIFIC SOCIETIES. PMID- 17745476 TI - MOSQUITO DEVELOPMENT AND HIBERNATION. PMID- 17745478 TI - An Academic Question. PMID- 17745479 TI - Structure of Physical Science. PMID- 17745480 TI - News of Science. PMID- 17745481 TI - Effect of Genes on Birefringence End-Point Temperature of Starch Grains in Maize. PMID- 17745483 TI - Meetings and Societies. PMID- 17745482 TI - Nutrition of Plant-Sucking Hemiptera. PMID- 17745485 TI - Diffraction Patterns. PMID- 17745484 TI - Biology of Schizophrenia. PMID- 17745486 TI - No Visa Difficulties. PMID- 17745488 TI - EQUIPMENT NEWS. PMID- 17745487 TI - Biology of Schizophrenia. PMID- 17745489 TI - ELIHU THOMSON'S INTEREST IN RESEARCH. PMID- 17745491 TI - OBITUARY. PMID- 17745490 TI - ELIHU THOMSON THE SCIENTIST. PMID- 17745492 TI - WILLIAM BREWSTER: NEW ENGLAND NATURALIST. PMID- 17745493 TI - THE FERMENTATION TEST FOR THIAMIN. PMID- 17745494 TI - ALEPRIC AND ALEPRYLIC ACIDS, NEW HOMOLOGS OF CHAULMOOGRIC ACID. PMID- 17745495 TI - THE INFLUENCE OF SOME DIGESTIVE FERMENTS ON THE EXPERIMENTAL CROWN-GALL. PMID- 17745496 TI - FINANCIAL REPORTS OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE AT THE RICHMOND MEETING. PMID- 17745498 TI - DROPLET FISSION OF URANIUM AND THORIUM NUCLEI. PMID- 17745497 TI - THE SOCIETY OF THE SIGMA XI. PMID- 17745499 TI - POSSIBLE AVITAMINOSIS K PRODUCED IN MICE BY DIETARY MEANS. PMID- 17745500 TI - THE SODIUM FACTOR OF THE ADRENAL. PMID- 17745501 TI - A MODIFICATION OF THE SET-UP FOR WICK CULTURE. PMID- 17745502 TI - IMMUNIZATION TO INFECTIOUS MYXOMATOSIS. PMID- 17745503 TI - THE DUTY AND RESPONSIBILITY OF THE UNIVERSITY IN MEDICAL EDUCATION. PMID- 17745504 TI - THE NEW DEFINITION OF THE CULTIVATED MAN. PMID- 17745505 TI - THE GRAND GULF FORMATION. PMID- 17745506 TI - ANSWER TO PROFESSOR COCKERELL, REGARDING HIGHER EDUCATIONAL INSTITUTIONS OF NEW MEXICO. PMID- 17745507 TI - THE PROPOSED BIOLOGICAL STATIONS AT THE TORTUGAS. PMID- 17745508 TI - SOME OF THE DANGERS OF FORMAL. PMID- 17745510 TI - OPENING OF THE LAKE LABORATORY OF THE OHIO STATE UNIVERSITY. PMID- 17745509 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17745511 TI - Occupational lead exposure: what are the risks? PMID- 17745512 TI - Is evacuation the best policy? PMID- 17745513 TI - Erratum. AB - In the report by Simpson et al., "Saturnian trapped radiation and its absorption by satellites and rings: The first results from Pioneer 11" (25 Jan., p. 411), in Fig. 1B the right hand scale of flux (for the electrons with energies > 3.4 million electron volts) should be multiplied by a factor of 10 so that the maximum flux measured by the electron current detector is 3 x 10(6) cm(-2) sec( 1). Furthermore, in reference 9, the following citation was inadvertently omitted: M. H. Acuna and N. F. Ness, ibid., p. 444. PMID- 17745515 TI - Energy policies of the United States and u.s.s.R. PMID- 17745514 TI - Scanner development. PMID- 17745516 TI - Breeder reactors in france. AB - France relies on nuclear power as an important part of her energy program. Anticipating problems with the availability of natural uranium before the year 2020, the French have been pursuing a three-stage program of development of breeder reactors. The third reactor in this program, the near-commercial plant Super Phenix Mark I, is expected to reach power operation in 1983. Although there are still some uncertainties, particularly about the date when the breeder will become competitive with other energy sources, the outlook is considered favorable and preliminary designs for commercial plants are under way. PMID- 17745517 TI - International politics and science: frank press in Venezuela. PMID- 17745519 TI - Proxmire reenters the ring after scientist lands a hit. PMID- 17745518 TI - MX on Land or Sea? PMID- 17745520 TI - Controversial Scientist Considers Leaving NCI. PMID- 17745521 TI - SST Supporters Fly Above the Economic Fray. PMID- 17745522 TI - Texas puts together winning fusion team. PMID- 17745523 TI - East coast maps to alert industry to ecology conflict. PMID- 17745525 TI - The 1980 pittsburgh conference: a special instrumentation report. PMID- 17745524 TI - R & d will share in budget cuts. PMID- 17745526 TI - Portable elemental analyzers pushed. PMID- 17745527 TI - IC Versatility Promotes Competition. PMID- 17745528 TI - New tool to monitor sulfuric Acid emissions. PMID- 17745529 TI - Video--a new approach to chart recorders. PMID- 17745531 TI - Fourier transform comes to photoacoustic spectroscopy. PMID- 17745530 TI - A New Interferometer for Inexpensive FT-IR. PMID- 17745532 TI - Antecedents in meteorology. PMID- 17745533 TI - O-type stars. PMID- 17745534 TI - A plant family. PMID- 17745535 TI - Binocularity. PMID- 17745536 TI - Convection in a rotating layer: a simple case of turbulence. AB - Convection in a layer heated from below and rotating about a vertical axis exhibits a unique phenomenon in fluid dynamics in that the small-amplitude motion is governed by random effects in both its spatial and its time dependence. A simple theoretical description of the phenomenon is compared with laboratory observations. A more detailed mathematical description appears to be feasible because of the weakly nonlinear nature of the problem. PMID- 17745537 TI - Evolutionary implications of pliocene hominid footprints. AB - Hominid footprints discovered at the Pliocene (3.6 to 3.8 million years ago) site of Laetoli in northern Tanzania represent the earliest evidence of bipedalism in human evolution. This new evidence emphasizes the mosaic pattern of human evolution. PMID- 17745538 TI - Differential avoidance of mimetic salamanders by free-ranging birds. AB - Members of a free-ranging avian community avoided the mimetic morph of the salamander Plethodon cinereus significantly more often than a nonmimetic morph when offered with the model eft stage of Notophthalmus viridescens and the palatable salamander Desmognathus ochrophaeus. This is apparently the first demonstration of the efficacy of mimetic coloration of salamanders to uncaged birds. PMID- 17745539 TI - Organelle alteration as a mechanism for maternal inheritance. AB - An ultrastructural study of pollen-derived plants and normal microspore development indicates that chloroplasts and mitochondria are physically altered during microsporogenesis. These changes appear to debilitate the organelle so that only chloroplasts and mitochondria of the female parent are contributed to the offspring. PMID- 17745541 TI - PRODUCTS and MATERIALS. PMID- 17745540 TI - Preschool programs and later school competence of children from low-income families. AB - At follow-up in 1976, low-income children who had attended infant and preschool programs in the 1960's had significantly higher rates of meeting school requirements than did controls, as measured by lower frequency of placement in special education classes and of being retained in grade (held back). PMID- 17745542 TI - Peregrine falcon protection. PMID- 17745543 TI - World War II Nuclear Bomb Projects. PMID- 17745545 TI - The annual meeting. PMID- 17745544 TI - World War II Nuclear Bomb Projects. PMID- 17745546 TI - Past glacial activity in the canadian high arctic. AB - Field observations on northeast Ellesmere Island indicate that the maximum advance of the northwest Greenland Ice Sheet was about 100 kilometers beyond its present margin. This occurred before the outermost Ellesmere Island ice advance, which took place more than 30,000 years before present (B.P.). Recession from the Ellesmere Island ice margin began at least 28,000 to 30,000 and possibly more than 35,000 years B.P. During this sequence of glacial events, significant land areas remained free of ice. The late Wisconsin ice extent along both northeast Ellesmere Island and northwest Greenland was extremely limited, leaving an ice free corridor along Kennedy and Robeson channels. Recession from these ice margins is indicated by initial postglacial emergence around 8100 to 8400 years B.P. The relatively minor extent of late Wisconsin ice in the High Arctic probably reflects a period of extreme aridity occasioned by the buildup of the Laurentide Ice Sheet to the south. PMID- 17745547 TI - Guillemin and schally: the years in the wilderness. PMID- 17745548 TI - Navy meeting drifts on a sea of unanswered questions. PMID- 17745549 TI - Congressional investigators sniff out unused federal lab space. PMID- 17745550 TI - NCI's Retrospective Look at Laetrile Seems Doomed to Fail. PMID- 17745551 TI - MIT Scientist to Head FDA's Bureau of Foods. PMID- 17745552 TI - March of dimes denies giving in to antiabortionists. PMID- 17745553 TI - Erratum. AB - The correct legend for the cover of the 31 March 1978 issue of Science is as follows: Hindfoot prints of a 6-hydroxydopamine-treated rat. Although typically akinetic when it is induced to walk by atropine, the rat's gait is characterized by short steps that may be analogous to that of some Parkinson patients. Here the rat has just been placed on the ground, where it first assumed a broad base of support with the hind legs, then brought its feet closer together and walked forward. [Timothy Schallert, University of Illinois at Urbana-Champaign, Champaign]. PMID- 17745554 TI - Singing styles and human cultures: how are they related? PMID- 17745555 TI - Kenneth E. Boulding, President-Elect of the AAAS. PMID- 17745556 TI - 1977 report of the executive officer. PMID- 17745557 TI - Insect physiology. PMID- 17745558 TI - Physiologists' recollections. PMID- 17745559 TI - Protein synthesis. PMID- 17745560 TI - Amphibian nervous system. PMID- 17745561 TI - North american prehistory. PMID- 17745562 TI - Forest floor leaching: contributions from mineral, organic, and carbonic acids in new hampshire subalpine forests. AB - Analyses of soil water and groundwater samples from a high-elevation coniferous ecosystem in New England indicate that sulfate anions supply 76 percent of the electrical charge balance in the leaching solution. This result implies that atmospheric inputs of sulfuric acid provide the dominant source of both H(+) for cation replacement and mobile anions for cation transport in subalpine soils of the northeastern region affected by acid precipitation. In soils of relatively unpolluted regions, carbonic and organic acids dominate the leaching processes. PMID- 17745563 TI - Photocontrol of boron metabolism in sea grasses. AB - Boron is taken up in the dark and is excreted in response to light by the leaves of the marine vascular plant, Halophila engelmannii Ascherson. This phenomenon makes possible the study of boron metabolism in a higher plant without the stress of boron deficiency. Dependence of boron excretion on photosynthetic CO(2) fixation suggests that an organoboron complex between boron and a newly formed carbon compound from photosynthesis is selectively excreted. PMID- 17745564 TI - Avian eggs: thermoregulatory value of very high near-infrared reflectance. AB - Studies of the spectral reflectance of the eggs of 25 species of birds from nine families disclosed uniformly high reflectance (often above 90 percent) in the near infrared. This property is associated with the presence of the eggshell pigments protoporphyrin and the bilins. These pigments allow coloration for cryptic or other purposes with minimum solar heating, a combination not possible with the melanin pigments typical of vertebrates. PMID- 17745565 TI - Night-Shocker: Predatory Behavior of the Pacific Electric Ray (Torpedo californica). AB - Diving observations off Santa Barbara, California, indicate that Pacific electric rays (Torpedo californica) enter inshore reefs at night and actively prey on fish with the aid of powerful electric discharges. PMID- 17745566 TI - Morphine tolerance: is there evidence for a conditioning model? PMID- 17745567 TI - Sympatric speciation: evidence? PMID- 17745568 TI - THE AMERICAN CHEMIST AND THE WAR'S PROBLEMS. PMID- 17745569 TI - DEATH RATES AND EXPECTATION OF LIFE. PMID- 17745570 TI - THE IROQUOIS INDIAN GROUPS OF THE NEW YORK STATE MUSEUM. PMID- 17745571 TI - PUBLIC HEALTH WORK AND MEDICAL PRACTISE. PMID- 17745572 TI - NOMENCLATORIAL CONSISTENCY? PMID- 17745573 TI - THE CURRENT "DEFINITIONS" OF ENERGY. PMID- 17745574 TI - THERMOMETER SCALES. PMID- 17745576 TI - PERMEABILITY AND VISCOSITY. PMID- 17745575 TI - UNITS OF FORCE. PMID- 17745577 TI - POLLEN STERILITY IN RELATION TO CROSSING. PMID- 17745578 TI - ANTHROPOLOGY AT THE WASHINGTON MEETING. PMID- 17745579 TI - THE STUDY OF GEOGRAPHY. PMID- 17745580 TI - ITALIAN MEDICAL PSYCHOLOGY. PMID- 17745581 TI - MINERAL PHYSIOLOGY AND PHYSIOGRAPHY. PMID- 17745582 TI - REMSEN'S ELEMENTS OF CHEMISTRY. PMID- 17745584 TI - ERA and the AAAS. PMID- 17745583 TI - Energy policy and the quality of life. PMID- 17745585 TI - ERA and the AAAS. PMID- 17745586 TI - Carcinogens by fiat? PMID- 17745587 TI - A very human business. PMID- 17745588 TI - Color and constitution: one hundred years of research. AB - Useful theories and models of the color and constitution of unsaturated organic compounds have been sought for more than a century. The promises of quantum chemistry have not yet been realized satisfactorily. The polymethine concept, a modern chemical theory of constitution, is an auspicious development. PMID- 17745589 TI - Chemical ecology: studies from East Africa. AB - The International Centre of Insect Physiology and Ecology (ICIPE), in Nairobi, provides a laboratory at which a multinational group of scientists pursues interdisciplinary research. In collaboration with their colleagues in biology, ICIPE chemists have characterized the sex pheromones of the tick which serves as a vector of East Coast fever and have identified a termite queen-cell-building pheromone. The structure of many anthropod defensive chemicals have been determined; most interesting of these are the trinervitenes, structurally novel diterpenoids from nasute termites. Several highly active insect antifeedants were discovered using a simple bioassay to screen selected East African plants. These antifeedants may provide leads for the development of new insect-control techniques. PMID- 17745590 TI - ABASS: Social Sciences Carving a Niche at the Academy. PMID- 17745592 TI - Coca proposed as prescription drug. PMID- 17745591 TI - Court Rules GE May Patent New Microorganism. PMID- 17745593 TI - DNA work to begin soon at fort detrick. PMID- 17745595 TI - Bicycling and health: braving bad air. PMID- 17745594 TI - U.s. Warns britain on reprocessing. PMID- 17745596 TI - FBI--Privacy Fight Flares Up. PMID- 17745597 TI - Historian of science States case for catching up on basic research. PMID- 17745598 TI - "New wave in academia" wipes out department at yale. PMID- 17745599 TI - Patent policy changes stir concern. PMID- 17745601 TI - Recapitulationism: issues evolutionary and philosophical. PMID- 17745600 TI - Analytical chemistry: using lasers to detect less and less. PMID- 17745602 TI - A view of edison. PMID- 17745603 TI - Research specialties. PMID- 17745604 TI - Archeoastronomy. PMID- 17745605 TI - Mnemonic processing. PMID- 17745606 TI - Ultraviolet-photoproduced organic solids synthesized under simulated jovian conditions: molecular analysis. AB - In an earlier paper, Khare and Sagan reported the production of a brownish polymeric material from the near-ultraviolet irradiation of simulated jovian atmospheres with a low hydrogen abundance. Examination of this product indicates that hydrogen sulfide is the initial photon acceptor; the powder resulting after extraction with benzene is 84 percent sulfur, largely S(8). In results reported here, the remaining 16 percent was pyrolyzed and then examined by gas chromatography-mass spectrometry. Pyrolysis at 450 degrees C yielded a series of alkanes, alkenes, C(3)-alkylbenzenes, aromatics, thiophenes, alkylthiophenes, alkylmercaptans, alkyldisulfides, together with the nitrogenous compounds hydrogen cyanide, methyl cyanide, alkylisothiocyanates, acrylonitrile, and allylisothiocyanates. Some of these compounds might be sought on Jupiter and Saturn and their satellites by remote infrared and ultraviolet spectroscopy and directly by entry probes. PMID- 17745607 TI - Phobos transit of Mars as viewed by the viking cameras. AB - A Viking orbiting spacecraft successfully obtained pictures of the martian satellite Phobos with Mars in the background. This is the first time that a single picture was obtained from a spacecraft which contained both a planet and a moon and had significant surface detail visible on both. The region of Mars below Phobos included volcanoes in the Tharsis Montes region. These pictures showed Phobos to be smaller than previously thought. The image of Phobos can be used as a control point to determine the map coordinates of surface features on Mars. PMID- 17745608 TI - Cardiac pacemaking. PMID- 17745609 TI - THE MOBILIZATION OF SCIENCE. PMID- 17745610 TI - SOME OBSTACLES IN THE PATH TOWARDS AN OPTIMUM DIET.II. PMID- 17745611 TI - RESOLUTIONS PASSED BY THE HOSPITAL BUREAU OF STANDARDS AND SUPPLIES. PMID- 17745612 TI - THE COPERNICAN QUADRICENTENNIAL CELEBRATION. PMID- 17745613 TI - THE MERCK INSTITUTE FOR THERAPEUTIC RESEARCH. PMID- 17745614 TI - THE NATIONAL ACADEMY OF SCIENCES. PMID- 17745615 TI - THE AMERICAN PHILOSOPHICAL SOCIETY. PMID- 17745617 TI - OPTICAL ILLUSIONS FROM TRAIN WINDOWS. PMID- 17745616 TI - NATIONAL LEARNED SOCIETY GROUPS AND THE PUBLIC INTEREST. PMID- 17745618 TI - TYPES OF ARGENTINIAN PLANTS OF SPEGAZZINI. PMID- 17745619 TI - ABNORMAL NITROGEN METABOLISM IN BURNS. PMID- 17745620 TI - THE ROLE OF "FOLIC ACID" AND BIOTIN IN THE UTILIZATION OF PANTOTHENIC ACID BY THE RAT. AB - The addition of succinylsulfathiazole to highly purified diets containing all dietary factors known to be required by the rat, including pantothenic acid, results in the appearance of signs of severe pantothenic acid deficiency, including achromotrichia and porphyrin-caked whiskers. These changes are accompanied by a marked reduction in the pantothenic acid content of the liver, and are corrected by the inclusion in such diets of crystalline biotin and "folic acid" concentrates. The utilization of pantothenic acid by the rat appears to depend on the availability of biotin and "folic acid." Under normal conditions these are supplied by the diet and synthesized by intestinal bacteria. A hypothesis is offered in explanation of the chromotrichial actions of "folic acid," biotin and p-aminobenzoic acid. PMID- 17745621 TI - THE USE OF FIBROUS SODIUM PECTATE AS A SUBSTITUTE FOR AGAR IN BACTERIOLOGICAL GELS. PMID- 17745622 TI - THE INTERNATIONAL AERONAUTICAL CONFERENCE AT MILAN. PMID- 17745623 TI - THE DANGER OF OVERSPECIALIZATION. PMID- 17745624 TI - THE CLOCKS OF THE GREENWICH AND U. S. NAVAL OBSERVATORIES. PMID- 17745626 TI - REASONS FOR BELIEVING IN AN ETHER. PMID- 17745625 TI - THE FIRST SPECIES RULE. PMID- 17745627 TI - SOME MUTUAL EFFECTS OF TREE-ROOTS AND GRASSES ON SOILS. PMID- 17745629 TI - LINNAeUS AND THE NEW YORK ACADEMY OF SCIENCES. PMID- 17745628 TI - BOTANICAL NOTES. PMID- 17745630 TI - Physician migration. PMID- 17745631 TI - Natural rubber production. PMID- 17745632 TI - Natural rubber production. PMID- 17745634 TI - The impact statement boondoggle. PMID- 17745633 TI - Timber management. PMID- 17745635 TI - Cancer institute: expert charges neglect of carcinogenesis studies. PMID- 17745636 TI - Clinical labs: bills aimed at correcting "massive" problems. PMID- 17745637 TI - NAE Elects 104 New Members. PMID- 17745638 TI - Clean air act: congress deliberates on amendments. PMID- 17745639 TI - Earthquakes: los angeles prediction suggests faults in federal policy. PMID- 17745640 TI - Earthquakes: an evacuation in china, a warning in california. PMID- 17745641 TI - Diabetic retinopathy: new ways to prevent blindness. PMID- 17745642 TI - Advanced storage batteries: progress, but not electrifying. PMID- 17745643 TI - New funding sparks battery research. PMID- 17745645 TI - Science ranked high in faculty survey. PMID- 17745644 TI - Congress praises fellows program. PMID- 17745646 TI - AAAS-AAS Workshop at Annual Meeting. PMID- 17745647 TI - Let SMC Do Your Reading. PMID- 17745648 TI - Locomotion in fluid media. PMID- 17745649 TI - Ecology: progress and self-criticism. PMID- 17745651 TI - Land snail biology. PMID- 17745650 TI - How roots work. PMID- 17745652 TI - Tropospheric halogen gases: inorganic and organic components. AB - Inorganic and organic components of the gaseous tropospheric halogens chlorine, bromine, and iodine have been simultaneously measured. At four diverse remote locations the organic component contained the bulk of the halogen mass, varied less than the inorganic component, and was comparable in concentration to the independently measured halocarbon component. PMID- 17745653 TI - Chemical Mass Balance of the Earth's Crust: The Calcium Dilemma (?) and the Role of Pelagic Sediments. AB - Chemical mass balance between igneous and sedimentary rocks is calculated by using a linear least squares method in which all chemical variables are evaluated simultaneously. Previous estimates of the average chemical composition of sedimentary rocks have shown excess calcium because of failure to accurately represent the composition and mass of pelagic sediments. PMID- 17745654 TI - Fly ash collected from electrostatic precipitators: microcrystalline structures and the mystery of the spheres. AB - Scanning electron micrographs demonstrate the presence of microcrystalline structures on the surface of coal-derived fly ash samples taken from electrostatic precipitator hoppers. Cenospheres (hollow spheres) were found to be packed with smaller cenospheres, which were also packed with spheres. Microspheres, apparently formed by uneven heating, are encapsulated in the parent sphere. Chemical analyses provide a basis for the postulation of a mechanism of formation for plerospheres (hollow spheres packed with spheres) and microcrystals. PMID- 17745656 TI - Stratospheric ozone effects on temperature. AB - Calculated surface temperature changes, DeltaT(8), due to stratospheric ozone depletion (at 35 degrees N latitude in April) are less than previously estimated and range between -0.6 and +0.9 degrees K. The sign of DeltaT(8), is determined by the surface albedo and the presence or absence of a low-lying particulate layer (heating with particles, cooling without particles). The calculations indicate that a 90 percent stratospheric ozone depletion does not cause the temperature inversion at the tropopause to vanish, although it is weakened substantially. PMID- 17745655 TI - Eleven-year variation in polar ozone and stratospheric-ion chemistry. AB - A mechanism for producing an 11-year oscillation in ozone over the polar caps is the modulation of galactic cosmic rays by the solar wind. This mechanism has been shown to give the observed phase in ozone oscillations and the correct qualitative dependence on latitude. However, the production of nitrogen atoms from cosmic-ray collisions seems inadequate to account for the ozone amplitude. Negative ions are also produced as a result of cosmic-ray ionization, and negative-ion chemistry may be of importance in the stratosphere. Specifically, NO(x)(-) may go through a catalytic cycle in much the same fashion as NO(x), but with the important distinction that it does not depend on oxygen atoms to complete the cycle. Estimates of the relevant rates of reaction suggest that negative ions may be especially important over the winter polar cap. PMID- 17745657 TI - Reproductive development in a female songbird: differential stimulation by quality of male song. AB - Female canaries exposed to playback of large repertoires of male songs built nests faster and laid more eggs than did those females exposed to smaller song repertoires: females are attentive to attributes of male song, and their choices have played a role in the evolution of oscine singing behaviors. PMID- 17745659 TI - New publications. PMID- 17745658 TI - Notes from the office of international science. PMID- 17745660 TI - THE OUTLOOK OF THE SECTION FOR EDUCATION. PMID- 17745661 TI - SECTION L, EDUCATION. PMID- 17745662 TI - THE AMERICAN FEDERATION OF TEACHERS OF THE MATHEMATICAL AND THE NATURAL SCIENCES. PMID- 17745663 TI - THE COLLEGE AND THE UNIVERSITY. PMID- 17745664 TI - COOPERATION IN SCIENTIFIC BIBLIOGRAPHY. PMID- 17745665 TI - THE INHERITANCE OF FLUCTUATING VARIATION. PMID- 17745666 TI - TO REDUCE SEASICKNESS TO A MINIMUM. PMID- 17745668 TI - THE SO-CALLED VOLCANO IN THE SANTA MONICA MOUNTAINS, NEAR LOS ANGELES, CALIFORNIA. PMID- 17745667 TI - COMPETITIVE ATHLETICS AND SCHOLARSHIP. PMID- 17745670 TI - ORGANIZATION OF A UTAH ACADEMY OF SCIENCES. PMID- 17745669 TI - JOINT RECOMMENDATIONS OF THE PHYSIOLOGICAL AND BIOCHEMICAL COMMITTEES ON PROTEIN NOMENCLATURE. PMID- 17745671 TI - THIRD SESSION OF THE GRADUATE SCHOOL OF AGRICULTURE. PMID- 17745672 TI - Letters to the Editor. PMID- 17745673 TI - Plotting Titration Data. PMID- 17745674 TI - Gea. Daughter of chaos. PMID- 17745675 TI - Randomized Cloud Seeding in Santa Barbara. PMID- 17745676 TI - Quantum Phenomena in Biology. PMID- 17745678 TI - $150,000 To Be Shared by Four Atoms for Peace Award Winners. PMID- 17745677 TI - Salary Report Presented by University Professors' Group. PMID- 17745679 TI - Improvement of High-School Chemistry Courses To Be Studied under Science Foundation Grant. PMID- 17745680 TI - Effect of Kinetin on Formation of Red Pigment in Seedlings of Amaranthus retroflexus. AB - Kinetin induces formation of red pigment in seedlings of Amaranthus retroflexus in the dark. This effect is similar to the light-induced formation of pigment. Light and kinetin do not act in a simple additive way. The pigment is not an anthocyanin, and its formation is not affected by inhibitors of anthocyanin formation. PMID- 17745681 TI - Forthcoming Events. PMID- 17745682 TI - Optical Rotation and Rotatory Dispersion. PMID- 17745683 TI - POSTPONEMENT OF THE NEW YORK MEETING. PMID- 17745685 TI - INFLUENCE OF THE ENVIRONMENT ON THE EXPRESSION OF HEREDITARY FACTORS IN RELATION TO PLANT BREEDING. PMID- 17745687 TI - THE ST. LOUIS MEETING OF THE AMERICAN SOCIETY OF AGRONOMY. PMID- 17745684 TI - WARTIME CHEMICALS FROM NATURAL GAS. PMID- 17745686 TI - TRANSFER TO THE UNITED STATES OF THE HEADQUARTERS OF THE INTERNATIONAL SOCIETY OF SURGERY. PMID- 17745688 TI - GENETICS IN THE U. S. S. R. PMID- 17745689 TI - THE ENGINEERING COLLEGE RESEARCH ASSOCIATION. PMID- 17745690 TI - THE UPPER PENINSULA MINERAL RESOURCES CONFERENCE. PMID- 17745691 TI - THE OLD STARFISH-CLAM QUESTION. PMID- 17745692 TI - SEGREGATION OF TYPE SPECIMENS. PMID- 17745693 TI - DEFORMATION OF ROCK STRATA BY EXPLOSIONS. PMID- 17745694 TI - THE FIRST FREE-LIVING FRESHWATER JELLYFISH FROM SOUTH AMERICA. PMID- 17745695 TI - THE PITTSBURGH MEETING OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17745696 TI - AN INFECTIOUS AGENT FROM CASES OF ATYPICAL PNEUMONIA APPARENTLY TRANSMISSIBLE TO COTTON RATS. PMID- 17745697 TI - DESTRUCTION OF HYPERTENSIN AND PEPSITENSIN BY AN AMINOPEPTIDASE OBTAINED FROM YEAST. PMID- 17745699 TI - THE PREPARATION OF A SUCRASE-FREE TAKA-MALTASE. PMID- 17745698 TI - THE OCCURRENCE OF INTRAVASCULAR AGGLUTINATIONS IN AVIAN MALARIA. PMID- 17745700 TI - A PLATINUM SCOOP FOR TRANSFERRING STERILE POWDERS. PMID- 17745701 TI - The ames assay. PMID- 17745702 TI - Government talk. PMID- 17745703 TI - Construction of human tumor viruses? PMID- 17745705 TI - Paper mills and campus ethics. PMID- 17745704 TI - The ames assay. PMID- 17745706 TI - Paper mills and campus ethics. PMID- 17745707 TI - Paper mills and campus ethics. PMID- 17745708 TI - Paper mills and campus ethics. PMID- 17745709 TI - Paper mills and campus ethics. PMID- 17745710 TI - Paper mills and campus ethics. PMID- 17745711 TI - Erratum. AB - In the letter "Kepone chronology" by Rudolph J. Jaeger (9 July, p. 94, column 3, paragraph 3, line 9), the airborne Kepone concentration in the Life Science Products plant measured by state of Virginia officials in July 1975 was erroneously given as 3 mg/cm(3). The correct concentration was 3 mg/m(3). A portion of a sentence in the preceding paragraph was also erroneously omitted (line 14). The sentence should have read, "A chronicity factor, calculated from these data, is the ratio of the single LD(50) value divided by the LD(50) value in repeatedly dosed animals." PMID- 17745712 TI - Understanding mathematical proofs: conceptual barriers. PMID- 17745714 TI - Astronomy and cosmology at angkor wat. PMID- 17745713 TI - Glamorous nuclear fusion. PMID- 17745715 TI - Elementary modes of excitation in the nucleus. PMID- 17745716 TI - Prehistoric hawaiian fishponds. AB - One of the important technological concepts that was developed in the Hawaiian Islands is that of the fishpond. From the 14th to the 19th centuries, these sites served as aquariums for the raising of selected fish. From its inception until the 1900's, the fishpond progressed little in design and function. Its rudimentary nature was a function of both technology and religion. Because of the open ditches, sluice grates, and permeable walls, neither the types nor the quantity of juvenile fish entering or leaving could be controlled. In addition, religious beliefs prevented experimenting with fertilization to increase yield. Although seemingly inefficient, the native aquacultural system was not intended to produce a great amount of fish but rather to yield selected fish on call. Fishponds became symbols of the chiefly right to conspicuous consumption and to ownership of the land and its resources. They were manifestations of the chief's political power and his ability to control and tap his resources. As soon as the native aristocracy changed to a Western-style kingdom, the fishpond's function changed, until, by the 1930' s, the majority were simply archeological remains mounds and walls of rock along a river or shore. PMID- 17745717 TI - Grant applications: panel finds new laws enable stealing of ideas. PMID- 17745718 TI - The B-1 and the cruise missile: to have and have not. PMID- 17745719 TI - Nuclear power: france forges ahead on ambitious plan despite critics. PMID- 17745720 TI - Fusion Research (III): New Interest in Fusion-Assisted Breeders. PMID- 17745722 TI - Effects of salinity. PMID- 17745721 TI - Ambiguous commitment. PMID- 17745723 TI - The inner Earth. PMID- 17745724 TI - Ecology of small mammals. PMID- 17745725 TI - Catabolic processes. PMID- 17745727 TI - PRODUCTS and MATERIALS. PMID- 17745728 TI - Bipolarity on the campus. PMID- 17745726 TI - A high-efficiency power cycle in which hydrogen is compressed by absorption in metal hydrides. AB - A high-efficiency power cycle is proposed in which molecular hydrogen gas is used as a working fluid in a regenerative closed Brayton cycle. The hydrogen gas is compressed by an absorption-desorption cycle on metal hydride (FeTiH(x)) beds. Low-temperature solar or geothermal heat (temperature about 100 degrees C) is used for the compression process, and high-temperature fossil fuel or nuclear heat (temperature about 700 degrees C) supplies the expansion work in the turbine. Typically, about 90 percent of the high-temperature heat input is converted to electricity, while about 3 kilowatts of low-temperature heat is required per kilowatt of electrical output. PMID- 17745729 TI - Ion binding by synthetic macrocyclic compounds. AB - The existence of synthetic macrocyclic molecules with hydrophilic cavities containing multiple binding atoms and with hydrophobic exteriors gives rise to extraordinary possibilities with respect to the design and synthesis of molecules with specific cation and anion binding properties. The preparation of many new macrocyclic compounds has recently been reported, but few practical applications for them have been suggested. From the information available, it is becoming clear that it should be possible to synthesize macrocycles that will have specified, or selected, ion binding properties. Cavity size can be varied to accommodate only those cations or anions within a specified narrow band of sizes. Numbers and types of coordinating atoms can be chosen to give essentially electrostatic or covalent bonding or a combination of the two in a metalmacrocycle complex. The metal ligand bond appears to be predominantly ionic in the case of the cyclic polyethers but the covalent character increases on substitution of sulfur or nitrogen for oxygen donor atoms. The essential hydrophobic exteriors of the macrocycles can be modified by the addition of side chains and groups to facilitate the solution of anions and cations in organic solvents. The structures of many macrocycles can be made to approximate naturally occurring molecules, that is, cyclic polyethers similar to macrocyclic antibiotics of the valinomycin and nonactin types and cyclic polyamines similar to porphyrins. Macrocycles are also useful as model compounds for the study of metal interactions with biological systems. The synthetic macrocycles thus represent an intriguing new area of coordination chemistry, the systematic study of which should lead to many interesting and useful chemical applications in the field of metal complexation in solution. PMID- 17745730 TI - Agricultural origins: centers and noncenters. AB - I propose the theory that agriculture originated independently in three different areas and that, in each case, there was a system composed of a center of origin and a noncenter, in which activities of domestication were dispersed over a span of 5,000 to 10,000 kilometers. One system includes a definable Near East center and a noncenter in Africa; another system includes a North Chinese center and a noncenter in Southeast Asia and the South Pacific; the third system includes a Mesoamerican center and a South American noncenter. There are suggestions that, in each case, the center and noncenter interact with each other. Crops did not necessarily originate in centers (in any conventional concept of the term), nor did agriculture necessarily develop in a geographical "center." PMID- 17745731 TI - Equinoxial rites of the national research council. PMID- 17745733 TI - Nixon on science. PMID- 17745732 TI - Britain and the EEC: How Strong Is the Technological Argument? PMID- 17745734 TI - L'Affaire eole. PMID- 17745735 TI - AEC to Referee, Not Promote, Industry. AB - A major turnabout in the attitude of the Atomic Energy Commission toward the nuclear power industry was signaled last week by the ntew AEC chairman James R. Schlesinger. With patrician froideur, Schlesinger informed a mass gathering of the nuclear power industry at Bal Harbour, Florida, that from henceforth the AEC woLuld act as the referee of nuclear power, not its promoter. Saying he would dispense with the "anecdotes and clumsy jests" customary on such occasions, Schlesinger served notice on the nuclear banqueters that their cozy relationship with the AEC was at an end. The industry should not expect the AEC to fight its battles: it should take its own case to the public-as the Sierra Club does. Nor did the AEC intend to bend the rules in industry's favor. "We have had a fair amount of advice on how to evade the clear mandate of the federal courts. It is advice we did not think proper to accept," Schlesinger said. Even on matters of engineering quality, the diners were told they knew full well they had "reason to blush." Roused out of any postprandial euphoria by this glacial disdain, the industry representatives heard the new chairman announce the following radical upheavals in official AEC philosophy. PMID- 17745736 TI - Human environment conference: citizen advisers muddle through. PMID- 17745737 TI - One china or two at stockholm. PMID- 17745738 TI - Nobel prize for economics: kuznets and economic growth. PMID- 17745739 TI - Pauling pickets. PMID- 17745740 TI - Madagascar's Paleoposition: New Data from the Mozambique Channel. AB - The main paleopositions that have been proposed for Madagascar are examined after a recent geological and geophysical survey in the Mozambique Channel. Results from that survey show a north-south ridgelike feature and favor the theory that Madagascar fitted against Somalia rather than against Mozambique to the west. PMID- 17745741 TI - Motions of molecules in liquids: viscosity and diffusivity. AB - The fluidity of a simple liquid is proportional to its degree of expansion over the volume, V(0), at which its molecules are so crowded as to inhibit self diffusion and viscous (as distinguished from plastic) flow. The equation of proportionality is 1/eta = B[(V - V(0))/V(0)] where eta is the viscosity and V is the molal volume. Values of B are the same for normal paraffins from C(3)H(8) to C(7)H(16) and then decrease progressively as the paraffin lengths increase. Values for other liquids, C(6)H(6), CCl(4), P(4), CS(2), CHCl(3), and Hg, appear to vary with repulsive forces. liquids can be moderately fluid when expanded by less than 10 percent; this shows the unreality of some theoretical treatments of the liquid state. Diffusivity begins from the temperature at which V equals V(0) and can be correlated for temperature dependence, and for solute-solvent interrelations. PMID- 17745742 TI - Intercalation complexes of lewis bases and layered sulfides: a large class of new superconductors. AB - Exploration of the generality of the recently discovered reaction whereby certain organic molecules can be inserted between the metallic layers of the superconductors tantalum disulfide and niobium disulfide revealed that a large variety of organic and inorganic molecules can penetrate between the crystalline layers of a number of transition metal dichalcogenides and that the resulting complexes are superconducting if the layered chalcogenide from which they are formed is superconducting. The critical temperatures of the 50 new superconductors we report depend on the nature of the intercalate but are insensitive to a separation of the superconducting planes of up to 57 angstroms. PMID- 17745744 TI - Potassium flux: a common feature of albizzia leaflet movement controlled by phytochrome or endogenous rhythm. AB - Leaflets close when potassium moves into dorsal and out of ventral pulvinule motor cells and open when the flux direction is reversed. This is true whether leaflet movement is controlled by an endogenous rhythm or by phytochrome. PMID- 17745743 TI - Electron microscopy and diffraction of layered, superconducting intercalation complexes. AB - Several layered, transition metal dichalcogenide intercalation complexes with unique superconducting properties have been examined by high-resolution electron microscopy and electron diffraction. Details of the crystalline lattice and of the lattice imperfections have been directly resolved. The results can be correlated with the available x-ray diffraction and chemical data, and they confirm and extend the postulated models. PMID- 17745745 TI - AAAS Symposia. PMID- 17745746 TI - SCIENCE NEWS. PMID- 17745747 TI - CHARLES PROTEUS STEINMETZ AND THE AMERICAN INSTITUTE OF ELECTRICAL ENGINEERS. PMID- 17745749 TI - THE USE OF PERMANENT PAPER IN SCHOLARLY PUBLISHING. PMID- 17745748 TI - OBITUARY. PMID- 17745750 TI - PROFESSIONAL SERVICES VS "LABORATORY INDUSTRY". PMID- 17745751 TI - THE "GUNS" OF SENECA LAKE. PMID- 17745752 TI - CLOCKWISE ROTATION IN PARAMECIUM TRICHIUM. PMID- 17745753 TI - UNUSUAL STROKES OF LIGHTNING. PMID- 17745754 TI - APPARATUS FOR MOTOR CONDITIONING IN CATS. PMID- 17745756 TI - THE DETERMINATION OF MOISTURE IN UNSTABLE PRODUCTS. PMID- 17745755 TI - HEREDITARY VARIATIONS IN THE GESTATION PERIOD OF THE RABBIT. PMID- 17745757 TI - RELATION OF CAROTINOID PIGMENTS TO SEXUAL REPRODUCTION IN PLANTS. PMID- 17745759 TI - FELLOWSHIPS IN THE NATURAL SCIENCES OF THE NATIONAL RESEARCH COUNCIL. PMID- 17745758 TI - PRELIMINARY ANNOUNCEMENT OF THE DURHAM, N. H., MEETING. PMID- 17745760 TI - A READING MACHINE FOR MICROFILMS. PMID- 17745761 TI - A NEW SOCIETY FOR X-RAY AND ELECTRON DIFFRACTION RESEARCH WORKERS. PMID- 17745762 TI - THE AMERICAN ACADEMY OF ARTS AND SCIENCES. PMID- 17745763 TI - MEDAL DAY AT THE FRANKLIN INSTITUTE. PMID- 17745764 TI - THE ANNUAL MEETING OF THE TRUSTEES OF SCIENCE SERVICE. PMID- 17745765 TI - PHYSICS, EXACTING BEYOND ALL COMPROMISE. PMID- 17745766 TI - THE UNIVERSITY OF HAVANA SUMMER SCHOOL. PMID- 17745767 TI - THE CONTINUITY OF THE SCIENTIFIC RECORD. PMID- 17745768 TI - INCOMPLETE FILES OF CURRENT PERIODICALS IN AMERICAN LIBRARIES. PMID- 17745769 TI - PURE AND APPLIED SCIENCE RESEARCH AT MELLON INSTITUTE, 1940-41. PMID- 17745770 TI - AGE SUSCEPTIBILITY OF DUCKS TO THE VIRUS OF THE ROUS SARCOMA AND VARIATION OF THE VIRUS IN THE DUCK. PMID- 17745771 TI - THE DEVELOPMENT OF EARLY MOUSE EMBRYOS IN THE EXTRAEMBRYONIC COELOM OF THE CHICK. PMID- 17745772 TI - INOSITOL AND SPECTACLED EYE IN RATS. PMID- 17745773 TI - AN APPARATUS FOR CONTINUOUS, RAPID AND COMPLETE EXTRACTION OF ESTROGENS. PMID- 17745774 TI - OBTAINING BLOOD FROM MICE. PMID- 17745775 TI - THE AERIAL TRANSMISSION PROBLEMS. PMID- 17745776 TI - THE CALORIMETER AS THE INTERPRETER OF THE LIFE PROCESSES. PMID- 17745777 TI - OBSTACLES TO RESEARCH. PMID- 17745779 TI - A REMARKABLE ECLIPSEZ. PMID- 17745778 TI - DR. CHARLES FREDERICK HOLDER. PMID- 17745780 TI - ON THE DEGREE OF EXACTNESS OF THE GAMMA FUNCTION NECESSARY IN CURVE FITTING. PMID- 17745782 TI - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES. PMID- 17745781 TI - THE ORIGIN OF LOST RIVER AND ITS GIANT POTHOLES. PMID- 17745783 TI - INTERFERENCES WITH TWO GRATINGS. PMID- 17745785 TI - REPORT OF THE GENERAL SECRETARY OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE FOR THE CHICAGO MEETING, CONVOCATION WEEK, 1907-8. PMID- 17745784 TI - THE EFFECT OF X-RAY ON THE RESISTANCE TO CANCER IN MICE. PMID- 17745786 TI - THE INTERDEPENDENCE OF MEDICINE AND OTHER SCIENCES OF NATURE. PMID- 17745788 TI - ALTAMAHA FORMATION OF THE COASTAL PLAIN OF GEORGIA. PMID- 17745787 TI - A BETTER METHOD OF PREPARING HERBARIUM SPECIMENS. PMID- 17745789 TI - THE MEETING OF THE INTERNATIONAL SEISMOLOGICAL ASSOCIATION. PMID- 17745790 TI - CURRENT NOTES ON METEOROLOGY AND CLIMATOLOGY. PMID- 17745791 TI - THE STANLEY EXPEDITION. PMID- 17745792 TI - MEDICAL MUSEUMS. PMID- 17745793 TI - A BIBLIOGRAPHY OF METEOROLOGY. PMID- 17745794 TI - SCIENTIFIC NEWS IN WASHINGTON. PMID- 17745795 TI - The Annual Ring in Trees. PMID- 17745796 TI - Supplementary Reading in Public Schools. PMID- 17745798 TI - HEALTH MATTERS. PMID- 17745797 TI - Temperance-Instruction in the United States. PMID- 17745799 TI - ETHNOLOGY. PMID- 17745800 TI - ELECTRICAL SCIENCE. PMID- 17745801 TI - Answers. PMID- 17745802 TI - Poison-Apparatus of the Mosquito. PMID- 17745803 TI - The Corean Potter's Wheel. PMID- 17745804 TI - HUMAN NATURE IN SCIENCE. PMID- 17745806 TI - THE NATIONAL FOUNDATION FOR INFANTILE PARALYSIS. PMID- 17745805 TI - A. H. REGINALD BULLER. PMID- 17745807 TI - AWARD OF THE PERKIN MEDAL. PMID- 17745808 TI - CHICAGO MEETING OF MATHEMATICIANS. PMID- 17745809 TI - MELLON INSTITUTE TECHNOCHEMICAL LECTURES. PMID- 17745811 TI - THE CHEMICAL TRANSFORMATION OF ESTRONE TO ESTRIOL (THEELOL). PMID- 17745812 TI - CONSTRUCTIVE MEDICINE. PMID- 17745810 TI - ON THE INHIBITION OF UREASE BY PENICILLIN. PMID- 17745814 TI - THE FAILURE OF PURIFIED PENICILLIN TO RETARD THE GROWTH OF GRAFTS OF SARCOMA IN MICE. PMID- 17745813 TI - ON THE EFFECT OF CONTRAST IN MAKING VISUAL STAR COLOR ESTIMATES. PMID- 17745815 TI - SYNTHESIS OF TWO NEW CARBOHYDRATES WITH BACTERIAL PHOSPHORYLASE. PMID- 17745816 TI - ADSORPTION PHENOMENON OF BETACAROTENE. PMID- 17745817 TI - ON THE OCCURRENCE OF A FLUORESCING POLYENE WITH A CHARACTERISTIC SPECTRUM. PMID- 17745818 TI - A 100 KV ELECTRON MICROSCOPE. PMID- 17745819 TI - A WORKING MODEL OF THE HUMAN CIRCULATION. PMID- 17745820 TI - This week in sciece. PMID- 17745821 TI - SOSS: Save Our Social Security. PMID- 17745822 TI - Shelter after earthquakes. PMID- 17745823 TI - Sciencescope. PMID- 17745824 TI - Guarding against internet intruders. PMID- 17745825 TI - Learning to live with a fire wall. PMID- 17745826 TI - Chechnya war threatens science. PMID- 17745827 TI - Is the world warming or not? PMID- 17745828 TI - Walker bill to boost hydrogen sparks democratic grumbling. PMID- 17745829 TI - Painted puzzles line the walls of an ancient cave. PMID- 17745830 TI - For a successful supernova, mix well, then explode. PMID- 17745831 TI - Perils of freezing embryos. PMID- 17745832 TI - Singing the biotech blues. PMID- 17745833 TI - Heavenly eyewear? PMID- 17745834 TI - Another human ancestor steps out. PMID- 17745835 TI - Salk gets crick permanently ... Sort of. PMID- 17745836 TI - Red-hot research papers of 1994. PMID- 17745837 TI - Alternative office gets permanent head. PMID- 17745839 TI - Explosive evolution in tertiary birds and mammals. PMID- 17745838 TI - Industrial-strength protein structures. PMID- 17745840 TI - Ocean Tides for and from TOPEX/POSEIDON. AB - Comparisons of TOPEX/POSEIDON tidal solutions derived from the data of the first year of this altimetric mission with the best previous models and with in situ data show very substantial improvements. Typically, the gain in accuracy for the major lunar tidal component M(2) is 30 percent in root-mean-square differences with reference to a standard ground truth data set from 78 stations distributed over the world ocean. This is a major step, obtained because of the high quality of these altimetric data. The combination of these data with recent numerical models through assimilation methods is pointing toward solutions at the ultimate limits of practical accuracy. PMID- 17745841 TI - Stress-induced Vortex Line Helixing Avalanches in the Plastic Flow of a Smectic A Liquid Crystal. AB - Dynamic surface force measurements of the response of a smectic A to layer normal stress exhibited time dependence for topological events in which single smectic layers were added or removed. Single layer-sized jumps in sample thickness had a rapid component of duration of approximately 1 second that produced most of the change in separation, but that was heralded by a slow precursor acceleration in separation, which began up to a few hundred seconds before. This avalanche-like dynamic signature is consistent with a relaxation mechanism based on the Glaberson-Clem-Bourdon instability of vortex lines (screw dislocations) in the smectic order parameter. PMID- 17745842 TI - Solid-state defect mechanism in vanadyl pyrophosphate catalysts: implications for selective oxidation. AB - High-resolution and in situ electron microscopy of vanadyl pyrophosphate catalysts reacted in alkane (n-butane) and other reducing environments have shown evidence for surface structure modifications accompanied by two sets of symmetry related extended defects. Defect analysis reveals that the defects are formed by pure (glide) shear mechanism. The defect mechanism suggests the presence of basal (coplanar) anion vacancies, associated with Lewis acid centers, at oxygen sites linking corner-sharing phosphorus tetrahedra and vanadyl octahedra in the active plane. These in-plane defect sites may be key to the activation of the alkane, especially in the dehydrogenation. PMID- 17745843 TI - Taboo search: an approach to the multiple minima problem. AB - Described here is a method, based on Glover's taboo search for discrete functions, of solving the multiple minima problem for continuous functions. As demonstrated by model calculations, the algorithm avoids entrapment in local minima and continues the search to give a near-optimal final solution. Unlike other methods of global optimization, this procedure is generally applicable, easy to implement, derivative-free, and conceptually simple. PMID- 17745844 TI - Simulation of recent global temperature trends. AB - Observations show that global average tropospheric temperatures have been rising during the past century, with the most recent portion of record showing a sharp rise since the mid-1970s. This study shows that the most recent portion of the global temperature record (1970 to 1992) can be closely reproduced by atmospheric models forced only with observed ocean surface temperatures. In agreement with a diverse suite of controversial observational evidence from the past 40 years, the upward trend in simulated tropospheric temperatures is caused by an enhancement of the tropical hydrologic cycle driven by increasing tropical ocean temperatures. Although it is possible that the observed behavior is due to natural climate variability, there is disquieting similarity between these model results, observed climate trends in recent decades, and the early expressions of the climatic response to increased atmospheric carbon dioxide in numerical simulations. PMID- 17745845 TI - Climate-related, long-term faunal changes in a california rocky intertidal community. AB - Changes in the invertebrate fauna of a California rocky intertidal community between the period 1931 to 1933 and the period 1993 to 1994 indicate that species' ranges shifted northward, consistent with predictions of change associated with climate warming. Of 45 invertebrate species, the abundances of eight of nine southern species increased and the abundances of five of eight northern species decreased. No trend was evident for cosmopolitan species. Annual mean shoreline ocean temperatures at the site increased by 0.75 degrees C during the past 60 years, and mean summer maximum temperatures from 1983 to 1993 were 2.2 degrees C warmer than for the period 1921 to 1931. PMID- 17745846 TI - Response. PMID- 17745848 TI - Response. PMID- 17745847 TI - Response. PMID- 17745849 TI - Other books of interest. PMID- 17745850 TI - Vignettes: pleasures of chemistry. PMID- 17745852 TI - Products & materials. PMID- 17745851 TI - Gordon research conferences. PMID- 17745854 TI - Society for scientific exploration. PMID- 17745853 TI - Diesel emissions and health. PMID- 17745855 TI - Degrees revoked in soviet union. PMID- 17745856 TI - Erratum. AB - In the report "Long-term synaptic potentiation in the superior cervical ganglion" by T. H. Brown and D. A. McAfee (12 March, p. 1411), equation 2 and the following lines should read: [See equation in the PDF] where [See equation in the PDF] is the early, rapidly decaying component and [See equation in the PDF] is the slowly decaying, long-term component. PMID- 17745857 TI - Leprosy vaccine. PMID- 17745858 TI - The government, secrecy, and university research. PMID- 17745859 TI - Surface spectroscopies with synchrotron radiation. AB - A variety of photoelectron spectroscopies using synchrotron radiation have been devised to study solid surfaces. Measurements of the energies and angular distributions of electrons photoemitted from valence levels yield detailed information on surface electronic states and the chemical bonding of adsorbed atoms and molecules. Core level studies yield surface atom positions and molecular orientations. Some highlights of recent research are presented here. The capabilities of the techniques will be extended by the forthcoming generation of new storage rings dedicated to the production of synchrotron radiation. PMID- 17745860 TI - Conservation and duplication of isozymes in plants. AB - Many enzymes in plants have isozymes because the same catalytic reaction is often present in several subcellular compartments, most frequently the plastids and the cytosol. The number and subcellular locations of the isozymes appear to be highly conserved in plant evolution. However, gene duplication in diploid species and the addition of genomes in polyploid species have increased the number of isozymes. PMID- 17745861 TI - A Doomsday Plan for the 1990's. PMID- 17745863 TI - The first lasers. PMID- 17745862 TI - Gould Advances Inventor's Claim on the Laser. PMID- 17745865 TI - Social insects. PMID- 17745864 TI - Forams. PMID- 17745866 TI - Olmec archeology. PMID- 17745867 TI - Development of germ cells. PMID- 17745868 TI - Pheromone source location by flying moths: a supplementary non-anemotactic mechanism. AB - After the wind was stopped in an insect flight tunnel, male oriental fruit moths continued to fly in zigzag fashion along a stationary pheromone plume. Their lateral excursions from the time-averaged pheromone plume were no greater without wind than in wind of 38 centimeters per second. When the pheromone plume was removed and the wind stopped, males initiated wider track reversals when they reached the pheromone-free area in still air than they had made while in the pheromone plume. This non-anemotactic mechanism of maintaining plume contact possibly a special kind of klinotaxis-when coupled with the orthokinetic retinal velocity of apparent ground pattern motion, allowed males to reach the pheromone source area from 1 to 2 meters away without wind. PMID- 17745869 TI - Rediscovery of the yellow-fronted gardener bowerbird. AB - The long-lost bowerbird Amblyornis flavifrons was found in the Foja Mountains of west New Guinea, and its bower and display were discovered. The bower is a stick tower on a rimmed moss platform, adorned with separate piles of fruit of three different colors. The displaying male extends toward the female a blue fruit set against his golden crest. These observations support a derivation of bower ornamentation from ritual courtship feeding and a transfer of ornamentation from the male's plumage to the bower. PMID- 17745871 TI - PRODUCTS and MATERIALS. PMID- 17745870 TI - Behavioral sequences during dominance hierarchy formation in chickens. AB - Dominance hierarchies near linearity (containing mostly transitive and few intransitive triads) are common in many species. Analysis of the possible sequences for forming dominance relationships shows that two ensure transitivity, and two others produce either transitive or intransitive triads. Experiments with chickens show that in groups of three and four they most often use the two sequences that ensure transitivity and thus linear hierarchies. Examination of such sequences may help explain the formation of near linear hierarchies in other species. PMID- 17745872 TI - GEOPHYSICS AT THE BRUSSELS MEETINGS, JULY 18-28,1919. PMID- 17745873 TI - A MEDICAL SCHOOL, IN THE WAR AND AFTER. PMID- 17745874 TI - UNIFORMITY IN SYMBOLS. PMID- 17745875 TI - DISTRIBUTION OF THE FRESH-WATER MEDUSA, CRASPEDACUSTA, IN THE UNITED STATES. PMID- 17745876 TI - OROGENICS OF THE GREAT BASIN. PMID- 17745877 TI - RESEMBLANCES BETWEEN THE PROPERTIES OF SURFACE FILMS IN PASSIVE METALS AND IN LIVING PROTOPLASM, II. PMID- 17745878 TI - PHILADELPHIA MEETING OF THE AMERICAN CHEMICAL SOCIETY. PMID- 17745880 TI - MEDICAL EDUCATION IN THE UNITED STATES AND CANADA. PMID- 17745879 TI - THE TWENTIETH CENTURY ENGINEER. PMID- 17745881 TI - HENRY AUGUSTUS TORREY. PMID- 17745883 TI - THE ROCKEFELLER INSTITUTE FOR MEDICAL RESEARCH. PMID- 17745882 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17745885 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17745884 TI - THE MUSEUM OF VERTEBRATE ZOOLOGY OF THE UNIVERSITY OF CALIFORNIA. PMID- 17745886 TI - BOTANICAL GARDENS. PMID- 17745888 TI - SCIENCE NEWS. PMID- 17745889 TI - THE DIFFERENTIATION OF SPECIES. PMID- 17745887 TI - CLASSIFICATION OF THE EDENTATES. PMID- 17745891 TI - THE PROMOTION OF KNOWLEDGE OF PRECAMBRIAN LIFE. PMID- 17745890 TI - RESEARCH AND THE TRAINING OF THE RESEARCHER. PMID- 17745892 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17745893 TI - RESEARCH PLUS NEWS-GATHERING. PMID- 17745894 TI - AGRONOMIC JABBERWOCKY. PMID- 17745896 TI - NOTE ON THE INERTIA DYADIC. PMID- 17745895 TI - A NEW AMPHIBIAN RECORD FROM KANSAS, HYLA PHAEROCRYPTA (COPE). PMID- 17745897 TI - DATUM, DATA. PMID- 17745898 TI - GEOLOGIC AGE BY LEAD URANIUM RATIOS. PMID- 17745899 TI - INTELLECTUAL COOPERATION AND BIOLOGY. PMID- 17745900 TI - VARIATION IN SOLAR RADIATION. PMID- 17745901 TI - Wrong Question. PMID- 17745902 TI - Age of Zinjanthropus: The potassium-argon dates recently obtained from Olduvai Gorge, Tanganyika, raise several questions. AB - Because some of the Olduvai Gorge dates are inconsistent, some must be inaccurate; they may all be. Until further tests determine which materials give dependable dates, we do not know which dates are accurate. Until this is learned, the indicated ages must be taken cum grano salis. PMID- 17745904 TI - Congress at Mid-Session: Notes on Communications, Education, and Drug Reform Legislation. PMID- 17745903 TI - Intense Rapid Heating with Flash Discharge Lamps: Heat pulses equivalent to those near atomic blasts may be produced safely with modest apparatus. PMID- 17745905 TI - Fellowship Jungle: NASA Arrives on Graduate Science Scene; Hearings Due on Technical School Bill. PMID- 17745907 TI - Insect Neurosecretory Material Separated by Differential Centrifugation. AB - The factor which accelerates the beating of the insect heart was found to be concentrated in a "large granule" fraction of the corpora cardiaca of the cockroach, Periplaneta americana (L.). PMID- 17745908 TI - Sedimentary Rocks of the Buckeye Range, Horlick Mountains, Antarctica. AB - In the Buckeye Range of the Horlick Mountains, 4000 feet of sedimentary rocks nonconformably overlie a granitic basement and underlie a thick diabasic sill. The sedimentary section consists of Devonian sandstone and shale (Horlick formation), Carboniferous (?) tillite (Buckeye formation), Permian (?) platy and carbonaceous shale (Discovery Ridge formation), and Permian arkose, shale, and numerous coal beds (Mount Glossopteris formation). This apparently is the first report of a Paleozoic tillite in Antarctica. PMID- 17745906 TI - Oceanic Detritus. AB - The quantity and chemical composition of oceanic detritus in the northeastern Pacific Ocean has been measured at different depths from the surface to 3000 meters. The results indicate that oceanic detritus must be considered as a source of food for secondary producers. PMID- 17745909 TI - Intermediates in Biological Nitrogen Fixation. PMID- 17745910 TI - Wave Distortion for Magnetic Moment Effects in Nucleon-Nucleon Scattering. PMID- 17745911 TI - Significance of Dark Reversion of Phytochrome in Flowering of Short-Day Plants. PMID- 17745912 TI - Photosynthetic Phosphorylation at Temperatures Above and Below 0{degrees}C. PMID- 17745913 TI - Fatty Acids in Sedimentary Rocks. PMID- 17745914 TI - Structure of Crystal Surfaces. PMID- 17745915 TI - Neuronal Extension and Glial Supply. PMID- 17745916 TI - Magnetic Resonance Studies of Metal-Enzyme-Substrate Interactions. PMID- 17745917 TI - Localized Fluorometry of Oxidation-Reduction States of Intracellular Pyridine Nucleotide in Brain and Kidney Cortex of the Anesthetized Rat. PMID- 17745919 TI - Observations on the Physiological Thermostat in Homoiotherms. PMID- 17745918 TI - Enzymes of DNA Synthesis in Nuclei of Sea Urchin Embryos. PMID- 17745920 TI - Some Primary Abilities in the Areas of Nonverbal Divergent Production. PMID- 17745921 TI - Neural Discriminations Achieved by Bats in Echolocation. PMID- 17745922 TI - Effects of Chemostimulation of Brain and of Bacterial Endotoxins on Eating and Drinking. PMID- 17745923 TI - Races and Incipient Species in Drosophila paulistorum. PMID- 17745924 TI - Excitatory and Inhibitory Mechanisms in Visceral Pain and Analgesia. PMID- 17745925 TI - High-Pressure Chemistry. PMID- 17745927 TI - Electronic and Steric Factors in Induction of Cancer by Hydrocarbons. PMID- 17745926 TI - The Kinetics of Unimolecular Dissociation. PMID- 17745928 TI - Age of Salt Marsh Peat in Relation to Recent Changes in Sea Level. PMID- 17745929 TI - Galactose Incorporation into Cell-Wall Lipopolysaccharide in Mutant Strain of Salmonella typhimurium. PMID- 17745931 TI - Active Sites of Enzyme Precursors. PMID- 17745930 TI - Metabolism of Inorganic Nitrogen and Its Compounds in Microorganisms. PMID- 17745932 TI - Synthesis of Lactose by Particulate Enzyme Preparations from Guinea Pig and Bovine Mammary Glands. PMID- 17745934 TI - Sensation Measurement by Inverse Judgments. PMID- 17745933 TI - The History of Lake Petenxil, Departamento de El Peten, Guatemala. PMID- 17745935 TI - The Currents in the Ionic Centrifuge. PMID- 17745937 TI - Alterations in Learning Ability Caused by Changes in Cerebral Serotonin or Catechol Amines. PMID- 17745936 TI - A Further Mathematical Aid in Optimizing Engineering Designs. PMID- 17745938 TI - Individuality as Exhibited by Inbred Animals; Its Implications for Human Behavior. PMID- 17745939 TI - The Nerve Fiber as a System in Continuous Flow: Microcinematographic and Electronmicroscopic Demonstrations. PMID- 17745940 TI - Audiogenic Seizures. PMID- 17745941 TI - Geological research. PMID- 17745942 TI - Love canal and legal precedent. PMID- 17745943 TI - Erratum. AB - The title of the letter from Andrew T. Weil (12 Sept., p. 1182) should have been "Coca, not cocaine." The second and third sentences of the second paragraph should have read, "I have advocated research on the therapeutic properties of whole coca leaf. Cocaine and coca are quite different substances with very different potentials for abuse and benefit." PMID- 17745944 TI - Digital readouts on television pictures. PMID- 17745945 TI - Science and engineering. PMID- 17745946 TI - Origin and mechanism of large-scale climatic oscillations. AB - Numerical experiments with a simplified thermodynamic model of the glacier-ocean atmosphere global system have been performed. Characteristic regimes of the system are auto-oscillations with periods varying between 20,000 and 80,000 years. The longer climatic waves are generated by the influence of variations of the earth's orbital parameters. Computed changes of glacial area, temperature, sea level, and other climate characteristics have values within expected ranges. The transition from a relatively warm epoch (when continental ice sheets are absent) to conditions characteristic of the Pleistocene is modeled. The calculated curves show how weak temperature fluctuations have been followed by large-scale oscillations. PMID- 17745947 TI - The cayo santiago primate colony. AB - This is an account of the vicissitudes of the monkeys on Cayo Santiago. In it is described the relationship of the establishment of that primate colony to the development of the National Regional Primate Research Center Program in the United States and the Laboratory of Perinatal Physiology in Puerto Rico. The Cayo Santiago colony opened new aspects of biomedical research and stimulated the general use of nonhuman primates in behavioral as well as physiological investigations. PMID- 17745948 TI - Navy considers scuttling old nuclear subs. PMID- 17745949 TI - NSF Under Challenge from Congress, Engineers. PMID- 17745950 TI - Sawhill is named synfuels chief. PMID- 17745952 TI - Testing for primes gets easier. PMID- 17745951 TI - FDA caffeine decision too early, some say. PMID- 17745953 TI - Plug pulled on chemistry computer center. PMID- 17745955 TI - Chromosome numbers. PMID- 17745954 TI - An "NRCC" for Industrial Chemists? PMID- 17745956 TI - Visual adaptations. PMID- 17745957 TI - Plant physiology. PMID- 17745958 TI - Social judgment processes. PMID- 17745959 TI - Carbynes: carriers of primordial noble gases in meteorites. AB - Five carbynes (triply bonded allotropes of carbon) have been found by electron diffraction in the Allende and Murchison carbonaceous chondrites: carbon VI, VIII, X, XI, and (tentatively) XII. From the isotopic composition of the associated noble-gas components, it appears that the carbynes in Allende (C3V chondrite) are local condensates from the solar nebula, whereas at least two carbynes in Murchison (C2 chondrite) are of exotic, presolar origin. They may be dust grains that condensed in stellar envelopes and trapped isotopically anomalous matter from stellar nucleosynthesis. PMID- 17745960 TI - Carbynes in meteorites: detection, low-temperature origin, and implications for interstellar molecules. AB - Carbon from the Allende meteorite is not graphite but carbyne (triply bonded elemental carbon), inasmuch as on heating to 250 degrees to 330 degrees C it releases mainly triply bonded fragments: -(C identical withC)(n),- with n = 1 to 5, and -(C identical withC)(n)-CN, with n = 1 to 3. Although carbynes have been known to form only by condensation of carbon vapor above 2600 K or by explosive shock of > 600 kilobars, it is found that they also form metastably by the reaction 2CO --> CO(2) + C (solid) at 300 degrees to 400 degrees C in the presence of a chromite catalyst. Such low-temperature formation by surface catalysis may be the dominant source of carbynes on the earth and in meteorites, and a major source of interstellar carbynes and cyanopolyacetylenes. PMID- 17745961 TI - Radioactive Waste Storage Materials: Their agr-Recoil Aging. AB - Ion implantation experiments suggest that the accumulation of alpha-recoil damage in radioactive waste storage materials, which behave like solid-state track detectors, plays a drastic role in their long-term degradation. The understanding of alpha-recoil "aging," overlooked in earlier studies, offers new guidelines for improving waste storage conditions. PMID- 17745962 TI - Long-range atmospheric transport of soil dust from Asia to the tropical north pacific: temporal variability. AB - The concentration of airborne soil dust at Enewetak Atoll(11 degrees N, 162 degrees E) in April 1979 was 2.3 micrograms per cubic meter but decreased steadily to 0.02 microgram per cubic meter over the next 5 months. The spring dust is probably derived from China; its deposition rate ( approximately 0.3 millimeter per 1000 years) suggests that it may be a significant contributor to the deep-sea sediments of the North Pacific. PMID- 17745964 TI - A comparison of thermal observations of mount st. Helens before and during the first week of the initial 1980 eruption. AB - Before and during the first week of the March-April 1980 eruptions of Mount St. Helens, Washington, infrared thermal surveys were conducted to monitor the thermal activity of the volcano. The purpose was to determine if an increase in thermal activity had taken place since an earlier airborne survey in 1966. Nine months before the eruption there was no evidence of an increase in thermal activity. The survey during the first week of the 1980 eruptions indicated that little or no change in thermal activity had taken place up to 4 April. Temperatures of ejected ash and steam were low and never exceeded 15 degrees C directly above the vent. PMID- 17745963 TI - Foraminifera and chlorophyll maximum: vertical distribution, seasonal succession, and paleoceanographic significance. AB - Many planktonic foraminiferal species deposit their shells at the chlorophyll maximum zone, and it is the temperature range here that is relevant to oceanographic models which use ratios of oxygen-18 to oxygen-16 in fossil foraminifera and foraminiferal fossil assemblages to ascertain past climates. During periods of stratification of the upper water column, the temperature at the chlorophyll maximum may differ from the sea surface temperature by 10 degrees C in the western North Atlantic. PMID- 17745965 TI - Oxygen consumption in pelagic marine sediments. AB - Measurements in the interstitial waters of pelagic red clay and carbonate ooze sediments in the central equatorial Pacific show that the dissolved oxygen content decreases with depth and levels off at nonzero values. The supply of reactive organic carbon introduced by bioturbation limits oxygen consumption at depth in the sediment. These gradients should produce diffusive fluxes across the sediment-water interface that average about 8.8 x 10(-14) mole per square centimeter per second or 0.08 milliliter per square meter per hour. PMID- 17745966 TI - Surface charge heterogeneity in amphibole cleavage fragments and asbestos fibers. AB - Aspect ratio and electrophoretic mobility data for amphibole particles reveal that short fibers and blocky cleavage fragments have a smaller net charge than highly elongated particles. Asbestos fibers and cleavage fragments of the same dimensions exhibit the same net negative surface charge but positively charged ends and negatively charged lateral surfaces. PMID- 17745967 TI - Tracing food webs with stable hydrogen isotopes. AB - The hydrogen isotopic content of an animal's food, not water, determines that animal's hydrogen isotopic content. Liver and muscle tissue from mice reared on a diet such that the ratio of deuterium to hydrogen (DIH) of their food and water was kept constant, have the same average D/H ratio as the food source. In a simple, natural population of snails and their possible algal diets, Littorina obtusata (northern Atlantic intertidal snails that feed almost exclusively on the brown alga Fucus vesiculosus) has the same D/H ratio as Fucus vesiculosis and not that of the other algae available to the snails. PMID- 17745968 TI - Juvenile hormone induction of biting behavior in culex mosquitoes. AB - Juvenile hormone deprivation caused by surgical removal of corpora allata shortly after adult emergence blocked the initiation of biting behavior in Culex. pipiens and Culex quinquefasciatus. Reimplantation of corpora allata or injection of a synthetic juvenile hormone (JH-I) corrected the juvenile hormone deficiency and restored biting behavior. Ovariectomy experiments demonstrated that this behavioral effect of juvenile hormone was independent of ovarian involvement. PMID- 17745969 TI - Signals for food: reinforcers or informants? AB - Ring doves pecked one of two keys for food. Pecks at the chosen key then stopped being reinforced, and the signals that normally preceded food were either present or absent. In the presence of signals for food, the dove switched to the second key more quickly. When only one key was used, the same signals acted, as expected, to keep the bird pecking the extinguished key. PMID- 17745970 TI - Protein secretion by the pancreas. PMID- 17745972 TI - Medical education and doctrines. PMID- 17745971 TI - PRODUCTS and MATERIALS. PMID- 17745973 TI - Save the endangered birds! PMID- 17745974 TI - Memories of wisconsin. PMID- 17745975 TI - 94 years of progress? PMID- 17745976 TI - Information exchange groups. PMID- 17745977 TI - Scanning electron microscopes: is high resolution possible? AB - Experiments with this scanning microscope have produced extremely encouraging results so that we feel Confident in predicting high resolution and high contrast after some obvious modifications are made in the system, such as providing a good objective lens. Experience with conventional lenses indicates that the instrument behaves in a predictable manner and there is no reason to doubt that the resolution can be as good as that of a conventional microscope. The use of quadrupole lenses will depend on calculations now being performed. There is cause for optimism; high resolution may also be possible with this kind of lens. Experience with field emission shows that the technology is not difficult and that there is more than enough current available for any conceivable use. Energy loss measurements have been made on a variety of materials. It is attractive to consider the possibility of chemical analysis of selected areas of a specimen. We believe that a very crude form of analysis may indeed be possible. The principal advantage of the use of energy-loss techniques, however, may be in the availability of another contrast mechanism. The ability to "see" small details may be considerably enhanced. Finally, we are experimenting with the possibility of using transmitted electrons of different energy losses to produce different colors on a color television display. This should add an extra element to the picture contrast which may be of some value. PMID- 17745978 TI - Science broadcasting in britain. PMID- 17745979 TI - 1966 nobel laureate in chemistry: robert s. Mulliken. PMID- 17745980 TI - 1966 nobel laureate in physics: alfred kastler. PMID- 17745982 TI - The senate revolt: protesting u.s. Overcommitment abroad. PMID- 17745981 TI - Oceanography: interior department bids for a major role. PMID- 17745983 TI - Nickel-iron spherules from aouelioul glass. AB - Nickel-iron spherules, ranging from less than 0.2 to 50 microns in diameter and containing 1.7 to 9.0 percent Ni by weight, occur in glass associated with the Aouelloul crater. They occur in discrete bands of siliceous glass enriched in dissolved iron. Their discovery is significant tangible evidence that both crater and glass originated from terrestrial impact. PMID- 17745984 TI - Phanerozoic-cryptozoic and related transitions: new evidence. AB - The fossil Pteridinium, a distinctive component of a worldwide early metazoan (Ediacaran)assemblage, is provisionally recorded from probable early Cambrian strata in eastern California. In context with other evidence, this finding implies a Cambrian age for the Ediacaran fauna and approximate coincidence of limits between Phanerozoic-Cryptozoic, Paleozoic-Precambrian, and Cambrian Precambrian. PMID- 17745985 TI - Glaciation about 3,000,000 Years Ago in the Sierra Nevada. AB - Abstract. Major glaciation in the Sierra Nevada of California resulted in the deposition of till which underlies latite 2.7 x 10(6) years old and overlies andesite 3.1 x 10(6) years old. This till, herein called the Deadman Pass till, is the oldest Pleistocene glacial deposit that has been found in temperate latitudes. PMID- 17745986 TI - Nebraskan and kansan stades: complexit and importance. AB - Several Early Pleistocene stadial tills and related soils in Kansas and Nebraska indicate a complex history of ice-sheet fluctuations. It is impossible to assign ages to individual till sheets solely on the basis of position in a stratigraphic column; all Early Pleistocene correlations must be reevaluated. PMID- 17745987 TI - Public Understanding of Science: 133rd AAAS Meeting Washingtone,D.C.26-31 December 1966. PMID- 17745988 TI - Translent free radicals. PMID- 17745989 TI - Forthcoming events. PMID- 17745991 TI - Coming Problems of U.S. Economic Development: A review of two volumes of specially prepared essays by economists, sociologists, and other thinkers. PMID- 17745990 TI - Selecting the Next Generation. PMID- 17745992 TI - News of Science: Development of International Efforts to Avoid Contamination of Extraterrestrial Bodies. PMID- 17745993 TI - On Nucleon-Antinucleon Symmetry in Cosmology. AB - It has been suggested that cosmological models should embody an initial nucleon antinucleon symmetry and that the present ratio of nucleons to antinucleons is the result of a statistical fluctuation. Simple arguments are presented for evolutionary models which appear to rule out this possibility in the development of the universe. PMID- 17745995 TI - Equipment. PMID- 17745996 TI - The President's Manpower Report. PMID- 17745997 TI - The Physics of High-Field Superconductors: New materials, used in lossless magnets at low temperatures, challenge scientific understanding. AB - The recent burst of effort in the area of high-field superconductors has led to the construction of 70,000-oersted coils and the expectation that 100,000-oersted fields will be attained in the near future. The general theory suggests that fields above 300,000 oersteds are conceivable and that current densities of millions of amperes per square centimeter may be attained. Theory and experiment suggest that the upper critical field of materials such as Nb(3)Sn and Nb(.75)Zr(.25) is determined by their tendency to form a mixed state, and that a crucial question concerning their other properties is that of the interaction of this mixed state with imperfections. Lastly, it is possible to make a synthetic high-field superconductor by mechanically subdividing an ideal superconductor. PMID- 17745998 TI - Graduate Aid: Poll of Educators Suggests That Needs Vary Widely in Scientific Disciplines. PMID- 17746000 TI - AEC: Energetic Bargaining Brings Agreement on University Contract Clauses on Security, Information. PMID- 17746001 TI - Space: U.S. and Soviet Scientists Get Along on Detailed Planning for Two Cooperative Projects. PMID- 17745999 TI - R&D: Ill-Starred Nuclear Plane Project Is Subject of Hard Look by General Accounting Office. PMID- 17746002 TI - Geophysics. PMID- 17746003 TI - Floral Induction and the Stimulation of Cell Division in Xanthium. AB - The mitotic index in the apical region of the stem of Xanthium seedlings doubled within the 24 hours immediately following a single inductive dark period and an increase occurred within 16 hours in one case. The significance of this finding in relation to the onset of reproductive development is discussed. PMID- 17746004 TI - Vegetation, Climate, and Coastal Submergence in Connecticut. AB - Pollen analysis of a coastal marsh sediment at Guilford, Connecticut, indicates that there was a period of warmth and dryness preceding 3000 years ago. The subsequent increase of conifers at the expense of oak indicates a reversal that could account for decreasing rates of ice melt and rise of sea level. The record of herbaceous vegetation (grasses vs. sedges) suggests that the rise in the water table has been pulsating in character. PMID- 17746006 TI - Root Hairs, Cuticle, and Pits. AB - The filamentous roots of mustard (Raphanus sativus), radish (Brassica nigra), squash (Cucurbita pepo), and wheat (Triticum aestivum) are covered throughout their length with living nucleated root hairs which may measure 1600 micro or more. The outer walls of piliferous and nonpiliferous cells consist of successive layers of mucilage, cutin, and the cellulose-pectic framework of the cell. Plasmodesmata and pits occur on all cell walls. Under the electron microscope individual pores and pits in the microfibrillar wall are evident throughout the length of the root hair. The "semipermeable membrane" of the root hair zone is thus structurally complex. PMID- 17746005 TI - Superconducting Indium Antimonide. PMID- 17746007 TI - Preliminary Pollen Studies at Lake Zeribar, Zagros Mountains, Southwestern Iran. AB - A late Pleistocene Artemisia steppe, implying a cool, dry climate, changed about 13,000 years ago to an oak-pistachio savanna, as the climate became warmer. About 5500 years ago the savanna thickened to an oak forest, presumably reflecting an increase in precipitation or decrease in temperature to modern levels. PMID- 17746008 TI - Chemical Examination of a Core from Lake Zeribar, Iran. AB - Chemical studies indicate that during the first half of the history of Lake Zeribar, since about 14,800 years ago, the outlet ran very intermittently, thus resulting in a carbonate deposition and a moderate chloride content of the water. The later sediments are largely littoral and cannot easily be interpreted. A fall in exchangeable potassium at the top is probably correlated with the development of extensive beds of aquatic macrophytes. The data appear to be in harmony with those derived from pollen analysis. PMID- 17746009 TI - Crystal Structures of Titanium, Zirconium, and Hafnium at High Pressures. AB - At high pressures, as determined by x-ray analysis, titanium and zirconium metal have a distorted, body-centered-cubic structure. This phase persists on pressure release. The normal hexagonal close-packed structures are recovered when the metals are heated. An electronic shift must occur in the transition. Hafnium metal showed no such transition. PMID- 17746010 TI - Isolated Neuron Preparation for Studies of Metabolic Events at Rest and during Impulse Activity. AB - Application of the Cartesian diver technique to the slowly adapting stretch receptor organ of Crustacea permits quantitative measurements to be made of some metabolic processes in a single intact neuron during different functional states. PMID- 17746011 TI - Ion Exchange at Edge and Interlayer in Montmorillonites Differing in Size. AB - Titrations of hydrogen-saturated montmorillonite with sodium hydroxide indicate that two kinds of hydrogen are exchanged on the surface of the clay. At low pH there is more titratable hydrogen in a fine-size fraction of the clay than there is in a coarse fraction. This indicates neutralization of hydrogen adsorbed at the crystallite edge. The hydrogen adsorbed on the interlayer flake surface is neutralized at a higher pH, and there are more titratable hydrogen ions for the coarse fraction than for the fine. This suggests that surface-charge density is a function of crystallite size, a proposal already made on the basis of other properties of clay. PMID- 17746012 TI - Aeolian Zone. AB - It is postulated that a widespread biotic zone, based on wind-blown organic materials such as pollen and oceanic albuminoids, exists in mountainous and polar regions. The aeolian zone or biome, distinct from alpine and arctic tundra, may be divided into terrestrial, nival, and aquatic divisions. PMID- 17746013 TI - Memory. PMID- 17746014 TI - Letter to the editor. PMID- 17746017 TI - Letter to the editor. PMID- 17746015 TI - Letter to the editor. PMID- 17746016 TI - Letter to the editor. PMID- 17746018 TI - Reply from Argentina. PMID- 17746020 TI - Language pollution. PMID- 17746019 TI - Water vapor in the stratosphere. PMID- 17746021 TI - The national goals research staff report. PMID- 17746022 TI - The principles of conformational analysis. PMID- 17746023 TI - Stanford: why pitzer resigned as president. PMID- 17746025 TI - South Africa: how valid the claim for a uranium process? PMID- 17746024 TI - South Africa affirms development. PMID- 17746026 TI - Paine resigns from space agency. PMID- 17746027 TI - Brain drain: fewer scientists enter u.s., more seek to leave. PMID- 17746028 TI - Kansas: police-student violence imperils university. PMID- 17746029 TI - U.s. Seeks cleaner auto engines. PMID- 17746031 TI - Microwave noise from rainstorms. AB - Observations of microwave noise due to rainstorms have been made at 1415 Mhz. The observed effect may well be due to electrical discharge between water droplets. PMID- 17746030 TI - Gadolinium: Distribution between Aqueous and Silicate Phases. AB - Studies of the partition of trivalent gadolinium between aqueous and silicate phases have been made at temperatures from 800 degrees to 900 degrees C and at pressures from 500 to 1000 bars. Constant values for the distribution coefficients for forsterite, enstatite, and diopside were obtained over a concentration range from 0.6 part per billion to 4 parts per thousand in the solid phases. Ratios of silicate crystal-aqueous phase distribution coefficients to silicate melt-aqueous phase distribution coefficients are close to the values for silicate crystal-silicate melt distribution coefficients estimated from natural systems. The free ion activity of trivalent gadolinium in the silicate melts appears to be less than one-hundredth of its value for aqueous phases of the same concentration. PMID- 17746032 TI - Ice sandwich: functional semipermeable membrane. AB - At a temperature slightly below the freezing point of an aqueous solution, the functions of a nearly perfect semipermeable membrane can be simulated with two nonselective filters with ice sandwiched between them. Potential applications include production of potable water from brackish sources or of highly purified water from tap water. PMID- 17746034 TI - Phenotypic reversion of flacca, a wilty mutant of tomato, by abscisic Acid. AB - The tomato mutant flacca wilts rapidly under water deficit because its stomata resist closure. Application of abscisic acid to intact mutant plants changes their morphology toward the phenotype of the control normal variety, Rheinlands Ruhm. The treated mutant plants do not show wilting symptoms, and the resistance to closure of their stomata decreases with hormone treatment. PMID- 17746033 TI - Polymorphism in benzene, naphthalene, and anthracene at high pressure. AB - Optical observations, in which a microscope was used with the diamond-anvil pressure cell, were carried out on benzene, naphthalene, and anthracene up to temperatures of about 600 degrees C and pressures of approximately 40 kilobars. New high-pressure phases of benzene (benzene III) and anthracene (anthracene II) were observed, and the existence of the high-pressure polymorph, naphthalene II, was verified. All three materials decompose initially to a reddish-orange liquid, and ultimately to amorphous carbon. The decomposition temperatures decrease with increasing molecular size. PMID- 17746036 TI - Releasing the fork. PMID- 17746035 TI - Cooperation with Japan. PMID- 17746038 TI - Education for an age of science. PMID- 17746037 TI - Advanced computing. PMID- 17746040 TI - Weighing the Social Costs of Innovation: A lawsuit against the University of California challenges farm mechanization research and its consequences. PMID- 17746039 TI - Energy problems in latin america. AB - Present energy consumption patterns, known reserves of conventional energy sources (oil, gas, coal, and hydroelectricity), and the impact of the oil crisis on the oil-importing countries of Latin America are discussed. New approaches to energy use, including improvements on end-use efficiency, fuel substitutions, nonconventional energy sources, and changes in consumption patterns, are important. Of particular significance are the alcohol program in Brazil and the possibilities for increased use of hydroelectricity. Investments needed to sustain a reasonable increase in production from conventional energy sources up to 1990 are presented. PMID- 17746041 TI - Tales of the tomato harvester. PMID- 17746042 TI - An ineradicabel disease. PMID- 17746043 TI - Antievolution Rules Are Unconstitutional: The Texas attorney general has said that the state's textbook antievolution rules violate the First Amendment; creationists will fight the opinion. PMID- 17746044 TI - Delaware bay on the rebound. PMID- 17746045 TI - West Germany plans major technology investment. PMID- 17746046 TI - AAAS Annual Meeting New York, 24-29 May 1984: The New York Hilton and the Sheraton Centre. PMID- 17746047 TI - Timekeeping and culture: revolution in time. PMID- 17746048 TI - Influenza Viruses: The origin of Pandemic Influenza Viruses. PMID- 17746049 TI - The neurobiology of vision: parallel processing in the visual system. PMID- 17746050 TI - Contractility: muscle and nonmuscle motility. PMID- 17746051 TI - The frequency of meteorite falls on the Earth. AB - Photographic observations from a network of 60 cameras in western Canada are used to derive the influx rate of meteorites on the earth's surface, the first time instrumental data have been used for this purpose. Forty-three observed events are believed to have dropped between 0.1 and 12 kilograms of meteorites each. The flux values are corrected for a minor latitude effect and agree with earlier estimates near 10 kilograms but vary more slowly with mass. Eight events per year drop at least 1 kilogram of meteorites in an area of 10(6) square kilometers. PMID- 17746052 TI - Fossils of hydrothermal vent worms from cretaceous sulfide ores of the samail ophiolite, oman. AB - Fossil worm tubes of Cretaceous age preserved in the Bayda massive sulfide deposit of the Samail ophiolite, Oman, are apparently the first documented examples of fossils embedded in massive sulfide deposits from the geologic record. The geologic setting of the Bayda deposit and the distinctive mineralogic and textural features of the fossiliferous samples suggest that the Bayda sulfide deposit and fossil fauna are remnants of a Cretaceous sea-floor hydrothermal vent similar to modern hot springs on the East Pacific Rise and the Juan de Fuca Ridge. PMID- 17746053 TI - Control of colonial hydroid macrofouling by free-field ultrasonic radiation. AB - Free-field ultrasonic radiation inhibited the feeding of the macrofouling hydroid Garveia franciscana by causing tentacle contraction at the sonic degasification threshold. Within the frequency range of 250 to 2000 kilohertz, the threshold sound intensity (sonic degasification threshold) that caused tentacle contraction was directly proportional to frequency, with the minimum observed being 0.6 watt per square centimeter at 250 kilohertz. A pulse length of 0.2 second and interpulse period of 102 seconds gave the lowest average power required to produce tentacle contraction at a peak pulse sound intensity of 6.2 watts per square centimeter with a frequency of 250 kilohertz. Twenty-four hour exposures to the sound regime caused destruction of the hydranths and regression of tissue in the stolons. PMID- 17746054 TI - X-ray Laue Diffraction from Protein Crystals. AB - In conventional x-ray diffraction experiments on single crystals, essentially monochromatic x-rays are used. If polychromatic x-rays derived from a synchrotron radiation spectrum are used, they generate a Laue diffraction pattern. Laue patterns from single crystals of macromolecules can be obtained in less-than 1 second, and significant radiation damage does not occur over the course of an exposure. Integrated intensities are obtained without rotation of the crystal, and individual structure factors may be extracted for most reflections. The Laue technique thus offers advantages for the recording of diffraction patterns from short-lived structural intermediates; that is, for time-resolved crystallography. PMID- 17746055 TI - Circadian changes in enzyme concentration account for rhythm of enzyme activity in gonyaulax. AB - A circadian rhythm in the activity of luciferase is partly responsible for rhythmic bioluminescence in the dinoflagellate alga Gonyaulax polyedra. The cyclic activity of this enzyme can be attributed to a corresponding rhythm in the concentration of immunologically reactive luciferase protein. Hence protein turnover (synthesis or degradation or both) is used by the endogenous clock to control the daily rhythm of bioluminescence. PMID- 17746057 TI - Quantitative Biology. PMID- 17746056 TI - Arginine decarboxylase and polyamines required for embryogenesis in the wild carrot. AB - Embryogenic cultures of Daucus carota treated with 1 millimolar alpha difluoromethylarginine, a specific inhibitor of arginine decarboxylase, exhibited nearly a 50 percent reduction in embryo formation compared with controls. Putrescine and spermidine concentrations in the treated cells were greatly reduced. Addition of putrescine, spermidine, or spermine to the culture medium restored embryogenesis in the treated cultures. Embryogenesis was not significantly affected by alpha-difluoromethylornithine, an inhibitor of ornithine decarboxylase. These results suggest that polyamines have a major function in plant embryo development and that the wild carrot synthesizes polyamines through the biosynthetic pathway involving arginine decarboxylase rather than ornithine decarboxylase. PMID- 17746059 TI - Meetinigs & Conferences. PMID- 17746058 TI - Publications Received. PMID- 17746060 TI - This Week inScience. PMID- 17746062 TI - The tasaday debate. PMID- 17746063 TI - Racemization dating: great expectations. PMID- 17746061 TI - SSC Magnet Development. PMID- 17746065 TI - Puzzling out the tectonic plates. PMID- 17746064 TI - New lightest aerogel is nothing to look at. PMID- 17746066 TI - Perils of moderation. PMID- 17746067 TI - Testing relativity. PMID- 17746068 TI - The NSF and Biodiversity. PMID- 17746069 TI - China curbs outflow of students. PMID- 17746071 TI - Primate use down. PMID- 17746072 TI - Alps threatened with deforestation. PMID- 17746070 TI - OTA Speaks Out on Communications. PMID- 17746073 TI - Biotech protection. PMID- 17746074 TI - British brain drain. PMID- 17746075 TI - Poles plug in. PMID- 17746076 TI - "Dead quasars" in nearby galaxies? AB - The nuclei of some galaxies undergo violent activity, quasars being the most extreme instances of this phenomenon. Such activity is probably short-lived compared to galactic lifetimes, and was most prevalent when the universe was only about one-fifth of its present age. A massive black hole seems the inevitable end point of such activity, and dead quasars should greatly outnumber active ones. In recent years, studies of stellar motions in the cores of several nearby galaxies indicate the presence of central dark masses which could be black holes. This article discusses how such evidence might be corroborated, and the potential implications for our understanding of active galaxies and black holes. PMID- 17746077 TI - Painting the phase space portrait of an integrable dynamical system. AB - For an integrable dynamical system with one degree of freedom, "painting" the integral over the phase space proves to be very effective for uncovering the global flow down to minute details. Applied to the main problem in artificial satellite theory, for instance, the technique reveals an intricate configuration of equilibria and bifurcations when the polar component of the angular momentum approaches zero. PMID- 17746079 TI - Evidence for band overlap metallization of hydrogen. PMID- 17746080 TI - Clostridia. Nigel P. Minton and David J. Clarke, Eds. Plenum, New York, 1989. xiv, 304 pp., illus. $49.50. Biotechnology Handbooks, vol. 3. PMID- 17746078 TI - In reply: evidence for band overlap metallization of hydrogen. PMID- 17746081 TI - Productivity of the Ocean. Present and Past. W. H. Berger, V. S. Smetacek, and G. Wefer, Eds. Wiley-Interscience, New York, 1989. xviii, 470 pp., illus. $146. Life Sciences Research Reports, vol. 44. From a workshop, Berlin, F.R.G., April 1988. PMID- 17746082 TI - The Biology of Euglena. Vol. 4, Subcellular Biochemistry and Molecular Biology. Dennis E. Buetow, Ed. Academic Press, San Diego, CA, 1989. xvi, 528 pp., illus. $150. PMID- 17746083 TI - Quaternary Type Sections. Imagination or Reality? Jim Rose and Christian Schluchter, Eds. Balkema, Brookfield, VT, 1989. viii, 208 pp., illus. $48. From a symposium, Zurich, Switzerland, Oct. 1985. PMID- 17746084 TI - Products & materials. PMID- 17746085 TI - CONSERVATION OF MINERALS. PMID- 17746086 TI - GRANTS IN SUPPORT OF RESEARCH ON THE BIOLOGICAL EFFECTS OF RADIATION. PMID- 17746087 TI - MORE THAN TWO PRE-CAMBRIAN GRANITES IN THE CANADIAN SHIELD. PMID- 17746088 TI - A WIDE-SPREAD ERROR RELATING TO THE PYTHAGOREANS. PMID- 17746089 TI - TRANSFORMATION OF COORDINATION AFTER CROSSING THE ACHILLES TENDONS IN THE FROG. PMID- 17746090 TI - WELL RECORDS SOUGHT. PMID- 17746092 TI - THE PRESENCE IN SELF-BLANCHING CELERY OF UNSATURATED COMPOUNDS WITH PHYSIOLOGICAL ACTION SIMILAR TO ETHYLENE. PMID- 17746091 TI - CHEMICAL RELATIONSHIPS BETWEEN COMPOUNDS OF PHYSIOLOGICAL IMPORTANCE HAVING THE PHENANTHRENE NUCLEUS. PMID- 17746093 TI - THE FORMATION OF CARBOHYDRATE FROM GLYCEROPHOSPHATE IN THE LIVER OF THE RAT. PMID- 17746094 TI - NEW CANCER-PRODUCING HYDROCARBONS. PMID- 17746095 TI - BACTERIOLOGICAL EXAMINATION OF THE CONTENTS OF THE CLOSED ARM IN THE SMITH FERMENTATION TUBE. PMID- 17746096 TI - A DEVICE FOR AERATING AND CIRCULATING AQUARIUM WATER. PMID- 17746097 TI - This week in science. PMID- 17746098 TI - Policies for science and technology. PMID- 17746099 TI - Support for the SSC. PMID- 17746100 TI - DOE, Taiwan, and SSC Support. PMID- 17746101 TI - Sciencescope. PMID- 17746102 TI - A series of overlapping studies. PMID- 17746103 TI - National academy elects new members. PMID- 17746104 TI - Dispute over exxon valdez cleanup data gets messy. PMID- 17746106 TI - Finally, a hotter superconductor. PMID- 17746105 TI - Designer solids: haute couture in chemistry. PMID- 17746107 TI - A double dose of gamma-ray bursts. PMID- 17746108 TI - Late triassic extinctions and the origin of the dinosaurs. PMID- 17746109 TI - Rheology of the upper mantle: a synthesis. AB - Rheological properties of the upper mantle of the Earth play an important role in the dynamics of the lithosphere and asthenosphere. However, such fundamental issues as the dominant mechanisms of flow have not been well resolved. A synthesis of laboratory studies and geophysical and geological observations shows that transitions between diffusion and dislocation creep likely occur in the Earth's upper mantle. The hot and shallow upper mantle flows by dislocation creep, whereas cold and shallow or deep upper mantle may flow by diffusion creep. When the stress increases, grain size is reduced and the upper mantle near the transition between these two regimes is weakened. Consequently, deformation is localized and the upper mantle is decoupled mechanically near these depths. PMID- 17746111 TI - A photomicrodynamic system with a mechanical resonator monolithically integrated with laser diodes on gallium arsenide. AB - A cantilever resonant microbeam, laser diodes, and a photodiode have been fabricated on the surface of a gallium arsenide substrate. The microbeam is excited photothermally by light from a laser diode. The vibration is detected with a photodiode as the variation in light output caused by the difference in optical length between the microbeam and another laser diode. A high carrier-to noise ratio (45 decibels) is achieved with a short (3 micrometers) external cavity length. Such a small distance allows a lensless system, which increases the ease of fabrication. This work could lead to applications in which photomicrodynamic systems are monolithically integrated on a gallium arsenide substrate with surface micromachining technology. PMID- 17746110 TI - Annealing c60+: synthesis of fullerenes and large carbon rings. AB - Laser vaporization of graphite generates C(60)(+) cluster ions that are fullerenes and a mixture of roughly planar polycyclic polyyne ring isomers. Experimental studies of the annealing of the non-fullerene C(60)(+) ions indicate that they can be converted (in the gas phase) into the fullerene and an isomer that appears to be a large monocyclic ring. Some fragmentation is associated with conversion to the fullerene geometry, but the majority of the non-fullerene C(60)(+) isomers are cleanly converted into an intact fullerene. The emergence of the monocyclic ring (as the clusters are annealed) suggests that this is a relatively stable non-spheroidal form of these all carbon molecules. The estimated activation energies for the observed structural interconversions are relatively low, suggesting that these processes may play an important role in the synthesis of spheroidal fullerenes. PMID- 17746112 TI - X-ray Tomographic Study of Chemical Vapor Infiltration Processing of Ceramic Composites. AB - The fabrication of improved ceramic-matrix composites will require a better understanding of processing variables and how they control the development of the composite microstructure. Noninvasive, high-resolution methods of x-ray tomography have been used to measure the growth of silicon carbide in a woven Nicalon-fiber composite during chemical vapor infiltration. The high spatial resolution allows one to measure the densification within individual fiber tows and to follow the closure of macroscopic pores in situ. The experiments provide a direct test of a recently proposed model that describes how the surface area available for matrix deposition changes during infiltration. The measurements indicate that this surface area is independent of the fiber architecture and location within the preform and is dominated by large-scale macroporosity during the final stages of composite consolidation. The measured surface areas are in good agreement with the theoretical model. PMID- 17746114 TI - Copernicus: a regional probe of the lunar interior. AB - Earth-based telescopic spectral imaging techniques were used to document the spatial distribution of crater materials within the large lunar crater Copernicus at the subkilometer scale on the basis of spectral ultraviolet-visible-near infrared characteristics. The proposed spectral mixing analysis leads to a first order mapping of the impact melt material within the crater. Olivine was detected not only within the three central peaks but also along a significant portion of the crater rim. Consideration of an olivine-bearing end-member in the mixing model emphasizes the overall morphological pattern of the rim and wall terraces in the associated fraction image. The identification of widely exposed olivine units supports the idea that the lower crust and possibly the lunar mantle itself are regionally at shallow depth. PMID- 17746113 TI - The Ischigualasto Tetrapod Assemblage (Late Triassic, Argentina) and 40Ar/39Ar Dating of Dinosaur Origins. AB - (40)Ar/(39)Ar dating of sanidine from a bentonite interbedded in the Ischigualasto Formation of northwestern Argentina yielded a plateau age of 227.8 +/- 0.3 million years ago. This middle Carnian age is a direct calibration of the Ischigualasto tetrapod assemblage, which includes some of the best known early dinosaurs. This age shifts last appearances of Ischigualasto taxa back into the middle Carnian, diminishing the magnitude of the proposed late Carnian tetrapod extinction event. By 228 million years ago, the major dinosaurian lineages were established, and theropods were already important constituents of the carnivorous tetrapod guild in the Ischigualasto-Villa Union Basin. Dinosaurs as a whole remained minor components of tetrapod faunas for at least another 10 million years. PMID- 17746116 TI - Star wars in context. PMID- 17746117 TI - Andean imperialism. PMID- 17746115 TI - Postglacial offset along the Seattle fault. PMID- 17746118 TI - A disease in resurgence. PMID- 17746119 TI - Vignettes: second thoughts. PMID- 17746120 TI - Mechanisms of learning. PMID- 17746121 TI - Products & materials. PMID- 17746123 TI - DAVID EUGENE SMITH. PMID- 17746125 TI - AWARDS OF THE AMERICAN CHEMICAL SOCIETY. PMID- 17746122 TI - NEW METHODS IN THE STUDY OF STELLAR SPECTRA. PMID- 17746124 TI - VITAL STATISTICS OF ENGLAND AND WALES. PMID- 17746126 TI - AWARDS SPONSORED BY THE AMERICAN INSTITUTE OF NUTRITION. PMID- 17746127 TI - THE FOURTH SCIENCE TALENT SEARCH. PMID- 17746128 TI - THE AMERICAN CHEMICAL SOCIETY AND THE UNIVERSAL OIL PRODUCTS COMPANY. PMID- 17746129 TI - THE OBLIGATIONS OF A SCIENTIST. PMID- 17746130 TI - BIOLOGICAL TERMINOLOGY. PMID- 17746131 TI - THE POSSIBLE ROLE OF CHARA FRAGILIS IN MOSQUITO CONTROL. PMID- 17746133 TI - ALKALINE PHOSPHATASE IN THE OVARIAN FOLLICLES AND CORPORA LUTEA. PMID- 17746134 TI - ABSENCE OF GLUCOSE EFFECT ON GASTRO-INTESTINAL PHOSPHATE ABSORPTION. PMID- 17746132 TI - THE EFFECT OF COCARBOXYLASE ON THE CONVERSION OF FAT TO CARBOHYDRATE. PMID- 17746135 TI - ANTIGENIC DIFFERENCES BETWEEN THE SPERM OF DIFFERENT INBRED STRAINS OF MICE. PMID- 17746136 TI - A CLOSED CELL FOR ELECTRON MICROSCOPY. PMID- 17746137 TI - A METHOD FOR CENTRIFUGING AT LOW TEMPERATURE. PMID- 17746138 TI - Suggestions for Contributors. PMID- 17746139 TI - Meetings & Conferences. PMID- 17746140 TI - The Work of Richard von Mises: 1883-1953. PMID- 17746141 TI - A Golden Anniversary. PMID- 17746142 TI - Miscellaneous Publications. PMID- 17746143 TI - Retardation of Maturation in Magnolia Flowers by Maleic Hydrazide. PMID- 17746145 TI - Preliminary Studies on the Structure of Angiotonin. PMID- 17746144 TI - The Use of Electrically Conducting Glass for Counting Lesions. PMID- 17746147 TI - Geochronological Significance of Extinct Natural Radioactivity. PMID- 17746146 TI - The Spectrum of Magnesium in Concentrated Sulfuric Acid. PMID- 17746148 TI - On Scientific Writing. PMID- 17746149 TI - SCIENTIFIC RESEARCH IN RELATION TO AGRICULTURAL PROBLEMS. PMID- 17746150 TI - LIMITATIONS OF EXPERIMENT IN EXPLAINING NATURAL HABIT, AS ILLUSTRATED BY THE DIURNAL MIGRATION. PMID- 17746151 TI - ELECTRICITY AND GRAVITATION. PMID- 17746152 TI - CONCERNING DIASTROPHISM. PMID- 17746153 TI - PROTOZOA IN SAWDUST FOR CLASS WORK. PMID- 17746155 TI - THE AMERICAN CHEMICAL SOCIETY. IX. PMID- 17746154 TI - THE INFLUENCE OF DRY VERSUS FRESH GREEN PLANT TISSUE ON CALCIUM ASSIMILATION. PMID- 17746156 TI - PRESENT-DAY CONDITIONS AND THE RESPONSIBILITIES OF THE UNIVERSITY. PMID- 17746157 TI - THE CHEMIST AND THE COMMUNITY. PMID- 17746158 TI - ANTHROPOLOGY AT THE NEW YORK MEETING. PMID- 17746159 TI - THE DISPUTED ERUPTIONS OF VESUVIUS. PMID- 17746162 TI - CURRENT NOTES ON METEOROLOGY AND CLIMATOLOGY. PMID- 17746161 TI - A PLANT-TUMOR OF BACTERIAL ORIGIN. PMID- 17746160 TI - THE MISLEADING AND THE NON-INFORMING TITLE. PMID- 17746163 TI - EXPERIMENTS ON HUMAN NUTRITION. PMID- 17746164 TI - COMMEMORATION OF THE TWO HUNDREDTH ANNIVERSARY OF THE BIRTH OF LINNAeUS. PMID- 17746165 TI - The Fetish of Experiment. PMID- 17746167 TI - Postglacial Hypsithermal Interval. PMID- 17746166 TI - Science and Public Understanding. PMID- 17746169 TI - Critical Preparation of Plant Material for Autoradiography. PMID- 17746168 TI - News of Science. PMID- 17746171 TI - Meetings and Societies. PMID- 17746170 TI - Carbon-14 Tetrachloride Produced by Neutron Irradiation of Aniline-and Pyridine CCl4 Solutions. PMID- 17746172 TI - EQUIPMENT NEWS. PMID- 17746173 TI - Errattm. AB - In the letter from George R. Hendrey (7 Oct.. p. 8). the references in the headings of tables 1 and 2 were incorrect. They should have been given as (1) and (2). respectively. PMID- 17746175 TI - Solution of math problem. PMID- 17746176 TI - The journal glut. PMID- 17746177 TI - Quality: the competitive strategy. PMID- 17746178 TI - Three Mars years: viking lander 1 imaging observations. AB - The Mutch Memorial Station (Viking Lander 1) on Mars acquired imaging and meteorological data over a period of 2245 martian days (3:3 martian years). This article discusses the deposition and erosion of thin deposits (ten to hundreds of micrometers) of bright red dust associated with global dust storms, and the removal of centimeter amounts of material in selected areas during a dust storm late in the third winter. Atmospheric pressure data acquired during the period of intense erosion imply that baroclinic disturbances and strong diurnal solar tidal heating combined to produce strong winds. Erosion occurred principally in areas where soil cohesion was reduced by earlier surface sampler activities. Except for redistribution of thin layers of materials, the surface appears to be remarkably stable, perhaps because of cohesion of the undisturbed surface material. PMID- 17746180 TI - New security measures denounced. PMID- 17746179 TI - Phaseolin gene from bean is expressed after transfer to sunflower via tumor inducing plasmid vectors. AB - Sequences coding for the bean seed protein phaseolin were inserted into transferred DNA regions of tumor-inducing plasmids. Constructions were devised in which the coding region of phaseolin was fused in the correct reading frame with the coding region of octopine synthase and placed under the transcriptional control of the octopine synthase promoter. Other plasmids were prepared to permit expression of the phaseolin-encoding sequences from the flanking phaseolin promoter region. The RNA transcribed in sunflower cells transformed with these constructions was characterized by hybridization procedures, SI nuclease mapping, and by translation in vitro of extracted RNA. These tests showed that the genomic intervening sequences were correctly excised. Immunoreactive phaseolin polypeptides were detected by enzyme-linked immunosorbent assay and by antibody hybridization to electrophoretically separated protein extracts of sunflower tissues isolated from crown gall tumors and of transformed sunflower cells grown in tissue culture. These results demonstrate the expression of a plant gene after transfer to a taxonomically distinct botanical family. PMID- 17746181 TI - DOE Officially Terminates ISABELLE. PMID- 17746182 TI - Creationists, ACLU to Do Battle Again. PMID- 17746183 TI - Federal Court Finds IBT Officials Guilty of Fraud. PMID- 17746185 TI - The pros and cons of the research-teaching link. PMID- 17746184 TI - House Committee Votes to Delay ASAT Deployment. PMID- 17746186 TI - Insider Nominated for Disputed ACDA Post. PMID- 17746187 TI - Delay spells trouble for spacelab. PMID- 17746188 TI - Entrepreneurs implicated in espionage. PMID- 17746189 TI - Carbon Dioxide and a Changing Climate: A National Research Council view of the carbon dioxide greenhouse includes inevitable climatic warming but no certain disasters. PMID- 17746190 TI - IBM Drops Superconducting Computer Project: Problems with a high-speed memory chip would delay a Josephson junction computer long enough for semiconductors to catch up. PMID- 17746191 TI - Science communication course directory published. PMID- 17746193 TI - Obituaries. PMID- 17746194 TI - Galapagos evolution described. PMID- 17746192 TI - CSFR Begins Project on Secrecy and Openness in Technical Communication. PMID- 17746195 TI - List of Women's Groups to Be Revised. PMID- 17746196 TI - AAAS/CAST Symposium Focuses on Ruminants. PMID- 17746197 TI - Toward a unitary theory of mind: the architecture of cognition. PMID- 17746198 TI - Plant structures: xylem structure and the ascent of sap. PMID- 17746199 TI - Microbial habitats: microbes in their natural environments. PMID- 17746200 TI - Planetary science: physics of the jovian magnetosphere. PMID- 17746201 TI - Sequential Basal faults in devonian dolomite, nopah range, death valley area, california. AB - Dolomite crystals from the Lost Burro Formation (Devonian) in the Nopah Range, eastern California, display basal stacking disorder as evidenced by transmission electron microscopy. Satellites in electron diffraction patterns indicate that stacking of anions and cations is different from that in ideal dolomite. This example conforms to the model of basal defects proposed by Goldsmith and Graf in 1958 to explain nonstoichiometry in dolomite. This dolomite from the Nopah Range was formed by deep burial replacement of micritic limestone, and its peculiar superstructure is tentatively attributed to the late diagenetic conditions during replacement. PMID- 17746202 TI - Satellite detection of effects due to increased atmospheric carbon dioxide. AB - The use of satellites to detect climatic changes due to increased carbon dioxide was investigated. This method has several advantages over ground-based methods of monitoring climatic change. Calculations indicate that, by monitoring the outgoing longwave flux for small intervals in the 15-micrometer spectral region, changes in stratospheric temperatures due to doubled atmospheric carbon dioxide are large enough to be detected above the various sources of noise. This method can be extended to other spectral regions so that causal links between changes in outgoing longwave radiation due to other trace gases and the thermal structure of the atmosphere could be established. PMID- 17746203 TI - Determining the solar wind speed above active regions using remote radio-wave observations. AB - A new technique has made it possible to measure the velocity of portions of the solar wind during its flow outward from the sun. This analysis utilizes spacecraft (ISEE-3) observations of radio emission generated in regions of the solar wind associated with solar active regions. By tracking the source of these radio waves over periods of days, it is possible to measure the motion of the emission regions. Evidence of solar wind acceleration during this outward flow, consistent with theoretical models, has also been obtained. PMID- 17746206 TI - INDIAN RELICS IN SOUTH JERSEY. PMID- 17746207 TI - NOTES ON SOME MINNESOTA MOUNDS. PMID- 17746205 TI - Electrical brain stimulation and the localization of cardiopulmonary function. PMID- 17746204 TI - Predatory capture of toads by fly larvae. AB - A natural occurrence of predation upon toads (Scaphiopus multiplicatus) by fly larvae (Tabanus punctifer) is described. The larvae lie buried in mud, seize the toads with hooked mandibles, pull them partly into the mud, and kill them by feeding on their body fluids. The larvae may ordinarily subsist mostly on invertebrates and take Amphibia only opportunistically. PMID- 17746209 TI - THE WORLD'S CONGRESS AUXILIARY OF THE COLUMBIAN EXPOSITION. PMID- 17746208 TI - CURRENT NOTES ON CHEMISTRY.--II. PMID- 17746210 TI - A NEW FACTOR IN FRUIT GROWING. PMID- 17746212 TI - ALTITUDE IN SPITE OF HUMIDITY AS A CURE OF BERI-BERL*. PMID- 17746211 TI - RAILROAD SIGNALING. PMID- 17746213 TI - ON THE EXTREMES OF HEAT AND COLD UNDER WHICH THE LIFE OF SPECIES IS POSSIBLE. PMID- 17746215 TI - PROTECTIVE MIMICRY OF A MOTH. PMID- 17746218 TI - COYOTE OR BEAR? PMID- 17746219 TI - EXPLOSIVE GAS IN LOCOMOTIVE EN GINES. PMID- 17746214 TI - THE ORIGIN OF GOLD. PMID- 17746217 TI - ANIMAL VOCABULARIES. PMID- 17746216 TI - THE CIRCULATION IN FRESH-WATER MUSSELS. PMID- 17746220 TI - Shall Biologists Set Up a National Institute? PMID- 17746221 TI - Research in Fundamental Biology and in Agriculture. PMID- 17746223 TI - COMMENTS by Readers. PMID- 17746222 TI - Possible Advantages of Cooperation Between Societies in Publication. PMID- 17746224 TI - Radiocarbon From Cosmic Radiation. PMID- 17746225 TI - A Growth Inhibitor and a Growth Promotor in Sugar Cane. PMID- 17746227 TI - Comparative Nutritive Value of Casein and Lactalbumin for Man. PMID- 17746226 TI - Fowl Spirochetosis Transmitted by Argas persicus (Oken), 1818 From Texas. PMID- 17746228 TI - Simple Syringe Burette. PMID- 17746230 TI - Improved Technique for Enumeration of Escherichia coli on Black Walnut Meats. PMID- 17746231 TI - Laboratory Test of Aviator's Ejection Seat. PMID- 17746229 TI - Cultivation of Microorganisms With the Aid of Cellophane Membranes. PMID- 17746232 TI - Scientifc Book Register. PMID- 17746233 TI - Alternative to peer review? PMID- 17746234 TI - Alternative to peer review? PMID- 17746235 TI - Alternative to peer review? PMID- 17746236 TI - Alternative to peer review? PMID- 17746237 TI - Alternative to peer review? PMID- 17746238 TI - Alternative to peer review? PMID- 17746239 TI - Alternative to peer review? PMID- 17746240 TI - Alternative to peer review? PMID- 17746242 TI - Bridge design. PMID- 17746243 TI - Coal research. PMID- 17746241 TI - Alternative to peer review? PMID- 17746244 TI - Critical data for critical needs. AB - Various types of scientific and technical data are required for the solution of key societal problems such as energy supply, environmental quality, and industrial productivity. Ensuring the quality of these data bases is essential. Modern computer and telecommunications technology offers opportunities for major improvements in the dissemination of data, but data management must be given a higher priority by the scientific community, industry, and government. PMID- 17746247 TI - A hot spot found, another discarded. PMID- 17746245 TI - Allocating petroleum products during oil supply disruptions. AB - Four options for allocating a long-term, severe shortfall of petroleum imports are analyzed: oil price and allocation controls, coupon gasoline rationing, variable gasoline tax and rebate, and no oil price controls with partial rebates. Each of these options is evaluated in terms of four criteria: microeconomic effects, macroeconomic effects, equity, and practical problems. The implications of this analysis for energy contingency planning are discussed. PMID- 17746246 TI - A Manhattan project postscript. PMID- 17746248 TI - Nonmarine iridium anomaly linked to extinctions. PMID- 17746249 TI - Are ocean islands recycled ocean crust? PMID- 17746250 TI - Let us now praise famous boojums. PMID- 17746251 TI - Soviet science and its constraints. PMID- 17746253 TI - A behavioral commonality. PMID- 17746252 TI - Communities in decline. PMID- 17746254 TI - Plant biophysics. PMID- 17746255 TI - The mount st. Helens volcanic eruption of 18 may 1980: minimal climatic effect. AB - An energy-balance numerical climate model was used to simulate the effects of the Mount St. Helens volcanic eruption of 18 May 1980. The resulting surface temperature depression is a maximum of 0.1 degrees C in the winter in the polar region, but is an order of magnitude smaller than the observed natural variability from other effects and will therefore be undetectable. PMID- 17746256 TI - Microwave radiometric measurements of sea surface temperature from the seasat satellite: first results. AB - Initial results from the Seasat scanning multichannel microwave radiometer indicate that the sea surface temperature can be measured with a root-mean-square sensitivity of 1.2 degrees C or better. The first microwave map of sea surface temperature for the entire Pacific has been produced. PMID- 17746259 TI - 1979J3: Discovery of a Previously Unknown Satellite of Jupiter. AB - During a detailed search of Voyager 1 frames for additional observations of the satellite 1979J1, two small dark spots were observed in transit in several consecutive wide-angle frames of the Jovian atmosphere. The size, spacing, and motion of these pairs of dark spots indicated that they were the images of 1979J1 and its shadow. Subsequent analysis of images spanning 6 days, however, proved that the satellite observed in these Voyager 1 frames would have been occulted by Jupiter at the times of the Voyager 2 images of 1979J1 and was, therefore, a new satellite. It was subsequently found in transit on Voyager 2 images within 13 degrees of the Voyager 1 prediction. Its period is 7 hours 4 minutes 30 seconds +/- 3 seconds, and its mean distance is 1.793 Jupiter radii (Jupiter radius = 71,400 kilometers). The observable profile appears to be roughly circular with a diameter of 40 kilometers, and the albedo is approximately 0.05, similar to Amalthea's. PMID- 17746258 TI - Soil as a sink for atmospheric carbon monoxide. AB - The rate of carbon monoxide oxidation by soil increased with increasing carbon monoxide concentration in the gas phase, in line with Michaelis-Menten kinetics. Rates of carbon monoxide oxidation were determined for 20 soils at 0 degrees , 10 degrees , 20 degrees , and 30 degrees C. The observed oxidation rates were used to calculate a global soil uptake rate of atmospheric carbon monoxide of 4.1 x 10(14) grams per year, which is slightly less than the amount of carbon monoxide believed to be produced annually as a result of fossil fuel combustion. PMID- 17746257 TI - Hydrovolcanic explosions: the systematics of water-pyroclast equilibration. AB - The initial contact of external water with erupting magma and the mass ratio of water to magma govern the development of hydrovolcanic phenomena. The phase relations of water within the runout system and the separation of vapor or liquid from the pyroclasts explain gradational transitions between some pyroclastic flows, base surges, mud hurricanes, mudflows, and sheetfloods. PMID- 17746260 TI - Melting of normal hydrogen under high pressures between 20 and 300 kelvins. AB - The melting curve of normal hydrogen has been determined up to 52 kilobars between 20 and 300 Kelvins. The results are in excellent agreement with the modified Simon equation proposed for hydrogen below 19 kilobars, but not with the existing theoretical predictions. The results also provide an independent check on the validity of the ruby high-pressure scale at low temperature. PMID- 17746261 TI - Uninfected cells of soybean root nodules: ultrastructure suggests key role in ureide production. AB - In soybean root nodules, which export recently fixed nitrogen mainly as the ureides allantoin and allantoic acid, cells uninfected by rhizobia undergo a pronounced ultrastructural differentiation not shown by the infected cells, including enlargement of the microbodies and proliferation of smooth endoplasmic reticulum. Since some of the enzymes contributing to ureide synthesis occur in these subcellular components in root nodule preparations, the uninfected cells may participate in ureide synthesis and thus play an essential role in the symbiosis between host and bacterium. PMID- 17746262 TI - Control of calcium carbonate nucleation and crystal growth by soluble matrx of oyster shell. AB - A calcium-binding soluble protein extracted from oyster shell suppresses calcium carbonate nucleation and decreases the rate of crystal growth in vitro. These findings suggest that soluble matrix may regulate shell growth. PMID- 17746264 TI - Foot-length asymmetry, sex, and handedness. PMID- 17746263 TI - All-female fish: a cryptic species of menidia (atherinidae). AB - Electrophoretic evidence revealed the common occurrence of an all-female species of Menidia (Pisces: Atherinidae) at two localities separated by 280 kilometers on the Gulf Coast of Texas. This finding adds significantly to the known taxonomic spectrum of unisexuality in fishes and demonstrates that unisexuality may be more common among fishes that do not bear live young than is generally suspected. PMID- 17746265 TI - Foot-length asymmetry, sex, and handedness. PMID- 17746266 TI - Foot-length asymmetry, sex, and handedness. PMID- 17746267 TI - Identification of living and fossil bivalve larvae. PMID- 17746268 TI - This week in science. PMID- 17746271 TI - In reply: genetic engineering in agriculture. PMID- 17746270 TI - Genetic engineering in agriculture. PMID- 17746272 TI - Erratum. AB - In the article "Hughes Institute poised for growth" by Barbara J. Culliton (News and Comment, 7 June, p. 1178), Raymond Gesteland's name was spelled incorrectly. PMID- 17746274 TI - Engineering education. PMID- 17746275 TI - The very long baseline array. AB - The Very Long Baseline Array is a high-resolution synthesis radio telescope consisting of ten antennas, each 25 meters in diameter, located throughout the United States from Puerto Rico to Hawaii. Each antenna will be equipped with low noise receivers spaced throughout the frequency range from 330 megahertz to 43 gigahertz, a hydrogen-maser frequency standard for time and frequency reference, and broadband digital tape recorders. Tapes recorded at each antenna will be simultaneously replayed and correlated in a specially built digital correlator, and the correlator output will, by Fourier transformation, be used to construct images of celestial radio sources with an angular resolution better than one thousandth of an arc second. PMID- 17746269 TI - Genetic engineering in agriculture. PMID- 17746273 TI - Reusable oil plants? PMID- 17746277 TI - Europe Tries a Strategic Technology Initiative: Arguments for a European Research Coordination Agency (Eureka) have been political as much as technological and military as much as civilian. PMID- 17746278 TI - Proliferation Treaty Hinders SDI. PMID- 17746276 TI - Science and technology in India. AB - This assessment of the current status of science and technology in India focuses on developments in the areas of agriculture, energy, medicine, space, basic sciences, and engineering sciences. India has benefited in many fields from international collaboration during the last 30 years, but the country's leaders have also placed particularly strong emphasis on self-reliance. PMID- 17746279 TI - Selenium Poisons Refuge, California Politics: Drainage from the San Joaquin Valley has dumped selenium into a wildlife refuge and pitted two federal agencies against each other. PMID- 17746280 TI - Polish universities face crackdown. PMID- 17746281 TI - Supercomputer Restrictions Pose Problems for NSF, Universities. PMID- 17746282 TI - Fresh data on stale air. PMID- 17746283 TI - NRC Committee Blasts Immigration Statistics. PMID- 17746285 TI - Laurentide ice dynamics: late pleistocene history of northeastern new England and adjacent quebec. PMID- 17746284 TI - Pattern and Process in Life's History: Higher level selection processes are becoming acknowledged as important influences that shape the history of life. PMID- 17746286 TI - Developmental biology: pattern formation. PMID- 17746288 TI - Startle circuits: neural mechanisms of startle behavior. PMID- 17746287 TI - Antarctica and its biota: antarctic ecology. PMID- 17746289 TI - Near-Earth asteroids: possible sources from reflectance spectroscopy. AB - Spectra of near-Earth asteroids were compared to spectra of selected asteroids, planets, and satellites to determine possible source regions. The diversity of reflectance spectra of the near-Earth asteroids implies different mineralogical compositions and hence more than one source region. The presence of near-Earth asteroid spectral signatures similar to those of certain main-belt asteroids supports models that derive some of these asteroids from the 5:2 Kirkwood gap and the Flora family by gravitational perturbations. Planetary and satellite surfaces are different in composition than the near-Earth asteroids, which is in agreement with theoretical arguments that such bodies should not be sources. Some near Earth asteroids supply portions of Earth's meteorite flux, but other sources must also contribute. PMID- 17746290 TI - Phytoplankton blooming off the u.s. East coast: a satellite description. AB - A "bloom" of near-surface phytoplankton occurs in the Atlantic Slope region of the western Atlantic Ocean off the U.S. East Coast in the spring. Satellite time series of sea-surface temperature and phytoplankton pigment concentration, derived from measurements of the National Oceanic and Atmospheric Administration NOAA-7 Advanced Very-High-Resolution Radiometer and the National Aeronautics and Space Administration Nimbus-7 Coastal Zone Color Scanner, respectively, give information on the spatial extent and temporal development of such a bloom for a 28-day period in April through May 1982. The phytoplankton concentration of the slope area is comparable to that of the Atlantic Shelf. Total primary productivity of the slope during this period is equivalent to that of the shelf. The primary productivity within a warm-core ring and in the Gulf Stream system is less by a factor of 2. PMID- 17746291 TI - Insect Resistance to the Biological Insecticide Bacillus thuringiensis. AB - Resistance to the spore-crystal protein complex of Bacillus thuringiensis, the most widely used and intensively studied microbial insecticide, has been presumed to be unlikely to occur. In this study it was found that Plodia interpunctella, a major lepidopteran pest of stored grain products, can develop resistance to the insecticide within a few generations. Resistance increased nearly 30-fold in two generations in a strain reared on diet treated with Bacillus thuringiensis and after 15 generations reached a plateau 100 times higher than the control level. Resistance was stable when selection was discontinued. The resistance was inherited as a recessive trait. Plodia interpunctella strains collected from treated grain bins were more resistant than strains from untreated bins, indicating that the resistance can develop quickly in the field. PMID- 17746293 TI - THE NATIONAL ACADEMY OF SCIENCES. PMID- 17746292 TI - PRODUCTS AND MATERIALS Biochemical Analyzer. PMID- 17746294 TI - SOME AIDS TO THE STUDY OF STEREOSCOPIC VISION. PMID- 17746295 TI - CLASSIFICATION OF IGNEOUS ROCKS. PMID- 17746296 TI - THE DIVERSE FLORAS OF THE ROCKY MOUNTAIN REGION. PMID- 17746297 TI - CURRENT NOTES ON PHYSIOGRAPHY. PMID- 17746298 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17746299 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17746300 TI - NOTES ON INORGANIC CHEMISTRY. PMID- 17746301 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17746302 TI - THE PHILADELPHIA ZOOLOGICAL GARDEN. PMID- 17746303 TI - SOLOMON STRICKER. PMID- 17746304 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17746306 TI - MRS. PIPER, 'THE MEDIUM.'. PMID- 17746305 TI - DISCUSSION AND CORRESPONDENCE. PMID- 17746307 TI - A VIEW OF THE OHIO VALLEY IN 1755. PMID- 17746309 TI - LABORATORY TEACHING OF LARGE CLASSES. PMID- 17746308 TI - SCIENTIFIC JOURNALS. PMID- 17746310 TI - ORIGINAL RESEARCH AND CREATIVE AUTHORSHIP THE ESSENCE OF UNIVERSITY TEACHING. PMID- 17746312 TI - JAMES OWEN DORSEY. PMID- 17746311 TI - THE ARCHAeOLOGY OF SOUTHERN FLORIDA. PMID- 17746313 TI - THE EARLIEST GENERIC NAME OF AN AMERICAN DEER. PMID- 17746314 TI - DISCUSSION. PMID- 17746315 TI - Bingo. PMID- 17746316 TI - Stabilized Pinch and Controlled Fusion Power: Study of the pinch effect has caused ups and downs in the hopes for building a thermonuclear reactor. PMID- 17746317 TI - News of Science: Role of Director of Defense Research and Engineering under the Department of Defense Reorganization Act. PMID- 17746318 TI - Late Lower Silurian Fossils from Sillimanite Zone near Claremont, New Hampshire. PMID- 17746320 TI - Equipment. PMID- 17746321 TI - Map of India: correction. PMID- 17746322 TI - Fluorapatite and teeth. PMID- 17746323 TI - Refresher courses in education research. PMID- 17746324 TI - Laboratory animals for rheumatism research. PMID- 17746325 TI - Gaits of Horses: Marey's Studies. PMID- 17746326 TI - Robert hooke. PMID- 17746327 TI - Social science research and international relations. PMID- 17746328 TI - Biological material in meteorites: a review. PMID- 17746329 TI - Race and shared belief as factors in social choice. PMID- 17746330 TI - Acids and bases. PMID- 17746331 TI - Daddario Study Says NSF Should Be in Forefront of Policymaking. PMID- 17746332 TI - Foreign research: reuss criticizes projects supported by the United States. PMID- 17746333 TI - Earthquake Prediction: ESSA and USGS Vie for Leadership. PMID- 17746334 TI - Mica polytypes: systematic description and identification. AB - X-ray studies of mica specimens from a variety of geological localities show that biotite and certain lithium-rich mica samples are composed of a mixture of different polytypes. Many of the biotite structures are new complex polytypes not before reported. A new method of designating mica polytypes is proposed. Techniques are described for the systematic generation of all the possible layer stacking sequences of mica polytypes and for the verification of the stacking sequences in newly discovered forms. PMID- 17746335 TI - Salt rejection by a porous glass. AB - Porous glass partly filters dissolved salt from aqueous solutions passed through it under pressure. Rejection of salt can be increased by increase in the pH of the solution or by addition of Th(IV). The filtration seems to accord with a mechanism of salt exclusion characteristic of ion exchangers. PMID- 17746336 TI - Lunar experiments: the moon as a site for certain physical measurements. AB - If the lunar surface becomes available for conducting physical experiments, it may be particularly suited to thermal neutron and molecular and atomic beam measurements. The application of these beams for the purpose of communication on the lunar surface appears possible. PMID- 17746337 TI - Analysis of copper and brass coins of the early roman empire. AB - X-ray fluorescence analysis of 14 copper and brass coins of the early Roman Empire shows differences in composition between coins minted in Rome and in France. Concentrations of tin, lead, and antimony are nearly always less than in coins minted before 29 B.C. or after 54 A.D. Older coins were not melted to make copper coins of the early empire. PMID- 17746338 TI - Artificial Reestablishment of the Lichen Cladonia cristatella. AB - Slow drying stimulated the artificial development of fruiting structures by Cladonia cristatella Tuck. Fructification of the fungal partner occurred in the absence of its algal symbiont. Only newly isolated mycobionts produced the reproductive structures. Soredia and squamules were formed in response to the joint effect of slow drying and nutrient-poor conditions. PMID- 17746339 TI - Thermal stability of threonine in the presence of a marine polyphenolic material. AB - The rate of decomposition of threonine in 0.01M aqueous solution is unaffected by an equimolar concentration of pyrocatechol, but is increased by the addition of an extracellular polyphenolic material (3 mg/ml) produced by Fucus vesiculosus. Glycine, a pyrolytic product of threonine, behaves similarly. PMID- 17746340 TI - Phenylketonuria in rats: reversibility of behavorial deficit. AB - Phenylketonuria was induced in hooded rats by the conventional procedure of feeding excessive quantities of L-phenylalanine after weaning. Although this procedure reliably induced large, dose-dependent deficits in performance on a water maze, the behavioral deficits were completely eliminated after cessation of phenylalanine loading. These results cast doubt on the assumption that this animal preparation adequately simulates the irreversible intellectual impairments found in the child with late-detected phenylketonuria. PMID- 17746341 TI - Old faithful. PMID- 17746342 TI - Extraterrestrial dust as a source of atmospheric argon. PMID- 17746343 TI - Biology of hard tissues. PMID- 17746344 TI - Population growth. PMID- 17746345 TI - Forthcoming events. PMID- 17746346 TI - Letters to the editor. PMID- 17746347 TI - Perils of Disease--II. PMID- 17746348 TI - Our fragile environment. PMID- 17746349 TI - Don'T overlook berkeley. PMID- 17746350 TI - Our ears do deceive us. PMID- 17746351 TI - Mistaken identity. PMID- 17746352 TI - Letters to the EDitor. PMID- 17746354 TI - Desalination of cold seawater. PMID- 17746353 TI - Sonic Booms over Cities. PMID- 17746355 TI - Nonhuman primates. PMID- 17746357 TI - Postglacial vegetational history of the great plains. PMID- 17746356 TI - Particles that travel faster than light? PMID- 17746358 TI - Advances in Computer-based Education. PMID- 17746359 TI - Purpose and function of the university. PMID- 17746360 TI - Helium: costs jeopardize future of government conservation program. PMID- 17746361 TI - Environmental teach-in: university of michigan meeting. PMID- 17746362 TI - Research in britain: a non-weeping formula for living on tight funds. PMID- 17746365 TI - Laird seeks industry aid to defeat mansfield amendment. PMID- 17746364 TI - Foundations: taking stock after the tax reform bill. PMID- 17746366 TI - Galaxies and quasars: puzzling observations and bizarre theories. PMID- 17746367 TI - Ghar-i-Mordeh Gusfand (Cave of the Dead Sheep): A New Mousterian Locality in North Afghanistan. AB - The Middle Paleolithic of Central Asia is little known and less understood. Several sites have been excavated in Soviet Central Asia, but few have been adequately presented. Recent excavations in north Afghanistan may throw new light on the problem because of the size of the rock shelter involved and its relative geologic dating. PMID- 17746368 TI - Fit between Africa and Antarctica: A Continental Drift Reconstruction. AB - A computerized (smallest average misfit) best fit position is obtained for the juxtaposition of Africa and Antarctica in a continental drift reconstruction. An S-shaped portion of the Weddell and Princess Martha Coast regions of western East Antarctica is fitted into a similar profile along southeastern Africa. The total amount of overlap is 36,300 square kilometers, and the underlap is 23,600 square kilometers; the total mismatch is thus of 59,900 square kilometers. The congruency along the 1000-fathom isobath is remarkably good and suggests that this reconstruction is valid within the overall framework of the Gondwana supercontinent. PMID- 17746369 TI - Asexual reproduction in a sipunculan worm. AB - The sipunculan worm Aspidosiphon brocki reproduces asexually by transverse fision into two unequal parts, the smaller part comprising the posterior fifth of the animal. Prior to fission each part regenerates the structures essential to the formation of a new individual. The smaller posterior part (daughter) regenerates an anterior body, including introvert, anterior gut, retractor muscles, and nephridia, whereas the larger anterior part (parent) regenerates only the posterior body wall. PMID- 17746370 TI - Enhancement of photoalteration of cyclodiene insecticide chemical residues by rotenone. AB - When applied at low concentrations to plant foliage, rotenone catalyzes the photoisomerization of dieldrin and other cyclodiene insecticide chemical residues. This finding of a new type of interaction between pesticide chemicals suggests the possibility of controlling the persistence of residues on plants by use of certain pesticide-photosensitizer combinations and application sequences. PMID- 17746371 TI - Neuroendocrine control of ecdysis in silkmoths. AB - An adult moth sheds its pupal skin only during a specific period of the day. The brain is necessary for the synchronization of this behavior with the environmental photoperiod. This function is fully preserved when all the brain's nervous connections are severed or when a "loose" brain is transplanted into the tip of the abdomen. By appropriate experiments it was possible to show that the entire mechanism is brain-centered. The components include a photoreceptor mechanism, a clock, and a neuroendocrine output. The clock-controlled release of the hormone acts on the central nervous system to trigger a species-specific behavior pattern which culminates in ecdysis. PMID- 17746372 TI - Plant-Pathogenic Mycoplasma-Like Organism: Maintenance in vitro and Transmission to Zea mays L. AB - Mycoplasma-like bodies, isolated from corn plants that were infected with Rio Grande strain of corn stunt, were maintained in an artificial cell-free medium. The agent apparently multiplied. Leafhopper vectors that were injected with the pure cultures transmitted the agent to healthy corn plants and induced the corn stunt disease. PMID- 17746373 TI - Differentiation of populations. PMID- 17746374 TI - Bed forms in base-surge deposits: lunar implications. PMID- 17746375 TI - Bark beetle pheromones. PMID- 17746376 TI - Radiation biology of the fetal and juvenile mammal. PMID- 17746377 TI - Forthcoming events. PMID- 17746378 TI - This Week in SCIENCE. PMID- 17746379 TI - Sciencescope. PMID- 17746380 TI - Thumbs up for two detectors. PMID- 17746381 TI - Hope from a hot little motor. PMID- 17746383 TI - Keeping textbook babble at bay. PMID- 17746382 TI - Johnson vs. Darwin. PMID- 17746384 TI - Genes score a new point in alcoholism. PMID- 17746385 TI - Abortion law fallout. PMID- 17746386 TI - Seeing stars in a handful of dust. PMID- 17746387 TI - Scooping starstuff from a comet. PMID- 17746388 TI - Mix well, then apply: math meeting in d.C.: curse foiled--again. PMID- 17746389 TI - Mix well, then apply: math meeting in d.C.: goodbye assembly line. PMID- 17746390 TI - A most improbable planet. PMID- 17746391 TI - Microbial math. PMID- 17746393 TI - The small wonders of microengineering. PMID- 17746392 TI - A mountaintop cliffhanger of an eclipse. PMID- 17746394 TI - Statistical data analysis in the computer age. AB - Most of our familiar statistical methods, such as hypothesis testing, linear regression, analysis of variance, and maximum likelihood estimation, were designed to be implemented on mechanical calculators. Modern electronic computation has encouraged a host of new statistical methods that require fewer distributional assumptions than their predecessors and can be applied to more complicated statistical estimators. These methods allow the scientist to explore and describe data and draw valid statistical inferences without the usual concerns for mathematical tractability. This is possible because traditional methods of mathematical analysis are replaced by specially constructed computer algorithms. Mathematics has not disappeared from statistical theory. It is the main method for deciding which algorithms are correct and efficient tools for automating statistical inference. PMID- 17746395 TI - Enols and other reactive species. AB - Rapid advances in the chemistry of enols and other reactive species have been made possible recently by the development of methods for generating these short lived substances in solution under conditions where they can be observed directly and their reactions can be monitored accurately. New laboratory techniques are described and a sample of the new chemistry they have made available is provided; special attention is given to ynols and ynamines and the remarkable effects that the carbon-carbon triple bonds of these substances have on their acid-base properties. PMID- 17746396 TI - High-pressure chemistry of hydrogen in metals: in situ study of iron hydride. AB - Optical observations and x-ray diffraction measurements of the reaction between iron and hydrogen at high pressure to form iron hydride are described. The reaction is associated with a sudden pressure-induced expansion at 3.5 gigapascals of iron samples immersed in fluid hydrogen. Synchrotron x-ray diffraction measurements carried out to 62 gigapascals demonstrate that iron hydride has a double hexagonal close-packed structure, a cell volume up to 17% larger than pure iron, and a stoichiometry close to FeH. These results greatly extend the pressure range over which the technologically important iron-hydrogen phase diagram has been characterized and have implications for problems ranging from hydrogen degradation and embrittlement of ferrous metals to the presence of hydrogen in Earth's metallic core. PMID- 17746397 TI - Commensurability and mobility in two-dimensional molecular patterns on graphite. AB - Two-dimensional molecular patterns were obtained by the adsorption of long-chain alkanes, alcohols, fatty acids, and a dialkylbenzene from organic solutions onto the basal plane of graphite. In situ scanning tunneling microscopy (STM) studies revealed that these molecules organize in lamellae with the extended alkyl chains oriented parallel to a lattice axis within the basal plane of graphite. The planes of the carbon skeletons, however, can be oriented either predominantly perpendicular to or predominantly parallel with the substrate surface, causing the lamellar lattice to be either in or near registry with the substrate (alkanes and alcohols) or not in registry (fatty acids and dialkylbenzenes). In the case of the alcohols and the dialkylbenzene the molecular axes are tilted by +30 degrees or -30 degrees with respect to an axis normal to the lamella boundaries, giving rise to molecularly well-defined domain boundaries. Fast STM image recording allowed the spontaneous switch between the two tilt angles to be observed in the alcohol monolayers on a time scale of a few milliseconds. PMID- 17746398 TI - Dislocations and Flux Pinning in YBa2Cu3O7-delta. AB - Bulk YBa(2)Cu(3)O(7-delta) superconductors, under certain processing conditions such as melt texturing, exhibit a very high dislocation density of 10(9) to 10(10) per square centimeter. In addition, the density of low-angle grain boundaries in such samples can be significantly increased (to less than 700 nanometer spacing) through a dispersion of submicrometer-sized Y(2)BaCuO(5) inclusions. These defect densities are comparable to those in high critical current thin films as revealed through scanning tunneling microscopy, and yet the critical current densities in the bulk materials (at 77 kelvin and a field of 1 tesla for example) remain at a 10(4) amperes per square centimeter level, about two orders of magnitude lower than in thin films. The results imply that these defect density levels are not significant enough to explain the difference in flux pinning strength between the thin film and bulk materials. The observation of spiral-like growth of the superconductor phase in bulk Y-Ba-Cu-O is also reported. PMID- 17746399 TI - Order and Disorder in C60 and KxC60 Multilayers: Direct Imaging with Scanning Tunneling Microscopy. AB - Monolayer and multilayer structures of C(60), a high temperature van der Waals solid, have been studied with scanning tunneling microscopy. Structures grown on GaAs(110) at 300 kelvin and at elevated temperatures show significantly different morphologies because of balances between thermodynamics and kinetics. Condensation onto stepped surfaces demonstrates preferred bonding and nucleation at step edges. Detailed studies of potassium incorporation in crystalline C(60) show highly ordered structures in the K(3)C(60) metallic state but disordered non metallic structures for high potassium concentrations. PMID- 17746400 TI - Conversion of ectoderm to mesoderm by cytoplasmic extrusion in leech embryos. AB - The role of cytoplasmic domains in the determination of the fates of ectodermal and mesodermal cells has been investigated in leech embryos. When yolk-deficient cytoplasm (teloplasm) was extruded from the animal pole of the zygote, the ectodermal precursor blastomere was converted to a mesodermal fate. This change of fate can be prevented by replacement of the extruded animal teloplasm with teloplasm from the vegetal pole. The fate of the mesodermal precursor blastomere was unaffected by teloplasm extrusion or rearrangement. These results demonstrate that ectodermal and mesodermal determination offate involves a binary decision dependent on the position of teloplasm along the animal-vegetal axis. PMID- 17746401 TI - Response. PMID- 17746402 TI - The spectrum of comet austin. PMID- 17746403 TI - 1991 Bell Atlantic--AAAS Institute Teachers. PMID- 17746404 TI - Scientists invited to join teachers in fight against scientific illiteracy. PMID- 17746405 TI - Reviewers wanted. PMID- 17746406 TI - In memory of arthur herschman. PMID- 17746407 TI - A cultural transplant. PMID- 17746408 TI - The unfolding of a philosophy. PMID- 17746409 TI - Approaches to systematics. PMID- 17746410 TI - Beneath continents. PMID- 17746411 TI - Products & materials. PMID- 17746412 TI - SCIENCE NEWS. PMID- 17746413 TI - The Role of Pure Science. PMID- 17746414 TI - THE HISTORY OF MATHEMATICS FORTY YEARS AGO. PMID- 17746415 TI - MEDITERRANEAN SEDIMENTS AND PLEISTOCENE SEA LEVELS. PMID- 17746416 TI - TYROSINE DETERMINATIONS CARL REITER. PMID- 17746417 TI - VOCAL PITCH DURING SIMULATED EMOTION. PMID- 17746418 TI - PHOSPHORUS METABOLISM OF CHICKS AFFLICTED WITH PEROSIS. PMID- 17746420 TI - AN IMPROVED APPARATUS FOR THE SERIAL SECTIONING OF FOSSILS. PMID- 17746419 TI - THE GROWTH OF LEPTOSPIRA ICTEROHEMORRHAGIAE ON THE CHORIOALLANTOIC MEMBRANE OF THE CHICK EMBRYO. PMID- 17746421 TI - A MICRO-CONDUCTIVITY CELL OF SIMPLE DESIGN. PMID- 17746423 TI - High-Temperature Research: By means of "liquid containers," liquid metals can be studied at much higher temperatures than heretofore. PMID- 17746422 TI - International Competition in Science. PMID- 17746424 TI - Space Budget: Opposition Grows as Scientists, Congressmen, Voice Concern about Lunar Landing Goal. PMID- 17746426 TI - AID: Almost Everyone Favors Research on Development Problems But Going Has Not Been Smooth. PMID- 17746425 TI - Birth Control: Catholic Opinion Varies Widely on Rock's New Book. PMID- 17746427 TI - Disarmament Agency: A New Look in ACDA's Research Programs. PMID- 17746428 TI - Project Westford: Air Force Experiment Opens Successfully. PMID- 17746429 TI - Hailsham vs. Cambridge: British Science Minister Will Get Degree. PMID- 17746430 TI - Federal Grant Policy: Academy Requested to Undertake Study. AB - The council of the National Academy of Sciences, at its 8 June meeting, will consider a request from the American Society of Biological Chemists that the Academy undertake a review of the government's research grant policies. The request, in a resolution passed by the society's membership at its April meeting, reflects growing concern, both scientific and political, over the relationships between federal agencies and their grantees. The resolution follows. PMID- 17746431 TI - Food for Thought. PMID- 17746433 TI - Repeatability of Jupiter's Decametric Radio Emission. PMID- 17746432 TI - Oxygen-Carrying Properties of a Simple Synthetic System. AB - An iridium compound, chloro-carbonyl-bis(triphenylphosphine)-iridium, in solution, takes up molecular oxygen-one molecule per metal atom-which is subsequently recovered by reducing the pressure. The adduct is photosensitive but otherwise stable at ambient temperatures. It is a monomeric molecular complex and probably contains a peroxo group with both oxygens bonded to the same metal atom. PMID- 17746434 TI - Carbon: A New Crystalline Phase. AB - The electrical resistance of single crystal graphite shows a very sharp increase at above 150 kilobars, accompanied by a drifting upward with time. The behavior is typical of a first-order phase transition, and is irreversible. X-rays on the material after removal from the cell show lines of a new material with a structure which can be indexed as a cubic lattice with a unit cell edge of 5.545 angstroms. The density of the new phase is estimated at 2.80 grams per cubic centimeter. PMID- 17746435 TI - Helicoplacoidea: A New Class of Echinoderms. AB - A fusiform, spirally coiled and pleated, free-living, heavily placate echinoderm with an expansible test has been discovered in the Lower Cambrian Olenellus zone of California. It is characterized by 10 "interambulacral" areas, a single principal endothecal ambulacrum with a short branch, and oral and apical regions at opposite poles. A new class, the Helicoplacoidea is proposed for the new genus Helicoplacus, with two new species, H. gilberti (type species) and H. curtisi. PMID- 17746436 TI - Siphonophores and the Deep Scattering Layer. AB - Bathyscaphe dives in the San Diego Trough have revealed a close spatial relation between siphonophores and the deep scattering layer as recorded by precision depth recording echo-sounders. Measurements of gas bubbles within the flotation structures of Nanomia bijuga captured in a closing net in an ascended scattering layer indicate that these are very close to the resonant size for 12-kcy/sec sound. Because such organisms are capable of making prolonged vertical migrations, and are widespread geographically, they are very probably the major cause of stratified zones of scattering throughout the oceans of the world. PMID- 17746437 TI - Electroconvulsive Threshold Elevation: From Daily Stimulation of Adrenalectomized Animals. AB - The elevation of electroconvulsive threshold, which develops in cats during repeated daily measurements threof might result from an increased production of deoxycorticosterone. Bilateral adrenalectomy followed by maintenance on deoxycorticosterone and cortisone in fixed dosages did not prevent subsequent elevation of the threshold in either cats or miniature dogs. The elevation rate in the adrenalectomized dogs exceeded that in the intact control dogs. This elevation, which resembles tolerance, in the intact cat or miniature dogs, is not dependent on an increased production of adrenocortical hormones; it may more likely be the result of cerebral rather than extracerebral adaptation. PMID- 17746438 TI - ANOTHER VIEW OF ECONOMIC LAWS AND METHODS. PMID- 17746440 TI - DRAWING IN PUBLIC SCHOOLS. PMID- 17746439 TI - CHINESE REVENUES AND SYSTEMS OF TAXATION. PMID- 17746441 TI - PRESTWICH'S GEOLOGY. PMID- 17746443 TI - PORTER'S MECHANICS AND FAITH. PMID- 17746442 TI - TRIUMPHANT DEMOCRACY. PMID- 17746444 TI - SCIENCE NEWS. PMID- 17746445 TI - THE TAXONOMIC OUTLOOK IN ZOOLOGY. PMID- 17746446 TI - THE USEFULNESS OF PSYCHOLOGY. PMID- 17746447 TI - THE NEED FOR AND THE PROPOSAL OF A NEW GENETIC TERM. PMID- 17746448 TI - MUSICAL PITCH AND THE PHYSICISTS. PMID- 17746449 TI - THE DETERMINATION OF CARBONATES IN SOIL. PMID- 17746450 TI - PHYSIOLOGY OF RARE GASES. PMID- 17746451 TI - THE RATE OF GROWTH OF STALACTITES. PMID- 17746452 TI - BLACK PAPER FOR CAMERA LUCIDA DRAWINGS. PMID- 17746453 TI - GEOGRAPHICAL INDEX NUMBERS. PMID- 17746454 TI - OVERWINTERING OF THE FIRE BLIGHT PATHOGEN, BACILLUS AMYLOVORUS, WITHIN THE BEEHIVE. PMID- 17746455 TI - EDUCATIONAL DARKNESS AND LUMINOUS RESEARCH. PMID- 17746456 TI - RESEARCH AT MELLON INSTITUTE DURING 1937-38. PMID- 17746457 TI - FORCE IN MECHANICS. PMID- 17746458 TI - DISTRIBUTION OF REPRINTS OF PAPERS BY THE LATE BASHFORD DEAN. PMID- 17746459 TI - NEW FOSSIL LOCALITIES IN THE DURHAM TRIASSIC BASIN. PMID- 17746460 TI - EFFECT ON ROOT FORMATION OF RETREATING CUTTINGS WITH GROWTH SUBSTANCES. PMID- 17746461 TI - THE AMERICAN PHILOSOPHICAL SOCIETY. PMID- 17746462 TI - THE LARVAL DEVELOPMENT OF DRAGONFLIES OF THE GENUS AESHNA. PMID- 17746463 TI - A PHYSIOLOGICAL STUDY OF THE RIND COLOR OF CERTAIN CITRUS FRUITS. PMID- 17746464 TI - THE MOLECULAR WEIGHTS OF UREASE, CANAVALIN, CONCANAVALIN A AND CONCANAVALIN B. PMID- 17746465 TI - METHYL METHACRYLATE AS A LABORATORY TOOL. PMID- 17746466 TI - SOME EFFECTS OF ANDROSTERONE ON SEXUAL DEVELOPMENT IN THE FEMALE RAT. PMID- 17746467 TI - A SIMPLE FEEDER FOR RATS AND MICE. PMID- 17746468 TI - This week in science. PMID- 17746470 TI - American Weapons, Alien Parts: Like computers and cassette players, the brains of U.S. missiles may soon be made in Japan. Some see this as a risky business. PMID- 17746469 TI - Transportation of hazardous materials. PMID- 17746471 TI - Soviets discuss sverdlovsk. PMID- 17746473 TI - BP Looks for Remarkable Research Projects. PMID- 17746472 TI - Red Tape Snarls Soviet Research Ship: An effort to encourage international participation in an oceanographic research cruise was foiled by snafus in obtaining docking permits. PMID- 17746474 TI - Damage to Tropical Forests, or Why Were There So Many Kinds of Animals?: Just as biologists are discovering that there are more species of animals and plants on Earth than was previously estimated, the ravages of habitat destruction are beginning to devastate biological diversity, in most cases before individual species have become known to science. PMID- 17746475 TI - In Search of Dark Matter: Through the telescope, some 90% of the mass in the universe seems to be invisible; in the laboratory, however, a new generation of detectors may bring the dark matter to light. PMID- 17746476 TI - Quasars at 25. AB - In the quarter century since the first optical identification of a "radio star" (3C 48), astronomers have come to general agreement that the underlying quasar energy source is accretion onto a massive black hole. There is much less agreement on the detailed physics of the processes by which this energy is converted to the forms observed, but this has not prevented the objects from serving as valuable probes of the universe at distant times and places. PMID- 17746477 TI - Experimental methods in the political economy of exchange. AB - Traditionally, economics has been considered a nonexperimental science. In the last quarter century experimental methods have become a growing part of the economist's effort to more fully understand how individual motivation, individual information, and exchange rules relate to market outcomes in different institutions. Empirical support has been found in a wide variety of different experiments for the theoretical proposition that markets serve to aggregate the dispersed information of individuals to produce wealth-creating outcomes for society. A number of different experiments are presented to illustrate the type of questions addressed, including some in which the process is governed by political institutions such as majority rule. PMID- 17746479 TI - Lightning strike fusion: extreme reduction and metal-silicate liquid immiscibility. AB - A glassy fulgurite, formed recently on a morainal ridge in southeastern Michigan, contains micrometer- to centimeter-sized metallic globules rich in native silicon, which unmixed from a silica-rich liquid. The unusual character of these globules and their potential for elucidating conditions of fulgurite formation prompted further study. Thermodynamic calculations indicate that temperatures in excess of 2000 K and reducing conditions approaching those of the SiO(2)-Si buffer were needed to form the coexisting metallic and silicate liquids. The phases produced are among the most highly reduced naturally occurring materials known. Some occurrences of other highly reduced minerals may also be due to lightning strike reduction. Extreme reduction and volatilization may also occur during high-temperature events such as lightning strikes in presolar nebulae and impacts of extraterrestrial bodies. As a result of scavenging of platinum-group elements by highly reduced metallic liquids, geochemical anomalies associated with the Cretaceous-Tertiary boundary may have a significant terrestrial component even if produced through bolide impact. PMID- 17746478 TI - Very long baseline interferometric observations made with an orbiting radio telescope. AB - An orbiting spacecraft and ground observatories have been used to obtain interferometric observations of cosmic radio sources. The Tracking and Data Relay Satellite System (TDRSS) was used as the orbiting observatory in conjunction with two 64- meter radio telescopes at ground observatories, one in Australia and one in Japan. The quasars 1730-130 (NRAO 530), 1510-089, and 1741-038 were observed at a frequency of 2.3 gigahertz, and a maximum projected baseline of 1.4 earth diameters was achieved. All quasar observations for which valid data were acquired resulted in detected fringes. Many of the techniques proposed for a dedicated very long baseline interferometry observatory in space were used successfully in this experiment. PMID- 17746480 TI - Miocene characid fishes from Colombia: evolutionary stasis and extirpation. AB - Fossil fishes from the Miocene La Venta fauna of the Magdalena River Valley, Colombia, are identified as Colossoma macropomum (Characidae), a living species from the Orinoco and Amazon basins. The fossils document a long and conservative history for a species that is highly specialized for feeding on streamside plants. The phylogenetically advanced position of Colossoma in the subfamily Serrasalminae implies that six related genera and other higher characid taxa originated well before 15 million years ago. This discovery also corroborates neontological evidence for a vicariance event that contributed species from Miocene Orinoco-Amazon faunas to the original Magdalena region fauna. The fossils suggest a formerly diverse Magdalena fauna that has suffered local extinction, perhaps associated with late Cenozoic tectonism. This new evidence may help explain the depauperate nature of the modern Magdalena River. PMID- 17746481 TI - A single genetic unit specifies two transposition functions in the maize element activator. AB - The self-mobile maize transposable element Ac (Activator) displays two trans acting genetic functions: it induces transposition of the element Ds (Dissociation) but, as its dosage is increased, it also inhibits transposition. Previous work has shown that the 4563 base pair (bp)-long Ac element contains three open reading frames (ORF's) and that a deletion in ORF 1 in wx-m9(Ds), a Ds derivative from Ac isolated at the wx (waxy) locus, results in loss of transposition. The Ds element in the bronze allele bz-m2(DI) is shown to have arisen from Ac by a 1312-bp deletion that is located almost entirely within ORF 2 and does not affect ORF 1. The Ds elements in wx-m9(Ds) and bzm2(DI), defective in ORF 1 and ORF 2, respectively, do not complement genetically to restore the transposition function of Ac; therefore, this function must be specified jointly by ORF's 1 and 2. Furthermore, since bz-m2(DI) does not contribute to Ac's inhibitory dosage effect, both Ac properties result from the expression of the same genetic functional unit. PMID- 17746482 TI - AAAS announces its first annual colloquium on science, arms control, and national security..: Science and Security: The Future of Arms Control. PMID- 17746484 TI - Hopes from technology: imagining tomorrow. PMID- 17746483 TI - Gordon research conferences: 1987 winter schedule. PMID- 17746485 TI - Pharmacogenetics: ethnic differences in reactions to drugs and xenobiotics. PMID- 17746486 TI - Family decision making: the economics of women, men, and work. PMID- 17746487 TI - Fish behavior: the behavior of teleost fishes. PMID- 17746488 TI - Products & materials. PMID- 17746489 TI - This week in science. PMID- 17746490 TI - In reply: u.s.-China collaboration. PMID- 17746491 TI - Swimming for dear memory. PMID- 17746492 TI - Circuit boards: heal yourselves. PMID- 17746493 TI - A Prism for Electrons: Treating electrons like photons opens up a world of electronics that is not restricted to the simple on/off states of transistors. PMID- 17746494 TI - Glasnost, greenhouses, and ice ages. PMID- 17746495 TI - Solar neutrino deficit confirmed? PMID- 17746496 TI - Big number breakdown. PMID- 17746498 TI - British study endorses chiropractic. PMID- 17746499 TI - "Turing test" prize. PMID- 17746497 TI - NASA Scrubs Martian Instrument Package. PMID- 17746501 TI - Extension service for industry? PMID- 17746500 TI - Catch some rays. PMID- 17746502 TI - Experiments with separated oscillatory fields and hydrogen masers. AB - Descriptions are given of the methods of separated and successive oscillatory fields and of the atomic hydrogen maser. Their applications to the precision spectroscopy of atoms and molecules are discussed along with specific examples of fundamental measurements best made with such devices. The applications of these methods to atomic clocks are discussed. Cesium-separated oscillatory fields atomic beam clocks are accurate to 10(-13), and hydrogen masers are stable for several hours to 10(-15). A discussion is given of fundamental experiments that require highly stable clocks, such as long-base-line radio astronomy, precise measurement of pulsar frequencies and stabilities, tests of relativity theories, and accurate navigation both on the earth and in outer space. PMID- 17746503 TI - Influence of environmental quality on pollen competitive ability in wild radish. AB - Pollen of Raphanus raphanistrum produced under low nutrient conditions sired fewer seeds than pollen produced under better conditions when the two types were applied on a stigma together. No difference was seen in single-donor crosses. Male mating success can be strongly influenced by the environmental conditions of pollen-bearing plants, a factor overlooked in studies of plant reproductive biology and in standard quantitative genetic crossing designs, where effects of male parent are equated with heritable genetic variation. PMID- 17746504 TI - Synthesis of phytoalexins in sorghum as a site-specific response to fungal ingress. AB - Sorghum produces phytoalexins that are 3-deoxyanthocyanidin flavonoids. The compounds inhibit the growth of phytopathogenic fungi in vitro. The phytoalexins appear to be synthesized in subcellular inclusions within a host epidermal cell that is about to be penetrated by a fungus. This site-restricted synthesis suggests that the phytoalexin response occurs initially in the first cells that come under fungal attack and is not simply a response of cells that surround the original infection site. PMID- 17746505 TI - Scale and Scope. The Dynamics of Industrial Capitalism. Alfred D. Chandler, Jr., with the assistance of Takashi Hikino. Belknap (Harvard University Press), Cambridge, MA, 1990. xx, 860 pp. $35. PMID- 17746506 TI - Vision and the Emergence of Meaning. Blind and Sighted Children's Early Language. Anne Dunlea. Cambridge University Press, New York, 1990. xvi, 196 pp., illus. $39.50. PMID- 17746507 TI - Computing Before Computers. William Aspray, Ed. Iowa State University Press, Ames, 1990. x, 266 pp., illus. $27.95. PMID- 17746508 TI - Analogies Between Analogies. The Mathematical Reports of S. M. Ulam and His Los Alamos Collaborators. A. R. Bednarek and Francoise Ulam, Eds. University of California Press, Berkeley, 1990, xviii, 565 pp., illus. $60. Los Alamos Series in Basic and Applied Sciences, 10. PMID- 17746510 TI - ACCURACY IN THERMOMETERS. PMID- 17746509 TI - THE ANTHROPOLOGICAL SOCIETY OF WASHINGTON. PMID- 17746511 TI - THE PRIORITY OF THE LATE FRIEDRICH MOIIR IN REGARD TO THE PRINCIPLE OF THE CONSERVATION OF ENERGY. PMID- 17746513 TI - MICROSCOPY: NEW CELL FOR OPAQUE OBJECTS. PMID- 17746512 TI - WYANDOTTE GOVERNMENT: A Short Study of Tribal Society, Delivered at the Boston Meeting of the American Association for the dvancement of Science, August 1, 1880. PMID- 17746514 TI - THE GENESIS OF CERTAIN IRON ORES. PMID- 17746516 TI - THE TWO KINDS OF VIVISECTION-- SENTISECTION AND CALLISECTION. PMID- 17746515 TI - FEELING AND FUNCTION AS FACTORS IN HUMAN DEVELOPMENT. PMID- 17746518 TI - SOME OF THE INFUSORIA FOUND IN FRESH POND, CAMBRIDGE. PMID- 17746517 TI - PROFESSOR EDWARD D. COPE. PMID- 17746519 TI - TWO NEW METHODS OF FIGHTING INJURIOUS INSECTS. PMID- 17746521 TI - THE ORIGIN OF THE PINK BOLLWORM. PMID- 17746520 TI - MAGNETIZATION BY ROTATION. PMID- 17746522 TI - HARRY KIRKE WOLFE. PMID- 17746523 TI - RED RAYS AND PHOTOELECTRIC EFFECT. PMID- 17746525 TI - THE PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES. PMID- 17746524 TI - SPECIAL GROWTH-PROMOTING SUBSTANCES AND CORRELATION. PMID- 17746527 TI - REASON FOR THE HELPFUL EFFECT OF ALCOHOLIC BEVERAGES IN DIABETES, STATES OF DEPRESSION, AND CONVALESCENCE. PMID- 17746526 TI - INVESTIGATIONS ON THE IMBIBITION OF WATER BY GELATINE. PMID- 17746528 TI - This week in science. PMID- 17746530 TI - Sampling zooplankton: correction. PMID- 17746529 TI - Response. PMID- 17746531 TI - Sciencescope. PMID- 17746533 TI - Report advocates "value-added" ph.d. PMID- 17746532 TI - Academy fends off charges of bias. PMID- 17746534 TI - In the u.s., engineers oust old regime. PMID- 17746536 TI - NASA Panel Would Drop Ames Lab. PMID- 17746535 TI - Partisan politics comes to the fore. PMID- 17746537 TI - U.s. Climate tilts toward the greenhouse. PMID- 17746539 TI - Adaptive hatching. PMID- 17746538 TI - Dwarfs and dim galaxies mark limits of knowledge. AB - When 250 astronomers met in Cardiff early this month at the U.K. National Astronomy Meeting, sponsored by the Royal Astronomical Society and the Particle Physics and Astronomy Research Council, they grappled with some big problems, among them the age of the universe and its mass. They also took on an even bigger metaproblem: How confident can they be in their knowledge about cosmic origins? PMID- 17746540 TI - DNA testing detente? PMID- 17746541 TI - Transplant surgeon indicted. PMID- 17746542 TI - Varmus scraps drug-pricing clause. PMID- 17746543 TI - The silica balance in the world ocean: a reestimate. AB - The net inputs of silicic acid (dissolved silica) to the world ocean have been revised to 6.1 +/- 2.0 teramoles of silicon per year (1 teramole = 10(12) moles). The major contribution (about 80 percent) comes from rivers, whose world average silicic acid concentration is 150 micromolar. These inputs are reasonably balanced by the net ouputs of biogenic silica of 7.1 +/- 1.8 teramoles of silicon per year in modern marine sediments. The gross production of biogenic silica (the transformation of dissolved silicate to particulate skeletal material) in surface waters was estimated to be 240 +/- 40 teramoles of silicon per year, and the preservation ratio (opal accumulation in sediment/gross production in surface waters) averages 3 percent. In the world ocean the residence time of silicon, relative to total biological uptake in surface waters, is about 400 years. PMID- 17746544 TI - Continent-ocean chemical heterogeneity in the mantle based on seismic tomography. AB - Seismic models of global-scale lateral heterogeneity in the mantle show systematic differences below continents and oceans that are too large to be purely thermal in origin. An inversion of the geoid, based on a seismic model that includes viscous flow in the mantle, indicates that the differences beneath continents and oceans can be accounted for by differences in composition in the upper mantle superposed on mantle-wide thermal heterogeneities. The net continent ocean density differences, integrated over depth, are small and cause only a low flux of mass and heat across the asthenosphere and mantle transition zone. PMID- 17746546 TI - The collapse of free polymer chains in a network. AB - The conformation of linear polymer chains trapped in a matrix of cross-linked polymer has been measured by neutron scattering. Three regimes were found depending on the length of the linear chain, Nl, with respect to the mesh size of the network, N(c). When N(c) > Nl, the radius of gyration, R(g), of the linear chain is the same as that observed in the uncrosslinked melt. When N(c) < Nl, R(g) shrinks according to the scaling relation R(g)(-1) approximately N(c)(-1) that has been predicted for isolated polymer chains trapped in a field of random obstacles. When N(c) << Nl the linear chains are observed to segregate. PMID- 17746545 TI - Seismic Images of Active Magma Systems Beneath the East Pacific Rise Between 17{degrees}05' and 17{degrees}35'S. AB - Seismic reflection data from the East Pacific Rise between 17 degrees 05' and 17 degrees 35'S image a magma lens that varies regularly in depth and width as ridge morphology changes, confirming the notion that axial morphology can be used to infer ridge magmatic state. However, at 17 degrees 26'S, where the ridge is locally shallow and broad, the magma lens is markedly shallower and wider than predicted from regional trends. In this area, submersible dives reveal recent volcanic eruptions. These observations indicate that it is where the width and depth of the magma chamber differ from regional trends, indicating an enhanced magmatic budget, that is diagnostic of current magmatism. PMID- 17746547 TI - High-temperature molecular magnets based on cyanovanadate building blocks: spontaneous magnetization at 230 k. AB - The molecular-based magnetic materials Cs(2)Mn(||)[V(||)(CN)(6)] (1) and (Et(4)N)(0.5)Mn(l.25)- [V(CN)(5)].2H(2)O (2) (where Et is ethyl) were prepared by the addition of manganese(II) triflate to aqueous solutions of the hexacyanovanadate(II) ion at 0 degrees C. Whereas 1 crystallizes in a face centered cubic lattice, 2 crystallizes in a noncubic space group. The cesium salt (1) has features characteristic of a three-dimensional ferrimagnet with a Neel transition at 125 kelvin. The tetraethylammonium salt (2) also behaves as a three dimensional ferrimagnet with a Neel temperature of 230 kelvin; only two other molecular magnets have higher magnetic ordering temperatures. Saturation magnetization measurements indicate that in both compounds the V(II) and high spin Mn(II) centers are antiferromagnetically coupled. Both 1 and 2 exhibit hysteresis loops characteristic of soft magnets below their magnetic phase transition temperatures. The high magnetic ordering temperatures of these cyano bridged solids confirm that the incorporation of early transition elements into the lattice promotes stronger magnetic coupling by enhancing the backbonding into the cyanide pi* orbitals. PMID- 17746549 TI - Response. PMID- 17746548 TI - Orientational and Magnetic Ordering of Buckyballs in TDAE-C60. AB - Spin ordering in the low-temperature magnetic phase is directly linked to the orientational ordering of C(60) molecules in organically doped fullerene derivatives. Electron spin resonance and alternating current susceptometry measurements on tetrakis(dimethylamino)ethylene-C(60) (TDAE-C(60)) (Curie temperature T(c) = 16 kelvin) show a direct coupling between spin and merohedral degrees of freedom. This coupling was experimentally demonstrated by showing that ordering the spins in the magnetic phase imprints a merohedral order on the solid or, conversely, that merohedrally ordering the C(60) molecules influences the spin order at low temperature. The merohedral disorder gives rise to a distribution of pi-lectron exchange interactions between spins on neighboring C(60) molecules, suggesting a microscopic origin for the observed spinglass behavior of the magnetic state. PMID- 17746551 TI - Other books of interest. PMID- 17746550 TI - Response. PMID- 17746552 TI - Vignettes: psychopharmacology. PMID- 17746553 TI - Products & materials. PMID- 17746554 TI - Behind the Times. PMID- 17746555 TI - The New American Archeology: Its changing interests are bringing new kinds of understanding and a generalized view of its problems. PMID- 17746556 TI - Cloud Physics: Not all questions about nucleation, growth, and precipitation of water particles are yet answered. PMID- 17746557 TI - Alvin Seale, Naturalist and Ichthyologist. PMID- 17746558 TI - News of Science: Federal Budget Sets Research and Development Funds at $5.5 Billion with Emphasis on Space Activities. PMID- 17746562 TI - Equipment. PMID- 17746559 TI - Erratum. AB - The levels enzyme activity given in Table 1 of the report, "Red Cell Glucose-6 Phosphate and 6-Phosphogluconic Dehydrogenases and Nucleoside Phosphorylase," by P. A. Marks [Science 127, 1338 (1958)] are incorrect by a factor of 10(3). All activity levels should read per 10(9), not 10(6), erythrocytes. PMID- 17746560 TI - Earth Oblateness in Terms of Satellite Orbital Periods. AB - A theoretical equation relating the earth's oblateness to the anomalistic and nodical periods and orbit parameters of an earth satellite is presented. In the absence of exact data on nodical periods, Vanguard prediction data are utilized to obtain a check calculation for the oblateness and to establish the validity of the method. PMID- 17746563 TI - Article. PMID- 17746564 TI - Teaching and Research. PMID- 17746565 TI - Adenine and Plant Growth. PMID- 17746566 TI - This week in science. PMID- 17746567 TI - Beauty, balance, and mathematics. PMID- 17746568 TI - Protein structure. PMID- 17746570 TI - NASA's Bureaucracy. PMID- 17746569 TI - NASA's Bureaucracy. PMID- 17746571 TI - Probability estimates. PMID- 17746572 TI - Earthquake research center siting triggers california tremors. PMID- 17746573 TI - Soviet union suspends plans to divert four rivers. PMID- 17746574 TI - Do California Quakes Portend a Large One?: Far from the San Andreas fault, three lines of evidence hint at a large earthquake striking within the next decade. PMID- 17746575 TI - Washington Embraces Global Earth Sciences: For reasons of science and for reasons of strategy, the funding agencies want to study the earth as an integrated whole. PMID- 17746576 TI - Strong ground motion from the michoacan, Mexico, earthquake. AB - The network of strong motion accelerographs in Mexico includes instruments that were installed, under an international cooperative research program, in sites selected for the high potenial of a large earthquake. The 19 September 1985 earthquake (magnitude 8.1) occurred in a seismic gap where an earthquake was expected. As a result, there is an excellent descripton of the ground motions that caused the disaster. PMID- 17746577 TI - Natural philosophy in the constitution. AB - The natural philosophers who wrote the U.S. social contract held the advancement of science to be the supreme exercise of citizen sovereignty. The rising nation, in the late 19th century, established the seat of that sovereignty in its universities. Today those institutions have come to be regarded as contract research centers at the service of the federal government. Research contracts in support of the proposed Strategic Defense Initiative are pressed on them against the consensus of the scientific community that holds this "Star Wars" enterprise to be technically infeasible. The time has come to reconstruct the relation between the federal government and university science in the spirit of our social contract. PMID- 17746578 TI - Catalytic hydration of terminal alkenes to primary alcohols. AB - Direct catalytic hydration of terminal alkenes to primary alcohols would be an inexpensive route to industrially useful alcohols and a convenient synthetic route for the synthesis of terminal alcohols in general. The reaction between trans- PtHCl(PMe(3))(2) (where Me = CH(3)) and sodium hydroxide in a one-to-one mixture of water and 1-hexene yields a species that, at 60 degrees C and in the presence of the phasetransfer catalyst benzyltriethylammonium chloride, catalyzes selective hydration of 1-hexene to n-hexanol at a rate of 6.9 +/- 0.2 turnovers per hour. Hydration of 1-dodecene to n-dodecanol occurs at a rate of 8.3 +/- 0.4 turnovers per hour at 100 degrees C. Deuterium labeling experiments with trans PtDCl(PMe(3))(2) show that hydration involves reductive elimination of a C-H bond. At low hydroxide concentrations (<8 equivalents), hydration of the water soluble olefin 3-butene-1-ol to 1,4-butanediol exhibited a first-order dependence on hydroxide concentration for loss of catalytic activity. This suggests that hydroxide attacks the coordinated alkene slowly. At high hydroxide concentrations, the rate of catalysis was hydroxide-independent and first order in alkene. Substitution of coordinated water (k(1) = 9.3 +/- 0.5 x 10(-3) liters per mol per second) appears to be limitng under these conditions. PMID- 17746579 TI - Coastal uplift and mortality of intertidal organisms caused by the september 1985 Mexico earthquakes. AB - Coastal uplift associated with the great Mexican earthquake of 19 September 1985 and its principal aftershock produced widespread mortality of intertidal organisms along the coast of the states of Michoacan and Guerrero, Mexico. Measurements of the vertical extent of mortality at ten sites provided estimates of the magnitude of the vertical component of deformation along the coast. Within the affected area, uplift ranged from about 12 centimeters to about 1 meter, and no subsidence was observed. The observations are consistent with models of the tectonic deformation that results from buried slip on a shallow-dipping underthrust fault. PMID- 17746580 TI - Report details human rights in guatemala. PMID- 17746582 TI - Admiral Hopper Talks to AAAS Staff. PMID- 17746581 TI - Museum Project Special Events Draw AAAS Members. PMID- 17746583 TI - Election ballots are in the mail. PMID- 17746584 TI - A painful decision. PMID- 17746585 TI - Fall meetings to focus on science curriculum and international security. PMID- 17746586 TI - Reminder for members. PMID- 17746587 TI - National forum for school science. PMID- 17746588 TI - Neurochemistry: chemical neurobiology. PMID- 17746589 TI - Warnings: read the label. PMID- 17746590 TI - Edentates: the evolution and ecology of armadillos, sloths, and vermilinguas. PMID- 17746592 TI - Some other books of interest: inorganic reactions and methods. PMID- 17746591 TI - Ionic currents in development. PMID- 17746593 TI - Products & materials. PMID- 17746595 TI - Publications Received. PMID- 17746594 TI - The Association's Journals. PMID- 17746596 TI - Meetings & Conferences. PMID- 17746597 TI - Man's Synthetic Future. PMID- 17746598 TI - Association Business. PMID- 17746599 TI - Public Information at Philadelphia. PMID- 17746600 TI - A Report of the Philadelphia Meeting December 26-31, 1951. PMID- 17746601 TI - Reports of Sections and Societies. PMID- 17746603 TI - Future food supply. PMID- 17746604 TI - Academic freedom. PMID- 17746602 TI - Standards for carcinogens. PMID- 17746605 TI - Approval of new drugs. PMID- 17746606 TI - Taxation and energy conservation. PMID- 17746607 TI - Another scientist in congress. PMID- 17746608 TI - Highway salting. PMID- 17746609 TI - Research impact statements. PMID- 17746610 TI - Eruption of soufriere volcano on st. Vincent island, 1971-1972. AB - The Soufriere volcano in St. Vincent erupted from October 1971 to March 1972, as 80 x 10(6) m(3) of basaltic andesite lava was quietly extruded inside the mile wide crater. The eruption was largely subaqueous, taking place in the 180-m-deep crater lake, and resulted in the emergence of a steep-sided island. The mild character of the eruption and the absence of seismic activity stand in direct contrast to the highly explosive character of the eruption of 1902 to 1903. PMID- 17746611 TI - Energy Conservation through Effective Utilization. PMID- 17746612 TI - Psychical research: the incredible in search of credibility. PMID- 17746614 TI - Energy Policy, Phase II. PMID- 17746613 TI - OST Is Dead Long Live STPO. PMID- 17746616 TI - Radio telescope funds at issue. PMID- 17746615 TI - Restored HEW Funds May Be Buried by Regulation. PMID- 17746617 TI - Pesticides: environmentalists seek new victory in a frustrating war. PMID- 17746618 TI - Watergate: Dean's Honor Roll of Enemies Includes Scientists. PMID- 17746619 TI - Mathematical groups. AB - One of the simplest and most useful algebraic structures is the group, study of which dates back to 1830. The concept is not only of mathematical interest, but has found application in fields ranging from quantum mechanics to crystallography. Despite their long history and many uses, groups remain a remote concept to many. Since the accompanying two articles concern advances in group theory and its applications, this short summary of the basic axioms and properties of groups is offered as a convenient primer. PMID- 17746620 TI - Sporadic groups: exceptions, or part of a pattern? PMID- 17746621 TI - Phase changes: a universal theory of critical phenomena. PMID- 17746622 TI - In situ Sampler for Marine Sedimentary Pore Waters: Evidence for Potassium Depletion and Calcium Enrichment. AB - A device for sampling the interstitial waters of deep-sea sediments in situ has been developed and tested. The sampler collects a series of samples over a depth of 1.5 meters in the sediment and thus makes possible the accurate delineation of chemical gradients existing in the pore waters. Samples collected in the North Atlantic indicate that significant gradients of K(+) and Ca(2+) exist in the sediments sampled. Interstitial solutions sampled between Ireland and Cape Cod, Massachusetts, are characterized by the depletion of K(+) and the enrichment of Ca(2+). PMID- 17746623 TI - Heavy elements in surface materials: determination by alpha particle scattering. AB - The backscattering of alpha particles from a radioactive source can be used to determine the amounts of heavy elements such as lead in surface materials. A light, portable instrument has been constructed that can be used as a survey meter for painted surfaces. It has a sensitivity of 0.3 percent by weight in a measurement of a few minutes. PMID- 17746624 TI - Huntite flowstone in carlsbad caverns, new Mexico. AB - Huntite flowstone has recently been discovered in Carlsbad Caverns. This flowstone occurs as a thin, white layer of microcrystals (approximately 1 to 60 micrometers in diameter) which appears buckled and crinkled. The huntite is believed to be precipitating directly from magnesium-rich solutions rather than forming by alteration of preexisting minerals. PMID- 17746625 TI - Suspensions: fluids with fading memories. AB - A sheared liquid suspension whose flow is reversed remembers with various degrees of perfection all earlier configurations of the particles. The memory effects, studied primarily because of their importance in suspension rheology, may be of wider significance. PMID- 17746626 TI - Nitrogen fixation in termites. AB - Nitrogen fixation, measured by the reduction of acetylene to ethylene, was found in workers of the dry-wood termite Kalotermes minor. The soldiers and reproductive castes fixed little or no nitrogen. The fixation rates ranged between 24 and 566 micrograms of nitrogen fixed per month per gram (wet weight) of termite. Nitrogen fixation can be a significant source of nitrogen for these termites. PMID- 17746627 TI - Size of the great white shark (carcharodon). AB - The maximum length of 36.5 feet (11.1 meters) attributed to the white shark (Carcharodon carcharias) by Gunther and others is a mistake. Examination of the jaws and teeth of the specimen referred to by Gunther and comparison with the jaws of white sharks of known length revealed a length of about 17 feet ( approximately 5 meters). The largest white shark reliably measured was a 21-foot (6.4-meter) individual from Cuba. Bites on whale carcasses found off southern Australia suggest that white sharks as long as 25 or 26 feet (7 (1/2) or 8 meters) exist today. The size of extinct Carcharodon has also been grossly exaggerated. Based on a projection of a curve of tooth size of Recent Carcharodon carcharias, the largest fossil Carcharodon were about 43 feet ( approximately 13 meters) long. PMID- 17746629 TI - Perspectives on linear heat transfer. PMID- 17746628 TI - Observation Is Insufficient for Discovering that the Surface of Still Water Is Invariantly Horizontal. AB - Among women college students who did not know that the surface of still water in a bottle is always horizontal, two types of specific task procedures designed to elicit self-discovery of the principle were ineffective. Failure to acquire the concept was reflected in inaccurate responses on the adjustment task and by inability of students to verbalize a correct strategy. PMID- 17746630 TI - Serious contaminant in "ultra pure" grades of sucrose. PMID- 17746631 TI - Long-term effects of perinatal hormone administration. PMID- 17746632 TI - Multichannel analyzer. PMID- 17746633 TI - High-contrast hand refractometer. PMID- 17746634 TI - High-temperature adhesive. PMID- 17746635 TI - Peristaltic pumps. PMID- 17746636 TI - Frequency synthesizer. PMID- 17746637 TI - Literature. PMID- 17746638 TI - Interferometer spectrometer. PMID- 17746639 TI - Televised microsurgery. PMID- 17746641 TI - Westinghouse winners. PMID- 17746640 TI - This Week in SCIENCE. PMID- 17746643 TI - Sciencescope. PMID- 17746642 TI - Molecular probes for rice blast disease. PMID- 17746644 TI - Capping an infected wisdom tooth. PMID- 17746645 TI - Galileo hits a snag. PMID- 17746646 TI - No Citation Analyses Please, We're British. PMID- 17746647 TI - Patriot's Scud Busting Record Is Challenged. PMID- 17746648 TI - Conventional math tests get low marks. PMID- 17746649 TI - Nouvelle cuisine. PMID- 17746650 TI - Presidential digital commitment. PMID- 17746651 TI - New eye on the high seas. PMID- 17746652 TI - ...And lose another. PMID- 17746653 TI - Animal rightists win one.. PMID- 17746654 TI - Correction. AB - Contrary to what we reported, the horned dinosaur Chasmosaurus (Science, 12 April, p. 207) did not have the largest skull of any land animal. Paleontologist Paul Sereno of the University of Chicago says that honor belongs to Triceratops, another member of the family Ceratopsidae. PMID- 17746656 TI - $11.5-million housecleaning. PMID- 17746655 TI - A man's reach must exceed his grasp. PMID- 17746658 TI - Exploring the new material world. PMID- 17746657 TI - Hope for african elephants. PMID- 17746659 TI - One Man's "Night Ride" Through Nitride Country. PMID- 17746660 TI - Buckyballs, hairyballs, dopeyballs. PMID- 17746661 TI - Move over, mendeleyev. PMID- 17746662 TI - Liquid Crystals Meet the Cosmos at APS Meeting A Long Look Into a Liquid Crystal Ball. PMID- 17746663 TI - Liquid Crystals Meet the Cosmos at APS Meeting Atoms for Logic. PMID- 17746664 TI - Liquid Crystals Meet the Cosmos at APS Meeting Shadows in a Sea of Hot Gas. PMID- 17746665 TI - Hot-spot evolution and the global tectonics of venus. AB - The global tectonics of Venus may be dominated by plumes rising from the mantle and impinging on the lithosphere, giving rise to hot spots. Global sea-floor spreading does not take place, but direct convective coupling of mantle flow fields to the lithosphere leads to regional-scale deformation and may allow lithospheric transport on a limited scale. A hot-spot evolutionary sequence comprises (i) a broad domal uplift resulting from a rising mantle plume, (ii) massive partial melting in the plume head and generation of a thickened crust or crustal plateau, (iii) collapse of dynamic topography, and (iv) creep spreading of the crustal plateau. Crust on Venus is produced by gradual vertical differentiation with little recycling rather than by the rapid horizontal creation and consumption characteristic of terrestrial sea-floor spreading. PMID- 17746666 TI - Multiple light-scattering probes of foam structure and dynamics. AB - The structure and dynamics of three-dimensional foams are probed quantitatively by exploiting the strong multiple scattering of light that gives foams their familiar white color. Approximating the propagation of light as a diffusion process, transmission measurements provide a direct probe of the average bubble size. A model for dynamic light scattering is developed that can be used to interpret temporal fluctuations in the intensity of multiply scattered light. The results identify previously unrecognized internal dynamics of the foam bubbles. These light-scattering techniques are direct, noninvasive probes of bulk foams and therefore should find wide use in the study of their properties. PMID- 17746667 TI - Molecular self-assembly of two-terminal, voltammetric microsensors with internal references. AB - Self-assembly of a ferrocenyl thiol and a quinone thiol onto Au microelectrodes forms the basis for a new microsensor concept: a two-terminal, voltammetric microsensor with reference and sensor functions on the same electrode. The detection is based on measurement of the potential difference of current peaks for oxidation and reduction of the reference (ferrocene) and indicator (quinone) in aqueous electrolyte in a two-terminal, linear sweep voltammogram in which a counterelectrode of relatively large surface area is used. The quinone has a half wave potential, E((1/2)), that is pH-sensitive and can be used as a pH indicator; the ferrocene center has an E(1/2) that is a pH-insensitive reference. The key advantages are that such sensors require no separate reference electrode and function as long as current peaks can be located for reference and indicator molecules. PMID- 17746668 TI - Atmospheric Lifetime of CHF2Br, a Proposed Substitute for Halons. AB - The rate coefficients, k(1), for the reaction of OH with CHF(2)Br have been measured using pulsed photolysis and discharge flow techniques at temperatures (T) between 233 and 432 K to be k(1), = (7.4 +/- 1.6) x 10(-13) exp[-(1300 +/- 100)/T] cubic centimeters per molecule per second. The ultraviolet absorption cross sections, sigma, of this molecule between 190 and 280 nanometers were measured at 296 K. The k(1), and sigma values were used in a one-dimensional model to obtain an atmospheric lifetime of approximately 7 years for CHF(2)Br. This lifetime is shorter by approximately factors of 10 and 2 than those for CF(3)Br and CF(2)ClBr, respectively. The ozone depletion potentials of the three compounds will reflect these lifetimes. PMID- 17746669 TI - Partial Melting of the Aliende (CV3) Meteorite: Implications for Origins of Basaltic Meteorites. AB - Eucrites and angrites are distinct types of basaltic meteorites whose origins are poorly known. Experiments in which samples of the Allende (CV3) carbonaceous chondrite were partially melted indicate that partial melts can resemble either eucrites or angrites, depending only on the oxygen fugacity (fo(2)). Melts are eucritic if thefo(2) is below that of the iron-wustite buffer or angritic if above the fo(2) of that buffer. With changing pressure, the graphite-oxygen redox reaction can produce oxygen fugacities that are above or below those of the iron wustite buffer. Therefore, a single, homogeneous, carbonaceous planetoid >110 kilometers in radius could produce melts of drastically different composition, depending on the depth of melting. PMID- 17746670 TI - Hypotheses about Japan. PMID- 17746672 TI - The early Earth. PMID- 17746671 TI - Some other books of interest. PMID- 17746673 TI - Products & materials. PMID- 17746676 TI - THE SECOND PAN-PACIFIC SCIENCE CONGRESS. PMID- 17746674 TI - WORK OF THE NATIONAL RESEARCH COUNCIL. PMID- 17746675 TI - COLLECTING PERIPATUS IN NEW ZEALAND. PMID- 17746677 TI - THE FIRE IN CALIFORNIA. PMID- 17746678 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17746679 TI - APPLES, WORMS, PHILOSOPHERS AND GOATS. PMID- 17746681 TI - ON THE INFLUENCE OF A ROTATING MAGNETIC FIELD UPON GROWTH. PMID- 17746680 TI - PACHYOSTOSIS. PMID- 17746682 TI - WESTERN SOCIETY OF SOIL MANAGEMENT AND PLANT NUTRITION. PMID- 17746683 TI - PACIFIC SLOPE BRANCH AMERICAN ASSOCIATION OF ECONOMIC ENTOMOLOGISTS. PMID- 17746684 TI - THE PACIFIC COAST ENTOMOLOGICAL SOCIETY. PMID- 17746685 TI - PACIFIC DIVISION OF THE PLANT PHYSIOLOGICAL SECTION OF THE BOTANICAL SOCIETY OF AMERICA. PMID- 17746686 TI - PACIFIC FISHERIES SOCIETY. PMID- 17746687 TI - THE WESTERN SOCIETY OF NATURALISTS. PMID- 17746688 TI - THE ECOLOGICAL SOCIETY OF AMERICA. PMID- 17746690 TI - INERTIA AS A POSSIBLE MANIFESTATION OF THE ETHER. PMID- 17746689 TI - PACIFIC BRANCH PALEONTOLOGICAL SOCIETY. PMID- 17746691 TI - THE FAUNA AND FLORA ABOUT COLDSPRING HARBOR, L. I. PMID- 17746692 TI - THE NERNST LAMP. PMID- 17746693 TI - BOTANY AT THE ANNIVERSARY MEETING OF THE AMERICAN ASSOCIATION II. PMID- 17746694 TI - SURVEYS OF THE GATEWAYS TO ALASKA. PMID- 17746695 TI - NOTES ON INORGANIC CHEMISTRY. PMID- 17746696 TI - BOTANICAL NOTES. PMID- 17746698 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17746697 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17746699 TI - PERIDINIUM AND THE 'RED WATER' IN NARRAGANSETT BAY. PMID- 17746700 TI - DISCUSSION AND CORRESPONDENCE. PMID- 17746701 TI - ZOOLOGICAL BIBLIOGRAPHY. PMID- 17746703 TI - THE NERNST LIGHT. PMID- 17746702 TI - THE DAY OF THE WEEK. PMID- 17746704 TI - NORTHERN ROCKY MOUNTAIN GLACIERS. PMID- 17746706 TI - THE AMERICAN WHALE-FISHERY, 1877-1886. PMID- 17746705 TI - SCIENTIFIC JOURNALS. PMID- 17746707 TI - ICE AND ICEBERGS. PMID- 17746708 TI - MULLER'S SCIENCE OF LANGUAGE. PMID- 17746709 TI - Letters to the editor. PMID- 17746710 TI - Letters to the editor. PMID- 17746711 TI - Animal care in the laboratory: who should regulate it? PMID- 17746712 TI - Letters to the editor. PMID- 17746714 TI - The tea leaves or the record? PMID- 17746715 TI - Studies of Alloys by X-ray Absorption Spectroscopy. PMID- 17746713 TI - Paleomagnetism and evolution. PMID- 17746717 TI - Cultural patterns in narrative. PMID- 17746716 TI - The search for extraterrestrial life. PMID- 17746718 TI - Pittsburgh: The Rocky Road to Academic Excellence (III). PMID- 17746719 TI - Food and drug administration: test for leadership vaccine. PMID- 17746720 TI - Weather modification: senate bills stir agency rivalries. PMID- 17746721 TI - Pasteur institute scientists demand sweeping reform. PMID- 17746722 TI - Lithium-drifted germanium detectors: applications to neutron-activation analysis. AB - Lithium-drifted germanium detectors for high-resolution gamma-ray spectroscopy reduce the need for wet chemistry in neutron-activation analysis. Problems in fields as diverse as geochemistry and the history of 15th-century printing have proved susceptible to this analytic technique. PMID- 17746724 TI - Imidonitrogen in chlorella "polyphosphate". AB - "Polyphosphate" and fragments isolated from acid hydrolysis of polyphosphate have an infrared absorption band at 1400 cm(-1), which is characteristic of imidodiphosphate linkages. Complete hydrolysis of purified "polyphosphate" releases 1 to 2 moles of phosphate per mole of ammonia. The polymer must contain subunits which are cyclic and which contain both imidodiphosphate linkages and phosphate anhydride linkages. PMID- 17746723 TI - Rubidium-strontium age of the bosumtwi crater area, ghana, compared with the age of the ivory coast tektites. AB - Rocks from the vicinity of Bosumtwi crater, Ghana, and a repre-sentative collection of Ivory Coast tektites have been analyzed mass spectrometrically for rubidium, strontium, and strontium isotopic composition. The data from the rocks of the crater area yield an age of 1.97 x 10(9) years (lambda(gb) = 1.47 chi 10( 11) year(-1)). The data for the Ivory Coast tektites fall on this isochron. This identity of age values for the Ivory Coast tektites and the Birrimian basement rocks of West Africa strongly supports the hypothesis of terrestrial formation for these tektites. The evidence available at present suggests that the Ivory Coast tektites are most probably the fusion products of meteoritic impact at the Bosumtwi crater site. PMID- 17746725 TI - Encephalitogenic activity of bovine basic proteins. AB - Two basic proteins isolated from bovine white matter in connection with a study of the protein-bound phosphoinositides of central nervous system tisstue have been tested for encephalitogenic activity. The biological activity of these proteins, which is equivalent to that of basic encephalitogenic proteins isolated in other laboratories, suggested that they are identical. PMID- 17746726 TI - Hemagglutination by fava bean extract inhibited by simple sugars. AB - Hemagglutination by extract of fava bean was inhibited by 5-percent d-glucose, d fructose, or maltose, but not by 5-percent d-galactose or lactose. Failure to inhibit seems to reflect the presence of a hydroxyl group at the carbon No. 4 position. Hemagglutination was enhanced by dextran of high molecular weight, but not by dextran of low molecular weight. The finding supports the hypothesis that large molecular size explains the enhancement by gum acacia of hemagglutination by fava bean. PMID- 17746727 TI - Intracellular localization of growth hormones in plants. AB - Autoradiographic studies of Allium cernuum and Vicia faba root-tip cells treated with indoleacetic acidmethyl-C(14) or 2,4-dichlorophenoxyacetic acid-carboxyl C(14) revealed nuclear and cytoplasmic labeling of the cells. The cytoplasmic labeling decreased with time after the removal of the labeled auxin, but nuclear and chromosomal labeling was retained for at least 120 hours. PMID- 17746728 TI - Phenylalanine: Transplacental centrations in Rhesus Monkeys. AB - Arbino acids are actively transported across the mammalian placenta, crncentrations in fetal blood being higher than those in the maternal circu Elevated concentrations of phenylalanine were induced by dietarv means blood of pregnant rhesus monkeys, and the active transport mechanism vident at both normal and elevated concentrations. A normal placental may thus magnify a maternal biochemical abnormality and produce a profound disturbance in the fetus. PMID- 17746729 TI - Catecholamine Concentrations: Changes in Plasma of Rats during Estrous Cycle and Pregnancy. AB - Concentrations of norepinephrine in plasma of rats during estrus and pregnancy were significantly lower than during diestrus. Epinephrlne concentrations in the plasma were significantly higher in both estrous and diestrous females than in males. PMID- 17746730 TI - Environmental Control of Ovarian Development in Mosquitoes of the Culex pipiens Complex. AB - Gonotrophic dissociation, a condition in which the ovaries remain undeveloped in female mosquitoes that have taken a full blood meal, occurs in Culex pipiens L., when incubated at low temperature (10 degrees to 15 degrees C) with short photoperiod and held at low temperature after feeding. Gonotrophic dissociation occurred sporadically in Culex quinquefasciatus Say after conditioning by low temperature, irrespective of photoperiod. Two major considerations are posed: first, the importance of gonotrophic dissociation to hibernation potential; and, second, the potential of a hibernating female mosquito to serve as a virus reservoir. PMID- 17746731 TI - Rh factor: prevention of isoimmunization and clinical trial on mothers. AB - The results on the use of gammaG-immunoglobulin to Rh factor for the prevention of active immunization of Rh-negative mothers at risk appear most promising. One hundred and seven mothers in the clinical trial have been followed for periods of about 6 months to 1(1/2)12 years after delivery. Of these, 48 were treated mothers who received 5 ml gammaG-immunoglobulin to Rh, and 59 were untreated mothers. Of the 48 treated mothers none are actively immunized; seven of the 59 control mothers have become actively immunized to Rh. PMID- 17746732 TI - Visual-cliff preference by infant rats: effects of rearing and test conditions. AB - In monocular tests, normally reared infant rats, aged 21 to 22 days, fail to show a side preference on the visual-cliff apparatus. Rats of the same age, but reared in an "enriched" environment, prefer the shallow side of the apparatus. In binocular tests, even normally reared animals prefer the shallow side, although experimentally reared animals show a stronger preference. The results appear to reopen the question of what cues are employed on the visual cliff. PMID- 17746733 TI - Slant perception and shape constancy in infants. AB - Three experiments investigated shape constancy in human infants between 50 and 60 days of age. The first showed that such infants possess some capacity for shape constancy. The second confirmed this finding and showed that the capacity is not attained by correlation of perceived projective shape with perceived orientation. PMID- 17746734 TI - An examination of "transfer of learning" by nucleic Acid. AB - Nucleic acid extracted from brains of trained animals and injected intraperitoneally into naive animals produced no "transfer of learning" effect on several tasks under many conditions. P(325)-Labeled RNA was not found in the brain after intraperitoneal administration. Even intraventricular injections of nucleic acid produced no "transfer" effect. PMID- 17746735 TI - Imagery: effect of a concealed figure in a stimulus. AB - A concealed figure formed by the contours of a perceptually dominant figure influenced the content of viewers' subsequent imagery, although in describing the stimulus they showed no awareness of the concealed figure even after several exposures. PMID- 17746737 TI - Pain: one mystery solved. PMID- 17746736 TI - Computer stereography. PMID- 17746738 TI - Visual excitation of blood clotting. PMID- 17746739 TI - A report of the fourth berkeley meeting. PMID- 17746741 TI - Society for industrial and applied mathematics (a5). PMID- 17746740 TI - Behavior, brain, and biochemistry. PMID- 17746742 TI - American mathematical society (A1). PMID- 17746743 TI - Mathematics (a). PMID- 17746744 TI - Chemistry (C). PMID- 17746745 TI - Physics (B). PMID- 17746746 TI - Recent developments in the study of energy transfer. PMID- 17746747 TI - Geology and geography (e). PMID- 17746748 TI - Astronomy (d). PMID- 17746749 TI - Zoological sciences (f). PMID- 17746750 TI - Tertiary provincial and immigrant terrestrial vertebrates. PMID- 17746751 TI - Ecological Society of America (FG3). PMID- 17746752 TI - Herpetologists' league (f4). PMID- 17746753 TI - Animal behavior society (f3). PMID- 17746755 TI - Botanical sciences (g). PMID- 17746754 TI - American fisheries society (f1). PMID- 17746756 TI - Psychology (I). PMID- 17746758 TI - American economic association (k1). PMID- 17746757 TI - Anthropology (h). PMID- 17746759 TI - Social and economic sciences (k). PMID- 17746760 TI - American political science association (k2). PMID- 17746761 TI - National institute of social and behavioral science (k6). PMID- 17746762 TI - Society for the scientific study of religion (k8). PMID- 17746763 TI - Society for general systems research (l3). PMID- 17746764 TI - History and philosophy of science (L). PMID- 17746765 TI - Medical sciences (N). PMID- 17746766 TI - Engineering (m). PMID- 17746767 TI - Dentistry (nd). PMID- 17746768 TI - American physiological society (n3). PMID- 17746769 TI - Pharmaceutical sciences (np). PMID- 17746770 TI - International science teaching. PMID- 17746771 TI - Education (q). PMID- 17746773 TI - Agriculture (0). PMID- 17746772 TI - Industrial science (p). PMID- 17746774 TI - Piaget's Research and Its Implications for Science Education. PMID- 17746776 TI - Education (q). PMID- 17746775 TI - National association of biology teachers (q8). PMID- 17746777 TI - Current Issues in Communication of Science II: The Scientific Meeting and Related Publications. PMID- 17746778 TI - State of the art and the prospects for data gathering, storage, transformation, and retrieval. PMID- 17746779 TI - Society of technical writers and publishers (t2). PMID- 17746780 TI - Statistics (u). PMID- 17746781 TI - Biometric societv, eastern north american region (u3). PMID- 17746782 TI - Science in general (x). PMID- 17746783 TI - Forthcoming events. PMID- 17746784 TI - Science in china. PMID- 17746785 TI - Science in china. PMID- 17746786 TI - Funding basic research: continued. PMID- 17746787 TI - Keratinocytes and the danger model. PMID- 17746788 TI - Response: Beta sheets and spider silk. PMID- 17746789 TI - THE MAN OF SCIENCE AND THE PUBLIC. PMID- 17746790 TI - OBSERVATIONS ON THE SOLAR ECLIPSE MADE BY THE CROCKER EXPEDITIONOF THE LICK OBSERVATORY. PMID- 17746791 TI - BROWN ROT OF SOLANACEA ON RICINUS. PMID- 17746792 TI - CELLULOID LANTERN-SLIDES. PMID- 17746793 TI - WASHING MICROSCOPIC ORGANISMS. PMID- 17746794 TI - AN OPTICAL ILLUSION WITH FATAL CONSEQUENCES. PMID- 17746795 TI - THE RYDBERG UNIVERSAL CONSTANT No. PMID- 17746796 TI - MOISTURE RATIO. PMID- 17746797 TI - THE IOWA ACADEMY OF SCIENCE. II. PMID- 17746798 TI - COMMENT AND CRITICISM. PMID- 17746799 TI - THE AMERICAN SCHOOL OF CLASSICAL STUDIES AT ATHENS. PMID- 17746800 TI - LONDON LETTER. PMID- 17746801 TI - GEOGRAPHICAL NOTES. PMID- 17746802 TI - A sensitive wind-vane. PMID- 17746804 TI - The rudimentary metacarpals of bison. PMID- 17746803 TI - The Bellville meteor. PMID- 17746805 TI - On tiptoe. PMID- 17746806 TI - The power of a voter. PMID- 17746807 TI - Lebensraum. PMID- 17746808 TI - Discovery to patent to license. PMID- 17746809 TI - Protesting mathematicians. PMID- 17746810 TI - A new base for political support of academic science. PMID- 17746811 TI - Variable galaxies. PMID- 17746813 TI - And CBW. PMID- 17746812 TI - Food production in prehistoric europe. PMID- 17746814 TI - Nuclear weapons . . PMID- 17746815 TI - Space: Europe Makes Move toward Setting Up a Central Organization. PMID- 17746816 TI - Infrasound at long range from saturn v, 1967. AB - Two distinct groups of infrasonic waves from Saturn V, 1967, were recorded at Palisades, New York, 1485 kilometers from the launch site. The first group, of 10 minute duration, began about 70 minutes after launch time; the second, having more than twice the amplitude and a duration of 9 minutes, commenced 81 minutes after launch time. From information on the Saturn V trajectory and analysis of recorded data, it is established that the first group represents sound emitted either by the first stage reentry or by the second stage when its elevation was above 120 kilometers. The second, more intense wave group represents the sound from the powered first stage. A reversal of signal occurs because the rocket outran its own sound. Fourier analyses indicate that the energy extends to relatively long periods-10 seconds for the first stage and 7 seconds for the second. Trapping of sound in the upper atmospheric sound channel can be the cause of the separation of the signal into two distinct groups. PMID- 17746817 TI - Attenuation of low-frequency sound in freshwater. AB - Lake Superior was chosen as an experimental site to compare sound absorption of freshwater with the results of absorption measurements in seawater. The relaxation-like absorption at 1 kilohertz occurring in seawater is also present in freshwater. A relaxation related to the structural characteristics rather than to the salt content of water may be responsible for the anomalous absorption. PMID- 17746818 TI - Sea Levels during the Past 35,000 Years. AB - A sea-level curve of the past 35,000 years for the Atlantic continental shelf of the United States is based on more than 80 radiocarbon dates, 15 of which are older than 15,000 years. Materials include shallow-water mollusks, oolites, coralline algae, beachrock, and salt-marsh peat. Sea level 30,000 to 35,000 years ago was near the present one. Subsequent glacier growth lowered sea level to about -130 meters 16,000 years ago. Holocene transgression probably began about 14,000 years ago, and continued rapidly to about 7000 years ago. Dates from most shelves of the world agree with this curve, suggesting that it is approximately the eustatic curve for the period. PMID- 17746819 TI - Manganese nodules in lake michigan. AB - Manganese nodules containing up to 22 percent manganese oxide were found in Green Bay and the western and northern parts of Lake Michigan. The chemical composition of these nodules resembles that of shallow-water lacustrine and marine nodules. The manganese content of interstitial water is in some places enriched as much as 4000 times over that of lake water. PMID- 17746820 TI - Weddellite in a marine gastropod and in antarctic sediments. AB - The calcium oxalate dihydrate mineral, weddellite, has been identified in a microarchitectural component of the gizzard plates from the deepwater gastropod Scaphander cylindrellus. This is the first indication of nonpathologic precipitation of this mineral by an animal species. A new occurrence of weddellite in sediments from the Weddell Sea, Antarctica, is also reported, lending support to the earlier interpretation that the mineral is an authigenic constituent of the sediments in this area. PMID- 17746821 TI - Galapagos Flora: Fernandina (Narborough) Caldera before Recent Volcanic Event. AB - A collection of 25 flowering plants was made from the inner cone of Fernandina crater. The distribution, relationships and dispersal mechanisms of these species are considered in the light of recent physical changes resulting from volcanic activity. PMID- 17746822 TI - Chemical potential of water from measurements of optic axial angle of zeolites. AB - Values of the uncorrected optic axial angle (2H(alpha)) of a crystal of the calcium zeolite stellerite (CaAl(2)Si(7)O(l8) . 7H(2)0) immersed in calcium chloride solutions of known activity of water (a(w)) are directly proportional to log a(w). A general relationship between the chemical potential of water in the crystal and the optic axial angle is obeyed. PMID- 17746823 TI - Neolithic economic autonomy and social distance. AB - The following hypothesis was tested in the prehistoric Mogollon culture area of the American Southwest: increasing dependence on agriculture leads to increasing social distance between the minimal economic units needed to make agriculture a successful economic base. Both variables covaried positively. As dependence on agriculture increased, villages became more endogamous. PMID- 17746824 TI - Aaas annual meeting. PMID- 17746826 TI - Mathematics (a). PMID- 17746825 TI - Aaas committee symposia. PMID- 17746827 TI - Astronomy (d). PMID- 17746828 TI - Chemistry (C). PMID- 17746829 TI - Physics (B). PMID- 17746830 TI - Geography and geology. PMID- 17746831 TI - Zoological sciences (f). PMID- 17746832 TI - Botanical sciences (g). PMID- 17746833 TI - Biological sciences (FG). PMID- 17746834 TI - Anthropology (h). PMID- 17746835 TI - Psychology (I). PMID- 17746836 TI - Social and economic sciences (k). PMID- 17746837 TI - History and philosophy of science. PMID- 17746838 TI - Medical sciences (N). PMID- 17746839 TI - Engineering (m). PMID- 17746840 TI - Agriculture (o). PMID- 17746841 TI - DENTISTRY (Nd). PMID- 17746842 TI - Education (q). PMID- 17746843 TI - Industrial science (p). PMID- 17746844 TI - General sciences (x). PMID- 17746845 TI - Statistics (u). PMID- 17746846 TI - The Scientists Must Speak Up. PMID- 17746847 TI - Meetings & Conferences. PMID- 17746848 TI - Byron Cummings, Archeologist and Explorer. PMID- 17746849 TI - Miscellaneous Publications. PMID- 17746850 TI - "Big Business Takes Over Research". PMID- 17746851 TI - A Comment on Scientific Writing. PMID- 17746853 TI - THE WORK OF THE COAST AND GEODETIC SURVEY. PMID- 17746854 TI - RECENT DEVELOPMENTS IN THE STUDY OF RADIOACTIVE SUBSTANCES. PMID- 17746852 TI - Depiction of the Lecithin Molecule. PMID- 17746855 TI - THE TWENTY-FIFTH ANNIVERSARY OF DOCTOR VICTOR C. VAUGHAN'S GRADUATION. PMID- 17746857 TI - THE SPECIFIC HEAT OF MERCURY. PMID- 17746856 TI - ANTARCTICA. PMID- 17746858 TI - THE PROPOSED BIOLOGICAL LABORATORY AT THE TORTUGAS. PMID- 17746859 TI - ABBREVIATIONS OF NEW MEXICO. PMID- 17746860 TI - THE MEDICAL RESEARCH LABORATORY OF COLORADO COLLEGE. PMID- 17746862 TI - TABLETTES ZOOLOGIQUES. PMID- 17746861 TI - UNUSUAL ABUNDANCE OF A MYRIAPOD, PARAJULUS PENNSYLVANICUS (BRANDT). PMID- 17746864 TI - UNIVERSAITY AND EDUCATIONAL NEWS. PMID- 17746863 TI - STEGOCERAS AND STEREOCEPHALUS. PMID- 17746865 TI - Sulfur dioxide emissions. PMID- 17746866 TI - High-technology agriculture. PMID- 17746867 TI - Nitropyrenes. PMID- 17746868 TI - Infrastructure. PMID- 17746869 TI - The computer issue. PMID- 17746870 TI - An approach to complexity: numerical computations. AB - The use of supercomputers and modern color-imaging techniques for numerical computation is beginning to fulfill von Neumann's vision that digital computers would become the most appropriate tool for solving nonlinear partial differential equations. An example of this approach, a model for the gas flow in the vicinity of a black hole, is described. From such calculations comes a realization that the multidimensional, dynamic solutions of nonlinear partial differential equations can exhibit complex behavior compared to what one normally encounters in analytic solutions. This complexity includes small-scale chaotic structure and large-scale persistently ordered structure. Computational methodology and the aesthetics that derive from it are discussed. PMID- 17746871 TI - New approaches in economic analysis. AB - The level of detail of economic models has until recently been limited by the availability of computational capability. At present, the constraint is the systematic compilation of detailed and comprehensive economic and technical data and the ability to manipulate them. The effective use of enhanced data processing capabilities will have to proceed hand in hand with a concerted effort to develop the economic database and with the shift from analytic approaches based on aggregative data to those that can take advantage of detailed information. PMID- 17746872 TI - Computers in production agriculture. AB - Modern production agriculture in the United States is becoming so complex and sophisticated that computers may soon be an essential tool of successful farm operation and management. Farmers are vigorously seeking information on relevant computer technology and using it as rapidly as economics and availability permit. Their demand for this technology is, however, price-sensitive under current economic conditions. The agricultural research and development system has a long way to go to provide the large integrated software and hardware packages including simulators and expert systems interfaced with monitoring and control devices-needed to help American farmers retain their competitive edge. PMID- 17746873 TI - Computer applications in the humanities. AB - The earliest and still most prevalent use of computers in the humanities is the compilation of concordances, rationalized vocabulary lists for literary works. The residue of these efforts has created the potential for extensive databases of natural-language text for a wide range of studies and for instruction. As yet, however, computer-aided instruction has focused on mechanical skills, like spelling and grammar. With rapid advances in storage (like videodisks) and in communications between computers, humanists are finding a challengingly altered environment in which to study and teach. PMID- 17746874 TI - Personal computers on campus. AB - Colleges and universities are becoming test beds for the much-heralded "information society" as they incorporate a new series of information technologies. These include on-line databases, magnetic and optical data storage, digital telecommunications, computer networks, and, most visibly and dramatically, personal computers. The transition is presenting administrators and faculty with major challenges, however. This article discusses some of the issues involved, including access to computers and to computer networking, managing the transition, and the educational uses of personal computers. A final section discusses efforts at Massachusetts Institute of Technology, Brown University, and Camegie-Mellon University to shape a new-generation personal computer, the so called "scholar's workstation." PMID- 17746875 TI - Intelligent tutoring systems. AB - Cognitive psychology, artificial intelligence, and computer technology have advanced to the point where it is feasible to build computer systems that are as effective as intelligent human tutors. Computer tutors based on a set of pedagogical principles derived from the ACT theory of cognition have been developed for teaching students to do proofs in geometry and to write computer programs in the language LISP. PMID- 17746876 TI - Multis: a new class of multiprocessor computers. AB - Multis are a new class of computers based on multiple microprocessors. The small size, low cost, and high performance of microprocessors allow the design and construction of computer structures that offer significant advantages in manufacture, price-performance ratio, and reliability over traditional computer families. Currently, commercial multis consist of 4 to 28 modules, which include microprocessors, common memories, and input-output devices, all of which communicate through a single set of wires called a bus. Adding microprocessors together increases the performance of multis in direct proportion to their price and allows multis to offer a performance range that spans that of small minicomputers to mainframe computers. Multis are commercially available for applications ranging from real-time industrial control to transaction processing. Traditional batch, time-sharing, and transaction systems process a number of independent jobs that can be distributed among the microprocessors of a multi with a resulting increased throughput (number of jobs completed per unit of time). Many scientific applications (such as the solving of partial differential equations) and engineering applications (such as the checking of integrated circuit designs) are speeded up by this parallel computation; thus, multis produce results at supercomputer speed but at a fraction of the cost. Multis are likely to be the basis for the next, the fifth, generation of computers-a generation based on parallel processing. PMID- 17746877 TI - Workstations in science. AB - Recent advances in microprocessor technology are making a new generation of personal computers feasible and affordable. These computers, called "workstations," can be connected with other workstations, with mainframe computers, with supercomputers, and with remote networks. Workstations provide the graphical interface to supercomputers and can run applications that formerly required the use of mainframe computers. Emerging standards for communications, graphics, databases, numerical algorithms, and languages allow workstations to share programs with various types of computers, including mainframe and personal computers. PMID- 17746878 TI - Security Problems Plague Scientific Meeting: Twenty percent of the papers were blocked by the Defense Department from open presentation; many were shifted to restricted sessions. PMID- 17746879 TI - Europe Tries Cooperation on Military R&D: Economic and technical incentives, coupled with pressure from the United States, are forcing European governments to explore new links. PMID- 17746880 TI - Deficit woes spur drive to kill synfuels. PMID- 17746881 TI - Comings and goings. PMID- 17746883 TI - Mixed signals on stanford biotech patent. PMID- 17746882 TI - U.s. Tops soviets in key weapons technology. PMID- 17746884 TI - Must "Hard Problems" Be Hard?: Computer scientists have new hope that they will be able to learn how hard problems really are. PMID- 17746885 TI - Synchrotron Radiation Takes Over at Orsay: Once a small, piggyback operation, the LURE laboratory now has exclusive use of all Orsay accelerators and is building a new one. PMID- 17746886 TI - Occupational inequalities: sex segregation in the workplace. PMID- 17746887 TI - Nonlinear dynamics: statistical physics and chaos in fusion plasmas. PMID- 17746888 TI - Some other books of interest: dinoflagellates. PMID- 17746889 TI - Some other books of interest: handbook of squirrel monkey research. PMID- 17746890 TI - Quaternary environments: qnaternary stratigraphy of Canada. PMID- 17746891 TI - Storage and remobilization of suspended sediment in the lower Amazon river of Brazil. AB - In the lower Amazon River, suspended sediment is stored during rising stages of the river and resuspended during falling river stages. The storage and resuspension in the reach are related to the mean slope of the flood wave on the river surface; this slope is smaller during rising river stages than during falling stages. The pattern of storage and resuspension damps out the extreme values of high and low sediment discharge and tends to keep them near the mean value between 3.0 x 10(6) and 3.5 x 10(6) metric tons per day. Mean annual discharge of suspended sediment in the lower Amazon is between 1.1 x 10(9) and 1.3 x 10(9) metric tons per year. PMID- 17746892 TI - Products and materials. PMID- 17746893 TI - This week in science. PMID- 17746894 TI - Frontiers in plant biology. PMID- 17746895 TI - Transmutation of high-level nuclear waste. PMID- 17746896 TI - The future of universities. PMID- 17746897 TI - In reply: sexism and hypocrisy. PMID- 17746898 TI - Sexism and hypocrisy. PMID- 17746900 TI - Erratum. AB - In Bernard M. Oliver's letter "Metrification oversold?" (2 Nov., p. 611), William (Ed) Deming's name was misspelled. PMID- 17746899 TI - Proton microprobe development. PMID- 17746902 TI - In reply: proton microprobe development. PMID- 17746901 TI - Indirect costs and merit review. PMID- 17746903 TI - Soviet Nuclear Testing: The Republics Say No: Protesters in Kazakhstan and Boris Yeltsin's government in the Russian republic are giving weapons testers a hard time. PMID- 17746905 TI - Who takes science? PMID- 17746904 TI - National science, technology medalists named. PMID- 17746906 TI - Hubble sees birth of a star. PMID- 17746907 TI - German court rules on physics surveys. PMID- 17746908 TI - Playing chicken with mount st. Helens. PMID- 17746909 TI - Umbilical blood as marrow substitute. PMID- 17746910 TI - Dreary days for british brains. PMID- 17746911 TI - New life for german egyptology. PMID- 17746912 TI - Nitrogen-Fixing Bacteria Find New Partners: Researchers have induced nitrogen fixing rhizobial bacteria to form root nodules on nonlegumes, including rice. PMID- 17746913 TI - The name of the rose, or hunting for a plant database. PMID- 17746914 TI - Venus is looking too pristine. PMID- 17746915 TI - Phase change and the regulation of shoot morphogenesis in plants. AB - The shoot system of higher plants passes through several different phases during its development. Each of these phases is characterized by a unique set of morphological and physiological attributes. The intermediate character of the structures produced during phase changes and the phenotypes of mutations that affect this process demonstrate that these phases are specified by independently regulated, overlapping developmental programs. Transitions between phases appear to be initiated by factors extrinsic to the shoot apical meristem; the ability of the shoot to respond to such factors and to remain in a particular phase of development is regulated by factors intrinsic to the meristem. The possibility that developmental phases are maintained by epigenetic cell states and the role of DNA methylation in this process are discussed. PMID- 17746916 TI - Genetic Control of Flower Development by Homeotic Genes in Antirrhinum majus. AB - Homeotic mutants have been useful for the study of animal development. Such mutants are also known in plants. The isolation and molecular analysis of several homeotic genes in Antirrhinum majus provide insights into the underlying molecular regulatory mechanisms of flower development. A model is presented of how the characteristic sequential pattern of developing organs, comprising the flower, is established in the process of morphogenesis. PMID- 17746917 TI - The Texas cytoplasm of maize: cytoplasmic male sterility and disease susceptibility. AB - The Texas cytoplasm of maize carries two cytoplasmically inherited traits, male sterility and disease susceptibility, which have been of great interest both for basic research and plant breeding. The two traits are inseparable and are associated with an unusual mitochondrial gene, T-urf13, which encodes a 13 kilodalton polypeptide (URF13). An interaction between fungal toxins and URF13, which results in permeabilization of the inner mitochondrial membrane, accounts for the specific susceptibility to the fungal pathogens. PMID- 17746918 TI - Developmental biology of a plant-prokaryote symbiosis: the legume root nodule. AB - The development of nitrogen fixing root nodules on the roots of leguminous plants is induced by soil bacteria (for example, from the genus Rhizobium). The formation of this plant organ involves specific activation of genes in both plant and bacterium. Analysis of these genes gives insight into the way in which plant and bacterium succeed in coordinating plant development. PMID- 17746919 TI - Molecular chaperones: the plant connection. AB - Molecular chaperones are a family of unrelated proteins found in all types of cell. They mediate the correct assembly of other polypeptides, but are not components of the mature assembled structures. Chaperones function by binding specifically to interactive protein surfaces that are exposed transiently during many cellular processes and so prevent them from undergoing incorrect interactions that might produce nonfunctional structures. The concept of molecular chaperones originated largely from studies of the chloroplast enzyme rubisco, which fixes carbon dioxide in plant photosynthesis; the function of chaperones forces a rethinking of the principle of protein self-assembly. PMID- 17746920 TI - The Cauliflower Mosaic Virus 35S Promoter: Combinatorial Regulation of Transcription in Plants. AB - Appropriate regulation of transcription in higher plants requires specific cis elements in the regulatory regions of genes and their corresponding trans-acting proteins. Analysis of the cauliflower mosaic virus (CaMV) 35S promoter has contributed to the understanding of transcriptional regulatory mechanisms. The intact 35S promoter confers constitutive expression upon heterologous genes in most plants. Dissection into subdomains that are able to confer tissue-specific gene expression has demonstrated that the promoter has a modular organization. When selected subdomains are combined, they confer expression not detected from the isolated subdomains, suggesting that synergistic interactions occur among cis elements. The expression patterns conferred by specific combinations of 35S subdomains differ in tobacco and petunia. This indicates that a combinatorial code of cisregulatory elements may be interpreted differently in different species. PMID- 17746922 TI - Ridge spreading, subduction, and sea level fluctuations. AB - A numerical model of mantle convection shows that sea level fluctuations are not simply associated with temporal changes in ocean c plate spreading. In the dynamic model, sea level rises rapidly and then falls toward a steady value (but one still higher than the initial) following increased ridge spreading; this time dependence results from profound changes in the deep thermal structure under ocean and continent. The use of past variations in oceanic spreading to infer sea level fluctuations is called into question. With more realistic models and better continental stratigraphy, constraints may be placed on the viscosity structure of the mantle. PMID- 17746921 TI - Effects of climatic warming on lakes of the central boreal forest. AB - Twenty years of climatic, hydrologic, and ecological records for the Experimental Lakes Area of northwestern Ontario show that air and lake temperatures have increased by 2 degrees C and the length of the ice-free season has increased by 3 weeks. Higher than normal evaporation and lower than average precipitation have decreased rates of water renewal in lakes. Concentrations of most chemicals have increased in both lakes and streams because of decreased water renewal and forest fires in the catchments. In Lake 239, populations and diversity of phytoplankton also increased, but primary production showed no consistent trend. Increased wind velocities, increased transparency, and increased exposure to wind of lakes in burned catchments caused thermoclines to deepen. As a result, summer habitats for cold stenothermic organisms like lake trout and opposum shrimp decreased. Our observations may provide a preview of the effects of increased greenhouse warming on boreal lakes. PMID- 17746923 TI - Ice nucleation by alcohols arranged in monolayers at the surface of water drops. AB - Monolayers of aliphatic long-chain alcohols induced nucleation of ice at temperatures approaching 0 degrees C, in contrast with water-soluble alcohols, which are effective antifreeze agents. The corresponding fatty acids, or alcohols with bulky hydrophobic groups, induce freezing at temperatures as much as 12 degrees C lower. The freezing point induced by the amphiphilic alcohols was sensitive not only to surface area per molecule but, for the aliphatic series (C(n)H(2n + 1)OH), to chain length and parity. The freezing point for chains with n odd reached an asymptotic temperature of 0 degrees C for an upper value of n = 31; for n even the freezing point reached a plateau of -8 degrees C for n in the upper range of 22 to 30. The higher freezing point induced by the aliphatic alcohols is due to formation of ordered clusters in the uncompressed state as detected by grazing incidence synchrotron x-ray diffraction measurements. The diffraction data indicate a close lattice match with the ab layer of hexagonal ice. PMID- 17746924 TI - Chiral symmetry breaking in sodium chlorate crystallizaton. AB - Sodium chlorate (NaClO(3)) crystals are optically active although the molecules of the compound are not chiral. When crystallized from an aqueous solution while the solution is not stirred, statistically equal numbers of levo (L) and dextro (D) NaClO(3) crystals were found. When the solution was stirred, however, almost all of the NaClO(3) crystals (99.7 percent) in a particular sample had the same chirality, either levo or dextro. This result represents an experimental demonstration of chiral symmetry breaking or total spontaneous resolution on a macroscopic level brought about by autocatalysis and competition between L- and D crystals. PMID- 17746925 TI - Salicylic Acid: a likely endogenous signal in the resistance response of tobacco to viral infection. AB - Some cultivars of tobacco are resistant to tobacco mosaic virus (TMV) and synthesize pathogenesis-related (PR) proteins upon infection. In a search for the signal or signals that induce resistance or PR genes, it was found that the endogenous salicylic acid levels in resistant, but not susceptible, cultivars increased at least 20-fold in infected leaves and 5-fold in uninfected leaves after TMV inoculation. Induction of PRl genes paralleled the rise in salicylic acid levels. Since earlier work has demonstrated that treatment with exogenous salicylic acid induces PR genes and resistance, these findings suggest that salicylic acid functions as the natural transduction signal. PMID- 17746926 TI - Increase in salicylic Acid at the onset of systemic acquired resistance in cucumber. AB - In an effort to identify the signal compound that mediates systemic acquired resistance (SAR), changes in the content of phloem sap were monitored in cucumber plants inoculated with either tobacco necrosis virus or the fungal pathogen Colletotrichum lagenarium. The concentration of a fluorescent metabolite was observed to increase transiently after inoculation, with a peak reached before SAR was detected. The compound was purified and identified by gas chromatography mass spectrometry as salicylic acid, a known exogenous inducer of resistance. The data suggest that salicylic acid could function as the endogenous signal in the transmission of SAR in cucumber. PMID- 17746927 TI - The Impossible Science. An Institutional Analysis of American Sociology. Stephen Park Turner and Jonathan H. Turner. Sage, Newbury Park, CA, 1990. 222 pp., illus. $36; paper, $17.95. Sage Library of Social Research, vol. 181. PMID- 17746928 TI - Packrat Middens. The Last 40,000 Years of Biotic Change. Julio L. Betancourt, Thomas R. Van Devender, and Paul S. Martin, Eds. University of Arizona Press, Tucson, 1990. viii, 469 pp., illus. $55. PMID- 17746929 TI - Particle Physics and Inflationary Cosmology. Andrei Linde. Harwood, New York, 1990. xviii, 362 pp., illus. $60; paper, $29. Contemporary Concepts in Physics, vol. 5. Translated from the Russian by Marc Damashek. PMID- 17746930 TI - Molecular Systematics. David M. Hillis and Craig Moritz, Eds. Sinauer, Sunderland, MA, 1990. xvi, 588 pp., illus. $65; paper, $37.95. PMID- 17746931 TI - Products & materials. PMID- 17746932 TI - A CHRISTMAS GREETING. PMID- 17746933 TI - SUN-SPOTS AND THE EARTH. PMID- 17746934 TI - THE INSECTS OF THE YEAR. PMID- 17746935 TI - WEATHER FORECASTS. PMID- 17746936 TI - TEMPERATURE AND ITS CHANGES IN THE UNITED STATES. PMID- 17746937 TI - EARTHQUAKES IN THE UNITED STATES AND CANADA. PMID- 17746938 TI - THE COMING OF THE ROBIN AND OTHER EARLY BIRDS. PMID- 17746939 TI - TORNADOES, AND HOW TO ESCAPE THEM. PMID- 17746940 TI - BLOOMING-TIMES FOR FLOWERS. PMID- 17746941 TI - IMPORTANT AGRICULTURAL STATISTICS. PMID- 17746943 TI - TIDE TABLE. PMID- 17746942 TI - A FEW PERTINENT HINTS TO FARMERS. PMID- 17746944 TI - SEASONS, 1885. PMID- 17746945 TI - MORNING AND EVENING STARS, 1885. PMID- 17746946 TI - FIXED AND MOVABLE FESTIVALS OF THE CHURCH, 1885. PMID- 17746948 TI - SUN-TIME AND CLOCK-TIME. PMID- 17746947 TI - CHRONOLOGICAL CYCLES, 1885. PMID- 17746949 TI - SYMBOLS. PMID- 17746950 TI - ECLIPSES, 1885. PMID- 17746951 TI - RATES OF DOMESTIC POSTAGE. PMID- 17746952 TI - NEW MAPS OF THE HEAVENS. PMID- 17746953 TI - STANDARD TIME-TABLE. PMID- 17746955 TI - THE SUN AND THE PLANETS, THEIR COMPARATIVE DIMENSIONS. PMID- 17746956 TI - MAP OF THE SOLAR SYSTEM. PMID- 17746954 TI - STANDARD TIME. PMID- 17746957 TI - THE OCCURRENCE OF CARBON DIOXIDE: WITH NOTES ON THE ORIGIN AND RELATIVE IMPORTANCE OF SUBTERRANEAN CARBON DIOXIDE. PMID- 17746958 TI - AN INVITATION TO TEACHERS OF SCIENCE. PMID- 17746959 TI - VIRUSES--LIVING OR NON-LIVING? PMID- 17746960 TI - POSSIBLE LANDSLIP SCARS ON THE BOUQUET RIVER AT WILLSBORO, N. Y. PMID- 17746961 TI - THE FIFTIETH ANNIVERSARY OF THE AMERICAN ASSOCIATION OF ANATOMISTS 1888-1938. PMID- 17746962 TI - HATCHING OF THE EGGS OF THE "FAIRY SHRIMP". PMID- 17746963 TI - VITAMIN A AND ROD-CONE DARK ADAPTATION IN CIRRHOSIS OF THE LIVER. PMID- 17746964 TI - EASTERN SECTION OF THE SEISMOLOGICAL SOCIETY OF AMERICA. PMID- 17746965 TI - THE CHOLINERGIC ACTION OF OESTRIN. PMID- 17746966 TI - INFLUENCE OF BILE ACIDS ON EROSIONS OF THE CHICK GIZZARD LINING. PMID- 17746967 TI - VALUE TO THE INDIVIDUAL. PMID- 17746968 TI - UTILITARIAN VALUES OF ZOOLOGICAL SCIENCE. PMID- 17746969 TI - PROPOSED MAGNETIC AND ALLIED OBSERVATIONS DURING THE TOTAL SOLAR ECLIPSE OF JUNE 8, 1918. PMID- 17746970 TI - PROGRESSIVE DEGLACIATION AND THE AMELIORATION OF CLIMATE. PMID- 17746971 TI - A NEW CALENDAR. PMID- 17746972 TI - TRANSLATIONS MADE ACCESSIBLE. PMID- 17746974 TI - NEZARA VIRIDULA AND KERNEL SPOT OF PECAN. PMID- 17746973 TI - DRAWINGS ON LANTERN SLIDES. PMID- 17746975 TI - SECTION E-GEOLOGY AND GEOGRAPHY. II. PMID- 17746977 TI - ANATOMICAL AND MEDICAL KNOWLEDGE OF ANCIENT EGYPT. PMID- 17746976 TI - PSYCHOPHYSICS. PMID- 17746978 TI - ECONOMIC STATISTICS. PMID- 17746979 TI - CONN'S EVOLUTION OF TO-DAY. PMID- 17746981 TI - A National Science Foundation: 1950 Prospects. PMID- 17746980 TI - SIDGWICK'S HISTORY OF ETHICS. PMID- 17746982 TI - Principles of Emulsion Polymerization. PMID- 17746983 TI - Drinking water: new health problem. PMID- 17746984 TI - Basic research productivity. PMID- 17746985 TI - Diesel engines and air pollution. PMID- 17746986 TI - Medical school tuition. PMID- 17746987 TI - Public opinion and energy use. PMID- 17746988 TI - Detection and examination of anthrosols by phosphate analysis. AB - Land-use analysis of anthrosols has been performed by a new, two-part method. A rapid qualitative field test assists in locating past settlements and determining their areal and temporal extent, even where artifacts are missing. The field-test results are verified and samples are analyzed further by quantitative soil phosphate fractionation. Laboratory fractionation reveals much more than the simple phosphate test used at present. Like the chemical field test, it uses minute soil samples and may be invaluable where disturbance of the landscape is forbidden. Phosphate fractions reflect the details of man-induced changes in the soil and the timing of their appearance. PMID- 17746990 TI - Man-made dogs. AB - The origins of the domestic dog are discussed in relation to the hunting and nurturing behavioral patterns of man and the social canids. While it is accepted that the wolf was the progenitor of the dog the possibility that other species of canid were tamed and interbred with early domestic dogs is not disputed. A description is given of the recently extinct Dusicyon australis and it is suggested that this South American canid may have been tamed and then introduced and domesticated by man in the Falkland Islands during the early Holocene. PMID- 17746991 TI - Schism among psychic-watchers. PMID- 17746989 TI - Plant genetics: increasing crop yield. AB - Cell cultures of crop plants provide new opportunities to recover induced mutations likely to increase crop yield. Approaches include regulating respiration to conserve carbon fixed by photosynthesis, and increasing the nutritive value of seed protein. They depend on devising selecting conditions which only desired mutant cells can survive. Protoplast fusion offers some promise of tapping sources of genetic variation now unavailable because of sterility barriers between species and genera. Difficulties in regenerating cell lines from protoplasts, and plants from cells, still hamper progress but are becoming less severe. Recombinant DNA techniques may allow detection and selection of bacterial cell lines carrying specific DNA sequences. Isolation and amplification of crop plant genes could then lead to ways of transforming plants that will be useful to breeders. PMID- 17746992 TI - Cryptology: scientists puzzle over threat to open research, publication. PMID- 17746994 TI - FTC Sues AMA over Code of Ethics. PMID- 17746993 TI - Public gains access to pesticide safety data. PMID- 17746995 TI - More Fingers in the RANN Pie? PMID- 17746996 TI - OTA Council Opts for Big Names. PMID- 17746997 TI - Einstein Skeptical of ESP After All. PMID- 17746999 TI - Housing choices. PMID- 17746998 TI - Carbon dioxide and climate: carbon budget still unbalanced. PMID- 17747000 TI - Energy and the food system. PMID- 17747001 TI - Decisional problems. PMID- 17747002 TI - Surface phenomena. PMID- 17747003 TI - Early flakes from sozudai, Japan: are they man-made? AB - Some archeologists consider the lowest component of the Sozudai site to be evidence of a human occupation of southern Japan during the early Wurm period. Others deny that the Sozudai objects are artifacts. With separate test procedures, flakes in the Sozudai assemblage were identified and compared to the standard developed by A. S. Barnes. These procedures indicate that flakes in the Sozudai assemblage are of human origin. PMID- 17747004 TI - Thermoluminescent determination of prehistoric heat treatment of chert artifacts. AB - In recent years archeologists have become interested in the extent to which prehistoric peoples heat-treated chert prior to shaping it into tools. Thermoluminescent determination of the radiation dose accumulated by an artifact since it was formed or last heated provides a simple, reliable test for such heat treatment. This test can be applied to single artifacts without the need for raw source material for comparison. Results on 25 artifacts from four sites indicate that, for many chert sources, color and luster are not useful indicators of heat treatment by prehistoric peoples. PMID- 17747005 TI - Arthropod invasion of land during late silurian and devonian times. AB - Fossil floras and faunas of a Lower Devonian black shale from Alken, Germany, include aquatic, amphibious, and terrestrial forms. The presence of these forms suggests conditions in favor of an invasion of the land. Various arthropod adaptations to terrestrial life are present, including the development of a preoral cavity. PMID- 17747006 TI - Temperature exposure measured by the use of thermoluminescence. AB - A method has been developed to measure temperature exposure based on the use of the temperature-dependent property of thermoluminescence fade. This property provides a relatively simple and inexpensive method for measuring both average and accumulated temperature exposure without the need for sophisticated temperature-recording equipment. PMID- 17747007 TI - Hydroxyl radical reactivity with diethylhydroxylamine. AB - Diethylhydroxylamine (DEHA) reacts with gas-phase hydroxyl radicals on every third collision, whereas the corresponding reaction in aqueous solution is considerably slower. The high gas-phase reactivity explains the predicted inhibitory effect of DEHA in atmospheric smog processes. Results from the studies in the aqueous phase are helpful in predicting the mechanism of the reaction of DEHA with hydroxyl radicals. PMID- 17747008 TI - Antiallatotropins: inhibition of corpus allatum development. AB - Treatment of newly eclosed adult milkweed bug (Oncopeltus fasciatus) females with precocene 2 prevents secretion of juvenile hormone by inhibition of postimaginal development of the corpus allatum. Ovarian development which is dependent upon juvenile hormone is prevented or reversed, depending upon the timing of precocene treatment. Juvenile hormone secretion is shown to be related to the development of the corpus allatum. PMID- 17747009 TI - ON THE GENETIC ENERGY OF ORGANISMS. PMID- 17747010 TI - THE MEASUREMENT OF SMALL GASEOUS PRESSURES. PMID- 17747011 TI - SOME THOUGHTS CONCERNING THE TEACHING OF CHEMISTRY. PMID- 17747012 TI - PROFESSOR SCHENCK'S RESEARCHES ON THE PREDETERMINATION OF SEX. PMID- 17747013 TI - CONVERSAZIONE OF THE ROYAL SOCIETY. PMID- 17747014 TI - ZOOLOGICAL SOCIETY OF LONDON. PMID- 17747015 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17747016 TI - NOTES ON INORGANIC CHEMISTRY. PMID- 17747018 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17747017 TI - TIIE COMING MEETING OF THE BRITISH ASSOCIATION IN BRISTOL. PMID- 17747019 TI - LIQUID HYDROGEN. PMID- 17747020 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17747021 TI - DISCUSSION AND CORRESPONDENCE. PMID- 17747022 TI - 'THE NEW PSYCHOLOGY.'. PMID- 17747023 TI - THE DEFINITION OF SPECIES. PMID- 17747024 TI - FOSSIL FULGUR PERVERSUM AT AVALON, N. J. PMID- 17747025 TI - Peer Review at ADAMHA. PMID- 17747026 TI - Human cancer: ridiation and chemicals compete. PMID- 17747027 TI - Energy: a greater risk? PMID- 17747028 TI - "Female evanescence". PMID- 17747030 TI - Heavy crude oil. PMID- 17747029 TI - Erratum. AB - In the Research News article "Tournament competition fuels computer chess" (29 June, p. 1396), the figure was reprodeced incorrectly. Black has a third pawn on the black square immediately in front of the black king. The figure and its legend are reproduced herewith. One limitation offull-width search methods in computer chess is called the horizon effect. A human easily sees that white, although it has one less pawn, can win the game by advancing its leftmost pawn across the board, whereupon it is promoted, by the rules of chess, to a queen. The computer, if it does not search enough moves into the future, will not see this outcome and will be excessively concerned about black's apparent material advantage. [Drawing by Eleanor Warner] [See figure in the PDF file]. PMID- 17747031 TI - Control of federal publications. PMID- 17747032 TI - Management of multispecies fisheries. AB - With the overexploitation of many conventional fish stcocks, and growing interest in harvesting new kinds of food from the sea, there is increasing need for managers of fisheries to take account of interactions among species. In particular, as Antarctic krill-fishing industries grow, there is a need to agree upon sound principles for managing the Southern Ocean ecosystem. Using simple models, we discuss the way multispecies food webs respond to the harvesting of species at differrent trophic levels. These biological and economic insights are applied to a discussion of fisheries in the Southern Otean and the North Sea and to enunciate some for harvesting in multispecies systems. PMID- 17747033 TI - Public attitudes to technological progress. PMID- 17747034 TI - Science in Russia is full of holes. PMID- 17747035 TI - Academy Squabbles over Radwaste Report. PMID- 17747036 TI - Global pollution: is the arctic haze actually industrial smog? PMID- 17747037 TI - Ten years later: whence the moon? PMID- 17747038 TI - The liquid state. PMID- 17747039 TI - Interstellar matter. PMID- 17747040 TI - Commonalities. PMID- 17747041 TI - Bacterial photosynthesis. PMID- 17747042 TI - Detection of singly ionized oxygen around jupiter. AB - Forbidden emission from singly ionized oxygen at wavelengths of 3726 and 3729 angstroms has been detected in the inner Jovian magnetosphere. The emission is present between approximately 4 and approximately 7 to 8 Jovian radii from the planet and appears concentrated in the magnetic equator. The line intensity ratio indicates the same plasma characteristics as those derived from observations of forbidden sulfur emission. PMID- 17747043 TI - Sperm in "parhenogenetic" freshwater gastrotrichs. AB - Freshwater members of the phylum Gastrotricha have been considered obligate parthenogens. In Lepidodermelia squammata, the species for which there is most evidence for parthenogenesis, sperm have been discovered. This finding will necessitate reexamination of the nature of sexuality and life cycles and of the concept of "species" in freshwater gastrotrichs. PMID- 17747044 TI - John Bull's Other Universities. PMID- 17747045 TI - Fellowship of the Royal Society. PMID- 17747047 TI - News of Science. PMID- 17747046 TI - Graduate Students in Britain. PMID- 17747048 TI - Relationship of Hormone Dosage to Physiological Response. PMID- 17747049 TI - Mitochondrial Self-Duplication Observed in vitro. AB - In our paper "Mitochondrial self-duplication observed in vitro" [Science 124, 123 (20 July 1956)], the authors of two of the references were incorrectly given. The authors for reference 5 are E. P. Kennedy and A. L. Lehninger; the authors for reference 6 are J. W. Harman and M. Feigelson. PMID- 17747051 TI - Miscellaneous Publications. PMID- 17747050 TI - Fish Scales in a Sediment Core from Linsley Pond, Connecticut. PMID- 17747054 TI - Equipment News. PMID- 17747053 TI - Meetings and Societies. PMID- 17747055 TI - The Future of the AAAS. PMID- 17747056 TI - Meetings & Conferences. PMID- 17747057 TI - The Duty of Dissent. PMID- 17747058 TI - Paul A. Scherer. PMID- 17747059 TI - Association Business. PMID- 17747060 TI - A Report of the Boston Meeting, December 26-31, 1953. PMID- 17747061 TI - Reports of Sections and Societies, Boston Meeting. PMID- 17747062 TI - Association Finances and Membership. PMID- 17747063 TI - Armed Forces Institute of Pathology. PMID- 17747064 TI - Meetings & Conferences. PMID- 17747066 TI - A New University. PMID- 17747065 TI - The Inflorescences of Maize. AB - 1) The development of the maize plant, from germination to the maturation of the seed, is divided into the vegetative, transitional, reproductive, and seed stages. The ear and tassel differentiate and develop in the reproductive stage. 2) The mature tassel is a terminal, staminate inflorescence consisting of a symmetrical, many-rowed central axis and asymmetrical, two-ranked lateral branches. Paired spikelets, one terminal (pedicellate) and the other lateral (sessile), each containing two functional staminate flowers, are borne on the central axis and the lateral branches. 3) In contrast with the tassel, the ear is a pistillate inflorescence produced on a lateral branch. The ear consists of a symmetrical, many-rowed axis on which are paired spikelets, each containing two flowers. In the mature ear, it is difficult to distinguish the pedicellate from the sessile spikelet. There are two pistillate flowers in each spikelet of the ear, but only the terminal flower is functional, while the lateral flower aborts. 4) The mature ear and tassel appear to be different kinds of inflorescences, but if they are examined at the earliest stages in their development they will be found to be basically alike. The differences in the appearance of the two inflorescences at maturity are the result of differences in the differentiating and development of their parts. 5) Each of the morphological characteristics found in the maize inflorescences, except one, is present in other grasses, but the collection of morphological characteristics found in the ear and tassel is unique. One morphological characteristic not found in other grasses but found in the maize ear is the presence of a terminal, fertile, and aborted, lateral flower in each of the paired spikelets. 6) Axillary shoots are produced in acropetal succession in the axil of each leaf. Some of the axillary shoots that are produced at the beginning of the development of the plant may develop as tillers (suckers). The last-produced axillary shoot (or shoots) that is far enough advanced in its development at the initiation of the tassel develops into the ear (or ears). 7) The amount of seed produced per ear is determined by the number of rows of kernels and the number of kernels per row. The number of rows of kernels is determined at the beginning of the initiation of the ear, but the number of kernels per row may vary with the strain and with changes in the environment. Under comparable condition, seed produced per ear is less in plants without tillers than in plants with tillers. The average seed yield per ear is less in multiple-eared types than single-eared types growing under similar conditions. 8) The three major parts of the maize kernel are endosperm, 82 percent; germ, 11 percent; pericarp, seed coats, and tip cap, 7 percent. The composition of the maize kernel is 83 percent carbohydrate, 10 to 11 precent protein, and 4.3 percent oil. Fifty generations of selection for high- and low-protein strains and high- and low-oil strains produced marked changes in the chemical composition of the maize kernel. Beginning with 4.7 percent oil, after 50 generations of selection, the high-oil strain has 15.36 percent and the low-oil strain has 1.01 percent of oil. The protein content was 10.92 percent at the beginning of the selection and reached 19.45 percent in the high-protein strain and 4.91 percent in the low-protein strain after 50 generations of selection. Recovered inbred lines from backcrosses to the high strains have resulted in good-yielding hybrids that produce more protein or oil per acre than standard hybrids. 9) Several factors contribute to the superiority of maize over other cereals as a seed producer. The maize plant is large and, concomitant with its size, it has a large leaf surface, large stem, large root system, and an extensive vascular system. Branching is restricted to a few lateral, pistillate branches in which vegetative development is suppressed. The lateral ear-producing branch (or branches) is so placed on the plant that there are many leaves above and below it. The ear is large in diameter and has seeds that are many times larger than those of other cereals. All the afore-mentioned characteristics, many of which are not present in other grasses, contribute to making the maize plant a superior seed producer. PMID- 17747067 TI - Miscellaneous Publications. PMID- 17747068 TI - Waxy Constituents of the Saw Palmetto, Serenoa repens (Bartr.) Small. PMID- 17747069 TI - Rapid Separation of Diamond from Other Forms of Carbon. PMID- 17747071 TI - RECLAMATION OF THE ARID WEST. PMID- 17747072 TI - RESOLUTIONS ON THE DEATH OF PROFESSOR CHARLES OTIS WHITMAN. PMID- 17747070 TI - RESEARCH AS A FINANCIAL ASSET. PMID- 17747073 TI - THE ST. LOUIS UNIVERSITY EXPEDITION TO COLORADO. PMID- 17747074 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17747075 TI - THE REFORM OF THE CALENDAR. PMID- 17747076 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17747077 TI - THE GOVERNMENT OF UNIVERSITIES. PMID- 17747078 TI - SOME RECENT ADVANCES IN FLUORESCENCE AND PHOSPHORESCENCE. PMID- 17747080 TI - A STRENGTH AND ENDURANCE TEST. PMID- 17747079 TI - NOTES ON THE PRELIMINARY REPORT OF THE COMMITTEE ON THE TEACHING OF MATHEMATICS TO STUDENTS OF ENGINEERING. PMID- 17747082 TI - THE TORREY BOTANICAL CLUB. PMID- 17747081 TI - THE USE OF ACID SOIL FOR RAISING SEEDLINGS OF THE MAYFLOWER, EPIGAEA REPENS. PMID- 17747083 TI - Letters to the editor. PMID- 17747084 TI - Quick publication schemes. PMID- 17747085 TI - Letters to the editor. PMID- 17747086 TI - Egg fanciers. PMID- 17747087 TI - Open letter to president nixon. PMID- 17747088 TI - Letters to the editor. PMID- 17747089 TI - Shortage of caviar. PMID- 17747090 TI - Physical view of cloud seeding. PMID- 17747092 TI - Man-made plant diseases. PMID- 17747093 TI - Tax-exempt foundations: their effects on national policy. PMID- 17747091 TI - Apollo 13 lunar heat flow experiment. PMID- 17747094 TI - U. Of michigan: black activists win a change in priorities. PMID- 17747095 TI - HEW: What Will Decentralization Mean to Research Evaluation? PMID- 17747097 TI - Arms talks: in-group debate on the technical issues. PMID- 17747098 TI - Missile inpacts as sources of seismic energy on the moon. AB - Seismic signals recorded from impacts of missiles at the White Sands Missile Range are radically different from the signal recorded from the Apollo 12 lunar module impact. This implies that lunar structure to depths of at least 10 to 20 kilometers is quite different from the typical structure of the earth's crust. Results obtained from this study can be used to predict seismic wave amplitudes from future man-made lunar impacts. Seismic energy and crater dimensions from impacts are compared with measurements from chemical explosions. PMID- 17747099 TI - Petroleum lumps on the surface of the sea. AB - Lumps of crude oil residue floating the sea surface have been observed widely. Samples were taken with surface-skimming nets in the Mediter-ranean Sea and eastern North Atlantic Ocean; their displacement volumes were as large as 0.5 milliliter per square meter. An isopod, Idotea metallica, appears to be associated with the lumps, and a barnacle, Lepas pectinata, grows upon them. Lumps were found in stomachs of Scomberesox saurus, a surface-feeding fish importanit in ocean food webs. Films on the lumps, presumably consisting mostly of bacteria, consumed oxygen at the rate of 4 cubic millimeters per hour per square centimeter of lump surface. Chemical analysis suggested that certain lumps had been at large for only a few weeks; data from barnacle size and growth rate suggested that other lumps were at least 2 months old. PMID- 17747100 TI - Secular changes in the lunar elements. AB - Corrections to the adopted values for centennial rates of change of four elements of the lunar orbit, the location of the FK4 equinox, and the obliquity of the ecliptic are presented. They are derived from analyses of lunar occultations distributed over several centuries. Generally, these corrections help to resolve existing discrepancies between theory and observations. PMID- 17747101 TI - Helium isotope effect in solution in water and seawater. AB - The isotope effect in the solution of helium in water from 0 degrees to 40 degrees C has been determined by microgasometric measurements of the solubilities of pure helium-3 and helium4. At 0 degrees C helium-3 is less soluble than helium 4 in both distilled water and sea-water by 1.2 percent. The observed fractionation factor is 0.988+/-0.002 at 0 degrees C and appears to decrease with increasing temperature at the rate of 0.0001 per degree Centigrade, although the existence of this trend is of limited statistical certainty. The measured isotope effect is in agreement with the ratio of helium-3 to helium-4 in surface ocean water reported by Clarke, Beg, and Craig. PMID- 17747102 TI - Xenon Hexafluoride: Structure of a Cubic Phase at -80{degrees}C. AB - The crystal structure of a cubic phase of composition XeF(6) has been determined at -80 degrees C. There are no simple molecules in the complex structure which involves 1008 atoms distributed over 1600 positions per unit cell. Ions of XeF(5)+ and F- are associated in tetrameric and hexameric rings of point group symmetries 4 and 32, respectively. The structure contains right-and left-handed conformations of both tetramers and hexamers. The handedness of the tetramers is dis-ordered but the orientation is ordered. The handedness of the hexamers is ordered but the orientation is disordered. PMID- 17747104 TI - Toxic Factor Produced by a Granulosis Virus in Armyworm Larva: Effect on Apanteles militaris. AB - The internal parasitoid Apanteles militaris is affected by a proteinaceous toxic factor in the hemolymph of granulosis virus-infected armyworm larva. The hemolymph, after centrifugation to remove the virus particles and inoculation into the larval hemocoel, is still toxic to the parasitoids. PMID- 17747103 TI - Differential isotopic fractionation in benthic foraminifera and paleotemperatures reassessed. AB - Different species of benthic Foraminifera taken at the same level in an Atlantic core yielded different oxygen isotopic values. It was therefore impossible to deduce paleotemperature values. In addition, pelagic and benthic species showed the same isotopic variations, an indication that pelagic and benthic species reflect only the variation of oxygen-18 composition of the ocean. PMID- 17747106 TI - Vitreous water: identification and characterization. PMID- 17747105 TI - Alarm Response of Diadema antillarum. AB - Diadema antillarum possesses a sensitive escape response to juices of crushed conspecific sea urchins. Stimulation usually results in urchins moving rapidly downcurrent. Strong species specificity of the response suggests that it is an adaptation to reduce predation. Diadema antillarum also responds with a running response to contact with Cassis tuberosa, a known predator. PMID- 17747107 TI - Separation of plant particles. PMID- 17747108 TI - Courses. PMID- 17747109 TI - SCIENCE NEWS. PMID- 17747110 TI - THE DEVELOPMENT OF SCIENTIFIC RESEARCH IN THE SOUTH. PMID- 17747111 TI - THE EARLY DAYS OF THE AMERICAN PHYSIOLOGICAL SOCIETY. PMID- 17747112 TI - PLEISTOCENE MAN IN MINNESOTA. PMID- 17747113 TI - REPORTS OF THE PRINCETON UNIVERSITY EXPEDITIONS TO PATAGONIA. PMID- 17747114 TI - SOLAR AND RADIO PERIODICITIES. PMID- 17747116 TI - CONFERENCE ON ASTROPHOTOGRAPHIC PROBLEMS. PMID- 17747115 TI - THE LITERATURE OF TAXONOMY. PMID- 17747117 TI - AN APPEAL TO AMERICAN BIOCHEMISTS. PMID- 17747118 TI - BUSINESS PROCEEDINGS OF THE EXECUTIVE COMMITTEE. PMID- 17747119 TI - A SHORT METHOD FOR CALCULATING MOISTURE PERCENTAGES. PMID- 17747120 TI - THE CHEMICAL STUDY OF INSULIN. PMID- 17747121 TI - A BALANCE FOR LIVE ANIMALS. PMID- 17747122 TI - THE ISOLATION OF CRYSTALLINE PROGESTIN. PMID- 17747123 TI - THE NEW ERGOT ALKALOID. PMID- 17747125 TI - A TERMINOLOGY PROPOSED FOR MOTION PICTURE FILMS. PMID- 17747124 TI - SHALL THE DEPARTMENT OF THE INTERIOR BECOME THE DEPARTMENT OF CONSERVATION AND WORKS? PMID- 17747126 TI - A REVIEW OF EVIDENCE RELATING TO THE STATUS OF THE PROBLEM OF ANTIQUITY OF MAN IN FLORIDA. PMID- 17747127 TI - CONSTRUCTION OF A CARTESIAN NOMOGRAM FOR THE LAW OF MASS ACTION. PMID- 17747128 TI - BIOLOGY OF SHELL-MOVEMENTS OF THE OYSTER. PMID- 17747129 TI - A SIMPLE METHOD FOR READING FILM-STRIPS. PMID- 17747130 TI - SEPARATION OF ONE COMPONENT OF POTATO RUGOSE MOSAIC BY PH DIFFERENCE. PMID- 17747131 TI - ON THE SITE OF ACTION OF ACETYLCHOLINE AND ITS SIGNIFICANCE. PMID- 17747132 TI - PIGMENTATION IN BLACK-HAIRED RATS. PMID- 17747133 TI - THE HIGHER SCHOOLS OF NORWAY. PMID- 17747134 TI - ACCLIMATIZATION IN NEW ZEALAND. PMID- 17747135 TI - MENTAL SCIENCE. PMID- 17747136 TI - ETHNOLOGY. PMID- 17747137 TI - HEALTH MATTERS. PMID- 17747138 TI - Over-Pressure in the Schools. PMID- 17747139 TI - Percentage of Ash in Human Bones of Different Ages. PMID- 17747140 TI - Color-Blindness. PMID- 17747142 TI - American Caves. PMID- 17747141 TI - Objects in Teaching. PMID- 17747143 TI - Sections of Fossils. PMID- 17747144 TI - Grindelia glutinosa in Wisconsin. PMID- 17747145 TI - Evidence of a Glacier-like Movement amongst Snow Particles. PMID- 17747146 TI - The State Department's Opportunity in Science. AB - In the editorial "The State Department's opportunity in science" [D. W., Science 123, 205 (10 Feb. 1956)] the word misrepresentation in the last sentence of the third paragraph is a typographical error. The sentence should read: "In sharp contrast with many excellent recommendations of the Hoover Commission, this one seems to us to be completely wrong and probably to arise from a misinterpretation of the attaches' functions." PMID- 17747147 TI - Symposia in Utopia. PMID- 17747148 TI - Modern Structural Chemistry. PMID- 17747149 TI - News of Science. PMID- 17747150 TI - L. H. Snyder, President Elect. PMID- 17747151 TI - AAAS Membership. PMID- 17747153 TI - Reports of Sections and Societies, Atlanta Meeting. PMID- 17747152 TI - Atlanta Meeting in Retrospect. PMID- 17747154 TI - Miscellaneous Publications. PMID- 17747157 TI - Equipment News. PMID- 17747156 TI - Scientific Meetings. PMID- 17747158 TI - UNIFORM TIME. PMID- 17747159 TI - HOW TO OBTAIN THE BRAIN OF THE CAT. PMID- 17747160 TI - ATOMS AND MONADS, THEIR METAPHYSICAL DEVELOPMENT. PMID- 17747162 TI - LETTERS TO THE EDITOR. PMID- 17747161 TI - ASTRONOMY. PMID- 17747163 TI - HOW DOES GRAVITY CAUSE MOTION? PMID- 17747164 TI - THE ADVANCEMENT OF MEDICINE BY RESEARCH. PMID- 17747165 TI - THE DECORATIVE ART OF THE INDIANS OF THE NORTH PACIFIC COAST. PMID- 17747166 TI - RECENT HYDROGRAPHIC EXAMINATIONS IN THE APPALACHIAN AREA. PMID- 17747167 TI - AN ASTRONOMICAL CIPHER CODE. PMID- 17747168 TI - CURRENT NOTES ON PHYSIOGRAPHY. PMID- 17747169 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17747170 TI - ASTRONOMY. PMID- 17747171 TI - THE DAVY-FARADAY RESEARCH LABORATORY. PMID- 17747172 TI - NERVOUS DISEASES AND MODERN LIFE. PMID- 17747173 TI - AN INHERITED BLUNDER. PMID- 17747174 TI - ON A FLICKER PHOTOMETER. PMID- 17747175 TI - THE NEW YORK ZOOLOGICAL PARK. PMID- 17747176 TI - ENGINEERING NOTES. PMID- 17747177 TI - CURRENT NOTES ON PHYSIOGRAPHY. PMID- 17747178 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17747179 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17747180 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17747181 TI - THE THIRD INTERNATIONAL CONGRESS OF APPLIED CHEMISTRY. PMID- 17747183 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17747182 TI - DISCUSSION AND CORRESPONDENCE. PMID- 17747184 TI - ELECTRICAL ANAeSTHESIA. PMID- 17747186 TI - SCIENTIFIC JOURNALS. PMID- 17747185 TI - A PRECISE CRITERION OF SPECIES. PMID- 17747187 TI - SCIENCE NEWS. PMID- 17747189 TI - THE DISCOVERY OF AN ANCIENT MINNESOTA MAKER OF YUMA AND FOLSOM FLINTS. PMID- 17747190 TI - BACTERIA-FREE CULTURE OF PARAMECIUM. PMID- 17747188 TI - ARE THERE PERIODS IN AMERICAN BUSINESS ACTIVITY? PMID- 17747191 TI - OCCURRENCE OF A PHYTOSTEROL IN AFRICAN OIL PALM (ELAEIS GUINEENSIS). PMID- 17747192 TI - A POSSIBLE DIETARY PREDISPOSITION TO STAMMERING. PMID- 17747193 TI - THE SCARRITT EXPEDITIONS OF THE AMERICAN MUSEUM OF NATURAL HISTORY, 1930-34. PMID- 17747195 TI - AN APPARATUS FOR COLORIMETRIC OXIDATION-REDUCTION STUDIES. PMID- 17747194 TI - THE OBSERVATION OF MITOSIS IN THE LIVING CELL IN AMOEBA PROTEUS. PMID- 17747196 TI - DEUTERIUM CONTENT OF NATURAL BUTANE. PMID- 17747197 TI - COPYING MANUSCRIPTS ON MOTION PICTURE FILM. PMID- 17747198 TI - THE RESPONSE OF THE NORMAL GUINEA PIG TO THE ADMINISTRATION OF LIVER EXTRACTS. PMID- 17747199 TI - THE ANAEROBIC CONDITION OF SOILS IN POROUS PORCELAIN CONTAINERS. PMID- 17747200 TI - Translations from the Russian. PMID- 17747201 TI - Neolithic Period in Switzerland and Denmark. PMID- 17747202 TI - Copenhagen Natural Radiocarbon Measurements II. PMID- 17747204 TI - Mutations in Flax Rust Induced by Ultraviolet Radiation. PMID- 17747205 TI - Effect of Free Radicals on Chromosomes of Barley. PMID- 17747203 TI - News of Science. PMID- 17747206 TI - Radiostrontium Fallout from Continuing Nuclear Tests. PMID- 17747207 TI - Miscellaneous Publications. PMID- 17747209 TI - Meetings and Societies. PMID- 17747210 TI - Erratum. AB - In the report "Estrogen and the growth or breast cancer: New evidence suggests indirect action" by S. M. Shafie (8 Aug., p. 701). the following sentence was omitted from the end of the next to last paragraph: "This interpretation is consistent with that of C. Sonnenschein and A. M. Soto [J. Natil. Cancer Inst. 64. 211 (1980)] suggesting that estrogen is not per se a growth promoting agent." PMID- 17747211 TI - Between disciplines. PMID- 17747212 TI - Power wheeling. PMID- 17747213 TI - Environmental regulation. PMID- 17747214 TI - Recurrent intraplate tectonism in the new madrid seismic zone. AB - For the first time, New Madrid seismicity can be linked to specific structural features that have been reactivated through geologic time. Extensive seismic reflection profiling reveals major faults coincident with the main earthquake trends in the area and with structural deformation apparently caused by repeated episodes of igneous activity. PMID- 17747216 TI - Recombinant DNA. PMID- 17747215 TI - The archeology of alaska and the peopling of america. AB - The proposed existence of a biotically productive tundra-steppe on the exposed Bering Land Bridge of the late Pleistocene aids conceptualization of the migrations of early Asian hunters. But clear knowledge of the human occupants of north-westernmost America before 11,000 years ago is elusive. Evidence indicates that at that time the Alaskan peoples had a culture generally based on microliths that, while obviously derived from Asia, were not sufficiently similar to the tools of the earliest widely distributed hunters of more southerly North America to support any direct and close relation between the two cultures. PMID- 17747217 TI - Cryptography: a new clash between academic freedom and national security. PMID- 17747218 TI - Navy lab concludes the vela saw a bomb. PMID- 17747219 TI - Cancer Patients: Joints or THC? PMID- 17747220 TI - Aquarian candidate quizzed by laureates. PMID- 17747222 TI - France, iraq, and the bomb. PMID- 17747221 TI - French doctors claim shah had wrong treatment. PMID- 17747223 TI - Continuing Confusion over Love Canal. PMID- 17747225 TI - Designing by the rules is not always enough. PMID- 17747224 TI - How much is too much when the Earth quakes? PMID- 17747226 TI - Wars and the environment. PMID- 17747227 TI - Complex carbohydrates. PMID- 17747228 TI - Water in the atmosphere. PMID- 17747229 TI - Human nutrition. PMID- 17747230 TI - Aeromagnetic and radio echo ice-sounding measurements show much greater area of the dufek intrusion, antarctica. AB - A combined aeromagnetic and radio echo ice-sounding survey made in 1978 in Antarctica over the Dufek layered mafic intrusion suggests a minimum area of the intrusion of about 50,000 square kilometers, making it comparable in size with the Bushveld Complex of Africa. Comparisons of the magnetic and subglacial topographic profiles illustrate the usefulness of this combination of methods in studying bedrock geology beneath ice-covered areas. Magnetic anomalies range in peak-to-through amplitude from about 50 nanoteslas over the lowermost exposed portion of the section in the Dufek Massif to about 3600 nanoteslas over the uppermost part of the section in the Forrestal Range. Theoretical magnetic anomalies, computed from a model based on the subice topography fitted to the highest amplitude observed magnetic anomalies, required normal and reversed magnetizations ranging from 10(-3) to 10(-2) electromagnetic units per cubic centimeter. This result is interpreted as indicating that the Dufek intrusion cooled through the Curie isotherm during one or more reversals of the earth's magnetic field. PMID- 17747231 TI - Cytoplasmic Reversion of cms-S in Maize: Association with a Transpositional Event. AB - Spontaneous reversion to fertility in S male-sterile cytoplasm of maize is correlated with the disappearance of the mitochondrial plasmid-like DNA's, S-1 and S-2, and changes in the mitochondrial chromosomal DNA. Hybridization data indicate that one of the plasmid-like DNA's, S-2, is prominently involved in the mitochondrial DNA rearrangements. PMID- 17747232 TI - Juvocimenes: potent juvenile hormone mimics from sweet basil. AB - Two compounds with highly potent juvenile hormone activity were isolated and identified from the oil of sweet basil, Ocimum basilicum L., Labiatae. PMID- 17747233 TI - Influence of Siphonophore Behavior upon Their Natural Diets: Evidence for Aggressive Mimicry. AB - Collection by divers permitted determination of the natural diets of siphonophore species within II genera. Siphonophores that swim rapidly to spread their tentacles capture small prey, whereas those that swim very weakly capture much larger prey. Nematocyst batteries of two species of weak swimmers closely resemble copepods and fish larvae. Morphology, behavior, and diet suggest that these two species attract large prey by mimicking other zooplankton. PMID- 17747234 TI - Oil and gas in offshore tracts: inexactness of resource estimates prior to drilling. PMID- 17747236 TI - THE DOCTOR'S DREAM. PMID- 17747235 TI - Oil and gas in offshore tracts: inexactness of resource estimates prior to drilling. PMID- 17747237 TI - THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE SCIENCE, EDUCATION AND DEMOCRACY. PMID- 17747239 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17747238 TI - THE PROFESSORSHIP OF PHILOSOPHY AND PSYCHOLOGY AT LAFAYETTE COLLEGE. PMID- 17747240 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17747241 TI - TUBERCULOSIS FOLLOWING TYPHOID FEVER. PMID- 17747242 TI - THE ORIGIN OF CLIMATIC CHANGES. PMID- 17747244 TI - THE AMERICAN PHYSIOLOGICAL SOCIETY. PMID- 17747243 TI - THE EFFECT OF COLD UPON THE LARVAe OF TRICHINELLA SPIRALIS. PMID- 17747245 TI - THE AMERICAN PHYTOPATHOLOGICAL SOCIETY. PMID- 17747246 TI - THE PALEONTOLOGICAL SOCIETY. PMID- 17747247 TI - SCIENCE NEWS. PMID- 17747248 TI - INTERNATIONAL COOPERATION IN GEOGRAPHICAL WORK. PMID- 17747249 TI - THE FUTURE OF TAXONOMY. PMID- 17747250 TI - BANANA STOWAWAYS AGAIN. PMID- 17747251 TI - CONGLOMERITE, A NEW ROCK TERM. PMID- 17747252 TI - PRESSURE POTENTIAL IN A FLUID. PMID- 17747253 TI - WHEN BELIEVING IS SEEING--AN OPTICAL ILLUSION. PMID- 17747254 TI - THE WESTERN COOPERATIVE OIL SPRAY PROJECT (1929). PMID- 17747255 TI - SEDIMENTATION TUBE FOR MECHANICAL ANALYSES. PMID- 17747256 TI - THE CHEMICAL CONTROL OF SPLENIC CONTRACTION. PMID- 17747257 TI - STOCK CULTURES OF AMEBA. PMID- 17747258 TI - THE CHEMICAL NATURE OF CYPRIDINA LUCIFERIN. PMID- 17747259 TI - Two Weeks B.C. PMID- 17747260 TI - Archeology and Geology in Ancient Egypt. PMID- 17747261 TI - Fashion in Cell Biology. PMID- 17747262 TI - AAAS New York Meeting. PMID- 17747263 TI - Science Advisory Committee and National Goals Reports Emphasize Growing Roles of Government. PMID- 17747264 TI - U.N. Asked To Aid Birth Control; Sweden Appeals; Connecticut Court Upholds Curb. PMID- 17747265 TI - Calorimetry Group Adopts Revised Resolution on Data Publication. PMID- 17747266 TI - Effect of Synthetic Polylysine on Fungi. AB - The synthetic, basic poly-alpha-amino acid, polylysine, had antifungal activity against plant pathogens (three strains of fusaria, three isolates of verticillia, and Ceratocystis fimbriata) and against the human pathogens (Trichophyton mentagrophytes, T. rubrum, and Candida albicans) in vitro. It inhibited penetration of Ceratocystis fimbriata on sweet potato slices. Polylysine inhibited the infection of tomato cuttings by Flsarium oxysporum f. lycopersici, but it was also toxic to the plants. PMID- 17747267 TI - Isolation of trans-Aconitic Acid from the Moss Mnium affine. AB - The water-soluble substance occurring in high concentration (up to 6 percent of the dry weight) in Mnium affine Bland. and forming the main fraction of the plant acids there, has been identified as trans-aconitic acid by nine different criteria. Evidence is presented in favor of the concept that the trans form in this case is the natural isomer and not an artifact derived from cis-aconitic acid. Information is given on the distribution of aconitic acid in other mosses and in liverworts. PMID- 17747268 TI - Further Competitive Exclusion. PMID- 17747269 TI - Letters to the Editor. PMID- 17747270 TI - Social Responsibility. PMID- 17747271 TI - American Men of Science. PMID- 17747272 TI - Open Literature. PMID- 17747273 TI - Letters to the Editor. PMID- 17747274 TI - Stilbestrol. PMID- 17747275 TI - Life Shortening and Production of Tumors by Strontium-90. PMID- 17747276 TI - Perception of Apparent Motion. PMID- 17747277 TI - Letters to the Editor. PMID- 17747278 TI - Reprint Exchange Center. PMID- 17747279 TI - Developmental Selection of Mutations. PMID- 17747280 TI - Village Solidarity. PMID- 17747281 TI - Letters to the Editor. PMID- 17747282 TI - Grants and Scientific Freedom. PMID- 17747283 TI - Letters to the Editor. PMID- 17747285 TI - Physicomathematical Aspects of Biology. PMID- 17747284 TI - McCollum-Pratt Symposium. PMID- 17747287 TI - The 112th Annual Meeting of the British Association for the Advancement of Science. PMID- 17747286 TI - Forthcoming Events. PMID- 17747288 TI - The New York Meeting, AAAS December 26-31, 1949. PMID- 17747289 TI - THE ADMINISTRATION OF GOVERNMENT SCIENTIFIC WORK. PMID- 17747290 TI - A DETERMINATION OF THE NATURE AND VELOCITY OF GRAVITATION. PMID- 17747291 TI - ADDRESS OF THE PRESIDENT OF THE SECTION OF GEOLOGY OF THE BRITISH ASSOCIATION. PMID- 17747293 TI - ON THE SUPERINTENDENCY AND ORGANIZATION OF THE COAST SURVEY. PMID- 17747292 TI - THE GEOLOGICAL AND PALEONTOLOGICAL COLLECTIONS IN THE AMERICAN MUSEUM OF NATURAL HISTORY. PMID- 17747294 TI - NOTES ON INORGANIC CHEMISTRY. PMID- 17747296 TI - THE ANNUAL CONGRESS OF THE GERMAN ANTHROPOLOGICAL SOCIETY. PMID- 17747295 TI - RECENT ZOO-PALEONTOLOGY. PMID- 17747297 TI - SECTION OF HORTICULTURE AND BOTANY OF THE ASSOCIATION OF AGRICULTURAL COLLEGES AND EXPERIMENT STATIONS. PMID- 17747298 TI - Letter to the editor. PMID- 17747299 TI - Letter to the editor. PMID- 17747300 TI - Ph.D.'s Coming and Going. PMID- 17747301 TI - Averting nuclear blackmail. PMID- 17747302 TI - Solar eclipse information. PMID- 17747303 TI - Letter to the editor. PMID- 17747304 TI - Conservation and the minerals industry. PMID- 17747305 TI - Holography. AB - Research on holography has now grown to such dimensions that we have not been able to mention each of the numerous authors who have made significant contributions to it. Investigators from Bell Telephone Laboratories, the RCA, Xerox, and Westinghouse laboratories, Conductron Corporation, GC-Optronics, IBM, TRW Systems, the University of Michigan, and Stanford University have made particularly significant early contributions in the United States. Especially notable were the efforts of R. J. Collier, L. Lin, K. S. Pennington, D. Ansley, L. Siebert, R. M. Grant, A. Lohmann, R. F. Wuerker, K. Stetson, R. Powell, J. Goodman, and their co-workers, in addition to those already mentioned, among many others. Early work in many parts of the world also includes that in France by S. Lowenthal, G. Nomarski, and J. Viepsilonnot; in Germany by H. Nassenstein; in Great Britain by J. M. Burch; in Japan by J. Tsujiuchi and T. Tsuruta; and in the Soviet Union by Yu. Y. N. Denisyuk, I. Nalimov, and L. M. Soroko. For a fuller account of these developments, see (42) and other references. PMID- 17747307 TI - Reflections on the decline of science in america and on some of its causes. PMID- 17747306 TI - A gorilla-sized ape from the miocene of India. AB - A large ape existed in India at the close of the Miocene or the beginning of the Pliocene epochs; this ape shows a complex of anatomical structures at the opposite pole from its contemporary, Ramapithecus. Although found in the same beds, the two seldom occur at the same exact sites and levels. Considering the thickness of these beds, recovery close to Haritalyangar does not, of itself, prove sympatry of these two different kinds of Hominoidea. However, both are definitely present at one recently located site representing, most probably, a death assemblage. Observations by the authors on scores of chimpanzees suggest that, at least in this ape, wear gradients on molar crowns exist, but that the wear differential between adjacent molars is almost never raised to the degree seen in most Ramapithecus. Dryopithecus itdicus and D. fontani (from southern France), in contrast, show almost no wear gradient at all; that is, whether an individual is dentally young or old, wear on all three molars and the two premolars has proceeded to about the same degree. It is of considerable importance in understanding hominid phylogeny to be able to stress that an ape known to be contemporary with Ramapithecus shows far less differential wear than does the hominid. This, in turn, strongly suggests that the molar eruption sequence of D. indicus was rapid, while that of the hominid was delayed. The implication is that, as far back as the late Miocene, the hominid maturation period was lengthened, relative to that of apes. A further fact which emerges is that the rate of interstitial wear was faster in the Haritalyangar ape than in the hominid contemporary with it. This, together with its large size, flatness of unworn tooth crowns, and other associated characters, suggests that D. indicus is in, or close to, the ancestry of Gigantopithecus. From this emerges yet another object lesson, emphasizing the caution one has to observe in the manner and method by which ancient and modern apes are compared and contrasted. None of the species of Hominoidea dealt with here, whether pongid (D. indicus and Pan troglodytes) or hominid (R. punjabicus), accumulates either interstitial or crown wear at the same rate or in the same manner. PMID- 17747308 TI - Britain: Successor to "Mintech" Loses Jurisdiction over Research. PMID- 17747309 TI - Princeton-pennsylvania accelerator: end of an era in particle physics. PMID- 17747310 TI - Behavioral sensitivity to microwave irradiation. AB - In "Behavioral sensitivity to microwave irradiation" by N. W. King et al. (23 Apr., p. 398), lines 1 to 8, coltumn 2, page 399, should read " basis of the level of focusing current used to control and monitor the output power of the magnetron (25). A shift from zero to a present level of available power in the exposure cavity was accomplished by applying 5 kv of 60-hz a-c voltage to the anode of the magnetron." PMID- 17747311 TI - The southern corn leaf blight epidemic. AB - In "The sotuthern corn leaf blight epidemic" by L. A. Tatum (19 Mar., p. 1113), the first sentence of the third paragraph under the sidehead "History of southern corn leaf blight" on page 1114 should read "The loss in 1969 rather than "1968." PMID- 17747312 TI - Plate Tectonics: The Geophysics of the Earth's Surface. PMID- 17747313 TI - Alpha-recoil thorium-234: dissolution into water and the uranium-234/uranium-238 disequilibrium in nature. AB - The rate of ejection of alpha-recoil thorium-234 into solution from the surface of zircon sand gives an alpha-recoil range of 550 angstroms. The alpha-recoil thorium-234 atoms ejected into the groundwater may supply excess uranium-234. In pelagic sediments, ejected alpha-recoil thorium-234 may contribute to the supply of mobile uranium-234 in the sedimentary column. PMID- 17747314 TI - Motion-induced inhibition of elongation and induction of dormancy in liquidambar. AB - Moderate shaking of Liquidambar trunks for 30 seconds daily reduced height growth to only 20 to 30 percent of that of trees not shaken. Six of eight trees shaken set terminal buds within 3 weeks. The trees which were not shaken formed no terminal buds. An endogenous mechanism for regulating tree growth in windy situations is implicated. PMID- 17747315 TI - Southern corn leaf blight: susceptible and resistant mitochondria. AB - Mitochondria isolated from etiolated shoots of blight-susceptible and blight resistant corn plants were subjected, in various respiratory states, to the pathotoxin released by Helminthosporium maydis (race T). The addition of the pathotoxin to susceptible mitochondria caused respiratory rate and oxidative phosphorylation changes. The addition of pathotoxin to susceptible mitochondria suspended in a potassium chloride reaction medium induced an immediate and irreversible swelling regardless of the respiratory state of the mitochondria. This membrane swelling correlates with the observed respiratory and coupling effects of the pathotoxin. In all instances, mitochondria isolated from blightresistant corn failed to exhibit any of the above responses to the pathotoxin. PMID- 17747317 TI - CHARLES FREDERICK MARVIN. PMID- 17747316 TI - THE ORIGIN OF LANGUAGE. PMID- 17747318 TI - THE NATIONAL FOUNDATION FOR INFANTILE PARALYSIS. PMID- 17747319 TI - THE BIRTHDAY HONORS OF THE KING OF ENGLAND. PMID- 17747320 TI - THE TERCENTENARY COMMEMORATION OF THE INVENTION OF THE BAROMETER. PMID- 17747322 TI - THE PITTSBURGH MEETING OF THE AMERICAN CHEMICAL SOCIETY. PMID- 17747321 TI - THE INTERNATIONAL COMMISSION ON ZOOLOGICAL NOMENCLATURE. PMID- 17747323 TI - THE CONCEPT OF CELLS HELD BY HOOKE AND GREW. PMID- 17747324 TI - THE HYDROLYSIS OF d-PEPTIDES. PMID- 17747325 TI - THE INSTITUTE OF TROPICAL AGRICULTURE AT TURRIALBA. PMID- 17747326 TI - ABOLISHMENT OF ALIMENTARY LIPEMIA FOLLOWING INJECTION OF HEPARIN. PMID- 17747327 TI - PRODUCTION AND TREATMENT OF GRANULOCYTOPENIA AND ANEMIA IN RATS FED SULFONAMIDES IN PURIFIED DIETS. AB - (1) A severe granulocytopenia or anemia, or both, have been produced in rats fed sulfathiazole, sulfadiazine or sulfanilamide at a 1 per cent. level in purified diets. (2) Treatment with certain liver fractions orally has succeeded in correcting the granulocytopenia in four days and the anemia in about 10 days in spite of continued ingestion by these animals of the sulfonamide-containing diet. PMID- 17747328 TI - THE DETERMINATION OF CELL VOLUME AND HEMOGLOBIN ON THE SAME DROP OF BLOOD. PMID- 17747329 TI - GROWTH OF ORCHID SEEDS AFTER DEHYDRATION FROM THE FROZEN STATE. PMID- 17747330 TI - COMMENT AND CRITICISM. PMID- 17747332 TI - THE HEALTH OF NEW YORK DURING DECEMBER. PMID- 17747331 TI - THE SUBMERGED TREES OF THE COLUMBIA RIVER. PMID- 17747333 TI - PARIS LETTER. PMID- 17747334 TI - National prosperity. PMID- 17747335 TI - Professor Newberry on earthquakes. PMID- 17747337 TI - Spiders and the electric light. PMID- 17747336 TI - A pineal eye in the mesozoic Mammalia. PMID- 17747338 TI - Loco-weed. PMID- 17747339 TI - A card to American geologists. PMID- 17747340 TI - Letters. PMID- 17747341 TI - Letters. PMID- 17747342 TI - Social science: identifying major advances. PMID- 17747343 TI - Registry of women scientists. PMID- 17747344 TI - Opportunities in plant science. PMID- 17747345 TI - Leg 4 of the deep sea drilling project. PMID- 17747346 TI - Reactor Emissions: AEC Guidelines Move Toward Critics' Position. PMID- 17747347 TI - ROTC: Education Groups' Reforms Stress Flexibility, Fuller Funding. PMID- 17747348 TI - Curriculum vitae: a man of his times. PMID- 17747349 TI - Nuclear tests: big amchitka shot target of mounting opposition. PMID- 17747350 TI - Developmental behaviors: delayed appearance in monkeys asphyxiated at birth. AB - In "Developmental behaviors: delayed appearance in monkeys asphyxiated at birth" by J. A. Sechzer et al. (19 Mar., p. 1173), the last two lines of column 1 and the first five lines of column 2, page 1175, should read "Deficits in learning and memory (10, 11) when compared with the establishment of these developmental behaviors (although significantly delayed) suggest that brain damage by neonatal asphyxia can result in a degree of dissociation..." PMID- 17747351 TI - Nimbus weather satellites: remote sounding of the atmosphere. PMID- 17747352 TI - Soil: a natural sink for carbon monoxide. AB - A potting soil mixture depleted carbon monoxide in a test atmosphere from a concentration of 120 parts per million to near zero within 3 hours. Maximum activity occurred at 30 degrees C. Steam sterilization of the soil, the addition of antibiotics or 10 percent (by weight) saline solution, and anaerobic conditions all prevented carbon monoxide uptake. Sterilized soil inoculated with nonsterile soil acquired activity with time. Samples of various natural soils differed in their ability to remove carbon monoxide from the air. Acidic soils with a high content of organic matter were generally the most active. The soil's ability to remove carbon monoxide from the atmosphere is ascribed to the activity of soil micro-organisms. PMID- 17747353 TI - Net kinetic energy in littoral transport. AB - Studies of coastal erosion and coastal management can be put on a firm physical basis only after methods have been developed for closely estimating the energy expended in actual unidirectional net littoral transport of sediment. Such measures have now been obtained for six coastal drift cells. The results, for a 68-year period, vary from a minimum of 0.6 x 10(4) ergs (very low energy) to a maximum of 340 x 10(4) ergs (moderately high energy) per cell. PMID- 17747354 TI - THE INTELLECTUAL CONDITIONS FOR EMBRYOLOGICAL SCIENCE. PMID- 17747355 TI - THE NATURE OF NERVE STIMULATION AND OF CHANGES IN IRRITABILITY. PMID- 17747356 TI - NODULES AND MOLECULES OF RED BLOOD-CORPUSCLES. PMID- 17747357 TI - AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE: ANTHROPOLOGY. PMID- 17747359 TI - FELIS OREGONENIS RAF. AGAIN! PMID- 17747358 TI - A VERY SENSITIVE THERMOSTAT. PMID- 17747361 TI - SCIENTIFIC NOMENCLATURE. PMID- 17747360 TI - BOTANICAL NOTES. PMID- 17747362 TI - NOTES ON INORGANIC CHEMISTRY. PMID- 17747363 TI - GRAVITY ON THE OCEAN. PMID- 17747364 TI - RECENT ZOOPALEONTOLOGY. PMID- 17747365 TI - BRYAN DONKIN. PMID- 17747366 TI - Cancer prevention: setting priorities. PMID- 17747367 TI - The Cover's Message. PMID- 17747368 TI - Bypassing peer review for scientific facilities. PMID- 17747369 TI - Global deforestation: contribution to atmospheric carbon dioxide. AB - A study of effects of terrestrial biota on the amount of carbon dioxide in the atmosphere suggests that the global net release of carbon due to forest clearing between 1860 and 1980 was between 135 x 10(15) and 228 x 10(15) grams. Between 1.8 x 10(15) and 4.7 x 10(15) grams of carbon were released in 1980, of which nearly 80 percent was due to deforestation, principally in the tropics. The annual release of carbon from the biota and soils exceeded the release from fossil fuels until about 1960. Because the biotic release has been and remains much larger than is commonly assumed, the airborne fraction, usually considered to be about 50 percent of the release from fossil fuels, was probably between 22 and 43 percent of the total carbon released in 1980. The increase in carbon dioxide in the atmosphere is thought by some to be increasing the storage of carbon in the earth's remaining forests sufficiently to offset the release from deforestation. The interpretation of the evidence presented here suggests no such effect; deforestation appears to be the dominant biotic effect on atmospheric carbon dioxide. If deforestation increases in proportion to population, the biotic release of carbon will reach 9 x 10(15) grams per year before forests are exhausted early in the next century. The possibilities for limiting the accumulation of carbon dioxide in the atmosphere through reduction in use of fossil fuels and through management of forests may be greater than is commonly assumed. PMID- 17747370 TI - After Spacelab, Europe Wants a Better Deal: It paid a high price to build Spacelab but is expected to seek a major role in NASA's proposed space station. PMID- 17747371 TI - NSF Seeks Expanded Role in Engineering: National Science Board policy statement sets direction for another effort to achieve so-far elusive objectives. PMID- 17747372 TI - Sag in the market for scientists, engineers. PMID- 17747374 TI - How to transplant biomedical research. PMID- 17747373 TI - Business to boost R & d. PMID- 17747375 TI - WIPP Goes Ahead, Amid Controversy: New Mexico's governor worries less about the nuclear waste project now planned than about the one he suspects DOE may have up its sleeve. PMID- 17747376 TI - The Carbon Cycle and Climate Warming: Learning how carbon cycles through the environment, with and without human intervention, is crucial to predicting the greenhouse effect. PMID- 17747377 TI - Origin of Species in Stressed Environments: Data from marine and terrestrial communities unexpectedly reveal the preferential origin of evolutionary novelties in species-poor environments. PMID- 17747378 TI - The greenian view of botany: landmarks of botanical history. PMID- 17747379 TI - Toxicology: cellular systems for toxicity testing. PMID- 17747380 TI - An african ungulate: a territorial antelope. PMID- 17747381 TI - Ion channels: membrane potential-dependent ion channels in cell membrane. PMID- 17747382 TI - Cosmology: the big bang and element creation. PMID- 17747383 TI - Relativity: the mathematical theory of black holes. PMID- 17747384 TI - Iridium enrichment in airborne particles from kilauea volcano: january 1983. AB - Airborne particulate matter from the January 1983 eruption of Kilauea volcano was inadvertently collected on air filters at Mauna Loa Observatory at a sampling station used to observe particles in global circulation. Analyses of affected samples revealed unusually large concentrations of selenium, arsenic, indium, gold, and sulfur, as expected for volcanic emissions. Strikingly large concentrations of iridium were also observed, the ratio of iridium to aluminum being 17,000 times its value in Hawaiian basalt. Since iridium enrichments have not previously been observed in volcanic emissions, the results for Kilauea suggest that it is part of an unusual volcanic system which may be fed by magma from the mantle. The iridium enrichment appears to be linked with the high fluorine content of the volcanic gases, which suggests that the iridium is released as a volatile IrF(6). PMID- 17747385 TI - Equatorial undercurrent disappears during 1982-1983 el nino. AB - The equatorial undercurrent at 159 degrees W decayed during August 1982, partially reversed during September, and rapidly reappeared in January 1983. The virtual disappearance is consistent with the basin-wide adjustment of sea surface slope to the strong westerly winds in the western and central Pacific that caused the 1982-1983 El Nino event. PMID- 17747387 TI - TO WHAT EXTENT SHOULD THE UNIVERSITY INVESTIGATOR BE FREED FROM TEACHING. PMID- 17747386 TI - Onshore-offshore patterns in the evolution of phanerozoic shelf communities. AB - Cluster analysis of Cambrian-Ordovician marine benthic communities and community trophic analysis of Late Cretaceous shelf faunas indicate that major ecological innovations appeared in nearshore environments and then expanded outward across the shelf at the expense of older community types. This onshoreinnovation, offshore-archaic evolutionary pattern is surprising in light of the generally, higher species turnover rates of offshore clades. This pattern probably results from differential extinction rates of onshore as compared to offshore clades, or from differential origination rates of new ecological associations or evolutionary novelties in nearshore environments. PMID- 17747388 TI - The Dynamics of Living Matter. PMID- 17747389 TI - APPEAL FOR AN AERO-PHYSICAL OBSERVATORY IN JAPAN. PMID- 17747390 TI - AN UNUSUAL METEOR. PMID- 17747391 TI - ON THE OCCURRENCE OF DESMOSTYLUS, MARSH. PMID- 17747392 TI - PROFESSOR HENRY A. WARD. PMID- 17747393 TI - FRITZ SCHAUDINN. PMID- 17747394 TI - THE ROYAL BOTANIC SOCIETY OF LONDON. PMID- 17747395 TI - THE INTERNATIONAL INSTITUTE OF SOCIOLOGY. PMID- 17747396 TI - RESULTS OF THE GERMAN CENSUS. PMID- 17747398 TI - Meetings & Conferences. PMID- 17747397 TI - Publishing Scientific Books. PMID- 17747399 TI - Our Splintered Learning and the Status of Scientists. PMID- 17747400 TI - The Use of Material. PMID- 17747401 TI - Papers of Wilbur and Orville Wright. PMID- 17747402 TI - The Care and Training of Authors. PMID- 17747403 TI - Security and the Editor. PMID- 17747404 TI - Is There Accepted Scientific Jargon? PMID- 17747405 TI - Use of the Technical Report in Military Planning. PMID- 17747406 TI - Clarity in Geological Writing. PMID- 17747408 TI - Technical Manuals: Their Increasing Importance to Industry and Defense. PMID- 17747407 TI - A System for Testing and Increasing the Intelligibility of Technical Reports. PMID- 17747410 TI - Ten Commandments for Technical Writers. PMID- 17747409 TI - That and Which Again. PMID- 17747411 TI - Note on a New Literary Phenomenon. PMID- 17747412 TI - Do Ye unto Others. PMID- 17747413 TI - Achieving Style in Writing. PMID- 17747414 TI - This week in science. PMID- 17747415 TI - "Wise men" on superconductors. PMID- 17747416 TI - Dear President-elect . . : Slowing an Irreversible Experiment. PMID- 17747417 TI - Dear President-elect . . : A Place at the Head Table. PMID- 17747418 TI - FAA Fights Back on Plastic Explosives: The Lockerbie disaster highlights a fast growing and insidious threat, but technical safeguards may be possible nonetheless. PMID- 17747419 TI - Pruning the Thickets of Cosmic Speculation: Cosmology currently suffers from too much theory and not enough data; the new Center for Particle Astrophysics could help. PMID- 17747420 TI - Input management of production systems. AB - Nonpoint sources of pollution, which are largely responsible for stressing regional and global life-supporting atmosphere, soil, and water, can only be reduced (and ultimately controlled) by input management that involves increasing the efficiency of production systems and reducing the inputs of environmentally damaging materials. Input management requires a major change, an about-face, in the approach to management of agriculture, power plants, and industries because the focus is on waste reduction and recycling rather than on waste disposal. For large-scale ecosystem-level situations a top-down hierarchical approach is suggested and illustrated by recent research in agroecology and landscape ecology. PMID- 17747421 TI - Ergodic theory, randomness, and "chaos". AB - Ergodic theory is the theory of the long-term statistical behavior of dynamical systems. The baker's transformation is an object of ergodic theory that provides a paradigm for the possibility of deterministic chaos. It can now be shown that this connection is more than an analogy and that at some level of abstraction a large number of systems governed by Newton's laws are the same as the baker's transformation. Going to this level of abstraction helps to organize the possible kinds of random behavior. The theory also gives new concrete results. For example, one can show that the same process could be produced by a mechanism governed by Newton's laws or by a mechanism governed by coin tossing. It also gives a statistical analog of structural stability. PMID- 17747422 TI - Active polar region on the nucleus of comet halley. AB - The images of the nucleus of comet Halley returned by the Giotto spacecraft reveal a number of active regions on the surface, one of which is near the expected location of the rotation pole. This feature is larger and brighter than other source regions, suggesting that the mechanism that drives this source is also different. At this active region near the rotation pole, the sun was circumpolar for a significant portion of the solar encounter. Continuous insolation heated the nucleus to greater depths than in other areas, producing the broad, active polar region. PMID- 17747423 TI - A relation to describe rate-dependent material failure. AB - The simple relation OmegaOmega-alpha = 0, where Omega is a measurable quantity such as strain and A and alpha are empirical constants, describes the behavior of materials in terminal stages of failure under conditions of approximately constant stress and temperature. Applicable to metals and alloys, ice, concrete, polymers, rock, and soil, the relation may be extended to conditions of variable and multiaxial stress and may be used to predict time to failure. PMID- 17747424 TI - Involvement of juvenile hormone in the regulation of pheromone release activities in a moth. AB - Juvenile hormone has been implicated in the mediation of several reproduction related events in adult insects, but had previously been found to play no role in the regulation of sex pheromone production and release behavior ("calling") in moths. In females of the true armyworm moth, Pseudaletia unipuncta, juvenile hormone is shown to be essential to the initiation of both calling behavior and pheromone production. Females without corpora allata, the source of juvenile hormone, do not call and do not produce pheromone, but injection of juvenile hormone into allatectomized females restored these activities. The armyworm's control system has likely evolved in response to the adults' migratory behavior which may necessitate that mating be restricted to the period following migration. PMID- 17747425 TI - Response: habitat compartmentation and envitonmental correlates of food chain length. PMID- 17747426 TI - Human evolution: new questions: the evolution of human hunting. PMID- 17747427 TI - Rationality and risk: classical probability in the enlightenment. PMID- 17747428 TI - Lamarck in context: the age of lamarck. PMID- 17747429 TI - The sociobiology of plants: plant reproductive ecology. PMID- 17747430 TI - Products & materials. PMID- 17747431 TI - Letters to the Editor. PMID- 17747433 TI - Letters to the Editor. PMID- 17747432 TI - Scientists and Eugenics. PMID- 17747434 TI - "Disjointed Incrementalism". PMID- 17747435 TI - Letters to the Editor. PMID- 17747436 TI - Neologismification. PMID- 17747437 TI - Degrees and Titles. PMID- 17747439 TI - Occurrence of Cilia. PMID- 17747438 TI - Letters to the Editor. PMID- 17747440 TI - Working Hypotheses in Psychotherapy. PMID- 17747441 TI - Mariner IV Mission. PMID- 17747442 TI - Quantum Theory an Elementary Particle. PMID- 17747443 TI - Spider-Web Building. PMID- 17747444 TI - Nuclear Physics: A Status Report. PMID- 17747445 TI - Advice to a New Academy. PMID- 17747446 TI - Science and Government: New Currents Flowing. PMID- 17747448 TI - Education: U.S. Institutions Prepare African Students for Development Tasks at Home. PMID- 17747447 TI - Social Sciences: Cancellation of Camelot after Row in Chile Brings Research under Scrutiny. PMID- 17747449 TI - Is French Scientific Policy Chauvinist? PMID- 17747450 TI - Mariner IV Measurements near Mars: Initial Results. PMID- 17747451 TI - Absence of Martian Radiation Belts and Implications Thereof. AB - A system of sensitive particle detectors on Mariner IV showed the presence of electrons of energy (E(e)) less than 40 kiloelectron volts out to a radial distance of 165,000 kilometers in the morning fringe of the earth's magnetosphere but failed to detect any such electrons during the close encounter with Mars on 14-15 July 1965, at the time when the minimum areocentric radial distance was 13,200 kilometers. This result can mean that the ratio of the magnetic dipole moment of Mars to that of the earth (M(M)/M(E)) is surely less than 0.001 and probably is less than 0.0005. The corresponding upper limits on the equatorial magnetic field at the surface of Mars are 200 and 100 gammas, respectively. It appears possible that the solar wind interacts directly with the Martian atmosphere. PMID- 17747452 TI - Search for Trapped Electrons and a Magnetic Moment at Mars by Mariner IV. AB - The Mariner IV spacecraft on 14-15 July 1965 passed within 9850 kilometers of Mars, carrying a solid-state charged-particle telescope which could detect electrons greater than 40 kiloelectron volts and protons greater than 1 million electron volts. The trajectory could have passed through a bow shock, a transition region, and a magnetospheric boundary where particles could be stably trapped for a wide range of Martian magnetic moments. No evidence of charged particle radiation was found in any of these regions. In view of these results, an upper limit is established for the Martian magnetic moment provided it is assumed that the same physical processes leading to acceleration and trapping of electrons in Earth's magnetic field would be found in a Martian magnetic field. On this basis, the upper limit for the Martian magnetic moment is 0.1 percent that of Earth for a wide range of postulated orientations with respect to the rotational axis of Mars. The implications of these results for the physical and biological environment of Mars are briefly discussed. PMID- 17747453 TI - Zodiacal Dust: Measurements by Mariner IV. AB - Data from the Mariner IV dust-particle experiment reveal an increase by a factor of 5 in the flux of interplanetary dust particles as the heliocentric distance from the sun increases. There is a variation in the slope of the cumulative flux mass distribution, with the steepest slope for the distribution occurring between the planets. No enhancement of the flux in the vicinity of Mars was detected. PMID- 17747454 TI - Magnetic Field Measurements near Mars. AB - During the encounter between Mariner IV and Mars on 14-15 July, no magnetic effect that could be definitely associated with the planet was evident in the magnetometer data. This observation implies that the Martian magnetic dipole moment is, at most, 3 x 10(-4) times that of the earth. PMID- 17747455 TI - Occultation Experiment: Results of the First Direct Measurement of Mars's Atmosphere and Ionosphere. AB - Changes in the frequency, phase, and amplitude of the Mariner IV radio signal, caused by passage through the atmosphere and ionosphere of Mars, were observed immediately before and after occultation by the planet. Preliminary analysis of these effects has yielded estimates of the refractivity and density of the atmosphere near the surface, the scale height in the atmosphere, and the electron density profile of the Martian ionosphere. The atmospheric density, temperature, and scale height are lower than previously predicted, as are the maximum density, temperature, scale height, and altitude of the ionosphere. PMID- 17747456 TI - Right Horn Implantation in the Common Duiker. AB - In the common duiker, Sylvicapra grimmia, implantation occurs only in the right uterine horn, but both ovaries ovulate. PMID- 17747458 TI - Forthcoming Events. PMID- 17747457 TI - Computing Methods Applied to Reactor Problems. PMID- 17747459 TI - Acceleration: Disgrace or Challenge? PMID- 17747460 TI - Effect of Some Sulfhydryl-containing Substances on the Toxicity of an Organic Mercurial Compound. AB - The acute toxicity of an organic mercurial as studied on the mouse, intact anesthetized cat and dog, and the heart-lung preparation of the dog can be readily counteracted by sulfhydryl-containing compounds such as glutathione, cysteine, and 2,3-dimercapto-propanol. Equimolar doses of 2,3-dimercapto-propanol are about five times as active as cysteine or glutathione. PMID- 17747461 TI - The Mechanism of Myotonic Contraction. PMID- 17747462 TI - Biological Incorporation of a Choline Homologue Into Liver Phospholipids. PMID- 17747463 TI - The Effect of Alloxan on the in Vitro Formation of Glucose by the Liver. PMID- 17747464 TI - A Simple and Accurate Soil Fumigant Injection Apparatus. PMID- 17747465 TI - Agar Technique for Arresting Movement in Protozoa. PMID- 17747466 TI - A Spectrophotometric Method for the Determination of p,p'-DDT. PMID- 17747468 TI - Notes on the Results of Army Intelligence Testing in World War I. PMID- 17747467 TI - The Ascorbic Acid Content of Some Malpighia Fruits and Jellies. PMID- 17747469 TI - Embryonic Induction in Regenerating Mesenchyme. PMID- 17747470 TI - Mustard Gas Mutations in Neurospora. PMID- 17747471 TI - This week in science. PMID- 17747472 TI - Science and technology awards. PMID- 17747473 TI - Global warning. PMID- 17747474 TI - Global warning. PMID- 17747475 TI - Global warning. PMID- 17747476 TI - Erratum. AB - In the report "Iron photoreduction and oxidation in an acidic mountain stream" by D. M. McKnight et al. (29 Apr., p. 637), reference 17 [E. L. Madsen, M. D. Morgan, R. E. Good, Limnol. Oceanogr. 31, 382 (1986)] was cited ( p. 638) as indicating "that biological processes are not responsible for light-induced Fe(II) production." This possibility was not addressed by Madsen et al., nor did Madsen et al. use both poisoned and natural streamwater-sediment mixtures to distinguish between biotic and abiotic contributions to iron reduction. In table 1 of the same report, the values in columns two and three were incorrect. They should have been, for sodium, calcium and magnesium, respectively, 2.7 +/- 0.34 mg liter(-1)', 13.0 +/- 0.73 mg liter(-1), and 4.3 +/- 0.24 mg liter(-1). PMID- 17747477 TI - Hazardous waste clean-up. PMID- 17747479 TI - Academy starts news service. PMID- 17747478 TI - Racing After the Z Particle: Stanford's electron-positron collider has been plagued with hardware problems that have foiled efforts to begin exploring the physics of the Z particle. PMID- 17747480 TI - Environmental Awakening in the Soviet Union: Reluctant to admit ecological problems in the past, Soviets are now acknowledging "catastrophic pollution" nationwide. PMID- 17747481 TI - Glasnost: soviet computer lag. PMID- 17747482 TI - NSB Ponders Science Policy Role. PMID- 17747483 TI - Research Psychologists Break with APA. PMID- 17747484 TI - La Nina's Big Chill Replaces El Nino: The cooling of El Nino's unusually warm waters in the Pacific will alter weather and probably cool the "greenhouse," at least temporarily. PMID- 17747485 TI - Superconductivity result unconfirmed. PMID- 17747486 TI - Laser-Cooled Atoms Hit Record Low Temperatures: Carefully tuned lasers now chill atoms to a few millionths of a degree, allowing precise measurements of atomic properties. PMID- 17747487 TI - Climatic changes of the last 18,000 years: observations and model simulations. PMID- 17747488 TI - Hemispherical color differences on pluto and charon. AB - Time-resolved multicolor photometric observations of Pluto-Charon mutual events have been used to derive individual colors for these two bodies and to investigate the degree of color differences between their synchronous facing and opposite hemispheres. Pluto is significantly redder than Charon, where direct measurements of the anti-Charon hemisphere of Pluto and the Pluto-facing hemisphere of Charon yield B-V magnitudes of 0.867 +/- 0.008 and 0.700 +/- 0.010, respectively. Both Pluto and Charon are found to have relatively uniform longitudinal color distributions with lsigma upper limits of 2% and 5%, respectively, for any large-scale hemispherical color asymmetries. Thus, a previous suspicion of a significant color asymmetry on Charon is not confirmed. Instead the data may be attributed to a direct detection of polar caps on Pluto. PMID- 17747489 TI - Effect of a Coordination Change on the Strength of Amorphous SiO2. AB - Measurements of the yield strength of SiO(2) glass to pressures as high as 81 gigapascals at room temperature show that the strength of amorphous silica decreases significantly as it is compressed to denser strctures with higher coordination. Above 27 gigapascals, as the silicon in amorphous SiO(2) is continuously transformed from fourfold to sixfold coordination, the strength of the glass decrases by more than an order of magnitude. These data confirm theoretical predictions that the mechanical properties of polymerized amorphous silicates are sensitive to pressure-induced structural transformations and suggest that the viscosity of silica-rich liquids decreases significantly at high pressures. Such a change in melt rheology could enhance the processes of chemical differentiation with depth in the Earth's mantle. PMID- 17747490 TI - Insensitivity to Ethylene Conferred by a Dominant Mutation in Arabidopsis thaliana. AB - Ethylene influences a number of developmental processes and responses to stress in higher plants. The molecular basis for the action of ethylene was investigated in mutants of Arabidopsis thaliana that have altered responses to ethylene. One mutant line, which has a dominant mutation at a locus designated etr, lacks a number of responses to ethylene that are present in the wild-type plant. These include inhibition of cell elongation, promotion of seed germination, enhancement of peroxidase activity, acceleration of leaf senescence, and feedback suppression of ethylene synthesis by ethylene. These diverse responses, which occur in different tissues of Arabidopsis, appear to share some common element in their transduction pathways-for example, a single receptor for ethylene. Results of ethylene binding experiments in vivo indicate that this receptor may be affected by the etr mutation. PMID- 17747491 TI - A novel target for antidiuretic hormone in insects. AB - Diuresis in insects is controlled by two antagonistic hormone groups: diuretic hormones, which promote water loss, and antidiuretic hormones, which inhibit it. All known antidiuretic factors act solely to promote fluid reabsorption by the hindgut and do not affect secretion by the Malpighian tubules. In the house cricket, Acheta domesticus, an antidiuretic hormone was found that inhibits fluid secretion by the Malpighian tubules but has no effect on the hindgut. Correlations were found between the density of neurosecretory granules and the presence of antidiuretic hormone in the corpora cardiaca, suggesting that the hormone is released from specific axons. Its release is triggered by dehydration; the hormone is detectable in the hemolymph of water-deprived crickets. These results imply that an unusual mechanism regulates water balance in these insects. PMID- 17747492 TI - Third Annual AAAS Colloquium on Science, Arms Control & National Security: Science and Security: Technology and Arms Control for the 1990s. PMID- 17747493 TI - Patterns of weapon development: innovation and the arms race. PMID- 17747494 TI - Neural network programs: explorations in parallel distributed processing. PMID- 17747495 TI - Neutrinos: physics of massive neutrinos. PMID- 17747496 TI - Thermophysiology: tempeature biology of animals. PMID- 17747497 TI - Products & materials. PMID- 17747498 TI - EDWARD CHARLES PICKERING. PMID- 17747499 TI - SOME RECENT CONTRIBUTIONS TO THE PHYSICS OF THE AIR. PMID- 17747500 TI - APPLIED PSYCHOLOGY. PMID- 17747501 TI - THE PUBLICATION OF ISIS. PMID- 17747502 TI - A STEADY CALENDAR. PMID- 17747503 TI - THE GEOLOGICAL SOCIETY OF AMERICA. PMID- 17747504 TI - THE AMERICAN PHYTOPATHOLOGICAL SOCIETY. PMID- 17747505 TI - This week in science. PMID- 17747506 TI - In reply: full disclosure at the university of Florida. PMID- 17747507 TI - Full disclosure at the university of Florida. PMID- 17747509 TI - Global warming questions. PMID- 17747508 TI - Unscrambling an egg. PMID- 17747510 TI - Engineering design. PMID- 17747512 TI - Wolf: my tritium was an impurity. PMID- 17747511 TI - Cold Fusion Conundrum at Texas A&M: The administration's laissez faire response to worries about possible fraud raises questions about the proper balance between academic freedom and the need to guarantee the integrity of research. PMID- 17747513 TI - Amazonian biodiversity. PMID- 17747514 TI - Peer review under review. PMID- 17747515 TI - Soviet missile on display. PMID- 17747516 TI - Third world pollution. PMID- 17747517 TI - Damage to animal research mounts. PMID- 17747518 TI - Voyager's Last Light. PMID- 17747519 TI - Turtle navigation. PMID- 17747520 TI - U. Of Maryland gains from glasnost. PMID- 17747522 TI - Coral pushes back the past. PMID- 17747521 TI - INS Puts Limits on Togetherness. PMID- 17747523 TI - From One Coral Many Findings Blossom: Old coral from drowned Barbados reefs is yielding measures of everything from glacial ice to Earth's magnetic field. PMID- 17747524 TI - 1990 AAAS Philip Hauge Abelson Prize. PMID- 17747525 TI - Axial oxygen-centered lattice instabilities and high-temperature superconductivity. AB - Copper K-edge x-ray absorption data indicate that an axial oxygen-centered lattice instability accompanying the 93 K superconducting transition in YBa(2)Cu(3)O(7) is of a pseudo-(anti)ferroelectric type, in that it appears to involve the softening of a double potential well into a structure in which the difference between the two copper-oxygen distances and the barrier height have both decreased. This softer structure is present only at temperatures within a fluctuation region around the transition. A similar process involving the analogous axial oxygen atom also accompanies the superconducting transition in T1Ba(2)Ca(3)Cu(4)O(11), where the superconducting transition temperature T(c) is ~120 K. The mean square relative displacement of this oxygen atom in YBa(2)Cu(3)O(7) is also specifically affected by a reduction in the oxygen content and by the substitution of cobalt for copper, providing further evidence for the sensitivity of the displacement to additional factors that also influence the superconductivity. On the basis of the implied coupling of this ionic motion to the superconductivity, a scenario for high-temperature superconductivity is presented in which both phonon and electronic (charge transfer) channels are synergistically involved. PMID- 17747526 TI - North-South contraction of the mojave block and strike-slip tectonics in southern california. AB - The Mojave block of southern California has undergone significant late Cenozoic north-south contraction. This previously unappreciated deformation may account for part of the discrepancy between neotectonic and plate-tectonic estimates of Pacific-North American plate motion, and for part of the Big Bend in the San Andreas fault. In the eastern Mojave block, contraction is superimposed on early Miocene crustal extension. In the western Mojave block, contractional folds and reverse faults have been mistaken for extensional structures. The three dimensional complexity of the contractional structures may mean that rigid-block tectonic models of the region based primarily on paleomagnetic data are unreliable. PMID- 17747527 TI - Correlated Evolution of Female Mating Preferences and Male Color Patterns in the Guppy Poecilia reticulata. AB - Sexual selection may explain why secondary sexual traits of males are so strongly developed in some species that they seem maladaptive. Female mate choice appears to favor the evolution of conspicuous color patterns in male guppies (Poecilia reticulata) from Trinidad, but color patterns vary strikingly among populations. According to most theory, correlated evolution of female mating preferences and preferred male traits within populations could promote this kind of divergence between populations. But mating preferences could also constrain the evolution of male traits. In some guppy populations, females discriminate among males based on variation in the extent of orange pigment in male color patterns, and populations differ significantly in the degree offemale preferences for orange area. In a comparison ofseven populations, the degree offemale preference based on orange is correlated with the population average orange area. Thus male traits and female preferences appear to be evolving in parallel. PMID- 17747528 TI - The Invisible Work Force. Transforming American Business with Outside and Home Based Workers. Beverly Lozano. Free Press (Macmillan), New York, 1989. xii, 218 pp. $19.95. PMID- 17747529 TI - Behind the Factory Walls. Decision Making in Soviet and US Enterprises. Paul R. Lawrence, Charalambos A. Vlachoutsicos, and six others. Harvard Business School Press, Boston, 1990. xii, 342 pp., $29.95. PMID- 17747532 TI - Products & materials. PMID- 17747530 TI - Flight Strategies of Migrating Hawks. Paul Kerlinger. University of Chicago Press, Chicago, 1989. xvi, 375 pp., illus. $60; paper, $19.95. PMID- 17747533 TI - Publicity Needs of NIH. PMID- 17747535 TI - Student Motivation. PMID- 17747534 TI - Identifying Epithets. PMID- 17747537 TI - Broader Outlook for Research. PMID- 17747536 TI - Letters to the Editor. PMID- 17747538 TI - The New versus the Classical in Science. PMID- 17747540 TI - Neutrinos, Old and New. PMID- 17747541 TI - Graduate Education: Navy Program in Rocket Astronomy Opens New Horizons to University Scientists. PMID- 17747539 TI - Cloud Patterns over Tropical Oceans. PMID- 17747542 TI - Mental Health: House Committee Cuts Funds Proposed by Kennedy. PMID- 17747543 TI - Antibiotics: Experts Question Value in Treating Colds; FDA Issues Ban on Use in Compounds. PMID- 17747544 TI - Historical Chronology. PMID- 17747545 TI - West Ford Dipole Belt: Optical Detection at Palomar. AB - Optical detection of the West Ford orbiting dipole belt was accomplished on at least four occasions during the second week in May 1963. The maxi-mum surface brightness was about 4 percent of the night sky radiation at an effective wavelength of lambda = 4400 A The density of the belt has evidently decreased because it was not detected in a second observation period during the third week in June. PMID- 17747546 TI - West Ford Dipole Belt: Photometric Observations. AB - Photoelectric observations of the West Ford belt of copper dipoles covering the period from I week to I month after the launching show a feature considerably wider than the announced belt width. The present belt is not injurious to astronomical observatations from the ground but it could seriously aflect observations made from low-orbiting satellite systems. Much stronger belts would seriously interfere with astronomical observations. PMID- 17747547 TI - Infrared Spectra of Hydronium Ion in Micaceous Minerals. AB - X-ray diffraction measurements of the d((001)) spacing and the infrared absorption spectra of hydrogensaturated saturated micas show that an ion of approximately the same size and properties as hydronium is present and gives a unique absorption band at about 3470 cm(-1). PMID- 17747548 TI - Size Distributions of Sedimentary Populations. AB - Separate sedimentary populations are not all characterized by lognormal size distributions. Populations of different sizes of material are produced by different mechanisms of abrasion: pebbles and gravel by singlestage crushing; sand by repeated abrasion; and silt and clay by chipping from larger grains. Each mechanism imposes a different size distribution on the product. PMID- 17747549 TI - Infrared Radiation from the Atmosphere over the Arctic Ocean. AB - The emission spectrum of the atmosphere over the Arctic Ocean was observed during a period when atmosphere and snow surface temperatures were about -40 degrees C. The main contributions to the emission in the 5-to 21-micron range came from ozone and carbon dioxide, with water vapor playing a minor part. PMID- 17747550 TI - Confirmation of the Crystal Structure of Tetrahedrite, Cu12Sb4S13. AB - The crystal structure of tetrahedrite, proposed in 1934 by Pauling and Neuman, has been confirmed. Least-squares refinement reduced the initial disagreement factor from 27.9 to 4.9 percent. Antimony displays three short orthogonal bonds to sulfur atoms. Two types of copper are tetrahedrally and triangularly coordinated by sulfur, respectively. PMID- 17747552 TI - Genesis of Hydrocarbons of Low Molecular Weight in Organic-Rich Aquatic Systems. AB - Mild heat treatment of water-wet marine muds resulted in the genesis of three aromatic hydrocarbons characteristic of crude oils, but which are seldom found in significant quantities in recent sediments. Whereas part of the toluene and xylenes may have stemmed from carotenoid pigments, the source of the benzene as well as the larger amount of the toluene and xylene is as yet unknown. PMID- 17747551 TI - Photochemical Generation of the Hydrated Electron. AB - A transient species with properties similar to the hydrated electron produced previously by electron irradiation has been observed by flash photolysis of aqueous solutions of inorganic salts and aromatic compounds including amino acids. PMID- 17747553 TI - Varying Sensitivity of C57BL/Crgl Mice to Grouping. AB - Mice responded differentially to increases in population size, depending on their prior experience. Compared to animals grouped prior to an increase in population size, animals housed as isolates responded to grouping with more fighting, a greater diminuation of testis weight, and a higher level of locomotor activity. They also had lower testis weight and higher locomotor activity than individually housed, nongrouped controls. PMID- 17747554 TI - Air Pollution and Medical Research. PMID- 17747555 TI - Electron Microscopy: Proteins in Experimental Pathology. PMID- 17747556 TI - Root Diseases Biologically Controlled. PMID- 17747557 TI - Forthcoming Events. PMID- 17747559 TI - Aptitude Tests. PMID- 17747558 TI - Foreign Trade in Scientific Instruments. PMID- 17747560 TI - Subnuclear Particles: A Question of Social Priorities. PMID- 17747561 TI - Theory and Hypothesis. PMID- 17747562 TI - Letters to the Editor. PMID- 17747563 TI - Letters to the Editor. PMID- 17747564 TI - Letters to the Editor. PMID- 17747565 TI - Distribution of U. S. Scientific Literature. PMID- 17747567 TI - HEW: As Secretary of Department of Health, Education and Welfare Gardner Faces Formidable Tasks. PMID- 17747566 TI - Field Ion Microscopy. PMID- 17747568 TI - Administration on Aging: New HEW Unit Will Offer Grants to States, Universities for Studies of Aging. PMID- 17747569 TI - Mariner IV Photography of Mars: Initial Results. AB - The 22 photographs of Mars taken by Mariner IV have been successfully received on earth. The Martian surface photographed is rather densely populated with impact craters whose sizes range up to at least 120 kilometers in diameter. We infer that the visible Martian surface is extremely old and that neither a dense atmosphere nor oceans have been present on the planet since the cratered surface was formed. PMID- 17747570 TI - Rock Degradation by Alkali Metals: A Possible Lunar Erosion Mechanism. AB - When rocks melt under ultrahigh-vacuum conditions, their alkali components volatilize as metals. These metal vapors act to comminute polycrystalline rocks to their component minerals. The resultant powder is porous and loosely packed and its characteristics may be compatible with the lunar surface as revealed by the Ranger photographs. If meteorite impact or lunar volcanism has produced vaporization or areas of molten lava, alkali erosion may have given dust of this character in adjacent solid areas. PMID- 17747571 TI - Stability of Lakes near the Temperature of Maximum Density. AB - In deep lakes that are near the temperature of maximum density, stability is greatest when the decrease of temperature with depth is about one-half of the decrease in temperature of maximum density with depth. Observed temperature decreases in lakes under such conditions tend to follow the curve that produces greatest stability. PMID- 17747572 TI - Dengue Type 2 Virus in Naturally Infected Aedes albopictus Mosquitoes in Singapore. AB - A strain of dengue type 2 virus has been isolated from Aedes albopictus collected in Singapore. This is the first report of a natural isolation of dengue virus from this species, which has long been suspected as a vector in nature. PMID- 17747573 TI - Reduction-like Effect of Carbohydrates on Cytochrome c. AB - Certain carbohydrates cause changes in the absorption spectrum of cytochrome c; these changes are the same as those accompanying conversion from the oxidized to the reduced form. Various carbohydrates are compared by measuring changes in absorbance at a characteristic wavelength. PMID- 17747574 TI - Aggressive Mimicry in Photuris: Firefly Femmes Fatales. AB - Firefly females of the genus Photuris, long known to be carnivorous, attract and devour males of the genus Photinus by mimicking the flash-responses of Photinus females. Although suspected, this behavior had not been observed previously. PMID- 17747575 TI - Tektites: Origin of Parent Material. PMID- 17747576 TI - Wright Valley: Conjectural Volcanoes. PMID- 17747578 TI - Deep-Sea Stratigraphy. PMID- 17747577 TI - Kinins, Cytokinins, Phytokinins. PMID- 17747579 TI - Forthcoming Events. PMID- 17747580 TI - SOME RECENT AMERICAN PAPERS IN COMPARATIVE ANATOMY. PMID- 17747581 TI - ON THE CONSTITUTION OF THE NAPHTALINES AND THEIR DERIVATIVES. PMID- 17747582 TI - NATIONAL ACADEMY OF SCIENCES. PMID- 17747583 TI - THE BRAIN OF THE ORANG. PMID- 17747584 TI - CAUSES WHICH DETERMINE, THE PROGRES. SIVE MOVEMENT OF STORMS. PMID- 17747586 TI - Alvan Clark & Sons. PMID- 17747587 TI - COMET DISCOVERED. PMID- 17747585 TI - To the Editor of Science. PMID- 17747588 TI - ASTRONOMY: THE TEMPLEL-SWIFT COMET. PMID- 17747589 TI - To the Editor of Science. PMID- 17747590 TI - CHEMICAL NOTES. PMID- 17747591 TI - THE ROYAL SOCIETY. PMID- 17747592 TI - To the Editor of "Science". PMID- 17747593 TI - SOCIETY OF AMERICAN TAXIDERMISTS. PMID- 17747594 TI - SCIENCE NEWS. PMID- 17747595 TI - THE MEDICAL SCIENCES. PMID- 17747597 TI - THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17747596 TI - THE VIRTUE OF MEDICINE AS A PROFESSION. PMID- 17747598 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17747599 TI - THE VELOCITY OF GRAVITATION. PMID- 17747600 TI - "PINK-ROOT" OF ONIONS CAUSED BY PHOMA SP. PMID- 17747601 TI - THALLIUM AS AN INSECTICIDE. PMID- 17747603 TI - A CONVENIENT METHOD FOR FEEDING PLANARIANS. PMID- 17747602 TI - NOTE ON THE SCIENTIFIC METHOD AND AUTHORITY. PMID- 17747605 TI - STUDY ON SUGAR CANE MOSAIC. PMID- 17747606 TI - THE NATIONAL ACADEMY OF SCIENCES. PMID- 17747604 TI - SERIES RELATIONS IN THE FIRST LONG PERIOD. PMID- 17747607 TI - POST-LARVAL LOBSTERS. PMID- 17747608 TI - Erratum. AB - In the report by E. T. Walters,. T. J. Carew, and E. R. Kandel (30 Jan., p. 504), labels (B) and (C) of Fig. 1 were inadvertently reversed. Figure 1B should be "Siphon withdrawal," and Fig. 1C should be "Inking." PMID- 17747609 TI - Evolutionary confusion? PMID- 17747611 TI - U.s. Derails energy plan for third world. PMID- 17747610 TI - National Science Foundation's Other Mission. PMID- 17747612 TI - Novel help for the handicapped. PMID- 17747613 TI - How to keep your shirt--if you put it in genes. PMID- 17747614 TI - Littlewood conjecture resolved. PMID- 17747615 TI - Advance in integer programming. PMID- 17747616 TI - Russian proves van der warden conjecture. PMID- 17747617 TI - New chemicals promise larger crops. PMID- 17747618 TI - Degree completion by women and minorities in sciences increases. PMID- 17747620 TI - Foreign Graduate Students Attend AAAS Meetings. PMID- 17747619 TI - Energy needs of northeast tribes subject of seminar. PMID- 17747622 TI - Obituaries. PMID- 17747621 TI - Puerto rican scientists to meet in washington. PMID- 17747623 TI - Report from Indian science congress. PMID- 17747624 TI - SWARM Announces Its Spring Meeting. PMID- 17747625 TI - Mass concentration. PMID- 17747626 TI - Technological choices. PMID- 17747627 TI - Wintering birds. PMID- 17747628 TI - Populations in motion. PMID- 17747629 TI - Calibration of the beginning of the age of mammals in patagonia. AB - Beds of the Rio Chico Formation containing the earliest known land mammals in Patagonia, southern Argentina, were calibrated by potassium-argon age determinations and paleomagnetic polarity data. The Riochican land mammal age encompasses the middle and late Paleocene and corresponds in time with Torrejonian and Tiffanian land mammal faunas in North America. PMID- 17747630 TI - Discovery of natural gain amplification in the 10-micrometer carbon dioxide laser bands on Mars: a natural laser. AB - Fully resolved intensity profiles of various lines in the carbon dioxide band at 10.4 micrometers have been measured on Mars with an infrared heterodyne spectrometer. Analysis of the line shapes shows that the Mars atmosphere exhibits positive gain in these lines. The detection of natural optical gain amplification enables identification of these lines as a definite natural laser. PMID- 17747631 TI - Eicosapentaenoic and Arachidonic Acids from Phytophthora infestans Elicit Fungitoxic Sesquiterpenes in the Potato. AB - Mycelial extracts from Phytophthora infestans caused necrosis and elicited the accumulation of antimicrobial stress metabolites in potato tubers. A portion of the material with elicitor activity could be extracted from the mycelium by a mixture of chloroform and methanol. The most active elicitors of stress metabolites in these extracts were eicosapentaenoic and arachidonic acids. These fatty acids were found in either free or esterified form in all active fractions of the mycelial extracts. PMID- 17747632 TI - Geotropism in corn roots: evidence for its mediation by differential Acid efflux. AB - The elongation zone in intact growing corn roots secretes acid leading to a reduced pH along the surface of the root and in the adjacent medium. This can be detected by placing the root on an agar medium containing the pH indicator dye bromocresol purple. When the root is treated with a growth inhibitory concentration of the hormone indole-3-acetic acid, the acid efflux is reversed and growth is greatly retarded. When the root is mounted vertically, acid secretion is uniform along the elongation zone, and the root grows straight downward. When the root is placed horizontally, there is enhanced acid efflux along the upper surface of the elongation zone and reduced acid efflux along the lower surface. An increased rate of elongation of the upper cells relative to the lower cells then results in downward curvature of the root. The correlation between acid efflux patterns and growth patterns indicates that proton efflux is important in the control of root growth. PMID- 17747633 TI - Pheromonal control of dealation and oogenesis in virgin queen fire ants. AB - In the fire ant Solenopsis invicta, sexually mature virgin females are prevented from shedding their wings and becoming functional egg layers by the presence of the mated queen. Experimental data suggest that this inhibitory effect results from the action of a relatively nonvolatile primer pheromone (or pheromones) produced by the mated queen and distributed by the workers. Target ants are both virgin queens and workers. PMID- 17747634 TI - Genetic basis of migratory behavior in European warblers. AB - The seasonal course and magnitude of migratory restlessness recorded in four populations of the blackcap Sylvia atricapilla differ in a population-specific fashion that is related to the distance of travel. Experimentally produced hybrids of an exclusively migratory European population and a partially migratory African population showed intermediate migratory restlessness and an intermediate percentage of birds displaying restlessness compared to the two parental stocks. These results demonstrate the genetic basis of migratory behavior in this avian species and support the hypothesis that partial migration of populations is due to polymorphism. PMID- 17747635 TI - Dominance hierarchies in leptothorax ants. AB - The social organization of Leptothorax allardycei is unique among ant species thus far studied. The workers form linear dominance hierarchies characterized by routine displays of dominance, avoidance behavior, and even fighting. The high ranking ants are favored in liquid food exchange, have greater ovarian development, and produce 20 percent of the eggs. PMID- 17747636 TI - This week in science. PMID- 17747637 TI - Corrections and clarifications. AB - In the report "DNA sequence determination by hybridization: A strategy for efficient large-scale sequencing" by R. Drmanac et al. (11 June, p. 1649), the sequence of clone 8 in figure 2B (p. 1650) was inadvertently shortened by the deletion of "GA" at the seventh position from the right in the second line. In reference 20 of the same report, the probes ATATGGGG and ATGTCCTG should not have been included. PMID- 17747638 TI - Genetics and violent crime. PMID- 17747639 TI - Sciencescope. PMID- 17747641 TI - The grim reaper plays by quirky rules. PMID- 17747640 TI - A strategic message from mikulski. PMID- 17747642 TI - Nurturing new entrepreneurs. PMID- 17747643 TI - El nino says adios, as computers predicted. PMID- 17747644 TI - Did early humans reach siberia 500,000 years ago? PMID- 17747645 TI - Inertia: does empty space put up the resistance? PMID- 17747646 TI - Math Attendees Find There's Life After Fermat Proof. AB - The uncertain status of the recent proof of Fermat's Last Theorem (Science, 24 December 1993, p. 1967) was the hot topic in the hallways at the joint meetings of the American Mathematical Society and the Mathematical Association of America, held 12-15 January in Cincinnati. But a few other topics did manage to get discussed. Among them: How gambling pays off in computing the volume of high dimensional shapes; how a mathematical description of water dripping down a window pane might lead to the design of digital pulses that could race through the optical fibers of the future; and how one can be fooled infinitely often by another theorem of Fermat's. PMID- 17747647 TI - Science after the cold war. PMID- 17747648 TI - Researchers Sift the Ashes of SDI. PMID- 17747649 TI - SDI's Mixed Legacy for the Free-Electron Laser. PMID- 17747650 TI - A debut for star wars' darling, clementine. PMID- 17747651 TI - The defense department declassifies the Earth-slowly. PMID- 17747652 TI - Nonproliferation boom gives a lift to the national labs. PMID- 17747653 TI - No easy way to shackle the nuclear demon. PMID- 17747654 TI - Pork and plutonium may not mix. PMID- 17747655 TI - Nuclear test ban monitoring: new requirements, new resources. PMID- 17747656 TI - Toward new multi-property materials. PMID- 17747657 TI - Verification, validation, and confirmation of numerical models in the Earth sciences. AB - Verification and validation of numerical models of natural systems is impossible. This is because natural systems are never closed and because model results are always nonunique. Models can be confirmed by the demonstration of agreement between observation and prediction, but confirmation is inherently partial. Complete confirmation is logically precluded by the fallacy of affirming the consequent and by incomplete access to natural phenomena. Models can only be evaluated in relative terms, and their predictive value is always open to question. The primary value of models is heuristic. PMID- 17747658 TI - A magnetohydrodynamic model of solar wind interaction with asteroid gaspra. AB - The solar wind response to a small-sized magnetized body is modeled on the basis of a two-dimensional magnetohydrodynamic (MHD) plasma description including Hall current corrections (Hall-MHD model). Basic features of the magnetic signatures observed near Galileo's closest approach to asteroid Gaspra are reproduced, assuming Gaspra's magnetic dipole momentto be of the order of 10(14) ampere.meters squared and tilted to the solar wind flow direction at an angle of about 45 degrees . PMID- 17747659 TI - Stilbazolium-MPS3 Nanocomposites with Large Second-Order Optical Nonlinearity and Permanent Magnetization. AB - Intercalated layered materials comprising an organic dye and inorganic MPS(3) [where M is either the manganese ion (Mn(2+)) or the cadmium ion (Cd(2+))] phases have been prepared. The intercalation process induces a spontaneous poling, giving rise to an efficiency of 750 times that of urea in second-harmonic generation for the cadmium derivative. In addition, the manganese derivative displays a permanent magnetization below 40 kelvin. Thus, these materials exhibit both a large optical nonlinearity and magnetic ordering. PMID- 17747660 TI - Paleoindians in beringia: evidence from arctic alaska. AB - Excavations at the Mesa site in arctic Alaska provide evidence for a Paleoindian occupation of Beringia, the region adjacent to the Bering Strait. Eleven carbon 14 dates on hearths associated with Paleoindian projectile points place humans at the site between 9,730 and 11,660 radiocarbon years before present (years B.P.). The presence of Paleoindians in Beringia at these times challenges the notion that Paleoindian cultures arose exclusively in mid-continental North America. The age span of Paleoindians at the Mesa site overlaps with dates from two other cultural complexes in interior Alaska. A hiatus in the record of human occupation occurs between 10,300 and 11,000 years B.P. Late Glacial climatic fluctuations may have made northern Alaska temporarily unfavorable for humans and spurred their southward dispersal. PMID- 17747661 TI - Tropical temperature variations since 20,000 years ago: modulating interhemispheric climate change. AB - Tropical sea surface temperatures (SSTs), as thermodynamically recorded in Barbados corals, were 5 degrees C colder than present values 19,000 years ago. Variable tropical SSTs may explain the interhemispheric synchroneity of global climate change as recorded in ice cores, snowline reconstructions, and vegetation records. Radiative changes due to cloud type and cloud cover are plausible mechanisms for maintaining cooler tropical SSTs in the past. PMID- 17747662 TI - Lake-atmosphere feedbacks associated with paleolakes bonneville and lahontan. AB - A high-resolution, regional climate model nested within a general circulation model was used to study the interactions between the atmosphere and the large Pleistocene lakes in the Great Basin of the United States. Simulations for January and July 18,000 years ago indicate that moisture provided by synoptic scale atmospheric circulation features was the primary component of the hydrologic budgets of Lakes Lahontan and Bonneville. In addition, lake-generated precipitation was a substantial component of the hydrologic budget of Lake Bonneville at that time. This local lake-atmosphere interaction may help explain differences in the relative sizes of these lakes 18,000 years ago. PMID- 17747663 TI - Envisioning a quantum supercomputer. PMID- 17747664 TI - An envisioning of consciousness. PMID- 17747665 TI - Biomedical progenitor. PMID- 17747666 TI - "Spandrels" dissected. PMID- 17747667 TI - Vignette: in mid-history. PMID- 17747669 TI - Products & materials. PMID- 17747668 TI - Quantum technology. PMID- 17747670 TI - SCIENCE NEWS. PMID- 17747671 TI - CHEMICAL MEDIATORS OF AUTONOMIC NERVE IMPULSES. PMID- 17747672 TI - HIGH VOLTAGE. II. PMID- 17747673 TI - AN EXPLANATION OF THE CAUSE OF SPIRAL GRAIN IN TREES. PMID- 17747674 TI - OBSERVATION OF A NEW MEXICO METEOR FROM THE AIR. PMID- 17747676 TI - PUNISHMENT AND REWARD IN LEARNING. PMID- 17747675 TI - THE POISONING OF FISH. PMID- 17747678 TI - INVESTIGATIONS IN PUERTO RICO ON MANSON'S BLOOD-FLUKE INFECTION (SCHISTOSOMIASIS MANSONI). PMID- 17747677 TI - A PHOTOGRAPHIC TECHNIQUE FOR THE STUDY OF EXTENSIVE DATA ON SMALL POPULATIONS. PMID- 17747679 TI - AN IMPROVED CAPILLARY MERCURY VAPOR LAMP. PMID- 17747681 TI - PRELIMINARY NOTE ON THE STRUCTURE OF ASCORBIC ACID (VITAMIN C). PMID- 17747680 TI - TRANSMISSION OF INFECTIOUS EQUINE ENCEPHALOMYELITIS IN MAMMALS AND BIRDS. PMID- 17747682 TI - THE INTERNAL CONSTITUTION OF THE STARS. PMID- 17747684 TI - JOHN LOSSEN PRICER. PMID- 17747683 TI - THE HAWAIIAN OLONA. PMID- 17747685 TI - FRANK SLATER DAGGETT. PMID- 17747687 TI - A NEW VARIETY OF THE ROOF RAT. PMID- 17747686 TI - A BAND SPECTRUM FROM MERCURY VAPOR. PMID- 17747688 TI - ANOTHER CORN SEED PARASITE. PMID- 17747689 TI - A STAND FOR THE BARBOUR MICRODIS-SECTION APPARATUS. PMID- 17747690 TI - GASTRIC RESPONSE TO FOODS. PMID- 17747691 TI - THE AMERICAN CHEMICAL SOCIETY. VI. PMID- 17747692 TI - THE PLACE OF STATE ACADEMIES OF SCIENCE AMONG SCIENTIFIC ORGANIZATIONS. PMID- 17747693 TI - THE SAFEGUARDING OF NATIONAL PARKS. PMID- 17747694 TI - SCIENCE AND RELIGION. PMID- 17747695 TI - THE STATUS OF PUEBLO INDIAN LANDS. PMID- 17747696 TI - THE LIFE AND SERVICES OF PROFESSOR JOHN TROWBRIDGE. PMID- 17747698 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17747697 TI - DYE SOLUBILITY IN RELATION TO STAINING SOLUTIONS. PMID- 17747699 TI - "THE NEW AIR WORLD". PMID- 17747700 TI - FURTHER NOTES ON THE "WINTER CYCLE" IN THE DOMESTIC FOWL. PMID- 17747701 TI - THE UTILIZATION OF ATMOSPHERIC NITROGEN BY SACCHAROMYCES CEREVISIAE. PMID- 17747702 TI - THE AMERICAN CHEMICAL SOCIETY. PMID- 17747703 TI - THE STORY OF COSMOLOGICAL THEORY. PMID- 17747704 TI - WORK OF THE DEPARTMENT OF AGRICULTURE. PMID- 17747705 TI - A TEXAS METEOR. PMID- 17747706 TI - ON THE COLLOID CHEMISTRY OF FEHLING'S TEST. PMID- 17747707 TI - WHY CHLOROFORM IS A MORE POWERFUL AND DANGEROUS ANESTHETIC THAN ETHER. PMID- 17747708 TI - THE AMERICAN ASSOCIATION OF VARIABLE STAR OBSERVERS. PMID- 17747709 TI - BOSTON MEETING OF THE AMERICAN CHEMICAL SOCIETY. IV. PMID- 17747710 TI - COMMENT AND CRITICISM. PMID- 17747711 TI - An open polar sea. PMID- 17747713 TI - The Ohio earthquake. PMID- 17747712 TI - The steep slopes of the western loess. PMID- 17747714 TI - Discrediting American science. PMID- 17747715 TI - THE WORK OF OCTAVE HALLAUER. PMID- 17747716 TI - THE SYNOPTICAL FLORA OF NORTH AMERICA. PMID- 17747718 TI - THE AMERICAN HISTORICAL ASSOCIATION. PMID- 17747717 TI - THE LANGUAGES OF AFRICA. PMID- 17747719 TI - ASSOCIATION OF OFFICIAL AGRICULTURAL CHEMISTS OF THE UNITED STATES. PMID- 17747720 TI - NOTES ON THE ELECTRICAL CONFERENCE. PMID- 17747721 TI - BRITISH ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17747722 TI - COMMENT AND CRITICISM. PMID- 17747723 TI - THE COAST AND GEODETIC SURVEY. PMID- 17747724 TI - THE ABBOTT COLLECTION AT THE PEABODY MUSEUM. PMID- 17747725 TI - RECENT CHANGES IN CORNELL UNIVERSITY. PMID- 17747726 TI - FIRST LESSONS IN PHILOSOPHY. PMID- 17747727 TI - WASHINGTON LETTER. PMID- 17747728 TI - The temperature of the moon. PMID- 17747729 TI - A waste of public money. PMID- 17747730 TI - LETTERS TO THE EDITOR. PMID- 17747731 TI - Sir William Thomson to the coefficients. PMID- 17747732 TI - The Davenport tablet. PMID- 17747733 TI - A new meteoric iron from West Virginia. PMID- 17747734 TI - Dr. Otto Meyer and the south-western tertiary. PMID- 17747735 TI - LETTERS TO THE EDITOR. PMID- 17747737 TI - Equatorial currents in star and planetary atmospheres. PMID- 17747736 TI - A national university. PMID- 17747738 TI - Some points in the evolution of the horses. PMID- 17747739 TI - The English sparrow. PMID- 17747740 TI - Congenital deaf-mutism. PMID- 17747741 TI - NATIONAL ACADEMIES AND THE PROGRESS OF RESEARCH. PMID- 17747742 TI - THE PLAN OF WORK IN CONNECTION WITH A NEW MARINE LABORATORY ON THE PACIFIC. PMID- 17747743 TI - WINSLOW UPTON. PMID- 17747744 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17747745 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17747746 TI - WHAT WAS THE CAUSE OF THE ESKERS? PMID- 17747747 TI - MATTER AND MEMORY. PMID- 17747748 TI - A MISNAMED PORTRAIT OF JOHN SHAW BILLINGS. PMID- 17747749 TI - A SECOND OCCURRENCE OF ICHTHYOSURIAN REMAINS IN THE BENTON CRETACEOUS. PMID- 17747750 TI - LAG AND LEAD WITH A BRAUN TUBE. PMID- 17747751 TI - A NOTE ON SEX DETERMINATION. PMID- 17747752 TI - THE FEDERATION OF AMERICAN SOCIETIES FOR EXPERIMENTAL BIOLOGY. PMID- 17747753 TI - THE AMERICAN SOCIETY OF BIOLOGICAL CHEMISTS. PMID- 17747754 TI - THE AMERICAN ASSOCIATION OF ECONOMIC ENTOMOLOGISTS. PMID- 17747756 TI - THE SOUTHERN SOCIETY FOR PHILOSOPHY AND PSYCHOLOGY. PMID- 17747755 TI - THE AMERICAN PHILOSOPHICAL ASSOCIATION. PMID- 17747757 TI - TM: Meditation or Sleep? PMID- 17747758 TI - Doomsday expectations. PMID- 17747759 TI - Viking 1. PMID- 17747760 TI - Energy partitioning in the products of ionic decomposition. PMID- 17747761 TI - Ecologic dilemmas. PMID- 17747762 TI - Nuclear Explosives: Technology for On-site Inspection. PMID- 17747763 TI - Cosmetic standards: are pesticides overused for appearances sake? PMID- 17747764 TI - Checking on nuclear blasts. PMID- 17747765 TI - Science adviser installed. PMID- 17747766 TI - Entomologists Vote to Join CAST. PMID- 17747767 TI - Biomedical training: time for a slowdown. PMID- 17747768 TI - Energy conservation: congress acts on building standards. PMID- 17747769 TI - Coal Research (II): Gasification Faces an Uncertain Future. PMID- 17747770 TI - Questioning the synthetic fuels option. PMID- 17747771 TI - A fancier of Mars. PMID- 17747772 TI - Coastal cultures. PMID- 17747773 TI - Drug actions in bacteria. PMID- 17747774 TI - Regulation of viruses. PMID- 17747775 TI - Membrane systems. PMID- 17747776 TI - The first viking mission to Mars. PMID- 17747777 TI - Preliminary results from the viking orbiter imaging experiment. AB - During its first 30 orbits around Mars, the Viking orbiter took approximately 1000 photographic frames of the surface of Mars with resolutions that ranged from 100 meters to a little more than 1 kilometer. Most were of potential landing sites in Chryse Planitia and Cydonia and near Capri Chasma. Contiguous high resolution coverage in these areas has led to an increased understanding of surface processes, particularly cratering, fluvial, and mass-wasting phenomena. Most of the surfaces examined appear relatively old, channel features abound, and a variety of features suggestive of permafrost have been identified. The ejecta patterns around large craters imply that fluid flow of ejecta occurred after ballistic deposition. Variable features in the photographed area appear to have changed little since observed 5 years ago from Mariner 9. A variety of atmospheric phenomena were observed, including diffuse morning hazes, both stationary and moving discrete white clouds, and wave clouds covering extensive areas. PMID- 17747778 TI - Viking: Mars atmospheric water vapor mapping experiment--preliminary report of results. AB - Observations made from the Viking I orbiter show very little water vapor in the Mars atmosphere in the southern hemisphere (0 to 3 precipitable micrometers) with a gradual increase across the equator to northern latitudes. Maximum amounts between 20 and 30 micrometers have been observed in the short period covered by the observations to date. The season, northern midsummer, corresponds to the beginning of the water vapor cycle in that hemisphere. A strong repetitive diurnal cycling between the solid and vapor phases is observed at a site to the east of the Tharsis Ridge at 10 degrees north latitude; the vapor lies close to the martian surface and is most probably in saturation equilibrium with a surface haze or fog throughout much of the day. PMID- 17747779 TI - Infrared thermal mapping of the martian surface and atmosphere: first results. AB - The Viking infrared thermal mapper measures the thermal emission of the martian surface and atmosphere and the total reflected sunlight. With the high resolution and dense coverage being achieved, planetwide thermal structure is apparent at large and small scales. The thermal behavior of the best-observed areas, the landing sites, cannot be explained by simple homogeneous models. The data contain clear indications for the relevance of additional factors such as detailed surface texture and the occurrence of clouds. Areas in the polar night have temperatures distinctly lower than the CO(2) condensation point at the surface pressure. This observation implies that the annual atmospheric condensation is less than previously assumed and that either thick CO(2) clouds exist at the 20 kilometer level or that the polar atmosphere is locally enriched by noncondensable gases. PMID- 17747781 TI - Preliminary meteorological results on Mars from the viking 1 lander. AB - The results from the meteorology instruments on the Viking 1 lander are presented for the first 4 sols of operation. The instruments are working satisfactorily. Temperatures fluctuated from a low of 188 degrees K to an estimated maximum of 244 degrees K. The mean pressure is 7.65 millibars with a diurnal variation of amplitude 0.1 millibar. Wind speeds averaged over several minutes have ranged from essentially calm to 9 meters per second. Wind directions have exhibited a remarkable regularity which may be associated with nocturnal downslope winds and gravitational oscillations, or to tidal effects of the diurnal pressure wave, or to both. PMID- 17747780 TI - Composition and structure of the martian atmosphere: preliminary results from viking 1. AB - Results from the aeroshell-mounted neutral mass spectrometer on Viking I indicate that the upper atmosphere of Mars is composed mainly of CO(2) with trace quantities of N(2), Ar, O, O(2), and CO. The mixing ratios by volume relative to CO(2) for N(2), Ar, and O(2) are about 0.06, 0.015, and 0.003, respectively, at an altitude near 135 kilometers. Molecular oxygen (O(2)(+)) is a major component of the ionosphere according to results from the retarding potential analyzer. The atmosphere between 140 and 200 kilometers has an average temperature of about 180 degrees +/- 20 degrees K. Atmospheric pressure at the landing site for Viking 1 was 7.3 millibars at an air temperature of 241 degrees K. The descent data are consistent with the view that CO(2) should be the major constituent of the lower martian atmosphere. PMID- 17747782 TI - The surface of Mars: there view from the viking 1 lander. AB - The first photographs ever returned from the surface of Mars were obtained by two facsimile cameras aboard the Viking 1 lander, including black-and-white and color, 0.12 degrees and 0.04 degrees resolution, and monoscopic and stereoscopic images. The surface, on the western slopes of Chtyse Planitia, is a boulder strewn deeply reddish desert, with distant eminences-some of which may be the rims of impact craters-surmounted by a pink sky. Both impact and aeolian processes are evident. After dissipation of a small dust cloud stirred by the landing maneuvers, no subsequent signs of movement were detected on the landscape, and nothing has been observed that is indicative of macroscopic biology at this time and place. PMID- 17747783 TI - Composition of the atmosphere at the surface of Mars: detection of argon-36 and preliminary analysis. AB - The composition of the martian atmosphere was determined by the mass spectrometer in the molecular analysis experiment. The presence of argon and nitrogen was confirmed and a value of 1 to 2750 +/- 500 for the ratio of argon-36 to argon-40 was established. A preliminary interpretation of these results suggests that Mars had a slightly more massive atmosphere in the past, but that much less total outgassing has occurred on Mars than on Earth. PMID- 17747784 TI - Viking lander location and spin axis of Mars: determination from radio tracking data. AB - Radio tracking data from the Viking lander have been used to determine the lander position and the orientation of the spin axis of Mars. The areocentric coordinates of the lander are 22.27 degrees N, 48.00 degrees W, and 3389.5 kilometers from the center of mass; the spin axis orientation, referred to Earth's mean equator and equinox of 1950.0, is 317.35 degrees right ascension and 52.71 degrees declination. PMID- 17747785 TI - Argon Content of the Martian Atmosphere at the Viking 1 Landing Site: Analysis by X-ray Fluorescence Spectroscopy. AB - The argon content of the martian atmosphere at the Viking 1 landing site is 90 degrees C) cracking reactions at great depth yielding predominately straight carbon chains. PMID- 17747814 TI - Associative behavioral modification in hermissenda: cellular correlates. AB - Three days of training consisting of trials of light paired with rotation produces a long-term modification of photopositive behavior in Hermissenda crassicornis. The behavioral modification depends on the temporal association of light and rotation. For animals that received light paired with rotation, significant increases in the spontaneous activity of type B photoreceptors were correlated with changes in photopositive behavior after training. A persistent tonic depolarization of type B photoreceptors can explain the cellular changes correlated with the long-term behavioral modification produced by the temporal association of light and rotation. PMID- 17747815 TI - Chemical Feeding Deterrent Mobilized in Response to Insect Herbivory and Counteradaptation by Epilachna tredecimnotata. AB - Experimentally damaged leaves of Cucurbita moschata mobilize substances to the damaged region within 40 minutes. These substances stimulate feeding by Acalymma vittata (Coleoptera: Chrysomelidae) and inhibit feeding by Epilacha tredecimnotata (Coleoptera: Coccinelidae). Under natural conditions, Epilachna cuts a circular trench in the leaf before feeding on the encircled leaf material, thus preventing mobilization of the deterrent substances to the feeding area. PMID- 17747816 TI - Pit connections and translocation in red algae. PMID- 17747818 TI - PRODUCTS and MATERIALS. PMID- 17747817 TI - Pit connections and translocation in red algae. PMID- 17747819 TI - THE REHABILITATION OF THE AMERICAN COLLEGE, AND THE PLACE OF CHEMISTRY IN IT. PMID- 17747820 TI - COLLEGE CHEMISTRY BEYOND THE ELEMENTARY COURSE. PMID- 17747821 TI - HOW CAN THE BUREAU OF EDUCATION HELP THE CITY SUPERINTENDENT OF SCHOOLS? PMID- 17747822 TI - WATER VAPOR IN THE ATMOSPHERE OF THE PLANET MARS. PMID- 17747823 TI - PROGRESS OF THE INTERNATIONAL LANGUAGE ESPERANTO. PMID- 17747824 TI - GEOLOGY AND COSMOGONY. PMID- 17747825 TI - "UM" AND "IUM" ENDINGS. PMID- 17747827 TI - THE CONSERVATION OF MASS AND THE PASSING OF MATTER. PMID- 17747826 TI - BOTANICAL NOTES. PMID- 17747828 TI - Animal welfare. PMID- 17747829 TI - Columbia river gorge. PMID- 17747830 TI - Photon counting. PMID- 17747831 TI - U.S. Pullout from IIASA. PMID- 17747833 TI - Aspartame in canadian soft drinks. PMID- 17747832 TI - Aspartame in canadian soft drinks. PMID- 17747834 TI - Animal welfare. PMID- 17747835 TI - The revolution in computers and electronics. PMID- 17747836 TI - Electronics and computers. PMID- 17747837 TI - Computers: a survey of trends and limitations. AB - Enormous progress in electronic technology is accelerating the use of computers in everyday life. In this article trends in hardware, input-output technology, computer architecture, software, communications, and artificial intelligence are examined and complexity is identified as a limitation to further progress. Promising directions of research, which may extend the range of computer applications, are discussed. PMID- 17747838 TI - Some recent advances in computer graphics. PMID- 17747839 TI - Software. AB - Two principal themes are observed in software development, both aimed at improving the productivity of developing and maintaining new applications. The first is to provide increasingly rich system programming function in order to handle the details of managing hardware resources. The second is to provide application development facilities with logical structures and building blocks more closely aligned with the logic of the application itself. An additional challenge is to provide these in a way that will allow continued enhancement of existing software. PMID- 17747840 TI - The UNIX Operating System: A Model for Software Design. AB - The UNIX operating system, a general-purpose time-sharng system, has, without marketing, advertising, or technical support, become widely used by universities and scientific research establishments. It is the de facto standard of comparison for such systems and has spawned a small industry of suppliers of UNIX variants and look-alikes. This article attempts to uncover the reasons for its success and to draw some lessons for the future of operating systems. PMID- 17747841 TI - Computers in scientific instrumentation. PMID- 17747842 TI - Ultrafast phenomena in semiconductor devices. AB - Evolving high-speed semiconductor technology requires a more complete understanding of semiconductors on a picosecond time scale. This article discusses ultrafast phenomena that may influence device performance and describes new experimental methods utilizing short optical pulses to investigate materials and device structures. PMID- 17747843 TI - University role in the computer age. AB - Realization of the potential of computer electronics for enhanced human productivity and economic impact depends strongly on the university. New manpower and continuing education for the existing work force as well as new ideas for research and development will come from that sector. University-industry coupling offers mutual advantages to the partners and benefits to the nation in the computer age. PMID- 17747844 TI - Advances in process control. AB - Advances in electronics and computers have enabled industries to attain better control of their processes with resulting increases in quality, productivity, profitability, and compliance with government regulations. With a hierarchy of computers, distributed data acquisition, and information processing and control, it is possible to achieve overall optimum performance of a plant. While further advances in microprocessors and large-scale integration will be useful to the process engineer, major improvements in process control await advances in sensor technology and software. PMID- 17747845 TI - Computers in manufacturing. AB - Computers are now widely used in product design and in automation of selected areas in factories. Within the next decade, the use of computers in the entire spectrum of manufacturing applications, from computer-aided design to computer aided manufacturing and robotics, is expected to be practical and economically justified. Such widespread use of computers on the factory floor awaits further advances in computer capabilities, the emergence of systems that are adaptive to the workplace, and the development of interfaces to link islands of automation and to allow effective user communications. PMID- 17747846 TI - Japan--u.s. Competition: semiconductors are the key. AB - Japan appears to have achieved a breakthrough with its success in selling the 16K random access memory chip. The rivalry between Japan and the United States over integrated circuits could make the 1980's crucial years in the contest for the lead in the world electronics trade. PMID- 17747847 TI - Evolution of the intelligent telecommunications network. PMID- 17747848 TI - Business use of satellite communications. AB - The development of satellite communications over the past two decades has been very rapid. At the same time, space and electronics technologies have progressed sufficiently to allow satellite systems to keep pace with user requirements and to expand in several dimensions, including capacity, coverage, performance, reliability, and variety of services. The principal services provided by satellite systems have been long-distance trunks for telephone circuits and television program distribution. Recently, data transmission and network services have been added to meet emerging requirements for "office of the future" and other business applications. Data services are now expected to be the most rapidly expanding element of satellite communications. PMID- 17747849 TI - Computer networks: prospects for scientists. AB - Computer networks are an integral part of the rapid expansion of computing. Their emergence depends both on evolving communication technologies, such as packet switching and satellites, and on diverse experiments and innovations in the software tools that exploit communications. The tools provide computer users with facilities such as electronic mail, access to remote computers, and electronic bulletin boards. Scientists can both adapt and extend tools to meet the communication needs of their work, and several networks are developing to serve particular scientific communities. PMID- 17747850 TI - Computers and electronics for individual services. AB - Personal computers priced for the consumer market have a wide range of applications and variable memory, computational, and display capabilities. The genesis of individual computing devices, some of their applications, and the market for personal computers are discussed in this article. PMID- 17747852 TI - Captions for divider pages, computers and electronics. PMID- 17747851 TI - Database systems. AB - Database systems, computer systems that are principally devoted to the management of large amounts of data, are becoming more and more important to the operation of many enterprises. This article surveys the technology of database software and hardware, describing some of the principal issues related to the user's view of data, sharing, concurrent access, security, and integrity. PMID- 17747854 TI - "Prevention of dishonesty in science". PMID- 17747853 TI - "Institutional response". PMID- 17747855 TI - Reactor mishap raises broad questions. PMID- 17747856 TI - Antinuclear movement gains momentum. PMID- 17747857 TI - Congressman Wants Millar, Head of NIOSH, to Move. PMID- 17747858 TI - Armageddon closer. PMID- 17747859 TI - Firm offers to finance a space shuttle. PMID- 17747860 TI - Tracing sources of Acid rain causes big stir. PMID- 17747861 TI - PRODUCTS and MATERIALS. PMID- 17747862 TI - This week in science. PMID- 17747863 TI - The human--voyager 2 collaboration. PMID- 17747864 TI - Erratum. AB - In Eliot Marshall's News & Comment article "Fallout from Pacific reaches Congress" (14 July, p. 123), Rongelap Atoll is described as "three-tenths of a square mile of sand and coconut palms." The atoll actually contains about 4 square miles of land surfaces. In addition, the lagoon encompassed by the atoll covers approximately 350 square miles. PMID- 17747865 TI - Caldera unrest. PMID- 17747867 TI - Smithsonian, Indian Leaders Call a Truce: An agreement will result in the reburial of part of the Smithsonian's collection of Native Indian remains. PMID- 17747866 TI - High-Energy Management Stirs Up Energy Research: In his drive to keep R&D programs at the Office of Energy Research productive, Robert O. Hunter, Jr., has shaken up scientists and angered many legislators. PMID- 17747868 TI - White house, congress push computer plan. PMID- 17747869 TI - In Search of the Plastic Potato: Scientists in the emerging field of biopolymer engineering are aiming to produce bacteria and, eventually, food crops that are genetically tailored to yield a whole new breed of plastics. PMID- 17747870 TI - Redesigning Nature's Plastics Factories. PMID- 17747871 TI - Algebra: a hotbed of radicalism. PMID- 17747872 TI - Say It Again in Plain Algebra: The growing use of computer algebra systems has driven mathematicians to find ways of simplifying the horrendously complex expressions number crunchers sometimes spit out. PMID- 17747873 TI - Computer-age stargazing. PMID- 17747874 TI - Cocaine trends. PMID- 17747875 TI - The selling of cold fusion. PMID- 17747876 TI - Amateur hours on hubble telescope. PMID- 17747877 TI - Saving madagascar wildlife. PMID- 17747878 TI - Gupta's Defense. PMID- 17747879 TI - Wistar cleared by Argentina. PMID- 17747880 TI - History of meteorites from the moon collected in antarctica. AB - In large asteroidal or cometary impacts on the moon, lunar surface material can be ejected with escape velocities. A few of these rocks were captured by Earth and were recently collected on the Antarctic ice. The records of noble gas isotopes and of cosmic ray-produced radionuclides in five of these meteorites reveal that they originated from at least two different impact craters on the moon. The chemical composition indicates that the impact sites were probably far from the Apollo and Luna landing sites. The duration of the moon-Earth transfer for three meteorites, which belong to the same fall event on Earth, lasted 5 to 11 million years, in contrast to a duration of less than 300,000 years for the two other meteorites. From the activities of cosmic ray-produced radionuclides, the date of fall onto the Antarctic ice sheet is calculated as 70,000 to 170,000 years ago. PMID- 17747881 TI - Experiments with high-energy neutrino beams. AB - Experiments in which high-energy neutrinos were used as projectiles have made substantial contributions to our understanding of both weak and strong interactions, as well as the structure of hadrons. This article offers some illustrations. It recalls the discovery of the neutral weak current and some experiments on its nature. The sections on charged-current inclusive scattering recall the important role of these experiments in the understanding of the quark structure of the nucleon and the validity of quantum chromodynamics. The section on dimuon production illustrates the role of neutrino experiments in establishing the Glashow-Iliopoulos-Maiani current as well as the measurement of the structure function of the strange quark in the nucleon. PMID- 17747882 TI - High-resolution microwave images of saturn. AB - An analysis of high-resolution microwave images of Saturn and Saturn's individual rings is presented. Radio interferometric observations of Saturn taken at the Very Large Array in New Mexico at wavelengths of 2 and 6 centimeters reveal interesting new features in both the atmosphere and rings. The resulting maps show an increase in brightness temperature of about 3 K from equator to pole at both wavelengths, while the 6-centimeter map shows a bright band at northern mid latitudes. The data are consistent with a radiative transfer model of the atmosphere that constrains the well-mixed, fully saturated, NH(3) mixing ratio to be 1.2 x 10(-4) in a region just below the NH(3) clouds, while the observed bright band indicates a 25 percent relative decrease of NH(3) in northern mid latitudes. Brightness temperatures for the classical rings are presented. Ring brightness shows a variation with azimuth and is linearly polarized at an average value of about 5 percent. The variations in ring polarization suggest that at least 20 percent of the ring brightness is the result of a single scattering process. PMID- 17747883 TI - A near-optimum parallel planarization algorithm. AB - A near-optimum parallel planarization algorithm is presented. The planarization algorithm, which is designed to embed a graph on a plane, uses a large number of simple processing elements called neurons. The proposed system, composed of an N x N neural network array (where N is the number of vertices), not only generates a near-maximal planar subgraph from a nonplanar graph or a planar graph but also embeds the subgraph on a single plane within 0(1) time. The algorithm can be used in multiple-layer problems such as designing printed circuit boards and routing very-large-scale integration circuits. PMID- 17747884 TI - Shear forces in molecularly thin films. AB - Monte Carlo and molecular dynamics methods have been used to study the shearing behavior of an atomic fluid between two plane-parallel solid surfaces having the face-centered cubic (100) structure. A distorted, face-centered cubic solid can form epitaxially between surfaces that are separated by distances of one to five atomic diameters. Under these conditions a critical stress must be overcome to initiate sliding of the surfaces over one another at fixed separation, temperature, and chemical potential. As sliding begins, a layer of solid exits the space between the surfaces and the remaining layers become fluid. PMID- 17747885 TI - Aerosols, cloud microphysics, and fractional cloudiness. AB - Increases in aerosol concentrations over the oceans may increase the amount of low-level cloudiness through a reduction in drizzle-a process that regulates the liquid-water content and the energetics of shallow marine clouds. The resulting increase in the global albedo would be in addition to the increase due to enhancement in reflectivity associated with a decrease in droplet size and would contribute to a cooling of the earth's surface. PMID- 17747886 TI - Evidence for a heterogeneous upper mantle in the cabo ortegal complex, Spain. AB - A well-preserved fragment of a heterogeneous upper mantle is present in the Cabo Ortegal Complex (Spain). This section is made of harzburgite containing a large volume of pyroxenite. The pyroxenite is concentrated in a layer 300 meters thick by 3 kilometers long. In this layer, ultramafic rocks, essentially pyroxenite (massive websterite and clinopyroxenite) and minor dunite, alternate without any rhythmicity. Part of this layering is of primary magmatic origin and possibly resulted from crystallization of magmas in dikes intruded into the host peridotite under mantle conditions. PMID- 17747887 TI - Foregut fermentation in the hoatzin, a neotropical leaf-eating bird. AB - The only known case of an avian digestive system with active foregut fermentation is reported for the hoatzin (Opisthocomus hoazin), one of the world's few obligate folivorous (leaf-eating) birds. Hoatzins are one of the smallest endotherms with this form of digestion. Foregut fermentation in a flying bird may be explained by increased digestive efficiency by selection of highly fermentable and extremely patchy resources, coupled with microbial nutritional products and secondary compound detoxification. This unexpected digestive system gives a new perspective to the understanding of size limitations of vertebrate herbivores and to the evolution of foregut fermentation. PMID- 17747889 TI - A reasonable outcome: the politics of earthquake prediction. PMID- 17747888 TI - Views from chicago: memoirs of an unregulated economist. PMID- 17747890 TI - Geologic collisions: impact cratering. PMID- 17747892 TI - Products & materials. PMID- 17747891 TI - Interactions at sea: seabirds and other marine vertebrates. PMID- 17747893 TI - This week in science. PMID- 17747894 TI - On being a scientist. PMID- 17747895 TI - SSC Test Magnets. PMID- 17747896 TI - Asian-american students. PMID- 17747897 TI - Response:SSC Test Magnets. PMID- 17747898 TI - NSF Education Head Makes Risky Bid: Bassam Shakhashiri has been making an unusual public push for a big budget increase, but he is up against the deficit and resentment within the foundation. PMID- 17747899 TI - Getting energy into the schools. PMID- 17747900 TI - Research Chief to Leave DOE. PMID- 17747901 TI - Zero resistance at 250 k? PMID- 17747902 TI - IBM Wins a Patent for Thallium Superconductor: But the materials were discovered by Allen Hermann of the University of Arkansas, whose own patent claim is still pending. PMID- 17747903 TI - Landsat: cliff-hanging, again. PMID- 17747904 TI - Bromley targets superconductors. PMID- 17747905 TI - B-2 comes up short. PMID- 17747907 TI - Ozone hits bottom again. PMID- 17747906 TI - New Physics, Old Rivalries: Geneva was set to be the center of world attention for exciting new findings in high energy physics--but their competitiors in California had other ideas. PMID- 17747908 TI - Basic Measurements Lead to Physics Nobel: Their work on atomic properties led to atomic clocks, magnetic resonance imaging, and verifications of quantum mechanics. PMID- 17747910 TI - Building on noble research. PMID- 17747911 TI - Would It Be Mars Without NASA? PMID- 17747909 TI - Early work rewarded. PMID- 17747912 TI - Peace corps to help environment. PMID- 17747913 TI - Tech transfer triggers protest. PMID- 17747914 TI - Russian bugs drafted in u.s. War. PMID- 17747915 TI - Van allen wins space nobel. PMID- 17747916 TI - Burgess shale faunas and the cambrian explosion. AB - Soft-bodied marine faunas from the Lower and Middle Cambrian, exemplified by the Burgess Shale of British Columbia, are a key component in understanding the major adaptive radiations at the beginning of the Phanerozoic ("Cambrian explosion"). These faunas have a widespread distribution, and many taxa have pronounced longevity. Among the components appear to be survivors of the preceding Ediacaran assemblages and a suite of bizarre forms that give unexpected insights into morphological diversification. Microevolutionary processes, however, seem adequate to account for this radiation, and the macroevolutionary patterns that set the seal on Phanerozoic life are contingent on random extinctions. They weeded out the morphological spectrum and permitted rediversification among surviving clades. Although the predictability of which clades will play in successive acts of the Phanerozoic theater is low, at least the outlines of the underlying ecological plot are already clear from the opening of the drama. PMID- 17747917 TI - The chemistry of solid-state electronics. AB - Since the original theoretical insights of Bardeen and Shockley about 40 years ago, the progress of solid-state electronics has been paced by the ability to control chemical bonding structures, particularly at surfaces and interfaces. The functioning of solid-state devices depends on being able to produce interfacial structures with a minimum number of defective chemical bonds. A series of chemical discoveries and insights, on germanium (Ge) and silicon (Si) surfaces and gallium arsenide-aluminum arsenide (GaAs-AlAs) interfaces, has brought the electronics revolution to its present state of development. In most cases, the technological consequences of these accidental discoveries could not be accurately foreseen. With that caution, the technological prognosis for some current research is also reviewed. PMID- 17747918 TI - Inclusion systems of organic molecules in restacked single-layer molybdenum disulfide. AB - Novel materials have been obtained by restacking single-layer molybdenum disulfide (MoS(2)) with organic molecules included between the layers. A large variety of organic molecules can be included between layers of MoS(2) and other transition-metal dichalcogenides. The films with the included organics are formed at the interface between an aqueous suspension of the MoS(2) and a water immiscible organic liquid. The organic molecules are not necessarily electron donors. A highly oriented, conducting film of restacked MoS(2) containing ferrocene is presented as an example. PMID- 17747919 TI - Toward protein tertiary structure recognition by means of associative memory hamiltonians. AB - The statistical mechanics of associative memories and spin glasses suggests ways to design Hamiltonians for protein folding. An associative memory Hamiltonian based on hydrophobicity patterns is shown to have a large capacity for recall and to be capable of recognizing tertiary structure for moderately variant sequences. PMID- 17747920 TI - Styles of volcanism on venus: new arecibo high resolution radar data. AB - Arecibo high-resolution (1.5 to 2 km) radar data of Venus for the area extending from Beta Regio to western Eisila Regio provide strong evidence that the mountains in Beta and Eisila Regiones and plains in and adjacent to Guinevere Planitia are of volcanic origin. Recognized styles of volcanism include large volcanic edifices on the Beta and Eisila rises related to regional structural trends, plains with multiple source vents and a mottled appearance due to the ponding of volcanic flows, and plains with bright features surrounded by extensive quasi-circular radar-dark halos. The high density of volcanic vents in the plains suggests that heat loss by abundant and widely distributed plains volcanism may be more significant than previously recognized. The low density of impact craters greater than 15 km in diameter in this region compared to the average density for the higher northern latitudes suggests that the plains have a younger age. PMID- 17747921 TI - Peptide biology: regulatory peptides. PMID- 17747923 TI - Oceangoing mollusks: pelagic snails. PMID- 17747922 TI - Mulliken: robert s. Mulliken: life of a scientist. PMID- 17747924 TI - Uncertainties about Mammals: Evolution of Life Histories of Mammals. PMID- 17747925 TI - Products & materials. PMID- 17747926 TI - THE GENERAL BIOLOGY COURSE AND THE TEACHING OF ELEMENTARY BOTANY AND ZOOLOGY IN AMERICAN COLLEGES AND UNIVERSITIES. PMID- 17747927 TI - STATE ACADEMIES OF SCIENCE. PMID- 17747928 TI - RESULTS OF THE TOTAL SOLAR ECLIPSE OF MAY 29 AND THE RELATIVITY THEORY. PMID- 17747929 TI - AN APPEAL. PMID- 17747930 TI - STEINDACHNERIDION. PMID- 17747932 TI - THE HARVEIAN FESTIVAL OF THE ROYAL COLLEGE OF PHYSICIANS OF LONDON. PMID- 17747931 TI - SOMATIC VARIATION. PMID- 17747933 TI - ACOUSTIC EFFECTS OF WIRES. PMID- 17747935 TI - Paleoglaciology. PMID- 17747934 TI - GERMINATING FRESHLY HARVESTED WINTER WHEAT. PMID- 17747936 TI - Marine biology on palau. PMID- 17747937 TI - Explaining meteorites. PMID- 17747938 TI - Explaining meteorites. PMID- 17747939 TI - Nickel for your thoughts: urey and the origin of the moon. AB - The theories of Harold C. Urey (1893-1981) on the origin of the moon are discussed in relation to earlier ideas, especially George Howard Darwin's fission hypothesis. Urey's espousal of the idea that the moon had been captured by the earth and has preserved information about the earliest history of the solar system led him to advocate a manned lunar landing. Results from the Apollo missions, in particular the deficiency of siderophile elements in the lunar crust, led him to abandon the capture selenogony and tentatively adopt the fission hypothesis. PMID- 17747940 TI - The Organization of Work in China's Communes. AB - There has been speculation that China's communes are undergoing drastic changes and that work patterns are being redefined so as to make individuals or households the basic production units in agriculture. A brief but intensive anthropological study in 17 communes suggests that, although collectivization is still considered to be the ideal form in more advanced areas, responsibility for some tasks is being assigned to households in some poorer communes in an effort to increase production and farm incomes and enhance development. Significant permanent improvements seem hinged to the rise of rural industry, which increasingly rewards individual efforts within the context of a basically collective social organization. The system is complex and is more flexible than it has been in the recent past. PMID- 17747941 TI - Solutions to Environmental and Economic Problems (STEEP). AB - This article describes one model for organizing and mobilizing scientific resources to address the highly complex and costly problem of soil erosion in the Pacific Northwest. With a U.S. Department of Agriculture grant to the agricultural experiment stations in Washington, Oregon, and Idaho, as well as supplementary state and federal funds, STEEP awards intermediate-term (15 year) grants for research in five areas: tillage and plant management, plant design, erosion and runoff predictions, pest management, and socioeconomics of erosion control. Most of the research projects require collaboration across disciplines and, in some instances, across state boundaries. After 6 years of effort the results obtained with STEEP indicate that the model might be applicable to other regions and problems. PMID- 17747942 TI - Evading the soviet ear at glen cove. PMID- 17747943 TI - U.N. Space conference ends in compromise. PMID- 17747944 TI - NASA Floats a Global Plan. PMID- 17747945 TI - Sun, weather, and climate: a connection? PMID- 17747946 TI - Computer graphics comes to statistics. PMID- 17747947 TI - Pulsed neutron sources okayed. PMID- 17747948 TI - Relics of solar system history. PMID- 17747949 TI - A technological controversy. PMID- 17747950 TI - Neurobiology. PMID- 17747951 TI - Biological rhythmicity. PMID- 17747952 TI - Western deer: a status report. PMID- 17747953 TI - Recognition of a hidden mineral deposit by an artificial intelligence program. AB - A computer program that uses artificial intelligence techniques has successfully identified the location of a porphyry molybdenum deposit. Given geological maps of readily available predrilling exploration data for Mount Tolman in Washington State and using rules obtained from a porphyry molybdenum exploration specialist, the program (called PROSPECTOR) identified the location of previously unknown ore grade mineralization. This appears to be the first reported determination of the location of mineralization by such a computer-based approach. PMID- 17747954 TI - Carbonate dissolution and sedimentation on the mid-atlantic continental margin. AB - The calcium carbonate content was determined for core tops from two transects on the upper slope to lower rise on the mid-Atlantic continental margin. Carbonate content in the sediment increases from approximately 5 percent (by weight) on the upper slope to more than 30 percent on the upper rise. A zone of low-carbonate content extends from 3000 to 4400 meters. Below 4400 meters, the percent carbonate increases. An examination of dissolution indices in these core tops indicates that the low-carbonate zone is associated with intense dissolution. Below 4400 meters, dissolution decreases and carbonate is well preserved. The decrease in dissolution occurs where the high-velocity core of the Western Boundary Undercurrent is first encountered. PMID- 17747955 TI - Functional Morphology of Homo habilis. AB - Olduvai hominid (O.H.) fossils 7, 8, and 35 represent the earliest species of the genus Homo dated at 1.76 million years. The O.H. 7 hand, jaw, and skull and the O.H. 8 foot come from one subadult individual, and the O.H. 35 leg are also those of Homo habilis. The skeleton represents a mosaic of primitive and derived features, indicating an early hominid which walked bipedally and could fabricate stone tools but also retained the generalized hominoid capacity to climb trees. PMID- 17747956 TI - Endomycorrhizal role for interspecific transfer of phosphorus in a community of annual plants. AB - Phosphorus-32 applied to leaves of Plantago erecta in a serpentine annual grassland reached the shoots of about 20 percent of the close neighbors. Vesicular-arbuscular mycorrhizae connect the root systems of neighbors of different species and probably mediate nutrient transfers among them. Spatial patterns of transfer show that taxonomic affinity, distance from donor, and size of recipient do not serve as predictors of transfer and that models of transfer by simple diffusion are not appropriate. No alternative predictor was discovered. The results underscore the importance of belowground interactions in explaining neighbor effects, but the factors controlling nutrient transfer and its consequences for community structure appear complex. PMID- 17747957 TI - Calcium ionophore a23187 stimulates cytokinin-like mitosis in funaria. AB - The plant hormone cytokinin stimulates asymmetrical division in target cells of the protonema of the moss Funaria hygrometrica, leading to bud formation. The initial division can be induced in the absence of cytokinin by the calcium ionophore A23187 in medium containing calcium. These findings suggest that increases in the concentration of intracellular calcium are essential to bud initiation. Therefore mitotic regulation by cytokinin may be due, at least in part, to the modulation of intracellular calcium ion concentration. PMID- 17747958 TI - COSMICAL PHYSICS. PMID- 17747960 TI - SANITATION IN VERA CRUZ. PMID- 17747959 TI - BOTANY IN THE AGRICULTURAL COLLEGE. PMID- 17747961 TI - BOTANISTS OF THE CENTRAL STATES. PMID- 17747962 TI - FOREIGN STUDENTS AND THE UNITED STATES. PMID- 17747963 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17747965 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17747964 TI - A RECENT CASE OF MUSHROOM INTOXICATION. PMID- 17747966 TI - THE WORK OF THE U. S. FISHERIES MARINE BIOLOGICAL STATION AT BEAUFORT, N. C., DURING 1913. PMID- 17747967 TI - THE TRANSMISSION OF TERRESTRIAL RADIATION BY THE EARTH'S ATMOSPHERE IN SUMMER AND IN WINTER. PMID- 17747968 TI - THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE STANDARDS OF VENTILATION IN THE LIGHT OF RECENT RESEARCH. PMID- 17747969 TI - SOME ENGINEERING PROBLEMS IN VENTILATION. PMID- 17747970 TI - THE PACIFIC ASSOCIATION OF SCIENTIFIC SOCIETIES. PMID- 17747971 TI - CONDITIONS AT THE UNIVERSITY OF UTAH. PMID- 17747973 TI - MINUTES OF THE COUNCIL. PMID- 17747972 TI - THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17747974 TI - THE PRESENTATION OF THE FUNDAMENTAL CONCEPTIONS OF MECHANICS. PMID- 17747975 TI - GET THE UNITS RIGHT. PMID- 17747976 TI - A SPURIOUS CASE OF MULTIPLE HUMAN BIRTHS. PMID- 17747977 TI - THE BIOLOGICAL SOCIETY OF WASHINGTION. PMID- 17747979 TI - ON THE GENUS TRACHODON. PMID- 17747978 TI - ON THE OSMOTIC PRESSURE OF THE JUICES OF DESERT PLANTS. PMID- 17747980 TI - THE SOCIETY OF AMERICAN BACTERIOLOGISTS. II. PMID- 17747981 TI - TRUTH AND ERROR. PMID- 17747982 TI - TRUTH AND ERROR. PMID- 17747983 TI - INCONSIDERATE LEGISLATION ON BIRDS. PMID- 17747984 TI - ELEVENTH ANNUAL MEETING OF THE GEOLOGICAL SOCIEIY OF AMERICA, DECEMBER 28TH, 29TH AND 30TH, NEW YORK. II. PMID- 17747985 TI - WINTER MEETING OF THE ANTHROPOLOGICAL SECTION OF THE AMERICAN ASSOCIATION. PMID- 17747986 TI - ZOOLOGICAL BIBLIOGRAPHY. PMID- 17747987 TI - MATTER, ENERGY, FORCE AND WORK. PMID- 17747988 TI - NOTES ON INORGANIC CHEMISTRY. PMID- 17747989 TI - COLLECTIONS OF THE PROVINCIAL MUSEUM OF VICTORIA, BRITISH COLUMBA. PMID- 17747990 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17747991 TI - ZOOLOGICAL NOTES. PMID- 17747992 TI - Federa1 Support of University Research. PMID- 17747993 TI - The Chemist's Most Creative Years: The 2500 ablest of the world's chemists attained their maximum production rate at ages 30 through 34. PMID- 17747995 TI - News of Science. PMID- 17747994 TI - Irving Langmuir, Man of Many Interests. PMID- 17747996 TI - Visual Thresholds for Detecting an Earth Satellite. PMID- 17747998 TI - Formula for Inferring Atmospheric Density from the Motion of Artificial Earth Satellites. PMID- 17747997 TI - Effect of Length of Observing Time on the Visual Threshold for Detecting a Faint Satellite. PMID- 17748000 TI - Blood-Group Nomenclature. PMID- 17748001 TI - Blood-Group Nomenclature. PMID- 17748002 TI - Legibility. PMID- 17748003 TI - Editor's note. PMID- 17748004 TI - Environmental quality. PMID- 17748005 TI - Teletext systems. PMID- 17748006 TI - Teletext systems. PMID- 17748007 TI - Sex and mathematics. PMID- 17748008 TI - Quaternary climates and sea levels of the u.s. Atlantic coastal plain. AB - Uranium-series dating of corals from marine deposits of the U.S. Atlantic Coastal Plain coupled with paleoclimatic reconstructions based on ostracode (marine) and pollen (continent) data document at least five relatively warm intervals during the last 500,000 years. On the basis of multiple paleoenvironmental criteria, we determined relative sea level positions during the warm intervals, relative to present mean sea level, were 7 +/- 5 meters at 188,000 years ago, 7.5 +/- 1.5 meters at 120,000 years ago, 6.5 +/- 3.5 meters at 94,000 years ago, and 7 +/- 3 meters at 72,000 years ago. The composite sea level chronology for the Atlantic Coastal Plain is inconsistent with independent estimates of eustatic sea level positions during interglacial intervals of the last 200,000 years. Hydroisostatic adjustment from glacial-interglacial sea level fluctuations, lithospheric flexure, and isostatic uplift from sediment unloading due to erosion provide possible mechanisms to account for the discrepancies. Alternatively, current eustatic sea level estimates for the middle and late Quaternary may require revision. PMID- 17748009 TI - Telecommunications in alaskan villages. AB - A recently installed satellite system now provides modern long-distance telecommunication services to 100 rural Alaskan villages, most of whose residents are Alaska Natives. In most villages no local telephone or television distribution facilities have yet been installed. Local telephone exchange service appears to be economically marginal unless modest regulatory changes are made. Television delivery presents more difficult problems involving technical and organizational structure. If, after weighing the potential social and cultural effects, village residents elect to acquire television, a delivery system based on low-power transmitters in the villages, local government as the basic organizational and economic unit, and a statewide nonprofit service organization, is the feasible system best suited to village needs. PMID- 17748011 TI - Will u.s. Skip neutron scattering derby? PMID- 17748010 TI - Science and technology in the white house, 1977 to 1980: part 2. AB - This is the second half of a two-part article on Administration science and technology policy during the period 1977 to 1980. The first part discussed the role of the Office of Science and Technology Policy (OSTP) in the context of the overall federal policy-making framework and institutional structure and described specific activities aimed at strengthening U.S. science and technology, fostering industrial innovation, enhancing relationships among government, universities, and industry, and improving the regulatory process. This part focuses on OSTP activities related to national security and foreign policy, space, energy and the environment, health, and agriculture, and discusses OSTP advisory mechanisms and planning efforts. PMID- 17748012 TI - Too much congressional direction? PMID- 17748013 TI - Revlon funds animal test research. PMID- 17748014 TI - Most additives are harmless. PMID- 17748015 TI - Pope john paul meets the scientists. PMID- 17748017 TI - Why does sickle trait persist? PMID- 17748016 TI - Genentech: is its glamor gone? PMID- 17748018 TI - Who will build the next supercomputer? PMID- 17748019 TI - Darwin novelized. PMID- 17748020 TI - Hales's Activities. PMID- 17748021 TI - Achievements in astronomy. PMID- 17748022 TI - Solid state physics. PMID- 17748023 TI - Biogeochemistry. PMID- 17748024 TI - Simulated wind pollination and airflow around ovules of some early seed plants. AB - Scale models of various early seed plant ovules and cupules were analyzed both for their characteristic air disturbance patterns and for the frequency of impact with airborne models of pollen (pseudopollen). The fossils on which the models were based had been arranged in an evolutionary sequence purporting to show the origin of the integument by the acropetal fusion and reduction in length of a subtending truss of lobes. Wind tunnel analyses of scale models showing the various stages in the consolidation of these preintegumentary lobes indicated that turbulent flow increases and becomes localized around the nucellar apex (salpinx) with the syngenesis and length reduction of those lobes. Similarly, the frequency of windborne pseudopollen impact increased. Thus, the transition from the megasporangium to the fully integumented ovule appears to favor increased wind-mediated pollination. PMID- 17748025 TI - Diatoms as hydrographic tracers: example from bering sea sediments. AB - Variations in the distribution of diatom species in surface sediments mirror distinct hydrographic regimes on the Bering shelf. Spring salinity fronts divide the water column into four zones with different vertical structures and different productivity patterns. Four assemblages of diatoms can be distinguished in sediments underlying the zones. PMID- 17748026 TI - A three-band hand-held radiometer for field use. AB - A self-contained, hand-held radiometer designed for field use has been constructed and tested. The 4.5-kilogram device, consisting of a strap-supported electronics module and a hand-held probe containing three sensors, is powered by flashlight and transistor radio batteries, uses two silicon and one lead sulfide detector, has three liquid-crystal displays, features sample-and-hold radiometric sampling, and is spectrally configured to Landsat-D's thematic mapper bands TM3 (0.63 to 0.69 micrometer), TM4 (0.76 to 0.90 micrometer), and TM5 (1.55 to 1.75 micrometers). The device was designed to collect ground-truth data for the thematic mapper and to facilitate ground-based, remote-sensing studies of natural materials in situ. Prototype instruments were extensively tested under laboratory and field conditions, with satisfactory results. PMID- 17748027 TI - Decipherment of the earliest tablets. AB - The first signs of writing were crudely impressed on clay tablets. These signs are found to represent and stand for clay tokens used for recording prior to writing. The recent decoding of a series of tokens makes it possible to identify the signs as units of grain metrology, land measure, animal numeration, and other economic units. PMID- 17748029 TI - Minor planet satellites. PMID- 17748028 TI - Atmospheric trace gases in antarctica. AB - Trace gases have been measured, by electron-capture gas chromatography and gas chromatography-mass spectrometry techniques, at the South Pole (SP) in Antarctica and in the U.S. Pacific Northwest (PNW) ( approximately 45 degrees N) during January of each year from 1975 to 1980. These measurements show that the concentrations of CCl(3)F, CCl(2)F(2), and CH(3)CCl(3) have increased exponentially at substantial rates. The concentration of CCl(3)F increased at 12 percent per year at the SP and at 8 percent per year in the PNW; CCl(2)F(2) increased at about 9 percent per year at both locations, and CH(3)CCl(3) increased at 17 percent per year at the SP and 11.6 percent per year at the PNW site. There is some evidence that CCl(4) ( approximately 3 percent per year) and N(2)O (0.1 to 0.5 percent per year) may also have increased. Concentrations of nine other trace gases of importance in atmospheric chemistry are also being measured at these two locations. Results of the measurements of CHClF(2)(F-22), C(2)Cl(3)F(3)(F-113), SF(6), C(2)-hydrocarbons, and CH(3)Cl are reported here. PMID- 17748030 TI - Geothermal System at 21{degrees}N. PMID- 17748032 TI - The One World of Stars. PMID- 17748031 TI - Address of the President of the United States. PMID- 17748033 TI - The Quantitative Theory of Autoradiography Illustrated Through Experiments With P32 in the Chick Embryo. PMID- 17748034 TI - Crystalline Serotonin. PMID- 17748036 TI - The Homing Tendency of Shad. PMID- 17748035 TI - The Action of Ryanodine on the Contractile Process in Striated Muscle. PMID- 17748037 TI - Effect of Antiserum and Prolonged Cultivation on the Agglutinative Characteristics of a Type I Meningococcus. PMID- 17748038 TI - The Inactivation of Invertase by Tyrosinase. PMID- 17748039 TI - Mammary Carcinoma in Female Rats Fed 2-Acetylaminofluorene. PMID- 17748040 TI - A Simple Micro-Beaker for Use With the Beckman pH Meter (Model G). PMID- 17748041 TI - A Rapid Method for Preparing DDT in the Laboratory. PMID- 17748043 TI - THE SOUTHAMPTON MEETING OF THE BRITISH ASSOCIATION. PMID- 17748042 TI - Radiocardiography: A New Method for Studying the Blood Flow Through the Chambers of the Heart in Human Beings. PMID- 17748044 TI - THE TRANSMUTATION OF LEAD. PMID- 17748045 TI - STUDIES OF ATOMIC NUCLEI. PMID- 17748046 TI - MACKENZIE PARK AS A FIELD FOR SURVEY, EXPLORATION, LITERATURE AND ART. PMID- 17748047 TI - THE UNSATISFACTORY STATUS OF THE GLACIAL CONTROVERSY. PMID- 17748048 TI - WILLIAM ALBERT HAMILTON. PMID- 17748049 TI - DR. W. D. RILEY ON EVOLUTION. PMID- 17748051 TI - THE SCIENCE LEAGUE OF AMERICA. PMID- 17748050 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17748052 TI - PROFESSOR ROBINSON'S TRIBUTE TO ASA GRAY. PMID- 17748053 TI - THE NAME N IN COS NT. PMID- 17748054 TI - THE PRODUCTION OF PURE ABSOLUTE ALCOHOL WITH CALCIUM CARBIDE AND ANHYDROUS COPPER SULPHATE. AB - (1) The above is recommended as an economical, convenient and quick method for producing absolute alcohol on a laboratory scale. If the distillation is executed with free flame, excessive or careless heating must be avoided near the end of the operation because of the copper acetylide in the residue. (2) Calcium carbide is recommended over potassium permanganate or anhydrous copper sulphate as a qualitative reagent in detecting traces of water in alcohol. PMID- 17748055 TI - MANOILOV'S REACTION FOR IDENTIFICATION OF THE SEXES. PMID- 17748056 TI - THE AMERICAN CHEMICAL SOCIETY. PMID- 17748058 TI - This week in science. PMID- 17748057 TI - HYDROGEN-MAGNESIUM HALIDES. PMID- 17748060 TI - Science: the best and worst of times. PMID- 17748059 TI - Ballooning around venus. PMID- 17748061 TI - Black holes--"ingestars"? PMID- 17748062 TI - The dot: alternative notation. PMID- 17748063 TI - Response: mexican seed bank. PMID- 17748064 TI - Mexican seed bank. PMID- 17748065 TI - Response: shakespeare and statistics. PMID- 17748066 TI - Shakespeare and statistics. PMID- 17748067 TI - DOE's Way-Out Reactors: The Department of Energy wants to spend $72 million next year to design and build reactors for military space applications; nothing like them has been built before. PMID- 17748068 TI - Shooting plutonium into space. PMID- 17748070 TI - Calgene breaks new ground. PMID- 17748069 TI - Engineering Crops to Resist Weed Killers: Plants that resist herbicides could, be a boon to chemical companies; a prototype may soon be field tested. PMID- 17748071 TI - Long-Range Forecasting: Truth or Consequences: Ability to anticipate El Nino conditions foreseen, but what if the forecasters should get it wrong? PMID- 17748072 TI - McLean-AMI Agree on Joint Venture: One of Harvard's principal psychiatric hospitals forms new company with American Medical International. PMID- 17748073 TI - VEGA's 1 and 2 Visit Halley: Soviet spacecraft obtain photos showing Halley is king of the comets. PMID- 17748074 TI - Weather balloons at venus. PMID- 17748076 TI - Delayed choice supports quantum theory. PMID- 17748075 TI - Testing Superposition in Quantum Mechanics: Several recent experiments explore the range of validity of the linear superposition principle in quantum mechanics; not yet answered is whether it applies to macroscopic objects. PMID- 17748077 TI - Cost of space-based laser ballistic missile defense. AB - Orbiting platforms carrying infrared lasers have been proposed as weapons forming the first tier of a ballistic missile defense system under the President's Strategic Defense Initiative. As each laser platform can destroy a limited number of missiles, one of several methods of countering such a system is to increase the number of offensive missiles. Hence it is important to know whether the cost exchange ratio, defined as the ratio of the cost to the defense of destroying a missile to the cost to the offense of deploying an additional missile, is greater or less than 1. Although the technology to be used in a ballistic missile defense system is still extremely uncertain, it is useful to examine methods for calculating the cost-exchange ratio. As an example, the cost of an orbiting infrared laser ballistic missile defense system employed against intercontinental ballistic missiles launched simultaneously from a small area is compared to the cost of additional offensive missiles. If one adopts lower limits to the costs for the defense and upper limits to the costs for the offense, the cost-exchange ratio comes out substantially greater than 1. If these estimates are confirmed, such a ballistic missile defense system would be unable to maintain its effectiveness at less cost than it would take to proliferate the ballistic missiles necessary to overcome it and would therefore not satisfy the President's requirements for an effective strategic defense. Although the method is illustrated by applying it to a space-based infrared laser system, it should be straightforward to apply it to other proposed systems. PMID- 17748078 TI - The 1985 nobel prize in economics. PMID- 17748079 TI - The VEGA Venus Balloon Experiment. AB - In June 1985, two instrumented balloons were placed in the atmosphere of Venus as part of the VEGA mission. Each balloon traveled about 30 percent of the way around the planet at a float altitude near 54 kilometers. In situ sensors measured pressure, temperature, vertical wind velocity, cloud particle backscatter, ambient light level, and frequency of lightning. A ground-based network of 20 radio antennas tracked the balloons by very long baseline interferometry (VLBI) techniques to monitor the Venus winds. The history, organization, and principal characteristics of this international balloon experiment are described. PMID- 17748080 TI - VEGA Balloon System and Instrumentation. AB - The VEGA Venus balloon radio transmissions received on Earth were used to measure the motion of the balloons and to obtain the data recorded by onboard sensors measuring atmospheric characteristics. Thus the balloons themselves, the gondolas, the onboard sensors, and the radio transmission system were all components of the experiment. A description of these elements is given, and a few details of data sampling and formatting are discussed. PMID- 17748081 TI - Overview of VEGA Venus Balloon in Situ Meteorological Measurements. AB - The VEGA balloons made in situ measurements of pressure, temperature, vertical wind velocity, ambient light, frequency of lightning, and cloud particle backscatter. Both balloons encountered highly variable atmospheric conditions, with periods of intense vertical winds occurring sporadically throughout their flights. Downward winds as large as 3.5 meters per second occasionally forced the balloons to descend as much as 2.5 kilometers below their equilibrium float altitudes. Large variations, in pressure, temperature, ambient light level, and cloud particle backscatter (VEGA-1 only) correlated well during these excursions, indicating that these properties were strong functions of altitude in those parts of the middle cloud layer sampled by the balloons. PMID- 17748082 TI - Determination of Venus Winds by Ground-Based Radio Tracking of the VEGA Balloons. AB - A global array of 20 radio observatories was used to measure the three dimensional position and velocity of the two meteorological balloons that were injected into the equatorial region of the Venus atmosphere near Venus midnight by the VEGA spacecraft on 11 and 15 June 1985. Initial analysis of only radial velocities indicates that each balloon was blown westward about 11,500 kilometers (8,000 kilometers on the night side) by zonal winds with a mean speed of about 70 meters per second. Excursions of the data from a model of constant zonal velocity were generally less than 3 meters per second; however, a much larger variation was evident near the end of the flight of the second balloon. Consistent systematic trends in the residuals for both balloons indicate the possibility of a solar-fixed atmospheric feature. Rapid variations in balloon velocity were often detected within a single transmission (330 seconds); however, they may represent not only atmospheric motions but also self-induced aerodynamic motions of the balloon. PMID- 17748083 TI - VEGA Balloon Dynamics and Vertical Winds in the Venus Middle Cloud Region. AB - The VEGA balloons provided a long-term record of vertical wind fluctuations in a planetary atmosphere other than Earth's. The vertical winds were calculated from the observed displacement of the balloon relative to its equilibrium float altitude. The winds were intermittent; a large burst lasted several hours, and the peak velocity was 3 meters per second. PMID- 17748084 TI - Thermal structure of the venus atmosphere in the middle cloud layer. AB - Thermal structure measurements obtained by the two VEGA balloons show the Venus middle cloud layer to be generally adiabatic. Temperatures measured by the two balloons at locations roughly symmetric about the equator differed by about 6.5 kelvins at a given pressure. The VEGA-2 temperatures were about 2.5 kelvins cooler and those of VEGA-1 about 4 kelvins warmer than temperatures measured by the Pioneer Venus Large Probe at these levels. Data taken by the VEGA-2 lander as it passed through the middle cloud agreed with those of the VEGA-2 balloon. Study of individual frames of the balloon data suggests the presence of multiple discrete air masses that are internally adiabatic but lie on slightly different adiabats. These adiabats, for a given balloon, can differ in temperature by as much as 1 kelvin at a given pressure. PMID- 17748085 TI - Implications of the VEGA Balloon Results for Venus Atmospheric Dynamics. AB - Both VEGA balloons encountered vertical winds with typical velocities of 1 to 2 meters per second. These values are consistent with those estimated from mixing length theory of thermal convection. However, small-scale temperature fluctuations for each balloon were sometimes larger than predicted. The approximate 6.5-kelvin difference in temperature consistently seen between VEGA-1 and VEGA-2 is probably due to synoptic or planetary-scale nonaxisymmetric disturbances that propagate westward with respect to the planet. There is also evidence from Doppler data for the existence of solar-fixed nonaxisymmetric motions that may be thermal tides. Surface topography may influence atmospheric motions experienced by the VEGA-2 balloon. PMID- 17748086 TI - Southern hemisphere origin of the cretaceous laytonville limestone of california. AB - New paleomagnetic, paleontologic, and stratigraphic data from outcrops of the Laytonville Limestone (101 to 88 million years old) support a Southern Hemisphere origin. A paleomagnetic megaconglomerate test is statistically significant and suggests magnetization at 14 degrees +/- 5 degrees south, predating Late Cretaceous to Eocene (70 to 50 million years ago) accretion. Rapid Kula plate movement or the existence and demise of a now vanished oceanic plate (or both) are required to accommodate the greater than 50 degrees of poleward displacement implied by the paleomagnetic data. This rapid motion brings into question the validity of a "speed limit" for absolute plate velocity based on present-day plate motions. PMID- 17748087 TI - Species interactions in ecology: community ecology. PMID- 17748088 TI - The Australian phanerozoic: phanerozoic Earth history of australia. PMID- 17748090 TI - Products & materials. PMID- 17748089 TI - Memory development: cognitive learning and memory in children. PMID- 17748092 TI - THOMAS JEFFERSON, THE SCIENTIST. PMID- 17748091 TI - CONTRIBUTIONS OF THE MEDICAL CORPS OF THE ARMY TO THE PUBLIC HEALTH LABORATORY. PMID- 17748093 TI - CHARLES SCHUCHERT 1858-1942. PMID- 17748094 TI - THE REPUBLICATION OF TECHNICAL BOOKS OF AXIS ORIGIN. PMID- 17748095 TI - A NEW SEISMOGRAPH IN MEXICO. PMID- 17748097 TI - RARE CHEMICALS. PMID- 17748096 TI - THE SOCIETY OF THE SIGMA XI. PMID- 17748098 TI - ISAIAH BOWMAN, PRESIDENT OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17748099 TI - A REPLY TO PROFESSOR WILLEM J. LUYTEN. PMID- 17748100 TI - THE EFFECT OF TRYPTOPHANE DEFICIENCY ON REPRODUCTION. PMID- 17748101 TI - INFLUENCE OF FEVER UPON THE ACTION OF 3,3'-METHYLENE-BIS-(4-HYDROXYCOUMARIN) (DICUMAROL). PMID- 17748102 TI - AN APPARATUS FOR CONCENTRATING SERUM. PMID- 17748103 TI - Educators as Such. PMID- 17748104 TI - Opening Government Records. PMID- 17748105 TI - North Dakota Geological Specimen in Nanking. PMID- 17748107 TI - Simian Temperament. PMID- 17748106 TI - Letter to the Editor. PMID- 17748108 TI - Reprints Again. PMID- 17748109 TI - Grassland Vegetation: Historical Note. PMID- 17748110 TI - Letter to the Editor. PMID- 17748111 TI - Referees: Credits and Demerits. PMID- 17748113 TI - Electricity in Volcanic Clouds: Investigations show that lightning can result from charge-separation processes in a volcanic crater. AB - In November of 1963 an oceanic volcano produced an island, Surtsey, just off the southern coast of Iceland. The volcanic crater was often flooded with sea water. Vigorous eruptions of steam and tephra were accompanied by an enhancement of the normal fine-weather potential gradient, and lightning was often observed. Measurements of atmospheric electricity and visual and photographic observations lead us to believe that the electrical activity is caused by the ejection from the volcano into the atmosphere of material carrying a large positive charge. The concentration of charge in the eruption plume as it issued from the orifice of the volcano is estimated to be of the order of 10(5) or 10(6) elementary charges per cubic centimeter. PMID- 17748112 TI - One-Sided Criticism of University Research. PMID- 17748114 TI - Women in Science: Why So Few?: Social and psychological influences restrict women's choice and pursuit of careers in science. AB - American society has prided itself on its concern for the fullest development of each individual's creative potential. As a nation, we have become sensitive to the social handicaps of race and class but have remained quite insensitive to those imposed because of sex. Those women who have entered the top professional fields have had to have extraordinary motivation, thick skins, exceptional ability, and some unusual pattern of socialization in order to reach their occupational destinations. In their backgrounds one is likely to find a professional mother, an unusually supportive father, or dedicated and stimulating teachers. PMID- 17748115 TI - Kansas City: New Medical Complex, University Should Complement Midwest Research Institute. PMID- 17748116 TI - Birth Control: Academy Report Stresses Burdens of High Birth Rate among the Impoverished Here. AB - In addition to the suggestions contained in the body of its report, the Academy population committee made several specific recommendations in three major spheres of activity-research, education and training, and services. Essentially the recommendations in all three areas can be summed up in a single word-"more." Specifically, in terms of research, the committee called for "all appropriate institutions, both private and governmental, to expand their efforts in the whole range of disciplines that contribute to knowledge of population matters, including demography, economics and other social sciences as well as biology, medicine and public health." PMID- 17748118 TI - Electron Spin Resonance Spectroscopy: Application to Proof of Structure of Organic Ketones. AB - Many ketones containing an alpha-methylene group can be converted to alpha diketone radical anions in dimethyl sulfoxide solution. The resulting radical anions can usually be unambiguously identified by electron spin resonance spectroscopy, and the structure of the starting ketone may be deduced, often without reference to model compounds. The technique is also applicable to alpha diketones, alpha-bromoketones, and alpha-hydroxyketones. PMID- 17748117 TI - Morphology and Sediments of a Portion of the Mid-Atlantic Ridge. AB - In October 1964, a detailed geophysical and sampling survey was made of the central part of the Mid-Atlantic Ridge between 22 degrees and 23 degrees north latitude. The results indicate a large difference in age between the relief of the crest and that of the flanks of the Ridge and suggest that the crest portion is very young. Detailed surveys of two sediment-filled valleys on the upper western flank of the Ridge reveal different sedimentary sequences in the two valleys and indicate the probable existence of a locally controlled depositional regime and a significant local supply of sediment. PMID- 17748119 TI - Terrestrial Heat Flow through Salt-Marsh Peat. AB - Two measurements of the temperature gradient in salt-marsh peat made at an interval of (1/2) year permit the upward flow of heat to be estimated as 1.37 x 10(-6) cal cm(-2) sec(-1). This value corresponds closely to the average terrestrial heat flow, obtained in mines and wells. PMID- 17748120 TI - Sulfur: A New High-Pressure Form. AB - Under high pressures and elevated temperatures, rhombic sulfur is converted to a new cubic form; this form was quenched at room temperature and pressure and studied by x-ray diffraction. Phase boundaries for this new form have been established. PMID- 17748121 TI - Late Glacial Ice-Wedge Casts in Northern Nova Scotia, Canada. AB - Ice-wedge casts in northern Nova Scotia and the relation of the casts to the outwash that contains them indicate that the ice wedges formed in a permafrost environment after the accumulation of the outwash. This permafrost environment is tentatively correlated with pollen zone L-3 of the Gillis Lake deposit, Cape Breton Island, Nova Scotia, and with the Valders time of the midcontinental sequence. PMID- 17748122 TI - Low Deuterium Content of Lake Vanda, Antarctica. AB - Lake Vanda in Victoria Land, Antarctica, is permanently ice-covered and permanently stratified, with warm, salty water near the bottom. Deuterium analyses of lake water from several levels indicate that the lake has a low deuterium content, and that it is stratified with respect to this isotope. This low deuterium content supports the evidence from the lake's ionic content that the saline layer is not of marine origin, and it indicates that evaporation from the ice surface has taken place. The stratification of the lake with respect to deuterium suggests that the upper and lower layers of water were formed at different times from different sources of glacial melt water. PMID- 17748123 TI - Aflatoxins: Environmental Factors Governing Occurrence in Spanish Peanuts. AB - Aflatoxins are absent from freshly harvested peanuts although Aspergillus flavus infest most of the kernels from pods having visible openings. Microbial competition, governed by kernel moisture, limits aflatoxin content of kernels. The toxins are subject to microbial breakdown but the amount broken down is governed by initial aflatoxin concentration. PMID- 17748124 TI - Fish Immunogenetics Research. PMID- 17748125 TI - SCIENCE AND THE RATIONAL ANIMAL. PMID- 17748126 TI - THE NAME, "SCRIPPS INSTITUTION OF OCEANOGRAPHY". PMID- 17748127 TI - POLLUTION OF THE CITY AIR AS A SOURCE OF NOSE AND THROAT DISTURBANCE. PMID- 17748128 TI - COLOR BLINDNESS IN TURKEY. PMID- 17748130 TI - ENVIRONMENTAL CONDITIONS AND THE WASTING DISEASE OF EEL-GRASS. PMID- 17748129 TI - SEXUAL DIMORPHISM OF HYMENOPTEROUS EGGS AND LARVAE. PMID- 17748132 TI - CONCENTRATION AND PARTIAL PURIFICATION OF BACTERIOPHAGE. PMID- 17748131 TI - REGARDING THE GENERAL NATURE OF CATHEPTIC ENZYMES. PMID- 17748133 TI - SIMPLE SYNCHRONOUS MOTOR FOR THE HARVARD KYMOGRAPH. PMID- 17748134 TI - VISIBLE FILE FOR LANTERN SLIDES. PMID- 17748135 TI - THE CULTURE OF A FREE-LIVING NEMATODE (GENUS RHABDITIS) AND ITS USE AS CLASSROOM MATERIAL. PMID- 17748136 TI - THE RUMFORD FUND OF THE AMERICAN ACADEMY OF ARTS AND SCIENCES. PMID- 17748138 TI - THE QUESTION AS TO WHETHER FALCONS WHEN SOARING INTERLOCK THEIR PRIMARY WING FEATHERS. PMID- 17748137 TI - CONTRIBUTIONS TO OUR KNOWLEDGE OF THE AERATION OF SOILS. PMID- 17748139 TI - THE CHROMOSOMES IN RELATION TO THE DETERMINATION OF SEX IN INSECTS. PMID- 17748141 TI - THE GEOGRAPHICAL DISTRIBUTION OF THE BELL-TOADS. PMID- 17748142 TI - A NEW ARMORED DINOSAUR FROM THE UPPER CRETACEOUS OF WYOMING. PMID- 17748140 TI - HYDRATION CAVES. PMID- 17748144 TI - BOTANICAL NOTES. PMID- 17748143 TI - A PRELIMINARY NOTE ON CLOVER DISEASES IN TENNESSEE. PMID- 17748145 TI - TECHNICAL EDUCATION IN AUSTRALIA. PMID- 17748146 TI - THE INSTALLATION OF PRESIDENT JAMES AT THE UNIVERSITY OF ILLINOIS. PMID- 17748147 TI - THE INAUGURATION OF PRESIDENT DRINKER. PMID- 17748148 TI - Hands and Brains. PMID- 17748149 TI - Letters to the Editor. PMID- 17748150 TI - Eradicating the Gypsy Moth. PMID- 17748151 TI - Ozone: Protection of Plants from Injury. PMID- 17748152 TI - Mature Scientists Need Support Too. PMID- 17748153 TI - Nevada Test Fallout. PMID- 17748154 TI - Moulton Hall. PMID- 17748155 TI - Distribution of Research Funds. PMID- 17748156 TI - National Goals and the University. PMID- 17748158 TI - Nobel Prize: 1963 Award Honors Three for Research on Nerve Functioning. PMID- 17748157 TI - The Coming Changes in American Science. PMID- 17748159 TI - UNESCO: Director General Stakes Out Broader Responsibilities In Applying Research to Development. PMID- 17748161 TI - Krebiozen: No Clinical Test, Says National Cancer Institute. PMID- 17748160 TI - A Lean Year for New Buildings:Congress Casts Critical Eyeon NASA, PHS Facilities Requests. PMID- 17748162 TI - Lymphocytic Choriomeningitis Infection in Neonataily Thymectomized Mice Bearing Diffusion Chambers Containing Thymus. AB - Normal, nonoperated Swiss mice which had been inoculated intracerebrally with lymphocytic choriomeningitis virus showed a 100-percent mortality within 8 days after virus challenge. Neonatally thymectomized mice, with or without empty intraperitoneal diffusion chambers, were protected from the lethal effects of the virus, with no animals dying within 14 days after inoculation. Cell-tight Millipore diffusion chambers containing newborn thymic tissue, implanted intraperitoneally into neonatally thymectomized mice, restored the susceptibility of 52 percent of these mice to the lethality of the virus infection. The percentage restoration with subcutaneous thymic grafting was similar. A humoral mechanism of action of the tissue in the chamber is proposed. PMID- 17748163 TI - Thermoperiodism in Sea-run Cutthroat Trout ( Salmo clarki clarki). AB - Thermal tolerances from square-wave cycled temperature acclimation were compared with those from constant acclimation temperatures. A response to the maximum temperature of the square-wave cycle occurred. The acclimation thermoperiod was varied from one-fourth to twice the 24-hour cycle, and a relative maximum of tolerance resulted for the 24-hour thermoperiod. This suggests physiological adaption to natural 24-hour thermoperiods. PMID- 17748164 TI - An Experiment in Hurricane Modification: Preliminary Results. PMID- 17748165 TI - Particle Sorting by Repeated Freezing and Thawing. AB - If a hetrogeneous mixture of particles of various sizes is frozen and thawed repeatedly, the particles are sorted into relatively uniformn groups by size. The movement of particles depends on the amount of water between the ice-water interface and the particle, the rate of freezing, the distribution of the particles by size, and the orientation of the freeze-thaw plane. PMID- 17748167 TI - 1,4-Benzoquinone Tetracarboxylic Acid Dianhydride, C1008:A Strong Acceptor. AB - This exceptionally reactive compound 1,4-benzoquinone tetracarboxylic acid dianhydride is one of the strongest vr-acids yet described. PMID- 17748166 TI - Sodium Perxenate Hexahydrate. AB - Sodidm perxenate hexahydrate ( NatXeO6.6H: O) has been identified from study of its crystal structure by x-ray diffraclion. The perxenate ion( XeO64) has the shape of a regular octahedron with the Xe-O bond distance 1.84 A. PMID- 17748168 TI - Radiation Damage to Artemia Cysts:Effects of Water Vapor. AB - Water vapor altered the form and greatly increased the rate of decay of the electron-spin resonance pattern of long-lived free radicals obtained upon gamma irradiation of Artemia salina cysts ( brine shrimp eggs). These results, combined with data on radiation survival, indicate that the water vapor protects the cysts from radiation damage, or heals the damage. They also indicate that water protects the cysts from the effect of oxygen by neutralizing the radiation induced free radicals before they can interact with oxygen to produce irreversible damage. PMID- 17748169 TI - Very-Low-Frequency Radio Waves and the Ionosphere. PMID- 17748170 TI - Radioiodine: Its Nature and Effects. PMID- 17748171 TI - The Witness for Science. PMID- 17748172 TI - News of Science. PMID- 17748173 TI - Systemic Control of Cherry Leaf-Spot Fungus by Foliar Sprays of Actidione Derivatives. PMID- 17748174 TI - Lengthening the Carbon Chain of Sugars. PMID- 17748176 TI - Miscellaneous Publications. PMID- 17748175 TI - Increased Oxidative Effects on Irradiation in Glass. PMID- 17748179 TI - THE CONTINENTAL DYNAMO. PMID- 17748178 TI - Scientific Meetings. PMID- 17748180 TI - BALL ELECTRIC-LIGHTING SYSTEM. PMID- 17748181 TI - SCIENTIFIC NEWS IN WASHINGTON. PMID- 17748182 TI - The Geological Survey. PMID- 17748183 TI - Diseases of Menagerie Animals. PMID- 17748184 TI - COMMERCIAL GEOGRAPHY. PMID- 17748186 TI - THE ELECTRIC LIGHT IN LAND WARFARE. PMID- 17748185 TI - HEALTH MATTERS. PMID- 17748187 TI - ELECTRIC LIGHT AND EYES. PMID- 17748189 TI - THE DAFT MOTOR ON THE ELEVATED ROADS. PMID- 17748188 TI - ELECTRICAL NEWS. PMID- 17748190 TI - THE EDISON LAMP PATENTS IN ENGLAND. PMID- 17748191 TI - AN ELECTRIC ROAD FOR CHATTANOOGA. PMID- 17748192 TI - Two Discoveries in Human Osteology by the Hemenway Expedition. PMID- 17748193 TI - The Julien Electric Traction System. PMID- 17748194 TI - The Soaring of Birds. PMID- 17748195 TI - Color-Blindness. PMID- 17748196 TI - Various Definitions of Manual Training. PMID- 17748197 TI - Color of Katy-did. PMID- 17748198 TI - The Great Lake Basins of the St. Lawrence. PMID- 17748199 TI - STORAGE OF STORM-WATERS ON THE GREAT PLAINS. PMID- 17748200 TI - A BOTANICAL LABORATORY. PMID- 17748201 TI - THE SOPHISTICATED FRENCH WINES. PMID- 17748202 TI - THE DISTRIBUTION OF FISHES. PMID- 17748203 TI - THE PATENT OFFICE BUILDING. PMID- 17748204 TI - THE STRUCTURE OF THE HEMIPTEROUS MOUTH. PMID- 17748205 TI - THE ETYMOLOGY OF THE TWO IROQUOIAN COMPOUND STEMS, -SKEN,-RA-KEQ''-TE'' AND -NDU TA-KEQ''- TE''. PMID- 17748206 TI - FORTHCOMING SCIENTIFC BOOKS. PMID- 17748207 TI - The Bacillus of Influenza. PMID- 17748208 TI - The Question of the Celts. PMID- 17748209 TI - MODERN ZOOLOGY. PMID- 17748210 TI - BIOLOGICAL ABSTRACTS. PMID- 17748211 TI - THE INTERNATIONAL UNION OF PURE AND APPLIED CHEMISTRY. PMID- 17748212 TI - THE NEED OF GERMAN SCIENTIFIC MEN. PMID- 17748213 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17748214 TI - FURTHER OBSERVATIONS ON THE SEX CHROMOSOMES OF MAMMALS. PMID- 17748215 TI - SCORPIONS IN NORTH DAKOTA. PMID- 17748216 TI - A NEW OCCURANCE OF THE BLACK-EYED YELLOW MUTATION IN RATS. PMID- 17748217 TI - THE OHIO ACADEMY OF SCIENCE. PMID- 17748218 TI - Can We Curb the Irresponsibles? PMID- 17748219 TI - Hemolytic Streptococcal Sore Throat: Antibody Response Following Treatment With Penicillin, Sulfadiazine, and Salicylates. PMID- 17748220 TI - Blood Levels of Penicillin After Oral Administration With Various Antacids. PMID- 17748221 TI - Studies on the Toxicity of Streptomycin for Man: A Preliminary Report. AB - In this limited experience, tests of renal and hepatic function together with blood studies before and after the parenteral administration of streptomycin revealed no evidence of serious toxicity. Reactions, consisting of fever, arthralgias, and skin rashes as well as histamine-like effects, are believed to be due to impurities retained in the preparations of streptomycin employed in these studies. PMID- 17748222 TI - Complement-fixing and Neutralizing Antibodies Against Japanese B Virus in the Sera of Okinawan Horses. PMID- 17748223 TI - The Absorption of Orally Administered Penicillin. PMID- 17748224 TI - Effect of Penicillin on Growth of Alcaligenes fecalis. PMID- 17748225 TI - Intravenous Utilization of Partial Acid Hydrolysates of Proteins. PMID- 17748226 TI - The Presence in Normal Serum of Inhibiting Substances Against Bacillus subtilis. AB - Sera from 35 normal persons who had received no previous medication were tested for inhibiting substances against Bacillus subtilis and Staphylococcus aureus. Thirty of the sera (85 per cent) inhibited Bacillus subtilis in dilutions varying up to 1:32, but in no instance was Staphylococcus aureus inhibited. The data presented would indicate that Bacillus subtilis is not a suitable organism for use in the assay of antibiotics in the presence of serum. PMID- 17748227 TI - Preliminary Studies on the Absorption and Excretion of Streptomycin in Dogs. AB - Streptomycin varying in potency from 100 to 500 units/mg. has been administered to 14 dogs intravenously, intramuscularly, and orally in amounts of 100,000 to 420,000 units. High blood levels of streptomycin were observed after parenteral administration and 23 to 65 per cent was excreted in the urine of normal dogs. After 4 or 5 hours only small amounts were detected in the blood. The maintenance of blood levels was no better with intramuscular than with intravenous administration. Following the oral administration of as much as 420,000 units of streptomycin, it could not be detected in the plasma, but up to 3.9 per cent was recovered from the urine. PMID- 17748228 TI - The Activity of Streptomycin in Experimental Syphilis. PMID- 17748229 TI - Science Exhibition. PMID- 17748230 TI - Federal Aid for Scientific Research. PMID- 17748233 TI - Competition Between Two Entomogenous Bacteria. PMID- 17748231 TI - Broadcasting Congressional Sessions. PMID- 17748232 TI - A Plea for Stabilized Progress. PMID- 17748234 TI - Radio Echoes From the Planets. PMID- 17748236 TI - Relief Packages for Scientific Workers in Western Europe. PMID- 17748235 TI - In Support of a September Meeting of the AAAS. PMID- 17748237 TI - THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE THE POPULAR CONCEPTION OF THE SCIENTIFIC MAN AT THE PRESENT DAY. PMID- 17748238 TI - THE PROBLEM OF THE METALLIFEROUS VEINS. PMID- 17748239 TI - ON THE HUMAN ORIGIN OF THE SMALL MOUNDS OF THE LOWER MISSISSIPPI VALLEY AND TEXAS. PMID- 17748240 TI - ISOLATION AND EVOLUTION. PMID- 17748242 TI - CO-OPERATION ON THE CONTINENT OF EUROPE. PMID- 17748241 TI - THE TERMINOLOGY OF ABERRANT CHROMOSOMES AND THEIR BEHAVIOR IN CERTAIN HEMIPTERA. PMID- 17748243 TI - THE STONE AGES IN TUNIS. PMID- 17748245 TI - MENTAL SCIENCE. PMID- 17748244 TI - CHILLED ARMOR FOR LAND-DEFENCES. PMID- 17748246 TI - Experimental Physics for Schools. PMID- 17748247 TI - Romantic Love and Personal Beauty. PMID- 17748248 TI - The Study of Geography. PMID- 17748250 TI - The Blair Educational Bill. PMID- 17748249 TI - Wind Pressure and Velocity. PMID- 17748251 TI - Privileged communication. PMID- 17748252 TI - Carcinogens and regulation. PMID- 17748253 TI - Science education: rhetoric and reality. PMID- 17748254 TI - The origin of man. AB - Five characters separate man from other hominoids-a large neocortex, bipedality, reduced anterior dentition with molar dominance, material culture, and unique sexual and reproductive behavior. Evidence provided by the fossil record, primate behavior, and demographic analysis shows that the traditional view that early human evolution was a direct consequence of brain expansion and material culture is incorrect, and that the unique sexual and reproductive behavior of man may be the sine qua non of human origin. PMID- 17748255 TI - Using materials science. AB - The science of the solid state has joined nuclear science and molecular biology as a field of major importance in the latter half of the 20th century. It took particular shape during the genesis of solid-state electronics and the post transistor era of integrated circuits for telecommunications, computers, and digital signal machines. However, these developments were soon joined by techniques from the ancient fields of metallurgy and ceramics and contributions from the more current fields of synthetic polymers, rubbers, plastics, and modified bioorganic substances. This vast realm was characterized by a National Academy of Sciences study of the 1970's as "materials science and engineering." The public, as well as the scientific and engineering community, are currently concerned about the uses of research and development and the applications of knowledge for national progress. Consideration is given here to how well we are using the science of materials for industrial strength and such governmental objectives as national security and energy economy. PMID- 17748256 TI - Eastern bloc evades technology embargo. PMID- 17748257 TI - Epidemiologists try to help stop more atlanta murders. PMID- 17748259 TI - Dump delaney clause, schweiker suggests. PMID- 17748258 TI - White sands, warm winds, and ...Toxic wastes? PMID- 17748260 TI - AAAS in Canada Seeks Peace Without Hawks. PMID- 17748261 TI - Development advocate to head interior. PMID- 17748262 TI - Mount st. Helens and a climate quandary. PMID- 17748263 TI - Ancient cut marks reveal work of prehuman hands. PMID- 17748264 TI - Is longevity a positive selection? PMID- 17748265 TI - Genetic link with human behavior causes stir. PMID- 17748267 TI - Confluence in research. PMID- 17748266 TI - The field of geography. PMID- 17748268 TI - Views of wundt. PMID- 17748270 TI - A pleistocene sand sea on the alaskan arctic coastal plain. AB - A ridge and thermokarst-basin landscape that is strikingly portrayed in Landsat winter imagery consists of large Pleistocene dunes that have been modified by younger eolian activity and thermokarst processes. This is the most extensive area of large stabilized dunes yet reported in the North American Arctic; the landscape is of particular interest because it has been proposed as a first-order analog for martian fretted terrain. Recognition of the large dunes permits a new interpretation for linear and curvilinear trends visible in Landsat summer imagery. PMID- 17748269 TI - Nitrogen processes. PMID- 17748271 TI - Noble gases in stratospheric dust particles: confirmation of extraterrestrial origin. AB - Noble gas elemental and isotopic ratios were measured in a group of 13 "chondritic" stratospheric dust particles. Neon and argon are present in "solar" proportions; xenon appears to be dominated by contributions from "planetary" sources. The apparent xenon concentration is higher than that measured in any bulk meteorite, approaching the concentration found in the noble gas-rich, acid insoluble residues from carbonaceous chondrites. PMID- 17748272 TI - Solar cycle signal in Earth rotation: nonstationary behavior. AB - Following the discovery of the 11-year solar cycle signal in earth rotation, linear techniques were employed to investigate the amplitude and phase of the difference between ephemeris time and universal time (DeltaT) as a function of time. The amplitude is nonstationary. This difference was related to Delta(LOD), the difference between the length of day and its nominal value. The 11-year term in Delta(LOD) was 0.8 millisecond at the close of the 18th century and decreased below noise level from 1840 to 1860. From 1875 to 1925, Delta(LOD) was about 0.16 millisecond, and it decreased to about 0.08 millisecond by the 1950's. Except for anomalous behavior from 1797 to 1838, DeltaT lags sunspot numbers by 3.0 +/- 0.4 years. Since DeltaT lags Delta(LOD) by 2.7 years, the result is that Delta(LOD) is approximately in phase with sunspot numbers. PMID- 17748273 TI - Scheiner's Halo: Evidence for Ice Ic in the Atmosphere. AB - Refraction of sunlight at the angle of minimum deviation between octahedral faces of crystals of ice Ic in the upper atmosphere could produce a halo around the sun or the moon at 27.46 degrees . Crystals of hexagonal ice having low-index faces cannot produce a halo of this radius. It is therefore suggested that Scheiner's halo, which has been reported at least four times since 1629 at 28 degrees from the sun, is due to ice Ic. If this is correct, it is apparently the first evidence that ice Ic occurs naturally and that liquid water can freeze to ice Ic. PMID- 17748274 TI - Natural disturbance and the steady state in high-altitude balsam fir forests. AB - Wind-induced, cyclic waves of death, regeneration, and maturation constantly move through the high-altitude balsam fir forests in the northeastern United States. Biomass and productivity relations, species diversity, and nutrient cycling patterns are closely tied to this cycle of disturbance. Disturbance is thus an integral part of the long-term maintenance of this ecosystem. Since forests of this type normally include all phases of the disturbance-regeneration cycle, they may constitute a steady-state ecosystem in equilibrium with the surrounding environment. PMID- 17748275 TI - Food dyes and impairment of performance in hyperactive children. PMID- 17748276 TI - PRODUCTS and MATERIALS. PMID- 17748278 TI - JOHN OTTERBEIN SNYDER. PMID- 17748277 TI - MINERALS SHARE' IN THE WAR. PMID- 17748279 TI - THE ACADEMY OF SCIENCES OF THE U.S.S.R. PMID- 17748280 TI - THE DIRECTOR OF RESEARCH OF THE WELLCOME FOUNDATION. PMID- 17748281 TI - MELLON INSTITUTE TECHNOCHEMICAL LECTURES, 1943-1944. PMID- 17748283 TI - CENTENNIAL OF THE OBSERVATORY OF THE UNIVERSITY OF CINCINNATI. PMID- 17748282 TI - LIMITATION ORDER L-144. PMID- 17748284 TI - THE AMERICAN-SOVIET SCIENTIFIC CONGRESS. PMID- 17748285 TI - ELEMENTS OF THE GENERALITY OF THE GROUP CONCEPT. PMID- 17748286 TI - PROTEIN CONCENTRATES FROM GRASSES. PMID- 17748287 TI - WHY THE KILGORE BILL? PMID- 17748288 TI - INFLUENCE OF ADRENAL CORTICAL SECRETION ON BLOOD ELEMENTS. PMID- 17748289 TI - THE NATURAL OCCURRENCE OF RIBOFLAVIN DEFICIENCY IN THE EYES OF DOGS. AB - In four dogs, the diarrhea, increased salivation and mucous membrane lesions characteristic of blacktongue were relieved within 24 hours following the administration of 150 mgs nicotinic amide, whereas the lacrimation, photophobia and extreme injection of the eye vessels did not diminish. These severe eye lesions regressed greatly 24 hours after the injection of 50 mgs of riboflavin, and in 72 hours had disappeared. The simultaneous occurrence of nicotinic acid and riboflavin deficiency in four dogs is evidence that such deficiencies occur as mixed diseases rather than as single entities. These findings are further evidence of the universality of nutritional deficiencies, since they suggest that deficiency diseases among the pets of families with deficiency diseases are not uncommon. In at least one instance the finding of nutritional deficiencies in a dog eating scraps from the family table led to a better understanding of the ill health of the family, none of whom had diagnostic lesions of deficiency disease at the time, although they all complained of weakness, nervousness, irritability and loss of appetite-the vague and ill-defined symptoms characteristic of deficiency diseases in the early stages. PMID- 17748290 TI - IDENTITY OF A LETHAL AGENT IN BROTH FILTRATES OF HEMOLYTIC STREPTOCOCCI WITH ERYTHROGENIC TOXIN. PMID- 17748291 TI - DEANTIGENATED BEEF BLOOD PLASMA AS A POSSIBLE SUBSTITUTE FOR HUMAN BLOOD PLASMA. PMID- 17748292 TI - This week in science. PMID- 17748293 TI - The trade deficit. PMID- 17748294 TI - Erratum. AB - In Eliot Marshall's article "California's debate on carcinogens" (News & Comment, 20 Mar., p. 1459), the last sentence of the third paragraph, which refers to fines to be imposed under Proposition 65, should have read, "Companies found guilty of violating it will be charged $2500 a day and legal costs." The article gave the incorrect figure of "$25,000 a day." PMID- 17748295 TI - Stereo viewing. PMID- 17748297 TI - Female Math Anxiety on the Wane: But data from standardized achievement tests in math and science still show male superiority, particularly among the highest scorers. PMID- 17748296 TI - Soviets Disinvited to Join Drilling Program: An invitation to join the international Ocean Drilling Program has been withdrawn because of objections by DOD. PMID- 17748298 TI - Academy rejects huntington nomination. PMID- 17748299 TI - NAS Elects New Members. PMID- 17748300 TI - Yb or Not Yb? That Is The Question: One rare earth element was substituted for another in manuscripts of two key papers, confusing some who wanted to get a head start on making superconducting compounds. PMID- 17748301 TI - Superconductor race heats up. PMID- 17748303 TI - Two committees vote to mothball the N reactor. PMID- 17748302 TI - Mars observer: still 1992. PMID- 17748304 TI - Shapiro to leave michigan for princeton. PMID- 17748305 TI - Asteroid Impact Gets More Support: The global distribution of shocked quartz at the Cretaceous-Tertiary boundary argues for an asteroid or comet impact and against a volcano as a cause of the mass extinction. PMID- 17748306 TI - Beyond the k-T boundary. PMID- 17748307 TI - Glasnost Comes to Soviet Physics: An article in the magazine Literaturnaya Gazeta publicizes a decade-long misdirection of high-pressure physics research and has some barbed words for the way Soviet science works. PMID- 17748308 TI - Some concepts in reaction dynamics. AB - The objective in this work has been one which I have shared with the two other 1986 Nobel lecturers in chemistry, D. R. Herschbach and Y. T. Lee, as well as with a wide group of colleagues and co-workers who have been responsible for bringing this field to its current state. That state is summarized in the title; we now have some concepts relevant to the motions of atoms and molecules in simple reactions, and some examples of the application of these concepts. We are, however, richer in vocabulary than in literature. The great epics of reaction dynamics remain to be written. I shall confine myself to some simple stories. PMID- 17748309 TI - Shocked quartz in the cretaceous-tertiary boundary clays: evidence for a global distribution. AB - Shocked quartz grains displaying planar features were isolated from Cretaceous- Tertiary boundary clays at five sites in Europe, a core from the north-central Pacific Ocean, and a site in New Zealand. At all of these sites, the planar features in the shocked quartz can be indexed to rational crystallographic planes of the quartz lattice. The grains display streaking indicative of shock in x-ray diffraction photographs and also show reduced refractive indices. These characteristic features of shocked quartz at several sites worldwide confirm that an impact event at the Cretaceous-Tertiary boundary distributed ejecta products in an earth-girdling dust cloud, as postulated by the Alvarez impact hypothesis. PMID- 17748310 TI - Polychlorinated biphenyl dechlorination in aquatic sediments. AB - The polychlorinated biphenyl (PCB) residues in the aquatic sediments from six PCB spill sites showed changes in PCB isomer and homolog (congener) distribution that indicated the occurrence of reductive dechlorination. The PCB dechlorinations exhibited several distinct congener selection patterns that indicated mediation by several different localized populations of anaerobic microorganisms. The higher (more heavily chlorinated) PCB congeners that were preferentially attacked by the observed dechlorination processes included all those that are either pharmacologically active or persistent in higher animals. All the lower (less heavily chlorinated) PCB congeners formed by the dechlorinations were species that are known to be oxidatively biodegradable by the bacteria of aerobic environments. PMID- 17748311 TI - Calcium-41 concentration in terrestrial materials: prospects for dating of pleistocene samples. AB - Calcium-41 has been suggested as a new tool for radiometric dating in the range of 10(5) to 10(6) years. The concentration of cosmogenic calcium-41 in natural samples of terrestrial origin has now been determined by high-sensitivity accelerator mass spectrometry after pre-enrichment in calcium-41 with an isotope separator. Ratios of calcium-41 to total calcium between 2 x 10(-14) and 3 x 10( 15) were measured for samples of contemporary bovine bone and from limestone deposits. Some prospects for the use of calcium-41 for dating Middle and Late Pleistocene bone and for other geophysical applications are discussed. PMID- 17748312 TI - Chinese botany: science and civilisation in china. PMID- 17748313 TI - Interactive behaviors: altruism and aggression. PMID- 17748314 TI - Planetary evolution: atmospheres and ionospheres of the outer planets and their satellites. PMID- 17748316 TI - Products & materials. PMID- 17748315 TI - Kimberlite geology: kimberlites. PMID- 17748317 TI - MEDALLISTS OF THE ROYAL SOCIETY. PMID- 17748319 TI - DAYTON C. MILLER AND THE POPULARIZATION OF SCIENCE. PMID- 17748318 TI - EACH AFTER HIS KIND. PMID- 17748320 TI - TRAINING PHYSICIANS FOR GREAT BRITAIN. PMID- 17748321 TI - GIFT TO THE ROYAL SOCIETY BY THE AMERICAN PHILOSOPHICAL SOCIETY. PMID- 17748322 TI - THE AMERICAN MUSEUM OF HEALTH. PMID- 17748323 TI - RESEARCH LABORATORY OF THE STANDARD OIL COMPANY. PMID- 17748324 TI - THE CHICAGO MEETING OF THE FEDERATION OF AMERICAN SOCIETIES FOR EXPERIMENTAL BIOLOGY. PMID- 17748326 TI - ANOTHER NOTE ON THE ISOSTATIC CONTROL OF FLUCTUATIONS OF SEA LEVEL. PMID- 17748325 TI - THE TWENTIETH ANNIVERSARY OF THE DIVISION OF PETROLEUM CHEMISTRY OF THE AMERICAN CHEMICAL SOCIETY. PMID- 17748327 TI - THE POSSIBILITIES OF SYSTEMIC INFECTION WITH DERMATITIS-PRODUCING SCHISTOSOMES. PMID- 17748329 TI - A CLOTTING FACTOR IN RABBIT PLASMA. PMID- 17748328 TI - LITTLE KNOWN ENEMIES OF YOUNG OYSTERS. PMID- 17748330 TI - A CASEIN DIGEST BY VEIN UTILIZED TO FORM BLOOD PLASMA PROTEIN. PMID- 17748331 TI - AFFILIATED ACADEMIES OF SCIENCE. PMID- 17748332 TI - THE CYANIDE STABLE RESPIRATION OF THE SEA URCHIN EGG. PMID- 17748333 TI - REDUCTION IN THE BLOOD PRESSURES OF RENAL HYPERTENSIVE DOGS WITH HOG RENIN. PMID- 17748334 TI - SPIRIT BLUE AGAR: A MEDIUM FOR THE DETECTION OF LIPOLYTIC MICROORGANISMS. PMID- 17748336 TI - This week in science. PMID- 17748335 TI - AN IMPROVED METHOD OF APPLYING COLORED PENCILS. PMID- 17748337 TI - High-energy astrophysics. PMID- 17748338 TI - Corrections and clarifications. AB - In the report "The drift of Saturn's north polar spot observed by the Hubble Space Telescope" by J. Caldwell et al. (16 Apr., p. 326), the revised System III rotation rate of the drift was incorrectly calculated. It should not have been "810.737 degrees +/- 0.008 degrees per day," as stated (line 21, col. 1, p. 329), but rather "810.851 degrees +/-0.008 degrees per day." PMID- 17748339 TI - Basic research and weather prediction. PMID- 17748340 TI - Sciencescope. PMID- 17748341 TI - Scientists count a rising tide of whales in the seas. PMID- 17748342 TI - Neutrino watchers go to extremes. PMID- 17748343 TI - Seeing the nuclei of active galaxies. PMID- 17748344 TI - Recent Advances of X-ray Astronomy. PMID- 17748345 TI - The case of the blue stragglers. PMID- 17748346 TI - Geminga and the astronomy of isolated neutron stars. PMID- 17748347 TI - Taking stock of gamma ray bursts. PMID- 17748348 TI - Astrophysical opacity. AB - An array of problems in astronomy, cosmology, and particle physics is dependent on our understanding of the evolution and structure of stars. Stellar structure and evolution, in turn, depend on how the nuclear energy generated in the stellar center is transported to the surface. Energy transport by photons is a primary transfer mechanism. Recent improvements in the calculation of the radiative properties of stellar matter have helped resolve several long-standing discrepancies between observations and the predictions of theoretical models. PMID- 17748349 TI - Patterned condensation figures as optical diffraction gratings. AB - Heterogeneous, patterned surfaces comprising well-defined hydrophobic and hydrophilic regions and having micrometer-scale periodicities were prepared by patterning the adsorption of omega-functionalized alkanethiolates in self assembled monolayers (SAMs) on gold. Condensation of water on such surfaces resulted in drops that followed the patterns in the SAMs. These patterned condensation figures (CFs) acted as optical diffraction gratings for reflected (or transmitted) light from a helium-neon laser (wavelength of 632.8 nanometers). Under an atmosphere of constant relative humidity, the development of the condensation figure was monitored quantitatively, as the temperature of the surface was lowered, by following the change in intensity of a first-order diffraction spot. This experimental technique may be useful in the development of new types of optical sensors that respond to their environment by changing the reflectivity of patterned regions and for studying phenomena such as drop nucleation, contact angle hysteresis, and spontaneous dewetting and break-up of thin liquid films. PMID- 17748350 TI - New light on the heart of darkness of the solar chromosphere. AB - Solar carbon monoxide spectra indicate the existence of a cool (less than 4000 kelvin) component to the solar chromosphere coexisting with the hot, bright gas at 6000 to 7000 kelvin. However, both the existence and the location of the cool component have been controversial. New high-resolution spectra show that carbon monoxide goes into emission just beyond the limb, allowing it to be probed without photospheric contamination. The cool component has temperatures as low as 3000 to 3500 kelvin and appears to cover 50 to 85 percent of the quiet solar surface. There is a steep temperature rise to normal chromospheric temperatures at a height of 900 to 1100 kilometers. Large horizontal velocities are seen, suggesting that the cool component is maintained by the supersonic adiabatic expansion of upwelling gas in overshooting granules. PMID- 17748351 TI - Void structure in colloidal dispersions. AB - The time evolution of void structures in highly purified polymer latex dispersions was studied with a confocal laser scanning microscope. In such dispersions, which were initially homogeneous, the voids grew with time when the dispersions were kept standing and formed more quickly in the internal material than in material close to the glass-dispersion interface. Void formation is thus not an artifact arising from the presence of the interface. A similar structural inhomogeneity, in apparently homogeneous systems, is discussed for simple ionic solutions, ionic polymer solutions, and Langmuir-Blodgett films. PMID- 17748352 TI - Synthesis and Characterization of Molybdenum Carbide Clusters MonC4n, (n = 1 to 4). AB - Laser radiation (XeCl laser, 308-nanometer wavelength) focused into a cell containing Mo(CO)(6) vapor produced ultrafine particles in the extended waist of the laser beam. Negative ion mass spectrometry revealed molybdenum carbide cluster ions with a stoichiometry MonC4n (n = 1 to 4). The MonC4n(-) (n = 2 to 4) ions are completely unreactive with NH(3), H(2)O, and O(2), suggesting structures in which the molybdenum atoms are unavailable for coordination to additional ligands. Collision-induced dissociation studies of these anions show the loss of MoC(4) units as the main fragmentation pathway. This observation, together with the lack of addition reactions, provides a basis for structures in which a planar cluster of two, three, or four molybdenum atoms is surrounded by, and bonded to, carbon dimers. PMID- 17748353 TI - Do hydrofluorocarbons destroy stratospheric ozone? AB - Hydrofluorocarbons, many of which contain a CF(3) group, are one of the major substitutes for the chlorofluorocarbons and halons that are being phased out because they contribute to stratospheric ozone depletion. It is critical to ensure that CF(3) groups do not cause significant ozone depletion. The rate coefficients for the key reactions that determine the efficiency of the CF(3) radical as a catalyst for ozone loss in the stratosphere have been measured and used in a model to calculate the possible depletion of ozone. From these results, it is concluded that the ozone depletion potentials related to the presence of the CF(3) group in hydrofluorocarbons are negligibly small. PMID- 17748354 TI - Response. PMID- 17748356 TI - Cold fusion revisited. PMID- 17748355 TI - Theory, experiment, and the h + d2 reaction. PMID- 17748357 TI - Telescope builders. PMID- 17748358 TI - Inbreeding and evolution. PMID- 17748359 TI - Auditory cognition. PMID- 17748360 TI - Vignettes: mentoring. PMID- 17748361 TI - Products & materials. PMID- 17748362 TI - AN EVALUATION OF THE FACTORS RESPONSIBLE FOR PUBLIC HEALTH PROGRESS IN THE UNITED STATES. PMID- 17748364 TI - MARSH GAS IN THE ECOLOGY OF SOME PEAT-BOGS. PMID- 17748363 TI - MICRO-COPEPODA IN MARINE PHYTOPLANKTON CATCHES. PMID- 17748365 TI - THE CONFIGURATION OF GLUTAMIC ACID FROM SCARLET FEVER ANTITOXIN. PMID- 17748366 TI - PATENTS FOR CHEMICAL COMPOUNDS. PMID- 17748367 TI - LUCITE. PMID- 17748369 TI - THE EFFECT OF CERTAIN CHEMICALS ON THE HATCHING OF MOSQUITO EGGS. PMID- 17748368 TI - THE VIRGINIA ACADEMY OF SCIENCE. PMID- 17748370 TI - THE KENTUCKY ACADEMY OF SCIENCE. PMID- 17748372 TI - RECOVERY OF THE VIRUS OF EQUINE ENCEPHALOMYELITIS (WESTERN TYPE) FROM HUMAN BLOOD SERUM. PMID- 17748371 TI - AN OBSERVATION SUGGESTING THE PRESENCE OF A GONADOTROPIC HORMONE IN ROYAL JELLY. PMID- 17748373 TI - ENCEPHALOMYELITIS IN MONKEYS. PMID- 17748374 TI - A HIGH RESOLVING POWER ULTRACENTRIFUGE. PMID- 17748375 TI - A SMALL HYGROMETER. PMID- 17748376 TI - SPECIALIZATION IN EDUCATION. PMID- 17748377 TI - THE LIMITS OF SCIENCE. PMID- 17748379 TI - THE RELATION OF LIME AND MAGNESIA TO METABOLISM. PMID- 17748378 TI - INDIAN POTTERY. PMID- 17748380 TI - NOTES ON THE EVIDENCES OF HUMAN REMAINS FROM JACOBS CAVERN. PMID- 17748381 TI - NEW TERMS IN CHEMISTRY. PMID- 17748382 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17748383 TI - RADIUM AND CANCER. PMID- 17748384 TI - THE RHODES SCHOLARSHIPS. PMID- 17748386 TI - POST-WAR MILITARY RESEARCH. PMID- 17748385 TI - REHABILITATION AND THE COLLEGE CURRICULUM IN BIOLOGY. PMID- 17748387 TI - CHARLES B. LIPMAN 1883-1944. PMID- 17748389 TI - THE DEPARTMENT OF GEOLOGY AND PALEONTOLOGY OF THE AMERICAN MUSEUM OF NATURAL HISTORY. PMID- 17748388 TI - THE INDUSTRIAL DEVELOPMENT OF INDIA. PMID- 17748390 TI - THE INSTITUTE OF GEOPHYSICAL TECHNOLOGY AT ST. LOUIS UNIVERSITY. PMID- 17748392 TI - THE OPPORTUNITY OF PURE SCIENCE. PMID- 17748391 TI - BIOCHROMES. PMID- 17748393 TI - EDUCATION IN ARGENTINA. PMID- 17748394 TI - PREVENTION AND TREATMENT OF d-TUBOCURARINE POISONING. PMID- 17748395 TI - THE LEVEL OF PERFORMANCE IN THE WHITE RAT. PMID- 17748396 TI - INHIBITION OF E. COLI BY PENICILLIN. PMID- 17748398 TI - COMMENT AND CRITICISM. PMID- 17748397 TI - TOXICITY OF DICHLORO-DIPHENYL-TRICHLORETHANE (DDT) TO GOLDFISH AND FROGS. PMID- 17748399 TI - THE POSITION OF EMIN PASHA. PMID- 17748400 TI - THE MEETING OF THE ECONOMIC AND HISTORICAL ASSOCIATIONS. PMID- 17748401 TI - INTERNATIONAL STATISTICAL INSTITUTE. PMID- 17748402 TI - HEALTH MATTERS. PMID- 17748403 TI - MENTAL SCIENCE. PMID- 17748404 TI - EXPLORATION AND TRAVEL. PMID- 17748406 TI - The Sonora earthquake. PMID- 17748405 TI - The cause of consumption. PMID- 17748407 TI - A noteworthy specimen of Devonian lepidodendron. PMID- 17748408 TI - A needed invention in coal-mining. PMID- 17748409 TI - Bassariscus, a new generic name in mammalogy. PMID- 17748410 TI - INVESTIGATIONS AT THE NUTRITION LABORATORY OF THE CARNEGIE INSTITUTION OF WASHINGTON, BOSTON, MASSACHUSETTS. PMID- 17748411 TI - NEANDERTAL MAN IN SPAIN: THE LOWER JAW OF BANOLAS. PMID- 17748414 TI - A CHICKEN WITH FOUR LEGS. PMID- 17748412 TI - CALIFORNIA MEETING OF THE GEOLOGICAL SOCIETY OF AMERICA. PMID- 17748413 TI - APPLICATION OF PETROGRAPHIC METHODS TO ANALYTICAL CHEMISTRY. PMID- 17748415 TI - A CORRECTION. PMID- 17748416 TI - TO THE AMERICAN PHYSICAL SOCIETY. PMID- 17748417 TI - THE DIFFUSION OF GASES AT LOW PRESSURES MADE VISIBLE BY COLOR EFFECTS. PMID- 17748418 TI - THE NEW ORLEANS MEETING OF THE AMERICAN CHEMICAL SOCIETY. III. PMID- 17748419 TI - Centennial of Discovery of Neanderthal Man. PMID- 17748420 TI - Centenary of J. J. Thomson. PMID- 17748421 TI - News of Science. PMID- 17748422 TI - News of Science. AB - On page 925 of the 9 Nov. issue of Science we stated that "Nineteen members of the Atomic Energy Commission research project at the University of Rochester Medical Center" endorsed a statement criticizing the President's recent defense of nuclear weapons tests. Actually, only five of the 19 members of the university staff who signed the statement were associated with the AEC project. These five constituted about 10 percent of the project's scientific staff. PMID- 17748424 TI - Permeable Spots in the Cuticle of the Thin-Walled Pegs on the Antenna of the Grasshopper. PMID- 17748423 TI - Does Starvation Increase Sperm Count? PMID- 17748425 TI - Effect of a Severe Storm on Electric Properties of a Tree and the Earth. PMID- 17748428 TI - Miscellaneous Publications. PMID- 17748426 TI - Rigidity of the Earth's Core. PMID- 17748429 TI - Meetings and Societies. PMID- 17748430 TI - EQUIPMENT NEWS. PMID- 17748431 TI - COMMENT AND CRITICISM. PMID- 17748433 TI - Fish remains in North-American Silurian rocks. PMID- 17748432 TI - Korean curios. PMID- 17748435 TI - A COMPARATIVE STUDY OF THE ASSOCIATIONS. PMID- 17748434 TI - Phosphorescence in the deep sea. PMID- 17748436 TI - THE CARSON-CITY ICHNOLITES. PMID- 17748437 TI - THE VIRULENCE OF CULTIVATED ANTHRAX VIRUS. PMID- 17748438 TI - EISSLER'S MODERN HIGH EXPLOSIVES. PMID- 17748439 TI - BRITISH ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17748440 TI - THE OHIO AGRICULTURAL EXPERIMENT STATION. PMID- 17748441 TI - Erratum. AB - In the report "Sequence of 16S ribosomal from Halobacterium volcanii, an archaebacterium" by R. Gupta et al. (12 August, p. 656), the last sentence of the abstract should read: "Since the H. volcanii sequence is closer to both the eubacterial and eukaryotic sequences than these two are to one another, it follows that the archaebacterial sequence is more like the common ancestral sequence than at least one of the other two versions." Also, the sentence beginning on line 6, column 3, page 658, should read: "Although the root of this tree cannot be determined, the data demand that the archaebacterial version be closer to the ancestral version common to all than are one or both of the other two versions." PMID- 17748442 TI - R-DNA. PMID- 17748443 TI - Language and science policies of new nations. PMID- 17748445 TI - Computer Break-Ins Fan Security Fears: But experts say computers containing classified material are invulnerable and that others can be made more secure. PMID- 17748444 TI - Thermoelectric energy conversion with solid electrolytes. AB - The alkali metal thermoelectric converter (AMTEC) is a device for the direct conversion of heat to electrical energy. The sodium ion conductor beta"- alumina is used to form a high-temperature regenerative concentration cell for elemental sodium. An AMTEC of mature design should have an efficiency of 20 to 40 percent, a power density of 0.5 kilowatt per kilogram or more, no moving parts, low maintenance requirements, high durability, and efficiency independent of size. It should be usable with high-temperature combustion, nuclear, or solar heat sources. Experiments have demonstrated the feasibility of the AMTEC and confirmed the theoretical analysis of the device. A wide range of applications from aerospace power to utility power plants appears possible. PMID- 17748446 TI - IOM Elects New Members. PMID- 17748448 TI - NSF Urged to Support Academic Supercomputing. PMID- 17748447 TI - Universities Denounce DOE's Secrecy Rules: They are joined by a broad array of critics in claiming that proposed regulations infringe academic freedom and citizens' rights. PMID- 17748449 TI - California universities block animal rights bill. PMID- 17748451 TI - Extinctions and the History of Life: Now that, for many at least, asteroid impact has been accepted as a causative agent in mass extinction, attention turns to the wider view. PMID- 17748450 TI - EPA planned to alter carter policy on cancer. PMID- 17748452 TI - A Visible Free Electron Laser in France: A string of firsts for an Orsay-Stanford collaboration: the first free electron laser in the visible, in a storage ring, and in Europe. PMID- 17748453 TI - Fading El Nino Broadening Scientists' View: El Nino and its attendant climatic extremes are weakening, leaving specialists looking even farther afield for ultimate causes. PMID- 17748454 TI - AAAS and Science on the Air. PMID- 17748455 TI - The dark side of science published. PMID- 17748457 TI - International activities in detroit. PMID- 17748459 TI - Geologic time: a geologic time scale. PMID- 17748456 TI - Nominees invited for scientific freedom and responsibility award. PMID- 17748458 TI - A call for help. PMID- 17748460 TI - A cultural chronology: ceramics, chronology, and community patterns. PMID- 17748461 TI - Recognition behavior: comparative social recognition. PMID- 17748463 TI - Single gene mutations in tomato plants regenerated from tissue culture. AB - Plants were regenerated from cultured leaf explants of an inbred variety of Lycopersicon esculentum. Seeds were collected from the regenerated plants and sown in the greenhouse. The resultant plants were then evaluated in the field. Several monogenic mutations segregated in the progeny of regenerated plants. The recovery of single gene mutations is evidence that plant tissue culture can be mutagenic. Complementation tests revealed that one mutation was located on the long arm of chromosome 10. PMID- 17748462 TI - The possible link between net surface heating and el nino. AB - Three diagnostic analyses are described which strongly suggest the importance of local net surface heating in the life history of the large-scale, air-sea phenomenon centered in the eastern tropical Pacific Ocean, commonly called El Nino. These analyses rely upon monthly marine weather summaries for the period 1957 to 1976. In the first, correlations and coherence spectra were calculated which show a strong link between the net surface heat flux and sea-surface temperature variations over the eastern equatorial Pacific. The second analysis, also based upon the use of coherence spectra, indicates a sea temperature precursor in the eastern ocean near 25 degrees S which precedes sea temperature changes near the El Nino focus near 5 degrees S. Since the link between the two regions would require ocean advective velocities that appear to be unreasonably large, this analysis also suggests the importance of atmospheric forcing through the surface heat flux. In the third analysis a proxy variable is described that seems to be a reasonable indicator of the overall effect of ocean dynamics on the temperature of the El Nino core region. A composite analysis of the four El Nino events of 1957, 1965, 1972, and 1976 suggests that local surface heating is important during the early part of an event, whereas dynamical factors dominate later. PMID- 17748464 TI - Optimization: a result or a mechanism? PMID- 17748465 TI - How Helpful Is Freedom? PMID- 17748466 TI - Information Theory: A brief survey is made of the recent developments and the current status of information theory. PMID- 17748467 TI - Science in the Courts: The Supreme Court Is Asked To Decide on the Inherent Dangers of Nuclear Reactors. PMID- 17748468 TI - Afferent Units in Dorsal Roots of Cat Driven by Respiration. AB - Single-fiber activity synchronous with breathing was recorded from the dorsal roots of thoracic segments in anesthetized cats. Activity of these fibers varied in frequency and in phase relationship to the respiratory cycle. It is concluded that large numbers of proprioceptors within the thoracic wall are activated during each inspiration and each expiration. PMID- 17748470 TI - Rare Tumor in Coast Redwood, Sequoia sempervirens. AB - A rare tumor on a conifer, Sequoia sempervirens, is described as it appears in situ and in section. Evidence is given which indicates, but does not prove, that the tumor had a developmental origin. PMID- 17748469 TI - Density of the Lunar Atmosphere. AB - The consequences of a model are worked out in which the lunar atmosphere is formed by gravitational accretion of interplanetary gas. Our results differ from those of Firsoff and of Brandt, partly because of the inapplicability of the barometric equation to the case of an exosphere. PMID- 17748471 TI - Phototropic Inversion in Phycomyces. AB - Transient reversed bending follows an adequate step-up in light intensity given a bending cell from any direction around its axis, yet the plane of the response is specifically that in which prior phototropic bending occurred. The cell "remembers" what it was doing and reverses this in the ensuing light-growth response. Antecedent asymmetric growth itself built the pattern for reversal. PMID- 17748472 TI - Nitrogen Deficiency and Fluoride Susceptibility of Bean Seedlings. AB - Groups of bean seedlings (Phaseolits vulgaris) were grown concurrently in cleaned and fluoride-containing (4 to 7 , microg of F(-) per cubic meter) air in plant growth chambers for 10 and 20 days with six water-culture treatments: Hoaglund's formulation and Hoaglund's minus potassium, calcium, nitrogen, phosphorus, and iron. An inadvertent 15-hour exposure on day 15 (at 42 microg/m(3)) produced foliar fluorosis symptoms only on the nitrogen-deficient plants fumigated 20 days, although higher fluoride concentrations were present in the foliage of similar plants grown in the other nutrient-deficient solutions. PMID- 17748473 TI - Recovery from Electroconvulsive Shock as a Function of Infantile Stimulation. AB - Eighty Wistar rats were handled at 2 to 5, 6 to 9, or 10 to 13 days of age, or not at all. In adulthood each group was split into halves with one-half of each group receiving electroconvulsive shock treatment. Assays of sugar concentration in the blood serum 24 hours after the convulsions indicated that subjects handled at 2 to 5 days of life exhibited no effect of the treatment, whereas all other groups showed marked increases in blood sugar concentration. PMID- 17748474 TI - The Third Denver Meeting: Some Background. PMID- 17748476 TI - THE MOUSE PLAGUE IN CALIFORNIA. PMID- 17748475 TI - Forthcoming Events. PMID- 17748477 TI - "EXCITED" ATOMS. PMID- 17748478 TI - PSYCHOLOGY APPLIED TO THE AIR SERVICE. PMID- 17748480 TI - MICROSCOPIC PHYSIOLOGY. PMID- 17748479 TI - ORION IN THE SOUTHERN SKY. PMID- 17748481 TI - PROTECTION OF THE TEXAS LONGHORN. PMID- 17748482 TI - INFRA-RED SPECTROSCOPY. PMID- 17748483 TI - SCIENTIFIC SERVICE THAT THE NATIONAL FORESTS MIGHT BE RENDERING. PMID- 17748484 TI - THE AWARD OF THE FIRST CHARLES REID BARNES LIFE MEMBERSHIP OF THE AMERICAN SOCIETY OF PLANT PHYSIOLOGISTS. PMID- 17748485 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17748487 TI - BABYLONIAN DISCOVERY OF THE PRECESSION OF THE EQUINOXES. PMID- 17748486 TI - PUBLICATION BY PHOTOGRAPHY. PMID- 17748488 TI - METAPSYCHICS. PMID- 17748489 TI - EXPLORATION OF THE ETOWAH MOUNDS. PMID- 17748490 TI - A SIMPLE LABORATORY QUARTZ MERCURY LAMP. PMID- 17748491 TI - SAP FLOW AND PRESSURE IN TREES. PMID- 17748492 TI - THE RISE OF NATURAL HISTORY MUSEUMS. PMID- 17748493 TI - THE BACTERIA OF THE INTESTINAL TRACT OF MAN. PMID- 17748494 TI - PROTECTION OF BIRDS IN THE MALAY PENINSULA. PMID- 17748495 TI - REVERCHON PARK, DALLAS, TEXAS. PMID- 17748496 TI - BRITISH SCIENTIFIC MEN IN MILITARY SERVICE. PMID- 17748497 TI - THE AMERICAN CHEMICAL SOCIETY. PMID- 17748498 TI - CANCER AND HEREDITY. PMID- 17748499 TI - SUGAR-BEET MOSAIC. PMID- 17748502 TI - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (NUMBER 7). PMID- 17748500 TI - RADIUM FERTILIZER. PMID- 17748501 TI - DELPHINUS AND PHOCAeNA IN THE DELAWARE. PMID- 17748504 TI - SCIENCE NEWS. PMID- 17748503 TI - ON HYDRATION AND "SOLUTION" IN GELATIN. PMID- 17748506 TI - THE INVOLVED GENETICS OF FISH. PMID- 17748505 TI - SOLAR ECLIPSE PROBLEMS. PMID- 17748507 TI - ZOOLOGICAL NOMENCLATURE. PMID- 17748508 TI - NOTE ON THE LIFE-CYCLE OF ECTOCARPUS SILICULOSUS DILLW. PMID- 17748509 TI - ON THE SCIENTIFIC NAME OF THE WEBBING CLOTHES MOTH. PMID- 17748510 TI - HUMAN NECROBACILLOSIS. PMID- 17748511 TI - A METHOD AND THE APPARATUS FOR THE STUDY OF PERMEABILITY OF GASES THROUGH THE BIRD'S EGGSHELL. PMID- 17748513 TI - A METHOD FOR THE PREPARATION OF FOSSILS. PMID- 17748512 TI - THE UTILIZATION OF ADSORBED IONS BY PLANTS. PMID- 17748514 TI - OBSERVATIONS ON EARLY DEVELOPMENTAL PROCESSES IN THE LIVING EGG OF DROSOPHILA. PMID- 17748515 TI - Letters to the editor. PMID- 17748516 TI - Letters to the editor. PMID- 17748517 TI - Letters to the editor. PMID- 17748518 TI - Enigmas of violence. PMID- 17748519 TI - What to expect. PMID- 17748520 TI - Slippery water in fire hoses. PMID- 17748521 TI - Objectivity in the courts. PMID- 17748522 TI - A tribute to frederick seitz. PMID- 17748523 TI - New detectors for high-energy physics. PMID- 17748524 TI - Polywater. PMID- 17748526 TI - Atoms for peace awards. PMID- 17748525 TI - Analysis of restricted neural networks. PMID- 17748527 TI - McElroy Proposed To Head NSF; Branscomb, Bureau of Standards. PMID- 17748528 TI - Generation of an artificial aurora. AB - On 26 January 1969 an Aerobee 350 rocket was fired from Wallops Island, Virginia, carrying an electron accelerator. Above 230 kilometers the electron guns put out a beam of 0.5 ampere of 10 kev electrons in pulses of 1-second duration aimed downward along the earth's magnetic field lines. The interaction of electron beam with the atmosphere at an altitude of about 100 kilometers generated enough light so that the auroral rays produced could be photographed on the ground by television camera systems. PMID- 17748529 TI - Waterfall-generated Earth vibrations. AB - Waterfalls generate periodic earth vibrations whose frequencies are inversely proportional to the height of the waterfall. Action of turbulent eddies is a probable explanation. PMID- 17748530 TI - Lunar surface material: spacecraft measurements of density and strength. AB - The relation of the density of the lunar surface layer to depth is probably best determined from spacecraft measurements of the bearing capacity as a function of depth. A comparison of these values with laboratory measurements of the bearing capacity of low-cohesion particulate materials as a function of the percentage of solid indicates that the bulk density at the lunar surface is about 1.1 grams per cubic centimeter and that it increases nearly linearly to about 1.6 grams per cubic centimeter at a depth of 5 centimeters. PMID- 17748531 TI - Fission track age of magnetic anomaly 10: a new point on the sea-floor spreading curve. AB - A portion of basaltic glass retrieved from an abyssal hill in the northeast Pacific has been dated by the fission track method. The sample location corresponds to magnetic anomaly 10 believed to have resulted from sea-floor spreading. The age of this sample is 35 +/- 5 million years, which is in agreement with the previously proposed age of 31 to 32 million years based on linear extrapolation of measured recent spreading rates. This observation upholds the suggestions of other authors on the time variation of sea-floor spreading for the last 30 million years in various parts of the world ocean basin. PMID- 17748532 TI - Permian insect wing from antarctic sentinel mountains. AB - A homopterous insect wing was found in micaceous graywacke from the Polarstar Formation, Sentinel Mountains. The unusual venation is reminiscent of family Stenoviciidae known from the Permian and Triassic of Eastern Australia and elsewhere. This first documented account of Paleozoic insects in Antarctica bears on drift questions. PMID- 17748533 TI - The attraction of minicomputers. PMID- 17748534 TI - Technical issues and the adversary process. PMID- 17748535 TI - Peer review:preventing "nepotism". PMID- 17748536 TI - Dating the deluge. PMID- 17748538 TI - Unesco's Tarnished Image. PMID- 17748537 TI - A neglected literature. PMID- 17748539 TI - Explosive cenozoic volcanism and climatic implications. PMID- 17748540 TI - IQ and Heredity: Suspicion of Fraud Beclouds Classic Experiment. PMID- 17748541 TI - Superport for palau debated: ecopolitics in the far pacific. PMID- 17748543 TI - State scientffic advisers: the effort in michigan. PMID- 17748542 TI - Birth control: report argues new leads are neglected. PMID- 17748544 TI - Viking (II): Water, Ice, and Argon--Three Puzzles Resolved. PMID- 17748545 TI - Irrational drug prescribing and birth defects. PMID- 17748546 TI - The 1976 nobel prize for physiology or medicine. PMID- 17748547 TI - Windows on other minds. PMID- 17748548 TI - The science of values. PMID- 17748549 TI - Biomechanics. PMID- 17748550 TI - Giraffa camelopardalis. PMID- 17748551 TI - Dependability of wind energy generators with short-term energy storage. AB - Power fluctuations and power duration curves for wind energy generators, including energy storage facilities of a certain capacity, are compared to those of typical nuclear reactors. A storage system capable of delivering the yearly average power output for about 10 hours already makes the dependability of the wind energy system comparable to that of a typical nuclear plant. PMID- 17748552 TI - New Rules for AAAS-Newcomb Cleveland Prize. PMID- 17748553 TI - Calcium carbonate production, coral reef growth, and sea level change. AB - Shallow, seaward portions of modern coral reefs produce about 4 kilograms of calcium carbonate per square meter per year, and protected areas produce about 0.8 kilogram per square meter per year. The difference is probably largely a function of water motion. The more rapid rate, equivalent to a maximum vertical accretion of 3 to 5 millimeters per year, places an upper limit on the potential of modern coral reef communities to create a significant vertical structure on a rising sea. PMID- 17748554 TI - Ultragiant urban aerosol particles. AB - Measurements taken 300 meters above ground level show surprisingly high concentrations of ultragiant aerosol particles both upwind and downwind of the St. Louis, Missouri, urban area. Assuming an average particle density of 2.0 grams per cubic centimeter, concentrations of particles with diameters between 5 and 55 micrometers sampled on 11 different days averaged 31 micrograms per cubic meter upwind and 55 micrograms per cubic meter downwind of the city. PMID- 17748555 TI - Short-period climatic fluctuations: effects on diatom biomass. AB - An analysis of the weekly averages of diatom biomass measured near the coast of Southern California (32 degrees 50'N, 117 degrees 10'W) during the period from 1928 through 1939 indicates that three major blooms account for 85 percent of each year's diatom biomass. The average duration of a single bloom is 5.5 weeks. The diatom blooms coincide with upwelling, but their individual characteristics depend on the detailed features of the circulation patterns of the water masses. That is, if upwelling takes place after a large influx of subtropical or even tropical water because of the slackening California Current, the resulting diatom blooms are smaller by several orders of magnitude than those observed when the flow of the current is strong. This influx of subtropical water into the region is reflected in positive anomalies of temperature, salinity, and sea level. PMID- 17748556 TI - Cellulosic microfibrils: nascent stages of synthesis in a higher plant cell. AB - Freeze-fracturing of untreated plasma membrane and inner wall surfaces of stelar tissue in corn roots demonstrated the association of globular complexes with the ends of nascent microfibrils. It is proposed that the granule complexes associated with the outer leaflet of the plasma membrane coordinate the assembly of the cellulosic microfibrils. PMID- 17748557 TI - THE SOCIETY OF AMERICAN NATURALISTS. MEETING OF THE CENTRAL BRANCH. PMID- 17748558 TI - SOME ASPECTS OF THE ENDOWMENT OF RESEARCH. PMID- 17748560 TI - AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. SECTION E--GEOLOGY AND GEOGRAPHY. PMID- 17748559 TI - ADDRESS OF WELCOME BY PRESIDENT ANGELL. PMID- 17748561 TI - MORPHOLOGY AND PHYLOGENY. PMID- 17748562 TI - THE AFFILIATION OF PSYCHOLOGY WITH PHILOSOPHY AND WITH THE NATURAL SCIENCES. PMID- 17748563 TI - ECOLOGICAL ADAPTATION AND ECOLOGICAL SELECTION. PMID- 17748564 TI - 'BARRIERS' AND 'BIONOMIC BARRIERS' OR ISOLATION AND NON-ISOLATION AS BIONOMIC FACTORS. PMID- 17748565 TI - ON THE BREAKING-UP OF THE OLD GENUS CULEX. PMID- 17748566 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17748567 TI - IMPORTATIONS OF THE PRICKLY PEAR FROM MEXICO. PMID- 17748568 TI - THE CONGRESS OF THE UNITED STATES. PMID- 17748569 TI - THE COMING MEETING OF THE MUSEUMS ASSOCIATION OF AMERICA. PMID- 17748570 TI - ADDRESS TO THE ENGINEERING SECTION OF THE BRITISH ASSOCIATION. PMID- 17748571 TI - IN MEMORY OF JOHN WESLEY POWELL. PMID- 17748572 TI - THE CARNEGIE INTSTITUTION. PMID- 17748573 TI - AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. SECTION D, ANTHROPOLOGY. PMID- 17748574 TI - EXCEPTIONS TO MENDEL'S LAW. PMID- 17748576 TI - THE COMET B, 1902, AND THE MASS OF MERCURY. PMID- 17748575 TI - NOTES ON INORGANIC CHEMISTRY. PMID- 17748577 TI - SCIENCE NEWS. PMID- 17748578 TI - PHOTONS IN CHEMISTRY AND BIOLOGY. PMID- 17748579 TI - STUDIES OF CRYSTALLINE VITAMIN B1 VII. ITS RELATION TO PATHOLOGICAL STATES. PMID- 17748580 TI - A KITCHEN MIDDENS WITH BONES OF EXTINCT ANIMALS IN THE UPPER LAKES AREA. PMID- 17748581 TI - THE APPLICATION OF ARTIFICIALLY IONIZED AIR. PMID- 17748582 TI - A PHYTOSTEROL AND PHYTOSTEROLIN FROM THE SWEET POTATO. PMID- 17748584 TI - EXPERIMENTAL ADAPTATION OF FRESHWATER CILIATES TO SEA WATER. PMID- 17748583 TI - DISTRIBUTION OF SEPARATES OF CERTAIN PAPERS BY THE LATE DR. BASHFORD DEAN. PMID- 17748585 TI - NEW ARRANGEMENT FOR REGULATING FLOW OF LIQUID INTO A CULTURE VESSEL. PMID- 17748587 TI - A GENE FOR CONTROL OF INTERSTITIAL LOCALIZATION OF CHIASMATA IN ALLIUM FISTULOSUM L. PMID- 17748586 TI - A SECOND-GENERATION CAPTIVE-BORN CHIMPANZEE. PMID- 17748588 TI - HOW LONG DO ROOTS OF GRASSES LIVE? PMID- 17748589 TI - INTRODUCTORY REMARKS BY THE PRESIDENT OF THE ACADEMY. PMID- 17748590 TI - PRESENTATION OF THE PUBLIC WELFARE MEDAL TO DR. HUGH SMITH CUMMING. PMID- 17748591 TI - RESPONSE OF THE MEDALLIST. PMID- 17748593 TI - RESPONSE ON BEHALF OF THE MEDALLIST. PMID- 17748592 TI - PRESENTATION OF THE JOHN J. CARTY MEDAL AND AWARD TO DR. EDMUND BEECHER WILSON. PMID- 17748594 TI - SIGNIFICANT FIGURES IN STATISTICAL CONSTANTS. PMID- 17748595 TI - LENGTH OF LIFE OF A RABBIT. PMID- 17748596 TI - HYDROGEN AND CARBON DIOXIDE PHOTO-ASSIMILATION IN PURPLE BACTERIA. PMID- 17748597 TI - THE SIZE OF THE UNIVERSE AND THE FUNDAMENTAL CONSTANTS OF PHYSICS. PMID- 17748598 TI - TYPE SPECIFIC ANTIPNEUMOCOCCUS RABBIT SERUM. PMID- 17748600 TI - IDENTICAL TWINS IN A MOUSE CROSS. PMID- 17748601 TI - A METHOD OF DEMONSTRATING CO, PRODUCTION DURING RESPIRATION. PMID- 17748599 TI - A NEW APPARATUS FOR CONSTANT TEMPERATURE. PMID- 17748603 TI - THE SECOND INTERNATIONAL CONVENTION OF THE INTERNATIONAL CATALOUGE OF SCIENTIFIC LITERATURE, LONDON, 1910. PMID- 17748602 TI - THE VISUALIZATION OF DIFFERENT ORGANS IN NORMAL UNANESTHETIZED ANIMALS. PMID- 17748604 TI - SOME PRUSSIAN EDUCATIONAL DATA. PMID- 17748605 TI - EDWIN E. HOWELL. PMID- 17748606 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17748607 TI - HERMAN KNAPP. PMID- 17748609 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17748608 TI - PHARMACOLOGICAL ACTION OF THE NON-ALCOHOLIC CONSTITUENTS OF ALCOHOLIC BEVERAGES. PMID- 17748610 TI - THE APPOINTMENT, PROMOTION AND REMOVAL OF OFFICERS OF INSTRUCTION. PMID- 17748611 TI - NOTES ON METEOROLOGY AND CLIMATOLOGY. PMID- 17748612 TI - THE SOIL, A LIVING THING. PMID- 17748614 TI - A POSSIBLE LINE OF DESCENT OF THE GOBIOID FISHES. PMID- 17748613 TI - OOSPORES OF POTATO BLIGHT. PMID- 17748615 TI - CARCHARIAS BORNEENSIS AND BARBUS ELONGATUS, AS PREOCCUPIED NAMES. PMID- 17748617 TI - A Theory of Ice Ages. PMID- 17748616 TI - Test by Testimonial. PMID- 17748618 TI - News of Science. PMID- 17748620 TI - Effect of Polarized Light on Polarity of Fucus. PMID- 17748619 TI - Nature of Protein Synthesis in Sweetpotato Infected with Ceratostomella fimbriata. PMID- 17748622 TI - Scientific Meetings. PMID- 17748623 TI - SCIENCE NEWS. PMID- 17748624 TI - ADDRESS OF THE PRESIDENT. PMID- 17748625 TI - PRESENTATION OF THE MARY CLARK THOMPSON MEDAL. PMID- 17748626 TI - VARIATION AND EVOLUTION AMONG THE STARS. PMID- 17748627 TI - BALANCED DIETS, NET ENERGY VALUES AND SPECIFIC DYNAMIC EFFECTS. PMID- 17748628 TI - ITALIAN WORK ON LIVER THERAPY. PMID- 17748629 TI - A COLOR TEST FOR VITAMIN C. PMID- 17748630 TI - A DEVICE FOR WATER CIRCULATION. PMID- 17748631 TI - IMPROVEMENT OF PARAFFIN SECTIONS BY IMMERSION OF EMBEDDED TISSUES IN WATER. PMID- 17748632 TI - MONOCYTES AS AN INDICATOR OF CERTAIN STATES OF BLOOD SERUM. PMID- 17748633 TI - TEMPORARY PREVENTION BY CHEMICAL MEANS OF INTRANASAL INFECTION OF MICE WITH EQUINE ENCEPHALOMYELITIS VIRUS. PMID- 17748634 TI - X-RAY DIFFRACTION STUDIES, ON NERVE. PMID- 17748635 TI - Letters to the editor. PMID- 17748636 TI - Letters to the editor. PMID- 17748637 TI - Letters to the editor. PMID- 17748638 TI - Women academics. PMID- 17748639 TI - The cable car. PMID- 17748640 TI - Letters to the editor. PMID- 17748641 TI - Sorensen and pH. PMID- 17748642 TI - Testing for teratogenicity. PMID- 17748643 TI - Cooperation. PMID- 17748644 TI - Intertwined societal problems. PMID- 17748645 TI - The upper atmosphere observatory. PMID- 17748647 TI - Kennedy Asks NSF Budget Boost. PMID- 17748646 TI - Nuclear Reactor Safety: At the AEC the Way of the Dissenter Is Hard. PMID- 17748648 TI - Sierra club foiled in high court. PMID- 17748649 TI - Doom spelled for vampires. PMID- 17748650 TI - APS Challenged on Bulletin Censorship, Charter Changes, by Activists Concerned about War, Physicists' Role. PMID- 17748651 TI - NAS: Academy Votes NRC Changes, New Formula on Classified Research. PMID- 17748652 TI - Heat flow and convection demonstration experiments aboard apollo 14. AB - A group of experiments was conducted by Apollo 14 astronaut Stuart A. Roosa during the lunar flyback on 7 Fehruary 1971 to obtain information on heat flow and convection in gases and liquids in an environment of less than 10-(6)g gravity. Flow observations and thermal data have shown that: (i) there are, as expected, convective motions caused by surface tension gradients in a plane liquid layer with a free upper surface; (ii) heat flow in enclosed liquids and gases occurs mainly by diffusive heat conduction; and (iii) some convective processes, whose characteristics are not fully known, add to the heat transfer. PMID- 17748653 TI - Helical filaments produced by a Mycoplasma-like organism associated with corn stunt disease. AB - Mycoplasma-like bodies with helical filaments were seen by phase contrast microscopy in juice expressed from tissues of plants infected with corn stunt agent. Each filament is bounded by a "unit membrane" and no cell wall, sheath, envelope, or second membrane has yet been discerned by electron microscopy. The association of these filaments with development of disease, their occurrence in phloem cells as seen by both freeze-etching and thin-section electron microscopy, the diagnosis of infection based on their presence in plants without symptoms, and their absence in noninfected corn are consistent with the hypothesis that these unusual filaments are formed by the mycoplasma-like organism presumed to be the corn stunt agent. PMID- 17748654 TI - Information-processing by pigeons. AB - Two pigeons matched to sample on the basis of color or line orientation when a sample consisted of a value for each stimulus dimension or a value for only one dimension. When the duration of the sample stimulus was varied to maintain constant performance, compound stimuli required more time than single elements. PMID- 17748655 TI - Relative Consumer Species Diversity with-Respect to Producer Diversity and Net Productivity. PMID- 17748656 TI - Energy in the soviet union. PMID- 17748657 TI - Details of the DeFunis Case. PMID- 17748658 TI - Solar energy development. PMID- 17748659 TI - Breast cancer and chemotherapy. PMID- 17748661 TI - Detente in space. PMID- 17748660 TI - Turning out the vote. PMID- 17748662 TI - National institute on aging: new focus on growing old. AB - Though the leaves are many, the root is one; / Through all the lying days of my youth / I swayed my leaves and flowers in the sun; / Now I may wither into the truth.-W. B. YEATS, "The Coming of Wisdom with Time" PMID- 17748663 TI - For aging research the best is yet to be. PMID- 17748664 TI - Senate acts on pathology institute. PMID- 17748665 TI - FDA: Review Panel Faults Commissioner's Defense of Agency. PMID- 17748667 TI - The rise and fall of a research project. PMID- 17748666 TI - Interior releases new standards for surface mining. PMID- 17748668 TI - Congress buys small is beautiful. PMID- 17748670 TI - Patents: Federal Employee's Suit Opposes "Rip-Off" by Government. PMID- 17748669 TI - Ford signs science policy bill. PMID- 17748671 TI - Autoimmune disease: new evidence about lupus. PMID- 17748672 TI - The development of the chemical arts. PMID- 17748673 TI - Primate studies. PMID- 17748674 TI - Marine chemistry. PMID- 17748675 TI - Plates of the dinosaur stegosaurus: forced convection heat loss fins? AB - It is suggested that the plates along the arched back and tail of Stegosaurus served an important thermoregulatory function as forced convection "fins." Wind tunnel experiments on finned models, internal heat conduction calculations, and direct observations of the morphology and internal structure of stegosaur plates support this hypothesis, demonstrating the comparative effectiveness of the plates as heat dissipaters, controllable through input blood flow rate, temperature, and body orientation (with respect to wind). PMID- 17748676 TI - Electrical energy storage and intercalation chemistry. AB - The electrochemical reaction of layered titanium disulfide with lithium giving the intercalation compound lithium titanium disulfide is the basis of a new battery system. This reaction occurs very rapidly and in a highly reversible manner at ambient temperatures as a result of structural retention. Titanium disulfide is one of a new generation of solid cathode materials. PMID- 17748677 TI - Masses of the galilean satellites of jupiter. AB - Numerical data derived from the observation of the four great satellites of Jupiter are compared with the values obtained through Sampson's theory by using the new JPL (Jet Propulsion Laboratory) system of masses. It is not possible to fit the coefficient of the free oscillation in the longitude of Ganymede, whose argument is l(3) - omega(4) (the mean longitude of Ganymede referred to the proper apse of Callisto), and the mass of Callisto derived from the path of Pioneer 10. PMID- 17748678 TI - Methylation of selenium in the aquatic environment. AB - Conversion of inorganic and organic selenium compounds to volatile selenium compounds (dimethyl selenide, dimethyl disetenide, and an unknown compound) by microorganisms in lake sediment has been observed. This conversion could also be effected by pure cultures of bacteria and fungi. Such transformations are significant in the transportation and cycling of elements in the environment. PMID- 17748680 TI - PRODUCTS and MATERIALS. PMID- 17748679 TI - Fossilized eggs in a pennsylvanian blastoid. AB - A single specimen of Pentremites rusticus (Echinodermata, Blastoidea) from the Early Pennsylvanian of Oklahoma has hundreds of apparent eggs in one of its abnormal anal hydrospire groups. This rare occurrence suggests that female blastoids in this sexually dimorphic species had modified their anal hydrospiresfor brooding eggs instead of for normal respiration. PMID- 17748681 TI - This week in science. PMID- 17748683 TI - In Reply: NASA and University Astronomers. PMID- 17748682 TI - Government and quality in science. PMID- 17748684 TI - NASA and University Astronomers. PMID- 17748686 TI - Superconductivity applications. PMID- 17748685 TI - The "misplaced" fossils. PMID- 17748688 TI - Erratum. AB - The caption for figure 1 (p. 1497) of the report "Transformation by v-sis occurs by an internal autoactivation mechanism" by B. E. Bejcek et al. (29 Sept., p. 1496) was inadvertently not printed. The caption should have read, "Fig. 1. (A) Plasmid pSEB3 (B) Mutations used." PMID- 17748689 TI - Early man site visits. PMID- 17748690 TI - Congress finds bugs in the software. PMID- 17748691 TI - Good news for superconductors. PMID- 17748693 TI - How to build a synapse. PMID- 17748692 TI - A temporary scaffolding helps build brains. PMID- 17748694 TI - A Wizard of Middle Earth Under Fire: For 10 years Raymond Jeanloz has been shaking up mineral physics; now he is facing some major tests himself. PMID- 17748695 TI - Recipe for a bit of deep Earth. PMID- 17748696 TI - Faith in fifth force fades. PMID- 17748697 TI - Sellers' market for scarce chemists. PMID- 17748698 TI - Neuroscience crsis at washington u.? PMID- 17748699 TI - Physics budget squeeze ahead at energy. PMID- 17748700 TI - How color affects people and work. PMID- 17748701 TI - Canadian sciences net $240 million. PMID- 17748702 TI - Dispelling myths about verification of sea-launched cruise missiles. AB - It is widely believed that an arms control limit on nuclear-armed sea-launched cruise missiles would be nearly impossible to verify. Among the reasons usually given are: these weapons are small, built in nondistinctive industrial facilities, deployed on a variety of ships and submarines, and difficult to distinguish from their conventionally armed counterparts. In this article, it is argued that the covert production and deployment of nuclear-armed sealaunched cruise missiles would not be so straightforward. A specific arms control proposal is described, namely a total ban on nuclear-armed sea-launched cruise missiles. This proposal is used to illustrate how an effective verification scheme might be constructed. PMID- 17748703 TI - Photoemission spectroscopy of the high-temperature superconductivity gap. AB - Superconductivity is related to the presence of a narrow forbidden gap in the spectrum of the possible energies for the electrons in the material. These "superconductivity gaps" have traditionally been studied with tunneling and infrared absorption experiments. A third, powerful technique has been made possible by the discovery of hightransition temperature materials: the direct observation of the gap in photoemission spectra. The data analysis requires a careful reconsideration of the standard Einstein-Fermi model of the photoelectric effect. The conclusions are surprisingly simple and offer an alternate way to measure superconductivity gaps. This approach can also be used to study the directional properties of the gap, phenomena related to the coherence length, and possible departures from Fermi-liquid behavior. PMID- 17748704 TI - Effects of the Large June 1975 Meteoroid Storm on Earth's Ionosphere. AB - The June 1975 meteoroid storm detected on the moon by the Apollo seismometers was the largest ever observed. Reexamination of radio data taken at that time showed that the storm also produced pronounced disturbances on Earth, which were recorded as unique phase anomalies on very low frequency (VLF) radio propagation paths in the low terrestrial ionosphere. Persistent effects were observed for the major storm period (20 to 30 June 1975), including reductions in the diurnal phase variation, advances in the nighttime and daytime phase levels, and reductions in the sunset phase delay rate. Large nighttime phase advances, lasting a few hours, were detected on some days at all VLF transmissions, and for the shorter propagation path they were comparable to solar Lyman alpha daytime ionization. Ion production rates attributable to the meteor storm were estimated to be about 0.6 to 3.0 ions per centimeter cubed per second at the E and D regions, respectively. The storm was a sporadic one with a radiant (that is, the point of apparent origin in the sky) located in the Southern Hemisphere, with a right ascension 1 to 2 hours larger than the sun's right ascension. PMID- 17748705 TI - Phyllosilicate absorption features in main-belt and outer-belt asteroid reflectance spectra. AB - Absorption features having depths up to 5% are identified in high-quality, high resolution reflectance spectra of 16 dark asteroids in the main belt and in the Cybele and Hilda groups. Analogs among the CM2 carbonaceous chondrite meteorites exist for some of these asteroids, suggesting that these absorptions are due to iron oxides in phyllosilicates formed on the asteroidal surfaces by aqueous alteration processes. Spectra of ten additional asteroids, located beyond the outer edge of the main belt, show no discernible absorption features, suggesting that aqueous alteration did not always operate at these heliocentric distances. PMID- 17748706 TI - Analysis of the published calorimetric evidence for electrochemical fusion of deuterium in palladium. AB - Estimates are given of the raw data that are the basis for the claims of excess power production by the electrochemical charging of palladium in deuterium oxide (D(2)O). Calorimetric results are also presented that show no anomalous power production in either 0.1M LiOD/D(2)O or 0.1M LiOH/H(2)O (LiOH is lithium hydroxide). Several possible sources of error in open-system calorimetry are discussed that can confound interpretation of temperature changes in terms of anomalous power production. PMID- 17748708 TI - In Reply: PCR Analysis of DNA from Multiple Sclerosis Patients for the Presence of HTLV-I. PMID- 17748707 TI - Dynamic pore-pressure fluctuations in rapidly shearing granular materials. AB - Results from two types of experiments show that intergranular pore pressures fluctuated dynamically during rapid, steady shear deformation of water-saturated granular materials. During some fluctuations, the pore water locally supported all normal and shear stresses, while grain-contact stresses transiently fell to zero. Fluctuations also propagated outward from the shear zone; this process modifies grain-contact stresses in adjacent areas and potentially instigates shear-zone growth. PMID- 17748709 TI - New Homeless and Old. Community and the Skid Row Hotel. Charles Hoch and Robert A. Slayton. Temple University Press, Philadelphia, 1989. x, 299 pp., illus., + plates. $32.95. Conflicts in Urban and Regional Development. PMID- 17748711 TI - From Neuropsychology to Mental Structure. Tim Shallice. Cambridge University Press, New York, 1988. xvi, 462 pp., illus. $59.50; paper, $24.95. PMID- 17748710 TI - Atoms for Peace and War, 1953-1961. Eisenhower and the Atomic Energy Commission (A History of the United States Atomic Energy Commission, vol. 3.) Richard G. Hewlett and Jack M. Holl. University of California Press, Berkeley, 1989. xxx, 696 pp. $60. California Studies in the History of Science, vol. 4. PMID- 17748712 TI - The Tropical Rain Forest. A First Encounter. Marius Jacobs. Remke Kruk et al., Eds., with a chapter by Roelof A. A. Oldeman. Springer-Verlag, New York, 1988. xiv, 295 pp., illus. Paper, $39.95. Translated, with revisions, from the Dutch edition (Muiderberg, 1981). PMID- 17748713 TI - Cantor's Dilemma. Carl Djerassi. Doubleday, New York, 1989. viii, 230 pp. $18.95. PMID- 17748714 TI - Products & materials. PMID- 17748715 TI - This week in science. PMID- 17748716 TI - In reply: young scientists and the future. PMID- 17748717 TI - Retraining the cranes. PMID- 17748718 TI - Chronic leaks plague shuttle science. PMID- 17748720 TI - Out of china...And now back in. PMID- 17748721 TI - Proton Microbeam Probes the Elements: A remarkable new instrument devised at Oxford University can magnify a specimen and analyze its elemental composition at the same time. PMID- 17748719 TI - Feds hush up a bum bomb detector. PMID- 17748723 TI - Millimeter Astronomers Push for New Telescope: The new facility would give them an unprecedented ability to study star and galaxy formation--but at a cost of $120 million. PMID- 17748722 TI - Signs of the parkfield quake? PMID- 17748724 TI - Magnetic confinement fusion. AB - Fusion plasmas with reactorlike temperatures have been confined in magnetic-field configurations of the tokamak type. The measured rate of heat leakage from these plasmas is sufficiently small to be compatible with the requirements of a full sized fusion power reactor. Improvements in other aspects of reactor performance are still needed, however, and the high cost of reactor- development steps has become an obstacle on the path to practical fusion power. PMID- 17748725 TI - Epitaxial and Smooth Films of a-Axis YBa2Cu3O7. AB - YBa(2)Cu(3)O(7) films have been grown epitaxially on SrTiO(3) (100) and LaAlO(3) (100) substrates with nearly pure a-axis orientation and with transition temperature T(c) (R = 0) of 85 K. A unique feature of these films is their smooth surface. These smooth surfaces enable the growth of short-period superlattices with well-defined modulations. The films are untwinned and the grains grow with their c-axis along one of two perpendicular directions on the substrate ([100] or [010]). The fabrication of sandwich-type Josephson junctions with good characteristics may now be possible because unlike c-axis-oriented films, the superconducting coherence length of these smooth films is appreciably large perpendicular to their surfaces. PMID- 17748726 TI - Cloth and Human Experience. Annette B. Weiner and Jane Schneider, Eds. Smithsonian Institution Press, Washington, DC, 1989. xvi, 431 pp., illus. $39.95. Smithsonian Series in Ethnographic Inquiry. Based on a conference, Troutbeck, NY, 1983. PMID- 17748727 TI - The Houshold Economy. Reconsidering the Domestic Mode of Production. Richard R. Wilk, Ed. Westview, Boulder, CO, 1989. viii, 266 pp. Paper, $36.95. PMID- 17748729 TI - Products & materials. PMID- 17748728 TI - The Moon Illusion. Maurice Hershenson, Ed. Erlbaum, Hillsdale, NJ, 1989. xvi, 421 pp., illus. $69.95. PMID- 17748731 TI - BIOGRAPHICAL NOTES ON LOUIS PASTEUR. PMID- 17748730 TI - CHARLES VALENTINE RILEY. PMID- 17748732 TI - HOLBROOK CUSHMAN. PMID- 17748733 TI - MEASUREMENTS OF THE ACCURACY OF RECOLLECTION. PMID- 17748734 TI - CURRENT NOTES ON ANTHROPOLOGY (XIV.). PMID- 17748735 TI - CURRENT NOTES ON PHYSIOGRAPHY (XX.). PMID- 17748736 TI - TESTIMONY VERSUS EVIDENCE. PMID- 17748737 TI - THE FEAR OF LIGHTNING. PMID- 17748739 TI - APPARATUS FOR THE ELECTRICAL MEASUREMENT OF ALTITUDE. PMID- 17748738 TI - BROOKS'S COMET. PMID- 17748741 TI - A TEST OF SOCIAL INTELLIGENCE. PMID- 17748740 TI - A NEW SOURCE OF HELIUM. PMID- 17748742 TI - THE WESTERN BOLL WEEVIL. PMID- 17748744 TI - SUPERFICIAL FACTORS IN EARTHQUAKES. PMID- 17748743 TI - THE ROLE OF EPITHELIUM IN EXPERIMENTAL IMMUNIZATION. AB - When a small amount of blood serum is dropped into the nose of a guinea pig the serum is absorbed by the mucous membrane and, after a definite period of incubation, the animal can be shown to have become profoundly changed. Depending upon the number of instillations, the interval between them and, especially, the quantity of serum instilled, the animal becomes either highly hypersensitive or strongly resistant to a toxic injection given by the vein. This resistance withstands a considerable series of increasing toxic injections and is strengthened with lapse of time,-contrary to the state of tolerance produced by traumatic methods. It is inferred that the absorption of foreign protein by the nose causes the formation of two different antibodies. One of these is allergic and excites to anaphylaxis; the other is protective and leads to true immuuity. The relative amount of either antibody can be regulated by modifying the amount of serum instilled. Added to a state of general allergy it is easy to produce, in the guinea pig, a special sensitization of the respiratory apparatus which leads, under appropriate stimulation, to attacks resembling those of bronchial asthma in man. No conclusion can be drawn at present concerning the nature or mode of action of the protective or immunizing antibody; but the indications are that its relations to the circulation and to tissue fixation resemble those which have been developed by other investigators in regard to the anaphylactic antibody. Evidence has been submitted that the living epithelium mediates between foreign protein and the organism in a way to favor specifically the elaboration of true immunity. PMID- 17748746 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17748745 TI - ALLAN RIVERSTON MCCULLOCH. PMID- 17748747 TI - SOLAR VARIATION AND THE WEATHER. PMID- 17748749 TI - AN OBVIOUS NEW CASE OF POLYEMBRYONY. PMID- 17748748 TI - THE "HARMLESS" CORAL SNAKE. PMID- 17748750 TI - TERTIARY GLACIATION IN WYOMING, COLORADO AND UTAH. PMID- 17748751 TI - AN INEXPENSIVE AIR PRESSURE INJECTION APPARATUS. PMID- 17748752 TI - CERTAIN OXIDES OF IRON IN SOME NEW CATALYTIC ACTIONS. PMID- 17748753 TI - Fare Enough. PMID- 17748755 TI - News of Science: Excerpts from the Summary and Conclusions of the Report of the United Nations Scientific Committee on the Effects of Atomic Radiation. PMID- 17748754 TI - Formation of Elements in the Stars: To build all the elements requires that eight nuclear processes occur as the conditions become ripe. PMID- 17748756 TI - Erratum. AB - In the 1 August issue [Science 128, 24 (1958)] it was erroneously reported that Richmond K. Anderson of the Rockefeller Foundation and Harry C. Trimble of the Harvard Medical School had received honorary degrees from Harvard University. Anderson and Trimble received honorary doctor of science degrees from Cornell College. PMID- 17748757 TI - Accumulator Plants and Rock Weathering. PMID- 17748758 TI - Density Determinations Based on the Explorer and Vanguard Satellites. PMID- 17748759 TI - Density of the Upper Atmosphere. PMID- 17748760 TI - Publication versus Communication. PMID- 17748761 TI - Darwin and Pandora's Box. PMID- 17748763 TI - Equipment. PMID- 17748766 TI - THE USE OF POISONS AS FUNGICIDES AND INSECTICIDES. PMID- 17748764 TI - MOUNT ORIZABA OR CITLALTEPETL. PMID- 17748765 TI - THE VALUE OF A WATER ANALYSIS. PMID- 17748767 TI - STARFISHES OF THE INDIAN OCEAN. PMID- 17748768 TI - LIGHTHOUSE ILLUMINANTS. PMID- 17748769 TI - CURRENT NOTES ON ANTHROPOLOGY.--XXVII. PMID- 17748770 TI - THE COLLECTION OF FOSSIL MAMMALS IN THE AMERICAN MUSEUM OF NATURAL HISTORY, NEW YORK. PMID- 17748771 TI - Pivotal Sounds in Recollection. PMID- 17748772 TI - Tornadoes. PMID- 17748773 TI - Pre-Historic Remains in America. PMID- 17748774 TI - A Physiological Effect of Cave Visiting. PMID- 17748775 TI - Photographs of Botanists. PMID- 17748777 TI - The College Boards in Biology. PMID- 17748776 TI - singing of birds. PMID- 17748778 TI - Atoms for Peace. PMID- 17748779 TI - Simplicity and Clarity. PMID- 17748780 TI - The Primate Centers and Taxonomy. PMID- 17748781 TI - Tax Deductions. PMID- 17748782 TI - The Evolution of Science. PMID- 17748783 TI - The Care and Feeding of Intellectual Property: How much legal protection of "property rights" in ideas is desirable? AB - What can the researcher do to protect his ideas? Here the saying "It is a wise father that knows his own child" is applicable. Can a present-day researcher be sure that an idea is really his brain child? Let us assume, for the sake of argument, that this is possible; then his safest procedure is to keep that idea to himself until it can be submitted in a protectable package. Most universities and other non-profit research institutions lack patent policies sufficiently broad to be of much assistance to either the researcher or the institution. Possibly the first needed step in increasing the protection of research is a broadening of institutional patent policies to embrace property in ideas, even though ideas may not at present be patentable. Secondly, information regarding what institutions can do to assist in achieving protection of ideas should be disseminated as widely as possible. Thirdly, liaison should be established between the institution and Research Incorporated (32), or some similar nonprofit organization serving the educational community, in order that the developmental aspect of the idea may be guided at an early stage, so that when it is presented for commercial evaluation it will be in a protectable package and appropriately wrapped. PMID- 17748784 TI - Escape to the Endless Frontier: How can science be related to our political purposes and to our economic and constitutional system? PMID- 17748785 TI - Are We Really Telling the People about Science?: Science reporters are not doing well enough--scientists and science agencies often fail to help. PMID- 17748786 TI - The Method of Multiple Working Hypotheses: With this method the dangers of parental affection for a favorite theory can be circumvented. PMID- 17748787 TI - Education as a Way of Life: Traditional arrangements for education must be supplemented by a system designed for lifelong learning. PMID- 17748788 TI - Thoughts on Research. PMID- 17748789 TI - Security Practices: Nonmilitary Agencies Still Hold to Vestiges of Procedures Developed in 1950's. PMID- 17748790 TI - News in Brief: Hearings on NSF, Other Federal Programs, Announced; NAS to Study Accelerator Site. PMID- 17748791 TI - Summer: The "Climate" Is Changed for University Scientists and the Federal Government Did It. PMID- 17748792 TI - State Department: Rank, Authority of Science Office Is Emphasized. PMID- 17748793 TI - Origins of Central Andean Civilization: New Evidence. PMID- 17748794 TI - P. W. Bridgman and High-Pressure Physics. PMID- 17748795 TI - Biopsychology Comes of Age. PMID- 17748796 TI - Brain Research. PMID- 17748797 TI - Types of Articles for Science. PMID- 17748799 TI - News of Science. PMID- 17748798 TI - Recommendations for Development of Arid Lands. PMID- 17748800 TI - Acclimation of the Critical Thermal Maximum of the Reptile Urosaurus ornatus. PMID- 17748801 TI - Effect of N-m-Tolylphthalamic Acid on Tomato Flower Formation. PMID- 17748802 TI - Chalconatronite, a New Mineral from Egypt. PMID- 17748803 TI - Geologic Application of a Test for Citrate-Soluble Metals in Alluvium. PMID- 17748806 TI - Scientific Meetings. PMID- 17748804 TI - Miscellaneous Publications. PMID- 17748807 TI - Meetings & Conferences. AB - In the issue of 17 June, page 11A, the International Congress of Anthropological and Ethnological Sciences, 5th, was mistakenly announced for 2-9 Sept. This meeting will take place in 1956, not 1955. PMID- 17748808 TI - This week in science. PMID- 17748809 TI - Research and development in South Korea. PMID- 17748810 TI - Budget Crunch Stalls Super Collider: President Reagan's plan for building the world's largest particle accelerator is likely to remain stuck in the R&D phase in 1989 because of limited growth in funding for basic research. PMID- 17748812 TI - New Spy Satellites Urged for Verification: The Senate Intelligence Committee says the INF Treaty can be adequately verified but new systems are required to ensure compliance with a START treaty. PMID- 17748811 TI - Mars Mania and NASA. PMID- 17748813 TI - Hopes Recede for Early Ban on Chemical Arms: Although the United States and the Soviet Union have narrowed many of their differences, key issues remain unresolved and momentum has been lost. PMID- 17748814 TI - A French "joker in the pack". PMID- 17748816 TI - Troubled Times Ahead for Telescope-Makers: A proposed "new technology" telescope presents a classic choice between the old and new. PMID- 17748815 TI - Superconductors' Material Problems: The excitement over recent discoveries of new superconductors has tended to gloss over the serious material science problems that might hinder their practical application. PMID- 17748817 TI - Bigness: why and how. PMID- 17748818 TI - A European behemoth. PMID- 17748819 TI - 'Ain ghazal: a major neolithic settlement in central jordan. AB - 'Ain Ghazal, an archeological site located on the outskirts of Amman, Jordan, is one of the largest early villages known in the Near East. The site dates to the Neolithic period, during which mankind made one of its most significant advances, the adoption of domestic plants and animals as primary subsistence sources. Recent excavations at 'Ain Ghazal have augmented considerably current knowledge of several aspects of the Neolithic. Of particular interest has been the documentation of a continuous, or near continuous, occupation from early through late Neolithic components, and a concomitant dramatic economic shift. This shift was from a broad subsistence base relying on a variety of both wild and domestic plants and animals, to an economic strategy reflecting an apparent emphasis on pastoralism. PMID- 17748820 TI - Molecular/Organic ferromagnets. AB - Quantitative bulk ferromagnetic behavior has been established for the molecular/organic solid [Fe(III)(C(5)Me(5))(2)].(+)[TCNE].(-). Above 16 K the dominant magnetic interactions are along a 1-D chain and, near T(c), 3-D bulk effects as evidenced by the value of the critical exponents dominate the susceptibility. The extended McConnell model was developed and provides the synthetic chemist with guidance for making new molecular materials to study cooperative magnetic coupling in systems. Assuming the electron-transfer excitation arises from the POMO, ferromagnetic coupling by the McConnell mechanism requires stable radicals (neutral, cations/anions, or ions with small diamagnetic counterions) with a non-half-filled POMO. The lowest excited state formed via virtual charge transfer (retro or forward) must also have the same spin multiplicity and mix with the ground state. These requirements limit the structure of a radical to D(2d) or C>/=(3) symmetry where symmetry breaking distortions do not occur. Intrinsic doubly and triply degenerate orbitals are not necessary and accidental degeneracies suffice. To achieve bulk ferromagnetism, ferromagnetic coupling must be established throughout the solid and a microscopic model has been discussed. These requirements are met by [Fe(III)(C(5)Me(5))(2)].(+)[TCNE].(-). Additionally this model suggests that the Ni(III) and Cr(III) analogs should be antiferromagnetic and ferrimagnetic, respectively, as preliminary data suggest. Additional studies are necessary to test and further develop the consequences of these concepts. Some molecular/organic solids comprised of linear chains of alternating metallocenium donors (D) and cyanocarbon acceptors (A) with spin state S = 1/2 (...D.(+)A.( )D.(+)A.(-)...) exhibit cooperative magnetic phenomena, that is, ferro-, antiferro-, ferri-, and metamagnetism. For [Fe(III)(C(5)Me(5))(2)].(+)[TCNE](-). (Me = methyl; TCNE = tetracyanoethylene), bulk ferromagnetic behavior is observed below the Curie temperature of 4.8 K. A model of configuration mixing of the lowest charge-transfer excited state with the ground state was developed to understand the magnetic coupling as a function of electron configuration and direction of charge transfer. This model predicts that ferromagnetic coupling requires stable radicals with a non-half-filled degenerate valence orbital and a charge-transfer excited state with the same spin multiplicity that mixes with the ground state. Ferromagnetic coupling must dominate in all directions to achieve a bulk ferromagnet. Thus, the primary, secondary, and tertiary structures are crucial considerations for the design of molecular/organic ferromagnets. PMID- 17748821 TI - Short-Lived s-Process Gamma-Ray Lines in Type II Supernovae. AB - The nuclear abundances in the helium-burning shells of presupernova stellar models are calculated. For stars of over 20 solar masses the (22)Ne(alpha,n)(23) Mg reaction produces enough neutrons on a sufficiently short time scale for the s process to produce (59)Fe (half-life = 45 days) and (60)Co (half-life = 5.3 years). These isotopes are expected to survive the passage of the shock, and gamma rays from their decays should be detectable from most galactic type II supernovae with the NASA Gamma Ray Observatory. Because of its great distance and low metallicity, these lines are not expected to be observable from supernova 1987A. PMID- 17748822 TI - Molecular-Level Control over Surface Order in Self-Assembled Monolayer Films of Thiols on Gold. AB - Long-chain omegahydroxyalkanethiols [HS(CH(2))nOH] coordinate to gold surfaces through the sulfur atom and produce ordered, hydrophilic monolayers in which the hydroxyl groups are exposed at the outer surface. Coadsorption of two omega hydroxyalkanethiols of different chain lengths n resulted in the formation of a monolayer having a disordered surface region that was markedly less hydrophilic than the homogeneous, hydroxylic surface formed from either pure compound. By controlling the composition of the monolayer, it was also possible to control simultaneously the degree of order in the surface and its hydrophilicity. In the monolayers containing a mixture of alkanethiol components, these components apparently did not phase-segregate into macroscopic islands, but were dispersed on a molecular scale. assistance and many useful discussions. PMID- 17748823 TI - Mussel growth supported by methane as sole carbon and energy source. AB - Symbioses between chemoautotrophic bacteria and several specialized marine invertebrates are well documented. However, none of these symbioses have been demonstrated to provide sufficient energy and carbon to the host to enable it to grow. Growth rates of seep mussels collected from hydrocarbon seeps off the coast of Louisiana were measured in a controlled environment where methane was the sole carbon and energy source. The growth rates increased to a maximum of 17.2 micrometers per day in response to methane and approached zero in the absence of methane. These mussels contain methanotrophic symbiotic bacteria in their gills, which suggests that these bacteria provide their hosts with a net carbon flux originating from methane. PMID- 17748824 TI - Listing of women in science groups gets update. PMID- 17748825 TI - Members help museums fulfill mission. PMID- 17748826 TI - Ethics in graduate education studied. PMID- 17748827 TI - New art show opens. PMID- 17748828 TI - Role models sought. PMID- 17748829 TI - 1988 science education directory available. PMID- 17748830 TI - Obituaries. PMID- 17748831 TI - Ethics report begins publication. PMID- 17748832 TI - AAAS, Harvard Hold Science Policy Workshop. PMID- 17748833 TI - Coming Soon--AAAS Member Survey. PMID- 17748834 TI - Insured members enjoy cost savings. PMID- 17748835 TI - Cultural behaviors and their sites: method and theory for activity area research. PMID- 17748836 TI - Near eastern settlement: the archaeology of Western iran. PMID- 17748837 TI - Social formations in Africa: the african frontier. PMID- 17748838 TI - Products & materials. PMID- 17748839 TI - Meetings & Conferences. PMID- 17748840 TI - Increased Translocation of Plant-Growth-Modifying Substances Due to Application of Boron. PMID- 17748841 TI - The Odors of Optical Isomers. PMID- 17748842 TI - The Research Committee in the Organization of the International Biological and Medical Associations and their Congresses. PMID- 17748843 TI - "Data". PMID- 17748844 TI - Food Prices in Palo Alto. PMID- 17748845 TI - Lepidurus kirkii. PMID- 17748847 TI - A Century of Geography. PMID- 17748846 TI - Description of a New Technique for Rearing Polychaetous Annelids to Sexual Maturity. PMID- 17748848 TI - Publications Received. PMID- 17748849 TI - The Support of Research in Medical and Allied Fields for the Period 1946 through 1951. PMID- 17748850 TI - Some Applications of the Rapid Uptake of Vitamin B12 by Resting Lactobacillus leichmannii Organisms. PMID- 17748851 TI - On the Interaction of Mesons and Plural vs. Multiple Meson Production. PMID- 17748852 TI - A Rapid Titrimetric Method for Determining the Water Content of Animal Tissues. PMID- 17748853 TI - Bone Implantation as a Means of Studying Vitamin D Action. PMID- 17748854 TI - The Critical Frequency of Taste. PMID- 17748855 TI - Skeletal Units in Protein Crystals. PMID- 17748856 TI - An Inhibitor of Desoxyribonuclease in Human White Blood Cells and Bone Marrow Cells and its Relationship to Cellular Maturity. PMID- 17748857 TI - Action of Chymotrypsin agr and Chymotrypsin B upon Several Protein Substrates. PMID- 17748859 TI - Religion and Higher Education. PMID- 17748858 TI - Rejuvenation Re-evaluated. PMID- 17748860 TI - Potentiometric Measurements in Colloidal Systems. PMID- 17748861 TI - A Practical Laboratory Method for Mass Culturing Bacteria. PMID- 17748863 TI - William Herbert Hobbs: 1864-1953. PMID- 17748862 TI - CIBA Tissue Transplantation Symposium. PMID- 17748864 TI - Observations on a Class of Free Radicals Derived from Aromatic Compounds. PMID- 17748865 TI - The Scientist and the Library Cataloger. PMID- 17748866 TI - This week in science. PMID- 17748867 TI - Science in Japan. PMID- 17748868 TI - Sciencescope. PMID- 17748869 TI - You Can't Tell the Players Without.. PMID- 17748870 TI - How should ;therapeutic vaccines' be tested? PMID- 17748872 TI - Outcry shoots down funding reform. PMID- 17748871 TI - Study flunks science and math tests. PMID- 17748873 TI - U.s. Epidemics: the price neglect? PMID- 17748874 TI - Theoreticians are putting a new spin on the planets. PMID- 17748875 TI - Found: messengers from the interstellar medium. PMID- 17748877 TI - Combining economics with biodiversity. PMID- 17748876 TI - Doctors take on the environment. PMID- 17748878 TI - Hard-won victory over wheat blight. PMID- 17748879 TI - German gene regs hit snag. PMID- 17748880 TI - Science in Japan. PMID- 17748881 TI - Big spender, but little basic clout. PMID- 17748882 TI - Japanese academics bemoan the cost of years of neglect. PMID- 17748883 TI - Women Scientists: It's Lonely at the Top. PMID- 17748884 TI - Breaking barriers and expanding frontiers. PMID- 17748885 TI - Industry steps in to fill the gap in basic research. PMID- 17748886 TI - If at first you don't succeed.. PMID- 17748887 TI - Has tsukuba put its worst days behind it? PMID- 17748888 TI - Bright dreams despite a legacy of hits and misses. PMID- 17748889 TI - The Real World Computing Program: MITI's Next Computer Research Initiative. PMID- 17748890 TI - Public and private support of basic research in Japan. PMID- 17748891 TI - Organic synthesis: current status in Japan. PMID- 17748892 TI - Has Japan begun to move toward atomic level material processing? PMID- 17748893 TI - Astronomy in Japan. PMID- 17748894 TI - The challenge of joint research in Japan. PMID- 17748895 TI - Underfunding of basic science in Japan. PMID- 17748896 TI - The yohkoh mission for high-energy solar physics. AB - The Japanese Yohkoh satellite is now in orbit observing the sun with a set of x ray imagers and x-ray and gamma-ray spectrometers. The data from this successful mission provide new information on solar flares and the sun's corona. This paper discusses the Yohkoh observations and presents a sample of the first scientific results from the mission. PMID- 17748897 TI - Seismic Tomogram of the Earth's Mantle: Geodynamic Implications. AB - Recent seismic tomography of the Earth's mantle has revealed a large-scale pattern of mantle convection comprising upwelling columnar plumes in the Pacific and Africa and downwelling planar sheets along the Circum Pacific. Upwelling and downwelling occur most extensively under the south Pacific and west Pacific, respectively. High-resolution image of plate subduction has been obtained from the dense seismic networks around Japan. Japanese seismologists are in the best position to resolve the internal structure of downwelling current as an integral part of the whole convection system. PMID- 17748898 TI - Mercury radar imaging: evidence for polar ice. AB - The first unambiguous full-disk radar mapping of Mercury at 3.5-centimeter wavelength, with the Goldstone 70-meter antenna transmitting and 26 antennas of the Very Large Array receiving, has provided evidence for the presence of polar ice. The radar experiments, conducted on 8 and 23 August 1991, were designed to image the half of Mercury not photographed by Mariner 10. The orbital geometry allowed viewing beyond the north pole of Mercury; a highly reflective region was clearly visible on the north pole during both experiments. This polar region has areas in which the circular polarization ratio (pt) was 1.0 to 1.4; values < approximately 0.1 are typical for terrestrial planets. Such high values of have hitherto been observed in radar observations only from icy regions of Mars and icy outer planet satellites. PMID- 17748899 TI - Radar mapping of mercury: full-disk images and polar anomalies. AB - A random-code technique has been used at Arecibo to obtain delay-Doppler radar images of the full disk of Mercury. Anomalously bright features were found at the north and south poles. The north polar feature is oblong (4 degrees by 8 degrees ) and offset from the pole. The smaller south polar feature is mostly confined to the floor of the crater Chao Meng-Fu. The polar locations and radar properties of these features indicate that they may be produced by volume scattering in ice. The images also reveal a variety of more subdued reflectivity features ranging in size from hundreds to thousands of kilometers; some of these appear to have an impact origin. PMID- 17748900 TI - The thermal stability of water ice at the poles of mercury. AB - Recent radar observations of Mercury have revealed the presence of anomalous radar reflectivity and polarization features near its north and south poles. Thermal model calculations show that, despite Mercury's proximity to the sun, the temperatures of flat, low-reflectivity surfaces at Mercury's poles are not expected to exceed 167 kelvin. The locations of the anomalous polar radar features appear to be correlated with the locations of large, high-latitude impact craters. Maximum surface temperatures in the permanently shadowed regions of these craters are expected to be significantly colder, as low as 60 kelvin in the largest craters. These results are consistent with the presence of water ice, because at temperatures lower than 112 kelvin, water ice should be stable to evaporation over time scales of billions of years. PMID- 17748901 TI - Biological weighting function for the inhibition of phytoplankton photosynthesis by ultraviolet radiation. AB - Severe reduction of stratospheric ozone over Antarctica has focused increasing concern on the biological effects of ultraviolet-B (UVB) radiation (280 to 320 nanometers). Measurements of photosynthesis from an experimental system, in which phytoplankton are exposed to a broad range of irradiance treatments, are fit to an analytical model to provide the spectral biological weighting function that can be used to predict the short-term effects of ozone depletion on aquatic photosynthesis. Results show that UVA (320 to 400 nanometers) significantly inhibits the photosynthesis of a marine diatom and a dinoflagellate, and that the effects of UVB are even more severe. Application of the model suggests that the Antarctic ozone hole might reduce near-surface photosynthesis by 12 to 15 percent, but less so at depth. The experimental system makes possible routine estimation of spectral weightings for natural phytoplankton. PMID- 17748902 TI - Response. PMID- 17748903 TI - Theory and experiment in high-temperature superconductivity. PMID- 17748905 TI - Science in Japan: some books. PMID- 17748904 TI - Technomiracles revisited. PMID- 17748907 TI - An era of electro-optics. PMID- 17748908 TI - PRODUCTS & MATERIALS. PMID- 17748906 TI - After the wall. PMID- 17748909 TI - RESEARCH IN THE MEDICAL SCIENCES. PMID- 17748910 TI - "THE FRIENDLY ARCTIC". PMID- 17748911 TI - NATIONAL RESEARCH FELLOWSHIPS IN THE BIOLOGICAL SCIENCES. PMID- 17748913 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17748912 TI - AN UNUSUAL OCCURRENCE OF ROCK BORING MOLLUSKS IN CONCRETE ON THE PACIFIC COAST. PMID- 17748914 TI - AN INTERESTING LIVERWORT. PMID- 17748916 TI - COAL BALLS. PMID- 17748915 TI - A FUND FOR GERMAN AND AUSTRIAN LABORATORIES RAISED BY THOSE WHO HAVE WORKED IN THEM. PMID- 17748917 TI - THE INITIAL ENERGY OF THERMIONIC ELECTRONS. PMID- 17748918 TI - THE AMERICAN PHYSIOLOGICAL SOCIETY. PMID- 17748919 TI - MYTHOLOGY AND AMERICAN MYTHS. PMID- 17748921 TI - SCIENTIFIC NEWS IN WASHINGTON. PMID- 17748920 TI - Shad-Hatching. PMID- 17748922 TI - United States Fish Commission Work on the Pacific Coast. PMID- 17748923 TI - The Water-Spouts of April. PMID- 17748924 TI - ELECTRICAL SCIENCE. PMID- 17748926 TI - MENTAL SCIENCE. PMID- 17748925 TI - HEALTH MATTERS. PMID- 17748927 TI - Composite Portraiture of the Insane. PMID- 17748928 TI - Experiments in Vision again. PMID- 17748929 TI - The Significance of 'Variety' and 'Species.'. PMID- 17748930 TI - The Ohio Mounds. PMID- 17748931 TI - Is There Underinvestment in Education? PMID- 17748932 TI - Biophysics of Bird Flight. PMID- 17748934 TI - The Democratic Convention: Kennedy's Brain Trust and His Plans for a " New" New Deal. PMID- 17748933 TI - How Did Life Begin? PMID- 17748935 TI - Medicinal Chemistry Study Group. PMID- 17748936 TI - Translation Program. PMID- 17748938 TI - Sound Production by the Satinfin Shiner, Notropis analostanus, and Related Fishes. AB - Several sounds are produced by minnows. Only one is not of purely mechanical origin, and it is classed as a "biological" sound. This sound is variously produced by males when fighting and chasing as well as during courtship. Females emit a similar sound. Testosterone injections and elevated temperatures result in an increased rate of biological sound emission. PMID- 17748937 TI - First Natural Occurrence of Coesite. AB - Coesite, the high-pressure polymorph of SiO(2), hitherto known only as a synthetic compound, is identified as an abundant mineral in sheared Coconino sandstone at Meteor Crater, Arizona. This natural occurrence has important bearing on the recognition of meteorite impact craters in quartz-bearing geologic formations. PMID- 17748939 TI - Avoidance Conditioning and Alcohol Consumption in Rhesus Monkeys. AB - Measures of intake of water and of a solution of 20-percent alcohol in water were determined in rhesus monkeys before, during, and after avoidance training. Alcohol consumption increased during, and decreased after, avoidance sessions. Water intake remained the same or decreased during avoidance sessions and stayed at this level after the sessions. PMID- 17748940 TI - An All-round Soil Percolator. AB - A description is given of a soil percolator which has been used both for instructional purposes and for microbiological research and has been found accurate and easy to operate. It could be used for aerobic and anaerobic experiments with a soil under water-saturated conditions. PMID- 17748941 TI - Lethal Effect of Visible Light on Cavernicolous Ostracods. AB - Light intensities of the order of 1/20th that of normal sunlight are sufficient to kill ostracods from two different caves. Loss of physiological protection against light has probably occurred through the same mechanism which has resulted in the much better known loss of morphological characters in cave animals. PMID- 17748942 TI - Forthcoming Events. PMID- 17748943 TI - Artificial Biosphere. PMID- 17748944 TI - Letters to the Editor. PMID- 17748945 TI - Letters to the Editor. PMID- 17748946 TI - Letters to the Editor. PMID- 17748947 TI - Hazards and Insecticides. PMID- 17748949 TI - Conversions. PMID- 17748948 TI - Electronic Brains? PMID- 17748950 TI - COMMENT AND CRITICISM. PMID- 17748952 TI - Anthropos and anthropopithecus. PMID- 17748951 TI - LETTERS TO THE EDITOR. PMID- 17748954 TI - The Yellowstone Park as a bison preserve. PMID- 17748953 TI - The muskrat carnivorous. PMID- 17748955 TI - THE GEORGIA WONDER-GIRL AND HER LESSONS. PMID- 17748957 TI - THE 'COMMA BACILLUS' OF KOCH. PMID- 17748956 TI - THE NANTUCKET MUSEUM. PMID- 17748958 TI - LIGHTHOUSE ILLUMINANTS. PMID- 17748959 TI - THE ESSEX DENEHOLES. PMID- 17748960 TI - RECENT AFRICAN EXPLORATION. PMID- 17748961 TI - INGERSOLL'S COUNTRY COUSINS. PMID- 17748962 TI - THE FORESTS OF THE UNITED STATES. PMID- 17748963 TI - SCHELLEN'S DYNAMO-ELECTRIC MACHINES. PMID- 17748964 TI - BARNARD'S PYRAMID OF GIZEH. PMID- 17748965 TI - Letter to the editor. PMID- 17748967 TI - Adequate protection. PMID- 17748966 TI - Modern taxonomy. PMID- 17748968 TI - Letter to the editor. PMID- 17748969 TI - Letter to the editor. PMID- 17748970 TI - Come, now, and let us reason together. PMID- 17748971 TI - Gravitation Theory: Empirical Status from Solar System Experiments: All observations to date are consistent with Einstein's general relativity theory of gravity. AB - I have reviewed the historical and contemporary experiments that guide us in choosing a post-Newtonian, relativistic gravitational theory. The foundation experiments essentially constrain gravitation theory to be a metric theory in which matter couples solely to one gravitational field, the metric field, although other cosmological gravitational fields may exist. The metric field for any metric theory can be specified (for the solar system, for our present purposes) by a series of potential terms with several parameters. A variety of experiments specify (or put limits on) the numerical values of the seven parameters in the post-Newtonian metric field, and other such experiments have been planned. The empirical results, to date, yield values of the parameters that are consistent with the predictions of Einstein's general relativity. PMID- 17748972 TI - Evaluation of Infant Intelligence: Infant intelligence scores--true or false? PMID- 17748974 TI - H. Allen Smith Jet Propulsion Lab--or What's in a Name? PMID- 17748973 TI - Grant termination: scientist wins $16 million for loss of support. PMID- 17748975 TI - Los alamos scientific laboratory: weapons are still the focus. PMID- 17748977 TI - U.N. Environmental program: despite hitch, coming on strong. PMID- 17748976 TI - LASL Directors, Past and Present. PMID- 17748978 TI - Crusades on cancer: a doubting view. PMID- 17748980 TI - Cyclic AMP in Brain: Role in Synaptic Transmission. PMID- 17748979 TI - Energy needs: projected demands and how to reduce them. PMID- 17748982 TI - Gravitational effects on concentrations and partial pressures in solutions: a thermodynamic analysis. AB - Thermodynamic analysis establishes the equilibrium relationships between the concentrations and partial pressures of the components of liquid and gaseous solutions in the presence of a gravitational field. The conditions of equilibrium between a column of gas and gas-saturated water and the conditions of equilibrium governing a model of the distribution of radioactive heat sources in surface rocks are deduced from the theory. PMID- 17748981 TI - Temperature regulation by the inflorescence of philodendron. AB - The inflorescence of Philodendron selloum temporarily maintains a core temperature of 38 degrees to 46 degrees C, despite air temperatures ranging from 4 degrees to 39 degrees C, by means of a variable metabolic rate. The heat is produced primarily by small, sterile male flowers that are capable of consuming oxygen at rates approaching those of flying hummingbirds and sphinx moths. PMID- 17748983 TI - Nitrogen fixation by a blue-green epiphyte on pelagic sargassum. AB - Nitrogen fixation by Dichothrix fucicola, an epiphyte on pelagic Sargassum, was measured in May and June 1972 in the western Sargasso Sea and the Gulf Stream. This is the first report of nitrogen fixation by a heterocyst-bearing blue-green alga in the open ocean, and also the first observation of nitrogen fixation in the genus Dichothrix. Cellular carbon/nitrogen ratios suggested that the Dichothrix was nitrogen-starved. In dense aggregations of Sargassum, such as rafts or windrows, the enrichment of surface seawater with combined nitrogen from nitrogen fixation may be pronounced. PMID- 17748984 TI - Ultraviolet reflection of a male butterfly: interference color caused by thin layer elaboration of wing scales. AB - Males of the butterfly Eurema lisa, like many other members of the family Pieridae, reflect ultraviolet light. The color is structural rather than pigmentary, and originates from optical interference in a microscopic lamellar system associated with ridges on the outer scales of the wing. The dimensions and angular orientation of the lamellar system conform to predictions based on physical measurement of the spectral characteristics, including "color shifts" with varying angles of incidence, of the reflected ultraviolet light. The female lacks such scales and is consequently nonreflectant. The ultraviolet dimorphism supposedly serves as the basis for sexual recognition in courtship. PMID- 17748986 TI - SCIENCE NEWS. PMID- 17748985 TI - Observational learning and social facilitation in the rat. AB - Learning by rats was facilitated when response-relevant cues were provided by other rats; learning increased as a function of number of cues provided. These results suggest that rats can learn by imitation. Learning by rats that observed conspecifics not emitting response-relevant cues was retarded compared to learning by rats that did not observe conspecifics. This indicates that a conspecific's presence can also inhibit learning, a result consistent with social facilitation theory. PMID- 17748987 TI - THE ST. LOUIS MEETING OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE AND ASSOCIATED SOCIETIES. PMID- 17748988 TI - REPORT OF THE COMMITTEE ON GRANTS. PMID- 17748989 TI - COMMENT AND CRITICISM. PMID- 17748990 TI - Nutritive value of cellulose. PMID- 17748991 TI - Mental capacity of an infant. PMID- 17748992 TI - Sir William Thomson's Molecular dynamics. PMID- 17748994 TI - An attempt to photograph the corona. PMID- 17748993 TI - LETTERS TO THE EDITOR. PMID- 17748995 TI - The naval observatory publications. PMID- 17748997 TI - The cold weather of February and March. PMID- 17748996 TI - CIVIL AND ASTRONOMICAL TIME. PMID- 17748998 TI - THE SCIENTIFIC RESULTS OF THE LADY FRANKLIN BAY EXPEDITION. PMID- 17748999 TI - FOOTPRINTS IN THE ROCKS OF COLORADO. PMID- 17749000 TI - SUCCESSFUL EXTRACTION OF A BULLET FROM THE BRAIN. PMID- 17749001 TI - THE DEBATE ON VIVISECTION AT OXFORD. PMID- 17749002 TI - JAMES CLERK MAXWELL. PMID- 17749003 TI - THE ROYAL ASTRONOMICAL SOCIETY OF LONDON. PMID- 17749004 TI - THE PART PLAYED BY THE CELL IN LIVING ORGANISMS. PMID- 17749005 TI - LANGLEY'S WORK ON MOUNT WHITNEY. PMID- 17749006 TI - This week in science. PMID- 17749007 TI - Space science crunch. PMID- 17749008 TI - Space science crunch. PMID- 17749009 TI - Sciencescope. PMID- 17749010 TI - Livermore lab chief nuckolls resigns under pressure. PMID- 17749012 TI - Deep-trench research waits on balky Japanese submersible. PMID- 17749011 TI - Livermore physicists ask for the sun. PMID- 17749013 TI - In pittsburgh, physicists get down to the nitty-gritty. AB - While some physicists ponder the grand design of the universe, others delve to the atomic scale. That microrealm was the focus of most of the 5300 researchers specializing in biological and condensed-matter physics and in materials science who gathered in Pittsburgh two weeks ago for the annual March meeting of the American Physical Society (APS). Among the more than 5000 papers presented at the meeting were descriptions of building and measuring micromagnets, making atomic movies, and studying sand grains for clues to why some dunes roar. PMID- 17749014 TI - Ecologists dare to ask: how much does diversity matter? PMID- 17749015 TI - Senate rejects overhead cost freeze. PMID- 17749016 TI - Peddling for underwater glory. PMID- 17749017 TI - Canada-France EMF Study Inconclusive. PMID- 17749018 TI - NSF Wants an Education Think Tank. PMID- 17749019 TI - Modulated magnetic phases in rare Earth metallic systems. AB - Neutron scattering has played a key role in the microscopic understanding of the static and dynamic properties of magnetic materials. Modulated magnetic structures first discovered in the late fifties can no longer be referred to as exotic; more than a hundred such phases have already been found in a variety of magnetic systems. Neutron and x-ray magnetic scattering have played a complementary role in the recent discovery and understanding of the modulated magnetic phases in rare earth metallic systems. PMID- 17749020 TI - Stellar luminosity variations and global warming. AB - Recent studies indicate that variation in the sun's luminosity is less than that observed in many other stars of similar magnetic activity. Current findings also indicate that in more active stars, the attenuation by faculae of sunspot luminosity modulation is less effective than in the sun at present. The sun could thus become photometrically more variable (and dimmer) if its magnetic activity exceeded present levels. But the levels of solar activity required for this to occur are not observed in carbon-14 and beryllium-10 records over the past several millennia, which indicates that such an increase in amplitude of surface magnetism-driven variations in solar luminosity is unlikely in the present epoch. PMID- 17749021 TI - Trends in Stomatal Density and 13C/12C Ratios of Pinus flexilis Needles During Last Glacial-Interglacial Cycle. AB - Measurements of stomatal density and delta(13)C of limber pine (Pinus flexilis) needles (leaves) preserved in pack rat middens from the Great Basin reveal shifts in plant physiology and leaf morphology during the last 30,000 years. Sites were selected so as to offset glacial to Holocene climatic differences and thus to isolate the effects of changing atmospheric CO(2) levels. Stomatal density decreased approximately 17 percent and delta(13)C decreased approximately 1.5 per mil during deglaciation from 15,000 to 12,000 years ago, concomitant with a 30 percent increase in atmospheric CO(2). Water-use efficiency increased approximately 15 percent during deglaciation, if temperature and humidity were held constant and the proxy values for CO(2) and delta(13)C of past atmospheres are accurate. The delta(13)C variations may help constrain hypotheses about the redistribution of carbon between the atmosphere and biosphere during the last glacial-interglacial cycle. PMID- 17749022 TI - Quantifying global warming from the retreat of glaciers. AB - Records of glacier fluctuations compiled by the World Glacier Monitoring Service can be used to derive an independent estimate of global warming during the last 100 years. Records of different glaciers are made comparable by a two-step scaling procedure: one allowing for differences in glacier geometry, the other for differences in climate sensitivity. The retreat of glaciers during the last 100 years appears to be coherent over the globe. On the basis of modeling of the climate sensitivity of glaciers, the observed glacier retreat can be explained by a linear warming trend of 0.66 kelvin per century. PMID- 17749023 TI - Molecular Nanotube Aggregates of beta- and ggr-Cyclodextrins Linked by Diphenylhexatrienes. AB - Linked by strings of diphenylhexatriene (DPH) molecules, beta- and gamma cyclodextrins (CDs) can form nanotube aggregates that contain as many as approximately 20 betaCDs (20 nanometers long) or approximately 20 to 35 gammaCDs (20 to 35 nanometers long). Nanotube formation was indicated in solution, by fluorescence anisotropy and light scattering results, and on graphite surfaces, by scanning tunneling microscopy. Tubes were not observed for the smaller alphaCDs. Molecular modeling shows that CD cavity size and the rodlike DPH structure are key factors in nanotube formation. Spectra generated by proton nuclear magnetic resonance indicate the inclusion of DPH in the interior of the CDs and formation of nanotubes in betaCDs and gammaCDs only. The photophysical properties of DPH are affected by its arrangement into a one-dimensional array within the CD nanotube, possibly because of exciton formation. PMID- 17749024 TI - High-Pressure Melting of (Mg,Fe)SiO3-Perovskite. PMID- 17749025 TI - Response. PMID- 17749026 TI - Statistical analyses of soil quality. PMID- 17749027 TI - Response. PMID- 17749028 TI - Big systems. PMID- 17749029 TI - Vignettes: foundations of economics. PMID- 17749030 TI - Thoughtplay. PMID- 17749031 TI - Molluscan dwellings. PMID- 17749033 TI - Products & materials. PMID- 17749032 TI - Probing biological surfaces. PMID- 17749034 TI - THE MODERN SYSTEMATIST. PMID- 17749035 TI - PATENT REFORM PROSPECTS. PMID- 17749036 TI - THE PITTSBURGH MEETING OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17749037 TI - THE BEARING OF THE FACTS REVEALED BY ANTARCTIC RESEARCH UPON THE PROBLEMS OF THE ICE AGE. PMID- 17749039 TI - CONCERNING THE INFLUENCE OF THE AGE OF AN ORGANISM IN MAINTAINING ITS ACID-BASE EQUILIBRIUM. PMID- 17749040 TI - BOSTON MEETING OF THE AMERICAN CHEMICAL SOCIETY. V. PMID- 17749038 TI - EFFICIENT LABORATORY LIGHTING. PMID- 17749042 TI - Lake Agassiz and the Mankato-Valders Problem. PMID- 17749041 TI - The Long Pull. PMID- 17749043 TI - Ward Vinton Evans, Physical Chemist. PMID- 17749045 TI - Meetings and Societies. PMID- 17749044 TI - News of Science. PMID- 17749046 TI - EQUIPMENT NEWS. PMID- 17749047 TI - Auroral Research. PMID- 17749048 TI - Body Composition: Studies in the Human Being by the Dilution Principle. PMID- 17749049 TI - Observations on the Supposed Intracellular Symbiotic Microorganisms of Aphids. PMID- 17749050 TI - Determination of Specific Activities of Cl4-Labeled Organic Compounds with a Water-Soluble Liquid Scintillator. PMID- 17749051 TI - Survival and Growth of Human Tissues Transplanted to Hamster Cheek Pouch. PMID- 17749052 TI - Sedimentation and Flexibility of Sodium Thymonucleate Molecule. PMID- 17749053 TI - Variation in Coloring Rates of Tobacco. PMID- 17749054 TI - Fasciae Dorsi Variants. PMID- 17749055 TI - A Simple Method for Staining Trypanosomes and Plasmodia of Malaria in Tissue Sections. PMID- 17749056 TI - The Irradiation-Induced Autoxidation of Linoleic Acid. PMID- 17749057 TI - Biological or Psychological Warfare? PMID- 17749058 TI - International Code of Zoological Nomenclature: Proposed Amplification, Clarifications, and Extensions to be Considered by the International Congress of Zoology, Copenhagen 1953. PMID- 17749059 TI - Letter to the editor. PMID- 17749060 TI - Letter to the editor. PMID- 17749062 TI - Student unrest. PMID- 17749061 TI - Letter to the editor. PMID- 17749063 TI - Farming Systems and Political Growth in Ancient Oaxaca: Physiographic features and water-control techniques contributed to the rise of Zapotec Indian civilization. AB - The Valley of Oaxaca's large flat floor, high water table, low erosion rate, and frost-free floodplain give it a higher agricultural potential than that of most surrounding areas. The development of the pot-irrigation system early in the Formative period gave it a head start over other valleys, where the low water table did not permit such farming; Oaxaca maintained its advantage by assimilating canal irrigation, barbecho, infield-outfield systems, flood-water farming, and hillside terracing as these methods arose. With the expansion of population in the high-water-table zone of the high alluvium, competition for highly productive land and manipulation of surpluses may have led to initial disparities in wealth and status; competition probably increased when canal irrigation systems were added during the Middle Formative, improving some localities to the point where one residental group owned land more valuable than that of its neighbors. PMID- 17749065 TI - Haldan keffer hartline. AB - By the methods of comparative physiology, or of experimental biology, by the choice of a suitable organ, tissue or process, in some animal far removed in evolution, we may often throw light upon some function or process in the higher animals, or in man. PMID- 17749064 TI - Ragnar granit. AB - If it shall be demanded, then, when a man begins to have any ideas? I think the true answer is, when he first has any sensation. For since there appear not to be any ideas in the mind before the senses have conveyed any in, I conceive that ideas in the understanding are coeval with sensation. . . . PMID- 17749067 TI - Federal economizing: house votes to take it out of R & d. PMID- 17749068 TI - Academic freedom: judges support student rights. PMID- 17749069 TI - Mendelevium: divalency and other chemical properties. AB - Mendelevium (element 101) is the first actinide element found to give a divalent ion stable in solution. Reduction from the 3+ oxidation state was accomplished with Zn dust, Zn-Hg amalgam, Cr(2+), Eu(2+), and V(2+); additionally, measurements of the equilibrium with V(2+) provided an estimate of +0.2 volt for the couple, Md(2+) = Md(3+) + e(-). The chemical behavior of Md(3+) is similar to that of the other trivalent actinides and lanthanides. Oxidation from the trivalent to higher valence states with sodium bismuthate was not detected. PMID- 17749070 TI - Wax microchannels in the epidermis of white clover. AB - The application of conventional electron microscopy to the study of plant leaves and fruit readily displays the surface wax deposits, but not the wax pathways from the underlying cells. A modified freeze-etch technique shows both at the same time and indicates that wax is transported from the epidermal cells to the leaf surface in microchannels. PMID- 17749071 TI - Genetic Homologies and Drift within Population of DNA Molecules. PMID- 17749072 TI - Proton-Proton Elastic Scattering and Structure within the Proton. PMID- 17749074 TI - Mutational evidence for controlled genic activity as a mechanism of differentiation. PMID- 17749073 TI - Further studies on memory formation in the goldfish. PMID- 17749075 TI - Recent developments in thermoelectricity. PMID- 17749076 TI - Selective Autolysis of Nuclei as a Source of DNA Precursors for Other Nuclei within the Same Cell. PMID- 17749077 TI - Implications of curvilinearity in the relationship of efficiency of performance to strength of motivation for studies of individual differences in achievement related motives. PMID- 17749078 TI - Diagnosis of normokalemic primary aldosteronism, a new form of curable hypertension. PMID- 17749079 TI - Occurrence of similar sets of transport agencies for amino acids in various cells. PMID- 17749080 TI - Possible triradiate background of some echinoderms and its bearing on phylogeny. PMID- 17749081 TI - Complementary functioning of two components required for the reduction of n2 from four nitrogen-fixing bacteria. PMID- 17749083 TI - Pathophysiological consequences of increased gastric mucosal permeability to Acid. PMID- 17749082 TI - Regulatory variants in eucaryotes. PMID- 17749084 TI - Infection experiments with a fungus (coelomomyces) which kills malarial mosquitoes. PMID- 17749086 TI - Influenza virus envelope protein: biological activity as a function of reassociation. PMID- 17749085 TI - An evaluation of the role of carnitine in regulating Fatty Acid oxidation and gluconeogenesis. PMID- 17749087 TI - First-stage electrical effects in vision. PMID- 17749088 TI - How ciliary Basal bodies develop. PMID- 17749089 TI - Neutron activation studies of the source of prehistoric hopewellian obsidian implements from the middle west. PMID- 17749090 TI - Molecular basis of carcinogenesis by human adenoviruses. PMID- 17749091 TI - Organization of DNA in chromosomes of eucaryotes. PMID- 17749092 TI - Estrogen-binding substances of target tissues. PMID- 17749093 TI - Pyridine nucleotide in mung bean mitochondria. PMID- 17749094 TI - Hormones in reproduction and teratology in Guinea pigs. PMID- 17749095 TI - Excretion of ketosteroids and proneness to breast cancer. PMID- 17749096 TI - Hydrogen bonding of C - h * * * o = C in proteins. PMID- 17749097 TI - Genetically controlled diploidy in a higher fungus. PMID- 17749098 TI - Cinephotomicrography of starch contents of tomato tissue culture cells in microculture. PMID- 17749099 TI - A cosmic ray program for the study of strong interaction physics in the range of 100 to 1000 gev. PMID- 17749100 TI - Neural coordination in a simple ganglion. PMID- 17749101 TI - Chemical ecology: fungus-growing ants. PMID- 17749102 TI - Antigenic behavior of cytochrome C. PMID- 17749103 TI - A temperature-sensitive mutant affecting phage DNA synthesis and lysogenization. PMID- 17749104 TI - Tubule-bearing vesicles associated with slime-body formation in differentiating cells of bean root tips. PMID- 17749105 TI - Repetition and retrieval from memory. PMID- 17749107 TI - Metagons for kappa? PMID- 17749106 TI - Mixed function oxidase reactions in biological oxidations: human placenta. PMID- 17749108 TI - Fusion of SV40 Tumor Cells and Indicator Cells. PMID- 17749109 TI - Studies on the mode of action of vitamin k. PMID- 17749111 TI - Control systems in insect development. PMID- 17749110 TI - Neuron correlates of motivational processes. PMID- 17749112 TI - Experiments with charged quantized vortex rings in superfluid liquid helium. PMID- 17749113 TI - Solar abundance of lead. PMID- 17749114 TI - Quantization of circulation and torque in superfluid helium. PMID- 17749115 TI - Life history studies of physoderma (phycomycetes, chytridiales). PMID- 17749116 TI - Force and momentum for magnetized bodies. PMID- 17749117 TI - Self-administration of psychoactive drugs by the monkey: a measure of psychological dependence. PMID- 17749118 TI - Input-output relations of the systems responsible for a reflex behavior. PMID- 17749119 TI - Acquisition of sensory capabilities. PMID- 17749120 TI - A structural gene for trehalase in neurospora. PMID- 17749121 TI - In situ studies on nitrogen fixation with the acetylene reduction technique. PMID- 17749122 TI - Prolongation of life in mice with established friend virus leukemia by inoculation with sendai virus, interferon, or statolon. PMID- 17749123 TI - Glycolysis, respiration, and enzyme alterations in rat liver neoplasia. PMID- 17749125 TI - Significance of sialic Acid in the temperature-dependent property of cryoglobulins. PMID- 17749124 TI - Test for de novo Synthesis of Enzymes. PMID- 17749126 TI - Determination of the number of active ribosomes in muscle: effect of diabetes and insulin. PMID- 17749128 TI - New york botanical garden-research and education. PMID- 17749127 TI - Novel reaction of a nitro sugar with methanol. PMID- 17749129 TI - THE CONTINUOUS ADVANCE OF ELECTROCHEMISTRY. PMID- 17749130 TI - DISTRIBUTION OF INDIAN TRIBES IN THE SOUTHERN SIERRA AND ADJACENT PARTS OF THE SAN JOAQUIN VALLEY, CALIFORNIA. PMID- 17749131 TI - 'VEGETABLE BALLS.'. PMID- 17749132 TI - THE BLACKENING OF TEETH IN THE ORIENT. PMID- 17749133 TI - NAMATOGAeAN OR EPIGAeAN? PMID- 17749134 TI - THE MECHANISM OF THE MONT PELEE SPINE. PMID- 17749135 TI - A SUGGESTIVE RELATION BETWEEN THE GRAVITATIONAL CONSTANT AND THE CONSTANTS OF THE ETHER. PMID- 17749136 TI - THE ROYAL COMMISSION ON TUBERCULOSIS. PMID- 17749137 TI - THE INTERNATIONAL ASSOCIATION OF ACADEMIES. PMID- 17749138 TI - METHODS OF SECURING BETTER COOPERATION BETWEEN GOVERNMENT AND LABORATORY ZOOLOGISTS IN THE SOLUTION OF PROBLEMS OF GENERAL OR NATIONAL IMPORTANCE. PMID- 17749140 TI - WALTER GOULD DAVIS. PMID- 17749139 TI - MEDICINE, A DETERMINING FACTOR IN WAR. PMID- 17749141 TI - METCALF AND BELL UPON SALPIDAe. PMID- 17749143 TI - A QUICK METHOD OF ELIMINATING SEEDBORNE ORGANISMS OF GRAIN. PMID- 17749144 TI - VARIATIONS IN THE ELECTRICAL POTENTIAL OF THE EARTH. PMID- 17749142 TI - "WORKING UP" IN A SWING. PMID- 17749145 TI - THE BUFFALO MEETING OF THE AMERICAN CHEMICAL SOCIETY. IV. PMID- 17749146 TI - ORGANIZATION OF AMERICAN SCIENTISTS FOR THE WAR. PMID- 17749147 TI - HENRY SEELY WHITE 1861-1943. PMID- 17749148 TI - ARTHUR TRAUTWEIN HENRICI 1889-1943. PMID- 17749149 TI - VITAMIN D PATENTS. PMID- 17749150 TI - RESEARCH IN THE UNITED STATES. PMID- 17749151 TI - THE NATIONAL METAL CONGRESS. PMID- 17749152 TI - THE NEW DIRECTOR OF THE U. S. GEOLOGICAL SURVEY. PMID- 17749153 TI - CIRQUES, HANGING VALLEYS AND HIGHLEVEL BENCHES IN GLACIER NATIONAL PARK. PMID- 17749154 TI - GRAZING VERSUS MAPLE SYRUP. PMID- 17749155 TI - SCIENCE AND SOCIETY. PMID- 17749156 TI - THE MERITS OF ABSTRACTING JOURNALS. PMID- 17749157 TI - INTERFERENCE OF INACTIVE VIRUS WITH THE PROPAGATION OF VIRUS OF INFLUENZA. PMID- 17749158 TI - DIFFERENTIAL INHIBITION BETWEEN NORMAL AND TUMOR (CROWN GALL) TISSUE IN BEET ROOTS. PMID- 17749159 TI - THE EFFECT OF CASTRATION AND TESTOSTERONE PROPIONATE ON d-AMINO ACID OXIDASE ACTIVITY IN THE MOUSE. PMID- 17749161 TI - A NYLON BLOOD AND PLASMA FILTER. PMID- 17749160 TI - A SENSITIVE COLOR REACTION FOR THE DETECTION OF URACIL AND CYTOSINE. AB - (1) Uracil and cytosine are both transformed quantitatively into 5,5 dichloroxyhydrouracil by interaction with superoxol and concentrated hydrochloric acid. (2) This 5,5-dichloroxyhydrouracil reacts with barium hydroxide immediately at ordinary temperature giving the purple colored barium salt of dialuric acid. (3) Both uracil and cytosine can be detected successfully in minute quantities by application of the technique discussed in this paper. PMID- 17749162 TI - The Isotope Distribution Program. PMID- 17749163 TI - Suggested Principles of "Social Physics". PMID- 17749164 TI - Calcium and Growth in Aging and Cancer. PMID- 17749166 TI - Atherosclerosis and Alimentary Hyperlipemia. PMID- 17749165 TI - Coproantibody Excretion During Enteric Infections. PMID- 17749167 TI - Penicillin Types Produced by P. Chrysogenum Q-176. PMID- 17749168 TI - Use of Trisodium Phosphate in Microscopical Technic. PMID- 17749169 TI - THE ASTRONOMICAL AND ASTROPHYSICAL SOCIETY OF AMERICA I. PMID- 17749170 TI - SECTION I--SOCIAL AND ECONOMIC SCIENCE. PMID- 17749171 TI - THE ANTHROPOLOGICAL EXHIBITS AT THE AMERICAN MUSEUM OF NATURAL HISTORY. PMID- 17749172 TI - RADIUM IN BIOLOGICAL RESEARCH. PMID- 17749173 TI - THE FORMATION OF LAKE SUPERIOR COPPER. PMID- 17749174 TI - ELEMENTARY SPECIES AND HYBRIDS OF BURSA. PMID- 17749175 TI - NEW PROCESSES OF TAKING IMPRESSIONS OF NATURAL MOLDS OF FOSSILS. PMID- 17749177 TI - THE GEOLOGICAL SURVEY AT JAMESTOWN. PMID- 17749176 TI - PIERRE EUGENE MARCELLIN BERTHELOT. PMID- 17749178 TI - RESEARCH FELLOWSHIPS IN ENGINEERING AVAILABLE AT THE UNIVERSITY OF ILLINOIS. PMID- 17749179 TI - THE CARNEGIE INSTITUTE. PMID- 17749180 TI - SOLAR SYSTEM EXPLORATION: A More Cautious NASA Sets Plans for Mars. AB - Twice burned by mission failures last year, NASA managers last week unveiled a new 15-year blueprint for Mars exploration. The revamped strategy allows for doing more science, but at a slower pace, while delaying a sample return until well into the next decade. PMID- 17749181 TI - MATERIALS SCIENCE: Long-Wavelength Lasers Sniff Out New Uses. AB - Just a few weeks after two physicists won the Nobel Prize for figuring out how to make lasers out of semiconductors, researchers announced that they have made those lasers much more useful. A new technique permits the lasers to shine light in regions of the infrared spectrum previously inaccessible to similar devices. The advance may open the door to cheap devices to sniff explosives and other robotic sensors. PMID- 17749182 TI - SAVING KYOTO: Can the Kyoto Climate Treaty Be Saved From Itself? AB - The climate treaty being hammered out this month at The Hague may be doomed to failure, as numerous observers say the United States simply won't ratify any treaty that requires such wrenching reductions in carbon emissions, and if the United States bails out, the protocol is in very deep trouble. Some policy analysts think that by tweaking the rules, the United States could eventually sign on, but if they are tweaked too much, other countries may balk. The key, some say, will be keeping the treaty going now and rethinking its controversial goals later. PMID- 17749183 TI - SAVING KYOTO: A Well-Intentioned Cleanup Gets Mixed Reviews. AB - By publishing an alternative, and decidedly upbeat, scenario for how greenhouse warming might play out in the next half-century, the director of NASA's Goddard Institute for Space Studies in New York City hoped to open new prospects for attacking the problem. Instead, he got a lot of grief. PMID- 17749184 TI - HIGH-ENERGY ASTROPHYSICS: Gamma Ray Bursts May Pack a One-Two Punch. AB - Most astrophysicists puzzling over what causes gamma ray bursts--short, intense explosions of high-energy photons that occur deep in space--now agree that the answer is a hypernova, the blast of energy released when a supermassive star collapses into a black hole. Two papers in this issue of Science (pp. 953 and 955), reporting on new x-ray observations of two gamma ray bursts, argue that the hypernova model tells only half of the story. On its way to becoming a black hole, the authors propose, the supermassive star actually collapses twice. PMID- 17749185 TI - HIGH-ENERGY ASTROPHYSICS: X-ray Satellites Seek Clues to Bursts. AB - Last month the High Energy Transient Explorer 2, the first satellite dedicated to spotting gamma ray bursts, rocketed successfully into orbit, bolstering a handful of x-ray satellites whose instruments are trained on the mysterious explosions. But some researchers say setbacks to the fleet have left unfortunate gaps in coverage. PMID- 17749186 TI - Clarifying the SF5CF3 Record. PMID- 17749188 TI - Secret to marital bliss? PMID- 17749189 TI - ESSAYS ON SCIENCE AND SOCIETY: Polygraph Testing and the DOE National Laboratories. AB - A new security policy that mandates polygraph testing as a security measure at U.S. national laboratories has spurred controversy, which is explored in this essay. Congress imposed the requirement last year in response to security failures at the labs. But opponents challenge the scientific validity of the polygraph, and argue that it could tend to undermine the vitality of the labs that it is intended to protect. PMID- 17749187 TI - No mercy. PMID- 17749190 TI - ASTROPHYSICS: Signs of Extreme Gravity. AB - Neutron stars are among the densest objects in the universe, and observations of processes in their vicinity may provide insights into conditions of extreme gravity. Morsink highlights recent observations with the Rossi X-ray Timing Explorer satellite, which are difficult to explain with existing theories. PMID- 17749192 TI - IS THERE ANY DISTINCTION BETWEEN SEXUAL REPRODUCTION AND ASEXUAL REPRODUCTION. PMID- 17749191 TI - THE MAMMALIAN FAUNA OF THE SANTA CRUZ BEDS OF PATAGONIA. PMID- 17749193 TI - STUDY OF THE CORRELATION OF THE HUMAN SKULL. PMID- 17749194 TI - AMERICAN ORNITHOLOGISTS' UNION. PMID- 17749195 TI - THE WELSBACH LIGHT. PMID- 17749197 TI - THE ROYAL SOCIETY. PMID- 17749196 TI - UNIVERSITY REGISTRATION STATISTICS. PMID- 17749198 TI - THE HARTMAN ANTHROPOLOGICAL AND ARCHEOLOGICAL COLLECTION. PMID- 17749199 TI - THE GROWTH OF CITIES. PMID- 17749200 TI - HARBEN LECTURES ON THE PLAGUE. PMID- 17749201 TI - A Fossil-collecting Campaign in New Mexico. PMID- 17749202 TI - Absence of Sickling Phenomenon of the Red Blood Corpuscle Among Brazilian Indians. PMID- 17749203 TI - Nutritional Requirements of the Rat for Reproduction and Lactation. PMID- 17749204 TI - The Spinal Anaesthetic Effects of Ephedrine Sulfate: A Preliminary Report. PMID- 17749205 TI - Fluorescein as an Indicator of Antihistaminic Activity: Inhibition of Histamine induced Fluorescence in the Skin of Human Subjects. PMID- 17749206 TI - Effect of Hormone on Root Formation in Artocarpus communis. PMID- 17749207 TI - Stability of Solutions of Pure Ascorbic Acid and of Dehydroascorbic Acid. PMID- 17749208 TI - The Inhibition of Virus Increase by Malachite Green. PMID- 17749209 TI - Assay of Bacitracin in Body Fluids. PMID- 17749210 TI - An Extension of the Isotope Dilution Method. PMID- 17749211 TI - An Apparatus to Facilitate Intravenous Injections in the Mouse. PMID- 17749213 TI - "Cancer Virus" Feared. PMID- 17749212 TI - A Simple Self-leveling Drinking Well for Laboratory Animals. PMID- 17749214 TI - Letter to the Editor. PMID- 17749215 TI - Galileo: Falsified Record. PMID- 17749216 TI - Assumption. PMID- 17749217 TI - Air Pollution and the Decay of Monuments. PMID- 17749218 TI - English Ivy. PMID- 17749219 TI - Economic Benefits from Oceanographic Research. PMID- 17749220 TI - Chemistry of Isotopes: Isotope chemistry has opened new areas of chemical physics, geochemistry, and molecular biology. AB - With the exception of the field of chemical kinetics, a brief survey has been presented of the principles of isotope chemistry and their utility in the ever unfolding panorama of scientific research. We have come a long way since Soddy and Fajans arrived at the concept of chemical twins-isotopes. There are still places to go. PMID- 17749221 TI - Galileo's Discoveries in Dynamics: He left a mathematical stamp on nature still felt by physicists and natural philosophers. PMID- 17749222 TI - Budget: Total Funds for R&D Rise Modestly to 15.4 Billion; Research Gets Most of Increase. PMID- 17749223 TI - Elliott Committee Staff Receives 2-Month Stay To Prepare Report. PMID- 17749224 TI - Mohole: Drilling Site in Pacific Favored as Time Nears to Award Construction Contract for Vessel. PMID- 17749226 TI - Physicists and Earth Scientists Issue Studies of Opportunities, Needs in Their Research Fields. PMID- 17749225 TI - Title VI: Universities, Others Affected by Federal Moves To End Discrimination by Aid Recipients. PMID- 17749227 TI - Sulfur: Role in Genesis of Petroleum. AB - Sulfur reacts readily with cholesterol at 150 degrees C, and the product of the reaction contains aromatic hydrocarbons, some with a benzene, some a naphthalene, and some a phenanthrene ring system as part of the molecule. The reaction of farnesol with sulfur takes place at 135 degrees C. Cadalene (1,6-dimethyl-4 isopropylnaphthalene) is one of the products of the reaction. These reactions at relatively low temperatures support the proposition that a thermal reaction of sulfur with terpenoids and steroids plays a part in the genesis of petroleum. PMID- 17749228 TI - Carbonate in Hydroxylapatite. AB - Unit cell dimensions of hydroxylapatite synthesized hydrothermally are a(0) = 9.42(6) A and c(0) = 6.88(5) A, whereas carbonate apatite (2.29 CO(2)) gave a(0) = 9.43(6) A and c(0) = 6.88(5) A. A deficiency of both calcium and phosphorus in the carbonate apatite suggests a coupled substitution of hydronium and carbonate ions in the structure. PMID- 17749229 TI - Lead Isotopes in Gasoline and Aerosols of Los Angeles Basin, California. AB - The isotopic composition of lead isolated from antiknock gasolines and the aerosols of the Los Angeles basin was determined. The lead isotopic composition of the aerosols was similar to that of rural snow. The high concentration of lead in water of precipitation and that of the surface of the sea can be attributed to automobile exhausts. PMID- 17749230 TI - Thermal Neutron Activation: Measurement of Cross Section for Manganese-53. AB - The product of the thermal neutron activation cross section and half-life for manganese-53 is (350 +/- 100) x 10(6) barn-years. If a value of 2 x 10(6) years is assumed for the half-life of manganese-53, then the cross section is 170 barns. This large cross section affords much greater sensitivity for the determination of manganese-53. PMID- 17749232 TI - Space Simulation: Man-Rated Testing and Vacuum Generation. PMID- 17749231 TI - Antimicrobial Agents and Chemotherapy. PMID- 17749233 TI - Analytical Chemistry in Nuclear Technology. PMID- 17749234 TI - Unsettling Side to Settling Technical Issues. PMID- 17749235 TI - Basic Research in Industry: A count of scientific publications suggests the extent of U.S. industry's effort in basic research. PMID- 17749236 TI - News of Science. PMID- 17749237 TI - Paper Coal in Indiana. AB - The foliated, papery texture of the upper third of an 18-inch coal seam in a strip mine near Rockville, Indiana, is attributable to matted plant cuticle. The cuticles of pinnules, pinnae, and rachides resemble Sphenopteris bradfordii Arnold and thus differ from the lycopsid stem cuticles of the Russian paper coal. PMID- 17749240 TI - Loyalty Oath. PMID- 17749239 TI - What Is a Profession? PMID- 17749241 TI - Scientists Need a Group Opinion. PMID- 17749243 TI - SCIENCE NEWS. PMID- 17749242 TI - Shutoff Pulse Illusion. PMID- 17749244 TI - DOCTOR WILLIAM H. WELCH. 1850-1934. PMID- 17749245 TI - EXILES IN BRITISH SANCTUARY. PMID- 17749246 TI - INSECT TRANSMISSION EXPERIMENTS WITH HERPES-ENCEPHALITIS VIRUS. PMID- 17749247 TI - SKIN TEMPERATURE REACTIONS FOLLOWING REMOVAL OF THE LEFT CEREBRAL HEMISPHERE. PMID- 17749248 TI - AN ENCYCLOPEDIA OF CHEMICAL REACTIONS. PMID- 17749249 TI - THE MISSOURI ACADEMY OF SCIENCE. PMID- 17749250 TI - THE COST OF GERMAN PUBLICATIONS. PMID- 17749252 TI - THE IOWA ACADEMY OF SCIENCE. PMID- 17749251 TI - THE PARSELENIC CIRCLE. PMID- 17749253 TI - AVIAN MALARIAL INFECTIONS AS CLASSROOM MATERIAL. PMID- 17749254 TI - THE PENNSYLVANIA ACADEMY OF SCIENCE. PMID- 17749255 TI - THE KANSAS ACADEMY OF SCIENCE. PMID- 17749256 TI - DEVICE FOR CONSTANT FLOW OF LIQUIDS. PMID- 17749258 TI - POSSIBLE CHEMICAL NATURE OF TOBACCO MOSAIC VIRUS. PMID- 17749257 TI - LATENT PSITTACOSIS AND SALMONELLA PSITTACOSIS INFECTION IN SOUTH AMERICAN PARROTLETS AND CONURES. PMID- 17749259 TI - SOIL MINERALS AS A CHECK ON THE LOCATION OF THE WISCONSIN-ILLINOIAN DRIFT BOUNDARY IN NORTH CENTRAL OHIO. PMID- 17749260 TI - Genes and Nucleoproteins in the Synthesis of Enzymes. PMID- 17749261 TI - Enoch Karrer 1887-1946. PMID- 17749262 TI - Bernice Maclean Shapiro 1903-1946. PMID- 17749263 TI - Philippe Lasseur 1882-1946. PMID- 17749264 TI - A Possible Avian Analogue of the Scrotum. PMID- 17749265 TI - Comparison of Some New Analgesic Compounds. PMID- 17749266 TI - Science Exhibition. PMID- 17749267 TI - Photographic Measurement of Radiation Quality and Quantity. PMID- 17749268 TI - The Use of Unsaturated Polyester Resins for Embedding Biological Material. PMID- 17749269 TI - A New Spectrophotometric Method for the Determination of Vitamin A. PMID- 17749270 TI - Reduction of Excess Acetylcholine in the Serum of Pernicious Anemia Patients by Treatment With Pteroyl Glutamic Acid, Liver Extract, or Ventriculin. PMID- 17749271 TI - The Possible Role of the Guppy, Lebistes reticulatus, on the Biological Control of Schistosomiasis mansoni. PMID- 17749272 TI - Myosin and Adenosinetriphosphatase in Muscular Activity. PMID- 17749273 TI - Life Insurance Medical Research Fund Grants. PMID- 17749274 TI - On Virus Nomenclature. PMID- 17749275 TI - RESEMBLANCES AND DIFFERENCES AMONG AMERICAN UNIVERSITIES. PMID- 17749276 TI - THE RELATIONS OF MUSEUMS TO EXPERTS AND SYSTEMATISTS WHO ARE ENGAGED IN WORKING UP AND NAMING COLLECTIONS. PMID- 17749277 TI - A LECTURE EXPERIMENT IN HYDRAULICS. PMID- 17749278 TI - A BLAZING BEACH. PMID- 17749279 TI - THE FIRST DISCOVERY OF FOSSIL SEALS IN AMERICA. PMID- 17749280 TI - 'THE COLLAPSE OF EVOLUTION.'. PMID- 17749282 TI - NOTE ON THE FUNCTIONS OF THE FINS OF FISHES. PMID- 17749281 TI - A NEW MIOCENE ARTIODACTYL. PMID- 17749283 TI - LABORATORY EXPERIMENTS WITH CS2 TO DETERMINE THE LEAST AMOUNT OF GAS AND THE LEAST TIME REQUIRED TO KILL CERTAIN INSECT REPRESENTATIVES OF VARIOUS FAMILIES. PMID- 17749285 TI - BOTANICAL NOTES. PMID- 17749284 TI - A NOTE ON THE CALCULATION OF CERTAIN PROBABLE ERRORS. PMID- 17749286 TI - THE AMERICAN CHEMICAL SOCIETY. PMID- 17749287 TI - RAILWAY RATES FOR THE NEW ORLEANS MEETING. PMID- 17749288 TI - Letter to the editor. PMID- 17749289 TI - The albatross award. PMID- 17749290 TI - Appointments to working government councils. PMID- 17749291 TI - Marital status and mobility. PMID- 17749293 TI - Pesticide regulation. PMID- 17749292 TI - Knowledge factory. PMID- 17749294 TI - Letter to the editor. PMID- 17749296 TI - A visit to bulgaria. PMID- 17749295 TI - Parapsychology. PMID- 17749297 TI - A sino-american soybean research institute. PMID- 17749298 TI - The Lunar Laser Ranging Experiment: Accurate ranges have given a large improvement in the lunar orbit and new selenophysical information. AB - The lunar ranging measurements now being made at the McDonald Observatory have an accuracy of 1 nsec in round-trip travel time. This corresponds to 15 cm in the one-way distance. The use of lasers with pulse-lengths of less than 1 nsec is expected to give an accuracy of 2 to 3 cm in the next few years. A new station is under construction in Hawaii, and additional stations in other countries are either in operation or under development. It is hoped that these stations will form the basis for a worldwide network to determine polar motion and earth rotation on a regular basis, and will assist in providing information about movement of the tectonic plates making up the earth's surface. Several mobile lunar ranging stations with telescopes having diameters of 1.0 m or less could, in the future, greatly extend the information obtainable about motions within and between the tectonic plates. The data obtained so far by the McDonald Observatory have been used to generate a new lunar ephemeris based on direct numerical integration of the equations of motion for the moon and planets. With this ephemeris, the range to the three Apollo retro-reflectors can be fit to an accuracy of 5 m by adjusting the differences in moments of inertia of the moon about its principal axes, the selenocentric coordinates of the reflectors, and the McDonald longitude. The accuracy of fitting the results is limited currently by errors of the order of an arc second in the angular orientation of the moon, as derived from the best available theory of how the moon rotates in response to the torques acting on it. Both a new calculation of the moon's orientation as a function of time based on direct numerical integration of the torque equations and a new analytic theory of the moon's orientation are expected to be available soon, and to improve considerably the accuracy of fitting the data. The accuracy already achieved routinely in lunar laser ranging represents a hundredfold improvement over any previously available knowledge of the distance to points on the lunar surface. Already, extremely complex structure has been observed in the lunar rotation and significant improvement has been achieved in our knowledge of lunar orbit. The selenocentric coordinates of the retroreflectors give improved reference points for use in lunar mapping, and new information on the lunar mass distribution has been obtained. Beyond the applications discussed in this article, however, the history of science shows many cases of previously unknown, phenomena discovered as a consequence of major improvements in the accuracy of measurements. It will be interesting to see whether this once again proves the case as we acquire an extended series of lunar distance observations with decimetric and then centimetric accuracy. PMID- 17749299 TI - Picosecond kinetics of reaction centers containing bacteriochlorophyll. PMID- 17749300 TI - Millikelvin Temperatures Measured with a Noise Thermometer: Brownian motion in electrical circuits has been used to measure temperatures as low as 2 millikelvins. AB - We find that the current-sensitive noise thermometer is a satisfactory sensor of absolute temperature down to 2 mK and possibly below. Its field of application is primarily to magnetically and electrically quiet situations where accuracy is important and high precision is not required. For example the noise thermometer is an ideal instrument for calibrating a secondary thermometer, such as a pressure thermometer, whose calibration can readily and accurately be transferred from one laboratory to another. Further instrumental development for millidegree applications seems unnecessary at present. Rather the major problems in millikelvin noise thermometry that require attention in the immediate future involve establishing thermal contact to the thermometer and reducing its thermal response time. PMID- 17749301 TI - Meteorological Doppler radar. PMID- 17749302 TI - Electric power research institute: a new formula for industry r&d. PMID- 17749303 TI - Europe joins in shuttle project. PMID- 17749304 TI - Training grants: tied up in congress with ethics bills. PMID- 17749305 TI - Water projects: how to erase the "pork barrel" image? PMID- 17749306 TI - Telecommunications: u.s. Applications fall short. PMID- 17749307 TI - Volcanic gases: hydrogen burning at kilauea volcano, hawaii. AB - Spectroscopic evidence for hydrogen burning in air was obtained at Kilauea Volcano. The abundance of hydrogen required to support combustion is consistent with that predicted for gases in equilibrium with typical Hawaiian tholeiitic basalt. PMID- 17749308 TI - Ground-based thermal infrared surveys as an aid in predicting volcanic eruptions in the cascade range. AB - Detailed, ground-based thermal surveys of selected slopes of Mt. Rainier and Mt. Lassen have provided quantitative data for the construction of thermal contour maps of portions of the flanks of these volcanoes. Preliminary surveys substantiate the existence of one suspected thermal anomaly on Mt. Rainier. PMID- 17749310 TI - Amazon warfare. PMID- 17749309 TI - Chondrites: initial strontium-87/strontium-86 ratios and the early history of the solar system. AB - A sodium-poor, calcium-rich inclusion in the carbonaceous chondrite Allende had a (87)Sr/(86)Sr ratio at the time of its formation of 0.69880, as low a value as that found in any other meteorite. The higher (87)Sr/(86)Sr ratios found in ordinary chondrites indicate that their formation or isotopic equilibration occurred tens of millions of years later. PMID- 17749311 TI - Erratum. AB - In the report "Aborginal Indian residence patterns preserved in censuses and allotments" by John H. Moore (11 Jan., p. 201), Table 1 was inadvertently omitted: Table 1. Distances from mothers' to married children's allotments for first-generation descendents of Sand Creek family heads. [See table in the PDF file]. PMID- 17749312 TI - The eagle and the bear. PMID- 17749313 TI - Accreting neutron stars, black holes, and degenerate dwarf stars. AB - During the past 8 years, extended temporal and broadband spectroscopic studies carried out by x-ray astronomical satellites have led to the identification of specific compact x-ray sources as accreting neutron stars, black holes, and degenerate dwarf stars in close binary systems. Such sources provide a unique opportunity to study matter under extreme conditions not accessible in the terrestrial laboratory. Quantitative theoretical models have been developed which demonstrate that detailed studies of these sources will lead to a greatly increased understanding of dense and superdense hadron matter, hadron superfluidity, high-temperature plasma in superstrong magnetic fields, and physical processes in strong gravitational fields. Through a combination of theory and observation such studies will make possible the determination of the mass, radius, magnetic field, and structure of neutron stars and degenerate dwarf stars and the identification of further candidate black holes, and will contribute appreciably to our understanding of the physics of accretion by compact astronomical objects. PMID- 17749314 TI - Edison and the pure science ideal in 19th-century america. AB - Between 1878 and 1882, key members of the American scientific community played an important role in Thomas A. Edison's work on electric lighting. Impressed by his abilities, these scientists came to regard Edison as a peer and led him to see himself as a scientific man. But Edison's high standing among scientists and the American public and his professed self-image as a scientist provoked America's noted experimental physicist, Henry A. Rowland, to make a "Plea for pure science" before the American Association for the Advancement of Science in 1883. PMID- 17749315 TI - Science gains slightly in 1981 budget. PMID- 17749316 TI - Fusion energy in our time. PMID- 17749318 TI - No "humane" executions, Boston doctors say. PMID- 17749317 TI - A New Call for Abolishing the NRC. PMID- 17749319 TI - U. S. Scientists protest punishment of sakharov. PMID- 17749320 TI - Explorer: can oil and science mix? PMID- 17749321 TI - General relativity since einstein. PMID- 17749322 TI - Primate behavior. PMID- 17749323 TI - Zooarcheology. PMID- 17749324 TI - Developmental psychology. PMID- 17749325 TI - Nitric oxide in seawater. AB - Nitrite photolysis at natural light intensities and normal nitrite concentrations in seawater produced detectable concentrations of nitric oxide, which was consumed rapidly by a dark chemical reaction in the laboratory. Nitric oxide was also detected in situ in nitrite-rich surface waters of the central equatorial Pacific, where it formed in daylight and disappeared rapidly at sunset. The formation and rapid cycling of nitric oxide implies the presence of other free radicals in seawater, perhaps as intermediates in ongoing autoxidation processes. The central equatorial Pacific is a nitric oxide source to the atmosphere. PMID- 17749326 TI - Lead isotope identification of sources of galena from some prehistoric Indian sites in ontario, Canada. AB - Lead isotopic compositions of 12 galenas from five late Archaic-initial Woodland grave and habitation sites in southern Ontario have made it possible to determine the "most likely" source areas for the galenas. For one of the oldest sites (Finlan), the most likely source is in the southwestern Upper Mississippi Valley (Wisconsin-Illinois-Iowa) mineral district. The seven Finlan galenas exhibit a range of isotopic ratios; three of the largest specimens have substantial isotopic variations (up to 1.8 percent in the ratio of lead-207 to lead-206) on a scale of a few centimeters. This suggests that the lead isotopic zoning ascribed to the Upper Mississippi Valley area is not sufficiently well defined to enable us to determine if all the Finlan samples were derived from a single mineral deposit. Galenas from the other sites (Constance Bay, Hind, Bruce Boyd, and Picton) most probably originated in the southeastern Ontario-northwestern New York area. Isotopic differences among the Constance Bay, Hind, and Bruce Boyd galenas, on the one hand, and the Picton galena, on the other, suggest that at least two distinct sources in that region were exploited. PMID- 17749327 TI - Benjamin Franklin and Timothy Folger's First Printed Chart of the Gulf Stream. AB - A print of the Benjamin Franklin and Timothy Folger 1769-1770 chart of the Gulf Stream, all copies of which have been "lost" for nearly 200 years, was found in the Bibliotheque Nationale in Paris. This is the first chart of the Gulf Stream and continues today to be a good summary of its strength, course, and breadth. PMID- 17749328 TI - Sound Playback Experiments with Southern Right Whales (Eubalaena australis). AB - A variety of sound recordings were played to southern right whales. Whales approached the loudspeaker and made frequent sounds in response to recordings of other southern right whales, but swam away and made relatively few sounds in response to playbacks of water noise, 200-hertz tones, and humpback whale sounds. Thus it appears that southern right whales can differentiate between con-specific sounds and other sounds. PMID- 17749330 TI - PRODUCTS and MATERIALS. PMID- 17749329 TI - Genetic variation in social mammals: the marmot model. AB - The social substructure and the distribution of genetic variation among colonies of yellow-bellied marmots, when analyzed as an evolutionary system, suggests that this substructure enhances the intercolony variance and retards the fixation of genetic variation. This result supports a traditional theory of gradual evolution rather than recent theories suggesting accelerated evolution in social mammals. PMID- 17749332 TI - QUA VADIMUS? PMID- 17749331 TI - SCIENCE NEWS. PMID- 17749333 TI - SO-CALLED VOLCANIC EARTHQUAKES. PMID- 17749335 TI - WILLIAM E. SAFFORD. PMID- 17749334 TI - NEW YORK CITY AS A FIELD FOR EARTHQUAKE STUDY. PMID- 17749336 TI - MAPS FOR THE INTERNATIONAL GEOLOGICAL CONGRESS AT MADRID. PMID- 17749337 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17749338 TI - THE AUTOMOBILE AND WILD LIFE. PMID- 17749339 TI - SCIENCE SERVICE AND THE LOCATION OF EARTHQUAKE EPICENTERS. PMID- 17749340 TI - ON EINSTEIN'S THEORY OF RELATIVITY. PMID- 17749341 TI - IODINE IN THYROID DEFICIENCY. PMID- 17749343 TI - FLUORIDES VS. FLUOSILICATES AS INSECTICIDES. PMID- 17749342 TI - ON THE EQUILIBRIUM BETWEEN THE ENAMEL OF THE TEETH AND THE SALIVA. PMID- 17749344 TI - THE TULSA MEETING OF THE AMERICAN CHEMICAL SOCIETY. PMID- 17749345 TI - THE SUMMERS WORK AT THE WOODS HOLE LABORATORY OF THE BUREAU OF FISHERIES (FORMJER U. S. FISH COMMISSION). PMID- 17749346 TI - SOCIETY OF THE VERTEBRATE PALEONTOLOGISTS OF AMERICA. PMID- 17749347 TI - THE MEMBERSHIP OF THE AMERICAN ASSOCIATION. PMID- 17749348 TI - CONIVOCATION WEEK. PMID- 17749350 TI - THE TOURMALINE LOCALITIES OF SOUTHERN CALIFORNIA. PMID- 17749349 TI - THE CLEMSON COLLEGE SCIENCE CLUB. PMID- 17749352 TI - EXPERIMENTS IN FLYING. PMID- 17749351 TI - A NOTE ON RHIZOCTONIA. PMID- 17749353 TI - NOTES ON INORGANIC CHEMIASTRY. PMID- 17749354 TI - THE SAUROPODA. PMID- 17749356 TI - THE SMITHSONIAN INSTITUTION. PMID- 17749355 TI - THE MILWAUKEE MUSEUM. PMID- 17749357 TI - SCIENCE NEWS. PMID- 17749358 TI - SCIENCE SERVICE CONFERENCE. PMID- 17749359 TI - THE NEW HARVARD BIOLOGICAL LABORATORIES. PMID- 17749360 TI - OBITUARY. PMID- 17749361 TI - NOTE ON PREMATURE FLOWERING IN GRAPEFRUIT FROM X-RAYED SEEDS. PMID- 17749363 TI - A PROPOSED WORKING ABSTRACT OF THE LITERATURE OF CHEMISTRY. PMID- 17749362 TI - NECROBIOTIC RAYS. PMID- 17749364 TI - PROBABILITY OF A MAGNETIC STORM DURING THE SOLAR ECLIPSE OF AUGUST 31, 1932. PMID- 17749366 TI - A PIPETTE FOR THE DILUTION COUNTING OF HOOKWORM EGGS. PMID- 17749365 TI - MERCURY VAPOR PUMPS FOR VACUUM DISTILLATIONS. PMID- 17749367 TI - THE VALIDITY OF MEASURING EYE MOVEMENTS BY DIRECT OBSERVATION. PMID- 17749369 TI - Everybody Talks about the Weather, but.. PMID- 17749368 TI - Misinterpretation. PMID- 17749370 TI - Relevance of research to students. PMID- 17749371 TI - Electroluminescence seen in 1907. PMID- 17749372 TI - The use of arid lands. PMID- 17749373 TI - High-temperature batteries. PMID- 17749374 TI - CBW: Pressures for Control Build in Congress, International Groups. PMID- 17749375 TI - London school of economics: end of a year of upheaval. PMID- 17749377 TI - Convergence and strain waves caused by a submerged turbulent disturbance in stratified fluids. AB - Short bursts of submerged turbulent mixing in stratified water (every-where denser below than above) is shown to cause waves of surface convergence, divergence, and strain. Quantitative data are given for four experiments. PMID- 17749376 TI - Airglow and star photographs in the daytime from a rocket. AB - Photographs of the constellation Cygnus taken in the daytime from altitudes above 100 kilometers indicate that the day sky brightness in the wave-length region from 3600 to 7000 angstroms is only slightly brighter than the night sky viewed from the ground. No diffuse cloud of particles was apparent in the vicinity of the rocket payload, but discrete particles must be considered in the design of instruments for rockets and satellites. The resultant data and reports of star sightings from manned spacecraft indicate similar optical environments for both types of vehicles, that is, discrete particles and relatively low levels of background brightness, only slightly brighter than the night sky as an upper limit. PMID- 17749378 TI - Slumping structures caused by organically derived gases in sediments. AB - The interstitial waters of many sediments are saturated with methane derived from the decay of included organic material. Further generation of methane or local pressure reduction resuilts in sediment dilation and loss of sediment stability. The grains of sediment separated by gas behave in toto as an elastic fluid, and typical " slumping structures " result. PMID- 17749379 TI - Peanuts: gibberellin antagonists and genetically controlled differences in growth habit. AB - Treatment of peanuts with gibberellin changed the orientation of lateral branches of runners to that of erect ones, and two growth retardants changed those of the erect type to a more horizontal orientation. Little or no difference was found in amounts of endogenous gibberellin in the two types of plants, but amount of native gibberellic acid antagonists was higher in runner plants. Furthermore, runner plants contained a particular gibberellic acid inhibitor not found in erect plants. Applications of various auxins, antiauxins, and a cytokinin had no effect on tropistic growth of the side branches. PMID- 17749380 TI - Protective Effect of Antilymphocyte Serum on Mice Infected with Plasmodium berghei. AB - Rabbit antiserum to mouse lymphocytes prolonged the survival of mice infected with Plasmodium berghei. Since antilymphocyte serum has a well-defined, potent immunosuppressive effect, the immune response of the host to the parasite actually may contribute to the death of the animal with an acute malarial infection. PMID- 17749381 TI - Radiosensitivity in animals. PMID- 17749382 TI - AAAS-Westinghouse Science Writing Competition for 1969. PMID- 17749383 TI - SCIENCE NEWS. PMID- 17749385 TI - GLOBIGERINA BEDS AS DEPTH INDICATORS IN THE TERTIARY SEDIMENTS OF FIJI. PMID- 17749384 TI - METHODS OF APPROACH IN TEACHING TAXONOMY. PMID- 17749386 TI - THE OCCURRENCE OF CUPULAE ON LATERAL-LINE ORGANS. PMID- 17749387 TI - The Life History of a Poultry Cestode. PMID- 17749388 TI - SULFOCYANATE TREATMENT OF MANGE IN GUINEA PIGS. PMID- 17749389 TI - THE ALCOHOLIC ADMISSIONS TO BELLEVUE HOSPITAL. PMID- 17749390 TI - A NEW TYPE OF ENZYME IN THE INTESTINAL TRACT. PMID- 17749391 TI - A PRECISION APPARATUS FOR MIXING GASES IN VARIOUS PROPORTIONS. PMID- 17749392 TI - THE USE OF POLARIZED LIGHT IN THE SIMULTANEOUS COMPARISON OF RETINALLY AND CORTICALLY FUSED COLORS. PMID- 17749393 TI - AAAS Grants and Prizes. PMID- 17749394 TI - Publications Received. PMID- 17749395 TI - Meetings & Conferences. PMID- 17749397 TI - Methodology and theory at the frontier. PMID- 17749396 TI - The week in Science. PMID- 17749398 TI - Conservation biology: its origins and definition. PMID- 17749399 TI - Conservation biology: its origins and definition. PMID- 17749400 TI - Erratum. AB - In the "NATO International Scientific Exchange Programmes" (31 Jan., p. 577), the item "Cell-free analysis of the functional organization of the cytoplasm" was listed incorrectly. The title should have been "Molecular mechanisms of membrane traffic." The organizer is Dr. Kathryn Howell, American Society for Cell Biology/NATO, 9650 Rockville Pike, Bethesda, MD 20814, USA. The date and place are 9-13 May 1992 and Virginia, USA, respectively. PMID- 17749401 TI - Ig nobel prize: the pogo connection. PMID- 17749402 TI - Synchrotron radiation facilities. PMID- 17749404 TI - Sciencescope. PMID- 17749403 TI - Greenland research projects. PMID- 17749405 TI - A clearinghouse that could get clogged. PMID- 17749406 TI - Piecemeal rescue for soviet science. PMID- 17749407 TI - A profusion of projects. PMID- 17749408 TI - Bush tries trimming r&d pork. PMID- 17749409 TI - Biotech's Chinese Connection. PMID- 17749410 TI - Do NASA Images Create Fantastic Voyages? PMID- 17749411 TI - Red ink at harvard. PMID- 17749412 TI - A voice for bio-engineering. PMID- 17749413 TI - Asbestos Regs to Be Re-examined. PMID- 17749415 TI - Top science jobs lose appea. PMID- 17749414 TI - Precolumbian trees. PMID- 17749416 TI - You Can't Hear the Shape of a Drum. PMID- 17749417 TI - Controlling chemical reactions with laser light. PMID- 17749418 TI - Previewing This Year's FASEB Offerings. PMID- 17749419 TI - Raising tibet. AB - Thermochronologic, sedimentologic, oceanographic, and paleoclimatic studies suggest that rapid uplift and unroofing of southern Tibet began about 20 million years ago and that the present elevation of much of the Tibetan plateau was attained by about 8 million years ago. Hypotheses advanced to explain the tectonic evolution of the India-Asia collision, which began about 40 to 50 million years ago, predict the timing and rates of crustal thickening of the southern margin of Asia. However, these models do not predict the prominently enhanced early Miocene denudation and uplift that are manifested in a variety of geological records. A model involving continental extrusion, development of a crustal-scale thrust ramp of the Main Central Thrust beneath the Gangdese belt, and lithospheric delamination provides a history consistent with these observations. PMID- 17749420 TI - The Inner Core Translational Triplet and the Density Near Earth's Center. AB - Four long records from superconducting gravimeters yield evidence of the triplet of translational oscillations of the solid inner core about its central position. Calculations of core oscillation modes allow identification of the three translational resonances at periods of 3.5820 +/- 0.0008, 3.7677 +/- 0.0006, and 4.015 +/- 0.001 hours by their rotational splitting. Each resonance is defined by approximately 20 successive spectral estimates. A new Earth model brings the computed periods into agreement with observation. It has a central density of 12.960 grams per cubic centimeter, inner core radius of 1221.1 kilometers, and a density jump at the inner core boundary of 0.407 grams per cubic centimeter. PMID- 17749421 TI - The breakup of a meteorite parent body and the delivery of meteorites to Earth. AB - Whether many of the 10,000 meteorites collected in the Antarctic are unlike those failing elsewhere is contentious. The Antarctic H chondrites, one of the major classes of stony meteorites, include a number of individuals with higher induced thermoluminescence peak temperatures than observed among non-Antarctic H chondrites. The proportion of such individuals decreases with the mean terrestrial age of the meteorites at the various ice fields. These H chondrites have cosmic-ray exposure ages of about 8 million years, experienced little cosmic ray shielding, and suffered rapid postmetamorphic cooling. Breakup of the H chondrite parent body, 8 million years ago, may have produced two types of material with different size distributions and thermal histories. The smaller objects reached Earth more rapidly through more rapid orbital evolution. PMID- 17749422 TI - Response of regional seismicity to the static stress change produced by the loma prieta earthquake. AB - The 1989 Loma Prieta, California, earthquake perturbed the static stress field over a large area of central California. The pattern of stress changes on major faults in the region predicted by models of the earthquake's dislocation agrees closely with changes in the regional seismicity rate after the earthquake. The agreement is best for models with low values of the coefficient of friction (0.1 /= 700, and the mass of the unseen companion probably lies close to the upper limit of the range 0.25 M. to 1.0 M.. The secondary cannot be a main sequence star and is probably a degenerate helium dwarf. At the 5.6-kiloparsec distance indicated by the dispersion measure, the magnetic dipole model gives an age of approximately 4 x 104 years, a rate of change of the pulsar period of P approximately 2 nanoseconds per day, and a surface magnetic field strength approximately (1/3) that of the Crab pulsar. The pulsar is fainter than an apparent magnitude V approximately + 26.5 and is at least approximately 80 times fainter than the Crab pulsar in the x-ray band. The companion star should be fainter than V approximately + 30, and a radio supernova remnant may be detectable near the position of the pulsar at a flux level of (1/2) the central nuclear magnetic resonance transition can be employed in high-resolution experiments that involve rapid sample spinning. A continuing stream of advances holds great promise for the use of high-resolution techniques for the characterization of solids by a wide range of nuclides. PMID- 17749873 TI - A Cloudy Forecast for Solar Cells: The U.S. photovoltaic industry, facing rising costs and growing Japanese competition, is looking to Washington for assistance. PMID- 17749874 TI - The Mystery of Florida's Citrus Canker: Scientists haven't seen this bacterial strain before, but it's already led to the destruction of millions of seedlings. PMID- 17749872 TI - Chemical sensing in process analysis. AB - Improvements in process control, which determine production efficiency and product quality, are critically dependent upon on-line process analysis. The technology of the required instrumentation will be substantially expanded by advances in sensing devices. In the future, the hardware will consist of sensor arrays and miniaturized instruments fabricated by microlithography and silicon micromachining. Chemometrics will be extensively used in software to provide error detection, selfcalibration, and correction as well as multivariate data analysis for the determination of anticipated and unanticipated species. A number of examples of monolithically fabricated sensors now exist and more will be forthcoming as the new paradigms and new tools are widely adopted. A trend toward not only on-line but even in-product sensors is becoming discernible. PMID- 17749875 TI - DOD Buys Secure Telephones. PMID- 17749876 TI - Comings and goings. PMID- 17749877 TI - Test-maker sues stanford. PMID- 17749878 TI - Climate Since the Ice Began to Melt: Newly mapped climate changes of the past 18,000 years are being simulated in computer models, helping to point toward causes and to verify the models. PMID- 17749879 TI - Surprise finding with insect globin genes. PMID- 17749880 TI - Femtosecond Laser Annealing of Silicon: The thermal melting and recrystallization processes invoked at slower speeds fail for subpicosecond pulses, a new twist on an old controversy. PMID- 17749882 TI - Earth history: the chemical evolution of the atmosphere and oceans. PMID- 17749881 TI - The standardization of manufacturing: from the american system to mass production, 1800-1932. PMID- 17749883 TI - The sound of music: the science of musical sound. PMID- 17749884 TI - Spread of diadema mass mortality through the Caribbean. AB - Populations of the ecologically important sea urchin Diadema antillarum suffered severe mass mortalities throughout the Caribbean. This mortality was first observed at Panama in January 1983; by January 1984 it had spread to the rest of the Caribbean and to Bermuda. The sequence of mortality events in most areas is consistent with the hypothesis that the causative agent was dispersed by major surface currents over large distances. However, some of the late die-offs in the southeastern Caribbean do not fit this pattern. Several lines of indirect evidence suggest that the phenomenon is due to a water-borne pathogen. If so, this is the most extensive epidemic documented for a marine invertebrate. PMID- 17749885 TI - The jovian nebula: a post-voyager perspective. AB - Voyager 1 carried a diverse collection of magnetospheric probes through the inner Jovian magnetosphere in March 1979. The ensuing data analysis and theoretical investigation provided a comprehensive description of the Jovian nebula, a luminous torus populated with newly released heavy ions drawn from Io's surface. Recent refinements in Earth-based imaging instrumentation are used to extend the Voyager in situ picture in temporal and spatial coverage. An analysis of [SIII] and [SII] optical emissions observed during the Jovian apparitions of 1981 through 1983 reveals three distinct torus components. Regularities have been identified in the ion partitioning and ion densities in the hot outer and inner tori, sharply defined radial structure is found in the plasma near Io, and the relative permanence of the cool inner torus is inferred. An extended cloud of neutral material is required as a source of fresh ions in the nebula. PMID- 17749886 TI - Photocontraction of liquid spiropyran-merocyanine films. AB - Amorphous films of a photochromic spiropyran containing a mesogenic group melt, when exposed to heat together with irradiation, to yield a red fluid. This fluid contains aggregates of merocyanine molecules and exhibits marked contraction under light illumination. The mechanism of the photocontraction is dependent upon a specialized microstructure, which may be termed a "quasi-liquid." PMID- 17749887 TI - Temporal variability of the antarctic circumpolar current observed from satellite altimetry. AB - Sea level measurements by the Seasat altimeter were used to study the temporal variability of the Antarctic Circumpolar Current between July and October 1978. Large-scale zonal coherence in the cross-stream sea level difference was observed, indicating a general increase in the surface geostrophic velocity of the current around the Southern Ocean. The result demonstrates the power of satellite altimetry to monitor the variability of large-scale ocean currents. PMID- 17749889 TI - Impact event at the cretaceous-tertiary boundary: a possible site. PMID- 17749888 TI - Extensive volcanism associated with the separation of australia and antarctica. AB - Alternating hard and soft layers characterize the Gull Rock and Tuit Members of the late Eocene Blanche Point Formation, South Australia. Originally the formation was mainly a mixture of volcanic ash, sponge spicules, and calcareous fossil remains, with hard layers produced later by selective silicification. It resembles Cretaceous sediments from western Europe and the eastern coast of the United States, and in each case it appears that alteration of volcanic ash produced smectite and clinoptilolite with release of silica that subsequently crystallized as opal-CT. The occurrence of similar deposits from New Zealand to as far west as Albany, Western Australia, indicates extensive volcanic activity south of Australia in the late Eocene resulting from rifting and separation from Antarctica. PMID- 17749890 TI - Uncertainty of histologic classification of experimental tumors. PMID- 17749891 TI - This Week in SCIENCE. PMID- 17749892 TI - Accounting for America's Uncounted and Miscounted. PMID- 17749893 TI - Sciencescope. PMID- 17749894 TI - The patent game: raising the ante. PMID- 17749895 TI - Computerizing 28 million files. PMID- 17749896 TI - Can electronic property be protected? PMID- 17749898 TI - Baltimore case--in brief: the scientific results. PMID- 17749897 TI - Baltimore Case--In Brief: OSI Flip-Flops on Storb. PMID- 17749900 TI - British ferrets to hungry. PMID- 17749899 TI - Baltimore case--in brief: scientific community splits. PMID- 17749901 TI - A brighter forecast from kuwait. PMID- 17749903 TI - Better dead in lead. PMID- 17749902 TI - Brotherhood of lions. PMID- 17749904 TI - Shooing the screwworm fly. PMID- 17749905 TI - Essence of a smile. PMID- 17749906 TI - Health care: teens can go it alone. PMID- 17749907 TI - U.S. Eases the Pressure on RU-486. PMID- 17749908 TI - The high side of gravity. PMID- 17749909 TI - Early Bird Threatens Archaeopteryx's Perch. PMID- 17749910 TI - Celestial mechanics on a microscopic scale. AB - Classical and semiclassical methods are unrivaled in providing an intuitive and computationally tractable approach to the study of atomic, molecular, and nuclear dynamics. An important advantage of such methods is their ability to uncover in a single picture underlying structures that may be hard to extract from the profusion of data supplied by detailed quantum calculations. Modern trends in semiclassical mechanics are described, particularly the combination of group theoretical methods with techniques of nonlinear dynamics. Application is made to intramolecular energy transfer and to the electronic structure of atomic Rydberg states in external electric and magnetic fields. PMID- 17749911 TI - Evolution of pollen morphology. AB - Over evolutionary time, the morphology of angiosperm pollen has evolved toward an increasing number of apertures, among other things. From a neo-Darwinian point of view, this means that (i) some polymorphism for aperture number must exist and (ii) there must be some fitness increase associated with increasing the aperture number. Pollen types with different aperture numbers often occur in the same species. Such is the case in Viola diversifolia. Comparison of pollen with three and four apertures in this species showed that four-apertured grains germinated faster than three-apertured ones but that the four-apertured ones experienced other disadvantages. These results obtained on the gametophyte can be interpreted in terms of strategies of the sporophyte. PMID- 17749912 TI - Elimination of two reef-building hydrocorals following the 1982-83 el nino warming event. AB - One probable extinction and one range reduction of eastern Pacific reef-building hydrocoral (Millepora) species mark the first documented cases of species eliminations resulting from the worldwide 1980s coral reef bleaching events. Two of 12 Panamanian coral species were eliminated suddenly from their former ranges by prolonged high sea temperatures during the 1982-83 El Nino-Southern Oscillation event. Three conditions contributed to their demise: high sensitivity to sea warming, populations confined to a small geographic area, and bathymetric restriction to the euphotic zone (